cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.1282527
title: Targeting FoxO1 with AS1842856 Suppresses Adipogenesis

description: Hyperplasia (i.e., increased adipogenesis) contributes to excess adiposity, the hallmark of obesity that can trigger metabolic complications. As FoxO1 has been implicated in adipogenic regulation, we investigated the kinetics of FoxO1 activation during adipocyte differentiation, and tested the effects of FoxO1 antagonist (AS1842856) on adipogenesis. We found for the first time that the kinetics of FoxO1 activation follows a series of sigmoid curves, and reveals the phases relevant to clonal expansion, cell cycle arrest, and the regulation of PPARγ, adiponectin, and mitochondrial proteins (complexes I and III). In addition, multiple activation-inactivation transitions exist in the stage of terminal differentiation. Importantly, persistent inhibition of FoxO1 with AS1842856 almost completely suppressed adipocyte differentiation, while selective inhibition in specific stages had differential effects on adipogenesis. Our data present a new view of FoxO1 in adipogenic regulation, and suggest AS1842856 can be an anti-obesity agent that warrants further investigation.
DOI: 10.6084/m9.figshare.1282527.v2
title: Targeting FoxO1 with AS1842856 Suppresses Adipogenesis

description: Hyperplasia (i.e., increased adipogenesis) contributes to excess adiposity, the hallmark of obesity that can trigger metabolic complications. As FoxO1 has been implicated in adipogenic regulation, we investigated the kinetics of FoxO1 activation during adipocyte differentiation, and tested the effects of FoxO1 antagonist (AS1842856) on adipogenesis. We found for the first time that the kinetics of FoxO1 activation follows a series of sigmoid curves, and reveals the phases relevant to clonal expansion, cell cycle arrest, and the regulation of PPARγ, adiponectin, and mitochondrial proteins (complexes I and III). In addition, multiple activation-inactivation transitions exist in the stage of terminal differentiation. Importantly, persistent inhibition of FoxO1 with AS1842856 almost completely suppressed adipocyte differentiation, while selective inhibition in specific stages had differential effects on adipogenesis. Our data present a new view of FoxO1 in adipogenic regulation, and suggest AS1842856 can be an anti-obesity agent that warrants further investigation.
DOI: 10.6084/m9.figshare.1282527.v1
title: Targeting FoxO1 with AS1842856 Suppresses Adipogenesis

description: Hyperplasia (i.e., increased adipogenesis) contributes to excess adiposity, the hallmark of obesity that can trigger metabolic complications. As FoxO1 has been implicated in adipogenic regulation, we investigated the kinetics of FoxO1 activation during adipocyte differentiation, and tested the effects of FoxO1 antagonist (AS1842856) on adipogenesis. We found for the first time that the kinetics of FoxO1 activation follows a series of sigmoid curves, and reveals the phases relevant to clonal expansion, cell cycle arrest, and the regulation of PPARγ, adiponectin, and mitochondrial proteins (complexes I and III). In addition, multiple activation-inactivation transitions exist in the stage of terminal differentiation. Importantly, persistent inhibition of FoxO1 with AS1842856 almost completely suppressed adipocyte differentiation, while selective inhibition in specific stages had differential effects on adipogenesis. Our data present a new view of FoxO1 in adipogenic regulation, and suggest AS1842856 can be an anti-obesity agent that warrants further investigation.
DOI: 10.6084/m9.figshare.1284583
title: Original networks, NVC networks and COPD data sets used in: Enhancement of COPD biological networks using a web-based collaboration interface

