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opencc-by-4.0Apr 2019View details →

Metabolic and Stress Response Changes Precede Disease Onset in the Spinal Cord of Mutant SOD1 ALS Mice

Many Amyotrophic Lateral Sclerosis (ALS) patients experience hypermetabolism, or an increase in measured versus calculated metabolic rate. The cause of hypermetabolism and the effects on neuronal metabolism in ALS are currently unknown, but the efficacy of dietary interventions shows promise for metabolism as an ALS therapeutic target. The goal of this study is to measure changes in metabolic pathways as a function of disease progression in spinal cords of the SOD1G93A mouse model of ALS. We conducted a comprehensive assessment of protein expression for metabolic pathways, antioxidants, chaperones, and proteases in lumbar spinal cord from male SOD1G93A mice at pre-onset, onset, and end-stages of the disease using targeted proteomic analysis. These results reveal that protein content of metabolic proteins including proteins involved in glycolysis, β‐oxidation, and mitochondrial metabolism is altered in SOD1G93A mouse spinal cord well before disease onset. The changes in mitochondrial metabolism proteins are associated with decreased maximal respiration and glycolytic flux in SOD1G93A dermal fibroblasts and increased hydrogen peroxide and lipid hydroperoxide production in mitochondria from sciatic nerve and gastrocnemius muscle fibers at end stage of disease. Consistent with redox dysregulation, expression of the glutathione antioxidant system is decreased, and peroxiredoxins and catalase expression are increased. In addition, stress response proteases and chaperones, including those involved in the mitochondrial unfolded protein response, are induced before disease onset. In summary, we report that metabolic and stress response changes occur in SOD1G93A lumbar spinal cord before motor symptom onset, and are primarily caused by SOD1G93A expression and do not vary greatly as a function of disease course.

opencc-by-4.0Aug 2024View details →

Double mutant stability data and single mutant structures for ThermoMPNN-D paper

Open the record for dataset details and reuse information.

opencc-by-4.0Aug 2024View details →

SNP List of Rice (Nipponbare) MNU Mutant Lines

From the gene names (accessions) and genomic positions listed in the zip file, you can identify the mutant lines that carry specific mutations. The mutant lines are available from the National BioResource Project (NBRP). This list was generated by detecting SNPs using PED from NGS sequences of Nipponbare MNU-treated mutant lines developed at Kyushu University (Kubo et al. 2024). The reference genome used was IRGSP-1.0. The files are organized by chromosome, indicating the positions of mutations and the lines carrying them. Additionally, the mutation positions within the genes indicated by the Rice Annotation Project (RAP) and the primer sequences for amplifying these mutation sites are also included. By searching the files with a gene name, you can identify the mutations within that gene and the lines carrying those mutations. The files are tab-delimited lists that can be imported into Excel. To import, go to the Data tab in Excel, click "From Text/CSV," and select the chromosome file. Column 11 corresponds to the IRGSP accession. You can filter by accession or by the gene abbreviation in Column 10. To obtain seeds, please apply through the seed request page of NBRP (Kyushu University): <a href="https://miriq.agr.kyushu-u.ac.jp/request.php" target="_new" rel="noopener">https://miriq.agr.kyushu-u.ac.jp/request.php</a> Column order is chromosome number, position, line name, ref, alt, genotype, allele frequency, number of reads, mutation type, gene name, RAP ID, position of nucleotide sequence of gene, position of amino acid sequence of gene, left primer, right primer, amplified size. The PED software is available at: <a href="https://github.com/akiomiyao/ped" target="_blank" rel="noopener">https://github.com/akiomiyao/ped</a> Miyao, A., Kiyomiya, J.S., Iida, K. et al. Polymorphic edge detection (PED): two efficient methods of polymorphism detection from next-generation sequencing data. BMC Bioinformatics 20, 362 (2019). <a href="https://bmcbioinformatics.biomedcentral.com/articles/10.1186/s12859-019-2955-6" target="_blank" rel="noopener">https://doi.org/10.1186/s12859-019-2955-6</a>

opencc-zeroDec 2013View details →

Data from: High-throughput genotyping of green algal mutants reveals random distribution of mutagenic insertion sites and endonucleolytic cleavage of transforming DNA

