cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5120704
title: Supplementary Material for: Interaction Study of the Male Specific Lethal (MSL) Complex and Trans-Acting Dosage Effects in Metafemales of <i>Drosophila melanogaster</i>

description: The effect of ectopic expression of male specific lethal 2 <i>(msl2)</i> on chromatin modification and gene expression was studied in Drosophila diploid females and metafemales (3X;2A). Results show that ectopic expression of MSL2 in transgenic <i>msl2</i> females and metafemales sequesters the MOF histone acetylase to the X, which occurs concordantly with an increase of histone acetylation. Gene expression studies indicate that the X-linked genes are not affected by direct targeting of the MSL complex and the resulting increased H4Lys16 acetylation on the X chromosomes, suggesting one function of the MSL complex is to nullify the effect of a high level of histone acetylation. These results are not consistent with the hypothesis that the presence of the MSL complex conditions a two-fold upregulation. Autosomal gene expression is generally decreased in ectopically expressed MSL2 females, which correlates with the reduced autosomal histone acetylation. Metafemales show dosage compensation of X-linked genes with some autosomal reductions in expression. Interestingly, in metafemales with ectopically expressed MSL2, the autosomal expression is returned to a more normal level. There is a lower autosomal level of histone acetylation compared to the normal metafemales, suggesting a nullifying effect on the negative dosage effect of the X chromosome as previously hypothesized to occur in normal males.
DOI: 10.6084/m9.figshare.5120707.v1
title: Supplementary Material for: Genetic Variants Associated with Complex Human Diseases Show Wide Variation across Multiple Populations

description: <i>Background:</i> The wide use of genome wide association studies (GWAS) has led to the successful identification of multiple genetic susceptibility variants to several complex human diseases. Given the limited amount of data on genetic variation at these loci in populations of non-European origin, we investigated population variation among 11 population groups for loci showing strong and consistent association from GWAS with several complex human diseases. <i>Methods:</i> Data from the International HapMap Project Phase 3, comprising 11 population groups, were used to estimate allele frequencies at loci showing strong and consistent association from GWAS with any of 26 complex human diseases and traits. Allele frequency summary statistics and F<sub>ST</sub> at each locus were used to estimate population differentiation. <i>Results:</i> There is wide variation in allele frequencies and F<sub>ST</sub> across the 11 population groups for susceptibility loci to these complex human diseases and traits. Allele frequencies varied widely across populations, often by as much as 20- to 40-fold. F<sub>ST</sub>, as a measure of population differentiation, also varied widely across the loci studied (for example, 0.019 to 0.201 for type 2 diabetes, 0.022 to 0.520 for prostate cancer loci, and 0.006 to 0.520 for serum lipid levels). <i>Conclusions:</i> The public health risk posed by any of these risk alleles is likely to show wide variation across populations simply as a function of its frequency, and this risk difference may be amplified by gene-gene and gene-environment interactions. These analyses offer compelling reasons for including multiple human populations from different parts of the world in the international effort to use genomic tools to understand disease etiology and differential distribution of diseases across ethnic groups.
DOI: 10.6084/m9.figshare.5120701
title: Supplementary Material for: <i>DTNBP1, NRG1, DAOA</i>, <i>DAO</i> and <i>GRM3</i> Polymorphisms and Schizophrenia: An Association Study

description: <i>Background:</i> Several studies of the dystrobrevin-binding protein 1 gene <i>(DTNBP1)</i>, neuregulin 1 <i>(NRG1)</i>, <i>D</i>-amino-acid oxidase <i>(DAO)</i>, <i>DAO</i> activator <i>(DAOA, G72)</i>, and metabotropic glutamate receptor 3 <i>(GRM3)</i> genes have suggested an association between variants of these genes and schizophrenia. <i>Methods:</i> In a replication attempt, single-nucleotide polymorphisms of the <i>DTNBP1, NRG1, DAO, DAOA, </i>and<i> GRM3 </i>genes were analyzed in three independent Scandinavian schizophrenia case-control samples. <i>Results:</i> One <i>DTNBP1 </i>and three <i>GRM3</i> single-nucleotide polymorphisms showed nominal significant associations to the disease. However, after correction for multiple testing, there were no statistically significant allele, genotype or haplotype case-control differences. <i>Conclusions:</i> The present Scandinavian results do not verify previous associations between the analyzed <i>DTNBP1, NRG1, DAO, DAOA, </i>and<i> GRM3 </i>gene polymorphisms and schizophrenia. Additional studies and meta-analyses are warranted to shed further light on these relationships.
DOI: 10.6084/m9.figshare.5120710.v1
title: Supplementary Material for: Evolution of Brain Size in a Highly Diversifying Lineage of Subterranean Rodent Genus <i>Ctenomys</i> (Caviomorpha: Ctenomyidae)

