cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.5568409.v1
title: DNA methylation and obesity traits: An epigenome-wide association study. The REGICOR study

description: Obesity is associated with increased risk of several diseases and has become epidemic. Obesity is highly heritable but the genetic variants identified by genome-wide association studies explain only limited variability. Epigenetics could contribute to explain the missing variability. The study aim was to discover differential methylation patterns related to obesity. We designed an epigenome-wide association study with a discovery phase in a subsample of 641 REGICOR study participants, validated by analysis of 2,515 participants in the Framingham Offspring Study. Blood DNA methylation was assessed using Illumina HumanMethylation450 BeadChip. Next, we meta-analyzed the data using the fixed effects method and performed a functional and pathway analysis using the Ingenuity Pathway Analysis software. We were able to validate 94 CpGs associated with body mass index (BMI) and 49 CpGs associated with waist circumference, located in 95 loci. In addition, we newly discovered 70 CpGs associated with BMI and 33 CpGs related to waist circumference. These CpGs explained 25.94% and 29.22% of the variability of BMI and waist circumference, respectively, in the REGICOR sample. We also evaluated 65 of the 95 validated loci in the GIANT genome-wide association data; 10 of them had Tag SNPs associated with BMI. The top-ranked diseases and functions identified in the functional and pathway analysis were neurologic, psychological, endocrine, and metabolic.
DOI: 10.6084/m9.figshare.5568412.v1
title: Short versus long double-stranded RNA activation of a post-transcriptional gene knockdown pathway

description: RNA interference (RNAi) utilizes a conserved cellular autoimmune defense mechanism involving the internalization of dsRNA into cells and the activation of a set of RNAi related genes. Using RNAi, complete sex reversal is achievable in males of the prawn <i>Macrobrachium rosenbergii</i> by knocking down the transcript level of an insulin-like androgenic gland hormone (<i>Mr-IAG</i>) through injections of dsRNA of the entire <i>Mr-IAG</i> ORF sequence (ds<i>Mr-IAG</i> – 518bp). Interestingly, <i>in-vivo</i> knockdown success and ds<i>Mr-IAG</i> lengths seemed to correlate, with long dsRNA being the most effective and short dsRNA fragments showing no effect. However, little is known about the RNAi machinery in <i>M. rosenbergii</i>. We discovered the <i>Mr-Dicer</i> and <i>Mr-Argonaute</i> gene families, associated with the major knockdown pathways, in our <i>M. rosenbergii</i> transcriptomic library. In response to ds<i>Mr-IAG</i> administration, only post-transcriptional pathway-related gene transcript levels were upregulated. In addition, a passive dsRNA channel (a <i>SID1</i> gene ortholog) that allows external dsRNA to enter cells was found. Its function was validated by observing <i>Mr-SID1</i> specific upregulation dependent on dsRNA lengths, while attempted loss-of-function experiments were lethal. Our results, which suggest differential systemic responses to dsRNA lengths, provide evidence that the above RNAi-based manipulation occurs via the post-transcriptional pathway. The temporal nature of the latter pathway supports the safety of using such RNAi-based biotechnologies in aquaculture and environmental applications. Unlike reports of RNAi driven by the administration of small dsRNA fragments <i>in-vitro</i>, the case presented here demonstrates length dependency <i>in-vivo</i>, suggesting further complexity in the context of the entire organism.
DOI: 10.6084/m9.figshare.5568397
title: A comparative study of sequence- and structure-based features of small RNAs and other RNAs of bacteria

description: Small RNAs (sRNAs) in bacteria have emerged as key players in transcriptional and post-transcriptional regulation of gene expression. Here, we present a statistical analysis of different sequence- and structure-related features of bacterial sRNAs to identify the descriptors that could discriminate sRNAs from other bacterial RNAs. We investigated a comprehensive and heterogeneous collection of 816 sRNAs, identified by northern blotting across 33 bacterial species and compared their various features with other classes of bacterial RNAs, such as tRNAs, rRNAs and mRNAs. We observed that sRNAs differed significantly from the rest with respect to G+C composition, normalized minimum free energy of folding, motif frequency and several RNA-folding parameters like base-pairing propensity, Shannon entropy and base-pair distance. Based on the selected features, we developed a predictive model using Random Forests (RF) method to classify the above four classes of RNAs. Our model displayed an overall predictive accuracy of 89.5%. These findings would help to differentiate bacterial sRNAs from other RNAs and further promote prediction of novel sRNAs in different bacterial species.
DOI: 10.6084/m9.figshare.5568397.v1
title: A comparative study of sequence- and structure-based features of small RNAs and other RNAs of bacteria

