cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.1512834.v215
title: Localized Protein Quantification of Blood Brain Barrier Vasculature in Brightfield IHC Images

description: In this paper, we present an objective method for locally quantifying proteins in blood brain barrier (BBB) vasculature using standard immunohistochemistry (IHC) techniques and bright-field microscopy. Images from the hippocampal region at the BBB are acquired using bright-field microscopy and subjected to our immunohistochemistry quantification (IQ) algorithm which is designed to automatically identify and segment microvessels containing the protein glucose transporter 1 (GLUT1). Gabor filtering and k-means clustering are employed to isolate potential vascular structures within cryopsectioned slabs of the hippocampus, which are subsequently subjected to feature extraction followed by classification via decision forest. The false positive rate (FPR) of microvessel classification is characterized using synthetic and non-synthetic IHC image data for image entropies ranging between 3 and 8 bits. The average FPR for synthetic and non-synthetic IHC image data was found to be 5.48% and 5.04%, respectively.
DOI: 10.6084/m9.figshare.1501123.v1
title: Long non-coding RNA Linc00152 is involved in cell cycle arrest, apoptosis, epithelial to mesenchymal transition, cell migration and invasion in gastric cancer

description: Gastric cancer remains a serious threat to public health with high incidence and mortality worldwide. Accumulating evidence demonstrates that long non-coding RNAs (lncRNAs) play important roles in regulating gene expression and are involved in various pathological processes, including gastric cancer. To investigate the possible role of dysregulated lncRNAs in gastric cancer development, we performed lncRNA microarray and identified 3141 significantly differentially expressed lncRNAs in gastric cancer tissues. Next, some of deregulated lncRNAs were validated among about 60 paired gastric cancer specimens such as Linc00261, DKFZP434K028, RPL34-AS1, H19, HOTAIR and Linc00152. Our results found that the decline of DKFZP434K028 and RPL34-AS1, and the increased expression of Linc00152 positively correlated with larger tumor size. The high expression levels of HOTAIR were associated with lymphatic metastasis and poor differentiation. Since the biological roles of Linc00152 are largely unknown in gastric cancer pathogenesis, we assessed its functions by silencing its up-regulation in gastric cancer cells. We found that Linc00152 knockdown could inhibit cell proliferation and colony formation, promote cell cycle arrest at G1 phase, trigger late apoptosis, reduce the epithelial to mesenchymal transition (EMT) program, and suppress cell migration and invasion. Taken together, we delineate the gastric cancer lncRNA signature and demonstrate the oncogenic functions of Linc00152. These findings may have implications for developing lncRNA-based biomarkers for diagnosis and therapeutics for gastric cancer.
DOI: 10.6084/m9.figshare.1501126
title: Heterotrimeric G protein subunits differentially respond to endoplasmic reticulum stress in Arabidopsis

description: Canonical heterotrimeric G proteins in eukaryotes are major components that localize at plasma membrane and transmit extracellular stimuli into the cell. Genome of a seed plant <i>Arabidopsis thaliana</i> encodes at least one Gα (<i>GPA1</i>), one Gβ (<i>AGB1</i>), and 3 Gγ (<i>AGG1, AGG2</i> and <i>AGG3</i>) subunits. The loss-of-function mutations of G protein subunit(s) cause multiple defects in development as well as biotic and abiotic stress responses. However, it remains elusive how these subunits differentially express these defects. Here, we report that Arabidopsis heterotrimeric G protein subunits differentially respond to the endoplasmic reticulum (ER) stress. An isolated homozygous mutant of <i>AGB1, agb1-3</i>, was more sensitive to the tunicamycin-induced ER stress compared to the wild type and the other loss-of-function mutants of G protein subunits. Moreover, ER stress responsive genes were highly expressed in the <i>agb1-3</i> plant. Our results indicate that <i>AGB1</i> positively contributes to ER stress tolerance in Arabidopsis.
DOI: 10.6084/m9.figshare.1501126.v1
title: Heterotrimeric G protein subunits differentially respond to endoplasmic reticulum stress in Arabidopsis

