cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5122633
title: Supplementary Material for: White Matter Protection with Insulin-Like Growth Factor 1 and Hypothermia Is Not Additive after Severe Reversible Cerebral Ischemia in Term Fetal Sheep

description: Moderate cerebral hypothermia significantly improves survival without disability from perinatal hypoxia-ischemia. However, protection is partial. Insulin-like growth factor 1 (IGF-1) plays a key role in oligodendrocyte survival and myelination. The purpose of this study was to test the hypothesis that the combination of IGF-1 plus hypothermia could reduce postischemic white matter damage compared with hypothermia alone. Unanesthetized near-term fetal sheep received 30 min of cerebral ischemia, followed by either an infusion of 3 µg of IGF-1 intracerebroventricularly from 4.5 to 5.5 h plus cooling from 5.5 to 72 h (IGF-1 + hypothermia; n = 8), vehicle infusion plus cooling from 5.5 to 72 h (vehicle + hypothermia; n = 12), sham cooling plus sham infusion (ischemia control; n = 12) or sham ischemia (n = 5). The fetal extradural temperature was reduced from 39.4 ± 0.1°C to between 30 and 33°C. White matter was assessed after 5 days. Ischemia was associated with severe loss of CNPase-positive oligodendrocytes in white matter compared with sham ischemia (380 ± 138 vs. 1,180 ± 152 cells/field; mean ± SD; p &lt; 0.001). Delayed hypothermia reduced cell loss (847 ± 297 cells/field, p &lt; 0.01, vs. ischemia control), but there was no significant difference between vehicle + hypothermia and IGF-1 + hypothermia (1,015 ± 211 cells/field; NS). Ischemia was associated with increased caspase 3 expression in white matter (216 ± 41 vs. 19 ± 18 cells/field; p &lt; 0.001). Hypothermia reduced numbers of activated caspase 3-positive cells (116 ± 81 cells/field; p &lt; 0.05), with no significant difference between vehicle + hypothermia and IGF-1 + hypothermia (91 ± 27 cells/field; NS). In conclusion, delayed cotreatment with IGF-1 plus hypothermia after ischemia was associated with an improvement in white matter damage similar to that achieved by hypothermia alone.
DOI: 10.6084/m9.figshare.5122636
title: Supplementary Material for: Effect of Rearing Temperatures during Embryonic Development on the Phenotypic Sex in Zebrafish <i>(Danio rerio)</i>

description: In zebrafish,<i> Danio rerio</i>, a polygenic pattern of sex determination or a female heterogamety with possible influences of environmental factors is assumed. The present study focuses on the effects of an elevated water temperature (35°C) during the embryonic development on sex determination in zebrafish. Eggs derived from 3 golden females were fertilized by the same mitotic gynogenetic male and exposed to a water temperature of 35°C, applied from 5 to 10 h post fertilization (hpf), from 5 to 24 hpf, and from 5 to 48 hpf, which correspond to the following developmental stages: gastrula, gastrula to segmentation, and gastrula to pharyngula stage, respectively. Hatching and survival rates decreased with increasing exposure to high water temperatures. Reductions in the hatching and survival rates were not responsible for differences in sex ratios. Accordingly, exposition of the fertilized eggs to a high temperature (35°C) leads to an increase of the male proportion from 22.0% in the controls to a balanced sex ratio (48.3, 47.5, and 52.6%) in the gastrula, segmentation, and pharyngula groups, respectively. These results prove the possibility to change the pathway of sexual determination during early embryonic stages in zebrafish by exposure to a high water temperature.
DOI: 10.6084/m9.figshare.5122639.v1
title: Supplementary Material for: Association of Primary Ovarian Insufficiency with a Specific Human Leukocyte Antigen Haplotype (A*24:02-C*03:03-B*35:01) in Japanese Women

