cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5122687
title: Supplementary Material for: Two Candidate Genes <i>(FTO</i> and <i>INSIG2)</i> for Fat Accumulation in Four Canids: Chromosome Mapping, Gene Polymorphisms and Association Studies of Body and Skin Weight of Red Foxes

description: Fat accumulation is a polygenic trait which has a significant impact on human health and animal production. Obesity is also an increasingly serious problem in dog breeding. The <i>FTO</i> and <i>INSIG2 </i>are considered as candidate genes associated with predisposition for human obesity. In this report we present a comparative genomic analysis of these 2 genes in 4 species belonging to the family Canidae – the dog and 3 species which are kept in captivity for fur production, i.e. red fox, arctic fox and Chinese raccoon dog. We cytogenetically mapped these 2 loci by FISH and compared the entire coding sequence of <i>INSIG2</i> and a fragment of the coding sequence of <i>FTO. </i>The <i>FTO</i> gene was assigned to the following chromosomes: CFA2q25 (dog), VVU2q21 (red fox), ALA8q25 (arctic fox) and NPP10q24–25 (Chinese raccoon dog), while the <i>INSIG2</i> was mapped to CFA19q17, VVU5p14, ALA24q15 and NPP9q22, respectively. Altogether, 29 SNPs were identified (16 in <i>INSIG2</i> and 13 in <i>FTO</i>) and among them 2 were missense substitutions in the dog (23C/T, Thr&gt;Met in the <i>FTO </i>gene and 40C/A, Arg&gt;Ser in <i>INSIG2</i>). The distribution of these 2 SNPs was studied in 14 dog breeds. Two synonymous SNPs, one in the <i>FTO</i> gene (–28T&gt;C in the 5′-flanking region) and one in the <i>INSIG2</i> (10175C&gt;T in intron 2), were used for the association studies in red foxes (n = 390) and suggestive evidence was observed for their association with body weight (<i>FTO</i>, p &lt; 0.08) and weight of raw skin (<i>INSIG2</i>, p &lt; 0.05). These associations indicate that both genes are potential candidates for growth or adipose tissue accumulation in canids. We also suggest that the 2 missense substitutions found in dogs should be studied in terms of genetic predisposition to obesity.
DOI: 10.6084/m9.figshare.5122690
title: Supplementary Material for: Fast Approach for Clarification of Chromosomal Aberrations by Using LM-PCR and FT-CGH in Leukaemic Sample

description: Chromosomal abnormalities, like deletions, amplifications, inversions or translocations, are recurrent features in haematological malignancies. However, the precise molecular breakpoints are frequently not determined. Here we describe a rapid analysis of genetic imbalances combining fine tiling comparative genomic hybridization (FT-CGH) and ligation-mediated PCR (LM-PCR). We clarified an inv(14)(q11q32) in a case of T cell acute lymphoblastic leukaemia with a breakpoint in the <i>TRA/D</i> in 68% of cells detected by fluorescence in situ hybridization. FT-CGH showed several mono- and biallelic losses within <i>TRA/D</i>. LM-PCR disclosed a <i>TRA/D</i> rearrangement on one allele. The other allele revealed an inv(14)(q11q32), joining <i>TRDD2</i> at 21,977,000 of 14q11 together with the <i>IGH</i> locus at 105,948,000 and 3′-sequence of <i>TRAC</i> at 22,092,000 joined together with <i>IGHV4–61</i> at 106,166,000. This sensitive approach can unravel complex chromosomal abnormalities in patient samples with a limited amount of aberrant cells and may lead to better diagnostic and therapeutic options.
DOI: 10.6084/m9.figshare.5122699.v1
title: Supplementary Material for: Power of Data Mining Methods to Detect Genetic Associations and Interactions

