cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5120398
title: Supplementary Material for: Prediction and Experimental Testing of Ferric Uptake Regulator Regulons in Vibrios

description: Iron homeostasis is in many bacteria regulated by the ferric uptake regulator (Fur). Despite the available information on Fur regulons, it is likely that there are Fur-regulated genes and operons that are unique to vibrios, and knowledge into these can potentially provide new insights into vibrio virulence and pathogenesis. We constructed a vibrio-specific alignment matrix based on Fur-binding sites from the literature and used existing software (Patser) to search five published vibrio genomes and the <i>Vibrio salmonicida</i> draft genome for Fur-regulated genes. The consensus Fur-binding site from our matrix is 5′-AATGANAATNATTNTCATT-3′. Fur-binding motifs were found associated with 50–61 single genes and 16–20 operons in each genome. Predictions were tested by monitoring the expression of a subset of genes and operons in <i>V. salmonicida</i>. Six previously undescribed Fur-regulated genes showed increased expression under iron-restrictive conditions. Our work provides a comprehensive list of predicted Fur regulons in six vibrio genomes, which may be used to generate new hypotheses for future experiments.
DOI: 10.6084/m9.figshare.5120392.v1
title: Supplementary Material for: Granule Formation in NGF-Cultured Mast Cells Is Associated with Expressions of Pyruvate Kinase Type M2 and Annexin I Proteins

description: <i>Background:</i> Nerve growth factor (NGF) is a potent mediator, which regulates characteristics of mast cells, but its biological function is not well characterized. This study aimed to screen proteins associated with the maturation of human mast cells-1 (HMC-1) or mouse bone marrow-derived mast cells (BMMCs) cultured with NGF, and to examine the functions of proteins involved. <i>Methods:</i> NGF (10 ng/ml) was added to cell culture medium every other day for 10 days for HMC-1 or twice a week for 5 weeks for BMMCs. Granule formation was determined by electron microscopy or May-Grünwald-Giemsa staining, TNF-α by ELISA, expressions of various proteins by two-dimensional gel electrophoresis (2-DE), siRNA transfection by Lipofectamine 2000, and the expressions of pyruvate kinase and annexin I by immunoblotting. <i>Results:</i> After NGF treatment, granule formation and total amounts of granular mediator, TNF-α increased in both mast cells. This TNF-α was released by calcium ionophore or by antigen/antibody reaction. Expressions of pyruvate kinase and annexin I obtained by 2-DE were confirmed by immunoblotting and siRNA-transfected HMC-1 cells. Expressions of proteins, granule formation and TNF-α content were blocked by both the TrkA inhibitor, K252a, and the ERK inhibitor, PD98059, but not by the PI3 kinase inhibitors, LY294002 and wortmannin. <i>Conclusion:</i> These data suggest that pyruvate kinase and annexin I expressed by NGF contribute to granule formation containing TNF-α as well as other mediators in mast cells, which play a major role in allergic diseases via a TrkA/ERK pathway.
DOI: 10.6084/m9.figshare.5120398.v1
title: Supplementary Material for: Prediction and Experimental Testing of Ferric Uptake Regulator Regulons in Vibrios

description: Iron homeostasis is in many bacteria regulated by the ferric uptake regulator (Fur). Despite the available information on Fur regulons, it is likely that there are Fur-regulated genes and operons that are unique to vibrios, and knowledge into these can potentially provide new insights into vibrio virulence and pathogenesis. We constructed a vibrio-specific alignment matrix based on Fur-binding sites from the literature and used existing software (Patser) to search five published vibrio genomes and the <i>Vibrio salmonicida</i> draft genome for Fur-regulated genes. The consensus Fur-binding site from our matrix is 5′-AATGANAATNATTNTCATT-3′. Fur-binding motifs were found associated with 50–61 single genes and 16–20 operons in each genome. Predictions were tested by monitoring the expression of a subset of genes and operons in <i>V. salmonicida</i>. Six previously undescribed Fur-regulated genes showed increased expression under iron-restrictive conditions. Our work provides a comprehensive list of predicted Fur regulons in six vibrio genomes, which may be used to generate new hypotheses for future experiments.
DOI: 10.6084/m9.figshare.5120401.v1
title: Supplementary Material for: <i>DNAI1</i> Mutations Explain Only 2% of Primary Ciliary Dykinesia