description: We evaluated brain size evolution in a specialized subterranean mammal, the ctenomyid rodent genus <i>Ctenomys </i>(tuco-tuco) and compared it, within a phylogenetic framework, to other caviomorph rodents differing in body size and modes of life. Although brain size in <i>Ctenomys</i> falls below the regression line obtained for caviomorph rodents, some fossorial species within the sister family Octodontidae, which make use of both above and below ground habitats, have a relatively larger brain size. <i>Ctenomys</i> has experienced a relatively recent and ‘explosive’ cladogenesis which yielded ∼60 living species differing almost one order of magnitude in body size. Based on the evolutionary lag hypothesis between body versus brain size evolution, a negative correlation between encephalization quotient and body size would be expected for a group experiencing such a recent diversification in size. This is because a decrease of body size occurring during the emergence of a new species should produce a correspondingly greater encephalization and vice versa. Despite the fact that the allometric coefficient of brain weight versus body weight for 30 living species of <i>Ctenomys</i> was lower than that obtained for families within Caviomorpha, we failed to find any significant relationship between encephalization and body weight. Finally, the relationship between brain size and metabolism was assessed for those species of <i>Ctenomys</i> in which metabolic data are available. Brain size evolution in <i>Ctenomys</i> is discussed in regards to sensory capabilities and behavioral attributes associated with the occupation of a subterranean ecological niche.
DOI: 10.6084/m9.figshare.5120695
title: Supplementary Material for: Investigating the Molecular Basis for the Virulence of <i>Escherichia coli</i> K5 by Nuclear Magnetic Resonance Analysis of the Capsule Polysaccharide

description: The capsular polysaccharide of <i>Escherichia coli</i> K5 has been hypothesised to promote virulence through its molecular mimicry of host heparan sulphate. To test this hypothesis, we have produced pure oligosaccharides from K5 capsular polysaccharide and investigated their conformational properties with ultra-high-field nuclear magnetic resonance (NMR) (900 MHz). Ultra-high-field affords a significant resolution enhancement over previous studies and allowed a full-atomic assignment of the K5 hexasaccharide for the first time. All carbohydrate rings adopt a <sup>4</sup><i>C</i><sub>1</sub> conformation, the amide sidechains have a <i>trans</i> orientation and the hydroxymethyl group is freely exposed to bulk solvent. Initial models of the glycosidic linkage conformation based upon simple interpretation of NOE cross-peaks suggests that the β1→4 linkage adopts a 3D geometry of φ ≈ 60°, ψ ≈ 0° and the α1→4 linkage prefers φ ≈ –30°, ψ ≈ –30° (φ and ψ being defined by dihedral angles involving linkage protons). In this conformation the overall molecular geometries of K5 polysaccharide, heparan sulphate and even fully-sulphated heparin are remarkably similar. These results substantiate the hypothesis that the K5 capsular polysaccharide confers virulence to <i>E. coli</i> K5 by being a 3D molecular mimetic of host heparan sulphate, helping it to evade detection by the mammalian immune system.
DOI: 10.6084/m9.figshare.5120698
title: Supplementary Material for: Factors Influencing Uptake of Pharmacogenetic Testing in a Diverse Patient Population

description: <i>Background: </i>The successful integration of pharmacogenetic (PGx) testing into clinical care will require attention to patient attitudes. In this study, we aimed to identify the major reasons why patients would or would not consider PGx testing and whether these factors differed by race, socioeconomic and insurance status, and medical history. <i>Methods:</i> We developed and conducted a survey within the adult patient population of the Duke Family Medicine Center. <i>Results:</i> Of 75 completed surveys (65% African-American), 77% indicated they were ‘very likely’ or ‘somewhat likely’ to take a PGx test. Respondents who had experienced a side effect were significantly more likely to indicate they would take a PGx test and expressed greater interest in learning more about testing than those who had not. Drug safety and effectiveness were the major reasons to have PGx testing. Privacy concerns and lack of insurance coverage for testing were the major reasons to decline testing. <i>Conclusions:</i> We found no differences in interest in PGx tests by race or socioeconomic status, but found stronger interest from those with a history of side effects and private insurance. While the overall support of PGx testing is encouraging, greater reassurance of medical privacy and development of educational resources are needed.
DOI: 10.6084/m9.figshare.5120692
title: Supplementary Material for: Increased Expression of Cell–Cell Signaling Genes by Stimulated Mononuclear Leukocytes in Patients with Previous Atherothrombotic Stroke