description: <i>Background:</i> Genetic association studies, thus far, have focused on the analysis of individual main effects of SNP markers. Nonetheless, there is a clear need for modeling epistasis or gene-gene interactions to better understand the biologic basis of existing associations. Tree-based methods have been widely studied as tools for building prediction models based on complex variable interactions. An understanding of the power of such methods for the discovery of genetic associations in the presence of complex interactions is of great importance. Here, we systematically evaluate the power of three leading algorithms: random forests (RF), Monte Carlo logic regression (MCLR), and multifactor dimensionality reduction (MDR). <i>Methods:</i> We use the algorithm-specific variable importance measures (VIMs) as statistics and employ permutation-based resampling to generate the null distribution and associated p values. The power of the three is assessed via simulation studies. Additionally, in a data analysis, we evaluate the associations between individual SNPs in pro-inflammatory and immunoregulatory genes and the risk of non-Hodgkin lymphoma. <i>Results:</i> The power of RF is highest in all simulation models, that of MCLR is similar to RF in half, and that of MDR is consistently the lowest. <i>Conclusions:</i> Our study indicates that the power of RF VIMs is most reliable. However, in addition to tuning parameters, the power of RF is notably influenced by the type of variable (continuous vs. categorical) and the chosen VIM.
DOI: 10.6084/m9.figshare.5122678
title: Supplementary Material for: Application of Beta Regression to Analyze Ischemic Stroke Volume in NINDS rt-PA Clinical Trials

description: <i>Background and Purpose:</i> Ischemic stroke lesion volumes have proven difficult to analyze due to the extremely skewed shape of their underlying distribution. We introduce an extension of generalized linear models, beta regression, as a possible method of modeling extremely skewed distributions as evidenced in ischemic stroke lesion volumes. <i>Methods:</i> The NINDS rt-PA clinical trials measured ischemic stroke lesion volume as a secondary trial outcome. Three-month lesion volumes from these trials were analyzed using beta regression. A multi-variable regression model associating explanatory variables with ischemic stroke lesion volumes was constructed using accepted model building strategies and compared with the previously published volumetric analysis. <i>Results:</i> Beta regression produced a similar model when compared to the previous analysis published by the study group. All previously identified variables of importance were detected in the model building process. The age by treatment interaction described in previous studies was also found in this analysis, confirming the strong effect age has on stroke outcomes. Further, a treatment effect was elicited in terms of odds ratios, yielding a previously unknown quantification of the effect of rt-PA on lesion volumes. <i>Conclusions:</i> Beta regression proved adept in modeling ischemic stroke lesions and offered the interpretation of covariates in terms of odds ratios. Beta regression is seen as a legitimate alternative to analyze ischemic stroke volumes.
DOI: 10.6084/m9.figshare.5122681
title: Supplementary Material for: Assessment of Fetal Myocardial Deformation Using Speckle Tracking Techniques

description: <b><i>Objective:</i></b> To report the current status of speckle tracking techniques in evaluation of fetal myocardial deformation. <b><i>Methods:</i></b> A variety of non-Doppler ultrasound methods are available using offline analysis of standard four-chamber and short axis views of the heart. <b><i>Results:</i></b> Most reports have used techniques developed for the measurement of strain and strain rate in the adult heart and produced conflicting descriptions of gestational changes in strain. Myocardial velocities usually reflect mean modal velocities and are lower than the peak velocities obtained using Doppler techniques. <b><i>Conclusions:</i></b> In the fetus, most current methods of acquisition result in frame rates that are too low, and the fetal heart size is too small to achieve reliable measures of fetal myocardial deformation.
DOI: 10.6084/m9.figshare.5122684
title: Supplementary Material for: Kainate Receptors Mediate Regulated Exocytosis of Secretory Phospholipase A2 in SH-SY5Y Neuroblastoma Cells

description: Secretory phospholipase A<sub>2</sub> (sPLA<sub>2</sub>) isoforms are widely expressed in the brain and spinal cord. Group IIA sPLA<sub>2</sub> (sPLA<sub>2</sub>-IIA) has been shown to stimulate exocytosis and release of neurotransmitters in neuroendocrine PC12 cells and neurons, suggesting a role of the enzyme in neuronal signaling and synaptic transmission. However, the mechanisms by which sPLA<sub>2</sub> is itself released, and a possible relation between glutamate receptors and sPLA<sub>2</sub> exocytosis, are unknown. This study was carried out to elucidate the effects of glutamate receptor agonists on exocytosis of sPLA<sub>2</sub>-IIA in transfected SH-SY5Y neuroblastoma cells. sPLA<sub>2</sub>-IIA enzyme was packaged in fusion-competent vesicles and released constitutively or upon stimulation, suggesting regulated secretion. The signal peptide of sPLA<sub>2</sub>-IIA is required for its vesicular localization and exocytosis. External application of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) induced vesicular exocytosis and release of sPLA<sub>2</sub>-IIA. UBP 302, a GluR5-specific KA receptor antagonist, abolished the effect of KA, confirming the role of KA receptors in mediating sPLA<sub>2</sub>-IIA secretion. Moreover, KA-induced sPLA<sub>2</sub>-IIA secretion is dependent on Ca<sup>2+</sup> and protein kinase C. Together, these findings provide evidence of a link between glutamate receptors and regulated sPLA<sub>2</sub> secretion in neurons that may play an important role in synaptic plasticity, pain transmission and neurodegenerative diseases.
DOI: 10.6084/m9.figshare.5122687.v1
title: Supplementary Material for: Two Candidate Genes <i>(FTO</i> and <i>INSIG2)</i> for Fat Accumulation in Four Canids: Chromosome Mapping, Gene Polymorphisms and Association Studies of Body and Skin Weight of Red Foxes

