Increased fibroblast density in actinic cheilitis: association with tryptase-positive mast cells, actinic elastosis and epithelial p53 and COX-2 expression.

PubMed

Rojas, Isolde G; Boza, Yadira V; Spencer, Maria Loreto; Flores, Maritza; Martínez, Alejandra

2012-01-01

Actinic cheilitis (AC) is characterized by epithelial and connective tissue alterations caused by ultraviolet sunlight overexposure known as photodamage. Fibroblasts have been linked to photodamage and tumor progression during skin carcinogenesis; however, their role in early lip carcinogenesis remains unknown. The aim of this study was to assess the density of fibroblasts in AC and normal lip (NL) samples and determine their association with markers of lip photodamage. Fibroblasts, mast cells, p53, COX-2, and elastin were detected in NL (n = 20) and AC (n = 28) biopsies using immunohistochemistry/histochemistry. Mast cell and fibroblast density and epithelial p53 and COX-2 expression scores were then obtained. Elastosis was scored 1-4 according to elastin fiber density and tortuosity. Fibroblasts, mast cells, p53, COX-2, and elastosis were increased in AC as compared to NL (P < 0.001). Multivariate analysis showed an association between fibroblast and mast cell density at the papillary and reticular areas of AC and NL (P < 0.05). Papillary fibroblast density was also associated with epithelial p53 and COX-2 expression (P < 0.05). Increased fibroblast density, both papillary and reticular, was found in the high elastosis group (scores 3-4) as compared to the low elastosis group (scores 1-2) (P < 0.01). Increased reticular mast cell density was detected only in the high elastosis group (P < 0.01). Fibroblasts are increased in AC, and they are associated with mast cell density, epithelial p53 and COX-2 expression, and actinic elastosis. Therefore, fibroblasts may contribute to lip photodamage and could be considered useful markers of early lip carcinogenesis. © 2011 John Wiley & Sons A/S.

Single Marker and Haplotype-Based Association Analysis of Semolina and Pasta Colour in Elite Durum Wheat Breeding Lines Using a High-Density Consensus Map

PubMed Central

Haile, Jemanesh K.; Cory, Aron T.; Clarke, Fran R.; Clarke, John M.; Knox, Ron E.; Pozniak, Curtis J.

2017-01-01

Association mapping is usually performed by testing the correlation between a single marker and phenotypes. However, because patterns of variation within genomes are inherited as blocks, clustering markers into haplotypes for genome-wide scans could be a worthwhile approach to improve statistical power to detect associations. The availability of high-density molecular data allows the possibility to assess the potential of both approaches to identify marker-trait associations in durum wheat. In the present study, we used single marker- and haplotype-based approaches to identify loci associated with semolina and pasta colour in durum wheat, the main objective being to evaluate the potential benefits of haplotype-based analysis for identifying quantitative trait loci. One hundred sixty-nine durum lines were genotyped using the Illumina 90K Infinium iSelect assay, and 12,234 polymorphic single nucleotide polymorphism (SNP) markers were generated and used to assess the population structure and the linkage disequilibrium (LD) patterns. A total of 8,581 SNPs previously localized to a high-density consensus map were clustered into 406 haplotype blocks based on the average LD distance of 5.3 cM. Combining multiple SNPs into haplotype blocks increased the average polymorphism information content (PIC) from 0.27 per SNP to 0.50 per haplotype. The haplotype-based analysis identified 12 loci associated with grain pigment colour traits, including the five loci identified by the single marker-based analysis. Furthermore, the haplotype-based analysis resulted in an increase of the phenotypic variance explained (50.4% on average) and the allelic effect (33.7% on average) when compared to single marker analysis. The presence of multiple allelic combinations within each haplotype locus offers potential for screening the most favorable haplotype series and may facilitate marker-assisted selection of grain pigment colour in durum wheat. These results suggest a benefit of haplotype-based analysis over single marker analysis to detect loci associated with colour traits in durum wheat. PMID:28135299

Exposure to cadmium and persistent organochlorine pollutants and its association with bone mineral density and markers of bone metabolism on postmenopausal women

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rignell-Hydbom, A., E-mail: anna.rignell-hydbom@med.lu.se; Skerfving, S.; Lundh, T.

Environmental contaminants such as cadmium and persistent organochlorine pollutants have been proposed as risk factors of osteoporosis, and women may be at an increased risk. To assess associations between exposure to cadmium and two different POPs (2,2',4,4',5,5'-hexachlorobiphenyl CB-153, 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene p,p'-DDE), on one hand, and bone effects, on the other, in a population-based study among postmenopausal (60-70 years) Swedish women with biobanked blood samples. The study included 908 women and was designed to have a large contrast of bone mineral densities, measured with a single photon absorptiometry technique in the non-dominant forearm. Biochemical markers related to bone metabolism were analyzed inmore » serum. Exposure assessment was based on cadmium concentrations in erythrocytes and serum concentrations of CB-153 and p,p'-DDE. Cadmium was negatively associated with bone mineral density and parathyroid hormone, positively with the marker of bone resorption. However, this association disappeared after adjustment for smoking. The major DDT metabolite (p,p'-DDE) was positively associated with bone mineral density, an association which remained after adjustment for confounders, but the effect was weak. There was no evidence that the estrogenic congener (CB-153) was associated with any of the bone markers. In conclusion, no convincing associations were observed between cadmium and POPs, on one hand, and bone metabolism markers and BMD, on the other.« less

A hospital based study of biochemical markers of bone turnovers & bone mineral density in north Indian women

PubMed Central

Kumar, Ashok; Devi, Salam Gyaneshwori; Mittal, Soniya; Shukla, Deepak Kumar; Sharma, Shashi

2013-01-01

Background & objectives: The osteoporotic risk for women increases soon after menopause. Bone turnover markers are known to be associated with bone loss and fracture risk. This study was aimed to assess bone turnover using bone markers and their correlation with bone mineral density (BMD) in pre- and post-menopausal women. Methods: A total of 255 healthy women (160 pre- and 95 post-menopausal) were enrolled. Serum bone alkaline phosphatase (sBAP) and serum N-terminal telopeptide of type I collagen (NTX) were measured to evaluate the bone formation and resorption, respectively. Bone mineral density was determined at lumbar spine (L2-L4) anteroposteriorly, femoral neck and Ward's triangle using Prodigy dual-energy X-ray absorptiometry (DXA) system. The comparison of years since menopause with respect to BMD and bone markers was also evaluated. Results: NTX and sBAP showed significant negative correlation with BMD of femur neck and Ward's triangle in postmenopausal women. BMD of all three sides were significant variables for NTX and BMD of femur neck and Ward's triangle for sBAP in postmenopausal women. BMD lumbar spine was a significant variable for sBAP in premenopausal women. The mean values of NTX increased significantly with increase in the duration of years since menopause. The BMD of all three sides decreased significantly with increase in the duration of years since menopause. Interpretation & conclusions: Serum NTX and sBAP were inversely correlated to BMD of femur neck and Ward's triangle in post-menopausal women. Simultaneous measurements of NTX and BMD in the north Indian women, suggest that bone resorption in women with low BMD remains high after menopause. PMID:23481051

Temporal and spatial changes of cells positive for stem-like markers in different compartments and stages of human colorectal adenoma-carcinoma sequence

PubMed Central

Cui, Guanglin; Xu, Gang; Zhu, Li; Pang, Zhigang; Zheng, Wei; Li, Zhenfeng; Yuan, Aping

2017-01-01

Considerable evidence supports the idea that stem-like cells may play an essential role during the development of colorectal cancer (CRC). To accomplish this aim, we use immunohistochemistry (IHC) and double IHC with different potential stem-like markers, anti-musashi (Msi), anti-CD133, anti- LGR5 and anti-ALDH1 to examine the presentation of stem-like cells in different compartments including adenoma/CRC epithelium, transitional crypts and tumor stroma in colorectal adenoma and CRC. The results showed that cells positive for stem-like markers were remarkably increased in number and frequently observed in the adenoma/CRC epithelium, transitional crypts and tumor stroma. Notably, the population of cells positive for stem-liker markers was expanded from the base to the middle part of the transitional crypt in both adenoma and CRC tissues, reflecting that stem-like cells are likely involved in the process of colorectal tumorigenesis. Counting results showed that the grading scores of cells positive for LGR5 and ALDH1 in the adenoma/CRC epithelium were significantly increased relative with the control epithelium, and associated with the degree of dysplasia in the adenoma and node involvement in the CRC (all P < 0.05). In addition, the density of cells positive for stem–like markers in the adenomatous/cancerous stroma was also increased and paralleled an increase in the density of proliferative stromal cells labeled by PCNA, which were primarily identified as vimentin positive fibroblasts. Our results have revealed a changed temporal and spatial presentation of stem-like markers in different stages of human colorectal adenoma-carcinoma sequence, which might be a hallmark of the adenoma-carcinoma transition. PMID:28484082

Antibody-immobilized column for quick cell separation based on cell rolling.

PubMed

Mahara, Atsushi; Yamaoka, Tetsuji

2010-01-01

Cell separation using methodological standards that ensure high purity is a very important step in cell transplantation for regenerative medicine and for stem cell research. A separation protocol using magnetic beads has been widely used for cell separation to isolate negative and positive cells. However, not only the surface marker pattern, e.g., negative or positive, but also the density of a cell depends on its developmental stage and differentiation ability. Rapid and label-free separation procedures based on surface marker density are the focus of our interest. In this study, we have successfully developed an antiCD34 antibody-immobilized cell-rolling column, that can separate cells depending on the CD34 density of the cell surfaces. Various conditions for the cell-rolling column were optimized including graft copolymerization, and adjustment of the column tilt angle, and medium flow rate. Using CD34-positive and -negative cell lines, the cell separation potential of the column was established. We observed a difference in the rolling velocities between CD34-positive and CD34-negative cells on antibody-immobilized microfluidic device. Cell separation was achieved by tilting the surface 20 degrees and the increasing medium flow. Surface marker characteristics of the isolated cells in each fraction were analyzed using a cell-sorting system, and it was found that populations containing high density of CD34 were eluted in the delayed fractions. These results demonstrate that cells with a given surface marker density can be continuously separated using the cell rolling column.

A high density physical map of chromosome 1BL supports evolutionary studies, map-based cloning and sequencing in wheat

PubMed Central

2013-01-01

Background As for other major crops, achieving a complete wheat genome sequence is essential for the application of genomics to breeding new and improved varieties. To overcome the complexities of the large, highly repetitive and hexaploid wheat genome, the International Wheat Genome Sequencing Consortium established a chromosome-based strategy that was validated by the construction of the physical map of chromosome 3B. Here, we present improved strategies for the construction of highly integrated and ordered wheat physical maps, using chromosome 1BL as a template, and illustrate their potential for evolutionary studies and map-based cloning. Results Using a combination of novel high throughput marker assays and an assembly program, we developed a high quality physical map representing 93% of wheat chromosome 1BL, anchored and ordered with 5,489 markers including 1,161 genes. Analysis of the gene space organization and evolution revealed that gene distribution and conservation along the chromosome results from the superimposition of the ancestral grass and recent wheat evolutionary patterns, leading to a peak of synteny in the central part of the chromosome arm and an increased density of non-collinear genes towards the telomere. With a density of about 11 markers per Mb, the 1BL physical map provides 916 markers, including 193 genes, for fine mapping the 40 QTLs mapped on this chromosome. Conclusions Here, we demonstrate that high marker density physical maps can be developed in complex genomes such as wheat to accelerate map-based cloning, gain new insights into genome evolution, and provide a foundation for reference sequencing. PMID:23800011

Breast cancer patients with dense breasts do not have increased death risk

Cancer.gov

High mammographic breast density, which is a marker of increased risk of developing breast cancer, does not seem to increase the risk of death among breast cancer patients, according to a study led by Gretchen L. Gierach, Ph.D., NCI. Image shows physician

Diurnal Variation of Hormonal and Lipid Biomarkers in a Molecular Epidemiology-Like Setting.

PubMed

van Kerkhof, Linda W M; Van Dycke, Kirsten C G; Jansen, Eugene H J M; Beekhof, Piet K; van Oostrom, Conny T M; Ruskovska, Tatjana; Velickova, Nevenka; Kamcev, Nikola; Pennings, Jeroen L A; van Steeg, Harry; Rodenburg, Wendy

2015-01-01

Many molecular epidemiology studies focusing on high prevalent diseases, such as metabolic disorders and cancer, investigate metabolic and hormonal markers. In general, sampling for these markers can occur at any time-point during the day or after an overnight fast. However, environmental factors, such as light exposure and food intake might affect the levels of these markers, since they provide input for the internal time-keeping system. When diurnal variation is larger than the inter-individual variation, time of day should be taken into account. Importantly, heterogeneity in diurnal variation and disturbance of circadian rhythms among a study population might increasingly occur as a result of our increasing 24/7 economy and related variation in exposure to environmental factors (such as light and food). The aim of the present study was to determine whether a set of often used biomarkers shows diurnal variation in a setting resembling large molecular epidemiology studies, i.e., non-fasted and limited control possibilities for other environmental influences. We show that markers for which diurnal variation is not an issue are adrenocorticotropic hormone, follicle stimulating hormone, estradiol and high-density lipoprotein. For all other tested markers diurnal variation was observed in at least one gender (cholesterol, cortisol, dehydroepiandrosterone sulfate, free fatty acids, low-density lipoprotein, luteinizing hormone, prolactin, progesterone, testosterone, triglycerides, total triiodothyronine and thyroid-stimulating hormone) or could not reliably be detected (human growth hormone). Thus, studies investigating these markers should take diurnal variation into account, for which we provide some options. Furthermore, our study indicates the need for investigating diurnal variation (in literature or experimentally) before setting up studies measuring markers in routine and controlled settings, especially since time-of-day likely matters for many more markers than the ones investigated in the present study.

Correlations between female breast density and biochemical markers.

PubMed

Kim, Ji-Hye; Lee, Hae-Kag; Cho, Jae-Hwan; Park, Hyong-Keun; Yang, Han-Jun

2015-07-01

[Purpose] The aim of this study was to identify biochemical markers related to breast density. The study was performed with 200 patients who received mammography and biochemical marker testing between March 1, 2014 to October 1, 2014. [Subjects and Methods] Following the American College of Radiology, Breast Imaging Reporting and Data System (ACR BI-RADS), breast parenchymal pattern density from mammography was categorized into four grades: grade 1, almost entirely fat; grade 2, fibroglandular densities; grade 3, heterogeneously dense; and grade 4, extremely dense. Regarding biochemical markers, subjects underwent blood and urine tests after a 12-h fast. We analyzed correlations among breast density, general characteristics, and biochemical markers. [Results] Breast density-related factors were age, height, weight, body mass index (BMI), hematocrit, MCH, RDW, AST, ALT, ALP, uric acid, γGT, triglycerides, total cholesterol, HDL-cholesterol, and LDL-cholesterol. [Conclusion] The results can be used as basic and comparative data for the prevention and early control of breast cancer.

The effects of phytoestrogen isoflavones on bone density in women: a double-blind, randomized, placebo-controlled trial.

PubMed

Atkinson, Charlotte; Compston, Juliet E; Day, Nicholas E; Dowsett, Mitch; Bingham, Sheila A

2004-02-01

Isoflavone phytoestrogen therapy has been proposed as a natural alternative to hormone replacement therapy (HRT). HRT has a beneficial effect on bone, but few trials in humans have investigated the effects of isoflavones on bone. The objective of the study was to determine the effect on bone density of a red clover-derived isoflavone supplement that provided a daily dose of 26 mg biochanin A, 16 mg formononetin, 1 mg genistein, and 0.5 mg daidzein for 1 y. Effects on biochemical markers of bone turnover and body composition were also studied. Women aged 49-65 y (n = 205) were enrolled in a double-blind, randomized, placebo-controlled trial; 177 completed the trial. Bone density, body composition, bone turnover markers, and diet were measured at baseline and after 12 mo. Loss of lumbar spine bone mineral content and bone mineral density was significantly (P = 0.04 and P = 0.03, respectively) lower in the women taking the isoflavone supplement than in those taking the placebo. There were no significant treatment effects on hip bone mineral content or bone mineral density, markers of bone resorption, or body composition, but bone formation markers were significantly increased (P = 0.04 and P = 0.01 for bone-specific alkaline phosphatase and N-propeptide of collagen type I, respectively) in the intervention group compared with placebo in postmenopausal women. Interactions between treatment group and menopausal status with respect to changes in other outcomes were not significant. These data suggest that, through attenuation of bone loss, isoflavones have a potentially protective effect on the lumbar spine in women.

CPB-K mice a mouse model of schizophrenia? Differences in dopaminergic, serotonergic and behavioral markers compared to BALB/cJ mice.

PubMed

Panther, P; Nullmeier, S; Dobrowolny, H; Schwegler, H; Wolf, R

2012-04-21

Schizophrenia is characterized by disturbances in social behavior, sensorimotor gating and cognitive function, that are discussed to be caused by a termination of different transmitter systems. Beside morphological alterations in cortical and subcortical areas reduced AMPA- NMDA-, 5-HT2-receptor densities and increased 5-HT1-receptor densities are found in the hippocampus.The two inbred mouse strains CPB-K and BALB/cJ are known to display considerable differences in cognitive function and prepulse inhibition, a stable marker of sensorimotor gating. Furthermore, CPB-K mice exhibit lower NMDA-, AMPA- and increased 5-HT-receptor densities in the hippocampus as compared to BALB/cJ mice. We investigated both mouse strains in social interaction test for differences in social behavior and with immuncytochemical approaches for alterations of dopaminergic and serotonergic parameters. Our results can be summarized as follows: compared to BALB/cJ, CPB-K mice showed:(1) significantly reduced traveling distance and number of contacts in social interaction test, (2) differences in the number of serotonin transporter-immunoreactive neurons and volume of raphe nuclei and a lower serotonergic fiber density in the ventral and dorsal hippocampal subfields CA1 and CA3, (3) no alterations of dopaminergic markers like neuron number, neuron density and volume in subregions of substantia nigra and ventral tegmental area, but a significantly higher dopaminergic fiber density in the dorsal hippocampus, the ventral hippocampus of CA1 and gyrus dentatus, (4) no significant differences in serotonergic and dopaminergic fiber densities in the amygdala.Based on our results and previous studies, CPB-K mice compared to BALB/cJ may serve as an important model to understand the interaction of the serotonergic and dopaminergic system and their impact on sensorimotor gating and cognitive function as related to neuropsychiatric disorders like schizophrenia. 2012 Elsevier B.V. All rights reserved.

Myocardial potency of Bio-tea against Isoproterenol induced myocardial damage in rats.

PubMed

Lobo, Reema Orison; Shenoy, Chandrakala K

2015-07-01

Kombucha (Bio-tea) is a beverage produced by the fermentation of sugared black tea using a symbiotic association of bacteria and yeasts. Traditional claims about Kombucha report beneficial effects such as antibiotic properties, gastric regulation, relief from joint rheumatism and positive influence on the cholesterol level, arteriosclerosis, diabetes, and aging problems. The present investigation was carried out to understand the preventive effect of Kombucha on heart weight, blood glucose, total protein, lipid profile and cardiac markers in rats with myocardial damage induced using Isoproterenol. As Bio-tea is produced by fermenting tea, the parameters were compared in rats pre-treated with normal black tea and Bio-tea for 30 days followed by subcutaneous injection of Isoproterenol (85 mg/kg body weight). Normal rats as well as Isoproterenol induced myocardial infarcted rats were also used, which served as controls. Isoproterenol induced myocardial infarcted control rats showed a significant increase in heart weight, blood glucose and cardiac markers and a decrease in plasma protein. Increased levels of cholesterol, triglycerides, low density lipids (LDL) and very low density lipids (VLDL) were also observed, while the high density lipid (HDL) content decreased. Bio-tea showed a higher preventive effect against myocardial infarction when compared to tea, as was observed by the significant reduction in heart weight, and blood glucose and increase in plasma albumin levels. Bio-tea significantly decreased cholesterol, triglycerides, LDL and VLDL while simultaneously increasing the levels of HDL. Similarly a decrease in leakage of cardiac markers from the myocardium was also observed.

High-density marker imputation accuracy in sixteen French cattle breeds.

PubMed

Hozé, Chris; Fouilloux, Marie-Noëlle; Venot, Eric; Guillaume, François; Dassonneville, Romain; Fritz, Sébastien; Ducrocq, Vincent; Phocas, Florence; Boichard, Didier; Croiseau, Pascal

2013-09-03

Genotyping with the medium-density Bovine SNP50 BeadChip® (50K) is now standard in cattle. The high-density BovineHD BeadChip®, which contains 777,609 single nucleotide polymorphisms (SNPs), was developed in 2010. Increasing marker density increases the level of linkage disequilibrium between quantitative trait loci (QTL) and SNPs and the accuracy of QTL localization and genomic selection. However, re-genotyping all animals with the high-density chip is not economically feasible. An alternative strategy is to genotype part of the animals with the high-density chip and to impute high-density genotypes for animals already genotyped with the 50K chip. Thus, it is necessary to investigate the error rate when imputing from the 50K to the high-density chip. Five thousand one hundred and fifty three animals from 16 breeds (89 to 788 per breed) were genotyped with the high-density chip. Imputation error rates from the 50K to the high-density chip were computed for each breed with a validation set that included the 20% youngest animals. Marker genotypes were masked for animals in the validation population in order to mimic 50K genotypes. Imputation was carried out using the Beagle 3.3.0 software. Mean allele imputation error rates ranged from 0.31% to 2.41% depending on the breed. In total, 1980 SNPs had high imputation error rates in several breeds, which is probably due to genome assembly errors, and we recommend to discard these in future studies. Differences in imputation accuracy between breeds were related to the high-density-genotyped sample size and to the genetic relationship between reference and validation populations, whereas differences in effective population size and level of linkage disequilibrium showed limited effects. Accordingly, imputation accuracy was higher in breeds with large populations and in dairy breeds than in beef breeds. More than 99% of the alleles were correctly imputed if more than 300 animals were genotyped at high-density. No improvement was observed when multi-breed imputation was performed. In all breeds, imputation accuracy was higher than 97%, which indicates that imputation to the high-density chip was accurate. Imputation accuracy depends mainly on the size of the reference population and the relationship between reference and target populations.

High-density marker imputation accuracy in sixteen French cattle breeds

PubMed Central

2013-01-01

Background Genotyping with the medium-density Bovine SNP50 BeadChip® (50K) is now standard in cattle. The high-density BovineHD BeadChip®, which contains 777 609 single nucleotide polymorphisms (SNPs), was developed in 2010. Increasing marker density increases the level of linkage disequilibrium between quantitative trait loci (QTL) and SNPs and the accuracy of QTL localization and genomic selection. However, re-genotyping all animals with the high-density chip is not economically feasible. An alternative strategy is to genotype part of the animals with the high-density chip and to impute high-density genotypes for animals already genotyped with the 50K chip. Thus, it is necessary to investigate the error rate when imputing from the 50K to the high-density chip. Methods Five thousand one hundred and fifty three animals from 16 breeds (89 to 788 per breed) were genotyped with the high-density chip. Imputation error rates from the 50K to the high-density chip were computed for each breed with a validation set that included the 20% youngest animals. Marker genotypes were masked for animals in the validation population in order to mimic 50K genotypes. Imputation was carried out using the Beagle 3.3.0 software. Results Mean allele imputation error rates ranged from 0.31% to 2.41% depending on the breed. In total, 1980 SNPs had high imputation error rates in several breeds, which is probably due to genome assembly errors, and we recommend to discard these in future studies. Differences in imputation accuracy between breeds were related to the high-density-genotyped sample size and to the genetic relationship between reference and validation populations, whereas differences in effective population size and level of linkage disequilibrium showed limited effects. Accordingly, imputation accuracy was higher in breeds with large populations and in dairy breeds than in beef breeds. More than 99% of the alleles were correctly imputed if more than 300 animals were genotyped at high-density. No improvement was observed when multi-breed imputation was performed. Conclusion In all breeds, imputation accuracy was higher than 97%, which indicates that imputation to the high-density chip was accurate. Imputation accuracy depends mainly on the size of the reference population and the relationship between reference and target populations. PMID:24004563

A High Density Consensus Map of Rye (Secale cereale L.) Based on DArT Markers

PubMed Central

Myśków, Beata; Stojałowski, Stefan; Heller-Uszyńska, Katarzyna; Góralska, Magdalena; Brągoszewski, Piotr; Uszyński, Grzegorz; Kilian, Andrzej; Rakoczy-Trojanowska, Monika

2011-01-01

Background Rye (Secale cereale L.) is an economically important crop, exhibiting unique features such as outstanding resistance to biotic and abiotic stresses and high nutrient use efficiency. This species presents a challenge to geneticists and breeders due to its large genome containing a high proportion of repetitive sequences, self incompatibility, severe inbreeding depression and tissue culture recalcitrance. The genomic resources currently available for rye are underdeveloped in comparison with other crops of similar economic importance. The aim of this study was to create a highly saturated, multilocus linkage map of rye via consensus mapping, based on Diversity Arrays Technology (DArT) markers. Methodology/Principal Findings Recombinant inbred lines (RILs) from 5 populations (564 in total) were genotyped using DArT markers and subjected to linkage analysis using Join Map 4.0 and Multipoint Consensus 2.2 software. A consensus map was constructed using a total of 9703 segregating markers. The average chromosome map length ranged from 199.9 cM (2R) to 251.4 cM (4R) and the average map density was 1.1 cM. The integrated map comprised 4048 loci with the number of markers per chromosome ranging from 454 for 7R to 805 for 4R. In comparison with previously published studies on rye, this represents an eight-fold increase in the number of loci placed on a consensus map and a more than two-fold increase in the number of genetically mapped DArT markers. Conclusions/Significance Through the careful choice of marker type, mapping populations and the use of software packages implementing powerful algorithms for map order optimization, we produced a valuable resource for rye and triticale genomics and breeding, which provides an excellent starting point for more in-depth studies on rye genome organization. PMID:22163026

Are breast density and bone mineral density independent risk factors for breast cancer?

PubMed

Kerlikowske, Karla; Shepherd, John; Creasman, Jennifer; Tice, Jeffrey A; Ziv, Elad; Cummings, Steve R

2005-03-02

Mammographic breast density and bone mineral density (BMD) are markers of cumulative exposure to estrogen. Previous studies have suggested that women with high mammographic breast density or high BMD are at increased risk of breast cancer. We determined whether mammographic breast density and BMD of the hip and spine are correlated and independently associated with breast cancer risk. We conducted a cross-sectional study (N = 15,254) and a nested case-control study (of 208 women with breast cancer and 436 control subjects) among women aged 28 years or older who had a screening mammography examination and hip BMD measurement within 2 years. Breast density for 3105 of the women was classified using the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) categories, and percentage mammographic breast density among the case patients and control subjects was quantified with a computer-based threshold method. Spearman rank partial correlation coefficient and Pearson's correlation coefficient were used to examine correlations between BI-RADS breast density and BMD and between percentage mammographic breast density and BMD, respectively, in women without breast cancer. Logistic regression was used to examine the association of breast cancer with percentage mammographic breast density and BMD. All statistical tests were two-sided. Neither BI-RADS breast density nor percentage breast density was correlated with hip or spine BMD (correlation coefficient = -.02 and -.01 for BI-RADS, respectively, and -.06 and .01 for percentage breast density, respectively). Neither hip BMD nor spine BMD had a statistically significant relationship with breast cancer risk. Women with breast density in the highest sextile had an approximately threefold increased risk of breast cancer compared with women in the lowest sextile (odds ratio = 2.7, 95% confidence interval = 1.4 to 5.4); adjusting for hip or spine BMD did not change the association between breast density and breast cancer risk. Breast density is strongly associated with increased risk of breast cancer, even after taking into account reproductive and hormonal risk factors, whereas BMD, although a possible marker of lifetime exposure to estrogen, is not. Thus, a component of breast density that is independent of estrogen-mediated effects may contribute to breast cancer risk.

VEGF165 Stimulates Vessel Density and Vessel Diameter Differently in Angiogenesis and Lymphangiogenesis

NASA Technical Reports Server (NTRS)

Parsons-Wingerter, Patricia; Radhakrishnan, Krishnan; DiCorleto, Paul E.; Leontiev, Dmitry; Anand-Apte, Bela; Albarran, Brian; Farr, Andrew G.

2005-01-01

Vascular endothelial growth factor-165 (VEGF(sub 165)) stimulated angiogenesis in the quail chorioallantoic membrane (CAM) by vessel expansion from the capillary network. However, lymphangiogenesis was stimulated by the filopodial guidance of tip cells located on blind-ended lymphatic sprouts. As quantified by fractal/generational branching analysis using the computer code VESGEN, vascular density increased maximally at low VEGF concentrations, and vascular diameter increased most at high VEGF concentrations. Increased vascular density and diameter were statistically independent events (r(sub s), -0.06). By fluorescence immunohistochemistry of VEGF receptors VEGFR-1 and VEGFR-2, alpha smooth muscle actin ((alpha) SMA) and a vascular/lymphatic marker, VEGF(sub 165) increased the density and diameter of sprouting lymphatic vessels guided by tip cells (accompanied by the dissociation of lymphatics from blood vessels). Isolated migratory cells expressing (alpha)SMA were recruited to blood vessels, whereas isolated cells expressing VEGFR-2 were recruited primarily to lymphatics. In conclusion, VEGF(sub 165) increased lymphatic vessel density by lymphatic sprouting, but increased blood vessel density by vascular expansion from the capillary network.

Analysis of Pediatric Waist to Hip Ratio Relationship to Metabolic Syndrome Markers.

PubMed

Moore, Lindy M; Fals, Angela M; Jennelle, Pamela J; Green, Jeanette F; Pepe, Julie; Richard, Tere

2015-01-01

Waist to hip ratio (WHR) is a valid assessment tool to determine risk for the development or presence of metabolic syndrome, diabetes, and cardiovascular disease in adults. Evidence-based research on its validity with children and adolescents is limited. A retrospective analysis was conducted to determine if WHR in overweight and obese pediatric patients is associated with metabolic syndrome laboratory markers. Retrospective chart reviews were performed for 754 patients ages 6 to 17 years who were enrolled in a weight management program. Data collected included WHR, laboratory markers for metabolic disorder, body mass index, demographics, presence of acanthosis nigricans, and Tanner stage. WHR and high-density lipoprotein were negatively correlated, r (N = 597) = -0.20, p < .001. WHR and triglycerides were positively correlated, r (N = 597) = 0.19, p < .001, as were WHR and low-density lipoprotein, r (N = 596) = 0.09, p = .03, and WHR and insulin, r (N = 414) = 0.16, p = .001. In a subject sample with very restricted range, a one-way analysis of variance found a significant effect of WHR on body mass index percentile, F (1, 754) = 22.43, p < .001, η(2) = 0.03. Increased WHR correlated in children and adolescents with known indicators that could be suggestive of increased risk for metabolic syndrome, specifically low high-density lipoprotein, high low-density lipoprotein, triglycerides, and insulin. These results suggest that evaluation of WHR may be a useful tool to indicate risk for developing metabolic syndrome and diabetes in children and adolescents. Copyright © 2015 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.

[Clinical usefulness of bone turnover markers in the management of osteoporosis].

PubMed

Yano, Shozo

2013-09-01

Osteoporosis is a state of elevated risk for bone fracture due to depressed bone strength, which is considered to be the sum of bone mineral density and bone quality. Since a measure of bone quality has not been established, bone mineral density and bone turnover markers are the only way to evaluate bone strength. Bone turnover markers are classified into bone formation marker and resorption marker, which are correlated with the bone formation rate and resorption rate, respectively, and bone matrix-related marker. Bone is always metabolized; old tissue is resorbed by acids and proteases derived from osteoclasts, whereas new bone is produced by osteoblasts. Bone formation and resorption rates should be balanced (also called coupled). When the bone resorption rate exceeds the formation rate(uncoupled state), bone volume will be reduced. Thus, we can comprehend bone metabolism by measuring both formation and resorption markers at the same time. Increased fracture risk is recognized by elevated bone resorption markers and undercarboxylated osteocalcin, which reflects vitamin K insufficiency and bone turnover. These values and the time course give us helpful information to choose medicine suitable for the patients and to judge the responsiveness. If the value is extraordinarily high without renal failure, metabolic bone disorder or bone metastatic tumor should be considered. Bone quality may be assessed by measuring bone matrix-related markers such as homocystein and pentosidine. Since recent studies indicate that the bone is a hormone-producing organ, it is possible that glucose metabolism or an unknown mechanism could be assessed in the future.

Bone Metabolism in Adolescent Athletes With Amenorrhea, Athletes With Eumenorrhea, and Control Subjects

PubMed Central

Christo, Karla; Prabhakaran, Rajani; Lamparello, Brooke; Cord, Jennalee; Miller, Karen K.; Goldstein, Mark A.; Gupta, Nupur; Herzog, David B.; Klibanski, Anne; Misra, Madhusmita

2011-01-01

OBJECTIVE We hypothesized that, despite increased activity, bone density would be low in athletes with amenorrhea, compared with athletes with eumenorrhea and control subjects, because of associated hypogonadism and would be associated with a decrease in bone formation and increases in bone-resorption markers. METHODS In a cross-sectional study, we examined bone-density measures (spine, hip, and whole body) and body composition by using dual-energy radiograph absorptiometry and assessed fasting levels of insulin-like growth factor I and bone-turnover markers (N-terminal propeptied of type 1 procollagen and N-telopeptide) in 21 athletes with amenorrhea, 18 athletes with eumenorrhea, and 18 control subjects. Subjects were 12 to 18 years of age and of comparable chronologic and bone age. RESULTS Athletes with amenorrhea had lower bone-density z scores at the spine and whole body, compared with athletes with eumenorrhea and control subjects, and lower hip z scores, compared with athletes with eumenorrhea. Lean mass did not differ between groups. However, athletes with amenorrhea had lower BMI z scores than did athletes with eumenorrhea and lower insulin-like growth factor I levels than did control subjects. Levels of both markers of bone turnover were lower in athletes with amenorrhea than in control subjects. BMI z scores, lean mass, insulin-like growth factor I levels, and diagnostic category were important independent predictors of bone mineral density z scores. CONCLUSIONS Although they showed no significant differences in lean mass, compared with athletes with eumenorrhea and control subjects, athletes with amenorrhea had lower bone density at the spine and whole body. Insulin-like growth factor I levels, body-composition parameters, and menstrual status were important predictors of bone density. Follow-up studies are necessary to determine whether amenorrhea in athletes adversely affects the rate of bone mass accrual and therefore peak bone mass. PMID:18519482

Pneumococcal colonisation density: a new marker for disease severity in HIV-infected adults with pneumonia

PubMed Central

Albrich, Werner C; Madhi, Shabir A; Adrian, Peter V; van Niekerk, Nadia; Telles, Jean-Noel; Ebrahim, N; Messaoudi, Melina; Paranhos-Baccalà, Glaucia; Giersdorf, Sven; Vernet, Guy; Mueller, Beat; Klugman, Keith P

2014-01-01

Objective A high genomic load of Pneumococcus from blood or cerebrospinal fluid has been associated with increased mortality. We aimed to analyse whether nasopharyngeal colonisation density in HIV-infected patients with community-acquired pneumonia (CAP) is associated with markers of disease severity or poor outcome. Methods Quantitative lytA real-time PCR was performed on nasopharyngeal swabs in HIV-infected South African adults hospitalised for acute CAP at Chris Hani Baragwanath Hospital, Soweto, South Africa. Pneumonia aetiology was considered pneumococcal if any sputum culture or Gram stain, urinary pneumococcal C-polysaccharide-based antigen, blood culture or whole blood lytA real-time PCR revealed pneumococci. Results There was a moderate correlation between the mean nasopharyngeal colonisation densities and increasing CURB65 scores among all-cause patients with pneumonia (Spearman correlation coefficient r=0.15, p=0.06) or with the Pitt bacteraemia score among patients with pneumococcal bacteraemia (p=0.63). In patients with pneumococcal pneumonia, nasopharyngeal pneumococcal colonisation density was higher among non-survivors than survivors (7.7 vs 6.1 log10 copies/mL, respectively, p=0.02) and among those who had pneumococci identified from blood cultures and/or by whole blood lytA real-time PCR than those with non-bacteraemic pneumococcal pneumonia (6.6 vs 5.6 log10 copies/mL, p=0.03). Nasopharyngeal colonisation density correlated positively with the biomarkers procalcitonin (Spearman correlation coefficient r=0.37, p<0.0001), proadrenomedullin (r=0.39, p=0.008) and copeptin (r=0.30, p=0.01). Conclusions In addition to its previously reported role as a diagnostic tool for pneumococcal pneumonia, quantitative nasopharyngeal colonisation density also correlates with mortality and prognostic biomarkers. It may also be useful as a severity marker for pneumococcal pneumonia in HIV-infected adults. PMID:25113557

Dating of Traumatic Brain Injury in Forensic Cases Using Immunohistochemical Markers (I): Neurofilaments and β-Amyloid Precursor Protein.

PubMed

Romero Tirado, María de Los Ángeles; Blanco Pampin, José Manuel; Gallego Gómez, Rosalía

2018-06-13

Studies about head trauma are experimental or have a clinical or prognosis purpose. In this study, we used samples from human autopsies to answer common medical-legal questions.We studied 21 problem cases and 4 controls. Samples were obtained directly from the injured area, fixed in 10% formalin during 24 hours and then preserved in 70% ethanol. This procedure optimizes the immunohistochemical technique.The neurofilament antibody shows beaded axons since the first moment; over time, they increase their density and diameter as survival time also increases. These changes begin in the gray matter, 2 hours after trauma can be seen around vessels and in hemorrhagic areas. At 24 hours, beaded axons appear in the white mater, which finally loses its structure and cellular density.On the other hand, the β-amyloid precursor protein marker begins to be weakly seen 2 hours after injury. At 24 hours, a diffuse pattern can appear, suggesting primary traumatic injury. The marker reading keeps increasing until day 26, when a "Z" pattern appears in the white matter, suggesting secondary hypoxic injury.All these chronologic changes could be useful to approach the date of trauma. They let us to distinguish between long surviving cases from those whose death was immediate (within the first 30 minutes).

PCOS is associated with increased CD11c expression and crown-like structures in adipose tissue and increased central abdominal fat depots independent of obesity.

PubMed

Huang, Zhi Hua; Manickam, Buvana; Ryvkin, Victoria; Zhou, Xiaohong Joe; Fantuzzi, Giamila; Mazzone, Theodore; Sam, Susan

2013-01-01

Adipose tissue macrophage (ATM) infiltration is a major pathway for obesity-induced insulin resistance but has not been studied as a mechanism for insulin resistance in PCOS. We tested whether polycystic ovary syndrome (PCOS) is associated with increased ATM infiltration, especially of inflammatory subtype identified by the CD11c marker. We conducted a case-control study at an academic medical center in the United States. Fourteen PCOS and 14 control women of similar age and body mass index (BMI) underwent a gluteal fat biopsy. Markers of ATM, integrins, TNF-α, and adiponectin, were analyzed by quantitative RT-PCR using a standard curve method. Crown-like structures (CLS) were identified by immunohistochemistry. Abdominal magnetic resonance imaging and frequently sampled i.v. glucose tolerance test were performed to assess abdominal fat and insulin sensitivity (SI). Women with PCOS were compared with control women of similar age and BMI for ATM markers, CLS density, adipose tissue expression of inflammatory cytokines and adiponectin, SI, and abdominal fat depots. Women with PCOS had an increase in CD11c expression (P = 0.03), CLS density (P = 0.001), α5 expression (P = 0.009), borderline increase in TNF-α expression (P = 0.08), and a decrease in adiponectin expression (P = 0.02) in gluteal adipose tissue. Visceral (P = 0.009) and sc abdominal fat (P = 0.005) were increased in PCOS. SI was lower in PCOS (P = 0.008). PCOS is associated with an increase in CD11c expression and CLS density and a decrease in adiponectin expression in sc adipose tissue. Additionally, PCOS is associated with higher central abdominal fat depots independent of BMI. These alterations are present among mostly nonobese women and could represent mechanisms for insulin resistance.

Unlocking Diversity in Germplasm Collections via Genomic Selection: A Case Study Based on Quantitative Adult Plant Resistance to Stripe Rust in Spring Wheat.

PubMed

Muleta, Kebede T; Bulli, Peter; Zhang, Zhiwu; Chen, Xianming; Pumphrey, Michael

2017-11-01

Harnessing diversity from germplasm collections is more feasible today because of the development of lower-cost and higher-throughput genotyping methods. However, the cost of phenotyping is still generally high, so efficient methods of sampling and exploiting useful diversity are needed. Genomic selection (GS) has the potential to enhance the use of desirable genetic variation in germplasm collections through predicting the genomic estimated breeding values (GEBVs) for all traits that have been measured. Here, we evaluated the effects of various scenarios of population genetic properties and marker density on the accuracy of GEBVs in the context of applying GS for wheat ( L.) germplasm use. Empirical data for adult plant resistance to stripe rust ( f. sp. ) collected on 1163 spring wheat accessions and genotypic data based on the wheat 9K single nucleotide polymorphism (SNP) iSelect assay were used for various genomic prediction tests. Unsurprisingly, the results of the cross-validation tests demonstrated that prediction accuracy increased with an increase in training population size and marker density. It was evident that using all the available markers (5619) was unnecessary for capturing the trait variation in the germplasm collection, with no further gain in prediction accuracy beyond 1 SNP per 3.2 cM (∼1850 markers), which is close to the linkage disequilibrium decay rate in this population. Collectively, our results suggest that larger germplasm collections may be efficiently sampled via lower-density genotyping methods, whereas genetic relationships between the training and validation populations remain critical when exploiting GS to select from germplasm collections. Copyright © 2017 Crop Science Society of America.

Cross-Translational Studies in Human and Drosophila Identify Markers of Sleep Loss

PubMed Central

Thimgan, Matthew S.; Gottschalk, Laura; Toedebusch, Cristina; McLeland, Jennifer; Rechtschaffen, Allan; Gilliland-Roberts, Marcia; Duntley, Stephen P.; Shaw, Paul J.

2013-01-01

Inadequate sleep has become endemic, which imposes a substantial burden for public health and safety. At present, there are no objective tests to determine if an individual has gone without sleep for an extended period of time. Here we describe a novel approach that takes advantage of the evolutionary conservation of sleep to identify markers of sleep loss. To begin, we demonstrate that IL-6 is increased in rats following chronic total sleep deprivation and in humans following 30 h of waking. Discovery experiments were then conducted on saliva taken from sleep-deprived human subjects to identify candidate markers. Given the relationship between sleep and immunity, we used Human Inflammation Low Density Arrays to screen saliva for novel markers of sleep deprivation. Integrin αM (ITGAM) and Anaxin A3 (AnxA3) were significantly elevated following 30 h of sleep loss. To confirm these results, we used QPCR to evaluate ITGAM and AnxA3 in independent samples collected after 24 h of waking; both transcripts were increased. The behavior of these markers was then evaluated further using the power of Drosophila genetics as a cost-effective means to determine whether the marker is associated with vulnerability to sleep loss or other confounding factors (e.g., stress). Transcript profiling in flies indicated that the Drosophila homologues of ITGAM were not predictive of sleep loss. Thus, we examined transcript levels of additional members of the integrin family in flies. Only transcript levels of scab, the Drosophila homologue of Integrin α5 (ITGA5), were associated with vulnerability to extended waking. Since ITGA5 was not included on the Low Density Array, we returned to human samples and found that ITGA5 transcript levels were increased following sleep deprivation. These cross-translational data indicate that fly and human discovery experiments are mutually reinforcing and can be used interchangeably to identify candidate biomarkers of sleep loss. PMID:23637783

Applying a new mammographic imaging marker to predict breast cancer risk

NASA Astrophysics Data System (ADS)

Aghaei, Faranak; Danala, Gopichandh; Hollingsworth, Alan B.; Stoug, Rebecca G.; Pearce, Melanie; Liu, Hong; Zheng, Bin

2018-02-01

Identifying and developing new mammographic imaging markers to assist prediction of breast cancer risk has been attracting extensive research interest recently. Although mammographic density is considered an important breast cancer risk, its discriminatory power is lower for predicting short-term breast cancer risk, which is a prerequisite to establish a more effective personalized breast cancer screening paradigm. In this study, we presented a new interactive computer-aided detection (CAD) scheme to generate a new quantitative mammographic imaging marker based on the bilateral mammographic tissue density asymmetry to predict risk of cancer detection in the next subsequent mammography screening. An image database involving 1,397 women was retrospectively assembled and tested. Each woman had two digital mammography screenings namely, the "current" and "prior" screenings with a time interval from 365 to 600 days. All "prior" images were originally interpreted negative. In "current" screenings, these cases were divided into 3 groups, which include 402 positive, 643 negative, and 352 biopsy-proved benign cases, respectively. There is no significant difference of BIRADS based mammographic density ratings between 3 case groups (p < 0.6). When applying the CAD-generated imaging marker or risk model to classify between 402 positive and 643 negative cases using "prior" negative mammograms, the area under a ROC curve is 0.70+/-0.02 and the adjusted odds ratios show an increasing trend from 1.0 to 8.13 to predict the risk of cancer detection in the "current" screening. Study demonstrated that this new imaging marker had potential to yield significantly higher discriminatory power to predict short-term breast cancer risk.

Prenatal fat exposure and hypothalamic PPAR β/δ: Possible relationship to increased neurogenesis of orexigenic peptide neurons

PubMed Central

Chang, G.-Q.; Karatayev, O.; Lukatskaya, O.; Leibowitz, S. F.

2016-01-01

Gestational exposure to a fat-rich diet, while elevating maternal circulating fatty acids, increases in the offspring's hypothalamus and amygdala the proliferation and density of neurons that express neuropeptides known to stimulate consummatory behavior. To understand the relationship between these phenomena, this study examined in the brain of postnatal offspring (day 15) the effect of prenatal fat exposure on the transcription factor, peroxisome proliferator-activated receptor (PPAR) β/δ, which is sensitive to fatty acids, and the relationship of PPAR β/δ to the orexigenic neuropeptides, orexin, melanin-concentrating hormone, and enkephalin. Prenatal exposure to a fat-rich diet compared to low-fat chow increased the density of cells immunoreactive for PPAR β/δ in the hypothalamic paraventricular nucleus (PVN), perifornical lateral hypothalamus (PFLH), and central nucleus of the amygdala (CeA), but not the hypothalamic arcuate nucleus or basolateral amygdaloid nucleus. It also increased co-labeling of PPAR β/δ with the cell proliferation marker, BrdU, or neuronal marker, NeuN, and the triple labeling of PPAR β/δ with BrdU plus NeuN, indicating an increase in proliferation and density of new PPAR β/δ neurons. Prenatal fat exposure stimulated the double-labeling of PPAR β/δ with orexin or melanin-concentrating hormone in the PFLH and enkephalin in the PVN and CeA and also triple-labeling of PPAR β/δ with BrdU and these neuropeptides, indicating that dietary fat increases the genesis of PPAR β/δ neurons that produce these peptides. These findings demonstrate a close anatomical relationship between PPAR β/δ and the increased proliferation and density of peptide-expressing neurons in the hypothalamus and amygdala of fat-exposed offspring. PMID:27002387

Relationship between serum leptin concentrations and bone mineral density as well as biochemical markers of bone turnover in women with postmenopausal osteoporosis.

PubMed

Shaarawy, Mohamed; Abassi, Asmaa Farid; Hassan, Hany; Salem, Mahmoud E

2003-04-01

To determine whether leptin is involved in bone remodeling in patients with postmenopausal osteoporosis. Cross-sectional study. Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University. Ninety postmenopausal osteoporotic women (37 obese and 53 nonobese) and 30 healthy premenopausal women from the same clinic served as controls. Lumbar spine bone mineral density (LS-BMD) of osteoporotic patients was more than 2.5 SD below the normal mean of healthy premenopausal women. Serum levels of leptin, osteocalcin (OC), bone alkaline phosphatase (B-ALP), urinary deoxypyridinoline (DPyr), and N-telopeptide of type 1 collagen (NTX) as well as LS-BMD using dual energy X-ray absorptiometry (DEXA). The serum leptin level in obese postmenopausal osteoporotic patients was significantly increased compared with nonobese osteoporotic patients. There were no significant differences of bone formation markers (B-ALP, OC), bone resorption markers (DPyr, NTX), or LS-BMD between the obese and nonobese groups. There were no significant correlations between serum leptin and any biomarkers of bone turnover and BMD. In postmenopausal osteoporotic patients with increased bone turnover, serum leptin concentration is not correlated with BMD or with the biomarkers of bone formation or bone resorption.

Stereotactic core needle breast biopsy marker migration: An analysis of factors contributing to immediate marker migration.

PubMed

Jain, Ashali; Khalid, Maria; Qureshi, Muhammad M; Georgian-Smith, Dianne; Kaplan, Jonah A; Buch, Karen; Grinstaff, Mark W; Hirsch, Ariel E; Hines, Neely L; Anderson, Stephan W; Gallagher, Katherine M; Bates, David D B; Bloch, B Nicolas

2017-11-01

To evaluate breast biopsy marker migration in stereotactic core needle biopsy procedures and identify contributing factors. This retrospective study analyzed 268 stereotactic biopsy markers placed in 263 consecutive patients undergoing stereotactic biopsies using 9G vacuum-assisted devices from August 2010-July 2013. Mammograms were reviewed and factors contributing to marker migration were evaluated. Basic descriptive statistics were calculated and comparisons were performed based on radiographically-confirmed marker migration. Of the 268 placed stereotactic biopsy markers, 35 (13.1%) migrated ≥1 cm from their biopsy cavity. Range: 1-6 cm; mean (± SD): 2.35 ± 1.22 cm. Of the 35 migrated biopsy markers, 9 (25.7%) migrated ≥3.5 cm. Patient age, biopsy pathology, number of cores, and left versus right breast were not associated with migration status (P> 0.10). Global fatty breast density (P= 0.025) and biopsy in the inner region of breast (P = 0.031) were associated with marker migration. Superior biopsy approach (P= 0.025), locally heterogeneous breast density, and t-shaped biopsy markers (P= 0.035) were significant for no marker migration. Multiple factors were found to influence marker migration. An overall migration rate of 13% supports endeavors of research groups actively developing new biopsy marker designs for improved resistance to migration. • Breast biopsy marker migration is documented in 13% of 268 procedures. • Marker migration is affected by physical, biological, and pathological factors. • Breast density, marker shape, needle approach etc. affect migration. • Study demonstrates marker migration prevalence; marker design improvements are needed.

Biochemical Bone Turnover Markers and Osteoporosis in Older Men: Where Are We?

PubMed Central

Szulc, Pawel

2011-01-01

In men aged less than 60, the association of serum and urinary levels of biochemical bone turnover markers (BTMs) and bone mineral density (BMD) is weak or not significant. After this age, higher BTM levels are correlated weakly, but significantly, with lower BMD and faster bone loss. Limited data from the cohort studies suggest that BTM measurement does not improve the prediction of fragility fractures in older men in comparison with age, BMD, history of falls and fragility fractures. Testosterone replacement therapy (TRT) decreases bone resorption. During TRT, bone formation markers slightly increase (direct effect on osteoblasts), then decrease (slowdown of bone turnover). Bisphosphonates (alendronate, risedronate, ibandronate, zoledronate) induce a rapid decrease in bone resorption followed by a milder decrease in bone formation. In men receiving antiresorptive therapy for prostate cancer, zoledronate, denosumab and toremifene decrease significantly levels of bone resorption and bone formation markers. Teriparatide induced a rapid increase in serum concentrations of bone formation markers followed by an increase in bone resorption. We need more studies on the utility of BTM measurement for the improvement of the persistence and adherence to the anti-osteoporotic treatment in men. PMID:22220284

ANABOLIC BONE WINDOW WITH WEEKLY TERIPARATIDE THERAPY IN POSTMENOPAUSAL OSTEOPOROSIS: A PILOT STUDY.

PubMed

Gopalaswamy, Vinaya; Dhibar, Deba Prasad; Gupta, Vipin; Arya, Ashutosh Kumar; Khandelwal, Niranjan; Bhansali, Anil; Garg, Sudhir Kumar; Agarwal, Neelam; Rao, Sudhaker D; Bhadada, Sanjay Kumar

2017-06-01

Osteoporosis is a major public health problem that reduces bone strength and increases fracture risk. Teriparatide is an established and the only currently available anabolic therapy for the treatment of postmenopausal osteoporosis (PMO) with a recommended daily dose of 20 μg given subcutaneously. However, there are limited data regarding the long-term effect of once-weekly teriparatide therapy on bone mineral density (BMD), bone turnover markers (BTMs), and anabolic bone window. In this prospective observational study, 26 patients with PMO were treated with weekly teriparatide therapy (60 μg) for 2 years. BMD was measured at baseline, 12 months, and 24 months. The bone formation marker type 1 collagen C-terminal propeptide (P1NP) and the bone resorption marker C-terminal telopeptide of type 1 collagen (CTx) were measured at baseline; 6 weeks; and 6, 12, 18, and 24 months. BMDs at the lumbar spine increased by 3.1% and 10.8% after 1 and 2 years of weekly teriparatide therapy, respectively. The T-score increased significantly at the lumbar spine compared to baseline after 2 years of therapy (P = .015). Serum P1NP levels increased significantly at 6 months (P = .024), peaked at 1 year, and remained above the baseline even after 2 years. Serum CTx levels decreased significantly at 6 months (P = .025) and remained below baseline after 2 years of teriparatide therapy. Weekly teriparatide therapy (60 μg) appears to be as effective as daily teriparatide for the treatment of PMO by extending the anabolic bone window. AE = adverse event; BMD = bone mineral density; BTM = bone turnover marker; CTx = C-terminal telopeptide of type 1 collagen; DXA = dual-energy X-ray absorptiometry; iPTH = intact parathyroid hormone; P1NP = type 1 collagen C-terminal propeptide; PMO = postmenopausal osteoporosis.

Pancreatoprotective effects of Geniotrigona thoracica stingless bee honey in streptozotocin-nicotinamide-induced male diabetic rats.

PubMed

Aziz, Muhammad Shakir Abdul; Giribabu, Nelli; Rao, Pasupuleti Visweswara; Salleh, Naguib

2017-05-01

Stingless bee honey (SLBH) has been claimed to possess multiple health benefits. Its anti-diabetic properties are however unknown. In this study, ability of SLBH from Geniotrigona thoracica stingless bee species in ameliorating pancreatic damage and in maintaining metabolic profiles were investigated in diabetic condition. SLBH at 1 and 2g/kg/b.w. was given orally to streptozotocin (STZ)-nicotinamide-induced male diabetic rats for 28days. Metabolic parameters (fasting blood glucose-FBG and lipid profiles-LP and serum insulin) were measured by biochemical assays. Distribution and expression level of insulin, oxidative stress marker i.e. catalase, inflammatory markers i.e. IKK-β, TNF-α, IL-1β and apoptosis marker i.e. caspase-9 in the pancreatic islets were identified and quantified respectively by immunohistochemistry. Levels of NF-κβ in pancreas were determined by enzyme-linked immunoassay (ELISA). SLBH administration to diabetic male rats prevented increase in FBG, total cholesterols (TC), triglyceride (TG) and low density lipoprotein (LDL) levels. However, high density lipoprotein (HDL) and serum insulin levels in diabetic rats receiving SLBH increased. Additionally, histopathological changes and expression level of oxidative stress, inflammation and apoptosis markers in pancreatic islets of diabetic rats decreased with increased expression level of insulin in the islets. LC-MS analysis revealed the presence of several compounds in SLBH that might be responsible for these effects. SLBH has great potential to be used as agent to protect the pancreas against damage and dysfunction where these could account for its anti-diabetic properties. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Genetic background of osteoporosis.

PubMed

Obermayer-Pietsch, B; Chararas, C; Kotschan, S; Walter, D; Leb, G

2000-01-01

Osteoporosis is a systemic disorder of decreased skeletal mass as measured by bone mineral density (BMD), and disturbed skeletal architecture and function which results in an increased risk for bone fractures with consecutively increased morbidity and mortality. Twin and family studies have shown an important genetic component of BMD of about 40-60%. This exceeds other well known factors influencing BMD such as environmental factors like dietary calcium, physical activity or several drugs and diseases. Therefore, interest increased in the genetic background of bone mineral density. Polymorphisms of the Vitamin D receptor gene were the first to be published in this area. Studies on other loci or candidate genes such as the estrogen receptor gene or the collagen type I alpha1 gene also showed associations with bone mineral density that could explain at least a part of the genetic background of osteoporosis. Recently published data suggest that these genetic markers of bone metabolism are important in interaction with each other or in certain bone-affecting diseases. In the future, genetic studies on osteoporosis will have to screen further relevant genes and markers for bone metabolism as well as to evaluate the complex interactions of genetic influences, so that it would be possible to calculate a patient's individual risk for osteoporosis in the context of environmental influences.

Bone mineral density and metabolic indices in hyperthyroidism.

PubMed

Al-Nuaim, A; El-Desouki, M; Sulimani, R; Mohammadiah, M

1991-09-01

Hyperthyroidism can alter bone metabolism by increasing both bone resorption and formation. The increase in bone resorption predominates, leading to a decrease in bone mass. To assess the effect of hyperthyroidism on bone and mineral metabolism, we measured bone density using single photon absorptiometry in 30 untreated hyperthyroid patients. Patients were categorized into three groups based on sex and alkaline phosphatase levels: 44 sex- and age-matched subjects were used as controls. Bone densities were significanlty lower in all patient groups compared with controls. Alkaline phosphatase was found to be a useful marker for assessing severity of bone disease in hyperthyroid patients as there is significant bone density among patients with higher alkaline phosphatase value. Hyperthyroidism should be considered in the differential diagnosis of unexplained alkaline phophatase activity.

Construction of an ultrahigh-density genetic linkage map for Jatropha curcas L. and identification of QTL for fruit yield.

PubMed

Xia, Zhiqiang; Zhang, Shengkui; Wen, Mingfu; Lu, Cheng; Sun, Yufang; Zou, Meiling; Wang, Wenquan

2018-01-01

As an important biofuel plant, the demand for higher yield Jatropha curcas L. is rapidly increasing. However, genetic analysis of Jatropha and molecular breeding for higher yield have been hampered by the limited number of molecular markers available. An ultrahigh-density linkage map for a Jatropha mapping population of 153 individuals was constructed and covered 1380.58 cM of the Jatropha genome, with average marker density of 0.403 cM. The genetic linkage map consisted of 3422 SNP and indel markers, which clustered into 11 linkage groups. With this map, 13 repeatable QTLs (reQTLs) for fruit yield traits were identified. Ten reQTLs, qNF - 1 , qNF - 2a , qNF - 2b , qNF - 2c , qNF - 3 , qNF - 4 , qNF - 6 , qNF - 7a , qNF - 7b and qNF - 8, that control the number of fruits (NF) mapped to LGs 1, 2, 3, 4, 6, 7 and 8, whereas three reQTLs, qTWF - 1 , qTWF - 2 and qTWF - 3, that control the total weight of fruits (TWF) mapped to LGs 1, 2 and 3, respectively. It is interesting that there are two candidate critical genes, which may regulate Jatropha fruit yield. We also identified three pleiotropic reQTL pairs associated with both the NF and TWF traits. This study is the first to report an ultrahigh-density Jatropha genetic linkage map construction, and the markers used in this study showed great potential for QTL mapping. Thirteen fruit-yield reQTLs and two important candidate genes were identified based on this linkage map. This genetic linkage map will be a useful tool for the localization of other economically important QTLs and candidate genes for Jatropha .

Metabolites related to renal function, immune activation, and carbamylation are associated with muscle composition in older adults.

PubMed

Lustgarten, Michael S; Fielding, Roger A

2017-12-15

Reduced skeletal muscle density in older adults is associated with insulin resistance, decreased physical function, and an increased all-cause mortality risk. To elucidate mechanisms that may underlie the maintenance of skeletal muscle density, we conducted a secondary analysis of previously published muscle composition and serum metabolomic data in 73 older adults (average age, 78y). Multivariable-adjusted linear regression was used to examine associations between 321 metabolites with muscle composition, defined as the ratio between normal density (NDM) with low density (LDM) thigh muscle cross sectional area (NDM/LDM). Sixty metabolites were significantly (p≤0.05 and q<0.30) associated with NDM/LDM. Decreased renal function and the immune response have been previously linked with reduced muscle density, but the mechanisms underlying these connections are less clear. Metabolites that were significantly associated with muscle composition were then tested for their association with circulating markers of renal function (blood urea nitrogen, creatinine, uric acid), and with the immune response (neutrophils/lymphocytes) and activation (kynurenine/tryptophan). 43 significant NDM/LDM metabolites (including urea) were co-associated with at least 1 marker of renal function; 23 of these metabolites have been previously identified as uremic solutes. The neutrophil/lymphocyte ratio was significantly associated with NDM/LDM (β±SE: -0.3±0.1, p=0.01, q=0.04). 35 significant NDM/LDM metabolites were co-associated with immune activation. Carbamylation (defined as homocitrulline/lysine) was identified as a pathway that may link renal function and immune activation with muscle composition, as 29 significant NDM/LDM metabolites were co-associated with homocitrulline/lysine, with at least 2 markers of renal function, and with kynurenine/tryptophan. When considering that elevated urea and uremic metabolites have been linked with an increased systemic microbial burden, that antimicrobial defense can be reduced in the presence of carbamylation, and that adipocytes can promote host defense, we propose the novel hypothesis that the age-related increase in adipogenesis within muscle may be a compensatory antimicrobial response to protect against an elevated microbial burden. Copyright © 2017 Elsevier Inc. All rights reserved.

[The effects of oxygen partial pressure changes on the osteometric markers of the bone tissue in rats].

PubMed

Berezovs'kyĭ, V Ia; Zamors'ka, T M; Ianko, R V

2013-01-01

Our purpose was to investigate the oxygen partial pressure changes on the osteometric and biochemical markers of bone tissue in rats. It was shown that breathing of altered gas mixture did not change the mass, general length, sagittal diameter and density thigh-bones in 12-month Wistar male-rats. The dosed normobaric hypoxia increased the activity of alkaline phosphatase and decreased the activity of tartrate-resistant acid phosphatase. At the same time normobaric hyperoxia with 40 and 90% oxygen conversely decreased the activity of alkaline phosphatase and increased the activity of tartrate-resistant acid phosphatase.

High-density linkage mapping revealed suppression of recombination at the sex determination locus in papaya.

PubMed Central

Ma, Hao; Moore, Paul H; Liu, Zhiyong; Kim, Minna S; Yu, Qingyi; Fitch, Maureen M M; Sekioka, Terry; Paterson, Andrew H; Ming, Ray

2004-01-01

A high-density genetic map of papaya (Carica papaya L.) was constructed using 54 F(2) plants derived from cultivars Kapoho and SunUp with 1501 markers, including 1498 amplified fragment length polymorphism (AFLP) markers, the papaya ringspot virus coat protein marker, morphological sex type, and fruit flesh color. These markers were mapped into 12 linkage groups at a LOD score of 5.0 and recombination frequency of 0.25. The 12 major linkage groups covered a total length of 3294.2 cM, with an average distance of 2.2 cM between adjacent markers. This map revealed severe suppression of recombination around the sex determination locus with a total of 225 markers cosegregating with sex types. The cytosine bases were highly methylated in this region on the basis of the distribution of methylation-sensitive and -insensitive markers. This high-density genetic map is essential for cloning of specific genes of interest such as the sex determination gene and for the integration of genetic and physical maps of papaya. PMID:15020433

Osteopenia in anorexia nervosa: specific mechanisms of bone loss.

PubMed

Lennkh, C; de Zwaan, M; Bailer, U; Strnad, A; Nagy, C; el-Giamal, N; Wiesnagrotzki, S; Vytiska, E; Huber, J; Kasper, S

1999-01-01

Osteopenia is a well recognized medical complication of anorexia nervosa (AN). The mechanism of bone loss is not fully understood and there is uncertainty about its management. New markers of bone turnover have been developed. C-terminal type 1 propeptide (PICP) is a measure of bone formation and urinary pyridinolines such as deoxypyridinoline (DPYRX) and serum carboxyterminal crosslinked telopeptide (ICTP) are markers of bone resorption. The aim of this study was to examine these bone markers in patients with AN. Twenty female patients with AN and 12 healthy controls were included in the study. Bone mineral density (BMD) of AN patients was measured by dual energy X-ray absorptiometry (DEXA). Lumbar bone density was significantly reduced in the AN group compared to standardised values of thirty year old adults (t-score 83.2%, S.D. 12.1). Femoral neck bone density showed an even greater reduction (t-score 79.4%, S.D. 13.5). We found a significant negative correlation between femoral BMD and the duration of the illness. Femoral BMD correlated significantly with minimal body weight (r(16) = 0.504, p = 0.033). The markers of bone resorption were significantly higher in the patients with AN compared to the values of the control group (ICTP t(30) = -2.15, p = 0.04, DPYRX t(25) = -2.26, p = 0.033), whereas the markers of bone formation did not differ significantly between the groups. AN appears to be a low turn over state associated with increased bone resorption without concomitant bone formation. This pattern differs from osteopenia in menopausal women and should, therefore, lead to the development of specific therapeutic strategies in AN associated osteopenia. Hormone replacement therapy as well as calcium and vitamine D-supplementation are so far discussed controversially. Long-term treatment studies are warranted.

Longitudinal study of bone loss in chronic spinal cord injury patients

PubMed Central

Karapolat, Inanc; Karapolat, Hale Uzumcugil; Kirazli, Yesim; Capaci, Kazim; Akkoc, Yesim; Kumanlioglu, Kamil

2015-01-01

[Purpose] This prospective longitudinal study evaluated the changes in bone metabolism markers and bone mineral density of spinal cord injury patients over 3 years. We also assessed the relationships among the bone mineral density, bone metabolism, and clinical data of spinal cord injury patients. [Subjects and Methods] We assessed the clinical data (i.e., immobilization due to surgery, neurological status, neurological level, and extent of lesion) in 20 spinal cord injury patients. Bone mineral density, and hormonal and biochemical markers of the patients were measured at 0, 6, 12, and 36 months. [Results] Femoral neck T score decreased significantly at 36 months (p < 0.05). Among the hormonal markers, parathyroid hormone and vitamin D were significantly elevated, while bone turnover markers (i.e., deoxypyridinoline and osteocalcin) were significantly decreased at 12 and 36 months (p < 0.05). [Conclusion] Bone mineral density of the femoral neck decreases significantly during the long-term follow-up of patients with spinal cord injury due to osteoporosis. This could be due to changes in hormonal and bone turnover markers. PMID:26157234

NADPH oxidase 4 limits bone mass by promoting osteoclastogenesis

PubMed Central

Goettsch, Claudia; Babelova, Andrea; Trummer, Olivia; Erben, Reinhold G.; Rauner, Martina; Rammelt, Stefan; Weissmann, Norbert; Weinberger, Valeska; Benkhoff, Sebastian; Kampschulte, Marian; Obermayer-Pietsch, Barbara; Hofbauer, Lorenz C.; Brandes, Ralf P.; Schröder, Katrin

2013-01-01

ROS are implicated in bone diseases. NADPH oxidase 4 (NOX4), a constitutively active enzymatic source of ROS, may contribute to the development of such disorders. Therefore, we studied the role of NOX4 in bone homeostasis. Nox4–/– mice displayed higher bone density and reduced numbers and markers of osteoclasts. Ex vivo, differentiation of monocytes into osteoclasts with RANKL and M-CSF induced Nox4 expression. Loss of NOX4 activity attenuated osteoclastogenesis, which was accompanied by impaired activation of RANKL-induced NFATc1 and c-JUN. In an in vivo model of murine ovariectomy–induced osteoporosis, pharmacological inhibition or acute genetic knockdown of Nox4 mitigated loss of trabecular bone. Human bone obtained from patients with increased osteoclast activity exhibited increased NOX4 expression. Moreover, a SNP of NOX4 was associated with elevated circulating markers of bone turnover and reduced bone density in women. Thus, NOX4 is involved in bone loss and represents a potential therapeutic target for the treatment of osteoporosis. PMID:24216508

Construction and analysis of a high-density genetic linkage map in cabbage (Brassica oleracea L. var. capitata)

PubMed Central

2012-01-01

Background Brassica oleracea encompass a family of vegetables and cabbage that are among the most widely cultivated crops. In 2009, the B. oleracea Genome Sequencing Project was launched using next generation sequencing technology. None of the available maps were detailed enough to anchor the sequence scaffolds for the Genome Sequencing Project. This report describes the development of a large number of SSR and SNP markers from the whole genome shotgun sequence data of B. oleracea, and the construction of a high-density genetic linkage map using a double haploid mapping population. Results The B. oleracea high-density genetic linkage map that was constructed includes 1,227 markers in nine linkage groups spanning a total of 1197.9 cM with an average of 0.98 cM between adjacent loci. There were 602 SSR markers and 625 SNP markers on the map. The chromosome with the highest number of markers (186) was C03, and the chromosome with smallest number of markers (99) was C09. Conclusions This first high-density map allowed the assembled scaffolds to be anchored to pseudochromosomes. The map also provides useful information for positional cloning, molecular breeding, and integration of information of genes and traits in B. oleracea. All the markers on the map will be transferable and could be used for the construction of other genetic maps. PMID:23033896

High-density genetic maps for loci involved in nuclear male sterility (NMS1) and sporophytic self-incompatibility (S-locus) in chicory (Cichorium intybus L., Asteraceae).

PubMed

Gonthier, Lucy; Blassiau, Christelle; Mörchen, Monika; Cadalen, Thierry; Poiret, Matthieu; Hendriks, Theo; Quillet, Marie-Christine

2013-08-01

High-density genetic maps were constructed for loci involved in nuclear male sterility (NMS1-locus) and sporophytic self-incompatibility (S-locus) in chicory (Cichorium intybus L.). The mapping population consisted of 389 F1' individuals derived from a cross between two plants, K28 (male-sterile) and K59 (pollen-fertile), both heterozygous at the S-locus. This F1' mapping population segregated for both male sterility (MS) and strong self-incompatibility (SI) phenotypes. Phenotyping F1' individuals for MS allowed us to map the NMS1-locus to linkage group (LG) 5, while controlled diallel and factorial crosses to identify compatible/incompatible phenotypes mapped the S-locus to LG2. To increase the density of markers around these loci, bulked segregant analysis was used. Bulks and parental plants K28 and K59 were screened using amplified fragment length polymorphism (AFLP) analysis, with a complete set of 256 primer combinations of EcoRI-ANN and MseI-CNN. A total of 31,000 fragments were generated, of which 2,350 showed polymorphism between K59 and K28. Thirteen AFLP markers were identified close to the NMS1-locus and six in the vicinity of the S-locus. From these AFLP markers, eight were transformed into sequence-characterized amplified region (SCAR) markers and of these five showed co-dominant polymorphism. The chromosomal regions containing the NMS1-locus and the S-locus were each confined to a region of 0.8 cM. In addition, we mapped genes encoding proteins similar to S-receptor kinase, the female determinant of sporophytic SI in the Brasicaceae, and also markers in the vicinity of the putative S-locus of sunflower, but none of these genes or markers mapped close to the chicory S-locus.

Age-related changes in bone biochemical markers and their relationship with bone mineral density in normal Chinese women.

PubMed

Pi, Yin-Zhen; Wu, Xian-Ping; Liu, Shi-Ping; Luo, Xiang-Hang; Cao, Xing-Zhi; Xie, Hui; Liao, Er-Yuan

2006-01-01

Measurements of bone biochemical markers are increasingly being used to evaluate the state of bone turnover in the management of bone metabolic diseases, especially osteoporosis. However, changes in the bone turnover rate vary with age. The aim of this study was to establish the laboratory reference range of serum bone-specific alkaline phosphatase (sBAP), serum type I collagen cross-linked C-terminal telopeptide (sCTx), and urine CTx (uCTx), based on values from 665 healthy Chinese women aged 20-80 years. We measured the levels of sBAP, sCTx, serum alkaline phosphatase (sALP), and uCTx and evaluated the age-related changes and their relationship with bone mineral density (BMD) in the anteroposterior (AP) lumbar spine, hip, and left forearm. We found significant correlations between biochemical markers and age, with coefficients of determination (R (2)) of 0.358 for sBAP, 0.126 for sCTx, 0.125 for uCTx, and 0.336 for sALP. The net changes in different biochemical markers were inversely correlated with the rates of BMD loss in the AP lumbar spine. After correction for age, body weight, and height, the levels of the markers had significant negative correlations with the BMD of the AP lumbar spine, femoral neck, and ultradistal forearm. All four biochemical markers had the highest negative correlation with BMD of the AP lumbar spine (partial correlation coefficients of -0.366, -0.296, -0.290, and -0.258 for sBAP, sCTx, uCTx, and sALP, respectively). The mean and SD values of these markers in premenopausal and postmenopausal women with normal BMD values were used as the normal reference ranges. The reference ranges of sBAP, sCTx, and uCTx for pre- vs postmenopausal women were 17.3 +/- 6.23 vs 18.9 +/- 7.52 U/l, 3.18 +/- 1.49 vs 3.23 +/- 1.57 nmol/l, and 15.5 +/- 11.4 vs 16.2 +/- 12.4 nM bone collagen equivalents/mM urinary creatinine, respectively. Levels of the bone formation marker (sBAP) and bone resorption markers (sCTx, uCTx) increased rapidly in women with osteopenia or osteoporosis, indicating that they may be sensitive markers to determine the bone turnover rate in healthy Chinese women.

Effect of tofacitinib on lipid levels and lipid-related parameters in patients with moderate to severe psoriasis.

PubMed

Wolk, Robert; Armstrong, Ehrin J; Hansen, Peter R; Thiers, Bruce; Lan, Shuping; Tallman, Anna M; Kaur, Mandeep; Tatulych, Svitlana

Psoriasis is a systemic inflammatory disease associated with increased cardiovascular (CV) risk and altered lipid metabolism. Tofacitinib is an oral Janus kinase inhibitor. The aim of the study was to investigate the effects of tofacitinib on traditional and nontraditional lipid parameters and CV risk markers in patients with psoriasis from a phase III study, OPT Pivotal 1. Patients with psoriasis were randomized to tofacitinib 5 or 10 mg twice daily (BID) or placebo BID. Serum samples were collected at baseline, week 4, and week 16. Analyses included serum cholesterol levels, triglycerides, lipoproteins, lipid particles, lipid-related parameters/CV risk markers, and high-density lipoprotein (HDL) function analyses. At week 16, small concurrent increases in mean low-density lipoprotein cholesterol (LDL-C) and HDL cholesterol (HDL-C) levels were observed with tofacitinib; total cholesterol/HDL-C ratio did not change. There was no significant change in the number of small dense LDL particles, which are considered to be more atherogenic than large particles, and oxidized LDL did not increase. Paraoxonase 1 activity, linked to HDL antioxidant capacity, increased, and HDL-associated serum amyloid A, which reduces the anti-atherogenic potential of HDL, decreased. HDL capacity to promote cholesterol efflux from macrophages did not change. Lecithin-cholesterol acyltransferase activity, which is associated with reverse cholesterol transport, increased. Markers of systemic inflammation, serum amyloid A and C-reactive protein, decreased with tofacitinib. While small increases in lipid levels are observed with tofacitinib treatment in patients with psoriasis, effects on selected lipid-related parameters and other circulating CV risk biomarkers are not suggestive of an increased CV risk [NCT01276639]. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Quantitative trait loci markers derived from whole genome sequence data increases the reliability of genomic prediction.

PubMed

Brøndum, R F; Su, G; Janss, L; Sahana, G; Guldbrandtsen, B; Boichard, D; Lund, M S

2015-06-01

This study investigated the effect on the reliability of genomic prediction when a small number of significant variants from single marker analysis based on whole genome sequence data were added to the regular 54k single nucleotide polymorphism (SNP) array data. The extra markers were selected with the aim of augmenting the custom low-density Illumina BovineLD SNP chip (San Diego, CA) used in the Nordic countries. The single-marker analysis was done breed-wise on all 16 index traits included in the breeding goals for Nordic Holstein, Danish Jersey, and Nordic Red cattle plus the total merit index itself. Depending on the trait's economic weight, 15, 10, or 5 quantitative trait loci (QTL) were selected per trait per breed and 3 to 5 markers were selected to tag each QTL. After removing duplicate markers (same marker selected for more than one trait or breed) and filtering for high pairwise linkage disequilibrium and assaying performance on the array, a total of 1,623 QTL markers were selected for inclusion on the custom chip. Genomic prediction analyses were performed for Nordic and French Holstein and Nordic Red animals using either a genomic BLUP or a Bayesian variable selection model. When using the genomic BLUP model including the QTL markers in the analysis, reliability was increased by up to 4 percentage points for production traits in Nordic Holstein animals, up to 3 percentage points for Nordic Reds, and up to 5 percentage points for French Holstein. Smaller gains of up to 1 percentage point was observed for mastitis, but only a 0.5 percentage point increase was seen for fertility. When using a Bayesian model accuracies were generally higher with only 54k data compared with the genomic BLUP approach, but increases in reliability were relatively smaller when QTL markers were included. Results from this study indicate that the reliability of genomic prediction can be increased by including markers significant in genome-wide association studies on whole genome sequence data alongside the 54k SNP set. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Medical subject heading (MeSH) annotations illuminate maize genetics and evolution

USDA-ARS?s Scientific Manuscript database

In the modern era, high-density marker panels and/or whole-genome sequencing,coupled with advanced phenotyping pipelines and sophisticated statistical methods, have dramatically increased our ability to generate lists of candidate genes or regions that are putatively associated with phenotypes or pr...

Can non-cholesterol sterols and lipoprotein subclasses distribution predict different patterns of cholesterol metabolism and statin therapy response?

PubMed

Gojkovic, Tamara; Vladimirov, Sandra; Spasojevic-Kalimanovska, Vesna; Zeljkovic, Aleksandra; Vekic, Jelena; Kalimanovska-Ostric, Dimitra; Djuricic, Ivana; Sobajic, Sladjana; Jelic-Ivanovic, Zorana

2017-03-01

Cholesterol homeostasis disorders may cause dyslipidemia, atherosclerosis progression and coronary artery disease (CAD) development. Evaluation of non-cholesterol sterols (NCSs) as synthesis and absorption markers, and lipoprotein particles quality may indicate the dyslipidemia early development. This study investigates associations of different cholesterol homeostasis patterns with low-density (LDL) and high-density lipoproteins (HDL) subclasses distribution in statin-treated and statin-untreated CAD patients, and potential use of aforementioned markers for CAD treatment optimization. The study included 78 CAD patients (47 statin-untreated and 31 statin-treated) and 31 controls (CG). NCSs concentrations were quantified using gas chromatography- flame ionization detection (GC-FID). Lipoprotein subclasses were separated by gradient gel electrophoresis. In patients, cholesterol-synthesis markers were significantly higher comparing to CG. Cholesterol-synthesis markers were inversely associated with LDL size in all groups. For cholesterol homeostasis estimation, each group was divided to good and/or poor synthetizers and/or absorbers according to desmosterol and β-sitosterol median values. In CG, participants with reduced cholesterol absorption, the relative proportion of small, dense LDL was higher in those with increased cholesterol synthesis compared to those with reduced synthesis (p<0.01). LDL I fraction was significantly higher in poor synthetizers/poor absorbers subgroup compared to poor synthetizers/good absorbers (p<0.01), and good synthetizers/poor absorbers (p<0.01). Statin-treated patients with increased cholesterol absorption had increased proportion of LDL IVB (p<0.05). The results suggest the existence of different lipoprotein abnormalities according to various patterns of cholesterol homeostasis. Desmosterol/β-sitosterol ratio could be used for estimating individual propensity toward dyslipidemia development and direct the future treatment.

The construction of a high-density linkage map for identifying SNP markers that are tightly linked to a nuclear-recessive major gene for male sterility in Cryptomeria japonica D. Don

PubMed Central

2012-01-01

Background High-density linkage maps facilitate the mapping of target genes and the construction of partial linkage maps around target loci to develop markers for marker-assisted selection (MAS). MAS is quite challenging in conifers because of their large, complex, and poorly-characterized genomes. Our goal was to construct a high-density linkage map to facilitate the identification of markers that are tightly linked to a major recessive male-sterile gene (ms1) for MAS in C. japonica, a species that is important in Japanese afforestation but which causes serious social pollinosis problems. Results We constructed a high-density saturated genetic linkage map for C. japonica using expressed sequence-derived co-dominant single nucleotide polymorphism (SNP) markers, most of which were genotyped using the GoldenGate genotyping assay. A total of 1261 markers were assigned to 11 linkage groups with an observed map length of 1405.2 cM and a mean distance between two adjacent markers of 1.1 cM; the number of linkage groups matched the basic chromosome number in C. japonica. Using this map, we located ms1 on the 9th linkage group and constructed a partial linkage map around the ms1 locus. This enabled us to identify a marker (hrmSNP970_sf) that is closely linked to the ms1 gene, being separated from it by only 0.5 cM. Conclusions Using the high-density map, we located the ms1 gene on the 9th linkage group and constructed a partial linkage map around the ms1 locus. The map distance between the ms1 gene and the tightly linked marker was only 0.5 cM. The identification of markers that are tightly linked to the ms1 gene will facilitate the early selection of male-sterile trees, which should expedite C. japonica breeding programs aimed at alleviating pollinosis problems without harming productivity. PMID:22424262

Construction of an ultra-high density consensus genetic map, and enhancement of the physical map from genome sequencing in Lupinus angustifolius.

PubMed

Zhou, Gaofeng; Jian, Jianbo; Wang, Penghao; Li, Chengdao; Tao, Ye; Li, Xuan; Renshaw, Daniel; Clements, Jonathan; Sweetingham, Mark; Yang, Huaan

2018-01-01

An ultra-high density genetic map containing 34,574 sequence-defined markers was developed in Lupinus angustifolius. Markers closely linked to nine genes of agronomic traits were identified. A physical map was improved to cover 560.5 Mb genome sequence. Lupin (Lupinus angustifolius L.) is a recently domesticated legume grain crop. In this study, we applied the restriction-site associated DNA sequencing (RADseq) method to genotype an F 9 recombinant inbred line population derived from a wild type × domesticated cultivar (W × D) cross. A high density linkage map was developed based on the W × D population. By integrating sequence-defined DNA markers reported in previous mapping studies, we established an ultra-high density consensus genetic map, which contains 34,574 markers consisting of 3508 loci covering 2399 cM on 20 linkage groups. The largest gap in the entire consensus map was 4.73 cM. The high density W × D map and the consensus map were used to develop an improved physical map, which covered 560.5 Mb of genome sequence data. The ultra-high density consensus linkage map, the improved physical map and the markers linked to genes of breeding interest reported in this study provide a common tool for genome sequence assembly, structural genomics, comparative genomics, functional genomics, QTL mapping, and molecular plant breeding in lupin.

Biochemical markers in the assessment of bone disease

NASA Technical Reports Server (NTRS)

Bikle, D. D.

1997-01-01

As the mean age of our population increases, increasing attention has been paid to the diseases associated with aging, including diseases of the skeleton such as osteoporosis. Effective means of treating and possibly preventing such skeletal disorders are emerging, making their early recognition an important goal for the primary care physician. Although bone density measurements and skeletal imaging studies remain of primary diagnostic importance in this regard, a large number of assays for biochemical markers of bone formation and resorption are being developed that promise to complement the densitometry measurements and imaging studies, providing an assessment of the rates of bone turnover and an earlier evaluation of the effects of therapy. In this review, emphasizing the recent literature, the major biochemical markers currently in use or under active investigation are described, and their application in a number of diseases of the skeleton including osteoporosis is evaluated.

A High-Resolution InDel (Insertion–Deletion) Markers-Anchored Consensus Genetic Map Identifies Major QTLs Governing Pod Number and Seed Yield in Chickpea

PubMed Central

Srivastava, Rishi; Singh, Mohar; Bajaj, Deepak; Parida, Swarup K.

2016-01-01

Development and large-scale genotyping of user-friendly informative genome/gene-derived InDel markers in natural and mapping populations is vital for accelerating genomics-assisted breeding applications of chickpea with minimal resource expenses. The present investigation employed a high-throughput whole genome next-generation resequencing strategy in low and high pod number parental accessions and homozygous individuals constituting the bulks from each of two inter-specific mapping populations [(Pusa 1103 × ILWC 46) and (Pusa 256 × ILWC 46)] to develop non-erroneous InDel markers at a genome-wide scale. Comparing these high-quality genomic sequences, 82,360 InDel markers with reference to kabuli genome and 13,891 InDel markers exhibiting differentiation between low and high pod number parental accessions and bulks of aforementioned mapping populations were developed. These informative markers were structurally and functionally annotated in diverse coding and non-coding sequence components of genome/genes of kabuli chickpea. The functional significance of regulatory and coding (frameshift and large-effect mutations) InDel markers for establishing marker-trait linkages through association/genetic mapping was apparent. The markers detected a greater amplification (97%) and intra-specific polymorphic potential (58–87%) among a diverse panel of cultivated desi, kabuli, and wild accessions even by using a simpler cost-efficient agarose gel-based assay implicating their utility in large-scale genetic analysis especially in domesticated chickpea with narrow genetic base. Two high-density inter-specific genetic linkage maps generated using aforesaid mapping populations were integrated to construct a consensus 1479 InDel markers-anchored high-resolution (inter-marker distance: 0.66 cM) genetic map for efficient molecular mapping of major QTLs governing pod number and seed yield per plant in chickpea. Utilizing these high-density genetic maps as anchors, three major genomic regions harboring each of pod number and seed yield robust QTLs (15–28% phenotypic variation explained) were identified on chromosomes 2, 4, and 6. The integration of genetic and physical maps at these QTLs mapped on chromosomes scaled-down the long major QTL intervals into high-resolution short pod number and seed yield robust QTL physical intervals (0.89–2.94 Mb) which were essentially got validated in multiple genetic backgrounds of two chickpea mapping populations. The genome-wide InDel markers including natural allelic variants and genomic loci/genes delineated at major six especially in one colocalized novel congruent robust pod number and seed yield robust QTLs mapped on a high-density consensus genetic map were found most promising in chickpea. These functionally relevant molecular tags can drive marker-assisted genetic enhancement to develop high-yielding cultivars with increased seed/pod number and yield in chickpea. PMID:27695461

Effects of vitamin D supplementation on 25-hydroxyvitamin D, high-density lipoprotein cholesterol, and other cardiovascular disease risk markers in subjects with elevated waist circumference.

PubMed

Maki, Kevin C; Rubin, Martyn R; Wong, Les G; McManus, Jamie F; Jensen, Christopher D; Lawless, Andrea

2011-06-01

The objective of the present trial was to assess the effects of vitamin D supplementation on serum 25-hydroxyvitamin D [25(OH)D] and high-density lipoprotein cholesterol (HDL-C) in subjects with high waist circumference. Subjects were randomly assigned a daily multivitamin and mineral (MVM) supplement or a MVM supplement plus vitamin D 1,200 IU/day (MVM+D) for 8 weeks. There was a significant difference in mean change for 25(OH)D between the MVM and MVM+D treatment groups ( - 1.2 ± 2.5 nmol/l vs. 11.7 ± 3.0 nmol/l, respectively; P = 0.003). Vitamin D 1,200 IU/day did not increase 25(OH)D to a desirable level ( ≥ 75 nmol/l) in 61% of participants. There were no significant changes in cardiovascular disease risk markers. Thus, vitamin D supplementation with 1,200 IU/day was insufficient to achieve desirable serum 25(OH)D in most participants and did not affect cardiovascular disease risk markers.

A high-density consensus map of barley linking DArT markers to SSR, RFLP and STS loci and agricultural traits

PubMed Central

Wenzl, Peter; Li, Haobing; Carling, Jason; Zhou, Meixue; Raman, Harsh; Paul, Edie; Hearnden, Phillippa; Maier, Christina; Xia, Ling; Caig, Vanessa; Ovesná, Jaroslava; Cakir, Mehmet; Poulsen, David; Wang, Junping; Raman, Rosy; Smith, Kevin P; Muehlbauer, Gary J; Chalmers, Ken J; Kleinhofs, Andris; Huttner, Eric; Kilian, Andrzej

2006-01-01

Background Molecular marker technologies are undergoing a transition from largely serial assays measuring DNA fragment sizes to hybridization-based technologies with high multiplexing levels. Diversity Arrays Technology (DArT) is a hybridization-based technology that is increasingly being adopted by barley researchers. There is a need to integrate the information generated by DArT with previous data produced with gel-based marker technologies. The goal of this study was to build a high-density consensus linkage map from the combined datasets of ten populations, most of which were simultaneously typed with DArT and Simple Sequence Repeat (SSR), Restriction Enzyme Fragment Polymorphism (RFLP) and/or Sequence Tagged Site (STS) markers. Results The consensus map, built using a combination of JoinMap 3.0 software and several purpose-built perl scripts, comprised 2,935 loci (2,085 DArT, 850 other loci) and spanned 1,161 cM. It contained a total of 1,629 'bins' (unique loci), with an average inter-bin distance of 0.7 ± 1.0 cM (median = 0.3 cM). More than 98% of the map could be covered with a single DArT assay. The arrangement of loci was very similar to, and almost as optimal as, the arrangement of loci in component maps built for individual populations. The locus order of a synthetic map derived from merging the component maps without considering the segregation data was only slightly inferior. The distribution of loci along chromosomes indicated centromeric suppression of recombination in all chromosomes except 5H. DArT markers appeared to have a moderate tendency toward hypomethylated, gene-rich regions in distal chromosome areas. On the average, 14 ± 9 DArT loci were identified within 5 cM on either side of SSR, RFLP or STS loci previously identified as linked to agricultural traits. Conclusion Our barley consensus map provides a framework for transferring genetic information between different marker systems and for deploying DArT markers in molecular breeding schemes. The study also highlights the need for improved software for building consensus maps from high-density segregation data of multiple populations. PMID:16904008

[Effect of low-dose or standard-dose conjugated equine estrogen combined with different progesterone on bone density in menopause syndrome women].

PubMed

Zuo, H L; Deng, Y; Wang, Y F; Gao, L L; Xue, W; Zhu, S Y; Ma, X; Sun, A J

2018-04-25

Objective: To explore the effect of low-dose or standard-dose conjugated equine estrogen (CEE) combined with natural progesterone or dydrogesterone on bone density in menopause syndrome women. Methods: Totally 123 patients with menopause syndrome were recruited and randomly assigned to 3 treatment groups: group A (low-dose CEE+progesterone) , group B (standard-dose CEE+progesterone) , group C (standard-dose CEE+dydrogesterone) . Using continuous sequential regimen, the duration of intervention was 12 cycles. The bone mineral density of lumbar 2-4 and neck of femur, the bone metabolic markers, the level of FSH and estradiol were examined just before the drug administration and 12 months after the beginning of experiment. Results: There were 107 cases completed the one year trial. (1) Bone density: after 12 cycles of treatment, there was no significant change in bone density in group A ( P> 0.05) ; lumbar vertebrae of group B and C increased significantly, at 3.0% and 2.1%respectively (all P< 0.05) . The bone density of left femoral neck of group C significantly increased by 2.9% ( P= 0.029) . There was no significant difference among the treatment groups at the beginning of experiment ( P> 0.05) . (2) Bone metabolic markers: after 12 cycles of treatment, the levels of calcium, phosphorus, alkaline phosphatase, Ca/Cr decreased significantly, the difference were statistically significant (all P< 0.05) . There was no significant difference among the treatment groups at the beginning of experiment ( P> 0.05) . (3) Levels of FSH and estradiol: after 12 cycles of treatment, the levels of FSH in three groups were decreased significantly (all P< 0.01) . The levels of estradiol in three groups were increased significantly (all P< 0.01) . There was no significant difference among the treatment groups at the beginning of experiment ( P> 0.05) . Conclusions: Both low-dose and standard-dose menopause hormone therapy (MHT) could elevate the level of estradiol, reduce bone turnover, prevent bone loss of postmenopausal women effectively. The standard dose of MHT could also increase the density of vertebrae and femoral neck, and generate more clinical benefits.

Increasing leaf vein density by mutagenesis: laying the foundations for C4 rice.

PubMed

Feldman, Aryo B; Murchie, Erik H; Leung, Hei; Baraoidan, Marietta; Coe, Robert; Yu, Su-May; Lo, Shuen-Fang; Quick, William P

2014-01-01

A high leaf vein density is both an essential feature of C4 photosynthesis and a foundation trait to C4 evolution, ensuring the optimal proportion and proximity of mesophyll and bundle sheath cells for permitting the rapid exchange of photosynthates. Two rice mutant populations, a deletion mutant library with a cv. IR64 background (12,470 lines) and a T-DNA insertion mutant library with a cv. Tainung 67 background (10,830 lines), were screened for increases in vein density. A high throughput method with handheld microscopes was developed and its accuracy was supported by more rigorous microscopy analysis. Eight lines with significantly increased leaf vein densities were identified to be used as genetic stock for the global C4 Rice Consortium. The candidate population was shown to include both shared and independent mutations and so more than one gene controlled the high vein density phenotype. The high vein density trait was found to be linked to a narrow leaf width trait but the linkage was incomplete. The more genetically robust narrow leaf width trait was proposed to be used as a reliable phenotypic marker for finding high vein density variants in rice in future screens.

High-throughput single nucleotide polymorphism genotyping for breeding applications in rice using the BeadXpress platform

USDA-ARS?s Scientific Manuscript database

Multiplexed single nucleotide polymorphism (SNP) markers have the potential to increase the speed and cost-effectiveness of genotyping, provided that an optimal SNP density is used for each application. To test the efficiency of multiplexed SNP genotyping for diversity, mapping and breeding applicat...

High-throughput SNP genotyping for breeding applications in rice using the BeadXpress platform

USDA-ARS?s Scientific Manuscript database

Multiplexed single nucleotide polymorphism (SNP) markers have the potential to increase the speed and cost-effectiveness of genotyping, provided that an optimal SNP density is used for each application. To test the efficiency of multiplexed SNP genotyping for diversity, mapping and breeding applicat...

Salmonid Chromosome Evolution as Revealed by a Novel Method for Comparing RADseq Linkage Maps

PubMed Central

Gosselin, Thierry; Normandeau, Eric; Lamothe, Manuel; Isabel, Nathalie; Audet, Céline; Bernatchez, Louis

2016-01-01

Whole genome duplication (WGD) can provide material for evolutionary innovation. Family Salmonidae is ideal for studying the effects of WGD as the ancestral salmonid underwent WGD relatively recently, ∼65 Ma, then rediploidized and diversified. Extensive synteny between homologous chromosome arms occurs in extant salmonids, but each species has both conserved and unique chromosome arm fusions and fissions. Assembly of large, outbred eukaryotic genomes can be difficult, but structural rearrangements within such taxa can be investigated using linkage maps. RAD sequencing provides unprecedented ability to generate high-density linkage maps for nonmodel species, but can result in low numbers of homologous markers between species due to phylogenetic distance or differences in library preparation. Here, we generate a high-density linkage map (3,826 markers) for the Salvelinus genera (Brook Charr S. fontinalis), and then identify corresponding chromosome arms among the other available salmonid high-density linkage maps, including six species of Oncorhynchus, and one species for each of Salmo, Coregonus, and the nonduplicated sister group for the salmonids, Northern Pike Esox lucius for identifying post-duplicated homeologs. To facilitate this process, we developed MapComp to identify identical and proximate (i.e. nearby) markers between linkage maps using a reference genome of a related species as an intermediate, increasing the number of comparable markers between linkage maps by 5-fold. This enabled a characterization of the most likely history of retained chromosomal rearrangements post-WGD, and several conserved chromosomal inversions. Analyses of RADseq-based linkage maps from other taxa will also benefit from MapComp, available at: https://github.com/enormandeau/mapcomp/ PMID:28173098

CD163 as a marker of M2 macrophage, contribute to predicte aggressiveness and prognosis of Kazakh esophageal squamous cell carcinoma.

PubMed

Hu, Jian Ming; Liu, Kai; Liu, Ji Hong; Jiang, Xian Li; Wang, Xue Li; Chen, Yun Zhao; Li, Shu Gang; Zou, Hong; Pang, Li Juan; Liu, Chun Xia; Cui, Xiao Bin; Yang, Lan; Zhao, Jin; Shen, Xi Hua; Jiang, Jin Fang; Liang, Wei Hua; Yuan, Xiang Lin; Li, Feng

2017-03-28

M2 macrophages was domesticated by tumor microenvironment to produce some angiogenic molecules and protease, facilitating angiogenesis and matrix breakdown, promoting tumor invasive and metastasis. However, The function of M2 macrophages to progression of eophageal carcinoma, especially Kazakh esophageal carcinoma is still dimness. This study aims to investigate M2 macrophages correlated with matrix metalloproteinase-9 (MMP9) and microvessel density, and the role in the progression of Kazakh esophageal squamous cell carcinoma. CD163 and CD34 as the marker of M2 macrophages and endothelial cells, were used to identify the M2 macrophages density and microvessel density, respectively. Immunohistochemistry staining was evaluated the expression of MMP9. The number of infiltrated CD163-positive M2 macrophages in tumor islets and stroma was significantly higher than in cancer adjacent normal tissues. The increased of M2 macrophages and microvessel density were significantly correlated with more malignant phenotypes including lymph node metastasis and clinical stage progression. Meanwhile, the expression of MMP9 showed much higher level in esophageal squamous cell carcinoma than that in cancer adjacent normal tissues, and high expression of MMP9 in Kazakh esophageal squamous cell carcinoma was significantly associated with age, depth of tumor invasion, lymph node metastasis, and tumor clinical stage. The quantity of M2 macrophages in tumor stroma was positively associated with microvessel density and the expression of MMP9, and as an independent poorly prognostic factor for overall survival time of Kazakh esophageal squamous cell carcinoma. These findings suggest the increased number of M2 macrophages correlated with high expression of MMP9 and high microvessel density may contribute to the tumor aggressiveness and angiogenesis, promoting the progression of Kazakh esophageal squamous cell carcinoma.

Effects of tamoxifen on bone mineral density and metabolism in postmenopausal women with early-stage breast cancer.

PubMed

Zidan, Jamal; Keidar, Zohar; Basher, Walid; Israel, Ora

2004-01-01

At the present time, tamoxifen is the most widely used anti-estrogen for adjuvant therapy and metastatic disease in postmenopausal women with breast cancer, a population at high risk for osteoporosis. This prospective study was designed to evaluate the effect of adjuvant tamoxifen on bone mineral density and all biochemical markers concomitantly in women with early-stage breast cancer in one study. Using dual-energy X-ray absorptiometry, prior to and 12 mo after tamoxifen treatment, bone mineral density in lumbar spine and femoral neck was measured in 44 women with T1-T2N0M0 estrogen-receptor-positive breast cancer receiving adjuvant treatment with tamoxifen 20 mg/d. Biomarkers that can affect bone mineral metabolism were measured before and after 3 and 12 mo of tamoxifen treatment. Bone mineral density was minimally increased in lumbar spine and femoral neck after 12 mo treatment with tamoxifen (p = 0.79 and 0.55, respectively). No differences were found in serum levels of calcium, phosphate, creatinine, ALAT, albumin, LDH, calcitonin, or estradiol. A significant decrease in osteocalcin levels was found after 3 and 12 mo (p < or = 0.01). TSH and PTH levels were increased (p < or = 0.05) after 3 mo, returning to baseline after 12 mo. In conclusion, tamoxifen has an estrogen-like effect on bone metabolism in postmenopausal women and is associated with preservation of bone mineral density in lumbar spine and femoral neck. Changes in serum concentration of biochemical markers may reflect decreased bone turnover or bone remodeling and add to the understanding of tamoxifen's effect on bone mineral density.

Obesity and Associated Cardiometabolic Risk among Women from Tripura - A Northeastern State of India.

