X-linked recessive panhypopituitarism associated with a regional duplication in Xq25-q26.

PubMed Central

Lagerström-Fermér, M; Sundvall, M; Johnsen, E; Warne, G L; Forrest, S M; Zajac, J D; Rickards, A; Ravine, D; Landegren, U; Pettersson, U

1997-01-01

We present a linkage analysis and a clinical update on a previously reported family with X-linked recessive panhypopituitarism, now in its fourth generation. Affected members exhibit variable degrees of hypopituitarism and mental retardation. The markers DXS737 and DXS1187 in the q25-q26 region of the X chromosome showed evidence for linkage with a peak LOD score (Zmax) of 4.12 at zero recombination fraction (theta(max) = 0). An apparent extra copy of the marker DXS102, observed in the region of the disease gene in affected males and heterozygous carrier females, suggests that a segment including this marker is duplicated. The gene causing this disorder appears to code for a dosage-sensitive protein central to development of the pituitary. Images Figure 2 PMID:9106538

High FIB-4 index as an independent risk factor of prevalent chronic kidney disease in patients with nonalcoholic fatty liver disease.

PubMed

Xu, Huang-Wei; Hsu, Yung-Chien; Chang, Chia-Hao; Wei, Kuo-Liang; Lin, Chun-Liang

2016-03-01

Growing evidence suggests that non-alcoholic fatty liver disease (NAFLD) is linked to an increased risk for chronic kidney disease (CKD); liver fibrosis with biopsy-proven NAFLD has also been shown to associate with an increased risk of CKD. This study compares the diagnostic performance of simple noninvasive tests in identifying prevalent CKD among individuals with ultrasonography-diagnosed NAFLD. A total of 755 with ultrasonography-diagnosed NAFLD were included. Estimated glomerular filtration rate and noninvasive markers for hepatic fibrosis: aspartate transaminase to alanine transaminase ratio (AAR), aspartate transaminase to platelet ratio index (APRI), FIB-4 score, NAFLD fibrosis score (NFS) and BARD score were assessed. Binary logistic regression to generate a propensity score and receiver operating characteristic curves were developed for each of the noninvasive markers for predicting CKD, and the area under the receiver operating characteristic curve was greatest for FIB-4 score (0.750), followed by NFS (0.710), AAR (0.594), APRI (0.587), and BARD score (0.561). A cut-off value of 1.100 for FIB-4 score gave a sensitivity of 68.85% and a specificity of 71.07% for predicting CKD. The positive predictive value and negative predictive value were 37.50 and 90.05%, respectively. In multiple logistic regression analysis, only FIB-4 score ≧1.100 (OR 2.660, 95% CI 1.201-5.889; p = .016), older age, higher diastolic blood pressure and higher uric acid were independent predictors of CKD. High noninvasive fibrosis score is associated with an increased risk of prevalent CKD; the FIB-4 is the better predictor. With a cut-off value of 1.100 for FIB-4, it is useful in excluding the presence of CKD in patients with NAFLD.

Performance of automated scoring of ER, PR, HER2, CK5/6 and EGFR in breast cancer tissue microarrays in the Breast Cancer Association Consortium

PubMed Central

Howat, William J; Blows, Fiona M; Provenzano, Elena; Brook, Mark N; Morris, Lorna; Gazinska, Patrycja; Johnson, Nicola; McDuffus, Leigh‐Anne; Miller, Jodi; Sawyer, Elinor J; Pinder, Sarah; van Deurzen, Carolien H M; Jones, Louise; Sironen, Reijo; Visscher, Daniel; Caldas, Carlos; Daley, Frances; Coulson, Penny; Broeks, Annegien; Sanders, Joyce; Wesseling, Jelle; Nevanlinna, Heli; Fagerholm, Rainer; Blomqvist, Carl; Heikkilä, Päivi; Ali, H Raza; Dawson, Sarah‐Jane; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli‐Matti; Cox, Angela; Brock, Ian W; Cross, Simon S; Reed, Malcolm W; Couch, Fergus J; Olson, Janet E; Devillee, Peter; Mesker, Wilma E; Seyaneve, Caroline M; Hollestelle, Antoinette; Benitez, Javier; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Bolla, Manjeet K; Easton, Douglas F; Schmidt, Marjanka K; Pharoah, Paul D; Sherman, Mark E

2014-01-01

Abstract Breast cancer risk factors and clinical outcomes vary by tumour marker expression. However, individual studies often lack the power required to assess these relationships, and large‐scale analyses are limited by the need for high throughput, standardized scoring methods. To address these limitations, we assessed whether automated image analysis of immunohistochemically stained tissue microarrays can permit rapid, standardized scoring of tumour markers from multiple studies. Tissue microarray sections prepared in nine studies containing 20 263 cores from 8267 breast cancers stained for two nuclear (oestrogen receptor, progesterone receptor), two membranous (human epidermal growth factor receptor 2 and epidermal growth factor receptor) and one cytoplasmic (cytokeratin 5/6) marker were scanned as digital images. Automated algorithms were used to score markers in tumour cells using the Ariol system. We compared automated scores against visual reads, and their associations with breast cancer survival. Approximately 65–70% of tissue microarray cores were satisfactory for scoring. Among satisfactory cores, agreement between dichotomous automated and visual scores was highest for oestrogen receptor (Kappa = 0.76), followed by human epidermal growth factor receptor 2 (Kappa = 0.69) and progesterone receptor (Kappa = 0.67). Automated quantitative scores for these markers were associated with hazard ratios for breast cancer mortality in a dose‐response manner. Considering visual scores of epidermal growth factor receptor or cytokeratin 5/6 as the reference, automated scoring achieved excellent negative predictive value (96–98%), but yielded many false positives (positive predictive value = 30–32%). For all markers, we observed substantial heterogeneity in automated scoring performance across tissue microarrays. Automated analysis is a potentially useful tool for large‐scale, quantitative scoring of immunohistochemically stained tissue microarrays available in consortia. However, continued optimization, rigorous marker‐specific quality control measures and standardization of tissue microarray designs, staining and scoring protocols is needed to enhance results. PMID:27499890

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

Assignment of the Nance-Horan syndrome to the distal short arm of the X chromosome.

PubMed

Zhu, D; Alcorn, D M; Antonarakis, S E; Levin, L S; Huang, P C; Mitchell, T N; Warren, A C; Maumenee, I H

1990-11-01

There are three types of X-linked cataracts recorded in Mendelian Inheritance in Man (McKusick 1988): congenital total, with posterior sutural opacities in heterozygotes; congenital, with microcornea or slight microphthalmia; and the cataract-dental syndrome or Nance-Horan (NH) syndrome. To identify a DNA marker close to the gene responsible for the NH syndrome, linkage analysis on 36 members in a three-generation pedigree including seven affected males and nine carrier females was performed using 31 DNA markers. A LOD score of 1.662 at theta = 0.16 was obtained with probe 782 from locus DXS85 on Xp22.2-p22.3. Negative LOD scores were found at six loci on the short arm, one distal to DXS85, five proximal, and six probes spanning the long arm were highly negative. These results make the assignment of the locus for NH to the distal end of the short arm of the X chromosome likely.

Preoperative liver dysfunction influences blood product administration and alterations in circulating haemostatic markers following ventricular assist device implantation.

PubMed

Woolley, Joshua R; Kormos, Robert L; Teuteberg, Jeffrey J; Bermudez, Christian A; Bhama, Jay K; Lockard, Kathleen L; Kunz, Nicole M; Wagner, William R

2015-03-01

Preoperative liver dysfunction may influence haemostasis following ventricular assist device (VAD) implantation. The Model for End-stage Liver Disease (MELD) score was assessed as a predictor of bleeding and levels of haemostatic markers in patients with currently utilized VADs. Sixty-three patients (31 HeartMate II, 15 HeartWare, 17 Thoratec paracorporeal ventricular assist device) implanted 2001-11 were analysed for preoperative liver dysfunction (MELD) and blood product administration. Of these patients, 21 had additional blood drawn to measure haemostatic marker levels. Cohorts were defined based on high (≥18.0, n = 7) and low (<18.0, n = 14) preoperative MELD scores. MELD score was positively correlated with postoperative administration of red blood cell (RBC), platelet, plasma and total blood product units (TBPU) , as well as chest tube drainage and cardiopulmonary bypass time. Age and MELD were preoperative predictors of TBPU by multivariate analysis. The high-MELD cohort had higher administration of TBPU, RBC and platelet units and chest tube drainage postimplant. Similarly, patients who experienced at least one bleeding adverse event were more likely to have had a high preoperative MELD. The high-MELD group exhibited different temporal trends in F1 + 2 levels and platelet counts to postoperative day (POD) 55. D-dimer levels in high-MELD patients became elevated versus those for low-MELD patients on POD 55. Preoperative MELD score predicts postoperative bleeding in contemporary VADs. Preoperative liver dysfunction may also alter postoperative subclinical haemostasis through different temporal trends of thrombin generation and platelet counts, as well as protracted fibrinolysis. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Improving lung cancer prognosis assessment by incorporating synthetic minority oversampling technique and score fusion method

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

Yan, Shiju; Qian, Wei; Guan, Yubao

2016-06-15

Purpose: This study aims to investigate the potential to improve lung cancer recurrence risk prediction performance for stage I NSCLS patients by integrating oversampling, feature selection, and score fusion techniques and develop an optimal prediction model. Methods: A dataset involving 94 early stage lung cancer patients was retrospectively assembled, which includes CT images, nine clinical and biological (CB) markers, and outcome of 3-yr disease-free survival (DFS) after surgery. Among the 94 patients, 74 remained DFS and 20 had cancer recurrence. Applying a computer-aided detection scheme, tumors were segmented from the CT images and 35 quantitative image (QI) features were initiallymore » computed. Two normalized Gaussian radial basis function network (RBFN) based classifiers were built based on QI features and CB markers separately. To improve prediction performance, the authors applied a synthetic minority oversampling technique (SMOTE) and a BestFirst based feature selection method to optimize the classifiers and also tested fusion methods to combine QI and CB based prediction results. Results: Using a leave-one-case-out cross-validation (K-fold cross-validation) method, the computed areas under a receiver operating characteristic curve (AUCs) were 0.716 ± 0.071 and 0.642 ± 0.061, when using the QI and CB based classifiers, respectively. By fusion of the scores generated by the two classifiers, AUC significantly increased to 0.859 ± 0.052 (p < 0.05) with an overall prediction accuracy of 89.4%. Conclusions: This study demonstrated the feasibility of improving prediction performance by integrating SMOTE, feature selection, and score fusion techniques. Combining QI features and CB markers and performing SMOTE prior to feature selection in classifier training enabled RBFN based classifier to yield improved prediction accuracy.« less

Conclusion of LOD-score analysis for family data generated under two-locus models.

PubMed

Dizier, M H; Babron, M C; Clerget-Darpoux, F

1996-06-01

The power to detect linkage by the LOD-score method is investigated here for diseases that depend on the effects of two genes. The classical strategy is, first, to detect a major-gene (MG) effect by segregation analysis and, second, to seek for linkage with genetic markers by the LOD-score method using the MG parameters. We already showed that segregation analysis can lead to evidence for a MG effect for many two-locus models, with the estimates of the MG parameters being very different from those of the two genes involved in the disease. We show here that use of these MG parameter estimates in the LOD-score analysis may lead to a failure to detect linkage for some two-locus models. For these models, use of the sib-pair method gives a non-negligible increase of power to detect linkage. The linkage-homogeneity test among subsamples differing for the familial disease distribution provides evidence of parameter misspecification, when the MG parameters are used. Moreover, for most of the models, use of the MG parameters in LOD-score analysis leads to a large bias in estimation of the recombination fraction and sometimes also to a rejection of linkage for the true recombination fraction. A final important point is that a strong evidence of an MG effect, obtained by segregation analysis, does not necessarily imply that linkage will be detected for at least one of the two genes, even with the true parameters and with a close informative marker.

Only White Matter Hyperintensities Predicts Post-Stroke Cognitive Performances Among Cerebral Small Vessel Disease Markers: Results from the TABASCO Study.

PubMed

Molad, Jeremy; Kliper, Efrat; Korczyn, Amos D; Ben Assayag, Einor; Ben Bashat, Dafna; Shenhar-Tsarfaty, Shani; Aizenstein, Orna; Shopin, Ludmila; Bornstein, Natan M; Auriel, Eitan

2017-01-01

White matter hyperintensities (WMH) were shown to predict cognitive decline following stroke or transient ischemic attack (TIA). However, WMH are only one among other radiological markers of cerebral small vessel disease (SVD). The aim of this study was to determine whether adding other SVD markers to WMH improves prediction of post-stroke cognitive performances. Consecutive first-ever stroke or TIA patients (n = 266) from the Tel Aviv Acute Brain Stroke Cohort (TABASCO) study were enrolled. MRI scans were performed within seven days of stroke onset. We evaluated the relationship between cognitive performances one year following stroke, and previously suggested total SVD burden score including WMH, lacunes, cerebral microbleeds (CMB), and perivascular spaces (PVS). Significant negative associations were found between WMH and cognition (p < 0.05). Adding other SVD markers (lacunes, CMB, PVS) to WMH did not improve predication of post-stroke cognitive performances. Negative correlations between SVD burden score and cognitive scores were observed for global cognitive, memory, and visual spatial scores (all p < 0.05). However, following an adjustment for confounders, no associations remained significant. WMH score was associated with poor post-stroke cognitive performance. Adding other SVD markers or SVD burden score, however, did not improve prediction.

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

Kim, D.; Worster, T.; Boustany, R.M.

The neuronal lipofuscinoses (NCLs) are a group of disorders characterized by cognitive decline, blindness, seizures, and death. Pathologically, it is characterized by accumulation of lipofuscin deposits, generally in easily identifiable `curvilinear bodies`. It is inherited as an autosomal recessive disorder, with the exception of the adult onset form, which may be inherited as an autosomal dominant trait. The loci for the juvenile (CLN3), infantile (CLN1), and very recently, Finnish late-infantile (CLN5) NCLs have been mapped by genetic linkage analysis to chromosome 16p, 1p, and 13q, respectively. The classical late-infantile (LNCL) defect (CLN2) has not yet been mapped. Previous analysis withmore » tightly linked markers excluded CLN2 from the CLN1 and CLN3 regions. We have initiated a genome-wide screen for CLN2, taking advantage of the large collection of highly polymorphic markers that has been developed through the Human Genome Initiative. The high degree of heterozygosity of these markers makes it feasible to carry out successful linkage analysis in small nuclear families, such as found in LNCL. Our current collection of LNCL pedigrees includes 19 U.S. families and 11 Costa Rican families. Simulation studies have shown that we can detect linkage using a subset of 6 LNCL families, a 10 cM sieve, and a lod score criterion of 0.50 for follow-up. A linked region spanned by two markers has over a 95% chance of generating such a lod score, while an unlinked marker has less than a 5% chance of doing so. Follow-up will consist of genotyping the additional families and two additional markers in this region. To date, we have completed typing with 65 markers on chromosomes 1, 2, 9, 13, 16, 18, 19, 20, 21, and 22. The results of this analysis formally exclude about 25% of the human genome as the location of CLN2, including the region of chromosome 13 where CLN5 has been mapped. Updated results will be presented.« less

Empirical Selection of Informative Microsatellite Markers within Co-ancestry Pig Populations Is Required for Improving the Individual Assignment Efficiency

PubMed Central

Li, Y. H.; Chu, H. P.; Jiang, Y. N.; Lin, C. Y.; Li, S. H.; Li, K. T.; Weng, G. J.; Cheng, C. C.; Lu, D. J.; Ju, Y. T.

2014-01-01

The Lanyu is a miniature pig breed indigenous to Lanyu Island, Taiwan. It is distantly related to Asian and European pig breeds. It has been inbred to generate two breeds and crossed with Landrace and Duroc to produce two hybrids for laboratory use. Selecting sets of informative genetic markers to track the genetic qualities of laboratory animals and stud stock is an important function of genetic databases. For more than two decades, Lanyu derived breeds of common ancestry and crossbreeds have been used to examine the effectiveness of genetic marker selection and optimal approaches for individual assignment. In this paper, these pigs and the following breeds: Berkshire, Duroc, Landrace and Yorkshire, Meishan and Taoyuan, TLRI Black Pig No. 1, and Kaohsiung Animal Propagation Station Black pig are studied to build a genetic reference database. Nineteen microsatellite markers (loci) provide information on genetic variation and differentiation among studied breeds. High differentiation index (FST) and Cavalli-Sforza chord distances give genetic differentiation among breeds, including Lanyu’s inbred populations. Inbreeding values (FIS) show that Lanyu and its derived inbred breeds have significant loss of heterozygosity. Individual assignment testing of 352 animals was done with different numbers of microsatellite markers in this study. The testing assigned 99% of the animals successfully into their correct reference populations based on 9 to 14 markers ranking D-scores, allelic number, expected heterozygosity (HE) or FST, respectively. All miss-assigned individuals came from close lineage Lanyu breeds. To improve individual assignment among close lineage breeds, microsatellite markers selected from Lanyu populations with high polymorphic, heterozygosity, FST and D-scores were used. Only 6 to 8 markers ranking HE, FST or allelic number were required to obtain 99% assignment accuracy. This result suggests empirical examination of assignment-error rates is required if discernible levels of co-ancestry exist. In the reference group, optimum assignment accuracy was achievable achieved through a combination of different markers by ranking the heterozygosity, FST and allelic number of close lineage populations. PMID:25049996

Transferability of STS markers in studying genetic relationships of marvel grass (Dichanthium annulatum).

PubMed

Saxena, Raghvendra; Chandra, Amaresh

2011-11-01

Transferability of sequence-tagged-sites (STS) markers was assessed for genetic relationships study among accessions of marvel grass (Dichanthium annulatum Forsk.). In total, 17 STS primers of Stylosanthes origin were tested for their reactivity with thirty accessions of Dichanthium annulatum. Of these, 14 (82.4%) reacted and a total 106 (84 polymorphic) bands were scored. The number of bands generated by individual primer pairs ranged from 4 to 11 with an average of 7.57 bands, whereas polymorphic bands ranged from 4 to 9 with an average of 6.0 bands accounts to an average polymorphism of 80.1%. Polymorphic information content (PIC) ranged from 0.222 to 0.499 and marker index (MI) from 1.33 to 4.49. Utilizing Dice coefficient of genetic similarity dendrogram was generated through un-weighted pairgroup method with arithmetic mean (UPGMA) algorithm. Further, clustering through sequential agglomerative hierarchical and nested (SAHN) method resulted three main clusters constituted all accessions except IGBANG-D-2. Though there was intermixing of few accessions of one agro-climatic region to another, largely groupings of accessions were with their regions of collections. Bootstrap analysis at 1000 scale also showed large number of nodes (11 to 17) having strong clustering (> 50). Thus, results demonstrate the utility of STS markers of Stylosanthes in studying the genetic relationships among accessions of Dichanthium.

Linkage analysis of candidate genes in autoimmune thyroid disease. II. Selected gender-related genes and the X-chromosome. International Consortium for the Genetics of Autoimmune Thyroid Disease.

PubMed

Barbesino, G; Tomer, Y; Concepcion, E S; Davies, T F; Greenberg, D A

1998-09-01

Hashimoto's thyroiditis (HT) and Graves' disease (GD) are autoimmune thyroid diseases (AITD) in which multiple genetic factors are suspected to play an important role. Until now, only a few minor risk factors for these diseases have been identified. Susceptibility seems to be stronger in women, pointing toward a possible role for genes related to sex steroid action or mechanisms related to genes on the X-chromosome. We have studied a total of 45 multiplex families, each containing at least 2 members affected with either GD (55 patients) or HT (72 patients), and used linkage analysis to target as candidate susceptibility loci genes involved in estrogen activity, such as the estrogen receptor alpha and beta and the aromatase genes. We then screened the entire X-chromosome using a set of polymorphic microsatellite markers spanning the whole chromosome. We found a region of the X-chromosome (Xq21.33-22) giving positive logarithm of odds (LOD) scores and then reanalyzed this area with dense markers in a multipoint analysis. Our results excluded linkage to the estrogen receptor alpha and aromatase genes when either the patients with GD only, those with HT only, or those with any AITD were considered as affected. Linkage to the estrogen receptor beta could not be totally ruled out, partly due to incomplete mapping information for the gene itself at this time. The X-chromosome data revealed consistently positive LOD scores (maximum of 1.88 for marker DXS8020 and GD patients) when either definition of affectedness was considered. Analysis of the family data using a multipoint analysis with eight closely linked markers generated LOD scores suggestive of linkage to GD in a chromosomal area (Xq21.33-22) extending for about 6 cM and encompassing four markers. The maximum LOD score (2.5) occurred at DXS8020. In conclusion, we ruled out a major role for estrogen receptor alpha and the aromatase genes in the genetic predisposition to AITD. Estrogen receptor beta remains a candidate locus. We found a locus on Xq21.33-22 linked to GD that may help to explain the female predisposition to GD. Confirmation of these data in HT may require study of an extended number of families because of possible heterogeneity.

Molecular diversity analysis of Tetradium ruticarpum (WuZhuYu) in China based on inter-primer binding site (iPBS) markers and inter-simple sequence repeat (ISSR) markers.

PubMed

Xu, Jing-Yuan; Zhu, Yan; Yi, Ze; Wu, Gang; Xie, Guo-Yong; Qin, Min-Jian

2018-01-01

"Wu zhu yu", which is obtained from the dried unripe fruits of Tetradium ruticarpum (A. Jussieu) T. G. Hartley, has been used as a traditional Chinese medicine for treatment of headaches, abdominal colic, and hypertension for thousands of years. The present study was designed to assess the molecular genetic diversity among 25 collected accessions of T. ruticarpum (Wu zhu yu in Chinese) from different areas of China, based on inter-primer binding site (iPBS) markers and inter-simple sequence repeat (ISSR) markers. Thirteen ISSR primers generated 151 amplification bands, of which 130 were polymorphic. Out of 165 bands that were amplified using 10 iPBS primers, 152 were polymorphic. The iPBS markers displayed a higher proportion of polymorphic loci (PPL = 92.5%) than the ISSR markers (PPL = 84.9%). The results showed that T. ruticarpum possessed high loci polymorphism and genetic differentiation occurred in this plant. The combined data of iPBS and ISSR markers scored on 25 accessions produced five clusters that approximately matched the geographic distribution of the species. The results indicated that both iPBS and ISSR markers were reliable and effective tools for analyzing the genetic diversity in T. ruticarpum. Copyright © 2018 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Mining the human phenome using allelic scores that index biological intermediates.

PubMed

Evans, David M; Brion, Marie Jo A; Paternoster, Lavinia; Kemp, John P; McMahon, George; Munafò, Marcus; Whitfield, John B; Medland, Sarah E; Montgomery, Grant W; Timpson, Nicholas J; St Pourcain, Beate; Lawlor, Debbie A; Martin, Nicholas G; Dehghan, Abbas; Hirschhorn, Joel; Smith, George Davey

2013-10-01

It is common practice in genome-wide association studies (GWAS) to focus on the relationship between disease risk and genetic variants one marker at a time. When relevant genes are identified it is often possible to implicate biological intermediates and pathways likely to be involved in disease aetiology. However, single genetic variants typically explain small amounts of disease risk. Our idea is to construct allelic scores that explain greater proportions of the variance in biological intermediates, and subsequently use these scores to data mine GWAS. To investigate the approach's properties, we indexed three biological intermediates where the results of large GWAS meta-analyses were available: body mass index, C-reactive protein and low density lipoprotein levels. We generated allelic scores in the Avon Longitudinal Study of Parents and Children, and in publicly available data from the first Wellcome Trust Case Control Consortium. We compared the explanatory ability of allelic scores in terms of their capacity to proxy for the intermediate of interest, and the extent to which they associated with disease. We found that allelic scores derived from known variants and allelic scores derived from hundreds of thousands of genetic markers explained significant portions of the variance in biological intermediates of interest, and many of these scores showed expected correlations with disease. Genome-wide allelic scores however tended to lack specificity suggesting that they should be used with caution and perhaps only to proxy biological intermediates for which there are no known individual variants. Power calculations confirm the feasibility of extending our strategy to the analysis of tens of thousands of molecular phenotypes in large genome-wide meta-analyses. We conclude that our method represents a simple way in which potentially tens of thousands of molecular phenotypes could be screened for causal relationships with disease without having to expensively measure these variables in individual disease collections.

Identification of QTL regions and SSR markers associated with resistance to reniform nematode in Gossypium barbadense L. accession GB713.

PubMed

Gutiérrez, Osman A; Robinson, Arin F; Jenkins, Johnie N; McCarty, Jack C; Wubben, Martin J; Callahan, Franklin E; Nichols, Robert L

2011-02-01

The identification of molecular markers that are closely linked to gene(s) in Gossypium barbadense L. accession GB713 that confer a high level of resistance to reniform nematode (RN), Rotylenchulus reniformis Linford & Oliveira, would be very useful in cotton breeding programs. Our objectives were to determine the inheritance of RN resistance in the accession GB713, to identify SSR markers linked with RN resistance QTLs, and to map these linked markers to specific chromosomes. We grew and scored plants for RN reproduction in the P(1), P(2), F(1), F(2), BC(1)P(1), and BC(1)P(2) generations from the cross of GB713 × Acala Nem-X. The generation means analysis using the six generations indicated that one or more genes were involved in the RN resistance of GB713. The interspecific F(2) population of 300 plants was genotyped with SSR molecular markers that covered most of the chromosomes of Upland cotton (G. hirsutum L.). Results showed two QTLs on chromosome 21 and one QTL on chromosome 18. One QTL on chromosome 21 was at map position 168.6 (LOD 28.0) flanked by SSR markers, BNL 1551_162 and GH 132_199 at positions 154.2 and 177.3, respectively. A second QTL on chromosome 21 was at map position 182.7 (LOD 24.6) flanked by SSR markers BNL 4011_155 and BNL 3279_106 at positions 180.6 and 184.5, respectively. Our chromosome 21 map had 61 SSR markers covering 219 cM. One QTL with smaller genetic effects was localized to chromosome 18 at map position 39.6 (LOD 4.0) and flanked by SSR markers BNL 1721_178 and BNL 569_131 at positions 27.6 and 42.9, respectively. The two QTLs on chromosome 21 had significant additive and dominance effects, which were about equal for each QTL. The QTL on chromosome 18 showed larger additive than dominance effects. Following the precedent set by the naming of the G. longicalyx Hutchinson & Lee and G. aridum [(Rose & Standley) Skovsted] sources of resistance, we suggest the usage of Ren (barb1) and Ren (barb2) to designate these QTLs on chromosome 21 and Ren (barb3) on chromosome 18.

Molecular Classification Substitutes for the Prognostic Variables Stage, Age, and MYCN Status in Neuroblastoma Risk Assessment.

PubMed

Rosswog, Carolina; Schmidt, Rene; Oberthuer, André; Juraeva, Dilafruz; Brors, Benedikt; Engesser, Anne; Kahlert, Yvonne; Volland, Ruth; Bartenhagen, Christoph; Simon, Thorsten; Berthold, Frank; Hero, Barbara; Faldum, Andreas; Fischer, Matthias

2017-12-01

Current risk stratification systems for neuroblastoma patients consider clinical, histopathological, and genetic variables, and additional prognostic markers have been proposed in recent years. We here sought to select highly informative covariates in a multistep strategy based on consecutive Cox regression models, resulting in a risk score that integrates hazard ratios of prognostic variables. A cohort of 695 neuroblastoma patients was divided into a discovery set (n=75) for multigene predictor generation, a training set (n=411) for risk score development, and a validation set (n=209). Relevant prognostic variables were identified by stepwise multivariable L1-penalized least absolute shrinkage and selection operator (LASSO) Cox regression, followed by backward selection in multivariable Cox regression, and then integrated into a novel risk score. The variables stage, age, MYCN status, and two multigene predictors, NB-th24 and NB-th44, were selected as independent prognostic markers by LASSO Cox regression analysis. Following backward selection, only the multigene predictors were retained in the final model. Integration of these classifiers in a risk scoring system distinguished three patient subgroups that differed substantially in their outcome. The scoring system discriminated patients with diverging outcome in the validation cohort (5-year event-free survival, 84.9±3.4 vs 63.6±14.5 vs 31.0±5.4; P<.001), and its prognostic value was validated by multivariable analysis. We here propose a translational strategy for developing risk assessment systems based on hazard ratios of relevant prognostic variables. Our final neuroblastoma risk score comprised two multigene predictors only, supporting the notion that molecular properties of the tumor cells strongly impact clinical courses of neuroblastoma patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Conclusion of LOD-score analysis for family data generated under two-locus models.

PubMed Central

Dizier, M. H.; Babron, M. C.; Clerget-Darpoux, F.

1996-01-01

The power to detect linkage by the LOD-score method is investigated here for diseases that depend on the effects of two genes. The classical strategy is, first, to detect a major-gene (MG) effect by segregation analysis and, second, to seek for linkage with genetic markers by the LOD-score method using the MG parameters. We already showed that segregation analysis can lead to evidence for a MG effect for many two-locus models, with the estimates of the MG parameters being very different from those of the two genes involved in the disease. We show here that use of these MG parameter estimates in the LOD-score analysis may lead to a failure to detect linkage for some two-locus models. For these models, use of the sib-pair method gives a non-negligible increase of power to detect linkage. The linkage-homogeneity test among subsamples differing for the familial disease distribution provides evidence of parameter misspecification, when the MG parameters are used. Moreover, for most of the models, use of the MG parameters in LOD-score analysis leads to a large bias in estimation of the recombination fraction and sometimes also to a rejection of linkage for the true recombination fraction. A final important point is that a strong evidence of an MG effect, obtained by segregation analysis, does not necessarily imply that linkage will be detected for at least one of the two genes, even with the true parameters and with a close informative marker. PMID:8651311

Methods for detecting additional genes underlying Alzheimer disease

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

Locke, P.A.; Haines, J.L.; Ter-Minassian, M.

1994-09-01

Alzheimer`s disease (AD) is a complex inherited disorder with proven genetic heterogeneity. To date, genes on chromosome 21 (APP) and 14 (not yet identified) are associated with early-onset familial AD, while the APOE gene on chromosome 19 is associated with both late onset familial and sporadic AD and early onset sporadic AD. Although these genes likely account for the majority of AD, many familial cases cannot be traced to any of these genes. From a set of 127 late-onset multiplex families screened for APOE, 43 (34%) families have at least one affected individual with no APOE-4 allele, suggesting an alternativemore » genetic etiology. Simulation studies indicated that additional loci could be identified through a genomic screen with a 10 cM sieve on a subset of 21 well documented, non-APOE-4 families. Given the uncertainties in the mode of inheritance, reliance on a single analytical method could result in a missed linkage. Therefore, we have developed a strategy of using multiple overlapping yet complementary methods to detect linkage. These include sib-pair analysis and affected-pedigree-member analysis, neither of which makes assumptions about mode of inheritance, and lod score analysis (using two predefined genetic models). In order for a marker to qualify for follow-up, it must fit at least two of three criteria. These are nominal P values of 0.05 or less for the non-parametric methods, and/or a lod score greater than 1.0. Adjacent markers each fulfilling a single criterion also warrant follow-up. To date, we have screened 61 markers on chromosomes 1, 2, 3, 18, 19, 21, and 22. One marker, D2S163, generated a lod score of 1.06 ({theta} = 0.15) and an APMT statistic of 3.68 (P < 0.001). This region is currently being investigated in more detail. Updated results of this region plus additional screening data will be presented.« less

Improving selection of markers in nutrition research: evaluation of the criteria proposed by the ILSI Europe Marker Validation Initiative.

PubMed

Calder, Philip C; Boobis, Alan; Braun, Deborah; Champ, Claire L; Dye, Louise; Einöther, Suzanne; Greyling, Arno; Matthys, Christophe; Putz, Peter; Wopereis, Suzan; Woodside, Jayne V; Antoine, Jean-Michel

2017-06-01

The conduct of high-quality nutrition research requires the selection of appropriate markers as outcomes, for example as indicators of food or nutrient intake, nutritional status, health status or disease risk. Such selection requires detailed knowledge of the markers, and consideration of the factors that may influence their measurement, other than the effects of nutritional change. A framework to guide selection of markers within nutrition research studies would be a valuable tool for researchers. A multidisciplinary Expert Group set out to test criteria designed to aid the evaluation of candidate markers for their usefulness in nutrition research and subsequently to develop a scoring system for markers. The proposed criteria were tested using thirteen markers selected from a broad range of nutrition research fields. The result of this testing was a modified list of criteria and a template for evaluating a potential marker against the criteria. Subsequently, a semi-quantitative system for scoring a marker and an associated template were developed. This system will enable the evaluation and comparison of different candidate markers within the same field of nutrition research in order to identify their relative usefulness. The ranking criteria of proven, strong, medium or low are likely to vary according to research setting, research field and the type of tool used to assess the marker and therefore the considerations for scoring need to be determined in a setting-, field- and tool-specific manner. A database of such markers, their interpretation and range of possible values would be valuable to nutrition researchers.

The predictive value of noninvasive serum markers of liver fibrosis in patients with chronic hepatitis C.

PubMed

Gökcan, Hale; Kuzu, Ufuk Barış; Öztaş, Erkin; Saygılı, Fatih; Öztuna, Derya; Suna, Nuretdin; Tenlik, İlyas; Akdoğan, Meral; Kaçar, Sabite; Kılıç, Zeki Mesut Yalın; Kayaçetin, Ertuğrul

2016-03-01

This study aims to show the predictive value of noninvasive serum markers on the hepatic fibrosis level. This cross sectional study involves 120 patients with chronic hepatitis C. The noninvasive markers used were as follows: age-platelet index (AP index), cirrhosis discriminant score (CDS), aspartate aminotransferase (AST)-alanine aminotransferase (ALT) ratio (AAR), fibrosis-4 (FIB-4) index, AST-platelet ratio index (APRI), Goteborg University Cirrhosis Index (GUCI), FibroQ, King's score, platelet count. Concurrent liver biopsies were evaluated using the modified Ishak and Knodell scoring systems. In accordance with the Knodell scores, F3-F4 scores were defined as "severe fibrosis," and the modified Ishak scores stage of ≥3 (F3-F6) were defined as "clinically significant fibrosis." Receiver Operating Characteristic (ROC) curve analyses were carried out to compare the noninvasive markers with hepatic fibrosis level. Mean age of the patients was 51.7±11.6. A total of 10 patients (8.3%) with Knodell scores and 24 patients (20%) with modified Ishak scores were evaluated to have ≥F3 hepatic fibrosis. ROC analyses with the Knodell and modified Ishak scores were as follows: AP index=0.61-0.57, CDS=0.66-0.55, AAR=0.60-0.49, FIB-4=0.70-0.68, APRI=0.67-0.72, GUCI=0.66-0.72, FibroQ=0.64-0.54, King's score=0.68-0.54, platelet count=0.61-0.55. We found that APRI, FIB-4, King's score, and GUCI can be used to determination patients with mild fibrosis with a high negative predictive value and in the differentiation of severe/significant fibrosis from mild to moderate fibrosis.

ConGEMs: Condensed Gene Co-Expression Module Discovery Through Rule-Based Clustering and Its Application to Carcinogenesis.

PubMed

Mallik, Saurav; Zhao, Zhongming

2017-12-28

For transcriptomic analysis, there are numerous microarray-based genomic data, especially those generated for cancer research. The typical analysis measures the difference between a cancer sample-group and a matched control group for each transcript or gene. Association rule mining is used to discover interesting item sets through rule-based methodology. Thus, it has advantages to find causal effect relationships between the transcripts. In this work, we introduce two new rule-based similarity measures-weighted rank-based Jaccard and Cosine measures-and then propose a novel computational framework to detect condensed gene co-expression modules ( C o n G E M s) through the association rule-based learning system and the weighted similarity scores. In practice, the list of evolved condensed markers that consists of both singular and complex markers in nature depends on the corresponding condensed gene sets in either antecedent or consequent of the rules of the resultant modules. In our evaluation, these markers could be supported by literature evidence, KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway and Gene Ontology annotations. Specifically, we preliminarily identified differentially expressed genes using an empirical Bayes test. A recently developed algorithm-RANWAR-was then utilized to determine the association rules from these genes. Based on that, we computed the integrated similarity scores of these rule-based similarity measures between each rule-pair, and the resultant scores were used for clustering to identify the co-expressed rule-modules. We applied our method to a gene expression dataset for lung squamous cell carcinoma and a genome methylation dataset for uterine cervical carcinogenesis. Our proposed module discovery method produced better results than the traditional gene-module discovery measures. In summary, our proposed rule-based method is useful for exploring biomarker modules from transcriptomic data.

RNA-Seq identifies SNP markers for growth traits in rainbow trout.

PubMed

Salem, Mohamed; Vallejo, Roger L; Leeds, Timothy D; Palti, Yniv; Liu, Sixin; Sabbagh, Annas; Rexroad, Caird E; Yao, Jianbo

2012-01-01

Fast growth is an important and highly desired trait, which affects the profitability of food animal production, with feed costs accounting for the largest proportion of production costs. Traditional phenotype-based selection is typically used to select for growth traits; however, genetic improvement is slow over generations. Single nucleotide polymorphisms (SNPs) explain 90% of the genetic differences between individuals; therefore, they are most suitable for genetic evaluation and strategies that employ molecular genetics for selective breeding. SNPs found within or near a coding sequence are of particular interest because they are more likely to alter the biological function of a protein. We aimed to use SNPs to identify markers and genes associated with genetic variation in growth. RNA-Seq whole-transcriptome analysis of pooled cDNA samples from a population of rainbow trout selected for improved growth versus unselected genetic cohorts (10 fish from 1 full-sib family each) identified SNP markers associated with growth-rate. The allelic imbalances (the ratio between the allele frequencies of the fast growing sample and that of the slow growing sample) were considered at scores >5.0 as an amplification and <0.2 as loss of heterozygosity. A subset of SNPs (n = 54) were validated and evaluated for association with growth traits in 778 individuals of a three-generation parent/offspring panel representing 40 families. Twenty-two SNP markers and one mitochondrial haplotype were significantly associated with growth traits. Polymorphism of 48 of the markers was confirmed in other commercially important aquaculture stocks. Many markers were clustered into genes of metabolic energy production pathways and are suitable candidates for genetic selection. The study demonstrates that RNA-Seq at low sequence coverage of divergent populations is a fast and effective means of identifying SNPs, with allelic imbalances between phenotypes. This technique is suitable for marker development in non-model species lacking complete and well-annotated genome reference sequences.

A filtering method to generate high quality short reads using illumina paired-end technology.

PubMed

Eren, A Murat; Vineis, Joseph H; Morrison, Hilary G; Sogin, Mitchell L

2013-01-01

Consensus between independent reads improves the accuracy of genome and transcriptome analyses, however lack of consensus between very similar sequences in metagenomic studies can and often does represent natural variation of biological significance. The common use of machine-assigned quality scores on next generation platforms does not necessarily correlate with accuracy. Here, we describe using the overlap of paired-end, short sequence reads to identify error-prone reads in marker gene analyses and their contribution to spurious OTUs following clustering analysis using QIIME. Our approach can also reduce error in shotgun sequencing data generated from libraries with small, tightly constrained insert sizes. The open-source implementation of this algorithm in Python programming language with user instructions can be obtained from https://github.com/meren/illumina-utils.

A novel ultrasound-based vascular calcification score (CALCS) to detect subclinical atherosclerosis.

PubMed

Flore, R; Zocco, M A; Ainora, M E; Fonnesu, C; Nesci, A; Gasbarrini, A; Ponziani, F R

2018-02-01

To quantify non-coronary vascular calcifications (VC) in asymptomatic patients at low-intermediate cardiovascular risk by a new color Doppler ultrasound (DUS)-based score (the carotid, aortic, lower limbs calcium score, CALCs), and to correlate this score with classical parameters associated with cardiovascular risk [carotid intima media thickness (IMT), and arterial stiffness (AS)]. All consecutive asymptomatic patients who underwent a screening DUS of non-coronary circulation were evaluated and patients at low-intermediate cardiovascular risk were selected according to Framingham risk score (FRS). Among them, we enrolled 70 patients with US evidence of VC and 71 age, sex and FRS matched controls. The presence of VC was correlated with classical markers of cardiovascular risk, such as AS and intima-media thickness (IMT). AS, expressed as pulse wave velocity (PWV) and arterial distensibility, carotid IMT and CALCs were measured for both groups. AS and c-IMT were assessed by a new Radio-Frequency (RF) DUS-based method. CALCs was generated by our previously described B-mode DUS-based method according to number/size of VC in 11 non-coronary segments (range 0-33). Patients with VC presented higher AS and IMT values than controls (PWV 8.34±0.98 m/s vs. 6.74±0.68 m/s, p<0.0001; arterial distensibility 267±12 mm vs. 315±65 mm, p=0.001; IMT 687±132 mm vs. 572±91 mm, p<0.0001). Mean CALCs of patients with VC was 8.41±7.78. CALCs were significantly correlated with c-IMT (p<0.0001; r=0.3), PWV (p<0.0001; r=0.4) and arterial distensibility (p=0.002; r=-0.1). DUS-based CALCs is highly correlated with other validated markers of subclinical atherosclerosis, such as c-IMT and AS. Our results demonstrated the ability of CALCs to identify individual predictive factors beyond the traditional risk factors by quantifying an interesting and novel step of the atherogenic process. Future studies on larger series and with adequate follow up are necessary to confirm these results and to evaluate the role of this new marker in monitoring calcific atherosclerosis progression.

Linkage of familial Alzheimer disease to chromosome 14 in two large early-onset pedigrees: effects of marker allele frequencies on lod scores.

PubMed

Nechiporuk, A; Fain, P; Kort, E; Nee, L E; Frommelt, E; Polinsky, R J; Korenberg, J R; Pulst, S M

1993-05-01

Alzheimer disease (AD) is a devastating neurodegenerative disease leading to global dementia. In addition to sporadic forms of AD, familial forms (FAD) have been recognized. Mutations in the amyloid precursor protein (APP) gene on chromosome (CHR) 21 have been shown to cause early-onset AD in a small number of pedigrees. Recently, linkage to markers on CHR 14 has been established in several early-onset FAD pedigrees. We now report lod scores for CHR 14 markers in two large early-onset FAD pedigrees. Pairwise linkage analysis suggested that in these pedigrees the mutation is tightly linked to the loci D14S43 and D14S53. However, assumptions regarding marker allele frequencies had a major and often unpredictable effect on calculated lod scores. Therefore, caution needs to be exercised when single pedigrees are analyzed with marker allele frequencies determined from the literature or from a pool of spouses.

Tumor Cell-Free DNA Copy Number Instability Predicts Therapeutic Response to Immunotherapy.

PubMed

Weiss, Glen J; Beck, Julia; Braun, Donald P; Bornemann-Kolatzki, Kristen; Barilla, Heather; Cubello, Rhiannon; Quan, Walter; Sangal, Ashish; Khemka, Vivek; Waypa, Jordan; Mitchell, William M; Urnovitz, Howard; Schütz, Ekkehard

2017-09-01

Purpose: Chromosomal instability is a fundamental property of cancer, which can be quantified by next-generation sequencing (NGS) from plasma/serum-derived cell-free DNA (cfDNA). We hypothesized that cfDNA could be used as a real-time surrogate for imaging analysis of disease status as a function of response to immunotherapy and as a more reliable tool than tumor biomarkers. Experimental Design: Plasma cfDNA sequences from 56 patients with diverse advanced cancers were prospectively collected and analyzed in a single-blind study for copy number variations, expressed as a quantitative chromosomal number instability (CNI) score versus 126 noncancer controls in a training set of 23 and a blinded validation set of 33. Tumor biomarker concentrations and a surrogate marker for T regulatory cells (Tregs) were comparatively analyzed. Results: Elevated CNI scores were observed in 51 of 56 patients prior to therapy. The blinded validation cohort provided an overall prediction accuracy of 83% (25/30) and a positive predictive value of CNI score for progression of 92% (11/12). The combination of CNI score before cycle (Cy) 2 and 3 yielded a correct prediction for progression in all 13 patients. The CNI score also correctly identified cases of pseudo-tumor progression from hyperprogression. Before Cy2 and Cy3, there was no significant correlation for protein tumor markers, total cfDNA, or surrogate Tregs. Conclusions: Chromosomal instability quantification in plasma cfDNA can serve as an early indicator of response to immunotherapy. The method has the potential to reduce health care costs and disease burden for cancer patients following further validation. Clin Cancer Res; 23(17); 5074-81. ©2017 AACR . ©2017 American Association for Cancer Research.

Covariate analysis of late-onset Alzheimer disease refines the chromosome 12 locus.

PubMed

Liang, X; Schnetz-Boutaud, N; Kenealy, S J; Jiang, L; Bartlett, J; Lynch, B; Gaskell, P C; Gwirtsman, H; McFarland, L; Bembe, M L; Bronson, P; Gilbert, J R; Martin, E R; Pericak-Vance, M A; Haines, J L

2006-03-01

Alzheimer disease (AD) is a progressive neurodegenerative disorder of later life with a complex etiology and a strong genetic component. Several genomic screens have suggested that a region between chromosome 12p13 and 12q22 contains at least one additional locus underlying the susceptibility of AD. However, localization of this locus has been difficult. We performed a 5 cM microsatellite marker screen across 74 cM on chromosome 12 with 15 markers in 585 multiplex families consisting of 994 affected sibpairs and 213 other affected relative pairs. Analyses across the entire data set did not reveal significant evidence of linkage. However, suggestive linkage was observed in several subsets. In the 91 families where no affected individuals carry an ApoE varepsilon4 allele, an HLOD score of 1.55 was generated at D12S1042. We further examined the linkage data considering the proposed linkages to chromosome 9 (D9S741) and chromosome 10 (alpha-catenin gene). There was a modest (P=0.20) increase in the LOD score for D12S368 (MLOD=1.70) when using the D9S741 LOD scores as a covariate and a highly significant (P<0.001) increase in the MLOD score (4.19) for D12S1701 in autopsy-confirmed families (n=228) when using alpha-catenin LOD scores as a covariate. In both cases, families with no evidence of linkage to D9S741 or alpha-catenin demonstrated most of the evidence of linkage to chromosome 12, suggesting locus heterogeneity. Taken together, our data suggest that the 16 cM region between D12S1042 and D12S368 should be the subject of further detailed genomic efforts for the disease.

Integrating Multiple Data Sources for Combinatorial Marker Discovery: A Study in Tumorigenesis.

PubMed

Bandyopadhyay, Sanghamitra; Mallik, Saurav

2018-01-01

Identification of combinatorial markers from multiple data sources is a challenging task in bioinformatics. Here, we propose a novel computational framework for identifying significant combinatorial markers ( s) using both gene expression and methylation data. The gene expression and methylation data are integrated into a single continuous data as well as a (post-discretized) boolean data based on their intrinsic (i.e., inverse) relationship. A novel combined score of methylation and expression data (viz., ) is introduced which is computed on the integrated continuous data for identifying initial non-redundant set of genes. Thereafter, (maximal) frequent closed homogeneous genesets are identified using a well-known biclustering algorithm applied on the integrated boolean data of the determined non-redundant set of genes. A novel sample-based weighted support ( ) is then proposed that is consecutively calculated on the integrated boolean data of the determined non-redundant set of genes in order to identify the non-redundant significant genesets. The top few resulting genesets are identified as potential s. Since our proposed method generates a smaller number of significant non-redundant genesets than those by other popular methods, the method is much faster than the others. Application of the proposed technique on an expression and a methylation data for Uterine tumor or Prostate Carcinoma produces a set of significant combination of markers. We expect that such a combination of markers will produce lower false positives than individual markers.

TMA Navigator: network inference, patient stratification and survival analysis with tissue microarray data

PubMed Central

Lubbock, Alexander L. R.; Katz, Elad; Harrison, David J.; Overton, Ian M.

2013-01-01

Tissue microarrays (TMAs) allow multiplexed analysis of tissue samples and are frequently used to estimate biomarker protein expression in tumour biopsies. TMA Navigator (www.tmanavigator.org) is an open access web application for analysis of TMA data and related information, accommodating categorical, semi-continuous and continuous expression scores. Non-biological variation, or batch effects, can hinder data analysis and may be mitigated using the ComBat algorithm, which is incorporated with enhancements for automated application to TMA data. Unsupervised grouping of samples (patients) is provided according to Gaussian mixture modelling of marker scores, with cardinality selected by Bayesian information criterion regularization. Kaplan–Meier survival analysis is available, including comparison of groups identified by mixture modelling using the Mantel-Cox log-rank test. TMA Navigator also supports network inference approaches useful for TMA datasets, which often constitute comparatively few markers. Tissue and cell-type specific networks derived from TMA expression data offer insights into the molecular logic underlying pathophenotypes, towards more effective and personalized medicine. Output is interactive, and results may be exported for use with external programs. Private anonymous access is available, and user accounts may be generated for easier data management. PMID:23761446

Assignment of sockeye salmon (Oncorhynchus nerka) to spawning sites using DNA markers.

PubMed

Corley-Smith, Graham E; Wennerberg, Liv; Schembri, Joy A; Lim, Chinten J; Cooper, Karen L; Brandhorst, Bruce P

2005-01-01

Randomly amplified polymorphic DNA (RAPD) markers were used to assign individual adult sockeye salmon to their spawning sites using a genotype assignment test. Six primers were selected for use by screening bulked DNA samples for markers missing in fish from one or more of 5 sites in British Columbia or Alaska. Of 73 markers scored, 54 showed variation between or within sites among the sampled fish. Thirty-seven of the variable markers were not detected in any fish from one or more sites; 18 variable markers were detected in all fish from one or more other sites. Thus 25% of markers scored were found in all fish of some sites and in no fish of some other sites. An assignment test placed all 70 fish tested into their correct populations. Principal coordinate analysis of genetic variation produced clusters of fish corresponding to each sampling site. No sex-specific RAPD markers were detected among more than 1300 screened.

Nutritional risk assessment in critically ill cancer patients: systematic review

PubMed Central

Fruchtenicht, Ana Valéria Gonçalves; Poziomyck, Aline Kirjner; Kabke, Geórgia Brum; Loss, Sérgio Henrique; Antoniazzi, Jorge Luiz; Steemburgo, Thais; Moreira, Luis Fernando

2015-01-01

Objective To systematically review the main methods for nutritional risk assessment used in critically ill cancer patients and present the methods that better assess risks and predict relevant clinical outcomes in this group of patients, as well as to discuss the pros and cons of these methods according to the current literature. Methods The study consisted of a systematic review based on analysis of manuscripts retrieved from the PubMed, LILACS and SciELO databases by searching for the key words “nutritional risk assessment”, “critically ill” and “cancer”. Results Only 6 (17.7%) of 34 initially retrieved papers met the inclusion criteria and were selected for the review. The main outcomes of these studies were that resting energy expenditure was associated with undernourishment and overfeeding. The high Patient-Generated Subjective Global Assessment score was significantly associated with low food intake, weight loss and malnutrition. In terms of biochemical markers, higher levels of creatinine, albumin and urea were significantly associated with lower mortality. The worst survival was found for patients with worse Eastern Cooperative Oncologic Group - performance status, high Glasgow Prognostic Score, low albumin, high Patient-Generated Subjective Global Assessment score and high alkaline phosphatase levels. Geriatric Nutritional Risk Index values < 87 were significantly associated with mortality. A high Prognostic Inflammatory and Nutritional Index score was associated with abnormal nutritional status in critically ill cancer patients. Among the reviewed studies that examined weight and body mass index alone, no significant clinical outcome was found. Conclusion None of the methods reviewed helped to define risk among these patients. Therefore, assessment by a combination of weight loss and serum measurements, preferably in combination with other methods using scores such as Eastern Cooperative Oncologic Group - performance status, Glasgow Prognostic Score and Patient-Generated Subjective Global Assessment, is suggested given that their use is simple, feasible and useful in such cases. PMID:26270855

Applied immuno-epidemiological research: an approach for integrating existing knowledge into the statistical analysis of multiple immune markers.

PubMed

Genser, Bernd; Fischer, Joachim E; Figueiredo, Camila A; Alcântara-Neves, Neuza; Barreto, Mauricio L; Cooper, Philip J; Amorim, Leila D; Saemann, Marcus D; Weichhart, Thomas; Rodrigues, Laura C

2016-05-20

Immunologists often measure several correlated immunological markers, such as concentrations of different cytokines produced by different immune cells and/or measured under different conditions, to draw insights from complex immunological mechanisms. Although there have been recent methodological efforts to improve the statistical analysis of immunological data, a framework is still needed for the simultaneous analysis of multiple, often correlated, immune markers. This framework would allow the immunologists' hypotheses about the underlying biological mechanisms to be integrated. We present an analytical approach for statistical analysis of correlated immune markers, such as those commonly collected in modern immuno-epidemiological studies. We demonstrate i) how to deal with interdependencies among multiple measurements of the same immune marker, ii) how to analyse association patterns among different markers, iii) how to aggregate different measures and/or markers to immunological summary scores, iv) how to model the inter-relationships among these scores, and v) how to use these scores in epidemiological association analyses. We illustrate the application of our approach to multiple cytokine measurements from 818 children enrolled in a large immuno-epidemiological study (SCAALA Salvador), which aimed to quantify the major immunological mechanisms underlying atopic diseases or asthma. We demonstrate how to aggregate systematically the information captured in multiple cytokine measurements to immunological summary scores aimed at reflecting the presumed underlying immunological mechanisms (Th1/Th2 balance and immune regulatory network). We show how these aggregated immune scores can be used as predictors in regression models with outcomes of immunological studies (e.g. specific IgE) and compare the results to those obtained by a traditional multivariate regression approach. The proposed analytical approach may be especially useful to quantify complex immune responses in immuno-epidemiological studies, where investigators examine the relationship among epidemiological patterns, immune response, and disease outcomes.

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.

Sufficient Dimension Reduction for Longitudinally Measured Predictors

PubMed Central

Pfeiffer, Ruth M.; Forzani, Liliana; Bura, Efstathia

2013-01-01

We propose a method to combine several predictors (markers) that are measured repeatedly over time into a composite marker score without assuming a model and only requiring a mild condition on the predictor distribution. Assuming that the first and second moments of the predictors can be decomposed into a time and a marker component via a Kronecker product structure, that accommodates the longitudinal nature of the predictors, we develop first moment sufficient dimension reduction techniques to replace the original markers with linear transformations that contain sufficient information for the regression of the predictors on the outcome. These linear combinations can then be combined into a score that has better predictive performance than the score built under a general model that ignores the longitudinal structure of the data. Our methods can be applied to either continuous or categorical outcome measures. In simulations we focus on binary outcomes and show that our method outperforms existing alternatives using the AUC, the area under the receiver-operator characteristics (ROC) curve, as a summary measure of the discriminatory ability of a single continuous diagnostic marker for binary disease outcomes. PMID:22161635

Positive correlation between inflammation on sacroiliac joint MRI and serum C-terminal telopeptide of type-I collagen in ankylosing spondylitis but not in non-radiographic axial spondyloarthritis.

PubMed

Kang, Kwi Young; Jung, Joon-Yong; Hong, Yeon Sik; Ju, Ji Hyeon; Park, Sung-Hwan

2017-01-01

To identify the clinical disease activity scores and laboratory markers that best reflect magnetic resonance imaging (MRI)-determined sacroiliac joint (SIJ) inflammation in ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). This cross-sectional study included all consecutive patients who presented with axial spondyloarthritis in 2013-2015. All underwent SIJ MRI. The bone marrow oedema in the inflammatory lesions on MRI was scored using the SPondyloArthritis Research Consortium of Canada (SPARCC) method. Bone-specific alkaline phosphatase (BALP), serum C-terminal telopeptide of type-I collagen (sCTX-I), and inflammatory markers were measured. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) were assessed. The correlations between the MRI-determined SIJ inflammation scores and disease activity scores and laboratory variables were evaluated. Of the 81 patients with axSpA, 45 had AS and 36 had nr-axSpA. The AS and nr-axSpA groups did not differ in terms of disease activity scores, physical functional index, or MRI-determined SIJ inflammation. Erythrocyte sedimentation rate, C-reactive protein, and ASDAS correlated with MRI inflammatory scores in nr-axSpA but not in AS. sCTX-I correlated with MRI-determined SIJ inflammatory scores in AS only. BASDAI and BALP levels did not associate with MRI inflammatory scores in either group. Multivariate analysis showed that sCTX-I associated independently with MRI inflammatory score in AS (β=17.047, p=0.038). Inflammatory markers and ASDAS correlated with active sacroiliitis on MRI in nr-axSpA only. In AS, only sCTX-I correlated with active inflammation on SIJ MRI. sCTX-I may be useful as a marker of objective inflammation in AS.

Efficiency gain of marker-assisted backcrossing by sequentially increasing marker densities over generations.

PubMed

Prigge, Vanessa; Melchinger, Albrecht E; Dhillon, Baldev S; Frisch, Matthias

2009-06-01

Expenses for marker assays are the major costs in marker-assisted backcrossing programs for the transfer of target genes from a donor into the genetic background of a recipient genotype. Our objectives were to (1) investigate the effect of employing sequentially increasing marker densities over backcross generations on the recurrent parent genome (RPG) recovery and the number of marker data points (MDP) required, and (2) determine optimum designs for attaining RPG thresholds of 93-98% with a minimum number of MDP. We simulated the introgression of one dominant target gene for genome models of sugar beet (Beta vulgaris L.) and maize (Zea mays L.) with varying marker distances of 5-80 cM and population sizes of 30-250 plants across BC(1) to BC(3) generations. Employing less dense maps in early backcross generations resulted in savings of over 50% in the number of required MDP compared with using a constant set of markers and was accompanied only by small reductions in the attained RPG values. The optimum designs were characterized by increasing marker densities and increasing population sizes in advanced generations for both genome models. We conclude that increasing simultaneously the marker density and the population size from early to advanced backcross generations results in gene introgression with a minimum number of required MDP.

Fetal programming of infant neuromotor development: the generation R study.

PubMed

van Batenburg-Eddes, Tamara; de Groot, Laila; Steegers, Eric A P; Hofman, Albert; Jaddoe, Vincent W V; Verhulst, Frank C; Tiemeier, Henning

2010-02-01

The objective of the study was to examine whether infant neuromotor development is determined by fetal size and body symmetry in the general population. This study was embedded within the Generation R Study, a population-based cohort in Rotterdam. In 2965 fetuses, growth parameters were measured in mid-pregnancy and late pregnancy. After birth, at age 9 to 15 wks, neuromotor development was assessed with an adapted version of Touwen's Neurodevelopmental Examination. Less optimal neuromotor development was defined as a score in the highest tertile. We found that higher fetal weight was beneficial to infant neurodevelopment. A fetus with a 1-SD score higher weight in mid-pregnancy had an 11% lower risk of less optimal neuromotor development (OR: 0.89; 95% CI: 0.82-0.97). Similarly, a fetus with a 1-SD score larger abdominal-to-head circumference (AC/HC) ratio had a 13% lower risk of less optimal neuromotor development (OR: 0.87; 95% CI: 0.79-0.96). These associations were also present in late pregnancy. Our findings show that fetal size and body symmetry in pregnancy are associated with infant neuromotor development. These results suggest that differences in infant neuromotor development, a marker of behavioral and cognitive problems, are at least partly caused by processes occurring early in fetal life.

Power of a Labrador Retriever-Greyhound pedigree for linkage analysis of hip dysplasia and osteoarthritis.

PubMed

Todhunter, Rory J; Casella, George; Bliss, Stuart P; Lust, George; Williams, Alma Jo; Hamilton, Samuel; Dykes, Nathan L; Yeager, Amy E; Gilbert, Robert O; Burton-Wurster, Nancy I; Mellersh, Cathryn C; Acland, Gregory M

2003-04-01

To estimate the number of dogs required to find linkage to heritable traits of hip dysplasia in dogs from an experimental pedigree. 147 Labrador Retrievers, Greyhounds, and their crossbreed offspring. Labrador Retrievers with hip dysplasia were crossed with unaffected Greyhounds. Age at detection of femoral capital ossification, distraction index (DI), hip joint dorsolateral subluxation (DLS) score, and hip joint osteoarthritis (OA) were recorded. Power to find linkage of a single marker to a quantitative trait locus (QTL) controlling 100% of the variation in a dysplastic trait in the backcross dogs was determined. For the DI at the observed effect size, recombination fraction of 0.05, and heterozygosity of 0.75, 35 dogs in the backcross of the F1 to the Greyhound generation would yield linkage at a power of 0.8. For the DLS score, 35 dogs in the backcross to the Labrador Retriever generation would be required for linkage at the same power. For OSS, 45 dogs in the backcross to the founding Labrador Retrievers would yield linkage at the same power. Fewer dogs were projected to be necessary to find linkage to hip OA. Testing for linkage to the DLS at 4 loci simultaneously, each controlling 25% of the phenotypic variation, yielded an overall power of 0.7 CONCLUSIONS AND CLINICAL SIGNIFICANCE: Based on this conservative single-marker estimate, this pedigree has the requisite power to find microsatellites linked to susceptibility loci for hip dysplasia and hip OA by breeding a reasonable number of backcross dogs.

Neuropathology of SUDEP: Role of inflammation, blood-brain barrier impairment, and hypoxia.

PubMed

Michalak, Zuzanna; Obari, Dima; Ellis, Matthew; Thom, Maria; Sisodiya, Sanjay M

2017-02-07

To seek a neuropathologic signature of sudden unexpected death in epilepsy (SUDEP) in a postmortem cohort by use of immunohistochemistry for specific markers of inflammation, gliosis, acute neuronal injury due to hypoxia, and blood-brain barrier (BBB) disruption, enabling the generation of hypotheses about potential mechanisms of death in SUDEP. Using immunohistochemistry, we investigated the expression of 6 markers (CD163, human leukocyte antigen-antigen D related, glial fibrillary acid protein, hypoxia-inducible factor-1α [HIF-1α], immunoglobulin G, and albumin) in the hippocampus, amygdala, and medulla in 58 postmortem cases: 28 SUDEP (definite and probable), 12 epilepsy controls, and 18 nonepileptic sudden death controls. A semiquantitative measure of immunoreactivity was scored for all markers used, and quantitative image analysis was carried out for selected markers. Immunoreactivity was observed for all markers used within all studied brain regions and groups. Immunoreactivity for inflammatory reaction, BBB leakage, and HIF-1α in SUDEP cases was not different from that seen in control groups. This study represents a starting point to explore by immunohistochemistry the mechanisms underlying SUDEP in human brain tissue. Our approach highlights the potential and importance of considering immunohistochemical analysis to help identify biomarkers of SUDEP. Our results suggest that with the markers used, there is no clear immunohistochemical signature of SUDEP in human brain. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Surrogate endpoints in clinical trials of chronic kidney disease progression: moving from single to multiple risk marker response scores.

PubMed

Schievink, Bauke; Mol, Peter G M; Lambers Heerspink, Hiddo J

2015-11-01

There is increased interest in developing surrogate endpoints for clinical trials of chronic kidney disease progression, as the established clinically meaningful endpoint end-stage renal disease requires large and lengthy trials to assess drug efficacy. We describe recent developments in the search for novel surrogate endpoints. Declines in estimated glomerular filtration rate (eGFR) of 30% or 40% and albuminuria have been proposed as surrogates for end-stage renal disease. However, changes in eGFR or albuminuria may not be valid under all circumstances as drugs always have effects on multiple renal risk markers. Changes in each of these other 'off-target' risk markers can alter renal risk (either beneficially or adversely), and can thereby confound the relationship between surrogates that are based on single risk markers and renal outcome. Risk algorithms that integrate the short-term drug effects on multiple risk markers to predict drug effects on hard renal outcomes may therefore be more accurate. The validity of these risk algorithms is currently investigated. Given that drugs affect multiple renal risk markers, risk scores that integrate these effects are a promising alternative to using eGFR decline or albuminuria. Proper validation is required before these risk scores can be implemented.

A motion-compensated image filter for low-dose fluoroscopy in a real-time tumor-tracking radiotherapy system

PubMed Central

Miyamoto, Naoki; Ishikawa, Masayori; Sutherland, Kenneth; Suzuki, Ryusuke; Matsuura, Taeko; Toramatsu, Chie; Takao, Seishin; Nihongi, Hideaki; Shimizu, Shinichi; Umegaki, Kikuo; Shirato, Hiroki

2015-01-01

In the real-time tumor-tracking radiotherapy system, a surrogate fiducial marker inserted in or near the tumor is detected by fluoroscopy to realize respiratory-gated radiotherapy. The imaging dose caused by fluoroscopy should be minimized. In this work, an image processing technique is proposed for tracing a moving marker in low-dose imaging. The proposed tracking technique is a combination of a motion-compensated recursive filter and template pattern matching. The proposed image filter can reduce motion artifacts resulting from the recursive process based on the determination of the region of interest for the next frame according to the current marker position in the fluoroscopic images. The effectiveness of the proposed technique and the expected clinical benefit were examined by phantom experimental studies with actual tumor trajectories generated from clinical patient data. It was demonstrated that the marker motion could be traced in low-dose imaging by applying the proposed algorithm with acceptable registration error and high pattern recognition score in all trajectories, although some trajectories were not able to be tracked with the conventional spatial filters or without image filters. The positional accuracy is expected to be kept within ±2 mm. The total computation time required to determine the marker position is a few milliseconds. The proposed image processing technique is applicable for imaging dose reduction. PMID:25129556

Distribution and magnitude of type I error of model-based multipoint lod scores: implications for multipoint mod scores.

PubMed

Xing, Chao; Elston, Robert C

2006-07-01

The multipoint lod score and mod score methods have been advocated for their superior power in detecting linkage. However, little has been done to determine the distribution of multipoint lod scores or to examine the properties of mod scores. In this paper we study the distribution of multipoint lod scores both analytically and by simulation. We also study by simulation the distribution of maximum multipoint lod scores when maximized over different penetrance models. The multipoint lod score is approximately normally distributed with mean and variance that depend on marker informativity, marker density, specified genetic model, number of pedigrees, pedigree structure, and pattern of affection status. When the multipoint lod scores are maximized over a set of assumed penetrances models, an excess of false positive indications of linkage appear under dominant analysis models with low penetrances and under recessive analysis models with high penetrances. Therefore, caution should be taken in interpreting results when employing multipoint lod score and mod score approaches, in particular when inferring the level of linkage significance and the mode of inheritance of a trait.

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

PubMed

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

2018-06-01

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

Multiple marker abundance profiling: combining selected reaction monitoring and data-dependent acquisition for rapid estimation of organelle abundance in subcellular samples

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

Hooper, Cornelia M.; Stevens, Tim J.; Saukkonen, Anna

Measuring changes in protein or organelle abundance in the cell is an essential, but challenging aspect of cell biology. Frequently-used methods for determining organelle abundance typically rely on detection of a very few marker proteins, so are unsatisfactory. In silico estimates of protein abundances from publicly available protein spectra can provide useful standard abundance values but contain only data from tissue proteomes, and are not coupled to organelle localization data. A new protein abundance score, the normalized protein abundance scale (NPAS), expands on the number of scored proteins and the scoring accuracy of lower-abundance proteins in Arabidopsis. NPAS was combinedmore » with subcellular protein localization data, facilitating quantitative estimations of organelle abundance during routine experimental procedures. A suite of targeted proteomics markers for subcellular compartment markers was developed, enabling independent verification of in silico estimates for relative organelle abundance. Estimation of relative organelle abundance was found to be reproducible and consistent over a range of tissues and growth conditions. In silico abundance estimations and localization data have been combined into an online tool, multiple marker abundance profiling, available in the SUBA4 toolbox (http://suba.live).« less

Multiple marker abundance profiling: combining selected reaction monitoring and data-dependent acquisition for rapid estimation of organelle abundance in subcellular samples

DOE PAGES

Hooper, Cornelia M.; Stevens, Tim J.; Saukkonen, Anna; ...

2017-10-12

Measuring changes in protein or organelle abundance in the cell is an essential, but challenging aspect of cell biology. Frequently-used methods for determining organelle abundance typically rely on detection of a very few marker proteins, so are unsatisfactory. In silico estimates of protein abundances from publicly available protein spectra can provide useful standard abundance values but contain only data from tissue proteomes, and are not coupled to organelle localization data. A new protein abundance score, the normalized protein abundance scale (NPAS), expands on the number of scored proteins and the scoring accuracy of lower-abundance proteins in Arabidopsis. NPAS was combinedmore » with subcellular protein localization data, facilitating quantitative estimations of organelle abundance during routine experimental procedures. A suite of targeted proteomics markers for subcellular compartment markers was developed, enabling independent verification of in silico estimates for relative organelle abundance. Estimation of relative organelle abundance was found to be reproducible and consistent over a range of tissues and growth conditions. In silico abundance estimations and localization data have been combined into an online tool, multiple marker abundance profiling, available in the SUBA4 toolbox (http://suba.live).« less

Determining the linkage of disease-resistance genes to molecular markers: the LOD-SCORE method revisited with regard to necessary sample sizes.

PubMed

Hühn, M

1995-05-01

Some approaches to molecular marker-assisted linkage detection for a dominant disease-resistance trait based on a segregating F2 population are discussed. Analysis of two-point linkage is carried out by the traditional measure of maximum lod score. It depends on (1) the maximum-likelihood estimate of the recombination fraction between the marker and the disease-resistance gene locus, (2) the observed absolute frequencies, and (3) the unknown number of tested individuals. If one replaces the absolute frequencies by expressions depending on the unknown sample size and the maximum-likelihood estimate of recombination value, the conventional rule for significant linkage (maximum lod score exceeds a given linkage threshold) can be resolved for the sample size. For each sub-population used for linkage analysis [susceptible (= recessive) individuals, resistant (= dominant) individuals, complete F2] this approach gives a lower bound for the necessary number of individuals required for the detection of significant two-point linkage by the lod-score method.

Genetic diversity analysis of cyanogenic potential (CNp) of root among improved genotypes of cassava using simple sequence repeat markers.

PubMed

Moyib, O K; Mkumbira, J; Odunola, O A; Dixon, A G

2012-12-01

Cyanogenic potential (CNp) of cassava constitutes a serious problem for over 500 million people who rely on the crop as their main source of calories. Genetic diversity is a key to successful crop improvement for breeding new improved variability for target traits. Forty-three improved genotypes of cassava developed by International Institute of Tropical Agriculture (ITA), Ibadan, were characterized for CNp trait using 35 Simple Sequence.Repeat (SSR) markers. Essential colorimetry picric test was used for evaluation of CNp on a color scale of 1 to 14. The CNp scores obtained ranged from 3 to 9, with a mean score of 5.48 (+/- 0.09) based on Statistical Analysis System (SAS) package. TMS M98/ 0068 (4.0 +/- 0.25) was identified as the best genotype with low CNp while TMS M98/0028 (7.75 +/- 0.25) was the worst. The 43 genotypes were assigned into 7 phenotypic groups based on rank-sum analysis in SAS. Dissimilarity analysis representatives for windows generated a phylogenetic tree with 5 clusters which represented hybridizing groups. Each of the clusters (except 4) contained low CNp genotypes that could be used for improving the high CNp genotypes in the same or near cluster. The scatter plot of the genotypes showed that there was little or no demarcation for phenotypic CNp groupings in the molecular groupings. The result of this study demonstrated that SSR markers are powerful tools for the assessment of genetic variability, and proper identification and selection of parents for genetic improvement of low CNp trait among the IITA cassava collection.

Progression of urothelial carcinoma in situ of the urinary bladder: a switch from luminal to basal phenotype and related therapeutic implications.

PubMed

Barth, Isabella; Schneider, Ursula; Grimm, Tobias; Karl, Alexander; Horst, David; Gaisa, Nadine T; Knüchel, Ruth; Garczyk, Stefan

2018-05-01

The stratification of bladder cancer into luminal and basal tumors has recently been introduced as a novel prognostic system in patient cohorts of muscle-invasive bladder cancer or high-grade papillary carcinomas. Using a representative immunohistochemistry panel, we analyzed luminal and basal marker expression in a large case series (n = 156) of urothelial carcinoma in situ (CIS), a precancerous lesion that frequently progresses to muscle-invasive disease. The majority of CIS cases was characterized by a positivity for luminal markers (aberrant cytokeratin (CK) 20 85% (132/156), GATA3 median Remmele score (score of staining intensity (0-3) multiplied with percentage of positive cells (0-4)): 12, estrogen receptor (ER) β Remmele score > 2: 88% (138/156), human epidermal growth factor receptor 2 (Her2) Dako score 3+ 32% (50/156), Her2 Dako score 2+ 33% (51/156)), and marginal expression of basal markers (CK5/6+ 2% (3/156), CK14+ 1% (2/156)). To further investigate phenotypic stability during disease progression, we compared 48 pairs of CIS and invasive tumors from the same biopsy. A highly significant loss of luminal marker expression (p < 0.001) was observed in the course of progression whereas an increase of basal marker expression (p < 0.01) was noted in the invasive compartment. Importantly, 91% of CIS cases demonstrated a positivity for at least one of the two predictive markers Her2 and ERβ, indicating that the analysis of Her2 and ERβ may help to identify CIS-patient subgroups prone to more efficient targeted treatment strategies. Larger prospective and biomarker-embedded clinical trials are needed to confirm and validate our preliminary findings.

Tools for outcome prediction in patients with community acquired pneumonia.

PubMed

Khan, Faheem; Owens, Mark B; Restrepo, Marcos; Povoa, Pedro; Martin-Loeches, Ignacio

2017-02-01

Community-acquired pneumonia (CAP) is one of the most common causes of mortality world-wide. The mortality rate of patients with CAP is influenced by the severity of the disease, treatment failure and the requirement for hospitalization and/or intensive care unit (ICU) management, all of which may be predicted by biomarkers and clinical scoring systems. Areas covered: We review the recent literature examining the efficacy of established and newly-developed clinical scores, biological and inflammatory markers such as C-Reactive protein (CRP), procalcitonin (PCT) and Interleukin-6 (IL-6), whether used alone or in conjunction with clinical severity scores to assess the severity of CAP, predict treatment failure, guide acute in-hospital or ICU admission and predict mortality. Expert commentary: The early prediction of treatment failure using clinical scores and biomarkers plays a developing role in improving survival of patients with CAP by identifying high-risk patients requiring hospitalization or ICU admission; and may enable more efficient allocation of resources. However, it is likely that combinations of scoring systems and biomarkers will be of greater use than individual markers. Further larger studies are needed to corroborate the additive value of these markers to clinical prediction scores to provide a safer and more effective assessment tool for clinicians.

A comprehensive review of noninvasive liver fibrosis tests in pediatric nonalcoholic Fatty liver disease.

PubMed

Mansoor, Sana; Collyer, Elizabeth; Alkhouri, Naim

2015-06-01

Nonalcoholic fatty liver disease (NAFLD) and its spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and fibrosis have been increasing in the pediatric population. The presence and severity of fibrosis in patients with NAFLD are important prognostic factors for the risk of disease progression to cirrhosis. The gold standard for staging liver fibrosis is a liver biopsy. However, given the risks of this procedure, especially in the pediatric population, the development of noninvasive markers to diagnose and monitor progression of NAFLD is desirable. This paper will review recently developed noninvasive methods for diagnosing liver fibrosis in children with NAFLD. These include simple fibrosis scores, advanced biochemical markers, and radiologic imaging studies. Simple fibrosis scores use readily available laboratory tests; available one include AST/ALT ratio, AST to platelet ratio index (APRI), fibrosis (FIB)-4 index, NAFLD fibrosis score (NFS), pediatric NAFLD fibrosis index (PNFI), and pediatric NALFD fibrosis score (PNFS). Advanced biochemical markers include biomarkers of hepatocyte cell death such as cytokeratin 18 fragment levels, and markers of extracellular matrix turnover such as the Enhanced Liver Fibrosis (ELF) test and hyaluronic acid. Radiologic imaging studies estimate liver stiffness as a surrogate for liver fibrosis; these include transient elastography (TE), magnetic resonance elastography (MRE), and acoustic radiation force impulse imaging (ARFI).

Genomic scan for genes predisposing to schizophrenia

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

Coon, H.; Jensen. S.; Holik, J.

1994-03-15

We initiated a genome-wide search for genes predisposing to schizophrenia by ascertaining 9 families, each containing three to five cases of schizophrenia. The 9 pedigrees were initially genotyped with 329 polymorphic DNA loci distributed throughout the genome. Assuming either autosomal dominant or recessive inheritance, 254 DNA loci yielded lod scores less than -2.0 at {theta} = 0.0, 101 DNA markers gave lod scores less than -2.0 at {theta} = 0.05, while 5 DNA loci produced maximum lod scores greater than 1: D4S35, D14S17, D15S1, D22S84, and D22S55. Of the DNA markers yielding lod scores greater than 1, D4S35 and D22S55more » also were suggestive of linkage when the Affected-Pedigree-Member method was used. The families were then genotyped with four highly polymorphic simple sequence repeat markers; possible linkage diminished with DNA markers mapping nearby D4S35, while suggestive evidence of linkage remained with loci in the region of D22S55. Although follow-up investigation of these chromosomal regions may be warranted, our linkage results should be viewed as preliminary observations, as 35 unaffected persons are not past the age of risk. 90 refs., 3 tabs.« less

Long-term native liver fibrosis in biliary atresia: development of a novel scoring system using histology and standard liver tests.

PubMed

Tomita, Hirofumi; Masugi, Yohei; Hoshino, Ken; Fuchimoto, Yasushi; Fujino, Akihiro; Shimojima, Naoki; Ebinuma, Hirotoshi; Saito, Hidetsugu; Sakamoto, Michiie; Kuroda, Tatsuo

2014-06-01

Although liver fibrosis is an important predictor of outcomes for biliary atresia (BA), postsurgical native liver histology has not been well reported. Here, we retrospectively evaluated postsurgical native liver histology, and developed and assessed a novel scoring system - the BA liver fibrosis (BALF) score for non-invasively predicting liver fibrosis grades. We identified 259 native liver specimens from 91 BA patients. Of these, 180 specimens, obtained from 62 patients aged ≥1 year at examination, were used to develop the BALF scoring system. The BALF score equation was determined according to the prediction of histological fibrosis grades by multivariate ordered logistic regression analysis. The diagnostic powers of the BALF score and several non-invasive markers were assessed by area under the receiver operating characteristic curve (AUROC) analyses. Natural logarithms of the serum total bilirubin, γ-glutamyltransferase, and albumin levels, and age were selected as significantly independent variables for the BALF score equation. The BALF score had a good diagnostic power (AUROCs=0.86-0.94, p<0.001) and good diagnostic accuracy (79.4-93.3%) for each fibrosis grade. The BALF score revealed a strong correlation with fibrosis grade (r=0.77, p<0.001), and was the preferable non-invasive marker for diagnosing fibrosis grades ⩾F2. In a serial liver histology subgroup analysis, 7/15 patients exhibited liver fibrosis improvement with BALF scores being equivalent to histological fibrosis grades of F0-1. In postsurgical BA patients aged ⩾1year, the BALF score is a potential non-invasive marker of native liver fibrosis. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Association between Diet-Quality Scores, Adiposity, Total Cholesterol and Markers of Nutritional Status in European Adults: Findings from the Food4Me Study.

PubMed

Fallaize, Rosalind; Livingstone, Katherine M; Celis-Morales, Carlos; Macready, Anna L; San-Cristobal, Rodrigo; Navas-Carretero, Santiago; Marsaux, Cyril F M; O'Donovan, Clare B; Kolossa, Silvia; Moschonis, George; Walsh, Marianne C; Gibney, Eileen R; Brennan, Lorraine; Bouwman, Jildau; Manios, Yannis; Jarosz, Miroslaw; Martinez, J Alfredo; Daniel, Hannelore; Saris, Wim H M; Gundersen, Thomas E; Drevon, Christian A; Gibney, Michael J; Mathers, John C; Lovegrove, Julie A

2018-01-06

Diet-quality scores (DQS), which are developed across the globe, are used to define adherence to specific eating patterns and have been associated with risk of coronary heart disease and type-II diabetes. We explored the association between five diet-quality scores (Healthy Eating Index, HEI; Alternate Healthy Eating Index, AHEI; MedDietScore, MDS; PREDIMED Mediterranean Diet Score, P-MDS; Dutch Healthy Diet-Index, DHDI) and markers of metabolic health (anthropometry, objective physical activity levels (PAL), and dried blood spot total cholesterol (TC), total carotenoids, and omega-3 index) in the Food4Me cohort, using regression analysis. Dietary intake was assessed using a validated Food Frequency Questionnaire. Participants ( n = 1480) were adults recruited from seven European Union (EU) countries. Overall, women had higher HEI and AHEI than men ( p < 0.05), and scores varied significantly between countries. For all DQS, higher scores were associated with lower body mass index, lower waist-to-height ratio and waist circumference, and higher total carotenoids and omega-3-index ( p trends < 0.05). Higher HEI, AHEI, DHDI, and P-MDS scores were associated with increased daily PAL, moderate and vigorous activity, and reduced sedentary behaviour ( p trend < 0.05). We observed no association between DQS and TC. To conclude, higher DQS, which reflect better dietary patterns, were associated with markers of better nutritional status and metabolic health.

Validation of the high-throughput marker technology DArT using the model plant Arabidopsis thaliana.

PubMed

Wittenberg, Alexander H J; van der Lee, Theo; Cayla, Cyril; Kilian, Andrzej; Visser, Richard G F; Schouten, Henk J

2005-08-01

Diversity Arrays Technology (DArT) is a microarray-based DNA marker technique for genome-wide discovery and genotyping of genetic variation. DArT allows simultaneous scoring of hundreds of restriction site based polymorphisms between genotypes and does not require DNA sequence information or site-specific oligonucleotides. This paper demonstrates the potential of DArT for genetic mapping by validating the quality and molecular basis of the markers, using the model plant Arabidopsis thaliana. Restriction fragments from a genomic representation of the ecotype Landsberg erecta (Ler) were amplified by PCR, individualized by cloning and spotted onto glass slides. The arrays were then hybridized with labeled genomic representations of the ecotypes Columbia (Col) and Ler and of individuals from an F(2) population obtained from a Col x Ler cross. The scoring of markers with specialized software was highly reproducible and 107 markers could unambiguously be ordered on a genetic linkage map. The marker order on the genetic linkage map coincided with the order on the DNA sequence map. Sequencing of the Ler markers and alignment with the available Col genome sequence confirmed that the polymorphism in DArT markers is largely a result of restriction site polymorphisms.

Hemorrhage recurrence risk factors in cerebral amyloid angiopathy: Comparative analysis of the overall small vessel disease severity score versus individual neuroimaging markers.

PubMed

Boulouis, Gregoire; Charidimou, Andreas; Pasi, Marco; Roongpiboonsopit, Duangnapa; Xiong, Li; Auriel, Eitan; van Etten, Ellis S; Martinez-Ramirez, Sergi; Ayres, Alison; Vashkevich, Anastasia; Schwab, Kristin M; Rosand, Jonathan; Goldstein, Joshua N; Gurol, M Edip; Greenberg, Steven M; Viswanathan, Anand

2017-09-15

An MRI-based score of total small vessel disease burden (CAA-SVD-Score) in cerebral amyloid angiopathy (CAA) has been demonstrated to correlate with severity of pathologic changes. Evidence suggests that CAA-related intracerebral hemorrhage (ICH) recurrence risk is associated with specific disease imaging manifestations rather than overall severity. We compared the correlation between the CAA-SVD-Score with the risk of recurrent CAA-related lobar ICH versus the predictive role of each of its components. Consecutive patients with CAA-related ICH from a single-center prospective cohort were analyzed. Radiological markers of CAA related SVD damage were quantified and categorized according to the CAA-SVD-Score (0-6 points). Subjects were followed prospectively for recurrent symptomatic ICH. Adjusted Cox proportional hazards models were used to investigate associations between the CAA-SVD-Score as well as each of the individual MRI signatures of CAA and the risk of recurrent ICH. In 229 CAA patients with ICH, a total of 56 recurrent ICH events occurred during a median follow-up of 2.8years [IQR 0.9-5.4years, 781 person-years). Higher CAA-SVD-Score (HR=1.26 per additional point, 95%CI [1.04-1.52], p=0.015) and older age were independently associated with higher ICH recurrence risk. Analysis of individual markers of CAA showed that CAA-SVD-Score findings were due to the independent effect of disseminated superficial siderosis (HR for disseminated cSS vs none: 2.89, 95%CI [1.47-5.5], p=0.002) and high degree of perivascular spaces enlargement (RR=3.50-95%CI [1.04-21], p=0.042). In lobar CAA-ICH patients, higher CAA-SVD-Score does predict recurrent ICH. Amongst individual elements of the score, superficial siderosis and dilated perivascular spaces are the only markers independently associated with ICH recurrence, contributing to the evidence for distinct CAA phenotypes singled out by neuro-imaging manifestations. Copyright © 2017 Elsevier B.V. All rights reserved.

Interleukin-34 as a fibroblast-derived marker of liver fibrosis in patients with non-alcoholic fatty liver disease

PubMed Central

Shoji, Hirotaka; Yoshio, Sachiyo; Mano, Yohei; Kumagai, Erina; Sugiyama, Masaya; Korenaga, Masaaki; Arai, Taeang; Itokawa, Norio; Atsukawa, Masanori; Aikata, Hiroshi; Hyogo, Hideyuki; Chayama, Kazuaki; Ohashi, Tomohiko; Ito, Kiyoaki; Yoneda, Masashi; Nozaki, Yuichi; Kawaguchi, Takumi; Torimura, Takuji; Abe, Masanori; Hiasa, Yoichi; Fukai, Moto; Kamiyama, Toshiya; Taketomi, Akinobu; Mizokami, Masashi; Kanto, Tatsuya

2016-01-01

Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic non-viral liver disease. Activation of macrophages and hepatic stellate cells is a critical step that promotes liver fibrosis. We aimed to explore the feasibility of interleukin-34 (IL-34), a key regulator of macrophages, as a fibrosis marker in patients with NAFLD. We enrolled 197 liver biopsy-proven NAFLD patients. We evaluated the serum levels of IL-34, macrophage-colony stimulating factor (M-CSF), soluble CD163 (sCD163), 40 cytokines/chemokines, hyaluronic acid, type IV collagen 7s, and clinically-approved fibrosis scores. IL-34 increased with the progression of fibrosis and was an independent marker for liver fibrosis. Immunostaining experiments, using resected liver specimens from NAFLD patients, revealed that IL-34 was mainly expressed on liver fibroblasts. IL-34 based fibrosis score (0.0387*IL-34 (pg/ml) + 0.3623*type IV collagen 7s (ng/ml) + 0.0184*age (year)–1.1850) was a practical predictive model of liver fibrosis. Using receiver-operating characteristic analyses, the area under the curve, sensitivity, and specificity of IL-34 based fibrosis score were superior or comparable to the other fibrosis biomarkers and scores. In conclusion, the IL-34 based fibrosis score, including serum IL-34, type IV collagen 7s and age, is a feasible diagnostic marker of liver fibrosis in NAFLD patients. PMID:27363523

Noninvasive Tests Do Not Accurately Differentiate Nonalcoholic Steatohepatitis From Simple Steatosis: A Systematic Review and Meta-analysis.

PubMed

Verhaegh, Pauline; Bavalia, Roisin; Winkens, Bjorn; Masclee, Ad; Jonkers, Daisy; Koek, Ger

2018-06-01

Nonalcoholic fatty liver disease is a rapidly increasing health problem. Liver biopsy analysis is the most sensitive test to differentiate between nonalcoholic steatohepatitis (NASH) and simple steatosis (SS), but noninvasive methods are needed. We performed a systematic review and meta-analysis of noninvasive tests for differentiating NASH from SS, focusing on blood markers. We performed a systematic search of the PubMed, Medline and Embase (1990-2016) databases using defined keywords, limited to full-text papers in English and human adults, and identified 2608 articles. Two independent reviewers screened the articles and identified 122 eligible articles that used liver biopsy as reference standard. If at least 2 studies were available, pooled sensitivity (sens p ) and specificity (spec p ) values were determined using the Meta-Analysis Package for R (metafor). In the 122 studies analyzed, 219 different blood markers (107 single markers and 112 scoring systems) were identified to differentiate NASH from simple steatosis, and 22 other diagnostic tests were studied. Markers identified related to several pathophysiological mechanisms. The markers analyzed in the largest proportions of studies were alanine aminotransferase (sens p , 63.5% and spec p , 74.4%) within routine biochemical tests, adiponectin (sensp, 72.0% and spec p , 75.7%) within inflammatory markers, CK18-M30 (sens p , 68.4% and spec p , 74.2%) within markers of cell death or proliferation and homeostatic model assessment of insulin resistance (sens p , 69.0% and spec p , 72.7%) within the metabolic markers. Two scoring systems could also be pooled: the NASH test (differentiated NASH from borderline NASH plus simple steatosis with 22.9% sens p and 95.3% spec p ) and the GlycoNASH test (67.1% sens p and 63.8% spec p ). In the meta-analysis, we found no test to differentiate NASH from SS with a high level of pooled sensitivity and specificity (≥80%). However, some blood markers, when included in scoring systems in single studies, identified patients with NASH with ≥80% sensitivity and specificity. Replication studies and more standardized study designs are urgently needed. At present, no marker or scoring system can be recommended for use in clinical practice to differentiate NASH from simple steatosis. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

The effect of obesity on the rate of heparin-induced thrombocytopenia.

