cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.25582/data.2024-02.3034724/2548717
title: Data for EMSL Project 60579 from February 2024
DOI: 10.25582/data.2024-02.3034725/2548718
title: Data for EMSL Project 60579 from February 2024
DOI: 10.25582/data.2024-02.3034726/2548719
title: Data for EMSL Project 60579 from February 2024
DOI: 10.25582/data.2024-02.3034727/2548720
title: Data for EMSL Project 60579 from February 2024
DOI: 10.25582/data.2024-02.3034728/2548721
title: Data for EMSL Project 60579 from February 2024
DOI: 10.6084/m9.figshare.30039682
title: UCHL1 alleviates nucleus pulposus cell senescence by promoting chaperone-mediated autophagy antagonizing autophagy-dependent ferroptosis through deubiquitination of HSPA8

description: Chaperone-mediated autophagy (CMA), a lysosome-dependent protein degradation pathway, plays a pivotal yet poorly understood role in cellular senescence-related degenerative diseases. Our study sheds light on a novel mechanism whereby UCHL1 plays a crucial role in mitigating nucleus pulposus cell (NPC) senescence and intervertebral disc degeneration (IVDD) by activating CMA to counteract autophagy-dependent ferroptosis. Through sequencing analysis of human samples, we identified UCHL1 as a potential factor influencing disc degeneration. Further research revealed that UCHL1 activates CMA by stabilizing HSPA8 through deubiquitination. HSPA8, in turn, recognizes and promotes the degradation of HPCAL1 via the CMA pathway by binding to its “KFERQ” motif, ultimately alleviating NPC senescence. Importantly, we demonstrated that engineered exosomes delivering <i>UCHL1</i>-overexpressing plasmids effectively alleviated NPC senescence and significantly mitigated the progression of IVDD. This finding underscores the significance of CMA-regulated ferroptosis in IVDD through UCHL1 modulation and as a promising target for improving chronic pain and IVDD progression. <b>Abbreviations:</b> AAV: adeno-associated virus; AB: Alcian Blue; ACSL4: acyl-CoA synthetase long chain family member 4; ALP: autophagy-lysosome pathway; Baf-A1: bafilomycin A1; CHX: cycloheximide; CMA: chaperone-mediated autophagy; Co-IP: co-immunoprecipitation; DUBs: deubiquitinating enzymes; eMI: endosomal microautophagy; Evs: extracellular vesicles; Exo: exosome; GPX4: glutathione peroxidase 4; H&E: hematoxylin and eosin; HsNPCs: Human NPCs; IF: immunofluorescence; IHC: immunohistochemistry; IP-MS: immunoprecipitation mass spectrometry; IVDD: intervertebral disc degeneration; IVDs: intervertebral discs; LBP: low back pain; LDP: lumbar disc prolapse; MRI: magnetic resonance imaging; N/L: NH4Cl and leupeptin; NP: nucleus pulposus; NPCs: nucleus pulposus cells; PCA: principal component analysis; qRT-PCR: quantitative real-time PCR; RnBMSCs: rat bone marrow mesenchymal stem cells; RnNPCs: rat NPCs; ROS: reactive oxygen species; SA-GLB1/β-gal: senescence-associated galactosidase beta 1; SASP: senescence-associated secretory phenotype; SD: Sprague-Dawley; SO: Safranin O-Fast Green; TBHP: tert-butyl hydroperoxide; UCHL1: ubiquitin C-terminal hydrolase L1; UPS: ubiquitin-proteasome system
DOI: 10.6084/m9.figshare.30039682.v1
title: UCHL1 alleviates nucleus pulposus cell senescence by promoting chaperone-mediated autophagy antagonizing autophagy-dependent ferroptosis through deubiquitination of HSPA8

