cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5121187
title: Supplementary Material for: Polymorphisms in <i>KCNQ1</i> Are Associated with Gestational Diabetes in a Korean Population

description: <i>Background:</i> Recent genome-wide association studies in East Asians have identified polymorphisms in <i>KCNQ1</i> as new type 2 diabetes risk variants. The aim of this study was to investigate whether variants in <i>KCNQ1</i> are associated with development of gestational diabetes mellitus (GDM) and measures of oral glucose tolerance test (OGTT) at the time of diagnosis of GDM. <i>Methods:</i> Three candidate single nucleotide polymorphisms (rs2074196, rs2237892, and rs2237895) were genotyped in 869 Korean GDM women and 632 nondiabetic control subjects. Insulin resistance was estimated by homeostasis model assessment and pancreatic β-cell function by the insulinogenic index at 1 h. <i>Results:</i> rs2074196 and rs2237892 were associated with the risk of GDM (OR 1.17, 95% CI 1.01–1.36, p<i> = </i>0.039; OR 1.24, 95% CI 1.07–1.45, p<i> = </i>0.0049). Furthermore, rs2237892 and rs2237895 were nominally associated with a decreased insulinogenic index at the time of GDM diagnosis (p = 0.025 and p = 0.037), whereas no association was observed with measures of insulin resistance. <i>Conclusions:</i> The single nucleotide polymorphisms in <i>KCNQ1</i> showed a significant association with GDM in the Korean population. Although the mechanism is not yet clear, it could be possible that variants in <i>KCNQ1</i> confer a risk for GDM by altering pancreatic β-cell function.
DOI: 10.6084/m9.figshare.5121175.v1
title: Supplementary Material for: Interspecific Hybrids of <i>Hordeum marinum </i>ssp. <i>marinum </i>×<i> H. bulbosum </i>Are Mitotically Stable and Reveal No Gross Alterations in Chromatin Properties

description: Interspecific hybrids between the related wild barley species <i>Hordeum marinum</i> and <i>H. bulbosum</i> were generated and tested regarding their chromosomal stability and chromatin properties. Unlike in <i>H. vulgare</i> × <i>H. bulbosum</i> hybrid embryos, there was no effect of temperature on uniparental chromosome elimination or retention during hybrid seed development and 7 chromosomes from each parent were detected according to genomic in situ hybridization analyses. The centromere-specific histone H3 gene <i>(CENH3)</i> of both parental genomes is active in hybrid plants. Indirect immunostaining of flow-sorted 2C nuclei indicated that no major reorganization of histone H3 methylation (K4, K9 and K27), H3K9 acetylation and histone H2A ubiquitination marks or location of active RNA polymerase II sites occurred after interspecific hybridization.
DOI: 10.6084/m9.figshare.5121178
title: Supplementary Material for: Prenatal Flutamide Enhances Survival in a Myogenic Mouse Model of Spinal Bulbar Muscular Atrophy

description: <i>Background:</i> Spinal bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion mutation in the androgen receptor <i>(AR)</i> gene, and mutant AR is presumed to act in motoneurons to cause SBMA. However, we found that mice overexpressing wild-type (wt) AR solely in skeletal muscle fibers display the same androgen-dependent disease phenotype as when mutant AR is broadly expressed, challenging the assumptions that only an expanded AR can induce disease and that SBMA is strictly neurogenic. We have previously reported that AR toxicity was ligand dependent in our model, and that very few transgenic (tg) males survived beyond birth. <i>Methods:</i> We tested whether the AR antagonist flutamide could block perinatal toxicity. tg males were treated prenatally with flutamide and assessed for survival and motor behavior in adulthood. <i>Results:</i> Prenatal treatment with flutamide rescued tg male pups from perinatal death, and, as adults, such perinatally rescued tg males showed an SBMA phenotype that was comparable to that of previously described untreated tg males. Moreover, tg males carrying a mutant endogenous allele for AR – the testicular feminization mutation <i>(tfm) –</i> and thus having functional AR only in muscle fibers nevertheless displayed the same androgen-dependent disease phenotype as adults. <i>Conclusions:</i> These mice represent an excellent model to study the myogenic contribution to SBMA as they display many of the core features of disease as other mouse models. These data demonstrate that AR acting exclusively in muscle fibers is sufficient to induce SBMA symptoms and that flutamide is protective perinatally.
DOI: 10.6084/m9.figshare.5121181
title: Supplementary Material for: Genetic Differences between Five European Populations