A high-throughput genetic screening platform in a single-celled photosynthetic eukaryote would be a transformative addition to the plant biology toolbox. Here, we present ChlaMmeSeq (Chlamydomonas MmeI-based insertion site Sequencing), a tool for simultaneous mapping of tens of thousands of mutagenic insertion sites in the eukaryotic unicellular green alga Chlamydomonas reinhardtii. We first validated ChlaMmeSeq by in-depth characterization of individual insertion sites. We then applied ChlaMmeSeq to a mutant pool and mapped 11,478 insertions, covering 39% of annotated protein coding genes. We observe that insertions are distributed in a manner largely indistinguishable from random, indicating that mutants in nearly all genes can be obtained efficiently. The data reveal that sequence-specific endonucleolytic activities cleave the transforming DNA and allow us to propose a simple model to explain the origin of the poorly understood exogenous sequences that sometimes surround insertion sites. ChlaMmeSeq is quantitatively reproducible, enabling its use for pooled enrichment screens and for the generation of indexed mutant libraries. Additionally, ChlaMmeSeq allows genotyping of hits from Chlamydomonas screens on an unprecedented scale, opening the door to comprehensive identification of genes with roles in photosynthesis, algal lipid metabolism, the algal carbon-concentrating mechanism, phototaxis, the biogenesis and function of cilia, and other processes for which C. reinhardtii is a leading model system.

opencc-zeroDec 2014View details →

Data from: Systems analysis of adaptive responses to MAP Kinase pathway blockade in BRAF mutant melanoma

Fifty percent of cutaneous melanomas are driven by activated BRAFV600E, but tumors treated with RAF inhibitors, even when they respond dramatically, rapidly adapt and develop resistance. Thus, there is a pressing need to identify the major mechanisms of intrinsic and adaptive resistance and develop drug combinations that target these resistance mechanisms. In a combinatorial drug screen on a panel of 12 treatment-naïve BRAFV600E mutant melanoma cell lines of varying levels of resistance to mitogen-activated protein kinase (MAPK) pathway inhibition, we identified the combination of PLX4720, a targeted inhibitor of mutated BRaf, and lapatinib, an inhibitor of the ErbB family of receptor tyrosine kinases, as synergistically cytotoxic in the subset of cell lines that displayed the most resistance to PLX4720. To identify potential mechanisms of resistance to PLX4720 treatment and synergy with lapatinib treatment, we performed a multi-platform functional genomics analysis to profile the genome as well as the transcriptional and proteomic responses of these cell lines to treatment with PLX4720. We found modest levels of resistance correlated with the zygosity of the BRAF V600E allele and receptor tyrosine kinase (RTK) mutational status. Layered over base-line resistance was substantial upregulation of many ErbB pathway genes in response to BRaf inhibition, thus generating the vulnerability to combination with lapatinib. The transcriptional responses of ErbB pathway genes are associated with a number of transcription factors, including ETS2 and its associated cofactors that represent a convergent regulatory mechanism conferring synergistic drug susceptibility in the context of diverse mutational landscapes.

opencc-zeroAug 2021View details →

Supplementary mass spectonomy data to analyse generation of spliced mutant Kras/RAC2 epitopes

In vitro proteasome processing of neo-splicetopes does not predict their presentation in vivo Proteasome catalyzed peptide splicing (PCPS) of cancer-driving antigens could generate attractive neoepitopes to be targeted by TCR-based adoptive T cell therapy. Based on a spliced peptide prediction algorithm TCRs were generated against putative KRASG12V and RAC2P29L derived neo-splicetopes with high HLA-A*02:01 binding affinity. TCRs generated in mice with a diverse human TCR repertoire specifically recognized the respective target peptides with high efficacy. However, we failed to detect any neo-splicetope specific T cell response when testing the in vivo neo-splicetope generation and obtained no experimental evidence that the putative KRASG12V- and RAC2P29L-derived neo-splicetopes were naturally processed and presented. Furthermore, only the putative RAC2P29L-derived neo-splicetopes was generated by in vitro PCPS. Our experiments pose severe questions on the notion that available algorithms or the in vitro PCPS reaction reliably simulate in vivo splicing and argue against the general applicability of an algorithm-driven "reverse immunology" pipeline for the identification of cancer-specific neo-splicetopes.

opencc-zeroOct 2021View details →

Inner hair cell dysfunction in Klhl18 mutant mice leads to low frequency progressive hearing loss

