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6,171 results for “mutant”
Original recordings from voltage clamp fluorometry analyses of ANAP-containing P2X7 mutants
<p><span>The large intracellular C-terminus of the pro-inflammatory P2X7 ion channel receptor (P2X7R) is associated with diverse P2X7R-specific functions. Cryo-EM structures of the closed and ATP-bound open full-length P2X7R recently identified a membrane-associated anchoring domain, an open-state stabilizing "cap" domain, and a globular "ballast domain" containing GTP/GDP and dinuclear Zn<sup>2+</sup>-binding sites with unknown functions. To investigate protein dynamics during channel activation, we improved incorporation of the environment-sensitive fluorescent unnatural amino acid L-3-(6-acetylnaphthalen-2-ylamino)-2-aminopropanoic acid (ANAP) into <em>Xenopus</em> <em>laevis</em> oocyte-expressed P2X7Rs and performed voltage clamp fluorometry (VCF). While we confirmed predicted conformational changes within the extracellular and the transmembrane domains, only three out of 41 mutants containing ANAP in the C-terminal domain resulted in ATP-induced fluorescence changes. We conclude that the ballast domain functions rather independently from the extracellular ATP binding domain and might require activation by additional ligands and/or protein interactions. Novel tools to study these are presented.</span></p>
Supplementary data for "The fitness of beta-lactamase mutants depends nonlinearly on resistance level at sublethal antibiotic concentrations."
<p>Supplementary data files and scripts, notes and figures accompanying the manuscript with working title "The fitness of beta-lactamase mutants depends nonlinearly on resistance level at sublethal antibiotic concentrations". The figures and tables this dataset underpins is indicated in the name of each file of the dataset, or in the section "Code and data accessibility" of the manuscript.</p>
DIFFERENTIATION OF ADVANCED GENERATION MUTANT WHEAT LINES: CONVENTIONAL TECHNIQUES VERSUS RAMAN SPECTROSCOPY
<p>Data and codes used in the manuscript titled "DIFFERENTIATION OF ADVANCED GENERATION MUTANT WHEAT LINES: CONVENTIONAL TECHNIQUES VERSUS RAMAN SPECTROSCOPY". The decision tree model is trained and tested using the Classification Learner app of MATLAB (R2021b, The MathWorks, Inc.).</p> <div> </div>
Mapped ATAC-seq data for mock and HSV-1 strain 17 infection and infection with null mutants of HSV-1
<p>Sample annotation:</p> <table> <tbody> <tr> <td>Mock_1</td> <td>mock infection, replicate 1</td> </tr> <tr> <td>Mock_2</td> <td>mock infection, replicate 2</td> </tr> <tr> <td>WT_1</td> <td>HSV-1 wt, strain 17, replicate 1</td> </tr> <tr> <td>WT_2</td> <td>HSV-1 wt, strain 17, replicate 2</td> </tr> <tr> <td>WT_plus_PAA_1</td> <td>HSV-1 wt, strain 17, +PAA, replicate 1</td> </tr> <tr> <td>WT_plus_PAA_2</td> <td>HSV-1 wt, strain 17, +PAA, replicate 2</td> </tr> <tr> <td>dICP0_1</td> <td>HSV-1 lacking expression of ICP0, replicate 1</td> </tr> <tr> <td>dICP0_2</td> <td>HSV-1 lacking expression of ICP0, replicate 2</td> </tr> <tr> <td>dICP22_1</td> <td>HSV-1 lacking expression of ICP22, HSV-1 strain F mutant R325, replicate 1</td> </tr> <tr> <td>dICP22_2</td> <td>HSV-1 lacking expression of ICP22, HSV-1 strain F mutant R325, replicate 2</td> </tr> <tr> <td>dICP22_3</td> <td>HSV-1 lacking expression of ICP22, HSV-1 strain F mutant R325, replicate 3</td> </tr> <tr> <td>dICP22_4</td> <td>HSV-1 lacking expression of ICP22, HSV-1 strain F mutant R325, replicate 4</td> </tr> <tr> <td>dICP22_plus_PAA_1</td> <td>HSV-1 lacking expression of ICP22, HSV-1 strain F mutant R325, +PAA, replicate 1</td> </tr> <tr> <td>dICP22_plus_PAA_2</td> <td>HSV-1 lacking expression of ICP22, HSV-1 strain F mutant R325, +PAA, replicate 2</td> </tr> <tr> <td>dICP27_1</td> <td>HSV-1 lacking expression of ICP27, KOS, replicate 1</td> </tr> <tr> <td>dICP27_2</td> <td>HSV-1 lacking expression of ICP27, KOS, replicate 2</td> </tr> <tr> <td>dVHS_1</td> <td>HSV-1 lacking expression of UL41, replicate 1</td> </tr> <tr> <td>dVHS_2</td> <td>HSV-1 lacking expression of UL41, replicate 2</td> </tr> </tbody> </table>
