cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5123110
title: Supplementary Material for: Arginine and Asymmetric Dimethylarginine in Puromycin Aminonucleoside-Induced Chronic Kidney Disease in the Rat

description: <i>Background/Aims:</i> Reduced renal <i>L</i>-arginine (<i>L</i>-Arg) synthesis/transport, induction of arginases and increased endogenous NOS inhibitor, asymmetric dimethylarginine (ADMA) will inhibit NO production. This study investigated pathways of <i>L</i>-Arg synthesis/uptake/utilization, ADMA degradation and oxidant/antioxidants in puromycin aminonucleoside (PAN) chronic kidney disease (CKD). <i>Methods:</i> Rats were given low- (LD) or high-dose (HD) PAN and followed for 11 weeks for proteinuria. BP was measured and blood and tissues were harvested and analyzed for abundance of argininosuccinate synthase (ASS) and lyase (ASL), arginase, cationic amino acid transporter (CAT1) and dimethylargininedimethylaminohydrolase (DDAH) in kidney, cortex, aorta and liver. Arginase and DDAH activity, plasma <i>L</i>-Arg and ADMA, renal pathology and creatinine clearances were also measured. <i>Results:</i> PAN caused dose-dependent kidney damage and hypertension and creatinine clearance fell in HD-PAN. Renal ASS fell in HD-PAN, renal cortex and aortic ASL and membrane CAT1 fell in both PAN groups. There was no activation of renal arginase, but aortic arginase increased in LD-PAN. Renal DDAH activity fell moderately in LD-PAN and markedly in HD-PAN where hepatic DDAH activity also fell. Plasma <i>L</i>-Arg was unchanged while ADMA rose moderately and dose-dependently with PAN. There were several indices of oxidative stress which was most prominent in HD-PAN. <i>Conclusion:</i> Reduction in renal ASS/ASL and loss of renal cortex CAT1 compromises renal <i>L</i>-Arg synthesis and release. Loss of aortic CAT1 impairs <i>L</i>-Arg uptake. Increased plasma ADMA was associated with progressive loss of renal DDAH activity. However, loss of renal clearance and falls in hepatic DDAH activity in HD-PAN did not have additive effects on plasma ADMA.
DOI: 10.6084/m9.figshare.5123113
title: Supplementary Material for: Exogenous Fibroblast Growth Factor-10 Induces Cystic Lung Development with Altered Target Gene Expression in the Presence of Heparin in Cultures of Embryonic Rat Lung

