cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.28303093
title: <i>Drosophila</i> aux orchestrates the phosphorylation-dependent assembly of the lysosomal V-ATPase in glia and contributes to SNCA/α-synuclein degradation

description: Glia contribute to the neuropathology of Parkinson disease (PD), but how they react opposingly to be beneficial or detrimental under pathological conditions, like promoting or eliminating SNCA/α-syn (synuclein alpha) inclusions, remains elusive. Here we present evidence that aux (auxilin), the <i>Drosophila</i> homolog of the PD risk factor GAK (cyclin G associated kinase), regulates the lysosomal degradation of SNCA/α-syn in glia. Lack of glial GAK/aux increases the lysosome number and size, regulates lysosomal acidification and hydrolase activity, and ultimately blocks the degradation of substrates including SNCA/α-syn. Whereas SNCA/α-syn accumulates prominently in lysosomes devoid of glial aux, levels of injected SNCA/α-syn preformed fibrils are further enhanced in the absence of microglial GAK. Mechanistically, aux mediates phosphorylation at the serine 543 of Vha44, the V<sub>1</sub> C subunit of the vacuolar-type H<sup>+</sup>-translocating ATPase (V-ATPase), and regulates its assembly to control proper acidification of the lysosomal milieu. Expression of Vha44, but not the Vha44 variant lacking S543 phosphorylation, restores lysosome acidity, locomotor deficits, and DA neurodegeneration upon glial aux depletion, linking this pathway to PD. Our findings identify a phosphorylation-dependent switch controlling V-ATPase assembly for lysosomal SNCA/α-syn degradation in glia. Targeting the clearance of glial SNCA/α-syn inclusions via this lysosomal pathway could potentially be a therapeutic approach to ameliorate the disease progression in PD. <b>Abbreviation</b>: aux: auxilin; GAK: cyclin G associated kinase; LTG: LysoTracker Green; LTR: LysoTracker Red; MR: Magic Red; PD: Parkinson disease; SNCA/a-syn: synuclein alpha; V-ATPase: vacuolar-type H<sup>+</sup>-translocating ATPase
DOI: 10.6084/m9.figshare.28303093.v1
title: <i>Drosophila</i> aux orchestrates the phosphorylation-dependent assembly of the lysosomal V-ATPase in glia and contributes to SNCA/α-synuclein degradation

description: Glia contribute to the neuropathology of Parkinson disease (PD), but how they react opposingly to be beneficial or detrimental under pathological conditions, like promoting or eliminating SNCA/α-syn (synuclein alpha) inclusions, remains elusive. Here we present evidence that aux (auxilin), the <i>Drosophila</i> homolog of the PD risk factor GAK (cyclin G associated kinase), regulates the lysosomal degradation of SNCA/α-syn in glia. Lack of glial GAK/aux increases the lysosome number and size, regulates lysosomal acidification and hydrolase activity, and ultimately blocks the degradation of substrates including SNCA/α-syn. Whereas SNCA/α-syn accumulates prominently in lysosomes devoid of glial aux, levels of injected SNCA/α-syn preformed fibrils are further enhanced in the absence of microglial GAK. Mechanistically, aux mediates phosphorylation at the serine 543 of Vha44, the V<sub>1</sub> C subunit of the vacuolar-type H<sup>+</sup>-translocating ATPase (V-ATPase), and regulates its assembly to control proper acidification of the lysosomal milieu. Expression of Vha44, but not the Vha44 variant lacking S543 phosphorylation, restores lysosome acidity, locomotor deficits, and DA neurodegeneration upon glial aux depletion, linking this pathway to PD. Our findings identify a phosphorylation-dependent switch controlling V-ATPase assembly for lysosomal SNCA/α-syn degradation in glia. Targeting the clearance of glial SNCA/α-syn inclusions via this lysosomal pathway could potentially be a therapeutic approach to ameliorate the disease progression in PD. <b>Abbreviation</b>: aux: auxilin; GAK: cyclin G associated kinase; LTG: LysoTracker Green; LTR: LysoTracker Red; MR: Magic Red; PD: Parkinson disease; SNCA/a-syn: synuclein alpha; V-ATPase: vacuolar-type H<sup>+</sup>-translocating ATPase
DOI: 10.6084/m9.figshare.28030615.v1
title: Endogenous interactomes of MFN1 and MFN2 provide novel insights into interorganelle communication and autophagy

