Establishment of apoptotic regulatory network for genetic markers of colorectal cancer.

PubMed

Hao, Yibin; Shan, Guoyong; Nan, Kejun

2017-03-01

Our purpose is to screen out genetic markers applicable to early diagnosis for colorectal cancer and to establish apoptotic regulatory network model for colorectal cancer, thereby providing theoretical evidence and targeted therapy for early diagnosis of colorectal cancer. Taking databases including CNKI, VIP, Wanfang data, Pub Med, and MEDLINE as main sources of literature retrieval, literatures associated with genetic markers applied to early diagnosis of colorectal cancer were searched to perform comprehensive and quantitative analysis by Meta analysis, hence screening genetic markers used in early diagnosis of colorectal cancer. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were employed to establish apoptotic regulatory network model based on screened genetic markers, and then verification experiment was conducted. Through Meta analysis, seven genetic markers were screened out, including WWOX, K-ras, COX-2, p53, APC, DCC and PTEN, among which DCC shows highest diagnostic efficiency. GO analysis of genetic markers found that six genetic markers played role in biological process, molecular function and cellular component. It was indicated in apoptotic regulatory network built by KEGG analysis and verification experiment that WWOX could promote tumor cell apoptotic in colorectal cancer and elevate expression level of p53. The apoptotic regulatory model of colorectal cancer established in this study provides clinically theoretical evidence and targeted therapy for early diagnosis of colorectal cancer.

Genetics of recurrent early-onset major depression (GenRED): significant linkage on chromosome 15q25-q26 after fine mapping with single nucleotide polymorphism markers.

PubMed

Levinson, Douglas F; Evgrafov, Oleg V; Knowles, James A; Potash, James B; Weissman, Myrna M; Scheftner, William A; Depaulo, J Raymond; Crowe, Raymond R; Murphy-Eberenz, Kathleen; Marta, Diana H; McInnis, Melvin G; Adams, Philip; Gladis, Madeline; Miller, Erin B; Thomas, Jo; Holmans, Peter

2007-02-01

The authors studied a dense map of single nucleotide polymorphism (SNP) DNA markers on chromosome 15q25-q26 to maximize the informativeness of genetic linkage analyses in a region where they previously reported suggestive evidence for linkage of recurrent early-onset major depressive disorder. In 631 European-ancestry families with multiple cases of recurrent early-onset major depressive disorder, 88 SNPs were genotyped, and multipoint allele-sharing linkage analyses were carried out. Marker-marker linkage disequilibrium was minimized, and a simulation study with founder haplotypes from these families suggested that linkage scores were not inflated by linkage disequilibrium. The dense SNP map increased the information content of the analysis from around 0.7 to over 0.9. The maximum evidence for linkage was the Z likelihood ratio score statistic of Kong and Cox (Z(LR))=4.69 at 109.8 cM. The exact p value was below the genomewide significance threshold. By contrast, in the genome scan with microsatellite markers at 9 cM spacing, the maximum Z(LR) for European-ancestry families was 3.43 (106.53 cM). It was estimated that the linked locus or loci in this region might account for a 20% or less populationwide increase in risk to siblings of cases. This region has produced modestly positive evidence for linkage to depression and related traits in other studies. These results suggest that DNA sequence variations in one or more genes in the 15q25-q26 region can increase susceptibility to major depression and that efforts are warranted to identify these genes.

Frameworking memory and serotonergic markers.

PubMed

Meneses, Alfredo

2017-07-26

The evidence for neural markers and memory is continuously being revised, and as evidence continues to accumulate, herein, we frame earlier and new evidence. Hence, in this work, the aim is to provide an appropriate conceptual framework of serotonergic markers associated with neural activity and memory. Serotonin (5-hydroxytryptamine [5-HT]) has multiple pharmacological tools, well-characterized downstream signaling in mammals' species, and established 5-HT neural markers showing new insights about memory functions and dysfunctions, including receptors (5-HT1A/1B/1D, 5-HT2A/2B/2C, and 5-HT3-7), transporter (serotonin transporter [SERT]) and volume transmission present in brain areas involved in memory. Bidirectional influence occurs between 5-HT markers and memory/amnesia. A growing number of researchers report that memory, amnesia, or forgetting modifies neural markers. Diverse approaches support the translatability of using neural markers and cerebral functions/dysfunctions, including memory formation and amnesia. At least, 5-HT1A, 5-HT4, 5-HT6, and 5-HT7 receptors and SERT seem to be useful neural markers and therapeutic targets. Hence, several mechanisms cooperate to achieve synaptic plasticity or memory, including changes in the expression of neurotransmitter receptors and transporters.

X linked neonatal centronuclear/myotubular myopathy: evidence for linkage to Xq28 DNA marker loci.

PubMed

Thomas, N S; Williams, H; Cole, G; Roberts, K; Clarke, A; Liechti-Gallati, S; Braga, S; Gerber, A; Meier, C; Moser, H

1990-05-01

We have studied the inheritance of several polymorphic Xq27/28 DNA marker loci in two three generation families with the X linked neonatal lethal form of centronuclear/myotubular myopathy (XL MTM). We found complete linkage of XLMTM to all four informative Xq28 markers analysed, with GCP/RCP (Z = 3.876, theta = 0.00), with DXS15 (Z = 3.737, theta = 0.00), with DXS52 (Z = 2.709, theta = 0.00), and with F8C (Z = 1.020, theta = 0.00). In the absence of any observable recombination, we are unable to sublocalise the XLMTM locus further within the Xq28 region. This evidence for an Xq28 localisation may allow us to carry out useful genetic counselling within such families.

Biological markers of intermediate outcomes in studies of indoor air and other complex mixtures.

PubMed Central

Wilcosky, T C

1993-01-01

Biological markers of intermediate health outcomes sometimes provide a superior alternative to traditional measures of pollutant-related disease. Some opportunities and methodologic issues associated with using markers are discussed in the context of exposures to four complex mixtures: environmental tobacco smoke and nitrogen dioxide, acid aerosols and oxidant outdoor pollution, environmental tobacco smoke and radon, and volatile organic compounds. For markers of intermediate health outcomes, the most important property is the positive predictive value for clinical outcomes of interest. Unless the marker has a known relationship with disease, a marker response conveys no information about disease risk. Most markers are nonspecific in that various exposures cause the same marker response. Although nonspecificity can be an asset in studies of complex mixtures, it leads to problems with confounding and dilution of exposure-response associations in the presence of other exposures. The timing of a marker's measurement in relation to the occurrence of exposure influences the ability to detect a response; measurements made too early or too late may underestimate the response's magnitude. Noninvasive markers, such as those measured in urine, blood, or nasal lavage fluid, are generally more useful for field studies than are invasive markers. However, invasive markers, such as those measured in bronchoalveolar lavage fluid or lung specimens from autopsies, provide the most direct evidence of pulmonary damage from exposure to air pollutants. Unfortunately, the lack of basic information about marker properties (e.g., sensitivity, variability, statistical link with disease) currently precludes the effective use of most markers in studies of complex mixtures. PMID:8206030

Reporting recommendations for tumor marker prognostic studies (REMARK): explanation and elaboration

PubMed Central

2012-01-01

Background The Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) checklist consists of 20 items to report for published tumor marker prognostic studies. It was developed to address widespread deficiencies in the reporting of such studies. In this paper we expand on the REMARK checklist to enhance its use and effectiveness through better understanding of the intent of each item and why the information is important to report. Methods REMARK recommends including a transparent and full description of research goals and hypotheses, subject selection, specimen and assay considerations, marker measurement methods, statistical design and analysis, and study results. Each checklist item is explained and accompanied by published examples of good reporting, and relevant empirical evidence of the quality of reporting. We give prominence to discussion of the 'REMARK profile', a suggested tabular format for summarizing key study details. Summary The paper provides a comprehensive overview to educate on good reporting and provide a valuable reference for the many issues to consider when designing, conducting, and analyzing tumor marker studies and prognostic studies in medicine in general. To encourage dissemination of the Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK): Explanation and Elaboration, this article has also been published in PLoS Medicine. PMID:22642691

Insight into novel biomarkers in penile cancer: Redefining the present and future treatment paradigm?

PubMed

Zargar-Shoshtari, Kamran; Sharma, Pranav; Spiess, Philippe E

2017-11-02

Biomarkers are increasingly used in the diagnosis and management of various malignancies. Selected biomarkers may also play a role in management of certain cases of penile carcinoma. In this article, we provide an overview of the clinical role of such markers in the management of penile cancer. This is a nonsystematic review of relevant literature assessing biomarkers in penile carcinoma. Evidence of infections with human papillomavirus and its surrogate markers may have important prognostic value in patients with localized or metastatic penile cancer. Squamous cell carcinoma antigen, p53, C-reactive protein, Ki-67, proliferating cell nuclear antigen, cyclin D1, as well as other markers have been studied with various degree of evidence in support of clinical utility in penile cancer. No single marker may have all the answers, and future research should focus on genomic analysis of individual penile tumors, attempting to identify specific targets for treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Brain structural, neurochemical and neuroinflammatory markers of psychosis onset and relapse: Is there evidence for a psychosis relapse signature?

PubMed

Cropley, Vanessa; Wood, Stephen J; Pantelis, Christos

2013-05-10

Schizophrenia is a debilitating illness that is often associated with progressive clinical deterioration following repeated episodes of illness. Despite the clinical evidence for clinical attrition, the nature of any associated neurobiological pathology has not been examined systematically. This review examines the neurobiological imaging markers associated with psychosis onset and relapse and considers whether these may be potential state markers of acute psychosis. We report several markers of neurobiological changes associated with acute psychosis. These include dynamic changes in brain structure in the frontal and temporal regions, neurochemical alterations in dopamine and glutamate and evidence for neuroinflammation through microglial activation. We propose that with the use of repeat longitudinal assessments of brain imaging markers over the course of a psychosis relapse, the neurobiological trajectory indicative of a 'relapse signature' for psychosis will be identified.

Establishment of apoptotic regulatory network for genetic markers of colorectal cancer and optimal selection of traditional Chinese medicine target.

PubMed

Tian, Tongde; Chen, Chuanliang; Yang, Feng; Tang, Jingwen; Pei, Junwen; Shi, Bian; Zhang, Ning; Zhang, Jianhua

2017-03-01

The paper aimed to screen out genetic markers applicable to early diagnosis for colorectal cancer and establish apoptotic regulatory network model for colorectal cancer, and to analyze the current situation of traditional Chinese medicine (TCM) target, thereby providing theoretical evidence for early diagnosis and targeted therapy of colorectal cancer. Taking databases including CNKI, VIP, Wanfang data, Pub Med, and MEDLINE as main sources of literature retrieval, literatures associated with genetic markers that are applied to early diagnosis of colorectal cancer were searched and performed comprehensive and quantitative analysis by Meta analysis, hence screening genetic markers used in early diagnosis of colorectal cancer. KEGG analysis was employed to establish apoptotic regulatory network model based on screened genetic markers, and optimization was conducted on TCM targets. Through Meta analysis, seven genetic markers were screened out, including WWOX, K-ras, COX-2, P53, APC, DCC and PTEN, among which DCC has the highest diagnostic efficiency. Apoptotic regulatory network was built by KEGG analysis. Currently, it was reported that TCM has regulatory function on gene locus in apoptotic regulatory network. The apoptotic regulatory model of colorectal cancer established in this study provides theoretical evidence for early diagnosis and TCM targeted therapy of colorectal cancer in clinic.

Associations between dopamine and serotonin genes and job satisfaction: preliminary evidence from the Add Health Study.

PubMed

Song, Zhaoli; Li, Wendong; Arvey, Richard D

2011-11-01

Previous behavioral genetic studies have found that job satisfaction is partially heritable. We went a step further to examine particular genetic markers that may be associated with job satisfaction. Using an oversample from the National Adolescent Longitudinal Study (Add Health Study), we found 2 genetic markers, dopamine receptor gene DRD4 VNTR and serotonin transporter gene 5-HTTLPR, to be weakly but significantly associated with job satisfaction. Furthermore, we found study participants' level of pay to mediate the DRD4 and job satisfaction relationship. However, we found no evidence that self-esteem mediated the relationships between these 2 genes and job satisfaction. The study represents an initial effort to introduce a molecular genetics approach to the fields of organizational psychology and organizational behavior. (c) 2011 APA, all rights reserved.

Epigenetic Biomarkers of Breast Cancer Risk: Across the Breast Cancer Prevention Continuum.

PubMed

Terry, Mary Beth; McDonald, Jasmine A; Wu, Hui Chen; Eng, Sybil; Santella, Regina M

2016-01-01

Epigenetic biomarkers, such as DNA methylation, can increase cancer risk through altering gene expression. The Cancer Genome Atlas (TCGA) Network has demonstrated breast cancer-specific DNA methylation signatures. DNA methylation signatures measured at the time of diagnosis may prove important for treatment options and in predicting disease-free and overall survival (tertiary prevention). DNA methylation measurement in cell free DNA may also be useful in improving early detection by measuring tumor DNA released into the blood (secondary prevention). Most evidence evaluating the use of DNA methylation markers in tertiary and secondary prevention efforts for breast cancer comes from studies that are cross-sectional or retrospective with limited corresponding epidemiologic data, raising concerns about temporality. Few prospective studies exist that are large enough to address whether DNA methylation markers add to the prediction of tertiary and secondary outcomes over and beyond standard clinical measures. Determining the role of epigenetic biomarkers in primary prevention can help in identifying modifiable pathways for targeting interventions and reducing disease incidence. The potential is great for DNA methylation markers to improve cancer outcomes across the prevention continuum. Large, prospective epidemiological studies will provide essential evidence of the overall utility of adding these markers to primary prevention efforts, screening, and clinical care.

Molecular genetic studies of natives on Easter Island: evidence of an early European and Amerindian contribution to the Polynesian gene pool.

PubMed

Lie, B A; Dupuy, B M; Spurkland, A; Fernández-Viña, M A; Hagelberg, E; Thorsby, E

2007-01-01

Most archaeological and linguistic evidence suggest a Polynesian origin of the population of Easter Island (Rapanui), and this view has been supported by the identification of Polynesian mitochondrial DNA (mtDNA) polymorphisms in prehistoric skeletal remains. However, some evidence of an early South American contact also exists (the sweet potato, bottle gourd etc.), but genetic studies have so far failed to show an early Amerindian contribution to the gene pool on Easter Island. To address this issue, we analyzed mtDNA and Y chromosome markers and performed high-resolution human leukocyte antigen (HLA) genotyping of DNA harvested from previously collected sera of 48 reputedly nonadmixed native Easter Islanders. All individuals carried mtDNA types and HLA alleles previously found in Polynesia, and most men carried Y chromosome markers of Polynesian origin, providing further evidence of a Polynesian origin of the population of Easter Island. A few individuals carried HLA alleles and/or Y chromosome markers of European origin. More interestingly, some individuals carried the HLA alleles A*0212 and B*3905, which are of typical Amerindian origin. The genealogy of some of the individuals carrying these non-Polynesian HLA alleles and their haplotypic backgrounds suggest an introduction into Easter Island in the early 1800s, or earlier. Thus, there may have been an early European and Amerindian contribution to the Polynesian gene pool of Easter Island.

Diagnosing Appendicitis: Evidence-Based Review of the Diagnostic Approach in 2014

PubMed Central

Shogilev, Daniel J.; Duus, Nicolaj; Odom, Stephen R.; Shapiro, Nathan I.

2014-01-01

Introduction Acute appendicitis is the most common abdominal emergency requiring emergency surgery. However, the diagnosis is often challenging and the decision to operate, observe or further work-up a patient is often unclear. The utility of clinical scoring systems (namely the Alvarado score), laboratory markers, and the development of novel markers in the diagnosis of appendicitis remains controversial. This article presents an update on the diagnostic approach to appendicitis through an evidence-based review. Methods We performed a broad Medline search of radiological imaging, the Alvarado score, common laboratory markers, and novel markers in patients with suspected appendicitis. Results Computed tomography (CT) is the most accurate mode of imaging for suspected cases of appendicitis, but the associated increase in radiation exposure is problematic. The Alvarado score is a clinical scoring system that is used to predict the likelihood of appendicitis based on signs, symptoms and laboratory data. It can help risk stratify patients with suspected appendicitis and potentially decrease the use of CT imaging in patients with certain Alvarado scores. White blood cell (WBC), C-reactive protein (CRP), granulocyte count and proportion of polymorphonuclear (PMN) cells are frequently elevated in patients with appendicitis, but are insufficient on their own as a diagnostic modality. When multiple markers are used in combination their diagnostic utility is greatly increased. Several novel markers have been proposed to aid in the diagnosis of appendicitis; however, while promising, most are only in the preliminary stages of being studied. Conclusion While CT is the most accurate mode of imaging in suspected appendicitis, the accompanying radiation is a concern. Ultrasound may help in the diagnosis while decreasing the need for CT in certain circumstances. The Alvarado Score has good diagnostic utility at specific cutoff points. Laboratory markers have very limited diagnostic utility on their own but show promise when used in combination. Further studies are warranted for laboratory markers in combination and to validate potential novel markers. PMID:25493136

Variable expression of molecular markers in juvenile nasopharyngeal angiofibroma.

PubMed

Mishra, A; Pandey, A; Mishra, S C

2017-09-01

Molecular categorisation may explain the wide variation in the clinical characteristics of juvenile nasopharyngeal angiofibroma. Variations in molecular markers in juvenile nasopharyngeal angiofibroma in an Indian population were investigated and compared with global reports. Variable molecular marker expression was demonstrated at the regional and global levels. A wide variation in molecular characteristics is evident. Molecular data have been reported for only 11 countries, indicating a clear geographical bias. Only 58 markers have been studied, and most are yet to be validated. Research into the molecular epidemiology of juvenile nasopharyngeal angiofibroma is still in its infancy. Although the molecular variation is not well understood, data obtained so far have prompted important research questions. Hence, multicentre collaborative molecular studies are needed to establish the aetiopathogenesis and establish molecular surrogates for clinical characteristics.

Significant Linkage for Tourette Syndrome in a Large French Canadian Family

PubMed Central

Mérette, Chantal; Brassard, Andrée; Potvin, Anne; Bouvier, Hélène; Rousseau, François; Émond, Claudia; Bissonnette, Luc; Roy, Marc-André; Maziade, Michel; Ott, Jurg; Caron, Chantal

2000-01-01

Family and twin studies provide strong evidence that genetic factors are involved in the transmission of Gilles de la Tourette syndrome (TS) and related psychiatric disorders. To detect the underlying susceptibility gene(s) for TS, we performed linkage analysis in one large French Canadian family (127 members) from the Charlevoix region, in which 20 family members were definitely affected by TS and 20 others showed related tic disorders. Using model-based linkage analysis, we observed a LOD score of 3.24 on chromosome 11 (11q23). This result was obtained in a multipoint approach involving marker D11S1377, the marker for which significant linkage disequilibrium with TS recently has been detected in an Afrikaner population. Altogether, 25 markers were studied, and, for level of significance, we derived a criterion that took into account the multiple testing arising from the use of three phenotype definitions and three modes of inheritance, a procedure that yielded a LOD score of 3.18. Hence, even after adjustment for multiple testing, the present study shows statistically significant evidence for genetic linkage with TS. PMID:10986045

Serum markers of bone turnover change in response to depletion and repletion of fruit and vegetable intake in adults: A 28-wk single-arm experimental feeding intervention

USDA-ARS?s Scientific Manuscript database

Data from controlled intervention trials are lacking to support observational evidence suggesting a positive association between intake of fruit and vegetable (FV) and bone health. The objective of this study was to assess serum markers of bone turnover change in response to FV depletion and repleti...

Vitamin D and inflammatory markers: cross-sectional analyses using data from the English Longitudinal Study of Ageing (ELSA).

PubMed

de Oliveira, Cesar; Biddulph, Jane P; Hirani, Vasant; Schneider, Ione Jayce Ceola

2017-01-01

Recent evidence suggests that low vitamin D concentrations are associated with increased levels of inflammatory markers. However, there are limited studies investigating associations between vitamin D levels and inflammatory markers in the general population and much of this evidence in older adults is inconclusive. Therefore, this study investigates the cross-sectional association of serum 25-hydroxyvitamin D (25(OH)D) levels with inflammatory markers in 5870 older English adults from wave 6 (2012-2013) of the English Longitudinal Study of Ageing (ELSA). ELSA is a large prospective observational study of community-dwelling people aged 50 years and over in England. Serum 25(OH)D levels, C-reactive protein (CRP) levels, plasma fibrinogen levels, white blood cell count (WBC), age, season of blood collection, waist circumference, total non-pension household wealth, measures of health and health behaviours that included depression, number of cardiovascular, non-cardiovascular conditions and difficulties in activities of daily living, smoking, and physical activity were measured. There was a significant negative association between low 25(OH)D levels (≤30 nmol/l) and CRP (OR 1·23, 95 % CI 1·00, 1·51) and WBC (OR 1·35, 95 % CI 1·13, 1·60) that remained after adjustment for a wide range of covariates of clinical significance. However, for fibrinogen, the association did not remain significant when waist circumference was entered in the final model. Our findings showed that 25(OH)D levels were associated with two out the three inflammatory markers investigated. The independent and inverse association between serum 25(OH)D levels and inflammation suggests a potential anti-inflammatory role for vitamin D in older English individuals from the general population.

Bi-parental cytoplasmic DNA inheritance in Wisteria (fabaceae): evidence from a natural experiment

Treesearch

Jennifer L. Trusty; Kataren J. Johnson; Graeme B. Lockaby; Leslie R. Goertzen

2007-01-01

Cytoplasmic inheritance was investigated in interspecific hybrids of Wisteria sinensis and W. floribunda. Species-specific nuclear, mitochondrial and plastid DNA markers were identified from wild-collected plants of each species in its native range. These markers provide evidence for the bi-parental transmission of plastids in...

Genomic signatures among Oncorhynchus nerka ecotypes to inform conservation and management of endangered Sockeye Salmon.

PubMed

Nichols, Krista M; Kozfkay, Christine C; Narum, Shawn R

2016-12-01

Conservation of life history variation is an important consideration for many species with trade-offs in migratory characteristics. Many salmonid species exhibit both resident and migratory strategies that capitalize on benefits in freshwater and marine environments. In this study, we investigated genomic signatures for migratory life history in collections of resident and anadromous Oncorhynchus nerka (Kokanee and Sockeye Salmon, respectively) from two lake systems, using ~2,600 SNPs from restriction-site-associated DNA sequencing (RAD-seq). Differing demographic histories were evident in the two systems where one pair was significantly differentiated (Redfish Lake, F ST  = 0.091 [95% confidence interval: 0.087 to 0.095]) but the other pair was not (Alturas Lake, F ST  = -0.007 [-0.008 to -0.006]). Outlier and association analyses identified several candidate markers in each population pair, but there was limited evidence for parallel signatures of genomic variation associated with migration. Despite lack of evidence for consistent markers associated with migratory life history in this species, candidate markers were mapped to functional genes and provide evidence for adaptive genetic variation within each lake system. Life history variation has been maintained in these nearly extirpated populations of O. nerka, and conservation efforts to preserve this diversity are important for long-term resiliency of this species.

Clinical Applications of Procalcitonin in Pediatrics: An Advanced Biomarker for Inflammation and Infection-Can It Also Be Used in Trauma?

PubMed

Koutroulis, Ioannis; Loscalzo, Steven M; Kratimenos, Panagiotis; Singh, Sabina; Weiner, Evan; Syriopoulou, Vassiliki; Theocharis, Stamatios; Chrousos, Georgios

2014-01-01

Background. Procalcitonin is a small molecular peptide that has gained increased support as an adjunct diagnostic marker of infection in the adult population; the concordant body of evidence for the use of procalcitonin in pediatric populations is far less complete. Objectives. Our objective is to review the current evidence supporting the utilization of procalcitonin in children in a variety of clinical scenarios including SIRS, sepsis, burns, and trauma and to identify existing knowledge gaps. Methods. A thorough review of the literature was performed utilizing PubMed. We focused on using meta-analysis from adult populations to review current practices in interpretation and methodology and find concordant pediatric studies to determine if the same applications are validated in pediatric populations. Results. Current evidence supports the usage of procalcitonin as both a sensitive and a specific marker for the differentiation of systemic inflammatory response syndrome from sepsis in pediatrics with increased diagnostic accuracy compared to commonly used biomarkers including complete blood counts and C-reactive protein. Conclusions. Although the body of evidence is limited, initial observations suggest that procalcitonin can be used in pediatric trauma and burn patients as both a prognostic and a diagnostic marker, aiding in the identification of infection in patients with extensive underlying inflammation.

Clinical Applications of Procalcitonin in Pediatrics: An Advanced Biomarker for Inflammation and Infection—Can It Also Be Used in Trauma?

PubMed Central

Loscalzo, Steven M.; Singh, Sabina; Weiner, Evan; Syriopoulou, Vassiliki; Theocharis, Stamatios; Chrousos, Georgios

2014-01-01

Background. Procalcitonin is a small molecular peptide that has gained increased support as an adjunct diagnostic marker of infection in the adult population; the concordant body of evidence for the use of procalcitonin in pediatric populations is far less complete. Objectives. Our objective is to review the current evidence supporting the utilization of procalcitonin in children in a variety of clinical scenarios including SIRS, sepsis, burns, and trauma and to identify existing knowledge gaps. Methods. A thorough review of the literature was performed utilizing PubMed. We focused on using meta-analysis from adult populations to review current practices in interpretation and methodology and find concordant pediatric studies to determine if the same applications are validated in pediatric populations. Results. Current evidence supports the usage of procalcitonin as both a sensitive and a specific marker for the differentiation of systemic inflammatory response syndrome from sepsis in pediatrics with increased diagnostic accuracy compared to commonly used biomarkers including complete blood counts and C-reactive protein. Conclusions. Although the body of evidence is limited, initial observations suggest that procalcitonin can be used in pediatric trauma and burn patients as both a prognostic and a diagnostic marker, aiding in the identification of infection in patients with extensive underlying inflammation. PMID:27355024

Oxidative stress, oxidative balance score, and hypertension among a racially diverse population.

PubMed

Annor, Francis B; Goodman, Michael; Okosun, Ike S; Wilmot, Douglas W; Il'yasova, Dora; Ndirangu, Murugi; Lakkur, Sindhu

2015-08-01

Hypertension is a risk factor for several vascular diseases. Evidence suggests that oxidative stress (OS) plays a significant role in its pathophysiology. Human studies have shown inconsistent results, varying based on the OS biomarker and study population. In a racially diverse population, examine the association between: (1) blood pressure or hypertension and four markers of OS and (2) blood pressure or hypertension and oxidative balance score (OBS). Using data (n = 317) from the cross-sectional study on race, stress, and hypertension, an OBS was constructed from various measures of pro-oxidant and antioxidant exposures. OS was assessed by four biomarkers: fluorescence oxidative products, F2-isoprostanes, mitochondrial DNA copy number, and gamma tocopherol. Multivariate linear and logistic regression analyses were used to estimate the associations of interest. None of the adjusted associations between hypertension and OS markers was statistically significant. OBS was inversely associated with hypertension after adjusting for study covariates. Persons with higher OBS have lower odds of having hypertension; however, the evidence on the relationship between OS markers and blood pressure remains unconvincing. Copyright © 2015 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Convergent linkage evidence from two Latin-American population isolates supports the presence of a susceptibility locus for bipolar disorder in 5q31-34.

PubMed

Herzberg, Ibi; Jasinska, Anna; García, Jenny; Jawaheer, Damini; Service, Susan; Kremeyer, Barbara; Duque, Constanza; Parra, María V; Vega, Jorge; Ortiz, Daniel; Carvajal, Luis; Polanco, Guadalupe; Restrepo, Gabriel J; López, Carlos; Palacio, Carlos; Levinson, Matthew; Aldana, Ileana; Mathews, Carol; Davanzo, Pablo; Molina, Julio; Fournier, Eduardo; Bejarano, Julio; Ramírez, Magui; Ortiz, Carmen Araya; Araya, Xinia; Sabatti, Chiara; Reus, Victor; Macaya, Gabriel; Bedoya, Gabriel; Ospina, Jorge; Freimer, Nelson; Ruiz-Linares, Andrés

2006-11-01

We performed a whole genome microsatellite marker scan in six multiplex families with bipolar (BP) mood disorder ascertained in Antioquia, a historically isolated population from North West Colombia. These families were characterized clinically using the approach employed in independent ongoing studies of BP in the closely related population of the Central Valley of Costa Rica. The most consistent linkage results from parametric and non-parametric analyses of the Colombian scan involved markers on 5q31-33, a region implicated by the previous studies of BP in Costa Rica. Because of these concordant results, a follow-up study with additional markers was undertaken in an expanded set of Colombian and Costa Rican families; this provided a genome-wide significant evidence of linkage of BPI to a candidate region of approximately 10 cM in 5q31-33 (maximum non-parametric linkage score=4.395, P<0.00004). Interestingly, this region has been implicated in several previous genetic studies of schizophrenia and psychosis, including disease association with variants of the enthoprotin and gamma-aminobutyric acid receptor genes.

Evidence for bivariate linkage of obesity and HDL-C levels in the Framingham Heart Study.

PubMed

Arya, Rector; Lehman, Donna; Hunt, Kelly J; Schneider, Jennifer; Almasy, Laura; Blangero, John; Stern, Michael P; Duggirala, Ravindranath

2003-12-31

Epidemiological studies have indicated that obesity and low high-density lipoprotein (HDL) levels are strong cardiovascular risk factors, and that these traits are inversely correlated. Despite the belief that these traits are correlated in part due to pleiotropy, knowledge on specific genes commonly affecting obesity and dyslipidemia is very limited. To address this issue, we first conducted univariate multipoint linkage analysis for body mass index (BMI) and HDL-C to identify loci influencing variation in these phenotypes using Framingham Heart Study data relating to 1702 subjects distributed across 330 pedigrees. Subsequently, we performed bivariate multipoint linkage analysis to detect common loci influencing covariation between these two traits. We scanned the genome and identified a major locus near marker D6S1009 influencing variation in BMI (LOD = 3.9) using the program SOLAR. We also identified a major locus for HDL-C near marker D2S1334 on chromosome 2 (LOD = 3.5) and another region near marker D6S1009 on chromosome 6 with suggestive evidence for linkage (LOD = 2.7). Since these two phenotypes have been independently mapped to the same region on chromosome 6q, we used the bivariate multipoint linkage approach using SOLAR. The bivariate linkage analysis of BMI and HDL-C implicated the genetic region near marker D6S1009 as harboring a major gene commonly influencing these phenotypes (bivariate LOD = 6.2; LODeq = 5.5) and appears to improve power to map the correlated traits to a region, precisely. We found substantial evidence for a quantitative trait locus with pleiotropic effects, which appears to influence both BMI and HDL-C phenotypes in the Framingham data.

Genetic Confirmation of Mungbean (Vigna radiata) and Mashbean (Vigna mungo) Interspecific Recombinants using Molecular Markers.

PubMed

Abbas, Ghulam; Hameed, Amjad; Rizwan, Muhammad; Ahsan, Muhammad; Asghar, Muhammad J; Iqbal, Nayyer

2015-01-01

Molecular confirmation of interspecific recombinants is essential to overcome the issues like self-pollination, environmental influence, and inadequacy of morphological characteristics during interspecific hybridization. The present study was conducted for genetic confirmation of mungbean (female) and mashbean (male) interspecific crosses using molecular markers. Initially, polymorphic random amplified polymorphic DNA (RAPD), universal rice primers (URP), and simple sequence repeats (SSR) markers differentiating parent genotypes were identified. Recombination in hybrids was confirmed using these polymorphic DNA markers. The NM 2006 × Mash 88 was most successful interspecific cross. Most of true recombinants confirmed by molecular markers were from this cross combination. SSR markers were efficient in detecting genetic variability and recombination with reference to specific chromosomes and particular loci. SSR (RIS) and RAPD identified variability dispersed throughout the genome. In conclusion, DNA based marker assisted selection (MAS) efficiently confirmed the interspecific recombinants. The results provided evidence that MAS can enhance the authenticity of selection in mungbean improvement program.

A pseudoautosomal random amplified polymorphic DNA marker for the sex chromosomes of Silene dioica.

PubMed Central

Di Stilio, V S; Kesseli, R V; Mulcahy, D L

1998-01-01

The segregation pattern of an 810-bp random amplified polymorphic DNA (RAPD) band in the F1 and backcross generations of a Silene dioica (L.) Clairv. family provides evidence that this molecular marker is located in the pseudoautosomal region (PAR) of the X and Y chromosomes. The marker was found through a combination of bulked segregant analysis (BSA) and RAPD techniques. Recombination rates between this pseudoautosomal marker and the differentiating portion of the Y chromosome are 15% in both generations. Alternative explanations involving nondisjunction or autosomal inheritance are presented and discussed. Chromosome counts provide evidence against the nondisjunction hypothesis, and probability calculations argue against the possibility of autosomal inheritance. This constitutes the first report of a pseudoautosomal DNA marker for plant sex chromosomes. PMID:9691057

Evaluation of the impact of genetic linkage in forensic identity and relationship testing for expanded DNA marker sets.

PubMed

Tillmar, Andreas O; Phillips, Chris

2017-01-01

Advances in massively parallel sequencing technology have enabled the combination of a much-expanded number of DNA markers (notably STRs and SNPs in one or combined multiplexes), with the aim of increasing the weight of evidence in forensic casework. However, when data from multiple loci on the same chromosome are used, genetic linkage can affect the final likelihood calculation. In order to study the effect of linkage for different sets of markers we developed the biostatistical tool ILIR, (Impact of Linkage on forensic markers for Identity and Relationship tests). The ILIR tool can be used to study the overall impact of genetic linkage for an arbitrary set of markers used in forensic testing. Application of ILIR can be useful during marker selection and design of new marker panels, as well as being highly relevant for existing marker sets as a way to properly evaluate the effects of linkage on a case-by-case basis. ILIR, implemented via the open source platform R, includes variation and genomic position reference data for over 40 STRs and 140 SNPs, combined with the ability to include additional forensic markers of interest. The use of the software is demonstrated with examples from several different established marker sets (such as the expanded CODIS core loci) including a review of the interpretation of linked genetic data. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Immunohistochemical Markers of Neural Progenitor Cells in the Early Embryonic Human Cerebral Cortex

PubMed Central

Vinci, L.; Ravarino, A.; Fanos, V.; Naccarato, A.G.; Senes, G.; Gerosa, C.; Bevilacqua, G.; Faa, G.; Ambu, R.

2016-01-01

The development of the human central nervous system represents a delicate moment of embryogenesis. The purpose of this study was to analyze the expression of multiple immunohistochemical markers in the stem/progenitor cells in the human cerebral cortex during the early phases of development. To this end, samples from cerebral cortex were obtained from 4 human embryos of 11 weeks of gestation. Each sample was formalin-fixed, paraffin embedded and immunostained with several markers including GFAP, WT1, Nestin, Vimentin, CD117, S100B, Sox2, PAX2, PAX5, Tβ4, Neurofilament, CD44, CD133, Synaptophysin and Cyclin D1. Our study shows the ability of the different immunohistochemical markers to evidence different zones of the developing human cerebral cortex, allowing the identification of the multiple stages of differentiation of neuronal and glial precursors. Three important markers of radial glial cells are evidenced in this early gestational age: Vimentin, Nestin and WT1. Sox2 was expressed by the stem/progenitor cells of the ventricular zone, whereas the postmitotic neurons of the cortical plate were immunostained by PAX2 and NSE. Future studies are needed to test other important stem/progenitor cells markers and to better analyze differences in the immunohistochemical expression of these markers during gestation. PMID:26972711

A candidate gene study in low HDL-cholesterol families provides evidence for the involvement of the APOA2 gene and the APOA1C3A4 gene cluster.

PubMed

Lilja, Heidi E; Soro, Aino; Ylitalo, Kati; Nuotio, Ilpo; Viikari, Jorma S A; Salomaa, Veikko; Vartiainen, Erkki; Taskinen, Marja-Riitta; Peltonen, Leena; Pajukanta, Päivi

2002-09-01

In patients with premature coronary heart disease, the most common lipoprotein abnormality is high-density lipoprotein (HDL) deficiency. To assess the genetic background of the low HDL-cholesterol trait, we performed a candidate gene study in 25 families with low HDL, collected from the genetically isolated population of Finland. We studied 21 genes encoding essential proteins involved in the HDL metabolism by genotyping intragenic and flanking markers for these genes. We found suggestive evidence for linkage in two candidate regions: Marker D1S2844, in the apolipoprotein A-II (APOA2) region, yielded a LOD score of 2.14 and marker D11S939 flanking the apolipoprotein A-I/C-III/A-IV gene cluster (APOA1C3A4) produced a LOD score of 1.69. Interestingly, we identified potential shared haplotypes in these two regions in a subset of low HDL families. These families also contributed to the obtained positive LOD scores, whereas the rest of the families produced negative LOD scores. None of the remaining candidate regions provided any evidence for linkage. Since only a limited number of loci were tested in this candidate gene study, these LOD scores suggest significant involvement of the APOA2 gene and the APOA1C3A4 gene cluster, or loci in their immediate vicinity, in the pathogenesis of low HDL.

Evidence of Avian and Possum Fecal Contamination in Rainwater Tanks as Determined by Microbial Source Tracking Approaches

PubMed Central

Hamilton, K. A.; Gyawali, P.; Toze, S.; Haas, C. N.

2016-01-01

ABSTRACT Avian and possum fecal droppings may negatively impact roof-harvested rainwater (RHRW) water quality due to the presence of zoonotic pathogens. This study was aimed at evaluating the performance characteristics of a possum feces-associated (PSM) marker by screening 210 fecal and wastewater samples from possums (n = 20) and a range of nonpossum hosts (n = 190) in Southeast Queensland, Australia. The host sensitivity and specificity of the PSM marker were 0.90 and 0.95 (maximum value, 1.00), respectively. The mean concentrations of the GFD marker in possum fecal DNA samples (8.8 × 107 gene copies per g of feces) were two orders of magnitude higher than those in the nonpossum fecal DNA samples (5.0 × 105 gene copies per g of feces). The host sensitivity, specificity, and concentrations of the avian feces-associated GFD marker were reported in our recent study (W. Ahmed, V. J. Harwood, K. Nguyen, S. Young, K. Hamilton, and S. Toze, Water Res 88:613–622, 2016, http://dx.doi.org/10.1016/j.watres.2015.10.050). The utility of the GFD and PSM markers was evaluated by testing a large number of tank water samples (n = 134) from the Brisbane and Currumbin areas. GFD and PSM markers were detected in 39 of 134 (29%) and 11 of 134 (8%) tank water samples, respectively. The GFD marker concentrations in PCR-positive samples ranged from 3.7 × 102 to 8.5 × 105 gene copies per liter, whereas the concentrations of the PSM marker ranged from 2.0 × 103 to 6.8 × 103 gene copies per liter of water. The results of this study suggest the presence of fecal contamination in tank water samples from avian and possum hosts. This study has established an association between the degradation of microbial tank water quality and avian and possum feces. Based on the results, we recommend disinfection of tank water, especially for tanks designated for potable use. IMPORTANCE The use of roof-harvested rainwater (RHRW) for domestic purposes is a globally accepted practice. The presence of pathogens in rainwater tanks has been reported by several studies, supporting the necessity for the management of potential health risks. The sources of fecal pollution in rainwater tanks are unknown. However, the application of microbial source tracking (MST) markers has the potential to identify the sources of fecal contamination in a rainwater tank. In this study, we provide evidence of avian and possum fecal contamination in tank water samples using molecular markers. This study established a potential link between the degradation of the microbial quality of tank water and avian and possum feces. PMID:27208100

Synteny between the Pro/sup +/ marker and human glutamate oxaloacetate transaminase

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

Jones, C.

1975-01-01

Chinese hamster ovary cells with a specific auxotrophy for proline were fused with human cells from a variety of sources and the resulting hybrids analyzed for human genetic markers. Of 63 hybrid clones examined, 27 possessed both proline and cytoplasmic glutamate oxaloacetate transaminase markers; 36 had neither; and no clones were found possessing one and not the other. These results constitute evidence that the proline and glutamate oxaloacetate transaminase markers are syntenic. Evidence for absence of synteny between these and a variety of other human genes is presented. Biochemical tracer experiments established that the proline biosynthetic pathway through glutamate hasmore » been restored in the Pro/sup +/ hybrids.« less

Temporal Expression of Peripheral Blood Leukocyte Biomarkers in a Macaca fascicularis Infection Model of Tuberculosis; Comparison with Human Datasets and Analysis with Parametric/Non-parametric Tools for Improved Diagnostic Biomarker Identification

PubMed Central

Wareham, Alice; Lewandowski, Kuiama S.; Williams, Ann; Dennis, Michael J.; Sharpe, Sally; Vipond, Richard; Silman, Nigel; Ball, Graham

2016-01-01

A temporal study of gene expression in peripheral blood leukocytes (PBLs) from a Mycobacterium tuberculosis primary, pulmonary challenge model Macaca fascicularis has been conducted. PBL samples were taken prior to challenge and at one, two, four and six weeks post-challenge and labelled, purified RNAs hybridised to Operon Human Genome AROS V4.0 slides. Data analyses revealed a large number of differentially regulated gene entities, which exhibited temporal profiles of expression across the time course study. Further data refinements identified groups of key markers showing group-specific expression patterns, with a substantial reprogramming event evident at the four to six week interval. Selected statistically-significant gene entities from this study and other immune and apoptotic markers were validated using qPCR, which confirmed many of the results obtained using microarray hybridisation. These showed evidence of a step-change in gene expression from an ‘early’ FOS-associated response, to a ‘late’ predominantly type I interferon-driven response, with coincident reduction of expression of other markers. Loss of T-cell-associate marker expression was observed in responsive animals, with concordant elevation of markers which may be associated with a myeloid suppressor cell phenotype e.g. CD163. The animals in the study were of different lineages and these Chinese and Mauritian cynomolgous macaque lines showed clear evidence of differing susceptibilities to Tuberculosis challenge. We determined a number of key differences in response profiles between the groups, particularly in expression of T-cell and apoptotic makers, amongst others. These have provided interesting insights into innate susceptibility related to different host `phenotypes. Using a combination of parametric and non-parametric artificial neural network analyses we have identified key genes and regulatory pathways which may be important in early and adaptive responses to TB. Using comparisons between data outputs of each analytical pipeline and comparisons with previously published Human TB datasets, we have delineated a subset of gene entities which may be of use for biomarker diagnostic test development. PMID:27228113

Interlinkage among cardio-metabolic disease markers in an urban poor setting in Nairobi, Kenya.

PubMed

Haregu, Tilahun Nigatu; Oti, Samuel; Ngomi, Nicholas; Khayeka-Wandabwa, Christopher; Egondi, Thaddaeus; Kyobutungi, Catherine

2016-01-01

The main cardio-metabolic diseases - mostly cardiovascular diseases such as stroke and ischemic heart disease - share common clinical markers such as raised blood pressure and blood glucose. The pathways of development of many of these conditions are also interlinked. In this regard, a higher level of co-occurrence of the main cardio-metabolic disease markers is expected. Evidence about the patterns of occurrence of cardio-metabolic markers and their interlinkage in the sub-Saharan African setting is inadequate. The goal of the study was to describe the interlinkage among common cardio-metabolic disease markers in an African setting. We used data collected in a cross-sectional study from 5,190 study participants as part of cardiovascular disease risk assessment in the urban slums of Nairobi, Kenya. Five commonly used clinical markers of cardio-metabolic conditions were considered in this analysis. These markers were waist circumference, blood pressure, random blood glucose, total blood cholesterol, and triglyceride levels. Patterns of these markers were described using means, standard deviations, and proportions. The associations between the markers were determined using odds ratios. The weighted prevalence of central obesity, hypertension, hyperglycemia, hypercholesterolemia, and hypertriglyceridemia were 12.3%, 7.0%, 2.5%, 10.3%, and 17.3%, respectively. Women had a higher prevalence of central obesity and hypercholesterolemia as compared to men. Blood glucose was strongly associated with central obesity, blood pressure, and triglyceride levels, whereas the association between blood glucose and total blood cholesterol was not statistically significant. This study shows that most of the common cardio-metabolic markers are interlinked, suggesting a higher probability of comorbidity due to cardio-metabolic conditions and thus the need for integrated approaches.

Has there been a change in the knowledge of GP registrars between 2011 and 2016 as measured by performance on common items in the Applied Knowledge Test?

PubMed

Neden, Catherine A; Parkin, Claire; Blow, Carol; Siriwardena, Aloysius Niroshan

2018-05-08

The aim of this study was to assess whether the absolute standard of candidates sitting the MRCGP Applied Knowledge Test (AKT) between 2011 and 2016 had changed. It is a descriptive study comparing the performance on marker questions of a reference group of UK graduates taking the AKT for the first time between 2011 and 2016. Using aggregated examination data, the performance of individual 'marker' questions was compared using Pearson's chi-squared tests and trend-line analysis. Binary logistic regression was used to analyse changes in performance over the study period. Changes in performance of individual marker questions using Pearson's chi-squared test showed statistically significant differences in 32 of the 49 questions included in the study. Trend line analysis showed a positive trend in 29 questions and a negative trend in the remaining 23. The magnitude of change was small. Logistic regression did not demonstrate any evidence for a change in the performance of the question set over the study period. However, candidates were more likely to get items on administration wrong compared with clinical medicine or research. There was no evidence of a change in performance of the question set as a whole.

Serotonin, neural markers, and memory

PubMed Central

Meneses, Alfredo

2015-01-01

Diverse neuropsychiatric disorders present dysfunctional memory and no effective treatment exits for them; likely as result of the absence of neural markers associated to memory. Neurotransmitter systems and signaling pathways have been implicated in memory and dysfunctional memory; however, their role is poorly understood. Hence, neural markers and cerebral functions and dysfunctions are revised. To our knowledge no previous systematic works have been published addressing these issues. The interactions among behavioral tasks, control groups and molecular changes and/or pharmacological effects are mentioned. Neurotransmitter receptors and signaling pathways, during normal and abnormally functioning memory with an emphasis on the behavioral aspects of memory are revised. With focus on serotonin, since as it is a well characterized neurotransmitter, with multiple pharmacological tools, and well characterized downstream signaling in mammals' species. 5-HT1A, 5-HT4, 5-HT5, 5-HT6, and 5-HT7 receptors as well as SERT (serotonin transporter) seem to be useful neural markers and/or therapeutic targets. Certainly, if the mentioned evidence is replicated, then the translatability from preclinical and clinical studies to neural changes might be confirmed. Hypothesis and theories might provide appropriate limits and perspectives of evidence. PMID:26257650

Potential Role of Neuroimaging Markers for Early Diagnosis of Dementia in Primary Care.

PubMed

Teipel, Stefan; Kilimann, Ingo; Thyrian, Jochen R; Kloppel, Stefan; Hoffmann, Wolfgang

2018-01-01

The use of imaging markers for the diagnosis of predementia and early dementia stages of Alzheimer's disease (AD) has widely been explored in research settings and specialized care. The use of these markers in primary care has yet to be established. Summarize current evidence for the usefulness of imaging markers for AD in primary compared to specialized care settings. Selective overview of the literature, and pilot data on the use of MRI-based hippocampus and basal forebrain volumetry for the discrimination of AD dementia and mild cognitive impairment (MCI) cases from healthy controls in 58 cases from a primary care cohort and 58 matched cases from a memory clinic's sample. Molecular imaging marker of amyloid pathology, and volumetric markers of regional and whole brain atrophy support the diagnosis of AD dementia and MCI due to AD, and contribute to confidence in the differential diagnosis of AD and non-AD related dementias in specialized care. Limited evidence from the literature and our primary care cohort suggests that the diagnostic accuracy of volumetric imaging markers may be similar in the dementia stage of AD, but may be inferior for cases with MCI in primary compared with specialized care. Evidence is still widely lacking on the use of imaging markers for early and differential diagnosis of AD dementia, and detection of prodromal AD in primary care. Further progress to fill this gap will depend on the availability of international multimodal data from well-defined primary care cohorts. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Forensic DNA methylation profiling from evidence material for investigative leads

PubMed Central

Lee, Hwan Young; Lee, Soong Deok; Shin, Kyoung-Jin

2016-01-01

DNA methylation is emerging as an attractive marker providing investigative leads to solve crimes in forensic genetics. The identification of body fluids that utilizes tissue-specific DNA methylation can contribute to solving crimes by predicting activity related to the evidence material. The age estimation based on DNA methylation is expected to reduce the number of potential suspects, when the DNA profile from the evidence does not match with any known person, including those stored in the forensic database. Moreover, the variation in DNA implicates environmental exposure, such as cigarette smoking and alcohol consumption, thereby suggesting the possibility to be used as a marker for predicting the lifestyle of potential suspect. In this review, we describe recent advances in our understanding of DNA methylation variations and the utility of DNA methylation as a forensic marker for advanced investigative leads from evidence materials. [BMB Reports 2016; 49(7): 359-369] PMID:27099236

Genes, age, and alcoholism: analysis of GAW14 data.

PubMed

Apprey, Victor; Afful, Joseph; Harrell, Jules P; Taylor, Robert E; Bonney, George E

2005-12-30

A genetic analysis of age of onset of alcoholism was performed on the Collaborative Study on the Genetics of Alcoholism data released for Genetic Analysis Workshop 14. Our study illustrates an application of the log-normal age of onset model in our software Genetic Epidemiology Models (GEMs). The phenotype ALDX1 of alcoholism was studied. The analysis strategy was to first find the markers of the Affymetrix SNP dataset with significant association with age of onset, and then to perform linkage analysis on them. ALDX1 revealed strong evidence of linkage for marker tsc0041591 on chromosome 2 and suggestive linkage for marker tsc0894042 on chromosome 3. The largest separation in mean ages of onset of ALDX1 was 19.76 and 24.41 between male smokers who are carriers of the risk allele of tsc0041591 and the non-carriers, respectively. Hence, male smokers who are carriers of marker tsc0041591 on chromosome 2 have an average onset of ALDX1 almost 5 years earlier than non-carriers.

An investigation of candidate regions for association with bipolar disorder.

PubMed

Knight, Jo; Rochberg, Nanette S; Saccone, Scott F; Nurnberger, John I; Rice, John P

2010-10-05

We performed a case-control study of 1,000 cases and 1,028 controls on 1,509 markers, 1,139 of which were located in a 8 Mb region on chromosome 6 (105-113 Mb). This region has shown evidence of involvement in bipolar disorder (BP) in a number of other studies. We find association between BP and two SNPs in the gene LACE1. SNP rs9486880 and rs11153113 (both have P-values of 2 × 10(-5)). Both P-values are in the top 5% of the distribution derived from null simulations (P = 0.02 and 0.01, respectively). LACE is a good candidate for BP; it is an ATPase. We genotyped 173 other markers in 17 other positional and/or functional loci but found no further evidence of association with BP.

Increased error-related brain activity distinguishes generalized anxiety disorder with and without comorbid major depressive disorder.

PubMed

Weinberg, Anna; Klein, Daniel N; Hajcak, Greg

2012-11-01

Generalized anxiety disorder (GAD) and major depressive disorder (MDD) are so frequently comorbid that some have suggested that the 2 should be collapsed into a single overarching "distress" disorder. Yet there is also increasing evidence that the 2 categories are not redundant. Neurobehavioral markers that differentiate GAD and MDD would be helpful in ongoing efforts to refine classification schemes based on neurobiological measures. The error-related negativity (ERN) may be one such marker. The ERN is an event-related potential component presenting as a negative deflection approximately 50 ms following an erroneous response and reflects activity of the anterior cingulate cortex. There is evidence for an enhanced ERN in individuals with GAD, but the literature in MDD is mixed. The present study measured the ERN in 26 GAD, 23 comorbid GAD and MDD, and 36 control participants, all of whom were female and medication-free. Consistent with previous research, the GAD group was characterized by a larger ERN and an increased difference between error and correct trials than controls. No such enhancement was evident in the comorbid group, suggesting comorbid depression may moderate the relationship between the ERN and anxiety. The present study further suggests that the ERN is a potentially useful neurobiological marker for future studies that consider the pathophysiology of multiple disorders in order to construct or refine neurobiologically based diagnostic phenotypes. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

Effects of vitamin K in postmenopausal women: mini review.

PubMed

Guralp, Onur; Erel, Cemal Tamer

2014-03-01

Possible benefits of vitamin K on bone health, fracture risk, markers of bone formation and resorption, cardiovascular health, and cancer risk in postmenopausal women have been investigated for over three decades; yet there is no clear evidence-based universal recommendation for its use. Interventional studies showed that vitamin K1 provided significant improvement in undercarboxylated osteocalcin (ucOC) levels in postmenopausal women with normal bone mineral density (BMD); however, there are inconsistent results in women with low BMD. There is no study showing any improvement in bone-alkaline-phosphatase (BAP), n-telopeptide of type-1 collagen (NTX), 25-hydroxy-vitamin D, and urinary markers. Improvement in BMD could not be shown in the majority of the studies; there is no interventional study evaluating the fracture risk. Studies evaluating the isolated effects of menatetrenone (MK-4) showed significant improvement in osteocalcin (OC); however, there are inconsistent results on BAP, NTX, and urinary markers. BMD was found to be significantly increased in the majority of studies. The fracture risk was assessed in three studies, which showed decreased fracture risk to some extent. Although there are proven beneficial effects on some of the bone formation markers, there is not enough evidence-based data to support a role for vitamin K supplementation in osteoporosis prevention among healthy, postmenopausal women receiving vitamin D and calcium supplementation. Interventional studies investigating the isolated role of vitamin K on cardiovascular health are required. Longterm clinical trials are required to evaluate the effect of vitamin K on gynecological cancers. MK-4 seems safe even at doses as high as 45 mg/day. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Molecular evidence of hybridization in sympatric populations of the Enantia jethys complex (Lepidoptera: Pieridae).

PubMed

Jasso-Martínez, Jovana M; Machkour-M'Rabet, Salima; Vila, Roger; Rodríguez-Arnaiz, Rosario; Castañeda-Sortibrán, América Nitxin

2018-01-01

Hybridization events are frequently demonstrated in natural butterfly populations. One interesting butterfly complex species is the Enantia jethys complex that has been studied for over a century; many debates exist regarding the species composition of this complex. Currently, three species that live sympatrically in the Gulf slope of Mexico (Enantia jethys, E. mazai, and E. albania) are recognized in this complex (based on morphological and molecular studies). Where these species live in sympatry, some cases of interspecific mating have been observed, suggesting hybridization events. Considering this, we employed a multilocus approach (analyses of mitochondrial and nuclear sequences: COI, RpS5, and Wg; and nuclear dominant markers: inter-simple sequence repeat (ISSRs) to study hybridization in sympatric populations from Veracruz, Mexico. Genetic diversity parameters were determined for all molecular markers, and species identification was assessed by different methods such as analyses of molecular variance (AMOVA), clustering, principal coordinate analysis (PCoA), gene flow, and PhiPT parameters. ISSR molecular markers were used for a more profound study of hybridization process. Although species of the Enantia jethys complex have a low dispersal capacity, we observed high genetic diversity, probably reflecting a high density of individuals locally. ISSR markers provided evidence of a contemporary hybridization process, detecting a high number of hybrids (from 17% to 53%) with significant differences in genetic diversity. Furthermore, a directional pattern of hybridization was observed from E. albania to other species. Phylogenetic study through DNA sequencing confirmed the existence of three clades corresponding to the three species previously recognized by morphological and molecular studies. This study underlines the importance of assessing hybridization in evolutionary studies, by tracing the lineage separation process that leads to the origin of new species. Our research demonstrates that hybridization processes have a high occurrence in natural populations.

Principal component for metabolic syndrome risk maps to chromosome 4p in Mexican Americans: the San Antonio Family Heart Study.

PubMed

Cai, Guowen; Cole, Shelley A; Freeland-Graves, Jeanne H; MacCluer, Jean W; Blangero, John; Comuzzie, Anthony G

2004-10-01

Metabolic syndrome refers to the clustering of disease conditions such as insulin resistance, hyperinsulinemia, dyslipidemia, hypertension, and obesity. To explore the genetic predispositions of this complex syndrome, we conducted a principal components analysis using data on 14 phenotypes related to the risk of developing metabolic syndrome. The subjects were 566 nondiabetic Mexican Americans, distributed in 41 extended families from the San Antonio Family Heart Study. The factor scores obtained from these 14 phenotypes were used in multipoint linkage analysis using SOLAR. Factors were identified that accounted for 73% of the total variance of the original variables: body size-adiposity, insulin-glucose, blood pressure, and lipid levels. Each factor exhibited evidence for either significant or suggestive linkage involving four factor-specific chromosomal regions relating to chromosomes 1, 3, 4, and 6. Significant evidence for linkage of the lipid factor was found on chromosome 4 near marker D4S403 (LOD = 3.52), where the cholecystokinin A receptor (CCKAR) and ADP-ribosyl cyclase 1 (CD38) genes are located. Suggestive evidence for linkage of the body size-adiposity factor to chromosome 1 near marker D1S1597 (LOD = 2.53) in the region containing the nuclear receptor subfamily 0, group B, member 2 gene (NROB2) also was observed. The insulin-glucose and blood pressure factors were linked suggestively to regions on chromosome 3 near marker D3S1595 (LOD = 2.20) and on chromosome 6 near marker D6S 1031 (LOD = 2.08), respectively. In summary, our findings suggest that the factor structures for the risk of metabolic syndrome are influenced by multiple distinct genes across the genome.

Biological pathways, candidate genes and molecular markers associated with quality-of-life domains: an update

PubMed Central

Sprangers, Mirjam A.G.; Thong, Melissa S.Y.; Bartels, Meike; Barsevick, Andrea; Ordoñana, Juan; Shi, Qiuling; Wang, Xin Shelley; Klepstad, Pål; Wierenga, Eddy A.; Singh, Jasvinder A.; Sloan, Jeff A.

2014-01-01

Background There is compelling evidence of a genetic foundation of patient-reported QOL. Given the rapid development of substantial scientific advances in this area of research, the current paper updates and extends reviews published in 2010. Objectives The objective is to provide an updated overview of the biological pathways, candidate genes and molecular markers involved in fatigue, pain, negative (depressed mood) and positive (well-being/happiness) emotional functioning, social functioning, and overall QOL. Methods We followed a purposeful search algorithm of existing literature to capture empirical papers investigating the relationship between biological pathways and molecular markers and the identified QOL domains. Results Multiple major pathways are involved in each QOL domain. The inflammatory pathway has the strongest evidence as a controlling mechanism underlying fatigue. Inflammation and neurotransmission are key processes involved in pain perception and the COMT gene is associated with multiple sorts of pain. The neurotransmitter and neuroplasticity theories have the strongest evidence for their relationship with depression. Oxytocin-related genes and genes involved in the serotonergic and dopaminergic pathways play a role in social functioning. Inflammatory pathways, via cytokines, also play an important role in overall QOL. Conclusions Whereas the current findings need future experiments and replication efforts, they will provide researchers supportive background information when embarking on studies relating candidate genes and/or molecular markers to QOL domains. The ultimate goal of this area of research is to enhance patients’ QOL. PMID:24604075

Biological pathways, candidate genes, and molecular markers associated with quality-of-life domains: an update.

PubMed

Sprangers, Mirjam A G; Thong, Melissa S Y; Bartels, Meike; Barsevick, Andrea; Ordoñana, Juan; Shi, Qiuling; Wang, Xin Shelley; Klepstad, Pål; Wierenga, Eddy A; Singh, Jasvinder A; Sloan, Jeff A

2014-09-01

There is compelling evidence of a genetic foundation of patient-reported quality of life (QOL). Given the rapid development of substantial scientific advances in this area of research, the current paper updates and extends reviews published in 2010. The objective was to provide an updated overview of the biological pathways, candidate genes, and molecular markers involved in fatigue, pain, negative (depressed mood) and positive (well-being/happiness) emotional functioning, social functioning, and overall QOL. We followed a purposeful search algorithm of existing literature to capture empirical papers investigating the relationship between biological pathways and molecular markers and the identified QOL domains. Multiple major pathways are involved in each QOL domain. The inflammatory pathway has the strongest evidence as a controlling mechanism underlying fatigue. Inflammation and neurotransmission are key processes involved in pain perception, and the catechol-O-methyltransferase (COMT) gene is associated with multiple sorts of pain. The neurotransmitter and neuroplasticity theories have the strongest evidence for their relationship with depression. Oxytocin-related genes and genes involved in the serotonergic and dopaminergic pathways play a role in social functioning. Inflammatory pathways, via cytokines, also play an important role in overall QOL. Whereas the current findings need future experiments and replication efforts, they will provide researchers supportive background information when embarking on studies relating candidate genes and/or molecular markers to QOL domains. The ultimate goal of this area of research is to enhance patients' QOL.

Evidence for Linkage of Bipolar Disorder to Chromosome 18 with a Parent-of-Origin Effect

PubMed Central

Stine, O. Colin; Xu, Jianfeng; Koskela, Rebecca; McMahon, Francis J.; Gschwend, Michele; Friddle, Carl; Clark, Chris D.; McInnis, Melvin G.; Simpson, Sylvia G.; Breschel, Theresa S.; Vishio, Eva; Riskin, Kelly; Feilotter, Harriet; Chen, Eugene; Shen, Susan; Folstein, Susan; Meyers, Deborah A.; Botstein, David; Marr, Thomas G.; DePaulo, J. Raymond

1995-01-01

A susceptibility gene on chromosome 18 and a parent-of-origin effect have been suggested for bipolar affective disorder (BPAD). We have studied 28 nuclear families selected for apparent unilineal transmission of the BPAD phenotype, by using 31 polymorphic markers spanning chromosome 18. Evidence for linkage was tested with affected-sib-pair and LOD score methods under two definitions of the affected phenotype. The affected-sib-pair analyses indicated excess allele sharing for markers on 18p within the region reported previously. The greatest sharing was at D18S37: 64% in bipolar and recurrent unipolar (RUP) sib pairs (P = .0006). In addition, excess sharing of the paternally, but not maternally, transmitted alleles was observed at three markers on 18q: at D18S41, 51 bipolar and RUP sib pairs were concordant for paternally transmitted alleles, and 21 pairs were discordant (P = .0004). The evidence for linkage to loci on both 18p and 18q was strongest in the 11 paternal pedigrees, i.e., those in which the father or one of the father's sibs is affected. In these pedigrees, the greatest allele sharing (81%; P = .00002) and the highest LOD score (3.51; θ = 0.0) were observed at D18S41. Our results provide further support for linkage of BPAD to chromosome 18 and the first molecular evidence for a parent-of-origin effect operating in this disorder. The number of loci involved, and their precise location, require further study. PMID:8533768

The writer's guide to education scholarship in emergency medicine: Education innovations (part 3).

PubMed

Hall, Andrew K; Hagel, Carly; Chan, Teresa M; Thoma, Brent; Murnaghan, Aleisha; Bhanji, Farhan

2018-05-01

The scholarly dissemination of innovative medical education practices helps broaden the reach of this type of work, allowing scholarship to have an impact beyond a single institution. There is little guidance in the literature for those seeking to publish program evaluation studies and innovation papers. This study aims to derive a set of evidence-based features of high-quality reports on innovations in emergency medicine (EM) education. We conducted a scoping review and thematic analysis to determine quality markers for medical education innovation reports, with a focus on EM. A search of MEDLINE, EMBASE, ERIC, and Google Scholar was augmented by a hand search of relevant publication guidelines, guidelines for authors, and website submission portals from medical education and EM journals. Study investigators reviewed the selected articles, and a thematic analysis was conducted. Our search strategy identified 14 relevant articles from which 34 quality markers were extracted. These markers were grouped into seven important themes: goals and need for innovation, preparation, innovation development, innovation implementation, evaluation of innovation, evidence of reflective practice, and reporting and dissemination. In addition, multiple outlets for the publication of EM education innovations were identified and compiled. The publication and dissemination of innovations are critical for the EM education community and the training of health professionals. We anticipate that our list of innovation report quality markers will be used by EM education innovators to support the dissemination of novel educational practices.

Identification of genetic markers associated with Gilles de la Tourette syndrome in an Afrikaner population.

PubMed Central

Simonic, I; Gericke, G S; Ott, J; Weber, J L

1998-01-01

Because gene-mapping efforts, using large kindreds and parametric methods of analysis, for the neurologic disorder Tourette syndrome have failed, efforts are being redirected toward association studies in young, genetically isolated populations. The availability of dense marker maps makes it feasible to search for association throughout the entire genome. We report the results of such a genome scan using DNA samples from Tourette patients and unaffected control subjects from the South African Afrikaner population. To optimize mapping efficiency, we chose a two-step strategy. First, we screened pools of DNA samples from both affected and control individuals, using a dense collection of 1,167 short tandem-repeat polymorphisms distributed throughout the genome. Second, we typed those markers displaying evidence of allele frequency-distribution shifts, along with additional tightly linked markers, using DNA from each affected and unaffected individual. To reduce false positives, we tested two independent groups of case and control subjects. Strongest evidence for association (P values 10-2 to 10-5) were obtained for markers within chromosomal regions encompassing D2S1790 near the chromosome 2 centromere, D6S477 on distal 6p, D8S257 on 8q, D11S933 on 11q, D14S1003 on proximal 14q, D20S1085 on distal 20q, and D21S1252 on 21q. PMID:9718333

Identification of genetic markers associated with Gilles de la Tourette syndrome in an Afrikaner population.

PubMed

Simonic, I; Gericke, G S; Ott, J; Weber, J L

1998-09-01

Because gene-mapping efforts, using large kindreds and parametric methods of analysis, for the neurologic disorder Tourette syndrome have failed, efforts are being redirected toward association studies in young, genetically isolated populations. The availability of dense marker maps makes it feasible to search for association throughout the entire genome. We report the results of such a genome scan using DNA samples from Tourette patients and unaffected control subjects from the South African Afrikaner population. To optimize mapping efficiency, we chose a two-step strategy. First, we screened pools of DNA samples from both affected and control individuals, using a dense collection of 1,167 short tandem-repeat polymorphisms distributed throughout the genome. Second, we typed those markers displaying evidence of allele frequency-distribution shifts, along with additional tightly linked markers, using DNA from each affected and unaffected individual. To reduce false positives, we tested two independent groups of case and control subjects. Strongest evidence for association (P values 10-2 to 10-5) were obtained for markers within chromosomal regions encompassing D2S1790 near the chromosome 2 centromere, D6S477 on distal 6p, D8S257 on 8q, D11S933 on 11q, D14S1003 on proximal 14q, D20S1085 on distal 20q, and D21S1252 on 21q.

Evidence for chromosome 2p16.3 polycystic ovary syndrome susceptibility locus in affected women of European ancestry.

PubMed

Mutharasan, Priscilla; Galdones, Eugene; Peñalver Bernabé, Beatriz; Garcia, Obed A; Jafari, Nadereh; Shea, Lonnie D; Woodruff, Teresa K; Legro, Richard S; Dunaif, Andrea; Urbanek, Margrit

2013-01-01

A previous genome-wide association study in Chinese women with polycystic ovary syndrome (PCOS) identified a region on chromosome 2p16.3 encoding the LH/choriogonadotropin receptor (LHCGR) and FSH receptor (FSHR) genes as a reproducible PCOS susceptibility locus. The objective of the study was to determine the role of the LHCGR and/or FSHR gene in the etiology of PCOS in women of European ancestry. This was a genetic association study in a European ancestry cohort of women with PCOS. The study was conducted at an academic medical center. Participants in the study included 905 women with PCOS diagnosed by National Institutes of Health criteria and 956 control women. We genotyped 94 haplotype-tagging single-nucleotide polymorphisms and two coding single-nucleotide polymorphisms mapping to the coding region of LHCGR and FSHR plus 20 kb upstream and downstream of the genes and test for association in the case control cohort and for association with nine quantitative traits in the women with PCOS. We found strong evidence for an association of PCOS with rs7562215 (P = 0.0037) and rs10495960 (P = 0.0046). Although the marker with the strongest association in the Chinese PCOS genome-wide association study (rs13405728) was not informative in the European populations, we identified and genotyped three markers (rs35960650, rs2956355, and rs7562879) within 5 kb of rs13405728. Of these, rs7562879 was nominally associated with PCOS (P = 0.020). The strongest evidence for association mapping to FSHR was observed with rs1922476 (P = 0.0053). Furthermore, markers with the FSHR gene region were associated with FSH levels in women with PCOS. Fine mapping of the chromosome 2p16.3 Chinese PCOS susceptibility locus in a European ancestry cohort provides evidence for association with two independent loci and PCOS. The gene products LHCGR and FSHR therefore are likely to be important in the etiology of PCOS, regardless of ethnicity.

Evidence mapping of whole grain intervention studies, health outcomes, and reporting practices

USDA-ARS?s Scientific Manuscript database

Higher consumption of whole grain foods is associated with reduced risk of cardiovascular disease, diabetes, and obesity in observational studies; yet, in intervention studies, the effect of whole grains on intermediate markers of risk are mixed. This may be due to the variability in study design, d...

Factor Structure and Validity of Paper-and-Pencil Measures of Mental Speed: Evidence for a Higher-Order Model?

ERIC Educational Resources Information Center

Danthiir, Vanessa; Wilhelm, Oliver; Schulze, Ralf; Roberts, Richard D.

2005-01-01

This study explored the structure of elementary cognitive tasks (ECTs) and relations between the corresponding construct(s) with processing speed (Gs) and fluid intelligence (Gf). Participants (N=321) completed 14 ECTs, 3 Gs, and 6 Gf marker tests, all administered in paper-and-pencil format to reduce potential confounds evident when tasks are…

Bidirectional Prospective Associations Between Cardiac Autonomic Activity and Inflammatory Markers.

PubMed

Hu, Mandy Xian; Lamers, Femke; Neijts, Melanie; Willemsen, Gonneke; de Geus, Eco J C; Penninx, Brenda W J H

2018-06-01

Autonomic nervous system (ANS) imbalance has been cross-sectionally associated with inflammatory processes. Longitudinal studies are needed to shed light on the nature of this relationship. We examined cross-sectional and bidirectional prospective associations between cardiac autonomic measures and inflammatory markers. Analyses were conducted with baseline (n = 2823), 2-year (n = 2099), and 6-year (n = 1774) data from the Netherlands Study of Depression and Anxiety. To compare the pattern of results, prospective analyses with ANS (during sleep, leisure time, and work) and inflammation were conducted in two data sets from the Netherlands Twin Register measured for 4.9 years (n = 356) and 5.4 years (n = 472). Autonomic nervous system measures were heart rate (HR) and respiratory sinus arrhythmia (RSA). Inflammatory markers were C-reactive protein (CRP) and interleukin (IL)-6. The Netherlands Study of Depression and Anxiety results showed that higher HR and lower RSA were cross-sectionally significantly associated with higher inflammatory levels. Higher HR predicted higher levels of CRP (B = .065, p < .001) and IL-6 (B = .036, p = .014) at follow-up. Higher CRP levels predicted lower RSA (B = -.024, p = .048) at follow-up. The Netherlands Twin Register results confirmed that higher HR was associated with higher CRP and IL-6 levels 4.9 years later. Higher IL-6 levels predicted higher HR and lower RSA at follow-up. Autonomic imbalance is associated with higher levels of inflammation. Independent data from two studies converge in evidence that higher HR predicts subsequent higher levels of CRP and IL-6. Inflammatory markers may also predict future ANS activity, but evidence for this was less consistent.

A SOMATIC-MARKER THEORY OF ADDICTION

PubMed Central

Verdejo-García, Antonio; Bechara, Antoine

2009-01-01

Similar to patients with ventromedial prefrontal cortex (VMPC) lesions, substance abusers show altered decision-making, characterized by a tendency to choose the immediate reward, at the expense of negative future consequences. The somatic-marker model proposes that decision-making depends on neural substrates that regulate homeostasis, emotion and feeling. According to this model, there should be a link between alterations in processing emotions in substance abusers, and their impairments in decision-making. A growing evidence from neuroscientific studies indicate that core aspects of addiction may be explained in terms of abnormal emotional/homeostatic guidance of decision-making. Behavioural studies have revealed emotional processing and decision-making deficits in substance abusers. Neuroimaging studies have shown that altered decision-making in addiction is associated with abnormal functioning of a distributed neural network critical for the processing of emotional information, and the experience of “craving”, including the VMPC, the amygdala, the striatum, the anterior cingulate cortex, and the insular/somato-sensory cortices, as well as non-specific neurotransmitter systems that modulate activities of neural processes involved in decision-making. The aim of this paper is to review this growing evidence, and to examine the extent of which these studies support a somatic-marker theory of addiction. We conclude that there are at least two underlying types of dysfunctions where emotional signals (somatic-markers) turns in favor of immediate outcomes in addiction: (1) a hyperactivity in the amygdala or impulsive system, which exaggerates the rewarding impact of available incentives, and (2) hypoactivity in the prefrontal cortex or reflective system, which forecasts the long-term consequences of a given action. PMID:18722390

Phylogenetic study of Geitlerinema and Microcystis (Cyanobacteria) using PC-IGS and 16S-23S ITS as markers: investigation of horizontal gene transfer.

PubMed

Piccin-Santos, Viviane; Brandão, Marcelo Mendes; Bittencourt-Oliveira, Maria Do Carmo

2014-08-01

Selection of genes that have not been horizontally transferred for prokaryote phylogenetic inferences is regarded as a challenging task. The markers internal transcribed spacer of ribosomal genes (16S-23S ITS) and phycocyanin intergenic spacer (PC-IGS), based on the operons of ribosomal and phycocyanin genes respectively, are among the most used markers in cyanobacteria. The region of the ribosomal genes has been considered stable, whereas the phycocyanin operon may have undergone horizontal transfer. To investigate the occurrence of horizontal transfer of PC-IGS, phylogenetic trees of Geitlerinema and Microcystis strains were generated using PC-IGS and 16S-23S ITS and compared. Phylogenetic trees based on the two markers were mostly congruent for Geitlerinema and Microcystis, indicating a common evolutionary history among ribosomal and phycocyanin genes with no evidence for horizontal transfer of PC-IGS. Thus, PC-IGS is a suitable marker, along with 16S-23S ITS for phylogenetic studies of cyanobacteria. © 2014 Phycological Society of America.

Using genetic markers to orient the edges in quantitative trait networks: the NEO software.

PubMed

Aten, Jason E; Fuller, Tova F; Lusis, Aldons J; Horvath, Steve

2008-04-15

Systems genetic studies have been used to identify genetic loci that affect transcript abundances and clinical traits such as body weight. The pairwise correlations between gene expression traits and/or clinical traits can be used to define undirected trait networks. Several authors have argued that genetic markers (e.g expression quantitative trait loci, eQTLs) can serve as causal anchors for orienting the edges of a trait network. The availability of hundreds of thousands of genetic markers poses new challenges: how to relate (anchor) traits to multiple genetic markers, how to score the genetic evidence in favor of an edge orientation, and how to weigh the information from multiple markers. We develop and implement Network Edge Orienting (NEO) methods and software that address the challenges of inferring unconfounded and directed gene networks from microarray-derived gene expression data by integrating mRNA levels with genetic marker data and Structural Equation Model (SEM) comparisons. The NEO software implements several manual and automatic methods for incorporating genetic information to anchor traits. The networks are oriented by considering each edge separately, thus reducing error propagation. To summarize the genetic evidence in favor of a given edge orientation, we propose Local SEM-based Edge Orienting (LEO) scores that compare the fit of several competing causal graphs. SEM fitting indices allow the user to assess local and overall model fit. The NEO software allows the user to carry out a robustness analysis with regard to genetic marker selection. We demonstrate the utility of NEO by recovering known causal relationships in the sterol homeostasis pathway using liver gene expression data from an F2 mouse cross. Further, we use NEO to study the relationship between a disease gene and a biologically important gene co-expression module in liver tissue. The NEO software can be used to orient the edges of gene co-expression networks or quantitative trait networks if the edges can be anchored to genetic marker data. R software tutorials, data, and supplementary material can be downloaded from: http://www.genetics.ucla.edu/labs/horvath/aten/NEO.

Screening injured children for physical abuse or neglect in emergency departments: a systematic review.

PubMed

Woodman, J; Lecky, F; Hodes, D; Pitt, M; Taylor, B; Gilbert, Ruth

2010-03-01

Screening markers are used in emergency departments (EDs) to identify children who should be assessed for possible physical abuse and neglect. We conducted three systematic reviews evaluating age, repeat attendance and injury type as markers for physical abuse or neglect in injured children attending EDs. We included studies comparing markers in physically abused or neglected children and non-abused injured children attending ED or hospital. We calculated likelihood ratios (LRs) for age group, repeat attendance and injury type (head injury, bruises, fractures, burns or other). Given the low prevalence of abuse or neglect, we considered that an LR of 10 or more would be clinically useful. All studies were poor quality. Infancy increased the risk of physical abuse or neglect in severely injured or admitted children (LRs 7.7-13.0, 2 studies) but was not strongly associated in children attending the ED (LR 1.5, 95% CI: 0.9, 2.8; one study). Repeat attendance did not substantially increase the risk of abuse or neglect and may be confounded by chronic disease and socio-economic status (LRs 0.8-3.9, 3 studies). One study showed no evidence that the type of injury substantially increased the risk of physical abuse or neglect in severely injured children. There was no evidence that any of the markers (infancy, type of injury, repeated attendance) were sufficiently accurate (i.e. LR >or= 10) to screen injured children in the ED to identify those requiring paediatric assessment for possible physical abuse or neglect. Clinicians should be aware that among injured children at ED a high proportion of abused children will present without these characteristics and a high proportion of non-abused children will present with them. Information about age, injury type and repeat attendances should be interpreted in this context.

Nuchal translucency in pregnancies conceived after assisted reproduction technology.

PubMed

Hui, Pui Wah; Lee, Chin Peng; Tang, Mary Hoi Yin; Ho, Pak Chung

2006-06-01

Nuchal translucency is one of the important markers in the first trimester during antenatal screening for fetal Down's syndrome. With the observation of alterations in biochemical markers in pregnancies conceived after assisted reproduction, this review presents current information related to the thickness of nuchal translucency in these pregnancies. Early small studies did not demonstrate any discrepancy in the thickness of nuchal translucency in fetuses from assisted reproduction and from spontaneous pregnancies, but there has been recent evidence to suggest an increased level of nuchal translucency in singletons from various modes of assisted-reproduction technology. Nuchal translucency in twins following assisted reproduction did not, however, show a similar increase. Although the effect of chorionicity was not specifically addressed, nuchal translucency thickness in twins born after assisted reproduction was reported to be comparable to that in spontaneous singletons. It is possible that singletons and twins after assisted reproduction exhibit different antenatal behavior and pregnancy courses. Similar to other biochemical markers of fetal Down's syndrome, nuchal translucency is increased in singletons after assisted-reproduction technology. Further studies on twin pregnancies, in particular dichorionic twins, are necessary before conclusive evidence can be drawn for multiple pregnancies.

Significant evidence for linkage disequilibrium over a 5-cM region among Afrikaners.

PubMed

Gordon, D; Simonic, I; Ott, J

2000-05-15

We explore the extent of deviations from Hardy-Weinberg equilibrium (HWE) at a marker locus and linkage disequilibrium (LD) between pairs of marker loci in the Afrikaner population of South Africa. DNA samples were used for genotyping of 23 loci on six chromosomes. The samples were collected from 91 healthy unrelated Afrikaner adults. Exact tests were used to determine evidence for deviations from HWE at a single marker locus or LD between pairs of marker loci. At the 0.05 level of significance, evidence was found for deviation from HWE at only one of the 23 loci. At the same level of significance, LD was found among 8 of the 34 intrachromosomal pairs of loci. On chromosome 21, there was evidence for LD (P = 0.02) between a pair of loci with a genetic distance of 5.51 cM. On chromosome 2, there was evidence for LD between a pair of loci with a genetic distance of 5.28 cM (P = 0.002) and a pair of loci with a genetic distance of 3.68 cM (P = 0.0004). Detailed analysis of LD for one locus pair indicated that only a few of all alleles participated in the LD and that strong LD was most often positive. Our findings indicate that Afrikaans-speaking Afrikaners represent one of those special populations deemed particularly suitable for disequilibrium mapping. Copyright 2000 Academic Press.

Multigene assays and molecular markers in breast cancer: systematic review of health economic analyses.

PubMed

Rouzier, Roman; Pronzato, Paolo; Chéreau, Elisabeth; Carlson, Josh; Hunt, Barnaby; Valentine, William J

2013-06-01

Breast cancer is the most common female cancer and is associated with a significant clinical and economic burden. Multigene assays and molecular markers represent an opportunity to direct chemotherapy only to patients likely to have significant benefit. This systematic review examines published health economic analyses to assess the support for adjuvant therapy decision making. Literature searches of PubMed, the Cochrane Library, and congress databases were carried out to identify economic evaluations of multigene assays and molecular markers published between 2002 and 2012. After screening and data extraction, study quality was assessed using the Quality of Health Economic Studies instrument. The review identified 29 publications that reported evaluations of two assays: Oncotype DX(®) and MammaPrint. Studies of both tests provided evidence that their routine use was cost saving or cost-effective versus conventional approaches. Benefits were driven by optimal allocation of adjuvant chemotherapy and reduction in chemotherapy utilization. Findings were sensitive to variation in the frequency of chemotherapy prescription, chemotherapy costs, and patients' risk profiles. Evidence suggests that multigene assays are likely cost saving or cost-effective relative to current approaches to adjuvant therapy. They should benefit decision making in early-stage breast cancer in a variety of settings worldwide.

The association between immune markers and recent suicide attempts in patients with serious mental illness: A pilot study.

PubMed

Dickerson, Faith; Adamos, Maria; Katsafanas, Emily; Khushalani, Sunil; Origoni, Andrea; Savage, Christina; Schweinfurth, Lucy; Stallings, Cassie; Sweeney, Kevin; Alaedini, Armin; Uhde, Melanie; Severance, Emily; Wilcox, Holly C; Yolken, Robert

2017-09-01

Previous studies have identified elevations in markers of gastrointestinal inflammation in schizophrenia and mood disorders but studies have not measured the association between these markers and recent suicide attempts. We assessed 210 patients receiving treatment for schizophrenia, bipolar disorder, or major depression. We employed the Columbia Suicide Severity Rating Scale to identify recent and lifetime suicide attempts (actual, aborted, and interrupted). Psychiatric participants and a control group of 72 individuals without a psychiatric disorder had a blood sample drawn from which were measured specific markers of gastrointestinal inflammation and also C-Reactive protein (CRP). A total of 20 (10%) of psychiatric participants had a suicide attempt in the previous one month and 95 (45%) an attempt during their lifetime but not in the previous one month. The recent attempters had significantly elevated levels of antibodies to yeast mannan from Saccharomyces cerevisiae (ASCA), the food antigen gliadin, and bacterial lipopolysaccharide (LPS) compared with the non-psychiatric group when adjusting for demographic and clinical variables. These markers were not elevated in individuals with a past, but not recent, suicide attempt history. Our study indicates that there is evidence of gastrointestinal inflammation in some individuals who have had a recent suicide attempt. Copyright © 2017. Published by Elsevier B.V.

A survey of ABCA1 sequence variation confirms association with dementia

PubMed Central

Reynolds, Chandra A.; Hong, Mun-Gwan; Eriksson, Ulrika K.; Blennow, Kaj; Bennet, Anna M.; Johansson, Boo; Malmberg, Bo; Berg, Stig; Wiklund, Fredrik; Gatz, Margaret; Pedersen, Nancy L.; Prince, Jonathan A.

2009-01-01

We and others have conducted targeted genetic association analyses of ABCA1 in relation to Alzheimer disease risk with a resultant mixture of both support and refutation, but all previous studies have been based upon only a few markers. Here, a detailed survey of genetic variation in the ABCA1 region has been performed in a total of 1567 Swedish dementia cases (including 1275 with Alzheimer disease) and 2203 controls, providing evidence of association with maximum significance at marker rs2230805 (OR = 1.39; 95% CI 1.23–1.57, P = 7.7 × 10−8). Haplotype-based tests confirmed association of this genomic region after excluding rs2230805, and imputation did not reveal additional markers with greater support. Significantly associating markers reside in two distinct linkage disequilibrium blocks with maxima near the promoter and in the terminal exon of a truncated ABCA1 splice-form. The putative risk allele of rs2230805 was also found to be associated with reduced cerebrospinal fluid levels of β-amyloid. The strongest evidence of association was obtained when all forms of dementia were considered together, but effect sizes were similar when only confirmed Alzheimer disease cases were assessed. Results further implicate ABCA1 in dementia, reinforcing the putative involvement of lipid transport in neurodegenerative disease. PMID:19606474

Nonsyndromic cleft lip with or without cleft palate: Evidence of linkage to BCL3 in 17 multigenerational families

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

Stein, J.; Hecht, T.; Stal, S.