description: Canonical heterotrimeric G proteins in eukaryotes are major components that localize at plasma membrane and transmit extracellular stimuli into the cell. Genome of a seed plant <i>Arabidopsis thaliana</i> encodes at least one Gα (<i>GPA1</i>), one Gβ (<i>AGB1</i>) and three Gγ (<i>AGG1, AGG2</i> and <i>AGG3</i>) subunits. The loss-of-function mutations of G protein subunit(s) cause multiple defects in development as well as biotic and abiotic stress responses. However, it remains elusive how these subunits differentially express these defects. Here, we report that Arabidopsis heterotrimeric G protein subunits differentially respond to the endoplasmic reticulum (ER) stress. An isolated homozygous mutant of <i>AGB1, agb1-3</i>, was more sensitive to the tunicamycin-induced ER stress compared to the wild type and the other loss-of-function mutants of G protein subunits. Moreover, ER stress responsive genes were highly expressed in the <i>agb1-3</i> plant. Our results indicate that <i>AGB1</i> positively contribute to ER stress tolerance in Arabidopsis.
DOI: 10.6084/m9.figshare.1501123.v3
title: Long non-coding RNA Linc00152 is involved in cell cycle arrest, apoptosis, epithelial to mesenchymal transition, cell migration and invasion in gastric cancer

description: Gastric cancer remains a serious threat to public health with high incidence and mortality worldwide. Accumulating evidence demonstrates that long non-coding RNAs (lncRNAs) play important roles in regulating gene expression and are involved in various pathological processes, including gastric cancer. To investigate the possible role of dysregulated lncRNAs in gastric cancer development, we performed lncRNA microarray and identified 3141 significantly differentially expressed lncRNAs in gastric cancer tissues. Next, some of deregulated lncRNAs were validated among about 60 paired gastric cancer specimens such as Linc00261, DKFZP434K028, RPL34-AS1, H19, HOTAIR and Linc00152. Our results found that the decline of DKFZP434K028 and RPL34-AS1, and the increased expression of Linc00152 positively correlated with larger tumor size. The high expression levels of HOTAIR were associated with lymphatic metastasis and poor differentiation. Since the biological roles of Linc00152 are largely unknown in gastric cancer pathogenesis, we assessed its functions by silencing its up-regulation in gastric cancer cells. We found that Linc00152 knockdown could inhibit cell proliferation and colony formation, promote cell cycle arrest at G1 phase, trigger late apoptosis, reduce the epithelial to mesenchymal transition (EMT) program, and suppress cell migration and invasion. Taken together, we delineate the gastric cancer lncRNA signature and demonstrate the oncogenic functions of Linc00152. These findings may have implications for developing lncRNA-based biomarkers for diagnosis and therapeutics for gastric cancer.
DOI: 10.6084/m9.figshare.1501125.v1
title: Inhibition of polo like kinase 1 in sarcomas induces apoptosis that is dependent on Mcl-1 suppression

description: Sarcomas are rare cancers and the current treatments in inoperable or metastatic disease have not been shown to prolong survival. In order to develop novel targeted therapies, we tested the efficacy of polo-like kinase 1 (PLK-1) inhibitor (TAK-960) in sarcoma.All the sarcoma cell lines were sensitive to TAK-960 with IC50s in the low nanomolar range. We chose MPNST, CHP100 and LS141 for our studies and of which MPNST cells exclusively underwent polyploidy after a delay in mitosis for about 18 hours; CHP100 cells, after a 24h mitotic delay, died of apoptosis; LS141, after a delay in mitosis stayed at 4N with mild apoptosis. Apoptosis induced by TAK-960 in CHP100 was associated with down-regulation of Mcl-1 and the effect was recapitulated by down-regulating PLK1 by siRNA, confirming that the effect of TAK-960 on Mcl-1 expression is target specific. With suppression of Mcl-1 by siRNA, TAK-960 induced apoptosis in MPNST cells as well. These effects were confirmed <i>in vivo</i>, such that TAK-960 more effectively inhibited CHP100 than MPNST xenografts.In the setting of PLK-1 inhibition, Mcl-1 down regulation is shown to be an important determinant of apoptosis. Collectively, the net effect of this is to drive cells to apoptosis, resulting in a greater anti-tumor effect <i>in vivo</i>. Therefore, targeting PLK-1 should have a greater impact in treating sarcomas provided there is concomitant suppression of Mcl-1. These results further indicate that Mcl-1 could be an important biomarker to predict sensitivity to the induction of apoptosis by PLK-1 targeted therapy in sarcoma.
DOI: 10.6084/m9.figshare.1501126.v3
title: Heterotrimeric G protein subunits differentially respond to endoplasmic reticulum stress in Arabidopsis