description: MFN1 (mitofusin 1) and MFN2 are key players in mitochondrial fusion, endoplasmic reticulum (ER)-mitochondria juxtaposition, and macroautophagy/autophagy. However, the mechanisms by which these proteins participate in these processes are poorly understood. Here, we studied the interactomes of these two proteins by using CRISPR-Cas9 technology to insert an HA-tag at the C terminus of MFN1 and MFN2, and thus generating HeLa cell lines that endogenously expressed MFN1-HA or MFN2-HA. HA-affinity isolation followed by mass spectrometry identified potential interactors of MFN1 and MFN2. A substantial proportion of interactors were common for MFN1 and MFN2 and were regulated by nutrient deprivation. We validated novel ER and endosomal partners of MFN1 and/or MFN2 with a potential role in interorganelle communication. We characterized RAB5C (RAB5C, member RAS oncogene family) as an endosomal modulator of mitochondrial homeostasis, and SLC27A2 (solute carrier family 27 (fatty acid transporter), member 2) as a novel partner of MFN2 relevant in autophagy. We conclude that MFN proteins participate in nutrient-modulated pathways involved in organelle communication and autophagy.
DOI: 10.6084/m9.figshare.28061871
title: Autophagy induction by piplartine ameliorates axonal degeneration caused by mutant HSPB1 and HSPB8 in Charcot-Marie-Tooth type 2 neuropathies

description: HSPB1 [heat shock protein family B (small) member 1] and HSPB8 are essential molecular chaperones for neuronal proteostasis, as they prevent protein aggregation. Mutant HSPB1 and HSPB8 primarily harm peripheral neurons, resulting in axonal Charcot-Marie-Tooth neuropathies (CMT2). Macroautophagy/autophagy is a shared mechanism by which HSPB1 and HSPB8 mutations cause neuronal dysfunction. Autophagosome formation is reduced in mutant HSPB1-induced pluripotent stem-cell-derived motor neurons from CMT type 2F patients. Likewise, the HSPB8<sup>K141N</sup> knockin mouse model, mimicking CMT type 2 L, exhibits axonal degeneration and muscle atrophy, with SQSTM1/p62-positive deposits. We show here that mouse embryonic fibroblasts isolated from a HSPB8<sup>K141N</sup>/green fluorescent protein (GFP)-LC3 model have diminished autophagosome production under conditions of MTOR inhibition. To correct the autophagic deficits in the HSPB1 and HSPB8 models, we screened by high-throughput autophagosome quantification the repurposing Spectrum Collection library for molecules that could boost the autophagic activity above the canonical MTOR inhibition. Hit compounds were validated on motor neurons obtained by differentiation of HSPB1<sup>P182L</sup> and HSPB8<sup>K141N</sup> patient-derived induced pluripotent stem cells, focusing on autophagy induction as well as neurite network density, axonal degeneration, and mitochondrial morphology. We identified molecules that specifically stimulate autophagosome formation in the HSPB8<sup>K141N</sup> cells, without affecting autophagy flux. Two top lead compounds induced autophagy and reduced axonal degeneration, thus promoting neuronal network maturation in the CMT2 patient-derived motor neurons. Based on these findings, the phenotypical screen revealed that piplartine rescued autophagy deficiencies in both the HSPB1 and HSPB8 models, demonstrating autophagy induction as an effective therapeutic strategy for CMT neuropathies and other chaperonopathies.
DOI: 10.6084/m9.figshare.28061871.v2
title: Autophagy induction by piplartine ameliorates axonal degeneration caused by mutant HSPB1 and HSPB8 in Charcot-Marie-Tooth type 2 neuropathies

description: HSPB1 [heat shock protein family B (small) member 1] and HSPB8 are essential molecular chaperones for neuronal proteostasis, as they prevent protein aggregation. Mutant HSPB1 and HSPB8 primarily harm peripheral neurons, resulting in axonal Charcot-Marie-Tooth neuropathies (CMT2). Macroautophagy/autophagy is a shared mechanism by which HSPB1 and HSPB8 mutations cause neuronal dysfunction. Autophagosome formation is reduced in mutant HSPB1-induced pluripotent stem-cell-derived motor neurons from CMT type 2F patients. Likewise, the HSPB8<sup>K141N</sup> knockin mouse model, mimicking CMT type 2 L, exhibits axonal degeneration and muscle atrophy, with SQSTM1/p62-positive deposits. We show here that mouse embryonic fibroblasts isolated from a HSPB8<sup>K141N</sup>/green fluorescent protein (GFP)-LC3 model have diminished autophagosome production under conditions of MTOR inhibition. To correct the autophagic deficits in the HSPB1 and HSPB8 models, we screened by high-throughput autophagosome quantification the repurposing Spectrum Collection library for molecules that could boost the autophagic activity above the canonical MTOR inhibition. Hit compounds were validated on motor neurons obtained by differentiation of HSPB1<sup>P182L</sup> and HSPB8<sup>K141N</sup> patient-derived induced pluripotent stem cells, focusing on autophagy induction as well as neurite network density, axonal degeneration, and mitochondrial morphology. We identified molecules that specifically stimulate autophagosome formation in the HSPB8<sup>K141N</sup> cells, without affecting autophagy flux. Two top lead compounds induced autophagy and reduced axonal degeneration, thus promoting neuronal network maturation in the CMT2 patient-derived motor neurons. Based on these findings, the phenotypical screen revealed that piplartine rescued autophagy deficiencies in both the HSPB1 and HSPB8 models, demonstrating autophagy induction as an effective therapeutic strategy for CMT neuropathies and other chaperonopathies.
DOI: 10.6084/m9.figshare.28061871.v1
title: Autophagy induction by piplartine ameliorates axonal degeneration caused by mutant HSPB1 and HSPB8 in charcot-marie-tooth type 2 neuropathies