Dabrafenib plus trametinib versus anti-PD-1 monotherapy as adjuvant therapy in BRAF V600-mutant stage III melanoma after definitive surgery: a prospectively-powered multicenter, retrospective cohort study
<p><strong>Summary </strong></p> <p>Background Both dabrafenib/trametinib (D/T) and anti-PD-1 monotherapy (PD-1) are approved adjuvant therapies for patients with stage III BRAF V600-mutant melanoma. However, there is still a lack of head-to-head comparative data. We aimed to describe efficacy and toxicity outcomes for these two standard therapies across melanoma centers.</p> <p>Methods This prospectively-powered multicenter, retrospective cohort study was conducted in 15 melanoma centers in Australia, China, Germany, Italy, Japan, UK, and US. We included adult patients with resected stage III BRAF V600-mutant melanoma who received either adjuvant D/T or PD-1. The primary endpoint was recurrence-free survival (RFS). Secondary endpoints included overall survival (OS), recurrence pattern and toxicity.</p> <p>Findings We included 598 patients with stage III BRAF V600-mutant melanoma who received either adjuvant D/T (n=393 [66%]) or PD-1 (n=205 [34%]) post definitive surgery between Jul 2015 and Oct 2022. At a median follow-up of 33 months (IQR 21-43), the median RFS was 51∙0 months (95%CI 41∙0-not reached [NR]) in the D/T group, significantly longer than 44∙8 (95%CI 28∙5-NR) in the PD-1 group (univariate: HR 0∙658, 95%CI 0∙498-0∙869, P=0∙003; multivariate: HR 0∙687, 95% CI 0∙512-0∙922, P = 0∙012), with comparable OS with PD-1 (multivariate, HR 1∙011, 95%CI 0∙637-1∙604, P>0∙95). Similar findings were observed using a restricted-mean-survival-time model. D/T survival benefits were consistent in most subgroups, except for older, male patients and those with V600K mutation. Among those who experienced recurrence, the proportion of distant metastases was higher in the D/T cohort. D/T had a higher incidence of treatment modification due to adverse events (AEs) than PD-1, but fewer persistent AEs.</p> <p>Interpretation In patients with stage III BRAF V600-mutant melanoma post definitive surgery, D/T yielded better RFS than PD-1, with higher transient but lower persistent toxicity, and comparable OS. D/T is potentially a superior adjuvant option compared with PD-1. </p>
(Preprocessing) Single-Cell Multi-Omics Identifies Chronic Inflammation as a Driver of TP53 mutant Leukaemic Evolution
<p>Files and scripts for preprocessing of dataset related to our publication titled "Single-Cell Multi-Omics Identifies Chronic Inflammation as a Driver of <em>TP53 </em>mutant Leukaemic Evolution".</p>
Fig. 7. The V19H four-point mutant coupled with T3R in Site directed mutagenesis of Catharanthus roseus (+)-vincadifformine 19-hydroxylase (CYP71BY3) results in two distinct enzymatic functions
Fig. 7. The V19H four-point mutant coupled with T3R converts (¡)-tabersonine to 2,3-dihydro-3-hydroxytabersonine. Traces from in vitro experiments with ()-tabersonine (1) and V19H four-point mutant microsomes or T3O microsomes in the absence or presence of purified recombinant T3R are shown. Yeast microsomes containing the V19H 4-point mutant (red) (V19HL106R–S312T-A376P–F377L) convert ()-tabersonine to tabersonine 2,3-epoxides (5) in the absence of T3R, and to 2,3-dihydro-3-hydroxytabersonine in the presence of T3R. Yeast microsomes containing wild-type T3O (blue) were used as positive controls for tabersonine-2,3-epoxide (5) and 2,3-dihydro-3-hydroxytabersonine biosynthesis in the absence and presence of T3R, respectively. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
Fig. 6 in Characterization of the PRODUCTION of ANTHOCYANIN PIGMENT 1 Arabidopsis dominant mutant using DLEMMA dual isotope labeling approach