description: <i>Aims:</i> We sought to examine the magnitude of the differences in SNP allele frequencies between five European populations (Scotland, Ireland, Sweden, Bulgaria and Portugal) and to identify the loci with the greatest differences. <i>Methods:</i> We performed a population-based genome-wide association analysis with Affymetrix 6.0 and 5.0 arrays. We used a 4 degrees of freedom χ<sup>2</sup> test to determine the magnitude of stratification for each SNP. We then examined the genes within the most stratified regions, using a highly conservative cutoff of p &lt; 10<sup>–45</sup>. <i>Results:</i> We found 40,593 SNPs which are genome-wide significantly (p ≤ 10<sup>–8</sup>) stratified between these populations. The largest differences clustered in gene ontology categories for immunity and pigmentation. Some of the top loci span genes that have already been reported as highly stratified: genes for hair color and pigmentation <i>(HERC2, EXOC2, IRF4)</i>, the LCT gene, genes involved in NAD metabolism, and in immunity (HLA and the Toll-like receptor genes TLR10, TLR1, TLR6). However, several genes have not previously been reported as stratified within European populations, indicating that they might also have provided selective advantages: several zinc finger genes, two genes involved in glutathione synthesis or function, and most intriguingly, <i>FOXP2</i>, implicated in speech development. <i>Conclusion:</i> Our analysis demonstrates that many SNPs show genome-wide significant differences within European populations and the magnitude of the differences correlate with the geographical distance. At least some of these differences are due to the selective advantage of polymorphisms within these loci.
DOI: 10.6084/m9.figshare.5121184.v1
title: Supplementary Material for: An Effective Way to Solve Equivocal Mammography Findings: The Rolled Views

description: <i>Background:</i> The aim of this study was to investigate the efficacy of the rolled views taken in craniocaudal (CC) and mediolateral oblique (MLO) projections in solving equivocal mammography findings. <i>Patients and Methods:</i> The rolled views were taken by changing the positioning of the breast but not the obliquity of the X-ray beams. The breast was rolled medially or laterally in the rolled CC view, and inferiorly or superiorly in the rolled MLO view to separate overlapping structures from each other. <i>Results:</i> We evaluated equivocal findings in 87 asymptomatic women undergoing either CC (n = 48, 55%) or MLO (n = 39, 45%) rolled views between 2001 and 2008. The rolled views were helpful in solving equivocal mammographic findings and making proper decisions on management in 85 of the 87 (97.7%) women. This technique was used for breast asymmetries in 55 of the 87 (63.2%) women, and was sufficient to directly show summation artifacts in 59 of 79 (74.6%) women. The rolled views revealed 4 intramammary lymph nodes, 2 circumscribed masses out of 6 obscured masses, 7 summation artifacts, and 2 circumscribed masses out of 9 questionable masses. <i>Conclusions:</i> The rolled view is an effective method of differentiating summation artifacts from real lesions on mammography in both the CC and the MLO view.
DOI: 10.6084/m9.figshare.5121172
title: Supplementary Material for: The Structure of Genetic Linkage Data: From LIPED to 1M SNPs

description: There are three assumptions of independence or conditional independence that underlie linkage likelihood computations on sets of related individuals. The first is the independence of meioses, which gives rise to the conditional independence of haplotypes carried by offspring, given those of their parents. The second derives from the assumption of absence of genetic interference, which gives rise to the conditional independence of inheritance vectors, given the inheritance vector at an intermediate location. The third is the assumption of independence of allelic types, at the population level, both among haplotypes of unrelated individuals and also over the loci along a given haplotype. These three assumptions have been integral to likelihood computations since the first lod scores were computed, and remain key components in analysis of modern genetic data. In this paper we trace the role of these assumptions through the history of linkage likelihood computation, through to a new framework of genetic linkage analysis in the era of dense genomic marker data.
DOI: 10.6084/m9.figshare.5121187.v1
title: Supplementary Material for: Polymorphisms in <i>KCNQ1</i> Are Associated with Gestational Diabetes in a Korean Population