description: Primary ovarian insufficiency (POI) is a heterogeneous condition defined by the triad of oligo/amenorrhea, elevated gonadotropins and estrogen deficiency in women under the age of 40 years. Although autoimmune abnormalities appear to be involved in the development of POI, there are only a few studies with respect to human leukocyte antigen (HLA). The objective of this study was to identify an HLA allele(s) and/or haplotype(s) constituting a susceptibility factor(s) for POI. We examined 83 Japanese women with apparently idiopathic isolated POI. For controls, Japanese HLA reference data registered in the HLA Laboratory were utilized. No significant association was found for a total of 94 alleles for HLA-A, B, C, DRB1, and DQB1 loci, after both stringent Bonferroni correction and less stringent Benjamini- Hochberg (B-H) correction for multiple comparisons. By contrast, of 86 haplotypes identified for MHC class I (HLA-A, B, and C) and 31 haplotypes detected for MHC class II (HLA-DRB1 and DQB1), a single haplotype (A*24:02-C*03:03-B*35:01) remained significant after Bonferroni and B-H corrections (frequency: 4.82% in women with POI and 1.06% in the control data; p = 0.00049). The results imply that a specific HLA haplotype (A*24:02-C*03:03-B*35:01) constitutes a susceptibility factor for apparently isolated POI in Japanese women.
DOI: 10.6084/m9.figshare.5122642.v1
title: Supplementary Material for: A Method for Generating Selective DNA Probes for the Analysis of C-Negative Regions in Human Chromosomes

description: Linker-adapter polymerase chain reaction (LA-PCR) is among the most efficient techniques for whole genome DNA amplification. The key stage in LA-PCR is the hydrolysis of a DNA sample with restriction endonucleases, and the choice of a restriction endonuclease (or several endonucleases) determines the composition of DNA probes generated in LA-PCR. Computer analysis of the localization of the restriction sites in human genome has allowed us to propose an efficient technique for generating DNA probes by LA-PCR using the restriction endonucleases <i>Hae</i>III and <i>Rsa</i>I. In silico hydrolysis of human genomic DNA with endonucleases <i>Hae</i>III and <i>Rsa</i>I demonstrate that 100- to 1,000-bp DNA fragments are more abundant in the gene-rich regions. Applying in situ hybridization to metaphase chromosomes, we demonstrated that the produced DNA probes predominantly hybridized to the C-negative chromosomal regions, whereas the FISH signal was almost absent in the C-positive regions. The described protocol for generating DNA probes may be successfully used in subsequent cytogenetic analysis of the C-negative chromosomal regions.
DOI: 10.6084/m9.figshare.5122630
title: Supplementary Material for: Usefulness of Red Cell Distribution Width in Predicting All-Cause Long-Term Mortality after Non-ST-Elevation Myocardial Infarction

description: <i>Background:</i> Red blood cell distribution width (RDW) is a strong predictor of adverse outcomes in patients with heart failure, stable coronary artery disease, stroke and acute myocardial infarction. The aim of our study was to explore the predictive value of RDW on all-cause mortality in patients with non-ST-segment elevation myocardial infarction (NSTEMI). <i>Method:</i> This observational study includes 619 NSTEMI patients, discharged from Staten Island University Hospital between September 2004 and December 2006. Patients were divided into equal RDW tertiles and survival was evaluated in each tertile. <i>Result:</i> Patients in the highest RDW tertile (RDW &gt;14) had higher in-patient (7 vs. 1%) and 4-year (30 vs. 7%) mortality rates compared to those in the lowest tertile (RDW &lt;13) (Wilcoxon χ<sup>2</sup> = 34.64, p &lt; 0.0001). After controlling for Global Registry of Acute Coronary Events risk profile scores and other confounding variables, the RDW adjusted hazard ratio for 4-year all-cause mortality increased by 1.10 for each one unit increase in RDW (confidence interval 1.004–1.213, p = 0.042). <i>Conclusion:</i> RDW is an independent predictor of all-cause long-term mortality in NSTEMI patients. Further studies are needed to clarify the mechanisms of this association between RDW and adverse outcomes in patients with coronary artery disease.
DOI: 10.6084/m9.figshare.5122627
title: Supplementary Material for: Variants of <i>HSPA1A </i>in Combination with Plasma Hsp70 and Anti-Hsp70 Antibody Levels Associated with Higher Risk of Acute Coronary Syndrome

