cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.12905819
title: Supplementary Material for: <b><i>JAK1</i></b> rs310241 and <b><i>JAK3</i></b> rs3008 Genotypes May Increase Susceptibility to Psoriasis: A Case Control Study

description: <b><i>Background:</i></b> Janus kinases (JAKs) are a family of non-receptor protein tyrosine kinases that are expressed in a variety of tissues. Several JAK-controlled cytokine receptor pathways are incriminated in the initiation and progression of psoriasis. Genetic polymorphisms influencing JAK expression would be anticipated to have a great impact on disease activity. <b><i>Objective:</i></b> The aim of the study was to evaluate the association between <i>JAK1</i> rs310241 and <i>JAK3</i> rs3008 polymorphisms and the risk of developing psoriasis. <b><i>Methods:</i></b> Blood samples of 150 patients and 120 controls were screened for nucleotide polymorphisms in <i>JAK1</i> rs310241 and <i>JAK3</i> rs3008 genes by using polymerase chain reaction<b> (</b>PCR)-restriction fragment length polymorphism technique. <b><i>Results:</i></b> The GG genotype of the <i>JAK1</i> rs310241 and <i>JAK3 rs3008</i> genes was significantly associated with an increase in psoriasis risk (<i>p</i> = 0.000, OR = 7.7, 95% CI = 2.8–21.5; <i>p</i> = 0.003, OR = 3.3, 95% CI = 1.5–6.9, respectively). The G allele of both genes was also associated with psoriasis susceptibility (<i>p</i> = 0.000, OR = 2.0, 95% CI = 1.4–2.8; <i>p</i> = 0.002, OR = 1.7, 95% CI = 1.2–2.4, respectively). <b><i>Conclusion:</i></b> The results indicate a possible association between <i>JAK1</i> rs310241 and <i>JAK3</i> rs3008 gene polymorphisms and susceptibility to psoriasis. These findings validate the importance of these molecules in psoriasis and may enable the identification of the individuals most susceptible to the disease.
DOI: 10.6084/m9.figshare.5121649
title: Supplementary Material for: A Principal Components-Based Clustering Method to Identify Variants Associated with Complex Traits

description: <i>Background:</i> Multivariate methods ranging from joint SNP to principal components analysis (PCA) have been developed for testing multiple markers in a region for association with disease and disease-related traits. However, these methods suffer from low power and/or the inability to identify the subset of markers contributing to evidence for association under various scenarios. <i>Methods:</i> We introduce orthoblique principal components-based clustering (OPCC) as an alternative approach to identify specific subsets of markers showing association with a quantitative outcome of interest. We demonstrate the utility of OPCC using simulation studies and an example from the literature on type 2 diabetes. <i>Results:</i> Compared to traditional methods, OPCC has similar or improved power under various scenarios of linkage disequilibrium structure and genotype availability. Most importantly, our simulations show how OPCC accurately parses large numbers of markers to a subset containing the causal variant or its proxy. <i>Conclusion:</i> OPCC is a powerful and efficient data reduction method for detecting associations between gene variants and disease-related traits. Unlike alternative methodologies, OPCC has the ability to isolate the effect of causal SNP(s) from among large sets of markers in a candidate region. Therefore, OPCC is an improvement over PCA for testing multiple SNP associations with phenotypes of interest.
DOI: 10.6084/m9.figshare.5121652.v1
title: Supplementary Material for: Regulation of Gap Junctional Communication by Astrocytic Mitochondrial K<sub>ATP</sub> Channels following Neurotoxin Administration in in vitro and in vivo Models