description: <i>Objectives:</i> Signaling by fibroblast growth factor (FGF) receptor (FGFR) 2IIIb regulates branching morphogenesis in the mammalian lung. FGFR2IIIb is primarily expressed in epithelial cells, whereas its ligands, FGF-10 and keratinocyte growth factor (KGF; FGF-7), are expressed in mesenchymal cells. <i>FGF-10</i> null mice lack lungs, whereas <i>KGF</i> null animals have normal lung development, indicating that FGF-10 regulates lung branching morphogenesis. In this study, we determined the effects of FGF-10 on lung branching morphogenesis and accompanying gene expression in cultures of embryonic rat lungs. <i>Methods:</i> Embryonic day 14 rat lungs were cultured with FGF-10 (0–250 ng/ml) in the absence or presence of heparin (30 ng/ml) for 4 days. Gene expression profiles were analyzed by Affymetrix microchip array including pathway analysis. Some of these genes, functionally important in FGF-10 signaling, were further analyzed by Northern blot, real-time PCR, in situ hybridization and immunohistochemistry. <i>Results:</i> Exogenous FGF-10 inhibited branching and induced cystic lung growth only in cultures containing heparin. In total, 252 upregulated genes and 164 downregulated genes were identified, and these included <i>Spry1</i> (Sprouty-1), <i>Spry2</i> (Sprouty-2), <i>Spred-1</i>, <i>Bmp4</i> (bone morphogenetic protein-4, BMP-4), <i>Shh </i>(sonic hedgehog, SHH), <i>Pthlh</i> (parathyroid hormone-related protein, PTHrP), <i>Dusp6</i> (MAP kinase phosphatase-3, MKP-3) and <i>Clic4</i> (chloride intracellular channel-4, CLIC-4) among the upregulated genes and <i>Igf1</i> (insulin-like growth factor-1, IGF-1), <i>Tcf21</i> (POD), <i>Gyg1</i> (glycogenin 1), <i>Sparc</i> (secreted protein acidic and rich in cysteine, SPARC), <i>Pcolce</i> (procollagen C-endopeptidase enhancer protein, Pro CEP) and <i>Lox</i> (lysyl oxidase) among the downregulated genes. <i>Gsk3</i>β and <i>Wnt2,</i> which are involved in canonical Wnt signaling, were up- and downregulated, respectively. <i>Conclusions:</i> Unlike FGF-7, FGF-10 effects on lung branching morphogenesis are heparin-dependent. Sprouty-2, BMP-4, SHH, IGF-1, SPARC and POD are known to regulate branching morphogenesis; however, potential roles of CLIC-4 and MKP-3 in lung branching morphogenesis remain to be investigated. FGF-10 may also function in regulating branching morphogenesis or inducing cystic lung growth by inhibiting Wnt2/β-catenin signaling.
DOI: 10.6084/m9.figshare.5123116
title: Supplementary Material for: Inclusion and Exclusion in Nutrigenetics Clinical Research: Ethical and Scientific Challenges

description: <i>Background/Aims:</i> There are compelling reasons to ensure the participation of ethnic minorities and populations of all ages worldwide in nutrigenetics clinical research. If findings in such research are valid for some individuals, groups, or communities, and not for others, then ethical questions of justice – and not only issues of methodology and external validity – arise. This paper aims to examine inclusion in nutrigenetics clinical research and its scientific and ethical challenges. <i>Methods:</i> In total, 173 publications were identified through a systematic review of clinical studies in nutrigenetics published between 1998 and 2007. Data such as participants’ demographics as well as eligibility criteria were extracted. <i>Results:</i> There is no consistency in the way participants’ origins (ancestry, ethnicity, or race) and ages are described in publications. A vast majority of the studies identified was conducted in North America and Europe and focused on ‘white’ participants. Our results show that pregnant women (and fetuses), minors, and the elderly (≧75 years old) remain underrepresented. <i>Conclusion:</i> Representativeness in nutrigenetics research is a challenging ethical and scientific issue. Yet, if nutrigenetics is to benefit whole populations and be used in public and global health agendas, fair representation as well as clear descriptions of participants in publications are crucial.
DOI: 10.6084/m9.figshare.5123119.v1
title: Supplementary Material for: MC4R Dimerization in the Paraventricular Nucleus and GHSR/MC3R Heterodimerization in the Arcuate Nucleus: Is There Relevance for Body Weight Regulation?

description: The worldwide obesity epidemic is increasing, yet at this time, no long-acting and specific pharmaceutical therapies are available. Peripheral hormonal signals communicate metabolic status to the hypothalamus by activating their corresponding receptors in the arcuate nucleus (ARC). In this brain region, a variety of G protein-coupled receptors (GPCRs) are expressed that are potentially involved in weight regulation, but so far, the detailed function of most hypothalamic GPCRs is only partially understood. An important and underappreciated feature of GPCRs is the capacity for regulation via di- and heterodimerization. Increasing evidence implicates that heterodimerization of GPCRs results in profound functional consequences. Recently, we could demonstrate that interaction of the melanocortin 3 receptor (MC3R) and the growth hormone secretagogue receptor (GHSR)-1a results in a modulation of function in both receptors. Although the physiological role of GPCR-GPCR interaction in the hypothalamus is yet to be elucidated, this concept promises new avenues for investigation and understanding of hypothalamic functions dependent on GPCR signaling. Since GPCRs are important targets for drugs to combat many diseases, identification of heterodimers may be a prerequisite for highly specific drugs. Therefore, a detailed understanding of the mechanisms and their involvement in weight regulation is necessary. Fundamental to this understanding is the interplay of GPCR-GPCR in the hypothalamic nuclei in energy metabolism. In this review, we summarize the current knowledge on melanocortin receptors and GHSR-1a in hypothalamic weight regulation, especially as they pertain to possible drug targets. Furthermore, we include available evidence for the participation and significance of GPCR dimerization.
DOI: 10.6084/m9.figshare.5123104
title: Supplementary Material for: International Reporting Scale of <i>BCR-ABL1</i> Fusion Transcript in Chronic Myeloid Leukemia: First Report from India