description: Original networks, NVC networks and their descriptions.<br>The file contains the names of the original networks (as they were published), agglomerated NVC networks (as presented on the Bionet website), and network descriptions. The 15 networks that were discussed during jamboree are indicated by “X” in the column Discussed in Jamboree.
COPD data sets, their descriptions, and the comparisons used to build the COPD models during Phase 1.<br>Reverse causal reasoning was performed using COPD and emphysema data sets from lung, small airway, and alveolar macrophages of early COPD patients and healthy smokers. Data Sets, the Gene Expression Omnibus (GEO) used to build the COPD networks. SCs, state changes defined using differentially expressed genes that meet the following criteria: FDR adjusted p&lt;0.05, fold change ≥1.3, and minimum expression of 100 (for Affy platforms). HYPs, mechanisms or hypotheses predicted from the SCs and the Selventa Knowledgebase [1] with the following cutoffs: richness p&lt;0.1, concordance p&lt;0.1.
Early COPD was defined as Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1 and 2.<br>The three small airway data sets were merged using ComBat [2] because of the small sample size of early COPD patients within each data set.<br>Lone emphysema is defined in the GSE10006 data set as patients who have normal spirometry but decreased transfer factor and evidence of emphysema on chest computed tomography scans. The lone emphysema data were selected because they might be useful in understanding COPD onset.
References<br>1. Catlett NL, Bargnesi AJ, Ungerer S, Seagaran T, Ladd W, Elliston KO, Pratt D: Reverse causal reasoning: applying qualitative causal knowledge to the interpretation of high-throughput data. BMC bioinformatics 2013, 14:340.<br>2. Chen C, Grennan K, Badner J, Zhang D, Gershon E, Jin L, Liu C: Removing batch effects in analysis of expression microarray data: an evaluation of six batch adjustment methods. PloS one 2011, 6:e17238.
DOI: 10.6084/m9.figshare.1284583.v1
title: Original networks, NVC networks and COPD data sets used in: Enhancement of COPD biological networks using a web-based collaboration interface

description: Original networks, NVC networks and their descriptions.<br>The file contains the names of the original networks (as they were published), agglomerated NVC networks (as presented on the Bionet website), and network descriptions. The 15 networks that were discussed during jamboree are indicated by “X” in the column Discussed in Jamboree.
COPD data sets, their descriptions, and the comparisons used to build the COPD models during Phase 1.<br>Reverse causal reasoning was performed using COPD and emphysema data sets from lung, small airway, and alveolar macrophages of early COPD patients and healthy smokers. Data Sets, the Gene Expression Omnibus (GEO) used to build the COPD networks. SCs, state changes defined using differentially expressed genes that meet the following criteria: FDR adjusted p&lt;0.05, fold change ≥1.3, and minimum expression of 100 (for Affy platforms). HYPs, mechanisms or hypotheses predicted from the SCs and the Selventa Knowledgebase [1] with the following cutoffs: richness p&lt;0.1, concordance p&lt;0.1.
Early COPD was defined as Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1 and 2.<br>The three small airway data sets were merged using ComBat [2] because of the small sample size of early COPD patients within each data set.<br>Lone emphysema is defined in the GSE10006 data set as patients who have normal spirometry but decreased transfer factor and evidence of emphysema on chest computed tomography scans. The lone emphysema data were selected because they might be useful in understanding COPD onset.
References<br>1. Catlett NL, Bargnesi AJ, Ungerer S, Seagaran T, Ladd W, Elliston KO, Pratt D: Reverse causal reasoning: applying qualitative causal knowledge to the interpretation of high-throughput data. BMC bioinformatics 2013, 14:340.<br>2. Chen C, Grennan K, Badner J, Zhang D, Gershon E, Jin L, Liu C: Removing batch effects in analysis of expression microarray data: an evaluation of six batch adjustment methods. PloS one 2011, 6:e17238.
DOI: 10.6084/m9.figshare.1284992
title: Rapid separation of seed gliadins by reversed-phase ultra performance liquid chromatography (RP-UPLC) and its application in wheat cultivar and germplasm identification

description: To separate gliadin from wheat flour, a novel and stability-indicating reversed-phase ultra performance liquid chromatography (RP-UPLC) method is established and optimized. A comparative analysis of routine capillary electrophoresis (CE), reversed-phase high-performance liquid chromatography (RP-HPLC), and RP-UPLC was performed and the results showed that the resolution and efficiency of RP-UPLC were significantly higher than those of CE and RP-HPLC. Characteristic RP-UPLC patterns of different bread wheat variety and related species were readily identified. These results demonstrated that our RP-UPLC procedure resulted in significant improvements in sensitivity, speed, and resolution, and thus is highly useful in wheat cultivar and germplasm identification.
DOI: 10.6084/m9.figshare.1284992.v1
title: Rapid separation of seed gliadins by reversed-phase ultra performance liquid chromatography (RP-UPLC) and its application in wheat cultivar and germplasm identification

