The Relationship between the UniProt Knowledgebase (UniProtKB) and the IntAct Molecular Interaction Databases

IntAct provides a freely available, open source database system and analysis tools for protein interaction data. All interactions are derived from literature curation or direct user submission and all experimental information relating to binary protein-protein
interactions is entered into the IntAct database by curators, via a web-based editor. Interaction information is added to the SUBUNIT comment and the RP line of the relevant publication within the UniProtKB entry. There may be a single INTERACTION comment present within a UniProtKB entry, which conveys information relevant to binary protein-protein interactions. This is automatically derived from the IntAct database and is updated on a triweekly basis. Interactions can be derived by any appropriate experimental method but must be confirmed by a second interaction if resulting from a single yeast2hybrid experiment. For large-scale experiments, interactions are considered if a high confidence score is assigned by the authors. The INTERACTION line contains a direct link to IntAct that provides detailed information for the experimental support. These lines are not changed manually and any discrepancy is reported to IntAct for updates. There is also a database crossreference line within the UniProtKB entry i.e.: DR IntAct _UniProtKB AC, which directs the user to additional interaction data for that molecule. 
UniProt is supported by grants from the National Institutes of Health, European Commission, Swiss Federal Government and PATRIC BRC.
IntAct is funded by the European Commission under FELICS, contract number 021902 (RII3) within the Research Infrastructure Action of the FP6 "Structuring the European Research Area" Programme

Expenditure, Coping, and Academic Behaviors Among Food-Insecure College Students at 10 Higher Education Institutes in the Appalachian and Southeastern Regions

Background A number of studies have measured college student food insecurity prevalence higher than the national average; however, no multicampus regional study among students at 4-y institutions has been undertaken in the Appalachian and Southeast regions of the United States. Objectives The aims of this study were to determine the prevalence of food insecurity among college students in the Appalachian and Southeastern regions of the United States, and to determine the association between food-insecurity status and money expenditures, coping strategies, and academic performance among a regional sample of college students. Methods This regional, cross-sectional, online survey study included 13,642 college students at 10 public universities. Food-insecurity status was measured through the use of the USDA Adult Food Security Survey. The outcomes were associations between food insecurity and behaviors determined with the use of the money expenditure scale (MES), the coping strategy scale (CSS), and the academic progress scale (APS). A forward-selection logistic regression model was used with all variables significant from individual Pearson chi-square and Wilcoxon analyses. The significance criterion α for all tests was 0.05. Results The prevalence of food insecurity at the universities ranged from 22.4% to 51.8% with an average prevalence of 30.5% for the full sample. From the forward-selection logistic regression model, MES (OR: 1.47; 95% CI: 1.40, 1.55), CSS (OR: 1.19; 95% CI: 1.18, 1.21), and APS (OR: 0.95; 95% CI: 0.91, 0.99) scores remained significant predictors of food insecurity. Grade point average, academic year, health, race/ethnicity, financial aid, cooking frequency, and health insurance also remained significant predictors of food security status. Conclusions Food insecurity prevalence was higher than the national average. Food-insecure college students were more likely to display high money expenditures and exhibit coping behaviors, and to have poor academic performance

Expenditure, Coping, and Academic Behaviors Among Food-Insecure College Students at 10 Higher Education Institutes in the Appalachian and Southeastern Regions

Background A number of studies have measured college student food insecurity prevalence higher than the national average; however, no multicampus regional study among students at 4-y institutions has been undertaken in the Appalachian and Southeast regions of the United States. Objectives The aims of this study were to determine the prevalence of food insecurity among college students in the Appalachian and Southeastern regions of the United States, and to determine the association between food-insecurity status and money expenditures, coping strategies, and academic performance among a regional sample of college students. Methods This regional, cross-sectional, online survey study included 13,642 college students at 10 public universities. Food-insecurity status was measured through the use of the USDA Adult Food Security Survey. The outcomes were associations between food insecurity and behaviors determined with the use of the money expenditure scale (MES), the coping strategy scale (CSS), and the academic progress scale (APS). A forward-selection logistic regression model was used with all variables significant from individual Pearson chi-square and Wilcoxon analyses. The significance criterion α for all tests was 0.05. Results The prevalence of food insecurity at the universities ranged from 22.4% to 51.8% with an average prevalence of 30.5% for the full sample. From the forward-selection logistic regression model, MES (OR: 1.47; 95% CI: 1.40, 1.55), CSS (OR: 1.19; 95% CI: 1.18, 1.21), and APS (OR: 0.95; 95% CI: 0.91, 0.99) scores remained significant predictors of food insecurity. Grade point average, academic year, health, race/ethnicity, financial aid, cooking frequency, and health insurance also remained significant predictors of food security status. Conclusions Food insecurity prevalence was higher than the national average. Food-insecure college students were more likely to display high money expenditures and exhibit coping behaviors, and to have poor academic performance

