cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.1632854.v1
title: Cost-effectiveness of vortioxetine <i>versus</i> venlafaxine (extended release) in the treatment of major depressive disorder in South Korea

description: ABSTRACT<b><i>Objective</i></b>: To assess the cost-effectiveness of vortioxetine <i>versus</i> venlafaxine XR (extended-release) in major depressive disorder (MDD) patients in South Korea.<b><i>Methods</i></b>: A 1-year cost-effectiveness analysis from a limited societal perspective was performed using a combined model consisting of a decision-tree and a Markov model. Patients entered the model when initiating or switching antidepressant treatment following inadequate response to previous treatment. Remission, relapse and recovery were the main health states.<b><i>Results</i></b>: Vortioxetine dominated venlafaxine XR, with quality-adjusted life year (QALY) gains of 0.0131 and cost savings of KRW 623,229/year [US$530/year] from a limited societal perspective. Safety contributed more than efficacy to the incremental QALY gains. More patients were in recovery after initial treatment and after 1 year with vortioxetine (31%, 40%) compared to venlafaxine XR (23%, 36%). Vortioxetine remained dominant in 98% of probabilistic simulations.<b><i>Conclusion</i></b>: Vortioxetine dominated venlafaxine XR in South Korea and is a relevant treatment option for MDD patients initiating or switching therapy.
DOI: 10.6084/m9.figshare.1632851
title: Rating US reservoirs relative to fish habitat condition

description: Fish habitats in many aging US reservoirs have become degraded and require broad-scale assessment to rate their status and facilitate rehabilitation efforts. To help prioritize habitat projects in reservoirs, we assembled a rating system for large reservoirs in the contiguous United States. Using responses to an online questionnaire about fish habitat impairment in 1299 large US reservoirs, we applied multivariate analyses to identify combinations of habitat impairment descriptors that quantified broad impairment types (i.e., a construct). Resulting constructs reflected point source pollution, nonpoint source pollution, excessive nutrients, algae blooms, siltation, limited nutrients, mudflats and shallowness, limited connectivity to adjacent habitats, limited littoral structure, nuisance species, anomalous water regimes, and large water level fluctuations. Scores were summed across constructs to create a composite number that rated overall reservoir habitat impairment. Construct and composite scores differed among geographic ecoregions of the United States. This rating system could provide a starting point for prioritizing reservoirs for habitat rehabilitation and enhancement projects.
DOI: 10.6084/m9.figshare.1632851.v1
title: Rating US reservoirs relative to fish habitat condition

description: Fish habitats in many aging US reservoirs have become degraded and require broad-scale assessment to rate their status and facilitate rehabilitation efforts. To help prioritize habitat projects in reservoirs, we assembled a rating system for large reservoirs in the contiguous United States. Using responses to an online questionnaire about fish habitat impairment in 1299 large US reservoirs, we applied multivariate analyses to identify combinations of habitat impairment descriptors that quantified broad impairment types (i.e., a construct). Resulting constructs reflected point source pollution, nonpoint source pollution, excessive nutrients, algae blooms, siltation, limited nutrients, mudflats and shallowness, limited connectivity to adjacent habitats, limited littoral structure, nuisance species, anomalous water regimes, and large water level fluctuations. Scores were summed across constructs to create a composite number that rated overall reservoir habitat impairment. Construct and composite scores differed among geographic ecoregions of the United States. This rating system could provide a starting point for prioritizing reservoirs for habitat rehabilitation and enhancement projects.
DOI: 10.6084/m9.figshare.1632852
title: Evaluation of a particle trap laser desorption mass spectrometer (PT-LDMS) for the quantification of sulfate aerosols