description: It is known that neuronal ATP-sensitive potassium (K<sub>ATP</sub>) channels and astrocytic gap junctions (GJs) are involved in the mechanism underlying neurodisorders. The K<sub>ATP</sub> channels exist also in glial cells, and the objective of this study was to determine whether the astrocytic K<sub>ATP</sub> channels exert their effect on neurotoxin-induced neurodysfunction through regulating the astrocytic GJ function. The results showed that diazoxide, a selective mitochondrial K<sub>ATP</sub> (mitoK<sub>ATP</sub>) channel opener, enhanced the GJ coupling, but 5-hydroxydecanoate, a selective mitoK<sub>ATP</sub> channel blocker that significantly inhibits GJ coupling in vitro did not. Activation of astrocytic mitoK<sub>ATP</sub> channels alleviated kainic acid-induced dysfunction of GJ intercellular communication. Finally, activation of mitoK<sub>ATP</sub> channels improved the astrocytic GJ coupling in the hippocampus after seizures due to the colabeling of GJ subunit connexin 43 and connexin 45 with glial marker and was increased substantially by the administration of diazoxide. Western blot demonstrated that the mitoK<sub>ATP</sub> channels regulated the expression of connexin 43 (P2; active form) and connexin 45 in the epileptic hippocampus. These findings demonstrate that activation of astrocytic mitoK<sub>ATP</sub> channels improves the GJ function in astrocytes, indicating that the effect of the astrocytic mitoK<sub>ATP</sub> channels on neurotoxin-induced neurodysfunction might be, in part, through the regulation of the GJ-coupled spatial buffering in the hippocampus.
DOI: 10.6084/m9.figshare.5121637
title: Supplementary Material for: Application of the Optimal Discovery Procedure to Genetic Case-Control Studies: Comparison with p Values and Asymptotic Bayes Factors

description: <i>Objectives:</i> The power of genetic association studies is limited by stringent levels of statistical significance. To improve power, Bayes factors (BFs) have been suggested as an alternative measure to the p value, and Storey recently introduced an optimal discovery procedure (ODP) for multiple testing. We aimed to adapt the ODP to genetic case-control studies and to compare its power to p values and asymptotic BFs (ABFs). <i>Methods:</i> We propose estimators of the ODP based on prospective and retrospective likelihoods. We performed simulations based on independent common SNPs and on sequence data including rare variants. Effects of causal SNPs were simulated under various distributions of effect size. <i>Results:</i> The true ODP is never outperformed, but the estimated ODP has similar power to p values and ABFs. For common SNPs the ODP offers power advantages only in extreme scenarios. However, for rare variants the ODP and ABF detect more associations at low false-positive rates than do p values. <i>Conclusions:</i> The ODP can provide higher power than p values for genetic case-control studies of common variants. However, as the ABF has similar power to the ODP and is computed more rapidly, it is our currently preferred method.
DOI: 10.6084/m9.figshare.5121640
title: Supplementary Material for: Antiviral Resistance Mutations and Genotype-Associated Amino Acid Substitutions in Treatment-Naïve Hepatitis B Virus-Infected Individuals from the Indian Subcontinent

description: <i>Background/Aims:</i> Antiviral resistance is a major challenge to the treatment currently available for hepatitis B virus (HBV). In this study, mutations that may affect the antiviral efficacy in treatment-naïve HBV-infected individuals were analyzed. <i>Methods:</i> Ninety-seven treatment-naïve HBV-infected individuals were included in this study. HBV reverse transcriptase (rt) domains were sequenced and nucleotide differences were compared to GenBank wild-type sequences. Furthermore, HBV genotypes, subgenotypes and subtypes were determined by analyzing surface gene sequences. <i>Results:</i> An adefovir-related rtI233V mutation was identified in 4 subjects. The rtS213T lamivudine and entecavir refractory mutant was presented in 3 individuals. Altogether, drug-related, atypical and novel HBVrt amino acid substitutions were seen in 73 positions. The HBV genotypes A, C, D and G were depicted in 15, 21, 60 and 1 individuals, respectively. There were 17 HBVrt amino acid substitutions that are associated with certain genotypes of HBV. Mutations in HBVrt corresponded to established surface gene mutations in 9 patients. <i>Conclusion:</i> This data shows that antiviral-resistant HBV strains do exist in treatment-naïve individuals in this region. Further studies are essential to characterize the role of HBVrt amino acid substitutions in response to anti-HBV therapy.
DOI: 10.6084/m9.figshare.5121643
title: Supplementary Material for: A Single D<sub>H</sub> Gene Segment Is Sufficient for the Establishment of an Asthma Phenotype in a Murine Model of Allergic Airway Inflammation