description: Achieving a major molecular response (MMR) is an important predictor of progression-free survival in chronic myeloid leukemia patients treated with imatinib. This requires accurate measurement of <i>BCR-ABL1</i> transcripts normalized to a control gene, as well as defining a level (<i>BCR-ABL1</i>/control gene ratio) that will correlate with sustained clinical response. To make these measurements comparable between laboratories, an international scale (IS) is necessary. A <i>BCR-ABL1</i>/control gene ratio of 0.10% represents MMR in the IS. In collaboration with an international reference laboratory in Adelaide, S.A., Australia, we have established and validated a lab-specific conversion factor for expressing <i>BCR-ABL1</i> transcript levels in the IS. In this report, we explain the process and steps involved in obtaining a valid lab-specific conversion factor for expressing <i>BCR-ABL1</i> transcript levels in the IS.
DOI: 10.6084/m9.figshare.5123113.v1
title: Supplementary Material for: Exogenous Fibroblast Growth Factor-10 Induces Cystic Lung Development with Altered Target Gene Expression in the Presence of Heparin in Cultures of Embryonic Rat Lung

description: <i>Objectives:</i> Signaling by fibroblast growth factor (FGF) receptor (FGFR) 2IIIb regulates branching morphogenesis in the mammalian lung. FGFR2IIIb is primarily expressed in epithelial cells, whereas its ligands, FGF-10 and keratinocyte growth factor (KGF; FGF-7), are expressed in mesenchymal cells. <i>FGF-10</i> null mice lack lungs, whereas <i>KGF</i> null animals have normal lung development, indicating that FGF-10 regulates lung branching morphogenesis. In this study, we determined the effects of FGF-10 on lung branching morphogenesis and accompanying gene expression in cultures of embryonic rat lungs. <i>Methods:</i> Embryonic day 14 rat lungs were cultured with FGF-10 (0–250 ng/ml) in the absence or presence of heparin (30 ng/ml) for 4 days. Gene expression profiles were analyzed by Affymetrix microchip array including pathway analysis. Some of these genes, functionally important in FGF-10 signaling, were further analyzed by Northern blot, real-time PCR, in situ hybridization and immunohistochemistry. <i>Results:</i> Exogenous FGF-10 inhibited branching and induced cystic lung growth only in cultures containing heparin. In total, 252 upregulated genes and 164 downregulated genes were identified, and these included <i>Spry1</i> (Sprouty-1), <i>Spry2</i> (Sprouty-2), <i>Spred-1</i>, <i>Bmp4</i> (bone morphogenetic protein-4, BMP-4), <i>Shh </i>(sonic hedgehog, SHH), <i>Pthlh</i> (parathyroid hormone-related protein, PTHrP), <i>Dusp6</i> (MAP kinase phosphatase-3, MKP-3) and <i>Clic4</i> (chloride intracellular channel-4, CLIC-4) among the upregulated genes and <i>Igf1</i> (insulin-like growth factor-1, IGF-1), <i>Tcf21</i> (POD), <i>Gyg1</i> (glycogenin 1), <i>Sparc</i> (secreted protein acidic and rich in cysteine, SPARC), <i>Pcolce</i> (procollagen C-endopeptidase enhancer protein, Pro CEP) and <i>Lox</i> (lysyl oxidase) among the downregulated genes. <i>Gsk3</i>β and <i>Wnt2,</i> which are involved in canonical Wnt signaling, were up- and downregulated, respectively. <i>Conclusions:</i> Unlike FGF-7, FGF-10 effects on lung branching morphogenesis are heparin-dependent. Sprouty-2, BMP-4, SHH, IGF-1, SPARC and POD are known to regulate branching morphogenesis; however, potential roles of CLIC-4 and MKP-3 in lung branching morphogenesis remain to be investigated. FGF-10 may also function in regulating branching morphogenesis or inducing cystic lung growth by inhibiting Wnt2/β-catenin signaling.
DOI: 10.6084/m9.figshare.5123101
title: Supplementary Material for: Variability in Laboratory Immune Parameters Is Associated with Stress Hormone Receptor Polymorphisms