PubMed

Sen, Purnajita; Das, Sandeep; Hore, Samrat; Bhattacharjee, Surajit; Choudhuri, Dipayan

2017-01-01

Cardiometabolic health status of women is a serious public health concern. Markers of body fat content and their distribution are important indicators of cardiometabolic health risk in participants. In addition, socio-demographic status plays a determinant role. The aim of the study was to evaluate the influence of adiposity markers and socio-demographic determinants on various cardiovascular and metabolic risk factors in Indian women. The study was conducted on 388 women (age 25-65 years) from Tripura, a Northeastern state of India. Various obesity and atherogenic markers such as body mass index (BMI), waist circumference (WC), waist-hip ratio, waist - height ratio, high density lipoprotein-cholesterol (HDL-C)/total cholesterol, HDL-C/low density lipoprotein cholesterol, triglyceride/HDL-C ratio and traditional cardiometabolic risk factors such as high blood pressure, dyslipidemia, and glucose intolerance were evaluated in participant. The socio-demographic status included the level of education and monthly family income. The cardiometabolic risk in postmenopausal women were higher than premenopausal women. The risk increases with age in both groups. Women with lower educational level and higher income group were found to be prone to higher cardiometabolic risk. Receiver operating characteristics analysis revealed central obesity marked by increased WC was a better predictor of cardiometabolic risk than general obesity marked by increased BMI. The cardiometabolic risk among both premenopausal and postmenopausal women are associated with central obesity which can be predicted by increased WC in the subject. Socio-demographic status of the participant plays a definitive role in determining cardiometabolic risk in women.

The effect of exemestane and tamoxifen on bone health within the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial: a meta-analysis of the US, German, Netherlands, and Belgium sub-studies.

PubMed

Hadji, Peyman; Asmar, Lina; van Nes, Johanna G H; Menschik, Thomas; Hasenburg, Annette; Kuck, Joachim; Nortier, Johan W R; van de Velde, Cornelis J H; Jones, Stephen E; Ziller, May

2011-06-01

We performed a meta-analysis of three sub-studies of the randomized Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial to determine the effects of exemestane and tamoxifen on bone health. Patients received exemestane or tamoxifen as adjuvant therapy for hormone receptor-positive breast cancer. Bone mineral density (BMD) was assessed at baseline and after 12 and 24 months of treatment. Bone turnover markers were also measured. Patients receiving tamoxifen showed a mean increase from baseline in lumbar spine BMD of 1.2% at month 12 and 0.2% at month 24. Patients receiving exemestane showed a mean decrease from baseline of 2.6% after 12 months and 3.5% after 24 months. There were significant differences in the changes in lumbar spine BMD between treatment groups (P < 0.0001 at both time points). Changes in BMD from baseline at the total hip were also significantly different between exemestane and tamoxifen (P < 0.05 at both time points). Bone turnover markers decreased from baseline with tamoxifen and increased with exemestane. Exemestane resulted in decreases in BMD and increases in bone turnover markers. BMD increased and bone turnover markers decreased with tamoxifen.

Temporal and spatial distribution of macrophage phenotype markers in the foreign body response to glutaraldehyde-crosslinked gelatin hydrogels.

PubMed

Yu, Tony; Wang, Wenbo; Nassiri, Sina; Kwan, Thomas; Dang, Chau; Liu, Wei; Spiller, Kara L

2016-01-01

Currently, it is not well understood how changes in biomaterial properties affect the foreign body response (FBR) or macrophage behavior. Because failed attempts at biomaterial degradation by macrophages have been linked to frustrated phagocytosis, a defining feature of the FBR, we hypothesized that increased hydrogel crosslinking density (and decreased degradability) would exacerbate the FBR. Gelatin hydrogels were crosslinked with glutaraldehyde (0.05, 0.1, and 0.3%) and implanted subcutaneously in C57BL/6 mice over the course of 3 weeks. Interestingly, changes in hydrogel crosslinking did not affect the thickness of the fibrous capsule surrounding the hydrogels, expression of the pan-macrophage marker F480, expression of three macrophage phenotype markers (iNOS, Arg1, CD163), or expression of the myofibroblast marker aSMA, determined using semi-quantitative immunohistochemical analysis. With respect to temporal changes, the level of expression of the M1 marker (iNOS) remained relatively constant throughout the study, while the M2 markers Arg1 and CD163 increased over time. Expression of these M2 markers was highly correlated with fibrous capsule thickness. Differences in spatial distribution of staining also were noted, with the strongest staining for iNOS at the hydrogel surface and increasing expression of the myofibroblast marker aSMA toward the outer edge of the fibrous capsule. These results confirm previous reports that macrophages in the FBR exhibit characteristics of both M1 and M2 phenotypes. Understanding the effects (or lack of effects) of biomaterial properties on the FBR and macrophage phenotype may aid in the rational design of biomaterials to integrate with surrounding tissue.

Interruption or deferral of antiretroviral therapy reduces markers of bone turnover compared with continuous therapy: the SMART Body Composition Substudy

PubMed Central

Hoy, Jennifer; Grund, Birgit; Roediger, Mollie; Ensrud, Kristine E.; Brar, Indira; Colebunders, Robert; De Castro, Nathalie; Johnson, Margaret; Sharma, Anjali; Carr, Andrew

2013-01-01

Bone mineral density (BMD) declines significantly in HIV patients on antiretroviral therapy (ART). We compared the effects of intermittent versus continuous ART on markers of bone turnover in the Body Composition substudy of the Strategies for Management of AntiRetroviral Therapy (SMART) trial and determined whether early changes in markers predicted subsequent change in BMD. For 202 participants (median age 44 years, 17% female, 74% on ART) randomised to continuous or intermittent ART, plasma markers of inflammation and bone turnover were evaluated at baseline, months 4 and 12; BMD at the spine (dual X-ray absorptiometry [DXA] and computed tomography) and hip (DXA) was evaluated annually. Compared to the continuous ART group, mean bone-specific alkaline phosphatase (bALP), osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), N-terminal cross-linking telopeptide of type 1 collagen (NTX), and C-terminal cross-linking telopeptide of type 1 collagen (βCTX) decreased significantly in the intermittent ART group, whereas RANKL and the RANKL:osteoprotegerin (OPG) ratio increased (all p≤0.002 at month 4 and month 12). Increases in bALP, osteocalcin, P1NP, NTX, and βCTX at month 4 predicted decrease in hip BMD at month 12, while increases in RANKL and the RANKL:OPG ratio at month 4 predicted increase in hip and spine BMD at month 12. This study has shown that compared with continuous ART, interruption of ART results in a reduction in markers of bone turnover and increase in BMD at hip and spine, and that early changes in markers of bone turnover predict BMD changes at 12 months. PMID:23299909

A reference consensus genetic map for molecular markers and economically important traits in faba bean (Vicia faba L.)

PubMed Central

2013-01-01

Background Faba bean (Vicia faba L.) is among the earliest domesticated crops from the Near East. Today this legume is a key protein feed and food worldwide and continues to serve an important role in culinary traditions throughout Middle East, Mediterranean region, China and Ethiopia. Adapted to a wide range of soil types, the main faba bean breeding objectives are to improve yield, resistance to biotic and abiotic stresses, seed quality and other agronomic traits. Genomic approaches aimed at enhancing faba bean breeding programs require high-quality genetic linkage maps to facilitate quantitative trait locus analysis and gene tagging for use in a marker-assisted selection. The objective of this study was to construct a reference consensus map in faba bean by joining the information from the most relevant maps reported so far in this crop. Results A combination of two approaches, increasing the number of anchor loci in diverse mapping populations and joining the corresponding genetic maps, was used to develop a reference consensus map in faba bean. The map was constructed from three main recombinant inbreed populations derived from four parental lines, incorporates 729 markers and is based on 69 common loci. It spans 4,602 cM with a range from 323 to 1041 loci in six main linkage groups or chromosomes, and an average marker density of one locus every 6 cM. Locus order is generally well maintained between the consensus map and the individual maps. Conclusion We have constructed a reliable and fairly dense consensus genetic linkage map that will serve as a basis for genomic approaches in faba bean research and breeding. The core map contains a larger number of markers than any previous individual map, covers existing gaps and achieves a wider coverage of the large faba bean genome as a whole. This tool can be used as a reference resource for studies in different genetic backgrounds, and provides a framework for transferring genetic information when using different marker technologies. Combined with syntenic approaches, the consensus map will increase marker density in selected genomic regions and will be useful for future faba bean molecular breeding applications. PMID:24377374

Disrupted Bone Metabolism in Long-Term Bedridden Patients

PubMed Central

Endo, Naoto; Uchiyama, Seiji; Takahashi, Yoshinori; Kawashima, Hiroyuki; Watanabe, Kei

2016-01-01

Background Bedridden patients are at risk of osteoporosis and fractures, although the long-term bone metabolic processes in these patients are poorly understood. Therefore, we aimed to determine how long-term bed confinement affects bone metabolism. Methods This study included 36 patients who had been bedridden from birth due to severe immobility. Bone mineral density and bone metabolism markers were compared to the bedridden period in all study patients. Changes in the bone metabolism markers during a follow-up of 12 years were studied in 17 patients aged <30 years at baseline. Results The bone mineral density was reduced (0.58±0.19 g/cm3), and the osteocalcin (13.9±12.4 ng/mL) and urine N-terminal telopeptide (NTX) levels (146.9±134.0 mM BCE/mM creatinine) were greater than the cutoff value for predicting fracture. Among the bone metabolism markers studied, osteocalcin and NTX were negatively associated with the bedridden period. During the follow-up, osteocalcin and parathyroid hormone were decreased, and the 25(OH) vitamin D was increased. NTX at baseline was negatively associated with bone mineral density after 12 years. Conclusions Unique bone metabolic abnormalities were found in patients who had been bedridden for long periods, and these metabolic abnormalities were altered by further bed confinement. Appropriate treatment based on the unique bone metabolic changes may be important in long-term bedridden patients. PMID:27275738

Disrupted Bone Metabolism in Long-Term Bedridden Patients.

PubMed

Eimori, Keiko; Endo, Naoto; Uchiyama, Seiji; Takahashi, Yoshinori; Kawashima, Hiroyuki; Watanabe, Kei

2016-01-01

Bedridden patients are at risk of osteoporosis and fractures, although the long-term bone metabolic processes in these patients are poorly understood. Therefore, we aimed to determine how long-term bed confinement affects bone metabolism. This study included 36 patients who had been bedridden from birth due to severe immobility. Bone mineral density and bone metabolism markers were compared to the bedridden period in all study patients. Changes in the bone metabolism markers during a follow-up of 12 years were studied in 17 patients aged <30 years at baseline. The bone mineral density was reduced (0.58±0.19 g/cm3), and the osteocalcin (13.9±12.4 ng/mL) and urine N-terminal telopeptide (NTX) levels (146.9±134.0 mM BCE/mM creatinine) were greater than the cutoff value for predicting fracture. Among the bone metabolism markers studied, osteocalcin and NTX were negatively associated with the bedridden period. During the follow-up, osteocalcin and parathyroid hormone were decreased, and the 25(OH) vitamin D was increased. NTX at baseline was negatively associated with bone mineral density after 12 years. Unique bone metabolic abnormalities were found in patients who had been bedridden for long periods, and these metabolic abnormalities were altered by further bed confinement. Appropriate treatment based on the unique bone metabolic changes may be important in long-term bedridden patients.

A study of changes in bone metabolism in cases of gender identity disorder.

PubMed

Miyajima, Tsuyoshi; Kim, Yoon Taek; Oda, Hiromi

2012-07-01

The aim of this study was to determine the effect of increasing estrogen and decreasing androgen in males and increasing androgen and decreasing estrogen in females on bone metabolism in patients with gender identity disorder (GID). We measured and examined bone mineral density (BMD) and bone metabolism markers retrospectively in GID patients who were treated in our hospital. In addition, we studied the effects of treatment on those who had osteoporosis. Patients who underwent a change from male to female (MtF) showed inhibition of bone resorption and increased L2-4 BMD whereas those who underwent a change from female to male (FtM) had increased bone resorption and decreased L2-4 BMD. Six months after administration of risedronate to FtM patients with osteoporosis, L2-4 BMD increased and bone resorption markers decreased. These results indicate that estrogen is an important element with regard to bone metabolism in males.

Modulatory efficacy of green tea polyphenols on glycoconjugates and immunological markers in 4-Nitroquinoline 1-oxide-induced oral carcinogenesis-A therapeutic approach.

PubMed

Srinivasan, Periasamy; Sabitha, Kuruvimalai Ekambaram; Shyamaladevi, Chennam Srinivasulu

2006-08-25

Green tea polyphenols (GTP) has been used as a chemopreventive agent world wide against chemically induced cancer. The present study is aimed to understand the therapeutic action of GTP on glycoconjugates and immunological markers in 4-Nitroquinoline 1-oxide (4-NQO)-induced oral cancer over a period of 30 days at 200mg/kg, p.o., Oral cancer was induced by painting 4-NQO for 8 weeks followed by administration of GTP after 22 weeks, for 30 days. Glycoconjugates such as hexose, hexosamine, sialicacid, fucose and mucoprotein were analysed. Expression of glycoconjugates was examined through histology and SDS-PAGE. Immunological markers such as circulating immune complex and mast cell density were studied. Oral cancer-induced animals showed a significant increase in levels of glycoconjugates and its expression, similar to that observed for immunological markers. Treatment with GTP altered the expression of glycoconjugates as well as immunological markers. The results suggest that GTP modulates both the expression of glycoconjugates and immunological markers resulting in regression of oral cancer.

FGF21 decreases body weight without reducing food intake or bone mineral density in high-fat fed obese rhesus macaque monkeys.

PubMed

Andersen, Birgitte; Straarup, Ellen M; Heppner, Kristy M; Takahashi, Diana L; Raffaele, Virginia; Dissen, Gregory A; Lewandowski, Katherine; Bödvarsdottir, Thóra B; Raun, Kirsten; Grove, Kevin L; Kievit, Paul

2018-06-11

Administration of FGF21 and FGF21 analogues reduce body weight; improve insulin sensitivity and dyslipidemia in animal models of obesity and in short term clinical trials. However potential adverse effects identified in mice have raised concerns for the development of FGF21 therapeutics. Therefore, this study was designed to address the actions of FGF21 on body weight, glucose and lipid metabolism and importantly its effects on bone mineral density (BMD), bone markers, and plasma cortisol in high-fat fed obese rhesus macaque monkeys. Obese non-diabetic rhesus macaque monkeys (five males and five ovariectomized (OVX) females) were maintained on a high-fat diet and treated for 12 weeks with escalating doses of FGF21. Food intake was assessed daily and body weight weekly. Bone mineral content (BMC) and BMD were measured by DEXA scanning prior to the study and on several occasions throughout the treatment period as well as during washout. Plasma glucose, glucose tolerance, insulin, lipids, cortisol, and bone markers were likewise measured throughout the study. On average, FGF21 decreased body weight by 17.6 ± 1.6% after 12 weeks of treatment. No significant effect on food intake was observed. No change in BMC or BMD was observed, while a 2-fold increase in CTX-1, a marker of bone resorption, was seen. Overall glucose tolerance was improved with a small but significant decrease in HbA 1C . Furthermore, FGF21 reduced concentrations of plasma triglycerides and very low density lipoprotein cholesterol. No adverse changes in clinical chemistry markers were demonstrated, and no alterations in plasma cortisol were observed during the study. In conclusion, FGF21 reduced body weight in obese rhesus macaque monkeys without reducing food intake. Furthermore, FGF21 had beneficial effects on body composition, insulin sensitivity, and plasma triglycerides. No adverse effects on bone density or plasma cortisol were observed after 12 weeks of treatment.

Genomic imputation and evaluation using high density Holstein genotypes

USDA-ARS?s Scientific Manuscript database

Genomic evaluations for 161,341 Holsteins were computed using 311,725 of the 777,962 markers on the Illumina high-density (HD) chip. Initial edits with 1,741 HD genotypes from 5 breeds revealed that 636,967 markers were usable but that half were redundant. Usable Holstein genotypes included 1,510 an...

Toward allotetraploid cotton genome assembly: integration of a high-density molecular genetic linkage map with DNA sequence information

PubMed Central

2012-01-01

Background Cotton is the world’s most important natural textile fiber and a significant oilseed crop. Decoding cotton genomes will provide the ultimate reference and resource for research and utilization of the species. Integration of high-density genetic maps with genomic sequence information will largely accelerate the process of whole-genome assembly in cotton. Results In this paper, we update a high-density interspecific genetic linkage map of allotetraploid cultivated cotton. An additional 1,167 marker loci have been added to our previously published map of 2,247 loci. Three new marker types, InDel (insertion-deletion) and SNP (single nucleotide polymorphism) developed from gene information, and REMAP (retrotransposon-microsatellite amplified polymorphism), were used to increase map density. The updated map consists of 3,414 loci in 26 linkage groups covering 3,667.62 cM with an average inter-locus distance of 1.08 cM. Furthermore, genome-wide sequence analysis was finished using 3,324 informative sequence-based markers and publicly-available Gossypium DNA sequence information. A total of 413,113 EST and 195 BAC sequences were physically anchored and clustered by 3,324 sequence-based markers. Of these, 14,243 ESTs and 188 BACs from different species of Gossypium were clustered and specifically anchored to the high-density genetic map. A total of 2,748 candidate unigenes from 2,111 ESTs clusters and 63 BACs were mined for functional annotation and classification. The 337 ESTs/genes related to fiber quality traits were integrated with 132 previously reported cotton fiber quality quantitative trait loci, which demonstrated the important roles in fiber quality of these genes. Higher-level sequence conservation between different cotton species and between the A- and D-subgenomes in tetraploid cotton was found, indicating a common evolutionary origin for orthologous and paralogous loci in Gossypium. Conclusion This study will serve as a valuable genomic resource for tetraploid cotton genome assembly, for cloning genes related to superior agronomic traits, and for further comparative genomic analyses in Gossypium. PMID:23046547

Single nucleotide polymorphism markers for genetic mapping in Drosophila melanogaster

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoskins, Roger A.; Phan, Alexander C.; Naeemuddin, Mohammed

2001-04-16

For nearly a century, genetic analysis in Drosophila melanogaster has been a powerful tool for analyzing gene function, yet Drosophila lacks the molecular genetic mapping tools that have recently revolutionized human, mouse and plant genetics. Here, we describe the systematic characterization of a dense set of molecular markers in Drosophila using an STS-based physical map of the genome. We identify 474 biallelic markers in standard laboratory strains of Drosophila that the genome. The majority of these markers are single nucleotide polymorphisms (SNPs) and sequences for these variants are provided in an accessible format. The average density of the new markersmore » is 1 marker per 225 kb on the autosomes and 1 marker per 1 Mb on the X chromosome. We include in this survey a set of P-element strains that provide additional utility for high-resolution mapping. We demonstrate one application of the new markers in a simple set of crosses to map a mutation in the hedgehog gene to an interval of <1 Mb. This new map resource significantly increases the efficiency and resolution of recombination mapping and will be of immediate value to the Drosophila research community.« less

Pathogenic bacteria and microbial-source tracking markers in Brandywine Creek Basin, Pennsylvania and Delaware, 2009-10

USGS Publications Warehouse

Duris, Joseph W.; Reif, Andrew G.; Olson, Leif E.; Johnson, Heather E.

2011-01-01

The City of Wilmington, Delaware, is in the downstream part of the Brandywine Creek Basin, on the main stem of Brandywine Creek. Wilmington uses this stream, which drains a mixed-land-use area upstream, for its main drinking-water supply. Because the stream is used for drinking water, Wilmington is in need of information about the occurrence and distribution of specific fecally derived pathogenic bacteria (disease-causing bacteria) and their relations to commonly measured fecal-indicator bacteria (FIB), as well as information regarding the potential sources of the fecal pollution and pathogens in the basin. This study focused on five routinely sampled sites within the basin, one each on the West Branch and the East Branch of Brandywine Creek and at three on the main stem below the confluence of the West and East Branches. These sites were sampled monthly for 1 year. Targeted event samples were collected on two occasions during high flow and two occasions during normal flow. On the basis of this study, high flows in the Brandywine Creek Basin were related to increases in FIB densities, and in the frequency of selected pathogen and source markers, in the West Branch and main stem of Brandywine Creek, but not in the East Branch. Water exceeding the moderate fullbody-contact single-sample recreational water-quality criteria (RWQC) for Escherichia coli (E. coli) was more likely to contain selected markers for pathogenic E. coli (eaeA,stx1, and rfbO157 gene markers) and bovine fecal sources (E. hirae and LTIIa gene markers), whereas samples exceeding the enterococci RWQC were more likely to contain the same pathogenic markers but also were more likely to carry a marker indicative of human source (esp gene marker). On four sample dates, during high flow between October and March, the West Branch was the only observed potential contributor of selected pathogen and bovine source markers to the main stem of Brandywine Creek. Indeed, the stx2 marker, which indicates a highly virulent type of pathogenic E. coli, was found only in the West Branch and main stem at high flow but was not found in the East Branch under similar conditions. However, it must be noted that throughout the entire year of sampling there were occasions, during both high and normal flows, when both the East and West Branches were potential contributors of pathogen and microbial-source tracking markers to the main stem. Therefore, this study indicates that under selected conditions (high flow, October through March), West Branch Brandywine Creek Basin was the most likely source of elevated FIB densities in the main stem. These elevated densities are associated with more frequent detection of selected pathogenic E. coli markers (rfbO157 stx1) and are associated with MST markers of bovine source. However, during other times of the year, both the West Branch and East Branch Basins are acting as potential sources of FIB and fecally derived pathogens.

The extent of linkage disequilibrium in beef cattle breeds using high-density SNP genotypes.

PubMed

Porto-Neto, Laercio R; Kijas, James W; Reverter, Antonio

2014-03-24

The extent of linkage disequilibrium (LD) between molecular markers impacts genome-wide association studies and implementation of genomic selection. The availability of high-density single nucleotide polymorphism (SNP) genotyping platforms makes it possible to investigate LD at an unprecedented resolution. In this work, we characterised LD decay in breeds of beef cattle of taurine, indicine and composite origins and explored its variation across autosomes and the X chromosome. In each breed, LD decayed rapidly and r2 was less than 0.2 for marker pairs separated by 50 kb. The LD decay curves clustered into three groups of similar LD decay that distinguished the three main cattle types. At short distances between markers (<10 kb), taurine breeds showed higher LD (r2=0.45) than their indicine (r2=0.25) and composite (r2=0.32) counterparts. This higher LD in taurine breeds was attributed to a smaller effective population size and a stronger bottleneck during breed formation. Using all SNPs on only the X chromosome, the three cattle types could still be distinguished. However for taurine breeds, the LD decay on the X chromosome was much faster and the background level much lower than for indicine breeds and composite populations. When using only SNPs that were polymorphic in all breeds, the analysis of the X chromosome mimicked that of the autosomes. The pattern of LD mirrored some aspects of the history of breed populations and showed a sharp decay with increasing physical distance between markers. We conclude that the availability of the HD chip can be used to detect association signals that remained hidden when using lower density genotyping platforms, since LD dropped below 0.2 at distances of 50 kb.

Survey and analysis of simple sequence repeats in the Laccaria bicolor genome, with development of microsatellite markers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Labbe, Jessy L; Murat, Claude; Morin, Emmanuelle

It is becoming clear that simple sequence repeats (SSRs) play a significant role in fungal genome organization, and they are a large source of genetic markers for population genetics and meiotic maps. We identified SSRs in the Laccaria bicolor genome by in silico survey and analyzed their distribution in the different genomic regions. We also compared the abundance and distribution of SSRs in L. bicolor with those of the following fungal genomes: Phanerochaete chrysosporium, Coprinopsis cinerea, Ustilago maydis, Cryptococcus neoformans, Aspergillus nidulans, Magnaporthe grisea, Neurospora crassa and Saccharomyces cerevisiae. Using the MISA computer program, we detected 277,062 SSRs in themore » L. bicolor genome representing 8% of the assembled genomic sequence. Among the analyzed basidiomycetes, L. bicolor exhibited the highest SSR density although no correlation between relative abundance and the genome sizes was observed. In most genomes the short motifs (mono- to trinucleotides) were more abundant than the longer repeated SSRs. Generally, in each organism, the occurrence, relative abundance, and relative density of SSRs decreased as the repeat unit increased. Furthermore, each organism had its own common and longest SSRs. In the L. bicolor genome, most of the SSRs were located in intergenic regions (73.3%) and the highest SSR density was observed in transposable elements (TEs; 6,706 SSRs/Mb). However, 81% of the protein-coding genes contained SSRs in their exons, suggesting that SSR polymorphism may alter gene phenotypes. Within a L. bicolor offspring, sequence polymorphism of 78 SSRs was mainly detected in non-TE intergenic regions. Unlike previously developed microsatellite markers, these new ones are spread throughout the genome; these markers could have immediate applications in population genetics.« less

Pulse Wave Amplitude Drops during Sleep are Reliable Surrogate Markers of Changes in Cortical Activity

PubMed Central

Delessert, Alexandre; Espa, Fabrice; Rossetti, Andrea; Lavigne, Gilles; Tafti, Mehdi; Heinzer, Raphael

2010-01-01

Background: During sleep, sudden drops in pulse wave amplitude (PWA) measured by pulse oximetry are commonly associated with simultaneous arousals and are thought to result from autonomic vasoconstriction. In the present study, we determine whether PWA drops were associated with changes in cortical activity as determined by EEG spectral analysis. Methods: A 20% decrease in PWA was chosen as a minimum for a drop. A total of 1085 PWA drops from 10 consecutive sleep recordings were analyzed. EEG spectral analysis was performed over 5 consecutive epochs of 5 seconds: 2 before, 1 during, and 2 after the PWA drop. EEG spectral analysis was performed over delta, theta, alpha, sigma, and beta frequency bands. Within each frequency band, power density was compared across the five 5-sec epochs. Presence or absence of visually scored EEG arousals were adjudicated by an investigator blinded to the PWA signal and considered associated with PWA drop if concomitant. Results: A significant increase in EEG power density in all EEG frequency bands was found during PWA drops (P < 0.001) compared to before and after drop. Even in the absence of visually scored arousals, PWA drops were associated with a significant increase in EEG power density (P < 0.001) in most frequency bands. Conclusions: Drops in PWA are associated with a significant increase in EEG power density, suggesting that these events can be used as a surrogate for changes in cortical activity during sleep. This approach may prove of value in scoring respiratory events on limited-channel (type III) portable monitors. Citation: Delessert A; Espa F; Rossetti A; Lavigne G; Tafti M; Heinzer R. Pulse wave amplitude drops during sleep are reliable surrogate markers of changes in cortical activity. SLEEP 2010;33(12):1687-1692. PMID:21120131

Construction of a high-density genetic map and the X/Y sex-determining gene mapping in spinach based on large-scale markers developed by specific-locus amplified fragment sequencing (SLAF-seq).

PubMed

Qian, Wei; Fan, Guiyan; Liu, Dandan; Zhang, Helong; Wang, Xiaowu; Wu, Jian; Xu, Zhaosheng

2017-04-04

Cultivated spinach (Spinacia oleracea L.) is one of the most widely cultivated types of leafy vegetable in the world, and it has a high nutritional value. Spinach is also an ideal plant for investigating the mechanism of sex determination because it is a dioecious species with separate male and female plants. Some reports on the sex labeling and localization of spinach in the study of molecular markers have surfaced. However, there have only been two reports completed on the genetic map of spinach. The lack of rich and reliable molecular markers and the shortage of high-density linkage maps are important constraints in spinach research work. In this study, a high-density genetic map of spinach based on the Specific-locus Amplified Fragment Sequencing (SLAF-seq) technique was constructed; the sex-determining gene was also finely mapped. Through bio-information analysis, 50.75 Gb of data in total was obtained, including 207.58 million paired-end reads. Finally, 145,456 high-quality SLAF markers were obtained, with 27,800 polymorphic markers and 4080 SLAF markers were finally mapped onto the genetic map after linkage analysis. The map spanned 1,125.97 cM with an average distance of 0.31 cM between the adjacent marker loci. It was divided into 6 linkage groups corresponding to the number of spinach chromosomes. Besides, the combination of Bulked Segregation Analysis (BSA) with SLAF-seq technology(super-BSA) was employed to generate the linkage markers with the sex-determining gene. Combined with the high-density genetic map of spinach, the sex-determining gene X/Y was located at the position of the linkage group (LG) 4 (66.98 cM-69.72 cM and 75.48 cM-92.96 cM), which may be the ideal region for the sex-determining gene. A high-density genetic map of spinach based on the SLAF-seq technique was constructed with a backcross (BC 1 ) population (which is the highest density genetic map of spinach reported at present). At the same time, the sex-determining gene X/Y was mapped to LG4 with super-BSA. This map will offer a suitable basis for further study of spinach, such as gene mapping, map-based cloning of Specific genes, quantitative trait locus (QTL) mapping and marker-assisted selection (MAS). It will also provide an efficient reference for studies on the mechanism of sex determination in other dioecious plants.

Genomic predictions can accelerate selection for resistance against Piscirickettsia salmonis in Atlantic salmon (Salmo salar).

PubMed

Bangera, Rama; Correa, Katharina; Lhorente, Jean P; Figueroa, René; Yáñez, José M

2017-01-31

Salmon Rickettsial Syndrome (SRS) caused by Piscirickettsia salmonis is a major disease affecting the Chilean salmon industry. Genomic selection (GS) is a method wherein genome-wide markers and phenotype information of full-sibs are used to predict genomic EBV (GEBV) of selection candidates and is expected to have increased accuracy and response to selection over traditional pedigree based Best Linear Unbiased Prediction (PBLUP). Widely used GS methods such as genomic BLUP (GBLUP), SNPBLUP, Bayes C and Bayesian Lasso may perform differently with respect to accuracy of GEBV prediction. Our aim was to compare the accuracy, in terms of reliability of genome-enabled prediction, from different GS methods with PBLUP for resistance to SRS in an Atlantic salmon breeding program. Number of days to death (DAYS), binary survival status (STATUS) phenotypes, and 50 K SNP array genotypes were obtained from 2601 smolts challenged with P. salmonis. The reliability of different GS methods at different SNP densities with and without pedigree were compared to PBLUP using a five-fold cross validation scheme. Heritability estimated from GS methods was significantly higher than PBLUP. Pearson's correlation between predicted GEBV from PBLUP and GS models ranged from 0.79 to 0.91 and 0.79-0.95 for DAYS and STATUS, respectively. The relative increase in reliability from different GS methods for DAYS and STATUS with 50 K SNP ranged from 8 to 25% and 27-30%, respectively. All GS methods outperformed PBLUP at all marker densities. DAYS and STATUS showed superior reliability over PBLUP even at the lowest marker density of 3 K and 500 SNP, respectively. 20 K SNP showed close to maximal reliability for both traits with little improvement using higher densities. These results indicate that genomic predictions can accelerate genetic progress for SRS resistance in Atlantic salmon and implementation of this approach will contribute to the control of SRS in Chile. We recommend GBLUP for routine GS evaluation because this method is computationally faster and the results are very similar with other GS methods. The use of lower density SNP or the combination of low density SNP and an imputation strategy may help to reduce genotyping costs without compromising gain in reliability.

Effects of surface finishing conditions on the biocompatibility of a nickel-chromium dental casting alloy.

PubMed

McGinley, Emma Louise; Coleman, David C; Moran, Gary P; Fleming, Garry J P

2011-07-01

To assess the effects of surface finishing condition (polished or alumina particle air abraded) on the biocompatibility of direct and indirect exposure to a nickel-chromium (Ni-Cr) d.Sign®10 dental casting alloy on oral keratinocytes. Biocompatibility was performed by assessing cellular viability and morphology, metabolic activity, cellular toxicity and presence of inflammatory cytokine markers. Discs of d.Sign®10 were cast, alumina particle air abraded and half were polished before surface roughness was determined by profilometry. Biocompatibility was assessed by placing the discs directly or indirectly (with immersion solutions) into contact with TR146 monolayers. Metal ion release was determined by ICP-MS. Cell viability was assessed by trypan blue dye exclusion, metabolic activity by XTT and cellular toxicity by LDH. Inflammatory cytokine analysis was performed using sandwich ELISAs. The mean polished Ra value was significantly reduced (P<0.001) compared with the alumina particle air abraded discs but metal ion release was significantly increased for the polished discs. Significant reductions in cell density of polished compared with alumina particle air abraded discs was observed following direct or indirect exposure. A significant reduction in metabolic activity, increase in cellular toxicity and an increase in the presence of inflammatory cytokine markers was highlighted for the polished relative to the alumina particle air abraded discs at 24h. Finishing condition of the Ni-Cr dental alloy investigated has important clinical implications. The approach of employing cell density and morphology, metabolic activity, cellular toxicity levels and inflammatory marker responses to TR146 epithelial cells combined with ICP-MS afforded the authors an increased insight into the complex processes dental alloys undergo in the oral environment. Copyright © 2011 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Lipid Profiles, Inflammatory Markers, and Insulin Therapy in Youth with Type 2 Diabetes.

PubMed

Levitt Katz, Lorraine E; Bacha, Fida; Gidding, Samuel S; Weinstock, Ruth S; El Ghormli, Laure; Libman, Ingrid; Nadeau, Kristen J; Porter, Kristin; Marcovina, Santica

2018-05-01

Data regarding atherogenic dyslipidemia and the inflammation profile in youth with type 2 diabetes is limited and the effect of insulin therapy on these variables has not previously been studied in youth. We determined the impact of insulin therapy on lipid and inflammatory markers in youth with poorly controlled type 2 diabetes. In the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) multicenter trial, 285 participants failed to sustain glycemic control on randomized treatment (primary outcome, glycated hemoglobin A1c [HbA1c] at ≥8% for 6 months); 363 maintained glycemic control (never reached primary outcome). Statins were used for a low-density lipoprotein cholesterol of ≥130 mg/dL. Upon reaching the primary outcome, insulin was started. Changes in lipids and inflammatory markers (slopes over time) were examined. Progression of dyslipidemia was related to glycemic control. In those with the primary outcome, insulin therapy impacted HbA1c modestly, and dampened the increase in total cholesterol, low-density lipoprotein cholesterol, and total apolipoprotein B, although statin use increased from 8.6% to 22% year after the primary outcome. The increase in triglycerides and plasma nonesterified fatty acids stabilized after insulin was started, independent of HbA1c. There was an increase in high-sensitivity C-reactive protein that continued after insulin initiation, related to HbA1c and percent overweight. Worsening dyslipidemia and inflammation over time raise concern regarding premature development of atherosclerosis in youth with type 2 diabetes. Insulin therapy has a limited benefit in the absence of glycemic control. Strategies to achieve better glycemic control are needed. ClinicalTrials.gov: NCT00081328. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of angiotensin II receptor blocker, olmesartan, on turnover of bone metabolism in bedridden elderly hypertensive women with disuse syndrome.

PubMed

Aoki, Motokuni; Kawahata, Hirohisa; Sotobayashi, Daisuke; Yu, Hisahiro; Moriguchi, Atsushi; Nakagami, Hironori; Ogihara, Toshio; Morishita, Ryuichi

2015-08-01

Although recent studies suggest that several antihypertensive drugs could reduce the risk of bone fracture, it is still unclear how these drugs act on bone remodeling, especially in elderly women with severe osteoporosis with disuse syndrome. In the present study, we investigated the effects of a calcium channel blocker (CCB) and an angiotensin II receptor blocker (ARB) on bone metabolism in elderly bedridden women with hypertension and disuse syndrome. Elderly bedridden women (aged >75 years) receiving antihypertensive therapy treated with CCB were recruited in the present study. The participants were divided into two groups--CCB group and ARB group--and followed up to 12 months. Markers of bone resorption were markedly increased, suggesting accelerated bone resorption in the participants of the present study. In the follow-up period, the patients treated with a CCB showed a significant decrease in bone mineral density in a time-dependent manner, accompanied by a significant increase in bone resorption markers, whereas treatment with olmesartan inhibited bone loss, associated with attenuation of increased bone resorption markers. Bone mineral density of femoral neck in the CCB group was significantly lower than that in the ARB group at 6 months. The present study showed inhibitory effects of an ARB on bone resorption in hypertensive patients with accelerated bone resorption, such as elderly bedridden women, and indicated an important role of the renin-angiotensin system in bone metabolism. In elderly hypertensive patients, ARB might be expected to have additional beneficial potential to maintain bone health in bedridden patients. © 2014 Japan Geriatrics Society.

Geographical segregation and IL-6: a marker of chronic inflammation in older adults.

PubMed

Purser, Jama L; Kuchibhatla, Maragatha N; Miranda, Marie L; Blazer, Dan G; Cohen, Harvey J; Fillenbaum, Gerda G

2008-01-01

AIM: To examine environmental sociodemographic risks of high IL-6, a marker of chronic inflammation in older adults. METHODS: We spatially linked 1990 USA Census tract demographic and economic measures to a prospective cohort study of representative community residents aged 71 years and older, from over 1700 of whom a cytokine protein and biological marker of chronic inflammation. IL-6, was collected. Using generalized interactive mixed models, we modeled 1989-1990 individual and census level risk factors for the dependent variable high IL-6 between 1992-1993 (high IL-6 = upper quartile: >2.96 pg/ml). RESULTS: After individual health risk adjustment, IL-6 remained elevated in communities with greater densities of poor older adults (odd ratio [OR]: 1.25 per 10% increase in exposure. 95% confidence interval [CI]: 1.05, 1.48) and in racially segregated communities (OR: 1.14 per 10% increase in exposure. 95% CI: 1.04, 1.25). CONCLUSIONS: Socially disadvantaged environments may influence IL-6, a biomarker of age-associated inflammation.

Expression of Lipid Peroxidation Markers in the Tear Film and Ocular Surface of Patients with Non-Sjogren Syndrome: Potential Biomarkers for Dry Eye Disease.

PubMed

Choi, Won; Lian, Cui; Ying, Li; Kim, Ga Eon; You, In Cheon; Park, Soo Hyun; Yoon, Kyung Chul

2016-09-01

To investigate the expression of lipid peroxidation markers in the tear film and ocular surface and their correlation with disease severity in patients with dry eye disease. The concentrations of hexanoyl-lysine (HEL), 4-hydroxy-2-nonenal (HNE), and malondialdehyde (MDA) were measured with enzyme-linked immunosorbent assays in tears obtained from 44 patients with non-Sjogren syndrome dry eye and 33 control subjects. The correlations between the marker levels and the tear film and ocular surface parameters, including tear film break-up time (BUT), Schirmer tear value, tear clearance rate, keratoepitheliopathy scores, corneal sensitivity, conjunctival goblet cell density, and symptom score, were analyzed. The expression of the lipid peroxidation markers HEL, 4-HNE, and MDA in the conjunctiva was evaluated using immunohistochemistry. The concentrations of HEL, 4-HNE, and MDA were 279.84 ± 69.98 nmol/L, 0.02 ± 0.01 μg/mL, and 3.80 ± 1.05 pmol/mg in control subjects and 283.21 ± 89.67 nmol/L (p = 0.97), 0.20 ± 0.03 μg/mL (p < 0.01), and 13.32 ± 4.03 pmol/mg (p < 0.01) in dry eye patients. 4-HNE and MDA levels significantly correlated with BUT, Schirmer tear value, tear clearance rate, keratoepitheliopathy scores, conjunctival goblet cell density, and symptom score (p < 0.05), whereas HEL levels did not correlate with these parameters. Staining intensities for 4-HNE and MDA increased in dry eye patients. The expression of late lipid peroxidation markers, 4-HNE and MDA, increases in the tear film and ocular surface of patients with dry eye. The levels correlate with various tear film and ocular surface parameters and may reflect the severity of dry eye disease.

Accuracy of Genomic Prediction for Foliar Terpene Traits in Eucalyptus polybractea.

PubMed

Kainer, David; Stone, Eric A; Padovan, Amanda; Foley, William J; Külheim, Carsten

2018-06-11

Unlike agricultural crops, most forest species have not had millennia of improvement through phenotypic selection, but can contribute energy and material resources and possibly help alleviate climate change. Yield gains similar to those achieved in agricultural crops over millennia could be made in forestry species with the use of genomic methods in a much shorter time frame. Here we compare various methods of genomic prediction for eight traits related to foliar terpene yield in Eucalyptus polybractea , a tree grown predominantly for the production of Eucalyptus oil. The genomic markers used in this study are derived from shallow whole genome sequencing of a population of 480 trees. We compare the traditional pedigree-based additive best linear unbiased predictors (ABLUP), genomic BLUP (GBLUP), BayesB genomic prediction model, and a form of GBLUP based on weighting markers according to their influence on traits (BLUP|GA). Predictive ability is assessed under varying marker densities of 10,000, 100,000 and 500,000 SNPs. Our results show that BayesB and BLUP|GA perform best across the eight traits. Predictive ability was higher for individual terpene traits, such as foliar α-pinene and 1,8-cineole concentration (0.59 and 0.73, respectively), than aggregate traits such as total foliar oil concentration (0.38). This is likely a function of the trait architecture and markers used. BLUP|GA was the best model for the two biomass related traits, height and 1 year change in height (0.25 and 0.19, respectively). Predictive ability increased with marker density for most traits, but with diminishing returns. The results of this study are a solid foundation for yield improvement of essential oil producing eucalypts. New markets such as biopolymers and terpene-derived biofuels could benefit from rapid yield increases in undomesticated oil-producing species. Copyright © 2018, G3: Genes, Genomes, Genetics.

Strontium ranelate effect on bone mineral density is modified by previous bisphosphonate treatment.

PubMed

Brun, Lucas R; Galich, Ana M; Vega, Eduardo; Salerni, Helena; Maffei, Laura; Premrou, Valeria; Costanzo, Pablo R; Sarli, Marcelo A; Rey, Paula; Larroudé, María S; Moggia, María S; Brance, María L; Sánchez, Ariel

2014-01-01

The aim of this study was to evaluate the effect of strontium ranelate (SrR) on bone mineral density (BMD) and bone turnover markers after 1 year of treatment. Additionally, the effect of SrR in bisphosphonate-naïve patients (BP-naïve) compared to patients previously treated with bisphosphonates (BP-prior) was analyzed. This retrospective study included 482 postmenopausal women treated with SrR (2 g/day) for 1 year in ten Argentine centers; 41 patients were excluded due to insufficient data, while 441 were included. Participants were divided according to previous bisphosphonate treatment in two groups: BP-naïve (n = 87) and BP-prior (n = 350). Data are expressed as mean ± SEM. After 1 year of treatment with SrR the bone formation markers total alkaline phosphatase and osteocalcin were increased (p < 0.0001), while the bone resorption marker s-CTX was decreased (p = 0.0579). Also increases in BMD at the lumbar spine (LS, 3.73%), femoral neck (FN, 2.00%) and total hip (TH, 1.54%) [p < 0.0001] were observed. These increments were significant (p < 0.0001) both among BP-naïve and BP-prior patients. Interestingly, the change in BMD after 1 year of SrR treatment was higher in BP-naïve patients: LS: BP-naïve = 4.58 ± 0.62%; BP-prior = 3.45 ± 0.28% (p = 0.078). FN: BP-naïve = 2.79 ± 0.56%; BP-prior = 2.13 ± 0.29% (p = 0.161). TH: BP-naïve = 3.01 ± 0.55%; BP-prior = 1.22 ± 0.27% (p = 0.0006). SrR treatment increased BMD and bone formation markers and decreased a bone resorption marker in the whole group, with better response in BP-naïve patients.

Development of an experimental diet model in rats to study hyperlipidemia and insulin resistance, markers for coronary heart disease.

PubMed

Munshi, Renuka P; Joshi, Samidha G; Rane, Bhagyeshri N

2014-01-01

The objective of this study is to develop an experimental model of hyperlipidemia and insulin resistance (IR), markers of coronary heart disease (CHD) using high fat and high sugar (HFHS) diet and to evaluate the efficacy of the model using atorvastatin, a known antihyperlipidemic drug, pioglitazone, a known insulin sensitizer, and Tinospora cordifolia (Tc), an antidiabetic plant. Following Institutional Animal Ethics Committee permission, the study was conducted in male Wistar rats (200-270 g). The model was developed using a high fat (vanaspati ghee: coconut oil, 3:1) oral diet along with 25% fructose (high sugar) added in drinking water over a period of 6 weeks. Atorvastatin (2.1 mg/kg/day), pioglitazone (2.7 mg/kg/day) and Tc (200 mg/kg/day) were administered 3 weeks after initiation of HFHS diet and continued for another 3 weeks. Parameters assessed were weight, lipid profile, fasting blood glucose, insulin, and gastric emptying. Serum malondialdehyde (MDA) and catalase were assessed as markers of oxidative stress. Administration of HFHS diet demonstrated a significant increase in blood glucose, insulin, total and low density lipoprotein cholesterol and triglycerides with a decrease in high density lipoprotein cholesterol. Treatment with test drugs decreased blood sugar, insulin, lipid parameters, increased gastric emptying rate, decreased MDA levels, and catalase activity when compared to HFHS diet group, confirming the efficacy of the model. Atherogenic index of all the test drugs (0.48, 0.57, and 0.53) was significantly lower as compared to HFHS diet group (1.107). This study confirms the development of a diet based cost-effective and time efficient experimental model, which can be used to study two important markers of cardiovascular disease that is, hyperlipidemia and IR and to explore the efficacy of new molecules in CHD.

Adiposity in Children and CVD Risk: ApoB48 Has a Stronger Association With Central Fat Than Classic Lipid Markers.

PubMed

Wilke, Michaelann S; Maximova, Katerina; Henderson, Mélanie; Levy, Emile; Paradis, Gilles; O'Loughlin, Jennifer; Tremblay, Angelo; Proctor, Spencer D

2016-07-01

Atherosclerotic vascular disease begins in childhood and while progression is multifactorial, obesity in early life is an important risk factor for its development. To determine whether fasting apoB48 remnant lipoproteins (relative to classic lipid markers), is elevated with increasing central adiposity over time in a cohort of Canadian children with a family history of obesity. Data were drawn from the ongoing prospective cohort of 630 Caucasian families in Québec, Canada, recruited to assess determinants and effects of childhood obesity (Québec Adiposity and Lifestyle Investigation in Youth [QUALITY]cohort). Children who attended baseline and first followup clinic visits (n =570; age 9.6 y). Trunk fat mass was determined by dual energy x-ray absorptiometry. Central fat mass index was calculated as CFMI = trunk fat mass/height(2) (kg/m(2)) and groups created (CFMI <1.5; 1.5-3.0; ≥3.0 kg/m(2)) to suggest lower, moderate, or higher central adiposity. Changes over time in outcomes (apoB48, triglyceride and total, low-, and high-density lipoprotein cholesterol) were compared using paired t test and multiple regression that adjusted for age, sex, and Tanner stage. Classic lipid markers (total and low-density lipoprotein cholesterol) improved at followup, whereas apoB48 became worse (increased). ApoB48 increased with increasing central adiposity, highest (37%) in children who transitioned from lower- to moderate-CFMI groups (ΔapoB48 = 1.5 μg/mL). For every 1 kg/m(2) increase in central adiposity over the 2-y period, an increase in apoB48 was 14-fold greater among children with lower baseline CFMI, compared with higher CFMI. Increased fasting concentrations of apoB48 may be representative of changes in adiposity at lower levels of central fat (early periods of risk).

Opposing effects on glutathione and reactive oxygen metabolites of sex, habitat, and spring date, but no effect of increased breeding density in great tits (Parus major)

PubMed Central

Isaksson, Caroline

2013-01-01

Abstract Oxidative stress (i.e., more oxidants than antioxidants) has been proposed as a proximate currency in life-history trade-offs, which if studied in an ecological setting allow a more realistic perspective on the origin and evolution of trade-offs. Therefore, the aim here was to investigate the impact of ecological and individual factors for variation in markers of oxidative stress using both experimental and correlational data. Total glutathione (tGSH), oxidized glutathione (GSSG), plasma antioxidant capacity (OXY), and plasma-reactive oxygen metabolites (ROM) were measured in more than 700 breeding great tits (Parus major). The main results revealed a pronounced sex difference, with females having lower ROM and OXY, but higher tGSH compared with males. In addition, birds breeding in the evergreen areas had higher tGSH compared with those in the deciduous habitat, but the experimentally manipulated breeding density had no significant effect on any of the redox markers. Independent of the sex differences, the larger the reproductive investment the lower the ROM of both males and females. Taken together, the extracellular markers – ROM and OXY – revealed similar results and were highly correlated. Interestingly, the direction of their effects was in the opposite direction to the endogenously synthesized tGSH and GSSG. This highlights the need to combine extracellular markers with endogenously synthesized antioxidants to understand its implications for the origin and evolution of trade-offs in an ecological setting. Oxidative stress has been proposed as a proximate currency in life-history trade-offs, which if studied in an ecological setting allow a more realistic perspective on the origin and evolution of trade-offs. Here multiple markers of oxidative stress were analysed in wild great tits. The results reveal that the endogenously synthesized antioxidant glutathione and markers of plasma oxidative stress are affected in opposing directions with regard to sex, habitat type, and spring date. Clutch size was negatively associated with oxidative damage, which suggests that those with high reproductive investment can combat physiological costs linked to oxidative stress. The experimentally manipulated breeding density did not influence oxidative stress physiology. The study highlights the need to measure multiple markers to understand the role of oxidative stress in limiting the expression of life-history traits and trajectories in different ecological contexts. PMID:24567835

Exploring a new bilateral focal density asymmetry based image marker to predict breast cancer risk

NASA Astrophysics Data System (ADS)

Aghaei, Faranak; Mirniaharikandehei, Seyedehnafiseh; Hollingsworth, Alan B.; Wang, Yunzhi; Qiu, Yuchen; Liu, Hong; Zheng, Bin

2017-03-01

Although breast density has been widely considered an important breast cancer risk factor, it is not very effective to predict risk of developing breast cancer in a short-term or harboring cancer in mammograms. Based on our recent studies to build short-term breast cancer risk stratification models based on bilateral mammographic density asymmetry, we in this study explored a new quantitative image marker based on bilateral focal density asymmetry to predict the risk of harboring cancers in mammograms. For this purpose, we assembled a testing dataset involving 100 positive and 100 negative cases. In each of positive case, no any solid masses are visible on mammograms. We developed a computer-aided detection (CAD) scheme to automatically detect focal dense regions depicting on two bilateral mammograms of left and right breasts. CAD selects one focal dense region with the maximum size on each image and computes its asymmetrical ratio. We used this focal density asymmetry as a new imaging marker to divide testing cases into two groups of higher and lower focal density asymmetry. The first group included 70 cases in which 62.9% are positive, while the second group included 130 cases in which 43.1% are positive. The odds ratio is 2.24. As a result, this preliminary study supported the feasibility of applying a new focal density asymmetry based imaging marker to predict the risk of having mammography-occult cancers. The goal is to assist radiologists more effectively and accurately detect early subtle cancers using mammography and/or other adjunctive imaging modalities in the future.

The relationship between breast density and bone mineral density in postmenopausal women.

PubMed

Buist, Diana S M; Anderson, Melissa L; Taplin, Stephen H; LaCroix, Andrea Z

2004-11-01

It is not well understood whether breast density is a marker of cumulative exposure to estrogen or a marker of recent exposure to estrogen. The authors examined the relationship between bone mineral density (BMD; a marker of lifetime estrogen exposure) and breast density. The authors conducted a cross-sectional analysis among 1800 postmenopausal women > or = 54 years. BMD data were taken from two population-based studies conducted in 1992-1993 (n = 1055) and in 1998-1999 (n = 753). The authors linked BMD data with breast density information collected as part of a mammography screening program. They used linear regression to evaluate the density relationship, adjusted for age, hormone therapy use, body mass index (BMI), and reproductive covariates. There was a small but significant negative association between BMD and breast density. The negative correlation between density measures was not explained by hormone therapy or age, and BMI was the only covariate that notably influenced the relationship. Stratification by BMI only revealed the negative correlation between bone and breast densities in women with normal BMI. There was no relationship in overweight or obese women. The same relationship was seen for all women who had never used hormone therapy, but it was not significant once stratified by BMI. BMD and breast density were not positively associated although both are independently associated with estrogen exposure. It is likely that unique organ responses obscure the relationship between the two as indicators of cumulative estrogen exposure.

QTL meta-analysis of root traits in Brassica napus under contrasting phosphorus supply in two growth systems

PubMed Central

Zhang, Ying; Thomas, Catherine L.; Xiang, Jinxia; Long, Yan; Wang, Xiaohua; Zou, Jun; Luo, Ziliang; Ding, Guangda; Cai, Hongmei; Graham, Neil S.; Hammond, John P.; King, Graham J.; White, Philip J.; Xu, Fangsen; Broadley, Martin R.; Shi, Lei; Meng, Jinling

2016-01-01

A high-density SNP-based genetic linkage map was constructed and integrated with a previous map in the Tapidor x Ningyou7 (TNDH) Brassica napus population, giving a new map with a total of 2041 molecular markers and an average marker density which increased from 0.39 to 0.97 (0.82 SNP bin) per cM. Root and shoot traits were screened under low and ‘normal’ phosphate (Pi) supply using a ‘pouch and wick’ system, and had been screened previously in an agar based system. The P-efficient parent Ningyou7 had a shorter primary root length (PRL), greater lateral root density (LRD) and a greater shoot biomass than the P-inefficient parent Tapidor under both treatments and growth systems. Quantitative trait loci (QTL) analysis identified a total of 131 QTL, and QTL meta-analysis found four integrated QTL across the growth systems. Integration reduced the confidence interval by ~41%. QTL for root and shoot biomass were co-located on chromosome A3 and for lateral root emergence were co-located on chromosomes A4/C4 and C8/C9. There was a major QTL for LRD on chromosome C9 explaining ~18% of the phenotypic variation. QTL underlying an increased LRD may be a useful breeding target for P uptake efficiency in Brassica. PMID:27624881

Momordica charantia polysaccharides ameliorate oxidative stress, hyperlipidemia, inflammation, and apoptosis during myocardial infarction by inhibiting the NF-κB signaling pathway.

PubMed

Raish, Mohammad

2017-04-01

The polysaccharide extract of Momordica charantia has various biological activities; however, its effect on endothelial dysfunction in myocardial infarction remains unclear. To elucidate this, myocardial infarction was induced in rats using isoproterenol (ISP). Pretreatment with M. charantia polysaccharides (MCP; 150 or 300mg/kg) for 25days significantly inhibited increases in heart weight, the heart-weight-to-body-weight ratio, and infarction size, and ameliorated the increased serum levels of aspartate transaminase, creatine kinase, lactate dehydrogenase, total cholesterol, triglycerides, very-low-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. In addition, MCP enhanced the activity of superoxide dismutase, catalase, and non-protein sulfhydryls, and decreased the level of lipid peroxidation. Moreover, MCP pretreatment downregulated the expression of proinflammatory cytokines (tumor necrosis factor alpha, interleukin (IL)-6, and IL-10), inflammatory markers (nitric oxide, myeloperoxidase, and inducible nitric oxide synthase), and apoptotic markers (caspase-3 and BAX), and upregulated Bcl-2 expression. Pretreatment with MCP reduced myonecrosis, edema, and inflammatory cell infiltration, and restored cardiomyocytes architecture. This myocardial protective effect could be related to the enhancement of the antioxidant defense system through the nuclear factor kappa B (NF-kB) pathways, and to anti-apoptosis through regulation of Bax, caspase-3, and Bcl-2. Copyright © 2017 Elsevier B.V. All rights reserved.

Genome survey and high-density genetic map construction provide genomic and genetic resources for the Pacific White Shrimp Litopenaeus vannamei

PubMed Central

Yu, Yang; Zhang, Xiaojun; Yuan, Jianbo; Li, Fuhua; Chen, Xiaohan; Zhao, Yongzhen; Huang, Long; Zheng, Hongkun; Xiang, Jianhai

2015-01-01

The Pacific white shrimp Litopenaeus vannamei is the dominant crustacean species in global seafood mariculture. Understanding the genome and genetic architecture is useful for deciphering complex traits and accelerating the breeding program in shrimp. In this study, a genome survey was conducted and a high-density linkage map was constructed using a next-generation sequencing approach. The genome survey was used to identify preliminary genome characteristics and to generate a rough reference for linkage map construction. De novo SNP discovery resulted in 25,140 polymorphic markers. A total of 6,359 high-quality markers were selected for linkage map construction based on marker coverage among individuals and read depths. For the linkage map, a total of 6,146 markers spanning 4,271.43 cM were mapped to 44 sex-averaged linkage groups, with an average marker distance of 0.7 cM. An integration analysis linked 5,885 genome scaffolds and 1,504 BAC clones to the linkage map. Based on the high-density linkage map, several QTLs for body weight and body length were detected. This high-density genetic linkage map reveals basic genomic architecture and will be useful for comparative genomics research, genome assembly and genetic improvement of L. vannamei and other penaeid shrimp species. PMID:26503227

Age-Related Shifts in the Density and Distribution of Genetic Marker Water Quality Indicators in Cow and Calf Feces (Journal)

EPA Science Inventory

Calves (≤ 226 kg body mass) make up about 16% of the current bovine population in the United States and can excrete high levels of human pathogens. We describe the density and distribution of genetic markers from 11 PCR- and real-time quantitative PCR-based assays including CF...

A high density genetic map and QTL for agronomic and yield traits in Foxtail millet [Setaria italica (L.) P. Beauv].

PubMed

Fang, Xiaomei; Dong, Kongjun; Wang, Xiaoqin; Liu, Tianpeng; He, Jihong; Ren, Ruiyu; Zhang, Lei; Liu, Rui; Liu, Xueying; Li, Man; Huang, Mengzhu; Zhang, Zhengsheng; Yang, Tianyu

2016-05-04

Foxtail millet [Setaria italica (L.) P. Beauv.], a crop of historical importance in China, has been adopted as a model crop for studying C-4 photosynthesis, stress biology and biofuel traits. Construction of a high density genetic map and identification of stable quantitative trait loci (QTL) lay the foundation for marker-assisted selection for agronomic traits and yield improvement. A total of 10598 SSR markers were developed according to the reference genome sequence of foxtail millet cultivar 'Yugu1'. A total of 1013 SSR markers showing polymorphism between Yugu1 and Longgu7 were used to genotype 167 individuals from a Yugu1 × Longgu7 F2 population, and a high density genetic map was constructed. The genetic map contained 1035 loci and spanned 1318.8 cM with an average distance of 1.27 cM between adjacent markers. Based on agronomic and yield traits identified in 2 years, 29 QTL were identified for 11 traits with combined analysis and single environment analysis. These QTL explained from 7.0 to 14.3 % of phenotypic variation. Favorable QTL alleles for peduncle length originated from Longgu7 whereas favorable alleles for the other traits originated from Yugu1 except for qLMS6.1. New SSR markers, a high density genetic map and QTL identified for agronomic and yield traits lay the ground work for functional gene mapping, map-based cloning and marker-assisted selection in foxtail millet.

Bone Mineral Density as a Marker of Cumulative Estrogen Exposure in Psychotic Disorder: A 3 Year Follow-Up Study.

PubMed

van der Leeuw, Christine; Peeters, Sanne; Domen, Patrick; van Kroonenburgh, Marinus; van Os, Jim; Marcelis, Machteld

2015-01-01

Altered estrogen-induced neuroprotection has been implicated in the etiology of psychotic disorders. Using bone mineral density as a marker of lifetime estrogen exposure, a longitudinal family study was conducted to discriminate between etiological mechanisms and secondary effects of disease and treatment. Dual X-ray absorptiometry scans were acquired twice, with an interval of 3 years, in 30 patients with psychotic disorder (male (M)/female (F): 24/6, mean age of 32 years at second measurement), 44 non-psychotic siblings of patients with a psychotic disorder (M/F: 26/18, mean age 32) and 27 controls (M/F: 7/20, mean age 35). Total bone mineral density, Z-scores and T-scores were measured in the lumbar spine and proximal femur. Associations between group and bone mineral density changes were investigated with multilevel random regression analyses. The effect of prolactin-raising antipsychotic medication was evaluated. (Increased risk of) psychotic disorder was not associated with disproportionate bone mineral density loss over a three year period. Instead, femoral bone mineral density measures appeared to decrease less in the patient versus control comparison (total BMD: B = 0.026, 95% CI 0.002 to 0.050, p = 0.037; Z-score: B = 0.224, 95% CI 0.035 to 0.412, p = 0.020; and T-score: B = 0.193, 95% CI 0.003 to 0.382, p = 0.046). Current or past use of a prolactin-raising antipsychotic medication was not associated with bone mineral density changes. In this small longitudinal study, there was no evidence of ongoing estrogen deficiency in psychotic disorder as there was no excessive loss of bone mineral density over a 3-year period in patients using antipsychotic medication.

Bone Mineral Density as a Marker of Cumulative Estrogen Exposure in Psychotic Disorder: A 3 Year Follow-Up Study

PubMed Central

van der Leeuw, Christine; Peeters, Sanne; Domen, Patrick; van Kroonenburgh, Marinus; van Os, Jim; Marcelis, Machteld

2015-01-01

Altered estrogen-induced neuroprotection has been implicated in the etiology of psychotic disorders. Using bone mineral density as a marker of lifetime estrogen exposure, a longitudinal family study was conducted to discriminate between etiological mechanisms and secondary effects of disease and treatment. Dual X-ray absorptiometry scans were acquired twice, with an interval of 3 years, in 30 patients with psychotic disorder (male (M)/female (F): 24/6, mean age of 32 years at second measurement), 44 non-psychotic siblings of patients with a psychotic disorder (M/F: 26/18, mean age 32) and 27 controls (M/F: 7/20, mean age 35). Total bone mineral density, Z-scores and T-scores were measured in the lumbar spine and proximal femur. Associations between group and bone mineral density changes were investigated with multilevel random regression analyses. The effect of prolactin-raising antipsychotic medication was evaluated. (Increased risk of) psychotic disorder was not associated with disproportionate bone mineral density loss over a three year period. Instead, femoral bone mineral density measures appeared to decrease less in the patient versus control comparison (total BMD: B = 0.026, 95% CI 0.002 to 0.050, p = 0.037; Z-score: B = 0.224, 95% CI 0.035 to 0.412, p = 0.020; and T-score: B = 0.193, 95% CI 0.003 to 0.382, p = 0.046). Current or past use of a prolactin-raising antipsychotic medication was not associated with bone mineral density changes. In this small longitudinal study, there was no evidence of ongoing estrogen deficiency in psychotic disorder as there was no excessive loss of bone mineral density over a 3-year period in patients using antipsychotic medication. PMID:26309037

Multiple reaction monitoring targeted LC-MS analysis of potential cell death marker proteins for increased bioprocess control.

PubMed

Albrecht, Simone; Kaisermayer, Christian; Reinhart, David; Ambrose, Monica; Kunert, Renate; Lindeberg, Anna; Bones, Jonathan

2018-05-01

The monitoring of protein biomarkers for the early prediction of cell stress and death is a valuable tool for process characterization and efficient biomanufacturing control. A representative set of six proteins, namely GPDH, PRDX1, LGALS1, CFL1, TAGLN2 and MDH, which were identified in a previous CHO-K1 cell death model using discovery LC-MS E was translated into a targeted liquid chromatography multiple reaction monitoring mass spectrometry (LC-MRM-MS) platform and verified. The universality of the markers was confirmed in a cell growth model for which three Chinese hamster ovary host cell lines (CHO-K1, CHO-S, CHO-DG44) were grown in batch culture in two different types of basal media. LC-MRM-MS was also applied to spent media (n = 39) from four perfusion biomanufacturing series. Stable isotope-labelled peptide analogues and a stable isotope-labelled monoclonal antibody were used for improved protein quantitation and simultaneous monitoring of the workflow reproducibility. Significant increases in protein concentrations were observed for all viability marker proteins upon increased dead cell numbers and allowed for discrimination of spent media with dead cell densities below and above 1 × 10 6  dead cells/mL which highlights the potential of the selected viability marker proteins in bioprocess control. Graphical abstract Overview of the LC-MRM-MS workflow for the determination of proteomic markers in conditioned media from the bioreactor that correlate with CHO cell death.

Omega-3 fatty acid supplement prevents development of intracranial atherosclerosis.

PubMed

Shen, Jiamei; Hafeez, Adam; Stevenson, James; Yang, Jianjie; Yin, Changbin; Li, Fengwu; Wang, Sainan; Du, Huishan; Ji, Xunming; Rafols, Jose A; Geng, Xiaokun; Ding, Yuchuan

2016-10-15

Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide and, in particular, has been implicated as a leading cause of recurrent ischemic stroke. We adapted a rat model of atherosclerosis to study brain intracranial atherosclerosis, and further investigated the effect of omega-3 fatty acids (O3FA) in attenuating development of ICAS. Adult male Sprague-Dawley rats were divided into control normal-cholesterol or high-cholesterol diet groups with or without O3FA for up to 6weeks. During the first 2weeks, NG-nitro-l-arginine methyl ester (l-NAME, 3mg/mL) was added to the drinking water of the high-cholesterol groups. The rats received supplementation with O3FA (5mg/kg/day) by gavages. Blood lipids including low density lipoprotein (LDL), cholesterol (CHO), triglycerides (TG) and high density lipoprotein (HDL) were measured at 3 and 6weeks. The lumen of middle cerebral artery (MCA) and the thickness of the vessel wall were assessed. Inflammatory molecular markers were assessed by Western blot. A high-cholesterol diet exhibited a significant increase in the classic blood markers (LDL, CHO, and TG) for atherosclerosis, as well as a decrease in HDL. These markers were found to be progressively more severe with time. Lumen stenosis and intimal thickening were increased in MCA. O3FA showed attenuation of blood lipids with an absence of morphological changes. O3FA significantly reduced the inflammatory marker CD68 in MCA and prevented monocyte chemotactic protein (MCP-1) and interferon-γ (IFN-γ) expression in the brain. O3FA similarly decreased inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6), markers affiliated with monocyte activity in atherosclerosis. Furthermore, O3FA significantly inhibited the expression of vascular cell adhesion molecule-1 (VCAM-1), a marker for endothelial activation. Lastly, O3FA increased ATP-binding cassette transporter A1 (ABCA1) protein expression via silent information regulator 1 (SIRT1) activation, thus increasing cholesterol efflux from macrophages to HDL. Long-term O3FA dietary supplementation prevents the development of intracranial atherosclerosis. This O3FA effect appears to be mediated by its prevention of macrophage infiltration into the vessel wall, therefore reducing inflammation and intimal thickening. While similar effects in humans need to be determined, O3FA dietary supplement shows promising results in the prevention of ICAS. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Body composition, cardiometabolic risk factors, physical activity, and inflammatory markers in premenopausal women after a 10-year follow-up: a MONET study.

PubMed

Razmjou, Sahar; Abdulnour, Joseph; Bastard, Jean-Philippe; Fellahi, Soraya; Doucet, Éric; Brochu, Martin; Lavoie, Jean-Marc; Rabasa-Lhoret, Rémi; Prud'homme, Denis

2018-01-01

Menopausal transition and postmenopause are usually associated with changes in body composition and a decrease in physical activity energy expenditure (PAEE). This study investigated body composition, cardiometabolic risk factors, PAEE, and inflammatory markers in premenopausal women after a 10-year follow-up. In all, 102 premenopausal women participated in the 5-year observational longitudinal Montreal Ottawa New Emerging Team (MONET) study. This present substudy included 48 participants (age: 60.0 ± 1.7 years; body mass index: 23.2 ± 2.2 kg/m) 6.0 ± 0.3 years after completion of the initial MONET study. Measures included body composition, waist circumference (WC), fasting glucose and insulin levels, insulin sensitivity (QUICKI model), plasma lipid levels, PAEE, and inflammatory markers. Compared with baseline measures of the MONET study, analyses revealed no significant increase in body weight, although there were significant increases in WC, fat mass (FM), % FM, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, haptoglobin, apolipoprotein B, ferritin, adiponectin, and soluble cluster of differentiation 14 (all P < 0.001) after the 10-year follow-up. However, significant decreases were observed for fat-free mass, PAEE, fasting glucose levels, interleukin-8 levels, and soluble tumor necrosis factor receptors 1 and 2 (sTNFR-1 and sTNFR-2) levels (all P < 0.05). To determine the effect of postmenopausal years, data were restructured based on final menstrual period (FMP), and one-way analyses of variance were performed.Waist circumference, % FM, total cholesterol, high-density lipoprotein cholesterol, apolipoprotein B, ferritin, adiponectin, and soluble cluster of differentiation 14 were higher in early and late postmenopausal periods in these women. sTNFR-1 and sTNFR-2 levels were higher at the FMP and early postmenopausal years as compared with the late postmenopausal periods. Finally, interleukin-8 levels were lower in years after FMP. The number of years elapsed since the FMP can affect body composition, cardiometabolic risk factors, and inflammatory markers in healthy premenopausal women going through menopausal transition and postmenopausal periods.

Gene Methylation and Cytological Atypia in Random Fine Needle Aspirates for Assessment of Breast Cancer Risk

PubMed Central

Hafeez, Sidra; Bujanda, Zoila Lopez; Chatterton, Robert T.; Jacobs, Lisa K.; Khouri, Nagi F.; Ivancic, David; Kenney, Kara; Shehata, Christina; Jeter, Stacie C.; Wolfman, Judith A.; Zalles, Carola M.; Huang, Peng

2016-01-01

Methods to determine individualized breast cancer risk lack sufficient sensitivity to select women most likely to benefit from preventive strategies. Alterations in DNA methylation occur early in breast cancer. We hypothesized that cancer-specific methylation markers could enhance breast cancer risk assessment. We evaluated 380 women without a history of breast cancer. We determined their menopausal status or menstrual cycle phase, risk of developing breast cancer (Gail model), and breast density, and obtained random fine needle aspiration (rFNA) samples for assessment of cytopathology and cumulative methylation index (CMI). Eight methylated gene markers were identified through whole genome methylation analysis and included novel and previously established breast cancer detection genes. We performed correlative and multivariate linear regression analyses to evaluate DNA methylation of a gene panel as a function of clinical factors associated with breast cancer risk. CMI and individual gene methylation were independent of age, menopausal status or menstrual phase, lifetime Gail risk score, and breast density. CMI and individual gene methylation for the eight genes increased significantly (p<0.001) with increasing cytological atypia. The findings were verified with multivariate analyses correcting for age, log (Gail), log (percent density), rFNA cell number and BMI. Our results demonstrate a significant association between cytological atypia and high CMI, which does not vary with menstrual phase or menopause and is independent of Gail risk and mammographic density. Thus CMI is an excellent candidate breast cancer risk biomarker, warranting larger prospective studies to establish its utility for cancer risk assessment. PMID:27261491

Genomic selection in plant breeding

USDA-ARS?s Scientific Manuscript database

Genomic selection (GS) is a method to predict the genetic value of selection candidates based on the genomic estimated breeding value (GEBV) predicted from high-density markers positioned throughout the genome. Unlike marker-assisted selection, the GEBV is based on all markers including both minor ...

Cardiac macrophages adopt profibrotic/M2 phenotype in infarcted hearts: Role of urokinase plasminogen activator.

PubMed

Carlson, Signe; Helterline, Deri; Asbe, Laura; Dupras, Sarah; Minami, Elina; Farris, Stephen; Stempien-Otero, April

2017-07-01

Macrophages (mac) that over-express urokinase plasminogen activator (uPA) adopt a profibrotic M2 phenotype in the heart in association with cardiac fibrosis. We tested the hypothesis that cardiac macs are M2 polarized in infarcted mouse and human hearts and that polarization is dependent on mac-derived uPA. Studies were performed using uninjured (UI) or infarcted (MI) hearts of uPA overexpressing (SR-uPA), uPA null, or nontransgenic littermate (Ntg) mice. At 7days post-infarction, cardiac mac were isolated, RNA extracted and M2 markers Arg1, YM1, and Fizz1 measured with qrtPCR. Histologic analysis for cardiac fibrosis, mac and myofibroblasts was performed at the same time-point. Cardiac macs were also isolated from Ntg hearts and RNA collected after primary isolation or culture with vehicle, IL-4 or plasmin and M2 marker expression measured. Cardiac tissue and blood was collected from humans with ischemic heart disease. Expression of M2 marker CD206 and M1 marker TNFalpha was measured. Macs from WT mice had increased expression of Arg1 and Ym1 following MI (41.3±6.5 and 70.3±36, fold change vs UI, n=8, P<0.007). There was significant up-regulation of cardiac mac Arg1 and YM1 with MI in both WT and uPA null mice (n=4-9 per genotype and condition). Treatment with plasmin increased expression of Arg1 and YM1 in cultured cardiac macs. Histologic analysis revealed increased density of activated fibroblasts and M2 macs in SR-uPA hearts post-infarction with associated increases in fibrosis. Cardiac macs isolated from human hearts with ischemic heart disease expressed increased levels of the M2 marker CD206 in comparison to blood-derived macs (4.9±1.3). Cardiac macs in mouse and human hearts adopt a M2 phenotype in association with fibrosis. Plasmin can induce an M2 phenotype in cardiac macs. However, M2 activation can occur in the heart in vivo in the absence of uPA indicating that alternative pathways to activate plasmin are present in the heart. Excess uPA promotes increased fibroblast density potentially via potentiating fibroblast migration or proliferation. Altering macrophage phenotype in the heart is a potential target to modify cardiac fibrosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

A framework linkage map of perennial ryegrass based on SSR markers

Treesearch

G.P. Gill; P.L. Wilcox; D.J. Whittaker; R.A. Winz; P. Bickerstaff; Craig E. Echt; J. Kent; M.O. Humphreys; K.M. Elborough; R.C. Gardner

2006-01-01

A moderate-density linkage map for Lolium perenne L. has been constructed based on 376 simple sequence repeat (SSR) markers. Approximately one third ( 124) of the SSR markers were developed from GeneThresher libraries that preferentially select genomic DNA clones from the gene-rich unmethylated portion of the genome. The remaining SSR marker loci...

Single Nucleotide Polymorphism Markers for Genetic Mapping in Drosophila melanogaster

PubMed Central

Hoskins, Roger A.; Phan, Alexander C.; Naeemuddin, Mohammed; Mapa, Felipa A.; Ruddy, David A.; Ryan, Jessica J.; Young, Lynn M.; Wells, Trent; Kopczynski, Casey; Ellis, Michael C.

2001-01-01

For nearly a century, genetic analysis in Drosophila melanogaster has been a powerful tool for analyzing gene function, yet Drosophila lacks the molecular genetic mapping tools that recently have revolutionized human, mouse, and plant genetics. Here, we describe the systematic characterization of a dense set of molecular markers in Drosophila by using a sequence tagged site-based physical map of the genome. We identify 474 biallelic markers in standard laboratory strains of Drosophila that span the genome. Most of these markers are single nucleotide polymorphisms and sequences for these variants are provided in an accessible format. The average density of the new markers is one per 225 kb on the autosomes and one per megabase on the X chromosome. We include in this survey a set of P-element strains that provide additional use for high-resolution mapping. We show one application of the new markers in a simple set of crosses to map a mutation in the hedgehog gene to an interval of <1 Mb. This new map resource significantly increases the efficiency and resolution of recombination mapping and will be of immediate value to the Drosophila research community. PMID:11381036

A High Density Consensus Genetic Map of Tetraploid Cotton That Integrates Multiple Component Maps through Molecular Marker Redundancy Check

PubMed Central

Blenda, Anna; Fang, David D.; Rami, Jean-François; Garsmeur, Olivier; Luo, Feng; Lacape, Jean-Marc

2012-01-01

A consensus genetic map of tetraploid cotton was constructed using six high-density maps and after the integration of a sequence-based marker redundancy check. Public cotton SSR libraries (17,343 markers) were curated for sequence redundancy using 90% as a similarity cutoff. As a result, 20% of the markers (3,410) could be considered as redundant with some other markers. The marker redundancy information had been a crucial part of the map integration process, in which the six most informative interspecific Gossypium hirsutum×G. barbadense genetic maps were used for assembling a high density consensus (HDC) map for tetraploid cotton. With redundant markers being removed, the HDC map could be constructed thanks to the sufficient number of collinear non-redundant markers in common between the component maps. The HDC map consists of 8,254 loci, originating from 6,669 markers, and spans 4,070 cM, with an average of 2 loci per cM. The HDC map presents a high rate of locus duplications, as 1,292 markers among the 6,669 were mapped in more than one locus. Two thirds of the duplications are bridging homoeologous AT and DT chromosomes constitutive of allopolyploid cotton genome, with an average of 64 duplications per AT/DT chromosome pair. Sequences of 4,744 mapped markers were used for a mutual blast alignment (BBMH) with the 13 major scaffolds of the recently released Gossypium raimondii genome indicating high level of homology between the diploid D genome and the tetraploid cotton genetic map, with only a few minor possible structural rearrangements. Overall, the HDC map will serve as a valuable resource for trait QTL comparative mapping, map-based cloning of important genes, and better understanding of the genome structure and evolution of tetraploid cotton. PMID:23029214

Biomarkers of Cell Senescence Assessed by Imaging Cytometry

PubMed Central

Zhao, Hong; Darzynkiewicz, Zbigniew

2012-01-01

The characteristic features of senescent cells such as their “flattened” appearance, enlarged nuclei and low saturation density at the plateau phase of cell growth, can be conveniently measured by image-assisted d cytometry such as provided by the laser scanning cytometry (LSC). The “flattening” of senescent cells is reflected by the decline in local density of staining (intensity of maximal pixel) of DNA-associated fluorescence [4,6-diamidino-2- phenylindole (DAPI)] paralleled by an increase in nuclear size (area). Thus, the ratio of the maximal pixel of DAPI fluorescence per nucleus to the nuclear area provides a very sensitive morphometric biomarker of “depth” of senescence, which progressively declines during induction of senescence. Also recorded is cellular DNA content revealing cell cycle phase, as well as the saturation cell density at plateau phase of growth, which is dramatically decreased in cultures of senescent cells. Concurrent immunocytochemical analysis of expression of p21WAF1, p16INK4a or p27KIP1 cyclin kinase inhibitor provides additional markers of senescence. These biomarker indices can be expressed in quantitative terms (“senescence indices”) as a fraction of the same markers of the exponentially growing cells in control cultures. PMID:23296652

Bone Metabolism on ISS Missions

NASA Technical Reports Server (NTRS)

Smith, S. M.; Heer, M. A.; Shackelford, L. C.; Zwart, S. R.

2014-01-01

Spaceflight-induced bone loss is associated with increased bone resorption (1, 2), and either unchanged or decreased rates of bone formation. Resistive exercise had been proposed as a countermeasure, and data from bed rest supported this concept (3). An interim resistive exercise device (iRED) was flown for early ISS crews. Unfortunately, the iRED provided no greater bone protection than on missions where only aerobic and muscular endurance exercises were available (4, 5). In 2008, the Advanced Resistive Exercise Device (ARED), a more robust device with much greater resistance capability, (6, 7) was launched to the ISS. Astronauts who had access to ARED, coupled with adequate energy intake and vitamin D status, returned from ISS missions with bone mineral densities virtually unchanged from preflight (7). Bone biochemical markers showed that while the resistive exercise and adequate energy consumption did not mitigate the increased bone resorption, bone formation was increased (7, 8). The typical drop in circulating parathyroid hormone did not occur in ARED crewmembers. In 2014, an updated look at the densitometry data was published. This study confirmed the initial findings with a much larger set of data. In 42 astronauts (33 male, 9 female), the bone mineral density response to flight was the same for men and women (9), and those with access to the ARED did not have the typical decrease in bone mineral density that was observed in early ISS crewmembers with access to the iRED (Figure 1) (7). Biochemical markers of bone formation and resorption responded similarly in men and women. These data are encouraging, and represent the first in-flight evidence in the history of human space flight that diet and exercise can maintain bone mineral density on long-duration missions. However, the maintenance of bone mineral density through bone remodeling, that is, increases in both resorption and formation, may yield a bone with strength characteristics different from those that existed before space flight. Studies to assess bone strength after flight are underway at NASA, to better understand the results of bone remodeling. Studies are also underway to evaluate optimized exercise protocols and nutritional countermeasures. Regardless, there is clear evidence of progress being made to protect bone during spaceflight.

Physiological proteins in resource-limited herbivores experiencing a population die-off

NASA Astrophysics Data System (ADS)

Garnier, R.; Bento, A. I.; Hansen, C.; Pilkington, J. G.; Pemberton, J. M.; Graham, A. L.

2017-08-01

Nutrient availability is predicted to interact with herbivore population densities. Competition for low quality food at high density may reduce summer food intake, and in turn winter survival. Conversely, low population density may favor physiological recovery through better access to better quality spring forage. Here, we take advantage of the long-term study of the Soay sheep population of St. Kilda (Scotland) to measure plasma protein markers and immunity in two consecutive summers with contrasting population densities. We show that, following a winter die-off resulting in a shift to low population density, albumin and total proteins increased, but only in adult sheep. The effect was not solely attributable to selective disappearance of malnourished sheep. Similarly, the concentration of antibodies was higher following the die-off, potentially indicating recovery of immune function. Overall, our results are consistent with the physiological recovery of surviving individuals after a harsh winter.

A High-Density Consensus Map of Common Wheat Integrating Four Mapping Populations Scanned by the 90K SNP Array

PubMed Central

Wen, Weie; He, Zhonghu; Gao, Fengmei; Liu, Jindong; Jin, Hui; Zhai, Shengnan; Qu, Yanying; Xia, Xianchun

2017-01-01

A high-density consensus map is a powerful tool for gene mapping, cloning and molecular marker-assisted selection in wheat breeding. The objective of this study was to construct a high-density, single nucleotide polymorphism (SNP)-based consensus map of common wheat (Triticum aestivum L.) by integrating genetic maps from four recombinant inbred line populations. The populations were each genotyped using the wheat 90K Infinium iSelect SNP assay. A total of 29,692 SNP markers were mapped on 21 linkage groups corresponding to 21 hexaploid wheat chromosomes, covering 2,906.86 cM, with an overall marker density of 10.21 markers/cM. Compared with the previous maps based on the wheat 90K SNP chip detected 22,736 (76.6%) of the SNPs with consistent chromosomal locations, whereas 1,974 (6.7%) showed different chromosomal locations, and 4,982 (16.8%) were newly mapped. Alignment of the present consensus map and the wheat expressed sequence tags (ESTs) Chromosome Bin Map enabled assignment of 1,221 SNP markers to specific chromosome bins and 819 ESTs were integrated into the consensus map. The marker orders of the consensus map were validated based on physical positions on the wheat genome with Spearman rank correlation coefficients ranging from 0.69 (4D) to 0.97 (1A, 4B, 5B, and 6A), and were also confirmed by comparison with genetic position on the previously 40K SNP consensus map with Spearman rank correlation coefficients ranging from 0.84 (6D) to 0.99 (6A). Chromosomal rearrangements reported previously were confirmed in the present consensus map and new putative rearrangements were identified. In addition, an integrated consensus map was developed through the combination of five published maps with ours, containing 52,607 molecular markers. The consensus map described here provided a high-density SNP marker map and a reliable order of SNPs, representing a step forward in mapping and validation of chromosomal locations of SNPs on the wheat 90K array. Moreover, it can be used as a reference for quantitative trait loci (QTL) mapping to facilitate exploitation of genes and QTL in wheat breeding. PMID:28848588

Genic Microsatellite Markers in Brassica rapa: Development, Characterization, Mapping, and Their Utility in Other Cultivated and Wild Brassica Relatives

PubMed Central

Ramchiary, Nirala; Nguyen, Van Dan; Li, Xiaonan; Hong, Chang Pyo; Dhandapani, Vignesh; Choi, Su Ryun; Yu, Ge; Piao, Zhong Yun; Lim, Yong Pyo

2011-01-01

Genic microsatellite markers, also known as functional markers, are preferred over anonymous markers as they reveal the variation in transcribed genes among individuals. In this study, we developed a total of 707 expressed sequence tag-derived simple sequence repeat markers (EST-SSRs) and used for development of a high-density integrated map using four individual mapping populations of B. rapa. This map contains a total of 1426 markers, consisting of 306 EST-SSRs, 153 intron polymorphic markers, 395 bacterial artificial chromosome-derived SSRs (BAC-SSRs), and 572 public SSRs and other markers covering a total distance of 1245.9 cM of the B. rapa genome. Analysis of allelic diversity in 24 B. rapa germplasm using 234 mapped EST-SSR markers showed amplification of 2 alleles by majority of EST-SSRs, although amplification of alleles ranging from 2 to 8 was found. Transferability analysis of 167 EST-SSRs in 35 species belonging to cultivated and wild brassica relatives showed 42.51% (Sysimprium leteum) to 100% (B. carinata, B. juncea, and B. napus) amplification. Our newly developed EST-SSRs and high-density linkage map based on highly transferable genic markers would facilitate the molecular mapping of quantitative trait loci and the positional cloning of specific genes, in addition to marker-assisted selection and comparative genomic studies of B. rapa with other related species. PMID:21768136

Genomic selection in plant breeding.

PubMed

Newell, Mark A; Jannink, Jean-Luc

2014-01-01

Genomic selection (GS) is a method to predict the genetic value of selection candidates based on the genomic estimated breeding value (GEBV) predicted from high-density markers positioned throughout the genome. Unlike marker-assisted selection, the GEBV is based on all markers including both minor and major marker effects. Thus, the GEBV may capture more of the genetic variation for the particular trait under selection.

Postmortem evidence of cerebral inflammation in schizophrenia: a systematic review

PubMed Central

Trépanier, M O; Hopperton, K E; Mizrahi, R; Mechawar, N; Bazinet, R P

2016-01-01

Schizophrenia is a psychiatric disorder which has a lifetime prevalence of ~1%. Multiple candidate mechanisms have been proposed in the pathogenesis of schizophrenia. One such mechanism is the involvement of neuroinflammation. Clinical studies, including neuroimaging, peripheral biomarkers and randomized control trials, have suggested the presence of neuroinflammation in schizophrenia. Many studies have also measured markers of neuroinflammation in postmortem brain samples from schizophrenia patients. The objective of this study was to conduct a systematic search of the literature on neuroinflammation in postmortem brains of schizophrenia patients indexed in MEDLINE, Embase and PsycINFO. Databases were searched up until 20th March 2016 for articles published on postmortem brains in schizophrenia evaluating microglia, astrocytes, glia, cytokines, the arachidonic cascade, substance P and other markers of neuroinflammation. Two independent reviewers extracted the data. Out of 5385 articles yielded by the search, 119 articles were identified that measured neuroinflammatory markers in schizophrenic postmortem brains. Glial fibrillary acidic protein expression was elevated, lower or unchanged in 6, 6 and 21 studies, respectively, and similar results were obtained for glial cell densities. On the other hand, microglial markers were increased, lower or unchanged in schizophrenia in 11, 3 and 8 studies, respectively. Results were variable across all other markers, but SERPINA3 and IFITM were consistently increased in 4 and 5 studies, respectively. Despite the variability, some studies evaluating neuroinflammation in postmortem brains in schizophrenia suggest an increase in microglial activity and other markers such as SERPINA3 and IFITM. Variability across studies is partially explained by multiple factors including brain region evaluated, source of the brain, diagnosis, age at time of death, age of onset and the presence of suicide victims in the cohort. PMID:27271499

Agomelatine (S20098) modulates the expression of cytoskeletal microtubular proteins, synaptic markers and BDNF in the rat hippocampus, amygdala and PFC.

PubMed

Ladurelle, Nataly; Gabriel, Cecilia; Viggiano, Adela; Mocaër, Elisabeth; Baulieu, Etienne E; Bianchi, Massimiliano

2012-06-01

Agomelatine is described as a novel and clinical effective antidepressant drug with melatonergic (MT(1)/MT(2)) agonist and 5-HT(2C) receptor antagonist properties. Previous studies suggest that modulation of neuronal plasticity and microtubule dynamics may be involved in the treatment of depression. The present study investigated the effects of agomelatine on microtubular, synaptic and brain-derived neurotrophic factor (BDNF) proteins in selected rat brain regions. Adult male rats received agomelatine (40 mg/kg i.p.) once a day for 22 days. The pro-cognitive effect of agomelatine was tested in the novel object recognition task and antidepressant activity in the forced swimming test. Microtubule dynamics markers, microtubule-associated protein type 2 (MAP-2), phosphorylated MAP-2, synaptic markers [synaptophysin, postsynaptic density-95 (PSD-95) and spinophilin] and BDNF were measured by Western blot in the hippocampus, amygdala and prefrontal cortex (PFC). Agomelatine exerted pro-cognitive and antidepressant activity and induced molecular changes in the brain areas examined. Agomelatine enhanced microtubule dynamics in the hippocampus and to a higher magnitude in the amygdala. By contrast, in the PFC, a decrease in microtubule dynamics was observed. Spinophilin (dendritic spines marker) was decreased, and BDNF increased in the hippocampus. Synaptophysin (presynaptic) and spinophilin were increased in the PFC and amygdala, while PSD-95 (postsynaptic marker) was increased in the amygdala, consistent with the phenomena of synaptic remodelling. Agomelatine modulates cytoskeletal microtubule dynamics and synaptic markers. This may play a role in its pharmacological behavioural effects and may result from the melatonergic agonist and 5-HT(2C) antagonist properties of the compound.

High-density genetic map construction and QTLs identification for plant height in white jute (Corchorus capsularis L.) using specific locus amplified fragment (SLAF) sequencing.

PubMed

Tao, Aifen; Huang, Long; Wu, Guifen; Afshar, Reza Keshavarz; Qi, Jianmin; Xu, Jiantang; Fang, Pingping; Lin, Lihui; Zhang, Liwu; Lin, Peiqing

2017-05-08

Genetic mapping and quantitative trait locus (QTL) detection are powerful methodologies in plant improvement and breeding. White jute (Corchorus capsularis L.) is an important industrial raw material fiber crop because of its elite characteristics. However, construction of a high-density genetic map and identification of QTLs has been limited in white jute due to a lack of sufficient molecular markers. The specific locus amplified fragment sequencing (SLAF-seq) strategy combines locus-specific amplification and high-throughput sequencing to carry out de novo single nuclear polymorphism (SNP) discovery and large-scale genotyping. In this study, SLAF-seq was employed to obtain sufficient markers to construct a high-density genetic map for white jute. Moreover, with the development of abundant markers, genetic dissection of fiber yield traits such as plant height was also possible. Here, we present QTLs associated with plant height that were identified using our newly constructed genetic linkage groups. An F 8 population consisting of 100 lines was developed. In total, 69,446 high-quality SLAFs were detected of which 5,074 SLAFs were polymorphic; 913 polymorphic markers were used for the construction of a genetic map. The average coverage for each SLAF marker was 43-fold in the parents, and 9.8-fold in each F 8 individual. A linkage map was constructed that contained 913 SLAFs on 11 linkage groups (LGs) covering 1621.4 cM with an average density of 1.61 cM per locus. Among the 11 LGs, LG1 was the largest with 210 markers, a length of 406.34 cM, and an average distance of 1.93 cM between adjacent markers. LG11 was the smallest with only 25 markers, a length of 29.66 cM, and an average distance of 1.19 cM between adjacent markers. 'SNP_only' markers accounted for 85.54% and were the predominant markers on the map. QTL mapping based on the F 8 phenotypes detected 11 plant height QTLs including one major effect QTL across two cultivation locations, with each QTL accounting for 4.14-15.63% of the phenotypic variance. To our knowledge, the linkage map constructed here is the densest one available to date for white jute. This analysis also identified the first QTL in white jute. The results will provide an important platform for gene/QTL mapping, sequence assembly, genome comparisons, and marker-assisted selection breeding for white jute.

Disease-related microglia heterogeneity in the hippocampus of Alzheimer's disease, dementia with Lewy bodies, and hippocampal sclerosis of aging.

PubMed

Bachstetter, Adam D; Van Eldik, Linda J; Schmitt, Frederick A; Neltner, Janna H; Ighodaro, Eseosa T; Webster, Scott J; Patel, Ela; Abner, Erin L; Kryscio, Richard J; Nelson, Peter T

2015-05-23

Neuropathological, genetic, and biochemical studies have provided support for the hypothesis that microglia participate in Alzheimer's disease (AD) pathogenesis. Despite the extensive characterization of AD microglia, there are still many unanswered questions, and little is known about microglial morphology in other common forms of age-related dementia: particularly, dementia with Lewy bodies (DLB) and hippocampal sclerosis of aging (HS-Aging). In addition, no prior studies have attempted to compare and contrast the microglia morphology in the hippocampus of various neurodegenerative conditions. Here we studied cases with pathologically-confirmed AD (n = 7), HS-Aging (n = 7), AD + HS-aging (n = 4), DLB (n = 12), and normal (cognitively intact) controls (NC) (n = 9) from the University of Kentucky Alzheimer's Disease Center autopsy cohort. We defined five microglia morphological phenotypes in the autopsy samples: ramified, hypertrophic, dystrophic, rod-shaped, and amoeboid. The Aperio ScanScope digital neuropathological tool was used along with two well-known microglial markers: IBA1 (a marker for both resting and activated microglia) and CD68 (a lysosomal marker in macrophages/microglia associated with phagocytic cells). Hippocampal staining analyses included studies of subregions within the hippocampal formation and nearby white matter. Using these tools and methods, we describe variation in microglial characteristics that show some degree of disease specificity, including, (1) increased microglia density and number in HS-aging and AD + HS-aging; (2) low microglia density in DLB; (3) increased number of dystrophic microglia in HS-aging; and (4) increased proportion of dystrophic to all microglia in DLB. We conclude that variations in morphologies among microglial cells, and cells of macrophage lineage, can help guide future work connecting neuroinflammatory mechanisms with specific neurodegenerative disease subtypes.

Possible therapeutic potential of berberine in diabetic osteopathy.

PubMed

Rahigude, A B; Kaulaskar, S V; Bhutada, P S

2012-10-01

Diabetic osteopathy is a complication that leads to decreased bone mineral density, bone formation and having high risk of fractures that heals slowly. Diabetic osteopathy is a result of increase in osteoclastogenesis and decrease in osteoblastogenesis. Various factors viz., oxidative stress, increased inflammatory markers, PPAR-γ activation in osteoblast, activation of apoptotic pathway, increased glucose levels and inhibitory effect on parathyroid hormone etc. are mainly responsible for decreased bone mineral density. Berberine is an isoquinoline alkaloid widely used in Asian countries as a traditional medicine. Berberine is extensively reported to be an antioxidant, anti-inflammatory, antidiabetic, and having potential to treat diabetic complications and glucocorticoid induced osteoporosis. The osteoclastogenesis decreasing property of berberine can be hypothesized for inhibiting diabetic osteopathy. In addition, chronic treatment of berberine will be helpful for increasing the osteoblastic activity and expression of the modulators that affect osteoblastic differentiation. The apoptotic pathways stimulated due to increased inflammatory markers and nucleic acid damages could be reduced due to berberine. Another important consideration that berberine is having stimulatory effect on glucagon like peptide release and insulin sensitization that will be helpful for decreasing glucose levels and therefore, may exerts osteogenesis. Thiazolidinediones show bone loss due to activation of PPAR-γ in osteoblasts, whereas berberine stimulates PPAR-γ only in adipocytes and not in osteoblasts, and therefore the decreased bone loss due to use of thiazolidinediones may not be observed in berberine treatment conditions. Berberine decreases the advanced glycation end-products (AGE) formation in diabetic condition which will be ultimately helpful to decrease the stiffness of collagen fibers due to AGE-induced cross linking. Lastly, it is also reported that berberine has inhibitory effect on parathyroid hormone and enhances marker genes like osteocalcin, which are responsible for the osteoblastic activity. From these evidences, we hypothesized that berberine may have potential in the treatment of diabetic osteopathy. Copyright © 2012 Elsevier Ltd. All rights reserved.

Increased meal frequency attenuates fat-free mass losses and some markers of health status with a portion-controlled weight loss diet.

PubMed

Alencar, Michelle K; Beam, Jason R; McCormick, James J; White, Ailish C; Salgado, Roy M; Kravitz, Len R; Mermier, Christine M; Gibson, Ann L; Conn, Carole A; Kolkmeyer, Deborah; Ferraro, Robert T; Kerksick, Chad M

2015-05-01

Increased meal frequency (MF) may be associated with improvements in blood markers of health and body composition during weight loss; however, this claim has not been validated. The purpose of the study was to determine if either a 2-meal (2 MF) or 6-meal frequency (6 MF) regimen can improve body composition and blood-based markers of health while consuming a portion-controlled equihypocaloric diet. Eleven (N=11) obese women (52 ± 7 years, 101.7 ± 22.6 kg, 39.1 ± 7.6 kg/m(2)) were randomized into treatment condition (2 MF or 6 MF) for 2 weeks, completed a 2-week washout, and alternated treatment conditions. In pre/post fashion, changes in body composition, glucose, insulin, and lipid components were measured in response to a test meal. Body mass was successfully lost (P ≤ .05) under both feeding regimens (2 MF: -2.8 ± 1.5 vs 6 MF: -1.9 ± 1.5 kg). Altering MF did not impact glucose, insulin, total cholesterol, or low-density lipoprotein cholesterol (P>.05). On average, fat-free mass (FFM) decreased by -3.3% ± 2.6% following the 2 MF condition and, on average, increased by 1.2% ± 1.7% following the 6 MF condition (P ≤ .05). Fasting high-density lipoprotein cholesterol (HDL-C) percentage increased during the 2 MF condition; this was significantly greater than that in the 6 MF condition (1.3% ± 12.2% vs 0.12% ± 10.3%) (P ≤ .05). Overall, reductions in MF (2 MF) were associated with improved HDL-C levels; but the clinical significance is not clear. Alternatively, increased MF (6 MF) did appear to favorably preserve FFM during weight loss. In conclusion, caloric restriction was effective in reducing body mass and attenuating FFM changes in body composition; however, glucose, insulin, and lipid metabolism had no significant differences between MF. Copyright © 2015 Elsevier Inc. All rights reserved.

One year soy protein supplementation has positive effects on bone formation markers but not bone density in postmenopausal women.

PubMed

Arjmandi, Bahram H; Lucas, Edralin A; Khalil, Dania A; Devareddy, Latha; Smith, Brenda J; McDonald, Jennifer; Arquitt, Andrea B; Payton, Mark E; Mason, Claudia

2005-02-23

Although soy protein and its isoflavones have been reported to reduce the risk of osteoporosis in peri- and post-menopausal women, most of these studies are of short duration (i.e. six months). The objective of this study was to examine if one year consumption of soy-containing foods (providing 25 g protein and 60 mg isoflavones) exerts beneficial effects on bone in postmenopausal women. Eighty-seven eligible postmenopausal women were randomly assigned to consume soy or control foods daily for one year. Bone mineral density (BMD) and bone mineral content (BMC) of the whole body, lumbar (L1-L4), and total hip were measured using dual energy x-ray absorptiometry at baseline and after one year. Blood and urine markers of bone metabolism were also assessed. Sixty-two subjects completed the one-year long study. Whole body and lumbar BMD and BMC were significantly decreased in both the soy and control groups. However, there were no significant changes in total hip BMD and BMC irrespective of treatment. Both treatments positively affected markers of bone formation as indicated by increased serum bone-specific alkaline phosphatase (BSAP) activity, insulin-like growth factor-I (IGF-I), and osteocalcin (BSAP: 27.8 and 25.8%, IGF-I: 12.8 and 26.3%, osteocalcin: 95.2 and 103.4% for control and soy groups, respectively). Neither of the protein supplements had any effect on urinary deoxypyridinoline excretion, a marker of bone resorption. Our findings suggest that although one year supplementation of 25 g protein per se positively modulated markers of bone formation, this amount of protein was unable to prevent lumbar and whole body bone loss in postmenopausal women.

Identification of QTLs associated with oil content in a high-oil Brassica napus cultivar and construction of a high-density consensus map for QTLs comparison in B. napus.

PubMed

Wang, Xiaodong; Wang, Hao; Long, Yan; Li, Dianrong; Yin, Yongtai; Tian, Jianhua; Chen, Li; Liu, Liezhao; Zhao, Weiguo; Zhao, Yajun; Yu, Longjiang; Li, Maoteng

2013-01-01

Increasing seed oil content is one of the most important goals in breeding of rapeseed (B. napus L.). To dissect the genetic basis of oil content in B. napus, a large and new double haploid (DH) population containing 348 lines was obtained from a cross between 'KenC-8' and 'N53-2', two varieties with >10% difference in seed oil content, and this population was named the KN DH population. A genetic linkage map consisting of 403 markers was constructed, which covered a total length of 1783.9 cM with an average marker interval of 4.4 cM. The KN DH population was phenotyped in eight natural environments and subjected to quantitative trait loci (QTL) analysis for oil content. A total of 63 identified QTLs explaining 2.64-17.88% of the phenotypic variation were identified, and these QTLs were further integrated into 24 consensus QTLs located on 11 chromosomes using meta-analysis. A high-density consensus map with 1335 marker loci was constructed by combining the KN DH map with seven other published maps based on the common markers. Of the 24 consensus QTLs in the KN DH population, 14 were new QTLs including five new QTLs in A genome and nine in C genome. The analysis revealed that a larger population with significant differences in oil content gave a higher power detecting new QTLs for oil content, and the construction of the consensus map provided a new clue for comparing the QTLs detected in different populations. These findings enriched our knowledge of QTLs for oil content and should be a potential in marker-assisted breeding of B. napus.