description: Small RNAs (sRNAs) in bacteria have emerged as key players in transcriptional and post-transcriptional regulation of gene expression. Here, we present a statistical analysis of different sequence- and structure-related features of bacterial sRNAs to identify the descriptors that could discriminate sRNAs from other bacterial RNAs. We investigated a comprehensive and heterogeneous collection of 816 sRNAs, identified by northern blotting across 33 bacterial species and compared their various features with other classes of bacterial RNAs, such as tRNAs, rRNAs and mRNAs. We observed that sRNAs differed significantly from the rest with respect to G+C composition, normalized minimum free energy of folding, motif frequency and several RNA-folding parameters like base-pairing propensity, Shannon entropy and base-pair distance. Based on the selected features, we developed a predictive model using Random Forests (RF) method to classify the above four classes of RNAs. Our model displayed an overall predictive accuracy of 89.5%. These findings would help to differentiate bacterial sRNAs from other RNAs and further promote prediction of novel sRNAs in different bacterial species.
DOI: 10.6084/m9.figshare.5568400
title: <i>PAX5</i> gene as a novel methylation marker that predicts both clinical outcome and cisplatin sensitivity in esophageal squamous cell carcinoma

description: Therapeutic strategies for esophageal cancer largely depend on histopathological assessment. To select appropriate treatments of individual patients, we examined the background molecular characteristics of tumor malignancy and sensitivity to multidisciplinary therapy. Seventy-eight surgically-resected esophageal squamous cell carcinoma (ESCC) cases during 2001–2013 were examined. <i>PAX5</i>, a novel gene methylation marker in ESCC, was evaluated in the specimens, as methylation of this gene was identified as an extremely tumor-specific event in squamous cell carcinogenesis of head and neck. <i>PAX5</i> methylation status was evaluated by quantitative MSP (QMSP) assays. Mean QMSP value was 15.7 (0–136.3) in ESCCs and 0.3 (0–8.6) in adjacent normal tissues (<i>P</i> &lt; 0.001). The 78 cases were divided into high QMSP value (high QMSP, n = 26) and low QMSP value (low QMSP, n = 52). High QMSP cases were significantly associated with downregulated <i>PAX5</i> expression (<i>P</i> = 0.040), and showed significantly poor recurrence-free survival [Hazard Ratio (HR) = 2.84; <i>P</i> = 0.005; 95% Confidence Interval (CI): 1.39–5.81] and overall survival (HR = 3.23; <i>P</i> = 0.002; 95%CI: 1.52–7.01) in multivariable analyses with histopathological factors. PAX5-knockdown cells exhibited significantly increased cell proliferation and cisplatin resistance. <i>PAX5</i> gene methylation can predict poor survival outcomes and cisplatin sensitivity in ESCCs and could be a useful diagnostic tool for cancer therapy selection.
DOI: 10.6084/m9.figshare.5568400.v2
title: <i>PAX5</i> gene as a novel methylation marker that predicts both clinical outcome and cisplatin sensitivity in esophageal squamous cell carcinoma

description: Therapeutic strategies for esophageal cancer largely depend on histopathological assessment. To select appropriate treatments of individual patients, we examined the background molecular characteristics of tumor malignancy and sensitivity to multidisciplinary therapy. Seventy-eight surgically-resected esophageal squamous cell carcinoma (ESCC) cases during 2001–2013 were examined. <i>PAX5</i>, a novel gene methylation marker in ESCC, was evaluated in the specimens, as methylation of this gene was identified as an extremely tumor-specific event in squamous cell carcinogenesis of head and neck. <i>PAX5</i> methylation status was evaluated by quantitative MSP (QMSP) assays. Mean QMSP value was 15.7 (0–136.3) in ESCCs and 0.3 (0–8.6) in adjacent normal tissues (<i>P</i> &lt; 0.001). The 78 cases were divided into high QMSP value (high QMSP, n = 26) and low QMSP value (low QMSP, n = 52). High QMSP cases were significantly associated with downregulated <i>PAX5</i> expression (<i>P</i> = 0.040), and showed significantly poor recurrence-free survival [Hazard Ratio (HR) = 2.84; <i>P</i> = 0.005; 95% Confidence Interval (CI): 1.39–5.81] and overall survival (HR = 3.23; <i>P</i> = 0.002; 95%CI: 1.52–7.01) in multivariable analyses with histopathological factors. PAX5-knockdown cells exhibited significantly increased cell proliferation and cisplatin resistance. <i>PAX5</i> gene methylation can predict poor survival outcomes and cisplatin sensitivity in ESCCs and could be a useful diagnostic tool for cancer therapy selection.
DOI: 10.6084/m9.figshare.5568382
title: Calpain2 mediates Rab5-driven focal adhesion disassembly and cell migration