description: <i>Objectives:</i> Interpretation of laboratory immune data in healthy human subjects is often challenging due to wide inter-subject variability. Since endocrine and immune mediators have been mutually interlinked, a potential explanation for the significant variability seen in immune data even when controlled for technical variability and demographics is differences in the binding affinity of ligand with hormone receptors on the surface of immune cells, which can be associated with single nucleotide polymorphisms (SNP). <i>Methods:</i> We categorized immunoregulatory cellular profiles from PBMC of 207 healthy volunteers according to glucocorticoid receptor (GR: Bcl1, TthIIII, and A3669G) and β<sub>2</sub>-adrenergic receptor (β2AR: Gly16Arg and Gln27Glu) polymorphisms. Subjects were genotyped for each SNP, and Th1, Th2, Th1/Th2 ratio, regulatory T cell (T<sub>reg</sub>), Tr1, and Th3 cell numbers were assessed. Immune parameters in the SNP groups were compared to the wild type (WT). <i>Results:</i> Significant differences were observed in Th2 and the Th1/Th2 ratio for the β2AR SNP Gly16Arg. Th1, the Th1/Th2 ratio, and Tr1 differed significantly by SNP of Gln27Glu. In addition, the effect of age on Th2 and the effect of the body mass index on the Th1/Th2 ratio significantly differed across subtypes of the Gly16Arg SNP. Significant differences based on allergic status and gender were also seen for T<sub>reg</sub>, Th1, and Th2 across Gly16Arg, Gln27Glu, and TthIIII SNP. <i>Conclusions:</i> These data suggest that SNP from various components of the stress-immune network may be useful for subgrouping of immune responses to more accurately categorize psychoneuroimmunological components of stress risk in individual subjects. This approach may have significant research and clinical potential.
DOI: 10.6084/m9.figshare.5123098
title: Supplementary Material for: Submicroscopic Deletion of <i>FGFR1</i> Gene Is Recurrently Detected in Myeloid and Lymphoid Neoplasms Associated with <i>ZMYM2-FGFR1</i> Rearrangements: A Case Study

description: Medicine
DOI: 10.6084/m9.figshare.5123110.v1
title: Supplementary Material for: Arginine and Asymmetric Dimethylarginine in Puromycin Aminonucleoside-Induced Chronic Kidney Disease in the Rat