description: A particle trap laser desorption mass spectrometer (PT-LDMS) has been developed for the online measurements of the chemical composition of submicron aerosol particles. The PT-LDMS was evaluated by both laboratory and ambient measurements, with the focus being the quantification of sulfate aerosols. Ammonium sulfate ((NH<sub>4</sub>)<sub>2</sub>SO<sub>4</sub>) is generally the predominant form of sulfate aerosols in urban air; hence, it is used as a material for laboratory experiments and calibration. Major fragments of (NH<sub>4</sub>)<sub>2</sub>SO<sub>4</sub> were observed at mass-to-charge ratios (<i>m</i>/<i>z</i>) of 48 (SO<sup>+</sup>) and 64 (SO<sub>2</sub><sup>+</sup>). The dependence of sensitivity (expressed as the ratio of <i>m</i>/<i>z</i> 48 signal to sulfate mass) on laser power and cell temperature was investigated. An intercomparison of PT-LDMS with a commercial sulfate particle analyzer (SPA) and filter sampling was performed in Tokyo. Good agreement was observed between SPA and filter analysis (slope = 0.98, <i>r</i><sup>2</sup> = 0.99). Although the mass concentration of sulfate measured by PT-LDMS exhibited a tight correlation with that measured by SPA, the mass concentration measured by PT-LDMS tended to underestimate that measured by SPA (slope = 0.70, <i>r</i><sup>2</sup> = 0.96). While the discrepancy can be mainly attributed to the difference in size cut between PT-LDMS (approximately PM<sub>1</sub>) and SPA (PM<sub>2.5</sub>), differences in vaporization efficiency were also found to be important. Copyright © 2016 American Association for Aerosol Research
DOI: 10.6084/m9.figshare.1632855.v2
title: The aminoacyl-tRNA synthetases of <i>Drosophila melanogaster</i>

description: Aminoacyl-tRNA synthetases (aaRSs) ligate amino acids to their cognate tRNAs, allowing them to decode the triplet code during translation. Through different mechanisms aaRSs also perform several non-canonical functions in transcription, translation, apoptosis, angiogenesis and inflammation. <i>Drosophila</i> has become a preferred system to model human diseases caused by mutations in <i>aaRS</i> genes, to dissect effects of reduced translation or non-canonical activities, and to study aminoacylation and translational fidelity. However, the lack of a systematic annotation of this gene family has hampered such studies. Here, we report the identification of the entire set of <i>aaRS</i> genes in the fly genome and we predict their roles based on experimental evidence and/or orthology. Further, we propose a new, systematic and logical nomenclature for aaRSs. We also review the research conducted on <i>Drosophila</i> aaRSs to date. Together, our work provides the foundation for further research in the fly aaRS field.
DOI: 10.6084/m9.figshare.1632855.v1
title: The aminoacyl-tRNA synthetases of <i>Drosophila melanogaster</i>

description: Aminoacyl-tRNA synthetases (aaRSs) ligate amino acids to their cognate tRNAs, allowing them to decode the triplet code during translation. Through different mechanisms aaRSs also perform several non-canonical functions in transcription, translation, apoptosis, angiogenesis and inflammation. <i>Drosophila</i> has become a preferred system to model human diseases caused by mutations in <i>aaRS</i> genes, to dissect effects of reduced translation or non-canonical activities, and to study aminoacylation and translational fidelity. However, the lack of a systematic annotation of this gene family has hampered such studies. Here, we report the identification of the entire set of <i>aaRS</i> genes in the fly genome and we predict their roles based on experimental evidence and/or orthology. Further, we propose a new, systematic and logical nomenclature for aaRSs. We also review the research conducted on <i>Drosophila</i> aaRSs to date. Together, our work provides the foundation for further research in the fly aaRS field.
DOI: 10.6084/m9.figshare.1632849.v1
title: A primitive hadrosaurid from southeastern North America and the origin and early evolution of ‘duck-billed’ dinosaurs

description: <i>Eotrachodon orientalis</i> gen. et sp. nov. (latest Santonian of Alabama, southeastern U.S.A.) is one of the oldest and most basal hadrosaurid dinosaurs and the only hadrosaurid from Appalachia (present day eastern North America) with a preserved skull. This taxon possesses a relatively derived narial structure that was until now regarded as synapomorphic for saurolophine (solid-crested or crestless) hadrosaurids. Maximum parsimony analysis places <i>E. orientalis</i> as the sister taxon to Saurolophidae (Saurolophinae + Lambeosaurinae). Character optimization on the phylogeny indicates that the saurolophine-like circumnarial structure evolved by the Santonian following the split between saurolophines and lambeosaurines but prior to the major hadrosaurid radiation. Statistical dispersal-vicariance analysis posits an Appalachian ancestral area for Hadrosauridae and subsequent dispersal of their ancestors into Laramidia (present-day western North America) during the Cenomanian. http://zoobank.org/urn:lsid:zoobank.org:pub:3AD914D2-A3A5-45FD-8C94-5EE80461FEBC SUPPLEMENTAL DATA—Supplemental materials are available for this article for free at www.tandfonline.com/UJVP Citation for this article: Prieto-Márquez, A., G. M. Erickson, and J. A. Ebersole. 2016. A primitive hadrosaurid from southeastern North America and the origin and early evolution of ‘duck-billed’ dinosaurs. Journal of Vertebrate Paleontology. DOI: 10.1080/02724634.2015.1054495
DOI: 10.6084/m9.figshare.1632852.v2
title: Evaluation of a particle trap laser desorption mass spectrometer (PT-LDMS) for the quantification of sulfate aerosols