1995-08-01

Nonsyndromic cleft lip with or without cleft palate (CL/P) is a common craniofacial developmental defect. Recent segregation analyses have suggested that major genes play a role in the etiology of CL/P. Linkage to 22 candidate genes was tested in 11 multigenerational families with CL/P, and 21 of these candidates were excluded. APOC2, 19q13.1, which is linked to the proto-oncogene BCL3, gave suggestive evidence for linkage to CL/P. The study was expanded to include a total of 39 multigenerational CL/P families. Linkage was tested in all families, using anonymous marker, D19S178, and intragenic markers in BCL3 and APOC2. Linkage was testedmore » under two models, autosomal dominant with reduced penetrance and affecteds-only model. Both models showed evidence of heterogeneity, with 43% of families linked at zero recombination to BCL3 when marker data from BCL3 and APOC2 were included. A maximum multipoint LOD score of 7.00 at BCL3 was found among the 17 families that had posterior probabilities {ge}50% in favor of linkage. The transmission disequilibrium test provided additional evidence for linkage with the 3 allele of BCL3 more often transmitted to affected children. These results suggest that BCL3, or a nearby gene, plays a role in the etiology of CL/P in some families. 39 refs., 8 figs., 4 tabs.« less

Emerging Evidence on Neutrophil Motility Supporting Its Usefulness to Define Vitamin C Intake Requirements.

PubMed

Elste, Volker; Troesch, Barbara; Eggersdorfer, Manfred; Weber, Peter

2017-05-16

Establishing intake recommendations for vitamin C remains a challenge, as no suitable functional parameter has yet been agreed upon. In this report, we review the emerging evidence on neutrophil motility as a possible marker of vitamin C requirements and put the results in perspective with other approaches. A recent in vitro study showed that adequate levels of vitamin C were needed for this function to work optimally when measured as chemotaxis and chemokinesis. In a human study, neutrophil motility was optimal at intakes ≥250 mg/day. Interestingly, a Cochrane review showed a significant reduction in the duration of episodes of common cold with regular vitamin C intakes in a similar range. Additionally, it was shown that at a plasma level of 75 µmol/L, which is reached with vitamin C intakes ≥200 mg/day, incidences of cardiovascular disease were lowest. This evidence would suggest that daily intakes of 200 mg vitamin C might be advisable for the general adult population, which can be achieved by means of a diverse diet. However, additional studies are warranted to investigate the usefulness of neutrophil motility as a marker of vitamin C requirements.

Markers of vitamin D metabolism and incidence of clinically diagnosed abdominal aortic aneurysm: The Atherosclerosis Risk in Communities Study.

PubMed

Lutsey, Pamela L; Rooney, Mary R; Folsom, Aaron R; Michos, Erin D; Alonso, Alvaro; Tang, Weihong

2018-06-01

Little is known about whether markers of vitamin D metabolism are associated with the development of abdominal aortic aneurysm (AAA), though these markers have been linked to other cardiovascular diseases. We tested the hypotheses that risk of AAA is higher among individuals with low serum concentrations of 25-hydroxy vitamin D [25(OH)D], and among those with elevated concentrations of calcium, fibroblast growth factor 23 (FGF23), phosphorus, and parathyroid hormone (PTH) using data from a cohort of black and white individuals with long-term follow-up. Markers of vitamin D metabolism were measured using serum collected in 1990-1992 from ARIC study participants (mean ± SD age 56.9 ± 5.7 years, 43.2% male, 23.9% black). A total of 12,770 participants were followed until 2011 for incident AAA. Multivariable-adjusted Cox regression models were used. A total of 449 incident AAA events occurred over a median follow-up of 19.7 years. For the association between serum calcium and risk of incident AAA there was evidence of interaction by sex ( p-interaction 0.02). Among women, in the fully adjusted model, the hazard ratio (95% confidence interval) comparing the highest to lowest quartile was 2.43 (1.25-4.73), whereas in men it was 1.01 (0.72-1.43). Not associated with risk of incident AAA were 25(OH)D, FGF23, phosphorus, and PTH. In this large prospective cohort, there was little evidence that markers of vitamin D metabolism are associated with risk of incident AAA. The positive association of calcium with AAA among women may warrant further investigation and replication in other populations.

Novel Crohn disease locus identified by genome-wide association maps to a gene desert on 5p13.1 and modulates expression of PTGER4.

PubMed

Libioulle, Cécile; Louis, Edouard; Hansoul, Sarah; Sandor, Cynthia; Farnir, Frédéric; Franchimont, Denis; Vermeire, Séverine; Dewit, Olivier; de Vos, Martine; Dixon, Anna; Demarche, Bruno; Gut, Ivo; Heath, Simon; Foglio, Mario; Liang, Liming; Laukens, Debby; Mni, Myriam; Zelenika, Diana; Van Gossum, André; Rutgeerts, Paul; Belaiche, Jacques; Lathrop, Mark; Georges, Michel

2007-04-20

To identify novel susceptibility loci for Crohn disease (CD), we undertook a genome-wide association study with more than 300,000 SNPs characterized in 547 patients and 928 controls. We found three chromosome regions that provided evidence of disease association with p-values between 10(-6) and 10(-9). Two of these (IL23R on Chromosome 1 and CARD15 on Chromosome 16) correspond to genes previously reported to be associated with CD. In addition, a 250-kb region of Chromosome 5p13.1 was found to contain multiple markers with strongly suggestive evidence of disease association (including four markers with p < 10(-7)). We replicated the results for 5p13.1 by studying 1,266 additional CD patients, 559 additional controls, and 428 trios. Significant evidence of association (p < 4 x 10(-4)) was found in case/control comparisons with the replication data, while associated alleles were over-transmitted to affected offspring (p < 0.05), thus confirming that the 5p13.1 locus contributes to CD susceptibility. The CD-associated 250-kb region was saturated with 111 SNP markers. Haplotype analysis supports a complex locus architecture with multiple variants contributing to disease susceptibility. The novel 5p13.1 CD locus is contained within a 1.25-Mb gene desert. We present evidence that disease-associated alleles correlate with quantitative expression levels of the prostaglandin receptor EP4, PTGER4, the gene that resides closest to the associated region. Our results identify a major new susceptibility locus for CD, and suggest that genetic variants associated with disease risk at this locus could modulate cis-acting regulatory elements of PTGER4.

Novel Crohn Disease Locus Identified by Genome-Wide Association Maps to a Gene Desert on 5p13.1 and Modulates Expression of PTGER4

PubMed Central

Libioulle, Cécile; Louis, Edouard; Hansoul, Sarah; Sandor, Cynthia; Farnir, Frédéric; Franchimont, Denis; Vermeire, Séverine; Dewit, Olivier; de Vos, Martine; Dixon, Anna; Demarche, Bruno; Gut, Ivo; Heath, Simon; Foglio, Mario; Liang, Liming; Laukens, Debby; Mni, Myriam; Zelenika, Diana; Gossum, André Van; Rutgeerts, Paul; Belaiche, Jacques; Lathrop, Mark; Georges, Michel

2007-01-01

To identify novel susceptibility loci for Crohn disease (CD), we undertook a genome-wide association study with more than 300,000 SNPs characterized in 547 patients and 928 controls. We found three chromosome regions that provided evidence of disease association with p-values between 10−6 and 10−9. Two of these (IL23R on Chromosome 1 and CARD15 on Chromosome 16) correspond to genes previously reported to be associated with CD. In addition, a 250-kb region of Chromosome 5p13.1 was found to contain multiple markers with strongly suggestive evidence of disease association (including four markers with p < 10−7). We replicated the results for 5p13.1 by studying 1,266 additional CD patients, 559 additional controls, and 428 trios. Significant evidence of association (p < 4 × 10−4) was found in case/control comparisons with the replication data, while associated alleles were over-transmitted to affected offspring (p < 0.05), thus confirming that the 5p13.1 locus contributes to CD susceptibility. The CD-associated 250-kb region was saturated with 111 SNP markers. Haplotype analysis supports a complex locus architecture with multiple variants contributing to disease susceptibility. The novel 5p13.1 CD locus is contained within a 1.25-Mb gene desert. We present evidence that disease-associated alleles correlate with quantitative expression levels of the prostaglandin receptor EP4, PTGER4, the gene that resides closest to the associated region. Our results identify a major new susceptibility locus for CD, and suggest that genetic variants associated with disease risk at this locus could modulate cis-acting regulatory elements of PTGER4. PMID:17447842

Source Identification of Human Biological Materials and Its Prospect in Forensic Science.

PubMed

Zou, K N; Gui, C; Gao, Y; Yang, F; Zhou, H G

2016-06-01

Source identification of human biological materials in crime scene plays an important role in reconstructing the crime process. Searching specific genetic markers to identify the source of different human biological materials is the emphasis and difficulty of the research work of legal medical experts in recent years. This paper reviews the genetic markers which are used for identifying the source of human biological materials and studied widely, such as DNA methylation, mRNA, microRNA, microflora and protein, etc. By comparing the principles and methods of source identification of human biological materials using different kinds of genetic markers, different source of human biological material owns suitable marker types and can be identified by detecting single genetic marker or combined multiple genetic markers. Though there is no uniform standard and method for identifying the source of human biological materials in forensic laboratories at present, the research and development of a series of mature and reliable methods for distinguishing different human biological materials play the role as forensic evidence which will be the future development direction. Copyright© by the Editorial Department of Journal of Forensic Medicine.

How to predict clinical relapse in inflammatory bowel disease patients

PubMed Central

Liverani, Elisa; Scaioli, Eleonora; Digby, Richard John; Bellanova, Matteo; Belluzzi, Andrea

2016-01-01

Inflammatory bowel diseases have a natural course characterized by alternating periods of remission and relapse. Disease flares occur in a random way and are currently unpredictable for the most part. Predictors of benign or unfavourable clinical course are required to facilitate treatment decisions and to avoid overtreatment. The present article provides a literature review of the current evidence on the main clinical, genetic, endoscopic, histologic, serologic and fecal markers to predict aggressiveness of inflammatory bowel disease and discuss their prognostic role, both in Crohn’s disease and ulcerative colitis. No single marker seems to be reliable alone as a flare predictor, even in light of promising evidence regarding the role of fecal markers, in particular fecal calprotectin, which has reported good results recently. In order to improve our daily clinical practice, validated prognostic scores should be elaborated, integrating clinical and biological markers of prognosis. Finally, we propose an algorithm considering clinical history and biological markers to intercept patients with high risk of clinical relapse. PMID:26811644

Radiographic Diagnosis of Pincer-Type Femoroacetabular Impingement: A Systematic Review.

PubMed

Rhee, Chanseok; Le Francois, Tina; Byrd, J W Thomas; Glazebrook, Mark; Wong, Ivan

2017-05-01

Femoroacetabular impingement (FAI) is a well-recognized condition that causes hip pain and can lead to early osteoarthritis if not managed properly. With the increasing awareness and efficacy of operative treatments for pincer-type FAI, there is a need for consensus on the standardized radiographic diagnosis. To perform a systematic review of the evidence regarding imaging modalities and radiographic signs for diagnosing pincer-type FAI. Systematic review; Level of evidence, 4. A literature review was performed in 2016 using the Cochrane, PubMed, and Embase search engines. All articles focusing on a radiographic diagnosis of pincer-type FAI were reviewed. Each of the included 44 articles was assigned the appropriate level of evidence, and the particular radiographic marker and/or type of imaging were also summarized. There were 44 studies included in the final review. Most of the articles were level 4 evidence (26 articles), and there were 12 level 3 and 6 level 2 articles. The crossover sign was the most commonly used radiographic sign (27/44) followed by the lateral center-edge angle (22/44). Anteroposterior (AP) pelvis plain radiographs were the most commonly used imaging modality (33 studies). Poor-quality evidence exists in support of most currently used radiographic markers, including the crossover sign, lateral center-edge angle, posterior wall sign, ischial spine sign, coxa profunda, acetabular protrusion, and acetabular index. There is poor-quality conflicting evidence regarding the use of the herniation pit to diagnose pincer-type FAI. Some novel measurements, such as β-angle, acetabular roof ratio, and acetabular retroversion index, have been proposed, but they also lack support from the literature. No strong evidence exists to support a single best set of current radiographic markers for the diagnosis of pincer-type FAI, largely due to the lack of better quality trials (levels 1 and 2) that compare conventional radiographic findings with the gold standard, which is the intraoperative findings. More sophisticated imaging modalities such as computed tomography and magnetic resonance arthrography are often needed to diagnose pincer-type FAI, and these investigations are relatively accurate in assessing labral pathology or cartilage damage.

Microsatellites for Oenothera gayleana and O. hartwegii subsp. filifolia (Onagraceae), and their utility in section Calylophus1

PubMed Central

Lewis, Emily M.; Fant, Jeremie B.; Moore, Michael J.; Hastings, Amy P.; Larson, Erica L.; Agrawal, Anurag A.; Skogen, Krissa A.

2016-01-01

Premise of the study: Eleven nuclear and four plastid microsatellite markers were screened for two gypsum endemic species, Oenothera gayleana and O. hartwegii subsp. filifolia, and tested for cross-amplification in the remaining 11 taxa within Oenothera sect. Calylophus (Onagraceae). Methods and Results: Microsatellite markers were tested in two to three populations spanning the ranges of both O. gayleana and O. hartwegii subsp. filifolia. The nuclear microsatellite loci consisted of both di- and trinucleotide repeats with one to 17 alleles per population. Several loci showed significant deviation from Hardy–Weinberg equilibrium, which may be evidence of chromosomal rings. The plastid microsatellite markers identified one to seven haplotypes per population. The transferability of these markers was confirmed in all 11 taxa within Oenothera sect. Calylophus. Conclusions: The microsatellite loci characterized here are the first developed and tested in Oenothera sect. Calylophus. These markers will be used to assess whether pollinator foraging distance influences population genetic parameters in predictable ways. PMID:26949578

Serum biochemical markers in lung cancer.

PubMed Central

Burt, R. W.; Ratcliffe, J. G.; Stack, B. H.; Cuthbert, J.; Kennedy, R. S.; Corker, C. S.; Franchimont, P.; Spilg, W. G.; Stimson, W. H.

1978-01-01

The prevalence of elevated serum levels of 5 potential tumour-associated antigens was determined in patients with lung cancer sampled at the time of initial presentation, using age- and sex-matched patients with benign lung disease as controls. Elevated levels (greater than upper 95th centile of controls) were found as follows: carcinoembryonic antigen (CEA), 17%; pregnancy-associated alpha-macroglobulin (PAM), 16%; casein 14%; human chorionic gonadotrophin (HCG) 6%; alpha-foetoprotein (AFP), 1.5%. The prevalence of elevated CEA levels (but not other markers) was higher in patients with evidence of extra-thoracic tumour spread (23%) mainly due to anaplastic tumours and adenocarcinomas. A degree of concordance of elevated marker levels occurred with CEA, HCG, casein and AFP, but there was a striking discordance of elevated CEA and PAM levels. Simultaneous assays of CEA and PAM will detect the majority of patients with elevations of any of the markers studied, and are likely to be the most useful biochemical markers in following the response of lung tumours to therapy. PMID:77672

Molecular evidence that the genes for dioecism and monoecism in Spinacia oleracea L. are located at different loci in a chromosomal region

PubMed Central

Yamamoto, K; Oda, Y; Haseda, A; Fujito, S; Mikami, T; Onodera, Y

2014-01-01

Spinach (Spinacia oleracea L.) is widely known to be dioecious. However, monoecious plants can also occur in this species. Sex expression in dioecious spinach plants is controlled by a single gene pair termed X and Y. Our previous study showed that a single, incompletely dominant gene, which controls the monoecious condition in spinach line 03–336, should be allelic or linked to X/Y. Here, we developed 19 AFLP markers closely linked to the monoecious gene. The AFLP markers were mapped to a 38.2-cM chromosomal region that included the monoecious gene, which is bracketed between flanking markers with a distance of 7.1 cM. The four AFLP markers developed in our studies were converted into sequence-characterized amplified region (SCAR) markers, which are linked to both the monoecious gene and Y and are common to both populations segregating for the genes. Linkage analysis using the SCAR markers suggested that the monoecious gene (M) and Y are located in different intervals, between different marker pairs. Analysis of populations segregating for both M and Y also directly demonstrates linkage of the genes at a distance of ∼12 cM. The data presented in this study may be useful for breeding dioecious and highly male monoecious lines utilized as the pollen parents for hybrid seed production, as well as for studies of the evolutionary history of sexual systems in this species, and can provide a molecular basis for positional cloning of the sex-determining genes. PMID:24169648

Emotion, Decision-Making and Substance Dependence: A Somatic-Marker Model of Addiction

PubMed Central

Verdejo-García, A; Pérez-García, M; Bechara, A

2006-01-01

Similar to patients with orbitofrontal cortex lesions, substance dependent individuals (SDI) show signs of impairments in decision-making, characterised by a tendency to choose the immediate reward at the expense of severe negative future consequences. The somatic-marker hypothesis proposes that decision-making depends in many important ways on neural substrates that regulate homeostasis, emotion and feeling. According to this model, there should be a link between abnormalities in experiencing emotions in SDI, and their severe impairments in decision-making in real-life. Growing evidence from neuroscientific studies suggests that core aspects of substance addiction may be explained in terms of abnormal emotional guidance of decision-making. Behavioural studies have revealed emotional processing and decision-making deficits in SDI. Combined neuropsychological and physiological assessment has demonstrated that the poorer decision-making of SDI is associated with altered reactions to reward and punishing events. Imaging studies have shown that impaired decision-making in addiction is associated with abnormal functioning of a distributed neural network critical for the processing of emotional information, including the ventromedial cortex, the amygdala, the striatum, the anterior cingulate cortex, and the insular/somato-sensory cortices, as well as non-specific neurotransmitter systems that modulate activities of neural processes involved in decision-making. The aim of this paper is to review this growing evidence, and to examine the extent of which these studies support a somatic-marker model of addiction. PMID:18615136

Covariance Association Test (CVAT) Identifies Genetic Markers Associated with Schizophrenia in Functionally Associated Biological Processes.

PubMed

Rohde, Palle Duun; Demontis, Ditte; Cuyabano, Beatriz Castro Dias; Børglum, Anders D; Sørensen, Peter

2016-08-01

Schizophrenia is a psychiatric disorder with large personal and social costs, and understanding the genetic etiology is important. Such knowledge can be obtained by testing the association between a disease phenotype and individual genetic markers; however, such single-marker methods have limited power to detect genetic markers with small effects. Instead, aggregating genetic markers based on biological information might increase the power to identify sets of genetic markers of etiological significance. Several set test methods have been proposed: Here we propose a new set test derived from genomic best linear unbiased prediction (GBLUP), the covariance association test (CVAT). We compared the performance of CVAT to other commonly used set tests. The comparison was conducted using a simulated study population having the same genetic parameters as for schizophrenia. We found that CVAT was among the top performers. When extending CVAT to utilize a mixture of SNP effects, we found an increase in power to detect the causal sets. Applying the methods to a Danish schizophrenia case-control data set, we found genomic evidence for association of schizophrenia with vitamin A metabolism and immunological responses, which previously have been implicated with schizophrenia based on experimental and observational studies. Copyright © 2016 by the Genetics Society of America.

Applications of Redwood Genotyping by Using Microsatellite Markers

Treesearch

Chris Brinegar; Dan Bruno; Ryan Kirkbride; Steven Glavas; Ingrid Udranszky

2007-01-01

A panel of polymorphic microsatellite markers have been developed in coast redwood (Sequoia sempervirens). Two loci in particular (Seq18D7-3 and Seq21E5) demonstrate the potential of microsatellite genotyping in the assessment of genetic diversity and inheritance in redwoods. The highly polymorphic Seq18D7-3 marker provided evidence for the planting...

Syntactic Fast Mapping: The Korean Extrinsic Plural Marker

ERIC Educational Resources Information Center

Kim, Chae-Eun; O'Grady, William; Deen, Kamil; Kim, Kitaek

2017-01-01

This article shows that the Korean Extrinsic Plural Marker (EPM) may be acquired by children on the basis of very little evidence. The EPM marks distributivity, unlike the Instrinsic Plural Marker, which marks plurality. Thirty monolingual learners of Korean aged 5;03 to 6;09 (mean age 6;01) were tested using a series of Truth Value Judgment Tasks…

Rapid quantification and sex determination of forensic evidence materials.

PubMed

Andréasson, Hanna; Allen, Marie

2003-11-01

DNA quantification of forensic evidence is very valuable for an optimal use of the available biological material. Moreover, sex determination is of great importance as additional information in criminal investigations as well as in identification of missing persons, no suspect cases, and ancient DNA studies. While routine forensic DNA analysis based on short tandem repeat markers includes a marker for sex determination, analysis of samples containing scarce amounts of DNA is often based on mitochondrial DNA, and sex determination is not performed. In order to allow quantification and simultaneous sex determination on minute amounts of DNA, an assay based on real-time PCR analysis of a marker within the human amelogenin gene has been developed. The sex determination is based on melting curve analysis, while an externally standardized kinetic analysis allows quantification of the nuclear DNA copy number in the sample. This real-time DNA quantification assay has proven to be highly sensitive, enabling quantification of single DNA copies. Although certain limitations were apparent, the system is a rapid, cost-effective, and flexible assay for analysis of forensic casework samples.

Inhibition of oxygen-glucose deprivation-induced apoptosis of human adipose-derived stem cells by genetic modification with antiapoptotic protein bcl-2.

PubMed

Cui, Ziwei; Shen, Liangyun; Lin, Yue; Wang, Shuqin; Zheng, Dongfeng; Tan, Qian

2014-08-01

Adipose-derived stem cells (ADSCs) have become a promising tool for a wide range of cell-based therapies. However, transplanted ADSCs do not survive well under ischemic conditions. In this study we aimed to inhibit oxygen-glucose deprivation (OGD)-induced apoptosis of human ADSCs by genetic modification with antiapoptotic protein Bcl-2. After isolation and culture, the phenotypes of human ADSCs at passage 3 were analyzed by flow cytometry. Then, genetic modification of ADSCs with Bcl-2 was carried out. Bcl-2 gene transfection was verified by Western blot analysis and multipotent differentiation properties were evaluated in Bcl-2-modified ADSCs (Bcl-2-ADSCs). Apoptosis was evaluated by a TUNEL assay under ischemic conditions induced by OGD. Apoptotic nuclei were also assessed and quantified by Hoechst staining. The cultured ADSCs expressed stem cell-associated markers CD29, CD34, CD44, and CD90, but not fibroblast marker HLA-DR or hematopoietic stem cell marker CD133. The Bcl-2 gene was transferred into ADSCs efficiently, and Bcl-2-ADSCs differentiated into adipocytes, chondrocytes, and osteoblasts. In addition, Bcl-2 overexpression reduced the percentage of apoptotic Bcl-2-ADSCs by 38 % under OGD. Our results indicate that Bcl-2 overexpression through gene transfection inhibits apoptosis of ADSCs under ischemic conditions. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Next generation DNA sequencing technology delivers valuable genetic markers for the genomic orphan legume species, Bituminaria bituminosa

PubMed Central

2011-01-01

Background Bituminaria bituminosa is a perennial legume species from the Canary Islands and Mediterranean region that has potential as a drought-tolerant pasture species and as a source of pharmaceutical compounds. Three botanical varieties have previously been identified in this species: albomarginata, bituminosa and crassiuscula. B. bituminosa can be considered a genomic 'orphan' species with very few genomic resources available. New DNA sequencing technologies provide an opportunity to develop high quality molecular markers for such orphan species. Results 432,306 mRNA molecules were sampled from a leaf transcriptome of a single B. bituminosa plant using Roche 454 pyrosequencing, resulting in an average read length of 345 bp (149.1 Mbp in total). Sequences were assembled into 3,838 isotigs/contigs representing putatively unique gene transcripts. Gene ontology descriptors were identified for 3,419 sequences. Raw sequence reads containing simple sequence repeat (SSR) motifs were identified, and 240 primer pairs flanking these motifs were designed. Of 87 primer pairs developed this way, 75 (86.2%) successfully amplified primarily single fragments by PCR. Fragment analysis using 20 primer pairs in 79 accessions of B. bituminosa detected 130 alleles at 21 SSR loci. Genetic diversity analyses confirmed that variation at these SSR loci accurately reflected known taxonomic relationships in original collections of B. bituminosa and provided additional evidence that a division of the botanical variety bituminosa into two according to geographical origin (Mediterranean region and Canary Islands) may be appropriate. Evidence of cross-pollination was also found between botanical varieties within a B. bituminosa breeding programme. Conclusions B. bituminosa can no longer be considered a genomic orphan species, having now a large (albeit incomplete) repertoire of expressed gene sequences that can serve as a resource for future genetic studies. This experimental approach was effective in developing codominant and polymorphic SSR markers for application in diverse genetic studies. These markers have already given new insight into genetic variation in B. bituminosa, providing evidence that a division of the botanical variety bituminosa may be appropriate. This approach is commended to those seeking to develop useful markers for genomic orphan species. PMID:22171578

Skin temperature and core-peripheral temperature gradient as markers of hemodynamic status in critically ill patients: a review.

PubMed

Schey, Bernadette M; Williams, David Y; Bucknall, Tracey

2010-01-01

To examine the evidential basis underpinning the monitoring of skin temperature and core-peripheral temperature gradient as elements of hemodynamic assessment in critically ill and adult cardiac surgical patients. Twenty-six studies examining the efficacy of skin temperature or temperature gradient as markers of hemodynamic status were selected as part of an integrative review. Evidence pertaining to the efficacy of these parameters as markers of cardiac function is equivocal and has not been well appraised in the adult cardiac surgical population. Skin temperature and systemic vascular resistance are also affected by factors other than cardiac output. Skin temperature and core-peripheral temperature gradient should not be considered in isolation from other hemodynamic parameters when assessing cardiac status until they are validated by further large-scale prospective studies. 2010. Published by Mosby, Inc.

Genetic Structure, Linkage Disequilibrium and Signature of Selection in Sorghum: Lessons from Physically Anchored DArT Markers

PubMed Central

Bouchet, Sophie; Pot, David; Deu, Monique; Rami, Jean-François; Billot, Claire; Perrier, Xavier; Rivallan, Ronan; Gardes, Laëtitia; Xia, Ling; Wenzl, Peter; Kilian, Andrzej; Glaszmann, Jean-Christophe

2012-01-01

Population structure, extent of linkage disequilibrium (LD) as well as signatures of selection were investigated in sorghum using a core sample representative of worldwide diversity. A total of 177 accessions were genotyped with 1122 informative physically anchored DArT markers. The properties of DArTs to describe sorghum genetic structure were compared to those of SSRs and of previously published RFLP markers. Model-based (STRUCTURE software) and Neighbor-Joining diversity analyses led to the identification of 6 groups and confirmed previous evolutionary hypotheses. Results were globally consistent between the different marker systems. However, DArTs appeared more robust in terms of data resolution and bayesian group assignment. Whole genome linkage disequilibrium as measured by mean r2 decreased from 0.18 (between 0 to 10 kb) to 0.03 (between 100 kb to 1 Mb), stabilizing at 0.03 after 1 Mb. Effects on LD estimations of sample size and genetic structure were tested using i. random sampling, ii. the Maximum Length SubTree algorithm (MLST), and iii. structure groups. Optimizing population composition by the MLST reduced the biases in small samples and seemed to be an efficient way of selecting samples to make the best use of LD as a genome mapping approach in structured populations. These results also suggested that more than 100,000 markers may be required to perform genome-wide association studies in collections covering worldwide sorghum diversity. Analysis of DArT markers differentiation between the identified genetic groups pointed out outlier loci potentially linked to genes controlling traits of interest, including disease resistance genes for which evidence of selection had already been reported. In addition, evidence of selection near a homologous locus of FAR1 concurred with sorghum phenotypic diversity for sensitivity to photoperiod. PMID:22428056

Genetic structure, linkage disequilibrium and signature of selection in Sorghum: lessons from physically anchored DArT markers.

PubMed

Bouchet, Sophie; Pot, David; Deu, Monique; Rami, Jean-François; Billot, Claire; Perrier, Xavier; Rivallan, Ronan; Gardes, Laëtitia; Xia, Ling; Wenzl, Peter; Kilian, Andrzej; Glaszmann, Jean-Christophe

2012-01-01

Population structure, extent of linkage disequilibrium (LD) as well as signatures of selection were investigated in sorghum using a core sample representative of worldwide diversity. A total of 177 accessions were genotyped with 1122 informative physically anchored DArT markers. The properties of DArTs to describe sorghum genetic structure were compared to those of SSRs and of previously published RFLP markers. Model-based (STRUCTURE software) and Neighbor-Joining diversity analyses led to the identification of 6 groups and confirmed previous evolutionary hypotheses. Results were globally consistent between the different marker systems. However, DArTs appeared more robust in terms of data resolution and bayesian group assignment. Whole genome linkage disequilibrium as measured by mean r(2) decreased from 0.18 (between 0 to 10 kb) to 0.03 (between 100 kb to 1 Mb), stabilizing at 0.03 after 1 Mb. Effects on LD estimations of sample size and genetic structure were tested using i. random sampling, ii. the Maximum Length SubTree algorithm (MLST), and iii. structure groups. Optimizing population composition by the MLST reduced the biases in small samples and seemed to be an efficient way of selecting samples to make the best use of LD as a genome mapping approach in structured populations. These results also suggested that more than 100,000 markers may be required to perform genome-wide association studies in collections covering worldwide sorghum diversity. Analysis of DArT markers differentiation between the identified genetic groups pointed out outlier loci potentially linked to genes controlling traits of interest, including disease resistance genes for which evidence of selection had already been reported. In addition, evidence of selection near a homologous locus of FAR1 concurred with sorghum phenotypic diversity for sensitivity to photoperiod.

Biologic and Computational Modeling of Mammographic Density and Stromal Patterning

DTIC Science & Technology

2009-07-01

research effort. INTRODUCTION: Mammographic density serves as independent marker of short term breast cancer risk and a surrogate marker of...response to a variety of prevention agents1-3. Although a majority of breast cancers are epithelial in origin, there is evidence that stromal content of...the breast is an important predictor or mammographic density. There is increasing evidence that the stroma plays a role in breast cancer initiation4

Feeling the Insight: Uncovering Somatic Markers of the "aha" Experience.

PubMed

Shen, Wangbing; Tong, Yu; Yuan, Yuan; Zhan, Huijia; Liu, Chang; Luo, Jing; Cai, Houde

2018-03-01

Whether internal insight can be recognized by experiencing (somatic feeling) remains an unexplored problem. This study investigated the issue by examining potential somatic markers of the "aha" experience occurring at the moment of sudden insight. Participants were required to solve a set of compound remote associates (CRA) problems and were simultaneously monitored via electrodermal and cardiovascular recordings. The "aha"-related psychological components and somatic markers were determined by contrasting insightful solutions with non-insightful solutions. Results showed that the "aha" experience was an amalgam entailing positive affects and approached cognition accompanied by a greater mean skin conductance response (mSCR) amplitude and a marginally accelerated heart rate than the "no-aha" one. These results confirm and extend findings of the multidimensionality of the "aha" feeling and offer the first direct evidence of somatic markers, particularly an electrodermal signature of an "aha" feeling, which suggests a sudden insight could likely be experienced by individuals' external soma.

Applicability of universal Bacteroidales genetic marker for microbial monitoring of drinking water sources in comparison to conventional indicators.

PubMed

Shahryari, A; Nikaeen, M; Khiadani Hajian, M; Nabavi, F; Hatamzadeh, M; Hassanzadeh, A

2014-11-01

Water quality monitoring is essential for the provision of safe drinking water. In this study, we compared a selection of fecal indicators with universal Bacteroidales genetic marker to identify fecal pollution of a variety of drinking water sources. A total of 60 samples were collected from water sources. The microbiological parameters included total coliforms, fecal coliforms, Escherichia coli and fecal streptococci as the fecal indicator bacteria (FIB), Clostridium perfringens and H2S bacteria as alternative indicators, universal Bacteroidales genetic marker as a promising alternative fecal indicator, and Salmonella spp., Shigella spp., and E. coli O157 as pathogenic bacteria. From 60 samples analyzed, Bacteroidales was the most frequently detected indicator followed by total coliforms. However, the Bacteroidales assay failed to detect the marker in nine samples positive for FIB and other alternative indicators. The results of our study showed that the absence of Bacteroidales is not necessarily an evidence of fecal and pathogenic bacteria absence and may be unable to ensure the safety of the water. Further research, however, is required for a better understanding of the use of a Bacteroidales genetic marker as an indicator in water quality monitoring programs.

Effects of weathering on biological marker and aromatic hydrocarbon composition of organic matter in Phosphoria shale outcrop

USGS Publications Warehouse

Clayton, J.L.; King, J.D.

1987-01-01

GC-MS analyses were performed on core samples collected from a shale outcrop of the Permian Phosphoria Formation in Utah, U.S.A., to study effects of weathering on selected biological marker and aromatic (phenanthrene) hydrocarbon compounds. Among the biological markers, the most important weathering effects are a decrease in the 20S 20R diastereomer ratio of the C29 steranes and loss of low molecular weight triaromatic steroids. A decrease in the C19 through C22 tricylcic terpanes occurs relative to the total C19-C26 tricyclic fraction. Pronounced loss of methyl-substituted phenanthrenes occurs relative to phenanthrene. No major effect on the overall distribution of pentacyclic terpanes is evident. ?? 1987.

Paternal leakage and heteroplasmy of mitochondrial genomes in Silene vulgaris: evidence from experimental crosses.

PubMed

Bentley, Kerin E; Mandel, Jennifer R; McCauley, David E

2010-07-01

The inheritance of mitochondrial genetic (mtDNA) markers in the gynodioecious plant Silene vulgaris was studied using a series of controlled crosses between parents of known mtDNA genotype followed by quantitative PCR assays of offspring genotype. Overall, approximately 2.5% of offspring derived from crosses between individuals that were homoplasmic for different mtDNA marker genotypes showed evidence of paternal leakage. When the source population of the pollen donor was considered, however, population-specific rates of leakage varied significantly around this value, ranging from 10.3% to zero. When leakage did occur, the paternal contribution ranged from 0.5% in some offspring (i.e., biparental inheritance resulting in a low level of heteroplasmy) to 100% in others. Crosses between mothers known to be heteroplasmic for one of the markers and homoplasmic fathers showed that once heteroplasmy enters a maternal lineage it is retained by approximately 17% of offspring in the next generation, but lost from the others. The results are discussed with regard to previous studies of heteroplasmy in open-pollinated natural populations of S. vulgaris and with regard to the potential impact of mitochondrial paternal leakage and heteroplasmy on both the evolution of the mitochondrial genome and the evolution of gynodioecy.

Cocoa Polyphenols and Inflammatory Markers of Cardiovascular Disease

PubMed Central

Khan, Nasiruddin; Khymenets, Olha; Urpí-Sardà, Mireia; Tulipani, Sara; Garcia-Aloy, Mar; Monagas, María; Mora-Cubillos, Ximena; Llorach, Rafael; Andres-Lacueva, Cristina

2014-01-01

Epidemiological studies have demonstrated the beneficial effect of plant-derived food intake in reducing the risk of cardiovascular disease (CVD). The potential bioactivity of cocoa and its polyphenolic components in modulating cardiovascular health is now being studied worldwide and continues to grow at a rapid pace. In fact, the high polyphenol content of cocoa is of particular interest from the nutritional and pharmacological viewpoints. Cocoa polyphenols are shown to possess a range of cardiovascular-protective properties, and can play a meaningful role through modulating different inflammatory markers involved in atherosclerosis. Accumulated evidence on related anti-inflammatory effects of cocoa polyphenols is summarized in the present review. PMID:24566441

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

Evidence for the free radical/oxidative stress theory of ageing from the CHANCES consortium: a meta-analysis of individual participant data.

PubMed

Schöttker, Ben; Brenner, Hermann; Jansen, Eugène H J M; Gardiner, Julian; Peasey, Anne; Kubínová, Růžena; Pająk, Andrzej; Topor-Madry, Roman; Tamosiunas, Abdonas; Saum, Kai-Uwe; Holleczek, Bernd; Pikhart, Hynek; Bobak, Martin

2015-12-15

The free radical/oxidative stress theory of ageing has received considerable attention, but the evidence on the association of oxidative stress markers with mortality is sparse. We measured derivatives of reactive oxygen metabolite (D-ROM) levels as a proxy for the reactive oxygen species concentration and total thiol levels (TTL) as a proxy for the redox control status in 10,622 men and women (age range, 45-85 years), from population-based cohorts from Germany, Poland, Czech Republic, and Lithuania, of whom 1,702 died during follow-up. Both oxidative stress markers were significantly associated with all-cause mortality independently from established risk factors (including inflammation) and from each other in all cohorts. Regarding cause-specific mortality, compared to low D-ROM levels (≤ 340 Carr U), very high D-ROM levels (>500 Carr U) were strongly associated with both cardiovascular (relative risk (RR), 5.09; 95 % CI, 2.67-9.69) and cancer mortality (RR, 4.34; 95 % CI, 2.31-8.16). TTL was only associated with CVD mortality (RR, 1.30; 95 % CI, 1.15-1.48, for one-standard-deviation-decrease). The strength of the association of TTL with CVD mortality increased with age of the participants (RR for one-standard-deviation-decrease in those aged 70-85 years was 1.65; 95 % CI, 1.22-2.24). In these four population-based cohort studies from Central and Eastern Europe, the oxidative stress serum markers D-ROM and TTL were independently and strongly associated with all-cause and CVD mortality. In addition, D-ROM levels were also strongly associated with cancer mortality. This study provides epidemiological evidence supporting the free radical/oxidative stress theory of ageing and suggests that d-ROMs and TTL are useful oxidative stress markers associated with premature mortality.

Change in urinary markers of osteoclast activity following palliative radiotherapy for bone metastases.

PubMed

Chow, E; Hird, A; Zhang, Liying; Sinclair, E; Danjoux, C; Barnes, E; Tsao, M; Barbera, L; Wong, Shun; Vieth, R

2009-05-01

To examine the effect of radiotherapy for bone metastases on urinary markers of osteoclast activity. Patients with radiological evidence of bone metastases planned for palliative radiotherapy were eligible for the study. A urine specimen was collected before and 1 month after radiotherapy to assess levels of calcium, creatinine, magnesium, phosphate, N-telopeptide and pyridinoline. The Brief Pain Inventory was completed in person at baseline and by telephone follow-up at 1 month after radiotherapy. Patients were classified as responders (complete or partial pain response) or non-responders (stable or progressive pain) to radiotherapy based on the International Bone Metastases Consensus Criteria for end point measurements. Absolute values of urine markers were compared between responders and non-responders, or between responders and patients with progression. Our study population consisted of 74 men and 51 women. A single 8 Gy or 20 Gy in five daily fractions were commonly employed. At the 1 month follow-up, all Brief Pain Inventory functional interference scores showed a highly significant decrease from baseline (P<0.01). From our study population, 58 (64%) were classified as responders and 57 (46%) as non-responders to radiotherapy. We compared the urinary markers between the responders and the non-responders. There were no statistically significant differences between the two groups either in terms of baseline markers or in terms of month 1 follow-up markers. There was no significant change from baseline to the 1 month follow-up in responders or in non-responders to radiotherapy. Baseline levels of urinary markers could not predict which patient would benefit from palliative radiotherapy.

Evaluation of InnoTyper® 21 in a sample of Rio de Janeiro population as an alternative forensic panel.

PubMed

Moura-Neto, R S; Mello, I C T; Silva, R; Maette, A P C; Bottino, C G; Woerner, A; King, J; Wendt, F; Budowle, B

2018-01-01

The use of bi-allelic markers such as retrotransposable element insertion polymorphisms or Innuls (for insertion/null) can overcome some limitations of short tandem repeat (STR) loci in typing forensic biological evidence. This study investigated the efficiency of the InnoTyper® 21 Innul markers in an urban admixed population sample in Rio de Janeiro (n = 40) and one highly compromised sample collected as evidence by the Rio de Janeiro police. No significant departures from Hardy-Weinberg equilibrium were detected after the Bonferroni correction (α' ≈ 0.05/20, p < 0.0025), and no significant linkage disequilibrium was observed between markers. Assuming loci independence, the cumulative random match probability (RMP) was 2.3 × 10 -8 . A lower mean Fis value was obtained for this sample population compared with those of three North American populations (African-American, Southwest Hispanic, US Caucasian). Principal component analysis with the three North American populations and one from 21 East Asian population showed that African Americans segregated as an independent group while US Caucasian, Southwest Hispanic, East Asian, and Rio de Janeiro populations are in a single large heterogeneous group. Also, a full Innuls profile was produced from an evidence sample, despite the DNA being highly degraded. In conclusion, this system is a useful complement to standard STR kits.

Basic mechanisms of urgency: preclinical and clinical evidence.

PubMed

Michel, Martin C; Chapple, Christopher R

2009-08-01

Urgency is the core symptom of the overactive bladder symptom complex, but the underlying mechanisms are not fully understood. To review clinical and experimental studies related to how bladder filling and urgency are sensed and what causes urgency and to discuss how this process affects potential therapeutic strategies. Review of published reports. The definition of urgency as a desire implies that it can only be assessed in cognitively intact patients and that animal studies have to rely on surrogate markers thereof, such as detrusor overactivity (DO); however, DO and urgency are not always associated. While the precise mechanisms of how urgency is sensed remain unclear, accumulating evidence suggests that they may differ from the physiologic sensation of bladder filling. Studies on the neurophysiology of urgency sensing are hampered by reliance on the surrogate marker DO. Functional brain imaging may help to understand the central neurophysiology, but, until now, it has not specifically focused on urgency. With regard to causes of urgency, multiple theories have been forwarded. While none of them has been proven, it should be noted that they are not mutually exclusive, and, in specific patients, different causes may be present. The development of improved therapeutic strategies against urgency will be helped by a better understanding of how urgency is perceived and the underlying causes. Rigorous use of existing definitions and the search for reliable surrogate markers will aid such attempts.

Substituting whole grains for refined grains in a 6-wk randomized trial has a modest effect on gut microbiota and immune and inflammatory markers of healthy adults

USDA-ARS?s Scientific Manuscript database

Background: Observational studies suggest an inverse association between whole-grain (WG) consumption and inflammation. However, evidence from interventional studies is limited, and few studies have included measurements of cell-mediated immunity. Objective: We assessed the effects of diets rich in ...

Evidence-Based Reading and Writing Assessment for Dyslexia in Adolescents and Young Adults

ERIC Educational Resources Information Center

Nielsen, Kathleen; Abbott, Robert; Griffin, Whitney; Lott, Joe; Raskind, Wendy; Berninger, Virginia W.

2016-01-01

The same working memory and reading and writing achievement phenotypes (behavioral markers of genetic variants) validated in prior research with younger children and older adults in a multi-generational family genetics study of dyslexia were used to study 81 adolescent and young adults (ages 16 to 25) from that study. Dyslexia is impaired word…

Behavioural biomarkers and mobile mental health: a new paradigm.

PubMed

Hidalgo-Mazzei, Diego; Young, Allan H; Vieta, Eduard; Colom, Francesc

2018-05-06

Over recent decades, the field of psychiatry has allocated a vast amount of resources and efforts to make available more accurate and objective methods to diagnose, assess and monitor treatment outcomes in psychiatric disorders. Despite the optimism and some significant progress in biological markers, it has become increasingly evident that they are failing to meet initial expectations due to their lack of specificity, inconsistent reliability and limited availability. On the other hand, there is an increasingly emerging evidence of mobile technologies' feasibility to measure mental illness activity. Moreover, taking into account its widespread use, availability and potential to capture behavioural markers, mobile-connected technologies could be strong candidates to fill and complement-at least at some degree-the gaps that biological markers couldn't. This represents an especially interesting opportunity to reform our current diagnostic system using a bottom-up research methodology based on digital and biological markers data instead of the classical traditional top-down approach. Therefore, the field might benefit of further exploring this promising -and increasingly evidence-based- pathway as well as other auspicious alternatives in order to attain a more holistic and integrative approach in research, which could ultimately impact real-world clinical practice.

Matrix metalloproteinases and educational attainment in refractive error: evidence of gene-environment interactions in the AREDS study

PubMed Central

Wojciechowski, Robert; Yee, Stephanie S.; Simpson, Claire L.; Bailey-Wilson, Joan E.; Stambolian, Dwight

2012-01-01

Purpose A previous study of Old Order Amish families has shown association of ocular refraction with markers proximal to matrix metalloproteinase (MMP) genes MMP1 and MMP10 and intragenic to MMP2. We conducted a candidate gene replication study of association between refraction and single nucleotide polymorphisms (SNPs) within these genomic regions. Design Candidate gene genetic association study. Participants 2,000 participants drawn from the Age Related Eye Disease Study (AREDS) were chosen for genotyping. After quality control filtering, 1912 individuals were available for analysis. Methods Microarray genotyping was performed using the HumanOmni 2.5 bead array. SNPs originally typed in the previous Amish association study were extracted for analysis. In addition, haplotype tagging SNPs were genotyped using TaqMan assays. Quantitative trait association analyses of mean spherical equivalent refraction (MSE) were performed on 30 markers using linear regression models and an additive genetic risk model, while adjusting for age, sex, education, and population substructure. Post-hoc analyses were performed after stratifying on a dichotomous education variable. Pointwise (P-emp) and multiple-test study-wise (P-multi) significance levels were calculated empirically through permutation. Main outcome measures MSE was used as a quantitative measure of ocular refraction. Results The mean age and ocular refraction were 68 years (SD=4.7) and +0.55 D (SD=2.14), respectively. Pointwise statistical significance was obtained for rs1939008 (P-emp=0.0326). No SNP attained statistical significance after correcting for multiple testing. In stratified analyses, multiple SNPs reached pointwise significance in the lower-education group: 2 of these were statistically significant after multiple testing correction. The two highest-ranking SNPs in Amish families (rs1939008 and rs9928731) showed pointwise P-emp<0.01 in the lower-education stratum of AREDS participants. Conclusions We show suggestive evidence of replication of an association signal for ocular refraction to a marker between MMP1 and MMP10. We also provide evidence of a gene-environment interaction between previously-reported markers and education on refractive error. Variants in MMP1- MMP10 and MMP2 regions appear to affect population variation in ocular refraction in environmental conditions less favorable for myopia development. PMID:23098370

Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema.

PubMed

Lassere, Marissa N; Johnson, Kent R; Boers, Maarten; Tugwell, Peter; Brooks, Peter; Simon, Lee; Strand, Vibeke; Conaghan, Philip G; Ostergaard, Mikkel; Maksymowych, Walter P; Landewe, Robert; Bresnihan, Barry; Tak, Paul-Peter; Wakefield, Richard; Mease, Philip; Bingham, Clifton O; Hughes, Michael; Altman, Doug; Buyse, Marc; Galbraith, Sally; Wells, George

2007-03-01

There are clear advantages to using biomarkers and surrogate endpoints, but concerns about clinical and statistical validity and systematic methods to evaluate these aspects hinder their efficient application. Our objective was to review the literature on biomarkers and surrogates to develop a hierarchical schema that systematically evaluates and ranks the surrogacy status of biomarkers and surrogates; and to obtain feedback from stakeholders. After a systematic search of Medline and Embase on biomarkers, surrogate (outcomes, endpoints, markers, indicators), intermediate endpoints, and leading indicators, a quantitative surrogate validation schema was developed and subsequently evaluated at a stakeholder workshop. The search identified several classification schema and definitions. Components of these were incorporated into a new quantitative surrogate validation level of evidence schema that evaluates biomarkers along 4 domains: Target, Study Design, Statistical Strength, and Penalties. Scores derived from 3 domains the Target that the marker is being substituted for, the Design of the (best) evidence, and the Statistical strength are additive. Penalties are then applied if there is serious counterevidence. A total score (0 to 15) determines the level of evidence, with Level 1 the strongest and Level 5 the weakest. It was proposed that the term "surrogate" be restricted to markers attaining Levels 1 or 2 only. Most stakeholders agreed that this operationalization of the National Institutes of Health definitions of biomarker, surrogate endpoint, and clinical endpoint was useful. Further development and application of this schema provides incentives and guidance for effective biomarker and surrogate endpoint research, and more efficient drug discovery, development, and approval.

Identification of metabolites, clinical chemistry markers and transcripts associated with hepatotoxicity.

PubMed

Buness, Andreas; Roth, Adrian; Herrmann, Annika; Schmitz, Oliver; Kamp, Hennicke; Busch, Kristina; Suter, Laura

2014-01-01

Early and accurate pre-clinical and clinical biomarkers of hepatotoxicity facilitate the drug development process and the safety monitoring in clinical studies. We selected eight known model compounds to be administered to male Wistar rats to identify biomarkers of drug induced liver injury (DILI) using transcriptomics, metabolite profiling (metabolomics) and conventional endpoints. We specifically explored early biomarkers in serum and liver tissue associated with histopathologically evident acute hepatotoxicity. A tailored data analysis strategy was implemented to better differentiate animals with no treatment-related findings in the liver from animals showing evident hepatotoxicity as assessed by histopathological analysis. From the large number of assessed parameters, our data analysis strategy allowed us to identify five metabolites in serum and five in liver tissue, 58 transcripts in liver tissue and seven clinical chemistry markers in serum that were significantly associated with acute hepatotoxicity. The identified markers comprised metabolites such as taurocholic acid and putrescine (measured as sum parameter together with agmatine), classical clinical chemistry markers like AST (aspartate aminotransferase), ALT (alanine aminotransferase), and bilirubin, as well as gene transcripts like Igfbp1 (insulin-like growth factor-binding protein 1) and Egr1 (early growth response protein 1). The response pattern of the identified biomarkers was concordant across all types of parameters and sample matrices. Our results suggest that a combination of several of these biomarkers could significantly improve the robustness and accuracy of an early diagnosis of hepatotoxicity.

[Construction of genetic linkage map and localization of NBS-LRR like resistance gene analogues in cauliflower (Brassica oleracea var. botrytis)].

PubMed

Gu, Yu; Zhao, Qian-Cheng; Sun, De-Ling; Song, Wen-Qin

2007-06-01

Nucleotide binding site (NBS) profiling, a new method was used to map resistance gene analogues (RGAs) in cauliflower (Brassica oleracea var. botrytis). This method allows amplification and the mapping of genetic markers anchored in the conserved NBS encoding domain of plant disease resistance genes. AFLP was also performed to construct the cauliflower intervarietal genetic map. The aim of constructing genetic map was to identify potential molecular markers linked to important agronomic traits that would be particularly useful for development and improving the species. Using 17 AFLP primer combinations and two degeneration primer/enzyme combinations, a total of 234 AFLP markers and 21 NBS markers were mapped in the F2 population derived from self-pollinating a single F1 plant of the cross AD White Flower x C-8. The markers were mapped in 9 of major linkage groups spanning 668.4 cM, with an average distance of 2.9 cM between adjacent mapped markers. The AFLP markers were well distributed throughout the linkage groups. The linkage groups contained from 12 to 47 loci each and the distance between two consecutive loci ranged from 0 to 14.9 cM. NBS markers were mapped on 8 of the 9 linkage groups of the genetic map. Most of these markers were organized in clusters. This result demonstrates the feasibility of the NBS-profiling method for generating NBS markers for resistance loci in cauliflower. The clustering of the markers mapped in this study adds to the evidence that most of them could be real RGAs.

Marker-dependent associations among oxidative stress, growth and survival during early life in a wild mammal

PubMed Central

Selman, Colin; Blount, Jonathan D.; Pilkington, Jill G.; Watt, Kathryn A.; Pemberton, Josephine M.; Reid, Jane M.

2016-01-01

Oxidative stress (OS) is hypothesized to be a key physiological mechanism mediating life-history trade-offs, but evidence from wild populations experiencing natural environmental variation is limited. We tested the hypotheses that increased early life growth rate increases OS, and that increased OS reduces first-winter survival, in wild Soay sheep (Ovis aries) lambs. We measured growth rate and first-winter survival for four consecutive cohorts, and measured two markers of oxidative damage (malondialdehyde (MDA), protein carbonyls (PC)) and two markers of antioxidant (AOX) protection (total AOX capacity (TAC), superoxide dismutase (SOD)) from blood samples. Faster lamb growth was weakly associated with increased MDA, but not associated with variation in the other three markers. Lambs with higher SOD activity were more likely to survive their first winter, as were male but not female lambs with lower PC concentrations. Survival did not vary with MDA or total TAC. Key predictions relating OS to growth and survival were therefore supported in some OS markers, but not others. This suggests that different markers capture different aspects of the complex relationships between individual oxidative state, physiology and fitness, and that overarching hypotheses relating OS to life-history variation cannot be supported or refuted by studying individual markers. PMID:27733545

Lifestyle impacts on the aging associated expression of biomarkers of DNA damage and telomere dysfunction in human blood

PubMed Central

Song, Zhangfa; von Figura, Guido; Liu, Yan; Kraus, Johann M.; Torrice, Chad; Dillon, Patric; Rudolph-Watabe, Masami; Ju, Zhenyu; Kestler, Hans A.; Sanoff, Hanna; Rudolph, K. Lenhard

2010-01-01

Summary Cellular aging is characterised by telomere shortening, which can lead to uncapping of chromosome ends (telomere dysfunction) and that activation of DNA damage responses. There is some evidence the DNA damage accumulates during human aging and that lifestyle factors contribute to the accumulation of DNA damage. Recent studies have identified a set of serum markers that are induced by telomere dysfunction and DNA damage and these markers showed an increased expression in blood during human aging. Here, we investigated the influence of lifestyle factors (such as exercise, smoking, body mass) on the aging associated expression of serum markers of DNA damage (CRAMP, EF-1α, Stathmin, n-acetyl-glucosaminidase, and chitinase) in comparison to other described markers of cellular aging (p16INK4a upregulation and telomere shortening) in human peripheral blood. The study shows that lifestyle factors have an age-independent impact on the expression level of biomarkers of DNA damage. Smoking and increased body mass indices were associated with elevated levels of biomarkers of DNA damage independent of the age of the individuals. In contrast, exercise was associated with an age-independent reduction in the expression of biomarkers of DNA damage in human blood. The expression of biomarkers of DNA damage correlated positively with p16INK4a expression and negatively with telomere length in peripheral blood T-lymphocytes. Together, these data provide experimental evidence that both aging and lifestyle impact on the accumulation of DNA damage during human aging. PMID:20560902

Evolution of the tRNALeu (UAA) Intron and Congruence of Genetic Markers in Lichen-Symbiotic Nostoc

PubMed Central

Kaasalainen, Ulla; Olsson, Sanna; Rikkinen, Jouko

2015-01-01

The group I intron interrupting the tRNALeu UAA gene (trnL) is present in most cyanobacterial genomes as well as in the plastids of many eukaryotic algae and all green plants. In lichen symbiotic Nostoc, the P6b stem-loop of trnL intron always involves one of two different repeat motifs, either Class I or Class II, both with unresolved evolutionary histories. Here we attempt to resolve the complex evolution of the two different trnL P6b region types. Our analysis indicates that the Class II repeat motif most likely appeared first and that independent and unidirectional shifts to the Class I motif have since taken place repeatedly. In addition, we compare our results with those obtained with other genetic markers and find strong evidence of recombination in the 16S rRNA gene, a marker widely used in phylogenetic studies on Bacteria. The congruence of the different genetic markers is successfully evaluated with the recently published software Saguaro, which has not previously been utilized in comparable studies. PMID:26098760

Evolution of the tRNALeu (UAA) Intron and Congruence of Genetic Markers in Lichen-Symbiotic Nostoc.

PubMed

Kaasalainen, Ulla; Olsson, Sanna; Rikkinen, Jouko

2015-01-01

The group I intron interrupting the tRNALeu UAA gene (trnL) is present in most cyanobacterial genomes as well as in the plastids of many eukaryotic algae and all green plants. In lichen symbiotic Nostoc, the P6b stem-loop of trnL intron always involves one of two different repeat motifs, either Class I or Class II, both with unresolved evolutionary histories. Here we attempt to resolve the complex evolution of the two different trnL P6b region types. Our analysis indicates that the Class II repeat motif most likely appeared first and that independent and unidirectional shifts to the Class I motif have since taken place repeatedly. In addition, we compare our results with those obtained with other genetic markers and find strong evidence of recombination in the 16S rRNA gene, a marker widely used in phylogenetic studies on Bacteria. The congruence of the different genetic markers is successfully evaluated with the recently published software Saguaro, which has not previously been utilized in comparable studies.

[Human reproduction and environmental risk factors].

PubMed

Petrelli, G; Mantovani, A; Menditto, A

1999-01-01

Environmental pollution is a great cause of concern, in particular, growing attention is being paid to the potential of many chemicals to affect the reproductive system in humans. The key role of prevention and control of reproductive hazards is recognized world-wide. Many chemicals have been shown to impair fertility and/or prenatal and perinatal development in experimental studies. However, a sufficient evidence of an effect on human reproduction is available for some compounds only. The use of biological markers may improve the assessment of exposure to chemicals, contribute to identify mechanisms of action and put into evidence early, reversible, biological effects. Valid biological markers are also needed in epidemiological studies: without reliable data on the level of current and past exposures it is difficult to establish a causal relationship between a pollutant and the occurrence of adverse health effects. A multidisciplinary approach to risk assessment is required. Priorities for interdisciplinary research on environmental chemicals and reproduction include the identification of susceptible population subgroups and risk assessment of exposure to multiple chemicals.

Identification of the origin of faecal contamination in estuarine oysters using Bacteroidales and F-specific RNA bacteriophage markers.

PubMed

Mieszkin, S; Caprais, M P; Le Mennec, C; Le Goff, M; Edge, T A; Gourmelon, M

2013-09-01

The aim of this study was to identify the origin of faecal pollution impacting the Elorn estuary (Brittany, France) by applying microbial source tracking (MST) markers in both oysters and estuarine waters. The MST markers used were as follows: (i) human-, ruminant- and pig-associated Bacteroidales markers by real-time PCR and (ii) human genogroup II and animal genogroup I of F-specific RNA bacteriophages (FRNAPH) by culture/genotyping and by direct real-time reverse-transcriptase PCR. The higher occurrence of the human genogroup II of F-specific RNA bacteriophages using a culture/genotyping method, and human-associated Bacteroidales marker by real-time PCR, allowed the identification of human faecal contamination as the predominant source of contamination in oysters (total of 18 oyster batches tested) and waters (total of 24 water samples tested). The importance of using the intravalvular liquids instead of digestive tissues, when applying host-associated Bacteroidales markers in oysters, was also revealed. This study has shown that the application of a MST toolbox of diverse bacterial and viral methods can provide multiple lines of evidence to identify the predominant source of faecal contamination in shellfish from an estuarine environment. Application of this MST toolbox is a useful approach to understand the origin of faecal contamination in shellfish harvesting areas in an estuarine setting. © 2013 The Society for Applied Microbiology.

Localization of multiple neurotransmitters in surgically derived specimens of human atrial ganglia.

PubMed

Hoover, D B; Isaacs, E R; Jacques, F; Hoard, J L; Pagé, P; Armour, J A

2009-12-15

Dysfunction of the intrinsic cardiac nervous system is implicated in the genesis of atrial and ventricular arrhythmias. While this system has been studied extensively in animal models, far less is known about the intrinsic cardiac nervous system of humans. This study was initiated to anatomically identify neurotransmitters associated with the right atrial ganglionated plexus (RAGP) of the human heart. Biopsies of epicardial fat containing a portion of the RAGP were collected from eight patients during cardiothoracic surgery and processed for immunofluorescent detection of specific neuronal markers. Colocalization of markers was evaluated by confocal microscopy. Most intrinsic cardiac neuronal somata displayed immunoreactivity for the cholinergic marker choline acetyltransferase and the nitrergic marker neuronal nitric oxide synthase. A subpopulation of intrinsic cardiac neurons also stained for noradrenergic markers. While most intrinsic cardiac neurons received cholinergic innervation evident as punctate immunostaining for the high affinity choline transporter, some lacked cholinergic inputs. Moreover, peptidergic, nitrergic, and noradrenergic nerves provided substantial innervation of intrinsic cardiac ganglia. These findings demonstrate that the human RAGP has a complex neurochemical anatomy, which includes the presence of a dual cholinergic/nitrergic phenotype for most of its neurons, the presence of noradrenergic markers in a subpopulation of neurons, and innervation by a host of neurochemically distinct nerves. The putative role of multiple neurotransmitters in controlling intrinsic cardiac neurons and mediating efferent signaling to the heart indicates the possibility of novel therapeutic targets for arrhythmia prevention.

Against the Role of Inflammatory Markers in Renal Cell Carcinoma Prognosis: The Missing Link Between Evidence of Association and Clinical Applicability.

PubMed

Larcher, Alessandro; Dell'Oglio, Paolo; Salonia, Andrea; Capitanio, Umberto

2016-10-01

Although an association between inflammatory markers (IMs) and renal cell carcinoma (RCC) prognosis has been proven, how to translate such information into treatment strategy has not been determined. The strongest argument against the use of IMs in the management of patients diagnosed with RCC is the missing link between evidence of association and clinical applicability. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Intimate Partner Violence perpetration and cardiovascular risk: A systematic review.

PubMed

O'Neil, Adrienne; Scovelle, Anna J

2018-06-01

Intimate Partner Violence (IPV) perpetration may induce cardiovascular reactivity and risk markers thereby precipitating early onset cardiovascular disease (CVD). However, this relationship has been largely under-researched in comparison to the health impacts of IPV victimisation. We therefore aimed to systematically review the current evidence investigating the relationship between IPV perpetration and CV risk. Six databases (CINAHL, Ovid MEDLINE, Pubmed, Scopus, ProQuest, Google Scholar) were searched between August 2016 and August 2017 using a predefined search strategy. Inclusion criteria were studies of cross sectional and longitudinal design published since 2010, presenting IPV status by perpetrators (as distinct from victims) and an outcome of CVD (e.g. cardiac disease, stroke), CV risk markers (e.g. blood pressure) and/or a composite CV risk score. Twenty two potentially eligible studies were identified and full texts recovered. After ineligible studies were excluded, four remained (total n = 10,665). Positive relationships were observed between IPV perpetration and (i) short term CV reactivity markers (higher heart rate, lower vagal ratios, shorter pre-ejection periods) and (ii) longer term CV risk factors and outcomes including greater systolic blood pressure, incident hypertension, elevated 30 year CV risk score and self-report cardiac disease. Despite being a neglected area of research characterised by a high degree of heterogeneity, the early evidence suggests that IPV perpetration may be associated with elevated risk of CVD. We discuss these findings in the context of CVD prevention from the individual, family and inter-generational perspectives and directions for future studies.

Depth profiling of marker layers using x-ray waveguide structures

NASA Astrophysics Data System (ADS)

Gupta, Ajay; Rajput, Parasmani; Saraiya, Amit; Reddy, V. R.; Gupta, Mukul; Bernstorff, Sigrid; Amenitsch, H.

2005-08-01

It is demonstrated that x-ray waveguide structures can be used for depth profiling of a marker layer inside the guiding layer with an accuracy of better than 0.2 nm. A combination of x-ray fluorescence and x-ray reflectivity measurements can provide detailed information about the structure of the guiding layer. The position and thickness of the marker layer affect different aspects of the angle-dependent x-ray fluorescence pattern, thus making it possible to determine the structure of the marker layer in an unambiguous manner. As an example, effects of swift heavy ion irradiation on a Si/M/Si trilayer ( M=Fe , W), forming the cavity of the waveguide structure, have been studied. It is found that in accordance with the prediction of thermal spike model, Fe is much more sensitive to swift heavy ion induced modifications as compared to W, even in thin film form. However, a clear evidence of movement of the Fe marker layer towards the surface is observed after irradiation, which cannot be understood in terms of the thermal spike model alone.

Gene-Based Testing of Interactions in Association Studies of Quantitative Traits

PubMed Central

Ma, Li; Clark, Andrew G.; Keinan, Alon

2013-01-01

Various methods have been developed for identifying gene–gene interactions in genome-wide association studies (GWAS). However, most methods focus on individual markers as the testing unit, and the large number of such tests drastically erodes statistical power. In this study, we propose novel interaction tests of quantitative traits that are gene-based and that confer advantage in both statistical power and biological interpretation. The framework of gene-based gene–gene interaction (GGG) tests combine marker-based interaction tests between all pairs of markers in two genes to produce a gene-level test for interaction between the two. The tests are based on an analytical formula we derive for the correlation between marker-based interaction tests due to linkage disequilibrium. We propose four GGG tests that extend the following P value combining methods: minimum P value, extended Simes procedure, truncated tail strength, and truncated P value product. Extensive simulations point to correct type I error rates of all tests and show that the two truncated tests are more powerful than the other tests in cases of markers involved in the underlying interaction not being directly genotyped and in cases of multiple underlying interactions. We applied our tests to pairs of genes that exhibit a protein–protein interaction to test for gene-level interactions underlying lipid levels using genotype data from the Atherosclerosis Risk in Communities study. We identified five novel interactions that are not evident from marker-based interaction testing and successfully replicated one of these interactions, between SMAD3 and NEDD9, in an independent sample from the Multi-Ethnic Study of Atherosclerosis. We conclude that our GGG tests show improved power to identify gene-level interactions in existing, as well as emerging, association studies. PMID:23468652

Interpersonal discrimination and markers of adiposity in longitudinal studies: a systematic review.

PubMed

Bernardo, C de O; Bastos, J L; González-Chica, D A; Peres, M A; Paradies, Y C

2017-09-01

While the impact of interpersonal discrimination on mental health is well established, its effects on physical health outcomes have not been fully elucidated. This study systematically reviewed the literature on the prospective association between interpersonal discrimination and markers of adiposity. Medline, Web of Science, Scopus, PsycInfo, SciELO, LILACS, Google Scholar, Capes/Brazil and ProQuest databases were used to retrieve relevant information in November 2016. The results from the 10 studies that met the inclusion criteria support an association between interpersonal self-reported discrimination and the outcomes. In general, the most consistent findings were for weight and body mass index (BMI) among women, i.e. high levels of self-reported discrimination were related to increased weight and BMI. Waist circumference (WC) showed a similar pattern of association with discrimination, in a positive direction, but an inverted U-shaped association was also found. Despite a few inverse associations between discrimination and markers of adiposity, none of the associations were statistically significant. Overall, markers of adiposity were consistently associated with discrimination, mainly through direct and nonlinear associations. This review provides evidence that self-reported discrimination can play an important role in weight, BMI and WC changes. © 2017 World Obesity Federation.

A systematic review of the asymmetric inheritance of cellular organelles in eukaryotes: A critique of basic science validity and imprecision

PubMed Central

Collins, Anne; Ross, Janine

2017-01-01

We performed a systematic review to identify all original publications describing the asymmetric inheritance of cellular organelles in normal animal eukaryotic cells and to critique the validity and imprecision of the evidence. Searches were performed in Embase, MEDLINE and Pubmed up to November 2015. Screening of titles, abstracts and full papers was performed by two independent reviewers. Data extraction and validity were performed by one reviewer and checked by a second reviewer. Study quality was assessed using the SYRCLE risk of bias tool, for animal studies and by developing validity tools for the experimental model, organelle markers and imprecision. A narrative data synthesis was performed. We identified 31 studies (34 publications) of the asymmetric inheritance of organelles after mitotic or meiotic division. Studies for the asymmetric inheritance of centrosomes (n = 9); endosomes (n = 6), P granules (n = 4), the midbody (n = 3), mitochondria (n = 3), proteosomes (n = 2), spectrosomes (n = 2), cilia (n = 2) and endoplasmic reticulum (n = 2) were identified. Asymmetry was defined and quantified by variable methods. Assessment of the statistical reliability of the results indicated only two studies (7%) were judged to have low concern, the majority of studies (77%) were 'unclear' and five (16%) were judged to have 'high concerns'; the main reasons were low technical repeats (<10). Assessment of model validity indicated that the majority of studies (61%) were judged to be valid, ten studies (32%) were unclear and two studies (7%) were judged to have 'high concerns'; both described 'stem cells' without providing experimental evidence to confirm this (pluripotency and self-renewal). Assessment of marker validity indicated that no studies had low concern, most studies were unclear (96.5%), indicating there were insufficient details to judge if the markers were appropriate. One study had high concern for marker validity due to the contradictory results of two markers for the same organelle. For most studies the validity and imprecision of results could not be confirmed. In particular, data were limited due to a lack of reporting of interassay variability, sample size calculations, controls and functional validation of organelle markers. An evaluation of 16 systematic reviews containing cell assays found that only 50% reported adherence to PRISMA or ARRIVE reporting guidelines and 38% reported a formal risk of bias assessment. 44% of the reviews did not consider how relevant or valid the models were to the research question. 75% reviews did not consider how valid the markers were. 69% of reviews did not consider the impact of the statistical reliability of the results. Future systematic reviews in basic or preclinical research should ensure the rigorous reporting of the statistical reliability of the results in addition to the validity of the methods. Increased awareness of the importance of reporting guidelines and validation tools is needed for the scientific community. PMID:28562636

Cytogenetics of small cell carcinoma of the lung.

PubMed

Wurster-Hill, D H; Cannizzaro, L A; Pettengill, O S; Sorenson, G D; Cate, C C; Maurer, L H

1984-12-01

Nineteen cell lines derived from various malignant tissues of 15 patients with small cell carcinoma of the lung (SCCL) have been studied. The results showed heterogeneity in all cell lines, with no one consistent abnormality among them. Cell lines from 11 of the patients had minute and double minute chromosomes, and cell lines from 2 patients had abnormally banding regions, designated as ABRs, as distinguished from homogeneously staining regions (HSRs). The latter 2 and several of the former cell lines were derived from specimens taken before the patients were placed on therapy. All but 2 of the cell lines had a constant marker load, consisting of 24%-35% of the complement. Some markers remained stable through months and years of culture life, while other markers came and went. Chromosomes #1, #6 and #11 were most frequently involved in marker formation in the cell lines, and these were compared to similar markers in direct bone marrow preparations. Chromosome #1 markers were of variable structure, whereas #6 and #11 most often took the form of 6q- and 11p+ markers, with breakpoints most frequently at 6q23-25 and 11p11-12. A 3p- marker was found in a minority of cell lines. All of these markers were also found in direct marrow preparations from some patients with SCCL. Nonmonoclonal tumors arose from inoculation of bimodal cell lines into nude mice, but population selection by undetermined mechanism was evident. Cytogenetic parameters showed no positive correlation with hormone production by these cell lines.

INNULs: A novel design amplification strategy for retrotransposable elements for studying population variation.

PubMed

LaRue, Bobby L; Sinha, Sudhir K; Montgomery, Anne H; Thompson, Robyn; Klaskala, Lauren; Ge, Jianye; King, Jonathan; Turnbough, Meredith; Budowle, Bruce

2012-01-01

Retrotransposable elements (REs), consisting of long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), are a group of markers that can be useful for human identity testing. Until now, however, due to the inherent size difference (up to 6 kb in some instances) associated with insertion and null alleles (or INNULs), the use of REs for facilitated population studies has not been sought or practical. The size of the insertion elements (from a few hundred to several thousand bp) has proven to limit their utility as a marker because of the inefficient amplicon yield with PCR. A novel primer design now facilitates INNUL marker testing. A preliminary panel of single-locus markers was developed to evaluate the potential of typing these insertion elements. Nine INNULs (5 Alu and 4 LINEs) were typed in three major North American populations and analyzed for population genetic features. In addition, the variation of each marker among the sample populations provides insight of its potential use as individual identification or ancestral marker. INNUL markers were developed into fluorescently labeled single-loci PCR. Nine markers were developed with amplicons that were less than 180 bp in length, and, depending on the locus amplicons of the INNULs, alleles varied in size from 50 to 1 bp. This allele size is noteworthy because the insertion alleles of the 9 loci range in size from 297 to 6,195 bp. The allele distribution of the INNULs was assessed and analyzed in three major North American populations. Upon observation of the distribution of the alleles in three major North American populations, the markers generally met Hardy-Weinberg expectations, and there was little evidence of detectable levels of linkage disequilibrium. Due to varying distributions of the alleles in the major population groups tested, some of the markers might be better suited for use as an individual identification marker, while others are better suited for bio-ancestral studies. Using the primer design strategy described in our work, SINEs and (for the first time, to our knowledge) LINEs can be utilized as markers for studying population genetic variation that is more amenable to the limitations of the PCR technique. This study lays the foundation for future work of developing a multiplex panel of INNUL markers that can be used as a single-tube assay for human identity testing utilizing small amplicons (<180 bp), which could be useful for ancient or degraded forensic DNA samples. Copyright © 2012 S. Karger AG, Basel.

Cell surface marker profiling of human tracheal basal cells reveals distinct subpopulations, identifies MST1/MSP as a mitogenic signal, and identifies new biomarkers for lung squamous cell carcinomas.

PubMed

Van de Laar, Emily; Clifford, Monica; Hasenoeder, Stefan; Kim, Bo Ram; Wang, Dennis; Lee, Sharon; Paterson, Josh; Vu, Nancy M; Waddell, Thomas K; Keshavjee, Shaf; Tsao, Ming-Sound; Ailles, Laurie; Moghal, Nadeem

2014-12-31

The large airways of the lungs (trachea and bronchi) are lined with a pseudostratified mucociliary epithelium, which is maintained by stem cells/progenitors within the basal cell compartment. Alterations in basal cell behavior can contribute to large airway diseases including squamous cell carcinomas (SQCCs). Basal cells have traditionally been thought of as a uniform population defined by basolateral position, cuboidal cell shape, and expression of pan-basal cell lineage markers like KRT5 and TP63. While some evidence suggests that basal cells are not all functionally equivalent, few heterogeneously expressed markers have been identified to purify and study subpopulations. In addition, few signaling pathways have been identified that regulate their cell behavior. The goals of this work were to investigate tracheal basal cell diversity and to identify new signaling pathways that regulate basal cell behavior. We used flow cytometry (FACS) to profile cell surface marker expression at a single cell level in primary human tracheal basal cell cultures that maintain stem cell/progenitor activity. FACS results were validated with tissue staining, in silico comparisons with normal basal cell and lung cancer datasets, and an in vitro proliferation assay. We identified 105 surface markers, with 47 markers identifying potential subpopulations. These subpopulations generally fell into more (~ > 13%) or less abundant (~ < 6%) groups. Microarray gene expression profiling supported the heterogeneous expression of these markers in the total population, and immunostaining of large airway tissue suggested that some of these markers are relevant in vivo. 24 markers were enriched in lung SQCCs relative to adenocarcinomas, with four markers having prognostic significance in SQCCs. We also identified 33 signaling receptors, including the MST1R/RON growth factor receptor, whose ligand MST1/MSP was mitogenic for basal cells. This work provides the largest description to date of molecular diversity among human large airway basal cells. Furthermore, these markers can be used to further study basal cell function in repair and disease, and may aid in the classification and study of SQCCs.

Predictors of emotional distress a year or more after diagnosis of cancer: A systematic review of the literature.

PubMed

Cook, Sharon A; Salmon, Peter; Hayes, Gemma; Byrne, Angela; Fisher, Peter L

2018-03-01

Why some people recover emotionally after diagnosis and treatment of cancer and others do not is poorly understood. To identify factors around the time of diagnosis that predict longer-term distress is a necessary step in developing interventions to reduce patients' vulnerability. This review identified the demographic, clinical, social, and psychological factors available at or within 3 months of diagnosis that are reliable predictors of emotional distress at least 12 months later. A systematic search of literature for prospective studies addressing our research question and predicting a range of distress outcomes was conducted. Thirty-nine papers (reporting 36 studies) were subjected to narrative synthesis of the evidence. There was no consistent evidence that demographic, clinical, or social factors reliably predicted longer-term distress. Of the psychological factors examined, only baseline distress (significant in 26 of 30 relevant papers; 24 of 28 studies) and neuroticism (significant in all 5 papers/studies that examined it) consistently predicted longer-term distress. The heterogeneity of included studies, particularly in populations studied and methodology, precluded meta-analytic techniques. This review supports current clinical guidance advising early assessment of distress as a marker of vulnerability to persistent problems. Additionally, neuroticism is also indicated as a useful marker of vulnerability. However, the review also highlights that more sophisticated research designs, capable of identifying the psychological processes that underlie the association between these marker variables and persistent distress, are needed before more effective early interventions can be developed. © 2018 The Authors. Psycho-Oncology Published by John Wiley & Sons Ltd.

Argument Structure Use in Monolingual and Bilingual Children

ERIC Educational Resources Information Center

Souto, Sofia M.

2013-01-01

The data on language acquisition in children with specific language impairment (SLI) primarily come from studies in English reporting particular morphemes that differentiate them from their typically developing (TYP) peers, but markers of impairment vary cross-linguistically. There is some cross-linguistic evidence that SLI disrupts language…

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.

Soy foods: are they useful for optimal bone health?

PubMed Central

2011-01-01

Numerous studies have investigated the relationship between soy foods, soy protein, or isoflavone extracts and markers of bone health and osteoporosis prevention, and have come to conflicting conclusions. Research on dietary patterns, rather than on specific food ingredients or individual foods, may offer an opportunity for better understanding the role of soy foods in bone health. Evidence is reviewed regarding the question of whether soy foods contribute to a dietary pattern in humans that supports and promotes bone health. Soy foods are associated with improved markers of bone health and improved outcomes, especially among Asian women. Although the optimal amounts and types of soy foods needed to support bone health are not yet clear, dietary pattern evidence suggests that regular consumption of soy foods is likely to be useful for optimal bone health as an integral part of a dietary pattern that is built largely from whole plant foods. PMID:22870487

Soy foods: are they useful for optimal bone health?

PubMed

Lanou, Amy J

2011-12-01

Numerous studies have investigated the relationship between soy foods, soy protein, or isoflavone extracts and markers of bone health and osteoporosis prevention, and have come to conflicting conclusions. Research on dietary patterns, rather than on specific food ingredients or individual foods, may offer an opportunity for better understanding the role of soy foods in bone health. Evidence is reviewed regarding the question of whether soy foods contribute to a dietary pattern in humans that supports and promotes bone health. Soy foods are associated with improved markers of bone health and improved outcomes, especially among Asian women. Although the optimal amounts and types of soy foods needed to support bone health are not yet clear, dietary pattern evidence suggests that regular consumption of soy foods is likely to be useful for optimal bone health as an integral part of a dietary pattern that is built largely from whole plant foods.

[Effort-reward imbalance at work and depression: current research evidence].

PubMed

Siegrist, J

2013-01-01

In view of highly prevalent stressful conditions in modern working life, in particular increasing work pressure and job insecurity, it is of interest to know whether specific constellations of an adverse psychosocial work environment increase the risk of depressive disorder among employed people. This contribution gives a short overview of current research evidence based on an internationally established work stress model of effort-reward imbalance. Taken together, results from seven prospective epidemiological investigations demonstrate a two-fold elevated relative risk of incident depressive disorder over a mean observation period of 2.7 years among exposed versus non-exposed employees. Additional findings from experimental and quasi-experimental studies point to robust associations of effort-reward imbalance at work with proinflammatory cytokines and markers of reduced immune competence. These latter markers may indicate potential psychobiological pathways. In conclusion, incorporating this new knowledge into medical treatment and preventive efforts seems well justified.

Inheritance mode of microsatellite loci and their use for kinship analysis in the Pacific oyster ( Crassostrea gigas)

NASA Astrophysics Data System (ADS)

Li, Qi; Zheng, Xiaodong; Yu, Ruihai

2008-08-01

Five full-sib families of the Pacific oyster ( Crassostrea gigas) larvae were used to study the mode of inheritance at eight microsatellite loci, and the feasibility of these markers for kinship estimate was also examined. All eight microsatellite loci were compatible with Mendelian inheritance. Neither evidence of sex-linked barriers to transmission nor evidence of major barriers to fertilization between gametes from the parents was shown. Three of the eight loci showed the presence of null alleles in four families, demonstrating the need to conduct comprehensive species-specific inheritance studies for microsatellite loci used in population genetic studies. Although the null allele heterozygotes were considered as homozygotes in the calculation of genetic distance, offspring from five full-sib families were unambiguously discriminated in the neighbor-joining dendrogram. This result indicates that the microsatellite markers may be capable of discriminating between related and unrelated oyster larvae in the absence of pedigree information, and is applicable to the investigation of the effective number of parents contributing to the hatchery population of the Pacific oyster.

Reduced energy availability: implications for bone health in physically active populations.

PubMed

Papageorgiou, Maria; Dolan, Eimear; Elliott-Sale, Kirsty J; Sale, Craig

2018-04-01

The present review critically evaluates existing literature on the effects of short- and long-term low energy availability (EA) on bone metabolism and health in physically active individuals. We reviewed the literature on the short-term effects of low EA on markers of bone metabolism and the long-term effects of low EA on outcomes relating to bone health (bone mass, microarchitecture and strength, bone metabolic markers and stress fracture injury risk) in physically active individuals. Available evidence indicates that short-term low EA may increase markers of bone resorption and decrease markers of bone formation in physically active women. Bone metabolic marker responses to low EA are less well known in physically active men. Cross-sectional studies investigating the effects of long-term low EA suggest that physically active individuals who have low EA present with lower bone mass, altered bone metabolism (favouring bone resorption), reduced bone strength and increased risk for stress fracture injuries. Reduced EA has a negative influence on bone in both the short- and long-term, and every effort should be made to reduce its occurrence in physically active individuals. Future interventions are needed to explore the effects of long-term reduced EA on bone health outcomes, while short-term low EA studies are also required to give insight into the pathophysiology of bone alterations.

Highly Proficient Bilinguals Implement Inhibition: Evidence from N-2 Language Repetition Costs

ERIC Educational Resources Information Center

Declerck, Mathieu; Thoma, Aniella M.; Koch, Iring; Philipp, Andrea M.

2015-01-01

Several, but not all, models of language control assume that highly proficient bilinguals implement little to no inhibition during bilingual language production. In the current study, we tested this assumption with a less equivocal marker of inhibition (i.e., n-2 language repetition costs) than previous language switching studies have. N-2…

Inflammatory Markers in the Staging of Bipolar Disorder: A Systematic Review of the Literature.

PubMed

Castaño-Ramírez, Oscar Mauricio; Sepúlveda-Arias, Juan C; Duica, Kelly; Díaz Zuluaga, Ana M; Vargas, Cristian; López-Jaramillo, Carlos

Previous studies suggest that inflammatory molecules play an important role in the pathophysiology of Bipolar Disorder (BD). The evidence suggests that BD may present a progressive course. Therefore there are theories that postulate the relationship between progression and stages of the disease with distinct peripheral biomarkers. The aim of this study was to carry out a systematic review of the literature of studies about the association between peripheral inflammatory markers and clinical variables related with staging in BD patients. We conducted a systematic review using electronic databases: PubMed, SciELO, LiLACS and PsycINFO. Keywords were divided into inflammatory markers and, BD and staging. Studies involving euthymic BD patients, studies evaluating peripheral biomarkers and studies correlating these with clinical variables related to neuroprogression or stage of BD were included. We present and discuss the methods and findings of ten articles. The inflammatory markers were measured with different techniques and show some contradictories results. The TNF superfamily and inflammatory cytokines may have a relationship with the neuroprogression of the disease. This study suggests that TNF and ILs could play a role in neuroprogression. However, longitudinal studies are needed to clarify the relationship between factors associated with neuroprogression. Copyright © 2017 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Evidence for paternal leakage in hybrid periodical cicadas (Hemiptera: Magicicada spp.).

PubMed

Fontaine, Kathryn M; Cooley, John R; Simon, Chris

2007-09-12

Mitochondrial inheritance is generally assumed to be maternal. However, there is increasing evidence of exceptions to this rule, especially in hybrid crosses. In these cases, mitochondria are also inherited paternally, so "paternal leakage" of mitochondria occurs. It is important to understand these exceptions better, since they potentially complicate or invalidate studies that make use of mitochondrial markers. We surveyed F1 offspring of experimental hybrid crosses of the 17-year periodical cicadas Magicicada septendecim, M. septendecula, and M. cassini for the presence of paternal mitochondrial markers at various times during development (1-day eggs; 3-, 6-, 9-week eggs; 16-month old 1st and 2nd instar nymphs). We found evidence of paternal leakage in both reciprocal hybrid crosses in all of these samples. The relative difficulty of detecting paternal mtDNA in the youngest eggs and ease of detecting leakage in older eggs and in nymphs suggests that paternal mitochondria proliferate as the eggs develop. Our data support recent theoretical predictions that paternal leakage may be more common than previously estimated.