Identification of QTLs Associated with Oil Content in a High-Oil Brassica napus Cultivar and Construction of a High-Density Consensus Map for QTLs Comparison in B. napus

PubMed Central

Long, Yan; Li, Dianrong; Yin, Yongtai; Tian, Jianhua; Chen, Li; Liu, Liezhao; Zhao, Weiguo; Zhao, Yajun; Yu, Longjiang; Li, Maoteng

2013-01-01

Increasing seed oil content is one of the most important goals in breeding of rapeseed (B. napus L.). To dissect the genetic basis of oil content in B. napus, a large and new double haploid (DH) population containing 348 lines was obtained from a cross between ‘KenC-8’ and ‘N53-2’, two varieties with >10% difference in seed oil content, and this population was named the KN DH population. A genetic linkage map consisting of 403 markers was constructed, which covered a total length of 1783.9 cM with an average marker interval of 4.4 cM. The KN DH population was phenotyped in eight natural environments and subjected to quantitative trait loci (QTL) analysis for oil content. A total of 63 identified QTLs explaining 2.64–17.88% of the phenotypic variation were identified, and these QTLs were further integrated into 24 consensus QTLs located on 11 chromosomes using meta-analysis. A high-density consensus map with 1335 marker loci was constructed by combining the KN DH map with seven other published maps based on the common markers. Of the 24 consensus QTLs in the KN DH population, 14 were new QTLs including five new QTLs in A genome and nine in C genome. The analysis revealed that a larger population with significant differences in oil content gave a higher power detecting new QTLs for oil content, and the construction of the consensus map provided a new clue for comparing the QTLs detected in different populations. These findings enriched our knowledge of QTLs for oil content and should be a potential in marker-assisted breeding of B. napus. PMID:24312482

Circulating insulin-like growth factor-I, insulin-like growth factor binding protein-3 and terminal duct lobular unit involution of the breast: a cross-sectional study of women with benign breast disease.

PubMed

Horne, Hisani N; Sherman, Mark E; Pfeiffer, Ruth M; Figueroa, Jonine D; Khodr, Zeina G; Falk, Roni T; Pollak, Michael; Patel, Deesha A; Palakal, Maya M; Linville, Laura; Papathomas, Daphne; Geller, Berta; Vacek, Pamela M; Weaver, Donald L; Chicoine, Rachael; Shepherd, John; Mahmoudzadeh, Amir Pasha; Wang, Jeff; Fan, Bo; Malkov, Serghei; Herschorn, Sally; Hewitt, Stephen M; Brinton, Louise A; Gierach, Gretchen L

2016-02-18

Terminal duct lobular units (TDLUs) are the primary structures from which breast cancers and their precursors arise. Decreased age-related TDLU involution and elevated mammographic density are both correlated and independently associated with increased breast cancer risk, suggesting that these characteristics of breast parenchyma might be linked to a common factor. Given data suggesting that increased circulating levels of insulin-like growth factors (IGFs) factors are related to reduced TDLU involution and increased mammographic density, we assessed these relationships using validated quantitative methods in a cross-sectional study of women with benign breast disease. Serum IGF-I, IGFBP-3 and IGF-I:IGFBP-3 molar ratios were measured in 228 women, ages 40-64, who underwent diagnostic breast biopsies yielding benign diagnoses at University of Vermont affiliated centers. Biopsies were assessed for three separate measures inversely related to TDLU involution: numbers of TDLUs per unit of tissue area ("TDLU count"), median TDLU diameter ("TDLU span"), and number of acini per TDLU ("acini count"). Regression models, stratified by menopausal status and adjusted for potential confounders, were used to assess the associations of TDLU count, median TDLU span and median acini count per TDLU with tertiles of circulating IGFs. Given that mammographic density is associated with both IGF levels and breast cancer risk, we also stratified these associations by mammographic density. Higher IGF-I levels among postmenopausal women and an elevated IGF-I:IGFBP-3 ratio among all women were associated with higher TDLU counts, a marker of decreased lobular involution (P-trend = 0.009 and <0.0001, respectively); these associations were strongest among women with elevated mammographic density (P-interaction <0.01). Circulating IGF levels were not significantly associated with TDLU span or acini count per TDLU. These results suggest that elevated IGF levels may define a sub-group of women with high mammographic density and limited TDLU involution, two markers that have been related to increased breast cancer risk. If confirmed in prospective studies with cancer endpoints, these data may suggest that evaluation of IGF signaling and its downstream effects may have value for risk prediction and suggest strategies for breast cancer chemoprevention through inhibition of the IGF system.

High-density SNP genotyping array for hexaploid wheat and its secondary and tertiary gene pool.

PubMed

Winfield, Mark O; Allen, Alexandra M; Burridge, Amanda J; Barker, Gary L A; Benbow, Harriet R; Wilkinson, Paul A; Coghill, Jane; Waterfall, Christy; Davassi, Alessandro; Scopes, Geoff; Pirani, Ali; Webster, Teresa; Brew, Fiona; Bloor, Claire; King, Julie; West, Claire; Griffiths, Simon; King, Ian; Bentley, Alison R; Edwards, Keith J

2016-05-01

In wheat, a lack of genetic diversity between breeding lines has been recognized as a significant block to future yield increases. Species belonging to bread wheat's secondary and tertiary gene pools harbour a much greater level of genetic variability, and are an important source of genes to broaden its genetic base. Introgression of novel genes from progenitors and related species has been widely employed to improve the agronomic characteristics of hexaploid wheat, but this approach has been hampered by a lack of markers that can be used to track introduced chromosome segments. Here, we describe the identification of a large number of single nucleotide polymorphisms that can be used to genotype hexaploid wheat and to identify and track introgressions from a variety of sources. We have validated these markers using an ultra-high-density Axiom(®) genotyping array to characterize a range of diploid, tetraploid and hexaploid wheat accessions and wheat relatives. To facilitate the use of these, both the markers and the associated sequence and genotype information have been made available through an interactive web site. © 2015 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Four-year follow-up of pregnancy-associated osteoporosis: a case report.

PubMed

Takahashi, Naoto; Arai, Itaru; Kayama, Satoru; Ichiji, Kenji; Fukuda, Hironari; Handa, Jun-Ichi; Konno, Shin-Ichi

2014-01-01

A 22-year-old woman presented with complaints of severe pain in a wide region of the thoracolumbar spine. She developed severe pain in the thoracolumbar spine region 2 months after her first delivery and was referred 1 month later. A lateral thoracic X-ray showed depressed degenerative vertebrae (T7, T9). One month after the initial examination, thoracic sagittal magnetic resonance imaging showed low intensity areas on T1-weighted imaging and iso-high intensity areas on T2-weighted imaging at T5, 7, 8, 9 and 11. Bone mineral density measured by ultrasound was low (%YAM 76%). The bone metabolic markers were high, suggesting accelerated osteoclast activity. These findings prompted a diagnosis of pregnancy-associated osteoporosis. She was asked to stop breastfeeding and to wear a lumbar brace, and treatment with nutritional calcium, activated vitamin D3, and risedronate sodium was started. Her low back pain almost disappeared after treatment. Bone metabolic markers showed normalization 8 months after the initial examination. Risedronate sodium was stopped 2 years and 2 months after the initial examination. Teriparatide treatment was started because her bone mineral density remained low; however, the osteoblast marker P1NP was not increased 5 months after the start of teriparatide treatment.

Decreased osteoprotegerin and increased bone turnover in young female patients with major depressive disorder and a lifetime history of anorexia nervosa.

PubMed

Kahl, Kai G; Rudolf, Sebastian; Dibbelt, Leif; Stoeckelhuber, Beate M; Gehl, Hans-Björn; Hohagen, Fritz; Schweiger, Ulrich

2005-04-01

Low bone mineral density (BMD) is a frequent, often persistent complication in patients with major depressive disorder (MDD) and anorexia nervosa (AN) that increases the risk of pathologic fractures. The pathogenetic process underlying osteopenia in MDD and AN is still unclear, although several factors, including a dysbalance of cytokines, are associated with loss of bone mass. Alterations in the serum levels of cytokines have been observed in patients with MDD, AN, and other psychiatric disorders. Therefore, we examined serum levels of cytokines, markers of bone turnover, and BMD in 13 patients with MDD and a lifetime history of AN. Bone turnover markers (osteocalcin and C-terminal degradation products of type I collagen) and tumor necrosis factor alpha (TNF-alpha) in patients were significantly increased compared with those of the control group. Osteoprotegerin (OPG) in patients was significantly decreased. Eight of 13 patients (62%) displayed osteopenia at the lumbar spine. TNF-alpha correlated significantly with C-terminal degradation products of type I collagen, an osteoclastic marker, but significantly negatively with OPG. Our data suggest that TNF-alpha and OPG may play a role in the pathogenetic process underlying osteopenia in these patients.

Endoplasmic reticulum stress in diabetic mouse or glycated LDL-treated endothelial cells: protective effect of Saskatoon berry powder and cyanidin glycans.

PubMed

Zhao, Ruozhi; Xie, Xueping; Le, Khuong; Li, Wende; Moghadasian, Mohammed H; Beta, Trust; Shen, Garry X

2015-11-01

Endoplasmic reticulum (ER) stress is associated with insulin resistance and diabetic cardiovascular complications, and mechanism or remedy for ER stress remains to be determined. The results of the present study demonstrated that the levels of ER stress or unfolded protein response (UPR) markers, the intensity of thioflavin T (ThT) fluorescence and the abundances of GRP78/94, XBP-1 and CHOP proteins were elevated in cardiovascular tissue of diabetic leptin receptor-deficient (db/db) mice. Cyanidin-3-glucoside (C3G) and cyanidin-3-galactoside (C3Ga) are major anthocyanins in Saskatoon berry (SB) powder. The administration of 5% SB powder for 4 weeks attenuated ThT fluorescence and the UPR markers in hearts and aortae of wild-type and db/db mice. Treatment with glycated low-density lipoprotein (gLDL) increased ThT intensity in human umbilical vein endothelial cells (ECs). Elevated UPR markers were detected in gLDL-treated EC compared to control cultures. The involvement of ER stress in gLDL-treated EC was supported by that the addition of 4-phenyl butyrate acid (a known ER stress antagonist) inhibited gLDL-induced increases in ER stress or UPR markers. C3G at 30 μM or C3Ga at 100 μM reached their maximal inhibition on gLDL-induced increases in ThT, GRP78/94, XBP-1 and CHOP in EC. The results demonstrated that ER stress was enhanced in cardiovascular tissue of db/db mice or gLDL-treated EC. SB powder or cyanidin glycans prevented the abnormal increases in ER stress and UPR markers in cardiovascular tissue of diabetic db/db mice or gLDL-treated EC. Copyright © 2015 Elsevier Inc. All rights reserved.

Postpartum Circulating Markers of Inflammation and the Systemic Acute-Phase Response After Early-Onset Preeclampsia.

PubMed

van Rijn, Bas B; Bruinse, Hein W; Veerbeek, Jan H; Post Uiterweer, Emiel D; Koenen, Steven V; van der Bom, Johanna G; Rijkers, Ger T; Roest, Mark; Franx, Arie

2016-02-01

Preeclampsia is an inflammatory-mediated hypertensive disorder of pregnancy and seems to be an early indicator of increased cardiovascular risk, but mechanisms underlying this association are unclear. In this study, we identified levels of circulating inflammatory markers and dynamic changes in the systemic acute-phase response in 44 women with a history of severe early-onset preeclampsia, compared with 29 controls with only uneventful pregnancies at 1.5 to 3.5 years postpartum. Models used were in vivo seasonal influenza vaccination and in vitro whole-blood culture with T-cell stimulants and the toll-like receptor-4 ligand lipopolysaccharide. Outcome measures were C-reactive protein, interleukin-6 (IL-6), IL-18, fibrinogen, myeloperoxidase, and a panel of 13 cytokines representative of the innate and adaptive inflammatory response, in addition to established cardiovascular markers. The in vivo acute-phase response was higher for women with previous preeclampsia than that for controls without such a history, although only significant for C-reactive protein (P=0.04). Preeclampsia was associated with higher IL-1β (P<0.05) and IL-8 (P<0.01) responses to T-cell activation. Hierarchical clustering revealed 2 distinct inflammatory clusters associated with previous preeclampsia: an adaptive response cluster associated with increased C-reactive protein and IL-6 before and after vaccination, increased weight, and low high-density lipoprotein cholesterol; and a toll-like receptor-4 mediated the cluster associated with increased IL-18 before and after vaccination but not associated with other cardiovascular markers. Furthermore, we found interactions between previous preeclampsia, common TLR4 gene variants, and the IL-18 response to vaccination. In conclusion, preeclampsia is associated with alterations in the inflammatory response postpartum mostly independent of other established cardiovascular risk markers. © 2015 American Heart Association, Inc.

Four in vivo g-ratio-weighted imaging methods: Comparability and repeatability at the group level.

PubMed

Ellerbrock, Isabel; Mohammadi, Siawoosh

2018-01-01

A recent method, denoted in vivo g-ratio-weighted imaging, has related the microscopic g-ratio, only accessible by ex vivo histology, to noninvasive MRI markers for the fiber volume fraction (FVF) and myelin volume fraction (MVF). Different MRI markers have been proposed for g-ratio weighted imaging, leaving open the question which combination of imaging markers is optimal. To address this question, the repeatability and comparability of four g-ratio methods based on different combinations of, respectively, two imaging markers for FVF (tract-fiber density, TFD, and neurite orientation dispersion and density imaging, NODDI) and two imaging markers for MVF (magnetization transfer saturation rate, MT, and, from proton density maps, macromolecular tissue volume, MTV) were tested in a scan-rescan experiment in two groups. Moreover, it was tested how the repeatability and comparability were affected by two key processing steps, namely the masking of unreliable voxels (e.g., due to partial volume effects) at the group level and the calibration value used to link MRI markers to MVF (and FVF). Our data showed that repeatability and comparability depend largely on the marker for the FVF (NODDI outperformed TFD), and that they were improved by masking. Overall, the g-ratio method based on NODDI and MT showed the highest repeatability (90%) and lowest variability between groups (3.5%). Finally, our results indicate that the calibration procedure is crucial, for example, calibration to a lower g-ratio value (g = 0.6) than the commonly used one (g = 0.7) can change not only repeatability and comparability but also the reported dependency on the FVF imaging marker. Hum Brain Mapp 39:24-41, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Characterization and compilation of polymorphic simple sequence repeat (SSR) markers of peanut from public database

PubMed Central

2012-01-01

Background There are several reports describing thousands of SSR markers in the peanut (Arachis hypogaea L.) genome. There is a need to integrate various research reports of peanut DNA polymorphism into a single platform. Further, because of lack of uniformity in the labeling of these markers across the publications, there is some confusion on the identities of many markers. We describe below an effort to develop a central comprehensive database of polymorphic SSR markers in peanut. Findings We compiled 1,343 SSR markers as detecting polymorphism (14.5%) within a total of 9,274 markers. Amongst all polymorphic SSRs examined, we found that AG motif (36.5%) was the most abundant followed by AAG (12.1%), AAT (10.9%), and AT (10.3%).The mean length of SSR repeats in dinucleotide SSRs was significantly longer than that in trinucleotide SSRs. Dinucleotide SSRs showed higher polymorphism frequency for genomic SSRs when compared to trinucleotide SSRs, while for EST-SSRs, the frequency of polymorphic SSRs was higher in trinucleotide SSRs than in dinucleotide SSRs. The correlation of the length of SSR and the frequency of polymorphism revealed that the frequency of polymorphism was decreased as motif repeat number increased. Conclusions The assembled polymorphic SSRs would enhance the density of the existing genetic maps of peanut, which could also be a useful source of DNA markers suitable for high-throughput QTL mapping and marker-assisted selection in peanut improvement and thus would be of value to breeders. PMID:22818284

Construction of a High-Density American Cranberry (Vaccinium macrocarpon Ait.) Composite Map Using Genotyping-by-Sequencing for Multi-pedigree Linkage Mapping

PubMed Central

Schlautman, Brandon; Covarrubias-Pazaran, Giovanny; Diaz-Garcia, Luis; Iorizzo, Massimo; Polashock, James; Grygleski, Edward; Vorsa, Nicholi; Zalapa, Juan

2017-01-01

The American cranberry (Vaccinium macrocarpon Ait.) is a recently domesticated, economically important, fruit crop with limited molecular resources. New genetic resources could accelerate genetic gain in cranberry through characterization of its genomic structure and by enabling molecular-assisted breeding strategies. To increase the availability of cranberry genomic resources, genotyping-by-sequencing (GBS) was used to discover and genotype thousands of single nucleotide polymorphisms (SNPs) within three interrelated cranberry full-sib populations. Additional simple sequence repeat (SSR) loci were added to the SNP datasets and used to construct bin maps for the parents of the populations, which were then merged to create the first high-density cranberry composite map containing 6073 markers (5437 SNPs and 636 SSRs) on 12 linkage groups (LGs) spanning 1124 cM. Interestingly, higher rates of recombination were observed in maternal than paternal gametes. The large number of markers in common (mean of 57.3) and the high degree of observed collinearity (mean Pair-wise Spearman rank correlations >0.99) between the LGs of the parental maps demonstrates the utility of GBS in cranberry for identifying polymorphic SNP loci that are transferable between pedigrees and populations in future trait-association studies. Furthermore, the high-density of markers anchored within the component maps allowed identification of segregation distortion regions, placement of centromeres on each of the 12 LGs, and anchoring of genomic scaffolds. Collectively, the results represent an important contribution to the current understanding of cranberry genomic structure and to the availability of molecular tools for future genetic research and breeding efforts in cranberry. PMID:28250016

Whole genome sequences are required to fully resolve the linkage disequilibrium structure of human populations.

PubMed

Pengelly, Reuben J; Tapper, William; Gibson, Jane; Knut, Marcin; Tearle, Rick; Collins, Andrew; Ennis, Sarah

2015-09-03

An understanding of linkage disequilibrium (LD) structures in the human genome underpins much of medical genetics and provides a basis for disease gene mapping and investigating biological mechanisms such as recombination and selection. Whole genome sequencing (WGS) provides the opportunity to determine LD structures at maximal resolution. We compare LD maps constructed from WGS data with LD maps produced from the array-based HapMap dataset, for representative European and African populations. WGS provides up to 5.7-fold greater SNP density than array-based data and achieves much greater resolution of LD structure, allowing for identification of up to 2.8-fold more regions of intense recombination. The absence of ascertainment bias in variant genotyping improves the population representativeness of the WGS maps, and highlights the extent of uncaptured variation using array genotyping methodologies. The complete capture of LD patterns using WGS allows for higher genome-wide association study (GWAS) power compared to array-based GWAS, with WGS also allowing for the analysis of rare variation. The impact of marker ascertainment issues in arrays has been greatest for Sub-Saharan African populations where larger sample sizes and substantially higher marker densities are required to fully resolve the LD structure. WGS provides the best possible resource for LD mapping due to the maximal marker density and lack of ascertainment bias. WGS LD maps provide a rich resource for medical and population genetics studies. The increasing availability of WGS data for large populations will allow for improved research utilising LD, such as GWAS and recombination biology studies.

Treatment with eldecalcitol positively affects mineralization, microdamage, and collagen crosslinks in primate bone.

PubMed

Saito, Mitsuru; Grynpas, Marc D; Burr, David B; Allen, Matthew R; Smith, Susan Y; Doyle, Nancy; Amizuka, Norio; Hasegawa, Tomoka; Kida, Yoshikuni; Marumo, Keishi; Saito, Hitoshi

2015-04-01

Eldecalcitol (ELD), an active form of vitamin D analog approved for the treatment of osteoporosis in Japan, increases lumbar spine bone mineral density (BMD), suppresses bone turnover markers, and reduces fracture risk in patients with osteoporosis. We have previously reported that treatment with ELD for 6 months improved the mechanical properties of the lumbar spine in ovariectomized (OVX) cynomolgus monkeys. ELD treatment increased lumbar BMD, suppressed bone turnover markers, and reduced histomorphometric parameters of both bone formation and resorption in vertebral trabecular bone. In this study, we elucidated the effects of ELD on bone quality (namely, mineralization, microarchitecture, microdamage, and bone collagen crosslinks) in OVX cynomolgus monkeys in comparison with OVX-vehicle control monkeys. Density fractionation of bone powder prepared from lumbar vertebrae revealed that ELD treatment shifted the distribution profile of bone mineralization to a higher density, and backscattered electron microscopic imaging showed improved trabecular bone connectivity in the ELD-treated groups. Higher doses of ELD more significantly reduced the amount of microdamage compared to OVX-vehicle controls. The fractionated bone powder samples were divided according to their density, and analyzed for collagen crosslinks. Enzymatic crosslinks were higher in both the high-density (≥2.0 mg/mL) and low-density (<2.0 mg/mL) fractions from the ELD-treated groups than in the corresponding fractions in the OVX-vehicle control groups. On the other hand, non-enzymatic crosslinks were lower in both the high- and low-density fractions. These observations indicated that ELD treatment stimulated the enzymatic reaction of collagen crosslinks and bone mineralization, but prevented non-enzymatic reaction of collagen crosslinks and accumulation of bone microdamage. Bone anti-resorptive agents such as bisphosphonates slow down bone remodeling so that bone mineralization, bone microdamage, and non-enzymatic collagen crosslinks all increase. Bone anabolic agents such as parathyroid hormone decrease bone mineralization and bone microdamage by stimulating bone remodeling. ELD did not fit into either category. Histological analysis indicated that the ELD treatment strongly suppressed bone resorption by reducing the number of osteoclasts, while also stimulating focal bone formation without prior bone resorption (bone minimodeling). These bidirectional activities of ELD may account for its unique effects on bone quality. Copyright © 2014. Published by Elsevier Inc.

Cortex glial cells activation, associated with lowered mechanical thresholds and motor dysfunction, persists into adulthood after neonatal pain.

PubMed

Sanada, Luciana Sayuri; Sato, Karina Laurenti; Machado, Nathalia Leilane Berto; Carmo, Elisabete de Cássia do; Sluka, Kathleen A; Fazan, Valeria Paula Sassoli

2014-06-01

We investigated if changes in glial activity in cortical areas that process nociceptive stimuli persisted in adult rats after neonatal injury. Neonatal pain was induced by repetitive needle prickling on the right paw, twice per day for 15 days starting at birth. Wistar rats received either neonatal pain or tactile stimulation and were tested behaviorally for mechanical withdrawal thresholds of the paws and gait alterations, after 15 (P15) or 180 (P180) days of life. Brains from rats on P15 and P180 were immunostained for glial markers (GFAP, MCP-1, OX-42) and the following cortical areas were analyzed for immunoreactivity density: prefrontal, anterior insular, anterior cingulated, somatosensory and motor cortices. Withdrawal thresholds of the stimulated paw remained decreased on P180 after neonatal pain when compared to controls. Neonatal pain animals showed increased density for both GFAP and MCP-1 staining, but not for OX-42, in all investigated cortical areas on both experimental times (P15 and P180). Painful stimuli in the neonatal period produced pain behaviors immediately after injury that persisted in adult life, and was accompanied by increase in the glial markers density in cortical areas that process and interpret pain. Thus, long-lasting changes in cortical glial activity could be, at least in part, responsible for the persistent hyperalgesia in adult rats that suffered from neonatal pain. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

Increased serum cartilage oligomeric matrix protein levels and decreased patellar bone mineral density in patients with chondromalacia patellae

PubMed Central

Murphy, E; FitzGerald, O; Saxne, T; Bresnihan, B

2002-01-01

Background: Chondromalacia patellae is a potentially disabling disorder characterised by features of patellar cartilage degradation. Objective: To evaluate markers of cartilage and bone turnover in patients with chondromalacia patellae. Methods: 18 patients with chondromalacia patellae were studied. Serum cartilage oligomeric matrix protein (s-COMP) and bone sialoprotein (s-BSP) levels were measured by enzyme linked immunosorbent assay (ELISA) and compared with those of age and sex matched healthy control subjects. Periarticular bone mineral density (BMD) of both knee joints was assessed by dual energy x ray absorptiometry (DXA). Results: s-COMP levels were significantly raised in all patients with chondromalacia patellae compared with healthy control subjects (p=0.0001). s-BSP levels did not differ significantly between the groups (p=0.41). BMD of the patella was significantly reduced in patients with chondromalacia patellae compared with the control subjects (p=0.016). In patients with bilateral chondromalacia patellae, BMD of the patella was lower in the more symptomatic knee joint (p=0.005). Changes in periarticular BMD were localised to the patella and were not present in femoral regions. Neither s-COMP (p=0.18) nor s-BSP (p=0.40) levels correlated with patellar BMD. Conclusions: Increased s-COMP levels, reflecting cartilage degradation, and reduced BMD localised to the patella may represent clinically useful markers in the diagnosis and monitoring of patients with chondromalacia patellae. Measures of cartilage degradation did not correlate with loss of patellar bone density, suggesting dissociated pathophysiological mechanisms. PMID:12379520

Increased serum cartilage oligomeric matrix protein levels and decreased patellar bone mineral density in patients with chondromalacia patellae.

PubMed

Murphy, E; FitzGerald, O; Saxne, T; Bresnihan, B

2002-11-01

Chondromalacia patellae is a potentially disabling disorder characterised by features of patellar cartilage degradation. To evaluate markers of cartilage and bone turnover in patients with chondromalacia patellae. 18 patients with chondromalacia patellae were studied. Serum cartilage oligomeric matrix protein (s-COMP) and bone sialoprotein (s-BSP) levels were measured by enzyme linked immunosorbent assay (ELISA) and compared with those of age and sex matched healthy control subjects. Periarticular bone mineral density (BMD) of both knee joints was assessed by dual energy x ray absorptiometry (DXA). s-COMP levels were significantly raised in all patients with chondromalacia patellae compared with healthy control subjects (p=0.0001). s-BSP levels did not differ significantly between the groups (p=0.41). BMD of the patella was significantly reduced in patients with chondromalacia patellae compared with the control subjects (p=0.016). In patients with bilateral chondromalacia patellae, BMD of the patella was lower in the more symptomatic knee joint (p=0.005). Changes in periarticular BMD were localised to the patella and were not present in femoral regions. Neither s-COMP (p=0.18) nor s-BSP (p=0.40) levels correlated with patellar BMD. Increased s-COMP levels, reflecting cartilage degradation, and reduced BMD localised to the patella may represent clinically useful markers in the diagnosis and monitoring of patients with chondromalacia patellae. Measures of cartilage degradation did not correlate with loss of patellar bone density, suggesting dissociated pathophysiological mechanisms.

Alterations in Skeletal Muscle Indicators of Mitochondrial Structure and Biogenesis in Patients with Type 2 Diabetes and Heart Failure: Effects of Epicatechin Rich Cocoa

PubMed Central

Taub, Pam R.; Ramirez‐Sanchez, Israel; Ciaraldi, Theodore P.; Perkins, Guy; Murphy, Anne N.; Naviaux, Robert; Hogan, Michael; Maisel, Alan S.; Henry, Robert R.; Ceballos, Guillermo

2012-01-01

Abstract (‐)‐Epicatechin (Epi), a flavanol in cacao stimulates mitochondrial volume and cristae density and protein markers of skeletal muscle (SkM) mitochondrial biogenesis in mice. Type 2 diabetes mellitus (DM2) and heart failure (HF) are diseases associated with defects in SkM mitochondrial structure/function. A study was implemented to assess perturbations and to determine the effects of Epi‐rich cocoa in SkM mitochondrial structure and mediators of biogenesis. Five patients with DM2 and stage II/III HF consumed dark chocolate and a beverage containing approximately 100 mg of Epi per day for 3 months. We assessed changes in protein and/or activity levels of oxidative phosphorylation proteins, porin, mitofilin, nNOS, nitric oxide, cGMP, SIRT1, PGC1α, Tfam, and mitochondria volume and cristae abundance by electron microscopy from SkM. Apparent major losses in normal mitochondria structure were observed before treatment. Epi‐rich cocoa increased protein and/or activity of mediators of biogenesis and cristae abundance while not changing mitochondrial volume density. Epi‐rich cocoa treatment improves SkM mitochondrial structure and in an orchestrated manner, increases molecular markers of mitochondrial biogenesis resulting in enhanced cristae density. Future controlled studies are warranted using Epi‐rich cocoa (or pure Epi) to translate improved mitochondrial structure into enhanced cardiac and/or SkM muscle function. Clin Trans Sci 2012; Volume 5: 43–47 PMID:22376256

Melatonin improves bone mineral density at the femoral neck in postmenopausal women with osteopenia: a randomized controlled trial.

PubMed

Amstrup, Anne Kristine; Sikjaer, Tanja; Heickendorff, Lene; Mosekilde, Leif; Rejnmark, Lars

2015-09-01

Melatonin is known for its regulation of circadian rhythm. Recently, studies have shown that melatonin may have a positive effect on the skeleton. By increasing age, the melatonin levels decrease, which may lead to a further imbalanced bone remodeling. We aimed to investigate whether treatment with melatonin could improve bone mass and integrity in humans. In a double-blind RCT, we randomized 81 postmenopausal osteopenic women to 1-yr nightly treatment with melatonin 1 mg (N = 20), 3 mg (N = 20), or placebo (N = 41). At baseline and after 1-yr treatment, we measured bone mineral density (BMD) by dual X-ray absorptiometry, quantitative computed tomography (QCT), and high-resolution peripheral QCT (HR-pQCT) and determined calciotropic hormones and bone markers. Mean age of the study subjects was 63 (range 56-73) yr. Compared to placebo, femoral neck BMD increased by 1.4% in response to melatonin (P < 0.05) in a dose-dependent manner (P < 0.01), as BMD increased by 0.5% in the 1 mg/day group (P = 0.55) and by 2.3% (P < 0.01) in the 3 mg/day group. In the melatonin group, trabecular thickness in tibia increased by 2.2% (P = 0.04), and volumetric bone mineral density (vBMD) in the spine, by 3.6% (P = 0.04) in the 3 mg/day. Treatment did not significantly affect BMD at other sites or levels of bone turnover markers; however, 24-hr urinary calcium was decreased in response to melatonin by 12.2% (P = 0.02). In conclusion, 1-yr treatment with melatonin increased BMD at femoral neck in a dose-dependent manner, while high-dose melatonin increased vBMD in the spine. Further studies are needed to assess the mechanisms of action and whether the positive effect of nighttime melatonin will protect against fractures. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Lymphangiogenesis assessed using three methods is related to tumour grade, breast cancer subtype and expression of basal marker.

PubMed

Niemiec, Joanna; Adamczyk, Agnieszka; Ambicka, Aleksandra; Mucha-Małecka, Anna; Wysocki, Wojciech; Mituś, Jerzy; Ryś, Janusz

2012-11-01

Lymphangiogenesis is a potential indicator of cancer patients' survival. However, there is no standardisation of methodologies applied to the assessment of lymphatic vessel density. In 156 invasive ductal breast cancers (T  1/N+/M0), lymphatic and blood vessels were visualised using podoplanin and CD34, respectively. Based on these markers expression, four parameters were assessed: (i) distribution of podoplanin-stained vessels (DPV) - the percentage of fields with at least one lymphatic vessel (a simple method proposed by us), (ii) lymphatic vessel density (LVD), (iii) LVD to microvessel density ratio (LVD/MVD) and (iv) the expression of podoplanin in cancer-associated fibroblasts. Next, we estimated relations between the above-mentioned parameters and: (i) breast cancer subtype, (ii) tumour grade, and (iii) basal markers expression. We found that intensive lymphangiogenesis, assessed using all studied methods, is positively related to high tumour grade, triple negative or HER2 subtype and expression of basal markers. Whereas, the absence of podoplanin expression in fibroblasts of cancer stroma is related to luminal A subtype, low tumour grade or lack of basal markers expression. Distribution of podoplanin-stained vessels, assessed by a simple method proposed by us (indicating the percentage of fields with at least one lymphatic vessel), might be used instead of the "hot-spot" method.

Gene Methylation and Cytological Atypia in Random Fine-Needle Aspirates for Assessment of Breast Cancer Risk.

PubMed

Stearns, Vered; Fackler, Mary Jo; Hafeez, Sidra; Bujanda, Zoila Lopez; Chatterton, Robert T; Jacobs, Lisa K; Khouri, Nagi F; Ivancic, David; Kenney, Kara; Shehata, Christina; Jeter, Stacie C; Wolfman, Judith A; Zalles, Carola M; Huang, Peng; Khan, Seema A; Sukumar, Saraswati

2016-08-01

Methods to determine individualized breast cancer risk lack sufficient sensitivity to select women most likely to benefit from preventive strategies. Alterations in DNA methylation occur early in breast cancer. We hypothesized that cancer-specific methylation markers could enhance breast cancer risk assessment. We evaluated 380 women without a history of breast cancer. We determined their menopausal status or menstrual cycle phase, risk of developing breast cancer (Gail model), and breast density and obtained random fine-needle aspiration (rFNA) samples for assessment of cytopathology and cumulative methylation index (CMI). Eight methylated gene markers were identified through whole-genome methylation analysis and included novel and previously established breast cancer detection genes. We performed correlative and multivariate linear regression analyses to evaluate DNA methylation of a gene panel as a function of clinical factors associated with breast cancer risk. CMI and individual gene methylation were independent of age, menopausal status or menstrual phase, lifetime Gail risk score, and breast density. CMI and individual gene methylation for the eight genes increased significantly (P < 0.001) with increasing cytological atypia. The findings were verified with multivariate analyses correcting for age, log (Gail), log (percent density), rFNA cell number, and body mass index. Our results demonstrate a significant association between cytological atypia and high CMI, which does not vary with menstrual phase or menopause and is independent of Gail risk and mammographic density. Thus, CMI is an excellent candidate breast cancer risk biomarker, warranting larger prospective studies to establish its utility for cancer risk assessment. Cancer Prev Res; 9(8); 673-82. ©2016 AACR. ©2016 American Association for Cancer Research.

Comparison of breast density measurements made using ultrasound tomography and mammography

NASA Astrophysics Data System (ADS)

Sak, Mark; Duric, Neb; Littrup, Peter; Bey-Knight, Lisa; Krycia, Mark; Sherman, Mark E.; Boyd, Norman; Gierach, Gretchen L.

2015-03-01

Women with elevated mammographic percent density, defined as the ratio of fibroglandular tissue area to total breast area on a mammogram are at an increased risk of developing breast cancer. Ultrasound tomography (UST) is an imaging modality that can create tomographic sound speed images of a patient's breast, which can then be used to measure breast density. These sound speed images are useful because physical tissue density is directly proportional to sound speed. The work presented here updates previous results that compared mammographic breast density measurements with UST breast density measurements within an ongoing study. The current analysis has been expanded to include 158 women with negative digital mammographic screens who then underwent a breast UST scan. Breast density was measured for both imaging modalities and preliminary analysis demonstrated strong and positive correlations (Spearman correlation coefficient rs = 0.703). Additional mammographic and UST related imaging characteristics were also analyzed and used to compare the behavior of both imaging modalities. Results suggest that UST can be used among women with negative mammographic screens as a quantitative marker of breast density that may avert shortcomings of mammography.

Construction of a high-density genetic map using specific length amplified fragment markers and identification of a quantitative trait locus for anthracnose resistance in walnut (Juglans regia L.).

PubMed

Zhu, Yufeng; Yin, Yanfei; Yang, Keqiang; Li, Jihong; Sang, Yalin; Huang, Long; Fan, Shu

2015-08-18

Walnut (Juglans regia, 2n = 32, approximately 606 Mb per 1C genome) is an economically important tree crop. Resistance to anthracnose, caused by Colletotrichum gloeosporioides, is a major objective of walnut genetic improvement in China. The recently developed specific length amplified fragment sequencing (SLAF-seq) is an efficient strategy that can obtain large numbers of markers with sufficient sequence information to construct high-density genetic maps and permits detection of quantitative trait loci (QTLs) for molecular breeding. SLAF-seq generated 161.64 M paired-end reads. 153,820 SLAF markers were obtained, of which 49,174 were polymorphic. 13,635 polymorphic markers were sorted into five segregation types and 2,577 markers of them were used to construct genetic linkage maps: 2,395 of these fell into 16 linkage groups (LGs) for the female map, 448 markers for the male map, and 2,577 markers for the integrated map. Taking into account the size of all LGs, the marker coverage was 2,664.36 cM for the female map, 1,305.58 cM for the male map, and 2,457.82 cM for the integrated map. The average intervals between two adjacent mapped markers were 1.11 cM, 2.91 cM and 0.95 cM for three maps, respectively. 'SNP_only' markers accounted for 89.25% of the markers on the integrated map. Mapping markers contained 5,043 single nucleotide polymorphisms (SNPs) loci, which corresponded to two SNP loci per SLAF marker. According to the integrated map, we used interval mapping (Logarithm of odds, LOD > 3.0) to detect our quantitative trait. One QTL was detected for anthracnose resistance. The interval of this QTL ranged from 165.51 cM to 176.33 cM on LG14, and ten markers in this interval that were above the threshold value were considered to be linked markers to the anthracnose resistance trait. The phenotypic variance explained by each marker ranged from 16.2 to 19.9%, and their LOD scores varied from 3.22 to 4.04. High-density genetic maps for walnut containing 16 LGs were constructed using the SLAF-seq method with an F1 population. One QTL for walnut anthracnose resistance was identified based on the map. The results will aid molecular marker-assisted breeding and walnut resistance genes identification.

High-density genetic map construction and comparative genome analysis in asparagus bean.

PubMed

Huang, Haitao; Tan, Huaqiang; Xu, Dongmei; Tang, Yi; Niu, Yisong; Lai, Yunsong; Tie, Manman; Li, Huanxiu

2018-03-19

Genetic maps are a prerequisite for quantitative trait locus (QTL) analysis, marker-assisted selection (MAS), fine gene mapping, and assembly of genome sequences. So far, several asparagus bean linkage maps have been established using various kinds of molecular markers. However, these maps were all constructed by gel- or array-based markers. No maps based on sequencing method have been reported. In this study, an NGS-based strategy, SLAF-seq, was applied to create a high-density genetic map for asparagus bean. Through SLAF library construction and Illumina sequencing of two parents and 100 F2 individuals, a total of 55,437 polymorphic SLAF markers were developed and mined for SNP markers. The map consisted of 5,225 SNP markers in 11 LGs, spanning a total distance of 1,850.81 cM, with an average distance between markers of 0.35 cM. Comparative genome analysis with four other legume species, soybean, common bean, mung bean and adzuki bean showed that asparagus bean is genetically more related to adzuki bean. The results will provide a foundation for future genomic research, such as QTL fine mapping, comparative mapping in pulses, and offer support for assembling asparagus bean genome sequence.

Antihyperlipidemic Effect of Different Fractions Obtained from Teucrium polium Hydroalcoholic Extract in Rats.

PubMed

Safaeian, Leila; Ghanadian, Mustafa; Shafiee-Moghadam, Zahra

2018-01-01

This study was aimed to screen the antihyperlipidemic effect of different fractions of Teucrium polium to obtain the most efficient herbal fraction for isolation of bioactive constituents responsible for hypolipidemic activity. Chloroform, butanol, and aqueous fractions were obtained from hydroalcoholic extract of T. polium aerial parts using partitioning process. To induce hyperlipidemia, dexamethasone (Dex) was injected 10 mg/kg/day (s.c.) for 8 days. In the test groups, animals received 50, 100 and 150 mg/kg of T. polium hydroalcoholic extract and different fractions orally simultaneously with Dex. Serum lipid profile and hepatic marker enzymes were evaluated using biochemical kits. All treatments, especially chloroform and aqueous fractions, reversed serum lipid markers in hyperlipidemic rats. Maximum reduction in triglyceride (60.2%, P < 0.001) and maximum elevation in high-density lipoprotein (HDL) (35.0%, P < 0.01) was observed for chloroform fraction. Maximum cholesterol-lowering effect (29.0%, P < 0.001) and maximum reduction in low-density lipoprotein were found for hydroalcoholic extract (72.9%, P < 0.001). Aqueous fraction improved all lipid markers at the highest dose. Butanol fraction decreased triglyceride at the lowest dose (43.9%, P < 0.001) and increased HDL (33%, P < 0.05) at the highest dose. There was a significant increase in alanine aminotransferase and aspartate aminotransferase levels in all tested groups compared to normal group ( P < 0.001). This study showed strong antihyperlipidemic effect of various fractions derived from hydroalcoholic extract of T. polium . Chloroform and aqueous fractions may be worthy candidates for isolation of bioactive hypolipidemic constituents. However, possible hepatotoxicity should be considered for clinical application.

Markers of apoptosis induction and proliferation in the orbitofrontal cortex in alcohol dependence

PubMed Central

Whittom, Angela; Villarreal, Ashley; Soni, Madhav; Owusu-Duku, Beverly; Meshram, Ashish; Rajkowska, Grazyna; Stockmeier, Craig A.; Miguel-Hidalgo, Jose J.

2014-01-01

Background Alcohol-dependent (ALC) subjects exhibit glial and neuronal pathology in the prefrontal cortex (PFC). However, in many patients, neurophysiological disturbances are not associated with catastrophic cell depletion despite prolonged alcohol abuse. It is still unclear how some relevant markers of a cell’s propensity to degenerate or proliferate are changed in the PFC of ALC subjects without major neurological disorders. Methods Levels of pro-apoptotic caspase 8 (C8), X-linked inhibitor of apoptosis protein (XIAP), direct IAP binding protein with low pI (DIABLO), proliferating cell nuclear antigen (PCNA), and density of cells immunoreactive (-IR) for proliferation marker Ki-67 were measured postmortem in the left orbitofrontal cortex (OFC) of 29 subjects with alcohol dependence and 23 non-psychiatric comparison subjects. Results ALC subjects had significantly higher levels of the 14kDa C8 fragment (C8-14), an indicator of C8 activation. However, there was no change in the levels of DIABLO, XIAP or in the DIABLO/XIAP ratio. PCNA protein level and density of Ki-67-IR cells were not significantly changed in alcoholics, although PCNA levels were increased in older ALC subjects as compared to controls. Conclusions Significant increase of a C8 activation indicator was found in alcoholism, but without significant changes in XIAP level, DIABLO/XIAP ratio, or Ki-67 labeling. These results would help to explain the absence of catastrophic cell loss in the PFC of many alcohol dependent subjects, while still being consistent with an alcoholism-related vulnerability to slow decline in glial cells and neurons in the OFC of alcoholics. PMID:25421516

Adiponectin and markers of metabolic syndrome in obese children and adolescents: impact of 8-mo regular physical exercise program.

PubMed

Nascimento, Henrique; Costa, Elísio; Rocha, Susana; Lucena, Clarice; Rocha-Pereira, Petronila; Rêgo, Carla; Mansilha, Helena Ferreira; Quintanilha, Alexandre; Aires, Luísa; Mota, Jorge; Santos-Silva, Alice; Belo, Luís

2014-08-01

Adiponectin circulates as low-, medium-, and high-molecular-weight multimers (LMW, MMW, and HMW) and influences lipid profile and insulin resistance (IR), HMW being considered as the most biologically active form. We aimed to study the relation between adiponectin and markers of metabolic syndrome (MS) in pediatric obesity, and the impact of physical exercise. The study consisted of a cross-sectional part and an 8-mo physical exercise program. Lipid profile, insulin, glucose, C-reactive protein (CRP), total adiponectin (TA), and homeostasis model assessment IR (HOMA-IR) were measured. Adiponectin multimers were studied in a prepubertal group. Obesity is associated with increased dyslipidemia, IR, and inflammation. TA is correlated inversely with adiposity, triglycerides, HOMA-IR, and CRP, and positively with high-density lipoprotein cholesterol (HDLc)/total cholesterol (TC) ratio. HMW mimicked TA associations. The intervention program led to a reduction of TC, low-density lipoprotein cholesterol (LDLc), insulin, HOMA-IR, and trunk percentage of fat, and an increase of HDLc/TC ratio, in the obese group. BMI improvements prevented adiponectin reduction and correlated with increments in HMW and MMW. Obesity-related increase in MS features might be linked to lower adiponectin. HMW and MMW were the multimers that most explained the MS features. The intervention program improved the lipid profile and IR, and prevented the reduction of adiponectin.

Voluntary resistance wheel exercise from mid-life prevents sarcopenia and increases markers of mitochondrial function and autophagy in muscles of old male and female C57BL/6J mice.

PubMed

White, Zoe; Terrill, Jessica; White, Robert B; McMahon, Christopher; Sheard, Phillip; Grounds, Miranda D; Shavlakadze, Tea

2016-12-13

There is much interest in the capacity of resistance exercise to prevent the age-related loss of skeletal muscle mass and function, known as sarcopenia. This study investigates the molecular basis underlying the benefits of resistance exercise in aging C57BL/6J mice of both sexes. This study is the first to demonstrate that long-term (34 weeks) voluntary resistance wheel exercise (RWE) initiated at middle age, from 15 months, prevents sarcopenia in selected hindlimb muscles and causes hypertrophy in soleus, by 23 months of age in both male and female C57BL/6J mice. Compared with 23-month-old sedentary (SED) controls, RWE (0-6 g of resistance) increased intramuscular mitochondrial density and oxidative capacity (measured by citrate synthase and NADH-TR) and increased LC3II/I ratios (a marker of autophagy) in exercised mice of both sexes. RWE also reduced mRNA expression of Gadd45α (males only) and Runx1 (females only) but had no effect on other markers of denervation including Chrng, Chrnd, Musk, and Myog. RWE increased heart mass in all mice, with a more pronounced increase in females. Significant sex differences were also noted among SED mice, with Murf1 mRNA levels increasing in male, but decreasing in old female mice between 15 and 23 months. Overall, long-term RWE initiated from 15 month of age significantly improved some markers of the mitochondrial and autophagosomal pathways and prevented age-related muscle wasting.

Endometrial vessel maturation in women exposed to levonorgestrel-releasing intrauterine system for a short or prolonged period of time.

PubMed

Stéphanie, Ravet; Labied, Soraya; Blacher, Silvia; Frankenne, Francis; Munaut, Carine; Fridman, Viviana; Beliard, Aude; Foidart, Jean-Michel; Nisolle, Michelle

2007-12-01

Levonorgestrel-releasing intrauterine system (LNG-IUS), although inserted to reduce heavy menstruation, causes irregular early transient bleeding. The objective of the study was to document quantitative changes in endometrial vessels of short- (< or =3 months) and long-term (> or =12 months) LNG users. The area, density and maturation of endometrial vessels were quantified in 19 endometrial biopsies of women with LNG-IUS and in 10 normally ovulating patients during mid-luteal phase. Vessel maturation was evaluated by double immunostaining using anti-von Willebrand factor (endothelial cell marker) and anti-alpha Smooth Muscle Actin (vascular smooth muscle cells) antibodies. Vessel area, number and density were quantified with a novel computer-assisted image analysis system. Endometrium exposed to LNG-IUS for 1-3 months displayed a 11.5-fold increase in small naked vessel number. The partially mature vessel (alphaSMA partially positive) number increased six times. After long-term LNG-IUS treatment, the immature and partially mature vessel number remained four times higher than in the control group. Vessel area and density also increased dramatically in a time-dependent pattern with LNG-IUS use. Levonorgestrel affects blood vessel number, area, density and maturation in a time-dependent pattern that may explain the early transient increase in breakthrough bleeding with the LNG-IUS.

Increased Intake of Selected Vegetables, Herbs and Fruit may Reduce Bone Turnover in Post-Menopausal Women

PubMed Central

Gunn, Caroline Ann; Weber, Janet Louise; McGill, Anne-Thea; Kruger, Marlena Cathorina

2015-01-01

Increased consumption of vegetables/herbs/fruit may reduce bone turnover and urinary calcium loss in post-menopausal women because of increased intake of polyphenols and potassium, but comparative human studies are lacking. The main aim was to compare bone turnover markers and urinary calcium excretion in two randomised groups (n = 50) of healthy post-menopausal women consuming ≥9 servings of different vegetables/herbs/fruit combinations (three months). Group A emphasised a generic range of vegetables/herbs/fruit, whereas Group B emphasised specific vegetables/herbs/fruit with bone resorption-inhibiting properties (Scarborough Fair Diet), with both diets controlled for potential renal acid load (PRAL). Group C consumed their usual diet. Plasma bone markers, urinary electrolytes (24 h) and estimated dietary PRAL were assessed at baseline and 12 weeks. Procollagen type I N propeptide (PINP) decreased (−3.2 μg/L, p < 0.01) in the B group only, as did C-terminal telopeptide of type I collagen (CTX) (−0.065 μg/L, p < 0.01) in women with osteopenia compared to those with normal bone mineral density (BMD) within this group. Intervention Groups A and B had decreased PRAL, increased urine pH and significantly decreased urinary calcium loss. Urinary potassium increased in all groups, reflecting a dietary change. In conclusion, Group B demonstrated positive changes in both turnover markers and calcium conservation. PMID:25856221

The quantitative evaluation of cholinergic markers in spatial memory improvement induced by nicotine-bucladesine combination in rats.

PubMed

Azami, Kian; Etminani, Maryam; Tabrizian, Kaveh; Salar, Fatemeh; Belaran, Maryam; Hosseini, Asieh; Hosseini-Sharifabad, Ali; Sharifzadeh, Mohammad

2010-06-25

We previously showed that post-training intra-hippocampal infusion of nicotine-bucladesine combination enhanced spatial memory retention in the Morris water maze. Here we investigated the role of cholinergic markers in nicotine-bucladesine combination-induced memory improvement. We assessed the expression of choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) in CA1 region of the hippocampus and medial septal area (MSA) of the brain. Post-training bilateral infusion of a low concentration of either nicotine or bucladesine into the CA1 region of the hippocampus did not affect spatial memory significantly. Quantitative immunostaining analysis of optical density in CA1 regions and evaluation of immunopositive neurons in medial septal area of brain sections from all combination groups revealed a significant increase (P<0.001) in the ChAT and VAChT immunoreactivity. The maximum increase was observed with combination of 10-microM/side bucladesine and 0.5 microg/side nicotine and in a concentration dependent manner. Also, increase in the optical density and amount of ChAT and VAChT immunostaining correlated with the decrease in escape latency and traveled distance in rats treated with nicotine and low dose of bucladesine. Taken together, these results suggest that significant increases of ChAT and VAChT protein expressions in the CA1 region and medial septal area are the possible mechanisms of spatial memory improvement induced by nicotine-bucladesine combination. (c) 2010 Elsevier B.V. All rights reserved.

Reduced Neurite Density in Neuronal Cell Cultures Exposed to Serum of Patients with Bipolar Disorder

PubMed Central

Wollenhaupt-Aguiar, Bianca; Pfaffenseller, Bianca; Chagas, Vinicius de Saraiva; Castro, Mauro A A; Passos, Ives Cavalcante; Kauer-Sant’Anna, Márcia; Kapczinski, Flavio

2016-01-01

Background: Increased inflammatory markers and oxidative stress have been reported in serum among patients with bipolar disorder (BD). The aim of this study is to assess whether biochemical changes in the serum of patients induces neurotoxicity in neuronal cell cultures. Methods: We challenged the retinoic acid-differentiated human neuroblastoma SH-SY5Y cells with the serum of BD patients at early and late stages of illness and assessed neurite density and cell viability as neurotoxic endpoints. Results: Decreased neurite density was found in neurons treated with the serum of patients, mostly patients at late stages of illness. Also, neurons challenged with the serum of late-stage patients showed a significant decrease in cell viability. Conclusions: Our findings showed that the serum of patients with bipolar disorder induced a decrease in neurite density and cell viability in neuronal cultures. PMID:27207915

Development of an experimental diet model in rats to study hyperlipidemia and insulin resistance, markers for coronary heart disease

PubMed Central

Munshi, Renuka P.; Joshi, Samidha G.; Rane, Bhagyeshri N.

2014-01-01

Objectives: The objective of this study is to develop an experimental model of hyperlipidemia and insulin resistance (IR), markers of coronary heart disease (CHD) using high fat and high sugar (HFHS) diet and to evaluate the efficacy of the model using atorvastatin, a known antihyperlipidemic drug, pioglitazone, a known insulin sensitizer, and Tinospora cordifolia (Tc), an antidiabetic plant. Materials and Methods: Following Institutional Animal Ethics Committee permission, the study was conducted in male Wistar rats (200-270 g). The model was developed using a high fat (vanaspati ghee: coconut oil, 3:1) oral diet along with 25% fructose (high sugar) added in drinking water over a period of 6 weeks. Atorvastatin (2.1 mg/kg/day), pioglitazone (2.7 mg/kg/day) and Tc (200 mg/kg/day) were administered 3 weeks after initiation of HFHS diet and continued for another 3 weeks. Parameters assessed were weight, lipid profile, fasting blood glucose, insulin, and gastric emptying. Serum malondialdehyde (MDA) and catalase were assessed as markers of oxidative stress. Results: Administration of HFHS diet demonstrated a significant increase in blood glucose, insulin, total and low density lipoprotein cholesterol and triglycerides with a decrease in high density lipoprotein cholesterol. Treatment with test drugs decreased blood sugar, insulin, lipid parameters, increased gastric emptying rate, decreased MDA levels, and catalase activity when compared to HFHS diet group, confirming the efficacy of the model. Atherogenic index of all the test drugs (0.48, 0.57, and 0.53) was significantly lower as compared to HFHS diet group (1.107). Conclusion: This study confirms the development of a diet based cost-effective and time efficient experimental model, which can be used to study two important markers of cardiovascular disease that is, hyperlipidemia and IR and to explore the efficacy of new molecules in CHD. PMID:24987172

Accelerating public sector rice breeding with high-density KASP markers derived from whole genome sequencing of indica rice.

PubMed

Steele, Katherine A; Quinton-Tulloch, Mark J; Amgai, Resham B; Dhakal, Rajeev; Khatiwada, Shambhu P; Vyas, Darshna; Heine, Martin; Witcombe, John R

2018-01-01

Few public sector rice breeders have the capacity to use NGS-derived markers in their breeding programmes despite rapidly expanding repositories of rice genome sequence data. They rely on > 18,000 mapped microsatellites (SSRs) for marker-assisted selection (MAS) using gel analysis. Lack of knowledge about target SNP and InDel variant loci has hampered the uptake by many breeders of Kompetitive allele-specific PCR (KASP), a proprietary technology of LGC genomics that can distinguish alleles at variant loci. KASP is a cost-effective single-step genotyping technology, cheaper than SSRs and more flexible than genotyping by sequencing (GBS) or array-based genotyping when used in selection programmes. Before this study, there were 2015 rice KASP marker loci in the public domain, mainly identified by array-based screening, leaving large proportions of the rice genome with no KASP coverage. Here we have addressed the urgent need for a wide choice of appropriate rice KASP assays and demonstrated that NGS can detect many more KASP to give full genome coverage. Through re-sequencing of nine indica rice breeding lines or released varieties, this study has identified 2.5 million variant sites. Stringent filtering of variants generated 1.3 million potential KASP assay designs, including 92,500 potential functional markers. This strategy delivers a 650-fold increase in potential selectable KASP markers at a density of 3.1 per 1 kb in the indica crosses analysed and 377,178 polymorphic KASP design sites on average per cross. This knowledge is available to breeders and has been utilised to improve the efficiency of public sector breeding in Nepal, enabling identification of polymorphic KASP at any region or quantitative trait loci in relevant crosses. Validation of 39 new KASP was carried out by genotyping progeny from a range of crosses to show that they detected segregating alleles. The new KASP have replaced SSRs to aid trait selection during marker-assisted backcrossing in these crosses, where target traits include rice blast and BLB resistance loci. Furthermore, we provide the software for plant breeders to generate KASP designs from their own datasets.

In peripubertal girls, artistic gymnastics improves areal bone mineral density and femoral bone geometry without affecting serum OPG/RANKL levels.

PubMed

Maïmoun, L; Coste, O; Mariano-Goulart, D; Galtier, F; Mura, T; Philibert, P; Briot, K; Paris, F; Sultan, C

2011-12-01

Peripubertal artistic gymnasts display elevated areal bone mineral density at various bone sites, despite delayed menarche and a high frequency of menstrual disorders, factors that may compromise bone health. The concomitant improvement in femoral bone geometry and strength suggested that this type of physical activity might have favourable clinical impact. The purpose of this study is to evaluate the effect of artistic gymnastics (GYM) on areal bone mineral density (aBMD), femoral bone geometry and bone markers and its relationship with the osteoprotegerin (OPG)/rank-ligand (RANKL) system in peripubertal girls. Forty-six girls (age 10-17.2 years) were recruited for this study: 23 elite athletes in the GYM group (training 12-30 h/week, age at start of training 5.3 years) and 23 age-matched (± 6 months; leisure physical activity ≤ 3 h/week) controls (CON). The aBMD at whole body, total proximal femur, lumbar spine, mid-radius and skull was determined using dual-X-ray absorptiometry. Hip structural analysis (HSA software) was applied at the femur to evaluate cross-sectional area (CSA, cm(2)), cross-sectional moment of inertia (CSMI, cm(4)), and the section modulus (Z, cm(3)) and buckling ratio at neck, intertrochanteric region and shaft. Markers of bone turnover and OPG/RANKL levels were also analysed. GYM had higher (5.5-16.4%) non-adjusted aBMD and adjusted aBMD for age, fat-free soft tissue and fat mass at all bone sites, skull excepted and the difference increased with age. In the three femoral regions adjusted for body weight and height, CSA (12.5-18%), CSMI (14-18%), Z (15.5-18.6%) and mean cortical thickness (13.6-21%) were higher in GYM than CON, while the buckling ratio (21-27.1%) was lower. Bone markers decreased with age in both groups and GYM presented higher values than CON only in the postmenarchal period. A similar increase in RANKL with age without OPG variation was observed for both groups. GYM is associated not only with an increase in aBMD but also an improvement in bone geometry associated with an increase in bone remodelling. These adaptations seem to be independent of the OPG/RANKL system.

Variation of genetic diversity in a rapidly expanding population of the greater long-tailed hamster (Tscherskia triton) as revealed by microsatellites.

PubMed

Xu, Laixiang; Xue, Huiliang; Song, Mingjing; Zhao, Qinghua; Dong, Jingping; Liu, Juan; Guo, Yu; Xu, Tongqin; Cao, Xiaoping; Wang, Fusheng; Wang, Shuqing; Hao, Shushen; Yang, Hefang; Zhang, Zhibin

2013-01-01

Genetic diversity is essential for persistence of animal populations over both the short- and long-term. Previous studies suggest that genetic diversity may decrease with population decline due to genetic drift or inbreeding of small populations. For oscillating populations, there are some studies on the relationship between population density and genetic diversity, but these studies were based on short-term observation or in low-density phases. Evidence from rapidly expanding populations is lacking. In this study, genetic diversity of a rapidly expanding population of the Greater long-tailed hamsters during 1984-1990, in the Raoyang County of the North China Plain was studied using DNA microsatellite markers. Results show that genetic diversity was positively correlated with population density (as measured by % trap success), and the increase in population density was correlated with a decrease of genetic differentiation between the sub-population A and B. The genetic diversity tended to be higher in spring than in autumn. Variation in population density and genetic diversity are consistent between sub-population A and B. Such results suggest that dispersal is density- and season-dependent in a rapidly expanding population of the Greater long-tailed hamster. For typically solitary species, increasing population density can increase intra-specific attack, which is a driving force for dispersal. This situation is counterbalanced by decreasing population density caused by genetic drift or inbreeding as the result of small population size. Season is a major factor influencing population density and genetic diversity. Meanwhile, roads, used to be considered as geographical isolation, have less effect on genetic differentiation in a rapidly expanding population. Evidences suggest that gene flow (Nm) is positively correlated with population density, and it is significant higher in spring than that in autumn.

IAP-Based Cell Sorting Results in Homogeneous Transplantable Dopaminergic Precursor Cells Derived from Human Pluripotent Stem Cells.

PubMed

Lehnen, Daniela; Barral, Serena; Cardoso, Tiago; Grealish, Shane; Heuer, Andreas; Smiyakin, Andrej; Kirkeby, Agnete; Kollet, Jutta; Cremer, Harold; Parmar, Malin; Bosio, Andreas; Knöbel, Sebastian

2017-10-10

Human pluripotent stem cell (hPSC)-derived mesencephalic dopaminergic (mesDA) neurons can relieve motor deficits in animal models of Parkinson's disease (PD). Clinical translation of differentiation protocols requires standardization of production procedures, and surface-marker-based cell sorting is considered instrumental for reproducible generation of defined cell products. Here, we demonstrate that integrin-associated protein (IAP) is a cell surface marker suitable for enrichment of hPSC-derived mesDA progenitor cells. Immunomagnetically sorted IAP + mesDA progenitors showed increased expression of ventral midbrain floor plate markers, lacked expression of pluripotency markers, and differentiated into mature dopaminergic (DA) neurons in vitro. Intrastriatal transplantation of IAP + cells sorted at day 16 of differentiation in a rat model of PD resulted in functional recovery. Grafts from sorted IAP + mesDA progenitors were more homogeneous in size and DA neuron density. Thus, we suggest IAP-based sorting for reproducible prospective enrichment of mesDA progenitor cells in clinical cell replacement strategies. Copyright © 2017 Miltenyi Biotec GmbH. Published by Elsevier Inc. All rights reserved.

Comparative prognostic relevance of breast intra-tumoral microvessel density evaluated by CD105 and CD146: A pilot study of 42 cases.

PubMed

Martinez, Leandro Marcelo; Labovsky, Vivian; Calcagno, María de Luján; Davies, Kevin Mauro; Rivello, Hernán Garcia; Wernicke, Alejandra; Calvo, Juan Carlos; Chasseing, Norma Alejandra

2016-04-01

Angiogenesis is a key process for metastatic progression. While it has been established that the evaluation of breast tumoral microvessel density by CD105 marker is a potential prognostic parameter, its evaluation by CD146 marker has been poorly studied. The purpose of this study was to compare the prognostic value of intra-tumoral microvessel density assayed by CD105 and CD146 in early breast cancer patients. 42 women with breast infiltrative ductal carcinoma (I and II-stages) were retrospectively reviewed. Intra-tumoral microvessel density was immunohistochemically examined using antibodies anti-CD105 and CD146 in paraffin-embedded tissues, and their association with classical prognostic-markers, metastatic recurrence, metastasis-free survival and overall survival was analyzed. High microvessel density assessed by CD146 was significantly associated with a higher risk of developing metastasis (p=0.0310) and a shorter metastasis-free survival (p=0.0197). In contrast, when we used the CD105-antibody, we did not find any significant association. Finally, CD146 showed to be an independent predictive indicator for metastasis-free survival (p=0.0055). Our data suggest that the intra-tumoral microvessel density evaluated by CD146 may be a more suitable predictor of metastatic development than that evaluated by CD105 in early breast cancer. Copyright © 2016 Elsevier GmbH. All rights reserved.

A novel approach to rapidly prevent age-related cognitive decline

PubMed Central

Adlard, Paul A; Sedjahtera, Amelia; Gunawan, Lydia; Bray, Lisa; Hare, Dominic; Lear, Jessica; Doble, Philip; Bush, Ashley I; Finkelstein, David I; Cherny, Robert A

2014-01-01

The loss of cognitive function is a pervasive and often debilitating feature of the aging process for which there are no effective therapeutics. We hypothesized that a novel metal chaperone (PBT2; Prana Biotechnology, Parkville, Victoria, Australia) would enhance cognition in aged rodents. We show here that PBT2 rapidly improves the performance of aged C57Bl/6 mice in the Morris water maze, concomitant with increases in dendritic spine density, hippocampal neuron number and markers of neurogenesis. There were also increased levels of specific glutamate receptors (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-d-aspartate), the glutamate transporter (VGLUT1) and glutamate itself. Markers of synaptic plasticity [calmodulin-dependent protein kinase II (CaMKII) and phosphorylated CaMKII, CREB, synaptophysin] were also increased following PBT2 treatment. We also demonstrate that PBT2 treatment results in a subregion-specific increase in hippocampal zinc, which is increasingly recognized as a potent neuromodulator. These data demonstrate that metal chaperones are a novel approach to the treatment of age-related cognitive decline. PMID:24305557

Changes in glomerular parietal epithelial cells in mouse kidneys with advanced age

PubMed Central

Roeder, Sebastian S.; Stefanska, Ania; Eng, Diana G.; Kaverina, Natalya; Sunseri, Maria W.; McNicholas, Bairbre A.; Rabinovitch, Peter; Engel, Felix B.; Daniel, Christoph; Amann, Kerstin; Lichtnekert, Julia; Pippin, Jeffrey W.

2015-01-01

Kidney aging is accompanied by characteristic changes in the glomerulus, but little is known about the effect of aging on glomerular parietal epithelial cells (PECs), nor if the characteristic glomerular changes in humans and rats also occur in very old mice. Accordingly, a descriptive analysis was undertaken in 27-mo-old C57B6 mice, considered advanced age. PEC density was significantly lower in older mice compared with young mice (aged 3 mo), and the decrease was more pronounced in juxtamedullary glomeruli compared with outer cortical glomeruli. In addition to segmental and global glomerulosclerosis in older mice, staining for matrix proteins collagen type IV and heparan sulfate proteoglycan were markedly increased in Bowman's capsules of older mouse glomeruli, consistent with increased extracellular matrix production by PECs. De novo staining for CD44, a marker of activated and profibrotic PECs, was significantly increased in aged glomeruli. CD44 staining was more pronounced in the juxtamedullary region and colocalized with phosphorylated ERK. Additionally, a subset of aged PECs de novo expressed the epithelial-to-mesenchymal transition markers α-smooth muscle and vimentin, with no changes in epithelial-to-mesenchymal transition markers E-cadherin and β-catenin. The mural cell markers neural/glial antigen 2, PDGF receptor-β, and CD146 as well as Notch 3 were also substantially increased in aged PECs. These data show that mice can be used to better understand the aging kidney and that PECs undergo substantial changes, especially in juxtamedullary glomeruli, that may participate in the overall decline in glomerular structure and function with advancing age. PMID:26017974

ASYMMETRIC DIMETHYLARGININE LEVELS AND ATHEROSCLEROSIS MARKERS IN CUSHING SYNDROME.

PubMed

Ozsurekci, Cemile Gulbas; Akturk, Mujde; Ozkan, Cigdem; Gulbahar, Ozlem; Altinova, Alev Eroglu; Yalcin, Muhittin; Arslan, Emre; Toruner, Fusun

2016-09-01

As a consequence of hypercortisolism, Cushing syndrome (CS) is frequently observed with other diseases that are associated with atherosclerosis, including diabetes mellitus, dyslipidemia, hypertension, and obesity. Cardiovascular disease (CVD) is the primary cause of mortality and morbidity in CS. We investigate CVD risk markers such as asymmetric dimethylarginine (ADMA), lipoprotein-associated phospholipase A2 (Lp-PLA2), highsensitive C-reactive protein (hsCRP), homocysteine, lipid levels, ankle-brachial index (ABI), and carotid intimamedia thickness (CIMT) in CS. Our study included 27 patients with CS and 27 age-, sex-, body mass index (BMI)-, and comorbid disease-matched control subjects. Plasma ADMA levels were significantly lower in the CS group than the control group (P = .013). Total cholesterol, low-density lipoprotein, triglycerides, high-density lipoprotein, and apolipoprotein A1 and apolipoprotein B levels were higher in patients with CS than the control group (P<.05). We did not find any statistically significant differences in levels of hsCRP, Lp-PLA2, or homocysteine or CIMT and ABI measurements between the CS group and comorbidity-matched control group (P>.05). We found that ADMA levels were lower in CS, the finding that should be further investigated. Levels of hsCRP, Lp-PLA2, and homocysteine levels and CIMT and ABI measurements were similar between the CS group and comorbidity-matched control group. None of these markers was prominent to show an increased risk of CVD in CS, independent of the comorbidities of CS. ABI = ankle-brachial index Apo = apolipoprotein ADMA = asymmetric dimethylarginine BMI = body mass index CVD = cardiovascular disease CIMT = carotid intima-media thickness CS = Cushing syndrome DM = diabetes mellitus DDAH = dimethylarginine dimethylaminohydrolase ELISA = enzyme-linked immunosorbent assay HDL = high-density lipoprotein hsCRP = high-sensitive C-reactive protein HOMA-IR = homeostatic model assessment of insulin resistance HT = hypertension LDL = low-density lipoprotein Lp-PLA2 = lipoprotein-associated phospholipase A2 Lp-a = lipoprotein a NO = nitric oxide.

Cardiovascular risk in systemic lupus erythematosus--evidence of increased oxidative stress and dyslipidaemia.

PubMed

Nuttall, S L; Heaton, S; Piper, M K; Martin, U; Gordon, C

2003-06-01

Systemic lupus erythematosus (SLE) is associated with severe and premature cardiovascular disease, which is not explained by traditional risk factors alone. This study aimed to investigate markers of oxidative stress, lipid metabolism and inflammation as potential cardiovascular risk factors in women with SLE. Venous blood samples were taken from 53 female Caucasian patients with SLE and from healthy age- and sex-matched controls. Samples were analysed for markers of oxidative stress, lipid metabolism [including low-density lipoprotein (LDL) subfraction profile] and C-reactive protein (CRP). Female SLE patients had an atherogenic lipid profile characterized by raised total cholesterol and triglycerides, and the presence of small, dense LDL subfractions compared with healthy controls. These changes were associated with increased oxidative damage and a moderately raised CRP. The results provide evidence for free radical and inflammatory activity in SLE and suggest potential targets to reduce the risk of cardiovascular disease in these patients.

SNOM and AFM microscopy techniques to study the effect of non-ionizing radiation on the morphological and biochemical properties of human keratinocytes cell line (HaCaT).

PubMed

Rieti, S; Manni, V; Lisi, A; Giuliani, L; Sacco, D; D'Emilia, E; Cricenti, A; Generosi, R; Luce, M; Grimaldi, S

2004-01-01

In this study we have employed atomic force microscopy (AFM) and scanning near-field optical microscopy (SNOM) techniques to study the effect of the interaction between human keratinocytes (HaCaT) and electromagnetic fields at low frequency. HaCaT cells were exposed to a sinusoidal magnetic field at a density of 50 Hz, 1 mT. AFM analysis revealed modification in shape and morphology in exposed cells with an increase in the areas of adhesion between cells. This latter finding was confirmed by SNOM indirect immunofluorescence analysis performed with a fluorescent antibody against the adhesion marker beta4 integrin, which revealed an increase of beta4 integrin segregation in the cell membrane of 50-Hz exposed cells, suggesting that a higher percentage of these cells shows a modified pattern of this adhesion marker.

Construction of a high-density genetic map by specific locus amplified fragment sequencing (SLAF-seq) and its application to Quantitative Trait Loci (QTL) analysis for boll weight in upland cotton (Gossypium hirsutum.).

PubMed

Zhang, Zhen; Shang, Haihong; Shi, Yuzhen; Huang, Long; Li, Junwen; Ge, Qun; Gong, Juwu; Liu, Aiying; Chen, Tingting; Wang, Dan; Wang, Yanling; Palanga, Koffi Kibalou; Muhammad, Jamshed; Li, Weijie; Lu, Quanwei; Deng, Xiaoying; Tan, Yunna; Song, Weiwu; Cai, Juan; Li, Pengtao; Rashid, Harun or; Gong, Wankui; Yuan, Youlu

2016-04-11

Upland Cotton (Gossypium hirsutum) is one of the most important worldwide crops it provides natural high-quality fiber for the industrial production and everyday use. Next-generation sequencing is a powerful method to identify single nucleotide polymorphism markers on a large scale for the construction of a high-density genetic map for quantitative trait loci mapping. In this research, a recombinant inbred lines population developed from two upland cotton cultivars 0-153 and sGK9708 was used to construct a high-density genetic map through the specific locus amplified fragment sequencing method. The high-density genetic map harbored 5521 single nucleotide polymorphism markers which covered a total distance of 3259.37 cM with an average marker interval of 0.78 cM without gaps larger than 10 cM. In total 18 quantitative trait loci of boll weight were identified as stable quantitative trait loci and were detected in at least three out of 11 environments and explained 4.15-16.70 % of the observed phenotypic variation. In total, 344 candidate genes were identified within the confidence intervals of these stable quantitative trait loci based on the cotton genome sequence. These genes were categorized based on their function through gene ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis and eukaryotic orthologous groups analysis. This research reported the first high-density genetic map for Upland Cotton (Gossypium hirsutum) with a recombinant inbred line population using single nucleotide polymorphism markers developed by specific locus amplified fragment sequencing. We also identified quantitative trait loci of boll weight across 11 environments and identified candidate genes within the quantitative trait loci confidence intervals. The results of this research would provide useful information for the next-step work including fine mapping, gene functional analysis, pyramiding breeding of functional genes as well as marker-assisted selection.

Noninvasive markers of bone metabolism in the rhesus monkey: normal effects of age and gender

NASA Technical Reports Server (NTRS)

Cahoon, S.; Boden, S. D.; Gould, K. G.; Vailas, A. C.

1996-01-01

Measurement of bone turnover in conditions such as osteoporosis has been limited by the need for invasive iliac bone biopsy to reliably determine parameters of bone metabolism. Recent advances in the area of serum and urinary markers of bone metabolism have raised the possibility for noninvasive measurements; however, little nonhuman primate data exist for these parameters. The purpose of this experiment was to define the normal range and variability of several of the newer noninvasive bone markers which are currently under investigation in humans. The primary intent was to determine age and gender variability, as well as provide some normative data for future experiments in nonhuman primates. Twenty-four rhesus macaques were divided into equal groups of male and female according to the following age groupings: 3 years, 5-10 years, 15-20 years, and > 25 years. Urine was collected three times daily for a four-day period and measured for several markers of bone turnoverm including pyridinoline (PYD), deoxypyrodinoline (DPD), hydroxyproline, and creatinine. Bone mineral density measurements of the lumbar spine were performed at the beginning and end of the study period. Serum was also obtained at the time of bone densitometry for measurement of osteocalcin levels by radioimmunoassay. There were no significant differences in bone mineral density, urine PYD, or urine DPD based on gender. Bone density was lowest in the youngest animals, peaked in the 15-20-year group, but again decreased in the oldest animals. The osteocalcin, PYD, and DPD levels followed an inversely related pattern to bone density. The most important result was the relative age insensitivity of the ratio of PYD:DPD in monkeys up to age 20 years. Since bone density changes take months or years to become measurable and iliac biopsies are invasive, the PYD/DPD marker ratio may have important implications for rapid noninvasive measurement of the effects of potential treatments for osteoporosis in the non-human primate model.

Bone Turnover Markers and Lean Mass in Pubescent Boys: Comparison Between Elite Soccer Players and Controls.

PubMed

Nebigh, Ammar; Abed, Mohamed Elfethi; Borji, Rihab; Sahli, Sonia; Sellami, Slaheddine; Tabka, Zouhair; Rebai, Haithem

2017-11-01

The aim of this study was to examine the relationship between bone mass and bone turnover markers with lean mass (LM) in pubescent soccer players. Two groups participated in this study, which included 65 elite young soccer players who trained for 6-8 hours per week and 60 controls. Bone mineral density; bone mineral content in the whole body, lower limbs, lumbar spine, and femoral neck; biochemical markers of osteocalcin; bone-specific alkaline phosphatase; C-telopeptide type I collagen; and total LM were assessed. Young soccer players showed higher bone mineral density and bone mineral content in the whole body and weight-bearing sites (P < .001). Indeed, the total LM correlated with whole-body bone mineral density and bone mineral content (P < .001). There were significant differences within the bone formation markers and osteocalcin (formation)/C-telopeptide type I collagen (resorption) ratio between young soccer players compared with the control group, but no significant difference in C-telopeptide type I collagen was observed between the 2 groups. This study showed a significant positive correlation among bone-specific alkaline phosphatase, osteocalcin, and total LM (r = .29; r = .31; P < .05) only for the young soccer players. Findings of this study highlight the importance of soccer practice for bone mineral parameters and bone turnover markers during the puberty stage.

Construction of an SNP-based high-density linkage map for flax (Linum usitatissimum L.) using specific length amplified fragment sequencing (SLAF-seq) technology.

PubMed

Yi, Liuxi; Gao, Fengyun; Siqin, Bateer; Zhou, Yu; Li, Qiang; Zhao, Xiaoqing; Jia, Xiaoyun; Zhang, Hui

2017-01-01

Flax is an important crop for oil and fiber, however, no high-density genetic maps have been reported for this species. Specific length amplified fragment sequencing (SLAF-seq) is a high-resolution strategy for large scale de novo discovery and genotyping of single nucleotide polymorphisms. In this study, SLAF-seq was employed to develop SNP markers in an F2 population to construct a high-density genetic map for flax. In total, 196.29 million paired-end reads were obtained. The average sequencing depth was 25.08 in male parent, 32.17 in the female parent, and 9.64 in each F2 progeny. In total, 389,288 polymorphic SLAFs were detected, from which 260,380 polymorphic SNPs were developed. After filtering, 4,638 SNPs were found suitable for genetic map construction. The final genetic map included 4,145 SNP markers on 15 linkage groups and was 2,632.94 cM in length, with an average distance of 0.64 cM between adjacent markers. To our knowledge, this map is the densest SNP-based genetic map for flax. The SNP markers and genetic map reported in here will serve as a foundation for the fine mapping of quantitative trait loci (QTLs), map-based gene cloning and marker assisted selection (MAS) for flax.

Antiosteoporotic Effect of Combined Extract of Morus alba and Polygonum odoratum

PubMed Central

Sungkamanee, Sudarat; Thukham-mee, Wipawee

2014-01-01

Due to the limitation of osteoporosis therapy, the alternative therapies from natural sources have been considered. In this study, we aimed to determine the antiosteoporotic effect of the combined extract of Morus alba and Polygonum odoratum leaves. Ovariectomized rats, weighing 200–220 g, were orally given the combined extract at doses of 5, 150, and 300 mg·kg−1 BW for 3 months. At the end of study, blood was collected to determine serum osteocalcin, calcium, and alkaline phosphatase level. In addition, tibia bone was isolated to determine bone oxidative stress markers, cortical bone thickness, and density of osteoblast. The combined extract decreased oxidative stress and osteoclast density but increased osteoblast density and cortical thickness. The elevation of serum calcium, alkaline phosphatase, and osteocalcin was also observed. These results suggested the antiosteoporotic effect of the combined extract via the increased growth formation together with the suppression of bone resorption. However, further studies concerning chronic toxicity and the underlying mechanism are required. PMID:25478061

Interaction between PON1 and population density in amyotrophic lateral sclerosis.

PubMed

Diekstra, Frank P; Beleza-Meireles, Ana; Leigh, Nigel P; Shaw, Christopher E; Al-Chalabi, Ammar

2009-01-28

Paraoxonase polymorphisms have been associated with amyotrophic lateral sclerosis (ALS). Paraoxonases are detoxifying enzymes involved in the metabolism of organophosphates. We tested the hypothesis that genetic variation within paraoxonase genes would interact with the environmental exposure to paraoxonase substrates. We used population density in the location of residence of ALS patients as a surrogate marker for environmental exposure. Paraoxonase genotypes at previously associated single nucleotide polymorphisms rs662, rs854560, rs6954345, and rs11981433 were studied in 98 patients from the South East England ALS population-based register. A case-only analysis was carried out and median population density was used to categorize patients into rural or urban environments. We found a significant interaction with population density for marker rs854560 (L55M) in ALS.

Cholesterol oversynthesis markers define familial combined hyperlipidemia versus other genetic hypercholesterolemias independently of body weight.

PubMed

Baila-Rueda, Lucía; Cenarro, Ana; Lamiquiz-Moneo, Itziar; Perez-Calahorra, Sofía; Bea, Ana M; Marco-Benedí, Victoria; Jarauta, Estíbaliz; Mateo-Gallego, Rocío; Civeira, Fernando

2018-03-01

Primary hypercholesterolemia of genetic origin, negative for mutations in LDLR, APOB, PCSK9 and APOE genes (non-FH GH), and familial combined hyperlipidemia (FCHL) are polygenic genetic diseases that occur with hypercholesterolemia, and both share a very high cardiovascular risk. In order to better characterize the metabolic abnormalities associated with these primary hypercholesterolemias, we used noncholesterol sterols, as markers of cholesterol metabolism, to determine their potential differences. Hepatic cholesterol synthesis markers (desmosterol and lanosterol) and intestinal cholesterol absorption markers (sitosterol and campesterol) were determined in non-FH GH (n=200), FCHL (n=100) and genetically defined heterozygous familial hypercholesterolemia subjects (FH) (n=100) and in normolipidemic controls (n=100). FCHL subjects had lower cholesterol absorption and higher cholesterol synthesis than non-FH GH, FH and controls (P<.001). When noncholesterol sterols were adjusted by body mass index (BMI), FCHL subjects had higher cholesterol synthesis than non-FG GH, FH and controls (P<.001). An increase in BMI was accompanied by increased cholesterol synthesis and decreased cholesterol absorption in non-FH GH, FH and controls. However, this association between BMI and cholesterol synthesis was not observed in FCHL. Non-high-density-lipoprotein cholesterol showed a positive correlation with cholesterol synthesis markers similar to that of BMI in non-FH GH, FH and normolipemic controls, but there was no correlation in FCHL. These results suggest that FCHL and non-FH GH have different mechanisms of production. Cholesterol synthesis and absorption are dependent of BMI in non-FH GH, but cholesterol synthesis is increased as a pathogenic mechanism in FCHL independently of age, gender, APOE and BMI. Copyright © 2017 Elsevier Inc. All rights reserved.

NGEE Arctic Plant Traits: Shrub Transects, Kougarok Road Mile Marker 64, Seward Peninsula, Alaska, 2016

DOE Data Explorer

Verity Salmon; Colleen Iversen; Peter Thornton; Ma

2017-03-01

Transect data is from point center quarter surveys for shrub density performed in July 2016 at the Kougarok hill slope located at Kougarok Road, Mile Marker 64. For each sample point along the transects, moving averages for shrub density and shrub basal area are provided along with GPS coordinates, average shrub height and active layer depth. The individual height, basal area, and species of surveyed shrubs are also included. Data upload will be completed January 2017.

Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study.

PubMed

Naylor, K E; Jacques, R M; Paggiosi, M; Gossiel, F; Peel, N F A; McCloskey, E V; Walsh, J S; Eastell, R

2016-01-01

We used bone turnover markers to identify women who responded to bisphosphonate treatment for osteoporosis. Response was more likely with alendronate and ibandronate than risedronate. There was a greater decrease in bone markers if baseline bone turnover markers were higher and if the patient took more than 80 % of her medication. Biochemical response to bisphosphonate therapy can be assessed using either a decrease in bone turnover marker beyond the least significant change (LSC) or a reduction to within a reference interval (RI). We compared the performance of these target responses and determined whether response was related to the type of bisphosphonate, compliance and baseline bone turnover markers. Biochemical responses to three oral bisphosphonates were assessed in an open, controlled trial comprising 172 postmenopausal osteoporotic women (age 53-84 years), randomised to alendronate, ibandronate or risedronate, plus calcium and vitamin D supplementation for 2 years. The LSC for each marker was derived within the study population, whereas RIs were obtained from a control group of healthy premenopausal women (age 35-40 years). Over 70 % of women achieved a target response for serum CTX and PINP, irrespective of the approach used. The percentage decrease at 12 weeks was greater for women with baseline PINP above the RI -63 % (difference 13 %, 95 % CI 0 to 27.1, P = 0.049) and good compliance -67 % (difference 15.9 %, 95 % CI 6.3 to 25.5, P = 0.001). Responders had a greater increase in spine bone density compared to nonresponders; for example 6.2 vs. 2.3 % (difference 3.9 %, 95 % CI 1.6 to 6.3, P = 0.0011) for PINP LSC. The magnitude of change in bone markers was greater with ibandronate and alendronate than risedronate. Both approaches to response identified similar proportions of women as responders. Nonresponders had smaller increases in BMD, and we suggest that biochemical assessment of response is a useful tool for the management of women with postmenopausal osteoporosis.

Structural properties of oligonucleotide monolayers on gold surfaces probed by fluorescence investigations.

PubMed

Rant, Ulrich; Arinaga, Kenji; Fujita, Shozo; Yokoyama, Naoki; Abstreiter, Gerhard; Tornow, Marc

2004-11-09

We present optical investigations on the conformation of oligonucleotide layers on Au surfaces. Our studies concentrate on the effect of varying surface coverage densities on the structural properties of layers of 12- and 24mer single-stranded DNA, tethered to the Au surface at one end while being labeled with a fluorescent marker at the opposing end. The distance-dependent energy transfer from the marker dye to the metal surface, which causes quenching of the observed fluorescence, is used to provide information on the orientation of the DNA strands relative to the surface. Variations in the oligonucleotide coverage density, as determined from electrochemical quantification, over 2 orders of magnitude are achieved by employing different preparation conditions. The observed enhancement in fluorescence intensity with increasing DNA coverage can be related to a model involving mutual steric interactions of oligonucleotides on the surface, as well as fluorescence quenching theory. Finally, the applicability of the presented concepts for investigations of heterogeneous monolayers is demonstrated by means of studying the coadsorption of mercaptohexanol onto DNA-modified Au surfaces.

Assessment of bone metabolism in premenopausal females with hyperthyroidism and hypothyroidism.

PubMed

Tuchendler, Dominika; Bolanowski, Marek

2013-01-01

Osteoporosis is one of the commonest metabolic diseases of bone. Its possible causes may include thyroid hormonal dysfunction. The objective of this study was to evaluate the effects of hyperthyroidism and hypothyroidism on osseous tissue metabolism in premenopausal women. 38 women with hyperthyroidism, 40 with hypothyroidism and 41 healthy women participated in this study. Initially after 6 and 12 months, each patient underwent selected hormonal, immunological and biochemical tests, measurement of concentrations of bone turnover markers and densitometry were also performed. On initial evaluation, lower cortical bone density was found in patients with hyperthyroidism (femoral neck). After 12 months, an increase in BMD was seen, but it was still lower than in the control group. Statistically significantly higher concentrations of bone turnover markers, decreasing from the sixth month of treatment, were noted only in the group with hyperthyroidism. Statistically significant differences were not noted in the femoral neck nor in the lumbar spine BMD in patients with hypothyroidism. Hyperthyroidism poses a negative effect on bone metabolism. Hypothyroidism in premenopausal females does not have any influence on bone density.

Association between the triglyceride to high-density lipoprotein cholesterol ratio and insulin resistance in Korean adolescents: a nationwide population-based study.

PubMed

Park, Jae-Min; Lee, Jee-Yon; Dong, Jae June; Lee, Duk-Chul; Lee, Yong-Jae

2016-11-01

Studies have suggested the triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) as a surrogate marker of insulin resistance. However, few studies have examined the association between TG/HDL-C and insulin resistance in the general adolescent population. This study aimed to examine the association between TG/HDL-C and insulin resistance in a nationally representative sample of Korean adolescents. A total of 2649 participants aged 12-18 years were selected from the 2007 to 2010 Korean National Health and Nutrition Examination Survey (KNHANES). Insulin resistance was defined as the homeostatic model assessment of insulin resistance (HOMA-IR) values greater than the 80th percentile. The mean values of most cardiometabolic variables increased proportionally with TG/HDL-C quartiles. Compared to individuals in the lowest TG/HDL-C quartile, the odds ratio for insulin resistance for individuals in the highest quartile was 2.91 in boys and 2.38 in girls after adjusting for confounding variables. This study suggests that TG/HDL-C could be a convenient marker for identifying Korean adolescents with insulin resistance.

Effect of alcohol consumption on biological markers associated with risk of coronary heart disease: systematic review and meta-analysis of interventional studies

PubMed Central

Brien, Susan E; Ronksley, Paul E; Turner, Barbara J; Mukamal, Kenneth J

2011-01-01

Objective To systematically review interventional studies of the effects of alcohol consumption on 21 biological markers associated with risk of coronary heart disease in adults without known cardiovascular disease. Design Systematic review and meta-analysis. Data sources Medline (1950 to October 2009) and Embase (1980 to October 2009) without limits. Study selection Two reviewers independently selected studies that examined adults without known cardiovascular disease and that compared fasting levels of specific biological markers associated with coronary heart disease after alcohol use with those after a period of no alcohol use (controls). 4690 articles were screened for eligibility, the full texts of 124 studies reviewed, and 63 relevant articles selected. Results Of 63 eligible studies, 44 on 13 biomarkers were meta-analysed in fixed or random effects models. Quality was assessed by sensitivity analysis of studies grouped by design. Analyses were stratified by type of beverage (wine, beer, spirits). Alcohol significantly increased levels of high density lipoprotein cholesterol (pooled mean difference 0.094 mmol/L, 95% confidence interval 0.064 to 0.123), apolipoprotein A1 (0.101 g/L, 0.073 to 0.129), and adiponectin (0.56 mg/L, 0.39 to 0.72). Alcohol showed a dose-response relation with high density lipoprotein cholesterol (test for trend P=0.013). Alcohol decreased fibrinogen levels (−0.20 g/L, −0.29 to −0.11) but did not affect triglyceride levels. Results were similar for crossover and before and after studies, and across beverage types. Conclusions Favourable changes in several cardiovascular biomarkers (higher levels of high density lipoprotein cholesterol and adiponectin and lower levels of fibrinogen) provide indirect pathophysiological support for a protective effect of moderate alcohol use on coronary heart disease. PMID:21343206

Construction of a High-Density American Cranberry (Vaccinium macrocarpon Ait.) Composite Map Using Genotyping-by-Sequencing for Multi-pedigree Linkage Mapping.

PubMed

Schlautman, Brandon; Covarrubias-Pazaran, Giovanny; Diaz-Garcia, Luis; Iorizzo, Massimo; Polashock, James; Grygleski, Edward; Vorsa, Nicholi; Zalapa, Juan

2017-04-03

The American cranberry ( Vaccinium macrocarpon Ait.) is a recently domesticated, economically important, fruit crop with limited molecular resources. New genetic resources could accelerate genetic gain in cranberry through characterization of its genomic structure and by enabling molecular-assisted breeding strategies. To increase the availability of cranberry genomic resources, genotyping-by-sequencing (GBS) was used to discover and genotype thousands of single nucleotide polymorphisms (SNPs) within three interrelated cranberry full-sib populations. Additional simple sequence repeat (SSR) loci were added to the SNP datasets and used to construct bin maps for the parents of the populations, which were then merged to create the first high-density cranberry composite map containing 6073 markers (5437 SNPs and 636 SSRs) on 12 linkage groups (LGs) spanning 1124 cM. Interestingly, higher rates of recombination were observed in maternal than paternal gametes. The large number of markers in common (mean of 57.3) and the high degree of observed collinearity (mean Pair-wise Spearman rank correlations >0.99) between the LGs of the parental maps demonstrates the utility of GBS in cranberry for identifying polymorphic SNP loci that are transferable between pedigrees and populations in future trait-association studies. Furthermore, the high-density of markers anchored within the component maps allowed identification of segregation distortion regions, placement of centromeres on each of the 12 LGs, and anchoring of genomic scaffolds. Collectively, the results represent an important contribution to the current understanding of cranberry genomic structure and to the availability of molecular tools for future genetic research and breeding efforts in cranberry. Copyright © 2017 Schlautman et al.

A high-resolution whole genome radiation hybrid map of human chromosome 17q22-q25.3 across the genes for GH and TK

DOE Office of Scientific and Technical Information (OSTI.GOV)

Foster, J.W.; Schafer, A.J.; Critcher, R.

1996-04-15

We have constructed a whole genome radiation hybrid (WG-RH) map across a region of human chromosome 17q, from growth hormone (GH) to thymidine kinase (TK). A panel of 128 WG-RH hybrid cell lines generated by X-irradiation and fusion has been tested for the retention of 39 sequence-tagged site (STS) markers by the polymerase chain reaction. This genome mapping technique has allowed the integration of existing VNTR and microsatellite markers with additional new markers and existing STS markers previously mapped to this region by other means. The WG-RH map includes eight expressed sequence tag (EST) and three anonymous markers developed formore » this study, together with 23 anonymous microsatellites and five existing ESTs. Analysis of these data resulted in a high-density comprehensive map across this region of the genome. A subset of these markers has been used to produce a framework map consisting of 20 loci ordered with odds greater than 1000:1. The markers are of sufficient density to build a YAC contig across this region based on marker content. We have developed sequence tags for both ends of a 2.1-Mb YAC and mapped these using the WG-RH panel, allowing a direct comparison of cRay{sub 6000} to physical distance. 31 refs., 3 figs., 2 tabs.« less

Effect of rhythmic gymnastics on volumetric bone mineral density and bone geometry in premenarcheal female athletes and controls.

PubMed

Tournis, S; Michopoulou, E; Fatouros, I G; Paspati, I; Michalopoulou, M; Raptou, P; Leontsini, D; Avloniti, A; Krekoukia, M; Zouvelou, V; Galanos, A; Aggelousis, N; Kambas, A; Douroudos, I; Lyritis, G P; Taxildaris, K; Pappaioannou, N

2010-06-01

Weight-bearing exercise during growth exerts positive effects on the skeleton. Our objective was to test the hypothesis that long-term elite rhythmic gymnastics exerts positive effects on volumetric bone mineral density and geometry and to determine whether exercise-induced bone adaptation is associated with increased periosteal bone formation or medullary contraction using tibial peripheral quantitative computed tomography and bone turnover markers. We conducted a cross-sectional study at a tertiary center. We studied 26 elite premenarcheal female rhythmic gymnasts (RG) and 23 female controls, aged 9-13 yr. We measured bone age, volumetric bone mineral density, bone mineral content (BMC), cortical thickness, cortical and trabecular area, and polar stress strength index (SSIp) by peripheral quantitative computed tomography of the left tibia proximal to the distal metaphysis (trabecular) at 14, 38 (cortical), and 66% (muscle mass) from the distal end and bone turnover markers. The two groups were comparable according to height and chronological and bone age. After weight adjustment, cortical BMC, area, and thickness at 38% were significantly higher in RG (P < 0.005-0.001). Periosteal circumference, SSIp, and muscle area were higher in RG (P < 0.01-0.001). Muscle area was significantly associated with cortical BMC, area, and SSIp, whereas years of training showed positive association with cortical BMC, area, and thickness independent of chronological age. RG in premenarcheal girls may induce positive adaptations on the skeleton, especially in cortical bone. Increased duration of exercise is associated with a positive response of bone geometry.

Inflammatory bowel disease causes reversible suppression of osteoblast and chondrocyte function in mice.

PubMed

Harris, Laura; Senagore, Patricia; Young, Vincent B; McCabe, Laura R

2009-05-01

Decreased bone density and stature can occur in pediatric patients with inflammatory bowel disease (IBD). Little is known about how IBD broadly impacts the skeleton. To evaluate the influence of an acute episode of IBD on growing bone, 4-wk-old mice were administered 5% dextran sodium sulfate (DSS) for 5 days to induce colitis and their recovery was monitored. During active disease and early recovery, trabecular bone mineral density, bone volume, and thickness were decreased. Cortical bone thickness, outer perimeter, and density were also decreased, whereas inner perimeter and marrow area were increased. These changes appear to maintain bone strength since measures of moments of inertia were similar between DSS-treated and control mice. Histological (static and dynamic), serum, and RNA analyses indicate that a decrease in osteoblast maturation and function account for changes in bone density. Unlike some conditions of bone loss, marrow adiposity did not increase. Similar to reports in humans, bone length decreased and correlated with decreases in growth plate thickness and chondrocyte marker expression. During disease recovery, mice experienced a growth spurt that led to their achieving final body weights and bone length, density, and gene expression similar to healthy controls. Increased TNF-alpha and decreased IGF-I serum levels were observed with active disease and returned to normal with recovery. Changes in serum TNF-alpha (increased) and IGF-I (decreased) paralleled changes in bone parameters and returned to normal values with recovery, suggesting a potential role in the skeletal response.

MCP-1-Induced Protein Promotes Endothelial-Like and Angiogenic Properties in Human Bone Marrow Monocytic Cells

PubMed Central

Wang, Kangkai; Zhelyabovska, Olga; Saad, Yasser; Kolattukudy, Pappachan E.

2013-01-01

Monocytic cells enhance neovascularization by releasing proangiogenic mediators and/or by transdifferentiating into endothelial-like cells. However, the mechanisms that govern this transdifferentiation process are largely unknown. Recently, monocyte chemotactic protein-1 (MCP-1)-induced protein (MCPIP) has been identified as a novel CCCH-type zinc-finger protein expressed primarily in monocytic cells. Here, we analyzed whether MCPIP might exert angiogenic effects by promoting differentiation of monocytic cells into endothelial cell (EC)-like phenotype. The expression of MCPIP increased during MCP-1-induced transdifferentiation in human bone marrow mononuclear cells (BMNCs). Knockdown of MCPIP with small interfering RNA (siRNA) abolished MCP-1-induced expression of EC markers Flk-1 and Tie-2 in human BMNCs. BMNCs transfected with MCPIP expression vector displayed EC-like morphology accompanied by downregulation of monocytic markers CD14 and CD11b, upregulation of EC markers Flk-1 and Tie-2, induction of cadherin (cdh)-12 and -19, activation of endoplasmic reticulum (ER) stress, and autophagy. Knockdown of cdh-12 or cdh-19 markedly inhibited MCPIP-induced enhancement of cell attachment and EC-marker expression. Inhibition of ER stress by tauroursodeoxycholate abolished MCPIP-induced expression of EC markers. Inhibition of autophagy by knockdown of Beclin-1 with siRNA or by an autophagy inhibitor 3′-methyladenine inhibited MCPIP-induced expression of EC markers. Expression of MCPIP in BMNCs enhanced uptake of acetylated low-density lipoprotein (acLDL), formation of EC-colony, incorporation of cells into capillary-like structure on Matrigel, and exhibited increased neovascularization in the ischemic hindlimb in mice. These results demonstrate that MCPIP may be an important regulator of inflammatory angiogenesis and provide novel mechanistic insights into the link between MCP-1 and cardiovascular diseases. PMID:24008336

Mapping of AFLP markers linked to seed coat colour loci in Brassica juncea (L.) Czern.

PubMed

Sabharwal, V; Negi, M S; Banga, S S; Lakshmikumaran, M

2004-06-01

Association mapping of the seed-coat colour with amplified fragment length polymorphism (AFLP) markers was carried out in 39 Brassica juncea lines. The lines had genetically diverse parentages and varied for seed-coat colour and other morphological characters. Eleven AFLP primer combinations were used to screen the 39 B. juncea lines, and a total of 335 polymorphic bands were detected. The bands were analysed for association with seed-coat colour using multiple regression analysis. This analysis revealed 15 markers associated with seed-coat colour, obtained with eight AFLP primer combinations. The marker E-ACA/M-CTG(350 )explained 69% of the variation in seed-coat colour. This marker along with markers E-AAC/M-CTC(235 )and E-AAC/M-CTA(250) explained 89% of the total variation. The 15 associated markers were validated for linkage with the seed-coat colour loci using a recombinant inbred line (RIL) mapping population. Bands were amplified with the eight AFLP primer combinations in 54 RIL progenies. Of the 15 associated markers, 11 mapped on two linkage groups. Eight markers were placed on linkage group 1 at a marker density of 6.0 cM, while the remaining three were mapped on linkage group 2 at a marker density of 3.6 cM. Marker E-ACA/M-CTG(350 )co-segregated with Gene1 controlling seed-coat colour; it was specific for yellow seed-coat colour and mapped to linkage group 1. Marker E-AAC/M-CTC(235) (AFLP8), which had been studied previously, was present on linkage group 2; it was specific for brown seed-coat colour. Since AFLP markers are not adapted for large-scale applications in plant breeding, it is important to convert these to sequence-characterised amplified region (SCAR) markers. Marker E-AAC/M-CTC(235) (AFLP8) had been previously converted into a SCAR. Work is in progress to convert the second of the linked markers, E-ACA/M-CTG(350), to a SCAR. The two linked AFLP markers converted to SCARs will be useful for developing yellow-seeded B. juncea lines by means of marker-assisted selection.