description: Chaperone-mediated autophagy (CMA), a lysosome-dependent protein degradation pathway, plays a pivotal yet poorly understood role in cellular senescence-related degenerative diseases. Our study sheds light on a novel mechanism whereby UCHL1 plays a crucial role in mitigating nucleus pulposus cell (NPC) senescence and intervertebral disc degeneration (IVDD) by activating CMA to counteract autophagy-dependent ferroptosis. Through sequencing analysis of human samples, we identified UCHL1 as a potential factor influencing disc degeneration. Further research revealed that UCHL1 activates CMA by stabilizing HSPA8 through deubiquitination. HSPA8, in turn, recognizes and promotes the degradation of HPCAL1 via the CMA pathway by binding to its “KFERQ” motif, ultimately alleviating NPC senescence. Importantly, we demonstrated that engineered exosomes delivering <i>UCHL1</i>-overexpressing plasmids effectively alleviated NPC senescence and significantly mitigated the progression of IVDD. This finding underscores the significance of CMA-regulated ferroptosis in IVDD through UCHL1 modulation and as a promising target for improving chronic pain and IVDD progression. <b>Abbreviations:</b> AAV: adeno-associated virus; AB: Alcian Blue; ACSL4: acyl-CoA synthetase long chain family member 4; ALP: autophagy-lysosome pathway; Baf-A1: bafilomycin A1; CHX: cycloheximide; CMA: chaperone-mediated autophagy; Co-IP: co-immunoprecipitation; DUBs: deubiquitinating enzymes; eMI: endosomal microautophagy; Evs: extracellular vesicles; Exo: exosome; GPX4: glutathione peroxidase 4; H&E: hematoxylin and eosin; HsNPCs: Human NPCs; IF: immunofluorescence; IHC: immunohistochemistry; IP-MS: immunoprecipitation mass spectrometry; IVDD: intervertebral disc degeneration; IVDs: intervertebral discs; LBP: low back pain; LDP: lumbar disc prolapse; MRI: magnetic resonance imaging; N/L: NH4Cl and leupeptin; NP: nucleus pulposus; NPCs: nucleus pulposus cells; PCA: principal component analysis; qRT-PCR: quantitative real-time PCR; RnBMSCs: rat bone marrow mesenchymal stem cells; RnNPCs: rat NPCs; ROS: reactive oxygen species; SA-GLB1/β-gal: senescence-associated galactosidase beta 1; SASP: senescence-associated secretory phenotype; SD: Sprague-Dawley; SO: Safranin O-Fast Green; TBHP: tert-butyl hydroperoxide; UCHL1: ubiquitin C-terminal hydrolase L1; UPS: ubiquitin-proteasome system
DOI: 10.6084/m9.figshare.29977668
title: A novel <i>C. elegans</i> model for MAPT/Tau spreading reveals genes critical for endolysosomal integrity and seeded MAPT/Tau aggregation

description: The spreading of MAPT/Tau pathology is closely associated with the progression of neurodegeneration and cognitive decline in Alzheimer disease and other tauopathies. A key event in this process is the rupture of endolysosomal vesicles following the intercellular transfer of MAPT/Tau aggregates, releasing the transferred MAPT/Tau species into the cytosol where they can promote the aggregation of endogenous MAPT/Tau. However, understanding of the cellular pathways involved in this process remains limited. In this study, we investigated cellular pathways that prevent endolysosomal vesicle rupture. We established a new <i>C. elegans</i> model of MAPT/Tau spreading by introducing an mCherry-labeled, disease-associated aggregation-prone fragment of human MAPT/Tau (F3ΔK281::mCh) into the six touch receptor neurons. F3ΔK281::mCh transgenic animals exhibited significant neurotoxicity and mechanosensory deficits due to the accumulation of this MAPT/Tau fragment. In addition, its intercellular transmission compromised the endolysosomal system in receiving hypodermal cells. Using this model, we conducted an unbiased genome-wide RNAi screen and identified 59 genes critical for maintaining endolysosomal integrity. GO-term analysis revealed an enrichment of genes related to the ESCRT complex, the ubiquitin-proteasome system, mRNA splicing, and fatty acid metabolism. Silencing of selected conserved genes exacerbated seeded MAPT/Tau aggregation in a human induced pluripotent stem cell (hiPSC)-derived cortical neuron model and triggered endolysosomal rupture in HEK293T cells, confirming the crucial role of endolysosomal damage in seeded MAPT/Tau aggregation. Overall, this study discovered novel cellular pathways that safeguard endolysosomal integrity. These findings may guide the development of therapeutics that improve endolysosomal integrity to halt the progression of MAPT/Tau pathology. <b>Abbreviations</b>: AD: Alzheimer disease; ALM: anterior lateral microtubule cell; AVM: anterior ventral microtubule cell; BWM: body wall muscle; <i>C. elegans</i>: <i>Caenorhabditis elegans</i>; DA: dopaminergic; hiPSC: human induced pluripotent stem cell; LGALS3: galectin 3; MAPT/Tau: microtubule associated protein tau; mCh: monomeric Cherry; PD: Parkinson disease; PLM: posterior lateral microtubule cell; PVM: posterior ventral microtubule cell; sfGFP: superfolder green flourescent protein; SNCA: synuclein alpha; nt-cntrl: non-targeting siRNA; rPHFs: recombinant paired helical filaments
DOI: 10.6084/m9.figshare.29977668.v1
title: A novel <i>C. elegans</i> model for MAPT/Tau spreading reveals genes critical for endolysosomal integrity and seeded MAPT/Tau aggregation