description: <i>Objectives:</i> It was the aim of our study to investigate whether polymorphisms of <i>HSP70</i> have an affect on antigen and antibody levels in acute coronary syndrome (ACS) patients and normal controls, and the possible joint effect of variants and antigen and antibody levels on the risk of ACS. <i>Methods:</i> Three single nucleotide polymorphisms of <i>HSPA1A</i> and <i>HSPA1L</i> were evaluated in 520 ACS patients and 520 age- and sex-matched controls. Plasma extracellular Hsp70 (eHsp70) and anti-Hsp70 antibody levels were determined using ELISA. <i>Results:</i> Individuals with +190G/C (rs1043618) CC genotype in <i>HSPA1A</i> had higher levels of eHsp70 in controls and lower levels of anti-Hsp70 body in ACS, compared with +190G/C GG carriers. Significantly increased ACS risks of 2.93 and 3.53 fold were found in subjects with the +190G/C CC genotype and high eHsp70 levels or low anti-Hsp70 antibody levels, respectively. The highest risk of ACS was found in subjects with +190G/C CC genotypes, high eHsp70 and low anti-Hsp70 antibody levels compared with those in the reference group (OR = 7.57, 95% CI 3.04–18.87). <i>Conclusions:</i> The +190G/C polymorphism of <i>HSPA1A</i> may contribute to influence eHsp70 levels in controls and anti-Hsp70 antibody levels in ACS, and the +190G/C genotypes, eHsp70 and anti-Hsp70 antibody levels may have a joint effect on the risk of ACS.
DOI: 10.6084/m9.figshare.5122630.v1
title: Supplementary Material for: Usefulness of Red Cell Distribution Width in Predicting All-Cause Long-Term Mortality after Non-ST-Elevation Myocardial Infarction

description: <i>Background:</i> Red blood cell distribution width (RDW) is a strong predictor of adverse outcomes in patients with heart failure, stable coronary artery disease, stroke and acute myocardial infarction. The aim of our study was to explore the predictive value of RDW on all-cause mortality in patients with non-ST-segment elevation myocardial infarction (NSTEMI). <i>Method:</i> This observational study includes 619 NSTEMI patients, discharged from Staten Island University Hospital between September 2004 and December 2006. Patients were divided into equal RDW tertiles and survival was evaluated in each tertile. <i>Result:</i> Patients in the highest RDW tertile (RDW &gt;14) had higher in-patient (7 vs. 1%) and 4-year (30 vs. 7%) mortality rates compared to those in the lowest tertile (RDW &lt;13) (Wilcoxon χ<sup>2</sup> = 34.64, p &lt; 0.0001). After controlling for Global Registry of Acute Coronary Events risk profile scores and other confounding variables, the RDW adjusted hazard ratio for 4-year all-cause mortality increased by 1.10 for each one unit increase in RDW (confidence interval 1.004–1.213, p = 0.042). <i>Conclusion:</i> RDW is an independent predictor of all-cause long-term mortality in NSTEMI patients. Further studies are needed to clarify the mechanisms of this association between RDW and adverse outcomes in patients with coronary artery disease.
DOI: 10.6084/m9.figshare.5122636.v1
title: Supplementary Material for: Effect of Rearing Temperatures during Embryonic Development on the Phenotypic Sex in Zebrafish <i>(Danio rerio)</i>

description: In zebrafish,<i> Danio rerio</i>, a polygenic pattern of sex determination or a female heterogamety with possible influences of environmental factors is assumed. The present study focuses on the effects of an elevated water temperature (35°C) during the embryonic development on sex determination in zebrafish. Eggs derived from 3 golden females were fertilized by the same mitotic gynogenetic male and exposed to a water temperature of 35°C, applied from 5 to 10 h post fertilization (hpf), from 5 to 24 hpf, and from 5 to 48 hpf, which correspond to the following developmental stages: gastrula, gastrula to segmentation, and gastrula to pharyngula stage, respectively. Hatching and survival rates decreased with increasing exposure to high water temperatures. Reductions in the hatching and survival rates were not responsible for differences in sex ratios. Accordingly, exposition of the fertilized eggs to a high temperature (35°C) leads to an increase of the male proportion from 22.0% in the controls to a balanced sex ratio (48.3, 47.5, and 52.6%) in the gastrula, segmentation, and pharyngula groups, respectively. These results prove the possibility to change the pathway of sexual determination during early embryonic stages in zebrafish by exposure to a high water temperature.
DOI: 10.6084/m9.figshare.5122618
title: Supplementary Material for: Allergenicity and Cross-Reactivity of Booklice <i>(Liposcelis bostrichophila)</i>: A Common Household Insect Pest in Japan