PubMed

Marler, Jacob L; Jones, G Morgan; Wheeler, Brian J; Alshaya, Abdulrahman; Hartmann, Jonathan L; Oliphant, Carrie S

2018-06-01

: Heparin-induced thrombocytopenia (HIT) occurs in patients receiving heparin-containing products due to the formation of platelet-activating antibodies to heparin and platelet factor 4. Diagnosis includes utilization of a scoring system known as the 4-T score, and HIT laboratory assays. Recently, obesity was identified as a potential factor associated with the development of HIT. The objective of this study was to evaluate the association of HIT with obesity in ICU and general medicine patients. We performed a chart review of adult patients within the Methodist Healthcare System, and included patients who had an ELISA and serotonin release assay laboratory tests reported within same hospital admission in which they also had documented receipt of heparin. Obese patients were compared with nonobese patients (BMI < 30) for the primary outcome of HIT occurrence, and secondary outcomes including rate of thrombosis, 4-T scores, and ELISA optical density values. We also generated a 5-T score by including one additional point for those with a BMI of 30 or more to determine the predictive value of this score in identifying HIT. Obesity was confirmed to be a risk factor for HIT, and the 5-T score model was also predictive of the development of HIT. However, the 5-T score was not statistically more predictive of HIT than the 4-T score. Predicting HIT remains challenging and novel markers of HIT are needed to improve HIT recognition. Although obesity did not improve the 4-T score, it may improve the predictability of other scoring systems, and further investigation is warranted.

[Preliminary linkage analysis of a Chinese family with benign familial infantile convulsion].

PubMed

Xiong, Ge; Deng, Fei-yan; Xiao, Bo; Yang, Xiao-su; Ning, Jing-chun; Wu, Zhi-guo; Wang, Kang; Deng, Hong-wen

2004-06-01

Benign familial infantile convulsions (BFIC) is a recently recognized autosomal dominant inherited disorder. This epileptic syndrome typically begins between 3 and 12 months of age with clusters of partial seizures in most cases and carries a good prognosis. So far, three loci have been linked to chromosome 19q12.1-13.1, chromosome 2q24 and chromosome 16p12-q12. The authors performed linkage analysis on this pedigree. A four-generation Chinese family was investigated. The total number of members was 32 in this family and two neurologists in Xiangya Hospital gave systemic physical examinations and interictal neurological examinations to nineteen members of this family. Venous blood samples were taken for genetic analysis. DNA was extracted from peripheral blood leukocytes using phenol-chloroform method. Seventeen microsatellite markers spanning the critical regions on chromosomes 19q12-13.1, 2q24, and 16p12-q12 were genotyped. These markers included D19S49, D19S250, D19S414, D19S416 and D19S245 for the 19q region, D2S2380, D2S399, D2S111, D2S2195, D2S2330 and D2S2345 for the 2q region, D16S401, D16S3131, D16S3093, D16S517, D16S3120 and D16S415 for the 16p-q region. The DNA from each sample was amplified for the 17 markers. After polymerase chain reactions (PCR), PCR products of chromosome 19 with markers D19S49, D19S250, D19S414, D19S416 and D19S245 were subjected to electrophoresis on 8% denatured polyacrylamide gel for at least 2 hours and 20 minutes. Then the length of the PCR products was judged in the Strategene Eagle Eye II automated gel image analyzer. For the markers from chromosome 2 and 16, PCR products were scanned at ABI 377 autosequencer. The data of PCR products were analyzed using the software Genescan v3.1, Genetyper v2.1 (Applied Biosystem, CA. USA) and GenoDB v1.0. After Mendelian checking, the eligible genotyping data were used for linkage analysis. LOD scores were calculated by using MLINK program of LINKAGE v5.1, under an assumption of autosomal dominant inheritance and the estimated penetrance was 0.9. The allele frequencies of each marker were assumed to be equal and the disease-allele frequencies were designated to be 1/10,000. The LOD scores were calculated at combination rate (theta) 0.0, 0.1, 0.2, 0.3, and 0.4. Among the 17 selected microsatellite markers, which cover the previously reported regions, seven markers' data (D16S3131, D16S517, D16S3120, D16S3093, D2S2380, D19S250 and D19S414) were omitted due to failed genotyping, low genetic heterogeneity, or failure to pass Mendelian checking. Omission of these markers was to ensure the reliability of our raw data. The two-point LOD scores were below zero for all the markers and the maximum LOD scores at theta = 0.0 were less than -2 for markers D19S49, D19S416, D19S245, D16S401, D16S415, D2S399, D2S111, D2S2195, D2S2330 and D2S2345. Thus, the linkage result showed no evidence that the disease locus is linked to any of these selected markers, which excludes the previously reported candidate regions found in other ethnic families. There is no evidence that this Chinese family was linked to one of the following loci: 19q12.1-13.1, 16p12-q12 and 2q24. The results indicated that BFIC showed genetic heterogeneity and the Chinese BFIC families might be mapped on another new locus.

Progression of MDS-UPDRS Scores Over Five Years in De Novo Parkinson Disease from the Parkinson's Progression Markers Initiative Cohort.

PubMed

Holden, Samantha K; Finseth, Taylor; Sillau, Stefan H; Berman, Brian D

2018-01-01

The Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UDPRS) is a commonly used tool to measure Parkinson disease (PD) progression. Longitudinal changes in MDS-UPDRS scores in de novo PD have not been established. Determine progression rates of MDS-UPDRS scores in de novo PD. 362 participants from the Parkinson's Progression Markers Initiative, a multicenter longitudinal cohort study of de novo PD, were included. Longitudinal progression of MDS-UPDRS total and subscale scores were modeled using mixed model regression. MDS-UPDRS scores increased in a linear fashion over five years in de novo PD. MDS-UPDRS total score increased an estimated 4.0 points/year, Part I 0.25 points/year, Part II 1.0 points/year, and Part III 2.4 points/year. The expected average progression of MDS-UPDRS scores in de novo PD from this study can assist in clinical monitoring and provide comparative data for detection of disease modification in treatment trials.

Estimation and test for linkage between markers: a comparison of lod score and χ (2) test in a linkage study of maritime pine (Pinus pinaster Ait.).

PubMed

Gerber, S; Rodolphe, F

1994-06-01

The first step in the construction of a linkage map involves the estimation and test for linkage between all possible pairs of markers. The lod score method is used in many linkage studies for the latter purpose. In contrast with classical statistical tests, this method does not rely on the choice of a first-type error level. We thus provide a comparison between the lod score and a χ (2) test on linkage data from a gymnosperm, the maritime pine. The lod score appears to be a very conservative test with the usual thresholds. Its severity depends on the type of data used.

Contribution for new genetic markers of rheumatoid arthritis activity and severity: sequencing of the tumor necrosis factor-alpha gene promoter.

PubMed

Fonseca, João Eurico; Cavaleiro, João; Teles, José; Sousa, Elsa; Andreozzi, Valeska L; Antunes, Marília; Amaral-Turkman, Maria A; Canhão, Helena; Mourão, Ana F; Lopes, Joana; Caetano-Lopes, Joana; Weinmann, Pamela; Sobral, Marta; Nero, Patrícia; Saavedra, Maria J; Malcata, Armando; Cruz, Margarida; Melo, Rui; Braña, Araceli; Miranda, Luis; Patto, José V; Barcelos, Anabela; da Silva, José Canas; Santos, Luís M; Figueiredo, Guilherme; Rodrigues, Mário; Jesus, Herberto; Quintal, Alberto; Carvalho, Teresa; da Silva, José A Pereira; Branco, Jaime; Queiroz, Mário Viana

2007-01-01

The objective of this study was to assess whether clinical measures of rheumatoid arthritis activity and severity were influenced by tumor necrosis factor-alpha (TNF-alpha) promoter genotype/haplotype markers. Each patient's disease activity was assessed by the disease activity score using 28 joint counts (DAS28) and functional capacity by the Health Assessment Questionnaire (HAQ) score. Systemic manifestations, radiological damage evaluated by the Sharp/van der Heijde (SvdH) score, disease-modifying anti-rheumatic drug use, joint surgeries, and work disability were also assessed. The promoter region of the TNF-alpha gene, between nucleotides -1,318 and +49, was sequenced using an automated platform. Five hundred fifty-four patients were evaluated and genotyped for 10 single-nucleotide polymorphism (SNP) markers, but 5 of these markers were excluded due to failure to fall within Hardy-Weinberg equilibrium or to monomorphism. Patients with more than 10 years of disease duration (DD) presented significant associations between the -857 SNP and systemic manifestations, as well as joint surgeries. Associations were also found between the -308 SNP and work disability in patients with more than 2 years of DD and radiological damage in patients with less than 10 years of DD. A borderline effect was found between the -238 SNP and HAQ score and radiological damage in patients with 2 to 10 years of DD. An association was also found between haplotypes and the SvdH score for those with more than 10 years of DD. An association was found between some TNF-alpha promoter SNPs and systemic manifestations, radiological progression, HAQ score, work disability, and joint surgeries, particularly in some classes of DD and between haplotypes and radiological progression for those with more than 10 years of DD.

Contribution for new genetic markers of rheumatoid arthritis activity and severity: sequencing of the tumor necrosis factor-alpha gene promoter

PubMed Central

Fonseca, João Eurico; Cavaleiro, João; Teles, José; Sousa, Elsa; Andreozzi, Valeska L; Antunes, Marília; Amaral-Turkman, Maria A; Canhão, Helena; Mourão, Ana F; Lopes, Joana; Caetano-Lopes, Joana; Weinmann, Pamela; Sobral, Marta; Nero, Patrícia; Saavedra, Maria J; Malcata, Armando; Cruz, Margarida; Melo, Rui; Braña, Araceli; Miranda, Luis; Patto, José V; Barcelos, Anabela; da Silva, José Canas; Santos, Luís M; Figueiredo, Guilherme; Rodrigues, Mário; Jesus, Herberto; Quintal, Alberto; Carvalho, Teresa; da Silva, José A Pereira; Branco, Jaime; Queiroz, Mário Viana

2007-01-01

The objective of this study was to assess whether clinical measures of rheumatoid arthritis activity and severity were influenced by tumor necrosis factor-alpha (TNF-α) promoter genotype/haplotype markers. Each patient's disease activity was assessed by the disease activity score using 28 joint counts (DAS28) and functional capacity by the Health Assessment Questionnaire (HAQ) score. Systemic manifestations, radiological damage evaluated by the Sharp/van der Heijde (SvdH) score, disease-modifying anti-rheumatic drug use, joint surgeries, and work disability were also assessed. The promoter region of the TNF-α gene, between nucleotides -1,318 and +49, was sequenced using an automated platform. Five hundred fifty-four patients were evaluated and genotyped for 10 single-nucleotide polymorphism (SNP) markers, but 5 of these markers were excluded due to failure to fall within Hardy-Weinberg equilibrium or to monomorphism. Patients with more than 10 years of disease duration (DD) presented significant associations between the -857 SNP and systemic manifestations, as well as joint surgeries. Associations were also found between the -308 SNP and work disability in patients with more than 2 years of DD and radiological damage in patients with less than 10 years of DD. A borderline effect was found between the -238 SNP and HAQ score and radiological damage in patients with 2 to 10 years of DD. An association was also found between haplotypes and the SvdH score for those with more than 10 years of DD. An association was found between some TNF-α promoter SNPs and systemic manifestations, radiological progression, HAQ score, work disability, and joint surgeries, particularly in some classes of DD and between haplotypes and radiological progression for those with more than 10 years of DD. PMID:17408492

Potential of Start Codon Targeted (SCoT) markers for DNA fingerprinting of newly synthesized tritordeums and their respective parents.

PubMed

Cabo, Sandra; Ferreira, Luciana; Carvalho, Ana; Martins-Lopes, Paula; Martín, António; Lima-Brito, José Eduardo

2014-08-01

Hexaploid tritordeum (H(ch)H(ch)AABB; 2n = 42) results from the cross between Hordeum chilense (H(ch)H(ch); 2n = 14) and cultivated durum wheat (Triticum turgidum ssp. durum (AABB; 2n = 28). Morphologically, tritordeum resembles the wheat parent, showing promise for agriculture and wheat breeding. Start Codon Targeted (SCoT) polymorphism is a recently developed technique that generates gene-targeted markers. Thus, we considered it interesting to evaluate its potential for the DNA fingerprinting of newly synthesized hexaploid tritordeums and their respective parents. In this study, 60 SCoT primers were tested, and 18 and 19 of them revealed SCoT polymorphisms in the newly synthesized tritordeum lines HT27 and HT22, respectively, and their parents. An analysis of the presence/absence of bands among tritordeums and their parents revealed three types of polymorphic markers: (i) shared by tritordeums and one of their parents, (ii) exclusively amplified in tritordeums, and (iii) exclusively amplified in the parents. No polymorphism was detected among individuals of each parental species. Three SCoT markers were exclusively amplified in tritordeums of lines HT22 and HT27, being considered as polyploidization-induced rearrangements. About 70% of the SCoT markers of H. chilense origin were not transmitted to the allopolyploids of both lines, and most of the SCoTs scored in the newly synthesized allopolyploids originated from wheat, reinforcing the potential use of tritordeum as an alternative crop.

A Diagnostic Marker to Discriminate Childhood Apraxia of Speech from Speech Delay: IV. the Pause Marker Index

ERIC Educational Resources Information Center

Shriberg, Lawrence D.; Strand, Edythe A.; Fourakis, Marios; Jakielski, Kathy J.; Hall, Sheryl D.; Karlsson, Heather B.; Mabie, Heather L.; McSweeny, Jane L.; Tilkens, Christie M.; Wilson, David L.

2017-01-01

Purpose: Three previous articles provided rationale, methods, and several forms of validity support for a diagnostic marker of childhood apraxia of speech (CAS), termed the pause marker (PM). Goals of the present article were to assess the validity and stability of the PM Index (PMI) to scale CAS severity. Method: PM scores and speech, prosody,…

A Diagnostic Marker to Discriminate Childhood Apraxia of Speech from Speech Delay: II. Validity Studies of the Pause Marker

ERIC Educational Resources Information Center

Shriberg, Lawrence D.; Strand, Edythe A.; Fourakis, Marios; Jakielski, Kathy J.; Hall, Sheryl D.; Karlsson, Heather B.; Mabie, Heather L.; McSweeny, Jane L.; Tilkens, Christie M.; Wilson, David L.

2017-01-01

Purpose: The purpose of this 2nd article in this supplement is to report validity support findings for the Pause Marker (PM), a proposed single-sign diagnostic marker of childhood apraxia of speech (CAS). Method: PM scores and additional perceptual and acoustic measures were obtained from 296 participants in cohorts with idiopathic and…

Cisgenic apple trees; development, characterization, and performance

PubMed Central

Krens, Frans A.; Schaart, Jan G.; van der Burgh, Aranka M.; Tinnenbroek-Capel, Iris E. M.; Groenwold, Remmelt; Kodde, Linda P.; Broggini, Giovanni A. L.; Gessler, Cesare; Schouten, Henk J.

2015-01-01

Two methods were developed for the generation of cisgenic apples. Both have been successfully applied producing trees. The first method avoids the use of any foreign selectable marker genes; only the gene-of-interest is integrated between the T-DNA border sequences. The second method makes use of recombinase-based marker excision. For the first method we used the MdMYB10 gene from a red-fleshed apple coding for a transcription factor involved in regulating anthocyanin biosynthesis. Red plantlets were obtained and presence of the cisgene was confirmed. Plantlets were grafted and grown in a greenhouse. After 3 years, the first flowers appeared, showing red petals. Pollination led to production of red-fleshed cisgenic apples. The second method used the pM(arker)F(ree) vector system, introducing the scab resistance gene Rvi6, derived from apple. Agrobacterium-mediated transformation, followed by selection on kanamycin, produced genetically modified apple lines. Next, leaves from in vitro material were treated to activate the recombinase leading to excision of selection genes. Subsequently, the leaf explants were subjected to negative selection for marker-free plantlets by inducing regeneration on medium containing 5-fluorocytosine. After verification of the marker-free nature, the obtained plants were grafted onto rootstocks. Young trees from four cisgenic lines and one intragenic line, all containing Rvi6, were planted in an orchard. Appropriate controls were incorporated in this trial. We scored scab incidence for three consecutive years on leaves after inoculations with Rvi6-avirulent strains. One cisgenic line and the intragenic line performed as well as the resistant control. In 2014 trees started to overcome their juvenile character and formed flowers and fruits. The first results of scoring scab symptoms on apple fruits were obtained. Apple fruits from susceptible controls showed scab symptoms, while fruits from cisgenic and intragenic lines were free of scab. PMID:25964793

Molecular mapping of QTLs for resistance to Gibberella ear rot, in corn, caused by Fusarium graminearum.

PubMed

Ali, M Liakat; Taylor, Jeff H; Jie, Liu; Sun, Genlou; William, Manilal; Kasha, Ken J; Reid, Lana M; Pauls, K Peter

2005-06-01

Gibberella ear rot, caused by the fungus Fusarium graminearum Schwabe, is a serious disease of corn (Zea mays) grown in northern climates. Infected corn is lower yielding and contains toxins that are dangerous to livestock and humans. Resistance to ear rot in corn is quantitative, specific to the mode of fungal entry (silk channels or kernel wounds), and highly influenced by the environment. Evaluations of ear rot resistance are complex and subjective; and they need to be repeated over several years. All of these factors have hampered attempts to develop F. graminearum resistant corn varieties. The aim of this study was to identify molecular markers linked to the genes for resistance to Gibberella ear rot. A recombinant inbred (RI) population, produced from a cross between a Gibberella ear rot resistant line (CO387) and a susceptible line (CG62), was field-inoculated and scored for Gibberella ear rot symptoms in the F4, F6, and F7 generations. The distributions of disease scores were continuous, indicating that resistance is probably conditioned by multiple loci. A molecular linkage map, based on segregation in the F5 RI population, contained 162 markers distributed over 10 linkage groups and had a total length of 2237 cM with an average distance between markers of 13.8 cM. Composite interval mapping identified 11 quantitative trait loci (QTLs) for Gibberella ear rot resistance following silk inoculation and 18 QTLs following kernel inoculation in 4 environments that accounted for 6.7%-35% of the total phenotypic variation. Only 2 QTLs (on linkage group 7) were detected in more than 1 test for silk resistance, and only 1 QTL (on linkage group 5) was detected in more than 1 test for kernel resistance, confirming the strong influence of the environment on these traits. The majority of the favorable alleles were derived from the resistant parent (CO387). The germplasm and markers for QTLs with significant phenotypic effects may be useful for marker-assisted selection to incorporate Gibberella ear rot resistance into commercial corn cultivars.

Cancer risk associated with chronic diseases and disease markers: prospective cohort study

PubMed Central

Tu, Huakang; Wen, Chi Pang; Tsai, Shan Pou; Chow, Wong-Ho; Wen, Christopher; Ye, Yuanqing; Zhao, Hua; Tsai, Min Kuang; Huang, Maosheng; Dinney, Colin P; Tsao, Chwen Keng

2018-01-01

Abstract Objectives To assess the independent and joint associations of major chronic diseases and disease markers with cancer risk and to explore the benefit of physical activity in reducing the cancer risk associated with chronic diseases and disease markers. Design Prospective cohort study. Setting Standard medical screening program in Taiwan. Participants 405 878 participants, for whom cardiovascular disease markers (blood pressure, total cholesterol, and heart rate), diabetes, chronic kidney disease markers (proteinuria and glomerular filtration rate), pulmonary disease, and gouty arthritis marker (uric acid) were measured or diagnosed according to standard methods, were followed for an average of 8.7 years. Main outcome measures Cancer incidence and cancer mortality. Results A statistically significantly increased risk of incident cancer was observed for the eight diseases and markers individually (except blood pressure and pulmonary disease), with adjusted hazard ratios ranging from 1.07 to 1.44. All eight diseases and markers were statistically significantly associated with risk of cancer death, with adjusted hazard ratios ranging from 1.12 to 1.70. Chronic disease risk scores summarizing the eight diseases and markers were positively associated with cancer risk in a dose-response manner, with the highest scores associated with a 2.21-fold (95% confidence interval 1.77-fold to 2.75-fold) and 4.00-fold (2.84-fold to 5.63-fold) higher cancer incidence and cancer mortality, respectively. High chronic disease risk scores were associated with substantial years of life lost, and the highest scores were associated with 13.3 years of life lost in men and 15.9 years of life lost in women. The population attributable fractions of cancer incidence or cancer mortality from the eight chronic diseases and markers together were comparable to those from five major lifestyle factors combined (cancer incidence: 20.5% v 24.8%; cancer mortality: 38.9% v 39.7%). Among physically active (versus inactive) participants, the increased cancer risk associated with chronic diseases and markers was attenuated by 48% for cancer incidence and 27% for cancer mortality. Conclusions Chronic disease is an overlooked risk factor for cancer, as important as five major lifestyle factors combined. In this study, chronic diseases contributed to more than one fifth of the risk for incident cancer and more than one third of the risk for cancer death. Physical activity is associated with a nearly 40% reduction in the cancer risk associated with chronic diseases. PMID:29386192

Cancer risk associated with chronic diseases and disease markers: prospective cohort study.

PubMed

Tu, Huakang; Wen, Chi Pang; Tsai, Shan Pou; Chow, Wong-Ho; Wen, Christopher; Ye, Yuanqing; Zhao, Hua; Tsai, Min Kuang; Huang, Maosheng; Dinney, Colin P; Tsao, Chwen Keng; Wu, Xifeng

2018-01-31

To assess the independent and joint associations of major chronic diseases and disease markers with cancer risk and to explore the benefit of physical activity in reducing the cancer risk associated with chronic diseases and disease markers. Prospective cohort study. Standard medical screening program in Taiwan. 405 878 participants, for whom cardiovascular disease markers (blood pressure, total cholesterol, and heart rate), diabetes, chronic kidney disease markers (proteinuria and glomerular filtration rate), pulmonary disease, and gouty arthritis marker (uric acid) were measured or diagnosed according to standard methods, were followed for an average of 8.7 years. Cancer incidence and cancer mortality. A statistically significantly increased risk of incident cancer was observed for the eight diseases and markers individually (except blood pressure and pulmonary disease), with adjusted hazard ratios ranging from 1.07 to 1.44. All eight diseases and markers were statistically significantly associated with risk of cancer death, with adjusted hazard ratios ranging from 1.12 to 1.70. Chronic disease risk scores summarizing the eight diseases and markers were positively associated with cancer risk in a dose-response manner, with the highest scores associated with a 2.21-fold (95% confidence interval 1.77-fold to 2.75-fold) and 4.00-fold (2.84-fold to 5.63-fold) higher cancer incidence and cancer mortality, respectively. High chronic disease risk scores were associated with substantial years of life lost, and the highest scores were associated with 13.3 years of life lost in men and 15.9 years of life lost in women. The population attributable fractions of cancer incidence or cancer mortality from the eight chronic diseases and markers together were comparable to those from five major lifestyle factors combined (cancer incidence: 20.5% v 24.8%; cancer mortality: 38.9% v 39.7%). Among physically active (versus inactive) participants, the increased cancer risk associated with chronic diseases and markers was attenuated by 48% for cancer incidence and 27% for cancer mortality. Chronic disease is an overlooked risk factor for cancer, as important as five major lifestyle factors combined. In this study, chronic diseases contributed to more than one fifth of the risk for incident cancer and more than one third of the risk for cancer death. Physical activity is associated with a nearly 40% reduction in the cancer risk associated with chronic diseases. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Targeted mapping and linkage analysis of morphological isozyme, and RAPD markers in peach.

PubMed

Chaparro, J X; Werner, D J; O'Malley, D; Sederoff, R R

1994-02-01

Nine different F2 families of peach [Prunus persica (L.) Batsch] were analyzed for linkage relationships between 14 morphological and two isozyme loci. Linkage was detected between weeping (We) and white flower (W), 33 cM; double flower (Dl) and pillar (Br), 10 cM; and flesh color (Y) and malate dehydrogenase (Mdh1), 26 cM. A leaf variant phenotypically distinct from the previously reported wavy-leaf (Wa) mutant in peach was found in progeny of 'Davie II'. The new willow-leaf character (designated Wa2) was closely linked (0.4 cM) to a new dwarf phenotype (designated Dw3). Two families derived from the pollen-fertile cultivar 'White Glory' segregated for pollen sterility, but segregation did not follow a 3∶1 ratio. Evidence is presented suggesting that 'White Glory' possesses a pollen-sterility gene (designated Ps2) that is non-allelic to the previously reported pollen-sterility gene (Ps) in peach. Ps2 was linked to both weeping (We-Ps2, 15.5 cM) and white flower (Ps2-W, 25.3 cM). A genomic map of peach containing 83 RAPD, one isozyme, and four morphological markers was generated using an F2 family obtained by selfing an NC174RL x 'Pillar' F1. A total of 83 RAPD markers were assigned to 15 linkage groups. Various RAPD markers were linked to morphological traits. Bulked segregant analysis was used to identify RAPD markers flanking the red-leaf (Gr) and Mdh1 loci in the NC174RL x 'Pillar' and 'Marsun' x 'White Glory' F2 families, respectively. Three markers flanking Mdh1 and ten markers flanking Gr were identified. The combination of RAPD markers and bulked segregant analysis provides an efficient method of identifying markers flanking traits of interest. Markers linked to traits that can only be scored late in development are potentially useful for marker-aided selection in trees. Alternatives for obtaining additional map order information for repulsion-phase markers in large F2 populations are proposed.

Apparent diffusion coefficient value is a strong predictor of unsuspected aggressiveness of prostate cancer before radical prostatectomy.

PubMed

Renard Penna, Raphaele; Cancel-Tassin, Geraldine; Comperat, Eva; Mozer, Pierre; Léon, Priscilla; Varinot, Justine; Roupret, Morgan; Bitker, Marc-Olivier; Lucidarme, Olivier; Cussenot, Olivier

2016-10-01

To evaluate the use of multiparametric MRI (mp MRI) parameters in order to predict prostate cancer aggressiveness as defined by pathological Gleason score or molecular markers in a cohort of patients defined with a Gleason score of 6 at biopsy. Sixty-seven men treated by radical prostatectomy (RP) for a low grade (Gleason 6) on biopsy and mp MRI before biopsy were selected. The cycle cell proliferation (CCP) score assessed by the Prolaris test and Ki-67/PTEN expression assessed by immunohistochemistry were quantified on the RP specimens. 49.25 % of the cancers were undergraded on biopsy compared to the RP specimens. Apparent diffusion coefficient (ADC) < 0.80 × 10(-3) mm(2)/s (P value 0.003), Likert score >4 (P value 0.003) and PSA density >0.15 ng/ml/cc (P value 0.035) were significantly associated with a higher RP Gleason score. Regarding molecular markers of aggressiveness, ADC < 0.80 × 10(-3) mm(2)/s and Likert score >4 were also significantly associated with a positive staining for Ki-67 (P value 0.039 and 0.01, respectively). No association was found between any analyzed MRI or clinical parameter and the CCP score. Decreasing ADC value is a stronger indicator of aggressive prostate cancer as defined by molecular markers or postsurgical histology than biopsy characteristics.

A Comparison Between Genotyping-by-sequencing and Array-based Scoring of SNPs for Genomic Prediction Accuracy in Winter Wheat

USDA-ARS?s Scientific Manuscript database

The utilization of DNA molecular markers in plant breeding to maximize selection response via marker assisted selection (MAS) and genomic selection (GS) has the potential to revolutionize plant breeding. A key factor affecting GS applicability is the choice of molecular marker platform. Genotypying-...

Bridging the Gap Between Large-scale Data Sets and Analyses: Semi-automated Methods to Facilitate Length Polymorphism Scoring and Data Analyses.

EPA Science Inventory

Amplified fragment length polymorphism (AFLP) markers can be developed more quickly and at a lower cost than microsatellite and single nucleotide polymorphism markers, which makes them ideal markers for large-scale studies of understudied taxa — such as species at risk. However,...

The relation between intensity and complexity of coronary artery lesion and oxidative stress in patients with acute coronary syndrome.

PubMed

Turan, Turhan; Menteşe, Ümit; Ağaç, Mustafa Tarık; Akyüz, Ali Rıza; Kul, Selim; Aykan, Ahmet Çağrı; Bektaş, Hüseyin; Korkmaz, Levent; Öztaş Menteşe, Seda; Dursun, İhsan; Çelik, Şükrü

2015-10-01

Oxidative stress plays a major role in the development of atherosclerosis. However, the relationship between oxidative stress and complexity and intensity of coronary artery disease is less clear. The aim of this study is to assess the relationship between oxidative stress markers and the complexity and intensity of coronary artery disease in patients with acute coronary syndrome (ACS). Sixty-seven consecutive patients with an early phase of ACS (<3 h) were included in this single-centre, cross-sectional, prospective study. Syntax and Gensini scores were calculated based on angiographic findings. Patients were divided into two CAD complexity groups according to their Syntax scores: low SYNTAX score (<22) and moderate to high SYNTAX score (>=22). Likewise patients were divided into two CAD severity groups according to the median Gensini score of 64: less intensive CAD with Gensini score (<64) and intensive CAD with Gensini score >=64. Blood samples were taken in 1 hour within administration in order to measure total oxidative status (TOS) and total antioxidant capacity (TAC) levels determined by Erel method. Oxidative stress index (OSI) was calculated by TOS /TAC. There was no significant difference between the two SYNTAX groups for oxidative stress markers. Median TOS and OSI values were significantly high in the intensive CAD group (p=0.005, p=0.04, respectively). The Gensini score was positively correlated with TOS and OSI (p=0.003, p=0.02, respectively). Oxidative stress markers may be considered supportive laboratory parameters related to CAD intensity but not complexity in ACS patients.

History by history statistical estimators in the BEAM code system.

PubMed

Walters, B R B; Kawrakow, I; Rogers, D W O

2002-12-01

A history by history method for estimating uncertainties has been implemented in the BEAMnrc and DOSXYznrc codes replacing the method of statistical batches. This method groups scored quantities (e.g., dose) by primary history. When phase-space sources are used, this method groups incident particles according to the primary histories that generated them. This necessitated adding markers (negative energy) to phase-space files to indicate the first particle generated by a new primary history. The new method greatly reduces the uncertainty in the uncertainty estimate. The new method eliminates one dimension (which kept the results for each batch) from all scoring arrays, resulting in memory requirement being decreased by a factor of 2. Correlations between particles in phase-space sources are taken into account. The only correlations with any significant impact on uncertainty are those introduced by particle recycling. Failure to account for these correlations can result in a significant underestimate of the uncertainty. The previous method of accounting for correlations due to recycling by placing all recycled particles in the same batch did work. Neither the new method nor the batch method take into account correlations between incident particles when a phase-space source is restarted so one must avoid restarts.

A new score for screening of malnutrition in patients with inoperable gastric adenocarcinoma.

PubMed

Esfahani, Ali; Somi, Mohammad Hossein; Asghari Jafarabadi, Mohammad; Ostadrahimi, Alireza; Ghayour Nahand, Mousa; Fathifar, Zahra; Doostzadeh, Akram; Ghoreishi, Zohreh

2017-06-01

Malnutrition is common in patients with gastric cancer. Early identification of malnourished patients results in improving quality of life. We aimed to assess the nutritional status of patients with inoperable gastric adenocarcinoma (IGA) and finding a precise malnutrition screening score for these patients before the onset of chemotherapy. Nutritional status was assessed using patient generated subjective global assessment (PG-SGA), visceral proteins, and high-sensitivity C reactive protein. Tumor markers of carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA-125) and CA 19-9 and their association with nutritional status were assessed. Then a new score for malnutrition screening was defined. Seventy-one patients with IGA completed the study. Malnourished and well-nourished patients (based on PG-SGA) were statistically different regarding albumin, prealbumin and CA-125. The best cut-off value for prealbumin for prediction of malnutrition was determined at 0.20 mg/dl and using known cut-off values for albumin (3.5 g/dl) and CA-125 (35 U/ml), a new score was defined for malnutrition screening named MS-score. According to MS-score, 92% of the patients had malnutrition and it could predict malnutrition with 96.8% sensitivity, 50% specificity and accuracy of 91.4%. MS-score has been suggested as an available and easy-to-use tool for malnutrition screening in patients with IGA. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Discerning morpho-anatomical, physiological and molecular multiformity in cultivated and wild genotypes of lentil with reconciliation to salinity stress

PubMed Central

Singh, Chandan Kumar; Kumari, Shanti; Singh Tomar, Ram Sewak; Karwa, Sourabh; Singh, Rajendra; Singh, Raja Bahadur; Sarkar, Susheel Kumar; Pal, Madan

2017-01-01

One hundred and sixty two genotypes of different Lens species were screened for salinity tolerance in hydroponics at 40, 80 and 120 mM sodium chloride (NaCl) for 30 d. The germination, seedling growth, biomass accumulation, seedling survivability, salinity scores, root and shoot anatomy, sodium ion (Na+), chloride ion (Cl-) and potassium ion (K+) concentrations, proline and antioxidant activities were measured to evaluate the performance of all the genotypes. The results were compared in respect of physiological (Na+, K+ and Cl-) and seed yield components obtained from field trials for salinity stress conducted during two years. Expression of salt tolerance in hydroponics was found to be reliable indicator for similarity in salt tolerance between genotypes and was evident in saline soil based comparisons. Impressive genotypic variation for salinity tolerance was observed among the genotypes screened under hydroponic and saline field conditions. Plant concentrations of Na+ and Cl- at 120 mM NaCl were found significantly correlated with germination, root and shoot length, fresh and dry weight of roots and shoots, seedling survivability, salinity scores and K+ under controlled conditions and ranked the genotypes along with their seed yield in the field. Root and shoot anatomy of tolerant line (PDL-1) and wild accession (ILWL-137) showed restricted uptake of Na+ and Cl- due to thick layer of their epidermis and endodermis as compared to sensitive cultigen (L-4076). All the genotypes were scanned using SSR markers for genetic diversity, which generated high polymorphism. On the basis of cluster analysis and population structure the contrasting genotypes were grouped into different classes. These markers may further be tested to explore their potential in marker-assisted selection. PMID:28542267

Molecular markers to complement sentinel node status in predicting survival in patients with high-risk locally invasive melanoma.

PubMed

Rowe, Casey J; Tang, Fiona; Hughes, Maria Celia B; Rodero, Mathieu P; Malt, Maryrose; Lambie, Duncan; Barbour, Andrew; Hayward, Nicholas K; Smithers, B Mark; Green, Adele C; Khosrotehrani, Kiarash

2016-08-01

Sentinel lymph node status is a major prognostic marker in locally invasive cutaneous melanoma. However, this procedure is not always feasible, requires advanced logistics and carries rare but significant morbidity. Previous studies have linked markers of tumour biology to patient survival. In this study, we aimed to combine the predictive value of established biomarkers in addition to clinical parameters as indicators of survival in addition to or instead of sentinel node biopsy in a cohort of high-risk melanoma patients. Patients with locally invasive melanomas undergoing sentinel lymph node biopsy were ascertained and prospectively followed. Information on mortality was validated through the National Death Index. Immunohistochemistry was used to analyse proteins previously reported to be associated with melanoma survival, namely Ki67, p16 and CD163. Evaluation and multivariate analyses according to REMARK criteria were used to generate models to predict disease-free and melanoma-specific survival. A total of 189 patients with available archival material of their primary tumour were analysed. Our study sample was representative of the entire cohort (N = 559). Average Breslow thickness was 2.5 mm. Thirty-two (17%) patients in the study sample died from melanoma during the follow-up period. A prognostic score was developed and was strongly predictive of survival, independent of sentinel node status. The score allowed classification of risk of melanoma death in sentinel node-negative patients. Combining clinicopathological factors and established biomarkers allows prediction of outcome in locally invasive melanoma and might be implemented in addition to or in cases when sentinel node biopsy cannot be performed. © 2016 UICC.

Exclusion of primary congenital glaucoma (PCG) from two candidate regions of chromosomes 1 and 6

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

Sarfarazi, M.; Akarsu, A.N.; Barsoum-Homsy, M.

1994-09-01

PCG is a genetically heterogeneous condition in which a significant proportion of families inherit in an autosomally recessive fashion. Although association of PCG with chromosomal abnormalities has been repeatedly reported in the literature, the chromosomal location of this condition is still unknown. Therefore, this study is designed to identify the chromosomal location of the PCG locus by positional mapping. We have identified 80 PCG families with a total of 261 potential informative meiosis. A group of 19 pedigrees with a minimum of 2 affected children in each pedigree and consanguinity in most of the parental generation were selected as ourmore » initial screening panel. This panel consists of a total of 44 affected and 93 unaffected individuals giving a total of 99 informative meiosis, including 5 phase-known. We used polymerase chain reaction (PCR), denaturing polyacrylamide gels and silver staining to genotype our families. We first screened for markers on 1q21-q31, the reported location for juvenile primary open-angle glaucoma and excluded a region of 30 cM as the likely site for the PCG locus. Association of PCG with both ring chromosome 6 and HLA-B8 has also been reported. Therefore, we genotyped our PCG panel with PCR applicable markers from 6p21. Significant negative lod scores were obtained for D6S105 (Z = -18.70) and D6S306 (Z = -5.99) at {theta}=0.001. HLA class 1 region has also contained one of the tubulin genes (TUBB) which is an obvious candidate for PCG. Study of this gene revealed a significant negative lod score with PCG (Z = -16.74, {theta}=0.001). A multipoint linkage analysis of markers in this and other regions containing the candidate genes will be presented.« less

Discerning morpho-anatomical, physiological and molecular multiformity in cultivated and wild genotypes of lentil with reconciliation to salinity stress.

PubMed

Singh, Dharmendra; Singh, Chandan Kumar; Kumari, Shanti; Singh Tomar, Ram Sewak; Karwa, Sourabh; Singh, Rajendra; Singh, Raja Bahadur; Sarkar, Susheel Kumar; Pal, Madan

2017-01-01

One hundred and sixty two genotypes of different Lens species were screened for salinity tolerance in hydroponics at 40, 80 and 120 mM sodium chloride (NaCl) for 30 d. The germination, seedling growth, biomass accumulation, seedling survivability, salinity scores, root and shoot anatomy, sodium ion (Na+), chloride ion (Cl-) and potassium ion (K+) concentrations, proline and antioxidant activities were measured to evaluate the performance of all the genotypes. The results were compared in respect of physiological (Na+, K+ and Cl-) and seed yield components obtained from field trials for salinity stress conducted during two years. Expression of salt tolerance in hydroponics was found to be reliable indicator for similarity in salt tolerance between genotypes and was evident in saline soil based comparisons. Impressive genotypic variation for salinity tolerance was observed among the genotypes screened under hydroponic and saline field conditions. Plant concentrations of Na+ and Cl- at 120 mM NaCl were found significantly correlated with germination, root and shoot length, fresh and dry weight of roots and shoots, seedling survivability, salinity scores and K+ under controlled conditions and ranked the genotypes along with their seed yield in the field. Root and shoot anatomy of tolerant line (PDL-1) and wild accession (ILWL-137) showed restricted uptake of Na+ and Cl- due to thick layer of their epidermis and endodermis as compared to sensitive cultigen (L-4076). All the genotypes were scanned using SSR markers for genetic diversity, which generated high polymorphism. On the basis of cluster analysis and population structure the contrasting genotypes were grouped into different classes. These markers may further be tested to explore their potential in marker-assisted selection.

Mitochondrial DNA Marker EST00083 Is Not Associated with High vs. Average IQ in a German Sample.

ERIC Educational Resources Information Center

Moises, Hans W.; Yang, Liu; Kohnke, Michael; Vetter, Peter; Neppert, Jurgen; Petrill, Stephen A.; Plomin, Robert

1998-01-01

Tested the association of a mitochondrial DNA marker (EST00083) with high IQ in a sample of 47 German adults with high IQ scores and 77 adults with IQs estimated at lower than 110. Results do not support the hypothesis that high IQ is associated with this marker. (SLD)

Hereditary motor and sensory neuropathy with proximal dominancy in the lower extremities, urinary disturbance, and paroxysmal dry cough.

PubMed

Miura, Shiroh; Shibata, Hiroki; Kida, Hiroshi; Noda, Kazuhito; Tomiyasu, Katsuro; Yamamoto, Ken; Iwaki, Akiko; Ayabe, Mitsuyoshi; Aizawa, Hisamichi; Taniwaki, Takayuki; Fukumaki, Yasuyuki

2008-10-15

We studied a four-generation pedigree of a Japanese family with hereditary neuropathy to elucidate the genetic basis of this disease. Twelve members of the family were enrolled in this study. The clinical features were neurogenic muscle weakness with proximal dominancy in the lower extremities, sensory involvement, areflexia, fine postural tremors, painful muscle cramps, elevated creatine kinase levels, recurrent paroxysmal dry cough, and neurogenic bladder. We performed a genome-wide search using genetic loci spaced at about 13 Mb intervals. Although nine chromosomes (1, 3, 4, 5, 6, 10, 17, 19, and 22) had at least one region in which the logarithm of odds (LOD) score was over 1.0, no loci fulfilled the criteria for significant evidence of linkage. Moreover, we analyzed an extra 14 markers on 3p12-q13 (the locus of hereditary motor and sensory neuropathy, proximal dominant form) and an extra five markers on 3p22-p24 (the locus of hereditary sensory neuropathy with chronic cough) and observed LOD scores of <-3 on both 3p12-q13 and 3p22-p24. Mutation scanning of the entire coding regions of the MPZ and PMP22 genes revealed no mutations. We conclude that the disorder described here is a newly classified hereditary motor and sensory neuropathy with autosomal dominant inheritance.

Diversity Arrays Technology (DArT) for whole-genome profiling of barley

PubMed Central

Wenzl, Peter; Carling, Jason; Kudrna, David; Jaccoud, Damian; Huttner, Eric; Kleinhofs, Andris; Kilian, Andrzej

2004-01-01

Diversity Arrays Technology (DArT) can detect and type DNA variation at several hundred genomic loci in parallel without relying on sequence information. Here we show that it can be effectively applied to genetic mapping and diversity analyses of barley, a species with a 5,000-Mbp genome. We tested several complexity reduction methods and selected two that generated the most polymorphic genomic representations. Arrays containing individual fragments from these representations generated DArT fingerprints with a genotype call rate of 98.0% and a scoring reproducibility of at least 99.8%. The fingerprints grouped barley lines according to known genetic relationships. To validate the Mendelian behavior of DArT markers, we constructed a genetic map for a cross between cultivars Steptoe and Morex. Nearly all polymorphic array features could be incorporated into one of seven linkage groups (98.8%). The resulting map comprised ≈385 unique DArT markers and spanned 1,137 centimorgans. A comparison with the restriction fragment length polymorphism-based framework map indicated that the quality of the DArT map was equivalent, if not superior, to that of the framework map. These results highlight the potential of DArT as a generic technique for genome profiling in the context of molecular breeding and genomics. PMID:15192146

Investigating daily fatigue scores during two-week offshore day shifts.

PubMed

Riethmeister, Vanessa; Bültmann, Ute; Gordijn, Marijke; Brouwer, Sandra; de Boer, Michiel

2018-09-01

This study examined daily scores of fatigue and circadian rhythm markers over two-week offshore day shift periods. A prospective cohort study among N = 60 offshore day-shift workers working two-week offshore shifts was conducted. Offshore day shifts lasted from 07:00 - 19:00 h. Fatigue was measured objectively with pre- and post-shift scores of the 3-minute psychomotor vigilance tasks (PVT-B) parameters (reaction times, number of lapses, errors and false starts) and subjectively with pre- and post-shift Karolinska Sleepiness Scale (KSS) ratings. Evening saliva samples were collected on offshore days 2,7 and 13 to measure circadian rhythm markers such as dim-light melatonin onset times and cortisol. Generalized and linear mixed model analyses were used to examine daily fatigue scores over time. Complete data from N = 42 offshore day shift workers was analyzed. Daily parameters of objective fatigue, PVT-B scores (reaction times, average number of lapses, errors and false starts), remained stable over the course of the two-week offshore day shifts. Daily subjective post-shift fatigue scores significantly increased over the course of the two-week offshore shifts. Each day offshore was associated with an increased post-shift subjective fatigue score of 0.06 points (95%CI: .03 - .09 p < .001). No significant statistical differences in subjective pre-shift fatigue scores were found. Neither a circadian rhythm phase shift of melatonin nor an effect on the pattern and levels of evening cortisol was found. Daily parameters of objective fatigue scores remained stable over the course of the two-week offshore day shifts. Daily subjective post-shift fatigue scores significantly increased over the course of the two-week offshore shifts. No significant changes in circadian rhythm markers were found. Increased post-shift fatigue scores, especially during the last days of an offshore shift, should be considered and managed in (offshore) fatigue risk management programs and fatigue risk prediction models. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cross-parent reliability in rating ASD markers in infants.

PubMed

Ben-Sasson, Ayelet; Amit-Ben-Simhon, Hemda; Meyer, Sonya

2015-06-01

To investigate the congruence and discrepancies between mother and father reports of early autism spectrum disorders (ASD) markers. Mothers (n = 80) and fathers (n = 78) of 12-month-old infants (55% boys) completed the first year inventory (FYI), an ASD norm-referenced screening questionnaire. Mothers also completed the Infant Toddler Social Emotional Assessment (ITSEA). There were significant and moderate intra-class correlations between mother and father reports for most FYI factors. Fathers' median FYI social-communication domain score was almost twice that of mothers. Mann-Whitney tests indicated that fathers rated their child significantly higher than mothers on the four FYI social-communication factors and on the sensory processing factor. Linear weighted kappa analyses indicated poor agreement on gaze-related and reactivity FYI items. FYI social-communication and sensory-regulatory factors showed significant correlations with corresponding ITSEA scores. Social-communication markers pose a greater challenge for consistent report across parents than sensory-regulatory markers.

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.

Two-trait-locus linkage analysis: A powerful strategy for mapping complex genetic traits

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

Schork, N.J.; Boehnke, M.; Terwilliger, J.D.

1993-11-01

Nearly all diseases mapped to date follow clear Mendelian, single-locus segregation patterns. In contrast, many common familial diseases such as diabetes, psoriasis, several forms of cancer, and schizophrenia are familial and appear to have a genetic component but do not exhibit simple Mendelian transmission. More complex models are required to explain the genetics of these important diseases. In this paper, the authors explore two-trait-locus, two-marker-locus linkage analysis in which two trait loci are mapped simultaneously to separate genetic markers. The authors compare the utility of this approach to standard one-trait-locus, one-marker-locus linkage analysis with and without allowance for heterogeneity. Themore » authors also compare the utility of the two-trait-locus, two-marker-locus analysis to two-trait-locus, one-marker-locus linkage analysis. For common diseases, pedigrees are often bilineal, with disease genes entering via two or more unrelated pedigree members. Since such pedigrees often are avoided in linkage studies, the authors also investigate the relative information content of unilineal and bilineal pedigrees. For the dominant-or-recessive and threshold models that the authors consider, the authors find that two-trait-locus, two-marker-locus linkage analysis can provide substantially more linkage information, as measured by expected maximum lod score, than standard one-trait-locus, one-marker-locus methods, even allowing for heterogeneity, while, for a dominant-or-dominant generating model, one-locus models that allow for heterogeneity extract essentially as much information as the two-trait-locus methods. For these three models, the authors also find that bilineal pedigrees provide sufficient linkage information to warrant their inclusion in such studies. The authors discuss strategies for assessing the significance of the two linkages assumed in two-trait-locus, two-marker-locus models. 37 refs., 1 fig., 4 tabs.« less

Nance-Horan syndrome: localization within the region Xp21.1-Xp22.3 by linkage analysis.

PubMed

Stambolian, D; Lewis, R A; Buetow, K; Bond, A; Nussbaum, R

1990-07-01

Nance-Horan Syndrome (NHS) or X-linked cataract-dental syndrome (MIM 302350) is a disease of unknown pathogenesis characterized by congenital cataracts and dental anomalies. We performed linkage analysis in three kindreds with NHS by using six RFLP markers between Xp11.3 and Xp22.3. Close linkage was found between NHS and polymorphic loci DXS43 (theta = 0 with lod score 2.89), DXS41 (theta = 0 with lod score 3.44), and DXS67 (theta = 0 with lod score 2.74), defined by probes pD2, p99-6, and pB24, respectively. Recombinations were found with the marker loci DXS84 (theta = .04 with lod score 4.13), DXS143 (theta = .06 with lod score 3.11) and DXS7 (theta = .09 with lod score 1.68). Multipoint linkage analysis determined the NHS locus to be linked completely to DXS41 (lod score = 7.07). Our linkage results, combined with analysis of Xp interstitial deletions, suggest that the NHS locus is located within or close to the Xp22.1-Xp22.2 region.

Nance-Horan syndrome: localization within the region Xp21.1-Xp22.3 by linkage analysis.

PubMed Central

Stambolian, D; Lewis, R A; Buetow, K; Bond, A; Nussbaum, R

1990-01-01

Nance-Horan Syndrome (NHS) or X-linked cataract-dental syndrome (MIM 302350) is a disease of unknown pathogenesis characterized by congenital cataracts and dental anomalies. We performed linkage analysis in three kindreds with NHS by using six RFLP markers between Xp11.3 and Xp22.3. Close linkage was found between NHS and polymorphic loci DXS43 (theta = 0 with lod score 2.89), DXS41 (theta = 0 with lod score 3.44), and DXS67 (theta = 0 with lod score 2.74), defined by probes pD2, p99-6, and pB24, respectively. Recombinations were found with the marker loci DXS84 (theta = .04 with lod score 4.13), DXS143 (theta = .06 with lod score 3.11) and DXS7 (theta = .09 with lod score 1.68). Multipoint linkage analysis determined the NHS locus to be linked completely to DXS41 (lod score = 7.07). Our linkage results, combined with analysis of Xp interstitial deletions, suggest that the NHS locus is located within or close to the Xp22.1-Xp22.2 region. PMID:1971992

Diffusion tensor image segmentation of the cerebrum provides a single measure of cerebral small vessel disease severity related to cognitive change.

PubMed

Williams, Owen A; Zeestraten, Eva A; Benjamin, Philip; Lambert, Christian; Lawrence, Andrew J; Mackinnon, Andrew D; Morris, Robin G; Markus, Hugh S; Charlton, Rebecca A; Barrick, Thomas R

2017-01-01

Cerebral small vessel disease (SVD) is the primary cause of vascular cognitive impairment and is associated with decline in executive function (EF) and information processing speed (IPS). Imaging biomarkers are needed that can monitor and identify individuals at risk of severe cognitive decline. Recently there has been interest in combining several magnetic resonance imaging (MRI) markers of SVD into a unitary score to describe disease severity. Here we apply a diffusion tensor image (DTI) segmentation technique (DSEG) to describe SVD related changes in a single unitary score across the whole cerebrum, to investigate its relationship with cognitive change over a three-year period. 98 patients (aged 43-89) with SVD underwent annual MRI scanning and cognitive testing for up to three years. DSEG provides a vector of 16 discrete segments describing brain microstructure of healthy and/or damaged tissue. By calculating the scalar product of each DSEG vector in reference to that of a healthy ageing control we generate an angular measure (DSEG θ ) describing the patients' brain tissue microstructural similarity to a disease free model of a healthy ageing brain. Conventional MRI markers of SVD brain change were also assessed including white matter hyperintensities, cerebral atrophy, incident lacunes, cerebral-microbleeds, and white matter microstructural damage measured by DTI histogram parameters. The impact of brain change on cognition was explored using linear mixed-effects models. Post-hoc sample size analysis was used to assess the viability of DSEG θ as a tool for clinical trials. Changes in brain structure described by DSEG θ were related to change in EF and IPS ( p  < 0.001) and remained significant in multivariate models including other MRI markers of SVD as well as age, gender and premorbid IQ. Of the conventional markers, presence of new lacunes was the only marker to remain a significant predictor of change in EF and IPS in the multivariate models ( p  = 0.002). Change in DSEG θ was also related to change in all other MRI markers ( p  < 0.017), suggesting it may be used as a surrogate marker of SVD damage across the cerebrum. Sample size estimates indicated that fewer patients would be required to detect treatment effects using DSEG θ compared to conventional MRI and DTI markers of SVD severity. DSEG θ is a powerful tool for characterising subtle brain change in SVD that has a negative impact on cognition and remains a significant predictor of cognitive change when other MRI markers of brain change are accounted for. DSEG provides an automatic segmentation of the whole cerebrum that is sensitive to a range of SVD related structural changes and successfully predicts cognitive change. Power analysis shows DSEG θ has potential as a monitoring tool in clinical trials. As such it may provide a marker of SVD severity from a single imaging modality (i.e. DTIs).

Genetic heterogeneity in families with non-epidermolytic palmar plantar keratosis

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

Spurr, N.K.; Kelshell, D.P.; Stevens, H.

1994-09-01

Following reports of linkage close to the keratin gene cluster in families with tylosis and the detection of mutations in the keratin 9 gene cosegregating in families with epidermolytic palmar plantar keratoderma (EPPK, and EPPK associated with breast and ovarian cancer), we have identified families with three phenotypically distinct forms of non-epidermolytic keratosis with either punctate, diffuse or focal keratoderma, one with diffuse lesions and one with punctate and malignancies. Initially we typed these families with 17q markers close to the keratin gene cluster; this included a dinucleotide repeat marker within the keratin 9 gene. Two point linkage analysis ofmore » the focal keratoderma family showed a positive lod score of 3.2 at a theta of 0 from the marker D17S855. The lod score for the diffuse family was -6.0 at a theta of 0.05 from the marker D17S776. The second focal keratoderma family showed a haplotype consistent with linkage to 17q close to the keratin gene cluster. A second keratin gene cluster has been mapped in humans on 12q, and we decided to test the unlinked diffuse and punctate keratoderma families with markers in that region. We used the markers: D12S87-D12S85-D12S368-D12S96-D12S90. Linkage analysis of the diffuse family gave a lod score of 3.1 at a theta of 0 from the marker D12S368. Currently studies are underway to look for mutations in specific keratin genes in the clusters on 17q and 12q that segregate with the observed phenotypes. The punctate keratoderma family gave lod scores of -3.9 at a theta of 0.55 with D17S855 and -6.0 at a theta of 0.05 with D12S90/D12S83. This would lead us to the conclusion that a separate susceptibility locus must exist for the punctate family associated with malignancy. Investigations of candidate regions are in progress.« less

Transgenerational epigenetics: Inheritance of global cytosine methylation and methylation-related epigenetic markers in the shrub Lavandula latifolia.

PubMed

Herrera, Carlos M; Alonso, Conchita; Medrano, Mónica; Pérez, Ricardo; Bazaga, Pilar

2018-04-01

The ecological and evolutionary significance of natural epigenetic variation (i.e., not based on DNA sequence variants) variation will depend critically on whether epigenetic states are transmitted from parents to offspring, but little is known on epigenetic inheritance in nonmodel plants. We present a quantitative analysis of transgenerational transmission of global DNA cytosine methylation (= proportion of all genomic cytosines that are methylated) and individual epigenetic markers (= methylation status of anonymous MSAP markers) in the shrub Lavandula latifolia. Methods based on parent-offspring correlations and parental variance component estimation were applied to epigenetic features of field-growing plants ('maternal parents') and greenhouse-grown progenies. Transmission of genetic markers (AFLP) was also assessed for reference. Maternal parents differed significantly in global DNA cytosine methylation (range = 21.7-36.7%). Greenhouse-grown maternal families differed significantly in global methylation, and their differences were significantly related to maternal origin. Methylation-sensitive amplified polymorphism (MSAP) markers exhibited significant transgenerational transmission, as denoted by significant maternal variance component of marker scores in greenhouse families and significant mother-offspring correlations of marker scores. Although transmission-related measurements for global methylation and MSAP markers were quantitatively lower than those for AFLP markers taken as reference, this study has revealed extensive transgenerational transmission of genome-wide global cytosine methylation and anonymous epigenetic markers in L. latifolia. Similarity of results for global cytosine methylation and epigenetic markers lends robustness to this conclusion, and stresses the value of considering both types of information in epigenetic studies of nonmodel plants. © 2018 Botanical Society of America.

Associations Among Plasma Stress Markers and Symptoms of Anxiety and Depression in Patients with Breast Cancer Following Surgery

PubMed Central

Ju, Hyun-Bin; Kang, Eun-Chan; Jeon, Dong-Wook; Kim, Tae-Hyun; Moon, Jung-Joon; Kim, Sung-Jin; Choi, Ji-Min; Jung, Do-Un

2018-01-01

Objective The objective of present study is to analyze the prevalence of depression and anxiety following breast cancer surgery and to assess the factors that affect postoperative psychological symptoms. Methods The Hamilton Rating Scale for Depression (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Body Image Scale (BIS), and Rosenberg Self Esteem Scale (RSES) were used to assess the psychological states of patients who had been diagnosed with and had undergone surgery for breast cancer. Blood concentrations of the stress markers adrenocorticotropic hormone, cortisol, arginine-vasopressin, and angiotensin-converting enzyme were measured. Pearson’s correlation analysis and multilinear regression analysis were used to analyse the data. Results At least mild depressive symptoms were noted in 50.5% of patients, while 42.4% of patients exhibited at least mild anxiety symptoms. HAM-D score was positively correlated with HAM-A (r=0.83, p<0.001) and BIS (r=0.29, p<0.001) scores and negatively correlated with RSES score (r=-0.41, p<0.001). HAM-A score was positively correlated with BIS score (r=0.32, p<0.001) and negatively correlated with RSES score (r=-0.27, p<0.001). There were no statistically significant associations between stress markers and depression/anxiety. Conclusion Patients with breast cancer frequently exhibit postoperative depression and anxiety, which are related to low levels of self-esteem and distorted body image. PMID:29475233

Genetic map of the spinocerebellar ataxia type 2 (SCA2) region on chromosome 12

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

Nechiporuk, A.; Frederick, T.; Pulst, S.M.

1994-09-01

The autosomal dominant ataxias (SCAs) are a clinically and genetically heterogeneous group of neurodegenerative diseases characterized by progressive ataxia. At least four gene loci have been identified: SCA1 on chromosome (CHR) 6, SCA2 on CHR12, Machado-Joseph disease on CHR14, and SCA families that are not linked to any of the above loci. In addition, the gene causing dentato-rubro-pallido-luysian atrophy has been identified as an expanded CAG repeat on CHR 12p. As a necessary step in identifying the gene for SCA2, we now identified closer flanking markers. To do this we ordered microsatellite markers in the now identified closer flanking markers.more » To do this we ordered microsatellite markers in the region and then determined pairwise and multipoint lod scores between the markers and SCA2 in three large pedigrees with SCA. The following order was established with odds > 1,000:1 using six non-SCA pedigrees: D12S101-7.1cM-D12S58-0cM-IGF1-3.6cM-D12S78-1.4cM-D12S317-3.7cM-D12S84-0cM-D12S105-7.2cM-D12S79-7.0cM-PLA2. Using this ordered set of markers we examined linkage to SCA2 in three pedigrees of Italian, Austrian and French-Canadian descent. Pairwise linkage analysis resulted in significant positive lod scores for all markers. The highest pairwise lod score was obtained with D12S84/D12S105 (Z{sub max}=7.98, theta{sub max}=0.05). To further define the location of SCA2, we performed multipoint linkage analysis using the genetic map established above. The highest location score was obtained between D12S317 and D12S84/D12S105. A location of SCA2 between these loci was favored with odds > 100:1. These data likely narrow the SCA2 candidate region to approximately 3.7 cM. The relatively large large number of markers tightly linked to SCA2 will facilitate the assignment of additional SCA pedigrees to CHR12, and will help in the presymptomatic diagnosis of individuals in families with proven linkage to CHR12.« less

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.

A dominant spinocerebellar ataxia gene (SCA5) in a family descendent from the paternal grandparents of President Lincoln maps to chromosome 11

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

Ranum, L.P.W.; Lundgren, J.K.; Schut, L.J.

1994-09-01

Four different genes that cause spinocerebellar ataxia (SCA1, SCA2, Machado Joseph`s Disease (MJD)/SCA3 and SCA4) have been mapped to chromosomes 6p, 12q, 14q, and 16q, respectively. We have examined and collected 170 individuals (56 affected) from a previously unreported 10 generation kindred (the Lincoln Family) with a dominant ataxia that is clinically and genetically distinct from those previously mapped. The family has two major branches from Indiana and Kentucky. Of historical interest is that both branches descend from the paternal grandparents of President Abraham Lincoln. While the ataxia in this kindred is disabling, the most striking clinical distinction from SCA1,more » SCA2 and MJD/SCA3 is that it is generally not life threatening. This clinical difference is explained by the absence of bulbar paralysis and lower motor neuron degeneration that causes respiratory muscle weakness. We have mapped the gene, SCA5, using microsatellite markers spaced at 20-40 cM intervals throughout the genome. After 75 markers, the first to demonstrate a lod score greater than 3.0 was D11S871 (Zmax=5.05). Four additional markers from the centromeric region of chromosome 11 also gave lod scores greater than 3. The highest lod scores were 12.3 for both D11S905 ({theta}=0.056) and D11S913 ({theta}=0.030). Multipoint linkage and haplotype analyses indicate the most likely location for SCA5 is within the 7 cM interval between GATA2A01 and D11S913. A statistical analysis of the age of onset of parent-offspring pairs within the family supports (p<0.0002) the presence of anticipation. Several dramatic examples of anticipation have been observed in which grandmothers have onsets 10-20 years later in life than their daughters who have onsets 10-20 years later than their children. Interestingly, all four of the juvenile onset cases are maternally inherited, suggesting a maternal bias in anticipation for SCA5 rather than a paternal bias as seen with SCA1.« less

Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts.

PubMed

Vimaleswaran, Karani S; Berry, Diane J; Lu, Chen; Tikkanen, Emmi; Pilz, Stefan; Hiraki, Linda T; Cooper, Jason D; Dastani, Zari; Li, Rui; Houston, Denise K; Wood, Andrew R; Michaëlsson, Karl; Vandenput, Liesbeth; Zgaga, Lina; Yerges-Armstrong, Laura M; McCarthy, Mark I; Dupuis, Josée; Kaakinen, Marika; Kleber, Marcus E; Jameson, Karen; Arden, Nigel; Raitakari, Olli; Viikari, Jorma; Lohman, Kurt K; Ferrucci, Luigi; Melhus, Håkan; Ingelsson, Erik; Byberg, Liisa; Lind, Lars; Lorentzon, Mattias; Salomaa, Veikko; Campbell, Harry; Dunlop, Malcolm; Mitchell, Braxton D; Herzig, Karl-Heinz; Pouta, Anneli; Hartikainen, Anna-Liisa; Streeten, Elizabeth A; Theodoratou, Evropi; Jula, Antti; Wareham, Nicholas J; Ohlsson, Claes; Frayling, Timothy M; Kritchevsky, Stephen B; Spector, Timothy D; Richards, J Brent; Lehtimäki, Terho; Ouwehand, Willem H; Kraft, Peter; Cooper, Cyrus; März, Winfried; Power, Chris; Loos, Ruth J F; Wang, Thomas J; Järvelin, Marjo-Riitta; Whittaker, John C; Hingorani, Aroon D; Hyppönen, Elina

2013-01-01

Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH)D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH)D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m(2) higher BMI was associated with 1.15% lower 25(OH)D (p = 6.52×10⁻²⁷). The BMI allele score was associated both with BMI (p = 6.30×10⁻⁶²) and 25(OH)D (-0.06% [95% CI -0.10 to -0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH)D (p≤8.07×10⁻⁵⁷ for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH)D concentrations (IV ratio: -4.2 [95% CI -7.1 to -1.3], p = 0.005). No association was seen for genetically instrumented 25(OH)D with BMI, a finding that was confirmed using data from the GIANT consortium (p≥0.57 for both vitamin D scores). On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH)D, while any effects of lower 25(OH)D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency.

PREDICT-PD: An online approach to prospectively identify risk indicators of Parkinson's disease.

PubMed

Noyce, Alastair J; R'Bibo, Lea; Peress, Luisa; Bestwick, Jonathan P; Adams-Carr, Kerala L; Mencacci, Niccolo E; Hawkes, Christopher H; Masters, Joseph M; Wood, Nicholas; Hardy, John; Giovannoni, Gavin; Lees, Andrew J; Schrag, Anette

2017-02-01

A number of early features can precede the diagnosis of Parkinson's disease (PD). To test an online, evidence-based algorithm to identify risk indicators of PD in the UK population. Participants aged 60 to 80 years without PD completed an online survey and keyboard-tapping task annually over 3 years, and underwent smell tests and genotyping for glucocerebrosidase (GBA) and leucine-rich repeat kinase 2 (LRRK2) mutations. Risk scores were calculated based on the results of a systematic review of risk factors and early features of PD, and individuals were grouped into higher (above 15th centile), medium, and lower risk groups (below 85th centile). Previously defined indicators of increased risk of PD ("intermediate markers"), including smell loss, rapid eye movement-sleep behavior disorder, and finger-tapping speed, and incident PD were used as outcomes. The correlation of risk scores with intermediate markers and movement of individuals between risk groups was assessed each year and prospectively. Exploratory Cox regression analyses with incident PD as the dependent variable were performed. A total of 1323 participants were recruited at baseline and >79% completed assessments each year. Annual risk scores were correlated with intermediate markers of PD each year and baseline scores were correlated with intermediate markers during follow-up (all P values < 0.001). Incident PD diagnoses during follow-up were significantly associated with baseline risk score (hazard ratio = 4.39, P = .045). GBA variants or G2019S LRRK2 mutations were found in 47 participants, and the predictive power for incident PD was improved by the addition of genetic variants to risk scores. The online PREDICT-PD algorithm is a unique and simple method to identify indicators of PD risk. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Evaluation of a prognostic scoring system based on the systemic inflammatory and nutritional status of patients with locally advanced non-small-cell lung cancer treated with chemoradiotherapy.

PubMed

Mitsuyoshi, Takamasa; Matsuo, Yukinori; Itou, Hitoshi; Shintani, Takashi; Iizuka, Yusuke; Kim, Young Hak; Mizowaki, Takashi

2018-01-01

Systemic inflammation and poor nutritional status have a negative effect on the outcomes of cancer. Here, we analyzed the effects of the pretreatment inflammatory and nutritional status on clinical outcomes of locally advanced non-small-cell lung cancer (NSCLC) patients treated with chemoradiotherapy. We retrospectively reviewed 89 patients with locally advanced NSCLC treated with chemoradiotherapy between July 2006 and June 2013. Serum C-reactive protein (CRP) was assessed as an inflammatory marker, and serum albumin, body mass index (BMI) and skeletal mass index were assessed as nutritional status markers. The relationships between these markers and overall survival (OS) were assessed. The median OS was 24.6 months [95% confidence interval (CI): 19.4-39.3 months]. During follow-up, 58 patients (65%) had disease recurrence and 52 patients (58%) died. In multivariate Cox hazard analysis, CRP levels and BMI approached but did not achieve a significant association with OS (P = 0.062 and 0.094, respectively). Recursive partitioning analysis identified three prognostic groups based on hazard similarity (CRP-BMI scores): 0 = CRP < 0.3 mg/dl, 1 = CRP ≥ 0.3 mg/dl and BMI ≥ 18.5 kg/m2, and 2 = CRP ≥ 0.3 mg/dl and BMI < 18.5 kg/m2. The CRP-BMI score was significantly associated with OS (P = 0.023). Patients with scores of 0, 1 and 2 had median OS of 39.3, 24.5 and 14.5 months, respectively, and the scores also predicted the probability of receiving salvage treatment after recurrence. The CRP-BMI score is thus a simple and useful prognostic marker of clinical outcome for patients with locally advanced NSCLC treated with chemoradiotherapy. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

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

PubMed

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

2015-08-18

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

Advances in plant gene-targeted and functional markers: a review

PubMed Central

2013-01-01

Public genomic databases have provided new directions for molecular marker development and initiated a shift in the types of PCR-based techniques commonly used in plant science. Alongside commonly used arbitrarily amplified DNA markers, other methods have been developed. Targeted fingerprinting marker techniques are based on the well-established practices of arbitrarily amplified DNA methods, but employ novel methodological innovations such as the incorporation of gene or promoter elements in the primers. These markers provide good reproducibility and increased resolution by the concurrent incidence of dominant and co-dominant bands. Despite their promising features, these semi-random markers suffer from possible problems of collision and non-homology analogous to those found with randomly generated fingerprints. Transposable elements, present in abundance in plant genomes, may also be used to generate fingerprints. These markers provide increased genomic coverage by utilizing specific targeted sites and produce bands that mostly seem to be homologous. The biggest drawback with most of these techniques is that prior genomic information about retrotransposons is needed for primer design, prohibiting universal applications. Another class of recently developed methods exploits length polymorphism present in arrays of multi-copy gene families such as cytochrome P450 and β-tubulin genes to provide cross-species amplification and transferability. A specific class of marker makes use of common features of plant resistance genes to generate bands linked to a given phenotype, or to reveal genetic diversity. Conserved DNA-based strategies have limited genome coverage and may fail to reveal genetic diversity, while resistance genes may be under specific evolutionary selection. Markers may also be generated from functional and/or transcribed regions of the genome using different gene-targeting approaches coupled with the use of RNA information. Such techniques have the potential to generate phenotypically linked functional markers, especially when fingerprints are generated from the transcribed or expressed region of the genome. It is to be expected that these recently developed techniques will generate larger datasets, but their shortcomings should also be acknowledged and carefully investigated. PMID:23406322

Using next generation sequencing for multiplexed trait-linked markers in wheat

USDA-ARS?s Scientific Manuscript database

With the advent of next generation sequencing (NGS) technologies, single nucleotide polymorphisms (SNPs) have become the major type of marker for genotyping in many crops. However, the availability of SNP markers for important traits of bread wheat (Triticum aestivum L.) that can be effectively used...

Detection of linkage between a quantitative trait and a marker locus by the lod score method: sample size and sampling considerations.

PubMed

Demenais, F; Lathrop, G M; Lalouel, J M

1988-07-01

A simulation study is here conducted to measure the power of the lod score method to detect linkage between a quantitative trait and a marker locus in various situations. The number of families necessary to detect such linkage with 80% power is assessed for different sets of parameters at the trait locus and different values of the recombination fraction. The effects of varying the mode of sampling families and the sibship size are also evaluated.

On computation of p-values in parametric linkage analysis.

PubMed

Kurbasic, Azra; Hössjer, Ola

2004-01-01

Parametric linkage analysis is usually used to find chromosomal regions linked to a disease (phenotype) that is described with a specific genetic model. This is done by investigating the relations between the disease and genetic markers, that is, well-characterized loci of known position with a clear Mendelian mode of inheritance. Assume we have found an interesting region on a chromosome that we suspect is linked to the disease. Then we want to test the hypothesis of no linkage versus the alternative one of linkage. As a measure we use the maximal lod score Z(max). It is well known that the maximal lod score has asymptotically a (2 ln 10)(-1) x (1/2 chi2(0) + 1/2 chi2(1)) distribution under the null hypothesis of no linkage when only one point (one marker) on the chromosome is studied. In this paper, we show, both by simulations and theoretical arguments, that the null hypothesis distribution of Zmax has no simple form when more than one marker is used (multipoint analysis). In fact, the distribution of Zmax depends on the number of families, their structure, the assumed genetic model, marker denseness, and marker informativity. This means that a constant critical limit of Zmax leads to tests associated with different significance levels. Because of the above-mentioned problems, from the statistical point of view the maximal lod score should be supplemented by a p-value when results are reported. Copyright (c) 2004 S. Karger AG, Basel.

Novel molecular markers differentiate Oncorhynchus mykiss (rainbow trout and steelhead) and the O. clarki (cutthroat trout) subspecies

USGS Publications Warehouse

Ostberg, C.O.; Rodriguez, R.J.

2002-01-01

A suite of 26 PCR-based markers was developed that differentiates rainbow (Oncorhynchus mykiss) and coastal cutthroat trout (O. clarki clarki). The markers also differentiated rainbow from other cutthroat trout subspecies (O. clarki), and several of the markers differentiated between cutthroat trout subspecies. This system has numerous positive attributes, including: nonlethal sampling, high species-specificity and products that are easily identified and scored using agarose gel electrophoresis. The methodology described for developing the markers can be applied to virtually any system in which numerous markers are desired for identifying or differentiating species or subspecies.

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.

Quantitative autistic trait measurements index background genetic risk for ASD in Hispanic families.

PubMed

Page, Joshua; Constantino, John Nicholas; Zambrana, Katherine; Martin, Eden; Tunc, Ilker; Zhang, Yi; Abbacchi, Anna; Messinger, Daniel

2016-01-01

Recent studies have indicated that quantitative autistic traits (QATs) of parents reflect inherited liabilities that may index background genetic risk for clinical autism spectrum disorder (ASD) in their offspring. Moreover, preferential mating for QATs has been observed as a potential factor in concentrating autistic liabilities in some families across generations. Heretofore, intergenerational studies of QATs have focused almost exclusively on Caucasian populations-the present study explored these phenomena in a well-characterized Hispanic population. The present study examined QAT scores in siblings and parents of 83 Hispanic probands meeting research diagnostic criteria for ASD, and 64 non-ASD controls, using the Social Responsiveness Scale-2 (SRS-2). Ancestry of the probands was characterized by genotype, using information from 541,929 single nucleotide polymorphic markers. In families of Hispanic children with an ASD diagnosis, the pattern of quantitative trait correlations observed between ASD-affected children and their first-degree relatives (ICCs on the order of 0.20), between unaffected first-degree relatives in ASD-affected families (sibling/mother ICC = 0.36; sibling/father ICC = 0.53), and between spouses (mother/father ICC = 0.48) were in keeping with the influence of transmitted background genetic risk and strong preferential mating for variation in quantitative autistic trait burden. Results from analysis of ancestry-informative genetic markers among probands in this sample were consistent with that from other Hispanic populations. Quantitative autistic traits represent measurable indices of inherited liability to ASD in Hispanic families. The accumulation of autistic traits occurs within generations, between spouses, and across generations, among Hispanic families affected by ASD. The occurrence of preferential mating for QATs-the magnitude of which may vary across cultures-constitutes a mechanism by which background genetic liability for ASD can accumulate in a given family in successive generations.

Comparison of Tear Osmolarity in Rheumatoid Arthritis Patients With and Without Secondary Sjogren Syndrome.

PubMed

Ng, Alex L K; Choy, Bonnie N K; Chan, Tommy C Y; Wong, Ian Y H; Lai, Jimmy S M; Mok, Mo Yin

2017-07-01

To compare tear osmolarity (TO) and other dry eye parameters in rheumatoid arthritis (RA) patients with or without secondary Sjogren syndrome (sSS). Consecutive patients with RA were divided into a sSS group and no-sSS group using conventional diagnostic criteria by rheumatologists using symptomatology, Schirmer test score, and anti-Ro or anti-La autoantibody status. The TO, Ocular Surface Disease Index, dry eye disease (DED) parameters [such as tear breakup time (TBUT) and corneal staining score] and the systemic inflammatory markers [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)] were compared. Correlation analyses between TO and the DED parameters and inflammatory markers were also performed. A total of 42 cases with mean age 54.8 ± 12.3 were included, with 12 patients (29%) having sSS and 30 (71%) without sSS. TO was increased in both groups (329 ± 20 and 319 ± 25 mOsm/L, respectively), but no statistically significant difference was found between the 2 groups (P = 0.126). RA with sSS had significantly shorter TBUT, higher corneal staining score, and ESR CRP levels (P < 0.05). TO did not correlate with the Schirmer test score, but had significant positive correlations with age, corneal staining score, ESR, and CRP levels, and a significant negative correlation with TBUT. TO was increased in RA patients with or without sSS. There was no significant correlation between TO and the Schirmer test score, and the physician could not use TO to diagnose sSS. However, TO correlated well with both DED parameters (TBUT and corneal staining score) and systemic inflammatory markers (ESR and CRP).

Tracking Drug-induced Changes in Receptor Post-internalization Trafficking by Colocalizational Analysis.

PubMed

Ong, Edmund; Cahill, Catherine

2015-07-03

The intracellular trafficking of receptors is a collection of complex and highly controlled processes. Receptor trafficking modulates signaling and overall cell responsiveness to ligands and is, itself, influenced by intra- and extracellular conditions, including ligand-induced signaling. Optimized for use with monolayer-plated cultured cells, but extendable to free-floating tissue slices, this protocol uses immunolabelling and colocalizational analysis to track changes in intracellular receptor trafficking following both chronic/prolonged and acute interventions, including exogenous drug treatment. After drug treatment, cells are double-immunolabelled for the receptor and for markers for the intracellular compartments of interest. Sequential confocal microscopy is then used to capture two-channel photomicrographs of individual cells, which are subjected to computerized colocalizational analysis to yield quantitative colocalization scores. These scores are normalized to permit pooling of independent replicates prior to statistical analysis. Representative photomicrographs may also be processed to generate illustrative figures. Here, we describe a powerful and flexible technique for quantitatively assessing induced receptor trafficking.

A next-generation marker genotyping platform (AmpSeq) in heterozygous crops: A case study for marker assisted selection in grapevine

USDA-ARS?s Scientific Manuscript database

Marker assisted selection (MAS) has become widely used in perennial crop breeding programs to accelerate and enhance cultivar development via selection during the juvenile phase and parental selection prior to crossing. Next generation sequencing (NGS) has been widely used for whole genome molecular...

A next-generation marker genotyping platform (AmpSeq) in heterozygous crops: a case study for marker assisted selection in grapevine

USDA-ARS?s Scientific Manuscript database

Marker assisted selection (MAS) is often employed in crop breeding programs to accelerate and enhance cultivar development, via selection during the juvenile phase and parental selection prior to crossing. Next generation sequencing (NGS) and its derivative technologies have been used for genome-wid...

Prognostic factors and scoring system for survival in colonic perforation.

PubMed

Komatsu, Shuhei; Shimomatsuya, Takumi; Nakajima, Masayuki; Amaya, Hirokazu; Kobuchi, Taketsune; Shiraishi, Susumu; Konishi, Sayuri; Ono, Susumu; Maruhashi, Kazuhiro

2005-01-01

No ideal and generally accepted prognostic factors and scoring systems exist to determine the prognosis of peritonitis associated with colonic perforation. This study was designed to investigate prognostic factors and evaluate the various scoring systems to allow identification of high-risk patients. Between 1996 and 2003, excluding iatrogenic and trauma cases, 26 consecutive patients underwent emergency operations for colorectal perforation and were selected for this retrospective study. Several clinical factors were analyzed as possible predictive factors, and APACHE II, SOFA, MPI, and MOF scores were calculated. The overall mortality was 26.9%. Compared with the survivors, non-survivors were found more frequently in Hinchey's stage III-IV, a low preoperative marker of pH, base excess (BE), and a low postoperative marker of white blood cell count, PaO2/FiO2 ratio, and renal output (24h). According to the logistic regression model, BE was a significant independent variable. Concerning the prognostic scoring systems, an APACHE II score of 19, a SOFA score of 8, an MPI score of 30, and an MOF score of 7 or more were significantly related to poor prognosis. Preoperative BE and postoperative white blood cell count were reliable prognostic factors and early classification using prognostic scoring systems at specific points in the disease process are useful to improve our understanding of the problems involved.

Standardized plant disease evaluations will enhance resistance gene discovery

USDA-ARS?s Scientific Manuscript database

Gene discovery and marker development using DNA-based tools require plant populations with well documented phenotypes. If dissimilar phenotype evaluation methods or data scoring techniques are employed with different crops, or at different labs for the same crops, then data mining for genetic marker...

Genome scan for linkage to asthma using a linkage disequilibrium-lod score test.

PubMed

Jiang, Y; Slager, S L; Huang, J

2001-01-01

We report a genome-wide linkage study of asthma on the German and Collaborative Study on the Genetics of Asthma (CSGA) data. Using a combined linkage and linkage disequilibrium test and the nonparametric linkage score, we identified 13 markers from the German data, 1 marker from the African American (CSGA) data, and 7 markers from the Caucasian (CSGA) data in which the p-values ranged between 0.0001 and 0.0100. From our analysis and taking into account previous published linkage studies of asthma, we suggest that three regions in chromosome 5 (around D5S418, D5S644, and D5S422), one region in chromosome 6 (around three neighboring markers D6S1281, D6S291, and D6S1019), one region in chromosome 11 (around D11S2362), and two regions in chromosome 12 (around D12S351 and D12S324) especially merit further investigation.

Bone health in cerebral palsy and introduction of a novel therapy

PubMed Central

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

2015-01-01

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

Integrated multigene expression panel to prognosticate patients with gastric cancer.

PubMed

Kanda, Mitsuro; Murotani, Kenta; Tanaka, Haruyoshi; Miwa, Takashi; Umeda, Shinichi; Tanaka, Chie; Kobayashi, Daisuke; Hayashi, Masamichi; Hattori, Norifumi; Suenaga, Masaya; Yamada, Suguru; Nakayama, Goro; Fujiwara, Michitaka; Kodera, Yasuhiro

2018-04-10

Most of the proposed individual markers had limited clinical utility due to the inherent biological and genetic heterogeneity of gastric cancer. We aimed to build a new molecular-based model to predict prognosis in patients with gastric cancer. A total of 200 patients who underwent gastric resection for gastric cancer were divided into learning and validation cohorts using a table of random numbers in a 1:1 ratio. In the learning cohort, mRNA expression levels of 15 molecular markers in gastric tissues were analyzed and concordance index (C-index) values of all single and combinations of the 15 candidate markers for overall survival were calculated. The multigene expression panel was designed according to C-index values and the subpopulation index. Expression scores were determined with weighting according to the coefficient of each constituent. The reproducibility of the panel was evaluated in the validation cohort. C-index values of the 15 single candidate markers ranged from 0.506-0.653. Among 32,767 combinations, the optimal and balanced expression panel comprised four constituents ( MAGED2, SYT8, BTG1 , and FAM46 ) and the C-index value was 0.793. Using this panel, patients were provisionally categorized with scores of 1-3, and clearly stratified into favorable, intermediate, and poor overall survival groups. In the validation cohort, both overall and disease-free survival rates decreased incrementally with increasing expression scores. Multivariate analysis revealed that the expression score was an independent prognostic factor for overall survival after curative gastrectomy. We developed an integrated multigene expression panel that simply and accurately stratified risk of patients with gastric cancer.

Correlation between the serum and tissue levels of oxidative stress markers and the extent of inflammation in acute appendicitis

PubMed Central

Dumlu, Ersin Gürkan; Tokaç, Mehmet; Bozkurt, Birkan; Yildirim, Murat Baki; Ergin, Merve; Yalçin, Abdussamed; Kiliç, Mehmet

2014-01-01

OBJECTIVES: To determine the serum and tissue levels of markers of impaired oxidative metabolism and correlate these levels with the histopathology and Alvarado score of acute appendicitis patients. METHOD: Sixty-five acute appendicitis patients (mean age, 31.4±12.06 years; male/female, 30/35) and 30 healthy control subjects were studied. The Alvarado score was recorded. Serum samples were obtained before surgery and 12 hours postoperatively to examine the total antioxidant status, total oxidant status, paraoxonase, stimulated paraoxonase, arylesterase, catalase, myeloperoxidase, ceruloplasmin, oxidative stress markers (advanced oxidized protein products and total thiol level) and ischemia-modified albumin. Surgical specimens were also evaluated. RESULTS: The diagnoses were acute appendicitis (n = 37), perforated appendicitis (n = 8), phlegmonous appendicitis (n = 12), perforated+phlegmonous appendicitis (n = 4), or no appendicitis (n = 4). The Alvarado score of the acute appendicitis group was significantly lower than that of the perforated+phlegmonous appendicitis group (p = 0.004). The serum total antioxidant status, total thiol level, advanced oxidized protein products, total oxidant status, catalase, arylesterase, and ischemia-modified albumin levels were significantly different between the acute appendicitis and control groups. There was no correlation between the pathological extent of acute appendicitis and the tissue levels of the markers; additionally, there was no correlation between the tissue and serum levels of any of the parameters. CONCLUSIONS: The imbalance of oxidant/antioxidant systems plays a role in the pathogenesis acute appendicitis. The Alvarado score can successfully predict the presence and extent of acute appendicitis. PMID:25518019

Reproducibility of a Standardized Actigraphy Scoring Algorithm for Sleep in a US Hispanic/Latino Population

PubMed Central

Patel, Sanjay R.; Weng, Jia; Rueschman, Michael; Dudley, Katherine A.; Loredo, Jose S.; Mossavar-Rahmani, Yasmin; Ramirez, Maricelle; Ramos, Alberto R.; Reid, Kathryn; Seiger, Ashley N.; Sotres-Alvarez, Daniela; Zee, Phyllis C.; Wang, Rui

2015-01-01

Study Objectives: While actigraphy is considered objective, the process of setting rest intervals to calculate sleep variables is subjective. We sought to evaluate the reproducibility of actigraphy-derived measures of sleep using a standardized algorithm for setting rest intervals. Design: Observational study. Setting: Community-based. Participants: A random sample of 50 adults aged 18–64 years free of severe sleep apnea participating in the Sueño sleep ancillary study to the Hispanic Community Health Study/Study of Latinos. Interventions: N/A. Measurements and Results: Participants underwent 7 days of continuous wrist actigraphy and completed daily sleep diaries. Studies were scored twice by each of two scorers. Rest intervals were set using a standardized hierarchical approach based on event marker, diary, light, and activity data. Sleep/wake status was then determined for each 30-sec epoch using a validated algorithm, and this was used to generate 11 variables: mean nightly sleep duration, nap duration, 24-h sleep duration, sleep latency, sleep maintenance efficiency, sleep fragmentation index, sleep onset time, sleep offset time, sleep midpoint time, standard deviation of sleep duration, and standard deviation of sleep midpoint. Intra-scorer intraclass correlation coefficients (ICCs) were high, ranging from 0.911 to 0.995 across all 11 variables. Similarly, inter-scorer ICCs were high, also ranging from 0.911 to 0.995, and mean inter-scorer differences were small. Bland-Altman plots did not reveal any systematic disagreement in scoring. Conclusions: With use of a standardized algorithm to set rest intervals, scoring of actigraphy for the purpose of generating a wide array of sleep variables is highly reproducible. Citation: Patel SR, Weng J, Rueschman M, Dudley KA, Loredo JS, Mossavar-Rahmani Y, Ramirez M, Ramos AR, Reid K, Seiger AN, Sotres-Alvarez D, Zee PC, Wang R. Reproducibility of a standardized actigraphy scoring algorithm for sleep in a US Hispanic/Latino population. SLEEP 2015;38(9):1497–1503. PMID:25845697

Evaluation of an ensemble of genetic models for prediction of a quantitative trait.

PubMed

Milton, Jacqueline N; Steinberg, Martin H; Sebastiani, Paola

2014-01-01

Many genetic markers have been shown to be associated with common quantitative traits in genome-wide association studies. Typically these associated genetic markers have small to modest effect sizes and individually they explain only a small amount of the variability of the phenotype. In order to build a genetic prediction model without fitting a multiple linear regression model with possibly hundreds of genetic markers as predictors, researchers often summarize the joint effect of risk alleles into a genetic score that is used as a covariate in the genetic prediction model. However, the prediction accuracy can be highly variable and selecting the optimal number of markers to be included in the genetic score is challenging. In this manuscript we present a strategy to build an ensemble of genetic prediction models from data and we show that the ensemble-based method makes the challenge of choosing the number of genetic markers more amenable. Using simulated data with varying heritability and number of genetic markers, we compare the predictive accuracy and inclusion of true positive and false positive markers of a single genetic prediction model and our proposed ensemble method. The results show that the ensemble of genetic models tends to include a larger number of genetic variants than a single genetic model and it is more likely to include all of the true genetic markers. This increased sensitivity is obtained at the price of a lower specificity that appears to minimally affect the predictive accuracy of the ensemble.

A Diagnostic Marker to Discriminate Childhood Apraxia of Speech From Speech Delay: I. Development and Description of the Pause Marker

PubMed Central

Strand, Edythe A.; Fourakis, Marios; Jakielski, Kathy J.; Hall, Sheryl D.; Karlsson, Heather B.; Mabie, Heather L.; McSweeny, Jane L.; Tilkens, Christie M.; Wilson, David L.

2017-01-01

Purpose The goal of this article (PM I) is to describe the rationale for and development of the Pause Marker (PM), a single-sign diagnostic marker proposed to discriminate early or persistent childhood apraxia of speech from speech delay. Method The authors describe and prioritize 7 criteria with which to evaluate the research and clinical utility of a diagnostic marker for childhood apraxia of speech, including evaluation of the present proposal. An overview is given of the Speech Disorders Classification System, including extensions completed in the same approximately 3-year period in which the PM was developed. Results The finalized Speech Disorders Classification System includes a nosology and cross-classification procedures for childhood and persistent speech disorders and motor speech disorders (Shriberg, Strand, & Mabie, 2017). A PM is developed that provides procedural and scoring information, and citations to papers and technical reports that include audio exemplars of the PM and reference data used to standardize PM scores are provided. Conclusions The PM described here is an acoustic-aided perceptual sign that quantifies one aspect of speech precision in the linguistic domain of phrasing. This diagnostic marker can be used to discriminate early or persistent childhood apraxia of speech from speech delay. PMID:28384779

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

DNA Barcode Sequence Identification Incorporating Taxonomic Hierarchy and within Taxon Variability

PubMed Central

Little, Damon P.