description: <i>Background:</i> Primary ciliary dyskinesia (PCD) is a rare recessive hereditary disorder characterized by dysmotility to immotility of ciliated and flagellated structures. Its main symptoms are respiratory, caused by defective ciliary beating in the epithelium of the upper airways (nose, bronchi and paranasal sinuses). Impairing the drainage of inhaled microorganisms and particles leads to recurrent infections and pulmonary complications. To date, 5 genes encoding 3 dynein protein arm subunits <i>(DNAI1</i>, <i>DNAH5</i> and <i>DNAH11)</i>, the kinase <i>TXNDC3</i> and the X-linked <i>RPGR</i> have been found to be mutated in PCD. <i>Objectives:</i> We proposed to determine the impact of the <i>DNAI1</i> gene on a cohort of unrelated PCD patients (n = 104) recruited without any phenotypic preselection. <i>Methods:</i> We used denaturing high-performance liquid chromatography and sequencing to screen for mutations in the coding and splicing site sequences of the gene <i>DNAI1</i>. <i>Results:</i> Three mutations were identified: a novel missense variant (p.Glu174Lys) was found in 1 patient and 2 previously reported variants were identified (p.Trp568Ser in 1 patient and IVS1+2_3insT in 3 patients). Overall, mutations on both alleles of gene <i>DNAI1</i> were identified in only 2% of our clinically heterogeneous cohort of patients. <i>Conclusion:</i> We conclude that <i>DNAI1</i> gene mutation is not a common cause of PCD, and that major or several additional disease gene(s) still remain to be identified before a sensitive molecular diagnostic test can be developed for PCD.
DOI: 10.6084/m9.figshare.5120404.v1
title: Supplementary Material for: Recruitment and in situ Renewal Regulate Rapid Accumulation of CD11c+ Cells in the Lung following Intranasal Superantigen Challenge

description: <i>Background:</i><i> Staphylococcus</i><i>aureus</i>, a primary source of bacterial superantigen, is known to colonize the human respiratory tract and has been implicated in airway inflammation. The potential pathological effect of staphylococcal enterotoxins on the respiratory tract necessitates a detailed understanding of how they regulate innate immune cells, particularly CD11c-expressing dendritic cells (DCs). <i>Methods:</i> C57BL/6 mice were challenged intranasally with staphylococcal enterotoxin A (SEA) and at indicated time points lung tissue was perfused, digested and analyzed for CD11c+ expressing cells. <i>Results:</i> The pulmonary CD11c+ cells can be divided into two major populations based on their MHC II expression. One day following intranasal SEA challenge, there was rapid accumulation of CD11c+ cells expressing medium to high levels of MHC II. The peak accumulation of CD11c+ MHC II– population was observed 2 days after SEA challenge; however, careful examination of this cell population revealed that they were heterogeneous, being comprised of cells bearing CD3, CD19, NK1.1 and F4/80 along with varying levels of CD11c. Nevertheless, there was a 2-fold increase of CD11c+ MHC II– (CD3– CD19– NK1.1– F4/80–) cells in the lungs. <i>Conclusion:</i> The mechanism of increase in the CD11c+ MHC II– immune progenitor population was mainly due to cellular division rather than migration from blood to lung. In contrast, the early and rapid accumulation of CD11c+ MHC II<sup>hi</sup> cells, conventionally known as DCs, in the lung on day 1 was mostly due to migration from blood. Thus this study examines the pulmonary innate immune response to a powerful immune stimulus.
DOI: 10.6084/m9.figshare.5120383
title: Supplementary Material for: Estimating Relative Risks from Significant Family-Based Association Studies

description: Two approaches are described to estimate relative risks from significant family-based association studies. They can be used to obtain either point estimates or confidence regions. The approaches are evaluated by a simulation study and illustrated by application to a real data set. It is shown that both approaches largely reduce the bias in the relative risk estimates which can occur in case that the significant outcome of the study from which the relative risks are estimated is ignored.
DOI: 10.6084/m9.figshare.5120389
title: Supplementary Material for: FGF2 Signaling in Mouse Embryonic Fibroblasts Is Crucial for Self-Renewal of Embryonic Stem Cells