description: The spreading of MAPT/Tau pathology is closely associated with the progression of neurodegeneration and cognitive decline in Alzheimer disease and other tauopathies. A key event in this process is the rupture of endolysosomal vesicles following the intercellular transfer of MAPT/Tau aggregates, releasing the transferred MAPT/Tau species into the cytosol where they can promote the aggregation of endogenous MAPT/Tau. However, understanding of the cellular pathways involved in this process remains limited. In this study, we investigated cellular pathways that prevent endolysosomal vesicle rupture. We established a new <i>C. elegans</i> model of MAPT/Tau spreading by introducing an mCherry-labeled, disease-associated aggregation-prone fragment of human MAPT/Tau (F3ΔK281::mCh) into the six touch receptor neurons. F3ΔK281::mCh transgenic animals exhibited significant neurotoxicity and mechanosensory deficits due to the accumulation of this MAPT/Tau fragment. In addition, its intercellular transmission compromised the endolysosomal system in receiving hypodermal cells. Using this model, we conducted an unbiased genome-wide RNAi screen and identified 59 genes critical for maintaining endolysosomal integrity. GO-term analysis revealed an enrichment of genes related to the ESCRT complex, the ubiquitin-proteasome system, mRNA splicing, and fatty acid metabolism. Silencing of selected conserved genes exacerbated seeded MAPT/Tau aggregation in a human induced pluripotent stem cell (hiPSC)-derived cortical neuron model and triggered endolysosomal rupture in HEK293T cells, confirming the crucial role of endolysosomal damage in seeded MAPT/Tau aggregation. Overall, this study discovered novel cellular pathways that safeguard endolysosomal integrity. These findings may guide the development of therapeutics that improve endolysosomal integrity to halt the progression of MAPT/Tau pathology. <b>Abbreviations</b>: AD: Alzheimer disease; ALM: anterior lateral microtubule cell; AVM: anterior ventral microtubule cell; BWM: body wall muscle; <i>C. elegans</i>: <i>Caenorhabditis elegans</i>; DA: dopaminergic; hiPSC: human induced pluripotent stem cell; LGALS3: galectin 3; MAPT/Tau: microtubule associated protein tau; mCh: monomeric Cherry; PD: Parkinson disease; PLM: posterior lateral microtubule cell; PVM: posterior ventral microtubule cell; sfGFP: superfolder green flourescent protein; SNCA: synuclein alpha; nt-cntrl: non-targeting siRNA; rPHFs: recombinant paired helical filaments
DOI: 10.6084/m9.figshare.29999871
title: Impaired MAPT/tau-secretory lysosomes are linked to cognitive vulnerability in Alzheimer patients

