cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.1282588.v4
title: Multiple functions of the SNARE protein Snap29 in autophagy, endocytic, and exocytic trafficking during epithelial formation in <i>Drosophila</i>

description: How autophagic degradation is linked to endosomal trafficking routes is little known. Here we screened a collection of uncharacterized <i>Drosophila</i> mutants affecting membrane transport to identify new genes that also have a role in autophagy. We isolated a loss of function mutant in <i>Snap29</i> (<i>Synaptosomal-associated protein 29 kDa</i>)<i>,</i> the gene encoding the <i>Drosophila</i> homolog of the human protein SNAP29 and have characterized its function <i>in vivo</i>. Snap29 contains 2 soluble NSF attachment protein receptor (SNARE) domains and a asparagine-proline-phenylalanine (NPF motif) at its N terminus and rescue experiments indicate that both SNARE domains are required for function, whereas the NPF motif is in part dispensable. We find that Snap29 interacts with SNARE proteins, localizes to multiple trafficking organelles, and is required for protein trafficking and for proper Golgi apparatus morphology. Developing tissue lacking Snap29 displays distinctive epithelial architecture defects and accumulates large amounts of autophagosomes, highlighting a major role of Snap29 in autophagy and secretion. Mutants for autophagy genes do not display epithelial architecture or secretion defects, suggesting that the these alterations of the <i>Snap29</i> mutant are unlikely to be caused by the impairment of autophagy. In contrast, we find evidence of elevated levels of hop-Stat92E (hopscotch-signal transducer and activator of transcription protein at 92E) ligand, receptor, and associated signaling, which might underlie the epithelial defects. In summary, our findings support a role of Snap29 at key steps of membrane trafficking, and predict that signaling defects may contribute to the pathogenesis of cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma (CEDNIK), a human congenital syndrome due to loss of Snap29.
DOI: 10.6084/m9.figshare.1282587.v2
title: Cell-cycle fate-monitoring distinguishes individual chemosensitive and chemoresistant cancer cells in drug-treated heterogeneous populations demonstrated by real-time FUCCI imaging

description: Essentially every population of cancer cells within a tumor is heterogeneous, especially with regard to chemosensitivity and resistance. In the present study, we utilized the fluorescence ubiquitination-based cell cycle indicator (FUCCI) imaging system to investigate the correlation between cell-cycle behavior and apoptosis after treatment of cancer cells with chemotherapeutic drugs. HeLa cells expressing FUCCI were treated with doxorubicin (DOX) (5 μM) or cisplatinum (CDDP) (5 μM) for 3 h. Cell-cycle progression and apoptosis were monitored by time-lapse FUCCI imaging for 72 h. Time-lapse FUCCI imaging demonstrated that both DOX and CDDP could induce cell cycle arrest in S/G<sub>2</sub>/M in almost all the cells, but a subpopulation of the cells could escape the block and undergo mitosis. The subpopulation which went through mitosis subsequently underwent apoptosis, while the cells arrested in S/G<sub>2</sub>/M survived. The present results demonstrate that chemoresistant cells can be readily identified in a heterogeneous population of cancer cells by S/G<sub>2</sub>/M arrest, which can serve in future studies as a visible target for novel agents that kill cell-cycle-arrested cells.
DOI: 10.6084/m9.figshare.1282589
title: Loss of functional MYO1C/myosin 1c, a motor protein involved in lipid raft trafficking, disrupts autophagosome-lysosome fusion

description: MYO1C, a single-headed class I myosin, associates with cholesterol-enriched lipid rafts and facilitates their recycling from intracellular compartments to the cell surface. Absence of functional MYO1C disturbs the cellular distribution of lipid rafts, causes the accumulation of cholesterol-enriched membranes in the perinuclear recycling compartment, and leads to enlargement of endolysosomal membranes. Several feeder pathways, including classical endocytosis but also the autophagy pathway, maintain the health of the cell by selective degradation of cargo through fusion with the lysosome. Here we show that loss of functional MYO1C leads to an increase in total cellular cholesterol and its disrupted subcellular distribution. We observe an accumulation of autophagic structures caused by a block in fusion with the lysosome and a defect in autophagic cargo degradation. Interestingly, the loss of MYO1C has no effect on degradation of endocytic cargo such as EGFR, illustrating that although the endolysosomal compartment is enlarged in size, it is functional, contains active hydrolases, and the correct pH. Our results highlight the importance of correct lipid composition in autophagosomes and lysosomes to enable them to fuse. Ablating MYO1C function causes abnormal cholesterol distribution, which has a major selective impact on the autophagy pathway.
DOI: 10.6084/m9.figshare.1282589.v2
title: Loss of functional MYO1C/myosin 1c, a motor protein involved in lipid raft trafficking, disrupts autophagosome-lysosome fusion