description: <i>Background:</i> We have previously shown that the allergic sensitization to ovalbumin does not represent a superantigen-like immune response. In gene-targeted mice (ΔD-iD) with a single modified <i>Diversity</i> gene segment (D<sub>H</sub>) of the immunoglobulin heavy chain, enriched for charged amino acids, the asthma phenotype in a murine model was markedly alleviated compared to wild-type animals. <i>Objective:</i> We now sought to determine whether the confinement to a single D<sub>H</sub> gene segment alone leads to a reduced allergic phenotype. <i>Methods:</i> We examined another gene-targeted mouse strain (ΔD-DFL) with a single D<sub>H</sub> gene segment which encodes for neutral amino acids, thus reflecting the preferential repertoire in wild-type mice. Mice were sensitized intraperitoneally to ovalbumin. <i>Results:</i> Despite the constraint to a single D<sub>H</sub> gene segment, ΔD-DFL mice mounted high total and allergen-specific IgG<sub>1</sub> and IgE serum levels after sensitization to ovalbumin. The affinity constants of allergen-specific IgG<sub>1</sub> antibodies did not differ between ΔD-DFL and wild type. Following challenge with aerosolized allergen, a marked local T<sub>H</sub>2 cytokine response and an eosinophilic airway inflammation developed. Quantitative histology revealed increased mucus production and intense goblet cell metaplasia which were identical to those in wild type. Moreover, ΔD-DFL mice developed an airway hyperreactivity to methacholine and to the specific allergen, which both did not differ from those in wild-type animals. <i>Conclusion:</i> A single D<sub>H</sub> gene segment is sufficient for the establishment of the asthma phenotype in a murine model of allergic airway inflammation. Thus, the allergic phenotype depends on the amino acid composition and not on the diversity of the classical antigen-binding site.
DOI: 10.6084/m9.figshare.5121646
title: Supplementary Material for: Pitx2c Modulates Cardiac-Specific Transcription Factors Networks in Differentiating Cardiomyocytes from Murine Embryonic Stem Cells

description: <i>Aim:</i> The knowledge of the molecular signals that control cell differentiation into cardiomyocytes is critical to apply cell-based therapies and repair an injured heart. The transcription factor Pitx2 has essential roles in the development of different organs including the heart. Although a direct role of Pitx2 in the developing myocardium has recently been reported, the molecular pathways driven by Pitx2 as well as its cardiac target genes remain largely unexplored. The aim of this study was to unravel the molecular mechanisms driven by Pitx2 during the process of cardiomyocyte differentiation in vitro in mouse embryonic stem cell-derived cardiomyocytes. <i>Methods and Results:</i> Pitx2c was overexpressed in the R1-embryonic stem cell line. mRNA levels and protein distribution of several specific cardiac genes were analyzed by real-time PCR and immunohistochemistry experiments in R1-embryonic stem cell-derived beating areas at different stages of in vitro differentiation. Our results show that overexpression of Pitx2c in embryonic stem cell-derived cardiomyocytes is able to dynamically upregulate several cardiac-enriched transcription factors such as Isl1, Mef2c and Gata4. Additionally, Pitx2c induces the expression of chamber-specific cardiac genes such as Tbx5, Nppa and Cx40. These data were validated in an in vivo model of Pitx2 loss of function. <i>Conclusion:</i> Taken together, these results demonstrate that Pitx2 plays a major role reinforcing the transcriptional program of cardiac differentiation.
DOI: 10.6084/m9.figshare.5121646.v1
title: Supplementary Material for: Pitx2c Modulates Cardiac-Specific Transcription Factors Networks in Differentiating Cardiomyocytes from Murine Embryonic Stem Cells

description: <i>Aim:</i> The knowledge of the molecular signals that control cell differentiation into cardiomyocytes is critical to apply cell-based therapies and repair an injured heart. The transcription factor Pitx2 has essential roles in the development of different organs including the heart. Although a direct role of Pitx2 in the developing myocardium has recently been reported, the molecular pathways driven by Pitx2 as well as its cardiac target genes remain largely unexplored. The aim of this study was to unravel the molecular mechanisms driven by Pitx2 during the process of cardiomyocyte differentiation in vitro in mouse embryonic stem cell-derived cardiomyocytes. <i>Methods and Results:</i> Pitx2c was overexpressed in the R1-embryonic stem cell line. mRNA levels and protein distribution of several specific cardiac genes were analyzed by real-time PCR and immunohistochemistry experiments in R1-embryonic stem cell-derived beating areas at different stages of in vitro differentiation. Our results show that overexpression of Pitx2c in embryonic stem cell-derived cardiomyocytes is able to dynamically upregulate several cardiac-enriched transcription factors such as Isl1, Mef2c and Gata4. Additionally, Pitx2c induces the expression of chamber-specific cardiac genes such as Tbx5, Nppa and Cx40. These data were validated in an in vivo model of Pitx2 loss of function. <i>Conclusion:</i> Taken together, these results demonstrate that Pitx2 plays a major role reinforcing the transcriptional program of cardiac differentiation.
DOI: 10.6084/m9.figshare.5121634
title: Supplementary Material for: Functions of Lipopeptides Bacillomycin D and Fengycin in Antagonism of <i>Bacillus amyloliquefaciens</i> C06 towards <i>Monilinia fructicola</i>