A high-density genetic map and growth related QTL mapping in bighead carp (Hypophthalmichthys nobilis)

PubMed Central

Fu, Beide; Liu, Haiyang; Yu, Xiaomu; Tong, Jingou

2016-01-01

Growth related traits in fish are controlled by quantitative trait loci (QTL), but no QTL for growth have been detected in bighead carp (Hypophthalmichthys nobilis) due to the lack of high-density genetic map. In this study, an ultra-high density genetic map was constructed with 3,121 SNP markers by sequencing 117 individuals in a F1 family using 2b-RAD technology. The total length of the map was 2341.27 cM, with an average marker interval of 0.75 cM. A high level of genomic synteny between our map and zebrafish was detected. Based on this genetic map, one genome-wide significant and 37 suggestive QTL for five growth-related traits were identified in 6 linkage groups (i.e. LG3, LG11, LG15, LG18, LG19, LG22). The phenotypic variance explained (PVE) by these QTL varied from 15.4% to 38.2%. Marker within the significant QTL region was surrounded by CRP1 and CRP2, which played an important role in muscle cell division. These high-density map and QTL information provided a solid base for QTL fine mapping and comparative genomics in bighead carp. PMID:27345016

Eldecalcitol normalizes bone turnover markers regardless of their pre-treatment levels.

PubMed

Shiraki, Masataka; Saito, Hitoshi; Matsumoto, Toshio

2012-09-01

Three-year treatment with eldecalcitol has been shown to improve lumbar and total hip bone mineral density (BMD), decrease bone turnover markers, and lower the incidences of vertebral and wrist fractures in patients with osteoporosis more than with treatment with alfacalcidol under vitamin D repletion. The purpose of this study was to determine whether there was a risk of eldecalcitol causing severely suppressed bone turnover in osteoporosis patients with low pre-treatment levels of bone turnover markers. Post-hoc analysis was conducted on the data from a 3-year, randomized, double-blind, active-comparator, clinical trial of eldecalcitol versus alfacalcidol under vitamin D repletion conducted in Japan. Enrolled patients with baseline measurements of bone turnover markers were stratified into tertiles according to their pre-treatment levels of serum bone-specific alkaline phosphatase, serum procollagen type I N-terminal propeptide, or urinary collagen-N-telopeptide. Eldecalcitol treatment rapidly reduced bone turnover markers, and kept them within the normal range. However, in the patients whose baseline values for bone turnover were low, eldecalcitol treatment did not further reduce bone turnover markers during the 3-year treatment period. Further long-term observation may be required to reach the conclusion. CLINICALTRIALS.GOV NUMBER: NCT00144456. Eldecalcitol normalizes, but does not overly suppress, bone turnover regardless of baseline levels of bone turnover markers. Thus, it is unlikely that eldecalcitol treatment will increase the risk of severely suppressed bone turnover and therefore deterioration of bone quality, at least for a treatment duration of 3 years.

Titin is a candidate gene for stroke volume response to endurance training: the HERITAGE Family Study.

PubMed

Rankinen, Tuomo; Rice, Treva; Boudreau, Anik; Leon, Arthur S; Skinner, James S; Wilmore, Jack H; Rao, D C; Bouchard, Claude

2003-09-29

A genome-wide linkage scan for endurance training-induced changes in submaximal exercise stroke volume (DeltaSV50) in the HERITAGE Family Study revealed two chromosomal regions (2q31-q32 and 10p11.2) with at least suggestive evidence of linkage among white families. Here we report a further characterization of the quantitative trait locus (QTL) in chromosome 2q31 and provide evidence that titin (TTN) is likely a candidate gene involved. The original linkage was detected with two markers (D2S335 and D2S1391), and the QTL covered approximately 25 million base pairs (Mb). We added 12 microsatellite markers resulting in an average marker density of one marker per 2.3 Mb. The evidence of linkage increased from P = 0.006 to P = 0.0002 and 0.00002 in the multi- and single-point analyses, respectively. The strongest evidence of linkage was seen with two markers in and near the TTN gene. Transmission/disequilibrium test (TDT) with the same marker set provided evidence for association with one of the TTN markers (D2S385; P = 0.004). TTN is a major contributor to the elasticity of cardiomyocytes and a key regulator of the Frank-Starling mechanism. Since TTN is the largest gene in the human genome, the challenge is to identify the DNA sequence variants contributing to the interindividual differences in cardiac adaptation to endurance training.

Bone Mineral Density in Relation to Metabolic Syndrome Components in Postmenopausal Women With Diabetes Mellitus Type 2

PubMed

Bilić-Ćurčić, Ines; Makarović, Sandra; Mihaljević, Ivan; Franceschi, Maja; Jukić, Tomislav

2017-03-01

Diabetes mellitus type 2 is associated with greater bone mineral density (BMD) due to obesity, although rapid bone loss observed over time could be explained by elevated chronic inflammation. The objective of this study was to investigate the relationship between central adiposity and hyperinsulinemia, as well as inflammation markers with vertebral and femoral BMD and bone turnover markers in postmenopausal women with type 2 diabetes. Femoral and vertebral BMD, osteocalcin, pyrilinks D, beta-CrossLaps (B-CTx), insulin, C-reactive protein (CRP), fibrinogen and plasminogen activator inhibitor-1 (PAI-1) were measured in 114 postmenopausal female patients with diabetes type 2. The patients of similar age, HbA1c levels and diabetes duration were divided into 2 groups based on their body mass index (BMI) values: lower or equal to 27 kg/m(2) (31 patients) and higher than 27 kg/m(2) (83 patients). Lower levels of osteocalcin (p=0.001), B-CTx (p=0.000007) and pyrilinks D (p=0.0365), and higher femoral BMD (p=0.00006), insulin level (p=0.0002), PAI-1 (p=0.00000) and CRP (p=0.002) were found in the overweight group. There were no signifi cant differences in vertebral BMD and fibrinogen. Osteocalcin and B-CTx showed inverse correlation, and femoral BMD positive correlation with waist circumference, insulin level and PAI-1. This suggests that abdominal obesity and hyperinsulinemia as components of the metabolic syndrome could increase femoral BMD by lowering bone rate. In addition, the only inflammation marker linked with femoral BMD was PAI-1, which is associated with increased mineralization of cortical bone in mouse.

Endothelial function and insulin resistance in polycystic ovary syndrome: the effects of medical therapy.

PubMed

Teede, Helena J; Meyer, Caroline; Hutchison, Samantha K; Zoungas, Sophia; McGrath, Barry P; Moran, Lisa J

2010-01-01

To assess the interaction between insulin resistance and endothelial function and the optimal treatment strategy addressing cardiovascular risk in polycystic ovary syndrome. Randomized controlled trial. Controlled clinical study. Overweight age- and body mass index-matched women with polycystic ovary syndrome. Six months metformin (1 g two times per day, n = 36) or oral contraceptive pill (OCP) (35 microg ethinyl E(2)-2 mg cytoproterone acetate, n = 30). Fasting and oral glucose tolerance test glucose and insulin levels, endothelial function (flow-mediated dilation, asymmetric dimethylarginine, plasminogen activator inhibitor-1, von Willebrand factor), inflammatory markers (high-sensitivity C-reactive protein), lipids, and hyperandrogenism. The OCP increased levels of glucose and insulin on oral glucose tolerance test, high-sensitivity C-reactive protein, triglycerides, and sex-hormone binding globulin and decreased levels of low-density lipoprotein cholesterol and T. Metformin decreased levels of fasting insulin, oral glucose tolerance test insulin, high-density lipoprotein cholesterol, and high-sensitivity C-reactive protein. Flow-mediated dilation increased only with metformin (+2.2% +/- 4.8%), whereas asymmetric dimethylarginine decreased equivalently for OCP and metformin (-0.3 +/- 0.1 vs. -0.1 +/- 0.1 mmol/L). Greater decreases in plasminogen activator inhibitor-1 occurred for the OCP than for metformin (-1.8 +/- 1.6 vs. -0.7 +/- 1.7 U/mL). In polycystic ovary syndrome, metformin improves insulin resistance, inflammatory markers, and endothelial function. The OCP worsens insulin resistance and glucose homeostasis, inflammatory markers, and triglycerides and has neutral or positive endothelial effects. The effect of the OCP on cardiovascular risk in polycystic ovary syndrome is unclear. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

High vitamin D3 diet administered during active colitis negatively affects bone metabolism in an adoptive T cell transfer model

PubMed Central

Larmonier, C. B.; McFadden, R.-M. T.; Hill, F. M.; Schreiner, R.; Ramalingam, R.; Besselsen, D. G.; Ghishan, F. K.

2013-01-01

Decreased bone mineral density (BMD) represents an extraintestinal complication of inflammatory bowel disease (IBD). Vitamin D3 has been considered a viable adjunctive therapy in IBD. However, vitamin D3 plays a pleiotropic role in bone modeling and regulates the bone formation-resorption balance, depending on the physiological environment, and supplementation during active IBD may have unintended consequences. We evaluated the effects of vitamin D3 supplementation during the active phase of disease on colonic inflammation, BMD, and bone metabolism in an adoptive IL-10−/− CD4+ T cell transfer model of chronic colitis. High-dose vitamin D3 supplementation for 12 days during established disease had negligible effects on mucosal inflammation. Plasma vitamin D3 metabolites correlated with diet, but not disease, status. Colitis significantly reduced BMD. High-dose vitamin D3 supplementation did not affect cortical bone but led to a further deterioration of trabecular bone morphology. In mice fed a high vitamin D3 diet, colitis more severely impacted bone formation markers (osteocalcin and bone alkaline phosphatase) and increased bone resorption markers, ratio of receptor activator of NF-κB ligand to osteoprotegrin transcript, plasma osteoprotegrin level, and the osteoclast activation marker tartrate-resistant acid phosphatase (ACp5). Bone vitamin D receptor expression was increased in mice with chronic colitis, especially in the high vitamin D3 group. Our data suggest that vitamin D3, at a dose that does not improve inflammation, has no beneficial effects on bone metabolism and density during active colitis or may adversely affect BMD and bone turnover. These observations should be taken into consideration in the planning of further clinical studies with high-dose vitamin D3 supplementation in patients with active IBD. PMID:23639807

High vitamin D3 diet administered during active colitis negatively affects bone metabolism in an adoptive T cell transfer model.

PubMed

Larmonier, C B; McFadden, R-M T; Hill, F M; Schreiner, R; Ramalingam, R; Besselsen, D G; Ghishan, F K; Kiela, P R

2013-07-01

Decreased bone mineral density (BMD) represents an extraintestinal complication of inflammatory bowel disease (IBD). Vitamin D₃ has been considered a viable adjunctive therapy in IBD. However, vitamin D₃ plays a pleiotropic role in bone modeling and regulates the bone formation-resorption balance, depending on the physiological environment, and supplementation during active IBD may have unintended consequences. We evaluated the effects of vitamin D₃ supplementation during the active phase of disease on colonic inflammation, BMD, and bone metabolism in an adoptive IL-10-/- CD4⁺ T cell transfer model of chronic colitis. High-dose vitamin D₃ supplementation for 12 days during established disease had negligible effects on mucosal inflammation. Plasma vitamin D₃ metabolites correlated with diet, but not disease, status. Colitis significantly reduced BMD. High-dose vitamin D₃ supplementation did not affect cortical bone but led to a further deterioration of trabecular bone morphology. In mice fed a high vitamin D₃ diet, colitis more severely impacted bone formation markers (osteocalcin and bone alkaline phosphatase) and increased bone resorption markers, ratio of receptor activator of NF-κB ligand to osteoprotegrin transcript, plasma osteoprotegrin level, and the osteoclast activation marker tartrate-resistant acid phosphatase (ACp5). Bone vitamin D receptor expression was increased in mice with chronic colitis, especially in the high vitamin D₃ group. Our data suggest that vitamin D₃, at a dose that does not improve inflammation, has no beneficial effects on bone metabolism and density during active colitis or may adversely affect BMD and bone turnover. These observations should be taken into consideration in the planning of further clinical studies with high-dose vitamin D₃ supplementation in patients with active IBD.

A Bayesian antedependence model for whole genome prediction.

PubMed

Yang, Wenzhao; Tempelman, Robert J

2012-04-01

Hierarchical mixed effects models have been demonstrated to be powerful for predicting genomic merit of livestock and plants, on the basis of high-density single-nucleotide polymorphism (SNP) marker panels, and their use is being increasingly advocated for genomic predictions in human health. Two particularly popular approaches, labeled BayesA and BayesB, are based on specifying all SNP-associated effects to be independent of each other. BayesB extends BayesA by allowing a large proportion of SNP markers to be associated with null effects. We further extend these two models to specify SNP effects as being spatially correlated due to the chromosomally proximal effects of causal variants. These two models, that we respectively dub as ante-BayesA and ante-BayesB, are based on a first-order nonstationary antedependence specification between SNP effects. In a simulation study involving 20 replicate data sets, each analyzed at six different SNP marker densities with average LD levels ranging from r(2) = 0.15 to 0.31, the antedependence methods had significantly (P < 0.01) higher accuracies than their corresponding classical counterparts at higher LD levels (r(2) > 0. 24) with differences exceeding 3%. A cross-validation study was also conducted on the heterogeneous stock mice data resource (http://mus.well.ox.ac.uk/mouse/HS/) using 6-week body weights as the phenotype. The antedependence methods increased cross-validation prediction accuracies by up to 3.6% compared to their classical counterparts (P < 0.001). Finally, we applied our method to other benchmark data sets and demonstrated that the antedependence methods were more accurate than their classical counterparts for genomic predictions, even for individuals several generations beyond the training data.

Changes in bone density and bone markers in rhythmic gymnasts and ballet dancers: implications for puberty and leptin levels.

PubMed

Muñoz, María Teresa; de la Piedra, Concepción; Barrios, Vicente; Garrido, Guadalupe; Argente, Jesús

2004-10-01

Our aim was to compare physical activity and biochemical markers with bone mineral acquisition in rhythmic gymnasts and ballet dancers. Weight, height, body mass index, nutritional intake, bone age and menstrual histories were analyzed in nine rhythmic gymnasts, twelve ballet dancers and fourteen controls. Bone mineral density (BMD) was assessed by X-ray absorptiometry at the lumbar spine, hip and radius. Bone alkaline phosphatase (bAP) and amino-terminal propeptide of procollagen I (PNIP) in serum and urinary alpha-isomer of the carboxy-terminal telopeptide of collagen I (alpha-CTX) were measured. Bone age was delayed 2 years and mean age at menarche was 15+/-0.9 years in rhythmic gymnasts and 13.7+/-1 years in ballet dancers, compared with 12.5+/-1 years in controls. Trocanteric and femoral neck BMD was significantly higher in rhythmic gymnasts compared with ballet dancers and controls. Right forearm (non-loaded zone) BMD was significantly decreased in rhythmic gymnasts and ballet dancers compared with controls. All subjects had normal bAP and PNIP levels, but the alpha-CTX/creatinine (Cr) ratio was increased in rhythmic gymnasts (P<0.001) with an inverse correlation between right forearm BMD and the alpha-CTX/Cr ratio (r=-0.74, P<0.001). Serum leptin levels were decreased in rhythmic gymnasts and ballet dancers. Rhythmic gymnasts had a positive correlation between right forearm BMD and leptin levels (r=0.85, P<0.001). Decreased bone mass in rhythmic gymnasts could be partially explained by an increase in bone resorption. Serum leptin levels could be implicated in the pubertal delay and be a good marker of bone mass in these subjects.

Cadmium-induced bone effect is not mediated via low serum 1,25-dihydroxy vitamin D

DOE Office of Scientific and Technical Information (OSTI.GOV)

Engstroem, Annette; Skerving, Staffan; Lidfeldt, Jonas

Cadmium is a widespread environmental pollutant, which is associated with increased risk of osteoporosis. It has been proposed that cadmium's toxic effect on bone is exerted via impaired activation of vitamin D, secondary to the kidney effects. To test this, we assessed the association of cadmium-induced bone and kidney effects with serum 1,25-dihydroxyvitamin D (1,25(OH){sub 2}D); measured by enzyme immunoassay. For the assessment, we selected 85 postmenopausal women, based on low (0.14-0.39 {mu}g/L) or high (0.66-2.1 {mu}g/L) urinary cadmium, within a cross-sectional population-based women's health survey in Southern Sweden. We also measured 25-hydroxy vitamin D, cadmium in blood, bone mineralmore » density and several markers of bone remodeling and kidney effects. Although there were clear differences in both kidney and bone effect markers between women with low and high cadmium exposure, the 1,25(OH){sub 2}D concentrations were not significantly different (median, 111 pmol/L (5-95th percentile, 67-170 pmol/L) in low- and 125 pmol/L (66-200 pmol/L) in high-cadmium groups; p=0.08). Also, there was no association between 1,25(OH){sub 2}D and markers of bone or kidney effects. It is concluded that the low levels of cadmium exposure present in the studied women, although high enough to be associated with lower bone mineral density and increased bone resorption, were not associated with lower serum concentrations of 1,25(OH){sub 2}D. Hence, decreased circulating levels of 1,25(OH){sub 2}D are unlikely to be the proposed link between cadmium-induced effects on kidney and bone.« less

Discovery and mapping of a new expressed sequence tag-single nucleotide polymorphism and simple sequence repeat panel for large-scale genetic studies and breeding of Theobroma cacao L.

PubMed Central

Allegre, Mathilde; Argout, Xavier; Boccara, Michel; Fouet, Olivier; Roguet, Yolande; Bérard, Aurélie; Thévenin, Jean Marc; Chauveau, Aurélie; Rivallan, Ronan; Clement, Didier; Courtois, Brigitte; Gramacho, Karina; Boland-Augé, Anne; Tahi, Mathias; Umaharan, Pathmanathan; Brunel, Dominique; Lanaud, Claire

2012-01-01

Theobroma cacao is an economically important tree of several tropical countries. Its genetic improvement is essential to provide protection against major diseases and improve chocolate quality. We discovered and mapped new expressed sequence tag-single nucleotide polymorphism (EST-SNP) and simple sequence repeat (SSR) markers and constructed a high-density genetic map. By screening 149 650 ESTs, 5246 SNPs were detected in silico, of which 1536 corresponded to genes with a putative function, while 851 had a clear polymorphic pattern across a collection of genetic resources. In addition, 409 new SSR markers were detected on the Criollo genome. Lastly, 681 new EST-SNPs and 163 new SSRs were added to the pre-existing 418 co-dominant markers to construct a large consensus genetic map. This high-density map and the set of new genetic markers identified in this study are a milestone in cocoa genomics and for marker-assisted breeding. The data are available at http://tropgenedb.cirad.fr. PMID:22210604

Immunoscore encompassing CD3+ and CD8+ T cell densities in distant metastasis is a robust prognostic marker for advanced colorectal cancer

PubMed Central

Kwak, Yoonjin; Koh, Jiwon; Kim, Duck-Woo; Kang, Sung-Bum; Kim, Woo Ho; Lee, Hye Seung

2016-01-01

Background The immunoscore (IS), an index based on the density of CD3+ and CD8+ tumor-infiltrating lymphocytes (TILs) in the tumor center (CT) and invasive margin (IM), has gained considerable attention as a prognostic marker. Tumor-associated macrophages (TAMs) have also been reported to have prognostic value. However, its clinical significance has not been fully clarified in patients with advanced CRC who present with distant metastases. Methods The density of CD3+, CD4+, CD8+, FOXP3+, CD68+, and CD163+ immune cells within CRC tissue procured from three sites–the primary CT, IM, and distant metastasis (DM)–was determined using immunohistochemistry and digital image analyzer (n=196). The IS was obtained by quantifying the densities of CD3+ and CD8+ TILs in the CT and IM. IS-metastatic and IS-macrophage–additional IS models designed in this study–were obtained by adding the score of CD3 and CD8 in DM and the score of CD163 in primary tumors (CT and IM), respectively, to the IS. Result Higher IS, IS-metastatic, and IS-macrophage values were significantly correlated with better prognosis (p=0.020, p≤0.001, and p=0.005, respectively). Multivariate analysis revealed that only IS-metastatic was an independent prognostic marker (p=0.012). No significant correlation was observed between KRAS mutation and three IS models. However, in the subgroup analysis, IS-metastatic showed a prognostic association regardless of the KRAS mutational status. Conclusion IS is a reproducible method for predicting the survival of patients with advanced CRC. Additionally, an IS including the CD3+ and CD8+ TIL densities at DM could be a strong prognostic marker for advanced CRC. PMID:27835889

The influence of vegan diet on bone mineral density and biochemical bone turnover markers.

PubMed

Ambroszkiewicz, Jadwiga; Klemarczyk, Witold; Gajewska, Joanna; Chełchowska, Magdalena; Franek, Edward; Laskowska-Klita, Teresa

2010-01-01

Vegetarian diets can be healthy when they are well balanced and if a variety of foods is consumed. However, elimination of animal products from the diet (vegan diets) decreases the intake of some essential nutrients and may influence the bone metabolism. This is especially important in childhood and adolescence, when growth and bone turnover are most intensive. The aim of the study was to assess the effect of vegan diet on bone density (BMD) density and serum concentrations of bone metabolism markers. We examined a family on vegan diet which consisted of parents and two children. Dietary constituents were analysed using a nutritional program. Total and regional BMD were measured by dual-energy X-ray absorptiometry. Concentrations of calcium and phosphate in serum obtained from fasting patients were determined by colorimetric methods, 25-hydroxyvitamin D by the chemiluminescence method and bone turnover markers by specific enzyme immunoassays. In studied vegans, the dietary intake of phosphate was adequate while calcium and vitamin D were below the recommended range. Concentrations of calcium, phosphate and bone turnover markers in the serum of all subjects were within the physiological range, but 25-hydroxyvitamin D level was low. Age-matched Z-score total BMD was between -0.6 and 0.3 in adults, however in children it was lower (-0.9 and -1.0). Z-score BMD lumbar spine (L2-L4) was between -0.9 to -1.9 in parents and -1.5 to -1.7 in children. Our results suggest that an inadequate dietary intake of calcium and vitamin D may impair the bone turnover rate and cause a decrease in bone mineral density in vegans. The parameters of bone density and bone metabolism should be monitored in vegans, especially children, in order to prevent bone abnormalities.

The gene expression pattern induced by high plating density in cultured bovine and buffalo granulosa cells might be regulated by specific miRNA species

PubMed Central

YENUGANTI, Vengala Rao; BADDELA, Vijay Simha; BAUFELD, Anja; SINGH, Dheer; VANSELOW, Jens

2015-01-01

Precise regulation of cell type-specific gene expression profiles precedes the profound morphological reorganization of somatic cell layers during folliculogenesis, ovulation and luteinization. Cell culture models are essential to the study of corresponding molecular mechanisms of gene regulation. In a recent study, it was shown that an increased cell plating density can largely change gene expression profiles of cultured bovine granulosa cells. In our present study, we comparatively analyzed cell plating density effects on cultured bovine and buffalo granulosa cells. Cells were isolated from small- to medium-sized follicles (2–6 mm) and cultured under serum-free conditions at different plating densities. The abundance of selected marker transcripts and associated miRNA candidates was determined by quantitative real-time RT-PCR. We found in both species that the abundance of CYP19A1, CCNE1 and PCNA transcripts was remarkably lower at a high plating density, whereas VNN2 and RGS2 transcripts significantly increased. In contrast, putative regulators of CYP19A1, miR-378, miR-106a and let-7f were significantly higher in both species or only in buffalo, respectively. Also miR-15a, a regulator of CCNE1, was upregulated in both species. Thus, increased plating density induced similar changes of mRNA and miRNA expression in granulosa cells from buffalo and cattle. From these data, we conclude that specific miRNA species might be involved in the observed density-induced gene regulation. PMID:25740097

A toxicity profile of osteoprotegerin in the cynomolgus monkey.

PubMed

Smith, Brenda B; Cosenza, Mary Ellen; Mancini, Audrey; Dunstan, Colin; Gregson, Richard; Martin, Steven W; Smith, Susan Y; Davis, Harold

2003-01-01

Osteoprotegerin (OPG) is a novel secreted glycoprotein of the tumor necrosis factor (TNF) receptor superfamily that acts as an antiresorptive agent inhibiting osteoclast maturation. OPG acts by competitively inhibiting the association of the OPG ligand with the RANK receptor on osteoclasts and osteoclast precursors. This inhibition of osteoclasts can lead to excess accumulation of newly synthesized bone and cartilage in vivo. The purpose of this study was to investigate the potential toxicity of a human recombinant form of OPG in the young cynomolgus monkey. OPG was administered by intravenous (i.v.) or subcutaneous (s.c.) injection three times per week for either 4 or 13 weeks. There were no deaths during the study, no clinical signs related to treatment, no effect on body weight, appetence, or ophthalmology. No toxicologically relevant changes in routine laboratory investigations, organ weights, or gross or histopathological findings were observed. Serum ionized calcium and phosphorus were decreased at all dose levels. Evaluations were performed to monitor biochemical markers of bone resorption (N-telopeptide [NTx], deoxypyridinoline [DPD]), bone formation (skeletal alkaline phosphatase [sALP], osteocalcin [OC]), parathyroid hormone [PTH], and bone density of the proximal tibia and distal radius in vivo. Dose-related decreases in NTx and/or DPD were observed at each dose level, with up to a 90% decrease in NTx noted for animals treated i.v. or s.c. at 15 mg/kg. Similar decreases were observed for sALP and OC. PTH was increased for animals treated at 5 and 15 mg/kg (i.v. or s.c.). Trabecular bone density was increased for the majority of males and females treated i.v. or s.c. at 15 mg/kg and males treated i.v. at 5 mg/kg. Microscopic examination of the sternebrae revealed corresponding increases in bone. Decreases in markers of bone turnover, and corresponding increases in bone density, were consistent with the pharmacological action of OPG as an osteoclast inhibitor. The no-observable-adverse-effect level (NOAEL) of OPG was 15 mg/kg.

Development of a dense SNP-based linkage map of an apple rootstock progeny using the Malus Infinium whole genome genotyping array.

PubMed

Antanaviciute, Laima; Fernández-Fernández, Felicidad; Jansen, Johannes; Banchi, Elisa; Evans, Katherine M; Viola, Roberto; Velasco, Riccardo; Dunwell, Jim M; Troggio, Michela; Sargent, Daniel J

2012-05-25

A whole-genome genotyping array has previously been developed for Malus using SNP data from 28 Malus genotypes. This array offers the prospect of high throughput genotyping and linkage map development for any given Malus progeny. To test the applicability of the array for mapping in diverse Malus genotypes, we applied the array to the construction of a SNP-based linkage map of an apple rootstock progeny. Of the 7,867 Malus SNP markers on the array, 1,823 (23.2%) were heterozygous in one of the two parents of the progeny, 1,007 (12.8%) were heterozygous in both parental genotypes, whilst just 2.8% of the 921 Pyrus SNPs were heterozygous. A linkage map spanning 1,282.2 cM was produced comprising 2,272 SNP markers, 306 SSR markers and the S-locus. The length of the M432 linkage map was increased by 52.7 cM with the addition of the SNP markers, whilst marker density increased from 3.8 cM/marker to 0.5 cM/marker. Just three regions in excess of 10 cM remain where no markers were mapped. We compared the positions of the mapped SNP markers on the M432 map with their predicted positions on the 'Golden Delicious' genome sequence. A total of 311 markers (13.7% of all mapped markers) mapped to positions that conflicted with their predicted positions on the 'Golden Delicious' pseudo-chromosomes, indicating the presence of paralogous genomic regions or mis-assignments of genome sequence contigs during the assembly and anchoring of the genome sequence. We incorporated data for the 2,272 SNP markers onto the map of the M432 progeny and have presented the most complete and saturated map of the full 17 linkage groups of M. pumila to date. The data were generated rapidly in a high-throughput semi-automated pipeline, permitting significant savings in time and cost over linkage map construction using microsatellites. The application of the array will permit linkage maps to be developed for QTL analyses in a cost-effective manner, and the identification of SNPs that have been assigned erroneous positions on the 'Golden Delicious' reference sequence will assist in the continued improvement of the genome sequence assembly for that variety.

Overcoming resistance to bisphosphonates through the administration of alfacalcidol: results of a 1-year, open follow-up study.

PubMed

Gaál, János; Bender, Tamás; Varga, József; Horváth, Irén; Kiss, Judit; Somogyi, Péter; Surányi, Péter

2009-11-01

This study intended to determine whether the replacement of vitamin D3 with alfacalcidol results in any bone mineral density (BMD) increase in 76 patients unresponsive to the combination of alendronate and conventional vitamin D3 treatment. In these patients the conventional vitamin D3 had been replaced with alfacalcidol (0.5 μg/day), and then the patients were followed up for a year. After treatment for 1 year, Wilcoxon test revealed a small but statistically significant (P < 0.001) increase in the BMD values of the forearm and lumbar vertebrae, in the serum calcium and urinary calcium/creatinine ratio in first-voided morning urine. However, the serum alkaline phosphatase activity, phosphorus, parathormone, osteocalcin levels and the urinary d-pyr/creatinine ratio decreased significantly (P < 0.001). As suggested by our results, combination therapy with alendronate and alfacalcidol increases bone density and improves the biochemical markers of bone turnover, without any substantial increase in the incidence of adverse effects.

Osteoporosis, Fractures, and Diabetes

PubMed Central

2014-01-01

It is well established that osteoporosis and diabetes are prevalent diseases with significant associated morbidity and mortality. Patients with diabetes mellitus have an increased risk of bone fractures. In type 1 diabetes, the risk is increased by ∼6 times and is due to low bone mass. Despite increased bone mineral density (BMD), in patients with type 2 diabetes the risk is increased (which is about twice the risk in the general population) due to the inferior quality of bone. Bone fragility in type 2 diabetes, which is not reflected by bone mineral density, depends on bone quality deterioration rather than bone mass reduction. Thus, surrogate markers and examination methods are needed to replace the insensitivity of BMD in assessing fracture risks of T2DM patients. One of these methods can be trabecular bone score. The aim of the paper is to present the present state of scientific knowledge about the osteoporosis risk in diabetic patient. The review also discusses the possibility of problematic using the study conclusions in real clinical practice. PMID:25050121

A Linkage Map of the Asian Tiger Mosquito (Aedes albopictus) Based on cDNA Markers

PubMed Central

Sutherland, Ian W.; Mori, Akio; Montgomery, John; Fleming, Karen L.; Anderson, Jennifer M.; Valenzuela, Jesus G.; Severson, David W.

2011-01-01

The Asian tiger mosquito, Aedes (Stegomyia) albopictus (Skuse), is an important vector of a number of arboviruses, and populations exhibit extreme variation in adaptive traits such as egg diapause, cold hardiness, and autogeny (ability to mature a batch of eggs without blood feeding). The genetic basis of some of these traits has been established, but lack of a high-resolution linkage map has prevented in-depth genetic analyses of the genes underlying these complex traits. We report here on the breeding of 4 F1 intercross mapping families and the use of these to locate 35 cDNA markers to the A. albopictus linkage map. The present study increases the number of markers on the A. albopictus cDNA linkage map from 38 to 73 and the density of markers from 1 marker/5.7 cM to 1 marker/2.9 cM and adds 9, 16, and 10 markers to the 3 linkage groups, respectively. The overall lengths of the 3 linkage groups are 64.5, 76.5, and 71.6 cM, respectively, for a combined length of 212.6 cM. Despite conservation in the order of most genes among the 4 families and a previous mapping family, we found substantial heterogeneity in the amount of recombination among markers. This was most marked in linkage group I, which varied between 16.7 and 69.3 cM. A map integrating the results from these 4 families with an earlier cDNA linkage map is presented. PMID:21148282

Construction of Ultradense Linkage Maps with Lep-MAP2: Stickleback F2 Recombinant Crosses as an Example

PubMed Central

Rastas, Pasi; Calboli, Federico C. F.; Guo, Baocheng; Shikano, Takahito; Merilä, Juha

2016-01-01

High-density linkage maps are important tools for genome biology and evolutionary genetics by quantifying the extent of recombination, linkage disequilibrium, and chromosomal rearrangements across chromosomes, sexes, and populations. They provide one of the best ways to validate and refine de novo genome assemblies, with the power to identify errors in assemblies increasing with marker density. However, assembly of high-density linkage maps is still challenging due to software limitations. We describe Lep-MAP2, a software for ultradense genome-wide linkage map construction. Lep-MAP2 can handle various family structures and can account for achiasmatic meiosis to gain linkage map accuracy. Simulations show that Lep-MAP2 outperforms other available mapping software both in computational efficiency and accuracy. When applied to two large F2-generation recombinant crosses between two nine-spined stickleback (Pungitius pungitius) populations, it produced two high-density (∼6 markers/cM) linkage maps containing 18,691 and 20,054 single nucleotide polymorphisms. The two maps showed a high degree of synteny, but female maps were 1.5–2 times longer than male maps in all linkage groups, suggesting genome-wide recombination suppression in males. Comparison with the genome sequence of the three-spined stickleback (Gasterosteus aculeatus) revealed a high degree of interspecific synteny with a low frequency (<5%) of interchromosomal rearrangements. However, a fairly large (ca. 10 Mb) translocation from autosome to sex chromosome was detected in both maps. These results illustrate the utility and novel features of Lep-MAP2 in assembling high-density linkage maps, and their usefulness in revealing evolutionarily interesting properties of genomes, such as strong genome-wide sex bias in recombination rates. PMID:26668116

Modulation of chondrogenic differentiation of human mesenchymal stem cells in jellyfish collagen scaffolds by cell density and culture medium.

PubMed

Pustlauk, W; Paul, B; Brueggemeier, S; Gelinsky, M; Bernhardt, A

2017-06-01

Studies on tissue-engineering approaches for the regeneration of traumatized cartilage focus increasingly on multipotent human mesenchymal stem cells (hMSCs) as an alternative to autologous chondrocytes. The present study applied porous scaffolds made of collagen from the jellyfish Rhopilema esculentum for the in vitro chondrogenic differentiation of hMSCs. Culture conditions in those scaffolds differ from conditions in high-density pellet cultures, making a re-examination of these data necessary. We systematically investigated the influence of seeding density, basic culture media [Dulbecco's modified Eagle's medium (DMEM), α-minimum essential medium (α-MEM)] with varying glucose content and supplementation with fetal calf serum (FCS) or bovine serum albumin (BSA) on the chondrogenic differentiation of hMSCs. Gene expression analyses of selected markers for chondrogenic differentiation and hypertrophic development were conducted. Furthermore, the production of cartilage extracellular matrix (ECM) was analysed by quantification of sulphated glycosaminoglycan and collagen type II contents. The strongest upregulation of chondrogenic markers, along with the highest ECM deposition was observed in scaffolds seeded with 2.4 × 10 6 cells/cm 3 after cultivation in high-glucose DMEM and 0.125% BSA. Lower seeding densities compared to high-density pellet cultures were sufficient to induce in vitro chondrogenic differentiation of hMSCs in collagen scaffolds, which reduces the amount of cells required for the seeding of scaffolds and thus the monolayer expansion period. Furthermore, examination of the impact of FCS and α-MEM on chondrogenic MSC differentiation is an important prerequisite for the development of an osteochondral medium for simultaneous osteogenic and chondrogenic differentiation in biphasic scaffolds for osteochondral tissue regeneration. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Combining different marker densities in genomic evaluation

USDA-ARS?s Scientific Manuscript database

Accurate genomic evaluations are less costly if many animals are genotyped at less than the highest density and their missing genotypes filled using haplotypes. Mixed density files for 45,870 animals were examined by reducing half of young animal or all animal genotypes from the observed 43,385 mark...

Protein and glycomic plasma markers for early detection of adenoma and colon cancer.

PubMed

Rho, Jung-Hyun; Ladd, Jon J; Li, Christopher I; Potter, John D; Zhang, Yuzheng; Shelley, David; Shibata, David; Coppola, Domenico; Yamada, Hiroyuki; Toyoda, Hidenori; Tada, Toshifumi; Kumada, Takashi; Brenner, Dean E; Hanash, Samir M; Lampe, Paul D

2018-03-01

To discover and confirm blood-based colon cancer early-detection markers. We created a high-density antibody microarray to detect differences in protein levels in plasma from individuals diagnosed with colon cancer <3 years after blood was drawn (ie, prediagnostic) and cancer-free, matched controls. Potential markers were tested on plasma samples from people diagnosed with adenoma or cancer, compared with controls. Components of an optimal 5-marker panel were tested via immunoblotting using a third sample set, Luminex assay in a large fourth sample set and immunohistochemistry (IHC) on tissue microarrays. In the prediagnostic samples, we found 78 significantly (t-test) increased proteins, 32 of which were confirmed in the diagnostic samples. From these 32, optimal 4-marker panels of BAG family molecular chaperone regulator 4 (BAG4), interleukin-6 receptor subunit beta (IL6ST), von Willebrand factor (VWF) and CD44 or epidermal growth factor receptor (EGFR) were established. Each panel member and the panels also showed increases in the diagnostic adenoma and cancer samples in independent third and fourth sample sets via immunoblot and Luminex, respectively. IHC results showed increased levels of BAG4, IL6ST and CD44 in adenoma and cancer tissues. Inclusion of EGFR and CD44 sialyl Lewis-A and Lewis-X content increased the panel performance. The protein/glycoprotein panel was statistically significantly higher in colon cancer samples, characterised by a range of area under the curves from 0.90 (95% CI 0.82 to 0.98) to 0.86 (95% CI 0.83 to 0.88), for the larger second and fourth sets, respectively. A panel including BAG4, IL6ST, VWF, EGFR and CD44 protein/glycomics performed well for detection of early stages of colon cancer and should be further examined in larger studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Sunflower Hybrid Breeding: From Markers to Genomic Selection

PubMed Central

Dimitrijevic, Aleksandra; Horn, Renate

2018-01-01

In sunflower, molecular markers for simple traits as, e.g., fertility restoration, high oleic acid content, herbicide tolerance or resistances to Plasmopara halstedii, Puccinia helianthi, or Orobanche cumana have been successfully used in marker-assisted breeding programs for years. However, agronomically important complex quantitative traits like yield, heterosis, drought tolerance, oil content or selection for disease resistance, e.g., against Sclerotinia sclerotiorum have been challenging and will require genome-wide approaches. Plant genetic resources for sunflower are being collected and conserved worldwide that represent valuable resources to study complex traits. Sunflower association panels provide the basis for genome-wide association studies, overcoming disadvantages of biparental populations. Advances in technologies and the availability of the sunflower genome sequence made novel approaches on the whole genome level possible. Genotype-by-sequencing, and whole genome sequencing based on next generation sequencing technologies facilitated the production of large amounts of SNP markers for high density maps as well as SNP arrays and allowed genome-wide association studies and genomic selection in sunflower. Genome wide or candidate gene based association studies have been performed for traits like branching, flowering time, resistance to Sclerotinia head and stalk rot. First steps in genomic selection with regard to hybrid performance and hybrid oil content have shown that genomic selection can successfully address complex quantitative traits in sunflower and will help to speed up sunflower breeding programs in the future. To make sunflower more competitive toward other oil crops higher levels of resistance against pathogens and better yield performance are required. In addition, optimizing plant architecture toward a more complex growth type for higher plant densities has the potential to considerably increase yields per hectare. Integrative approaches combining omic technologies (genomics, transcriptomics, proteomics, metabolomics and phenomics) using bioinformatic tools will facilitate the identification of target genes and markers for complex traits and will give a better insight into the mechanisms behind the traits. PMID:29387071

Serum resistin correlates with central obesity but weakly with insulin resistance in Chinese children and adolescents.

PubMed

Li, M; Fisette, A; Zhao, X-Y; Deng, J-Y; Mi, J; Cianflone, K

2009-04-01

Resistin has been linked with obesity and hypothesized as a potential marker of insulin resistance in addition to being linked with acute inflammation. However, these links are still highly controversial in humans. Our goal was to examine resistin levels in relation to obesity, insulin resistance and inflammation markers in a large population of Asian children and adolescents. Children and adolescents (n=3472) aged 6-18 years, boys (n=1765) and girls (n=1707), were assessed for body size parameters, pubertal development, blood lipids, glucose, insulin, resistin, C-reactive protein (CRP), adiponectin and complement C3 (C3) levels. Resistin increased with central obesity in both genders but not with simple adiposity in boys. Several markers associated with central obesity correlated in a gender-specific fashion with plasma resistin. Waist circumference, fat-mass percentage, waist-to-height ratio and body mass index (BMI) positively correlated with resistin in both genders. Blood lipids such as triglycerides, nonesterified fatty acids (NEFA) and low-density lipoprotein cholesterol, diastolic and systolic blood pressure correlated positively with resistin in boys. NEFA, high-density lipoprotein cholesterol (negatively) and inflammation markers, such as CRP and C3, positively correlated with resistin in girls. There was no correlation between resistin and adiponectin, and no association of adiponectin with resistin quintiles in either boys or girls. In both boys and girls, resistin tended to decrease with age, with girls having higher levels than boys. Few indices of insulin resistance were linked with plasma resistin in either gender. In this population, plasma resistin levels are a weak biochemical marker of metabolic dysfunction defined by central obesity, adiposity and inflammation and does not predict insulin resistance. Only a small proportion of resistin variation can be explained by factors related to metabolic syndrome, suggesting that resistin is not strongly implicated in a concentration-dependent fashion in any of the examined pathologies.

Correlations of chemokine CXCL16 and TNF-α with coronary atherosclerotic heart disease.

PubMed

Xing, Jieyong; Liu, Yanshao; Chen, Tao

2018-01-01

This study determined the correlations of CXC ligand 16 (CXCL16) and tumor necrosis factor-α (TNF-α) levels with coronary atherosclerotic heart disease (CAHD) and screened for new clinical markers for the prognosis and treatment of the disease. Eighty patients with coronary heart disease and 50 healthy subjects were enrolled into a CAHD or healthy control group, respectively. Computed tomography (CT) coronary angiography and Gensini integral were used to classify plaques and evaluate patients with coronary heart disease. The serum levels of CXCL16 and TNF-α of subjects in each group were detected by enzyme-linked immunosorbent assays (ELISA), and the correlation between levels and clinical markers (such as blood pressure, glucose, lipid and heart rate) and the severity of disease were analyzed. Our results showed the serum levels of CXCL16 and TNF-α were significantly higher in the CAHD group than those in the CK group. The serum CXCL16 levels of the CAHD group patients with plaques were distinctly higher than those of the CADH group patients without plaques, but there were no significant difference in serum TNF-α levels between these two groups of patients. The level of CXCL16 had a significantly positive correlation with the severity of disease, but there was no significant correlation between TNF-α level and the severity of disease. Also, there was no significant correlation between the CXCL16 levels and blood pressure, blood glucose, heart rate, total cholesterol, triglyceride or high-density lipoprotein cholesterol, but there was a clear correlation with the low-density lipoprotein cholesterol. Finally no significant correlations were found between TNF-α levels and each of the clinical markers studied. Based on our findings, the levels of CXCL16 and TNF-α in the patients with coronary heart disease were abnormally increased and the level of CXCL16 correlated closely with the severity of disease. These markers seem to be reliable biological markers for prognosis and disease evaluation in coronary heart disease patients.

Low RMRratio as a Surrogate Marker for Energy Deficiency, the Choice of Predictive Equation Vital for Correctly Identifying Male and Female Ballet Dancers at Risk.

PubMed

Staal, Sarah; Sjödin, Anders; Fahrenholtz, Ida; Bonnesen, Karen; Melin, Anna Katarina

2018-06-22

Ballet dancers are reported to have an increased risk for energy deficiency with or without disordered eating behavior. A low ratio between measured ( m ) and predicted ( p ) resting metabolic rate (RMR ratio  < 0.90) is a recognized surrogate marker for energy deficiency. We aimed to evaluate the prevalence of suppressed RMR using different methods to calculate p RMR and to explore associations with additional markers of energy deficiency. Female (n = 20) and male (n = 20) professional ballet dancers, 19-35 years of age, were enrolled. m RMR was assessed by respiratory calorimetry (ventilated open hood). p RMR was determined using the Cunningham and Harris-Benedict equations, and different tissue compartments derived from whole-body dual-energy X-ray absorptiometry assessment. The protocol further included assessment of body composition and bone mineral density, blood pressure, disordered eating (Eating Disorder Inventory-3), and for females, the Low Energy Availability in Females Questionnaire. The prevalence of suppressed RMR was generally high but also clearly dependent on the method used to calculate p RMR, ranging from 25% to 80% in males and 35% to 100% in females. Five percent had low bone mineral density, whereas 10% had disordered eating and 25% had hypotension. Forty percent of females had elevated Low Energy Availability in Females Questionnaire score and 50% were underweight. Suppressed RMR was associated with elevated Low Energy Availability in Females Questionnaire score in females and with higher training volume in males. In conclusion, professional ballet dancers are at risk for energy deficiency. The number of identified dancers at risk varies greatly depending on the method used to predict RMR when using RMR ratio as a marker for energy deficiency.

Heat Induction of Prophage φ105 in Bacillus subtilis: Replication of the Bacterial and Bacteriophage Genomes

PubMed Central

Armentrout, Richard W.; Rutberg, Lars

1971-01-01

A temperature-inducible mutant of temperate Bacillus bacteriophage φ105 was isolated and used to lysogenize a thymine-requiring strain of Bacillus subtilis 168. Synthesis of phage and bacterial deoxyribonucleic acid (DNA) was studied by sucrose gradient centrifugation and density equilibrium centrifugation of DNA extracted from induced bacteria. The distribution of DNA in the gradients was measured by differential isotope and density labeling of DNA before and after induction and by measuring the biological activity of the DNA in genetic transformation, in rescue of phage markers, and in infectivity assays. At early times after induction, but after at least one round of replication, phage DNA remains associated with high-molecular-weight DNA, whereas, later in the infection, phage DNA is associated with material of decreasing molecular weight. Genetic linkage between phage and bacterial markers can be demonstrated in replicated DNA from induced cells. Prophage induction is shown to affect replication of the bacterial chromosome. The overall rate of replication of prelabeled bacterial DNA is identical in temperature-induced lysogenics and in “mock-induced” wild-type φ105 lysogenics. The rate of replication of the bacterial marker phe-1 (and also of nia-38), located close to the prophage in direction of the terminus of the bacterial chromosome, is increased in induced cells, however, relative to other bacterial markers tested. In temperature-inducible lysogenics, where the prophage also carries a ts mutation which blocks phage DNA synthesis, replication of both phage and bacterial DNA stops after about 50% of the phage DNA has replicated once. The results of these experiments suggest that the prophage is not initially excised in induced cells, but rather it is specifically replicated in situ together with adjacent parts of the bacterial chromosome. PMID:5002012

Improved recovery of functionally active eosinophils and neutrophils using novel immunomagnetic technology.

PubMed

Son, Kiho; Mukherjee, Manali; McIntyre, Brendan A S; Eguez, Jose C; Radford, Katherine; LaVigne, Nicola; Ethier, Caroline; Davoine, Francis; Janssen, Luke; Lacy, Paige; Nair, Parameswaran

2017-10-01

Clinically relevant and reliable reports derived from in vitro research are dependent on the choice of cell isolation protocols adopted between different laboratories. Peripheral blood eosinophils are conventionally isolated using density-gradient centrifugation followed by immunomagnetic selection (positive/negative) while neutrophils follow a more simplified dextran-sedimentation methodology. With the increasing sophistication of molecular techniques, methods are now available that promise protocols with reduced user-manipulations, improved efficiency, and better yield without compromising the purity of enriched cell populations. These recent techniques utilize immunomagnetic particles with multiple specificities against differential cell surface markers to negatively select non-target cells from whole blood, greatly reducing the cost/time taken to isolate granulocytes. Herein, we compare the yield efficiencies, purity and baseline activation states of eosinophils/neutrophils isolated using one of these newer protocols that use immunomagnetic beads (MACSxpress isolation) vs. the standard isolation procedures. The study shows that the MACSxpress method consistently allowed higher yields per mL of peripheral blood compared to conventional methods (P<0.001, n=8, Wilcoxon paired test), with high isolation purities for both eosinophils (95.0±1.7%) and neutrophils (94.2±10.1%) assessed by two methods: Wright's staining and flow cytometry. In addition, enumeration of CD63 + (marker for eosinophil activation) and CD66b + (marker for neutrophil activation) cells within freshly isolated granulocytes, respectively, confirmed that conventional protocols using density-gradient centrifugation caused cellular activation of the granulocytes at baseline compared to the MACSxpress method. In conclusion, MACSxpress isolation kits were found to be superior to conventional techniques for consistent purifications of eosinophils and neutrophils that were suitable for activation assays involving degranulation markers. Copyright © 2017 Elsevier B.V. All rights reserved.

Biochemical Markers of Bone Turnover in Percutaneous Vertebroplasty for Osteoporotic Compression Fracture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Komemushi, Atsushi, E-mail: kome64@yo.rim.or.jp; Tanigawa, Noboru; Kariya, Shuji

Purpose. To evaluate relationships between biochemical markers of bone turnover, bone mineral density, and new compression fractures following vertebroplasty. Methods. Initially, we enrolled 30 consecutive patients with vertebral compression fractures caused by osteoporosis. Twenty-three of the 30 patients visited our hospital for follow-up examinations for more than 4 weeks after vertebroplasty. The patients were divided into two groups: patients with new fractures (group F) and patients with no new fractures (group N). We analyzed differences in the following parameters between these two groups: serum bone alkaline phosphatase, urinary crosslinked N-telopeptide of type I collagen, urinary deoxypyridinoline, and bone mineral density.more » Next, the patients were divided into another two groups: patients with higher risk (group H: urinary crosslinked N-telopeptide of type I collagen >54.3 nmol BCE/mmol Cr or urinary deoxypyridinoline >7.6 nmol/mmol Cr, and serum bone alkaline phosphatase <29.0 U/l) and patients with lower risk (group L). We analyzed the difference in the rate of new fractures between these two groups. Results. We identified 9 new fractures in 7 patients. There were no significant differences between groups F and N. We identified 5 new fractures in 3 of the 4 patients in group H, and 4 new fractures in 4 of the 19 patients in group L. There was a significant difference in the rate of new fractures between groups H and L. Conclusions. A combination of high levels of bone resorption markers and normal levels of bone formation markers may be associated with increased risk of new recurrent fractures after percutaneous vertebroplasty.« less

Higher gamma-aminobutyric acid neuron density in the white matter of orbital frontal cortex in schizophrenia.

PubMed

Joshi, Dipesh; Fung, Samantha J; Rothwell, Alice; Weickert, Cynthia Shannon

2012-11-01

In the orbitofrontal cortex (OFC), reduced gray matter volume and reduced glutamic acid decarboxylase 67kDa isoform (GAD67) messenger (m)RNA are found in schizophrenia; however, how these alterations relate to developmental pathology of interneurons is unclear. The present study therefore aimed to determine if increased interstitial white matter neuron (IWMN) density exists in the OFC; whether gamma-aminobutyric acid (GABA)ergic neuron density in OFC white matter was altered; and how IWMN density may be related to an early-expressed inhibitory neuron marker, Dlx1, in OFC gray matter in schizophrenia. IWMN densities were determined (38 schizophrenia and 38 control subjects) for neuronal nuclear antigen (NeuN+) and 65/67 kDa isoform of glutamic acid decarboxylase immunopositive (GAD65/67+) neurons. In situ hybridization was performed to determine Dlx1 and GAD67 mRNA expression in the OFC gray matter. NeuN and GAD65/67 immunopositive cell density was significantly increased in the superficial white matter in schizophrenia. Gray matter Dlx1 and GAD67 mRNA expression were reduced in schizophrenia. Dlx1 mRNA levels were negatively correlated with GAD65/67 IWMN density. Our study provides evidence that pathology of IWMNs in schizophrenia includes GABAergic interneurons and that increased IWMN density may be related to GABAergic deficits in the overlying gray matter. These findings provide evidence at the cellular level that the OFC is a site of pathology in schizophrenia and support the hypothesis that inappropriate migration of cortical inhibitory interneurons occurs in schizophrenia. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

A sequencing-based linkage map of cucumber

USDA-ARS?s Scientific Manuscript database

Genetic maps are important tools for molecular breeding, gene cloning, and study of meiotic recombination. In cucumber (Cucumis sativus L.), the marker density, resolution and genome coverage of previously developed genetic maps using PCR-based molecular markers are relatively low. In this study we ...

Predicting bone mineral acquisition during puberty: data from a 3-year follow-up study in Hamamatsu, Japan.

PubMed

Kouda, Katsuyasu; Ohara, Kumiko; Nakamura, Harunobu; Fujita, Yuki; Iki, Masayuki

2017-03-01

Although most adult bone mass is acquired before adolescence, only a few studies have assessed bone turnover markers in children. Thus, the utility of bone markers to evaluate and predict bone mineral accrual in children is unclear. The present study assessed the association between serum bone markers at 11 years of age and subsequent changes in bone gain. Information on bone minerals and bone markers at baseline and at the 3-year follow-up were obtained from 121 children who registered as fifth-grade students in 2010, in Hamamatsu, Japan. Whole-body bone mineral content (WBBMC) and whole-body bone mineral density (WBBMD) were measured using dual-energy X-ray absorptiometry. Boys showed significant (P < 0.05) positive relationships between intact osteocalcin at baseline and WBBMC at follow-up (β = 0.24), between tartrate-resistant acid phosphatase isoenzyme 5b (TRAP5b) and WBBMC (β = 0.34), and between TRAP5b and WBBMD (β = 0.34), after adjusting for potential confounding factors. In girls, adjusted means of 3-year gain in both WBBMC and WBBMD significantly increased from the lowest to highest quartiles of type 1 collagen cross-linked C-terminal telopeptide. In boys, adjusted means of 3-year gain in both WBBMC and WBBMD significantly increased from the lowest to highest quartiles of TRAP5b. Children with a high concentration of bone turnover markers tended to exhibit substantial accrual of bone minerals. These results suggest that serum levels of circulating biomarkers at age 11 predict subsequent bone mineral accrual.

Serum markers of bone turnover are increased by modest weight loss with or without weight-bearing exercise in overweight premenopausal women.

PubMed

Rector, R Scott; Loethen, Joanne; Ruebel, Meghan; Thomas, Tom R; Hinton, Pamela S

2009-10-01

Weight loss improves metabolic fitness and reduces morbidity and mortality; however, weight reduction also reduces bone mineral density (BMD) and increases bone turnover. Weight-bearing aerobic exercise may preserve bone mass and maintain normal bone turnover during weight reduction. We investigated the impact of weight-bearing and nonweight-bearing exercise on serum markers of bone formation and breakdown during short-term, modest weight loss in overweight premenopausal women. Subjects (n = 36) were assigned to 1 of 3 weight-loss interventions designed to produce a 5% reduction in body weight over 6 weeks: (i) energy restriction only (n = 11; DIET); (ii) energy restriction plus nonweight-bearing exercise (n = 12, CYCLE); or (iii) energy restriction plus weight-bearing exercise (n = 13, RUN). Bone turnover markers were measured in serum collected at baseline and after weight loss. All groups achieved a ~5% reduction in body weight (DIET = 5.2%; CYCLE = 5.0%; RUN = 4.7%). Osteocalcin (OC) and C-terminal telopeptide of type I collagen (CTX) increased with weight loss in all 3 groups (p < 0.05), whereas bone alkaline phosphatase was unaltered by the weight-loss interventions. At baseline, OC and CTX were positively correlated (r = 0.36, p = 0.03), but the strength of this association was diminished (r = 0.30, p = 0.06) after weight loss. Modest weight loss, regardless of method, resulted in a significant increase in both OC and CTX. Low-impact, weight-bearing exercise had no effect on serum markers of bone formation or resorption in premenopausal women during weight loss. Future studies that examine the effects of high-impact, weight-bearing activity on bone turnover and BMD during weight loss are warranted.

A high-density genetic map and QTL analysis of agronomic traits in foxtail millet [Setaria italica (L.) P. Beauv.] using RAD-seq.

PubMed

Wang, Jun; Wang, Zhilan; Du, Xiaofen; Yang, Huiqing; Han, Fang; Han, Yuanhuai; Yuan, Feng; Zhang, Linyi; Peng, Shuzhong; Guo, Erhu

2017-01-01

Foxtail millet (Setaria italica), a very important grain crop in China, has become a new model plant for cereal crops and biofuel grasses. Although its reference genome sequence was released recently, quantitative trait loci (QTLs) controlling complex agronomic traits remains limited. The development of massively parallel genotyping methods and next-generation sequencing technologies provides an excellent opportunity for developing single-nucleotide polymorphisms (SNPs) for linkage map construction and QTL analysis of complex quantitative traits. In this study, a high-throughput and cost-effective RAD-seq approach was employed to generate a high-density genetic map for foxtail millet. A total of 2,668,587 SNP loci were detected according to the reference genome sequence; meanwhile, 9,968 SNP markers were used to genotype 124 F2 progenies derived from the cross between Hongmiaozhangu and Changnong35; a high-density genetic map spanning 1648.8 cM, with an average distance of 0.17 cM between adjacent markers was constructed; 11 major QTLs for eight agronomic traits were identified; five co-dominant DNA markers were developed. These findings will be of value for the identification of candidate genes and marker-assisted selection in foxtail millet.

A high-density genetic map and QTL analysis of agronomic traits in foxtail millet [Setaria italica (L.) P. Beauv.] using RAD-seq

PubMed Central

Wang, Zhilan; Du, Xiaofen; Yang, Huiqing; Han, Fang; Han, Yuanhuai; Yuan, Feng; Zhang, Linyi; Peng, Shuzhong; Guo, Erhu

2017-01-01

Foxtail millet (Setaria italica), a very important grain crop in China, has become a new model plant for cereal crops and biofuel grasses. Although its reference genome sequence was released recently, quantitative trait loci (QTLs) controlling complex agronomic traits remains limited. The development of massively parallel genotyping methods and next-generation sequencing technologies provides an excellent opportunity for developing single-nucleotide polymorphisms (SNPs) for linkage map construction and QTL analysis of complex quantitative traits. In this study, a high-throughput and cost-effective RAD-seq approach was employed to generate a high-density genetic map for foxtail millet. A total of 2,668,587 SNP loci were detected according to the reference genome sequence; meanwhile, 9,968 SNP markers were used to genotype 124 F2 progenies derived from the cross between Hongmiaozhangu and Changnong35; a high-density genetic map spanning 1648.8 cM, with an average distance of 0.17 cM between adjacent markers was constructed; 11 major QTLs for eight agronomic traits were identified; five co-dominant DNA markers were developed. These findings will be of value for the identification of candidate genes and marker-assisted selection in foxtail millet. PMID:28644843

Prevalence and treatment of atherogenic dyslipidemia in the primary prevention of cardiovascular disease in Europe: EURIKA, a cross-sectional observational study.

PubMed

Halcox, Julian P; Banegas, José R; Roy, Carine; Dallongeville, Jean; De Backer, Guy; Guallar, Eliseo; Perk, Joep; Hajage, David; Henriksson, Karin M; Borghi, Claudio

2017-06-17

Atherogenic dyslipidemia is associated with poor cardiovascular outcomes, yet markers of this condition are often ignored in clinical practice. Here, we address a clear evidence gap by assessing the prevalence and treatment of two markers of atherogenic dyslipidemia: elevated triglyceride levels and low levels of high-density lipoprotein cholesterol. This cross-sectional observational study assessed the prevalence of two atherogenic dyslipidemia markers, high triglyceride levels and low high-density lipoprotein cholesterol levels, in the study population from the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (EURIKA; N = 7641; of whom 51.6% were female and 95.6% were White/Caucasian). The EURIKA population included European patients, aged at least 50 years with at least one cardiovascular risk factor but no history of cardiovascular disease. Over 20% of patients from the EURIKA population have either triglyceride or high-density lipoprotein cholesterol levels characteristic of atherogenic dyslipidemia. Furthermore, the proportions of patients with one of these markers were higher in subpopulations with type 2 diabetes mellitus or those already calculated to be at high risk of cardiovascular disease. Approximately 55% of the EURIKA population who have markers of atherogenic dyslipidemia are not receiving lipid-lowering therapy. A considerable proportion of patients with at least one major cardiovascular risk factor in the primary cardiovascular disease prevention setting have markers of atherogenic dyslipidemia. The majority of these patients are not receiving optimal treatment, as specified in international guidelines, and thus their risk of developing cardiovascular disease is possibly underestimated. The present study is registered with ClinicalTrials.gov (ID: NCT00882336).

Construction of a high-density genetic map and lint percentage and cottonseed nutrient trait QTL identification in upland cotton (Gossypium hirsutum L.).

PubMed

Liu, Dexin; Liu, Fang; Shan, Xiaoru; Zhang, Jian; Tang, Shiyi; Fang, Xiaomei; Liu, Xueying; Wang, Wenwen; Tan, Zhaoyun; Teng, Zhonghua; Zhang, Zhengsheng; Liu, Dajun

2015-10-01

Upland cotton plays a critical role not only in the textile industry, but also in the production of important secondary metabolites, such as oil and proteins. Construction of a high-density linkage map and identifying yield and seed trait quantitative trail loci (QTL) are prerequisites for molecular marker-assisted selective breeding projects. Here, we update a high-density upland cotton genetic map from recombinant inbred lines. A total of 25,313 SSR primer pairs were screened for polymorphism between Yumian 1 and T586, and 1712 SSR primer pairs were used to genotype the mapping population and construct a map. An additional 1166 loci have been added to our previously published map with 509 SSR markers. The updated genetic map spans a total recombinant length of 3338.2 cM and contains 1675 SSR loci and nine morphological markers, with an average interval of 1.98 cM between adjacent markers. Green lint (Lg) mapped on chromosome 15 in a previous report is mapped in an interval of 2.6 cM on chromosome 21. Based on the map and phenotypic data from multiple environments, 79 lint percentage and seed nutrient trait QTL are detected. These include 8 lint percentage, 13 crude protein, 15 crude oil, 8 linoleic, 10 oleic, 13 palmitic, and 12 stearic acid content QTL. They explain 3.5-62.7 % of the phenotypic variation observed. Four morphological markers identified have a major impact on lint percentage and cottonseed nutrients traits. In this study, our genetic map provides new sights into the tetraploid cotton genome. Furthermore, the stable QTL and morphological markers could be used for fine-mapping and map-based cloning.

The cross-sectional associations between objectively measured sedentary time and cardiometabolic health markers in adults - a systematic review with meta-analysis component.

PubMed

Powell, C; Herring, M P; Dowd, K P; Donnelly, A E; Carson, B P

2018-03-01

Sedentary time is viewed as an independent risk factor for adverse cardiometabolic health (CMH). No systematic review and meta-analysis on the cross-sectional associations between objectively measured sedentary time and CMH markers has been conducted. PubMed, Scopus and Web of Science Core Collection were searched for papers that examined the cross-sectional association between objectively measured sedentary time and CMH markers in adults. Forty-six papers met the inclusion criteria. The included papers had a combined sample size of 70,576 and an age range of 18-87 years. To examine the effect of increased levels of sedentary time on CMH markers, data on effect sizes and moderators were extracted, where possible. By pooling the unadjusted data from the included papers, increased sedentary time was shown to have a significant detrimental association with fasting glucose (Δ = 0.12, 95% confidence interval [CI]: 0.02, 0.23), fasting insulin (Δ = 0.19, 95% CI: 0.06, 0.32), triglycerides (Δ = 0.25, 95% CI: 0.14, 0.37), high-density lipoprotein cholesterol (Δ = -0.20, 95% CI: -0.28, -0.13) and waist circumference (Δ = 0.25, 95% CI: 0.15, 0.35). How sedentary time was quantified and the device used to measure sedentary time significantly influence the size of the effect reported. Future interventions focused on both decreasing sedentary time and increasing physical activity may be the most effective strategy to improve CMH. © 2017 World Obesity Federation.

Potential and limits to unravel the genetic architecture and predict the variation of Fusarium head blight resistance in European winter wheat (Triticum aestivum L.).

PubMed

Jiang, Y; Zhao, Y; Rodemann, B; Plieske, J; Kollers, S; Korzun, V; Ebmeyer, E; Argillier, O; Hinze, M; Ling, J; Röder, M S; Ganal, M W; Mette, M F; Reif, J C

2015-03-01

Genome-wide mapping approaches in diverse populations are powerful tools to unravel the genetic architecture of complex traits. The main goals of our study were to investigate the potential and limits to unravel the genetic architecture and to identify the factors determining the accuracy of prediction of the genotypic variation of Fusarium head blight (FHB) resistance in wheat (Triticum aestivum L.) based on data collected with a diverse panel of 372 European varieties. The wheat lines were phenotyped in multi-location field trials for FHB resistance and genotyped with 782 simple sequence repeat (SSR) markers, and 9k and 90k single-nucleotide polymorphism (SNP) arrays. We applied genome-wide association mapping in combination with fivefold cross-validations and observed surprisingly high accuracies of prediction for marker-assisted selection based on the detected quantitative trait loci (QTLs). Using a random sample of markers not selected for marker-trait associations revealed only a slight decrease in prediction accuracy compared with marker-based selection exploiting the QTL information. The same picture was confirmed in a simulation study, suggesting that relatedness is a main driver of the accuracy of prediction in marker-assisted selection of FHB resistance. When the accuracy of prediction of three genomic selection models was contrasted for the three marker data sets, no significant differences in accuracies among marker platforms and genomic selection models were observed. Marker density impacted the accuracy of prediction only marginally. Consequently, genomic selection of FHB resistance can be implemented most cost-efficiently based on low- to medium-density SNP arrays.

Aging in Rats Differentially Affects Markers of Transcriptional and Translational Capacity in Soleus and Plantaris Muscle

PubMed Central

Mobley, Christopher B.; Mumford, Petey W.; Kephart, Wesley C.; Haun, Cody T.; Holland, Angelia M.; Beck, Darren T.; Martin, Jeffrey S.; Young, Kaelin C.; Anderson, Richard G.; Patel, Romil K.; Langston, Gillis L.; Lowery, Ryan P.; Wilson, Jacob M.; Roberts, Michael D.

2017-01-01

Alterations in transcriptional and translational mechanisms occur during skeletal muscle aging and such changes may contribute to age-related atrophy. Herein, we examined markers related to global transcriptional output (i.e., myonuclear number, total mRNA and RNA pol II levels), translational efficiency [i.e., eukaryotic initiation and elongation factor levels and muscle protein synthesis (MPS) levels] and translational capacity (ribosome density) in the slow-twitch soleus and fast-twitch plantaris muscles of male Fischer 344 rats aged 3, 6, 12, 18, and 24 months (n = 9–10 per group). We also examined alterations in markers of proteolysis and oxidative stress in these muscles (i.e., 20S proteasome activity, poly-ubiquinated protein levels and 4-HNE levels). Notable plantaris muscle observations included: (a) fiber cross sectional area (CSA) was 59% (p < 0.05) and 48% (p < 0.05) greater in 12 month vs. 3 month and 24 month rats, respectively, suggesting a peak lifetime value near 12 months and age-related atrophy by 24 months, (b) MPS levels were greatest in 18 month rats (p < 0.05) despite the onset of atrophy, (c) while regulators of ribosome biogenesis [c-Myc and upstream binding factor (UBF) protein levels] generally increased with age, ribosome density linearly decreased from 3 months of age and RNA polymerase (Pol) I protein levels were lowest in 24 month rats, and d) 20S proteasome activity was robustly up-regulated in 6 and 24 month rats (p < 0.05). Notable soleus muscle observations included: (a) fiber CSA was greatest in 6 month rats and was maintained in older age groups, and (b) 20S proteasome activity was modestly but significantly greater in 24 month vs. 3/12/18 month rats (p < 0.05), and (c) total mRNA levels (suggestive of transcriptional output) trended downward in older rats despite non-significant between-group differences in myonuclear number and/or RNA Pol II protein levels. Collectively, these findings suggest that plantaris, not soleus, atrophy occurs following 12 months of age in male Fisher rats and this may be due to translational deficits (i.e., changes in MPS and ribosome density) and/or increases in proteolysis rather than increased oxidative stress and/or alterations in global transcriptional mechanisms. PMID:28775694

Cardiovascular disease parameters in periodontitis.

PubMed

Monteiro, Andréa M; Jardini, Maria A N; Alves, Sarah; Giampaoli, Viviana; Aubin, Elisete C Q; Figueiredo Neto, Antônio M; Gidlund, Magnus

2009-03-01

Recently, there has been an increasing in the impact of oral health on atherosclerosis and subsequent cardiovascular disease. The aim of this study is to investigate the association between chronic periodontitis and cardiovascular risk markers. Forty patients with periodontitis and 40 healthy gender-, body mass index-, and age-matched individuals were compared by measuring total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, levels of cytokines, antibodies against oxidized low-density lipoprotein, thiobarbituric acid reactive substances, total and differential white blood cell counts, and the non-linear index of refraction. The levels of triglycerides and high-density lipoprotein in periodontitis patients were significantly higher and lower, respectively (P = 0.002 and P = 0.0126), compared to controls. Total cholesterol, low-density lipoprotein, and lipid peroxide levels were the same in both groups (P = 0.2943, P = 0.1284, and P = 0.067, respectively). Interleukin (IL)-6 and -8, antibodies against oxidized low-density lipoprotein, and leukocyte and neutrophil counts were significantly higher in periodontitis patients (P <0.05). The value of the non-linear index of refraction of low-density lipoprotein solutions was higher in the controls (P = 0.015) compared to individuals with periodontitis. Our results confirmed and further strengthened the suggested association between coronary artery disease and periodontitis.

Lipoprotein Changes in HIV-Infected Antiretroviral-Naïve Individuals after Starting Antiretroviral Therapy: ACTG Study A5152s Stein: Lipoprotein Changes on Antiretroviral Therapy

PubMed Central

Stein, James H.; Komarow, Lauren; Cotter, Bruno R.; Currier, Judith S.; Dubé, Michael P.; Fichtenbaum, Carl J.; Gerschenson, Mariana; Mitchell, Carol K.C.; Murphy, Robert L.; Squires, Kathleen; Parker, Robert A.; Torriani, Francesca J.

2008-01-01

Background Dyslipidemia is a frequent complication of antiretroviral therapy (ART) for patients with human immunodeficiency virus infection (HIV). The effects of ART on lipoproteins are less well-understood, and have not been investigated in a prospective study where assignment to ART is randomized. Objective To evaluate the effects of three class-sparing ART regimens on lipids and lipoproteins. Methods This was a substudy of a prospective, multicenter study treatment-naïve HIV-infected individuals randomly assigned to receive a regimen of nucleoside reverse transcriptase inhibitors (NRTIs) + the non-nucleoside reverse transcriptase inhibitor efavirenz, NRTIs + the protease inhibitor lopinavir/ritonavir, or a NRTI-sparing regimen of efavirenz + lopinavir/ritonavir. Lipoproteins were measured by nuclear magnetic resonance spectroscopy. Results Among the 82 participants, total and small low-density lipoprotein concentrations increased (median, interquartile range) by 152 (-49 - +407, p<0.01) and 130 (-98 - +417, p<0.01) nmol/L, respectively, especially in the arms containing lopinavir/ritonavir (pKW<0.04). Very low-density lipoproteins also increased (p<0.01), with a larger increase in the arms that contained lopinavir/ritonavir (p=0.022). High-density lipoproteins increased by 6.0 nmol/L (2.8 - 10.4, p<0.01), but differences between arms were not significant (pKW=0.069). Changes were not related to changes in markers of insulin/glucose metabolism. Conclusions Total and small low-density lipoprotein concentrations increased, especially in the arms containing lopinavir/ritonavir, as did increases in total very low-density lipoproteins. Adverse changes were especially prominent in the arm with efavirenz + lopinavir/ritonavir. PMID:19956354

The clinical utility of bone marker measurements in osteoporosis

PubMed Central

2013-01-01

Osteoporosis is characterised by low bone mass and structural deterioration of bone tissue, resulting in increased fragility and susceptibility to fracture. Osteoporotic fractures are a significant cause of morbidity and mortality. Direct medical costs from such fractures in the UK are currently estimated at over two billion pounds per year, resulting in a substantial healthcare burden that is expected to rise exponentially due to increasing life expectancy. Currently bone mineral density is the WHO standard for diagnosis of osteoporosis, but poor sensitivity means that potential fractures will be missed if it is used alone. During the past decade considerable progress has been made in the identification and characterisation of specific biomarkers to aid the management of metabolic bone disease. Technological developments have greatly enhanced assay performance producing reliable, rapid, non-invasive cost effective assays with improved sensitivity and specificity. We now have a greater understanding of the need to regulate pre-analytical sample collection to minimise the effects of biological variation. However, bone turnover markers (BTMs) still have limited clinical utility. It is not routinely recommended to use BTMs to select those at risk of fractures, but baseline measurements of resorption markers are useful before commencement of anti-resorptive treatment and can be checked 3–6 months later to monitor response and adherence to treatment. Similarly, formation markers can be used to monitor bone forming agents. BTMs may also be useful when monitoring patients during treatment holidays and aid in the decision as to when therapy should be recommenced. Recent recommendations by the Bone Marker Standards Working Group propose to standardise research and include a specific marker of bone resorption (CTX) and bone formation (P1NP) in all future studies. It is hoped that improved research in turn will lead to optimised markers for the clinical management of osteoporosis and other bone diseases. PMID:23984630

Bone health in cerebral palsy and introduction of a novel therapy

PubMed Central

Scheinberg, Morton Aaron; Golmia, Ricardo Prado; Sallum, Adriana Maluf Elias; Pippa, Maria Guadalupe Barbosa; Cortada, Aline Pinheiros dos Santos; da Silva, Telma Gomes

2015-01-01

ABSTRACT Objective To assess the bone health status of children with cerebral palsy and the therapeutic effect of denosumab in a subgroup of children with cerebral palsy and decreased bone mass. Methods Children with cerebral palsy were evaluated according to their motor disability score (classification system gross motor functions III to V), bone density and bone turnover markers. Dual X-ray energy absorption was used to measure the lumbar spine, and total body, except the head. Thereafter a group of children with cerebral palsy and osteoporosis was treated with denosumab, a fully human monoclonal antibody. Bone turnover markers were measured before and three months after treatment. Results Reduction in bone mineral density was observed, particularly in children with greater impairment evaluated by the motor score. Decreased bone turnover markers were found in a selected group of children three months after exposure to denosumab. Conclusion Bone loss was present in children with significant impairment of motor function, as well as decreased serum levels of bone resorption markers with new forms. PMID:26761553

Developmental trajectories of EEG sleep slow wave activity as a marker for motor skill development during adolescence: a pilot study.

PubMed

Lustenberger, Caroline; Mouthon, Anne-Laure; Tesler, Noemi; Kurth, Salome; Ringli, Maya; Buchmann, Andreas; Jenni, Oskar G; Huber, Reto

2017-01-01

Reliable markers for brain maturation are important to identify neural deviations that eventually predict the development of mental illnesses. Recent studies have proposed topographical EEG-derived slow wave activity (SWA) during NREM sleep as a mirror of cortical development. However, studies about the longitudinal stability as well as the relationship with behavioral skills are needed before SWA topography may be considered such a reliable marker. We examined six subjects longitudinally (over 5.1 years) using high-density EEG and a visuomotor learning task. All subjects showed a steady increase of SWA at a frontal electrode and a decrease in central electrodes. Despite these large changes in EEG power, SWA topography was relatively stable within each subject during development indicating individual trait-like characteristics. Moreover, the SWA changes in the central cluster were related to the development of specific visuomotor skills. Taken together with the previous work in this domain, our results suggest that EEG sleep SWA represents a marker for motor skill development and further supports the idea that SWA mirrors cortical development during childhood and adolescence. © 2016 Wiley Periodicals, Inc.

Dermal Stem Cells Can Differentiate Down an Endothelial Lineage

PubMed Central

Bell, Emma; Richardson, Gavin D.; Jahoda, Colin A.; Gledhill, Karl; Phillips, Helen M.; Henderson, Deborah; Owens, W. Andrew

2012-01-01

In this study, we have demonstrated that cells of neural crest origin located in the dermal papilla (DP) exhibit endothelial marker expression and a functional activity. When grown in endothelial growth media, DP primary cultures upregulate expression of vascular endothelial growth factor receptor 1 (FLT1) mRNA and downregulate expression of the dermal stem cell marker α-smooth muscle actin. DP cells have demonstrated functional characteristics of endothelial cells, including the ability to form capillary-like structures on Matrigel, increase uptake of low-density lipoprotein and upregulate ICAM1 (CD54) in response to tumour necrosis factor alpha (TNF-α) stimulation. We confirmed that these observations were not due to contaminating endothelial cells, by using DP clones. We have also used the WNT1cre/ROSA26R and WNT1cre/YFP lineage-tracing mouse models to identify a population of neural crest-derived cells in DP cultures that express the endothelial marker PECAM (CD31); these cells also form capillary-like structures on Matrigel. Importantly, cells of neural crest origin that express markers of endothelial and mesenchymal lineages exist within the dermal sheath of the vibrissae follicle. PMID:22571645

The muscle contraction mode determines lymphangiogenesis differentially in rat skeletal and cardiac muscles by modifying local lymphatic extracellular matrix microenvironments.

PubMed

Greiwe, L; Vinck, M; Suhr, F

2016-05-01

Lymphatic vessels are of special importance for tissue homeostasis, and increases of their density may foster tissue regeneration. Exercise could be a relevant tool to increase lymphatic vessel density (LVD); however, a significant lack of knowledge remains to understand lymphangiogenesis in skeletal muscles upon training. Interestingly, training-induced lymphangiogenesis has never been studied in the heart. We studied lymphangiogenesis and LVD upon chronic concentric and chronic eccentric muscle contractions in both rat skeletal (Mm. Edl and Sol) and cardiac muscles. We found that LVD decreased in both skeletal muscles specifically upon eccentric training, while this contraction increased LVD in cardiac tissue. These observations were supported by opposing local remodelling of lymphatic vessel-specific extracellular matrix components in skeletal and cardiac muscles and protein levels of lymphatic markers (Lyve-1, Pdpn, Vegf-C/D). Confocal microscopy further revealed transformations of lymphatic vessels into vessels expressing both blood (Cav-1) and lymphatic (Vegfr-3) markers upon eccentric training specifically in skeletal muscles. In addition and phenotype supportive, we found increased inflammation (NF-κB/p65, Il-1β, Ifn-γ, Tnf-α and MPO(+) cells) in eccentrically stressed skeletal, but decreased levels in cardiac muscles. Our data provide novel mechanistic insights into lymphangiogenic processes in skeletal and cardiac muscles upon chronic muscle contraction modes and demonstrate that both tissues adapt in opposing manners specifically to eccentric training. These data are highly relevant for clinical applications, because eccentric training serves as a sufficient strategy to increase LVD and to decrease inflammation in cardiac tissue, for example in order to reduce tissue abortion in transplantation settings. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

The Effects of Creatine Monohydrate on Permeability of Coronary Artery Endothelium and Level of Blood Lipoprotein in Diabetic Rats.

PubMed

Rahmani, Asghar; Asadollahi, Khairollah; Soleimannejad, Kourosh; Khalighi, Zahra; Mohsenzadeh, Yosouf; Hemati, Ruhollah; Moradkhani, Atefeh; Abangah, Ghobad

2016-09-01

Creatine monohydrate has beneficial effects on serum glucose. This study aimed to investigate the effects of creatine on serum biochemical markers and permeability of coronary arteries among diabetic rats. 32 Wistar rats, which weighed 150-200 grams were randomly divided into 4 groups including: group I, control; group II, creatine monohydrate; group III, diabetic rats; and group IV, diabetic rats + creatine. Creatine monohydrate was applied by 400 mg/kg/daily for 5 months. Animals' weights and blood samples were taken before and after the study. Endothelial permeability rate was measured by Evans Blue method. Data were analysed by SPSS 16. At the end of fifth month, rats' weights in diabetic group under treatment with creatine, compared to those without, increased significantly (p<0.0001). Also, the serum levels of triglyceride (TG), cholesterol, glucose and low density lipoprotein (LDL)- cholesterol decreased significantly among those under treatment with creatine (p<0.05), but high density lipoprotein (HDL)- cholesterol increased significantly (p<0.002). Permeability rate of coronary arteries was reduced significantly in the diabetic group treated by creatine compared to untreated groups, closed to the intact group (p<0.001). Results of this study showed that creatine monohydrate caused an improvement of serum biochemical markers associated with diabetes and reduced the permeability rate of coronary arteries among diabetic rats. © 2016 by the Association of Clinical Scientists, Inc.

Dietary Supplementation with Virgin Coconut Oil Improves Lipid Profile and Hepatic Antioxidant Status and Has Potential Benefits on Cardiovascular Risk Indices in Normal Rats.

PubMed

Famurewa, Ademola C; Ekeleme-Egedigwe, Chima A; Nwali, Sophia C; Agbo, Ngozi N; Obi, Joy N; Ezechukwu, Goodness C

2018-05-04

Research findings that suggest beneficial health effects of dietary supplementation with virgin coconut oil (VCO) are limited in the published literature. This study investigated the in vivo effects of a 5-week VCO-supplemented diet on lipid profile, hepatic antioxidant status, hepatorenal function, and cardiovascular risk indices in normal rats. Rats were randomly divided into 3 groups: 1 control and 2 treatment groups (10% and 15% VCO-supplemented diets) for 5 weeks. Serum and homogenate samples were used to analyze lipid profile, hepatorenal function markers, hepatic activities of antioxidant enzymes, and malondialdehyde level. Lipid profile of animals fed VCO diets showed significant reduction in total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels; high-density lipoprotein (HDL) level increased significantly (p < .05) compared to control; and there were beneficial effects on cardiovascular risk indices. The level of malondialdehyde (MDA), a lipid peroxidation marker, remarkably reduced and activities of hepatic antioxidant enzymes-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)-were markedly increased in VCO diet-fed rats. The VCO diet significantly modulated creatinine, sodium (Na + ), potassium (K + ), chloride (Cl - ), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) compared to control. The findings suggest a beneficial effect of VCO on lipid profile, renal status, hepatic antioxidant defense system, and cardiovascular risk indices in rats.

Assessing tumor vascularization as a potential biomarker of imatinib resistance in gastrointestinal stromal tumors by dynamic contrast-enhanced magnetic resonance imaging.

PubMed

Consolino, Lorena; Longo, Dario Livio; Sciortino, Marianna; Dastrù, Walter; Cabodi, Sara; Giovenzana, Giovanni Battista; Aime, Silvio

2017-07-01

Most metastatic gastrointestinal stromal tumors (GISTs) develop resistance to the first-line imatinib treatment. Recently, increased vessel density and angiogenic markers were reported in GISTs with a poor prognosis, suggesting that angiogenesis is implicated in GIST tumor progression and resistance. The purpose of this study was to investigate the relationship between tumor vasculature and imatinib resistance in different GIST mouse models using a noninvasive magnetic resonance imaging (MRI) functional approach. Immunodeficient mice (n = 8 for each cell line) were grafted with imatinib-sensitive (GIST882 and GIST-T1) and imatinib-resistant (GIST430) human cell lines. Dynamic contrast-enhanced MRI (DCE-MRI) was performed on GIST xenografts to quantify tumor vessel permeability (K trans ) and vascular volume fraction (v p ). Microvessel density (MVD), permeability (mean dextran density, MDD), and angiogenic markers were evaluated by immunofluorescence and western blot assays. Dynamic contrast-enhanced magnetic resonance imaging showed significantly increased vessel density (P < 0.0001) and permeability (P = 0.0002) in imatinib-resistant tumors compared to imatinib-sensitive ones. Strong positive correlations were observed between MRI estimates, K trans and v p , and their related ex vivo values, MVD (r = 0.78 for K trans and r = 0.82 for v p ) and MDD (r = 0.77 for K trans and r = 0.94 for v p ). In addition, higher expression of vascular endothelial growth factor receptors (VEGFR2 and VEFGR3) was seen in GIST430. Dynamic contrast-enhanced magnetic resonance imaging highlighted marked differences in tumor vasculature and microenvironment properties between imatinib-resistant and imatinib-sensitive GISTs, as also confirmed by ex vivo assays. These results provide new insights into the role that DCE-MRI could play in GIST characterization and response to GIST treatment. Validation studies are needed to confirm these findings.

Sublingual testosterone replacement improves muscle mass and strength, decreases bone resorption, and increases bone formation markers in hypogonadal men--a clinical research center study.

PubMed

Wang, C; Eyre, D R; Clark, R; Kleinberg, D; Newman, C; Iranmanesh, A; Veldhuis, J; Dudley, R E; Berman, N; Davidson, T; Barstow, T J; Sinow, R; Alexander, G; Swerdloff, R S

1996-10-01

To study the effects of androgen replacement therapy on muscle mass and strength and bone turnover markers in hypogonadal men, we administered sublingual testosterone (T) cyclodextrin (SLT; 5 mg, three times daily) to 67 hypogonadal men (baseline serum T, < 8.4 nmol/L) recruited from 4 centers in the U.S.: Torrance (n = 34), Durham (n = 12), New York (n = 9), and Salem (n = 12). Subjects who had received prior T therapy were withdrawn from injections for at least 6 weeks and from oral therapy for 4 weeks. Body composition, muscle strength, and serum and urinary bone turnover markers were measured before and after 6 months of SLT. We have shown previously that this regimen for 60 days will maintain adequate serum T levels and restore sexual function. Total body (P = 0.0104) and lean body mass (P = 0.007) increased with SLT treatment in the 34 subjects in whom body composition was assessed. There was no significant change in total body fat or percent fat. The increase in lean body mass was mainly in the legs; the right leg lean mass increased from 8.9 +/- 0.3 kg at 0 months to 9.2 +/- 0.3 kg at 6 months (P = 0.0008). This increase in leg lean mass was associated with increased leg muscle strength, assessed by leg press (0 months, 139.0 +/- 4.0 kg; 6 months, 147.7 +/- 4.2 kg; P = 0.0038). SLT replacement in hypogonadal men led to small, but significant, decreases in serum Ca (P = 0.0029) and the urinary calcium/creatinine ratio (P = 0.0066), which were associated with increases in serum PTH (P = 0.0001). At baseline, the urinary type I collagen-cross linked N-telopeptides/creatinine ratio [75.6 +/- 7.9 nmol bone collagen equivalents (BCE/mmol] was twice the normal adult male mean (41.0 +/- 3.6 nmol BCE/mmol) and was significantly decreased in response to SLT treatment at 6 months (68.2 +/- 7.7 nmol BCE/mmol; P = 0.0304) without significant changes in urinary creatinine. Serum skeletal alkaline phosphatase did not change. In addition, SLT replacement caused significant increases in serum osteocalcin (P = 0.0001) and type I procollagen (P = 0.0012). Bone mineral density did not change during the 6 months of SLT treatment. We conclude that SLT replacement therapy resulted in increases in lean muscle mass and muscle strength. Like estrogen replacement in hypogonadal postmenopausal females, androgen replacement therapy led to decreased bone resorption and urinary calcium excretion. Moreover, androgen replacement therapy may have the additional benefit of increasing bone formation. A longer term study for several years duration would be necessary to demonstrate whether these changes in bone turnover marker levels will result in increased bone mineral density decreased fracture risks, and reduced frailty in hypogonadal men.

Calcium and vitamin D supplementation maintains parathyroid hormone and improves bone density during initial military training: a randomized, double-blind, placebo controlled trial.

PubMed

Gaffney-Stomberg, Erin; Lutz, Laura J; Rood, Jennifer C; Cable, Sonya J; Pasiakos, Stefan M; Young, Andrew J; McClung, James P

2014-11-01

Calcium and vitamin D are essential nutrients for bone health. Periods of activity with repetitive mechanical loading, such as military training, may result in increases in parathyroid hormone (PTH), a key regulator of Ca metabolism, and may be linked to the development of stress fractures. Previous studies indicate that consumption of a Ca and vitamin D supplement may reduce stress fracture risk in female military personnel during initial military training, but circulating markers of Ca and bone metabolism and measures of bone density and strength have not been determined. This randomized, double-blind, placebo-controlled trial sought to determine the effects of providing supplemental Ca and vitamin D (Ca+Vit D, 2000mg and 1000IU/d, respectively), delivered as 2 snack bars per day throughout 9weeks of Army initial military training (or basic combat training, BCT) on PTH, vitamin D status, and measures of bone density and strength in personnel undergoing BCT, as well as independent effects of BCT on bone parameters. A total of 156 men and 87 women enrolled in Army BCT (Fort Sill, OK; 34.7°N latitude) volunteered for this study. Anthropometric, biochemical, and dietary intake data were collected pre- and post-BCT. In addition, peripheral quantitative computed tomography was utilized to assess tibia bone density and strength in a subset of volunteers (n=46). Consumption of supplemental Ca+Vit D increased circulating ionized Ca (group-by-time, P=0.022), maintained PTH (group-by-time, P=0.032), and increased the osteoprotegerin:RANKL ratio (group-by-time, P=0.006). Consistent with the biochemical markers, Ca+Vit D improved vBMD (group-by-time, P=0.024) at the 4% site and cortical BMC (group-by-time, P=0.028) and thickness (group-by-time, P=0.013) at the 14% site compared to placebo. These data demonstrate the benefit of supplemental Ca and vitamin D for maintaining bone health during periods of elevated bone turnover, such as initial military training. This trial was registered with ClincialTrials.gov, NCT01617109. Published by Elsevier Inc.

A Large Maize (Zea mays L.) SNP Genotyping Array: Development and Germplasm Genotyping, and Genetic Mapping to Compare with the B73 Reference Genome

PubMed Central

Ganal, Martin W.; Durstewitz, Gregor; Polley, Andreas; Bérard, Aurélie; Buckler, Edward S.; Charcosset, Alain; Clarke, Joseph D.; Graner, Eva-Maria; Hansen, Mark; Joets, Johann; Le Paslier, Marie-Christine; McMullen, Michael D.; Montalent, Pierre; Rose, Mark; Schön, Chris-Carolin; Sun, Qi; Walter, Hildrun; Martin, Olivier C.; Falque, Matthieu

2011-01-01

SNP genotyping arrays have been useful for many applications that require a large number of molecular markers such as high-density genetic mapping, genome-wide association studies (GWAS), and genomic selection. We report the establishment of a large maize SNP array and its use for diversity analysis and high density linkage mapping. The markers, taken from more than 800,000 SNPs, were selected to be preferentially located in genes and evenly distributed across the genome. The array was tested with a set of maize germplasm including North American and European inbred lines, parent/F1 combinations, and distantly related teosinte material. A total of 49,585 markers, including 33,417 within 17,520 different genes and 16,168 outside genes, were of good quality for genotyping, with an average failure rate of 4% and rates up to 8% in specific germplasm. To demonstrate this array's use in genetic mapping and for the independent validation of the B73 sequence assembly, two intermated maize recombinant inbred line populations – IBM (B73×Mo17) and LHRF (F2×F252) – were genotyped to establish two high density linkage maps with 20,913 and 14,524 markers respectively. 172 mapped markers were absent in the current B73 assembly and their placement can be used for future improvements of the B73 reference sequence. Colinearity of the genetic and physical maps was mostly conserved with some exceptions that suggest errors in the B73 assembly. Five major regions containing non-colinearities were identified on chromosomes 2, 3, 6, 7 and 9, and are supported by both independent genetic maps. Four additional non-colinear regions were found on the LHRF map only; they may be due to a lower density of IBM markers in those regions or to true structural rearrangements between lines. Given the array's high quality, it will be a valuable resource for maize genetics and many aspects of maize breeding. PMID:22174790

Plasma membrane cholesterol level and agonist-induced internalization of δ-opioid receptors; colocalization study with intracellular membrane markers of Rab family.

PubMed

Brejchova, Jana; Vosahlikova, Miroslava; Roubalova, Lenka; Parenti, Marco; Mauri, Mario; Chernyavskiy, Oleksandr; Svoboda, Petr

2016-08-01

Decrease of cholesterol level in plasma membrane of living HEK293 cells transiently expressing FLAG-δ-OR by β-cyclodextrin (β-CDX) resulted in a slight internalization of δ-OR. Massive internalization of δ-OR induced by specific agonist DADLE was diminished in cholesterol-depleted cells. These results suggest that agonist-induced internalization of δ-OR, which has been traditionally attributed exclusively to clathrin-mediated pathway, proceeds at least partially via membrane domains. Identification of internalized pools of FLAG-δ-OR by colocalization studies with proteins of Rab family indicated the decreased presence of receptors in early endosomes (Rab5), late endosomes and lysosomes (Rab7) and fast recycling vesicles (Rab4). Slow type of recycling (Rab11) was unchanged by cholesterol depletion. As expected, agonist-induced internalization of oxytocin receptors was totally suppressed in β-CDX-treated cells. Determination of average fluorescence lifetime of TMA-DPH, the polar derivative of hydrophobic membrane probe diphenylhexatriene, in live cells by FLIM indicated a significant alteration of the overall PM structure which may be interpreted as an increased "water-accessible space" within PM area. Data obtained by studies of HEK293 cells transiently expressing FLAG-δ-OR by "antibody feeding" method were extended by analysis of the effect of cholesterol depletion on distribution of FLAG-δ-OR in sucrose density gradients prepared from HEK293 cells stably expressing FLAG-δ-OR. Major part of FLAG-δ-OR was co-localized with plasma membrane marker Na,K-ATPase and β-CDX treatment resulted in shift of PM fragments containing both FLAG-δ-OR and Na,K-ATPase to higher density. Thus, the decrease in content of the major lipid constituent of PM resulted in increased density of resulting PM fragments.

Breeding value prediction for production traits in layer chickens using pedigree or genomic relationships in a reduced animal model.

PubMed

Wolc, Anna; Stricker, Chris; Arango, Jesus; Settar, Petek; Fulton, Janet E; O'Sullivan, Neil P; Preisinger, Rudolf; Habier, David; Fernando, Rohan; Garrick, Dorian J; Lamont, Susan J; Dekkers, Jack C M

2011-01-21

Genomic selection involves breeding value estimation of selection candidates based on high-density SNP genotypes. To quantify the potential benefit of genomic selection, accuracies of estimated breeding values (EBV) obtained with different methods using pedigree or high-density SNP genotypes were evaluated and compared in a commercial layer chicken breeding line. The following traits were analyzed: egg production, egg weight, egg color, shell strength, age at sexual maturity, body weight, albumen height, and yolk weight. Predictions appropriate for early or late selection were compared. A total of 2,708 birds were genotyped for 23,356 segregating SNP, including 1,563 females with records. Phenotypes on relatives without genotypes were incorporated in the analysis (in total 13,049 production records).The data were analyzed with a Reduced Animal Model using a relationship matrix based on pedigree data or on marker genotypes and with a Bayesian method using model averaging. Using a validation set that consisted of individuals from the generation following training, these methods were compared by correlating EBV with phenotypes corrected for fixed effects, selecting the top 30 individuals based on EBV and evaluating their mean phenotype, and by regressing phenotypes on EBV. Using high-density SNP genotypes increased accuracies of EBV up to two-fold for selection at an early age and by up to 88% for selection at a later age. Accuracy increases at an early age can be mostly attributed to improved estimates of parental EBV for shell quality and egg production, while for other egg quality traits it is mostly due to improved estimates of Mendelian sampling effects. A relatively small number of markers was sufficient to explain most of the genetic variation for egg weight and body weight.

Isolation of the Lateral Border Recycling Compartment using a diaminobenzidine-induced density shift

PubMed Central

Sullivan, David P.; Rüffer, Claas; Muller, William A.

2014-01-01

The migration of leukocytes across the endothelium and into tissue is critical to mounting an inflammatory response. The Lateral Border Recycling Compartment (LBRC), a complex vesicular-tubule invagination of the plasma membrane found at endothelial cell borders, plays an important role in the this process. Although a few proteins have been shown to be present in the LBRC, no unique marker is known. Here we detail methods that can be used to characterize a subcellular compartment that lacks an identifying marker. Initial characterization of the LBRC was performed using standard subcellular fractionation with sucrose gradients and took advantage of the observation that the compartment migrated at a lower density than other membrane compartments. To isolate larger quantities of the compartment, we modified a classic technique known as a diaminobenzidine (DAB)-induced density shift. The DAB-induced density shift allowed for specific isolation of membranes labeled with HRP conjugated antibody. Because the LBRC could be differentially labeled at 4°C and 37°C, we were able to identify proteins that are enriched in the compartment, despite lacking a unique marker. These methods serve as a model to others studying poorly characterized compartments and organelles and are applicable to a wide variety of biological systems. PMID:24915828

An Ultra-High-Density, Transcript-Based, Genetic Map of Lettuce

PubMed Central

Truco, Maria José; Ashrafi, Hamid; Kozik, Alexander; van Leeuwen, Hans; Bowers, John; Wo, Sebastian Reyes Chin; Stoffel, Kevin; Xu, Huaqin; Hill, Theresa; Van Deynze, Allen; Michelmore, Richard W.

2013-01-01

We have generated an ultra-high-density genetic map for lettuce, an economically important member of the Compositae, consisting of 12,842 unigenes (13,943 markers) mapped in 3696 genetic bins distributed over nine chromosomal linkage groups. Genomic DNA was hybridized to a custom Affymetrix oligonucleotide array containing 6.4 million features representing 35,628 unigenes of Lactuca spp. Segregation of single-position polymorphisms was analyzed using 213 F7:8 recombinant inbred lines that had been generated by crossing cultivated Lactuca sativa cv. Salinas and L. serriola acc. US96UC23, the wild progenitor species of L. sativa. The high level of replication of each allele in the recombinant inbred lines was exploited to identify single-position polymorphisms that were assigned to parental haplotypes. Marker information has been made available using GBrowse to facilitate access to the map. This map has been anchored to the previously published integrated map of lettuce providing candidate genes for multiple phenotypes. The high density of markers achieved in this ultradense map allowed syntenic studies between lettuce and Vitis vinifera as well as other plant species. PMID:23550116

An Ultra-High-Density, Transcript-Based, Genetic Map of Lettuce.

PubMed

Truco, Maria José; Ashrafi, Hamid; Kozik, Alexander; van Leeuwen, Hans; Bowers, John; Wo, Sebastian Reyes Chin; Stoffel, Kevin; Xu, Huaqin; Hill, Theresa; Van Deynze, Allen; Michelmore, Richard W

2013-04-09

We have generated an ultra-high-density genetic map for lettuce, an economically important member of the Compositae, consisting of 12,842 unigenes (13,943 markers) mapped in 3696 genetic bins distributed over nine chromosomal linkage groups. Genomic DNA was hybridized to a custom Affymetrix oligonucleotide array containing 6.4 million features representing 35,628 unigenes of Lactuca spp. Segregation of single-position polymorphisms was analyzed using 213 F 7:8 recombinant inbred lines that had been generated by crossing cultivated Lactuca sativa cv. Salinas and L. serriola acc. US96UC23, the wild progenitor species of L. sativa The high level of replication of each allele in the recombinant inbred lines was exploited to identify single-position polymorphisms that were assigned to parental haplotypes. Marker information has been made available using GBrowse to facilitate access to the map. This map has been anchored to the previously published integrated map of lettuce providing candidate genes for multiple phenotypes. The high density of markers achieved in this ultradense map allowed syntenic studies between lettuce and Vitis vinifera as well as other plant species. Copyright © 2013 Truco et al.

The prognostic significance of lymphatics in colorectal liver metastases.

PubMed

Muralidharan, Vijayaragavan; Nguyen, Linh; Banting, Jonathan; Christophi, Christopher

2014-01-01

Background. Colorectal Cancer (CRC) is the most common form of cancer diagnosed in Australia across both genders. Approximately, 40%-60% of patients with CRC develop metastasis, the liver being the most common site. Almost 70% of CRC mortality can be attributed to the development of liver metastasis. This study examines the pattern and density of lymphatics in colorectal liver metastases (CLM) as predictors of survival following hepatic resection for CLM. Methods. Patient tissue samples were obtained from the Victorian Cancer Biobank. Immunohistochemistry was used to examine the spatial differences in blood and lymphatic vessel densities between different regions within the tumor (CLM) and surrounding host tissue. Lymphatic vessel density (LVD) was assessed as a potential prognostic marker. Results. Patients with low lymphatic vessel density in the tumor centre, tumor periphery, and adjacent normal liver demonstrated a significant disease-free survival advantage compared to patients with high lymphatic vessel density (P = 0.01, P > 0.01, and P = 0.05, resp.). Lymphatic vessel density in the tumor centre and periphery and adjacent normal liver was an accurate predictive marker of disease-free survival (P = 0.05). Conclusion. Lymphatic vessel density in CLM appears to be an accurate predictor of recurrence and disease-free survival.

