cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5121031
title: Supplementary Material for: Effect of Chordin-Like 1 on MC3T3-E1 and Human Mesenchymal Stem Cells

description: Since the discovery that bone morphogenetic proteins (BMPs) are able to induce ectopic bone formation, considerable effort has been devoted to apply it for bone regeneration. BMP activity needs to be temporally and spatially controlled and the organism has devised ways to achieve it. Here we show that the BMP inhibitor chordin-like 1 can interfere with BMP2 signalling thereby affecting the osteogenic differentiation of MC3T3-E1 cells. Besides its function as a BMP antagonist, chordin-like 1 enhanced the proliferation of human mesenchymal stem cells (hMSCs) in a BMP2-independent manner. When MC3T3-E1 cells were exposed to recombinant chordin-like 1 there was an inhibition of alkaline phosphatase (ALP) expression, whereas in the case of hMSCs no effect was observed. However, chordin-like 1 dose-dependently increased the proliferation of hMSCs. This effect is probably BMP2 independent because the chordin-like 1 concentration that stimulates proliferation does not interfere with BMP signalling monitored by a Smad-dependent reporter gene. Our data point towards a novel, BMP-independent role of chordin-like 1 in hMSC proliferation.
DOI: 10.6084/m9.figshare.5121034
title: Supplementary Material for: The Gene-Environment Interactions in Respiratory Diseases (GEIRD) Project

description: The role of genetic and environmental factors, as well as their interaction, in the natural history of asthma, allergic rhinitis and chronic obstructive pulmonary disease (COPD) is largely unknown. This is mainly due to the lack of large-scale analytical epidemiological/genetic studies aimed at investigating these 3 respiratory conditions simultaneously. The GEIRD project is a collaborative initiative designed to collect information on biomarkers of inflammation and oxidative stress, individual and ecological exposures, diet, early-life factors, smoking habits, genetic traits and medication use in large and accurately defined series of asthma, allergic rhinitis and COPD phenotypes. It is a population-based multicase-control design, where cases and controls are identified through a 2-stage screening process (postal questionnaire and clinical examination) in pre-existing cohorts or new samples of subjects. It is aimed at elucidating the role that modifiable and genetic factors play in the occurrence, persistence, severity and control of inflammatory airway diseases, by way of the establishment of a historical multicentre standardized databank of phenotypes, contributed by and openly available to international epidemiologists. Researchers conducting population-based surveys with standardized methods may contribute to the public-domain case-control database, and use the resulting increased power to answer their own scientific questions.
DOI: 10.6084/m9.figshare.5121037
title: Supplementary Material for: Indoor Determinants of Endotoxin and Dust Mite Exposures in Hong Kong Homes with Asthmatic Children

description: <i>Background:</i> Domestic endotoxin enhances airway inflammation and increases asthma severity in Caucasian children, but little data are published on indoor endotoxin exposure in Asian countries. This study investigated house dust endotoxin and Der p 1 levels in Hong Kong families with asthmatic children, and their effects on asthma severity. <i>Methods:</i> 115 asthmatics from a pediatric clinic underwent fractional exhaled nitric oxide (FeNO) and spirometric measurements. Home visits were then made within 2 weeks, during which parents completed the International Study of Asthma and Allergies in Childhood questionnaire. Settled dust was collected from patients’ mattresses, bedroom floors and living room floors. Endotoxin and Der p 1 were measured by limulus amebocyte lysate and immunoassay, respectively. <i>Results:</i> Endotoxin was detectable in all locations from all families, whereas Der p 1 was detectable in 58–70% of indoor sites. Floors of both bedroom and living rooms had higher endotoxin but lower Der p 1 levels than mattresses (p &lt; 0.001 for both). Mattress endotoxin level correlated inversely with Der p 1 level (r = –0.308, p = 0.001). Household smoker, feather bedding and vacuum cleaning were independent determinants of indoor endotoxin. Timing of last bedding change was associated with Der p 1 levels at all sites. Mattress endotoxin level was associated with frequency of wheezing episodes (p = 0.044), but neither endotoxin nor Der p 1 was associated with FeNO and spirometric parameters. <i>Conclusions:</i> Domestic endotoxin levels are associated with frequency of wheezing episodes in asthmatic children but not their FeNO or spirometric measurements.
DOI: 10.6084/m9.figshare.5121028
title: Supplementary Material for: Effects of Antenatal Betamethasone and Dexamethasone on the Lung Expression of Vascular Endothelial Growth Factor and Alveolarization in Newborn Rats Exposed to Acute Hypoxia and Recovered in Normoxia or Hyperoxia