2011-01-01

For DNA barcoding to succeed as a scientific endeavor an accurate and expeditious query sequence identification method is needed. Although a global multiple–sequence alignment can be generated for some barcoding markers (e.g. COI, rbcL), not all barcoding markers are as structurally conserved (e.g. matK). Thus, algorithms that depend on global multiple–sequence alignments are not universally applicable. Some sequence identification methods that use local pairwise alignments (e.g. BLAST) are unable to accurately differentiate between highly similar sequences and are not designed to cope with hierarchic phylogenetic relationships or within taxon variability. Here, I present a novel alignment–free sequence identification algorithm–BRONX–that accounts for observed within taxon variability and hierarchic relationships among taxa. BRONX identifies short variable segments and corresponding invariant flanking regions in reference sequences. These flanking regions are used to score variable regions in the query sequence without the production of a global multiple–sequence alignment. By incorporating observed within taxon variability into the scoring procedure, misidentifications arising from shared alleles/haplotypes are minimized. An explicit treatment of more inclusive terminals allows for separate identifications to be made for each taxonomic level and/or for user–defined terminals. BRONX performs better than all other methods when there is imperfect overlap between query and reference sequences (e.g. mini–barcode queries against a full–length barcode database). BRONX consistently produced better identifications at the genus–level for all query types. PMID:21857897

Initial experience of using an iron-containing fiducial marker for radiotherapy of prostate cancer: Advantages in the visualization of markers in Computed Tomography and Magnetic Resonance Imaging

NASA Astrophysics Data System (ADS)

Tanaka, Osamu; Iida, Takayoshi; Komeda, Hisao; Tamaki, Masayoshi; Seike, Kensaku; Kato, Daiki; Yokoyama, Takamasa; Hirose, Shigeki; Kawaguchi, Daisuke

2016-12-01

Visualization of markers is critical for imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI). However, the size of the marker varies according to the imaging technique. While a large-sized marker is more useful for visualization in MRI, it results in artifacts on CT and causes substantial pain on administration. In contrast, a small-sized marker reduces the artifacts on CT but hampers MRI detection. Herein, we report a new ironcontaining marker and compare its utility with that of non-iron-containing markers. Five patients underwent CT/MRI fusion-based intensity-modulated radiotherapy, and the markers were placed by urologists. A Gold Anchor™ (GA; diameter, 0.28 mm; length, 10 mm) was placed using a 22G needle on the right side of the prostate. A VISICOIL™ (VIS; diameter, 0.35 mm; length, 10 mm) was placed using a 19G needle on the left side. MRI was performed using T2*-weighted imaging. Three observers evaluated and scored the visual qualities of the acquired images. The mean score of visualization was almost identical between the GA and VIS in radiography and cone-beam CT (Novalis Tx). The artifacts in planning CT were slightly larger using the GA than using the VIS. The visualization of the marker on MRI using the GA was superior to that using the VIS. In conclusion, the visualization quality of radiography, conebeam CT, and planning CT was roughly equal between the GA and VIS. However, the GA was more strongly visualized than was the VIS on MRI due to iron containing.

Multiple-clone infections of Plasmodium vivax: definition of a panel of markers for molecular epidemiology.

PubMed

de Souza, Aracele M; de Araújo, Flávia C F; Fontes, Cor J F; Carvalho, Luzia H; de Brito, Cristiana F A; de Sousa, Taís N

2015-08-25

Plasmodium vivax infections commonly contain multiple genetically distinct parasite clones. The detection of multiple-clone infections depends on several factors, such as the accuracy of the genotyping method, and the type and number of the molecular markers analysed. Characterizing the multiplicity of infection has broad implications that range from population genetic studies of the parasite to malaria treatment and control. This study compared and evaluated the efficiency of neutral and non-neutral markers that are widely used in studies of molecular epidemiology to detect the multiplicity of P. vivax infection. The performance of six markers was evaluated using 11 mixtures of DNA with well-defined proportions of two different parasite genotypes for each marker. These mixtures were generated by mixing cloned PCR products or patient-derived genomic DNA. In addition, 51 samples of natural infections from the Brazil were genotyped for all markers. The PCR-capillary electrophoresis-based method was used to permit direct comparisons among the markers. The criteria for differentiating minor peaks from artifacts were also evaluated. The analysis of DNA mixtures showed that the tandem repeat MN21 and the polymorphic blocks 2 (msp1B2) and 10 (msp1B10) of merozoite surface protein-1 allowed for the estimation of the expected ratio of both alleles in the majority of preparations. Nevertheless, msp1B2 was not able to detect the majority of multiple-clone infections in field samples; it identified only 6 % of these infections. The merozoite surface protein-3 alpha and microsatellites (PvMS6 and PvMS7) did not accurately estimate the relative clonal proportions in artificial mixtures, but the microsatellites performed well in detecting natural multiple-clone infections. Notably, the use of a less stringent criterion to score rare alleles significantly increased the sensitivity of the detection of multi-clonal infections. Depending on the type of marker used, a considerable amplification bias was observed, which may have serious implications for the characterization of the complexity of a P. vivax infection. Based on the performance of markers in artificial mixtures of DNA and natural infections, a minimum panel of four genetic markers (PvMS6, PvMS7, MN21, and msp1B10) was defined, and these markers are highly informative regarding the genetic variability of P. vivax populations.

Physicochemical assessment criteria for high-voltage pulse capacitors

NASA Astrophysics Data System (ADS)

Darian, L. A.; Lam, L. Kh.

2016-12-01

In the paper, the applicability of decomposition products of internal insulation of high-voltage pulse capacitors is considered (aging is the reason for decomposition products of internal insulation). Decomposition products of internal insulation of high-voltage pulse capacitors can be used to evaluate their quality when in operation and in service. There have been three generations of markers of aging of insulation as in the case with power transformers. The area of applicability of markers of aging of insulation for power transformers has been studied and the area can be extended to high-voltage pulse capacitors. The research reveals that there is a correlation between the components and quantities of markers of aging of the first generation (gaseous decomposition products of insulation) dissolved in insulating liquid and the remaining life of high-voltage pulse capacitors. The application of markers of aging to evaluate the remaining service life of high-voltage pulse capacitor is a promising direction of research, because the design of high-voltage pulse capacitors keeps stability of markers of aging of insulation in high-voltage pulse capacitors. It is necessary to continue gathering statistical data concerning development of markers of aging of the first generation. One should also carry out research aimed at estimation of the remaining life of capacitors using markers of the second and the third generation.

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.

Autosomal dominant cerebellar ataxia with retinal degeneration (ADCA II): clinical and neuropathological findings in two pedigrees and genetic linkage to 3p12-p21.1.

PubMed

Jöbsis, G J; Weber, J W; Barth, P G; Keizers, H; Baas, F; van Schooneveld, M J; van Hilten, J J; Troost, D; Geesink, H H; Bolhuis, P A

1997-04-01

To investigate relations between clinical and neuropathological features and age of onset, presence of anticipation, and genetic linkage in autosomal dominant cerebellar ataxia type II (ADCA II). The natural history of ADCA II was studied on the basis of clinical and neuropathological findings in two pedigrees and genetic linkage studies were carried out with polymorphic DNA markers in the largest, four generation, pedigree. Ataxia was constant in all age groups. Retinal degeneration with early extinction of the electroretinogram constituted an important component in juvenile and early adult (< 25 years) onset but was variable in late adult presentation. Neuromuscular involvement due to spinal anterior horn disease was an important contributing factor to illness in juvenile cases. Postmortem findings in four patients confirm the general neurodegenerative nature of the disease, which includes prominent spinal anterior horn involvement and widespread involvement of grey and white matter. Genetic linkage was found with markers to chromosome 3p12-p21.1 (maximum pairwise lod score 4.42 at D3S1285). The sequence of clinical involvement seems related to age at onset. Retinal degeneration is variable in late onset patients and neuromuscular features are important in patients with early onset. Strong anticipation was found in subsequent generations. Linkage of ADCA II to chromosome 3p12-p21.1 is confirmed.

Revised Framingham Stroke Risk Score, Nontraditional Risk Markers, and Incident Stroke in a Multiethnic Cohort.

PubMed

Flueckiger, Peter; Longstreth, Will; Herrington, David; Yeboah, Joseph

2018-02-01

Limited data exist on the performance of the revised Framingham Stroke Risk Score (R-FSRS) and the R-FSRS in conjunction with nontraditional risk markers. We compared the R-FSRS, original FSRS, and the Pooled Cohort Equation for stroke prediction and assessed the improvement in discrimination by nontraditional risk markers. Six thousand seven hundred twelve of 6814 participants of the MESA (Multi-Ethnic Study of Atherosclerosis) were included. Cox proportional hazard, area under the curve, net reclassification improvement, and integrated discrimination increment analysis were used to assess and compare each stroke prediction risk score. Stroke was defined as fatal/nonfatal strokes (hemorrhagic or ischemic). After mean follow-up of 10.7 years, 231 of 6712 (3.4%) strokes were adjudicated (2.7% ischemic strokes). Mean stroke risks using the R-FSRS, original FSRS, and Pooled Cohort Equation were 4.7%, 5.9%, and 13.5%. The R-FSRS had the best calibration (Hosmer-Lemeshow goodness-of-fit, χ 2 =6.55; P =0.59). All risk scores were predictive of incident stroke. C statistics of R-FSRS (0.716) was similar to Pooled Cohort Equation (0.716), but significantly higher than the original FSRS (0.653; P =0.01 for comparison with R-FSRS). Adding nontraditional risk markers individually to the R-FSRS did not improve discrimination of the R-FSRS in the area under the curve analysis, but did improve category-less net reclassification improvement and integrated discrimination increment for incident stroke. The addition of coronary artery calcium to R-FSRS produced the highest category-less net reclassification improvement (0.36) and integrated discrimination increment (0.0027). Similar results were obtained when ischemic strokes were used as the outcome. The R-FSRS downgraded stroke risk but had better calibration and discriminative ability for incident stroke compared with the original FSRS. Nontraditional risk markers modestly improved the discriminative ability of the R-FSRS, with coronary artery calcium performing the best. © 2018 American Heart Association, Inc.

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

PubMed

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

2016-09-01

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

An Objective Screening Method for Major Depressive Disorder Using Logistic Regression Analysis of Heart Rate Variability Data Obtained in a Mental Task Paradigm.

PubMed

Sun, Guanghao; Shinba, Toshikazu; Kirimoto, Tetsuo; Matsui, Takemi

2016-01-01

Heart rate variability (HRV) has been intensively studied as a promising biological marker of major depressive disorder (MDD). Our previous study confirmed that autonomic activity and reactivity in depression revealed by HRV during rest and mental task (MT) conditions can be used as diagnostic measures and in clinical evaluation. In this study, logistic regression analysis (LRA) was utilized for the classification and prediction of MDD based on HRV data obtained in an MT paradigm. Power spectral analysis of HRV on R-R intervals before, during, and after an MT (random number generation) was performed in 44 drug-naïve patients with MDD and 47 healthy control subjects at Department of Psychiatry in Shizuoka Saiseikai General Hospital. Logit scores of LRA determined by HRV indices and heart rates discriminated patients with MDD from healthy subjects. The high frequency (HF) component of HRV and the ratio of the low frequency (LF) component to the HF component (LF/HF) correspond to parasympathetic and sympathovagal balance, respectively. The LRA achieved a sensitivity and specificity of 80.0 and 79.0%, respectively, at an optimum cutoff logit score (0.28). Misclassifications occurred only when the logit score was close to the cutoff score. Logit scores also correlated significantly with subjective self-rating depression scale scores ( p  < 0.05). HRV indices recorded during a MT may be an objective tool for screening patients with MDD in psychiatric practice. The proposed method appears promising for not only objective and rapid MDD screening but also evaluation of its severity.

Fecal Markers of Environmental Enteropathy and Subsequent Growth in Bangladeshi Children.

PubMed

Arndt, Michael B; Richardson, Barbra A; Ahmed, Tahmeed; Mahfuz, Mustafa; Haque, Rashidul; John-Stewart, Grace C; Denno, Donna M; Petri, William A; Kosek, Margaret; Walson, Judd L

2016-09-07

Environmental enteropathy (EE), a subclinical intestinal disorder characterized by mucosal inflammation, reduced barrier integrity, and malabsorption, appears to be associated with increased risk of stunting in children in low- and middle-income countries. Fecal biomarkers indicative of EE (neopterin [NEO], myeloperoxidase [MPO], and alpha-1-antitrypsin [AAT]) have been negatively associated with 6-month linear growth. Associations between fecal markers (NEO, MPO, and AAT) and short-term linear growth were examined in a birth cohort of 246 children in Bangladesh. Marker concentrations were categorized in stool samples based on their distribution (< first quartile, interquartile range, > third quartile), and a 10-point composite EE score was calculated. Piecewise linear mixed-effects models were used to examine the association between markers measured quarterly (in months 3-21, 3-9, and 12-21) and 3-month change in length-for-age z-score (ΔLAZ). Children with high MPO levels at quarterly time points lost significantly more LAZ per 3-month period during the second year of life than those with low MPO (ΔLAZ = -0.100; 95% confidence interval = -0.167 to -0.032). AAT and NEO were not associated with growth; however, composite EE score was negatively associated with subsequent 3-month growth. In this cohort of children from an urban setting in Bangladesh, elevated MPO levels, but not NEO or AAT levels, were associated with decreases in short-term linear growth during the second year of life, supporting previous data suggesting the relevance of MPO as a marker of EE. © The American Society of Tropical Medicine and Hygiene.

Plasma cell-free DNA and qSOFA score predict 7-day mortality in 481 emergency department bacteraemia patients.

PubMed

Rannikko, Juha; Seiskari, Tapio; Huttunen, Reetta; Tarkiainen, Iina; Jylhävä, Juulia; Hurme, Mikko; Syrjänen, Jaana; Aittoniemi, Janne

2018-04-24

A few studies have shown that both quick Sequential Organ Failure Assessment (qSOFA) score and cell-free DNA (cfDNA) have potential use as a prognostic marker in patients with infection. We studied these two markers alone and in combination to identify those emergency department (ED) patients with the highest risk of death. Plasma cfDNA level was studied on days 0 to 4 after admittance to the ED from 481 culture-positive bloodstream infection cases. The qSOFA score was evaluated retrospectively according to Sepsis-3 definitions. The primary outcome was death by day 7. CfDNA on day 0 was significantly higher in non-survivors than in survivors (2.02 μg/ml vs. 1.35 μg/ml, p<0.001). CfDNA level was high (>1.69 μg/ml) in 134 (28%) out of 481 cases and the qSOFA score was ≥2 in 128 (28%) out of 458 cases. High cfDNA and qSOFA score ≥2 had 70% and 77% sensitivity and 76% and 76% specificity in predicting death by day 7, respectively. High cfDNA alone had odds ratio (OR) of 7.7 (95% CI 3.9-15.3) and qSOFA score ≥2 OR of 11.6 (5.5-24.3), but their combination had OR of 20.3 (10.0-41.4) in predicting death by day 7 when compared with those with low cfDNA and qSOFA score <2. Among the five cases with the highest cfDNA levels, there were three patients with severe disseminated intravascular coagulation. CfDNA and qSOFA score can be used independently to identify those bacteraemia patients at high risk of death, and combining these two markers gives additional advantage. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Buprenorphine Alters Inflammatory and Oxidative Stress Molecular Markers in Arthritis

PubMed Central

Hitchon, Carol

2017-01-01

Buprenorphine is recommended for use as an analgesic in animal models including in murine models of collagen-induced arthritis (CIA). However, the effect of buprenorphine on the expression of disease-associated biomarkers is not well defined. We examined the effect of buprenorphine administration on disease progression and the expression of inflammatory and oxidative stress markers, in a murine model of CIA. Buprenorphine administration altered the expression of cytokines, IFN-γ, IL-6, and MMP-3, and oxidative markers, for example, iNOS, superoxide dismutase (SOD1), and catalase (CAT), in the CIA mice. As buprenorphine is an analgesic, we further monitored the association of expression of these biomarkers with pain scores in a human cohort of early rheumatoid arthritis (RA). Serum MMP-3 levels and blood mRNA expression of antioxidants sod1 and cat correlated with pain scores in the RA cohort. We have demonstrated that administration of buprenorphine alters the expression of inflammatory and oxidative stress-related molecular markers in a murine model of CIA. This caveat needs to be considered in animal experiments using buprenorphine as an analgesic, as it can be a confounding factor in murine studies used for prediction of response to therapy. Furthermore, the antioxidant enzymes that showed an association with pain scores in the human cohort may be explored as biomarkers for pain in future studies. PMID:28572711

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

Campbell, W; Miften, M; Jones, B

Purpose: Pancreatic SBRT relies on extremely accurate delivery of ablative radiation doses to the target, and intra-fractional tracking of fiducial markers can facilitate improvements in dose delivery. However, this requires algorithms that are able to find fiducial markers with high speed and accuracy. The purpose of this study was to develop a novel marker tracking algorithm that is robust against many of the common errors seen with traditional template matching techniques. Methods: Using CBCT projection images, a method was developed to create detailed template images of fiducial marker clusters without prior knowledge of the number of markers, their positions, ormore » their orientations. Briefly, the method (i) enhances markers in projection images, (ii) stabilizes the cluster’s position, (iii) reconstructs the cluster in 3D, and (iv) precomputes a set of static template images dependent on gantry angle. Furthermore, breathing data were used to produce 4D reconstructions of clusters, yielding dynamic template images dependent on gantry angle and breathing amplitude. To test these two approaches, static and dynamic templates were used to track the motion of marker clusters in more than 66,000 projection images from 75 CBCT scans of 15 pancreatic SBRT patients. Results: For both static and dynamic templates, the new technique was able to locate marker clusters present in projection images 100% of the time. The algorithm was also able to correctly locate markers in several instances where only some of the markers were visible due to insufficient field-of-view. In cases where clusters exhibited deformation and/or rotation during breathing, dynamic templates resulted in cross-correlation scores up to 70% higher than static templates. Conclusion: Patient-specific templates provided complete tracking of fiducial marker clusters in CBCT scans, and dynamic templates helped to provide higher cross-correlation scores for deforming/rotating clusters. This novel algorithm provides an extremely accurate method to detect fiducial markers during treatment. Research funding provided by Varian Medical Systems to Miften and Jones.« less

QTL mapping for fruit quality in Citrus using DArTseq markers.

PubMed

Curtolo, Maiara; Cristofani-Yaly, Mariângela; Gazaffi, Rodrigo; Takita, Marco Aurélio; Figueira, Antonio; Machado, Marcos Antonio

2017-04-12

Citrus breeding programs have many limitations associated with the species biology and physiology, requiring the incorporation of new biotechnological tools to provide new breeding possibilities. Diversity Arrays Technology (DArT) markers, combined with next-generation sequencing, have wide applicability in the construction of high-resolution genetic maps and in quantitative trait locus (QTL) mapping. This study aimed to construct an integrated genetic map using full-sib progeny derived from Murcott tangor and Pera sweet orange and DArTseq™ molecular markers and to perform QTL mapping of twelve fruit quality traits. A controlled Murcott x Pera crossing was conducted at the Citrus Germplasm Repository at the Sylvio Moreira Citrus Centre of the Agronomic Institute (IAC) located in Cordeirópolis, SP, in 1997. In 2012, 278 F 1 individuals out of a family of 312 confirmed hybrid individuals were analyzed for fruit traits and genotyped using the DArTseq markers. Using OneMap software to obtain the integrated genetic map, we considered only the DArT loci that showed no segregation deviation. The likelihood ratio and the genomic information from the available Citrus sinensis L. Osbeck genome were used to determine the linkage groups (LGs). The resulting integrated map contained 661 markers in 13 LGs, with a genomic coverage of 2,774 cM and a mean density of 0.23 markers/cM. The groups were assigned to the nine Citrus haploid chromosomes; however, some of the chromosomes were represented by two LGs due the lack of information for a single integration, as in cases where markers segregated in a 3:1 fashion. A total of 19 QTLs were identified through composite interval mapping (CIM) of the 12 analyzed fruit characteristics: fruit diameter (cm), height (cm), height/diameter ratio, weight (g), rind thickness (cm), segments per fruit, total soluble solids (TSS, %), total titratable acidity (TTA, %), juice content (%), number of seeds, TSS/TTA ratio and number of fruits per box. The genomic sequence (pseudochromosomes) of C. sinensis was compared to the genetic map, and synteny was clearly identified. Further analysis of the map regions with the highest LOD scores enabled the identification of putative genes that could be associated with the fruit quality characteristics. An integrated linkage map of Murcott tangor and Pera sweet orange using DArTseq™ molecular markers was established and it was useful to perform QTL mapping of twelve fruit quality traits. The next generation sequences data allowed the comparison between the linkage map and the genomic sequence (pseudochromosomes) of C. sinensis and the identification of genes that may be responsible for phenotypic traits in Citrus. The obtained linkage map was used to assign sequences that had not been previously assigned to a position in the reference genome.

Screening for type 2 diabetes and prediabetes in obese youth: evaluating alternate markers of glycemia - 1,5-anhydroglucitol, fructosamine, and glycated albumin.

PubMed

Chan, Christine L; Pyle, Laura; Kelsey, Megan; Newnes, Lindsey; Zeitler, Philip S; Nadeau, Kristen J

2016-05-01

Hemoglobin A1c (HbA1c) is increasingly performed over the oral glucose tolerance test (OGTT) as the initial screening test for type 2 diabetes in youth. However, the optimal strategy for identifying type 2 diabetes in youth remains controversial. Alternate glycemic markers have been proposed as potentially useful tools for diabetes screening. We examined the relationships among fructosamine (FA), glycated albumin (GA), and 1,5-anhydroglucitol (1,5-AG) with traditional screening tests, HbA1c and OGTT. Youth 10-18 yrs, BMI ≥85th‰, and HbA1c <7.5% had a single visit with measurement of HbA1c, 1,5-AG, FA, GA, and a standard OGTT. Distributions of FA, GA, and 1,5-AG by HbA1c and 2-hour glucose (2hG) categories were compared. Receiver operating characteristic (ROC)-curves were generated to determine the cut points at which alternate markers maximized sensitivity and specificity for predicting prediabetes and diabetes. One hundred and seventeen, 62% female, 59% Hispanic, 22% White, 17% black, median 14.1 yr, and body mass index (BMI) z-score 2.3 participated. Median values of each alternate marker differed significantly between prediabetes and diabetes HbA1c and 2hG categories (p < 0.017). Only GA medians differed (p = 0.006) between normal and prediabetes HbA1c. Area under the receiver operating characteristic curves (ROC-AUCs) for alternate markers as predictors of prediabetes (0.5-0.66) were low; however, alternate marker ROC-AUCs for identifying diabetes (0.82-0.98) were excellent. Although the alternate markers were poor predictors of prediabetes, they all performed well predicting diabetes by 2hG and HbA1c. Whereas the usefulness of these markers for identifying prediabetes is limited, they may be useful in certain scenarios as second line screening tools for diabetes in overweight/obese youth. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prenatal Sonographic Predictors of Neonatal Coarctation of the Aorta.

PubMed

Anuwutnavin, Sanitra; Satou, Gary; Chang, Ruey-Kang; DeVore, Greggory R; Abuel, Ashley; Sklansky, Mark

2016-11-01

To identify practical prenatal sonographic markers for the postnatal diagnosis of coarctation of the aorta. We reviewed the fetal echocardiograms and postnatal outcomes of fetal cases of suspected coarctation of the aorta seen at a single institution between 2010 and 2014. True- and false-positive cases were compared. Logistic regression analysis was used to determine echocardiographic predictors of coarctation of the aorta. Optimal cutoffs for these markers and a multivariable threshold scoring system were derived to discriminate fetuses with coarctation of the aorta from those without coarctation of the aorta. Among 35 patients with prenatal suspicion of coarctation of the aorta, the diagnosis was confirmed postnatally in 9 neonates (25.7% true-positive rate). Significant predictors identified from multivariate analysis were as follows: Z score for the ascending aorta diameter of -2 or less (P = < .001), Z score for the mitral valve annulus of -2 or less (P= .033), Zscore for the transverse aortic arch diameter of -2 or less (P= .028), and abnormal aortic valve morphologic features (P= .026). Among all variables studied, the ascending aortic Z score had the highest sensitivity (78%) and specificity (92%) for detection of coarctation of the aorta. A multivariable threshold scoring system identified fetuses with coarctation of the aorta with still greater sensitivity (89%) and only mildly decreased specificity (88%). The finding of a diminutive ascending aorta represents a powerful and practical prenatal predictor of neonatal coarctation of the aorta. A multivariable scoring system, including dimensions of the ascending and transverse aortas, mitral valve annulus, and morphologic features of the aortic valve, provides excellent sensitivity and specificity. The use of these practical sonographic markers may improve prenatal detection of coarctation of the aorta. © 2016 by the American Institute of Ultrasound in Medicine.

The BRICS (Bronchiectasis Radiologically Indexed CT Score): A Multicenter Study Score for Use in Idiopathic and Postinfective Bronchiectasis.

PubMed

Bedi, Pallavi; Chalmers, James D; Goeminne, Pieter C; Mai, Cindy; Saravanamuthu, Pira; Velu, Prasad Palani; Cartlidge, Manjit K; Loebinger, Michael R; Jacob, Joe; Kamal, Faisal; Schembri, Nicola; Aliberti, Stefano; Hill, Uta; Harrison, Mike; Johnson, Christopher; Screaton, Nicholas; Haworth, Charles; Polverino, Eva; Rosales, Edmundo; Torres, Antoni; Benegas, Michael N; Rossi, Adriano G; Patel, Dilip; Hill, Adam T

2018-05-01

The goal of this study was to develop a simplified radiological score that could assess clinical disease severity in bronchiectasis. The Bronchiectasis Radiologically Indexed CT Score (BRICS) was devised based on a multivariable analysis of the Bhalla score and its ability in predicting clinical parameters of severity. The score was then externally validated in six centers in 302 patients. A total of 184 high-resolution CT scans were scored for the validation cohort. In a multiple logistic regression model, disease severity markers significantly associated with the Bhalla score were percent predicted FEV 1 , sputum purulence, and exacerbations requiring hospital admission. Components of the Bhalla score that were significantly associated with the disease severity markers were bronchial dilatation and number of bronchopulmonary segments with emphysema. The BRICS was developed with these two parameters. The receiver operating-characteristic curve values for BRICS in the derivation cohort were 0.79 for percent predicted FEV 1 , 0.71 for sputum purulence, and 0.75 for hospital admissions per year; these values were 0.81, 0.70, and 0.70, respectively, in the validation cohort. Sputum free neutrophil elastase activity was significantly elevated in the group with emphysema on CT imaging. A simplified CT scoring system can be used as an adjunct to clinical parameters to predict disease severity in patients with idiopathic and postinfective bronchiectasis. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Circulating Markers of Vascular Injury and Angiogenesis in ANCA-Associated Vasculitis

PubMed Central

Monach, Paul A; Tomasson, Gunnar; Specks, Ulrich; Stone, John H; Cuthbertson, David; Krischer, Jeffrey; Ding, Linna; Fervenza, Fernando C; Fessler, Barri J; Hoffman, Gary S; Ikle, David; Kallenberg, Cees GM; Langford, Carol A; Mueller, Mark; Seo, Philip; St.Clair, E William; Spiera, Robert; Tchao, Nadia; Ytterberg, Steven R; Gu, Yi-Zhong; Snyder, Ronald D; Merkel, Peter A

2011-01-01

Objective To identify biomarkers that distinguish between active ANCA-associated vasculitis (AAV) and remission in a manner superior or complementary to established markers of systemic inflammation. Methods Markers of vascular injury and angiogenesis were measured before and after treatment in a large clinical trial in AAV. 163 subjects enrolled in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial were studied. Serum levels of E-selectin, ICAM-3, MMP1, MMP3, MMP9, P-selectin, thrombomodulin, and VEGF were measured at study screening (time of active disease) and at month 6. ESR and CRP levels had been measured at the time of the clinical visit. The primary outcome was the difference in marker level between screening and month 6 among patients in remission (BVAS/WG score of 0) at month 6. Results All subjects had severe active vasculitis (mean BVAS/WG score 8.6 +/− 3.2 SD) at screening. Among the 123 subjects clinically in remission at month 6, levels of all markers except E-selectin showed significant declines. MMP3 levels were also higher among the 23 subjects with active disease at month 6 than among the 123 subjects in remission. MMP3 levels correlated weakly with ESR and CRP. Conclusion Many markers of vascular injury and angiogenesis are elevated in severe active AAV and decline with treatment, but MMP3 appears to distinguish active AAV from remission better than the other markers studied. Further study of MMP3 is warranted to determine its clinical utility in combination with conventional markers of inflammation and ANCA titers. PMID:21953143

Mental health symptoms as prognostic risk markers of all-cause and psychiatric sickness absence in office workers.

PubMed

Roelen, Corné A M; Hoedeman, Rob; van Rhenen, Willem; Groothoff, Johan W; van der Klink, Jac J L; Bültmann, Ute

2014-02-01

To investigate mental health symptoms as prognostic risk markers of all-cause and psychiatric sickness absence (SA). Mental health symptoms were measured in 1137 office workers with the Four-Dimensional Symptom Questionnaire (4DSQ), including scales for distress, depression, anxiety and somatization. The total number of SA days was accumulated prospectively on the individual level and high SA was defined as ≥30 SA days during 1-year follow-up. Psychiatric SA was also tallied on the individual level during 1-year follow-up. Baseline 4DSQ scores were associated with high all-cause SA and psychiatric SA by logistic regression analysis. The Hosmer-Lemeshow test and calibration slope were used to assess the accuracy of predictions by 4DSQ scores. The ability of 4DSQ scores to discriminate high-risk from low-risk employees was estimated by the area under the receiver operating characteristic curve. Six hundred thirty-three office workers (56%) participated in the study. All 4DSQ scales were prospectively associated with high all-cause SA and with psychiatric SA. Distress and somatization scores showed acceptable calibration, but failed to discriminate between office workers with and without high all-cause SA. The distress scale did show adequate calibration (calibration slope = 0.95) and discrimination (area under the receiver operating characteristic curve = 0.71) for psychiatric SA. Distress was a valid prognostic risk marker for identifying office workers at work, but at risk of future psychiatric SA. Further research is necessary to investigate the prognostic performance of distress as risk marker of psychiatric SA in other working populations and to determine cut-off points for distress.

Development of multiplex microsatellite PCR panels for the seagrass Thalassia hemprichii (Hydrocharitaceae).

PubMed

van Dijk, Kor-Jent; Mellors, Jane; Waycott, Michelle

2014-11-01

New microsatellites were developed for the seagrass Thalassia hemprichii (Hydrocharitaceae), a long-lived seagrass species that is found throughout the shallow waters of tropical and subtropical Indo-West Pacific. Three multiplex PCR panels were designed utilizing new and previously developed markers, resulting in a toolkit for generating a 16-locus genotype. • Through the use of microsatellite enrichment and next-generation sequencing, 16 new, validated, polymorphic microsatellite markers were isolated. Diversity was between two and four alleles per locus totaling 36 alleles. These markers, plus previously developed microsatellite markers for T. hemprichii and T. testudinum, were tested for suitability in multiplex PCR panels. • The generation of an easily replicated suite of multiplex panels of codominant molecular markers will allow for high-resolution and detailed genetic structure analysis and clonality assessment with minimal genotyping costs. We suggest the establishment of a T. hemprichii primer convention for the unification of future data sets.

Physicochemical assessment criteria for high-voltage pulse capacitors

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

Darian, L. A., E-mail: LDarian@rambler.ru; Lam, L. Kh.

In the paper, the applicability of decomposition products of internal insulation of high-voltage pulse capacitors is considered (aging is the reason for decomposition products of internal insulation). Decomposition products of internal insulation of high-voltage pulse capacitors can be used to evaluate their quality when in operation and in service. There have been three generations of markers of aging of insulation as in the case with power transformers. The area of applicability of markers of aging of insulation for power transformers has been studied and the area can be extended to high-voltage pulse capacitors. The research reveals that there is amore » correlation between the components and quantities of markers of aging of the first generation (gaseous decomposition products of insulation) dissolved in insulating liquid and the remaining life of high-voltage pulse capacitors. The application of markers of aging to evaluate the remaining service life of high-voltage pulse capacitor is a promising direction of research, because the design of high-voltage pulse capacitors keeps stability of markers of aging of insulation in high-voltage pulse capacitors. It is necessary to continue gathering statistical data concerning development of markers of aging of the first generation. One should also carry out research aimed at estimation of the remaining life of capacitors using markers of the second and the third generation.« less

Minefield reconnaissance and detector system

DOEpatents

Butler, M.T.; Cave, S.P.; Creager, J.D.; Johnson, C.M.; Mathes, J.B.; Smith, K.J.

1994-04-26

A multi-sensor system is described for detecting the presence of objects on the surface of the ground or buried just under the surface, such as anti-personnel or anti-tank mines or the like. A remote sensor platform has a plurality of metal detector sensors and a plurality of short pulse radar sensors. The remote sensor platform is remotely controlled from a processing and control unit and signals from the remote sensor platform are sent to the processing and control unit where they are individually evaluated in separate data analysis subprocess steps to obtain a probability score for each of the pluralities of sensors. These probability scores are combined in a fusion subprocess step by comparing score sets to a probability table which is derived based upon the historical incidence of object present conditions given that score set. A decision making rule is applied to provide an output which is optionally provided to a marker subprocess for controlling a marker device to mark the location of found objects. 7 figures.

Localization of new, microdissection- generated, anonymous markers and of the genes Pcsk1, Dhfr, Ndub13, and Ccnb1 to rat chromosome region 2q1.

PubMed

Quan, X; Laes, J F; Ravoet, M; Van Vooren, P; Szpirer, J; Szpirer, C

2000-01-01

The centromeric region of rat chromosome 2 (2q1) harbors unidentified quantitative trait loci of genes that control tumor growth or development. To improve the mapping of this chromosome region, we microdissected it and generated 10 new microsatellite markers, which we included in the linkage map and/or radiation hybrid map of 2q1, together with other known markers, including four genes: Pcsk1 (protein convertase 1), Dhfr (dihydrofolate reductase), Ndub13 (NADH ubiquinone oxidoreductase subunit b13), and Ccnb1 (cyclin B1). To generate anchor points between the different maps, the gene Ndub13 and the microsatellite markers D2Ulb25 and D2Mit1 were also localized cytogenetically. The radiation map generated in region 2q1 extends its centromeric end of about 150 cR. Copyright 2000 S. Karger AG, Basel

Mach-zehnder based optical marker/comb generator for streak camera calibration

DOEpatents

Miller, Edward Kirk

2015-03-03

This disclosure is directed to a method and apparatus for generating marker and comb indicia in an optical environment using a Mach-Zehnder (M-Z) modulator. High speed recording devices are configured to record image or other data defining a high speed event. To calibrate and establish time reference, the markers or combs are indicia which serve as timing pulses (markers) or a constant-frequency train of optical pulses (comb) to be imaged on a streak camera for accurate time based calibration and time reference. The system includes a camera, an optic signal generator which provides an optic signal to an M-Z modulator and biasing and modulation signal generators configured to provide input to the M-Z modulator. An optical reference signal is provided to the M-Z modulator. The M-Z modulator modulates the reference signal to a higher frequency optical signal which is output through a fiber coupled link to the streak camera.

Functional markers based molecular characterization and cloning of resistance gene analogs encoding NBS-LRR disease resistance proteins in finger millet (Eleusine coracana).

PubMed

Panwar, Preety; Jha, Anand Kumar; Pandey, P K; Gupta, Arun K; Kumar, Anil

2011-06-01

Magnaporthe grisea, the blast fungus is one of the main pathological threats to finger millet crop worldwide. A systematic search for the blast resistance gene analogs was carried out, using functional molecular markers. Three-fourths of the recognition-dependent disease resistance genes (R-genes) identified in plants encodes nucleotide binding site (NBS) leucine-rich repeat (LRR) proteins. NBS-LRR homologs have only been isolated on a limited scale from Eleusine coracana. Genomic DNA sequences sharing homology with NBS region of resistance gene analogs were isolated and characterized from resistant genotypes of finger millet using PCR based approach with primers designed from conserved regions of NBS domain. Attempts were made to identify molecular markers linked to the resistance gene and to differentiate the resistant bulk from the susceptible bulk. A total of 9 NBS-LRR and 11 EST-SSR markers generated 75.6 and 73.5% polymorphism respectively amongst 73 finger millet genotypes. NBS-5, NBS-9, NBS-3 and EST-SSR-04 markers showed a clear polymorphism which differentiated resistant genotypes from susceptible genotypes. By comparing the banding pattern of different resistant and susceptible genotypes, five DNA amplifications of NBS and EST-SSR primers (NBS-05(504,) NBS-09(711), NBS-07(688), NBS-03(509) and EST-SSR-04(241)) were identified as markers for the blast resistance in resistant genotypes. Principal coordinate plot and UPGMA analysis formed similar groups of the genotypes and placed most of the resistant genotypes together showing a high level of genetic relatedness and the susceptible genotypes were placed in different groups on the basis of differential disease score. Our results provided a clue for the cloning of finger millet blast resistance gene analogs which not only facilitate the process of plant breeding but also molecular characterization of blast resistance gene analogs from Eleusine coracana.

Marker development

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

Adams, M.R.

This report is to discuss the marker development for radioactive waste disposal sites. The markers must be designed to last 10,000 years, and place no undue burdens on the future generations. Barriers cannot be constructed that preclude human intrusion. Design specifications for surface markers will be discussed, also marker pictograms will also be covered.

Acculturation, immigration status and cardiovascular risk factors among Portuguese immigrants to Luxembourg: findings from ORISCAV-LUX study.

PubMed

Alkerwi, Ala'a; Sauvageot, Nicolas; Pagny, Sybil; Beissel, Jean; Delagardelle, Charles; Lair, Marie-Lise

2012-10-11

No previous study has examined the prevalence of cardiovascular risk factors and explored the influence of immigration status and acculturation on overweight/obesity among the Portuguese immigrants to Luxembourg. Our objectives were to (1) compare the prevalence of cardiovascular risk factors between native Luxembourgers and Portuguese immigrants, (2) examine the relationship between immigrant generation status, proportion of life spent in Luxembourg and language proficiency or preference (as proxy variables of acculturation) and overweight/obesity among Portuguese immigrants, and (3) elucidate the role of underlying socioeconomic, behavioral and dietary factors in overweight/obesity differences among the two populations. Recent national cross-sectional data from ORISCAV-LUX survey 2007-2008, composed of 843 subjects were analyzed. Overweight/obesity was defined as body mass index (BMI) >25 kg/m(2). Acculturation score was measured by using immigrant generation status, proportion of life spent in Luxembourg, and language proficiency or preference. Univariable and multivariable logistic regression analyses were performed to examine the association between acculturation markers and overweight/obesity. Further, a series of successive models were fitted to explore the separated and added impact of potential mediators (socioeconomic status, physical activity, dietary factors) on overweight/obesity among Luxembourgers and Portuguese immigrants. Compared to Luxembourgers, Portuguese immigrants of first and second generation were younger and currently employed. About 68% of first generation Portuguese had only primary school, and about 44% were living below poverty threshold. Although the cardiovascular risk factors were comparable, Portuguese immigrants were more frequently overweight and obese than Luxembourgers, even after age and gender standardization to the European population. Overweight/obesity was significantly higher among Portuguese of first generation compared to second generation (P=0.028). Although we observed a tendency of lower risk with higher acculturation, none of the acculturation markers, both individually and taken together as a score, was statistically significant after controlling for age and gender. Compared to Luxembourgers, odds of overweight/obesity were significantly higher among Portuguese immigrants, in unadjusted model 1 (P=0.043), in age and gender-adjusted model 2 (P<0.0001), in socioeconomic status adjusted model 3 (P= 0.01), in physical activity adjusted model 4 (P=0.007). However, this difference was attenuated and statistically disappeared after controlling for dietary factors (P=0.09). These findings address a lack of heterogeneity between Portuguese immigrants and Luxembourgers regarding hypertension, hyperlipidemia, diabetes mellitus, physical inactivity, and current cigarette smoking. However, Portuguese immigrants to Luxembourg were more likely to be overweight/obese than Luxembourgers participants. This risk may be explained by different dietary practice. An in-depth comparative assessment of dietary habits of Luxembourgers and Portuguese immigrants is warranted.

Acculturation, immigration status and cardiovascular risk factors among Portuguese immigrants to Luxembourg: findings from ORISCAV-LUX study

PubMed Central

2012-01-01

Background No previous study has examined the prevalence of cardiovascular risk factors and explored the influence of immigration status and acculturation on overweight/obesity among the Portuguese immigrants to Luxembourg. Our objectives were to (1) compare the prevalence of cardiovascular risk factors between native Luxembourgers and Portuguese immigrants, (2) examine the relationship between immigrant generation status, proportion of life spent in Luxembourg and language proficiency or preference (as proxy variables of acculturation) and overweight/obesity among Portuguese immigrants, and (3) elucidate the role of underlying socioeconomic, behavioral and dietary factors in overweight/obesity differences among the two populations. Methods Recent national cross-sectional data from ORISCAV-LUX survey 2007–2008, composed of 843 subjects were analyzed. Overweight/obesity was defined as body mass index (BMI) >25kg/m2. Acculturation score was measured by using immigrant generation status, proportion of life spent in Luxembourg, and language proficiency or preference. Univariable and multivariable logistic regression analyses were performed to examine the association between acculturation markers and overweight/obesity. Further, a series of successive models were fitted to explore the separated and added impact of potential mediators (socioeconomic status, physical activity, dietary factors) on overweight/obesity among Luxembourgers and Portuguese immigrants. Results Compared to Luxembourgers, Portuguese immigrants of first and second generation were younger and currently employed. About 68% of first generation Portuguese had only primary school, and about 44% were living below poverty threshold. Although the cardiovascular risk factors were comparable, Portuguese immigrants were more frequently overweight and obese than Luxembourgers, even after age and gender standardization to the European population. Overweight/obesity was significantly higher among Portuguese of first generation compared to second generation (P=0.028). Although we observed a tendency of lower risk with higher acculturation, none of the acculturation markers, both individually and taken together as a score, was statistically significant after controlling for age and gender. Compared to Luxembourgers, odds of overweight/obesity were significantly higher among Portuguese immigrants, in unadjusted model 1 (P=0.043), in age and gender-adjusted model 2 (P<0.0001), in socioeconomic status adjusted model 3 (P= 0.01), in physical activity adjusted model 4 (P=0.007). However, this difference was attenuated and statistically disappeared after controlling for dietary factors (P=0.09). Conclusions These findings address a lack of heterogeneity between Portuguese immigrants and Luxembourgers regarding hypertension, hyperlipidemia, diabetes mellitus, physical inactivity, and current cigarette smoking. However, Portuguese immigrants to Luxembourg were more likely to be overweight/obese than Luxembourgers participants. This risk may be explained by different dietary practice. An in-depth comparative assessment of dietary habits of Luxembourgers and Portuguese immigrants is warranted. PMID:23057477

Diet Quality Is Linked to Insulin Resistance among Adults in China.

PubMed

Wang, Zhihong; Adair, Linda S; Cai, Jianwen; Gordon-Larsen, Penny; Siega-Riz, Anna Maria; Zhang, Bing; Popkin, Barry M

2017-11-01

Background: Little is known about the impact of Chinese diet quality changes on diabetes-related markers. Objective: The present study examined the association of changes in overall diet quality with various biomarkers of diabetes among adults in China. Methods: The current analysis used longitudinal diet data from 1991 to 2006 and fasting blood samples from 2009 for 4734 adults aged 18-65 y from the China Health and Nutrition Survey. Dietary intake was assessed by using 3 consecutive 24-h recalls and household food weighing. The tailored Alternative Healthy Eating Index (tAHEI) was adapted from the 2010 Harvard Alternative Healthy Eating Index to measure overall diet quality. We categorized baseline tAHEI scores into tertiles and annual changes in the scores into 5 levels (high decrease, low decrease, maintain, low increase, and high increase). We performed mixed-effects regressions to assess the associations between baseline scores and changes in the tAHEI scores and diabetes or insulin markers. Results: Adults with high baseline tAHEI scores tended to be male, older, of lower socioeconomic status, and with higher physical activity levels. After adjustment for all of the covariates, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) values were 5.1% (95% CI: -0.100, -0.002) and 5.7% (95% CI: -0.113, -0.001) lower, respectively, for adults with high compared with low baseline tAHEI scores and 8.6% (95% CI: -0.155, -0.017) and 9.8% (95% CI: -0.177, -0.018) lower, respectively, for adults with a high increase in score compared with the "maintain" category. Null associations were observed between baseline scores and changes in the scores and fasting blood glucose, glycated hemoglobin (HbA1c), and diabetes prevalence. Conclusions: Baseline and changes in diet quality were independently associated with lower HOMA-IR and plasma insulin but not with fasting blood glucose and HbA1c in Chinese adults. Prospective studies on overall diet quality in relation to diabetes markers and risk of diabetes are needed. © 2017 American Society for Nutrition.

Development of next-generation mapping populations: Multi-parent Advanced Generation Inter-Cross (MAGIC) and Marker-Assisted Recurrent Selection (MARS) populations in peanut

USDA-ARS?s Scientific Manuscript database

Generation Inter-Cross (MAGIC) and Marker-Assisted Recurrent Selection (MARS) have been proposed and used in many crops to dissect complex traits or QTL. MAGIC allows for dissecting genomic structure, and for improving breeding populations by integrating multiple alleles from different parents. MAR...

Linkage studies on chromosome 22 in familial schizophrenia

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

Vallada, H.P.; Gill, M.; Sham, P.

1995-04-24

As part of a systematic search for a major genetic locus for schizophrenia we have examined chromosome 22 using 14 highly polymorphic markers in 23 disease pedigrees. The markers were distributed at an average distance of 6.6 cM, covering 70-80% of the chromosome. We analyzed the data by the lod score method using five plausible genetic models ranging from dominant to recessive, after testing the power of our sample under the same genetic parameters. The most positive lod score found was 1.51 under a recessive model for the marker D22S278, which is insufficient to conclude linkage. However, an excess ofmore » shared alleles in affected siblings (P < .01) was found for both D22S278 and D22S283. For D22S278, the A statistic was equal to the lod score (1.51) and therefore did not provide additional evidence for linkage allowing for heterogeneity, but the Liang statistic was more significant (P = .002). Our results suggest the possibility that the region around D22S278 and D22S283 contains a gene which contributes to the etiology of schizophrenia. 60 refs., 1 fig., 5 tabs.« less

N-Terminal Pro-B-Type Natriuretic Peptide and Subclinical Brain Damage in the General Population.

PubMed

Zonneveld, Hazel I; Ikram, M Arfan; Hofman, Albert; Niessen, Wiro J; van der Lugt, Aad; Krestin, Gabriel P; Franco, Oscar H; Vernooij, Meike W

2017-04-01

Purpose To investigate the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP), which is a marker of heart disease, and markers of subclinical brain damage on magnetic resonance (MR) images in community-dwelling middle-aged and elderly subjects without dementia and without a clinical diagnosis of heart disease. Materials and Methods This prospective population-based cohort study was approved by a medical ethics committee overseen by the national government, and all participants gave written informed consent. Serum levels of NT-proBNP were measured in 2397 participants without dementia or stroke (mean age, 56.6 years; age range, 45.7-87.3 years) and without clinical diagnosis of heart disease who were drawn from the population-based Rotterdam Study. All participants were examined with a 1.5-T MR imager. Multivariable linear and logistic regression analyses were used to investigate the association between NT-proBNP level and MR imaging markers of subclinical brain damage, including volumetric, focal, and microstructural markers. Results A higher NT-proBNP level was associated with smaller total brain volume (mean difference in z score per standard deviation increase in NT-proBNP level, -0.021; 95% confidence interval [CI]: -0.034, -0.007; P = .003) and was predominantly driven by gray matter volume (mean difference in z score per standard deviation increase in NT-proBNP level, -0.037; 95% CI: -0.057, -0.017; P < .001). Higher NT-proBNP level was associated with larger white matter lesion volume (mean difference in z score per standard deviation increase in NT-proBNP level, 0.090; 95% CI: 0.051, 0.129; P < .001), with lower fractional anisotropy (mean difference in z score per standard deviation increase in NT-proBNP level, -0.048; 95% CI: -0.088, -0.008; P = .019) and higher mean diffusivity (mean difference in z score per standard deviation increase in NT-proBNP level, 0.054; 95% CI: 0.018, 0.091; P = .004) of normal-appearing white matter. Conclusion In community-dwelling persons, higher serum NT-proBNP levels are associated with volumetric and microstructural MR imaging markers of subclinical brain damage. © RSNA, 2016 Online supplemental material is available for this article.

TSPmap, a tool making use of traveling salesperson problem solvers in the efficient and accurate construction of high-density genetic linkage maps.

PubMed

Monroe, J Grey; Allen, Zachariah A; Tanger, Paul; Mullen, Jack L; Lovell, John T; Moyers, Brook T; Whitley, Darrell; McKay, John K

2017-01-01

Recent advances in nucleic acid sequencing technologies have led to a dramatic increase in the number of markers available to generate genetic linkage maps. This increased marker density can be used to improve genome assemblies as well as add much needed resolution for loci controlling variation in ecologically and agriculturally important traits. However, traditional genetic map construction methods from these large marker datasets can be computationally prohibitive and highly error prone. We present TSPmap , a method which implements both approximate and exact Traveling Salesperson Problem solvers to generate linkage maps. We demonstrate that for datasets with large numbers of genomic markers (e.g. 10,000) and in multiple population types generated from inbred parents, TSPmap can rapidly produce high quality linkage maps with low sensitivity to missing and erroneous genotyping data compared to two other benchmark methods, JoinMap and MSTmap . TSPmap is open source and freely available as an R package. With the advancement of low cost sequencing technologies, the number of markers used in the generation of genetic maps is expected to continue to rise. TSPmap will be a useful tool to handle such large datasets into the future, quickly producing high quality maps using a large number of genomic markers.

Fermented whey-based product improves the quality of life of males with moderate lower urinary tract symptoms: A randomized double-blind study.

PubMed

Ausmees, Kristo; Ehrlich-Peets, Kersti; Vallas, Mirjam; Veskioja, Andre; Rammul, Kadi; Rehema, Aune; Zilmer, Mihkel; Songisepp, Epp; Kullisaar, Tiiu

2018-01-01

The purpose of this research was to evaluate the effect of a specific fermented whey product on lower urinary tract symptoms, main prostate related indices and oxidative stress/inflammatory markers in urine and seminal plasma in men with moderate dysuric symptoms. An additional purpose was to clarify associations between different parameters with special emphasis on pain. This was a prospective randomized double-blind 4-weeks study on men with moderate lower urinary tract symptoms who underwent the evaluation for quality of life at the baseline and at the end of the study. The symptoms were characterized by International Prostate Symptom Score (I-PSS) and National Institutes of Health Chronic Prostatitis Symptom Index (NIH-PSI), the maximum urinary flow and the main prostate-related indices. In order to obtain more comprehensive information about the effects of fermented whey product on systemic oxidative stress marker 8-EPI and seminal plasma inflammatory markers (interleukin-6 and interleukin-8) were also measured. After 4 weeks consumption of fermented whey product there was a statistically significant decrease of prostate-specific antigen level in serum and systemic stress marker 8-EPI in urine compared to control group. Maximum urinary flow and NIH-PSI all studied scores and sub-scores had also significant improvement. In addition, seminal plasma interleukin-8 level substantially decreased. The consumption of special fermented whey product improved urinary function, reduced lower urinary tract symptoms, systemic oxidative stress marker and seminal plasma inflammatory status. Thus it contributed to an improvement of the quality of life in men with moderate lower urinary tract symptoms.

Computer-Generated Feedback on Student Writing

ERIC Educational Resources Information Center

Ware, Paige

2011-01-01

A distinction must be made between "computer-generated scoring" and "computer-generated feedback". Computer-generated scoring refers to the provision of automated scores derived from mathematical models built on organizational, syntactic, and mechanical aspects of writing. In contrast, computer-generated feedback, the focus of this article, refers…

Relationships between appetite and quality of life in hemodialysis patients.

PubMed

Zabel, Rachel; Ash, Susan; King, Neil; Juffs, Philip; Bauer, Judith

2012-08-01

The aim of this paper was to investigate the association between appetite and kidney-disease specific quality of life in maintenance hemodialysis patients. Quality of life (QoL) was measured using the kidney disease quality of life survey. Appetite was measured using self-reported categories and a visual analog scale. Other nutritional parameters included Patient-Generated Subjective Global Assessment (PGSGA), dietary intake, body mass index and biochemical markers C-reactive protein and albumin. Even in this well nourished sample (n=62) of hemodialysis patients, PGSGA score (r=-0.629), subjective hunger sensations (r=0.420) and body mass index (r=-0.409) were all significantly associated with the physical health domain of QoL. As self-reported appetite declined, QoL was significantly lower in nine domains which were mostly in the SF36 component and covered social functioning and physical domains. Appetite and other nutritional parameters were not as strongly associated with the Mental Health domain and Kidney Disease Component Summary Domains. Nutritional parameters, especially PGSGA score and appetite, appear to be important components of the physical health domain of QoL. As even small reductions in nutritional status were associated with significantly lower QoL scores, monitoring appetite and nutritional status is an important component of care for hemodialysis patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

Non-Eosinophilic Nasal Polyps Shows Increased Epithelial Proliferation and Localized Disease Pattern in the Early Stage.

PubMed

Kim, Dong-Kyu; Jin, Hong Ryul; Eun, Kyoung Mi; Mutusamy, Somasundran; Cho, Seong H; Oh, Sohee; Kim, Dae Woo

2015-01-01

Non-eosinophilic nasal polyps (NPs) show less inflammatory changes and are less commonly associated with lower airway inflammatory disorders such as asthma, compared with eosinophilic NPs. However, the development of non-eosinophilic NPs which is a predominant subtype in Asian population still remains unclear. A total of 81 patients (45 with non-eosinophilic NPs and 36 with eosinophilic NPs) were enrolled. Clinical information and computed tomography (CT), endoscopic, and histological findings were investigated. Tissue samples were analyzed for total IgE levels and for mRNA expression levels of interleukin (IL)-4, IL-5, IL-13, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-17A, IL-22, IL-23p19, transforming growth factor (TGF)-β1, TGF-β2, TGF-β3, and periostin. Immunostaining assessment of Ki-67 as a proliferation marker was performed. We found that epithelial in-growing patterns such as pseudocysts were more frequently observed in histological and endoscopic evaluations of non-eosinophilic NPs, which was linked to increase epithelial staining of Ki-67, a proliferating marker. Eosinophilic NPs were characterized by high infiltration of inflammatory cells, compared with non-eosinophilic NPs. To investigate the developmental course of each subtype, CT was analyzed according to CT scores and subtypes. Non-eosinophilic NPs showed more localized pattern and maxillary sinus involvement, but lesser olfactory involvement in early stage whereas eosinophilic NPs were characterized by diffuse ethmoidal and olfactory involvement. In addition, high ethmoidal/maxillary (E/M) CT scores, indicating ethmoidal dominant involvement, were one of surrogate markers for eosinophilic NP. E/M CT scores was positively correlated with levels of TH2 inflammatory markers, including IL-4, IL-5, periostin mRNA expression and total IgE levels in NPs, whereas levels of the TH1 cytokine, IFN- γ were inversely correlated. Moreover, if the combinatorial algorithm meet the three of the four markers, including IL-5 (<2.379), periostin (<3.889), IFN-γ (>0.316), and E/M ratio (<2.167), non-eosinophilic CRSwNP are diagnosed with a sensitivity of 84.4% and a specificity of 84.8%. Histologic, immunologic and clinical data suggest that non-eosinophilic NPs showed enhanced epithelial alteration and more localized maxillary involvement. Combination of cutoff value on IL-5, periostin, IFN-γ, and E/M scores may be one of surrogate markers for non-eosinophil NP subtype.

Neutrophil contribution to the crescentic glomerulonephritis in SCG/Kj mice.

PubMed

Ishida-Okawara, Akiko; Ito-Ihara, Toshiko; Muso, Eri; Ono, Takahiko; Saiga, Kan; Nemoto, Kyuichi; Suzuki, Kazuo

2004-07-01

Myeloperoxidase-specific anti-neutrophil cytoplasmic auto-antibody (MPO-ANCA) has been a useful diagnostic marker in systemic vasculitis with crescentic glomerulonephritis (CrGN). It is highly suspected that the antigenic enzyme MPO released from activated neutrophils is involved in these lesions. We evaluated the relationship between neutrophil functions including peripheral neutrophil counts and renal lesions in SCG/Kj mice as a model of ANCA-associated CrGN and vasculitis. Peripheral neutrophil counts, the plasma levels of MPO-ANCA and tumour necrosis factor alpha (TNF-alpha) were measured. The capacity of MPO release and superoxide generation were evaluated as neutrophil activity. The renal lesions were estimated by grade of proteinuria, histopathological lesion, such as glomerular neutrophil infiltration and active or chronic renal injury scores with crescent formation. MPO-ANCA and TNF-alpha levels were higher than those of normal mice C57BL/6 even before overt proteinuria; subsequently, peripheral neutrophils increased. In the phase of nephritis with low grade proteinuria, the spontaneous release of MPO from peripheral neutrophils increased, while superoxide generation increased before spontaneous MPO release occurred. In addition, the renal lesion in histological observations was aggravated with ageing and the glomerular neutrophil infiltration was positively correlated with MPO-ANCA levels, as well as with histological indices of nephritis, active renal injury score; in particular, crescent formation was correlated with spontaneous MPO release. In contrast, superoxide generation was negatively correlated with the severity of this lesion during the progression. These findings indicate that neutrophils are activated and contribute to the development of the active crescentic lesion in SCG/Kj mice.

Serum Levels of Inflammatory Markers in Depressed Elderly Patients with Diabetes and Mild Cognitive Impairment

PubMed Central

Gorska-Ciebiada, Malgorzata; Saryusz-Wolska, Malgorzata; Borkowska, Anna; Ciebiada, Maciej; Loba, Jerzy

2015-01-01

Objective The aim of the study was to determine the serum levels of CRP, IL-6 and TNF-α in elderly diabetic patients with depressive syndrome alone or with coexisting mild cognitive impairment (MCI). Methods 276 diabetics elders were screened for depressive symptoms (using Geriatric Depression Scale: GDS-30) and MCI (using the Montreal Cognitive Assessment: MoCA score). Data of HbA1c, blood lipids and inflammatory markers levels were collected. Results In all groups of patients levels of CRP, IL-6 and TNF-α were significantly higher as compared to controls. The highest level of inflammatory markers was detected in group with depressive mood and coexisting MCI, however IL-6 level didn’t significantly differ as compared to MCI group. We founded correlations between all inflammatory markers in group of patients with depressive mood and in group of subjects with depressive symptoms and coexisting MCI. GDS-30 score was correlated with levels of inflammatory markers in group with depressive mood, and with levels of CRP and TNF-α in group with depressive mood and coexisting MCI. In the group with depressive mood and coexisting MCI we founded that MoCA score was negatively correlated with CRP and TNF-α levels; and HbA1c level was positively correlated with all inflammatory markers. The univariate logistic regression models revealed that variables which increased the likelihood of having been diagnosed with MCI in depressed patients were: higher levels of HbA1c, CRP, IL-6 and TNF-α, previous CVD or stroke, increased number of co-morbidities and microvascular complications, older age, less years of formal education. The multivariable model showed that previous CVD, higher HbA1c and IL-6 levels are significant factors. Conclusions We demonstrated that the presence of depressive syndrome is associated with higher levels of inflammatory markers in elderly patients with diabetes. The presence of MCI in these depressed subjects has additive effect on levels of inflammatory mediators. PMID:25793613

μ-Calpain (CAPN1), calpastatin (CAST), and growth hormone receptor (GHR) genetic effects on Angus beef heifer performance traits and reproduction.

PubMed

Tait, Richard G; Cushman, Robert A; McNeel, Anthony K; Casas, Eduardo; Smith, Timothy P L; Freetly, Harvey C; Bennett, Gary L

2018-06-01

Genetic marker effects and type of inheritance are estimated with poor precision when minor marker allele frequencies are low. An Angus population was subjected to marker assisted selection for multiple years to equalize CAPN1 haplotypes, CAST, and GHR genetic marker frequencies. The objective was to estimate the pleiotropic effects of these carcass quality oriented markers for body weight, reproduction, and first calf performance traits in 174 replacement beef females which were managed under 2 post-weaning development protocols. Heifers were weighed at 11-, 12-, and 13-mo, at first breeding season pregnancy evaluation, and prior to first calving season. Pubertal status was determined at 11-, 12-, and 13-mo of age. Antral follicles were counted, reproductive tracts were scored, and tract dimensions were measured at 13-mo. Body condition and hip height were scored and measured at pregnancy evaluation and prior to calving season. Heifer pregnancy and weaning rates and ordinal birth date were recorded. Calf body weights at birth and weaning were analyzed. Single df linear contrasts for recessive effects of the GHR heterozygous genotype showed significant decreases of 2.5-3.6% in 11-, 12-, and 13-mo heifer body weights and heifer weight prior to calving. The additive differences between GHR homozygotes were small and not significant for all body weights measured but a 1 wk difference in calf birth date was significant. For all 13-mo uterine measurements, scores, and antral follicle counts, only the CAST dominance contrast for medium antral follicle count was significant. The CAPN1 haplotype with a strong additive effect for increased beef tenderness also had a significant additive effect on calving date. Heifers homozygous for the tender haplotype calved 7.9 days later than heifers homozygous for the tough haplotype. Most heifer reproductive traits were not significantly affected by CAST and CAPN1 markers that are widely used to improve beef tenderness by selection and breeders should not be concerned with how these markers affect reproduction and other heifer traits with the possible exception of CAPN1 effects on calving date. Published by Elsevier Inc.

Osteoporosis and Osteopathy Markers in Patients with Mastocytosis

PubMed Central

Alpay Kanıtez, Nilüfer; Erer, Burak; Doğan, Öner; Büyükbabani, Nesimi; Baykal, Can; Sindel, Dilşad; Tanakol, Refik; Yavuz, Akif Selim

2015-01-01

Objective: Osteoporosis, osteosclerosis, and lytic bone lesions have been observed in patients with systemic mastocytosis (SM). We examined bone mineral density (BMD) biochemical turnover markers and serum tryptase levels in SM, which is considered a rare disease. Materials and Methods: Seventeen adult patients (5 females, 12 males; median age: 33 years, range: 20-64) with mastocytosis were included in this study. We investigated the value of quantitative ultrasound (QUS) of the calcaneus in the assessment of BMD in SM patients, as well as BMD of the lumbar spine (L1-L4), femoral neck, and distal radius using dual energy x-ray absorptiometry (DXA) and plasma tryptase levels, biochemical markers of bone turnover. Results: At lumbar spine L1-L4, the femoral neck, and the distal radius or as calcaneus stiffness, 12 of 17 patients had T-scores of less than -1 at least at 1 site, reflecting osteopenia. Three of 17 patients had T-scores showing osteoporosis (T-score <-2.5). There was no relationship between DXA and bone lesion severity. We also found a significant positive correlation between tryptase levels and disease severity, as well as between disease severity and pyridinoline (p<0.01 by Spearman’s test). Conclusion: DXA and calcaneal QUS may not be appropriate techniques to assess bone involvement in SM patients because of the effects of osteosclerosis. This study further shows that the osteoclastic marker pyridinoline is helpful in patients with severe disease activity and sclerotic bone lesions to show bone demineralization. PMID:25805674

STRP linkage studies in a new family with X-linked mental retardation: Tight linkage to DXS458

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

Lazzarini, A.; Stenroos, E.S.; Lehner, T.

1994-09-01

Isolated or non-specific mental retardation is defined as {open_quote}non-progressive intellectual handicap segregating in an X-linked manner without any consistent somatic or diagnostic features{close_quote}. The Human Gene Mapping Nomenclature Committee sequentially designates each newly reported MRX family, MRX1, MRX2,... etc. when a lod score of +2 is demonstrated between the MR locus and one or more X chromosome markers. A family, designated MRX20, was studied with nine short tandem repeat polymorphism (STRP) markers. Two-point lod scores above 3 were obtained with DXYS1 (Z = 3.02, {theta} = 0), DX3 (Z = 3.22, {theta} = 0), and DXS458 (Z = 3.31, {theta}more » = 0). A multipoint lod score of 3.66 was obtained with a peak between DXS3 and DXS458, 1.1cM distal to DXS3. A one-unit support interval is 16 cM between PGK1 and DXS458. This family represents the ninth of fourteen reported MRX families linked to markers in the region of DXYS1, perhaps reflecting a cluster of genes involved in brain function. The identification of genetic markers linked to the disease-causing gene has allowed gene carrier risk assessment for females in the family. Future research will concentrate on comparing the diversity of haplotypes containing the disease genes in different families, on physical mapping of the region, and on isolation of the MRX 20 gene.« less

Coronary Artery Calcium as an Independent Surrogate Marker in the Risk Assessment of Patients With Atrial Fibrillation and an Intermediate Pretest Likelihood for Coronary Artery Disease Admitted to a German Chest Pain Unit.

PubMed

Breuckmann, Frank; Olligs, Jan; Hinrichs, Liane; Koopmann, Matthias; Lichtenberg, Michael; Böse, Dirk; Fischer, Dieter; Eckardt, Lars; Waltenberger, Johannes; Garvey, J Lee

2016-03-01

About 10% of patients admitted to a chest pain unit (CPU) exhibit atrial fibrillation (AF). To determine whether calcium scores (CS) are superior over common risk scores for coronary artery disease (CAD) in patients presenting with atypical chest pain, newly diagnosed AF, and intermediate pretest probability for CAD within the CPU. In 73 subjects, CS was related to the following risk scores: Global Registry of Acute Coronary Events (GRACE) score, including a new model of a frequency-normalized approach; Thrombolysis In Myocardial Infarction score; European Society of Cardiology Systematic Coronary Risk Evaluation (SCORE); Framingham risk score; and Prospective Cardiovascular Münster Study score. Revascularization rates during index stay were assessed. Median CS was 77 (interquartile range, 1-270), with higher values in men and the left anterior descending artery. Only the modified GRACE (ρ = 0.27; P = 0.02) and the SCORE (ρ = 0.39; P < 0.005) were significantly correlated with CS, whereas the GRACE (τ = 0.21; P = 0.04) and modified GRACE (τ = 0.23; P = 0.02) scores were significantly correlated with percentile groups. Only the CS significantly discriminated between those with and without stenosis (P < 0.01). Apart from modified GRACE score, overall correlations between risk scores and calcium burden, as well as revascularization rates during index stay, were low. By contrast, the determination of CS may be used as an additional surrogate marker in risk stratification in AF patients with intermediate pretest likelihood for CAD admitted to a CPU. © 2016 Wiley Periodicals, Inc.

A MAGIC population-based genome-wide association study reveals functional association of GhRBB1_A07 gene with superior fiber quality in cotton

USDA-ARS?s Scientific Manuscript database

An Upland cotton multi-parent advanced generation inter-cross (MAGIC) population was developed through random-mating of 11 diverse cultivars for five generations. In this study, fiber quality data obtained from four environments and 6,071 SNP markers generated via GBS and 223 microsatellite markers...

Combining clinical and magnetic resonance imaging markers enhances prediction of 12-year disability in multiple sclerosis.

PubMed

Uher, Tomas; Vaneckova, Manuela; Sobisek, Lukas; Tyblova, Michaela; Seidl, Zdenek; Krasensky, Jan; Ramasamy, Deepa; Zivadinov, Robert; Havrdova, Eva; Kalincik, Tomas; Horakova, Dana

2017-01-01

Disease progression and treatment efficacy vary among individuals with multiple sclerosis. Reliable predictors of individual disease outcomes are lacking. To examine the accuracy of the early prediction of 12-year disability outcomes using clinical and magnetic resonance imaging (MRI) parameters. A total of 177 patients from the original Avonex-Steroids-Azathioprine study were included. Participants underwent 3-month clinical follow-ups. Cox models were used to model the associations between clinical and MRI markers at baseline or after 12 months with sustained disability progression (SDP) over the 12-year observation period. At baseline, T2 lesion number, T1 and T2 lesion volumes, corpus callosum (CC), and thalamic fraction were the best predictors of SDP (hazard ratio (HR) = 1.7-4.6; p ⩽ 0.001-0.012). At 12 months, Expanded Disability Status Scale (EDSS) and its change, number of new or enlarging T2 lesions, and CC volume % change were the best predictors of SDP over the follow-up (HR = 1.7-3.5; p ⩽  0.001-0.017). A composite score was generated from a subset of the best predictors of SDP. Scores of ⩾4 had greater specificity (90%-100%) and were associated with greater cumulative risk of SDP (HR = 3.2-21.6; p < 0.001) compared to the individual predictors. The combination of established MRI and clinical indices with MRI volumetric predictors improves the prediction of SDP over long-term follow-up and may provide valuable information for therapeutic decisions.

Polymorphic SSR Markers for Plasmopara obducens (Peronosporaceae), the Newly Emergent Downy Mildew Pathogen of Impatiens (Balsaminaceae)

DOE PAGES

Salgado-Salazar, Catalina; Rivera, Yazmín; Veltri, Daniel; ...

2015-11-10

Premise of the study: Simple sequence repeat (SSR) markers were developed for Plasmopara obducens, the causal agent of the newly emergent downy mildew disease of Impatiens walleriana. Methods and Results: A 202-Mb draft genome assembly was generated from P. obducens using Illumina technology and mined to identify 13,483 SSR motifs. Primers were synthesized for 62 marker candidates, of which 37 generated reliable PCR products. Testing of the 37 markers using 96 P. obducens samples showed 96% of the markers were polymorphic, with 2-6 alleles observed. Observed and expected heterozygosity ranged from 0.000-0.892 and 0.023-0.746, respectively. Just 17 markers were sufficientmore » to identify all multilocus genotypes. Conclusions: These are the first SSR markers available for this pathogen, and one of the first molecular resources. These markers will be useful in assessing variation in pathogen populations and determining the factors contributing to the emergence of destructive impatiens downy mildew disease.« less

Recurrent parent genome recovery analysis in a marker-assisted backcrossing program of rice (Oryza sativa L.).

PubMed

Miah, Gous; Rafii, Mohd Y; Ismail, Mohd R; Puteh, Adam B; Rahim, Harun A; Latif, Mohammad A

2015-02-01

Backcross breeding is the most commonly used method for incorporating a blast resistance gene into a rice cultivar. Linkage between the resistance gene and undesirable units can persist for many generations of backcrossing. Marker-assisted backcrossing (MABC) along with marker-assisted selection (MAS) contributes immensely to overcome the main limitation of the conventional breeding and accelerates recurrent parent genome (RPG) recovery. The MABC approach was employed to incorporate (a) blast resistance gene(s) from the donor parent Pongsu Seribu 1, the blast-resistant local variety in Malaysia, into the genetic background of MR219, a popular high-yielding rice variety that is blast susceptible, to develop a blast-resistant MR219 improved variety. In this perspective, the recurrent parent genome recovery was analyzed in early generations of backcrossing using simple sequence repeat (SSR) markers. Out of 375 SSR markers, 70 markers were found polymorphic between the parents, and these markers were used to evaluate the plants in subsequent generations. Background analysis revealed that the extent of RPG recovery ranged from 75.40% to 91.3% and from 80.40% to 96.70% in BC1F1 and BC2F1 generations, respectively. In this study, the recurrent parent genome content in the selected BC2F2 lines ranged from 92.7% to 97.7%. The average proportion of the recurrent parent in the selected improved line was 95.98%. MAS allowed identification of the plants that are more similar to the recurrent parent for the loci evaluated in backcross generations. The application of MAS with the MABC breeding program accelerated the recovery of the RP genome, reducing the number of generations and the time for incorporating resistance against rice blast. Copyright © 2014 Académie des sciences. Published by Elsevier SAS. All rights reserved.

No evidence for linkage between the X-chromosome marker DXS7 and schizophrenia

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

Okoro, C.; Bell, R.; Sham, P.

DeLisi et al. have examined the X and Y chromosomes for linkage to schizophrenia in 126 small families and report a small positive LOD score for the marker DXS7, adjacent to the MAO locus at Xp11.4-11.3. Because of this, we have examined the DXS7 for linkage to schizophrenia using 17 pedigrees in which male-to-male transmission of schizophrenia was absent. Alleles at DXS7 were genotyped using the PCR and LOD scores calculated using five models of inheritance, including classical dominant, recessive and intermediate models. LOD scores were substantially negative for all models examined and analysis for linkage heterogeneity using the LOD2more » method showed no significance. Analysis by the nonparametric affected sib-pair method likewise indicated no linkage. We conclude that DXS7 is not a major locus for schizophrenia in our collection of pedigrees. 29 refs., 1 tab.« less

Twenty-year Risk of Prostate Cancer Death by Midlife Prostate-specific Antigen and a Panel of Four Kallikrein Markers in a Large Population-based Cohort of Healthy Men.

PubMed

Sjoberg, Daniel D; Vickers, Andrew J; Assel, Melissa; Dahlin, Anders; Poon, Bing Ying; Ulmert, David; Lilja, Hans

2018-06-01

Prostate-specific antigen (PSA) screening reduces prostate cancer deaths but leads to harm from overdiagnosis and overtreatment. To determine the long-term risk of prostate cancer mortality using kallikrein blood markers measured at baseline in a large population of healthy men to identify men with low risk for prostate cancer death. Study based on the Malmö Diet and Cancer cohort enrolling 11 506 unscreened men aged 45-73 yr during 1991-1996, providing cryopreserved blood at enrollment and followed without PSA screening to December 31, 2014. We measured four kallikrein markers in the blood of 1223 prostate cancer cases and 3028 controls. Prostate cancer death (n=317) by PSA and a prespecified statistical model based on the levels of four kallikrein markers. Baseline PSA predicted prostate cancer death with a concordance index of 0.86. In men with elevated PSA (≥2.0ng/ml), predictive accuracy was enhanced by the four-kallikrein panel compared with PSA (0.80 vs 0.73; improvement 0.07; 95% confidence interval 0.04, 0.10). Nearly half of men aged 60+ yr with elevated PSA had a four-kallikrein panel score of <7.5%, translating into 1.7% risk of prostate cancer death at 15 yr-a similar estimate to that of a man with a PSA of 1.6ng/ml. Men with a four-kallikrein panel score of ≥7.5% had a 13% risk of prostate cancer death at 15 yr. A prespecified statistical model based on four kallikrein markers (commercially available as the 4Kscore) reclassified many men with modestly elevated PSA, to have a low long-term risk of prostate cancer death. Men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. Men with elevated prostate-specific antigen (PSA) are often referred for prostate biopsy. However, men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Development of multiplex microsatellite PCR panels for the seagrass Thalassia hemprichii (Hydrocharitaceae)1

PubMed Central

van Dijk, Kor-jent; Mellors, Jane; Waycott, Michelle

2014-01-01

• Premise of the study: New microsatellites were developed for the seagrass Thalassia hemprichii (Hydrocharitaceae), a long-lived seagrass species that is found throughout the shallow waters of tropical and subtropical Indo-West Pacific. Three multiplex PCR panels were designed utilizing new and previously developed markers, resulting in a toolkit for generating a 16-locus genotype. • Methods and Results: Through the use of microsatellite enrichment and next-generation sequencing, 16 new, validated, polymorphic microsatellite markers were isolated. Diversity was between two and four alleles per locus totaling 36 alleles. These markers, plus previously developed microsatellite markers for T. hemprichii and T. testudinum, were tested for suitability in multiplex PCR panels. • Conclusions: The generation of an easily replicated suite of multiplex panels of codominant molecular markers will allow for high-resolution and detailed genetic structure analysis and clonality assessment with minimal genotyping costs. We suggest the establishment of a T. hemprichii primer convention for the unification of future data sets. PMID:25383269

Large-scale mapping of mutations affecting zebrafish development.

PubMed

Geisler, Robert; Rauch, Gerd-Jörg; Geiger-Rudolph, Silke; Albrecht, Andrea; van Bebber, Frauke; Berger, Andrea; Busch-Nentwich, Elisabeth; Dahm, Ralf; Dekens, Marcus P S; Dooley, Christopher; Elli, Alexandra F; Gehring, Ines; Geiger, Horst; Geisler, Maria; Glaser, Stefanie; Holley, Scott; Huber, Matthias; Kerr, Andy; Kirn, Anette; Knirsch, Martina; Konantz, Martina; Küchler, Axel M; Maderspacher, Florian; Neuhauss, Stephan C; Nicolson, Teresa; Ober, Elke A; Praeg, Elke; Ray, Russell; Rentzsch, Brit; Rick, Jens M; Rief, Eva; Schauerte, Heike E; Schepp, Carsten P; Schönberger, Ulrike; Schonthaler, Helia B; Seiler, Christoph; Sidi, Samuel; Söllner, Christian; Wehner, Anja; Weiler, Christian; Nüsslein-Volhard, Christiane

2007-01-09

Large-scale mutagenesis screens in the zebrafish employing the mutagen ENU have isolated several hundred mutant loci that represent putative developmental control genes. In order to realize the potential of such screens, systematic genetic mapping of the mutations is necessary. Here we report on a large-scale effort to map the mutations generated in mutagenesis screening at the Max Planck Institute for Developmental Biology by genome scanning with microsatellite markers. We have selected a set of microsatellite markers and developed methods and scoring criteria suitable for efficient, high-throughput genome scanning. We have used these methods to successfully obtain a rough map position for 319 mutant loci from the Tübingen I mutagenesis screen and subsequent screening of the mutant collection. For 277 of these the corresponding gene is not yet identified. Mapping was successful for 80 % of the tested loci. By comparing 21 mutation and gene positions of cloned mutations we have validated the correctness of our linkage group assignments and estimated the standard error of our map positions to be approximately 6 cM. By obtaining rough map positions for over 300 zebrafish loci with developmental phenotypes, we have generated a dataset that will be useful not only for cloning of the affected genes, but also to suggest allelism of mutations with similar phenotypes that will be identified in future screens. Furthermore this work validates the usefulness of our methodology for rapid, systematic and inexpensive microsatellite mapping of zebrafish mutations.

Autosomal dominant cerebellar ataxia with retinal degeneration (ADCA II): clinical and neuropathological findings in two pedigrees and genetic linkage to 3p12-p21.1.

PubMed Central

Jöbsis, G J; Weber, J W; Barth, P G; Keizers, H; Baas, F; van Schooneveld, M J; van Hilten, J J; Troost, D; Geesink, H H; Bolhuis, P A

1997-01-01

OBJECTIVES: To investigate relations between clinical and neuropathological features and age of onset, presence of anticipation, and genetic linkage in autosomal dominant cerebellar ataxia type II (ADCA II). METHODS: The natural history of ADCA II was studied on the basis of clinical and neuropathological findings in two pedigrees and genetic linkage studies were carried out with polymorphic DNA markers in the largest, four generation, pedigree. RESULTS: Ataxia was constant in all age groups. Retinal degeneration with early extinction of the electroretinogram constituted an important component in juvenile and early adult (< 25 years) onset but was variable in late adult presentation. Neuromuscular involvement due to spinal anterior horn disease was an important contributing factor to illness in juvenile cases. Postmortem findings in four patients confirm the general neurodegenerative nature of the disease, which includes prominent spinal anterior horn involvement and widespread involvement of grey and white matter. Genetic linkage was found with markers to chromosome 3p12-p21.1 (maximum pairwise lod score 4.42 at D3S1285). CONCLUSIONS: The sequence of clinical involvement seems related to age at onset. Retinal degeneration is variable in late onset patients and neuromuscular features are important in patients with early onset. Strong anticipation was found in subsequent generations. Linkage of ADCA II to chromosome 3p12-p21.1 is confirmed. Images PMID:9120450

The Combined Influence of Air Pollution and Home Learning Environment on Early Cognitive Skills in Children

PubMed Central

Stingone, Jeanette A.

2017-01-01

Cognitive skills are one component of school readiness that reflect a child’s neurodevelopment and are influenced by environmental and social factors. Most studies assess the impact of these factors individually, without taking into consideration the complex interactions of multiple factors. The objective of this study was to examine the joint association of markers of environmental pollution and of social factors on early cognitive skills in an urban cohort of children. For this, we chose isophorone in ambient air as a marker of industrial air pollution. Low quality home learning environments was chosen as a marker of the social factors contributing to cognitive development. Using a subpopulation from the Early Childhood Longitudinal Study, Birth Cohort (N = 4050), isophorone exposure was assigned using the 2002 National Air Toxics Assessment. Home learning environment was assessed with a modified version of the Home Observation for Measurement of the Environment (HOME) Inventory, and standardized math assessment scores were used as a measure of early cognitive skills. Multiple linear regression was used to estimate the effect of both exposures on math scores. After adjustment for confounders, children living in areas with ambient isophorone in the upper quintile of exposure (>0.49 ng/m3) had math scores that were 1.63 points lower than their less exposed peers [95% CI: −2.91, −0.34], and children with lower HOME scores (at or below 9 out of 12) had math scores that were 1.20 points lower than children with better HOME scores [95% CI: −2.30, −0.10]. In adjusted models accounting for identified confounders and both exposures of interest, both high isophorone exposure and low HOME score remained independently associated with math scores [−1.48, 95% CI: −2.79, −0.18; −1.05, 95% CI: −2.15, 0.05, respectively]. There was no statistical evidence of interaction between the two exposures, although children with both higher isophorone exposure and a low HOME score had a decrement in math scale score beyond the additive effect of each exposure. This was primarily observed among male children. These findings suggest that aspects of both the physical and social environments are independently associated with children’s early cognitive skills. Future research aiming to improve children’s early cognitive skills and subsequent school readiness should address both domains. PMID:29072589

The Combined Influence of Air Pollution and Home Learning Environment on Early Cognitive Skills in Children.

PubMed

Lett, Lanair A; Stingone, Jeanette A; Claudio, Luz

2017-10-26

Cognitive skills are one component of school readiness that reflect a child's neurodevelopment and are influenced by environmental and social factors. Most studies assess the impact of these factors individually, without taking into consideration the complex interactions of multiple factors. The objective of this study was to examine the joint association of markers of environmental pollution and of social factors on early cognitive skills in an urban cohort of children. For this, we chose isophorone in ambient air as a marker of industrial air pollution. Low quality home learning environments was chosen as a marker of the social factors contributing to cognitive development. Using a subpopulation from the Early Childhood Longitudinal Study, Birth Cohort (N = 4050), isophorone exposure was assigned using the 2002 National Air Toxics Assessment. Home learning environment was assessed with a modified version of the Home Observation for Measurement of the Environment (HOME) Inventory, and standardized math assessment scores were used as a measure of early cognitive skills. Multiple linear regression was used to estimate the effect of both exposures on math scores. After adjustment for confounders, children living in areas with ambient isophorone in the upper quintile of exposure (>0.49 ng/m³) had math scores that were 1.63 points lower than their less exposed peers [95% CI: -2.91, -0.34], and children with lower HOME scores (at or below 9 out of 12) had math scores that were 1.20 points lower than children with better HOME scores [95% CI: -2.30, -0.10]. In adjusted models accounting for identified confounders and both exposures of interest, both high isophorone exposure and low HOME score remained independently associated with math scores [-1.48, 95% CI: -2.79, -0.18; -1.05, 95% CI: -2.15, 0.05, respectively]. There was no statistical evidence of interaction between the two exposures, although children with both higher isophorone exposure and a low HOME score had a decrement in math scale score beyond the additive effect of each exposure. This was primarily observed among male children. These findings suggest that aspects of both the physical and social environments are independently associated with children's early cognitive skills. Future research aiming to improve children's early cognitive skills and subsequent school readiness should address both domains.

An Autosomal Genetic Linkage Map of the Sheep Genome

PubMed Central

Crawford, A. M.; Dodds, K. G.; Ede, A. J.; Pierson, C. A.; Montgomery, G. W.; Garmonsway, H. G.; Beattie, A. E.; Davies, K.; Maddox, J. F.; Kappes, S. W.; Stone, R. T.; Nguyen, T. C.; Penty, J. M.; Lord, E. A.; Broom, J. E.; Buitkamp, J.; Schwaiger, W.; Epplen, J. T.; Matthew, P.; Matthews, M. E.; Hulme, D. J.; Beh, K. J.; McGraw, R. A.; Beattie, C. W.

1995-01-01

We report the first extensive ovine genetic linkage map covering 2070 cM of the sheep genome. The map was generated from the linkage analysis of 246 polymorphic markers, in nine three-generation fullsib pedigrees, which make up the AgResearch International Mapping Flock. We have exploited many markers from cattle so that valuable comparisons between these two ruminant linkage maps can be made. The markers, used in the segregation analyses, comprised 86 anonymous microsatellite markers derived from the sheep genome, 126 anonymous microsatellites from cattle, one from deer, and 33 polymorphic markers of various types associated with known genes. The maximum number of informative meioses within the mapping flock was 222. The average number of informative meioses per marker was 140 (range 18-209). Linkage groups have been assigned to all 26 sheep autosomes. PMID:7498748

The relationship between neutrophil to lymphocyte ratio, platelet to lymphocyte ratio and thrombolysis in myocardial infarction risk score in patients with ST elevation acute myocardial infarction before primary coronary intervention

PubMed Central

Ertaş, Faruk; Bilik, Mehmet Zihni; Akıl, Mehmet Ata; Özyurtlu, Ferhat; Aydın, Mesut; Oylumlu, Mustafa; Polat, Nihat; Yüksel, Murat; Yıldız, Abdulkadir; Kaya, Hasan; Akyüz, Abdurrahman; Ayçiçek, Hilal; Özbek, Mehmet; Toprak, Nizamettin

2015-01-01

Introduction The thrombolysis in myocardial infarction (TIMI) risk score is calculated as the sum of independent predictors of mortality and ischemic events in ST elevation acute myocardial infarction (STEMI). Several studies show that the neutrophil to lymphocyte ratio (NLR) is a prognostic inflammatory marker. In preliminary studies, platelet to lymphocyte ratio (PLR) has been proposed as a pro-thrombotic marker. The relationship between NLR, PLR and TIMI risk score for STEMI has never been studied. Aim To evaluate the association between TIMI-STEMI risk score and NLR, PLR and other biochemical indices in STEMI. Material and methods In this retrospective study, we evaluated 390 patients who presented with STEMI within 12 h of symptom onset. Patients were grouped according to low and high TIMI risk scores. Results We enrolled 390 patients (mean age 61.9 ±13.6 years; 73% were men). The NLR, platelet distribution width (PDW) and uric acid level (UA) were significantly associated with a high TIMI-STEMI risk score (p = 0.016, p = 0.008, p = 0.030, respectively), but PLR was not associated with a high TIMI-STEMI risk score. Left ventricular ejection fraction was an independent predictor of TIMI-STEMI risk score. A cut-off point of TIMI-STEMI score of > 4 predicted in-hospital mortality (sensitivity 75%, specificity 70%, p < 0.001). We found that NLR, PDW, and UA level were associated with TIMI-STEMI risk score. Conclusions Neutrophil to lymphocyte ratio, PDW and UA level are convenient, inexpensive and reproducible biomarkers for STEMI prognosis before primary angioplasty when these indicators are combined with the TIMI-STEMI risk score. We believe that these significant findings can guide further clinical practice. PMID:26161105

Efficient Generation of Marker-Free Transgenic Rice Plants Using an Improved Transposon-Mediated Transgene Reintegration Strategy1

PubMed Central

Gao, Xiaoqing; Zhou, Jie; Li, Jun; Zou, Xiaowei; Zhao, Jianhua; Li, Qingliang; Xia, Ran; Yang, Ruifang; Wang, Dekai; Zuo, Zhaoxue; Tu, Jumin; Tao, Yuezhi; Chen, Xiaoyun; Xie, Qi; Zhu, Zengrong

2015-01-01

Marker-free transgenic plants can be developed through transposon-mediated transgene reintegration, which allows intact transgene insertion with defined boundaries and requires only a few primary transformants. In this study, we improved the selection strategy and validated that the maize (Zea mays) Activator/Dissociation (Ds) transposable element can be routinely used to generate marker-free transgenic plants. A Ds-based gene of interest was linked to green fluorescent protein in transfer DNA (T-DNA), and a green fluorescent protein-aided counterselection against T-DNA was used together with polymerase chain reaction (PCR)-based positive selection for the gene of interest to screen marker-free progeny. To test the efficacy of this strategy, we cloned the Bacillus thuringiensis (Bt) δ-endotoxin gene into the Ds elements and transformed transposon vectors into rice (Oryza sativa) cultivars via Agrobacterium tumefaciens. PCR assays of the transposon empty donor site exhibited transposition in somatic cells in 60.5% to 100% of the rice transformants. Marker-free (T-DNA-free) transgenic rice plants derived from unlinked germinal transposition were obtained from the T1 generation of 26.1% of the primary transformants. Individual marker-free transgenic rice lines were subjected to thermal asymmetric interlaced-PCR to determine Ds(Bt) reintegration positions, reverse transcription-PCR and enzyme-linked immunosorbent assay to detect Bt expression levels, and bioassays to confirm resistance against the striped stem borer Chilo suppressalis. Overall, we efficiently generated marker-free transgenic plants with optimized transgene insertion and expression. The transposon-mediated marker-free platform established in this study can be used in rice and possibly in other important crops. PMID:25371551

Efficient generation of marker-free transgenic rice plants using an improved transposon-mediated transgene reintegration strategy.