description: HSPB1 [heat shock protein family B (small) member 1] and HSPB8 are essential molecular chaperones for neuronal proteostasis, as they prevent protein aggregation. Mutant HSPB1 and HSPB8 primarily harm peripheral neurons, resulting in axonal Charcot-Marie-Tooth neuropathies (CMT2). Macroautophagy/autophagy is a shared mechanism by which HSPB1 and HSPB8 mutations cause neuronal dysfunction. Autophagosome formation is reduced in mutant HSPB1-induced pluripotent stem-cell-derived motor neurons from CMT type 2F patients. Likewise, the HSPB8<sup>K141N</sup> knockin mouse model, mimicking CMT type 2 L, exhibits axonal degeneration and muscle atrophy, with SQSTM1/p62-positive deposits. We show here that mouse embryonic fibroblasts isolated from a HSPB8<sup>K141N</sup>/green fluorescent protein (GFP)-LC3 model have diminished autophagosome production under conditions of MTOR inhibition. To correct the autophagic deficits in the HSPB1 and HSPB8 models, we screened by high-throughput autophagosome quantification the repurposing Spectrum Collection library for molecules that could boost the autophagic activity above the canonical MTOR inhibition. Hit compounds were validated on motor neurons obtained by differentiation of HSPB1<sup>P182L</sup> and HSPB8<sup>K141N</sup> patient-derived induced pluripotent stem cells, focusing on autophagy induction as well as neurite network density, axonal degeneration, and mitochondrial morphology. We identified molecules that specifically stimulate autophagosome formation in the HSPB8<sup>K141N</sup> cells, without affecting autophagy flux. Two top lead compounds induced autophagy and reduced axonal degeneration, thus promoting neuronal network maturation in the CMT2 patient-derived motor neurons. Based on these findings, the phenotypical screen revealed that piplartine rescued autophagy deficiencies in both the HSPB1 and HSPB8 models, demonstrating autophagy induction as an effective therapeutic strategy for CMT neuropathies and other chaperonopathies.
DOI: 10.60712/si-id361237.1
title: StrainInfo SI-ID 361237.1

description: StrainInfo dataset 361237 about a strain of Burkholderia cenocepacia. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.
DOI: 10.60712/si-id361241.1
title: StrainInfo SI-ID 361241.1

description: StrainInfo dataset 361241 about a strain of Vanrija humicola. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.
DOI: 10.60712/si-id361285.1
title: StrainInfo SI-ID 361285.1

description: StrainInfo dataset 361285 about a strain of Cutaneotrichosporon curvatum. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.
DOI: 10.60712/si-id361286.1
title: StrainInfo SI-ID 361286.1

description: StrainInfo dataset 361286 about a strain of Saccharomyces cerevisiae. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.
DOI: 10.60712/si-id361287.1
title: StrainInfo SI-ID 361287.1

description: StrainInfo dataset 361287 about a strain of Saccharomyces cerevisiae. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.
DOI: 10.60712/si-id361288.1
title: StrainInfo SI-ID 361288.1

description: StrainInfo dataset 361288 about a strain of Kuraishia capsulata. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.
DOI: 10.15468/dl.ojhid8
title: Occurrence Download

description: A dataset containing 14051 species occurrences available in GBIF matching the query:
{
 "TaxonKey" : [
 "is Limodorum abortivum (L.) Sw."
 ]
}

 The dataset includes 14051 records from 115 constituent datasets; see https://api.gbif.org/v1/occurrence/download/0009614-171219132708484/datasets/export for details.
 