description: To separate gliadin from wheat flour, a novel and stability-indicating reversed-phase ultra performance liquid chromatography (RP-UPLC) method is established and optimized. A comparative analysis of routine capillary electrophoresis (CE), reversed-phase high-performance liquid chromatography (RP-HPLC), and RP-UPLC was performed and the results showed that the resolution and efficiency of RP-UPLC were significantly higher than those of CE and RP-HPLC. Characteristic RP-UPLC patterns of different bread wheat variety and related species were readily identified. These results demonstrated that our RP-UPLC procedure resulted in significant improvements in sensitivity, speed, and resolution, and thus is highly useful in wheat cultivar and germplasm identification.
DOI: 10.6084/m9.figshare.1284992.v2
title: Rapid separation of seed gliadins by reversed-phase ultra performance liquid chromatography (RP-UPLC) and its application in wheat cultivar and germplasm identification

description: To separate gliadin from wheat flour, a novel and stability-indicating reversed-phase ultra performance liquid chromatography (RP-UPLC) method is established and optimized. A comparative analysis of routine capillary electrophoresis (CE), reversed-phase high-performance liquid chromatography (RP-HPLC), and RP-UPLC was performed and the results showed that the resolution and efficiency of RP-UPLC were significantly higher than those of CE and RP-HPLC. Characteristic RP-UPLC patterns of different bread wheat variety and related species were readily identified. These results demonstrated that our RP-UPLC procedure resulted in significant improvements in sensitivity, speed, and resolution, and thus is highly useful in wheat cultivar and germplasm identification.
DOI: 10.6084/m9.figshare.1288863
title: Identification of miRNAs that modulate glucocerebrosidase activity in Gaucher disease cells

description: Gaucher disease is an autosomal recessive disorder caused by deficiency of the enzyme glucocerebrosidase. Although it is a monogenic disease, there is vast phenotypic heterogeneity, even among patients with the same genotype. MicroRNAs (miRNAs) are small non-coding RNAs involved in many biological processes and diseases. To determine whether miRNAs can affect glucocerebrosidase activity, we performed a screen of 875 different miRNA mimics. The screen was performed using Gaucher fibroblasts, and glucocerebrosidase activity was used as the initial outcome parameter. We found several miRNAs that either up- or down-regulated glucocerebrosidase activity. In follow-up assays, we confirmed that one specific miRNA (miR-127–5p) down-regulated both glucocerebrosidase activity and protein levels by down-regulation of LIMP-2, the receptor involved in proper trafficking of glucocerebrosidase from the endoplasmic reticulum to the lysosome. A conditioned media assay demonstrated that cells treated with this miRNA secreted glucocerebrosidase into the extracellular environment, supporting impaired LIMP-2 function. Two other miRNAs, miR-16–5p and miR-195–5p, were found to up-regulate glucocerebrosidase activity by greater than 40% and to enhance expression and protein levels of the enzyme. In conclusion, we show that miRNAs can alter glucocerebrosidase activity in patient cells, indicating that miRNAs can potentially act as modifiers in Gaucher disease.
DOI: 10.6084/m9.figshare.1288863.v1
title: Identification of miRNAs that modulate glucocerebrosidase activity in Gaucher disease cells

description: ABSTRACTGaucher disease is an autosomal recessive disorder caused by deficiency of the enzyme glucocerebrosidase. Although it is a monogenic disease, there is vast phenotypic heterogeneity, even among patients with the same genotype. MicroRNAs (miRNAs) are small non-coding RNAs involved in many biological processes and diseases. To determine whether miRNAs can affect glucocerebrosidase activity, we performed a screen of 875 different miRNA mimics. The screen was performed using Gaucher fibroblasts, and glucocerebrosidase activity was used as the initial outcome parameter. We found several miRNAs that either up- or down-regulated glucocerebrosidase activity. In follow-up assays, we confirmed that one specific miRNA (miR-127-5p) down-regulated both glucocerebrosidase activity and protein levels by down-regulation of LIMP-2, the receptor involved in proper trafficking of glucocerebrosidase from the endoplasmic reticulum to the lysosome. A conditioned media assay demonstrated that cells treated with this miRNA secreted glucocerebrosidase into the extracellular environment, supporting impaired LIMP-2 function. Two other miRNAs, miR-16-5p and miR-195-5p, were found to up-regulate glucocerebrosidase activity by greater than 40% and to enhance expression and protein levels of the enzyme. In conclusion, we show that miRNAs can alter glucocerebrosidase activity in patient cells, indicating that miRNAs can potentially act as modifiers in Gaucher disease.
DOI: 10.6084/m9.figshare.1288863.v3
title: Identification of miRNAs that modulate glucocerebrosidase activity in Gaucher disease cells

