cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.5281/zenodo.15213423
title: Supporting data for Quantifying Equilibrium Climate Sensitivity to Atmosphere Chemistry and Composition Representations in GFDL-CM4.0 and GFDL-ESM4.1.

description: This repository contains the model source code, input files, output files, and analysis scripts from GFDL-CM4-SOM and GFDL-ESM4-SOM slab ocean model simulations used in the analyses presented in "Quantifying Equilibrium Climate Sensitivity to Atmospheric Chemistry and Composition Representations in GFDL-CM4.0 and GFDL-ESM4.1", submitted to Geophysical Research Letters.
DOI: 10.5281/zenodo.15213424
title: Supporting data for Quantifying Equilibrium Climate Sensitivity to Atmosphere Chemistry and Composition Representations in GFDL-CM4.0 and GFDL-ESM4.1.

description: This repository contains the model source code, input files, output files, and analysis scripts from GFDL-CM4-SOM and GFDL-ESM4-SOM slab ocean model simulations used in the analyses presented in "Quantifying Equilibrium Climate Sensitivity to Atmospheric Chemistry and Composition Representations in GFDL-CM4.0 and GFDL-ESM4.1", submitted to Geophysical Research Letters.
DOI: 10.5281/zenodo.15221438
title: Supporting data for Quantifying Equilibrium Climate Sensitivity to Atmosphere Chemistry and Composition Representations in GFDL-CM4.0 and GFDL-ESM4.1.

description: This repository contains the model source code, input files, output files, and analysis scripts from GFDL-CM4-SOM and GFDL-ESM4-SOM slab ocean model simulations used in the analyses presented in "Quantifying Equilibrium Climate Sensitivity to Atmospheric Chemistry and Composition Representations in GFDL-CM4.0 and GFDL-ESM4.1", submitted to Geophysical Research Letters.
DOI: 10.5281/zenodo.15221510
title: Supporting data for Quantifying Equilibrium Climate Sensitivity to Atmosphere Chemistry and Composition Representations in GFDL-CM4.0 and GFDL-ESM4.1.

description: This repository contains the model source code, input files, output files, and analysis scripts from GFDL-CM4-SOM and GFDL-ESM4-SOM slab ocean model simulations used in the analyses presented in "Quantifying Equilibrium Climate Sensitivity to Atmospheric Chemistry and Composition Representations in GFDL-CM4.0 and GFDL-ESM4.1", submitted to Geophysical Research Letters.
DOI: 10.15468/dl.ze9ecq
title: Occurrence Download

description: A dataset containing 553793 species occurrences available in GBIF matching the query:
{
 "and" : [
 "Geometry POLYGON((92.89062 28.46217,94.30534 26.308,95.90331 27.15252,96.34311 28.62315,95.52214 29.63482,92.89062 28.46217))",
 "HasCoordinate is true",
 "HasGeospatialIssue is false",
 "OccurrenceStatus is Present"
 ]
}

 The dataset includes 553793 records from 270 constituent datasets; see https://api.gbif.org/v1/occurrence/download/0022867-250402121839773/datasets/export for details.
 
Data from some individual datasets included in this download may be licensed under less restrictive terms.
DOI: 10.6084/m9.figshare.11948820
title: Sulforaphane Activates a lysosome-dependent transcriptional program to mitigate oxidative stress