Data from some individual datasets included in this download may be licensed under less restrictive terms.
DOI: 10.60712/si-id360092.1
title: StrainInfo SI-ID 360092.1

description: StrainInfo dataset 360092 about a strain of Metschnikowia pulcherrima. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.
DOI: 10.60712/si-id360093.1
title: StrainInfo SI-ID 360093.1

description: StrainInfo dataset 360093 about a strain of Metschnikowia pulcherrima. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.
DOI: 10.60712/si-id360094.1
title: StrainInfo SI-ID 360094.1

description: StrainInfo dataset 360094 about a strain of Nadsonia fulvescens var. elongata. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.
DOI: 10.60712/si-id360095.1
title: StrainInfo SI-ID 360095.1

description: StrainInfo dataset 360095 about a strain of Wickerhamomyces anomalus. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.
DOI: 10.15468/madx42
title: Humber Environmental Data Centre - Humber Environmental Data Centre - Non Sensitive Records from all taxonomic groups

description: NBN Gateway Dataset GA000841
DOI: 10.60712/si-id361242.1
title: StrainInfo SI-ID 361242.1

description: StrainInfo dataset 361242 about a strain of Rhodotorula toruloides. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.
DOI: 10.60712/si-id361243.1
title: StrainInfo SI-ID 361243.1

description: StrainInfo dataset 361243 about a strain of Cryptococcus neoformans var. neoformans. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.
DOI: 10.60712/si-id361244.1
title: StrainInfo SI-ID 361244.1

description: StrainInfo dataset 361244 about a strain of Unidentified. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.
DOI: 10.60712/si-id361290.1
title: StrainInfo SI-ID 361290.1

description: StrainInfo dataset 361290 about a strain of Liquorilactobacillus uvarum. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.
DOI: 10.60712/si-id361291.1
title: StrainInfo SI-ID 361291.1

description: StrainInfo dataset 361291 about a strain of Streptomyces caelestis. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.
DOI: 10.60712/si-id361316.1
title: StrainInfo SI-ID 361316.1

description: StrainInfo dataset 361316 about a strain of Vibrio variabilis. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.
DOI: 10.60712/si-id360097.1
title: StrainInfo SI-ID 360097.1

description: StrainInfo dataset 360097 about a strain of Cystobasidium minutum. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.
DOI: 10.60712/si-id360098.1
title: StrainInfo SI-ID 360098.1

description: StrainInfo dataset 360098 about a strain of Cystobasidium minutum. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.
DOI: 10.60712/si-id361245.1
title: StrainInfo SI-ID 361245.1

description: StrainInfo dataset 361245 about a strain of Salipiger thiooxidans. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.
DOI: 10.60712/si-id361246.1
title: StrainInfo SI-ID 361246.1

description: StrainInfo dataset 361246 about a strain of Cyberlindnera jadinii. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.
DOI: 10.60712/si-id361248.1
title: StrainInfo SI-ID 361248.1

description: StrainInfo dataset 361248 about a strain of Cyberlindnera jadinii. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.
DOI: 10.15468/q1bvt3
title: The InBIO Barcoding Initiative Database: Diptera 01

description: The dataset contains 203 records of Diptera species collected from 2014 to 2018 in continental Portugal (Ferreira et al., 2020). The species represented in the dataset, 154 in total, correspond to about 10% of the known fly diversity of continental Portugal, and contribute to the knowledge on the DNA barcodes and distribution of Portuguese Diptera. Specimens were captured during fieldwork directed specifically for the sampling of Diptera using different methodologies and stored in 96% ethanol. All specimens were morphologically identified to species level. A tissue sample, usually a leg, was collected from each individual, from which DNA was extracted. The DNA barcoding of these specimens was conducted within the InBIO Barcoding Initiative (IBI), funded by EnvMetaGen and PORBIOTA projects. DNA barcode sequences were deposited in BOLD (Barcode of Life Data System) online database. Preserved specimens and DNA extracts are deposited in the IBI collection at the CIBIO (Research Center in Biodiversity and Genetic Resources).
DOI: 10.60712/si-id361249.1
title: StrainInfo SI-ID 361249.1

description: StrainInfo dataset 361249 about a strain of Sporobolomyces roseus. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.
DOI: 10.60712/si-id361317.1
title: StrainInfo SI-ID 361317.1

description: StrainInfo dataset 361317 about a strain of Vibrio maritimus. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.
DOI: 10.60712/si-id361332.1
title: StrainInfo SI-ID 361332.1

description: StrainInfo dataset 361332 about a strain of Acetobacter pasteurianus. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.
DOI: 10.60712/si-id361333.1
title: StrainInfo SI-ID 361333.1

description: StrainInfo dataset 361333 about a strain of Gluconacetobacter diazotrophicus. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.
DOI: 10.60712/si-id361398.1
title: StrainInfo SI-ID 361398.1

description: StrainInfo dataset 361398 about a strain of Corynebacterium renale. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.
DOI: 10.60712/si-id361250.1
title: StrainInfo SI-ID 361250.1

description: StrainInfo dataset 361250 about a strain of Diutina rugosa. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.
DOI: 10.60712/si-id361252.1
title: StrainInfo SI-ID 361252.1

description: StrainInfo dataset 361252 about a strain of Hanseniaspora vineae. StrainInfo is a service developed to provide a resolution of microbial strain identifiers by storing culture collection numbers, their relations, and culture-associated data. StrainInfo is part of NFDI4Microbiota consortium.