description: <i>Background:</i> Recent genome-wide association studies in East Asians have identified polymorphisms in <i>KCNQ1</i> as new type 2 diabetes risk variants. The aim of this study was to investigate whether variants in <i>KCNQ1</i> are associated with development of gestational diabetes mellitus (GDM) and measures of oral glucose tolerance test (OGTT) at the time of diagnosis of GDM. <i>Methods:</i> Three candidate single nucleotide polymorphisms (rs2074196, rs2237892, and rs2237895) were genotyped in 869 Korean GDM women and 632 nondiabetic control subjects. Insulin resistance was estimated by homeostasis model assessment and pancreatic β-cell function by the insulinogenic index at 1 h. <i>Results:</i> rs2074196 and rs2237892 were associated with the risk of GDM (OR 1.17, 95% CI 1.01–1.36, p<i> = </i>0.039; OR 1.24, 95% CI 1.07–1.45, p<i> = </i>0.0049). Furthermore, rs2237892 and rs2237895 were nominally associated with a decreased insulinogenic index at the time of GDM diagnosis (p = 0.025 and p = 0.037), whereas no association was observed with measures of insulin resistance. <i>Conclusions:</i> The single nucleotide polymorphisms in <i>KCNQ1</i> showed a significant association with GDM in the Korean population. Although the mechanism is not yet clear, it could be possible that variants in <i>KCNQ1</i> confer a risk for GDM by altering pancreatic β-cell function.
DOI: 10.6084/m9.figshare.5121169
title: Supplementary Material for: Hypoxia-Ischemia Induces an Endogenous Reparative Response by Local Neural Progenitors in the Postnatal Mouse Telencephalon

description: Perinatal hypoxia-ischemia in the preterm neonate commonly results in white matter injury for which there is no specific therapy. The subventricular zone (SVZ) of the brain harbors neural stem cells and more committed progenitors including oligodendroglial progenitor cells that might serve as replacement cells for treating white matter injury. Data from rodent models suggest limited replacement of mature oligodendroglia by endogenous cells. Rare newly born mature oligodendrocytes have been reported within the striatum, corpus callosum and infarcted cortex 1 month following hypoxia-ischemia. Whether these oligodendrocytes arise in situ or emigrate from the SVZ is unknown. We used a postnatal day 9 mouse model of hypoxia-ischemia, BrdU labeling of mitotic cells, immunofluorescence and time-lapse multiphoton microscopy to determine whether hypoxia-ischemia increases production of oligodendroglial progenitors within the SVZ with emigration toward injured areas. Although cells of the oligodendroglial lineage increased in the brain ipsilateral to hypoxic-ischemic injury, they did not originate from the SVZ but rather arose within the striatum and cortex. Furthermore, they resulted from proliferation within the striatum but not within the cortex. Thus, an endogenous regenerative oligodendroglial response to postnatal hypoxia-ischemia occurs locally, with minimal long-distance contribution by cells of the SVZ.
DOI: 10.6084/m9.figshare.5121178.v1
title: Supplementary Material for: Prenatal Flutamide Enhances Survival in a Myogenic Mouse Model of Spinal Bulbar Muscular Atrophy

description: <i>Background:</i> Spinal bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion mutation in the androgen receptor <i>(AR)</i> gene, and mutant AR is presumed to act in motoneurons to cause SBMA. However, we found that mice overexpressing wild-type (wt) AR solely in skeletal muscle fibers display the same androgen-dependent disease phenotype as when mutant AR is broadly expressed, challenging the assumptions that only an expanded AR can induce disease and that SBMA is strictly neurogenic. We have previously reported that AR toxicity was ligand dependent in our model, and that very few transgenic (tg) males survived beyond birth. <i>Methods:</i> We tested whether the AR antagonist flutamide could block perinatal toxicity. tg males were treated prenatally with flutamide and assessed for survival and motor behavior in adulthood. <i>Results:</i> Prenatal treatment with flutamide rescued tg male pups from perinatal death, and, as adults, such perinatally rescued tg males showed an SBMA phenotype that was comparable to that of previously described untreated tg males. Moreover, tg males carrying a mutant endogenous allele for AR – the testicular feminization mutation <i>(tfm) –</i> and thus having functional AR only in muscle fibers nevertheless displayed the same androgen-dependent disease phenotype as adults. <i>Conclusions:</i> These mice represent an excellent model to study the myogenic contribution to SBMA as they display many of the core features of disease as other mouse models. These data demonstrate that AR acting exclusively in muscle fibers is sufficient to induce SBMA symptoms and that flutamide is protective perinatally.
DOI: 10.6084/m9.figshare.5121163
title: Supplementary Material for: Alterations in Lipid and Carbohydrate Metabolism in Patients with Classic Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