Evidence for Paternal Leakage in Hybrid Periodical Cicadas (Hemiptera: Magicicada spp.)

PubMed Central

Fontaine, Kathryn M.; Cooley, John R.; Simon, Chris

2007-01-01

Mitochondrial inheritance is generally assumed to be maternal. However, there is increasing evidence of exceptions to this rule, especially in hybrid crosses. In these cases, mitochondria are also inherited paternally, so “paternal leakage” of mitochondria occurs. It is important to understand these exceptions better, since they potentially complicate or invalidate studies that make use of mitochondrial markers. We surveyed F1 offspring of experimental hybrid crosses of the 17-year periodical cicadas Magicicada septendecim, M. septendecula, and M. cassini for the presence of paternal mitochondrial markers at various times during development (1-day eggs; 3-, 6-, 9-week eggs; 16-month old 1st and 2nd instar nymphs). We found evidence of paternal leakage in both reciprocal hybrid crosses in all of these samples. The relative difficulty of detecting paternal mtDNA in the youngest eggs and ease of detecting leakage in older eggs and in nymphs suggests that paternal mitochondria proliferate as the eggs develop. Our data support recent theoretical predictions that paternal leakage may be more common than previously estimated. PMID:17849021

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).

Physiological markers of motor inhibition during human behavior

PubMed Central

Duque, Julie; Greenhouse, Ian; Labruna, Ludovica; Ivry, Richard B.

2017-01-01

Transcranial magnetic stimulation (TMS) studies in humans have shown that many behaviors engage processes that suppress excitability within the corticospinal tract. Inhibition of the motor output pathway has been extensively studied in the context of action stopping, where a planned movement needs to be abruptly aborted. Recent TMS work has also revealed markers of motor inhibition during the preparation of movement. Here, we review the evidence for motor inhibition during action stopping and action preparation, focusing on studies that have used TMS to monitor changes in the excitability of the corticospinal pathway. We discuss how these physiological results have motivated theoretical models of how the brain selects actions, regulates movement initiation and execution, and switches from one state to another. PMID:28341235

Endothelin-3 production by human rhabdomyosarcoma: a possible new marker with a paracrine role.

PubMed

Palladini, Arianna; Astolfi, Annalisa; Croci, Stefania; De Giovanni, Carla; Nicoletti, Giordano; Rosolen, Angelo; Sartori, Francesca; Lollini, Pier-Luigi; Landuzzi, Lorena; Nanni, Patrizia

2006-03-01

Several autocrine and paracrine growth factor circuits have been found in human rhabdomyosarcoma cells. In this study we show that endothelin-3 (ET-3), a vasoactive peptide, is produced by human rhabdomyosarcoma cell lines, whereas it is not expressed by human sarcoma cell lines of non-muscle origin. We did not find evidence of a significant autocrine loop; nevertheless ET-3 produced by rhabdomyosarcoma cells can act as a paracrine factor, since it promotes migration of endothelial cells. Moreover ET-3 is present in plasma of mice bearing xenografts of human rhabdomyosarcoma cells, and may be potential new marker of the human rhabdomyosarcoma to be studied further.

Development of 11 polymorphic microsatellite markers for the blackberry rust fungus Phragmidium violaceum

USDA-ARS?s Scientific Manuscript database

Eleven polymorphic microsatellite markers were developed for the Uredinales fungus Phragmidium violaceum, which causes leaf rust on European blackberry (Rubus fruticosus L. aggregate). Allele frequency ranged between two and seventeen alleles per locus with no evidence of linkage disequilibrium amon...

Transcription factor GATA-4 is a marker of anaplasia in adrenocortical neoplasms of the domestic ferret (Mustela putorius furo).

PubMed

Peterson, R A; Kiupel, M; Bielinska, M; Kiiveri, S; Heikinheimo, M; Capen, C C; Wilson, D B

2004-07-01

Adrenocortical neoplasms are a common cause of morbidity in neutered ferrets. Recently we showed that gonadectomized DBA/2J mice develop adrenocortical tumors that express transcription factor GATA-4. Therefore, we screened archival specimens of adrenocortical neoplasms from neutered ferrets to determine whether GATA-4 could be used as a tumor marker in this species. Nuclear immunoreactivity for GATA-4 was evident in 19/22 (86%) of ferret adrenocortical carcinomas and was prominent in areas exhibiting myxoid differentiation. Normal adrenocortical cells lacked GATA-4 expression. Two other markers of adrenocortical tumors in gonadectomized mice, inhibin-alpha and luteinizing hormone receptor, were coexpressed with GATA-4 in some of the ferret tumors. No GATA-4 expression was observed in three cases of nodular hyperplasia, but patches of anaplastic cells expressing GATA-4 were evident in 7/14 (50%) of tumors classified as adenomas. We conclude that GATA-4 can function as a marker of anaplasia in ferret adrenocortical tumors.

C-reactive protein as a predictor of disease in smokers and former smokers: a review

PubMed Central

Tonstad, S; Cowan, J L

2009-01-01

Background: Cigarette smoking is a classical and a major risk factor in the development of several diseases with an inflammatory component, including cardiovascular disease and chronic obstructive pulmonary disease. Improvements in assays for protein markers of inflammation have led to many studies on these factors and their roles in disease. Aims: C-reactive protein (CRP) is one such marker and this review focuses on the evidence for using CRP as a diagnostic marker and how levels of this protein are modified according to the smoking status of the patient, both in terms of the current amount of cigarettes smoked and how CRP levels change following smoking cessation. Conclusions: Assay of CRP levels may be useful in monitoring disease progression and determining risk of future cardiovascular complications. However, as this marker is also an indicator of acute inflammation and challenges to the immune system, some caution must be exercised in interpreting the available data on CRP levels in patients with different chronic comorbidities. PMID:19732183

Chloroplast microsatellite markers for Artocarpus (Moraceae) developed from transcriptome sequences1

PubMed Central

Gardner, Elliot M.; Laricchia, Kristen M.; Murphy, Matthew; Ragone, Diane; Scheffler, Brian E.; Simpson, Sheron; Williams, Evelyn W.; Zerega, Nyree J. C.

2015-01-01

Premise of the study: Chloroplast microsatellite loci were characterized from transcriptomes of Artocarpus altilis (breadfruit) and A. camansi (breadnut). They were tested in A. odoratissimus (terap) and A. altilis and evaluated in silico for two congeners. Methods and Results: Fifteen simple sequence repeats (SSRs) were identified in chloroplast sequences from four Artocarpus transcriptome assemblies. The markers were evaluated using capillary electrophoresis in A. odoratissimus (105 accessions) and A. altilis (73). They were also evaluated in silico in A. altilis (10), A. camansi (6), and A. altilis × A. mariannensis (7) transcriptomes. All loci were polymorphic in at least one species, with all 15 polymorphic in A. camansi. Per species, average alleles per locus ranged between 2.2 and 2.5. Three loci had evidence of fragment-length homoplasy. Conclusions: These markers will complement existing nuclear markers by enabling confident identification of maternal and clone lines, which are often important in vegetatively propagated crops such as breadfruit. PMID:26421253

The use of isoniazid as a marker to monitor the self-administration of medicaments.

PubMed Central

Stark, J E; Ellard, G A; Gammon, P T; Fox, W

1975-01-01

1. Isoniazid was used as a marker to monitor the regularity of drug self-administration in a trial of chemoprophylaxis against natural influenza infection. Two hundred and sixty-two volunteers were treated for five weeks with a synthetic isoquinoline compound (U.K. 2371) or a matching placebo. 2. Five marker tablets containing isoniazid (150 mg) were incorporated into each regimen and their ingestion monitored by testing for acetylisoniazid in the urine. 3. Positive evidence of marker tablet consumption was obtained on 75% of the occasions on which urine samples were requested. The results obtained among the volunteers from each treatment group who returned urine specimens as requested (92%) indicated that they had swallowed at least 81% of their prescribed tablets. 4. The findings of the study suggest that when used in this way isoniazid is a very suitable compound for use on a few occasions for monitoring the self-administration of drugs in clinical trials. PMID:788733

Prioritizing molecular markers to test for in the initial workup of advanced non-small cell lung cancer: wants versus needs.

PubMed

West, Howard

2017-09-01

The current standard of care for molecular marker testing in patients with advanced non-small cell lung cancer (NSCLC) has been evolving over several years and is a product of the quality of the evidence supporting a targeted therapy for a specific molecular marker, the pre-test probability of that marker in the population, and the magnitude of benefit seen with that treatment. Among the markers that have one or more matched targeted therapies, only a few are in the subset for which they should be considered as most clearly worthy of prioritizing to detect in the first line setting in order to have them supplant other first line alternatives, and in only a subset of patients, as defined currently by NSCLC histology. Specifically, this currently includes testing for an activating epidermal growth factor receptor ( EGFR ) mutation or an anaplastic lymphoma kinase ( ALK ) or ROS1 rearrangement. This article reviews the history and data supporting the prioritization of these markers in patients with non-squamous NSCLC, a histologically selected population in whom the probability of these markers combined with the anticipated efficacy of targeted therapies against them is high enough to favor these treatments in the first line setting. In reviewing the evidence supporting this very limited core subset of most valuable molecular markers to detect in the initial workup of such patients, we can also see the criteria by which other actionable markers need to reach in order to be widely recognized as reliably valuable enough to warrant prioritization to detect in the initial workup of advanced NSCLC as well.

Using case-control designs for genome-wide screening for associations between genetic markers and disease susceptibility loci.

PubMed

Yang, Q; Khoury, M J; Atkinson, M; Sun, F; Cheng, R; Flanders, W D

1999-01-01

We used a case-control design to scan the genome for any associations between genetic markers and disease susceptibility loci using the first two replicates of the Mycenaean population from the GAW11 (Problem 2) data. Using a case-control approach, we constructed a series of 2-by-3 tables for each allele of every marker on all six chromosomes. Odds ratios (ORs) and 95% confidence intervals (95% CI) were estimated for all alleles of every marker. We selected the one allele for which the estimated OR had the minimum p-value to plot in the graph. Among these selected ORs, we calculated 95% CI for those that had a p-value < or = adjusted alpha level. Significantly high ORs were taken to indicate an association between a marker locus and a suspected disease-susceptibility gene. For the Mycenaean population, the case-control design identified allele number 1 of marker 24 on chromosome 1 to be associated with a disease susceptibility gene, OR = 2.10 (95% CI 1.66-2.62). Our approach failed to show any other significant association between case-control status and genetic markers. Stratified analysis on the environmental risk factor (E1) provided no further evidence of significant association other than allele 1 of marker 24 on chromosome 1. These data indicate the absence of linkage disequilibrium for markers flanking loci A, B, and C. Finally, we examined the effect of gene x environment (G x E) interaction for the identified allele. Our results provided no evidence of G x E interaction, but suggested that the environmental exposure alone was a risk factor for the disease.

Sewage pollution in urban stormwater runoff as evident from the widespread presence of multiple microbial and chemical source tracking markers.

PubMed

Sidhu, J P S; Ahmed, W; Gernjak, W; Aryal, R; McCarthy, D; Palmer, A; Kolotelo, P; Toze, S

2013-10-01

The concurrence of human sewage contamination in urban stormwater runoff (n=23) from six urban catchments across Australia was assessed by using both microbial source tracking (MST) and chemical source tracking (CST) markers. Out of 23 stormwater samples human adenovirus (HAv), human polyomavirus (HPv) and the sewage-associated markers; Methanobrevibacter smithii nifH and Bacteroides HF183 were detected in 91%, 56%, 43% and 96% of samples, respectively. Similarly, CST markers paracetamol (87%), salicylic acid (78%) acesulfame (96%) and caffeine (91%) were frequently detected. Twenty one samples (91%) were positive for six to eight sewage related MST and CST markers and remaining two samples were positive for five and four markers, respectively. A very good consensus (>91%) observed between the concurrence of the HF183, HAv, acesulfame and caffeine suggests good predictability of the presence of HAv in samples positive for one of the three markers. High prevalence of HAv (91%) also suggests that other enteric viruses may also be present in the stormwater samples which may pose significant health risks. This study underscores the benefits of employing a set of MST and CST markers which could include monitoring for HF183, adenovirus, caffeine and paracetamol to accurately detect human sewage contamination along with credible information on the presence of human enteric viruses, which could be used for more reliable public health risk assessments. Based on the results obtained in this study, it is recommended that some degree of treatment of captured stormwater would be required if it were to be used for non-potable purposes. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Molecular analysis of neocortical layer structure in the ferret

PubMed Central

Rowell, Joanna J.; Mallik, Atul K.; Dugas-Ford, Jennifer; Ragsdale, Clifton W.

2010-01-01

Molecular markers that distinguish specific layers of rodent neocortex are increasingly employed to study cortical development and the physiology of cortical circuits. The extent to which these markers represent general features of neocortical cell type identity across mammals is, however, unknown. To assess the conservation of layer markers more broadly, we isolated orthologs for fifteen layer-enriched genes in the ferret, a carnivore with a large, gyrencephalic brain, and analyzed their patterns of neocortical gene expression. Our major findings are: (1) Many but not all layer markers tested show similar patterns of layer-specific gene expression between mouse and ferret cortex, supporting the view that layer-specific cell type identity is conserved at a molecular level across mammalian superorders; (2) Our panel of deep layer markers (ER81/ETV1, SULF2, PCP4, FEZF2/ZNF312, CACNA1H, KCNN2/SK2, SYT6, FOXP2, CTGF) provides molecular evidence that the specific stratifications of layer 5 and 6 into 5a, 5b, 6a and 6b are also conserved between rodents and carnivores. (3) Variations in layer-specific gene expression are more pronounced across areas of ferret cortex than between homologous areas of mouse and ferret cortex; (4) This variation of area gene expression was clearest with the superficial layer markers studied (SERPINE2, MDGA1, CUX1, UNC5D, RORB/NR1F2, EAG2/KCNH5). Most dramatically, the layer 4 markers RORB and EAG2 disclosed a molecular sublamination to ferret visual cortex and demonstrated a molecular dissociation among the so-called agranular areas of the neocortex. Our findings establish molecular markers as a powerful complement to cytoarchitecture for neocortical layer and cell-type comparisons across mammals. PMID:20575059

The role of serum non-cholesterol sterols as surrogate markers of absolute cholesterol synthesis and absorption.

PubMed

Miettinen, T A; Gylling, H; Nissinen, M J

2011-10-01

To study the whole-body cholesterol metabolism in man, cholesterol synthesis and absorption need to be measured. Because of the complicated methods of the measurements, new approaches were developed including the analysis of serum non-cholesterol sterols. In current lipidologic papers and even in intervention studies, serum non-cholesterol sterols are frequently used as surrogate markers of cholesterol metabolism without any validation to the absolute metabolic variables. The present review compares serum non-cholesterol sterols with absolute measurements of cholesterol synthesis and absorption in published papers to find out whether the serum markers are valid indicators of cholesterol metabolism in various conditions. During statin treatment, during interventions of dietary fat, and in type 2 diabetes the relative and absolute variables of cholesterol synthesis and absorption were frequently but not constantly correlated with each other. In some occasions, especially in subjects with apolipoprotein E3/4 and E4/4 phenotypes, the relative metabolic markers were even more sensitive than the absolute ones to reflect changes in cholesterol metabolism during dietary interventions. Even in general population at very high absorption the homeostasis of cholesterol metabolism is disturbed damaging the validity of the serum markers. It is worth using several instead of only one precursor and absorption sterol marker for making conclusions of altered synthesis or absorption of cholesterol, and even then the presence of at least some absolute measurement is valuable. During consumption of plant sterol-enriched diets and in situations of interfered cholesterol homeostasis the relative markers do not adequately reflect cholesterol metabolism. Accordingly, the validity of the relative markers of cholesterol metabolism should not be considered as self-evident. Copyright © 2011 Elsevier B.V. All rights reserved.

Molecular analysis of neocortical layer structure in the ferret.

PubMed

Rowell, Joanna J; Mallik, Atul K; Dugas-Ford, Jennifer; Ragsdale, Clifton W

2010-08-15

Molecular markers that distinguish specific layers of rodent neocortex are increasingly employed to study cortical development and the physiology of cortical circuits. The extent to which these markers represent general features of neocortical cell type identity across mammals, however, is unknown. To assess the conservation of layer markers more broadly, we isolated orthologs for 15 layer-enriched genes in the ferret, a carnivore with a large, gyrencephalic brain, and analyzed their patterns of neocortical gene expression. Our major findings are: 1) Many but not all layer markers tested show similar patterns of layer-specific gene expression between mouse and ferret cortex, supporting the view that layer-specific cell type identity is conserved at a molecular level across mammalian superorders; 2) Our panel of deep layer markers (ER81/ETV1, SULF2, PCP4, FEZF2/ZNF312, CACNA1H, KCNN2/SK2, SYT6, FOXP2, CTGF) provides molecular evidence that the specific stratifications of layers 5 and 6 into 5a, 5b, 6a, and 6b are also conserved between rodents and carnivores; 3) Variations in layer-specific gene expression are more pronounced across areas of ferret cortex than between homologous areas of mouse and ferret cortex; 4) This variation of area gene expression was clearest with the superficial layer markers studied (SERPINE2, MDGA1, CUX1, UNC5D, RORB/NR1F2, EAG2/KCNH5). Most dramatically, the layer 4 markers RORB and EAG2 disclosed a molecular sublamination to ferret visual cortex and demonstrated a molecular dissociation among the so-called agranular areas of the neocortex. Our findings establish molecular markers as a powerful complement to cytoarchitecture for neocortical layer and cell-type comparisons across mammals. (c) 2010 Wiley-Liss, Inc.

The association of genome-wide significant spirometric loci with chronic obstructive pulmonary disease susceptibility.

PubMed

Castaldi, Peter J; Cho, Michael H; Litonjua, Augusto A; Bakke, Per; Gulsvik, Amund; Lomas, David A; Anderson, Wayne; Beaty, Terri H; Hokanson, John E; Crapo, James D; Laird, Nan; Silverman, Edwin K

2011-12-01

Two recent metaanalyses of genome-wide association studies conducted by the CHARGE and SpiroMeta consortia identified novel loci yielding evidence of association at or near genome-wide significance (GWS) with FEV(1) and FEV(1)/FVC. We hypothesized that a subset of these markers would also be associated with chronic obstructive pulmonary disease (COPD) susceptibility. Thirty-two single-nucleotide polymorphisms (SNPs) in or near 17 genes in 11 previously identified GWS spirometric genomic regions were tested for association with COPD status in four COPD case-control study samples (NETT/NAS, the Norway case-control study, ECLIPSE, and the first 1,000 subjects in COPDGene; total sample size, 3,456 cases and 1,906 controls). In addition to testing the 32 spirometric GWS SNPs, we tested a dense panel of imputed HapMap2 SNP markers from the 17 genes located near the 32 GWS SNPs and in a set of 21 well studied COPD candidate genes. Of the previously identified GWS spirometric genomic regions, three loci harbored SNPs associated with COPD susceptibility at a 5% false discovery rate: the 4q24 locus including FLJ20184/INTS12/GSTCD/NPNT, the 6p21 locus including AGER and PPT2, and the 5q33 locus including ADAM19. In conclusion, markers previously associated at or near GWS with spirometric measures were tested for association with COPD status in data from four COPD case-control studies, and three loci showed evidence of association with COPD susceptibility at a 5% false discovery rate.

Interaction between IRF6 and TGFA Genes Contribute to the Risk of Nonsyndromic Cleft Lip/Palate

PubMed Central

Letra, Ariadne; Fakhouri, Walid; Fonseca, Renata F.; Menezes, Renato; Kempa, Inga; Prasad, Joanne L.; McHenry, Toby G.; Lidral, Andrew C.; Moreno, Lina; Murray, Jeffrey C.; Daack-Hirsch, Sandra; Marazita, Mary L.; Castilla, Eduardo E.; Lace, Baiba; Orioli, Ieda M.; Granjeiro, Jose M.; Schutte, Brian C.; Vieira, Alexandre R.

2012-01-01

Previous evidence from tooth agenesis studies suggested IRF6 and TGFA interact. Since tooth agenesis is commonly found in individuals with cleft lip/palate (CL/P), we used four large cohorts to evaluate if IRF6 and TGFA interaction contributes to CL/P. Markers within and flanking IRF6 and TGFA genes were tested using Taqman or SYBR green chemistries for case-control analyses in 1,000 Brazilian individuals. We looked for evidence of gene-gene interaction between IRF6 and TGFA by testing if markers associated with CL/P were overtransmitted together in the case-control Brazilian dataset and in the additional family datasets. Genotypes for an additional 142 case-parent trios from South America drawn from the Latin American Collaborative Study of Congenital Malformations (ECLAMC), 154 cases from Latvia, and 8,717 individuals from several cohorts were available for replication of tests for interaction. Tgfa and Irf6 expression at critical stages during palatogenesis was analyzed in wild type and Irf6 knockout mice. Markers in and near IRF6 and TGFA were associated with CL/P in the Brazilian cohort (p<10−6). IRF6 was also associated with cleft palate (CP) with impaction of permanent teeth (p<10−6). Statistical evidence of interaction between IRF6 and TGFA was found in all data sets (p = 0.013 for Brazilians; p = 0.046 for ECLAMC; p = 10−6 for Latvians, and p = 0.003 for the 8,717 individuals). Tgfa was not expressed in the palatal tissues of Irf6 knockout mice. IRF6 and TGFA contribute to subsets of CL/P with specific dental anomalies. Moreover, this potential IRF6-TGFA interaction may account for as much as 1% to 10% of CL/P cases. The Irf6-knockout model further supports the evidence of IRF6-TGFA interaction found in humans. PMID:23029012

Borderline Personality Disorder and Emotion Regulation: Insights from the Polyvagal Theory

ERIC Educational Resources Information Center

Austin, Marilyn A.; Riniolo, Todd C.; Porges, Stephen W.

2007-01-01

The current study provides the first published evidence that the parasympathetic component of the autonomic nervous system differentiates the response profiles between individuals diagnosed with borderline personality disorder (BPD) and controls. Respiratory sinus arrhythmia (RSA), a non-invasive marker of the influence of the myelinated vagal…

Potential for Metabolomics-Based Markers of Exposure:Encouraging Evidence from Studies using Model Organisms

EPA Science Inventory

Genomic techniques (transcriptomics, proteomics, and metabolomics) have the potential to significantly improve the way chemical risk is managed in the 21st century. Indeed, a significant amount of research has been devoted to the use of these techniques to screen chemicals for h...

A cautionary note on the evaluation of genetic evidence from uniparentally transmitted markers.

PubMed

Amorim, António

2008-09-01

The combination of the information obtained from lineage genetic markers, such as mitochondrial DNA (mtDNA) and the non-homologous region of Y-chromosome, with data resulting from meiotically recombining loci (diploid/autosomal or haplodiploid/X chromosome) into a single likelihood ratio has been recently proposed. In this work we challenge this proposal and demonstrate that while the genetic evidence obtained from loci which reshuffle at meiosis is appropriate for individual probability calculations, mtDNA and Y-chromosome data are not and, consequently, that joining the evidential value of the two types of markers is generally inconsistent and should be avoided. The assumption of non-involvement of relatives must be clearly and explicitly stated and its acceptance must be left to the court decision.

Report from the Maryland epidemiology schizophrenia linkage study: No evidence for linkage between schizophrenia and a number of candidate and other genomic regions using a complex dominant model

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

Karayiorgou, M.; Hwang, J.; Elango, R.

Our collaborative group has undertaken a linkage study of schizophrenia, using a systematic sample of patients admitted to Maryland hospitals. An initial sample of 39 families, each having two or more affecteds, was available for genotyping candidate genes, candidate regions, and highly polymorphic markers randomly distributed throughout the genome. We used a single complex dominant model (with a disease gene frequency of 0.005 and age-dependent penetrance for affected phenotype: for under 35, penetrance = .45; for 35 and older, penetrance = .85). We report here 130 markers which met the exclusion criteria of LOD score < -2.00 at theta >more » 0.01 in at least 10 informative families, and no evidence for heterogeneity. We also report here markers that were tested as candidates for linkage to the schizophrenic phenotype. They were selected based on the following criteria: (a) proximity to reported chromosomal rearrangements (both 5q and 11q), (b) suggestions of linkage from other families (5q), or (c) presence of a candidate gene (5q, 11q, 3q: dopamine receptors 1, 2, and 3, respectively). We also tested for mutations of codon 717 in exon 17 of the amyloid precursor protein (APP) gene and were unable to detect the C to T substitution in our schizophrenic group. 48 refs., 2 tabs.« less

Food and plant bioactives for reducing cardiometabolic disease risk: an evidence based approach.

PubMed

Cicero, Arrigo F G; Fogacci, Federica; Colletti, Alessandro

2017-06-21

Cardiovascular diseases (CVDs) are one of the major causes of mortality and disability in Western countries. Prevention is known to be the cornerstone to lessen the incidence of CVDs and also to reduce the economic burden of both the citizen and the healthcare system. "Interventional medicine" certainly puts lifestyle modification as the first therapeutic step, including a healthy diet and physical activity. Secondly, a large body of research individuated a number of food and plant bioactives, which are potentially efficacious in preventing and reducing some highly prevalent CV risk factors, such as hypercholesterolemia, hypertension, vascular inflammation and vascular compliance. Some lipid- and blood pressure-lowering bioactives were studied for their impact on human vascular health, particularly as regards endothelial function and arterial stiffness. Several nutraceuticals showed additive or synergistic properties in combination, sometimes (but not always) allowing a reduction of the administered dose of extracts and determining a "multi-factorial" final effect on many cardiovascular risk factors. Thus, this review focuses on available evidence regarding the effects of berberine, plant sterols, green tea extract, soy, curcumin, cocoa, pycnogenol, lycopene, olive oil, soluble fibers, garlic, resveratrol, beetroot, mineral salts and vitamins on the lipid profile, blood pressure, inflammatory and endothelial markers, and vascular compliance. Future clinical research studies will have to focus more on middle term modification of the instrumental markers of vascular aging than on short-term effects on indirect laboratory risk markers.

Cuba: Exploring the History of Admixture and the Genetic Basis of Pigmentation Using Autosomal and Uniparental Markers

PubMed Central

Fuentes-Smith, Evelyn; Salas, Antonio; Buttenschøn, Henriette N.; Demontis, Ditte; Torres-Español, María; Marín-Padrón, Lilia C.; Gómez-Cabezas, Enrique J.; Álvarez-Iglesias, Vanesa; Mosquera-Miguel, Ana; Martínez-Fuentes, Antonio; Carracedo, Ángel; Børglum, Anders D.; Mors, Ole

2014-01-01

We carried out an admixture analysis of a sample comprising 1,019 individuals from all the provinces of Cuba. We used a panel of 128 autosomal Ancestry Informative Markers (AIMs) to estimate the admixture proportions. We also characterized a number of haplogroup diagnostic markers in the mtDNA and Y-chromosome in order to evaluate admixture using uniparental markers. Finally, we analyzed the association of 16 single nucleotide polymorphisms (SNPs) with quantitative estimates of skin pigmentation. In the total sample, the average European, African and Native American contributions as estimated from autosomal AIMs were 72%, 20% and 8%, respectively. The Eastern provinces of Cuba showed relatively higher African and Native American contributions than the Western provinces. In particular, the highest proportion of African ancestry was observed in the provinces of Guantánamo (40%) and Santiago de Cuba (39%), and the highest proportion of Native American ancestry in Granma (15%), Holguín (12%) and Las Tunas (12%). We found evidence of substantial population stratification in the current Cuban population, emphasizing the need to control for the effects of population stratification in association studies including individuals from Cuba. The results of the analyses of uniparental markers were concordant with those observed in the autosomes. These geographic patterns in admixture proportions are fully consistent with historical and archaeological information. Additionally, we identified a sex-biased pattern in the process of gene flow, with a substantially higher European contribution from the paternal side, and higher Native American and African contributions from the maternal side. This sex-biased contribution was particularly evident for Native American ancestry. Finally, we observed that SNPs located in the genes SLC24A5 and SLC45A2 are strongly associated with melanin levels in the sample. PMID:25058410

Cuba: exploring the history of admixture and the genetic basis of pigmentation using autosomal and uniparental markers.

PubMed

Marcheco-Teruel, Beatriz; Parra, Esteban J; Fuentes-Smith, Evelyn; Salas, Antonio; Buttenschøn, Henriette N; Demontis, Ditte; Torres-Español, María; Marín-Padrón, Lilia C; Gómez-Cabezas, Enrique J; Alvarez-Iglesias, Vanesa; Mosquera-Miguel, Ana; Martínez-Fuentes, Antonio; Carracedo, Angel; Børglum, Anders D; Mors, Ole

2014-07-01

We carried out an admixture analysis of a sample comprising 1,019 individuals from all the provinces of Cuba. We used a panel of 128 autosomal Ancestry Informative Markers (AIMs) to estimate the admixture proportions. We also characterized a number of haplogroup diagnostic markers in the mtDNA and Y-chromosome in order to evaluate admixture using uniparental markers. Finally, we analyzed the association of 16 single nucleotide polymorphisms (SNPs) with quantitative estimates of skin pigmentation. In the total sample, the average European, African and Native American contributions as estimated from autosomal AIMs were 72%, 20% and 8%, respectively. The Eastern provinces of Cuba showed relatively higher African and Native American contributions than the Western provinces. In particular, the highest proportion of African ancestry was observed in the provinces of Guantánamo (40%) and Santiago de Cuba (39%), and the highest proportion of Native American ancestry in Granma (15%), Holguín (12%) and Las Tunas (12%). We found evidence of substantial population stratification in the current Cuban population, emphasizing the need to control for the effects of population stratification in association studies including individuals from Cuba. The results of the analyses of uniparental markers were concordant with those observed in the autosomes. These geographic patterns in admixture proportions are fully consistent with historical and archaeological information. Additionally, we identified a sex-biased pattern in the process of gene flow, with a substantially higher European contribution from the paternal side, and higher Native American and African contributions from the maternal side. This sex-biased contribution was particularly evident for Native American ancestry. Finally, we observed that SNPs located in the genes SLC24A5 and SLC45A2 are strongly associated with melanin levels in the sample.

Adaptive genetic markers discriminate migratory runs of Chinook salmon (Oncorhynchus tshawytscha) amid continued gene flow

PubMed Central

O'Malley, Kathleen G; Jacobson, Dave P; Kurth, Ryon; Dill, Allen J; Banks, Michael A

2013-01-01

Neutral genetic markers are routinely used to define distinct units within species that warrant discrete management. Human-induced changes to gene flow however may reduce the power of such an approach. We tested the efficiency of adaptive versus neutral genetic markers in differentiating temporally divergent migratory runs of Chinook salmon (Oncorhynchus tshawytscha) amid high gene flow owing to artificial propagation and habitat alteration. We compared seven putative migration timing genes to ten microsatellite loci in delineating three migratory groups of Chinook in the Feather River, CA: offspring of fall-run hatchery broodstock that returned as adults to freshwater in fall (fall run), spring-run offspring that returned in spring (spring run), and fall-run offspring that returned in spring (FRS). We found evidence for significant differentiation between the fall and federally listed threatened spring groups based on divergence at three circadian clock genes (OtsClock1b, OmyFbxw11, and Omy1009UW), but not neutral markers. We thus demonstrate the importance of genetic marker choice in resolving complex life history types. These findings directly impact conservation management strategies and add to previous evidence from Pacific and Atlantic salmon indicating that circadian clock genes influence migration timing. PMID:24478800

High genetic load in the Pacific oyster Crassostrea gigas.

PubMed Central

Launey, S; Hedgecock, D

2001-01-01

The causes of inbreeding depression and the converse phenomenon of heterosis or hybrid vigor remain poorly understood despite their scientific and agricultural importance. In bivalve molluscs, related phenomena, marker-associated heterosis and distortion of marker segregation ratios, have been widely reported over the past 25 years. A large load of deleterious recessive mutations could explain both phenomena, according to the dominance hypothesis of heterosis. Using inbred lines derived from a natural population of Pacific oysters and classical crossbreeding experiments, we compare the segregation ratios of microsatellite DNA markers at 6 hr and 2-3 months postfertilization in F(2) or F(3) hybrid families. We find evidence for strong and widespread selection against identical-by-descent marker homozygotes. The marker segregation data, when fit to models of selection against linked deleterious recessive mutations and extrapolated to the whole genome, suggest that the wild founders of inbred lines carried a minimum of 8-14 highly deleterious recessive mutations. This evidence for a high genetic load strongly supports the dominance theory of heterosis and inbreeding depression and establishes the oyster as an animal model for understanding the genetic and physiological causes of these economically important phenomena. PMID:11560902

Simulating transfer and persistence of a chemical marker powder for Lycopodium clavatum spores.

PubMed

Howarth, Jennifer; Coulson, Sally; Newton, Angus

2009-11-20

In this research a chemical marker powder, based on Lycopodium clavatum spores, was studied to determine its transfer and persistence on a T-shirt. Such chemical marker powders are used to provide evidence that a person has handled a covertly marked object, such as a drug package. The powder was found to transfer readily between a marked item and the person handling it. The powder was found to persist on a T-shirt for up to 13h; however, there was only a very small amount of powder remaining at this time. The rate of loss of the L. clavatum spores was found to follow a decay curve. The largest decrease in spores from the T-shirt was seen in the first 2h after the marked item had been handled.

Narrowing the position of the Treacher Collins syndrome locus to a small interval between three new microsatellite markers at 5q32-33. 1

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

Dixon, M.J.; Dixon, J.; Houseal, T.

Treacher Collins syndrome (TCOF1) is an autosomal dominant disorder of craniofacial development, the features of which include conductive hearing loss and cleft palate. The TCOF1 locus has been localized to chromosome 5q32-33.2. In the present study the authors have used the combined techniques of genetic linkage analysis and fluorescence in situ hybridization (FISH) to more accurately define the TCOF1 critical region. Cosmids IG90 and SPARC, which map to distal 5q, encompass two and one hypervariable microsatellite markers, respectively. The heterozygosity values of these three markers range from .72 to .81. Twenty-two unrelated TCOF1 families have been analyzed for linkage tomore » these markers. There is strong evidence demonstrating linkage to all three markers, the strongest support for positive linkage being provided by haplotyping those markers at the locus encompassed by the cosmid IG90 (Z[sub max]= 19.65; 0 = .010). FISH to metaphase chromosomes and interphase nuclei established that IG90 lies centromeric to SPARC. This information combined with the data generated by genetic linkage analysis demonstrated that the TCOF1 locus is closely flanked proximally by IG90 and distally by SPARC. 30 refs., 2 figs., 4 tabs.« less

Polymorphic microsatellite markers for the rare and endangered cactus Uebelmannia pectinifera (Cactaceae) and its congeneric species.

PubMed

Moraes, E M; Cidade, F W; Silva, G A R; Machado, M C

2014-12-04

The cactus genus Uebelmannia includes 3 narrow endemic species associated with rocky savanna habitats in eastern South America. Because of their rarity and illegal over-collection, all of these species are endangered. Taxonomic uncertainties resulting from dramatic local variation in morphology within Uebelmannia species preclude effective conservation efforts, such as the reintroduction or translocation of plants, to restore declining populations. In this study, we developed and characterized 18 perfect, dinucleotide simple-sequence repeat markers for U. pectinifera, the most widely distributed species in the genus, and tested the cross-amplification of these markers in the remaining congeneric species and subspecies. All markers were polymorphic in a sample from 2 U. pectinifera populations. The effective number of alleles ranged from 1.6 to 8.7, with an average per population of 3.3 (SE ± 0.30) and 4.5 (SE ± 0.50). Expected heterozygosity ranged from 0.375 to 0.847 and 8-10 loci showed departures from Hardy- Weinberg equilibrium in the analyzed populations. Based on the observed polymorphism level of each marker, as well as the analysis of null allele presence and evidence of amplification of duplicate loci, a subset of 12 loci can be used as reliable markers to investigate the genetic structure, diversity, and species limits of the Uebelmannia genus.

Phylogeny and systematics of the brake fern genus Pteris (Pteridaceae) based on molecular (plastid and nuclear) and morphological evidence.

PubMed

Zhang, Liang; Zhang, Li-Bing

2018-01-01

The brake fern genus Pteris belongs to Pteridaceae subfamily Pteridoideae. It is one of the largest fern genera and has been estimated to contain 200-250 species distributed on all continents except Antarctica. Previous studies were either based on plastid data only or based on both plastid and nuclear data but the sampling was small. In addition, an infrageneric classification of Pteris based on morphological and molecular evidence has not been available yet. In the present study, based on molecular data of eight plastid markers and one nuclear marker (gapCp) of 256 accessions representing ca. 178 species of Pteris, we reconstruct a global phylogeny of Pteris. The 15 major clades identified earlier are recovered here and we further identified a new major clade. Our nuclear phylogeny recovered 11 of these 16 major clades, seven of which are strongly supported. The inclusion of Schizostege in Pteris is confirmed for the first time. Based on the newly reconstructed phylogeny and evidence from morphology, distribution and/or ecology, we classify Pteris into three subgenera: P. subg. Pteris, P. subg. Campteria, and P. subg. Platyzoma. The former two are further divided into three and 12 sections, respectively. Copyright © 2017 Elsevier Inc. All rights reserved.

Pediatric Bipolar Disorder: Evidence for Prodromal States and Early Markers

ERIC Educational Resources Information Center

Luby, Joan L.; Navsaria, Neha

2010-01-01

Background: Childhood bipolar disorder remains a controversial but increasingly diagnosed disorder that is associated with significant impairment, chronic course and treatment resistance. Therefore, the search for prodromes or early markers of risk for later childhood bipolar disorder may be of great importance for prevention and/or early…

Toward Diagnostic and Phenotype Markers for Genetically Transmitted Speech Delay

ERIC Educational Resources Information Center

Shriberg, Lawrence D.; Lewis, Barbara A.; Tomblin, J. Bruce; McSweeny, Jane L.; Karlsson, Heather B.; Scheer, Alison R.

2005-01-01

Converging evidence supports the hypothesis that the most common subtype of childhood speech sound disorder (SSD) of currently unknown origin is genetically transmitted. We report the first findings toward a set of diagnostic markers to differentiate this proposed etiological subtype (provisionally termed "speech delay-genetic") from other…

Structural changes in endometrial basal glands during menstruation.

PubMed

Garry, R; Hart, R; Karthigasu, K A; Burke, C

2010-09-01

To prospectively observe the changes occurring in endometrial glandular morphology during menstrual shedding and regeneration. Prospective observational study. The academic gynaecological endoscopy unit of a university teaching hospital. Population Thirteen patients investigated for a variety of benign, non-infective gynaecological disorders during the active bleeding phase of the menstrual cycle. The morphological appearances of concurrent histological and scanning electron microscopic images of endometrium taken at different stages of the active bleeding phase of menstruation were studied and correlated with the simultaneous immunohistochemical expression of the Ki-67 proliferation marker and the CD68 marker of macrophage activity. Change in morphology of endometrial glands at various stages of menstruation. Endometrial glands within the basalis show evidence of apoptosis and associated macrophage activity immediately before and during menstruation. There is subsequent destruction and removal of old secretory glandular epithelial elements, and rapid replacement with new narrow glands lined with small epithelial cells. There is no evidence of mitotic cell division or expression of Ki-67 in the glandular cells during this replacement process, but there is evidence of marked macrophage activity prior to glandular cell loss. Early endometrial epithelial repair after menstruation is not a consequence of mitotic cell division. It occurs without evidence of Ki-67 expression. There is structural evidence of programmed cell death and intense macrophage activity associated with glandular remodelling. Dead epithelial cells are shed from the glands and accumulate within the endometrial cavity to be replaced by new small epithelial cells that appear to arise by differentiation of the surrounding stromal cells. We propose that these stromal cells are endometrial progenitor/stem cells.

Molecular Ultrasound Imaging for the Detection of Neural Inflammation

NASA Astrophysics Data System (ADS)

Volz, Kevin R.

Molecular imaging is a form of nanotechnology that enables the noninvasive examination of biological processes in vivo. Radiopharmaceutical agents are used to selectively target biochemical markers, which permits their detection and evaluation. Early visualization of molecular variations indicative of pathophysiological processes can aid in patient diagnoses and management decisions. Molecular imaging is performed by introducing molecular probes into the body. Molecular probes are often contrast agents that have been nanoengineered to selectively target and tether to molecules, enabling their radiologic identification. Ultrasound contrast agents have been demonstrated as an effective method of detecting perfusion at the tissue level. Through a nanoengineering process, ultrasound contrast agents can be targeted to specific molecules, thereby extending ultrasound's capabilities from the tissue to molecular level. Molecular ultrasound, or targeted contrast enhanced ultrasound (TCEUS), has recently emerged as a popular molecular imaging technique due to its ability to provide real-time anatomical and functional information in the absence of ionizing radiation. However, molecular ultrasound represents a novel form of molecular imaging, and consequently remains largely preclinical. A review of the TCEUS literature revealed multiple preclinical studies demonstrating its success in detecting inflammation in a variety of tissues. Although, a gap was identified in the existing evidence, as TCEUS effectiveness for detection of neural inflammation in the spinal cord was unable to be uncovered. This gap in knowledge, coupled with the profound impacts that this TCEUS application could have clinically, provided rationale for its exploration, and use as contributory evidence for the molecular ultrasound body of literature. An animal model that underwent a contusive spinal cord injury was used to establish preclinical evidence of TCEUS to detect neural inflammation. Imaging was performed while targeting three early inflammatory markers (P-selectin, VCAM-1, ICAM-1). Imaging protocols and outcome measures of previous TCEUS investigations of inflammation were replicated to aid in comparisons of outcomes. Signal intensity data was used to generate time intensity curves for qualitative and quantitative analysis of contrast agent temporal behavior. A proof of principle study established preclinical evidence to support the ability of TCEUS to detect acute neural inflammation. Substantial increases in signal intensities were observed while targeting inflammatory markers compared to controls. Further investigations consisted of examining molecular ultrasound sensitivity, and were accomplished by examining targeted contrast agent dosing parameters, and the ability of TCEUS to longitudinally evaluate neural inflammation. Qualitative analysis of TCEUS imaging performed with both administered doses revealed marked increases in signal intensities during acute inflammation, where inflammatory marker expression was presumably at its highest. This was in comparison to measures obtained in the absence of, and during, chronic inflammation. This research contributes much needed empirical evidence to the molecular ultrasound body of literature, and represents the first steps towards advancing this TCEUS application to clinical practice. Future studies are necessary to further these findings and effectively build upon this evidence. Increasing evidence of TCEUS use for the detection of neural inflammation will aid in its eventual clinical translation, where it will likely have a positive impact on patient care.

Shared biomarkers between female diastolic heart failure and pre‐eclampsia: a systematic review and meta‐analysis

PubMed Central

Bokslag, Anouk; Maas, Angela H.E.M.; Franx, Arie; Paulus, Walter J.; de Groot, Christianne J.M.

2017-01-01

Abstract Evidence accumulates for associations between hypertensive pregnancy disorders and increased cardiovascular risk later. The main goal of this study was to explore shared biomarkers representing common pathogenic pathways between heart failure with preserved ejection fraction (HFpEF) and pre‐eclampsia where these biomarkers might be potentially eligible for cardiovascular risk stratification in women after hypertensive pregnancy disorders. We sought for blood markers in women with diastolic dysfunction in a first literature search, and through a second search, we investigated whether these same biochemical markers were present in pre‐eclampsia.This systematic review and meta‐analysis presents two subsequent systematic searches in PubMed and EMBASE. Search I yielded 3014 studies on biomarkers discriminating women with HFpEF from female controls, of which 13 studies on 11 biochemical markers were included. Cases had HFpEF, and controls had no heart failure. The second search was for studies discriminating women with pre‐eclampsia from women with non‐hypertensive pregnancies with at least one of the biomarkers found in Search I. Search II yielded 1869 studies, of which 51 studies on seven biomarkers were included in meta‐analyses and 79 studies on 12 biomarkers in systematic review.Eleven biological markers differentiated women with diastolic dysfunction from controls, of which the following 10 markers differentiated women with pre‐eclampsia from controls as well: C‐reactive protein, HDL, insulin, fatty acid‐binding protein 4, brain natriuretic peptide, N terminal pro brain natriuretic peptide, adrenomedullin, mid‐region pro adrenomedullin, cardiac troponin I, and cancer antigen 125.Our study supports the hypothesis that HFpEF in women shares a common pathogenic background with pre‐eclampsia. The biomarkers representing inflammatory state, disturbances in myocardial function/structure, and unfavourable lipid metabolism may possibly be eligible for future prognostic tools. PMID:28451444

Selective insulin resistance in hepatocyte senescence

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

Aravinthan, Aloysious; Challis, Benjamin; Shannon, Nicholas

Insulin resistance has been described in association with chronic liver disease for decades. Hepatocyte senescence has been demonstrated in chronic liver disease and as many as 80% of hepatocytes show a senescent phenotype in advanced liver disease. The aim of this study was to understand the role of hepatocyte senescence in the development of insulin resistance. Senescence was induced in HepG2 cells via oxidative stress. The insulin metabolic pathway was studied in control and senescent cells following insulin stimulation. GLUT2 and GLUT4 expressions were studied in HepG2 cells and human liver tissue. Further, GLUT2 and GLUT4 expressions were studied inmore » three independent chronic liver disease cohorts. Signalling impairment distal to Akt in phosphorylation of AS160 and FoxO1 was evident in senescent HepG2 cells. Persistent nuclear localisation of FoxO1 was demonstrated in senescent cells despite insulin stimulation. Increased GLUT4 and decreased GLUT2 expressions were evident in senescent cells, human cirrhotic liver tissue and publically available liver disease datasets. Changes in GLUT expressions were associated with a poor clinical prognosis. In conclusion, selective insulin resistance is evident in senescent HepG2 cells and changes in GLUT expressions can be used as surrogate markers of hepatocyte senescence. - Highlights: • Senescent hepatocytes demonstrate selective insulin resistance. • GLUT changes act as markers of hepatocyte senescence and have prognostic value. • Study offers insight into long noticed intimacy of cirrhosis and insulin resistance.« less

A Review on the Role of Inflammation in Attention-Deficit/Hyperactivity Disorder.

PubMed

Leffa, Douglas Teixeira; Torres, Iraci L S; Rohde, Luis Augusto

2018-06-06

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental condition that impairs quality of life in social, academic, and occupational contexts for both children and adults. Although a strong neurobiological basis has been demonstrated, the pathophysiology of ADHD is still poorly understood. Among the proposed mechanisms are glial activation, neuronal damage and degeneration, increased oxidative stress, reduced neurotrophic support, altered neurotransmitter metabolism, and blood-brain barrier disruption. In this way, a potential role of inflammation has been increasingly researched. However, evidence for the involvement of inflammation in ADHD is still scarce and comes mainly from (1) observational studies showing a strong comorbidity of ADHD with inflammatory and autoimmune disorders; (2) studies evaluating serum inflammatory markers; and (3) genetic studies. A co-occurrence of ADHD with inflammatory disorders has been demonstrated in a large number of subjects, suggesting a range of underlying mechanisms such as an altered immune response, common genetics, and environmental links. The evaluation of serum inflammatory markers has provided mixed results, likely due to the small sample sizes and high heterogeneity between biomarkers. However, there is evidence that increased inflammation during the early development may be a risk factor for ADHD symptoms. Although genetic studies have demonstrated a potential role for inflammation in this disorder, there is no clear evidence. To sum up, inflammation may be an important mechanism in ADHD pathophysiology, but more studies are still needed for a more precise conclusion. © 2018 S. Karger AG, Basel.

The Pelagos Sanctuary for Mediterranean marine mammals: Marine Protected Area (MPA) or marine polluted area? The case study of the striped dolphin (Stenella coeruleoalba).

PubMed

Fossi, Maria Cristina; Panti, Cristina; Marsili, Letizia; Maltese, Silvia; Spinsanti, Giacomo; Casini, Silvia; Caliani, Ilaria; Gaspari, Stefania; Muñoz-Arnanz, Juan; Jimenez, Begoña; Finoia, Maria Grazia

2013-05-15

The concurrence of man-made pressures on cetaceans in the Mediterranean Sea is potentially affecting population stability and marine biodiversity. This needs to be proven for the only pelagic marine protected area in the Mediterranean Sea: the Pelagos Sanctuary for Mediterranean Marine Mammals. Here we applied a multidisciplinary tool, using diagnostic markers elaborated in a statistical model to rank toxicological stress in Mediterranean cetaceans. As a case study we analyzed persistent, bioaccumulative and toxic chemicals combined with a wide range of diagnostic markers of exposure to anthropogenic contaminants and genetic variation as marker of genetic erosion in striped dolphin (Stenella coeruleoalba) skin biopsies. Finally, a statistical model was applied to obtain a complete toxicological profile of the striped dolphin in the Pelagos Sanctuary and other Mediterranean areas (Ionian Sea and Strait of Gibraltar). Here we provide the first complete evidence of the toxicological stress in cetaceans living in Pelagos Sanctuary. Copyright © 2013 Elsevier Ltd. All rights reserved.

Application of Faecalibacterium 16S rDNA genetic marker for accurate identification of duck faeces.

PubMed

Sun, Da; Duan, Chuanren; Shang, Yaning; Ma, Yunxia; Tan, Lili; Zhai, Jun; Gao, Xu; Guo, Jingsong; Wang, Guixue

2016-04-01

The aim of this study was to judge the legal duty of pollution liabilities by assessing a duck faeces-specific marker, which can exclude distractions of residual bacteria from earlier contamination accidents. With the gene sequencing technology and bioinformatics method, we completed the comparative analysis of Faecalibacterium sequences, which were associated with ducks and other animal species, and found the sequences unique to duck faeces. Polymerase chain reaction (PCR) and agarose gel electrophoresis techniques were used to verify the reliability of both human and duck faeces-specific primers. The duck faeces-specific primers generated an amplicon of 141 bp from 43.3 % of duck faecal samples, 0 % of control samples and 100 % of sewage wastewater samples that contained duck faeces. We present here the initial evidence of Faecalibacterium-based applicability as human faeces-specificity in China. Meanwhile, this study represents the initial report of a Faecalibacterium marker for duck faeces and suggests an independent or supplementary environmental biotechnology of microbial source tracking (MST).

Inheritance pattern of microsatellite loci and their use for kinship analysis in the Japanese scallop Patinopecten yessoensis

NASA Astrophysics Data System (ADS)

Xu, Kefeng; Li, Qi

2009-06-01

The inheritance mode of seven microsatellite markers was investigated in Patinopecten yessoensis larvae from four controlled crosses, and the feasibility of using these markers for kinship estimation was also examined. All the seven microsatellite loci were compatible with Mendelian inheritance. Neither sex-linked barriers to transmission nor major barriers to fertilization between gametes from the parents were evident. Two of the seven loci showed the presence of null alleles in two families, suggesting the need to conduct comprehensive species-specific inheritance studies for microsatellite loci used in population genetic studies. However, even if the null allele heterozygotes were considered as homozygotes in the calculation of genetic distance, offspring from four families were all unambiguously discriminated in the neighbor-joining dendrogram. This result indicates that the microsatellite markers used may be capable of discriminating between related and unrelated scallop larvae in the absence of pedigree information, and of investigating the effective number of parents contributing to the hatchery population of the Japanese scallop.

At the Crossroads of Cancer Stem Cells, Radiation Biology, and Radiation Oncology.

PubMed

Gerweck, Leo E; Wakimoto, Hiroaki

2016-03-01

Reports that a small subset of tumor cells initiate and sustain tumor growth, are resistant to radiation and drugs, and bear specific markers have led to an explosion of cancer stem cell research. These reports imply that the evaluation of therapeutic response by changes in tumor volume is misleading, as volume changes reflect the response of the sensitive rather than the resistant tumorigenic cell population. The reports further suggest that the marker-based selection of the tumor cell population will facilitate the development of radiation treatment schedules, sensitizers, and drugs that specifically target the resistant tumorigenic cells that give rise to treatment failure. This review presents evidence that contests the observations that cancer stem cell markers reliably identify the subset of tumor cells that sustain tumor growth and that the marker-identified population is radioresistant relative to the marker-negative cells. Experimental studies show that cells and tumors that survive large radiation doses are not more radioresistant than unirradiated cells and tumors, and also show that the intrinsic radiosensitivity of unsorted colony-forming tumor cells, in combination with the fraction of unsorted tumor cells that are tumor initiating, predicts tumor radiocurability. ©2016 American Association for Cancer Research.

Inference of genetic diversity in popcorn S3 progenies.

PubMed

Pena, G F; do Amaral, A T; Ribeiro, R M; Ramos, H C C; Boechat, M S B; Santos, J S; Mafra, G S; Kamphorst, S H; de Lima, V J; Vivas, M; de Souza Filho, G A

2016-05-09

Molecular markers are a useful tool for identification of complementary heterotic groups in breeding programs aimed at the production of superior hybrids, particularly for crops such as popcorn in which heterotic groups are not well-defined. The objective of the present study was to analyze the genetic diversity of 47 genotypes of tropical popcorn to identify possible heterotic groups for the development of superior hybrids. Four genotypes of high genetic value were studied: hybrid IAC 125, strain P2, and varieties UENF 14 and BRS Angela. In addition, 43 endogamous S3 progenies obtained from variety UENF 14 were used. Twenty-five polymorphic SSR-EST markers were analyzed. A genetic distance matrix was obtained and the following molecular diversity parameters were estimated: number of alleles, number of effective alleles, polymorphism information content (PIC), observed and expected heterozygosities, Shannon diversity index, and coefficient of inbreeding. We found a moderate PIC and high diversity index, indicating that the studied population presents both good discriminatory ability and high informativeness for the utilized markers. The dendrogram built based on the dissimilarity matrix indicated six distinct groups. Our findings demonstrate the genetic diversity among the evaluated genotypes and provide evidence for heterotic groups in popcorn. Furthermore, the functional genetic diversity indicates that there are informative genetic markers for popcorn.

Nonsyndromic cleft lip and palate: Evidence of linkage to a microsatellite marker on 6p23

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

Carinci, F.; Pezzetti, F.; Scapoli, L.

1995-01-01

Nonsydromic cleft lip with or without secondary clefting of the palate (CL+/{minus}P) is one of the most common birth defects. A previous linkage study concerning CL+/{minus}P and cleft palate (CP) families indicated chromosome 6p, near F13A locus, as a possible region for the presence of a clefting gene. More recently, another linkage study performed on a sample of 12 families with nonsyndromic CL+/{minus}P seemed to exclude this association. To test the hypothesis on the possible presence of a major gene on chromosome 6p, we carried out a study on a large sample (21) of CL+/{minus}P families from northeastern Italy. Inmore » conclusion, our investigation can be summarized as follows: (i) CL+/{minus}P disease appears to be heterogeneous; (ii) {approximately}66% of the pedigrees showed an autosomal dominant inheritance with incomplete penetrance; and (iii) CL+/{minus}P locus maps on 6p23 very close to or at the microsatellite marker D6S89. To verify whether the D6S89 is the closest marker to the CL+/{minus}P locus, additional examinations with new markers are underway. 19 refs., 1 fig., 1 tab.« less

Physiological Markers of Motor Inhibition during Human Behavior.

PubMed

Duque, Julie; Greenhouse, Ian; Labruna, Ludovica; Ivry, Richard B

2017-04-01

Transcranial magnetic stimulation (TMS) studies in humans have shown that many behaviors engage processes that suppress excitability within the corticospinal tract. Inhibition of the motor output pathway has been extensively studied in the context of action stopping, where a planned movement needs to be abruptly aborted. Recent TMS work has also revealed markers of motor inhibition during the preparation of movement. Here, we review the evidence for motor inhibition during action stopping and action preparation, focusing on studies that have used TMS to monitor changes in the excitability of the corticospinal pathway. We discuss how these physiological results have motivated theoretical models of how the brain selects actions, regulates movement initiation and execution, and switches from one state to another. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dissociable Genetic Contributions to Error Processing: A Multimodal Neuroimaging Study

PubMed Central

Agam, Yigal; Vangel, Mark; Roffman, Joshua L.; Gallagher, Patience J.; Chaponis, Jonathan; Haddad, Stephen; Goff, Donald C.; Greenberg, Jennifer L.; Wilhelm, Sabine; Smoller, Jordan W.; Manoach, Dara S.

2014-01-01

Background Neuroimaging studies reliably identify two markers of error commission: the error-related negativity (ERN), an event-related potential, and functional MRI activation of the dorsal anterior cingulate cortex (dACC). While theorized to reflect the same neural process, recent evidence suggests that the ERN arises from the posterior cingulate cortex not the dACC. Here, we tested the hypothesis that these two error markers also have different genetic mediation. Methods We measured both error markers in a sample of 92 comprised of healthy individuals and those with diagnoses of schizophrenia, obsessive-compulsive disorder or autism spectrum disorder. Participants performed the same task during functional MRI and simultaneously acquired magnetoencephalography and electroencephalography. We examined the mediation of the error markers by two single nucleotide polymorphisms: dopamine D4 receptor (DRD4) C-521T (rs1800955), which has been associated with the ERN and methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133), which has been associated with error-related dACC activation. We then compared the effects of each polymorphism on the two error markers modeled as a bivariate response. Results We replicated our previous report of a posterior cingulate source of the ERN in healthy participants in the schizophrenia and obsessive-compulsive disorder groups. The effect of genotype on error markers did not differ significantly by diagnostic group. DRD4 C-521T allele load had a significant linear effect on ERN amplitude, but not on dACC activation, and this difference was significant. MTHFR C677T allele load had a significant linear effect on dACC activation but not ERN amplitude, but the difference in effects on the two error markers was not significant. Conclusions DRD4 C-521T, but not MTHFR C677T, had a significant differential effect on two canonical error markers. Together with the anatomical dissociation between the ERN and error-related dACC activation, these findings suggest that these error markers have different neural and genetic mediation. PMID:25010186

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

Banding studies on chromosomes in diffuse histiocytic lymphomas: correlation of 14q+ marker chromosome with cytology

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

Fukuhara, S.; Rowley, J.D.; Variakojis, D.

1978-11-01

Chromosomes were studied in cells from tissues primarily involved by diffuse histiocytic lymphoma in nine patients. Two of the patients had stage II disease; their tumors were fibrotic and had no mitotic cells. One patient was in stage III, and the remaining six patients had stage IV disease. The modal chromosome number of abnormal cells from these last seven patients was hypodiploid in two, hyperdiploid in four, and near-triploid in one. Complete banding studies of six cases and partial analysis of the seventh indicate that (1) every patient had a distinct cell line with common markers, with a few cellsmore » showing minor variants; (2) although certain chromosomes (Nos. 1, 2, 3, 9, 12, and 14) were structurally affected more often than others, no markers with the same banding pattern were noted among them; and (3) the cytologic type of lymphoma could be correlated with the karyotype in all seven patients. When the Lukes and Collins classification was used, three patients whose tumors were composed predominantly of large noncleaved cells showed a 14q translocation leading to the formation of a 14q+ marker chromosome. This marker was not observed in four patients whose tumors had a majority of large cleaved cells. These preliminary results, if confirmed in a larger series of patients, will provide additional evidence that there are consistent chromosome changes associated with specific subtypes of lymphoproliferative disorders analogous to the Ph/sup 1/ chromosome in chronic myelogenous leukemia.« less

Changes in biochemical markers after lower limb fractures.

PubMed

Stoffel, Karl; Engler, Hanna; Kuster, Markus; Riesen, Walter

2007-01-01

The bone remodeling sequence after bone fracture changes the concentrations of biochemical bone markers, but the relationships of fracture size and of healing time to changes in biomarkers are unclear. The present pilot study was undertaken to determine the changes found in serum bone markers after plate osteosynthesis of closed distal tibial and malleolar fractures during a study period of 24 weeks. We measured tatrate-resistant acid phosphatase (TRACP 5b), collagen type I C-terminal telopeptide (ICTP), bone-specific alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen type I C-terminal propeptide (PICP), procollagen type III N-terminal propeptide (PIIINP), and human cartilage glycoprotein 39 (YKL-40) in 20 patients with lower limb fractures (10 malleolar, 10 tibia). A physical examination and radiographs were completed to assess evidence of union. All malleolar fractures healed within 6 weeks, whereas 2 tibial fractures did not show complete bone healing after 24 weeks. Changes were comparable but more pronounced in the tibia group, and marker concentrations remained increased at the end of study (bone ALP, 86 vs 74 U/L; OC, 14.9 vs 7.7 microg/L; ICTP: 5.6 vs 3.3 microg/L at day 84 after osteosynthesis, P <0.05 in tibia; 80 vs 70 U/L, 8 vs 5.2 microg/L, and 3.5 vs 3.2 microg/L, respectively, in the malleolar fracture group). In normal bone healing, changes in bone turnover markers were primarily dependent on the fracture size. Delayed tibia fracture healing may involve a disturbance in bone remodeling.

Analytical Rubrics in Higher Education: A Repository of Empirical Data

ERIC Educational Resources Information Center

Hack, Catherine

2015-01-01

The use of rubrics for grading and feedback in higher education has increased in response to requirements for consistency and transparency across a diverse range of assessment tasks. There is a growing evidence base demonstrating the reliability of rubrics across different markers and instances. The number of studies describing the impact of…

EVIDENCE FOR LANDSCAPE LEVEL, POLLEN-MEDIATED GENE FLOW FROM CREEPING BENTGRASS WITH CP4 EPSPS AS A MARKER

EPA Science Inventory

In a landscape level study, gene flow via pollen was tracked from multiple source fields of genetically modified (GM) herbicide resistant creeping bentgrass (Agrostis stolonifera L.) to 75 of 138 sentinel plants of A. stolonifera and to 29 of 69 resident populations of Agrostis s...

Causes and Consequences of Early Life Health. NBER Working Paper No. 15637

ERIC Educational Resources Information Center

Case, Anne; Paxson, Christina

2010-01-01

We examine the consequences of childhood health for economic and health outcomes in adulthood, using height as a marker of health in childhood. After reviewing previous evidence, we present a conceptual framework that highlights data limitations and methodological problems associated with the study of this topic. We present estimates of the…

The Genetic Architecture of Complex Traits in Teosinte (Zea mays ssp. parviglumis): New Evidence from Association Mapping

USDA-ARS?s Scientific Manuscript database

Our previous association analyses showed that variation at major regulatory genes contributes to standing variation for complex traits in Balsas teosinte, the progenitor of maize. This study expands our previous association mapping effort in teosinte by testing 123 markers in 52 candidate genes for ...

Cryptosporidium hominis Infection of the Human Respiratory Tract

PubMed Central

Buck, Gregory A.; Manque, Patricio A.; Ozaki, Luiz Shozo

2007-01-01

Cryptosporidium oocysts, observed in a natural sputum sample of a patient with HIV, were further studied by using DNA markers to determine the species of the parasite. C. hominis was identified as the species infecting the patient’s respiratory tract, a finding that strengthens evidence regarding this pathogen’s role in human disease. PMID:17552101

Integration of hybridization-based markers (overgos) into physical maps for comparative and evolutionary explorations in the genus Oryza and in Sorghum

PubMed Central

Hass-Jacobus, Barbara L; Futrell-Griggs, Montona; Abernathy, Brian; Westerman, Rick; Goicoechea, Jose-Luis; Stein, Joshua; Klein, Patricia; Hurwitz, Bonnie; Zhou, Bin; Rakhshan, Fariborz; Sanyal, Abhijit; Gill, Navdeep; Lin, Jer-Young; Walling, Jason G; Luo, Mei Zhong; Ammiraju, Jetty Siva S; Kudrna, Dave; Kim, Hye Ran; Ware, Doreen; Wing, Rod A; Miguel, Phillip San; Jackson, Scott A

2006-01-01

Background With the completion of the genome sequence for rice (Oryza sativa L.), the focus of rice genomics research has shifted to the comparison of the rice genome with genomes of other species for gene cloning, breeding, and evolutionary studies. The genus Oryza includes 23 species that shared a common ancestor 8–10 million years ago making this an ideal model for investigations into the processes underlying domestication, as many of the Oryza species are still undergoing domestication. This study integrates high-throughput, hybridization-based markers with BAC end sequence and fingerprint data to construct physical maps of rice chromosome 1 orthologues in two wild Oryza species. Similar studies were undertaken in Sorghum bicolor, a species which diverged from cultivated rice 40–50 million years ago. Results Overgo markers, in conjunction with fingerprint and BAC end sequence data, were used to build sequence-ready BAC contigs for two wild Oryza species. The markers drove contig merges to construct physical maps syntenic to rice chromosome 1 in the wild species and provided evidence for at least one rearrangement on chromosome 1 of the O. sativa versus Oryza officinalis comparative map. When rice overgos were aligned to available S. bicolor sequence, 29% of the overgos aligned with three or fewer mismatches; of these, 41% gave positive hybridization signals. Overgo hybridization patterns supported colinearity of loci in regions of sorghum chromosome 3 and rice chromosome 1 and suggested that a possible genomic inversion occurred in this syntenic region in one of the two genomes after the divergence of S. bicolor and O. sativa. Conclusion The results of this study emphasize the importance of identifying conserved sequences in the reference sequence when designing overgo probes in order for those probes to hybridize successfully in distantly related species. As interspecific markers, overgos can be used successfully to construct physical maps in species which diverged less than 8 million years ago, and can be used in a more limited fashion to examine colinearity among species which diverged as much as 40 million years ago. Additionally, overgos are able to provide evidence of genomic rearrangements in comparative physical mapping studies. PMID:16895597

Heart rate variability predicts alcohol craving in alcohol dependent outpatients: further evidence for HRV as a psychophysiological marker of self-regulation.

PubMed

Quintana, Daniel S; Guastella, Adam J; McGregor, Iain S; Hickie, Ian B; Kemp, Andrew H

2013-09-01

Past research has highlighted an important role of the autonomic nervous system in alcohol dependence and capacity for self-regulation. While previous studies have examined alcohol dependent inpatients, it remains unclear whether resting-state HRV, a potential psychophysiological marker of ones capacity for self-regulation, is related to craving in patients who currently consume alcohol. Thus, the aim of the present study was to determine whether HRV predicts alcohol craving in dependent individuals in the community. Resting-state HRV and alcohol craving, as indexed by the obsessive compulsive drinking scale, were assessed in 26 alcohol dependent outpatients. Results supported hypotheses indicating that HRV accounts for an additional 12.1% of the variance in craving after controlling for age, anxiety and levels of alcohol consumption. Here we show for the first time that resting-state HRV predicts craving in alcohol dependent outpatients. Results provide important new evidence for a role of the autonomic nervous system in the maintenance of dependence disorders. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Morphofunctional and signaling molecules overlap of the pineal gland and thymus: role and significance in aging.

PubMed

Paltsev, Michael A; Polyakova, Victoria O; Kvetnoy, Igor M; Anderson, George; Kvetnaia, Tatiana V; Linkova, Natalia S; Paltseva, Ekaterina M; Rubino, Rosa; De Cosmo, Salvatore; De Cata, Angelo; Mazzoccoli, Gianluigi

2016-03-15

Deficits in neuroendocrine-immune system functioning, including alterations in pineal and thymic glands, contribute to aging-associated diseases. This study looks at ageing-associated alterations in pineal and thymic gland functioning evaluating common signaling molecules present in both human and animal pinealocytes and thymocytes: endocrine cell markers (melatonin, serotonin, pCREB, AANAT, CGRP, VIP, chromogranin А); cell renovation markers (p53, AIF, Ki67), matrix metalloproteinases (MMP2, MMP9) and lymphocytes markers (CD4, CD5, CD8, CD20). Pineal melatonin is decreased, as is one of the melatonin pathway synthesis enzymes in the thymic gland. A further similarity is the increased MMPs levels evident over age in both glands. Significant differences are evident in cell renovation processes, which deteriorate more quickly in the aged thymus versus the pineal gland. Decreases in the number of pineal B-cells and thymic T-cells were also observed over aging. Collected data indicate that cellular involution of the pineal gland and thymus show many commonalities, but also significant changes in aging-associated proteins. It is proposed that such ageing-associated alterations in these two glands provide novel pharmaceutical targets for the wide array of medical conditions that are more likely to emerge over the course of ageing.

Morphofunctional and signaling molecules overlap of the pineal gland and thymus: role and significance in aging

PubMed Central

Paltsev, Michael A.; Polyakova, Victoria O.; Kvetnoy, Igor M.; Anderson, George; Kvetnaia, Tatiana V.; Linkova, Natalia S.; Paltseva, Ekaterina M.; Rubino, Rosa; De Cosmo, Salvatore; De Cata, Angelo; Mazzoccoli, Gianluigi

2016-01-01

Deficits in neuroendocrine-immune system functioning, including alterations in pineal and thymic glands, contribute to aging-associated diseases. This study looks at ageing-associated alterations in pineal and thymic gland functioning evaluating common signaling molecules present in both human and animal pinealocytes and thymocytes: endocrine cell markers (melatonin, serotonin, pCREB, AANAT, CGRP, VIP, chromogranin A); cell renovation markers (p53, AIF, Ki67), matrix metalloproteinases (MMP2, MMP9) and lymphocytes markers (CD4, CD5, CD8, CD20). Pineal melatonin is decreased, as is one of the melatonin pathway synthesis enzymes in the thymic gland. A further similarity is the increased MMPs levels evident over age in both glands. Significant differences are evident in cell renovation processes, which deteriorate more quickly in the aged thymus versus the pineal gland. Decreases in the number of pineal B-cells and thymic T-cells were also observed over aging. Collected data indicate that cellular involution of the pineal gland and thymus show many commonalities, but also significant changes in aging-associated proteins. It is proposed that such ageing-associated alterations in these two glands provide novel pharmaceutical targets for the wide array of medical conditions that are more likely to emerge over the course of ageing. PMID:26943046

Autosomal Dominant Nonsyndromic Cleft Lip and Palate: Significant Evidence of Linkage at 18q21.1

PubMed Central

Beiraghi, Soraya ; Nath, Swapan K. ; Gaines, Matthew ; Mandhyan, Desh D. ; Hutchings, David ; Ratnamala, Uppala ; McElreavey, Ken ; Bartoloni, Lucia ; Antonarakis, Gregory S. ; Antonarakis, Stylianos E. ; Radhakrishna, Uppala 

2007-01-01

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common congenital facial defects, with an incidence of 1 in 700–1,000 live births among individuals of European descent. Several linkage and association studies of NSCL/P have suggested numerous candidate genes and genomic regions. A genomewide linkage analysis of a large multigenerational family (UR410) with NSCL/P was performed using a single-nucleotide–polymorphism array. Nonparametric linkage (NPL) analysis provided significant evidence of linkage for marker rs728683 on chromosome 18q21.1 (NPL=43.33 and P=.000061; nonparametric LOD=3.97 and P=.00001). Parametric linkage analysis with a dominant mode of inheritance and reduced penetrance resulted in a maximum LOD score of 3.61 at position 47.4 Mb on chromosome 18q21.1. Haplotype analysis with informative crossovers defined a 5.7-Mb genomic region spanned by proximal marker rs1824683 (42,403,918 bp) and distal marker rs768206 (48,132,862 bp). Thus, a novel genomic region on 18q21.1 was identified that most likely harbors a high-risk variant for NSCL/P in this family; we propose to name this locus “OFC11” (orofacial cleft 11). PMID:17564975

Molecular alterations and biomarkers in colorectal cancer

PubMed Central

Grady, William M.; Pritchard, Colin C.

2013-01-01

The promise of precision medicine is now a clinical reality. Advances in our understanding of the molecular genetics of colorectal cancer genetics is leading to the development of a variety of biomarkers that are being used as early detection markers, prognostic markers, and markers for predicting treatment responses. This is no more evident than in the recent advances in testing colorectal cancers for specific molecular alterations in order to guide treatment with the monoclonal antibody therapies cetuximab and panitumumab, which target the epidermal growth factor receptor (EGFR). In this review, we update a prior review published in 2010 and describe our current understanding of the molecular pathogenesis of colorectal cancer and how these alterations relate to emerging biomarkers for early detection and risk stratification (diagnostic markers), prognosis (prognostic markers), and the prediction of treatment responses (predictive markers). PMID:24178577

Deep divergence and apparent sex-biased dispersal revealed by a Y-linked marker in rainbow trout

PubMed Central

Brunelli, Joseph P.; Steele, Craig A.; Thorgaard, Gary H.

2010-01-01

Y-chromosome and mitochondrial DNA markers can reveal phylogenetic patterns by allowing tracking of male and female lineages, respectively. We used sequence data from a recently discovered Y-linked marker and a mitochondrial marker to examine phylogeographic structure in the widespread and economically important rainbow trout (Oncorhynchus mykiss). Two distinct geographic groupings that generally correspond to coastal and inland subspecies were evident within the Y marker network while the mtDNA haplotype network showed little geographic structure. Our results suggest that male-specific behavior has prevented widespread admixture of Y haplotypes and that gene flow between the coastal and inland subspecies has largely occurred through females. This new Y marker may also aid conservation efforts by genetically identifying inland populations that have not hybridized with widely stocked coastal-derived hatchery fish. PMID:20546904

Markers of immunity and bacterial translocation in cirrhosis.

PubMed

Mortensen, Christian

2015-07-01

Bacterial translocation (BT), the migration of enteric bacteria to extraintestinal sites, is related to immune stimulation and haemodynamic changes in experimental cirrhosis. These changes may be highly relevant to patients with cirrhosis, where changes in the circulation cause serious complications. The optimal surrogate marker of BT in patients with cirrhosis, however, is a matter of controversy. In the first study, we investigated the relationship between markers of inflammation, haemodynamics and prognosis in 45 patients and 12 controls. We found high-sensitive C-reactive protein to be correlated to portal hypertension, a clinically relevant haemodynamic alteration, and appeared to be associated with increased mortality. To assess the consequences of BT on immunity, we developed an assay for the detection of bacterial DNA (bDNA), a novel marker of BT. Using the assay in the second study, in 38 patients with ascites, we found no association between bDNA and immunity, in contrast to some previous findings. In the final paper, exploring one possible translocation route, we hypothesized a difference in bDNA levels between the blood from the veins draining the gut on one hand and the liver on the other. Collecting samples during the insertion of a shunt between the two vessels in 28 patients, our finding did not suggest marked differences in bDNA, but conversely to expectations, suggested marked hepatic production of two markers of inflammation. The main results of the present thesis support some concepts of current thinking on cirrhosis pathophysiology, including the relationship of markers of inflammation to  haemodynamics, disease stage and prognosis. Our results also add to a growing body of evidence suggesting that bDNA is not a clinically relevant marker of BT.

Chromogranin A as circulating marker for diagnosis and management of neuroendocrine neoplasms: more flaws than fame.

PubMed

Marotta, Vincenzo; Zatelli, Maria Chiara; Sciammarella, Concetta; Ambrosio, Maria Rosaria; Bondanelli, Marta; Colao, Annamaria; Faggiano, Antongiulio

2018-01-01

Owing to the heterogeneity of neuroendocrine neoplasms (NENs), the availability of reliable circulating markers is critical for improving diagnostics, prognostic stratification, follow-up and definition of treatment strategy. This review is focused on chromogranin A (CgA), a hydrophilic glycoprotein present in large dense core vesicles of neuroendocrine cells. Despite being long identified as the most useful NEN-related circulating marker, clinical application of CgA is controversial. CgA assays still lack standardization, thus hampering not only clinical management but also the comparison between different analyses. In the diagnostic setting, clinical utility of CgA is limited as hampered by (a) the variety of oncological and non-oncological conditions affecting marker levels, which impairs specificity; (b) the fact that 30-50% of NENs show normal CgA, which impairs sensitivity. Regarding the prognostic phase, there is prospective evidence which demonstrates that advanced NENs secreting CgA have poorer outcome, as compared with those showing non-elevated marker levels. Although the identification of cut-offs allowing a proper risk stratification of CgA-secreting patients has not been performed, this represents the most important clinical application of the marker. By contrast, based on prospective studies, the trend of elevated circulating CgA does not represent a valid indicator of morphological evolution and has therefore no utility for the follow-up phase. Ultimately, current knowledge about the role of the marker for the definition of treatment strategy is poor and is limited by the small number of available studies, their prevalent retrospective nature and the absence of control groups of untreated subjects. © 2018 Society for Endocrinology.

Female nurses' burnout symptoms: No association with the Hypothalamic-pituitary-thyroid (HPT) axis.

PubMed

Guo, Yufang; Lam, Louisa; Luo, Yuanhui; Plummer, Virginia; Cross, Wendy; Li, Hui; Yin, Yizhen; Zhang, Jingping

2017-03-01

Across the world, hospital nurses experience a high level of burnout. Exploring biochemical markers of burnout could help to understand physiological changes and may provide useful evidence for preventing burnout symptoms. The current study included 94 female nurses from one Chinese third-level hospital. The Maslach Burnout Inventory-General Survey (MBI-GS) was used to investigate burnout symptoms: emotional exhaustion, cynicism, reduced professional efficacy, as well as the burnout average. The HPT axis was tested by checking blood levels of thyroid-stimulating hormone (TSH), thyroxin (T 4 ) and triiodothyronine (T 3 ). Nonparametric tests showed that no significant difference in biochemical markers was found between the burnout and non-burnout groups. Spearman correlation analysis found that biochemical markers had no significant association with burnout symptoms, except weakly negative associations between reduced professional efficacy and blood pressure and heart rate. These findings show a rather poor correlation of the HPT axis on burnout symptoms. Expanding the biochemical index of the HPT axis, comparing well-defined samples and using longitudinal studies are recommended for further studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neurocognitive markers of cognitive impairment: exploring the roles of speed and inconsistency.

PubMed

Dixon, Roger A; Garrett, Douglas D; Lentz, Tanya L; MacDonald, Stuart W S; Strauss, Esther; Hultsch, David F

2007-05-01

A well-known challenge for research in the cognitive neuropsychology of aging is to distinguish between the deficits and changes associated with normal aging and those indicative of early cognitive impairment. In a series of 2 studies, the authors explored whether 2 neurocognitive markers, speed (mean level) and inconsistency (intraindividual variability), distinguished between age groups (64-73 and 74-90+ years) and cognitive status groups (nonimpaired, mildly impaired, and moderately impaired). Study 1 (n = 416) showed that both level and inconsistency distinguished between the age and 2 cognitive status (not impaired, mildly impaired) groups, with a modest tendency for inconsistency to predict group membership over and above mean level. Study 2 (n = 304) replicated these results but extended them because of the qualifying effects associated with the unique moderately impaired oldest group. Specifically, not only were the groups more firmly distinguished by both indicators of speed, but evidence for the differential contribution of performance inconsistency was stronger. Neurocognitive markers of speed and inconsistency may be leading indicators of emerging cognitive impairment. (c) 2007 APA, all rights reserved

Epidermal stem cells: location, potential and contribution to cancer.

PubMed

Ambler, C A; Määttä, A

2009-01-01

Epidermal stem cells have been classically characterized as slow-cycling, long-lived cells that reside in discrete niches in the skin. Gene expression studies of niche-resident cells have revealed a number of stem cell markers and regulators, including the Wnt/beta-catenin, Notch, p63, c-Myc and Hedgehog pathways. A new study challenges the traditional developmental paradigm of slow-cycling stem cells and rapid-cycling transit amplifying cells in some epidermal regions, and there is mounting evidence to suggest that multi-lineage epidermal progenitors can be isolated from highly proliferative, non-niche regions. Whether there is a unique microenvironment surrounding these progenitors remains to be determined. Interestingly, cancer stem cells derived from epidermal tumours exist independent of the classic skin stem cell niche, yet also have stem cell properties, including multi-lineage differentiation. This review summarizes recent studies identifying the location and regulators of mouse and human epidermal stem cells and highlights the strategies used to identify cancer stem cells, including expression of normal epidermal stem cell markers, expression of cancer stem cell markers identified in other epidermal tumours and characterization of side-population tumour cells.

Spaceflight and the Mouse Eye: Results from Experiments on Shuttle Missions STS-133 and STS-135

NASA Technical Reports Server (NTRS)

Zanello, Susana B.; Theriot, Corey A.; Ponce, Claudia Prospero; Chevez-Barrios, Patricia

2013-01-01

Vision alterations associated with globe flattening, chorodial folds and papilledema, shown in some crew members returning from long duration missions. Hypothesis: Ocular neuroanatomical changes observed in the VIIP syndrome are accompanied by retinal changes at the molecular and cellular level that may affect retinal health and physiology. Objective: Investigate evidence of ocular (retinal) changes associated with spaceflight: (1) histological markers of cellular death and damage (2) molecular markers of oxidative stress (3) gene expression markers of stress

Vitamin B12 intake and status and cognitive function in elderly people.

PubMed

Doets, Esmée L; van Wijngaarden, Janneke P; Szczecińska, Anna; Dullemeijer, Carla; Souverein, Olga W; Dhonukshe-Rutten, Rosalie A M; Cavelaars, Adrienne E J M; van 't Veer, Pieter; Brzozowska, Anna; de Groot, Lisette C P G M

2013-01-01

Current recommendations on vitamin B12 intake vary from 1.4 to 3.0 μg per day and are based on the amount needed for maintenance of hematologic status or on the amount needed to compensate obligatory losses. This systematic review evaluates whether the relation between vitamin B12 intake and cognitive function should be considered for underpinning vitamin B12 recommendations in the future. The authors summarized dose-response evidence from randomized controlled trials and prospective cohort studies on the relation of vitamin B12 intake and status with cognitive function in adults and elderly people. Two randomized controlled trials and 6 cohort studies showed no association or inconsistent associations between vitamin B12 intake and cognitive function. Random-effects meta-analysis showed that serum/plasma vitamin B12 (50 pmol/L) was not associated with risk of dementia (4 cohort studies), global cognition z scores (4 cohort studies), or memory z scores (4 cohort studies). Although dose-response evidence on sensitive markers of vitamin B12 status (methylmalonic acid and holotranscobalamin) was scarce, 4 of 5 cohort studies reported significant associations with risk of dementia, Alzheimer's disease, or global cognition. Current evidence on the relation between vitamin B12 intake or status and cognitive function is not sufficient for consideration in the development of vitamin B12 recommendations. Further studies should consider the selection of sensitive markers of vitamin B12 status. © The Author 2012. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Atypical preference for infant-directed speech as an early marker of autism spectrum disorders? A literature review and directions for further research.

PubMed

Filipe, Marisa G; Watson, Linda; Vicente, Selene G; Frota, Sónia

2018-01-01

Autism spectrum disorders (ASD) refer to a complex group of neurodevelopmental disorders causing difficulties with communication and interpersonal relationships, as well as restricted and repetitive behaviours and interests. As early identification, diagnosis, and intervention provide better long-term outcomes, early markers of ASD have gained increased research attention. This review examines evidence that auditory processing enhanced by social interest, in particular auditory preference of speech directed towards infants and young children (i.e. infant-directed speech - IDS), may be an early marker of risk for ASD. Although this review provides evidence for IDS preference as, indeed, a potential early marker of ASD, the explanation for differences in IDS processing among children with ASD versus other children remains unclear, as are the implications of these impairments for later social-communicative development. Therefore, it is crucial to explore atypicalities in IDS processing early on development and to understand whether preferential listening to specific types of speech sounds in the first years of life may help to predict the impairments in social and language development.

A Metabolic Study of Huntington's Disease.

PubMed

Nambron, Rajasree; Silajdžić, Edina; Kalliolia, Eirini; Ottolenghi, Chris; Hindmarsh, Peter; Hill, Nathan R; Costelloe, Seán J; Martin, Nicholas G; Positano, Vincenzo; Watt, Hilary C; Frost, Chris; Björkqvist, Maria; Warner, Thomas T

2016-01-01

Huntington's disease patients have a number of peripheral manifestations suggestive of metabolic and endocrine abnormalities. We, therefore, investigated a number of metabolic factors in a 24-hour study of Huntington's disease gene carriers (premanifest and moderate stage II/III) and controls. Control (n = 15), premanifest (n = 14) and stage II/III (n = 13) participants were studied with blood sampling over a 24-hour period. A battery of clinical tests including neurological rating and function scales were performed. Visceral and subcutaneous adipose distribution was measured using magnetic resonance imaging. We quantified fasting baseline concentrations of glucose, insulin, cholesterol, triglycerides, lipoprotein (a), fatty acids, amino acids, lactate and osteokines. Leptin and ghrelin were quantified in fasting samples and after a standardised meal. We assessed glucose, insulin, growth hormone and cortisol concentrations during a prolonged oral glucose tolerance test. We found no highly significant differences in carbohydrate, protein or lipid metabolism markers between healthy controls, premanifest and stage II/III Huntington's disease subjects. For some markers (osteoprotegerin, tyrosine, lysine, phenylalanine and arginine) there is a suggestion (p values between 0.02 and 0.05) that levels are higher in patients with premanifest HD, but not moderate HD. However, given the large number of statistical tests performed interpretation of these findings must be cautious. Contrary to previous studies that showed altered levels of metabolic markers in patients with Huntington's disease, our study did not demonstrate convincing evidence of abnormalities in any of the markers examined. Our analyses were restricted to Huntington's disease patients not taking neuroleptics, anti-depressants or other medication affecting metabolic pathways. Even with the modest sample sizes studied, the lack of highly significant results, despite many being tested, suggests that the majority of these markers do not differ markedly by disease status.