description: Human embryonic stem cells (hESCs) can be maintained undifferentiated (pluripotent) or differentiated to basically all functional cell types, depending on the culture conditions used. Culture of hESCs in the presence of medium conditioned by mouse embryonic fibroblasts (MEFs) can be used to keep hESCs undifferentiated. This observation suggests that MEFs produce factors required for the pluripotency of hESCs. The data presented here show that fibroblast growth factor 2 (FGF2) treatment of MEFs is crucial for the production of these factors. To identify the potential factors that are expressed in the presence of FGF2 in MEFs, a global expression profile analysis using microarrays was performed. This analysis indicated that 17 secreted factors are downregulated in the absence of FGF2. These factors include several ligands for known signaling receptors, extracellular proteases and components of the extracellular matrix, that may all be involved in signaling events. Surprisingly, we found that selective blocking of extracellular signal-regulated kinase (ERK) signaling by the MAPK/ERK kinase (MEK) inhibitor U0126 affected the expression of only some of the FGF2-regulated genes, suggesting FGF2-induced pathways that are independent of ERK signaling. It has been shown recently that activation of Activin/Nodal signaling and inhibition of bone morphogenetic protein signaling are required for the maintenance of pluripotency. Accordingly, among the 17 FGF2-regulated genes we found inhibin βB that can lead to the assembly of Activin B and gremlin 1 that codes for an antagonist of bone morphogenetic proteins. This study identifies potentially important factors involved in the maintenance of pluripotency in hESCs and may allow the development of defined culture conditions without contaminating material from animal cells.
DOI: 10.6084/m9.figshare.5120395.v1
title: Supplementary Material for: Chemokine MIP-2/CXCL2, Acting on CXCR2, Induces Motor Neuron Death in Primary Cultures

description: <i>Objectives:</i> Chemokines are implicated in many diseases of the central nervous system (CNS). Although their primary role is to induce inflammation through the recruitment of leukocytes by their chemotactic activity, they may also have direct effects on neuronal cells. We evaluated the expression of CXCR1 and CXCR2 and investigated the effect of CXCR2 activation by the agonist MIP-2 (CXCL2) on primary cultured motor neurons. To specifically assess the role of CXCR2 in the neurotoxicity induced by MIP-2, we used the CXCR1/2 inhibitor reparixin and studied the effect of the chemokine on motor neuron cultures from CXCR2-deficient mice. <i>Methods:</i> Primary motor neurons prepared from rat or mouse embryos were treated with MIP-2 and reparixin. Motor neuron viability and receptor expression were assessed by immunocytochemical techniques. <i>Results:</i> Rat primary motor neurons expressed CXCR2 receptors and recombinant rat MIP-2 induced dose-dependent neurotoxicity. This neurotoxicity was counteracted by reparixin, a specific CXCR1/2 inhibitor, and was not observed in motor neurons from CXCR2-deficient mice. <i>Conclusions:</i> CXCR2 activation might directly contribute to motor neuron degeneration. Thus, chemokines acting on CXCR2, including IL-8, may have direct pathogenic effects in CNS diseases, independent of the induction of leukocyte migration.
DOI: 10.6084/m9.figshare.5120380
title: Supplementary Material for: Review and Evaluation of Methods Correcting for Population Stratification with a Focus on Underlying Statistical Principles

description: When two or more populations have been separated by geographic or cultural boundaries for many generations, drift, spontaneous mutations, differential selection pressures and other factors may lead to allele frequency differences among populations. If these ‘parental’ populations subsequently come together and begin inter-mating, disequilibrium among linked markers may span a greater genetic distance than it typically does among populations under <i>panmixia</i> [see glossary]. This extended disequilibrium can make association studies highly effective and more economical than disequilibrium mapping in panmictic populations since less marker loci are needed to detect regions of the genome that harbor phenotype-influencing loci. However, under some circumstances, this process of intermating (as well as other processes) can produce disequilibrium between pairs of unlinked loci and thus create the possibility of confounding or spurious associations due to this <i>population stratification</i>. Accordingly, researchers are advised to employ valid statistical tests for linkage disequilibrium mapping allowing conduct of genetic association studies that control for such confounding. Many recent papers have addressed this need. We provide a comprehensive review of advances made in recent years in correcting for population stratification and then evaluate and synthesize these methods based on statistical principles such as (1) randomization, (2) conditioning on sufficient statistics, and (3) identifying whether the method is based on testing the genotype-phenotype covariance (conditional upon familial information) and/or testing departures of the marginal distribution from the expected genotypic frequencies.
DOI: 10.6084/m9.figshare.5120383.v1
title: Supplementary Material for: Estimating Relative Risks from Significant Family-Based Association Studies