description: MAPT/tau proteins propagate between brain regions in a prion-like manner, driving the onset and progression of dementia in Alzheimer disease (AD). However, the basis for variability in dementia progression among AD patients remains poorly understood. Here, we demonstrate that cognitively resilient AD patients, characterized by reduced MAPT/tau pathology, maintain lysosomal integrity, whereas cognitively vulnerable patients, exhibiting greater MAPT/tau burden, display lysosomal dysfunction. Lysosomes in cognitively vulnerable AD brains contain partially digested, seed-competent MAPT/tau species composed mainly of the amyloidogenic core with degraded peripheral regions. These pathogenic MAPT/tau forms are secreted via lysosomal exocytosis, facilitating MAPT/tau propagation and contributing to cognitive decline. Cognitively vulnerable female AD patients show increased lysosome-mediated MAPT/tau secretion relative to their male counterparts. Our findings suggest that lysosomal dysfunction, marked by altered protein expression, pH dysregulation, and MAPT/tau accumulation, underlies the heterogeneity in dementia severity. Targeting lysosomal exocytosis and the amyloidogenic core of MAPT/tau fibrils offer a promising therapeutic avenue to mitigate MAPT/tau pathology and promote cognitive resilience in AD and related dementias. <b>Abbreviation:</b> AD: Alzheimer disease, LAMP1; lysosomal associated membrane protein 1, NFT: neurofibrillary tangles; MAPT: microtubule associated protein tau; PHF: paired helical filaments; TIRF: total internal reflection fluorescence; TARDBP/TDP-43:TAR DNA binding protein.
DOI: 10.6084/m9.figshare.29999871.v1
title: Impaired MAPT/tau-secretory lysosomes are linked to cognitive vulnerability in Alzheimer patients

description: MAPT/tau proteins propagate between brain regions in a prion-like manner, driving the onset and progression of dementia in Alzheimer disease (AD). However, the basis for variability in dementia progression among AD patients remains poorly understood. Here, we demonstrate that cognitively resilient AD patients, characterized by reduced MAPT/tau pathology, maintain lysosomal integrity, whereas cognitively vulnerable patients, exhibiting greater MAPT/tau burden, display lysosomal dysfunction. Lysosomes in cognitively vulnerable AD brains contain partially digested, seed-competent MAPT/tau species composed mainly of the amyloidogenic core with degraded peripheral regions. These pathogenic MAPT/tau forms are secreted via lysosomal exocytosis, facilitating MAPT/tau propagation and contributing to cognitive decline. Cognitively vulnerable female AD patients show increased lysosome-mediated MAPT/tau secretion relative to their male counterparts. Our findings suggest that lysosomal dysfunction, marked by altered protein expression, pH dysregulation, and MAPT/tau accumulation, underlies the heterogeneity in dementia severity. Targeting lysosomal exocytosis and the amyloidogenic core of MAPT/tau fibrils offer a promising therapeutic avenue to mitigate MAPT/tau pathology and promote cognitive resilience in AD and related dementias. <b>Abbreviation:</b> AD: Alzheimer disease, LAMP1; lysosomal associated membrane protein 1, NFT: neurofibrillary tangles; MAPT: microtubule associated protein tau; PHF: paired helical filaments; TIRF: total internal reflection fluorescence; TARDBP/TDP-43:TAR DNA binding protein.
DOI: 10.15468/dl.92p9nq
title: Occurrence Download

description: A dataset containing 2238 species occurrences available in GBIF matching the query:
{
 "and" : [
 "Country is Pakistan",
 "IucnRedListCategory is EN",
 "OccurrenceStatus is Present"
 ]
}

 The dataset includes 2238 records from 90 constituent datasets; see https://api.gbif.org/v1/occurrence/download/0065801-251120083545085/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.29857027
title: Autophagic regulation of ferroportin 1 induces developmental ferroptosis in rice blast