description: <i>Background:</i> Classic 21-hydroxylase deficiency (21HD) presents some traits of the metabolic syndrome. <i>Aim:</i> To characterize discrete alterations of lipid and carbohydrate metabolism in children and young adults with classic 21HD, which could predict early atherogenesis. <i>Patients and Methods:</i> Twenty-seven Caucasian patients with classic 21HD (4–31 years); 27 sex-, age- and BMI-matched controls. Clinical parameters, hormonal status and genotype were assessed in all patients. Lipid parameters, including relative (%) and absolute (mg/dl) small-dense low-density lipoproteins subfractions (sd-LDL) were measured in patients and controls. Oral glucose tolerance tests were performed in both groups. <i>Results:</i> sd-LDL (%) was significantly higher in patients than controls (39.7 ± 5.9 vs. 35.5 ± 5.7%; p = 0.008). The same applies for absolute sd-LDL (mg/dl) (42.6 ± 11.9 vs. 36.4 ± 7.5; p = 0.029). HDL-cholesterol was lower in patients (p = 0.032). Fasting glucose and insulin were significantly higher in patients. Similar differences were noticed for HOMA-IR (p = 0.001), IRI (p = 0.001) and HOMA-B (p = 0.002). IRI correlated directly and significantly with the total hydrocortisone dose and the duration of treatment. Fasting glucose correlated with absolute sd-LDL. No obvious differences were seen between clinical forms or genotype groups. <i>Conclusions:</i> Substitution therapy should be adapted particularly at young ages to prevent early atherogenesis and cardiovascular risk in later life.
DOI: 10.6084/m9.figshare.5121166
title: Supplementary Material for: Regulation of Multilineage Gene Expression and Apoptosis during in vitro Expansion of Human Bone Marrow Stromal Cells with Different Cell Culture Media

description: The aim of the present study was to analyze the effect of 3 different expansion media on the expression of marker genes of mesenchymal differentiation (bone, cartilage, fat) as well as apoptosis and senescence during repeated passaging in human bone marrow stromal cells (hBMSCs) in order to identify potential expansion strategies for the use of these cells into tissue-engineered growth of bone. Medium 1 (EGF, PDGF, low Glc, 2% FCS) was associated with the highest proliferation rate compared to medium 2 (β-mercaptoethanol, high Glc DMEM, 15% FCS) and medium 3 (low Glc DMEM, 10% FCS). Real time RT-PCR indicated the lowest levels of expression of osteonectin, core binding factor-α 1, lipoprotein lipase and cartilage oligo matrix protein in medium-1 cultures as compared to media 2 and 3. Early passages expressed higher levels of peroxisome proliferator-activator receptor-γ2 in medium 1 than in media 2 and 3, whereas no difference of Sox-9 expression was noticed among the 3 media. Expression of apoptosis- and senescence-related genes (Bax, BCL-2 and P16INK4a) exhibited the lowest level of Bax/BCL-2 ratio and P16INK4a gene expression of hBMSC in medium 1. In conclusion, the replacement of FCS by recombinant EGF and PDGF promoted rapid proliferation of hBMSCs without inducing differentiation of hBMSCs. It also inhibited expression of apoptosis-related genes and limited replicative senescence during repeated passaging. Media with the lowest possible FCS content and replacement by EGF and PDGF thus should be used for 2D culturing during expansion of hBMSCs, whereas β-mercaptoethanol and high concentrations of FCS can help to commence osteogenic differentiation.
DOI: 10.6084/m9.figshare.5121172.v1
title: Supplementary Material for: The Structure of Genetic Linkage Data: From LIPED to 1M SNPs

description: There are three assumptions of independence or conditional independence that underlie linkage likelihood computations on sets of related individuals. The first is the independence of meioses, which gives rise to the conditional independence of haplotypes carried by offspring, given those of their parents. The second derives from the assumption of absence of genetic interference, which gives rise to the conditional independence of inheritance vectors, given the inheritance vector at an intermediate location. The third is the assumption of independence of allelic types, at the population level, both among haplotypes of unrelated individuals and also over the loci along a given haplotype. These three assumptions have been integral to likelihood computations since the first lod scores were computed, and remain key components in analysis of modern genetic data. In this paper we trace the role of these assumptions through the history of linkage likelihood computation, through to a new framework of genetic linkage analysis in the era of dense genomic marker data.
DOI: 10.6084/m9.figshare.5121160
title: Supplementary Material for: Evidence for Hermaphroditism in the <i>Squalius alburnoides</i> Allopolyploid Fish Complex