description: <i>Background/Aims:</i> Inflammation plays an important role in atherosclerosis and stroke. Acute infections are recognized as trigger factors for ischemic stroke. <i>Methods:</i> In this whole genome expression profile study of 15 patients and 15 control subjects, we tested the hypothesis that patients with a history of atherothrombotic stroke show enhanced transcription of inflammatory genes in circulating leukocytes. RNA from unstimulated or lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) was analyzed with Affymetrix U133A GeneChips using a pooling design. Expression of single genes and functional groups of genes was analyzed by global statistical tests. <i>Results:</i> A total of 10,197 probe sets showed positive calls. After correction for multiple testing no single probe set revealed significant differences either without or with LPS stimulation. However, significant global expression differences were found upon LPS stimulation for the group of genes that are involved in cell–cell signaling. <i>Conclusion:</i> LPS stimulation of PBMCs, a condition mimicking bacterial infection, induces differential expression of a group of cell–cell signaling genes in patients with previous atherothrombotic stroke. This finding can be caused by genetic differences between both groups, but acquired risk factors, medication and technical factors may also have contributed to the result.
DOI: 10.6084/m9.figshare.5120686
title: Supplementary Material for: Host Genetics, Steatosis and Insulin Resistance among African Americans and Caucasian Americans with Hepatitis C Virus Genotype-1 Infection

description: Hepatic steatosis is the accumulation of fat in liver cells. Insulin resistance (IR) occurs when normal amounts of insulin do not stimulate insulin activity in cells. Both conditions have been described in hepatitis C virus (HCV) infection and are thought to be biologically related. This study examined the association of genetic variants with steatosis and IR among 167 African Americans and 184 Caucasian Americans with HCV genotype-1. Steatosis was defined as at least 5% of fat in cells on liver biopsy. IR was quantified as a score greater than 2 from the Homeostasis Model Assessment, version 2.2 (HOMA2-IR). Associations were investigated by estimating odds ratios separately by race. Statistically significant associations (p &lt; 0.05) were observed for variants in <i>interleukin-10 (IL10)</i>, <i>leptin receptor (LEPR)</i>, <i>interleukin-6 (IL6)</i> and <i>transforming growth factor beta-1 (TGF-</i>β<i>1)</i> for both outcomes. Some significant interactions were observed between <i>IL10,</i><i>LEPR </i>and <i>TGF-</i>β<i>1 </i>polymorphisms and HOMA2-IR scores when examining steatosis. The interaction of HOMA2-IR and <i>IL10</i> was consistent in both races whereas for <i>LEPR</i> and <i>TGF-</i>β<i>1</i> the interactions were statistically significant in only one of the racial groups.These results could imply that some <i>IL10,</i><i>LEPR </i>and <i>TGF-</i>β<i>1 </i>polymorphisms may modify an association between steatosis and IR.
DOI: 10.6084/m9.figshare.5120689
title: Supplementary Material for: Secretion of Fibrinolytic Enzymes Facilitates Human Mesenchymal Stem Cell Invasion into Fibrin Clots

description: Adult human mesenchymal stem cells (hMSC) are involved in wound healing and regeneration of mesodermal tissue, but the underlying homing mechanisms are not well understood. Fibrin clot formation is associated with most wound healing processes and potentially guides the recruitment of hMSC. The objective of this study is the investigation of a fibrinolytic capacity, which is required for hMSC to migrate into a wounded tissue and thus to contribute to tissue regeneration. Using RT-PCR, semiquantitative real-time PCR and ELISA, we detected key components of the fibrinolytic cascade, including the urokinase plasminogen activator (uPA) and its receptor (uPAR), the tissue plasminogen activator (tPA) and the plasminogen activator inhibitor (PAI), suggesting a strong fibrinolytic activity of hMSC. To test this activity in a functional assay, we cultured fibrin-embedded hMSC in vitro for 7 days. The cells efficiently dissolved the surrounding fibrin mesh into the fibrin degradation products, the fibrinopeptides. The fibrinolytic activity of hMSC and human dermal fibroblasts, known to be critically involved in skin wound extracellular matrix remodeling, was similar. Our results suggest that a high intrinsic fibrinolytic capacity of hMSC mediates the invasion into a fibrin clot of a wounded tissue.
DOI: 10.6084/m9.figshare.5120695.v1
title: Supplementary Material for: Investigating the Molecular Basis for the Virulence of <i>Escherichia coli</i> K5 by Nuclear Magnetic Resonance Analysis of the Capsule Polysaccharide