description: Canonical heterotrimeric G proteins in eukaryotes are major components that localize at plasma membrane and transmit extracellular stimuli into the cell. Genome of a seed plant <i>Arabidopsis thaliana</i> encodes at least one Gα (<i>GPA1</i>), one Gβ (<i>AGB1</i>), and 3 Gγ (<i>AGG1, AGG2</i> and <i>AGG3</i>) subunits. The loss-of-function mutations of G protein subunit(s) cause multiple defects in development as well as biotic and abiotic stress responses. However, it remains elusive how these subunits differentially express these defects. Here, we report that Arabidopsis heterotrimeric G protein subunits differentially respond to the endoplasmic reticulum (ER) stress. An isolated homozygous mutant of <i>AGB1, agb1-3</i>, was more sensitive to the tunicamycin-induced ER stress compared to the wild type and the other loss-of-function mutants of G protein subunits. Moreover, ER stress responsive genes were highly expressed in the <i>agb1-3</i> plant. Our results indicate that <i>AGB1</i> positively contributes to ER stress tolerance in Arabidopsis.
DOI: 10.6084/m9.figshare.1501123.v2
title: Long non-coding RNA Linc00152 is involved in cell cycle arrest, apoptosis, epithelial to mesenchymal transition, cell migration and invasion in gastric cancer

description: Gastric cancer remains a serious threat to public health with high incidence and mortality worldwide. Accumulating evidence demonstrates that long non-coding RNAs (lncRNAs) play important roles in regulating gene expression and are involved in various pathological processes, including gastric cancer. To investigate the possible role of dysregulated lncRNAs in gastric cancer development, we performed lncRNA microarray and identified 3141 significantly differentially expressed lncRNAs in gastric cancer tissues. Next, some of deregulated lncRNAs were validated among about 60 paired gastric cancer specimens such as Linc00261, DKFZP434K028, RPL34-AS1, H19, HOTAIR and Linc00152. Our results found that the decline of DKFZP434K028 and RPL34-AS1, and the increased expression of Linc00152 positively correlated with larger tumor size. The high expression levels of HOTAIR were associated with lymphatic metastasis and poor differentiation. Since the biological roles of Linc00152 are largely unknown in gastric cancer pathogenesis, we assessed its functions by silencing its up-regulation in gastric cancer cells. We found that Linc00152 knockdown could inhibit cell proliferation and colony formation, promote cell cycle arrest at G1 phase, trigger late apoptosis, reduce the epithelial to mesenchymal transition (EMT) program, and suppress cell migration and invasion. Taken together, we delineate the gastric cancer lncRNA signature and demonstrate the oncogenic functions of Linc00152. These findings may have implications for developing lncRNA-based biomarkers for diagnosis and therapeutics for gastric cancer.
DOI: 10.6084/m9.figshare.1512834.v216
title: Localized Protein Quantification of Blood Brain Barrier Vasculature in Brightfield IHC Images

description: In this paper, we present an objective method for locally quantifying proteins in blood brain barrier (BBB) vasculature using standard immunohistochemistry (IHC) techniques and bright-field microscopy. Images from the hippocampal region at the BBB are acquired using bright-field microscopy and subjected to our immunohistochemistry quantification (IQ) algorithm which is designed to automatically identify and segment microvessels containing the protein glucose transporter 1 (GLUT1). Gabor filtering and k-means clustering are employed to isolate potential vascular structures within cryopsectioned slabs of the hippocampus, which are subsequently subjected to feature extraction followed by classification via decision forest. The false positive rate (FPR) of microvessel classification is characterized using synthetic and non-synthetic IHC image data for image entropies ranging between 3 and 8 bits. The average FPR for synthetic and non-synthetic IHC image data was found to be 5.48% and 5.04%, respectively.
DOI: 10.6084/m9.figshare.1501120
title: Epigenetic landscape correlates with genetic subtype but does not predict outcome in childhood acute lymphoblastic leukemia

