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Inferring demographic and selective histories from population genomic data using a two-step approach in species with coding-sparse genomes: an application to human data.
G3 (Bethesda)
January 2025
School of Life Sciences, Center for Evolution & Medicine, Arizona State University, Tempe, AZ 85281, USA.
The demographic history of a population, and the distribution of fitness effects (DFE) of newly arising mutations in functional genomic regions, are fundamental factors dictating both genetic variation and evolutionary trajectories. Although both demographic and DFE inference has been performed extensively in humans, these approaches have generally either been limited to simple demographic models involving a single population, or, where a complex population history has been inferred, without accounting for the potentially confounding effects of selection at linked sites. Taking advantage of the coding-sparse nature of the genome, we propose a 2-step approach in which coalescent simulations are first used to infer a complex multi-population demographic model, utilizing large non-functional regions that are likely free from the effects of background selection.
View Article and Find Full Text PDFFunctional characterization of novel anti-DEFA5 monoclonal antibody clones 1A8 and 4F5 in inflammatory bowel disease colitis tissues.
Inflamm Res
January 2025
Department of Biochemistry, Cancer Biology, Neuroscience, and Pharmacology, School of Medicine, Meharry Medical College, 1005 D.B. Todd Jr. Blvd, Nashville, TN, USA.
Background: The aberrant expression of α defensin 5 (DEFA5) protein in colonic inflammatory bowel diseases (IBDs) underlies the distinct pathogenesis of Crohn's colitis (CC). It can serve as a biomarker for differentiating CC from Ulcerative colitis (UC), particularly in Indeterminate colitis (IC) cases into UC and CC. We evaluated the specificity of commercially available anti-DEFA5 antibodies, emphasizing the need to further validate their appropriateness for a given application and highlighting the necessity for novel antibodies.
View Article and Find Full Text PDFA yeast-based reverse genetics system to generate HCoV-OC43 reporter viruses encoding an eighth subgenomic RNA.
J Virol
January 2025
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
Unlabelled: Coronaviruses have large, positive-sense single-stranded RNA genomes that challenge conventional strategies for mutagenesis. Yeast genetics has been used to manipulate large viral genomes, including those of herpesviruses and coronaviruses. This method, known as transformation-associated recombination (TAR), involves assembling complete viral genomes from dsDNA copies of viral genome fragments via homologous recombination in .
View Article and Find Full Text PDFExtracellular thiol isomerase ERp5 regulates integrin αIIbβ3 activation by inhibition of fibrinogen binding.
Platelets
December 2025
Cyrus Tang Medical Institute, The Fourth Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, China.
Recent studies have shown that anti-ERp5 antibodies inhibit platelet activation and thrombus formation; Moreover, ERp5-deficient platelets exhibit enhanced platelet reactivity via regulation of endoplasmic reticulum (ER) stress. In this study, we used a new ERp5-knockout mouse model as well as recombinant ERp5 (rERp5) protein, to examine the role of ERp5 in platelet function and thrombosis. Although platelet-specific ERp5-deficient mice had decreased platelet count, the mice had shortened tail-bleeding times and enhanced platelet accumulation in FeCl-induced mesenteric artery injury, compared with wild-type mice.
View Article and Find Full Text PDFCase report: Successful therapy with recombinant human vascular endostatin in an elderly man with colon telangiectasia and idiopathic thrombocytopenic purpura.
Front Med (Lausanne)
January 2025
Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China.
An 83-year-old male presented to our Digestive System Department with a 5-day history of severe gastrointestinal (GI) bleeding and a 14-year history of idiopathic thrombocytopenic purpura (ITP) with low platelet levels. Colonoscopy revealed extensive telangiectasias throughout the colon, particularly in the transverse and ascending segments. Standard treatment with proton-pump inhibitors and somatostatin proved ineffective.
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