description: Two approaches are described to estimate relative risks from significant family-based association studies. They can be used to obtain either point estimates or confidence regions. The approaches are evaluated by a simulation study and illustrated by application to a real data set. It is shown that both approaches largely reduce the bias in the relative risk estimates which can occur in case that the significant outcome of the study from which the relative risks are estimated is ignored.
DOI: 10.6084/m9.figshare.5120377
title: Supplementary Material for: Linkage of Pluripotent Stem Cell- Associated Transcripts to Regulatory Gene Networks

description: Knowledge of the transcriptional circuitry responsible for pluripotentiality and self-renewal in embryonic stem cells is tantamount to understanding early mammalian development and a prerequisite to determining their therapeutic potential. Various techniques have employed genomics to identify transcripts that were abundant in stem cells, in an attempt to define the molecular basis of ‘stemness’. In this study, we have extended traditional genomic analyses to identify <i>cis</i>-elements that might be implicated in the control of embryonic stem cell-restricted gene promoters. The strategy relied on the generation of a problem-specific list from serial analysis of gene expression profiles and subsequent promoter analyses to identify frameworks of multiple <i>cis</i>-elements conserved in space and orientation among genes from the problem-specific list. Subsequent experimental data suggest that 2 novel transcription factors, B-Myb and Maz, predicted from these models, are implicated either in the maintenance of the undifferentiated stem cell state or in early steps of differentiation.
DOI: 10.6084/m9.figshare.5120380.v1
title: Supplementary Material for: Review and Evaluation of Methods Correcting for Population Stratification with a Focus on Underlying Statistical Principles

description: When two or more populations have been separated by geographic or cultural boundaries for many generations, drift, spontaneous mutations, differential selection pressures and other factors may lead to allele frequency differences among populations. If these ‘parental’ populations subsequently come together and begin inter-mating, disequilibrium among linked markers may span a greater genetic distance than it typically does among populations under <i>panmixia</i> [see glossary]. This extended disequilibrium can make association studies highly effective and more economical than disequilibrium mapping in panmictic populations since less marker loci are needed to detect regions of the genome that harbor phenotype-influencing loci. However, under some circumstances, this process of intermating (as well as other processes) can produce disequilibrium between pairs of unlinked loci and thus create the possibility of confounding or spurious associations due to this <i>population stratification</i>. Accordingly, researchers are advised to employ valid statistical tests for linkage disequilibrium mapping allowing conduct of genetic association studies that control for such confounding. Many recent papers have addressed this need. We provide a comprehensive review of advances made in recent years in correcting for population stratification and then evaluate and synthesize these methods based on statistical principles such as (1) randomization, (2) conditioning on sufficient statistics, and (3) identifying whether the method is based on testing the genotype-phenotype covariance (conditional upon familial information) and/or testing departures of the marginal distribution from the expected genotypic frequencies.
DOI: 10.6084/m9.figshare.5120386
title: Supplementary Material for: Cognition in an Ever-Changing World: Climatic Variability Is Associated with Brain Size in Neotropical Parrots