PubMed

Gao, Xiaoqing; Zhou, Jie; Li, Jun; Zou, Xiaowei; Zhao, Jianhua; Li, Qingliang; Xia, Ran; Yang, Ruifang; Wang, Dekai; Zuo, Zhaoxue; Tu, Jumin; Tao, Yuezhi; Chen, Xiaoyun; Xie, Qi; Zhu, Zengrong; Qu, Shaohong

2015-01-01

Marker-free transgenic plants can be developed through transposon-mediated transgene reintegration, which allows intact transgene insertion with defined boundaries and requires only a few primary transformants. In this study, we improved the selection strategy and validated that the maize (Zea mays) Activator/Dissociation (Ds) transposable element can be routinely used to generate marker-free transgenic plants. A Ds-based gene of interest was linked to green fluorescent protein in transfer DNA (T-DNA), and a green fluorescent protein-aided counterselection against T-DNA was used together with polymerase chain reaction (PCR)-based positive selection for the gene of interest to screen marker-free progeny. To test the efficacy of this strategy, we cloned the Bacillus thuringiensis (Bt) δ-endotoxin gene into the Ds elements and transformed transposon vectors into rice (Oryza sativa) cultivars via Agrobacterium tumefaciens. PCR assays of the transposon empty donor site exhibited transposition in somatic cells in 60.5% to 100% of the rice transformants. Marker-free (T-DNA-free) transgenic rice plants derived from unlinked germinal transposition were obtained from the T1 generation of 26.1% of the primary transformants. Individual marker-free transgenic rice lines were subjected to thermal asymmetric interlaced-PCR to determine Ds(Bt) reintegration positions, reverse transcription-PCR and enzyme-linked immunosorbent assay to detect Bt expression levels, and bioassays to confirm resistance against the striped stem borer Chilo suppressalis. Overall, we efficiently generated marker-free transgenic plants with optimized transgene insertion and expression. The transposon-mediated marker-free platform established in this study can be used in rice and possibly in other important crops. © 2015 American Society of Plant Biologists. All Rights Reserved.

Bone metabolism in galactosemia.

PubMed

Panis, B; Forget, P Ph; van Kroonenburgh, M J P G; Vermeer, C; Menheere, P P; Nieman, F H; Rubio-Gozalbo, M E

2004-10-01

Classical galactosemia is an autosomal recessively inherited disorder of galactose metabolism. Treatment consists of life-long dietary restriction of galactose. Despite treatment, long-term complications occur such as a decreased bone mineral density (BMD). A decreased BMD might be the result of either dietary deficiencies secondary to the galactose-restricted diet or unknown intrinsic factors. In this study, 40 children with classical galactosemia (13 males and 27 females, aged 3-17 years) on dietary treatment were included to gain insight in the bone metabolism of galactosemics. We found weight and height Z scores significantly decreased in galactosemics. Mean areal BMD Z scores of lumbar spine and of femoral neck as measured by Dual energy X-ray Absorptiometry (DXA) were -0.6 (P < 0.001) and -0.3 (P = 0.066), respectively. Mean volumetric BMD of the femoral neck was significant lower in galactosemics (P < 0.001). The recommended dietary allowances (RDA) for calcium, magnesium, zinc, vitamin D, and protein were met in all patients. Mean serum levels of calcium, phosphate, magnesium, zinc, 1,25-dihydroxy vitamin D (1,25OHD), parathormone (PTH), 17-beta estradiol, bone alkaline phosphatase (BAP), and under-carboxylated osteocalcin (ucOC) were normal. Serum levels of IGF-1 Z score, carboxylated osteocalcin (cOC), N-terminal telopeptide (NTX), and C-terminal telopeptide (CTX) were significantly lower in galactosemics than in control subjects. The different bone markers were strongly correlated. The low levels of IGF-1 Z score, formation marker cOC, and resorption markers NTX and CTX suggest a decreased bone metabolism in galactosemics.

The association between a body shape index and cardiovascular risk in overweight and obese children and adolescents.

PubMed

Mameli, Chiara; Krakauer, Nir Y; Krakauer, Jesse C; Bosetti, Alessandra; Ferrari, Chiara Matilde; Moiana, Norma; Schneider, Laura; Borsani, Barbara; Genoni, Teresa; Zuccotti, Gianvincenzo

2018-01-01

A Body Shape Index (ABSI) and normalized hip circumference (Hip Index, HI) have been recently shown to be strong risk factors for mortality and for cardiovascular disease in adults. We conducted an observational cross-sectional study to evaluate the relationship between ABSI, HI and cardiometabolic risk factors and obesity-related comorbidities in overweight and obese children and adolescents aged 2-18 years. We performed multivariate linear and logistic regression analyses with BMI, ABSI, and HI age and sex normalized z scores as predictors to examine the association with cardiometabolic risk markers (systolic and diastolic blood pressure, fasting glucose and insulin, total cholesterol and its components, transaminases, fat mass % detected by bioelectrical impedance analysis) and obesity-related conditions (including hepatic steatosis and metabolic syndrome). We recruited 217 patients (114 males), mean age 11.3 years. Multivariate linear regression showed a significant association of ABSI z score with 10 out of 15 risk markers expressed as continuous variables, while BMI z score showed a significant correlation with 9 and HI only with 1. In multivariate logistic regression to predict occurrence of obesity-related conditions and above-threshold values of risk factors, BMI z score was significantly correlated to 7 out of 12, ABSI to 5, and HI to 1. Overall, ABSI is an independent anthropometric index that was significantly associated with cardiometabolic risk markers in a pediatric population affected by overweight and obesity.

Correlation of serum liver fibrosis markers with severity of liver dysfunction in liver cirrhosis: a retrospective cross-sectional study

PubMed Central

Zhu, Cuihong; Qi, Xingshun; Li, Hongyu; Peng, Ying; Dai, Junna; Chen, Jiang; Xia, Chunlian; Hou, Yue; Zhang, Wenwen; Guo, Xiaozhong

2015-01-01

Hyaluronic acid (HA), laminin (LN), amino-terminal pro-peptide of type III pro-collagen (PIIINP), and collagen IV (CIV) are four major serum markers of liver fibrosis. This retrospective cross-sectional study aimed to evaluate the correlations of the four serum markers with the severity of liver dysfunction in cirrhotic patients. Between January 2013 and June 2014, a total of 228 patients with a clinical diagnosis with liver cirrhosis and without malignancy underwent the tests of HA, LN, PIIINP, and CIV levels. Laboratory data were collected. Child-Pugh and model for the end-stage of liver diseases (MELD) scores were calculated. Of them, 32%, 40%, and 18% had Child-Pugh class A, B, and C, respectively. MELD score was 7.58±0.50. HA (coefficient r: 0.1612, P=0.0203), LN (coefficient r: 0.2445, P=0.0004), and CIV (coefficient r: 0.2361, P=0.0006) levels significantly correlated with Child-Pugh score, but not PIIINP level. Additionally, LN (coefficient r: 0.2588, P=0.0002) and CIV (coefficient r: 0.1795, P=0.0108) levels significantly correlated with MELD score, but not HA or PIIINP level. In conclusions, HA, LN, and CIV levels might be positively associated with the severity of liver dysfunction in cirrhotic patients. However, given a relatively weak correlation between them, our findings should be cautiously interpreted and further validated. PMID:26131195

[Linkage analysis of susceptibility loci in 2 target chromosomes in pedigrees with paranoid schizophrenia and undifferentiated schizophrenia].

PubMed

Zeng, Li-ping; Hu, Zheng-mao; Mu, Li-li; Mei, Gui-sen; Lu, Xiu-ling; Zheng, Yong-jun; Li, Pei-jian; Zhang, Ying-xue; Pan, Qian; Long, Zhi-gao; Dai, He-ping; Zhang, Zhuo-hua; Xia, Jia-hui; Zhao, Jing-ping; Xia, Kun

2011-06-01

To investigate the relationship of susceptibility loci in chromosomes 1q21-25 and 6p21-25 and schizophrenia subtypes in Chinese population. A genomic scan and parametric and non-parametric analyses were performed on 242 individuals from 36 schizophrenia pedigrees, including 19 paranoid schizophrenia and 17 undifferentiated schizophrenia pedigrees, from Henan province of China using 5 microsatellite markers in the chromosome region 1q21-25 and 8 microsatellite markers in the chromosome region 6p21-25, which were the candidates of previous studies. All affected subjects were diagnosed and typed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revised (DSM-IV-TR; American Psychiatric Association, 2000). All subjects signed informed consent. In chromosome 1, parametric analysis under the dominant inheritance mode of all 36 pedigrees showed that the maximum multi-point heterogeneity Log of odds score method (HLOD) score was 1.33 (α = 0.38). The non-parametric analysis and the single point and multi-point nonparametric linkage (NPL) scores suggested linkage at D1S484, D1S2878, and D1S196. In the 19 paranoid schizophrenias pedigrees, linkage was not observed for any of the 5 markers. In the 17 undifferentiated schizophrenia pedigrees, the multi-point NPL score was 1.60 (P= 0.0367) at D1S484. The single point NPL score was 1.95(P= 0.0145) and the multi-point NPL score was 2.39 (P= 0.0041) at D1S2878. Additionally, the multi-point NPL score was 1.74 (P= 0.0255) at D1S196. These same three loci showed suggestive linkage during the integrative analysis of all 36 pedigrees. In chromosome 6, parametric linkage analysis under the dominant and recessive inheritance and the non-parametric linkage analysis of all 36 pedigrees and the 17 undifferentiated schizophrenia pedigrees, linkage was not observed for any of the 8 markers. In the 19 paranoid schizophrenias pedigrees, parametric analysis showed that under recessive inheritance mode the maximum single-point HLOD score was 1.26 (α = 0.40) and the multi-point HLOD was 1.12 (α = 0.38) at D6S289 in the chromosome 6p23. In nonparametric analysis, the single-point NPL score was 1.52 (P= 0.0402) and the multi-point NPL score was 1.92 (P= 0.0206) at D6S289. Susceptibility genes correlated with undifferentiated schizophrenia pedigrees from D1S484, D1S2878, D1S196 loci, and those correlated with paranoid schizophrenia pedigrees from D6S289 locus are likely present in chromosome regions 1q23.3 and 1q24.2, and chromosome region 6p23, respectively.

Predictive value of [-2]propsa (p2psa) and its derivatives for the prostate cancer detection in the 2.0 to 10.0ng/mL PSA range.

PubMed

Vukovic, I; Djordjevic, D; Bojanic, N; Babic, U; Soldatovic, I

2017-01-01

To assess predictive value of new tumor markers, precursor of prostate specific antigen (p2PSA) and its derivates-%p2PSA and prostate health index (PHI) in detection of patients with indolent and aggressive prostate cancer (PC) in a subcohort of man whose total PSA ranged from 2 to 10ng/mL. This cross-sectional study included 129 consecutive male patients aged over 50 years, with no previous history of PC and with normal digital rectal examination findings, but with serum PSA in interval between 2 and 10ng/mL. All patients underwent standard transrectal ultrasonography guided prostate biopsy for the first time. For all patients, serum PSA, free PSA (fPSA) and p2PSA were measured and PHI and %p2PSA were calculated. PHI and %p2PSA levels were significanlty higher in patients with PC compared to those without this malignancy. The same findings have been observed in group of patients with Gleason score ≥7 compared to those with Gleason score <7. ROC analysis reveled the highest area under the curve with these two markers. Multivariate logistic regression showed significant improvement in PC detection and its agressive form (assumed as Gleason score ≥7). New markers, derivates of p2PSA (especially %p2PSA and PHI), represente potentially very important clinical tool for predicting presence of PC, and even more important, to discriminate patients with Gleason score <7 from those with Gleason score ≥7 with total PSA in range from 2 to 10ng/mL. Copyright® by the International Brazilian Journal of Urology.

Quantification of protein expression in cells and cellular subcompartments on immunohistochemical sections using a computer supported image analysis system.

PubMed

Braun, Martin; Kirsten, Robert; Rupp, Niels J; Moch, Holger; Fend, Falko; Wernert, Nicolas; Kristiansen, Glen; Perner, Sven

2013-05-01

Quantification of protein expression based on immunohistochemistry (IHC) is an important step for translational research and clinical routine. Several manual ('eyeballing') scoring systems are used in order to semi-quantify protein expression based on chromogenic intensities and distribution patterns. However, manual scoring systems are time-consuming and subject to significant intra- and interobserver variability. The aim of our study was to explore, whether new image analysis software proves to be sufficient as an alternative tool to quantify protein expression. For IHC experiments, one nucleus specific marker (i.e., ERG antibody), one cytoplasmic specific marker (i.e., SLC45A3 antibody), and one marker expressed in both compartments (i.e., TMPRSS2 antibody) were chosen. Stainings were applied on TMAs, containing tumor material of 630 prostate cancer patients. A pathologist visually quantified all IHC stainings in a blinded manner, applying a four-step scoring system. For digital quantification, image analysis software (Tissue Studio v.2.1, Definiens AG, Munich, Germany) was applied to obtain a continuous spectrum of average staining intensity. For each of the three antibodies we found a strong correlation of the manual protein expression score and the score of the image analysis software. Spearman's rank correlation coefficient was 0.94, 0.92, and 0.90 for ERG, SLC45A3, and TMPRSS2, respectively (p⟨0.01). Our data suggest that the image analysis software Tissue Studio is a powerful tool for quantification of protein expression in IHC stainings. Further, since the digital analysis is precise and reproducible, computer supported protein quantification might help to overcome intra- and interobserver variability and increase objectivity of IHC based protein assessment.

The prognostic value of the systemic inflammatory score in patients with unresectable metastatic colorectal cancer.

PubMed

Shibutani, Masatsune; Maeda, Kiyoshi; Nagahara, Hisashi; Fukuoka, Tatsunari; Matsutani, Shinji; Kimura, Kenjiro; Amano, Ryosuke; Hirakawa, Kosei; Ohira, Masaichi

2018-07-01

Inflammation has been widely recognized as a contributor to cancer progression and several inflammatory markers have been reported as associated with the clinical outcomes in patients with various types of cancer. Recently, a novel inflammatory marker, the systemic inflammatory score (SIS), which is based on a combination of the lymphocyte-to-monocyte ratio (LMR) and the serum albumin concentration has been reported as a useful prognostic marker. The aim of the present study was to assess the prognostic value of the SIS in patients with unresectable metastatic colorectal cancer (mCRC). The retrospective cohort study included 160 patients who underwent combination chemotherapy for unresectable mCRC between January 2008 and December 2016. The SIS was used to classify the patients into three groups based on their LMR and the serum albumin concentration. Patients with high-LMR and high serum albumin level were given a score of 0; patients with low-LMR or low serum albumin level were given a score of 1; patients with low-LMR and low serum albumin level were given a score of 2. There were significant differences in the overall survival among the three SIS groups and the SIS was an independent prognostic factor for the overall survival. Although the SIS was significantly associated with the overall survival rate even when using the original cut-off values, the SIS according to the new cut-off values had a more accurate prognostic value. The present study determined that the SIS was a useful biomarker for predicting the survival outcomes in patients with unresectable mCRC, although the optimum cut-off value of the SIS according to the patients' background needs to be examined in further studies.

Development of Serum Marker Models to Increase Diagnostic Accuracy of Advanced Fibrosis in Nonalcoholic Fatty Liver Disease: The New LINKI Algorithm Compared with Established Algorithms.

PubMed

Lykiardopoulos, Byron; Hagström, Hannes; Fredrikson, Mats; Ignatova, Simone; Stål, Per; Hultcrantz, Rolf; Ekstedt, Mattias; Kechagias, Stergios

2016-01-01

Detection of advanced fibrosis (F3-F4) in nonalcoholic fatty liver disease (NAFLD) is important for ascertaining prognosis. Serum markers have been proposed as alternatives to biopsy. We attempted to develop a novel algorithm for detection of advanced fibrosis based on a more efficient combination of serological markers and to compare this with established algorithms. We included 158 patients with biopsy-proven NAFLD. Of these, 38 had advanced fibrosis. The following fibrosis algorithms were calculated: NAFLD fibrosis score, BARD, NIKEI, NASH-CRN regression score, APRI, FIB-4, King´s score, GUCI, Lok index, Forns score, and ELF. Study population was randomly divided in a training and a validation group. A multiple logistic regression analysis using bootstrapping methods was applied to the training group. Among many variables analyzed age, fasting glucose, hyaluronic acid and AST were included, and a model (LINKI-1) for predicting advanced fibrosis was created. Moreover, these variables were combined with platelet count in a mathematical way exaggerating the opposing effects, and alternative models (LINKI-2) were also created. Models were compared using area under the receiver operator characteristic curves (AUROC). Of established algorithms FIB-4 and King´s score had the best diagnostic accuracy with AUROCs 0.84 and 0.83, respectively. Higher accuracy was achieved with the novel LINKI algorithms. AUROCs in the total cohort for LINKI-1 was 0.91 and for LINKI-2 models 0.89. The LINKI algorithms for detection of advanced fibrosis in NAFLD showed better accuracy than established algorithms and should be validated in further studies including larger cohorts.

Imputation of unordered markers and the impact on genomic selection accuracy

USDA-ARS?s Scientific Manuscript database

Genomic selection, a breeding method that promises to accelerate rates of genetic gain, requires dense, genome-wide marker data. Genotyping-by-sequencing can generate a large number of de novo markers. However, without a reference genome, these markers are unordered and typically have a large propo...

Epithelial expression of extracellular matrix metalloproteinase inducer/CD147 and matrix metalloproteinase-2 in neoplasms and precursor lesions derived from cutaneous squamous cells: An immunohistochemical study.

PubMed

Ayva, Sebnem Kupana; Karabulut, Ayse Anil; Akatli, Ayşe Nur; Atasoy, Pinar; Bozdogan, Onder

2013-10-01

Extracellular matrix metalloproteinase inducer (CD147) is a transmembrane glycoprotein involved in the regulation of matrix metalloproteinases (MMPs). The study investigated CD147 and MMP-2 expression in epidermis of cutaneous squamous lesions. CD147 and MMP-2 expressions were evaluated immunohistochemically in 44 specimens: 18 actinic keratoses (AK), 6 squamous cell carcinomas in situ (SCCIS), 13 squamous cell carcinomas (SCC; peritumoral and invasive portions assessed), and 7 normal skins. Patterns of expression were assessed, with MMP-2 in nuclei (MMP-2n) and cytoplasm (MMP-2c) evaluated separately. The expression of each marker was quantified using a calculated immunohistochemical/histologic score (H-score). Correlations were analyzed for the marker H-scores in each study group. Associations between H-scores and histopathologic parameters were also evaluated. CD147 H-score was the highest in SCC (invasive islands), followed by AK, SCCIS, and control specimens, respectively. MMP-2n and MMP-2c H-scores were the highest in AK, followed by SCCIS, SCC, and control specimens, respectively. MMP-2c and MMP-2n H-scores were significantly higher in peritumoral epidermis than in invasive islands of SCC. MMP-2c and CD147 H-scores were positively correlated in the peritumoral SCCs. CD147 H-score was positively correlated with tumor differentiation in SCC. The findings suggest that overexpression of CD147 plays a role in the development of SCC. Copyright © 2013 Elsevier GmbH. All rights reserved.

Easy calculations of lod scores and genetic risks on small computers.

PubMed Central

Lathrop, G M; Lalouel, J M

1984-01-01

A computer program that calculates lod scores and genetic risks for a wide variety of both qualitative and quantitative genetic traits is discussed. An illustration is given of the joint use of a genetic marker, affection status, and quantitative information in counseling situations regarding Duchenne muscular dystrophy. PMID:6585139

Assessment of the value of a genetic risk score in improving the estimation of coronary risk

USDA-ARS?s Scientific Manuscript database

The American Heart Association has established criteria for the evaluation of novel markers of cardiovascular risk. In accordance with these criteria, we assessed the association between a multi-locus genetic risk score (GRS) and incident coronary heart disease (CHD), and evaluated whether this GRS ...

The Anatomy Competence Score--A New Marker for Anatomical Ability

ERIC Educational Resources Information Center

Schoeman, Scarpa; Chandratilake, Madawa

2012-01-01

The assessment of students' ability in gross anatomy is a complex process as it involves the measurement of multiple facets. In this work, the authors developed and introduced the Anatomy Competence Score (ACS), which incorporates the three domains of anatomy teaching and assessment namely: theoretical knowledge, practical 3D application of the…

Child maltreatment and household dysfunction: associations with pubertal development in a British birth cohort

PubMed Central

Li, Leah; Denholm, Rachel; Power, Chris

2014-01-01

Background: We aimed to establish the association between adverse childhood experiences (maltreatment and household dysfunction) and pubertal maturation, which is associated with later health outcome(s). Methods: The 1958 British birth cohort (n = 17 638) includes all born in one week, March 1958, followed up to mid adulthood. Pubertal stage was rated by medical personnel at 11 and 16 years of age (y). Childhood maltreatment (neglect or abuse) and household dysfunction scores were constructed from information ascertained in childhood and at 45 y. Results: Childhood neglect, assessed at 7 y, was associated with late pubertal development on several markers after adjusting for early life circumstances: relative risk ratio (RRRadjusted) was 1.13 (95% CI: 1.06,1.21) and 1.06 (1.00,1.12) for late menarche and breast development (females) per unit increase in neglect score ranging 0–7, respectively; 1.14 (1.08,1.20) for late voice change and 1.07 (1.02,1.13) for pubic hair growth (males). The RRRadjusted for late pubic hair (females) and genitalia and facial hair (males) development was 1.04 (P = 0.052 to 0.085). Abuse score (0–3, for physical, sexual or psychological abuse) was associated in females with late menarche [RRRadjusted = 1.17 (1.01,1.36)] and in males with late pubic hair growth [RRRadjusted = 1.16 (1.01,1.34)] per unit increase, but not with other pubertal markers. Neither score (neglect or abuse) was associated with early puberty, but sexual abuse was associated with early [RRRadjusted = 1.86 (1.06,3.29)] as well as late menarche [RRRadjusted = 1.66 (1.02,2.71)] and witnessing abuse with early genitalia development [RRRadjusted = 1.57 (1.02,2.41)]. Household dysfunction score was not associated consistently with pubertal markers. Conclusions: Cumulative neglect by 7 y was associated with delayed development of several pubertal markers. The underlying role of pubertal development in linking childhood neglect with future adult health warrants further consideration. PMID:24706731

Correlation between Apgar score and urinary uric acid to creatinine ratio in perinatal asphyxia.

PubMed

Basu, Pallab; Som, Sabyasachi; Choudhuri, Nabendu; Das, Harendranath

2008-10-01

A randomized case control hospital based study was conducted over 12 months time on 31 asphyxiated and 31 normal newborn to see whether urinary uric acid can be used as a marker of perinatal asphyxia and can be correlated with the clinical diagnosis by Apgar score. Uric acid and creatinine were estimated in spot urine within 24 hours after birth in both cases and controls. A ratio between concentrations of uric acid to creatinine was estimated and compared between cases and controls. It was found that the ratios were significantly higher in cases than controls (3.1± 1.3 vs 0.96± 0.54; P < 0.001) and among asphyxia patients, a significant negative linear correlation was found between the uric acid to creatinine ratio and the Apgar score (r = -0.857, P < 0.001). So urinary uric acid to creatinine ratio can be used as an additional non-invasive dispace, easy and at the same time early biochemical marker of birth asphyxia which biochemically supports the clinical diagnosis and severity grading of asphyxia by Apgar score.

Minefield reconnaissance and detector system

DOEpatents

Butler, Millard T.; Cave, Steven P.; Creager, James D.; Johnson, Charles M.; Mathes, John B.; Smith, Kirk J.

1994-01-01

A multi-sensor system (10) for detecting the presence of objects on the surface of the ground or buried just under the surface, such as anti-personnel or anti-tank mines or the like. A remote sensor platform (12) has a plurality of metal detector sensors (22) and a plurality of short pulse radar sensors (24). The remote sensor platform (12) is remotely controlled from a processing and control unit (14) and signals from the remote sensor platform (12) are sent to the processing and control unit (14) where they are individually evaluated in separate data analysis subprocess steps (34, 36) to obtain a probability "score" for each of the pluralities of sensors (22, 24). These probability scores are combined in a fusion subprocess step (38) by comparing score sets to a probability table (130) which is derived based upon the historical incidence of object present conditions given that score set. A decision making rule is applied to provide an output which is optionally provided to a marker subprocess (40) for controlling a marker device (76) to mark the location of found objects.

Moving metal artifact reduction in cone-beam CT scans with implanted cylindrical gold markers

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

Toftegaard, Jakob, E-mail: jaktofte@rm.dk; Fledelius, Walther; Worm, Esben S.

2014-12-15

Purpose: Implanted gold markers for image-guided radiotherapy lead to streaking artifacts in cone-beam CT (CBCT) scans. Several methods for metal artifact reduction (MAR) have been published, but they all fail in scans with large motion. Here the authors propose and investigate a method for automatic moving metal artifact reduction (MMAR) in CBCT scans with cylindrical gold markers. Methods: The MMAR CBCT reconstruction method has six steps. (1) Automatic segmentation of the cylindrical markers in the CBCT projections. (2) Removal of each marker in the projections by replacing the pixels within a masked area with interpolated values. (3) Reconstruction of amore » marker-free CBCT volume from the manipulated CBCT projections. (4) Reconstruction of a standard CBCT volume with metal artifacts from the original CBCT projections. (5) Estimation of the three-dimensional (3D) trajectory during CBCT acquisition for each marker based on the segmentation in Step 1, and identification of the smallest ellipsoidal volume that encompasses 95% of the visited 3D positions. (6) Generation of the final MMAR CBCT reconstruction from the marker-free CBCT volume of Step 3 by replacing the voxels in the 95% ellipsoid with the corresponding voxels of the standard CBCT volume of Step 4. The MMAR reconstruction was performed retrospectively using a half-fan CBCT scan for 29 consecutive stereotactic body radiation therapy patients with 2–3 gold markers implanted in the liver. The metal artifacts of the MMAR reconstructions were scored and compared with a standard MAR reconstruction by counting the streaks and by calculating the standard deviation of the Hounsfield units in a region around each marker. Results: The markers were found with the same autosegmentation settings in 27 CBCT scans, while two scans needed slightly changed settings to find all markers automatically in Step 1 of the MMAR method. MMAR resulted in 15 scans with no streaking artifacts, 11 scans with 1–4 streaks, and 3 scans with severe streaking artifacts. The corresponding numbers for MAR were 8 (no streaks), 1 (1–4 streaks), and 20 (severe streaking artifacts). The MMAR method was superior to MAR in scans with more than 8 mm 3D marker motion and comparable to MAR for scans with less than 8 mm motion. In addition, the MMAR method was tested on a 4D CBCT reconstruction for which it worked equally well as for the 3D case. The markers in the 4D case had very low motion blur. Conclusions: An automatic method for MMAR in CBCT scans was proposed and shown to effectively remove almost all streaking artifacts in a large set of clinical CBCT scans with implanted gold markers in the liver. Residual streaking artifacts observed in three CBCT scans may be removed with better marker segmentation.« less

Rapid development of molecular markers by next-generation sequencing linked to a gene conferring phomopsis stem blight disease resistance for marker-assisted selection in lupin (Lupinus angustifolius L.) breeding.

PubMed

Yang, Huaan; Tao, Ye; Zheng, Zequn; Shao, Di; Li, Zhenzhong; Sweetingham, Mark W; Buirchell, Bevan J; Li, Chengdao

2013-02-01

Selection for phomopsis stem blight disease (PSB) resistance is one of the key objectives in lupin (Lupinus angustifolius L.) breeding programs. A cross was made between cultivar Tanjil (resistant to PSB) and Unicrop (susceptible). The progeny was advanced into F(8) recombinant inbred lines (RILs). The RIL population was phenotyped for PSB disease resistance. Twenty plants from the RIL population representing disease resistance and susceptibility was subjected to next-generation sequencing (NGS)-based restriction site-associated DNA sequencing on the NGS platform Solexa HiSeq2000, which generated 7,241 single nucleotide polymorphisms (SNPs). Thirty-three SNP markers showed the correlation between the marker genotypes and the PSB disease phenotype on the 20 representative plants, which were considered as candidate markers linked to a putative R gene for PSB resistance. Seven candidate markers were converted into sequence-specific PCR markers, which were designated as PhtjM1, PhtjM2, PhtjM3, PhtjM4, PhtjM5, PhtjM6 and PhtjM7. Linkage analysis of the disease phenotyping data and marker genotyping data on a F(8) population containing 187 RILs confirmed that all the seven converted markers were associated with the putative R gene within the genetic distance of 2.1 CentiMorgan (cM). One of the PCR markers, PhtjM3, co-segregated with the R gene. The seven established PCR markers were tested in the 26 historical and current commercial cultivars released in Australia. The numbers of "false positives" (showing the resistance marker allele band but lack of the putative R gene) for each of the seven PCR markers ranged from nil to eight. Markers PhtjM4 and PhtjM7 are recommended in marker-assisted selection for PSB resistance in the Australian national lupin breeding program due to its wide applicability on breeding germplasm and close linkage to the putative R gene. The results demonstrated that application of NGS technology is a rapid and cost-effective approach in development of markers for molecular plant breeding.

A novel mutation of PAX3 in a Chinese family with Waardenburg syndrome.

PubMed

Qin, Wei; Shu, Anli; Qian, Xueqing; Gao, Jianjun; Xing, Qinghe; Zhang, Juan; Zheng, Yonglan; Li, Xingwang; Li, Sheng; Feng, Guoyin; He, Lin

2006-08-28

The molecular characterization of 34 members of a Chinese family, with 22 members in four generations, affected with Waardenburg syndrome (WS1). A detailed family history and clinical data were collected. A genome-wide scan by two-point linkage analysis using more than 400 microsatellite markers in combination with haplotype analysis was performed. Mutation screening was carried out in the candidate gene by sequencing of amplified products. A maximum two-point lod score of 6.53 at theta = 0.00 was obtained with marker D2S2248. Haplotype analysis placed the WS1 locus to a 45.74 cM region between D2S117 and D2S206, in close proximity to the PAX3 gene on chromosome 2q35. Mutation screening in PAX3 identified a 701T > C mutation which converted a highly conserved Leu to Pro. This nucleotide alteration was neither seen in unaffected members of the family nor found in 50 unrelated control subjects. The present study identified a novel 701T > C mutation in PAX3. The mutation observed in this family highlights the phenotypic heterogeneity of the disorder.

Molecular Linkage Mapping and Marker-Trait Associations with NlRPT, a Downy Mildew Resistance Gene in Nicotiana langsdorffii

PubMed Central

Zhang, Shouan; Gao, Muqiang; Zaitlin, David

2012-01-01

Nicotiana langsdorffii is one of two species of Nicotiana known to express an incompatible interaction with the oomycete Peronospora tabacina, the causal agent of tobacco blue mold disease. We previously showed that incompatibility is due to the hypersensitive response (HR), and plants expressing the HR are resistant to P. tabacina at all stages of growth. Resistance is due to a single dominant gene in N. langsdorffii accession S-4-4 that we have named NlRPT. In further characterizing this unique host-pathogen interaction, NlRPT has been placed on a preliminary genetic map of the N. langsdorffii genome. Allelic scores for five classes of DNA markers were determined for 90 progeny of a “modified backcross” involving two N. langsdorffii inbred lines and the related species N. forgetiana. All markers had an expected segregation ratio of 1:1, and were scored in a common format. The map was constructed with JoinMap 3.0, and loci showing excessive transmission distortion were removed. The linkage map consists of 266 molecular marker loci defined by 217 amplified fragment length polymorphisms (AFLPs), 26 simple-sequence repeats (SSRs), 10 conserved orthologous sequence markers, nine inter-simple sequence repeat markers, and four target region amplification polymorphism markers arranged in 12 linkage groups with a combined length of 1062 cM. NlRPT is located on linkage group three, flanked by four AFLP markers and one SSR. Regions of skewed segregation were detected on LGs 1, 5, and 9. Markers developed for N. langsdorffii are potentially useful genetic tools for other species in Nicotiana section Alatae, as well as in N. benthamiana. We also investigated whether AFLPs could be used to infer genetic relationships within N. langsdorffii and related species from section Alatae. A phenetic analysis of the AFLP data showed that there are two main lineages within N. langsdorffii, and that both contain populations expressing dominant resistance to P. tabacina. PMID:22936937

Kinetics and Mechanism of Chemical Marker Formation and Water-Activated Heat Generation

DTIC Science & Technology

1994-05-01

activated chemical heaters. It has recently been discovered at the Army’s Natick, Massachusetts Research, Development & Engineering Center that certain...FUNDING NUMBERS 0 i Kinetics and Mechanism of Chemical Marker Formation and Water-Activated Heat Generation ~~ 3 6. AUTHOR(S) I-GZ05 Kenneth Kustin DI N...unlimited. rpIC Q.UA y uI sECTED 5 13. ABSTRACT (Maximum 200 words) n Research has been conducted on two projects: intrinsic chemical markers and water

An autosomal genetic linkage map of the sheep genome

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

Crawford, A.M.; Ede, A.J.; Pierson, C.A.

1995-06-01

We report the first extensive ovine genetic linkage map covering 2070 cM of the sheep genome. The map was generated from the linkage analysis of 246 polymorphic markers, in nine three-generation full-sib pedigrees, which make up the AgResearch International Mapping Flock. We have exploited many markers from cattle so that valuable comparisons between these two ruminant linkage maps can be made. The markers, used in the segregation analyses, comprised 86 anonymous microsatellite markers derived from the sheep genome, 126 anonymous microsatellites from cattle, one from deer, and 33 polymorphic markers of various types associated with known genes. The maximum numbermore » of informative meioses within the mapping flock was 22. The average number of informative meioses per marker was 140 (range 18-209). Linkage groups have been assigned to all 26 sheep autosomes. 102 refs., 8 figs., 5 tabs.« less

Map refinement of locus RP13 to human chromosome 17p13.3 in a second family with autosomal dominant retinitis pigmentosa

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

Kojis, T.L.; Heinzmann, C.; Ngo, J.T.

1996-02-01

In order to elucidate the genetic basis of autosomal dominant retinitis pigmentosa (adRP) in a large eight-generation family (UCLA-RP09) of British descent, we assessed linkage between the UCLA-RP09 adRP gene and numerous genetic loci, including eight adRP candidate genes, five anonymous adRP-linked DNA loci, and 20 phenotypic markers. Linkage to the UCLA-RP09 disease gene was excluded for all eight candidate genes analyzed, including rhodopsin (RP4) and peripherin/RDS (RP7), for the four adRP loci RP1, RP9, RP10 and RP11, as well as for 17 phenotypic markers. The anonymous DNA marker locus D17S938, linked to adRP locus RP13 on chromosome 17p13.1, yieldedmore » a suggestive but not statistically significant positive lod score. Linkage was confirmed between the UCLA-RP09 adRP gene and markers distal to D17S938 in the chromosomal region 17p13.3. A reanalysis of the original RP13 data from a South African adRP family of British descent, in conjunction with our UCLA-RP09 data, suggests that only one adRP locus exists on 17p but that it maps to a more telomeric position, at band 17p13.3, than previously reported. Confirmation of the involvement of RP13 in two presumably unrelated adRP families, both of British descent, suggests that this locus is a distinct adRP gene in a proportion of British, and possibly other, adRP families. 39 refs., 4 figs., 3 tabs.« less

Assessment of genetic diversity and relationships among Egyptian mango (Mangifera indica L.) cultivers grown in Suez Canal and Sinai region using RAPD markers.

PubMed

Mansour, Hassan; Mekki, Laila E; Hussein, Mohammed A

2014-01-01

DNA-based RAPD (Random Amplification of Polymorphic DNA) markers have been used extensively to study genetic diversity and relationships in a number of fruit crops. In this study, 10 (7 commercial mango cultivars and 3 accessions) mango genotypes traditionally grown in Suez Canal and Sinai region of Egypt, were selected to assess genetic diversity and relatedness. Total genomic DNA was extracted and subjected to RAPD analysis using 30 arbitrary 10-mer primers. Of these, eleven primers were selected which gave 92 clear and bright fragments. A total of 72 polymorphic RAPD bands were detected out of 92 bands, generating 78% polymorphisms. The mean PIC values scores for all loci were of 0.85. This reflects a high level of discriminatory power of a marker and most of these primers produced unique band pattern for each cultivar. A dendrogram based on Nei's Genetic distance co-efficient implied a moderate degree of genetic diversity among the cultivars used for experimentation, with some differences. The hybrid which had derived from cultivar as female parent was placed together. In the cluster, the cultivars and accessions formed separate groups according to bearing habit and type of embryo and the members in each group were very closely linked. Cluster analysis clearly showed two main groups, the first consisting of indigenous to the Delta of Egypt cultivars and the second consisting of indigenous to the Suez Canal and Sinai region. From the analysis of results, it appears the majority of mango cultivars originated from a local mango genepool and were domesticated later. The results indicated the potential of RAPD markers for the identification and management of mango germplasm for breeding purposes.

SU-E-J-42: Evaluation of Fiducial Markers for Ultrasound and X-Ray Images Used for Motion Tracking in Pancreas SBRT

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

Ng, SK; Armour, E; Su, L

Purpose Ultrasound tracking of target motion relies on visibility of vascular and/or anatomical landmark. However this is challenging when the target is located far from vascular structures or in organs that lack ultrasound landmark structure, such as in the case of pancreas cancer. The purpose of this study is to evaluate visibility, artifacts and distortions of fusion coils and solid gold markers in ultrasound, CT, CBCT and kV images to identify markers suitable for real-time ultrasound tracking of tumor motion in SBRT pancreas treatment. Methods Two fusion coils (1mm × 5mm and 1mm × 10 mm) and a solid goldmore » marker (0.8mm × 10mm) were embedded in a tissue–like ultrasound phantom. The phantom (5cm × 12cm × 20cm) was prepared using water, gelatin and psyllium-hydrophilic-mucilloid fiber. Psylliumhydrophilic mucilloid acts as scattering medium to produce echo texture that simulates sonographic appearance of human tissue in ultrasound images while maintaining electron density close to that of water in CT images. Ultrasound images were acquired using 3D-ultrasound system with markers embedded at 5, 10 and 15mm depth from phantom surface. CT images were acquired using Philips Big Bore CT while CBCT and kV images were acquired with XVI-system (Elexta). Visual analysis was performed to compare visibility of the markers and visibility score (1 to 3) were assigned. Results All markers embedded at various depths are clearly visible (score of 3) in ultrasound images. Good visibility of all markers is observed in CT, CBCT and kV images. The degree of artifact produced by the markers in CT and CBCT images are indistinguishable. No distortion is observed in images from any modalities. Conclusion All markers are visible in images across all modalities in this homogenous tissue-like phantom. Human subject data is necessary to confirm the marker type suitable for real-time ultrasound tracking of tumor motion in SBRT pancreas treatment.« less

Lessons from mouse chimaera experiments with a reiterated transgene marker: revised marker criteria and a review of chimaera markers.

PubMed

Keighren, Margaret A; Flockhart, Jean; Hodson, Benjamin A; Shen, Guan-Yi; Birtley, James R; Notarnicola-Harwood, Antonio; West, John D

2015-08-01

Recent reports of a new generation of ubiquitous transgenic chimaera markers prompted us to consider the criteria used to evaluate new chimaera markers and develop more objective assessment methods. To investigate this experimentally we used several series of fetal and adult chimaeras, carrying an older, multi-copy transgenic marker. We used two additional independent markers and objective, quantitative criteria for cell selection and cell mixing to investigate quantitative and spatial aspects of developmental neutrality. We also suggest how the quantitative analysis we used could be simplified for future use with other markers. As a result, we recommend a five-step procedure for investigators to evaluate new chimaera markers based partly on criteria proposed previously but with a greater emphasis on examining the developmental neutrality of prospective new markers. These five steps comprise (1) review of published information, (2) evaluation of marker detection, (3) genetic crosses to check for effects on viability and growth, (4) comparisons of chimaeras with and without the marker and (5) analysis of chimaeras with both cell populations labelled. Finally, we review a number of different chimaera markers and evaluate them using the extended set of criteria. These comparisons indicate that, although the new generation of ubiquitous fluorescent markers are the best of those currently available and fulfil most of the criteria required of a chimaera marker, further work is required to determine whether they are developmentally neutral.

Targeted next generation sequencing for the detection of ciprofloxacin resistance markers using molecular inversion probes

DTIC Science & Technology

2016-07-06

1 Targeted next-generation sequencing for the detection of ciprofloxacin resistance markers using molecular inversion probes Christopher P...development and evaluation of a panel of 44 single-stranded molecular inversion probes (MIPs) coupled to next-generation sequencing (NGS) for the...padlock and molecular inversion probes as upfront enrichment steps for use with NGS showed the specificity and multiplexability of these techniques

Using Next Generation Sequencing for Multiplexed Trait-Linked Markers in Wheat

PubMed Central

Bernardo, Amy; Wang, Shan; St. Amand, Paul; Bai, Guihua

2015-01-01

With the advent of next generation sequencing (NGS) technologies, single nucleotide polymorphisms (SNPs) have become the major type of marker for genotyping in many crops. However, the availability of SNP markers for important traits of bread wheat ( Triticum aestivum L.) that can be effectively used in marker-assisted selection (MAS) is still limited and SNP assays for MAS are usually uniplex. A shift from uniplex to multiplex assays will allow the simultaneous analysis of multiple markers and increase MAS efficiency. We designed 33 locus-specific markers from SNP or indel-based marker sequences that linked to 20 different quantitative trait loci (QTL) or genes of agronomic importance in wheat and analyzed the amplicon sequences using an Ion Torrent Proton Sequencer and a custom allele detection pipeline to determine the genotypes of 24 selected germplasm accessions. Among the 33 markers, 27 were successfully multiplexed and 23 had 100% SNP call rates. Results from analysis of "kompetitive allele-specific PCR" (KASP) and sequence tagged site (STS) markers developed from the same loci fully verified the genotype calls of 23 markers. The NGS-based multiplexed assay developed in this study is suitable for rapid and high-throughput screening of SNPs and some indel-based markers in wheat. PMID:26625271

Effects of stress on emotional memory in patients with Alzheimer's disease and in healthy elderly.

PubMed

Gómez-Gallego, María; Gómez-García, Juan

2017-12-14

We aimed at examining the relation between stress markers (cortisol levels and state anxiety) with memory for emotional information in AD patients and in healthy elderly. Baseline and changes in stress markers during memory testing were assessed in a sample of 98 elderly (46 mild-to-moderate Alzheimer's disease patients and 52 controls) recruited from dementia day centers and adult day centers, respectively. Salivary cortisol, state anxiety, and measures of immediate recall and delayed recognition using the International Affective Pictures System. Patients' performance in memory tasks was not associated with either cortisol levels or anxiety. In controls, quadratic and linear associations were found between cortisol and immediate recall scores (total and bias, respectively). Besides, quadratic and linear associations were observed between anxiety and delayed recognition scores (total and bias, respectively). The emotional memory of patients with Alzheimer´s disease is not related to stress markers as healthy older adults' is. Future studies that include moderating variables are needed to explain the lack of association.

Clinical assessment of coiled fiducial markers as internal surrogates for hepatocellular carcinomas during gated stereotactic body radiotherapy with a real-time tumor-tracking system.

PubMed

Hanazawa, Hideki; Takahashi, Shotaro; Shiinoki, Takehiro; Park, Sung Chul; Yuasa, Yuki; Koike, Masahiro; Kawamura, Shinji; Shibuya, Keiko

2017-04-01

To report the clinical usefulness of coiled fiducial markers as an internal surrogate in gated stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) using a real-time tumor-tracking radiotherapy (RTRT) system. Seventeen HCC patients with Child-Pugh (CP) scores of A or B received gated SBRT (45-50Gy in 5-10 fractions) using an RTRT system and Visicoil markers. Local control (LC), progression-free (PFS), and overall survival (OS) rates were assessed using the Kaplan-Meier method. Toxicities were assessed using the Common Terminology Criteria for Adverse Events, Version 4.0. Of the 17 patients, 14 had a CP score A. The mean planning target volume was 54.6cc. Only 1 patient developed pneumothorax after marker implantation. Visicoil tracking during SBRT was possible in all cases. With a median follow-up of 16months, 1-year LC, PFS, and OS rates were 100%, 53%, and 82%, respectively. Grade≥2 late toxicity was observed in 2 patients (grade 2 duodenal ulcer and grade 3 temporary transaminase elevation). Using an RTRT system and Visicoil markers, gated SBRT was well tolerated in patients with HCC. This can be considered a safe treatment strategy with potential for delivering favorable outcomes. Copyright © 2017 Elsevier B.V. All rights reserved.

Independent Prognostic Value of Serum Markers in Diffuse Large B-Cell Lymphoma in the Era of the NCCN-IPI.

PubMed

Melchardt, Thomas; Troppan, Katharina; Weiss, Lukas; Hufnagl, Clemens; Neureiter, Daniel; Tränkenschuh, Wolfgang; Schlick, Konstantin; Huemer, Florian; Deutsch, Alexander; Neumeister, Peter; Greil, Richard; Pichler, Martin; Egle, Alexander

2015-12-01

Several serum parameters have been evaluated for adding prognostic value to clinical scoring systems in diffuse large B-cell lymphoma (DLBCL), but none of the reports used multivariate testing of more than one parameter at a time. The goal of this study was to validate widely available serum parameters for their independent prognostic impact in the era of the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score to determine which were the most useful. This retrospective bicenter analysis includes 515 unselected patients with DLBCL who were treated with rituximab and anthracycline-based chemoimmunotherapy between 2004 and January 2014. Anemia, high C-reactive protein, and high bilirubin levels had an independent prognostic value for survival in multivariate analyses in addition to the NCCN-IPI, whereas neutrophil-to-lymphocyte ratio, high gamma-glutamyl transferase levels, and platelets-to-lymphocyte ratio did not. In our cohort, we describe the most promising markers to improve the NCCN-IPI. Anemia and high C-reactive protein levels retain their power in multivariate testing even in the era of the NCCN-IPI. The negative role of high bilirubin levels may be associated as a marker of liver function. Further studies are warranted to incorporate these markers into prognostic models and define their role opposite novel molecular markers. Copyright © 2015 by the National Comprehensive Cancer Network.

Biomarkers to monitor safety in people on art and risk of mortality.

PubMed

Bansi, Loveleen; Gazzard, Brian; Post, Frank; Phillips, Andrew; Johnson, Margaret; Hill, Teresa; Gilson, Richard; Leen, Clifford; Walsh, John; Fisher, Martin; Sabin, Caroline

2012-05-01

Though patients with HIV now have near normal life expectancies as a result of antiretroviral treatment, long-term adverse effects are of growing concern. Using time-updated laboratory measurements, we use several methods to derive a score that can be used to identify individuals at high risk of mortality. Patients who started highly active antiretroviral therapy after 2000 and had ≥1 CD4 count, viral load, and laboratory marker recorded after the date of starting highly active antiretroviral therapy were included in the analyses. Laboratory markers were stratified into quintiles and associations between each marker and mortality was assessed using Poisson regression. The estimates of the final model were used to construct a score for predicting short-term mortality. Several methods, including multiple imputation, were used for analyzing records with missing measurements. Of the 7232 patients included in this analysis, 247 died over 24,796 person-years of follow-up, giving an overall mortality rate of 1.00 (95% confidence interval: 0.87 to 1.12) per 100 person-years. Regardless of which method was used to deal with missing data, albumin, alkaline phosphatase, and hemoglobin were independently associated with mortality. Alanine transaminase was independently associated with mortality when patients with missing measurements were assumed to have measurements within the normal range. The C-statistics for all models ranged from 0.76 to 0.78. Measures of alanine transaminase, albumin, alkaline phosphatase, and hemoglobin in the normal range were predictive of mortality, and hence we suggest using a scoring system to predict mortality which relies on the raw values of these 4 laboratory markers.

Serum cytokine tumor necrosis factor-alpha and interleukin-6 associated with the severity of coronary artery disease: indicators of an active inflammatory burden?

PubMed

Gotsman, Israel; Stabholz, Ayala; Planer, David; Pugatsch, Thea; Lapidus, Ludmila; Novikov, Yelena; Masrawa, Siham; Soskolne, Aubrey; Lotan, Chaim

2008-07-01

Atherosclerosis is a chronic inflammatory process resulting in coronary artery disease. To determine the relationship between inflammatory markers and the angiographic severity of CAD. We measured inflammatory markers in consecutive patients undergoing coronary angiography. This included C-reactive protein, fibrinogen, serum cytokines (interleukin-1 beta, IL-1 receptor antagonist, IL-6, IL-8, IL-10) and tumor necrosis factor-alpha), all measured by high sensitivity enzyme-linked immunoabsorbent assay. There was a significant correlation between TNFalpha and the severity of CAD as assessed by the number of obstructed coronary vessels and the Gensini severity score, which is based on the proximity and severity of the lesions. Patients had more coronary vessel disease (> 70% stenosis) with increasing tertiles of serum TNFalpha; the mean number of vessels affected was 1.15, 1.33, and 2.00 respectively (P< 0.001). IL-6 correlated with the Gensini severity score and coronary vessel disease (> 70% stenosis). A weaker correlation was present with IL-1 receptor antagonist. A significant correlation was not found with the other inflammatory markers. After adjustment for major risk factors, multivariate analyses showed that significant independent predictors of CAD vessel disease were TNFalpha (P< 0.05) and combined levels of TNFalpha and IL-6 (P< 0.05). IL-6 levels were independently predictive of Gensini coronary score (P< 0.05). TNFalpha and IL-6 are significant predictors of the severity of coronary artery disease. This association is likely an indicator of the chronic inflammatory burden and an important marker of increased atherosclerosis risk.

Increased Oxidative Stress Markers in Cerebrospinal Fluid from Healthy Subjects with Parkinson's Disease-Associated LRRK2 Gene Mutations.

PubMed

Loeffler, David A; Klaver, Andrea C; Coffey, Mary P; Aasly, Jan O; LeWitt, Peter A

2017-01-01

Mutations in the leucine-rich repeat kinase 2 ( LRRK2 ) gene are the most frequent cause of inherited Parkinson's disease (PD). The most common PD-associated LRRK2 mutation, G2019S, induces increased production of reactive oxygen species in vitro . We therefore hypothesized that individuals with PD-associated LRRK2 mutations might have increased concentrations of oxidative stress markers and/or decreased total antioxidant capacity (TAC) in their cerebrospinal fluid (CSF). We measured two oxidative stress markers, namely 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-isoprostane (8-ISO), and TAC in CSF from LRRK2 mutation-bearing PD patients ( LRRK2 PD = 19), sporadic PD patients (sPD = 31), and healthy control subjects with or without these mutations ( LRRK2 CTL = 30, CTL = 27). 8-OHdG and 8-ISO levels were increased in LRRK2 CTL subjects, while TAC was similar between groups. 8-ISO was negatively correlated, and TAC was positively correlated, with Montreal Cognitive Assessment scores in LRRK2 PD, LRRK2 CTL, and CTL subjects. Correlations in both groups of PD patients between the two oxidative stress markers and Unified Parkinson Disease Rating Scale Total scores were weak, while TAC was negatively correlated with these scores. These findings suggest that oxidative stress may be increased in the CNS in healthy individuals with PD-associated LRRK2 mutations. Further, TAC may decrease in the CNS with the progression of PD, and when cognitive impairment is present regardless of the presence or absence of PD.

Increased Oxidative Stress Markers in Cerebrospinal Fluid from Healthy Subjects with Parkinson’s Disease-Associated LRRK2 Gene Mutations

PubMed Central

Loeffler, David A.; Klaver, Andrea C.; Coffey, Mary P.; Aasly, Jan O.; LeWitt, Peter A.

2017-01-01

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most frequent cause of inherited Parkinson’s disease (PD). The most common PD-associated LRRK2 mutation, G2019S, induces increased production of reactive oxygen species in vitro. We therefore hypothesized that individuals with PD-associated LRRK2 mutations might have increased concentrations of oxidative stress markers and/or decreased total antioxidant capacity (TAC) in their cerebrospinal fluid (CSF). We measured two oxidative stress markers, namely 8-hydroxy-2′-deoxyguanosine (8-OHdG) and 8-isoprostane (8-ISO), and TAC in CSF from LRRK2 mutation-bearing PD patients (LRRK2 PD = 19), sporadic PD patients (sPD = 31), and healthy control subjects with or without these mutations (LRRK2 CTL = 30, CTL = 27). 8-OHdG and 8-ISO levels were increased in LRRK2 CTL subjects, while TAC was similar between groups. 8-ISO was negatively correlated, and TAC was positively correlated, with Montreal Cognitive Assessment scores in LRRK2 PD, LRRK2 CTL, and CTL subjects. Correlations in both groups of PD patients between the two oxidative stress markers and Unified Parkinson Disease Rating Scale Total scores were weak, while TAC was negatively correlated with these scores. These findings suggest that oxidative stress may be increased in the CNS in healthy individuals with PD-associated LRRK2 mutations. Further, TAC may decrease in the CNS with the progression of PD, and when cognitive impairment is present regardless of the presence or absence of PD. PMID:28420983

Development of DArT markers and assessment of diversity in Fusarium oxysporum f. sp. ciceris, wilt pathogen of chickpea (Cicer arietinum L.).

PubMed

Sharma, Mamta; Nagavardhini, Avuthu; Thudi, Mahendar; Ghosh, Raju; Pande, Suresh; Varshney, Rajeev K

2014-06-10

Fusarium oxysporum f. sp. ciceris (Foc), the causal agent of Fusarium wilt of chickpea is highly variable and frequent recurrence of virulent forms have affected chickpea production and exhausted valuable genetic resources. The severity and yield losses of Fusarium wilt differ from place to place owing to existence of physiological races among isolates. Diversity study of fungal population associated with a disease plays a major role in understanding and devising better disease control strategies. The advantages of using molecular markers to understand the distribution of genetic diversity in Foc populations is well understood. The recent development of Diversity Arrays Technology (DArT) offers new possibilities to study the diversity in pathogen population. In this study, we developed DArT markers for Foc population, analysed the genetic diversity existing within and among Foc isolates, compared the genotypic and phenotypic diversity and infer the race scenario of Foc in India. We report the successful development of DArT markers for Foc and their utility in genotyping of Foc collections representing five chickpea growing agro-ecological zones of India. The DArT arrays revealed a total 1,813 polymorphic markers with an average genotyping call rate of 91.16% and a scoring reproducibility of 100%. Cluster analysis, principal coordinate analysis and population structure indicated that the different isolates of Foc were partially classified based on geographical source. Diversity in Foc population was compared with the phenotypic variability and it was found that DArT markers were able to group the isolates consistent with its virulence group. A number of race-specific unique and rare alleles were also detected. The present study generated significant information in terms of pathogenic and genetic diversity of Foc which could be used further for development and deployment of region-specific resistant cultivars of chickpea. The DArT markers were proved to be a powerful diagnostic tool to study the genotypic diversity in Foc. The high number of DArT markers allowed a greater resolution of genetic differences among isolates and enabled us to examine the extent of diversity in the Foc population present in India, as well as provided support to know the changing race scenario in Foc population.

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

Intakes and sources of dietary sugars and their association with metabolic and inflammatory markers.

PubMed

O'Connor, Laura; Imamura, Fumiaki; Brage, Soren; Griffin, Simon J; Wareham, Nicholas J; Forouhi, Nita G

2018-08-01

Associations of dietary sugars with metabolic and inflammatory markers may vary according to the source of the sugars. The aim of this study was to examine the association of dietary sugars from different sources [beverages (liquids), foods (solids), extrinsic (free) or intrinsic (non-free)] with metabolic and inflammatory markers. Population-based cross-sectional study of adults in the East of England (n = 9678). Sugar intakes were estimated using food frequency questionnaires. Fasting glycated haemoglobin, glucose, insulin, and C-Reactive Protein (CRP) were measured and indices of metabolic risk were derived (homeostatic model of insulin resistance, HOMA-IR and metabolic risk z-score). In multiple linear regression analyses adjusted for potential confounders including BMI and TEI, sugars from liquids were positively associated with ln-CRP [b-coefficient (95%CI), 0.14 (0.05,0.22) per 10%TEI] and metabolic risk z-score [0.13 (0.07,0.18)]. Free sugars were positively associated with ln-HOMA-IR [0.05 (0.03,0.08)] and metabolic risk z-score [0.09 (0.06,0.12)]. Sugars from solids were not associated with any outcome. Among major dietary contributors to intakes (g/d), sugars in fruit, vegetables, dairy products/egg dishes, cakes/biscuits/confectionary and squash/juice drinks were not associated, but sugar added to tea, coffee, cereal was significantly positively associated with all outcomes. Sugars in 100% juice [0.16 (0.06,0.25) per 10%TEI] and other non-alcoholic beverages [0.13 (0.03,0.23)] were positively associated with metabolic risk z-score. Higher intakes of sugars from non-alcoholic beverages and sugar added to tea, coffee, cereal were associated with glycaemia and inflammatory markers. Sugars from solids were not associated, irrespective of whether they were intrinsic or extrinsic. Positive associations of free sugars were largely explained by contribution of beverages to intake. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Soluble RAGE as a severity marker in community acquired pneumonia associated sepsis

PubMed Central

2012-01-01

Background Community-acquired pneumonia (CAP) is considered the most important cause of death from infectious disease in developed countries. Severity assessment scores partially address the difficulties in identifying high-risk patients. A lack of specific and valid pathophysiologic severity markers affect early and effective sepsis therapy. HMGB-1, sRAGE and RAGE have been involved in sepsis and their potential as severity markers has been proposed. The aim of this study was to evaluate HMGB-1, RAGE and sRAGE levels in patients with CAP-associated sepsis and determine their possible association with clinical outcome. Method We evaluated 33 patients with CAP-associated sepsis admitted to the emergency room and followed in the medical wards. Severity assessment scores (CURB-65, PSI, APACHE II, SOFA) and serologic markers (HMGB-1, RAGE, sRAGE) were evaluated on admission. Results Thirty patients with a diagnosis of CAP-associated sepsis were enrolled in the study within 24 hours after admission. Fourteen (46.6%) had pandemic (H1N1) influenza A virus, 2 (6.6%) had seasonal influenza A and 14 other diagnoses. Of the patients in the study group, 16 (53.3%) had a fatal outcome. ARDS was observed in 17 (56.6%) and a total of 22 patients had severe sepsis on admission (73%). The SOFA score showed the greatest difference between surviving and non-surviving groups (P = .003) with similar results in ARDS patients (P = .005). sRAGE levels tended to be higher in non-surviving (P = .058) and ARDS patients (P = .058). Logistic regression modeling demonstrated that SOFA (P = .013) and sRAGE (P = .05) were the only variables that modified the probability of a fatal outcome. Conclusion The association of elevated sRAGE with a fatal outcome suggests that it may have an independent causal effect in CAP. SOFA scores were the only clinical factor with the ability to identify surviving and ARDS patients. PMID:22264245

Refining success of cardiac resynchronization therapy using a simple score predicting the amount of reverse ventricular remodelling: results from the Markers and Response to CRT (MARC) study.

PubMed

Maass, Alexander H; Vernooy, Kevin; Wijers, Sofieke C; van 't Sant, Jetske; Cramer, Maarten J; Meine, Mathias; Allaart, Cornelis P; De Lange, Frederik J; Prinzen, Frits W; Gerritse, Bart; Erdtsieck, Erna; Scheerder, Coert O S; Hill, Michael R S; Scholten, Marcoen; Kloosterman, Mariëlle; Ter Horst, Iris A H; Voors, Adriaan A; Vos, Marc A; Rienstra, Michiel; Van Gelder, Isabelle C

2018-02-01

Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in systolic heart failure patients with ventricular conduction delay. Variability of individual response to CRT warrants improved patient selection. The Markers and Response to CRT (MARC) study was designed to investigate markers related to response to CRT. We prospectively studied the ability of 11 clinical, 11 electrocardiographic, 4 echocardiographic, and 16 blood biomarkers to predict CRT response in 240 patients. Response was measured by the reduction of indexed left ventricular end-systolic volume (LVESVi) at 6 months follow-up. Biomarkers were related to LVESVi change using log-linear regression on continuous scale. Covariates that were significant univariately were included in a multivariable model. The final model was utilized to compose a response score. Age was 67 ± 10 years, 63% were male, 46% had ischaemic aetiology, LV ejection fraction was 26 ± 8%, LVESVi was 75 ± 31 mL/m2, and QRS was 178 ± 23 ms. At 6 months LVESVi was reduced to 58 ± 31 mL/m2 (relative reduction of 22 ± 24%), 130 patients (61%) showed ≥ 15% LVESVi reduction. In univariate analysis 17 parameters were significantly associated with LVESVi change. In the final model age, QRSAREA (using vectorcardiography) and two echocardiographic markers (interventricular mechanical delay and apical rocking) remained significantly associated with the amount of reverse ventricular remodelling. This CAVIAR (CRT-Age-Vectorcardiographic QRSAREA -Interventricular Mechanical delay-Apical Rocking) response score also predicted clinical outcome assessed by heart failure hospitalizations and all-cause mortality. The CAVIAR response score predicts the amount of reverse remodelling after CRT and may be used to improve patient selection. Clinical Trials: NCT01519908. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Microvascular function predicts cardiovascular events in primary prevention: long-term results from the Firefighters and Their Endothelium (FATE) study.

PubMed

Anderson, Todd J; Charbonneau, Francois; Title, Lawrence M; Buithieu, Jean; Rose, M Sarah; Conradson, Heather; Hildebrand, Kathy; Fung, Marinda; Verma, Subodh; Lonn, Eva M

2011-01-18

Biomarkers of atherosclerosis may refine clinical decision making in individuals at risk of cardiovascular disease. The purpose of the study was to determine the prognostic significance of endothelial function and other vascular markers in apparently healthy men. The cohort consisted of 1574 men (age, 49.4 years) free of vascular disease. Measurements included flow-mediated dilation and its microvascular stimulus, hyperemic velocity, carotid intima-media thickness, and C-reactive protein. Cox proportional hazard models evaluated the relationship between vascular markers, Framingham risk score, and time to a first composite cardiovascular end point of vascular death, revascularization, myocardial infarction, angina, and stroke. Subjects had low median Framingham risk score (7.9%). Cardiovascular events occurred in 71 subjects (111 events) over a mean follow-up of 7.2±1.7 years. Flow-mediated dilation was not associated with subsequent cardiovascular events (hazard ratio, 0.92; P=0.54). Both hyperemic velocity (hazard ratio, 0.70; 95% confidence interval, 0.54 to 0.90; P=0.006) and carotid intima-media thickness (hazard ratio, 1.45; confidence interval, 1.15 to 1.83; P=0.002) but not C-reactive protein (P=0.35) were related to events in a multivariable analysis that included Framingham risk score (per unit SD). Furthermore, the addition of hyperemic velocity to Framingham risk score resulted in a net clinical reclassification improvement of 28.7% (P<0.001) after 5 years of follow-up in the intermediate-risk group. Overall net reclassification improvement for hyperemic velocity was 6.9% (P=0.24). In men, hyperemic velocity, the stimulus for flow-mediated dilation, but not flow-mediated dilation itself was a significant risk marker for adverse cardiovascular outcomes. The prognostic value was additive to traditional risk factors and carotid intima-media thickness. Hyperemic velocity, a newly described marker of microvascular function, is a novel tool that may improve risk stratification of lower-risk healthy men.

High Resolution Mapping of Genetic Factors Affecting Abdominal Bristle Number in Drosophila Melanogaster

PubMed Central

Long, A. D.; Mullaney, S. L.; Reid, L. A.; Fry, J. D.; Langley, C. H.; Mackay, TFC.

1995-01-01

Factors responsible for selection response for abdominal bristle number and correlated responses in sternopleural bristle number were mapped to the X and third chromosome of Drosophila melanogaster. Lines divergent for high and low abdominal bristle number were created by 25 generations of artificial selection from a large base population, with an intensity of 25 individuals of each sex selected from 100 individuals of each sex scored per generation. Isogenic chromosome substitution lines in which the high (H) X or third chromosome were placed in an isogenic low (L) background were derived from the selection lines and from the 93 recombinant isogenic (RI) HL X and 67 RI chromosome 3 lines constructed from them. Highly polymorphic neutral r00 transposable elements were hybridized in situ to the polytene chromosomes of the RI lines to create a set of cytogenetic markers. These techniques yielded a dense map with an average spacing of 4 cM between informative markers. Factors affecting bristle number, and relative viability of the chromosome 3 RI lines, were mapped using a multiple regression interval mapping approach, conditioning on all markers >/=10 cM from the tested interval. Two factors with large effects on abdominal bristle number were mapped on the X chromosome and five factors on the third chromosome. One factor with a large effect on sternopleural bristle number was mapped to the X and two were mapped to the third chromosome; all factors with sternopleural effects corresponded to those with effects on abdominal bristle number. Two of the chromosome 3 factors with large effects on abdominal bristle number were also associated with reduced viability. Significant sex-specific effects and epistatic interactions between mapped factors of the same order of magnitude as the additive effects were observed. All factors mapped to the approximate positions of likely candidate loci (ASC, bb, emc, h, mab, Dl and E(spl)), previously characterized by mutations with large effects on bristle number. PMID:7768438

NOTE: A feasibility study of markerless fluoroscopic gating for lung cancer radiotherapy using 4DCT templates

NASA Astrophysics Data System (ADS)

Li, Ruijiang; Lewis, John H.; Cerviño, Laura I.; Jiang, Steve B.

2009-10-01

A major difficulty in conformal lung cancer radiotherapy is respiratory organ motion, which may cause clinically significant targeting errors. Respiratory-gated radiotherapy allows for more precise delivery of prescribed radiation dose to the tumor, while minimizing normal tissue complications. Gating based on external surrogates is limited by its lack of accuracy, while gating based on implanted fiducial markers is limited primarily by the risk of pneumothorax due to marker implantation. Techniques for fluoroscopic gating without implanted fiducial markers (markerless gating) have been developed. These techniques usually require a training fluoroscopic image dataset with marked tumor positions in the images, which limits their clinical implementation. To remove this requirement, this study presents a markerless fluoroscopic gating algorithm based on 4DCT templates. To generate gating signals, we explored the application of three similarity measures or scores between fluoroscopic images and the reference 4DCT template: un-normalized cross-correlation (CC), normalized cross-correlation (NCC) and normalized mutual information (NMI), as well as average intensity (AI) of the region of interest (ROI) in the fluoroscopic images. Performance was evaluated using fluoroscopic and 4DCT data from three lung cancer patients. On average, gating based on CC achieves the highest treatment accuracy given the same efficiency, with a high target coverage (average between 91.9% and 98.6%) for a wide range of nominal duty cycles (20-50%). AI works well for two patients out of three, but failed for the third patient due to interference from the heart. Gating based on NCC and NMI usually failed below 50% nominal duty cycle. Based on this preliminary study with three patients, we found that the proposed CC-based gating algorithm can generate accurate and robust gating signals when using 4DCT reference template. However, this observation is based on results obtained from a very limited dataset, and further investigation on a larger patient population has to be done before its clinical implementation.

Cell Free DNA and Procalcitonin as Early Markers of Complications in ICU Patients with Multiple Trauma and Major Surgery.

PubMed

Ahmed, Asmaa I; Soliman, Randa A; Samir, Shereif

2016-12-01

Cell free DNA (cfDNA) was recently suggested as a new marker of sepsis and poor outcome in ICU patients. Procalcitonin has also been the focus of attention as an early marker for systemic inflammation and sepsis. cfDNA, procalcitonin (PCT), C-reactive protein (CRP), and lactate levels were measured in 30 ICU patients with multiple trauma or after major surgery on the first day of admission and on 5th and 7th days for PCT, CRP, and lactate. cfDNA was measured by real-time PCR, PCT by ELISA, CRP immunoturbidimetrically, and lactate spectrophotometrically. SOFA score and Injury Severity Score (ISS) for trauma patients were calculated. Significantly higher levels of cfDNA were observed in non-survivor patients in comparison to survivors and in patients with sepsis in comparison to those without sepsis (p = 0.002 and p = 0.02, respectively). The ROC curve was calculated for cfDNA as a predictor of outcome, the area under the curve (AUC) was 0.847 (95% CI: 0.669 - 0.952), at a cutoff value of 15500 ng/µL, sensitivity = 83.3%, specificity = 77.8% (p < 0.0001). As a prognostic marker of sepsis, the AUC for cfDNA was 0.788 (95% CI: 0.601 - 0.915), sensitivity = 56.25%, specificity = 100% (p = 0.0007). Day 5 PCT levels significantly correlated with SOFA scores on day 5, ISS on admission (p < 0.001 and p = 0.028, respectively), and a significant elevation of its levels was observed in non-survivor patients compared to survivors (p = 0.001). As a predictor of sepsis, PCT showed a sensitivity of 81.3%, specificity of 100% on day 5, (AUC: 0.987, 95% CI: 0.955 - 1.00); at a cutoff value of 202.90 pg/mL (p = 0.001). As a predictor of outcome, PCT on day 5 showed a sensitivity of 94.0% and a specificity of 78.0% at a cutoff value of 194.40 pg/mL (p = 0.001). Day 1 CRP correlated with ISS on admission, and on day 5 it correlated with SOFA score 5, while lactate correlated with length of stay on days 1, 5, and 7, and its levels were significantly higher in non-survivors on days 5 and 7. cfDNA is a good predictor of patient outcome in ICU and to a lesser extent as a marker of sepsis. PCT is another promising marker that can complement cfDNA to reach better patient management. Other markers can help in less severe cases.

Polymorphic Microsatellite Markers for the Tetrapolar Anther-Smut Fungus Microbotryum saponariae Based on Genome Sequencing

PubMed Central

Fortuna, Taiadjana M.; Snirc, Alodie; Badouin, Hélène; Gouzy, Jérome; Siguenza, Sophie; Esquerre, Diane; Le Prieur, Stéphanie; Shykoff, Jacqui A.; Giraud, Tatiana

2016-01-01

Background Anther-smut fungi belonging to the genus Microbotryum sterilize their host plants by aborting ovaries and replacing pollen by fungal spores. Sibling Microbotryum species are highly specialized on their host plants and they have been widely used as models for studies of ecology and evolution of plant pathogenic fungi. However, most studies have focused, so far, on M. lychnidis-dioicae that parasitizes the white campion Silene latifolia. Microbotryum saponariae, parasitizing mainly Saponaria officinalis, is an interesting anther-smut fungus, since it belongs to a tetrapolar lineage (i.e., with two independently segregating mating-type loci), while most of the anther-smut Microbotryum fungi are bipolar (i.e., with a single mating-type locus). Saponaria officinalis is a widespread long-lived perennial plant species with multiple flowering stems, which makes its anther-smut pathogen a good model for studying phylogeography and within-host multiple infections. Principal Findings Here, based on a generated genome sequence of M. saponariae we developed 6 multiplexes with a total of 22 polymorphic microsatellite markers using an inexpensive and efficient method. We scored these markers in fungal individuals collected from 97 populations across Europe, and found that the number of their alleles ranged from 2 to 11, and their expected heterozygosity from 0.01 to 0.58. Cross-species amplification was examined using nine other Microbotryum species parasitizing hosts belonging to Silene, Dianthus and Knautia genera. All loci were successfully amplified in at least two other Microbotryum species. Significance These newly developed markers will provide insights into the population genetic structure and the occurrence of within-host multiple infections of M. saponariae. In addition, the draft genome of M. saponariae, as well as one of the described markers will be useful resources for studying the evolution of the breeding systems in the genus Microbotryum and the evolution of specialization onto different plant species. PMID:27832131

Population genetics-informed meta-analysis in seven genes associated with risk to dengue fever disease.

PubMed

Oliveira, Marisa; Saraiva, Diana P; Cavadas, Bruno; Fernandes, Verónica; Pedro, Nicole; Casademont, Isabelle; Koeth, Fanny; Alshamali, Farida; Harich, Nourdin; Cherni, Lotfi; Sierra, Beatriz; Guzman, Maria G; Sakuntabhai, Anavaj; Pereira, Luisa

2018-04-17

Population genetics theory predicted that rare frequent markers would be the main contributors for heritability of complex diseases, but meta-analyses of genome-wide association studies are revealing otherwise common markers, present in all population groups, as the identified candidate genes. In this work, we applied a population-genetics informed meta-analysis to 10 markers located in seven genes said to be associated with dengue fever disease. Seven markers (in PLCE1, CD32, CD209, OAS1 and OAS3 genes) have high-frequency and the other three (in MICB and TNFA genes) have intermediate frequency. Most of these markers have high discriminatory power between population groups, but their frequencies follow the rules of genetic drift, and seem to have not been under strong selective pressure. There was a good agreement in directional consistency across trans-ethnic association signals, in East Asian and Latin American cohorts, with heterogeneity generated by randomness between studies and especially by low sample sizes. This led to confirm the following significant associations: with DF, odds ratio of 0.67 for TNFA-rs1800629-A; with DHF, 0.82 for CD32-rs1801274-G; with DSS, 0.55 for OAS3-rs2285933-G, 0.80 for PLCE1-rs2274223-G and 1.32 for MICB-rs3132468-C. The overall genetic risks confirmed sub-Saharan African populations and descendants as the best protected against the severer forms of the disease, while Southeast and Northeast Asians are the least protected ones. European and close neighbours are the best protected against dengue fever, while, again, Southeast and Northeast Asians are the least protected ones. These risk scores provide important predictive information for the largely naïve European and North American regions, as well as for Africa where misdiagnosis with other hemorrhagic diseases is of concern. Copyright © 2018 Elsevier B.V. All rights reserved.

Differentiation among prostate cancer patients with Gleason score of 7 using histopathology whole-slide image and genomic data

NASA Astrophysics Data System (ADS)

Ren, Jian; Karagoz, Kubra; Gatza, Michael; Foran, David J.; Qi, Xin

2018-03-01

Prostate cancer is the most common non-skin related cancer affecting 1 in 7 men in the United States. Treatment of patients with prostate cancer still remains a difficult decision-making process that requires physicians to balance clinical benefits, life expectancy, comorbidities, and treatment-related side effects. Gleason score (a sum of the primary and secondary Gleason patterns) solely based on morphological prostate glandular architecture has shown as one of the best predictors of prostate cancer outcome. Significant progress has been made on molecular subtyping prostate cancer delineated through the increasing use of gene sequencing. Prostate cancer patients with Gleason score of 7 show heterogeneity in recurrence and survival outcomes. Therefore, we propose to assess the correlation between histopathology images and genomic data with disease recurrence in prostate tumors with a Gleason 7 score to identify prognostic markers. In the study, we identify image biomarkers within tissue WSIs by modeling the spatial relationship from automatically created patches as a sequence within WSI by adopting a recurrence network model, namely long short-term memory (LSTM). Our preliminary results demonstrate that integrating image biomarkers from CNN with LSTM and genomic pathway scores, is more strongly correlated with patients recurrence of disease compared to standard clinical markers and engineered image texture features. The study further demonstrates that prostate cancer patients with Gleason score of 4+3 have a higher risk of disease progression and recurrence compared to prostate cancer patients with Gleason score of 3+4.

Proteomic Candidate Biomarkers of Drug-Induced Nephrotoxicity in the Rat

PubMed Central

Rouse, Rodney; Siwy, Justyna; Mullen, William; Mischak, Harald; Metzger, Jochen; Hanig, Joseph

2012-01-01

Improved biomarkers of acute nephrotoxicity are coveted by the drug development industry, regulatory agencies, and clinicians. In an effort to identify such biomarkers, urinary peptide profiles of rats treated with two different nephrotoxins were investigated. 493 marker candidates were defined that showed a significant response to cis-platin comparing a cis-platin treated cohort to controls. Next, urine samples from rats that received three consecutive daily doses of 150 or 300 mg/kg gentamicin were examined. 557 potential biomarkers were initially identified; 108 of these gentamicin-response markers showed a clear temporal response to treatment. 39 of the cisplatin-response markers also displayed a clear response to gentamicin. Of the combined 147 peptides, 101 were similarly regulated by gentamicin or cis-platin and 54 could be identified by tandem mass spectrometry. Most were collagen type I and type III fragments up-regulated in response to gentamicin treatment. Based on these peptides, classification models were generated and validated in a longitudinal study. In agreement with histopathology, the observed changes in classification scores were transient, initiated after the first dose, and generally persistent over a period of 10–20 days before returning to control levels. The data support the hypothesis that gentamicin-induced renal toxicity up-regulates protease activity, resulting in an increase in several specific urinary collagen fragments. Urinary proteomic biomarkers identified here, especially those common to both nephrotoxins, may serve as a valuable tool to investigate potential new drug candidates for the risk of nephrotoxicity. PMID:22509332

Comprehensive malnutrition inflammation score as a marker of nutritional status in Chinese peritoneal dialysis patients.

PubMed

Chan, Jessie Ying Wing; Che, Kit I; Lam, Karry Mau Chu; Chow, Kai-Ming; Chung, Kwok-Yi; Li, Philip Kam-Tao; Szeto, Cheuk-Chun

2007-04-01

Malnutrition is common among peritoneal dialysis (PD) patients. However, the ideal marker of nutritional status in PD patients remained controversial. We studied 165 unselected adult PD patients. We compared the comprehensive Malnutrition-Inflammation Score (MIS) and the 7-point Subjective Global Assessment (SGA) score. The mean age was 59.2 +/- 11.5 years. Seventy patients were male. MIS significantly correlated with the SGA score (r =-0.667, P < 0.001). Of the 165 patients, 132 (80.0%) had similar classification of nutritional status by SGA and MIS (Group I); 17 (10.3%) were classified as normal by SGA but moderately malnourished by MIS (Group II), while 16 (9.7%) were classified as normal by MIS but moderately malnourished by SGA (Group III). Group II had been dialysed longer than Group I (71.7 +/- 50.3 vs 40.7 +/- 37.5 months, P = 0.011). As compared with Group I, Group III was more likely to require helper for PD exchange (37.5%vs 9.7%, P = 0.004), marginally more likely to be diabetic (62.5%vs 35.6%, P = 0.085) and had a slightly higher Charlson's comorbidity score (6.13 +/- 1.78 vs 4.98 +/- 2.1, P = 0.085), although the latter two were not statistically significant. MIS has a reasonable correlation with the conventional SGA score in PD patients. Patients with limited self-care capability, diabetes and multiple comorbidities probably had worse score (i.e. worse nutrition) revealed by SGA than by MIS, while patients who had been dialysed longer had worse score revealed by MIS than by SGA.

A Study of Correlation of Neck Circumference with Framingham Risk Score as a Predictor of Coronary Artery Disease.

PubMed

Koppad, Anand K; Kaulgud, Ram S; Arun, B S

2017-09-01

It has been observed that metabolic syndrome is risk factor for Coronary Artery Disease (CAD) and exerts its effects through fat deposition and vascular aging. CAD has been acknowledged as a leading cause of death. In earlier studies, the metabolic risk has been estimated by Framingham risk score. Recent studies have shown that Neck Circumference (NC) has a good correlation with other traditional anthropometric measurements and can be used as marker of obesity. It also correlates with Framingham risk score, which is slightly more sophisticated measure of CAD risk. To assess the risk of CAD in a subject based on NC and to correlate the NC to Framingham risk score. The present cross-sectional study, done at Karnataka Institute of Medical Sciences, Hubli, Karnataka, India, includes 100 subjects. The study duration was of one year from 1 st January 2015 to 31 st December 2015. Anthropometric indices Body Mass Index (BMI) and NC were correlated with 10 year CAD risk as calculated by Framingham risk score. The correlation between BMI, NC, vascular age and Framingham risk score was calculated using Karl Pearson's correlation method. NC has a strong correlation with 10 year CAD risk (p≤0.001). NC was significantly greater in males as compared to females (p≤0.001). Males had greater risk of cardiovascular disease as reflected by higher 10 year Framingham risk score (p≤0.0035). NC gives simple and easy prediction of CAD risk and is more reliable than traditional risk markers like BMI. NC correlates positively with 10 year Framingham risk score.

Linguistic Markers of Inference Generation While Reading

ERIC Educational Resources Information Center

Clinton, Virginia; Carlson, Sarah E.; Seipel, Ben

2016-01-01

Words can be informative linguistic markers of psychological constructs. The purpose of this study is to examine associations between word use and the process of making meaningful connections to a text while reading (i.e., inference generation). To achieve this purpose, think-aloud data from third-fifth grade students (N = 218) reading narrative…

Self-perceived personality characteristics in seasonal affective disorder and their implications for severity of depression.

PubMed

Hjordt, Liv Vadskjær; Dam, Vibeke H; Ozenne, Brice; Hageman, Ida; Mc Mahon, Brenda; Mortensen, Erik Lykke; Knudsen, Gitte M; Stenbæk, Dea Siggaard

2018-04-01

The personality traits Neuroticism and Extraversion may be involved in the development of seasonal affective disorder (SAD). However, the impact of personality traits on SAD severity and whether such self-reported traits fluctuate with season is unknown. We investigated the association between Neuroticism, as acquired in a symptom-free phase and depression severity in individuals with SAD and seasonal changes in personality traits in individuals with SAD compared to healthy controls. Twenty-nine individuals diagnosed with SAD and thirty demographically matched controls completed the NEO Personality Inventory-Revised and the Major Depression Inventory twice: in summer when individuals with SAD were symptom-free, and in winter when they experienced SAD symptoms. In summer, the groups scored similarly on their personality traits, and the controls did not score any different in winter compared to summer. High scores on Neuroticism in summer was associated with more severe depressive symptoms in winter in SAD individuals. In winter, individuals with SAD scored higher on Neuroticism and lower on Extraversion, both compared to controls and to their own summer scores. Our results support that Neuroticism may represent a vulnerability marker related to SAD, and during a depressive episode Neuroticism and Extraversion may be sensitive markers of SAD pathology. Copyright © 2018 Elsevier B.V. All rights reserved.

Biomarkers of Endothelial Activation Are Associated with Poor Outcome in Critical Illness.

PubMed

Mikacenic, Carmen; Hahn, William O; Price, Brenda L; Harju-Baker, Susanna; Katz, Ronit; Kain, Kevin C; Himmelfarb, Jonathan; Liles, W Conrad; Wurfel, Mark M

2015-01-01

Endothelial activation plays a role in organ dysfunction in the systemic inflammatory response syndrome (SIRS). Angiopoietin-1 (Ang-1) promotes vascular quiescence while angiopoietin-2 (Ang-2) mediates microvascular leak. Circulating levels of Ang-1 and Ang-2 in patients with SIRS could provide insight on risks for organ dysfunction and death distinct from inflammatory proteins. In this study, we determined if biomarkers of endothelial activation and inflammation exhibit independent associations with poor outcomes in SIRS. We studied 943 critically ill patients with SIRS admitted to an Intensive Care Unit (ICU) of an academic medical center. We measured plasma levels of endothelial markers (Ang-1, Ang-2, soluble vascular cell adhesion molecule-1 (sVCAM-1)) and inflammatory markers (interleukin-6 (IL-6), interleukin-8 (IL-8), granulocyte-colony stimulating factor (G-CSF), soluble tumor necrosis factor receptor-1 (sTNFR-1)) within 24 hours of enrollment. We tested for associations between each marker and 28 day mortality, shock, and day 3 sequential organ failure assessment (SOFA) score. For 28 day mortality, we performed sensitivity analysis for those subjects with sepsis and those with sterile inflammation. We used multivariate models to adjust for clinical covariates and determine if associations identified with endothelial activation markers were independent of those observed with inflammatory markers. Higher levels of all biomarkers were associated with increased 28 day mortality except levels of Ang-1 which were associated with lower mortality. After adjustment for comorbidities and sTNFR-1 concentration, a doubling of Ang-1 concentration was associated with lower 28 day mortality (Odds ratio (OR) = 0.81; p<0.01), shock (OR = 0.82; p<0.001), and SOFA score (β = -0.50; p<0.001), while Ang-2 concentration was associated with increased mortality (OR = 1.55; p<0.001), shock (OR = 1.51; p<0.001), and SOFA score (β = +0.63; p<0.001). sVCAM-1 was not independently associated with SIRS outcomes. In critically ill patients with SIRS, early measurements of Ang-1 and Ang-2 are associated with death and organ dysfunction independently of simultaneously-measured markers of inflammation.

Non-invasive fibrosis tests are correlated with necroinflammatory actvity of liver in patients with chronic hepatitis B.

PubMed

Ozyalvacli, G; Kucukbayrak, A; Kurt, M; Gurel, K; Gunes, O; Ustun, C; Akdeniz, H

2014-01-01

The gold standarda method used for assessing necroinflammatory activity and fibrosis in the liver is a liver biopsy which has many disadvantages. Therefore, many investigators have been trying to develop non-invasive tests for predicting liver fibrosis score (LFS) of these patients. The aim of this study is to describe the relationship between certain non-invasive fibrosis markers with LFS and histological activity index (HAI) detected histopathologically by liver biopsy in chronic hepatitis B patients. A total of 54 patients who had undergone a liver biopsy with the diagnosis of chronic HBV infection were included in the study. Ishak scoring was used for the evaluation of liver fibrosis, and a modified Knodell HAI was used for demonstration of necroinflammation. In this study, non-invasive fibrosis tests were calculated as described in previous studies. Histological acitivity index was positively correlated with age, age/platelet index, cirrhosis discriminant score (CDS), AST/platelet ratio index (APRI), AST/platelet/GGT/AFP index (APGA), fibro-quotient (Fibro-Q), Goteburg University Cirrhosis Index (Guci), and Platelet/Age/Phosphatase/AFP/AST index (PAPAS). When divided into two groups according to HAI, Guci and APGA were found significantly different both in >4 and >4 HAI groups than the other group. In ROC analysis performed for LFS; PAPAS, APGA, FFI and APRI were the markers having the highest AUC levels, and in ROC analysis performed for HAI; Guci, APRI and APGA were the markers with the highest AUC levels. APRI, APGA and GUCI tests may be helpful in prediction of necroinflammatory scores in the liver.

Ascertainment bias from imputation methods evaluation in wheat.

PubMed

Brandariz, Sofía P; González Reymúndez, Agustín; Lado, Bettina; Malosetti, Marcos; Garcia, Antonio Augusto Franco; Quincke, Martín; von Zitzewitz, Jarislav; Castro, Marina; Matus, Iván; Del Pozo, Alejandro; Castro, Ariel J; Gutiérrez, Lucía

2016-10-04

Whole-genome genotyping techniques like Genotyping-by-sequencing (GBS) are being used for genetic studies such as Genome-Wide Association (GWAS) and Genomewide Selection (GS), where different strategies for imputation have been developed. Nevertheless, imputation error may lead to poor performance (i.e. smaller power or higher false positive rate) when complete data is not required as it is for GWAS, and each marker is taken at a time. The aim of this study was to compare the performance of GWAS analysis for Quantitative Trait Loci (QTL) of major and minor effect using different imputation methods when no reference panel is available in a wheat GBS panel. In this study, we compared the power and false positive rate of dissecting quantitative traits for imputed and not-imputed marker score matrices in: (1) a complete molecular marker barley panel array, and (2) a GBS wheat panel with missing data. We found that there is an ascertainment bias in imputation method comparisons. Simulating over a complete matrix and creating missing data at random proved that imputation methods have a poorer performance. Furthermore, we found that when QTL were simulated with imputed data, the imputation methods performed better than the not-imputed ones. On the other hand, when QTL were simulated with not-imputed data, the not-imputed method and one of the imputation methods performed better for dissecting quantitative traits. Moreover, larger differences between imputation methods were detected for QTL of major effect than QTL of minor effect. We also compared the different marker score matrices for GWAS analysis in a real wheat phenotype dataset, and we found minimal differences indicating that imputation did not improve the GWAS performance when a reference panel was not available. Poorer performance was found in GWAS analysis when an imputed marker score matrix was used, no reference panel is available, in a wheat GBS panel.

Evidence of a locus for schizophrenia and related disorders on the short arm of chromosome 5 in a large pedigree

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

Silverman, J.M.; Altstiel, L.D.; Siever, L.J.

We attempted to identify a locus for schizophrenia and related disorders in 24 nuclear families of schizophrenic probands using a predefined classification system for affected cases that included those disorders most clearly identified as sharing a genetic relationship with schizophrenia-schizoaffective disorder and schizotypal personality disorder. Initially, we evaluated 8 markers on chromosome 5 on the first 12 families with available genotyping and diagnostic assessments and, assuming autosomal dominant transmission, found a lod score of 2.67 for the D5S111 locus (5p14.1-13.1) in one large nuclear family (no. 17; sibship: n = 12; schizophrenia: n = 3; schizotypal personality disorder: n =more » 2); the other 11 families were much smaller, less complete, and provided little additional information. Other branches of no. 17 were then assessed and the 2-point lod score for family 17 rose to 3.72; using multipoint analysis the lod score in 17 was 4.37. When only schizophrenia was used to define affectedness, the positive evidence for linkage to D5S111 was greatly reduced. Sensitivity analysis indicated that the lod score is heavily dependent upon the predefined diagnostic criteria. Our studies of other families of schizophrenic probands eventually totalled 23, but linkage to D5S111 in these yielded a -2.41 lod score. The results provide evidence for genetic linkage of the D5S111 locus to schizophrenia and related disorders in one family. It may be of interest that over several generations, almost all the ancestors of family 17 could be traced back to a small, relatively isolated, hill region of Puerto Rico. 74 refs., 2 figs., 2 tabs.« less

TS, DHFR and GARFT expression in non-squamous cell carcinoma of NSCLC and malignant pleural mesothelioma patients treated with pemetrexed.