description: The early endosome protein Rab5 was recently shown to promote cell migration by enhancing focal adhesion disassembly through mechanisms that remain elusive. Focal adhesion disassembly is associated to proteolysis of talin, in a process that requires calpain2. Since calpain2 has been found at vesicles and endosomal compartments, we hypothesized that Rab5 stimulates calpain2 activity, leading to enhanced focal adhesion disassembly in migrating cells. We observed that calpain2 co-localizes with EEA1-positive early endosomes and co-immunoprecipitates with EEA1 and Rab5 in A549 lung carcinoma cells undergoing spreading, whereas Rab5 knock-down decreased the accumulation of calpain2 at early endosomal-enriched fractions. In addition, Rab5 silencing decreased calpain2 activity, as shown by cleavage of the fluorogenic substrate tBOC-LM-CMAC and the endogenous substrate talin. Accordingly, Rab5 promoted focal adhesion disassembly in a calpain2-dependent manner, as expression of GFP-Rab5 accelerated focal adhesion disassembly in nocodazole-synchronized cells, whereas pharmacological inhibition of calpain2 with N-acetyl-Leu-Leu-Met prevented both focal adhesion disassembly and cell migration induced by Rab5. In summary, these data uncover Rab5 as a novel regulator of calpain2 activity and focal adhesion proteolysis leading to cell migration.
DOI: 10.6084/m9.figshare.5568388
title: Lowly methylated region analysis identifies EBF1 as a potential epigenetic modifier in breast cancer

description: Breast cancer (BC) encompasses heterogeneous pathologies with different subtypes exhibiting distinct molecular changes, including those related to DNA methylation. However, the role of these changes in mediating BC heterogeneity is poorly understood. Lowly methylated regions (LMRs), non-CpG island loci that usually contain transcription factor (TF) binding sites, have been suggested to act as regulatory elements that define cellular identity. In this study, we aimed to identify the key subtype-specific TFs that may lead to LMR generation and shape the BC methylome and transcription program. We initially used whole-genome bisulfite sequencing (WGBS) data available at The Cancer Genome Atlas (TCGA) portal to identify subtype-specific LMRs. Differentially methylated regions (DMRs) within the BC PAM50 subtype-specific LMRs were selected by comparing tumors and normal tissues in a larger TCGA cohort assessed by HumanMethylation450 BeadChip (450K) arrays and TF enrichment analyses were performed. To assess the impact of LMRs on gene expression, TCGA RNA sequencing data were downloaded and Pearson correlations between methylation levels of loci presenting subtype-specific TF motifs and expression of the nearest genes were calculated. WGBS methylome data revealed a large number of LMRs for each of the BC subtypes. Analysis of these LMRs in the 450K datasets available for a larger sample set identified 7,765, 5,657, and 19 differentially methylated positions (DMPs) between normal adjacent tissues and tumor tissues from basal, luminal, and HER2-enriched subtypes, respectively. Unsupervised clustering showed that the discriminatory power of the top DMPs was remarkably strong for basal BC. Interestingly, in this particular subtype, we found 4,409 differentially hypomethylated positions grouped into 1,185 DMRs with a strong enrichment for the early B-cell factor 1 (EBF1) motifs. The methylation levels of the DMRs containing EBF1 motifs showed a strong negative correlation with the expression of 719 nearby genes, including <i>BTS2</i> and <i>CD74</i>, two oncogenes known to be specific for basal BC subtype and for poor outcome. This study identifies LMRs specific to the three main BC subtypes and reveals EBF1 as a potentially important regulator of BC subtype-specific methylation and gene expression program.
DOI: 10.6084/m9.figshare.5568382.v1
title: Calpain2 mediates Rab5-driven focal adhesion disassembly and cell migration