Brain Barrier Disruption and Region-Specific Neuronal Degeneration during Necrotizing Enterocolitis in Preterm Pigs.

PubMed

Brunse, Anders; Abbaspour, Afrouz; Sangild, Per Torp

2018-06-06

Necrotizing enterocolitis (NEC) increases the risk of brain injury and impaired neurodevelopment. Rapid brain maturation prior to birth may explain why preterm brains are particularly vulnerable to serious infections. Using pigs as models, we hypothesized that preterm birth was associated with altered blood-cerebrospinal fluid (CSF) barrier (BCSFB) function and cerebral structural deficits, and that NEC was associated with systemic inflammation, BCSFB disruption, and neuroinflammation. First, cesarean-delivered preterm and term pigs (n = 43-44) were euthanized at birth to investigate BCSFB function and markers of brain structural maturation, or on day 5 to measure markers of blood-brain barrier maturation in the hippocampus and striatum (experiment 1). Next, preterm pigs (n = 162) were fed increasing volumes of infant formula to assess NEC lesions, systemic inflammation, BCSFB permeability, cerebral histopathology, hippocampal micro-glial density, and cytokine levels on day 5 (experiments 2 and 3). In experiment 1, preterm newborns had increased CSF-plasma ratios of albumin and raffinose, reduced CSF glucose levels, as well as increased cerebral hydration and reduced white matter myelination compared with term animals. We observed lower hippocampal (but not striatal) perivascular astrocyte coverage for the first 5 days after preterm birth, accompanied by altered cell junction protein levels. In experiments 2 and- 3, piglets with severe NEC lesions showed reduced blood thrombocytes and increased plasma C-reactive protein and interleukin-6 levels. NEC was associated with increased CSF-plasma albumin and raffinose ratios, reduced CSF leukocyte numbers, and increased cerebral hydration. In the hippocampus, NEC was associated with pyramidal neuron loss and increased interleukin-6 levels. In the short term, NEC did not affect cerebral myelination or microglia density. In conclusion, altered BCSFB properties and brain structural deficits were observed in pigs after preterm birth. Acute gastrointestinal NEC lesions were associated with systemic inflammation, increased BCSFB permeability and region-specific neuronal damage. The results demonstrate the importance of early interventions against NEC to prevent brain injury in preterm infants. © 2018 S. Karger AG, Basel.

The association between high plasma homocysteine levels and lower bone mineral density in Slovak women: the impact of vegetarian diet.

PubMed

Krivosíková, Zora; Krajcovicová-Kudlácková, Marica; Spustová, Viera; Stefíková, Kornélia; Valachovicová, Martina; Blazícek, Pavel; Nĕmcová, Tatiana

2010-04-01

A long-term vegetarian diet is generally poor in vitamin B group. The lack of vitamin B(12) together with vitamin B(6) and folate deficiency is closely related to homocysteine metabolism. Hyperhomocysteinemia was found to be associated with increased bone turnover markers and increased fracture risk. Thus, hyperhomocysteinemia, vitamin B(12) and folate deficiency may be regarded as novel risk factors for micronutrient deficiency-related osteoporosis. To assess the possible impact of a vegetarian diet on bone mineral density in cohort of Slovak vegetarian women. Fasting serum glucose, albumin, calcium, phosphorous and creatinine as well as bone markers, serum vitamin B(12), folate and plasma levels of total homocysteine were assessed in two nutritional groups (vegetarians vs. nonvegetarians) of apparently healthy women (age range 20-70 years). Bone mineral density of the femoral neck, trochanter, total femur and lumbar spine was measured in all subjects. Vegetarians had a significantly lower weight (p < 0.05), higher PTH (p < 0.01) and homocysteine (p < 0.001). Vitamin B(12) was significantly higher in nonvegetarians (p < 0.001). No differences were observed in folate levels. Univariate analysis showed significant association between homocysteine and B(12) (p < 0.01), folate (p < 0.001), creatinine (p < 0.001), total proteins (p < 0.049), age (p < 0.001) and vegetarian food intake (p < 0.001). Vegetarians had a significantly lower TrFBMD (p < 0.05) and ToFBMD (p < 0.05). Age and CTx were significant predictors in all sites of measured BMD and PTH. A strong correlation between homocysteine and FNBMD (r = -0.2009, p < 0.002), TrFBMD (r = -0.1810, p < 0.004) and ToFBMD (r = -0.2225, p < 0.001) was found in all subjects. Homocysteine is one of the predictors of bone mineral density, and hyperhomocysteinemia is associated with lower bone mineral density. In healthy adults, homocysteine levels are dependent on age as well as on nutritional habits. Thus, elderly women on a vegetarian diet seem to be at higher risk of osteoporosis development than nonvegetarian women.

The fine-scale genetic structure of the two-spotted spider mite in a commercial greenhouse.

PubMed

Uesugi, R; Kunimoto, Y; Osakabe, Mh

2009-02-01

The fine-scale genetic structure of Tetranychus urticae Koch was studied to estimate local gene flow within a rose tree habitat in a commercial greenhouse using seven microsatellite markers. Two beds of rose trees with different population densities were selected and 18 consecutive quadrats of 1.2 m length were sequentially established in each bed. Heterozygote deficiency was positive within quadrats, which was most likely a result of the Wahlund effect because the mites usually form small breeding colonies. Low population density and frequent inbreeding could also accelerate genetic differentiation among the breeding colonies. A short-range (2.4-3.6 m) positive autocorrelation and clear genetic cline among quadrat populations was detected within a bed. This suggests that gene flow was limited to a short range even if population density was substantially increased. Therefore, large-scale dispersal such as aerial dispersal contributed very little to gene flow in the greenhouse.

Relationship between exposure to vector bites and antibody responses to mosquito salivary gland extracts.

PubMed

Fontaine, Albin; Pascual, Aurélie; Orlandi-Pradines, Eve; Diouf, Ibrahima; Remoué, Franck; Pagès, Frédéric; Fusaï, Thierry; Rogier, Christophe; Almeras, Lionel

2011-01-01

Mosquito-borne diseases are major health problems worldwide. Serological responses to mosquito saliva proteins may be useful in estimating individual exposure to bites from mosquitoes transmitting these diseases. However, the relationships between the levels of these IgG responses and mosquito density as well as IgG response specificity at the genus and/or species level need to be clarified prior to develop new immunological markers to assess human/vector contact. To this end, a kinetic study of antibody levels against several mosquito salivary gland extracts from southeastern French individuals living in three areas with distinct ecological environments and, by implication, distinct Aedes caspius mosquito densities were compared using ELISA. A positive association was observed between the average levels of IgG responses against Ae. caspius salivary gland extracts and spatial Ae. caspius densities. Additionally, the average level of IgG responses increased significantly during the peak exposure to Ae. caspius at each site and returned to baseline four months later, suggesting short-lived IgG responses. The species-specificity of IgG antibody responses was determined by testing antibody responses to salivary gland extracts from Cx. pipiens, a mosquito that is present at these three sites at different density levels, and from two other Aedes species not present in the study area (Ae. aegypti and Ae. albopictus). The IgG responses observed against these mosquito salivary gland extracts contrasted with those observed against Ae. caspius salivary gland extracts, supporting the existence of species-specific serological responses. By considering different populations and densities of mosquitoes linked to environmental factors, this study shows, for the first time, that specific IgG antibody responses against Ae. caspius salivary gland extracts may be related to the seasonal and geographical variations in Ae. caspius density. Characterisation of such immunological-markers may allow the evaluation of the effectiveness of vector-control strategies or estimation of the risk of vector-borne disease transmission.

Relationship between Exposure to Vector Bites and Antibody Responses to Mosquito Salivary Gland Extracts

PubMed Central

Orlandi-Pradines, Eve; Diouf, Ibrahima; Remoué, Franck; Pagès, Frédéric; Fusaï, Thierry; Rogier, Christophe; Almeras, Lionel

2011-01-01

Mosquito-borne diseases are major health problems worldwide. Serological responses to mosquito saliva proteins may be useful in estimating individual exposure to bites from mosquitoes transmitting these diseases. However, the relationships between the levels of these IgG responses and mosquito density as well as IgG response specificity at the genus and/or species level need to be clarified prior to develop new immunological markers to assess human/vector contact. To this end, a kinetic study of antibody levels against several mosquito salivary gland extracts from southeastern French individuals living in three areas with distinct ecological environments and, by implication, distinct Aedes caspius mosquito densities were compared using ELISA. A positive association was observed between the average levels of IgG responses against Ae. caspius salivary gland extracts and spatial Ae. caspius densities. Additionally, the average level of IgG responses increased significantly during the peak exposure to Ae. caspius at each site and returned to baseline four months later, suggesting short-lived IgG responses. The species-specificity of IgG antibody responses was determined by testing antibody responses to salivary gland extracts from Cx. pipiens, a mosquito that is present at these three sites at different density levels, and from two other Aedes species not present in the study area (Ae. aegypti and Ae. albopictus). The IgG responses observed against these mosquito salivary gland extracts contrasted with those observed against Ae. caspius salivary gland extracts, supporting the existence of species-specific serological responses. By considering different populations and densities of mosquitoes linked to environmental factors, this study shows, for the first time, that specific IgG antibody responses against Ae. caspius salivary gland extracts may be related to the seasonal and geographical variations in Ae. caspius density. Characterisation of such immunological-markers may allow the evaluation of the effectiveness of vector-control strategies or estimation of the risk of vector-borne disease transmission. PMID:22195000

Reciprocal regulation of adipocyte and osteoblast differentiation of mesenchymal stem cells by Eupatorium japonicum prevents bone loss and adiposity increase in osteoporotic rats.

PubMed

Kim, Min-Ji; Jang, Woo-Seok; Lee, In-Kyoung; Kim, Jong-Keun; Seong, Ki-Seung; Seo, Cho-Rong; Song, No-Joon; Bang, Min-Hyuk; Lee, Young Min; Kim, Haeng Ran; Park, Ki-Moon; Park, Kye Won

2014-07-01

Pathological increases in adipogenic potential with decreases in osteogenic differentiation occur in osteoporotic bone marrow cells. Previous studies have shown that bioactive materials isolated from natural products can reciprocally regulate adipogenic and osteogenic fates of bone marrow cells. In this study, we showed that Eupatorium japonicum stem extracts (EJE) suppressed lipid accumulation and inhibited the expression of adipocyte markers in multipotent C3H10T1/2 and primary bone marrow cells. Conversely, EJE stimulated alkaline phosphatase activity and induced the expression of osteoblast markers in C3H10T1/2 and primary bone marrow cells. Daily oral administration of 50 mg/kg of EJE for 6 weeks to ovariectomized rats prevented body weight increase and bone mineral density decrease. Finally, activity-guided fractionation led to the identification of coumaric acid and coumaric acid methyl ester as bioactive anti-adipogenic and pro-osteogenic components in EJE. Taken together, our data indicate a promising possibility of E. japonicum as a functional food and as a therapeutic intervention for preventing osteoporosis and bone fractures.

Role of access to parks and markets with anthropometric measurements, biological markers, and a healthy lifestyle.

PubMed

Mena, Carlos; Fuentes, Eduardo; Ormazábal, Yony; Palomo-Vélez, Gonzalo; Palomo, Iván

2015-01-01

This study examined the association between access to urban green spaces and markets with anthropometric measurements, biological markers, sociodemographic, and healthy lifestyle. Geographic information systems were used to establish a correlation between environmental features and cardiovascular risk parameters. A total number of 832 (age range 18-74 years) individuals were selected for this study. Body mass index was significantly and positively related to the distance to parks (ρ = 0.079, p < 0.05), but negatively related to the distance to markets (ρ = -0.125, p < 0.05). In addition, waist circumference was similar and positively related to distance to parks (ρ = 0.097, p < 0.05) and negatively related to distance to markets (ρ = -0.092, p < 0.05). With respect to biochemical parameters, when there was an increase in the distance to markets, high-density lipoprotein cholesterol increased and glycemia decreased. The results of this study suggest the importance of the role of environmental factors such as parks and markets in the development of cardiovascular risk.

A High-Density Genetic Map with Array-Based Markers Facilitates Structural and Quantitative Trait Locus Analyses of the Common Wheat Genome

PubMed Central

Iehisa, Julio Cesar Masaru; Ohno, Ryoko; Kimura, Tatsuro; Enoki, Hiroyuki; Nishimura, Satoru; Okamoto, Yuki; Nasuda, Shuhei; Takumi, Shigeo

2014-01-01

The large genome and allohexaploidy of common wheat have complicated construction of a high-density genetic map. Although improvements in the throughput of next-generation sequencing (NGS) technologies have made it possible to obtain a large amount of genotyping data for an entire mapping population by direct sequencing, including hexaploid wheat, a significant number of missing data points are often apparent due to the low coverage of sequencing. In the present study, a microarray-based polymorphism detection system was developed using NGS data obtained from complexity-reduced genomic DNA of two common wheat cultivars, Chinese Spring (CS) and Mironovskaya 808. After design and selection of polymorphic probes, 13,056 new markers were added to the linkage map of a recombinant inbred mapping population between CS and Mironovskaya 808. On average, 2.49 missing data points per marker were observed in the 201 recombinant inbred lines, with a maximum of 42. Around 40% of the new markers were derived from genic regions and 11% from repetitive regions. The low number of retroelements indicated that the new polymorphic markers were mainly derived from the less repetitive region of the wheat genome. Around 25% of the mapped sequences were useful for alignment with the physical map of barley. Quantitative trait locus (QTL) analyses of 14 agronomically important traits related to flowering, spikes, and seeds demonstrated that the new high-density map showed improved QTL detection, resolution, and accuracy over the original simple sequence repeat map. PMID:24972598

A high-density intraspecific SNP linkage map of pigeonpea (Cajanas cajan L. Millsp.)

PubMed Central

Mandal, Paritra; Bhutani, Shefali; Dutta, Sutapa; Kumawat, Giriraj; Singh, Bikram Pratap; Chaudhary, A. K.; Yadav, Rekha; Gaikwad, K.; Sevanthi, Amitha Mithra; Datta, Subhojit; Raje, Ranjeet S.; Sharma, Tilak R.; Singh, Nagendra Kumar

2017-01-01

Pigeonpea (Cajanus cajan (L.) Millsp.) is a major food legume cultivated in semi-arid tropical regions including the Indian subcontinent, Africa, and Southeast Asia. It is an important source of protein, minerals, and vitamins for nearly 20% of the world population. Due to high carbon sequestration and drought tolerance, pigeonpea is an important crop for the development of climate resilient agriculture and nutritional security. However, pigeonpea productivity has remained low for decades because of limited genetic and genomic resources, and sparse utilization of landraces and wild pigeonpea germplasm. Here, we present a dense intraspecific linkage map of pigeonpea comprising 932 markers that span a total adjusted map length of 1,411.83 cM. The consensus map is based on three different linkage maps that incorporate a large number of single nucleotide polymorphism (SNP) markers derived from next generation sequencing data, using Illumina GoldenGate bead arrays, and genotyping with restriction site associated DNA (RAD) sequencing. The genotyping-by-sequencing enhanced the marker density but was met with limited success due to lack of common markers across the genotypes of mapping population. The integrated map has 547 bead-array SNP, 319 RAD-SNP, and 65 simple sequence repeat (SSR) marker loci. We also show here correspondence between our linkage map and published genome pseudomolecules of pigeonpea. The availability of a high-density linkage map will help improve the anchoring of the pigeonpea genome to its chromosomes and the mapping of genes and quantitative trait loci associated with useful agronomic traits. PMID:28654689

A high-density genetic map with array-based markers facilitates structural and quantitative trait locus analyses of the common wheat genome.

PubMed

Iehisa, Julio Cesar Masaru; Ohno, Ryoko; Kimura, Tatsuro; Enoki, Hiroyuki; Nishimura, Satoru; Okamoto, Yuki; Nasuda, Shuhei; Takumi, Shigeo

2014-10-01

The large genome and allohexaploidy of common wheat have complicated construction of a high-density genetic map. Although improvements in the throughput of next-generation sequencing (NGS) technologies have made it possible to obtain a large amount of genotyping data for an entire mapping population by direct sequencing, including hexaploid wheat, a significant number of missing data points are often apparent due to the low coverage of sequencing. In the present study, a microarray-based polymorphism detection system was developed using NGS data obtained from complexity-reduced genomic DNA of two common wheat cultivars, Chinese Spring (CS) and Mironovskaya 808. After design and selection of polymorphic probes, 13,056 new markers were added to the linkage map of a recombinant inbred mapping population between CS and Mironovskaya 808. On average, 2.49 missing data points per marker were observed in the 201 recombinant inbred lines, with a maximum of 42. Around 40% of the new markers were derived from genic regions and 11% from repetitive regions. The low number of retroelements indicated that the new polymorphic markers were mainly derived from the less repetitive region of the wheat genome. Around 25% of the mapped sequences were useful for alignment with the physical map of barley. Quantitative trait locus (QTL) analyses of 14 agronomically important traits related to flowering, spikes, and seeds demonstrated that the new high-density map showed improved QTL detection, resolution, and accuracy over the original simple sequence repeat map. © The Author 2014. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

The effects of twelve weeks of bed rest on bone histology, biochemical markers of bone turnover, and calcium homeostasis in eleven normal subjects

NASA Technical Reports Server (NTRS)

Zerwekh, J. E.; Ruml, L. A.; Gottschalk, F.; Pak, C. Y.; Blomqvist, C. G. (Principal Investigator)

1998-01-01

This study was undertaken to examine the effects of 12 weeks of skeletal unloading on parameters of calcium homeostasis, calcitropic hormones, bone histology, and biochemical markers of bone turnover in 11 normal subjects (9 men, 2 women; 34 +/- 11 years of age). Following an ambulatory control evaluation, all subjects underwent 12 weeks of bed rest. An additional metabolic evaluation was performed after 12 days of reambulation. Bone mineral density declined at the spine (-2.9%, p = 0.092) and at the hip (-3.8%, p = 0.002 for the trochanter). Bed rest prompted a rapid, sustained, significant increase in urinary calcium and phosphorus as well as a significant increase in serum calcium. Urinary calcium increased from a pre-bed rest value of 5.3 mmol/day to values as high as 73 mmol/day during bed rest. Immunoreactive parathyroid hormone and serum 1,25-dihydroxyvitamin D declined significantly during bed rest, although the mean values remained within normal limits. Significant changes in bone histology included a suppression of osteoblastic surface for cancellous bone (3.1 +/- 1.3% to 1.9 +/- 1.5%, p = 0.0142) and increased bone resorption for both cancellous and cortical bone. Cortical eroded surface increased from 3.5 +/- 1.1% to 7.3 +/- 4.0% (p = 0.018) as did active osteoclastic surface (0.2 +/- 0.3% to 0.7 +/- 0.7%, p = 0.021). Cancellous eroded surface increased from 2.1 +/- 1.1% to 4.7 +/- 2.2% (p = 0.002), while mean active osteoclastic surface doubled (0.2 +/- 0.2% to 0.4 +/- 0.3%, p = 0.020). Serum biochemical markers of bone formation (osteocalcin, bone-specific alkaline phosphatase, and type I procollagen extension peptide) did not change significantly during bed rest. Urinary biochemical markers of bone resorption (hydroxyproline, deoxypyridinoline, and N-telopeptide of type I collagen) as well as a serum marker of bone resorption (type I collagen carboxytelopeptide) all demonstrated significant increases during bed rest which declined toward normal during reambulation. Thus, under the conditions of this study, the human skeleton appears to respond to unloading by a rapid and sustained increase in bone resorption and a more subtle decrease in bone formation.

Switching from tenofovir to abacavir in HIV-1-infected patients with low bone mineral density: changes in bone turnover markers and circulating sclerostin levels.

PubMed

Negredo, Eugènia; Diez-Pérez, Adolfo; Bonjoch, Anna; Domingo, Pere; Pérez-Álvarez, Núria; Gutierrez, Mar; Mateo, Gracia; Puig, Jordi; Echeverría, Patricia; Escrig, Roser; Clotet, Bonaventura

2015-07-01

Tenofovir is involved in accelerated bone mineral density (BMD) loss. We recently published a hip BMD improvement at week 48 [+2.1% (95% CI: -0.6, 4.7) (P = 0.043)] in HIV-infected patients with osteopenia/osteoporosis randomized to switch from tenofovir to abacavir (n = 26), although without reaching statistical significance compared with those who maintained tenofovir (n = 28). Here, we present changes at week 48 in bone markers [C-terminal telopeptide of collagen type 1 (CTX), osteocalcin and procollagen type 1 N propeptide (P1NP)] as well as in circulating levels of three proteins involved in bone regulation [osteoprotegerin, receptor activator for NF-κB ligand (RANKL) and sclerostin, a selective regulator of bone formation through the Wnt pathway] in 44 of these patients. χ(2) or Fisher and Student t-tests were performed according to the distribution of the variables. Bone markers decreased only in the abacavir group [mean (SD) CTX changed from 0.543 (0.495) to 0.301 (0.306) ng/mL; mean (SD) osteocalcin changed from 23.72 (22.20) to 13.95 (12.40) ng/mL; and mean (SD) P1NP changed from 54.68 (54.52) to 28.65 (27.48) ng/mL (P < 0.001 in all cases)], reaching statistical significance between the groups at week 48. Osteoprotegerin did not vary, but sclerostin significantly increased in the abacavir group [from 29.53 (27.91) to 35.56 (34.59) pmol/L, P = 0.002]. No significant differences in osteoprotegerin and sclerostin were detected between the groups at week 48. RANKL values were below the limit of detection in all samples. The switch from tenofovir to abacavir seems to induce a positive effect on bone tissue, since bone turnover markers decreased. In addition, circulating sclerostin levels increased, a change associated with improved bone properties. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Effects of 16-month treatment with the cathepsin K inhibitor ONO-5334 on bone markers, mineral density, strength and histomorphometry in ovariectomized cynomolgus monkeys.

PubMed

Yamada, Hiroyuki; Ochi, Yasuo; Mori, Hiroshi; Nishikawa, Satoshi; Hashimoto, Yasuaki; Nakanishi, Yasutomo; Tanaka, Makoto; Bruce, Mark; Deacon, Steve; Kawabata, Kazuhito

2016-05-01

We examined the effects of ONO-5334, a cathepsin K inhibitor, on bone markers, BMD, strength and histomorphometry in ovariectomized (OVX) cynomolgus monkeys. ONO-5334 (1.2, 6 and 30mg/kg/day, p.o.), alendronate (0.05mg/kg/2weeks, i.v.), or vehicle was administered to OVX monkeys (all groups N=20) for 16months. A concurrent Sham group (N=20) was also treated with vehicle for 16months. OVX significantly increased bone resorption and formation markers and decreased BMD in lumbar vertebra, femoral neck, proximal tibia and distal radius. Alendronate suppressed these parameters to a level similar to that in the Sham-operated monkeys. ONO-5334 at doses 6 and 30mg/kg decreased bone resorption markers to a level roughly half of that in the Sham group, while keeping bone formation markers level above that in the Sham monkeys. Changes in DXA BMD confirmed that ONO-5334 at doses 6 and 30mg/kg increased BMD to a level greater than that in the Sham group in all examined sites. In the proximal tibia, in vivo pQCT analysis showed that ONO-5334 at doses 6 and 30mg/kg suppressed trabecular BMD loss to the sham level. However, ONO-5334 increased cortical BMD, cortical area and cortical thickness to a level greater than that in the Sham group, suggesting that ONO-5334 improves both cortical BMD and cortical geometry. Histomorphometric analysis revealed that ONO-5334 suppressed bone formation rate (BFR) at osteonal site in the midshaft femur but did not influence OVX-induced increase in BFR at either the periosteal or endocortical surfaces. Unlike alendronate, ONO-5334 increased osteoclasts surface (Oc.S/BS) and serum tartrate-resistant acid phosphatise 5b (TRAP5b) activity, highlighting the difference in the mode of action between these two drugs. Our results suggest that ONO-5334 has therapeutic potential not only in vertebral bones, but also in non-vertebral bones. Copyright © 2016 Elsevier Inc. All rights reserved.

The Relevance of Osteoclastic and Osteoblastic Activity Markers Follow-Up in Patients on Antiresorptive Osteoporosis Treatment.

PubMed

Smilic, Tanja N; Novakovic, Tatjana R; Markovic-Jovanovic, Snezana R; Smilic, Ljiljana L J; Mitic, Javorka S; Radunovic, Miodrag L

2017-11-02

In general, markers of bone formation and markers of bone resorption are changing synergistically, so the monitoring of any osteoclastic and any osteoblastic marker should reflect the rate of bone transformation. The aim of the study is to monitor the bone metabolism markers in postmenopausal women with osteoporosis and osteopenia along with the variations caused by the effects of bisphosphonate therapy. The study involved 55 women of average age of 57.95 years, with osteopenia or osteoporosis. The patients with osteoporosis were treated with bisphosphonates (75 mg once a week); the laboratory tests were performed before the treatment and 6 months later. Patients with osteopenia were evaluated at the first assessment and 6 months later. The tests included bone densitometry, dual-energy X-ray absorptiometry, osteocalcin, alkaline phosphatase, collagen 1 N-terminal pro-peptide (P1NP), and beta C telopeptide of type I collagen (CTX). The mean T-score was -2.80 ± 0.63 before therapy and -2.64 ± 0.45 6 months later (p < 0.001). Women with osteoporosis had elevated levels of osteocalcin and P1NP at the first assessment, whereas the alkaline phosphatase level did not change with the treatment. After the introduction of antiresorptive therapy, the levels of osteocalcin and P1NP significantly decreased (p < 0.001). In the group with osteopenia, the biochemical markers activity were increased in both assessments. In patients with osteoporosis, Beta-CTX was increased in the first evaluation, and decreased after treatment (p = 0.001). The results indicate that the assessment of biochemical markers of bone metabolism show excellent results in the assessment of prognosis, monitoring the course and the response to various treatment regimens of osteoporosis and evince strong correlation with standard densitometry and dual-energy X-ray absorptiometry procedures. P1NP and CTX show better diagnostic applicability compared with osteocalcin and alkaline phosphatase. The analysis of the activity of biochemical markers may obtain early information on the therapeutic response, before definitive assessment by bone density measurements. Copyright © 2017 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Biomarkers for osteoporosis management: utility in diagnosis, fracture risk prediction and therapy monitoring.

PubMed

Garnero, Patrick

2008-01-01

Osteoporosis is a systemic disease characterized by low bone mass and microarchitectural deterioration of bone tissue, resulting in an increased risk of fracture. While the level of bone mass can be estimated by measuring bone mineral density (BMD) using dual X-ray absorptiometry (DXA), its measurement does not capture all the risk factors for fracture. Quantitative changes in skeletal turnover can be assessed easily and non-invasively by the measurement of serum and urinary biochemical markers; the most sensitive markers include serum osteocalcin, bone specific alkaline phosphatase, the N-terminal propeptide of type I collagen for bone formation, and the crosslinked C- (CTX) and N- (NTX) telopeptides of type I collagen for bone resorption. Advances in our knowledge of bone matrix biochemistry, most notably of post-translational modifications in type I collagen, are likely to lead to the development of new biochemical markers that reflect changes in the material property of bone, an important determinant of bone strength. Among those, the measurement of the urinary ratio of native (alpha) to isomerized (beta) CTX - an index of bone matrix maturation - has been shown to be predictive of fracture risk independently of BMD and bone turnover. In postmenopausal osteoporosis, levels of bone resorption markers above the upper limit of the premenopausal range are associated with an increased risk of hip, vertebral, and nonvertebral fracture, independent of BMD. Therefore, the combined use of BMD measurement and biochemical markers is helpful in risk assessment, especially in those women who are not identified as at risk by BMD measurement alone. Levels of bone markers decrease rapidly with antiresorptive therapies, and the levels reached after 3-6 months of therapy have been shown to be more strongly associated with fracture outcome than changes in BMD. Preliminary studies indicate that monitoring changes of bone formation markers could also be useful to monitor anabolic therapies, including intermittent parathyroid hormone administration and, possibly, to improve adherence to treatment. Thus, repeated measurements of bone markers during therapy may help improve the management of osteoporosis in patients.

Phosphoinositide 3-kinase regulates maturation of lysosomes in rat hepatocytes.

PubMed Central

Mousavi, Seyed Ali; Brech, Andreas; Berg, Trond; Kjeken, Rune

2003-01-01

To obtain information about the role of phosphoinositide 3-kinase (PI3K) in the endocytic pathway in hepatocytes, the uptake and intracellular transport of asialo-orosomucoid (ASOR) was followed in cells treated with wortmannin or LY294002. The two inhibitors, at concentrations known to inhibit the enzyme, did not affect internalization or the number of surface asialoglycoprotein receptors, but they caused a paradoxical increase (approx. 50% above control values) in the degradation of ASOR labelled with [(125)I]tyramine cellobiose ([(125)I]TC). Wortmannin or LY204002 inhibited the autophagic sequestration of lactate dehydrogenase very effectively, and the enhanced degradation of [(125)I]TC-ASOR could be an indirect effect of reduced autophagy, as an amino acid mixture known to inhibit autophagy also caused increased degradation of [(125)I]TC-ASOR, and its effect was not additive to that of wortmannin or LY294002. Wortmannin or LY294002 had pronounced effects on the late parts of the endocytic pathway in the hepatocytes: first, dense lysosomes disappeared and were replaced by swollen vesicles; secondly, degradation of [(125)I]TC-ASOR took place in an organelle of lower buoyant density (in a sucrose gradient) than the bulk of lysosomes (identified in the gradient by lysosomal marker enzymes). With increasing length of incubation with wortmannin or LY294002, the density distributions of the lysosomal markers also shifted to lower density and gradually approached that of the labelled degradation products. The labelled degradation products formed from [(125)I]TC-labelled proteins were trapped at the site of formation, because they did not penetrate the vesicle membranes. The results obtained indicate that internalization and intracellular transport of ASOR to lysomes may take place in the absence of PI3K activity in rat hepatocytes. On the other hand, fusion of late endosomes with lysosomes seems to produce 'hybrid organelles' (active lysosomes) that are unable to mature into dense lysosomes. PMID:12646047

Bones and Crohn's: estradiol deficiency in men with Crohn's disease is not associated with reduced bone mineral density.

PubMed

Klaus, J; Reinshagen, M; Adler, G; Boehm, Bo; von Tirpitz, C

2008-10-23

Reduced bone mineral density (BMD) and osteoporosis are frequent in Crohn's disease (CD), but the underlying mechanisms are still not fully understood. Deficiency of sex steroids, especially estradiol (E2), is an established risk factor in postmenopausal osteoporosis. To assess if hormonal deficiencies in male CD patients are frequent we investigated both, sex steroids, bone density and bone metabolism markers. 111 male CD patients underwent osteodensitometry (DXA) of the spine (L1-L4). Disease related data were recorded. Disease activity was estimated using Crohn's disease activity index (CDAI). Testosterone (T), dihydrotestosterone (DHT), estradiol (E2), sex hormone binding globulin (SHBG), Osteocalcin and carboxyterminal cross-linked telopeptids (ICTP) were measured in 111 patients and 99 age-matched controls. Patients had lower T, E2 and SHBG serum levels (p < 0.001) compared to age-matched controls. E2 deficiency was seen in 30 (27.0%) and T deficiency in 3 (2.7%) patients but only in 5 (5.1%) and 1 (1%) controls. Patients with E2 deficiency had significantly decreased T and DHT serum levels. Use of corticosteroids for 3 of 12 months was associated with lower E2 levels (p < 0.05). Patients with life-time steroids >10 g had lower BMD. 32 (28.8%) patients showed osteoporosis, 55 (49.5%) osteopenia and 24 (21.6%) had normal BMD. Patients with normal or decreased BMD showed no significant difference in their hormonal status. No correlation between markers of bone turnover and sex steroids could be found. ICTP was increased in CD patients (p < 0.001), and patients with osteoporosis had higher ICTP levels than those with normal BMD. We found an altered hormonal status--i.e. E2 and, to a lesser extent T deficiency--in male CD patients but failed to show an association to bone density or markers of bone turnover. The role of E2 in the negative skeletal balance in males with CD, analogous to E2 deficiency in postmenopausal females, deserves further attention.

Characterization of focal cortical dysplasia with balloon cells by layer-specific markers: Evidence for differential vulnerability of interneurons.

PubMed

Nakagawa, Julia M; Donkels, Catharina; Fauser, Susanne; Schulze-Bonhage, Andreas; Prinz, Marco; Zentner, Josef; Haas, Carola A

2017-04-01

Focal cortical dysplasia (FCD) is a major cause of pharmacoresistant focal epilepsy. Little is known about the pathomechanisms underlying the characteristic cytoarchitectural abnormalities associated with FCD. In the present study, a broad panel of markers identifying layer-specific neuron subpopulations was applied to characterize dyslamination and structural alterations in FCD with balloon cells (FCD 2b). Pan-neuronal neuronal nuclei (NeuN) and layer-specific protein expression (Reelin, Calbindin, Calretinin, SMI32 (nonphosphorylated neurofilament H), Parvalbumin, transducin-like enhancer protein 4 (TLE4), and Vimentin) was studied by immunohistochemistry on paraffin sections of FCD2b cases (n = 22) and was compared to two control groups with (n = 7) or without epilepsy (n = 4 postmortem cases). Total and layer-specific neuron densities were systematically quantified by cell counting considering age at surgery and brain region. We show that in FCD2b total neuron densities across all six cortical layers were not significantly different from controls. In addition, we present evidence that a basic laminar arrangement of layer-specific neuron subtypes was preserved despite the severe disturbance of cortical structure. SMI32-positive pyramidal neurons showed no significant difference in total numbers, but a reduction in layers III and V. The densities of supragranular Calbindin- and Calretinin-positive interneurons in layers II and III were not different from controls, whereas Parvalbumin-expressing interneurons, primarily located in layer IV, were significantly reduced in numbers when compared to control cases without epilepsy. In layer VI, the density of TLE4-positive projection neurons was significantly increased. Altogether, these data show that changes in cellular composition mainly affect deep cortical layers in FCD2b. The application of a broad panel of markers defining layer-specific neuronal subpopulations revealed that in FCD2b neuronal diversity and a basic laminar arrangement are maintained despite the severe disturbance of cytoarchitecture. Moreover, it showed that Parvalbumin-positive, inhibitory interneurons are highly vulnerable in contrast to other interneuron subtypes, possibly related to the epileptic condition. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Trichome density of main stem is tightly linked to PepMoV resistance in chili pepper (Capsicum annuum L.).

PubMed

Kim, Hyun Jung; Han, Jung-Heon; Kim, Seungill; Lee, Heung Ryul; Shin, Jun-Sung; Kim, Jeong-Ho; Cho, Juok; Kim, Young Ho; Lee, Hee Jae; Kim, Byung-Dong; Choi, Doil

2011-04-01

A relationship between pepper trichome and pepper mottle virus (PepMoV) resistance was examined. In an intraspecific F(2) mapping population from the cross between Capsicum annuum CM334 (trichome-bearing and PepMoV resistant) and Chilsungcho (glabrous and PepMoV susceptible), major QTLs for both traits were identified by composite interval mapping in linkage group (LG) 24 corresponding a telomere region on pepper chromosome 10. Ptel1 of putative trichome enhancing locus was a common major QTL for trichome density on the main stem and calyx. Ptel1 apart from HpmsE031 at a 1.03 cM interval was specifically associated to the trichome density on the main stem, whereas Ptel2 near m104 marker on LG2 was specific for the calyx trichome. Epistatic analysis indicated that Ptel1 engaged in controlling the trichome density by mutual interactions with the organ-specific QTLs. For PepMoV resistance, two QTLs (Pep1 and Pep2) were identified on the LG 24. Pep1 was located with Ptel1 in the R-gene cluster (RGC) for potyvirus resistance including Pvr4 with broad spectrum resistance to potyviruses. Pep1 flanking TG420 marker seemed to be the major factors determining correlation with PepMoV resistance. These results indicate that the level of trichome density on pepper main stem can be used as a morphological marker for Pvr4 in pepper breeding.

Genome-Wide QTL Mapping for Wheat Processing Quality Parameters in a Gaocheng 8901/Zhoumai 16 Recombinant Inbred Line Population.

PubMed

Jin, Hui; Wen, Weie; Liu, Jindong; Zhai, Shengnan; Zhang, Yan; Yan, Jun; Liu, Zhiyong; Xia, Xianchun; He, Zhonghu

2016-01-01

Dough rheological and starch pasting properties play an important role in determining processing quality in bread wheat (Triticum aestivum L.). In the present study, a recombinant inbred line (RIL) population derived from a Gaocheng 8901/Zhoumai 16 cross grown in three environments was used to identify quantitative trait loci (QTLs) for dough rheological and starch pasting properties evaluated by Mixograph, Rapid Visco-Analyzer (RVA), and Mixolab parameters using the wheat 90 and 660 K single nucleotide polymorphism (SNP) chip assays. A high-density linkage map constructed with 46,961 polymorphic SNP markers from the wheat 90 and 660 K SNP assays spanned a total length of 4121 cM, with an average chromosome length of 196.2 cM and marker density of 0.09 cM/marker; 6596 new SNP markers were anchored to the bread wheat linkage map, with 1046 and 5550 markers from the 90 and 660 K SNP assays, respectively. Composite interval mapping identified 119 additive QTLs on 20 chromosomes except 4D; among them, 15 accounted for more than 10% of the phenotypic variation across two or three environments. Twelve QTLs for Mixograph parameters, 17 for RVA parameters and 55 for Mixolab parameters were new. Eleven QTL clusters were identified. The closely linked SNP markers can be used in marker-assisted wheat breeding in combination with the Kompetitive Allele Specific PCR (KASP) technique for improvement of processing quality in bread wheat.

Genome-Wide QTL Mapping for Wheat Processing Quality Parameters in a Gaocheng 8901/Zhoumai 16 Recombinant Inbred Line Population

PubMed Central

Jin, Hui; Wen, Weie; Liu, Jindong; Zhai, Shengnan; Zhang, Yan; Yan, Jun; Liu, Zhiyong; Xia, Xianchun; He, Zhonghu

2016-01-01

Dough rheological and starch pasting properties play an important role in determining processing quality in bread wheat (Triticum aestivum L.). In the present study, a recombinant inbred line (RIL) population derived from a Gaocheng 8901/Zhoumai 16 cross grown in three environments was used to identify quantitative trait loci (QTLs) for dough rheological and starch pasting properties evaluated by Mixograph, Rapid Visco-Analyzer (RVA), and Mixolab parameters using the wheat 90 and 660 K single nucleotide polymorphism (SNP) chip assays. A high-density linkage map constructed with 46,961 polymorphic SNP markers from the wheat 90 and 660 K SNP assays spanned a total length of 4121 cM, with an average chromosome length of 196.2 cM and marker density of 0.09 cM/marker; 6596 new SNP markers were anchored to the bread wheat linkage map, with 1046 and 5550 markers from the 90 and 660 K SNP assays, respectively. Composite interval mapping identified 119 additive QTLs on 20 chromosomes except 4D; among them, 15 accounted for more than 10% of the phenotypic variation across two or three environments. Twelve QTLs for Mixograph parameters, 17 for RVA parameters and 55 for Mixolab parameters were new. Eleven QTL clusters were identified. The closely linked SNP markers can be used in marker-assisted wheat breeding in combination with the Kompetitive Allele Specific PCR (KASP) technique for improvement of processing quality in bread wheat. PMID:27486464

High-Density Genetic Linkage Map Construction and Quantitative Trait Locus Mapping for Hawthorn (Crataegus pinnatifida Bunge).

PubMed

Zhao, Yuhui; Su, Kai; Wang, Gang; Zhang, Liping; Zhang, Jijun; Li, Junpeng; Guo, Yinshan

2017-07-14

Genetic linkage maps are an important tool in genetic and genomic research. In this study, two hawthorn cultivars, Qiujinxing and Damianqiu, and 107 progenies from a cross between them were used for constructing a high-density genetic linkage map using the 2b-restriction site-associated DNA (2b-RAD) sequencing method, as well as for mapping quantitative trait loci (QTL) for flavonoid content. In total, 206,411,693 single-end reads were obtained, with an average sequencing depth of 57× in the parents and 23× in the progeny. After quality trimming, 117,896 high-quality 2b-RAD tags were retained, of which 42,279 were polymorphic; of these, 12,951 markers were used for constructing the genetic linkage map. The map contained 17 linkage groups and 3,894 markers, with a total map length of 1,551.97 cM and an average marker interval of 0.40 cM. QTL mapping identified 21 QTLs associated with flavonoid content in 10 linkage groups, which explained 16.30-59.00% of the variance. This is the first high-density linkage map for hawthorn, which will serve as a basis for fine-scale QTL mapping and marker-assisted selection of important traits in hawthorn germplasm and will facilitate chromosome assignment for hawthorn whole-genome assemblies in the future.

The use of CT density changes at internal tissue interfaces to correlate internal organ motion with an external surrogate

NASA Astrophysics Data System (ADS)

Gaede, Stewart; Carnes, Gregory; Yu, Edward; Van Dyk, Jake; Battista, Jerry; Lee, Ting-Yim

2009-01-01

The purpose of this paper is to describe a non-invasive method to monitor the motion of internal organs affected by respiration without using external markers or spirometry, to test the correlation with external markers, and to calculate any time shift between the datasets. Ten lung cancer patients were CT scanned with a GE LightSpeed Plus 4-Slice CT scanner operating in a ciné mode. We retrospectively reconstructed the raw CT data to obtain consecutive 0.5 s reconstructions at 0.1 s intervals to increase image sampling. We defined regions of interest containing tissue interfaces, including tumour/lung interfaces that move due to breathing on multiple axial slices and measured the mean CT number versus respiratory phase. Tumour motion was directly correlated with external marker motion, acquired simultaneously, using the sample coefficient of determination, r2. Only three of the ten patients showed correlation higher than r2 = 0.80 between tumour motion and external marker position. However, after taking into account time shifts (ranging between 0 s and 0.4 s) between the two data sets, all ten patients showed correlation better than r2 = 0.8. This non-invasive method for monitoring the motion of internal organs is an effective tool that can assess the use of external markers for 4D-CT imaging and respiratory-gated radiotherapy on a patient-specific basis.

The use of CT density changes at internal tissue interfaces to correlate internal organ motion with an external surrogate.

PubMed

Gaede, Stewart; Carnes, Gregory; Yu, Edward; Van Dyk, Jake; Battista, Jerry; Lee, Ting-Yim

2009-01-21

The purpose of this paper is to describe a non-invasive method to monitor the motion of internal organs affected by respiration without using external markers or spirometry, to test the correlation with external markers, and to calculate any time shift between the datasets. Ten lung cancer patients were CT scanned with a GE LightSpeed Plus 4-Slice CT scanner operating in a ciné mode. We retrospectively reconstructed the raw CT data to obtain consecutive 0.5 s reconstructions at 0.1 s intervals to increase image sampling. We defined regions of interest containing tissue interfaces, including tumour/lung interfaces that move due to breathing on multiple axial slices and measured the mean CT number versus respiratory phase. Tumour motion was directly correlated with external marker motion, acquired simultaneously, using the sample coefficient of determination, r(2). Only three of the ten patients showed correlation higher than r(2) = 0.80 between tumour motion and external marker position. However, after taking into account time shifts (ranging between 0 s and 0.4 s) between the two data sets, all ten patients showed correlation better than r(2) = 0.8. This non-invasive method for monitoring the motion of internal organs is an effective tool that can assess the use of external markers for 4D-CT imaging and respiratory-gated radiotherapy on a patient-specific basis.

Biochemical bone turnover markers in diabetes mellitus - A systematic review.

PubMed

Starup-Linde, Jakob; Vestergaard, Peter

2016-01-01

Diabetes mellitus is associated with an increased risk of fractures, which is not explained by bone mineral density. Other markers as bone turnover markers (BTMs) may be useful. To assess the relationship between BTMs, diabetes, and fractures. A systematic literature search was conducted in August 2014. The databases searched were Medline at Pubmed and Embase. Medline at Pubmed was searched by "Diabetes Mellitus" (MESH) and "bone turnover markers" and Embase was searched using the Emtree by "Diabetes Mellitus" and "bone turnover", resulting in 611 studies. The eligibility criteria for the studies were to assess BTM in either type 1 diabetes (T1D) or type 2 diabetes (T2D) patients. Of the 611 eligible studies, removal of duplicates and screening by title and abstract lead to 114 potential studies for full-text review. All these studies were full-text screened for eligibility and 45 studies were included. Two additional studies were added from other sources. Among the 47 studies included there were 1 meta-analysis, 29 cross-sectional studies, 13 randomized controlled trials, and 4 longitudinal studies. Both T1D and T2D were studied. Most studies reported fasting BTM and excluded renal disease. Markers of bone resorption and formation seem to be lower in diabetes patients. Bone specific alkaline phosphatase is normal or increased, which suggests that the matrix becomes hypermineralized in diabetes patients. The BTMs: C-terminal cross-link of collagen, insulin-like growth factor-1, and sclerostin may potentially predict fractures, but longitudinal trials are needed. This article is part of a Special Issue entitled Bone and diabetes. Copyright © 2015 Elsevier Inc. All rights reserved.

Hypothalamic amenorrhea in young women with underlying polycystic ovary syndrome.

PubMed

Sum, Melissa; Warren, Michelle P

2009-12-01

The purpose of this study was to compare the hormonal/clinical profiles and markers of bone health of women with hypothalamic amenorrhea (HA) to women with suspected HA and underlying polycystic ovary syndrome (PCOS). The results indicate that compared to women with HA, women with HA and underlying PCOS exhibit higher body mass index (BMI), bone mineral densities, and incidence of hyperandrogenism, that they may exhibit increased hyperandrogenism and irregular menses with weight gain, and that they remain at similar risk for osteopenia and osteoporosis.

The application of GBS markers for extending the dense genetic map of rye (Secale cereale L.) and the localization of the Rfc1 gene restoring male fertility in plants with the C source of sterility-inducing cytoplasm.

PubMed

Milczarski, Paweł; Hanek, Monika; Tyrka, Mirosław; Stojałowski, Stefan

2016-11-01

Genotyping by sequencing (GBS) is an efficient method of genotyping in numerous plant species. One of the crucial steps toward the application of GBS markers in crop improvement is anchoring them on particular chromosomes. In rye (Secale cereale L.), chromosomal localization of GBS markers has not yet been reported. In this paper, the application of GBS markers generated by the DArTseq platform for extending the high-density map of rye is presented. Additionally, their application is used for the localization of the Rfc1 gene that restores male fertility in plants with the C source of sterility-inducing cytoplasm. The total number of markers anchored on the current version of the map is 19,081, of which 18,132 were obtained from the DArTseq platform. Numerous markers co-segregated within the studied mapping population, so, finally, only 3397 unique positions were located on the map of all seven rye chromosomes. The total length of the map is 1593 cM and the average distance between markers is 0.47 cM. In spite of the resolution of the map being not very high, it should be a useful tool for further studies of the Secale cereale genome because of the presence on this map of numerous GBS markers anchored for the first time on rye chromosomes. The Rfc1 gene was located on high-density maps of the long arm of the 4R chromosome obtained for two mapping populations. Genetic maps were composed of DArT, DArTseq, and PCR-based markers. Consistent mapping results were obtained and DArTs tightly linked to the Rfc1 gene were successfully applied for the development of six new PCR-based markers useful in marker-assisted selection.

Short communication: Improving the accuracy of genomic prediction of body conformation traits in Chinese Holsteins using markers derived from high-density marker panels.

PubMed

Song, H; Li, L; Ma, P; Zhang, S; Su, G; Lund, M S; Zhang, Q; Ding, X

2018-06-01

This study investigated the efficiency of genomic prediction with adding the markers identified by genome-wide association study (GWAS) using a data set of imputed high-density (HD) markers from 54K markers in Chinese Holsteins. Among 3,056 Chinese Holsteins with imputed HD data, 2,401 individuals born before October 1, 2009, were used for GWAS and a reference population for genomic prediction, and the 220 younger cows were used as a validation population. In total, 1,403, 1,536, and 1,383 significant single nucleotide polymorphisms (SNP; false discovery rate at 0.05) associated with conformation final score, mammary system, and feet and legs were identified, respectively. About 2 to 3% genetic variance of 3 traits was explained by these significant SNP. Only a very small proportion of significant SNP identified by GWAS was included in the 54K marker panel. Three new marker sets (54K+) were herein produced by adding significant SNP obtained by linear mixed model for each trait into the 54K marker panel. Genomic breeding values were predicted using a Bayesian variable selection (BVS) model. The accuracies of genomic breeding value by BVS based on the 54K+ data were 2.0 to 5.2% higher than those based on the 54K data. The imputed HD markers yielded 1.4% higher accuracy on average (BVS) than the 54K data. Both the 54K+ and HD data generated lower bias of genomic prediction, and the 54K+ data yielded the lowest bias in all situations. Our results show that the imputed HD data were not very useful for improving the accuracy of genomic prediction and that adding the significant markers derived from the imputed HD marker panel could improve the accuracy of genomic prediction and decrease the bias of genomic prediction. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Tyrosine levels are associated with insulin resistance in patients with nonalcoholic fatty liver disease

PubMed Central

Kawanaka, Miwa; Nishino, Ken; Oka, Takahito; Urata, Noriyo; Nakamura, Jun; Suehiro, Mitsuhiko; Kawamoto, Hirofumi; Chiba, Yasutaka; Yamada, Gotaro

2015-01-01

Objective Amino acid imbalance is often found in patients with cirrhosis, and this imbalance is associated with insulin resistance. However, the mechanism underlying the relationship between amino acid imbalance and insulin resistance remains unclear. We evaluated serum amino acid concentrations in patients with nonalcoholic fatty liver disease to determine if any of the levels of amino acids were associated with the biochemical markers and fibrosis stage of nonalcoholic steatohepatitis (NASH). Methods In 137 patients with nonalcoholic fatty liver disease who underwent liver biopsy, plasma levels of branched-chain amino acid (BCAA), tyrosine (Tyr), and the BCAA-to-Tyr ratio values were determined using mass spectroscopy. These values were then assessed for associations with fibrosis stage, anthropometric markers (age, sex, and body mass index), biochemical markers (alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, albumin, platelet count, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and glycosylated hemoglobin), and relevant disease-specific biomarkers (homeostasis model assessment of insulin resistance [HOMA-IR], serum iron, ferritin, leptin, adiponectin, high-sensitivity C-reactive protein, and hyaluronic acid). Results Serum albumin levels, plasma BCAA levels, and BCAA-to-Tyr ratio values were negatively associated with the fibrosis stage. In contrast, Tyr levels increased with increasing fibrotic staging. Tyr levels were also correlated with HOMA-IR results. Conclusion Plasma BCAA levels in patients with NASH decreased with increasing liver fibrosis, while Tyr levels increased with increasing fibrotic stage. These results suggest that amino acid imbalance and insulin resistance are intimately involved in a complex pathogenic mechanism for NASH. PMID:26082668

Development of a dense SNP-based linkage map of an apple rootstock progeny using the Malus Infinium whole genome genotyping array

PubMed Central

2012-01-01

Background A whole-genome genotyping array has previously been developed for Malus using SNP data from 28 Malus genotypes. This array offers the prospect of high throughput genotyping and linkage map development for any given Malus progeny. To test the applicability of the array for mapping in diverse Malus genotypes, we applied the array to the construction of a SNP-based linkage map of an apple rootstock progeny. Results Of the 7,867 Malus SNP markers on the array, 1,823 (23.2%) were heterozygous in one of the two parents of the progeny, 1,007 (12.8%) were heterozygous in both parental genotypes, whilst just 2.8% of the 921 Pyrus SNPs were heterozygous. A linkage map spanning 1,282.2 cM was produced comprising 2,272 SNP markers, 306 SSR markers and the S-locus. The length of the M432 linkage map was increased by 52.7 cM with the addition of the SNP markers, whilst marker density increased from 3.8 cM/marker to 0.5 cM/marker. Just three regions in excess of 10 cM remain where no markers were mapped. We compared the positions of the mapped SNP markers on the M432 map with their predicted positions on the ‘Golden Delicious’ genome sequence. A total of 311 markers (13.7% of all mapped markers) mapped to positions that conflicted with their predicted positions on the ‘Golden Delicious’ pseudo-chromosomes, indicating the presence of paralogous genomic regions or mis-assignments of genome sequence contigs during the assembly and anchoring of the genome sequence. Conclusions We incorporated data for the 2,272 SNP markers onto the map of the M432 progeny and have presented the most complete and saturated map of the full 17 linkage groups of M. pumila to date. The data were generated rapidly in a high-throughput semi-automated pipeline, permitting significant savings in time and cost over linkage map construction using microsatellites. The application of the array will permit linkage maps to be developed for QTL analyses in a cost-effective manner, and the identification of SNPs that have been assigned erroneous positions on the ‘Golden Delicious’ reference sequence will assist in the continued improvement of the genome sequence assembly for that variety. PMID:22631220

NeuN+ Neuronal Nuclei in Non-Human Primate Prefrontal Cortex and Subcortical White Matter After Clozapine Exposure

PubMed Central

Halene, Tobias B.; Kozlenkov, Alexey; Jiang, Yan; Mitchell, Amanda; Javidfar, Behnam; Dincer, Aslihan; Park, Royce; Wiseman, Jennifer; Croxson, Paula; Giannaris, Eustathia Lela; Hof, Patrick R.; Roussos, Panos; Dracheva, Stella; Hemby, Scott E.; Akbarian, Schahram

2016-01-01

Increased neuronal densities in subcortical white matter have been reported for some cases with schizophrenia. The underlying cellular and molecular mechanisms remain unresolved. We exposed 26 young adult macaque monkeys for 6 months to either clozapine, haloperidol or placebo and measured by structural MRI frontal gray and white matter volumes before and after treatment, followed by observer-independent, flow-cytometry-based quantification of neuronal and non-neuronal nuclei and molecular fingerprinting of cell-type specific transcripts. After clozapine exposure, the proportion of nuclei expressing the neuronal marker NeuN increased by approximately 50% in subcortical white matter, in conjunction with a more subtle and non-significant increase in overlying gray matter. Numbers and proportions of nuclei expressing the oligodendrocyte lineage marker, OLIG2, and cell-type specific RNA expression patterns, were maintained after antipsychotic drug exposure. Frontal lobe gray and white matter volumes remained indistinguishable between antipsychotic-drug-exposed and control groups. Chronic clozapine exposure increases the proportion of NeuN+ nuclei in frontal subcortical white matter, without alterations in frontal lobe volumes or cell type-specific gene expression. Further exploration of neurochemical plasticity in non-human primate brain exposed to antipsychotic drugs is warranted. PMID:26776227

Serum bone alkaline phosphatase and calcaneus bone density predict fractures: a prospective study.

PubMed

Ross, P D; Kress, B C; Parson, R E; Wasnich, R D; Armour, K A; Mizrahi, I A

2000-01-01

The aim of this study was to assess the ability of serum bone-specific alkaline phosphatase (bone ALP), creatinine-corrected urinary collagen crosslinks (CTx) and calcaneus bone mineral density (BMD) to identify postmenopausal women who have an increased risk of osteoporotic fractures. Calcaneus BMD and biochemical markers of bone turnover (serum bone ALP and urinary CTx) were measured in 512 community-dwelling postmenopausal women (mean age at baseline 69 years) participating in the Hawaii Osteoporosis Study. New spine and nonspine fractures subsequent to the BMD and biochemical bone markers measurements were recorded over an average of 2.7 years. Lateral spinal radiographs were used to identify spine fractures. Nonspine fractures were identified by self-report at the time of each examination. During the 2.7-year follow-up, at least one osteoporotic fracture occurred in 55 (10.7%) of the 512 women. Mean baseline serum bone ALP and urinary CTx were significantly higher among women who experienced an osteoporotic fracture compared with those women who did not fracture. In separate age-adjusted logistic regression models, serum bone ALP, urinary CTx and calcaneus BMD were each significantly associated with new fractures (odds ratios of 1.53, 1.54 and 1.61 per SD, respectively). Multiple variable logistic regression analysis identified BMD and serum bone ALP as significant predictors of fracture (p = 0.002 and 0.017, respectively). The results from this investigation indicate that increased bone turnover is significantly associated with an increased risk of osteoporotic fracture in postmenopausal women. This association is similar in magnitude and independent of that observed for BMD.

High doses of vitamin C plus E reduce strength training-induced improvements in areal bone mineral density in elderly men.

PubMed

Stunes, Astrid Kamilla; Syversen, Unni; Berntsen, Sveinung; Paulsen, Gøran; Stea, Tonje H; Hetlelid, Ken J; Lohne-Seiler, Hilde; Mosti, Mats Peder; Bjørnsen, Thomas; Raastad, Truls; Haugeberg, Glenn

2017-06-01

Resistance training is beneficial for maintaining bone mass. We aimed to investigate the skeletal effects of high doses of antioxidants [vitamin C + E (α-tocopherol)] supplementation during 12-week supervised strength training in healthy, elderly men METHODS: Design: double-blinded randomized placebo-controlled study. Participants followed a supervised, undulating periodic exercise program with weekly adjusted load: 3 sessions/week and 3-15 repetitions maximum (RM) sets/exercise. The control group (CG, n = 17, 67 ± 5 years) received placebo and the antioxidant group (AO, n = 16, 70 ± 7 years) 1000 mg vitamin C + 235 mg vitamin E, daily. Areal bone mineral density (aBMD) at whole body, lumbar spine (L1-L4), total hip, and femoral neck were measured by dual energy X-ray absorptiometry and muscle strength by 1RM. Serum analyses of bone-related factors and adipokines were performed. In the CG, total hip aBMD increased by 1.0% (CI: 0.3-1.7) versus pretest and lumbar spine aBMD increased by 0.9% (CI: -0.2 to 2.0) compared to the AO. In the CG, there was an increase in serum concentrations of insulin-like growth factor 1 [+27.3% (CI: -0.3 to 54.9)] and leptin [+31.2% (CI: 9.8-52.6)) versus pretest, and a decrease in sclerostin [-9.9% (CI: 4.4-15.3)] versus pretest and versus AO. Serum bone formation markers P1NP and osteocalcin increased in both groups, while the bone resorption marker CTX-1 remained unchanged. High doses of antioxidant supplementations may constrain the favorable skeletal benefits of 12 weeks of resistance exercise in healthy elderly men.

Regulation of osteoarthritis by omega-3 (n-3) polyunsaturated fatty acids in a naturally occurring model of disease

PubMed Central

Knott, L.; Avery, N.C.; Hollander, A.P.; Tarlton, J.F.

2011-01-01

Summary Objective To examine effects of high omega-3 (n-3) polyunsaturated fatty acid (PUFA) diets on development of osteoarthritis (OA) in a spontaneous guinea pig model, and to further characterise pathogenesis in this model. Modern diets low in n-3 PUFAs have been linked with increases in inflammatory disorders, possibly including OA. However, n-3 is also thought to increases bone density, which is a possible contributing factor in OA. Therefore we aim to determine the net influence of n-3 in disease development. Method OA-prone Dunkin-Hartley (DH) Guinea pigs were compared with OA-resistant Bristol Strain-2s (BS2) each fed a standard or an n-3 diet from 10 to 30 weeks (10/group). We examined cartilage and subchondral bone pathology by histology, and biochemistry, including collagen cross-links, matrix metalloproteinases (MMPs), alkaline phosphatase, glycosaminoglycan (GAG), and denatured type II collagen. Results Dietary n-3 reduced disease in OA-prone animals. Most cartilage parameters were modified by n-3 diet towards those seen in the non-pathological BS2 strain – significantly active MMP-2, lysyl-pyridinoline and total collagen cross-links – the only exception being pro MMP-9 which was lower in the BS2, yet increased with n-3. GAG content was higher and denatured type II lower in the n-3 group. Subchondral bone parameters in the DH n-3 group also changed towards those seen in the non-pathological strain, significantly calcium:phosphate ratios and epiphyseal bone density. Conclusion Dietary n-3 PUFA reduced OA in the prone strain, and most disease markers were modified towards those of the non-OA strain, though not all significantly so. Omega-3 did not increase markers of pathology in either strain. PMID:21723952

Effects of improved fat meat products consumption on emergent cardiovascular disease markers of male volunteers at cardiovascular risk.

PubMed

Celada, Paloma; Sánchez-Muniz, Francisco J; Delgado-Pando, Gonzalo; Bastida, Sara; Rodilla, Manuel Espárrago; Jiménez-Colmenero, Francisco; Olmedilla-Alonso, Begoña

2016-12-01

High meat-product consumption has been related to cardiovascular disease (CVD). However, previous results suggest the benefits of consuming improved fat meat products on lipoprotein-cholesterol and anthropometric measurements. Present study aims to assess the effect of consuming different Pâté and Frankfurter formulations on emergent CVD biomarkers in male volunteers at increased CVD risk. Eighteen male volunteers with at least two CVD risk factors were enrolled in a sequentially controlled study where different pork-products were tested: reduced-fat (RF), omega-3-enriched-RF (n-3RF), and normal-fat (NF). Pork-products were consumed during 4-week periods separated by 4-week washout. The cardiometabolic index (CI), oxidized low density lipoproteins (oxLDL), apolipoproteins (Apo) A1 and B, homocysteine (tHcys), arylesterase (AE), C-reactive Protein (CRP), tumor necrotic factor-alpha (TNFα), and lipoprotein (a) (Lp(a)) were tested and some other related ratios calculated. AE, oxLDL and Lp(a), AE/HDLc, LDLc/Apo B, and AE/oxLDL rate of change were differently affected (P<0.01) by pork-products consumption. RF increased (P < 0.05) AE, AE/HDLc and AE/oxLDL ratios and decreased TNFα, tHcys; n-3RF increased (P < 0.001) AE, AE/HDLc and AE/oxLDL ratios and decreased (P < 0.05) Lp(a); while NF increased (P<0.05) oxLDL and Lp(a) levels. In conclusion, RF and n-3RF products affected positively the level of some emergent CVD markers. The high regular consumption of NF-products should be limited as significantly increased Lp(a) and oxLDL values. The high variability in response observed for some markers suggests the need to perform more studies to identify targets for RF- and n-3RF-products. Graphical Abstract Emergent CVD markers.

Plasma visfatin level in lean women with PCOS: relation to proinflammatory markers and insulin resistance.

PubMed

Gen, Ramazan; Akbay, Esen; Muslu, Necati; Sezer, Kerem; Cayan, Filiz

2009-04-01

The present study was undertaken to investigate the association between plasma visfatin concentrations and inflammatory markers such as interleukin-6 (IL-6) and high-sensitive C-reactive protein (hsCRP) in company with several metabolic parameters in lean women with polycystic ovary syndrome (PCOS). The study group consisted of 21 lean women with PCOS (BMI 20.74 +/- 1.74 kg/m(2)) and 15 healthy, normally menstruating women (BMI 20.85 +/- 2.08 kg/m(2) control group). PCOS was defined according to the Rotterdam criteria. Visfatin, IL-6, hsCRP, hyperandrogenism markers and metabolic markers were examined in all PCOS and control women. Plasma visfatin level in the PCOS group was higher than that in the control group. Plasma hsCRP and IL-6 levels in PCOS group were similar with the control group. Plasma visfatin levels were positively associated with total cholesterol, high density lipoprotein, hirsutism score, total testosterone and FAI. Plasma visfatin level was negatively associated with SHBG. However, there were no correlation between plasma visfatin level and IL-6 and hsCRP. In multivariate regression analyses, only FAI and high density lipoprotein-cholesterol (HDL-C) showed a significant association with serum visfatin. Our data indicates that plasma visfatin levels are associated with HDL-C and markers of hyperandrogenism, but it is not associated with proinflammatory markers and insulin resistance in lean women with PCOS.

Effect of 1-year dietary supplementation with vitaminized olive oil on markers of bone turnover and oxidative stress in healthy post-menopausal women.

PubMed

Mazzanti, Laura; Battino, Maurizio; Nanetti, Laura; Raffaelli, Francesca; Alidori, Alessandro; Sforza, Giulia; Carle, Flavia; Quagliarini, Veronica; Cester, Nelvio; Vignini, Arianna

2015-11-01

Osteoporosis represents a serious health problem worldwide associated with an increased risk of fractures and mortality. Nutrition should form part of bone disease prevention strategies, especially in the light of the population ageing and the diet effect on bone health. Thus the study aimed at verifying whether 1 year of oral supplementation with either extra virgin olive oil (VOO) enriched with vitamins D3, K1 and B6 (VitVOO) or VOO used as placebo (PlaVOO) is able to modify some bone turnover and oxidative stress markers. Bone mineral density (BMD) was assessed in 60 healthy post-menopausal women together with the bone vitamin K status by measuring undercarboxylated osteocalcine (ucOC) plasma levels, the ratio between ucOC and carboxylated osteocalcine (UCR) and the relations with oxidative stress markers. After 1 year (T 1), subjects taking VitVOO showed lower ucOC levels than those taking PlaVOO; the same trend was found for UCR. As far as BMD is concerned, a significant increase in T-score at T 1 in VitVOO subjects compared to PlaVOO was found. All oxidative stress markers as thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes showed a significant reduction after VitVOO supplementation, whilst plasma total antioxidant capacity values was significantly increased in VitVOO group compared to PlaVOO group at T 1. It might be suggested that the use of VitVOO in the diet of post-menopausal women could represent a proper tool for bone protection and a useful strategy against oxidative stress and related diseases, thus confirming the antioxidant role played by the added vitamins.

Effect of electromigration-induced back stress gradient on nanoindentation marker movement in SnAgCu solder joints

NASA Astrophysics Data System (ADS)

Xu, Luhua; Pang, John H. L.; Tu, K. N.

2006-11-01

The electromigration-induced back stress in Pb-free SnAgCu solder was studied by an area array of nanoindentation markers on the cross section of a solder joint. The marker movements driven by combined electron wind force and electromigration-induced back stress gradient were measured at different locations. The back stress gradient was determined from the observation of marker motion using the proposed model. With the applied current density of 104A/cm2 at 125°C, the stress gradient near the anode is 97kPa/μm.

Angiogenesis Markers in Gynecological Tumors and Patents for Anti-Angiogenic Approach: Review.

PubMed

Abdalla, Douglas R; Simoens, Cindy; Bogers, John-Paul; Murta, Eddie F C; Michelin, Marcia A

2015-01-01

The formation of a tumor-associated vascular network is an important step in understanding the stages of tumor progression. This review aims to highlight the main markers of induction, proliferation and inhibition of angiogenesis, as well as the quantification of microvessel density, correlated with preclinical and clinical research in gynecologic cancers and also discussed related patents. Studies show that in the most advanced cases of gynecological cancers, biomarkers such as VEGF (Vascular Endothelial Growth Factor), MMP (Matrix Metalloproteinase), CD105 (Endoglin), TIMP (tissue inhibitors of metalloproteinases) and VASH (Vasohibin) are more expressed compared to healthy individuals. Continuous evaluation of these biomarkers in cancer cases could serve in the future as a basis for development of new therapeutic approaches, leading to a good response to cancer treatment, and thus increase survival of cancer patients.

CD44 Promotes Inflammation and Extracellular Matrix Production During Arteriovenous Fistula Maturation.

PubMed

Kuwahara, Go; Hashimoto, Takuya; Tsuneki, Masayuki; Yamamoto, Kota; Assi, Roland; Foster, Trenton R; Hanisch, Jesse J; Bai, Hualong; Hu, Haidi; Protack, Clinton D; Hall, Michael R; Schardt, John S; Jay, Steven M; Madri, Joseph A; Kodama, Shohta; Dardik, Alan

2017-06-01

Arteriovenous fistulae (AVF) remain the optimal conduit for hemodialysis access but continue to demonstrate poor patency and poor rates of maturation. We hypothesized that CD44, a widely expressed cellular adhesion molecule that serves as a major receptor for extracellular matrix components, promotes wall thickening and extracellular matrix deposition during AVF maturation. AVF were created via needle puncture in wild-type C57BL/6J and CD44 knockout mice. CD44 mRNA and protein expression was increased in wild-type AVF. CD44 knockout mice showed no increase in AVF wall thickness (8.9 versus 26.8 μm; P =0.0114), collagen density, and hyaluronic acid density, but similar elastin density when compared with control AVF. CD44 knockout mice also showed no increase in vascular cell adhesion molecule-1 expression, intercellular adhesion molecule-1 expression, and monocyte chemoattractant protein-1 expression in the AVF compared with controls; there were also no increased M2 macrophage markers (transglutaminase-2: 81.5-fold, P =0.0015; interleukin-10: 7.6-fold, P =0.0450) in CD44 knockout mice. Delivery of monocyte chemoattractant protein-1 to CD44 knockout mice rescued the phenotype with thicker AVF walls (27.2 versus 14.7 μm; P =0.0306), increased collagen density (2.4-fold; P =0.0432), and increased number of M2 macrophages (2.1-fold; P =0.0335). CD44 promotes accumulation of M2 macrophages, extracellular matrix deposition, and wall thickening during AVF maturation. These data show the association of M2 macrophages with wall thickening during AVF maturation and suggest that enhancing CD44 activity may be a strategy to increase AVF maturation. © 2017 American Heart Association, Inc.

CD44 Promotes Inflammation and Extracellular Matrix Production During Arteriovenous Fistula Maturation

PubMed Central

Kuwahara, Go; Hashimoto, Takuya; Tsuneki, Masayuki; Yamamoto, Kota; Assi, Roland; Foster, Trenton R; Hanisch, Jesse J; Bai, Hualong; Hu, Haidi; Protack, Clinton D; Hall, Michael R; Schardt, John S; Jay, Steven M; Madri, Joseph A; Kodama, Shohta; Dardik, Alan

2017-01-01

Objective Arteriovenous fistulae (AVF) remain the optimal conduit for hemodialysis access but continue to demonstrate poor patency and poor rates of maturation. We hypothesized that CD44, a widely expressed cellular adhesion molecule that serves as a major receptor for extracellular matrix (ECM) components, promotes wall thickening and ECM deposition during AVF maturation. Approach and Results AVF were created via needle puncture in wild-type (WT) C57BL/6J and CD44 knockout (KO) mice. CD44 mRNA and protein expression was increased in WT AVF. CD44 KO mice showed no increase in AVF wall thickness (8.9 μm vs. 26.8 μm; P = 0.0114), collagen density, and hyaluronic acid density, but similar elastin density when compared to control AVF. CD44 KO mice also showed no increase in VCAM-1 expression, ICAM-1 expression and MCP-1 expression in the AVF compared to controls; there were also no increased M2 macrophage markers (TGM2: 81.5 fold, P = 0.0015; IL-10: 7.6 fold, P = 0.0450) in CD44 KO mice. Delivery of MCP-1 to CD44 KO mice rescued the phenotype with thicker AVF walls (27.2 μm vs. 14.7 μm; P = 0.0306), increased collagen density (2.4 fold; P = 0.0432), and increased number of M2 macrophages (2.1 fold; P = 0.0335). Conclusions CD44 promotes accumulation of M2 macrophages, ECM deposition and wall thickening during AVF maturation. These data show the association of M2 macrophages with wall thickening during AVF maturation and suggest that enhancing CD44 activity may be a strategy to increase AVF maturation. PMID:28450292

Changes in osteocyte density correspond with changes in osteoblast and osteoclast activity in an osteoporotic sheep model.

PubMed

Zarrinkalam, M R; Mulaibrahimovic, A; Atkins, G J; Moore, R J

2012-04-01

Histomorphometric assessment of trabecular bone in osteoporotic sheep showed that bone volume, osteoid surface area, bone formation rate, and osteocyte density were reduced. In contrast, eroded surface area and empty lacunae density were increased. Changes in osteocyte density correlated with changes in osteoblast and osteoclast activity. Osteocytes contribute to the regulation of the activity of osteoclasts and osteoblasts that together control bone mass. Osteocytes therefore likely play a role in the loss of bone mass associated with osteoporosis. The purpose of this study was to investigate the relationships between osteocyte lacunar density and other bone histomorphometric parameters in the iliac crest (IC) and lumbar spine (LS) of osteoporotic sheep. Osteoporosis was induced in ten mature ewes by an established protocol involving a combination of ovariectomy, dexamethasone injection, and low calcium diet for 6 months. Five ewes were used as controls. Post-mortem IC and LS biopsies were collected and processed for further histomorphometric assessment. Bone volume, osteoid surface, and bone formation rate in the IC and LS of osteoporotic sheep were reduced compared to those of the controls. In contrast, eroded surface area was increased in osteoporotic sheep. In the osteoporotic group, osteocyte density was reduced in the LS region and to a greater extent in the IC region. The empty osteocyte lacunae were increased 1.7-fold in LS and 2.1-fold in IC in the osteoporotic group. The osteocyte density correlated positively with markers of osteoblast activity and negatively with those of osteoclast activity. Depletion of osteocytes and an increase in the empty lacunae could be important factors contributing to bone loss in this model since they may adversely affect intercellular communication between osteoblasts and osteoclasts. The regional differences in histology suggest that there may be different pathological mechanisms operating at different anatomical sites.

The PPAR alpha gene is associated with triglyceride, low-density cholesterol and inflammation marker response to fenofibrate intervention: the GOLDN study

USDA-ARS?s Scientific Manuscript database

As a peroxisome proliferator-activated receptor alpha (PPAR Alpha) agonist, fenofibrate favorably modulates dyslipidemia and inflammation markers, which are associated with cardiovascular risk. To determine whether variation in the PPAR Alpha receptor gene was associated with lipid and inflammatory ...

Cortical and Trabecular Bone Microstructure Did Not Recover at Weight-Bearing Skeletal Sites and Progressively Deteriorated at Non-Weight-Bearing Sites During the Year Following International Space Station Missions.

PubMed

Vico, Laurence; van Rietbergen, Bert; Vilayphiou, Nicolas; Linossier, Marie-Thérèse; Locrelle, Hervé; Normand, Myriam; Zouch, Mohamed; Gerbaix, Maude; Bonnet, Nicolas; Novikov, Valery; Thomas, Thierry; Vassilieva, Galina

2017-10-01

Risk for premature osteoporosis is a major health concern in astronauts and cosmonauts; the reversibility of the bone lost at the weight-bearing bone sites is not established, although it is suspected to take longer than the mission length. The bone three-dimensional structure and strength that could be uniquely affected by weightlessness is currently unknown. Our objective is to evaluate bone mass, microarchitecture, and strength of weight-bearing and non-weight-bearing bone in 13 cosmonauts before and for 12 months after a 4-month to 6-month sojourn in the International Space Station (ISS). Standard and advanced evaluations of trabecular and cortical parameters were performed using high-resolution peripheral quantitative computed tomography. In particular, cortical analyses involved determination of the largest common volume of each successive individual scan to improve the precision of cortical porosity and density measurements. Bone resorption and formation serum markers, and markers reflecting osteocyte activity or periosteal metabolism (sclerostin, periostin) were evaluated. At the tibia, in addition to decreased bone mineral densities at cortical and trabecular compartments, a 4% decrease in cortical thickness and a 15% increase in cortical porosity were observed at landing. Cortical size and density subsequently recovered and serum periostin changes were associated with cortical recovery during the year after landing. However, tibial cortical porosity or trabecular bone failed to recover, resulting in compromised strength. The radius, preserved at landing, unexpectedly developed postflight fragility, from 3 months post-landing onward, particularly in its cortical structure. Remodeling markers, uncoupled in favor of bone resorption at landing, returned to preflight values within 6 months, then declined farther to lower than preflight values. Our findings highlight the need for specific protective measures not only during, but also after spaceflight, because of continuing uncertainties regarding skeletal recovery long after landing. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Dyslipidemia and Diabetic Retinopathy

PubMed Central

Chang, Yo-Chen; Wu, Wen-Chuan

2013-01-01

Diabetic retinopathy (DR) is one of the major microvascular complications of diabetes. In developed countries, it is the most common cause of preventable blindness in diabetic adults. Dyslipidemia, a major systemic disorder, is one of the most important risk factors for cardiovascular disease. Patients with diabetes have an increased risk of suffering from dyslipidemia concurrently. The aim of this article is to review the association between diabetic retinopathy (DR) and traditional/nontraditional lipid markers, possible mechanisms involving lipid metabolism and diabetic retinopathy, and the effect of lipid-lowering therapies on diabetic retinopathy. For traditional lipid markers, evidence is available that total cholesterol and low-density lipoprotein cholesterol are associated with the presence of hard exudates in patients with DR. The study of nontraditional lipid markers is advancing only in recently years. The severity of DR is inversely associated with apolipoprotein A1 (ApoA1), whereas ApoB and the ApoB-to-ApoA1 ratio are positively associated with DR. The role of lipid-lowering medication is to work as adjunctive therapy for better control of diabetes-related complications including DR. PMID:24380088

Saturation of an Intra-Gene Pool Linkage Map: Towards a Unified Consensus Linkage Map for Fine Mapping and Synteny Analysis in Common Bean

PubMed Central

Galeano, Carlos H.; Fernandez, Andrea C.; Franco-Herrera, Natalia; Cichy, Karen A.; McClean, Phillip E.; Vanderleyden, Jos; Blair, Matthew W.

2011-01-01

Map-based cloning and fine mapping to find genes of interest and marker assisted selection (MAS) requires good genetic maps with reproducible markers. In this study, we saturated the linkage map of the intra-gene pool population of common bean DOR364×BAT477 (DB) by evaluating 2,706 molecular markers including SSR, SNP, and gene-based markers. On average the polymorphism rate was 7.7% due to the narrow genetic base between the parents. The DB linkage map consisted of 291 markers with a total map length of 1,788 cM. A consensus map was built using the core mapping populations derived from inter-gene pool crosses: DOR364×G19833 (DG) and BAT93×JALO EEP558 (BJ). The consensus map consisted of a total of 1,010 markers mapped, with a total map length of 2,041 cM across 11 linkage groups. On average, each linkage group on the consensus map contained 91 markers of which 83% were single copy markers. Finally, a synteny analysis was carried out using our highly saturated consensus maps compared with the soybean pseudo-chromosome assembly. A total of 772 marker sequences were compared with the soybean genome. A total of 44 syntenic blocks were identified. The linkage group Pv6 presented the most diverse pattern of synteny with seven syntenic blocks, and Pv9 showed the most consistent relations with soybean with just two syntenic blocks. Additionally, a co-linear analysis using common bean transcript map information against soybean coding sequences (CDS) revealed the relationship with 787 soybean genes. The common bean consensus map has allowed us to map a larger number of markers, to obtain a more complete coverage of the common bean genome. Our results, combined with synteny relationships provide tools to increase marker density in selected genomic regions to identify closely linked polymorphic markers for indirect selection, fine mapping or for positional cloning. PMID:22174773

Construction of High-Density Genetic Linkage Maps and Mapping of Growth-Related Quantitative Trail Loci in the Japanese Flounder (Paralichthys olivaceus)

PubMed Central

Niu, Yuze; Gao, Fengtao; Zhao, Yongwei; Zhang, Jing; Sun, Jian; Shao, Changwei; Liao, Xiaolin; Wang, Lei; Tian, Yongsheng; Chen, Songlin

2012-01-01

High-density genetic linkage maps were constructed for the Japanese flounder (Paralichthys olivaceus). A total of 1624 microsatellite markers were polymorphic in the reference family. Linkage analysis using JoinMap 4.0 resulted in the mapping of 1487 markers to 24 linkage groups, a result which was consistent with the 24 chromosomes seen in chromosome spreads. The female map was composed of 1257 markers, covering a total of 1663.8 cM with an average interval 1.35 cM between markers. The male map consisted of 1224 markers, spanning 1726.5 cM, with an average interval of 1.44 cM. The genome length in the Japanese flounder was estimated to be 1730.3 cM for the females and 1798.0 cM for the males, a coverage of 96.2% for the female and 96.0% for the male map. The mean recombination at common intervals throughout the genome revealed a slight difference between sexes, i.e. 1.07 times higher in the male than female. High-density genetic linkage maps are very useful for marker-assisted selection (MAS) programs for economically valuable traits in this species and for further evolutionary studies in flatfish and vertebrate species. Furthermore, four quantiative trait loci (QTL) associated with growth traits were mapped on the genetic map. One QTL was identified for body weight on LG 14 f, which explained 14.85% of the total variation of the body weight. Three QTL were identified for body width on LG14f and LG14m, accounting for 16.75%, 13.62% and 13.65% of the total variation in body width, respectively. The additive effects were evident as negative values. There were four QTL for growth traits clustered on LG14, which should prove to be very useful for improving growth traits using molecular MAS. PMID:23209734

Relationships between immunophenotype, Ki-67 index, microvascular density, Ep-CAM/P-cadherin, and MMP-2 expression in early-stage invasive ductal breast cancer.

PubMed

Niemiec, Joanna A; Adamczyk, Agnieszka; Małecki, Krzysztof; Majchrzyk, Kaja; Ryś, Janusz

2012-12-01

There is still a lack of complete consensus on immunohistochemical surrogate markers for luminal A (LA) and luminal B (LB), HER2, and basal-like subtypes of breast carcinomas and their correlation with cancer cell adhesion and invasion-promoting factors. Therefore, early-stage invasive ductal breast cancer patients (N=209) were recruited to the study and divided into 4 subtypes, on the basis of the expression of the estrogen/progesterone receptor and HER2 (LA: 74.4% of cases; LB: 7.8%; HER2: 5.6%; and triple-negative phenotype: 12.2%). Regardless of the above-mentioned classification, we divided all carcinomas into 2 groups: carcinomas expressing at least 1 basal marker [cytokeratine (CK)5/6, CK5, vimentin, epidermal growth factor receptor, or aberrant CK8/18 expression-membranous or in <10% of cells] versus carcinomas negative for basal markers. Then we studied the relationships between the above subtypes (2 classifications) and (i) the expression of adhesion molecules (Ep-CAM, P-cadherin), (ii) matrix metalloproteinases (MMP)-2, (iii) the proliferation index (MIB-1 LI), and (iv) the microvascular density. We confirmed that triple-negative phenotypes are characterized by basal marker expression, a high tumor grade, and high MIB-1 LI. In this subtype, we found MMP-2 expression in stromal leukocytes less frequently. Both LA carcinomas and carcinomas negative for basal markers were more often negative for epithelial cell adhesion molecule (Ep-CAM) and P-cadherin. Moreover, we noted a higher mean value of microvascular density in CK5/6 and Ep-CAM-immunopositive tumors, carcinomas with aberrant CK8/18 expression, and carcinomas with no or strong expression of MMP-2 in stromal fibroblast-like cells. These results might suggest that mechanisms of stroma remodeling and carcinogenesis (Ep-CAM is the suggested marker of breast progenitors) may differ between breast cancer subtypes.

Development of a 63K SNP Array for Cotton and High-Density Mapping of Intraspecific and Interspecific Populations of Gossypium spp.

PubMed Central

Hulse-Kemp, Amanda M.; Lemm, Jana; Plieske, Joerg; Ashrafi, Hamid; Buyyarapu, Ramesh; Fang, David D.; Frelichowski, James; Giband, Marc; Hague, Steve; Hinze, Lori L.; Kochan, Kelli J.; Riggs, Penny K.; Scheffler, Jodi A.; Udall, Joshua A.; Ulloa, Mauricio; Wang, Shirley S.; Zhu, Qian-Hao; Bag, Sumit K.; Bhardwaj, Archana; Burke, John J.; Byers, Robert L.; Claverie, Michel; Gore, Michael A.; Harker, David B.; Islam, Md S.; Jenkins, Johnie N.; Jones, Don C.; Lacape, Jean-Marc; Llewellyn, Danny J.; Percy, Richard G.; Pepper, Alan E.; Poland, Jesse A.; Mohan Rai, Krishan; Sawant, Samir V.; Singh, Sunil Kumar; Spriggs, Andrew; Taylor, Jen M.; Wang, Fei; Yourstone, Scott M.; Zheng, Xiuting; Lawley, Cindy T.; Ganal, Martin W.; Van Deynze, Allen; Wilson, Iain W.; Stelly, David M.

2015-01-01

High-throughput genotyping arrays provide a standardized resource for plant breeding communities that are useful for a breadth of applications including high-density genetic mapping, genome-wide association studies (GWAS), genomic selection (GS), complex trait dissection, and studying patterns of genomic diversity among cultivars and wild accessions. We have developed the CottonSNP63K, an Illumina Infinium array containing assays for 45,104 putative intraspecific single nucleotide polymorphism (SNP) markers for use within the cultivated cotton species Gossypium hirsutum L. and 17,954 putative interspecific SNP markers for use with crosses of other cotton species with G. hirsutum. The SNPs on the array were developed from 13 different discovery sets that represent a diverse range of G. hirsutum germplasm and five other species: G. barbadense L., G. tomentosum Nuttal × Seemann, G. mustelinum Miers × Watt, G. armourianum Kearny, and G. longicalyx J.B. Hutchinson and Lee. The array was validated with 1,156 samples to generate cluster positions to facilitate automated analysis of 38,822 polymorphic markers. Two high-density genetic maps containing a total of 22,829 SNPs were generated for two F2 mapping populations, one intraspecific and one interspecific, and 3,533 SNP markers were co-occurring in both maps. The produced intraspecific genetic map is the first saturated map that associates into 26 linkage groups corresponding to the number of cotton chromosomes for a cross between two G. hirsutum lines. The linkage maps were shown to have high levels of collinearity to the JGI G. raimondii Ulbrich reference genome sequence. The CottonSNP63K array, cluster file and associated marker sequences constitute a major new resource for the global cotton research community. PMID:25908569

Characterizing the marker-dye correction for Gafchromic(®) EBT2 film: a comparison of three analysis methods.

PubMed

McCaw, Travis J; Micka, John A; Dewerd, Larry A

2011-10-01

Gafchromic(®) EBT2 film has a yellow marker dye incorporated into the active layer of the film that can be used to correct the film response for small variations in thickness. This work characterizes the effect of the marker-dye correction on the uniformity and uncertainty of dose measurements with EBT2 film. The effect of variations in time postexposure on the uniformity of EBT2 is also investigated. EBT2 films were used to measure the flatness of a (60)Co field to provide a high-spatial resolution evaluation of the film uniformity. As a reference, the flatness of the (60)Co field was also measured with Kodak EDR2 films. The EBT2 films were digitized with a flatbed document scanner 24, 48, and 72 h postexposure, and the images were analyzed using three methods: (1) the manufacturer-recommended marker-dye correction, (2) an in-house marker-dye correction, and (3) a net optical density (OD) measurement in the red color channel. The field flatness was calculated from orthogonal profiles through the center of the field using each analysis method, and the results were compared with the EDR2 measurements. Uncertainty was propagated through a dose calculation for each analysis method. The change in the measured field flatness for increasing times postexposure was also determined. Both marker-dye correction methods improved the field flatness measured with EBT2 film relative to the net OD method, with a maximum improvement of 1% using the manufacturer-recommended correction. However, the manufacturer-recommended correction also resulted in a dose uncertainty an order of magnitude greater than the other two methods. The in-house marker-dye correction lowered the dose uncertainty relative to the net OD method. The measured field flatness did not exhibit any unidirectional change with increasing time postexposure and showed a maximum change of 0.3%. The marker dye in EBT2 can be used to improve the response uniformity of the film. Depending on the film analysis method used, however, application of a marker-dye correction can improve or degrade the dose uncertainty relative to the net OD method. The uniformity of EBT2 was found to be independent of the time postexposure.

Altered Right Ventricular Kinetic Energy Work Density and Viscous Energy Dissipation in Patients with Pulmonary Arterial Hypertension: A Pilot Study Using 4D Flow MRI.

PubMed

Han, Q Joyce; Witschey, Walter R T; Fang-Yen, Christopher M; Arkles, Jeffrey S; Barker, Alex J; Forfia, Paul R; Han, Yuchi

2015-01-01

Right ventricular (RV) function has increasingly being recognized as an important predictor for morbidity and mortality in patients with pulmonary arterial hypertension (PAH). The increased RV after-load increase RV work in PAH. We used time-resolved 3D phase contrast MRI (4D flow MRI) to derive RV kinetic energy (KE) work density and energy loss in the pulmonary artery (PA) to better characterize RV work in PAH patients. 4D flow and standard cardiac cine images were obtained in ten functional class I/II patients with PAH and nine healthy subjects. For each individual, we calculated the RV KE work density and the amount of viscous dissipation in the PA. PAH patients had alterations in flow patterns in both the RV and the PA compared to healthy subjects. PAH subjects had significantly higher RV KE work density than healthy subjects (94.7±33.7 mJ/mL vs. 61.7±14.8 mJ/mL, p = 0.007) as well as a much greater percent PA energy loss (21.1±6.4% vs. 2.2±1.3%, p = 0.0001) throughout the cardiac cycle. RV KE work density and percent PA energy loss had mild and moderate correlations with RV ejection fraction. This study has quantified two kinetic energy metrics to assess RV function using 4D flow. RV KE work density and PA viscous energy loss not only distinguished healthy subjects from patients, but also provided distinction amongst PAH patients. These metrics hold promise as imaging markers for RV function.

Biological markers of melancholia and reclassification of depressive disorders.

PubMed

Greden, J F

1982-01-01

Pathophysiological markers of melancholia are being developed in four major areas: 1) neuroendocrine; 2) sleep; 3) psychomotor and 4) biochemical. Neuroendocrine markers include a failure of suppress plasma cortisol secretion in the dexamethasone suppression test (DST), diminished thyrotrophin (TSH) response to thyrotrophin releasing hormone (TRH stimulation test), and blunted growth hormone response to a variety of stimulating agents such as d-amphetamine, methylamphetamine, clonidine, L-dopa and insulin (growth hormone test). Of these, the DST is the best standardized. It is a highly specific laboratory marker with documented value in diagnosis, assessing prognosis and monitoring treatment progress. Sleep EEG abnormalities include reduced REM latency, increased REM density, reduction in delta sleep and impaired sleep efficiency. Sleep EEGs are pragmatically difficult, but results are quite specific. Elongated speech pause time (SPT) during "automatic speech" is a promising marker of psychomotor regulation. This simple, non-invasive measure may have special value in reducing clinical subjectivity and in monitoring treatment progress. Biochemical markers include: 1) platelet monoamine oxidase (MAO) activity; 2) in vitro lithium RBC transport and 3) urinary MHPG levels. Standardizations of biochemical tests are still lacking. Most biological tests for melancholia operate by indirectly "marking" CNS limbic system dysfunction. For wide acceptance, a test must be safe, moderately sensitive, highly specific, practical, relatively inexpensive and not significantly altered by common anti-depressant treatments. The DST best meets these criteria at this time. Proper utilization of test results requires knowledge of baseline prevalence rates and of the concepts of sensitivity (true-positive rate), specificity (true negative rate) and positive and negative predictive values (diagnostic confidence). No single marker will meet all clinical needs. Combinations or serial use of tests will hopefully enhance their already considerable usefulness.

Response learning stimulates dendritic spine growth on dorsal striatal medium spiny neurons.

PubMed

Briones, Brandy A; Tang, Vincent D; Haye, Amanda E; Gould, Elizabeth

2018-06-23

Increases in the number and/or the size of dendritic spines, sites of excitatory synapses, have been linked to different types of learning as well as synaptic plasticity in several brain regions, including the hippocampus, sensory cortex, motor cortex, and cerebellum. By contrast, a previous study reported that training on a maze task requiring the dorsal striatum has no effect on medium spiny neuron dendritic spines in this area. These findings might suggest brain region-specific differences in levels of plasticity as well as different cellular processes underlying different types of learning. No previous studies have investigated whether dendritic spine density changes may be localized to specific subpopulations of medium spiny neurons, nor have they examined dendritic spines in rats trained on a dorsolateral striatum-dependent maze task in comparison to rats exposed to the same type of maze in the absence of training. To address these questions further, we labeled medium spiny neurons with the lipophilic dye DiI and stained for the protein product of immediate early gene zif 268, an indirect marker of neuronal activation, in both trained and untrained groups. We found a small but significant increase in dendritic spine density on medium spiny neurons of the dorsolateral striatum after short-term intensive training, along with robust increases in the density of spines with mushroom morphology coincident with reductions in the density of spines with thin morphology. However, these results were not associated with zif 268 expression. Our findings suggest that short-term intensive training on a dorsolateral striatum-dependent maze task induces rapid increases in dendritic spine density and maturation on medium spiny neurons of the dorsolateral striatum, an effect which may contribute to early acquisition of the learned response in maze training. Copyright © 2018. Published by Elsevier Inc.

Centella asiatica increases hippocampal synaptic density and improves memory and executive function in aged mice.

PubMed

Gray, Nora E; Zweig, Jonathan A; Caruso, Maya; Martin, Marjoen D; Zhu, Jennifer Y; Quinn, Joseph F; Soumyanath, Amala

2018-06-19

Centella asiatica is a plant used for centuries to enhance memory. We have previously shown that a water extract of Centella asiatica (CAW) attenuates age-related spatial memory deficits in mice and improves neuronal health. Yet the effect of CAW on other cognitive domains remains unexplored as does its mechanism of improving age-related cognitive impairment. This study investigates the effects of CAW on a variety of cognitive tasks as well as on synaptic density and mitochondrial and antioxidant pathways. Twenty-month-old CB6F1 mice were treated with CAW (2 mg/ml) in their drinking water for 2 weeks prior to behavioral testing. Learning, memory, and executive function were assessed using the novel object recognition task (NORT), object location memory task (OLM), and odor discrimination reversal learning (ODRL) test. Tissue was collected for Golgi analysis of spine density as well as assessment of mitochondrial, antioxidant, and synaptic proteins. CAW improved performance in all behavioral tests suggesting effects on hippocampal and cortical dependent memory as well as on prefrontal cortex mediated executive function. There was also an increase in synaptic density in the treated animals, which was accompanied by increased expression of the antioxidant response gene NRF2 as well as the mitochondrial marker porin. These data show that CAW can increase synaptic density as well as antioxidant and mitochondrial proteins and improve multiple facets of age-related cognitive impairment. Because mitochondrial dysfunction and oxidative stress also accompany cognitive impairment in many pathological conditions this suggests a broad therapeutic utility of CAW. © 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

Sclerostin Levels and Bone Turnover Markers in Adolescents with Anorexia Nervosa and Healthy Adolescent Girls

PubMed Central

Faje, Alexander T.; Fazeli, Pouneh K.; Katzman, Debra K.; Miller, Karen K.; Breggia, Anne; Rosen, Clifford J.; Mendes, Nara; Klibanski, Anne; Misra, Madhusmita

2012-01-01

Sclerostin, product of the SOST gene, is an important determinant of bone formation and resorption. Adolescents with anorexia nervosa (AN) have low bone density and decreased levels of bone turnover markers. However, sclerostin has not been examined in AN as a potential mediator of impaired bone metabolism. Our study objectives were to (i) assess associations of sclerostin with surrogate bone turnover markers in girls with AN and controls and (ii) examine effects of transdermal estradiol on sclerostin in AN. 69 girls (44 with AN and 25 normal-weight controls) 13–18 years old were studied at baseline. 22 AN girls were randomized to transdermal estradiol (plus cyclic medroxyprogesterone) or placebo in a double-blind study for 12 months. Sclerostin correlated positively with P1NP and CTX in controls (r = 0. 67 and 0. 53, p = 0. 0002 and 0. 005, respectively) but not in AN despite comparable levels at baseline. Changes in sclerostin over twelve months did not differ in girls randomized to estradiol or placebo. The relationship between sclerostin and bone turnover markers is disrupted in adolescent girls with AN. Despite an increase in BMD with estradiol administration in AN, estrogen does not impact sclerostin levels in this group. PMID:22728230

Diabetes, Biochemical Markers of Bone Turnover, Diabetes Control, and Bone

PubMed Central

Starup-Linde, Jakob

2012-01-01

Diabetes mellitus is known to have late complications including micro vascular and macro vascular disease. This review focuses on another possible area of complication regarding diabetes; bone. Diabetes may affect bone via bone structure, bone density, and biochemical markers of bone turnover. The aim of the present review is to examine in vivo from humans on biochemical markers of bone turnover in diabetics compared to non-diabetics. Furthermore, the effect of glycemic control on bone markers and the similarities and differences of type 1- and type 2-diabetics regarding bone markers will be evaluated. A systematic literature search was conducted using PubMed, Embase, Cinahl, and SveMed+ with the search terms: “Diabetes mellitus,” “Diabetes mellitus type 1,” “Insulin dependent diabetes mellitus,” “Diabetes mellitus type 2,” “Non-insulin dependent diabetes mellitus,” “Bone,” “Bone and Bones,” “Bone diseases,” “Bone turnover,” “Hemoglobin A Glycosylated,” and “HbA1C.” After removing duplicates from this search 1,188 records were screened by title and abstract and 75 records were assessed by full text for inclusion in the review. In the end 43 records were chosen. Bone formation and resorption markers are investigated as well as bone regulating systems. T1D is found to have lower osteocalcin and CTX, while osteocalcin and tartrate-resistant acid are found to be lower in T2D, and sclerostin is increased and collagen turnover markers altered. Other bone turnover markers do not seem to be altered in T1D or T2D. A major problem is the lack of histomorphometric studies in humans linking changes in turnover markers to actual changes in bone turnover and further research is needed to strengthen this link. PMID:23482417

Individualized therapy to prevent bone mineral density loss after kidney and kidney-pancreas transplantation.

PubMed

Mainra, Rahul; Elder, Grahame J

2010-01-01

Most patients who undergo kidney or kidney-pancreas transplantation have renal osteodystrophy, and immediately after transplantation bone mineral density (BMD) commonly falls. Together, these abnormalities predispose to an increased fracture incidence. Bisphosphonate or calcitriol therapy can preserve BMD after transplantation, but although bisphosphonates may be more effective, they pose potential risks for adynamic bone. A total of 153 kidney (61%) and kidney-pancreas (39%) transplant recipients were allocated to bisphosphonate (62%) or calcitriol (38%) therapy using an algorithm that incorporated BMD, prevalent vertebral fracture, biomarkers of bone turnover, and risk factor assessment. Patients received cholecalciferol and calcium as appropriate and were followed for 12 mo. Patients who were treated with bisphosphonates had lower BMD at the lumbar spine and femoral neck and longer time on dialysis. Age and gender were similar between the groups. At 12 mo, bisphosphonate-treated patients had significant BMD increases at the lumber spine and femoral neck and a negative trend at the wrist. Patients who were allocated to calcitriol, who were assessed to have lower baseline fracture risk, had no significant change in BMD at any site. At 1 yr, mean levels of bone turnover marker and intact parathyroid hormone normalized in both groups. Incident fracture rates did not differ significantly. With targeted treatment, BMD levels were stable or improved and bone turnover markers normalized. This algorithm provides a guide to targeting therapy after transplantation that avoids BMD loss and may reduce suppression of bone turnover.

Indocyanine green-mediated photobiomodulation on human osteoblast cells.

PubMed

Ateş, Gamze Bölükbaşı; Ak, Ayşe; Garipcan, Bora; Gülsoy, Murat

2018-05-09

Photobiomodulation (PBM) and photodynamic therapy (PDT) share similar mechanisms but have opposite aims. Increased levels of reactive oxygen species (ROS) in the target tissue in response to light combined photosensitizer (PS) application may lead to cell proliferation or oxidative damage depending on the ROS amount. The purpose of the present study is to investigate the effect of indocyanine green (ICG)-mediated PBM on osteoblast cells by measuring cell viability, proliferation, alkaline phosphatase (ALP) activity, mineralization, and gene expressions of three phenotypic osteoblast markers. A diode laser irradiating at 809 nm (10 W output power, 50 mW/cm 2 power density) was used at 0.5, 1, and 2 J/cm 2 energy densities (10, 20, and 40 s respectively) was applied following ICG incubation. No inhibitory effect was observed in cell viability and proliferation according to the (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and Alamar Blue assays. ICG-mediated PBM did not alter cell viability but increased ALP activity and enhanced mineralization of existing osteoblasts. These results were also confirmed by real-time polymerase chain reaction (RT-PCR) analysis of osteoblastic markers. PS can be combined to PBM not only to damage the malignant cells as aimed in PDT studies, but also to promote cellular activity. The findings of this in vitro study may contribute to in vivo studies and ICG-mediated PBM can have promising outcomes in bone healing and regeneration therapies in future.