PubMed

Uramoto, Hidetaka; Onitsuka, Takamitsu; Shimokawa, Hidehiko; Hanagiri, Takeshi

2010-10-01

Recently, pemetrexed (PEM), a new generation antifolate, has been used for the treatment of patients with advanced non-squamous cell carcinoma (SQ) of non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). However, no useful markers for selecting appropriate candidates exist at present. Tumor specimens were collected from 5 lung non-SQ and 8 MPM patients who underwent surgery and received PEM. Real-time PCR and immunohistochemical (IHC) staining of the primary tumor were used to analyze the mRNA and protein expressions of thymidylate synthase (TS)/dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), and to compare the expression status and clinical outcomes. TS, DHFR, and GARFT mRNA levels had a median value of 2.39, 1.70, and 1.40 in non-SQ samples of NSCLC patients. The TS and DHFR protein levels had a mean total score of 2 and 4 in non-SQ of NSCLC patients. TS, DHFR, and GARFT mRNA levels had a median value of 5.55, 3.73, and 3.52 in MPM patients. TS and DHFR protein levels had a mean total expression score of 1 and 3 in MPM patients. No significant correlation was identified between the expression levels of TS/DPD/GARFT mRNA and clinical response for the non-SQ of NSCLC and MPM patients treated with PEM. TS, DHFR, and GARFT mRNA and protein expression may not be useful markers for predicting clinical response in Japanese patients with non-SQ of NSCLC and MPM. Further investigations are necessary in order to develop biomarkers to determine the clinical benefits of PEM treatment.

Evaluation of SNP Data from the Malus Infinium Array Identifies Challenges for Genetic Analysis of Complex Genomes of Polyploid Origin.

PubMed

Troggio, Michela; Surbanovski, Nada; Bianco, Luca; Moretto, Marco; Giongo, Lara; Banchi, Elisa; Viola, Roberto; Fernández, Felicdad Fernández; Costa, Fabrizio; Velasco, Riccardo; Cestaro, Alessandro; Sargent, Daniel James

2013-01-01

High throughput arrays for the simultaneous genotyping of thousands of single-nucleotide polymorphisms (SNPs) have made the rapid genetic characterisation of plant genomes and the development of saturated linkage maps a realistic prospect for many plant species of agronomic importance. However, the correct calling of SNP genotypes in divergent polyploid genomes using array technology can be problematic due to paralogy, and to divergence in probe sequences causing changes in probe binding efficiencies. An Illumina Infinium II whole-genome genotyping array was recently developed for the cultivated apple and used to develop a molecular linkage map for an apple rootstock progeny (M432), but a large proportion of segregating SNPs were not mapped in the progeny, due to unexpected genotype clustering patterns. To investigate the causes of this unexpected clustering we performed BLAST analysis of all probe sequences against the 'Golden Delicious' genome sequence and discovered evidence for paralogous annealing sites and probe sequence divergence for a high proportion of probes contained on the array. Following visual re-evaluation of the genotyping data generated for 8,788 SNPs for the M432 progeny using the array, we manually re-scored genotypes at 818 loci and mapped a further 797 markers to the M432 linkage map. The newly mapped markers included the majority of those that could not be mapped previously, as well as loci that were previously scored as monomorphic, but which segregated due to divergence leading to heterozygosity in probe annealing sites. An evaluation of the 8,788 probes in a diverse collection of Malus germplasm showed that more than half the probes returned genotype clustering patterns that were difficult or impossible to interpret reliably, highlighting implications for the use of the array in genome-wide association studies.

Variable selection models for genomic selection using whole-genome sequence data and singular value decomposition.

PubMed

Meuwissen, Theo H E; Indahl, Ulf G; Ødegård, Jørgen

2017-12-27

Non-linear Bayesian genomic prediction models such as BayesA/B/C/R involve iteration and mostly Markov chain Monte Carlo (MCMC) algorithms, which are computationally expensive, especially when whole-genome sequence (WGS) data are analyzed. Singular value decomposition (SVD) of the genotype matrix can facilitate genomic prediction in large datasets, and can be used to estimate marker effects and their prediction error variances (PEV) in a computationally efficient manner. Here, we developed, implemented, and evaluated a direct, non-iterative method for the estimation of marker effects for the BayesC genomic prediction model. The BayesC model assumes a priori that markers have normally distributed effects with probability [Formula: see text] and no effect with probability (1 - [Formula: see text]). Marker effects and their PEV are estimated by using SVD and the posterior probability of the marker having a non-zero effect is calculated. These posterior probabilities are used to obtain marker-specific effect variances, which are subsequently used to approximate BayesC estimates of marker effects in a linear model. A computer simulation study was conducted to compare alternative genomic prediction methods, where a single reference generation was used to estimate marker effects, which were subsequently used for 10 generations of forward prediction, for which accuracies were evaluated. SVD-based posterior probabilities of markers having non-zero effects were generally lower than MCMC-based posterior probabilities, but for some regions the opposite occurred, resulting in clear signals for QTL-rich regions. The accuracies of breeding values estimated using SVD- and MCMC-based BayesC analyses were similar across the 10 generations of forward prediction. For an intermediate number of generations (2 to 5) of forward prediction, accuracies obtained with the BayesC model tended to be slightly higher than accuracies obtained using the best linear unbiased prediction of SNP effects (SNP-BLUP model). When reducing marker density from WGS data to 30 K, SNP-BLUP tended to yield the highest accuracies, at least in the short term. Based on SVD of the genotype matrix, we developed a direct method for the calculation of BayesC estimates of marker effects. Although SVD- and MCMC-based marker effects differed slightly, their prediction accuracies were similar. Assuming that the SVD of the marker genotype matrix is already performed for other reasons (e.g. for SNP-BLUP), computation times for the BayesC predictions were comparable to those of SNP-BLUP.

Construction of a genetic map using EST-SSR markers and QTL analysis of major agronomic characters in hexaploid sweet potato (Ipomoea batatas (L.) Lam).

PubMed

Kim, Jin-Hee; Chung, Il Kyung; Kim, Kyung-Min

2017-01-01

The Sweet potato, Ipomoea batatas (L.) Lam, is difficult to study in genetics and genomics because it is a hexaploid. The sweet potato study not have been performed domestically or internationally. In this study was performed to construct genetic map and quantitative trait loci (QTL) analysis. A total of 245 EST-SSR markers were developed, and the map was constructed by using 210 of those markers. The total map length was 1508.1 cM, and the mean distance between markers was 7.2 cM. Fifteen characteristics were investigated for QTLs analysis. According to those, the Four QTLs were identified, and The LOD score was 3.0. Further studies need to develop molecular markers in terms of EST-SSR markers for doing to be capable of efficient breeding. The genetic map created here using EST-SSR markers will facilitate planned breeding of sweet potato cultivars with various desirable traits.

Serum levels of keratin-18 fragments [tissue polypeptide-specific antigen (TPS)] are correlated with hepatocyte apoptosis in alcoholic hepatitis.

PubMed

Gonzalez-Quintela, A; Abdulkader, I; Campos, J; Fernandez-Hernandez, L; Lojo, S

2009-03-01

Apoptosis is a major feature in alcoholic hepatitis. During apoptosis, the M30 neoepitope becomes exposed after keratin-18 cleavage. The tissue polypeptide-specific antigen (TPS) is a keratin-18 fragment that is routinely used as a tumor marker. Serum TPS levels are increased in patients with alcoholic hepatitis. The aim of this study was to investigate the possible relationship of TPS levels with hepatocyte apoptosis in alcoholic hepatitis. Thirty-one patients with alcoholic hepatitis and 22 with fatty liver were included. Hepatocyte apoptosis was evaluated by M30 immunostaining. Serum TPS levels were measured by a commercial immunoassay. The apoptotic score was higher in patients with alcoholic hepatitis than in patients with fatty liver. There was a significant correlation between the apoptotic score and TPS levels. The correlation of the apoptotic score with TPS levels was stronger than with standard liver tests. Serum TPS may be a marker of apoptosis in alcoholic hepatitis.

Candidate Markers Associated with the Probability of Future Pulmonary Exacerbations in Cystic Fibrosis Patients

PubMed Central

Wojewodka, Gabriella; De Sanctis, Juan B.; Bernier, Joanie; Bérubé, Julie; Ahlgren, Heather G.; Gruber, Jim; Landry, Jennifer; Lands, Larry C.; Nguyen, Dao; Rousseau, Simon; Benedetti, Andrea; Matouk, Elias; Radzioch, Danuta

2014-01-01

Introduction Pulmonary exacerbations (PEs) cause significant morbidity and can severely impact disease progression in cystic fibrosis (CF) lung disease, especially in patients who suffer from recurrent PEs. The assessments able to predict a future PE or a recurrent PE are limited. We hypothesized that combining clinical, molecular and patient reported data could identify patients who are at risk of PE. Methods We prospectively followed a cohort of 53 adult CF patients for 24 months. Baseline values for spirometry, clinical status using the Matouk Disease Score, quality of life (QOL), inflammatory markers (C-reactive protein (CRP), interleukins (IL)-1β, -6, -8, -10, macrophage inflammatory protein (MIP)-1β, tumor necrosis factor (TNF) and vascular endothelial growth factor (VEGF)), polyunsaturated fatty acids and lipid peroxidation in blood plasma were collected for all patients during periods of stable disease, and patients were monitored for PE requiring PO/IV antibiotic treatment. Additionally, we closely followed 13 patients during PEs collecting longitudinal data on changes in markers from baseline values. We assessed whether any markers were predictors of future PE at baseline and after antibiotic treatment. Results Out of 53 patients, 37 experienced PEs during our study period. At baseline, we found that low lung function, clinical scoring and QOL values were associated with increased risk of PE events. PEs were associated with increased inflammatory markers at Day 1, and these biomarkers improved with treatment. The imbalance in arachidonic acid and docosahexaenoic acid levels improved with treatment which coincided with reductions in lipid peroxidation. High levels of inflammatory markers CRP and IL-8 were associated with an early re-exacerbation. Conclusion Our results demonstrate that worse clinical and QOL assessments during stable disease are potential markers associated with a higher risk of future PEs, while higher levels of inflammatory markers at the end of antibiotic treatment may be associated with early re-exacerbation. PMID:24533110

Multilocus lod scores in large pedigrees: combination of exact and approximate calculations.

PubMed

Tong, Liping; Thompson, Elizabeth

2008-01-01

To detect the positions of disease loci, lod scores are calculated at multiple chromosomal positions given trait and marker data on members of pedigrees. Exact lod score calculations are often impossible when the size of the pedigree and the number of markers are both large. In this case, a Markov Chain Monte Carlo (MCMC) approach provides an approximation. However, to provide accurate results, mixing performance is always a key issue in these MCMC methods. In this paper, we propose two methods to improve MCMC sampling and hence obtain more accurate lod score estimates in shorter computation time. The first improvement generalizes the block-Gibbs meiosis (M) sampler to multiple meiosis (MM) sampler in which multiple meioses are updated jointly, across all loci. The second one divides the computations on a large pedigree into several parts by conditioning on the haplotypes of some 'key' individuals. We perform exact calculations for the descendant parts where more data are often available, and combine this information with sampling of the hidden variables in the ancestral parts. Our approaches are expected to be most useful for data on a large pedigree with a lot of missing data. (c) 2007 S. Karger AG, Basel

Multilocus Lod Scores in Large Pedigrees: Combination of Exact and Approximate Calculations

PubMed Central

Tong, Liping; Thompson, Elizabeth

2007-01-01

To detect the positions of disease loci, lod scores are calculated at multiple chromosomal positions given trait and marker data on members of pedigrees. Exact lod score calculations are often impossible when the size of the pedigree and the number of markers are both large. In this case, a Markov Chain Monte Carlo (MCMC) approach provides an approximation. However, to provide accurate results, mixing performance is always a key issue in these MCMC methods. In this paper, we propose two methods to improve MCMC sampling and hence obtain more accurate lod score estimates in shorter computation time. The first improvement generalizes the block-Gibbs meiosis (M) sampler to multiple meiosis (MM) sampler in which multiple meioses are updated jointly, across all loci. The second one divides the computations on a large pedigree into several parts by conditioning on the haplotypes of some ‘key’ individuals. We perform exact calculations for the descendant parts where more data are often available, and combine this information with sampling of the hidden variables in the ancestral parts. Our approaches are expected to be most useful for data on a large pedigree with a lot of missing data. PMID:17934317

Does Council Tax Valuation Band (CTVB) correlate with Under-Privileged Area 8 (UPA8) score and could it be a better 'Jarman Index'?

PubMed Central

Beale, Norman; Taylor, Gordon; Straker-Cook, Dawn

2001-01-01

Background Widespread scepticism persists on the use of the Under-Privileged Area (UPA8) score of Jarman in distributing supplementary resources to so-attributed 'deprived' UK general practices. The search for better 'needs' markers continues. Having already shown that Council Tax Valuation Band (CTVB) is a predictor of UK GP workload, we compare, here, CTVB of residence of a random sample of patients with their respective 'Jarman' scores. Methods Correlation coefficient is calculated between (i) the CTVB of residence of a randomised sample of patients from an English general practice and (ii) the UPA8 scores of the relevant enumeration districts in which they live. Results There is a highly significant correlation between the two measures despite modest study size of 478 patients (85% response). Conclusions The proposal that CTVB is a marker of deprivation and of clinical demand should be examined in more detail: it correlates with 'Jarman', which is already used in NHS resource allocation. But unlike 'Jarman', CTVB is simple, objective, and free of the problems of Census data. CTVB, being household-based, can be aggregated at will. PMID:11716793

Does Council Tax Valuation Band (CTVB) correlate with Under-Privileged Area 8 (UPA8) score and could it be a better 'Jarman Index'?

PubMed

Beale, N; Taylor, G; Straker-Cook, D

2001-01-01

Widespread scepticism persists on the use of the Under-Privileged Area (UPA8) score of Jarman in distributing supplementary resources to so-attributed 'deprived' UK general practices. The search for better 'needs' markers continues. Having already shown that Council Tax Valuation Band (CTVB) is a predictor of UK GP workload, we compare, here, CTVB of residence of a random sample of patients with their respective 'Jarman' scores. Correlation coefficient is calculated between (i) the CTVB of residence of a randomised sample of patients from an English general practice and (ii) the UPA8 scores of the relevant enumeration districts in which they live. There is a highly significant correlation between the two measures despite modest study size of 478 patients (85% response). The proposal that CTVB is a marker of deprivation and of clinical demand should be examined in more detail: it correlates with 'Jarman', which is already used in NHS resource allocation. But unlike 'Jarman', CTVB is simple, objective, and free of the problems of Census data. CTVB, being household-based, can be aggregated at will.

Marker-Assisted Introgression in Backcross Breeding Programs

PubMed Central

Visscher, P. M.; Haley, C. S.; Thompson, R.

1996-01-01

The efficiency of marker-assisted introgression in backcross populations derived from inbred lines was investigated by simulation. Background genotypes were simulated assuming that a genetic model of many genes of small effects in coupling phase explains the observed breed difference and variance in backcross populations. Markers were efficient in introgression backcross programs for simultaneously introgressing an allele and selecting for the desired genomic background. Using a marker spacing of 10-20 cM gave an advantage of one to two backcross generations selection relative to random or phenotypic selection. When the position of the gene to be introgressed is uncertain, for example because its position was estimated from a trait gene mapping experiment, a chromosome segment should be introgressed that is likely to include the allele of interest. Even for relatively precisely mapped quantitative trait loci, flanking markers or marker haplotypes should cover ~10-20 cM around the estimated position of the gene, to ensure that the allele frequency does not decline in later backcross generations. PMID:8978075

CRISPR Primer Designer: Design primers for knockout and chromosome imaging CRISPR-Cas system.

PubMed

Yan, Meng; Zhou, Shi-Rong; Xue, Hong-Wei

2015-07-01

The clustered regularly interspaced short palindromic repeats (CRISPR)-associated system enables biologists to edit genomes precisely and provides a powerful tool for perturbing endogenous gene regulation, modulation of epigenetic markers, and genome architecture. However, there are concerns about the specificity of the system, especially the usages of knocking out a gene. Previous designing tools either were mostly built-in websites or ran as command-line programs, and none of them ran locally and acquired a user-friendly interface. In addition, with the development of CRISPR-derived systems, such as chromosome imaging, there were still no tools helping users to generate specific end-user spacers. We herein present CRISPR Primer Designer for researchers to design primers for CRISPR applications. The program has a user-friendly interface, can analyze the BLAST results by using multiple parameters, score for each candidate spacer, and generate the primers when using a certain plasmid. In addition, CRISPR Primer Designer runs locally and can be used to search spacer clusters, and exports primers for the CRISPR-Cas system-based chromosome imaging system. © 2014 Institute of Botany, Chinese Academy of Sciences.

A Diagnostic Marker to Discriminate Childhood Apraxia of Speech From Speech Delay: III. Theoretical Coherence of the Pause Marker with Speech Processing Deficits in Childhood Apraxia of Speech.

PubMed

Shriberg, Lawrence D; Strand, Edythe A; Fourakis, Marios; Jakielski, Kathy J; Hall, Sheryl D; Karlsson, Heather B; Mabie, Heather L; McSweeny, Jane L; Tilkens, Christie M; Wilson, David L

2017-04-14

Previous articles in this supplement described rationale for and development of the pause marker (PM), a diagnostic marker of childhood apraxia of speech (CAS), and studies supporting its validity and reliability. The present article assesses the theoretical coherence of the PM with speech processing deficits in CAS. PM and other scores were obtained for 264 participants in 6 groups: CAS in idiopathic, neurogenetic, and complex neurodevelopmental disorders; adult-onset apraxia of speech (AAS) consequent to stroke and primary progressive apraxia of speech; and idiopathic speech delay. Participants with CAS and AAS had significantly lower scores than typically speaking reference participants and speech delay controls on measures posited to assess representational and transcoding processes. Representational deficits differed between CAS and AAS groups, with support for both underspecified linguistic representations and memory/access deficits in CAS, but for only the latter in AAS. CAS-AAS similarities in the age-sex standardized percentages of occurrence of the most frequent type of inappropriate pauses (abrupt) and significant differences in the standardized occurrence of appropriate pauses were consistent with speech processing findings. Results support the hypotheses of core representational and transcoding speech processing deficits in CAS and theoretical coherence of the PM's pause-speech elements with these deficits.

Clinimetrics and clinical psychometrics: macro- and micro-analysis.

PubMed

Tomba, Elena; Bech, Per

2012-01-01

Clinimetrics was introduced three decades ago to specify the domain of clinical markers in clinical medicine (indexes or rating scales). In this perspective, clinical validity is the platform for selecting the various indexes or rating scales (macro-analysis). Psychometric validation of these indexes or rating scales is the measuring aspect (micro-analysis). Clinical judgment analysis by experienced psychiatrists is included in the macro-analysis and the item response theory models are especially preferred in the micro-analysis when using the total score as a sufficient statistic. Clinical assessment tools covering severity of illness scales, prognostic measures, issues of co-morbidity, longitudinal assessments, recovery, stressors, lifestyle, psychological well-being, and illness behavior have been identified. The constructive dialogue in clinimetrics between clinical judgment and psychometric validation procedures is outlined for generating developments of clinical practice in psychiatry. Copyright © 2012 S. Karger AG, Basel.

Severity of anxiety- but not depression- is associated with oxidative stress in Major Depressive Disorder.

PubMed

Steenkamp, Lisa R; Hough, Christina M; Reus, Victor I; Jain, Felipe A; Epel, Elissa S; James, S Jill; Morford, Alexandra E; Mellon, Synthia H; Wolkowitz, Owen M; Lindqvist, Daniel

2017-09-01

Oxidative stress is implicated in both depression and anxiety, but it is currently unclear whether this relates to syndromal diagnoses or trans-diagnostic dimensional symptoms. We examined the relationship between oxidative stress and severity of depression and anxiety symptoms in individuals with Major Depressive Disorder (MDD). Plasma oxidative stress markers F2-isoprostanes and oxidized glutathione (GSSG), and the antioxidant reduced glutathione (GSH), were assessed in 69 physically healthy, medication-free MDD subjects. Symptoms of anxiety and depression were assessed using the Hamilton Anxiety (HAM-A) and Hamilton Depression (HAM-D) Rating Scales. Total HAM-A and HAM-D scores, along with "core" anxiety and depression subscales, and individual HAM-D items "psychic anxiety" and "depressed mood," were related to oxidative stress markers. Analyses controlled for age, sex, BMI, and smoking. Total HAM-A ratings were positively associated with F2-isoprostanes (β=.26, p=.042) and GSSG (β=.25, p=.049), but not GSH (β=.05, p=.711). Core anxiety severity was positively associated with F2-isoprostanes (β=.34, p=.012) and GSSG, although this did not reach significance (β=.24, p=.074). None of the biological markers were significantly associated with total HAM-D or core depression ratings (all p>.13). Subjects scoring high on "psychic anxiety" had elevated F2-isoprostanes (p=.030) and GSSG (p=.020). This was not seen with "depressed mood" scores (all p>.12). We assessed peripheral oxidative markers, but their relationship to the brain is unclear. Oxidative stress is more closely related to anxiety than depression symptoms in MDD. This highlights the importance of relating oxidative stress to specific symptoms and could provide new insights into the biological correlates of affective disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

Continuous age- and sex-adjusted reference intervals of urinary markers for cerebral creatine deficiency syndromes: a novel approach to the definition of reference intervals.

PubMed

Mørkrid, Lars; Rowe, Alexander D; Elgstoen, Katja B P; Olesen, Jess H; Ruijter, George; Hall, Patricia L; Tortorelli, Silvia; Schulze, Andreas; Kyriakopoulou, Lianna; Wamelink, Mirjam M C; van de Kamp, Jiddeke M; Salomons, Gajja S; Rinaldo, Piero

2015-05-01

Urinary concentrations of creatine and guanidinoacetic acid divided by creatinine are informative markers for cerebral creatine deficiency syndromes (CDSs). The renal excretion of these substances varies substantially with age and sex, challenging the sensitivity and specificity of postanalytical interpretation. Results from 155 patients with CDS and 12 507 reference individuals were contributed by 5 diagnostic laboratories. They were binned into 104 adjacent age intervals and renormalized with Box-Cox transforms (Ξ). Estimates for central tendency (μ) and dispersion (σ) of Ξ were obtained for each bin. Polynomial regression analysis was used to establish the age dependence of both μ[log(age)] and σ[log(age)]. The regression residuals were then calculated as z-scores = {Ξ - μ[log(age)]}/σ[log(age)]. The process was iterated until all z-scores outside Tukey fences ±3.372 were identified and removed. Continuous percentile charts were then calculated and plotted by retransformation. Statistically significant and biologically relevant subgroups of z-scores were identified. Significantly higher marker values were seen in females than males, necessitating separate reference intervals in both adolescents and adults. Comparison between our reconstructed reference percentiles and current standard age-matched reference intervals highlights an underlying risk of false-positive and false-negative events at certain ages. Disease markers depending strongly on covariates such as age and sex require large numbers of reference individuals to establish peripheral percentiles with sufficient precision. This is feasible only through collaborative data sharing and the use of appropriate statistical methods. Broad application of this approach can be implemented through freely available Web-based software. © 2015 American Association for Clinical Chemistry.

Abnormal cortical sources of resting state electroencephalographic rhythms in single treatment-naïve HIV individuals: A statistical z-score index.

PubMed

Babiloni, Claudio; Pennica, Alfredo; Del Percio, Claudio; Noce, Giuseppe; Cordone, Susanna; Muratori, Chiara; Ferracuti, Stefano; Donato, Nicole; Di Campli, Francesco; Gianserra, Laura; Teti, Elisabetta; Aceti, Antonio; Soricelli, Andrea; Viscione, Magdalena; Limatola, Cristina; Andreoni, Massimo; Onorati, Paolo

2016-03-01

This study tested a simple statistical procedure to recognize single treatment-naïve HIV individuals having abnormal cortical sources of resting state delta (<4 Hz) and alpha (8-13 Hz) electroencephalographic (EEG) rhythms with reference to a control group of sex-, age-, and education-matched healthy individuals. Compared to the HIV individuals with a statistically normal EEG marker, those with abnormal values were expected to show worse cognitive status. Resting state eyes-closed EEG data were recorded in 82 treatment-naïve HIV (39.8 ys.±1.2 standard error mean, SE) and 59 age-matched cognitively healthy subjects (39 ys.±2.2 SE). Low-resolution brain electromagnetic tomography (LORETA) estimated delta and alpha sources in frontal, central, temporal, parietal, and occipital cortical regions. Ratio of the activity of parietal delta and high-frequency alpha sources (EEG marker) showed the maximum difference between the healthy and the treatment-naïve HIV group. Z-score of the EEG marker was statistically abnormal in 47.6% of treatment-naïve HIV individuals with reference to the healthy group (p<0.05). Compared to the HIV individuals with a statistically normal EEG marker, those with abnormal values exhibited lower mini mental state evaluation (MMSE) score, higher CD4 count, and lower viral load (p<0.05). This statistical procedure permitted for the first time to identify single treatment-naïve HIV individuals having abnormal EEG activity. This procedure might enrich the detection and monitoring of effects of HIV on brain function in single treatment-naïve HIV individuals. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Non-invasive Diagnosis of Fibrosis in Non-alcoholic Fatty Liver Disease

PubMed Central

Arora, Anil; Sharma, Praveen

2012-01-01

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in developed as well as in developing countries. Its prevalence continues to rise currently affecting approximately 20-30% of adults and 10% of children in the United States. Non-alcoholic fatty liver disease represents a wide spectrum of conditions ranging from fatty liver, which in general follows a benign non-progressive clinical course, to non-alcoholic steatohepatitis (NASH), a more serious form of NAFLD that may progress to cirrhosis and end-stage liver disease. Liver biopsy remains the gold standard for evaluating the degree of hepatic necroinflammation and fibrosis; however, several non-invasive investigations, such as serum biomarkers, have been developed to establish the diagnosis and also to evaluate treatment response. There has been a substantial development of non-invasive risk scores, biomarker panels, and radiological modalities to identify at risk patients with NAFLD without recourse to liver biopsy on a routine basis. Examples include combination of serum markers like NAFLD fibrosis score (NFS), BARD score, fibrometer, FIB4, and non-invasive tools like fibroscan which assess fibrosis in patients with NAFLD. Other markers of fibrosis that have been evaluated include high-sensitivity C-reactive protein, plasma pentraxin 3, interleukin-6, and cytokeratin-18. This review focuses on the methods currently available in daily clinical practice in hepatology and touches briefly on the potential future markers under investigation. PMID:25755423

Generation of marker-free Bt transgenic indica rice and evaluation of its yellow stem borer resistance.

PubMed

Kumar, S; Arul, L; Talwar, D

2010-01-01

We report on generation of marker-free (‘clean DNA’) transgenic rice (Oryza sativa), carrying minimal gene-expression-cassettes of the genes of interest, and evaluation of its resistance to yellow stem borer Scirpophaga incertulas (Lepidoptera: Pyralidae). The transgenic indica rice harbours a translational fusion of 2 different Bacillus thuringiensis (Bt) genes, namely cry1B-1Aa, driven by the green-tissue-specific phosphoenol pyruvate carboxylase (PEPC) promoter. Mature seed-derived calli of an elite indica rice cultivar Pusa Basmati-1 were co-bombarded with gene-expression-cassettes (clean DNA fragments) of the Bt gene and the marker hpt gene, to generate marker-free transgenic rice plants. The clean DNA fragments for bombardment were obtained by restriction digestion and gel extraction. Through biolistic transformation, 67 independent transformants were generated. Transformation frequency reached 3.3%, and 81% of the transgenic plants were co-transformants. Stable integration of the Bt gene was confirmed, and the insert copy number was determined by Southern analysis. Western analysis and ELISA revealed a high level of Bt protein expression in transgenic plants. Progeny analysis confirmed stable inheritance of the Bt gene according to the Mendelian (3:1) ratio. Insect bioassays revealed complete protection of transgenic plants from yellow stem borer infestation. PCR analysis of T2 progeny plants resulted in the recovery of up to 4% marker-free transgenic rice plants.

Maximization of Markers Linked in Coupling for Tetraploid Potatoes via Monoparental Haploids

PubMed Central

Bartkiewicz, Annette M.; Chilla, Friederike; Terefe-Ayana, Diro; Lübeck, Jens; Strahwald, Josef; Tacke, Eckhard; Hofferbert, Hans-Reinhard; Linde, Marcus; Debener, Thomas

2018-01-01

Haploid potato populations derived from a single tetraploid donor constitute an efficient strategy to analyze markers segregating from a single donor genotype. Analysis of marker segregation in populations derived from crosses between polysomic tetraploids is complicated by a maximum of eight segregating alleles, multiple dosages of the markers and problems related to linkage analysis of marker segregation in repulsion. Here, we present data on two monoparental haploid populations generated by prickle pollination of two tetraploid cultivars with Solanum phureja and genotyped with the 12.8 k SolCAP single nucleotide polymorphism (SNP) array. We show that in a population of monoparental haploids, the number of biallelic SNP markers segregating in linkage to loci from the tetraploid donor genotype is much larger than in putative crosses of this genotype to a diverse selection of 125 tetraploid cultivars. Although this strategy is more laborious than conventional breeding, the generation of haploid progeny for efficient marker analysis is straightforward if morphological markers and flow cytometry are utilized to select true haploid progeny. The level of introgressed fragments from S. phureja, the haploid inducer, is very low, supporting its suitability for genetic analysis. Mapping with single-dose markers allowed the analysis of quantitative trait loci (QTL) for four phenotypic traits. PMID:29868076

Simpler score of routine laboratory tests predicts liver fibrosis in patients with chronic hepatitis B.

PubMed

Zhou, Kun; Gao, Chun-Fang; Zhao, Yun-Peng; Liu, Hai-Lin; Zheng, Rui-Dan; Xian, Jian-Chun; Xu, Hong-Tao; Mao, Yi-Min; Zeng, Min-De; Lu, Lun-Gen

2010-09-01

In recent years, a great interest has been dedicated to the development of noninvasive predictive models to substitute liver biopsy for fibrosis assessment and follow-up. Our aim was to provide a simpler model consisting of routine laboratory markers for predicting liver fibrosis in patients chronically infected with hepatitis B virus (HBV) in order to optimize their clinical management. Liver fibrosis was staged in 386 chronic HBV carriers who underwent liver biopsy and routine laboratory testing. Correlations between routine laboratory markers and fibrosis stage were statistically assessed. After logistic regression analysis, a novel predictive model was constructed. This S index was validated in an independent cohort of 146 chronic HBV carriers in comparison to the SLFG model, Fibrometer, Hepascore, Hui model, Forns score and APRI using receiver operating characteristic (ROC) curves. The diagnostic values of each marker panels were better than single routine laboratory markers. The S index consisting of gamma-glutamyltransferase (GGT), platelets (PLT) and albumin (ALB) (S-index: 1000 x GGT/(PLT x ALB(2))) had a higher diagnostic accuracy in predicting degree of fibrosis than any other mathematical model tested. The areas under the ROC curves (AUROC) were 0.812 and 0.890 for predicting significant fibrosis and cirrhosis in the validation cohort, respectively. The S index, a simpler mathematical model consisting of routine laboratory markers predicts significant fibrosis and cirrhosis in patients with chronic HBV infection with a high degree of accuracy, potentially decreasing the need for liver biopsy.

Handgrip strength and associated factors in hospitalized patients.

PubMed

Guerra, Rita S; Fonseca, Isabel; Pichel, Fernando; Restivo, Maria T; Amaral, Teresa F

2015-03-01

Handgrip strength (HGS) is a marker of nutrition status. Many factors are associated with HGS. Age, height, body mass index, number of diagnoses, and number and type of drugs have been shown to modify the association between undernutrition and HGS. Nevertheless, other patient characteristics that could modify this association and its joint modifier effect have not been studied yet. To evaluate the association of inpatients' HGS and undernutrition considering the potential modifier effect of cognitive status, functional activity, disease severity, anthropometrics, and other patient characteristics on HGS. A cross-sectional study was conducted in a university hospital. Sex, age, abbreviated mental test score, functional activity score, Charlson index, number of drugs, Patient-Generated Subjective Global Assessment (PG-SGA) score, body weight, mid-arm muscle circumference, adductor pollicis muscle thickness, body height, wrist circumference, hand length, and palm width were included in a linear regression model to identify independent factors associated with HGS (dependent variable). The study sample was composed of 688 inpatients (18-91 years old). All variables included in the model were associated with HGS (β, -0.16 to 0.38; P ≤ .049) and explained 68.5% of HGS. Age, functional activity decline, Charlson index, number of drugs, PG-SGA score, body weight, and wrist circumference had a negative association with HGS. All other studied variables were positively associated with HGS. Nutrition status evaluated by PG-SGA was still associated with HGS after considering the joint effect of other patient characteristics, which reinforces the value of HGS as an indicator of undernutrition. © 2013 American Society for Parenteral and Enteral Nutrition.

A blackberry (Rubus L.) expressed sequence tag library for the development of simple sequence repeat markers

PubMed Central

Lewers, Kim S; Saski, Chris A; Cuthbertson, Brandon J; Henry, David C; Staton, Meg E; Main, Dorrie S; Dhanaraj, Anik L; Rowland, Lisa J; Tomkins, Jeff P

2008-01-01

Background The recent development of novel repeat-fruiting types of blackberry (Rubus L.) cultivars, combined with a long history of morphological marker-assisted selection for thornlessness by blackberry breeders, has given rise to increased interest in using molecular markers to facilitate blackberry breeding. Yet no genetic maps, molecular markers, or even sequences exist specifically for cultivated blackberry. The purpose of this study is to begin development of these tools by generating and annotating the first blackberry expressed sequence tag (EST) library, designing primers from the ESTs to amplify regions containing simple sequence repeats (SSR), and testing the usefulness of a subset of the EST-SSRs with two blackberry cultivars. Results A cDNA library of 18,432 clones was generated from expanding leaf tissue of the cultivar Merton Thornless, a progenitor of many thornless commercial cultivars. Among the most abundantly expressed of the 3,000 genes annotated were those involved with energy, cell structure, and defense. From individual sequences containing SSRs, 673 primer pairs were designed. Of a randomly chosen set of 33 primer pairs tested with two blackberry cultivars, 10 detected an average of 1.9 polymorphic PCR products. Conclusion This rate predicts that this library may yield as many as 940 SSR primer pairs detecting 1,786 polymorphisms. This may be sufficient to generate a genetic map that can be used to associate molecular markers with phenotypic traits, making possible molecular marker-assisted breeding to compliment existing morphological marker-assisted breeding in blackberry. PMID:18570660

Quantifying bone marrow edema in the rheumatoid cervical spine using magnetic resonance imaging.

PubMed

Suppiah, Ravi; Doyle, Anthony; Rai, Raylynne; Dalbeth, Nicola; Lobo, Maria; Braun, Jürgen; McQueen, Fiona M

2010-08-01

To determine the reliability and feasibility of a new magnetic resonance imaging (MRI) score to quantify bone marrow edema (BME), synovitis, and erosions in the cervical spine of patients with rheumatoid arthritis (RA); and to investigate the correlations among neck pain, clinical markers of RA disease activity, and MRI features of disease activity in the cervical spine. Thirty patients with RA (50% with neck pain) and a Disease Activity Score 28-joint count > 3.2 had an MRI scan of their cervical spine. STIR, VIBE, and T1-weighted postcontrast sequences were used to quantify BME. MRI scans were scored for total BME, synovitis, and erosions using a new scoring method developed by the authors and assessed for reliability and feasibility. Associations between neck pain and clinical markers of disease activity were investigated. BME was present in 14/30 patients; 9/14 (64%) had atlantoaxial BME, 10/14 (71%) had subaxial BME, and 5/14 (36%) had both. Interobserver reliability for total cervical BME score was moderate [intraclass correlation coefficient (ICC) = 0.51]. ICC improved to 0.67 if only the vertebral bodies and dens were considered. There was no correlation between neck pain or clinical measures of RA disease activity and the presence of any MRI features including BME, synovitis, or erosions. Current RA disease activity scores do not identify activity in the cervical spine. An MRI score that quantifies BME, synovitis, and erosions in the cervical spine may provide useful information regarding inflammation and damage. This could alert clinicians to the presence of significant pathology and influence management.

The power and robustness of maximum LOD score statistics.

PubMed

Yoo, Y J; Mendell, N R

2008-07-01

The maximum LOD score statistic is extremely powerful for gene mapping when calculated using the correct genetic parameter value. When the mode of genetic transmission is unknown, the maximum of the LOD scores obtained using several genetic parameter values is reported. This latter statistic requires higher critical value than the maximum LOD score statistic calculated from a single genetic parameter value. In this paper, we compare the power of maximum LOD scores based on three fixed sets of genetic parameter values with the power of the LOD score obtained after maximizing over the entire range of genetic parameter values. We simulate family data under nine generating models. For generating models with non-zero phenocopy rates, LOD scores maximized over the entire range of genetic parameters yielded greater power than maximum LOD scores for fixed sets of parameter values with zero phenocopy rates. No maximum LOD score was consistently more powerful than the others for generating models with a zero phenocopy rate. The power loss of the LOD score maximized over the entire range of genetic parameters, relative to the maximum LOD score calculated using the correct genetic parameter value, appeared to be robust to the generating models.

Comparison of cell cycle progression score with two immunohistochemical markers (PTEN and Ki-67) for predicting outcome in prostate cancer after radical prostatectomy.

PubMed

Léon, Priscilla; Cancel-Tassin, Geraldine; Drouin, Sara; Audouin, Marie; Varinot, Justine; Comperat, Eva; Cathelineau, Xavier; Rozet, François; Vaessens, Christophe; Stone, Steven; Reid, Julia; Sangale, Zaina; Korman, Patrick; Rouprêt, Morgan; Fromond-Hankard, Gaelle; Cussenot, Olivier

2018-04-20

Previous studies of the cell cycle progression (CCP) score in surgical specimens of prostate cancer (PCa) in patients treated by radical prostatectomy (RP) demonstrated significant association with time to biochemical recurrence (BCR). In this study, we compared the ability of the CCP score and the expression of PTEN or Ki-67 to predict BCR in a cohort of patients treated by RP. Finally, we constructed the best predictive model for BCR, incorporating biomarkers and relevant clinical variables. The study population consisted of 652 PCa patients enrolled in a retrospective cohort and who had RP surgery in French urological centers from 2000 to 2007. Among the 652 patients with CCP scores and complete clinical data, BCR events occurred in 41%, and the median time from surgery to the last follow-up among BCR-free patients was 72 months. In univariate Cox analysis, the continuous CCP score and positive Ki-67 predicted recurrence with a HR of 1.44 (95% CI 1.17-1.75; p = 5.3 × 10 -4 ) and 1.89 (95% CI 1.38-2.57; p = 1.6 × 10 -4 ), respectively. In contrast, PTEN expression was not associated with BCR risk. Of the three biomarkers, only the CCP score remained significantly associated in a multivariable Cox model (p = 0.026). The best model incorporated CAPRA-S and CCP scores as predictors, with HRs of 1.32 and 1.24, respectively. The CCP score was superior to the two IHC markers (PTEN and Ki-67) for predicting outcome in PCa after RP.

The sequential organ failure assessment (SOFA) score is an effective triage marker following staggered paracetamol (acetaminophen) overdose.

PubMed

Craig, D G; Zafar, S; Reid, T W D J; Martin, K G; Davidson, J S; Hayes, P C; Simpson, K J

2012-06-01

The sequential organ failure assessment (SOFA) score is an effective triage marker following single time point paracetamol (acetaminophen) overdose, but has not been evaluated following staggered (multiple supratherapeutic doses over >8 h, resulting in cumulative dose of >4 g/day) overdoses. To evaluate the prognostic accuracy of the SOFA score following staggered paracetamol overdose. Time-course analysis of 50 staggered paracetamol overdoses admitted to a tertiary liver centre. Individual timed laboratory samples were correlated with corresponding clinical parameters and the daily SOFA scores were calculated. A total of 39/50 (78%) patients developed hepatic encephalopathy. The area under the SOFA receiver operator characteristic for death/liver transplantation was 87.4 (95% CI 73.2-95.7), 94.3 (95% CI 82.5-99.1), and 98.4 (95% CI 84.3-100.0) at 0, 24 and 48 h, respectively, postadmission. A SOFA score of <6 at tertiary care admission predicted survival with a sensitivity of 100.0% (95% CI 76.8-100.0) and specificity of 58.3% (95% CI 40.8-74.5), compared with 85.7% (95% CI 60.6-97.4) and 75.0% (95% CI 65.2-79.5) , respectively, for the modified Kings College criteria. Only 2/21 patients with an admission SOFA score <6 required renal replacement therapy or intracerebral pressure monitoring. SOFA significantly outperformed the Model for End-stage Liver Disease, but not APACHE II, at 0, 24-and 48-h following admission. A SOFA score <6 at tertiary care admission following a staggered paracetamol overdose, is associated with a good prognosis. Both the SOFA and APACHE II scores could improve triage of high-risk staggered paracetamol overdose patients. © 2012 Blackwell Publishing Ltd.

Decreased fucosylated PSA as a urinary marker for high Gleason score prostate cancer.

PubMed

Fujita, Kazutoshi; Hayashi, Takuji; Matsuzaki, Kyosuke; Nakata, Wataru; Masuda, Mika; Kawashima, Atsunari; Ujike, Takeshi; Nagahara, Akira; Tsuchiya, Mutsumi; Kobayashi, Yuka; Nojima, Satoshi; Uemura, Motohide; Morii, Eiichi; Miyoshi, Eiji; Nonomura, Norio

2016-08-30

Fucosylation is an important oligosaccharide modification associated with cancer and inflammation. We investigated whether urinary fucosylated PSA (Fuc-PSA) levels could be used for the detection of high Gleason score prostate cancer. Urine samples were collected from men with abnormal digital rectal examination findings or elevated serum PSA levels, before prostate biopsy. Lectin-antibody ELISA was used to quantify the Lewis-type or core-type fucosylated PSA (PSA-AAL) and core-type fucosylated PSA (PSA-PhoSL) in the urine samples. Both types of urinary Fuc-PSA were significantly decreased in the men with prostate cancer compared with the men whose biopsies were negative for cancer (P = 0.026 and P < 0.001, respectively). Both were also significantly associated with the Gleason scores of the biopsy specimens (P = 0.001 and P < 0.001, respectively). Multivariate analysis showed that PSA density, urinary PSA-AAL, and urinary PSA-PhoSL were independent predictors of high Gleason score prostate cancer. The area under the receiver-operator characteristic curve (AUC) value for the prediction of cancers of Gleason score ≥ 7 was 0.69 for urinary PSA-AAL and 0.72 for urinary PSA-PhoSL. In contrast, the AUC value was 0.59 for serum PSA, 0.63 for PSA density, and 0.58 for urinary PSA. In conclusion, a decreased urinary Fuc-PSA level is a potential marker for the detection of high Gleason score prostate cancer.

Decreased fucosylated PSA as a urinary marker for high Gleason score prostate cancer

PubMed Central

Fujita, Kazutoshi; Hayashi, Takuji; Matsuzaki, Kyosuke; Nakata, Wataru; Masuda, Mika; Kawashima, Atsunari; Ujike, Takeshi; Nagahara, Akira; Tsuchiya, Mutsumi; Kobayashi, Yuka; Nojima, Satoshi; Uemura, Motohide; Morii, Eiichi; Miyoshi, Eiji; Nonomura, Norio

2016-01-01

Fucosylation is an important oligosaccharide modification associated with cancer and inflammation. We investigated whether urinary fucosylated PSA (Fuc-PSA) levels could be used for the detection of high Gleason score prostate cancer. Urine samples were collected from men with abnormal digital rectal examination findings or elevated serum PSA levels, before prostate biopsy. Lectin-antibody ELISA was used to quantify the Lewis-type or core-type fucosylated PSA (PSA-AAL) and core-type fucosylated PSA (PSA-PhoSL) in the urine samples. Both types of urinary Fuc-PSA were significantly decreased in the men with prostate cancer compared with the men whose biopsies were negative for cancer (P = 0.026 and P < 0.001, respectively). Both were also significantly associated with the Gleason scores of the biopsy specimens (P = 0.001 and P < 0.001, respectively). Multivariate analysis showed that PSA density, urinary PSA-AAL, and urinary PSA-PhoSL were independent predictors of high Gleason score prostate cancer. The area under the receiver-operator characteristic curve (AUC) value for the prediction of cancers of Gleason score ≥ 7 was 0.69 for urinary PSA-AAL and 0.72 for urinary PSA-PhoSL. In contrast, the AUC value was 0.59 for serum PSA, 0.63 for PSA density, and 0.58 for urinary PSA. In conclusion, a decreased urinary Fuc-PSA level is a potential marker for the detection of high Gleason score prostate cancer. PMID:27494861

Duration of high-dose aspirin therapy does not affect long-term coronary artery outcomes in Kawasaki disease.

PubMed

Migally, Karl; Braunlin, Elizabeth A; Zhang, Lei; Binstadt, Bryce A

2018-05-02

BackgroundHigh-dose aspirin (HDA) is used with intravenous immunoglobulin (IVIg) in Kawasaki disease (KD). Practice regarding HDA varies, and it is unclear whether HDA duration affects the long-term course.MethodsWe retrospectively studied KD patients at our hospital for over 10 years. Patients were categorized as having received HDA for 0, 1-7, or >7 days. Primary outcome was the maximum coronary Z-score at diagnosis and follow-up; secondary outcomes included inflammatory markers.ResultsOne hundred and three patients had HDA duration documented, of which 35 patients had coronary artery abnormalities (CAAs) at diagnosis. There was no difference in demographics or inflammatory markers between the HDA groups, and no difference in HDA duration between patients with or without CAAs. Seventeen patients received no HDA; they had longer illness and defervescence duration before diagnosis, and were less likely to receive IVIg. For CAAs, multivariate regression revealed that HDA duration did not predict the coronary Z-score at 9-15 months. Higher Z-score at diagnosis was associated with higher Z-score at 9-15 months.ConclusionThe only factor associated with coronary Z-score at 9-15 months was the Z-score at diagnosis. At our institution, longer illness and defervescence duration and the lack of IVIg administration were associated with not administering HDA. HDA duration did not affect the clinically relevant outcomes, particularly CAA persistence.Pediatric Research advance online publication, 2 May 2018; doi:10.1038/pr.2018.44.

SSCP markers provide a useful alternative to microsatellites in genotyping and estimating genetic diversity in populations and germplasm collections of plant specialty crops.

PubMed

Kuhn, David N; Motamayor, Juan Carlos; Meerow, Alan W; Borrone, James W; Schnell, Raymond J

2008-10-01

For well-studied plant species with whole genome sequence or extensive EST data, SNP markers are the logical choice for both genotyping and whole genome association studies. However, SNP markers may not address the needs of researchers working on specialty crops with limited available genomic information. Microsatellite markers have been frequently employed due to their robustness, but marker development can be difficult and may result in few polymorphic markers. SSCP markers, such as microsatellites, are PCR-based and scored by electrophoretic mobility but, because they are based on SNPs rather than length differences, occur more frequently and are easier to develop than microsatellites. We have examined how well correlated the estimation of genetic diversity and genetic distance are in a population or germplasm collection when measured by 13 highly polymorphic microsatellite markers or 20 SSCP markers. We observed a significant correlation in pairwise genetic distances of 82 individuals in an international cacao germplasm collection (Mantel test Rxy=0.59, p<0.0001 for 10 000 permutations). Both sets of markers could distinguish each individual in the population. These data provide strong support for the use of SSCP markers in the genotyping of plant species where development of microsatellites would be difficult or expensive.

Case Markers in Mongolian: A Means for Encoding Null Constituents in Noun Phrase and Relative Clause

ERIC Educational Resources Information Center

Otgonsuren, Tseden

2017-01-01

This paper focuses on the capacity of the case markers in the Mongolian language, as a relative element, to generate any finite noun phrase or relative clause based on their syntactic function or relationship. In Mongolian, there are two different approaches to generate noun phrases: parataxis and hypotaxis. According to my early observation, if…

An extension of the Maximum Lod Score method to X-linked loci.

PubMed

Cordell, H J; Kawaguchi, Y; Todd, J A; Farrall, M

1995-10-01

The Maximum Lod Score method for affected relative-pair analysis, introduced by Risch, is a powerful method for detecting linkage between an autosomal marker locus and disease. In order to use the method to detect linkage to markers on the X-chromosome, some modification is necessary. Here we extend the method to be applicable to X-chromosomal data, and derive genetic restrictions on the haplotype-sharing probabilities analogous to the 'possible triangle' restrictions described by Holmans for the autosomal case. Size criteria are derived using asymptotic theory and simulation, and the power is calculated for a number of possible underlying models. The method is applied to data from 284 type 1 diabetic families and evidence is found for the presence of one or more diabetogenic loci on the X-chromosome.

Linkage of a gene for macular corneal dystrophy to chromosome 16.

PubMed Central

Vance, J. M.; Jonasson, F.; Lennon, F.; Sarrica, J.; Damji, K. F.; Stauffer, J.; Pericak-Vance, M. A.; Klintworth, G. K.

1996-01-01

Autosomal recessive macular corneal dystrophy (MCD) is a heterogeneous disorder leading to visual impairment. Sixteen American and Icelandic families (11 type I and 5 type II) were analyzed for linkage, by use of 208 polymorphic microsatellite markers. A significant maximum LOD score Zmax of 7.82 at a maximum recombination fraction (thetamax) of .06 was found with the 16q22 locus D16S518 for MCD type I. In addition, a peak LOD score of 2.50 at a recombination fraction of .00 was obtained for the MCD type II families, by use of the identical marker. These findings raise the possibility that MCD type II may be due to the same genetic locus that is involved in MCD type I. PMID:8644739

Stress and fertility: some modalities of investigation and treatment in couples with unexplained infertility in Dublin.

PubMed

Harrison, R F; O'Moore, R R; O'Moore, A M

1986-01-01

The role of stress in infertility, and its treatment, is reviewed in various groups of couples labeled "unexplained infertile." A simplified profile of stress markers based upon basal prolactin estimations and psychological measurements found infertile couples more stressed than fertile controls and revealed a sub-group of women characterized as having significantly high psychological stress scores and intermittent elevations of prolactin (spikers). This group was effectively treated with a combination of clomiphene citrate and bromocriptine. However, attention to the failures as well as the successes suggests optimum benefit to the patients might involve not only provision of a good clinic ambiance and pharmacological preparations, but also relaxation therapies such as Autogenic Training, which significantly lowered psychological and biochemical stress marker scores.

A new method to determine wound age in early vital skin injuries: a probability scoring system using expression levels of Fibronectin, CD62p and Factor VIII in wound hemorrhage.

PubMed

van de Goot, Franklin R W; Korkmaz, H Ibrahim; Fronczek, Judith; Witte, Birgit I; Visser, Rob; Ulrich, Magda M W; Begieneman, Mark P V; Rozendaal, Lawrence; Krijnen, Paul A J; Niessen, Hans W M

2014-11-01

In forensic autopsies it is important to determine the age of early vital skin wounds as accurate as possible. In addition to inflammation, coagulation is also induced in vital wounds. Analysis of blood coagulation markers in wound hemorrhage could therefore be an important additional discriminating factor in wound age determination. The aim of this study was to develop a wound age probability scoring system, based on the immunohistochemical expression levels of Fibronectin, CD62p and Factor VIII in wound hemorrhage. Tissue samples of (A) non injured control skin (n=383), and samples of mechanically induced skin injuries of known wound age, (B) injuries inflicted shortly before death (up to a few minutes old) (n=382), and (C) injuries inflicted 15-30 min before death (n=42) were obtained at autopsy in order to validate wound age estimation. Tissue slides were stained for Fibronectin, CD62p and Factor VIII and were subsequently scored for staining intensity (IHC score) in wound hemorrhage (1=minor, 2=moderate, 3=strong positive). Finally, probability scores of these markers were calculated. In at most 14% of the non-injured control samples, hemorrhage was found, with mean±standard deviation IHC scores of 0.1±0.4, 0.2±0.4 and 0.2±0.5 for Fibronectin, CD62p, and Factor VIII, respectively. Expression of these markers significantly increased to mean IHC scores 1.4±0.8 (Fibronectin), 1.2±0.6 (CD62p), and 1.6±0.8 (Factor VIII) in wounds inflicted shortly before death (few minutes old) and to 2.6±0.5 (Fibronectin), 2.5±0.6 (CD62p), and 2.8±0.4 (Factor VIII) in 15-30 min old wounds. The probabilities that a wound was non vital in case of an IH score 0 were 87%, 88% and 90% for Fibronectin, CD62p, and Factor VIII, respectively. In case of an IHC score 1 or 2, the probabilities that a wound was a few minutes old were 82/90%, 82/83% and 72/93%. Finally, in case of an IHC score 3, the probabilities that a wound was 15-30 min old were 65%, 76% and 55%. Based on the expression of Fibronectin, CD62p and Factor VIII in wound hemorrhage, we developed a probability scoring system that can be used in forensic autopsies to improve wound age estimation in early skin injuries. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Ratios of One-Carbon Metabolites Are Functional Markers of B-Vitamin Status in a Norwegian Coronary Angiography Screening Cohort.

PubMed

Ulvik, Arve; Hustad, Steinar; McCann, Adrian; Midttun, Øivind; Nygård, Ottar K; Ueland, Per M

2017-06-01

Background: Functional (metabolic) markers of B-vitamin status, including plasma total homocysteine (tHcy) for folate and plasma methylmalonic acid (MMA) for vitamin B-12, suffer from moderate sensitivity and poor specificity. Ratios of metabolites belonging to the same pathway may have better performance characteristics. Objective: We evaluated the ratios of tHcy to total cysteine (tCys; Hcy:Cys), tHcy to creatinine (Hcy:Cre), and tHcy to tCys to creatinine (Hcy:Cys:Cre) as functional markers of B-vitamin status represented by a summary score composed of folate, cobalamin, betaine, pyridoxal 5'-phosphate (PLP), and riboflavin concentrations measured in plasma. Methods: Cross-sectional data were obtained from a cohort of patients with stable angina pectoris (2994 men and 1167 women) aged 21-88 y. The relative contribution of the B-vitamin score, age, sex, smoking, body mass index, and markers of renal function and inflammation to the variance of the functional B-vitamin markers was calculated by using multiple linear regression. Results: Compared with tHcy alone, Hcy:Cys, Hcy:Cre, and Hcy:Cys:Cre all showed improved sensitivity and specificity for detecting plasma B-vitamin status. Improvements in overall performance ranged from 4-fold for Hcy:Cys to ∼8-fold for Hcy:Cys:Cre and were particularly strong in subjects with the common 5,10-methylenetetrahydrofolate reductase (MTHFR) 677CC genotype. Conclusions: Ratios of tHcy to tCys and/or creatinine showed a severalfold improvement over tHcy alone as functional markers of B-vitamin status in Norwegian coronary angiography screenees. The biological rationale for these ratios is discussed in terms of known properties of enzymes involved in the catabolism of homocysteine and synthesis of creatine and creatinine. © 2017 American Society for Nutrition.

Sudden cardiac death and pump failure death prediction in chronic heart failure by combining ECG and clinical markers in an integrated risk model

PubMed Central

Orini, Michele; Mincholé, Ana; Monasterio, Violeta; Cygankiewicz, Iwona; Bayés de Luna, Antonio; Martínez, Juan Pablo

2017-01-01

Background Sudden cardiac death (SCD) and pump failure death (PFD) are common endpoints in chronic heart failure (CHF) patients, but prevention strategies are different. Currently used tools to specifically predict these endpoints are limited. We developed risk models to specifically assess SCD and PFD risk in CHF by combining ECG markers and clinical variables. Methods The relation of clinical and ECG markers with SCD and PFD risk was assessed in 597 patients enrolled in the MUSIC (MUerte Súbita en Insuficiencia Cardiaca) study. ECG indices included: turbulence slope (TS), reflecting autonomic dysfunction; T-wave alternans (TWA), reflecting ventricular repolarization instability; and T-peak-to-end restitution (ΔαTpe) and T-wave morphology restitution (TMR), both reflecting changes in dispersion of repolarization due to heart rate changes. Standard clinical indices were also included. Results The indices with the greatest SCD prognostic impact were gender, New York Heart Association (NYHA) class, left ventricular ejection fraction, TWA, ΔαTpe and TMR. For PFD, the indices were diabetes, NYHA class, ΔαTpe and TS. Using a model with only clinical variables, the hazard ratios (HRs) for SCD and PFD for patients in the high-risk group (fifth quintile of risk score) with respect to patients in the low-risk group (first and second quintiles of risk score) were both greater than 4. HRs for SCD and PFD increased to 9 and 11 when using a model including only ECG markers, and to 14 and 13, when combining clinical and ECG markers. Conclusion The inclusion of ECG markers capturing complementary pro-arrhythmic and pump failure mechanisms into risk models based only on standard clinical variables substantially improves prediction of SCD and PFD in CHF patients. PMID:29020031

Sudden cardiac death and pump failure death prediction in chronic heart failure by combining ECG and clinical markers in an integrated risk model.

PubMed

Ramírez, Julia; Orini, Michele; Mincholé, Ana; Monasterio, Violeta; Cygankiewicz, Iwona; Bayés de Luna, Antonio; Martínez, Juan Pablo; Laguna, Pablo; Pueyo, Esther

2017-01-01

Sudden cardiac death (SCD) and pump failure death (PFD) are common endpoints in chronic heart failure (CHF) patients, but prevention strategies are different. Currently used tools to specifically predict these endpoints are limited. We developed risk models to specifically assess SCD and PFD risk in CHF by combining ECG markers and clinical variables. The relation of clinical and ECG markers with SCD and PFD risk was assessed in 597 patients enrolled in the MUSIC (MUerte Súbita en Insuficiencia Cardiaca) study. ECG indices included: turbulence slope (TS), reflecting autonomic dysfunction; T-wave alternans (TWA), reflecting ventricular repolarization instability; and T-peak-to-end restitution (ΔαTpe) and T-wave morphology restitution (TMR), both reflecting changes in dispersion of repolarization due to heart rate changes. Standard clinical indices were also included. The indices with the greatest SCD prognostic impact were gender, New York Heart Association (NYHA) class, left ventricular ejection fraction, TWA, ΔαTpe and TMR. For PFD, the indices were diabetes, NYHA class, ΔαTpe and TS. Using a model with only clinical variables, the hazard ratios (HRs) for SCD and PFD for patients in the high-risk group (fifth quintile of risk score) with respect to patients in the low-risk group (first and second quintiles of risk score) were both greater than 4. HRs for SCD and PFD increased to 9 and 11 when using a model including only ECG markers, and to 14 and 13, when combining clinical and ECG markers. The inclusion of ECG markers capturing complementary pro-arrhythmic and pump failure mechanisms into risk models based only on standard clinical variables substantially improves prediction of SCD and PFD in CHF patients.

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

PubMed Central

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

2011-01-01

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

Prevalence of and Progression to Abnormal Non-Invasive Markers of Liver Disease (APRI and FIB-4) among US HIV-infected Youth

PubMed Central

Kapogiannis, Bill G.; Leister, Erin; Siberry, George K.; Van Dyke, Russell B.; Rudy, Bret; Flynn, Patricia; Williams, Paige L.

2015-01-01

Objective To longitudinally characterize non-invasive markers of liver disease in HIV-infected youth. Design HIV infection, without viral hepatitis co-infection, may contribute to liver disease. Non-invasive markers of liver disease [FIB-4 (Fibrosis-4) and APRI (aspartate aminotransferase-to-platelet ratio index)] have been evaluated in adults with concomitant HIV and hepatitis C, but are less studied in children. Methods In prospective cohorts of HIV-infected and HIV-uninfected youth, we used linear regression models to compare log-transformed FIB-4 and APRI measures by HIV status based on a single visit at ages 15–20 years. We also longitudinally modeled trends in these measures in HIV-infected youth with ≥2 visits to compare those with behavioral vs perinatal HIV infection (PHIV) using mixed effect linear regression, adjusting for age, gender, body mass index, and race/ethnicity. Results Of 1785 participants, 41% were male, 57% black non-Hispanic and 27% Hispanic. More HIV-infected than uninfected youth had an APRI score >0.5 (13% vs 3%, p<0.001). Among 1307 HIV-infected participants with longitudinal measures, FIB-4 scores increased 6% per year (p<0.001) among all HIV-infected youth, whereas APRI scores increased 2% per year (p=0.007) only among PHIV youth. The incidence rates (95% CI) of progression of APRI to >0.5 and >1.5 were 7.5 (6.5–8.7) and 1.4 (1.0–1.9) cases per 100 person-years of follow up, respectively. The incidence of progression of FIB-4 to >1.5 and >3.25 were 1.6 (1.2–2.2) and 0.3 (0.2–0.6) cases per 100 person-years, respectively. Conclusions APRI and FIB-4 scores were higher among HIV-infected youth. Progression to scores suggesting subclinical fibrosis or worse was common. PMID:26959353

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

Two approaches to timescale modeling for proxy series with chronological errors.

NASA Astrophysics Data System (ADS)

Divine, Dmitry; Godtliebsen, Fred

2010-05-01

A substantial part of proxy series used in paleoclimate research has chronological uncertainties. Any constructed timescale is therefore only an estimate of the true, but unknown timescale. An accurate assessment of the timing of events in the paleoproxy series and networks, as well as the use of proxy-based paleoclimate reconstructions in GCM model scoring experiments, requires the effect of these errors to be properly taken into account. We consider two types of the timescale error models corresponding to the two basic approaches to construction of the (depth-) age scale in a proxy series. Typically, a chronological control of a proxy series stemming from all types of marine and terrestrial sedimentary archives is based on the use of 14C dates, reference horizons or their combination. Depending on the prevalent origin of the available fix points (age markers) the following approaches to timescale modeling are proposed. 1) 14C dates. The algorithm uses Markov-chain Monte Carlo sampling technique to generate the ordered set of perturbed age markers. Proceeding sequentially from the youngest to the oldest fixpoint, the sampler draws random numbers from the age distribution of each individual 14C date. Every following perturbed age marker is generated such that condition of no age reversal is fulfilled. The relevant regression model is then applied to construct a simulated timescale. 2) Reference horizons (f. ex. volcanic or dust layers, T bomb peak) generally provide absolutely dated fixpoints. Due to a natural variability in sedimentation (accumulation) rate, however, the dating uncertainty in the interpolated timescale tends to grow together with a span to the nearest fixpoint. The (accumulation, sedimentation) process associated with formation of a proxy series is modelled using stochastic Levy process. The respective increments for the process are drawn from the log-normal distribution with the mean/variance ratio prescribed as a site(proxy)- dependent external parameter. The number of generated annual increments corresponds to a time interval between the considered reference horizons. The simulated series is then rescaled to match the length of the actual core section being modelled. Within each method the multitude of timescales is generated creating a number of possible realisations of a proxy series or a proxy based reconstruction in the time domain. This allows consideration of a proxy record in a probabilistic framework. The effect of accounting for uncertainties in chronology on a reconstructed environmental variable is illustrated with the two case studies of marine sediment records.

System and method for generating motion corrected tomographic images

DOEpatents

Gleason, Shaun S [Knoxville, TN; Goddard, Jr., James S.

2012-05-01

A method and related system for generating motion corrected tomographic images includes the steps of illuminating a region of interest (ROI) to be imaged being part of an unrestrained live subject and having at least three spaced apart optical markers thereon. Simultaneous images are acquired from a first and a second camera of the markers from different angles. Motion data comprising 3D position and orientation of the markers relative to an initial reference position is then calculated. Motion corrected tomographic data obtained from the ROI using the motion data is then obtained, where motion corrected tomographic images obtained therefrom.

Development and transferability of black and red raspberry microsatellite markers from short-read sequences

USDA-ARS?s Scientific Manuscript database

The advent of next-generation sequencing technologies has been a boon to the cost-effective development of molecular markers, particularly in non-model species. Here, we demonstrate the efficiency of microsatellite or simple sequence repeat (SSR) marker development from short-read sequences using th...

Chromosomal assignment of ALFP markers in upland cotton (Gossypium hirsutum L.)

USDA-ARS?s Scientific Manuscript database

In this research, we used two sets of cotton aneuploid (G. hirsutum × G. tomentosum and G. hirsutum × G. barbadense) plants to locate AFLP markers to chromosome using deletion analysis method. Thirty-eight primer combinations were used to generate 608 polymorphic AFLP markers. Ninety-eight AFLP mark...

Multiple template-based fluoroscopic tracking of lung tumor mass without implanted fiducial markers

NASA Astrophysics Data System (ADS)

Cui, Ying; Dy, Jennifer G.; Sharp, Gregory C.; Alexander, Brian; Jiang, Steve B.

2007-10-01

Precise lung tumor localization in real time is particularly important for some motion management techniques, such as respiratory gating or beam tracking with a dynamic multi-leaf collimator, due to the reduced clinical tumor volume (CTV) to planning target volume (PTV) margin and/or the escalated dose. There might be large uncertainties in deriving tumor position from external respiratory surrogates. While tracking implanted fiducial markers has sufficient accuracy, this procedure may not be widely accepted due to the risk of pneumothorax. Previously, we have developed a technique to generate gating signals from fluoroscopic images without implanted fiducial markers using a template matching method (Berbeco et al 2005 Phys. Med. Biol. 50 4481-90, Cui et al 2007 Phys. Med. Biol. 52 741-55). In this paper, we present an extension of this method to multiple-template matching for directly tracking the lung tumor mass in fluoroscopy video. The basic idea is as follows: (i) during the patient setup session, a pair of orthogonal fluoroscopic image sequences are taken and processed off-line to generate a set of reference templates that correspond to different breathing phases and tumor positions; (ii) during treatment delivery, fluoroscopic images are continuously acquired and processed; (iii) the similarity between each reference template and the processed incoming image is calculated; (iv) the tumor position in the incoming image is then estimated by combining the tumor centroid coordinates in reference templates with proper weights based on the measured similarities. With different handling of image processing and similarity calculation, two such multiple-template tracking techniques have been developed: one based on motion-enhanced templates and Pearson's correlation score while the other based on eigen templates and mean-squared error. The developed techniques have been tested on six sequences of fluoroscopic images from six lung cancer patients against the reference tumor positions manually determined by a radiation oncologist. The tumor centroid coordinates automatically detected using both methods agree well with the manually marked reference locations. The eigenspace tracking method performs slightly better than the motion-enhanced method, with average localization errors less than 2 pixels (1 mm) and the error at a 95% confidence level of about 2-4 pixels (1-2 mm). This work demonstrates the feasibility of direct tracking of a lung tumor mass in fluoroscopic images without implanted fiducial markers using multiple reference templates.

Autonomic Dysfunction Correlates with Clinical and Inflammatory Activity in Patients with Crohn's Disease.

PubMed

Engel, Tal; Ben-Horin, Shomron; Beer-Gabel, Marc

2015-10-01

Autonomic dysfunction has been implicated in Crohn's disease (CD). We aimed to investigate heart rate variability (HRV) as a marker of possible autonomic imbalance in patients with CD. Thirty patients with CD and 30 age- and gender-matched healthy controls were enrolled in a prospective cohort study and underwent HRV study. Anxiety level was scored using the STAI questionnaire and CD clinical activity was assessed by Harvey-Bradshaw index. Blood tests including inflammatory markers were obtained for all participants. CD subjects had lower mean blood pressure (85.51 ± 11.07 mm Hg, 91.51 ± 6.99, P = 0.015) and albumin and significantly higher CRP and IL-6 compared with controls (P < 0.002 for all comparisons). Mean HRV values of very low-frequency power and low-frequency power components were significantly lower among CD subjects (P = 0.038 and 0.027, respectively), implying a predominant sympathetic tone. Anxiety level scores were significantly higher among patients with CD for both state anxiety (P = 0.001) and trait anxiety (P < 0.0001). However, patients with active disease had similar anxiety scores as patients in remission, yet had a significantly lower BMI, lower albumin level, and higher CRP and IL-6 levels (P < 0.05 for all comparisons). Moreover, despite similar anxiety scores, patients with active disease had higher pulse rate (P = 0.02) and lower HRV indexes, which correlated with albumin levels(r = 0.7, P = 0.001). Although patients with CD have higher anxiety levels compared with controls, they exhibit depressed HRV independent of this anxiety state and in direct correlation with disease activity and inflammatory markers. These observations suggest an inherent imbalance of autonomic function associated with active inflammation.

Muscle strength and physical performance as predictors of mortality, hospitalization, and disability in the oldest old.

PubMed

Legrand, Delphine; Vaes, Bert; Matheï, Catharina; Adriaensen, Wim; Van Pottelbergh, Gijs; Degryse, Jean-Marie

2014-06-01

To evaluate the predictive value of muscle strength and physical performance in the oldest old for all-cause mortality; hospitalization; and the onset of disability, defined as a decline in activities of daily living (ADLs), independent of muscle mass, inflammatory markers, and comorbidities. A prospective, observational, population-based follow-up study. Three well-circumscribed areas of Belgium. Five hundred sixty participants aged 80 and older were followed for 33.5 months (interquartile range 31.1-35.6 months). Grip strength, Short Physical Performance Battery (SPPB) score, and muscle mass were measured at baseline; ADLs at baseline and after 20 months; and all-cause mortality and time to first hospitalization from inclusion onward. Kaplan-Meier curves and Cox proportional hazards models were calculated for all-cause mortality and hospitalization. Logistic regression analysis was used to determine predictors of decline in ADLs. Kaplan-Meier curves showed significantly higher all-cause mortality and hospitalization in subjects in the lowest tertile of grip strength and SPPB score. The adjusted Cox proportional hazards model showed that participants with high grip strength or a high SPPB score had a lower risk of mortality and hospitalization, independent of muscle mass, inflammatory markers, and comorbidity. A relationship was found between SPPB score and decline in ADLs, independent of muscle mass, inflammation, and comorbidity. In people aged 80 and older, physical performance is a strong predictor of mortality, hospitalization, and disability, and muscle strength is a strong predictor of mortality and hospitalization. All of these relationships were independent of muscle mass, inflammatory markers, and comorbidity. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

Fascin and EMMPRIN expression in primary mucinous tumors of ovary: a tissue microarray study.

PubMed

Alici, Omer; Kefeli, Mehmet; Yildiz, Levent; Baris, Sancar; Karagoz, Filiz; Kandemir, Bedri

2014-12-01

The aim of this study was to compare the expressions of fascin and EMMPRIN in primary malignant, borderline and benign mucinous ovarian tumors, and to investigate the relationship of these markers with tumor progression and their applicability to differential diagnosis. An immunohistochemical study was performed for fascin and EMMPRIN using the tissue microarray technique. Eighty-one cases were included in the study; there were 37 benign, 25 borderline and 19 malignant primary mucinous ovarian tumors. For each case, a total staining score was determined, consisting of scores for extent of staining and intensity of staining. The cases were allocated to negative, weakly positive and strongly positive staining categories, according to the total staining score. Both of the markers were significantly negative in benign tumors as compared with borderline and malignant tumors. There was no significant difference between borderline and malignant groups for both markers. Sixty-eight percent of malignant tumors were stained positive by fascin, while this rate was 40% for borderline mucinous tumors. All malignant tumors were strongly stained positive for EMMPRIN, while this rate was 92% for borderline mucinous tumors. The rest of the cases stained weakly positive. No significant difference in staining score was found between fascin and EMMPRIN expression. In ovarian primary mucinous tumors, fascin and EMMPRIN may play an important role in tumor progression from benign tumor to carcinoma. In that context, EMMPRIN and fascin expression may have potential application in the differential diagnosis of some diagnostically problematic mucinous ovarian tumors. However, the differential diagnostic applicability of EMMPRIN appears to be more limited than that of fascin due to its wide spectrum of staining in mucinous ovarian tumors. Copyright © 2014 Elsevier GmbH. All rights reserved.

CD-163 correlated with symptoms (pain or discomfort) of prostatic inflammation.

PubMed

Yamamichi, Fukashi; Shigemura, Katsumi; Arakawa, Soichi; Tanaka, Kazushi; Fujisawa, Masato

2015-01-01

The purpose of this study is to identify significant immune-system related for symptom of patients with prostatic inflammation in order to investigate the etiology of prostatic inflammation which may relate to potentially chronic prostatitis (CP). We investigated the expression of immune system-related biomarkers such as Interleukin (IL) -6 (humoral immunity), CD-3 (T-lymphocyte), and CD-163 (macrophage) in prostate biopsy (PBx) specimens from patients with prostatic inflammation (without cancer) which had been neither clinically diagnosed benign prostatic hyperplasia nor chronic prostatitis. We examined the correlation between these markers' expressions and the symptom scores using the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), International Prostate Symptom Score (IPSS)/quality of life (QOL) which are the index for lower urinary tract symptoms (LUTS). Our results showed CD-163 (macrophage) reflected pain or discomfort on NIH-CPSI scores (P=0.0389 and r=0.3307) in the patients with prostatic inflammation; however, the control patients had no significant correlation between symptom scores and those immune-related markers' expression. These results suggest that pain or discomfort related to macrophages in the relationship between immune-system and the symptom of prostatic inflammation. In conclusion, CD-163, related to immune-system (macrophage), correlated with symptoms (pain or discomfort) of prostatic inflammation and might represent a significant immune-system related biomarker for pain or LUTS score in potentially CP.

Prediction of the effect of atrasentan on renal and heart failure outcomes based on short-term changes in multiple risk markers.

PubMed

Schievink, Bauke; de Zeeuw, Dick; Smink, Paul A; Andress, Dennis; Brennan, John J; Coll, Blai; Correa-Rotter, Ricardo; Hou, Fan Fan; Kohan, Donald; Kitzman, Dalane W; Makino, Hirofumi; Parving, Hans-Henrik; Perkovic, Vlado; Remuzzi, Giuseppe; Tobe, Sheldon; Toto, Robert; Hoekman, Jarno; Lambers Heerspink, Hiddo J

2016-05-01

A recent phase II clinical trial (Reducing Residual Albuminuria in Subjects with Diabetes and Nephropathy with AtRasentan trial and an identical trial in Japan (RADAR/JAPAN)) showed that the endothelin A receptor antagonist atrasentan lowers albuminuria, blood pressure, cholesterol, hemoglobin, and increases body weight in patients with type 2 diabetes and nephropathy. We previously developed an algorithm, the Parameter Response Efficacy (PRE) score, which translates short-term drug effects into predictions of long-term effects on clinical outcomes. We used the PRE score on data from the RADAR/JAPAN study to predict the effect of atrasentan on renal and heart failure outcomes. We performed a post-hoc analysis of the RADAR/JAPAN randomized clinical trials in which 211 patients with type-2 diabetes and nephropathy were randomly assigned to atrasentan 0.75 mg/day, 1.25 mg/day, or placebo. A PRE score was developed in a background set of completed clinical trials using multivariate Cox models. The score was applied to baseline and week-12 risk marker levels of RADAR/JAPAN participants, to predict atrasentan effects on clinical outcomes. Outcomes were defined as doubling serum creatinine or end-stage renal disease and hospitalization for heart failure. The PRE score predicted renal risk changes of -23% and -30% for atrasentan 0.75 and 1.25 mg/day, respectively. PRE scores also predicted a small non-significant increase in heart failure risk for atrasentan 0.75 and 1.25 mg/day (+2% vs. +7%). Selecting patients with >30% albuminuria reduction from baseline (responders) improved renal outcome to almost 50% risk reduction, whereas non-responders showed no renal benefit. Based on the RADAR/JAPAN study, with short-term changes in risk markers, atrasentan is expected to decrease renal risk without increased risk of heart failure. Within this population albuminuria responders appear to contribute to the predicted improvements, whereas non-responders showed no benefit. The ongoing hard outcome trial (SONAR) in type 2 diabetic patients with >30% albuminuria reduction to atrasentan will allow us to assess the validity of these predictions. © The European Society of Cardiology 2015.

A novel Acute Retroviral Syndrome Severity Score predicts the key surrogate markers for HIV-1 disease progression.

PubMed

Braun, Dominique L; Kouyos, Roger; Oberle, Corinna; Grube, Christina; Joos, Beda; Fellay, Jacques; McLaren, Paul J; Kuster, Herbert; Günthard, Huldrych F

2014-01-01

Best long-term practice in primary HIV-1 infection (PHI) remains unknown for the individual. A risk-based scoring system associated with surrogate markers of HIV-1 disease progression could be helpful to stratify patients with PHI at highest risk for HIV-1 disease progression. We prospectively enrolled 290 individuals with well-documented PHI in the Zurich Primary HIV-1 Infection Study, an open-label, non-randomized, observational, single-center study. Patients could choose to undergo early antiretroviral treatment (eART) and stop it after one year of undetectable viremia, to go on with treatment indefinitely, or to defer treatment. For each patient we calculated an a priori defined "Acute Retroviral Syndrome Severity Score" (ARSSS), consisting of clinical and basic laboratory variables, ranging from zero to ten points. We used linear regression models to assess the association between ARSSS and log baseline viral load (VL), baseline CD4+ cell count, and log viral setpoint (sVL) (i.e. VL measured ≥90 days after infection or treatment interruption). Mean ARSSS was 2.89. CD4+ cell count at baseline was negatively correlated with ARSSS (p = 0.03, n = 289), whereas HIV-RNA levels at baseline showed a strong positive correlation with ARSSS (p<0.001, n = 290). In the regression models, a 1-point increase in the score corresponded to a 0.10 log increase in baseline VL and a CD4+ cell count decline of 12/µl, respectively. In patients with PHI and not undergoing eART, higher ARSSS were significantly associated with higher sVL (p = 0.029, n = 64). In contrast, in patients undergoing eART with subsequent structured treatment interruption, no correlation was found between sVL and ARSSS (p = 0.28, n = 40). The ARSSS is a simple clinical score that correlates with the best-validated surrogate markers of HIV-1 disease progression. In regions where ART is not universally available and eART is not standard this score may help identifying patients who will profit the most from early antiretroviral therapy.

Markers of epithelial-to-mesenchymal transition reflect tumor biology according to patient age and Gleason score in prostate cancer

PubMed Central

Jędroszka, Dorota; Hamouz, Raneem; Górniak, Karolina; Bednarek, Andrzej K.

2017-01-01

Introduction Prostate carcinoma (PRAD) is one of the most frequently diagnosed malignancies amongst men worldwide. It is well-known that androgen receptor (AR) plays a pivotal role in a vast majority of prostate tumors. However, recent evidence emerged stating that estrogen receptors (ERs) may also contribute to prostate tumor development. Moreover, progression and aggressiveness of prostate cancer may be associated with differential expression genes of epithelial-to-mesenchymal transition (EMT). Therefore we aimed to assess the significance of receptors status as well as EMT marker genes expression among PRAD patients in accordance to their age and Gleason score. Materials and methods We analyzed TCGA gene expression profiles of 497 prostate tumor samples according to 43 genes involved in EMT and 3 hormone receptor genes (AR, ESR1, ESR2) as well as clinical characteristic of cancer patients. Then patients were divided into four groups according to their age and 5 groups according to Gleason score. Next, we evaluated PRAD samples according to relationship between the set of variables in different combinations and compared differential expression in subsequent groups of patients. The analysis was applied using R packages: FactoMineR, gplots, RColorBrewer and NMF. Results MFA analysis resulted in distinct grouping of PRAD patients into four age categories according to expression level of AR, ESR1 and ESR2 with the most distinct group of age less than 50 years old. Further investigations indicated opposite expression profiles of EMT markers between different age groups as well as strong association of EMT gene expression with Gleason score. We found that depending on age of prostate cancer patients and Gleason score EMT genes with distinctly altered expression are: KRT18, KRT19, MUC1 and COL4A1, CTNNB1, SNAI2, ZEB1 and MMP3. Conclusions Our major observation is that prostate cancer from patients under 50 years old compared to older ones has entirely different EMT gene expression profiles showing potentially more aggressive invasive phenotype, despite Gleason score classification. PMID:29206234

Markers of epithelial-to-mesenchymal transition reflect tumor biology according to patient age and Gleason score in prostate cancer.

PubMed

Jędroszka, Dorota; Orzechowska, Magdalena; Hamouz, Raneem; Górniak, Karolina; Bednarek, Andrzej K

2017-01-01

Prostate carcinoma (PRAD) is one of the most frequently diagnosed malignancies amongst men worldwide. It is well-known that androgen receptor (AR) plays a pivotal role in a vast majority of prostate tumors. However, recent evidence emerged stating that estrogen receptors (ERs) may also contribute to prostate tumor development. Moreover, progression and aggressiveness of prostate cancer may be associated with differential expression genes of epithelial-to-mesenchymal transition (EMT). Therefore we aimed to assess the significance of receptors status as well as EMT marker genes expression among PRAD patients in accordance to their age and Gleason score. We analyzed TCGA gene expression profiles of 497 prostate tumor samples according to 43 genes involved in EMT and 3 hormone receptor genes (AR, ESR1, ESR2) as well as clinical characteristic of cancer patients. Then patients were divided into four groups according to their age and 5 groups according to Gleason score. Next, we evaluated PRAD samples according to relationship between the set of variables in different combinations and compared differential expression in subsequent groups of patients. The analysis was applied using R packages: FactoMineR, gplots, RColorBrewer and NMF. MFA analysis resulted in distinct grouping of PRAD patients into four age categories according to expression level of AR, ESR1 and ESR2 with the most distinct group of age less than 50 years old. Further investigations indicated opposite expression profiles of EMT markers between different age groups as well as strong association of EMT gene expression with Gleason score. We found that depending on age of prostate cancer patients and Gleason score EMT genes with distinctly altered expression are: KRT18, KRT19, MUC1 and COL4A1, CTNNB1, SNAI2, ZEB1 and MMP3. Our major observation is that prostate cancer from patients under 50 years old compared to older ones has entirely different EMT gene expression profiles showing potentially more aggressive invasive phenotype, despite Gleason score classification.

Microsatellite loci discovery from next-generation sequencing data and loci characterization in the epizoic barnacle Chelonibia testudinaria (Linnaeus, 1758)

PubMed Central

Zardus, John D.; Wares, John P.

2016-01-01

Microsatellite markers remain an important tool for ecological and evolutionary research, but are unavailable for many non-model organisms. One such organism with rare ecological and evolutionary features is the epizoic barnacle Chelonibia testudinaria (Linnaeus, 1758). Chelonibia testudinaria appears to be a host generalist, and has an unusual sexual system, androdioecy. Genetic studies on host specificity and mating behavior are impeded by the lack of fine-scale, highly variable markers, such as microsatellite markers. In the present study, we discovered thousands of new microsatellite loci from next-generation sequencing data, and characterized 12 loci thoroughly. We conclude that 11 of these loci will be useful markers in future ecological and evolutionary studies on C. testudinaria. PMID:27231653

Replication of a Genome-Wide Association Study of Birth Weight in Preterm Neonates

PubMed Central

Ryckman, Kelli K; Feenstra, Bjarke; Shaffer, John R.; Bream, Elise NA; Geller, Frank; Feingold, Eleanor; Weeks, Daniel E; Gadow, Enrique; Cosentino, Viviana; Saleme, Cesar; Simhan, Hyagriv N; Merrill, David; Fong, Chin-To; Busch, Tamara; Berends, Susan K; Comas, Belen; Camelo, Jorge L; Boyd, Heather; Laurie, Cathy; Crosslin, David; Zhang, Qi; Doheny, Kim F; Pugh, Elizabeth; Melbye, Mads; Marazita, Mary L; Dagle, John M; Murray, Jeffrey C

2011-01-01

Objective To examine associations in a preterm population between rs9883204 in ADCY5 and rs900400 near LEKR1 and CCNL1 with birth weight. Both markers were associated with birth weight in a term population in a recent genome-wide association (GWA) study by Freathy et al. Study design A meta-analysis of mother and infant samples was performed for associations of rs900400 and rs9883204 with birth weight in 393 families from the U.S., 265 families from Argentina and 735 mother-infant pairs from Denmark. Z scores adjusted for infant sex and gestational age were generated for each population separately and regressed on allele counts. Association evidence was combined across sites by inverse-variance weighted meta-analysis. Results Each additional C allele of rs900400 (LEKR1/CCNL1) in infants was marginally associated with a 0.069 standard deviation (SD) lower birth weight (95% CI = −0.159 – 0.022, P = 0.068). This result was slightly more pronounced after adjusting for smoking (P = 0.036). There were no significant associations identified with rs9883204 or in maternal samples. Conclusions These results indicate the potential importance of this marker on birth weight irrespective of gestational age. PMID:21885063

Progressive sutural cataract associated with a BFSP2 mutation in a Chinese family.

PubMed

Zhang, Lu; Gao, Linghan; Li, Zhijian; Qin, Wei; Gao, Weiqi; Cui, Xiaobo; Feng, Guoyin; Fu, Songbin; He, Lin; Liu, Ping

2006-12-20

To identify the mutation underlying the segregation of progressive sutural congenital cataracts in a four-generation Chinese pedigree. Genomic DNA was extracted from the peripheral blood samples of members of the pedigree. A genome-wide scan was performed using microsatellite markers spaced at about 10 cM intervals. Linkage analysis was carried out using a Linkage software package. Ten additional microsatellite markers for the positive region were selected for precise targeting, and haplotype data were processed using Cyrillic software to define the region of the disease gene. Mutation detection was carried out by sequencing candidate genes. Significant evidence of linkage was obtained at marker D3S1279 (LOD score [Z] =2.32, recombination fraction [theta]=0.0). Precise targeting and haplotype analysis traced the disease gene to a 38.6 cM region bounded by D3S1267 and D3S1614 at 3q21.1- q26.2 near BFSP2, which encodes a lens-specific beaded filament protein. Sequencing results revealed a 3-bp deletion of nucleotides 696-698 (GAA) in exon 3 of BFSP2, which is predicted to cause an in-frame deletion of glutamic acid residue 233 from the polypeptide encoded by the mutant gene. This deletion was seen neither in any unaffected member of the family nor in 50 unrelated control individuals. We observed progressive isolated sutural cataract associated with a deletion mutation of the BFSP2 gene in a Chinese pedigree. It highlights the physiological importance of the beaded filament protein and supports the role of BFSP2 in human cataract formation.

Body fat distribution, metabolic and inflammatory markers and retinal microvasculature in school-age children. The Generation R Study.

PubMed

Gishti, O; Jaddoe, V W V; Hofman, A; Wong, T Y; Ikram, M K; Gaillard, R

2015-10-01

To examine the associations of body fatness, metabolic and inflammatory markers with retinal vessel calibers among children. We performed a population-based cohort study among 4145 school-age children. At the median age of 6.0 years (95% range 5.8, 8.0 years), we measured body mass index, total and abdominal fat mass, metabolic and inflammatory markers (blood levels of lipids, insulin and C-peptide and C-reactive protein) and retinal vascular calibers from retinal photographs. We observed that compared with normal weight children, obese children had narrower retinal arteriolar caliber (difference -0.21 s.d. score (SDS; 95% confidence interval (CI) -0.35, -0.06)), but not venular caliber. Continuous analyses showed that higher body mass index and total body fat mass, but not android/gynoid fat mass ratio and pre-peritoneal fat mass, were associated with narrower retinal arteriolar caliber (P<0.05 for body mass index and total body fat mass), but not with retinal venular caliber. Lipid and insulin levels were not associated with retinal vessel calibers. Higher C-reactive protein was associated with only wider retinal venular caliber (difference 0.10 SDS (95% CI 0.06, 0.14) per SDS increase in C-reactive protein). This latter association was not influenced by body mass index. Higher body fatness is associated with narrower retinal arteriolar caliber, whereas increased C-reactive protein levels are associated with wider retinal venular caliber. Increased fat mass and inflammation correlate with microvascular development from school-age onwards.

A new locus on 3p23–p25 for an autosomal-dominant limb-girdle muscular dystrophy, LGMD1H

PubMed Central

Bisceglia, Luigi; Zoccolella, Stefano; Torraco, Alessandra; Piemontese, Maria Rosaria; Dell'Aglio, Rosa; Amati, Angela; De Bonis, Patrizia; Artuso, Lucia; Copetti, Massimiliano; Santorelli, Filippo Maria; Serlenga, Luigi; Zelante, Leopoldo; Bertini, Enrico; Petruzzella, Vittoria

2010-01-01

Limb-girdle muscular dystrophies (LGMDs) are a genetically heterogeneous group of neuromuscular disorders with a selective or predominant involvement of shoulder and pelvic girdles. We clinically examined 19 members in a four-generation Italian family with autosomal-dominant LGMD. A total of 11 subjects were affected. Clinical findings showed variable expressivity in terms of age at onset and disease severity. Five subjects presented with a slowly progressive proximal muscle weakness, in both upper and lower limbs, with onset during the fourth–fifth decade of life, which fulfilled the consensus diagnostic criteria for LGMD. Earlier onset of the disease was observed in a group of patients presenting with muscle weakness and/or calf hypertrophy, and/or occasionally high CK and lactate serum levels. Two muscle biopsies showed morphological findings compatible with MD associated with subsarcolemmal accumulation of mitochondria and the presence of multiple mitochondrial DNA deletions. A genome-wide scan performed using microsatellite markers mapped the disease on chromosome 3p23–p25.1 locus in a 25-cM region between markers D3S1263 and D3S3685. The highest two-point LOD score was 3.26 (θ=0) at marker D3S1286 and D3S3613, whereas non-parametric analysis reached a P-value=0.0004. Four candidate genes within the refined region were analysed but did not reveal any mutations. Our findings further expand the clinical and genetic heterogeneity of LGMDs. PMID:20068593

Evaluating a 4-marker signature of aggressive prostate cancer using time-dependent AUC.