Trend of different molecular markers in the last decades for studying human migrations.

PubMed

Kundu, Sharbadeb; Ghosh, Sankar Kumar

2015-02-10

Anatomically modern humans are known to have widely migrated throughout history. Different scientific evidences suggest that the entire human population descended from just several thousand African migrants. About 85,000 years ago, the first wave of human migration was out of Africa, that followed the coasts through the Middle East, into Southern Asia via Sri Lanka, and in due course around Indonesia and into Australia. Another wave of migration between 40,000 and 12,000 years ago brought humans northward into Europe. However, the frozen north limited human expansion in Europe, and created a land bridge, "Bering land bridge", connecting Asia with North America about 25,000 years ago. Although fossil data give the most direct information about our past, it has certain anomalies. So, molecular archeologists are now using different molecular markers to trace the "most recent common ancestor" and also the migration pattern of modern humans. In this study, we have studied the trend of molecular markers and also the methodologies implemented in the last decades (2003-2014). From our observation, we can say that D-loop region of mtDNA and Y chromosome based markers are predominant. Nevertheless, mtDNA, especially the D-loop region, has some unique features, which makes it a more effective marker for tracing prehistoric footprints of modern human populations. Although, natural selection should also be taken into account in studying mtDNA based human migration. As per technology is concerned, Sanger sequencing is the major technique that is being used in almost all studies. But, the emergence of different cost-effective-and-easy-to-handle NGS platforms has increased its popularity over Sanger sequencing in studying human migration. Copyright © 2014. Published by Elsevier B.V.

Chronic inflammation and risk of colorectal and other obesity-related cancers: The health, aging and body composition study.

PubMed

Izano, Monika; Wei, Esther K; Tai, Caroline; Swede, Helen; Gregorich, Steven; Harris, Tamara B; Klepin, Heidi; Satterfield, Suzanne; Murphy, Rachel; Newman, Anne B; Rubin, Susan M; Braithwaite, Dejana

2016-03-01

Evidence of the association between chronic inflammation and the risk of colorectal cancer (CRC) and other obesity-related cancers (OBRC) remains inconsistent, possibly due to a paucity of studies examining repeated measures of inflammation. In the Health ABC prospective study of 2,490 adults aged 70-79 years at baseline, we assessed whether circulating levels of three markers of systemic inflammation, IL-6, CRP and TNF-α, were associated with the risk of CRC and OBRC, a cluster including cancers of pancreas, prostate, breast and endometrium. Inflammatory markers were measured in stored fasting blood samples. While only baseline measures of TNF-α were available, IL-6 and CRP were additionally measured at Years 2, 4, 6 and 8. Multivariable Cox models were fit to determine whether tertiles and log-transformed baseline, updated and averaged measures of CRP and IL-6 and baseline measures of TNF-α were associated with the risk of incident cancer(s). During a median follow-up of 11.9 years, we observed 55 and 172 cases of CRC and OBRC, respectively. The hazard of CRC in the highest tertile of updated CRP was more than double that in the lowest tertile (HR = 2.29; 95% CI: 1.08-4.86). No significant associations were seen between colorectal cancer and IL-6 or TNF-α. Additionally, no significant associations were found between obesity-related cancers and the three inflammatory markers overall, but we observed a suggestion of effect modification by BMI and NSAID use. In summary, in this population, higher CRP levels were associated with increased risk of CRC, but not of OBRC. The findings provide new evidence that chronically elevated levels of CRP, as reflected by repeated measures of this marker, may play a role in colorectal carcinogenesis in older adults. © 2015 UICC.

Cardiovascular benefits of lycopene: fantasy or reality?

PubMed

Thies, Frank; Mills, Lynsey M; Moir, Susan; Masson, Lindsey F

2017-05-01

Epidemiological evidence indicates that high consumption of tomatoes and tomato-based products reduces the risk of chronic diseases such as CVD and cancer. Such potential benefits are often ascribed to high concentrations of lycopene present in tomato products. Mainly from the results of in vitro studies, potential biological mechanisms by which carotenoids could protect against heart disease and cancer have been suggested. These include cholesterol reduction, inhibition of oxidation processes, modulation of inflammatory markers, enhanced intercellular communication, inhibition of tumourigenesis and induction of apoptosis, metabolism to retinoids and antiangiogenic effects. However, with regard to CVD, results from intervention studies gave mixed results. Over fifty human intervention trials with lycopene supplements or tomato-based products have been conducted to date, the majority being underpowered. Many showed some beneficial effects but mostly on non-established cardiovascular risk markers such as lipid peroxidation, DNA oxidative damage, platelet activation and inflammatory markers. Only a few studies showed improvement in lipid profiles, C reactive protein and blood pressure. However, recent findings indicate that lycopene could exert cardiovascular protection by lowering HDL-associated inflammation, as well as by modulating HDL functionality towards an antiatherogenic phenotype. Furthermore, in vitro studies indicate that lycopene could modulate T lymphocyte activity, which would also inhibit atherogenic processes and confer cardiovascular protection. These findings also suggest that HDL functionality deserves further consideration as a potential early marker for CVD risk, modifiable by dietary factors such as lycopene.

Association Analysis Suggests SOD2 as a Newly Identified Candidate Gene Associated With Leprosy Susceptibility.

PubMed

Ramos, Geovana Brotto; Salomão, Heloisa; Francio, Angela Schneider; Fava, Vinícius Medeiros; Werneck, Renata Iani; Mira, Marcelo Távora

2016-08-01

Genetic studies have identified several genes and genomic regions contributing to the control of host susceptibility to leprosy. Here, we test variants of the positional and functional candidate gene SOD2 for association with leprosy in 2 independent population samples. Family-based analysis revealed an association between leprosy and allele G of marker rs295340 (P = .042) and borderline evidence of an association between leprosy and alleles C and A of markers rs4880 (P = .077) and rs5746136 (P = .071), respectively. Findings were validated in an independent case-control sample for markers rs295340 (P = .049) and rs4880 (P = .038). These results suggest SOD2 as a newly identified gene conferring susceptibility to leprosy. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Dose-response relationships in multifunctional food design: assembling the evidence.

PubMed

Aggett, Peter J

2012-03-01

Demonstrating single and multiple functions attributable to foods or specific food components is a challenge. The International Life Sciences Institute Europe co-ordinated EU concerted actions, Functional Food Science in Europe (FUFOSE) and the Process for the Assessment of Scientific Support for Claims on Food (PASSCLAIM), respectively, addressed the soundness of the evidence and its coherence with a mechanistic schema comprising valid markers of exposure, intermediate and final outcomes and the quality and integrity of the evidence overall. Demonstrating causality often relies on randomized controlled trials (RCTs). However, in public health and biomedical science there is concern about the suitability of RCTs as sole standards of evidence-based approaches. Alternative and complementary approaches using updated Hill's viewpoints for appraising the evidence can be used in conjunction with evidence-based mechanistic reasoning and the quality criteria proposed in FUFOSE and PASSCLAIM to design studies and to assemble evidence exploring single or multiple benefits from food components and foods.

Further linkage evidence for localization of mutational sites for nonsyndromic types of X-linked mental retardation at pericentromeric region

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

Robledo, R.; Melis, P.; Siniscalco, M.

We used several microsatellite markers scattered along the X chromosome to search for linkage relationships in a large Sardinian pedigree segregating for nonspecific X-linked mental retardation (MRX). Markers DXS573 and AR, located at chromosomal subregions Xp11.4-p11.22 and Xq11.2-q12, respectively, were found to segregate in full concordance with the disease, leading to a LOD score of 4.21 at zero recombination value. Recombination with the disease was found with markers MAOB and DXS454 located at Xp11.4-p11.3 and Xq21.1-q22, respectively; accordingly, markers distal to Xp11.4 and Xq22 also segregated independently of the disease. These findings provide strong linkage evidence in favor of themore » localization of one MRX mutational site in the pericentromeric region of the human X chromosome, justifying the assignment of a new symbol (MRX26) to our pedigree. Finally, on the basis of the recombinational events observed in the Xq21-q22 region, we have been able to refine the assignment of marker DXS456 to Xq21.33-q22. 26 refs., 3 figs., 1 tab.« less

Using host-associated genetic markers to investigate sources of fecal contamination in two Vermont streams

USGS Publications Warehouse

Medalie, Laura; Matthews, Leslie J.; Stelzer, Erin A.

2011-01-01

The use of host-associated Bacteroidales-based 16S ribosomal ribonucleic acid genetic markers was investigated as a tool for providing information to managers on sources of bacterial impairment in Vermont streams. The study was conducted during 2009 in two watersheds on the U.S. Environmental Protection Agency's 303(d) List of Impaired Waters, the Huntington and the Mettawee Rivers. Streamwater samples collected during high-flow and base-flow conditions were analyzed for concentrations of Escherichia coli (E. coli) and Bacteroidales genetic markers (General AllBac, Human qHF183 and BacHum, Ruminant BoBac, and Canid BacCan) to identify humans, ruminants, and canids as likely or unlikely major sources of fecal contamination. Fecal reference samples from each of the potential source groups, as well as from common species of wildlife, were collected during the same season and from the same watersheds as water samples. The results were combined with data from other states to assess marker cross reaction and to relate marker results to E. coli, the regulated water-quality parameter, with a higher degree of statistical significance. Results from samples from the Huntington River collected under different flow conditions on three dates indicated that humans were unlikely to be a major source of fecal contamination, except for a single positive result at one station that indicated the potential for human sources. Ruminants (deer, moose, cow, or sheep) were potential sources of fecal contamination at all six stations on the Huntington River during one high-flow event and at all but two stations during the other high-flow event. Canids were potential sources of fecal contamination at some stations during two high-flow events, with genetic-marker concentrations in samples from two of the six stations showing consistent positive results for canids for both storm dates. A base-flow sample showed no evidence of major fecal contamination in the Huntington River from humans, ruminants, or canids. Results from samples from the Mettawee River watershed collected during high-flow conditions (12 storm samples on 2 dates at 6 stations) indicated that there was no evidence of fecal contamination from humans in seven samples and possible evidence in five samples. Results for humans were positive for only one station during both storm events. For two of the five samples with evidence for human fecal contamination, results for two different human genetic markers agreed, but results from three samples were inconsistent. In samples from five of the six Mettawee stations, ruminants were a potential source of fecal contamination on at least one of the three sampled dates, including three positive results for the base-flow sample. Yet samples from all of the stations that showed positive results for ruminants did so for only one or two of the three sampled dates. Samples from only one of the six stations gave consistent results, which were negative for ruminants for all three dates. In the Mettawee River base-flow sample, humans were an unlikely source of major fecal contamination. Factors that may influence results and conclusions include the timing of sample collection relative to the storm event; variability of E. coli and Bacteroidales concentrations in fecal reference samples and in water; sampling and analytical errors; the potential cross reactivity of host-associated genetic markers; and different persistence and survival rates of E. coli bacteria and Bacteroidales genetic markers on land, in water, and by season. These factors interfere with the ability to directly relate Bacteroidales concentrations to E. coli concentrations in river samples. It must be recognized that while use of Bacteroidales genetic markers as a source tracking tool coupled with the interpretive approach described in this report cannot be used quantitatively to pinpoint sources, it can be used to exclude potential sources as major contributors to fecal contamination.

Evolving Evidence for the Value of Neuroimaging Methods and Biological Markers in Subjects Categorized with Subjective Cognitive Decline.

PubMed

Lista, Simone; Molinuevo, Jose L; Cavedo, Enrica; Rami, Lorena; Amouyel, Philippe; Teipel, Stefan J; Garaci, Francesco; Toschi, Nicola; Habert, Marie-Odile; Blennow, Kaj; Zetterberg, Henrik; O'Bryant, Sid E; Johnson, Leigh; Galluzzi, Samantha; Bokde, Arun L W; Broich, Karl; Herholz, Karl; Bakardjian, Hovagim; Dubois, Bruno; Jessen, Frank; Carrillo, Maria C; Aisen, Paul S; Hampel, Harald

2015-09-24

There is evolving evidence that individuals categorized with subjective cognitive decline (SCD) are potentially at higher risk for developing objective and progressive cognitive impairment compared to cognitively healthy individuals without apparent subjective complaints. Interestingly, SCD, during advancing preclinical Alzheimer's disease (AD), may denote very early, subtle cognitive decline that cannot be identified using established standardized tests of cognitive performance. The substantial heterogeneity of existing SCD-related research data has led the Subjective Cognitive Decline Initiative (SCD-I) to accomplish an international consensus on the definition of a conceptual research framework on SCD in preclinical AD. In the area of biological markers, the cerebrospinal fluid signature of AD has been reported to be more prevalent in subjects with SCD compared to healthy controls; moreover, there is a pronounced atrophy, as demonstrated by magnetic resonance imaging, and an increased hypometabolism, as revealed by positron emission tomography, in characteristic brain regions affected by AD. In addition, SCD individuals carrying an apolipoprotein ɛ4 allele are more likely to display AD-phenotypic alterations. The urgent requirement to detect and diagnose AD as early as possible has led to the critical examination of the diagnostic power of biological markers, neurophysiology, and neuroimaging methods for AD-related risk and clinical progression in individuals defined with SCD. Observational studies on the predictive value of SCD for developing AD may potentially be of practical value, and an evidence-based, validated, qualified, and fully operationalized concept may inform clinical diagnostic practice and guide earlier designs in future therapy trials.

Effects of nutritional supplementation during pregnancy on early adult disease risk: follow up of offspring of participants in a randomised controlled trial investigating effects of supplementation on infant birth weight.

PubMed

Macleod, John; Tang, Lie; Hobbs, F D Richard; Wharton, Brian; Holder, Roger; Hussain, Shakir; Nichols, Linda; Stewart, Paul; Clark, Penny; Luzio, Steve; Holly, Jeff; Smith, George Davey

2013-01-01

Observational evidence suggests that improving fetal growth may improve adult health. Experimental evidence from nutritional supplementation trials undertaken amongst pregnant women in the less developed world does not show strong or consistent effects on adult disease risk and no trials from the more developed world have previously been reported. To test the hypothesis that nutritional supplementation during pregnancy influences offspring disease risk in adulthood. Clinical assessment of a range of established diseases risk markers in young adult offspring of 283 South Asian mothers who participated in two trials of nutritional supplementation during pregnancy (protein/energy/vitamins; energy/vitamins or vitamins only) at Sorrento Maternity Hospital in Birmingham UK either unselected or selected on the basis of nutritional status. 236 (83%) offspring were traced and 118 (50%) of these were assessed in clinic. Protein/energy/vitamins supplementation amongst undernourished mothers was associated with increased infant birthweight. Nutritional supplementation showed no strong association with any one of a comprehensive range of markers of adult disease risk and no consistent pattern of association with risk across markers in offspring of either unselected or undernourished mothers. We found no evidence that nutritional supplements given to pregnant women are an important influence on adult disease risk however our study lacked power to estimate small effects. Our findings do not provide support for a policy of nutritional supplementation for pregnant women as an effective means to improve adult health in more developed societies.

Quantitative Comparison and Metabolite Profiling of Saponins in Different Parts of the Root of Panax notoginseng

PubMed Central

2015-01-01

Although both rhizome and root of Panax notoginseng are officially utilized as notoginseng in “Chinese Pharmacopoeia”, individual parts of the root were differently used in practice. To provide chemical evidence for the differentiated usage, quantitative comparison and metabolite profiling of different portions derived from the whole root, as well as commercial samples, were carried out, showing an overall higher content of saponins in rhizome, followed by main root, branch root, and fibrous root. Ginsenoside Rb2 was proposed as a potential marker with a content of 0.5 mg/g as a threshold value for differentiating rhizome from other parts. Multivariate analysis of the metabolite profile further suggested 32 saponins as potential markers for the discrimination of different parts of notoginseng. Collectively, the study provided comprehensive chemical evidence for the distinct usage of different parts of notoginseng and, hence, is of great importance for the rational application and exploitation of individual parts of notoginseng. PMID:25118819

Do dominant and non-dominant arms respond similarly to maximal eccentric exercise of the elbow flexors?

PubMed

Newton, Michael J; Sacco, Paul; Chapman, Dale; Nosaka, Kazunori

2013-03-01

Two common models to investigate the effect of interventions on muscle damage include using two groups in which one group receives an intervention while the other acts as control, and using contralateral limbs of one group. The latter model is based on the assumption that changes in markers of muscle damage are similar between limbs, but this has not been examined systematically. This study compared changes in muscle damage markers between dominant and non-dominant arms following maximal eccentric exercise of the elbow flexors. Eighteen men performed 60 maximal eccentric elbow flexions of each arm separated by 4 weeks with the order of testing between arms randomised. Maximal voluntary isometric torque, range of motion, upper arm circumference, plasma creatine kinase (CK) activity and muscle soreness before and for 7 days following exercise were compared between arms using two-way repeated measures ANOVA. No significant differences between arms were evident for any of the markers, but significant (P<0.05) differences between first and second bouts were evident for changes in strength, circumference and CK with smaller changes following the second bout. A poor correlation was found for the magnitude of changes in the markers between dominant and non-dominant arms, suggesting that responses to eccentric exercise were not necessarily the same between arms. These results show that the order affected the responses of dominant and non-dominant arms to the eccentric exercise; however, the contralateral limb design appears to be usable if bout order is counterbalanced and randomised among participants. Copyright © 2012. Published by Elsevier Ltd.

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.

Impact of physical activity, cardiorespiratory fitness, and exercise training on markers of inflammation.

PubMed

Lavie, Carl J; Church, Timothy S; Milani, Richard V; Earnest, Conrad P

2011-01-01

Physical activity and exercise training (ET) enhance overall cardiorespiratory fitness (ie, fitness), thus producing many benefits in the primary and secondary prevention of cardiovascular diseases. Substantial evidence also indicates that acute and chronic inflammation is involved in the development and progression of atherosclerosis and major cardiovascular events. The most commonly utilized marker of inflammation is C-reactive protein (CRP). In this review, we discuss the importance of inflammation, especially CRP, as a cardiovascular risk marker by reviewing an abundant cross-sectional and clinical intervention literature providing evidence that physical activity, enhanced fitness, and ET are inversely associated with CRP and that being overweight or obese is directly related with inflammation/CRP. Although we discuss the controversy regarding whether or not ET reduces CRP independent of weight loss, clearly physical activity, improved fitness, and ET are associated with reductions in inflammation and overall cardiovascular risk in both primary and secondary prevention.

A genomewide screen for late-onset Alzheimer disease in a genetically isolated Dutch population.

PubMed

Liu, Fan; Arias-Vásquez, Alejandro; Sleegers, Kristel; Aulchenko, Yurii S; Kayser, Manfred; Sanchez-Juan, Pascual; Feng, Bing-Jian; Bertoli-Avella, Aida M; van Swieten, John; Axenovich, Tatiana I; Heutink, Peter; van Broeckhoven, Christine; Oostra, Ben A; van Duijn, Cornelia M

2007-07-01

Alzheimer disease (AD) is the most common cause of dementia. We conducted a genome screen of 103 patients with late-onset AD who were ascertained as part of the Genetic Research in Isolated Populations (GRIP) program that is conducted in a recently isolated population from the southwestern area of The Netherlands. All patients and their 170 closely related relatives were genotyped using 402 microsatellite markers. Extensive genealogy information was collected, which resulted in an extremely large and complex pedigree of 4,645 members. The pedigree was split into 35 subpedigrees, to reduce the computational burden of linkage analysis. Simulations aiming to evaluate the effect of pedigree splitting on false-positive probabilities showed that a LOD score of 3.64 corresponds to 5% genomewide type I error. Multipoint analysis revealed four significant and one suggestive linkage peaks. The strongest evidence of linkage was found for chromosome 1q21 (heterogeneity LOD [HLOD]=5.20 at marker D1S498). Approximately 30 cM upstream of this locus, we found another peak at 1q25 (HLOD=4.0 at marker D1S218). These two loci are in a previously established linkage region. We also confirmed the AD locus at 10q22-24 (HLOD=4.15 at marker D10S185). There was significant evidence of linkage of AD to chromosome 3q22-24 (HLOD=4.44 at marker D3S1569). For chromosome 11q24-25, there was suggestive evidence of linkage (HLOD=3.29 at marker D11S1320). We next tested for association between cognitive function and 4,173 single-nucleotide polymorphisms in the linked regions in an independent sample consisting of 197 individuals from the GRIP region. After adjusting for multiple testing, we were able to detect significant associations for cognitive function in four of five AD-linked regions, including the new region on chromosome 3q22-24 and regions 1q25, 10q22-24, and 11q25. With use of cognitive function as an endophenotype of AD, our study indicates the that the RGSL2, RALGPS2, and C1orf49 genes are the potential disease-causing genes at 1q25. Our analysis of chromosome 10q22-24 points to the HTR7, MPHOSPH1, and CYP2C cluster. This is the first genomewide screen that showed significant linkage to chromosome 3q23 markers. For this region, our analysis identified the NMNAT3 and CLSTN2 genes. Our findings confirm linkage to chromosome 11q25. We were unable to confirm SORL1; instead, our analysis points to the OPCML and HNT genes.

Spatial Relationships between Markers for Secretory and Endosomal Machinery in Human Cytomegalovirus-Infected Cells versus Those in Uninfected Cells▿†

PubMed Central

Das, Subhendu; Pellett, Philip E.

2011-01-01

Human cytomegalovirus (HCMV) induces extensive remodeling of the secretory apparatus to form the cytoplasmic virion assembly compartment (cVAC), where virion tegumentation and envelopment take place. We studied the structure of the cVAC by confocal microscopy to assess the three-dimensional distribution of proteins specifically associated with individual secretory organelles. In infected cells, early endosome antigen 1 (EEA1)-positive vesicles are concentrated at the center of the cVAC and, as previously seen, are distinct from structures visualized by markers for the endoplasmic reticulum, Golgi apparatus, and trans-Golgi network (TGN). EEA1-positive vesicles can be strongly associated with markers for recycling endosomes, to a lesser extent with markers associated with components of the endosomal sorting complex required for transport III (ESCRT III) machinery, and then with markers of late endosomes. In comparisons of uninfected and infected cells, we found significant changes in the structural associations and colocalization of organelle markers, as well as in net organelle volumes. These results provide new evidence that the HCMV-induced remodeling of the membrane transport apparatus involves much more than simple relocation and expansion of preexisting structures and are consistent with the hypothesis that the shift in identity of secretory organelles in HCMV-infected cells results in new functional profiles. PMID:21471245

Pupil dilation signals uncertainty and surprise in a learning gambling task.

PubMed

Lavín, Claudio; San Martín, René; Rosales Jubal, Eduardo

2013-01-01

Pupil dilation under constant illumination is a physiological marker where modulation is related to several cognitive functions involved in daily decision making. There is evidence for a role of pupil dilation change during decision-making tasks associated with uncertainty, reward-prediction errors and surprise. However, while some work suggests that pupil dilation is mainly modulated by reward predictions, others point out that this marker is related to uncertainty signaling and surprise. Supporting the latter hypothesis, the neural substrate of this marker is related to noradrenaline (NA) activity which has been also related to uncertainty signaling. In this work we aimed to test whether pupil dilation is a marker for uncertainty and surprise in a learning task. We recorded pupil dilation responses in 10 participants performing the Iowa Gambling Task (IGT), a decision-making task that requires learning and constant monitoring of outcomes' feedback, which are important variables within the traditional study of human decision making. Results showed that pupil dilation changes were modulated by learned uncertainty and surprise regardless of feedback magnitudes. Interestingly, greater pupil dilation changes were found during positive feedback (PF) presentation when there was lower uncertainty about a future negative feedback (NF); and by surprise during NF presentation. These results support the hypothesis that pupil dilation is a marker of learned uncertainty, and may be used as a marker of NA activity facing unfamiliar situations in humans.

Pupil dilation signals uncertainty and surprise in a learning gambling task

PubMed Central

Lavín, Claudio; San Martín, René; Rosales Jubal, Eduardo

2014-01-01

Pupil dilation under constant illumination is a physiological marker where modulation is related to several cognitive functions involved in daily decision making. There is evidence for a role of pupil dilation change during decision-making tasks associated with uncertainty, reward-prediction errors and surprise. However, while some work suggests that pupil dilation is mainly modulated by reward predictions, others point out that this marker is related to uncertainty signaling and surprise. Supporting the latter hypothesis, the neural substrate of this marker is related to noradrenaline (NA) activity which has been also related to uncertainty signaling. In this work we aimed to test whether pupil dilation is a marker for uncertainty and surprise in a learning task. We recorded pupil dilation responses in 10 participants performing the Iowa Gambling Task (IGT), a decision-making task that requires learning and constant monitoring of outcomes’ feedback, which are important variables within the traditional study of human decision making. Results showed that pupil dilation changes were modulated by learned uncertainty and surprise regardless of feedback magnitudes. Interestingly, greater pupil dilation changes were found during positive feedback (PF) presentation when there was lower uncertainty about a future negative feedback (NF); and by surprise during NF presentation. These results support the hypothesis that pupil dilation is a marker of learned uncertainty, and may be used as a marker of NA activity facing unfamiliar situations in humans. PMID:24427126

Continental-scale footprint of balancing and positive selection in a small rodent (Microtus arvalis).

PubMed

Fischer, Martin C; Foll, Matthieu; Heckel, Gerald; Excoffier, Laurent

2014-01-01

Genetic adaptation to different environmental conditions is expected to lead to large differences between populations at selected loci, thus providing a signature of positive selection. Whereas balancing selection can maintain polymorphisms over long evolutionary periods and even geographic scale, thus leads to low levels of divergence between populations at selected loci. However, little is known about the relative importance of these two selective forces in shaping genomic diversity, partly due to difficulties in recognizing balancing selection in species showing low levels of differentiation. Here we address this problem by studying genomic diversity in the European common vole (Microtus arvalis) presenting high levels of differentiation between populations (average F ST = 0.31). We studied 3,839 Amplified Fragment Length Polymorphism (AFLP) markers genotyped in 444 individuals from 21 populations distributed across the European continent and hence over different environmental conditions. Our statistical approach to detect markers under selection is based on a Bayesian method specifically developed for AFLP markers, which treats AFLPs as a nearly codominant marker system, and therefore has increased power to detect selection. The high number of screened populations allowed us to detect the signature of balancing selection across a large geographic area. We detected 33 markers potentially under balancing selection, hence strong evidence of stabilizing selection in 21 populations across Europe. However, our analyses identified four-times more markers (138) being under positive selection, and geographical patterns suggest that some of these markers are probably associated with alpine regions, which seem to have environmental conditions that favour adaptation. We conclude that despite favourable conditions in this study for the detection of balancing selection, this evolutionary force seems to play a relatively minor role in shaping the genomic diversity of the common vole, which is more influenced by positive selection and neutral processes like drift and demographic history.

Peculiarities in the Gestural Repertoire: An Early Marker for Rett Syndrome?

ERIC Educational Resources Information Center

Marschik, Peter B.; Sigafoos, Jeff; Kaufmann, Walter E.; Wolin, Thomas; Talisa, Victor B.; Bartl-Pokorny, Katrin D.; Budimirovic, Dejan B.; Vollmann, Ralf; Einspieler, Christa

2012-01-01

We studied the gestures used by children with classic Rett syndrome (RTT) to provide evidence as to how this essential aspect of communicative functions develops. Seven participants with RTT were longitudinally observed between 9 and 18 months of life. The gestures used by these participants were transcribed and coded from a retrospective analysis…

Persistent Angiogenesis in the Autism Brain: An Immunocytochemical Study of Postmortem Cortex, Brainstem and Cerebellum

ERIC Educational Resources Information Center

Azmitia, E. C.; Saccomano, Z. T.; Alzoobaee, M. F.; Boldrini, M.; Whitaker-Azmitia, P. M.

2016-01-01

In the current work, we conducted an immunocytochemical search for markers of ongoing neurogenesis (e.g. nestin) in auditory cortex from postmortem sections of autism spectrum disorder (ASD) and age-matched control donors. We found nestin labeling in cells of the vascular system, indicating blood vessels plasticity. Evidence of angiogenesis was…

Autonomy and Children's Reactions to Being Controlled: Evidence that Both Compliance and Defiance May Be Positive Markers in Early Development

ERIC Educational Resources Information Center

Dix, Theodore; Stewart, Amanda D.; Gershoff, Elizabeth T.; Day, William H.

2007-01-01

This study examined reactions of 1-year-olds and young 2-year-olds to being controlled by mothers. Mothers' supportive behavior predicted children's willing compliance. However, contrary to research with older children, defiance was also associated with variables linked to maternal competence, specifically, mothers' supportive behavior,…

Bottomless barrel-sponge species in the Indo-Pacific?

PubMed

Setiawan, Edwin; Voogd, Nicole J De; Wörheide, Gert; Erpenbeck, Dirk

2016-07-06

The use of nuclear markers, in addition to traditional mitochondrial markers, helps to clarify hidden patterns of genetic structure in natural populations (Palumbi & Baker, 1994). This is particularly evident among demosponges that possess slow mitochondrial evolutionary rates compared to Bilateria, where nuclear intron markers can aid in the understanding of shallow level phylogenetic relationships (Shearer et al., 2002). Ideally, these nuclear markers (i) are evolutionary well-conserved across different lineages, (ii) produce amplicons holding a number of sites with sufficient variability to answer the relevant phylogenetic question, (iii) derive from single copy genes (see review in Zhang & Hewitt, 2003). A popular method to amplify intron markers uses EPIC (Exon-Primed, Intron-Crossing) primers that anneal to the more conserved flanking exon regions and subsequently bridge the intron during amplification (Palumbi & Baker, 1994).

Exploring Cross-Linguistic Vocabulary Effects on Brain Structures Using Voxel-Based Morphometry

ERIC Educational Resources Information Center

Green, David W.; Crinion, Jenny; Price, Cathy J.

2007-01-01

Given that there are neural markers for the acquisition of a non-verbal skill, we review evidence of neural markers for the acquisition of vocabulary. Acquiring vocabulary is critical to learning one's native language and to learning other languages. Acquisition requires the ability to link an object concept (meaning) to sound. Is there a region…

Toward Tense as a Clinical Marker of Specific Language Impairment in English-Speaking Children.

ERIC Educational Resources Information Center

Rice, Mabel L.; Wexler, Kenneth

1996-01-01

Comparison of the speech of 37 preschool children with speech-language impairment (SLI), 40 language-matched children, and 45 age-matched children found that errors in a set of morphemes marking tense characterized the SLI children. Evidence supporting the use of these morphemes as clinical markers for SLI is offered. (DB)

ADRA2A is involved in neuro-endocrine regulation of bone resorption

PubMed Central

Mlakar, Vid; Jurkovic Mlakar, Simona; Zupan, Janja; Komadina, Radko; Prezelj, Janez; Marc, Janja

2015-01-01

Adrenergic stimulation is important for osteoclast differentiation and bone resorption. Previous research shows that this happens through β2-adrenergic receptor (AR), but there are conflicting evidence on presence and role of α2A-AR in bone. The aim of this study was to investigate the presence of α2A-AR and its involvement in neuro-endocrine signalling of bone remodelling in humans. Real-time polymerase chain reaction (PCR) and immunohistochemistry were used to investigate α2A-AR receptor presence and localization in bone cells. Functionality of rs553668 and rs1800544 single nucleotide polymorphism SNPs located in α2A-AR gene was analysed by qPCR expression on bone samples and luciferase reporter assay in human osteosarcoma HOS cells. Using real-time PCR, genetic association study between rs553668 A>G and rs1800544 C>G SNPs and major bone markers was performed on 661 Slovenian patients with osteoporosis. α2A-AR is expressed in osteoblasts and lining cells but not in osteocytes. SNP rs553668 has a significant influence on α2A-AR mRNA level in human bone samples through the stability of mRNA. α2A-AR gene locus associates with important bone remodelling markers (BMD, CTX, Cathepsin K and pOC). The results of this study are providing comprehensive new evidence that α2A-AR is involved in neuro-endocrine signalling of bone turnover and development of osteoporosis. As shown by our results the neurological signalling is mediated through osteoblasts and result in bone resorption. Genetic study showed association of SNPs in α2A-AR gene locus with bone remodelling markers, identifying the individuals with higher risk of development of osteoporosis. PMID:25818344

Demonstration of vesicular glutamate transporter-1 in corticotroph cells in the anterior pituitary of the rat.

PubMed

Kocsis, Zsuzsa S; Molnár, Csilla S; Watanabe, Masahiko; Daneels, Guy; Moechars, Dieder; Liposits, Zsolt; Hrabovszky, Erik

2010-02-01

Recent immunohistochemical studies of the rat adenohypophysis identified type-2 vesicular glutamate transporter (VGLUT2), a marker for glutamatergic neuronal phenotype, in high percentages of adenohypophysial gonadotrophs and thyrotrophs. The presence and molecular identity of amino acid neurotransmitters in the remaining hormone producing cell types are unknown. In the present study we addressed the putative synthesis of another glutamatergic marker, VGLUT1 by adenohypophysial cells. Immunohistochemical studies revealed VGLUT1 immunoreactivity in a small subset of polygonal medium-sized cells in the anterior lobe. Western blot analysis revealed a single major 60 kDa protein band in the adenohypophysis. Furthermore, the expression of VGLUT1 mRNA was confirmed by reverse transcription-polymerase chain reaction followed by sequence analysis of the amplicon. In contrast with rats which only showed VGLUT1 signal in the anterior lobe of the pituitary, mice contained high levels of VGLUT1 immunoreactivity in the intermediate, in addition to the anterior lobe. No signal was present in VGLUT1-knockout mice, providing evidence for specificity. In rats, results of colocalization studies with dual-immunofluorescent labeling provided evidence for VGLUT1 immunoreactivity in 45.9% of corticotrophs and 7.7% of luteinizing hormone beta-immunopositive gonadotrophs. Cells of the other peptide hormone phenotypes were devoid of VGLUT1 signal. A few cells in the adenohypophysis expressed both VGLUT1 and VGLUT2 immunoreactivities. The presence of the glutamate markers VGLUT1 and VGLUT2 in distinct populations of peptide hormone-secreting hypophysial cells highly indicates the involvement of endogenous glutamate release in autocrine/paracrine regulatory mechanisms. The biological function of adenohypophysial glutamate will require clarification. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Toolbox Approaches Using Molecular Markers and 16S rRNA Gene Amplicon Data Sets for Identification of Fecal Pollution in Surface Water

PubMed Central

Staley, C.; Sadowsky, M. J.; Gyawali, P.; Sidhu, J. P. S.; Palmer, A.; Beale, D. J.; Toze, S.

2015-01-01

In this study, host-associated molecular markers and bacterial 16S rRNA gene community analysis using high-throughput sequencing were used to identify the sources of fecal pollution in environmental waters in Brisbane, Australia. A total of 92 fecal and composite wastewater samples were collected from different host groups (cat, cattle, dog, horse, human, and kangaroo), and 18 water samples were collected from six sites (BR1 to BR6) along the Brisbane River in Queensland, Australia. Bacterial communities in the fecal, wastewater, and river water samples were sequenced. Water samples were also tested for the presence of bird-associated (GFD), cattle-associated (CowM3), horse-associated, and human-associated (HF183) molecular markers, to provide multiple lines of evidence regarding the possible presence of fecal pollution associated with specific hosts. Among the 18 water samples tested, 83%, 33%, 17%, and 17% were real-time PCR positive for the GFD, HF183, CowM3, and horse markers, respectively. Among the potential sources of fecal pollution in water samples from the river, DNA sequencing tended to show relatively small contributions from wastewater treatment plants (up to 13% of sequence reads). Contributions from other animal sources were rarely detected and were very small (<3% of sequence reads). Source contributions determined via sequence analysis versus detection of molecular markers showed variable agreement. A lack of relationships among fecal indicator bacteria, host-associated molecular markers, and 16S rRNA gene community analysis data was also observed. Nonetheless, we show that bacterial community and host-associated molecular marker analyses can be combined to identify potential sources of fecal pollution in an urban river. This study is a proof of concept, and based on the results, we recommend using bacterial community analysis (where possible) along with PCR detection or quantification of host-associated molecular markers to provide information on the sources of fecal pollution in waterways. PMID:26231650

Can Nucleoli Be Markers of Developmental Potential in Human Zygotes?

PubMed

Fulka, Helena; Kyogoku, Hirohisa; Zatsepina, Olga; Langerova, Alena; Fulka, Josef

2015-11-01

In 1999, Tesarik and Greco reported that they could predict the developmental potential of human zygotes from a single static evaluation of their pronuclei. This was based on the distribution and number of specific nuclear organelles - the nucleoli. Recent studies in mice show that nucleoli play a key role in parental genome restructuring after fertilization, and that interfering with this process may lead to developmental failure. These studies thus support the Tesarik-Greco evaluation as a potentially useful method for selecting high-quality embryos in human assisted reproductive technologies. In this opinion article we discuss recent evidence linking nucleoli to parental genome reprogramming, and ask whether nucleoli can mirror or be used as representative markers of embryonic parameters such as chromosome content or DNA fragmentation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Extended Intermarker Linkage Disequilibrium in the Afrikaners

PubMed Central

Hall, Diana; Wijsman, Ellen M.; Roos, J. Louw; Gogos, Joseph A.; Karayiorgou, Maria

2002-01-01

In this study we conducted an investigation of the background level of linkage disequilibrium (LD) in the Afrikaner population to evaluate the appropriateness of this genetic isolate for mapping complex traits. We analyzed intermarker LD in 62 nuclear families using microsatellite markers covering extended chromosomal regions. The markers were selected to allow the first direct comparison of long-range LD in the Afrikaners to LD in other demographic groups. Using several statistical measures, we find significant evidence for LD in the Afrikaners extending remarkably over a 6-cM range. In contrast, LD decays significantly beyond 3-cM distances in the other founder and outbred populations examined. This study strongly supports the appropriateness of the Afrikaner population for genome-wide scans that exploit LD to map common, multigenic disorders. PMID:12045148

Extended intermarker linkage disequilibrium in the Afrikaners.

PubMed

Hall, Diana; Wijsman, Ellen M; Roos, J Louw; Gogos, Joseph A; Karayiorgou, Maria

2002-06-01

In this study we conducted an investigation of the background level of linkage disequilibrium (LD) in the Afrikaner population to evaluate the appropriateness of this genetic isolate for mapping complex traits. We analyzed intermarker LD in 62 nuclear families using microsatellite markers covering extended chromosomal regions. The markers were selected to allow the first direct comparison of long-range LD in the Afrikaners to LD in other demographic groups. Using several statistical measures, we find significant evidence for LD in the Afrikaners extending remarkably over a 6-cM range. In contrast, LD decays significantly beyond 3-cM distances in the other founder and outbred populations examined. This study strongly supports the appropriateness of the Afrikaner population for genome-wide scans that exploit LD to map common, multigenic disorders.

Measuring treatment compliance of men with non-gonococcal urethritis receiving oxytetracycline combined with low dose phenobarbitone.

PubMed Central

Bignell, C J; Mulcahy, F M; Peaker, S; Pullar, T; Feely, M P

1988-01-01

Of 62 men with non-gonococcal urethritis who entered a study to assess compliance with treatment with oxytetracycline, only 33 could be evaluated. Traditional methods (interview and the absence of oxytetracycline in the urine) showed incomplete compliance in nine. Use of low dose phenobarbitone as a pharmacological marker showed incomplete compliance in a further five patients. In addition, phenobarbitone concentrations gave information on the extent to which individual patients had omitted treatment and provided direct, as opposed to circumstantial, evidence of good compliance by most (18) of those studied. Only three of the 33 patients whose compliance was assessed had evidence of continuing infection at follow up, and there was evidence of incomplete compliance in only one of these patients. PMID:3203931

Effect of chitosan conduit under a dynamic culture on the proliferation and neural differentiation of human exfoliated deciduous teeth stem cells.

PubMed

Su, Wen-Ta; Shih, Yi-An; Ko, Chih-Sheng

2016-06-01

Ex vivo engineering of artificial nerve conduit is a suitable alternative clinical treatment for nerve injuries. Stem cells from human exfoliated deciduous teeth (SHEDs) have been considered as alternative sources of adult stem cells because of their potential to differentiate into multiple cell lineages. These cells, when cultured in six-well plates, exhibited a spindle fibroblastic morphology, whereas those under a dynamic culture aggregated into neurosphere-like clusters in the chitosan conduit. In this study, we confirmed that SHEDs efficiently express the neural stem cell marker nestin, the early neural cell marker β-III-tubulin, the late neural marker neuron-specific enolase and the glial cell markers glial fibrillary acidic protein (GFAP) and 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase). The three-dimensional chitosan conduit and dynamic culture system generated fluid shear stress and enhanced nutrient transfer, promoting the differentiation of SHEDs to neural cells. In particular, the gene expressions of GFAP and CNPase increased by 28- and 53-fold, respectively. This study provides evidence for the dynamic culture of SHEDs during ex vivo neural differentiation and demonstrates its potential for cell therapy in neurological diseases. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

SE33 locus as a reliable genetic marker for forensic DNA analysis systems

PubMed

Bhinder, Munir Ahmad; Zahoor, Muhammad Yasir; Sadia, Haleema; Qasim, Muhammad; Perveen, Rukhsana; Anjum, Ghulam Murtaza; Iqbal, Muhammad; Ullah, Najeeb; Shehzad, Wasim; Tariq, Muhammad; Waryah, Ali Muhammad

2018-06-14

Background/aim: Genetic variation, an authentic tool of individual discrimination, is being used for forensic investigations worldwide. A missing result for even one out of 13-17 markers leads to an inconclusive report. Additional reliable markers are required to compensate such deficiencies. The SE33 locus has high genetic variability in different populations and is being used in forensic investigation systems in some countries. The purpose of the study was to assess the viability of use of the SE33 locus as a supportive marker for forensic DNA profiling. Materials and methods: Amplification of the SE33 locus was performed using the PowerPlex ES Monoplex System SE33 (Promega). After genotyping 204 Pakistani individuals, different genetic and forensic parameters for the SE33 locus were studied. Results: Genotyping of the SE33 locus revealed a total of 43 alleles including 3 novel alleles. Significant values of different forensic and genetic parameters including power of discrimination, power of exclusion, and polymorphism information content were observed. Conclusions: Addition of the SE33 locus in forensic DNA profiling may help to produce conclusive reports where results are inconclusive due to degraded evidence samples. The SE33 locus can confidently be used for Pakistani and neighboring populations having common ancestors from Iran to Central Asia, the Middle East, India and Turkey.

Control of origin of sesame oil from various countries by stable isotope analysis and DNA based markers--a pilot study.

PubMed

Horacek, Micha; Hansel-Hohl, Karin; Burg, Kornel; Soja, Gerhard; Okello-Anyanga, Walter; Fluch, Silvia

2015-01-01

The indication of origin of sesame seeds and sesame oil is one of the important factors influencing its price, as it is produced in many regions worldwide and certain provenances are especially sought after. We joined stable carbon and hydrogen isotope analysis with DNA based molecular marker analysis to study their combined potential for the discrimination of different origins of sesame seeds. For the stable carbon and hydrogen isotope data a positive correlation between both isotope parameters was observed, indicating a dominant combined influence of climate and water availability. This enabled discrimination between sesame samples from tropical and subtropical/moderate climatic provenances. Carbon isotope values also showed differences between oil from black and white sesame seeds from identical locations, indicating higher water use efficiency of plants producing black seeds. DNA based markers gave independent evidence for geographic variation as well as provided information on the genetic relatedness of the investigated samples. Depending on the differences in ambient environmental conditions and in the genotypic fingerprint, a combination of both analytical methods is a very powerful tool to assess the declared geographic origin. To our knowledge this is the first paper on food authenticity combining the stable isotope analysis of bio-elements with DNA based markers and their combined statistical analysis.

Population structure and genotypic variation of Crataegus pontica inferred by molecular markers.

PubMed

Rahmani, Mohammad-Shafie; Shabanian, Naghi; Khadivi-Khub, Abdollah; Woeste, Keith E; Badakhshan, Hedieh; Alikhani, Leila

2015-11-01

Information about the natural patterns of genetic variability and their evolutionary bases are of fundamental practical importance for sustainable forest management and conservation. In the present study, the genetic diversity of 164 individuals from fourteen natural populations of Crataegus pontica K.Koch was assessed for the first time using three genome-based molecular techniques; inter-retrotransposon amplified polymorphism (IRAP); inter-simple sequence repeats (ISSR) and start codon targeted (SCoT) polymorphism. IRAP, ISSR and SCoT analyses yielded 126, 254 and 199 scorable amplified bands, respectively, of which 90.48, 93.37 and 83.78% were polymorphic. ISSR revealed efficiency over IRAP and SCoT due to high effective multiplex ratio, marker index and resolving power. The dendrograms based on the markers used and combined data divided individuals into three major clusters. The correlation between the coefficient matrices for the IRAP, ISSR and SCoT data was significant. A higher level of genetic variation was observed within populations than among populations based on the markers used. The lower divergence levels depicted among the studied populations could be seen as evidence of gene flow. The promotion of gene exchange will be very beneficial to conserve and utilize the enormous genetic variability. Copyright © 2015 Elsevier B.V. All rights reserved.

Management options for echogenic intracardiac focus and choroid plexus cysts: a review including Australian Association of Obstetrical and Gynaecological Ultrasonologists consensus statement.

PubMed

Bethune, M

2007-08-01

Echogenic intracardiac focus and choroid plexus cysts are common findings at the midtrimester ultrasound. These findings have been linked with an increased risk of Down syndrome and trisomy 18. Most fetuses with these findings will, however, not have chromosomal abnormalities, especially when these findings are isolated. Patients experience considerable anxiety when informed of these findings and require extensive counselling in order to minimize anxiety not only about aneuploidy but also about the structure and development of the heart and brain. Although early studies showed an association with aneuploidies, several recent studies have cast doubt on this association. Many of the early studies were carried out in high-risk populations or in populations that had not had the benefit of other screening tests. Many Australian and New Zealand patients will access screening tests designed to detect these aneuploidies before presenting for a midtrimester ultrasound. Patients who have been screened by nuchal translucency, maternal serum screening or some combination of the two will already have had most cases of Down syndrome and trisomy 18 detected, and any soft marker found will almost certainly be a false positive. It is time to rethink the management of these markers. Recent evidence indicates that if these markers are found in isolation in an otherwise low-risk pregnancy, then there is minimal or no increase in the risk of Down syndrome or trisomy 18: these markers should be considered normal variants. The Australian Association of Obstetrical and Gynaecological Ultrasonologists consensus statement on these markers is included.

Optimizing trial design in pharmacogenetics research: comparing a fixed parallel group, group sequential, and adaptive selection design on sample size requirements.

PubMed

Boessen, Ruud; van der Baan, Frederieke; Groenwold, Rolf; Egberts, Antoine; Klungel, Olaf; Grobbee, Diederick; Knol, Mirjam; Roes, Kit

2013-01-01

Two-stage clinical trial designs may be efficient in pharmacogenetics research when there is some but inconclusive evidence of effect modification by a genomic marker. Two-stage designs allow to stop early for efficacy or futility and can offer the additional opportunity to enrich the study population to a specific patient subgroup after an interim analysis. This study compared sample size requirements for fixed parallel group, group sequential, and adaptive selection designs with equal overall power and control of the family-wise type I error rate. The designs were evaluated across scenarios that defined the effect sizes in the marker positive and marker negative subgroups and the prevalence of marker positive patients in the overall study population. Effect sizes were chosen to reflect realistic planning scenarios, where at least some effect is present in the marker negative subgroup. In addition, scenarios were considered in which the assumed 'true' subgroup effects (i.e., the postulated effects) differed from those hypothesized at the planning stage. As expected, both two-stage designs generally required fewer patients than a fixed parallel group design, and the advantage increased as the difference between subgroups increased. The adaptive selection design added little further reduction in sample size, as compared with the group sequential design, when the postulated effect sizes were equal to those hypothesized at the planning stage. However, when the postulated effects deviated strongly in favor of enrichment, the comparative advantage of the adaptive selection design increased, which precisely reflects the adaptive nature of the design. Copyright © 2013 John Wiley & Sons, Ltd.

A study of chromosome 4p markers and dopamine D5 receptor gene in schizophrenia and bipolar disorder.

PubMed

Asherson, P; Mant, R; Williams, N; Cardno, A; Jones, L; Murphy, K; Collier, D A; Nanko, S; Craddock, N; Morris, S; Muir, W; Blackwood, B; McGuffin, P; Owen, M J

1998-07-01

There are several lines of evidence which suggest that chromosome 4p may contain a major susceptibility locus for the functional psychoses. We previously reported a family (family 50) with cases of schizophrenia and schizoaffective disorder which gave maximum lod scores of 1.96 and 1.84 respectively with the markers D4S403 and a microsatellite near to DRD5 (DRD5-M). More recently Blackwood and co-workers described a family segregating bipolar and unipolar affective disorders which gives a maximum lod score of 4.1 with the marker D4S394, which lies 10 cM from D4S403. They obtained a combined maximum lod of 3.3 in their total sample of 12 bipolar families and found significant evidence of heterogeneity (chi 2 = 18.8, df = 2, P = 0.00008). Here we report the results of a linkage study of chromosome 4p markers in a sample of 24 multiply affected families with schizophrenia and related disorders. We obtained an overall maximum lod of 1.12 with D4S403 under both dominant and recessive modes of transmission, with no statistical support for heterogeneity within our sample. Examination of family by family data shows that only family 50 appears to show linkage at this locus. However, a discrepancy exists since our study examined families fulfilling criteria for a linkage study of schizophrenia while Blackwood et al examined families included in a genetic linkage study of bipolar disorder. This may be explained by the clinical features displayed by members of family 50, which show that all the affected members have some affective symptoms. It is therefore possible that a broad phenotype including unipolar depression, bipolar disorder, schizoaffective disorder and schizophrenia when accompanied by significant affective symptoms can result from mutations within a gene in this region. The dopamine D5 receptor gene lies within the region identified by the linkage studies and is therefore a major candidate for the putative disease gene. In family 50 we have looked for mutations of DRD5 by sequence analysis of the coding region and single stranded conformational polymorphism (SSCP) analysis of the promoter. SSCP analysis of the coding and promoter regions have also been carried out in unrelated cases of DSM-IIIR schizophrenia. Finally association studies of the (TC)n repeat in the promoter and schizophrenia, and DRD5-M and bipolar disorder were performed. These studies provided no further evidence supporting the possibility that mutations in DRD5 give rise to the linkage findings or are acting as susceptibility loci in schizophrenia or bipolar disorder.

Endocrinology and Adolescence: aerobic exercise reduces insulin resistance markers in obese youth: a meta-analysis of randomized controlled trials.

PubMed

García-Hermoso, Antonio; Saavedra, Jose M; Escalante, Yolanda; Sánchez-López, Mairena; Martínez-Vizcaíno, Vicente

2014-10-01

The purpose of this meta-analysis was to examine the evidence for the effectiveness of aerobic exercise interventions on reducing insulin resistance markers in obese children and/or adolescents. A secondary outcome was change in percentage of body fat. A computerized search was made from seven databases: CINAHL, Cochrane Central Register of Controlled Trials, EMBASE, ERIC, MEDLINE, PsycINFO, and Science Citation Index. The analysis was restricted to randomized controlled trials that examined the effect of aerobic exercise on insulin resistance markers in obese youth. Two independent reviewers screened studies and extracted data. Effect sizes (ES) and 95% confidence interval (CI) were calculated, and the heterogeneity of the studies was estimated using Cochran's Q-statistic. Nine studies were selected for meta-analysis as they fulfilled the inclusion criteria (n=367). Aerobic exercise interventions resulted in decreases in fasting glucose (ES=-0.39; low heterogeneity) and insulin (ES=-0.40; low heterogeneity) and in percentage of body fat (ES=-0.35; low heterogeneity). These improvements were specifically accentuated in adolescents (only in fasting insulin), or through programs lasting more than 12 weeks, three sessions per week, and over 60 min of aerobic exercise per session. This meta-analysis provides insights into the effectiveness of aerobic exercise interventions on insulin resistance markers in the obese youth population. © 2014 European Society of Endocrinology.

Identification of fecal contamination sources in water using host-associated markers.

PubMed

Krentz, Corinne A; Prystajecky, Natalie; Isaac-Renton, Judith

2013-03-01

In British Columbia, Canada, drinking water is tested for total coliforms and Escherichia coli, but there is currently no routine follow-up testing to investigate fecal contamination sources in samples that test positive for indicator bacteria. Reliable microbial source tracking (MST) tools to rapidly test water samples for multiple fecal contamination markers simultaneously are currently lacking. The objectives of this study were (i) to develop a qualitative MST tool to identify fecal contamination from different host groups, and (ii) to evaluate the MST tool using water samples with evidence of fecal contamination. Singleplex and multiplex polymerase chain reaction (PCR) were used to test (i) water from polluted sites and (ii) raw and drinking water samples for presence of bacterial genetic markers associated with feces from humans, cattle, seagulls, pigs, chickens, and geese. The multiplex MST assay correctly identified suspected contamination sources in contaminated waterways, demonstrating that this test may have utility for heavily contaminated sites. Most raw and drinking water samples analyzed using singleplex PCR contained at least one host-associated marker. Singleplex PCR was capable of detecting host-associated markers in small sample volumes and is therefore a promising tool to further analyze water samples submitted for routine testing and provide information useful for water quality management.

Source-specific fine particulate air pollution and systemic inflammation in ischaemic heart disease patients

PubMed Central

Siponen, Taina; Yli-Tuomi, Tarja; Aurela, Minna; Dufva, Hilkka; Hillamo, Risto; Hirvonen, Maija-Riitta; Huttunen, Kati; Pekkanen, Juha; Pennanen, Arto; Salonen, Iiris; Tiittanen, Pekka; Salonen, Raimo O; Lanki, Timo

2015-01-01

Objective To compare short-term effects of fine particles (PM2.5; aerodynamic diameter <2.5 µm) from different sources on the blood levels of markers of systemic inflammation. Methods We followed a panel of 52 ischaemic heart disease patients from 15 November 2005 to 21 April 2006 with clinic visits in every second week in the city of Kotka, Finland, and determined nine inflammatory markers from blood samples. In addition, we monitored outdoor air pollution at a fixed site during the study period and conducted a source apportionment of PM2.5 using the Environmental Protection Agency's model EPA PMF 3.0. We then analysed associations between levels of source-specific PM2.5 and markers of systemic inflammation using linear mixed models. Results We identified five source categories: regional and long-range transport (LRT), traffic, biomass combustion, sea salt, and pulp industry. We found most evidence for the relation of air pollution and inflammation in LRT, traffic and biomass combustion; the most relevant inflammation markers were C-reactive protein, interleukin-12 and myeloperoxidase. Sea salt was not positively associated with any of the inflammatory markers. Conclusions Results suggest that PM2.5 from several sources, such as biomass combustion and traffic, are promoters of systemic inflammation, a risk factor for cardiovascular diseases. PMID:25479755

Value of DNA tests: a decision perspective.

PubMed

Taroni, Franco; Bozza, Silvia; Bernard, Magali; Champod, Christophe

2007-01-01

Before a Court of Law testifying in DNA-evidence cases, scientists are often challenged with the idea that the more markers (loci) the better, i.e., why does the scientist not use 16 or more markers? This paper introduces a new perspective, decision analysis, to deal with the problem of the number of markers to type in a criminal context. The decision-making process, which plays a key role in the routine work of a forensic scientist, consists of the rational choice, given personal objectives, between two or more possible outcomes when the consequences of the choice are uncertain. Simulated results support the hypothesis that analytical added value does not increase with the number of markers.

High intensity interval running enhances measures of physical fitness but not metabolic measures of cardiovascular disease risk in healthy adolescents

PubMed Central

2013-01-01

Background With accumulating evidence suggesting that CVD has its origins in childhood, the purpose of this study was to examine whether a high intensity training (HIT) intervention could enhance the CVD risk profile of secondary school aged adolescents in a time efficient manner. Methods Participants in the study were adolescent school children (64 boys, 25 girls, 16.7 ± 0.6 years). The intervention group (30 boys, 12 girls) performed three weekly exercise sessions over 7 weeks with each session consisting of either four to six repeats of maximal sprint running within a 20 m area with 30 s recovery. The control group were instructed to continue their normal behaviour. All participants had indices of obesity, blood pressure and nine biochemical risk markers for cardiovascular disease recorded as well as four physical performance measures at baseline and post-intervention. Feedback was provided through informal discussion throughout the intervention period as well as post-intervention focus groups. Statistical differences between and within groups were determined by use of paired samples t-tests and ANCOVA. Results Significant enhancements (P ≤ 0.05) in vertical jump performance, 10 m sprint speed and cardiorespiratory fitness was evident in the intervention group whereas a significant decrease in both agility and vertical jump performance was evident in the control group. Participants in the intervention group also experienced a significant decrease in systolic blood pressure post-intervention. Limited changes occurred with respect to the biochemical markers although both groups did experience a significant increase in LDL post-intervention whilst the control group experienced a significant decrease in total cholesterol. No apparent differences were evident between groups post intervention for any of the biochemical markers. Feedback indicated that participants endorsed the use of the intervention as an effective means of exercise. Conclusions Our results demonstrate that high intensity exercise interventions may be used in the school setting for adolescents as a means of improving measures of physical fitness. Further investigations involving a larger cohort of participants, taken from different schools, is recommended. Trial registration NCT01027156 PMID:23705968

Evaluating the Intervention-Based Evidence Surrounding the Causal Role of Breakfast on Markers of Weight Management, with Specific Focus on Breakfast Composition and Size1234

PubMed Central

Leidy, Heather J; Gwin, Jess A; Roenfeldt, Connor A; Zino, Adam Z; Shafer, Rebecca S

2016-01-01

Nutritional strategies are vitally needed to aid in the management of obesity. Cross-sectional and epidemiologic studies consistently demonstrate that breakfast consumption is strongly associated with a healthy body weight. However, the intervention-based long-term evidence supporting a causal role of breakfast consumption is quite limited and appears to be influenced by several key dietary factors, such as dietary protein, fiber, and energy content. This article provides a comprehensive review of the intervention-based literature that examines the effects of breakfast consumption on markers of weight management and daily food intake. In addition, specific focus on the composition and size (i.e., energy content) of the breakfast meal is included. Overall, there is limited evidence supporting (or refuting) the daily consumption of breakfast for body weight management and daily food intake. In terms of whether the type of breakfast influences these outcomes, there is accumulating evidence supporting the consumption of increased dietary protein and fiber content at breakfast, as well as the consumption of more energy during the morning hours. However, the majority of the studies that manipulated breakfast composition and content did not control for habitual breakfast behaviors, nor did these studies include a breakfast-skipping control arm. Thus, it is unclear whether the addition of these types of breakfast plays a causal role in weight management. Future research, including large randomized controlled trials of longer-term (i.e., ≥6 mo) duration with a focus on key dietary factors, is critical to begin to assess whether breakfast recommendations are appropriate for the prevention and/or treatment of obesity. PMID:27184285

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

Salt and hypertension: what do we know?

PubMed

DiNicolantonio, James J; O'Keefe, James H

2018-07-01

To evaluate the evidence for population-wide sodium restriction. The recommendations for population-wide sodium restriction largely rely on one surrogate marker (blood pressure). However, recent evidence suggests that when looking beyond blood pressure (e.g. heart rate, aldosterone, renin, cholesterol, triglycerides, noradrenaline and adrenaline), the net effect of sodium restriction is likely harmful. Prospective studies support the notion that those consuming the lowest amounts of salt are at the highest risk of cardiovascular events and premature death. There is no definitive proof that sodium restriction reduces cardiovascular events or death. It is time for the dietary guidelines to look at the totality of the evidence and reconsider the advice around population-wide sodium restriction.

Profiling of normal and malignant breast tissue show CD44high/CD24low phenotype as a predominant stem/progenitor marker when used in combination with Ep-CAM/CD49f markers

PubMed Central

2013-01-01

Background Accumulating evidence supports cancer to initiate and develop from a small population of stem-like cells termed as cancer stem cells (CSC). The exact phenotype of CSC and their counterparts in normal mammary gland is not well characterized. In this study our aim was to evaluate the phenotype and function of stem/progenitor cells in normal mammary epithelial cell populations and their malignant counterparts. Methods Freshly isolated cells from both normal and malignant human breasts were sorted using 13 widely used stem/progenitor cell markers individually or in combination by multi-parametric (up to 9 colors) cell sorting. The sorted populations were functionally evaluated by their ability to form colonies and mammospheres, in vitro. Results We have compared, for the first time, the stem/progenitor markers of normal and malignant breasts side-by-side. Amongst all markers tested, we found CD44high/CD24low cell surface marker combination to be the most efficient at selecting normal epithelial progenitors. Further fractionation of CD44high/CD24low positive cells showed that this phenotype selects for luminal progenitors within Ep-CAMhigh/CD49f + cells, and enriches for basal progenitors within Ep-CAM-/low/CD49f + cells. On the other hand, primary breast cancer samples, which were mainly luminal Ep-CAMhigh, had CD44high/CD24low cells among both CD49fneg and CD49f + cancer cell fractions. However, functionally, CSC were predominantly CD49f + proposing the use of CD44high/CD24low in combination with Ep-CAM/CD49f cell surface markers to further enrich for CSC. Conclusion Our study clearly demonstrates that both normal and malignant breast cells with the CD44high/CD24low phenotype have the highest stem/progenitor cell ability when used in combination with Ep-CAM/CD49f reference markers. We believe that this extensive characterization study will help in understanding breast cancer carcinogenesis, heterogeneity and drug resistance. PMID:23768049

Expectations Do Not Alter Early Sensory Processing during Perceptual Decision-Making.

PubMed

Rungratsameetaweemana, Nuttida; Itthipuripat, Sirawaj; Salazar, Annalisa; Serences, John T

2018-06-13

Two factors play important roles in shaping perception: the allocation of selective attention to behaviorally relevant sensory features, and prior expectations about regularities in the environment. Signal detection theory proposes distinct roles of attention and expectation on decision-making such that attention modulates early sensory processing, whereas expectation influences the selection and execution of motor responses. Challenging this classic framework, recent studies suggest that expectations about sensory regularities enhance the encoding and accumulation of sensory evidence during decision-making. However, it is possible, that these findings reflect well documented attentional modulations in visual cortex. Here, we tested this framework in a group of male and female human participants by examining how expectations about stimulus features (orientation and color) and expectations about motor responses impacted electroencephalography (EEG) markers of early sensory processing and the accumulation of sensory evidence during decision-making (the early visual negative potential and the centro-parietal positive potential, respectively). We first demonstrate that these markers are sensitive to changes in the amount of sensory evidence in the display. Then we show, counter to recent findings, that neither marker is modulated by either feature or motor expectations, despite a robust effect of expectations on behavior. Instead, violating expectations about likely sensory features and motor responses impacts posterior alpha and frontal theta oscillations, signals thought to index overall processing time and cognitive conflict. These findings are inconsistent with recent theoretical accounts and suggest instead that expectations primarily influence decisions by modulating post-perceptual stages of information processing. SIGNIFICANCE STATEMENT Expectations about likely features or motor responses play an important role in shaping behavior. Classic theoretical frameworks posit that expectations modulate decision-making by biasing late stages of decision-making including the selection and execution of motor responses. In contrast, recent accounts suggest that expectations also modulate decisions by improving the quality of early sensory processing. However, these effects could instead reflect the influence of selective attention. Here we examine the effect of expectations about sensory features and motor responses on a set of electroencephalography (EEG) markers that index early sensory processing and later post-perceptual processing. Counter to recent empirical results, expectations have little effect on early sensory processing but instead modulate EEG markers of time-on-task and cognitive conflict. Copyright © 2018 the authors 0270-6474/18/385632-17$15.00/0.

Normalization of Elevated Tumor Marker CA27-29 after Bilateral Lung Transplantation in a patient with Breast Cancer and Idiopathic Pulmonary Fibrosis.

PubMed

Copur, Mehmet Sitki; Wurdeman, Julie Marie; Nelson, Debra; Ramaekers, Ryan; Gauchan, Dron; Crockett, David

2017-12-11

Solid tumors involving glandular organs express mucin glycoprotein which is eventually shed into the circulation. As aresult these proteins can easily be measured in the serum and be used as potential tumor markers. The most commonly used tumor markers for breast cancer are CA 27-29 and CA 15-3, which both measure the glycoprotein product of the mucin-1 (MUC1) gene. CA 27-29 has been approved by the US Food and Drug Administration for monitoring disease activity in breast cancer patients. Most oncology clinical practice guidelines do not recommend the use of tumor markers for routine surveillance of early stage disease but recognize their utility in the metastatic setting. Herein, we present a patient with stage III-A breast cancer and pre-existing hypersensitivity pneumonitis who is found to have an elevated serum tumor marker CA 27-29. After successful curative intent treatment of her early stage breast cancer, she developed gradual and progressive worsening of her lung disease with eventual development of severe pulmonary fibrosis requiring bilateral lung transplantation. As part of the pre-transplant evaluation, she was found to have an elevation of serum tumor marker CA 27-29. While the diagnostic evaluation, including imaging studies was negative for the presence of recurrent disease, the serial serum tumor marker CA 27-29 levels remained persistently elevated. The decision was made for her to undergo bilateral lung transplantation. Shortly after surgery her CA27-29 tumor marker level returned to normal range, and it has continued to remain in the normal range with no evidence of breast cancer recurrence.

Biochemical marker reference values across pediatric, adult, and geriatric ages: establishment of robust pediatric and adult reference intervals on the basis of the Canadian Health Measures Survey.

PubMed

Adeli, Khosrow; Higgins, Victoria; Nieuwesteeg, Michelle; Raizman, Joshua E; Chen, Yunqi; Wong, Suzy L; Blais, David

2015-08-01

Biological covariates such as age and sex can markedly influence biochemical marker reference values, but no comprehensive study has examined such changes across pediatric, adult, and geriatric ages. The Canadian Health Measures Survey (CHMS) collected comprehensive nationwide health information and blood samples from children and adults in the household population and, in collaboration with the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER), examined biological changes in biochemical markers from pediatric to geriatric age, establishing a comprehensive reference interval database for routine disease biomarkers. The CHMS collected health information, physical measurements, and biosamples (blood and urine) from approximately 12 000 Canadians aged 3-79 years and measured 24 biochemical markers with the Ortho Vitros 5600 FS analyzer or a manual microplate. By use of CLSI C28-A3 guidelines, we determined age- and sex-specific reference intervals, including corresponding 90% CIs, on the basis of specific exclusion criteria. Biochemical marker reference values exhibited dynamic changes from pediatric to geriatric age. Most biochemical markers required some combination of age and/or sex partitioning. Two or more age partitions were required for all analytes except bicarbonate, which remained constant throughout life. Additional sex partitioning was required for most biomarkers, except bicarbonate, total cholesterol, total protein, urine iodine, and potassium. Understanding the fluctuations in biochemical markers over a wide age range provides important insight into biological processes and facilitates clinical application of biochemical markers to monitor manifestation of various disease states. The CHMS-CALIPER collaboration addresses this important evidence gap and allows the establishment of robust pediatric and adult reference intervals. © 2015 American Association for Clinical Chemistry.

The relationship between genetic and chemotypic diversity in American ginseng (Panax quinquefolius L.).

PubMed

Schlag, Erin M; McIntosh, Marla S

2013-09-01

Ginseng is one of the world's most important herbals used as an adaptogen and a cure for an impressively large range of ailments. Differences in the medicinal properties of ginseng roots have been attributed to variation in ginsenoside composition. In this study, the association between genetic and chemotypic profiles of wild and cultivated American ginseng (Panax quinquefolius L.) roots grown in Maryland was investigated. Ginseng roots were classified into chemotypes based on their relative composition of Re and Rg1. Genetic profiles of these roots were determined from the analysis of 38 polymorphic RAPD markers and used for a cluster analysis of genetic similarities. The close correspondence between chemotype and genetic cluster provides the first DNA-based evidence for the genetic basis of ginsenoside composition. Results of this research are significant for plant breeding and conservation, phytochemical research, and clinical and pharmacological studies. Also, the correlation between RAPD markers and chemotype indicates the potential to use RAPD markers as a reliable and practical method for identification and certification of ginseng roots. Copyright © 2013 Elsevier Ltd. All rights reserved.

Potential linkage for schizophrenia on chromosome 22q12-q13: A replication study

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

Schwab, S.G.; Bondy, B.; Wildenauer, D.B.

1995-10-09

In an attempt to replicate a potential linkage on chromosome 22q12-q13.1 reported by Pulver et al., we have analyzed 4 microsatellite markers which span this chromosomal region, including the IL2RB locus, for linkage with schizophrenia in 30 families from Israel and Germany. Linkage analysis by pairwise lod score analysis as well as by multipoint analysis did not provide evidence for a single major gene locus. However, a lod score of Z{sub max} = 0.612 was obtained for a dominant model of inheritance with the marker D22S304 at recombination fraction 0.2 by pairwise analysis. In addition, using a nonparametric method, sibmore » pair analysis, a P value of 0.068 corresponding to a lod score of 0.48 was obtained for this marker. This finding, together with those of Pulver et al., is suggestive of a genetic factor in this region, predisposing for schizophrenia in a subset of families. Further studies using nonparametric methods should be conducted in order to clarify this point. 32 refs., 1 fig., 4 tabs.« less

Immunohistochemical expression of vegf and her-2 proteins in osteosarcoma biopsies

PubMed Central

Becker, Ricardo Gehrke; Galia, Carlos Roberto; Morini, Sandra; Viana, Cristiano Ribeiro

2013-01-01

OBJECTIVES: To identify the prevalence of erbB-2 and vascular endothelial growth factor (VEGF) in osteosarcoma biopsies and to correlate them with possible prognosis factors. METHODS: Retrospective study conducted at the Hospital do Câncer de Barretos-SP including 27 osteosarcoma biopsies immunohistochemically stained for VEGF and erbB-2. The pathological characteristics were collected from medical records of patients to correlate with markers. RESULTS: In 27 biopsies, four overexpressed VEGF and three overexpressed erbB-2. Two thirds of patients had no metastases. Almost all patients with overexpression of VEGF showed metastases. Overexpression of erbB-2 was inversely related to the presence of metastases. There was no significant association between markers and prognosis. CONCLUSION: We identified a low prevalence of erbB-2 and VEGF in the sample. There was no significant association between overexpression of markers and pathological features. A larger sample and a longer follow-up, in addition to using new laboratory techniques can determine the real expression of VEGF and erbB-2 and its role in osteosarcoma. Level of Evidence III, Case-Control Study. PMID:24453675

Baseline and storm event monitoring of Bacteroidales marker concentrations and enteric pathogen presence in a rural Canadian watershed.

PubMed

Ridley, C M; Jamieson, R C; Truelstrup Hansen, L; Yost, C K; Bezanson, G S

2014-09-01

Bacteroidales 16S rRNA gene markers were evaluated for their use as a microbial source tracking tool in a well characterized 750 ha agricultural watershed in Nova Scotia, Canada. Water quality monitoring was conducted following the validation of host-specific and universal Bacteroidales (AllBac) markers for their proficiency in this particular geographic region, which provided further evidence that these markers are geographically stable. Increasing Escherichia coli concentrations were positively correlated (p < 0.01) with concentrations of the AllBac marker in water samples, suggesting that this universal marker is more suited as a positive DNA control rather than as an indicator of recent fecal contamination. Ruminant (BacR) and bovine (CowM2) specific marker detection was associated with increased runoff due to precipitation in sub-watersheds putatively impacted by cattle farming, demonstrating that the BacR and CowM2 markers can be used to detect the recent introduction of fecal matter from cattle farming activities during rainfall events. However, the human associated marker (BacH) was only detected once in spite of numerous on-site residential wastewater treatment systems in the watershed, suggesting that this assay is not sensitive enough to detect this type of human sewage source. E. coli O157:H7 and Salmonella spp. DNA was not detected in any of the 149 watershed samples; however, 114 (76.5%) of those samples tested positive for Campylobacter spp. No significant correlation (p > 0.05) was found between Campylobacter spp. presence and either E. coli or AllBac marker levels. Further studies should be conducted to assess the origins of Campylobacter spp. in these types of watersheds, and to quantify pathogen cell numbers to allow for a human health risk assessment. Copyright © 2014 Elsevier Ltd. All rights reserved.

A combined analysis of D22S278 marker alleles in affected sib-pairs: Support for a susceptibility locus for schizophrenia at chromosome 22q12

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

Gill, M.; Vallada, H.; Collier, D.

1996-02-16

Several groups have reported weak evidence for linkage between schizophrenia and genetic markers located on chromosome 22q using the lod score method of analysis. However these findings involved different genetic markers and methods of analysis, and so were not directly comparable. To resolve this issue we have performed a combined analysis of genotypic data from the marker D22S278 in multiply affected schizophrenic families derived from 11 independent research groups worldwide. This marker was chosen because it showed maximum evidence for linkage in three independent datasets. Using the affected sib-pair method as implemented by the program ESPA, the combined dataset showedmore » 252 alleles shared compared with 188 alleles not shared (chi-square 9.31, 1df, P = 0.001) where parental genotype data was completely known. When sib-pairs for whom parental data was assigned according to probability were included the number of alleles shared was 514.1 compared with 437.8 not shared (chi-square 6.12, 1df, P = 0.006). Similar results were obtained when a likelihood ratio method for sib-pair analysis was used. These results indicate that there may be a susceptibility locus for schizophrenia at 22q12. 27 refs., 3 tabs.« less

Physical Exercise on Inflammatory Markers in Type 2 Diabetes Patients: A Systematic Review of Randomized Controlled Trials

PubMed Central

Melo, Luciana Costa; Dativo-Medeiros, Jaime; Menezes-Silva, Carlos Eduardo; de Sousa-Rodrigues, Célio Fernando

2017-01-01

Background. Type 2 diabetes mellitus (T2DM) is a serious disease associated with high morbidity and mortality. Scientific findings showed that physical exercise is an option for treatment of these patients. This study's objective is to investigate the effects of supervised aerobic and/or resistance physical training on inflammatory markers in subjects with T2DM. Methods. A systematic review was conducted on four databases, MEDLINE, CENTRAL, LILACS, and Scopus, and manual search from 21 to 30 November 2016. Randomized clinical trials involving individuals diagnosed with T2DM, who have undergone supervised training protocols, were selected in this study. Results. Eleven studies were included. Studies that evaluated control group versus aerobic exercise reported controversial results about the effectiveness of physical training in modifying C-reactive protein (CRP) and cytokine levels. The only variable analyzed by the six studies in comparison to the control group versus resistance exercise was CRP. This protein showed no significant difference between groups. Between the two modes of exercise (aerobic and resistance), only one study demonstrated that aerobic exercise was more effective in reducing CRP. Conclusion. The evidence was insufficient to prove that aerobic or resistance exercise improves systemic levels of inflammatory markers in patients with T2DM. PMID:28400914

The Interrelations of Features of Questions, Mark Schemes and Examinee Responses and Their Impact upon Marker Agreement

ERIC Educational Resources Information Center

Black, Beth; Suto, Irenka; Bramley, Tom

2011-01-01

In this paper we develop an evidence-based framework for considering many of the factors affecting marker agreement in GCSEs and A levels. A logical analysis of the demands of the marking task suggests a core grouping comprising: (i) question features; (ii) mark scheme features; and (iii) examinee response features. The framework synthesises…

Relationship between inflammation, insulin resistance and type 2 diabetes: 'cause or effect'?

PubMed

Greenfield, Jerry R; Campbell, Lesley V

2006-05-01

Inflammation has been implicated as an important aetiological factor in the development of both insulin resistance and type 2 diabetes mellitus. This conclusion is predominantly drawn from studies demonstrating associations between elevated (but 'normal range') levels of circulating acute phase inflammatory markers, typified by C-reactive protein (CRP), and indices of insulin resistance and the development of type 2 diabetes. There is debate as to whether these associations are independent of body fatness or, rather, an epiphenomenon of obesity, particularly central obesity, a strong predictor of insulin resistance and type 2 diabetes and an important source of inflammatory cytokines, such as interleukin-6. Some of this controversy and the inability to draw definitive conclusions from these studies relate to the fact that most studies measure body fat and its distribution indirectly using anthropometric estimates, such as Body Mass Index and waist circumference, rather than directly by dual-energy X-ray absorptiometry, computed tomography or magnetic resonance imaging. Furthermore, use of the term inflammation may be inappropriate when describing mild elevations of CRP in the 'normal range' in the absence of the other changes that characterise classical inflammatory diseases, such as a reduction in levels (or evidence of consumption) of complement proteins. Debate as to whether obesity mediates the association between circulating levels of inflammatory markers and insulin resistance can be resolved by well-designed studies using body fat measured by gold-standard methods. In this review, we present evidence to support the suggestion that body fat is the primary determinant of circulating inflammatory marker levels in the basal state and that marginally elevated levels of circulating interleukin-6 and CRP in obesity are a consequence rather than a cause of insulin resistance. The importance of genetic influences in determining both body fatness and circulating CRP levels will also be discussed. The review will conclude with a discussion of possible mechanisms linking body fat and insulin resistance to elevated circulating levels of inflammatory markers, including the possible role of the toll-like family of immune receptors.

Impact of Cocoa Consumption on Inflammation Processes—A Critical Review of Randomized Controlled Trials

PubMed Central

Ellinger, Sabine; Stehle, Peter

2016-01-01

Background: Cocoa flavanols have strong anti-inflammatory properties in vitro. If these also occur in vivo, cocoa consumption may contribute to the prevention or treatment of diseases mediated by chronic inflammation. This critical review judged the evidence for such effects occurring after cocoa consumption. Methods: A literature search in Medline was performed for randomized controlled trials (RCTs) that investigated the effects of cocoa consumption on inflammatory biomarkers. Results: Thirty-three RCTs were included, along with 9 bolus and 24 regular consumption studies. Acute cocoa consumption decreased adhesion molecules and 4-series leukotrienes in serum, nuclear factor κB activation in leukocytes, and the expression of CD62P and CD11b on monocytes and neutrophils. In healthy subjects and in patients with cardiovascular diseases, most regular consumption trials did not find any changes except for a decreased number of endothelial microparticles, but several cellular and humoral inflammation markers decreased in patients suffering from type 2 diabetes and impaired fasting glucose. Conclusions: Little evidence exists that consumption of cocoa-rich food may reduce inflammation, probably by lowering the activation of monocytes and neutrophils. The efficacy seems to depend on the extent of the basal inflammatory burden. Further well-designed RCTs with inflammation as the primary outcome are needed, focusing on specific markers of leukocyte activation and considering endothelial microparticles as marker of vascular inflammation. PMID:27240397

Cancer stem cells in colorectal cancer: a review.

PubMed

Munro, Matthew J; Wickremesekera, Susrutha K; Peng, Lifeng; Tan, Swee T; Itinteang, Tinte

2018-02-01

Colorectal cancer (CRC) is the second most common cancer in women and the third most common in men. Adenocarcinoma accounts for 90% of CRC cases. There has been accumulating evidence in support of the cancer stem cell (CSC) concept of cancer which proposes that CSCs are central in the initiation of cancer. CSCs have been the focus of study in a range of cancers, including CRC. This has led to the identification and understanding of genes involved in the induction and maintenance of pluripotency of stem cells, and markers for CSCs, including those investigated specifically in CRC. Knowledge of the expression pattern of CSCs in CRC has been increasing in recent years, revealing a heterogeneous population of cells within CRC ranging from pluripotent to differentiated cells, with overlapping and sometimes unique combinations of markers. This review summarises current literature on the understanding of CSCs in CRC, including evidence of the presence of CSC subpopulations, and the stem cell markers currently used to identify and localise these CSC subpopulations. Future research into this field may lead to improved methods for early detection of CRC, novel therapy and monitoring of treatment for CRC and other cancer types. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Impact of Cocoa Consumption on Inflammation Processes-A Critical Review of Randomized Controlled Trials.

PubMed

Ellinger, Sabine; Stehle, Peter

2016-05-26

Cocoa flavanols have strong anti-inflammatory properties in vitro. If these also occur in vivo, cocoa consumption may contribute to the prevention or treatment of diseases mediated by chronic inflammation. This critical review judged the evidence for such effects occurring after cocoa consumption. A literature search in Medline was performed for randomized controlled trials (RCTs) that investigated the effects of cocoa consumption on inflammatory biomarkers. Thirty-three RCTs were included, along with 9 bolus and 24 regular consumption studies. Acute cocoa consumption decreased adhesion molecules and 4-series leukotrienes in serum, nuclear factor κB activation in leukocytes, and the expression of CD62P and CD11b on monocytes and neutrophils. In healthy subjects and in patients with cardiovascular diseases, most regular consumption trials did not find any changes except for a decreased number of endothelial microparticles, but several cellular and humoral inflammation markers decreased in patients suffering from type 2 diabetes and impaired fasting glucose. Little evidence exists that consumption of cocoa-rich food may reduce inflammation, probably by lowering the activation of monocytes and neutrophils. The efficacy seems to depend on the extent of the basal inflammatory burden. Further well-designed RCTs with inflammation as the primary outcome are needed, focusing on specific markers of leukocyte activation and considering endothelial microparticles as marker of vascular inflammation.

Is Post-Traumatic Stress Disorder Associated with Premature Senescence? A Review of the Literature

PubMed Central

Lohr, James B.; Palmer, Barton W.; Eidt, Carolyn A.; Aailaboyina, Smitha; Mausbach, Brent T.; Wolkowitz, Owen M.; Thorp, Steven R.; Jeste, Dilip V.

2015-01-01

Post-Traumatic Stress Disorder (PTSD) has major public health significance. Evidence that PTSD may be associated with premature senescence (early or accelerated aging) would have major implications for quality of life and healthcare policy. We conducted a comprehensive review of published empirical studies relevant to early aging in PTSD. Our search included the PubMed, PsycINFO and PILOTS databases for empirical reports published since the year 2000 relevant to early senescence and PTSD, including: (1) biomarkers of senescence (leukocyte telomere length (LTL) and pro-inflammatory markers), (2) prevalence of senescence-associated medical conditions, and (3) mortality rates. All six studies examining LTL indicated reduced LTL in PTSD (pooled Cohen’s d = 0.76). We also found consistent evidence of increased pro-inflammatory markers in PTSD (mean Cohen’s ds), including C-reactive protein = 0.18, Interleukin-1 beta = 0.44, Interleukin-6 = 0.78, and tumor necrosis factor alpha = 0.81. The majority of reviewed studies also indicated increased medical comorbidity among several targeted conditions known to be associated with normal aging, including cardiovascular disease, type 2 diabetes mellitus, gastrointestinal ulcer disease, and dementia. We also found seven of 10 studies indicated PTSD to be associated with earlier mortality (average HR = 1.29). In short, evidence from multiple lines of investigation suggests that PTSD may be associated with a phenotype of accelerated senescence. Further research is critical to understand the nature of this association. There may be a need to re-conceptualize PTSD beyond the boundaries of mental illness, and instead as a full systemic disorder. PMID:25959921

Oxidative Stress and Antioxidants in the Diagnosis and Therapy of Periodontitis

PubMed Central

Tóthová, L'ubomíra; Celec, Peter

2017-01-01

Oxidative stress has been implicated in the pathogenesis of numerous diseases. However, large interventional studies with antioxidants failed to show benefits in the prevention or treatment of cardiovascular diseases, cancer, or diabetes mellitus. Numerous clinical studies have confirmed the association of oxidative stress markers and periodontitis. Technical and biological variability is high for most of the analyzed markers and none of them seems to be optimal for routine clinical use. In a research setting, analysis of a palette of oxidative stress markers is needed to cover lipid peroxidation, protein oxidation, and the antioxidant status. The source of reactive oxygen species and their role in the pathogenesis of periodontitis remains unclear. Interventional experiments indicate that oxidative stress might be more than just a simple consequence of the inflammation. Small studies have confirmed that some antioxidants could have therapeutic value at least as an addition to the standard non-surgical treatment of periodontitis. A clear evidence for the efficiency of antioxidant treatment in large patient cohorts is lacking. Potentially, because lowering of oxidative stress markers might be a secondary effect of anti-inflammatory or antibacterial agents. As the field of research of oxidative stress in periodontitis gains attraction and the number of relevant published papers is increasing a systematic overview of the conducted observational and interventional studies is needed. This review summarizes the currently available literature linking oxidative stress and periodontitis and points toward the potential of adjuvant antioxidant treatment, especially in cases where standard treatment fails to improve the periodontal status. PMID:29311982

There Is No Coherent Evidence for a Bilingual Advantage in Executive Processing

ERIC Educational Resources Information Center

Paap, Kenneth R.; Greenberg, Zachary I.