description: <i>Background:</i> Booklice <i>(Liposcelis bostrichophila)</i> are a common household insect pest distributed worldwide. Particularly in Japan, they infest ‘tatami’ mats and are the most frequently detected insect among all detectable insects, present at a frequency of about 90% in dust samples. Although it has been hypothesized that they are an important indoor allergen, studies on their allergenicity have been limited. <i>Methods:</i> To clarify the allergenicity of booklice and the cross-reactivity of this insect allergen with allergens of other insects, patients sensitized to booklice were identified from 185 Japanese adults with allergic asthma using skin tests and IgE-ELISA. IgE-inhibition analysis, immunoblotting and immunoblotting-inhibition analysis were performed using sera from these patients. Allergenic proteins contributing to specific sensitization to booklice were identified by two-dimensional electrophoresis and two-dimensional immunoblotting. <i>Results:</i> The booklouse-specific IgE antibody was detected in sera from 41 patients (22% of studied patients). IgE inhibition analysis revealed that IgE reactivity to the booklouse allergen in the sera from one third of booklouse-sensitized patients was not inhibited by preincubation with extracts from any other environmental insects in this study. Immunoblotting identified a 26-kD protein from booklouse extract as the allergenic protein contributing to specific sensitization to booklice. The amino acid sequence of peptide fragments of this protein showed no homology to those of previously described allergenic proteins, indicating that this protein is a new allergen. <i>Conclusions:</i> Sensitization to booklice was relatively common and specific sensitization to this insect not related to insect panallergy was indicated in this population.
DOI: 10.6084/m9.figshare.5122624
title: Supplementary Material for: Reassessment of sst<sub>5</sub> Somatostatin Receptor Expression in Normal and Neoplastic Human Tissues Using the Novel Rabbit Monoclonal Antibody UMB-4

description: <i>Objective:</i> The frequent overexpression of somatostatin receptors (sst) in neuroendocrine tumors provides the molecular basis for the diagnostic and therapeutic application of stable somatostatin analogs. Whereas octreotide acts mainly via the sst<sub>2</sub> receptor, the novel pan-somatostatin analog pasireotide exhibits particular high affinity for the sst<sub>5</sub> receptor. To determine whether a patient is a candidate for octreotide or pasireotide therapy, it is important to evaluate the somatostatin receptor status. However, so far highly specific rabbit monoclonal antibodies have been developed for the sst<sub>2</sub> receptor only (clone UMB-1). <i>Methods:</i> Here, we have extensively characterized a novel rabbit monoclonal antibody for the human sst<sub>5</sub> receptor (clone UMB-4). In a comparative immunohistochemical study, the expression of sst<sub>5</sub> and sst<sub>2</sub> receptors was assessed using UMB-4 and UMB-1, respectively. <i>Results:</i> Western blot experiments unequivocally demonstrated that UMB-4 selectively detected its cognate sst<sub>5</sub> receptor and did not cross-react with other proteins present in crude tissue homogenates. UMB-4 yielded a highly effective immunostaining of distinct cell populations in formalin-fixed, paraffin-embedded human tissues with a predominance of plasma membrane staining. In the pituitary, sst<sub>5</sub> was present on all growth hormone (GH)- and adrenocorticotropin hormone (ACTH)-producing cells whereas sst<sub>2</sub> was only observed on a subpopulation of GH-positive cells. Consequently, sst<sub>5</sub> was detectable on the majority of GH and ACTH adenomas. In contrast, sst<sub>2</sub> was only seen on GH but not on ACTH adenomas. <i>Conclusions:</i>The rabbit monoclonal antibodies UMB-4 and UMB-1 will facilitate the assessment of the somatostatin receptor status of human tumors during routine histopathological examinations.
DOI: 10.6084/m9.figshare.5122615
title: Supplementary Material for: A Potential Role for Glucose Transporters in the Evolution of Human Brain Size

description: Differences in cognitive abilities and the relatively large brain are among the most striking differences between humans and their closest primate relatives. The energy trade-off hypothesis predicts that a major shift in energy allocation among tissues occurred during human origins in order to support the remarkable expansion of a metabolically expensive brain. However, the molecular basis of this adaptive scenario is unknown. Two glucose transporters <i>(SLC2A1</i> and <i>SLC2A4)</i> are promising candidates and present intriguing mutations in humans, resulting, respectively, in microcephaly and disruptions in whole-body glucose homeostasis. We compared <i>SLC2A1</i> and <i>SLC2A4</i> expression between humans, chimpanzees and macaques, and found compensatory and biologically significant expression changes on the human lineage within cerebral cortex and skeletal muscle, consistent with mediating an energy trade-off. We also show that these two genes are likely to have undergone adaptation and participated in the development and maintenance of a larger brain in the human lineage by modulating brain and skeletal muscle energy allocation. We found that these two genes show human-specific signatures of positive selection on known regulatory elements within their 5′-untranslated region, suggesting an adaptation of their regulation during human origins. This study represents the first case where adaptive, functional and genetic lines of evidence implicate specific genes in the evolution of human brain size.
DOI: 10.6084/m9.figshare.5122621
title: Supplementary Material for: Induction and Selection of Sox17-Expressing Endoderm Cells Generated from Murine Embryonic Stem Cells

