cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.3510203.v2
title: iLIR database: A web resource for LIR motif-containing proteins in eukaryotes

description: Atg8-family proteins are the best-studied proteins of the core autophagic machinery. They are essential for the elongation and closure of the phagophore into a proper autophagosome. Moreover, Atg8-family proteins are associated with the phagophore from the initiation of the autophagic process to, or just prior to, the fusion between autophagosomes with lysosomes. In addition to their implication in autophagosome biogenesis, they are crucial for selective autophagy through their ability to interact with selective autophagy receptor proteins necessary for the specific targeting of substrates for autophagic degradation. In the past few years it has been revealed that Atg8-interacting proteins include not only receptors but also components of the core autophagic machinery, proteins associated with vesicles and their transport, and specific proteins that are selectively degraded by autophagy. Atg8-interacting proteins contain a short linear LC3-interacting region/LC3 recognition sequence/Atg8-interacting motif (LIR/LRS/AIM) motif which is responsible for their interaction with Atg8-family proteins. These proteins are referred to as LIR-containing proteins (LIRCPs). So far, many experimental efforts have been carried out to identify new LIRCPs, leading to the characterization of some of them in the past 10 years. Given the need for the identification of LIRCPs in various organisms, we developed the iLIR database (https://ilir.warwick.ac.uk) as a freely available web resource, listing all the putative canonical LIRCPs identified in silico in the proteomes of 8 model organisms using the iLIR server, combined with a Gene Ontology (GO) term analysis. Additionally, a curated text-mining analysis of the literature permitted us to identify novel putative LICRPs in mammals that have not previously been associated with autophagy.
DOI: 10.6084/m9.figshare.3510203.v1
title: iLIR database: a web resource for LIR motif-containing proteins in eukaryotes

description: Atg8-family proteins are the best-studied proteins of the core autophagic machinery. They are essential for the elongation and closure of the phagophore into a proper autophagosome. Moreover, Atg8-family proteins are associated with the phagophore from the initiation of the autophagic process to, or just prior to, the fusion between autophagosomes with lysosomes. In addition to their implication in autophagosome biogenesis, they are crucial for selective autophagy through their ability to interact with selective autophagy receptor proteins necessary for the specific targeting of substrates for autophagic degradation. In the last few years it has been revealed that Atg8-interacting proteins include not only receptors but also components of the core autophagic machinery, proteins associated with vesicles and their transport, and specific proteins that are selectively degraded by autophagy. Atg8-interacting proteins contain a short linear LC3-interacting region/LC3 recognition sequence/Atg8-interacting motif (LIR/LRS/AIM) motif which is responsible for their interaction with Atg8-family proteins. These proteins are referred as LIR-containing proteins (LIRCPs). So far, many experimental efforts have been carried out to identify new LIRCPs, leading to the characterization of some of them in the past 10 years. Given the need for the identification of LIRCPs in various organisms, we developed the iLIR database (https://ilir.warwick.ac.uk) as a freely available web resource, listing all the putative canonical LIRCPs identified <i>in silico</i> in the proteomes of 8 model organisms using the iLIR server, combined with a Gene Ontology (GO) term analysis. Additionally, a curated text-mining analysis of the literature permitted us to identify novel putative LICRPs in mammals that have not previously been associated with autophagy.
DOI: 10.6084/m9.figshare.3510200
title: Spatiotemporal dynamics of autophagy receptors in selective mitophagy

description: Damaged mitochondria are turned over through a process of selective autophagy termed mitophagy. In mitophagy, unhealthy mitochondria are recognized and ubiquitinated by Parkinson disease-linked proteins PINK1 and PARK2. The subsequent recruitment of ubiquitin-binding autophagy receptors leads in turn to the sequestration of the damaged organelles into LC3-positive phagophores, precursors to autophagosomes. The precise identity of these receptors and how they are regulated has been the focus of considerable attention. Our recent work uses live-cell imaging to explore the dynamics and regulation of autophagy receptor recruitment. Utilizing multiple paradigms to induce mitochondrial damage, we identified the rapid, 2-step recruitment of autophagy receptors OPTN, CALCOCO2/NDP52, and TAX1BP1. All 3 receptors are recruited to damaged mitochondria with similar kinetics; however, only OPTN is necessary for efficient formation of a phagophore sequestering damaged mitochondria from the cytosol. OPTN is co-recruited to damaged mitochondria along with its upstream kinase TBK1. Depletion of OPTN or TBK1, or expression of amyotrophic lateral sclerosis (ALS)-linked mutations in either protein, interfere with efficient autophagic engulfment of depolarized mitochondria. These observations suggest that insufficient autophagy of damaged mitochondria may contribute to neurodegenerative disease.
DOI: 10.6084/m9.figshare.3510200.v1
title: Spatiotemporal dynamics of autophagy receptors in selective mitophagy