description: MYO1C, a single-headed class I myosin, associates with cholesterol-enriched lipid rafts and facilitates their recycling from intracellular compartments to the cell surface. Absence of functional MYO1C disturbs the cellular distribution of lipid rafts, causes the accumulation of cholesterol-enriched membranes in the perinuclear recycling compartment, and leads to enlargement of endolysosomal membranes. Several feeder pathways, including classical endocytosis but also the autophagy pathway, maintain the health of the cell by selective degradation of cargo through fusion with the lysosome. Here we show that loss of functional MYO1C leads to an increase in total cellular cholesterol and its disrupted subcellular distribution. We observe an accumulation of autophagic structures caused by a block in fusion with the lysosome and a defect in autophagic cargo degradation. Interestingly, the loss of MYO1C has no effect on degradation of endocytic cargo such as EGFR, illustrating that although the endolysosomal compartment is enlarged in size, it is functional, contains active hydrolases, and the correct pH. Our results highlight the importance of correct lipid composition in autophagosomes and lysosomes to enable them to fuse. Ablating MYO1C function causes abnormal cholesterol distribution, which has a major selective impact on the autophagy pathway.
DOI: 10.6084/m9.figshare.1282588.v3
title: Multiple functions of the SNARE protein Snap29 in autophagy, endocytic, and exocytic trafficking during epithelial formation in <i>Drosophila</i>

description: How autophagic degradation is linked to endosomal trafficking routes is little known. Here we screened a collection of uncharacterized <i>Drosophila</i> mutants affecting membrane transport to identify new genes that also have a role in autophagy. We isolated a loss of function mutant in <i>Snap29</i> (<i>Synaptosomal-associated protein 29 kDa</i>)<i>,</i> the gene encoding the <i>Drosophila</i> homolog of the human protein SNAP29 and have characterized its function <i>in vivo</i>. Snap29 contains 2 soluble NSF attachment protein receptor (SNARE) domains and a asparagine-proline-phenylalanine (NPF motif) at its N terminus and rescue experiments indicate that both SNARE domains are required for function, whereas the NPF motif is in part dispensable. We find that Snap29 interacts with SNARE proteins, localizes to multiple trafficking organelles, and is required for protein trafficking and for proper Golgi apparatus morphology. Developing tissue lacking Snap29 displays distinctive epithelial architecture defects and accumulates large amounts of autophagosomes, highlighting a major role of Snap29 in autophagy and secretion. Mutants for autophagy genes do not display epithelial architecture or secretion defects, suggesting that the these alterations of the <i>Snap29</i> mutant are unlikely to be caused by the impairment of autophagy. In contrast, we find evidence of elevated levels of hop-Stat92E (hopscotch-signal transducer and activator of transcription protein at 92E) ligand, receptor, and associated signaling, which might underlie the epithelial defects. In summary, our findings support a role of Snap29 at key steps of membrane trafficking, and predict that signaling defects may contribute to the pathogenesis of cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma (CEDNIK), a human congenital syndrome due to loss of Snap29.
DOI: 10.6084/m9.figshare.1282589.v4
title: Loss of functional MYO1C/myosin 1c, a motor protein involved in lipid raft trafficking, disrupts autophagosome-lysosome fusion

description: MYO1C, a single-headed class I myosin, associates with cholesterol-enriched lipid rafts and facilitates their recycling from intracellular compartments to the cell surface. Absence of functional MYO1C disturbs the cellular distribution of lipid rafts, causes the accumulation of cholesterol-enriched membranes in the perinuclear recycling compartment, and leads to enlargement of endolysosomal membranes. Several feeder pathways, including classical endocytosis but also the autophagy pathway, maintain the health of the cell by selective degradation of cargo through fusion with the lysosome. Here we show that loss of functional MYO1C leads to an increase in total cellular cholesterol and its disrupted subcellular distribution. We observe an accumulation of autophagic structures caused by a block in fusion with the lysosome and a defect in autophagic cargo degradation. Interestingly, the loss of MYO1C has no effect on degradation of endocytic cargo such as EGFR, illustrating that although the endolysosomal compartment is enlarged in size, it is functional, contains active hydrolases, and the correct pH. Our results highlight the importance of correct lipid composition in autophagosomes and lysosomes to enable them to fuse. Ablating MYO1C function causes abnormal cholesterol distribution, which has a major selective impact on the autophagy pathway.
DOI: 10.6084/m9.figshare.1282589.v3
title: Loss of functional MYO1C/myosin 1c, a motor protein involved in lipid raft trafficking, disrupts autophagosome-lysosome fusion