Significant increase in IgG4+ plasma cells in gastric biopsy specimens from patients with pernicious anaemia.

PubMed

Bedeir, Ahmed S; Lash, Richard H; Lash, Jonathan G; Ray, Mukunda B

2010-11-01

To investigate the presence of IgG4+ plasma cells in gastric mucosal biopsy samples from patients with atrophic gastritis (AG) and a history of pernicious anaemia (PA) (AG+PA+). Gastric mucosal biopsy specimens from 46 patients with AG+PA+ were investigated. As controls, we evaluated specimens from patients with AG but no history of PA (AG+ PA-) (n=25), normal histology (n=25), mild chronic inactive gastritis (MCIG) (n=25) or Helicobacter pylori gastritis (HP) (n=25). IgG4+ plasma cells were detected by two immunohistochemical methods: (1) using a monoclonal antibody, the average of the three most cellular high-power fields was counted in areas with the highest density of IgG4+ plasma cells; (2) using a dual-chromagen stain for both IgG4 and CD138 (plasma cell marker), the number of IgG4+ cells per 200 CD138+ plasma cells was counted. The latter was used to ensure that the number of IgG4+ cells was not simply related to the degree of inflammation (density of plasma cells). Identical results were obtained with the two staining methods. Increased numbers of IgG4+ plasma cells were present in 37% of patients with AG+PA+, but in none with AG+PA-, MCIG, HP or normal gastric biopsy results (100% specific, p=0.0001). IgG4+ plasma cells may play a role in the pathogenesis of PA and may be a useful marker for its diagnosis.

Apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy.

PubMed

Zhang, Li; Takara, Kazuhiro; Yamakawa, Daishi; Kidoya, Hiroyasu; Takakura, Nobuyuki

2016-01-01

Antiangiogenic agents transiently normalize tumor vessel structure and improve vessel function, thereby providing a window of opportunity for enhancing the efficacy of chemotherapy or radiotherapy. Currently, there are no reliable predictors or markers reflecting this vessel normalization window during antiangiogenic therapy. Apelin, the expression of which is regulated by hypoxia, and which has well-described roles in tumor progression, is an easily measured secreted protein. Here, we show that apelin can be used as a marker for the vessel normalization window during antiangiogenic therapy. Mice bearing s.c. tumors resulting from inoculation of the colon adenocarcinoma cell line HT29 were treated with a single injection of bevacizumab, a mAb neutralizing vascular endothelial growth factor. Tumor growth, vessel density, pericyte coverage, tumor hypoxia, and small molecule delivery were determined at four different times after treatment with bevacizumab (days 1, 3, 5, and 8). Tumor growth and vessel density were significantly reduced after bevacizumab treatment, which also significantly increased tumor vessel maturity, and improved tumor hypoxia and small molecule delivery between days 3 and 5. These effects abated by day 8, suggesting that a time window for vessel normalization was opened between days 3 and 5 during bevacizumab treatment in this model. Apelin mRNA expression and plasma apelin levels decreased transiently at day 5 post-treatment, coinciding with vessel normalization. Thus, apelin is a potential indicator of the vessel normalization window during antiangiogenic therapy. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Work-Family Life Courses and Metabolic Markers in the MRC National Survey of Health and Development.

PubMed

Lacey, Rebecca E; Kumari, Meena; Sacker, Amanda; Stafford, Mai; Kuh, Diana; McMunn, Anne

2016-01-01

The aim was to investigate whether the combined work-family life courses of British men and women were associated with differences in metabolic markers-waist circumference, blood pressure, high density lipoprotein cholesterol, triglycerides, and glycated haemoglobin-in mid-life. We used data from the Medical Research Council's National Survey of Health and Development-the 1946 British birth cohort. Multi-channel sequence analysis was used to create a typology of eight work-family life course types combining information on work, partnerships and parenthood between ages 16-51. Linear regression tested associations between work-family types and metabolic outcomes at age 53 on multiply imputed data (20 imputations) of >2,400 participants. Compared with men with strong ties to employment and early transitions to family life, men who made later transitions to parenthood and maintained strong ties to paid work had smaller waist circumferences (-2.16cm, 95% CI: -3.73, -0.59), lower triglycerides (9.78% lower, 95% CI: 0.81, 17.94) and lower blood pressure (systolic: -4.03mmHg, 95% CI: -6.93, -1.13; diastolic: -2.34mmHg, 95% CI: -4.15, -0.53). Married men and women who didn't have children had increased high density lipoprotein cholesterol (7.23% higher, 95% CI: 0.68, 14.21) and lower waist circumferences (-4.67cm, 95% CI: -8.37, -0.97), respectively. For men later transitions to parenthood combined with strong ties to paid work were linked to reduced metabolic risk in mid-life. Fewer differences between work-family types and metabolic markers were seen for women.

Plasmodium falciparum exhibits markers of regulated cell death at high population density in vitro.

PubMed

Engelbrecht, Dewaldt; Coetzer, Thérèsa Louise

2016-12-01

The asexual erythrocytic cycle of the protozoan parasite Plasmodium falciparum is responsible for the pathogenesis of malaria and causes the overwhelming majority of malaria deaths. Rapidly increasing parasitaemia during this 48hour cycle threatens the survival of the human host and the parasite prior to transmission of the slow-maturing sexual stages to the mosquito host. The parasite may utilise regulated cell death (RCD) to control the burden of infection on the host and thus aid its own survival and transmission. The occurrence of RCD in P. falciparum remains a controversial topic. We provide strong evidence for the occurrence of an apoptosis-like phenotype of RCD in P. falciparum under conditions of high parasite density. P. falciparum was maintained in vitro and stressed by allowing growth to an unrestricted peak parasitaemia. Cell death markers, including morphological changes, DNA fragmentation, mitochondrial polarisation and phosphatidylserine externalisation were used to characterise parasite death at the time of peak parasitaemia and 24h later. At peak parasitaemia, mitochondrial depolarisation was observed, together with phosphatidylserine externalisation in both parasitised- and neighbouring non-infected erythrocytes. DNA fragmentation coincided with a decline in parasitaemia. Fewer merozoites were observed in mature schizonts at peak parasitaemia. Growth recovery to near-peak parasitaemia was noted within two intraerythrocytic cycles. The combination and chronological order of the biochemical markers of cell death suggest the occurrence of an apoptosis-like phenotype. The identification of a RCD pathway in P. falciparum may provide novel drug targets, particularly if the pathway differs from the host machinery. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Increased Lymphatic Vessel Length Is Associated With the Fibroblast Reticulum and Disease Severity in Usual Interstitial Pneumonia and Nonspecific Interstitial Pneumonia

PubMed Central

Cosgrove, Gregory P.; Janssen, William J.; Huie, Tristan J.; Burnham, Ellen L.; Heinz, David E.; Curran-Everett, Douglas; Sahin, Hakan; Schwarz, Marvin I.; Cool, Carlyne D.; Groshong, Steve D.; Geraci, Mark W.; Tuder, Rubin M.; Hyde, Dallas M.; Henson, Peter M.

2012-01-01

Background: Lymphangiogenesis responds to tissue injury as a key component of normal wound healing. The development of fibrosis in the idiopathic interstitial pneumonias may result from abnormal wound healing in response to injury. We hypothesize that increased lymphatic vessel (LV) length, a marker of lymphangiogenesis, is associated with parenchymal components of the fibroblast reticulum (organizing collagen, fibrotic collagen, and fibroblast foci), and its extent correlates with disease severity. Methods: We assessed stereologically the parenchymal structure of fibrotic lungs and its associated lymphatic network, which was highlighted immunohistochemically in age-matched samples of usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP) with FVC < 80%, COPD with a Global Initiative for Obstructive Lung Disease stage 0, and normal control lungs. Results: LV length density, as opposed to vessel volume density, was found to be associated with organizing and fibrotic collagen density (P < .0001). Length density of LVs and the volume density of organizing and fibrotic collagen were significantly associated with severity of both % FVC (P < .001) and diffusing capacity of the lung for carbon monoxide (P < .001). Conclusions: Severity of disease in UIP and NSIP is associated with increased LV length and is strongly associated with components of the fibroblast reticulum, namely organizing and fibrotic collagen, which supports a pathogenic role of LVs in these two diseases. Furthermore, the absence of definable differences between UIP and NSIP suggests that LVs are a unifying mechanism for the development of fibrosis in these fibrotic lung diseases. PMID:22797508

A general model for likelihood computations of genetic marker data accounting for linkage, linkage disequilibrium, and mutations.

PubMed

Kling, Daniel; Tillmar, Andreas; Egeland, Thore; Mostad, Petter

2015-09-01

Several applications necessitate an unbiased determination of relatedness, be it in linkage or association studies or in a forensic setting. An appropriate model to compute the joint probability of some genetic data for a set of persons given some hypothesis about the pedigree structure is then required. The increasing number of markers available through high-density SNP microarray typing and NGS technologies intensifies the demand, where using a large number of markers may lead to biased results due to strong dependencies between closely located loci, both within pedigrees (linkage) and in the population (allelic association or linkage disequilibrium (LD)). We present a new general model, based on a Markov chain for inheritance patterns and another Markov chain for founder allele patterns, the latter allowing us to account for LD. We also demonstrate a specific implementation for X chromosomal markers that allows for computation of likelihoods based on hypotheses of alleged relationships and genetic marker data. The algorithm can simultaneously account for linkage, LD, and mutations. We demonstrate its feasibility using simulated examples. The algorithm is implemented in the software FamLinkX, providing a user-friendly GUI for Windows systems (FamLinkX, as well as further usage instructions, is freely available at www.famlink.se ). Our software provides the necessary means to solve cases where no previous implementation exists. In addition, the software has the possibility to perform simulations in order to further study the impact of linkage and LD on computed likelihoods for an arbitrary set of markers.

PB-1: The Relationship Between Anti Apoptotic Marker (BCL-2) and Biochemical Markers in Type 2 Diabetes Patients

PubMed Central

Damitri, TD; Faridah, AR; Imran, Y; Hasnan, J.

2006-01-01

Purpose : To investigate the expression of anti apoptotic marker (bcl-2) and the level of biochemical markers in type 2 diabetes patients. METHODS : A cross-sectional study was conducted from August 2003 to November 2005. Forty one type 2 diabetes patients and 36 non diabetes (control) subjects aged between 20 to 70 years were included in this study. Blood samples were collected for fasting plasma glucose (FPG), triglycerides (TG), Total cholesterol (TC), High density lipoprotein cholesterol (HDLC), Low density lipoprotein cholesterol (LDLC) and analyzed in the Chemical Pathology laboratory, while glycosylated hemoglobin A1c (A1C) was analyzed in the Endocrine laboratory. The skin biopsy tissue samples were stained with immunohistochemistry (IHC) stain for expression of bcl-2 in the Pathology laboratory. RESULTS : There was a significant difference (p<0.001) between both groups for mean FPG (diabetics=11.02±4.25, control=4.41±1.12 mmol/L), HDLC (diabetics=1.00±0.38, control=1.47±0.72 mmol/L) and A1C (diabetics=9.50±2.24%, control=5.00±0.67%). However, there was no significant difference for TG, TC, and LDLC between both groups. Interestingly, the difference of mean bcl-2 expression were very highly significant (p<0.001) when compared between both groups. Mean bcl-2 expression was dibetics= 1.88±0.33 and control= 1.47±0.51. Positive bcl-2 expression was found in only 5 (12.2%) diabetics while 36 (87.8%) diabetics showed negative expression. Positive bcl-2 expression was observed in 19 (52.8%) controls while 17 (47.2%) showed negative expression. CONCLUSION : The expression of anti apoptotic marker bcl-2 was increased in non diabetic subjects in order to prevent cell death. However, the reduced expression of bcl-2 in diabetic patients may be associated with programmed cell death. The detailed mechanism for the gene expression of bcl-2 may help us to understand how bcl-2 is involved in apoptosis in diabetic microvasculature complications.

SNP discovery by high-throughput sequencing in soybean

PubMed Central

2010-01-01

Background With the advance of new massively parallel genotyping technologies, quantitative trait loci (QTL) fine mapping and map-based cloning become more achievable in identifying genes for important and complex traits. Development of high-density genetic markers in the QTL regions of specific mapping populations is essential for fine-mapping and map-based cloning of economically important genes. Single nucleotide polymorphisms (SNPs) are the most abundant form of genetic variation existing between any diverse genotypes that are usually used for QTL mapping studies. The massively parallel sequencing technologies (Roche GS/454, Illumina GA/Solexa, and ABI/SOLiD), have been widely applied to identify genome-wide sequence variations. However, it is still remains unclear whether sequence data at a low sequencing depth are enough to detect the variations existing in any QTL regions of interest in a crop genome, and how to prepare sequencing samples for a complex genome such as soybean. Therefore, with the aims of identifying SNP markers in a cost effective way for fine-mapping several QTL regions, and testing the validation rate of the putative SNPs predicted with Solexa short sequence reads at a low sequencing depth, we evaluated a pooled DNA fragment reduced representation library and SNP detection methods applied to short read sequences generated by Solexa high-throughput sequencing technology. Results A total of 39,022 putative SNPs were identified by the Illumina/Solexa sequencing system using a reduced representation DNA library of two parental lines of a mapping population. The validation rates of these putative SNPs predicted with low and high stringency were 72% and 85%, respectively. One hundred sixty four SNP markers resulted from the validation of putative SNPs and have been selectively chosen to target a known QTL, thereby increasing the marker density of the targeted region to one marker per 42 K bp. Conclusions We have demonstrated how to quickly identify large numbers of SNPs for fine mapping of QTL regions by applying massively parallel sequencing combined with genome complexity reduction techniques. This SNP discovery approach is more efficient for targeting multiple QTL regions in a same genetic population, which can be applied to other crops. PMID:20701770

The green peach aphid Myzus persicae perform better on pre-infested Chinese cabbage Brassica pekinensis by enhancing host plant nutritional quality

PubMed Central

Cao, He-He; Liu, Hui-Ru; Zhang, Zhan-Feng; Liu, Tong-Xian

2016-01-01

The green peach aphid, Myzus persicae Sulzer, is a notorious pest on vegetables, which often aggregates in high densities on crop leaves. In this study, we investigated whether M. persicae could suppress the resistance level of Chinese cabbage Brassica pekinensis. M. persicae performed better in terms of weight gain (~33% increase) and population growth (~110% increase) when feeding on previously infested (pre-infested) Chinese cabbage compared with those on non-infested plants. However, when given a choice, 64% of the aphids preferred to settle on non-infested leaves, while 29% of aphids chose pre-infested leaves that had a 2.9 times higher concentration of glucosinolates. Aphid feeding significantly enhanced the amino acid:sugar ratio of phloem sap and the absolute amino acid concentration in plant leaves. Aphid infestation significantly increased the expression levels of salicylic acid (SA) marker genes, while it had marginal effects on the expression of jasmonate marker genes. Exogenously applied SA or methyl jasmonate had no significant effects on M. persicae performance, although these chemicals increased glucosinolates concentration in plant leaves. M. persicae infestation increase amino acid:sugar ratio and activate plant defenses, but aphid performed better on pre-infested plants, suggesting that both nutrition and toxics should be considered in insect-plant interaction. PMID:26905564

Melatonin Decreases Pulmonary Vascular Remodeling and Oxygen Sensitivity in Pulmonary Hypertensive Newborn Lambs

PubMed Central

Astorga, Cristian R.; González-Candia, Alejandro; Candia, Alejandro A.; Figueroa, Esteban G.; Cañas, Daniel; Ebensperger, Germán; Reyes, Roberto V.; Llanos, Aníbal J.; Herrera, Emilio A.

2018-01-01

Background: Chronic hypoxia and oxidative stress during gestation lead to pulmonary hypertension of the neonate (PHN), a condition characterized by abnormal pulmonary arterial reactivity and remodeling. Melatonin has strong antioxidant properties and improves pulmonary vascular function. Here, we aimed to study the effects of melatonin on the function and structure of pulmonary arteries from PHN lambs. Methods: Twelve lambs (Ovis aries) gestated and born at highlands (3,600 m) were instrumented with systemic and pulmonary catheters. Six of them were assigned to the control group (CN, oral vehicle) and 6 were treated with melatonin (MN, 1 mg.kg−1.d−1) during 10 days. At the end of treatment, we performed a graded oxygenation protocol to assess cardiopulmonary responses to inspired oxygen variations. Further, we obtained lung and pulmonary trunk samples for histology, molecular biology, and immunohistochemistry determinations. Results: Melatonin reduced the in vivo pulmonary pressor response to oxygenation changes. In addition, melatonin decreased cellular density of the media and diminished the proliferation marker KI67 in resistance vessels and pulmonary trunk (p < 0.05). This was associated with a decreased in the remodeling markers α-actin (CN 1.28 ± 0.18 vs. MN 0.77 ± 0.04, p < 0.05) and smoothelin-B (CN 2.13 ± 0.31 vs. MN 0.88 ± 0.27, p < 0.05). Further, melatonin increased vascular density by 134% and vascular luminal surface by 173% (p < 0.05). Finally, melatonin decreased nitrotyrosine, an oxidative stress marker, in small pulmonary vessels (CN 5.12 ± 0.84 vs. MN 1.14 ± 0.34, p < 0.05). Conclusion: Postnatal administration of melatonin blunts the cardiopulmonary response to hypoxia, reduces the pathological vascular remodeling, and increases angiogenesis in pulmonary hypertensive neonatal lambs.These effects improve the pulmonary vascular structure and function in the neonatal period under chronic hypoxia. PMID:29559926

A single dose of trichloroethylene given during development does not substantially alter markers of neuroinflammation in brains of adult mice.

PubMed

Meadows, Jacqueline R; Parker, Chevonne; Gilbert, Kathleen M; Blossom, Sarah J; DeWitt, Jamie C

2017-12-01

Trichloroethylene (TCE) is a widespread environmental contaminant associated with developmental immunotoxicity and neurotoxicity. Previous studies have shown that MRL +/+ mice exposed to TCE from gestation through early-life demonstrate robust increases in inflammatory markers in peripheral CD4 + T-cells, as well as glutathione depletion and increased oxidative stress in cerebellum-associated with alterations in behavior. Since increased oxidative stress is associated with neuroinflammation, we hypothesized that neuroinflammatory markers could be altered relative to unexposed mice. MRL +/+ mice were given 0.5 mg/ml of TCE in vehicle or vehicle (water with 1% Alkamuls EL-620) from conception through early adulthood via drinking water to dams and then directly to post-weaning offspring. Animals were euthanized at 49 days of age and levels of pro- and anti-inflammatory cytokines, density of T-cell staining, and micro-glial morphology were evaluated in brains to begin to ascertain a neuroinflammatory profile. Levels of IL-6 were decreased in female animals and while not statistically significant, and levels of IL-10 were higher in brains of exposed male and female animals. Supportive of this observation, although not statistically significant, the number of ameboid microglia was higher in exposed relative to unexposed animals. This overall profile suggests the emergence of an anti-inflammatory/neuroprotective phenotype in exposed animals, possibly as a compensatory response to neuroinflammation that is known to be induced by developmental exposure to TCE.

Denosumab in Postmenopausal Osteoporosis: What the Clinician Needs to Know

PubMed Central

Lewiecki, E. Michael

2009-01-01

Denosumab is a subcutaneously (SC) administered investigational fully human monoclonal antibody to receptor activator of nuclear factor-kB ligand (RANKL), a cytokine member of the tumor necrosis factor family that is the principal mediator of osteoclastic bone resorption. RANKL stimulates the formation, activity, and survival of osteoclasts, and is implicated in the pathogenesis of postmenopausal osteoporosis and other skeletal disorders associated with increased bone remodeling. Denosumab binds RANKL, preventing it from binding to RANK, thereby reducing the formation, activity, and survival of osteoclasts and slowing the rate of bone resorption. Postmenopausal women with low bone mineral density (BMD) treated with denosumab have a reduction of bone turnover markers and an increase in BMD that is rapid, sustained, and reversible. In postmenopausal women with osteoporosis, denosumab reduces the risk of vertebral, hip, and nonvertebral fractures. In postmenopausal women with low BMD randomized to receive denosumab or alendronate, denosumab is associated with a significantly greater increase in BMD and further reduction in bone turnover markers compared with alendronate. In postmenopausal women with low BMD who were previously treated with alendronate, those who switched to denosumab have a significantly greater BMD increase and further reduction in bone turnover markers compared with those continuing alendronate. Denosumab is well tolerated with a favorable safety profile. It is a promising emerging drug for the prevention and treatment of osteoporosis, offering a long dosing interval of every 6 months and convenient SC dosing, with the potential of improving long-term adherence to therapy compared with current oral treatments. PMID:22870424

Characterization of polyploid wheat genomic diversity using a high-density 90 000 single nucleotide polymorphism array

USDA-ARS?s Scientific Manuscript database

High-density single nucleotide polymorphism (SNP) genotyping chips are a powerful tool for studying genomic patterns of diversity, inferring ancestral relationships among individuals in populations and studying marker-trait associations in mapping experiments. We developed a genotyping array includ...

Microsatellite DNA in genomic survey sequences and UniGenes of loblolly pine

Treesearch

Craig S Echt; Surya Saha; Dennis L Deemer; C Dana Nelson

2011-01-01

Genomic DNA sequence databases are a potential and growing resource for simple sequence repeat (SSR) marker development in loblolly pine (Pinus taeda L.). Loblolly pine also has many expressed sequence tags (ESTs) available for microsatellite (SSR) marker development. We compared loblolly pine SSR densities in genome survey sequences (GSSs) to those in non-redundant...

Structure-function relationships in the stem cell's mechanical world A: seeding protocols as a means to control shape and fate of live stem cells.

PubMed

Zimmermann, Joshua A; Knothe Tate, Melissa L

2011-12-01

Shape and fate are intrinsic manifestations of form and function at the cell scale. Here we hypothesize that seeding density and protocol affect the form and function of live embryonic murine mesenchymal stem cells (MSCs) and their nuclei. First, the imperative for study of live cells was demonstrated in studies showing changes in cell nucleus shape that were attributable to fixation per se. Hence, we compared live cell and nuclear volume and shape between groups of a model MSC line (C3H10T1/2) seeded at, or proliferated from 5,000 cells/cm2 to one of three target densities to achieve targeted development contexts. Cell volume was shown to be dependent on initial seeding density whereas nucleus shape was shown to depend on developmental context but not seeding density. Both smaller cell volumes and flatter nuclei were found to correlate with increased expression of markers for mesenchymal condensation as well as chondrogenic and osteogenic differentiation but a decreased expression of pre-condensation and adipogenic markers. Considering the data presented here, both seeding density and protocol significantly alter the morphology of mesenchymal stem cells even at very early stages of cell culture. Thus, these design parameters may play a critical role in the success of tissue engineering strategies seeking to recreate condensation events. However, a better understanding of how these changes in cell volume and nucleus shape relate to the differentiation of MSCs is important for prescribing precise seeding conditions necessary for the development of the desired tissue type. In a companion study (Part B, following), we address the effect of concomitant volume and shape changing stresses on spatiotemporal distribution of the cytoskeletal proteins actin and tubulin. Taken together, these studies bring us one step closer to our ultimate goal of elucidating the dynamics of nucleus and cell shape change as tissue templates grow (cell proliferation) and specialize (cell differentiation).

Acute Ketamine Administration Corrects Abnormal Inflammatory Bone Markers in Major Depressive Disorder

PubMed Central

Kadriu, Bashkim; Gold, Philip W; Luckenbaugh, David A; Lener, Marc S; Ballard, Elizabeth D; Niciu, Mark J; Henter, Ioline D; Park, Lawrence T; De Sousa, Rafael Teixeira; Yuan, Peixiong; Machado-Vieira, Rodrigo; Zarate, Carlos A

2017-01-01

Patients with major depressive disorder (MDD) have clinically relevant, significant decreases in bone mineral density (BMD). We sought to determine if predictive markers of bone inflammation—the osteoprotegerin (OPG)-RANK-RANKL system or osteopontin (OPN)—play a role in the bone abnormalities associated with MDD and, if so, whether ketamine treatment corrected the abnormalities. The OPG-RANK-RANKL system plays the principal role in determining the balance between bone resorption and bone formation. RANKL is the osteoclast differentiating factor and diminishes BMD. OPG is a decoy receptor for RANKL, thereby increasing BMD. OPN is the bone glue that acts as a scaffold between bone tissues matrix composition to bind them together and is an important component of bone strength and fracture resistance. Twenty-eight medication-free inpatients with treatment-resistant MDD and 16 healthy controls (HCs) participated in the study. Peripheral bone marker levels and their responses to IV ketamine infusion in MDD patients and HCs were measured at four time points: at baseline, and post-infusion at 230 minutes, Day 1, and Day 3. Patients with MDD had significant decreases in baseline OPG/RANKL ratio and in plasma OPN levels. Ketamine significantly increased both the OPG/RANKL ratio and plasma OPN levels and significantly decreased RANKL levels. Bone marker levels in HCs remained unaltered. We conclude that the OPG-RANK-RANKL system and the OPN system play important roles in the serious bone abnormalities associated with MDD. These data suggest that in addition to its antidepressant effects, ketamine also has a salutary effect on a major medical complication of depressive illness. PMID:28555075

Finasteride therapy does not alter bone turnover in men with benign prostatic hyperplasia--a Clinical Research Center study.

PubMed

Tollin, S R; Rosen, H N; Zurowski, K; Saltzman, B; Zeind, A J; Berg, S; Greenspan, S L

1996-03-01

Benign prostatic hyperplasia is often treated with finasteride, which inhibits the conversion of testosterone to dihydrotestosterone (DHT). Aside from the prostate, other androgen-dependent tissues seem to be unaffected by selective DHT deficiency, but the effect on bone density in humans has not yet been defined. To study this question, we compared indices of bone turnover and bone mineral density in 35 men treated with finasteride with controls. Bone resorption was assessed by measuring urinary excretion of N-telopeptide cross-links of type I collagen and hydroxyproline, and bone formation was assessed by measuring serum osteoncalcin and bone-specific alkaline phosphatase. Bone density of the spine and hip were assessed by dual energy x-ray absorptiometry. We found that finasteride-treated patients had mean DHT levels 81% lower than controls (P < 0.0001). There were no significant differences between the two groups in any of the markers of bone turnover or measures of bone density. These results suggest that testosterone can maintain bone density in men even in the absence of DHT. Although long term studies are needed, our results suggest that men who take finasteride are not at increased risk for bone loss.

Immune deficiency could be an early risk factor for altered insulin sensitivity in antiretroviral-naive HIV-1-infected patients: the ANRS COPANA cohort.

PubMed

Boufassa, Faroudy; Goujard, Cécile; Viard, Jean-Paul; Carlier, Robert; Lefebvre, Bénédicte; Yeni, Patrick; Bouchaud, Olivier; Capeau, Jacqueline; Meyer, Laurence; Vigouroux, Corinne

2012-01-01

The relationships between immunovirological status, inflammatory markers, insulin resistance and fat distribution have not been studied in recently diagnosed (<1 year) antiretroviral-naive HIV-1-infected patients. We studied 214 antiretroviral-naive patients at enrolment in the metabolic substudy of the ANRS COPANA cohort. We measured clinical, immunovirological and inflammatory parameters, glucose/insulin during oral glucose tolerance test (OGTT), adipokines, subcutaneous and visceral fat surfaces (subcutaneous adipose tissue [SAT] and visceral adipose tissue [VAT], assessed by computed tomography) and the body fat distribution based on dual-energy X-ray absorptiometry (DEXA). Median age was 36 years; 28% of the patients were female and 35% of sub-Saharan origin; 20% had low CD4(+) T-cell counts (≤200/mm(3)). Patients with low CD4(+) T-cell counts were older and more frequently of sub-Saharan Africa origin, had lower body mass index (BMI) but no different SAT/VAT ratio and fat distribution than other patients. They also had lower total, low-density lipoprotein and high-density lipoprotein cholesterolaemia, higher triglyceridaemia and post-OGTT glycaemia, higher markers of insulin resistance (insulin during OGTT and homeostasis model assessment of insulin resistance) and of inflammation (high-sensitivity C-reactive protein, IL-6, tumour necrosis factor (TNF)-α, sTNFR1 and sTNFR2). After adjustment for age, sex, geographic origin, BMI and waist circumference, increased insulin resistance was not related to any inflammatory marker. In multivariate analysis, low CD4(+) T-cell count was an independent risk factor for altered insulin sensitivity (β-coefficient for HOMA-IR: +0.90; P=0.001; CD4(+) T-cell count >500/mm(3) as the reference), in addition to older age (β: +0.26 for a 10-year increase; P=0.01) and higher BMI (β: +0.07 for a 1-kg/m(2) increase; P=0.003). In ART-naive patients, severe immune deficiency but not inflammation could be an early risk factor for altered insulin sensitivity.

Home-based resistance training improves femoral bone mineral density in women on hormone therapy.

PubMed

Judge, James Oat; Kleppinger, Alison; Kenny, Anne; Smith, Jo-Anne; Biskup, Brad; Marcella, Glenn

2005-09-01

This study tested whether moderate resistance training would improve femoral bone mineral density (BMD) in long-term users of hormone therapy with low BMD. The study was a 2-year randomized, controlled, trial (RCT) of moderate resistance training of either the lower extremity or the upper extremity. Eighty-five women participated in a 6-month observation period. The setting was center-based and home-based training. The participants were 189 women aged 59-78 years, with total femur T-scores from -0.8 to -2.8 and on hormone therapy (HT) for a minimum of 2 years (mean 11.8 years); 153 completed the trial. Lower extremity training used weight belts (mean 7.8 kg) in step-ups and chair rises; upper extremity training used elastic bands and dumbbells. Measurements were BMD and body composition [dual-energy X-ray absorptiometry (DXA)], bone turnover markers. Total femoral BMD showed a downward trend during the observation period: 0.35%+/-0.18% (P=0.14). The response to training was similar in the upper and lower groups in the primary outcomes. At 2 years, total femoral BMD increased 1.5% (95% CI 0.8%-2.2%) in the lower group and 1.8% (95% CI 1.1%-2.5%) in the upper group. Trochanter BMD increased 2.4% (95% CI 1.3%-3.5%) in the lower group and 2.5% (95% CI 1.4%-3.6%) in the upper group (for both analyses time effect P<0.001). At 1 year, a bone resorption marker (C-telopeptide) decreased 9% (P=0.04). Bone formation markers, bone-specific alkaline phosphatase, decreased 5% (P<0.001), and N-terminal type I procollagen peptide decreased 7% (P=0.01). Body composition (percent lean and percent body fat) was maintained in both groups. We concluded that long-term moderate resistance training reversed bone loss, decreased bone turnover, increased femur BMD, and maintained body composition. The similarity of response in upper and lower groups supports a systemic response rather than a site-specific response to moderate resistance training.

Short communication: Effect of commercial or depurinized milk diet on plasma advanced oxidation protein products, cardiovascular markers, and bone marrow CD34+ stem cell potential in rat experimental hyperuricemia.

PubMed

Kocic, Gordana; Sokolovic, Dusan; Jevtovic, Tatjana; Cvetkovic, Tatjana; Veljkovic, Andrej; Kocic, Hristina; Stojanovic, Svetlana; Jovanovic, Aneta; Jovanovic, Jelena; Zivkovic, Petar

2014-11-01

Cardiovascular repair and myocardial contractility may be improved by migration of bone marrow stem cells (BMSC) and their delivery to the site of injury, a process known as BMSC homing. The aim of our study was to examine the dietary effect of a newly patented depurinized milk (DP) that is almost free of uric acid and purine and pyrimidine compounds compared with a standard commercial 1.5% fat UHT milk diet or allopurinol therapy in rat experimental hyperuricemia. Bone marrow stem cell potential (BMCD34(+), CD34-postive bone marrow cells), plasma oxidative stress parameters [advanced oxidation protein products, AOPP) and thiobarbituric acid reactive substances (TBARS)], myocardial damage markers [creatine phosphokinase (CPK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH)], plasma cholesterol, and high-density lipoprotein cholesterol were investigated. The DP milk diet significantly increased the number of BMCD34(+) stem cells compared with commercial UHT milk. Allopurinol given alone also increased the number of BMCD34(+). Hyperuricemia caused a significant increase in all plasma enzyme markers for myocardial damage (CPK, LDH, and AST). A cardioprotective effect was achieved with allopurinol but almost equally with DP milk and more than with commercial milk. Regarding plasma AOPP, TBARS, and cholesterol levels, the most effective treatment was DP milk. In conclusion, the protective role of a milk diet on cardiovascular function may be enhanced through the new depurinized milk diet, which may improve cardiovascular system function via increased bone marrow stem cell regenerative potential, decreased plasma oxidative stress parameters, and decreased levels of myocardial damage markers and cholesterol. New dairy technology strategies focused on eliminating harmful milk compounds should be completely nontoxic. Novel milk products should be tested for their ability to improve tissue repair and function. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Relationship between plasma bilirubin level and oxidative stress markers in HIV-infected patients on atazanavir- vs. efavirenz-based antiretroviral therapy.

PubMed

Estrada, V; Monge, S; Gómez-Garre, M D; Sobrino, P; Masiá, M; Berenguer, J; Portilla, J; Viladés, C; Martínez, E; Blanco, J R

2016-10-01

Chronic oxidative stress (OS) may play a role in cardiovascular disease in HIV-infected patients, and increased bilirubin levels may have a beneficial role in counteracting OS. Atazanavir (ATV) inhibits UDP-glucuronosyl-transferase 1A1 (UGT1A1), thus increasing unconjugated bilirubin levels. We aimed to compare changes in OS markers in patients on ATV/ritonavir (ATV/r)- vs. efavirenz (EFV)-based first-line antiretroviral therapy (ART). A multicentre, prospective cohort study of HIV-infected patients who started first-line ART with either ATV/r or EFV was conducted. Lipoprotein-associated phospholipase A2 (Lp-PLA2), myeloperoxidase (MPO) and oxidized low-density lipoprotein (oxLDL) were measured for 145 patients in samples obtained at baseline and after at least 9 months of ART during which the initial regimen was maintained and the patient was virologically suppressed. The change in OS markers was modelled using multiple linear regressions adjusting for baseline values and confounders. After adjustment for baseline variables, patients on ATV/r had a significantly greater decrease in Lp-PLA2 [estimated difference -16.3; 95% confidence interval (CI) -31.4, -1.25; P = 0.03] and a significantly smaller increase in OxLDL (estimated difference -21.8; 95% CI -38.0, -5.6; P < 0.01) relative to those on EFV, whereas changes in MPO were not significantly different (estimated difference 1.2; 95% CI -14.3, 16.7; P = 0.88). Adjusted changes in bilirubin were significantly greater for the ATV/r group than for the EFV group (estimated difference 1.33 mg/dL; 95% CI 1.03, 1.52 mg/dL; P < 0.01). Changes in bilirubin and changes in OS markers were significantly correlated. When compared with EFV, ATV/r-based therapy was associated with lower levels of oxidative stress biomarkers, which was in part attributable to increased bilirubin levels. © 2016 British HIV Association.

Effect of 6-month calorie restriction and exercise on serum and liver lipids and markers of liver function.

PubMed

Larson-Meyer, D Enette; Newcomer, Bradley R; Heilbronn, Leonie K; Volaufova, Julia; Smith, Steven R; Alfonso, Anthony J; Lefevre, Michael; Rood, Jennifer C; Williamson, Donald A; Ravussin, Eric

2008-06-01

Nonalcoholic fatty liver disease (NAFLD) and its association with insulin resistance are increasingly recognized as major health burdens. The main objectives of this study were to assess the relation between liver lipid content and serum lipids, markers of liver function and inflammation in healthy overweight subjects, and to determine whether caloric restriction (CR) (which improves insulin resistance) reduces liver lipids in association with these same measures. Forty-six white and black overweight men and women (BMI = 24.7-31.3 kg/m(2)) were randomized to "control (CO)" = 100% energy requirements; "CR" = 25%; "caloric restriction and increased structured exercise (CR+EX)"= 12.5% CR + 12.5% increase in energy expenditure through exercise; or "low-calorie diet (LCD)" = 15% weight loss by liquid diet followed by weight-maintenance, for 6 months. Liver lipid content was assessed by magnetic resonance spectroscopy (MRS) and computed tomography (CT). Lipid concentrations, markers of liver function (alanine aminotransferase (ALT), alkaline phosphatase (ALK)), and whole-body inflammation (tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP)) were measured in fasting blood. At baseline, increased liver lipid content (by MRS) correlated (P < 0.05) with elevated fasting triglyceride (r = 0.52), ALT (r = 0.42), and hsCRP (r = 0.33) concentrations after adjusting for sex, race, and alcohol consumption. With CR, liver lipid content was significantly lowered by CR, CR+EX, and LCD (detected by MRS only). The reduction in liver lipid content, however, was not significantly correlated with the reduction in triglycerides (r = 0.26; P = 0.11) or with the changes in ALT, high-density lipoprotein (HDL)-cholesterol, or markers of whole-body inflammation. CR may be beneficial for reducing liver lipid and lowering triglycerides in overweight subjects without known NAFLD.

Effect of 6-Month Calorie Restriction and Exercise on Serum and Liver Lipids and Markers of Liver Function

PubMed Central

Larson-Meyer, D. Enette; Newcomer, Bradley R.; Heilbronn, Leonie K.; Volaufova, Julia; Smith, Steven R.; Alfonso, Anthony J.; Lefevre, Michael; Rood, Jennifer C.; Williamson, Donald A.; Ravussin, Eric

2009-01-01

objective Nonalcoholic fatty liver disease (NAFLD) and its association with insulin resistance are increasingly recognized as major health burdens. The main objectives of this study were to assess the relation between liver lipid content and serum lipids, markers of liver function and inflammation in healthy overweight subjects, and to determine whether caloric restriction (CR) (which improves insulin resistance) reduces liver lipids in association with these same measures. Methods and Procedures Forty-six white and black overweight men and women (BMI = 24.7-31.3 kg/m2) were randomized to “control (CO)” = 100% energy requirements; “CR” = 25%; “caloric restriction and increased structured exercise (CR+EX)”= 12.5% CR + 12.5% increase in energy expenditure through exercise; or “low-calorie diet (LCD)” = 15% weight loss by liquid diet followed by weight-maintenance, for 6 months. Liver lipid content was assessed by magnetic resonance spectroscopy (MRS) and computed tomography (CT). Lipid concentrations, markers of liver function (alanine aminotransferase (ALT), alkaline phosphatase (ALK)), and whole-body inflammation (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP)) were measured in fasting blood. Results At baseline, increased liver lipid content (by MRS) correlated (P < 0.05) with elevated fasting triglyceride (r = 0.52), ALT (r = 0.42), and hsCRP (r = 0.33) concentrations after adjusting for sex, race, and alcohol consumption. With CR, liver lipid content was significantly lowered by CR, CR+EX, and LCD (detected by MRS only). The reduction in liver lipid content, however, was not significantly correlated with the reduction in triglycerides (r = 0.26; P = 0.11) or with the changes in ALT, high-density lipoprotein (HDL)-cholesterol, or markers of whole-body inflammation. Discussion CR may be beneficial for reducing liver lipid and lowering triglycerides in overweight subjects without known NAFLD. PMID:18421281

Laboratory markers of cardiovascular risk in pediatric SLE: the APPLE baseline cohort.

PubMed

Ardoin, S P; Schanberg, L E; Sandborg, C; Yow, E; Barnhart, H X; Mieszkalski, K l; Ilowite, N T; von Scheven, E; Eberhard, A; Levy, D M; Kimura, Y; Silverman, E; Bowyer, S L; Punaro, L; Singer, N G; Sherry, D D; McCurdy, D; Klein-Gitelman, M; Wallace, C; Silver, R; Wagner-Weiner, L; Higgins, G C; Brunner, H I; Jung, L K; Imundo, L; Soep, J B; Reed, A M

2010-10-01

As part of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) Trial, a prospective multicenter cohort of 221 children and adolescents with systemic lupus erythematosus (SLE) (mean age 15.7 years, 83% female) underwent baseline measurement of markers of cardiovascular risk, including fasting levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), lipoprotein A (Lpa), homocysteine and high-sensitivity C-reactive protein (hs-CRP). A cross-sectional analysis of the baseline laboratory values and clinical characteristics of this cohort was performed. Univariable relationships between the cardiovascular markers of interest and clinical variables were assessed, followed by multivariable linear regression modeling. Mean levels of LDL, HDL, Lpa, TG, hs-CRP and homocysteine were in the normal or borderline ranges. In multivariable analysis, increased Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), prednisone dose, and hypertension (HTN) were independently associated with higher LDL levels. Higher hs-CRP and creatinine clearance were independently related to lower HDL levels. Higher body mass index (BMI), prednisone dose, and homocysteine levels were independently associated with higher TG levels. Only Hispanic or non-White status predicted higher Lpa levels. Proteinuria, higher TG and lower creatinine clearance were independently associated with higher homocysteine levels, while use of multivitamin with folate predicted lower homocysteine levels. Higher BMI, lower HDL, and longer SLE disease duration, but not SLEDAI, were independently associated with higher hs-CRP levels. The R(2) for these models ranged from 7% to 23%. SLE disease activity as measured by the SLEDAI was associated only with higher LDL levels and not with hs-CRP. Markers of renal injury (HTN, proteinuria, and creatinine clearance) were independently associated with levels of LDL, HDL, and homocysteine, highlighting the importance of renal status in the cardiovascular health of children and adolescents with SLE. Future longitudinal analysis of the APPLE cohort is needed to further examine these relationships.

Contribution of Serum Inflammatory Markers to Changes in Bone Mineral Content and Density in Postmenopausal Women: A 1-Year Investigation

PubMed Central

Gertz, ER; Silverman, NE; Wise, KS; Hanson, KB; Alekel, DL; Stewart, JW; Perry, CD; Bhupathiraju, SN; Kohut, ML; Van Loan, MD

2010-01-01

Bone formation and resorption are influenced by inflammatory processes. We examined the relationships among inflammatory markers and bone mineral content and density (BMC, BMD) and determined the contribution of inflammatory markers to 1-year changes in BMC and BMD in healthy postmenopausal women. This analysis included 242 women at baseline from our parent Soy Isoflavones for Reducing Bone Loss (SIRBL) project who were randomly assigned to one of three treatment groups: placebo, 80 mg/d soy isoflavones, or 120 mg/d soy isoflavones. BMD and BMC from the lumbar spine (LS), total proximal femur (hip), and whole body were measured by dual energy x-ray absorptiometry (DXA) and the 4% distal tibia (DT) by peripheral quantitative computed tomography (pQCT). Serum inflammatory markers (C-reactive protein (CRP), interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α), and white blood cell count (WBC)) were measured at baseline, 6 and 12 months. Due to attrition or missing values, data analysis at 12 months includes only 235 women. Significant associations among Il-6, TNF-α, and WBC were observed with percent change in LS, hip, and whole body BMC and BMD. Multiple regression analysis indicated that in combination inflammatory markers accounted for 1.1% to 6.1% of the variance to the observed 12 month changes in BMC and BMD. Our results suggest that modifying inflammatory markers, even in healthy postmenopausal women, may possibly reduce bone loss. PMID:20605499

The use of genomic information increases the accuracy of breeding value predictions for sea louse (Caligus rogercresseyi) resistance in Atlantic salmon (Salmo salar).

PubMed

Correa, Katharina; Bangera, Rama; Figueroa, René; Lhorente, Jean P; Yáñez, José M

2017-01-31

Sea lice infestations caused by Caligus rogercresseyi are a main concern to the salmon farming industry due to associated economic losses. Resistance to this parasite was shown to have low to moderate genetic variation and its genetic architecture was suggested to be polygenic. The aim of this study was to compare accuracies of breeding value predictions obtained with pedigree-based best linear unbiased prediction (P-BLUP) methodology against different genomic prediction approaches: genomic BLUP (G-BLUP), Bayesian Lasso, and Bayes C. To achieve this, 2404 individuals from 118 families were measured for C. rogercresseyi count after a challenge and genotyped using 37 K single nucleotide polymorphisms. Accuracies were assessed using fivefold cross-validation and SNP densities of 0.5, 1, 5, 10, 25 and 37 K. Accuracy of genomic predictions increased with increasing SNP density and was higher than pedigree-based BLUP predictions by up to 22%. Both Bayesian and G-BLUP methods can predict breeding values with higher accuracies than pedigree-based BLUP, however, G-BLUP may be the preferred method because of reduced computation time and ease of implementation. A relatively low marker density (i.e. 10 K) is sufficient for maximal increase in accuracy when using G-BLUP or Bayesian methods for genomic prediction of C. rogercresseyi resistance in Atlantic salmon.

Paraoxonase responses to exercise and niacin therapy in men with metabolic syndrome.

PubMed

Taylor, James Kyle; Plaisance, Eric P; Mahurin, A Jack; Mestek, Michael L; Moncada-Jimenez, Jose; Grandjean, Peter W

2015-01-01

Our purpose was to characterize changes in paraoxonase 1 (PON1) activity and concentration after single aerobic exercise sessions conducted before and after 6 weeks of niacin therapy in men with metabolic syndrome (MetS). Twelve men with MetS expended 500 kcal by walking at 65% of VO2max before and after a 6-week regimen of niacin. Niacin doses were titrated by 500 mg/week from 500 to 1500 mg/day and maintained at 1500 mg/day for the last 4 weeks. Fasting blood samples were collected before and 24 hours after each exercise session and analyzed for PON1 activity, PON1 concentration, myeloperoxidase (MPO), apolipoprotein A1, oxidized low-density lipoprotein (oLDL), lipoprotein particle sizes and concentrations. PON1 activity, PON1 concentration, MPO, and oLDL were unaltered following the independent effects of exercise and niacin (P > 0.05 for all). High-density lipoprotein particle size decreased by 3% (P = 0.040) and concentrations of small very low-density lipoprotein increased (P = 0.016) following exercise. PON1 activity increased 6.1% (P = 0.037) and PON1 concentrations increased 11.3% (P = 0.015) with the combination of exercise and niacin. Exercise and niacin works synergistically to increase PON1 activity and concentration with little or no changes in lipoproteins or markers of lipid oxidation.

Effect of two forms of alendronate administration upon bone mass after two years of treatment.

PubMed

Sosa, M; Hernández, D; Segarra, M C; Gómez, A; de la Peña, E; Betancor, P

2002-01-01

The efficacy of alendronate in slowing the loss of bone mass, or even in increasing it, in osteoporotic patients and thus reducing the risk of new fractures has been described. Nevertheless, the way of taking this drug, together with its side effects, sometimes produces withdrawals. In this study, we analyzed if an alternative way of taking the alendronate improves the follow-up of the treatment and if it had the same effect on bone mineral metabolism than the traditional way of prescription. An open, intention-to-treat study, with follow-up of 2 yr was conducted. Eighty women suffering from postmenopausal osteoporosis were included in the study. They were classified in a random manner into two groups, each one of them received 10 mg/d alendronate, together with 1.2 g of calcium and 800 IU of Vitamin D3. Group I received the drug fasting, before breakfast, as usually prescribed and group II received the alendronate fasting, at noon, before lunch. Biochemical markers of bone remodeling were determined. Total alkaline phosphatase, osteocalcin, tartrate-resistant acid phosphatase, urine calcium/creatinine ratio, crosslinked N-telopeptides of type I collagen/creatinine ratio, serum calcium, and parathyroid hormone were also determined, and a lateral dorsolumbar radiography of the spine was performed. Bone mineral density was determined in the lumbar spine by dual-energy X-ray absorptiometry and quantitative computed tomography and by dual-energy X-ray absorptiometry in the proximal femur. Both groups showed an increase in bone mineral density in the lumbar spine and in the proximal femur, which was statistically significant after 1 yr of treatment in the range between 1.5% and 4.3%, depending on the anatomical localization where bone mineral density was measured. There was also an important decrease in the biochemical markers of bone remodeling, between 5.6% and 42.5%, depending on the biochemical marker; the decrease of amino-terminal telopetide during the first year was more important. The group that received alendronate in the morning reported a significantly higher number of withdrawals than the group that received the drug at noon. The alternative administration of 10 mg alendronate at noon had the same effect on bone mineral metabolism than its traditional administration in the morning, but the rate of withdrawals was significantly lower.

Protective Effects of Vildagliptin against Pioglitazone-Induced Bone Loss in Type 2 Diabetic Rats

PubMed Central

Kwak, Kyung Min; Kim, Ju-Young; Yu, Seung Hee; Lee, Sihoon; Kim, Yeun Sun; Park, Ie Byung; Kim, Kwang-Won; Lee, Kiyoung

2016-01-01

Long-term use of thiazolidinediones (TZDs) is associated with bone loss and an increased risk of fracture in patients with type 2 diabetes (T2DM). Incretin-based drugs (glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors) have several benefits in many systems in addition to glycemic control. In a previous study, we reported that exendin-4 might increase bone mineral density (BMD) by decreasing the expression of SOST/sclerostin in osteocytes in a T2DM animal model. In this study, we investigated the effects of a DPP-4 inhibitor on TZD-induced bone loss in a T2DM animal model. We randomly divided 12-week-old male Zucker Diabetic Fatty (ZDF) rats into four groups; control, vildagliptin, pioglitazone, and vildagliptin and pioglitazone combination. Animals in each group received the respective treatments for 5 weeks. We performed an intraperitoneal glucose tolerance test (IPGTT) before and after treatment. BMD and the trabecular micro-architecture were measured by DEXA and micro CT, respectively, at the end of the treatment. The circulating levels of active GLP-1, bone turnover markers, and sclerostin were assayed. Vildagliptin treatment significantly increased BMD and trabecular bone volume. The combination therapy restored BMD, trabecular bone volume, and trabecular bone thickness that were decreased by pioglitazone. The levels of the bone formation marker, osteocalcin, decreased and that of the bone resorption marker, tartrate-resistant acid phosphatase (TRAP) 5b increased in the pioglitazone group. These biomarkers were ameliorated and the pioglitazone-induced increase in sclerostin level was lowered to control values by the addition of vildagliptin. In conclusion, our results indicate that orally administered vildagliptin demonstrated a protective effect on pioglitazone-induced bone loss in a type 2 diabetic rat model. PMID:27997588

Protective Effects of Vildagliptin against Pioglitazone-Induced Bone Loss in Type 2 Diabetic Rats.

PubMed

Eom, Young Sil; Gwon, A-Ryeong; Kwak, Kyung Min; Kim, Ju-Young; Yu, Seung Hee; Lee, Sihoon; Kim, Yeun Sun; Park, Ie Byung; Kim, Kwang-Won; Lee, Kiyoung; Kim, Byung-Joon

2016-01-01

Long-term use of thiazolidinediones (TZDs) is associated with bone loss and an increased risk of fracture in patients with type 2 diabetes (T2DM). Incretin-based drugs (glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors) have several benefits in many systems in addition to glycemic control. In a previous study, we reported that exendin-4 might increase bone mineral density (BMD) by decreasing the expression of SOST/sclerostin in osteocytes in a T2DM animal model. In this study, we investigated the effects of a DPP-4 inhibitor on TZD-induced bone loss in a T2DM animal model. We randomly divided 12-week-old male Zucker Diabetic Fatty (ZDF) rats into four groups; control, vildagliptin, pioglitazone, and vildagliptin and pioglitazone combination. Animals in each group received the respective treatments for 5 weeks. We performed an intraperitoneal glucose tolerance test (IPGTT) before and after treatment. BMD and the trabecular micro-architecture were measured by DEXA and micro CT, respectively, at the end of the treatment. The circulating levels of active GLP-1, bone turnover markers, and sclerostin were assayed. Vildagliptin treatment significantly increased BMD and trabecular bone volume. The combination therapy restored BMD, trabecular bone volume, and trabecular bone thickness that were decreased by pioglitazone. The levels of the bone formation marker, osteocalcin, decreased and that of the bone resorption marker, tartrate-resistant acid phosphatase (TRAP) 5b increased in the pioglitazone group. These biomarkers were ameliorated and the pioglitazone-induced increase in sclerostin level was lowered to control values by the addition of vildagliptin. In conclusion, our results indicate that orally administered vildagliptin demonstrated a protective effect on pioglitazone-induced bone loss in a type 2 diabetic rat model.

Glyoxysomes in Megagamethophyte of Germinating Ponderosa Pine Seeds 12

PubMed Central

Ching, Te May

1970-01-01

Decoated ponderosa pine (Pinus ponderosa Laws) seeds contained 40% lipids, which were mainly stored in megagametophytic tissue and were utilized or converted to sugars via the glyoxylate cycle during germination. Mitochondria and glyoxysomes were isolated from the tissue by sucrose density gradient centrifugation at different stages of germination. It was found that isocitrate lyase, malate synthase, and catalase were mainly bound in glyoxysomes. Aconitase and fumarase were chiefly localized in mitochondria, whereas citrate synthase was common for both. Both organelles increased in quantity and specific activity of their respective marker enzymes with the advancement of germination. When the megagametophyte was exhausted at the end of germination, the quantity of these organelles and the activity of their marker enzymes decreased abruptly. At the stage of highest lipolysis, the isolated mitochondria and glyoxysomes were able to synthesize protein from labeled amino acids. Both organellar fractions contained RNA and DNA. Some degree of autonomy in glyoxysomes is indicated. Images PMID:16657489

Low-dose estrogen therapy for prevention of osteoporosis: working our way back to monotherapy.

PubMed

Richman, Susan; Edusa, Valentine; Fadiel, Ahmed; Naftolin, Frederick

2006-01-01

The risks of low bone mineral density, osteoporosis and fractures, are major concerns in postmenopausal women. Although postmenopausal hormone therapy is effective for reducing these risks, safety issues have been raised by the results of studies such as the Women's Health Initiative. Although there are scientifically valid reasons to be wary of the general applicability of the Women's Health Initiative findings, the study has underscored the continuing need for research into new forms of menopausal hormone therapy. Low-dose transdermal estrogen monotherapy can preserve bone density while relieving vasomotor symptoms. Transdermal administration may offer advantages, including lack of first-pass liver metabolism, which permits the use of lower doses and avoids a negative impact on the lipid profile. Moreover, a recently published 2-year study of ultra-low-dose transdermal estrogen monotherapy in an older population similar to that of the WHI reported significant increases in bone mineral density, accompanied by significant reductions in markers of bone turnover, with no increased risk of endometrial hyperplasia or other side effects. Additional studies are warranted to shed further light on the possible benefits of low-dose estrogen monotherapy for the prevention of bone loss in postmenopausal women.

Increased density of DISC1-immunoreactive oligodendroglial cells in fronto-parietal white matter of patients with paranoid schizophrenia.

PubMed

Bernstein, Hans-Gert; Jauch, Esther; Dobrowolny, Henrik; Mawrin, Christian; Steiner, Johann; Bogerts, Bernhard

2016-09-01

Profound white matter abnormalities have repeatedly been described in schizophrenia, which involve the altered expression of numerous oligodendrocyte-associated genes. Transcripts of the disrupted-in-schizophrenia 1 (DISC1) gene, a key susceptibility factor in schizophrenia, have recently been shown to be expressed by oligodendroglial cells and to negatively regulate oligodendrocyte differentiation and maturation. To learn more about the putative role(s) of oligodendroglia-associated DISC1 in schizophrenia, we analyzed the density of DISC1-immunoreactive oligodendrocytes in the fronto-parietal white matter in postmortem brains of patients with schizophrenia. Compared with controls (N = 12) and cases with undifferentiated/residual schizophrenia (N = 6), there was a significantly increased density of DISC1-expressing glial cells in paranoid schizophrenia (N = 12), which unlikely resulted from neuroleptic treatment. Pathophysiologically, over-expression of DISC1 protein(s) in white matter oligodendrocytes might add to the reduced levels of two myelin markers, 2',3'-cyclic-nucleotide 3'-phosphodiesterase and myelin basic protein in schizophrenia. Moreover, it might significantly contribute to cell cycle abnormalities as well as to deficits in oligodendroglial cell differentiation and maturation found in schizophrenia.

Genome Wide Characterization of Short Tandem Repeat Markers in Sweet Orange (Citrus sinensis)

PubMed Central

Biswas, Manosh Kumar; Xu, Qiang; Mayer, Christoph; Deng, Xiuxin

2014-01-01

Sweet orange (Citrus sinensis) is one of the major cultivated and most-consumed citrus species. With the goal of enhancing the genomic resources in citrus, we surveyed, developed and characterized microsatellite markers in the ≈347 Mb sequence assembly of the sweet orange genome. A total of 50,846 SSRs were identified with a frequency of 146.4 SSRs/Mbp. Dinucleotide repeats are the most frequent repeat class and the highest density of SSRs was found in chromosome 4. SSRs are non-randomly distributed in the genome and most of the SSRs (62.02%) are located in the intergenic regions. We found that AT-rich SSRs are more frequent than GC-rich SSRs. A total number of 21,248 SSR primers were successfully developed, which represents 89 SSR markers per Mb of the genome. A subset of 950 developed SSR primer pairs were synthesized and tested by wet lab experiments on a set of 16 citrus accessions. In total we identified 534 (56.21%) polymorphic SSR markers that will be useful in citrus improvement. The number of amplified alleles ranges from 2 to 12 with an average of 4 alleles per marker and an average PIC value of 0.75. The newly developed sweet orange primer sequences, their in silico PCR products, exact position in the genome assembly and putative function are made publicly available. We present the largest number of SSR markers ever developed for a citrus species. Almost two thirds of the markers are transferable to 16 citrus relatives and may be used for constructing a high density linkage map. In addition, they are valuable for marker-assisted selection studies, population structure analyses and comparative genomic studies of C. sinensis with other citrus related species. Altogether, these markers provide a significant contribution to the citrus research community. PMID:25148383

Genome wide characterization of short tandem repeat markers in sweet orange (Citrus sinensis).

PubMed

Biswas, Manosh Kumar; Xu, Qiang; Mayer, Christoph; Deng, Xiuxin

2014-01-01

Sweet orange (Citrus sinensis) is one of the major cultivated and most-consumed citrus species. With the goal of enhancing the genomic resources in citrus, we surveyed, developed and characterized microsatellite markers in the ≈347 Mb sequence assembly of the sweet orange genome. A total of 50,846 SSRs were identified with a frequency of 146.4 SSRs/Mbp. Dinucleotide repeats are the most frequent repeat class and the highest density of SSRs was found in chromosome 4. SSRs are non-randomly distributed in the genome and most of the SSRs (62.02%) are located in the intergenic regions. We found that AT-rich SSRs are more frequent than GC-rich SSRs. A total number of 21,248 SSR primers were successfully developed, which represents 89 SSR markers per Mb of the genome. A subset of 950 developed SSR primer pairs were synthesized and tested by wet lab experiments on a set of 16 citrus accessions. In total we identified 534 (56.21%) polymorphic SSR markers that will be useful in citrus improvement. The number of amplified alleles ranges from 2 to 12 with an average of 4 alleles per marker and an average PIC value of 0.75. The newly developed sweet orange primer sequences, their in silico PCR products, exact position in the genome assembly and putative function are made publicly available. We present the largest number of SSR markers ever developed for a citrus species. Almost two thirds of the markers are transferable to 16 citrus relatives and may be used for constructing a high density linkage map. In addition, they are valuable for marker-assisted selection studies, population structure analyses and comparative genomic studies of C. sinensis with other citrus related species. Altogether, these markers provide a significant contribution to the citrus research community.

Genomic Characterization of DArT Markers Based on High-Density Linkage Analysis and Physical Mapping to the Eucalyptus Genome

PubMed Central

Petroli, César D.; Sansaloni, Carolina P.; Carling, Jason; Steane, Dorothy A.; Vaillancourt, René E.; Myburg, Alexander A.; da Silva, Orzenil Bonfim; Pappas, Georgios Joannis; Kilian, Andrzej; Grattapaglia, Dario

2012-01-01

Diversity Arrays Technology (DArT) provides a robust, high throughput, cost-effective method to query thousands of sequence polymorphisms in a single assay. Despite the extensive use of this genotyping platform for numerous plant species, little is known regarding the sequence attributes and genome-wide distribution of DArT markers. We investigated the genomic properties of the 7,680 DArT marker probes of a Eucalyptus array, by sequencing them, constructing a high density linkage map and carrying out detailed physical mapping analyses to the Eucalyptus grandis reference genome. A consensus linkage map with 2,274 DArT markers anchored to 210 microsatellites and a framework map, with improved support for ordering, displayed extensive collinearity with the genome sequence. Only 1.4 Mbp of the 75 Mbp of still unplaced scaffold sequence was captured by 45 linkage mapped but physically unaligned markers to the 11 main Eucalyptus pseudochromosomes, providing compelling evidence for the quality and completeness of the current Eucalyptus genome assembly. A highly significant correspondence was found between the locations of DArT markers and predicted gene models, while most of the 89 DArT probes unaligned to the genome correspond to sequences likely absent in E. grandis, consistent with the pan-genomic feature of this multi-Eucalyptus species DArT array. These comprehensive linkage-to-physical mapping analyses provide novel data regarding the genomic attributes of DArT markers in plant genomes in general and for Eucalyptus in particular. DArT markers preferentially target the gene space and display a largely homogeneous distribution across the genome, thereby providing superb coverage for mapping and genome-wide applications in breeding and diversity studies. Data reported on these ubiquitous properties of DArT markers will be particularly valuable to researchers working on less-studied crop species who already count on DArT genotyping arrays but for which no reference genome is yet available to allow such detailed characterization. PMID:22984541

Low bone mineral density and fragility fractures in permanent vegetative state patients.

PubMed

Oppl, Bastian; Michitsch, Gabriele; Misof, Barbara; Kudlacek, Stefan; Donis, Johann; Klaushofer, Klaus; Zwerina, Jochen; Zwettler, Elisabeth

2014-01-01

Disuse of the musculoskeletal system causes bone loss. Whether patients in vegetative state, a dramatic example of immobilization after severe brain injury, suffer from bone loss and fractures is currently unknown. Serum markers of bone turnover, bone mineral density (BMD) measurements, and clinical data were cross-sectionally analyzed in 30 consecutive vegetative state patients of a dedicated apallic care unit between 2003 and 2007 and compared with age- and sex-matched healthy individuals. Vegetative state patients showed low calcium levels and vitamin D deficiency compared with healthy controls. Serum bone turnover markers revealed high turnover as evidenced by markedly elevated carboxy-terminal telopeptide of type I collagen (β-crosslaps) and increased levels of alkaline phosphatase. BMD measured by dual-energy X-ray absorptiometry (DXA) scanning showed strongly decreased T- and Z-scores for hip and spine. Over a period of 5 years, 8 fragility fractures occurred at peripheral sites in 6 of 30 patients (n = 3 femur, n = 2 tibia, n = 2 fibula, n = 1 humerus). In conclusion, high bone turnover and low BMD is highly prevalent in vegetative state patients, translating into a clinically relevant problem as shown by fragility fractures in 20% of patients over a time period of 5 years. . © 2014 American Society for Bone and Mineral Research.

A Case of Teriparatide on Pregnancy-Induced Osteoporosis

PubMed Central

Lee, Seok Hong; Hong, Moon-Ki; Park, Seung Won; Park, Hyoung-Moo; Kim, Jaetaek

2013-01-01

Pregnancy-induced osteoporosis is a rare disorder characterized by fragility fracture and low bone mineral density (BMD) during or shortly after pregnancy, and its etiology is still unclear. We experienced a case of a 39-year-old woman who suffered from lumbago 3 months after delivery. Biochemical evidence of increased bone resorption is observed without secondary causes of osteoporosis. Radiologic examination showed multiple compression fractures on her lumbar vertebrae. We report a case of patient with pregnancy-induced osteoporosis improved her clinical symptom, BMD and bone turnover marker after teriparatide therapy. PMID:24524067

Short-Term Effects of Kefir-Fermented Milk Consumption on Bone Mineral Density and Bone Metabolism in a Randomized Clinical Trial of Osteoporotic Patients

PubMed Central

Tung, Yu-Tang; Kao, Chao-Chih; Hu, Fu-Chang; Chen, Chuan-Mu

2015-01-01

Milk products are good sources of calcium that may reduce bone resorption and help prevent bone loss as well as promote bone remodeling and increase bone formation. Kefir is a product made by kefir grains that degrade milk proteins into various peptides with health-promoting effects, including antithrombotic, antimicrobial and calcium-absorption enhancing bioactivities. In a controlled, parallel, double-blind intervention study over 6 months, we investigated the effects of kefir-fermented milk (1,600 mg) supplemented with calcium bicarbonate (CaCO3, 1,500 mg) and bone metabolism in 40 osteoporosis patients, and compared them with CaCO3 alone without kefir supplements. Bone turnover markers were measured in fasting blood samples collected before therapy and at 1, 3, and 6 months. Bone mineral density (BMD) values at the spine, total hip, and hip femoral neck were assessed by dual-energy x-ray absorptiometry (DXA) at baseline and at 6 months. Among patients treated with kefir-fermented milk, the relationships between baseline turnover and 6 months changes in DXA-determined BMD were significantly improved. The serum β C-terminal telopeptide of type I collagen (β-CTX) in those with T-scores > -1 patients significantly decreased after three months treatment. The formation marker serum osteocalcin (OC) turned from negative to positive after 6 months, representing the effect of kefir treatment. Serum parathyroid hormone (PTH) increased significantly after treatment with kefir, but decreased significantly in the control group. PTH may promote bone remodeling after treatment with kefir for 6 months. In this pilot study, we concluded that kefir-fermented milk therapy was associated with short-term changes in turnover and greater 6-month increases in hip BMD among osteoporotic patients. Trial Registration: ClinicalTrials.gov NCT02361372 PMID:26655888

Short-Term Effects of Kefir-Fermented Milk Consumption on Bone Mineral Density and Bone Metabolism in a Randomized Clinical Trial of Osteoporotic Patients.

PubMed

Tu, Min-Yu; Chen, Hsiao-Ling; Tung, Yu-Tang; Kao, Chao-Chih; Hu, Fu-Chang; Chen, Chuan-Mu

2015-01-01

Milk products are good sources of calcium that may reduce bone resorption and help prevent bone loss as well as promote bone remodeling and increase bone formation. Kefir is a product made by kefir grains that degrade milk proteins into various peptides with health-promoting effects, including antithrombotic, antimicrobial and calcium-absorption enhancing bioactivities. In a controlled, parallel, double-blind intervention study over 6 months, we investigated the effects of kefir-fermented milk (1,600 mg) supplemented with calcium bicarbonate (CaCO3, 1,500 mg) and bone metabolism in 40 osteoporosis patients, and compared them with CaCO3 alone without kefir supplements. Bone turnover markers were measured in fasting blood samples collected before therapy and at 1, 3, and 6 months. Bone mineral density (BMD) values at the spine, total hip, and hip femoral neck were assessed by dual-energy x-ray absorptiometry (DXA) at baseline and at 6 months. Among patients treated with kefir-fermented milk, the relationships between baseline turnover and 6 months changes in DXA-determined BMD were significantly improved. The serum β C-terminal telopeptide of type I collagen (β-CTX) in those with T-scores > -1 patients significantly decreased after three months treatment. The formation marker serum osteocalcin (OC) turned from negative to positive after 6 months, representing the effect of kefir treatment. Serum parathyroid hormone (PTH) increased significantly after treatment with kefir, but decreased significantly in the control group. PTH may promote bone remodeling after treatment with kefir for 6 months. In this pilot study, we concluded that kefir-fermented milk therapy was associated with short-term changes in turnover and greater 6-month increases in hip BMD among osteoporotic patients. ClinicalTrials.gov NCT02361372.

Hypertriglyceridemic rats fed high fat diet as a model of metabolic syndrome.

PubMed

Kaprinay, B; Lipták, B; Slovák, L; Švík, K; Knezl, V; Sotníková, R; Gáspárová, Z

2016-12-21

People with metabolic syndrome have higher risk of cardiovascular diseases then those without. The aim of the work was to investigate whether high fat diet administered to Prague hereditary hypertriglyceridemic (HTG) rats can induce signs of metabolic syndrome (MetS). Our results showed that HTG rats fed high fat diet (HTGch) had disturbed glucose metabolism and also lipid metabolism - increased serum triacylglycerols (TAG), total cholesterol (Ch), low-density lipoprotein-Ch (LDL-Ch), and decreased high-density lipoprotein-Ch (HDL-Ch). Their livers proved markers of developing steatosis. Moreover, HTGch had increased blood pressure, yet the vascular endothelium was not significantly damaged. All these changes were accompanied with oxidative stress and tissue damage identified as increased liver concentrations of thiobarbituric acid reactive substances (TBARS) and activity of the lysosomal enzyme N-acetyl-D-glucosaminidase (NAGA). We assume that the model used may be suitable for the study of MetS with no evidence of obesity. Prolongation of the high fat diet duration might have a major impact on all parameters tested, especially on vascular endothelial function.

Effects of Active Mastication on Chronic Stress-Induced Bone Loss in Mice

PubMed Central

Azuma, Kagaku; Furuzawa, Manabu; Fujiwara, Shu; Yamada, Kumiko; Kubo, Kin-ya

2015-01-01

Chronic psychologic stress increases corticosterone levels, which decreases bone density. Active mastication or chewing attenuates stress-induced increases in corticosterone. We evaluated whether active mastication attenuates chronic stress-induced bone loss in mice. Male C57BL/6 (B6) mice were randomly divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube (60 min, 2x/day, 4 weeks). The stress/chewing group was given a wooden stick to chew during the experimental period. Quantitative micro-computed tomography, histologic analysis, and biochemical markers were used to evaluate the bone response. The stress/chewing group exhibited significantly attenuated stress-induced increases in serum corticosterone levels, suppressed bone formation, enhanced bone resorption, and decreased trabecular bone mass in the vertebrae and distal femurs, compared with mice in the stress group. Active mastication during exposure to chronic stress alleviated chronic stress-induced bone density loss in B6 mice. Active mastication during chronic psychologic stress may thus be an effective strategy to prevent and/or treat chronic stress-related osteopenia. PMID:26664256

Effects of Active Mastication on Chronic Stress-Induced Bone Loss in Mice.

PubMed

Azuma, Kagaku; Furuzawa, Manabu; Fujiwara, Shu; Yamada, Kumiko; Kubo, Kin-ya

2015-01-01

Chronic psychologic stress increases corticosterone levels, which decreases bone density. Active mastication or chewing attenuates stress-induced increases in corticosterone. We evaluated whether active mastication attenuates chronic stress-induced bone loss in mice. Male C57BL/6 (B6) mice were randomly divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube (60 min, 2x/day, 4 weeks). The stress/chewing group was given a wooden stick to chew during the experimental period. Quantitative micro-computed tomography, histologic analysis, and biochemical markers were used to evaluate the bone response. The stress/chewing group exhibited significantly attenuated stress-induced increases in serum corticosterone levels, suppressed bone formation, enhanced bone resorption, and decreased trabecular bone mass in the vertebrae and distal femurs, compared with mice in the stress group. Active mastication during exposure to chronic stress alleviated chronic stress-induced bone density loss in B6 mice. Active mastication during chronic psychologic stress may thus be an effective strategy to prevent and/or treat chronic stress-related osteopenia.

An adaptive reconstruction for Lagrangian, direct-forcing, immersed-boundary methods

NASA Astrophysics Data System (ADS)

Posa, Antonio; Vanella, Marcos; Balaras, Elias

2017-12-01

Lagrangian, direct-forcing, immersed boundary (IB) methods have been receiving increased attention due to their robustness in complex fluid-structure interaction problems. They are very sensitive, however, on the selection of the Lagrangian grid, which is typically used to define a solid or flexible body immersed in a fluid flow. In the present work we propose a cost-efficient solution to this problem without compromising accuracy. Central to our approach is the use of isoparametric mapping to bridge the relative resolution requirements of Lagrangian IB, and Eulerian grids. With this approach, the density of surface Lagrangian markers, which is essential to properly enforce boundary conditions, is adapted dynamically based on the characteristics of the underlying Eulerian grid. The markers are not stored and the Lagrangian data-structure is not modified. The proposed scheme is implemented in the framework of a moving least squares reconstruction formulation, but it can be adapted to any Lagrangian, direct-forcing formulation. The accuracy and robustness of the approach is demonstrated in a variety of test cases of increasing complexity.

Hyperpolarized xenon NMR and MRI signal amplification by gas extraction

PubMed Central

Zhou, Xin; Graziani, Dominic; Pines, Alexander

2009-01-01

A method is reported for enhancing the sensitivity of NMR of dissolved xenon by detecting the signal after extraction to the gas phase. We demonstrate hyperpolarized xenon signal amplification by gas extraction (Hyper-SAGE) in both NMR spectra and magnetic resonance images with time-of-flight information. Hyper-SAGE takes advantage of a change in physical phase to increase the density of polarized gas in the detection coil. At equilibrium, the concentration of gas-phase xenon is ≈10 times higher than that of the dissolved-phase gas. After extraction the xenon density can be further increased by several orders of magnitude by compression and/or liquefaction. Additionally, being a remote detection technique, the Hyper-SAGE effect is further enhanced in situations where the sample of interest would occupy only a small proportion of the traditional NMR receiver. Coupled with targeted xenon biosensors, Hyper-SAGE offers another path to highly sensitive molecular imaging of specific cell markers by detection of exhaled xenon gas. PMID:19805177

Short-term lower-body plyometric training improves whole body BMC, bone metabolic markers, and physical fitness in early pubertal male basketball players.

PubMed

Zribi, Anis; Zouch, Mohamed; Chaari, Hamada; Bouajina, Elyes; Ben Nasr, Hela; Zaouali, Monia; Tabka, Zouhair

2014-02-01

The effects of a 9-week lower-body plyometric training program on bone mass, bone markers and physical fitness was examined in 51 early pubertal male basketball players divided randomly into a plyometric group (PG: 25 participants) and a control group (CG: 26 participants). Areal bone mineral density (aBMD), bone mineral content (BMC), and bone area (BA) in the whole body, L2-L4 vertebrae, and in total hip, serum levels of osteocalcin (Oc) and C-terminal telopeptide fragment of Type I collagen (CTx), jump, sprint and power abilities were assessed at baseline and 9 weeks. Group comparisons were done by independent student's t-test between means and analyses of (ANOVA) and covariance (ANCOVA), adjusting for baseline values. PG experienced a significant increase in Oc (p < .01) and all physical fitness except for the 5-jump test. However, there was no improvement in aBMD, BMC and BA in any measured site, except in whole body BMC of the PG. A positive correlation was observed between percentage increase (Δ%) of physical fitness and those of (Oc) for the PG. In summary, biweekly sessions of lower body plyometric training program were successful for improving whole body BMC, bone formation marker (Oc) and physical fitness in early pubertal male basketball players.

A Phenotypic Change But Not Proliferation Underlies Glial Responses in Alzheimer Disease

PubMed Central

Serrano-Pozo, Alberto; Gómez-Isla, Teresa; Growdon, John H.; Frosch, Matthew P.; Hyman, Bradley T.

2014-01-01

Classical immunohistochemical studies in the Alzheimer disease (AD) brain reveal prominent glial reactions, but whether this pathological feature is due primarily to cell proliferation or to a phenotypic change of existing resting cells remains controversial. We performed double-fluorescence immunohistochemical studies of astrocytes and microglia, followed by unbiased stereology-based quantitation in temporal cortex of 40 AD patients and 32 age-matched nondemented subjects. Glial fibrillary acidic protein (GFAP) and major histocompatibility complex II (MHC2) were used as markers of astrocytic and microglial activation, respectively. Aldehyde dehydrogenase 1 L1 and glutamine synthetase were used as constitutive astrocytic markers, and ionized calcium-binding adaptor molecule 1 (IBA1) as a constitutive microglial marker. As expected, AD patients had higher numbers of GFAP+ astrocytes and MHC2+ microglia than the nondemented subjects. However, both groups had similar numbers of total astrocytes and microglia and, in the AD group, these total numbers remained essentially constant over the clinical course of the disease. The GFAP immunoreactivity of astrocytes, but not the MHC2 immunoreactivity of microglia, increased in parallel with the duration of the clinical illness in the AD group. Cortical atrophy contributed to the perception of increased glia density. We conclude that a phenotypic change of existing glial cells, rather than a marked proliferation of glial precursors, accounts for the majority of the glial responses observed in the AD brain. PMID:23602650

Treatment of bone loss in osteopenic patients with Crohn's disease: a double-blind, randomised trial of oral risedronate 35 mg once weekly or placebo, concomitant with calcium and vitamin D supplementation.

PubMed

van Bodegraven, Ad A; Bravenboer, Nathalie; Witte, Birgit I; Dijkstra, Gerard; van der Woude, C Janneke; Stokkers, Pieter C M; Russel, Maurice G; Oldenburg, Bas; Pierik, Marieke; Roos, Jan C; van Hogezand, Ruud A; Dik, Vincent K; Oostlander, Angela E; Netelenbos, J Coen; van de Langerijt, Lex; Hommes, Daniel W; Lips, Paul

2014-09-01

Osteoporosis and fractures are frequently encountered in patients with Crohn's disease. In order to prevent fractures, treatment with bone protecting drugs appears warranted early in the course of bone disease when bone loss is not yet prominent. We therefore aimed to demonstrate a beneficial effect on bone density of the bisphosphonate risedronate in osteopenic Crohn's disease patients. This double-blind, placebo-controlled randomised trial of risedronate with calcium and vitamin D supplementation was performed in osteopenic Crohn's disease patients. Patients were treated for 2 years with follow-up after 3 and after every 6 months. Disease characteristics and activity and bone turnover markers were assessed at all visits; dual x-ray absorptiometry was performed at baseline, 12 and 24 months; radiographs of the spine at baseline and 24 months. Of 132 consenting patients, 131 were randomised (67 placebo and 64 risedronate). Patient characteristics were similar in both groups, although the risedronate group was slightly heavier (body mass index 24.3 vs 23.0 kg/m(2)). Bone mineral density at lumbar spine increased 0.04 g/cm(2) on average in the risedronate group versus 0.01 g/cm(2) in the placebo group (p=0.007). The mean increase in total hip bone mineral density was 0.03 versus 0.01 g/cm(2), respectively (p=0.071). Fracture prevalence and incidence were similar. Change of T-scores and concentrations of bone turnover markers were consistent with a beneficial effect of risedronate when compared with placebo. The effect of risedronate was primarily demonstrated in the first 12 months of treatment. No serious unexpected suspected adverse events were observed. A 24-month treatment course with risedronate 35 mg once weekly, concomitant with calcium and vitamin D supplementation, in osteopenic Crohn's disease patients improved bone density at lumbar spine. NTR 163 Dutch Trial Register. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A high density integrated genetic linkage map of soybean and the development of a 1,536 Universal Soy Linkage Panel for QTL mapping

USDA-ARS?s Scientific Manuscript database

Single nucleotide polymorphisms (SNPs) are the marker of choice for many researchers due to their abundance and the high-throughput methods available for their multiplex analysis. Only recently have SNP markers been available to researchers in soybean [Glycine max (L.) Merr.] with the release of th...

Probability density function of a puff dispersing from the wall of a turbulent channel

NASA Astrophysics Data System (ADS)

Nguyen, Quoc; Papavassiliou, Dimitrios

2015-11-01

Study of dispersion of passive contaminants in turbulence has proved to be helpful in understanding fundamental heat and mass transfer phenomena. Many simulation and experimental works have been carried out to locate and track motions of scalar markers in a flow. One method is to combine Direct Numerical Simulation (DNS) and Lagrangian Scalar Tracking (LST) to record locations of markers. While this has proved to be useful, high computational cost remains a concern. In this study, we develop a model that could reproduce results obtained by DNS and LST for turbulent flow. Puffs of markers with different Schmidt numbers were released into a flow field at a frictional Reynolds number of 150. The point of release was at the channel wall, so that both diffusion and convection contribute to the puff dispersion pattern, defining different stages of dispersion. Based on outputs from DNS and LST, we seek the most suitable and feasible probability density function (PDF) that represents distribution of markers in the flow field. The PDF would play a significant role in predicting heat and mass transfer in wall turbulence, and would prove to be helpful where DNS and LST are not always available.

Systematic Review of Anthocyanins and Markers of Cardiovascular Disease.

PubMed

Wallace, Taylor C; Slavin, Margaret; Frankenfeld, Cara L

2016-01-09

Anthocyanins are dietary flavonoids commonly consumed in the diet, which have been suggested to have a preventative effect on cardiovascular disease (CVD) development among epidemiological studies. We systematically reviewed randomized controlled trials (RCTs) testing the effects of purified anthocyanins and anthocyanin-rich extracts on markers of CVD (triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and blood pressure) in both healthy and diseased populations. Eligible studies included RCTs of adults published in English. We searched PubMed, Web of Science Core Collection, and BIOSIS Previews for relevant articles from inception until 1 July 2014. Twelve RCTs representing 10 studies were included in this review. Supplementation with anthocyanins significantly improved LDL cholesterol among diseased individuals or those with elevated biomarkers. Supplementation did not significantly affect other markers of CVD in either healthy individuals or those with elevated markers. No adverse effects of anthocyanins were reported across studies at levels up to 640 mg/day. Limitations of trials in the qualitative analyses include short trial duration and large variability in the dose administered within the trials. Longer-duration trials assessing dose response are needed to adequately determine whether an effect of supplementation exists.

Role of Paraoxonase 1 Activity and Oxidative/Antioxidative Stress Markers in Patients with Acute Cerebral Infarction.

PubMed

Zhu, Hui; Zhao, Teng; Liu, Jingyao

2018-06-01

Paraoxonase1 (PON1) is an antioxidant which confers antioxidant properties to high-density lipoprotein (HDL) and prevents low-density lipoprotein (LDL) oxidation. The purpose of this study was to evaluate the activities of PON1 and oxidative/antioxidative stress markers in acute cerebral infarction. In this study, 161 patients diagnosed with acute cerebral infarction and 161 gender- and age-matched healthy controls were recruited. Based on the clinicoradiological profiles, the patients were further classified into two groups: lacunar infarction group and large-artery atherosclerosis group. We measured the individual lipid status parameters, oxidative and antioxidative stress status parameters, and PON1 activity. Serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and oxidative stress parameters in patients with acute cerebral infarction were significantly higher than those in the normal controls (p < 0.05). High-density lipoprotein cholesterol (HDL-C) level, PON1 activity, superoxide dismutase (SOD) activity, and antioxidative stress parameters in patients were lower than in the normal controls (p < 0.05). Superoxide anion (O2-), malondialdehyde (MDA), and PON1 levels in the lacunar infarction group were lower than in the large-artery atherosclerosis group (p < 0.05). Oxidative stress markers and PON1 activity are sensitive indicators of acute cerebral infarction. Our findings suggest a severely impaired antioxidative protection mechanism in these patients. Our study provides new insights into the pathophysiological mechanisms of acute cerebral infarction, which may also provide new therapeutic targets for ischemic cerebrovascular diseases.

Uneven distribution of expressed sequence tag loci on maize pachytene chromosomes

PubMed Central

Anderson, Lorinda K.; Lai, Ann; Stack, Stephen M.; Rizzon, Carene; Gaut, Brandon S.

2006-01-01

Examining the relationships among DNA sequence, meiotic recombination, and chromosome structure at a genome-wide scale has been difficult because only a few markers connect genetic linkage maps with physical maps. Here, we have positioned 1195 genetically mapped expressed sequence tag (EST) markers onto the 10 pachytene chromosomes of maize by using a newly developed resource, the RN-cM map. The RN-cM map charts the distribution of crossing over in the form of recombination nodules (RNs) along synaptonemal complexes (SCs, pachytene chromosomes) and allows genetic cM distances to be converted into physical micrometer distances on chromosomes. When this conversion is made, most of the EST markers used in the study are located distally on the chromosomes in euchromatin. ESTs are significantly clustered on chromosomes, even when only euchromatic chromosomal segments are considered. Gene density and recombination rate (as measured by EST and RN frequencies, respectively) are strongly correlated. However, crossover frequencies for telomeric intervals are much higher than was expected from their EST frequencies. For pachytene chromosomes, EST density is about fourfold higher in euchromatin compared with heterochromatin, while DNA density is 1.4 times higher in heterochromatin than in euchromatin. Based on DNA density values and the fraction of pachytene chromosome length that is euchromatic, we estimate that ∼1500 Mbp of the maize genome is in euchromatin. This overview of the organization of the maize genome will be useful in examining genome and chromosome evolution in plants. PMID:16339046

Potential Mechanisms Leading to the Abnormal Lipid Profile in Patients With Rheumatoid Arthritis Versus Healthy Volunteers and Reversal by Tofacitinib†, ‡

PubMed Central

Fleischmann, Roy; Davignon, Jean; Schwartz, Howard; Turner, Scott M.; Beysen, Carine; Milad, Mark; Hellerstein, Marc K.; Luo, Zhen; Kaplan, Irina V.; Riese, Richard; Zuckerman, Andrea; McInnes, Iain B.

2015-01-01

Objective Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). Systemic inflammation is proposed to play a fundamental role in the altered lipid metabolism associated with RA; however, the underlying mechanisms are unknown. We undertook this study to compare cholesterol and lipoprotein kinetics in patients with active RA with those in matched healthy volunteers. Methods This was a phase I open‐label mechanism‐of‐action study. Cholesterol and lipoprotein kinetics were assessed with 13C‐cholesterol and 13C‐leucine infusions. RA patients were reevaluated after receiving oral tofacitinib 10 mg twice daily for 6 weeks. Results Levels of high‐density lipoprotein (HDL) cholesterol, low‐density lipoprotein (LDL) cholesterol, total cholesterol, and apolipoprotein A‐I (Apo A‐I) as well as HDL cholesterol particle number were lower in RA patients (n = 36) than in healthy volunteers (n = 33). In contrast, the cholesterol ester fractional catabolic rate was higher in RA patients, but no differences were observed in cholesterol ester transfer protein, cholesterol ester production rate, HDL‐associated Apo A‐I fractional catabolic rate, or LDL‐associated Apo B fractional catabolic rate. Following tofacitinib treatment in RA patients, the cholesterol ester fractional catabolic rate decreased and cholesterol levels increased. The decrease in cholesterol ester fractional catabolic rate correlated significantly with the increase in HDL cholesterol. Additionally, HDL cholesterol particle number increased and markers of HDL cholesterol function improved. Conclusion This is the first study to assess cholesterol and lipoprotein kinetics in patients with active RA and matched healthy volunteers. The data suggest that low cholesterol levels in patients with active RA may be driven by increases in cholesterol ester catabolism. Tofacitinib treatment reduced cholesterol ester catabolism, thereby increasing cholesterol levels toward those in healthy volunteers, and markers of antiatherogenic HDL function improved. PMID:25470338

Effect of whole-body vibration on bone properties in aging mice.

PubMed

Wenger, Karl H; Freeman, James D; Fulzele, Sadanand; Immel, David M; Powell, Brian D; Molitor, Patrick; Chao, Yuh J; Gao, Hong-Sheng; Elsalanty, Mohammed; Hamrick, Mark W; Isales, Carlos M; Yu, Jack C

2010-10-01

Recent studies suggest that whole-body vibration (WBV) can improve measures of bone health for certain clinical conditions and ages. In the elderly, there also is particular interest in assessing the ability of physical interventions such as WBV to improve coordination, strength, and movement speed, which help prevent falls and fractures and maintain ambulation for independent living. The current study evaluated the efficacy of WBV in an aging mouse model. Two levels of vibration--0.5 and 1.5g--were applied at 32Hz to CB57BL/6 male mice (n=9 each) beginning at age 18 months and continuing for 12 weeks, 30 min/day, in a novel pivoting vibration device. Previous reports indicate that bone parameters in these mice begin to decrease substantially at 18 months, equivalent to mid-fifties for humans. Micro-computed tomography (micro-CT) and biomechanical assessments were made in the femur, radius, and lumbar vertebra to determine the effect of these WBV magnitudes and durations in the aging model. Sera also were collected for analysis of bone formation and breakdown markers. Mineralizing surface and cell counts were determined histologically. Bone volume in four regions of the femur did not change significantly, but there was a consistent shift toward higher mean density in the bone density spectrum (BDS), with the two vibration levels producing similar results. This new parameter represents an integral of the conventional density histogram. The amount of high density bone statistically improved in the head, neck, and diaphysis. Biomechanically, there was a trend toward greater stiffness in the 1.5 g group (p=0.139 vs. controls in the radius), and no change in strength. In the lumbar spine, no differences were seen due to vibration. Both vibration groups significantly reduced pyridinoline crosslinks, a collagen breakdown marker. They also significantly increased dynamic mineralization, MS/BS. Furthermore, osteoclasts were most numerous in the 1.5 g group (p≤ 0.05). These findings suggest that some benefits of WBV found in previous studies of young and mature rodent models may extend to an aging population. Density parameters indicated 0.5 g was more effective than 1.5 g. Serological markers, by contrast, favored 1.5 g, while biomechanically and histologically the results were mixed. Although the purported anabolic effect of WBV on bone homeostasis may depend on location and the parameter of interest, this emerging therapy at a minimum does not appear to compromise bone health by the measures studied here. Copyright © 2010 Elsevier Inc. All rights reserved.

Blood lipids, infection, and inflammatory markers in the Tsimane of Bolivia.

PubMed

Vasunilashorn, Sarinnapha; Crimmins, Eileen M; Kim, Jung Ki; Winking, Jeff; Gurven, Michael; Kaplan, Hillard; Finch, Caleb E

2010-01-01

Little is known about blood cholesterol (blood-C) levels under conditions of infection and limited diet. This study examines blood-C and markers of infection and inflammation in the Tsimane of the Bolivian Amazon, indigenous forager farmers living in conditions that model preindustrial European populations by their short life expectancy, high load of infections and inflammation, and limited diets. We use multivariate models to determine the relationships between lipid levels and markers of infection and inflammation. Adult Tsimane (N = 418, age 20-84) were characterized for blood lipids, cells, and inflammatory markers in relation to individual loads of parasites and village region. Most of the Tsimane (60%) carried at least one parasite species, averaging 1.3 species per person. Serum high-density lipoprotein cholesterol (HDL-C), total cholesterol (total-C), and low-density lipoprotein cholesterol (LDL-C) were below the U.S. norms and varied inversely with markers of infection and inflammation: C-reactive protein (CRP), interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), immunoglobulin (Ig) E and eosinophil count. Although no relationship of parasite load to blood-C was found, there was an association between anemia and parasite prevalence. We conclude that the highly infected environment of the Tsimane is related to low levels of blood total-C, HDL-C, and LDL-C. This may suggest a potential reason why arterial disease is largely absent in the Tsimane. © 2010 Wiley-Liss, Inc.

Surface receptors on human haematopoietic cell lines.

PubMed Central

Huber, C; Sundström, C; Nilsson, K; Wigzell, H

1976-01-01

The expression of complement receptors, of Fc receptors, of SRBC receptors and of S-Ig was investigated on human haematopoietic cell lines of proved malignant derivation. According to their origin and to a panel of phenotypic markers these lines have been classified into lymphoma lines, myeloma lines and leukemia lines. Results were compared with those obtained on non-malignant EBV carrying lymphoblastoid cell lines (LCL). Among the lymphoid cell lines the LCL showed a pattern of B-lymphocyte surface markers, i.e. surface immunoglobulins, C3 receptors but low density of Fc receptors. The non-Burkitt lymphoma lines bore in varying degree these B-lymphocyte markers. The lines U-698 M and DG-75 were exceptional in having only surface immunoglobulin. The Burkitt lymphoma lines had all B-lymphocyte markers. The myeloma lines differed from the lymphoid lines in lacking C3 and Fc receptors and showed only trace amounts of surface immunoglobulins. In contrast to lymphoid and myeloma lines, the leukaemia lines were completely lacking surface immunoglobulins, but showed C3 and Fc receptors in variable densities. On line, the ALL derived line MOLT-3 showed the capacity to spontaneous rosette formation with SRBC. The findings that LCL presented a homogeneous pattern of B-lymphocyte surface markers may be of value in order to discriminate between these lines and lines derived from haematopoietic malignancies other than Burkitt lymphomas. PMID:963908

Levels of high-density lipoprotein cholesterol (HDL-C) among children with steady-state sickle cell disease

PubMed Central

2010-01-01

Background The search for sickle cell disease (SCD) prognosis biomarkers is a challenge. These markers identification can help to establish further therapy, later severe clinical complications and with patients follow-up. We attempted to study a possible involvement of levels of high-density lipoprotein cholesterol (HDL-C) in steady-state children with SCD, once that this lipid marker has been correlated with anti-inflammatory, anti-oxidative, anti-aggregation, anti-coagulant and pro-fibrinolytic activities, important aspects to be considered in sickle cell disease pathogenesis. Methods We prospectively analyzed biochemical, inflammatory and hematological biomarkers of 152 steady-state infants with SCD and 132 healthy subjects using immunochemistry, immunoassay and electronic cell counter respectively. Clinical data were collected from patient medical records. Results Of the 152 infants investigated had a significant positive association of high-density lipoprotein cholesterol with hemoglobin (P < 0.001), hematocrit (P < 0.001) and total cholesterol (P < 0.001) and a negative significant association with reticulocytes (P = 0.046), leukocytes (P = 0.015), monocytes (P = 0.004) and platelets (P = 0.005), bilirubins [total bilirubin (P < 0.001), direct bilirubin (P < 0.001) and indirect bilirubin (P < 0.001], iron (P < 0.001), aminotransferases [aspartate aminotransferase (P = 0.004), alanine aminotransferase (P = 0.035)], lactate dehydrogenase (P < 0.001), urea (P = 0.030), alpha 1-antitrypsin (P < 0.001), very low-density lipoprotein cholesterol (P = 0.003), triglycerides (P = 0.005) and hemoglobin S (P = 0.002). Low high-density lipoprotein cholesterol concentration was associated with the history of cardiac abnormalities (P = 0.025), pneumonia (P = 0.033) and blood transfusion use (P = 0.025). Lipids and inflammatory markers were associated with the presence of cholelithiasis. Conclusions We hypothesize that some SCD patients can have a specific dyslipidemic subphenotype characterized by low HDL-C with hypertriglyceridemia and high VLDL-C in association with other biomarkers, including those related to inflammation. This represents an important step toward a more reliable clinical prognosis. Additional studies are warranted to test this hypothesis and the probably mechanisms involved in this complex network of markers and their role in SCD pathogenesis. PMID:20799970

Sustaining hypercitrullinemia, hypercholesterolemia and augmented oxidative stress in Japanese children with aspartate/glutamate carrier isoform 2-citrin-deficiency even during the silent period.

PubMed

Nagasaka, Hironori; Okano, Yoshiyuki; Tsukahara, Hirokazu; Shigematsu, Yosuke; Momoi, Toru; Yorifuji, Junko; Miida, Takashi; Ohura, Toshihiro; Kobayashi, Keiko; Saheki, Takeyori; Hirano, Kenichi; Takayanagi, Masaki; Yorifuji, Tohru

2009-05-01

Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) shows diverse metabolic abnormalities such as urea cycle dysfunction together with citrullinemia, galactosemia, and suppressed gluconeogenesis. Such abnormalities apparently resolve during the first year of life. However, metabolic profiles of the silent period remain unknown. We analyzed oxidative stress markers and profiles of amino acids, carbohydrates, and lipids in 20 asymptomatic children with aspartate/glutamate carrier isoform 2-citrin-deficiency aged 1-10 years, for whom tests showed normal liver function. Despite normal plasma ammonia levels, the affected children showed higher blood levels of ornithine (p<0.001) and citrulline (p<0.01)--amino acids involved in the urea cycle--than healthy children. Blood levels of nitrite/nitrate, metabolites of nitric oxide (NO), and asymmetric dimethylarginine inhibiting NO production from arginine were not different between these two groups. Blood glucose, galactose, pyruvate, and lactate levels after 4-5h fasting were not different between these groups, but the affected group showed a significantly higher lactate to pyruvate ratio. Low-density and high-density lipoprotein cholesterol levels in the affected group were 1.5 times higher than those in the controls. Plasma oxidized low-density lipoprotein apparently increased in the affected children; their levels of urinary oxidative stress markers such as 8-hydroxy-2'-deoxyguanosine and acrolein-lysine were significantly higher than those in the controls. Results of this study showed, even during the silent period, sustained hypercitrullinemia, hypercholesterolemia, and augmented oxidative stress in children with citrin deficiency.

Neighbourhood walkability, road density and socio-economic status in Sydney, Australia.

PubMed

Cowie, Christine T; Ding, Ding; Rolfe, Margaret I; Mayne, Darren J; Jalaludin, Bin; Bauman, Adrian; Morgan, Geoffrey G

2016-04-27

Planning and transport agencies play a vital role in influencing the design of townscapes, travel modes and travel behaviors, which in turn impact on the walkability of neighbourhoods and residents' physical activity opportunities. Optimising neighbourhood walkability is desirable in built environments, however, the population health benefits of walkability may be offset by increased exposure to traffic related air pollution. This paper describes the spatial distribution of neighbourhood walkability and weighted road density, a marker for traffic related air pollution, in Sydney, Australia. As exposure to air pollution is related to socio-economic status in some cities, this paper also examines the spatial distribution of weighted road density and walkability by socio-economic status (SES). We calculated walkability, weighted road density (as a measure of traffic related air pollution) and SES, using predefined and validated measures, for 5858 Sydney neighbourhoods, representing 3.6 million population. We overlaid tertiles of walkability and weighted road density to define "sweet-spots" (high walkability-low weighted road density), and "sour- spots" (low walkability-high weighted road density) neighbourhoods. We also examined the distribution of walkability and weighted road density by SES quintiles. Walkability and weighted road density showed a clear east-west gradient across the region. Our study found that only 4 % of Sydney's population lived in sweet-spot" neighbourhoods with high walkability and low weighted road density (desirable), and these tended to be located closer to the city centre. A greater proportion of neighbourhoods had health limiting attributes of high weighted road density or low walkability (about 20 % each), and over 5 % of the population lived in "sour-spot" neighbourhoods with low walkability and high weighted road density (least desirable). These neighbourhoods were more distant from the city centre and scattered more widely. There were no linear trends between walkability/weighted road density and neighbourhood SES. Our walkability and weighted road density maps and associated analyses by SES can help identify neighbourhoods with inequalities in health-promoting or health-limiting environments. Planning agencies should seek out opportunities for increased neighbourhood walkability through improved urban development and transport planning, which simultaneously minimizes exposure to traffic related air pollution.

[Long-term effects of 7-year growth hormone substitution on bone metabolism, bone density, and bone quality in growth hormone-deficient adults].

PubMed

Wilhelm, Birgit; Kann, Peter Herbert

2004-10-15

Subnormal bone mineral density (BMD) and increased fracture risk are described in patients with growth hormone deficiency (GHD). Growth hormone (GH) has been reported to have beneficial effects on bone in GHD. The aim of this study was to investigate the long-term effects of GH replacement therapy on bone metabolism, BMD, and bone quality in patients with GHD. 20 adult patients with GHD (eleven male, nine female, mean age 42.5 years) were included in the study and randomized to either GH or placebo in a dose of 0.25 U/kg body weight/week. After 6 months all patients received GH. After a 1-year double-blind, placebo-controlled study the patients were followed for another 72 months in an open study. The patients were compared to 20 age- und sex-matched healthy controls. Bone turnover was determined by ICTP (type I collagen carboxyterminal cross-linked telopeptide) as parameter of bone resorption and PICP (carboxyterminal propeptide of type I procollagen) as marker of bone formation. BMD was measured at the lumbar spine by dual-photon absorptiometry (DPA) and at the forearm by single-photon absorptiometry (SPA). Apparent phalangeal ultrasound transmission velocity (APU) was assessed as parameter of bone quality independent of BMD. At the beginning of the study BMD at both measuring sites was lower in patients with GHD than in healthy controls. During the 1st year of GH replacement therapy BMD decreased, followed by a continuous increase in BMD (about 12%) up to 60 months which remained unchanged thereafter, building up a plateau. After 72 months no significant difference between the patients and the healthy controls could be detected. Concerning parameters of bone turnover, first ICTP as marker of bone resorption showed a significant increase, later on the marker of bone formation increased as well. APU decreased during the first 6 months of treatment, but had returned to its baseline value after 24 months and remained unchanged throughout the rest of the study. BMD is subnormal in adults with GHD. GH replacement therapy stimulates bone turnover in patients with GHD and in the long term such stimulation results in an increased BMD. Thereby, GH shows a triphasic action on BMD: an initial decrease in BMD during the 1st year, followed by a continuous increase in BMD with buildup of a stable plateau after 60 months. The newly formed bone seems to have normal bone elasticity.