description: The early endosome protein Rab5 was recently shown to promote cell migration by enhancing focal adhesion disassembly through mechanisms that remain elusive. Focal adhesion disassembly is associated to proteolysis of talin, in a process that requires calpain2. Since calpain2 has been found at vesicles and endosomal compartments, we hypothesized that Rab5 stimulates calpain2 activity, leading to enhanced focal adhesion disassembly in migrating cells. We observed that calpain2 co-localizes with EEA1-positive early endosomes and co-immunoprecipitates with EEA1 and Rab5 in A549 lung carcinoma cells undergoing spreading, whereas Rab5 knock-down decreased the accumulation of calpain2 at early endosomal-enriched fractions. In addition, Rab5 silencing decreased calpain2 activity, as shown by cleavage of the fluorogenic substrate tBOC-LM-CMAC and the endogenous substrate talin. Accordingly, Rab5 promoted focal adhesion disassembly in a calpain2-dependent manner, as expression of GFP-Rab5 accelerated focal adhesion disassembly in nocodazole-synchronized cells, whereas pharmacological inhibition of calpain2 with N-acetyl-Leu-Leu-Met prevented both focal adhesion disassembly and cell migration induced by Rab5. In summary, these data uncover Rab5 as a novel regulator of calpain2 activity and focal adhesion proteolysis leading to cell migration.
DOI: 10.6084/m9.figshare.5568388.v1
title: Lowly methylated region analysis identifies EBF1 as a potential epigenetic modifier in breast cancer

description: Breast cancer (BC) encompasses heterogeneous pathologies with different subtypes exhibiting distinct molecular changes, including those related to DNA methylation. However, the role of these changes in mediating BC heterogeneity is poorly understood. Lowly methylated regions (LMRs), non-CpG island loci that usually contain transcription factor (TF) binding sites, have been suggested to act as regulatory elements that define cellular identity. In this study, we aimed to identify the key subtype-specific TFs that may lead to LMR generation and shape the BC methylome and transcription program. We initially used whole-genome bisulfite sequencing (WGBS) data available at The Cancer Genome Atlas (TCGA) portal to identify subtype-specific LMRs. Differentially methylated regions (DMRs) within the BC PAM50 subtype-specific LMRs were selected by comparing tumors and normal tissues in a larger TCGA cohort assessed by HumanMethylation450 BeadChip (450K) arrays and TF enrichment analyses were performed. To assess the impact of LMRs on gene expression, TCGA RNA sequencing data were downloaded and Pearson correlations between methylation levels of loci presenting subtype-specific TF motifs and expression of the nearest genes were calculated. WGBS methylome data revealed a large number of LMRs for each of the BC subtypes. Analysis of these LMRs in the 450K datasets available for a larger sample set identified 7,765, 5,657, and 19 differentially methylated positions (DMPs) between normal adjacent tissues and tumor tissues from basal, luminal, and HER2-enriched subtypes, respectively. Unsupervised clustering showed that the discriminatory power of the top DMPs was remarkably strong for basal BC. Interestingly, in this particular subtype, we found 4,409 differentially hypomethylated positions grouped into 1,185 DMRs with a strong enrichment for the early B-cell factor 1 (EBF1) motifs. The methylation levels of the DMRs containing EBF1 motifs showed a strong negative correlation with the expression of 719 nearby genes, including <i>BTS2</i> and <i>CD74</i>, two oncogenes known to be specific for basal BC subtype and for poor outcome. This study identifies LMRs specific to the three main BC subtypes and reveals EBF1 as a potentially important regulator of BC subtype-specific methylation and gene expression program.
DOI: 10.6084/m9.figshare.5568271
title: Data from: Age-related changes in oscillatory power affect motor action

description: This repository contains the dataset from the publication:<br><br>L. Liu, N. Rosjat, S. Popovych, B. A. Wang, A. Yeldesbay, T. I. Toth, S. Viswanathan, C. B. Grefkes, G. R. Fink, S.Daun. <br>Age-related changes in oscillatory power affect motor action. <i>PLOS ONE</i>.<br><br>The detailed description is given in README file. <br>For details regarding data acquisition, experimental setup, and preprocessing please see materials and methods section of the article. For further questions please contact Silvia Daun: s.daun@fz-juelich.de
DOI: 10.6084/m9.figshare.5568226
title: JHI_5035

description: JHI_5035 E. coli compost isolate
DOI: 10.6084/m9.figshare.5568271.v1
title: Data from: Age-related changes in oscillatory power affect motor action

description: This repository contains the dataset from the publication:<br><br>L. Liu, N. Rosjat, S. Popovych, B. A. Wang, A. Yeldesbay, T. I. Toth, S. Viswanathan, C. B. Grefkes, G. R. Fink, S.Daun. <br>Age-related changes in oscillatory power affect motor action. <i>PLOS ONE</i>.<br><br>The detailed description is given in README file. <br>For details regarding data acquisition, experimental setup, and preprocessing please see materials and methods section of the article. For further questions please contact Silvia Daun: s.daun@fz-juelich.de
DOI: 10.6084/m9.figshare.5568226.v1
title: JHI_5035