CANDELS Observations of the Environmental Dependence of the Color-Mass-Morphology Relation at z = 1.6

We study the environmental dependence of color, stellar mass, and morphology by comparing galaxies in a forming cluster to those in the field at z = 1:6 with Hubble Space Telescope near-infrared imaging in the CANDELS/UDS field. We quantify the morphology of the galaxies using the effective radius, reff, and S\'ersic index, n. In both the cluster and field, approximately half of the bulge-dominated galaxies (n > 2) reside on the red sequence of the color-magnitude diagram, and most disk-dominated galaxies (n < 2) have colors expected for star-forming galaxies. There is weak evidence that cluster galaxies have redder rest-frame U - B colors and higher stellar masses compared to the field. Star-forming galaxies in both the cluster and field show no significant differences in their morphologies. In contrast, there is evidence that quiescent galaxies in the cluster have larger median effective radii and smaller S\'ersic indices compared to the field with a significance of 2?. These differences are most pronounced for galaxies at clustercentric distances 1 Mpc < Rproj < 1.5 Mpc, which have low S\'ersic indices and possibly larger effective radii, more consistent with star-forming galaxies at this epoch and in contrast to other quiescent galaxies. We argue that star-forming galaxies are processed under the influence of the cluster environment at distances greater than the cluster-halo virial radius. Our results are consistent with models where gas accretion onto these galaxies is suppressed from processes associated with the cluster environment.Comment: ApJ accepted, 19 pages, 10 figure

Conference on Best Practices for Managing \u3cem\u3eDaubert\u3c/em\u3e Questions

This article is a transcript of the Philip D. Reed Lecture Series Conference on Best Practices for Managing Daubert Questions, held on October 25, 2019, at Vanderbilt Law School under the sponsorship of the Judicial Conference Advisory Committee on Evidence Rules. The transcript has been lightly edited and represents the panelists’ individual views only and in no way reflects those of their affiliated firms, organizations, law schools, or the judiciary

Whole-Genome Sequencing of a Single Proband Together with Linkage Analysis Identifies a Mendelian Disease Gene

Although more than 2,400 genes have been shown to contain variants that cause Mendelian disease, there are still several thousand such diseases yet to be molecularly defined. The ability of new whole-genome sequencing technologies to rapidly indentify most of the genetic variants in any given genome opens an exciting opportunity to identify these disease genes. Here we sequenced the whole genome of a single patient with the dominant Mendelian disease, metachondromatosis (OMIM 156250), and used partial linkage data from her small family to focus our search for the responsible variant. In the proband, we identified an 11 bp deletion in exon four of PTPN11, which alters frame, results in premature translation termination, and co-segregates with the phenotype. In a second metachondromatosis family, we confirmed our result by identifying a nonsense mutation in exon 4 of PTPN11 that also co-segregates with the phenotype. Sequencing PTPN11 exon 4 in 469 controls showed no such protein truncating variants, supporting the pathogenicity of these two mutations. This combination of a new technology and a classical genetic approach provides a powerful strategy to discover the genes responsible for unexplained Mendelian disorders

Predictors of linkage to care following community-based HIV counseling and testing in rural Kenya

Despite innovations in HIV counseling and testing (HCT), important gaps remain in understanding linkage to care. We followed a cohort diagnosed with HIV through a community-based HCT campaign that trained persons living with HIV/AIDS (PLHA) as navigators. Individual, interpersonal, and institutional predictors of linkage were assessed using survival analysis of self-reported time to enrollment. Of 483 persons consenting to follow-up, 305 (63.2%) enrolled in HIV care within 3 months. Proportions linking to care were similar across sexes, barring a sub-sample of men aged 18–25 years who were highly unlikely to enroll. Men were more likely to enroll if they had disclosed to their spouse, and women if they had disclosed to family. Women who anticipated violence or relationship breakup were less likely to link to care. Enrolment rates were significantly higher among participants receiving a PLHA visit, suggesting that a navigator approach may improve linkage from community-based HCT campaigns.Vestergaard Frandse

Accelerating functional gene discovery in osteoarthritis.