description: The capsular polysaccharide of <i>Escherichia coli</i> K5 has been hypothesised to promote virulence through its molecular mimicry of host heparan sulphate. To test this hypothesis, we have produced pure oligosaccharides from K5 capsular polysaccharide and investigated their conformational properties with ultra-high-field nuclear magnetic resonance (NMR) (900 MHz). Ultra-high-field affords a significant resolution enhancement over previous studies and allowed a full-atomic assignment of the K5 hexasaccharide for the first time. All carbohydrate rings adopt a <sup>4</sup><i>C</i><sub>1</sub> conformation, the amide sidechains have a <i>trans</i> orientation and the hydroxymethyl group is freely exposed to bulk solvent. Initial models of the glycosidic linkage conformation based upon simple interpretation of NOE cross-peaks suggests that the β1→4 linkage adopts a 3D geometry of φ ≈ 60°, ψ ≈ 0° and the α1→4 linkage prefers φ ≈ –30°, ψ ≈ –30° (φ and ψ being defined by dihedral angles involving linkage protons). In this conformation the overall molecular geometries of K5 polysaccharide, heparan sulphate and even fully-sulphated heparin are remarkably similar. These results substantiate the hypothesis that the K5 capsular polysaccharide confers virulence to <i>E. coli</i> K5 by being a 3D molecular mimetic of host heparan sulphate, helping it to evade detection by the mammalian immune system.
DOI: 10.6084/m9.figshare.5120683
title: Supplementary Material for: Influence of Cyclooxygenase-1 Genotype on ex vivo Aspirin Response in Patients at Risk for Stroke

description: <i>Background:</i> We sought to determine whether cyclooxygenase-1 <i>(PTGS1)</i> genotype is associated with the ability of aspirin to inhibit platelet aggregation in patients at risk for stroke. <i>Methods:</i> Blood and urine samples were collected from 60 subjects, including 28 African Americans, who were taking aspirin for primary or secondary stroke prevention. Samples were analyzed for the <i>PTGS1 </i>A–707G, <i>PTGS1</i> P17L, and glycoprotein IIIa (<i>ITGB3</i>)P1<sup>A1/A2</sup> genotypes, ex-vivo platelet aggregation, serum cholesterol, plasma salicylate levels, and urinary 11-dehydrothromboxane B<sub>2</sub> (11-dhTxB<sub>2</sub>) concentrations. The association between <i>PTGS1 </i>A–707G and P17L genotypes and aspirin response, as assessed by ex vivo studies and 11-dhTxB<sub>2</sub> concentrations, was evaluated by statistical testing and nonlinear mapping. <i>Results:</i> Salicylate concentrations, <i>ITGB3</i> genotype distribution and 11-dhTxB<sub>2</sub> concentrations were similar among <i>PTGS1</i> genotype groups. More subjects with the <i>PTGS1 </i>17PP versus PL genotype had incomplete ex-vivo inhibition of platelet aggregation by aspirin (57 vs. 20%; p = 0.04). Fifty-nine percent of subjects homozygous for both the <i>PTGS</i> –707A and 17P alleles, but none with both the <i>PTGS1</i> –707G and 17L alleles had incomplete inhibition with aspirin; p = 0.04. Similarly, nonlinear mapping showed a direct relationship between the <i>PTGS1</i> 17P allele and decreased aspirin response. When analyzed separately by ethnicity, the association with the P17L genotype and aspirin response persisted in African Americans, but not Caucasians. <i>Conclusions:</i> Our data suggest that the <i>PTGS1</i> P17L genotype contributes to response to aspirin as assessed by ex-vivo platelet aggregation. Our data further suggest that the association between <i>PTGS1</i> genotype and aspirin response might vary by ethnicity.
DOI: 10.6084/m9.figshare.5120677
title: Supplementary Material for: Infections Related to Airway Stenting: A Systematic Review