description: JHI_5035 E. coli compost isolate
DOI: 10.6084/m9.figshare.5568232
title: On the tolerance of charophytes to high-nitrate concentrations

description: Currently a debate exists about whether the reduced growth of macrophytes with increased nitrogen loading in shallow ecosystems is determined by ecological or physiological factors. To discover whether nitrate in the water is detrimental <i>per se</i> to charophytes, we subjected <i>Chara hispida</i> and <i>Chara vulgaris</i> specimens<i>,</i> collected from two habitats greatly differing in nitrate concentrations (1.5 and 10 mg NO<sub>3</sub>-N/L, annual means), to a wide nitrate range (0.5–50 mg NO<sub>3</sub>-N/L) in two experiments (with free-floating specimens using nitrate as the sole N source, and with planted specimens, with other N sources in sediment). Charophytes grew both unplanted and planted in all treatments, and growth reductions occurred at the highest concentration in all cases. Some charophyte responses when faced with nitrate increases were different depending on (i) the species and (ii) population origin. Under the most realistic situation, the growth of both planted <i>C. vulgaris</i> populations was higher than that of <i>C. hispida</i> populations. <i>C. vulgaris</i> specimens from the nitrate-rich waterbody adapted best to the highest nitrate concentrations when they grew floating. Despite charophytes being vital and growing under high-nitrate concentrations in short-term laboratory experiments, such a situation in the environment may eventually not be sustainable, since ecological factors act in the field.
DOI: 10.6084/m9.figshare.5568223
title: JHI_5034

description: JHI_5034 E. coli compost isolate
DOI: 10.6084/m9.figshare.5568232.v1
title: On the tolerance of charophytes to high-nitrate concentrations

description: Currently a debate exists about whether the reduced growth of macrophytes with increased nitrogen loading in shallow ecosystems is determined by ecological or physiological factors. To discover whether nitrate in the water is detrimental <i>per se</i> to charophytes, we subjected <i>Chara hispida</i> and <i>Chara vulgaris</i> specimens<i>,</i> collected from two habitats greatly differing in nitrate concentrations (1.5 and 10 mg NO<sub>3</sub>-N/L, annual means), to a wide nitrate range (0.5–50 mg NO<sub>3</sub>-N/L) in two experiments (with free-floating specimens using nitrate as the sole N source, and with planted specimens, with other N sources in sediment). Charophytes grew both unplanted and planted in all treatments, and growth reductions occurred at the highest concentration in all cases. Some charophyte responses when faced with nitrate increases were different depending on (i) the species and (ii) population origin. Under the most realistic situation, the growth of both planted <i>C. vulgaris</i> populations was higher than that of <i>C. hispida</i> populations. <i>C. vulgaris</i> specimens from the nitrate-rich waterbody adapted best to the highest nitrate concentrations when they grew floating. Despite charophytes being vital and growing under high-nitrate concentrations in short-term laboratory experiments, such a situation in the environment may eventually not be sustainable, since ecological factors act in the field.
DOI: 10.6084/m9.figshare.5568211
title: JHI_5002

description: JHI_5002 E. coli bovine slurry isolate
DOI: 10.6084/m9.figshare.5568163
title: 2017-11-3-Electronic supplementary information.pdf

description: Interaction between pesticide hexazinone (HEX) and five imidazolium-based ionic liquids (ILs) in different exposure time were analyzed by the using combination index (CI).According to CI, all the five mixture systems exhibit time-dependent synergism or antagonism growing clearer or weaker with exposure time lengthening. And antagonism only shows in one mixture system and synergism in the other four mixture system.
DOI: 10.6084/m9.figshare.5568223.v1
title: JHI_5034

description: JHI_5034 E. coli compost isolate
DOI: 10.6084/m9.figshare.5568163.v1
title: 2017-11-3-Electronic supplementary information.pdf

description: Interaction between pesticide hexazinone (HEX) and five imidazolium-based ionic liquids (ILs) in different exposure time were analyzed by the using combination index (CI).According to CI, all the five mixture systems exhibit time-dependent synergism or antagonism growing clearer or weaker with exposure time lengthening. And antagonism only shows in one mixture system and synergism in the other four mixture system.
DOI: 10.6084/m9.figshare.5568211.v1
title: JHI_5002

description: JHI_5002 E. coli bovine slurry isolate