description: In previous studies, <i>Bacillus amyloliquefaciens</i> C06 has been proven to be effective in controlling brown rot of stone fruit caused by <i>Monilinia fructicola.</i> When tested in vitro, cell-free filtrate of <i>B. amyloliquefaciens</i> C06 significantly inhibited mycelial growth and conidial germination of the fungal pathogen. This study aimed to determine the role of the antifungal compound(s) in the cell-free filtrate of <i>B. amyloliquefaciens</i> C06 by an approach combining a DNA-based suppression subtractive hybridization (SSH) method with MALDI-TOF-MS analysis. It was demonstrated that <i>B. amyloliquefaciens</i> C06 harbored two genes, <i>bmyC</i> and <i>fenD</i>, involved in biosynthesis of bacillomycin D and fengycin, two lipopeptides belonging to the iturin and fengycin family, respectively. To determine the roles of bacillomycin D and fengycin of <i>B. amyloliquefaciens</i> C06 in suppressing <i>M. fructicola</i>, the mutants of <i>B. amyloliquefaciens</i> C06 deficient in producing bacillomy- cin D, fengycin or both were constructed, and evaluated in vitro together with the wild-type <i>B. amyloliquefaciens</i> C06. The results indicated that bacillomycin D and fengycin jointly contributed to the inhibition of conidial germination of <i>M. fructicola, </i>and fengycin played a major role in suppressing mycelial growth of the fungal pathogen.
DOI: 10.6084/m9.figshare.5121649.v1
title: Supplementary Material for: A Principal Components-Based Clustering Method to Identify Variants Associated with Complex Traits

description: <i>Background:</i> Multivariate methods ranging from joint SNP to principal components analysis (PCA) have been developed for testing multiple markers in a region for association with disease and disease-related traits. However, these methods suffer from low power and/or the inability to identify the subset of markers contributing to evidence for association under various scenarios. <i>Methods:</i> We introduce orthoblique principal components-based clustering (OPCC) as an alternative approach to identify specific subsets of markers showing association with a quantitative outcome of interest. We demonstrate the utility of OPCC using simulation studies and an example from the literature on type 2 diabetes. <i>Results:</i> Compared to traditional methods, OPCC has similar or improved power under various scenarios of linkage disequilibrium structure and genotype availability. Most importantly, our simulations show how OPCC accurately parses large numbers of markers to a subset containing the causal variant or its proxy. <i>Conclusion:</i> OPCC is a powerful and efficient data reduction method for detecting associations between gene variants and disease-related traits. Unlike alternative methodologies, OPCC has the ability to isolate the effect of causal SNP(s) from among large sets of markers in a candidate region. Therefore, OPCC is an improvement over PCA for testing multiple SNP associations with phenotypes of interest.
DOI: 10.6084/m9.figshare.5121631
title: Supplementary Material for: The Progressive Ankylosis Protein Regulates Cementum Apposition and Extracellular Matrix Composition