description: MYO1C, a single-headed class I myosin, associates with cholesterol-enriched lipid rafts and facilitates their recycling from intracellular compartments to the cell surface. Absence of functional MYO1C disturbs the cellular distribution of lipid rafts, causes the accumulation of cholesterol-enriched membranes in the perinuclear recycling compartment, and leads to enlargement of endolysosomal membranes. Several feeder pathways, including classical endocytosis but also the autophagy pathway, maintain the health of the cell by selective degradation of cargo through fusion with the lysosome. Here we show that loss of functional MYO1C leads to an increase in total cellular cholesterol and its disrupted subcellular distribution. We observe an accumulation of autophagic structures caused by a block in fusion with the lysosome and a defect in autophagic cargo degradation. Interestingly, the loss of MYO1C has no effect on degradation of endocytic cargo such as EGFR, illustrating that although the endolysosomal compartment is enlarged in size, it is functional, contains active hydrolases, and the correct pH. Our results highlight the importance of correct lipid composition in autophagosomes and lysosomes to enable them to fuse. Ablating MYO1C function causes abnormal cholesterol distribution, which has a major selective impact on the autophagy pathway.
DOI: 10.6084/m9.figshare.1282585.v1
title: miR-23a and miR-125b regulate neural stem/progenitor cell proliferation by targeting Musashi1

description: Musashi1 is an RNA binding protein that controls the neural cell fate, being involved in maintaining neural progenitors in their proliferative state. In particular, its downregulation is needed for triggering early neural differentiation programs. In this study, we profiled microRNA expression during the transition from neural progenitors to differentiated astrocytes and underscored two upregulated microRNAs, miR-23a and miR-125b, that sinergically act to restrain Musashi1 expression, thus creating a regulatory module controlling neural progenitor proliferation.
DOI: 10.6084/m9.figshare.1282587.v3
title: Cell-cycle fate-monitoring distinguishes individual chemosensitive and chemoresistant cancer cells in drug-treated heterogeneous populations demonstrated by real-time FUCCI imaging

description: Essentially every population of cancer cells within a tumor is heterogeneous, especially with regard to chemosensitivity and resistance. In the present study, we utilized the fluorescence ubiquitination-based cell cycle indicator (FUCCI) imaging system to investigate the correlation between cell-cycle behavior and apoptosis after treatment of cancer cells with chemotherapeutic drugs. HeLa cells expressing FUCCI were treated with doxorubicin (DOX) (5 μM) or cisplatinum (CDDP) (5 μM) for 3 h. Cell-cycle progression and apoptosis were monitored by time-lapse FUCCI imaging for 72 h. Time-lapse FUCCI imaging demonstrated that both DOX and CDDP could induce cell cycle arrest in S/G<sub>2</sub>/M in almost all the cells, but a subpopulation of the cells could escape the block and undergo mitosis. The subpopulation which went through mitosis subsequently underwent apoptosis, while the cells arrested in S/G<sub>2</sub>/M survived. The present results demonstrate that chemoresistant cells can be readily identified in a heterogeneous population of cancer cells by S/G<sub>2</sub>/M arrest, which can serve in future studies as a visible target for novel agents that kill cell-cycle-arrested cells.
DOI: 10.6084/m9.figshare.1282585.v2
title: Mir-23a and mir-125b regulate neural stem/progenitor cell proliferation by targeting Musashi1

description: Musashi1 is an RNA binding protein that controls the neural cell fate, being involved in maintaining neural progenitors in their proliferative state. In particular, its downregulation is needed for triggering early neural differentiation programs. In this study, we profiled microRNA expression during the transition from neural progenitors to differentiated astrocytes and underscored 2 upregulated microRNAs, miR-23a and miR-125b, that sinergically act to restrain Musashi1 expression, thus creating a regulatory module controlling neural progenitor proliferation.
DOI: 10.6084/m9.figshare.1282585.v4
title: Mir-23a and mir-125b regulate neural stem/progenitor cell proliferation by targeting Musashi1

