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6,171 results for “mutant”
Phenotype images of the developing heart from wild type and Sox7 mutant mouse embryo
<p><span>The cardiac endothelium influences ventricular chamber development by coordinating trabeculation and compaction. However, the endothelial-specific molecular mechanisms mediating this coordination are not fully understood</span>. Here, we identified the Sox7 transcription factor as a critical cue instructing cardiac endothelium identity during ventricular chamber development. E<span>ndothelial-specific loss of <em>Sox7</em> function in mice results in cardiac ventricular defects similar to non-compaction cardiomyopathy, with a change in the proportions of trabecular and compact cardiomyocytes in the mutant hearts. This phenotype is paralleled by abnormal coronary artery formation. Loss of Sox7 function disrupts the transcriptional regulation of the Notch pathway and connexins 37 and 40, which govern coronary arterial specification. Upon Sox7 endothelial-specific deletion, single-nuclei transcriptomics analysis identified the depletion of a subset of Sox9/Gpc3 positive endocardial progenitor cells and an increase in erythro-myeloid cell lineages. Fate mapping analysis revealed that a subset of Sox7-null endothelial cells transdifferentiate into hematopoietic but not cardiomyocyte lineages. Our findings determine that Sox7 maintains cardiac endothelial cell identity, which is crucial to the cellular cross-talk that drives ventricular compaction and coronary artery development.</span></p>
Excited state observation of active K-Ras reveals differential structural dynamics of wild-type versus oncogenic G12D and G12C mutants
<p>Despite the prominent role of the K-Ras protein in many different types of human cancer, major gaps in atomic-level information severely limit our understanding of K-Ras function in health and disease. Here, we report the quantitative backbone structural dynamics of K-Ras by solution NMR spectroscopy of the active state of wild-type K-Ras·GTP and two of its oncogenic P-loop mutants, G12D and G12C, using a novel nanoparticle-assisted spin relaxation method, relaxation dispersion and chemical exchange saturation transfer experiments covering the entire range of timescales from picosecond to milliseconds. Our combined experiments allow the detection and analysis of the functionally critical Switch I and Switch II regions that have previously remained largely unobservable by X-ray crystallography and NMR spectroscopy. Our data reveal cooperative transitions of K-Ras·GTP to a highly dynamic excited state that closely resembles the partially disordered K-Ras·GDP state. These results advance our understanding of differential GTPase activities and signaling properties of the WT versus mutants and may thus guide new strategies for the development of therapeutics.</p>
High prevalence of lipopolysaccharide mutants and R2-Pyocin susceptible variants in Pseudomonas aeruginosa populations sourced from cystic fibrosis lung infections
<p>Chronic, highly antibiotic-resistant infections in cystic fibrosis (CF) lungs contribute to increasing morbidity and mortality. <em>Pseudomonas</em> <em>aeruginosa</em>, a common CF pathogen, exhibits resistance to multiple antibiotics, contributing to antimicrobial resistance (AMR). These bacterial populations display genetic and phenotypic diversity, but it is unclear how this diversity affects susceptibility to bacteriocins. R-pyocins, i.e. bacteriocins produced by <em>P. aeruginosa</em>, are phage-tail-like antimicrobials. R-pyocins have potential as antimicrobials, however, recent research suggests the diversity of <em>P. aeruginosa</em> variants within CF lung infections leads to varying susceptibility to R-pyocins. This variation may be linked to changes in lipopolysaccharide (LPS), acting as the R-pyocin receptor. Currently, it is unknown how frequently R-pyocin-susceptible strains are in chronic CF lung infection, particularly when considering the heterogeneity within these strains. In this study, we tested R2-pyocin susceptibility of 139 <em>P. aeruginosa</em> variants from 17 sputum samples of seven CF patients and analyzed LPS phenotypes. We found that 83% of sputum samples did not have R2-pyocin-resistant variants, while nearly all samples contained susceptible variants. There was no correlation between LPS phenotype and R2-pyocin susceptibility, though we estimate that about 76% of sputum-derived variants lack an O-specific antigen, 40% lack a common antigen, and 24% have altered LPS cores. The absence of a correlation between LPS phenotype and R-pyocin susceptibility suggests LPS packing density may play a significant role in R-pyocin susceptibility among CF variants. Our research supports the potential of R-pyocins as therapeutic agents, as many infectious CF variants are susceptible to R2-pyocins, even within diverse bacterial populations.</p>
Raw diffraction images of [NiFe]-hydrogenase maturation factor HypD from Aquifex aeolicus (C360S mutant)