description: A particle trap laser desorption mass spectrometer (PT-LDMS) has been developed for the online measurements of the chemical composition of submicron aerosol particles. The PT-LDMS was evaluated by both laboratory and ambient measurements, with the focus being the quantification of sulfate aerosols. Ammonium sulfate ((NH<sub>4</sub>)<sub>2</sub>SO<sub>4</sub>) is generally the predominant form of sulfate aerosols in urban air; hence, it is used as a material for laboratory experiments and calibration. Major fragments of (NH<sub>4</sub>)<sub>2</sub>SO<sub>4</sub> were observed at mass-to-charge ratios (<i>m</i>/<i>z</i>) of 48 (SO<sup>+</sup>) and 64 (SO<sub>2</sub><sup>+</sup>). The dependence of sensitivity (expressed as the ratio of <i>m</i>/<i>z</i> 48 signal to sulfate mass) on laser power and cell temperature was investigated. An intercomparison of PT-LDMS with a commercial sulfate particle analyzer (SPA) and filter sampling was performed in Tokyo. Good agreement was observed between SPA and filter analysis (slope = 0.98, <i>r</i><sup>2</sup> = 0.99). Although the mass concentration of sulfate measured by PT-LDMS exhibited a tight correlation with that measured by SPA, the mass concentration measured by PT-LDMS tended to underestimate that measured by SPA (slope = 0.70, <i>r</i><sup>2</sup> = 0.96). While the discrepancy can be mainly attributed to the difference in size cut between PT-LDMS (approximately PM<sub>1</sub>) and SPA (PM<sub>2.5</sub>), differences in vaporization efficiency were also found to be important. Copyright © 2016 American Association for Aerosol Research
DOI: 10.6084/m9.figshare.1632845
title: Autophagy and modular restructuring of metabolism control germline tumor differentiation and proliferation in <i>C. elegans</i>

description: Autophagy can act either as a tumor suppressor or as a survival mechanism for established tumors. To understand how autophagy plays this dual role in cancer, in vivo models are required. By using a highly heterogeneous <i>C. elegans</i> germline tumor, we show that autophagy-related proteins are expressed in a specific subset of tumor cells, neurons. Inhibition of autophagy impairs neuronal differentiation and increases tumor cell number, resulting in a shorter life span of animals with tumors, while induction of autophagy extends their life span by impairing tumor proliferation. Fasting of animals with fully developed tumors leads to a doubling of their life span, which depends on modular changes in transcription including switches in transcription factor networks and mitochondrial metabolism. Hence, our results suggest that metabolic restructuring, cell-type specific regulation of autophagy and neuronal differentiation constitute central pathways preventing growth of heterogeneous tumors.
DOI: 10.6084/m9.figshare.1632845.v1
title: Autophagy and modular restructuring of metabolism control germline tumor differentiation and proliferation in <i>C. elegans</i>

description: Autophagy can act either as a tumor suppressor or as a survival mechanism for established tumors. To understand how autophagy plays this dual role in cancer, in vivo models are required. By using a highly heterogeneous <i>C. elegans</i> germline tumor, we show that autophagy-related proteins are expressed in a specific subset of tumor cells, neurons. Inhibition of autophagy impairs neuronal differentiation and increases tumor cell number, resulting in a shorter life span of animals with tumors, while induction of autophagy extends their life span by impairing tumor proliferation. Fasting of animals with fully developed tumors leads to a doubling of their life span, which depends on modular changes in transcription including switches in transcription factor networks and mitochondrial metabolism. Hence, our results suggest that metabolic restructuring, cell-type specific regulation of autophagy and neuronal differentiation constitute central pathways preventing growth of heterogeneous tumors.
DOI: 10.6084/m9.figshare.1632846
title: Nanoparticles restore lysosomal acidification defects: Implications for Parkinson and other lysosomal-related diseases

