cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.1414164.v3
title: Provenance of detrital zircons in the Late Triassic Sichuan foreland basin: constraints on the evolution of the Qinling Orogen and Longmen Shan thrust-fold belt in central China

description: In this article, we present <i>in situ</i> U–Pb and Lu–Hf isotope data for Upper Triassic detritus in the Sichuan region of northwestern South China, which was a foreland basin during the Late Triassic. The aim is to determine the provenance of sediments in the foreland basin and to constrain the evolution of the surrounding mountain belts. U–Pb age data for the Late Triassic detrital zircons generally show populations at 2.4–2.6 Ga, 1.7–1.9 Ga, 710–860 Ma, 410–460 Ma, and 210–300 Ma. By fitting the zircon data into the tectonic, sedimentologic, and palaeographic framework, we propose that the north Yangtze Block and South Qinling–Dabie Orogen were the important source areas of sediments in the northern part of the foreland basin, whereas the Longmen Shan thrust-fold belt was the main source region for detritus in other parts of the foreland basin. The South Qinling–Dabie Orogen could also have served as a physical barrier to block most detritus shed from the southern North China Block into the foreland basin during the sedimentation of the Xujiahe Formation. Our results also reveal that part of the flysch from the eastern margin of the Songpan–Ganzi region had been displaced into the Longmen Shan thrust-fold belt before the deposition of the foreland basin sediments. In addition, the Lu-Hf data indicate that Phanerozoic igneous rocks in central China show insignificant formation of the juvenile crust.
DOI: 10.6084/m9.figshare.1418235
title: Phylogenetic position of Lycodon gongshan Vogel and Luo, 2011, a snake endemic to China (Reptilia: Colubridae)

description: <em>Lycodon gongshan</em> Vogel and Luo, 2011 is a newly described snake species that is endemic to southwestern China. Based on two mtDNA gene fragments and two nuclear genes, a molecular phylogeny for the genus <em>Lycodon</em> was reconstructed and the systematic position of <em>L. gongshan</em> was evaluated. The results revealed that <em>L. gongshan</em> formed a strongly supported monophyletic clade with <em>L. fasciatus</em>, and (<em>L. cavernicolus</em> + <em>L. butleri</em>), although the relationships among them were unresolved. The close genetic relationship between <em>L. gongshan</em> and <em>L. fasciatus</em> is consistent with hypotheses based on morphological data. Additionally two specimens from Guangdong, previously identified as <em>L. fasciatus</em>, showed a sister relationship with <em>L. liuchengchaoiwith</em> low genetic difference, indicating that the two specimens were misidentified, and illustrating that L. liuchengchaoi may have much broader distribution than previous thought.
DOI: 10.6084/m9.figshare.1418235.v1
title: Phylogenetic position of Lycodon gongshan Vogel and Luo, 2011, a snake endemic to China (Reptilia: Colubridae)

description: <em>Lycodon gongshan</em> Vogel and Luo, 2011 is a newly described snake species that is endemic to southwestern China. Based on two mtDNA gene fragments and two nuclear genes, a molecular phylogeny for the genus <em>Lycodon</em> was reconstructed and the systematic position of <em>L. gongshan</em> was evaluated. The results revealed that <em>L. gongshan</em> formed a strongly supported monophyletic clade with <em>L. fasciatus</em>, and (<em>L. cavernicolus</em> + <em>L. butleri</em>), although the relationships among them were unresolved. The close genetic relationship between <em>L. gongshan</em> and <em>L. fasciatus</em> is consistent with hypotheses based on morphological data. Additionally two specimens from Guangdong, previously identified as <em>L. fasciatus</em>, showed a sister relationship with <em>L. liuchengchaoiwith</em> low genetic difference, indicating that the two specimens were misidentified, and illustrating that L. liuchengchaoi may have much broader distribution than previous thought.
DOI: 10.6084/m9.figshare.1418249
title: The GST-BHMT assay reveals a distinct mechanism underlying proteasome inhibition-induced macroautophagy in mammalian cells

