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347 results for “necrosis”
ETV6 represses Tumor Necrosis Factor During Stress Hematopoiesis to Regulate Mouse Stem Cell Function
<p>At the root of the blood system lies a heterogenous population of hematopoietic stem and progenitor cells (HSPCs), which reside in the bone marrow (BM) and give rise to diverse blood lineages. Maintaining this pool of self-renewing HSPCs is critical to uphold hematopoiesis during period of stress such as bleeding or infection<sup>1</sup>. ETS Variant Transcription Factor 6 (ETV6) is a transcriptional repressor that is highly expressed in HSPCs<sup>2</sup> where it is essential for development and maintenance of the adult hematopoiesis <sup>3</sup>. In 2015, our group<sup>4</sup> and others<sup>5-7</sup> identified germline pathogenic <em>ETV6</em> variants in families with predisposition to B-acute lymphoblastic leukemia (B-ALL) and thrombocytopenia, defining a new genetic syndrome known as Thrombocytopenia 5 (T5). Subsequently, we performed targeted germline <em>ETV6 </em>sequencing of remission blood samples from over 4,000 children with B-ALL and identified germline <em>ETV6</em> variants in ~1% of cases<sup>7</sup>. <em>In vitro</em> studies revealed that ETV6 variant proteins exhibit impaired repressor activity, reduced DNA binding, and aberrant subcellular localization<sup>4,5,7,8</sup>. Overall, these studies indicated that T5-associated germline <em>ETV6</em> variants negatively impact the repressor activity of ETV6. In support of this notion, transcriptional profiling of peripheral blood cells from T5 patients has revealed upregulation of interferon response genes<sup>9</sup>. Nevertheless, little remains known about the mechanisms by which ETV6 regulates the HSPC compartment and how T5-associated <em>ETV6</em> variants contribute to disease.</p> <p> </p> <p>To address these questions, we used CRISPR-Cas9 gene editing to generate a novel mouse model harboring a pathogenic heterozygous germline <em>Etv6 </em>variant, R355X, the murine equivalent to the human T5-associated variant R359X<sup>10</sup>. Through the comprehensive study of this model, we describe a novel role for ETV6 during aging and regenerative hematopoiesis and show that the heterozygous <em>Etv6</em><sup>R355X</sup> variant impairs HSC function <em>in vitro</em> and <em>in vivo</em>. Using genomic approaches to interrogate mouse and human HSCs, we identify new ETV6 targets, including the gene encoding Tumor Necrosis Factor (TNF) and genes involved in TNF signaling. Further, we show increased TNF production and cell cycling in <em>Etv6<sup>R355X/+</sup></em> mouse HSPCs post-BM transplantation. Finally, we demonstrate that genetic ablation of <em>Tnf</em> restores the long-term potential of <em>Etv6<sup>R355X/+</sup></em> cells in serial replating assays <em>in vitro</em>. Together, these findings provide novel insights into the pathways regulated by ETV6 and demonstrate how a pathogenic variant impacts ETV6 function in the context of hematopoietic stress.</p> <p>All bulk RNAseq, Cut&Run, ATACseq, and Hi-C data has been submitted to in the Gene Expression Omnibus (accession number GSE213597) and Sequence Read Archive (BioProject number PRJNA880871). Due to the journal’s limitation on submitted supplementary data as an Excel file, all post-analysis supplemental data files are deposited in Dryad data repository to be made available with this manuscript.</p>
Fig. 2 in Anti-tumour necrosis factor activity in saliva of various tick species and its appearance during the feeding period
Fig. 2. Anti-tumour necrosis factor (TNF) activity in tick salivary glands during feeding. Salivary gland extract (SGE) was prepared from females of Ixodes ricinus (Linnaeus, 1758) either unfed (day 0) or fed for 2, 4, 6 and 8 days. Various concentrations of SGE protein were preincubated for 1.5 h with 2 ng/ml of mouse recombinant TNF before the cytokine ELISA was performed. PBS instead of SGE was added into negative control. Results are presented as the mean ± SD of triplicate wells. *The difference between saliva-treated and untreated group was signif- icant at P <0.05.