2013-01-01

Three studies compared bilinguals to monolinguals on 15 indicators of executive processing (EP). Most of the indicators compare a neutral or congruent baseline to a condition that should require EP. For each of the measures there was no main effect of group and a highly significant main effect of condition. The critical marker for a bilingual…

The (B)link Between Creativity and Dopamine: Spontaneous Eye Blink Rates Predict and Dissociate Divergent and Convergent Thinking

ERIC Educational Resources Information Center

Chermahini, Soghra Akbari; Hommel, Bernhard

2010-01-01

Human creativity has been claimed to rely on the neurotransmitter dopamine, but evidence is still sparse. We studied whether individual performance (N=117) in divergent thinking (alternative uses task) and convergent thinking (remote association task) can be predicted by the individual spontaneous eye blink rate (EBR), a clinical marker of…

Testing for Non-Random Mating: Evidence for Ancestry-Related Assortative Mating in the Framingham Heart Study

PubMed Central

Sebro, Ronnie; Hoffman, Thomas J.; Lange, Christoph; Rogus, John J.; Risch, Neil J.

2013-01-01

Population stratification leads to a predictable phenomenon—a reduction in the number of heterozygotes compared to that calculated assuming Hardy-Weinberg Equilibrium (HWE). We show that population stratification results in another phenomenon—an excess in the proportion of spouse-pairs with the same genotypes at all ancestrally informative markers, resulting in ancestrally related positive assortative mating. We use principal components analysis to show that there is evidence of population stratification within the Framingham Heart Study, and show that the first principal component correlates with a North-South European cline. We then show that the first principal component is highly correlated between spouses (r=0.58, p=0.0013), demonstrating that there is ancestrally related positive assortative mating among the Framingham Caucasian population. We also show that the single nucleotide polymorphisms loading most heavily on the first principal component show an excess of homozygotes within the spouses, consistent with similar ancestry-related assortative mating in the previous generation. This nonrandom mating likely affects genetic structure seen more generally in the North American population of European descent today, and decreases the rate of decay of linkage disequilibrium for ancestrally informative markers. PMID:20842694

Prospective comparison of molecular signatures in urothelial cancer of the bladder and the upper urinary tract--is there evidence for discordant biology?

PubMed

Krabbe, Laura-Maria; Lotan, Yair; Bagrodia, Aditya; Gayed, Bishoy A; Darwish, Oussama M; Youssef, Ramy F; Bolenz, Christian; Sagalowsky, Arthur I; Raj, Ganesh V; Shariat, Shahrokh F; Kapur, Payal; Margulis, Vitaly

2014-04-01

Upper tract urothelial carcinoma is rare and less well studied than bladder cancer. It remains questionable if findings in bladder cancer can safely be extrapolated to upper tract urothelial carcinoma. We prospectively evaluate molecular profiles of upper tract urothelial carcinoma and bladder cancer using a cell cycle biomarker panel. Immunohistochemical staining for p21, p27, p53, cyclin E and Ki-67 was prospectively performed for 96 patients with upper tract urothelial carcinoma and 159 patients with bladder cancer with nonmetastatic high grade urothelial carcinoma treated with extirpative surgery. Data were compared between the groups according to pathological stage. Primary outcome was assessment of differences in marker expression. Secondary outcome was difference in survival according to marker status. During a median followup of 22.0 months 31.2% of patients with upper tract urothelial carcinoma and 28.3% of patients with bladder cancer had disease recurrence, and 20.8% and 27.7% died of upper tract urothelial carcinoma and bladder cancer, respectively. The number of altered markers was not significantly different between the study groups. Overall 34 patients (35.4%) with upper tract urothelial carcinoma and 62 (39.0%) with bladder cancer had an unfavorable marker score (more than 2 markers altered). There were no significant differences between upper tract urothelial carcinoma and bladder cancer in the alteration status of markers, the number of altered markers and biomarker score when substratified by pathological stage. There were no significant differences in survival outcomes between patients with upper tract urothelial carcinoma and those with bladder cancer according to the number of altered markers and biomarker score. Our results demonstrate the molecular similarity of upper tract urothelial carcinoma and bladder cancer in terms of cell cycle and proliferative tissue markers. These findings have important implications and support the further extrapolation of treatment paradigms established in bladder cancer to upper tract urothelial carcinoma. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Hyper-insulinaemia and cancer, meta-analyses of epidemiological studies.

PubMed

Pisani, Paola

2008-02-01

A substantial body of evidence links sex hormones, diet, excess body weight and physical activity to the risk of developing cancer at several sites common in affluent countries. The hypothesis that high circulating levels of insulin could be the underlying factor increasing cancer risk has been proposed. Epidemiological studies on markers of hyper-insulinaemia and cancer are reviewed and summarized. Studies of cancers of the colon and rectum, pancreas, breast, and endometrium examining the association with blood levels of C-peptide, insulin, glucose, glycated haemoglobin (HbA1c) were searched in PubMed. Multivariate, adjusted relative risks (RR) and their 95% confidence intervals were abstracted and summarized by meta-analyses. Most of the studies identified were cohorts that relied on measurements obtained at baseline or assessed in blood stored at low temperature several years before the onset of cancer. The meta-analyses showed excess risks of colorectal and pancreatic cancers associated with higher levels of circulating C-peptide/insulin and with markers of glycaemia. Significant heterogeneity was found among four epidemiological studies of endometrial cancer and C-peptide giving a summary RR compatible with no association. Overall breast cancer risk was significantly higher in the upper categories of C-peptide/insulin, however, the excess derived entirely from retrospective studies. Current evidence suggests that subjects who develop colorectal and pancreatic cancers have increased pre-diagnostic blood levels of insulin and glucose.

Application of plant DNA markers in forensic botany: genetic comparison of Quercus evidence leaves to crime scene trees using microsatellites.

PubMed

Craft, Kathleen J; Owens, Jeffrey D; Ashley, Mary V

2007-01-05

As highly polymorphic DNA markers become increasingly available for a wide range of plant and animal species, there will be increasing opportunities for applications to forensic investigations. To date, however, relatively few studies have reported using DNA profiles of non-human species to place suspects at or near crime scenes. Here we describe an investigation of a double homicide of a female and her near-term fetus. Leaf material taken from a suspect's vehicle was identified to be that of sand live oak, Quercus geminata, the same tree species that occurred near a shallow grave where the victims were found. Quercus-specific DNA microsatellites were used to genotype both dried and fresh material from trees located near the burial site and from the material taken from the suspect's car. Samples from the local population of Q. geminata were also collected and genotyped in order to demonstrate that genetic variation at four microsatellite loci was sufficient to assign leaves to an individual tree with high statistical certainty. The cumulative average probability of identity for these four loci was 2.06x10(-6). DNA was successfully obtained from the dried leaf material although PCR amplification was more difficult than amplification of DNA from fresh leaves. The DNA profiles of the dried leaves from the suspect's car did not match those of the trees near the crime scene. Although this investigation did not provide evidence that could be used against the suspect, it does demonstrate the potential for plant microsatellite markers providing physical evidence that links plant materials to live plants at or near crime scenes.

Exploring the Q-marker of "sweat soaking method" processed radix Wikstroemia indica: Based on the "effect-toxicity-chemicals" study.

PubMed

Feng, Guo; Chen, Yun-Long; Li, Wei; Li, Lai-Lai; Wu, Zeng-Guang; Wu, Zi-Jun; Hai, Yue; Zhang, Si-Chao; Zheng, Chuan-Qi; Liu, Chang-Xiao; He, Xin

2018-06-01

Radix Wikstroemia indica (RWI), named "Liao Ge Wang" in Chinese, is a kind of toxic Chinese herbal medicine (CHM) commonly used in Miao nationality of South China. "Sweat soaking method" processed RWI could effectively decrease its toxicity and preserve therapeutic effect. However, the underlying mechanism of processing is still not clear, and the Q-markers database for processed RWI has not been established. Our study is to investigate and establish the quality evaluation system and potential Q-markers based on "effect-toxicity-chemicals" relationship of RWI for quality/safety assessment of "sweat soaking method" processing. The variation of RWI in efficacy and toxicity before and after processing was investigated by pharmacological and toxicological studies. Cytotoxicity test was used to screen the cytotoxicity of components in RWI. The material basis in ethanol extract of raw and processed RWI was studied by UPLC-Q-TOF/MS. And the potential Q-markers were analyzed and predicted according to "effect-toxicity-chemical" relationship. RWI was processed by "sweat soaking method", which could preserve efficacy and reduce toxicity. Raw RWI and processed RWI did not show significant difference on the antinociceptive and anti-inflammatory effect, however, the injury of liver and kidney by processed RWI was much weaker than that by raw RWI. The 20 compounds were identified from the ethanol extract of raw product and processed product of RWI using UPLC-Q-TOF/MS, including daphnoretin, emodin, triumbelletin, dibutyl phthalate, Methyl Paraben, YH-10 + OH and matairesinol, arctigenin, kaempferol and physcion. Furthermore, 3 diterpenoids (YH-10, YH-12 and YH-15) were proved to possess the high toxicity and decreased by 48%, 44% and 65%, respectively, which could be regarded as the potential Q-markers for quality/safety assessment of "sweat soaking method" processed RWI. A Q-marker database of processed RWI by "sweat soaking method" was established according to the results and relationship of "effect-toxicity-chemicals", which provided a scientific evidence for processing methods, mechanism and the clinical application of RWI, also provided experimental results to explore the application of Q-marker in CHM. Copyright © 2018 Elsevier GmbH. All rights reserved.

Branched-chain and aromatic amino acid profiles and diabetes risk in Chinese populations.

PubMed

Chen, Tianlu; Ni, Yan; Ma, Xiaojing; Bao, Yuqian; Liu, Jiajian; Huang, Fengjie; Hu, Cheng; Xie, Guoxiang; Zhao, Aihua; Jia, Weiping; Jia, Wei

2016-02-05

Recent studies revealed strong evidence that branched-chain and aromatic amino acids (BCAAs and AAAs) are closely associated with the risk of developing type 2 diabetes in several Western countries. The aim of this study was to evaluate the potential role of BCAAs and AAAs in predicting the diabetes development in Chinese populations. The serum levels of valine, leucine, isoleucine, tyrosine, and phenylalanine were measured in a longitudinal and a cross sectional studies with a total of 429 Chinese participants at different stages of diabetes development, using an ultra-performance liquid chromatography triple quadruple mass spectrometry platform. The alterations of the five AAs in Chinese populations are well in accordance with previous reports. Early elevation of the five AAs and their combined score was closely associated with future development of diabetes, suggesting an important role of these metabolites as early markers of diabetes. On the other hand, the five AAs were not as good as existing clinical markers in differentiating diabetic patients from their healthy counterparts. Our findings verified the close correlation of BCAAs and AAAs with insulin resistance and future development of diabetes in Chinese populations and highlighted the predictive value of these markers for future development of diabetes.

Branched-chain and aromatic amino acid profiles and diabetes risk in Chinese populations

PubMed Central

Chen, Tianlu; Ni, Yan; Ma, Xiaojing; Bao, Yuqian; Liu, Jiajian; Huang, Fengjie; Hu, Cheng; Xie, Guoxiang; Zhao, Aihua; Jia, Weiping; Jia, Wei

2016-01-01

Recent studies revealed strong evidence that branched-chain and aromatic amino acids (BCAAs and AAAs) are closely associated with the risk of developing type 2 diabetes in several Western countries. The aim of this study was to evaluate the potential role of BCAAs and AAAs in predicting the diabetes development in Chinese populations. The serum levels of valine, leucine, isoleucine, tyrosine, and phenylalanine were measured in a longitudinal and a cross sectional studies with a total of 429 Chinese participants at different stages of diabetes development, using an ultra-performance liquid chromatography triple quadruple mass spectrometry platform. The alterations of the five AAs in Chinese populations are well in accordance with previous reports. Early elevation of the five AAs and their combined score was closely associated with future development of diabetes, suggesting an important role of these metabolites as early markers of diabetes. On the other hand, the five AAs were not as good as existing clinical markers in differentiating diabetic patients from their healthy counterparts. Our findings verified the close correlation of BCAAs and AAAs with insulin resistance and future development of diabetes in Chinese populations and highlighted the predictive value of these markers for future development of diabetes. PMID:26846565

Methods to determine metabolizable energy and digestibility of feed ingredients in the domestic pigeon (Columba livia domestica).

PubMed

Sales, J; Janssens, G P J

2003-09-01

The influence of length of excreta collection period (1, 3, 6, 10, 14 d) and prefeeding protocol (7 d either individual feeding in collection cages or group feeding in housing cages) on AMEn, nitrogen retention (NR), and apparent DM, organic matter and ether extract digestibility of corn and peas were evaluated in domestic pigeons (Columba livia domestica). In addition, the use of internal markers [acid-insoluble ash (AIA) and acid detergent lignin (ADL)] to determine AMEn, NR, and apparent digestibility was compared with the method of measuring total feed input and excreta output. A quadratic (y = a + bx + cx2) trend in the CV for AMEn, NR, and apparent digestibility coefficients found over collection periods with corn presented evidence that excreta collection for a period of 3 d will produce a CV of 5% less than the minimum CV. Although no trend could be detected in CV for peas, a 3-d excreta collection period resulted in relatively low variation. Both AIA and ADL, when used as internal markers, resulted in AMEn, NR, and digestibility values below (P < 0.05) those obtained with total collection with corn. However, values between markers were comparable (P > 0.05) for all components evaluated. The ADL was unsuccessful as marker with peas. Group prefeeding of pigeons in housing cages resulted in lower feed intake, excreta output, NR, and apparent digestibility than when birds were adapted individually to collection cages. This study presents evidence that the method of measuring total feed intake and excreta output for a period of 3 d, with individual adaptation of birds to collection cages, resulted in the most reliable values for AMEn, NR, and apparent digestibility of DM, organic matter and ether extract of feed ingredients in pigeons.

Semi-quantitative evaluation of fecal contamination potential by human and ruminant sources using multiple lines of evidence

USGS Publications Warehouse

Stoeckel, D.M.; Stelzer, E.A.; Stogner, R.W.; Mau, D.P.

2011-01-01

Protocols for microbial source tracking of fecal contamination generally are able to identify when a source of contamination is present, but thus far have been unable to evaluate what portion of fecal-indicator bacteria (FIB) came from various sources. A mathematical approach to estimate relative amounts of FIB, such as Escherichia coli, from various sources based on the concentration and distribution of microbial source tracking markers in feces was developed. The approach was tested using dilute fecal suspensions, then applied as part of an analytical suite to a contaminated headwater stream in the Rocky Mountains (Upper Fountain Creek, Colorado). In one single-source fecal suspension, a source that was not present could not be excluded because of incomplete marker specificity; however, human and ruminant sources were detected whenever they were present. In the mixed-feces suspension (pet and human), the minority contributor (human) was detected at a concentration low enough to preclude human contamination as the dominant source of E. coli to the sample. Without the semi-quantitative approach described, simple detects of human-associated marker in stream samples would have provided inaccurate evidence that human contamination was a major source of E. coli to the stream. In samples from Upper Fountain Creek the pattern of E. coli, general and host-associated microbial source tracking markers, nutrients, and wastewater-associated chemical detections-augmented with local observations and land-use patterns-indicated that, contrary to expectations, birds rather than humans or ruminants were the predominant source of fecal contamination to Upper Fountain Creek. This new approach to E. coli allocation, validated by a controlled study and tested by application in a relatively simple setting, represents a widely applicable step forward in the field of microbial source tracking of fecal contamination. ?? 2011 Elsevier Ltd.

Changes in cognitive functions and cerebral grey matter and their associations with inflammatory markers, endocrine markers, and APOE genotypes in testicular cancer patients undergoing treatment.

PubMed

Amidi, Ali; Agerbæk, Mads; Wu, Lisa M; Pedersen, Anders D; Mehlsen, Mimi; Clausen, Cecilie R; Demontis, Ditte; Børglum, Anders D; Harbøll, Anja; Zachariae, Robert

2017-06-01

Evidence suggests that testicular cancer (TC) and its treatment are associated with cognitive impairment. However, the underlying neural substrate and biological mechanisms are poorly understood. This study aimed to investigate changes in cognition and brain grey matter (GM) morphology in TC patients undergoing treatment, and to explore associations with immune markers, endocrine markers, and genotype. Sixty-five patients with stage I-III TC underwent assessment after surgery but prior to further treatment and again 6 months after. Twenty-two patients received chemotherapy (+CT), while 43 did not (-CT). Assessments included neuropsychological testing, whole-brain magnetic resonance imaging, and blood samples. Twenty-five healthy controls (HCs) underwent neuropsychological testing with a matching time interval. A regression-based approach was used to determine cognitive changes and longitudinal voxel-based morphometry (VBM) was performed to investigate changes in GM density in the TC groups. Compared with the HCs, both TC groups showed higher rates of cognitive decline (p < 0.05). A trend towards greater decline was observed in + CT (63.6 %) compared with -CT patients (39.5 %) (p = 0.07). VBM revealed widespread GM reductions in both TC groups, but a group-by-time interaction analysis revealed prefrontal reductions specific to the + CT group (p = 0.02), which were associated with poorer cognitive performance. Poorer cognitive performance was also associated with an increase in tumor necrosis factor alpha in + CT patients. Furthermore, an interaction effect was found between the APOE ε4 genotype and chemotherapy on cognitive performance with ε4 carriers performing significantly worse. These findings provide novel evidence of changes in cognition and brain morphology in TC patients undergoing treatment.

Combined Socio-Behavioral Evaluation Improves the Differential Diagnosis Between the Behavioral Variant of Frontotemporal Dementia and Alzheimer's Disease: In Search of Neuropsychological Markers.

PubMed

Dodich, Alessandra; Cerami, Chiara; Cappa, Stefano F; Marcone, Alessandra; Golzi, Valeria; Zamboni, Michele; Giusti, Maria Cristina; Iannaccone, Sandro

2018-01-01

Current diagnostic criteria for behavioral variant of frontotemporal dementia (bvFTD) and typical Alzheimer's disease (AD) include a differential pattern of neuropsychological impairments (episodic memory deficit in typical AD and dysexecutive syndrome in bvFTD). There is, however, large evidence of a frequent overlap in neuropsychological features, making the differential diagnosis extremely difficult. In this retrospective study, we evaluated the diagnostic value of different cognitive and neurobehavioral markers in bvFTD and AD patient groups. We included 95 dementia patients with a clinical and biomarker evidence of bvFTD (n = 48) or typical AD (n = 47) pathology. A clinical 2-year follow-up confirmed clinical classification. Performances at basic cognitive tasks (memory, executive functions, visuo-spatial, language) as well as social cognition skills and neurobehavioral profiles have been recorded. A stepwise logistic regression model compared the neuropsychological profiles between groups and assessed the accuracy of cognitive and neurobehavioral markers in discriminating bvFTD from AD. Statistical comparison between patient groups proved social cognition and episodic memory impairments as main cognitive signatures of bvFTD and AD neuropsychological profiles, respectively. Only half of bvFTD patients showed attentive/executive deficits, questioning their role as cognitive marker of bvFTD. Notably, the large majority of bvFTD sample (i.e., 70%) poorly performed at delayed recall tasks. Logistic regression analysis identified social cognition performances, Frontal Behavioral Inventory and Mini-Mental State Examination scores as the best combination in distinguishing bvFTD from AD. Social cognition tasks and socio-behavioral questionnaires are recommended in clinical settings to improve the accuracy of early diagnosis of bvFTD.

Chronic inflammation is a feature of Achilles tendinopathy and rupture.

PubMed

Dakin, Stephanie Georgina; Newton, Julia; Martinez, Fernando O; Hedley, Robert; Gwilym, Stephen; Jones, Natasha; Reid, Hamish A B; Wood, Simon; Wells, Graham; Appleton, Louise; Wheway, Kim; Watkins, Bridget; Carr, Andrew Jonathan

2018-03-01

Recent investigation of human tissue and cells from positional tendons such as the rotator cuff has clarified the importance of inflammation in the development and progression of tendon disease. These mechanisms remain poorly understood in disease of energy-storing tendons such as the Achilles. Using tissue biopsies from patients, we investigated if inflammation is a feature of Achilles tendinopathy and rupture. We studied Achilles tendon biopsies from symptomatic patients with either mid-portion tendinopathy or rupture for evidence of abnormal inflammatory signatures. Tendon-derived stromal cells from healthy hamstring and diseased Achilles were cultured to determine the effects of cytokine treatment on expression of inflammatory markers. Tendinopathic and ruptured Achilles highly expressed CD14+ and CD68+ cells and showed a complex inflammation signature, involving NF-κB, interferon and STAT-6 activation pathways. Interferon markers IRF1 and IRF5 were highly expressed in tendinopathic samples. Achilles ruptures showed increased PTGS2 and interleukin-8 expression. Tendinopathic and ruptured Achilles tissues expressed stromal fibroblast activation markers podoplanin and CD106. Tendon cells isolated from diseased Achilles showed increased expression of pro-inflammatory and stromal fibroblast activation markers after cytokine stimulation compared with healthy hamstring tendon cells. Tissue and cells derived from tendinopathic and ruptured Achilles tendons show evidence of chronic (non-resolving) inflammation. The energy-storing Achilles shares common cellular and molecular inflammatory mechanisms with functionally distinct rotator cuff positional tendons. Differences seen in the profile of ruptured Achilles are likely to be attributable to a superimposed phase of acute inflammation and neo-vascularisation. Strategies that target chronic inflammation are of potential therapeutic benefit for patients with Achilles tendon disease. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Chronic inflammation is a feature of Achilles tendinopathy and rupture

PubMed Central

Newton, Julia; Martinez, Fernando O; Hedley, Robert; Gwilym, Stephen; Jones, Natasha; Reid, Hamish A B; Wood, Simon; Wells, Graham; Appleton, Louise; Wheway, Kim; Watkins, Bridget; Carr, Andrew Jonathan

2018-01-01

Background Recent investigation of human tissue and cells from positional tendons such as the rotator cuff has clarified the importance of inflammation in the development and progression of tendon disease. These mechanisms remain poorly understood in disease of energy-storing tendons such as the Achilles. Using tissue biopsies from patients, we investigated if inflammation is a feature of Achilles tendinopathy and rupture. Methods We studied Achilles tendon biopsies from symptomatic patients with either mid-portion tendinopathy or rupture for evidence of abnormal inflammatory signatures. Tendon-derived stromal cells from healthy hamstring and diseased Achilles were cultured to determine the effects of cytokine treatment on expression of inflammatory markers. Results Tendinopathic and ruptured Achilles highly expressed CD14+ and CD68+ cells and showed a complex inflammation signature, involving NF-κB, interferon and STAT-6 activation pathways. Interferon markers IRF1 and IRF5 were highly expressed in tendinopathic samples. Achilles ruptures showed increased PTGS2 and interleukin-8 expression. Tendinopathic and ruptured Achilles tissues expressed stromal fibroblast activation markers podoplanin and CD106. Tendon cells isolated from diseased Achilles showed increased expression of pro-inflammatory and stromal fibroblast activation markers after cytokine stimulation compared with healthy hamstring tendon cells. Conclusions Tissue and cells derived from tendinopathic and ruptured Achilles tendons show evidence of chronic (non-resolving) inflammation. The energy-storing Achilles shares common cellular and molecular inflammatory mechanisms with functionally distinct rotator cuff positional tendons. Differences seen in the profile of ruptured Achilles are likely to be attributable to a superimposed phase of acute inflammation and neo-vascularisation. Strategies that target chronic inflammation are of potential therapeutic benefit for patients with Achilles tendon disease. PMID:29118051

Safe and stable noninvasive focal gene delivery to the mammalian brain following focused ultrasound.

PubMed

Stavarache, Mihaela A; Petersen, Nicholas; Jurgens, Eric M; Milstein, Elizabeth R; Rosenfeld, Zachary B; Ballon, Douglas J; Kaplitt, Michael G

2018-04-27

OBJECTIVE Surgical infusion of gene therapy vectors has provided opportunities for biological manipulation of specific brain circuits in both animal models and human patients. Transient focal opening of the blood-brain barrier (BBB) by MR-guided focused ultrasound (MRgFUS) raises the possibility of noninvasive CNS gene therapy to target precise brain regions. However, variable efficiency and short follow-up of studies to date, along with recent suggestions of the potential for immune reactions following MRgFUS BBB disruption, all raise questions regarding the viability of this approach for clinical translation. The objective of the current study was to evaluate the efficiency, safety, and long-term stability of MRgFUS-mediated noninvasive gene therapy in the mammalian brain. METHODS Focused ultrasound under the control of MRI, in combination with microbubbles consisting of albumin-coated gas microspheres, was applied to rat striatum, followed by intravenous infusion of an adeno-associated virus serotype 1/2 (AAV1/2) vector expressing green fluorescent protein (GFP) as a marker. Following recovery, animals were followed from several hours up to 15 months. Immunostaining for GFP quantified transduction efficiency and stability of expression. Quantification of neuronal markers was used to determine histological safety over time, while inflammatory markers were examined for evidence of immune responses. RESULTS Transitory disruption of the BBB by MRgFUS resulted in efficient delivery of the AAV1/2 vector to the targeted rodent striatum, with 50%-75% of striatal neurons transduced on average. GFP transgene expression appeared to be stable over extended periods of time, from 2 weeks to 6 months, with evidence of ongoing stable expression as long as 16 months in a smaller cohort of animals. No evidence of substantial toxicity, tissue injury, or neuronal loss was observed. While transient inflammation from BBB disruption alone was noted for the first few days, consistent with prior observations, no evidence of brain inflammation was observed from 2 weeks to 6 months following MRgFUS BBB opening, despite delivery of a virus and expression of a foreign protein in target neurons. CONCLUSIONS This study demonstrates that transitory BBB disruption using MRgFUS can be a safe and efficient method for site-specific delivery of viral vectors to the brain, raising the potential for noninvasive focal human gene therapy for neurological disorders.

Sex-specific markers developed by next-generation sequencing confirmed an XX/XY sex determination system in bighead carp (Hypophthalmichehys nobilis) and silver carp (Hypophthalmichthys molitrix).

PubMed

Liu, Haiyang; Pang, Meixia; Yu, Xiaomu; Zhou, Ying; Tong, Jingou; Fu, Beide

2018-01-05

Sex-specific markers are powerful tools for identifying sex-determination system in various animals. Bighead carp (Hypophthalmichehys nobilis) and silver carp (Hypophthalmichthys molitrix) are two of the most important edible fish in Asia, which have a long juvenility period that can lasts for 4-5 years. In this study, we found one sex-specific marker by next-generation sequencing together with bioinformatics analysis in bighead carp. The male-specific markers were used to perform molecular sexing in the progenies of artificial gynogenetic diploids and found all progenies (n = 160) were females. Meanwhile, around 1 : 1 sex ratio was observed in a total of 579 juvenile offspring from three other families. To further extend the male-specific region, we performed genome walking and got a male-specific sequence of 8,661 bp. Five pairs of primers were designed and could be used to efficiently distinguish males from females in bighead carp and silver carp. The development of these male-specific markers and results of their molecular sexing in different populations provide strong evidence for a sex determination system of female homogametry or male heterogametry (XX/XY) in bighead carp and silver carp. To the best of our knowledge, this is the first report of effective sex-specific markers in these two large carp species. © The Author(s) 2018. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

Archaeological implications of a widespread 13th Century tephra marker across the central Indonesian Archipelago

NASA Astrophysics Data System (ADS)

Alloway, Brent V.; Andreastuti, Supriyati; Setiawan, Ruly; Miksic, John; Hua, Quan

2017-01-01

Despite the occurrence of exceptionally large eruptions in the Indonesian Archipelago in recent historic times (i.e. Krakatoa 1883, Tambora 1815), no historic tephra beds have been widely identified in the terrestrial realm that could facilitate the correlation of equivalent aged sequences and/or archaeological remains. This study has identified one such tephra bed of 13th Century age that can be correlated throughout central-east Java and now can be unequivocally correlated with the Samalas 1257 A.D. tephra recently described from Lombok. The occurrence of this historic tephra marker extending ≥650 km west from its eruptive source provides the first opportunity to effect inter-regional correlation over large swathes of central Indonesia. It remains entirely conceivable that in the aftermath of this exceptionally large eruptive event there was considerable westward disruption to subsistence agriculture and trade, food shortages and famine, dislocation of affected populations and socio-political unrest on a scale that equalled or exceeded the catastrophic effects documented from the more recent Tambora 1815 A.D. eruption. Indeed the effects of this mid-13th Century eruption can be registered globally in a variety of records from Antarctica, Europe, Middle East and the Americas. Unfortunately, archaeological evidence indicating such disruption in mid-13th Century Indonesia is yet to be deciphered from the so-far sparse accounts and inscriptions of that time. However, this paucity of evidence does not diminish the utility of this widespread tephra bed as a unique chronostratigraphic marker for archaeological studies across large areas of central Indonesia.

Double product and end-organ damage in African and Caucasian men: the SABPA study.

PubMed

Schultz, A J; Schutte, A E; Schutte, R

2013-08-10

Increasing urbanisation in sub-Saharan African countries is causing a rapid increase in cardiovascular disease. Evidence suggests that Africans have higher blood pressures and a higher prevalence of hypertension-related cardiovascular morbidity and mortality, compared to Caucasians. We investigated double product (systolic blood pressure × heart rate), a substantial measure of cardiac workload, as a possible cardiovascular risk factor in African and Caucasian men. The study consisted of 101 urbanised African and 101 Caucasian male school teachers. We measured 24h ambulatory blood pressure and the carotid cross-sectional wall area, and determined left ventricular hypertrophy electrocardiographically by means of the Cornell product. Urinary albumin and creatinine were analysed to obtain the albumin-to-creatinine ratio. Africans had higher 24h, daytime and nighttime systolic- and diastolic blood pressure, heart rate and resultant double product compared to the Caucasians. In addition, markers of end-organ damage, albumin-to-creatinine ratio and left ventricular hypertrophy were higher in the Africans while cross-sectional wall area did not differ. In Africans after single partial and multiple regression analysis, 24h systolic blood pressure, but not double product or heart rate, correlated positively with markers of end-organ damage (cross-sectional wall area: β=0.398, P=0.005; left ventricular hypertrophy: β=0.455, P<0.001; albumin-to-creatinine ratio: β=0.280, P=0.012). No associations were evident in Caucasian men. Double product may not be a good marker of increased cardiovascular risk when compared to systolic blood pressure in African and Caucasian men. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Reassessing the Ancient Martian Ocean Hypothesis using Global Distribution of Valley Networks

NASA Astrophysics Data System (ADS)

Chan, Ngai-Ham; Perron, J. Taylor; Mitrovica, Jerry X.

2016-04-01

We re-examine the connection between true polar wander and the Martian ocean hypothesis. Previous studies have investigated the plausibility of an ancient ocean on Mars by examining the ancient putative sea-level markers on the planet's surface. One such study has argued that topographic benches, or contacts, are ancient shorelines, and that these contacts display long-wavelength topographic variations consistent with post-depositional true polar wander (Perron et al., Nature, 2007). In contrast, a second study has argued that the topography of ancient deltaic deposits associated with an ocean on early Mars are not consistent with the true polar wander scenario (Achille & Hynek, Nature Geosci., 2010). We revisit this issue by examining another marker of ancient shorelines --- the fluvial valley networks observed on the surface of Mars. Our results provide further evidence that a true polar wander event drove significant post-depositional deflection of surface features related to an ancient Martian ocean.

Reassessing the Ancient Martian Ocean Hypothesis using Global Distribution of Valley Networks

NASA Astrophysics Data System (ADS)

Chan, N. H.; Perron, J. T.; Mitrovica, J. X.

2015-12-01

We re-examine the connection between true polar wander and the Martian ocean hypothesis. Previous studies have investigated the plausibility of an ancient ocean on Mars by examining the topography of ancient putative sea-level markers on the planet's surface. A previous study has argued that topographic benches, or contacts, are ancient shorelines, and that these contacts display long-wavelength topographic variations consistent with post-depositional true polar wander (Perron et al., Nature, 2007). In contrast, a second study has argued that the topography of ancient deltaic deposits associated with an ocean on early Mars are not consistent with the true polar wander scenario (Achille & Hynek, Nature Geosci., 2010). We revisit this issue by examining another marker of ancient shorelines --- the fluvial valley networks observed on the surface of Mars. Our results provide further evidence that a true polar wander event drove significant post-depositional deflection of surface features related to an ancient Martian ocean.

The beat of social cognition: Exploring the role of heart rate variability as marker of mentalizing abilities.

PubMed

Okruszek, Łukasz; Dolan, Kirsty; Lawrence, Megan; Cella, Matteo

2017-10-01

There is a long-standing debate on the influence of physiological signals on social behavior. Recent studies suggested that heart rate variability (HRV) may be a marker of social cognitive processes. However, this evidence is preliminary and limited to laboratory studies. In this study, 25 participants were assessed with a social cognition battery and asked to wear a wearable device measuring HRV for 6 consecutive days. The results showed that reduced HRV correlated with higher hostility attribution bias. However, no relationship was found between HRV and other social cognitive measures including facial emotion recognition, theory of mind or emotional intelligence. These results suggest that HRV may be linked to specific social cognitive processes requiring online emotional processing, in particular those related to social threat. These findings are discussed in the context of the neurovisceral integration model.

Problems with mitochondrial DNA as a marker in population, phylogeographic and phylogenetic studies: the effects of inherited symbionts

PubMed Central

Hurst, Gregory D.D; Jiggins, Francis M

2005-01-01

Mitochondrial DNA (mtDNA) has been a marker of choice for reconstructing historical patterns of population demography, admixture, biogeography and speciation. However, it has recently been suggested that the pervasive nature of direct and indirect selection on this molecule renders any conclusion derived from it ambiguous. We review here the evidence for indirect selection on mtDNA in arthropods arising from linkage disequilibrium with maternally inherited symbionts. We note first that these symbionts are very common in arthropods and then review studies that reveal the extent to which they shape mtDNA evolution. mtDNA diversity patterns are compatible with neutral expectations for an uninfected population in only 2 of 19 cases. The remaining 17 studies revealed cases of symbiont-driven reduction in mtDNA diversity, symbiont-driven increases in diversity, symbiont-driven changes in mtDNA variation over space and symbiont-associated paraphyly of mtDNA. We therefore conclude that these elements often confound the inference of an organism's evolutionary history from mtDNA data and that mtDNA on its own is an unsuitable marker for the study of recent historical events in arthropods. We also discuss the impact of these studies on the current programme of taxonomy based on DNA bar-coding. PMID:16048766

FAT10 IS AN EPIGENETIC MARKER FOR LIVER PRENEOPLASIA IN A DRUG-PRIMED MOUSE MODEL OF TUMORIGENESIS

PubMed Central

Oliva, Joan; Bardag-Gorce, Fawzia; French, Barbara A; Li, Jun; McPhaul, Laron; Amidi, Fataneh; Dedes, Jeniffer; Habibi, Amir; Nguyen, Sheila; French, Samuel W

2010-01-01

There is clinical evidence that chronic liver diseases in which MDBs (Mallory Denk Bodies) form progress to hepatocellular carcinoma. The present study provides evidence that links MDB formation induced by chronic drug injury, with preneoplasia and later to the formation of tumors, which develop long after drug withdrawal. Evidence indicated that this link was due to an epigenetic cellular memory induced by chronic drug ingestion. Microarray analysis showed that the expressions of many markers of preneoplasia (UBD, Alpha Fetoprotein, KLF6 and Glutathione-S-Transferase mu2) were increased together when the drug DDC was refed. These changes were suppressed by S-adenosylmethionine feeding, indicating that the drug was affecting DNA and histones methylation in an epigenetic manner. The link between MDB formation and neoplasia formation was likely due to the over expression of UBD (also called FAT10), which is up regulated in 90% of human hepatocellular carcinomas. Immunohistochemical staining of drug primed mouse livers showed that FAT10 positive liver cells persisted up to 4 months after drug withdrawal and they were still found in the livers of mice, 14 months after drug withdrawal. The refeeding of DDC increased the percent of FAT10 hepatocytes. PMID:18280469

Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury

PubMed Central

2013-01-01

Introduction Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. Methods We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. Results Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P <0.002), none of which achieved an AUC >0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method. Conclusions Two novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI. Trial registration ClinicalTrials.gov number NCT01209169. PMID:23388612

The Biomarker-Surrogacy Evaluation Schema: a review of the biomarker-surrogate literature and a proposal for a criterion-based, quantitative, multidimensional hierarchical levels of evidence schema for evaluating the status of biomarkers as surrogate endpoints.

PubMed

Lassere, Marissa N

2008-06-01

There are clear advantages to using biomarkers and surrogate endpoints, but concerns about clinical and statistical validity and systematic methods to evaluate these aspects hinder their efficient application. Section 2 is a systematic, historical review of the biomarker-surrogate endpoint literature with special reference to the nomenclature, the systems of classification and statistical methods developed for their evaluation. In Section 3 an explicit, criterion-based, quantitative, multidimensional hierarchical levels of evidence schema - Biomarker-Surrogacy Evaluation Schema - is proposed to evaluate and co-ordinate the multiple dimensions (biological, epidemiological, statistical, clinical trial and risk-benefit evidence) of the biomarker clinical endpoint relationships. The schema systematically evaluates and ranks the surrogacy status of biomarkers and surrogate endpoints using defined levels of evidence. The schema incorporates the three independent domains: Study Design, Target Outcome and Statistical Evaluation. Each domain has items ranked from zero to five. An additional category called Penalties incorporates additional considerations of biological plausibility, risk-benefit and generalizability. The total score (0-15) determines the level of evidence, with Level 1 the strongest and Level 5 the weakest. The term ;surrogate' is restricted to markers attaining Levels 1 or 2 only. Surrogacy status of markers can then be directly compared within and across different areas of medicine to guide individual, trial-based or drug-development decisions. This schema would facilitate communication between clinical, researcher, regulatory, industry and consumer participants necessary for evaluation of the biomarker-surrogate-clinical endpoint relationship in their different settings.

Peripheral inflammatory markers in amnestic mild cognitive impairment.

PubMed

Karim, Salman; Hopkins, Steve; Purandare, Nitin; Crowther, Jackie; Morris, Julie; Tyrrell, Pippa; Burns, Alistair

2014-03-01

To prospectively monitor plasma inflammatory marker concentrations in peripheral blood, over 12 months, in subjects with amnestic mild cognitive impairment (MCI), and to determine the relationship between peripheral inflammatory markers and cognitive decline. Seventy patients with amnestic MCI were recruited from two sites providing specialist memory assessment services in Manchester. The baseline assessment included physical examination, neuro-psychological testing and venous blood samples for C-reactive protein (CRP) and interleukin 6 (IL-6) concentrations. Sixty two participants were followed up after 12 months and the assessments were repeated. Data analysis revealed a significant rise in CRP, but not IL-6 concentrations over 12 months, which was not confounded by demographic variables. The neuro-psychological test scores had no association with CRP or IL-6 concentrations at baseline or 12 months follow-up. This study adopted the unique approach of prospectively investigating peripheral inflammatory markers in a cohort with amnestic MCI. A significant rise in CRP concentrations over 12 months, but lack of significant association with cognition, provide no evidence for a relationship between systemic inflammation and cognitive decline in amnestic MCI. © 2013 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons, Ltd.

Marker chromosome genomic structure and temporal origin implicate a chromoanasynthesis event in a family with pleiotropic psychiatric phenotypes.

PubMed

Grochowski, Christopher M; Gu, Shen; Yuan, Bo; Tcw, Julia; Brennand, Kristen J; Sebat, Jonathan; Malhotra, Dheeraj; McCarthy, Shane; Rudolph, Uwe; Lindstrand, Anna; Chong, Zechen; Levy, Deborah L; Lupski, James R; Carvalho, Claudia M B

2018-04-25

Small supernumerary marker chromosomes (sSMC) are chromosomal fragments difficult to characterize genomically. Here, we detail a proband with schizoaffective disorder and a mother with bipolar disorder with psychotic features who present with a marker chromosome that segregates with disease. We explored the architecture of this marker and investigated its temporal origin. Array comparative genomic hybridization (aCGH) analysis revealed three duplications and three triplications that spanned the short arm of chromosome 9, suggestive of a chromoanasynthesis-like event. Segregation of marker genotypes, phased using sSMC mosaicism in the mother, provided evidence that it was generated during a germline-level event in the proband's maternal grandmother. Whole-genome sequencing (WGS) was performed to resolve the structure and junctions of the chromosomal fragments, revealing further complexities. While structural variations have been previously associated with neuropsychiatric disorders and marker chromosomes, here we detail the precise architecture, human life-cycle genesis, and propose a DNA replicative/repair mechanism underlying formation. © 2018 Wiley Periodicals, Inc.

[History of tumor markers for cancers of the digestive system].

PubMed

Buzás, György Miklós

2013-05-26

Tumor markers are gene products which signal the occurrence of tumors in different organs as well as their response to surgery and chemotherapy. The discovery of tumor markers occurred after the demonstration of tumor-specific transplantation antigens in chemically or virally induced tumors in syngenic rodents. The history of currently used tumor markers began in the 1940s, the first discovered being alpha-fetoprotein in 1956, followed by that of carcinoembryonic antigen in 1965. Since then the range of tumor markers has widened continously. Their chemical structure and genetics is now well known. Some may play part in tumor growth and development of metastases. The potential uses of tumor markers are general or high risk population screening, adjunct in diagnosis of cancer, preoperative indicator of tumor burden, indicator of therapeutic success, evidence of postoperative recurrences and use in tumor localization. However, there is no ideal tumor marker fulfilling all the criteria. Isotope-labeled anti-carcinoembryonic antigen antibodies and small molecular E-selectin inhibitors could play a role in the molecular radio- and chemotherapy of colon and pancreatic carcinomas.

A grass molecular identification system for forensic botany: a critical evaluation of the strengths and limitations.

PubMed

Ward, Jodie; Gilmore, Simon R; Robertson, James; Peakall, Rod

2009-11-01

Plant material is frequently encountered in criminal investigations but often overlooked as potential evidence. We designed a DNA-based molecular identification system for 100 Australian grasses that consisted of a series of polymerase chain reaction assays that enabled the progressive identification of grasses to different taxonomic levels. The identification system was based on DNA sequence variation at four chloroplast and two mitochondrial loci. Seventeen informative indels and 68 single-nucleotide polymorphisms were utilized as molecular markers for subfamily to species-level identification. To identify an unknown sample to subfamily level required a minimum of four markers or nine markers for species identification. The accuracy of the system was confirmed by blind tests. We have demonstrated "proof of concept" of a molecular identification system for trace botanical samples. Our evaluation suggests that the adoption of a system that combines this approach with DNA sequencing could assist the morphological identification of grasses found as forensic evidence.

Markers linked to vegetative incompatibility (vic) genes and a region of high heterogeneity and reduced recombination near the mating type locus (MAT) in Cryphonectria parasitica

Treesearch

Thomas L. Kubisiak; Michael g. Milgroom

2006-01-01

To find markers linked to vegetative incompatibility (vic) genes in the chestnut blight fungus, Cryphonectria parasitica, we constructed a preliminary linkage map. In general, this map is characterized by low levels of polymorphism, as evident from the more than 24 linkage groups observed, compared to seven expected from electrophoretic karyotyping....

An 'integrative neuroscience' perspective on ADHD: linking cognition, emotion, brain and genetic measures with implications for clinical support.

PubMed

Williams, Leanne M; Tsang, Tracey W; Clarke, Simon; Kohn, Michael

2010-10-01

There remains a translational gap between research findings and their implementation in clinical practice that applies to attention-deficit/hyperactivity disorder (ADHD), as well as to other major disorders of brain health in childhood, adolescence and adulthood. Research studies have identified potential 'markers' to support diagnostic, functional assessment and treatment decisions, but there is little consensus about these markers. Of these potential markers, cognitive measures of thinking functions, such as sustaining attention and associated electrical brain activity, show promise in complementing the clinical management process. Emerging evidence highlights the relevance of emotional, as well as thinking, functions to ADHD. Here, we outline an integrative neuroscience framework for ADHD that offers one means to bring together cognitive measures of thinking functions with measures of emotion, and their brain and genetic correlates. Understanding these measures and the relationships between them is a first step towards the development of tools that will help to assess the heterogeneity of ADHD, and aid in tailoring treatment choices.

Insight into the Migration Routes of Plutella xylostella in China Using mtCOI and ISSR Markers

PubMed Central

Tian, Lixia; Xu, Baoyun; Xie, Wen; Wang, Shaoli; Zhang, Youjun; Wang, Xiangjing; Wu, Qingjun

2015-01-01

The larvae of the diamondback moth, Plutella xylostella, cause major economic losses to cruciferous crops, including cabbage, which is an important vegetable crop in China. In this study, we used the mitochondrial COI gene and 11 ISSR markers to characterize the genetic structure and seasonal migration routes of 23 P. xylostella populations in China. Both the mitochondrial and nuclear markers revealed high haplotype diversity and gene flow among the populations, although some degree of genetic isolation was evident between the populations of Hainan Island and other sampling sites. The dominant haplotypes, LX1 and LX2, differed significantly from all other haplotypes both in terms of the number of individuals with those haplotypes and their distributions. Haplotypes that were shared among populations revealed that P. xylostella migrates from the lower reaches of the Yangtze River to northern China and then to northeastern China. Our results also revealed another potential migration route for P. xylostella, i.e., from southwestern China to both northwestern and southern China. PMID:26098353

Sublocalization of an Ataxia-Telangiectasia Gene Distal to D11S384 by Ancestral Haplotyping In Costa Rican Families

PubMed Central

Uhrhammer, Nancy; Lange, Ethan; Porras, Oscar; Naeim, Arash; Chen, Xiaoguang; Sheikhavandi, Sepideh; Chiplunkar, Sujata; Yang, Lan; Dandekar, Sugandha; Liang, Teresa; Patel, Nima; Teraoka, Sharon; Udar, Nitin; Calvo, Nidia; Concannon, Patrick; Lange, Kenneth; Gatti, Richard A.

1995-01-01

In an effort to localize a gene for ataxia-telangiectasia (A-T), we have genotyped 27 affected Costa Rican families, with 13 markers, in the chromosome 11q22-23 region. Significant linkage disequilibrium was detected for 9/13 markers between D11S1816 and D11S1391. Recombination events observed in these pedigrees places A-T between D11S1819 and D11S1960. One ancestral haplotype is common to 24/54 affected chromosomes and roughly two-thirds of the families. Inferred (ancestral) recombination events involving this common haplotype in earlier generations suggest that A-T is distal to D11S384 and proximal to D11S1960. Several other common haplotypes were identified, consistent with multiple mutations in a single gene. When considered together with all other evidence, this study further sublocalizes the major A-T locus to ≈200 kb, between markers S384 and S535. ImagesFigure 5 PMID:7611278

Interleukin-1β modulates smooth muscle cell phenotype to a distinct inflammatory state relative to PDGF-DD via NF-κB-dependent mechanisms.

PubMed

Alexander, Matthew R; Murgai, Meera; Moehle, Christopher W; Owens, Gary K

2012-04-02

Smooth muscle cell (SMC) phenotypic modulation in atherosclerosis and in response to PDGF in vitro involves repression of differentiation marker genes and increases in SMC proliferation, migration, and matrix synthesis. However, SMCs within atherosclerotic plaques can also express a number of proinflammatory genes, and in cultured SMCs the inflammatory cytokine IL-1β represses SMC marker gene expression and induces inflammatory gene expression. Studies herein tested the hypothesis that IL-1β modulates SMC phenotype to a distinct inflammatory state relative to PDGF-DD. Genome-wide gene expression analysis of IL-1β- or PDGF-DD-treated SMCs revealed that although both stimuli repressed SMC differentiation marker gene expression, IL-1β distinctly induced expression of proinflammatory genes, while PDGF-DD primarily induced genes involved in cell proliferation. Promoters of inflammatory genes distinctly induced by IL-1β exhibited over-representation of NF-κB binding sites, and NF-κB inhibition in SMCs reduced IL-1β-induced upregulation of proinflammatory genes as well as repression of SMC differentiation marker genes. Interestingly, PDGF-DD-induced SMC marker gene repression was not NF-κB dependent. Finally, immunofluorescent staining of mouse atherosclerotic lesions revealed the presence of cells positive for the marker of an IL-1β-stimulated inflammatory SMC, chemokine (C-C motif) ligand 20 (CCL20), but not the PDGF-DD-induced gene, regulator of G protein signaling 17 (RGS17). Results demonstrate that IL-1β- but not PDGF-DD-induced phenotypic modulation of SMC is characterized by NF-κB-dependent activation of proinflammatory genes, suggesting the existence of a distinct inflammatory SMC phenotype. In addition, studies provide evidence for the possible utility of CCL20 and RGS17 as markers of inflammatory and proliferative state SMCs within atherosclerotic plaques in vivo.

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).

Association of Inflammation With Loss Of Ability to Walk 400 Meters: Longitudinal Findings From the Inchianti Study

PubMed Central

Vasunilashorn, Sarinnapha; Ferrucci, Luigi; Crimmins, Eileen M.; Bandinelli, Stefania; Guralnik, Jack M.; Patel, Kushang V.

2013-01-01

Objectives To examine relationships between eight markers of inflammation (interleukin [IL]-6, IL-6 receptor [R], C-reactive protein [CRP], tumor necrosis factor [TNF]-α, TNF receptor 1[R1], TNFR2, IL-1 receptor antagonist, IL-18) and incident loss of ability to walk 400 m. Design Prospective cohort study. Setting Older adults enrolled in the InvecchiareInChianti Study. Participants One thousand six community-dwelling participants aged 65+. Measurements The eight inflammatory markers were measured at baseline, and an inflammation score was calculated based on the number of inflammatory markers for which the participant was in the highest quartile. Incidence of mobility disability was determined among participants able to walk 400 m at baseline. Logistic regression models were used to determine whether each of the inflammatory markers and the inflammation score predicts loss of the ability to walk 400 m at six-year follow-up. Results After adjusting for covariates, individuals with aTNFR1 level in each of the top 3 quartiles (Q2, 3, 4) were more likely to be unable to walk 400 m at follow-up compared to those with TNFR1 levels in Q1. When adjusting for the same covariates, participants with an inflammation score of 3 or 4 were more likely to become unable to complete the 400 m walk at follow-up compared to participants with a score of 0. Conclusion These results bring additional evidence to the notion that inflammation is implicated in the mechanisms that cause incident mobility disability and suggest that a combined measure of inflammatory markers may improve our prediction of functional prognosis. PMID:24083386

Association of inflammation with loss of ability to walk 400 meters: longitudinal findings from the Invecchiare in Chianti Study.

PubMed

Vasunilashorn, Sarinnapha; Ferrucci, Luigi; Crimmins, Eileen M; Bandinelli, Stefania; Guralnik, Jack M; Patel, Kushang V

2013-10-01

To examine relationships between eight markers of inflammation (interleukin (IL)-6, IL-6 receptor (R), C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha, TNF receptor 1 (R1), TNFR2, IL-1 receptor antagonist, IL-18) and incident loss of ability to walk 400 m. Prospective cohort study. Older adults enrolled in the Invecchiare in Chianti Study. Community-dwelling participants aged 65 and older (N = 1,006). The eight inflammatory markers were measured at baseline, and an inflammation score was calculated based on the number of inflammatory markers for which the participant was in the highest quartile. Incidence of mobility disability was determined in participants able to walk 400 m at baseline. Logistic regression models were used to determine whether each of the inflammatory markers and the inflammation score predicted loss of the ability to walk 400 m at 6-year follow-up. After adjusting for covariates, individuals with a TNFR1 level in each of the highest three quartiles (Q2, 3, 4) were more likely to be unable to walk 400 m at follow-up than those with TNFR1 levels in Q1. When adjusting for the same covariates, participants with an inflammation score of 3 or 4 were more likely to become unable to walk 400 m at follow-up than participants with a score of 0. These results provide additional evidence that inflammation is a factor in the mechanisms that cause incident mobility disability and suggest that a combined measure of inflammatory markers may improve prediction of functional prognosis. © 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.

Effect of IGF1, GH, and PIT1 markers on the genetic parameters of growth and reproduction traits in Canchim cattle.

PubMed

Grossi, Daniela do Amaral; Buzanskas, Marcos Eli; Grupioni, Natalia Vinhal; de Paz, Claudia Cristina Paro; Regitano, Luciana Correia de Almeida; de Alencar, Maurício Mello; Schenkel, Flávio Schramm; Munari, Danísio Prado

2015-01-01

The availability of dense genomic information has increased genome-wide association studies for the bovine species; however research to assess the effect of single genes on production traits is still important to elucidate the genes functions. On this study the association of IGF1, GH, and PIT1 markers with growth and reproductive traits (birth weight, weaning weight, weight at 12 and 18 months of age, preweaning average daily weight gain, age and weight at first calving, and scrotal circumference at 12 and 18 months of age) were assessed by means of the variance component approach. The phenotypes were adjusted and then analyzed under two animal models, one which considered the polygenic and genotype (IGF1, GH or PIT1 markers) effects (Model 1), and the other which considers only the polygenic effect (Model 2). When the likelihood ratio test and the Bonferroni correction was applied at 5 % significance level, the genetic markers for the IGF1, GH, and PIT1 genes did not influence significantly the traits (p > 0.002). However, evidence of association of IGF1 with birth weight (p = 0.06) and GH with weight at first calving (p = 0.03) and with weight at 12 months of age (p = 0.08) was observed. In conclusion we could not confirm the associations between IGF1, GH, and PIT1 and growth traits that were previously reported in Canchim cattle, and no association was observed between these genes and reproductive traits. Future studies involving functional markers of IGF1, GH and PIT1 genes may help to clarify the role of these genes in growth and reproductive processes.

Inflammatory Markers and Plasma Lipids in HIV Patients: A Correlation Analysis Study

PubMed Central

Muswe, Rudo; Oktedalen, Olav; Zhou, Danai T.; Zinyando, Enita; Shawarira-Bote, Sandra; Stray-Pedersen, Babill; Siziba, Atipa; Gomo, Zvenyika A.R.

2017-01-01

Background: Recent evidence suggests that HIV infection, even with treatment, increases the risk of coronary heart disease (CHD) and that both chronic inflammation and traditional risk factors play key roles in HIV-associated CHD. Subjects and Methods: Patients (N=152), attending Harare HIV clinic, 26% of them male and 82% of them on antiretroviral therapy (ART), were studied. Inflammatory markers comprising of cytokines such as pro-inflammatory tumor necrosis factor-α, (TNF-α), anti-inflammatory interleukin 10, (IL-10) and highly sensitive C reactive protein (hsCRP) together with lipids were assayed using enzyme linked immunosorbent assay (ELISA), immuno-turbidimetric and enzymatic assays, respectively. Correlation analysis of inflammatory markers versus lipid profiles was carried out using bivariate regression analysis. Results: Anti-inflammatory cytokine IL-10 and inflammatory hsCRP levels were elevated when measured in all the HIV positive patients, while TNF-α and lipid levels were within normal ranges. Pro-inflammatory TNF-α was significantly higher in ART-naive patients than ART-experienced patients, whereas the reverse was observed for anti-inflammatory IL-10 and anti-atherogenic HDL-C. Correlation analysis indicated a significant positive linear association between IL-10 and total cholesterol (TC) levels but no other correlations were found. Conclusion: High cytokine ratio (TNF-α/IL-10) indicates higher CHD risk in ART-naive patients compared to the ART-exposed. The CHD risk could be further strengthened by interplay between inflammatory markers and high prevalence of low HDL-C. Lack of correlation between pro-inflammatory markers (hsCRP and TNF-α) with lipid fractions and correlation between anti-inflammatory IL-10 with artherogenic TC were unexpected findings, necessitating further studies in future. PMID:29387269

Changes in markers of liver function in relation to changes in perfluoroalkyl substances - A longitudinal study.

PubMed

Salihovic, Samira; Stubleski, Jordan; Kärrman, Anna; Larsson, Anders; Fall, Tove; Lind, Lars; Lind, P Monica

2018-08-01

While it is known that perfluoroalkyl substances (PFASs) induce liver toxicity in experimental studies, the evidence of an association in humans is inconsistent. The main aim of the present study was to examine the association of PFAS concentrations and markers of liver function using panel data. We investigated 1002 individuals from Sweden (50% women) at ages 70, 75 and 80 in 2001-2014. Eight PFASs were measured in plasma using isotope dilution ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS). Bilirubin and hepatic enzymes alanine aminotransferase (ALT), alkaline phosphatase (ALP), and γ-glutamyltransferase (GGT) were determined in serum using an immunoassay methodology. Mixed-effects linear regression models were used to examine the relationship between the changes in markers of liver function and changes in PFAS levels. The changes in majority of PFAS concentrations were positively associated with the changes in activity of ALT, ALP, and GGT and inversely associated with the changes in circulating bilirubin after adjustment for gender and the time-updated covariates LDL- and HDL-cholesterol, serum triglycerides, BMI, statin use, smoking, fasting glucose levels and correction for multiple testing. For example, changes in perfluorononanoic acid (PFNA) were associated with the changes liver function markers β BILIRUBIN  = -1.56, 95% confidence interval (CI) -1.93 to -1.19, β ALT  = 0.04, 95% CI 0.03-0.06, and β ALP  = 0.11, 95% CI 0.06-0.15. Our longitudinal assessment established associations between changes in markers of liver function and changes in plasma PFAS concentrations. These findings suggest a relationship between low-dose background PFAS exposure and altered liver function in the general population. Copyright © 2018 Elsevier Ltd. All rights reserved.

Educational games for brain health: revealing their unexplored potential through a neurocognitive approach.

PubMed

Fissler, Patrick; Kolassa, Iris-Tatjana; Schrader, Claudia

2015-01-01

Educational games link the motivational nature of games with learning of knowledge and skills. Here, we go beyond effects on these learning outcomes. We review two lines of evidence which indicate the currently unexplored potential of educational games to promote brain health: First, gaming with specific neurocognitive demands (e.g., executive control), and second, educational learning experiences (e.g., studying foreign languages) improve brain health markers. These markers include cognitive ability, brain function, and brain structure. As educational games allow the combination of specific neurocognitive demands with educational learning experiences, they seem to be optimally suited for promoting brain health. We propose a neurocognitive approach to reveal this unexplored potential of educational games in future research.

Educational games for brain health: revealing their unexplored potential through a neurocognitive approach

PubMed Central

Fissler, Patrick; Kolassa, Iris-Tatjana; Schrader, Claudia

2015-01-01

Educational games link the motivational nature of games with learning of knowledge and skills. Here, we go beyond effects on these learning outcomes. We review two lines of evidence which indicate the currently unexplored potential of educational games to promote brain health: First, gaming with specific neurocognitive demands (e.g., executive control), and second, educational learning experiences (e.g., studying foreign languages) improve brain health markers. These markers include cognitive ability, brain function, and brain structure. As educational games allow the combination of specific neurocognitive demands with educational learning experiences, they seem to be optimally suited for promoting brain health. We propose a neurocognitive approach to reveal this unexplored potential of educational games in future research. PMID:26257697

Joint multi-population analysis for genetic linkage of bipolar disorder or "wellness" to chromosome 4p.

PubMed

Visscher, P M; Haley, C S; Ewald, H; Mors, O; Egeland, J; Thiel, B; Ginns, E; Muir, W; Blackwood, D H

2005-02-05

To test the hypothesis that the same genetic loci confer susceptibility to, or protection from, disease in different populations, and that a combined analysis would improve the map resolution of a common susceptibility locus, we analyzed data from three studies that had reported linkage to bipolar disorder in a small region on chromosome 4p. Data sets comprised phenotypic information and genetic marker data on Scottish, Danish, and USA extended pedigrees. Across the three data sets, 913 individuals appeared in the pedigrees, 462 were classified, either as unaffected (323) or affected (139) with unipolar or bipolar disorder. A consensus linkage map was created from 14 microsatellite markers in a 33 cM region. Phenotypic and genetic data were analyzed using a variance component (VC) and allele sharing method. All previously reported elevated test statistics in the region were confirmed with one or both analysis methods, indicating the presence of one or more susceptibility genes to bipolar disorder in the three populations in the studied chromosome segment. When the results from both the VC and allele sharing method were considered, there was strong evidence for a susceptibility locus in the data from Scotland, some evidence in the data from Denmark and relatively less evidence in the data from the USA. The test statistics from the Scottish data set dominated the test statistics from the other studies, and no improved map resolution for a putative genetic locus underlying susceptibility in all three studies was obtained. Studies reporting linkage to the same region require careful scrutiny and preferably joint or meta analysis on the same basis in order to ensure that the results are truly comparable. (c) 2004 Wiley-Liss, Inc.

Comparison of treatment effect sizes from pivotal and postapproval trials of novel therapeutics approved by the FDA based on surrogate markers of disease: a meta-epidemiological study.

PubMed

Wallach, Joshua D; Ciani, Oriana; Pease, Alison M; Gonsalves, Gregg S; Krumholz, Harlan M; Taylor, Rod S; Ross, Joseph S

2018-03-21

The U.S. Food and Drug Administration (FDA) often approves new drugs based on trials that use surrogate markers for endpoints, which involve certain trade-offs and may risk making erroneous inferences about the medical product's actual clinical effect. This study aims to compare the treatment effects among pivotal trials supporting FDA approval of novel therapeutics based on surrogate markers of disease with those observed among postapproval trials for the same indication. We searched Drugs@FDA and PubMed to identify published randomized superiority design pivotal trials for all novel drugs initially approved by the FDA between 2005 and 2012 based on surrogate markers as primary endpoints and published postapproval trials using the same surrogate markers or patient-relevant outcomes as endpoints. Summary ratio of odds ratios (RORs) and difference between standardized mean differences (dSMDs) were used to quantify the average difference in treatment effects between pivotal and matched postapproval trials. Between 2005 and 2012, the FDA approved 88 novel drugs for 90 indications based on one or multiple pivotal trials using surrogate markers of disease. Of these, 27 novel drugs for 27 indications were approved based on pivotal trials using surrogate markers as primary endpoints that could be matched to at least one postapproval trial, for a total of 43 matches. For nine (75.0%) of the 12 matches using the same non-continuous surrogate markers as trial endpoints, pivotal trials had larger treatment effects than postapproval trials. On average, treatment effects were 50% higher (more beneficial) in the pivotal than the postapproval trials (ROR 1.5; 95% confidence interval CI 1.01-2.23). For 17 (54.8%) of the 31 matches using the same continuous surrogate markers as trial endpoints, pivotal trials had larger treatment effects than the postapproval trials. On average, there was no difference in treatment effects between pivotal and postapproval trials (dSMDs 0.01; 95% CI -0.15-0.16). Many postapproval drug trials are not directly comparable to previously published pivotal trials, particularly with respect to endpoint selection. Although treatment effects from pivotal trials supporting FDA approval of novel therapeutics based on non-continuous surrogate markers of disease are often larger than those observed among postapproval trials using surrogate markers as trial endpoints, there is no evidence of difference between pivotal and postapproval trials using continuous surrogate markers.

Microsatellites for Oenothera gayleana and O. hartwegii subsp. filifolia (Onagraceae), and their utility in section Calylophus.

PubMed

Lewis, Emily M; Fant, Jeremie B; Moore, Michael J; Hastings, Amy P; Larson, Erica L; Agrawal, Anurag A; Skogen, Krissa A

2016-02-01

Eleven nuclear and four plastid microsatellite markers were screened for two gypsum endemic species, Oenothera gayleana and O. hartwegii subsp. filifolia, and tested for cross-amplification in the remaining 11 taxa within Oenothera sect. Calylophus (Onagraceae). Microsatellite markers were tested in two to three populations spanning the ranges of both O. gayleana and O. hartwegii subsp. filifolia. The nuclear microsatellite loci consisted of both di- and trinucleotide repeats with one to 17 alleles per population. Several loci showed significant deviation from Hardy-Weinberg equilibrium, which may be evidence of chromosomal rings. The plastid microsatellite markers identified one to seven haplotypes per population. The transferability of these markers was confirmed in all 11 taxa within Oenothera sect. Calylophus. The microsatellite loci characterized here are the first developed and tested in Oenothera sect. Calylophus. These markers will be used to assess whether pollinator foraging distance influences population genetic parameters in predictable ways.

Evidence of cryptic introgression in tomato (Solanum lycopersicum L.) based on wild tomato species alleles.

PubMed

Labate, Joanne A; Robertson, Larry D

2012-08-07

Many highly beneficial traits (e.g. disease or abiotic stress resistance) have been transferred into crops through crosses with their wild relatives. The 13 recognized species of tomato (Solanum section Lycopersicon) are closely related to each other and wild species genes have been extensively used for improvement of the crop, Solanum lycopersicum L. In addition, the lack of geographical barriers has permitted natural hybridization between S. lycopersicum and its closest wild relative Solanum pimpinellifolium in Ecuador, Peru and northern Chile. In order to better understand patterns of S. lycopersicum diversity, we sequenced 47 markers ranging in length from 130 to 1200 bp (total of 24 kb) in genotypes of S. lycopersicum and wild tomato species S. pimpinellifolium, Solanum arcanum, Solanum peruvianum, Solanum pennellii and Solanum habrochaites. Between six and twelve genotypes were comparatively analyzed per marker. Several of the markers had previously been hypothesized as carrying wild species alleles within S. lycopersicum, i.e., cryptic introgressions. Each marker was mapped with high confidence (e<1 x 10-30) to a single genomic location using BLASTN against tomato whole genome shotgun chromosomes (SL2.40) database. Neighbor-joining trees showed high mean bootstrap support (86.8 ± 2.34%) for distinguishing red-fruited from green-fruited taxa for 38 of the markers. Hybridization and parsimony splits networks, genomic map positions of markers relative to documented introgressions, and historical origins of accessions were used to interpret evolutionary patterns at nine markers with putatively introgressed alleles. Of the 47 genetic markers surveyed in this study, four were involved in linkage drag on chromosome 9 during introgression breeding, while alleles at five markers apparently originated from natural hybridization with S. pimpinellifolium and were associated with primitive genotypes of S. lycopersicum. The positive identification of introgressed genes within crop species such as S. lycopersicum will help inform conservation and utilization of crop germplasm diversity, for example, facilitating the purging of undesirable linkage drag or the exploitation of novel, favorable alleles.

Role of Microglia Disturbances and Immune-Related Marker Abnormalities in Cortical Circuitry Dysfunction in Schizophrenia

PubMed Central

Volk, David W.

2017-01-01

Studies of genetics, serum cytokines, and autoimmune illnesses suggest that immune-related abnormalities are involved in the disease process of schizophrenia. Furthermore, direct evidence of cortical immune activation, including markedly elevated levels of many immune-related markers, have been reported in the prefrontal cortex in multiple cohorts of schizophrenia subjects. Within the prefrontal cortex in schizophrenia, deficits in the basilar dendritic spines of layer 3 pyramidal neurons and disturbances in inhibitory inputs to pyramidal neurons have also been commonly reported. Interestingly, microglia, the resident immune-related cells of the brain, also regulate excitatory and inhibitory input to pyramidal neurons. Consequently, in this review, we describe the cytological and molecular evidence of immune activation that has been reported in the brains of individuals with schizophrenia and the potential links between these immune-related disturbances with previously reported disturbances in pyramidal and inhibitory neurons in the disorder. Finally, we discuss the role that activated microglia may play in connecting these observations and as potential therapeutic treatment targets in schizophrenia. PMID:28007586

The EEG as an index of neuromodulator balance in memory and mental illness.

PubMed

Vakalopoulos, Costa

2014-01-01

There is a strong correlation between signature EEG frequency patterns and the relative levels of distinct neuromodulators. These associations become particularly evident during the sleep-wake cycle. The monoamine-acetylcholine balance hypothesis is a theory of neurophysiological markers of the EEG and a detailed description of the findings that support this proposal are presented in this paper. According to this model alpha rhythm reflects the relative predominance of cholinergic muscarinic signals and delta rhythm that of monoaminergic receptor effects. Both high voltage synchronized rhythms are likely mediated by inhibitory Gαi/o-mediated transduction of inhibitory interneurons. Cognitively, alpha and delta EEG measures are proposed to indicate automatic and flexible strategies, respectively. Sleep is associated with marked changes in relative neuromodulator levels corresponding to EEG markers of distinct stages. Sleep studies on memory consolidation present some of the strongest evidence yet for the respective roles of monoaminergic and cholinergic projections in declarative and non-declarative memory processes, a key theoretical premise for understanding the data. Affective dysregulation is reflected in altered EEG patterns during sleep.

Further evidence of an Amerindian contribution to the Polynesian gene pool on Easter Island.

PubMed

Thorsby, E; Flåm, S T; Woldseth, B; Dupuy, B M; Sanchez-Mazas, A; Fernandez-Vina, M A

2009-06-01

Available evidence suggests a Polynesian origin of the Easter Island population. We recently found that some native Easter Islanders also carried some common American Indian (Amerindian) human leukocyte antigen (HLA) alleles, which probably were introduced before Europeans discovered the island in 1722. In this study, we report molecular genetic investigations of 21 other selected native Easter Islanders. Analysis of mitochondrial DNA and Y chromosome markers showed no traces of an Amerindian contribution. However, high-resolution genomic HLA typing showed that two individuals carried some other common Amerindian HLA alleles, different from those found in our previous investigations. The new data support our previous evidence of an Amerindian contribution to the gene pool on Easter Island.

Cancer stem cells (CSCs), cervical CSCs and targeted therapies.

PubMed

Huang, Ruixia; Rofstad, Einar K

2017-05-23

Accumulating evidence has shown that cancer stem cells (CSCs) have a tumour-initiating capacity and play crucial roles in tumour metastasis, relapse and chemo/radio-resistance. As tumour propagation initiators, CSCs are considered to be promising targets for obtaining a better therapeutic outcome. Cervical carcinoma is the most common gynaecological malignancy and has a high cancer mortality rate among females. As a result, the investigation of cervical cancer stem cells (CCSCs) is of great value. However, the numbers of cancer cells and corresponding CSCs in malignancy are dynamically balanced, and CSCs may reside in the CSC niche, about which little is known to date. Therefore, due to their complicated molecular phenotypes and biological behaviours, it remains challenging to obtain "purified" CSCs and continuously culture CSCs for further in vitro studies without the cells losing their stem properties. At present, CSC-related markers and functional assays are used to purify, identify and therapeutically target CSCs both in vitro and in vivo. Nevertheless, CSC-related markers are not universal to all tumour types, although some markers may be valid in multiple tumour types. Additionally, functional identifications based on CSC-specific properties are usually limited in in vivo studies. Furthermore, an optimal method for identifying potential CCSCs in CCSC studies has not been previously published, and these techniques are currently of great importance. This article updates our knowledge on CSCs and CCSCs, reviews potential stem cell markers and functional assays for identifying CCSCs, and describes the potential of targeting CCSCs in the treatment of cervical carcinoma.

Grammar Clinical Marker Yields Substantial Heritability for Language Impairments in 16-Year-Old Twins.

PubMed

Dale, Philip S; Rice, Mabel L; Rimfeld, Kaili; Hayiou-Thomas, Marianna E

2018-01-22

There is a need for well-defined language phenotypes suitable for adolescents in twin studies and other large-scale research projects. Rice, Hoffman, and Wexler (2009) have developed a grammatical judgment measure as a clinical marker of language impairment, which has an extended developmental range to adolescence. We conducted the first twin analysis, along with associated phenotypic analyses of validity, of an abridged, 20-item version of this grammatical judgment measure (GJ-20), based on telephone administration using prerecorded stimuli to 405 pairs of 16-year-olds (148 monozygotic and 257 dizygotic) drawn from the Twins Early Development Study (Haworth, Davis, & Plomin, 2012). The distribution of scores is markedly skewed negatively, as expected for a potential clinical marker. Low performance on GJ-20 is associated with lower maternal education, reported learning disability (age 7 years), and low scores on language tests administered via the Twins Early Development Study (age 16 years) as well as General Certificate of Secondary Education English and Math examination performance (age 16 years). Liability threshold estimates for the genetic influence on low performance on GJ-20 are substantial, ranging from 36% with a lowest 10% criterion to 74% for a lowest 5% criterion. The heritability of GJ-20 scores, especially at more extreme cutoffs, along with the score distribution and association with other indicators of language impairments, provides additional evidence for the potential value of this measure as a clinical marker of specific language impairment.

Background frequency of Bacillus species at the Canberra Airport: A 12 month study.

PubMed

Gahan, Michelle E; Thomas, Rory; Rossi, Rebecca; Nelson, Michelle; Roffey, Paul; Richardson, Michelle M; McNevin, Dennis

2015-12-01

Anthrax, caused by Bacillus anthracis, is a naturally occurring disease in Australia. Whilst mainly limited to livestock in grazing regions of Victoria and New South Wales, movement of people, stock and vehicles means B. anthracis could be present outside this region. Of particular interest is the "background" prevalence of B. anthracis at transport hubs including airports. The aim of this study was to determine the background frequency of B. anthracis and the commonly used hoax agent Bacillus thuringiensis at the Canberra Airport over a 12 month period. Samples were collected daily for seven days each month from August 2011-July 2012 and analyzed using species specific real-time polymerase chain reaction. Fourteen samples (of a total of 575) were positive for the B. anthracis PL3 genomic marker, 24 for the cya (pXO1) plasmid marker and five for the capB (pXO2) plasmid marker. Whilst five samples were positive for both PL3 and cya, no samples were positive for all three markers hence there is no evidence to suggest the presence of pathogenic B. anthracis strains. B. anthracis targets were detected primarily in February 2012 and B. thuringiensis peaked in October and November 2011 and again in April and May 2012. This study provides a rapid method to screen for, and differentiate, Bacillus species. Armed with this information investigators will be able to discriminate a "threat" from "background" frequencies should the need arise. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Molecular mechanisms underlying the antitumor activity of (E)-N-hydroxy-3-(1-(4-methoxyphenylsulfonyl)-1,2,3,4-tetrahydroquinolin-6-yl)acrylamide in human colorectal cancer cells in vitro and in vivo

PubMed Central

Chen, Chun-Han; Lee, Chia-Hwa; Liou, Jing-Ping; Teng, Che-Ming; Pan, Shiow-Lin

2015-01-01

Upregulation of class I histone deacetylases (HDAC) correlates with poor prognosis in colorectal cancer (CRC) patients. Previous study revealed that (E)-N-hydroxy-3-(1-(4-methoxyphenylsulfonyl)-1,2,3,4-tetrahydroquinolin-6-yl)acrylamide (Compound 11) is a potent and selective class I HDAC inhibitor, exhibited significant anti-proliferative activity in various human cancer cell lines. In current study, we demonstrated that compound 11 exhibited significant anti-proliferative and cytotoxic activity in CRC cells. Notably, compound 11 was less potent than SAHA in inhibiting HDAC6 as evident from the lower expression of acetyl-α-tubulin, suggesting higher selectivity for class I HDACs. Mechanistically, compound 11 induced cell-cycle arrest at the G2/M phase, activated both intrinsic- and extrinsic-apoptotic pathways, altered the expression of Bcl-2 family proteins and exerted a potent inhibitory effect on survival signals (p-Akt, p-ERK) in CRC cells. Moreover, we provide evidence that compound 11 suppressed motility, decreased mesenchymal markers (N-cadherin and vimentin) and increased epithelial marker (E-cadherin) through down-regulation of Akt. The anti-tumor activity and underlying molecular mechanisms of compound 11 were further confirmed using the HCT116 xenograft model in vivo. Our findings provide evidence of the significant anti-tumor activity of compound 11 in a preclinical model, supporting its potential as a novel therapeutic agent for CRC. PMID:26462017

Ulex Europaeus Agglutinin-1 Is a Reliable Taste Bud Marker for In Situ Hybridization Analyses.

PubMed

Yoshimoto, Joto; Okada, Shinji; Kishi, Mikiya; Misaka, Takumi

2016-03-01

Taste signals are received by taste buds. To better understand the taste reception system, expression patterns of taste-related molecules are determined by in situ hybridization (ISH) analyses at the histological level. Nevertheless, even though ISH is essential for determining mRNA expression, few taste bud markers can be applied together with ISH. Ulex europaeus agglutinin-1 (UEA-1) appears to be a reliable murine taste bud marker based on immunohistochemistry (IHC) analyses. However, there is no evidence as to whether UEA-1 can be used for ISH. Thus, the present study evaluated UEA-1 using various histochemical methods, especially ISH. When lectin staining was performed after ISH procedures, UEA-1 clearly labeled taste cellular membranes and distinctly indicated boundaries between taste buds and the surrounding epithelial cells. Additionally, UEA-1 was determined as a taste bud marker not only when used in single-colored ISH but also when employed with double-labeled ISH or during simultaneous detection using IHC and ISH methods. These results suggest that UEA-1 is a useful marker when conducting analyses based on ISH methods. To clarify UEA-1 staining details, multi-fluorescent IHC (together with UEA-1 staining) was examined, resulting in more than 99% of cells being labeled by UEA-1 and overlapping with KCNQ1-expressing cells. © 2016 The Histochemical Society.

Exploring Geochemical Markers of the Anthropocene in River Sediments: Southern New England

NASA Astrophysics Data System (ADS)

Tran, J.

2015-12-01

The sedimentary record of New England is complex. From glacial till to colonial land use to the industrial revolution, any sediment preserved is intertwined and muddled by humans. Recent studies support the idea that any anthropogenic markers in the sediment record are site specific. Southern New England is marked by a myriad of practices including farming, charcoal kilns, hatting, mill dams, and iron furnaces. While specific markers of the anthropocene have been identified, little work has been done to correlate and quantify these noted markers across multiple basins. Specifically, a combination of x-ray fluorescence (XRF), x-ray diffraction (XRD), and grain size analysis were done on sediment cores taken within Southern New England across various watersheds. We present a combination of geochemical analysis and detrital zircon geochronology in order identify and account for basin differences. This in turn results in a more comprehensive trans-basin understanding of the anthropocene in this region. We observe strong evidence that supports the idea of geochemical markers anthropocene which include an increase in Mercury and Lead content in the sediments. Additionally, in basins where mill dams are present we observe sediment records consistent with flood events and dam degradation. While still fairly novel and understudied, our results provide insight to the much often question topic of the anthropocene in relation to this particular region and the potential pitfalls of doing large scale anthropogenic dating.

Ulex Europaeus Agglutinin-1 Is a Reliable Taste Bud Marker for In Situ Hybridization Analyses

PubMed Central

Yoshimoto, Joto; Okada, Shinji; Kishi, Mikiya; Misaka, Takumi

2015-01-01

Taste signals are received by taste buds. To better understand the taste reception system, expression patterns of taste-related molecules are determined by in situ hybridization (ISH) analyses at the histological level. Nevertheless, even though ISH is essential for determining mRNA expression, few taste bud markers can be applied together with ISH. Ulex europaeus agglutinin-1 (UEA-1) appears to be a reliable murine taste bud marker based on immunohistochemistry (IHC) analyses. However, there is no evidence as to whether UEA-1 can be used for ISH. Thus, the present study evaluated UEA-1 using various histochemical methods, especially ISH. When lectin staining was performed after ISH procedures, UEA-1 clearly labeled taste cellular membranes and distinctly indicated boundaries between taste buds and the surrounding epithelial cells. Additionally, UEA-1 was determined as a taste bud marker not only when used in single-colored ISH but also when employed with double-labeled ISH or during simultaneous detection using IHC and ISH methods. These results suggest that UEA-1 is a useful marker when conducting analyses based on ISH methods. To clarify UEA-1 staining details, multi-fluorescent IHC (together with UEA-1 staining) was examined, resulting in more than 99% of cells being labeled by UEA-1 and overlapping with KCNQ1-expressing cells. PMID:26718243

Is the relationship between sedentary behaviour and cardiometabolic health in adolescents independent of dietary intake? A systematic review.

PubMed

Fletcher, E; Leech, R; McNaughton, S A; Dunstan, D W; Lacy, K E; Salmon, J

2015-09-01

Screen time, but not overall sedentary behaviour, is consistently related to cardiometabolic health in adolescents. Because of the associations screen time has with dietary intake, diet may be an important factor in the screen time and health relationship; however, evidence has not previously been synthesized. Thus, the aim of this systematic review was to explore whether the associations between various sedentary behaviours and cardiometabolic risk markers are independent of dietary intake in adolescents. Online databases and personal libraries were searched for peer-reviewed original research articles published in English before March 2014. Included studies assessed associations between sedentary behaviour and cardiometabolic markers in 12- to 18-year-olds and adjusted for dietary intake. Twenty-five studies met the inclusion criteria. From the 21 studies examining sedentary behaviour and adiposity, the majority found significant positive associations between television viewing, screen time and self-reported overall sedentary behaviour with markers of adiposity, independent of dietary intake. No significant associations between screen time with blood pressure and cholesterol were reported. Sedentary behaviour appears to be associated with adiposity in adolescents, irrespective of dietary intake. However, the variability of dietary variables between studies suggests further work is needed to understand the role of dietary intake when examining these associations in youth. © 2015 World Obesity.

Potential Genetic Risk Factors for Chronic TMD: Genetic Associations from the OPPERA Case Control Study

PubMed Central

Smith, Shad B.; Maixner, Dylan; Greenspan, Joel; Dubner, Ron; Fillingim, Roger; Ohrbach, Richard; Knott, Charles; Slade, Gary; Bair, Eric; Gibson, Dustin G.; Zaykin, Dmitri V.; Weir, Bruce; Maixner, William; Diatchenko, Luda

2011-01-01

Genetic factors play a role in the etiology of persistent pain conditions, putatively by modulating underlying processes such as nociceptive sensitivity, psychological well-being, inflammation, and autonomic response. However, to date, only a few genes have been associated with temporomandibular disorders (TMD). This study evaluated 358 genes involved in pain processes, comparing allelic frequencies between 166 cases with chronic TMD and 1442 controls enrolled in the OPPERA (Orofacial Pain: Prospective Evaluation and Risk Assessment) study cooperative agreement. To enhance statistical power, 182 TMD cases and 170 controls from a similar study were included in the analysis. Genotyping was performed using the Pain Research Panel, an Affymetrix gene chip representing 3295 single nucleotide polymorphisms, including ancestry-informative markers that were used to adjust for population stratification. Adjusted associations between genetic markers and TMD case status were evaluated using logistic regression. The OPPERA findings provided evidence supporting previously-reported associations between TMD and two genes: HTR2A and COMT. Other genes were revealed as potential new genetic risk factors for TMD, including NR3C1, CAMK4, CHRM2, IFRD1, and GRK5. While these findings need to be replicated in independent cohorts, the genes potentially represent important markers of risk for TMD and they identify potential targets for therapeutic intervention. PMID:22074755

Tourette's Disorder: Genetic Update, Neurological Correlates, and Evidence-Based Interventions

ERIC Educational Resources Information Center

Phelps, LeAdelle

2008-01-01

This article provides an update of the search for genetic markers related to Tourette's Disorder. The probable neurophysiology of the disorder is reviewed. Frequently prescribed medications are related to the probable biological bases of the disorder. Behavioral interventions and assessment tools are examined. It is concluded that evidence based…

Preliminary evidence for associations between molecular markers and quantitative traits in a set of bread wheat (Triticum aestivum L.) cultivars and breeding lines.

PubMed

Abdollahi Mandoulakani, Babak; Nasri, Shilan; Dashchi, Sahar; Arzhang, Sorour; Bernousi, Iraj; Abbasi Holasou, Hossein

The identification of polymorphic markers associated with various quantitative traits allows us to test their performance for the exploitation of the extensive quantitative variation maintained in gene banks. In the current study, a set of 97 wheat germplasm accessions including 48 cultivars and 49 breeding lines were evaluated for 18 agronomic traits. The accessions were also genotyped with 23 ISSR, nine IRAP and 20 REMAP markers, generating a total of 658 clear and scorable bands, 86% of which were polymorphic. Both neighbor-joining dendrogram and Bayesian analysis of clustering of individuals revealed that the accessions could be divided into four genetically distinct groups, indicating the presence of a population structure in current wheat germplasm. Associations between molecular markers and 18 agronomic traits were analyzed using the mixed linear model (MLM) approach. A total of 94 loci were found to be significantly associated with agronomic traits (P≤0.01). The highest number of bands significantly associated with the 18 traits varied from 11 for number of spikelets spike -1 (NSS) to two for grain yield in row (GRY). Loci ISSR16-9 and REMAP13-10 were associated with three different traits. The results of the current study provide useful information about the performance of retrotransposon-based and ISSR molecular markers that could be helpful in selecting potentially elite gene bank samples for wheat-breeding programs. Copyright © 2017 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

Improving AFLP analysis of large-scale patterns of genetic variation--a case study with the Central African lianas Haumania spp (Marantaceae) showing interspecific gene flow.