description: The use of antenatal corticosteroids is widespread and it is important to know their effect(s) on vascular endothelial growth factor (VEGF), which plays a crucial role in pulmonary development. The purpose of this study was to compare pulmonary VEGF expression in newborn rats that were exposed to antenatal betamethasone versus dexamethasone under normoxia, hypoxia and oxidative stress, and to evaluate its impact on alveolarization. Betamethasone, dexamethasone or equivalent saline solution (control group) was administered to pregnant rats. Newborn rats were randomized to room air, hypoxia followed by hyperoxia, or hypoxia followed by air. Pulmonary VEGF protein, VEGF mRNA, and alveolarization were evaluated at 4 days of life. Betamethasone and dexamethasone were observed to have different actions on VEGF expression with a correlation with alveolarization. Antenatal dexamethasone decreased VEGF expression, and dexamethasone and hyperoxia had an additive effect on the inhibition of VEGF with a reduction in alveolar development. Betamethasone appeared to have an effect on the induction of the expression of VEGF, and it seemed to inhibit the negative action of hyperoxia on VEGF. Moreover, betamethasone did not produce a decrease in alveolarization. Our results support the notion that betamethasone could be better than dexamethasone for antenatal lung maturation.
DOI: 10.6084/m9.figshare.5121040.v1
title: Supplementary Material for: Novel Adenovirus Vectors ‘Capsid-Displaying’ a Human Complement Inhibitor

description: Adenovirus (Ad) vectors are currently the most commonly utilized gene transfer vectors in humans worldwide. Unfortunately, upon contact with the circulatory system, Ads induce several, innate, complement-dependent toxicities that limit the full potential for Ad-based gene transfer applications. Therefore, we have constructed several novel Ad5-based vectors, ‘capsid-displaying’ as fiber or pIX fusion proteins, a complement-regulatory peptide (COMPinh). These novel Ads dramatically minimize Ad-dependent activation of the human and non-human primate complement systems, as determined by several assays. In summary, our work has shown that a novel COMPinh-displaying Ad5 has the potential for broadening the safe use of Ad vectors in future human applications.
DOI: 10.6084/m9.figshare.5121022
title: Supplementary Material for: Bromocriptine and Dopamine Mediate Independent and Synergistic Apoptotic Pathways in Pituitary Cells

description: Dopamine (DA) agonists are the primary treatment choice for prolactinoma, effectively suppressing prolactin expression and reducing tumour size. However, the intracellular pathway(s) through which either DA or its agonists impact on proliferation or lead to tumour shrinkage are incompletely understood. To identify the mediators in the apoptotic cascades after DA or DA agonist challenges we used a well-characterized model system, the rodent somatolactotroph cell line GH3. In these cells, we show that apoptosis induced by the DA agonist bromocriptine (BC), but not DA, is initiated through activation of the JNK pathway. However, both DA and BC activate the terminal effector caspase, caspase-3. Kinetic studies and chemical inhibitor co-incubation experiments support a role for JNK activation preceding caspase-9 activation in BC challenged cells, however, engagement of these mediators was not apparent in DA challenge cells. These studies suggest that apoptosis induced by BC or DA is mediated through distinct and independent pathways that converge with activation of the terminal caspase, caspase-3. These observations were further reinforced by our findings that DA and BC, in co-incubation experiments, synergistically induce apoptosis. These findings raise the possibility that drugs acting through the same pathway as DA may be clinically beneficial when combined with BC.
DOI: 10.6084/m9.figshare.5121025
title: Supplementary Material for: Severe Progressive Autism Associated with Two de novo Changes: A 2.6-Mb 2q31.1 Deletion and a Balanced t(14;21)(q21.1;p11.2) Translocation with Long-Range Epigenetic Silencing of <i>LRFN5</i> Expression

