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315 results for “MTOR”
Data for: Dysregulation of mTOR signaling mediates common neurite and migration defects in both idiopathic and 16p11.2 deletion autism neural precursor cells
<p>Autism spectrum disorder (ASD) is defined by common behavioral characteristics, raising the possibility of shared pathogenic mechanisms. Yet, vast clinical and etiological heterogeneity suggests personalized phenotypes. Surprisingly, our iPSC studies find that six individuals from two distinct ASD subtypes, idiopathic and 16p11.2 deletion, have common reductions in neural precursor cell (NPC) neurite outgrowth and migration even though whole genome sequencing demonstrates no genetic overlap between the datasets. To identify signaling differences that may contribute to these developmental defects, an unbiased phospho-(p)-proteome screen was performed. Surprisingly, despite the genetic heterogeneity, hundreds of shared p-peptides were identified between autism subtypes including the mTOR pathway. mTOR signaling alterations were confirmed in all NPCs across both ASD subtypes and mTOR modulation rescued ASD phenotypes and reproduced autism NPC-associated phenotypes in control NPCs. Thus, our studies demonstrate that genetically distinct ASD subtypes have common defects in neurite outgrowth and migration which are driven by the shared pathogenic mechanism of mTOR signaling dysregulation.</p>
Data for: Dysregulation of mTOR signaling mediates common neurite and migration defects in both idiopathic and 16p11.2 deletion autism neural precursor cells
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mTOR-iMCD-Blood_Article_Data_Repository
<p>This permanent Zenodo entry corresponds to the original data used for the manuscript: "<strong>Increased mTOR activation in idiopathic multicentric Castleman disease" </strong>accepted for publication by <a href="https://ashpublications.org/blood">Blood</a>. </p> <p>Original data for Figure 5 (proteomics) of the manuscript is available upon reasonable request to the corresponding author of the article.</p>
AAA+ ATPase Thorase Inhibits mTOR Signaling Through the Disassembly of the mTOR Complex 1
<p>The mechanistic target of rapamycin (mTOR) signals through the mTOR complex 1 (mTORC1) and the mTOR complex 2 to maintain cellular and organismal homeostasis. Failure to finely tune mTOR activity results in metabolic dysregulation and disease. While there is substantial understanding of the molecular events leading mTORC1 activation at the lysosome, remarkably little is known about what terminates mTORC1 signaling. Here, we show that the AAA+ ATPase Thorase directly binds mTOR, thereby orchestrating the disassembly and inactivation of mTORC1. Thorase disrupts the association of mTOR to Raptor at the mitochondria-lysosome interface and this action is sensitive to amino acids. Lack of Thorase causes accumulation of mTOR-Raptor complexes and altered mTORC1 disassembly/re-assembly dynamics upon changes in amino acid availability. The resulting excessive mTORC1 can be counteracted with rapamycin <em>in vitro</em> and <em>in vivo</em>. Collectively, we reveal Thorase as a key component of the mTOR pathway that disassembles and thus inhibits mTORC1.</p>
Phosphorylated mTOR targets in the E13.5 mouse brain
<p>Staining of p-S6 S240/244 and p-4EBP1/2 T37/46 in embryonic day 13.5 whole mouse brain, cleared using iDISCO+ </p>
A Pilot Study To Evaluate The Effects of Everolimus on Brain mTOR Activity and Cortical Hyperexcitability in TSC and FCD
ClinicalTrials.gov study NCT02451696. IPD Sharing: Not stated. Countries: 1. Publications: 1.
Cognition, Age, and RaPamycin Effectiveness - DownregulatIon of thE mTor Pathway
ClinicalTrials.gov study NCT04200911. IPD Sharing: YES. Countries: 1. Publications: 1.
Maintenance Rituximab With mTor Inhibition After High-dose Consolidative Therapy in Lymphoma
ClinicalTrials.gov study NCT01665768. IPD Sharing: NO. Countries: 1. Publications: 1.
BEZ235 Phase II Trial in Patients With Advanced Pancreatic Neuroendocrine Tumors (pNET) After Failure of mTOR Inhibitor Therapy.
ClinicalTrials.gov study NCT01658436. IPD Sharing: Not stated. Countries: 9. Publications: 1.