description: <i>Background:</i> Airway stenting is nowadays an established method for the palliative and/or curative treatment of central airways obstruction. However, complications related to the use of airway stents have been reported. <i>Objective:</i> We endeavored to systematically evaluate the currently available evidence regarding the infections associated with airway stenting. <i>Methods:</i> We independently searched in PubMed for relevant reports. We considered articles which reported on clinical infections related to airway stenting. A case was identified as stent-associated respiratory tract infection (SARTI) according to the authors of the individual papers, based on clinical findings with or without radiological or microbiological confirmation. <i>Results:</i> Twenty-three articles (19 cohorts/case series and 4 case reports), involving 501 patients with airway stents, were included. The indication for airway stenting was malignancy and benign disease in 45 and 55% of the included patients, respectively. Ninety-three (19%) out of the 501 stented patients experienced SARTI. Pneumonia was the most common type of SARTI (47%), followed by bronchial infection (24%), cavitary pneumonia/lung abscess and intraluminal fungus ball. <i>Staphylococcus aureus</i> (39%) and <i>Pseudomonas aeruginosa</i> (28%) were the most commonly identified pathogens. Twenty-six (68%) out of the 38 patients with SARTI, for whom outcome data were available, died. <i>Conclusion:</i> The accumulated and evaluated evidence suggests that SARTI probably involves 1 in 5 patients with airway stent. Although the possibility of SARTI should not discourage the interventional pneumologists from inserting airway stents, the data seem to underline the urgent need for establishing a consensus definition and diagnostic criteria for SARTI.
DOI: 10.6084/m9.figshare.5120686.v1
title: Supplementary Material for: Host Genetics, Steatosis and Insulin Resistance among African Americans and Caucasian Americans with Hepatitis C Virus Genotype-1 Infection

description: Hepatic steatosis is the accumulation of fat in liver cells. Insulin resistance (IR) occurs when normal amounts of insulin do not stimulate insulin activity in cells. Both conditions have been described in hepatitis C virus (HCV) infection and are thought to be biologically related. This study examined the association of genetic variants with steatosis and IR among 167 African Americans and 184 Caucasian Americans with HCV genotype-1. Steatosis was defined as at least 5% of fat in cells on liver biopsy. IR was quantified as a score greater than 2 from the Homeostasis Model Assessment, version 2.2 (HOMA2-IR). Associations were investigated by estimating odds ratios separately by race. Statistically significant associations (p &lt; 0.05) were observed for variants in <i>interleukin-10 (IL10)</i>, <i>leptin receptor (LEPR)</i>, <i>interleukin-6 (IL6)</i> and <i>transforming growth factor beta-1 (TGF-</i>β<i>1)</i> for both outcomes. Some significant interactions were observed between <i>IL10,</i><i>LEPR </i>and <i>TGF-</i>β<i>1 </i>polymorphisms and HOMA2-IR scores when examining steatosis. The interaction of HOMA2-IR and <i>IL10</i> was consistent in both races whereas for <i>LEPR</i> and <i>TGF-</i>β<i>1</i> the interactions were statistically significant in only one of the racial groups.These results could imply that some <i>IL10,</i><i>LEPR </i>and <i>TGF-</i>β<i>1 </i>polymorphisms may modify an association between steatosis and IR.
DOI: 10.6084/m9.figshare.5120692.v1
title: Supplementary Material for: Increased Expression of Cell–Cell Signaling Genes by Stimulated Mononuclear Leukocytes in Patients with Previous Atherothrombotic Stroke

description: <i>Background/Aims:</i> Inflammation plays an important role in atherosclerosis and stroke. Acute infections are recognized as trigger factors for ischemic stroke. <i>Methods:</i> In this whole genome expression profile study of 15 patients and 15 control subjects, we tested the hypothesis that patients with a history of atherothrombotic stroke show enhanced transcription of inflammatory genes in circulating leukocytes. RNA from unstimulated or lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) was analyzed with Affymetrix U133A GeneChips using a pooling design. Expression of single genes and functional groups of genes was analyzed by global statistical tests. <i>Results:</i> A total of 10,197 probe sets showed positive calls. After correction for multiple testing no single probe set revealed significant differences either without or with LPS stimulation. However, significant global expression differences were found upon LPS stimulation for the group of genes that are involved in cell–cell signaling. <i>Conclusion:</i> LPS stimulation of PBMCs, a condition mimicking bacterial infection, induces differential expression of a group of cell–cell signaling genes in patients with previous atherothrombotic stroke. This finding can be caused by genetic differences between both groups, but acquired risk factors, medication and technical factors may also have contributed to the result.