description: The rice blast fungus, <i>Magnaporthe oryzae</i>, imposes a great threat to global food security. Autophagic cell death of conidium is essential for appressorium-mediated host invasion during pathogenesis. Our recent study revealed that ferroptosis, potentially regulated by macroautophagy/autophagy, is responsible for <i>M. oryzae</i> conidial death during appressorium formation and maturation. Here, we characterized the role of the iron exporter MoFpn1 (ferroportin 1) and showed that its loss led to increased intracellular iron levels, accelerated conidial death, and reduced sensitivity to liproxstatin-1, suggesting that MoFpn1 negatively regulates ferroptosis as an iron exporter in <i>M. oryzae</i>. In conidia, MoFpn1-mCherry fusion protein localized on punctate/vesicular organelles, largely overlapping with CMAC-stained vacuoles, and is subject to regulation by iron availability and autophagy. MoFpn1 was associated with Atg8, based on yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays. MoFpn1-mCherry partially colocalized with GFP-Atg8-tagged autophagosomes or autophagic vacuoles in developing conidia. Upon appressorium formation, MoFpn1-mCherry localized to the plasma membrane of appressoria. In mature appressorium, plasma membrane-localized MoFpn1-mCherry transferred to the vacuolar lumen. MoFpn1 also directly interacted with components of the vesicular sorting complex, including the vacuolar SNARE Vam7 that mediates autophagosome-vacuole fusion. Individual deletion of <i>ATG8</i> or <i>VAM7</i> resulted in mislocalization of MoFpn1-mCherry to the vacuolar membrane or multivesicular bodies (MVBs) instead of the vacuolar lumen, under autophagy inducing conditions, or remained on the plasma membrane of the mature appressorium. Overall, our study demonstrates that regulation of the intracellular level of iron by Atg8- and Vam7-mediated autophagy-dependent degradation of MoFpn1 is crucial for conidial death and pathogenicity. <b>Abbreviations:</b> BiFC: bimolecular fluorescence complementation; CMAC: 7-amino-4-chloromethylcoumarin; Fpn1: ferroportin 1; Lip-1: liproxstatin-1; MDA: malondialdehyde; MVBs: multivesicular bodies; SNARE: soluble NSF attachment protein receptor; Y2H: yeast two-hybrid.
DOI: 10.6084/m9.figshare.29857027.v3
title: Autophagic regulation of ferroportin 1 induces developmental ferroptosis in rice blast

description: The rice blast fungus, <i>Magnaporthe oryzae</i>, imposes a great threat to global food security. Autophagic cell death of conidium is essential for appressorium-mediated host invasion during pathogenesis. Our recent study revealed that ferroptosis, potentially regulated by macroautophagy/autophagy, is responsible for <i>M. oryzae</i> conidial death during appressorium formation and maturation. Here, we characterized the role of the iron exporter MoFpn1 (ferroportin 1) and showed that its loss led to increased intracellular iron levels, accelerated conidial death, and reduced sensitivity to liproxstatin-1, suggesting that MoFpn1 negatively regulates ferroptosis as an iron exporter in <i>M. oryzae</i>. In conidia, MoFpn1-mCherry fusion protein localized on punctate/vesicular organelles, largely overlapping with CMAC-stained vacuoles, and is subject to regulation by iron availability and autophagy. MoFpn1 was associated with Atg8, based on yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays. MoFpn1-mCherry partially colocalized with GFP-Atg8-tagged autophagosomes or autophagic vacuoles in developing conidia. Upon appressorium formation, MoFpn1-mCherry localized to the plasma membrane of appressoria. In mature appressorium, plasma membrane-localized MoFpn1-mCherry transferred to the vacuolar lumen. MoFpn1 also directly interacted with components of the vesicular sorting complex, including the vacuolar SNARE Vam7 that mediates autophagosome-vacuole fusion. Individual deletion of <i>ATG8</i> or <i>VAM7</i> resulted in mislocalization of MoFpn1-mCherry to the vacuolar membrane or multivesicular bodies (MVBs) instead of the vacuolar lumen, under autophagy inducing conditions, or remained on the plasma membrane of the mature appressorium. Overall, our study demonstrates that regulation of the intracellular level of iron by Atg8- and Vam7-mediated autophagy-dependent degradation of MoFpn1 is crucial for conidial death and pathogenicity. <b>Abbreviations:</b> BiFC: bimolecular fluorescence complementation; CMAC: 7-amino-4-chloromethylcoumarin; Fpn1: ferroportin 1; Lip-1: liproxstatin-1; MDA: malondialdehyde; MVBs: multivesicular bodies; SNARE: soluble NSF attachment protein receptor; Y2H: yeast two-hybrid.
DOI: 10.6084/m9.figshare.29857027.v2
title: Autophagic regulation of ferroportin 1 induces developmental ferroptosis in rice blast