Construction of a high-density genetic map for grape using specific length amplified fragment (SLAF) sequencing

PubMed Central

Guo, Yinshan; Xing, Huiyang; Zhao, Yuhui; Liu, Zhendong; Li, Kun; Guo, Xiuwu

2017-01-01

Genetic maps are important tools in plant genomics and breeding. We report a large-scale discovery of single nucleotide polymorphisms (SNPs) using the specific length amplified fragment sequencing (SLAF-seq) technique for the construction of high-density genetic maps for two elite wine grape cultivars, ‘Chardonnay’ and ‘Beibinghong’, and their 130 F1 plants. A total of 372.53 M paired-end reads were obtained after preprocessing. The average sequencing depth was 33.81 for ‘Chardonnay’ (the female parent), 48.20 for ‘Beibinghong’ (the male parent), and 12.66 for the F1 offspring. We detected 202,349 high-quality SLAFs of which 144,972 were polymorphic; 10,042 SNPs were used to construct a genetic map that spanned 1,969.95 cM, with an average genetic distance of 0.23 cM between adjacent markers. This genetic map contains the largest molecular marker number of the grape maps so far reported. We thus demonstrate that SLAF-seq is a promising strategy for the construction of high-density genetic maps; the map that we report here is a good potential resource for QTL mapping of genes linked to major economic and agronomic traits, map-based cloning, and marker-assisted selection of grape. PMID:28746364

Properties of different density genotypes used in dairy cattle evaluation

USDA-ARS?s Scientific Manuscript database

Dairy cattle breeders have used a 50K chip since April 2008 and a less expensive, lower density (3K) chip since September 2010 in genomic selection. Evaluations from 3K are less reliable because genotype calls are less accurate and missing markers are imputed. After excluding genotypes with < 90% ca...

Development and validation of a low-density SNP panel related to prolificacy in sheep

USDA-ARS?s Scientific Manuscript database

High-density SNP panels (e.g., 50,000 and 600,000 markers) have been used in exploratory population genetic studies with commercial and minor breeds of sheep. However, routine genetic diversity evaluations of large numbers of samples with large panels are in general cost-prohibitive for gene banks. ...

Enhanced osteoprogenitor elongated collagen fiber matrix formation by bioactive glass ionic silicon dependent on Sp7 (osterix) transcription.

PubMed

Varanasi, Venu G; Odatsu, Tetsurou; Bishop, Timothy; Chang, Joyce; Owyoung, Jeremy; Loomer, Peter M

2016-10-01

Bioactive glasses release ions, those enhance osteoblast collagen matrix synthesis and osteogenic marker expression during bone healing. Collagen matrix density and osteogenic marker expression depend on osteogenic transcription factors, (e.g., Osterix (OSX)). We hypothesize that enhanced expression and formation of collagen by Si(4+) depends on enhanced expression of OSX transcription. Experimental bioactive glass (6P53-b) and commercial Bioglass(TM) (45S5) were dissolved in basal medium to make glass conditioned medium (GCM). ICP-MS analysis was used to measure bioactive glass ion release rates. MC3T3-E1 cells were cultured for 20 days, and gene expression and extracellular matrix collagen formation was analyzed. In a separate study, siRNA was used to determine the effect of OSX knockdown on impacting the effect of Si(4+) on osteogenic markers and matrix collagen formation. Each bioactive glass exhibited similar ion release rates for all ions, except Mg(2+) released by 6P53-b. Gene expression results showed that GCM markedly enhanced many osteogenic markers, and 45S5 GCM showed higher levels of expression and collagen matrix fiber bundle density than 6P53-b GCM. Upon knockdown of OSX transcription, collagen type 5, alkaline phosphatase, and matrix density were not enhanced as compared to wild type cells. This study illustrates that the enhancement of elongated collagen fiber matrix formation by Si(±) depends on OSX transcription. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2604-2615, 2016. © 2016 Wiley Periodicals, Inc.

A Saturated Genetic Linkage Map of Autotetraploid Alfalfa (Medicago sativa L.) Developed Using Genotyping-by-Sequencing Is Highly Syntenous with the Medicago truncatula Genome

PubMed Central

Li, Xuehui; Wei, Yanling; Acharya, Ananta; Jiang, Qingzhen; Kang, Junmei; Brummer, E. Charles

2014-01-01

A genetic linkage map is a valuable tool for quantitative trait locus mapping, map-based gene cloning, comparative mapping, and whole-genome assembly. Alfalfa, one of the most important forage crops in the world, is autotetraploid, allogamous, and highly heterozygous, characteristics that have impeded the construction of a high-density linkage map using traditional genetic marker systems. Using genotyping-by-sequencing (GBS), we constructed low-cost, reasonably high-density linkage maps for both maternal and paternal parental genomes of an autotetraploid alfalfa F1 population. The resulting maps contain 3591 single-nucleotide polymorphism markers on 64 linkage groups across both parents, with an average density of one marker per 1.5 and 1.0 cM for the maternal and paternal haplotype maps, respectively. Chromosome assignments were made based on homology of markers to the M. truncatula genome. Four linkage groups representing the four haplotypes of each alfalfa chromosome were assigned to each of the eight Medicago chromosomes in both the maternal and paternal parents. The alfalfa linkage groups were highly syntenous with M. truncatula, and clearly identified the known translocation between Chromosomes 4 and 8. In addition, a small inversion on Chromosome 1 was identified between M. truncatula and M. sativa. GBS enabled us to develop a saturated linkage map for alfalfa that greatly improved genome coverage relative to previous maps and that will facilitate investigation of genome structure. GBS could be used in breeding populations to accelerate molecular breeding in alfalfa. PMID:25147192

A saturated genetic linkage map of autotetraploid alfalfa (Medicago sativa L.) developed using genotyping-by-sequencing is highly syntenous with the Medicago truncatula genome.

PubMed

Li, Xuehui; Wei, Yanling; Acharya, Ananta; Jiang, Qingzhen; Kang, Junmei; Brummer, E Charles

2014-08-21

A genetic linkage map is a valuable tool for quantitative trait locus mapping, map-based gene cloning, comparative mapping, and whole-genome assembly. Alfalfa, one of the most important forage crops in the world, is autotetraploid, allogamous, and highly heterozygous, characteristics that have impeded the construction of a high-density linkage map using traditional genetic marker systems. Using genotyping-by-sequencing (GBS), we constructed low-cost, reasonably high-density linkage maps for both maternal and paternal parental genomes of an autotetraploid alfalfa F1 population. The resulting maps contain 3591 single-nucleotide polymorphism markers on 64 linkage groups across both parents, with an average density of one marker per 1.5 and 1.0 cM for the maternal and paternal haplotype maps, respectively. Chromosome assignments were made based on homology of markers to the M. truncatula genome. Four linkage groups representing the four haplotypes of each alfalfa chromosome were assigned to each of the eight Medicago chromosomes in both the maternal and paternal parents. The alfalfa linkage groups were highly syntenous with M. truncatula, and clearly identified the known translocation between Chromosomes 4 and 8. In addition, a small inversion on Chromosome 1 was identified between M. truncatula and M. sativa. GBS enabled us to develop a saturated linkage map for alfalfa that greatly improved genome coverage relative to previous maps and that will facilitate investigation of genome structure. GBS could be used in breeding populations to accelerate molecular breeding in alfalfa. Copyright © 2014 Li et al.

Effects of growth hormone therapy on bone density and fracture risk in age-related osteoporosis in the absence of growth hormone deficiency: a systematic review and meta-analysis.

PubMed

Barake, Maya; Arabi, Asma; Nakhoul, Nancy; El-Hajj Fuleihan, Ghada; El Ghandour, Sarah; Klibanski, Anne; Tritos, Nicholas A

2018-01-01

In adults, growth hormone deficiency (GHD) has been associated with low bone mineral density (BMD), an effect counteracted by growth hormone (GH) replacement. Whether GH is beneficial in adults with age-related bone loss and without hypopituitarism is unclear. We conducted a systematic literature search using Medline, Embase and the Cochrane Register of Controlled Trials. We extracted and analyzed data according to the bone outcome included [bone mineral content (BMC), BMD, and bone biomarker, fracture risk]. We performed a meta-analysis when possible. We included eight studies. Seven randomized 272 post-menopausal women, 61-69 years, to GH or control, for 6-24 months, and the eighth was an extension trial. Except for one study, all women received concurrent osteoporosis therapies. There was no significant effect of GH, as compared to control, on BMD at the lumbar spine (Weighted mean difference WMD = -0.01 [-0.04, 0.02]), total hip (WMD = 0 [-0.05, 0.06]) or femoral neck (WMD = 0 [-0.03, 0.04]). Similarly, no effect was seen on BMC. GH significantly increased the bone formation marker procollagen type-I carboxy-terminal propeptide (PICP) (WMD = 14.03 [2.68, 25.38]). GH resulted in a trend for increase in osteocalcin and in bone resorption markers. Patients who received GH had a significant decrease in fracture risk as compared to control (RR = 0.63 [0.46, 0.87]). Reported adverse events were not major, mostly related to fluid retention. GH may not improve bone density in women with age-related bone loss but may decrease fracture risk. Larger studies of longer duration are needed to further explore these findings in both genders, and to investigate the effect of GH on bone quality.

Massive nest-box supplementation boosts fecundity, survival and even immigration without altering mating and reproductive behaviour in a rapidly recovered bird population.

PubMed

Berthier, Karine; Leippert, Fabio; Fumagalli, Luca; Arlettaz, Raphaël

2012-01-01

Habitat restoration measures may result in artificially high breeding density, for instance when nest-boxes saturate the environment, which can negatively impact species' demography. Potential risks include changes in mating and reproductive behaviour such as increased extra-pair paternity, conspecific brood parasitism, and polygyny. Under particular cicumstances, these mechanisms may disrupt reproduction, with populations dragged into an extinction vortex. With the use of nuclear microsatellite markers, we investigated the occurrence of these potentially negative effects in a recovered population of a rare secondary cavity-nesting farmland bird of Central Europe, the hoopoe (Upupa epops). High intensity farming in the study area has resulted in a total eradication of cavity trees, depriving hoopoes from breeding sites. An intensive nest-box campaign rectified this problem, resulting in a spectacular population recovery within a few years only. There was some concern, however, that the new, high artificially-induced breeding density might alter hoopoe mating and reproductive behaviour. As the species underwent a serious demographic bottleneck in the 1970-1990s, we also used the microsatellite markers to reconstitute the demo-genetic history of the population, looking in particular for signs of genetic erosion. We found i) a low occurrence of extra-pair paternity, polygyny and conspecific brood parasitism, ii) a high level of neutral genetic diversity (mean number of alleles and expected heterozygosity per locus: 13.8 and 83%, respectively) and, iii) evidence for genetic connectivity through recent immigration of individuals from well differentiated populations. The recent increase in breeding density did thus not induce so far any noticeable detrimental changes in mating and reproductive behaviour. The demographic bottleneck undergone by the population in the 1970s-1990s was furthermore not accompanied by any significant drop in neutral genetic diversity. Finally, genetic data converged with a concomitant demographic study to evidence that immigration strongly contributed to local population recovery.

Skeletal Health After Continuation, Withdrawal, or Delay of Alendronate in Men With Prostate Cancer Undergoing Androgen-Deprivation Therapy

PubMed Central

Greenspan, Susan L.; Nelson, Joel B.; Trump, Donald L.; Wagner, Julie M.; Miller, Megan E.; Perera, Subashan; Resnick, Neil M.

2008-01-01

Purpose Androgen-deprivation therapy (ADT) for prostate cancer is associated with bone loss and osteoporotic fractures. Our objective was to examine changes in bone density and turnover with sustained, discontinued, or delayed oral bisphosphonate therapy in men receiving ADT. Patients and Methods A total of 112 men with nonmetastatic prostate cancer receiving ADT were randomly assigned to alendronate 70 mg once weekly or placebo in a double-blind, partial-crossover trial with a second random assignment at year 2 for those who initially received active therapy. Outcomes included bone mineral density and bone turnover markers. Results Men initially randomly assigned to alendronate and randomly reassigned at year 2 to continue had additional bone density gains at the spine (mean, 2.3% ± 0.7) and hip (mean, 1.3% ± 0.5%; both P < .01); those randomly assigned to placebo in year 2 maintained density at the spine and hip but lost (mean, −1.9% ± 0.6%; P < .01) at the forearm. Patients randomly assigned to begin alendronate in year 2 experienced improvements in bone mass at the spine and hip, but experienced less of an increase compared with those who initiated alendronate at baseline. Men receiving alendronate for 2 years experienced a mean 6.7% (± 1.2%) increase at the spine and a 3.2% (± 1.5%) at the hip (both P < .05). Bone turnover remained suppressed. Conclusion Among men with nonmetastatic prostate cancer receiving ADT, once-weekly alendronate improves bone density and decreases turnover. A second year of alendronate provides additional skeletal benefit, whereas discontinuation results in bone loss and increased bone turnover. Delay in bisphosphonate therapy appears detrimental to bone health. PMID:18802155

The Distribution of Intratumoral Macrophages Correlates with Molecular Phenotypes and Impacts Prognosis in Colorectal Carcinoma.

PubMed

Kim, Younghoon; Wen, Xianyu; Bae, Jeong Mo; Kim, Jung Ho; Cho, Nam-Yun; Kang, Gyeong Hoon

2018-06-15

The role of tumor-associated macrophages (TAMs) in colorectal cancer (CRC) remains elusive. In this study, we aimed to examine the correlation between TAMs, clinicopathological features, tumor-infiltrating lymphocytes (TILs), and prognosis in CRC via image analysis. Immunohistochemical staining for CD68 and CD163 was performed with pan-macrophage and M2-macrophage markers, respectively. Each marker was separately analyzed for intraepithelial and stromal area densities. All four macrophage densities showed a significant correlation with one another (p = 0.001). Intraepithelial CD68+ macrophage densities showed a correlation with pTNM stage (p = 0.008), microsatellite instability (p < 0.001), CpG island methylator phenotype (p < 0.001), and TIL densities (p < 0.001). Intraepithelial CD163+ macrophage densities were associated with perineural invasion, MSI, CIMP, and TIL densities (p < 0.001). Stromal CD68+ and CD163+ macrophage densities had a significant relationship with Intraepithelial and stromal CD3+ (p = 0.001 and p < 0.001, respectively) and CD8+ (p < 0.001) T cells. High intraepithelial CD68+ macrophage density was associated with worse overall survival (HR = 1.386, 95% CI = 1.043-1.843, p = 0.025) and progression-free survival (HR = 1.522, 95% CI = 1.146-2.020, p = 0.004). Intraepithelial CD68+ macrophage density was also an independent prognostic factor of the progression-free survival (HR = 1.447, 95% CI = 1.076-1.947, p = 0.015) of CRC patients regardless of pTNM stage, lymphatic, venous, and perineural invasions, and TIL densities. Our results indicate that the density of intratumoral macrophages are useful prognostic indicator for further stratifying T cell populations in CRC. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Proteomic Markers of Functional Sperm Population in Bovines: Comparison of Low- and High-Density Spermatozoa Following Cryopreservation.

PubMed

D'Amours, Olivier; Frenette, Gilles; Bourassa, Sylvie; Calvo, Ézéchiel; Blondin, Patrick; Sullivan, Robert

2018-01-05

Mammalian semen contains a heterogeneous population of sperm cells. This heterogeneity results from variability in the complex processes of cell differentiation in the testis, biochemical modifications undergone by spermatozoa during transit along the male reproductive tract, interactions with secretions from accessory sex glands at ejaculation, and, in the context of reproductive technologies, in the ability of ejaculated spermatozoa to resist damage associated with freeze-thaw procedures. When submitted to density gradient centrifugation, ejaculated spermatozoa distribute themselves into two distinct populations: a low-density population characterized by low motility parameters, and a high-density population with high motility characteristics. To understand the origin of ejaculated spermatozoa heterogeneity, cryopreserved semen samples from bulls used by the artificial insemination (A.I.) industry were submitted to Percoll gradient centrifugation. Proteins from low and high density spermatozoa were then extracted with sodium deoxycholate and submitted to proteomic analysis using iTRAQ (isobaric tag for relative and absolute quantitation) methodologies. Quantification of selected sperm proteins was confirmed by multiple reaction monitoring (MRM). Overall, 31 different proteins were more abundant in low-density spermatozoa, while 80 different proteins were more abundant in the high-density subpopulation. Proteins enriched in high-density spermatozoa were markers of sperm functionality such as the glycolytic process, binding to the egg zona pellucida, and motility. Low-density spermatozoa were not solely characterized by loss of proteins and their associated functions. Chaperonin-containing TCP1s and chaperones are hallmarks of the low-density subpopulation. iTRAQ analysis revealed that other proteins such as binder of sperm proteins, histone, GPX5, ELSPBP1, and clusterin are overexpressed in low-density spermatozoa suggesting that these proteins represent defects occurring at different steps during the sperm journey. These differences contribute to the sperm cell heterogeneity present in mammalian semen.

[Studies of marker screening efficiency and corresponding influencing factors in QTL composite interval mapping].

PubMed

Gao, Yong-Ming; Wan, Ping

2002-06-01

Screening markers efficiently is the foundation of mapping QTLs by composite interval mapping. Main and interaction markers distinguished, besides using background control for genetic variation, could also be used to construct intervals of two-way searching for mapping QTLs with epistasis, which can save a lot of calculation time. Therefore, the efficiency of marker screening would affect power and precision of QTL mapping. A doubled haploid population with 200 individuals and 5 chromosomes was constructed, with 50 markers evenly distributed at 10 cM space. Among a total of 6 QTLs, one was placed on chromosome I, two linked on chromosome II, and the other three linked on chromosome IV. QTL setting included additive effects and epistatic effects of additive x additive, the corresponding QTL interaction effects were set if data were collected under multiple environments. The heritability was assumed to be 0.5 if no special declaration. The power of marker screening by stepwise regression, forward regression, and three methods for random effect prediction, e.g. best linear unbiased prediction (BLUP), linear unbiased prediction (LUP) and adjusted unbiased prediction (AUP), was studied and compared through 100 Monte Carlo simulations. The results indicated that the marker screening power by stepwise regression at 0.1, 0.05 and 0.01 significant level changed from 2% to 68%, the power changed from 2% to 72% by forward regression. The larger the QTL effects, the higher the marker screening power. While the power of marker screening by three random effect prediction was very low, the maximum was only 13%. That suggested that regression methods were much better than those by using the approaches of random effect prediction to identify efficient markers flanking QTLs, and forward selection method was more simple and efficient. The results of simulation study on heritability showed that heightening of both general heritability and interaction heritability of genotype x environments could enhance marker screening power, the former had a greater influence on QTLs with larger main and/or epistatic effects, while the later on QTLs with small main and/or epistatic effects. The simulation of 100 times was also conducted to study the influence of different marker number and density on marker screening power. It is indicated that the marker screening power would decrease if there were too many markers, especially with high density in a mapping population, which suggested that a mapping population with definite individuals could only hold limited markers. According to the simulation study, the reasonable number of markers should not be more than individuals. The simulation study of marker screening under multiple environments showed high total power of marker screening. In order to relieve the problem that marker screening power restricted the efficiency of QTL mapping, markers identified in multiple environments could be used to construct two search intervals.

A resource of large-scale molecular markers for monitoring Agropyron cristatum chromatin introgression in wheat background based on transcriptome sequences.

PubMed

Zhang, Jinpeng; Liu, Weihua; Lu, Yuqing; Liu, Qunxing; Yang, Xinming; Li, Xiuquan; Li, Lihui

2017-09-20

Agropyron cristatum is a wild grass of the tribe Triticeae and serves as a gene donor for wheat improvement. However, very few markers can be used to monitor A. cristatum chromatin introgressions in wheat. Here, we reported a resource of large-scale molecular markers for tracking alien introgressions in wheat based on transcriptome sequences. By aligning A. cristatum unigenes with the Chinese Spring reference genome sequences, we designed 9602 A. cristatum expressed sequence tag-sequence-tagged site (EST-STS) markers for PCR amplification and experimental screening. As a result, 6063 polymorphic EST-STS markers were specific for the A. cristatum P genome in the single-receipt wheat background. A total of 4956 randomly selected polymorphic EST-STS markers were further tested in eight wheat variety backgrounds, and 3070 markers displaying stable and polymorphic amplification were validated. These markers covered more than 98% of the A. cristatum genome, and the marker distribution density was approximately 1.28 cM. An application case of all EST-STS markers was validated on the A. cristatum 6 P chromosome. These markers were successfully applied in the tracking of alien A. cristatum chromatin. Altogether, this study provided a universal method of large-scale molecular marker development to monitor wild relative chromatin in wheat.

Microsatellite analysis and marker development in garlic: distribution in EST sequence, genetic diversity analysis, and marker transferability across Alliaceae.

PubMed

Barboza, Karina; Beretta, Vanesa; Kozub, Perla C; Salinas, Cecilia; Morgenfeld, Mauro M; Galmarini, Claudio R; Cavagnaro, Pablo F

2018-04-28

Allium vegetables, such as garlic and onion, have understudied genomes and limited molecular resources, hindering advances in genetic research and breeding of these species. In this study, we characterized and compared the simple sequence repeats (SSR) landscape in the transcriptomes of garlic and related Allium (A. cepa, A. fistulosum, and A. tuberosum) and non-Allium monocot species. In addition, 110 SSR markers were developed from garlic ESTs, and they were characterized-along with 112 previously developed SSRs-at various levels, including transferability across Alliaceae species, and their usefulness for genetic diversity analysis. Among the Allium species analyzed, garlic ESTs had the highest overall SSR density, the lowest frequency of trinucleotides, and the highest of di- and tetranucleotides. When compared to more distantly related monocots, outside the Asparagales order, it was evident that ESTs of Allium species shared major commonalities with regards to SSR density, frequency distribution, sequence motifs, and GC content. A significant fraction of the SSR markers were successfully transferred across Allium species, including crops for which no SSR markers have been developed yet, such as leek, shallot, chives, and elephant garlic. Diversity analysis of garlic cultivars with selected SSRs revealed 36 alleles, with 2-5 alleles/locus, and PIC = 0.38. Cluster analysis grouped the accessions according to their flowering behavior, botanical variety, and ecophysiological characteristics. Results from this study contribute to the characterization of Allium transcriptomes. The new SSR markers developed, along with the data from the polymorphism and transferability analyses, will aid in assisting genetic research and breeding in garlic and other Allium.

Reduced bone mineral density in Japanese premenopausal women with systemic lupus erythematosus treated with glucocorticoids.

PubMed

Banno, S; Matsumoto, Y; Naniwa, T; Hayami, Y; Sugiura, Y; Yoshinouchi, T; Ueda, R

2002-12-01

Abstract We evaluated bone mineral density (BMD) in Japanese female patients with systemic lupus erythematosus (SLE) and assessed the influence of the use of glucocorticoids. Lumbar BMD was measured by dual x-ray absorptiometry (DXA) in 60 premenopausal females who previously had been receiving glucocorticoid therapy. Therapeutic- and disease-related variables for SLE were analyzed and bone resorption or formation markers were measured. Osteoporosis was defined as a T-score below 2.5 SD by DXA; 12 patients (20%) showed osteoporosis, and 30 (50%) had osteopenia. Compared with the nonosteoporotic group (n = 48), the osteoporotic group (n = 12) had a significantly longer duration of glucocorticoid treatment (P = 0.01), a cumulative prednisolone dose (P = 0.002), and an SLE damage index (SLICC/ACR). There was no difference in the incidence of osteoporosis either with or without the previous use of methyl-prednisolone pulse or immunosuppressive drugs. There was a significant positive correlation between urinary type I collagen cross-linked N-telopeptides (NTx) and serum bone-specific alkaline phosphatase (BAP) (r = 0.404, P = 0.002), but these bone metabolic markers showed no difference between the osteoporotic and nonosteoporotic groups. A good significant negative correlation was shown between BMD and the cumulative glucocorticoid dose (r = -0.351, P = 0.007). Stepwise logistic regression analysis showed that the cumulative glucocorticoid intake was independently associated with osteoporosis. Glucocorticoid-induced osteoporosis was frequently observed in Japanese SLE patients, as in Caucasian populations. The cumulative glucocorticoid dose was associated with an increased risk for osteoporosis. Bone metabolic markers such as NTx and BAP were not influenced by glucocorticoid treatment and could not predict current osteoporosis in SLE patients.

Cell Homogeneity Indispensable for Regenerative Medicine by Cultured Human Corneal Endothelial Cells.

PubMed

Hamuro, Junji; Toda, Munetoyo; Asada, Kazuko; Hiraga, Asako; Schlötzer-Schrehardt, Ursula; Montoya, Monty; Sotozono, Chie; Ueno, Morio; Kinoshita, Shigeru

2016-09-01

To identify the subpopulation (SP) among heterogeneous cultured human corneal endothelial cells (cHCECs) devoid of cell-state transition applicable for cell-based therapy. Subpopulation presence in cHCECs was confirmed via surface CD-marker expression level by flow cytometry. CD markers effective for distinguishing distinct SPs were selected by analyzing those on established cHCECs with a small cell area and high cell density. Contrasting features among three typical cHCEC SPs was confirmed by PCR array for extracellular matrix (ECM). Combined analysis of CD markers was performed to identify the SP (effector cells) applicable for therapy. ZO-1 and Na+/K+ ATPase, CD200, and HLA expression were compared among heterogeneous SPs. Flow cytometry analysis identified the effector cell expressing CD166+CD105-CD44-∼+/-CD26-CD24-, but CD200-, and the presence of other SPs with CD166+ CD105-CD44+++ (CD26 and CD24, either + or -) was confirmed. PCR array revealed three distinct ECM expression profiles. Some SPs expressed ZO-1 and Na+/K+ ATPase at comparable levels with effector cells, while only one SP expressed CD200, but not on effector cells. Human leukocyte antigen expression was most reduced in the effector SP. The proportion of effector cells (E-ratio) inversely paralleled donor age and decreased during prolonged culture passages. The presence of Rho-associated protein kinase (ROCK) inhibitor increased the E-ratio in cHCECs. The average area of effector cells was approximately 200∼220 μm2, and the density of cHCECs exceeded 2500 cells/mm2. A specified cultured effector cell population sharing the surface phenotypes with mature HCECs in corneal tissues may serve as an alternative to donor corneas for the treatment of corneal endothelial dysfunction.

Bone Mineral Density, Bone Turnover, and Systemic Inflammation in Non-cirrhotics with Chronic Hepatitis C.

PubMed

Lai, Jennifer C; Shoback, Dolores M; Zipperstein, Jacob; Lizaola, Blanca; Tseng, Samuel; Terrault, Norah A

2015-06-01

Whether chronic HCV, a disease characterized by systemic inflammation, impacts bone mineral density (BMD) independent of cirrhosis is unknown. We aimed to evaluate the association between BMD, systemic inflammation, and markers of bone turnover in chronic HCV without cirrhosis. Non-cirrhotics, 40-60 years old, with chronic HCV underwent measurement of: (1) BMD by dual-energy X-ray absorptiometry scan and (2) serum markers of systemic inflammation and bone turnover. By Chi-squared or t test, we compared those with normal versus low BMD. Of the 60 non-cirrhotics, 53 % were female and 53 % Caucasian. Mean (SD) age was 53.3 years (5.7), total bilirubin 0.7 mg/dL (0.3), creatinine 0.8 mg/dL (0.2), and body mass index 28.4 kg/m(2) (6.5). Low BMD was observed in 42 %: 30 % had osteopenia, 12 % had osteoporosis. Elevated tumor necrosis factor α, interleukin-6, and C-reactive protein levels were found in 26, 32, and 5 %, respectively, but did not differ by BMD group (p > 0.05). Patients with low BMD had higher serum phosphorus (4.1 vs. 3.5 mg/dL) and pro-peptide of type 1 collagen (P1NP; 73.1 vs. 47.5 ng/mL) [p < 0.05], but similar bone-specific alkaline phosphatase, serum C-telopeptide, and parathyroid hormone levels. Low BMD is prevalent in 40- to 60-year-old non-cirrhotics with chronic HCV, but not associated with systemic inflammatory markers. Elevated P1NP levels may help to identify those at increased risk of bone complications in this population. Chronic HCV should be considered a risk factor for bone loss, prompting earlier BMD assessments in both men and women.

Importance of Sox2 in maintenance of cell proliferation and multipotency of mesenchymal stem cells in low-density culture.

PubMed

Yoon, D S; Kim, Y H; Jung, H S; Paik, S; Lee, J W

2011-10-01

This study has aimed to repopulate 'primitive' cells from late-passage mesenchymal stem cells (MSCs) of poor multipotentiality and low cell proliferation rate, by simply altering plating density. Effects of low density culture compared t high density culture on late-passage bone marrow (BM)-derived MSCs and pluripotency markers of multipotentiality were investigated. Cell proliferation, gene expression, RNA interference and differentiation potential were assayed. We repopulated 'primitive' cells by replating late-passage MSCs at low density (17 cells/cm(2) ) regardless of donor age. Repopulated MSCs from low-density culture were smaller cells with spindle shaped morphology compared to MSCs from high-density culture. The latter had enhanced colony-forming ability, proliferation rate, and adipogenic and chondrogenic potential. Strong expression of osteogenic-related genes (Cbfa1, Dlx5, alkaline phosphatase and type Ι collagen) in late-passage MSCs was reduced by replating at low density, whereas expression of three pluripotency markers (Sox2, Nanog and Oct-4), Osterix and Msx2 reverted to levels of early-passage MSCs. Knockdown of Sox2 and Msx2 but not Nanog, using RNA interference, showed significant decrease in colony-forming ability. Specifically, knockdown of Sox2 significantly inhibited multipotentiality and cell proliferation. Our data suggest that plating density should be considered to be a critical factor for enrichment of 'primitive' cells from heterogeneous BM and that replicative senescence and multipotentiality of MSCs during in vitro expansion may be predominantly regulated through Sox2. © 2011 Blackwell Publishing Ltd.

Relevance of the triglyceride-to-high-density lipoprotein cholesterol ratio as an important lipid fraction in apparently healthy, young, and middle-aged Indian men

PubMed Central

Kohli, Aparna; Siddhu, Anupa; Pandey, Ravindra M.; Reddy, K. Srinath

2017-01-01

Context: Cardiovascular disease (CVD) is the largest cause of mortality in Indians. Insulin resistance and related dyslipidemia of increased triglyceride (TG), small dense low-density lipoprotein (sd-LDL) particles, and decreased high-density lipoprotein-cholesterol (HDL-C) are associated with increased risk of CVD. TG/HDL-C ratio could be a potential surrogate marker for this South Asian phenotype. Data are scarce on the relevance of TG/HDL-C ratio as a useful lipid marker among Indians. Aims: To study the prevalence of TG/HDL-C ratio among healthy, young, and middle-aged Indian men (25–44 years) and its relationship with other lipid and nonlipid factors. Subjects and Methods: In this cross-sectional analysis, fasting blood samples from 236 healthy participants recruited from an urban community setting were tested for TG/HDL-C ratio, HDL-C, TG, total cholesterol (TC), non-HDL-C, TC/HDL-C, high-sensitivity C-reactive protein, body mass index (BMI), and body fat. Results: Mean (standard deviation) age of participants was 34.7 (7.7) years; median (interquartile range) TG/HDL-C ratio was 4 (2.85-5.2). More than half (51.3%) the participants (n = 121) recorded abnormal TG/HDL-C ratio (≥4.0). Across tertiles of TG/HDL-C ratio, there was a significant trend of higher conventional lipid parameters such as non-HDL-C*, TC/HDL-C ratio*, TG*, HDL-C*, TC**; and non-lipid parameters body-fat* and BMI*** (*P < 0.001, **P = 0.015, ***P = 0.002). LDL-C showed moderate and nonsignificant (P = 0.646) increase across tertiles. Conclusion: In a sample of apparently healthy, young, and middle-aged Indian men abnormal TG/HDL-C ratio levels were observed among more than half the participants. The TG/HDL-C ratio was closely associated with other lipid parameters and measures of adiposity, such as BMI and body fat, apart from its previously documented unique association with sd-LDL particles. TG/HDL-C ratio should be evaluated in future for risk prediction of incident CVD among Indians. PMID:28217509

Relevance of the triglyceride-to-high-density lipoprotein cholesterol ratio as an important lipid fraction in apparently healthy, young, and middle-aged Indian men.

PubMed

Kohli, Aparna; Siddhu, Anupa; Pandey, Ravindra M; Reddy, K Srinath

2017-01-01

Cardiovascular disease (CVD) is the largest cause of mortality in Indians. Insulin resistance and related dyslipidemia of increased triglyceride (TG), small dense low-density lipoprotein (sd-LDL) particles, and decreased high-density lipoprotein-cholesterol (HDL-C) are associated with increased risk of CVD. TG/HDL-C ratio could be a potential surrogate marker for this South Asian phenotype. Data are scarce on the relevance of TG/HDL-C ratio as a useful lipid marker among Indians. To study the prevalence of TG/HDL-C ratio among healthy, young, and middle-aged Indian men (25-44 years) and its relationship with other lipid and nonlipid factors. In this cross-sectional analysis, fasting blood samples from 236 healthy participants recruited from an urban community setting were tested for TG/HDL-C ratio, HDL-C, TG, total cholesterol (TC), non-HDL-C, TC/HDL-C, high-sensitivity C-reactive protein, body mass index (BMI), and body fat. Mean (standard deviation) age of participants was 34.7 (7.7) years; median (interquartile range) TG/HDL-C ratio was 4 (2.85-5.2). More than half (51.3%) the participants ( n = 121) recorded abnormal TG/HDL-C ratio (≥4.0). Across tertiles of TG/HDL-C ratio, there was a significant trend of higher conventional lipid parameters such as non-HDL-C*, TC/HDL-C ratio*, TG*, HDL-C*, TC**; and non-lipid parameters body-fat* and BMI*** (* P < 0.001, ** P = 0.015, *** P = 0.002). LDL-C showed moderate and nonsignificant ( P = 0.646) increase across tertiles. In a sample of apparently healthy, young, and middle-aged Indian men abnormal TG/HDL-C ratio levels were observed among more than half the participants. The TG/HDL-C ratio was closely associated with other lipid parameters and measures of adiposity, such as BMI and body fat, apart from its previously documented unique association with sd-LDL particles. TG/HDL-C ratio should be evaluated in future for risk prediction of incident CVD among Indians.

Third generation anthropomorphic physical phantom for mammography and DBT: incorporating voxelized 3D printing and uniform chest wall QC region

NASA Astrophysics Data System (ADS)

Zhao, Christine; Solomon, Justin; Sturgeon, Gregory M.; Gehm, Michael E.; Catenacci, Matthew; Wiley, Benjamin J.; Samei, Ehsan; Lo, Joseph Y.

2017-03-01

Physical breast phantoms provide a standard method to test, optimize, and develop clinical mammography systems, including new digital breast tomosynthesis (DBT) systems. In previous work, we produced an anthropomorphic phantom based on 500x500x500 μm breast CT data using commercial 3D printing. We now introduce an improved phantom based on a new cohort of virtual models with 155x155x155 μm voxels and fabricated through voxelized 3D printing and dithering, which confer higher resolution and greater control over contrast. This new generation includes a uniform chest wall extension for evaluating conventional QC metrics. The uniform region contains a grayscale step wedge, chest wall coverage markers, fiducial markers, spheres, and metal ink stickers of line pairs and edges to assess contrast, resolution, artifact spread function, MTF, and other criteria. We also experimented with doping photopolymer material with calcium, iodine, and zinc to increase our current contrast. In particular, zinc was discovered to significantly increase attenuation beyond 100% breast density with a linear relationship between zinc concentration and attenuation or breast density. This linear relationship was retained when the zinc-doped material was applied in conjunction with 3D printing. As we move towards our long term goal of phantoms that are indistinguishable from patients, this new generation of anthropomorphic physical breast phantom validates our voxelized printing process, demonstrates the utility of a uniform QC region with features from 3D printing and metal ink stickers, and shows potential for improved contrast via doping.

Longitudinal study of bone loss in pre- and perimenopausal women: evidence for bone loss in perimenopausal women.

PubMed

Chapurlat, R D; Garnero, P; Sornay-Rendu, E; Arlot, M E; Claustrat, B; Delmas, P D

2000-01-01

Bone loss before and around the time of menopause is not well characterized by longitudinal studies. We measured bone mineral density at various skeletal sites--total body, femoral neck, trochanter, anteroposterior (AP) and lateral spine, and forearm--with dual-energy X-ray absorptiometry in a large prospective cohort of 272 untreated pre- and perimenopausal women aged 31-59 years, at 1 year intervals for 3 years. Sex steroids and the following markers of bone remodeling were measured: serum osteocalcin (OC), procollagen I carboxyterminal extension peptide, bone alkaline phosphatase (BAP) and urinary crosslinks (CTX and NTX). Seventy-six women were classified as perimenopausal and 196 as premenopausal. Over the 3 years, premenopausal women had no significant bone loss at any site and a small but significant increase in bone mineral density at the trochanter, total hip, AP spine and radius. Perimenopausal women significantly lost bone from cancellous and cortical sites, i.e., the femoral neck, trochanter and lumbar spine. In perimenopausal women with increased follicle stimulating hormone, the rate of bone loss at the femoral neck correlated negatively with OC and BAP. In perimenopausal women, serum estradiol levels decreased during the 3 years of follow-up and bone loss from the trochanter and the AP spine was correlated with serum estradiol after 3 years. In conclusion, among premenopausal women there is no bone loss. In contrast, there is a rapid and diffuse bone loss in perimenopausal women, related to decreased estrogen secretion. Bone markers may be useful to identify these women losing bone.

Effect of Probiotic Lactobacillus salivarius UBL S22 and Prebiotic Fructo-oligosaccharide on Serum Lipids, Inflammatory Markers, Insulin Sensitivity, and Gut Bacteria in Healthy Young Volunteers: A Randomized Controlled Single-Blind Pilot Study.

PubMed

Rajkumar, Hemalatha; Kumar, Manoj; Das, Nilita; Kumar, S Nishanth; Challa, Hanumanth R; Nagpal, Ravinder

2015-05-01

This study investigated the effect of 6-week supplementation of a probiotic strain Lactobacillus salivarius UBL S22 with or without prebiotic fructo-oligosaccharide (FOS) on serum lipid profiles, immune responses, insulin sensitivity, and gut lactobacilli in 45 healthy young individuals. The patients were divided into 3 groups (15/group), that is, placebo, probiotic, and synbiotic. After 6 weeks, a significant reduction (P < .05) in total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides and increase in high-density lipoprotein cholesterol was observed in the probiotic as well as in the synbiotic group when compared to placebo; however, the results of total cholesterol and LDL-cholesterol were more pronounced in the synbiotic group. Similarly, when compared to the placebo group, the serum concentrations of inflammatory markers such as high sensitivity C-reactive protein, interleukin (IL) 6, IL-1β, and tumor necrosis factor α were significantly (P < .05) reduced in both the experimental groups, but again the reduction in the synbiotic group was more pronounced. Also, an increase (P < .05) in the fecal counts of total lactobacilli and a decrease (P < .05) in coliforms and Escherichia coli was observed in both the experimental groups after 6 weeks of ingestion. Overall, the combination of L salivarius with FOS was observed to be more beneficial than L salivarius alone, thereby advocating that such synbiotic combinations could be therapeutically exploited for improved health and quality of life. © The Author(s) 2014.

Genome-wide scan for genes involved in bipolar affective disorder in 70 European families ascertained through a bipolar type I early-onset proband: supportive evidence for linkage at 3p14

PubMed Central

Etain, Bruno; Mathieu, Flavie; Rietschel, Marcella; Maier, Wolfgang; Albus, Margot; Mckeon, Patrick; Roche, S.; Kealey, Carmel; Blackwood, Douglas; Muir, Walter; Bellivier, Franc; Henry, C.; Dina, Christian; Gallina, Sophie; Gurling, H.; Malafosse, Alain; Preisig, Martin; Ferrero, François; Cichon, Sven; Schumacher, J.; Ohlraun, Stéphanie; Borrmann-Hassenbach, M.; Propping, Peter; Abou Jamra, Rami; Schulze, Thomas G.; Marusic, Andrej; Dernovsek, Mojca Z.; Giros, Bruno; Bourgeron, Thomas; Lemainque, Arnaud; Bacq, Delphine; Betard, Christine; Charon, Céline; Nöthen, Markus M.; Lathrop, Mark; Leboyer, Marion

2006-01-01

Summary Preliminary studies suggested that age at onset (AAO) may help to define homogeneous bipolar affective disorder (BPAD) subtypes. This candidate symptom approach might be useful to identify vulnerability genes. Thus, the probability of detecting major disease-causing genes might be increased by focusing on families with early-onset BPAD type I probands. This study was conducted as part of the European Collaborative Study of Early Onset BPAD (France, Germany, Ireland, Scotland, Switzerland, England, Slovenia). We performed a genome-wide search with 384 microsatellite markers using non parametric linkage analysis in 87 sib-pairs ascertained through an early-onset BPAD type I proband (age at onset of 21 years or below). Non parametric multi-point analysis suggested eight regions of linkage with p-values <0.01 (2p21, 2q14.3, 3p14, 5q33, 7q36, 10q23, 16q23 and 20p12). The 3p14 region showed the most significant linkage (genome-wide p-value estimated over 10.000 simulated replicates of 0.015 [0.01–0.02]). After genome-wide search analysis, we performed additional linkage analyses with increase marker density using markers in four regions suggestive for linkage and having an information contents lower than 75% (3p14, 10q23, 16q23 and 20p12). For these regions, the information content improved by about 10%. In chromosome 3, the non parametric linkage score increased from 3.51 to 3.83. This study is the first to use early onset bipolar type I probands in an attempt to increase sample homogeneity. These preliminary findings require confirmation in independent panels of families. PMID:16534504

Artificial Gravity: Effects on Bone Turnover

NASA Technical Reports Server (NTRS)

Heer, M.; Zwart, S /R.; Baecker, N.; Smith, S. M.

2007-01-01

The impact of microgravity on the human body is a significant concern for space travelers. Since mechanical loading is a main reason for bone loss, artificial gravity might be an effective countermeasure to the effects of microgravity. In a 21-day 6 head-down tilt bed rest (HDBR) pilot study carried out by NASA, USA, the utility of artificial gravity (AG) as a countermeasure to immobilization-induced bone loss was tested. Blood and urine were collected before, during, and after bed rest for bone marker determinations. Bone mineral density was determined by DXA and pQCT before and after bed rest. Urinary excretion of bone resorption markers (n-telopeptide and helical peptide) were increased from pre-bed rest, but there was no difference between the control and the AG group. The same was true for serum c-telopeptide measurements. Bone formation markers were affected by bed rest and artificial gravity. While bone-specific alkaline phosphatase tended to be lower in the AG group during bed rest (p = 0.08), PINP, another bone formation marker, was significantly lower in AG subjects than CN before and during bed rest. PINP was lower during bed rest in both groups. For comparison, artificial gravity combined with ergometric exercise was tested in a 14-day HDBR study carried out in Japan (Iwase et al. J Grav Physiol 2004). In that study, an exercise regime combined with AG was able to significantly mitigate the bed rest-induced increase in the bone resorption marker deoxypyridinoline. While further study is required to more clearly differentiate bone and muscle effects, these initial data demonstrate the potential effectiveness of short-radius, intermittent AG as a countermeasure to the bone deconditioning that occurs during bed rest and spaceflight. Future studies will need to optimize not only the AG prescription (intensity and duration), but will likely need to include the use of exercise or other combined treatments.

Impact of mild versus moderate intensity aerobic walking exercise training on markers of bone metabolism and hand grip strength in moderate hemophilic A patients.

PubMed

Al-Sharif, Fadwa Al-Ghalib; Al-Jiffri, Osama Hussien; El-Kader, Shehab Mahmoud Abd; Ashmawy, Eman Mohamed

2014-03-01

Patients with hemophilia A have low bone density than healthy controls. It is now widely recognized that physical activity and sports are beneficial for patients with hemophilia. To compare the effects of mild and moderate intensity treadmill walking exercises on markers of bone metabolism and hand grip strength in male patients with moderate hemophilia A. Fifty male patients with moderate hemophilia, and age range from 25 to 45 years. The subjects were randomly assigned into 2 equal groups; the first group (A) received moderate intensity aerobic exercise training. The second group (B) received mild intensity aerobic exercise training. There was a 32.1% and 24.8% increase in mean values of serum calcium and hand grip strength respectively and 22.7 % reduction in mean values of parathyroid hormone in moderate exercise training group (A). While there was a 15.1 % and 15 % increase in mean values of Serum Calcium and Hand grip strength respectively and 10.3 % reduction in mean values of parathyroid hormone in mild exercise training group(B). The mean values of serum calcium and hand grip strength were significantly increased, while the mean values of parathyroid hormone were significantly decreased in both groups . There were significant differences between mean levels of the investigated parameters in group (A) and group (B) after treatment. Moderate intensity aerobic exercise training on treadmill is appropriate to improve markers of bone metabolism and hand grip strength in male patients with hemophilia A.

Evidence for chronic low-grade systemic inflammation in individuals with agoraphobia from a population-based prospective study.

PubMed

Wagner, En-Young N; Wagner, Jan T; Glaus, Jennifer; Vandeleur, Caroline L; Castelao, Enrique; Strippoli, Marie-Pierre F; Vollenweider, Peter; Preisig, Martin; von Känel, Roland

2015-01-01

Anxiety disorders have been linked to an increased risk of incident coronary heart disease in which inflammation plays a key pathogenic role. To date, no studies have looked at the association between proinflammatory markers and agoraphobia. In a random Swiss population sample of 2890 persons (35-67 years, 53% women), we diagnosed a total of 124 individuals (4.3%) with agoraphobia using a validated semi-structured psychiatric interview. We also assessed socioeconomic status, traditional cardiovascular risk factors (i.e., body mass index, hypertension, blood glucose levels, total cholesterol/high-density lipoprotein-cholesterol ratio), and health behaviors (i.e., smoking, alcohol consumption, and physical activity), and other major psychiatric diseases (other anxiety disorders, major depressive disorder, drug dependence) which were treated as covariates in linear regression models. Circulating levels of inflammatory markers, statistically controlled for the baseline demographic and health-related measures, were determined at a mean follow-up of 5.5 ± 0.4 years (range 4.7 - 8.5). Individuals with agoraphobia had significantly higher follow-up levels of C-reactive protein (p = 0.007) and tumor-necrosis-factor-α (p = 0.042) as well as lower levels of the cardioprotective marker adiponectin (p = 0.032) than their non-agoraphobic counterparts. Follow-up levels of interleukin (IL)-1β and IL-6 did not significantly differ between the two groups. Our results suggest an increase in chronic low-grade inflammation in agoraphobia over time. Such a mechanism might link agoraphobia with an increased risk of atherosclerosis and coronary heart disease, and needs to be tested in longitudinal studies.

The effect of levetiracetam on rat bone mass, structure and metabolism.

PubMed

Fekete, Sona; Simko, Julius; Gradosova, Iveta; Malakova, Jana; Zivna, Helena; Palicka, Vladimir; Zivny, Pavel

2013-11-01

To determine the effect of levetiracetam (LEV) Lon bone mineral density (BMD), mineral content (BMC), bone markers, body composition and bone mechanical strength in the orchidectomised (ORX) rat model. 16 orchidectomised Wistar rats were divided into control and test groups, 8 rats in each group. The control rats received standard laboratory diet (SLD) while rats in the test group were fed with SLD enriched with LEV for 12 weeks. BMD was measured by dual energy X-ray absorptiometry at the whole body, lumbar spine and femur. Bone marker concentrations were examined of osteoprotegerin (OPG) and insulin-like growth factor 1 (IGF-1) in serum, and amino-terminal propeptide of procollagen type I (PINP), carboxy-terminal cross-linking telopeptide of type I collagen (CTX-I), bone alkaline phosphatase (ALPL), and bone morphogenetic protein 2 (BMP-2) in bone homogenate. The femurs were used for biomechanical testing. Compared to the control group we found lower fat mass, lower BMD in the area of the left femur, lower BMC in both femurs, a reduced concentration of OPG, and an increased concentration of CTX-I of borderline statistical significance (p=0.0661). Biomechanical parameters did not differ between groups. Significant loss of BMD or BMC was seen at the left and right femur area in the LEV group. Administration of LEV in the ORX-rat model significantly decreased levels of OPG (marker of bone formation) in serum and increased levels of CTX-I (marker of bone resorption) in bone homogenate, but results in this study did not reveal any change in biomechanical bone strength. Administration of LEV in the ORX-rat model may reduce adipose tissue. Further studies in animals and humans will be needed to confirm these findings. Copyright © 2013 Elsevier B.V. All rights reserved.

Acute ketamine administration corrects abnormal inflammatory bone markers in major depressive disorder.

PubMed

Kadriu, B; Gold, P W; Luckenbaugh, D A; Lener, M S; Ballard, E D; Niciu, M J; Henter, I D; Park, L T; De Sousa, R T; Yuan, P; Machado-Vieira, R; Zarate, C A

2017-05-30

Patients with major depressive disorder (MDD) have clinically relevant, significant decreases in bone mineral density (BMD). We sought to determine if predictive markers of bone inflammation-the osteoprotegerin (OPG)-RANK-RANKL system or osteopontin (OPN)-play a role in the bone abnormalities associated with MDD and, if so, whether ketamine treatment corrected the abnormalities. The OPG-RANK-RANKL system plays the principal role in determining the balance between bone resorption and bone formation. RANKL is the osteoclast differentiating factor and diminishes BMD. OPG is a decoy receptor for RANKL, thereby increasing BMD. OPN is the bone glue that acts as a scaffold between bone tissues matrix composition to bind them together and is an important component of bone strength and fracture resistance. Twenty-eight medication-free inpatients with treatment-resistant MDD and 16 healthy controls (HCs) participated in the study. Peripheral bone marker levels and their responses to IV ketamine infusion in MDD patients and HCs were measured at four time points: at baseline, and post-infusion at 230 min, Day 1, and Day 3. Patients with MDD had significant decreases in baseline OPG/RANKL ratio and in plasma OPN levels. Ketamine significantly increased both the OPG/RANKL ratio and plasma OPN levels, and significantly decreased RANKL levels. Bone marker levels in HCs remained unaltered. We conclude that the OPG-RANK-RANKL system and the OPN system play important roles in the serious bone abnormalities associated with MDD. These data suggest that, in addition to its antidepressant effects, ketamine also has a salutary effect on a major medical complication of depressive illness.Molecular Psychiatry advance online publication, 30 May 2017; doi:10.1038/mp.2017.109.

A high-density genetic map of Arachis duranensis, a diploid ancestor of cultivated peanut

PubMed Central

2012-01-01

Background Cultivated peanut (Arachis hypogaea) is an allotetraploid species whose ancestral genomes are most likely derived from the A-genome species, A. duranensis, and the B-genome species, A. ipaensis. The very recent (several millennia) evolutionary origin of A. hypogaea has imposed a bottleneck for allelic and phenotypic diversity within the cultigen. However, wild diploid relatives are a rich source of alleles that could be used for crop improvement and their simpler genomes can be more easily analyzed while providing insight into the structure of the allotetraploid peanut genome. The objective of this research was to establish a high-density genetic map of the diploid species A. duranensis based on de novo generated EST databases. Arachis duranensis was chosen for mapping because it is the A-genome progenitor of cultivated peanut and also in order to circumvent the confounding effects of gene duplication associated with allopolyploidy in A. hypogaea. Results More than one million expressed sequence tag (EST) sequences generated from normalized cDNA libraries of A. duranensis were assembled into 81,116 unique transcripts. Mining this dataset, 1236 EST-SNP markers were developed between two A. duranensis accessions, PI 475887 and Grif 15036. An additional 300 SNP markers also were developed from genomic sequences representing conserved legume orthologs. Of the 1536 SNP markers, 1054 were placed on a genetic map. In addition, 598 EST-SSR markers identified in A. hypogaea assemblies were included in the map along with 37 disease resistance gene candidate (RGC) and 35 other previously published markers. In total, 1724 markers spanning 1081.3 cM over 10 linkage groups were mapped. Gene sequences that provided mapped markers were annotated using similarity searches in three different databases, and gene ontology descriptions were determined using the Medicago Gene Atlas and TAIR databases. Synteny analysis between A. duranensis, Medicago and Glycine revealed significant stretches of conserved gene clusters spread across the peanut genome. A higher level of colinearity was detected between A. duranensis and Glycine than with Medicago. Conclusions The first high-density, gene-based linkage map for A. duranensis was generated that can serve as a reference map for both wild and cultivated Arachis species. The markers developed here are valuable resources for the peanut, and more broadly, to the legume research community. The A-genome map will have utility for fine mapping in other peanut species and has already had application for mapping a nematode resistance gene that was introgressed into A. hypogaea from A. cardenasii. PMID:22967170

Preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats.

PubMed

Roy, Abhro Jyoti; Stanely Mainzen Prince, P

2013-10-01

The present study evaluated the preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats. Rats were pretreated with p-coumaric acid (8 mg/kg body weight) daily for a period of 7 days and then injected with isoproterenol (100mg/kg body weight) on 8th and 9th day to induce myocardial infarction. Myocardial infarction induced by isoproterenol was indicated by increased level of cardiac sensitive marker and elevated ST-segments in the electrocardiogram. Also, the levels/concentrations of serum and heart cholesterol, triglycerides and free fatty acids were increased in myocardial infarcted rats. Isoproterenol also increased the levels of serum low density and very low density lipoprotein cholesterol and decreased the levels of high density lipoprotein cholesterol. It also enhanced the activity of liver 3-hydroxy-3 methyl glutaryl-Coenzyme-A reductase. p-Coumaric acid pretreatment revealed preventive effects on all the biochemical parameters and electrocardiogram studied in myocardial infarcted rats. The in vitro study confirmed the free radical scavenging property of p-coumaric acid. Thus, p-coumaric acid prevented cardiac hypertrophy and alterations in lipids, lipoproteins, and electrocardiogram, by virtue of its antihypertrophic, antilipidemic, and free radical scavenging effects in isoproterenol induced myocardial infarcted rats. Copyright © 2013 Elsevier Ltd. All rights reserved.

Association of Glycemic Status with Bone Turnover Markers in Type 2 Diabetes Mellitus.

PubMed

Kulkarni, Sweta Vilas; Meenatchi, Suruthi; Reeta, R; Ramesh, Ramasamy; Srinivasan, A R; Lenin, C

2017-01-01

Type 2 diabetes mellitus has profound implications on the skeleton. Even though bone mineral density is increased in type 2 diabetes mellitus patients, they are more prone for fractures. The weakening of bone tissue in type 2 diabetes mellitus can be due to uncontrolled blood sugar levels leading to high levels of bone turnover markers in blood. The aim of this study is to find the association between glycemic status and bone turnover markers in type 2 diabetes mellitus. This case-control study was carried out in a tertiary health care hospital. Fifty clinically diagnosed type 2 diabetes mellitus patients in the age group between 30 and 50 years were included as cases. Fifty age- and gender-matched healthy nondiabetics were included as controls. Patients with complications and chronic illness were excluded from the study. Depending on glycated hemoglobin (HbA1c) levels, patients were grouped into uncontrolled (HbA1c >7%, n = 36) and controlled (HbA1c <7%, n = 14) diabetics. Based on duration of diabetes, patients were grouped into newly diagnosed, 1-2 years, 3-5 years, and >5 years. Serum osteocalcin (OC), bone alkaline phosphatase (BAP), acid phosphatase (ACP), and HbA1c levels were estimated. OC/BAP and OC/ACP ratio was calculated. Student's t -test, analysis of variance, and Chi-square tests were used for analysis. Receiver operating characteristic (ROC) curve analysis was done for OC/BAP and OC/ACP ratios. Serum OC, HbA1c, and OC/BAP ratio were increased in cases when compared to controls and were statistically significant ( P < 0.001). OC/ACP ratio was decreased in type 2 diabetes mellitus and was statistically significant ( P = 0.01). In patients with >5-year duration of diabetes, HbA1c level was high and was statistically significant ( P < 0.042). BAP levels were high in uncontrolled diabetics but statistically not significant. ROC curve showed OC/BAP ratio better marker than OC/ACP ratio. Uncontrolled type 2 diabetes mellitus affects bone tissue resulting in variations in bone turnover markers. Bone turnover markers are better in predicting recent changes in bone morphology and are cost effective.

Retrospective Study of Serum Sclerostin Measurements in Bed Rest Subjects

NASA Technical Reports Server (NTRS)

Spatz, J. M.; Fields, E. E.; Yu, E. W.; Divieti, Pajevic P.; Bouxsein, M. L.; Sibonga, M. L.; Zwart, S. R.; Smith, S. M.

2011-01-01

Animal models and human studies suggest that osteocytes regulate the skeleton s response to mechanical unloading at the cellular level in part by an increase in sclerostin, an inhibitor of the anabolic Wnt pathway. However, few studies have reported changes in serum sclerostin in humans exposed to reduced mechanical loading. Thus, we determined changes in serum sclerostin and bone turnover markers in healthy adult men who participated in a controlled bed rest study. Seven healthy adult men (31 +/- 3 yrs old) underwent 90-day six-degree head down tilt bed rest at the University of Texas Medical Branch in Galveston's Institute for Translational Sciences - Clinical Research Center (ITS-CRC). Serum sclerostin, PTH, serum markers of bone turnover (bone specific alkaline phosphatase, RANKL/OPG, and osteocalcin), urinary calcium and phosphorus excretion, and 24 hour pooled urinary markers of bone resorption (NTX, DPD, PYD) were evaluated pre-bed rest (BL), bed rest day 28 (BR-28), bed rest day 60 (BR-60), and bed rest day 90 (BR-90). In addition, bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry (DXA) at BL, BR-60, and post bed rest day 5 (BR+5). Data are reported as mean +/- standard deviation. We used repeated measures ANOVA to compare baseline values to BR-28, BR-60, and BR-90. RESULTS Consistent with prior reports, BMD declined significantly (1-2% per month) at weight-bearing skeletal sites (spine, hip, femur neck, and calcaneus). Serum sclerostin levels were elevated above BL at BR-28 (+29% +/- 20%, p = 0.003), BR-60 (+42% +/- 31%, p < 0.001), and BR-90 (22% +/- 21%, p = 0.07). Serum PTH levels were reduced at BR-28 (-17% +/- 16%, p = 0.02), BR-60 (-24% +/- 14%, p = 0.03), and returned to baseline at BR-90 (-21% +/- 21%, p = 0.14). Serum bone turnover markers did not change, however urinary bone resorption markers and calcium were significantly elevated following bed rest (p < 0.01). CONCLUSION We observed an increase of serum sclerostin associated with decreased serum PTH and elevated bone resorption markers in otherwise healthy men subjected to long-term immobilization.

Effect of high dietary sodium on bone turnover markers and urinary calcium excretion in Korean postmenopausal women with low bone mass.

PubMed

Park, S M; Joung, J Y; Cho, Y Y; Sohn, S Y; Hur, K Y; Kim, J H; Kim, S W; Chung, J H; Lee, M K; Min, Y-K

2015-03-01

High salt intake is a well-recognized risk factor of osteoporosis for its modulating effect on calcium metabolism. To understand the effect of dietary sodium on bone turnover, we evaluated the association between urinary sodium excretion and bone turnover markers in Korean postmenopausal women with low bone mass. A retrospective review of medical records at a single institution identified 537 postmenopausal women who were first diagnosed with osteopenia or osteoporosis between 2008 and 2013. Subjects were stratified by low (<2 g/day, n=77), moderate (2-4.4 g/day, n=354) and high (⩾4.4 g/day, n=106) sodium excretion. A 24-h urine was collected to estimate sodium, calcium and creatinine. Bone turnover markers and calciotropic hormones were measured in serum. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry. Sodium intake was positively associated with urinary sodium excretion (P=0.006, r=0.29). Bone turnover markers were significantly higher in the moderate-to-high urinary sodium excretion group (⩾2 g/day) than in the low urinary sodium excretion group (<2 g/day); CTX-I (C-telopeptides of type I collagen) was 21.3% higher (P=0.001) and osteocalcin (OC) was 15.7% higher (P=0.004). Calciotropic hormones and BMD were not significantly different across the sodium excretion groups. High urinary sodium excretion (⩾2 g/day) increased bone turnover markers in Korean postmenopausal women, suggesting that excessive sodium intake might accelerate bone turnover.

Environmental DNA Marker Development with Sparse Biological Information: A Case Study on Opossum Shrimp (Mysis diluviana).

PubMed

Carim, Kellie J; Christianson, Kyle R; McKelvey, Kevin M; Pate, William M; Silver, Douglas B; Johnson, Brett M; Galloway, Benjamin T; Young, Michael K; Schwartz, Michael K

2016-01-01

The spread of Mysis diluviana, a small glacial relict crustacean, outside its native range has led to unintended shifts in the composition of native fish communities throughout western North America. As a result, biologists seek accurate methods of determining the presence of M. diluviana, especially at low densities or during the initial stages of an invasion. Environmental DNA (eDNA) provides one solution for detecting M. diluviana, but building eDNA markers that are both sensitive and species-specific is challenging when the distribution and taxonomy of closely related non-target taxa are poorly understood, published genetic data are sparse, and tissue samples are difficult to obtain. To address these issues, we developed a pair of independent eDNA markers to increase the likelihood of a positive detection of M. diluviana when present and reduce the probability of false positive detections from closely related non-target species. Because tissue samples of closely-related and possibly sympatric, non-target taxa could not be obtained, we used synthetic DNA sequences of closely related non-target species to test the specificity of eDNA markers. Both eDNA markers yielded positive detections from five waterbodies where M. diluviana was known to be present, and no detections in five others where this species was thought to be absent. Daytime samples from varying depths in one waterbody occupied by M. diluviana demonstrated that samples near the lake bottom produced 5 to more than 300 times as many eDNA copies as samples taken at other depths, but all samples tested positive regardless of depth.

Irradiation-Dependent Effects on Tumor Perfusion and Endogenous and Exogenous Hypoxia Markers in an A549 Xenograft Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fokas, Emmanouil, E-mail: emmanouil.fokas@yahoo.d; Haenze, Joerg; Kamlah, Florentine

2010-08-01

Purpose: Hypoxia is a major determinant of tumor radiosensitivity, and microenvironmental changes in response to ionizing radiation (IR) are often heterogenous. We analyzed IR-dependent changes in hypoxia and perfusion in A549 human lung adenocarcinoma xenografts. Materials and Methods: Immunohistological analysis of two exogenously added chemical hypoxic markers, pimonidazole and CCI-103F, and of the endogenous marker Glut-1 was performed time dependently after IR. Tumor vessels and apoptosis were analyzed using CD31 and caspase-3 antibodies. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and fluorescent beads (Hoechst 33342) were used to monitor vascular perfusion. Results: CCI-103F signals measuring the fraction of hypoxic areas aftermore » IR were significantly decreased by approximately 50% when compared with pimonidazole signals, representing the fraction of hypoxic areas from the same tumors before IR. Interestingly, Glut-1 signals were significantly decreased at early time point (6.5 h) after IR returning to the initial levels at 30.5 h. Vascular density showed no difference between irradiated and control groups, whereas apoptosis was significantly induced at 10.5 h post-IR. DCE-MRI indicated increased perfusion 1 h post-IR. Conclusions: The discrepancy between the hypoxic fractions of CCI-103F and Glut-1 forces us to consider the possibility that both markers reflect different metabolic alterations of tumor microenvironment. The reliability of endogenous markers such as Glut-1 to measure reoxygenation in irradiated tumors needs further consideration. Monitoring tumor microvascular response to IR by DCE-MRI and measuring tumor volume alterations should be encouraged.« less

Genome-wide association study (GWAS) for growth rate and age at sexual maturation in Atlantic salmon (Salmo salar).

PubMed

Gutierrez, Alejandro P; Yáñez, José M; Fukui, Steve; Swift, Bruce; Davidson, William S

2015-01-01

Early sexual maturation is considered a serious drawback for Atlantic salmon aquaculture as it retards growth, increases production times and affects flesh quality. Although both growth and sexual maturation are thought to be complex processes controlled by several genetic and environmental factors, selection for these traits has been continuously accomplished since the beginning of Atlantic salmon selective breeding programs. In this genome-wide association study (GWAS) we used a 6.5K single-nucleotide polymorphism (SNP) array to genotype ∼ 480 individuals from the Cermaq Canada broodstock program and search for SNPs associated with growth and age at sexual maturation. Using a mixed model approach we identified markers showing a significant association with growth, grilsing (early sexual maturation) and late sexual maturation. The most significant associations were found for grilsing, with markers located in Ssa10, Ssa02, Ssa13, Ssa25 and Ssa12, and for late maturation with markers located in Ssa28, Ssa01 and Ssa21. A lower level of association was detected with growth on Ssa13. Candidate genes, which were linked to these genetic markers, were identified and some of them show a direct relationship with developmental processes, especially for those in association with sexual maturation. However, the relatively low power to detect genetic markers associated with growth (days to 5 kg) in this GWAS indicates the need to use a higher density SNP array in order to overcome the low levels of linkage disequilibrium observed in Atlantic salmon before the information can be incorporated into a selective breeding program.

Does methamphetamine affect bone metabolism?

PubMed

Tomita, Masafumi; Katsuyama, Hironobu; Watanabe, Yoko; Okuyama, Toshiko; Fushimi, Shigeko; Ishikawa, Takaki; Nata, Masayuki; Miyamoto, Osamu

2014-05-07

There is a close relationship between the central nervous system activity and bone metabolism. Therefore, methamphetamine (METH), which stimulates the central nervous system, is expected to affect bone turnover. The aim of this study was to investigate the role of METH in bone metabolism. Mice were divided into 3 groups, the control group receiving saline injections, and the 5 and 10mg/kg METH groups (n=6 in each group). All groups received an injection of saline or METH every other day for 8 weeks. Bone mineral density (BMD) was assessed by X-ray computed tomography. We examined biochemical markers and histomorphometric changes in the second cancellous bone of the left femoral distal end. The animals that were administered 5mg/kg METH showed an increased locomotor activity, whereas those receiving 10mg/kg displayed an abnormal and stereotyped behavior. Serum calcium and phosphorus concentrations were normal compared to the controls, whereas the serum protein concentration was lower in the METH groups. BMD was unchanged in all groups. Bone formation markers such as alkaline phosphatase and osteocalcin significantly increased in the 5mg/kg METH group, but not in the 10mg/kg METH group. In contrast, bone resorption markers such as C-terminal telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b did not change in any of the METH groups. Histomorphometric analyses were consistent with the biochemical markers data. A significant increase in osteoblasts, especially in type III osteoblasts, was observed in the 5mg/kg METH group, whereas other parameters of bone resorption and mineralization remained unchanged. These results indicate that bone remodeling in this group was unbalanced. In contrast, in the 10mg/kg METH group, some parameters of bone formation were significantly or slightly decreased, suggesting a low turnover metabolism. Taken together, our results suggest that METH had distinct dose-dependent effects on bone turnover and that METH might induce adverse effects, leading to osteoporosis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Development of a 63K SNP array for Gossypium and high-density mapping of intra- and inter-specific populations of cotton (G. hirsutum L.)

USDA-ARS?s Scientific Manuscript database

High-throughput genotyping arrays provide a standardized resource for crop research communities that are useful for a breadth of applications including high-density genetic mapping, genome-wide association studies (GWAS), genomic selection (GS), candidate marker and quantitative trait loci (QTL) ide...

A low-density SNP array for analyzing differential selection in freshwater and marine populations of threespine stickleback (Gasterosteus aculeatus).

PubMed

Ferchaud, Anne-Laure; Pedersen, Susanne H; Bekkevold, Dorte; Jian, Jianbo; Niu, Yongchao; Hansen, Michael M

2014-10-06

The threespine stickleback (Gasterosteus aculeatus) has become an important model species for studying both contemporary and parallel evolution. In particular, differential adaptation to freshwater and marine environments has led to high differentiation between freshwater and marine stickleback populations at the phenotypic trait of lateral plate morphology and the underlying candidate gene Ectodysplacin (EDA). Many studies have focused on this trait and candidate gene, although other genes involved in marine-freshwater adaptation may be equally important. In order to develop a resource for rapid and cost efficient analysis of genetic divergence between freshwater and marine sticklebacks, we generated a low-density SNP (Single Nucleotide Polymorphism) array encompassing markers of chromosome regions under putative directional selection, along with neutral markers for background. RAD (Restriction site Associated DNA) sequencing of sixty individuals representing two freshwater and one marine population led to the identification of 33,993 SNP markers. Ninety-six of these were chosen for the low-density SNP array, among which 70 represented SNPs under putatively directional selection in freshwater vs. marine environments, whereas 26 SNPs were assumed to be neutral. Annotation of these regions revealed several genes that are candidates for affecting stickleback phenotypic variation, some of which have been observed in previous studies whereas others are new. We have developed a cost-efficient low-density SNP array that allows for rapid screening of polymorphisms in threespine stickleback. The array provides a valuable tool for analyzing adaptive divergence between freshwater and marine stickleback populations beyond the well-established candidate gene Ectodysplacin (EDA).

Development of a RAD-Seq Based DNA Polymorphism Identification Software, AgroMarker Finder, and Its Application in Rice Marker-Assisted Breeding

PubMed Central

Luo, Zhijing; Chen, Mingjiao; Zhao, Xiangxiang; Zhang, Dabing; Qi, Yiping; Yuan, Zheng

2016-01-01

Rapid and accurate genome-wide marker detection is essential to the marker-assisted breeding and functional genomics studies. In this work, we developed an integrated software, AgroMarker Finder (AMF: http://erp.novelbio.com/AMF), for providing graphical user interface (GUI) to facilitate the recently developed restriction-site associated DNA (RAD) sequencing data analysis in rice. By application of AMF, a total of 90,743 high-quality markers (82,878 SNPs and 7,865 InDels) were detected between rice varieties JP69 and Jiaoyuan5A. The density of the identified markers is 0.2 per Kb for SNP markers, and 0.02 per Kb for InDel markers. Sequencing validation revealed that the accuracy of genome-wide marker detection by AMF is 93%. In addition, a validated subset of 82 SNPs and 31 InDels were found to be closely linked to 117 important agronomic trait genes, providing a basis for subsequent marker-assisted selection (MAS) and variety identification. Furthermore, we selected 12 markers from 31 validated InDel markers to identify seed authenticity of variety Jiaoyuanyou69, and we also identified 10 markers closely linked to the fragrant gene BADH2 to minimize linkage drag for Wuxiang075 (BADH2 donor)/Jiachang1 recombinants selection. Therefore, this software provides an efficient approach for marker identification from RAD-seq data, and it would be a valuable tool for plant MAS and variety protection. PMID:26799713

Development of a RAD-Seq Based DNA Polymorphism Identification Software, AgroMarker Finder, and Its Application in Rice Marker-Assisted Breeding.

PubMed

Fan, Wei; Zong, Jie; Luo, Zhijing; Chen, Mingjiao; Zhao, Xiangxiang; Zhang, Dabing; Qi, Yiping; Yuan, Zheng

2016-01-01

Rapid and accurate genome-wide marker detection is essential to the marker-assisted breeding and functional genomics studies. In this work, we developed an integrated software, AgroMarker Finder (AMF: http://erp.novelbio.com/AMF), for providing graphical user interface (GUI) to facilitate the recently developed restriction-site associated DNA (RAD) sequencing data analysis in rice. By application of AMF, a total of 90,743 high-quality markers (82,878 SNPs and 7,865 InDels) were detected between rice varieties JP69 and Jiaoyuan5A. The density of the identified markers is 0.2 per Kb for SNP markers, and 0.02 per Kb for InDel markers. Sequencing validation revealed that the accuracy of genome-wide marker detection by AMF is 93%. In addition, a validated subset of 82 SNPs and 31 InDels were found to be closely linked to 117 important agronomic trait genes, providing a basis for subsequent marker-assisted selection (MAS) and variety identification. Furthermore, we selected 12 markers from 31 validated InDel markers to identify seed authenticity of variety Jiaoyuanyou69, and we also identified 10 markers closely linked to the fragrant gene BADH2 to minimize linkage drag for Wuxiang075 (BADH2 donor)/Jiachang1 recombinants selection. Therefore, this software provides an efficient approach for marker identification from RAD-seq data, and it would be a valuable tool for plant MAS and variety protection.

Aberrant Bone Density in Aging Mice Lacking the Adenosine Transporter ENT1

PubMed Central

Hinton, David J.; McGee-Lawrence, Meghan E.; Lee, Moonnoh R.; Kwong, Hoi K.; Westendorf, Jennifer J.; Choi, Doo-Sup

2014-01-01

Adenosine is known to regulate bone production and resorption in humans and mice. Type 1 equilibrative nucleoside transporter (ENT1) is responsible for the majority of adenosine transport across the plasma membrane and is ubiquitously expressed in both humans and mice. However, the contribution of ENT1-mediated adenosine levels has not been studied in bone remodeling. With the recent identification of the importance of adenosine signaling in bone homeostasis, it is essential to understand the role of ENT1 to develop novel therapeutic compounds for bone disorders. Here we examined the effect of ENT1 deletion on bone density using X-ray, dual energy X-ray absorptiometry and micro-computerized tomography analysis. Our results show that bone density and bone mineral density is reduced in the lower thoracic and lumbar spine as well as the femur of old ENT1 null mice (>7 months) compared to wild-type littermates. Furthermore, we found increased mRNA expression of tartrate-resistant acid phosphatase (TRAP), an osteoclast marker, in isolated long bones from 10 month old ENT1 null mice compared to wild-type mice. In addition, aged ENT1 null mice displayed severe deficit in motor coordination and locomotor activity, which might be attributed to dysregulated bone density. Overall, our study suggests that ENT1-regulated adenosine signaling plays an essential role in lumbar spine and femur bone density. PMID:24586402

On the Quality of Velocity Interpolation Schemes for Marker-In-Cell Methods on 3-D Staggered Grids

NASA Astrophysics Data System (ADS)

Kaus, B.; Pusok, A. E.; Popov, A.

2015-12-01

The marker-in-cell method is generally considered to be a flexible and robust method to model advection of heterogenous non-diffusive properties (i.e. rock type or composition) in geodynamic problems or incompressible Stokes problems. In this method, Lagrangian points carrying compositional information are advected with the ambient velocity field on an immobile, Eulerian grid. However, velocity interpolation from grid points to marker locations is often performed without preserving the zero divergence of the velocity field at the interpolated locations (i.e. non-conservative). Such interpolation schemes can induce non-physical clustering of markers when strong velocity gradients are present (Jenny et al., 2001) and this may, eventually, result in empty grid cells, a serious numerical violation of the marker-in-cell method. Solutions to this problem include: using larger mesh resolutions and/or marker densities, or repeatedly controlling the marker distribution (i.e. inject/delete), but which does not have an established physical background. To remedy this at low computational costs, Jenny et al. (2001) and Meyer and Jenny (2004) proposed a simple, conservative velocity interpolation (CVI) scheme for 2-D staggered grid, while Wang et al. (2015) extended the formulation to 3-D finite element methods. Here, we follow up with these studies and report on the quality of velocity interpolation methods for 2-D and 3-D staggered grids. We adapt the formulations from both Jenny et al. (2001) and Wang et al. (2015) for use on 3-D staggered grids, where the velocity components have different node locations as compared to finite element, where they share the same node location. We test the different interpolation schemes (CVI and non-CVI) in combination with different advection schemes (Euler, RK2 and RK4) and with/out marker control on Stokes problems with strong velocity gradients, which are discretized using a finite difference method. We show that a conservative formulation reduces the dispersion or clustering of markers and that the density of markers remains steady over time without the need of additional marker control. Jenny et al. (2001, J Comp Phys, 166, 218-252 Meyer and Jenny (2004), Proc Appl Math Mech, 4, 466-467 Wang et al. (2015), G3, Vol.16 Funding was provided by the ERC Starting Grant #258830.

Protein markers of malignant potential in penile and vulvar lichen sclerosus.

PubMed

Carlson, Bayard C; Hofer, Matthias D; Ballek, Nathaniel; Yang, Ximing J; Meeks, Joshua J; Gonzalez, Chris M

2013-08-01

Lichen sclerosus is an inflammatory skin disorder affecting anogenital areas in males and females that is associated with squamous cell carcinoma. However, there is a lack of data on the role of biomarkers for predicting lichen sclerosus progression to squamous cell carcinoma. We focused on early protein markers of squamous cell carcinoma and their expression in lichen sclerosus to improve the mechanistic and diagnostic understanding of lichen sclerosus. We performed an extensive PubMed® and MEDLINE® search for protein markers found in early stages of vulvar and penile squamous cell carcinoma, and their prevalence in associated lichen sclerosus lesions. In recent years several markers have been implicated as precursor markers for malignant transformation of lichen sclerosus into squamous cell carcinoma, including p53, Ki-67, γ-H2AX, MCM3 and cyclin D1. These proteins are up-regulated in lichen sclerosus of the vulva/penis and squamous cell carcinoma. Various levels of evidence show an association between lichen sclerosus and squamous cell carcinoma. p16 is over expressed in penile and vulvar squamous cell carcinoma associated with human papillomavirus infection but conflicting reports exist about its expression in lichen sclerosus. The angiogenesis markers vascular endothelial growth factor and cyclooxygenase-2 are expressed at higher levels, and microvessel density is increased in vulvar lichen sclerosus and squamous cell carcinoma, indicating a possible similar association in penile lichen sclerosus. Only a minority of lichen sclerosus cases are associated with squamous cell carcinoma. However, the therapeutic implications of a squamous cell carcinoma diagnosis are severe. Clinically, we lack an understanding of how to separate indolent lichen sclerosus cases from those in danger of progression to squamous cell carcinoma. Several protein markers show promise for further delineating the pathobiology of lichen sclerosus and the potential malignant transformation into squamous cell carcinoma. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Choline-stabilized orthosilicic acid supplementation as an adjunct to Calcium/Vitamin D3 stimulates markers of bone formation in osteopenic females: a randomized, placebo-controlled trial

PubMed Central

Spector, Tim D; Calomme, Mario R; Anderson, Simon H; Clement, Gail; Bevan, Liisa; Demeester, Nathalie; Swaminathan, Rami; Jugdaohsingh, Ravin; Berghe, Dirk A Vanden; Powell, Jonathan J

2008-01-01

Background Mounting evidence supports a physiological role for silicon (Si) as orthosilicic acid (OSA, Si(OH)4) in bone formation. The effect of oral choline-stabilized orthosilicic acid (ch-OSA) on markers of bone turnover and bone mineral density (BMD) was investigated in a double-blind placebo-controlled trial. Methods Over 12-months, 136 women out of 184 randomized (T-score spine < -1.5) completed the study and received, daily, 1000 mg Ca and 20 μg cholecalciferol (Vit D3) and three different ch-OSA doses (3, 6 and 12 mg Si) or placebo. Bone formation markers in serum and urinary resorption markers were measured at baseline, and after 6 and 12 months. Femoral and lumbar BMD were measured at baseline and after 12 months by DEXA. Results Overall, there was a trend for ch-OSA to confer some additional benefit to Ca and Vit D3 treatment, especially for markers of bone formation, but only the marker for type I collagen formation (PINP) was significant at 12 months for the 6 and 12 mg Si dose (vs. placebo) without a clear dose response effect. A trend for a dose-corresponding increase was observed in the bone resorption marker, collagen type I C-terminal telopeptide (CTX-I). Lumbar spine BMD did not change significantly. Post-hoc subgroup analysis (baseline T-score femur < -1) however was significant for the 6 mg dose at the femoral neck (T-test). There were no ch-OSA related adverse events observed and biochemical safety parameters remained within the normal range. Conclusion Combined therapy of ch-OSA and Ca/Vit D3 had a potential beneficial effect on bone collagen compared to Ca/Vit D3 alone which suggests that this treatment is of potential use in osteoporosis. NTR 1029 PMID:18547426

A cross-sectional study to evaluate the association of hyperbilirubinaemia on markers of cardiovascular disease, neurocognitive function, bone mineral density and renal markers in HIV-1 infected subjects on protease inhibitors.

PubMed

Barber, T J; Moyle, G; Hill, A; Jagjit Singh, G; Scourfield, A; Yapa, H M; Waters, L; Asboe, D; Boffito, M; Nelson, M

2016-05-01

Ongoing inflammation in controlled HIV infection contributes to non-AIDS comorbidities. High bilirubin appears to exhibit an anti-inflammatory effect in vivo. We therefore examined whether increased bilirubin in persons with HIV was associated with differences in markers of inflammation and cardiovascular, bone, renal disease, and neurocognitive (NC) impairment. This cross-sectional study examined inflammatory markers in individuals with stable HIV infection treated with two nucleoside reverse transcriptase inhibitors and a boosted protease inhibitor. Individuals recruited were those with a normal bilirubin (NBR; 0-17 μmol/L) or high bilirubin (>2.5 × upper limit of normal). Demographic and anthropological data were recorded. Blood and urine samples were taken for analyses. Pulse wave velocity (PWV) measurement, carotid intimal thickness (CIT), and calcaneal stiffness (CSI) were measured. Males were asked to answer a questionnaire about sexual function; NC testing was performed using CogState. 101 patients were screened, 78 enrolled (43 NBR and 35 HBR). Atazanavir use was significantly higher in HBR. Whilst a trend for lower CIT was seen in those with HBR, no significant differences were seen in PWV, bone markers, calculated cardiovascular risk (Framingham), or erectile dysfunction score. VCAM-1 levels were significantly lower in the HBR group. HBR was associated with lower LDL and triglyceride levels. NBR was associated with a calculated FRAX significantly lower than HBR although no associations were found after adjusting for tenofovir use. No difference in renal markers was observed. Component tests of NC testing revealed differences favouring HBR but overall composite scores were similar. High bilirubin in the context of boosted PI therapy was found not to be associated with differences in with the markers examined in this study. Some trends were noted and, on the basis of these, a larger, clinical end point study is warranted.

Linkage disequilibrium compared between five populations of domestic sheep.

PubMed

Meadows, Jennifer R S; Chan, Eva K F; Kijas, James W

2008-09-30

The success of genome-wide scans depends on the strength and magnitude of linkage disequilibrium (LD) present within the populations under investigation. High density SNP arrays are currently in development for the sheep genome, however little is known about the behaviour of LD in this livestock species. This study examined the behaviour of LD within five sheep populations using two LD metrics, D' and x2'. Four economically important Australian sheep flocks, three pure breeds (White Faced Suffolk, Poll Dorset, Merino) and a crossbred population (Merino x Border Leicester), along with an inbred Australian Merino museum flock were analysed. Short range LD (0 - 5 cM) was observed in all five populations, however the persistence with increasing distance and magnitude of LD varied considerably between populations. Average LD (x2') for markers spaced up to 20 cM exceeded the non-syntenic average within the White Faced Suffolk, Poll Dorset and Macarthur Merino. LD decayed faster within the Merino and Merino x Border Leicester, with LD below or consistent with observed background levels. Using marker-marker LD as a guide to the behaviour of marker-QTL LD, estimates of minimum marker spacing were made. For a 95% probability of detecting QTL, a microsatellite marker would be required every 0.1 - 2.5 centimorgans, depending on the population used. Sheep populations were selected which were inbred (Macarthur Merino), highly heterogeneous (Merino) or intermediate between these two extremes. This facilitated analysis and comparison of LD (x2') between populations. The strength and magnitude of LD was found to differ markedly between breeds and aligned closely with both observed levels of genetic diversity and expectations based on breed history. This confirmed that breed specific information is likely to be important for genome wide selection and during the design of successful genome scans where tens of thousands of markers will be required.

Oxidative stress and triglycerides as predictors of subclinical atherosclerosis in prediabetes.

PubMed

Al-Aubaidy, Hayder A; Jelinek, Herbert F

2014-03-01

The role of triglycerides in early preclinical atherosclerosis is controversial. Antioxidant markers may be associated with triglyceride levels in early preclinical atherosclerosis especially when fasting plasma glucose is raised. This cross-sectional study included 127 participants attending the Diabetes Screening Clinic, Charles Sturt University, Australia. Serum 8-hydroxy-2-deoxy-guanosine (8-OHdG) was significantly greater in the impaired fasting glucose (IFG) group compared with the control group (536.7 pg/ml ± 249.8 versus 171.4 pg/ml ± 96.9, respectively). The increase in 8-OHdG was associated with a mildly non-significant elevation in low-density lipoprotein level (3.2 ± 1.1 mmol/l) and a poor level of high-density lipoprotein (1.31 ± 0.3 mmol/l) in the IFG group. However, a significant increase in triglycerides (1.6 ± 0.97 mmol/l; P < 0.05) in the IFG group was observed. Erythrocyte reduced glutathione (GSH) levels in the IFG group, although increased, were also not significantly different to control. A significant increase in 8-OHdG is associated with increased levels of triglycerides in the absence of significant changes in reduced GSH and normal levels of cholesterol in the IFG cohort, suggesting that oxidative stress may be present and indicative of subclinical atherosclerosis.

First High-Density Linkage Map and Single Nucleotide Polymorphisms Significantly Associated With Traits of Economic Importance in Yellowtail Kingfish Seriola lalandi.

PubMed

Nguyen, Nguyen H; Rastas, Pasi M A; Premachandra, H K A; Knibb, Wayne

2018-01-01

The genetic resources available for the commercially important fish species Yellowtail kingfish (YTK) ( Seriola lalandi) are relative sparse. To overcome this, we aimed (1) to develop a linkage map for this species, and (2) to identify markers/variants associated with economically important traits in kingfish (with an emphasis on body weight). Genetic and genomic analyses were conducted using 13,898 single nucleotide polymorphisms (SNPs) generated from a new high-throughput genotyping by sequencing platform, Diversity Arrays Technology (DArTseq TM ) in a pedigreed population comprising 752 animals. The linkage analysis enabled to map about 4,000 markers to 24 linkage groups (LGs), with an average density of 3.4 SNPs per cM. The linkage map was integrated into a genome-wide association study (GWAS) and identified six variants/SNPs associated with body weight ( P < 5e -8 ) when a multi-locus mixed model was used. Two out of the six significant markers were mapped to LGs 17 and 23, and collectively they explained 5.8% of the total genetic variance. It is concluded that the newly developed linkage map and the significantly associated markers with body weight provide fundamental information to characterize genetic architecture of growth-related traits in this population of YTK S. lalandi .

A comprehensive map of the porcine genome.

PubMed

Rohrer, G A; Alexander, L J; Hu, Z; Smith, T P; Keele, J W; Beattie, C W

1996-05-01

We report the highest density genetic linkage map for a livestock species produced to date. Three published maps for Sus scrofa were merged by genotyping virtually every publicly available microsatellite across a single reference population to yield 1042 linked loci, 536 of which are novel assignments, spanning 2286.2 cM (average interval 2.23 cM) in 19 linkage groups (18 autosomal and X chromosomes, n = 19). Linkage groups were constructed de novo and mapped by locus content to avoid propagation of errors in older genotypes. The physical and genetic maps were integrated with 123 informative loci assigned previously by fluorescence in situ hybridization (FISH). Fourteen linkage groups span the entire length of each chromosome. Coverage of chromosomes 11, 12, 15, and 18 will be evaluated as more markers are physically assigned. Marker-deficient regions were identified only on 11q1.7-qter and 14 cen-q1.2. Recombination rates (cM/Mbp) varied between and within chromosomes. Short chromosomal arms recombined at higher rates than long arms, and recombination was more frequent in telomeric regions than in pericentric regions. The high-resolution comprehensive map has the marker density needed to identify quantitative trait loci (QTL), implement marker-assisted selection or introgression and YAC contig construction or chromosomal microdissection.

High-density ddRAD linkage and yield-related QTL mapping delimits a chromosomal region responsible for oil content in rapeseed (Brassica napus L.).

PubMed

Chen, Jun; Wang, Bo; Zhang, Yueli; Yue, Xiaopeng; Li, Zhaohong; Liu, Kede

2017-06-01

Rapeseed ( Brassica napus L.) is one of the most important oil crops almost all over the world. Seed-related traits, including oil content (OC), silique length (SL), seeds per silique (SS), and seed weight (SW), are primary targets for oil yield improvement. To dissect the genetic basis of these traits, 192 recombinant inbred lines (RILs) were derived from two parents with distinct oil content and silique length. High-density linkage map with a total length of 1610.4 cM were constructed using 1,329 double-digestion restriction site associated DNA (ddRAD) markers, 107 insertion/deletions (INDELs), and 90 well-distributed simple sequence repeats (SSRs) markers. A total of 37 consensus quantitative trait loci (QTLs) were detected for the four traits, with individual QTL explained 3.1-12.8% of the phenotypic variations. Interestingly, one OC consensus QTL ( cqOCA10b ) on chromosome A10 was consistently detected in all three environments, and explained 9.8% to 12.8% of the OC variation. The locus was further delimited into an approximately 614 kb genomic region, in which the flanking markers could be further evaluated for marker-assisted selection in rapeseed OC improvement and the candidate genes targeted for map-based cloning and genetic manipulation.

Characterization of a Wheat Breeders' Array suitable for high-throughput SNP genotyping of global accessions of hexaploid bread wheat (Triticum aestivum).

PubMed

Allen, Alexandra M; Winfield, Mark O; Burridge, Amanda J; Downie, Rowena C; Benbow, Harriet R; Barker, Gary L A; Wilkinson, Paul A; Coghill, Jane; Waterfall, Christy; Davassi, Alessandro; Scopes, Geoff; Pirani, Ali; Webster, Teresa; Brew, Fiona; Bloor, Claire; Griffiths, Simon; Bentley, Alison R; Alda, Mark; Jack, Peter; Phillips, Andrew L; Edwards, Keith J

2017-03-01

Targeted selection and inbreeding have resulted in a lack of genetic diversity in elite hexaploid bread wheat accessions. Reduced diversity can be a limiting factor in the breeding of high yielding varieties and crucially can mean reduced resilience in the face of changing climate and resource pressures. Recent technological advances have enabled the development of molecular markers for use in the assessment and utilization of genetic diversity in hexaploid wheat. Starting with a large collection of 819 571 previously characterized wheat markers, here we describe the identification of 35 143 single nucleotide polymorphism-based markers, which are highly suited to the genotyping of elite hexaploid wheat accessions. To assess their suitability, the markers have been validated using a commercial high-density Affymetrix Axiom ® genotyping array (the Wheat Breeders' Array), in a high-throughput 384 microplate configuration, to characterize a diverse global collection of wheat accessions including landraces and elite lines derived from commercial breeding communities. We demonstrate that the Wheat Breeders' Array is also suitable for generating high-density genetic maps of previously uncharacterized populations and for characterizing novel genetic diversity produced by mutagenesis. To facilitate the use of the array by the wheat community, the markers, the associated sequence and the genotype information have been made available through the interactive web site 'CerealsDB'. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Androgenic action of dehydroepiandrosterone (DHEA) on nerve density in the ovariectomized rat vagina.

PubMed

Pelletier, Georges; Ouellet, Johanne; Martel, Céline; Labrie, Fernand

2013-08-01

We have recently reported that dehydroepiandrosterone (DHEA) increases the density of nerve fibers in the ovariectomized (OVX) rat vagina. To better define the mechanism of action of DHEA, we have examined the effect of DHEA, conjugated estrogens (premarin) and the potent blocker of estrogen action acolbifene on the innervation in the lamina propria in the OVX rat vagina. Female Sprague-Dawley rats (10-12 weeks old) were used. Innervation of the vagina was examined 9 months after OVX and was compared to that of OVX animals treated daily with DHEA (80 mg/kg) by topical application on the skin, premarin (0.5 mg/kg) orally as well as acolbifene (2.5 mg/kg) orally administrated alone or in combination with DHEA or premarin. Four histological sections from each vagina (5 animals/group) were immunostained using antibodies to the panneuronal marker protein gene product 9.5 (PGP 9.5). The areas were measured by stereological analysis. OVX reduced the area of the lamina propria to 44% of the intact value, an effect which was reversed to 69% and 84% of the intact value by DHEA and premarin, respectively, at the doses used. When acolbifene was used, no inhibition of the stimulatory effect of DHEA was observed, while the action of premarin was completely blocked. Evaluation of the PGP 9.5 fiber density revealed that DHEA treatment increased the density of fibers by 60% compared to OVX animals, while a further 27% increase was observed when acolbifene was combined with DHEA. Premarin, on the other hand, had no effect on the density of PGP 9.5 fibers. Considering that the antiestrogen acolbifene had no inhibitory effect on the effect of DHEA in rat vagina while blocking the stimulatory effect of premarin, the present data indicate that DHEA exerts its stimulatory effect on the fiber density through an androgenic action. © 2013 International Society for Sexual Medicine.

Intradialytic aerobic cycling exercise alleviates inflammation and improves endothelial progenitor cell count and bone density in hemodialysis patients.

PubMed

Liao, Min-Tser; Liu, Wen-Chih; Lin, Fu-Huang; Huang, Ching-Feng; Chen, Shao-Yuan; Liu, Chuan-Chieh; Lin, Shih-Hua; Lu, Kuo-Cheng; Wu, Chia-Chao

2016-07-01

Inflammation, endothelial dysfunction, and mineral bone disease are critical factors contributing to morbidity and mortality in hemodialysis (HD) patients. Physical exercise alleviates inflammation and increases bone density. Here, we investigated the effects of intradialytic aerobic cycling exercise on HD patients. Forty end-stage renal disease patients undergoing HD were randomly assigned to either an exercise or control group. The patients in the exercise group performed a cycling program consisting of a 5-minute warm-up, 20 minutes of cycling at the desired workload, and a 5-minute cool down during 3 HD sessions per week for 3 months. Biochemical markers, inflammatory cytokines, nutritional status, the serum endothelial progenitor cell (EPC) count, bone mineral density, and functional capacity were analyzed. After 3 months of exercise, the patients in the exercise group showed significant improvements in serum albumin levels, the body mass index, inflammatory cytokine levels, and the number of cells positive for CD133, CD34, and kinase insert domain-conjugating receptor. Compared with the exercise group, the patients in the control group showed a loss of bone density at the femoral neck and no increases in EPCs. The patients in the exercise group also had a significantly greater 6-minute walk distance after completing the exercise program. Furthermore, the number of EPCs significantly correlated with the 6-minute walk distance both before and after the 3-month program. Intradialytic aerobic cycling exercise programs can effectively alleviate inflammation and improve nutrition, bone mineral density, and exercise tolerance in HD patients.

Effects of Dietary Supplementation with Brazil Nuts on Microvascular Endothelial Function in Hypertensive and Dyslipidemic Patients: A Randomized Crossover Placebo-Controlled Trial.

PubMed

Huguenin, Grazielle V B; Moreira, Annie S B; Siant'Pierre, Tatiana D; Gonçalves, Rodrigo A; Rosa, Glorimar; Oliveira, Glaucia M M; Luiz, Ronir R; Tibirica, Eduardo

2015-11-01

To investigate the effects of dietary supplementation with GBNs on microvascular endothelial function in hypertensive and dyslipidemic patients. Ninety-one patients of both sexes aged 62.1 ± 9.3 years received 13 g/day of GBNs or a placebo for three months with a washout period of one month between treatments. Microvascular endothelial function was assessed using LSCI coupled with iontophoresis of ACh and PORH. We also used skin video capillaroscopy to measure capillary density and recruitment at rest and during PORH. Plasma concentrations of NOx were also measured as a marker of nitric oxide bioavailability. Supplementation with GBNs significantly increased the plasma levels of Se (p < 0.05) and NOx (p < 0.05). However, we did not observe any effects of GBN consumption on microvascular vasodilator responses to ACh or PORH (p > 0.05), and GBNs did not improve capillary density at baseline or recruitment during PORH (p > 0.05). Supplementation with GBNs induced significant increases in the plasma Se concentration and systemic bioavailability of nitric oxide. Nevertheless, GBN supplementation did not lead to any improvement in systemic microvascular reactivity or density in patients with arterial hypertension and dyslipidemia who were undergoing multiple drug therapies. © 2015 John Wiley & Sons Ltd.

High-density genetic linkage map construction by F2 populations and QTL analysis of early-maturity traits in upland cotton (Gossypium hirsutum L.).

PubMed

Li, Libei; Zhao, Shuqi; Su, Junji; Fan, Shuli; Pang, Chaoyou; Wei, Hengling; Wang, Hantao; Gu, Lijiao; Zhang, Chi; Liu, Guoyuan; Yu, Dingwei; Liu, Qibao; Zhang, Xianlong; Yu, Shuxun

2017-01-01

Due to China's rapidly increasing population, the total arable land area has dramatically decreased; as a consequence, the competition for farming land allocated for grain and cotton production has become fierce. Therefore, to overcome the existing contradiction between cotton grain and fiber production and the limited farming land, development of early-maturing cultivars is necessary. In this research, a high-density linkage map of upland cotton was constructed using genotyping by sequencing (GBS) to discover single nucleotide polymorphism (SNP) markers associated with early maturity in 170 F2 individuals derived from a cross between LU28 and ZHONG213. The high-density genetic map, which was composed of 3978 SNP markers across the 26 cotton chromosomes, spanned 2480 cM with an average genetic distance of 0.62 cM. Collinearity analysis showed that the genetic map was of high quality and accurate and agreed well with the Gossypium hirsutum reference genome. Based on this high-density linkage map, QTL analysis was performed on cotton early-maturity traits, including FT, FBP, WGP, NFFB, HNFFB and PH. A total 47 QTLs for the six traits were detected; each of these QTLs explained between 2.61% and 32.57% of the observed phenotypic variation. A major region controlling early-maturity traits in Gossypium hirsutum was identified for FT, FBP, WGP, NFFB and HNFFB on chromosome D03. QTL analyses revealed that phenotypic variation explained (PVE) ranged from 10.42% to 32.57%. Two potential candidate genes, Gh_D03G0885 and Gh_D03G0922, were predicted in a stable QTL region and had higher expression levels in the early-maturity variety ZHONG213 than in the late-maturity variety LU28. However, further evidence is required for functional validation. This study could provide useful information for the dissection of early-maturity traits and guide valuable genetic loci for molecular-assisted selection (MAS) in cotton breeding.

High-density genetic linkage map construction by F2 populations and QTL analysis of early-maturity traits in upland cotton (Gossypium hirsutum L.)

PubMed Central

Li, Libei; Zhao, Shuqi; Su, Junji; Fan, Shuli; Pang, Chaoyou; Wei, Hengling; Wang, Hantao; Gu, Lijiao; Zhang, Chi; Liu, Guoyuan; Yu, Dingwei; Liu, Qibao; Zhang, Xianlong

2017-01-01

Due to China’s rapidly increasing population, the total arable land area has dramatically decreased; as a consequence, the competition for farming land allocated for grain and cotton production has become fierce. Therefore, to overcome the existing contradiction between cotton grain and fiber production and the limited farming land, development of early-maturing cultivars is necessary. In this research, a high-density linkage map of upland cotton was constructed using genotyping by sequencing (GBS) to discover single nucleotide polymorphism (SNP) markers associated with early maturity in 170 F2 individuals derived from a cross between LU28 and ZHONG213. The high-density genetic map, which was composed of 3978 SNP markers across the 26 cotton chromosomes, spanned 2480 cM with an average genetic distance of 0.62 cM. Collinearity analysis showed that the genetic map was of high quality and accurate and agreed well with the Gossypium hirsutum reference genome. Based on this high-density linkage map, QTL analysis was performed on cotton early-maturity traits, including FT, FBP, WGP, NFFB, HNFFB and PH. A total 47 QTLs for the six traits were detected; each of these QTLs explained between 2.61% and 32.57% of the observed phenotypic variation. A major region controlling early-maturity traits in Gossypium hirsutum was identified for FT, FBP, WGP, NFFB and HNFFB on chromosome D03. QTL analyses revealed that phenotypic variation explained (PVE) ranged from 10.42% to 32.57%. Two potential candidate genes, Gh_D03G0885 and Gh_D03G0922, were predicted in a stable QTL region and had higher expression levels in the early-maturity variety ZHONG213 than in the late-maturity variety LU28. However, further evidence is required for functional validation. This study could provide useful information for the dissection of early-maturity traits and guide valuable genetic loci for molecular-assisted selection (MAS) in cotton breeding. PMID:28809947

Isolating the impact of septic systems on fecal pollution in streams of suburban watersheds in Georgia, United States.