description: Fat accumulation is a polygenic trait which has a significant impact on human health and animal production. Obesity is also an increasingly serious problem in dog breeding. The <i>FTO</i> and <i>INSIG2 </i>are considered as candidate genes associated with predisposition for human obesity. In this report we present a comparative genomic analysis of these 2 genes in 4 species belonging to the family Canidae – the dog and 3 species which are kept in captivity for fur production, i.e. red fox, arctic fox and Chinese raccoon dog. We cytogenetically mapped these 2 loci by FISH and compared the entire coding sequence of <i>INSIG2</i> and a fragment of the coding sequence of <i>FTO. </i>The <i>FTO</i> gene was assigned to the following chromosomes: CFA2q25 (dog), VVU2q21 (red fox), ALA8q25 (arctic fox) and NPP10q24–25 (Chinese raccoon dog), while the <i>INSIG2</i> was mapped to CFA19q17, VVU5p14, ALA24q15 and NPP9q22, respectively. Altogether, 29 SNPs were identified (16 in <i>INSIG2</i> and 13 in <i>FTO</i>) and among them 2 were missense substitutions in the dog (23C/T, Thr&gt;Met in the <i>FTO </i>gene and 40C/A, Arg&gt;Ser in <i>INSIG2</i>). The distribution of these 2 SNPs was studied in 14 dog breeds. Two synonymous SNPs, one in the <i>FTO</i> gene (–28T&gt;C in the 5′-flanking region) and one in the <i>INSIG2</i> (10175C&gt;T in intron 2), were used for the association studies in red foxes (n = 390) and suggestive evidence was observed for their association with body weight (<i>FTO</i>, p &lt; 0.08) and weight of raw skin (<i>INSIG2</i>, p &lt; 0.05). These associations indicate that both genes are potential candidates for growth or adipose tissue accumulation in canids. We also suggest that the 2 missense substitutions found in dogs should be studied in terms of genetic predisposition to obesity.
DOI: 10.6084/m9.figshare.5122681.v1
title: Supplementary Material for: Assessment of Fetal Myocardial Deformation Using Speckle Tracking Techniques

description: <b><i>Objective:</i></b> To report the current status of speckle tracking techniques in evaluation of fetal myocardial deformation. <b><i>Methods:</i></b> A variety of non-Doppler ultrasound methods are available using offline analysis of standard four-chamber and short axis views of the heart. <b><i>Results:</i></b> Most reports have used techniques developed for the measurement of strain and strain rate in the adult heart and produced conflicting descriptions of gestational changes in strain. Myocardial velocities usually reflect mean modal velocities and are lower than the peak velocities obtained using Doppler techniques. <b><i>Conclusions:</i></b> In the fetus, most current methods of acquisition result in frame rates that are too low, and the fetal heart size is too small to achieve reliable measures of fetal myocardial deformation.
DOI: 10.6084/m9.figshare.5122684.v1
title: Supplementary Material for: Kainate Receptors Mediate Regulated Exocytosis of Secretory Phospholipase A2 in SH-SY5Y Neuroblastoma Cells