description: In a 19-year-old severely autistic and mentally retarded girl, a balanced de novo t(14;21)(q21.1;p11.2) translocation was found in addition to a de novo 2.6-Mb 2q31.1 deletion containing 15 protein-encoding genes. To investigate if the translocation might contribute to developmental stagnation at the age of 2 years with later regression of skills, i.e. a more severe phenotype than expected from the 2q31.1 deletion, the epigenetic status and expression of genes proximal and distal to the 14q21.1 breakpoint were investigated in Ebstein Barr Virus-transformed lymphoblast and primary skin fibroblast cells. The 14q21.1 breakpoint was found to be located between a cluster of 7 genes 0.1 Mb upstream, starting with <i>FBXO33</i>, and the single and isolated <i>LRFN5</i> gene 2.1 Mb downstream. Only expression of <i>LRFN5</i> appeared to be affected by its novel genomic context. In patient fibroblasts, <i>LRFN5</i> expression was 10-fold reduced compared to <i>LRFN5</i> expressed in control fibroblasts. In addition, a relative increase in trimethylated histone H3 lysine 9 (H3K9M3)-associated DNA starting exactly at the translocation breakpoint and going 2.5 Mb beyond the <i>LRFN5</i> gene was found. At the <i>LRFN5</i> promoter, there was a distinct peak of trimethylated histone H3 lysine 27 (H3K27M3)-associated DNA in addition to a diminished trimethylated histone H3 lysine 4 (H3K4M3) level. We speculate that dysregulation of <i>LRFN5</i>, a postsynaptic density-associated gene, may contribute to the patient’s autism, even though 2 other patients with 14q13.2q21.3 deletions that included <i>LRFN5</i> were not autistic. More significantly, we have shown that translocations may influence gene expression more than 2 Mb away from the translocation breakpoint.
DOI: 10.6084/m9.figshare.5121028.v1
title: Supplementary Material for: Effects of Antenatal Betamethasone and Dexamethasone on the Lung Expression of Vascular Endothelial Growth Factor and Alveolarization in Newborn Rats Exposed to Acute Hypoxia and Recovered in Normoxia or Hyperoxia

description: The use of antenatal corticosteroids is widespread and it is important to know their effect(s) on vascular endothelial growth factor (VEGF), which plays a crucial role in pulmonary development. The purpose of this study was to compare pulmonary VEGF expression in newborn rats that were exposed to antenatal betamethasone versus dexamethasone under normoxia, hypoxia and oxidative stress, and to evaluate its impact on alveolarization. Betamethasone, dexamethasone or equivalent saline solution (control group) was administered to pregnant rats. Newborn rats were randomized to room air, hypoxia followed by hyperoxia, or hypoxia followed by air. Pulmonary VEGF protein, VEGF mRNA, and alveolarization were evaluated at 4 days of life. Betamethasone and dexamethasone were observed to have different actions on VEGF expression with a correlation with alveolarization. Antenatal dexamethasone decreased VEGF expression, and dexamethasone and hyperoxia had an additive effect on the inhibition of VEGF with a reduction in alveolar development. Betamethasone appeared to have an effect on the induction of the expression of VEGF, and it seemed to inhibit the negative action of hyperoxia on VEGF. Moreover, betamethasone did not produce a decrease in alveolarization. Our results support the notion that betamethasone could be better than dexamethasone for antenatal lung maturation.
DOI: 10.6084/m9.figshare.5121019
title: Supplementary Material for: Altered Fate of Subventricular Zone Progenitor Cells and Reduced Neurogenesis following Neonatal Stroke

description: <i>Objective:</i> To investigate the effects of neonatal stroke on progenitor cells lining the lateral ventricles. <i>Methods:</i> Intraventricular injection of replication-incompetent green fluorescent protein (GFP)-expressing lentivirus was performed in postnatal day 1 (P1) rats to specifically label radial glia/type B neural stem cells and ependymal cells of the lateral ventricle. A subset of animals was exposed to transient middle cerebral artery occlusion (MCAO) at P7, with mild or moderate injury confirmed by diffusion-weighted MRI and histology. Newborn cells were identified by GFP expression, location and expression of cell type-specific markers in the striatum, cortex and olfactory bulb using confocal microscopy and systematic random sampling. <i>Results:</i> Three weeks lentiviral GFP transduction of cells in the lateral ventricle, abundant GFP-expressing neurons and glia were identified in the rostral migratory stream, olfactory bulb and striatum as expected from labeling the subventricular zone (SVZ) type B neural stem cell lineage. Two weeks following mild or severe focal stroke at P7, no GFP-expressing neurons were detected in striatum or cortex although some single-labeled doublecortin+ immature neurons were detected in the penumbra. The densities of GFP+/ glial fibrillary acidic protein (GFAP)+ astrocytes and GFP+/O4+ oligodendrocytes were reduced in the striatum following MCAO (4.8 ± 1.02 vs. 2.5 ± 0.4 cells/high-power field, HPF; p = 0.005; 2.8± 1 vs. 0.5 ± 0.2 cells/HPF, p = 0.008). Furthermore, there was a reduction of GFP+ cells in the olfactory bulb following MCAO (58.8 ± 14.9 vs. 19.6 ± 5.4 cells/HPF, p = 0.025). Finally, there was an increased percentage of GFP+/GFAP+ cells (70 vs. 50%), with a decreased proportion of GFP+/O4+ cells (14 vs. 30%) in injured animals. <i>Conclusion:</i> Neurogenesis originating from cells of the lateral ventricle, including SVZ type B cells, is significantly reduced following neonatal stroke. Furthermore, neonatal stroke disrupts gliogenesis in the striatum, decreasing overall numbers of new glia and shifting the population towards astrocytes.
DOI: 10.6084/m9.figshare.5121034.v1
title: Supplementary Material for: The Gene-Environment Interactions in Respiratory Diseases (GEIRD) Project