description: Musashi1 is an RNA binding protein that controls the neural cell fate, being involved in maintaining neural progenitors in their proliferative state. In particular, its downregulation is needed for triggering early neural differentiation programs. In this study, we profiled microRNA expression during the transition from neural progenitors to differentiated astrocytes and underscored 2 upregulated microRNAs, miR-23a and miR-125b, that sinergically act to restrain Musashi1 expression, thus creating a regulatory module controlling neural progenitor proliferation.
DOI: 10.6084/m9.figshare.1282587.v5
title: Cell-cycle fate-monitoring distinguishes individual chemosensitive and chemoresistant cancer cells in drug-treated heterogeneous populations demonstrated by real-time FUCCI imaging

description: Essentially every population of cancer cells within a tumor is heterogeneous, especially with regard to chemosensitivity and resistance. In the present study, we utilized the fluorescence ubiquitination-based cell cycle indicator (FUCCI) imaging system to investigate the correlation between cell-cycle behavior and apoptosis after treatment of cancer cells with chemotherapeutic drugs. HeLa cells expressing FUCCI were treated with doxorubicin (DOX) (5 μM) or cisplatinum (CDDP) (5 μM) for 3 h. Cell-cycle progression and apoptosis were monitored by time-lapse FUCCI imaging for 72 h. Time-lapse FUCCI imaging demonstrated that both DOX and CDDP could induce cell cycle arrest in S/G<sub>2</sub>/M in almost all the cells, but a subpopulation of the cells could escape the block and undergo mitosis. The subpopulation which went through mitosis subsequently underwent apoptosis, while the cells arrested in S/G<sub>2</sub>/M survived. The present results demonstrate that chemoresistant cells can be readily identified in a heterogeneous population of cancer cells by S/G<sub>2</sub>/M arrest, which can serve in future studies as a visible target for novel agents that kill cell-cycle-arrested cells.
DOI: 10.6084/m9.figshare.1282587.v4
title: Cell-cycle fate-monitoring distinguishes individual chemosensitive and chemoresistant cancer cells in drug-treated heterogeneous populations demonstrated by real-time FUCCI imaging

description: Essentially every population of cancer cells within a tumor is heterogeneous, especially with regard to chemosensitivity and resistance. In the present study, we utilized the fluorescence ubiquitination-based cell cycle indicator (FUCCI) imaging system to investigate the correlation between cell-cycle behavior and apoptosis after treatment of cancer cells with chemotherapeutic drugs. HeLa cells expressing FUCCI were treated with doxorubicin (DOX) (5 μM) or cisplatinum (CDDP) (5 μM) for 3 h. Cell-cycle progression and apoptosis were monitored by time-lapse FUCCI imaging for 72 h. Time-lapse FUCCI imaging demonstrated that both DOX and CDDP could induce cell cycle arrest in S/G<sub>2</sub>/M in almost all the cells, but a subpopulation of the cells could escape the block and undergo mitosis. The subpopulation which went through mitosis subsequently underwent apoptosis, while the cells arrested in S/G<sub>2</sub>/M survived. The present results demonstrate that chemoresistant cells can be readily identified in a heterogeneous population of cancer cells by S/G<sub>2</sub>/M arrest, which can serve in future studies as a visible target for novel agents that kill cell-cycle-arrested cells.
DOI: 10.6084/m9.figshare.1282585.v3
title: Mir-23a and mir-125b regulate neural stem/progenitor cell proliferation by targeting Musashi1

description: Musashi1 is an RNA binding protein that controls the neural cell fate, being involved in maintaining neural progenitors in their proliferative state. In particular, its downregulation is needed for triggering early neural differentiation programs. In this study, we profiled microRNA expression during the transition from neural progenitors to differentiated astrocytes and underscored 2 upregulated microRNAs, miR-23a and miR-125b, that sinergically act to restrain Musashi1 expression, thus creating a regulatory module controlling neural progenitor proliferation.
DOI: 10.6084/m9.figshare.1282563
title: Zinc(II) Complexes of Acetophenone and 5-Chloro-2-hydroxy-benzophenone Thiosemicarbazones. Synthesis, Characterization, and Nonlinear Optical Properties from Quantum Chemical Calculations