description: Fish show an amazing variety of mechanisms of sex determination and modes of reproduction. Of these, simultaneous hermaphroditism has rarely been described. Here, we report a novel case of this phenomenon in adults of the <i>Squalius alburnoides</i> allopolyploid cyprinid complex. We found evidence for the simultaneous presence of mature male and female gonads on the basis of gonad gross morphology and histological analyses. Different stages of male and female germ cell maturation were identified, including motile spermatocytes. We hypothesize on the genetic and/or environmental causes of this phenomenon.
DOI: 10.6084/m9.figshare.5121169.v1
title: Supplementary Material for: Hypoxia-Ischemia Induces an Endogenous Reparative Response by Local Neural Progenitors in the Postnatal Mouse Telencephalon

description: Perinatal hypoxia-ischemia in the preterm neonate commonly results in white matter injury for which there is no specific therapy. The subventricular zone (SVZ) of the brain harbors neural stem cells and more committed progenitors including oligodendroglial progenitor cells that might serve as replacement cells for treating white matter injury. Data from rodent models suggest limited replacement of mature oligodendroglia by endogenous cells. Rare newly born mature oligodendrocytes have been reported within the striatum, corpus callosum and infarcted cortex 1 month following hypoxia-ischemia. Whether these oligodendrocytes arise in situ or emigrate from the SVZ is unknown. We used a postnatal day 9 mouse model of hypoxia-ischemia, BrdU labeling of mitotic cells, immunofluorescence and time-lapse multiphoton microscopy to determine whether hypoxia-ischemia increases production of oligodendroglial progenitors within the SVZ with emigration toward injured areas. Although cells of the oligodendroglial lineage increased in the brain ipsilateral to hypoxic-ischemic injury, they did not originate from the SVZ but rather arose within the striatum and cortex. Furthermore, they resulted from proliferation within the striatum but not within the cortex. Thus, an endogenous regenerative oligodendroglial response to postnatal hypoxia-ischemia occurs locally, with minimal long-distance contribution by cells of the SVZ.
DOI: 10.6084/m9.figshare.5121154
title: Supplementary Material for: Ein langer Weg der Professionalisierung: Die Geschichte des deutschen Psychotherapeutengesetzes

description: Vor nunmehr 11 Jahren, am 01.01.1999, trat das Psychotherapeutengesetz (PsychThG) in Kraft. Nach mehreren Jahrzehnten berufspolitischer Kontroversen war es endlich gelungen, die psychologische Psychotherapie durch Schaffung zweier neuer akademischer Heilberufe auf eine adÄquate gesetzliche Grundlage zu stellen. Dennoch war das Psychotherapeutengesetz zunÄchst sehr umstritten. Werden anlÄsslich seines 10. Geburtstages einerseits die Errungenschaften des Psychotherapeutengesetzes fÜr den Berufsstand der Psychologischen Psychotherapeuten sowie der Kinder- und Jugendlichenpsychotherapeuten gewÜrdigt, wird andererseits gerade, vor allem infolge der jÜngst verÖffentlichten Ergebnisse des Forschungsgutachtens zur Psychotherapeutenausbildung, eine Diskussion um die mÖgliche ReformbedÜrftigkeit dieses Gesetzes entfacht. Von den ersten Kassenpsychotherapien und den «Laienpsychoanalytikern» ohne Ärztlichen Grundberuf in den 1920er Jahren bis zum genannten Forschungsgutachten zur Psychotherapeutenausbildung nach dem PsychThG erfolgt in diesem Beitrag eine differenzierte Darstellung der wechselvollen (Vor-)Geschichte des PsychThG, die eng mit der wenig erforschten deutschen Psychotherapiegeschichte verwoben ist. Die Geschichte der Verhaltenstherapie in Deutschland erfÄhrt in diesem Zusammenhang eine besondere WÜrdigung.
DOI: 10.6084/m9.figshare.5121157
title: Supplementary Material for: Progressive Sensorineural Hearing Loss and Normal Vestibular Function in a Dutch DFNB7/11 Family with a Novel Mutation in <i>TMC1</i>

description: In a Dutch family with autosomal recessive hearing loss, genome-wide single-nucleotide polymorphism analysis mapped the genetic defect to the DFNB7/11 locus. A novel homozygous A-to-G change in the TMC1 gene was detected near the splice donor site of intron 19 (c.1763+3A→G) segregating with the hearing loss in this family. One of the 6 transmembrane domains and the actual TMC channel domain are predicted to be absent in the mutant protein. The sensorineural hearing impairment in this DFNB7/11 family has a postlingual onset. Audiometric analysis initially showed a steeply downward-sloping threshold configuration. The progressive phenotype in this family resembles the phenotype previously described for families with dominant TMC1 mutations (DFNA36) rather than that of families with recessive TMC1 mutations (DFNB7/11) which invariably cause severe-to-profound prelingual hearing impairment.