description: Oxidative stress underlies a number of pathological conditions, including cancer, neurodegeneration, and aging. Antioxidant-rich foods help maintain cellular redox homeostasis and mitigate oxidative stress, but the underlying mechanisms are not clear. For example, sulforaphane (SFN), an electrophilic compound that is enriched in cruciferous vegetables such as broccoli, is a potent inducer of cellular antioxidant responses. NFE2L2/NRF2 (nuclear factor, erythroid 2 like 2), a transcriptional factor that controls the expression of multiple detoxifying enzymes through antioxidant response elements (AREs), is a proposed target of SFN. <i>NFE2L2/NRF2</i> is a target gene of TFEB (transcription factor EB), a master regulator of autophagic and lysosomal functions, which we show here to be potently activated by SFN. SFN induces TFEB nuclear translocation via a Ca<sup>2+</sup>-dependent but MTOR (mechanistic target of rapamycin kinase)-independent mechanism through a moderate increase in reactive oxygen species (ROS). Activated TFEB then boosts the expression of genes required for autophagosome and lysosome biogenesis, which are known to facilitate the clearance of damaged mitochondria. Notably, TFEB activity is required for SFN-induced protection against both acute oxidant bursts and chronic oxidative stress. Hence, by simultaneously activating macroautophagy/autophagy and detoxifying pathways, natural compound SFN may trigger a self-defense cellular mechanism that can effectively mitigate oxidative stress commonly associated with many metabolic and age-related diseases. <b>Abbreviations:</b> ANOVA: analyzes of variance; AREs: antioxidant response elements; Baf-A1: bafilomycin A<sub>1</sub>; BHA: butylhydroxyanisole; CAT: catechin hydrate; CCCP: carbonyl cyanide m- chlorophenylhydrazone; CLEAR: coordinated lysosomal expression and regulation; DCFH-DA: 2ʹ,7ʹ-dichlorofluorescin diacetate; FBS: fetal bovine serum; GFP: green fluorescent protein; HMOX1/HO-1: heme oxygenase 1; KD: knockdown; KEAP1: kelch like ECH associated protein 1; KO: knockout; LAMP1: lysosomal associated membrane protein 1; MCOLN1/TRPML1: mucolipin 1; ML-SA1: mucolipin-specific synthetic agonist 1; ML-SI3: mucolipin-specific synthetic inhibitor 3; MTOR: mechanistic target of rapamycin kinase; MTORC1: mechanistic target of rapamycin kinase complex 1; NAC: N-acetylcysteine; NFE2L2/NRF2: nuclear factor: erythroid 2 like 2; NPC: Niemann–Pick type C; PBS: phosphate-buffered saline; PPP2/PP2A: protein phosphatase 2; Q-PCR: real time polymerase chain reaction; ROS: reactive oxygen species; RPS6KB1/S6K1/p70S6K: ribosomal protein S6 kinase B1; SFN: sulforaphane; TFEB: transcription factor EB; WT, wild-type
DOI: 10.6084/m9.figshare.11948820.v4
title: Sulforaphane Activates a lysosome-dependent transcriptional program to mitigate oxidative stress

description: Oxidative stress underlies a number of pathological conditions, including cancer, neurodegeneration, and aging. Antioxidant-rich foods help maintain cellular redox homeostasis and mitigate oxidative stress, but the underlying mechanisms are not clear. For example, sulforaphane (SFN), an electrophilic compound that is enriched in cruciferous vegetables such as broccoli, is a potent inducer of cellular antioxidant responses. NFE2L2/NRF2 (nuclear factor, erythroid 2 like 2), a transcriptional factor that controls the expression of multiple detoxifying enzymes through antioxidant response elements (AREs), is a proposed target of SFN. <i>NFE2L2/NRF2</i> is a target gene of TFEB (transcription factor EB), a master regulator of autophagic and lysosomal functions, which we show here to be potently activated by SFN. SFN induces TFEB nuclear translocation via a Ca<sup>2+</sup>-dependent but MTOR (mechanistic target of rapamycin kinase)-independent mechanism through a moderate increase in reactive oxygen species (ROS). Activated TFEB then boosts the expression of genes required for autophagosome and lysosome biogenesis, which are known to facilitate the clearance of damaged mitochondria. Notably, TFEB activity is required for SFN-induced protection against both acute oxidant bursts and chronic oxidative stress. Hence, by simultaneously activating macroautophagy/autophagy and detoxifying pathways, natural compound SFN may trigger a self-defense cellular mechanism that can effectively mitigate oxidative stress commonly associated with many metabolic and age-related diseases. <b>Abbreviations:</b> ANOVA: analyzes of variance; AREs: antioxidant response elements; Baf-A1: bafilomycin A<sub>1</sub>; BHA: butylhydroxyanisole; CAT: catechin hydrate; CCCP: carbonyl cyanide m- chlorophenylhydrazone; CLEAR: coordinated lysosomal expression and regulation; DCFH-DA: 2ʹ,7ʹ-dichlorofluorescin diacetate; FBS: fetal bovine serum; GFP: green fluorescent protein; HMOX1/HO-1: heme oxygenase 1; KD: knockdown; KEAP1: kelch like ECH associated protein 1; KO: knockout; LAMP1: lysosomal associated membrane protein 1; MCOLN1/TRPML1: mucolipin 1; ML-SA1: mucolipin-specific synthetic agonist 1; ML-SI3: mucolipin-specific synthetic inhibitor 3; MTOR: mechanistic target of rapamycin kinase; MTORC1: mechanistic target of rapamycin kinase complex 1; NAC: N-acetylcysteine; NFE2L2/NRF2: nuclear factor: erythroid 2 like 2; NPC: Niemann–Pick type C; PBS: phosphate-buffered saline; PPP2/PP2A: protein phosphatase 2; Q-PCR: real time polymerase chain reaction; ROS: reactive oxygen species; RPS6KB1/S6K1/p70S6K: ribosomal protein S6 kinase B1; SFN: sulforaphane; TFEB: transcription factor EB; WT, wild-type
DOI: 10.6084/m9.figshare.11948820.v3
title: Sulforaphane Activates a lysosome-dependent transcriptional program to mitigate oxidative stress