description: Although children with acute lymphoblastic leukemia (ALL) generally have a good outcome, some patients do relapse and survival following relapse is poor. Altered DNA methylation is highly prevalent in ALL and raises the possibility that DNA methylation-based biomarkers could predict patient outcome. In this study, genome-wide methylation analysis, using the Illumina Infinium HumanMethylation450 BeadChip platform, was carried out on 52 diagnostic patient samples from 4 genetic subtypes [<i>ETV6-RUNX1</i>, high hyperdiploidy (HeH), <i>TCF3-PBX1</i> and dic(9;20)(p11–13;q11)] in a 1:1 case-control design with patients who went on to relapse (as cases) and patients achieving long-term remission (as controls). Pyrosequencing assays for selected loci were used to confirm the array-generated data. Non-negative matrix factorization consensus clustering readily clustered samples according to genetic subgroups and gene enrichment pathway analysis suggested that this is in part driven by epigenetic disruption of subtype specific signaling pathways. Multiple bioinformatics approaches (including bump hunting and individual locus analysis) were used to identify CpG sites or regions associated with outcome. However, no associations with relapse were identified. Our data revealed that <i>ETV6-RUNX1</i> and dic(9;20) subtypes were mostly associated with hypermethylation; conversely, <i>TCF3-PBX1</i> and HeH were associated with hypomethylation. We observed significant enrichment of the neuroactive ligand-receptor interaction pathway in <i>TCF3-PBX1</i> as well as an enrichment of genes involved in immunity and infection pathways in <i>ETV6-RUNX1</i> subtype. Taken together, our results suggest that altered DNA methylation may have differential impacts in distinct ALL genetic subtypes.
DOI: 10.6084/m9.figshare.1501126.v2
title: Heterotrimeric G protein subunits differentially respond to endoplasmic reticulum stress in Arabidopsis

description: Canonical heterotrimeric G proteins in eukaryotes are major components that localize at plasma membrane and transmit extracellular stimuli into the cell. Genome of a seed plant <i>Arabidopsis thaliana</i> encodes at least one Gα (<i>GPA1</i>), one Gβ (<i>AGB1</i>), and 3 Gγ (<i>AGG1, AGG2</i> and <i>AGG3</i>) subunits. The loss-of-function mutations of G protein subunit(s) cause multiple defects in development as well as biotic and abiotic stress responses. However, it remains elusive how these subunits differentially express these defects. Here, we report that Arabidopsis heterotrimeric G protein subunits differentially respond to the endoplasmic reticulum (ER) stress. An isolated homozygous mutant of <i>AGB1, agb1-3</i>, was more sensitive to the tunicamycin-induced ER stress compared to the wild type and the other loss-of-function mutants of G protein subunits. Moreover, ER stress responsive genes were highly expressed in the <i>agb1-3</i> plant. Our results indicate that <i>AGB1</i> positively contributes to ER stress tolerance in Arabidopsis.
DOI: 10.6084/m9.figshare.1501119
title: DNA methylation mediates the impact of exposure to prenatal maternal stress on BMI and central adiposity in children at age 13½ years: Project Ice Storm

description: Prenatal maternal stress (PNMS) in animals and humans predicts obesity and metabolic dysfunction in the offspring. Epigenetic modification of gene function is considered one possible mechanism by which PNMS results in poor outcomes in offspring. Our goal was to determine the role of maternal objective exposure and subjective distress on child BMI and central adiposity at 13½ years of age, and to test the hypothesis that DNA methylation mediates the effect of PNMS on growth. Mothers were pregnant during the January 1998 Quebec ice storm. We assessed their objective exposure and subjective distress in June 1998. At age 13½ their children were weighed and measured (n = 66); a subsample provided blood samples for epigenetic studies (n = 31). Objective and subjective PNMS correlated with central adiposity (waist-to-height ratio); only objective PNMS predicted body mass index (BMI). Bootstrapping analyses showed that the methylation level of genes from established Type-1 and -2 diabetes mellitus pathways showed significant mediation of the effect of objective PNMS on both central adiposity and BMI. However, the negative mediating effects indicate that, although greater objective PNMS predicts greater BMI and adiposity, this effect is dampened by the effects of objective PNMS on DNA methylation, suggesting a protective role of the selected genes from Type-1 and -2 diabetes mellitus pathways. We provide data supporting that DNA methylation is a potential mechanism involved in the long-term adaptation and programming of the genome in response to early adverse environmental factors.
DOI: 10.6084/m9.figshare.1512834.v217
title: Localized Protein Quantification of Blood Brain Barrier Vasculature in Brightfield IHC Images