PubMed

Sowah, Robert A; Habteselassie, Mussie Y; Radcliffe, David E; Bauske, Ellen; Risse, Mark

2017-01-01

The presence of multiple sources of fecal pollution at the watershed level presents challenges to efforts aimed at identifying the influence of septic systems. In this study multiple approaches including targeted sampling and monitoring of host-specific Bacteroidales markers were used to identify the impact of septic systems on microbial water quality. Twenty four watersheds with septic density ranging from 8 to 373 septic units/km 2 were monitored for water quality under baseflow conditions over a 3-year period. The levels of the human-associated HF183 marker, as well as total and ruminant Bacteroidales, were quantified using quantitative polymerase chain reaction. Human-associated Bacteroidales yield was significantly higher in high density watersheds compared to low density areas and was negatively correlated (r = -0.64) with the average distance of septic systems to streams in the spring season. The human marker was also positively correlated with the total Bacteroidales marker, suggesting that the human source input was a significant contributor to total fecal pollution in the study area. Multivariable regression analysis indicates that septic systems, along with forest cover, impervious area and specific conductance could explain up to 74% of the variation in human fecal pollution in the spring season. The results suggest septic system impact through contributions to groundwater recharge during baseflow or failing septic system input, especially in areas with >87 septic units/km 2 . This study supports the use of microbial source tracking approaches along with traditional fecal indicator bacteria monitoring and land use characterization in a tiered approach to isolate the influence of septic systems on water quality in mixed-use watersheds. Copyright © 2016 Elsevier Ltd. All rights reserved.

Properties of Dental Pulp-derived Mesenchymal Stem Cells and the Effects of Culture Conditions.

PubMed

Kawashima, Nobuyuki; Noda, Sonoko; Yamamoto, Mioko; Okiji, Takashi

2017-09-01

Dental pulp mesenchymal stem cells (DPMSCs) highly express mesenchymal stem cell markers and possess the potential to differentiate into neural cells, osteoblasts, adipocytes, and chondrocytes. Thus, DPMSCs are considered suitable for tissue regeneration. The colony isolation method has commonly been used to collect relatively large amounts of heterogeneous DPMSCs. Homogenous DPMSCs can be isolated by fluorescence-activated cell sorting using antibodies against mesenchymal stem cell markers, although this method yields a limited number of cells. Both quality and quantity of DPMSCs are critical to regenerative therapy, and cell culture methods need to be improved. We thus investigated the properties of DPMSCs cultured with different methods. DPMSCs in a three-dimensional spheroid culture system, which is similar to the hanging drop culture for differentiation of embryonic stem cells, showed upregulation of odonto-/osteoblastic markers and mineralized nodule formation. This suggests that this three-dimensional spheroid culturing system for DPMSCs may be suitable for inducing hard tissues. We further examined the effect of cell culture density on the properties of DPMSCs because the properties of stem cells can be altered depending on the cell density. DPMSCs cultured under the confluent cell density condition showed slight downregulation of some mesenchymal stem cell markers compared with those under the sparse condition. The ability of DPMSCs to differentiate into hard tissue-forming cells was found to be enhanced in the confluent condition, suggesting that the confluent culture condition may not be suitable for maintaining the stemness of DPMSCs. When DPMSCs are to be used for hard tissue regeneration, dense followed by sparse cell culture conditions may be a better alternative strategy. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

A High-Density Genetic Map of Tetraploid Salix matsudana Using Specific Length Amplified Fragment Sequencing (SLAF-seq)

PubMed Central

Li, Min; Li, Yujuan; Wang, Ying; Ma, Xiangjian; Zhang, Yuan; Tan, Feng; Wu, Rongling

2016-01-01

As a salt-tolerant arbor tree species, Salix matsudana plays an important role in afforestation and greening in the coastal areas of China. To select superior Salix varieties that adapt to wide saline areas, it is of paramount importance to understand and identify the mechanisms of salt-tolerance at the level of the whole genome. Here, we describe a high-density genetic linkage map of S. matsudana that represents a good coverage of the Salix genome. An intraspecific F1 hybrid population was established by crossing the salt-sensitive “Yanjiang” variety as the female parent with the salt-tolerant “9901” variety as the male parent. This population, along with its parents, was genotyped by specific length amplified fragment sequencing (SLAF-seq), leading to 277,333 high-quality SLAF markers. By marker analysis, we found that both the parents and offspring were tetraploid. The mean sequencing depth was 53.20-fold for “Yanjiang”, 47.41-fold for “9901”, and 11.02-fold for the offspring. Of the SLAF markers detected, 42,321 are polymorphic with sufficient quality for map construction. The final genetic map was constructed using 6,737 SLAF markers, covering 38 linkage groups (LGs). The genetic map spanned 5,497.45 cM in length, with an average distance of 0.82 cM. As a first high-density genetic map of S. matsudana constructed from salt tolerance-varying varieties, this study will provide a foundation for mapping quantitative trait loci that modulate salt tolerance and resistance in Salix and provide important references for molecular breeding of this important forest tree. PMID:27327501

Skin Antiageing and Systemic Redox Effects of Supplementation with Marine Collagen Peptides and Plant-Derived Antioxidants: A Single-Blind Case-Control Clinical Study

PubMed Central

De Luca, Chiara; Mikhal'chik, Elena V.; Suprun, Maxim V.; Papacharalambous, Michael; Truhanov, Arseniy I.; Korkina, Liudmila G.

2016-01-01

Recently, development and research of nutraceuticals based on marine collagen peptides (MCPs) have been growing due to their high homology with human collagens, safety, bioavailability through gut, and numerous bioactivities. The major concern regarding safety of MCPs intake relates to increased risk of oxidative stress connected with collagen synthesis (likewise in fibrosis) and to ROS production by MCPs-stimulated phagocytes. In this clinical-laboratory study, fish skin MCPs combined with plant-derived skin-targeting antioxidants (AO) (coenzyme Q10 + grape-skin extract + luteolin + selenium) were administered to volunteers (n = 41). Skin properties (moisture, elasticity, sebum production, and biological age) and ultrasonic markers (epidermal/dermal thickness and acoustic density) were measured thrice (2 months before treatment and before and after cessation of 2-month oral intake). The supplementation remarkably improved skin elasticity, sebum production, and dermal ultrasonic markers. Metabolic data showed significant increase of plasma hydroxyproline and ATP storage in erythrocytes. Redox parameters, GSH/coenzyme Q10 content, and GPx/GST activities were unchanged, while NO and MDA were moderately increased within, however, normal range of values. Conclusions. A combination of MCPs with skin-targeting AOs could be effective and safe supplement to improve skin properties without risk of oxidative damage. PMID:26904164

Submucosal neurons and enteric glial cells expressing the P2X7 receptor in rat experimental colitis.

PubMed

da Silva, Marcos Vinícius; Marosti, Aline Rosa; Mendes, Cristina Eusébio; Palombit, Kelly; Castelucci, Patricia

2017-06-01

The aim of this study was to evaluate the effect of ulcerative colitis on the submucosal neurons and glial cells of the submucosal ganglia of rats. 2,4,6-Trinitrobenzene sulfonic acid (TNBS; colitis group) was administered in the colon to induce ulcerative colitis, and distal colons were collected after 24h. The colitis rats were compared with those in the sham and control groups. Double labelling of the P2X7 receptor with calbindin (marker for intrinsic primary afferent neurons, IPANs, submucosal plexus), calretinin (marker for secretory and vasodilator neurons of the submucosal plexus), HuC/D and S100β was performed in the submucosal plexus. The density (neurons per area) of submucosal neurons positive for the P2X7 receptor, calbindin, calretinin and HuC/D decreased by 21%, 34%, 8.2% and 28%, respectively, in the treated group. In addition, the density of enteric glial cells in the submucosal plexus decreased by 33%. The profile areas of calbindin-immunoreactive neurons decreased by 25%. Histological analysis revealed increased lamina propria and decreased collagen in the colitis group. This study demonstrated that ulcerative colitis affected secretory and vasodilatory neurons, IPANs and enteric glia of the submucosal plexus expressing the P2X7 receptor. Copyright © 2017 Elsevier GmbH. All rights reserved.

A consensus linkage map for molecular markers and Quantitative Trait Loci associated with economically important traits in melon (Cucumis melo L.)

PubMed Central

2011-01-01

Background A number of molecular marker linkage maps have been developed for melon (Cucumis melo L.) over the last two decades. However, these maps were constructed using different marker sets, thus, making comparative analysis among maps difficult. In order to solve this problem, a consensus genetic map in melon was constructed using primarily highly transferable anchor markers that have broad potential use for mapping, synteny, and comparative quantitative trait loci (QTL) analysis, increasing breeding effectiveness and efficiency via marker-assisted selection (MAS). Results Under the framework of the International Cucurbit Genomics Initiative (ICuGI, http://www.icugi.org), an integrated genetic map has been constructed by merging data from eight independent mapping experiments using a genetically diverse array of parental lines. The consensus map spans 1150 cM across the 12 melon linkage groups and is composed of 1592 markers (640 SSRs, 330 SNPs, 252 AFLPs, 239 RFLPs, 89 RAPDs, 15 IMAs, 16 indels and 11 morphological traits) with a mean marker density of 0.72 cM/marker. One hundred and ninety-six of these markers (157 SSRs, 32 SNPs, 6 indels and 1 RAPD) were newly developed, mapped or provided by industry representatives as released markers, including 27 SNPs and 5 indels from genes involved in the organic acid metabolism and transport, and 58 EST-SSRs. Additionally, 85 of 822 SSR markers contributed by Syngenta Seeds were included in the integrated map. In addition, 370 QTL controlling 62 traits from 18 previously reported mapping experiments using genetically diverse parental genotypes were also integrated into the consensus map. Some QTL associated with economically important traits detected in separate studies mapped to similar genomic positions. For example, independently identified QTL controlling fruit shape were mapped on similar genomic positions, suggesting that such QTL are possibly responsible for the phenotypic variability observed for this trait in a broad array of melon germplasm. Conclusions Even though relatively unsaturated genetic maps in a diverse set of melon market types have been published, the integrated saturated map presented herein should be considered the initial reference map for melon. Most of the mapped markers contained in the reference map are polymorphic in diverse collection of germplasm, and thus are potentially transferrable to a broad array of genetic experimentation (e.g., integration of physical and genetic maps, colinearity analysis, map-based gene cloning, epistasis dissection, and marker-assisted selection). PMID:21797998

A consensus linkage map for molecular markers and quantitative trait loci associated with economically important traits in melon (Cucumis melo L.).

PubMed

Diaz, Aurora; Fergany, Mohamed; Formisano, Gelsomina; Ziarsolo, Peio; Blanca, José; Fei, Zhanjun; Staub, Jack E; Zalapa, Juan E; Cuevas, Hugo E; Dace, Gayle; Oliver, Marc; Boissot, Nathalie; Dogimont, Catherine; Pitrat, Michel; Hofstede, René; van Koert, Paul; Harel-Beja, Rotem; Tzuri, Galil; Portnoy, Vitaly; Cohen, Shahar; Schaffer, Arthur; Katzir, Nurit; Xu, Yong; Zhang, Haiying; Fukino, Nobuko; Matsumoto, Satoru; Garcia-Mas, Jordi; Monforte, Antonio J

2011-07-28

A number of molecular marker linkage maps have been developed for melon (Cucumis melo L.) over the last two decades. However, these maps were constructed using different marker sets, thus, making comparative analysis among maps difficult. In order to solve this problem, a consensus genetic map in melon was constructed using primarily highly transferable anchor markers that have broad potential use for mapping, synteny, and comparative quantitative trait loci (QTL) analysis, increasing breeding effectiveness and efficiency via marker-assisted selection (MAS). Under the framework of the International Cucurbit Genomics Initiative (ICuGI, http://www.icugi.org), an integrated genetic map has been constructed by merging data from eight independent mapping experiments using a genetically diverse array of parental lines. The consensus map spans 1150 cM across the 12 melon linkage groups and is composed of 1592 markers (640 SSRs, 330 SNPs, 252 AFLPs, 239 RFLPs, 89 RAPDs, 15 IMAs, 16 indels and 11 morphological traits) with a mean marker density of 0.72 cM/marker. One hundred and ninety-six of these markers (157 SSRs, 32 SNPs, 6 indels and 1 RAPD) were newly developed, mapped or provided by industry representatives as released markers, including 27 SNPs and 5 indels from genes involved in the organic acid metabolism and transport, and 58 EST-SSRs. Additionally, 85 of 822 SSR markers contributed by Syngenta Seeds were included in the integrated map. In addition, 370 QTL controlling 62 traits from 18 previously reported mapping experiments using genetically diverse parental genotypes were also integrated into the consensus map. Some QTL associated with economically important traits detected in separate studies mapped to similar genomic positions. For example, independently identified QTL controlling fruit shape were mapped on similar genomic positions, suggesting that such QTL are possibly responsible for the phenotypic variability observed for this trait in a broad array of melon germplasm. Even though relatively unsaturated genetic maps in a diverse set of melon market types have been published, the integrated saturated map presented herein should be considered the initial reference map for melon. Most of the mapped markers contained in the reference map are polymorphic in diverse collection of germplasm, and thus are potentially transferrable to a broad array of genetic experimentation (e.g., integration of physical and genetic maps, colinearity analysis, map-based gene cloning, epistasis dissection, and marker-assisted selection).

A consensus linkage map of lentil based on DArT markers from three RIL mapping populations.

PubMed

Ates, Duygu; Aldemir, Secil; Alsaleh, Ahmad; Erdogmus, Semih; Nemli, Seda; Kahriman, Abdullah; Ozkan, Hakan; Vandenberg, Albert; Tanyolac, Bahattin

2018-01-01

Lentil (Lens culinaris ssp. culinaris Medikus) is a diploid (2n = 2x = 14), self-pollinating grain legume with a haploid genome size of about 4 Gbp and is grown throughout the world with current annual production of 4.9 million tonnes. A consensus map of lentil (Lens culinaris ssp. culinaris Medikus) was constructed using three different lentils recombinant inbred line (RIL) populations, including "CDC Redberry" x "ILL7502" (LR8), "ILL8006" x "CDC Milestone" (LR11) and "PI320937" x "Eston" (LR39). The lentil consensus map was composed of 9,793 DArT markers, covered a total of 977.47 cM with an average distance of 0.10 cM between adjacent markers and constructed 7 linkage groups representing 7 chromosomes of the lentil genome. The consensus map had no gap larger than 12.67 cM and only 5 gaps were found to be between 12.67 cM and 6.0 cM (on LG3 and LG4). The localization of the SNP markers on the lentil consensus map were in general consistent with their localization on the three individual genetic linkage maps and the lentil consensus map has longer map length, higher marker density and shorter average distance between the adjacent markers compared to the component linkage maps. This high-density consensus map could provide insight into the lentil genome. The consensus map could also help to construct a physical map using a Bacterial Artificial Chromosome library and map based cloning studies. Sequence information of DArT may help localization of orientation scaffolds from Next Generation Sequencing data.

A SNP based high-density linkage map of Apis cerana reveals a high recombination rate similar to Apis mellifera.

PubMed

Shi, Yuan Yuan; Sun, Liang Xian; Huang, Zachary Y; Wu, Xiao Bo; Zhu, Yong Qiang; Zheng, Hua Jun; Zeng, Zhi Jiang

2013-01-01

The Eastern honey bee, Apis cerana Fabricius, is distributed in southern and eastern Asia, from India and China to Korea and Japan and southeast to the Moluccas. This species is also widely kept for honey production besides Apis mellifera. Apis cerana is also a model organism for studying social behavior, caste determination, mating biology, sexual selection, and host-parasite interactions. Few resources are available for molecular research in this species, and a linkage map was never constructed. A linkage map is a prerequisite for quantitative trait loci mapping and for analyzing genome structure. We used the Chinese honey bee, Apis cerana cerana to construct the first linkage map in the Eastern honey bee. F2 workers (N = 103) were genotyped for 126,990 single nucleotide polymorphisms (SNPs). After filtering low quality and those not passing the Mendel test, we obtained 3,000 SNPs, 1,535 of these were informative and used to construct a linkage map. The preliminary map contains 19 linkage groups, we then mapped the 19 linkage groups to 16 chromosomes by comparing the markers to the genome of A. mellfiera. The final map contains 16 linkage groups with a total of 1,535 markers. The total genetic distance is 3,942.7 centimorgans (cM) with the largest linkage group (180 loci) measuring 574.5 cM. Average marker interval for all markers across the 16 linkage groups is 2.6 cM. We constructed a high density linkage map for A. c. cerana with 1,535 markers. Because the map is based on SNP markers, it will enable easier and faster genotyping assays than randomly amplified polymorphic DNA or microsatellite based maps used in A. mellifera.

A consensus linkage map of lentil based on DArT markers from three RIL mapping populations

PubMed Central

Ates, Duygu; Aldemir, Secil; Alsaleh, Ahmad; Erdogmus, Semih; Nemli, Seda; Kahriman, Abdullah; Ozkan, Hakan; Vandenberg, Albert

2018-01-01

Background Lentil (Lens culinaris ssp. culinaris Medikus) is a diploid (2n = 2x = 14), self-pollinating grain legume with a haploid genome size of about 4 Gbp and is grown throughout the world with current annual production of 4.9 million tonnes. Materials and methods A consensus map of lentil (Lens culinaris ssp. culinaris Medikus) was constructed using three different lentils recombinant inbred line (RIL) populations, including “CDC Redberry” x “ILL7502” (LR8), “ILL8006” x “CDC Milestone” (LR11) and “PI320937” x “Eston” (LR39). Results The lentil consensus map was composed of 9,793 DArT markers, covered a total of 977.47 cM with an average distance of 0.10 cM between adjacent markers and constructed 7 linkage groups representing 7 chromosomes of the lentil genome. The consensus map had no gap larger than 12.67 cM and only 5 gaps were found to be between 12.67 cM and 6.0 cM (on LG3 and LG4). The localization of the SNP markers on the lentil consensus map were in general consistent with their localization on the three individual genetic linkage maps and the lentil consensus map has longer map length, higher marker density and shorter average distance between the adjacent markers compared to the component linkage maps. Conclusion This high-density consensus map could provide insight into the lentil genome. The consensus map could also help to construct a physical map using a Bacterial Artificial Chromosome library and map based cloning studies. Sequence information of DArT may help localization of orientation scaffolds from Next Generation Sequencing data. PMID:29351563

A rat genetic map constructed by representational difference analysis markers with suitability for large-scale typing.

PubMed Central

Toyota, M; Canzian, F; Ushijima, T; Hosoya, Y; Kuramoto, T; Serikawa, T; Imai, K; Sugimura, T; Nagao, M

1996-01-01

Representational difference analysis (RDA) was applied to isolate chromosomal markers in the rat. Four series of RDA [restriction enzymes, BamHI and HindIII; subtraction of ACI/N (ACI) amplicon from BUF/Nac (BUF) amplicon and vice versa] yielded 131 polymorphic markers; 125 of these markers were mapped to all chromosomes except for chromosome X. This was done by using a mapping panel of 105 ACI x BUF F2 rats. To complement the relative paucity of chromosomal markers in the rat, genetically directed RDA, which allows isolation of polymorphic markers in the specific chromosomal region, was performed. By changing the F2 driver-DNA allele frequency around the region, four markers were isolated from the D1Ncc1 locus. Twenty-five of 27 RDA markers were informative regarding the dot blot analysis of amplicons, hybridizing only with tester amplicons. Dot blot analysis at a high density per unit of area made it possible to process a large number of samples. Quantitative trait loci can now be mapped in the rat genome by processing a large number of samples with RDA markers and then by isolating markers close to the loci of interest by genetically directed RDA. Images Fig. 1 Fig. 3 Fig. 4 PMID:8632989

Thermo-mechanical properties of W/Mo markers coatings deposited on bulk W

NASA Astrophysics Data System (ADS)

Grigore, E.; Ruset, C.; Gherendi, M.; Chioibasu, D.; Hakola, A.; contributors, JET

2016-02-01

In the present paper marker structures consisting of W/Mo layers were deposited on bulk W samples by using a modified CMSII method. This technology, compared to standard CMSII, prevents the formation of nano-pore structures at interfaces. The thicknesses of the markers were in the range 20-35 μm to balance the requirements associated with the wall erosion in ITER and thermo-mechanical performances. The coatings structure and composition were evaluated by glow discharge optical emission spectrometry (GDOES), and energy dispersive x-ray spectroscopy measurements (EDX). The adhesion of the coatings to the substrate has been assessed by scratch test method. In order to evaluate their effectiveness as potential markers for fusion applications, the marker coatings have been tested in an electron beam facility at a temperature of 1000 °C and a power density of about 3 MW m-2. A number of 300 pulses with duration of 420 s (35 testing hours) were applied on the marker coated samples.

Predictive Value of Early Tumor Shrinkage and Density Reduction of Lung Metastases in Patients With Metastatic Colorectal Cancer Treated With Regorafenib.

PubMed

Vanwynsberghe, Hannes; Verbeke, Xander; Coolen, Johan; Van Cutsem, Eric

2017-12-01

The benefit of regorafenib in colorectal cancer is not very pronounced. At present, there is lack of predictive biological or radiological markers. We studied if density reduction or small changes in size of lung metastases could be a predictive marker. We retrospectively measured density in size of lung metastases of all patients included in the CORRECT and CONSIGN trials at our center. Contrast-enhanced CT scan at baseline and at week 8 were compared. Data of progressive-free survival and overall survival were collected from the CORRECT and CONSIGN trials. A significant difference in progressive-free survival was seen in 3 groups: response or stable disease in size (5.36 vs. 3.96 months), response in density (6.03 vs. 2.72 months), and response in corrected density (6.14 vs. 3.08 months). No difference was seen for response in size versus stable disease or progressive disease in size. For overall survival, a difference was observed in the same 3 groups: response or stable disease in size (9.89 vs. 6.44 months), response in density (9.59 vs. 7.04 months), and response in corrected density (9.09 vs. 7.16 months). No difference was seen for response in size versus stable disease or progressive disease in size. Density reduction in lung metastases might be a good predictive parameter to predict outcome for regorafenib. Early tumor progression might be a negative predictive factor. If further validated, density reduction and early tumor progression might be useful to ameliorate the cost-benefit of regorafenib. Copyright © 2017 Elsevier Inc. All rights reserved.

First trimester maternal lipid levels and serum markers of small- and large-for-gestational age infants.

PubMed

Parlakgumus, Huriye Ayse; Aytac, Pinar Caglar; Kalaycı, Hakan; Tarim, Ebru

2014-01-01

To investigate if first trimester lipids, sonographic parameters and serum markers are related to small- and large-for-gestational age (SGA, LGA) infants. This study was conducted at Baskent University Adana Research Center between December 2009 and July 2011 and enrolled 433 women. Blood samples were drawn to measure fasting blood glucose, serum triglycerides, cholesterol, very low-density lipoprotein, low-density lipoprotein, high-density lipoprotein, fβ-hCG and pregnancy associated protein-A (PAPP-A) at the first trimester. Crown rump length and nuchal translucency were measured as suggested by the fetal medicine foundation. LGA group was significantly taller (p = 0.016) and SGA group had significantly greater BMI (0.025). SGA fetuses were born at a significantly earlier gestational age (p = 0.001). Univariate analysis revealed that LGA group had significantly lower cholesterol (p = 0.038) and LDL levels (p = 0.041). PAPP-A was significantly lower in SGA Group compared with LGA Group (0.027). After controlling for age, parity, height, pre-pregnant BMI, weight gain during pregnancy and fasting blood sugar, none of the lipids, serum markers or sonographic parameters was related to LGA. PAPP-A was the only parameter significantly associated with SGA after multivariate analysis (p = 0.008). PAPP-A was significantly associated with SGA after controlling for confounders.

Comparative analysis of microsatellites in five different antagonistic Trichoderma species for diversity assessment.

PubMed

Rai, Shalini; Kashyap, Prem Lal; Kumar, Sudheer; Srivastava, Alok Kumar; Ramteke, Pramod W

2016-01-01

Microsatellites provide an ideal molecular markers system to screen, characterize and evaluate genetic diversity of several fungal species. Currently, there is very limited information on the genetic diversity of antagonistic Trichoderma species as determined using a range of molecular markers. In this study, expressed and whole genome sequences available in public database were used to investigate the occurrence, relative abundance and relative density of SSRs in five different antagonistic Trichoderma species: Trichoderma atroviride, T. harzianum, T. reesei, T. virens and T. asperellum. Fifteen SSRs loci were used to evaluate genetic diversity of twenty isolates of Trichoderma spp. from different geographical regions of India. Results indicated that relative abundance and relative density of SSRs were higher in T. asperellum followed by T. reesei and T. atroviride. Tri-nucleotide repeats (80.2%) were invariably the most abundant in all species. The abundance and relative density of SSRs were not influenced by the genome sizes and GC content. Out of eighteen primer sets, only 15 primer pairs showed successful amplification in all the test species. A total of 24 alleles were detected and five loci were highly informative with polymorphism information content values greater than 0.40, these markers provide useful information on genetic diversity and population genetic structure, which, in turn, can exploit for establishing conservation strategy for antagonistic Trichoderma isolates.

Effects of Holding Time, Storage, and the Preservation of ...

EPA Pesticide Factsheets

The purpose of this project was to answer questions related to storage of samples to be analyzed by the quantitative polymerase chain reaction (qPCR)-based assays for fecal indicator bacteria. The project was divided into two parts. The first part was to determine if filters that were used to collect fecal indicators could be stored frozen and analyzed at a later date and the second part was to determine if refrigerated water samples could be held for 24 to 48 hours prior to analysis by qPCR. Both of these studies answer questions that were important in the analysis of fresh and marine surface water samples for beach monitoring purposes. 1) Develop and evaluate qPCR assays and test methods for the detection and quantification of genetic markers from indicator bacteria that are associated with human fecal waste and from two new groups of general fecal indicator bacteria (E. coli and Clostridia) that historically have been widely used or are favored in specific regions 2) Determine the occurrence and densities of genetic markers detected by new qPCR assays developed under objective 1 and compare with occurrence and densities of genetic markers detected by previously developed qPCR assays for enterococci and total Bacterioidalesin waste waters and fecal material from different animal sources. 3) Determine stability of fecal indicator bacteria target DNA sequences in freezer archived filter retentates of ambient surface water samples 4) Determine the densitie

Treatment of low bone density in young people with cystic fibrosis: a multicentre, prospective, open-label observational study of calcium and calcifediol followed by a randomised placebo-controlled trial of alendronate.

PubMed

Bianchi, Maria Luisa; Colombo, Carla; Assael, Baroukh M; Dubini, Antonella; Lombardo, Mariangela; Quattrucci, Serena; Bella, Sergio; Collura, Mirella; Messore, Barbara; Raia, Valeria; Poli, Furio; Bini, Rita; Albanese, Carlina V; De Rose, Virginia; Costantini, Diana; Romano, Giovanna; Pustorino, Elena; Magazzù, Giuseppe; Bertasi, Serenella; Lucidi, Vincenzina; Traverso, Gabriella; Coruzzo, Anna; Grzejdziak, Amelia D

2013-07-01

Long-term complications of cystic fibrosis include osteoporosis and fragility fractures, but few data are available about effective treatment strategies, especially in young patients. We investigated treatment of low bone mineral density in children, adolescents, and young adults with cystic fibrosis. We did a multicentre trial in two phases. We enrolled patients aged 5-30 years with cystic fibrosis and low bone mineral density, from ten cystic fibrosis regional centres in Italy. The first phase was an open-label, 12-month observational study of the effect of adequate calcium intake plus calcifediol. The second phase was a 12-month, double-blind, randomised, placebo-controlled, parallel group study of the efficacy and safety of oral alendronate in patients whose bone mineral apparent density had not increased by 5% or more by the end of the observational phase. Patients were randomly assigned to either alendronate or placebo. Both patients and investigators were masked to treatment assignment. We used dual x-ray absorptiometry at baseline and every 6 months thereafter, corrected for body size, to assess lumbar spine bone mineral apparent density. We assessed bone turnover markers and other laboratory parameters every 3-6 months. The primary endpoint was mean increase of lumbar spine bone mineral apparent density, assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01812551. We screened 540 patients and enrolled 171 (mean age 13·8 years, SD 5·9, range 5-30). In the observational phase, treatment with calcium and calcifediol increased bone mineral apparent density by 5% or more in 43 patients (25%). 128 patients entered the randomised phase. Bone mineral apparent density increased by 16·3% in the alendronate group (n=65) versus 3·1% in the placebo group (n=63; p=0·0010). 19 of 57 young people (33·3%) receiving alendronate attained a normal-for-age bone mineral apparent density Z score. In the observational phase, five patients had moderate episodes of hypercalciuria, which resolved after short interruption of calcifediol treatment. During the randomised phase, one patient taking alendronate had mild fever versus none in the placebo group; treatment groups did not differ significantly for other adverse events. Correct calcium intake plus calcifediol can improve bone mineral density in some young patients with cystic fibrosis. In those who do not respond to calcium and calcifediol alone, alendronate can safely and effectively increase bone mineral density. Telethon Foundation (Italy). Copyright © 2013 Elsevier Ltd. All rights reserved.

Total Xenoestrogen Body Burden in Relation to Mammographic Density, a Marker of Breast Cancer Risk

DTIC Science & Technology

2008-10-01

average, how often do you eat a serving of meat, including beef , chicken, lamb, or pork? Never or less than once per month 1-3 servings per...has been obtained from the Susan Komen Foundation for an ancillary study of sex hormones and breast density. The Komen Foundation is providing funds...to analyze sex hormone levels in the blood samples obtained in this study. The relation between sex hormone levels and mammographic breast density

[Serum sclerostin levels and metabolic bone diseases].

PubMed

Yamauchi, Mika; Sugimoto, Toshitsugu

2013-06-01

Serum sclerostin levels are being investigated in various metabolic bone diseases. Since serum sclerostin levels are decreased in primary hyperparathyroidism and elevated in hypoparathyroidism, parathyroid hormone (PTH) is thought to be a regulatory factor for sclerostin. Serum sclerostin levels exhibit a significant positive correlation with bone mineral density. On the other hand, a couple of studies on postmenopausal women have shown that high serum sclerostin levels are a risk factor for fracture. Although glucocorticoid induced osteoporosis and diabetes are both diseases that reduce bone formation, serum sclerostin levels have been reported to be decreased in the former and elevated in the latter, suggesting differences in the effects of sclerostin in the two diseases. Serum sclerostin levels are correlated with renal function, and increase with reduction in renal function. Serum sclerostin level may be a new index of bone assessment that differs from bone mineral density and bone metabolic markers.

Development and use of molecular markers: past and present.

PubMed

Grover, Atul; Sharma, P C

2016-01-01

Molecular markers, due to their stability, cost-effectiveness and ease of use provide an immensely popular tool for a variety of applications including genome mapping, gene tagging, genetic diversity diversity, phylogenetic analysis and forensic investigations. In the last three decades, a number of molecular marker techniques have been developed and exploited worldwide in different systems. However, only a handful of these techniques, namely RFLPs, RAPDs, AFLPs, ISSRs, SSRs and SNPs have received global acceptance. A recent revolution in DNA sequencing techniques has taken the discovery and application of molecular markers to high-throughput and ultrahigh-throughput levels. Although, the choice of marker will obviously depend on the targeted use, microsatellites, SNPs and genotyping by sequencing (GBS) largely fulfill most of the user requirements. Further, modern transcriptomic and functional markers will lead the ventures onto high-density genetic map construction, identification of QTLs, breeding and conservation strategies in times to come in combination with other high throughput techniques. This review presents an overview of different marker technologies and their variants with a comparative account of their characteristic features and applications.

Development of new SNP derived cleaved amplified polymorphic sequence marker set and its successful utilization in the genetic analysis of seed color variation in barley.

PubMed

Bungartz, Annemarie; Klaus, Marius; Mathew, Boby; Léon, Jens; Naz, Ali Ahmad

2016-03-01

The aim of the present study was to develop a new cost effective PCR based CAPS marker set using advantages of high-throughput SNP genotyping. Initially, SNP survey was made using 20 diverse barley genotypes via 9k iSelect array genotyping that resulted in 6334 polymorphic SNP markers. Principle component analysis using this marker data showed fine differentiation of barley diverse gene pool. Till this end, we developed 200 SNP derived CAPS markers distributed across the genome covering around 991cM with an average marker density of 5.09cM. Further, we genotyped 68 CAPS markers in an F2 population (Cheri×ICB181160) segregating for seed color variation in barley. Genetic mapping of seed color revealed putative linkage of single nuclear gene on chromosome 1H. These findings showed the proof of concept for the development and utility of a newer cost effective genomic tool kit to analyze broader genetic resources of barley worldwide. Copyright © 2016 Elsevier Inc. All rights reserved.

Curcumin Chemosensitizes 5-Fluorouracil Resistant MMR-Deficient Human Colon Cancer Cells in High Density Cultures

PubMed Central

Shakibaei, Mehdi; Buhrmann, Constanze; Kraehe, Patricia; Shayan, Parviz; Lueders, Cora; Goel, Ajay

2014-01-01

Objective Treatment of colorectal cancer (CRC) remains a clinical challenge, as more than 15% of patients are resistant to 5-Fluorouracil (5-FU)-based chemotherapeutic regimens, and tumor recurrence rates can be as high as 50–60%. Cancer stem cells (CSC) are capable of surviving conventional chemotherapies that permits regeneration of original tumors. Therefore, we investigated the effectiveness of 5-FU and plant polyphenol (curcumin) in context of DNA mismatch repair (MMR) status and CSC activity in 3D cultures of CRC cells. Methods High density 3D cultures of CRC cell lines HCT116, HCT116+ch3 (complemented with chromosome 3) and their corresponding isogenic 5-FU-chemo-resistant derivative clones (HCT116R, HCT116+ch3R) were treated with 5-FU either without or with curcumin in time- and dose-dependent assays. Results Pre-treatment with curcumin significantly enhanced the effect of 5-FU on HCT116R and HCR116+ch3R cells, in contrast to 5-FU alone as evidenced by increased disintegration of colonospheres, enhanced apoptosis and by inhibiting their growth. Curcumin and/or 5-FU strongly affected MMR-deficient CRC cells in high density cultures, however MMR-proficient CRC cells were more sensitive. These effects of curcumin in enhancing chemosensitivity to 5-FU were further supported by its ability to effectively suppress CSC pools as evidenced by decreased number of CSC marker positive cells, highlighting the suitability of this 3D culture model for evaluating CSC marker expression in a close to vivo setting. Conclusion Our results illustrate novel and previously unrecognized effects of curcumin in enhancing chemosensitization to 5-FU-based chemotherapy on DNA MMR-deficient and their chemo-resistant counterparts by targeting the CSC sub-population. (246 words in abstract). PMID:24404205

Curcumin chemosensitizes 5-fluorouracil resistant MMR-deficient human colon cancer cells in high density cultures.

PubMed

Shakibaei, Mehdi; Buhrmann, Constanze; Kraehe, Patricia; Shayan, Parviz; Lueders, Cora; Goel, Ajay

2014-01-01

Treatment of colorectal cancer (CRC) remains a clinical challenge, as more than 15% of patients are resistant to 5-Fluorouracil (5-FU)-based chemotherapeutic regimens, and tumor recurrence rates can be as high as 50-60%. Cancer stem cells (CSC) are capable of surviving conventional chemotherapies that permits regeneration of original tumors. Therefore, we investigated the effectiveness of 5-FU and plant polyphenol (curcumin) in context of DNA mismatch repair (MMR) status and CSC activity in 3D cultures of CRC cells. High density 3D cultures of CRC cell lines HCT116, HCT116+ch3 (complemented with chromosome 3) and their corresponding isogenic 5-FU-chemo-resistant derivative clones (HCT116R, HCT116+ch3R) were treated with 5-FU either without or with curcumin in time- and dose-dependent assays. Pre-treatment with curcumin significantly enhanced the effect of 5-FU on HCT116R and HCR116+ch3R cells, in contrast to 5-FU alone as evidenced by increased disintegration of colonospheres, enhanced apoptosis and by inhibiting their growth. Curcumin and/or 5-FU strongly affected MMR-deficient CRC cells in high density cultures, however MMR-proficient CRC cells were more sensitive. These effects of curcumin in enhancing chemosensitivity to 5-FU were further supported by its ability to effectively suppress CSC pools as evidenced by decreased number of CSC marker positive cells, highlighting the suitability of this 3D culture model for evaluating CSC marker expression in a close to vivo setting. Our results illustrate novel and previously unrecognized effects of curcumin in enhancing chemosensitization to 5-FU-based chemotherapy on DNA MMR-deficient and their chemo-resistant counterparts by targeting the CSC sub-population. (246 words in abstract).

Study of Autophagy and Microangiopathy in Sural Nerves of Patients with Chronic Idiopathic Axonal Polyneuropathy

PubMed Central

Samuelsson, Kristin; Osman, Ayman A. M.; Angeria, Maria; Risling, Mårten; Mohseni, Simin; Press, Rayomand

2016-01-01

Twenty-five percent of polyneuropathies are idiopathic. Microangiopathy has been suggested to be a possible pathogenic cause of chronic idiopathic axonal polyneuropathy (CIAP). Dysfunction of the autophagy pathway has been implicated as a marker of neurodegeneration in the central nervous system, but the autophagy process is not explored in the peripheral nervous system. In the current study, we examined the presence of microangiopathy and autophagy-related structures in sural nerve biopsies of 10 patients with CIAP, 11 controls with inflammatory neuropathy and 10 controls without sensory polyneuropathy. We did not find any significant difference in endoneurial microangiopathic markers in patients with CIAP compared to normal controls, though we did find a correlation between basal lamina area thickness and age. Unexpectedly, we found a significantly larger basal lamina area thickness in patients with vasculitic neuropathy. Furthermore, we found a significantly higher density of endoneurial autophagy-related structures, particularly in patients with CIAP but also in patients with inflammatory neuropathy, compared to normal controls. It is unclear if the alteration in the autophagy pathway is a consequence or a cause of the neuropathy. Our results do not support the hypothesis that CIAP is primarily caused by a microangiopathic process in endoneurial blood vessels in peripheral nerves. The significantly higher density of autophagy structures in sural nerves obtained from patients with CIAP and inflammatory neuropathy vs. controls indicates the involvement of this pathway in neuropathy, particularly in CIAP, since the increase in density of autophagy-related structures was more pronounced in patients with CIAP than those with inflammatory neuropathy. To our knowledge this is the first report investigating signs of autophagy process in peripheral nerves in patients with CIAP and inflammatory neuropathy. PMID:27662650

Centromere Locations in Brassica A and C Genomes Revealed Through Half-Tetrad Analysis

PubMed Central

Mason, Annaliese S.; Rousseau-Gueutin, Mathieu; Morice, Jérôme; Bayer, Philipp E.; Besharat, Naghmeh; Cousin, Anouska; Pradhan, Aneeta; Parkin, Isobel A. P.; Chèvre, Anne-Marie; Batley, Jacqueline; Nelson, Matthew N.

2016-01-01

Locating centromeres on genome sequences can be challenging. The high density of repetitive elements in these regions makes sequence assembly problematic, especially when using short-read sequencing technologies. It can also be difficult to distinguish between active and recently extinct centromeres through sequence analysis. An effective solution is to identify genetically active centromeres (functional in meiosis) by half-tetrad analysis. This genetic approach involves detecting heterozygosity along chromosomes in segregating populations derived from gametes (half-tetrads). Unreduced gametes produced by first division restitution mechanisms comprise complete sets of nonsister chromatids. Along these chromatids, heterozygosity is maximal at the centromeres, and homologous recombination events result in homozygosity toward the telomeres. We genotyped populations of half-tetrad-derived individuals (from Brassica interspecific hybrids) using a high-density array of physically anchored SNP markers (Illumina Brassica 60K Infinium array). Mapping the distribution of heterozygosity in these half-tetrad individuals allowed the genetic mapping of all 19 centromeres of the Brassica A and C genomes to the reference Brassica napus genome. Gene and transposable element density across the B. napus genome were also assessed and corresponded well to previously reported genetic map positions. Known centromere-specific sequences were located in the reference genome, but mostly matched unanchored sequences, suggesting that the core centromeric regions may not yet be assembled into the pseudochromosomes of the reference genome. The increasing availability of genetic markers physically anchored to reference genomes greatly simplifies the genetic and physical mapping of centromeres using half-tetrad analysis. We discuss possible applications of this approach, including in species where half-tetrads are currently difficult to isolate. PMID:26614742

Centromere Locations in Brassica A and C Genomes Revealed Through Half-Tetrad Analysis.

PubMed

Mason, Annaliese S; Rousseau-Gueutin, Mathieu; Morice, Jérôme; Bayer, Philipp E; Besharat, Naghmeh; Cousin, Anouska; Pradhan, Aneeta; Parkin, Isobel A P; Chèvre, Anne-Marie; Batley, Jacqueline; Nelson, Matthew N

2016-02-01

Locating centromeres on genome sequences can be challenging. The high density of repetitive elements in these regions makes sequence assembly problematic, especially when using short-read sequencing technologies. It can also be difficult to distinguish between active and recently extinct centromeres through sequence analysis. An effective solution is to identify genetically active centromeres (functional in meiosis) by half-tetrad analysis. This genetic approach involves detecting heterozygosity along chromosomes in segregating populations derived from gametes (half-tetrads). Unreduced gametes produced by first division restitution mechanisms comprise complete sets of nonsister chromatids. Along these chromatids, heterozygosity is maximal at the centromeres, and homologous recombination events result in homozygosity toward the telomeres. We genotyped populations of half-tetrad-derived individuals (from Brassica interspecific hybrids) using a high-density array of physically anchored SNP markers (Illumina Brassica 60K Infinium array). Mapping the distribution of heterozygosity in these half-tetrad individuals allowed the genetic mapping of all 19 centromeres of the Brassica A and C genomes to the reference Brassica napus genome. Gene and transposable element density across the B. napus genome were also assessed and corresponded well to previously reported genetic map positions. Known centromere-specific sequences were located in the reference genome, but mostly matched unanchored sequences, suggesting that the core centromeric regions may not yet be assembled into the pseudochromosomes of the reference genome. The increasing availability of genetic markers physically anchored to reference genomes greatly simplifies the genetic and physical mapping of centromeres using half-tetrad analysis. We discuss possible applications of this approach, including in species where half-tetrads are currently difficult to isolate. Copyright © 2016 by the Genetics Society of America.

A natural product telomerase activator as part of a health maintenance program: metabolic and cardiovascular response.

PubMed

Harley, Calvin B; Liu, Weimin; Flom, Peter L; Raffaele, Joseph M

2013-10-01

A short average telomere length is associated with low telomerase activity and certain degenerative diseases. Studies in animals and with human cells confirm a causal mechanism for cell or tissue dysfunction triggered by critically short telomeres, suggesting that telomerase activation may be an approach to health maintenance. Previously, we reported on positive immune remodeling in humans taking a commercial health maintenance program, PattonProtocol-1, composed of TA-65® (a natural product-derived telomerase activator) and other dietary supplements. In over a 5-year period and an estimated 7000 person-years of use, no adverse events or effects have been attributed to TA-65 by physicians licensed to sell the product. Here we report on changes in metabolic markers measured at baseline (n=97-107 subjects) and every 3-6 months (n=27-59 subjects) during the first 12 months of study. Rates of change per year from baseline determined by a multi-level model were -3.72 mg/dL for fasting glucose (p=0.02), -1.32 mIU/mL for insulin (p=0.01), -13.2 and -11.8 mg/dL for total cholesterol and low-density lipoprotein cholesterol (LDL-C) (p=0.002, p=0.002, respectively), -17.3 and -4.2 mmHg for systolic and diastolic blood pressure (p=0.007 and 0.001, respectively), and -3.6 μmole/L homocysteine (p=0.001). In a subset of individuals with bone mineral density (BMD) measured at baseline and 12 months, density increased 2.0% in the spine (p=0.003). We conclude that in addition to apparent positive immune remodeling, PattonProtocol-1 may improve markers of metabolic, bone, and cardiovascular health.

Effect of Non-Surgical Periodontal Treatment on Clinical and Biochemical Risk Markers of Cardiovascular Disease: A Randomized Trial.

PubMed

Hada, Divya Singh; Garg, Subhash; Ramteke, Girish B; Ratre, Madhu Singh

2015-11-01

Various studies have shown periodontal disease is one of the risk factors for coronary heart disease (CHD), and periodontal treatment of patients with CHD has also been correlated with reduction in systemic markers of CHD. The aim of this study is to evaluate the effect of non-surgical periodontal treatment (NSPT) on the cardiovascular clinical and biochemical status of patients with CHD. Seventy known patients with CHD were allocated randomly to either a control group (C; no periodontal therapy) (n = 35) or an experimental group (E; NSPT in the form of scaling and root planing [SRP]) (n = 35). Cardiovascular status was assessed using clinical parameters such as pulse, respiratory rate, blood pressure (BP), and biochemical parameters, such as high-sensitivity C-reactive protein (hsCRP), lipid profile, and white blood cell (WBC) count, at baseline and 1, 3, and 6 months. Intergroup and intragroup comparisons were performed using Student t test, and P <0.05 was considered statistically significant. The complete data at the end of the study were provided by only 55 patients (group C, n = 25; group E, n = 30). Highly statistically significant reduction was observed in systolic BP (7.1 mm Hg) and very-low-density lipoproteins (VLDLs; 5.16 mg/dL) in group E. Changes were also observed in other cardiovascular biochemical and clinical parameters but were not statistically significant. NSPT (in the form of SRP) positively affects limited cardiovascular (clinical and biochemical) status of patients with CHD. Reduction in triglyceride, VLDL, total WBC, lymphocyte, and neutrophil counts and increase in hsCRP, total cholesterol, high-density lipoprotein, and low-density lipoprotein levels were observed. Highly significant reduction in VLDL cholesterol levels and systolic BP was observed among the various parameters measured.

Prenatal exposure to ethanol stimulates hypothalamic CCR2 chemokine receptor system: Possible relation to increased density of orexigenic peptide neurons and ethanol drinking in adolescent offspring

PubMed Central

Chang, G.-Q.; Karatayev, O.; Leibowitz, S. F.

2015-01-01

Clinical and animal studies indicate that maternal consumption of ethanol during pregnancy increases alcohol drinking in the offspring. Possible underlying mechanisms may involve orexigenic peptides, which are stimulated by prenatal ethanol exposure and themselves promote drinking. Building on evidence that ethanol stimulates neuroimmune factors such as the chemokine CCL2 that in adult rats is shown to colocalize with the orexigenic peptide, melanin-concentrating hormone (MCH) in the lateral hypothalamus (LH), the present study sought to investigate the possibility that CCL2 or its receptor CCR2 in LH are stimulated by prenatal ethanol exposure, perhaps specifically within MCH neurons. Our paradigm of intraoral administration of ethanol to pregnant rats, at low-to-moderate doses (1 or 3 g/kg/day) during peak hypothalamic neurogenesis, caused in adolescent male offspring two-fold increase in drinking of and preference for ethanol and reinstatement of ethanol drinking in a two-bottle choice paradigm under an intermittent access schedule. This effect of prenatal ethanol exposure was associated with an increased expression of MCH and density of MCH+ neurons in LH of preadolescent offspring. Whereas CCL2+ cells at this age were low in density and unaffected by ethanol, CCR2+ cells were dense in LH and increased by prenatal ethanol, with a large percentage (83–87%) identified as neurons and found to colocalize MCH. Prenatal ethanol also stimulated the genesis of CCR2+ and MCH+ neurons in the embryo, which co-labeled the proliferation marker, BrdU. Ethanol also increased the genesis and density of neurons that co-expressed CCR2 and MCH in LH, with triple-labeled CCR2+/MCH+/BrdU+ neurons that were absent in control rats accounting for 35% of newly generated neurons in ethanol-exposed rats. With both the chemokine and MCH systems believed to promote ethanol consumption, this greater density of CCR2+/MCH+ neurons in the LH of preadolescent rats suggests that these systems function together in promoting alcohol drinking during adolescence. PMID:26365610

Bone Mineral Density in Boys Diagnosed with Autism Spectrum Disorder: A Case-Control Study

ERIC Educational Resources Information Center

Barnhill, Kelly; Ramirez, Lucas; Gutierrez, Alan; Richardson, Wendy; Marti, C. Nathan; Potts, Amy; Shearer, Rebeca; Schutte, Claire; Hewitson, Laura

2017-01-01

This study compared bone mineral density (BMD) of the spine obtained by dual-energy X-ray absorptiometry (DEXA), nutritional status, biochemical markers, and gastrointestinal (GI) symptoms in 4-8 year old boys with Autism Spectrum Disorder (ASD) with a group of age-matched, healthy boys without ASD. Boys with ASD had significantly lower spine BMD…

A high density linkage map of the ancestral diploid strawberry F. iinumae using SNP markers from the ISTRAW90 array and GBS

USDA-ARS?s Scientific Manuscript database

Fragaria iinumae is recognized as an ancestor of the octoploid strawberry species, including the cultivated strawberry, Fragaria ×ananassa. Here we report the construction of the first high density linkage map for F. iinumae. The map is based on two high-throughput techniques of single nucleotide p...

Genetic dissection of growth, wood basic density and gene expression in interspecific backcrosses of Eucalyptus grandis and E. urophylla

PubMed Central

2012-01-01

Background F1 hybrid clones of Eucalyptus grandis and E. urophylla are widely grown for pulp and paper production in tropical and subtropical regions. Volume growth and wood quality are priority objectives in Eucalyptus tree improvement. The molecular basis of quantitative variation and trait expression in eucalypt hybrids, however, remains largely unknown. The recent availability of a draft genome sequence (http://www.phytozome.net) and genome-wide genotyping platforms, combined with high levels of genetic variation and high linkage disequilibrium in hybrid crosses, greatly facilitate the detection of quantitative trait loci (QTLs) as well as underlying candidate genes for growth and wood property traits. In this study, we used Diversity Arrays Technology markers to assess the genetic architecture of volume growth (diameter at breast height, DBH) and wood basic density in four-year-old progeny of an interspecific backcross pedigree of E. grandis and E. urophylla. In addition, we used Illumina RNA-Seq expression profiling in the E. urophylla backcross family to identify cis- and trans-acting polymorphisms (eQTLs) affecting transcript abundance of genes underlying QTLs for wood basic density. Results A total of five QTLs for DBH and 12 for wood basic density were identified in the two backcross families. Individual QTLs for DBH and wood basic density explained 3.1 to 12.2% of phenotypic variation. Candidate genes underlying QTLs for wood basic density on linkage groups 8 and 9 were found to share trans-acting eQTLs located on linkage groups 4 and 10, which in turn coincided with QTLs for wood basic density suggesting that these QTLs represent segregating components of an underlying transcriptional network. Conclusion This is the first demonstration of the use of next-generation expression profiling to quantify transcript abundance in a segregating tree population and identify candidate genes potentially affecting wood property variation. The QTLs identified in this study provide a resource for identifying candidate genes and developing molecular markers for marker-assisted breeding of volume growth and wood basic density. Our results suggest that integrated analysis of transcript and trait variation in eucalypt hybrids can be used to dissect the molecular basis of quantitative variation in wood property traits. PMID:22817272

Water Stress Modulates Soybean Aphid Performance, Feeding Behavior, and Virus Transmission in Soybean

PubMed Central

Nachappa, Punya; Culkin, Christopher T.; Saya, Peter M.; Han, Jinlong; Nalam, Vamsi J.

2016-01-01

Little is known about how water stress including drought and flooding modifies the ability of plants to resist simultaneous attack by insect feeding and transmission of insect-vectored pathogen. We analyzed insect population growth, feeding behaviors, virus transmission, and plant amino acid profiles and defense gene expression to characterize mechanisms underlying the interaction between water stress, soybean aphid and aphid-transmitted, Soybean mosaic virus, on soybean plants. Population growth of non-viruliferous aphids was reduced under drought stress and saturation, likely because the aphids spent less time feeding from the sieve element on these plants compared to well-watered plants. Water stress did not impact population growth of viruliferous aphids. However, virus incidence and transmission rate was lowest under drought stress and highest under saturated conditions since viruliferous aphids took the greatest amount time to puncture cells and transmit the virus under saturated conditions and lowest time under drought stress. Petiole exudates from drought-stressed plants had the highest level of total free amino acids including asparagine and valine that are critical for aphid performance. Aphids did not benefit from improved phloem sap quality as indicated by their lower densities on drought-stressed plants. Saturation, on the other hand, resulted in low amino acid content compared to all of the other treatments. Drought and saturation had significant and opposing effects on expression of marker genes involved in abscisic acid (ABA) signaling. Drought alone significantly increased expression of ABA marker genes, which likely led to suppression of salicylic acid (SA)- and jasmonic acid (JA)-related genes. In contrast, ABA marker genes were down-regulated under saturation, while expression of SA- and JA-related genes was up-regulated. We propose that the apparent antagonism between ABA and SA/JA signaling pathways contributed to an increase in aphid densities under drought and their decrease under saturation. Taken together, our findings suggests that plant responses to water stress is complex involving changes in phloem amino acid composition and signaling pathways, which can impact aphid populations and virus transmission. PMID:27200027

Persister formation in Staphylococcus aureus is associated with ATP depletion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Conlon, Brian P.; Rowe, Sarah E.; Gandt, Autumn Brown

Persisters are dormant phenotypic variants of bacterial cells that are tolerant to killing by antibiotics1. Persisters are associated with chronic bacterial infection and antibiotic treatment failure. In Escherichia coli, toxin/antitoxin (TA) modules are responsible for persister formation. The mechanism of persister formation in Gram positive bacteria is unknown. Staphylococcus aureus is a major human pathogen, responsible for a variety of chronic and relapsing infections such as osteomyelitis, endocarditis and infections of implanted devices. Deleting TA modules in S. aureus did not affect the level of persisters. Here we show that S. aureus persisters are produced due to a stochastic entrancemore » to stationary phase accompanied by a drop in intracellular ATP. Cells expressing stationary state markers are present throughout the growth phase, increasing in frequency with cell density. Cell sorting revealed that expression of stationary markers was associated with a 100-1000 fold increased likelihood of survival to antibiotic challenge. We find that the antibiotic tolerance of these cells is due to a drop in intracellular ATP. The ATP level of the cell is predictive of bactericidal antibiotic efficacy and explains bacterial tolerance to antibiotic treatment.« less

Brain Creatine Elevation and NAA Reduction Indicates Neuronal Dysfunction in the Setting of Enhanced Glial Energy Metabolism in a Macaque Model of neuroAIDS

PubMed Central

Ratai, Eva-Maria; Annamalai, Lakshmanan; Burdo, Tricia; Joo, Chan-Gyu; Bombardier, Jeffrey P.; Fell, Robert; Hakimelahi, Reza; He, Julian; Lentz, Margaret R.; Campbell, Jennifer; Curran, Elizabeth; Halpern, Elkan F.; Masliah, Eliezer; Westmoreland, Susan. V.; Williams, Kenneth C.; González, R. Gilberto

2011-01-01

Proton magnetic resonance spectroscopy (1H MRS) has emerged as one of the most informative neuroimaging modalities for studying the effect of HIV infection in the brain, providing surrogate markers by which to assess disease progression and monitor treatment. Reductions in the level of N-Acetylaspartate (NAA) and NAA/creatine (NAA/Cr) are established markers of neuronal injury or loss. However, the biochemical basis of altered creatine levels in neuroAIDS is not well understood. This study used a rapid progression macaque model of neuroAIDS to elucidate the changes in creatine. As the disease progressed 1H MRS revealed a decrease in NAA, indicative of neuronal injury, and an increase in creatine yet to be elucidated. Subsequently, immunohistochemistry and stereology measures of decreased synaptophysin, microtubule-associated protein 2, and neuronal density confirmed neuronal injury. Furthermore, increases in ionized calcium binding adaptor molecule 1 and glial fibrillary acidic protein indicated microglial and astroglial activation, respectively. Given these data, elevated creatine may reflect enhanced high-energy phosphate turnover in highly metabolizing activated astrocytes and microglia. PMID:21381104

Using specific length amplified fragment sequencing to construct the high-density genetic map for Vitis (Vitis vinifera L. × Vitis amurensis Rupr.).

PubMed

Guo, Yinshan; Shi, Guangli; Liu, Zhendong; Zhao, Yuhui; Yang, Xiaoxu; Zhu, Junchi; Li, Kun; Guo, Xiuwu

2015-01-01

In this study, 149 F1 plants from the interspecific cross between 'Red Globe' (Vitis vinifera L.) and 'Shuangyou' (Vitis amurensis Rupr.) and the parent were used to construct a molecular genetic linkage map by using the specific length amplified fragment sequencing technique. DNA sequencing generated 41.282 Gb data consisting of 206,411,693 paired-end reads. The average sequencing depths were 68.35 for 'Red Globe,' 63.65 for 'Shuangyou,' and 8.01 for each progeny. In all, 115,629 high-quality specific length amplified fragments were detected, of which 42,279 were polymorphic. The genetic map was constructed using 7,199 of these polymorphic markers. These polymorphic markers were assigned to 19 linkage groups; the total length of the map was 1929.13 cm, with an average distance of 0.28 cm between each maker. To our knowledge, the genetic maps constructed in this study contain the largest number of molecular markers. These high-density genetic maps might form the basis for the fine quantitative trait loci mapping and molecular-assisted breeding of grape.

Markers of bone turnover in patients with epilepsy and their relationship to management of bone diseases induced by antiepileptic drugs.

PubMed

Hamed, Sherifa A

2016-01-01

Data from cross-sectional and prospective studies revealed that patients with epilepsy and on long-term treatment with antiepileptic drugs (AEDs) are at increased risk for metabolic bone diseases. Bone diseases were reported in about 50% of patients on AEDs. Low bone mineral density, osteopenia/osteoporosis, osteomalacia, rickets, altered concentration of bone turnover markers and fractures were reported with phenobarbital, phenytoin, carbamazepine, valproate, oxcarbazepine and lamotrigine. The mechanisms for AEDs-induced bone diseases are heterogeneous and include hypovitaminosis D, hypocalcemia and direct acceleration of bone loss and/or reduction of bone formation. This article reviews the evidence, predictors and mechanisms of AEDs-induced bone abnormalities and its clinical implications. For patients on AEDs, regular monitoring of bone health is recommended. Prophylactic administration of calcium and vitamin D is recommended for all patients. Treatment doses of calcium and vitamin D and even anti-resorptive drug therapy are reserved for patients at high risk of pathological fracture.

Undaria pinnatifida and Fucoxanthin Ameliorate Lipogenesis and Markers of Both Inflammation and Cardiovascular Dysfunction in an Animal Model of Diet-Induced Obesity.

PubMed

Grasa-López, Ameyalli; Miliar-García, Ángel; Quevedo-Corona, Lucía; Paniagua-Castro, Norma; Escalona-Cardoso, Gerardo; Reyes-Maldonado, Elba; Jaramillo-Flores, María-Eugenia

2016-08-03

Brown algae and its carotenoids have been shown to have a positive influence on obesity and its comorbidities. This study evaluated the effect of Undaria pinnatifida and fucoxanthin on biochemical, physiological and inflammation markers related to obesity and on the expression of genes engaged on white adipose tissue lipid metabolism in a murine model of diet-induced obesity. The treatments improved energy expenditure, β-oxidation and adipogenesis by upregulating PPARα, PGC1α, PPARγ and UCP-1. Adipogenesis was also confirmed by image analysis of the retroperitoneal adipose tissue, by measuring cell area, perimeter and cellular density. Additionally, the treatments, ameliorated adipose tissue accumulation, insulin resistance, blood pressure, cholesterol and triglycerides concentration in serum, and reduced lipogenesis and inflammation by downregulating acetyl-CoA carboxylase (ACC) gene expression, increasing serum concentration and expression of adiponectin as well as downregulating IL-6 expression. Both fucoxanthin and Undaria pinnatifida may be considered for treating obesity and other diseases related.

Testosterone Combined with Electrical Stimulation and Standing: Effect on Muscle and Bone

DTIC Science & Technology

2015-10-01

JJPVAMC). During year 1 of the study, the Study Team (Drs. Forrest, Bauman, and Harkema) established a new partnership with a pharmaceutical company...AbbVie) to supply Drug and Placebo for all potential study participants. Each of the study sites submitted to the pharmaceutical company all requested...stimulation, dynamic standing protocol, muscle volume, MRI , bone mineral density, DXA, QCT scans, blood markers, urine markers, 60 sessions of training

The effects of age on associations between markers of HIV progression and markers of metabolic function including albumin, haemoglobin and lipid concentrations.

PubMed

Samuel, M; Jose, S; Winston, A; Nelson, M; Johnson, M; Chadwick, D; Fisher, M; Leen, C; Gompels, M; Gilson, R; Post, F A; Hay, P; Sabin, C A

2014-05-01

We investigated whether age modified associations between markers of HIV progression, CD4 T lymphocyte count and HIV RNA viral load (VL), and the following markers of metabolic function: albumin, haemoglobin, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). A retrospective analysis of data from the United Kingdom Collaborative HIV Cohort was carried out. Analyses were limited to antiretroviral-naïve subjects to focus on the impact of HIV disease itself. A total of 16670 subjects were included in the analysis. Multilevel linear regression models assessed associations between CD4 count/VL and each of the outcomes. Statistical tests for interactions assessed whether associations differed among age groups. After adjustment for gender and ethnicity, there was evidence that lower CD4 count and higher VL were associated with lower TC, LDL-C, haemoglobin and albumin concentrations but higher triglyceride concentrations. Age modified associations between CD4 count and albumin (P < 0.001) and haemoglobin (P = 0.001), but not between CD4 count and HDL-C, LDL-C and TC, or VL and any outcome. Among participants aged < 30, 30-50 and > 50 years, a 50 cells/μL lower CD4 count correlated with a 2.4 [95% confidence interval (CI) 1.7-3.0], 3.6 (95% CI 3.2-4.0) and 5.1 (95% CI 4.0-6.1) g/L lower haemoglobin concentration and a 0.09 (95% CI 0.07-0.11), 0.12 (95% CI 0.11-0.13) and 0.16 (95% CI 0.13-0.19) g/L lower albumin concentration, respectively. We present evidence that age modifies associations between CD4 count and plasma albumin and haemoglobin levels. A given reduction in CD4 count was associated with a greater reduction in haemoglobin and albumin concentrations among older people living with HIV. These findings increase our understanding of how the metabolic impact of HIV is influenced by age. © 2013 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.

Atherogenic index of plasma: a useful marker for subclinical atherosclerosis in ankylosing spondylitis : AIP associate with cIMT in AS.

PubMed

Cure, Erkan; Icli, Abdullah; Uslu, Ali Ugur; Sakiz, Davut; Cure, Medine Cumhur; Baykara, Rabia Aydogan; Yavuz, Fatma; Arslan, Sevket; Kucuk, Adem

2018-05-01

Ankylosing spondylitis (AS) is associated with an increased risk of atherosclerotic cardiovascular disease (ACD). The atherogenic index of plasma (AIP), which is the logarithmic transformation of the plasma triglyceride (TG) level to the high-density lipoprotein level (HDL) ratio, has been suggested to be a novel marker in the identification of atherosclerosis risk. Therefore, this study aims to determine if the AIP can act as an accurate marker for the detection of subclinical atherosclerosis. Fifty-two male patients with AS and 52 age-, gender-, and body mass index (BMI)-matched healthy control subjects were included in the study. For each patient, AIP and total cholesterol (TC)/HDL values were calculated and carotid artery intima-media thickness (cIMT) was measured. The mean (SD) cIMT and median (range) AIP values for AS patients were higher than that of the healthy control subjects (0.60 ± 0.18 vs. 0.51 ± 0.10, p = 0.003 and 0.23 [- 0.32 to 0.85] vs. 0.09 [- 0.53 to 0.49], p = 0.007, respectively). A positive correlation was found between the patients' cIMT and AIP values (r = 0.307, p = 0.002) and TC/HDL values (r = 0.241, p = 0.014). Regression analysis revealed an independent association between the subclinical atherosclerosis and AIP (beta [β] = 0.309, p = 0.002). There were no independent correlations between subclinical atherosclerosis and TC (β = 0.245, p = 0.065), TG (β = 0.185, p = 0.515), HDL (β = 0.198, p = 0.231), TC/HDL (β = 0.032, p = 0.862), and low-density lipoprotein (LDL) (β = 0.151, p = 0.246). A strong and independent correlation exists between AIP and cIMT values. Therefore, the AIP could serve as a better marker than the TC/HDL ratio for the detection of subclinical atherosclerosis in AS patients.

Optimizing 4DCBCT projection allocation to respiratory bins.

PubMed

O'Brien, Ricky T; Kipritidis, John; Shieh, Chun-Chien; Keall, Paul J

2014-10-07

4D cone beam computed tomography (4DCBCT) is an emerging image guidance strategy used in radiotherapy where projections acquired during a scan are sorted into respiratory bins based on the respiratory phase or displacement. 4DCBCT reduces the motion blur caused by respiratory motion but increases streaking artefacts due to projection under-sampling as a result of the irregular nature of patient breathing and the binning algorithms used. For displacement binning the streak artefacts are so severe that displacement binning is rarely used clinically. The purpose of this study is to investigate if sharing projections between respiratory bins and adjusting the location of respiratory bins in an optimal manner can reduce or eliminate streak artefacts in 4DCBCT images. We introduce a mathematical optimization framework and a heuristic solution method, which we will call the optimized projection allocation algorithm, to determine where to position the respiratory bins and which projections to source from neighbouring respiratory bins. Five 4DCBCT datasets from three patients were used to reconstruct 4DCBCT images. Projections were sorted into respiratory bins using equispaced, equal density and optimized projection allocation. The standard deviation of the angular separation between projections was used to assess streaking and the consistency of the segmented volume of a fiducial gold marker was used to assess motion blur. The standard deviation of the angular separation between projections using displacement binning and optimized projection allocation was 30%-50% smaller than conventional phase based binning and 59%-76% smaller than conventional displacement binning indicating more uniformly spaced projections and fewer streaking artefacts. The standard deviation in the marker volume was 20%-90% smaller when using optimized projection allocation than using conventional phase based binning suggesting more uniform marker segmentation and less motion blur. Images reconstructed using displacement binning and the optimized projection allocation algorithm were clearer, contained visibly fewer streak artefacts and produced more consistent marker segmentation than those reconstructed with either equispaced or equal-density binning. The optimized projection allocation algorithm significantly improves image quality in 4DCBCT images and provides, for the first time, a method to consistently generate high quality displacement binned 4DCBCT images in clinical applications.

Gamma-glutamyltransferase activity in exosomes as a potential marker for prostate cancer.

PubMed

Kawakami, Kyojiro; Fujita, Yasunori; Matsuda, Yoko; Arai, Tomio; Horie, Kengo; Kameyama, Koji; Kato, Taku; Masunaga, Koichi; Kasuya, Yutaka; Tanaka, Masashi; Mizutani, Kosuke; Deguchi, Takashi; Ito, Masafumi

2017-05-05

Exosomes or extracellular vesicles have the potential as a diagnostic marker for various diseases including cancer. In order to identify novel exosomal markers for prostate cancer (PC), we performed proteomic analysis of exosomes isolated from PC cell lines and examined the usefulness of the marker in patients. Exosomes isolated by differential centrifugation from the culture medium of androgen-dependent LNCaP prostate cancer cell line and its sublines of partially androgen-independent C4, androgen-independent C4-2 and bone metastatic C4-2B were subjected to iTRAQ-based proteomic analysis. Exosomes were also isolated by immunocapture and separated by size exclusion chromatography and density gradient centrifugation. Protein expression was determined by Western blot analysis. GGT activity was measured using a fluorescent probe, γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG). Immunohistochemical analysis of tissues was performed using anti-GGT1 antibody. Among proteins upregulated in C4-2 and C4-2B cells than in LNCaP cells, we focused on gamma-glutamyltransferase 1 (GGT1), a cell-surface enzyme that regulates the catabolism of extracellular glutathione. The levels of both GGT1 large and small subunits were elevated in exosomes isolated from C4-2 and C4-2B cells by differential centrifugation and by immunocapture with anti-CD9 or -prostate-specific membrane antigen (PSMA) antibody. In cell lysates and exosomes, GGT1 expression correlated with GGT activity. Size exclusion chromatography of human serum demonstrated the presence of GGT activity and GGT1 subunits in fractions positive for CD9. Density gradient centrifugation revealed the co-presence of GGT1 subunits with CD9 in exosomes isolated by differential centrifugation from human serum. Since GGT activity correlated with GGT1 expression in serum exosomes isolated by differential centrifugation, we measured serum exosomal GGT activity in patients. Unexpectedly, we found that serum exosomal GGT activity was significantly higher in PC patients than in benign prostatic hyperplasia (BPH) patients. In support of this finding, immunohistochemical analysis showed increased GGT1 expression in PC tissues compared with BPH tissues. Our results suggest that serum exosomal GGT activity could be a useful biomarker for PC.

Integrated consensus genetic and physical maps of flax (Linum usitatissimum L.).

PubMed

Cloutier, Sylvie; Ragupathy, Raja; Miranda, Evelyn; Radovanovic, Natasa; Reimer, Elsa; Walichnowski, Andrzej; Ward, Kerry; Rowland, Gordon; Duguid, Scott; Banik, Mitali

2012-12-01

Three linkage maps of flax (Linum usitatissimum L.) were constructed from populations CDC Bethune/Macbeth, E1747/Viking and SP2047/UGG5-5 containing between 385 and 469 mapped markers each. The first consensus map of flax was constructed incorporating 770 markers based on 371 shared markers including 114 that were shared by all three populations and 257 shared between any two populations. The 15 linkage group map corresponds to the haploid number of chromosomes of this species. The marker order of the consensus map was largely collinear in all three individual maps but a few local inversions and marker rearrangements spanning short intervals were observed. Segregation distortion was present in all linkage groups which contained 1-52 markers displaying non-Mendelian segregation. The total length of the consensus genetic map is 1,551 cM with a mean marker density of 2.0 cM. A total of 670 markers were anchored to 204 of the 416 fingerprinted contigs of the physical map corresponding to ~274 Mb or 74 % of the estimated flax genome size of 370 Mb. This high resolution consensus map will be a resource for comparative genomics, genome organization, evolution studies and anchoring of the whole genome shotgun sequence.

Saturated linkage map construction in Rubus idaeus using genotyping by sequencing and genome-independent imputation

PubMed Central

2013-01-01

Background Rapid development of highly saturated genetic maps aids molecular breeding, which can accelerate gain per breeding cycle in woody perennial plants such as Rubus idaeus (red raspberry). Recently, robust genotyping methods based on high-throughput sequencing were developed, which provide high marker density, but result in some genotype errors and a large number of missing genotype values. Imputation can reduce the number of missing values and can correct genotyping errors, but current methods of imputation require a reference genome and thus are not an option for most species. Results Genotyping by Sequencing (GBS) was used to produce highly saturated maps for a R. idaeus pseudo-testcross progeny. While low coverage and high variance in sequencing resulted in a large number of missing values for some individuals, a novel method of imputation based on maximum likelihood marker ordering from initial marker segregation overcame the challenge of missing values, and made map construction computationally tractable. The two resulting parental maps contained 4521 and 2391 molecular markers spanning 462.7 and 376.6 cM respectively over seven linkage groups. Detection of precise genomic regions with segregation distortion was possible because of map saturation. Microsatellites (SSRs) linked these results to published maps for cross-validation and map comparison. Conclusions GBS together with genome-independent imputation provides a rapid method for genetic map construction in any pseudo-testcross progeny. Our method of imputation estimates the correct genotype call of missing values and corrects genotyping errors that lead to inflated map size and reduced precision in marker placement. Comparison of SSRs to published R. idaeus maps showed that the linkage maps constructed with GBS and our method of imputation were robust, and marker positioning reliable. The high marker density allowed identification of genomic regions with segregation distortion in R. idaeus, which may help to identify deleterious alleles that are the basis of inbreeding depression in the species. PMID:23324311

Exploiting genotyping by sequencing to characterize the genomic structure of the American cranberry through high-density linkage mapping.

PubMed

Covarrubias-Pazaran, Giovanny; Diaz-Garcia, Luis; Schlautman, Brandon; Deutsch, Joseph; Salazar, Walter; Hernandez-Ochoa, Miguel; Grygleski, Edward; Steffan, Shawn; Iorizzo, Massimo; Polashock, James; Vorsa, Nicholi; Zalapa, Juan

2016-06-13

The application of genotyping by sequencing (GBS) approaches, combined with data imputation methodologies, is narrowing the genetic knowledge gap between major and understudied, minor crops. GBS is an excellent tool to characterize the genomic structure of recently domesticated (~200 years) and understudied species, such as cranberry (Vaccinium macrocarpon Ait.), by generating large numbers of markers for genomic studies such as genetic mapping. We identified 10842 potentially mappable single nucleotide polymorphisms (SNPs) in a cranberry pseudo-testcross population wherein 5477 SNPs and 211 short sequence repeats (SSRs) were used to construct a high density linkage map in cranberry of which a total of 4849 markers were mapped. Recombination frequency, linkage disequilibrium (LD), and segregation distortion at the genomic level in the parental and integrated linkage maps were characterized for first time in cranberry. SSR markers, used as the backbone in the map, revealed high collinearity with previously published linkage maps. The 4849 point map consisted of twelve linkage groups spanning 1112 cM, which anchored 2381 nuclear scaffolds accounting for ~13 Mb of the estimated 470 Mb cranberry genome. Bin mapping identified 592 and 672 unique bins in the parentals and a total of 1676 unique marker positions in the integrated map. Synteny analyses comparing the order of anchored cranberry scaffolds to their homologous positions in kiwifruit, grape, and coffee genomes provided initial evidence of homology between cranberry and closely related species. GBS data was used to rapidly saturate the cranberry genome with markers in a pseudo-testcross population. Collinearity between the present saturated genetic map and previous cranberry SSR maps suggests that the SNP locations represent accurate marker order and chromosome structure of the cranberry genome. SNPs greatly improved current marker genome coverage, which allowed for genome-wide structure investigations such as segregation distortion, recombination, linkage disequilibrium, and synteny analyses. In the future, GBS can be used to accelerate cranberry molecular breeding through QTL mapping and genome-wide association studies (GWAS).

Using microsatellites to understand the physical distribution of recombination on soybean chromosomes.

PubMed

Ott, Alina; Trautschold, Brian; Sandhu, Devinder

2011-01-01

Soybean is a major crop that is an important source of oil and proteins. A number of genetic linkage maps have been developed in soybean. Specifically, hundreds of simple sequence repeat (SSR) markers have been developed and mapped. Recent sequencing of the soybean genome resulted in the generation of vast amounts of genetic information. The objectives of this investigation were to use SSR markers in developing a connection between genetic and physical maps and to determine the physical distribution of recombination on soybean chromosomes. A total of 2,188 SSRs were used for sequence-based physical localization on soybean chromosomes. Linkage information was used from different maps to create an integrated genetic map. Comparison of the integrated genetic linkage maps and sequence based physical maps revealed that the distal 25% of each chromosome was the most marker-dense, containing an average of 47.4% of the SSR markers and 50.2% of the genes. The proximal 25% of each chromosome contained only 7.4% of the markers and 6.7% of the genes. At the whole genome level, the marker density and gene density showed a high correlation (R(2)) of 0.64 and 0.83, respectively with the physical distance from the centromere. Recombination followed a similar pattern with comparisons indicating that recombination is high in telomeric regions, though the correlation between crossover frequency and distance from the centromeres is low (R(2) = 0.21). Most of the centromeric regions were low in recombination. The crossover frequency for the entire soybean genome was 7.2%, with extremes much higher and lower than average. The number of recombination hotspots varied from 1 to 12 per chromosome. A high correlation of 0.83 between the distribution of SSR markers and genes suggested close association of SSRs with genes. The knowledge of distribution of recombination on chromosomes may be applied in characterizing and targeting genes.

Next Generation Mapping of Enological Traits in an F2 Interspecific Grapevine Hybrid Family

PubMed Central

Sun, Qi; Manns, David C.; Sacks, Gavin L.; Mansfield, Anna Katharine; Luby, James J.; Londo, Jason P.; Reisch, Bruce I.; Cadle-Davidson, Lance E.; Fennell, Anne Y.

2016-01-01

In winegrapes (Vitis spp.), fruit quality traits such as berry color, total soluble solids content (SS), malic acid content (MA), and yeast assimilable nitrogen (YAN) affect fermentation or wine quality, and are important traits in selecting new hybrid winegrape cultivars. Given the high genetic diversity and heterozygosity of Vitis species and their tendency to exhibit inbreeding depression, linkage map construction and quantitative trait locus (QTL) mapping has relied on F1 families with the use of simple sequence repeat (SSR) and other markers. This study presents the construction of a genetic map by single nucleotide polymorphisms identified through genotyping-by-sequencing (GBS) technology in an F2 mapping family of 424 progeny derived from a cross between the wild species V. riparia Michx. and the interspecific hybrid winegrape cultivar, ‘Seyval’. The resulting map has 1449 markers spanning 2424 cM in genetic length across 19 linkage groups, covering 95% of the genome with an average distance between markers of 1.67 cM. Compared to an SSR map previously developed for this F2 family, these results represent an improved map covering a greater portion of the genome with higher marker density. The accuracy of the map was validated using the well-studied trait berry color. QTL affecting YAN, MA and SS related traits were detected. A joint MA and SS QTL spans a region with candidate genes involved in the malate metabolism pathway. We present an analytical pipeline for calling intercross GBS markers and a high-density linkage map for a large F2 family of the highly heterozygous Vitis genus. This study serves as a model for further genetic investigations of the molecular basis of additional unique characters of North American hybrid wine cultivars and to enhance the breeding process by marker-assisted selection. The GBS protocols for identifying intercross markers developed in this study can be adapted for other heterozygous species. PMID:26974672

Prognostic relevance of microvessel density in colorectal tumours.

PubMed

Abdalla, S A; Behzad, F; Bsharah, S; Kumar, S; Amini, S K; O'Dwyer, S T; Haboubi, N Y

1999-01-01

The importance of angiogenesis as a prognostic marker has been examined in 111 colorectal cancer patients with a minimum follow-up of 5 years. Tumour sections were immunostained with pan-endothelial antibody to CD31. Microvessels were identified and counted in 5 separate areas of highest vascularity (). Analysis of the data showed that the survival was not significantly affected by tumour site, size, grade, patients' age or gender. However, a statistically significant correlation was found between microvessel density (MVD) and survival: patients with an increased number of microvessels survived longer than those with a low number of microvessels (p=0.0007). Therefore, paradoxically, unlike other tumour types, in colorectal cancer MVD appears to be an indicator of good prognosis. The reasons that MVD correlates with good or poor prognosis are likely to vary in different tumours. For instance a frequent difficult issue in colon cancer is the presence of ulceration and adjacent severe inflammation which by itself can increase vascularity. Furthermore, overall prognosis will also depend on other factors, such as oncogenes, extracellular matrix components, adhesion molecules, growth factors, degree of apoptosis and the mode of metastatic spread.

The inhibition of RANK-ligand in the management of postmenopausal osteoporosis and related fractures: the role of denosumab.

PubMed

Capozzi, Anna; Lello, Stefano; Pontecorvi, Alfredo

2014-06-01

There is great interest in new treatments of osteoporosis owing to general ageing of population and increased risk for fragility fractures in the elderly. Current therapies show a good efficacy in improving bone quality and bone density, but, in spite of a certain reduction in fracture rate, according to each treatment, the problem of osteoporotic fractures is yet far from to be solved. Moreover, some treatments may produce different side effects. Denosumab (Dmab), a receptor activator of nuclear factor kappa-B ligand (RANKL)-inhibitor, is an agent recently introduced in clinical practice for treatment of osteoporosis of postmenopausal women. Dmab has improved bone mineral density and prevented new vertebral and non-vertebral fractures with a similar efficacy in comparison with alendronate. Many clinical studies showed Dmab produces also significant improvement versus placebo in bone quality as indicated by decreasing markers of bone turnover. Patients using Dmab reported less risk of AFF (Atypical Femoral Fractures) and ONJ (Osteonecrosis of the Jaw) with an increased number of cellulitis. Here, we review articles using Dmab for female post-menopausal osteoporosis.

Impact of a Dietary Supplement Containing 1,3-Dimethylamylamine on Blood Pressure and Bloodborne Markers of Health: a 10-Week Intervention Study

PubMed Central

Whitehead, Paul N.; Schilling, Brian K.; Farney, Tyler M.; Bloomer, Richard J.

2012-01-01

Background: 1,3-dimethylamylamine is a commonly used ingredient within dietary supplements. Our prior work with this agent indicates a transient increase in blood pressure (systolic in particular) following oral ingestion of a single dosage, but no significant increase in resting blood pressure following chronic ingestion. Moreover, intervention studies involving both two and eight weeks of treatment with finished products containing 1,3-dimethylamylamine indicate minimal or no change in bloodborne markers of health. The present study sought to extend these findings by using a 10-week intervention trial to determine the change in selected markers of health in a sample of men. Methods: 25 healthy men were randomly assigned to either a placebo (n = 13) or to a supplement containing 1,3-dimethylamylamine (n = 12) for a period of 10 weeks. Before and after the intervention, resting blood pressure and heart rate were measured, and blood samples were collected for determination of complete blood count, metabolic panel, and lipid panel. Results: No significant differences were noted between conditions for blood pressure (P > 0.05), although systolic blood pressure increased approximately 6 mmHg with the supplement (diastolic blood pressure decreased approximately 4 mmHg). A main effect for time was noted for heart rate (P = 0.016), with values decreasing from pre to post intervention. There were significant main effects for time for creatinine (increased from pre to post intervention; P = 0.043) and alkaline phosphatase (decreased from pre to post intervention; P = 0.009), with no condition differences noted (P > 0.05). There was a significant interaction noted for low density lipoprotein cholesterol (LDL-C) (P = 0.043), with values decreasing in the supplement group from pre to post intervention approximately 7 mg · dL−1 (P = 0.034). No other effects of significance were noted for bloodborne variables. Conclusion: These data indicate that a dietary supplement containing 1,3-dimethylamylamine does not result in a statistically significant increase in resting heart rate or blood pressure (although systolic blood pressure is increased ∼6 mmHg with supplement use). The supplement does not negatively impact bloodborne markers of health. Further study is needed involving a longer intervention period, a larger sample size, and additional measures of health and safety. PMID:23882146

Genetic linkage map and QTL identification for adventitious rooting traits in red gum eucalypts.

PubMed

Sumathi, Murugan; Bachpai, Vijaya Kumar Waman; Mayavel, A; Dasgupta, Modhumita Ghosh; Nagarajan, Binai; Rajasugunasekar, D; Sivakumar, Veerasamy; Yasodha, Ramasamy

2018-05-01

The eucalypt species, Eucalyptus tereticornis and Eucalyptus camaldulensis , show tolerance to drought and salinity conditions, respectively, and are widely cultivated in arid and semiarid regions of tropical countries. In this study, genetic linkage map was developed for interspecific cross E. tereticornis  ×  E. camaldulensis using pseudo-testcross strategy with simple sequence repeats (SSRs), intersimple sequence repeats (ISSRs), and sequence-related amplified polymorphism (SRAP) markers. The consensus genetic map comprised totally 283 markers with 84 SSRs, 94 ISSRs, and 105 SRAP markers on 11 linkage groups spanning 1163.4 cM genetic distance. Blasting the SSR sequences against E. grandis sequences allowed an alignment of 64% and the average ratio of genetic-to-physical distance was 1.7 Mbp/cM, which strengths the evidence that high amount of synteny and colinearity exists among eucalypts genome. Blast searches also revealed that 37% of SSRs had homologies with genes, which could potentially be used in the variety of downstream applications including candidate gene polymorphism. Quantitative trait loci (QTL) analysis for adventitious rooting traits revealed six QTL for rooting percent and root length on five chromosomes with interval and composite interval mapping. All the QTL explained 12.0-14.7% of the phenotypic variance, showing the involvement of major effect QTL on adventitious rooting traits. Increasing the density of markers would facilitate the detection of more number of small-effect QTL and also underpinning the genes involved in rooting process.

Effect of odanacatib on bone turnover markers, bone density and geometry of the spine and hip of ovariectomized monkeys: a head-to-head comparison with alendronate.

PubMed

Williams, Donald S; McCracken, Paul J; Purcell, Mona; Pickarski, Maureen; Mathers, Parker D; Savitz, Alan T; Szumiloski, John; Jayakar, Richa Y; Somayajula, Sangeetha; Krause, Stephen; Brown, Keenan; Winkelmann, Christopher T; Scott, Boyd B; Cook, Lynn; Motzel, Sherri L; Hargreaves, Richard; Evelhoch, Jeffrey L; Cabal, Antonio; Dardzinski, Bernard J; Hangartner, Thomas N; Duong, Le T

2013-10-01

Odanacatib (ODN) is a selective and reversible Cathepsin K (CatK) inhibitor currently being developed as a once weekly treatment for osteoporosis. Here, effects of ODN compared to alendronate (ALN) on bone turnover, DXA-based areal bone mineral density (aBMD), QCT-based volumetric BMD (vBMD) and geometric parameters were studied in ovariectomized (OVX) rhesus monkeys. Treatment was initiated 10 days after ovariectomy and continued for 20 months. The study consisted of four groups: L-ODN (2 mg/kg, daily p.o.), H-ODN (8/4 mg/kg daily p.o.), ALN (15 μg/kg, twice weekly, s.c.), and VEH (vehicle, daily, p.o.). L-ODN and ALN doses were selected to approximate the clinical exposures of the ODN 50-mg and ALN 70-mg once-weekly, respectively. L-ODN and ALN effectively reduced bone resorption markers uNTx and sCTx compared to VEH. There was no additional efficacy with these markers achieved with H-ODN. Conversely, ODN displayed inversely dose-dependent reduction of bone formation markers, sP1NP and sBSAP, and L-ODN reduced formation to a lesser degree than ALN. At month 18 post-OVX, L-ODN showed robust increases in lumbar spine aBMD (11.4%, p<0.001), spine trabecular vBMD (13.7%, p<0.001), femoral neck (FN) integral (int) vBMD (9.0%, p<0.001) and sub-trochanteric proximal femur (SubTrPF) int vBMD, (6.4%, p<0.001) compared to baseline. L-ODN significantly increased FN cortical thickness (Ct.Th) and cortical bone mineral content (Ct.BMC) by 22.5% (p<0.001) and 21.8% (p<0.001), respectively, and SubTrPF Ct.Th and Ct.BMC by 10.9% (p<0.001) and 11.3% (p<0.001) respectively. Compared to ALN, L-ODN significantly increased FN Ct. BMC by 8.7% (p<0.05), and SubTrPF Ct.Th by 7.6% (p<0.05) and Ct.BMC by 6.2% (p<0.05). H-ODN showed no additional efficacy compared to L-ODN in OVX-monkeys in prevention mode. Taken together, the results from this study have demonstrated that administration of ODN at levels which approximate clinical exposure in OVX-monkeys had comparable efficacy to ALN in DXA-based aBMD and QCT-based vBMD. However, FN cortical mineral content clearly demonstrated superior efficacy of ODN versus ALN in this model of estrogen-deficient non-human primates. © 2013 Elsevier Inc. All rights reserved.

Genetic map of Triticum turgidum based on a hexaploid wheat population without genetic recombination for D genome.

PubMed

Zhang, Li; Luo, Jiang-Tao; Hao, Ming; Zhang, Lian-Quan; Yuan, Zhong-Wei; Yan, Ze-Hong; Liu, Ya-Xi; Zhang, Bo; Liu, Bao-Long; Liu, Chun-Ji; Zhang, Huai-Gang; Zheng, You-Liang; Liu, Deng-Cai

2012-08-13

A synthetic doubled-haploid hexaploid wheat population, SynDH1, derived from the spontaneous chromosome doubling of triploid F1 hybrid plants obtained from the cross of hybrids Triticum turgidum ssp. durum line Langdon (LDN) and ssp. turgidum line AS313, with Aegilops tauschii ssp. tauschii accession AS60, was previously constructed. SynDH1 is a tetraploidization-hexaploid doubled haploid (DH) population because it contains recombinant A and B chromosomes from two different T. turgidum genotypes, while all the D chromosomes from Ae. tauschii are homogenous across the whole population. This paper reports the construction of a genetic map using this population. Of the 606 markers used to assemble the genetic map, 588 (97%) were assigned to linkage groups. These included 513 Diversity Arrays Technology (DArT) markers, 72 simple sequence repeat (SSR), one insertion site-based polymorphism (ISBP), and two high-molecular-weight glutenin subunit (HMW-GS) markers. These markers were assigned to the 14 chromosomes, covering 2048.79 cM, with a mean distance of 3.48 cM between adjacent markers. This map showed good coverage of the A and B genome chromosomes, apart from 3A, 5A, 6A, and 4B. Compared with previously reported maps, most shared markers showed highly consistent orders. This map was successfully used to identify five quantitative trait loci (QTL), including two for spikelet number on chromosomes 7A and 5B, two for spike length on 7A and 3B, and one for 1000-grain weight on 4B. However, differences in crossability QTL between the two T. turgidum parents may explain the segregation distortion regions on chromosomes 1A, 3B, and 6B. A genetic map of T. turgidum including 588 markers was constructed using a synthetic doubled haploid (SynDH) hexaploid wheat population. Five QTLs for three agronomic traits were identified from this population. However, more markers are needed to increase the density and resolution of this map in the future study.

Epicardial Adipose Tissue in the General Middle-aged Population and Its Association With Metabolic Syndrome.

PubMed

Calabuig, Álvaro; Barba, Joaquín; Guembe, María Jesús; Díez, Javier; Berjón, Jesús; Martínez-Vila, Eduardo; Irimia, Pablo; Toledo, Estefanía

2017-04-01

There is currently increasing interest in epicardial adipose tissue (EAT) as a marker of cardiovascular disease. Our purpose was to describe EAT, measured by transthoracic echocardiography, and to assess its association with metabolic syndrome (MS) in the RIVANA population-based study. Physical examination was performed in 880 participants aged 45 to 74 years (492 of them with MS according to the harmonized definition). Fasting glucose, high-density lipoprotein cholesterol, triglyceride, and C-reactive protein concentrations were determined in a blood sample. In all participants, EAT thickness was measured with transthoracic echocardiography at end-systole. Among participants without MS, the prevalence of EAT ≥ 5mm significantly increased with age (OR > 65 years vs 45-54 years=8.22; 95%CI, 3.90-17.35; P for trend<.001). Increasing EAT quintiles were significantly associated with MS (OR fifth quintile vs first quintile=3.26; 95%CI, 1.59-6.71; P for trend=.001). Considering the different MS criteria, increasing quintiles of EAT were independently associated with low high-density lipoprotein cholesterol (OR fifth quintile vs first quintile=2.65; 95%CI, 1.16-6.05; P for trend=.028), high triglycerides (OR fifth quintile vs first quintile=2.22; 95%CI, 1.26-3.90; P for trend=.003), and elevated waist circumference (OR fifth quintile vs first quintile=6.85; 95%CI, 2.91-16.11; P for trend<.001). In a subsample of the general population, EAT measured by echocardiography increased significantly and independently with age. Increased EAT thickness was independently associated with MS and with low high-density lipoprotein cholesterol, high triglycerides, and elevated waist circumference as individual criteria. Copyright © 2016. Published by Elsevier España, S.L.U.

Evidence for Chronic Low-Grade Systemic Inflammation in Individuals with Agoraphobia from a Population-Based Prospective Study

PubMed Central

Wagner, En-Young N.; Wagner, Jan T.; Glaus, Jennifer; Vandeleur, Caroline L.; Castelao, Enrique; Strippoli, Marie-Pierre F.; Vollenweider, Peter; Preisig, Martin; von Känel, Roland

2015-01-01

Background Anxiety disorders have been linked to an increased risk of incident coronary heart disease in which inflammation plays a key pathogenic role. To date, no studies have looked at the association between proinflammatory markers and agoraphobia. Methods In a random Swiss population sample of 2890 persons (35-67 years, 53% women), we diagnosed a total of 124 individuals (4.3%) with agoraphobia using a validated semi-structured psychiatric interview. We also assessed socioeconomic status, traditional cardiovascular risk factors (i.e., body mass index, hypertension, blood glucose levels, total cholesterol/high-density lipoprotein-cholesterol ratio), and health behaviors (i.e., smoking, alcohol consumption, and physical activity), and other major psychiatric diseases (other anxiety disorders, major depressive disorder, drug dependence) which were treated as covariates in linear regression models. Circulating levels of inflammatory markers, statistically controlled for the baseline demographic and health-related measures, were determined at a mean follow-up of 5.5 ± 0.4 years (range 4.7 – 8.5). Results Individuals with agoraphobia had significantly higher follow-up levels of C-reactive protein (p = 0.007) and tumor-necrosis-factor-α (p = 0.042) as well as lower levels of the cardioprotective marker adiponectin (p = 0.032) than their non-agoraphobic counterparts. Follow-up levels of interleukin (IL)-1β and IL-6 did not significantly differ between the two groups. Conclusions Our results suggest an increase in chronic low-grade inflammation in agoraphobia over time. Such a mechanism might link agoraphobia with an increased risk of atherosclerosis and coronary heart disease, and needs to be tested in longitudinal studies. PMID:25875094

Current and Future Methods for Measuring Breast Density: A Brief Comparative Review

PubMed Central

Sak, Mark A.; Littrup, Peter J.; Duric, Neb; Mullooly, Maeve; Sherman, Mark E.; Gierach, Gretchen L.

2017-01-01

Breast density is one of the strongest predictors of breast cancer risk. Women with the densest breasts are 4 to 6 times more likely to develop cancer compared with those with the lowest densities. Breast density is generally assessed using mammographic imaging; however, this approach has limitations. Magnetic resonance imaging and ultrasound tomography are some alternative imaging modalities that can aid mammography in patient screening and the measurement of breast density. As breast density becomes more commonly discussed, knowledge of the advantages and limitations of breast density as a marker of risk will become more critical. This review article discusses the relationship between breast density and breast cancer risk, lists the benefits and drawbacks of using multiple different imaging modalities to measure density and briefly discusses how breast density will be applied to aid in breast cancer prevention and treatment. PMID:28943893

Dietary verbascoside supplementation in donkeys: effects on milk fatty acid profile during lactation, and serum biochemical parameters and oxidative markers.

PubMed

D'Alessandro, A G; Vizzarri, F; Palazzo, M; Martemucci, G

2017-09-01

Various uses of donkeys' milk have been recently proposed for human consumption on the basis of its nutritional characteristics. Improvements in milk fatty acid profile and animal oxidative status can be induced through dietary supplementation of phenolic compounds. The study aimed to evaluate in donkeys the effects of dietary supplementation with verbascoside (VB) on: (i) the fatty acid profile and vitamins A and E contents of milk during a whole lactation, and (ii) blood biochemical parameters and markers of oxidative status of the animals. At foaling, 12 lactating jennies were subdivided into two groups (n 6): control, without VB supplement; VB, receiving a lipid-encapsulated VB supplement. Gross composition, fatty acid profile and vitamins A and E contents in milk were assessed monthly over the 6 months of lactation. Serum total cholesterol, high-density lipoproteins cholesterol and low-density lipoproteins cholesterol, tryglicerides, non-esterified fatty acid, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase, reactive oxygen metabolites, thiobarbituric acid reactive substances (TBARs), vitamin A and vitamin E were evaluated at 8 days after foaling (D0) and then at D90, D105 and D120 of lactation. In milk, the VB supplementation decreased the saturated fatty acids (P<0.05) and increased the monounsaturated fatty acids (P<0.05), and vitamins A and E (P<0.01) values. On the serum parameters, the VB supplementation decreased total cholesterol (P<0.01), tryglicerides, bilirubin, ALT and TBARs, and increased (P<0.01) vitamin E. In conclusion, the VB dietary supplementation affects the nutritional quality of donkey's milk with a benefit on the oxidative status and serum lipidic profile of the animals.

Phenotypic Spectrum in Osteogenesis Imperfecta Due to Mutations in TMEM38B: Unraveling a Complex Cellular Defect.

PubMed

Webb, Emma A; Balasubramanian, Meena; Fratzl-Zelman, Nadja; Cabral, Wayne A; Titheradge, Hannah; Alsaedi, Atif; Saraff, Vrinda; Vogt, Julie; Cole, Trevor; Stewart, Susan; Crabtree, Nicola J; Sargent, Brandi M; Gamsjaeger, Sonja; Paschalis, Eleftherios P; Roschger, Paul; Klaushofer, Klaus; Shaw, Nick J; Marini, Joan C; Högler, Wolfgang

2017-06-01

Recessive mutations in TMEM38B cause type XIV osteogenesis imperfecta (OI) by dysregulating intracellular calcium flux. Clinical and bone material phenotype description and osteoblast differentiation studies. Natural history study in pediatric research centers. Eight patients with type XIV OI. Clinical examinations included bone mineral density, radiographs, echocardiography, and muscle biopsy. Bone biopsy samples (n = 3) were analyzed using histomorphometry, quantitative backscattered electron microscopy, and Raman microspectroscopy. Cellular differentiation studies were performed on proband and control osteoblasts and normal murine osteoclasts. Type XIV OI clinical phenotype ranges from asymptomatic to severe. Previously unreported features include vertebral fractures, periosteal cloaking, coxa vara, and extraskeletal features (muscular hypotonia, cardiac abnormalities). Proband lumbar spine bone density z score was reduced [median -3.3 (range -4.77 to +0.1; n = 7)] and increased by +1.7 (1.17 to 3.0; n = 3) following bisphosphonate therapy. TMEM38B mutant bone has reduced trabecular bone volume, osteoblast, and particularly osteoclast numbers, with >80% reduction in bone resorption. Bone matrix mineralization is normal and nanoporosity low. We demonstrate a complex osteoblast differentiation defect with decreased expression of early markers and increased expression of late and mineralization-related markers. Predominance of trimeric intracellular cation channel type B over type A expression in murine osteoclasts supports an intrinsic osteoclast defect underlying low bone turnover. OI type XIV has a bone histology, matrix mineralization, and osteoblast differentiation pattern that is distinct from OI with collagen defects. Probands are responsive to bisphosphonates and some show muscular and cardiovascular features possibly related to intracellular calcium flux abnormalities. Copyright © 2017 Endocrine Society

The effect of cinnamon extract and long-term aerobic training on heart function, biochemical alterations and lipid profile following exhaustive exercise in male rats.

PubMed

Badalzadeh, Reza; Shaghaghi, Mehrnoush; Mohammadi, Mustafa; Dehghan, Gholamreza; Mohammadi, Zeynab

2014-12-01

Regular training is suggested to offer a host of benefits especially on cardiovascular system. In addition, medicinal plants can attenuate oxidative stress-mediated damages induced by stressor insults. In this study, we investigated the concomitant effect of cinnamon extract and long-term aerobic training on cardiac function, biochemical alterations and lipid profile following exhaustive exercise. Male Wistar rats (250-300 g) were divided into five groups depending on receiving regular training, cinnamon bark extraction, none or both of them, and then encountered with an exhausted exercise in last session. An 8-week endurance training program was designed with a progressive increase in training speed and time. Myocardial hemodynamics was monitored using a balloon-tipped catheter inserted into left ventricles. Blood samples were collected for analyzing biochemical markers, lipid profiles and lipid-peroxidation marker, malondealdehyde (MDA). Trained animals showed an enhanced cardiac force and contractility similar to cinnamon-treated rats. Co-application of regular training and cinnamon had additive effect in cardiac hemodynamic (P<0.05). Both regular training and supplementation with cinnamon significantly decreased serum levels of total cholesterol, low-density lipoprotein (LDL), and increased high-density lipoprotein (HDL) level and HDL/LDL ratio as compared to control group (P<0.01). Furthermore, pre-treatment with cinnamon extract and/or regular training significantly reduced MDA level elevation induced by exhausted exercise (P<0.01). Long-term treatment of rats with cinnamon and regular training improved cardiac hemodynamic through an additive effect. The positive effects of cinnamon and regular training on cardiac function were associated with a reduced serum MDA level and an improved blood lipid profile.