Interleukin-17A signaling promotes CD8+ T cell cytotoxicity against West Nile virus infection through enhancing PI3K-mTOR-mediated metabolism
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AAA+ ATPase Thorase Inhibits mTOR Signaling Through the Disassembly of the mTOR Complex 1
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Effect of fecal microbiota transplantation on diabetic wound healing through the IL-17A-mTOR-HIF1α signaling axis
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Data for: Mouse sperm DNA-methylation changes induced by age and mechanistic target of rapamycin (mTOR) manipulation in Sertoli cells
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Data from: Acute, delayed and chronic remote ischemic conditioning is associated with downregulation of mTOR and enhanced autophagy signaling
Background - Remote ischemic conditioning (RIC), induced by brief periods of limb ischemia has been shown to decrease acute myocardial injury and chronic responses after acute coronary syndromes. While several signaling pathways have been implicated, our understanding of the cardioprotection and its underlying mediators and mechanisms remains incomplete. In this study we examine the effect of RIC on pro- autophagy signaling as a possible mechanism of benefit. Methods and Results - We examined the role of autophagy in the acute/first window (15 minutes after RIC), delayed/second window (24 hours after RIC) and chronic (24 hours after 9 days of repeated RIC) phases of cardioprotection. C57BL/6 mice (N=69) were allocated to each treatment phase and further stratified to receive RIC, induced by four cycles of 5 minutes of limb ischemia followed by 5 minutes of reperfusion, or control treatment consisting solely of handling without transient ischemia. The groups included, group 1 (1W control), group 2 (1W RIC), group 3 (2W control), group 4 (2W RIC), group 5 (3W control) and group 6 (3W RIC). Hearts were isolated for assessment of cardiac function and infarct size after global ischemia using a Langendorff preparation. Infarct size was reduced in all three phases of cardioprotection, in association with improvements in post-ischemic left ventricular end diastolic pressure (LVEDP) and developed pressure (LVDP) (P<0.05). The pattern of autophagy signaling varied; 1W RIC increased AMPK levels and decreased the activation of mammalian target of rapamycin (mTOR), whereas chronic RIC was associated with persistent mTOR suppression and increased levels of autophagosome proteins, LC3II/I and Atg5. Conclusions - Cardioprotection following transient ischemia exists in both the acute and delayed/chronic phases of conditioning. RIC induces pro-autophagy signaling but the pattern of responses varies depending on the phase, with the most complete portfolio of responses observed when RIC is administered chronically.
CRISPuRe-seq: pooled screening of barcoded ribonucleoprotein reporters reveals regulation of RNA polymerase III transcription by the Integrated Stress Response via mTOR
<p>NAR_Data_Package.zip contains the data required for generating figures, including original gel images for western blots and a step-by-step protocol for CRISPuRe-seq.</p> <p>SupplementaryData.xlsx contains all of the Supplemental Data directly referred to in the manuscript.</p> <p>Plasmid maps.zip contains plasmid maps for constructs used in the manuscript in genbank format.</p> <p>Scripts.zip contains the scripts used for screen processing with a text file explaining their usage.</p> <p>Look_Up_Table.zip contains the look-up-table for decoding barcode and sgRNA pairings.</p>
Molecular Alterations Associated With Resistance to Endocrine Therapy and Impacting Treatment With mTOR Inhibitor
ClinicalTrials.gov study NCT02444390. IPD Sharing: UNDECIDED. Countries: 1. Publications: 1.
A Phase II Study With Tumor Molecular Pharmacodynamic (MPD) Evaluation of Oral mTOR-inhibitor Everolimus (RAD001) 10 mg Daily in Patients Suffering From Classic or Endemic Kaposi's Sarcoma
ClinicalTrials.gov study NCT01412515. IPD Sharing: Not stated. Countries: 1. Publications: 0.
Regulation of Lymphocyte Anti-tumor Response in Metastatic Patients Treated With the mTOR Inhibitor Everolimus
ClinicalTrials.gov study NCT02441543. IPD Sharing: UNDECIDED. Countries: 1. Publications: 10.
Study to Compare Vinorelbine In Combination With the mTOR Inhibitor Everolimus vs. Vinorelbin Monotherapy for Second-line Treatment in Advanced Breast Cancer
ClinicalTrials.gov study NCT01520103. IPD Sharing: Not stated. Countries: 1. Publications: 1.
Data from: Acute, delayed and chronic remote ischemic conditioning is associated with downregulation of mTOR and enhanced autophagy signaling
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Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
Annotated Behaviour and Observability Dataset (ABODe)
ABODe is a University of Edinburgh DataShare dataset for behavior classification in group-housed mice using home-cage video, identities, bounding boxes, ground-plate positions, and annotator labels.
DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.