description: Gaucher disease is an autosomal recessive disorder caused by deficiency of the enzyme glucocerebrosidase. Although it is a monogenic disease, there is vast phenotypic heterogeneity, even among patients with the same genotype. MicroRNAs (miRNAs) are small non-coding RNAs involved in many biological processes and diseases. To determine whether miRNAs can affect glucocerebrosidase activity, we performed a screen of 875 different miRNA mimics. The screen was performed using Gaucher fibroblasts, and glucocerebrosidase activity was used as the initial outcome parameter. We found several miRNAs that either up- or down-regulated glucocerebrosidase activity. In follow-up assays, we confirmed that one specific miRNA (miR-127–5p) down-regulated both glucocerebrosidase activity and protein levels by down-regulation of LIMP-2, the receptor involved in proper trafficking of glucocerebrosidase from the endoplasmic reticulum to the lysosome. A conditioned media assay demonstrated that cells treated with this miRNA secreted glucocerebrosidase into the extracellular environment, supporting impaired LIMP-2 function. Two other miRNAs, miR-16–5p and miR-195–5p, were found to up-regulate glucocerebrosidase activity by greater than 40% and to enhance expression and protein levels of the enzyme. In conclusion, we show that miRNAs can alter glucocerebrosidase activity in patient cells, indicating that miRNAs can potentially act as modifiers in Gaucher disease.
DOI: 10.6084/m9.figshare.1288863.v2
title: Identification of miRNAs that modulate glucocerebrosidase activity in Gaucher disease cells

description: Gaucher disease is an autosomal recessive disorder caused by deficiency of the enzyme glucocerebrosidase. Although it is a monogenic disease, there is vast phenotypic heterogeneity, even among patients with the same genotype. MicroRNAs (miRNAs) are small non-coding RNAs involved in many biological processes and diseases. To determine whether miRNAs can affect glucocerebrosidase activity, we performed a screen of 875 different miRNA mimics. The screen was performed using Gaucher fibroblasts, and glucocerebrosidase activity was used as the initial outcome parameter. We found several miRNAs that either up- or down-regulated glucocerebrosidase activity. In follow-up assays, we confirmed that one specific miRNA (miR-127–5p) down-regulated both glucocerebrosidase activity and protein levels by down-regulation of LIMP-2, the receptor involved in proper trafficking of glucocerebrosidase from the endoplasmic reticulum to the lysosome. A conditioned media assay demonstrated that cells treated with this miRNA secreted glucocerebrosidase into the extracellular environment, supporting impaired LIMP-2 function. Two other miRNAs, miR-16–5p and miR-195–5p, were found to up-regulate glucocerebrosidase activity by greater than 40% and to enhance expression and protein levels of the enzyme. In conclusion, we show that miRNAs can alter glucocerebrosidase activity in patient cells, indicating that miRNAs can potentially act as modifiers in Gaucher disease.
DOI: 10.6084/m9.figshare.1289845
title: Frequent amplification of <i>PTP1B</i> is associated with poor survival of gastric cancer patients

description: The protein tyrosine phosphatase 1B (<i>PTP1B</i>), a non-transmembrane protein tyrosine phosphatase, has been implicated in gastric pathogenesis. Several lines of recent evidences have shown that <i>PTP1B</i> is highly amplified in breast and prostate cancers. The aim of this study was to investigate <i>PTP1B</i> amplification in gastric cancer and its association with poor prognosis of gastric cancer patients, and further determine the role of <i>PTP1B</i> in gastric tumorigenesis. Our data demonstrated that <i>PTP1B</i> was significantly up-regulated in gastric cancer tissues as compared with matched normal gastric tissues by using quantitative RT-PCR (qRT-PCR) assay. In addition, copy number analysis showed that <i>PTP1B</i> was amplified in 68/131 (51.9%) gastric cancer cases, whereas no amplification was found in the control subjects. Notably, <i>PTP1B</i> amplification was positively associated with its protein expression, and was significantly related to poor survival of gastric cancer patients. Knocking down <i>PTP1B</i> expression in gastric cancer cells significantly inhibited cell proliferation, colony formation, migration and invasion, and induced cell cycle arrested and apoptosis. Mechanically, <i>PTP1B</i> promotes gastric cancer cell proliferation, survival and invasiveness through modulating Src-related signaling pathways, such as Src/Ras/MAPK and Src/phosphatidylinositol-3-kinase (PI3K)/Akt pathways. Collectively, our data demonstrated frequent overexpression and amplification <i>PTP1B</i> in gastric cancer, and further determined the oncogenic role of <i>PTP1B</i> in gastric carcinogenesis. Importantly, <i>PTP1B</i> amplification predicts poor survival of gastric cancer patients.
DOI: 10.6084/m9.figshare.1289845.v1
title: Frequent amplification of <i>PTP1B</i> is associated with poor survival of gastric cancer patients