description: GRAPHICAL ABSTRACT
DOI: 10.6084/m9.figshare.1282563.v2
title: Zinc(II) Complexes of Acetophenone and 5-Chloro-2-hydroxy-benzophenone Thiosemicarbazones. Synthesis, Characterization, and Nonlinear Optical Properties from Quantum Chemical Calculations

description: GRAPHICAL ABSTRACT
DOI: 10.6084/m9.figshare.1282562
title: Synthesis of Tris(Arylthio)-1,3-Butadienes by Nucleophilic Vinylic Substitution of Polyhalogenated Nitrodienes and Structural Elucidation of the Products

description: GRAPHICAL ABSTRACT
DOI: 10.6084/m9.figshare.1282563.v1
title: Zinc(II) Complexes of Acetophenone and 5-Chloro-2-Hydroxy-Benzophenone Thiosemicarbazones. Synthesis, Characterization, and Nonlinear Optical Properties from Quantum Chemical Calculations

description: GRAPHICAL ABSTRACT
DOI: 10.6084/m9.figshare.1282562.v2
title: Synthesis of Tris(Arylthio)-1,3-Butadienes by Nucleophilic Vinylic Substitution of Polyhalogenated Nitrodienes and Structural Elucidation of the Products

description: GRAPHICAL ABSTRACT
DOI: 10.6084/m9.figshare.1282562.v1
title: Synthesis of Tris(Arylthio)-1,3-Butadienes by Nucleophilic Vinylic Substitution of Polyhalogenated Nitrodienes and Structural Elucidation of the Products

description: GRAPHICAL ABSTRACT
DOI: 10.6084/m9.figshare.1282530
title: Genome-wide analysis of <i>in vivo</i> TRF1 binding to chromatin restricts its location exclusively to telomeric repeats

description: Telomeres are nucleoprotein structures at the ends of eukaryotic chromosomes that protect them from degradation, end-to-end fusions, and fragility. In mammals, telomeres are composed of TTAGGG tandem repeats bound by a protein complex called shelterin, which has fundamental roles in the regulation of telomere protection and length. The telomeric repeat binding factor 1 (TERF1 or TRF1) is one of the components of shelterin and has been shown to be essential for telomere protection. Telomeric repeats can also be found throughout the genome, as Internal or Interstitial Telomeric Sequences (ITSs). Some of the components of shelterin have been described to bind to ITSs as well as other extra-telomeric regions, which in the case of RAP1 exert a key role in transcriptional regulation. Here, we set to address whether TRF1 can be found at extra-telomeric sites both under normal conditions and upon induction of telomere shortening. In particular, we performed a ChIP-sequencing technique to map TRF1 binding sites in MEFs wild-type and deficient for the telomerase RNA component (<i>Terc<sup>−/−</sup></i>), with increasingly short telomeres. Our findings indicate that TRF1 is exclusively located at telomeres both under normal conditions, as well as under extreme telomere shortening. These results indicate that in mice not all members of shelterin have extra-telomeric roles as it was described for RAP1.
DOI: 10.6084/m9.figshare.1282530.v2
title: Genome-wide analysis of <i>in vivo</i> TRF1 binding to chromatin restricts its location exclusively to telomeric repeats

description: Telomeres are nucleoprotein structures at the ends of eukaryotic chromosomes that protect them from degradation, end-to-end fusions, and fragility. In mammals, telomeres are composed of TTAGGG tandem repeats bound by a protein complex called shelterin, which has fundamental roles in the regulation of telomere protection and length. The telomeric repeat binding factor 1 (TERF1 or TRF1) is one of the components of shelterin and has been shown to be essential for telomere protection. Telomeric repeats can also be found throughout the genome, as Internal or Interstitial Telomeric Sequences (ITSs). Some of the components of shelterin have been described to bind to ITSs as well as other extra-telomeric regions, which in the case of RAP1 exert a key role in transcriptional regulation. Here, we set to address whether TRF1 can be found at extra-telomeric sites both under normal conditions and upon induction of telomere shortening. In particular, we performed a ChIP-sequencing technique to map TRF1 binding sites in MEFs wild-type and deficient for the telomerase RNA component (<i>Terc<sup>−/−</sup></i>), with increasingly short telomeres. Our findings indicate that TRF1 is exclusively located at telomeres both under normal conditions, as well as under extreme telomere shortening. These results indicate that in mice not all members of shelterin have extra-telomeric roles as it was described for RAP1.