A Study to Observe Vedolizumab and Anti-tumour Necrosis Factors (Anti-TNFs) Outcomes in Real-world Biologic Ulcerative Colitis (UC) and Crohn's Disease (CD) Participants
ClinicalTrials.gov study NCT03710486. IPD Sharing: YES. Countries: 2. Publications: 1.
In vivo expression of VCAM1 precedes nephron loss following kidney tubular necrosis
Open the record for dataset details and reuse information.
Annotated necrosis and mitotic figures on 230 rat liver slides of the Open TG-GATEs dataset
<pre># Annotated necrosis and mitotic figures on 230 rat liver slides of the Open TG-GATEs dataset This dataset contains polygonal annotations of 230 whole slide images of the Open TG-GATEs dataset. The annotations were created by Bayer pathologists in a project collaboration between Bayer Pharmaceuticals and Aignostics GmbH. ## Dataset Files This dataset contains only text files which are referring to whole slide images of the Open TG-GATEs dataset. The images are not distributed with this dataset. Image URLs and their respective `md5` checksums are stored in `slides.json`. The annotations are available in the raw json format used in the collaboration as well as in converted [`geojson`](https://geojson.org/) format for easy import into other tools. | file | description | |:-----------------------------------|:-------------------------------------| | slides.json | URLs/md5-checksums of each slide | | annotations/raw/\*.svs.json | original format tissue annotations | | annotations/geojson/\*.svs.geojson | tissue annotations in geojson format | ## Annotated Lesions / Classes The dataset was annotated by 6 expert pathologists with the goal of labelling "Necrosis" and "Mitotic Figures" on rat liver whole slide images. Additional areas in the slides were labelled to improve model training. An overview of the annotated classes is given in the table below: | label | count | area (px^2) | |:---------------------------------------------------|------:|-------------:| | Necrosis (area) | 1576 | 386769004.0 | | Necrosis (single cell) | 1497 | 1624837.5 | | Mitosis | 5205 | 9322482.0 | | Single cell necrosis/apoptosis | 1531 | 1446001.0 | | Central vein | 1125 | 27947588.0 | | Connective tissue | 63 | 8478992.5 | | Dark hepatocytes | 763 | 2516812.5 | | Extramedullary hematopoiesis | 73 | 189508.0 | | Hemorrhage | 142 | 2231979.0 | | Inflammatory infiltrate | 1382 | 9859337.5 | | Large vessels | 224 | 597148962.0 | | Neoplasia | 176 | 478842.5 | | Oval cell/bile duct proliferation | 47 | 1621104.5 | | Parenchyma | 3249 | 673395978.0 | | Portal tract | 1067 | 40819943.0 | | Other lesions | 5 | 9251.0 | | Staining, contamination, and out-of-focus artifact | 46 | 4484697.0 | The pathologists labeled the following number of lesions: | pathologist | annotations | |:--------------|------------:| | pathologist-0 | 15660 | | pathologist-1 | 1749 | | pathologist-2 | 660 | | pathologist-3 | 79 | | pathologist-4 | 22 | | pathologist-5 | 1 | ## Reference The 230 slides of the Open TG-GATEs Pathological Image Database which the annotations refer to are part of the `Toxicogenomics Project and Toxicogenomics Informatics Project under CC Attribution-Share Alike 2.1 Japan` (`CC-BY-SA-2.1-JP`) and are available for download via [10.18908/lsdba.nbdc00954-02-000](http://doi.org/10.18908/lsdba.nbdc00954-02-000). ## License All `*.json` and `*.geojson` files in this distribution are licensed under the same `CC Attribution-Share Alike 2.1 Japan` (`CC-BY-SA-2.1-JP`) license as the Open TG-GATEs Pathological Image Database. The license text is included in the file `LICENSE` in the distribution archive. ## Acknowledgements We thank Dr. Maximilian Alber[^5], Olivér Atanaszov[^5] and Dr. Sharon Ruane[^5] for providing support, the annotation platform, the model training infrastructure and for the great collaboration. We also thank Dr. Yoshinobu Igarashi[^6] for providing insight and advice regarding the dataset and its licensing. [^5]: Aignostics GmbH [^6]: National Institutes of Biomedical Innovation, Health and Nutrition - Toxicogenomics Informatics Project </pre>
A Study Comparing the Efficacy and Safety of Etrolizumab to Infliximab in Participants With Moderate to Severe Ulcerative Colitis Who Are Naïve to Tumor Necrosis Factor (TNF) Inhibitors
ClinicalTrials.gov study NCT02136069. IPD Sharing: YES. Countries: 20. Publications: 2.