description: Damaged mitochondria are turned over through a process of selective autophagy termed mitophagy. In mitophagy, unhealthy mitochondria are recognized and ubiquitinated by Parkinson disease-linked proteins PINK1 and PARK2. The subsequent recruitment of ubiquitin-binding autophagy receptors leads in turn to the sequestration of the damaged organelles into LC3-positive phagophores, precursors to autophagosomes. The precise identity of these receptors and how they are regulated has been the focus of considerable attention. Our recent work uses live-cell imaging to explore the dynamics and regulation of autophagy receptor recruitment. Utilizing multiple paradigms to induce mitochondrial damage, we identified the rapid, 2-step recruitment of autophagy receptors OPTN, CALCOCO2/NDP52, and TAX1BP1. All 3 receptors are recruited to damaged mitochondria with similar kinetics; however, only OPTN is necessary for efficient formation of a phagophore sequestering damaged mitochondria from the cytosol. OPTN is co-recruited to damaged mitochondria along with its upstream kinase TBK1. Depletion of OPTN or TBK1, or expression of amyotrophic lateral sclerosis (ALS)-linked mutations in either protein, interfere with efficient autophagic engulfment of depolarized mitochondria. These observations suggest that insufficient autophagy of damaged mitochondria may contribute to neurodegenerative disease.
DOI: 10.6084/m9.figshare.3510017
title: Transcriptional effects of metal-rich acid drainage water from the abandoned Løkken Mine on Atlantic salmon (<i>Salmo salar</i>) smolt

description: Runoff of metals represents one of the major environmental challenges related to historic and ongoing mining activity. In this study, transcriptomics (direct RNA sequencing [RNA-seq] and reverse-transcription quantitative polymerase chain reaction [RT-qPCR]) was used to predict toxicity of metal-rich acid mine drainage (AMD) water collected in the abandoned copper (Cu) mine called Løkken Mine on Atlantic salmon liver and kidney, the main target organs of Cu-induced toxicity in fish. Smolts were exposed to control and diluted AMD water, which contains a mixture of metals but is especially enriched with Cu, at 4 concentrations in freshwater (FW) for 96 h, and then were transferred to and kept in seawater (SW) for another 24 h. Significant accumulation of Cu was observed in the gills, but not liver and kidney tissues, after 96 h of exposure. Short-term exposure to metal-rich ADM (high exposure group) significantly upregulated 3201 transcripts and downregulated 3782 transcripts in liver. The strongest effect attributed to exposure was observed on the KEGG pathway “protein processing in endoplasmic reticulum,” followed by “steroid biosynthesis.” Gene ontology (GO) analysis suggested that exposure predominantly affected “protein folding,” possibly by disrupting disulfide bonds as a result of endoplasmic-reticulum-generated stress, and “sterol biosynthetic processes.” Transfer to uncontaminated SW for 24 h amended the transcription of several genes, suggesting a transient effect of treatment on some mechanisms. In conclusion, the data show that trace metals in AMD from abandoned pyrite mines might disturb molecular mechanisms linked to protein folding in Atlantic salmon smolt endoplasmic reticulum.
DOI: 10.6084/m9.figshare.3510017.v1
title: Transcriptional effects of metal-rich acid drainage water from the abandoned Løkken Mine on Atlantic salmon (<i>Salmo salar</i>) smolt