description: Oxidative stress underlies a number of pathological conditions, including cancer, neurodegeneration, and aging. Antioxidant-rich foods help maintain cellular redox homeostasis and mitigate oxidative stress, but the underlying mechanisms are not clear. For example, sulforaphane (SFN), an electrophilic compound that is enriched in cruciferous vegetables such as broccoli, is a potent inducer of cellular antioxidant responses. NFE2L2/NRF2 (nuclear factor, erythroid 2 like 2), a transcriptional factor that controls the expression of multiple detoxifying enzymes through antioxidant response elements (AREs), is a proposed target of SFN. <i>NFE2L2/NRF2</i> is a target gene of TFEB (transcription factor EB), a master regulator of autophagic and lysosomal functions, which we show here to be potently activated by SFN. SFN induces TFEB nuclear translocation via a Ca<sup>2+</sup>-dependent but MTOR (mechanistic target of rapamycin kinase)-independent mechanism through a moderate increase in reactive oxygen species (ROS). Activated TFEB then boosts the expression of genes required for autophagosome and lysosome biogenesis, which are known to facilitate the clearance of damaged mitochondria. Notably, TFEB activity is required for SFN-induced protection against both acute oxidant bursts and chronic oxidative stress. Hence, by simultaneously activating macroautophagy/autophagy and detoxifying pathways, natural compound SFN may trigger a self-defense cellular mechanism that can effectively mitigate oxidative stress commonly associated with many metabolic and age-related diseases. <b>Abbreviations:</b> ANOVA: analyzes of variance; AREs: antioxidant response elements; Baf-A1: bafilomycin A<sub>1</sub>; BHA: butylhydroxyanisole; CAT: catechin hydrate; CCCP: carbonyl cyanide m- chlorophenylhydrazone; CLEAR: coordinated lysosomal expression and regulation; DCFH-DA: 2ʹ,7ʹ-dichlorofluorescin diacetate; FBS: fetal bovine serum; GFP: green fluorescent protein; HMOX1/HO-1: heme oxygenase 1; KD: knockdown; KEAP1: kelch like ECH associated protein 1; KO: knockout; LAMP1: lysosomal associated membrane protein 1; MCOLN1/TRPML1: mucolipin 1; ML-SA1: mucolipin-specific synthetic agonist 1; ML-SI3: mucolipin-specific synthetic inhibitor 3; MTOR: mechanistic target of rapamycin kinase; MTORC1: mechanistic target of rapamycin kinase complex 1; NAC: N-acetylcysteine; NFE2L2/NRF2: nuclear factor: erythroid 2 like 2; NPC: Niemann–Pick type C; PBS: phosphate-buffered saline; PPP2/PP2A: protein phosphatase 2; Q-PCR: real time polymerase chain reaction; ROS: reactive oxygen species; RPS6KB1/S6K1/p70S6K: ribosomal protein S6 kinase B1; SFN: sulforaphane; TFEB: transcription factor EB; WT, wild-type
DOI: 10.6084/m9.figshare.11919777.v2
title: Oncogenic role of <i>MIR516A</i> in human bladder cancer was mediated by its attenuating PHLPP2 expression and BECN1-dependent autophagy