description: By monitoring the fragmentation of a GST-BHMT (a protein fusion of glutathionine S-transferase N-terminal to betaine-homocysteine S-methyltransferase) reporter in lysosomes, the GST-BHMT assay has previously been established as an endpoint, cargo-based assay for starvation-induced autophagy that is largely nonselective. Here, we demonstrate that under nutrient-rich conditions, proteasome inhibition by either pharmaceutical or genetic manipulations induces similar autophagy-dependent GST-BHMT processing. However, mechanistically this proteasome inhibition-induced autophagy is different from that induced by starvation as it does not rely on regulation by MTOR (mechanistic target of rapamycin [serine/threonine kinase]) and PRKAA/AMPK (protein kinase, AMP-activated, α catalytic subunit), the upstream central sensors of cellular nutrition and energy status, but requires the presence of the cargo receptors SQSTM1/p62 (sequestosome 1) and NBR1 (neighbor of BRCA1 gene 1) that are normally involved in the selective autophagy pathway. Further, it depends on ER (endoplasmic reticulum) stress signaling, in particular ERN1/IRE1 (endoplasmic reticulum to nucleus signaling 1) and its main downstream effector MAPK8/JNK1 (mitogen-activated protein kinase 8), but not XBP1 (X-box binding protein 1), by regulating the phosphorylation-dependent disassociation of BCL2 (B-cell CLL/lymphoma 2) from BECN1 (Beclin 1, autophagy related). Moreover, the multimerization domain of GST-BHMT is required for its processing in response to proteasome inhibition, in contrast to its dispensable role in starvation-induced processing. Together, these findings support a model in which under nutrient-rich conditions, proteasome inactivation induces autophagy-dependent processing of the GST-BHMT reporter through a distinct mechanism that bears notable similarity with the yeast Cvt (cytoplasm-to-vacuole targeting) pathway, and suggest the GST-BHMT reporter might be employed as a convenient assay to study selective macroautophagy in mammalian cells.
DOI: 10.6084/m9.figshare.1418249.v1
title: The GST-BHMT Assay Reveals A Distinct Mechanism Underlying Proteasome Inhibition-Induced Macroautophagy in Mammalian Cells

description: By monitoring the fragmentation of a GST-BHMT (a protein fusion of glutathionine S-transferase N-terminal to betaine-homocysteine S-methyltransferase) reporter in lysosomes, the GST-BHMT assay has previously been established as an endpoint, cargo-based assay for starvation-induced autophagy that is largely nonselective. Here, we demonstrate that under nutrient-rich conditions, proteasome inhibition by either pharmaceutical or genetic manipulations induces similar autophagy-dependent GST-BHMT processing. However, mechanistically this proteasome inhibition-induced autophagy is different from that induced by starvation as it does not rely on regulation by MTOR (mechanistic target of rapamycin [serine/threonine kinase]) and PRKAA/AMPK (protein kinase, AMP-activated, alpha catalytic subunit), the upstream central sensors of cellular nutrition and energy status, but requires the presence of the cargo receptors SQSTM1/p62 (sequestosome 1) and NBR1 (neighbor of BRCA1 gene 1) that are normally involved in the selective autophagy pathway. Further, it depends on ER (endoplasmic reticulum) stress signaling, in particular ERN1/IRE1 (endoplasmic reticulum to nucleus signaling 1) and its main downstream effector MAPK8/JNK1 (mitogen-activated protein kinase 8), but not XBP1 (X-box binding protein 1), by regulating the phosphorylation-dependent disassociation of BCL2 (B-cell CLL/lymphoma 2) from BECN1 (beclin 1, autophagy related). Moreover, the multimerization domain of GST-BHMT is required for its processing in response to proteasome inhibition, in contrast to its dispensable role in starvation-induced processing. Together, these findings support a model in which under nutrient-rich conditions, proteasome inactivation induces autophagy-dependent processing of the GST-BHMT reporter through a distinct mechanism that bears notable similarity with the yeast Cvt (cytoplasm to vacuole targeting) pathway, and suggest the GST-BHMT reporter might be employed as a convenient assay to study selective macroautophagy in mammalian cells.
DOI: 10.6084/m9.figshare.1418249.v2
title: The GST-BHMT assay reveals a distinct mechanism underlying proteasome inhibition-induced macroautophagy in mammalian cells