description: Runoff of metals represents one of the major environmental challenges related to historic and ongoing mining activity. In this study, transcriptomics (direct RNA sequencing [RNA-seq] and reverse-transcription quantitative polymerase chain reaction [RT-qPCR]) was used to predict toxicity of metal-rich acid mine drainage (AMD) water collected in the abandoned copper (Cu) mine called Løkken Mine on Atlantic salmon liver and kidney, the main target organs of Cu-induced toxicity in fish. Smolts were exposed to control and diluted AMD water, which contains a mixture of metals but is especially enriched with Cu, at 4 concentrations in freshwater (FW) for 96 h, and then were transferred to and kept in seawater (SW) for another 24 h. Significant accumulation of Cu was observed in the gills, but not liver and kidney tissues, after 96 h of exposure. Short-term exposure to metal-rich ADM (high exposure group) significantly upregulated 3201 transcripts and downregulated 3782 transcripts in liver. The strongest effect attributed to exposure was observed on the KEGG pathway “protein processing in endoplasmic reticulum,” followed by “steroid biosynthesis.” Gene ontology (GO) analysis suggested that exposure predominantly affected “protein folding,” possibly by disrupting disulfide bonds as a result of endoplasmic-reticulum-generated stress, and “sterol biosynthetic processes.” Transfer to uncontaminated SW for 24 h amended the transcription of several genes, suggesting a transient effect of treatment on some mechanisms. In conclusion, the data show that trace metals in AMD from abandoned pyrite mines might disturb molecular mechanisms linked to protein folding in Atlantic salmon smolt endoplasmic reticulum.
DOI: 10.6084/m9.figshare.3510011
title: Individual and molecular level effects of produced water contaminants on nauplii and adult females of <i>Calanus finmarchicus</i>

description: In the Barents Sea region new petroleum fields are discovered yearly and extraction of petroleum products is expected to increase in the upcoming years. Despite enhanced technology and stricter governmental legislation, establishment of the petroleum industry in the Barents Sea may potentially introduce a new source of contamination to the area, as some discharges of produced water will be allowed. Whether the presence of produced water poses a risk to the Arctic marine life remains to be investigated. The aim of this study was to examine effects of exposure to several compounds found in produced water—a mixture of selected organic compounds (APW), radium-226 (<sup>226</sup>Ra), barium (Ba), and a scale inhibitor—on the copepod species <i>Calanus finmarchicus</i>. Experiments were performed using exposure concentrations at realistic levels based on those detected in the vicinity of known discharge points. The influence of lethal and sublethal effects on early life stages was determined and significantly lower survival in the APW exposure groups was found. In the Ba treatment the life stage development did not proceed to the same advanced stages as observed in the control (filtered sea water). The scale inhibitor and <sup>226</sup>Ra treatments showed no significant difference from control. In addition, adult females were exposed to APW, <sup>226</sup>Ra, and a mixture of the two. Both individual-level effects (egg production and feeding) and molecular-level effects (gene expression) were assessed. On the individual level endpoints, only treatments including APW produced an effect compared to control. However, on the molecular level the possibility that also <sup>226</sup>Ra induced toxicologically relevant effects cannot be ruled out.
DOI: 10.6084/m9.figshare.3510011.v1
title: Individual and molecular level effects of produced water contaminants on nauplii and adult females of <i>Calanus finmarchicus</i>

description: In the Barents Sea region new petroleum fields are discovered yearly and extraction of petroleum products is expected to increase in the upcoming years. Despite enhanced technology and stricter governmental legislation, establishment of the petroleum industry in the Barents Sea may potentially introduce a new source of contamination to the area, as some discharges of produced water will be allowed. Whether the presence of produced water poses a risk to the Arctic marine life remains to be investigated. The aim of this study was to examine effects of exposure to several compounds found in produced water—a mixture of selected organic compounds (APW), radium-226 (<sup>226</sup>Ra), barium (Ba), and a scale inhibitor—on the copepod species <i>Calanus finmarchicus</i>. Experiments were performed using exposure concentrations at realistic levels based on those detected in the vicinity of known discharge points. The influence of lethal and sublethal effects on early life stages was determined and significantly lower survival in the APW exposure groups was found. In the Ba treatment the life stage development did not proceed to the same advanced stages as observed in the control (filtered sea water). The scale inhibitor and <sup>226</sup>Ra treatments showed no significant difference from control. In addition, adult females were exposed to APW, <sup>226</sup>Ra, and a mixture of the two. Both individual-level effects (egg production and feeding) and molecular-level effects (gene expression) were assessed. On the individual level endpoints, only treatments including APW produced an effect compared to control. However, on the molecular level the possibility that also <sup>226</sup>Ra induced toxicologically relevant effects cannot be ruled out.
DOI: 10.6084/m9.figshare.3510002
title: PPARγ non-covalent antagonists exhibit mutable binding modes with a similar free energy of binding: a case study