description: Lysosomal impairment causes lysosomal storage disorders (LSD) and is involved in pathogenesis of neurodegenerative diseases, notably Parkinson disease (PD). Strategies enhancing or restoring lysosomal-mediated degradation thus appear as tantalizing disease-modifying therapeutics. Here we demonstrate that poly(DL-lactide-<i>co</i>-glycolide) (PLGA) acidic nanoparticles (aNP) restore impaired lysosomal function in a series of toxin and genetic cellular models of PD, i.e. ATP13A2-mutant or depleted cells or glucocerebrosidase (GBA)-mutant cells, as well as in a genetic model of lysosomal-related myopathy. We show that PLGA-aNP are transported to the lysosome within 24 h, lower lysosomal pH and rescue chloroquine (CQ)-induced toxicity. Re-acidification of defective lysosomes following PLGA-aNP treatment restores lysosomal function in different pathological contexts. Finally, our results show that PLGA-aNP may be detected after intracerebral injection in neurons and attenuate PD-related neurodegeneration in vivo by mechanisms involving a rescue of compromised lysosomes.
DOI: 10.6084/m9.figshare.1632846.v2
title: Nanoparticles restore lysosomal acidification defects: Implications for Parkinson and other lysosomal-related diseases

description: Lysosomal impairment causes lysosomal storage disorders (LSD) and is involved in pathogenesis of neurodegenerative diseases, notably Parkinson disease (PD). Strategies enhancing or restoring lysosomal-mediated degradation thus appear as tantalizing disease-modifying therapeutics. Here we demonstrate that poly(DL-lactide-<i>co</i>-glycolide) (PLGA) acidic nanoparticles (aNP) restore impaired lysosomal function in a series of toxin and genetic cellular models of PD, i.e. ATP13A2-mutant or depleted cells or glucocerebrosidase (GBA)-mutant cells, as well as in a genetic model of lysosomal-related myopathy. We show that PLGA-aNP are transported to the lysosome within 24 h, lower lysosomal pH and rescue chloroquine (CQ)-induced toxicity. Re-acidification of defective lysosomes following PLGA-aNP treatment restores lysosomal function in different pathological contexts. Finally, our results show that PLGA-aNP may be detected after intracerebral injection in neurons and attenuate PD-related neurodegeneration in vivo by mechanisms involving a rescue of compromised lysosomes.
DOI: 10.6084/m9.figshare.1632842.v1
title: High-throughput analyses of hnRNP H1 dissects its multi-functional aspect

description: hnRNPs are polyvalent RNA binding proteins that have been implicated in a range of regulatory roles including splicing, mRNA decay, translation, and miRNA metabolism. A variety of genome wide studies have taken advantage of methods like CLIP and RIP to identify the targets and binding sites of RNA binding proteins. However, due to the complex nature of RNA-binding proteins, these studies are incomplete without assays that characterize the impact of RBP binding on mRNA target expression. Here we used a suite of high-throughput approaches (RIP-Seq, iCLIP, RNA-Seq and shotgun proteomics) to provide a comprehensive view of hnRNP H1s ensemble of targets and its role in splicing, mRNA decay, and translation. The combination of RIP-Seq and iCLIP allowed us to identify a set of 1,086 high confidence target transcripts. Binding site motif analysis of these targets suggests the TGGG tetramer as a prevalent component of hnRNP H1 binding motif, with particular enrichment around intronic hnRNP H1 sites. Our analysis of the target transcripts and binding sites indicates that hnRNP H1s involvement in splicing is 2-fold: it directly affects a substantial number of splicing events, but also regulates the expression of major components of the splicing machinery and other RBPs with known roles in splicing regulation. The identified mRNA targets displayed function enrichment in MAPK signaling and ubiquitin mediated proteolysis, which might be main routes by which hnRNP H1 promotes tumorigenesis.
DOI: 10.6084/m9.figshare.1632843
title: <i>Drosophila</i> Mitf regulates the V-ATPase and the lysosomal-autophagic pathway