description: By monitoring the fragmentation of a GST-BHMT (a protein fusion of glutathionine S-transferase N-terminal to betaine-homocysteine S-methyltransferase) reporter in lysosomes, the GST-BHMT assay has previously been established as an endpoint, cargo-based assay for starvation-induced autophagy that is largely nonselective. Here, we demonstrate that under nutrient-rich conditions, proteasome inhibition by either pharmaceutical or genetic manipulations induces similar autophagy-dependent GST-BHMT processing. However, mechanistically this proteasome inhibition-induced autophagy is different from that induced by starvation as it does not rely on regulation by MTOR (mechanistic target of rapamycin [serine/threonine kinase]) and PRKAA/AMPK (protein kinase, AMP-activated, α catalytic subunit), the upstream central sensors of cellular nutrition and energy status, but requires the presence of the cargo receptors SQSTM1/p62 (sequestosome 1) and NBR1 (neighbor of BRCA1 gene 1) that are normally involved in the selective autophagy pathway. Further, it depends on ER (endoplasmic reticulum) stress signaling, in particular ERN1/IRE1 (endoplasmic reticulum to nucleus signaling 1) and its main downstream effector MAPK8/JNK1 (mitogen-activated protein kinase 8), but not XBP1 (X-box binding protein 1), by regulating the phosphorylation-dependent disassociation of BCL2 (B-cell CLL/lymphoma 2) from BECN1 (Beclin 1, autophagy related). Moreover, the multimerization domain of GST-BHMT is required for its processing in response to proteasome inhibition, in contrast to its dispensable role in starvation-induced processing. Together, these findings support a model in which under nutrient-rich conditions, proteasome inactivation induces autophagy-dependent processing of the GST-BHMT reporter through a distinct mechanism that bears notable similarity with the yeast Cvt (cytoplasm-to-vacuole targeting) pathway, and suggest the GST-BHMT reporter might be employed as a convenient assay to study selective macroautophagy in mammalian cells.
DOI: 10.6084/m9.figshare.1418249.v4
title: The GST-BHMT assay reveals a distinct mechanism underlying proteasome inhibition-induced macroautophagy in mammalian cells

description: By monitoring the fragmentation of a GST-BHMT (a protein fusion of glutathionine S-transferase N-terminal to betaine-homocysteine S-methyltransferase) reporter in lysosomes, the GST-BHMT assay has previously been established as an endpoint, cargo-based assay for starvation-induced autophagy that is largely nonselective. Here, we demonstrate that under nutrient-rich conditions, proteasome inhibition by either pharmaceutical or genetic manipulations induces similar autophagy-dependent GST-BHMT processing. However, mechanistically this proteasome inhibition-induced autophagy is different from that induced by starvation as it does not rely on regulation by MTOR (mechanistic target of rapamycin [serine/threonine kinase]) and PRKAA/AMPK (protein kinase, AMP-activated, α catalytic subunit), the upstream central sensors of cellular nutrition and energy status, but requires the presence of the cargo receptors SQSTM1/p62 (sequestosome 1) and NBR1 (neighbor of BRCA1 gene 1) that are normally involved in the selective autophagy pathway. Further, it depends on ER (endoplasmic reticulum) stress signaling, in particular ERN1/IRE1 (endoplasmic reticulum to nucleus signaling 1) and its main downstream effector MAPK8/JNK1 (mitogen-activated protein kinase 8), but not XBP1 (X-box binding protein 1), by regulating the phosphorylation-dependent disassociation of BCL2 (B-cell CLL/lymphoma 2) from BECN1 (Beclin 1, autophagy related). Moreover, the multimerization domain of GST-BHMT is required for its processing in response to proteasome inhibition, in contrast to its dispensable role in starvation-induced processing. Together, these findings support a model in which under nutrient-rich conditions, proteasome inactivation induces autophagy-dependent processing of the GST-BHMT reporter through a distinct mechanism that bears notable similarity with the yeast Cvt (cytoplasm-to-vacuole targeting) pathway, and suggest the GST-BHMT reporter might be employed as a convenient assay to study selective macroautophagy in mammalian cells.
DOI: 10.6084/m9.figshare.1418249.v3
title: The GST-BHMT assay reveals a distinct mechanism underlying proteasome inhibition-induced macroautophagy in mammalian cells