Safety and Effectiveness of Live Zoster Vaccine in Anti-Tumor Necrosis Factor (TNF) Users (VERVE Trial)
ClinicalTrials.gov study NCT02538341. IPD Sharing: YES. Countries: 1. Publications: 1.
Tumor Necrosis Factor Inhibition in Focal Segmental Glomerulosclerosis and Treatment Resistant Minimal Change Disease
ClinicalTrials.gov study NCT04009668. IPD Sharing: YES. Countries: 1. Publications: 1.
A Study of the Efficacy and Safety of Etrolizumab in Participants With Ulcerative Colitis Who Have Been Previously Exposed to Tumor Necrosis Factor (TNF) Inhibitors
ClinicalTrials.gov study NCT02100696. IPD Sharing: Not stated. Countries: 24. Publications: 2.
A Study Comparing the Efficacy and Safety of Etrolizumab With Adalimumab and Placebo in Participants With Moderate to Severe Ulcerative Colitis (UC) in Participants Naive to Tumor Necrosis Factor (TNF
ClinicalTrials.gov study NCT02171429. IPD Sharing: Not stated. Countries: 19. Publications: 2.
Study of the Effect of omega3 on Biomarkers of Cardiac Necrosis (CKMB and Troponin I) and Inflammation Marker (CRP) After Elective Percutaneous Coronary Intervention (PCI)
ClinicalTrials.gov study NCT01521845. IPD Sharing: Not stated. Countries: 1. Publications: 1.
Effect of Bevacizumab on Radiation-induced Brain Necrosis in Patients With Nasopharyngeal Carcinoma
ClinicalTrials.gov study NCT01621880. IPD Sharing: Not stated. Countries: 1. Publications: 2.
Study of CP-690,550 Versus Placebo In Rheumatoid Arthritis Patients On Background Methotrexate With Inadequate Response To Tumor Necrosis Factor (TNF) Inhibitors
ClinicalTrials.gov study NCT00960440. IPD Sharing: Not stated. Countries: 14. Publications: 24.
Atacicept in Anti-Tumor Necrosis Factor Alpha-naïve Subjects With Rheumatoid Arthritis (AUGUST II)
ClinicalTrials.gov study NCT00595413. IPD Sharing: Not stated. Countries: 2. Publications: 1.
Safety Study Of Tofacitinib Versus Tumor Necrosis Factor (TNF) Inhibitor In Subjects With Rheumatoid Arthritis
ClinicalTrials.gov study NCT02092467. IPD Sharing: YES. Countries: 30. Publications: 13.
A Study of the Efficacy and Safety of Etrolizumab Treatment in Maintenance of Disease Remission in Ulcerative Colitis (UC) Participants Who Are Naive to Tumor Necrosis Factor (TNF) Inhibitors
ClinicalTrials.gov study NCT02165215. IPD Sharing: Not stated. Countries: 15. Publications: 2.
AXIOS Lumen Apposing Metal Stent for Walled Off Necrosis Drainage IDE Study
ClinicalTrials.gov study NCT03525808. IPD Sharing: Not stated. Countries: 1. Publications: 1.
A Study of Tocilizumab (RoActemra/Actemra) in Patients With Ankylosing Spondylitis Who Have Had an Inadequate Response to Previous Tumor Necrosis Factor (TNF) Antagonist Therapy
ClinicalTrials.gov study NCT01209689. IPD Sharing: Not stated. Countries: 19. Publications: 1.
Trial of Mesna to Prevent Doxorubicin-induced Plasma Protein Oxidation and Tumor Necrosis Factor Alpha (TNF-α) Release
ClinicalTrials.gov study NCT01205503. IPD Sharing: YES. Countries: 1. Publications: 1.
Low Dose Oral Methotrexate in Pediatric Crohn's Disease Patients Initiating Anti-Tumor Necrosis Factor (Anti-TNF) Therapy
ClinicalTrials.gov study NCT02772965. IPD Sharing: NO. Countries: 1. Publications: 1.
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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.