description: Research on the conditions favoring the evolution of complex cognition and its underlying neural structures has increasingly stressed the role of environmental variability. These studies suggest that the ability to learn, behave flexibly and innovate would be favored under unpredictable variations in the availability of resources, as it would enable organisms to adjust to novel conditions. Despite the growing number of studies based on the idea that larger-brained organisms would be better prepared to cope with environmental challenges, direct testing of the association between brain size and environmental variability per se remains scant. Here we focus on Neotropical parrots as our model group and test the hypothesis that if relatively larger brains were favored in climatically variable environments, larger-brained species should currently tolerate a higher degree of environmental uncertainty. Although we show that there are also other factors underlying the dynamics of brain size variation in this group, our results support the hypothesis that proportionally larger-brained species are more tolerant to climatic variability, both on a temporal and spatial scale. Additionally, they suggest that the differences in relative brain size among Neotropical parrots represent multiple, recent events in the evolutionary history of the group, and are particularly tied to an increased dependence on more open and climatically unstable habitats. As this is the first study to present evidence of the link between brain size and climatic variability in birds, our findings provide a step towards understanding the potential benefits underlying variation in brain size and the maintenance of highly enlarged brains in this and other groups.
DOI: 10.6084/m9.figshare.5120374
title: Supplementary Material for: Stem Cell Research within the Priority Program 1109 of the German Research Foundation, 2001–2007

description: Medicine
DOI: 10.6084/m9.figshare.5120368
title: Supplementary Material for: Complete mitochondrial genomes of <i>Bos taurus</i> and <i>Bos indicus</i> provide new insights into intra-species variation, taxonomy and domestication

description: The taurine and zebuine cattle breeds comprise the majority of the world cattle population but their taxonomic status is still controversial. The two forms of cattle are currently classified as <i>Bos taurus </i>and <i>Bos indicus </i>species and are differentiated primarily by the presence or absence of a hump. However, these two species hybridize readily, producing fully fertile offspring. We have determined and analyzed complete <i>B. taurus </i>and <i>B. indicus </i>mitochondrial genome sequences to investigate the extent of sequence divergences and to study their taxonomic status by molecular dating. The sequences encompassed 16,338 and 16,339 nucleotides, respectively, and differed at 237 positions. Estimated divergence times indicated that the two cattle lineages separated 1.7–2.0 million years ago. Combined phylogenetic analyses of 18 new and 130 previously reported extant <i>B. taurus </i>and <i>B. indicus </i>control region sequences with data from 32 archaeological specimens of the extinct wild aurochs (<i>Bos primigenius</i>) identified four major maternal lineages. <i>B. primigenius </i>haplotypes were present in all but the <i>B. indicus </i>lineage, and one <i>B. taurus </i>sequence clustered with <i>B. primigenius </i>P haplotypes that were not previously linked with domestic cattle. The <i>B. indicus </i>cluster and a recently reported new <i>B. primigenius </i>haplotype that represents a new lineage were approximately equidistant from the <i>B. taurus </i>cluster. These data suggest domestications from several differentiated populations of <i>B. primigenius </i>and a subspecies status for taurine (<i>B. primigenius taurus</i>) and zebuine (<i>B. primigenius indicus</i>) cattle.
DOI: 10.6084/m9.figshare.5120371
title: Supplementary Material for: A BAC contig map over the proximal ∼3.3 Mb region of horse chromosome 21

description: A total of 207 BAC clones containing 155 loci were isolated and arranged into a map of linearly ordered overlapping clones over the proximal part of horse chromosome 21 (ECA21), which corresponds to the proximal half of the short arm of human chromosome 19 (HSA19p) and part of HSA5. The clones form two contigs – each corresponding to the respective human chromosomes – that are estimated to be separated by a gap of ∼200 kb. Of the 155 markers present in the two contigs, 141 (33 genes and 108 STS) were generated and mapped in this study. The BACs provide a 4–5× coverage of the region and span an estimated length of ∼3.3 Mb. The region presently contains one mapped marker per 22 kb on average, which represents a major improvement over the previous resolution of one marker per 380 kb obtained through the generation of a dense RH map for this segment. Dual color fluorescence in situ hybridization on metaphase and interphase chromosomes verified the relative order of some of the BACs and helped to orient them accurately in the contigs. Despite having similar gene order and content, the equine region covered by the contigs appears to be distinctly smaller than the corresponding region in human (3.3 Mb vs. 5.5–6 Mb) because the latter harbors a host of repetitive elements and gene families unique to humans/primates. Considering limited representation of the region in the latest version of the horse whole genome sequence EquCab2, the dense map developed in this study will prove useful for the assembly and annotation of the sequence data on ECA21 and will be instrumental in rapid search and isolation of candidate genes for traits mapped to this region.