description: An evolutionarily conserved gene network regulates the expression of genes involved in lysosome biogenesis, autophagy, and lipid metabolism. In mammals, TFEB and other members of the MiTF-TFE family of transcription factors control this network. Here we report that the lysosomal-autophagy pathway is controlled by <i>Mitf</i> gene in <i>Drosophila melanogaster</i>. Mitf is the single MiTF-TFE family member in <i>Drosophila</i> and prior to this work was known only for its function in eye development. We show that Mitf regulates the expression of genes encoding V-ATPase subunits as well as many additional genes involved in the lysosomal-autophagy pathway. Reduction of Mitf function leads to abnormal lysosomes and impairs autophagosome fusion and lipid breakdown during the response to starvation. In contrast, elevated Mitf levels increase the number of lysosomes, autophagosomes and autolysosomes, and decrease the size of lipid droplets. Inhibition of <i>Drosophila</i> MTORC1 induces Mitf translocation to the nucleus, underscoring conserved regulatory mechanisms between <i>Drosophila</i> and mammalian systems. Furthermore, we show Mitf-mediated clearance of cytosolic and nuclear expanded ATXN1 (ataxin 1) in a cellular model of spinocerebellar ataxia type 1 (SCA1). This remarkable observation illustrates the potential of the lysosomal-autophagy system to prevent toxic protein aggregation in both the cytoplasmic and nuclear compartments. We anticipate that the genetics of the <i>Drosophila</i> model and the absence of redundant MIT transcription factors will be exploited to investigate the regulation and function of the lysosomal-autophagy gene network.
DOI: 10.6084/m9.figshare.1632843.v1
title: <i>Drosophila</i> Mitf regulates the V-ATPase and the lysosomal-autophagic pathway

description: An evolutionarily conserved gene network regulates the expression of genes involved in lysosome biogenesis, autophagy, and lipid metabolism. In mammals, TFEB and other members of the MiTF-TFE family of transcription factors control this network. Here we report that the lysosomal-autophagy pathway is controlled by <i>Mitf</i> gene in <i>Drosophila melanogaster</i>. Mitf is the single MiTF-TFE family member in <i>Drosophila</i> and prior to this work was known only for its function in eye development. We show that Mitf regulates the expression of genes encoding V-ATPase subunits as well as many additional genes involved in the lysosomal-autophagy pathway. Reduction of Mitf function leads to abnormal lysosomes and impairs autophagosome fusion and lipid breakdown during the response to starvation. In contrast, elevated Mitf levels increase the number of lysosomes, autophagosomes and autolysosomes, and decrease the size of lipid droplets. Inhibition of <i>Drosophila</i> MTORC1 induces Mitf translocation to the nucleus, underscoring conserved regulatory mechanisms between <i>Drosophila</i> and mammalian systems. Furthermore, we show Mitf-mediated clearance of cytosolic and nuclear expanded ATXN1 (ataxin 1) in a cellular model of spinocerebellar ataxia type 1 (SCA1). This remarkable observation illustrates the potential of the lysosomal-autophagy system to prevent toxic protein aggregation in both the cytoplasmic and nuclear compartments. We anticipate that the genetics of the <i>Drosophila</i> model and the absence of redundant MIT transcription factors will be exploited to investigate the regulation and function of the lysosomal-autophagy gene network.
DOI: 10.6084/m9.figshare.1632844.v2
title: Spatial regulation of greatwall by Cdk1 and PP2A-Tws in the cell cycle

description: Entry into mitosis requires the phosphorylation of multiple substrates by cyclin B-Cdk1, while exit from mitosis requires their dephosphorylation, which depends largely on the phosphatase PP2A in complex with its B55 regulatory subunit (Tws in Drosophila). At mitotic entry, cyclin B-Cdk1 activates the Greatwall kinase, which phosphorylates Endosulfine proteins, thereby activating their ability to inhibit PP2A-B55 competitively. The inhibition of PP2A-B55 at mitotic entry facilitates the accumulation of phosphorylated Cdk1 substrates. The coordination of these enzymes involves major changes in their localization. In interphase, Gwl is nuclear while PP2A-B55 is cytoplasmic. We recently showed that Gwl suddenly relocalizes from the nucleus to the cytoplasm in prophase, before nuclear envelope breakdown and that this controlled localization of Gwl is required for its function. We and others have shown that phosphorylation of Gwl by cyclin B-Cdk1 at multiple sites is required for its nuclear exclusion, but the precise mechanisms remained unclear. In addition, how Gwl returns to its nuclear localization was not explored. Here we show that cyclin B-Cdk1 directly inactivates a Nuclear Localization Signal in the central region of Gwl. This phosphorylation facilitates the cytoplasmic retention of Gwl, which is exported to the cytoplasm in a Crm1-dependent manner. In addition, we show that PP2A-Tws promotes the return of Gwl to its nuclear localization during cytokinesis. Our results indicate that the cyclic changes in Gwl localization at mitotic entry and exit are directly regulated by the antagonistic cyclin B-Cdk1 and PP2A-Tws enzymes.