PubMed

Ley, A C; Hardy, O J

2013-04-01

AFLP markers are often used to study patterns of population genetic variation and gene flow because they offer a good coverage of the nuclear genome, but the reliability of AFLP scoring is critical. To assess interspecific gene flow in two African rainforest liana species (Haumania danckelmaniana, H. liebrechtsiana) where previous evidence of chloroplast captures questioned the importance of hybridization and species boundaries, we developed new AFLP markers and a novel approach to select reliable bands from their degree of reproducibility. The latter is based on the estimation of the broad-sense heritability of AFLP phenotypes, an improvement over classical scoring error rates, which showed that the polymorphism of most AFLP bands was affected by a substantial nongenetic component. Therefore, using a quantitative genetics framework, we also modified an existing estimator of pairwise kinship coefficient between individuals correcting for the limited heritability of markers. Bayesian clustering confirms the recognition of the two Haumania species. Nevertheless, the decay of the relatedness between individuals of distinct species with geographic distance demonstrates that hybridization affects the nuclear genome. In conclusion, although we showed that AFLP markers might be substantially affected by nongenetic factors, their analysis using the new methods developed considerably advanced our understanding of the pattern of gene flow in our model species. © 2013 Blackwell Publishing Ltd.

Correlations between Blood–Brain Barrier Disruption and Neuroinflammation in an Experimental Model of Penetrating Ballistic-Like Brain Injury

PubMed Central

Cartagena, Casandra M.; Lu, Xi-Chun M.; Konopko, Melissa; Dave, Jitendra R.; Tortella, Frank C.; Shear, Deborah A.

2014-01-01

Abstract Blood–brain barrier (BBB) disruption is a pathological hallmark of severe traumatic brain injury (TBI) and is associated with neuroinflammatory events contributing to brain edema and cell death. The goal of this study was to elucidate the profile of BBB disruption after penetrating ballistic-like brain injury (PBBI) in conjunction with changes in neuroinflammatory markers. Brain uptake of biotin-dextran amine (BDA; 3 kDa) and horseradish peroxidase (HRP; 44 kDa) was evaluated in rats at 4 h, 24 h, 48 h, 72 h, and 7 days post-PBBI and compared with the histopathologic and molecular profiles for inflammatory markers. BDA and HRP both displayed a uniphasic profile of extravasation, greatest at 24 h post-injury and which remained evident out to 48 h for HRP and 7 days for BDA. This profile was most closely associated with markers for adhesion (mRNA for intercellular adhesion molecule-1) and infiltration of peripheral granulocytes (mRNA for matrix metalloproteinase-9 [MMP-9] and myeloperoxidase staining). Improvement of BBB dysfunction coincided with increased expression of markers implicated in tissue remodeling and repair. The results of this study reveal a uniphasic and gradient opening of the BBB after PBBI and suggest MMP-9 and resident inflammatory cell activation as candidates for future neurotherapeutic intervention after PBBI. PMID:24138024

Ursolic acid supplementation decreases markers of skeletal muscle damage during resistance training in resistance-trained men: a pilot study

PubMed Central

Bang, Hyun Seok; Seo, Dae Yun; Chung, Young Min; Kim, Do Hyung; Lee, Sam-Jun; Lee, Sung Ryul; Kwak, Hyo-Bum; Kim, Tae Nyun; Kim, Min; Oh, Kyoung-Mo; Son, Young Jin; Kim, Sanghyun

2017-01-01

Ursolic acid (UA) supplementation was previously shown to improve skeletal muscle function in resistance-trained men. This study aimed to determine, using the same experimental paradigm, whether UA also has beneficial effects on exercise-induced skeletal muscle damage markers including the levels of cortisol, B-type natriuretic peptide (BNP), myoglobin, creatine kinase (CK), creatine kinase-myocardial band (CK-MB), and lactate dehydrogenase (LDH) in resistance-trained men. Sixteen healthy participants were randomly assigned to resistance training (RT) or RT+UA groups (n=8 per group). Participants were trained according to the RT program (60~80% of 1 repetition, 6 times/week), and the UA group was additionally given UA supplementation (450 mg/day) for 8 weeks. Blood samples were obtained before and after intervention, and cortisol, BNP, myoglobin, CK, CK-MB, and LDH levels were analyzed. Subjects who underwent RT alone showed no significant change in body composition and markers of skeletal muscle damage, whereas RT+UA group showed slightly decreased body weight and body fat percentage and slightly increased lean body mass, but without statistical significance. In addition, UA supplementation significantly decreased the BNP, CK, CK-MB, and LDH levels (p<0.05). In conclusion, UA supplementation alleviates increased skeletal muscle damage markers after RT. This finding provides evidence for a potential new therapy for resistance-trained men. PMID:29200908

Effects of protein supplements on muscle damage, soreness and recovery of muscle function and physical performance: a systematic review.

PubMed

Pasiakos, Stefan M; Lieberman, Harris R; McLellan, Tom M

2014-05-01

Protein supplements are frequently consumed by athletes and recreationally-active individuals, although the decision to purchase and consume protein supplements is often based on marketing claims rather than evidence-based research. To provide a systematic and comprehensive analysis of literature examining the hypothesis that protein supplements enhance recovery of muscle function and physical performance by attenuating muscle damage and soreness following a previous bout of exercise. English language articles were searched with PubMed and Google Scholar using protein and supplements together with performance, exercise, competition and muscle, alone or in combination as keywords. Inclusion criteria required studies to recruit healthy adults less than 50 years of age and to evaluate the effects of protein supplements alone or in combination with carbohydrate on performance metrics including time-to-exhaustion, time-trial or isometric or isokinetic muscle strength and markers of muscle damage and soreness. Twenty-seven articles were identified of which 18 dealt exclusively with ingestion of protein supplements to reduce muscle damage and soreness and improve recovery of muscle function following exercise, whereas the remaining 9 articles assessed muscle damage as well as performance metrics during single or repeat bouts of exercise. Papers were evaluated based on experimental design and examined for confounders that explain discrepancies between studies such as dietary control, training state of participants, sample size, direct or surrogate measures of muscle damage, and sensitivity of the performance metric. High quality and consistent data demonstrated there is no apparent relationship between recovery of muscle function and ratings of muscle soreness and surrogate markers of muscle damage when protein supplements are consumed prior to, during or after a bout of endurance or resistance exercise. There also appears to be insufficient experimental data demonstrating ingestion of a protein supplement following a bout of exercise attenuates muscle soreness and/or lowers markers of muscle damage. However, beneficial effects such as reduced muscle soreness and markers of muscle damage become more evident when supplemental protein is consumed after daily training sessions. Furthermore, the data suggest potential ergogenic effects associated with protein supplementation are greatest if participants are in negative nitrogen and/or energy balance. Small sample numbers and lack of dietary control limited the effectiveness of several investigations. In addition, studies did not measure the effects of protein supplementation on direct indices of muscle damage such as myofibrillar disruption and various measures of protein signaling indicative of a change in rates of protein synthesis and degradation. As a result, the interpretation of the data was often limited. Overwhelmingly, studies have consistently demonstrated the acute benefits of protein supplementation on post-exercise muscle anabolism, which, in theory, may facilitate the recovery of muscle function and performance. However, to date, when protein supplements are provided, acute changes in post-exercise protein synthesis and anabolic intracellular signaling have not resulted in measureable reductions in muscle damage and enhanced recovery of muscle function. Limitations in study designs together with the large variability in surrogate markers of muscle damage reduced the strength of the evidence-base.

Exposure to human-associated fecal indicators and self-reported illness among swimmers at recreational beaches: a cohort study.

PubMed

Napier, Melanie D; Haugland, Richard; Poole, Charles; Dufour, Alfred P; Stewart, Jill R; Weber, David J; Varma, Manju; Lavender, Jennifer S; Wade, Timothy J

2017-10-02

Fecal indicator bacteria used to assess illness risks in recreational waters (e.g., Escherichia coli, Enterococci) cannot discriminate among pollution sources. To address this limitation, human-associated Bacteroides markers have been proposed, but the risk of illness associated with the presence of these markers in recreational waters is unclear. Our objective was to estimate associations between human-associated Bacteroides markers in water and self-reported illness among swimmers at 6 U.S. beaches spanning 2003-2007. We used data from a prospectively-enrolled cohort of 12,060 swimmers surveyed about beach activities and water exposure on the day of their beach visit. Ten to twelve days later, participants reported gastroinestinal, diarrheal, and respiratory illnesses experienced since the visit. Daily water samples were analyzed for the presence of human-associated Bacteroides genetic markers: HF183, BsteriF1, BuniF2, HumM2. We used model-based standardization to estimate risk differences (RD) and 95% confidence intervals (CI). We assessed whether the presence of Bacteroides markers were modifiers of the association between general Enterococcus and illness among swimmers using interaction contrast. Overall we observed inconsistent associations between the presence of Bacteroides markers and illness. There was a pattern of increased risks of gastrointestinal (RD = 1.9%; 95% CI: 0.1%, 3.7%), diarrheal (RD = 1.3%; 95% CI: -0.2%, 2.7%), and respiratory illnesses (RD = 1.1%; 95% CI: -0.2%, 2.5%) associated with BsteriF1. There was no evidence that Bacteroides markers acted as modifiers of Enterococcus and illness. Patterns were similar when stratified by water matrix. Quantitative measures of fecal pollution using Bacteroides, rather than presence-absence indicators, may be necessary to accurately assess human risk specific to the presence of human fecal pollution.

Disparities in child mortality trends: what is the evidence from disadvantaged states in India? the case of Orissa and Madhya Pradesh.

PubMed

Nguyen, Kim-Huong; Jimenez-Soto, Eliana; Dayal, Prarthna; Hodge, Andrew

2013-06-27

The Millennium Development Goals prompted renewed international efforts to reduce under-five mortality and measure national progress. However, scant evidence exists about the distribution of child mortality at low sub-national levels, which in diverse and decentralized countries like India are required to inform policy-making. This study estimates changes in child mortality across a range of markers of inequalities in Orissa and Madhya Pradesh, two of India's largest, poorest, and most disadvantaged states. Estimates of under-five and neonatal mortality rates were computed using seven datasets from three available sources--sample registration system, summary birth histories in surveys, and complete birth histories. Inequalities were gauged by comparison of mortality rates within four sub-state populations defined by the following characteristics: rural-urban location, ethnicity, wealth, and district. Trend estimates suggest that progress has been made in mortality rates at the state levels. However, reduction rates have been modest, particularly for neonatal mortality. Different mortality rates are observed across all the equity markers, although there is a pattern of convergence between rural and urban areas, largely due to inadequate progress in urban settings. Inter-district disparities and differences between socioeconomic groups are also evident. Although child mortality rates continue to decline at the national level, our evidence shows that considerable disparities persist. While progress in reducing under-five and neonatal mortality rates in urban areas appears to be levelling off, policies targeting rural populations and scheduled caste and tribe groups appear to have achieved some success in reducing mortality differentials. The results of this study thus add weight to recent government initiatives targeting these groups. Equitable progress, particularly for neonatal mortality, requires continuing efforts to strengthen health systems and overcome barriers to identify and reach vulnerable groups.

Initial report of a hepatitis investigation in rural Belize.

PubMed

Hoffman, K J; Gaydos, J C; Krieg, R E; Duncan, J F; MacArthy, P O; Ticehurst, J R; Jaramillo, R; Reyes, L G; Sjogren, M H; Legters, L J

1993-01-01

In spring 1991, Belizian health officials expressed concern about a possible hepatitis outbreak in a banana farming district. A study was designed to identify cases and to address the serological prevalence of hepatitis virus markers. Three populations were studied: (i) persons meeting a clinical case definition for hepatitis; (ii) designated banana workers; and (iii) people in a random sample of households in the community. Information was collected using questionnaires and sera were collected for laboratory testing. This report presents the preliminary results of a study conducted in June 1991. Among people who met the clinical case definition, 24% of 42 tested had immunoglobulin M antibody to hepatitis B virus (HBV) core antigen (anti-HBc IgM). In the worker and household survey populations, 284 and 280 people, respectively, were tested for anti-HBc IgM. In each group, 4% were positive. HBV surface antigen was found in 37% of 43 clinical cases, 18% of workers, and 13% of people in the household survey. Among the 3 study populations, the prevalence of HBV core antibody (anti-HBc) ranged from 73% to 81%. Almost all tested persons had evidence of prior hepatitis A virus infection. Evidence of prior infection with hepatitis viruses A and B was widespread, but an aetiology could not be established for most of the clinical cases. However, the prevalence of hepatitis B markers in this population was very high compared to other reports from the Caribbean.

Evidence for landscape-level, pollen-mediated gene flow from genetically modified creeping bentgrass with CP4 EPSPS as a marker

USGS Publications Warehouse

Watrud, L.S.; Lee, E.H.; Fairbrother, A.; Burdick, C.; Reichman, J.R.; Bollman, M.; Storm, M.; King, G.; Van De Water, Peter K.

2004-01-01

Sampling methods and results of a gene flow study are described that will be of interest to plant scientists, evolutionary biologists, ecologists, and stakeholders assessing the environmental safety of transgenic crops. This study documents gene flow on a landscape level from creeping bentgrass (Agrostis stolonifera L.), one of the first wind-pollinated, perennial, and highly outcrossing transgenic crops being developed for commercial use. Most of the gene flow occurred within 2 km in the direction of prevailing winds. The maximal gene flow distances observed were 21 km and 14 km in sentinel and resident plants, respectively, that were located in primarily nonagronomic habitats. The selectable marker used in these studies was the CP4 EPSPS gene derived from Agrobacterium spp. strain CP4 that encodes 5-enol-pyruvylshikimate-3-phosphate synthase and confers resistance to glyphosate herbicide. Evidence for gene flow to 75 of 138 sentinel plants of A. stolonifera and to 29 of 69 resident Agrostis plants was based on seedling progeny survival after spraying with glyphosate in greenhouse assays and positive TraitChek, PCR, and sequencing results. Additional studies are needed to determine whether introgression will occur and whether it will affect the ecological fitness of progeny or the structure of plant communities in which transgenic progeny may become established.

Milk in the diet: good or bad for vascular disease?

PubMed

Givens, D I

2012-02-01

CVD still represent the greatest cause of death and disease burden in Europe and there remains uncertainty whether or not diets rich in milk and/or dairy products affect CVD risk. This paper reviews current evidence on this from prospective studies and the role of serum lipids and blood pressure as markers of CVD risk with such diets. Also the potential of animal nutrition-based approaches aimed at reducing CVD risk from consumption of milk and dairy products is outlined. Briefly, the evidence from prospective studies indicates that increased consumption of milk does not result in increased CVD risk and may give some long-term benefits, although few studies relate specifically to cheese and butter and more information on the relationship between milk/dairy product consumption and dementia is needed. Recent data suggest that the SFA in dairy products may be less of a risk factor than previously thought; although this is based on serum cholesterol responses which taken in isolation may be misleading. Milk and some dairy products have counterbalancing effects by reducing blood pressure and possibly BMI control. Despite this, animal nutrition strategies to replace some SFA in milk with cis-MUFA or cis-PUFA are extensive and intuitively beneficial, although this remains largely unproven, especially for milk. There is an urgent need for robust intervention studies to evaluate such milk-fat modifications using holistic markers of CVD risk including central arterial stiffness.

Lower bone turnover markers in metabolic syndrome and diabetes: the population-based Study of Health in Pomerania.

PubMed

Lerchbaum, E; Schwetz, V; Nauck, M; Völzke, H; Wallaschofski, H; Hannemann, A

2015-05-01

Accumulating evidence demonstrates an important interaction between bone and energy metabolism. We aimed to study the associations of three bone turnover markers (BTM: osteocalcin, beta-crosslaps, procollagen type 1 N-terminal propeptide) as well as of 25-hydroxyvitamin D and parathyroid hormone with metabolic syndrome (MetS) or type 2 diabetes mellitus (T2DM) in a large population-based cohort. This cross-sectional study comprised 2671 adult men and women participating in the first follow-up of the population-based Study of Health in Pomerania (SHIP-1). Multivariable logistic regression analyses were performed to assess sex-specific associations between the BTMs, 25-hydroxyvitamin D or parathyroid hormone and metabolic disease. All models were adjusted for age, body mass index, smoking status, physical activity, estimated glomerular filtration rate and month of blood sampling. The models for women were further adjusted for menopausal status. Higher BTM or 25-hydroxyvitamin D concentrations were associated with significantly lower odds for metabolic disease, while there was no association between parathyroid hormone and MetS or T2DM. Our results contribute to the accumulating evidence of a cross-sectional association between high BTM or 25-hydroxyvitamin D concentrations and a lower prevalence of MetS or T2DM. Further research is necessary to evaluate the mechanisms underlying these results. Copyright © 2015 Elsevier B.V. All rights reserved.

Pleiotropic genes for metabolic syndrome and inflammation

PubMed Central

Kraja, Aldi T.; Chasman, Daniel I.; North, Kari E.; Reiner, Alexander P.; Yanek, Lisa R.; Kilpeläinen, Tuomas O.; Smith, Jennifer A.; Dehghan, Abbas; Dupuis, Josée; Johnson, Andrew D.; Feitosa, Mary F.; Tekola-Ayele, Fasil; Chu, Audrey Y.; Nolte, Ilja M.; Dastani, Zari; Morris, Andrew; Pendergrass, Sarah A.; Sun, Yan V.; Ritchie, Marylyn D.; Vaez, Ahmad; Lin, Honghuang; Ligthart, Symen; Marullo, Letizia; Rohde, Rebecca; Shao, Yaming; Ziegler, Mark A.; Im, Hae Kyung; Schnabel, Renate B.; Jørgensen, Torben; Jørgensen, Marit E.; Hansen, Torben; Pedersen, Oluf; Stolk, Ronald P.; Snieder, Harold; Hofman, Albert; Uitterlinden, Andre G.; Franco, Oscar H.; Ikram, M. Arfan; Richards, J. Brent; Rotimi, Charles; Wilson, James G.; Lange, Leslie; Ganesh, Santhi K.; Nalls, Mike; Rasmussen-Torvik, Laura J.; Pankow, James S.; Coresh, Josef; Tang, Weihong; Kao, W.H. Linda; Boerwinkle, Eric; Morrison, Alanna C.; Ridker, Paul M.; Becker, Diane M.; Rotter, Jerome I.; Kardia, Sharon L.R.; Loos, Ruth J.F.; Larson, Martin G.; Hsu, Yi-Hsiang; Province, Michael A.; Tracy, Russell; Voight, Benjamin F.; Vaidya, Dhananjay; O’Donnell, Christopher; Benjamin, Emelia J.; Alizadeh, Behrooz Z.; Prokopenko, Inga; Meigs, James B.; Borecki, Ingrid B.

2014-01-01

Metabolic syndrome (MetS) has become a health and financial burden worldwide. The MetS definition captures clustering of risk factors that predict higher risk for diabetes mellitus and cardiovascular disease. Our study hypothesis is that additional to genes influencing individual MetS risk factors, genetic variants exist that influence MetS and inflammatory markers forming a predisposing MetS genetic network. To test this hypothesis a staged approach was undertaken. (a) We analyzed 17 metabolic and inflammatory traits in more than 85,500 participants from 14 large epidemiological studies within the Cross Consortia Pleiotropy Group. Individuals classified with MetS (NCEP definition), versus those without, showed on average significantly different levels for most inflammatory markers studied. (b) Paired average correlations between 8 metabolic traits and 9 inflammatory markers from the same studies as above, estimated with two methods, and factor analyses on large simulated data, helped in identifying 8 combinations of traits for follow-up in meta-analyses, out of 130,305 possible combinations between metabolic traits and inflammatory markers studied. (c) We performed correlated meta-analyses for 8 metabolic traits and 6 inflammatory markers by using existing GWAS published genetic summary results, with about 2.5 million SNPs from twelve predominantly largest GWAS consortia. These analyses yielded 130 unique SNPs/genes with pleiotropic associations (a SNP/gene associating at least one metabolic trait and one inflammatory marker). Of them twenty-five variants (seven loci newly reported) are proposed as MetS candidates. They map to genes MACF1, KIAA0754, GCKR, GRB14, COBLL1, LOC646736-IRS1, SLC39A8, NELFE, SKIV2L, STK19, TFAP2B, BAZ1B, BCL7B, TBL2, MLXIPL, LPL, TRIB1, ATXN2, HECTD4, PTPN11, ZNF664, PDXDC1, FTO, MC4R and TOMM40. Based on large data evidence, we conclude that inflammation is a feature of MetS and several gene variants show pleiotropic genetic associations across phenotypes and might explain a part of MetS correlated genetic architecture. These findings warrant further functional investigation. PMID:24981077

Pleiotropic genes for metabolic syndrome and inflammation.

PubMed

Kraja, Aldi T; Chasman, Daniel I; North, Kari E; Reiner, Alexander P; Yanek, Lisa R; Kilpeläinen, Tuomas O; Smith, Jennifer A; Dehghan, Abbas; Dupuis, Josée; Johnson, Andrew D; Feitosa, Mary F; Tekola-Ayele, Fasil; Chu, Audrey Y; Nolte, Ilja M; Dastani, Zari; Morris, Andrew; Pendergrass, Sarah A; Sun, Yan V; Ritchie, Marylyn D; Vaez, Ahmad; Lin, Honghuang; Ligthart, Symen; Marullo, Letizia; Rohde, Rebecca; Shao, Yaming; Ziegler, Mark A; Im, Hae Kyung; Schnabel, Renate B; Jørgensen, Torben; Jørgensen, Marit E; Hansen, Torben; Pedersen, Oluf; Stolk, Ronald P; Snieder, Harold; Hofman, Albert; Uitterlinden, Andre G; Franco, Oscar H; Ikram, M Arfan; Richards, J Brent; Rotimi, Charles; Wilson, James G; Lange, Leslie; Ganesh, Santhi K; Nalls, Mike; Rasmussen-Torvik, Laura J; Pankow, James S; Coresh, Josef; Tang, Weihong; Linda Kao, W H; Boerwinkle, Eric; Morrison, Alanna C; Ridker, Paul M; Becker, Diane M; Rotter, Jerome I; Kardia, Sharon L R; Loos, Ruth J F; Larson, Martin G; Hsu, Yi-Hsiang; Province, Michael A; Tracy, Russell; Voight, Benjamin F; Vaidya, Dhananjay; O'Donnell, Christopher J; Benjamin, Emelia J; Alizadeh, Behrooz Z; Prokopenko, Inga; Meigs, James B; Borecki, Ingrid B

2014-08-01

Metabolic syndrome (MetS) has become a health and financial burden worldwide. The MetS definition captures clustering of risk factors that predict higher risk for diabetes mellitus and cardiovascular disease. Our study hypothesis is that additional to genes influencing individual MetS risk factors, genetic variants exist that influence MetS and inflammatory markers forming a predisposing MetS genetic network. To test this hypothesis a staged approach was undertaken. (a) We analyzed 17 metabolic and inflammatory traits in more than 85,500 participants from 14 large epidemiological studies within the Cross Consortia Pleiotropy Group. Individuals classified with MetS (NCEP definition), versus those without, showed on average significantly different levels for most inflammatory markers studied. (b) Paired average correlations between 8 metabolic traits and 9 inflammatory markers from the same studies as above, estimated with two methods, and factor analyses on large simulated data, helped in identifying 8 combinations of traits for follow-up in meta-analyses, out of 130,305 possible combinations between metabolic traits and inflammatory markers studied. (c) We performed correlated meta-analyses for 8 metabolic traits and 6 inflammatory markers by using existing GWAS published genetic summary results, with about 2.5 million SNPs from twelve predominantly largest GWAS consortia. These analyses yielded 130 unique SNPs/genes with pleiotropic associations (a SNP/gene associating at least one metabolic trait and one inflammatory marker). Of them twenty-five variants (seven loci newly reported) are proposed as MetS candidates. They map to genes MACF1, KIAA0754, GCKR, GRB14, COBLL1, LOC646736-IRS1, SLC39A8, NELFE, SKIV2L, STK19, TFAP2B, BAZ1B, BCL7B, TBL2, MLXIPL, LPL, TRIB1, ATXN2, HECTD4, PTPN11, ZNF664, PDXDC1, FTO, MC4R and TOMM40. Based on large data evidence, we conclude that inflammation is a feature of MetS and several gene variants show pleiotropic genetic associations across phenotypes and might explain a part of MetS correlated genetic architecture. These findings warrant further functional investigation. Copyright © 2014 Elsevier Inc. All rights reserved.

Evidence of substantial recombination among Trypanosoma cruzi II strains from Minas Gerais.

PubMed

Baptista, Rodrigo de Paula; D'Ávila, Daniella Alchaar; Segatto, Marcela; do Valle, Ítalo Faria; Franco, Glória Regina; Valadares, Helder Magno Silva; Gontijo, Eliane Dias; Galvão, Lúcia Maria da Cunha; Pena, Sérgio Danilo Junho; Chiari, Egler; Machado, Carlos Renato; Macedo, Andréa Mara

2014-03-01

Due to the scarcity of evidence of sexuality in Trypanosoma cruzi, the causative agent of Chagas disease, it has been general accepted that the parasite reproduction is essentially clonal with infrequent genetic recombination. This assumption is mainly supported by indirect evidence, such as Hardy-Weinberg imbalances, linkage disequilibrium and a strong correlation between independent sets of genetic markers of T. cruzi populations. However, because the analyzed populations are usually isolated from different geographic regions, the possibility of population substructuring as generating these genetic marker imbalances cannot be eliminated. To investigate this possibility, we firstly compared the allele frequencies and haplotype networks using seven different polymorphic loci (two from mitochondrial and five from different nuclear chromosomes) in two groups of TcII strains: one including isolates obtained from different regions in Latin America and the other including isolates obtained only from patients of the Minas Gerais State in Brazil. Our hypothesis was that if the population structure is essentially clonal, Hardy-Weinberg disequilibrium and a sharp association between the clusters generated by analyzing independent markers should be observed in both strain groups, independent of the geographic origin of the samples. The results demonstrated that the number of microsatellite loci in linkage disequilibrium decreased from 4 to 1 when only strains from Minas Gerais were analyzed. Moreover, we did not observed any correlation between the clusters when analyzing the nuclear and mitochondrial loci, suggesting independent inheritance of these markers among the Minas Gerais strains. Besides, using a second subset of five physically linked microsatellite loci and the Minas Gerais strains, we could also demonstrate evidence of homologous recombination roughly proportional to the relative distance among them. Taken together, our results do not support a clonal population structure for T. cruzi, particularly in TcII, which coexists in the same geographical area, suggesting that genetic exchanges among these strains may occur more frequently than initially expected. Copyright © 2013 Elsevier B.V. All rights reserved.

Toolbox Approaches Using Molecular Markers and 16S rRNA Gene Amplicon Data Sets for Identification of Fecal Pollution in Surface Water.

PubMed

Ahmed, W; Staley, C; Sadowsky, M J; Gyawali, P; Sidhu, J P S; Palmer, A; Beale, D J; Toze, S

2015-10-01

In this study, host-associated molecular markers and bacterial 16S rRNA gene community analysis using high-throughput sequencing were used to identify the sources of fecal pollution in environmental waters in Brisbane, Australia. A total of 92 fecal and composite wastewater samples were collected from different host groups (cat, cattle, dog, horse, human, and kangaroo), and 18 water samples were collected from six sites (BR1 to BR6) along the Brisbane River in Queensland, Australia. Bacterial communities in the fecal, wastewater, and river water samples were sequenced. Water samples were also tested for the presence of bird-associated (GFD), cattle-associated (CowM3), horse-associated, and human-associated (HF183) molecular markers, to provide multiple lines of evidence regarding the possible presence of fecal pollution associated with specific hosts. Among the 18 water samples tested, 83%, 33%, 17%, and 17% were real-time PCR positive for the GFD, HF183, CowM3, and horse markers, respectively. Among the potential sources of fecal pollution in water samples from the river, DNA sequencing tended to show relatively small contributions from wastewater treatment plants (up to 13% of sequence reads). Contributions from other animal sources were rarely detected and were very small (<3% of sequence reads). Source contributions determined via sequence analysis versus detection of molecular markers showed variable agreement. A lack of relationships among fecal indicator bacteria, host-associated molecular markers, and 16S rRNA gene community analysis data was also observed. Nonetheless, we show that bacterial community and host-associated molecular marker analyses can be combined to identify potential sources of fecal pollution in an urban river. This study is a proof of concept, and based on the results, we recommend using bacterial community analysis (where possible) along with PCR detection or quantification of host-associated molecular markers to provide information on the sources of fecal pollution in waterways. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Genetic diversity and structure of wild populations of Carica papaya in Northern Mesoamerica inferred by nuclear microsatellites and chloroplast markers

PubMed Central

Chávez-Pesqueira, Mariana; Núñez-Farfán, Juan

2016-01-01

Background and aims Few studies have evaluated the genetic structure and evolutionary history of wild varieties of important crop species. The wild papaya (Carica papaya) is a key element of early successional tropical and sub-tropical forests in Mexico, and constitutes the genetic reservoir for evolutionary potential of the species. In this study we aimed to determine how diverse and structured is the genetic variability of wild populations of C. papaya in Northern Mesoamerica. Moreover, we assessed if genetic structure and evolutionary history coincide with hypothetized (1) pre-Pleistocene events (Isthmus of Tehuantepec sinking), (2) Pleistocene refugia or (3) recent patterns. Methods We used six nuclear and two chloroplast (cp) DNA markers to assess the genetic diversity and phylogeographical structure of 19 wild populations of C. papaya in its natural distribution in Northern Mesoamerica. Key Results We found high genetic diversity (Ho = 0·681 for nuclear markers, and h = 0·701 for cpDNA markers) and gene flow between populations of C. papaya (migration r up to 420 km). A lack of phylogeographical structure was found with the cpDNA markers (NST < GST), whereas a recent population structure was inferred with the nuclear markers. Evidence indicates that pre-Pleistocene events or refugia did not play an important role in the genetic structuring of wild papaya. Conclusions Because of its life history characteristics and lack of an ancient phylogeographical structure found with the cpDNA markers, we suggest that C. papaya was dispersed throughout the lowland rain forests of Mexico (along the coastal plains and foothills of Sierras). This scenario supports the hypothesis that tropical forests in Northern Mesoamerica did not experience important climate fluctuations during the Pleistocene, and that the life history of C. papaya could have promoted long-distance dispersal and rapid colonization of lowland rainforests. Moreover, the results obtained with the nuclear markers suggest recent human disturbances. The fragmentation of tropical habitats in Northern Mesoamerica appears to be the main driver of genetic structuring, and the major threat to the dispersion and survival of the species in the wild. PMID:27974326

Chemical and biological diversity of Bergamot (Citrus bergamia) in relation to environmental factors.

PubMed

Statti, Giancarlo A; Conforti, Filomena; Sacchetti, Gianni; Muzzoli, Mariavittoria; Agrimonti, Caterina; Menichini, Francesco

2004-03-01

Oil of bergamot is receiving renewed popularity in aromatherapy. The biovariability of Citrus bergamia grown wild in Calabria (Italy) was investigated as far as chemical markers (linalool, linalyl acetate and bergapten) content and antioxidant and antifungal activities of the methanolic extracts. The average content in the markers presents slight variations with the altitude and more evident changes with the latitude of the areas of plant collection.

Insights into population ecology and sexual selection in snakes through the application of DNA-based genetic markers.

PubMed

Gibbs, H L; Weatherhead, P J

2001-01-01

Hypervariable genetic markers have revolutionized studies of kinship, behavioral ecology, and population biology in vertebrate groups such as birds, but their use in snakes remains limited. To illustrate the value of such markers in snakes, we review studies that have used microsatellite DNA loci to analyze local population differentiation and parentage in snakes. Four ecologically distinct species of snakes all show evidence for differentiation at small spatial scales (2-15 km), but with substantial differences among species. This result highlights how genetic analysis can reveal hidden aspects of the natural history of difficult-to-observe taxa, and it raises important questions about the ecological factors that may contribute to restricted gene flow. A 3-year study of genetic parentage in marked populations of the northern water snake showed that (1) participation in mating aggregations was a poor predictor of genetic-based measures of reproductive success; (2) multiple paternity was high, yet there was no detectable fitness advantage to multiple mating by females; and (3) the opportunity for selection was far higher in males than in females due to a larger variance in male reproductive success, and yet this resulted in no detectable selection on morphological variation in males. Thus genetic markers have provided accurate measures of individual reproductive success in this species, an important step toward resolving the adaptive significance of key features including multiple paternity and reversed sexual size dimorphism. Overall these studies illustrate how genetic analyses of snakes provide previously unobtainable information of long-standing interest to behavioral ecologists.

Distinctive mitochondrial genome of Calanoid copepod Calanus sinicus with multiple large non-coding regions and reshuffled gene order: Useful molecular markers for phylogenetic and population studies

PubMed Central

2011-01-01

Background Copepods are highly diverse and abundant, resulting in extensive ecological radiation in marine ecosystems. Calanus sinicus dominates continental shelf waters in the northwest Pacific Ocean and plays an important role in the local ecosystem by linking primary production to higher trophic levels. A lack of effective molecular markers has hindered phylogenetic and population genetic studies concerning copepods. As they are genome-level informative, mitochondrial DNA sequences can be used as markers for population genetic studies and phylogenetic studies. Results The mitochondrial genome of C. sinicus is distinct from other arthropods owing to the concurrence of multiple non-coding regions and a reshuffled gene arrangement. Further particularities in the mitogenome of C. sinicus include low A + T-content, symmetrical nucleotide composition between strands, abbreviated stop codons for several PCGs and extended lengths of the genes atp6 and atp8 relative to other copepods. The monophyletic Copepoda should be placed within the Vericrustacea. The close affinity between Cyclopoida and Poecilostomatoida suggests reassigning the latter as subordinate to the former. Monophyly of Maxillopoda is rejected. Within the alignment of 11 C. sinicus mitogenomes, there are 397 variable sites harbouring three 'hotspot' variable sites and three microsatellite loci. Conclusion The occurrence of the circular subgenomic fragment during laboratory assays suggests that special caution should be taken when sequencing mitogenomes using long PCR. Such a phenomenon may provide additional evidence of mitochondrial DNA recombination, which appears to have been a prerequisite for shaping the present mitochondrial profile of C. sinicus during its evolution. The lack of synapomorphic gene arrangements among copepods has cast doubt on the utility of gene order as a useful molecular marker for deep phylogenetic analysis. However, mitochondrial genomic sequences have been valuable markers for resolving phylogenetic issues concerning copepods. The variable site maps of C. sinicus mitogenomes provide a solid foundation for population genetic studies. PMID:21269523

Individual genetic diversity and probability of infection by avian malaria parasites in blue tits (Cyanistes caeruleus).

PubMed

Ferrer, E S; García-Navas, V; Sanz, J J; Ortego, J

2014-11-01

Understanding the importance of host genetic diversity for coping with parasites and infectious diseases is a long-standing goal in evolutionary biology. Here, we study the association between probability of infection by avian malaria (Plasmodium relictum) and individual genetic diversity in three blue tit (Cyanistes caeruleus) populations that strongly differ in prevalence of this parasite. For this purpose, we screened avian malaria infections and genotyped 789 blue tits across 26 microsatellite markers. We used two different arrays of markers: 14 loci classified as neutral and 12 loci classified as putatively functional. We found a significant relationship between probability of infection and host genetic diversity estimated at the subset of neutral markers that was not explained by strong local effects and did not differ among the studied populations. This relationship was not linear, and probability of infection increased up to values of homozygosity by locus (HL) around 0.15, reached a plateau at values of HL from 0.15 to 0.40 and finally declined among a small proportion of highly homozygous individuals (HL > 0.4). We did not find evidence for significant identity disequilibrium, which may have resulted from a low variance of inbreeding in the study populations and/or the small power of our set of markers to detect it. A combination of subtle positive and negative local effects and/or a saturation threshold in the association between probability of infection and host genetic diversity in combination with increased resistance to parasites in highly homozygous individuals may explain the observed negative quadratic relationship. Overall, our study highlights that parasites play an important role in shaping host genetic variation and suggests that the use of large sets of neutral markers may be more appropriate for the study of heterozygosity-fitness correlations. © 2014 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

Disturbances in reality testing as markers of risk in offspring of parents with bipolar disorder: a systematic review from a developmental psychopathology perspective

PubMed Central

Narayan, Angela J; Allen, Timothy A; Cullen, Kathryn R; Klimes-Dougan, Bonnie

2013-01-01

Objectives This comprehensive review examined the prevalence and progression of disturbances in reality testing (DRT), defined as psychotic symptoms, cognitive disruptions, and thought problems, in offspring of parents with bipolar disorder (O-BD). Our approach was grounded in a developmental psychopathology perspective and considered a broader phenotype of risk within the bipolar–schizophrenia spectrum as measured by categorical and dimensional assessments of DRT in high-risk youth. Methods Relevant studies were identified from numerous sources (e.g., PubMed, reference sections, and colleagues). Inclusion criteria were: (i) family risk studies published between 1975 and 2012 in which O-BD were contrasted with a comparison group (e.g., offspring of parents who had other psychiatric disorders or were healthy) on DRT outcomes and (ii) results reported for categorical or dimensional assessments of DRT (e.g., schizophrenia, psychotic symptoms, cluster A personality traits, or thought problems), yielding a total of 23 studies. Results Three key findings emerged: (i) categorical approaches of DRT in O-BD produced low incidence base rates and almost no evidence of significant differences in DRT between O-BD and comparison groups, whereas (ii) many studies using dimensional assessments of DRT yielded significant group differences in DRT. Furthermore, (iii) preliminary evidence from dimensional measures suggested that the developmental progression of DRT in O-BD might represent a prodrome of severe psychological impairment. Conclusions Preliminary but promising evidence suggests that DRT is a probable marker of risk for future impairment in O-BD. Methodological strengths and weaknesses, the psychometric properties of primary DRT constructs, and future directions for developmental and longitudinal research with O-BD are discussed. PMID:24034419

Suggestive evidence for association between L-type voltage-gated calcium channel (CACNA1C) gene haplotypes and bipolar disorder in Latinos: a family-based association study

PubMed Central

Gonzalez, Suzanne; Xu, Chun; Ramirez, Mercedes; Zavala, Juan; Armas, Regina; Contreras, Salvador A; Contreras, Javier; Dassori, Albana; Leach, Robin J; Flores, Deborah; Jerez, Alvaro; Raventós, Henriette; Ontiveros, Alfonso; Nicolini, Humberto; Escamilla, Michael

2013-01-01

Objectives Through recent genome-wide association studies (GWAS), several groups have reported significant association between variants in the alpha 1C subunit of the L-type voltage-gated calcium channel (CACNA1C) and bipolar disorder (BP) in European and European-American cohorts. We performed a family-based association study to determine whether CACNA1C is associated with BP in the Latino population. Methods This study consisted of 913 individuals from 215 Latino pedigrees recruited from the United States, Mexico, Guatemala, and Costa Rica. The Illumina GoldenGate Genotyping Assay was used to genotype 58 single-nucleotide polymorphisms (SNPs) that spanned a 602.9 kb region encompassing the CACNA1C gene including two SNPs (rs7297582 and rs1006737) previously shown to associate with BP. Individual SNP and haplotype association analyses were performed using Family-Based Association Test (version 2.0.3) and Haploview (version 4.2) software. Results An eight-locus haplotype block that included these two markers showed significant association with BP (global marker permuted p = 0.0018) in the Latino population. For individual SNPs, this sample had insufficient power (10%) to detect associations with SNPs with minor effect (odds ratio = 1.15). Conclusions Although we were not able to replicate findings of association between individual CACNA1C SNPs rs7297582 and rs1006737 and BP, we were able to replicate the GWAS signal reported for CACNA1C through a haplotype analysis that encompassed these previously reported significant SNPs. These results provide additional evidence that CACNA1C is associated with BP and provides the first evidence that variations in this gene might play a role in the pathogenesis of this disorder in the Latino population. PMID:23437964

The likelihood ratio as a random variable for linked markers in kinship analysis.

PubMed

Egeland, Thore; Slooten, Klaas

2016-11-01

The likelihood ratio is the fundamental quantity that summarizes the evidence in forensic cases. Therefore, it is important to understand the theoretical properties of this statistic. This paper is the last in a series of three, and the first to study linked markers. We show that for all non-inbred pairwise kinship comparisons, the expected likelihood ratio in favor of a type of relatedness depends on the allele frequencies only via the number of alleles, also for linked markers, and also if the true relationship is another one than is tested for by the likelihood ratio. Exact expressions for the expectation and variance are derived for all these cases. Furthermore, we show that the expected likelihood ratio is a non-increasing function if the recombination rate increases between 0 and 0.5 when the actual relationship is the one investigated by the LR. Besides being of theoretical interest, exact expressions such as obtained here can be used for software validation as they allow to verify the correctness up to arbitrary precision. The paper also presents results and advice of practical importance. For example, we argue that the logarithm of the likelihood ratio behaves in a fundamentally different way than the likelihood ratio itself in terms of expectation and variance, in agreement with its interpretation as weight of evidence. Equipped with the results presented and freely available software, one may check calculations and software and also do power calculations.

Uniparental disomy for chromosome 6 results in steroid 21-hydroxylase deficiency: evidence of different genetic mechanisms involved in the production of the disease.

PubMed Central

López-Gutiérrez, A U; Riba, L; Ordoñez-Sánchez, M L; Ramírez-Jiménez, S; Cerrillo-Hinojosa, M; Tusié-Luna, M T

1998-01-01

Congenital adrenal hyperplasia (CAH) is an inherited recessive disorder of adrenal steroidogenesis caused by mutations in the steroid 21-hydroxylase gene (CYP21) in more than 90% of affected patients. The CYP21 gene is located within the HLA complex locus on chromosome 6 (6p21.3). During a molecular characterisation study of a group of 47 Mexican families with 21-hydroxylase deficiency, we identified nine in which the mutation or mutations found in the patient did not appear to originate from one of the parents. Through DNA fingerprinting, paternity was established in all nine families with a probability of non-paternity in the range of 10(-19) to 10(-23). Among these families, we identified one patient with exclusive paternal inheritance of all eight markers tested on chromosome 6p, despite normal maternal and paternal contributions for eight additional markers on three different chromosomes. We did not identify duplication of paternal information for markers in the 6q region, consistent with lack of expression of transient neonatal diabetes owing to genomic imprinting in this patient. Our results substantiate evidence for the existence of different genetic mechanisms involved in the expression of this recessive condition in a substantial portion (approximately 19%) of affected Mexican families. In addition to the identification of a patient with paternal uniparental disomy, the occurrence of germline mutations may explain the unusual pattern of segregation in the majority of the remaining eight families. PMID:9863599

Translational safety biomarkers of colonic barrier integrity in the rat.

PubMed

Erkens, Tim; Bueters, Ruud; van Heerden, Marjolein; Cuyckens, Filip; Vreeken, Rob; Goeminne, Nick; Lammens, Lieve

2018-05-20

The intestinal barrier controls intestinal permeability, and its disruption has been associated with multiple diseases. Therefore, preclinical safety biomarkers monitoring barrier integrity are essential during the development of drugs targeting the intestines, particularly if starting treatment early after onset of disease. Classical toxicology endpoints are not sensitive enough and therefore our objective was to identify non-invasive markers enabling early in vivo detection of colonic barrier perturbation. Male Sprague-Dawley rats were dosed intracolonically via the rectum, using sodium caprate or ibuprofen as tool compounds to alter barrier integrity. Several potentially translational biomarkers and probe molecules related to permeability, inflammation or tissue damage were evaluated, using various analytical platforms, including immunoassays, targeted metabolomics and highly sensitive ultra-performance liquid chromatography-tandem mass spectrometry. Several markers were identified that allow early in vivo detection of colonic barrier integrity changes, before histopathological evidence of tissue damage. The most promising permeability markers identified were plasma fluorescein isothiocyanate-dextran 4000 and a lactulose/mannitol/sucralose mixture in urine. These markers showed maximum increases over 100-fold or approximately 10-50-fold, respectively. Intracolonic administration of the above probe molecules outperformed oral administration and inflammatory or other biomarkers, such as α 2 -macroglobulin, calprotectin, cytokines, prostaglandins and a panel of metabolic molecules to identify early and subtle changes in barrier integrity. However, optimal timing of probe administration and sample collection is important for all markers evaluated. Inclusion of these probe molecules in preclinical toxicity studies might aid in risk assessment and the design of a clinical biomarker plan, as several of these markers have translational potential. Copyright © 2018 John Wiley & Sons, Ltd.

Chitinase enzyme activity in CSF is a powerful biomarker of Alzheimer disease.

PubMed

Watabe-Rudolph, M; Song, Z; Lausser, L; Schnack, C; Begus-Nahrmann, Y; Scheithauer, M-O; Rettinger, G; Otto, M; Tumani, H; Thal, D R; Attems, J; Jellinger, K A; Kestler, H A; von Arnim, C A F; Rudolph, K L

2012-02-21

DNA damage accumulation in brain is associated with the development of Alzheimer disease (AD), but newly identified protein markers of DNA damage have not been evaluated in the diagnosis of AD and other forms of dementia. Here, we analyzed the level of novel biomarkers of DNA damage and telomere dysfunction (chitinase activity, N-acetyl-glucosaminidase activity, stathmin, and EF-1α) in CSF of 94 patients with AD, 41 patients with non-AD dementia, and 40 control patients without dementia. Enzymatic activity of chitinase (chitotriosidase activity) and stathmin protein level were significantly increased in CSF of patients with AD and non-AD dementia compared with that of no dementia control patients. As a single marker, chitinase activity was most powerful for distinguishing patients with AD from no dementia patients with an accuracy of 85.8% using a single threshold. Discrimination was even superior to clinically standard CSF markers that showed an accuracy of 78.4% (β-amyloid) and 77.6% (tau). Combined analysis of chitinase with other markers increased the accuracy to a maximum of 91%. The biomarkers of DNA damage were also increased in CSF of patients with non-AD dementia compared with no dementia patients, and the new biomarkers improved the diagnosis of non-AD dementia as well as the discrimination of AD from non-AD dementia. Taken together, the findings in this study provide experimental evidence that DNA damage markers are significantly increased in AD and non-AD dementia. The biomarkers identified outperformed the standard CSF markers for diagnosing AD and non-AD dementia in the cohort investigated.

Haplotype-based identification of a microsomal transfer protein marker associated with the human lifespan

PubMed Central

Geesaman, Bard J.; Benson, Erica; Brewster, Stephanie J.; Kunkel, Louis M.; Blanché, Hélène; Thomas, Gilles; Perls, Thomas T.; Daly, Mark J.; Puca, Annibale A.

2003-01-01

We previously reported a genomewide linkage study for human longevity using 308 long-lived individuals (LLI) (centenarians or near-centenarians) in 137 sibships and identified statistically significant linkage within chromosome 4 near microsatellite D4S1564. This interval spans 12 million bp and contains ≈50 putative genes. To identify the specific gene and gene variants impacting lifespan, we performed a haplotype-based fine-mapping study of the interval. The resulting genetic association study identified a haplotype marker within microsomal transfer protein as a modifier of human lifespan. This same variant was tested in a second cohort of LLI from France, and although the association was not replicated, there was evidence for statistical distortion in the form of Hardy–Weinberg disequilibrium. Microsomal transfer protein has been identified as the rate-limiting step in lipoprotein synthesis and may affect longevity by subtly modulating this pathway. This study provides proof of concept for the feasibility of using the genomes of LLI to identify genes impacting longevity. PMID:14615589

A novel statistical approach shows evidence for multi-system physiological dysregulation during aging.

PubMed

Cohen, Alan A; Milot, Emmanuel; Yong, Jian; Seplaki, Christopher L; Fülöp, Tamàs; Bandeen-Roche, Karen; Fried, Linda P

2013-03-01

Previous studies have identified many biomarkers that are associated with aging and related outcomes, but the relevance of these markers for underlying processes and their relationship to hypothesized systemic dysregulation is not clear. We address this gap by presenting a novel method for measuring dysregulation via the joint distribution of multiple biomarkers and assessing associations of dysregulation with age and mortality. Using longitudinal data from the Women's Health and Aging Study, we selected a 14-marker subset from 63 blood measures: those that diverged from the baseline population mean with age. For the 14 markers and all combinatorial sub-subsets we calculated a multivariate distance called the Mahalanobis distance (MHBD) for all observations, indicating how "strange" each individual's biomarker profile was relative to the baseline population mean. In most models, MHBD correlated positively with age, MHBD increased within individuals over time, and higher MHBD predicted higher risk of subsequent mortality. Predictive power increased as more variables were incorporated into the calculation of MHBD. Biomarkers from multiple systems were implicated. These results support hypotheses of simultaneous dysregulation in multiple systems and confirm the need for longitudinal, multivariate approaches to understanding biomarkers in aging. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Evaluation of In Vivo Wound Healing Activity of Bacopa monniera on Different Wound Model in Rats

PubMed Central

Murthy, S.; Gautam, M. K.; Goel, Shalini; Purohit, V.; Sharma, H.; Goel, R. K.

2013-01-01

Wound healing effects of 50% ethanol extract of dried whole plant of Bacopa monniera (BME) was studied on wound models in rats. BME (25 mg/kg) was administered orally, once daily for 10 days (incision and dead space wound models) or for 21 days or more (excision wound model) in rats. BME was studied for its in vitro antimicrobial and in vivo wound breaking strength, WBS (incision model), rate of contraction, period of epithelization, histology of skin (excision model), granulation tissue free radicals (nitric oxide and lipid peroxidation), antioxidants (catalase, superoxide dismutase, and reduced glutathione), acute inflammatory marker (myeloperoxidase), connective tissue markers (hydroxyproline, hexosamine, and hexuronic acid), and deep connective tissue histology (dead space wound). BME showed antimicrobial activity against skin pathogens, enhanced WBS, rate of contraction, skin collagen tissue formation, and early epithelization period with low scar area indicating enhanced healing. Healing effect was further substantiated by decreased free radicals and myeloperoxidase and enhanced antioxidants and connective tissue markers with histological evidence of more collagen formation in skin and deeper connective tissues. BME decreased myeloperoxidase and free radical generated tissue damage, promoting antioxidant status, faster collagen deposition, other connective tissue constituent formation, and antibacterial activity. PMID:23984424

Effects of DGAT1 gene on meat and carcass fatness quality in Chinese commercial cattle.

PubMed

Yuan, Zhengrong; Li, Junya; Li, Jiao; Gao, Xue; Gao, Huijiang; Xu, Shangzhong

2013-02-01

This study was designed to investigate the candidate single nucleotide polymorphisms (SNPs) in the exon's region of bovine diacylglycerol O-acyltransferase (DGAT1) gene using bioinformatics and experimental methods. A total of 17 SNPs were screened from public data resources and DNA sequencing. Three SNPs (c.572A>G, c.1241C>T and c.1416T>G) of these candidate SNPs were genotyped by created restriction site-polymerase chain reaction (CRS-PCR) methods. The gene-specific SNP markers and their effects on meat and carcass fatness quality traits were evaluated in Chinese commercial cattle. The c.572A>G and c.1416T>G significantly effected on backfat thickness, longissimus muscle area, marbling score, fat color and Warner-Bratzler shear force. No significant association was detected between the c.1241C>T and measured traits. Results from this study suggested that the SNP markers may be effective for the marker-assisted selection of meat and carcass fatness quality traits, and added new evidence that DGAT1 gene is an important candidate gene for the improvement of meat and carcass fatness quality in beef cattle industry.

Evaluation of in vivo wound healing activity of Bacopa monniera on different wound model in rats.

PubMed

Murthy, S; Gautam, M K; Goel, Shalini; Purohit, V; Sharma, H; Goel, R K

2013-01-01

Wound healing effects of 50% ethanol extract of dried whole plant of Bacopa monniera (BME) was studied on wound models in rats. BME (25 mg/kg) was administered orally, once daily for 10 days (incision and dead space wound models) or for 21 days or more (excision wound model) in rats. BME was studied for its in vitro antimicrobial and in vivo wound breaking strength, WBS (incision model), rate of contraction, period of epithelization, histology of skin (excision model), granulation tissue free radicals (nitric oxide and lipid peroxidation), antioxidants (catalase, superoxide dismutase, and reduced glutathione), acute inflammatory marker (myeloperoxidase), connective tissue markers (hydroxyproline, hexosamine, and hexuronic acid), and deep connective tissue histology (dead space wound). BME showed antimicrobial activity against skin pathogens, enhanced WBS, rate of contraction, skin collagen tissue formation, and early epithelization period with low scar area indicating enhanced healing. Healing effect was further substantiated by decreased free radicals and myeloperoxidase and enhanced antioxidants and connective tissue markers with histological evidence of more collagen formation in skin and deeper connective tissues. BME decreased myeloperoxidase and free radical generated tissue damage, promoting antioxidant status, faster collagen deposition, other connective tissue constituent formation, and antibacterial activity.

Novel tools for blood inflammatory markers detection in monitoring air pollution-induced cardio-respiratory symptoms.

PubMed

Coccini, Teresa; Manzo, Luigi; De Simone, Uliana; Acerbi, Davide; Roda, Elisa

2012-01-01

There is strong epidemiological evidence that air pollution exposure (short- and long-term, i.e. < 24 hr to 3 weeks, and year/s) is related to exacerbation of cardiovascular and respiratory diseases. Data from toxicological and basic science/molecular studies, controlled animal and human exposures and human panel studies have demonstrated several mechanisms by which particle exposure may both trigger acute events as well as prompt the chronic development of cardiovascular diseases. These pollutant-mediated biological mechanisms are supporting the potential use of haematic (inflammation/coagulation/oxidative stress) markers of effects in cardio-respiratory diseases. Various examples from in vitro, in vivo and epidemiological investigations are reported, together with some novel technologies that should provide with new tools for research in these diseases and improve the knowledge about any linkage of local and systemic inflammation and clinical features of these diseases (in particular COPD), including lung function, exacerbations, disease progression, and mortality.

Evidence for a Cystic Fibrosis Enteropathy

PubMed Central

Adriaanse, Marlou P. M.; van der Sande, Linda J. T. M.; van den Neucker, Anita M.; Menheere, Paul P. C. A.; Dompeling, Edward; Buurman, Wim A.; Vreugdenhil, Anita C. E.

2015-01-01

Background Previous studies have suggested the existence of enteropathy in cystic fibrosis (CF), which may contribute to intestinal function impairment, a poor nutritional status and decline in lung function. This study evaluated enterocyte damage and intestinal inflammation in CF and studied its associations with nutritional status, CF-related morbidities such as impaired lung function and diabetes, and medication use. Methods Sixty-eight CF patients and 107 controls were studied. Levels of serum intestinal-fatty acid binding protein (I-FABP), a specific marker for enterocyte damage, were retrospectively determined. The faecal intestinal inflammation marker calprotectin was prospectively studied. Nutritional status, lung function (FEV1), exocrine pancreatic insufficiency (EPI), CF-related diabetes (CFRD) and use of proton pump inhibitors (PPI) were obtained from the medical charts. Results Serum I-FABP levels were elevated in CF patients as compared with controls (p<0.001), and correlated negatively with FEV1 predicted value in children (r-.734, p<0.05). Faecal calprotectin level was elevated in 93% of CF patients, and correlated negatively with FEV1 predicted value in adults (r-.484, p<0.05). No correlation was found between calprotectin levels in faeces and sputum. Faecal calprotectin level was significantly associated with the presence of CFRD, EPI, and PPI use. Conclusion This study demonstrated enterocyte damage and intestinal inflammation in CF patients, and provides evidence for an inverse correlation between enteropathy and lung function. The presented associations of enteropathy with important CF-related morbidities further emphasize the clinical relevance. PMID:26484665

In vitro and in vivo models of colorectal cancer: antigenotoxic activity of berries.

PubMed

Brown, Emma M; Latimer, Cheryl; Allsopp, Philip; Ternan, Nigel G; McMullan, Geoffery; McDougall, Gordon J; Stewart, Derek; Crozier, Alan; Rowland, Ian; Gill, Chris I R

2014-05-07

The etiology of colorectal cancer (CRC), a common cause of cancer-related mortality globally, has strong associations with diet. There is considerable epidemiological evidence that fruits and vegetables are associated with reduced risk of CRC. This paper reviews the extensive evidence, both from in vitro studies and animal models, that components of berry fruits can modulate biomarkers of DNA damage and that these effects may be potentially chemoprotective, given the likely role that oxidative damage plays in mutation rate and cancer risk. Human intervention trials with berries are generally consistent in indicating a capacity to significantly decrease oxidative damage to DNA, but represent limited evidence for anticarcinogenicity, relying as they do on surrogate risk markers. To understand the effects of berry consumption on colorectal cancer risk, future studies will need to be well controlled, with defined berry extracts, using suitable and clinically relevant end points and considering the importance of the gut microbiota.

Prognostic value of unrelated atypical serum immunofixation patterns during multiple myeloma therapy.

PubMed

Guimarães, Cristina; Bergantim, Rui; Ramalho, Renata; Couto, Nuno; Guimarães, João T; Trigo, Fernanda

2012-06-26

Autologous stem cell transplantation (ASCT) is the gold standard therapy for suitable multiple myeloma (MM) patients after induction with high dose therapy. To date, the evidence of a reliable marker of prognosis in these cases remains scarce. Our aim was to evaluate appearance of unrelated atypical serum immunofixation patterns (ASIPs) as a marker of prognosis in MM patients submitted to ASCT. We retrospectively analysed data from 65 patients. Interestingly, we observed that presence of ASIPs was associated with longer progression-free survival and longer overall survival. Our results suggested that presence of ASIPs could be a novel marker of good prognosis in MM patients submitted to ASCT.

[Prognostic and predictive molecular markers for urologic cancers].

PubMed

Hartmann, A; Schlomm, T; Bertz, S; Heinzelmann, J; Hölters, S; Simon, R; Stoehr, R; Junker, K

2014-04-01

Molecular prognostic factors and genetic alterations as predictive markers for cancer-specific targeted therapies are used today in the clinic for many malignancies. In recent years, many molecular markers for urogenital cancers have also been identified. However, these markers are not clinically used yet. In prostate cancer, novel next-generation sequencing methods revealed a detailed picture of the molecular changes. There is growing evidence that a combination of classical histopathological and validated molecular markers could lead to a more precise estimation of prognosis, thus, resulting in an increasing number of patients with active surveillance as a possible treatment option. In patients with urothelial carcinoma, histopathological factors but also the proliferation of the tumor, mutations in oncogenes leading to an increasing proliferation rate and changes in genes responsible for invasion and metastasis are important. In addition, gene expression profiles which could distinguish aggressive tumors with high risk of metastasis from nonmetastasizing tumors have been recently identified. In the future, this could potentially allow better selection of patients needing systemic perioperative treatment. In renal cell carcinoma, many molecular markers that are associated with metastasis and survival have been identified. Some of these markers were also validated as independent prognostic markers. Selection of patients with primarily organ-confined tumors and increased risk of metastasis for adjuvant systemic therapy could be clinically relevant in the future.

Cognitive behaviour therapy and inflammation: A systematic review of its relationship and the potential implications for the treatment of depression.

PubMed

Lopresti, Adrian L

2017-06-01

There is growing evidence confirming increased inflammation in a subset of adults with depression. The impact of this relationship has mostly been considered in biologically based interventions; however, it also has potential implications for psychological therapies. Cognitive behaviour therapy is the most commonly used psychological intervention for the treatment of depression with theories around its efficacy primarily based on psychological mechanisms. However, cognitive behaviour therapy may have an effect on, and its efficacy influenced by, physiological processes associated with depression. Accordingly, the purpose of this systematic review was to examine the relationship between cognitive behaviour therapy and inflammation. Studies examining the anti-inflammatory effects of cognitive behaviour therapy in people with depression and other medical conditions (e.g. cancer, diabetes and heart disease) were examined. In addition, the relationship between change in inflammatory markers and change in depressive symptoms following cognitive behaviour therapy, and the influence of pre-treatment inflammation on cognitive behaviour therapy treatment response were reviewed. A total of 23 studies investigating the anti-inflammatory effects of cognitive behaviour therapy were identified. In 14 of these studies, at least one reduction in an inflammatory marker was reported, increases were identified in three studies and no change was found in six studies. Three studies examined the relationship between change in inflammation and change in depressive symptoms following cognitive behaviour therapy. In two of these studies, change in depressive symptoms was associated with a change in at least one inflammatory marker. Finally, three studies examined the influence of pre-treatment inflammation on treatment outcome from cognitive behaviour therapy, and all indicated a poorer treatment response in people with higher premorbid inflammation. Preliminary evidence suggests inflammation should be considered within the context of cognitive behaviour therapy, although robust studies examining the relationship are sparse, and heterogeneity between studies and populations examined was high. The potential treatment implications of the bi-directional relationship between inflammation and cognitive behaviour therapy are discussed, and recommendations for future research are proposed.

A Genome-Wide Scan of Selective Sweeps and Association Mapping of Fruit Traits Using Microsatellite Markers in Watermelon

PubMed Central

Reddy, Umesh K.; Abburi, Lavanya; Abburi, Venkata Lakshmi; Saminathan, Thangasamy; Cantrell, Robert; Vajja, Venkata Gopinath; Reddy, Rishi; Tomason, Yan R.; Levi, Amnon; Wehner, Todd C.; Nimmakayala, Padma

2015-01-01

Our genetic diversity study uses microsatellites of known map position to estimate genome level population structure and linkage disequilibrium, and to identify genomic regions that have undergone selection during watermelon domestication and improvement. Thirty regions that showed evidence of selective sweep were scanned for the presence of candidate genes using the watermelon genome browser (www.icugi.org). We localized selective sweeps in intergenic regions, close to the promoters, and within the exons and introns of various genes. This study provided an evidence of convergent evolution for the presence of diverse ecotypes with special reference to American and European ecotypes. Our search for location of linked markers in the whole-genome draft sequence revealed that BVWS00358, a GA repeat microsatellite, is the GAGA type transcription factor located in the 5′ untranslated regions of a structure and insertion element that expresses a Cys2His2 Zinc finger motif, with presumed biological processes related to chitin response and transcriptional regulation. In addition, BVWS01708, an ATT repeat microsatellite, located in the promoter of a DTW domain-containing protein (Cla002761); and 2 other simple sequence repeats that association mapping link to fruit length and rind thickness. PMID:25425675

Characterization of the Mycobacterium tuberculosis phagosome and evidence that phagosomal maturation is inhibited

PubMed Central

1995-01-01

We have used the cryosection immunogold technique to study the composition of the Mycobacterium tuberculosis phagosome. We have used quantitative immunogold staining to determine the distribution of several known markers of the endosomal-lysosomal pathway in human monocytes after ingestion of either M. tuberculosis, Legionella pneumophila, or polystyrene beads. Compared with the other phagocytic particles studied, the M. tuberculosis phagosome exhibits delayed clearance of major histocompatibility complex (MHC) class I molecules, relatively intense staining for MHC class II molecules and the endosomal marker transferrin receptor, and relatively weak staining for the lysosomal membrane glycoproteins, CD63, LAMP-1, and LAMP-2 and the lysosomal acid protease, cathepsin D. In contrast to M. tuberculosis, the L. pneumophila phagosome rapidly clears MHC class I molecules and excludes all endosomal-lysosomal markers studied. In contrast to both live M. tuberculosis and L. pneumophila phagosomes, phagosomes containing either polystyrene beads or heat-killed M. tuberculosis stain intensely for lysosomal membrane glycoproteins and cathepsin D. These findings suggest that (a) M. tuberculosis retards the maturation of its phagosome along the endosomal-lysosomal pathway and resides in a compartment with endosomal, as opposed to lysosomal, characteristics; and (b) the intraphagosomal pathway, i.e., the pathway followed by several intracellular parasites that inhibit phagosome-lysosome fusion, is heterogeneous. PMID:7807006

Confirmation of Single-Locus Sex Determination and Female Heterogamety in Willow Based on Linkage Analysis.

PubMed

Chen, Yingnan; Wang, Tiantian; Fang, Lecheng; Li, Xiaoping; Yin, Tongming

2016-01-01

In this study, we constructed high-density genetic maps of Salix suchowensis and mapped the gender locus with an F1 pedigree. Genetic maps were separately constructed for the maternal and paternal parents by using amplified fragment length polymorphism (AFLP) markers and the pseudo-testcross strategy. The maternal map consisted of 20 linkage groups that spanned a genetic distance of 2333.3 cM; whereas the paternal map contained 21 linkage groups that covered 2260 cM. Based on the established genetic maps, it was found that the gender of willow was determined by a single locus on linkage group LG_03, and the female was the heterogametic gender. Aligned with mapped SSR markers, linkage group LG_03 was found to be associated with chromosome XV in willow. It is noteworthy that marker density in the vicinity of the gender locus was significantly higher than that expected by chance alone, which indicates severe recombination suppression around the gender locus. In conclusion, this study confirmed the findings on the single-locus sex determination and female heterogamety in willow. It also provided additional evidence that validated the previous studies, which found that different autosomes evolved into sex chromosomes between the sister genera of Salix (willow) and Populus (poplar).

Confirmation of Single-Locus Sex Determination and Female Heterogamety in Willow Based on Linkage Analysis

PubMed Central

Fang, Lecheng; Li, Xiaoping; Yin, Tongming

2016-01-01

In this study, we constructed high-density genetic maps of Salix suchowensis and mapped the gender locus with an F1 pedigree. Genetic maps were separately constructed for the maternal and paternal parents by using amplified fragment length polymorphism (AFLP) markers and the pseudo-testcross strategy. The maternal map consisted of 20 linkage groups that spanned a genetic distance of 2333.3 cM; whereas the paternal map contained 21 linkage groups that covered 2260 cM. Based on the established genetic maps, it was found that the gender of willow was determined by a single locus on linkage group LG_03, and the female was the heterogametic gender. Aligned with mapped SSR markers, linkage group LG_03 was found to be associated with chromosome XV in willow. It is noteworthy that marker density in the vicinity of the gender locus was significantly higher than that expected by chance alone, which indicates severe recombination suppression around the gender locus. In conclusion, this study confirmed the findings on the single-locus sex determination and female heterogamety in willow. It also provided additional evidence that validated the previous studies, which found that different autosomes evolved into sex chromosomes between the sister genera of Salix (willow) and Populus (poplar). PMID:26828940

Isolation and characterization of human CXCR4-positive pancreatic cells.

PubMed

Koblas, T; Zacharovová, K; Berková, Z; Mindlová, M; Girman, P; Dovolilová, E; Karasová, L; Saudek, F

2007-01-01

The existence of an adult PSC that may be used in the treatment of diabetes is still a matter of scientific debate as conclusive evidence of such a stem cell in the adult pancreas has not yet been presented. The main reason why putative PSC has not yet been identified is the lack of specific markers that may be used to isolate and purify them. In order to increase the list of potential PSC markers we have focused on the human pancreatic cells that express cell surface receptor CXCR4, a marker of stem cells derived from different adult tissues. Here we report that CXCR4-positive pancreatic cells express markers of pancreatic endocrine progenitors (neurogenin-3, nestin) and markers of pluripotent stem cells (Oct-4, Nanog, ABCG2, CD133, CD117). Upon in vitro differentiation, these cells form ILCC and produce key islet hormones including insulin. Based on our results, we assume that CXCR4 marks pancreatic endocrine progenitors and in combination with other cell surface markers may be used in the attempt to identify and isolate PSC.

ADRA2A is involved in neuro-endocrine regulation of bone resorption.

PubMed

Mlakar, Vid; Jurkovic Mlakar, Simona; Zupan, Janja; Komadina, Radko; Prezelj, Janez; Marc, Janja

2015-07-01

Adrenergic stimulation is important for osteoclast differentiation and bone resorption. Previous research shows that this happens through β2-adrenergic receptor (AR), but there are conflicting evidence on presence and role of α2A-AR in bone. The aim of this study was to investigate the presence of α2A-AR and its involvement in neuro-endocrine signalling of bone remodelling in humans. Real-time polymerase chain reaction (PCR) and immunohistochemistry were used to investigate α2A-AR receptor presence and localization in bone cells. Functionality of rs553668 and rs1800544 single nucleotide polymorphism SNPs located in α2A-AR gene was analysed by qPCR expression on bone samples and luciferase reporter assay in human osteosarcoma HOS cells. Using real-time PCR, genetic association study between rs553668 A>G and rs1800544 C>G SNPs and major bone markers was performed on 661 Slovenian patients with osteoporosis. α2A-AR is expressed in osteoblasts and lining cells but not in osteocytes. SNP rs553668 has a significant influence on α2A-AR mRNA level in human bone samples through the stability of mRNA. α2A-AR gene locus associates with important bone remodelling markers (BMD, CTX, Cathepsin K and pOC). The results of this study are providing comprehensive new evidence that α2A-AR is involved in neuro-endocrine signalling of bone turnover and development of osteoporosis. As shown by our results the neurological signalling is mediated through osteoblasts and result in bone resorption. Genetic study showed association of SNPs in α2A-AR gene locus with bone remodelling markers, identifying the individuals with higher risk of development of osteoporosis. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Metabolic profiles of biological aging in American Indians: the Strong Heart Family Study.

PubMed

Zhao, Jinying; Zhu, Yun; Uppal, Karan; Tran, ViLinh T; Yu, Tianwei; Lin, Jue; Matsuguchi, Tet; Blackburn, Elizabeth; Jones, Dean; Lee, Elisa T; Howard, Barbara V

2014-03-01

Short telomere length, a marker of biological aging, has been associated with age-related metabolic disorders. Telomere attrition induces profound metabolic dysfunction in animal models, but no study has examined the metabolome of telomeric aging in human. Here we studied 423 apparently healthy American Indians participating in the Strong Family Heart Study. Leukocyte telomere length (LTL) was measured by qPCR. Metabolites in fasting plasma were detected by untargeted LC/MS. Associations of LTL with each metabolite and their combined effects were examined using generalized estimating equation adjusting for chronological age and other aging-related factors. Multiple testing was corrected using the q-value method (q<0.05). Of the 1,364 distinct m/z features detected, nineteen metabolites in the classes of glycerophosphoethanolamines, glycerophosphocholines, glycerolipids, bile acids, isoprenoids, fatty amides, or L-carnitine ester were significantly associated with LTL, independent of chronological age and other aging-related factors. Participants with longer (top tertile) and shorter (bottom tertile) LTL were clearly separated into distinct groups using a multi-marker score comprising of all these metabolites, suggesting that these newly detected metabolites could be novel metabolic markers of biological aging. This is the first study to interrogate the human metabolome of telomeric aging. Our results provide initial evidence for a metabolic control of LTL and may reveal previously undescribed new roles of various lipids in the aging process.

Neurotransmitter systems and neurotrophic factors in autism: association study of 37 genes suggests involvement of DDC.

PubMed

Toma, Claudio; Hervás, Amaia; Balmaña, Noemí; Salgado, Marta; Maristany, Marta; Vilella, Elisabet; Aguilera, Francisco; Orejuela, Carmen; Cuscó, Ivon; Gallastegui, Fátima; Pérez-Jurado, Luis Alberto; Caballero-Andaluz, Rafaela; Diego-Otero, Yolanda de; Guzmán-Alvarez, Guadalupe; Ramos-Quiroga, Josep Antoni; Ribasés, Marta; Bayés, Mònica; Cormand, Bru

2013-09-01

Neurotransmitter systems and neurotrophic factors can be considered strong candidates for autism spectrum disorder (ASD). The serotoninergic and dopaminergic systems are involved in neurotransmission, brain maturation and cortical organization, while neurotrophic factors (NTFs) participate in neurodevelopment, neuronal survival and synapses formation. We aimed to test the contribution of these candidate pathways to autism through a case-control association study of genes selected both for their role in central nervous system functions and for pathophysiological evidences. The study sample consisted of 326 unrelated autistic patients and 350 gender-matched controls from Spain. We genotyped 369 tagSNPs to perform a case-control association study of 37 candidate genes. A significant association was obtained between the DDC gene and autism in the single-marker analysis (rs6592961, P = 0.00047). Haplotype-based analysis pinpointed a four-marker combination in this gene associated with the disorder (rs2329340C-rs2044859T-rs6592961A-rs11761683T, P = 4.988e-05). No significant results were obtained for the remaining genes after applying multiple testing corrections. However, the rs167771 marker in DRD3, associated with ASD in a previous study, displayed a nominal association in our analysis (P = 0.023). Our data suggest that common allelic variants in the DDC gene may be involved in autism susceptibility.

Medulloblastoma with myogenic and/or melanotic differentiation does not align immunohistochemically with the genetically defined molecular subgroups.

PubMed

Gupta, Kirti; Jogunoori, Swathi; Satapathy, Ayusman; Salunke, Pravin; Kumar, Narendra; Radotra, Bishan Dass; Vasishta, Rakesh Kumar

2018-05-01

The World Health Organization classification of central nervous system neoplasms (2016 update) recognizes 4 histological variants and genetically defined molecular subgroups within medulloblastoma (MB). MB with myogenic differentiation is one of the rare variants, which is usually recognized as a pattern alongside the known histological variants. Because of its rarity, less is known about its molecular landscape and importantly about its placement in the current molecular schema. We aimed to analyze this rare variant for expression of 3 immunohistochemical markers conventionally used in molecular stratification of MB. Demographic profile and imaging details with survival outcome were also analyzed. Sixty-five MB cases were molecularly stratified using immunohistochemical markers (YAP1, GAB1, β-catenin). MB with myogenic differentiation and MB cases showing variable immunoreactivity with the above 3 antibodies were further evaluated for smooth muscle actin, desmin, myogenin, and HMB45. Seven cases were categorized as MB with myogenic and/or melanotic differentiation. Age ranged from 2 to 40 years with a male-to-female ratio of 1:1.3. In 4 cases, myogenic or melanotic differentiation was evident on histology, whereas in 3, differentiation was highlighted only with muscle markers. Interestingly, all 7 cases showed variable immunoreactivity with 3 molecular markers and did not follow the conventionally accepted algorithm used for molecular stratification. Follow-up period ranged from 9 to 57 months. Overall survival revealed a varied pattern, with 3 deaths and 4 patients being alive with no evidence of disease at last follow-up. Our results provide evidence that these variants are distinct and do not align immunohistochemically with the currently recognized genetic subgroups. Copyright © 2018 Elsevier Inc. All rights reserved.

Optimal tumor sampling for immunostaining of biomarkers in breast carcinoma

PubMed Central

2011-01-01

Introduction Biomarkers, such as Estrogen Receptor, are used to determine therapy and prognosis in breast carcinoma. Immunostaining assays of biomarker expression have a high rate of inaccuracy; for example, estimates are as high as 20% for Estrogen Receptor. Biomarkers have been shown to be heterogeneously expressed in breast tumors and this heterogeneity may contribute to the inaccuracy of immunostaining assays. Currently, no evidence-based standards exist for the amount of tumor that must be sampled in order to correct for biomarker heterogeneity. The aim of this study was to determine the optimal number of 20X fields that are necessary to estimate a representative measurement of expression in a whole tissue section for selected biomarkers: ER, HER-2, AKT, ERK, S6K1, GAPDH, Cytokeratin, and MAP-Tau. Methods Two collections of whole tissue sections of breast carcinoma were immunostained for biomarkers. Expression was quantified using the Automated Quantitative Analysis (AQUA) method of quantitative immunofluorescence. Simulated sampling of various numbers of fields (ranging from one to thirty five) was performed for each marker. The optimal number was selected for each marker via resampling techniques and minimization of prediction error over an independent test set. Results The optimal number of 20X fields varied by biomarker, ranging between three to fourteen fields. More heterogeneous markers, such as MAP-Tau protein, required a larger sample of 20X fields to produce representative measurement. Conclusions The optimal number of 20X fields that must be sampled to produce a representative measurement of biomarker expression varies by marker with more heterogeneous markers requiring a larger number. The clinical implication of these findings is that breast biopsies consisting of a small number of fields may be inadequate to represent whole tumor biomarker expression for many markers. Additionally, for biomarkers newly introduced into clinical use, especially if therapeutic response is dictated by level of expression, the optimal size of tissue sample must be determined on a marker-by-marker basis. PMID:21592345

De novo assembly and characterization of leaf transcriptome for the development of functional molecular markers of the extremophile multipurpose tree species Prosopis alba

PubMed Central

2013-01-01

Background Prosopis alba (Fabaceae) is an important native tree adapted to arid and semiarid regions of north-western Argentina which is of great value as multipurpose species. Despite its importance, the genomic resources currently available for the entire Prosopis genus are still limited. Here we describe the development of a leaf transcriptome and the identification of new molecular markers that could support functional genetic studies in natural and domesticated populations of this genus. Results Next generation DNA pyrosequencing technology applied to P. alba transcripts produced a total of 1,103,231 raw reads with an average length of 421 bp. De novo assembling generated a set of 15,814 isotigs and 71,101 non-assembled sequences (singletons) with an average of 991 bp and 288 bp respectively. A total of 39,000 unique singletons were identified after clustering natural and artificial duplicates from pyrosequencing reads. Regarding the non-redundant sequences or unigenes, 22,095 out of 54,814 were successfully annotated with Gene Ontology terms. Moreover, simple sequence repeats (SSRs) and single nucleotide polymorphisms (SNPs) were searched, resulting in 5,992 and 6,236 markers, respectively, throughout the genome. For the validation of the the predicted SSR markers, a subset of 87 SSRs selected through functional annotation evidence was successfully amplified from six DNA samples of seedlings. From this analysis, 11 of these 87 SSRs were identified as polymorphic. Additionally, another set of 123 nuclear polymorphic SSRs were determined in silico, of which 50% have the probability of being effectively polymorphic. Conclusions This study generated a successful global analysis of the P. alba leaf transcriptome after bioinformatic and wet laboratory validations of RNA-Seq data. The limited set of molecular markers currently available will be significantly increased with the thousands of new markers that were identified in this study. This information will strongly contribute to genomics resources for P. alba functional analysis and genetics. Finally, it will also potentially contribute to the development of population-based genome studies in the genera. PMID:24125525

Use of near-infrared systems for investigations of hemodynamics in human in vivo bone tissue: A systematic review.

PubMed

Meertens, Robert; Casanova, Francesco; Knapp, Karen M; Thorn, Clare; Strain, William David

2018-05-04

A range of technologies using near infrared (NIR) light have shown promise at providing real time measurements of hemodynamic markers in bone tissue in vivo, an exciting prospect given existing difficulties in measuring hemodynamics in bone tissue. This systematic review aimed to evaluate the evidence for this potential use of NIR systems, establishing their potential as a research tool in this field. Major electronic databases including MEDLINE and EMBASE were searched using pre-planned search strategies with broad scope for any in vivo use of NIR technologies in human bone tissue. Following identification of studies by title and abstract screening, full text inclusion was determined by double blind assessment using predefined criteria. Full text studies for inclusion were data extracted using a predesigned proforma and quality assessed. Narrative synthesis was appropriate given the wide heterogeneity of included studies. Eighty-eight full text studies fulfilled the inclusion criteria, 57 addressing laser Doppler flowmetry (56 intra-operatively), 21 near infrared spectroscopy, and 10 photoplethysmography. The heterogeneity of the methodologies included differing hemodynamic markers, measurement protocols, anatomical locations, and research applications, making meaningful direct comparisons impossible. Further, studies were often limited by small sample sizes with potential selection biases, detection biases, and wide variability in results between participants. Despite promising potential in the use of NIR light to interrogate bone circulation, the application of NIR systems in bone requires rigorous assessment of the reproducibility of potential hemodynamic markers and further validation of these markers against alternative physiologically relevant reference standards. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1-9, 2018. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Electrocardiographic ST-Segment Depression and Exposure to Traffic‐Related Aerosols in Elderly Subjects with Coronary Artery Disease

PubMed Central

Delfino, Ralph J.; Gillen, Daniel L.; Tjoa, Thomas; Staimer, Norbert; Polidori, Andrea; Arhami, Mohammad; Sioutas, Constantinos; Longhurst, John

2011-01-01

Background Air pollutants have not been associated with ambulatory electrocardiographic evidence of ST-segment depression ≥ 1 mm (probable cardiac ischemia). We previously found that markers of primary (combustion-related) organic aerosols and gases were positively associated with circulating biomarkers of inflammation and ambulatory blood pressure in the present cohort panel study of elderly subjects with coronary artery disease. Objectives We specifically aimed to evaluate whether exposure markers of primary organic aerosols and ultrafine particles were more strongly associated with ST-segment depression of ≥ 1 mm than were secondary organic aerosols or PM2.5 (particulate matter with aerodynamic diameter ≤ 2.5 μm) mass. Methods We evaluated relations of air pollutants to ambulatory electrocardiographic evidence of cardiac ischemia over 10 days in 38 subjects without ST depression on baseline electrocardiographs. Exposures were measured outdoors in retirement communities in the Los Angeles basin, including daily size-fractionated particle mass and hourly markers of primary and secondary organic aerosols and gases. Generalized estimating equations were used to estimate odds of hourly ST-segment depression (≥ 1 mm) from hourly air pollution exposures and to estimate relative rates of daily counts of ST-segment depression from daily average exposures, controlling for potential confounders. Results We found significant positive associations of hourly ST-segment depression with markers of combustion-related aerosols and gases averaged 1-hr through 3–4 days, but not secondary (photochemically aged) organic aerosols or ozone. The odds ratio per interquartile increase in 2-day average primary organic carbon (5.2 μg/m3) was 15.4 (95% confidence interval, 3.5–68.2). Daily counts of ST-segment depression were consistently associated with primary combustion markers and 2-day average quasi-ultrafine particles < 0.25 μm. Conclusions Results suggest that exposure to quasi-ultrafine particles and combustion-related pollutants (predominantly from traffic) increase the risk of myocardial ischemia, coherent with our previous findings for systemic inflammation and blood pressure. PMID:20965803

Criteria for evaluating evidence on public health interventions.

PubMed

Rychetnik, L; Frommer, M; Hawe, P; Shiell, A

2002-02-01

Public health interventions tend to be complex, programmatic, and context dependent. The evidence for their effectiveness must be sufficiently comprehensive to encompass that complexity. This paper asks whether and to what extent evaluative research on public health interventions can be adequately appraised by applying well established criteria for judging the quality of evidence in clinical practice. It is adduced that these criteria are useful in evaluating some aspects of evidence. However, there are other important aspects of evidence on public health interventions that are not covered by the established criteria. The evaluation of evidence must distinguish between the fidelity of the evaluation process in detecting the success or failure of an intervention, and the success or failure of the intervention itself. Moreover, if an intervention is unsuccessful, the evidence should help to determine whether the intervention was inherently faulty (that is, failure of intervention concept or theory), or just badly delivered (failure of implementation). Furthermore, proper interpretation of the evidence depends upon the availability of descriptive information on the intervention and its context, so that the transferability of the evidence can be determined. Study design alone is an inadequate marker of evidence quality in public health intervention evaluation.

Examining markers in 8q24 to explain differences in evidence for association with cleft lip with/without cleft palate between Asians and Europeans

PubMed Central

Murray, Tanda; Taub, Margaret A.; Ruczinski, Ingo; Scott, Alan F.; Hetmanski, Jacqueline B.; Schwender, Holger; Patel, Poorav; Zhang, Tian Xiao; Munger, Ronald G.; Wilcox, Allen J.; Ye, Xiaoqian; Wang, Hong; Wu, Tao; Wu-Chou, Yah Huei; Shi, Bing; Jee, Sun Ha; Chong, Samuel; Yeow, Vincent; Murray, Jeffrey C.; Marazita, Mary L.; Beaty, Terri H.