description: By monitoring the fragmentation of a GST-BHMT (a protein fusion of glutathionine S-transferase N-terminal to betaine-homocysteine S-methyltransferase) reporter in lysosomes, the GST-BHMT assay has previously been established as an endpoint, cargo-based assay for starvation-induced autophagy that is largely nonselective. Here, we demonstrate that under nutrient-rich conditions, proteasome inhibition by either pharmaceutical or genetic manipulations induces similar autophagy-dependent GST-BHMT processing. However, mechanistically this proteasome inhibition-induced autophagy is different from that induced by starvation as it does not rely on regulation by MTOR (mechanistic target of rapamycin [serine/threonine kinase]) and PRKAA/AMPK (protein kinase, AMP-activated, α catalytic subunit), the upstream central sensors of cellular nutrition and energy status, but requires the presence of the cargo receptors SQSTM1/p62 (sequestosome 1) and NBR1 (neighbor of BRCA1 gene 1) that are normally involved in the selective autophagy pathway. Further, it depends on ER (endoplasmic reticulum) stress signaling, in particular ERN1/IRE1 (endoplasmic reticulum to nucleus signaling 1) and its main downstream effector MAPK8/JNK1 (mitogen-activated protein kinase 8), but not XBP1 (X-box binding protein 1), by regulating the phosphorylation-dependent disassociation of BCL2 (B-cell CLL/lymphoma 2) from BECN1 (Beclin 1, autophagy related). Moreover, the multimerization domain of GST-BHMT is required for its processing in response to proteasome inhibition, in contrast to its dispensable role in starvation-induced processing. Together, these findings support a model in which under nutrient-rich conditions, proteasome inactivation induces autophagy-dependent processing of the GST-BHMT reporter through a distinct mechanism that bears notable similarity with the yeast Cvt (cytoplasm-to-vacuole targeting) pathway, and suggest the GST-BHMT reporter might be employed as a convenient assay to study selective macroautophagy in mammalian cells.
DOI: 10.6084/m9.figshare.1418252
title: Epigenetic silencing of neurofilament genes promotes an aggressive phenotype in breast cancer

description: <i>Neurofilament heavy polypeptide</i> (<i>NEFH</i>) has recently been identified as a candidate DNA hypermethylated gene within the functional breast cancer hypermethylome. NEFH exists in a complex with neurofilament medium polypeptide (NEFM) and neurofilament light polypeptide (NEFL) to form neurofilaments, which are structural components of the cytoskeleton in mature neurons. Recent studies reported the deregulation of these proteins in several malignancies, suggesting that neurofilaments may have a role in other cell types as well. Using a comprehensive approach, we studied the epigenetic inactivation of neurofilament genes in breast cancer and the functional significance of this event. We report that DNA methylation-associated silencing of <i>NEFH</i>, <i>NEFL,</i> and <i>NEFM</i> in breast cancer is frequent, cancer-specific, and correlates with clinical features of disease progression. DNA methylation-mediated inactivation of these genes occurs also in multiple other cancer histologies including pancreas, gastric, and colon. Restoration of NEFH function, the major subunit of the neurofilament complex, reduces proliferation and growth of breast cancer cells and arrests them in Go/G1 phase of the cell cycle along with a reduction in migration and invasion. These findings suggest that DNA methylation-mediated silencing of the neurofilament genes <i>NEFH</i>, <i>NEFM,</i> and <i>NEFL</i> are frequent events that may contribute to the progression of breast cancer and possibly other malignancies.
DOI: 10.6084/m9.figshare.1418252.v1
title: Epigenetic Silencing of Neurofilament Genes Promotes an Aggressive Phenotype in Breast Cancer

description: ABSTRACT<i>Neurofilament heavy polypeptide</i> (<i>NEFH</i>) has recently been identified as a candidate DNA hypermethylated gene within the functional breast cancer hypermethylome. <i>NEFH</i> exists in a complex with <i>neurofilament medium polypeptide</i> (<i>NEFM</i>) and <i>neurofilament light polypeptide</i> (<i>NEFL</i>) to form neurofilaments, which are structural components of the cytoskeleton in mature neurons. Recent studies reported the deregulation of these proteins in several malignancies, suggesting that neurofilaments may have a role in other cell types as well. Using a comprehensive approach, we studied the epigenetic inactivation of neurofilament genes in breast cancer and the functional significance of this event. We report that DNA methylation-associated silencing of <i>NEFH, NEFL</i>, and <i>NEFM</i> in breast cancer is frequent, cancer-specific, and correlates with clinical features of disease progression. DNA methylation-mediated inactivation of these genes occurs also in multiple other cancer histologies including pancreas, gastric, and colon. Restoration of NEFH function, the major subunit of the neurofilament complex, reduces proliferation and growth of breast cancer cells and arrests them in Go/G1 phase of the cell cycle along with a reduction in migration and invasion. These findings suggest that DNA methylation-mediated silencing of the neurofilament genes <i>NEFH, NEFM</i>, and <i>NEFL</i> are frequent events that may contribute to the progression of breast cancer and possibly other malignancies.
DOI: 10.6084/m9.figshare.1418252.v2
title: Epigenetic silencing of neurofilament genes promotes an aggressive phenotype in breast cancer