Osteoarthritis causes debilitating pain and disability, resulting in a considerable socioeconomic burden, yet no drugs are available that prevent disease onset or progression. Here, we develop, validate and use rapid-throughput imaging techniques to identify abnormal joint phenotypes in randomly selected mutant mice generated by the International Knockout Mouse Consortium. We identify 14 genes with functional involvement in osteoarthritis pathogenesis, including the homeobox gene Pitx1, and functionally characterize 6 candidate human osteoarthritis genes in mouse models. We demonstrate sensitivity of the methods by identifying age-related degenerative joint damage in wild-type mice. Finally, we phenotype previously generated mutant mice with an osteoarthritis-associated polymorphism in the Dio2 gene by CRISPR/Cas9 genome editing and demonstrate a protective role in disease onset with public health implications. We hope this expanding resource of mutant mice will accelerate functional gene discovery in osteoarthritis and offer drug discovery opportunities for this common, incapacitating chronic disease

Loss of Myotubularin Function Results in T-Tubule Disorganization in Zebrafish and Human Myotubular Myopathy

Myotubularin is a lipid phosphatase implicated in endosomal trafficking in vitro, but with an unknown function in vivo. Mutations in myotubularin cause myotubular myopathy, a devastating congenital myopathy with unclear pathogenesis and no current therapies. Myotubular myopathy was the first described of a growing list of conditions caused by mutations in proteins implicated in membrane trafficking. To advance the understanding of myotubularin function and disease pathogenesis, we have created a zebrafish model of myotubular myopathy using morpholino antisense technology. Zebrafish with reduced levels of myotubularin have significantly impaired motor function and obvious histopathologic changes in their muscle. These changes include abnormally shaped and positioned nuclei and myofiber hypotrophy. These findings are consistent with those observed in the human disease. We demonstrate for the first time that myotubularin functions to regulate PI3P levels in a vertebrate in vivo, and that homologous myotubularin-related proteins can functionally compensate for the loss of myotubularin. Finally, we identify abnormalities in the tubulo-reticular network in muscle from myotubularin zebrafish morphants and correlate these changes with abnormalities in T-tubule organization in biopsies from patients with myotubular myopathy. In all, we have generated a new model of myotubular myopathy and employed this model to uncover a novel function for myotubularin and a new pathomechanism for the human disease that may explain the weakness associated with the condition (defective excitation–contraction coupling). In addition, our findings of tubuloreticular abnormalities and defective excitation-contraction coupling mechanistically link myotubular myopathy with several other inherited muscle diseases, most notably those due to ryanodine receptor mutations. Based on our findings, we speculate that congenital myopathies, usually considered entities with similar clinical features but very disparate pathomechanisms, may at their root be disorders of calcium homeostasis

Molecular Characterization of NRXN1 Deletions from 19,263 Clinical Microarray Cases Identifies Exons Important for Neurodevelopmental Disease Expression

PURPOSE: The purpose of the current study was to assess the penetrance of NRXN1 deletions. METHODS: We compared the prevalence and genomic extent of NRXN1 deletions identified among 19,263 clinically referred cases to that of 15,264 controls. The burden of additional clinically relevant copy-number variations (CNVs) was used as a proxy to estimate the relative penetrance of NRXN1 deletions. RESULTS: We identified 41 (0.21%) previously unreported exonic NRXN1 deletions ascertained for developmental delay/intellectual disability that were significantly greater than in controls (odds ratio (OR) = 8.14; 95% confidence interval (CI): 2.91-22.72; P \u3c 0.0001). Ten (22.7%) of these had a second clinically relevant CNV. Subjects with a deletion near the 3\u27 end of NRXN1 were significantly more likely to have a second rare CNV than subjects with a 5\u27 NRXN1 deletion (OR = 7.47; 95% CI: 2.36-23.61; P = 0.0006). The prevalence of intronic NRXN1 deletions was not statistically different between cases and controls (P = 0.618). The majority (63.2%) of intronic NRXN1 deletion cases had a second rare CNV at a prevalence twice as high as that for exonic NRXN1 deletion cases (P = 0.0035). CONCLUSIONS: The results support the importance of exons near the 5\u27 end of NRXN1 in the expression of neurodevelopmental disorders. Intronic NRXN1 deletions do not appear to substantially increase the risk for clinical phenotypes.Genet Med 19 1, 53-61