Age-related hearing loss in humans (presbycusis) typically involves impairment of high frequency sensitivity before becoming progressively more severe at lower frequencies. Pathologies initially affecting lower frequency regions of hearing are less common. Here we describe a progressive, predominantly low-frequency recessive hearing impairment in two mutant mouse lines carrying different mutant alleles of the Klhl18 gene: a spontaneous missense mutation (Klhl18lowf) and a targeted mutation (Klhl18tm1a(KOMP)Wtsi). Both males and females were studied, and the two mutant lines showed similar phenotypes. Threshold for auditory brainstem responses (ABR; a measure of auditory nerve and brainstem neural activity) were normal at 3 weeks old but showed progressive increases from 4 weeks onwards. In contrast, distortion product otoacoustic emission (DPOAE) sensitivity and amplitudes (a reflection of cochlear outer hair cell function) remained normal in mutants. Electrophysiological recordings from the round window of Klhl18lowf mutants at 6 weeks old revealed 1) raised compound action potential thresholds that were similar to ABR thresholds, 2) cochlear microphonic potentials that were normal compared with wildtype and heterozygous control mice and 3) summating potentials that were reduced in amplitude compared to control mice. Scanning electron microscopy showed that Klhl18lowf mutant mice had abnormally tapering of the tips of inner hair cell stereocilia in the apical half of the cochlea while their synapses appeared normal. These results suggest that Klhl18 is necessary to maintain inner hair cell stereocilia and normal inner hair cell function at low frequencies.

opencc-by-4.0Feb 2023View details →

Croissant NOD/ID Mutants

This dataset contains the bytecode of Croissant NOD and ID mutants.

opencc-by-4.0Mar 2023View details →

Croissant OD Mutants

This dataset contains the bytecode of Croissant OD mutants.

opennotspecifiedApr 2021View details →

Fig. 3 in The toc132toc120 heterozygote mutant of Arabidopsis thaliana accumulates decreased levels of the major chloroplast lipids

Fig. 3. (continued).

opennotspecifiedApr 2021View details →

Fig. 3 in The toc132toc120 heterozygote mutant of Arabidopsis thaliana accumulates decreased levels of the major chloroplast lipids

Fig. 3. (continued).

opennotspecifiedApr 2021View details →

Fig. 3 in The toc132toc120 heterozygote mutant of Arabidopsis thaliana accumulates decreased levels of the major chloroplast lipids

Fig. 3. (continued).

Binimetinib and Palbociclib or TAS-102 in Treating Patients With KRAS and NRAS Mutant Metastatic or Unresectable Colorectal Cancer

ClinicalTrials.gov study NCT03981614. IPD Sharing: Not stated. Countries: 1. Publications: 0.

controlledIPD-YESFeb 2026View details →

Study of JDQ443 in Comparison With Docetaxel in Participants With Locally Advanced or Metastatic KRAS G12C Mutant Non-small Cell Lung Cancer

ClinicalTrials.gov study NCT05132075. IPD Sharing: YES. Countries: 25. Publications: 0.

G1T38, a CDK 4/6 Inhibitor, in Combination With Osimertinib in EGFR-Mutant Non-Small Cell Lung Cancer

ClinicalTrials.gov study NCT03455829. IPD Sharing: Not stated. Countries: 1. Publications: 0.

controlledIPD-YESFeb 2026View details →

Testing GDC-0449 (Vismodegib) as Potentially Targeted Treatment in Cancers With Smoothened or Patched 1 Mutant Tumors (MATCH - Subprotocol T)

ClinicalTrials.gov study NCT06357988. IPD Sharing: YES. Countries: 1. Publications: 0.

The Effect of Brushing With Salvadorapersica (Miswak) Sticks on Salivary Streptococcus Mutants and Plaque Level in Children: A Clinical Trial

ClinicalTrials.gov study NCT04137393. IPD Sharing: Not stated. Countries: 0. Publications: 1.

Avelumab With Hypofractionated Radiation Therapy in Adults With Isocitrate Dehydrogenase (IDH) Mutant Glioblastoma

ClinicalTrials.gov study NCT02968940. IPD Sharing: Not stated. Countries: 1. Publications: 0.

Trial of Vemurafenib/Cobimetinib With or Without Bevacizumab in Patients With Stage IV BRAFV600 Mutant Melanoma

ClinicalTrials.gov study NCT01495988. IPD Sharing: Not stated. Countries: 1. Publications: 0.