description: Although <i>MIR516A</i> has been reported to be downregulated and act as a tumor suppressor in multiple cancers, its expression and potential contribution to human bladder cancer (BC) remain unexplored. Unexpectedly, we showed here that <i>MIR516A</i> was markedly upregulated in human BC tissues and cell lines, while inhibition of <i>MIR516A</i> expression attenuated BC cell monolayer growth <i>in vitro</i> and xenograft tumor growth <i>in vivo</i>, accompanied with increased expression of PHLPP2. Further studies showed that <i>MIR516A</i> was able to directly bind to the 3′-untranslated region of <i>PHLPP2</i> mRNA, which was essential for its attenuating PHLPP2 expression. The knockdown of <i>PHLPP2</i> expression in <i>MIR516A</i>-inhibited cells could reverse BC cell growth, suggesting that PHLPP2 is a <i>MIR516A</i> downstream mediator responsible for <i>MIR516A</i> oncogenic effect. PHLPP2 was able to mediate BECN1/Beclin1 stabilization indirectly, therefore promoting BECN1-dependent macroautophagy/autophagy, and inhibiting BC tumor cell growth. In addition, our results indicated that the increased autophagy by attenuating <i>MIR516A</i> resulted in a dramatic inhibition of xenograft tumor formation <i>in vivo</i>. Collectively, our results reveal that <i>MIR516A</i> has a novel oncogenic function in BC growth by directing binding to <i>PHLPP2</i> 3′-UTR and inhibiting PHLPP2 expression, in turn at least partly promoting CUL4A-mediated BECN1 protein degradation, thereby attenuating autophagy and promoting BC growth, which is a distinct function of <i>MIR516A</i> identified in other cancers. <b>Abbreviation:</b> ATG3: autophagy related 3; ATG5: autophagy related 5; ATG7: autophagy related 7; ATG12: autophagy related 12; BAF: bafilomycin A<sub>1</sub>; BC: bladder cancer; CHX: cycloheximide; Co-IP: co-immunoprecipitation; CUL3: cullin 3; CUL4A: cullin 4A; CUL4B: cullin 4B; IF: immunofluorescence: IHC-p: immunohistochemistry-paraffin; <i>MIR516A</i>: microRNA 516a (microRNA 516a1 and microRNA 516a2); MS: mass spectrometry; PHLPP2: PH domain and leucine rich repeat protein phosphatase.
DOI: 10.6084/m9.figshare.11987310
title: The autophagic response to <i>Staphylococcus aureus</i> provides an intracellular niche in neutrophils