Fig. 6. Differential analysis of phenylpropanoid pathway metabolites between WT and pap1-D mutant Arabidopsis leaves. (A) Representation of differential metabolites found between WT and pap1-D in leaves. The data represents geometric fold change mean + standard deviation (SD) of four biological replicates. (B) The phenylpropanoid biosynthetic pathway and metabolites detected in the course of this study. The enzymes highlighted in red are those regulated by the PAP1 transcription factor according to the previous report from Tohge et al. (2005). Dash line denotes multiple enzymatic reactions in the pathway. PAL, phenylalanine ammonia-lyase; C4H, cinnamate 4-hydroxylase; 4CL, 4-coumarate-CoA ligase; CHS, chalcone synthase; CHI, chalcone isomerase; F3H, flavanone 3-hydroxylase; F3′H, flavonoid 3′-hydroxylase; FLS, flavonol synthase; FGT, flavonol glycosyltransferase; DFR, dihydroflavonol reductase; ANS, anthocyanidin synthase; AGT, anthocyani(di)n glycosyltransferase; AAT, anthocyanin acyltransferase. GST, glutathione S-transferase. The pathway was modified from Tohge et al. (2005).
Fig. 5 in Characterization of the PRODUCTION of ANTHOCYANIN PIGMENT 1 Arabidopsis dominant mutant using DLEMMA dual isotope labeling approach
Fig. 5. Linear correlation between labeling efficiency and metabolite location in the phenylpropanoid pathway. The number next to each point corresponds to metabolite location shown in Table 1. 'L' stands for location, the number after 'L' indicates its location in the phenylpropanoid pathway. The number in the bracket is used to distinguish metabolites that are at the same pathway location; LE: labeling efficiency. The color scale represents different percentage of labeling efficiency.
Fig. 2. A in Characterization of the PRODUCTION of ANTHOCYANIN PIGMENT 1 Arabidopsis dominant mutant using DLEMMA dual isotope labeling approach
Fig. 2. A representative example of metabolite identification using DLEMMA. (A) An isotopologue cluster was identified. All information necessary for metabolite identification such as retention time (RT), m/z values and number of labeled atoms, was depicted in a table (B) The raw MS data was first inspected (i.e. RT and m/z values) to validate the results obtained by the Miso software. (C) Elemental composition was then determined using the Masslynx software based on accurate unlabeled m/z and natural isotope patterns. Next, elemental compositions C15H16O9 was searched in SciFinder, and 108 possible candidates were found. The structural information obtained from the labeling patterns was then used to narrow down the number of candidates. Combined with MS/MS information, this metabolite was identified as sinapoyl malate.
Fig. 1 in Characterization of the PRODUCTION of ANTHOCYANIN PIGMENT 1 Arabidopsis dominant mutant using DLEMMA dual isotope labeling approach
Fig. 1. Overview of the DLEMMA workflow employed in this study. (A) Three differently labeled forms of phenylalanine (Phe) were used as feeding precursors, i.e. unlabeled, Label I (Phe-13C), and Label II (Phe-13C2H) Phe. (B) The two Arabidopsis genotype groups, WT and pap1-D, were fed with three forms of labeling 6 6 5 precursors for 24h. (C) Following feeding, the six treatments were combined (i.e. combinations A to F), in which four combinations were designed for metabolite identification and another two for semi-quantitative differential metabolite analysis. The extracts were analyzed by high resolution LC-MS in both positive and negative ion modes. (D) The LC-MS raw data was preprocessed with the R package XCMS, and next the R package Miso was used to detect and extract all Phe-derived mass features. (E) Phe-derived metabolites were identified based on retention time, m/z, MS/MS spectra, and dual-labeling patterns obtained from LC-MS analysis. (F) A combined sample matrices and label-swap approach was used to semi-quantitatively compare phenylpropanoids content between the WT and pap1- D genotypes.