description: <i>Neurofilament heavy polypeptide</i> (<i>NEFH</i>) has recently been identified as a candidate DNA hypermethylated gene within the functional breast cancer hypermethylome. NEFH exists in a complex with neurofilament medium polypeptide (NEFM) and neurofilament light polypeptide (NEFL) to form neurofilaments, which are structural components of the cytoskeleton in mature neurons. Recent studies reported the deregulation of these proteins in several malignancies, suggesting that neurofilaments may have a role in other cell types as well. Using a comprehensive approach, we studied the epigenetic inactivation of neurofilament genes in breast cancer and the functional significance of this event. We report that DNA methylation-associated silencing of <i>NEFH</i>, <i>NEFL,</i> and <i>NEFM</i> in breast cancer is frequent, cancer-specific, and correlates with clinical features of disease progression. DNA methylation-mediated inactivation of these genes occurs also in multiple other cancer histologies including pancreas, gastric, and colon. Restoration of NEFH function, the major subunit of the neurofilament complex, reduces proliferation and growth of breast cancer cells and arrests them in Go/G1 phase of the cell cycle along with a reduction in migration and invasion. These findings suggest that DNA methylation-mediated silencing of the neurofilament genes <i>NEFH</i>, <i>NEFM,</i> and <i>NEFL</i> are frequent events that may contribute to the progression of breast cancer and possibly other malignancies.
DOI: 10.6084/m9.figshare.1418252.v3
title: Epigenetic silencing of neurofilament genes promotes an aggressive phenotype in breast cancer

description: <i>Neurofilament heavy polypeptide</i> (<i>NEFH</i>) has recently been identified as a candidate DNA hypermethylated gene within the functional breast cancer hypermethylome. NEFH exists in a complex with neurofilament medium polypeptide (NEFM) and neurofilament light polypeptide (NEFL) to form neurofilaments, which are structural components of the cytoskeleton in mature neurons. Recent studies reported the deregulation of these proteins in several malignancies, suggesting that neurofilaments may have a role in other cell types as well. Using a comprehensive approach, we studied the epigenetic inactivation of neurofilament genes in breast cancer and the functional significance of this event. We report that DNA methylation-associated silencing of <i>NEFH</i>, <i>NEFL,</i> and <i>NEFM</i> in breast cancer is frequent, cancer-specific, and correlates with clinical features of disease progression. DNA methylation-mediated inactivation of these genes occurs also in multiple other cancer histologies including pancreas, gastric, and colon. Restoration of NEFH function, the major subunit of the neurofilament complex, reduces proliferation and growth of breast cancer cells and arrests them in Go/G1 phase of the cell cycle along with a reduction in migration and invasion. These findings suggest that DNA methylation-mediated silencing of the neurofilament genes <i>NEFH</i>, <i>NEFM,</i> and <i>NEFL</i> are frequent events that may contribute to the progression of breast cancer and possibly other malignancies.
DOI: 10.6084/m9.figshare.1418261
title: A systematic investigation based on microRNA-mediated gene regulatory network reveals that dysregulation of microRNA-19a/Cyclin D1 axis confers an oncogenic potential and a worse prognosis in human hepatocellular carcinoma

description: MicroRNAs (miRNAs) contribute to a wide variety of human diseases by regulating gene expression, leading to imbalances in gene regulatory networks. To discover novel hepatocellular carcinoma (HCC)-related miRNA-target axes and to elucidate their functions, we here performed a systematic investigation combining biological data acquisition and integration, miRNA-target prediction, network construction, functional assay and clinical validation. As a result, a total of 117 HCC differentially expressed miRNAs were identified, and 728 high confident target genes of these miRNAs were collected. Then, the interaction network of target genes was constructed and 221 key nodes with topological importance in the network were identified according to their topological features including degree, node-betweenness, closeness and K-coreness. Among these key nodes, Cyclin D1 had the highest node-betweenness, implying its bottleneck role in the network. Luciferase reporter assay confirmed that miRNA-19a, which was one of HCC downregulated miRNAs, directly targeted Cyclin D1 in HCC cells. Moreover, miR-19a might play inhibitory roles in HCC malignancy via regulating Cyclin D1 expression. Further clinical evidence also highlighted the prognostic potential of miR-19a/Cyclin D1 axis in HCC. In conclusion, this systematic investigation provides a framework to identify featured miRNAs and their target genes which are potent effectors in the occurrence and development of HCC. More importantly, miR-19a/Cyclin D1 axis might have promising applications as a therapeutic target and a prognostic marker for patients with HCC.