description: The structural and dynamical properties of PPARγ receptor in a complex with either partial or full agonists have been intensively studied but little is known about the receptor antagonistic conformation. A composition of microsecond accelerated molecular dynamics (aMD) simulation show that like partial agonists a non-covalent PPARγ full antagonist can bind in different modes of similar population size and free energies of binding. Four different and periodically exchanging ligand conformations are detected and described. The studied antagonist interacts with different receptor substructures and affects both the co-activator and the Cdk5 phosphorylation sites and, presumably, the natural complex with the DNA. However, no significant changes in the conformational states of the activation helix 12, and in particular an antagonist orientation, have been recorded. Finally, our results show also that the aMD approach can be successfully used in recovering the possible binding modes, considering fully the receptor flexibility, and is not dependent on the starting conformation.
DOI: 10.6084/m9.figshare.3510002.v1
title: PPARγ non-covalent antagonists exhibit mutable binding modes with a similar free energy of binding: a case study

description: The structural and dynamical properties of PPARγ receptor in a complex with either partial or full agonists have been intensively studied but little is known about the receptor antagonistic conformation. A composition of microsecond accelerated molecular dynamics (aMD) simulation show that like partial agonists a non-covalent PPARγ full antagonist can bind in different modes of similar population size and free energies of binding. Four different and periodically exchanging ligand conformations are detected and described. The studied antagonist interacts with different receptor substructures and affects both the co-activator and the Cdk5 phosphorylation sites and, presumably, the natural complex with the DNA. However, no significant changes in the conformational states of the activation helix 12, and in particular an antagonist orientation, have been recorded. Finally, our results show also that the aMD approach can be successfully used in recovering the possible binding modes, considering fully the receptor flexibility, and is not dependent on the starting conformation.
DOI: 10.6084/m9.figshare.3509999
title: Petrology and geochemistry of Early Cretaceous A-type granitoids and late Mesozoic mafic dikes and their relationship to adakitic intrusions in the lower Yangtze River belt, Southeast China

description: The relationship among magmatism, large-scale metallogenesis of Southeast China, and subduction of the Pacific plate has long been debated. The lower Yangtze River belt (LYRB) in the northeastern edge of Southeast China is characterized by intense late Mesozoic magmatism and associated polymetallic mineralization such as copper, gold, iron, tungsten, molybdenum, etc. The copper-related adakitic rocks (148–130 Ma) in this belt are the oldest episode of magmatism and intruded as small intermediate-acid intrusive bodies. The Huayuangong granitoids (HYG), located in the southern part of this belt, however, are copper-barren. Three granitoid samples from this pluton give zircon U–Pb ages of 126.4 ± 1.6 Ma, 125.9 ± 1.9 Ma, and 126.2 ± 1.2 Ma, respectively. The HYG has A-type affinity with metaluminous to weakly peraluminous, high FeO<sub>T</sub>/(FeO<sub>T</sub>+MgO) ratios, and high Zr+Nb+Ce+Yb contents. Meanwhile, 10 late Mesozoic mafic samples from the LYRB exhibit similar trace element characteristics to those of ‘continental arc andesite’ (CAA) and suggest an enriched lithospheric mantle source with depletion in high field strength elements (e.g. Nb, Ta, Zr, Hf, and Ti) and enrichment of large ion lithophile elements (e.g. Rb, Th, U, and Pb). Although the HYG exhibits similar Sr–Nd isotope composition with the mafic dikes, distinct whole-rock Pb isotope ratios imply that the granitoids and mafic magmas originated from heterogeneous mantle sources. Compared with coeval Baijuhuajian A-type rocks that are exposed along the Jiang–Shao fault of Southeast China, the HYG shows enriched Hf isotope ratios of zircon with <i>ε</i><sub>Hf</sub>(<i>t</i>) values ranging from −4.8 to −11.1. In the Yb/Ta <i>versus</i> Y/Nb diagram, being different from the major asthenospheric mantle-origin Baijuhuajian pluton, a large range of and high Y/Nb ratios as well as high Zr contents of the HYG pluton suggest a magmatic source of mixing between the asthenospheric and enriched crustal component in the LYRB. Compared with early-stage copper-related adakitic rocks (148–130 Ma) with subduction-related affinities and high oxygen fugacity, the copper-barren HYG has with-plate A-type affinities and lower oxygen fugacity. Summarizing, the production of early-stage (i.e. subduction related) adakitic rocks followed by late-stage A-type granitoids in the LYRB is ascribed to the rollback of the Palaeo-Pacific plate beneath Southeast China and associated with asthenospheric upwelling and lithospheric thinning during the late Mesozoic era.
DOI: 10.6084/m9.figshare.3509999.v1
title: Petrology and geochemistry of Early Cretaceous A-type granitoids and late Mesozoic mafic dikes and their relationship to adakitic intrusions in the lower Yangtze River belt, Southeast China