description: <i>Background/Aims:</i> Reduced renal <i>L</i>-arginine (<i>L</i>-Arg) synthesis/transport, induction of arginases and increased endogenous NOS inhibitor, asymmetric dimethylarginine (ADMA) will inhibit NO production. This study investigated pathways of <i>L</i>-Arg synthesis/uptake/utilization, ADMA degradation and oxidant/antioxidants in puromycin aminonucleoside (PAN) chronic kidney disease (CKD). <i>Methods:</i> Rats were given low- (LD) or high-dose (HD) PAN and followed for 11 weeks for proteinuria. BP was measured and blood and tissues were harvested and analyzed for abundance of argininosuccinate synthase (ASS) and lyase (ASL), arginase, cationic amino acid transporter (CAT1) and dimethylargininedimethylaminohydrolase (DDAH) in kidney, cortex, aorta and liver. Arginase and DDAH activity, plasma <i>L</i>-Arg and ADMA, renal pathology and creatinine clearances were also measured. <i>Results:</i> PAN caused dose-dependent kidney damage and hypertension and creatinine clearance fell in HD-PAN. Renal ASS fell in HD-PAN, renal cortex and aortic ASL and membrane CAT1 fell in both PAN groups. There was no activation of renal arginase, but aortic arginase increased in LD-PAN. Renal DDAH activity fell moderately in LD-PAN and markedly in HD-PAN where hepatic DDAH activity also fell. Plasma <i>L</i>-Arg was unchanged while ADMA rose moderately and dose-dependently with PAN. There were several indices of oxidative stress which was most prominent in HD-PAN. <i>Conclusion:</i> Reduction in renal ASS/ASL and loss of renal cortex CAT1 compromises renal <i>L</i>-Arg synthesis and release. Loss of aortic CAT1 impairs <i>L</i>-Arg uptake. Increased plasma ADMA was associated with progressive loss of renal DDAH activity. However, loss of renal clearance and falls in hepatic DDAH activity in HD-PAN did not have additive effects on plasma ADMA.
DOI: 10.6084/m9.figshare.5123092
title: Supplementary Material for: Effects of 22-Oxa-Calcitriol on Podocyte Injury in Adriamycin-Induced Nephrosis

description: <i>Background:</i> In various animal studies, vitamin D has been shown to have a significant effect on reduction of proteinuria and the progression of kidney disease. However, little is known on its renoprotective effect in adriamycin (ADR)-induced nephrosis mice. The present study was intended to determine the therapeutic benefit of 22-oxa-calcitriol (OCT), a vitamin D analog, in reducing proteinuria and its renoprotective effect, i.e. preventing podocyte injury on ADR-induced nephrosis mice. <i>Methods:</i> Three experimental groups were used as follows: (1) nephrosis mice, established by a single intravenous injection of ADR; (2) ADR+OCT mice, nephrosis mice treated with OCT, and (3) mice treated only with OCT as the control group. Podocyte injury was assessed by podocyte apoptosis using the TUNEL assay, podocyte counting, podocyte-specific expressed protein by immunofluorescence and Western blot analysis, and foot process effacement using electron microscopy. <i>Results:</i> Lower proteinuria was observed in ADR+OCT mice. Improvement in glomerulosclerosis and interstitial fibrosis, and prevention of glomerular hyperfiltration were observed in ADR+OCT mice. Immunofluorescence and Western blot analyses showed restoration of downregulated expression of nephrin, CD2AP and podocin. Nevertheless, dendrin expression was not restored. An insignificant reduction in podocyte numbers was found in ADR+OCT mice. Complete foot process effacement was partially prevented in ADR+OCT mice. <i>Conclusions:</i> The results indicate that OCT reduces podocyte injury and has renoprotective effects in ADR nephrosis mice.
DOI: 10.6084/m9.figshare.5123095
title: Supplementary Material for: Diagnosis of Neonatal Sepsis by Broad-Range 16S Real-Time Polymerase Chain Reaction