description: The role of genetic and environmental factors, as well as their interaction, in the natural history of asthma, allergic rhinitis and chronic obstructive pulmonary disease (COPD) is largely unknown. This is mainly due to the lack of large-scale analytical epidemiological/genetic studies aimed at investigating these 3 respiratory conditions simultaneously. The GEIRD project is a collaborative initiative designed to collect information on biomarkers of inflammation and oxidative stress, individual and ecological exposures, diet, early-life factors, smoking habits, genetic traits and medication use in large and accurately defined series of asthma, allergic rhinitis and COPD phenotypes. It is a population-based multicase-control design, where cases and controls are identified through a 2-stage screening process (postal questionnaire and clinical examination) in pre-existing cohorts or new samples of subjects. It is aimed at elucidating the role that modifiable and genetic factors play in the occurrence, persistence, severity and control of inflammatory airway diseases, by way of the establishment of a historical multicentre standardized databank of phenotypes, contributed by and openly available to international epidemiologists. Researchers conducting population-based surveys with standardized methods may contribute to the public-domain case-control database, and use the resulting increased power to answer their own scientific questions.
DOI: 10.6084/m9.figshare.5121010
title: Supplementary Material for: Substrate-Dependent Regulation of Carbon Catabolism in Marine Sulfate-Reducing <i>Desulfobacterium autotrophicum</i> HRM2

description: <i>Desulfobacterium autotrophicum</i> HRM2 is a metabolically versatile sulfate-reducing bacterium, capable of heterotrophic (e.g. with organic acids and alcohols) and chemolithoautotrophic growth (with H<sub>2</sub>/CO<sub>2</sub>). It employs the Wood-Ljungdahl pathway for complete oxidation of acetyl-CoA to CO<sub>2</sub> and for CO<sub>2</sub> fixation. Here, we investigated substrate-dependent regulation at different levels of anaerobic carbon catabolism in this bacterium. (a) Whole-cell adaptation studies indicated an inducibleutilization of short-chained alcohols, agreeing with a substrate-specific abundance increase (up to 40-fold) of alcohol dehydrogenase Adh4. Simultaneous utilization of lactate and 1-propanol was paralleled by <i>adh4</i> expression and Adh4 formation, respectively. (b) Degradation of propionate generally involves methylmalonyl-CoA mutase (Sbm). Expression of <i>sbm</i> was upregulated during growth with 1-propanol, but not with a mixture of lactate and 1-propanol. Correspondingly, propionate was excreted during growth with this substrate mixture. (c) CO dehydrogenase, the key enzyme of the Wood-Ljungdahl pathway, is encoded by several genes <i>(cdhC</i>, <i>cdh1</i> and <i>cdh2)</i> located at different genomic positions. Expression of all of these genes during heterotrophic and autotrophic growth points to a reversible operation of the Wood-Ljungdahl pathway. In summary, the different regulatory patterns displayed by <i>Db. autotrophicum</i> HRM2 at the tested metabolic levels point to a multi-layered regulatory network.
DOI: 10.6084/m9.figshare.5121016
title: Supplementary Material for: Kindesmisshandlung: Ein Abriss

description: Der Artikel gibt einen Überblick zur Entwicklung der Häufigkeitszahlen und zu den Korrelaten von Kindesmisshandlung aus der Perspektive der Kriminologie. Bedingt durch eine fortschreitende Sensibilisierung in der Bevölkerung ist unter anderem ein Rückgang gewalttätiger Erziehungsstile in den vergangenen Jahren zu konstatieren. Einen bedeutsamen Beitrag zum Umdenken und zu Verhaltensänderungen tragen hierbei legislative Änderungen und damit einhergehende öffentliche Diskurse zur Ächtung von Gewalt, insbesondere zur Ächtung von Gewalt gegen Kinder. Forschungen bestätigen, dass dies auch im Hinblick auf die Durchbrechung des Gewaltkreislaufes eine außerordentlich bedeutungsvolle Entwicklung ist.
DOI: 10.6084/m9.figshare.5121019.v1
title: Supplementary Material for: Altered Fate of Subventricular Zone Progenitor Cells and Reduced Neurogenesis following Neonatal Stroke