PubMed

Gerke, Travis A; Martin, Neil E; Ding, Zhihu; Nuttall, Elizabeth J; Stack, Edward C; Giovannucci, Edward; Lis, Rosina T; Stampfer, Meir J; Kantoff, Phillip W; Parmigiani, Giovanni; Loda, Massimo; Mucci, Lorelei A

2015-12-01

We previously identified a protein tumor signature of PTEN, SMAD4, SPP1, and CCND1 that, together with clinical features, was associated with lethal outcomes among prostate cancer patients. In the current study, we sought to validate the molecular model using time-dependent measures of AUC and predictive values for discriminating lethal from non-lethal prostate cancer. Using data from the initial study, we fit survival models for men with prostate cancer who were participants in the Physicians' Health Study (PHS; n = 276). Based on these models, we generated prognostic risk scores in an independent population, the Health Professionals Follow-up Study (HPFS; n = 347) to evaluate external validity. In each cohort, men were followed prospectively from cancer diagnosis through 2011 for development of distant metastasis or cancer mortality. We measured protein tumor expression of PTEN, SMAD4, SPP1, and CCND1 on tissue microarrays. During a median of 11.9 and 14.3 years follow-up in the PHS and HPFS cohorts, 24 and 32 men (9%) developed lethal disease. When used as a prognostic factor in a new population, addition of the four markers to clinical variables did not improve discriminatory accuracy through 15 years of follow-up. Although the four markers have been identified as key biological mediators in metastatic progression, they do not provide independent, long-term prognostic information beyond clinical factors when measured at diagnosis. This finding may underscore the broad heterogeneity in aggressive prostate tumors and highlight the challenges that may result from overfitting in discovery-based research. © 2015 Wiley Periodicals, Inc.

Usefulness of p16ink4a, ProEX C, and Ki-67 for the diagnosis of glandular dysplasia and adenocarcinoma of the cervix uteri.

PubMed

Negri, Giovanni; Bellisano, Giulia; Carico, Elisabetta; Faa, Gavino; Kasal, Armin; Antoniazzi, Sonia; Egarter-Vigl, Eduard; Piccin, Andrea; Dalla Palma, Paolo; Vittadello, Fabio

2011-07-01

Although the diagnostic criteria of in-situ and invasive adenocarcinomas of the cervix uteri are well established, the differentiation from benign mimics may be difficult and the morphologic features of the precursors of endocervical adenocarcinoma are still debated. In this study, we evaluated the usefulness of p16ink4a (p16), ProEX C, and Ki-67 for the diagnosis of endocervical adenocarcinoma and its precursors. Immunohistochemistry with p16, ProEX C, and Ki-67 was performed in 82 glandular lesions including 15 invasive adenocarcinomas, 29 adenocarcinomas in situ (AIS), 22 non-neoplastic samples, and 16 cases of glandular dysplasia (GD), which showed significant nuclear abnormalities but did not meet the diagnostic criteria for AIS. The immunohistochemical expression pattern was scored according to the percentage of the stained cells (0, 1+, 2+, and 3+ when 0% to 5%, 6% to 25%, 26% to 50%, and more than 50% of the cells were stained, respectively) and was evaluated for each antibody. p16 was at least focally expressed (1+ or more) in 14 of 15 invasive adenocarcinomas, in all AIS and in 7 negative samples. ProEX C and Ki-67 both scored 1+ or more in all adenocarcinomas and AIS and in 8 and 6 negative samples, respectively. Of the GD 15, 14, and 15 expressed p16, ProEX C, and Ki-67, respectively. The score differences between neoplastic and non-neoplastic samples were highly significant for each marker (P<0.001); however, the score distribution by marker differed significantly only in GD (P=0.006) in which, compared with the other markers, p16 showed more often a 3+ pattern. Our study shows that p16, Ki-67, and ProEX C may be helpful for the diagnosis of glandular lesions of the cervix uteri and may also improve the diagnostic accuracy of endocervical GD. In particularly problematic cases, the combination of p16 and a proliferation marker can provide additional help for the interpretation of these lesions.

A family of LRR sequences in the vicinity of the Co-2 locus for anthracnose resistance in Phaseolus vulgaris and its potential use in marker-assisted selection.

PubMed

Geffroy, V; Creusot, F; Falquet, J; Sévignac, M; Adam-Blondon, A F; Bannerot, H; Gepts, P; Dron, M

1998-03-01

Molecular markers offer new opportunities for breeding for disease resistance. Resistance gene pyramiding in a single cultivar, as a strategy for durable resistance, can be facilitated by marker-assisted selection (MAS). A RAPD marker, ROH20(450), linked to the Mesoamerican Co-2 anthracnose resistance gene, was previously transformed into a SCAR marker, SCH20. In the present paper we have further characterized the relevance of the SCH20 SCAR marker in different genetic backgrounds. Since this SCAR marker was found to be useful mainly in the Andean gene pool, we identified a new PCR-based marker (SCAreoli) for indirect scoring of the presence of the Co-2 gene. The SCAreoli SCAR marker is polymorphic in the Mesoamerican as well as in the Andean gene pool and should be useful in MAS. We also report that PvH20, the cloned sequence corresponding to the 450-bp RAPD marker ROH20(450), contains six imperfect leucine-rich repeats, and reveals a family of related sequences in the vicinity of the Co-2 locus. These results are discussed in the context of the recent cloning of some plant resistance genes.

Molecular markers for urothelial bladder cancer prognosis: toward implementation in clinical practice.

PubMed

van Rhijn, Bas W G; Catto, James W; Goebell, Peter J; Knüchel, Ruth; Shariat, Shahrokh F; van der Poel, Henk G; Sanchez-Carbayo, Marta; Thalmann, George N; Schmitz-Dräger, Bernd J; Kiemeney, Lambertus A

2014-10-01

To summarize the current status of clinicopathological and molecular markers for the prediction of recurrence or progression or both in non-muscle-invasive and survival in muscle-invasive urothelial bladder cancer, to address the reproducibility of pathology and molecular markers, and to provide directions toward implementation of molecular markers in future clinical decision making. Immunohistochemistry, gene signatures, and FGFR3-based molecular grading were used as molecular examples focussing on prognostics and issues related to robustness of pathological and molecular assays. The role of molecular markers to predict recurrence is limited, as clinical variables are currently more important. The prediction of progression and survival using molecular markers holds considerable promise. Despite a plethora of prognostic (clinical and molecular) marker studies, reproducibility of pathology and molecular assays has been understudied, and lack of reproducibility is probably the main reason that individual prediction of disease outcome is currently not reliable. Molecular markers are promising to predict progression and survival, but not recurrence. However, none of these are used in the daily clinical routine because of reproducibility issues. Future studies should focus on reproducibility of marker assessment and consistency of study results by incorporating scoring systems to reduce heterogeneity of reporting. This may ultimately lead to incorporation of molecular markers in clinical practice. Copyright © 2014 Elsevier Inc. All rights reserved.

Complete genomic screen in late-onset familial Alzheimer disease. Evidence for a new locus on chromosome 12.

PubMed

Pericak-Vance, M A; Bass, M P; Yamaoka, L H; Gaskell, P C; Scott, W K; Terwedow, H A; Menold, M M; Conneally, P M; Small, G W; Vance, J M; Saunders, A M; Roses, A D; Haines, J L

1997-10-15

Four genetic loci have been identified as contributing to Alzheimer disease (AD), including the amyloid precursor protein gene, the presenilin 1 gene, the presenilin 2 gene, and the apolipoprotein E gene, but do not account for all the genetic risk for AD. To identify additional genetic risk factors for late-onset AD. A complete genomic screen was performed (N=280 markers). Critical values for chromosomal regional follow-up were a P value of .05 or less for affected relative pair analysis or sibpair analysis, a parametric lod score of 1.0 or greater, or both. Regional follow-up included analysis of additional markers and a second data set. Clinic populations in the continental United States. From a series of multiplex families affected with late-onset (> or =60 years) AD ascertained during the last 14 years (National Insititute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association diagnostic criteria) and for which DNA has been obtained, a subset of 16 families (135 total family members, 52 of whom were patients with AD) was used for the genomic screen. A second subset of 38 families (216 total family members, 89 of whom were patients with AD) was used for the follow-up analysis. Linkage analysis results generated using both genetic model-dependent (lod score) and model-independent methods. Fifteen chromosomal regions warranted initial follow-up. Follow-up analyses revealed 4 regions of continued interest on chromosomes 4, 6, 12, and 20, with the strongest results observed forchromosome 12. Peak 2-point affecteds-only lod scores (n=54) were 1.3, 1.6, 2.7, and 2.2 and affected relative pairs P values (n=54) were .04, .03, .14, and .04 for D12S373, D12S1057, D12S1042, and D12S390, respectively. Sibpair analysis (n=54) resulted in maximum lod scores (MLSs) of 1.5, 2.6, 3.2, and 2.3 for these markers, with a peak multipoint MLS of 3.5. A priori stratification by APOE genotype identified 27 families that had at least 1 member with AD whose genotype did not contain an APOE*4 allele. Analysis of these 27 families resulted in MLSs of 1.0, 2.4, 3.7, and 3.3 and a peak multipoint MLS of 3.9. A complete genomic screen in families affected with late-onset AD identified 4 regions of interest after follow-up. Chromosome 12 gave the strongest and most consistent results with a peak multipoint MLS of 3.5, suggesting that this region contains a new susceptibility gene for AD. Additional analyses are necessary to identify the chromosome 12 susceptibility gene for AD and to follow up the regions of interest on chromosomes 4, 6, and 20.

Pest resistance and agronomic performance of Upland cotton lines following eight generations of introgression of the BNL3279_105 DNA marker from Gossypium barbadense GB713

USDA-ARS?s Scientific Manuscript database

The BNL3279 primers give unique DNA markers that are closely linked with resistance to reniform nematodes in Gossypium longicalx, Gossypium barbadense GB713, and Gossypium aridum. Plants that had been selected and advanced based on reniform nematode bioassays for each of five or six generations of ...

Choline-stabilized orthosilicic acid supplementation as an adjunct to Calcium/Vitamin D3 stimulates markers of bone formation in osteopenic females: a randomized, placebo-controlled trial

PubMed Central

Spector, Tim D; Calomme, Mario R; Anderson, Simon H; Clement, Gail; Bevan, Liisa; Demeester, Nathalie; Swaminathan, Rami; Jugdaohsingh, Ravin; Berghe, Dirk A Vanden; Powell, Jonathan J

2008-01-01

Background Mounting evidence supports a physiological role for silicon (Si) as orthosilicic acid (OSA, Si(OH)4) in bone formation. The effect of oral choline-stabilized orthosilicic acid (ch-OSA) on markers of bone turnover and bone mineral density (BMD) was investigated in a double-blind placebo-controlled trial. Methods Over 12-months, 136 women out of 184 randomized (T-score spine < -1.5) completed the study and received, daily, 1000 mg Ca and 20 μg cholecalciferol (Vit D3) and three different ch-OSA doses (3, 6 and 12 mg Si) or placebo. Bone formation markers in serum and urinary resorption markers were measured at baseline, and after 6 and 12 months. Femoral and lumbar BMD were measured at baseline and after 12 months by DEXA. Results Overall, there was a trend for ch-OSA to confer some additional benefit to Ca and Vit D3 treatment, especially for markers of bone formation, but only the marker for type I collagen formation (PINP) was significant at 12 months for the 6 and 12 mg Si dose (vs. placebo) without a clear dose response effect. A trend for a dose-corresponding increase was observed in the bone resorption marker, collagen type I C-terminal telopeptide (CTX-I). Lumbar spine BMD did not change significantly. Post-hoc subgroup analysis (baseline T-score femur < -1) however was significant for the 6 mg dose at the femoral neck (T-test). There were no ch-OSA related adverse events observed and biochemical safety parameters remained within the normal range. Conclusion Combined therapy of ch-OSA and Ca/Vit D3 had a potential beneficial effect on bone collagen compared to Ca/Vit D3 alone which suggests that this treatment is of potential use in osteoporosis. NTR 1029 PMID:18547426

A cross-sectional study to evaluate the association of hyperbilirubinaemia on markers of cardiovascular disease, neurocognitive function, bone mineral density and renal markers in HIV-1 infected subjects on protease inhibitors.

PubMed

Barber, T J; Moyle, G; Hill, A; Jagjit Singh, G; Scourfield, A; Yapa, H M; Waters, L; Asboe, D; Boffito, M; Nelson, M

2016-05-01

Ongoing inflammation in controlled HIV infection contributes to non-AIDS comorbidities. High bilirubin appears to exhibit an anti-inflammatory effect in vivo. We therefore examined whether increased bilirubin in persons with HIV was associated with differences in markers of inflammation and cardiovascular, bone, renal disease, and neurocognitive (NC) impairment. This cross-sectional study examined inflammatory markers in individuals with stable HIV infection treated with two nucleoside reverse transcriptase inhibitors and a boosted protease inhibitor. Individuals recruited were those with a normal bilirubin (NBR; 0-17 μmol/L) or high bilirubin (>2.5 × upper limit of normal). Demographic and anthropological data were recorded. Blood and urine samples were taken for analyses. Pulse wave velocity (PWV) measurement, carotid intimal thickness (CIT), and calcaneal stiffness (CSI) were measured. Males were asked to answer a questionnaire about sexual function; NC testing was performed using CogState. 101 patients were screened, 78 enrolled (43 NBR and 35 HBR). Atazanavir use was significantly higher in HBR. Whilst a trend for lower CIT was seen in those with HBR, no significant differences were seen in PWV, bone markers, calculated cardiovascular risk (Framingham), or erectile dysfunction score. VCAM-1 levels were significantly lower in the HBR group. HBR was associated with lower LDL and triglyceride levels. NBR was associated with a calculated FRAX significantly lower than HBR although no associations were found after adjusting for tenofovir use. No difference in renal markers was observed. Component tests of NC testing revealed differences favouring HBR but overall composite scores were similar. High bilirubin in the context of boosted PI therapy was found not to be associated with differences in with the markers examined in this study. Some trends were noted and, on the basis of these, a larger, clinical end point study is warranted.

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

PubMed Central

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

2004-01-01

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

A Site-Specific Recombinase-Based Method to Produce Antibiotic Selectable Marker Free Transgenic Cattle

PubMed Central

Tong, Qi; Liu, Xu; Su, Feng; Quan, Fusheng; Guo, Zekun; Zhang, Yong

2013-01-01

Antibiotic selectable marker genes have been widely used to generate transgenic animals. Once transgenic animals have been obtained, the selectable marker is no longer necessary but raises public concerns regarding biological safety. The aim of this study was to prepare competent antibiotic selectable marker free transgenic cells for somatic cell nuclear transfer (SCNT). PhiC31 intergrase was used to insert a transgene cassette into a “safe harbor” in the bovine genome. Then, Cre recombinase was employed to excise the selectable marker under the monitoring of a fluorescent double reporter. By visually tracking the phenotypic switch from red to green fluorescence, antibiotic selectable marker free cells were easily detected and sorted by fluorescence-activated cell sorting. For safety, we used phiC31 mRNA and cell-permeant Cre protein in this study. When used as donor nuclei for SCNT, these safe harbor integrated marker-free transgenic cells supported a similar developmental competence of SCNT embryos compared with that of non-transgenic cells. After embryo transfer, antibiotic selectable marker free transgenic cattle were generated and anti-bacterial recombinant human β-defensin-3 in milk was detected during their lactation period. Thus, this approach offers a rapid and safe alternative to produce antibiotic selectable marker free transgenic farm animals, thereby making it a valuable tool to promote the healthy development and welfare of transgenic farm animals. PMID:23658729

Immunohistochemical differentiation of high-grade prostate carcinoma from urothelial carcinoma.

PubMed

Chuang, Ai-Ying; DeMarzo, Angelo M; Veltri, Robert W; Sharma, Rajni B; Bieberich, Charles J; Epstein, Jonathan I

2007-08-01

The histologic distinction between high-grade prostate cancer and infiltrating high-grade urothelial cancer may be difficult, and has significant implications because each disease may be treated very differently (ie, hormone therapy for prostate cancer and chemotherapy for urothelial cancer). Immunohistochemistry of novel and established prostatic and urothelial markers using tissue microarrays (TMAs) were studied. Prostatic markers studied included: prostate-specific antigen (PSA), prostein (P501s), prostate-specific membrane antigen (PSMA), NKX3.1 (an androgen-related tumor suppressor gene), and proPSA (pPSA) (precursor form of PSA). "Urothelial markers" included high molecular weight cytokeratin (HMWCK), p63, thrombomodulin, and S100P (placental S100). TMAs contained 38 poorly differentiated prostate cancers [Gleason score 8 (n=2), Gleason score 9 (n=18), Gleason score 10 (n=18)] and 35 high-grade invasive urothelial carcinomas from radical prostatectomy and cystectomy specimens, respectively. Each case had 2 to 8 tissue spots (0.6-mm diameter). If all spots for a case showed negative staining, the case was called negative. The sensitivities for labeling prostate cancers were PSA (97.4%), P501S (100%), PSMA (92.1%), NKX3.1 (94.7%), and pPSA (94.7%). Because of PSA's high sensitivity on the TMA, we chose 41 additional poorly differentiated primary (N=36) and metastatic (N=5) prostate carcinomas which showed variable PSA staining at the time of diagnosis and performed immunohistochemistry on routine tissue sections. Compared to PSA, which on average showed 18.8% of cells with moderate to strong positivity, cases stained for P501S, PSMA, and NKX3.1 had on average 42.5%, 53.7%, 52.9% immunoreactivity, respectively. All prostatic markers showed excellent specificity. HMWCK, p63, thrombomodulin, and S100P showed lower sensitivities in labeling high-grade invasive urothelial cancer in the TMAs with 91.4%, 82.9%, 68.6%, and 71.4% staining, respectively. These urothelial markers were relatively specific with only a few prostate cancers showing scattered (

Use of molecular genetic markers in forest management

Treesearch

Craig S. Echt

1997-01-01

When managing forests for biodiversity or sustainability, attention must be given to how silvicultural practices affect genetic diversity. A new generation of DNA-based markers affords a greater detail of genetic analysis than previously possible. These new markers, SSRs or microsatellites, have been used to demonstrate genetic diversity and infer evolutionary history...

IDENTIFICATION OF SEX CHROMOSOME MOLECULAR MARKERS USING RAPDS AND FLUORESCENT IN SITU HYBRIDIZATION IN RAINBOW TROUT

EPA Science Inventory

The goal of this work is to identify molecular markers associated with the sex chromosomes in rainbow trout to study the mode of sex determination mechanisms in this species. Using the RAPD assay and bulked segregant analysis, two markers were identified that generated polymorphi...

Application of next-generation sequencing for rapid marker development in molecular plant breeding: a case study on anthracnose disease resistance in Lupinus angustifolius L.

PubMed Central

2012-01-01

Background In the last 30 years, a number of DNA fingerprinting methods such as RFLP, RAPD, AFLP, SSR, DArT, have been extensively used in marker development for molecular plant breeding. However, it remains a daunting task to identify highly polymorphic and closely linked molecular markers for a target trait for molecular marker-assisted selection. The next-generation sequencing (NGS) technology is far more powerful than any existing generic DNA fingerprinting methods in generating DNA markers. In this study, we employed a grain legume crop Lupinus angustifolius (lupin) as a test case, and examined the utility of an NGS-based method of RAD (restriction-site associated DNA) sequencing as DNA fingerprinting for rapid, cost-effective marker development tagging a disease resistance gene for molecular breeding. Results Twenty informative plants from a cross of RxS (disease resistant x susceptible) in lupin were subjected to RAD single-end sequencing by multiplex identifiers. The entire RAD sequencing products were resolved in two lanes of the 16-lanes per run sequencing platform Solexa HiSeq2000. A total of 185 million raw reads, approximately 17 Gb of sequencing data, were collected. Sequence comparison among the 20 test plants discovered 8207 SNP markers. Filtration of DNA sequencing data with marker identification parameters resulted in the discovery of 38 molecular markers linked to the disease resistance gene Lanr1. Five randomly selected markers were converted into cost-effective, simple PCR-based markers. Linkage analysis using marker genotyping data and disease resistance phenotyping data on a F8 population consisting of 186 individual plants confirmed that all these five markers were linked to the R gene. Two of these newly developed sequence-specific PCR markers, AnSeq3 and AnSeq4, flanked the target R gene at a genetic distance of 0.9 centiMorgan (cM), and are now replacing the markers previously developed by a traditional DNA fingerprinting method for marker-assisted selection in the Australian national lupin breeding program. Conclusions We demonstrated that more than 30 molecular markers linked to a target gene of agronomic trait of interest can be identified from a small portion (1/8) of one sequencing run on HiSeq2000 by applying NGS based RAD sequencing in marker development. The markers developed by the strategy described in this study are all co-dominant SNP markers, which can readily be converted into high throughput multiplex format or low-cost, simple PCR-based markers desirable for large scale marker implementation in plant breeding programs. The high density and closely linked molecular markers associated with a target trait help to overcome a major bottleneck for implementation of molecular markers on a wide range of germplasm in breeding programs. We conclude that application of NGS based RAD sequencing as DNA fingerprinting is a very rapid and cost-effective strategy for marker development in molecular plant breeding. The strategy does not require any prior genome knowledge or molecular information for the species under investigation, and it is applicable to other plant species. PMID:22805587

Application of next-generation sequencing for rapid marker development in molecular plant breeding: a case study on anthracnose disease resistance in Lupinus angustifolius L.

PubMed

Yang, Huaan; Tao, Ye; Zheng, Zequn; Li, Chengdao; Sweetingham, Mark W; Howieson, John G

2012-07-17

In the last 30 years, a number of DNA fingerprinting methods such as RFLP, RAPD, AFLP, SSR, DArT, have been extensively used in marker development for molecular plant breeding. However, it remains a daunting task to identify highly polymorphic and closely linked molecular markers for a target trait for molecular marker-assisted selection. The next-generation sequencing (NGS) technology is far more powerful than any existing generic DNA fingerprinting methods in generating DNA markers. In this study, we employed a grain legume crop Lupinus angustifolius (lupin) as a test case, and examined the utility of an NGS-based method of RAD (restriction-site associated DNA) sequencing as DNA fingerprinting for rapid, cost-effective marker development tagging a disease resistance gene for molecular breeding. Twenty informative plants from a cross of RxS (disease resistant x susceptible) in lupin were subjected to RAD single-end sequencing by multiplex identifiers. The entire RAD sequencing products were resolved in two lanes of the 16-lanes per run sequencing platform Solexa HiSeq2000. A total of 185 million raw reads, approximately 17 Gb of sequencing data, were collected. Sequence comparison among the 20 test plants discovered 8207 SNP markers. Filtration of DNA sequencing data with marker identification parameters resulted in the discovery of 38 molecular markers linked to the disease resistance gene Lanr1. Five randomly selected markers were converted into cost-effective, simple PCR-based markers. Linkage analysis using marker genotyping data and disease resistance phenotyping data on a F8 population consisting of 186 individual plants confirmed that all these five markers were linked to the R gene. Two of these newly developed sequence-specific PCR markers, AnSeq3 and AnSeq4, flanked the target R gene at a genetic distance of 0.9 centiMorgan (cM), and are now replacing the markers previously developed by a traditional DNA fingerprinting method for marker-assisted selection in the Australian national lupin breeding program. We demonstrated that more than 30 molecular markers linked to a target gene of agronomic trait of interest can be identified from a small portion (1/8) of one sequencing run on HiSeq2000 by applying NGS based RAD sequencing in marker development. The markers developed by the strategy described in this study are all co-dominant SNP markers, which can readily be converted into high throughput multiplex format or low-cost, simple PCR-based markers desirable for large scale marker implementation in plant breeding programs. The high density and closely linked molecular markers associated with a target trait help to overcome a major bottleneck for implementation of molecular markers on a wide range of germplasm in breeding programs. We conclude that application of NGS based RAD sequencing as DNA fingerprinting is a very rapid and cost-effective strategy for marker development in molecular plant breeding. The strategy does not require any prior genome knowledge or molecular information for the species under investigation, and it is applicable to other plant species.

Differentiating constitutional thinness from anorexia nervosa in DSM 5 era.

PubMed

Estour, Bruno; Marouani, Nesrine; Sigaud, Torrance; Lang, François; Fakra, Eric; Ling, Yiin; Diamondé, Aurélie; Minnion, James S; Galusca, Bogdan; Germain, Natacha

2017-10-01

Constitutional thinness (CT) is an underweight state characterized by normal menstruations and no change in feeding behaviour. Thinness is the only resemblance between Anorexia Nervosa (AN) and CT. Removal of amenorrhea from the new DSM 5 definition of AN might result in misdiagnosis between these two populations. The objective of this study was to compare CT, AN and Control subjects in terms of biological, anthropometric, and psychological markers in order to better distinguish AN from CT subjects. Body composition, nutritional markers, pituitary hormones, bone markers and psychological scores were evaluated in three groups of young women: fifty-six CT, forty restrictive-type AN and fifty-four Control subjects. For every marker, a receiver Operator Characteristics (ROC) curve was calculated to evaluate the accuracy of differentiation between AN and CT groups. For most studied parameters, CT subjects were similar to Controls but dramatically different from AN subjects. DEBQ Restrained Eating subscale score was identified by ROC data analysis as the only psychological parameter tested to successfully differentiate AN from CT. Free-T3 and Leptin were shown to be powerful markers to differentiate AN and CT populations as they were highly specific and sensitive ones. The exclusive use of psychological testing criteria is not always sufficient to differentiate AN and CT patients. Minimally, additional testing of Free T3 levels, which is cheap and widely accessible for general practitioners, should be completed to avoid misdiagnosis which could result in the implementation of ineffective treatment plans and social stigmatization for CT women. Copyright © 2017 Elsevier Ltd. All rights reserved.

Integrated CLL Scoring System, a New and Simple Index to Predict Time to Treatment and Overall Survival in Patients With Chronic Lymphocytic Leukemia.

PubMed

Visentin, Andrea; Facco, Monica; Frezzato, Federica; Castelli, Monica; Trimarco, Valentina; Martini, Veronica; Gattazzo, Cristina; Severin, Filippo; Chiodin, Giorgia; Martines, Annalisa; Bonaldi, Laura; Gianesello, Ilaria; Pagnin, Elisa; Boscaro, Elisa; Piazza, Francesco; Zambello, Renato; Semenzato, Gianpietro; Trentin, Livio

2015-10-01

Several prognostic factors have been identified to predict the outcome of patients with chronic lymphocytic leukemia (CLL), but only a few studies analyzed more markers together. Taking advantage of a population of 608 patients, we identified the strongest prognostic markers of survival and, subsequently, in a cohort of 212 patients we integrated data of cytogenetic lesions, IGHV mutational status, and CD38 expression in a new and easy scoring system we called the integrated CLL scoring system (ICSS). ICSS defines 3 groups of risk: (1) low risk (patients with 13q(-) or normal fluorescence in-situ hybridization analysis results, mutated IGHV, and CD38) (2) high risk (all 11q(-) or 17p(-) patients and/or all unmutated IGHV and CD38(+) patients); and (3) intermediate risk (all remaining patients). Using only these 3 already available prognostic factors, we were able to properly redefine patients and better predict the clinical course of the disease. ICSS could become a useful tool for CLL patients' management. Copyright © 2015 Elsevier Inc. All rights reserved.

The effect of a period of intense exercise on the marker approach to detect growth hormone doping in sports.

PubMed

Voss, Sven Christian; Robinson, Neil; Alsayrafi, Mohammed; Bourdon, Pitre C; Schumacher, Yorck Olaf; Saugy, Martial; Giraud, Sylvain

2014-06-01

The major objective of this study was to investigate the effects of several days of intense exercise on the growth hormone marker approach to detect doping with human growth hormone (hGH). In addition we investigated the effect of changes in plasma volume on the test. Fifteen male athletes performed a simulated nine-day cycling stage race. Blood samples were collected twice daily over a period of 15 days (stage race + three days before and after). Plasma volumes were estimated by the optimized CO Rebreathing method. IGF-1 and P-III-NP were analyzed by Siemens Immulite and Cisbio Assays, respectively. All measured GH 2000 scores were far below the published decision limits for an adverse analytical finding. The period of exercise did not increase the GH-scores; however the accompanying effect of the increase in Plasma Volume yielded in essentially lower GH-scores. We could demonstrate that a period of heavy, long-term exercise with changes in plasma volume does not interfere with the decision limits for an adverse analytical finding. Copyright © 2014 John Wiley & Sons, Ltd.

The Dynamics of Self-Esteem in Cognitive Therapy for Avoidant and Obsessive-Compulsive Personality Disorders: An Adaptive Role of Self-Esteem Variability?

PubMed Central

Cummings, Jorden A.; Hayes, Adele M.; Cardaciotto, LeeAnn; Newman, Cory F.

2011-01-01

Self-esteem variability is often associated with poor functioning. However, in disorders with entrenched negative views of self and in a context designed to challenge those views, variable self-esteem might represent a marker of change. We examined self-esteem variability in a sample of 27 patients with Avoidant and Obsessive-Compulsive Personality Disorders who received Cognitive Therapy (CT). A therapy coding system was used to rate patients’ positive and negative views of self expressed in the first ten sessions of a 52-week treatment. Ratings of negative (reverse scored) and positive view of self were summed to create a composite score for each session. Self-esteem variability was calculated as the standard deviation of self-esteem scores across sessions. More self-esteem variability predicted more improvement in personality disorder and depression symptoms at the end of treatment, beyond baseline and average self-esteem. Early variability in self-esteem, in this population and context, appeared to be a marker of therapeutic change. PMID:22923855

A Genetic Response Score for Hydrochlorothiazide Use: Insights From Genomics and Metabolomics Integration.

PubMed

Shahin, Mohamed H; Gong, Yan; McDonough, Caitrin W; Rotroff, Daniel M; Beitelshees, Amber L; Garrett, Timothy J; Gums, John G; Motsinger-Reif, Alison; Chapman, Arlene B; Turner, Stephen T; Boerwinkle, Eric; Frye, Reginald F; Fiehn, Oliver; Cooper-DeHoff, Rhonda M; Kaddurah-Daouk, Rima; Johnson, Julie A

2016-09-01

Hydrochlorothiazide is among the most commonly prescribed antihypertensives; yet, <50% of hydrochlorothiazide-treated patients achieve blood pressure (BP) control. Herein, we integrated metabolomic and genomic profiles of hydrochlorothiazide-treated patients to identify novel genetic markers associated with hydrochlorothiazide BP response. The primary analysis included 228 white hypertensives treated with hydrochlorothiazide from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study. Genome-wide analysis was conducted using Illumina Omni 1 mol/L-Quad Chip, and untargeted metabolomics was performed on baseline fasting plasma samples using a gas chromatography-time-of-flight mass spectrometry platform. We found 13 metabolites significantly associated with hydrochlorothiazide systolic BP (SBP) and diastolic BP (DBP) responses (false discovery rate, <0.05). In addition, integrating genomic and metabolomic data revealed 3 polymorphisms (rs2727563 PRKAG2, rs12604940 DCC, and rs13262930 EPHX2) along with arachidonic acid, converging in the netrin signaling pathway (P=1×10(-5)), as potential markers, significantly influencing hydrochlorothiazide BP response. We successfully replicated the 3 genetic signals in 212 white hypertensives treated with hydrochlorothiazide and created a response score by summing their BP-lowering alleles. We found patients carrying 1 response allele had a significantly lower response than carriers of 6 alleles (∆SBP/∆DBP: -1.5/1.2 versus -16.3/-10.4 mm Hg, respectively, SBP score, P=1×10(-8) and DBP score, P=3×10(-9)). This score explained 11.3% and 11.9% of the variability in hydrochlorothiazide SBP and DBP responses, respectively, and was further validated in another independent study of 196 whites treated with hydrochlorothiazide (DBP score, P=0.03; SBP score, P=0.07). This study suggests that PRKAG2, DCC, and EPHX2 might be important determinants of hydrochlorothiazide BP response. © 2016 American Heart Association, Inc.

A Practical Standardized Composite Nutrition Score Based on Lean Tissue Index: Application in Nutrition Screening and Prediction of Outcome in Hemodialysis Population.

PubMed

Chen, Huan-Sheng; Cheng, Chun-Ting; Hou, Chun-Cheng; Liou, Hung-Hsiang; Chang, Cheng-Tsung; Lin, Chun-Ju; Wu, Tsai-Kun; Chen, Chang-Hsu; Lim, Paik-Seong

2017-07-01

Rapid screening and monitoring of nutritional status is mandatory in hemodialysis population because of the increasingly encountered nutritional problems. Considering the limitations of previous composite nutrition scores applied in this population, we tried to develop a standardized composite nutrition score (SCNS) using low lean tissue index as a marker of protein wasting to facilitate clinical screening and monitoring and to predict outcome. This retrospective cohort used 2 databases of dialysis populations from Taiwan between 2011 and 2014. First database consisting of data from 629 maintenance hemodialysis patients was used to develop the SCNS and the second database containing data from 297 maintenance hemodialysis patients was used to validate this developed score. SCNS containing albumin, creatinine, potassium, and body mass index was developed from the first database using low lean tissue index as a marker of protein wasting. When applying this score in the original database, significantly higher risk of developing protein wasting was found for patients with lower SCNS (odds ratio 1.38 [middle tertile vs highest tertile, P < .0001] and 2.40 [lowest tertile vs middle tertile, P < .0001]). The risk of death was also shown to be higher for patients with lower SCNS (hazard ratio 4.45 [below median level vs above median level, P < .0001]). These results were validated in the second database. We developed an SCNS consisting of 4 easily available biochemical parameters. This kind of scoring system can be easily applied in different dialysis facilities for screening and monitoring of protein wasting. The wide application of body composition monitor in dialysis population will also facilitate the development of specific nutrition scoring model for individual facility. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Perthes Disease: The Quality and Reliability of Information on the Internet.

PubMed

Nassiri, Mujtaba; Bruce-Brand, Robert A; O'Neill, Francis; Chenouri, Shojaeddin; Curtin, Paul

2015-01-01

Research has shown that up to 89% of parents used the Internet to seek health information regarding their child's medical condition. Much of the information on the Internet is valuable; however, the quality of health information is variable and unregulated. The aim of this study was to evaluate the quality and content of information about Perthes disease on the Internet using recognized scoring systems, identification of quality markers, and describe a novel specific score. We searched the top 3 search engines (Google, Yahoo!, and Bing) for the following keywords: "Perthes disease." Forty-five unique Web sites were identified. The Web sites were then categorized by type and assessed using the DISCERN score, the Journal of the American Medical Association (JAMA) benchmark criteria, and a novel Perthes-specific Content score. The presence of the Health On the Net (HON) code, a reported quality assurance marker, was noted. Of the Web sites analyzed, the Majority were Governmental and Nonprofit Organizations (NPO) (37.8%), followed by commercial Web sites (22.2%). Only 6 of the Web sites were HONcode certified. The mean DISCERN score was 53.1 (SD=9.0). The Governmental and NPO Web sites had the highest overall DISCERN scores followed closely by Physician Web sites. The mean JAMA benchmark criteria score was 2.1 (SD=1.2). Nine Web sites had maximal scores and the Academic Web sites had the highest overall JAMA benchmark scores. DISCERN scores, JAMA benchmark scores, and Perthes-specific Content scores were all greater for Web sites that bore the HONcode seal. The quality of information available online regarding Perthes disease is of variable quality. Governmental and NPO Web sites predominate and also provide higher quality content. The HONcode seal is a reliable indicator of Web site quality. Physicians should recommend the HONcode seal to their patients as a reliable indicator of Web site quality or, better yet, refer patients to sites they have personally reviewed. Supplying parents with a guide to health information on the Internet will help exclude Web sites as sources of misinformation.

A Diagnostic Marker to Discriminate Childhood Apraxia of Speech From Speech Delay: III. Theoretical Coherence of the Pause Marker with Speech Processing Deficits in Childhood Apraxia of Speech

PubMed Central

Strand, Edythe A.; Fourakis, Marios; Jakielski, Kathy J.; Hall, Sheryl D.; Karlsson, Heather B.; Mabie, Heather L.; McSweeny, Jane L.; Tilkens, Christie M.; Wilson, David L.

2017-01-01

Purpose Previous articles in this supplement described rationale for and development of the pause marker (PM), a diagnostic marker of childhood apraxia of speech (CAS), and studies supporting its validity and reliability. The present article assesses the theoretical coherence of the PM with speech processing deficits in CAS. Method PM and other scores were obtained for 264 participants in 6 groups: CAS in idiopathic, neurogenetic, and complex neurodevelopmental disorders; adult-onset apraxia of speech (AAS) consequent to stroke and primary progressive apraxia of speech; and idiopathic speech delay. Results Participants with CAS and AAS had significantly lower scores than typically speaking reference participants and speech delay controls on measures posited to assess representational and transcoding processes. Representational deficits differed between CAS and AAS groups, with support for both underspecified linguistic representations and memory/access deficits in CAS, but for only the latter in AAS. CAS–AAS similarities in the age–sex standardized percentages of occurrence of the most frequent type of inappropriate pauses (abrupt) and significant differences in the standardized occurrence of appropriate pauses were consistent with speech processing findings. Conclusions Results support the hypotheses of core representational and transcoding speech processing deficits in CAS and theoretical coherence of the PM's pause-speech elements with these deficits. PMID:28384751

Copeptin Levels Remain Unchanged during the Menstrual Cycle

PubMed Central

Blum, Claudine A.; Mirza, Uzma; Christ-Crain, Mirjam; Mueller, Beat; Schindler, Christian; Puder, Jardena J.

2014-01-01

Background Copeptin, a surrogate marker for arginin vasopressin production, is evaluated as an osmo-dependent stress and inflammatory biomarker in different diseases. We investigated copeptin during the menstrual cycle and its relationship to sex hormones, markers of subclinical inflammation and estimates of body fluid. Methods In 15 healthy women with regular menstrual cycles, blood was drawn on fifteen defined days of their menstrual cycle and was assayed for copeptin, progesterone, estradiol, luteinizing hormone, high-sensitive C-reactive protein, tumor necrosis factor-alpha and procalcitonin. Symptoms of fluid retention were assessed on each visit, and bio impedance analysis was measured thrice to estimate body fluid changes. Mixed linear model analysis was performed to assess the changes of copeptin across the menstrual cycle and the relationship of sex hormones, markers of subclinical inflammation and estimates of body fluid with copeptin. Results Copeptin levels did not significantly change during the menstrual cycle (p = 0.16). Throughout the menstrual cycle, changes in estradiol (p = 0.002) and in the physical premenstrual symptom score (p = 0.01) were positively related to copeptin, but changes in other sex hormones, in markers of subclinical inflammation or in bio impedance analysis-estimated body fluid were not (all p = ns). Conclusion Although changes in estradiol and the physical premenstrual symptom score appear to be related to copeptin changes, copeptin does not significantly change during the menstrual cycle. PMID:24866705

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.

Inflammatory and nutritional statuses of patients submitted to resection of gastrointestinal tumors.

PubMed

Fruchtenicht, Ana Valéria Gonçalves; Poziomyck, Aline Kirjner; Reis, Audrey Machado Dos; Galia, Carlos Roberto; Kabke, Georgia Brum; Moreira, Luis Fernando

2018-01-01

to evaluate the association between the nutritional and the inflammatory statuses of patients with cancer of the gastrointestinal tract undergoing surgical resection and to identify predictors of mortality in these patients. we conducted a prospective study of 41 patients with gastrointestinal tract cancer submitted to surgery between October 2012 and December 2014. We evaluated the nutritional status by subjective and objective methods. We assessed the inflammatory response and prognosis using the modified Glasgow Prognostic Score (mGPS), Neutrophil/Lymphocyte Ratio (NLR), Onodera Prognostic Nutritional Index (mPNI), Inflammatory-Nutritional Index (INI) and C-Reactive Protein/Albumin ratio (mPINI). half of the patients were malnourished and 27% were at nutritional risk. There was a positive association between the percentage of weight loss (%WL) and the markers NLR (p=0.047), mPINI (p=0.014) and INI (p=0.015). Serum albumin levels (p=0.015), INI (p=0.026) and mPINI (p=0.026) were significantly associated with the PG-SGA categories. On multivariate analysis, albumin was the only inflammatory marker independently related to death (p=0.004). inflammatory markers were significantly associated with malnutrition, demonstrating that the higher the inflammatory response, the worse the PG-SGA (B and C) scores and the higher the %WL in these patients. However, further studies aimed at improving surgical outcomes and determining the role of these markers as predictors of mortality are required.

Biological ageing and frailty markers in breast cancer patients.

PubMed

Brouwers, Barbara; Dalmasso, Bruna; Hatse, Sigrid; Laenen, Annouschka; Kenis, Cindy; Swerts, Evalien; Neven, Patrick; Smeets, Ann; Schöffski, Patrick; Wildiers, Hans

2015-05-01

Older cancer patients are a highly heterogeneous population in terms of global health and physiological reserves, and it is often difficult to determine the best treatment. Moreover, clinical tools currently used to assess global health require dedicated time and lack a standardized end score. Circulating markers of biological age and/or fitness could complement or partially substitute the existing screening tools. In this study we explored the relationship of potential ageing/frailty biomarkers with age and clinical frailty. On a population of 82 young and 162 older non-metastatic breast cancer patients, we measured mean leukocyte telomere length and plasma levels of interleukin-6 (IL-6), regulated upon activation, normal T cell expressed and secreted (RANTES), monocyte chemotactic protein 1 (MCP-1), insulin-like growth factor 1 (IGF-1). We also developed a new tool to summarize clinical frailty, designated Leuven Oncogeriatric Frailty Score (LOFS), by integrating GA results in a single, semi-continuous score. LOFS' median score was 8, on a scale from 0=frail to 10=fit. IL-6 levels were associated with chronological age in both groups and with clinical frailty in older breast cancer patients, whereas telomere length, IGF-1 and MCP-1 only correlated with age. Plasma IL-6 should be further explored as frailty biomarker in cancer patients.

[Cognitive markers to discriminate between mild cognitive impairment and normal ageing].

PubMed

Rodríguez Rodríguez, Nely; Juncos-Rabadán, Onésimo; Facal Mayo, David

2008-01-01

mild cognitive impairment (MCI) has been characterized as a transitional stage between normal ageing and dementia. The aim of the present study was to examine differences between normal ageing and MCI in the performance of several cognitive tests. These differences might serve as differential markers. we performed a longitudinal study (24 months) with two evaluations at 12-monthly intervals using the CAMCOG-R and a verbal learning test [test de aprendizaje verbal España-Complutense (TAVEC)]. The sample was composed of 25 persons aged more than 50 years old (five men and 20 women), distributed into two groups: the control group and the MCI group. To assign persons to either of the two groups, Petersen's MCI criteria were applied to Mini-Mental State Examination (MMSE) scores. repeated measures ANOVA (2 groups x 2 assessment) showed significant differences between the MCI and control group in the CAMCOG-R scores in orientation, language, memory, abstract thinking, executive function and global score and in the TAVEC scores for immediate recall and short- and long-term free and clued recall. No significant differences were found between the first and second assessment or in the interaction group assessment. the results of the present study confirm that the CAMCOG-R and the TAVEC effectively discriminate between normal ageing and MCI and can be used complementarily.

Rumination as a Marker of Psychological Improvement in Transsexual Women Postoperative

PubMed Central

Mueller, Andressa; Quadros, Cláudia; Schwarz, Karine; Brandelli Costa, Angelo; Vaitses Fontanari, Anna Martha; Machado Borba Soll, Bianca; Cardoso da Silva, Dhiordan; Abel Schneider, Maiko; de Moura Silveira, Érico; Kauer-Sant'Anna, Marcia; Rodrigues Lobato, Maria Inês

2016-01-01

Abstract Purpose: This study aimed to analyze rumination levels of transsexual women before and after gender affirmation surgery (GAS). Rumination scores may represent a broader measure of GAS success and an alternative to patient-reported satisfaction, quality of life, well-being, or the presence of “caseness” for anxiety or depression as previously established in the literature. Methods: Thirty-nine transsexual women were recruited. The participants completed the rumination scale of the Response Styles Questionnaire (RSQ) and were divided into three subsets according to the treatment time. Results: The rumination scores were lower in the transsexual women who had undergone surgical procedures on primary sexual characteristics and gradually decreased with each additional procedure completed with respect to secondary sexual characteristics. Conclusion: Rumination appears to comprise an important marker of improvement in post-GAS transsexual women. PMID:28861541

Linkage analysis of autopsy-confirmed familial Alzheimer disease supports an Alzheimer disease locus in 8q24.

PubMed

Sillén, Anna; Brohede, Jesper; Forsell, Charlotte; Lilius, Lena; Andrade, Jorge; Odeberg, Jacob; Kimura, Toru; Winblad, Bengt; Graff, Caroline

2011-01-01

We have previously reported the results of an extended genome-wide scan of Swedish Alzheimer disease (AD)-affected families; in this paper, we analyzed a subset of these families with autopsy-confirmed AD. We report the fine-mapping, using both microsatellite markers and single-nucleotide polymorphisms (SNPs), in the observed maximum logarithm of the odds (LOD)-2 unit (LOD(max)-2) region under the identified linkage peak, linkage analysis of the fine-mapping data with additionally analyzed pedigrees, and association analysis of SNPs selected from candidate genes in the linked interval. The subset was made on the criterion of at least one autopsy-confirmed AD case per family, resulting in 24 families. Linkage analysis of a family subset having at least one autopsy-confirmed AD case showed a significant nonparametric single-point LOD score of 4.4 in 8q24. Fine-mapping under the linkage peak with 10 microsatellite markers yielded an increase in the multipoint (mpt) LOD score from 2.1 to 3.0. SNP genotyping was performed on 21 selected candidate transcripts of the LOD(max)-2 region. Both family-based association and linkage analysis were performed on extended material from 30 families, resulting in a suggestive linkage at peak marker rs6577853 (mpt LOD score = 2.4). The 8q24 region has been implicated to be involved in AD etiology. Copyright © 2011 S. Karger AG, Basel.

Prognostic Value of Risk Score and Urinary Markers in Idiopathic Membranous Nephropathy

PubMed Central

Hofstra, Julia M.; Wetzels, Jack F.M.

2012-01-01

Summary Background and objectives Accurate prediction of prognosis may improve management of patients with idiopathic membranous nephropathy. This study compared the Toronto Risk Score and urinary low-molecular weight proteins. Design, setting, participants, & measurements One hundred four patients with biopsy-proven idiopathic membranous nephropathy who presented between 1995 and 2008 with a well-preserved kidney function and nephrotic range proteinuria were included. Urinary β2-microglobulin and α1-microglobulin measurements were obtained by timed standardized measurements, and the Toronto Risk Score was calculated using data obtained from medical records. The endpoint was progression, which was defined as an increase in serum creatinine>50% or >25% with a concentration>135 μmol/L. Results Forty-nine patients showed progression. The area under the receiver-operating characteristics curve was 0.78 (95% confidence interval=0.69–0.88) for the risk score versus 0.80 (0.71–0.89) and 0.79 (0.71–0.88) for urinary β2- and α1-microglobulin, respectively. Differences were not significant. Persistent proteinuria did not add accuracy to the Toronto Risk Score. Conversely, its accuracy was not reduced when data from the first 6 months of follow-up were used. Furthermore, a score based on GFR estimated with the six-variable Modification of Diet in Renal Disease equation, calculated in the first 6 months of follow-up, gave an area under the receiver-operating characteristics curve of 0.83 (0.74–0.92), which was not statistically different from other markers. Conclusions The prognostic accuracies of the Toronto Risk Score and urinary low-molecular weight proteins were not significantly different. The risk score can be calculated within 6 months of diagnosis, and a simplified risk score using estimated GFR–Modification of Diet in Renal Disease may be sufficient. PMID:22595828

The Somatic Marker Hypothesis and Sexual Decision Making: Understanding the Role of Iowa Gambling Task Performance and Daily Sexual Arousal on the Sexual Behavior of Gay and Bisexual Men.

PubMed

Rendina, H Jonathon; Millar, Brett M; Dash, Genevieve; Feldstein Ewing, Sarah W; Parsons, Jeffrey T

2018-04-19

The sexual decision-making literature suggests that sexual arousal and behavior are associated. The somatic marker hypothesis suggests that individual neuropsychological differences in decision making, as measured by the Iowa Gambling Task (IGT), may moderate these associations; however, this hypothesis has yet to be tested with event-level sexual behavior data. We hypothesized that (a) daily sexual arousal would be positively associated with likelihood of engaging in sex and condomless anal sex (CAS) and (b) IGT scores would moderate these associations such that the associations would be stronger among those with higher IGT scores. We used daily diary data from 334 highly sexually active gay and bisexual men to examine the main and interaction effects of sexual arousal and IGT scores on sexual engagement and CAS. As hypothesized, daily sexual arousal was positively associated with greater odds of both sexual engagement and CAS with casual male partners. Individual-level IGT performance significantly moderated the day-level association between arousal and sexual engagement, which was stronger for men with higher IGT scores. There was no main effect of IGT scores on either sexual behavior outcome, nor did it moderate the association between arousal and CAS. These findings highlight the influence of sexual arousal on sexual engagement, which differed by IGT scores; the effect of arousal on CAS was much less variable and may not be moderated by neurocognitive factors. This study supports the importance of exploring integrated behavioral/biomedical interventions to improve individual decision making to prevent HIV infection.

Concurrent change in dehydroepiandrosterone sulfate and functional performance in the oldest old: results from the Cardiovascular Health Study All Stars study.

PubMed

Sanders, J L; Cappola, A R; Arnold, A M; Boudreau, R M; Chaves, P H; Robbins, J; Cushman, M; Newman, A B

2010-09-01

The correlation between dehydroepiandrosterone sulfate (DHEAS) decline and age led to the hypothesis that DHEAS might be a marker of primary aging, though conflicting data from observational studies of mortality do not support this. We evaluated concurrent DHEAS and functional decline in a very old cohort to test if DHEAS change tracks with functional change during aging. DHEAS and functional performance (gait speed, grip strength, Modified Mini-Mental State Examination [3MSE] score, and digit symbol substitution test [DSST] score) were measured in 1996-1997 and 2005-2006 in 989 participants in the Cardiovascular Health Study All Stars study (mean age 85.2 years in 2005-2006, 63.5% women and 16.5% African American). We used multivariable linear regression to test the association of DHEAS decline with functional decline. After adjustment, each standard deviation decrease in DHEAS was associated with greater declines in gait speed (0.12 m/s, p = .01), grip strength (0.09 kg, p = .03), 3MSE score (0.13 points, p < .001), and DSST score (0.14 points, p = .001) in women only. Additional adjustment for baseline DHEAS attenuated the association with grip strength but did not alter other estimates appreciably, and baseline DHEAS was unassociated with functional decline. In this cohort of very old individuals, DHEAS decline tracked with declines in gait speed, 3MSE score, and DSST score, but not grip strength, in women independent of baseline DHEAS level. DHEAS decline might be a marker for age-associated performance decline, but its relevance is specific to women.

Back to the future: the Mediterranean diet paradigm.

PubMed

Naska, A; Trichopoulou, A

2014-03-01

The Mediterranean diet was introduced to the scientific community by the classic Seven Countries study. Since then data on the association between this diet and cardiovascular disease, cancer and other chronic diseases have been accumulating. The Mediterranean diet is characterized by a high intake of olive oil, plant products, fish and seafood; a low intake of dairies, meat and meat products; and a moderate ethanol intake. The Mediterranean diet has been operationalized through various computational scores (e.g. the Mediterranean diet score for adults and the KIDMED index for children) which are all based on the dietary components that capture its essence. Next to evidence generated through both observational studies and intervention trials on the inverse association between Mediterranean diet and several risk factors, inflammatory markers and mortality or incidence of disease, there is increasing evidence that Mediterranean populations are abandoning their traditional eating habits. Publications presenting changes over time in the diet of populations participating in the Seven Countries Study point towards an increase in the intake of processed foods and saturated fat and a decrease in the intake of plant foods and monounsaturated fatty acids. Findings are alarming, particularly in relation to younger generations. Studies among children and adolescents in the Mediterranean region clearly indicate that the largest proportions of these populations poorly adhere to their traditional diet. Mediterraneans have clearly not been the major benefactors in the research on the effects of the Mediterranean lifestyle and younger populations in the regions are already following the wrong path. Copyright © 2013 Elsevier B.V. All rights reserved.

Learning implicit brain MRI manifolds with deep learning

NASA Astrophysics Data System (ADS)

Bermudez, Camilo; Plassard, Andrew J.; Davis, Larry T.; Newton, Allen T.; Resnick, Susan M.; Landman, Bennett A.

2018-03-01

An important task in image processing and neuroimaging is to extract quantitative information from the acquired images in order to make observations about the presence of disease or markers of development in populations. Having a low-dimensional manifold of an image allows for easier statistical comparisons between groups and the synthesis of group representatives. Previous studies have sought to identify the best mapping of brain MRI to a low-dimensional manifold, but have been limited by assumptions of explicit similarity measures. In this work, we use deep learning techniques to investigate implicit manifolds of normal brains and generate new, high-quality images. We explore implicit manifolds by addressing the problems of image synthesis and image denoising as important tools in manifold learning. First, we propose the unsupervised synthesis of T1-weighted brain MRI using a Generative Adversarial Network (GAN) by learning from 528 examples of 2D axial slices of brain MRI. Synthesized images were first shown to be unique by performing a cross-correlation with the training set. Real and synthesized images were then assessed in a blinded manner by two imaging experts providing an image quality score of 1-5. The quality score of the synthetic image showed substantial overlap with that of the real images. Moreover, we use an autoencoder with skip connections for image denoising, showing that the proposed method results in higher PSNR than FSL SUSAN after denoising. This work shows the power of artificial networks to synthesize realistic imaging data, which can be used to improve image processing techniques and provide a quantitative framework to structural changes in the brain.

PPM-X: a new X-linked mental retardation syndrome with psychosis, pyramidal signs, and macroorchidism maps to Xq28.

PubMed Central

Lindsay, S.; Splitt, M.; Edney, S.; Berney, T. P.; Knight, S. J.; Davies, K. E.; O'Brien, O.; Gale, M.; Burn, J.

1996-01-01

We report a three-generation family manifesting a previously undescribed X-linked mental retardation syndrome. Four of the six moderately retarded males have had episodes of manic-depressive psychosis. The phenotype also includes pyramidal signs, Parkinsonian features, and macroorchidism, but there are no characteristic dysmorphic facial features. Affected males do not show fragile sites at distal Xq on cytogenetic analysis, nor do they have expansions of the CGG repeats at the FRAXA, FRAXE, or FRAXF loci. Linkage analyses were undertaken, and a maximal LOD score of 3.311 at theta = .0 was observed with the microsatellite marker DXS1123 in Xq28. A recombination was detected in one of the affected males with DXS1691 (Xq28), which gives the proximal boundary of the localization. No distal recombination has been detected at any of the loci tested. Images Figure 2 PMID:8651288

Prevalence and Distribution of Coronary Artery Calcification in Asymptomatic United States and Korean Adults　- Cross-Sectional Propensity-Matched Analysis.

PubMed

Han, Donghee; Ó Hartaigh, Bríain; Gransar, Heidi; Lee, Ji Hyun; Choi, Su-Yeon; Chun, Eun Ju; Sung, Jidong; Han, Hae-Won; Park, Sung Hak; Callister, Tracy; Lin, Fay Y; Min, James K; Chang, Hyuk-Jae

2016-10-25

The incidence of coronary artery disease (CAD) varies depending on ethnicity, but the precise differences remain to be firmly established. This study therefore evaluated the disparity in coronary artery calcification (CAC), as a marker of CAD, in asymptomatic US and Korean adults.Methods and Results:CAC score was compared between asymptomatic Korean (n=15,128) and US (n=7,533) adults. Propensity score matching was performed according to age, gender, hypertension, diabetes, dyslipidemia, and current smoking, which generated 2 cohorts of 5,427 matched pairs. Both cohorts were categorized according to age group: 45-54, 55-64, and 65-74 years. Overall, the prevalence of CAC score >0, >100, and >400 in Korean adults was lower than in US adults (P<0.001, all). According to increasing age groups, the likelihood of CAC was most often lower in Korean adults, especially in Korean women. The odds of having CAC >400 in Korean adults aged 65-74 years was 0.66 (95% CI: 0.48-0.91) overall, 0.78 (95% CI: 0.52-1.19) in men, and 0.50 (95% CI: 0.29-0.86) in women, compared with US counterparts. Korean adults have a lower prevalence and severity of atherosclerotic burden as assessed on CAC, compared with US adults, but the disparity in CAC according to ethnicity may decline with older age. (Circ J 2016; 80: 2349-2355).

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.

From genomics to functional markers in the era of next-generation sequencing.

PubMed

Salgotra, R K; Gupta, B B; Stewart, C N

2014-03-01

The availability of complete genome sequences, along with other genomic resources for Arabidopsis, rice, pigeon pea, soybean and other crops, has revolutionized our understanding of the genetic make-up of plants. Next-generation DNA sequencing (NGS) has facilitated single nucleotide polymorphism discovery in plants. Functionally-characterized sequences can be identified and functional markers (FMs) for important traits can be developed at an ever-increasing ease. FMs are derived from sequence polymorphisms found in allelic variants of a functional gene. Linkage disequilibrium-based association mapping and homologous recombinants have been developed for identification of "perfect" markers for their use in crop improvement practices. Compared with many other molecular markers, FMs derived from the functionally characterized sequence genes using NGS techniques and their use provide opportunities to develop high-yielding plant genotypes resistant to various stresses at a fast pace.

Association between markers of endothelial dysfunction and early signs of renal dysfunction in pediatric obesity and type 1 diabetes.

PubMed

Marcovecchio, M L; de Giorgis, T; Di Giovanni, I; Chiavaroli, V; Chiarelli, F; Mohn, A

2017-06-01

To evaluate whether circulating markers of endothelial dysfunction, such as intercellular adhesion molecule-1 (ICAM-1) and myeloperoxidase (MPO), are increased in youth with obesity and in those with type 1 diabetes (T1D) at similar levels, and whether their levels are associated with markers of renal function. A total of 60 obese youth [M/F: 30/30, age: 12.5 ± 2.8 yr; body mass index (BMI) z-score: 2.26 ± 0.46], 30 with T1D (M/F: 15/15; age: 12.9 ± 2.4 yr; BMI z-score: 0.45 ± 0.77), and 30 healthy controls (M/F: 15/15, age: 12.4 ± 3.3 yr, BMI z-score: -0.25 ± 0.56) were recruited. Anthropometric measurements were assessed and a blood sample was collected to measure ICAM-1, MPO, creatinine, cystatin C and lipid levels. A 24-h urine collection was obtained for assessing albumin excretion rate (AER). Levels of ICAM-1 and MPO were significantly higher in obese [ICAM-1: 0.606 (0.460-1.033) µg/mL; MPO: 136.6 (69.7-220.8) ng/mL] and T1D children [ICAM-1: 0.729 (0.507-0.990) µg/mL; MPO: 139.5 (51.0-321.3) ng/mL] compared with control children [ICAM-1: 0.395 (0.272-0.596) µg/mL MPO: 41.3 (39.7-106.9) ng/mL], whereas no significant difference was found between T1D and obese children. BMI z-score was significantly associated with ICAM-1 (β = 0.21, p = 0.02) and MPO (β = 0.41, p < 0.001). A statistically significant association was also found between ICAM-1 and markers of renal function (AER: β = 0.21, p = 0.03; e-GFR: β = 0.19, p = 0.04), after adjusting for BMI. Obese children have increased markers of endothelial dysfunction and early signs of renal damage, similarly to children with T1D, confirming obesity to be a cardiovascular risk factor as T1D. The association between ICAM-1 with e-GFR and AER confirm the known the association between general endothelial and renal dysfunction. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

DNA Repair Biomarkers Predict Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer

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

Alexander, Brian M., E-mail: bmalexander@lroc.harvard.edu; Wang Xiaozhe; Niemierko, Andrzej

2012-05-01

Purpose: The addition of neoadjuvant chemoradiotherapy prior to surgical resection for esophageal cancer has improved clinical outcomes in some trials. Pathologic complete response (pCR) following neoadjuvant therapy is associated with better clinical outcome in these patients, but only 22% to 40% of patients achieve pCR. Because both chemotherapy and radiotherapy act by inducing DNA damage, we analyzed proteins selected from multiple DNA repair pathways, using quantitative immunohistochemistry coupled with a digital pathology platform, as possible biomarkers of treatment response and clinical outcome. Methods and Materials: We identified 79 patients diagnosed with esophageal cancer between October 1994 and September 2002, withmore » biopsy tissue available, who underwent neoadjuvant chemoradiotherapy prior to surgery at the Massachusetts General Hospital and used their archived, formalin-fixed, paraffin-embedded biopsy samples to create tissue microarrays (TMA). TMA sections were stained using antibodies against proteins in various DNA repair pathways including XPF, FANCD2, PAR, MLH1, PARP1, and phosphorylated MAPKAP kinase 2 (pMK2). Stained TMA slides were evaluated using machine-based image analysis, and scoring incorporated both the intensity and the quantity of positive tumor nuclei. Biomarker scores and clinical data were assessed for correlations with clinical outcome. Results: Higher scores for MLH1 (p = 0.018) and lower scores for FANCD2 (p = 0.037) were associated with pathologic response to neoadjuvant chemoradiation on multivariable analysis. Staining of MLH1, PARP1, XPF, and PAR was associated with recurrence-free survival, and staining of PARP1 and FANCD2 was associated with overall survival on multivariable analysis. Conclusions: DNA repair proteins analyzed by immunohistochemistry may be useful as predictive markers for response to neoadjuvant chemoradiotherapy in patients with esophageal cancer. These results are hypothesis generating and need confirmation in an independent data set.« less

Readability assessment of internet-based patient education materials related to uterine artery embolization.

PubMed

Shukla, Pratik; Sanghvi, Saurin P; Lelkes, Valdis M; Kumar, Abhishek; Contractor, Sohail

2013-04-01

To determine the readability of Internet-based patient education materials (IPEMs) created by United States hospitals and universities and clinical practices and miscellaneous health care-associated Web sites regarding uterine artery embolization (UAE) as a marker for IPEMs in general. Two hundred unique Web sites were evaluated for patient-related articles on UAE. Web sites produced by US hospitals and universities and clinical practices, as well as miscellaneous health care-associated Web sites meeting the Health on the Net Foundation Code of Conduct criteria were included in the database. By using mathematical regression algorithms based on word and sentence length to quantitatively analyze reading materials for language intricacy, readability of 40 UAE-related IPEMs was assessed with four indices: Flesch-Kincaid Grade Level (FKGL), Flesch Reading Ease Score (FRES), Simple Measure of Gobbledygook (SMOG), and Gunning Frequency of Gobbledygook (GFOG). Scores were evaluated against national recommendations, and intergroup analysis was performed. None of the IPEMs were written at or below the sixth-grade reading level, based on FKGL. The mean readability scores were as follows: FRES, 43.98; FKGL, 10.76; SMOG, 13.63; and GFOG, 14.55. These scores indicate that the readability of UAE IPEMs is written at an advanced level, significantly above the recommended 6th grade reading level (P<.05) determined by the United States Department of Health and Human Services. IPEMs related to UAE generated by hospitals, clinical practices, and miscellaneous health care-associated Web sites are written above the recommended sixth grade level. IPEMs for other disease entities may also reflect similar results. Copyright © 2013 SIR. Published by Elsevier Inc. All rights reserved.

Predicting Progression from Mild Cognitive Impairment to Alzheimer's Dementia Using Clinical, MRI, and Plasma Biomarkers via Probabilistic Pattern Classification

PubMed Central

Korolev, Igor O.; Symonds, Laura L.; Bozoki, Andrea C.

2016-01-01

Background Individuals with mild cognitive impairment (MCI) have a substantially increased risk of developing dementia due to Alzheimer's disease (AD). In this study, we developed a multivariate prognostic model for predicting MCI-to-dementia progression at the individual patient level. Methods Using baseline data from 259 MCI patients and a probabilistic, kernel-based pattern classification approach, we trained a classifier to distinguish between patients who progressed to AD-type dementia (n = 139) and those who did not (n = 120) during a three-year follow-up period. More than 750 variables across four data sources were considered as potential predictors of progression. These data sources included risk factors, cognitive and functional assessments, structural magnetic resonance imaging (MRI) data, and plasma proteomic data. Predictive utility was assessed using a rigorous cross-validation framework. Results Cognitive and functional markers were most predictive of progression, while plasma proteomic markers had limited predictive utility. The best performing model incorporated a combination of cognitive/functional markers and morphometric MRI measures and predicted progression with 80% accuracy (83% sensitivity, 76% specificity, AUC = 0.87). Predictors of progression included scores on the Alzheimer's Disease Assessment Scale, Rey Auditory Verbal Learning Test, and Functional Activities Questionnaire, as well as volume/cortical thickness of three brain regions (left hippocampus, middle temporal gyrus, and inferior parietal cortex). Calibration analysis revealed that the model is capable of generating probabilistic predictions that reliably reflect the actual risk of progression. Finally, we found that the predictive accuracy of the model varied with patient demographic, genetic, and clinical characteristics and could be further improved by taking into account the confidence of the predictions. Conclusions We developed an accurate prognostic model for predicting MCI-to-dementia progression over a three-year period. The model utilizes widely available, cost-effective, non-invasive markers and can be used to improve patient selection in clinical trials and identify high-risk MCI patients for early treatment. PMID:26901338

Maternal diets with low healthy eating index or Mediterranean diet adherence scores are associated with high cord-blood insulin levels and insulin resistance markers at birth.

PubMed

Gesteiro, E; Rodríguez Bernal, B; Bastida, S; Sánchez-Muniz, F J

2012-09-01

Few studies have used healthy eating index (HEI) and mediterranean diet adherence (MDA) scores to evaluate the diet quality during pregnancy. To determine the relationship between first trimester diet quality and insulin sensitivity/resistance biomarkers at birth. Cord-blood insulin sensitivity/resistance biomarkers of the offspring of 35 women whose diets were 'adequate' or 'inadequate' according to their HEI score (>70 or ≤ 70, respectively) and their 13-point MDA score (≥ 7 or <7, respectively). Low HEI-score diets contained less (g/1000 kcal) carbohydrates (CHO; P=0.027) and fibre (P=0.011), and more fats (P<0.001) and cholesterol (P<0.001), and contributed (percentage contribution to total energy (%En)) fewer CHO (P=0.005), more fats (P=<0.001) and saturated fatty acid (SFA; P=0.002) than their high HEI-score counterparts. Low MDA-score diets contained less (g/1000 kcal) fibre (P<0.001) and more cholesterol (P=0.05), had lower polyunsaturated fatty acids+monounsaturated fatty acid/SFA (PUFA+MUFA/SFA; P=0.05) and higher SFA/CHO (P=0.021) and ω-6/ω-3 PUFA ratios (P=0.044) than their respective counterparts. Women consuming the low HEI- or low MDA-score diets had low-fasting glycaemia (P=0.016 or P=0.025, respectively) but delivered infants with high insulinaemia (P=0.048 or P=0.017, respectively), homeostatic model assessment for insulin resistance (HOMA-IR; P=0.031 or P=0.049, respectively) and glycaemia (P=0.018 or P=0.048, respectively). The relative risk (RR) of high-neonatal glycaemia and insulinaemia were 7.6 (P=0.008) and 6.7 (P=0.017) for low vs high HEI-score groups. High HOMA-IR and high glucose RR were, respectively, 3.4 (P=0.043) and 3.9 (P=0.016) in neonates from the <7 MDA- vs ≥ 7 MDA-score group. These RRs were not affected by potential confounders. Maternal diets with low HEI- or MDA-scores during the first trimester of pregnancy negatively affect insulin resistance markers at birth.

Use of the Children's Communication Checklist-2 for classification of language impairment risk in young school-age children with attention-deficit/hyperactivity disorder.

PubMed

Timler, Geralyn R

2014-02-01

Children with attention-deficit/hyperactivity disorder (ADHD) are at elevated risk for language impairment (LI). This study examined the feasibility of using the Children's Communication Checklist-2 (CCC-2; Bishop, 2006) to classify risk for LI in young children, ages 5-8 years, with ADHD. Parents of 32 children with ADHD and 12 typically developing peers completed the CCC-2. The Clinical Evaluation of Language Fundamentals, Fourth Edition (Semel, Wiig, & Secord, 2003) and the Test of Narrative Language (Gillam & Pearson, 2004) were administered to diagnose LI. Language samples were collected to examine clinical markers of LI. CCC-2 General Communication Composite scores ≤ 85 correctly classified 10 participants with ADHD diagnosed with LI as defined by composite scores ≤ 85 on the Clinical Evaluation of Language Fundamentals, Fourth Edition, or on the Test of Narrative Language. Five of these participants demonstrated 1 or more clinical markers of LI in language samples. Three additional participants, who received a General Communication Composite score ≤ 85 yet scored above 85 on the language tests, demonstrated CCC-2 profiles suggestive of pragmatic impairment. Sensitivity and specificity rates were 100% and 85.29%, respectively. CCC-2 scores and most measures were significantly correlated. The results support the feasibility of using the CCC-2 as a screener to identify children with ADHD who are at elevated risk for LI and need referral for comprehensive assessment.

Fibro markers for prediction of hepatocellular carcinoma in Egyptian patients with chronic liver disease.

PubMed

Mobarak, Lamiaa; Omran, Dalia; Nabeel, Mohammed M; Zakaria, Zeinab

2017-06-01

It is well known that hepatocellular carcinoma (HCC) develops as a consequence of hepatic fibrosis progression. In this study, we aimed to evaluate the inflammatory and fibrosis markers as predictors for HCC development among patients with hepatitis C virus (HCV) related chronic liver disease to help in early diagnosis and management of HCC. A total of 280 patients with chronic liver disease were included in this retrospective study, out of them 140 had liver cirrhosis with HCC and 140 had cirrhosis without HCC. Eight readily available blood indices King score, Fibro Q, AST-ALT ratio (AAR), APRI, LOK index, Goteborg University Cirrhosis Index (GUCI), fibro alpha, and Biotechnology Research Center (BRC) were constructed to compare the accuracies of these non invasive scores in predicting HCC development. All fibrosis scores except APRI were significantly higher in HCC. We found that Fibro alpha and BRC had superior diagnostic performance in prediction of HCC based on area under curve of 0.91 and 0.93, respectively compared to other scores with area under curve ranged from poor to failure (0.59-0.66). Almost all cirrhotic cases were secondary to HCV (93.6%), while HBV was detected in 2.1% of cases only. Anti-HCV positive was reported in 100% of HCC cases (P = 0.002). Fibro alpha and BRC scores can be used for prediction of HCC. J. Med. Virol. 89:1062-1068, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

High-throughput genotyping of hop (Humulus lupulus L.) utilising diversity arrays technology (DArT).

PubMed

Howard, E L; Whittock, S P; Jakše, J; Carling, J; Matthews, P D; Probasco, G; Henning, J A; Darby, P; Cerenak, A; Javornik, B; Kilian, A; Koutoulis, A

2011-05-01

Implementation of molecular methods in hop (Humulus lupulus L.) breeding is dependent on the availability of sizeable numbers of polymorphic markers and a comprehensive understanding of genetic variation. However, use of molecular marker technology is limited due to expense, time inefficiency, laborious methodology and dependence on DNA sequence information. Diversity arrays technology (DArT) is a high-throughput cost-effective method for the discovery of large numbers of quality polymorphic markers without reliance on DNA sequence information. This study is the first to utilise DArT for hop genotyping, identifying 730 polymorphic markers from 92 hop accessions. The marker quality was high and similar to the quality of DArT markers previously generated for other species; although percentage polymorphism and polymorphism information content (PIC) were lower than in previous studies deploying other marker systems in hop. Genetic relationships in hop illustrated by DArT in this study coincide with knowledge generated using alternate methods. Several statistical analyses separated the hop accessions into genetically differentiated North American and European groupings, with hybrids between the two groups clearly distinguishable. Levels of genetic diversity were similar in the North American and European groups, but higher in the hybrid group. The markers produced from this time and cost-efficient genotyping tool will be a valuable resource for numerous applications in hop breeding and genetics studies, such as mapping, marker-assisted selection, genetic identity testing, guidance in the maintenance of genetic diversity and the directed breeding of superior cultivars.

Varietal Discrimination and Genetic Variability Analysis of Cymbopogon Using RAPD and ISSR Markers Analysis.

PubMed

Bishoyi, Ashok Kumar; Sharma, Anjali; Kavane, Aarti; Geetha, K A

2016-06-01

Cymbopogon is an important genus of family Poaceae, cultivated mainly for its essential oils which possess high medicinal and economical value. Several cultivars of Cymbopogon species are available for commercial cultivation in India and identification of these cultivars was conceded by means of morphological markers and essential oil constitution. Since these parameters are highly influenced by environmental factors, in most of the cases, it is difficult to identify Cymbopogon cultivars. In the present study, Random amplified polymorphic DNA (RAPD) and Inter-simple sequence repeat (ISSR) markers were employed to discriminate nine leading varieties of Cymbopogon since prior genomic information is lacking or very little in the genus. Ninety RAPD and 70 ISSR primers were used which generated 63 and 69 % polymorphic amplicons, respectively. Similarity in the pattern of UPGMA-derived dendrogram of RAPD and ISSR analysis revealed the reliability of the markers chosen for the study. Varietal/cultivar-specific markers generated from the study could be utilised for varietal/cultivar authentication, thus monitoring the quality of the essential oil production in Cymbopogon. These markers can also be utilised for the IPR protection of the cultivars. Moreover, the study provides molecular marker tool kit in both random and simple sequence repeats for diverse molecular research in the same or related genera.

Genome-wide generation and use of informative intron-spanning and intron-length polymorphism markers for high-throughput genetic analysis in rice

PubMed Central

Badoni, Saurabh; Das, Sweta; Sayal, Yogesh K.; Gopalakrishnan, S.; Singh, Ashok K.; Rao, Atmakuri R.; Agarwal, Pinky; Parida, Swarup K.; Tyagi, Akhilesh K.

2016-01-01

We developed genome-wide 84634 ISM (intron-spanning marker) and 16510 InDel-fragment length polymorphism-based ILP (intron-length polymorphism) markers from genes physically mapped on 12 rice chromosomes. These genic markers revealed much higher amplification-efficiency (80%) and polymorphic-potential (66%) among rice accessions even by a cost-effective agarose gel-based assay. A wider level of functional molecular diversity (17–79%) and well-defined precise admixed genetic structure was assayed by 3052 genome-wide markers in a structured population of indica, japonica, aromatic and wild rice. Six major grain weight QTLs (11.9–21.6% phenotypic variation explained) were mapped on five rice chromosomes of a high-density (inter-marker distance: 0.98 cM) genetic linkage map (IR 64 x Sonasal) anchored with 2785 known/candidate gene-derived ISM and ILP markers. The designing of multiple ISM and ILP markers (2 to 4 markers/gene) in an individual gene will broaden the user-preference to select suitable primer combination for efficient assaying of functional allelic variation/diversity and realistic estimation of differential gene expression profiles among rice accessions. The genomic information generated in our study is made publicly accessible through a user-friendly web-resource, “Oryza ISM-ILP marker” database. The known/candidate gene-derived ISM and ILP markers can be enormously deployed to identify functionally relevant trait-associated molecular tags by optimal-resource expenses, leading towards genomics-assisted crop improvement in rice. PMID:27032371

A universal and reliable assay for molecular sex identification of three-spined sticklebacks (Gasterosteus aculeatus).

PubMed

Toli, E-A; Calboli, F C F; Shikano, T; Merilä, J

2016-11-01

In heterogametic species, biological differences between the two sexes are ubiquitous, and hence, errors in sex identification can be a significant source of noise and bias in studies where sex-related sources of variation are of interest or need to be controlled for. We developed and validated a universal multimarker assay for reliable sex identification of three-spined sticklebacks (Gasterosteus aculeatus). The assay makes use of genotype scores from three sex-linked loci and utilizes Bayesian probabilistic inference to identify sex of the genotyped individuals. The results, validated with 286 phenotypically sexed individuals from six populations of sticklebacks representing all major genetic lineages (cf. Pacific, Atlantic and Japan Sea), indicate that in contrast to commonly used single-marker-based sex identification assays, the developed multimarker assay should be 100% accurate. As the markers in the assay can be scored from agarose gels, it provides a quick and cost-efficient tool for universal sex identification of three-spined sticklebacks. The general principle of combining information from multiple markers to improve the reliability of sex identification is transferable and can be utilized to develop and validate similar assays for other species. © 2016 John Wiley & Sons Ltd.

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.

Homozygosity and linkage-disequilibrium mapping of the syndrome of congenital hypoparathyroidism, growth and mental retardation, and dysmorphism to a 1-cM interval on chromosome 1q42-43.

PubMed

Parvari, R; Hershkovitz, E; Kanis, A; Gorodischer, R; Shalitin, S; Sheffield, V C; Carmi, R

1998-07-01

The syndrome of hypoparathyroidism associated with growth retardation, developmental delay, and dysmorphism (HRD) is a newly described, autosomal recessive, congenital disorder with severe, often fatal consequences. Since the syndrome is very rare, with all parents of affected individuals being consanguineous, it is presumed to be caused by homozygous inheritance of a single recessive mutation from a common ancestor. To localize the HRD gene, we performed a genomewide screen using DNA pooling and homozygosity mapping for apparently unlinked kindreds. Analysis of a panel of 359 highly polymorphic markers revealed linkage to D1S235. The maximum LOD score obtained was 4.11 at a recombination fraction of 0. Analysis of three additional markers-GGAA6F06, D1S2678, and D1S179-in a 2-cM interval around D1S235 resulted in LOD scores >3. Analysis of additional chromosome 1 markers revealed evidence of genetic linkage disequilibrium and place the HRD locus within an approximately 1-cM interval defined by D1S1540 and D1S2678 on chromosome 1q42-43.

Homozygosity and linkage-disequilibrium mapping of the syndrome of congenital hypoparathyroidism, growth and mental retardation, and dysmorphism to a 1-cM interval on chromosome 1q42-43.

PubMed Central

Parvari, R; Hershkovitz, E; Kanis, A; Gorodischer, R; Shalitin, S; Sheffield, V C; Carmi, R

1998-01-01

The syndrome of hypoparathyroidism associated with growth retardation, developmental delay, and dysmorphism (HRD) is a newly described, autosomal recessive, congenital disorder with severe, often fatal consequences. Since the syndrome is very rare, with all parents of affected individuals being consanguineous, it is presumed to be caused by homozygous inheritance of a single recessive mutation from a common ancestor. To localize the HRD gene, we performed a genomewide screen using DNA pooling and homozygosity mapping for apparently unlinked kindreds. Analysis of a panel of 359 highly polymorphic markers revealed linkage to D1S235. The maximum LOD score obtained was 4.11 at a recombination fraction of 0. Analysis of three additional markers-GGAA6F06, D1S2678, and D1S179-in a 2-cM interval around D1S235 resulted in LOD scores >3. Analysis of additional chromosome 1 markers revealed evidence of genetic linkage disequilibrium and place the HRD locus within an approximately 1-cM interval defined by D1S1540 and D1S2678 on chromosome 1q42-43. PMID:9634513

The development and mapping of functional markers in Fragaria and their transferability and potential for mapping in other genera.

PubMed

Sargent, D J; Rys, A; Nier, S; Simpson, D W; Tobutt, K R

2007-01-01

We have developed 46 primer pairs from exon sequences flanking polymorphic introns of 23 Fragaria gene sequences and one Malus sequence deposited in the EMBL database. Sequencing of a set of the PCR products amplified with the novel primer pairs in diploid Fragaria showed the products to be homologous to the sequences from which the primers were originally designed. By scoring the segregation of the 24 genes in two diploid Fragaria progenies FV x FN (F. vesca x F. nubicola F(2)) and 815 x 903BC (F. vesca x F. viridis BC(1)) 29 genetic loci at discrete positions on the seven linkage groups previously characterised could be mapped, bringing to 35 the total number of known function genes mapped in Fragaria. Twenty primer pairs, representing 14 genes, amplified a product of the expected size in both Malus and Prunus. To demonstrate the applicability of these gene-specific loci to comparative mapping in Rosaceae, five markers that displayed clear polymorphism between the parents of a Malus and a Prunus mapping population were selected. The markers were then scored and mapped in at least one of the two additional progenies.

Healthcare ethics: The experience after the Haitian earthquake

DTIC Science & Technology

2010-06-01

percent of the indica- tions being acute renal failure presumed secondary to rhabdomyolysis. Early in the mission, it was under- stood that given the nature...mortality. The Sequential Organ Failure Score set at markers to predict 80 percent mortality was obtained on day 1 and day 5. Scores above the 80...have www.disastermedicinejournal.com 1 4 5 chronicled anecdotal reports, but less has been written about the larger Haitian context.8 Although an

Transcriptome Profiles of Isolated Murine Achilles Tendon Proper- and Peritenon- Derived Progenitor Cells.

PubMed

Mienaltowski, Michael J; Cánovas, Angela; Fates, Valerie A; Hampton, Angela R; Pechanec, Monica Y; Islas-Trejo, Alma; Medrano, Juan F

2018-06-21

Progenitor cells of the tendon proper and peritenon have unique properties that could impact their utilization in tendon repair strategies. While a few markers have been found to aid in distinguishing progenitors cells from each region, there is great value in identifying more markers. In this study, we hypothesized that RNAseq could be used to improve our understanding of those markers that define these cell types. Transcriptome profiles were generated for pools of mouse Achilles tendon progenitor cells from both regions and catalogues of potential markers were generated. Moreover, common (e.g., glycoprotein, signaling, and proteinaceous extracellular matrix) and unique (e.g., cartilage development versus angiogenesis and muscle contraction) biological processes and molecular functions were described for progenitors from each region. Real-time quantitative PCR of a subset of genes was used to gain insight into the heterogeneity amongst individual progenitor colonies from each region. Markers like Scx, Mkx, Thbs4, and Wnt10a were consistently able to distinguish tendon proper progenitors from peritenon progenitors; expression variability for other genes suggested greater cell type complexity for potential peritenon progenitor markers. This is the first effort to define Achilles tendon progenitor markers by region. Further efforts to investigate the value of these catalogued markers are required by screening more individual colonies of progenitors for more markers. Findings from this study advance efforts in the discernment of cell type specific markers for tendon proper and peritenon progenitor cells; insight into marker sets could improve tracking and sorting strategies for these cells for future therapeutic strategies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Extraction of Total DNA and RNA from Marine Filter Samples and Generation of a cDNA as Universal Template for Marker Gene Studies.

PubMed

Schneider, Dominik; Wemheuer, Franziska; Pfeiffer, Birgit; Wemheuer, Bernd

2017-01-01

Microbial communities play an important role in marine ecosystem processes. Although the number of studies targeting marker genes such as the 16S rRNA gene has been increased in the last few years, the vast majority of marine diversity is rather unexplored. Moreover, most studies focused on the entire bacterial community and thus disregarded active microbial community players. Here, we describe a detailed protocol for the simultaneous extraction of DNA and RNA from marine water samples and for the generation of cDNA from the isolated RNA which can be used as a universal template in various marker gene studies.

A sex-averaged genetic linkage map in coastal Douglas-fir (Pseudotsuga menziesii [Mirb] Franco var menziesii) based on RFLP and RAPD markers

Treesearch

K.D. Jermstad; D.L. Bassoni; N.C. Wheeler; D.B. Neale

1998-01-01

We have constructed a sex-averaged genetic linkage map in coastal Douglas-fir ( Pseudotsuga menziesii [Mirb.] Franco var menziesii) using a three-generation outcrossed pedigree and molecular markers. Our research objectives are to learn about genome organization and to identify markers associated with adaptive traits. The map...

Public availability of a genotyped, segregating population may foster marker assisted breeding (MAB) and quantitative trait loci (QTL) discovery: An example using strawberry

USDA-ARS?s Scientific Manuscript database

Much of the cost associated with marker discovery for marker assisted breeding (MAB) can be eliminated if a diverse, segregating population is generated, genotyped and made available to the global breeding community. Herein, we present an example of a hybrid, wild-derived family of the octoploid str...

Article surveillance magnetic marker having an hysteresis loop with large Barkhausen discontinuities

DOEpatents

Humphrey, Floyd B.

1987-01-01

A marker for an electronic article surveillance system is disclosed comprising a body of magnetic material with retained stress and having a magnetic hysteresis loop with a large Barkhausen discontinuity such that, upon exposure of the marker to an external magnetic field whose field strength in the direction opposing the instantaneous magnetic polarization of the marker exceeds a predetermined threshold value, there results a regenerative reversal of the magnetic polarization of the marker. An electronic article surveillance system and a method utilizing the marker are also disclosed. Exciting the marker with a low frequency and low field strength, so long as the field strength exceeds the low threshold level for the marker, causes a regenerative reversal of magnetic polarity generating a harmonically rich pulse that is readily detected and easily distinguished.

Next-Generation Sequencing Approaches in Genome-Wide Discovery of Single Nucleotide Polymorphism Markers Associated with Pungency and Disease Resistance in Pepper.

PubMed

Manivannan, Abinaya; Kim, Jin-Hee; Yang, Eun-Young; Ahn, Yul-Kyun; Lee, Eun-Su; Choi, Sena; Kim, Do-Sun

2018-01-01

Pepper is an economically important horticultural plant that has been widely used for its pungency and spicy taste in worldwide cuisines. Therefore, the domestication of pepper has been carried out since antiquity. Owing to meet the growing demand for pepper with high quality, organoleptic property, nutraceutical contents, and disease tolerance, genomics assisted breeding techniques can be incorporated to develop novel pepper varieties with desired traits. The application of next-generation sequencing (NGS) approaches has reformed the plant breeding technology especially in the area of molecular marker assisted breeding. The availability of genomic information aids in the deeper understanding of several molecular mechanisms behind the vital physiological processes. In addition, the NGS methods facilitate the genome-wide discovery of DNA based markers linked to key genes involved in important biological phenomenon. Among the molecular markers, single nucleotide polymorphism (SNP) indulges various benefits in comparison with other existing DNA based markers. The present review concentrates on the impact of NGS approaches in the discovery of useful SNP markers associated with pungency and disease resistance in pepper. The information provided in the current endeavor can be utilized for the betterment of pepper breeding in future.

Characterizing proton-activated materials to develop PET-mediated proton range verification markers

NASA Astrophysics Data System (ADS)

Cho, Jongmin; Ibbott, Geoffrey S.; Kerr, Matthew D.; Amos, Richard A.; Stingo, Francesco C.; Marom, Edith M.; Truong, Mylene T.; Palacio, Diana M.; Betancourt, Sonia L.; Erasmus, Jeremy J.; DeGroot, Patricia M.; Carter, Brett W.; Gladish, Gregory W.; Sabloff, Bradley S.; Benveniste, Marcelo F.; Godoy, Myrna C.; Patil, Shekhar; Sorensen, James; Mawlawi, Osama R.

2016-06-01

Conventional proton beam range verification using positron emission tomography (PET) relies on tissue activation alone and therefore requires particle therapy PET whose installation can represent a large financial burden for many centers. Previously, we showed the feasibility of developing patient implantable markers using high proton cross-section materials (18O, Cu, and 68Zn) for in vivo proton range verification using conventional PET scanners. In this technical note, we characterize those materials to test their usability in more clinically relevant conditions. Two phantoms made of low-density balsa wood (~0.1 g cm-3) and beef (~1.0 g cm-3) were embedded with Cu or 68Zn foils of several volumes (10-50 mm3). The metal foils were positioned at several depths in the dose fall-off region, which had been determined from our previous study. The phantoms were then irradiated with different proton doses (1-5 Gy). After irradiation, the phantoms with the embedded foils were moved to a diagnostic PET scanner and imaged. The acquired data were reconstructed with 20-40 min of scan time using various delay times (30-150 min) to determine the maximum contrast-to-noise ratio. The resultant PET/computed tomography (CT) fusion images of the activated foils were then examined and the foils’ PET signal strength/visibility was scored on a 5 point scale by 13 radiologists experienced in nuclear medicine. For both phantoms, the visibility of activated foils increased in proportion to the foil volume, dose, and PET scan time. A linear model was constructed with visibility scores as the response variable and all other factors (marker material, phantom material, dose, and PET scan time) as covariates. Using the linear model, volumes of foils that provided adequate visibility (score 3) were determined for each dose and PET scan time. The foil volumes that were determined will be used as a guideline in developing practical implantable markers.

Development of microsatellite markers using next-generation sequencing for the columnar cactus Echinopsis chiloensis (Cactaceae).

PubMed

Ossa, Carmen G; Larridon, Isabel; Peralta, Gioconda; Asselman, Pieter; Pérez, Fernanda

2016-12-01

The aim of this study was to develop microsatellite markers as a tool to study population structure, genetic diversity and effective population size of Echinopsis chiloensis, an endemic cactus from arid and semiarid regions of Central Chile. We developed 12 polymorphic microsatellite markers for E. chiloensis using next-generation sequencing and tested them in 60 individuals from six sites, covering all the latitudinal range of this species. The number of alleles per locus ranged from 3 to 8, while the observed (Ho) and expected (He) heterozygosity ranged from 0.0 to 0.80 and from 0.10 to 0.76, respectively. We also detected significant differences between sites, with F ST values ranging from 0.05 to 0.29. Microsatellite markers will enable us to estimate genetic diversity and population structure of E. chiloensis in future ecological and phylogeographic studies.

New development and validation of 50 SSR markers in breadfruit (Artocarpus altilis, Moraceae) by next-generation sequencing.

PubMed

De Bellis, Fabien; Malapa, Roger; Kagy, Valérie; Lebegin, Stéphane; Billot, Claire; Labouisse, Jean-Pierre

2016-08-01

Using next-generation sequencing technology, new microsatellite loci were characterized in Artocarpus altilis (Moraceae) and two congeners to increase the number of available markers for genotyping breadfruit cultivars. A total of 47,607 simple sequence repeat loci were obtained by sequencing a library of breadfruit genomic DNA with an Illumina MiSeq system. Among them, 50 single-locus markers were selected and assessed using 41 samples (39 A. altilis, one A. camansi, and one A. heterophyllus). All loci were polymorphic in A. altilis, 44 in A. camansi, and 21 in A. heterophyllus. The number of alleles per locus ranged from two to 19. The new markers will be useful for assessing the identity and genetic diversity of breadfruit cultivars on a small geographical scale, gaining a better understanding of farmer management practices, and will help to optimize breadfruit genebank management.