description: The protein tyrosine phosphatase 1B (<i>PTP1B</i>), a non-transmembrane protein tyrosine phosphatase, has been implicated in gastric pathogenesis. Several lines of recent evidences have shown that <i>PTP1B</i> is highly amplified in breast and prostate cancers. The aim of this study was to investigate <i>PTP1B</i> amplification in gastric cancer and its association with poor prognosis of gastric cancer patients, and further determine the role of <i>PTP1B</i> in gastric tumorigenesis. Our data demonstrated that <i>PTP1B</i> was significantly up-regulated in gastric cancer tissues as compared with matched normal gastric tissues by using quantitative RT-PCR (qRT-PCR) assay. In addition, copy number analysis showed that <i>PTP1B</i> was amplified in 68/131 (51.9%) gastric cancer cases, whereas no amplification was found in the control subjects. Notably, <i>PTP1B</i> amplification was positively associated with its protein expression, and was significantly related to poor survival of gastric cancer patients. Knocking down <i>PTP1B</i> expression in gastric cancer cells significantly inhibited cell proliferation, colony formation, migration and invasion, and induced cell cycle arrested and apoptosis. Mechanically, <i>PTP1B</i> promotes gastric cancer cell proliferation, survival and invasiveness through modulating Src-related signaling pathways, such as Src/Ras/MAPK and Src/phosphatidylinositol-3-kinase (PI3K)/Akt pathways. Collectively, our data demonstrated frequent overexpression and amplification <i>PTP1B</i> in gastric cancer, and further determined the oncogenic role of <i>PTP1B</i> in gastric carcinogenesis. Importantly, <i>PTP1B</i> amplification predicts poor survival of gastric cancer patients.
DOI: 10.6084/m9.figshare.1289845.v2
title: Frequent amplification of <i>PTP1B</i> is associated with poor survival of gastric cancer patients

description: The protein tyrosine phosphatase 1B (<i>PTP1B</i>), a non-transmembrane protein tyrosine phosphatase, has been implicated in gastric pathogenesis. Several lines of recent evidences have shown that <i>PTP1B</i> is highly amplified in breast and prostate cancers. The aim of this study was to investigate <i>PTP1B</i> amplification in gastric cancer and its association with poor prognosis of gastric cancer patients, and further determine the role of <i>PTP1B</i> in gastric tumorigenesis. Our data demonstrated that <i>PTP1B</i> was significantly up-regulated in gastric cancer tissues as compared with matched normal gastric tissues by using quantitative RT-PCR (qRT-PCR) assay. In addition, copy number analysis showed that <i>PTP1B</i> was amplified in 68/131 (51.9%) gastric cancer cases, whereas no amplification was found in the control subjects. Notably, <i>PTP1B</i> amplification was positively associated with its protein expression, and was significantly related to poor survival of gastric cancer patients. Knocking down <i>PTP1B</i> expression in gastric cancer cells significantly inhibited cell proliferation, colony formation, migration and invasion, and induced cell cycle arrested and apoptosis. Mechanically, <i>PTP1B</i> promotes gastric cancer cell proliferation, survival and invasiveness through modulating Src-related signaling pathways, such as Src/Ras/MAPK and Src/phosphatidylinositol-3-kinase (PI3K)/Akt pathways. Collectively, our data demonstrated frequent overexpression and amplification <i>PTP1B</i> in gastric cancer, and further determined the oncogenic role of <i>PTP1B</i> in gastric carcinogenesis. Importantly, <i>PTP1B</i> amplification predicts poor survival of gastric cancer patients.