2013-01-01

In a recent genome wide association study (GWAS) from an international consortium, evidence of linkage and association in chr8q24 was much stronger among non-syndromic cleft lip/palate (CL/P) case-parent trios of European ancestry than among trios of Asian ancestry. We examined marker information content and haplotype diversity across 13 recruitment sites (from Europe, USA and Asia) separately, and conducted principal components analysis (PCA) on parents. As expected, PCA revealed large genetic distances between Europeans and Asians, and a north-south cline from Korea to Singapore in Asia, with Filipino parents forming a somewhat distinct Southeast Asian cluster. Hierarchical clustering of SNP heterozygosity revealed two major clades consistent with PCA results. All genotyped SNPs giving p<10−6 in the allelic TDT showed higher heterozygosity in Europeans than Asians. On average, European ancestry parents had higher haplotype diversity than Asians. Imputing additional variants across chr8q24 increased the strength of statistical evidence among Europeans and also revealed a significant signal among Asians (although it did not reach genome-wide significance). Tests for SNP-population interaction were negative, indicating the lack of strong signal for 8q24 in families of Asian ancestry was not due to any distinct genetic effect, but could simply reflect low power due to lower allele frequencies in Asians. PMID:22508319

Peripheral T-Cell Lymphoma with Aberrant Expression of CD19, CD20, and CD79a: Case Report and Literature Review

PubMed Central

Matnani, Rahul G.; Stewart, Rachel L.; Pulliam, Joseph; Jennings, Chester D.; Kesler, Melissa

2013-01-01

A case of lymphoma of T-cell derivation with aberrant expression of three B-cell lineage markers (CD19, CD20, and CD79a), which was diagnosed on a left axillary excision, is described. Immunohistochemical studies and flow cytometry analysis demonstrated neoplastic cells expressing CD3, CD19, CD20, and CD79a with absence of CD4, CD8, CD10, CD30, CD34, CD56, CD68, TDT, MPO, PAX-5, and surface immunoglobulin. Gene rearrangement studies performed on paraffin blocks demonstrated monoclonal T-cell receptor gamma chain rearrangement with no evidence of clonal heavy chain rearrangement. The neoplastic cells were negative for Epstein-Barr virus (EBV) or Human Herpes Virus 8 (HHV-8). At the time of diagnosis, the PET scan demonstrated hypermetabolic neoplastic cells involving the left axilla, bilateral internal jugular areas, mediastinum, right hilum, bilateral lungs, and spleen. However, bone marrow biopsy performed for hemolytic anemia revealed normocellular bone marrow with trilineage maturation. The patient had no evidence of immunodeficiency or infection with EBV or HHV-8. This is the first reported case of a mature T-cell lymphoma with aberrant expression of three B-cell lineage markers. The current report also highlights the need for molecular gene rearrangement studies to determine the precise lineage of ambiguous neoplastic clones. PMID:24066244

Interpopulation hybridization results in widespread viability selection across the genome in Tigriopus californicus

PubMed Central

2011-01-01

Background Genetic interactions within hybrids influence their overall fitness. Understanding the details of these interactions can improve our understanding of speciation. One experimental approach is to investigate deviations from Mendelian expectations (segregation distortion) in the inheritance of mapped genetic markers. In this study, we used the copepod Tigriopus californicus, a species which exhibits high genetic divergence between populations and a general pattern of reduced fitness in F2 interpopulation hybrids. Previous studies have implicated both nuclear-cytoplasmic and nuclear-nuclear interactions in causing this fitness reduction. We identified and mapped population-diagnostic single nucleotide polymorphisms (SNPs) and used these to examine segregation distortion across the genome within F2 hybrids. Results We generated a linkage map which included 45 newly elucidated SNPs and 8 population-diagnostic microsatellites used in previous studies. The map, the first available for the Copepoda, was estimated to cover 75% of the genome and included markers on all 12 T. californicus chromosomes. We observed little segregation distortion in newly hatched F2 hybrid larvae (fewer than 10% of markers at p < 0.05), but strikingly higher distortion in F2 hybrid adult males (45% of markers at p < 0.05). Hence, segregation distortion was primarily caused by selection against particular genetic combinations which acted between hatching and maturity. Distorted markers were not distributed randomly across the genome but clustered on particular chromosomes. In contrast to other studies in this species we found little evidence for cytonuclear coadaptation. Instead, different linkage groups exhibited markedly different patterns of distortion, which appear to have been influenced by nuclear-nuclear epistatic interactions and may also reflect genetic load carried within the parental lines. Conclusion Adult male F2 hybrids between two populations of T. californius exhibit dramatic segregation distortion across the genome. Distorted loci are clustered within specific linkage groups, and the direction of distortion differs between chromosomes. This segregation distortion is due to selection acting between hatching and adulthood. PMID:21639918

The contribution of molecular epidemiology to the identification of human carcinogens: current status and future perspectives.

PubMed

Boffetta, P; Islami, F

2013-04-01

The use of biological-based markers of exposure, intermediate effect, outcome, and susceptibility has become standard practice in cancer epidemiology, which has contributed to identification of several carcinogenic agents. Nevertheless, with the exception of biological agents, this contribution, in terms of providing sufficiently strong evidence as required by the International Agency for Research on Cancer (IARC) monographs, has been modest. We discuss the overall contribution of molecular epidemiology to identification of carcinogens, with focus on IARC monographs. For many carcinogens, valid biological markers of exposure and mechanisms of actions are not available. Molecular markers are usually assessed in single biological samples, which may not represent the actual exposure or biological events related to carcinogens. The contribution of molecular epidemiology to identification of carcinogens has mainly been limited to the carcinogens acting through a genotoxic mechanism, i.e. when carcinogens induce DNA damage. A number of factors, including certain hormones and overweight/obesity, may show carcinogenic effects through nongenotoxic pathways, for which mechanisms of carcinogenicity are not well identified and their biomarkers are sparse. Longitudinal assessment of biomarkers may provide more informative data in molecular epidemiology studies. For many carcinogens and mechanistic pathways, in particular nongenotoxic carcinogenicity, valid biological markers still need to be identified.

Integral Phylogenomic Approach over Ilex L. Species from Southern South America

PubMed Central

Cascales, Jimena; Bracco, Mariana; Garberoglio, Mariana J.; Poggio, Lidia; Gottlieb, Alexandra M.

2017-01-01

The use of molecular markers with inadequate variation levels has resulted in poorly resolved phylogenetic relationships within Ilex. Focusing on southern South American and Asian species, we aimed at contributing informative plastid markers. Also, we intended to gain insights into the nature of morphological and physiological characters used to identify species. We obtained the chloroplast genomes of I. paraguariensis and I. dumosa, and combined these with all the congeneric plastomes currently available to accomplish interspecific comparisons and multilocus analyses. We selected seven introns and nine IGSs as variable non-coding markers that were used in phylogenomic analyses. Eight extra IGSs were proposed as candidate markers. Southern South American species formed one lineage, except for I. paraguariensis, I. dumosa and I. argentina, which occupied intermediate positions among sampled taxa; Euroasiatic species formed two lineages. Some concordant relationships were retrieved from nuclear sequence data. We also conducted integral analyses, involving a supernetwork of molecular data, and a simultaneous analysis of quantitative and qualitative morphological and phytochemical characters, together with molecular data. The total evidence tree was used to study the evolution of non-molecular data, evidencing fifteen non-ambiguous synapomorphic character states and consolidating the relationships among southern South American species. More South American representatives should be incorporated to elucidate their origin. PMID:29165335

Global Population Genetic Analysis of Aspergillus fumigatus

PubMed Central

Ashu, Eta Ebasi; Hagen, Ferry; Chowdhary, Anuradha

2017-01-01

ABSTRACT Aspergillus fumigatus is a ubiquitous opportunistic fungal pathogen capable of causing invasive aspergillosis, a globally distributed disease with a mortality rate of up to 90% in high-risk populations. Effective control and prevention of this disease require a thorough understanding of its epidemiology. However, despite significant efforts, the global molecular epidemiology of A. fumigatus remains poorly understood. In this study, we analyzed 2,026 A. fumigatus isolates from 13 countries in four continents using nine highly polymorphic microsatellite markers. Genetic cluster analyses suggest that our global sample of A. fumigatus isolates belonged to eight genetic clusters, with seven of the eight clusters showing broad geographic distributions. We found common signatures of sexual recombination within individual genetic clusters and clear evidence of hybridization between several clusters. Limited but statistically significant genetic differentiations were found among geographic and ecological populations. However, there was abundant evidence for gene flow at the local, regional, and global scales. Interestingly, the triazole-susceptible and triazole-resistant populations showed different population structures, consistent with antifungal drug pressure playing a significant role in local adaptation. Our results suggest that global populations of A. fumigatus are shaped by historical differentiation, contemporary gene flow, sexual reproduction, and the localized antifungal drug selection that is driving clonal expansion of genotypes resistant to multiple triazole drugs. IMPORTANCE The genetic diversity and geographic structure of the human fungal pathogen A. fumigatus have been the subject of many studies. However, most previous studies had relatively limited sample ranges and sizes and/or used genetic markers with low-level polymorphisms. In this paper, we characterize a global collection of strains of A. fumigatus using a panel of 9 highly polymorphic microsatellite markers. Using these markers, we analyze 2,026 isolates, which is ~3 times the number of isolates reported so far in previous studies. Our analyses suggest that A. fumigatus contains historically differentiated genetic populations but that its evolution is significantly impacted by contemporary forces such as widespread gene flow and local antifungal drug pressure. In the wake of a global rise in resistance to azoles in fungal pathogens, our findings should aid in developing management strategies to mitigate current increases to azole resistance. PMID:28168221

The response of Isidorella newcombi to copper exposure: Using an integrated biological framework to interpret transcriptomic responses from RNA-seq analysis.

PubMed

Ubrihien, Rodney P; Ezaz, Tariq; Taylor, Anne M; Stevens, Mark M; Krikowa, Frank; Foster, Simon; Maher, William A

2017-04-01

This study describes the transcriptomic response of the Australian endemic freshwater gastropod Isidorella newcombi exposed to 80±1μg/L of copper for 3days. Analysis of copper tissue concentration, lysosomal membrane destabilisation and RNA-seq were conducted. Copper tissue concentrations confirmed that copper was bioaccumulated by the snails. Increased lysosomal membrane destabilisation in the copper-exposed snails indicated that the snails were stressed as a result of the exposure. Both copper tissue concentrations and lysosomal destabilisation were significantly greater in snails exposed to copper. In order to interpret the RNA-seq data from an ecotoxicological perspective an integrated biological response model was developed that grouped transcriptomic responses into those associated with copper transport and storage, survival mechanisms and cell death. A conceptual model of expected transcriptomic changes resulting from the copper exposure was developed as a basis to assess transcriptomic responses. Transcriptomic changes were evident at all the three levels of the integrated biological response model. Despite lacking statistical significance, increased expression of the gene encoding copper transporting ATPase provided an indication of increased internal transport of copper. Increased expression of genes associated with endocytosis are associated with increased transport of copper to the lysosome for storage in a detoxified form. Survival mechanisms included metabolic depression and processes associated with cellular repair and recycling. There was transcriptomic evidence of increased cell death by apoptosis in the copper-exposed organisms. Increased apoptosis is supported by the increase in lysosomal membrane destabilisation in the copper-exposed snails. Transcriptomic changes relating to apoptosis, phagocytosis, protein degradation and the lysosome were evident and these processes can be linked to the degradation of post-apoptotic debris. The study identified contaminant specific transcriptomic markers as well as markers of general stress. From an ecotoxicological perspective, the use of a framework to group transcriptomic responses into those associated with copper transport, survival and cell death assisted with the complex process of interpretation of RNA-seq data. The broad adoption of such a framework in ecotoxicology studies would assist in comparison between studies and the identification of reliable transcriptomic markers of contaminant exposure and response. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization of the Murine Myeloid Precursor Cell Line MuMac-E8

PubMed Central

Fricke, Stephan; Riemschneider, Sina; Kohlschmidt, Janine; Hilger, Nadja; Fueldner, Christiane; Knauer, Jens; Sack, Ulrich; Emmrich, Frank; Lehmann, Jörg

2014-01-01

Starting point for the present work was the assumption that the cell line MuMac-E8 represents a murine cell population with stem cell properties. Preliminary studies already pointed to the expression of stem-cell associated markers and a self-regenerative potential of the cells. The cell line MuMac-E8 should be examined for their differential stage within stem cell hierarchy. MuMac-E8 cells were derived from a chimeric mouse model of arthritis. It could be shown that MuMac-E8 cells express mRNA of some genes associated with pluripotent stem cells (Nanog, Nucleostemin), of genes for hematopoietic markers (EPCR, Sca-1, CD11b, CD45), for the mesenchymal marker CD105 and of genes for the neural markers Pax-6 and Ezrin. In methylcellulose and May-Grünwald-Giemsa staining, hematopoietic colonies were obtained but the hematopoietic system of lethally irradiated mice could not be rescued. Osteogenic differentiation was not detectable. Thus, it became evident that MuMac-E8 represents not a stem cell line. However, MuMac-E8 cells expressed several myeloid surface markers (i.e. CD11b, F4/80, CD14, CD64), showed phagocytosis and is capable of producing nitric oxide. Thus, this cell line seems to be arrested an advanced stage of myeloid differentiation. Adherence data measured by impedance-based real-time cell analysis together with cell morphology data suggested that MuMac-E8 represents a new macrophage precursor cell line exhibiting weak adherence. This cell line is suitable as an in-vitro model for testing of macrophage functions. Moreover, it might be also useful for differentiation or reprogramming studies. PMID:25546418

Effect of Psyllium Fiber Supplementation on C-Reactive Protein: The Trial to Reduce Inflammatory Markers (TRIM)

PubMed Central

King, Dana E.; Mainous, Arch G.; Egan, Brent M.; Woolson, Robert F.; Geesey, Mark E.

2008-01-01

PURPOSE Recent evidence supports a significant association between the intake of dietary fiber and levels of inflammatory markers. The objective of this study was to determine whether daily fiber supplementation would reduce levels of inflammatory markers. METHODS This study was a prospective randomized controlled trial at a single university medical center. Participants were overweight or obese adults with no history of heart disease. The intervention was psyllium supplementation at either 7 or 14 g/d for 3 months compared with no supplements in a control group. The main outcome measure was change in level of high-sensitivity C-reactive protein (hsCRP) concentration; secondary outcomes included changes in interleukin-6 (IL-6) levels, fibrinogen levels, and white blood cell (WBC) count. Protocol completers attended at least 2 visits and took more than 75% of the prescribed fiber dose. RESULTS In this intent-to-treat analysis (n = 158), there were no significant differences between either of the 2 treatment groups and the control group in the amount of change in CRP, fibrinogen, or IL-6 levels or in WBC count (P>.05). In the analysis of protocol completers (n = 132), there also were no significant differences between the groups except for a small decrease in fibrinogen level in the high-fiber group (−6 mg/dL [−0.18 μmol/L] compared with 13 mg/dL [0.38 μmol/L] in the control group, P<.05). CONCLUSION Psyllium fiber supplementation did not significantly reduce CRP levels in overweight or obese individuals in this trial, and changes in other markers were not consistent. Further research is needed to determine whether other fibers or nutrients can reduce inflammatory markers. PMID:18332401

Genetic Lineage Tracing of Non-Myocyte Population by Dual Recombinases.

PubMed

Li, Yan; He, Lingjuan; Huang, Xiuzhen; Issa Bhaloo, Shirin; Zhao, Huan; Zhang, Shaohua; Pu, Wenjuan; Tian, Xueying; Li, Yi; Liu, Qiaozhen; Yu, Wei; Zhang, Libo; Liu, Xiuxiu; Liu, Kuo; Tang, Juan; Zhang, Hui; Cai, Dongqing; Adams, Ralf H; Xu, Qingbo; Lui, Kathy O; Zhou, Bin

2018-04-26

Background -Whether the adult mammalian heart harbors cardiac stem cells (CSCs) for regeneration of cardiomyocytes is an important yet contentious topic in the field of cardiovascular regeneration. The putative myocyte stem cell populations recognized without specific cell markers such as the cardiosphere-derived cells or with markers such as Sca1 + , Bmi1 + , Isl1 + or Abcg2 + CSCs have been reported. Moreover, it remains unclear whether putative CSCs with unknown or unidentified markers exist and give rise to de novo cardiomyocytes in the adult heart. Methods -To address this question without relying on a particular stem cell marker, we developed a new genetic lineage tracing system to label all non-myocyte populations that contain putative CSCs. Using dual lineage tracing system, we assessed if non-myocytes generated any new myocytes during embryonic development, adult homeostasis and after myocardial infarction. Skeletal muscle was also examined after injury for internal control of new myocytes generation from non-myocytes. Results -By this stem cell marker-free and dual recombinases-mediated cell tracking approach, our fate mapping data show that new myocytes arise from non-myocytes in the embryonic heart, but not in the adult heart during homeostasis or after myocardial infarction. As positive control, our lineage tracing system detected new myocytes derived from non-myocytes in the skeletal muscle after injury. Conclusions -This study provides in vivo genetic evidence for non-myocyte to myocyte conversion in embryonic but not adult heart, arguing again the myogenic potential of putative stem cell populations for cardiac regeneration in the adult stage. This study also provides a new genetic strategy to identify endogenous stem cells, if any, in other organ systems for tissue repair and regeneration.

Oxidative stress-induced cognitive impairment in obesity can be reversed by vitamin D administration in rats.

PubMed

Hajiluian, Ghazaleh; Abbasalizad Farhangi, Mahdieh; Nameni, Ghazaleh; Shahabi, Parviz; Megari-Abbasi, Mehran

2017-07-06

There is evidence that obesity leads to cognitive impairments via several markers of oxidative stress including glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase and malondialdehyde (MDA) in the hippocampus. Increased inflammatory markers in the brain have obesity triggering effects. In the current study we aimed to investigate the effects of vitamin D on cognitive function, nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α concentration and markers of oxidative stress in the hippocampus of high-fat diet-induced obese rats. Forty male Wistar rats were divided into two groups: control diet (CD) and high-fat diet (HFD) for 16 weeks; then each group subdivided into two groups including: CD, CD + vitamin D, HFD and HFD + vitamin D. Vitamin D was administered at 500 IU/kg dosage for 5 weeks. Four weeks after supplementation, Morris water maze test was performed. NF-κB and TNF-α concentration in the hippocampus were determined using ELISA kits. Moreover, oxidative stress markers in the hippocampus including GPx, SOD, MDA and CAT concentrations were measured by spectrophotometry methods. HFD significantly increased TNF-α (P = 0.04) and NF-κB (P = 0.01) concentrations in the hippocampus compared with CD. Vitamin D treatment led to a significant reduction in hippocampus NF-κB concentrations in HFD + vitamin D group (P = 0.001); however, vitamin D had no effect on TNF-α concentrations. Moreover, HFD significantly induced oxidative stress by reducing GPx, SOD and increasing MDA concentrations in the hippocampus. Vitamin D supplementation in HFD group also significantly increased GPx, SOD and reduced MDA concentrations. Vitamin D improved hippocampus oxidative stress and inflammatory markers in HFD-induced obese rats and improved cognitive performance. Further studies are needed to better clarify the underlying mechanisms.

Appropriateness of tumor marker request: a case of study

PubMed Central

Trevisiol, Chiara; Fabricio, Aline S. C.

2017-01-01

Appropriateness is crucial to provide efficient and high-quality health services at affordable costs. Laboratory medicine is a sector of special interest for the investigation of inappropriateness, due to the high rate of technological innovation and its pivotal role in many diseases and clinical settings. Some subjective aspects related to either the patient or physician seem to have a major role on inappropriateness rates. Given the psychological impact of cancer on both patients and physicians, tumor markers represent a case of study for appropriateness. The assessment of inappropriateness of laboratory tests has been focused mainly on ordering patterns. Appropriateness can barely be appraised by matching the requested test with the clinical problem because clinical information on the test requisition form is usually inadequate. Monitoring inappropriateness through individual clinical information may be feasible in inpatient (clinical data are available), while an indirect approach should be used for outpatients. To estimate inappropriateness in outpatients our group developed innovative models based on comparison between the actually ordered and expected requests of tumor marker, calculated according to recommendations of clinical practice guidelines (CPGs) applied to figures of cancer prevalence. The implementation of the model at national scale in Italy led to recognize a very high rate of overordering of tumor markers. The model was further focused by a dedicated algorithm to be adapted to different clinical conditions or organizational settings by applying performance indicators to cohort-wide structured information in electronic health records (EHRs). With this novel approach, we showed that inappropriateness is multifaceted even within the specific category of tumour markers. The model was effective in identifying both over- and underordering. Implementation of evidence based information and monitoring their impact on the clinical practice are parts of the same, multistage, process aimed at the progressive improvement of health care. PMID:28758100

Cancer stem cells (CSCs), cervical CSCs and targeted therapies

PubMed Central

Huang, Ruixia; Rofstad, Einar K.

2017-01-01

Accumulating evidence has shown that cancer stem cells (CSCs) have a tumour-initiating capacity and play crucial roles in tumour metastasis, relapse and chemo/radio-resistance. As tumour propagation initiators, CSCs are considered to be promising targets for obtaining a better therapeutic outcome. Cervical carcinoma is the most common gynaecological malignancy and has a high cancer mortality rate among females. As a result, the investigation of cervical cancer stem cells (CCSCs) is of great value. However, the numbers of cancer cells and corresponding CSCs in malignancy are dynamically balanced, and CSCs may reside in the CSC niche, about which little is known to date. Therefore, due to their complicated molecular phenotypes and biological behaviours, it remains challenging to obtain “purified” CSCs and continuously culture CSCs for further in vitro studies without the cells losing their stem properties. At present, CSC-related markers and functional assays are used to purify, identify and therapeutically target CSCs both in vitro and in vivo. Nevertheless, CSC-related markers are not universal to all tumour types, although some markers may be valid in multiple tumour types. Additionally, functional identifications based on CSC-specific properties are usually limited in in vivo studies. Furthermore, an optimal method for identifying potential CCSCs in CCSC studies has not been previously published, and these techniques are currently of great importance. This article updates our knowledge on CSCs and CCSCs, reviews potential stem cell markers and functional assays for identifying CCSCs, and describes the potential of targeting CCSCs in the treatment of cervical carcinoma. PMID:27343550

Serum S100B Represents a New Biomarker for Mood Disorders

PubMed Central

Schroeter, Matthias L.; Sacher, Julia; Steiner, Johann; Schoenknecht, Peter; Mueller, Karsten

2013-01-01

Recently, mood disorders have been discussed to be characterized by glial pathology. The protein S100B, a growth and differentiation factor, is located in, and may actively be released by astro- and oligodendrocytes. This protein is easily assessed in human serum and provides a useful parameter for glial activation or injury. Here, we review studies investigating the glial marker S100B in serum of patients with mood disorders. Studies consistently show that S100B is elevated in mood disorders; more strongly in major depressive than bipolar disorder. Consistent with the glial hypothesis of mood disorders, serum S100B levels interact with age with higher levels in elderly depressed subjects. Successful antidepressive treatment has been associated with serum S100B reduction in major depression, whereas there is no evidence of treatment effects in mania. In contrast to the glial marker S100B, the neuronal marker protein neuron-specific enolase is unaltered in mood disorders. Recently, serum S100B has been linked to specific imaging parameters in the human white matter suggesting a role for S100B as an oligodendrocytic marker protein. In sum, serum S100B can be regarded as a promising in vivo biomarker for mood disorders deepening the understanding of the pathogenesis and plasticity-changes in these disorders. Future longitudinal studies combining serum S100B with other cell-specific serum parameters and multimodal imaging are warranted to further explore this serum protein in the development, monitoring and treatment of mood disorders. PMID:23701298

Absence of detectable mitochondrial recombination in Paramecium.

PubMed

Adoutte, A; Knowles, J K; Sainsard-Chanet, A

1979-12-01

An extensive search for recombination between mitochondrial markers was carried out in Paramecium tetraurelia. Thirty-two combinations, altogether involving 24 different markers, were studied. The markers belonged to the three main categories of mitochondrial mutations presently available in this organism, (a) Spontaneous or UV-induced antibiotic resistance mutations, most probably affecting mitochondrial ribosomes, (b) nitrosoguanidine-induced antibiotic resistance markers displaying thermosensitivity or slow growth, enabling easy selection of possible wild-type recombinants, and (c) mitochondrial partial suppressors of a nuclear gene, probably corresponding to molecular alterations distinct from the preceding two categories. In addition, different genetic configurations were analyzed (i.e., mutant X mutant, double-mutant X wild-type, etc.).--None of the combinations yielded any evidence for the occurrence of recombined genomes despite the fact that: (1) all of them were studied on a large scale involving the screening of at least several thousand mitochondrial genomes (often several millions), (2) in many of them the detection level was sufficiently high to enable the isolation of spontaneous mutants in control cells, and (3) in several of them, reconstitution experiments carried out in parallel show that the conditions were fully adequate to detect recombinant genotypes. The results are in marked contrast with those obtained on the few other organisms in which mitochondrial recombination has been studied, particularly Saccharomyces cerevisiae, in which mitochondrial recombination is intense.--The most likely basis for the various manifestations of mitochondrial genetic autonomy in Paramecium, described in this as well as in previous publications, is that the chondriome of this organism is made up of thousands of structurally discrete, noninteracting units.

Salivary Markers of Inflammation in Response to Acute Stress

PubMed Central

Slavish, Danica C.; Graham-Engeland, Jennifer E.; Smyth, Joshua M.; Engeland, Christopher G.

2014-01-01

There is burgeoning interest in the ability to detect inflammatory markers in response to stress within naturally occurring social contexts and/or across multiple time points per day within individuals. Salivary collection is a less invasive process than current methods of blood collection and enables intensive naturalistic methodologies, such as those involving extensive repeated measures per day over time. Yet the reliability and validity of saliva-based to blood-based inflammatory biomarkers in response to stress remains unclear. We review and synthesize the published studies that have examined salivary markers of inflammation following exposure to an acute laboratory stressor. Results from each study are reviewed by analyte (IL-1β, TNF-α, IL-6, IL-2, IL-4, IL-10, IL-12, CRP) and stress type (social-cognitive and exercise-physical), after which methodological issues and limitations are addressed. Although the literature is limited, several inflammatory markers (including IL-1β, TNF-α, and IL-6) have been reliably determined from saliva and have increased significantly in response to stress across multiple studies, with effect sizes ranging from very small to very large. Although CRP from saliva has been associated with CRP in circulating blood more consistently than other biomarkers have been associated with their counterparts in blood, evidence demonstrating it reliably responds to acute stress is absent. Although the current literature is presently too limited to allow broad assertion that inflammatory biomarkers determined from saliva are valuable for examining acute stress responses, this review suggests that specific targets may be valid and highlights specific areas of need for future research. PMID:25205395

Birth Characteristics and Childhood Leukemia Risk: Correlations With Genetic Markers.

PubMed

Kennedy, Amy E; Kamdar, Kala Y; Lupo, Philip J; Okcu, Mehmet F; Scheurer, Michael E; Dorak, Mehmet T

2015-07-01

Birth characteristics such as birth order, birth weight, birth defects, and Down syndrome showed some of the first risk associations with childhood leukemia. Examinations of correlations between birth characteristics and leukemia risk markers have been limited to birth weight-related genetic polymorphisms. We integrated information on nongenetic and genetic markers by evaluating the relationship of birth characteristics, genetic markers for childhood acute lymphoblastic leukemia (ALL) susceptibility, and ALL risk together. The multiethnic study consisted of cases with childhood ALL (n=161) and healthy controls (n=261). Birth characteristic data were collected through questionnaires, and genotyping was achieved by TaqMan SNP Genotyping Assays. We observed risk associations for birth weight over 4000 g (odds ratios [OR]=1.93; 95% confidence interval [CI], 1.16-3.19), birth length (OR=1.18 per inch; 95% CI, 1.01-1.38), and with gestational age (OR=1.10 per week; 95% CI, 1.00-1.21). Only the HFE tag single-nucleotide polymorphism (SNP) rs9366637 showed an inverse correlation with a birth characteristic, gestational age, with a gene-dosage effect (P=0.005), and in interaction with a transferrin receptor rs3817672 genotype (Pinteraction=0.05). This correlation translated into a strong association for rs9366637 with preterm birth (OR=5.0; 95% CI, 1.19-20.9). Our study provides evidence for the involvement of prenatal events in the development of childhood ALL. The inverse correlation of rs9366637 with gestational age has implications on the design of HFE association studies in birth weight and childhood conditions using full-term newborns as controls.

Risk factors and seroprevalence of markers for hepatitis A, B and C in persons subject to homelessness in inner Sydney.

PubMed

Poulos, Roslyn; Ferson, Mark; Orr, Karen; Lucy, Adrienne; Botham, Susan; McCarthy, Michele; Stern, Jerome; Dixon, Julie; Murray, Carolyn; Polis, Suzanne

2007-06-01

To determine the seroprevalence of hepatitis A, B and C and the prevalence of risk factors for blood-borne infections in persons subject to homelessness attending a medical clinic in inner Sydney. During 2003-05, 201 clients were enrolled in a prospective study to determine the acceptance, completion rates and immunogenicity of the standard vaccination schedule for hepatitis A and B. On enrolment, clients completed a risk factor assessment questionnaire and undertook pre-vaccination serological screening for hepatitis A, B and C. Forty-five per cent (85/188) of clients were positive for anti-HCV antibodies; 32% (60/189) showed evidence of past infection with HBV (anti-HBc); and 48% (89/189) were positive for anti-HAV antibodies. It was not uncommon for clients to have multiple markers of hepatitis. A past history of injecting drug use was significantly associated with markers for hepatitis B and C; age predicted presence of anti-HAV. A verbal history of infection appeared more reliable for hepatitis C, but considerably less so for hepatitis A and B. Persons subject to homelessness are at risk of blood-borne infection. The seroprevalence of markers for hepatitis B and C are higher than in the general population. Despite the high proportion of clients with serological markers for hepatitis A and B, at least 69% of clients could potentially benefit from hepatitis A and/or B vaccination.

Transcriptomic Analyses Reveal Differential Gene Expression of Immune and Cell Death Pathways in the Brains of Mice Infected with West Nile Virus and Chikungunya Virus

PubMed Central

Lim, Stephanie M.; van den Ham, Henk-Jan; Oduber, Minoushka; Martina, Eurydice; Zaaraoui-Boutahar, Fatiha; Roose, Jeroen M.; van IJcken, Wilfred F. J.; Osterhaus, Albert D. M. E.; Andeweg, Arno C.; Koraka, Penelope; Martina, Byron E. E.

2017-01-01

West Nile virus (WNV) and chikungunya virus (CHIKV) are arboviruses that are constantly (re-)emerging and expanding their territory. Both viruses often cause a mild form of disease, but severe forms of the disease can consist of neurological symptoms, most often observed in the elderly and young children, respectively, for which the mechanisms are poorly understood. To further elucidate the mechanisms responsible for end-stage WNV and CHIKV neuroinvasive disease, we used transcriptomics to compare the induction of effector pathways in the brain during the early and late stage of disease in young mice. In addition to the more commonly described cell death pathways such as apoptosis and autophagy, we also found evidence for the differential expression of pyroptosis and necroptosis cell death markers during both WNV and CHIKV neuroinvasive disease. In contrast, no evidence of cell dysfunction was observed, indicating that cell death may be the most important mechanism of disease. Interestingly, there was overlap when comparing immune markers involved in neuroinvasive disease to those seen in neurodegenerative diseases. Nonetheless, further validation studies are needed to determine the activation and involvement of these effector pathways at the end stage of disease. Furthermore, evidence for a strong inflammatory response was found in mice infected with WNV and CHIKV. The transcriptomics profile measured in mice with WNV and CHIKV neuroinvasive disease in our study showed strong overlap with the mRNA profile described in the literature for other viral neuroinvasive diseases. More studies are warranted to decipher the role of cell inflammation and cell death in viral neuroinvasive disease and whether common mechanisms are active in both neurodegenerative and brain infectious diseases. PMID:28861067

Transcriptomic Analyses Reveal Differential Gene Expression of Immune and Cell Death Pathways in the Brains of Mice Infected with West Nile Virus and Chikungunya Virus.

PubMed

Lim, Stephanie M; van den Ham, Henk-Jan; Oduber, Minoushka; Martina, Eurydice; Zaaraoui-Boutahar, Fatiha; Roose, Jeroen M; van IJcken, Wilfred F J; Osterhaus, Albert D M E; Andeweg, Arno C; Koraka, Penelope; Martina, Byron E E

2017-01-01

West Nile virus (WNV) and chikungunya virus (CHIKV) are arboviruses that are constantly (re-)emerging and expanding their territory. Both viruses often cause a mild form of disease, but severe forms of the disease can consist of neurological symptoms, most often observed in the elderly and young children, respectively, for which the mechanisms are poorly understood. To further elucidate the mechanisms responsible for end-stage WNV and CHIKV neuroinvasive disease, we used transcriptomics to compare the induction of effector pathways in the brain during the early and late stage of disease in young mice. In addition to the more commonly described cell death pathways such as apoptosis and autophagy, we also found evidence for the differential expression of pyroptosis and necroptosis cell death markers during both WNV and CHIKV neuroinvasive disease. In contrast, no evidence of cell dysfunction was observed, indicating that cell death may be the most important mechanism of disease. Interestingly, there was overlap when comparing immune markers involved in neuroinvasive disease to those seen in neurodegenerative diseases. Nonetheless, further validation studies are needed to determine the activation and involvement of these effector pathways at the end stage of disease. Furthermore, evidence for a strong inflammatory response was found in mice infected with WNV and CHIKV. The transcriptomics profile measured in mice with WNV and CHIKV neuroinvasive disease in our study showed strong overlap with the mRNA profile described in the literature for other viral neuroinvasive diseases. More studies are warranted to decipher the role of cell inflammation and cell death in viral neuroinvasive disease and whether common mechanisms are active in both neurodegenerative and brain infectious diseases.

Genetic epidemiology of pharmacogenetic variants in South East Asian Malays using whole-genome sequences.

PubMed

Sivadas, A; Salleh, M Z; Teh, L K; Scaria, V

2017-10-01

Expanding the scope of pharmacogenomic research by including multiple global populations is integral to building robust evidence for its clinical translation. Deep whole-genome sequencing of diverse ethnic populations provides a unique opportunity to study rare and common pharmacogenomic markers that often vary in frequency across populations. In this study, we aim to build a diverse map of pharmacogenetic variants in South East Asian (SEA) Malay population using deep whole-genome sequences of 100 healthy SEA Malay individuals. We investigated the allelic diversity of potentially deleterious pharmacogenomic variants in SEA Malay population. Our analysis revealed 227 common and 466 rare potentially functional single nucleotide variants (SNVs) in 437 pharmacogenomic genes involved in drug metabolism, transport and target genes, including 74 novel variants. This study has created one of the most comprehensive maps of pharmacogenetic markers in any population from whole genomes and will hugely benefit pharmacogenomic investigations and drug dosage recommendations in SEA Malays.

Chromosome 17 and hereditary dementia: linkage studies in three non-Alzheimer families and kindreds with late-onset FAD.

PubMed

Bird, T D; Wijsman, E M; Nochlin, D; Leehey, M; Sumi, S M; Payami, H; Poorkaj, P; Nemens, E; Rafkind, M; Schellenberg, G D

1997-04-01

Several previous families with differing clinical and pathologic characteristics have demonstrated linkage to the 17q21-22 region. We have performed a linkage analysis with chromosome 17 markers on three families showing autosomal dominant inheritance of non-Alzheimer dementia and 60 kindreds with late-onset familial Alzheimer's disease (FAD). Family A shows unequivocal evidence of linkage with a maximum lod score of 5.0 for marker D17S934 (theta = 0.001). This family has an unusual syndrome of a schizophrenia-like psychosis beginning in the fifth or sixth decade followed by severe dementia with an average disease duration of 13.8 years. Neuropathology from five autopsies in this family has shown marked neurofibrillary tangle formation (NFT), degeneration of the amygdala, and no amyloid plaques. This confirms the presence of a gene associated with dementia on 17q and extends the related phenotype to include schizophrenia-like symptoms and classic NFT pathology. A second family with early aphasia progressing to dementia and cortical-basal ganglion-like degeneration also has suggestive evidence for linkage to 17q. A third family with very early-onset dementia (mean, 31 years) and nonspecific pathology can be excluded from the 17q region and emphasizes additional genetic heterogeneity in non-Alzheimer hereditary dementia. Finally, we also present evidence against linkage to D17S579 in the set of 60 families with late-onset FAD, providing further evidence that the chromosome 17 gene is unlikely to be involved in the pathogenesis of typical AD.

Mapping of a disease susceptibility locus in chromosome 6p in Japanese patients with ulcerative colitis.

PubMed

Nomura, E; Kinouchi, Y; Negoro, K; Kojima, Y; Oomori, S; Sugimura, M; Hiroki, M; Takagi, S; Aihara, H; Takahashi, S; Hiwatashi, N; Shimosegawa, T

2004-09-01

Ulcerative colitis (UC) is a multifactorial disorder with both genetic and environmental factors. HLA-B*52 and DRB1*1502 are reported to be strongly associated with UC in Japan. However, the actual susceptible gene has not been identified yet. In this study, to map precisely the susceptible locus for UC, we performed association mapping in the chromosome 6p using 24 microsatellite markers distributed over 16 Mb. A total of 183 patients with UC and 186 healthy controls (HC) were included in this study. In all, 15 markers around the human leukocyte antigen (HLA) region showed statistical significance in the genotypic differentiation test concerned with the allelic distribution between the UC and HC. Especially, the markers between the centromeric region of HLA class I and the telomeric region of class III showed remarkably low P-values and the allele239 of C2-4-4 in class I marker showed the strongest association (Pc=2.9 x 10(-9): OR=3.74, 95% CI=2.50-5.60). Furthermore, we found strong linkage disequilibrium (LD) between the allele239 of C2-4-4 and HLA-B*52 in haplotype analysis. These results provide evidence that, in Japanese, important determinants of disease susceptibility to UC may exist in HLA, especially between the centromeric region of class I and the telomeric region of class III, under the strong LD with HLA-B*52.

The not face: A grammaticalization of facial expressions of emotion.

PubMed

Benitez-Quiroz, C Fabian; Wilbur, Ronnie B; Martinez, Aleix M

2016-05-01

Facial expressions of emotion are thought to have evolved from the development of facial muscles used in sensory regulation and later adapted to express moral judgment. Negative moral judgment includes the expressions of anger, disgust and contempt. Here, we study the hypothesis that these facial expressions of negative moral judgment have further evolved into a facial expression of negation regularly used as a grammatical marker in human language. Specifically, we show that people from different cultures expressing negation use the same facial muscles as those employed to express negative moral judgment. We then show that this nonverbal signal is used as a co-articulator in speech and that, in American Sign Language, it has been grammaticalized as a non-manual marker. Furthermore, this facial expression of negation exhibits the theta oscillation (3-8 Hz) universally seen in syllable and mouthing production in speech and signing. These results provide evidence for the hypothesis that some components of human language have evolved from facial expressions of emotion, and suggest an evolutionary route for the emergence of grammatical markers. Copyright © 2016 Elsevier B.V. All rights reserved.

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

The Not Face: A grammaticalization of facial expressions of emotion

PubMed Central

Benitez-Quiroz, C. Fabian; Wilbur, Ronnie B.; Martinez, Aleix M.

2016-01-01

Facial expressions of emotion are thought to have evolved from the development of facial muscles used in sensory regulation and later adapted to express moral judgment. Negative moral judgment includes the expressions of anger, disgust and contempt. Here, we study the hypothesis that these facial expressions of negative moral judgment have further evolved into a facial expression of negation regularly used as a grammatical marker in human language. Specifically, we show that people from different cultures expressing negation use the same facial muscles as those employed to express negative moral judgment. We then show that this nonverbal signal is used as a co-articulator in speech and that, in American Sign Language, it has been grammaticalized as a non-manual marker. Furthermore, this facial expression of negation exhibits the theta oscillation (3–8 Hz) universally seen in syllable and mouthing production in speech and signing. These results provide evidence for the hypothesis that some components of human language have evolved from facial expressions of emotion, and suggest an evolutionary route for the emergence of grammatical markers. PMID:26872248

Genetic approaches refine ex situ lowland tapir (Tapirus terrestris) conservation.

PubMed

Gonçalves da Silva, Anders; Lalonde, Danielle R; Quse, Viviana; Shoemaker, Alan; Russello, Michael A

2010-01-01

Ex situ conservation management remains an important tool in the face of continued habitat loss and global environmental change. Here, we use microsatellite marker variation to evaluate conventional assumptions of pedigree-based ex situ population management and directly inform a captive lowland tapir breeding program within a range country. We found relatively high levels of genetic variation (N(total) = 41; mean H(E) = 0.67 across 10 variable loci) and little evidence for relatedness among founder individuals (N(founders) = 10; mean relatedness = -0.05). Seven of 29 putative parent-offspring relationships were excluded by parentage analysis based on allele sharing, and we identified 2 individuals of high genetic value to the population (mk

Targeting CD133 antigen in cancer.

PubMed

Ferrandina, Gabriella; Petrillo, Marco; Bonanno, Giuseppina; Scambia, Giovanni

2009-07-01

Much attention has been focused on CD133 as a marker of cancer cells with stem-cell-like ability. In the cancer stem cells (CSCs) model, only a small proportion of tumour cells are able to self-renew extensively, while the bulk of cells proceed to differentiate into committed heterogeneous clones. On the basis of the involvement of CSCs in tumourigenesis and treatment resistance, it is conceivable that only eradication of CSCs can lead to a cancer cure. To highlight the most recent evidence about the role of CD133 as a marker of CSCs in human tumours, and the therapeutic perspectives associated with its specific targeting. A literature search through Medline to locate published full articles using the following key words for selection: 'CD133 and cancer targeting', 'CD133 and chemo resistance', and 'CD133 and molecular pathways'. Only studies in English are considered. The role of CD133 as a marker of CSCs has been documented in several human neoplasms; its expression seems to predict unfavourable prognosis. Novel therapeutic strategies aimed at targeting molecular pathways critical for CD133+ CSCs survival are being examined.

Boundary-to-Marker Evidence-Controlled Segmentation and MDL-Based Contour Inference for Overlapping Nuclei.

PubMed

Song, Jie; Xiao, Liang; Lian, Zhichao

2017-03-01

This paper presents a novel method for automated morphology delineation and analysis of cell nuclei in histopathology images. Combining the initial segmentation information and concavity measurement, the proposed method first segments clusters of nuclei into individual pieces, avoiding segmentation errors introduced by the scale-constrained Laplacian-of-Gaussian filtering. After that a nuclear boundary-to-marker evidence computing is introduced to delineate individual objects after the refined segmentation process. The obtained evidence set is then modeled by the periodic B-splines with the minimum description length principle, which achieves a practical compromise between the complexity of the nuclear structure and its coverage of the fluorescence signal to avoid the underfitting and overfitting results. The algorithm is computationally efficient and has been tested on the synthetic database as well as 45 real histopathology images. By comparing the proposed method with several state-of-the-art methods, experimental results show the superior recognition performance of our method and indicate the potential applications of analyzing the intrinsic features of nuclei morphology.

Preclinical evaluation of novel urinary biomarkers of cadmium nephrotoxicity

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

Prozialeck, Walter C.; Edwards, Joshua R.; Vaidya, Vishal S.

2009-08-01

As a result of the widespread use of Cd in industry and its extensive dissemination in the environment, there has been considerable interest in the identification of early biomarkers of Cd-induced kidney injury. Kim-1 is a transmembrane glycoprotein that is not detectable in normal kidney, but is up-regulated and shed into the urine following ischemic or nephrotoxic injury. Recent studies utilizing a sub-chronic model of Cd exposure in the rat have shown that Kim-1 is an early urinary marker of Cd-induced kidney injury. Kim-1 was detected in the urine 4-5 weeks before the onset of proteinuria and 1-3 weeks beforemore » the appearance of urinary metallothionein and Clara cell protein 16, which are standard markers of Cd nephrotoxicity. In the present study, we have compared the time course for the appearance of Kim-1 in the urine with the time course for the appearance of alpha glutathione-S-transferase ({alpha}-GST), N-acetyl-{beta}-D-glucose amidase (NAG) and Cd, each of which have been used or proposed as urinary markers of Cd nephrotoxicity. Adult male Sprague-Dawley rats were given daily subcutaneous injections of 0.6 mg (5.36 {mu}moles)/kg Cd, 5 days per week for up to 12 weeks. One day each week, 24 h urine samples were collected and analyzed for protein, creatinine and the various markers. The results showed that significant levels of Kim-1 appeared in the urine as early as 6 weeks into the treatment protocol and then continued to rise for the remainder of the 12 week treatment period. By contrast, significant levels of {alpha}-GST and NAG did not appear in the urine until 8 and 12 weeks, respectively, while proteinuria was not evident until 10 weeks. The urinary excretion of Cd was below the level of detection until week 4 and then showed a slow, linear increase over the next 6 weeks before increasing markedly between weeks 10 and 12. These results provide additional evidence that Kim-1 is a sensitive biomarker of the early stages of Cd-induced proximal tubule injury.« less

Complete remission of a case of hepatocellular carcinoma with tumor invasion in inferior vena cava and with pulmonary metastasis successfully treated with repeated arterial infusion chemotherapy.

PubMed

Kogure, Takayuki; Iwasaki, Takao; Ueno, Yoshiyuki; Kanno, Noriatsu; Fukushima, Koji; Yamagiwa, Yoko; Nagasaki, Futoshi; Kakazu, Eiji; Matsuda, Yasunori; Kido, Osamu; Nakagome, Yu; Ninomiya, Masashi; Shimosegawa, Tooru

2007-01-01

We report the case of a patient having hepatocellular carcinoma with tumor invasion to the inferior vena cava and with multiple pulmonary metastases who was treated with repeated one-shot administration of epirubicin, cisplatin, and mitomycin C by hepatic artery and bronchial artery, which led to complete remission. A 72-year-old woman was diagnosed with infiltrative hepatocellular carcinoma with Vv3, multiple intrahepatic metastases, and multiple pulmonary metastases associated with compensated liver cirrhosis. One-shot infusion of epirubicin, cisplatin, and mitomycin C was performed through proper hepatic artery and bronchial artery for twice at eight weeks of intervals. Pulmonary metastases disappeared and intrahepatic lesions indicated marked shrinkage leaving a scar-like lesion with decreases in tumor markers. After six months and 20 months, tumor markers indicated increasing tendency but no evident recurrence was found by computed tomography or hepatic arteriography. One-shot infusion of the same regimens through proper hepatic artery was performed and tumor markers decreased to normal levels. After 14 months of the last therapy, no evidence of recurrence has been found on image analysis or in tumor markers. This arterial infusion therapy is well tolerated for the patients with compensated liver cirrhosis and might be promising for the effective treatment of advanced hepatocellular carcinoma with pulmonary metastases.

Relationships between Causes of Fever of Unknown Origin and Inflammatory Markers: A Multicenter Collaborative Retrospective Study.

PubMed

Naito, Toshio; Torikai, Keito; Mizooka, Masafumi; Mitsumoto, Fujiko; Kanazawa, Kenji; Ohno, Shiro; Morita, Hiroyuki; Ukimura, Akira; Mishima, Nobuhiko; Otsuka, Fumio; Ohyama, Yoshio; Nara, Noriko; Murakami, Kazunari; Mashiba, Kouichi; Akazawa, Kenichiro; Yamamoto, Koji; Tanei, Mika; Yamanouchi, Masashi; Senda, Shoichi; Tazuma, Susumu; Hayashi, Jun

2015-01-01

Although inflammatory markers, such as the white blood cell (WBC) count, erythrocyte sedimentation rate (ESR) and levels of C-reactive protein (CRP) and procalcitonin, are widely used to differentiate causes of fever of unknown origin (FUO), little is known about the usefulness of this approach. We evaluated relationships between the causes of classical FUO and the levels of inflammatory markers. A nationwide retrospective study including 17 hospitals affiliated with the Japanese Society of Hospital General Medicine was conducted. This study included 121 patients ≥18 years old diagnosed with "classical FUO" (axillary temperature ≥38.0°C at least twice over a ≥3-week period without elucidation of the cause on three outpatient visits or during three days of hospitalization) between January and December 2011. The causative disease was infectious diseases in 28 patients (23.1%), non-infectious inflammatory disease (NIID) in 37 patients (30.6%), malignancy in 13 patients (10.7%), other in 15 patients (12.4%) and unknown in 28 patients (23.1%). The rate of malignancy was significantly higher for a WBC count of <4,000/μL than for a WBC count of 4,000-8,000/μL (p=0.015). Among the patients with a higher WBC count, the rate of FUO due to NIID tended to be higher and the number of unknown cases tended to be lower. All FUO patients with malignancy showed an ESR of >40 mm/h. A normal ESR appeared to constitute powerful evidence for excluding a diagnosis of malignancy. In contrast, the concentrations of both serum CRP and procalcitonin appeared to be unrelated to the causative disease. The present study identified inflammatory markers that should be considered in the differential diagnosis of classical FUO, providing useful information for future diagnosis.

A Seroprevalence Study of Hepatitis B and C Virus Infections in a Hospitalized Population in Romania, an Opportunity for a Better National Prevention and Control Strategy.

PubMed

Popovici, Odette; Molnar, Geza B; Popovici, Florin; Janţă, Denisa; Pistol, Adriana; Azoicăi, Doina

2016-03-01

The most recent prevalence data for hepatitis B virus (HBV) infection in Romania came from an ESEN 2 study (2002), and from a Romanian population-based study performed in 2008. Most of the previous studies were regional and performed in specific groups (blood donors, pregnant women, institutionalized people, etc) and had limited representativeness at the national level, both for HBV and hepatitis C virus (HCV) infection. The scarcity of prevalence data for HBV and HCV infection coming from the routine surveillance was also considered. The aim of our study was to obtain overall and age group specific estimates of the prevalence of HBV and HCV infections markers in Romania, in order to recommend evidence-based public health interventions. The main outcome was the proportion of persons with HBV, HCV and HBV+HCV infection markers, overall and by age group and gender. Our seroprevalence study ensured national representativeness for the targeted hospitalized population. A prospective collection of serum samples in hospital laboratories was completed between September and November 2013, using a systematic sampling. The study respected the confidentiality of personal data. We calculated the sample size using EpiInfo7 and used Z test - Two-tailed probability for statistical significance. The overall prevalence data estimated in our study were HBc Ab 28%, HBs Ag 4.2%, HBs Ab regardless of titer 64.1%, HBs Ab in titer of at least 10 mUI/ml and negative HBc Ab 17.5%; HCV Ab 5.6%; HBc Ab and HCV Ab 2.8%, as markers of double infection. The overall prevalence data estimated in our study for HBs Ag (4.2%) and HCV Ab (5.6%) correspond to a medium endemicity based on the WHO criteria. The estimated prevalence of HBV and HCV infection markers in the study population should represent an opportunity for a better national prevention and control strategy.

Evidence of cryptic introgression in tomato (Solanum lycopersicum L.) based on wild tomato species alleles

PubMed Central

2012-01-01

Background Many highly beneficial traits (e.g. disease or abiotic stress resistance) have been transferred into crops through crosses with their wild relatives. The 13 recognized species of tomato (Solanum section Lycopersicon) are closely related to each other and wild species genes have been extensively used for improvement of the crop, Solanum lycopersicum L. In addition, the lack of geographical barriers has permitted natural hybridization between S. lycopersicum and its closest wild relative Solanum pimpinellifolium in Ecuador, Peru and northern Chile. In order to better understand patterns of S. lycopersicum diversity, we sequenced 47 markers ranging in length from 130 to 1200 bp (total of 24 kb) in genotypes of S. lycopersicum and wild tomato species S. pimpinellifolium, Solanum arcanum, Solanum peruvianum, Solanum pennellii and Solanum habrochaites. Between six and twelve genotypes were comparatively analyzed per marker. Several of the markers had previously been hypothesized as carrying wild species alleles within S. lycopersicum, i.e., cryptic introgressions. Results Each marker was mapped with high confidence (e<1 x 10-30) to a single genomic location using BLASTN against tomato whole genome shotgun chromosomes (SL2.40) database. Neighbor-joining trees showed high mean bootstrap support (86.8 ± 2.34%) for distinguishing red-fruited from green-fruited taxa for 38 of the markers. Hybridization and parsimony splits networks, genomic map positions of markers relative to documented introgressions, and historical origins of accessions were used to interpret evolutionary patterns at nine markers with putatively introgressed alleles. Conclusion Of the 47 genetic markers surveyed in this study, four were involved in linkage drag on chromosome 9 during introgression breeding, while alleles at five markers apparently originated from natural hybridization with S. pimpinellifolium and were associated with primitive genotypes of S. lycopersicum. The positive identification of introgressed genes within crop species such as S. lycopersicum will help inform conservation and utilization of crop germplasm diversity, for example, facilitating the purging of undesirable linkage drag or the exploitation of novel, favorable alleles. PMID:22871151

Genome‐wide linkage analysis of pulmonary function in families of children with asthma in Costa Rica

PubMed Central

Hersh, Craig P; Soto‐Quirós, Manuel E; Avila, Lydiana; Lake, Stephen L; Liang, Catherine; Fournier, Eduardo; Spesny, Mitzi; Sylvia, Jody S; Lazarus, Ross; Hudson, Thomas; Verner, Andrei; Klanderman, Barbara J; Freimer, Nelson B; Silverman, Edwin K; Celedón, Juan C

2007-01-01

Background Although asthma is highly prevalent among certain Hispanic subgroups, genetic determinants of asthma and asthma‐related traits have not been conclusively identified in Hispanic populations. A study was undertaken to identify genomic regions containing susceptibility loci for pulmonary function and bronchodilator responsiveness (BDR) in Costa Ricans. Methods Eight extended pedigrees were ascertained through schoolchildren with asthma in the Central Valley of Costa Rica. Short tandem repeat (STR) markers were genotyped throughout the genome at an average spacing of 8.2 cM. Multipoint variance component linkage analyses of forced expiratory volume in 1 second (FEV1) and FEV1/ forced vital capacity (FVC; both pre‐bronchodilator and post‐bronchodilator) and BDR were performed in these eight families (pre‐bronchodilator spirometry, n = 640; post‐bronchodilator spirometry and BDR, n = 624). Nine additional STR markers were genotyped on chromosome 7. Secondary analyses were repeated after stratification by cigarette smoking. Results Among all subjects, the highest logarithm of the odds of linkage (LOD) score for FEV1 (post‐bronchodilator) was found on chromosome 7q34–35 (LOD = 2.45, including the additional markers). The highest LOD scores for FEV1/FVC (pre‐bronchodilator) and BDR were found on chromosomes 2q (LOD = 1.53) and 9p (LOD = 1.53), respectively. Among former and current smokers there was near‐significant evidence of linkage to FEV1/FVC (post‐bronchodilator) on chromosome 5p (LOD = 3.27) and suggestive evidence of linkage to FEV1 on chromosomes 3q (pre‐bronchodilator, LOD = 2.74) and 4q (post‐bronchodilator, LOD = 2.66). Conclusions In eight families of children with asthma in Costa Rica, there is suggestive evidence of linkage to FEV1 on chromosome 7q34–35. In these families, FEV1/FVC may be influenced by an interaction between cigarette smoking and a locus (loci) on chromosome 5p. PMID:17099076

Molecular diagnosis of populational variants of Anthonomus grandis (Coleoptera: Curculionidae) in North America.

PubMed

Barr, Norman; Ruiz-Arce, Raul; Obregón, Oscar; De Leon, Rosita; Foster, Nelson; Reuter, Chris; Boratynski, Theodore; Vacek, Don

2013-02-01

The utility of the cytochrome oxidase I (COI) DNA sequence used for DNA barcoding and a Sequence Characterized Amplified Region for diagnosing boll weevil, Anthonomus grandis Boheman, variants was evaluated. Maximum likelihood analysis of COI DNA sequences from 154 weevils collected from the United States and Mexico supports previous evidence for limited gene flow between weevil populations on wild cotton and commercial cotton in northern Mexico and southern United States. The wild cotton populations represent a variant of the species called the thurberia weevil, which is not regarded as a significant pest. The 31 boll weevil COI haplotypes observed in the study form two distinct haplogroups (A and B) that are supported by five fixed nucleotide differences and a phylogenetic analysis. Although wild and commercial cotton populations are closely associated with specific haplogroups, there is not a fixed difference between the thurberia weevil variant and other populations. The Sequence Characterized Amplified Region marker generated a larger number of inconclusive results than the COI gene but also supported evidence of shared genotypes between wild and commercial cotton weevil populations. These methods provide additional markers that can assist in the identification of pest weevil populations but not definitively diagnose samples.

Bone formation is not impaired by hibernation (disuse) in black bears Ursus americanus

USGS Publications Warehouse

Donahue, S.W.; Vaughan, M.R.; Demers, L.M.; Donahue, H.J.

2003-01-01

Disuse by bed rest, limb immobilization or space flight causes rapid bone loss by arresting bone formation and accelerating bone resorption. This net bone loss increases the risk of fracture upon remobilization. Bone loss also occurs in hibernating ground squirrels, golden hamsters, and little brown bats by arresting bone formation and accelerating bone resorption. There is some histological evidence to suggest that black bears Ursus americanus do not lose bone mass during hibernation (i.e. disuse). There is also evidence suggesting that muscle mass and strength are preserved in black bears during hibernation. The question of whether bears can prevent bone loss during hibernation has not been conclusively answered. The goal of the current study was to further assess bone metabolism in hibernating black bears. Using the same serum markers of bone remodeling used to evaluate human patients with osteoporosis, we assayed serum from five black bears, collected every 10 days over a 196-day period, for bone resorption and formation markers. Here we show that bone resorption remains elevated over the entire hibernation period compared to the pre-hibernation period, but osteoblastic bone formation is not impaired by hibernation and is rapidly accelerated during remobilization following hibernation.

Fine structure of the 21S ribosomal RNA region on yeast mitochondrial DNA. III. Physical location of mitochondrial genetic markers and the molecular nature of omega.

PubMed

Heyting, C; Menke, H H

1979-01-11

1. We have determined the physical location of mitochondrial genetic markers in the 21S region of yeast mtDNA by genetic analysis of petite mutants whose mtDNA has been physically mapped on the wild-type mtDNA. 2. The order of loci, determined in this study, is in agreement with the order deduced from recombination analysis and coretention analysis except for the position of omega+: we conclude that omega+ is located between C321 (RIB-1) and E514 (RIB-3). 3. The marker E514 (RIB-3) has been localized on a DNA segment of 3800 bp, and the markers E354, E553 and cs23 (RIB-2) on a DNA segment of 1100 base pairs; both these segments overlap the 21S rRNA cistron. The marker C321 (RIB-1) has been localized within a segment of 240 bp which also overlaps the 21S rRNA cistron, and we infer on the basis of indirect evidence that this marker lies within this cistron. 4. In all our rho+ as well as rho- strains there is a one-to-one correlation between the omega+ phenotype, the ability to transmit the omega+ allele and the presence of a mtDNA segment of about 1000 bp long, located between sequences specifying RIB-3 and sequences corresponding to the loci RIB-1 and RIB-2. This segment may be inserted at this same position into omega- mtDNA by recombination. 5. The role which the different allelic forms of omega may play in the polarity of recombination is discussed.

The development of 10 novel polymorphic microsatellite markers through next generation sequencing and a preliminary population genetic analysis for the endangered Glenelg spiny crayfish, Euastacus bispinosus.

PubMed

Miller, Adam D; Van Rooyen, Anthony; Sweeney, Oisín F; Whiterod, Nick S; Weeks, Andrew R

2013-07-01

The Glenelg spiny crayfish, Euastacus bispinosus, is an iconic freshwater invertebrate of south eastern Australia and listed as 'endangered' under the Environment Protection and Biodiversity Conservation Act 1999, and 'vulnerable' under the International Union for Conservation of Nature's Red List. The species has suffered major population declines as a result of over-fishing, low environmental flows, the introduction of invasive fish species and habitat degradation. In order to develop an effective conservation strategy, patterns of gene flow, genetic structure and genetic diversity across the species distribution need to be clearly understood. In this study we develop a suite of polymorphic microsatellite markers by next generation sequencing. A total of 15 polymorphic loci were identified and 10 characterized using 22 individuals from the lower Glenelg River. We observed low to moderate genetic variation across most loci (mean number of alleles per locus = 2.80; mean expected heterozygosity = 0.36) with no evidence of individual loci deviating significantly from Hardy-Weinberg equilibrium. Marker independence was confirmed with tests for linkage disequilibrium, and analyses indicated no evidence of null alleles across loci. Individuals from two additional sites (Crawford River, Victoria; Ewens Ponds Conservation Park, South Australia) were genotyped at all 10 loci and a preliminary investigation of genetic diversity and population structure was undertaken. Analyses indicate high levels of genetic differentiation among sample locations (F ST = 0.49), while the Ewens Ponds population is genetically homogeneous, indicating a likely small founder group and ongoing inbreeding. Management actions will be needed to restore genetic diversity in this and possibly other at risk populations. These markers will provide a valuable resource for future population genetic assessments so that an effective framework can be developed for implementing conservation strategies for E. bispinosus.

Semi-quantitative evaluation of fecal contamination potential by human and ruminant sources using multiple lines of evidence.

PubMed

Stoeckel, Donald M; Stelzer, Erin A; Stogner, Robert W; Mau, David P

2011-05-01

Protocols for microbial source tracking of fecal contamination generally are able to identify when a source of contamination is present, but thus far have been unable to evaluate what portion of fecal-indicator bacteria (FIB) came from various sources. A mathematical approach to estimate relative amounts of FIB, such as Escherichia coli, from various sources based on the concentration and distribution of microbial source tracking markers in feces was developed. The approach was tested using dilute fecal suspensions, then applied as part of an analytical suite to a contaminated headwater stream in the Rocky Mountains (Upper Fountain Creek, Colorado). In one single-source fecal suspension, a source that was not present could not be excluded because of incomplete marker specificity; however, human and ruminant sources were detected whenever they were present. In the mixed-feces suspension (pet and human), the minority contributor (human) was detected at a concentration low enough to preclude human contamination as the dominant source of E. coli to the sample. Without the semi-quantitative approach described, simple detects of human-associated marker in stream samples would have provided inaccurate evidence that human contamination was a major source of E. coli to the stream. In samples from Upper Fountain Creek the pattern of E. coli, general and host-associated microbial source tracking markers, nutrients, and wastewater-associated chemical detections--augmented with local observations and land-use patterns--indicated that, contrary to expectations, birds rather than humans or ruminants were the predominant source of fecal contamination to Upper Fountain Creek. This new approach to E. coli allocation, validated by a controlled study and tested by application in a relatively simple setting, represents a widely applicable step forward in the field of microbial source tracking of fecal contamination. Copyright © 2011 Elsevier Ltd. All rights reserved.

Determination of tobacco smoking influence on volatile organic compounds constituent by indoor tobacco smoking simulation experiment

NASA Astrophysics Data System (ADS)

Xie, Juexin; Wang, Xingming; Sheng, Guoying; Bi, Xinhui; Fu, Jiamo

Tobacco smoking simulation experiment was conducted in a test room under different conditions such as cigarette brands, smoking number, and post-smoke decay in forced ventilation or in closed indoor environments. Thirty-seven chemical species were targeted and monitored, including volatile organic compounds (VOCs) and environmental tobacco smoke (ETS) markers. The results indicate that benzene, d-limonene, styrene, m-ethyltoluene and 1,2,4/1,3,5-trimethylbenzene are correlated well with ETS markers, but toluene, xylene, and ethylbenzene are not evidently correlated with ETS markers because there are some potential indoor sources of these compounds. 2,5-dimethylfuran is considered to be a better ETS marker due to the relative stability in different cigarette brands and a good relationship with other ETS markers. The VOCs concentrations emitted by tobacco smoking were linearly associated with the number of cigarettes consumed, and different behaviors were observed in closed indoor environment, of which ETS markers, d-limonene, styrene, trimethylbenzene, etc. decayed fast, whereas benzene, toluene, xylene, ethylbenzene, etc. decayed slowly and even increased in primary periods of the decay; hence ETS exposure in closed environments is believed to be more dangerous. VOCs concentrations and the relative percentage constituent of ETS markers of different brand cigarettes emissions vary largely, but the relative percentage constituent of ETS markers for the same brand cigarette emissions is similar.

The US Food and Drug Administration's expedited approval programs: Evidentiary standards, regulatory trade-offs, and potential improvements.

PubMed

Wallach, Joshua D; Ross, Joseph S; Naci, Huseyin

2018-06-01

The US Food and Drug Administration has several regulatory programs and pathways to expedite the development and approval of therapeutic agents aimed at treating serious or life-debilitating conditions. A common feature of these programs is the regulatory flexibility, which allows for a customized approval approach that enables market authorization on the basis of less rigorous evidence, in exchange for requiring postmarket evidence generation. An increasing share of therapeutic agents approved by the Food and Drug Administration in recent years are associated with expedited programs. In this article, we provide an overview of the evidentiary standards required by the Food and Drug Administration's expedited development and review programs, summarize the findings of the recent academic literature demonstrating some of the limitations of these programs, and outline potential opportunities to address these limitations. Recent evidence suggests that therapeutic agents in the Food and Drug Administration's expedited programs are approved on the basis of fewer and smaller studies that may lack comparator groups and random allocation, and rather than focusing on clinical outcomes for study endpoints, rely instead on surrogate markers of disease. Once on the market, agents receiving expedited approvals are often quickly incorporated into clinical practice, and evidence generated in the postmarket period may not necessarily address the evidentiary limitations at the time of market entry. Furthermore, not all pathways require additional postmarket studies. Evidence suggests that drugs in expedited approval programs are associated with a greater likelihood that the Food and Drug Administration will take a safety action following market entry. There are several opportunities to improve the timeliness, information value, and validity of the pre- and postmarket studies of therapeutic agents receiving expedited approvals. When use of nonrandomized and uncontrolled studies cannot be avoided prior to market entry, randomized trials should be mandatory in the postmarket period, unless there are strong justifications for not carrying out such studies. In the premarket period, validity of the surrogate markers can be improved by more rigorously evaluating their correlation with patient-relevant clinical outcomes. Opportunities to reduce the duration, complexity, and cost of postmarket randomized trials should not compromise their validity and instead incorporate pragmatic "real-world" design elements. Despite recent enthusiasm for widely using real-world evidence, adaptive designs, and pragmatic trials in the regulatory setting, caution is warranted until large-scale empirical evaluations demonstrate their validity compared to more traditional trial designs.

Molecular and histological study on the effects of non-thermal irreversible electroporation on the liver.

PubMed

Zhang, Yanfang; Lyu, Chenang; Liu, Yu; Lv, Yanpeng; Chang, Tammy T; Rubinsky, Boris

2018-06-07

Non-thermal irreversible electroporation (NTIRE) is a biophysical phenomenon in which certain electric fields delivered across the cell membrane in tissue, cause cell death, without affecting the extracellular matrix. "Minimally invasive regenerative surgery" is a new medical modality for treatment of end-stage organ or tissue failure in which exogenous cells are implanted in a decellularized niche in tissue, formed by the delivery of NTIRE electric fields across a targeted volume of tissue. We anticipate that the success of the procedure will depend on the time of implantation relative to the application of NTIRE. This study was performed to elucidate the histological and molecular events that occur within 24 h after NTIRE, in the context of optimal criteria for the time of implantation. To this end, we examined the histology of NTIRE treated rat liver with H&E, Masson trichrome and TUNEL staining. Western blot was used to examine pro and cleaved caspase-3 (marker for apoptosis), pro and cleaved caspase-1 and gasdermin D (markers for pyroptosis), and RIP3 and MLKL (markers for necroptosis). The key findings are that, complete hepatocytes disintegration within an intact extracellular matrix is seen at 6 h and, new hepatocytes are seen in the treated region at 24 h, after NTIRE. There is no evidence of apoptotic cell death from NTIRE, contrary to commonly made claims in the NTIRE literature. However, molecular pathways of pyroptosis and necroptosis, programed necrosis associated with inflammation, are activated at 6 h after NTIRE and are not evident at 24 h after NTIRE. These are fundamental new findings of basic value to the field of NTIRE in all its applications. Taken together the results suggest the hypothesis that an optimal time for implantation is about 24 h after NTIRE. Future studies in which exogenous cells are implanted at different times after NTIRE are required to examine this hypothesis. Copyright © 2018 Elsevier Inc. All rights reserved.

Chromosome evolution in Cophomantini (Amphibia, Anura, Hylinae).

PubMed

Ferro, Juan M; Cardozo, Dario E; Suárez, Pablo; Boeris, Juan M; Blasco-Zúñiga, Ailin; Barbero, Gastón; Gomes, Anderson; Gazoni, Thiago; Costa, William; Nagamachi, Cleusa Y; Rivera, Miryan; Parise-Maltempi, Patricia P; Wiley, John E; Pieczarka, Julio C; Haddad, Celio F B; Faivovich, Julián; Baldo, Diego

2018-01-01

The hylid tribe Cophomantini is a diverse clade of Neotropical treefrogs composed of the genera Aplastodiscus, Boana, Bokermannohyla, Hyloscirtus, and Myersiohyla. The phylogenetic relationships of Cophomantini have been comprehensively reviewed in the literature, providing a suitable framework for the study of chromosome evolution. Employing different banding techniques, we studied the chromosomes of 25 species of Boana and 3 of Hyloscirtus; thus providing, for the first time, data for Hyloscirtus and for 15 species of Boana. Most species showed karyotypes with 2n = 2x = 24 chromosomes; some species of the B. albopunctata group have 2n = 2x = 22, and H. alytolylax has 2n = 2x = 20. Karyotypes are all bi-armed in most species presented, with the exception of H. larinopygion (FN = 46) and H. alytolylax (FN = 38), with karyotypes that have a single pair of small telocentric chromosomes. In most species of Boana, NORs are observed in a single pair of chromosomes, mostly in the small chromosomes, although in some species of the B. albopunctata, B. pulchella, and B. semilineata groups, this marker occurs on the larger pairs 8, 1, and 7, respectively. In Hyloscirtus, NOR position differs in the three studied species: H. alytolylax (4p), H. palmeri (4q), and H. larinopygion (1p). Heterochromatin is a variable marker that could provide valuable evidence, but it would be necesserary to understand the molecular composition of the C-bands that are observed in different species in order to test its putative homology. In H. alytolylax, a centromeric DAPI+ band was observed on one homologue of chromosome pair 2. The band was present in males but absent in females, providing evidence for an XX/XY sex determining system in this species. We review and discuss the importance of the different chromosome markers (NOR position, C-bands, and DAPI/CMA3 patterns) for their impact on the taxonomy and karyotype evolution in Cophomantini.

Chromosome evolution in Cophomantini (Amphibia, Anura, Hylinae)

PubMed Central

Suárez, Pablo; Boeris, Juan M.; Blasco-Zúñiga, Ailin; Barbero, Gastón; Gomes, Anderson; Gazoni, Thiago; Costa, William; Nagamachi, Cleusa Y.; Rivera, Miryan; Parise-Maltempi, Patricia P.; Wiley, John E.; Pieczarka, Julio C.; Haddad, Celio F. B.; Faivovich, Julián; Baldo, Diego

2018-01-01

The hylid tribe Cophomantini is a diverse clade of Neotropical treefrogs composed of the genera Aplastodiscus, Boana, Bokermannohyla, Hyloscirtus, and Myersiohyla. The phylogenetic relationships of Cophomantini have been comprehensively reviewed in the literature, providing a suitable framework for the study of chromosome evolution. Employing different banding techniques, we studied the chromosomes of 25 species of Boana and 3 of Hyloscirtus; thus providing, for the first time, data for Hyloscirtus and for 15 species of Boana. Most species showed karyotypes with 2n = 2x = 24 chromosomes; some species of the B. albopunctata group have 2n = 2x = 22, and H. alytolylax has 2n = 2x = 20. Karyotypes are all bi-armed in most species presented, with the exception of H. larinopygion (FN = 46) and H. alytolylax (FN = 38), with karyotypes that have a single pair of small telocentric chromosomes. In most species of Boana, NORs are observed in a single pair of chromosomes, mostly in the small chromosomes, although in some species of the B. albopunctata, B. pulchella, and B. semilineata groups, this marker occurs on the larger pairs 8, 1, and 7, respectively. In Hyloscirtus, NOR position differs in the three studied species: H. alytolylax (4p), H. palmeri (4q), and H. larinopygion (1p). Heterochromatin is a variable marker that could provide valuable evidence, but it would be necesserary to understand the molecular composition of the C-bands that are observed in different species in order to test its putative homology. In H. alytolylax, a centromeric DAPI+ band was observed on one homologue of chromosome pair 2. The band was present in males but absent in females, providing evidence for an XX/XY sex determining system in this species. We review and discuss the importance of the different chromosome markers (NOR position, C-bands, and DAPI/CMA3 patterns) for their impact on the taxonomy and karyotype evolution in Cophomantini. PMID:29444174

Genome-wide association study for feed efficiency and growth traits in U.S. beef cattle.

PubMed

Seabury, Christopher M; Oldeschulte, David L; Saatchi, Mahdi; Beever, Jonathan E; Decker, Jared E; Halley, Yvette A; Bhattarai, Eric K; Molaei, Maral; Freetly, Harvey C; Hansen, Stephanie L; Yampara-Iquise, Helen; Johnson, Kristen A; Kerley, Monty S; Kim, JaeWoo; Loy, Daniel D; Marques, Elisa; Neibergs, Holly L; Schnabel, Robert D; Shike, Daniel W; Spangler, Matthew L; Weaber, Robert L; Garrick, Dorian J; Taylor, Jeremy F

2017-05-18

Single nucleotide polymorphism (SNP) arrays for domestic cattle have catalyzed the identification of genetic markers associated with complex traits for inclusion in modern breeding and selection programs. Using actual and imputed Illumina 778K genotypes for 3887 U.S. beef cattle from 3 populations (Angus, Hereford, SimAngus), we performed genome-wide association analyses for feed efficiency and growth traits including average daily gain (ADG), dry matter intake (DMI), mid-test metabolic weight (MMWT), and residual feed intake (RFI), with marker-based heritability estimates produced for all traits and populations. Moderate and/or large-effect QTL were detected for all traits in all populations, as jointly defined by the estimated proportion of variance explained (PVE) by marker effects (PVE ≥ 1.0%) and a nominal P-value threshold (P ≤ 5e-05). Lead SNPs with PVE ≥ 2.0% were considered putative evidence of large-effect QTL (n = 52), whereas those with PVE ≥ 1.0% but < 2.0% were considered putative evidence for moderate-effect QTL (n = 35). Identical or proximal lead SNPs associated with ADG, DMI, MMWT, and RFI collectively supported the potential for either pleiotropic QTL, or independent but proximal causal mutations for multiple traits within and between the analyzed populations. Marker-based heritability estimates for all investigated traits ranged from 0.18 to 0.60 using 778K genotypes, or from 0.17 to 0.57 using 50K genotypes (reduced from Illumina 778K HD to Illumina Bovine SNP50). An investigation to determine if QTL detected by 778K analysis could also be detected using 50K genotypes produced variable results, suggesting that 50K analyses were generally insufficient for QTL detection in these populations, and that relevant breeding or selection programs should be based on higher density analyses (imputed or directly ascertained). Fourteen moderate to large-effect QTL regions which ranged from being physically proximal (lead SNPs ≤ 3Mb) to fully overlapping for RFI, DMI, ADG, and MMWT were detected within and between populations, and included evidence for pleiotropy, proximal but independent causal mutations, and multi-breed QTL. Bovine positional candidate genes for these traits were functionally conserved across vertebrate species.

Prognostic markers in localized prostate cancer: from microscopes to molecules.

PubMed

Harding, M A; Theodorescu, D

Management of patients diagnosed with localized prostate cancer is complicated by the diverse natural history of the disease and variable response to treatment. Prognostic criteria currently in use cannot fully predict tumor behavior and thus limit the ability to recommend treatment regimens with the assurance that they are the best course of action for each individual patient. The search for better prognostic markers is now focussed on the molecular mechanisms which underlay tumor behavior, such as altered cell cycle progression, apoptosis, neuroendocrine differentiation, and angiogenesis. As the number of potential molecular markers increases, it is becoming evident that no single marker will provide the prognostic information necessary to make a significant improvement in patient care. In addition, it seems likely that traditional methods of assessing the prognostic value of this multitude of new markers will prove inadequate. In this review, we briefly examine the current state of prognostication in localized prostate cancer and some of the promising new molecular markers. Next, we examine how new technologies may allow the multiplex analysis of vast numbers of markers and how computational methods such as artificial neural networks will provide meaningful interpretation of the data. In the near future, such an integrated approach may provide a comprehensive prognostic tool for localized prostate cancer.

An Expressed Sequence Tag (EST)-enriched genetic map of turbot (Scophthalmus maximus): a useful framework for comparative genomics across model and farmed teleosts

PubMed Central

2012-01-01

Background The turbot (Scophthalmus maximus) is a relevant species in European aquaculture. The small turbot genome provides a source for genomics strategies to use in order to understand the genetic basis of productive traits, particularly those related to sex, growth and pathogen resistance. Genetic maps represent essential genomic screening tools allowing to localize quantitative trait loci (QTL) and to identify candidate genes through comparative mapping. This information is the backbone to develop marker-assisted selection (MAS) programs in aquaculture. Expressed sequenced tag (EST) resources have largely increased in turbot, thus supplying numerous type I markers suitable for extending the previous linkage map, which was mostly based on anonymous loci. The aim of this study was to construct a higher-resolution turbot genetic map using EST-linked markers, which will turn out to be useful for comparative mapping studies. Results A consensus gene-enriched genetic map of the turbot was constructed using 463 SNP and microsatellite markers in nine reference families. This map contains 438 markers, 180 EST-linked, clustered at 24 linkage groups. Linkage and comparative genomics evidences suggested additional linkage group fusions toward the consolidation of turbot map according to karyotype information. The linkage map showed a total length of 1402.7 cM with low average intermarker distance (3.7 cM; ~2 Mb). A global 1.6:1 female-to-male recombination frequency (RF) ratio was observed, although largely variable among linkage groups and chromosome regions. Comparative sequence analysis revealed large macrosyntenic patterns against model teleost genomes, significant hits decreasing from stickleback (54%) to zebrafish (20%). Comparative mapping supported particular chromosome rearrangements within Acanthopterygii and aided to assign unallocated markers to specific turbot linkage groups. Conclusions The new gene-enriched high-resolution turbot map represents a useful genomic tool for QTL identification, positional cloning strategies, and future genome assembling. This map showed large synteny conservation against model teleost genomes. Comparative genomics and data mining from landmarks will provide straightforward access to candidate genes, which will be the basis for genetic breeding programs and evolutionary studies in this species. PMID:22747677

Transcriptomic markers meet the real world: finding diagnostic signatures of corticosteroid treatment in commercial beef samples

PubMed Central

2012-01-01

Background The use of growth-promoters in beef cattle, despite the EU ban, remains a frequent practice. The use of transcriptomic markers has already proposed to identify indirect evidence of anabolic hormone treatment. So far, such approach has been tested in experimentally treated animals. Here, for the first time commercial samples were analyzed. Results Quantitative determination of Dexamethasone (DEX) residues in the urine collected at the slaughterhouse was performed by Liquid Chromatography-Mass Spectrometry (LC-MS). DNA-microarray technology was used to obtain transcriptomic profiles of skeletal muscle in commercial samples and negative controls. LC-MS confirmed the presence of low level of DEX residues in the urine of the commercial samples suspect for histological classification. Principal Component Analysis (PCA) on microarray data identified two clusters of samples. One cluster included negative controls and a subset of commercial samples, while a second cluster included part of the specimens collected at the slaughterhouse together with positives for corticosteroid treatment based on thymus histology and LC-MS. Functional analysis of the differentially expressed genes (3961) between the two groups provided further evidence that animals clustering with positive samples might have been treated with corticosteroids. These suspect samples could be reliably classified with a specific classification tool (Prediction Analysis of Microarray) using just two genes. Conclusions Despite broad variation observed in gene expression profiles, the present study showed that DNA-microarrays can be used to find transcriptomic signatures of putative anabolic treatments and that gene expression markers could represent a useful screening tool. PMID:23110699

Genetic diversity and structure of wild populations of Carica papaya in Northern Mesoamerica inferred by nuclear microsatellites and chloroplast markers.

PubMed

Chávez-Pesqueira, Mariana; Núñez-Farfán, Juan

2016-12-01

Few studies have evaluated the genetic structure and evolutionary history of wild varieties of important crop species. The wild papaya (Carica papaya) is a key element of early successional tropical and sub-tropical forests in Mexico, and constitutes the genetic reservoir for evolutionary potential of the species. In this study we aimed to determine how diverse and structured is the genetic variability of wild populations of C. papaya in Northern Mesoamerica. Moreover, we assessed if genetic structure and evolutionary history coincide with hypothetized (1) pre-Pleistocene events (Isthmus of Tehuantepec sinking), (2) Pleistocene refugia or (3) recent patterns. We used six nuclear and two chloroplast (cp) DNA markers to assess the genetic diversity and phylogeographical structure of 19 wild populations of C. papaya in its natural distribution in Northern Mesoamerica. We found high genetic diversity (H o = 0·681 for nuclear markers, and h = 0·701 for cpDNA markers) and gene flow between populations of C. papaya (migration r up to 420 km). A lack of phylogeographical structure was found with the cpDNA markers (NST < GST), whereas a recent population structure was inferred with the nuclear markers. Evidence indicates that pre-Pleistocene events or refugia did not play an important role in the genetic structuring of wild papaya. Because of its life history characteristics and lack of an ancient phylogeographical structure found with the cpDNA markers, we suggest that C. papaya was dispersed throughout the lowland rain forests of Mexico (along the coastal plains and foothills of Sierras). This scenario supports the hypothesis that tropical forests in Northern Mesoamerica did not experience important climate fluctuations during the Pleistocene, and that the life history of C. papaya could have promoted long-distance dispersal and rapid colonization of lowland rainforests. Moreover, the results obtained with the nuclear markers suggest recent human disturbances. The fragmentation of tropical habitats in Northern Mesoamerica appears to be the main driver of genetic structuring, and the major threat to the dispersion and survival of the species in the wild. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Maternal uniparental disomy for human chromosome 14, due to loss of a chromosome 14 from somatic cells with t(13; 14) trisomy 14

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

Antonarakis, S.E.; Blouin, J.L.; Maher, J.

1993-06-01

Uniparental disomy (UPD) for particular chromosomes is increasingly recognized as a cause of abnormal phenotypes in humans. The authors recently studied a 9-year-old female with a de novo Robertsonian translocation t(13;14), short stature, mild developmental delay, scoliosis, hyperextensible joints, hydrocephalus that resolved spontaneously during the first year of life, and hyperchloesterolemia. To determine the parental origin of chromosomes 13 and 14 in the proband, they have studied the genotypes of DNA polymorphic markers due to (GT)n repeats in the patient and her parents' blood DNA. The genotypes of markers D14S43, D14S45, D14S49, and D14S54 indicated maternal UPD for chromosome 14.more » There was isodisomy for proximal markers and heterodisomy for distal markers, suggesting a recombination event on maternal chromosomes 14. In addition, DNA analysis first revealed -- and subsequent cytogenetic analysis confirmed -- that there was mosaic trisomy 14 in 5% of blood lymphocytes. There was normal (biparental) inheritance for chromosome 13, and there was no evidence of false paternity in genotypes of 11 highly polymorphic markers on human chromosome 21. Two cases of maternal UPD for chromosome 14 have previously been reported, one with a familial rob t(13;14) and the other with a t(14;14). There are several similarities among these patients, and a [open quotes]maternal UPD chromosome 14 syndrome[close quotes] is emerging; however, the contribution of the mosaic trisomy 14 to the phenotype cannot be evaluated. The study of de novo Robertsonian translocations of the type reported here should reveal both the extent of UPD in these events and the contribution of particular chromosomes involved in certain phenotypes. 33 refs., 3 figs., 1 tab.« less

Patterning of mammalian somites by surface ectoderm and notochord: evidence for sclerotome induction by a hedgehog homolog.

PubMed

Fan, C M; Tessier-Lavigne, M

1994-12-30

An early step in the development of vertebrae, ribs, muscle, and dermis is the differentiation of the somitic mesoderm into dermomyotome dorsally and sclerotome ventrally. To analyze this process, we have developed an in vitro assay for somitic mesoderm differentiation. We show that sclerotomal markers can be induced by a diffusible factor secreted by notochord and floor plate and that heterologous cells expressing Sonic hedgehog (shh/vhh-1) mimic this effect. In contrast, expression of dermomyotomal markers can be caused by a contact-dependent signal from surface ectoderm and a diffusible signal from dorsal neural tube. Our results extend previous studies by suggesting that dorsoventral patterning of somites involves the coordinate action of multiple dorsalizing and ventralizing signals and that a diffusible form of Shh/Vhh-1 mediates sclerotome induction.

Social relationships and inflammatory markers: an analysis of Taiwan and the U.S.