description: <i>Background/Aims:</i> Tooth root cementum is sensitive to modulation of inorganic pyrophosphate (PP<sub>i</sub>), an inhibitor of hydroxyapatite precipitation. Factors increasing PP<sub>i</sub> include progressive ankylosis protein (ANK) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) while tissue nonspecific alkaline phosphatase hydrolyzes PP<sub>i</sub>. Studies here aimed to define the role of ANK in root and cementum by analyzing tooth development in <i>Ank</i> knock-out (KO) mice versus wild type. <i>Materials and Methods:</i> Periodontal development in KO versus control mice was analyzed by histology, histomorphometry, immunohistochemistry, in situ hybridization, electron microscopy, and nanoindentation. Cementoblast cultures were used in vitro to provide mechanistic underpinnings for PP<sub>i</sub> modulation of cell function. <i>Results:</i> Over the course of root development, <i>Ank</i> KO cervical cementum became 8- to 12-fold thicker than control cervical cementum. Periodontal ligament width was maintained and other dentoalveolar tissues, including apical cementum, were unaltered. Cervical cementum uncharacteristically included numerous cells, from rapid cementogenesis. <i>Ank </i>KO increased osteopontin and dentin matrix protein 1 gene and protein expression, and markedly increased NPP1 protein expression in cementoblasts but not in other cell types. Conditional ablation of <i>Ank</i> in joints and periodontia confirmed a local role for ANK in cementogenesis. In vitro studies employing cementoblasts indicated that <i>Ank</i> and <i>Enpp1</i> mRNA levels increased in step with mineral nodule formation, supporting a role for these factors in regulation of cementum matrix mineralization. <i>Conclusion: </i>ANK, by modulating local PP<sub>i</sub>, controls cervical cementum apposition and extracellular matrix. Loss of ANK created a local environment conducive to rapid cementogenesis; therefore, approaches modulating PP<sub>i</sub> in periodontal tissues have potential to promote cementum regeneration.
DOI: 10.6084/m9.figshare.5121634.v1
title: Supplementary Material for: Functions of Lipopeptides Bacillomycin D and Fengycin in Antagonism of <i>Bacillus amyloliquefaciens</i> C06 towards <i>Monilinia fructicola</i>

description: In previous studies, <i>Bacillus amyloliquefaciens</i> C06 has been proven to be effective in controlling brown rot of stone fruit caused by <i>Monilinia fructicola.</i> When tested in vitro, cell-free filtrate of <i>B. amyloliquefaciens</i> C06 significantly inhibited mycelial growth and conidial germination of the fungal pathogen. This study aimed to determine the role of the antifungal compound(s) in the cell-free filtrate of <i>B. amyloliquefaciens</i> C06 by an approach combining a DNA-based suppression subtractive hybridization (SSH) method with MALDI-TOF-MS analysis. It was demonstrated that <i>B. amyloliquefaciens</i> C06 harbored two genes, <i>bmyC</i> and <i>fenD</i>, involved in biosynthesis of bacillomycin D and fengycin, two lipopeptides belonging to the iturin and fengycin family, respectively. To determine the roles of bacillomycin D and fengycin of <i>B. amyloliquefaciens</i> C06 in suppressing <i>M. fructicola</i>, the mutants of <i>B. amyloliquefaciens</i> C06 deficient in producing bacillomy- cin D, fengycin or both were constructed, and evaluated in vitro together with the wild-type <i>B. amyloliquefaciens</i> C06. The results indicated that bacillomycin D and fengycin jointly contributed to the inhibition of conidial germination of <i>M. fructicola, </i>and fengycin played a major role in suppressing mycelial growth of the fungal pathogen.
DOI: 10.6084/m9.figshare.5121637.v1
title: Supplementary Material for: Application of the Optimal Discovery Procedure to Genetic Case-Control Studies: Comparison with p Values and Asymptotic Bayes Factors

description: <i>Objectives:</i> The power of genetic association studies is limited by stringent levels of statistical significance. To improve power, Bayes factors (BFs) have been suggested as an alternative measure to the p value, and Storey recently introduced an optimal discovery procedure (ODP) for multiple testing. We aimed to adapt the ODP to genetic case-control studies and to compare its power to p values and asymptotic BFs (ABFs). <i>Methods:</i> We propose estimators of the ODP based on prospective and retrospective likelihoods. We performed simulations based on independent common SNPs and on sequence data including rare variants. Effects of causal SNPs were simulated under various distributions of effect size. <i>Results:</i> The true ODP is never outperformed, but the estimated ODP has similar power to p values and ABFs. For common SNPs the ODP offers power advantages only in extreme scenarios. However, for rare variants the ODP and ABF detect more associations at low false-positive rates than do p values. <i>Conclusions:</i> The ODP can provide higher power than p values for genetic case-control studies of common variants. However, as the ABF has similar power to the ODP and is computed more rapidly, it is our currently preferred method.