Fig. 3. A in Characterization of the PRODUCTION of ANTHOCYANIN PIGMENT 1 Arabidopsis dominant mutant using DLEMMA dual isotope labeling approach
Fig. 3. A representative example demonstrating metabolite structure elucidation by DLEMMA in cases where multiple different labeling patterns are detected. An isotopologue cluster was detected with multiple different labeling patterns being observed, i.e. m/z+6, m/z+9, m/z+10, m/z+12, m/z+15, m/z+16 and m/z+19. Two possible elemental compositions were found for this metabolite. SciFinder database search revealed that only one structure matched all the 7 observed labeling patterns and this metabolite identified as Cyanidin 3-O-[2-O-(xylosyl)-6-O-(p-coumaroyl) glucoside] 5-O-malonylglucoside.
Fig. 4 in Characterization of the PRODUCTION of ANTHOCYANIN PIGMENT 1 Arabidopsis dominant mutant using DLEMMA dual isotope labeling approach
Fig. 4. Comparison of ion intensities of ferulic acid-hexose detected from phenylalanine fed and non-fed Arabidopsis leaves. (A) Extracted ion chromatogram (1) and mass spectrum (2) of ferulic acid-hexose from non-fed WT Arabidopsis. (B) Extracted ion chromatogram (1) and mass spectrum (2) of ferulic acid-hexose from unlabeled Phe fed WT Arabidopsis. Two isomers of ferulic acid-hexose, eluting at 6.10 and 6.66 min, were detected. The representative mass spectra are from ferulic acid-hexose isomer I (RT = 6.10 min). Peak areas of two ferulic acid-hexose isomers were used to compare their contents between non-fed and un-labeled Phe fed leaves.
Fig. 3 in The toc132toc120 heterozygote mutant of Arabidopsis thaliana accumulates decreased levels of the major chloroplast lipids
Fig. 3. Lipid molecular species in non- and cold-acclimated wildtype and toc132toc120± mutant plants as revealed by ESI-MS/MS. Values are means ± S.D. of 5 biological replicates. Asterisks above the error bars indicate significant difference (P <0.05) when compared to non-acclimated wildtype (Col-0) as determined by student's t-test.
Fig. 2 in The toc132toc120 heterozygote mutant of Arabidopsis thaliana accumulates decreased levels of the major chloroplast lipids
Fig. 2. Expression of nuclear genes that encode plastid (A) and extraplastid (B) enzymes in the wildtype and toc132toc120± mutant plants. The mRNA levels were analyzed by real-time PCR and normalized to the levels of Actin8. The expression levels in the wildtype were set to 1, and values are means ± S.E. of 4 biological replicates. Asterisks above the error bars indicate significant difference (P <0.05) when compared to non-acclimated wildtype (Col-0) as determined by student's t-test.
Fig. 1 in The toc132toc120 heterozygote mutant of Arabidopsis thaliana accumulates decreased levels of the major chloroplast lipids
Fig. 1. Total amount of lipid in each head group class in non- and cold-acclimated wildtype and toc132toc120± mutant plants. Lipid samples were analyzed on a triple quadrupole MS/MS equipped for ESI. Values are means ±S.D. of 5 biological replicates. Asterisks above the error bars indicate significant difference (P <0.05) when compared to non-acclimated wildtype (Col-0) as determined by student's t-test. CA is cold-acclimated plants.
Fig. 4 in The toc132toc120 heterozygote mutant of Arabidopsis thaliana accumulates decreased levels of the major chloroplast lipids
Fig. 4. Changes in lysophospholipids molecular species in non- and cold-acclimated wildtype and toc132toc120± mutant plants as revealed by ESI-MS/MS. Values are means ± S.D. of 5 biological replicates.
Mutant KRAS G12V-specific TCR Transduced T Cell Therapy for Advanced Pancreatic Cancer
ClinicalTrials.gov study NCT04146298. IPD Sharing: Not stated. Countries: 1. Publications: 3.
Intercalating and Maintenance Gefitinib in Combination With Chemotherapy for Advanced EGFR-mutant NSCLC
ClinicalTrials.gov study NCT02299765. IPD Sharing: Not stated. Countries: 1. Publications: 15.
A Study of APR-246 in Combination With Dabrafenib in Resistant Patients With BRAF V600 Mutant Melanoma
ClinicalTrials.gov study NCT03391050. IPD Sharing: Not stated. Countries: 1. Publications: 2.
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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.