PubMed

Glei, Dana A; Goldman, Noreen; Ryff, Carol D; Lin, Yu-Hsuan; Weinstein, Maxine

2012-06-01

We evaluated the association between two aspects of social relationships and six inflammatory markers in Taiwan and the U.S. These two countries share similar levels of current life expectancy, but exhibit important differences in social structure. The data comprised population based samples from Taiwan (aged 53+; n=962) and the U.S. (aged 35-86; n=990) collected between 2003 and 2009. Circulating levels of interleukin-6 (IL-6), C-reactive protein (CRP), fibrinogen, and soluble forms of intercellular adhesion molecule 1, E-selectin, and IL-6 receptor (sIL-6R) were measured in fasting blood samples. A social integration score was based on marital status, contact with family and friends, church attendance, and other social participation. A perceived social support index was based on questions regarding the availability of care and support from family and friends. Linear regression models tested the association between these two measures and each inflammatory marker controlling for sociodemographic characteristics, obesity, medication use, and baseline health status. After adjusting for potential confounders, social integration had a significant but weak inverse association with CRP in Taiwan. Perceived social support was significant in two of 12 models, and the coefficient was positive (i.e., higher support was associated with higher CRP and sIL-6R in the U.S.). We found no evidence that the coefficients for social relationship measures varied by sex or age. Our results yielded limited evidence of a weak association between two dimensions of social relationships and six inflammatory markers in Taiwan and the U.S. Given that the literature suggests a strong link between social relationships and mortality, and that inflammation plays an important role in the leading causes of death, we had expected to find consistent and moderately strong associations between social relationships and inflammatory markers. The small effect sizes and lack of robustness across markers were surprising. Copyright © 2012 Elsevier Ltd. All rights reserved.

Social Relationships and Inflammatory Markers: An Analysis of Taiwan and the U.S.

PubMed Central

Glei, Dana A.; Goldman, Noreen; Ryff, Carol D.; Lin, Yu-Hsuan; Weinstein, Maxine

2012-01-01

We evaluated the association between two aspects of social relationships and six inflammatory markers in Taiwan and the U.S. These two countries share similar levels of current life expectancy, but exhibit important differences in social structure. The data comprised population based samples from Taiwan (aged 53+; n = 962) and the U.S. (aged 35-86; n = 990) collected between 2003 and 2009. Circulating levels of interleukin-6 (IL-6), C-reactive protein (CRP), fibrinogen, and soluble forms of intercellular adhesion molecule 1, E-selectin, and IL-6 receptor (sIL-6R) were measured in fasting blood samples. A social integration score was based on marital status, contact with family and friends, church attendance, and other social participation. A perceived social support index was based on questions regarding the availability of care and support from family and friends. Linear regression models tested the association between these two measures and each inflammatory marker controlling for sociodemographic characteristics, obesity, medication use, and baseline health status. After adjusting for potential confounders, social integration had a significant but weak inverse association with CRP in Taiwan. Perceived social support was significant in two of 12 models, and the coefficient was positive (i.e., higher support was associated with higher CRP and sIL-6R in the U.S.). We found no evidence that the coefficients for social relationship measures varied by sex or age. Our results yielded limited evidence of a weak association between two dimensions of social relationships and six inflammatory markers in Taiwan and the U.S. Given that the literature suggests a strong link between social relationships and mortality, and that inflammation plays an important role in the leading causes of death, we had expected to find consistent and moderately strong associations between social relationships and inflammatory markers. The small effect sizes and lack of robustness across markers were surprising. PMID:22483707

A first linkage map and downy mildew resistance QTL discovery for sweet basil (Ocimum basilicum) facilitated by double digestion restriction site associated DNA sequencing (ddRADseq).

PubMed

Pyne, Robert; Honig, Josh; Vaiciunas, Jennifer; Koroch, Adolfina; Wyenandt, Christian; Bonos, Stacy; Simon, James

2017-01-01

Limited understanding of sweet basil (Ocimum basilicum L.) genetics and genome structure has reduced efficiency of breeding strategies. This is evidenced by the rapid, worldwide dissemination of basil downy mildew (Peronospora belbahrii) in the absence of resistant cultivars. In an effort to improve available genetic resources, expressed sequence tag simple sequence repeat (EST-SSR) and single nucleotide polymorphism (SNP) markers were developed and used to genotype the MRI x SB22 F2 mapping population, which segregates for response to downy mildew. SNP markers were generated from genomic sequences derived from double digestion restriction site associated DNA sequencing (ddRADseq). Disomic segregation was observed in both SNP and EST-SSR markers providing evidence of an O. basilicum allotetraploid genome structure and allowing for subsequent analysis of the mapping population as a diploid intercross. A dense linkage map was constructed using 42 EST-SSR and 1,847 SNP markers spanning 3,030.9 cM. Multiple quantitative trait loci (QTL) model (MQM) analysis identified three QTL that explained 37-55% of phenotypic variance associated with downy mildew response across three environments. A single major QTL, dm11.1 explained 21-28% of phenotypic variance and demonstrated dominant gene action. Two minor QTL dm9.1 and dm14.1 explained 5-16% and 4-18% of phenotypic variance, respectively. Evidence is provided for an additive effect between the two minor QTL and the major QTL dm11.1 increasing downy mildew susceptibility. Results indicate that ddRADseq-facilitated SNP and SSR marker genotyping is an effective approach for mapping the sweet basil genome.

A first linkage map and downy mildew resistance QTL discovery for sweet basil (Ocimum basilicum) facilitated by double digestion restriction site associated DNA sequencing (ddRADseq)

PubMed Central

Honig, Josh; Vaiciunas, Jennifer; Koroch, Adolfina; Wyenandt, Christian; Bonos, Stacy; Simon, James

2017-01-01

Limited understanding of sweet basil (Ocimum basilicum L.) genetics and genome structure has reduced efficiency of breeding strategies. This is evidenced by the rapid, worldwide dissemination of basil downy mildew (Peronospora belbahrii) in the absence of resistant cultivars. In an effort to improve available genetic resources, expressed sequence tag simple sequence repeat (EST-SSR) and single nucleotide polymorphism (SNP) markers were developed and used to genotype the MRI x SB22 F2 mapping population, which segregates for response to downy mildew. SNP markers were generated from genomic sequences derived from double digestion restriction site associated DNA sequencing (ddRADseq). Disomic segregation was observed in both SNP and EST-SSR markers providing evidence of an O. basilicum allotetraploid genome structure and allowing for subsequent analysis of the mapping population as a diploid intercross. A dense linkage map was constructed using 42 EST-SSR and 1,847 SNP markers spanning 3,030.9 cM. Multiple quantitative trait loci (QTL) model (MQM) analysis identified three QTL that explained 37–55% of phenotypic variance associated with downy mildew response across three environments. A single major QTL, dm11.1 explained 21–28% of phenotypic variance and demonstrated dominant gene action. Two minor QTL dm9.1 and dm14.1 explained 5–16% and 4–18% of phenotypic variance, respectively. Evidence is provided for an additive effect between the two minor QTL and the major QTL dm11.1 increasing downy mildew susceptibility. Results indicate that ddRADseq-facilitated SNP and SSR marker genotyping is an effective approach for mapping the sweet basil genome. PMID:28922359

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

Y-chromosomal testing of brown bears (Ursus arctos): Validation of a multiplex PCR-approach for nine STRs suitable for fecal and hair samples.

PubMed

Aarnes, Siv Grethe; Hagen, Snorre B; Andreassen, Rune; Schregel, Julia; Knappskog, Per M; Hailer, Frank; Stenhouse, Gordon; Janke, Axel; Eiken, Hans Geir

2015-11-01

High-resolution Y-chromosomal markers have been applied to humans and other primates to study population genetics, migration, social structures and reproduction. Y-linked markers allow the direct assessment of the genetic structure and gene flow of uniquely male inherited lineages and may also be useful for wildlife conservation and forensics, but have so far been available only for few wild species. Thus, we have developed two multiplex PCR reactions encompassing nine Y-STR markers identified from the brown bear (Ursus arctos) and tested them on hair, fecal and tissue samples. The multiplex PCR approach was optimized and analyzed for species specificity, sensitivity and stutter-peak ratios. The nine Y-STRs also showed specific STR-fragments for male black bears and male polar bears, while none of the nine markers produced any PCR products when using DNA from female bears or males from 12 other mammals. The multiplex PCR approach in two PCR reactions could be amplified with as low as 0.2 ng template input. Precision was high in DNA templates from hairs, fecal scats and tissues, with standard deviations less than 0.14 and median stutter ratios from 0.04 to 0.63. Among the eight di- and one tetra-nucleotide repeat markers, we detected simple repeat structures in seven of the nine markers with 9-25 repeat units. Allelic variation was found for eight of the nine Y-STRs, with 2-9 alleles for each marker and a total of 36 alleles among 453 male brown bears sampled mainly from Northern Europe. We conclude that the multiplex PCR approach with these nine Y-STRs would provide male bear Y-chromosomal specificity and evidence suited for samples from conservation and wildlife forensics. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Study on sequence characterized amplified region (SCAR) markers of Cornus officinalis].

PubMed

Chen, Suiqing; Lu, Xiaolei; Wang, Lili

2011-05-01

To establish sequence characterized amplified region markers of Cornus officinalis and provide a scientific basis for molecular identification of C. officinalis. The random primer was screened through RAPD to obtain specific RAPD marker bands. The RAPD marker bands were separated, extracted, cloned and sequenced. Both ends of the sequence of RAPD marker bands were determined. A pair of specific primers was designed for conventional PCR reaction, and SCAR marker was acquired. Four pairs of primers were designed based on the sequence of RAPD marker bands. The DNA of the seven varieties of C. officinalis was amplified by using YST38 and YST43 primer. The results showed that seven varieties of C. officinalis were able to produce a single PCR product. It was an effective way to identify C. officinalis. The varieties with cylindrical and long-pear shape fruits amplified by YST38 showed a specific band, which could be used as the evidence of variety identification. Seven varieties of C. oficinalis were amplified by using primer YST39. But the size of band of the variety with spindly shape fruit (35,0400 bp) was about 300 bp, which was shorter than those of the variety with the other shape fruits of C. officinalis (650-700 bp). The variety with the spindly shape fruit could be identified through this difference. The primer YST92 could produce a fragment from 600-700 bp in the varieties with cylindrical and long-pear shape fruits, a fragment from 200-300 bp in the varieties with oval and short-cylindrical shape fruits and had no fragment in the varieties with long cylindrical, elliptic and short-pear shape fruits, which could be used to select the different shapes of C. officinalis. SCAR mark is established and can be used as the basis for breeding and distinguishing the verieties of C. officinalis.

Control of Origin of Sesame Oil from Various Countries by Stable Isotope Analysis and DNA Based Markers—A Pilot Study

PubMed Central

Horacek, Micha; Hansel-Hohl, Karin; Burg, Kornel; Soja, Gerhard; Okello-Anyanga, Walter; Fluch, Silvia

2015-01-01

The indication of origin of sesame seeds and sesame oil is one of the important factors influencing its price, as it is produced in many regions worldwide and certain provenances are especially sought after. We joined stable carbon and hydrogen isotope analysis with DNA based molecular marker analysis to study their combined potential for the discrimination of different origins of sesame seeds. For the stable carbon and hydrogen isotope data a positive correlation between both isotope parameters was observed, indicating a dominant combined influence of climate and water availability. This enabled discrimination between sesame samples from tropical and subtropical/moderate climatic provenances. Carbon isotope values also showed differences between oil from black and white sesame seeds from identical locations, indicating higher water use efficiency of plants producing black seeds. DNA based markers gave independent evidence for geographic variation as well as provided information on the genetic relatedness of the investigated samples. Depending on the differences in ambient environmental conditions and in the genotypic fingerprint, a combination of both analytical methods is a very powerful tool to assess the declared geographic origin. To our knowledge this is the first paper on food authenticity combining the stable isotope analysis of bio-elements with DNA based markers and their combined statistical analysis. PMID:25831054

Inbreeding and outbreeding depression in Stylidium hispidum: implications for mixing seed sources for ecological restoration

PubMed Central

Hufford, Kristina M; Krauss, Siegfried L; Veneklaas, Erik J

2012-01-01

The benefits of composite rather than local seed provenances for ecological restoration have recently been argued, largely on the basis of maximizing evolutionary potential. However, these arguments have downplayed the potentially negative consequences of outbreeding depression once mixed provenances interbreed. In this study, we compared intraspecific F1 hybrid performance and molecular marker differentiation among four populations of Stylidium hispidum, a species endemic to Southwestern Australia. Multivariate ordination of 134 AFLP markers analyzed genetic structure and detected two clusters of paired sites that diverged significantly for marker variation along a latitudinal boundary. To test for outbreeding depression and to determine the consequences of molecular population divergence for hybrid fitness, we conducted controlled pollinations and studied germination and survival for three cross categories (within-population crosses, short- and long-distance F1 hybrids) for paired sites distributed within and between the two genetically differentiated regions. We found evidence of outbreeding depression in long-distance hybrids (111–124 km), and inbreeding depression among progeny of within-population crosses, relative to short-distance (3–10 km) hybrids, suggesting an intermediate optimal outcrossing distance in this species. These results are discussed in light of the evolutionary consequences of mixing seed sources for biodiversity restoration. PMID:23139884

Mass Spectrometry Imaging proves differential absorption profiles of well-characterised permeability markers along the crypt-villus axis.

PubMed

Nilsson, Anna; Peric, Alexandra; Strimfors, Marie; Goodwin, Richard J A; Hayes, Martin A; Andrén, Per E; Hilgendorf, Constanze

2017-07-25

Knowledge about the region-specific absorption profiles from the gastrointestinal tract of orally administered drugs is a critical factor guiding dosage form selection in drug development. We have used a novel approach to study three well-characterized permeability and absorption marker drugs in the intestine. Propranolol and metoprolol (highly permeable compounds) and atenolol (low-moderate permeability compound) were orally co-administered to rats. The site of drug absorption was revealed by high spatial resolution matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) and complemented by quantitative measurement of drug concentration in tissue homogenates. MALDI-MSI identified endogenous molecular markers that illustrated the villi structures and confirmed the different absorption sites assigned to histological landmarks for the three drugs. Propranolol and metoprolol showed a rapid absorption and shorter transit distance in contrast to atenolol, which was absorbed more slowly from more distal sites. This study provides novel insights into site specific absorption for each of the compounds along the crypt-villus axis, as well as confirming a proximal-distal absorption gradient along the intestine. The combined analytical approach allowed the quantification and spatial resolution of drug distribution in the intestine and provided experimental evidence for the suggested absorption behaviour of low and highly permeable compounds.

CD200 is a useful diagnostic marker for identifying atypical chronic lymphocytic leukemia by flow cytometry.

PubMed

Ting, Y S; Smith, S A B C; Brown, D A; Dodds, A J; Fay, K C; Ma, D D F; Milliken, S; Moore, J J; Sewell, W A

2018-05-27

Immunophenotyping by flow cytometry is routinely employed in distinguishing between chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). Inclusion of CD200 has been reported to contribute to more reliable differentiation between CLL and MCL. We investigated the value of CD200 in assessment of atypical CLL cases. CD200 expression on mature B cell neoplasms was studied by eight-color flow cytometry in combination with a conventional panel of flow cytometry markers. The study included 70 control samples, 63 samples with CLL or atypical CLL phenotype, 6 MCL samples, and 40 samples of other mature B cell neoplasms. All CLL samples were positive for CD200, whereas MCL samples were dim or negative for CD200. Of the CLL samples, 7 were atypical by conventional flow cytometry, with Matutes scores ≤3. These cases were tested for evidence of a t(11;14) translocation, characteristic of MCL, and all were negative, consistent with their classification as atypical CLL. All these atypical CLL samples were strongly positive for CD200. CD200 proved to be a useful marker for differentiation between CLL and MCL by flow cytometry. In particular, CD200 was useful in distinguishing CLL samples with atypical immunophenotypes from MCL. © 2018 John Wiley & Sons Ltd.

A high-resolution cat radiation hybrid and integrated FISH mapping resource for phylogenomic studies across Felidae.

PubMed

Davis, Brian W; Raudsepp, Terje; Pearks Wilkerson, Alison J; Agarwala, Richa; Schäffer, Alejandro A; Houck, Marlys; Chowdhary, Bhanu P; Murphy, William J

2009-04-01

We describe the construction of a high-resolution radiation hybrid (RH) map of the domestic cat genome, which includes 2662 markers, translating to an estimated average intermarker distance of 939 kilobases (kb). Targeted marker selection utilized the recent feline 1.9x genome assembly, concentrating on regions of low marker density on feline autosomes and the X chromosome, in addition to regions flanking interspecies chromosomal breakpoints. Average gap (breakpoint) size between cat-human ordered conserved segments is less than 900 kb. The map was used for a fine-scale comparison of conserved syntenic blocks with the human and canine genomes. Corroborative fluorescence in situ hybridization (FISH) data were generated using 129 domestic cat BAC clones as probes, providing independent confirmation of the long-range correctness of the map. Cross-species hybridization of BAC probes on divergent felids from the genera Profelis (serval) and Panthera (snow leopard) provides further evidence for karyotypic conservation within felids, and demonstrates the utility of such probes for future studies of chromosome evolution within the cat family and in related carnivores. The integrated map constitutes a comprehensive framework for identifying genes controlling feline phenotypes of interest, and to aid in assembly of a higher coverage feline genome sequence.

A High-Resolution Cat Radiation Hybrid and Integrated FISH Mapping Resource for Phylogenomic Studies across Felidae

PubMed Central

Davis, Brian W.; Raudsepp, Terje; Wilkerson, Alison J. Pearks; Agarwala, Richa; Schäffer, Alejandro A.; Houck, Marlys; Ryder, Oliver A.; Chowdhdary, Bhanu P.; Murphy, William J.

2008-01-01

We describe the construction of a high-resolution radiation hybrid (RH) map of the domestic cat genome, which includes 2,662 markers, translating to an estimated average intermarker distance of 939 kilobases (Kb). Targeted marker selection utilized the recent feline 1.9x genome assembly, concentrating on regions of low marker density on feline autosomes and the X chromosome, in addition to regions flanking interspecies chromosomal breakpoints. Average gap (breakpoint) size between cat-human ordered conserved segments is less than 900 Kb. The map was used for a fine-scale comparison of conserved syntenic blocks with the human and canine genomes. Corroborative fluorescence in situ hybridization (FISH) data were generated using 129 domestic cat BAC-clones as probes, providing independent confirmation of the long-range correctness of the map. Cross-species hybridization of BAC probes on divergent felids from the genera Profelis (serval) and Panthera (snow leopard) provides further evidence for karyotypic conservation within felids, and demonstrates the utility of such probes for future studies of chromosome evolution within the cat family and in related carnivores. The integrated map constitutes a comprehensive framework for identifying genes controlling feline phenotypes of interest, and to aid in assembly of a higher coverage feline genome sequence. PMID:18951970

An fMRI Study of Grammatical Morpheme Processing Associated with Nouns and Verbs in Chinese

PubMed Central

Yu, Xi; Bi, Yanchao; Han, Zaizhu; Law, Sam-Po

2013-01-01

This study examined whether the degree of complexity of a grammatical component in a language would impact on its representation in the brain through identifying the neural correlates of grammatical morpheme processing associated with nouns and verbs in Chinese. In particular, the processing of Chinese nominal classifiers and verbal aspect markers were investigated in a sentence completion task and a grammaticality judgment task to look for converging evidence. The Chinese language constitutes a special case because it has no inflectional morphology per se and a larger classifier than aspect marker inventory, contrary to the pattern of greater verbal than nominal paradigmatic complexity in most European languages. The functional imaging results showed BA47 and left supplementary motor area and superior medial frontal gyrus more strongly activated for classifier processing, and the left posterior middle temporal gyrus more responsive to aspect marker processing. We attributed the activation in the left prefrontal cortex to greater processing complexity during classifier selection, analogous to the accounts put forth for European languages, and the left posterior middle temporal gyrus to more demanding verb semantic processing. The overall findings significantly contribute to cross-linguistic observations of neural substrates underlying processing of grammatical morphemes from an analytic and a classifier language, and thereby deepen our understanding of neurobiology of human language. PMID:24146745

Stromatolites in the approximately 3400 Ma Strelley Pool Formation, Western Australia: examining biogenicity from the macro- to the nano-scale.

PubMed

Wacey, David

2010-05-01

The 3426-3350 Ma Strelley Pool Formation (SPF) is a silicified, dominantly sedimentary unit within the Pilbara Supergroup, Western Australia. It is found widely across the East Pilbara Terrane, and it forms a prominent marker horizon and separates the largely volcanic 3520-3427 Ma Warrawoona and 3350-3315 Ma Kelly groups. It has become one of the key formations for study by astrobiologists, following reports of some of the world's oldest stromatolites. Abundant contextural and morphological evidence has been presented over the last decade in support of a biological role in SPF stromatolite formation. This evidence is reviewed here, and additional data are presented from recent fieldwork carried out across the approximately 25 km of SPF outcrops in the East Strelley greenstone belt of the East Pilbara Terrane. In addition to contextural and morphological evidence, a compelling claim for early life requires geochemical evidence for biological cycling. A potential avenue of approach to obtain such evidence for the SPF stromatolites (and other ancient examples) is discussed in the context of a pilot study in which nano-scale secondary ion mass spectrometry (NanoSIMS) was used.

Pheno2Geno - High-throughput generation of genetic markers and maps from molecular phenotypes for crosses between inbred strains.

PubMed

Zych, Konrad; Li, Yang; van der Velde, Joeri K; Joosen, Ronny V L; Ligterink, Wilco; Jansen, Ritsert C; Arends, Danny

2015-02-19

Genetic markers and maps are instrumental in quantitative trait locus (QTL) mapping in segregating populations. The resolution of QTL localization depends on the number of informative recombinations in the population and how well they are tagged by markers. Larger populations and denser marker maps are better for detecting and locating QTLs. Marker maps that are initially too sparse can be saturated or derived de novo from high-throughput omics data, (e.g. gene expression, protein or metabolite abundance). If these molecular phenotypes are affected by genetic variation due to a major QTL they will show a clear multimodal distribution. Using this information, phenotypes can be converted into genetic markers. The Pheno2Geno tool uses mixture modeling to select phenotypes and transform them into genetic markers suitable for construction and/or saturation of a genetic map. Pheno2Geno excludes candidate genetic markers that show evidence for multiple possibly epistatically interacting QTL and/or interaction with the environment, in order to provide a set of robust markers for follow-up QTL mapping. We demonstrate the use of Pheno2Geno on gene expression data of 370,000 probes in 148 A. thaliana recombinant inbred lines. Pheno2Geno is able to saturate the existing genetic map, decreasing the average distance between markers from 7.1 cM to 0.89 cM, close to the theoretical limit of 0.68 cM (with 148 individuals we expect a recombination every 100/148=0.68 cM); this pinpointed almost all of the informative recombinations in the population. The Pheno2Geno package makes use of genome-wide molecular profiling and provides a tool for high-throughput de novo map construction and saturation of existing genetic maps. Processing of the showcase dataset takes less than 30 minutes on an average desktop PC. Pheno2Geno improves QTL mapping results at no additional laboratory cost and with minimum computational effort. Its results are formatted for direct use in R/qtl, the leading R package for QTL studies. Pheno2Geno is freely available on CRAN under "GNU GPL v3". The Pheno2Geno package as well as the tutorial can also be found at: http://pheno2geno.nl .

Cathepsin K expression in a wide spectrum of perivascular epithelioid cell neoplasms (PEComas): a clinicopathological study emphasizing extrarenal PEComas.

PubMed

Rao, Qiu; Cheng, Liang; Xia, Qiu-yuan; Liu, Biao; Li, Li; Shi, Qun-li; Shi, Shan-shan; Yu, Bo; Zhang, Ru-song; Ma, Heng-hui; Lu, Zhen-feng; Tu, Pin; Zhou, Xiao-jun

2013-03-01

Recent studies have demonstrated that cathepsin K seems to be a powerful marker in identifying renal perivascular epithelioid cell neoplasms (PEComas). However, the expression in extrarenal PEComas has not been well characterized due to their rare incidence. Our aim was to investigate the expression of cathepsin K in a wide spectrum of extrarenal PEComas and evaluate its potential diagnostic usefulness in comparison with other commonly used markers. Twenty-three cases of PEComa (liver, n = 9; lung, n = 1; broad ligament of uterus, n = 1; vertex subcutaneous soft tissue, n = 1; abdominal wall, n = 1; and kidney, n = 10) were selected for study. All displayed a high percentage of cells with moderately to strongly positive reactions for cathepsin K (mean 91%; range 80-100%). HMB45, Melan-A and smooth muscle actin (SMA) were expressed in 78, 87 and 87% of cases, respectively, with various percentages of positive cells (mean, 34, 40 and 38%; range 0-80, 0-90 and 0-90%). Transcription factor E3 (TFE3) was expressed strongly in only three cases; none exhibited evidence of TFE3 gene fusion or amplification. Cathepsin K appears to be more powerful than other commonly used markers in diagnosing a wide spectrum of PEComas and distinguishing them from the majority of human cancers. © 2012 Blackwell Publishing Ltd.

Elevated serum adipsin may predict unsuccessful treatment for cows' milk allergy but other biomarkers do not.

PubMed

Salmivesi, Susanna; Paassilta, Marita; Huhtala, Heini; Nieminen, Riina; Moilanen, Eeva; Korppi, Matti

2018-02-01

This study evaluated whether 15 allergy, immunology or inflammatory markers predicted the long-term use of cows' milk or milk products seven years after the start of oral immunotherapy (OIT) for cows' milk allergy in children. The following laboratory parameters were measured before the OIT at Tampere University Hospital, Finland, and after the six-month escalation phase: serum total immunoglobulin (Ig) E, milk-specific IgG and IgG4, eosinophil cationic protein, eosinophil-derived neurotoxin, interleukins 4, 5, 6, 10 and 12p70 and serum adipokines adiponectin, adipsin, leptin and resistin. Follow-up data from a seven-year phone questionnaire in 2015 were available for 24 children: 14 successful and 10 unsuccessful milk users. There were no significant differences in any of the 15 markers measured at the start of the study between the subjects who later formed the successful and unsuccessful groups. At the end of the six-month escalation phase of OIT, serum adipsin was higher in the group who were unsuccessful milk users at the seven-year follow-up study. None of the 15 allergy, immunology or inflammatory markers were useful in predicting the outcome of OIT. Preliminary evidence was found that high serum adipsin after the six-month escalation phase of OIT might predict unsuccessful outcome. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Coffee and tea consumption in relation to inflammation and basal glucose metabolism in a multi-ethnic Asian population: a cross-sectional study.

PubMed

Rebello, Salome A; Chen, Cynthia H; Naidoo, Nasheen; Xu, Wang; Lee, Jeannette; Chia, Kee Seng; Tai, E Shyong; van Dam, Rob M

2011-06-02

Higher coffee consumption has been associated with a lower risk of type 2 diabetes in cohort studies, but the physiological pathways through which coffee affects glucose metabolism are not fully understood. The aim of this study was to evaluate the associations between habitual coffee and tea consumption and glucose metabolism in a multi-ethnic Asian population and possible mediation by inflammation. We cross-sectionally examined the association between coffee, green tea, black tea and Oolong tea consumption and glycemic (fasting plasma glucose, HOMA-IR, HOMA-beta, plasma HbA1c) and inflammatory (plasma adiponectin and C-reactive protein) markers in a multi-ethnic Asian population (N = 4139). After adjusting for multiple confounders, we observed inverse associations between coffee and HOMA-IR (percent difference: - 8.8% for ≥ 3 cups/day versus rarely or never; Ptrend = 0.007), but no significant associations between coffee and inflammatory markers. Tea consumption was not associated with glycemic markers, but green tea was inversely associated with plasma C-reactive protein concentrations (percent difference: - 12.2% for ≥ 1 cup/day versus < 1 cup/week; Ptrend = 0.042). These data provide additional evidence for a beneficial effect of habitual caffeinated coffee consumption on insulin sensitivity, and suggest that this effect is unlikely to be mediated by anti-inflammatory mechanisms.

Evidence to support including lifestyle light-intensity recommendations in physical activity guidelines for older adults.

PubMed

Loprinzi, Paul D; Lee, Hyo; Cardinal, Bradley J

2015-01-01

The purpose of this study was to examine the association of objectively measured lifestyle light-intensity physical activity (LLPA) and moderate-to-vigorous physical activity (MVPA) with various biological markers and chronic diseases among a nationally representative sample of U.S. older adults (65+ years). A cross-sectional design was used for this study. Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2003-2006. Subjects were 1,496 older U.S. adults. Participants wore an accelerometer for at least 4 days and completed questionnaires to assess sociodemographics and chronic disease information. Blood samples were taken to assess biological markers. Adjusted Wald tests and Poisson regression were used to examine the association of LLPA and MVPA with biological markers and chronic disease. Older adults engaging in ≥300 min/wk of LLPA had lower observed values for body mass index, waist circumference, C-reactive protein, and insulin resistance compared to those engaging in <300 min/wk of LLPA. Additionally, those engaging in <300 min/wk of LLPA had a rate 1.18 times greater for having chronic disease compared to those engaging in ≥300 min/wk of LLPA. In this national sample of older U.S. adults, participation in at least 300 min/wk of LLPA was associated with more favorable health outcomes. Future experimental studies are warranted to confirm these findings.

Mouse Retinal Pigmented Epithelial Cell Lines retain their phenotypic characteristics after transfection with Human Papilloma Virus: A new tool to further the study of RPE biology

PubMed Central

Catanuto, Paola; Espinosa-Heidmann, Diego; Pereira-Simon, Simone; Sanchez, Patricia; Salas, Pedro; Hernandez, Eleut; Cousins, Scott W.; Elliot, Sharon J.

2009-01-01

Development of immortalized mouse retinal pigmented epithelial cell (RPE) lines that retain many of their in vivo phenotypic characteristics, would aid in studies of ocular diseases including age related macular degeneration (AMD). RPE cells were isolated from 16 month old (estrogen receptor knockout) ERKOα and ERKOβ mice and their C57Bl/6 wild type littermates. RPE65 and cellular retinaldehyde binding protein (CRALBP) expression, in vivo markers of RPE cells, were detected by real-time RT-PCR and western analysis. We confirmed the presence of epithelial cell markers, ZO1, cytokeratin 8 and 18 by immunofluorescence staining. In addition, we confirmed the distribution of actin filaments and the expression of ezrin. To develop cell lines, RPE cells were isolated, propagated and immortalized using human papilloma virus (HPV) 16 (E6/E7). RPE-specific markers and morphology were assessed before and after immortalization. In wildtype littermate controls, there was no evidence of any alterations in the parameters that we examined including MMP-2, TIMP-2, collagen type IV, and estrogen receptor (ER) α and ERβ protein expression and ER copy number ratio. Therefore, immortalized mouse RPE cell lines that retain their in vivo phenotype can be isolated from either pharmacologically or genetically manipulated mice, and may be used to study RPE cell biology. PMID:19013153

Coffee and tea consumption in relation to inflammation and basal glucose metabolism in a multi-ethnic Asian population: a cross-sectional study

PubMed Central

2011-01-01

Background Higher coffee consumption has been associated with a lower risk of type 2 diabetes in cohort studies, but the physiological pathways through which coffee affects glucose metabolism are not fully understood. The aim of this study was to evaluate the associations between habitual coffee and tea consumption and glucose metabolism in a multi-ethnic Asian population and possible mediation by inflammation. Methods We cross-sectionally examined the association between coffee, green tea, black tea and Oolong tea consumption and glycemic (fasting plasma glucose, HOMA-IR, HOMA-beta, plasma HbA1c) and inflammatory (plasma adiponectin and C-reactive protein) markers in a multi-ethnic Asian population (N = 4139). Results After adjusting for multiple confounders, we observed inverse associations between coffee and HOMA-IR (percent difference: - 8.8% for ≥ 3 cups/day versus rarely or never; Ptrend = 0.007), but no significant associations between coffee and inflammatory markers. Tea consumption was not associated with glycemic markers, but green tea was inversely associated with plasma C-reactive protein concentrations (percent difference: - 12.2% for ≥ 1 cup/day versus < 1 cup/week; Ptrend = 0.042). Conclusions These data provide additional evidence for a beneficial effect of habitual caffeinated coffee consumption on insulin sensitivity, and suggest that this effect is unlikely to be mediated by anti-inflammatory mechanisms. PMID:21631956

Attachment narratives in refugee children: interrater reliability and qualitative analysis in pilot findings from a two-site study.

PubMed

De Haene, Lucia; Dalgaard, Nina Thorup; Montgomery, Edith; Grietens, Hans; Verschueren, Karine

2013-06-01

Although forced migration research on refugee family functioning clearly points to the potential breakdown of parental availability and responsiveness in the context of cumulative migration stressors, studies exploring attachment security in refugee children are surprisingly lacking so far. The authors report their findings from a 2-site, small-scale administration of an attachment measure, adapted for use with refugee children aged between 4 and 9 years from a reliable and validated doll-play procedure. We evaluated interrater reliability and conducted a qualitative analysis of refugee children's narrative response to identify migration-specific representational markers of attachment quality. The level of agreement among 3 independent coders ranged between .54 to 1.00 for both study samples, providing initial psychometric evidence of the measure's value in assessing child attachment security in this population. The exploratory analysis of migration-related narrative markers pointed to specific parameters to be used in parent-child observational assessments in future validation of the attachment measure, such as parental withdrawal or trauma-communication within the parent-child dyad. Copyright © 2013 International Society for Traumatic Stress Studies.

Population genomics of the inbred Scandinavian wolf.

PubMed

Hagenblad, Jenny; Olsson, Maria; Parker, Heidi G; Ostrander, Elaine A; Ellegren, Hans

2009-04-01

The Scandinavian wolf population represents one of the genetically most well-characterized examples of a severely bottlenecked natural population (with only two founders), and of how the addition of new genetic material (one immigrant) can at least temporarily provide a 'genetic rescue'. However, inbreeding depression has been observed in this population and in the absence of additional immigrants, its long-term viability is questioned. To study the effects of inbreeding and selection on genomic diversity, we performed a genomic scan with approximately 250 microsatellite markers distributed across all autosomes and the X chromosome. We found linkage disequilibrium (LD) that extended up to distances of 50 Mb, exceeding that of most outbreeding species studied thus far. LD was particularly pronounced on the X chromosome. Overall levels of observed genomic heterozygosity did not deviate significantly from simulations based on known population history, giving no support for a general selection for heterozygotes. However, we found evidence supporting balancing selection at a number of loci and also evidence suggesting directional selection at other loci. For markers on chromosome 23, the signal of selection was particularly strong, indicating that purifying selection against deleterious alleles may have occurred even in this very small population. These data suggest that population genomics allows the exploration of the effects of neutral and non-neutral evolution on a finer scale than what has previously been possible.

Pharmacokinetic study of Noni fruit extract.

PubMed

Issell, Brian F; Franke, Adrian; Fielding, Robert M

2008-01-01

Many different products containing Noni (Morinda citrifolia) fruit extracts are sold throughout the world for health restoration and maintenance. Despite a large business enterprise fueling Noni's popularity, there is a lack of standardization of products and no scientific evidence of Noni's clinical efficacy and safety. There is also no evidence to indicate an optimal therapeutic dose or dosing interval. In an initial volunteer, scopoletin was identified as a bioactive marker of Noni exposure and a candidate for product standardization and pharmacokinetic studies. Subsequently, capsules containing the whole freeze-dried fruit of Noni were orally administered to nine healthy volunteers (3 per group) at doses of 1,500 mg (3 × 500 mg), 2,000 mg (4 × 500 mg) and 2,500 mg (5 × 500 mg). Plasma and urine samples were obtained from each subject prior to dosing and at 0.5, 1, 2, 4 and 8 h after dosing. Concentrations of scopoletin were determined by HPLC with PDA (scanning at 200-700 nm) and MS detection. Scopoletin rapidly enters the plasma after Noni ingestion, maintaining levels in the range of 0.5 to 5 ng/mL for at least 8 h after dosing. Scopoletin bioavailability appears to be low, with significant intersubject variability. We conclude that scopoletin can be used as a relatively specific marker of Noni exposure in the blood and particularly in urine when its pharmacokinetics is considered appropriately.

Age- and Sex-Specific Causal Effects of Adiposity on Cardiovascular Risk Factors

PubMed Central

Fall, Tove; Hägg, Sara; Ploner, Alexander; Mägi, Reedik; Fischer, Krista; Draisma, Harmen H.M.; Sarin, Antti-Pekka; Benyamin, Beben; Ladenvall, Claes; Åkerlund, Mikael; Kals, Mart; Esko, Tõnu; Nelson, Christopher P.; Kaakinen, Marika; Huikari, Ville; Mangino, Massimo; Meirhaeghe, Aline; Kristiansson, Kati; Nuotio, Marja-Liisa; Kobl, Michael; Grallert, Harald; Dehghan, Abbas; Kuningas, Maris; de Vries, Paul S.; de Bruijn, Renée F.A.G.; Willems, Sara M.; Heikkilä, Kauko; Silventoinen, Karri; Pietiläinen, Kirsi H.; Legry, Vanessa; Giedraitis, Vilmantas; Goumidi, Louisa; Syvänen, Ann-Christine; Strauch, Konstantin; Koenig, Wolfgang; Lichtner, Peter; Herder, Christian; Palotie, Aarno; Menni, Cristina; Uitterlinden, André G.; Kuulasmaa, Kari; Havulinna, Aki S.; Moreno, Luis A.; Gonzalez-Gross, Marcela; Evans, Alun; Tregouet, David-Alexandre; Yarnell, John W.G.; Virtamo, Jarmo; Ferrières, Jean; Veronesi, Giovanni; Perola, Markus; Arveiler, Dominique; Brambilla, Paolo; Lind, Lars; Kaprio, Jaakko; Hofman, Albert; Stricker, Bruno H.; van Duijn, Cornelia M.; Ikram, M. Arfan; Franco, Oscar H.; Cottel, Dominique; Dallongeville, Jean; Hall, Alistair S.; Jula, Antti; Tobin, Martin D.; Penninx, Brenda W.; Peters, Annette; Gieger, Christian; Samani, Nilesh J.; Montgomery, Grant W.; Whitfield, John B.; Martin, Nicholas G.; Groop, Leif; Spector, Tim D.; Magnusson, Patrik K.; Amouyel, Philippe; Boomsma, Dorret I.; Nilsson, Peter M.; Järvelin, Marjo-Riitta; Lyssenko, Valeriya; Metspalu, Andres; Strachan, David P.; Salomaa, Veikko; Ripatti, Samuli; Pedersen, Nancy L.; Prokopenko, Inga; McCarthy, Mark I.

2015-01-01

Observational studies have reported different effects of adiposity on cardiovascular risk factors across age and sex. Since cardiovascular risk factors are enriched in obese individuals, it has not been easy to dissect the effects of adiposity from those of other risk factors. We used a Mendelian randomization approach, applying a set of 32 genetic markers to estimate the causal effect of adiposity on blood pressure, glycemic indices, circulating lipid levels, and markers of inflammation and liver disease in up to 67,553 individuals. All analyses were stratified by age (cutoff 55 years of age) and sex. The genetic score was associated with BMI in both nonstratified analysis (P = 2.8 × 10−107) and stratified analyses (all P < 3.3 × 10−30). We found evidence of a causal effect of adiposity on blood pressure, fasting levels of insulin, C-reactive protein, interleukin-6, HDL cholesterol, and triglycerides in a nonstratified analysis and in the <55-year stratum. Further, we found evidence of a smaller causal effect on total cholesterol (P for difference = 0.015) in the ≥55-year stratum than in the <55-year stratum, a finding that could be explained by biology, survival bias, or differential medication. In conclusion, this study extends previous knowledge of the effects of adiposity by providing sex- and age-specific causal estimates on cardiovascular risk factors. PMID:25712996

Rethinking dry eye disease: a perspective on clinical implications.

PubMed

Bron, Anthony J; Tomlinson, Alan; Foulks, Gary N; Pepose, Jay S; Baudouin, Christophe; Geerling, Gerd; Nichols, Kelly K; Lemp, Michael A

2014-04-01

Publication of the DEWS report in 2007 established the state of the science of dry eye disease (DED). Since that time, new evidence suggests that a rethinking of traditional concepts of dry eye disease is in order. Specifically, new evidence on the epidemiology of the disease, as well as strategies for diagnosis, have changed the understanding of DED, which is a heterogeneous disease associated with considerable variability in presentation. These advances, along with implications for clinical care, are summarized herein. The most widely used signs of DED are poorly correlated with each other and with symptoms. While symptoms are thought to be characteristic of DED, recent studies have shown that less than 60% of subjects with other objective evidence of DED are symptomatic. Thus the use of symptoms alone in diagnosis will likely result in missing a significant percentage of DED patients, particularly with early/mild disease. This could have considerable impact in patients undergoing cataract or refractive surgery as patients with DED have less than optimal visual results. The most widely used objective signs for diagnosing DED all show greater variability between eyes and in the same eye over time compared with normal subjects. This variability is thought to be a manifestation of tear film instability which results in rapid breakup of the tearfilm between blinks and is an identifier of patients with DED. This feature emphasizes the bilateral nature of the disease in most subjects not suffering from unilateral lid or other unilateral destabilizing surface disorders. Instability of the composition of the tears also occurs in dry eye disease and shows the same variance between eyes. Finally, elevated tear osmolarity has been reported to be a global marker (present in both subtypes of the disease- aqueous-deficient dry eye and evaporative dry eye). Clinically, osmolarity has been shown to be the best single metric for diagnosis of DED and is directly related to increasing severity of disease. Clinical examination and other assessments differentiate which subtype of disease is present. With effective treatment, the tear osmolarity returns to normal, and its variability between eyes and with time disappears. Other promising markers include objective measures of visual deficits, proinflammatory molecular markers and other molecular markers, specific to each disease subtype, and panels of tear proteins. As yet, however, no single protein or panel of markers has been shown to discriminate between the major forms of DED. With the advent of new tests and technology, improved endpoints for clinical trials may be established, which in turn may allow new therapeutic agents to emerge in the foreseeable future. Accurate recognition of disease is now possible and successful management of DED appears to be within our grasp, for a majority of our patients. Copyright © 2014 Elsevier Inc. All rights reserved.

The Interplay Between Fiber and the Intestinal Microbiome in the Inflammatory Response12

PubMed Central

Kuo, Shiu-Ming

2013-01-01

Fiber intake is critical for optimal health. This review covers the anti-inflammatory roles of fibers using results from human epidemiological observations, clinical trials, and animal studies. Fiber has body weight–related anti-inflammatory activity. With its lower energy density, a diet high in fiber has been linked to lower body weight, alleviating obesity-induced chronic inflammation evidenced by reduced amounts of inflammatory markers in human and animal studies. Body weight–unrelated anti-inflammatory activity of fiber has also been extensively studied in animal models in which the type and amount of fiber intake can be closely monitored. Fermentable fructose-, glucose-, and galactose-based fibers as well as mixed fibers have shown systemic and local intestinal anti-inflammatory activities when plasma inflammatory markers and tissue inflammation were examined. Similar anti-inflammatory activities have also been demonstrated in some human studies that controlled total fiber intake. The anti-inflammatory activities of synbiotics (probiotics plus fiber) were reviewed as well, but there was no convincing evidence indicating higher efficacy of synbiotics compared with that of fiber alone. Adverse effects have not been observed with the amount of fiber intake or supplementation used in studies, although patients with Crohn’s disease may be more sensitive to inulin intake. Several possible mechanisms that may mediate the body weight–unrelated anti-inflammatory activity of fibers are discussed based on the in vitro and in vivo evidence. Fermentable fibers are known to affect the intestinal microbiome. The immunomodulatory role of the intestinal microbiome and/or microbial metabolites could contribute to the systemic and local anti-inflammatory activities of fibers. PMID:23319119

Nestin-expressing cells in the pancreatic islets of Langerhans.

PubMed

Hunziker, E; Stein, M

2000-04-29

The pancreatic islets of Langerhans produce several peptide hormones, predominantly the metabolically active hormones insulin and glucagon, which are critical for maintaining normal fuel homeostasis. Some evidence exists that pancreatic endocrine cells turn over at a slow rate and can regenerate in certain conditions. This could be due to the presence of pluripotent cells residing in the pancreas. Recently the intermediate filament protein nestin has been identified to be a marker for a multipotent stem cell in the central nervous system. Given the similarity between the pancreatic islets and neuronal cells, we hypothesized that stem cells expressing nestin might be present in the pancreas. Here we present evidence that a subset of cells in the pancreatic islets express the stem cell marker nestin. These cells might serve as precursors of differentiated pancreatic endocrine cells. Copyright 2000 Academic Press.

Towards microbial fermentation metabolites as markers for health benefits of prebiotics.

PubMed

Verbeke, Kristin A; Boobis, Alan R; Chiodini, Alessandro; Edwards, Christine A; Franck, Anne; Kleerebezem, Michiel; Nauta, Arjen; Raes, Jeroen; van Tol, Eric A F; Tuohy, Kieran M

2015-06-01

Available evidence on the bioactive, nutritional and putative detrimental properties of gut microbial metabolites has been evaluated to support a more integrated view of how prebiotics might affect host health throughout life. The present literature inventory targeted evidence for the physiological and nutritional effects of metabolites, for example, SCFA, the potential toxicity of other metabolites and attempted to determine normal concentration ranges. Furthermore, the biological relevance of more holistic approaches like faecal water toxicity assays and metabolomics and the limitations of faecal measurements were addressed. Existing literature indicates that protein fermentation metabolites (phenol, p-cresol, indole, ammonia), typically considered as potentially harmful, occur at concentration ranges in the colon such that no toxic effects are expected either locally or following systemic absorption. The endproducts of saccharolytic fermentation, SCFA, may have effects on colonic health, host physiology, immunity, lipid and protein metabolism and appetite control. However, measuring SCFA concentrations in faeces is insufficient to assess the dynamic processes of their nutrikinetics. Existing literature on the usefulness of faecal water toxicity measures as indicators of cancer risk seems limited. In conclusion, at present there is insufficient evidence to use changes in faecal bacterial metabolite concentrations as markers of prebiotic effectiveness. Integration of results from metabolomics and metagenomics holds promise for understanding the health implications of prebiotic microbiome modulation but adequate tools for data integration and interpretation are currently lacking. Similarly, studies measuring metabolite fluxes in different body compartments to provide a more accurate picture of their nutrikinetics are needed.

Chemokines additional to IFN-γ can be used to differentiate among Mycobacterium tuberculosis infection possibilities and provide evidence of an early clearance phenotype.

PubMed

Nonghanphithak, Ditthawat; Reechaipichitkul, Wipa; Namwat, Wises; Naranbhai, Vivek; Faksri, Kiatichai

2017-07-01

Current diagnostic tests for tuberculosis (TB) remain limited in their ability to discriminate between active TB (ATB) and latent TB infection (LTBI). Early clearance (EC) of TB by individuals exposed to Mycobacterium tuberculosis is a debated phenomenon for which evidence is lacking. We measured and compared secreted chemokines in the plasma fraction from 48 ATB, 38 LTBI, 162 presumed EC and 39 healthy controls (HC) using the QuantiFERON ® -TB Gold In-Tube assay. Single chemokine markers were limited in their ability to discriminate between ATB and LTBI: IFN-γ showed 16.7% sensitivity; CCL2 showed moderate sensitivity (70.8%) and specificity (74.4%); CXCL10 showed high sensitivity (87.5%) and specificity (78.9%). Compared to IFN-γ alone, IFN-γ combined with CXCL10 significantly improved (p < 0.001) the sensitivity and specificity to discriminate between ATB and HC (97.9% sensitivity and 94.9% specificity) and between ATB and LTBI (89.6% sensitivity and 71.1% specificity). Levels of CCL2 were very significantly lower (p < 0.0001) in EC compared to HC groups and hence CCL2 is a useful marker for EC. This study demonstrated the potential application of profiling using multiple chemokines for differentiating among the various M. tuberculosis infection possibilities. We also present evidence to support the EC phenomenon based on the decrease of CCL2 levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Identification case of evidence in timber tracing of Pinus radiate, using high-resolution melting (HRM) analysis.

PubMed

Solano, Jaime; Anabalón, Leonardo; Encina, Francisco

2016-03-01

Fast, accurate detection of plant species and their hybrids using molecular tools will facilitate assessment and monitoring of timber tracing evidence. In this study the origin of unknown pine samples is determined for a case of timber theft in the region of Araucania southern Chile. We evaluate the utility of the trnL marker region for species identification applied to pine wood based on High Resolution Melting. This efficient tracing methods can be incorporated into forestry applications such as certification of origin. The object of this work was genotype identification using high-resolution melting (HRM) and trnL approaches for Pinus radiata (Don) in timber tracing evidence. Our results indicate that trnL is a very sensitive marker for delimiting species and HRM analysis was used successfully for genotyping Pinus samples for timber tracing purposes. Genotyping samples by HRM analysis with the trnL1 approach allowed us to differentiate two wood samples from the Pinaceae family: Pinus radiata (Don) and Pseudotsuga menziesii (Mirb.) Franco. The same approach with Pinus trnL wood was not able to discriminate between samples of Pinus radiata, indicating that the samples were genetically indistinguishable, possibly because they have the same genotype at this locus. Timber tracing with HRM analysis is expected to contribute to future forest certification schemes, control of illegal trading, and molecular traceability of Pinus spp. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Linkage of Wolfram syndrome to chromosome 4p16.1 and evidence for heterogeneity

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

Collier, D.A.; Curtis, D.; Arranz, M.J.

1996-10-01

Wolfram syndrome (DIDMOAD syndrome; MIM 222300) is an autosomal recessive neurodegenerative disorder characterized by juvenile-onset diabetes mellitus and bilateral optic atrophy. Previous linkage analysis of multiply affected families indicated that the gene for Wolfram syndrome is on chromosome 4p, and it produced no evidence for locus heterogeneity. We have investigated 12 U.K. families with Wolfram syndrome, and we report confirmation of linkage to chromosome 4p, with a maximum two-point LOD score of 4.6 with DRD5, assuming homogeneity, and of 5.1, assuming heterogeneity. Overlapping multipoint analysis using six markers at a time produced definite evidence for locus heterogeneity: the maximum multipointmore » LOD score under homogeneity was <2, whereas when heterogeneity was allowed for an admixture a LOD of 6.2 was obtained in the interval between D4S432 and D4S431, with the peak close to the marker D4S3023. One family with an atypical phenotype was definitely unlinked to the region. Haplotype inspection of the remaining 11 families, which appear linked to chromosome 4p and had typical phenotypes, revealed crossover events during meiosis, which also placed the gene in the interval D4S432 and D4S431. In these families no recombinants were detected with the marker D4S3023, which maps within the same interval. 22 refs., 3 figs., 2 tabs.« less

Role of T cell receptor delta gene in susceptibility to celiac disease.

PubMed

Roschmann, E; Wienker, T F; Volk, B A

1996-02-01

There is a strong genetic influence on the susceptibility to celiac disease. Although in the vast majority of patients with celiac disease, the HLA-DQ(alpha1*0501, beta1*0201) heterodimer encoded by the alleles HLA-DQA1*0501 and HLA-DQB1*0201 seems to confer the primary disease susceptibility, it cannot be excluded that other genes contribute to disease susceptibility, as indicated by the difference in concordance rates between monozygotic twins and HLA identical siblings (70% vs. 30%). Obviously other genes involved in the genetic control of T cell mediated immune response could potentially influence susceptibility to celiac disease. The density of T cells using the gammadelta T cell receptor (TCR) is considerably increased in the jejunal epithelium of patients with celiac disease, an abnormality considered to be specific for celiac disease. This suggests an involvement of gammadelta T cells in the pathogenesis of the disease. To ascertain whether the TCR delta (TCRD) gene contributes to celiac disease susceptibility we carried out an association study and genetic linkage analysis using a highly polymorphic microsatellite marker at the TCRD locus on chromosome 14q11.2. The association study demonstrated no significant difference in allele frequencies of the TCRD gene marker between celiac disease patients and controls; accordingly, the relative risk estimates did not reach the level of statistical significance. In the linkage analysis, performed in 23 families, the logarithm of the odds (LOD) scores calculated for celiac disease versus the TCRD gene marker excluded linkage, suggesting that there is no determinant contributing to celiac disease status at or 5 cM distant to the analyzed TCRD gene marker. In conclusion, the results of the present study provide no evidence that the analyzed TCRD gene contributes substantially to celiac disease susceptibility.

Generation of Functional Lentoid Bodies From Human Induced Pluripotent Stem Cells Derived From Urinary Cells.

PubMed

Fu, Qiuli; Qin, Zhenwei; Jin, Xiuming; Zhang, Lifang; Chen, Zhijian; He, Jiliang; Ji, Junfeng; Yao, Ke

2017-01-01

The pathological mechanisms underlying cataract formation remain largely unknown on account of the lack of appropriate in vitro cellular models. The aim of this study is to develop a stable in vitro system for human lens regeneration using pluripotent stem cells. Isolated human urinary cells were infected with four Yamanaka factors to generate urinary human induced pluripotent stem cells (UiPSCs), which were induced to differentiate into lens progenitor cells and lentoid bodies (LBs). The expression of lens-specific markers was examined by real-time PCR, immunostaining, and Western blotting. The structure and magnifying ability of LBs were investigated using transmission electron microscopy and observing the magnification of the letter "X," respectively. We developed a "fried egg" differentiation method to generate functional LBs from UiPSCs. The UiPSC-derived LBs exhibited crystalline lens-like morphology and a transparent structure and expressed lens-specific markers αA-, αB-, β-, and γ-crystallin and MIP. During LB differentiation, the placodal markers SIX1, EYA1, DLX3, PAX6, and the specific early lens markers SOX1, PROX1, FOXE3, αA-, and αB-crystallin were observed at certain time points. Microscopic examination revealed the presence of lens epithelial cells adjacent to the lens capsule as well as both immature and mature fiber-like cells. Optical analysis further demonstrated the magnifying ability (1.7×) of the LBs generated from UiPSCs. Our study provides the first evidence toward generating functional LBs from UiPSCs, thereby establishing an in vitro system that can be used to study human lens development and cataractogenesis and perhaps even be useful for drug screening.

Cereal Crop Proteomics: Systemic Analysis of Crop Drought Stress Responses Towards Marker-Assisted Selection Breeding

PubMed Central

Ghatak, Arindam; Chaturvedi, Palak; Weckwerth, Wolfram

2017-01-01

Sustainable crop production is the major challenge in the current global climate change scenario. Drought stress is one of the most critical abiotic factors which negatively impact crop productivity. In recent years, knowledge about molecular regulation has been generated to understand drought stress responses. For example, information obtained by transcriptome analysis has enhanced our knowledge and facilitated the identification of candidate genes which can be utilized for plant breeding. On the other hand, it becomes more and more evident that the translational and post-translational machinery plays a major role in stress adaptation, especially for immediate molecular processes during stress adaptation. Therefore, it is essential to measure protein levels and post-translational protein modifications to reveal information about stress inducible signal perception and transduction, translational activity and induced protein levels. This information cannot be revealed by genomic or transcriptomic analysis. Eventually, these processes will provide more direct insight into stress perception then genetic markers and might build a complementary basis for future marker-assisted selection of drought resistance. In this review, we survey the role of proteomic studies to illustrate their applications in crop stress adaptation analysis with respect to productivity. Cereal crops such as wheat, rice, maize, barley, sorghum and pearl millet are discussed in detail. We provide a comprehensive and comparative overview of all detected protein changes involved in drought stress in these crops and have summarized existing knowledge into a proposed scheme of drought response. Based on a recent proteome study of pearl millet under drought stress we compare our findings with wheat proteomes and another recent study which defined genetic marker in pearl millet. PMID:28626463

Effects of Exercise on Select Biomarkers and Associated Outcomes in Chronic Pain Conditions: Systematic Review.

PubMed

Kawi, Jennifer; Lukkahatai, Nada; Inouye, Jillian; Thomason, Diane; Connelly, Kirsten

2016-03-01

Chronic pain is highly prevalent. Current management is challenged by lack of validated objective measures like biological markers. Clinical pain studies employing exercise interventions have evaluated biomarkers; however, it is unclear how exercise impacts biomarkers involved in pain pathways and whether these markers are associated with relevant pain-related outcomes. This systematic review evaluates data from clinical studies employing exercise interventions in chronic musculoskeletal nonmalignant pain conditions in which biomarkers in pain pathways were measured. Published research studies from several databases were examined using the Jadad Scale for assessing the quality of clinical studies. Twelve research studies were reviewed. Jadad scores ranged from 5 to 11 out of 13 points. Inflammatory markers were most commonly measured followed by neurotransmitter-related genes and metabolite-detecting genes. After exercise interventions, changes in biomarkers involved in neurotransmission and inflammation suggest a hypoalgesic exercise effect. Significant biomarker associations were found with pain intensity, fatigue, depression, anxiety, and quality of life. However, there were varying methodologies in the studies reviewed. It remains a question whether biomarkers can be used as objective measures for risk assessment, diagnosis, or evaluation or as surrogate endpoints in chronic pain. Adequate sample sizes, optimal exercise dose determination, study replications, and longitudinal research studies with consistent methodologies are warranted. Regardless, the potential translational value of biomarkers in chronic pain is evident. Advancing nursing research in biomarkers is vital for moving the nursing discipline and clinical chronic pain practice forward. Developing a biobehavioral perspective in chronic pain is also necessary for comprehensive management. © The Author(s) 2015.

Effects of similar intakes of marine n-3 fatty acids from enriched food products and fish oil on cardiovascular risk markers in healthy human subjects.

PubMed

Kirkhus, Bente; Lamglait, Amandine; Eilertsen, Karl-Erik; Falch, Eva; Haider, Trond; Vik, Hogne; Hoem, Nils; Hagve, Tor-Arne; Basu, Samar; Olsen, Elisabeth; Seljeflot, Ingebjørg; Nyberg, Lena; Elind, Elisabeth; Ulven, Stine M

2012-05-01

There is convincing evidence that consumption of fish and fish oil rich in long-chain (LC) n-3 PUFA (n-3 LCPUFA), EPA (20 : 5n-3) and DHA (22 : 6n-3) reduce the risk of CHD. The aim of the present study was to investigate whether n-3 LCPUFA-enriched food products provide similar beneficial effects as fish oil with regard to incorporation into plasma lipids and effects on cardiovascular risk markers. A parallel 7-week intervention trial was performed where 159 healthy men and women were randomised to consume either 34 g fish pâté (n 44), 500 ml fruit juice (n 38) or three capsules of concentrated fish oil (n 40), all contributing to a daily intake of approximately 1 g EPA and DHA. A fourth group did not receive any supplementation or food product and served as controls (n 37). Plasma fatty acid composition, serum lipids, and markers of inflammation and oxidative stress were measured. Compared with the control group, plasma n-3 LCPUFA and EPA:arachidonic acid ratio increased equally in all intervention groups. However, no significant changes in blood lipids and markers of inflammation and oxidative stress were observed. In conclusion, enriched fish pâté and fruit juice represent suitable delivery systems for n-3 LCPUFA. However, although the dose given is known to reduce the risk of CVD, no significant changes were observed on cardiovascular risk markers in this healthy population.

Prospective study of hemostatic alterations in children with acute lymphoblastic leukemia.

PubMed

Giordano, Paola; Molinari, Angelo Claudio; Del Vecchio, Giovanni Carlo; Saracco, Paola; Russo, Giovanna; Altomare, Maria; Perutelli, Paolo; Crescenzio, Nicoletta; Santoro, Nicola; Marchetti, Marina; De Mattia, Domenico; Falanga, Anna

2010-05-01

In a group of newly diagnosed acute lymphocytic leukemia (ALL) children we evaluated a number of hemostatic and inflammatory markers at diagnosis and at different time points during chemotherapy for the remission induction to identify alterations in the plasma levels of prothrombotic markers before and during the course of chemotherapy. The following plasma markers were evaluated: thrombin-antithrombin complex (TAT), D-Dimer, plasminogen activator inhibitor 1 (PAI-1), antithrombin, fibrinogen, von Willebrand factor (VWF) antigen and high molecular weight VWF (HMW-VWF) multimers, P-selectin, tumor necrosis factor alpha (TNF-alpha), and interleukin 6 (IL-6). Plasma samples were collected at the following time points: at T0 (baseline) and T1 (+24 days of therapy), T2 (+36 days therapy), and T3 (+64 days therapy). The results show that, at diagnosis, ALL children presented with laboratory signs of increased thrombin generation and fibrin formation (i.e. high TAT and D-dimer levels), fibrinolysis inhibition (i.e. high PAI-1 level), endothelial activation (i.e., high HMW-VWF and soluble P-selectin levels) and inflammation (i.e. high TNF-alpha and IL-6 levels). After starting induction therapy, the thrombin generation markers and inflammatory cytokines significantly decreased. To the opposite, PAI-1 and P-selectin significantly increased, suggesting an insult by chemotherapy on the vascular endothelium. These effects were more evident during steroid administration. Symptomatic venous thromboembolism (VTE) episodes developed in two cases during induction therapy, which did not allow the evaluation of the predictive value for VTE of laboratory markers. (c) 2010 Wiley-Liss, Inc.

ASTROCYTE PATHOLOGY IN MAJOR DEPRESSIVE DISORDER: INSIGHTS FROM HUMAN POSTMORTEM BRAIN TISSUE

PubMed Central

Rajkowska, Grazyna; Stockmeier, Craig A.

2013-01-01

The present paper reviews astrocyte pathology in major depressive disorder (MDD) and proposes that reductions in astrocytes and related markers are key features in the pathology of MDD. Astrocytes are the most numerous and versatile of all types of glial cells. They are crucial to the neuronal microenvironment by regulating glucose metabolism, neurotransmitter uptake (particularly for glutamate), synaptic development and maturation and the blood brain barrier. Pathology of astrocytes has been consistently noted in MDD as well as in rodent models of depressive-like behavior. This review summarizes evidence from human postmortem tissue showing alterations in the expression of protein and mRNA for astrocyte markers such as glial fibrillary acidic protein (GFAP), gap junction proteins (connexin 40 and 43), the water channel aquaporin-4 (AQP4), a calcium-binding protein S100B and glutamatergic markers including the excitatory amino acid transporters 1 and 2 (EAAT1, EAAT2) and glutamine synthetase. Moreover, preclinical studies are presented that demonstrate the involvement of GFAP and astrocytes in animal models of stress and depressive-like behavior and the influence of different classes of antidepressant medications on astrocytes. In light of the various astrocyte deficits noted in MDD, astrocytes may be novel targets for the action of antidepressant medications. Possible functional consequences of altered expression of astrocytic markers in MDD are also discussed. Finally, the unique pattern of cell pathology in MDD, characterized by prominent reductions in the density of astrocytes and in the expression of their markers without obvious neuronal loss, is contrasted with that found in other neuropsychiatric and neurodegenerative disorders. PMID:23469922

Early Prognostication Markers in Cardiac Arrest Patients Treated with Hypothermia

PubMed Central

Karapetkova, Maria; Koenig, Matthew A.; Jia, Xiaofeng

2015-01-01

Background and purpose Established prognostication markers, such as clinical findings, electroencephalography (EEG), and biochemical markers, used by clinicians to predict neurologic outcome after cardiac arrest (CA) are altered under therapeutic hypothermia (TH) conditions and their validity remains uncertain. Methods MEDLINE and EMBASE were searched for evidence on the current standards for neurologic outcome prediction for out-of-hospital CA patients treated with TH and the validity of a wide range of prognostication markers. Relevant studies that suggested one or several established biomarkers, and multimodal approaches for prognostication were included and reviewed. Results While the prognostic accuracy of various tests has been questioned after TH, pupillary light reflexes and somatosensory evoked potentials (SSEP) are still strongly associated with negative outcome for early prognostication. Increasingly, EEG background activity has also been identified as a valid predictor for outcome after 72 hours after CA and a preferred prognostic method in clinical settings. Neuroimaging techniques, such as MRI and CT, can identify functional and structural brain injury, but are not readily available at the patient’s bedside because of limited availability and high costs. Conclusions A multimodal algorithm composed of neurological examination, EEG-based quantitative testing, and SSEP, in conjunction with newer MRI sequences, if available, holds promise for accurate prognostication in CA patients treated with TH. In order to avoid premature withdrawal of care, prognostication should be performed later than 72 hours after CA. PMID:26228521

Early prognostication markers in cardiac arrest patients treated with hypothermia.

PubMed

Karapetkova, M; Koenig, M A; Jia, X

2016-03-01

Established prognostication markers, such as clinical findings, electroencephalography (EEG) and biochemical markers, used by clinicians to predict neurological outcome after cardiac arrest (CA) are altered under therapeutic hypothermia (TH) conditions and their validity remains uncertain. MEDLINE and Embase were searched for evidence on the current standards for neurological outcome prediction for out-of-hospital CA patients treated with TH and the validity of a wide range of prognostication markers. Relevant studies that suggested one or several established biomarkers and multimodal approaches for prognostication are included and reviewed. Whilst the prognostic accuracy of various tests after TH has been questioned, pupillary light reflexes and somatosensory evoked potentials are still strongly associated with negative outcome for early prognostication. Increasingly, EEG background activity has also been identified as a valid predictor for outcome after 72 h after CA and a preferred prognostic method in clinical settings. Neuroimaging techniques, such as magnetic resonance imaging and computed tomography, can identify functional and structural brain injury but are not readily available at the patient's bedside because of limited availability and high costs. A multimodal algorithm composed of neurological examination, EEG-based quantitative testing and somatosensory evoked potentials, in conjunction with newer magnetic resonance imaging sequences, if available, holds promise for accurate prognostication in CA patients treated with TH. In order to avoid premature withdrawal of care, prognostication should be performed more than 72 h after CA. © 2015 EAN.

Multiple point mutations in a shuttle vector propagated in human cells: evidence for an error-prone DNA polymerase activity.

PubMed

Seidman, M M; Bredberg, A; Seetharam, S; Kraemer, K H

1987-07-01

Mutagenesis was studied at the DNA-sequence level in human fibroblast and lymphoid cells by use of a shuttle vector plasmid, pZ189, containing a suppressor tRNA marker gene. In a series of experiments, 62 plasmids were recovered that had two to six base substitutions in the 160-base-pair marker gene. Approximately 20-30% of the mutant plasmids that were recovered after passing ultraviolet-treated pZ189 through a repair-proficient human fibroblast line contained these multiple mutations. In contrast, passage of ultraviolet-treated pZ189 through an excision-repair-deficient (xeroderma pigmentosum) line yielded only 2% multiple base substitution mutants. Introducing a single-strand nick in otherwise unmodified pZ189 adjacent to the marker, followed by passage through the xeroderma pigmentosum cells, resulted in about 66% multiple base substitution mutants. The multiple mutations were found in a 160-base-pair region containing the marker gene but were rarely found in an adjacent 170-base-pair region. Passing ultraviolet-treated or nicked pZ189 through a repair-proficient human B-cell line also yielded multiple base substitution mutations in 20-33% of the mutant plasmids. An explanation for these multiple mutations is that they were generated by an error-prone polymerase while filling gaps. These mutations share many of the properties displayed by mutations in the immunoglobulin hypervariable regions.

Seven diverse human embryonic stem cell-derived chondrogenic clonal embryonic progenitor cell lines display site-specific cell fates.

PubMed

Sternberg, Hal; Kidd, Jennifer; Murai, James T; Jiang, Jianjie; Rinon, Ariel; Erickson, Isaac E; Funk, Walter D; Wang, Qian; Chapman, Karen B; Vangsness, C Thomas; West, Michael D

2013-03-01

The transcriptomes of seven diverse clonal human embryonic progenitor cell lines with chondrogenic potential were compared with that of bone marrow-derived mesenchymal stem cells (MSCs). The cell lines 4D20.8, 7PEND24, 7SMOO32, E15, MEL2, SK11 and SM30 were compared with MSCs using immunohistochemical methods, gene expression microarrays and quantitative real-time PCR. In the undifferentiated progenitor state, each line displayed unique combinations of site-specific markers, including AJAP1, ALDH1A2, BMP5, BARX1, HAND2, HOXB2, LHX1, LHX8, PITX1, TBX15 and ZIC2, but none of the lines expressed the MSC marker CD74. The lines showed diverse responses when differentiated in the presence of combinations of TGF-β3, BMP2, 4, 6 and 7 and GDF5, with the lines 4D20.8, SK11, SM30 and MEL2 showing osteogenic markers in some differentiation conditions. The line 7PEND24 showed evidence of regenerating articular cartilage and, in some conditions, markers of tendon differentiation. The scalability of site-specific clonal human embryonic stem cell-derived embryonic progenitor cell lines may provide novel models for the study of differentiation and methods for preparing purified and identified cells types for use in therapy.

Clinical Significance of Serum Interleukin-31 and Interleukin-33 Levels in Patients of Endometrial Cancer: A Case Control Study

PubMed Central

Zeng, Xi; Zhang, Zhu; Gao, Qian-Qian; Wang, Yan-Yun; Yu, Xiu-Zhang; Zhou, Bin; Xi, Ming-Rong

2016-01-01

Aims. Previous evidence has proved that interleukin-31 (IL-31) and interleukin-33 (IL-33) can be potential markers in some cancers' formulation. We aimed to determine the potential role of IL-31 and IL-33 in prognosis of endometrial cancer patients. Methods. Serum samples were collected from 160 patients with endometrial cancer and 160 healthy controls. The ELISA kits (Raybio® Systems) specific for human IL-31 and human IL-33 were used. Serum levels of tumor markers (CEA, CA-125, and CA19-9) were measured by chemiluminescence immunoassay. A two-side P value < 0.05 was indicated to be significant. Results. Serum levels of IL-31 and IL-33 in patients were significantly elevated compared to those of healthy controls. The interleukin levels were also related to clinical characteristics, including tumor stages, depth of invasion, and existence of node metastases and distant metastases. The sensitivity and specificity of IL-31 and IL-33 were higher than the counterparts of tumor markers, both separately and in combination of IL-31, IL-33, and the clinical markers. Conclusions. This report is the first one mentioning the possible association between serum IL-31 and IL-33 and endometrial cancer. With their sensitivity and specificity, the interleukins may be useful biomarkers for endometrial cancer's prognosis. PMID:27340318

MUC4, a novel immunohistochemical marker identified by gene expression profiling, differentiates pleural sarcomatoid mesothelioma from lung sarcomatoid carcinoma.

PubMed

Amatya, Vishwa Jeet; Kushitani, Kei; Mawas, Amany Sayed; Miyata, Yoshihiro; Okada, Morihito; Kishimoto, Takumi; Inai, Kouki; Takeshima, Yukio

2017-05-01

Sarcomatoid mesothelioma, a histological subtype of malignant pleural mesothelioma, is a very aggressive tumor with a poor prognosis. Histological diagnosis of sarcomatoid mesothelioma largely depends on the histomorphological feature of spindled tumor cells with immunohistochemical reactivity to cytokeratins. Diagnosis also requires clinico-radiological and/or macroscopic evidence of an extrapulmonary location to differentiate it from lung sarcomatoid carcinoma. Although there are promising immunohistochemical antibody panels to differentiate mesothelioma from lung carcinoma, a consensus on the immunohistochemical markers that distinguish sarcomatoid mesothelioma from lung sarcomatoid carcinoma has not been reached and requires further study. We performed whole gene expression analysis of formalin-fixed paraffin-embedded tissue from sarcomatoid mesothelioma and lung sarcomatoid carcinoma and observed significant differences in the expression of MUC4 and other genes between sarcomatoid mesothelioma and lung sarcomatoid carcinoma. Immunohistochemistry demonstrated that MUC4 was expressed in the spindled tumor cells of lung sarcomatoid carcinoma (21/29, 72%) but was not expressed in any sarcomatoid mesothelioma (0/31, 0%). To differentiate sarcomatoid mesothelioma from lung sarcomatoid carcinoma, negative MUC4 expression showed 100% sensitivity and 72% specificity and accuracy rate of 87%, which is higher than immunohistochemical markers such as calretinin, D2-40 and Claudin-4. Therefore, we recommend to include MUC4 as a novel and useful negative immunohistochemical marker for differentiating sarcomatoid mesothelioma from lung sarcomatoid carcinoma.

First evidence of hybridization between golden jackal (Canis aureus) and domestic dog (Canis familiaris) as revealed by genetic markers

PubMed Central

Fabbri, Elena; Caniglia, Romolo; Arbanasić, Haidi; Lapalombella, Silvana; Florijančić, Tihomir; Bošković, Ivica; Galaverni, Marco

2015-01-01

Interspecific hybridization is relatively frequent in nature and numerous cases of hybridization between wild canids and domestic dogs have been recorded. However, hybrids between golden jackals (Canis aureus) and other canids have not been described before. In this study, we combined the use of biparental (15 autosomal microsatellites and three major histocompatibility complex (MHC) loci) and uniparental (mtDNA control region and a Y-linked Zfy intron) genetic markers to assess the admixed origin of three wild-living canids showing anomalous phenotypic traits. Results indicated that these canids were hybrids between golden jackals and domestic dogs. One of them was a backcross to jackal and another one was a backcross to dog, confirming that golden jackal–domestic dog hybrids are fertile. The uniparental markers showed that the direction of hybridization, namely females of the wild species hybridizing with male domestic dogs, was common to most cases of canid hybridization. A melanistic 3bp-deletion at the K locus (β-defensin CDB103 gene), that was absent in reference golden jackal samples, but was found in a backcross to jackal with anomalous black coat, suggested its introgression from dogs via hybridization. Moreover, we demonstrated that MHC sequences, although rarely used as markers of hybridization, can be also suitable for the identification of hybrids, as long as haplotypes are exclusive for the parental species. PMID:27019731

Genetic examination of the putative skull of Jan Kochanowski reveals its female sex

PubMed Central

Kupiec, Tomasz; Branicki, Wojciech

2011-01-01

We report the results of genetic examination of the putative skull of Jan Kochanowski (1530-1584), a great Polish renaissance poet. The skull was retrieved in 1791 by historian Tadeusz Czacki from the Kochanowski family tomb and became the property of the Czartoryskis Museum in Krakow. An anthropological study in 1926 questioned its male origin, which raised doubts about its authenticity. Our report presents genetic evidence that resolves this dispute. From the sole tooth we obtained a sufficient amount of DNA to perform the analysis of nuclear markers. The analysis of the sex-informative part of intron 1 in amelogenin, genotyped using AmpFiSTR® NGM PCR Amplification Kit and Powerplex® ESI17 Kit human identification systems, revealed the female origin of the tooth. The female origin was further confirmed by the analysis of a portion of amelogenin intron 2, a microsatellite marker located on the X chromosome, as well as by a lack of signal from Y chromosomal microsatellite markers and the sex-determining region Y marker. Data obtained for two hypervariable regions, HVI and HVII, in mitochondrial DNA showed that mtDNA haplotype was relatively frequent among contemporary Europeans. The analysis of a set of single nucleotide polymorphisms relevant for prediction of the iris color indicated an 87% probability that the woman had hazel or brown eye color. PMID:21674838

Genetic examination of the putative skull of Jan Kochanowski reveals its female sex.

PubMed

Kupiec, Tomasz; Branicki, Wojciech

2011-06-01

We report the results of genetic examination of the putative skull of Jan Kochanowski (1530-1584), a great Polish renaissance poet. The skull was retrieved in 1791 by historian Tadeusz Czacki from the Kochanowski family tomb and became the property of the Czartoryskis Museum in Krakow. An anthropological study in 1926 questioned its male origin, which raised doubts about its authenticity. Our report presents genetic evidence that resolves this dispute. From the sole tooth we obtained a sufficient amount of DNA to perform the analysis of nuclear markers. The analysis of the sex-informative part of intron 1 in amelogenin, genotyped using AmpFiSTR® NGM PCR Amplification Kit and Powerplex® ESI17 Kit human identification systems, revealed the female origin of the tooth. The female origin was further confirmed by the analysis of a portion of amelogenin intron 2, a microsatellite marker located on the X chromosome, as well as by a lack of signal from Y chromosomal microsatellite markers and the sex-determining region Y marker. Data obtained for two hypervariable regions, HVI and HVII, in mitochondrial DNA showed that mtDNA haplotype was relatively frequent among contemporary Europeans. The analysis of a set of single nucleotide polymorphisms relevant for prediction of the iris color indicated an 87% probability that the woman had hazel or brown eye color.

Markers of iron deficiency in patients with polycythemia vera receiving ruxolitinib or best available therapy.

PubMed

Verstovsek, Srdan; Harrison, Claire N; Kiladjian, Jean-Jacques; Miller, Carole; Naim, Ahmad B; Paranagama, Dilan C; Habr, Dany; Vannucchi, Alessandro M

2017-05-01

Polycythemia vera (PV) is characterized by erythropoiesis and JAK2-activating mutations, with increased risks of morbidity and mortality. Most patients with PV are iron deficient, and treatment often includes hematocrit control with phlebotomy, which may exacerbate iron deficiency-associated complications. The phase 3 RESPONSE trial evaluated the JAK1/JAK2 inhibitor ruxolitinib (n=110) versus best available therapy (BAT; n=112) in patients with PV who were hydroxyurea-resistant/intolerant. Ruxolitinib was superior to BAT for hematocrit control, reduction in splenomegaly, and blood count normalization. This exploratory analysis, the first to evaluate iron status in a prospective study of patients with PV, investigated ruxolitinib effects on 7 serum iron markers and iron deficiency-related patient-reported outcomes (PRO). Among patients with evidence of baseline iron deficiency, ruxolitinib was associated with normalization of iron marker levels, compared with lesser improvement with BAT. Iron levels remained stable in ruxolitinib patients with normal iron levels at baseline. Regardless of baseline iron status, treatment with ruxolitinib was associated with improvements in concentration problems, cognitive function, dizziness, fatigue, headaches, and inactivity, although improvements were generally greater among patients with baseline iron deficiency. The improvements in iron deficiency markers and PROs observed with ruxolitinib are suggestive of clinical benefits that warrant further exploration. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

AFLPs reveal different population genetic structure under contrasting environments in the marine snail Nucella lapillus L.

PubMed

Carro, Belén; Quintela, María; Ruiz, José Miguel; Barreiro, Rodolfo

2012-01-01

Dispersal has received growing attention in marine ecology, particularly since evidence obtained with up-to-date techniques challenged the traditional view. The dogwhelk Nucella lapillus L., a sedentary gastropod with direct development, is a good example: dispersal was traditionally assumed to be limited until studies with microsatellites disputed this idea. To shed some light on this controversy, the genetic structure of dogwhelk populations in northwest Spain was investigated with highly polymorphic AFLP markers giving special attention to the influence of hydrodynamic stress. In agreement with the expectations for a poor disperser, our results show a significant genetic structure at regional (<200 km) and areal scales (<15 km). However, the spatial genetic structure varied with wave-exposure in the present case study: IBD was evident under sheltered conditions but absent from the exposed area where genetic differentiation was stronger. Our results provide evidence that differences in wave-exposure can exert a detectable influence on the genetic structure of coastal organisms, even in species without a planktonic larva.

Face identity recognition in autism spectrum disorders: a review of behavioral studies.

PubMed

Weigelt, Sarah; Koldewyn, Kami; Kanwisher, Nancy

2012-03-01

Face recognition--the ability to recognize a person from their facial appearance--is essential for normal social interaction. Face recognition deficits have been implicated in the most common disorder of social interaction: autism. Here we ask: is face identity recognition in fact impaired in people with autism? Reviewing behavioral studies we find no strong evidence for a qualitative difference in how facial identity is processed between those with and without autism: markers of typical face identity recognition, such as the face inversion effect, seem to be present in people with autism. However, quantitatively--i.e., how well facial identity is remembered or discriminated--people with autism perform worse than typical individuals. This impairment is particularly clear in face memory and in face perception tasks in which a delay intervenes between sample and test, and less so in tasks with no memory demand. Although some evidence suggests that this deficit may be specific to faces, further evidence on this question is necessary. Copyright © 2011 Elsevier Ltd. All rights reserved.

Current concepts regarding calcium metabolism and bone health in sarcoidosis.

PubMed

Baughman, Robert P; Papanikolaou, Ilias

2017-09-01

Vitamin D supplementation is widespread used in the general population. In sarcoidosis, up to 50% of patients, especially postmenopausal women and those taking corticosteroids, show evidence of increased bone fragility. The purpose of this review is to provide an evidence-based rationale on how to treat sarcoidosis patients with bone health issues. Evidence from observational studies show that decreased 25-hydroxy vitamin D is common in sarcoidosis. However, the great majority of sarcoidosis patents have normal or often elevated levels of 1,25-dihydroxy vitamin D (calcitriol), a marker associated with disease activity. High calcitriol levels may often be associated with hypercalcemia and hypercalcuria. The few interventional randomized controlled studies in the field, suggest that vitamin D supplementation may not be well tolerated because of hypercalcemia, moreover without substantial benefit on bone health and risk for fractures in these patients. Vitamin D supplementation may be withheld in sarcoidosis patients with bone fragility, unless calcitriol levels are below normal limits. A treating scheme is proposed.

A Genome-Wide Survey of Genetic Instability by Transposition in Drosophila Hybrids

PubMed Central

Vela, Doris; Fontdevila, Antonio; Vieira, Cristina; García Guerreiro, María Pilar

2014-01-01

Hybridization between species is a genomic instability factor involved in increasing mutation rate and new chromosomal rearrangements. Evidence of a relationship between interspecific hybridization and transposable element mobilization has been reported in different organisms, but most studies are usually performed with particular TEs and do not discuss the real effect of hybridization on the whole genome. We have therefore studied whole genome instability of Drosophila interspecific hybrids, looking for the presence of new AFLP markers in hybrids. A high percentage (27–90%) of the instability markers detected corresponds to TEs belonging to classes I and II. Moreover, three transposable elements (Osvaldo, Helena and Galileo) representative of different families, showed an overall increase of transposition rate in hybrids compared to parental species. This research confirms the hypothesis that hybridization induces genomic instability by transposition bursts and suggests that genomic stress by transposition could contribute to a relaxation of mechanisms controlling TEs in the Drosophila genome. PMID:24586475

Uncoupling of sexual reproduction from homologous recombination in homozygous Oenothera species.

PubMed

Rauwolf, U; Greiner, S; Mráček, J; Rauwolf, M; Golczyk, H; Mohler, V; Herrmann, R G; Meurer, J

2011-07-01

Salient features of the first meiotic division are independent segregation of chromosomes and homologous recombination (HR). In non-sexually reproducing, homozygous species studied to date HR is absent. In this study, we constructed the first linkage maps of homozygous, bivalent-forming Oenothera species and provide evidence that HR was exclusively confined to the chromosome ends of all linkage groups in our population. Co-segregation of complementary DNA-based markers with the major group of AFLP markers indicates that HR has only a minor role in generating genetic diversity of this taxon despite its efficient adaptation capability. Uneven chromosome condensation during meiosis in Oenothera may account for restriction of HR. The use of plants with ancient chromosomal arm arrangement demonstrates that limitation of HR occurred before and independent from species hybridizations and reciprocal translocations of chromosome arms-a phenomenon, which is widespread in the genus. We propose that consecutive loss of HR favored the evolution of reciprocal translocations, beneficial superlinkage groups and ultimately permanent translocation heterozygosity.

Linguistic labels, dynamic visual features, and attention in infant category learning.

PubMed

Deng, Wei Sophia; Sloutsky, Vladimir M

2015-06-01

How do words affect categorization? According to some accounts, even early in development words are category markers and are different from other features. According to other accounts, early in development words are part of the input and are akin to other features. The current study addressed this issue by examining the role of words and dynamic visual features in category learning in 8- to 12-month-old infants. Infants were familiarized with exemplars from one category in a label-defined or motion-defined condition and then tested with prototypes from the studied category and from a novel contrast category. Eye-tracking results indicated that infants exhibited better category learning in the motion-defined condition than in the label-defined condition, and their attention was more distributed among different features when there was a dynamic visual feature compared with the label-defined condition. These results provide little evidence for the idea that linguistic labels are category markers that facilitate category learning. Copyright © 2015 Elsevier Inc. All rights reserved.

Linguistic Labels, Dynamic Visual Features, and Attention in Infant Category Learning

PubMed Central

Deng, Wei (Sophia); Sloutsky, Vladimir M.

2015-01-01

How do words affect categorization? According to some accounts, even early in development, words are category markers and are different from other features. According to other accounts, early in development, words are part of the input and are akin to other features. The current study addressed this issue by examining the role of words and dynamic visual features in category learning in 8- to 12- month infants. Infants were familiarized with exemplars from one category in a label-defined or motion-defined condition and then tested with prototypes from the studied category and from a novel contrast category. Eye tracking results indicated that infants exhibited better category learning in the motion-defined than in the label-defined condition and their attention was more distributed among different features when there was a dynamic visual feature compared to the label-defined condition. These results provide little evidence for the idea that linguistic labels are category markers that facilitate category learning. PMID:25819100