A Diagnostic Marker to Discriminate Childhood Apraxia of Speech From Speech Delay: II. Validity Studies of the Pause Marker.

PubMed

Shriberg, Lawrence D; Strand, Edythe A; Fourakis, Marios; Jakielski, Kathy J; Hall, Sheryl D; Karlsson, Heather B; Mabie, Heather L; McSweeny, Jane L; Tilkens, Christie M; Wilson, David L

2017-04-14

The purpose of this 2nd article in this supplement is to report validity support findings for the Pause Marker (PM), a proposed single-sign diagnostic marker of childhood apraxia of speech (CAS). PM scores and additional perceptual and acoustic measures were obtained from 296 participants in cohorts with idiopathic and neurogenetic CAS, adult-onset apraxia of speech and primary progressive apraxia of speech, and idiopathic speech delay. Adjusted for questionable specificity disagreements with a pediatric Mayo Clinic diagnostic standard, the estimated sensitivity and specificity, respectively, of the PM were 86.8% and 100% for the CAS cohort, yielding positive and negative likelihood ratios of 56.45 (95% confidence interval [CI]: [1.15, 2763.31]) and 0.13 (95% CI [0.06, 0.30]). Specificity of the PM for 4 cohorts totaling 205 participants with speech delay was 98.5%. These findings are interpreted as providing support for the PM as a near-conclusive diagnostic marker of CAS.

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

Professional involvement is associated with increased job satisfaction among dietitians.

PubMed

Mortensen, Jenny K; Nyland, Nora K; Fullmer, Susan; Eggett, Dennis L

2002-10-01

This study explored a relationship between professional involvement and job satisfaction among dietitians. A random sample of 2,600 employed registered dietitians (RDs) received a 55-item questionnaire including a standardized measure of job satisfaction. The response rate was 67.3%; 50.8% were useable (n = 1,321). Ninety-two percent of RDs reported job satisfaction. The mean score was 68.8 +/- .28 (possible range: 18-90), with scores over 54 indicating job satisfaction. A positive relationship was found between job satisfaction and markers of professional involvement. Additionally, six characteristics related to professional involvement were: having had a mentor, being a mentor, self-assessed high professional involvement, full-time employment, high annual income, and increased hours worked per week. There was also a positive relationship between markers of professional involvement and employer support. We conclude that, overall, RDs are satisfied with their jobs and that greater professional involvement is related to greater job satisfaction.

Expression and significance of Ki-67 in lung cancer.

PubMed

Folescu, Roxana; Levai, Codrina Mihaela; Grigoraş, Mirela Loredana; Arghirescu, Teodora Smaranda; Talpoş, Ioana Cristina; Gîndac, Ciprian Mihai; Zamfir, Carmen Lăcrămioara; Poroch, Vladimir; Anghel, Mirella Dorina

2018-01-01

Ki-67 parameter is a proliferation marker in malignant tumors. The increased proliferation activity and the decreased prognosis in lung cancer determined us to investigate different parameters connected to the tumor's aggression, such as cellularity, Ki-67 positivity rate, and proliferating cell nuclear antigen (PCNA). We evaluated the proliferative activity in 62 primary lung tumors by determining the cell's percentage of Ki-67 and immunoreactive PCNA (using MIB-1 and PCNA monoclonal antibodies), classifying Ki-67 and PCNA immunoreactivity into three score groups. The results obtained emphasized a linkage between Ki-67 score with the histological tumor subtype, tumor cellularity and degree of differentiation and with other proliferation immunohistochemistry (IHC) markers, such as p53 cellular tumor antigen. The tumor's cellularity, the Ki-67 positivity rate and PCNA, together with the clinical stage and the histological differentiation bring extra pieces of useful information in order to anticipate the evolution and the prognosis of lung cancer.

Descent graphs in pedigree analysis: applications to haplotyping, location scores, and marker-sharing statistics.

PubMed Central

Sobel, E.; Lange, K.

1996-01-01

The introduction of stochastic methods in pedigree analysis has enabled geneticists to tackle computations intractable by standard deterministic methods. Until now these stochastic techniques have worked by running a Markov chain on the set of genetic descent states of a pedigree. Each descent state specifies the paths of gene flow in the pedigree and the founder alleles dropped down each path. The current paper follows up on a suggestion by Elizabeth Thompson that genetic descent graphs offer a more appropriate space for executing a Markov chain. A descent graph specifies the paths of gene flow but not the particular founder alleles traveling down the paths. This paper explores algorithms for implementing Thompson's suggestion for codominant markers in the context of automatic haplotyping, estimating location scores, and computing gene-clustering statistics for robust linkage analysis. Realistic numerical examples demonstrate the feasibility of the algorithms. PMID:8651310

Evaluation of Accessory Lacrimal Gland in Muller's Muscle Conjunctival Resection Specimens for Precursor Cell Markers and Biological Markers of Dry Eye Disease.

PubMed

Ali, Marwan; Shah, Dhara; Pasha, Zeeshan; Jassim, Sarmad H; Jassim Jaboori, Assraa; Setabutr, Pete; Aakalu, Vinay K

2017-04-01

The accessory lacrimal glands (ALGs) are an understudied component of the tear functional unit, even though they are important in the development of dry eye syndrome (DES). To advance our understanding of aging changes, regenerative potential, and histologic correlates to human characteristics, we investigated human ALG tissue from surgical samples to determine the presence or absence of progenitor cell markers and lacrimal epithelial markers and to correlate marker expression to relevant patient characteristics. ALG tissues obtained from Muller's muscle conjunctival resection (MMCR) specimens were created using tissue microarrays (TMAs). Immunofluorescence staining of MMCR sections was performed using primary antibodies specific to cell protein markers. Cell marker localization in TMAs was then assessed by two blinded observers using a standardized scoring system. Patient characteristics including age, race, and status of ocular surface health were then compared against expression of stem cell markers. Human ALG expressed a number of epithelial markers, and in particular, histatin-1 was well correlated with the expression of epithelial markers and was present in most acini. In addition, we noted the presence of precursor cell markers nestin, ABCG2, and CD90 in ALG tissue. There was a decrease in precursor cell marker expression with increasing age. Finally, we noted that a negative association was present between histatin-1 expression and DES. Thus, we report for the first time that human ALG tissues contain precursor marker-positive cells and that this marker expression may decrease with increasing age. Moreover, histatin-1 expression may be decreased in DES. Future studies will be performed to use these cell markers to isolate and culture lacrimal epithelial cells from heterogeneous tissues, determine the relevance of histatin-1 expression to DES, and isolate candidate precursor cells from ALG tissue.

Introgression of heat shock protein (Hsp70 and sHsp) genes into the Malaysian elite chilli variety Kulai (Capsicum annuum L.) through the application of marker-assisted backcrossing (MAB).

PubMed

Usman, Magaji G; Rafii, Mohd Y; Martini, Mohammad Y; Yusuff, Oladosu A; Ismail, Mohd R; Miah, Gous

2018-03-01

Backcrossing together with simple sequence repeat marker strategy was adopted to improve popular Malaysian chilli Kulai (Capsicum annuum L.) for heat tolerance. The use of molecular markers in backcross breeding and selection contributes significantly to overcoming the main drawbacks such as increase linkage drag and time consumption, in the ancient manual breeding approach (conventional), and speeds up the genome recovery of the recurrent parent. The strategy was adopted to introgress heat shock protein gene(s) from AVPP0702 (C. annuum L.), which are heat-tolerant, into the genetic profile of Kulai, a popular high-yielding chilli but which is heat sensitive. The parents were grown on seed trays, and parental screening was carried out with 252 simple sequence repeat markers. The selected parents were crossed and backcrossed to generate F 1 hybrids and backcross generations. Sixty-eight markers appeared to be polymorphic and were used to assess the backcross generation; BC 1 F 1 , BC 2 F 1 and BC 3 F 1 . The average recipient allele of the selected four BC 1 F 1 plants was 80.75% which were used to produce the BC 2 F 1 generation. BC 1 -P 7 was the best BC 1 F 1 plant because it had the highest recovery at 83.40% and was positive to Hsp-linked markers (Hsp70-u2 and AGi42). After three successive generations of backcrossing, the average genome recovery of the recurrent parent in the selected plants in BC 3 F 1 was 95.37%. Hsp gene expression analysis was carried out on BC 1 F 1 , BC 2 F 1 and BC 3 F 1 selected lines. The Hsp genes were found to be up-regulated when exposed to heat treatment. The pattern of Hsp expression in the backcross generations was similar to that of the donor parent. This confirms the successful introgression of a stress-responsive gene (Hsp) into a Kulai chilli pepper variety. Furthermore, the yield performance viz. plant height, number of fruits, fruit length and weight and total yield of the improved plant were similar with the recurrent parent except that the plant height was significantly lower than the Kulai (recurrent) parent.

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.

Neurofibromatosis type 2 appears to be a genetically homogeneous disease

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

Narod, S.A.; Parry, D.M.; Parboosingh, J.

Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome characterized by the development of vestibular schwannomas and other tumors of the nervous system, including cranial and spinal meningiomos, schwannomas, and ependymomas. The presence of bilateral vestibular schwannomas is sufficient for the diagnosis. Skin manifestations are less common than in neurofibromatosis type 1 (NF1; von Recklinghausen disease). The apparent clinical distinction between NF1 and NF2 has been confirmed at the level of the gene locus by linkage studies; the gene for NF1 maps to chromosome 17, where as the gene for NF2 has been assigned (in a single family) to chromosomemore » 22. To increase the precision of the genetic mapping of NF2 and to determine whether additional susceptibility loci exist, the authors have performed linkage analysis on 12 families with NF2 by using four polymorphic markers from chromosome 22 and a marker at the NF1 locus on chromosome 17. The results confirm the assignment of the gene for NF2 to chromosome 22 and do not support the hypothesis of genetic heterogeneity. The authors believe that chromosome 22 markers can now be used for presymptomatic diagnosis in selected families. The NF2 gene is tightly linked to the D22S32 locus (maximum lod score 4.12; recombination fraction 0). A CA-repeat polymorphism at the CRYB2 locus was the most informative marker in the families (lod score 5.99), but because the observed recombination fraction between NF2 and CRYB2 was 10 cM, predictions using this marker will need to be interpreted with caution. 42 refs., 4 figs., 3 tabs.« less

[Comparison of various noninvasive serum markers of liver fibrosis in chronic viral liver disease].

PubMed

Kim, Sun Min; Sohn, Joo Hyun; Kim, Tae Yeob; Roh, Young Wook; Eun, Chang Soo; Jeon, Yong Cheol; Han, Dong Soo; Oh, Young Ha

2009-12-01

The aim of this study was to determine the clinical performances of noninvasive serum markers for the prediction of liver fibrosis in chronic viral liver diseases. We analyzed a total of 225 patients with chronic viral liver diseases (180 with hepatitis B virus, 43 with hepatitis C virus, and 2 with hepatitis B+C virus) who underwent a liver biopsy procedure at the Hanyang University Guri Hospital between March 2002 and February 2007. Serum was also obtained at the time of liver biopsy. Liver fibrosis was staged according to the scoring system proposed by the Korean Study Group for the Pathology of Digestive Diseases. Various noninvasive serum markers were evaluated, including the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), age-platelet (AP) index, AST/platelet ratio index (APRI), cirrhosis discriminant score (CDS), platelet count, hyaluronic acid (HA), and type IV collagen. There were 17, 40, 61, 74, and 33 patients at stages F0, F1, F2, F3, and F4, respectively. The overall diagnostic accuracies of each marker, as determined by the area under receiver operating characteristics curves, were APRI=0.822, CDS=0.776, platelet count=0.773, AP index=0.756, HA=0.749, type IV collagen=0.718, and AAR=0.642 for predicting significant fibrosis (> or =F2); and CDS=0.835, platelet count=0.795, AP index=0.794, HA=0.766, AAR=0.711, type IV collagen=0.697, and APRI=0.691 for predicting extensive fibrosis (> or =F3). All noninvasive serum markers evaluated in this study were useful for predicting significant or extensive liver fibrosis in chronic viral liver diseases. In particular, APRI was most useful for the prediction of significant fibrosis, and CDS was most useful for the prediction of extensive fibrosis.

Impact of a community based health-promotion programme in 2- to 9-year-old children in Europe on markers of the metabolic syndrome, the IDEFICS study.

PubMed

Mårild, S; Russo, P; Veidebaum, T; Tornaritis, M; De Henauw, S; De Bourdeaudhuij, I; Molnár, D; Moreno, L A; Bramsved, R; Peplies, J; Ahrens, W

2015-12-01

One objective of 'Identification and prevention of Dietary-and lifestyle-induced health EFfects In Children and infantS', the IDEFICS study, was to implement a community-oriented childhood obesity prevention intervention in eight European countries. To assess the effect of an obesity primary prevention programme on metabolic markers. The study had a non-randomized cluster-experimental design. In each country, children were recruited from distinct communities serving as intervention and control regions. Health examinations were done during 2007-2008 before the intervention (T0 ) and during 2009-2010 (T1 ). Children with results available from T0 and T1 on blood pressure, waist circumference and at least one blood-marker (fasting glucose, insulin, HOMA-IR, HbA1c, HDL- and LDL-cholesterol, triglycerides, C-reactive protein) were included. A metabolic syndrome (MetS) score was calculated. A total of 7,406 children (age 2-9.9 years) of the 16,228 participating at T0 provided the necessary data. No effect of the intervention was seen on insulin, HOMA-IR, CRP or the MetS score. Overall fasting glucose increased less in the intervention than in the control region, a pattern driven by three of the eight countries and more pronounced in children of parents with low education. Overall, HbA1c and waist circumference increased more and blood pressure less in the intervention regions. We observed no convincing effect of the intervention on markers of the metabolic syndrome. We identified diverse patterns of change for several markers of uncertain relation to the intervention. © 2015 World Obesity.

CXCL13 is an activity marker for systemic, but not cutaneous lupus erythematosus: a longitudinal cohort study.

PubMed

Niederkorn, Anna; Frühauf, Julia; Schwantzer, Gerold; Wutte, Nora; Painsi, Clemens; Werner, Stefan; Stradner, Martin; Berghold, Andrea; Hermann, Josef; Aberer, Elisabeth

2018-05-04

Serum levels of the IFN-regulated cytokine CXCL13 have been found to correlate with SLEDAI and renal involvement in systemic lupus erythematosus. This study investigates whether CXCL13 can also be a marker of disease activity in patients with subacute cutaneous or chronic cutaneous lupus erythematosus (SCLE, CCLE). We analysed CXCL13 levels in 60 patients' sera (18 SLE, 19 SCLE, 23 CCLE) at five time points within 1 year and correlated these levels with disease activity scores and laboratory markers. Clinical scores with no/mild, moderate or high/severe disease activity were categorized by SLEDAI in SLE, by CLASI in SCLE/CCLE. CXCL13 levels were significantly higher in SLE (median 122.5, IQR 88.0-239.0 pg/ml) than in CCLE patients (median 69.0, IQR 60.0-102.0 pg/ml) (p = 0.006). CXCL13 levels were elevated in 59% (41/70) of SLE patient visits with mild or no disease activity, but in 90% (9/10) with high disease activity. CXCL13 levels correlated with ECLAM, dsDNA-antibodies, and inversely with complement factors C3 and C4 in SLE, and with IgA and ESR in SCLE. In CCLE CXCL13 did not correlate with CLASI or laboratory markers. One SCLE and two CCLE patients with CXCL13 levels > 500 pg/ml had conversion to SLE or an underlying autoimmune disease. CXCL13 seems to be a useful marker of disease activity in SLE, but not in SCLE and CCLE. Conversion from normal to elevated CXCL13 may indicate a flare of SLE. Whether high CXCL13 levels in cutaneous LE indicate the development of SLE should be further investigated.

Markers of Bone Metabolism Are Affected by Renal Function and Growth Hormone Therapy in Children with Chronic Kidney Disease

PubMed Central

Doyon, Anke; Fischer, Dagmar-Christiane; Bayazit, Aysun Karabay; Canpolat, Nur; Duzova, Ali; Sözeri, Betül; Bacchetta, Justine; Balat, Ayse; Büscher, Anja; Candan, Cengiz; Cakar, Nilgun; Donmez, Osman; Dusek, Jiri; Heckel, Martina; Klaus, Günter; Mir, Sevgi; Özcelik, Gül; Sever, Lale; Shroff, Rukshana; Vidal, Enrico; Wühl, Elke; Gondan, Matthias; Melk, Anette; Querfeld, Uwe; Haffner, Dieter; Schaefer, Franz

2015-01-01

Objectives The extent and relevance of altered bone metabolism for statural growth in children with chronic kidney disease is controversial. We analyzed the impact of renal dysfunction and recombinant growth hormone therapy on a panel of serum markers of bone metabolism in a large pediatric chronic kidney disease cohort. Methods Bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), sclerostin and C-terminal FGF-23 (cFGF23) normalized for age and sex were analyzed in 556 children aged 6–18 years with an estimated glomerular filtration rate (eGFR) of 10–60 ml/min/1.73m2. 41 children receiving recombinant growth hormone therapy were compared to an untreated matched control group. Results Standardized levels of BAP, TRAP5b and cFGF-23 were increased whereas sclerostin was reduced. BAP was correlated positively and cFGF-23 inversely with eGFR. Intact serum parathormone was an independent positive predictor of BAP and TRAP5b and negatively associated with sclerostin. BAP and TRAP5B were negatively affected by increased C-reactive protein levels. In children receiving recombinant growth hormone, BAP was higher and TRAP5b lower than in untreated controls. Sclerostin levels were in the normal range and higher than in untreated controls. Serum sclerostin and cFGF-23 independently predicted height standard deviation score, and BAP and TRAP5b the prospective change in height standard deviation score. Conclusion Markers of bone metabolism indicate a high-bone turnover state in children with chronic kidney disease. Growth hormone induces an osteoanabolic pattern and normalizes osteocyte activity. The osteocyte markers cFGF23 and sclerostin are associated with standardized height, and the markers of bone turnover predict height velocity. PMID:25659076

Osteoprotegerin in pregnant adolescents differs by race and is related to infant birth weight z-score

PubMed Central

Essley, B.; McNanley, T.; Cooper, B.; McIntyre, A.; Witter, F.; Harris, Z.; O’Brien, K.

2014-01-01

Osteoprotegerin (OPG) is involved in the regulation of bone turnover, but little is known about this protein during pregnancy or among neonates. We undertook a prospective longitudinal study to identify relationships between OPG, markers of bone turnover and birth outcomes in 155 pregnant adolescents (13–18 years) and their newborns. Maternal blood samples were collected at mid-gestation and at delivery. Cord blood was obtained at delivery. Serum OPG, estradiol and markers of bone formation (osteocalcin) and resorption (N-telopeptide) were assessed in all samples. Placental OPG expression was assessed in placental tissue obtained at delivery. Bone markers and OPG increased significantly from mid-gestation (26.0 ± 3.4 weeks) to delivery (39.3 ± 2.6 weeks). Neonatal OPG was significantly lower, but bone turnover markers were significantly higher than maternal values at mid-gestation and at parturition (P < 0.001). African-American adolescents had higher concentrations of OPG than Caucasian adolescents at mid-gestation (P = 0.01) and delivery (P = 0.04). Gestational age and estradiol were also predictors of maternal OPG at mid-gestation and delivery. OPG concentrations in cord blood were correlated with maternal OPG concentrations and were negatively associated with infant birth weight z-score (P = 0.02) and ponderal index (P = 0.02). In conclusion, maternal OPG concentrations increased across gestation and were significantly higher than neonatal OPG concentrations. Maternal and neonatal OPG concentrations were not associated with markers of bone turnover or placental OPG expression, but neonatal OPG was inversely associated with neonatal anthropometric measures. Additional research is needed to identify roles of OPG during pregnancy. PMID:25141264

Osteopenia in anorexia nervosa: specific mechanisms of bone loss.

PubMed

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

1999-01-01

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

Unhealthy lifestyle may increase later depression via inflammation in older women but not men.

PubMed

Hiles, Sarah A; Baker, Amanda L; de Malmanche, Theo; McEvoy, Mark; Boyle, Michael; Attia, John

2015-04-01

Depression and inflammatory markers have a reliable cross-sectional association although less is known about the prospective relationship. The current study investigated whether pro-inflammatory markers are prospectively associated with depression, and whether indicators of unhealthy lifestyle, physical health and psychosocial functioning may drive this association. Participants were drawn from the Hunter Community Study, a community-dwelling cohort of individuals aged 55-85 years (N = 1410). Participants completed baseline physiological assessment, health-related questionnaires, and blood sampling for the analysis of inflammatory markers, C-reactive protein (CRP) and interleukin (IL)-6. Participants completed the same depressive symptom questionnaire again after 3.5-5.5 years. Depression outcomes at follow-up were analysed dichotomously using established scale cut-off scores and continuously as a "residual score", representing the variation in follow-up depressive symptoms not explained by baseline symptoms and age. Analyses were conducted on males and females separately. At baseline, indicators of unhealthy lifestyle, physical health and psychosocial functioning were associated with depressive symptoms and inflammatory markers. For males, there were no relationships between inflammatory markers and follow-up depression outcomes. In females, IL-6 was significantly associated with depression outcomes in univariate, but not multivariate analyses. However, IL-6 significantly mediated the association between the predictors of waist-to-hip ratio, smoking and psychological coping at baseline, and follow-up depression outcomes. The results support the inflammatory hypothesis of depression, although females may be more vulnerable to effects. The findings raise the possibility that unhealthy lifestyle and psychosocial stress may drive inflammation and subsequent depressive symptoms. Copyright © 2015 Elsevier Ltd. All rights reserved.

Predicting the severity of systemic inflammatory response syndrome (SIRS)-associated coagulopathy with hemostatic molecular markers and vascular endothelial injury markers.

PubMed

Iba, Toshiaki; Gando, Satoshi; Murata, Atsuo; Kushimoto, Shigeki; Saitoh, Daizoh; Eguchi, Yutaka; Ohtomo, Yasuhiro; Okamoto, Kohji; Koseki, Kazuhide; Mayumi, Toshihiko; Ikeda, Toshiaki; Ishhikura, Hiroyasu; Ueyama, Masashi; Ogura, Yuji; Endo, Shigeatsu; Shimazaki, Shuji

2007-11-01

The changes in biomarkers of coagulation or fibrinolysis, anticoagulation, inflammation, and endothelial damage occur in patients with systemic inflammatory response syndrome (SIRS). The purpose of this study is to assess the prognostic value of these markers in patients with SIRS-associated hypercoagulopathy. Sixty-six SIRS patients with a platelet count less than 15.0 x 10(4)/mm3 in three university hospital intensive care units were enrolled in this prospective, comparative study. Blood samples were obtained on day 0 and day 2. Twelve hemostatic, inflammatory, and vascular endothelial indices were measured and the data were compared between the severe group (patients with a total maximum Sequential Organ Failure Assessment score of 10 or more and nonsurvivors; n = 25) and the less-severe group (Sequential Organ Failure Assessment score <10; n = 41). Significant changes between the groups were observed in platelet count, fibrin or fibrinogen degradation products, interleukin-6, soluble thrombomodulin, antithrombin (AT) activity, and protein C activity, both on day 0 and on day 2. In contrast, the d-dimer, soluble fibrin, plasmin-[alpha]2-antiplasmin complex, and E-selectin levels were higher in the severe group only on day 2. No significant difference was seen regarding the thrombin-AT complex and total plasminogen activator inhibitor on both days. A comparison of the areas under the receiver operating characteristic curve revealed the AT activity to be the best predictor of a progression of organ dysfunction. The changes in some hemostatic molecular markers and vascular endothelial markers were conspicuous in patients with organ dysfunction. The AT activity is considered to be the most useful predictor of organ dysfunction.

GlycA, a novel marker of inflammation, is elevated in systemic lupus erythematosus.

PubMed

Chung, C P; Ormseth, M J; Connelly, M A; Oeser, A; Solus, J F; Otvos, J D; Raggi, P; Stein, C M

2016-03-01

GlycA is a novel marker of systemic inflammation detected by nuclear magnetic resonance (NMR) spectroscopy. In the general population, GlycA is correlated with inflammatory markers such as C-reactive protein (CRP) and associated with coronary heart disease and diabetes. The utility of GlycA in patients with systemic lupus erythematosus (SLE) has not been defined. Therefore, we tested the hypothesis that GlycA concentrations are elevated in patients with SLE and associated with other markers of inflammation and coronary atherosclerosis. We compared concentrations of GlycA, detected by NMR, in 116 patients with SLE and 84 control subjects frequency-matched for age, sex, and race. SLE disease activity index (SLEDAI) and the SLE Collaborating Clinics damage index (SLICC) were calculated. Acute phase reactants, a panel of cytokines, and a lipid panel were measured. Electron beam computer tomography (EBCT) was used to quantify coronary artery calcification, a measure of coronary artery atherosclerosis. Patients with SLE had higher concentrations of GlycA (398 (350-445)) than control subjects (339 (299-391)) µmol/L, p < 0.001. In patients with SLE, concentrations of GlycA were significantly associated with sedimentation rate (rho = 0.43), C-reactive protein (rho = 0.59), e-selectin (rho = 0.28), intracellular adhesion molecule-1 (rho = 0.30), triglycerides (rho = 0.45), all p < 0.0023 to account for multiple comparisons, but not with creatinine, SLEDAI, SLICC, or coronary calcium scores. Concentrations of GlycA are higher in patients with SLE than control subjects and associated with markers of inflammation but not with SLE disease activity or chronicity scores or coronary artery calcification. © The Author(s) 2015.

Extension of the lod score: the mod score.

PubMed

Clerget-Darpoux, F

2001-01-01

In 1955 Morton proposed the lod score method both for testing linkage between loci and for estimating the recombination fraction between them. If a disease is controlled by a gene at one of these loci, the lod score computation requires the prior specification of an underlying model that assigns the probabilities of genotypes from the observed phenotypes. To address the case of linkage studies for diseases with unknown mode of inheritance, we suggested (Clerget-Darpoux et al., 1986) extending the lod score function to a so-called mod score function. In this function, the variables are both the recombination fraction and the disease model parameters. Maximizing the mod score function over all these parameters amounts to maximizing the probability of marker data conditional on the disease status. Under the absence of linkage, the mod score conforms to a chi-square distribution, with extra degrees of freedom in comparison to the lod score function (MacLean et al., 1993). The mod score is asymptotically maximum for the true disease model (Clerget-Darpoux and Bonaïti-Pellié, 1992; Hodge and Elston, 1994). Consequently, the power to detect linkage through mod score will be highest when the space of models where the maximization is performed includes the true model. On the other hand, one must avoid overparametrization of the model space. For example, when the approach is applied to affected sibpairs, only two constrained disease model parameters should be used (Knapp et al., 1994) for the mod score maximization. It is also important to emphasize the existence of a strong correlation between the disease gene location and the disease model. Consequently, there is poor resolution of the location of the susceptibility locus when the disease model at this locus is unknown. Of course, this is true regardless of the statistics used. The mod score may also be applied in a candidate gene strategy to model the potential effect of this gene in the disease. Since, however, it ignores the information provided both by disease segregation and by linkage disequilibrium between the marker alleles and the functional disease alleles, its power of discrimination between genetic models is weak. The MASC method (Clerget-Darpoux et al., 1988) has been designed to address more efficiently the objectives of a candidate gene approach.

Development of microsatellite markers from an enriched genomic library for genetic analysis of melon (Cucumis melo L.)

PubMed Central

Ritschel, Patricia Silva; Lins, Tulio Cesar de Lima; Tristan, Rodrigo Lourenço; Buso, Gláucia Salles Cortopassi; Buso, José Amauri; Ferreira, Márcio Elias

2004-01-01

Background Despite the great advances in genomic technology observed in several crop species, the availability of molecular tools such as microsatellite markers has been limited in melon (Cucumis melo L.) and cucurbit species. The development of microsatellite markers will have a major impact on genetic analysis and breeding of melon, especially on the generation of marker saturated genetic maps and implementation of marker assisted breeding programs. Genomic microsatellite enriched libraries can be an efficient alternative for marker development in such species. Results Seven hundred clones containing microsatellite sequences from a Tsp-AG/TC microsatellite enriched library were identified and one-hundred and forty-four primer pairs designed and synthesized. When 67 microsatellite markers were tested on a panel of melon and other cucurbit accessions, 65 revealed DNA polymorphisms among the melon accessions. For some cucurbit species, such as Cucumis sativus, up to 50% of the melon microsatellite markers could be readily used for DNA polymophism assessment, representing a significant reduction of marker development costs. A random sample of 25 microsatellite markers was extracted from the new microsatellite marker set and characterized on 40 accessions of melon, generating an allelic frequency database for the species. The average expected heterozygosity was 0.52, varying from 0.45 to 0.70, indicating that a small set of selected markers should be sufficient to solve questions regarding genotype identity and variety protection. Genetic distances based on microsatellite polymorphism were congruent with data obtained from RAPD marker analysis. Mapping analysis was initiated with 55 newly developed markers and most primers showed segregation according to Mendelian expectations. Linkage analysis detected linkage between 56% of the markers, distributed in nine linkage groups. Conclusions Genomic library microsatellite enrichment is an efficient procedure for marker development in melon. One-hundred and forty-four new markers were developed from Tsp-AG/TC genomic library. This is the first reported attempt of successfully using enriched library for microsatellite marker development in the species. A sample of the microsatellite markers tested proved efficient for genetic analysis of melon, including genetic distance estimates and identity tests. Linkage analysis indicated that the markers developed are dispersed throughout the genome and should be very useful for genetic analysis of melon. PMID:15149552

Heterozygous Mapping Strategy (HetMappS) for High Resolution Genotyping-By-Sequencing Markers: A Case Study in Grapevine

PubMed Central

Wang, Minghui; Londo, Jason P.; Acharya, Charlotte B.; Mitchell, Sharon E.; Sun, Qi; Reisch, Bruce; Cadle-Davidson, Lance

2015-01-01

Genotyping by sequencing (GBS) provides opportunities to generate high-resolution genetic maps at a low genotyping cost, but for highly heterozygous species, missing data and heterozygote undercalling complicate the creation of GBS genetic maps. To overcome these issues, we developed a publicly available, modular approach called HetMappS, which functions independently of parental genotypes and corrects for genotyping errors associated with heterozygosity. For linkage group formation, HetMappS includes both a reference-guided synteny pipeline and a reference-independent de novo pipeline. The de novo pipeline can be utilized for under-characterized or high diversity families that lack an appropriate reference. We applied both HetMappS pipelines in five half-sib F1 families involving genetically diverse Vitis spp. Starting with at least 116,466 putative SNPs per family, the HetMappS pipelines identified 10,440 to 17,267 phased pseudo-testcross (Pt) markers and generated high-confidence maps. Pt marker density exceeded crossover resolution in all cases; up to 5,560 non-redundant markers were used to generate parental maps ranging from 1,047 cM to 1,696 cM. The number of markers used was strongly correlated with family size in both de novo and synteny maps (r = 0.92 and 0.91, respectively). Comparisons between allele and tag frequencies suggested that many markers were in tandem repeats and mapped as single loci, while markers in regions of more than two repeats were removed during map curation. Both pipelines generated similar genetic maps, and genetic order was strongly correlated with the reference genome physical order in all cases. Independently created genetic maps from shared parents exhibited nearly identical results. Flower sex was mapped in three families and correctly localized to the known sex locus in all cases. The HetMappS pipeline could have wide application for genetic mapping in highly heterozygous species, and its modularity provides opportunities to adapt portions of the pipeline to other family types, genotyping technologies or applications. PMID:26244767

Modified combination of platelet count and neutrophil "to" lymphocyte ratio as a prognostic factor in patients with advanced head and neck cancer.

PubMed

Nakayama, Masahiro; Gosho, Masahiko; Hirose, Yuki; Nishimura, Bungo; Tanaka, Shuho; Tabuchi, Keiji; Okubo, Hideki; Wada, Tetsuro; Hara, Akira

2018-06-01

We evaluated the prognostic potential of the combination of platelet count and neutrophil to lymphocyte ratio (COP-NLR) in patients with advanced head and neck cancer. We proposed a modified COP-NLR scoring system defined as follows: score 0 (platelet count level <300 × 10 9 /L and NLR <3); score 1 (platelet count level ≥300 × 10 9 /L and NLR <3); and score 2 (NLR ≥3). We assessed whether the modified scoring system had better performance as an indicator of prognosis than the existing COP-NLR scoring system (original and 4-group scores). A total of 248 patients were enrolled. The Akaike Information Criterion value with the modified COP-NLR score was the smallest among the 3 models. The 3-year survival rates according to the modified COP-NLR scores of 0, 1, and 2 were 80.6%, 59.9%, and 23.8%, respectively. The modified COP-NLR score is a useful prognostic marker in patients with advanced head and neck cancer. © 2018 Wiley Periodicals, Inc.

Ankle brachial index, MRI markers and cognition: The Epidemiology of Dementia in Singapore study.

PubMed

Shaik, Muhammad Amin; Venketasubramanian, Narayanaswamy; Cheng, Ching-Yu; Wong, Tien Yin; Vrooman, Henri; Ikram, Mohammad Kamran; Hilal, Saima; Chen, Christopher

2017-08-01

Previous studies showed an independent association of low ankle-brachial index (ABI) with cognitive impairment. However, the association between low ABI and cognition in the presence of both cerebrovascular disease (CeVD) and neurodegeneration is lacking. We aimed at investigating a) the association of low ABI with markers of CeVD and cortical thickness, and b) whether the association of low ABI with cognition is influenced by these markers. Data was drawn from the Epidemiology of Dementia In Singapore (EDIS) study where all participants (n = 832) underwent neuropsychological tests and 3T brain magnetic resonance imaging (MRI) to assess CeVD markers as well as cortical thicknesses. Cognitive function was expressed as a global composite z-score and domain-specific z-scores of a comprehensive neuropsychological battery. Multivariate analyses showed low ABI to be independently associated with intracranial stenosis [odds ratios (OR): 1.51; 95% confidence interval (CI):1.23-1.87] and lacunar infarcts [OR: 1.29; 95% CI: 1.06-1.57]. A low ABI was also independently associated with smaller cortical thickness globally [β: 0.09; 95% CI: 0.27-0.16] as well as with the limbic [β: 0.10; 95% CI: 0.03-0.17], temporal [β: 0.09; 95% CI: 0.02-0.15], parietal [β: 0.08; 95% CI: 0.02-0.15], and occipital [β: 0.09; 95% CI: 0.03-0.16] lobes. Low ABI was associated with worse performance in verbal memory [β: 0.06; 95% CI: 0.01-0.12], which became attenuated in the presence of MRI markers. A low ABI is associated with MRI markers, and affects cognition in the presence of CeVD and neurodegeneration. Atherosclerosis should be targeted as a potentially modifiable risk factor to prevent cognitive disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

Utility of combinations of biomarkers, cognitive markers, and risk factors to predict conversion from mild cognitive impairment to Alzheimer disease in patients in the Alzheimer's disease neuroimaging initiative.

PubMed

Gomar, Jesus J; Bobes-Bascaran, Maria T; Conejero-Goldberg, Concepcion; Davies, Peter; Goldberg, Terry E

2011-09-01

Biomarkers have become increasingly important in understanding neurodegenerative processes associated with Alzheimer disease. Markers include regional brain volumes, cerebrospinal fluid measures of pathological Aβ1-42 and total tau, cognitive measures, and individual risk factors. To determine the discriminative utility of different classes of biomarkers and cognitive markers by examining their ability to predict a change in diagnostic status from mild cognitive impairment to Alzheimer disease. Longitudinal study. We analyzed the Alzheimer's Disease Neuroimaging Initiative database to study patients with mild cognitive impairment who converted to Alzheimer disease (n = 116) and those who did not convert (n = 204) within a 2-year period. We determined the predictive utility of 25 variables from all classes of markers, biomarkers, and risk factors in a series of logistic regression models and effect size analyses. The Alzheimer's Disease Neuroimaging Initiative public database. Primary outcome measures were odds ratios, pseudo- R(2)s, and effect sizes. In comprehensive stepwise logistic regression models that thus included variables from all classes of markers, the following baseline variables predicted conversion within a 2-year period: 2 measures of delayed verbal memory and middle temporal lobe cortical thickness. In an effect size analysis that examined rates of decline, change scores for biomarkers were modest for 2 years, but a change in an everyday functional activities measure (Functional Assessment Questionnaire) was considerably larger. Decline in scores on the Functional Assessment Questionnaire and Trail Making Test, part B, accounted for approximately 50% of the predictive variance in conversion from mild cognitive impairment to Alzheimer disease. Cognitive markers at baseline were more robust predictors of conversion than most biomarkers. Longitudinal analyses suggested that conversion appeared to be driven less by changes in the neurobiologic trajectory of the disease than by a sharp decline in functional ability and, to a lesser extent, by declines in executive function.

hSAGEing: an improved SAGE-based software for identification of human tissue-specific or common tumor markers and suppressors.

PubMed

Yang, Cheng-Hong; Chuang, Li-Yeh; Shih, Tsung-Mu; Chang, Hsueh-Wei

2010-12-17

SAGE (serial analysis of gene expression) is a powerful method of analyzing gene expression for the entire transcriptome. There are currently many well-developed SAGE tools. However, the cross-comparison of different tissues is seldom addressed, thus limiting the identification of common- and tissue-specific tumor markers. To improve the SAGE mining methods, we propose a novel function for cross-tissue comparison of SAGE data by combining the mathematical set theory and logic with a unique "multi-pool method" that analyzes multiple pools of pair-wise case controls individually. When all the settings are in "inclusion", the common SAGE tag sequences are mined. When one tissue type is in "inclusion" and the other types of tissues are not in "inclusion", the selected tissue-specific SAGE tag sequences are generated. They are displayed in tags-per-million (TPM) and fold values, as well as visually displayed in four kinds of scales in a color gradient pattern. In the fold visualization display, the top scores of the SAGE tag sequences are provided, along with cluster plots. A user-defined matrix file is designed for cross-tissue comparison by selecting libraries from publically available databases or user-defined libraries. The hSAGEing tool provides a combination of friendly cross-tissue analysis and an interface for comparing SAGE libraries for the first time. Some up- or down-regulated genes with tissue-specific or common tumor markers and suppressors are identified computationally. The tool is useful and convenient for in silico cancer transcriptomic studies and is freely available at http://bio.kuas.edu.tw/hSAGEing.

The relationship between subjective appetite sensations, markers of inflammation and appetite in dialysis patients.

PubMed

Zabel, R; Ash, S; King, N; Bauer, J

2009-08-01

Poor appetite is a marker of morbidity and mortality in haemodialysis patients, making it an important area for research. Visual analogue scales (VAS) can capture a range of subjective sensations related to appetite (such as hunger, desire to eat or fullness), but have not been commonly used to measure appetite in dialysis patients. The present study aimed to explore the association between retrospective ratings of appetite using VAS and a range of clinical variables, as well as biomarkers of appetite in haemodialysis patients. Twenty-eight haemodialysis patients [mean age 61 +/- 17 years, 50% male, median dialysis vintage 19.5 (4-101) months] rated their appetite using VAS for hunger, fullness and desire to eat and a five-point categorical scale measuring general appetite. Blood levels of the appetite peptides leptin, ghrelin and peptide YY were also measured. Hunger ratings measured by VAS were significantly (P < 0.05) correlated with a range of clinical, nutritional and inflammatory markers: age (r = -0.376), co-morbidities, (r = -0.380) Patient-Generated Subjective Global Assessment score (r = -0.451), weight (r = -0.375), fat-free mass (r = -0.435), C-reactive protein (r = -0.383) and intercellular adhesion molecule (r = -0.387). There was a consistent relationship between VAS and appetite on a five-point categorical scale for questions of hunger, and a similar trend for desire to eat, but not for fullness. Neither method for measuring subjective appetite correlated with appetite peptides. Retrospective ratings of hunger on a VAS are associated with a range of clinical variables and further studies are warranted to support their use as a method for measuring appetite in dialysis patients.

Characterization of 32 microsatellite loci for the Pacific red snapper, Lutjanus peru, through next generation sequencing.

PubMed

Paz-García, David A; Munguía-Vega, Adrián; Plomozo-Lugo, Tomas; Weaver, Amy Hudson

2017-04-01

We developed a set of hypervariable microsatellite markers for the Pacific red snapper (Lutjanus peru), an economically important marine fish for small-scale fisheries in the west coast of Mexico. We performed shotgun genome sequencing with the 454 XL titanium chemistry and used bioinformatic tools to search for perfect microsatellite loci. We selected 66 primer pairs that were synthesized and genotyped in an ABI PRISM 3730XL DNA sequencer in 32 individuals from the Gulf of California. We estimated levels of genetic diversity, deviations from linkage and Hardy-Weinberg equilibrium, estimated the frequency of null alleles and the probability of individual identity for the new markers. We reanalyzed 16 loci in 16 individuals to estimate genotyping error rates. Eighteen loci failed to amplify, 16 loci were discarded due to unspecific amplifications and 32 loci (14 tetranucleotide and 18 dinucleotide) were successfully scored. The average number of alleles per locus was 21 (±6.87, SD) and ranged from 8 to 34. The average observed and expected heterozygosities were 0.787 (±0.144 SD, range 0.250-0.935) and 0.909 (±0.122 SD, range 0.381-0.965), respectively. No significant linkage was detected. Eight loci showed deviations from Hardy-Weinberg equilibrium, and from these, four loci showed moderate null allele frequencies (0.104-0.220). The probability of individual identity for the new loci was 1.46 -62 . Genotyping error rates averaged 9.58%. The new markers will be useful to investigate patterns of larval dispersal, metapopulation dynamics, fine-scale genetic structure and diversity aimed to inform the implementation of spatially explicit fisheries management strategies in the Gulf of California.

X-linked cardiomyopathy is heterogeneous

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

Wilson, M.J.; Sillence, D.O.; Mulley, J.C.

Two major loci of X-linked cardiomyopathy have been mapped by linkage analysis. The gene for X-linked dilated cardiomyopathy (XLCM) is mapped to the dystrophin locus at Xp21, while Barth syndrome has been localised to distal Xq28. XLCM usually presents in juvenile males with no skeletal disease but decreased dystrophin in cardiac muscle. Barth syndrome most often presents in infants and is characterized by skeletal myopathy, short stature and neutropenia in association with cardiomyopathy of variable severity. Prior to carrier or prenatal diagnosis in a family, delineation of the cardiomyopathy locus involved is essential. We report the linkage mapping of amore » large kindred in which several male infants have died with hypertrophic cardiomyopathy. There is a family history of unexplained death of infant males less than 6 months old over 4 generations. Features of Barth syndrome such as short stature, skeletal myopathy and neutropenia have not been observed. Genotyping at 10 marker loci in Xq28 has revealed significant pairwise lod scores with the cardiomyopathy phenotype at DXS52 (Z=2.21 at {theta}=0.0), at markers p26 and p39 near DXS15 (Z=2.30 at {theta}=0.0) and at F8C (Z=2.24 at {theta}=0.0). A recombinant detected with DXS296 defines the proximal limit to the localization. No recombinants were detected at any of the loci distal to DXS296. The most distal marker in Xq28, DXS1108, is within 500 kb of the telomere. As the gene in this family is localized to Xq28, it is possible that this disorder is an allelic variant at the Barth syndrome locus.« less

Mode of delivery has an independent impact on neonatal condition at birth.

PubMed

Prior, Tomas; Kumar, Sailesh

2014-10-01

Current intra-partum monitoring techniques are often criticized for their poor specificity, with their performance frequently evaluated using measures of the neonatal condition at birth as a surrogate marker for intra-partum fetal compromise. However, these measures may potentially be influenced by a multitude of other factors, including the mode of delivery itself. This study aimed to investigate the impact of mode of delivery on neonatal condition at birth. This prospective observational study, undertaken at a tertiary referral maternity unit in London, UK, included 604 'low risk' women recruited prior to delivery. Commonly assessed neonatal outcome variables (Apgar score at 1 and 5min, umbilical artery pH and base excess, neonatal unit admission, and a composite neonatal outcome score) were used to compare the condition at birth between babies born by different modes of delivery, using one-way ANOVA and chi-squared testing. Infants born by instrumental delivery for presumed fetal compromise had the poorest condition at birth (mean composite score=1.20), whereas those born by Cesarean section for presumed fetal compromise had a better condition at birth (mean composite score=0.64) (p=<0.001). No difference in composite neonatal outcome scores was observed between babies born by instrumental delivery for a prolonged second stage (no evidence of compromise), and those born by Cesarean delivery for presumed fetal compromise. Mode of delivery represents a potential confounding factor when using condition at birth as a surrogate marker of intra-partum fetal compromise. When evaluating the efficacy of intra-partum monitoring techniques, the isolated use of Apgar scores, umbilical artery acidosis and neonatal unit admission should be discouraged. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Common susceptibility alleles and SQSTM1 mutations predict disease extent and severity in a multinational study of patients with Paget's disease.

PubMed

Albagha, Omar M E; Visconti, Micaela Rios; Alonso, Nerea; Wani, Sachin; Goodman, Kirsteen; Fraser, William D; Gennari, Luigi; Merlotti, Daniela; Gianfrancesco, Fernando; Esposito, Teresa; Rendina, Domenico; di Stefano, Marco; Isaia, Giancarlo; Brandi, Maria Luisa; Giusti, Francesca; Del Pino-Montes, Javier; Corral-Gudino, Luis; Gonzalez-Sarmiento, Rogelio; Ward, Lynley; Rea, Sarah L; Ratajczak, Thomas; Walsh, John P; Ralston, Stuart H

2013-11-01

Paget's disease of bone (PDB) has a strong genetic component. Here, we investigated possible associations between genetic variants that predispose to PDB and disease severity. Allelic variants identified as predictors of PDB from genome-wide association studies were analyzed in 1940 PDB patients from the United Kingdom, Italy, Western Australia, and Spain. A cumulative risk allele score was constructed by adding the variants together and relating this to markers of disease severity, alone and in combination with SQSTM1 mutations. In SQSTM1-negative patients, risk allele scores in the highest tertile were associated with a 27% increase in disease extent compared with the lowest tertile (p < 0.00001) with intermediate values in the middle tertile (20% increase; p = 0.0007). The effects were similar for disease severity score, which was 15% (p = 0.01) and 25% (p < 0.00001) higher in the middle and upper tertiles, respectively. Risk allele score remained a significant predictor of extent and severity when SQSTM-positive individuals were included, with an effect size approximately one-third of that observed with SQSTM1 mutations. A genetic risk score was developed by combining information from both markers, which identified subgroups of individuals with low, medium, and high levels of severity with a specificity of 70% and sensitivity of 55%. Risk allele scores and SQSTM1 mutations both predict extent and severity of PDB. It is possible that with further refinement, genetic profiling may be of clinical value in identifying individuals at high risk of severe disease who might benefit from enhanced surveillance and early intervention. © 2013 American Society for Bone and Mineral Research.

Factors predicting labor induction success: a critical analysis.

PubMed

Crane, Joan M G

2006-09-01

Because of the risk of failed induction of labor, a variety of maternal and fetal factors as well as screening tests have been suggested to predict labor induction success. Certain characteristics of the woman (including parity, age, weight, height and body mass index), and of the fetus (including birth weight and gestational age) are associated with the success of labor induction; with parous, young women who are taller and lower weight having a higher rate of induction success. Fetuses with a lower birth weight or increased gestational age are also associated with increased induction success. The condition of the cervix at the start of induction is an important predictor, with the modified Bishop score being a widely used scoring system. The most important element of the Bishop score is dilatation. Other predictors, including transvaginal ultrasound (TVUS) and biochemical markers [including fetal fibronectin (fFN)] have been suggested. Meta-analyses of studies identified from MEDLINE, PubMed, and EMBASE and published from 1990 to October 2005 were performed evaluating the use of TVUS and fFN in predicting labor induction success in women at term with singleton gestations. Both TVUS and Bishop score predicted successful induction [likelihood ratio (LR)=1.82, 95% confidence interval (CI)=1.51-2.20 and LR=2.10, 95%CI=1.67-2.64, respectively]. As well, fFN and Bishop score predicted successful induction (LR=1.49, 95%CI=1.20-1.85, and LR=2.62, 95%CI=1.88-3.64, respectively). Although TVUS and fFN predicted successful labor induction, neither has been shown to be superior to Bishop score. Further research is needed to evaluate these potential predictors and insulin-like growth factor binding protein-1 (IGFBP-1), another potential biochemical marker.

Posture-cognitive dual-tasking: A relevant marker of depression-related psychomotor retardation. An illustration of the positive impact of repetitive transcranial magnetic stimulation in patients with major depressive disorder.

PubMed

Deschamps, Thibault; Sauvaget, Anne; Pichot, Anne; Valrivière, Pierre; Maroulidès, Maxime; Bois, Aurore; Bulteau, Samuel; Thomas-Ollivier, Véronique

2016-12-01

This study examined whether postural control variables, particularly the center-of-pressure (COP) velocity-based parameters, could be a relevant hallmark of depression-related psychomotor retardation (PMR). We first aimed at investigating the interplay between the PMR scores and the COP performance in patients with major depressive disorder (MDD), as compared to age-matched healthy controls; secondly, we focused on the impact of a repetitive transcranial magnetic stimulation (rTMS) treatment on depression, PMR scores and postural performance. 16 MDD patients, and a control group of 16 healthy adults, were asked to maintain quiet standing balance during two trials with or without vision, and while backward counting (dual task). All the position and velocity-based COP variables were computed. Before and after the rTMS session (n eligible MDD = 10), we assessed the depression level with the Montgomery-Asberg Depression Rating Scale (MADRS), the PMR scores with the French Retardation Rating Scale for Depression (ERD), and postural performance. Before the treatment, significant positive partial correlations were found between the pre-ERD scores and the velocity-based COP variables, especially in the dual-task conditions (p < 0.05). In contrast, there was no significant correlation between the post-ERD scores and any postural parameter after the treatment. The MADRS and ERD scores showed a significant decrease between before and after the rTMS intervention. For the first time, the findings clearly validated the view that the assessment of postural performance - easy to envisage in clinical settings-constitutes a reliable and objective marker of PMR in MDD patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Risk assessment using a novel score to predict anastomotic leak and major complications after oesophageal resection.

PubMed

Noble, Fergus; Curtis, Nathan; Harris, Scott; Kelly, Jamie J; Bailey, Ian S; Byrne, James P; Underwood, Timothy J

2012-06-01

Oesophagectomy is associated with significant morbidity and mortality. A simple score to define a patient's risk of developing major complications would be beneficial. Patients who underwent upper gastrointestinal resections with an oesophageal anastomosis between 2005 and 2010 were reviewed and formed the development dataset with resections performed in 2011 forming a prospective validation dataset. The association between post-operative C-reactive protein (CRP), white cell count (WCC) and albumin levels with anastomotic leak (AL) or major complication including death using the Clavien-Dindo (CD) classification were analysed by receiver operating characteristic curves. After multivariate analysis, from the development dataset, these factors were combined to create a novel score which was subsequently tested on the validation dataset. Two hundred fifty-eight patients were assessed to develop the score. Sixty-three patients (25%) developed a major complication, and there were seven (2.7%) in-patient deaths. Twenty-six (10%) patients were diagnosed with AL at median post-operative day 7 (range: 5-15). CRP (p = 0.002), WCC (p < 0.0001) and albumin (p = 0.001) were predictors of AL. Combining these markers improved prediction of AL (NUn score > 10: sensitivity 95%, specificity 49%, diagnostic accuracy 0.801 (95% confidence interval: 0.692-0.909, p < 0.0001)). The validation dataset confirmed these findings (NUn score > 10: sensitivity 100%, specificity 57%, diagnostic accuracy 0.879 (95% CI 0.763-0.994, p = 0.014)) and a major complication or death (NUn > 10: sensitivity 89%, specificity 63%, diagnostic accuracy 0.856 (95% CI 0.709-1, p = 0.001)). Blood-borne markers of the systemic inflammatory response are predictors of AL and major complications after oesophageal resection. When combined they may categorise a patient's risk of developing a serious complication with higher sensitivity and specificity.

Plasma suPAR as a prognostic biological marker for ICU mortality in ARDS patients.

PubMed

Geboers, Diederik G P J; de Beer, Friso M; Tuip-de Boer, Anita M; van der Poll, Tom; Horn, Janneke; Cremer, Olaf L; Bonten, Marc J M; Ong, David S Y; Schultz, Marcus J; Bos, Lieuwe D J

2015-07-01

We investigated the prognostic value of plasma soluble urokinase plasminogen activator receptor (suPAR) on day 1 in patients with the acute respiratory distress syndrome (ARDS) for intensive care unit (ICU) mortality and compared it with established disease severity scores on day 1. suPAR was determined batchwise in plasma obtained within 24 h after admission. 632 ARDS patients were included. Significantly (P = 0.02) higher median levels of suPAR were found with increasing severity of ARDS: 5.9 ng/ml [IQR 3.1-12.8] in mild ARDS (n = 82), 8.4 ng/ml [IQR 4.1-15.0] in moderate ARDS (n = 333), and 9.0 ng/ml [IQR 4.5-16.0] in severe ARDS (n = 217). Non-survivors had higher median levels of suPAR [12.5 ng/ml (IQR 5.1-19.5) vs. 7.4 ng/ml (3.9-13.6), P < 0.001]. The area under the receiver operator characteristic curve (ROC-AUC) for mortality of suPAR (0.62) was lower than the ROC-AUC of the APACHE IV score (0.72, P = 0.007), higher than that of the ARDS definition classification (0.53, P = 0.005), and did not differ from that of the SOFA score (0.68, P = 0.07) and the oxygenation index (OI) (0.58, P = 0.29). Plasma suPAR did not improve the discrimination of the established disease severity scores, but did improve net reclassification of the APACHE score (29%), SOFA score (23%), OI (38%), and Berlin definition classification (39%). As a single biological marker, the prognostic value for death of plasma suPAR in ARDS patients is low. Plasma suPAR, however, improves the net reclassification, suggesting a potential role for suPAR in ICU mortality prediction models.

Efficiency of the Use of Pedigree and Molecular Marker Information in Conservation Programs

PubMed Central

Fernández, Jesús; Villanueva, Beatriz; Pong-Wong, Ricardo; Toro, Miguel Ángel

2005-01-01

The value of molecular markers and pedigree records, separately or in combination, to assist in the management of conserved populations has been tested. The general strategy for managing the population was to optimize contributions of parents to the next generation for minimizing the global weighted coancestry. Strategies differed in the type of information used to compute global coancestries, the number and type of evaluated individuals, and the system of mating. Genealogical information proved to be very useful (at least for 10 generations of management) to arrange individuals' contributions via the minimization of global coancestry. In fact, the level of expected heterozygosity after 10 generations yielded by this strategy was 88–100% of the maximum possible improvement obtained if the genotype for all loci was known. Marker information was of very limited value if used alone. The amount and degree of polymorphism of markers to be used to compute molecular coancestry had to be high to mimic the performance of the strategy relying on pedigree, especially in the short term (for example, >10 markers per chromosome with 10 alleles each were needed if only the parents' genotype was available). When both sources of information are combined to calculate the coancestry conditional on markers, clear increases in effective population size (Ne) were found, but observed diversity levels (either gene or allelic diversity) in the early generations were quite similar to the ones obtained with pedigree alone. The advantage of including molecular information is greater when information is available on a greater number of individuals (offspring and parents vs. parents only). However, for realistic situations (i.e., large genomes) the benefits of using information on offspring are small. The same conclusions were reached when comparing the use of the different types of information (genealogical or/and molecular) to perform minimum coancestry matings. PMID:15879510

Identification of cancer stem cell markers in human malignant mesothelioma cells

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

Ghani, Farhana Ishrat; Yamazaki, Hiroto; Iwata, Satoshi

2011-01-14

Research highlights: {yields} We performed serial transplantation of surgical samples and established new cell lines of malignant mesothelioma. {yields} SP cell and expressions of CD9/CD24/CD26 were often observed in mesothelioma cell lines. {yields} SP and CD24{sup +} cells proliferated by asymmetric cell division-like manner. CD9{sup +} and CD24{sup +} cells have higher potential to generate spheroid colony. {yields} The marker-positive cells have clear tendency to generate larger tumors in mice. -- Abstract: Malignant mesothelioma (MM) is an aggressive and therapy-resistant neoplasm arising from the pleural mesothelial cells and usually associated with long-term asbestos exposure. Recent studies suggest that tumors containmore » cancer stem cells (CSCs) and their stem cell characteristics are thought to confer therapy-resistance. However, whether MM cell has any stem cell characteristics is not known. To understand the molecular basis of MM, we first performed serial transplantation of surgical samples into NOD/SCID mice and established new cell lines. Next, we performed marker analysis of the MM cell lines and found that many of them contain SP cells and expressed several putative CSC markers such as CD9, CD24, and CD26. Interestingly, expression of CD26 closely correlated with that of CD24 in some cases. Sorting and culture assay revealed that SP and CD24{sup +} cells proliferated by asymmetric cell division-like manner. In addition, CD9{sup +} and CD24{sup +} cells have higher potential to generate spheroid colony than negative cells in the stem cell medium. Moreover, these marker-positive cells have clear tendency to generate larger tumors in mouse transplantation assay. Taken together, our data suggest that SP, CD9, CD24, and CD26 are CSC markers of MM and could be used as novel therapeutic targets.« less

Increased Expression of ALDH1A1 in Prostate Cancer is Correlated With Tumor Aggressiveness: A Tissue Microarray Study of Iranian Patients.

PubMed

Kalantari, Elham; Saadi, Faezeh H; Asgari, Mojgan; Shariftabrizi, Ahmad; Roudi, Raheleh; Madjd, Zahra

2017-09-01

Subpopulations of prostate cancer (PCa) cells expressing putative stem cell markers possess the ability to promote tumor growth, maintenance, and progression. This study aimed to evaluate the expression patterns and clinical significance of putative stem cell marker aldehyde dehydrogenase 1 A1 (ALDH1A1) in prostate tumor tissues. ALDH1A1 expression was examined in a well-defined series of prostate tissues, including 105 (68%) samples of PCa, 21 (13%) samples of high-grade prostatic intraepithelial neoplasia, and 31 (19%) samples of benign prostate hyperplasia, which were embedded in tissue microarray blocks. The correlation of ALDH1A1 expression with clinicopathologic parameters was also assessed. There was a significant difference between the expression level of ALDH1A1 in PCa compared with the high-grade prostatic intraepithelial neoplasia and benign prostate hyperplasia samples (P<0.001). PCa cells expressing ALDH1A1 were more often seen in samples with advanced Gleason score (P=0.05) and high serum prostate specific antigen level (P=0.02). In addition, a positive correlation was found between ALDH1A1 expression and primary tumor stage and regional lymph node involvement (P=0.04 and 0.03, respectively). The significant association between ALDH1A1 expressions with Gleason score indicates the potential role of this protein in PCa tumorigenesis and aggressive behavior; therefore, this cancer stem cell marker can be used as a promising candidate for targeted therapy of PCa, especially those with high Gleason score.

Multi-parametric spinal cord MRI as potential progression marker in amyotrophic lateral sclerosis.

PubMed

El Mendili, Mohamed-Mounir; Cohen-Adad, Julien; Pelegrini-Issac, Mélanie; Rossignol, Serge; Morizot-Koutlidis, Régine; Marchand-Pauvert, Véronique; Iglesias, Caroline; Sangari, Sina; Katz, Rose; Lehericy, Stéphane; Benali, Habib; Pradat, Pierre-François

2014-01-01

To evaluate multimodal MRI of the spinal cord in predicting disease progression and one-year clinical status in amyotrophic lateral sclerosis (ALS) patients. After a first MRI (MRI1), 29 ALS patients were clinically followed during 12 months; 14/29 patients underwent a second MRI (MRI2) at 11±3 months. Cross-sectional area (CSA) that has been shown to be a marker of lower motor neuron degeneration was measured in cervical and upper thoracic spinal cord from T2-weighted images. Fractional anisotropy (FA), axial/radial/mean diffusivities (λ⊥, λ//, MD) and magnetization transfer ratio (MTR) were measured within the lateral corticospinal tract in the cervical region. Imaging metrics were compared with clinical scales: Revised ALS Functional Rating Scale (ALSFRS-R) and manual muscle testing (MMT) score. At MRI1, CSA correlated significantly (P<0.05) with MMT and arm ALSFRS-R scores. FA correlated significantly with leg ALFSRS-R scores. One year after MRI1, CSA predicted (P<0.01) arm ALSFSR-R subscore and FA predicted (P<0.01) leg ALSFRS-R subscore. From MRI1 to MRI2, significant changes (P<0.01) were detected for CSA and MTR. CSA rate of change (i.e. atrophy) highly correlated (P<0.01) with arm ALSFRS-R and arm MMT subscores rate of change. Atrophy and DTI metrics predicted ALS disease progression. Cord atrophy was a better biomarker of disease progression than diffusion and MTR. Our study suggests that multimodal MRI could provide surrogate markers of ALS that may help monitoring the effect of disease-modifying drugs.

Low Cognitive Awareness, but Not Complaint, is a Good Marker of Preclinical Alzheimer's Disease.

PubMed

Cacciamani, Federica; Tandetnik, Caroline; Gagliardi, Geoffroy; Bertin, Hugo; Habert, Marie-Odile; Hampel, Harald; Boukadida, Laurie; Révillon, Marie; Epelbaum, Stéphane; Dubois, Bruno

2017-01-01

Subjective cognitive decline (SCD) may result from many conditions, including Alzheimer's disease (AD). In this study, we searched for a specific pattern of SCD in asymptomatic individuals at risk for AD. Cognitively normal older adults (N = 318) reporting SCD and their informants were enrolled in the INSIGHT-PreAD cohort. We examined the relationship between six SCD measures and both cognitive scores and AD neuroimaging markers (amyloid burden, hippocampal atrophy and brain hypometabolism). An awareness of cognitive decline index (ACDI) has been introduced based on the subject-informant discrepancy in a questionnaire of SCD and participants with low versus high awareness were compared. Scores in the INSIGHT-PreAD SCD questionnaires did not correlate with AD neuroimaging markers. As well, no correlation has been found between SCD measures and cognitive scores. Comparing subjects with a low (n = 19) and high (n = 86) level of awareness, no significant difference in terms of demography, neuropsychiatric symptoms, autonomy, quality of life, cognition, and hippocampal volume was found. However, the "low awareness" group showed greater amyloid burden and lower cortical metabolism, compared to the "high awareness" group. This study provided additional evidence that reporting SCD by itself is not a specific symptom of preclinical AD. Conversely, a low cognitive awareness (namely, when subjects report fewer difficulties than their relatives do) may represent a very early form of anosognosia and serve as a specific indicator of preclinical AD. This finding is of key importance as an enrichment factor to consider in both clinical practice and research trials.

Thyrotropin serum levels are differentially associated with biochemical markers of bone turnover and stiffness in women and men: results from the SHIP cohorts.

PubMed

Tsourdi, E; Wallaschofski, H; Rauner, M; Nauck, M; Pietzner, M; Rettig, R; Ittermann, T; Völzke, H; Völker, U; Hofbauer, L C; Hannemann, A

2016-02-01

In two large German population-based cohorts, we showed positive associations between serum thyrotropin (TSH) concentrations and the Fracture Risk Assessment score (FRAX) in men and positive associations between TSH concentrations and bone turnover markers in women. The role of thyroid hormones on bone stiffness and turnover is poorly defined. Existing studies are confounded by differences in design and small sample size. We assessed the association between TSH serum concentrations and bone stiffness and turnover in the SHIP cohorts, which are two population-based cohorts from a region in Northern Germany comprising 2654 men and women and 3261 men and women, respectively. We calculated the bone stiffness index using quantitative ultrasound (QUS) at the calcaneus, employed FRAX score for assessment of major osteoporotic fractures, and measured bone turnover markers, N-terminal propeptide of type I procollagen (P1NP), bone-specific alkaline phosphatase (BAP), osteocalcin, and type I collagen cross-linked C-telopeptide (CTX) in all subjects and sclerostin in a representative subgroup. There was no association between TSH concentrations and the stiffness index in both genders. In men, TSH correlated positively with the FRAX score both over the whole TSH range (p < 0.01) and within the reference TSH range (p < 0.01). There were positive associations between TSH concentrations and P1NP, BAP, osteocalcin, and CTX (p < 0.01) in women but not in men. There was no significant association between TSH and sclerostin levels. TSH serum concentrations are associated with gender-specific changes in bone turnover and stiffness.

What role for the home learning environment and parenting in reducing the socioeconomic gradient in child development? Findings from the Millennium Cohort Study.

PubMed

Kelly, Y; Sacker, A; Del Bono, E; Francesconi, M; Marmot, M

2011-09-01

Early child health and development (ECD) is important for health in later life. Objectives were to (1) examine the extent of socioeconomic inequality in markers of ECD at ages 3 and 5 years; (2) examine whether the ECD-income gap widens between these ages; (3) assess the contribution of the home learning environment, family routines and psychosocial environment to observed inequalities in ECD. Data on socioemotional difficulties, and tests of cognitive ability in 3-year-old (n=15 382) and 5-year-old (n=15 042) children from the UK Millennium Cohort Study were used. Children in the highest income group were less likely to have socioemotional difficulties compared with those in the lowest income group at 3 and 5 years (2.4% vs 16.4% and 2.0% vs 15.9%, respectively) and had higher mean scores: age 3 'school readiness' 114 versus 99; verbal ability 54 versus 48, and age 5: verbal ability 60 versus 51, non-verbal ability 58 versus 54 and spatial ability 54 versus 48 (all p<0.001). The income gap in verbal ability scores widened between ages 3 and 5 (Wald test, p=0.04). Statistical adjustment for markers of home learning, family routines and psychosocial environments did more to explain the income gap in socioemotional difficulties than in cognitive test scores. Our results suggest that relationships between family income and markers of ECD are amenable to change. The role of home learning, family routines and psychosocial environmental factors are potentially important in closing income gaps in ECD.

Adherence to a healthy diet in relation to cardiovascular incidence and risk markers: evidence from the Caerphilly Prospective Study.

PubMed

Mertens, Elly; Markey, Oonagh; Geleijnse, Johanna M; Lovegrove, Julie A; Givens, D Ian

2018-04-01

Epidemiological findings indicate that higher adherence to a healthy diet may lower cardiovascular disease (CVD) risk. The present study aimed to investigate whether adherence to a healthy diet, assessed by the Healthy Diet Indicator (HDI), Dietary Approaches to Stop Hypertension (DASH) score, and Alternative Healthy Eating Index 2010 (AHEI-2010), was associated with CVD incidence and risk markers. Included in the present analyses were data from 1867 middle-aged men, aged 56.7 ± 4.5 years at baseline, recruited into the Caerphilly Prospective Study. Adherence to a healthy diet was examined in relation to CVD, coronary heart disease (CHD), and stroke incidence (Cox regression), and risk markers (linear regression) with adjustment for relevant confounders. The DASH score was inversely associated with CVD [hazard ratio (HR) 0.81; 95% confidence interval (CI) 0.66, 0.99], and stroke (HR 0.61; 95% CI 0.42, 0.88) incidence, but not with CHD after an average of 16.6 year follow-up, and with diastolic blood pressure, after 12 year follow-up. The AHEI-2010 was inversely associated with stroke (HR 0.66; 95% CI 0.42, 0.88) incidence, aortic pulse wave velocity, and C-reactive protein. The HDI was not associated with any single outcome. Higher DASH and AHEI-2010 scores were associated with lower CVD and stroke risk, and favourable cardiovascular health outcomes, suggesting that encouraging middle-aged men to comply with the dietary recommendations for a healthy diet may have important implications for future vascular disease and population health.

Application of ImmunoScore Model for the Differentiation between Active Tuberculosis and Latent Tuberculosis Infection as Well as Monitoring Anti-tuberculosis Therapy.

PubMed

Zhou, Yu; Du, Juan; Hou, Hong-Yan; Lu, Yan-Fang; Yu, Jing; Mao, Li-Yan; Wang, Feng; Sun, Zi-Yong

2017-01-01

Tuberculosis (TB) is a leading global public health problem. To achieve the end TB strategy, non-invasive markers for diagnosis and treatment monitoring of TB disease are urgently needed, especially in high-endemic countries such as China. Interferon-gamma release assays (IGRAs) and tuberculin skin test (TST), frequently used immunological methods for TB detection, are intrinsically unable to discriminate active tuberculosis (ATB) from latent tuberculosis infection (LTBI). Thus, the specificity of these methods in the diagnosis of ATB is dependent upon the local prevalence of LTBI. The pathogen-detecting methods such as acid-fast staining and culture, all have limitations in clinical application. ImmunoScore (IS) is a new promising prognostic tool which was commonly used in tumor. However, the importance of host immunity has also been demonstrated in TB pathogenesis, which implies the possibility of using IS model for ATB diagnosis and therapy monitoring. In the present study, we focused on the performance of IS model in the differentiation between ATB and LTBI and in treatment monitoring of TB disease. We have totally screened five immunological markers (four non-specific markers and one TB-specific marker) and successfully established IS model by using Lasso logistic regression analysis. As expected, the IS model can effectively distinguish ATB from LTBI (with a sensitivity of 95.7% and a specificity of 92.1%) and also has potential value in the treatment monitoring of TB disease.

Identification of three randomly amplified polymorphic DNA-polymerase chain reaction markers for distinguishing Asian and North American Gypsy Moths (Lepidoptera: Lymantriidae)

Treesearch

David E. Schreiber; Karen J. Garner; James M. Slavicek

1997-01-01

Gypsy moths originating in Asia have recently been introduced into North America, making it necessary to develop markers for distinguishing the Asian strain from the established North American population. We have identified 3 randomly amplified polymorphic DNA-polymerase chain reaction generated (RAPD-PCR) markers which are specific for either Asian or North American...

ReQON: a Bioconductor package for recalibrating quality scores from next-generation sequencing data

PubMed Central

2012-01-01

Background Next-generation sequencing technologies have become important tools for genome-wide studies. However, the quality scores that are assigned to each base have been shown to be inaccurate. If the quality scores are used in downstream analyses, these inaccuracies can have a significant impact on the results. Results Here we present ReQON, a tool that recalibrates the base quality scores from an input BAM file of aligned sequencing data using logistic regression. ReQON also generates diagnostic plots showing the effectiveness of the recalibration. We show that ReQON produces quality scores that are both more accurate, in the sense that they more closely correspond to the probability of a sequencing error, and do a better job of discriminating between sequencing errors and non-errors than the original quality scores. We also compare ReQON to other available recalibration tools and show that ReQON is less biased and performs favorably in terms of quality score accuracy. Conclusion ReQON is an open source software package, written in R and available through Bioconductor, for recalibrating base quality scores for next-generation sequencing data. ReQON produces a new BAM file with more accurate quality scores, which can improve the results of downstream analysis, and produces several diagnostic plots showing the effectiveness of the recalibration. PMID:22946927

Ultrafine particles generated from coloring with scented markers in the presence of ozone.

PubMed

Fung, C-C D; Shu, S; Zhu, Y

2014-10-01

High concentrations of ultrafine particles (UFPs) have been previously reported during school art activities. This is possibly due to secondary organic aerosols (SOAs) formed from reactions between ozone and volatile organic compounds emitted from art products. Four brands of markers, three scented and one unscented, were tested inside a stainless steel chamber at eight different ozone concentrations between 0 and 300 ppb. Out of the 32 tested markers, only the lemon- and orange-scented markers from one brand reacted with ozone to form UFPs. Limonene, pinene, and several other terpenes were identified as ingredients of ink in SOA-forming markers. Coloring with one lemon-scented marker for 1 min without ozone generated on average approximately 26 ± 4 ppb of limonene inside the chamber. At 150 ppb ozone, using one lemon marker for 1 min formed on average 7.7 × 10(10) particles. The particle size distribution indicated an initial mode of 15 nm which grew to 40 nm. At 50 ppb ozone and below, no significant SOA formation occurred. The number of particles formed is moderately correlated with the mass of ink used (R(2)  = 0.68). Based on these data, scented markers are not likely a strong source of SOA under normal indoor ozone levels. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Informative genomic microsatellite markers for efficient genotyping applications in sugarcane.

PubMed

Parida, Swarup K; Kalia, Sanjay K; Kaul, Sunita; Dalal, Vivek; Hemaprabha, G; Selvi, Athiappan; Pandit, Awadhesh; Singh, Archana; Gaikwad, Kishor; Sharma, Tilak R; Srivastava, Prem Shankar; Singh, Nagendra K; Mohapatra, Trilochan

2009-01-01

Genomic microsatellite markers are capable of revealing high degree of polymorphism. Sugarcane (Saccharum sp.), having a complex polyploid genome requires more number of such informative markers for various applications in genetics and breeding. With the objective of generating a large set of microsatellite markers designated as Sugarcane Enriched Genomic MicroSatellite (SEGMS), 6,318 clones from genomic libraries of two hybrid sugarcane cultivars enriched with 18 different microsatellite repeat-motifs were sequenced to generate 4.16 Mb high-quality sequences. Microsatellites were identified in 1,261 of the 5,742 non-redundant clones that accounted for 22% enrichment of the libraries. Retro-transposon association was observed for 23.1% of the identified microsatellites. The utility of the microsatellite containing genomic sequences were demonstrated by higher primer designing potential (90%) and PCR amplification efficiency (87.4%). A total of 1,315 markers including 567 class I microsatellite markers were designed and placed in the public domain for unrestricted use. The level of polymorphism detected by these markers among sugarcane species, genera, and varieties was 88.6%, while cross-transferability rate was 93.2% within Saccharum complex and 25% to cereals. Cloning and sequencing of size variant amplicons revealed that the variation in the number of repeat-units was the main source of SEGMS fragment length polymorphism. High level of polymorphism and wide range of genetic diversity (0.16-0.82 with an average of 0.44) assayed with the SEGMS markers suggested their usefulness in various genotyping applications in sugarcane.

A second generation SNP and SSR integrated linkage map and QTL mapping for the Chinese mitten crab Eriocheir sinensis

PubMed Central

Qiu, Gao-Feng; Xiong, Liang-Wei; Han, Zhi-Ke; Liu, Zhi-Qiang; Feng, Jian-Bin; Wu, Xu-Gan; Yan, Yin-Long; Shen, Hong; Huang, Long; Chen, Li

2017-01-01

The Chinese mitten crab Eriocheir sinensis is the most economically important cultivated crab species in China, and its genome has a high number of chromosomes (2n = 146). To obtain sufficient markers for construction of a dense genetic map for this species, we employed the recently developed specific-locus amplified fragment sequencing (SLAF-seq) method for large-scale SNPs screening and genotyping in a F1 full-sib family of 149 individuals. SLAF-seq generated 127,677 polymorphic SNP markers, of which 20,803 valid markers were assigned into five segregation types and were used together with previous SSR markers for linkage map construction. The final integrated genetic map included 17,680 SNP and 629 SSR markers on the 73 linkage groups (LG), and spanned 14,894.9 cM with an average marker interval of 0.81 cM. QTL mapping localized three significant growth-related QTL to a 1.2 cM region in LG53 as well as 146 sex-linked markers in LG48. Genome-wide QTL-association analysis further identified four growth-related QTL genes named LNX2, PAK2, FMRFamide and octopamine receptors. These genes are involved in a variety of different signaling pathways including cell proliferation and growth. The map and SNP markers described here will be a valuable resource for the E. sinensis genome project and selective breeding programs. PMID:28045132

Schizotypal thinking and associative processing: a response commonality analysis of verbal fluency.

PubMed Central

Duchêne, A; Graves, R E; Brugger, P

1998-01-01

OBJECTIVE: To determine whether people with high scores for schizotypal thinking generate more uncommon words in a letter fluency task than people with low scores. DESIGN: Prospective study. SETTING: University psychology department. PATIENTS: Forty healthy, right-handed students. INTERVENTIONS: Students were administered the Magical Ideation (MI) Scale and a 2-minute letter fluency task in which they named as many nouns as possible beginning with "A" or "F," in any order. OUTCOME MEASURES: Total number of words produced and percentage of unique, rare and common words (as determined by the responses of the whole group); scores on MI scale. RESULTS: Participants with high scores (above the median) on the MI scale generated as many words as those who had low scores. People in both groups also generated a comparable number of unique words (named by only 1 person) and common words (named by 6 or more people). As hypothesized, people with high scores on the MI scale generated more rare words (named by fewer than 6 people) than those with low scores. CONCLUSIONS: These findings support the view of a disinhibition of semantic network functioning as the neuropsychological basis of creative thought, magical ideation and thought disorder. PMID:9505061

Tracing Asian Seabass Individuals to Single Fish Farms Using Microsatellites

PubMed Central

Yue, Gen Hua; Xia, Jun Hong; Liu, Peng; Liu, Feng; Sun, Fei; Lin, Grace

2012-01-01

Traceability through physical labels is well established, but it is not highly reliable as physical labels can be easily changed or lost. Application of DNA markers to the traceability of food plays an increasingly important role for consumer protection and confidence building. In this study, we tested the efficiency of 16 polymorphic microsatellites and their combinations for tracing 368 fish to four populations where they originated. Using the maximum likelihood and Bayesian methods, three most efficient microsatellites were required to assign over 95% of fish to the correct populations. Selection of markers based on the assignment score estimated with the software WHICHLOCI was most effective in choosing markers for individual assignment, followed by the selection based on the allele number of individual markers. By combining rapid DNA extraction, and high-throughput genotyping of selected microsatellites, it is possible to conduct routine genetic traceability with high accuracy in Asian seabass. PMID:23285169

Directive and non-directive food-related parenting practices: Associations between an expanded conceptualization of food-related parenting practices and child dietary intake and weight outcomes.

PubMed

Loth, K A; Friend, S; Horning, M L; Neumark-Sztainer, D; Fulkerson, J A

2016-12-01

This study examines associations between an expanded conceptualization of food-related parenting practices, specifically, directive and non-directive control, and child weight (BMI z-score) and dietary outcomes [Healthy Eating Index (HEI) 2010, daily servings fruits/vegetables] within a sample of parent-child dyads (8-12 years old; n = 160). Baseline data from the Healthy Home Offerings via the Mealtime Environment (HOME Plus) randomized controlled trial was used to test associations between directive and non-directive control and child dietary outcomes and weight using multiple regression analyses adjusted for parental education. Overall variance explained by directive and non-directive control constructs was also calculated. Markers of directive control included pressure-to-eat and food restriction, assessed using subscales from the Child Feeding Questionnaire; markers of non-directive control were assessed with a parental role modeling scale and a home food availability inventory in which an obesogenic home food environment score was assigned based on the types and number of unhealthful foods available within the child's home food environment. Food restriction and pressure-to-eat were positively and negatively associated with BMI z-scores, respectively, but not with dietary outcomes. An obesogenic home food environment was inversely associated with both dietary outcomes; parental role modeling of healthful eating was positively associated with both dietary outcomes. Neither non-directive behavioral construct was significantly associated with BMI z-scores. Greater total variance in BMI-z was explained by directive control; greater total variance in dietary outcomes was explained by non-directive control. Including a construct of food-related parenting practices with separate markers for directive and non-directive control should be considered for future research. These concepts address different forms of parental control and, in the present study, yielded unique associations with child dietary and weight outcomes. Copyright © 2016 Elsevier Ltd. All rights reserved.

'Alzheimer's Progression Score': Development of a Biomarker Summary Outcome for AD Prevention Trials.

PubMed

Leoutsakos, J-M; Gross, A L; Jones, R N; Albert, M S; Breitner, J C S

2016-01-01

Alzheimer's disease (AD) prevention research requires methods for measurement of disease progression not yet revealed by symptoms. Preferably, such measurement should encompass multiple disease markers. Evaluate an item response theory (IRT) model-based latent variable Alzheimer Progression Score (APS) that uses multi-modal disease markers to estimate pre-clinical disease progression. Estimate APS scores in the BIOCARD observational study, and in the parallel PREVENT-AD Cohort and its sister INTREPAD placebo-controlled prevention trial. Use BIOCARD data to evaluate whether baseline and early APS trajectory predict later progression to MCI/dementia. Similarly, use longitudinal PREVENT-AD data to assess test measurement invariance over time. Further, assess portability of the PREVENT-AD IRT model to baseline INTREPAD data, and explore model changes when CSF markers are added or withdrawn. BIOCARD was established in 1995 and participants were followed up to 20 years in Baltimore, USA. The PREVENT-AD and INTREPAD trial cohorts were established between 2011-2015 in Montreal, Canada, using nearly identical entry criteria to enroll high-risk cognitively normal persons aged 60+ then followed for several years. 349 cognitively normal, primarily middle-aged participants in BIOCARD, 125 high-risk participants aged 60+ in PREVENT-AD, and 217 similar subjects in INTREPAD. 106 INTREPAD participants donated up to four serial CSF samples. Global cognitive assessment and multiple structural, functional, and diffusion MRI metrics, sensori-neural tests, and CSF concentrations of tau, Aβ42 and their ratio. Both baseline values and early slope of APS scores in BIOCARD predicted later progression to MCI or AD. Presence of CSF variables strongly improved such prediction. A similarly derived APS in PREVENT-AD showed measurement invariance over time and portability to the parallel INTREPAD sample. An IRT-based APS can summarize multimodal information to provide a longitudinal measure of pre-clinical AD progression, and holds promise as an outcome for AD prevention trials.

Influence of household rat infestation on leptospira transmission in the urban slum environment.

PubMed

Costa, Federico; Ribeiro, Guilherme S; Felzemburgh, Ridalva D M; Santos, Norlan; Reis, Renato Barbosa; Santos, Andreia C; Fraga, Deborah Bittencourt Mothe; Araujo, Wildo N; Santana, Carlos; Childs, James E; Reis, Mitermayer G; Ko, Albert I

2014-12-01

The Norway rat (Rattus norvegicus) is the principal reservoir for leptospirosis in many urban settings. Few studies have identified markers for rat infestation in slum environments while none have evaluated the association between household rat infestation and Leptospira infection in humans or the use of infestation markers as a predictive model to stratify risk for leptospirosis. We enrolled a cohort of 2,003 urban slum residents from Salvador, Brazil in 2004, and followed the cohort during four annual serosurveys to identify serologic evidence for Leptospira infection. In 2007, we performed rodent infestation and environmental surveys of 80 case households, in which resided at least one individual with Leptospira infection, and 109 control households. In the case-control study, signs of rodent infestation were identified in 78% and 42% of the households, respectively. Regression modeling identified the presence of R. norvegicus feces (OR, 4.95; 95% CI, 2.13-11.47), rodent burrows (2.80; 1.06-7.36), access to water (2.79; 1.28-6.09), and un-plastered walls (2.71; 1.21-6.04) as independent risk factors associated with Leptospira infection in a household. We developed a predictive model for infection, based on assigning scores to each of the rodent infestation risk factors. Receiver operating characteristic curve analysis found that the prediction score produced a good/excellent fit based on an area under the curve of 0.78 (0.71-0.84). Our study found that a high proportion of slum households were infested with R. norvegicus and that rat infestation was significantly associated with the risk of Leptospira infection, indicating that high level transmission occurs among slum households. We developed an easily applicable prediction score based on rat infestation markers, which identified households with highest infection risk. The use of the prediction score in community-based screening may therefore be an effective risk stratification strategy for targeting control measures in slum settings of high leptospirosis transmission.

Inflammatory markers as selection criteria of hepatocellular carcinoma in living-donor liver transplantation

PubMed Central

Na, Gun Hyung; Kim, Dong Goo; Han, Jae hyun; Kim, Eun Young; Lee, Soo Ho; Hong, Tae Ho; You, Young Kyoung

2014-01-01

AIM: To investigate that inflammatory markers can predict accurately the prognosis of hepatocelluar carcinoma (HCC) patients in living-donor liver transplantation (LDLT). METHODS: From October 2000 to November 2011, 224 patients who underwent living donor liver transplantation for HCC at our institution were enrolled in this study. We analyzed disease-free survival (DFS) and overall survival (OS) after LT in patients with HCC and designed a new score model using pretransplant neutrophil-lymphocyte ratio (NLR) and C-reactive protein (CRP). RESULTS: The DFS and OS in patients with an NLR level ≥ 6.0 or CRP level ≥ 1.0 were significantly worse than those of patients with an NLR level < 6.0 or CRP level < 1.0 (P = 0.049, P = 0.003 for NLR and P = 0.010, P < 0.001 for CRP, respectively). Using a new score model using the pretransplant NLR and CRP, we can differentiate HCC patients beyond the Milan criteria with a good prognosis from those with a poor prognosis. CONCLUSION: Combined with the Milan criteria, new score model using NLR and CRP represent new selection criteria for LDLT candidates with HCC, especially beyond the Milan criteria. PMID:24914382

Inflammatory markers as selection criteria of hepatocellular carcinoma in living-donor liver transplantation.

PubMed

Na, Gun Hyung; Kim, Dong Goo; Han, Jae Hyun; Kim, Eun Young; Lee, Soo Ho; Hong, Tae Ho; You, Young Kyoung

2014-06-07

To investigate that inflammatory markers can predict accurately the prognosis of hepatocelluar carcinoma (HCC) patients in living-donor liver transplantation (LDLT). From October 2000 to November 2011, 224 patients who underwent living donor liver transplantation for HCC at our institution were enrolled in this study. We analyzed disease-free survival (DFS) and overall survival (OS) after LT in patients with HCC and designed a new score model using pretransplant neutrophil-lymphocyte ratio (NLR) and C-reactive protein (CRP). The DFS and OS in patients with an NLR level ≥ 6.0 or CRP level ≥ 1.0 were significantly worse than those of patients with an NLR level < 6.0 or CRP level < 1.0 (P = 0.049, P = 0.003 for NLR and P = 0.010, P < 0.001 for CRP, respectively). Using a new score model using the pretransplant NLR and CRP, we can differentiate HCC patients beyond the Milan criteria with a good prognosis from those with a poor prognosis. Combined with the Milan criteria, new score model using NLR and CRP represent new selection criteria for LDLT candidates with HCC, especially beyond the Milan criteria.

Evaluation of SNP Data from the Malus Infinium Array Identifies Challenges for Genetic Analysis of Complex Genomes of Polyploid Origin

PubMed Central

Troggio, Michela; Šurbanovski, Nada; Bianco, Luca; Moretto, Marco; Giongo, Lara; Banchi, Elisa; Viola, Roberto; Fernández, Felicdad Fernández; Costa, Fabrizio; Velasco, Riccardo; Cestaro, Alessandro; Sargent, Daniel James

2013-01-01

High throughput arrays for the simultaneous genotyping of thousands of single-nucleotide polymorphisms (SNPs) have made the rapid genetic characterisation of plant genomes and the development of saturated linkage maps a realistic prospect for many plant species of agronomic importance. However, the correct calling of SNP genotypes in divergent polyploid genomes using array technology can be problematic due to paralogy, and to divergence in probe sequences causing changes in probe binding efficiencies. An Illumina Infinium II whole-genome genotyping array was recently developed for the cultivated apple and used to develop a molecular linkage map for an apple rootstock progeny (M432), but a large proportion of segregating SNPs were not mapped in the progeny, due to unexpected genotype clustering patterns. To investigate the causes of this unexpected clustering we performed BLAST analysis of all probe sequences against the ‘Golden Delicious’ genome sequence and discovered evidence for paralogous annealing sites and probe sequence divergence for a high proportion of probes contained on the array. Following visual re-evaluation of the genotyping data generated for 8,788 SNPs for the M432 progeny using the array, we manually re-scored genotypes at 818 loci and mapped a further 797 markers to the M432 linkage map. The newly mapped markers included the majority of those that could not be mapped previously, as well as loci that were previously scored as monomorphic, but which segregated due to divergence leading to heterozygosity in probe annealing sites. An evaluation of the 8,788 probes in a diverse collection of Malus germplasm showed that more than half the probes returned genotype clustering patterns that were difficult or impossible to interpret reliably, highlighting implications for the use of the array in genome-wide association studies. PMID:23826289

Association mapping of iron deficiency chlorosis loci in soybean (Glycine max L. Merr.) advanced breeding lines.

PubMed

Wang, Ju; McClean, Phillip E; Lee, Rian; Goos, R Jay; Helms, Ted

2008-04-01

Association mapping is an alternative to mapping in a biparental population. A key to successful association mapping is to avoid spurious associations by controlling for population structure. Confirming the marker/trait association in an independent population is necessary for the implementation of the marker in other genetic studies. Two independent soybean populations consisting of advanced breeding lines representing the diversity within maturity groups 00, 0, and I were screened in multi-site, replicated field trials to discover molecular markers associated with iron deficiency chlorosis (IDC), a major yield-limiting factor in soybean. Lines with extreme phenotypes were initially screened to identify simple sequence repeat (SSR) markers putatively associated with the IDC. Marker data collected from all lines were used to control for population structure and kinship relationships. Single factor analysis of variance (SFA) and mixed linear model (MLM) analyses were used to discover marker/trait associations. The MLM analyses, which include population structure, kinship or both factors, reduced the number of markers significantly associated with IDC by 50% compared with SFA. With the MLM approach, three markers were found to be associated with IDC in the first population. Two of these markers, Satt114 and Satt239, were also found to be associated with IDC in the second confirmation population. For both populations, those lines with the tolerance allele at both these two marker loci had significantly lower IDC scores than lines with one or no tolerant alleles.