description: Secretory phospholipase A<sub>2</sub> (sPLA<sub>2</sub>) isoforms are widely expressed in the brain and spinal cord. Group IIA sPLA<sub>2</sub> (sPLA<sub>2</sub>-IIA) has been shown to stimulate exocytosis and release of neurotransmitters in neuroendocrine PC12 cells and neurons, suggesting a role of the enzyme in neuronal signaling and synaptic transmission. However, the mechanisms by which sPLA<sub>2</sub> is itself released, and a possible relation between glutamate receptors and sPLA<sub>2</sub> exocytosis, are unknown. This study was carried out to elucidate the effects of glutamate receptor agonists on exocytosis of sPLA<sub>2</sub>-IIA in transfected SH-SY5Y neuroblastoma cells. sPLA<sub>2</sub>-IIA enzyme was packaged in fusion-competent vesicles and released constitutively or upon stimulation, suggesting regulated secretion. The signal peptide of sPLA<sub>2</sub>-IIA is required for its vesicular localization and exocytosis. External application of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) induced vesicular exocytosis and release of sPLA<sub>2</sub>-IIA. UBP 302, a GluR5-specific KA receptor antagonist, abolished the effect of KA, confirming the role of KA receptors in mediating sPLA<sub>2</sub>-IIA secretion. Moreover, KA-induced sPLA<sub>2</sub>-IIA secretion is dependent on Ca<sup>2+</sup> and protein kinase C. Together, these findings provide evidence of a link between glutamate receptors and regulated sPLA<sub>2</sub> secretion in neurons that may play an important role in synaptic plasticity, pain transmission and neurodegenerative diseases.
DOI: 10.6084/m9.figshare.5122690.v1
title: Supplementary Material for: Fast Approach for Clarification of Chromosomal Aberrations by Using LM-PCR and FT-CGH in Leukaemic Sample

description: Chromosomal abnormalities, like deletions, amplifications, inversions or translocations, are recurrent features in haematological malignancies. However, the precise molecular breakpoints are frequently not determined. Here we describe a rapid analysis of genetic imbalances combining fine tiling comparative genomic hybridization (FT-CGH) and ligation-mediated PCR (LM-PCR). We clarified an inv(14)(q11q32) in a case of T cell acute lymphoblastic leukaemia with a breakpoint in the <i>TRA/D</i> in 68% of cells detected by fluorescence in situ hybridization. FT-CGH showed several mono- and biallelic losses within <i>TRA/D</i>. LM-PCR disclosed a <i>TRA/D</i> rearrangement on one allele. The other allele revealed an inv(14)(q11q32), joining <i>TRDD2</i> at 21,977,000 of 14q11 together with the <i>IGH</i> locus at 105,948,000 and 3′-sequence of <i>TRAC</i> at 22,092,000 joined together with <i>IGHV4–61</i> at 106,166,000. This sensitive approach can unravel complex chromosomal abnormalities in patient samples with a limited amount of aberrant cells and may lead to better diagnostic and therapeutic options.
DOI: 10.6084/m9.figshare.5122669
title: Supplementary Material for: Prothrombotic Gene Variants and Mortality after Cerebral Ischemia of Arterial Origin

description: <i>Background:</i> Several functional prothrombotic gene variants have been associated with cerebral ischemia and myocardial infarction. We hypothesized that such gene variants may also be associated with mortality after cerebral ischemia of arterial origin because of an increased risk of fatal vascular events. <i>Methods:</i> We performed a case-control study in 316 long-term survivors and 887 patients with recent cerebral ischemia of arterial origin. False discovery rate q values were calculated to account for multiple testing. The mean duration between occurrence of cerebral ischemia and DNA collection was 16.8 years in long-term survivors and 3.2 months in recent patients. <i>Results:</i> Two of 23 variants were associated with mortality: the 95Arg allele of the coagulation factor XIII subunit B (F13B) His95Arg variant (OR, 1.5 for Arg/Arg and His/Arg vs. His/His genotype; 95% CI, 1.1–2.2, q = 0.29) and the 4G allele of the plasminogen activator inhibitor-1 (PAI-1) 4G/5G variant (OR, 1.5 for 4G/4G and 5G/4G vs. 5G/5G genotype; 95% CI, 1.1–2.0, q = 0.29). Both associations disappeared after accounting for multiple testing. Data analysis restricted to recently deceased patients (n = 133) yielded similar results. <i>Conclusions:</i> In this hospital-based study none of 23 prothrombotic gene variants were associated with long-term mortality after cerebral ischemia of arterial origin. Prothrombotic gene variants do not appear to play an important role in long-term mortality after cerebral ischemia.
DOI: 10.6084/m9.figshare.5122672
title: Supplementary Material for: Sunitinib for Asian Patients with Advanced Renal Cell Carcinoma: A Comparable Efficacy with Different Toxicity Profiles