<p>HypD is one of the maturation factors of [NiFe]-hydrogenase and can form a complex with other maturation factors (Muraki <em>et al.</em>, 2019). </p> <p>We used datasets to investigate the protocol of detecting polymorphs using Hierarchical clustering (Acta D., submitted). All diffraction datasets were collected at BL45XU, SPring-8, using an automated data collection system <em>ZOO</em>. From six crystals, datasets were collected from each one using a continuous helical scan scheme for 360º oscillation with the following experimental parameters; Beam size: 20 µm × 20 µm, Wavelength: 1.0000 Å, Total dose/crystal: 10 MGy, Detector: EIGER X 9M (DECTRIS Co. Ltd.). All crystals belonged to space group P212121 with unit cell parameters roughly corresponding to a=60.0, b=62.6, c=97.6 Å.</p>
Interactive supplement on all pairwise comparisons carried out for constitutive activating PYL mutant lines
<p>Interactive HTML files on 10 comparisons that were carried out for differential gene expression analyses to understand the impact of constitutive PYL expression on the global gene expression of Arabidopsis thaliana.</p> <p> </p>
Execution times to find strong mutant
<p>A study by Gizzo et al. [1] found that the number of mutants was an inaccurate measure of real computational cost, and that execution times should be used instead. Taking into account this research, the execution time needed by each algorithm to find the S% strong mutants is measured.</p> <p>The document includes a list of runtimes (nanoseconds) for each test case: BruteForce, Ecological Island, SnifferCongestion, and Terminal. At the bottom of each S% for all the algorithms the mean is calculated. Moreover, for each test case, a table with a comparison of the calculated mean is displayed. For each S% strong mutant, the lowest runtime is highlighted.</p> <p>[1] Guizzo G, Sarro F, Harman M (2020) Cost measures matter for mutation testing study validity. In: Proceedings of the 28th ACM Joint Meeting on European Software Engineering Conference and Symposium on the Foundations of Software Engineering, Association for Computing Machinery, New York, NY, USA, ESEC/FSE 2020, p 1127–1139, URL https://doi.org/10.1145/3368089.3409742</p>
Airway environment drives the selection of quorum sensing mutants and promote Staphylococcus aureus chronic lifestyle
<p>Sequence data linked to the manuscript "Airway environment drives the selection of quorum sensing mutants and promote <em>Staph</em><em>ylococcus</em><em> aureus</em> chronic lifestyle"</p> <p>- Shotgun metagenomic from sputa of Patients A B C H J</p> <p>- 10 hemolytic and 10 non-hemolytic isolates from competition assays at day 5</p>
Binimetinib and Hydroxychloroquine in Patients With Advanced KRAS Mutant Non-Small Cell Lung Cancer
ClinicalTrials.gov study NCT04735068. IPD Sharing: Not stated. Countries: 1. Publications: 1.
Study Comparing Combination of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in BRAF Mutant Melanoma
ClinicalTrials.gov study NCT01909453. IPD Sharing: YES. Countries: 29. Publications: 9.
ARIEL4: A Study of Rucaparib Versus Chemotherapy BRCA Mutant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients
ClinicalTrials.gov study NCT02855944. IPD Sharing: Not stated. Countries: 12. Publications: 2.
A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer
ClinicalTrials.gov study NCT04211337. IPD Sharing: YES. Countries: 20. Publications: 3.
S1406 Phase II Study of Irinotecan and Cetuximab With or Without Vemurafenib in BRAF Mutant Metastatic Colorectal Cancer
ClinicalTrials.gov study NCT02164916. IPD Sharing: Not stated. Countries: 1. Publications: 1.
A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Participants With PIK3CA-Mutant, Hormone Receptor-Positive, HER2-Negative
ClinicalTrials.gov study NCT04191499. IPD Sharing: YES. Countries: 28. Publications: 2.
A Study of GSK2118436 in BRAF Mutant Metastatic Melanoma
ClinicalTrials.gov study NCT01153763. IPD Sharing: Not stated. Countries: 5. Publications: 4.
Study of Magrolimab in Combination With Azacitidine Versus Physician's Choice of Venetoclax in Combination With Azacitidine or Intensive Chemotherapy in Patients With TP53 Mutant Acute Myeloid Leukemi
ClinicalTrials.gov study NCT04778397. IPD Sharing: NO. Countries: 15. Publications: 2.
A Study to Assess the Safety and Efficacy of Two Combinations of Isocitrate Dehydrogenase (IDH) Mutant Targeted Therapies Plus Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia (
ClinicalTrials.gov study NCT02677922. IPD Sharing: Not stated. Countries: 14. Publications: 4.
Study of Dacomitinib and Osimertinib for Patients With Advanced EGFR Mutant Lung Cancer
ClinicalTrials.gov study NCT03810807. IPD Sharing: YES. Countries: 1. Publications: 1.
Phase Ib/II Study of Efficacy and Safety of MEK162 and Panitumumab, in Adult mCRC Patients With Mutant or Wild-type RAS Tumors
ClinicalTrials.gov study NCT01927341. IPD Sharing: YES. Countries: 7. Publications: 1.
A FIH Study of PF-07284890 in Participants With BRAF V600 Mutant Solid Tumors With and Without Brain Involvement
ClinicalTrials.gov study NCT04543188. IPD Sharing: NO. Countries: 3. Publications: 1.
Pharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid Tumors
ClinicalTrials.gov study NCT03864042. IPD Sharing: NO. Countries: 5. Publications: 2.
ScienceDex guides
Understand access before you commit
These curated guides explain access requirements, typical timelines, costs, and reuse considerations for widely used research datasets.
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.