description: <i>Background:</i> The standard diagnostic test (blood culture) for suspected neonatal sepsis has limitations in sensitivity and specificity, and 16S polymerase chain reaction (PCR) has been suggested as a new diagnostic tool for neonatal sepsis. <i>Objectives:</i> To develop and evaluate a new real-time PCR method for detection of bacterial DNA in blood samples collected from infants with suspected neonatal sepsis. <i>Methods:</i> Immediately after blood culture, a study sample of 0.5–1.0 ml whole blood was collected and used for a novel 16S real-time PCR assay. All positive samples were sequenced. Detailed case studies were performed in all cases with conflicting results, to verify if PCR could detect pathogens in culture negative sepsis. <i>Results:</i> 368 samples from 317 infants were included. When compared with blood culture, the assay yielded a sensitivity of 79%, a specificity of 90%, a positive predictive value of 59%, and a negative predictive value of 96%. Seven of the 31 samples with a positive PCR result and a negative blood culture had definite or suspected bacterial sepsis. In five samples, PCR (but not blood culture) could detect a pathogen that was present in a blood culture collected more than 24 h prior to the PCR sample. <i>Conclusions:</i> This study presents an evaluation of a new real-time PCR technique that can detect culture-positive sepsis, and suggests that PCR has the potential to detect bacteria in culture-negative samples even after the initiation of intravenous antibiotics.
DOI: 10.6084/m9.figshare.5123101.v1
title: Supplementary Material for: Variability in Laboratory Immune Parameters Is Associated with Stress Hormone Receptor Polymorphisms

description: <i>Objectives:</i> Interpretation of laboratory immune data in healthy human subjects is often challenging due to wide inter-subject variability. Since endocrine and immune mediators have been mutually interlinked, a potential explanation for the significant variability seen in immune data even when controlled for technical variability and demographics is differences in the binding affinity of ligand with hormone receptors on the surface of immune cells, which can be associated with single nucleotide polymorphisms (SNP). <i>Methods:</i> We categorized immunoregulatory cellular profiles from PBMC of 207 healthy volunteers according to glucocorticoid receptor (GR: Bcl1, TthIIII, and A3669G) and β<sub>2</sub>-adrenergic receptor (β2AR: Gly16Arg and Gln27Glu) polymorphisms. Subjects were genotyped for each SNP, and Th1, Th2, Th1/Th2 ratio, regulatory T cell (T<sub>reg</sub>), Tr1, and Th3 cell numbers were assessed. Immune parameters in the SNP groups were compared to the wild type (WT). <i>Results:</i> Significant differences were observed in Th2 and the Th1/Th2 ratio for the β2AR SNP Gly16Arg. Th1, the Th1/Th2 ratio, and Tr1 differed significantly by SNP of Gln27Glu. In addition, the effect of age on Th2 and the effect of the body mass index on the Th1/Th2 ratio significantly differed across subtypes of the Gly16Arg SNP. Significant differences based on allergic status and gender were also seen for T<sub>reg</sub>, Th1, and Th2 across Gly16Arg, Gln27Glu, and TthIIII SNP. <i>Conclusions:</i> These data suggest that SNP from various components of the stress-immune network may be useful for subgrouping of immune responses to more accurately categorize psychoneuroimmunological components of stress risk in individual subjects. This approach may have significant research and clinical potential.
DOI: 10.6084/m9.figshare.5123104.v1
title: Supplementary Material for: International Reporting Scale of <i>BCR-ABL1</i> Fusion Transcript in Chronic Myeloid Leukemia: First Report from India

description: Achieving a major molecular response (MMR) is an important predictor of progression-free survival in chronic myeloid leukemia patients treated with imatinib. This requires accurate measurement of <i>BCR-ABL1</i> transcripts normalized to a control gene, as well as defining a level (<i>BCR-ABL1</i>/control gene ratio) that will correlate with sustained clinical response. To make these measurements comparable between laboratories, an international scale (IS) is necessary. A <i>BCR-ABL1</i>/control gene ratio of 0.10% represents MMR in the IS. In collaboration with an international reference laboratory in Adelaide, S.A., Australia, we have established and validated a lab-specific conversion factor for expressing <i>BCR-ABL1</i> transcript levels in the IS. In this report, we explain the process and steps involved in obtaining a valid lab-specific conversion factor for expressing <i>BCR-ABL1</i> transcript levels in the IS.