description: <i>Objective:</i> To investigate the effects of neonatal stroke on progenitor cells lining the lateral ventricles. <i>Methods:</i> Intraventricular injection of replication-incompetent green fluorescent protein (GFP)-expressing lentivirus was performed in postnatal day 1 (P1) rats to specifically label radial glia/type B neural stem cells and ependymal cells of the lateral ventricle. A subset of animals was exposed to transient middle cerebral artery occlusion (MCAO) at P7, with mild or moderate injury confirmed by diffusion-weighted MRI and histology. Newborn cells were identified by GFP expression, location and expression of cell type-specific markers in the striatum, cortex and olfactory bulb using confocal microscopy and systematic random sampling. <i>Results:</i> Three weeks lentiviral GFP transduction of cells in the lateral ventricle, abundant GFP-expressing neurons and glia were identified in the rostral migratory stream, olfactory bulb and striatum as expected from labeling the subventricular zone (SVZ) type B neural stem cell lineage. Two weeks following mild or severe focal stroke at P7, no GFP-expressing neurons were detected in striatum or cortex although some single-labeled doublecortin+ immature neurons were detected in the penumbra. The densities of GFP+/ glial fibrillary acidic protein (GFAP)+ astrocytes and GFP+/O4+ oligodendrocytes were reduced in the striatum following MCAO (4.8 ± 1.02 vs. 2.5 ± 0.4 cells/high-power field, HPF; p = 0.005; 2.8± 1 vs. 0.5 ± 0.2 cells/HPF, p = 0.008). Furthermore, there was a reduction of GFP+ cells in the olfactory bulb following MCAO (58.8 ± 14.9 vs. 19.6 ± 5.4 cells/HPF, p = 0.025). Finally, there was an increased percentage of GFP+/GFAP+ cells (70 vs. 50%), with a decreased proportion of GFP+/O4+ cells (14 vs. 30%) in injured animals. <i>Conclusion:</i> Neurogenesis originating from cells of the lateral ventricle, including SVZ type B cells, is significantly reduced following neonatal stroke. Furthermore, neonatal stroke disrupts gliogenesis in the striatum, decreasing overall numbers of new glia and shifting the population towards astrocytes.
DOI: 10.6084/m9.figshare.5121007
title: Supplementary Material for: Genetic Variations in the Sodium Balance-Regulating Genes <i>ENaC</i>, <i>NEDD4L</i>, <i>NDFIP2</i> and <i>USP2</i> Influence Blood Pressure and Hypertension

description: <i>Background/Aims:</i> In humans, the kidneys regulate blood pressure by balancing sodium concentrations. Fine-tuning of renal sodium reabsorption and excretion depends on the epithelial sodium channel protein (ENaC: protein complex of SCNN1A, SCNN1B, and SCNN1G). The surface expression of ENaC components is directed by the ubiquitination of ENaC by NEDD4L, an ENaC-specific E3 ubiquitin ligase, and is regulated by the deubiquitination of ENaC by USP2. The activity of NEDD4L in turn is regulated by phosphorylation by SGK1 and also through interaction with NDFIP2. <i>Methods:</i> We analyzed 91 SNPs in 7 genes using the genotype data of 8,842 individuals from the Korea Association REsource subject pool for their correlation with blood pressure and hypertension. <i>Results:</i> 25 SNPs in the <i>SCNN1A</i>, <i>SCNN1B</i>, <i>SCNN1G</i>, <i>NEDD4L</i>, <i>NDFIP2, </i>and<i> USP2 </i>loci were found to be associated with blood pressure. An additional hypertension case-control study identified 13 SNPs in <i>SCNN1B</i>, <i>SCNN1G,</i> and<i> NEDD4L</i> that were linked to hypertension. <i>Conclusion:</i> These results support our hypothesis that individual variations in blood pressure are attributed to variants of the genes that regulate renal sodium reabsorption and excretion. Our data also suggest that it would be meaningful to investigate the role of NEDD4L-mediated ubiquitination in the pathogenesis of hypertension.