description: Embryonic stem (ES) cells offer a valuable source for generating insulin-producing cells. However, current differentiation protocols often result in heterogeneous cell populations of various developmental stages. Here we show the activin A-induced differentiation of mouse ES cells carrying a homologous dsRed-IRES-puromycin knock-in within the <i>Sox17</i> locus into the endoderm lineage. Sox17-expressing cells were selected by fluorescence-assisted cell sorting (FACS) and characterized at the transcript and protein level. Treatment of ES cells with high concentrations of activin A for 10 days resulted in up to 19% Sox17-positive cells selected by FACS. Isolated Sox17-positive cells were characterized by defini- tive endoderm-specific Sox17/Cxcr4/Foxa2 transcripts, but lacked pluripotency-associated Oct4 mRNA and protein. The Sox17-expressing cells showed downregulation of extraembryonic endoderm (Sox7, Afp, Sdf1)-, mesoderm (Foxf1, Meox1)- and ectoderm (Pax6, NeuroD6)-specific transcripts. The presence of Hnf4α, Hes1 and Pdx1 mRNA demonstrated the expression of primitive gut/foregut cell-specific markers. Ngn3, Nkx6.1 and Nkx2.2 transcripts in Sox17-positive cells were determined as properties of pancreatic endocrine progenitors. Immunocytochemistry of activin A-induced Sox17-positive embryoid bodies revealed coexpression of Cxcr4 and Foxa2. Moreover, the histochemical demonstration of E-cadherin-, Cxcr4-, Sox9-, Hnf1β- and Ngn3-positive epithelial-like structures underlined the potential of Sox17-positive cells to further differentiate into the pancreatic lineage. By reducing the heterogeneity of the ES cell progeny, Sox17-expressing cells are a suitable model to evaluate the effects of growth and differentiation factors and of culture conditions to delineate the differentiation process for the generation of pancreatic cells in vitro.
DOI: 10.6084/m9.figshare.5122624.v1
title: Supplementary Material for: Reassessment of sst<sub>5</sub> Somatostatin Receptor Expression in Normal and Neoplastic Human Tissues Using the Novel Rabbit Monoclonal Antibody UMB-4

description: <i>Objective:</i> The frequent overexpression of somatostatin receptors (sst) in neuroendocrine tumors provides the molecular basis for the diagnostic and therapeutic application of stable somatostatin analogs. Whereas octreotide acts mainly via the sst<sub>2</sub> receptor, the novel pan-somatostatin analog pasireotide exhibits particular high affinity for the sst<sub>5</sub> receptor. To determine whether a patient is a candidate for octreotide or pasireotide therapy, it is important to evaluate the somatostatin receptor status. However, so far highly specific rabbit monoclonal antibodies have been developed for the sst<sub>2</sub> receptor only (clone UMB-1). <i>Methods:</i> Here, we have extensively characterized a novel rabbit monoclonal antibody for the human sst<sub>5</sub> receptor (clone UMB-4). In a comparative immunohistochemical study, the expression of sst<sub>5</sub> and sst<sub>2</sub> receptors was assessed using UMB-4 and UMB-1, respectively. <i>Results:</i> Western blot experiments unequivocally demonstrated that UMB-4 selectively detected its cognate sst<sub>5</sub> receptor and did not cross-react with other proteins present in crude tissue homogenates. UMB-4 yielded a highly effective immunostaining of distinct cell populations in formalin-fixed, paraffin-embedded human tissues with a predominance of plasma membrane staining. In the pituitary, sst<sub>5</sub> was present on all growth hormone (GH)- and adrenocorticotropin hormone (ACTH)-producing cells whereas sst<sub>2</sub> was only observed on a subpopulation of GH-positive cells. Consequently, sst<sub>5</sub> was detectable on the majority of GH and ACTH adenomas. In contrast, sst<sub>2</sub> was only seen on GH but not on ACTH adenomas. <i>Conclusions:</i>The rabbit monoclonal antibodies UMB-4 and UMB-1 will facilitate the assessment of the somatostatin receptor status of human tumors during routine histopathological examinations.