description: <i>Staphylococcus aureus</i> is a major human pathogen causing multiple pathologies, from cutaneous lesions to life-threatening sepsis. Although neutrophils contribute to immunity against <i>S. aureus</i>, multiple lines of evidence suggest that these phagocytes can provide an intracellular niche for staphylococcal dissemination. However, the mechanism of neutrophil subversion by intracellular <i>S. aureus</i> remains unknown. Targeting of intracellular pathogens by macroautophagy/autophagy is recognized as an important component of host innate immunity, but whether autophagy is beneficial or detrimental to <i>S. aureus</i>-infected hosts remains controversial. Here, using larval zebrafish, we showed that the autophagy marker Lc3 rapidly decorates <i>S. aureus</i> following engulfment by macrophages and neutrophils. Upon phagocytosis by neutrophils, Lc3-positive, non-acidified spacious phagosomes are formed. This response is dependent on phagocyte NADPH oxidase as both <i>cyba/p22phox</i> knockdown and diphenyleneiodonium (DPI) treatment inhibited Lc3 decoration of phagosomes. Importantly, NADPH oxidase inhibition diverted neutrophil <i>S. aureus</i> processing into tight acidified vesicles, which resulted in increased host resistance to the infection. Some intracellular bacteria within neutrophils were also tagged by Sqstm1/p62-GFP fusion protein and loss of Sqstm1 impaired host defense. Together, we have shown that intracellular handling of <i>S. aureus</i> by neutrophils is best explained by Lc3-associated phagocytosis (LAP), which appears to provide an intracellular niche for bacterial pathogenesis, while the selective autophagy receptor Sqstm1 is host-protective. The antagonistic roles of LAP and Sqstm1-mediated pathways in <i>S. aureus</i>-infected neutrophils may explain the conflicting reports relating to anti-staphylococcal autophagy and provide new insights for therapeutic strategies against antimicrobial-resistant <i>Staphylococci</i>. <b>Abbreviations:</b> ATG: autophagy related; CFU: colony-forming units; CMV: cytomegalovirus; Cyba/P22phox: cytochrome b-245, alpha polypeptide; DMSO: dimethyl sulfoxide; DPI: diphenyleneiodonium; EGFP: enhanced green fluorescent protein; GFP: green fluorescent protein; hpf: hours post-fertilization; hpi: hours post-infection; Irf8: interferon regulatory factor 8; LAP: LC3-associated phagocytosis; lyz: lysozyme; LWT: london wild type; Map1lc3/Lc3: microtubule-associated protein 1 light chain 3; NADPH oxidase: nicotinamide adenine dinucleotide phosphate oxidase; RFP: red fluorescent protein; ROS: reactive oxygen species; RT-PCR: reverse transcriptase polymerase chain reaction; Sqstm1/p62: sequestosome 1; Tg: transgenic; TSA: tyramide signal amplification.
DOI: 10.6084/m9.figshare.11987310.v3
title: The autophagic response to <i>Staphylococcus aureus</i> provides an intracellular niche in neutrophils

description: <i>Staphylococcus aureus</i> is a major human pathogen causing multiple pathologies, from cutaneous lesions to life-threatening sepsis. Although neutrophils contribute to immunity against <i>S. aureus</i>, multiple lines of evidence suggest that these phagocytes can provide an intracellular niche for staphylococcal dissemination. However, the mechanism of neutrophil subversion by intracellular <i>S. aureus</i> remains unknown. Targeting of intracellular pathogens by macroautophagy/autophagy is recognized as an important component of host innate immunity, but whether autophagy is beneficial or detrimental to <i>S. aureus</i>-infected hosts remains controversial. Here, using larval zebrafish, we showed that the autophagy marker Lc3 rapidly decorates <i>S. aureus</i> following engulfment by macrophages and neutrophils. Upon phagocytosis by neutrophils, Lc3-positive, non-acidified spacious phagosomes are formed. This response is dependent on phagocyte NADPH oxidase as both <i>cyba/p22phox</i> knockdown and diphenyleneiodonium (DPI) treatment inhibited Lc3 decoration of phagosomes. Importantly, NADPH oxidase inhibition diverted neutrophil <i>S. aureus</i> processing into tight acidified vesicles, which resulted in increased host resistance to the infection. Some intracellular bacteria within neutrophils were also tagged by Sqstm1/p62-GFP fusion protein and loss of Sqstm1 impaired host defense. Together, we have shown that intracellular handling of <i>S. aureus</i> by neutrophils is best explained by Lc3-associated phagocytosis (LAP), which appears to provide an intracellular niche for bacterial pathogenesis, while the selective autophagy receptor Sqstm1 is host-protective. The antagonistic roles of LAP and Sqstm1-mediated pathways in <i>S. aureus</i>-infected neutrophils may explain the conflicting reports relating to anti-staphylococcal autophagy and provide new insights for therapeutic strategies against antimicrobial-resistant <i>Staphylococci</i>. <b>Abbreviations:</b> ATG: autophagy related; CFU: colony-forming units; CMV: cytomegalovirus; Cyba/P22phox: cytochrome b-245, alpha polypeptide; DMSO: dimethyl sulfoxide; DPI: diphenyleneiodonium; EGFP: enhanced green fluorescent protein; GFP: green fluorescent protein; hpf: hours post-fertilization; hpi: hours post-infection; Irf8: interferon regulatory factor 8; LAP: LC3-associated phagocytosis; lyz: lysozyme; LWT: london wild type; Map1lc3/Lc3: microtubule-associated protein 1 light chain 3; NADPH oxidase: nicotinamide adenine dinucleotide phosphate oxidase; RFP: red fluorescent protein; ROS: reactive oxygen species; RT-PCR: reverse transcriptase polymerase chain reaction; Sqstm1/p62: sequestosome 1; Tg: transgenic; TSA: tyramide signal amplification.
DOI: 10.15468/dl.yce9e8
title: Occurrence Download