description: The relationship among magmatism, large-scale metallogenesis of Southeast China, and subduction of the Pacific plate has long been debated. The lower Yangtze River belt (LYRB) in the northeastern edge of Southeast China is characterized by intense late Mesozoic magmatism and associated polymetallic mineralization such as copper, gold, iron, tungsten, molybdenum, etc. The copper-related adakitic rocks (148–130 Ma) in this belt are the oldest episode of magmatism and intruded as small intermediate-acid intrusive bodies. The Huayuangong granitoids (HYG), located in the southern part of this belt, however, are copper-barren. Three granitoid samples from this pluton give zircon U–Pb ages of 126.4 ± 1.6 Ma, 125.9 ± 1.9 Ma, and 126.2 ± 1.2 Ma, respectively. The HYG has A-type affinity with metaluminous to weakly peraluminous, high FeO<sub>T</sub>/(FeO<sub>T</sub>+MgO) ratios, and high Zr+Nb+Ce+Yb contents. Meanwhile, 10 late Mesozoic mafic samples from the LYRB exhibit similar trace element characteristics to those of ‘continental arc andesite’ (CAA) and suggest an enriched lithospheric mantle source with depletion in high field strength elements (e.g. Nb, Ta, Zr, Hf, and Ti) and enrichment of large ion lithophile elements (e.g. Rb, Th, U, and Pb). Although the HYG exhibits similar Sr–Nd isotope composition with the mafic dikes, distinct whole-rock Pb isotope ratios imply that the granitoids and mafic magmas originated from heterogeneous mantle sources. Compared with coeval Baijuhuajian A-type rocks that are exposed along the Jiang–Shao fault of Southeast China, the HYG shows enriched Hf isotope ratios of zircon with <i>ε</i><sub>Hf</sub>(<i>t</i>) values ranging from −4.8 to −11.1. In the Yb/Ta <i>versus</i> Y/Nb diagram, being different from the major asthenospheric mantle-origin Baijuhuajian pluton, a large range of and high Y/Nb ratios as well as high Zr contents of the HYG pluton suggest a magmatic source of mixing between the asthenospheric and enriched crustal component in the LYRB. Compared with early-stage copper-related adakitic rocks (148–130 Ma) with subduction-related affinities and high oxygen fugacity, the copper-barren HYG has with-plate A-type affinities and lower oxygen fugacity. Summarizing, the production of early-stage (i.e. subduction related) adakitic rocks followed by late-stage A-type granitoids in the LYRB is ascribed to the rollback of the Palaeo-Pacific plate beneath Southeast China and associated with asthenospheric upwelling and lithospheric thinning during the late Mesozoic era.
DOI: 10.6084/m9.figshare.3509969
title: Circadian variation in clinical features and outcome of intracerebral hemorrhage: The INTERACT studies

description: Previous studies consistently reported a diurnal variation in the occurrence of intracerebral hemorrhage (ICH), with a morning peak. However, limited knowledge exists on the circadian pattern of ICH severity and outcome. This study aimed to determine possible associations between ICH onset time and admission severity and 90-day outcomes using the combined data set of the pilot and main-phase Intensive blood pressure (BP) reduction in an acute cerebral hemorrhage trial (INTERACT). The ICH onset time was categorized into three groups (1: 00:00–07:59; 2: 08:00–15:59; and 3: 16:00–23:59). We found an association between onset time and low Glasgow Coma Scale score: aOR (time 1: 1.72, 95% CI 1.12–2.66; time 3: 1.95, 95% CI 1.31–2.89, <i>p</i> = 0.003; in comparison to time 2). There was no association between onset time and volume of ICH (adjusted <i>p</i> = 0.354) or 90-day outcomes of death or major disability, and death and major disability separately (all adjusted <i>p</i> &gt; 0.4). The results showed that more severe cases of ICH patients, defined by a reduced level of consciousness, had late afternoon to early morning stroke onset, but this was unrelated to baseline hematoma volume or location. There was no circadian influence on ICH clinical outcome.