description: The rice blast fungus, <i>Magnaporthe oryzae</i>, imposes a great threat to global food security. Autophagic cell death of conidium is essential for appressorium-mediated host invasion during pathogenesis. Our recent study revealed that ferroptosis, potentially regulated by macroautophagy/autophagy, is responsible for <i>M. oryzae</i> conidial death during appressorium formation and maturation. Here, we characterized the role of the iron exporter MoFpn1 (ferroportin 1) and showed that its loss led to increased intracellular iron levels, accelerated conidial death, and reduced sensitivity to liproxstatin-1, suggesting that MoFpn1 negatively regulates ferroptosis as an iron exporter in <i>M. oryzae</i>. In conidia, MoFpn1-mCherry fusion protein localized on punctate/vesicular organelles, largely overlapping with CMAC-stained vacuoles, and is subject to regulation by iron availability and autophagy. MoFpn1 was associated with Atg8, based on yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays. MoFpn1-mCherry partially colocalized with GFP-Atg8-tagged autophagosomes or autophagic vacuoles in developing conidia. Upon appressorium formation, MoFpn1-mCherry localized to the plasma membrane of appressoria. In mature appressorium, plasma membrane-localized MoFpn1-mCherry transferred to the vacuolar lumen. MoFpn1 also directly interacted with components of the vesicular sorting complex, including the vacuolar SNARE Vam7 that mediates autophagosome-vacuole fusion. Individual deletion of <i>ATG8</i> or <i>VAM7</i> resulted in mislocalization of MoFpn1-mCherry to the vacuolar membrane or multivesicular bodies (MVBs) instead of the vacuolar lumen, under autophagy inducing conditions, or remained on the plasma membrane of the mature appressorium. Overall, our study demonstrates that regulation of the intracellular level of iron by Atg8- and Vam7-mediated autophagy-dependent degradation of MoFpn1 is crucial for conidial death and pathogenicity. <b>Abbreviations:</b> BiFC: bimolecular fluorescence complementation; CMAC: 7-amino-4-chloromethylcoumarin; Fpn1: ferroportin 1; Lip-1: liproxstatin-1; MDA: malondialdehyde; MVBs: multivesicular bodies; SNARE: soluble NSF attachment protein receptor; Y2H: yeast two-hybrid.
DOI: 10.15468/5scfmx
title: Free-living marine nematodes of the family Sphaerolaimidae (Chromadoria, Monhysterida) from the mangroves of the Qeshm Island, Persian Gulf

description: This dataset contains the digitized treatments in Plazi based on the original journal article Tchesunov, Alexei V., Eskandari, Ali, Hosseinvand, Manouchehr, Hajializadeh, Parima (2024): Free-living marine nematodes of the family Sphaerolaimidae (Chromadoria, Monhysterida) from the mangroves of the Qeshm Island, Persian Gulf. Zootaxa 5468 (3): 523-540, DOI: 10.11646/zootaxa.5468.3.6, URL: http://dx.doi.org/10.11646/zootaxa.5468.3.6AbstractThree species of the family Sphaerolaimidae were found and are described for the first time along the coast of the Qeshm Island. Sphaerolaimus qeshmensis sp. n. is characterized by large body, position of the amphideal fovea at the level of gymnostoma, rather long spicules and presence of dorso-caudal apophysis of the gubernaculum. The new species differs from related S. kleini, S. limosus, S. makrolasius and S. micropapillatus by body length, subcephalic setae length, and other fine details. Sphaerolaimus pumilus sp. n. is characterized by minute body, position of the amphideal fovea posterior to the stegostoma, and short spicules without a gubernaculum. The new species differs from the close S. paragracilis by slightly smaller subcephalic setae arranged in eight groups and total absence of even a vestigial gubernaculum. Parasphaerolaimus brevisetosus found first in mangroves of North Vietnam is redescribed with addition of some important details missed in the original diagnosis. Genera diagnoses of Sphaerolaimus and Parasphaerolaimus are emended and amended. Data on diet of the three studied species are given.