Comparison of L-system applications towards plant modelling, music rendering and score generation using visual language programming

NASA Astrophysics Data System (ADS)

Lim, Chen Kim; Tan, Kian Lam; Yusran, Hazwanni; Suppramaniam, Vicknesh

2017-10-01

Visual language or visual representation has been used in the past few years in order to express the knowledge in graphic. One of the important graphical elements is fractal and L-Systems is a mathematic-based grammatical model for modelling cell development and plant topology. From the plant model, L-Systems can be interpreted as music sound and score. In this paper, LSound which is a Visual Language Programming (VLP) framework has been developed to model plant to music sound and generate music score and vice versa. The objectives of this research has three folds: (i) To expand the grammar dictionary of L-Systems music based on visual programming, (ii) To design and produce a user-friendly and icon based visual language framework typically for L-Systems musical score generation which helps the basic learners in musical field and (iii) To generate music score from plant models and vice versa using L-Systems method. This research undergoes a four phases methodology where the plant is first modelled, then the music is interpreted, followed by the output of music sound through MIDI and finally score is generated. LSound is technically compared to other existing applications in the aspects of the capability of modelling the plant, rendering the music and generating the sound. It has been found that LSound is a flexible framework in which the plant can be easily altered through arrow-based programming and the music score can be altered through the music symbols and notes. This work encourages non-experts to understand L-Systems and music hand-in-hand.

Fatty acid receptor GPR120: a novel marker for human melanoma.

PubMed

Kleemann, Johannes; Hrgovic, Igor; Ter-Nedden, Jan; Kleimann, Pia; Steinhorst, Katja; Härle, Katja; Müller, Jutta; Kaufmann, Roland; Meissner, Markus; Kippenberger, Stefan

2018-03-21

The correlation between ultraviolet radiation of the skin and melanoma incidence in humans is well established. Interestingly, epidemiologic data suggest also a correlation to an increased BMI pointing to metabolic trigger factors in melanoma pathogenesis. To substantiate this connection, we studied the expression of G-protein-coupled receptor 120 (GPR120), a receptor sensitive to unsaturated long-chain free fatty acids in melanoma tissues. One-hundred fourteen tissue sections histologically confirmed as nevi (n=32), primary melanoma (n=39), and melanoma metastasis (n=43) were immunohistochemically stained against GPR120. The staining was evaluated by three trained dermatopathologists and independently scored. Compared with nevi, primary melanoma and melanoma metastasis showed significantly higher levels of GPR120 staining. Only three out of 32 nevi showed strong GPR120 expression [median immunoreactivity-scoring system (IRS) score: 1, range: 0-10], whereas in primary melanomas 14 out of 39 were highly GPR120-positive (median IRS score: 7, range: 0-12) and in melanoma metastasis 27 out of 43 were highly GPR120-positive (median IRS score: 9, range: 0-12). GPR120 expression and tumor thickness (mm) show a statistically significant correlation in primary melanoma (P=0.011). Moreover, GPR120-positive staining was found throughout the epidermis and in sebaceous and sweat glands, which is yet not described. This study identified GPR120 as a novel marker for melanoma, indicating that melanoma cells are sensitive to free fatty acids. It is tempting to speculate that pharmacologically interfering with GPR120 signaling might improve melanoma therapy.

Pressure pain sensitivity as a marker for stress and pressure pain sensitivity-guided stress management in women with primary breast cancer.

PubMed

Axelsson, Christen K; Ballegaard, Søren; Karpatschof, Benny; Schousen, Peer

2014-08-01

To validate (1) Pressure Pain Sensitivity (PPS) as a marker for stress and (2) a PPS-guided intervention in women with primary Breast Cancer (BC). (1) A total of 58 women with BC were examined before and after 6 months of intervention. A control group of 165 women office employees was divided in a High Stress Group (HSG, n = 37) and a Low Stress Group (LSG, n = 128) to evaluate the association between PPS, questionnaire-related Quality of Life (QOL) and self-evaluated stress. (2) A PPS-guided stress management program (n = 40) was compared to a Psychosocial Group Intervention (PGI, n = 91) and no treatment (n = 86) with respect to a European Organization for Research and Treatment of Cancer (EORTC) questionnaire measured QOL. (1) Resting PPS and changes in PPS during the intervention period correlated significantly to EORTC and Short Form 36 (SF 36) main scores: (all p < 0.05). Between BC, HSG and LSG there was a significant and positive correlation with respect to PPS, SF 36 main scores, depression, and clinical stress scores (all p < 0.05). However, the BC group scored significantly lower than both HSG and LSG (both p < 0.05) with respect to self-evaluated stress. (2) The PPS-guided intervention group improved EORTC main score, pain and nausea, when compared to the control groups (all p < 0.05). PPS was positively associated with QOL, which was in contrast to self-evaluated stress. PPS-guided intervention improved QOL in women with breast cancer.

Tracing prehistoric activities: musculoskeletal stress marker analysis of a Stone-Age population on the island of Gotland in the Baltic sea.

PubMed

Molnar, Petra

2006-01-01

The skeletal remains from the Middle Neolithic (2750-2300 BC) burial ground at Ajvide, Gotland, are analyzed in order to explore musculoskeletal patterns and to attempt to trace general as well as three specific prehistoric activities (archery, harpooning, and kayaking) that are likely to have been performed in this marine setting of fishing, hunting, and gathering. Scoring of muscular and ligament attachments is performed using the scoring method of Hawkey and Merbs ([1995] Int. J. Osteoarchaeol. 5:324-338) for muskuloskeletal stress markers (MSM). The skeletal material consists of 24 male and 15 female adult individuals divided into three age groups: young (<24 years), middle (25-39 years), and old (>40 years). Thirty upper body MSM sites, on both the left and right sides, are scored and form the basis of the study. Results show that males most frequently have higher mean MSM scores than females. Bilateral asymmetry was noted as low in both sexes. Age proved to be a contributing factor to increased MSM scores, with a greater age-related increase in females. MSM patterns were analyzed statistically in muscle groups associated with the three investigated activities. Significant positive correlations were observed in male individuals in muscle groups associated with archery and to some extent harpooning, an indication that these activities would mainly have been performed by men. Correlations in kayaking muscles were not evidently consistent with the kayaking motion. Furthermore, the costoclavicular ligament, often referred to in connection with "kayaker's clavicle," showed no positive statistical correlation with the kayaking muscles.

Comparison of multipoint linkage analyses for quantitative traits in the CEPH data: parametric LOD scores, variance components LOD scores, and Bayes factors.

PubMed

Sung, Yun Ju; Di, Yanming; Fu, Audrey Q; Rothstein, Joseph H; Sieh, Weiva; Tong, Liping; Thompson, Elizabeth A; Wijsman, Ellen M

2007-01-01

We performed multipoint linkage analyses with multiple programs and models for several gene expression traits in the Centre d'Etude du Polymorphisme Humain families. All analyses provided consistent results for both peak location and shape. Variance-components (VC) analysis gave wider peaks and Bayes factors gave fewer peaks. Among programs from the MORGAN package, lm_multiple performed better than lm_markers, resulting in less Markov-chain Monte Carlo (MCMC) variability between runs, and the program lm_twoqtl provided higher LOD scores by also including either a polygenic component or an additional quantitative trait locus.

Comparison of multipoint linkage analyses for quantitative traits in the CEPH data: parametric LOD scores, variance components LOD scores, and Bayes factors

PubMed Central

Sung, Yun Ju; Di, Yanming; Fu, Audrey Q; Rothstein, Joseph H; Sieh, Weiva; Tong, Liping; Thompson, Elizabeth A; Wijsman, Ellen M

2007-01-01

We performed multipoint linkage analyses with multiple programs and models for several gene expression traits in the Centre d'Etude du Polymorphisme Humain families. All analyses provided consistent results for both peak location and shape. Variance-components (VC) analysis gave wider peaks and Bayes factors gave fewer peaks. Among programs from the MORGAN package, lm_multiple performed better than lm_markers, resulting in less Markov-chain Monte Carlo (MCMC) variability between runs, and the program lm_twoqtl provided higher LOD scores by also including either a polygenic component or an additional quantitative trait locus. PMID:18466597

Sequence information signal processor

DOEpatents

Peterson, John C.; Chow, Edward T.; Waterman, Michael S.; Hunkapillar, Timothy J.

1999-01-01

An electronic circuit is used to compare two sequences, such as genetic sequences, to determine which alignment of the sequences produces the greatest similarity. The circuit includes a linear array of series-connected processors, each of which stores a single element from one of the sequences and compares that element with each successive element in the other sequence. For each comparison, the processor generates a scoring parameter that indicates which segment ending at those two elements produces the greatest degree of similarity between the sequences. The processor uses the scoring parameter to generate a similar scoring parameter for a comparison between the stored element and the next successive element from the other sequence. The processor also delivers the scoring parameter to the next processor in the array for use in generating a similar scoring parameter for another pair of elements. The electronic circuit determines which processor and alignment of the sequences produce the scoring parameter with the highest value.

A Toolkit for bulk PCR-based marker design from next-generation sequence data: application for development of a framework linkage map in bulb onion (Allium cepa L.)

PubMed Central

2012-01-01

Background Although modern sequencing technologies permit the ready detection of numerous DNA sequence variants in any organisms, converting such information to PCR-based genetic markers is hampered by a lack of simple, scalable tools. Onion is an example of an under-researched crop with a complex, heterozygous genome where genome-based research has previously been hindered by limited sequence resources and genetic markers. Results We report the development of generic tools for large-scale web-based PCR-based marker design in the Galaxy bioinformatics framework, and their application for development of next-generation genetics resources in a wide cross of bulb onion (Allium cepa L.). Transcriptome sequence resources were developed for the homozygous doubled-haploid bulb onion line ‘CUDH2150’ and the genetically distant Indian landrace ‘Nasik Red’, using 454™ sequencing of normalised cDNA libraries of leaf and shoot. Read mapping of ‘Nasik Red’ reads onto ‘CUDH2150’ assemblies revealed 16836 indel and SNP polymorphisms that were mined for portable PCR-based marker development. Tools for detection of restriction polymorphisms and primer set design were developed in BioPython and adapted for use in the Galaxy workflow environment, enabling large-scale and targeted assay design. Using PCR-based markers designed with these tools, a framework genetic linkage map of over 800cM spanning all chromosomes was developed in a subset of 93 F2 progeny from a very large F2 family developed from the ‘Nasik Red’ x ‘CUDH2150’ inter-cross. The utility of tools and genetic resources developed was tested by designing markers to transcription factor-like polymorphic sequences. Bin mapping these markers using a subset of 10 progeny confirmed the ability to place markers within 10 cM bins, enabling increased efficiency in marker assignment and targeted map refinement. The major genetic loci conditioning red bulb colour (R) and fructan content (Frc) were located on this map by QTL analysis. Conclusions The generic tools developed for the Galaxy environment enable rapid development of sets of PCR assays targeting sequence variants identified from Illumina and 454 sequence data. They enable non-specialist users to validate and exploit large volumes of next-generation sequence data using basic equipment. PMID:23157543

A toolkit for bulk PCR-based marker design from next-generation sequence data: application for development of a framework linkage map in bulb onion (Allium cepa L.).

PubMed

Baldwin, Samantha; Revanna, Roopashree; Thomson, Susan; Pither-Joyce, Meeghan; Wright, Kathryn; Crowhurst, Ross; Fiers, Mark; Chen, Leshi; Macknight, Richard; McCallum, John A

2012-11-19

Although modern sequencing technologies permit the ready detection of numerous DNA sequence variants in any organisms, converting such information to PCR-based genetic markers is hampered by a lack of simple, scalable tools. Onion is an example of an under-researched crop with a complex, heterozygous genome where genome-based research has previously been hindered by limited sequence resources and genetic markers. We report the development of generic tools for large-scale web-based PCR-based marker design in the Galaxy bioinformatics framework, and their application for development of next-generation genetics resources in a wide cross of bulb onion (Allium cepa L.). Transcriptome sequence resources were developed for the homozygous doubled-haploid bulb onion line 'CUDH2150' and the genetically distant Indian landrace 'Nasik Red', using 454™ sequencing of normalised cDNA libraries of leaf and shoot. Read mapping of 'Nasik Red' reads onto 'CUDH2150' assemblies revealed 16836 indel and SNP polymorphisms that were mined for portable PCR-based marker development. Tools for detection of restriction polymorphisms and primer set design were developed in BioPython and adapted for use in the Galaxy workflow environment, enabling large-scale and targeted assay design. Using PCR-based markers designed with these tools, a framework genetic linkage map of over 800cM spanning all chromosomes was developed in a subset of 93 F(2) progeny from a very large F(2) family developed from the 'Nasik Red' x 'CUDH2150' inter-cross. The utility of tools and genetic resources developed was tested by designing markers to transcription factor-like polymorphic sequences. Bin mapping these markers using a subset of 10 progeny confirmed the ability to place markers within 10 cM bins, enabling increased efficiency in marker assignment and targeted map refinement. The major genetic loci conditioning red bulb colour (R) and fructan content (Frc) were located on this map by QTL analysis. The generic tools developed for the Galaxy environment enable rapid development of sets of PCR assays targeting sequence variants identified from Illumina and 454 sequence data. They enable non-specialist users to validate and exploit large volumes of next-generation sequence data using basic equipment.

Association between spirometry controlled chest CT scores using computer-animated biofeedback and clinical markers of lung disease in children with cystic fibrosis.

PubMed

Kongstad, Thomas; Green, Kent; Buchvald, Frederik; Skov, Marianne; Pressler, Tania; Nielsen, Kim Gjerum

2017-01-01

Background : Computed tomography (CT) of the lungs is the gold standard for assessing the extent of structural changes in the lungs. Spirometry-controlled chest CT (SCCCT) has improved the usefulness of CT by standardising inspiratory and expiratory lung volumes during imaging. This was a single-centre cross-sectional study in children with cystic fibrosis (CF). Using SCCCT we wished to investigate the association between the quantity and extent of structural lung changes and pulmonary function outcomes, and prevalence of known CF lung pathogens. Methods : CT images were analysed by CF-CT scoring (expressed as % of maximum score) to quantify different aspects of structural lung changes including bronchiectasis, airway wall thickening, mucus plugging, opacities, cysts, bullae and gas trapping. Clinical markers consisted of outcomes from pulmonary function tests, microbiological cultures from sputum and serological samples reflecting anti-bacterial and anti-fungal antibodies. Results : Sixty-four children with CF, median age (range) of 12.7 (6.4-18.1) years, participated in the study. The median (range) CF-CT total score in all children was 9.3% (0.4-46.8) with gas trapping of 40.7% (3.7-100) as the most abundant finding. Significantly higher median CF-CT total scores (21.9%) were found in patients with chronic infections ( N  = 12) including Gram-negative infection and allergic bronchopulmonary aspergillosis (ABPA) exhibiting CF-CT total scores of 14.2% (ns) and 24.0% ( p  < 0.01), respectively, compared to 8.0% in patients with no chronic lung infection. Lung clearance index (LCI) derived from multiple breath washout exhibited closest association with total CF-CT scores, compared to other pulmonary function outcomes. Conclusions : The most prominent structural lung change was gas trapping, while CF-CT total scores were generally low, both showing close association with LCI. Chronic lung infections, specifically in the form of ABPA, were associated with increased scores in lung changes. Further investigation of impact of infections with different microorganisms on extent and progression of structural CF lung disease is needed.

Anti-RAINBOW dye-specific antibodies as universal tools for the visualization of prestained protein molecular weight markers in Western blot analysis.

PubMed

Schüchner, Stefan; Andorfer, Peter; Mudrak, Ingrid; Ogris, Egon

2016-08-17

Western blotting is one of the most widely used techniques in molecular biology and biochemistry. Prestained proteins are used as molecular weight standards in protein electrophoresis. In the chemiluminescent Western blot analysis, however, these colored protein markers are invisible leaving researchers with the unsatisfying situation that the signal for the protein of interest and the signal for the markers are not captured simultaneously and have to be merged in an error-prone step. To allow the simultaneous detection of marker proteins we generated monoclonal antibodies specific for the protein dyes. To elicit a dye rather than protein specific immune response we immunized mice sequentially with dye-carrier protein complexes, in which a new carrier protein was used for each subsequent immunization. Moreover, by sequentially immunizing with dye-carrier protein complexes, in which different but structurally related dyes were used, we could also generate an antibody, termed anti-RAINBOW, that cross-reacted even with structurally related dyes not used in the immunizations. Our novel antibodies represent convenient tools for the simultaneous Western blot detection of commercially available prestained marker proteins in combination with the detection of any specific protein of interest. These antibodies will render obsolete the anachronistic tradition of manually charting marker bands on film.

Distribution of mating-type alleles and M13 PCR markers in the black leaf spot fungus Mycosphaerella fijiensis of bananas in Brazil.

PubMed

Queiroz, C B; Miranda, E C; Hanada, R E; Sousa, N R; Gasparotto, L; Soares, M A; Silva, G F

2013-02-08

The fungus Mycosphaerella fijiensis is the causative agent of black sigatoka, which is one of the most destructive diseases of banana plants. Infection with this pathogen results in underdeveloped fruit, with no commercial value. We analyzed the distribution of the M. fijiensis mating-type system and its genetic variability using M13 phage DNA markers. We found a 1:1 distribution of mating-type alleles, indicating MAT1-1 and MAT1-2 idiomorphs. A polymorphism analysis using three different primers for M13 markers showed that only the M13 minisatellite primers generated polymorphic products. We then utilized this polymorphism to characterize 40 isolates from various Brazilian states. The largest genetic distances were found between isolates from the same location and between isolates from different parts of the country. Therefore, there was no correlation between the genetic similarity and the geographic origin of the isolates. The M13 marker was used to generate genetic fingerprints for five isolates; these fingerprints were compared with the band profiles obtained from inter-simple sequence repeat (UBC861) and inter-retrotransposon amplified polymorphism analyses. We found that the M13 marker was more effective than the other two markers for differentiating these isolates.

Anti-RAINBOW dye-specific antibodies as universal tools for the visualization of prestained protein molecular weight markers in Western blot analysis

PubMed Central

Schüchner, Stefan; Andorfer, Peter; Mudrak, Ingrid; Ogris, Egon

2016-01-01

Western blotting is one of the most widely used techniques in molecular biology and biochemistry. Prestained proteins are used as molecular weight standards in protein electrophoresis. In the chemiluminescent Western blot analysis, however, these colored protein markers are invisible leaving researchers with the unsatisfying situation that the signal for the protein of interest and the signal for the markers are not captured simultaneously and have to be merged in an error-prone step. To allow the simultaneous detection of marker proteins we generated monoclonal antibodies specific for the protein dyes. To elicit a dye rather than protein specific immune response we immunized mice sequentially with dye-carrier protein complexes, in which a new carrier protein was used for each subsequent immunization. Moreover, by sequentially immunizing with dye-carrier protein complexes, in which different but structurally related dyes were used, we could also generate an antibody, termed anti-RAINBOW, that cross-reacted even with structurally related dyes not used in the immunizations. Our novel antibodies represent convenient tools for the simultaneous Western blot detection of commercially available prestained marker proteins in combination with the detection of any specific protein of interest. These antibodies will render obsolete the anachronistic tradition of manually charting marker bands on film. PMID:27531616

Distinguishing body mass and activity level from the lower limb: can entheses diagnose obesity?

PubMed

Godde, Kanya; Taylor, Rebecca Wilson

2013-03-10

The ability to estimate body size from the skeleton has broad applications, but is especially important to the forensic community when identifying unknown skeletal remains. This research investigates the utility of using entheses/muscle skeletal markers of the lower limb to estimate body size and to classify individuals into average, obese, and active categories, while using a biomechanical approach to interpret the results. Eighteen muscle attachment sites of the lower limb, known to be involved in the sit-to-stand transition, were scored for robusticity and stress in 105 white males (aged 31-81 years) from the William M. Bass Donated Skeletal Collection. Both logistic regression and log linear models were applied to the data to (1) test the utility of entheses as an indicator of body weight and activity level, and (2) to generate classification percentages that speak to the accuracy of the method. Thirteen robusticity scores differed significantly between the groups, but classification percentages were only slightly greater than chance. However, clear differences could be seen between the average and obese and the average and active groups. Stress scores showed no value in discriminating between groups. These results were interpreted in relation to biomechanical forces at the microscopic and macroscopic levels. Even though robusticity alone is not able to classify individuals well, its significance may show greater value when incorporated into a model that has multiple skeletal indicators. Further research needs to evaluate a larger sample and incorporate several lines of evidence to improve classification rates. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Role of autoimmunity in nonviral chronic liver disease.

PubMed

Amarapurkar, D N; Amarapurkar, A D

2000-11-01

To evaluate the prevalence and clinical profile of autoimmune hepatitis (AIH) in patients with chronic liver disease. Four hundred and thirty five consecutive patient with chronic liver disease seen in our department from January 1997 to December 1998 were studied with detailed history and clinical examination. All the patients underwent liver function tests, ultrasonography, isotope liver scanning, viral markers, autoimmune markers ANA, ASMA, LKM1 and AMA (by immunofluorescence technique) and liver histology whenever permissible. Appropriate work up for Wilson's disease was done whenever suspected clinically. Diagnosis of autoimmune hepatitis was made by the composite scoring system by international autoimmune hepatitis group. Twenty out of the 435 patients met the criteria of definite autoimmune hepatitis and seven patient had probable autoimmune hepatitis. Forty out of 408 patients showed markers of autoimmunity positive but did not qualify diagnosis of AIH on composite scores. Demographic profile of 27 patients with autoimmune hepatitis was as follows; male:female ratio 1:8, mean age 39.8 +/- 13 years (Range 4-65 years); mode of presentation as cirrhosis 11/27 (40.7%), chronic hepatitis 12/27 (44.4%) and acute hepatitis 4/27 (14.8%). Elevated serum bilirubin levels were seen in 12 (44.4%) patients while mean serum aminotransferases levels were 249 +/- 343 and 262 +/- 418 respectively. Other disease associations seen were as follows: diabetes in 4 (14.8%), rheumatoid arthritis in 3 (11%), hypothyroidism in 2 (7.4%) and ulcerative colitis in 1 (3.7%). The pattern of autoimmune markers was ANA +ve 23/27 (85%) (+ve titres of ANA > 1:80 in adults and 1:20 in children), ASMA +ve in 16/27 (59.2%) (+ve titres of ASMA > 1:40) and LKM1 in 3 patients. AMA in tires less than 1:80 was found in 3 patients. Liver histology changes seen were lymphoplasmacytic infiltrates (100%), bridging necrosis (93%), liver cell rossetting (80%) and fibrosis with or without cirrhosis (50%). Autoimmune liver disease is not uncommon in India and should be suspected in all patients with chronic liver disease, especially in non-viral, non-alcoholic, female patients. The diagnosis of AIH should however be made on the composite scoring system given by international group and not only on the presence or absence of autoimmune markers.

Lipid-lysine adducts and modified tyrosines as markers of oxidative stress in the second trimester of pregnancy and their association with infant characteristics

PubMed Central

REJC, BARBARA; KATO, YOJI; KARAS-KUZELICKI, NATASA; OSREDKAR, JOSKO; GERSAK, KSENIJA

2016-01-01

Pregnancy is a physiological state accompanied by excessive levels of oxidative stress (OS), due to the increased demand and utilisation of oxygen. There is increasing evidence that maternally augmented OS exerts an adverse effect on pregnancy outcome. The aim of the present prospective study was to determine the association between the urinary concentration of relatively novel OS markers measured in the second trimester of pregnancy and the infant characteristics at birth. The maternal levels of urinary hexanoyl-lysine (HEL), propanoyl-lysine (PRL), dityrosine (DiY) and 3-nitrotyrosine (NY) were evaluated in generally healthy pregnant subjects to determine their association with birth weight, gestation at delivery and Apgar score. The observed levels of the markers were in agreement with those measured in healthy non-pregnant subjects in a previous study. A positive correlation was detected between HEL and PRL, as well as between HEL and DiY. Although the absence of a correlation between NY and the other markers has been previously noted in a non-pregnant population, a positive correlation in the pair PRL-NY (r=0.367; P<0.001) was observed in the present study. Maternal cigarette smoking was associated with increased urinary PRL levels (P=0.034). The most notable observation in the present study was that high levels of PRL and NY were associated with low Apgar scores at 1 and 5 min after birth (OR, 1.098 and 2.084 for PRL and NY, respectively; P<0.05). However, poor predictive accuracy was shown. For NY, the following results were obtained: Area under the curve (AUC), 0.818; sensitivity, 100%; specificity, 57%; positive predictive value (PPV), 11.54%; and negative predictive value (NPV), 100%. For PLR the values were as follows: AUC, 0.802; sensitivity, 100%; specificity, 62.6%; PPV, 13.05%; and NPV, 100%. DiY was negatively associated with preterm birth risk (OR=0.703; P=0.028). In conclusion, the results of the present study indicated the presence of OS in the second trimester of pregnancy, which was detected with damage to lipids and proteins and associated with an adverse Apgar score; however, the selected urinary markers exhibited poor positive predictive efficacy. PMID:26997995

Lipid-lysine adducts and modified tyrosines as markers of oxidative stress in the second trimester of pregnancy and their association with infant characteristics.

PubMed

Rejc, Barbara; Kato, Yoji; Karas-Kuzelicki, Natasa; Osredkar, Josko; Gersak, Ksenija

2016-03-01

Pregnancy is a physiological state accompanied by excessive levels of oxidative stress (OS), due to the increased demand and utilisation of oxygen. There is increasing evidence that maternally augmented OS exerts an adverse effect on pregnancy outcome. The aim of the present prospective study was to determine the association between the urinary concentration of relatively novel OS markers measured in the second trimester of pregnancy and the infant characteristics at birth. The maternal levels of urinary hexanoyl-lysine (HEL), propanoyl-lysine (PRL), dityrosine (DiY) and 3-nitrotyrosine (NY) were evaluated in generally healthy pregnant subjects to determine their association with birth weight, gestation at delivery and Apgar score. The observed levels of the markers were in agreement with those measured in healthy non-pregnant subjects in a previous study. A positive correlation was detected between HEL and PRL, as well as between HEL and DiY. Although the absence of a correlation between NY and the other markers has been previously noted in a non-pregnant population, a positive correlation in the pair PRL-NY (r=0.367; P<0.001) was observed in the present study. Maternal cigarette smoking was associated with increased urinary PRL levels (P=0.034). The most notable observation in the present study was that high levels of PRL and NY were associated with low Apgar scores at 1 and 5 min after birth (OR, 1.098 and 2.084 for PRL and NY, respectively; P<0.05). However, poor predictive accuracy was shown. For NY, the following results were obtained: Area under the curve (AUC), 0.818; sensitivity, 100%; specificity, 57%; positive predictive value (PPV), 11.54%; and negative predictive value (NPV), 100%. For PLR the values were as follows: AUC, 0.802; sensitivity, 100%; specificity, 62.6%; PPV, 13.05%; and NPV, 100%. DiY was negatively associated with preterm birth risk (OR=0.703; P=0.028). In conclusion, the results of the present study indicated the presence of OS in the second trimester of pregnancy, which was detected with damage to lipids and proteins and associated with an adverse Apgar score; however, the selected urinary markers exhibited poor positive predictive efficacy.

Principal components derived from CSF inflammatory profiles predict outcome in survivors after severe traumatic brain injury.

PubMed

Kumar, Raj G; Rubin, Jonathan E; Berger, Rachel P; Kochanek, Patrick M; Wagner, Amy K

2016-03-01

Studies have characterized absolute levels of multiple inflammatory markers as significant risk factors for poor outcomes after traumatic brain injury (TBI). However, inflammatory marker concentrations are highly inter-related, and production of one may result in the production or regulation of another. Therefore, a more comprehensive characterization of the inflammatory response post-TBI should consider relative levels of markers in the inflammatory pathway. We used principal component analysis (PCA) as a dimension-reduction technique to characterize the sets of markers that contribute independently to variability in cerebrospinal (CSF) inflammatory profiles after TBI. Using PCA results, we defined groups (or clusters) of individuals (n=111) with similar patterns of acute CSF inflammation that were then evaluated in the context of outcome and other relevant CSF and serum biomarkers collected days 0-3 and 4-5 post-injury. We identified four significant principal components (PC1-PC4) for CSF inflammation from days 0-3, and PC1 accounted for the greatest (31%) percentage of variance. PC1 was characterized by relatively higher CSF sICAM-1, sFAS, IL-10, IL-6, sVCAM-1, IL-5, and IL-8 levels. Cluster analysis then defined two distinct clusters, such that individuals in cluster 1 had highly positive PC1 scores and relatively higher levels of CSF cortisol, progesterone, estradiol, testosterone, brain derived neurotrophic factor (BDNF), and S100b; this group also had higher serum cortisol and lower serum BDNF. Multinomial logistic regression analyses showed that individuals in cluster 1 had a 10.9 times increased likelihood of GOS scores of 2/3 vs. 4/5 at 6 months compared to cluster 2, after controlling for covariates. Cluster group did not discriminate between mortality compared to GOS scores of 4/5 after controlling for age and other covariates. Cluster groupings also did not discriminate mortality or 12 month outcomes in multivariate models. PCA and cluster analysis establish that a subset of CSF inflammatory markers measured in days 0-3 post-TBI may distinguish individuals with poor 6-month outcome, and future studies should prospectively validate these findings. PCA of inflammatory mediators after TBI could aid in prognostication and in identifying patient subgroups for therapeutic interventions. Copyright © 2015 Elsevier Inc. All rights reserved.

The Role of eIF4E Activity in Breast Cancer

DTIC Science & Technology

2010-08-01

marker with some success. Furthermore, eIF4E is an established target for cancer therapy [3] and clinical trials of the efficacy and safety of cancer...individual group was small, for overall survival (OS), disease-free survival (DFS) and disease- specific survival ( DSS ) (Figure 2). High eIF4E scores were...indicative of poor prognosis. Prognosis seemed to worsen with each increasing eIF4E score for OS, whereas patterns for DFS and DSS sug- gested weaker

Behavioural markers for autism in infancy: scores on the Autism Observational Scale for Infants in a prospective study of at-risk siblings.

PubMed

Gammer, Isobel; Bedford, Rachael; Elsabbagh, Mayada; Garwood, Holly; Pasco, Greg; Tucker, Leslie; Volein, Agnes; Johnson, Mark H; Charman, Tony

2015-02-01

We investigated early behavioural markers of autism spectrum disorder (ASD) using the Autism Observational Scale for Infants (AOSI) in a prospective familial high-risk (HR) sample of infant siblings (N=54) and low-risk (LR) controls (N=50). The AOSI was completed at 7 and 14 month infant visits and children were seen again at age 24 and 36 months. Diagnostic outcome of ASD (HR-ASD) versus no ASD (HR-No ASD) was determined for the HR sample at the latter timepoint. The HR group scored higher than the LR group at 7 months and marginally but non-significantly higher than the LR group at 14 months, although these differences did not remain when verbal and nonverbal developmental level were covaried. The HR-ASD outcome group had higher AOSI scores than the LR group at 14 months but not 7 months, even when developmental level was taken into account. The HR-No ASD outcome group had scores intermediate between the HR-ASD and LR groups. At both timepoints a few individual items were higher in the HR-ASD and HR-No ASD outcome groups compared to the LR group and these included both social (e.g. orienting to name) and non-social (e.g. visual tracking) behaviours. AOSI scores at 14 months but not at 7 months were moderately correlated with later scores on the autism diagnostic observation schedule (ADOS) suggesting continuity of autistic-like behavioural atypicality but only from the second and not first year of life. The scores of HR siblings who did not go on to have ASD were intermediate between the HR-ASD outcome and LR groups, consistent with the notion of a broader autism phenotype. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Generation of Marker- and/or Backbone-Free Transgenic Wheat Plants via Agrobacterium-Mediated Transformation.

PubMed

Wang, Gen-Ping; Yu, Xiu-Dao; Sun, Yong-Wei; Jones, Huw D; Xia, Lan-Qin

2016-01-01

Horizontal transfer of antibiotic resistance genes to animals and vertical transfer of herbicide resistance genes to the weedy relatives are perceived as major biosafety concerns in genetically modified (GM) crops. In this study, five novel vectors which used gusA and bar as a reporter gene and a selection marker gene, respectively, were constructed based on the pCLEAN dual binary vector system. Among these vectors, 1G7B and 5G7B carried two T-DNAs located on two respective plasmids with 5G7B possessing an additional virGwt gene. 5LBTG154 and 5TGTB154 carried two T-DNAs in the target plasmid with either one or double right borders, and 5BTG154 carried the selectable marker gene on the backbone outside of the T-DNA left border in the target plasmid. In addition, 5BTG154, 5LBTG154, and 5TGTB154 used pAL154 as a helper plasmid which contains Komari fragment to facilitate transformation. These five dual binary vector combinations were transformed into Agrobacterium strain AGL1 and used to transform durum wheat cv Stewart 63. Evaluation of the co-transformation efficiencies, the frequencies of marker-free transgenic plants, and integration of backbone sequences in the obtained transgenic lines indicated that two vectors (5G7B and 5TGTB154) were more efficient in generating marker-free transgenic wheat plants with no or minimal integration of backbone sequences in the wheat genome. The vector series developed in this study for generation of marker- and/or backbone-free transgenic wheat plants via Agrobacterium -mediated transformation will be useful to facilitate the creation of "clean" GM wheat containing only the foreign genes of agronomic importance.

Classical swine fever vaccines-State-of-the-art.

PubMed

Blome, Sandra; Moß, Claudia; Reimann, Ilona; König, Patricia; Beer, Martin

2017-07-01

Due to its impact on animal health and pig industry, classical swine fever (CSF) is still one of the most important viral diseases of pigs. To control the disease, safe and highly efficacious live attenuated vaccines exist for decades. These vaccines have usually outstanding efficacy and safety but lack differentiability of infected from vaccinated animals (DIVA or marker strategy). In contrast, the first generation of E2 subunit marker vaccines shows constraints in efficacy, application, and production. To overcome these limitations, new generations of marker vaccines are developed. A wide range of approaches have been tried including recombinant vaccines, recombinant inactivated vaccines or subunit vaccines, vector vaccines, and DNA/RNA vaccines. During the last years, especially attenuated deletion vaccines or chimeric constructs have shown potential. At present, especially two new constructs have been intensively tested, the adenovirus-delivered, Semliki Forest virus replicon-vectored marker vaccine candidate "rAdV-SFV-E2" and the pestivirus chimera "CP7_E2alf". The later was recently licensed by the European Medicines Agency. Under field conditions, all marker vaccines have to be accompanied by a potent test system. Particularly this point shows still weaknesses and it is important to embed vaccination in a well-established vaccination strategy and a suitable diagnostic workflow. In summary, conventional vaccines are a standard in terms of efficacy. However, only vaccines with DIVA will allow improved eradication strategies e.g. also under emergency vaccination conditions in free regions. To answer this demand, new generations of marker vaccines have been developed and add now to the tool box of CSF control. Copyright © 2017 Elsevier B.V. All rights reserved.

Human neutral genetic variation and forensic STR data.

PubMed

Silva, Nuno M; Pereira, Luísa; Poloni, Estella S; Currat, Mathias

2012-01-01

The forensic genetics field is generating extensive population data on polymorphism of short tandem repeats (STR) markers in globally distributed samples. In this study we explored and quantified the informative power of these datasets to address issues related to human evolution and diversity, by using two online resources: an allele frequency dataset representing 141 populations summing up to almost 26 thousand individuals; a genotype dataset consisting of 42 populations and more than 11 thousand individuals. We show that the genetic relationships between populations based on forensic STRs are best explained by geography, as observed when analysing other worldwide datasets generated specifically to study human diversity. However, the global level of genetic differentiation between populations (as measured by a fixation index) is about half the value estimated with those other datasets, which contain a much higher number of markers but much less individuals. We suggest that the main factor explaining this difference is an ascertainment bias in forensics data resulting from the choice of markers for individual identification. We show that this choice results in average low variance of heterozygosity across world regions, and hence in low differentiation among populations. Thus, the forensic genetic markers currently produced for the purpose of individual assignment and identification allow the detection of the patterns of neutral genetic structure that characterize the human population but they do underestimate the levels of this genetic structure compared to the datasets of STRs (or other kinds of markers) generated specifically to study the diversity of human populations.

Development of cost-effective Hordeum chilense DNA markers: molecular aids for marker-assisted cereal breeding.

PubMed

Hernández, P; Dorado, G; Ramírez, M C; Laurie, D A; Snape, J W; Martín, A

2003-01-01

Hordeum chilense is a potential source of useful genes for wheat breeding. The use of this wild species to increase genetic variation in wheat will be greatly facilitated by marker-assisted introgression. In recent years, the search for the most suitable DNA marker system for tagging H. chilense genomic regions in a wheat background has lead to the development of RAPD and SCAR markers for this species. RAPDs represent an easy way of quickly generating suitable introgression markers, but their use is limited in heterogeneous wheat genetic backgrounds. SCARs are more specific assays, suitable for automatation or multiplexing. Direct sequencing of RAPD products is a cost-effective approach that reduces labour and costs for SCAR development. The use of SSR and STS primers originally developed for wheat and barley are additional sources of genetic markers. Practical applications of the different marker approaches for obtaining derived introgression products are described.

Elevation of autophagy markers in Sjögren syndrome dry eye.

PubMed

Byun, Yong-Soo; Lee, Hyun Jung; Shin, Soojung; Chung, So-Hyang

2017-12-08

Autophagy is known to be implicated in the pathogenesis of Sjögren syndrome (SS), but evidences are limited. We aimed to examine the levels of autophagy markers in tear film and conjunctival epithelial cells from SS dry eye patients, and analyze their correlations with clinical features. Patients with SS dry eye exhibited lower Schirmer values, lower tear breakup time, and higher ocular staining scores. In tears, ATG5 and LC3B-II/I levels were significantly higher in SS dry eye. ATG5 and LC3B-II mRNA in the conjunctiva were also elevated in SS dry eye compared with non-SS dry eye. The immunostaining of conjunctival epithelium showed a punctate pattern of ATG5 and LC3B-II in SS dry eye. These staining patterns were also observed in the lacrimal gland of SS animal models. ATG5 levels in tears and the conjunctival epithelium strongly correlated with ocular staining scores, and one month of topical corticosteroid treatment reduced both ATG5 and LC3B-II/I levels in tear film and the conjunctival epithelium of patients with SS dry eye. Our results suggest that autophagy is enhanced or dysregulated in SS and autophagy markers may be serve as both diagnostic and therapeutic biomarkers in SS dry eye.

Optimal threshold estimator of a prognostic marker by maximizing a time-dependent expected utility function for a patient-centered stratified medicine.

PubMed

Dantan, Etienne; Foucher, Yohann; Lorent, Marine; Giral, Magali; Tessier, Philippe

2018-06-01

Defining thresholds of prognostic markers is essential for stratified medicine. Such thresholds are mostly estimated from purely statistical measures regardless of patient preferences potentially leading to unacceptable medical decisions. Quality-Adjusted Life-Years are a widely used preferences-based measure of health outcomes. We develop a time-dependent Quality-Adjusted Life-Years-based expected utility function for censored data that should be maximized to estimate an optimal threshold. We performed a simulation study to compare estimated thresholds when using the proposed expected utility approach and purely statistical estimators. Two applications illustrate the usefulness of the proposed methodology which was implemented in the R package ROCt ( www.divat.fr ). First, by reanalysing data of a randomized clinical trial comparing the efficacy of prednisone vs. placebo in patients with chronic liver cirrhosis, we demonstrate the utility of treating patients with a prothrombin level higher than 89%. Second, we reanalyze the data of an observational cohort of kidney transplant recipients: we conclude to the uselessness of the Kidney Transplant Failure Score to adapt the frequency of clinical visits. Applying such a patient-centered methodology may improve future transfer of novel prognostic scoring systems or markers in clinical practice.

Focal Defects of the Knee Articular Surface: Evidence of a Regenerative Potential Pattern in Osteochondritis Dissecans and Degenerative Lesions

PubMed Central

Gabusi, Elena; Manferdini, Cristina; Paolella, Francesca; Gambari, Laura; Mariani, Erminia

2017-01-01

The surgical treatment of knee articular focal lesions may offer heterogeneous clinical results. Osteochondritis dissecans (OCD) lesions showed to heal better than degenerative lesions (DL) but the underlying biological reasons are unknown. We evaluated the basal histological and immunohistochemical characteristics of these lesions analyzing a series of osteochondral fragments from young patients with similar age but presenting different etiology. Osteochondral tissue samples were stained with Safranin O and graded using a histological score. Markers of mesenchymal progenitor cells (CD146), osteoclasts (tartrate-resistant acid phosphatase, TRAP), and vessels (CD34) were evaluated. Histological score showed a higher degeneration of both cartilage and bone compartments in OCD compared to DL fragments. Only CD146-positive cells were found at the same percentage in cartilage compartment of both DL and OCD patients. By contrast, in the bone compartment a significantly higher percentage of CD146, TRAP, and CD34 markers was found in OCD compared to DL patients. These data showed distinct histological characteristics of osteochondral focal lesions located in the same anatomical region but having a different etiology. The higher percentages of these markers in OCD than in DL, mainly associated with a high bone turnover, could help to explain the higher clinical healing potential of OCD patients. PMID:28770227

Detection of QTLs for salt tolerance in Asian barley (Hordeum vulgare L.) by association analysis with SNP markers

PubMed Central

Sbei, Hanen; Sato, Kazuhiro; Shehzad, Tariq; Harrabi, Moncef; Okuno, Kazutoshi

2014-01-01

Two hundred ninety-six Asian barley (Hordeum vulgare L.) accessions were assessed to detect QTLs underlying salt tolerance by association analysis using a 384 single nucleotide polymorphism (SNP) marker system. The experiment was laid out at the seedling stage in a hydroponic solution under control and 250 mM NaCl solution with three replications of four plants each. Salt tolerance was assessed by leaf injury score (LIS) and salt tolerance indices (STIs) of the number of leaves (NL), shoot length (SL), root length (RL), shoot dry weight (SDW) and root dry weight (RDW). LIS was scored from 1 to 5 according to the severity of necrosis and chlorosis observed on leaves. There was a wide variation in salt tolerance among Asian barley accessions. LIS and STI (SDW) were the most suitable traits for screening salt tolerance. Association was estimated between markers and traits to detect QTLs for LIS and STI (SDW). Seven significant QTLs were located on chromosomes 1H (2 QTLs), 2H (2 QTLs), 3H (1 QTL), 4H (1 QTL) and 5H (1 QTL). Five QTLs were associated with LIS and 2 QTLs with STI (SDW). Two QTLs associated with LIS were newly identified on chromosomes 3H and 4H. PMID:25914593

BBD Reference Set Application: Jeffery Marks-Duke (2015) — EDRN Public Portal

Cancer.gov

We propose a pre-validation study for markers that could predict the likelihood of invasive breast cancer following a tissue diagnosis of benign breast pathology (any diagnosis that is less severe than carcinoma in situ). The study is designed to test the utility of a series of markers that were shown to have some predictive value by immunohistochemical staining in other cohorts. These markers include the proliferation associated antigen KI-67, EZH2, PTGS2 (COX2), ALDH1, CDKN2A (p16), HYAL1, MMP1, CEACAM6, and TP53. In addition, we propose analyzing two markers that comprise part of the DCIS Oncotype panel, GSTM1 and progesterone receptor (PR). The study will occur in two EDRN clinical validation center (CVC) laboratories, namely Duke and University of Kansas, and utilize specimens from Northwestern University and Geisinger Health System that have been identified and are either already sectioned or waiting to be sectioned. Results will be scored and returned to the DMCC to determine whether any of the markers or combinations of these markers may have sufficient value to proceed to a second stage validation with large numbers of samples from Geisenger Health Systems and the Henry Ford Hospital.

Direct analysis in real time mass spectrometry and multivariate data analysis: a novel approach to rapid identification of analytical markers for quality control of traditional Chinese medicine preparation.

PubMed

Zeng, Shanshan; Wang, Lu; Chen, Teng; Wang, Yuefei; Mo, Huanbiao; Qu, Haibin

2012-07-06

The paper presents a novel strategy to identify analytical markers of traditional Chinese medicine preparation (TCMP) rapidly via direct analysis in real time mass spectrometry (DART-MS). A commonly used TCMP, Danshen injection, was employed as a model. The optimal analysis conditions were achieved by measuring the contribution of various experimental parameters to the mass spectra. Salvianolic acids and saccharides were simultaneously determined within a single 1-min DART-MS run. Furthermore, spectra of Danshen injections supplied by five manufacturers were processed with principal component analysis (PCA). Obvious clustering was observed in the PCA score plot, and candidate markers were recognized from the contribution plots of PCA. The suitability of potential markers was then confirmed by contrasting with the results of traditional analysis methods. Using this strategy, fructose, glucose, sucrose, protocatechuic aldehyde and salvianolic acid A were rapidly identified as the markers of Danshen injections. The combination of DART-MS with PCA provides a reliable approach to the identification of analytical markers for quality control of TCMP. Copyright © 2012 Elsevier B.V. All rights reserved.

1-Adamantylamine a simple urine marker for screening for third generation adamantyl-type synthetic cannabinoids by ultra-performance liquid chromatography tandem mass spectrometry.

PubMed

Ford, Loretta T; Berg, Jonathan D

2016-11-01

Background Synthetic cannabinoids (NOIDS) are novel psychotropic drugs (NPS) currently freely sold in the United Kingdom as 'research chemicals'. Detection of NOIDS use is not available in current routine methods. Here we describe a marker which helps determine which patients have used these substances. Methods In a test case, ultra-performance liquid chromatography mass spectrometry (UPLC-Tof) was used to screen the legal high Herbal Haze II, the contents of hand-rolled cigarettes and five patient samples for NOIDS and their metabolites. Results Analysis of legal high Herbal Haze II and cigarettes identified the third generation adamantyl-type NOIDS N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (AKB-48), 5F-AKB-48 and N-adamantyl-1-fluoropentylindole-3-carboxamide (STS-135). Out of 18 potential metabolites, 1-adamantylamine (C 10 H 17 N) was detected in all five urine samples. This adamantyl-type NOID marker was incorporated into our routine LC-MS/MS urine screen. Out of 14,436 random urine samples screened over eight months, 296 (2.05%) tested positive for the adamantyl-type NOID marker. Conclusion We have discovered a urine marker for identifying patients smoking legal high products containing the third generation adamantyl-type NOIDS such as AKB-48 and its fluoropentyl analogue 5F-AKB-48, which are among the most popular NOIDS currently available in legal high products sold in UK. This marker can be incorporated into routine LC-MS/MS drug screening alongside classic drugs of abuse. Positive detection rates for this new legal high marker are greater than for established classic drugs that are routinely screened such as amphetamine. This work highlights the need for a flexible toxicology screening service capable of adapting to changes in drug use such as the growing popularity of legal highs/NPS.

Generation of selectable marker-free transgenic eggplant resistant to Alternaria solani using the R/RS site-specific recombination system.

PubMed

Darwish, Nader Ahmed; Khan, Raham Sher; Ntui, Valentine Otang; Nakamura, Ikuo; Mii, Masahiro

2014-03-01

Marker-free transgenic eggplants, exhibiting enhanced resistance to Alternaria solani , can be generated on plant growth regulators (PGRs)- and antibiotic-free MS medium employing the multi-auto-transformation (MAT) vector, pMAT21 - wasabi defensin , wherein isopentenyl transferase ( ipt ) gene is used as a positive selection marker. Use of the selection marker genes conferring antibiotic or herbicide resistance in transgenic plants has been considered a serious problem for environment and the public. Multi-auto-transformation (MAT) vector system has been one of the tools to excise the selection marker gene and produce marker-free transgenic plants. Ipt gene was used as a selection marker gene. Wasabi defensin gene, isolated from Wasabia japonica (a Japanese horseradish which has been a potential source of antimicrobial proteins), was used as a gene of interest. Wasabi defensin gene was cloned from the binary vector, pEKH-WD, to an ipt-type MAT vector, pMAT21, by gateway cloning technology and transferred to Agrobacterium tumefaciens strain EHA105. Infected cotyledon explants of eggplant were cultured on PGRs- and antibiotic-free MS medium. Extreme shooty phenotype/ipt shoots were produced by the explants infected with the pMAT21-wasabi defensin (WD). The same PGRs- and antibiotic-free MS medium was used in subcultures of the ipt shoots. Subsequently, morphologically normal shoots emerged from the Ipt shoots. Molecular analyses of genomic DNA from transgenic plants confirmed the integration of the WD gene and excision of the selection marker (ipt gene). Expression of the WD gene was confirmed by RT-PCR and Northern blot analyses. In vitro whole plant and detached leaf assay of the marker-free transgenic plants exhibited enhanced resistance against Alternaria solani.

New development and validation of 50 SSR markers in breadfruit (Artocarpus altilis, Moraceae) by next-generation sequencing1

PubMed Central

De Bellis, Fabien; Malapa, Roger; Kagy, Valérie; Lebegin, Stéphane; Billot, Claire; Labouisse, Jean-Pierre

2016-01-01

Premise of the study: Using next-generation sequencing technology, new microsatellite loci were characterized in Artocarpus altilis (Moraceae) and two congeners to increase the number of available markers for genotyping breadfruit cultivars. Methods and Results: A total of 47,607 simple sequence repeat loci were obtained by sequencing a library of breadfruit genomic DNA with an Illumina MiSeq system. Among them, 50 single-locus markers were selected and assessed using 41 samples (39 A. altilis, one A. camansi, and one A. heterophyllus). All loci were polymorphic in A. altilis, 44 in A. camansi, and 21 in A. heterophyllus. The number of alleles per locus ranged from two to 19. Conclusions: The new markers will be useful for assessing the identity and genetic diversity of breadfruit cultivars on a small geographical scale, gaining a better understanding of farmer management practices, and will help to optimize breadfruit genebank management. PMID:27610273

Monte Carlo simulations on marker grouping and ordering.

PubMed

Wu, J; Jenkins, J; Zhu, J; McCarty, J; Watson, C

2003-08-01

Four global algorithms, maximum likelihood (ML), sum of adjacent LOD score (SALOD), sum of adjacent recombinant fractions (SARF) and product of adjacent recombinant fraction (PARF), and one approximation algorithm, seriation (SER), were used to compare the marker ordering efficiencies for correctly given linkage groups based on doubled haploid (DH) populations. The Monte Carlo simulation results indicated the marker ordering powers for the five methods were almost identical. High correlation coefficients were greater than 0.99 between grouping power and ordering power, indicating that all these methods for marker ordering were reliable. Therefore, the main problem for linkage analysis was how to improve the grouping power. Since the SER approach provided the advantage of speed without losing ordering power, this approach was used for detailed simulations. For more generality, multiple linkage groups were employed, and population size, linkage cutoff criterion, marker spacing pattern (even or uneven), and marker spacing distance (close or loose) were considered for obtaining acceptable grouping powers. Simulation results indicated that the grouping power was related to population size, marker spacing distance, and cutoff criterion. Generally, a large population size provided higher grouping power than small population size, and closely linked markers provided higher grouping power than loosely linked markers. The cutoff criterion range for achieving acceptable grouping power and ordering power differed for varying cases; however, combining all situations in this study, a cutoff criterion ranging from 50 cM to 60 cM was recommended for achieving acceptable grouping power and ordering power for different cases.

The genetic map of finger millet, Eleusine coracana.

PubMed

Dida, Mathews M; Srinivasachary; Ramakrishnan, Sujatha; Bennetzen, Jeffrey L; Gale, Mike D; Devos, Katrien M

2007-01-01

Restriction fragment length polymorphism (RFLP), amplified fragment length polymorphism (AFLP), expressed-sequenced tag (EST), and simple sequence repeat (SSR) markers were used to generate a genetic map of the tetraploid finger millet (Eleusine coracana subsp. coracana) genome (2n = 4x = 36). Because levels of variation in finger millet are low, the map was generated in an inter-subspecific F(2) population from a cross between E. coracana subsp. coracana cv. Okhale-1 and its wild progenitor E. coracana subsp. africana acc. MD-20. Duplicated loci were used to identify homoeologous groups. Assignment of linkage groups to the A and B genome was done by comparing the hybridization patterns of probes in Okhale-1, MD-20, and Eleusine indica acc. MD-36. E. indica is the A genome donor to E. coracana. The maps span 721 cM on the A genome and 787 cM on the B genome and cover all 18 finger millet chromosomes, at least partially. To facilitate the use of marker-assisted selection in finger millet, a first set of 82 SSR markers was developed. The SSRs were identified in small-insert genomic libraries generated using methylation-sensitive restriction enzymes. Thirty-one of the SSRs were mapped. Application of the maps and markers in hybridization-based breeding programs will expedite the improvement of finger millet.

Comparative genome-wide polymorphic microsatellite markers in Antarctic penguins through next generation sequencing

PubMed Central

Vianna, Juliana A.; Noll, Daly; Mura-Jornet, Isidora; Valenzuela-Guerra, Paulina; González-Acuña, Daniel; Navarro, Cristell; Loyola, David E.; Dantas, Gisele P. M.

2017-01-01

Abstract Microsatellites are valuable molecular markers for evolutionary and ecological studies. Next generation sequencing is responsible for the increasing number of microsatellites for non-model species. Penguins of the Pygoscelis genus are comprised of three species: Adélie (P. adeliae), Chinstrap (P. antarcticus) and Gentoo penguin (P. papua), all distributed around Antarctica and the sub-Antarctic. The species have been affected differently by climate change, and the use of microsatellite markers will be crucial to monitor population dynamics. We characterized a large set of genome-wide microsatellites and evaluated polymorphisms in all three species. SOLiD reads were generated from the libraries of each species, identifying a large amount of microsatellite loci: 33,677, 35,265 and 42,057 for P. adeliae, P. antarcticus and P. papua, respectively. A large number of dinucleotide (66,139), trinucleotide (29,490) and tetranucleotide (11,849) microsatellites are described. Microsatellite abundance, diversity and orthology were characterized in penguin genomes. We evaluated polymorphisms in 170 tetranucleotide loci, obtaining 34 polymorphic loci in at least one species and 15 polymorphic loci in all three species, which allow to perform comparative studies. Polymorphic markers presented here enable a number of ecological, population, individual identification, parentage and evolutionary studies of Pygoscelis, with potential use in other penguin species. PMID:28898354

A Population Genetics Model of Marker-Assisted Selection

PubMed Central

Luo, Z. W.; Thompson, R.; Woolliams, J. A.

1997-01-01

A deterministic two-loci model was developed to predict genetic response to marker-assisted selection (MAS) in one generation and in multiple generations. Formulas were derived to relate linkage disequilibrium in a population to the proportion of additive genetic variance used by MAS, and in turn to an extra improvement in genetic response over phenotypic selection. Predictions of the response were compared to those predicted by using an infinite-loci model and the factors affecting efficiency of MAS were examined. Theoretical analyses of the present study revealed the nonlinearity between the selection intensity and genetic response in MAS. In addition to the heritability of the trait and the proportion of the marker-associated genetic variance, the frequencies of the selectively favorable alleles at the two loci, one marker and one quantitative trait locus, were found to play an important role in determining both the short- and long-term efficiencies of MAS. The evolution of linkage disequilibrium and thus the genetic response over several generations were predicted theoretically and examined by simulation. MAS dissipated the disequilibrium more quickly than drift alone. In some cases studied, the rate of dissipation was as large as that to be expected in the circumstance where the true recombination fraction was increased by three times and selection was absent. PMID:9215918

Longitudinal study of bone loss in chronic spinal cord injury patients

PubMed Central

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

2015-01-01

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

Speed congenics: accelerated genome recovery using genetic markers.

PubMed

Visscher, P M

1999-08-01

Genetic markers throughout the genome can be used to speed up 'recovery' of the recipient genome in the backcrossing phase of the construction of a congenic strain. The prediction of the genomic proportion during backcrossing depends on the assumptions regarding the distribution of chromosome segments, the population structure, the marker spacing and the selection strategy. In this study simulation was used to investigate the rate of recovery of the recipient genome for a mouse, Drosophila and Arabidopsis genome. It was shown that an incorrect assumption of a binomial distribution of chromosome segments, and failing to take account of a reduction in variance in genomic proportion due to selection, can lead to a downward bias of up to two generations in the estimation of the number of generations required for the formation of a congenic strain.

Developing biochemical and molecular markers for cyanobacterial inoculants.

PubMed

Prasanna, R; Madhan, K; Singh, R N; Chauhan, A K; Nain, L

2010-09-01

Markers for evaluating the establishment of cyanobacteria based on their sensitivity or resistance to antibiotics, saccharide utilization patterns and PCR generated fingerprints were developed. Four selected strains (isolates from rhizosphere soils of diverse agro-ecosystems) have shown potential as diazotrophs and exhibited plant growth promoting abilities. Different responses were obtained on screening against 40 antibiotics, which aided in developing selectable antibiotic markers for each strain. Biochemical profiles generated using standardized chromogenic identification system (including saccharide utilization tests) revealed that 53 % of the saccharides tested were not utilized by any strain, while some strains exhibited unique ability for utilization of saccharides such as melibiose, cellobiose, maltose and glucosamine. PCR based amplification profiles developed using a number of primers based on repeat sequences revealed the utility of 3 primers in providing unique fingerprints for the strains.

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.

Multi-Parametric Spinal Cord MRI as Potential Progression Marker in Amyotrophic Lateral Sclerosis

PubMed Central

El Mendili, Mohamed-Mounir; Cohen-Adad, Julien; Pelegrini-Issac, Mélanie; Rossignol, Serge; Morizot-Koutlidis, Régine; Marchand-Pauvert, Véronique; Iglesias, Caroline; Sangari, Sina; Katz, Rose; Lehericy, Stéphane; Benali, Habib; Pradat, Pierre-François

2014-01-01

Objective To evaluate multimodal MRI of the spinal cord in predicting disease progression and one-year clinical status in amyotrophic lateral sclerosis (ALS) patients. Materials and Methods After a first MRI (MRI1), 29 ALS patients were clinically followed during 12 months; 14/29 patients underwent a second MRI (MRI2) at 11±3 months. Cross-sectional area (CSA) that has been shown to be a marker of lower motor neuron degeneration was measured in cervical and upper thoracic spinal cord from T2-weighted images. Fractional anisotropy (FA), axial/radial/mean diffusivities (λ⊥, λ//, MD) and magnetization transfer ratio (MTR) were measured within the lateral corticospinal tract in the cervical region. Imaging metrics were compared with clinical scales: Revised ALS Functional Rating Scale (ALSFRS-R) and manual muscle testing (MMT) score. Results At MRI1, CSA correlated significantly (P<0.05) with MMT and arm ALSFRS-R scores. FA correlated significantly with leg ALFSRS-R scores. One year after MRI1, CSA predicted (P<0.01) arm ALSFSR-R subscore and FA predicted (P<0.01) leg ALSFRS-R subscore. From MRI1 to MRI2, significant changes (P<0.01) were detected for CSA and MTR. CSA rate of change (i.e. atrophy) highly correlated (P<0.01) with arm ALSFRS-R and arm MMT subscores rate of change. Conclusion Atrophy and DTI metrics predicted ALS disease progression. Cord atrophy was a better biomarker of disease progression than diffusion and MTR. Our study suggests that multimodal MRI could provide surrogate markers of ALS that may help monitoring the effect of disease-modifying drugs. PMID:24755826

Anthropometrics to Identify Overweight Children at Most Risk for the Development of Cardiometabolic Disease.

PubMed

Labyak, Corinne A; Janicke, David M; Lim, Crystal S; Colee, James; Mathews, Anne E

2013-12-01

Sagittal abdominal diameter (SAD) is a novel anthropometric that correlates more strongly with visceral adipose tissue (VAT) and cardiometabolic disease risk in adults compared with body mass index (BMI). However, little research has evaluated this measurement in children. To evaluate SAD as a measure of cardiometabolic risk compared with other anthropometrics in overweight/obese children. This study was a cross-sectional subset analysis of 8- to 12-year-old overweight/ obese children. SAD was compared to BMI, waist circumference (WC), BMI z -score, and percent body fat to determine which measurement was most closely associated with cardiometabolic risk factors. A total cardiometabolic risk score comprising all biochemical markers and blood pressure was also compared to these same anthropometrics. Overweight/obese children (n = 145, mean age 10 ± 1.4 years, mean BMI percentile 97.9 ± 0.02) were included in the analysis. SAD correlated with the greatest number of biochemical markers/blood pressure values including triglycerides ( r = .18, P = .03), HgbA1c ( r = .21, P = .01), and systolic blood pressure ( r = .38, P < .0001). SAD was more strongly correlated to total risk score ( r = .25, P = .002) than WC ( r = .22, P = .006), BMI ( r = .17, P = .04), BMI- z ( r = .18, P = .03), and percent body fat ( r = .18, P = .03). This is the first study to evaluate SAD in overweight/obese American children as a marker of cardiometabolic disease risk. The results suggest a slightly stronger correlation between SAD and cardiometabolic risk factors in overweight/obese children; however, all correlations were weak. As this was a pilot study, additional research is needed prior to recommending the use of this measurement in clinical practice.

Oxidative stress markers imbalance in late-life depression.

PubMed

Diniz, Breno S; Mendes-Silva, Ana Paula; Silva, Lucelia Barroso; Bertola, Laiss; Vieira, Monica Costa; Ferreira, Jessica Diniz; Nicolau, Mariana; Bristot, Giovana; da Rosa, Eduarda Dias; Teixeira, Antonio L; Kapczinski, Flavio

2018-03-20

Oxidative stress has been implicated in the pathophysiology of mood disorders in young adults. However, there is few data to support its role in the elderly. The primary aim of this study was to evaluate whether subjects with late-life depression (LLD) presented with changes in oxidative stress response in comparison with the non-depressed control group. We then explored how oxidative stress markers associated with specific features of LLD, in particular cognitive performance and age of onset of major depressive disorder in these individuals. We included a convenience sample of 124 individuals, 77 with LLD and 47 non-depressed subjects (Controls). We measure the plasma levels of 6 oxidative stress markers: thiobarbituric acid reactive substances (TBARS), protein carbonil content (PCC), free 8-isoprostane, glutathione peroxidase (GPx) activity, glutathione reductase (GR) activity, and glutathione S-transferase (GST) activity. We found that participants with LLD had significantly higher free 8-isoprostane levels (p = 0.003) and lower glutathione peroxidase activity (p = 0.006) compared to controls. Free 8-isoprostane levels were also significantly correlated with worse scores in the initiation/perseverance (r = -0.24, p = 0.01), conceptualization (r = -0.22, p = 0.02) sub-scores, and the total scores (r = -0.21, p = 0.04) on the DRS. Our study provides robust evidence of the imbalance between oxidative stress damage, in particular lipid peroxidation, and anti-oxidative defenses as a mechanism related to LLD, and cognitive impairment in this population. Interventions aiming to reduce oxidative stress damage can have a potential neuroprotective effect for LLD subjects. Copyright © 2018 Elsevier Ltd. All rights reserved.

Dexamethasone, Intravenous Immunoglobulin, and Rituximab Combination Immunotherapy for Pediatric Opsoclonus-Myoclonus Syndrome.

PubMed

Pranzatelli, Michael R; Tate, Elizabeth D

2017-08-01

Although pulse-dose dexamethasone is increasingly favored for treating pediatric opsoclonus-myoclonus syndrome (OMS), and multimodal immunotherapy is associated with improved clinical response, there have been no neuroimmunologic studies of dexamethasone-based multimodal disease-modifying therapy. In this observational retrospective study, 19 children with OMS (with or without associated neuroblastoma) underwent multibiomarker evaluation for neuroinflammation. Nine children of varying OMS severity, duration, and treatment status were treated empirically with pulse dexamethasone, intravenous immunoglobulin (IVIg), and rituximab combination immunotherapy (DEXIR-CI). Another 10 children on dexamethasone alone or with IVIg at initial evaluation only provided a comparison group. Motor severity (total score) was scored rater-blinded via videotapes using the validated OMS Evaluation Scale. DEXIR-CI was associated with a 69% reduction in group total score (P = 0.004) and was clinically well tolerated. Patients given the dexamethasone combination exhibited significantly lowered B cell frequencies in cerebrospinal fluid (-94%) and blood (-76%), normalizing the cerebrospinal fluid B cell percentage. The number of patients with positive inflammatory markers dropped 87% (P = 0.002) as did the number of markers. Cerebrospinal fluid oligoclonal bands were positive in four of nine pretreatment patients but zero of six post-treatment patients. In the comparison group, partial response to dexamethasone alone or with IVIg was associated with multiple positive markers for neuroinflammation despite an average of seven months of treatment. Multimechanistic dexamethasone-based combination immunotherapy increases the therapeutic armamentarium for OMS, providing a viable option for less severely affected individuals. Partial response to dexamethasone with or without IVIg is indicative of ongoing neuroinflammation and should be treated promptly and accordingly. Copyright © 2017 Elsevier Inc. All rights reserved.

Non-invasive assessment of liver fibrosis progression in hepatitis C patients retreated for 96 weeks with antiviral therapy: a randomized study.

PubMed

Zarski, Jean-Pierre; Sturm, Nathalie; Desmorat, Hervé; Melin, Pascal; Raabe, Jean-Jacques; Bonny, Corinne; Sogni, Philippe; Pinta, Alexandrina; Rouanet, Stéphanie; Babany, Gérard; Cheveau, Alice; Chevallier, Michèle

2010-08-01

The efficacy of a maintenance therapy in non-responder patients with chronic hepatitis C has been essentially evaluated by histological semiquantitative scores. The aim was to evaluate the efficiency of 2 years of treatment with peginterferon alpha-2a vs alpha-tocopherol in these patients by histology, morphometry and blood markers of fibrosis. Hundred and five HCV patients with a Metavir fibrosis score > or = 2 were randomized to receive peginterferon alpha-2a 180 microg/week (PEG) (n=55) or alpha-tocopherol (TOCO) 1000 mg/day (n=50) for 96 weeks. The primary endpoint was improvement or stabilization of the Metavir fibrosis score by biopsy performed at week 96. Secondary endpoints included a quantitative assessment of fibrosis by morphometry and changes in blood markers of fibrosis. There was no difference at baseline between PEG and TOCO according to the metavir (83.3 vs 86.8%, P=0.751) stage. The median fibrosis rate, measured with morphometry was 2.72 and 2.86% at day 0, and 3.66 and 2.82% at week 96, in the PEG and TOCO groups (P=0.90) respectively. However, the percentage of patients with metavir activity grade improvement was significantly higher in the PEG group vs the TOCO group (52.8 vs 23.7%, P=0.016). Non-invasive markers analysis did not show any significant change in both groups. Long-term therapy with peginterferon alpha-2a did not reduce liver fibrosis degree assessed by morphometry and blood tests as compared with alpha-tocopherol. Blood tests could be useful to assess liver fibrosis changes in clinical trials.

Urinary Proteomic Biomarkers for Diagnosis and Risk Stratification of Autosomal Dominant Polycystic Kidney Disease: A Multicentric Study

PubMed Central

Kistler, Andreas D.; Serra, Andreas L.; Siwy, Justyna; Poster, Diane; Krauer, Fabienne; Torres, Vicente E.; Mrug, Michal; Grantham, Jared J.; Bae, Kyongtae T.; Bost, James E.; Mullen, William; Wüthrich, Rudolf P.; Mischak, Harald; Chapman, Arlene B.

2013-01-01

Treatment options for autosomal dominant polycystic kidney disease (ADPKD) will likely become available in the near future, hence reliable diagnostic and prognostic biomarkers for the disease are strongly needed. Here, we aimed to define urinary proteomic patterns in ADPKD patients, which aid diagnosis and risk stratification. By capillary electrophoresis online coupled to mass spectrometry (CE-MS), we compared the urinary peptidome of 41 ADPKD patients to 189 healthy controls and identified 657 peptides with significantly altered excretion, of which 209 could be sequenced using tandem mass spectrometry. A support-vector-machine based diagnostic biomarker model based on the 142 most consistent peptide markers achieved a diagnostic sensitivity of 84.5% and specificity of 94.2% in an independent validation cohort, consisting of 251 ADPKD patients from five different centers and 86 healthy controls. The proteomic alterations in ADPKD included, but were not limited to markers previously associated with acute kidney injury (AKI). The diagnostic biomarker model was highly specific for ADPKD when tested in a cohort consisting of 481 patients with a variety of renal and extrarenal diseases, including AKI. Similar to ultrasound, sensitivity and specificity of the diagnostic score depended on patient age and genotype. We were furthermore able to identify biomarkers for disease severity and progression. A proteomic severity score was developed to predict height adjusted total kidney volume (htTKV) based on proteomic analysis of 134 ADPKD patients and showed a correlation of r = 0.415 (p<0.0001) with htTKV in an independent validation cohort consisting of 158 ADPKD patients. In conclusion, the performance of peptidomic biomarker scores is superior to any other biochemical markers of ADPKD and the proteomic biomarker patterns are a promising tool for prognostic evaluation of ADPKD. PMID:23326375

Proposal of a Video-recording System for the Assessment of Bell's Palsy: Methodology and Preliminary Results.

PubMed

Monini, Simonetta; Marinozzi, Franco; Atturo, Francesca; Bini, Fabiano; Marchelletta, Silvia; Barbara, Maurizio

2017-09-01

To propose a new objective video-recording procedure to assess and monitor over time the severity of facial nerve palsy. No objective methods for facial palsy (FP) assessment are universally accepted. The face of subjects presenting with different degrees of facial nerve deficit, as measured by the House-Brackmann (HB) grading system, was videotaped after positioning, at specific points, 10 gray circular markers made of a retroreflective material. Video-recording included the resting position and six ordered facial movements. Editing and data elaboration was performed using a software instructed to assess marker distances. From the differences of the marker distances between the two sides was then extracted a score. The higher the FP degree, the higher the score registered during each movement. The statistical significance differed during the various movements between the different FP degrees, being uniform when closing the eyes gently; whereas when wrinkling the nose, there was no difference between the HB grade III and IV groups and, when smiling, no difference was evidenced between the HB grade IV and V groups.The global range index, which represents the overall degree of FP, was between 6.2 and 7.9 in the normal subjects (HB grade I); between 10.6 and 18.91 in HB grade II; between 22.19 and 33.06 in HB grade III; between 38.61 and 49.75 in HB grade IV; and between 50.97 and 66.88 in HB grade V. The proposed objective methodology could provide numerical data that correspond to the different degrees of FP, as assessed by the subjective HB grading system. These data can in addition be used singularly to score selected areas of the paralyzed face when recovery occurs with a different timing in the different face regions.

Associations between maternal experiences of racism and early child health and development: findings from the UK Millennium Cohort Study.

PubMed

Kelly, Yvonne; Becares, Laia; Nazroo, James

2013-01-01

Emerging evidence suggests that experienced racism might help explain observed ethnic inequalities in early child health and development. There are few studies outside the US context and none that consider mothers' experiences of racism in relation to a range of early childhood health and developmental markers. The authors used cross-sectional data from the UK Millennium Cohort Study on 2136 mothers and their 5-year-old children from ethnic minority groups. Measures of racism tapped two dimensions of mothers' experience: perceived frequency of racist attacks in residential area and interpersonal racism. Markers of child health and development were obesity; socioemotional difficulties; cognitive: verbal, non-verbal and spatial ability test scores. There was a suggestion that the mothers' experience of interpersonal racism was associated with an increased risk of obesity ('received insults' OR=1.47; 'treated unfairly' OR=1.57; 'disrespectful treatment by shop staff' OR=1.55), but all CIs crossed 1.0, and size estimates were attenuated on further statistical adjustment. Perception of racism in the residential area was associated with socioemotional difficulties (fully adjusted coefficient=1.40, SE=0.47) and spatial abilities (fully adjusted coefficient=-1.99, SE=0.93) but not with verbal or non-verbal ability scores. Maternal experiences of racist insults were associated with non-verbal ability scores (fully adjusted coefficient=-1.70, SE=0.88). The results suggest that mothers' experienced racism is linked to markers of early child health and development. Interventions that aim to improve early child development and address ethnic health inequalities need to incorporate approaches to tackling racism at all levels of society.

Clinical significance of nailfold capillaroscopy in systemic lupus erythematosus: correlation with endothelial cell activation markers and disease activity.

PubMed

Kuryliszyn-Moskal, A; Ciolkiewicz, M; Klimiuk, P A; Sierakowski, S

2009-01-01

To evaluate whether nailfold capillaroscopy (NC) changes are associated with the main serum endothelial cell activation markers and the disease activity of systemic lupus erythematosus (SLE). Serum levels of vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), soluble E-selectin (sE-selectin), and soluble thrombomodulin (sTM) were determined by an enzyme-linked immunosorbent assay (ELISA) in 80 SLE patients and 33 healthy controls. Nailfold capillary abnormalities were seen in 74 out of 80 (92.5%) SLE patients. A normal capillaroscopic pattern or mild changes were found in 33 (41.25%) and moderate/severe abnormalities in 47 (58.75%) of all SLE patients. In SLE patients a capillaroscopic score >1 was more frequently associated with the presence of internal organ involvement (p < 0.001) as well as with immunosuppressive therapy (p < 0.01). Significant differences were found in VEGF (p < 0.001), ET-1 (p < 0.001), sE-selectin (p < 0.01), and sTM (p < 0.001) serum concentrations between SLE patients with a capillaroscopic score > 1 and controls. SLE patients with severe/moderate capillaroscopic abnormalities showed significantly higher VEGF serum levels than patients with mild changes (p < 0.001). Moreover, there was a significant positive correlation between the severity of capillaroscopic changes and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (p < 0.005) as well as between capillaroscopic score and VEGF serum levels (p < 0.001). Our findings confirm the usefulness of NC as a non-invasive technique for the evaluation of microvascular involvement in SLE patients. A relationship between changes in NC, endothelial cell activation markers and clinical features of SLE suggest an important role for microvascular abnormalities in clinical manifestation of the disease.

Prediction of clinical infection in women with preterm labour with intact membranes: a score based on ultrasonographic, clinical and biological markers.

PubMed

Kayem, Gilles; Maillard, Françoise; Schmitz, Thomas; Jarreau, Pierre H; Cabrol, Dominique; Breart, Gérard; Goffinet, François

2009-07-01

To predict maternal and neonatal clinical infection at admission in women hospitalized for preterm labour (PTL) with intact membranes. Prospective study of 371 women hospitalized for preterm labour with intact membranes. The primary outcome was clinical infection, defined by clinical chorioamnionitis at delivery or early-onset neonatal infection. Clinical infection was identified in 21 cases (5.7%) and was associated with earlier gestational age at admission for PTL, elevated maternal C-reactive protein (CRP) and white blood cell count (WBC), shorter cervical length, and a cervical funnelling on ultrasound. We used ROC curves to determine the cut-off values that minimized the number of false positives and false negatives. The cut-off points chosen were 30 weeks for gestational age at admission, 25 mm for cervical length, 8 mg/l for CRP and 12,000 c/mm(3) for WBC. Each of these variables was assigned a weight on the basis of the adjusted odds ratios in a clinical infection risk score (CIRS). We set a threshold corresponding to a specificity close to 90%, and calculated the positive and negative predictive values and likelihood ratios of each marker and of the CIRS. The CIRS had a sensitivity of 61.9%, while the sensitivity of the other markers ranged from 19.0% to 42.9%. Internal cross-validation was used to estimate the performance of the CIRS in new subjects. The diagnostic values found remained close to the initial values. A clinical infection risk score built from data known at admission for preterm labour helps to identify women and newborns at high risk of clinical infection.

[Association of Schizophrenia and its Clinical Implications with the NOS1AP Gene in the Colombian Population].

PubMed

Valencia, Jenny García; Duarte, Ana Victoria Valencia; Vila, Ana Lucía Páez; Kremeyer, Bárbara; Montoya, María Patricia Arbeláez; Linares, Andrés Ruiz; Acosta, Carlos Alberto Palacio; Duque, Jorge Ospina; Berrío, Gabriel Bedoya

2012-06-01

The nitric oxide synthase 1 adaptor protein (NOS1AP) gene is possibly implicated in schizophrenia etiopathogenesis. To determine the association of NOS1AP gene variants with schizophrenia and the relationship of variants with the clinical dimensions of the disorder in the Colombian population. It is a case-control study with 255 subjects per group. Markers within the NOS1AP gene were typified as well as other informative material of genetic origin so as to adjust by population stratification. A factorial analysis of the main components for each item in the Scales for Evaluating Negative Symptoms (SENS) together with the Scales for Evaluating Positive Symptoms (SEPS) to determine clinical dimensions. Association between the C/C genotype of the rs945713 marker with schizophrenia (OR = 1.79, 95% CI: 1.13 - 2.84) was found. The C/C genotype of the rs945713 was related to higher scores in the "affective flattening and alogia" dimension; and the A/A genotype of the rs4657181 marker was associated to lower scores in the same dimension. Significant associations of markers inside the NOS1AP gene with schizophrenia and the "affective flattening and alogia" clinical dimension were found. These results are consistent with previous studies and support the possibility that NOS1AP influences schizophrenia susceptibility. Furthermore, NOS1AP might be a modifier of schizophrenia clinical characteristics. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Prognostic relevance of proliferation markers (Ki-67, PHH3) within the cross-relation of ERG translocation and androgen receptor expression in prostate cancer.

PubMed

Goltz, Diane; Montani, Matteo; Braun, Martin; Perner, Sven; Wernert, Nicolas; Jung, Klaus; Dietel, Manfred; Stephan, Carsten; Kristiansen, Glen

2015-12-01

We evaluated the prognostic value of the mitosis-associated marker phosphorylated histone H3 (PHH3) and Ki-67 in prostate cancer with respect to ERG status and androgen receptor (AR) expression.PHH3 and Ki-67 expression was immunohistochemically detected and digitally quantitated in a radical prostatectomy cohort (n = 640). The results were correlated to clinicopathological parameters including biochemical recurrence times. Prognostic values of PHH3 and Ki-67 were analysed by Cox regression and Kaplan-Meier statistics.In prostate cancer, mean Ki-67 and PHH3 rates were 3.40% (95%CI 3.16-3.63%) and 0.0152% (95%CI 0.0112-0.0191%), respectively.Ki-67 showed a significant correlation with Gleason scores, pT status, margin status, and AR expression, while PHH3 showed a significant correlation with Gleason scores and pT status. Univariate analyses for biochemical recurrence times demonstrated a significant prognostic value for median Ki-67 rate and for the PHH3 rate of the 90th percentile. Of importance, in patient subgroups stratified according to AR expression and ERG translocation, the prognostic power of proliferation markers PHH3 and Ki-67 was markedly enhanced in ERG translocation negative and high-level AR expressing ERG translocation positive prostate cancers.As expected, the proliferation markers PHH3 and Ki-67 predict adverse outcome of prostate cancer and have a particularly pronounced prognostic value in specific molecular subsets of prostate cancer (ERG- or AR+).

Evaluation of Accessory Lacrimal Gland in Muller’s Muscle Conjunctival Resection Specimens for Precursor Cell Markers and Biological Markers of Dry Eye Disease

PubMed Central

Ali, Marwan; Shah, Dhara; Pasha, Zeeshan; Jassim, Sarmad H.; Jaboori, Assraa Jassim; Setabutr, Pete; Aakalu, Vinay K.

2017-01-01

Purpose The accessory lacrimal glands (ALG) are an understudied component of the tear functional unit, even though they are important in the development of dry eye syndrome (DES). To advance our understanding of aging changes, regenerative potential and histologic correlates to human characteristics, we investigated human ALG tissue from surgical samples to determine the presence or absence of progenitor cell markers and lacrimal epithelial markers and to correlate marker expression to relevant patient characteristics. Materials and Methods ALG tissues obtained from Muller’s Muscle Conjunctival Resection (MMCR) specimens were created using tissue microarrays (TMAs). Immunofluorescence staining of MMCR sections was performed using primary antibodies specific to cell protein markers. Cell marker localization in TMAs was then assessed by two blinded observers using a standardized scoring system. Patient characteristics including age, race, and status of ocular surface health were then compared against expression of stem cell markers. Results Human ALG expressed a number of epithelial markers, and in particular, histatin-1 was well correlated with the expression of epithelial markers and was present in most acini. In addition, we noted the presence of precursor cell markers nestin, ABCG2 and CD90 in ALG tissue. There was a decrease in precursor cell marker expression with increasing age. Finally, we noted that a negative association was present between histatin-1 expression and DES. Conclusions Thus, we report for the first time that human ALG tissues contain precursor marker positive cells and that this marker expression may decrease with increasing age. Moreover, histatin-1 expression may be decreased in DES. Future studies will be performed to use these cell markers to isolate and culture lacrimal epithelial cells from heterogeneous tissues, determine the relevance of histatin-1 expression to DES and isolate candidate precursor cells from ALG tissue. PMID:27612554

Fast and Accurate Construction of Ultra-Dense Consensus Genetic Maps Using Evolution Strategy Optimization

PubMed Central

Mester, David; Ronin, Yefim; Schnable, Patrick; Aluru, Srinivas; Korol, Abraham

2015-01-01

Our aim was to develop a fast and accurate algorithm for constructing consensus genetic maps for chip-based SNP genotyping data with a high proportion of shared markers between mapping populations. Chip-based genotyping of SNP markers allows producing high-density genetic maps with a relatively standardized set of marker loci for different mapping populations. The availability of a standard high-throughput mapping platform simplifies consensus analysis by ignoring unique markers at the stage of consensus mapping thereby reducing mathematical complicity of the problem and in turn analyzing bigger size mapping data using global optimization criteria instead of local ones. Our three-phase analytical scheme includes automatic selection of ~100-300 of the most informative (resolvable by recombination) markers per linkage group, building a stable skeletal marker order for each data set and its verification using jackknife re-sampling, and consensus mapping analysis based on global optimization criterion. A novel Evolution Strategy optimization algorithm with a global optimization criterion presented in this paper is able to generate high quality, ultra-dense consensus maps, with many thousands of markers per genome. This algorithm utilizes "potentially good orders" in the initial solution and in the new mutation procedures that generate trial solutions, enabling to obtain a consensus order in reasonable time. The developed algorithm, tested on a wide range of simulated data and real world data (Arabidopsis), outperformed two tested state-of-the-art algorithms by mapping accuracy and computation time. PMID:25867943

Accuracy of Genomic Prediction in Switchgrass (Panicum virgatum L.) Improved by Accounting for Linkage Disequilibrium

PubMed Central

Ramstein, Guillaume P.; Evans, Joseph; Kaeppler, Shawn M.; Mitchell, Robert B.; Vogel, Kenneth P.; Buell, C. Robin; Casler, Michael D.

2016-01-01

Switchgrass is a relatively high-yielding and environmentally sustainable biomass crop, but further genetic gains in biomass yield must be achieved to make it an economically viable bioenergy feedstock. Genomic selection (GS) is an attractive technology to generate rapid genetic gains in switchgrass, and meet the goals of a substantial displacement of petroleum use with biofuels in the near future. In this study, we empirically assessed prediction procedures for genomic selection in two different populations, consisting of 137 and 110 half-sib families of switchgrass, tested in two locations in the United States for three agronomic traits: dry matter yield, plant height, and heading date. Marker data were produced for the families’ parents by exome capture sequencing, generating up to 141,030 polymorphic markers with available genomic-location and annotation information. We evaluated prediction procedures that varied not only by learning schemes and prediction models, but also by the way the data were preprocessed to account for redundancy in marker information. More complex genomic prediction procedures were generally not significantly more accurate than the simplest procedure, likely due to limited population sizes. Nevertheless, a highly significant gain in prediction accuracy was achieved by transforming the marker data through a marker correlation matrix. Our results suggest that marker-data transformations and, more generally, the account of linkage disequilibrium among markers, offer valuable opportunities for improving prediction procedures in GS. Some of the achieved prediction accuracies should motivate implementation of GS in switchgrass breeding programs. PMID:26869619

CONSTRAINTS ON VARIABLES IN SYNTAX.

ERIC Educational Resources Information Center

ROSS, JOHN ROBERT

IN ATTEMPTING TO DEFINE "SYNTACTIC VARIABLE," THE AUTHOR BASES HIS DISCUSSION ON THE ASSUMPTION THAT SYNTACTIC FACTS ARE A COLLECTION OF TWO TYPES OF RULES--CONTEXT-FREE PHRASE STRUCTURE RULES (GENERATING UNDERLYING OR DEEP PHRASE MARKERS) AND GRAMMATICAL TRANSFORMATIONS, WHICH MAP UNDERLYING PHRASE MARKERS ONTO SUPERFICIAL (OR SURFACE) PHRASE…

Analysis of facial motion patterns during speech using a matrix factorization algorithm

PubMed Central

Lucero, Jorge C.; Munhall, Kevin G.

2008-01-01

This paper presents an analysis of facial motion during speech to identify linearly independent kinematic regions. The data consists of three-dimensional displacement records of a set of markers located on a subject’s face while producing speech. A QR factorization with column pivoting algorithm selects a subset of markers with independent motion patterns. The subset is used as a basis to fit the motion of the other facial markers, which determines facial regions of influence of each of the linearly independent markers. Those regions constitute kinematic “eigenregions” whose combined motion produces the total motion of the face. Facial animations may be generated by driving the independent markers with collected displacement records. PMID:19062866

CORK Study in Cystic Fibrosis: Sustained Improvements in Ultra-Low-Dose Chest CT Scores After CFTR Modulation With Ivacaftor.

PubMed

Ronan, Nicola J; Einarsson, Gisli G; Twomey, Maria; Mooney, Denver; Mullane, David; NiChroinin, Muireann; O'Callaghan, Grace; Shanahan, Fergus; Murphy, Desmond M; O'Connor, Owen J; Shortt, Cathy A; Tunney, Michael M; Eustace, Joseph A; Maher, Michael M; Elborn, J Stuart; Plant, Barry J

2018-02-01

Ivacaftor produces significant clinical benefit in patients with cystic fibrosis (CF) with the G551D mutation. Prevalence of this mutation at the Cork CF Centre is 23%. This study assessed the impact of cystic fibrosis transmembrane conductance regulator modulation on multiple modalities of patient assessment. Thirty-three patients with the G551D mutation were assessed at baseline and prospectively every 3 months for 1 year after initiation of ivacaftor. Change in ultra-low-dose chest CT scans, blood inflammatory mediators, and the sputum microbiome were assessed. Significant improvements in FEV 1 , BMI, and sweat chloride levels were observed post-ivacaftor treatment. Improvement in ultra-low-dose CT imaging scores were observed after treatment, with significant mean reductions in total Bhalla score (P < .01), peribronchial thickening (P = .035), and extent of mucous plugging (P < .001). Reductions in circulating inflammatory markers, including interleukin (IL)-1β, IL-6, and IL-8 were demonstrated. There was a 30% reduction in the relative abundance of Pseudomonas species and an increase in the relative abundance of bacteria associated with more stable community structures. Posttreatment community richness increased significantly (P = .03). Early and sustained improvements on ultra-low-dose CT scores suggest it may be a useful method of evaluating treatment response. It paralleled improvement in symptoms, circulating inflammatory markers, and changes in the lung microbiota. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

D-dimer as marker for microcirculatory failure: correlation with LOD and APACHE II scores.

PubMed

Angstwurm, Matthias W A; Reininger, Armin J; Spannagl, Michael

2004-01-01

The relevance of plasma d-dimer levels as marker for morbidity and organ dysfunction in severely ill patients is largely unknown. In a prospective study we determined d-dimer plasma levels of 800 unselected patients at admission to our intensive care unit. In 91% of the patients' samples d-dimer levels were elevated, in some patients up to several hundredfold as compared to normal values. The highest mean d-dimer values were present in the patient group with thromboembolic diseases, and particularly in non-survivors of pulmonary embolism. In patients with circulatory impairment (r=0.794) and in patients with infections (r=0.487) a statistically significant correlation was present between d-dimer levels and the APACHE II score (P<0.001). The logistic organ dysfunction score (LOD, P<0.001) correlated with d-dimer levels only in patients with circulatory impairment (r=0.474). On the contrary, patients without circulatory impairment demonstrated no correlation of d-dimer levels to the APACHE II or LOD score. Taking all patients together, no correlations of d-dimer levels with single organ failure or with indicators of infection could be detected. In conclusion, d-dimer plasma levels strongly correlated with the severity of the disease and organ dysfunction in patients with circulatory impairment or infections suggesting that elevated d-dimer levels may reflect the extent of microcirculatory failure. Thus, a therapeutic strategy to improve the microcirculation in such patients may be monitored using d-dimer plasma levels.

Twenty-four-hour packed red blood cell requirement is the strongest independent prognostic marker of mortality in ED trauma patients.

PubMed

Arslan, Albert; Flax, Lindsey; Fraser, Robert; Kanter, Marc; Simon, Ronald; Caputo, Nicholas D

2016-06-01

Injury severity score, serum lactate, and shock index help the physician determine the severity of injuries present and have been shown to relate to mortality. We sought to determine if an increasing amount of packed red blood cells (PRBCs) given in the first 24hours of admission is an independent predictor of mortality and how it compares to other validated markers. A 6-year retrospective, observational study of adult trauma patients was conducted at a level 1 trauma center. Charts were reviewed for demographic data, amount of PRBC received in the first 24hours, injury severity score, shock index, and lactate levels. Subgroups were used to determine if each variable was an independent predictor of mortality. Correlation coefficients and linear regression were used to determine the strength of correlation between each variable and mortality. One hundred fifty-seven patients met criteria over a 6-year period. The average age was 28years, 93% were male, and 86% had penetrating injuries. The average injury severity score, serum lactate, and shock index were 18, 6.1, and 0.9, respectively. The average amount of blood given was 6.7 U. Twenty-four-hour PRBC requirement is both a novel independent predictor of and has the greatest correlation to mortality in adult trauma patients when compared to injury severity score, shock index, and serum lactate. Copyright © 2016 Elsevier Inc. All rights reserved.