description: In this paper, we present an objective method for locally quantifying proteins in blood brain barrier (BBB) vasculature using standard immunohistochemistry (IHC) techniques and bright-field microscopy. Images from the hippocampal region at the BBB are acquired using bright-field microscopy and subjected to our immunohistochemistry quantification (IQ) algorithm which is designed to automatically identify and segment microvessels containing the protein glucose transporter 1 (GLUT1). Gabor filtering and k-means clustering are employed to isolate potential vascular structures within cryopsectioned slabs of the hippocampus, which are subsequently subjected to feature extraction followed by classification via decision forest. The false positive rate (FPR) of microvessel classification is characterized using synthetic and non-synthetic IHC image data for image entropies ranging between 3 and 8 bits. The average FPR for synthetic and non-synthetic IHC image data was found to be 5.48% and 5.04%, respectively.
DOI: 10.6084/m9.figshare.1501120.v2
title: Epigenetic landscape correlates with genetic subtype but does not predict outcome in childhood acute lymphoblastic leukemia

description: Although children with acute lymphoblastic leukemia (ALL) generally have a good outcome, some patients do relapse and survival following relapse is poor. Altered DNA methylation is highly prevalent in ALL and raises the possibility that DNA methylation-based biomarkers could predict patient outcome. In this study, genome-wide methylation analysis, using the Illumina Infinium HumanMethylation450 BeadChip platform, was carried out on 52 diagnostic patient samples from 4 genetic subtypes [<i>ETV6-RUNX1</i>, high hyperdiploidy (HeH), <i>TCF3-PBX1</i> and dic(9;20)(p11–13;q11)] in a 1:1 case-control design with patients who went on to relapse (as cases) and patients achieving long-term remission (as controls). Pyrosequencing assays for selected loci were used to confirm the array-generated data. Non-negative matrix factorization consensus clustering readily clustered samples according to genetic subgroups and gene enrichment pathway analysis suggested that this is in part driven by epigenetic disruption of subtype specific signaling pathways. Multiple bioinformatics approaches (including bump hunting and individual locus analysis) were used to identify CpG sites or regions associated with outcome. However, no associations with relapse were identified. Our data revealed that <i>ETV6-RUNX1</i> and dic(9;20) subtypes were mostly associated with hypermethylation; conversely, <i>TCF3-PBX1</i> and HeH were associated with hypomethylation. We observed significant enrichment of the neuroactive ligand-receptor interaction pathway in <i>TCF3-PBX1</i> as well as an enrichment of genes involved in immunity and infection pathways in <i>ETV6-RUNX1</i> subtype. Taken together, our results suggest that altered DNA methylation may have differential impacts in distinct ALL genetic subtypes.
DOI: 10.6084/m9.figshare.1501119.v2
title: DNA methylation mediates the impact of exposure to prenatal maternal stress on BMI and central adiposity in children at age 13½ years: Project Ice Storm

description: Prenatal maternal stress (PNMS) in animals and humans predicts obesity and metabolic dysfunction in the offspring. Epigenetic modification of gene function is considered one possible mechanism by which PNMS results in poor outcomes in offspring. Our goal was to determine the role of maternal objective exposure and subjective distress on child BMI and central adiposity at 13½ years of age, and to test the hypothesis that DNA methylation mediates the effect of PNMS on growth. Mothers were pregnant during the January 1998 Quebec ice storm. We assessed their objective exposure and subjective distress in June 1998. At age 13½ their children were weighed and measured (n = 66); a subsample provided blood samples for epigenetic studies (n = 31). Objective and subjective PNMS correlated with central adiposity (waist-to-height ratio); only objective PNMS predicted body mass index (BMI). Bootstrapping analyses showed that the methylation level of genes from established Type-1 and -2 diabetes mellitus pathways showed significant mediation of the effect of objective PNMS on both central adiposity and BMI. However, the negative mediating effects indicate that, although greater objective PNMS predicts greater BMI and adiposity, this effect is dampened by the effects of objective PNMS on DNA methylation, suggesting a protective role of the selected genes from Type-1 and -2 diabetes mellitus pathways. We provide data supporting that DNA methylation is a potential mechanism involved in the long-term adaptation and programming of the genome in response to early adverse environmental factors.