description: A dataset containing 40 species occurrences available in GBIF matching the query:
{
 "and" : [
 "SpeciesKey is one of (Pipiza bimaculata Meigen, 1822)",
 "BasisOfRecord is one of (Human Observation, Observation, Occurrence evidence)",
 "Year is greater than or equal to 1901",
 "Year is less than or equal to 2019",
 "HasCoordinate is true",
 "HasGeospatialIssue is false",
 "OccurrenceStatus is Present"
 ]
}

 The dataset includes 40 records from 12 constituent datasets; see https://api.gbif.org/v1/occurrence/download/0017656-240906103802322/datasets/export for details.
 
Data from some individual datasets included in this download may be licensed under less restrictive terms.
DOI: 10.6084/m9.figshare.12123720
title: A monolayer hiPSC culture system for autophagy/mitophagy studies in human dopaminergic neurons

description: Macroautophagy/autophagy cytoplasmic quality control pathways are required during neural development and are critical for the maintenance of functional neuronal populations in the adult brain. Robust evidence now exists that declining neuronal autophagy pathways contribute to human neurodegenerative diseases, including Parkinson disease (PD). Reliable and relevant human neuronal model systems are therefore needed to understand the biology of disease-vulnerable neural populations, to decipher the underlying causes of neurodegenerative disease, and to develop assays to test therapeutic interventions <i>in vitro</i>. Human induced pluripotent stem cell (hiPSC) neural model systems can meet this demand: they provide a renewable source of material for differentiation into regional neuronal sub-types for functional assays; they can be expanded to provide a platform for screening, and they can potentially be optimized for transplantation/neurorestorative therapy. So far, however, hiPSC differentiation protocols for the generation of ventral midbrain dopaminergic neurons (mDANs) – the predominant neuronal sub-type afflicted in PD – have been somewhat restricted by poor efficiency and/or suitability for functional and/or imaging-based <i>in vitro</i> assays. Here, we describe a reliable, monolayer differentiation protocol for the rapid and reproducible production of high numbers of mDANs from hiPSC in a format that is amenable for autophagy/mitophagy research. We characterize these cells with respect to neuronal differentiation and macroautophagy capability and describe qualitative and quantitative assays for the study of autophagy and mitophagy in these important cells. <b>Abbreviations:</b> AA: ascorbic acid; ATG: autophagy-related; BDNF: brain derived neurotrophic factor; CCCP: carbonyl cyanide m-chlorophenylhydrazone; dbcAMP: dibutyryl cAMP; DAN: dopaminergic neuron; DAPI: 4ʹ,6-diamidino-2-phenylindole; DAPT: N-[N-(3,5-difluorophenacetyl)-L-alanyl]-sphenylglycine; DLG4/PSD95: discs large MAGUK scaffold protein 4; DMEM: Dulbecco’s modified eagle’s medium; EB: embryoid body; ECAR: extracellular acidification rate; EGF: epidermal growth factor; FACS: fluorescence-activated cell sorting; FCCP: arbonyl cyanide p-triflouromethoxyphenylhydrazone; FGF: fibroblast growth factor; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GDNF: glia cell derived neurotrophic factor; hiPSC: human induced pluripotent stem cell; LAMP2A: lysosomal associated membrane protein 2A; LT-R: LysoTracker Red; MAP1LC3: microtubule associated protein 1 light chain 3; mDAN: midbrain dopaminergic neuron; MEF: mouse embryonic fibroblast; MT-GR: MitoTracker Green; MT-R: MitoTracker Red; NAS2: normal SNCA2; NEM: neuroprogenitor expansion media; NR4A2/NURR1: nuclear receptor subfamily group A member 2; OA: oligomycin and antimycin A; OCR: oxygen consumption rate; PD: Parkinson disease; SHH: sonic hedgehog signaling molecule; SNCA/α-synuclein: synuclein alpha; TH: tyrosine hydroxylase; VTN: vitronectin.