description: <i>Objective:</i> We aimed to describe the efficacy and safety of sunitinib in unselected Korean advanced renal cell carcinoma (RCC) patients. <i>Patients and Methods:</i> From November 2005 to August 2008, 132 histologically confirmed advanced RCC patients (100 in the global expanded access program) were enrolled. Response and toxicity were assessed regularly according to the protocol. <i>Results:</i> Within this population, 82.6% had clear cell RCC, and 28.8% were treatment naïve. Patients received a median of 5 cycles of sunitinib (range 1–30), and the mean relative dose intensity was 82.0 ± 14.20 (SD). The progression-free survival (PFS) and overall survival rates were 8.2 and 23.1 months, respectively. For the 130 evaluable patients, the objective response rate was 34.1% (n = 45); 44.7% (n = 59) exhibited stable disease. Reasons for discontinuation were disease progression (75.0%) and toxicity (7.6%). The most frequent adverse events were thrombocytopenia (75.0%), neutropenia (70.5%), and anemia (69.7%). Low body surface area (OR = 4.2, 95% CI 1.2–13.8, p = 0.02) and previously treated status (OR = 3.1, 95% CI 1.3–7.4, p = 0.01) were highly predictive of grade 3–4 toxicities. Based on these findings, a nomogram predicting the probability of 12-month PFS was constructed, giving a concordance index of 0.675. <i>Conclusions:</i> Despite the different toxicity profiles, maintaining adequate dose modifications and a careful follow-up enables comparable treatment outcomes for unselected Korean advanced RCC patients.
DOI: 10.6084/m9.figshare.5122675
title: Supplementary Material for: Inhibition of Microglial Activation Protects Hippocampal Neurogenesis and Improves Cognitive Deficits in a Transgenic Mouse Model for Alzheimer’s Disease

description: <b><i>Background:</i></b> Activated microglia with macrophage-like functions invade and surround β-amyloid (Aβ) plaques in Alzheimer’s disease (AD), possibly contributing to the turnover of Aβ, but they can also secrete proinflammatory factors that may be involved in the pathogenesis of AD. Microglia are known to modulate adult hippocampal neurogenesis. <b><i>Objectives/Methods:</i></b> To determine the role of microglia on neurogenesis in brains with Aβ pathology, we inhibited microglial activation with the tetracycline derivative minocycline in doubly transgenic mice expressing mutant human amyloid precursor protein (APP) and mutant human presenilin-1 (PS1). <b><i>Results:</i></b> Minocycline increased the survival of new dentate granule cells in APP/PS1 mice indicated by more BrdU+/NeuN+ cells as compared to vehicle-treated transgenic littermates, accompanied by improved behavioral performance in a hippocampus-dependent learning task. Both brain levels of Aβ and Aβ-related morphological deficits in the new neurons labeled with GFP-expressing retrovirus were unaffected in minocycline-treated mice. <b><i>Conclusions:</i></b> These results suggest a role for microglia in Aβ-related functional deficits and in suppressing the survival of new neurons, and show that modulation of microglial function with minocycline can protect hippocampal neurogenesis in the presence of Aβ pathology.
DOI: 10.6084/m9.figshare.5122678.v1
title: Supplementary Material for: Application of Beta Regression to Analyze Ischemic Stroke Volume in NINDS rt-PA Clinical Trials

description: <i>Background and Purpose:</i> Ischemic stroke lesion volumes have proven difficult to analyze due to the extremely skewed shape of their underlying distribution. We introduce an extension of generalized linear models, beta regression, as a possible method of modeling extremely skewed distributions as evidenced in ischemic stroke lesion volumes. <i>Methods:</i> The NINDS rt-PA clinical trials measured ischemic stroke lesion volume as a secondary trial outcome. Three-month lesion volumes from these trials were analyzed using beta regression. A multi-variable regression model associating explanatory variables with ischemic stroke lesion volumes was constructed using accepted model building strategies and compared with the previously published volumetric analysis. <i>Results:</i> Beta regression produced a similar model when compared to the previous analysis published by the study group. All previously identified variables of importance were detected in the model building process. The age by treatment interaction described in previous studies was also found in this analysis, confirming the strong effect age has on stroke outcomes. Further, a treatment effect was elicited in terms of odds ratios, yielding a previously unknown quantification of the effect of rt-PA on lesion volumes. <i>Conclusions:</i> Beta regression proved adept in modeling ischemic stroke lesions and offered the interpretation of covariates in terms of odds ratios. Beta regression is seen as a legitimate alternative to analyze ischemic stroke volumes.