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Evaluation of Multipeptide Sequences Identified in Silico for the Serological Detection of Antibodies against Vector-Borne Diseases.
Am J Trop Med Hyg
January 2025
Centro de Investigaciones Regionales "Dr. Hideyo Noguchi," Universidad Autónoma de Yucatán, Mérida, México.
The socioecological conditions of Mexican regions are conducive to the spread of vector-borne diseases. Although there are established treatment guidelines for dengue and rickettsiosis, diagnosis is complicated. The objective of this work was to identify epitopes of Rickettsia and dengue virus that could be used in serology screening against vector-borne diseases.
View Article and Find Full Text PDFAntigen receptor ITAMs provide tonic signaling by acting as guanine nucleotide exchange factors to directly activate R-RAS2.
Sci Signal
January 2025
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
The small GTPase R-RAS2 regulates homeostatic proliferation and survival of T and B lymphocytes and, when present in high amounts, drives the development of B cell chronic lymphocytic leukemia. In normal and leukemic lymphocytes, R-RAS2 constitutively binds to antigen receptors through their immunoreceptor tyrosine-based activation motifs (ITAMs) and promotes tonic activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Here, we examined the molecular mechanisms underlying this direct interaction and its consequences for R-RAS2 activity.
View Article and Find Full Text PDFLineage tracing studies suggest that the placenta is not a de novo source of hematopoietic stem cells.
PLoS Biol
January 2025
Cardiovascular Institute and Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Definitive hematopoietic stem and progenitor cells (HSPCs) arise from a small number of hemogenic endothelial cells (HECs) within the developing embryo. Understanding the origin and ontogeny of HSPCs is of considerable interest and potential therapeutic value. It has been proposed that the murine placenta contains HECs that differentiate into HSPCs.
View Article and Find Full Text PDFInvestigating Pb2 CAP-binding domain inhibitors from marine bacteria for targeting the influenza A H5N1.
PLoS One
January 2025
Special Infectious Agents Unit-BSL3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
The ongoing increase in the prevalence and mutation rate of the influenza virus remains a critical global health issue. A promising strategy for antiviral drug development involves targeting the RNA-dependent RNA polymerase, specifically the PB2-cap binding domain of Influenza A H5N1. This study employs an in-silico approach to inhibit this domain, crucial for viral replication, using potential inhibitors derived from marine bacterial compounds.
View Article and Find Full Text PDFEndogenous LRRK2 and PINK1 function in a convergent neuroprotective ciliogenesis pathway in the brain.
Proc Natl Acad Sci U S A
February 2025
Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom.
Mutations in Leucine-rich repeat kinase 2 (LRRK2) and PTEN-induced kinase 1 (PINK1) are associated with familial Parkinson's disease (PD). LRRK2 phosphorylates Rab guanosine triphosphatase (GTPases) within the Switch II domain while PINK1 directly phosphorylates Parkin and ubiquitin (Ub) and indirectly induces phosphorylation of a subset of Rab GTPases. Herein we have crossed LRRK2 [R1441C] mutant knock-in mice with PINK1 knock-out (KO) mice and report that loss of PINK1 does not impact endogenous LRRK2-mediated Rab phosphorylation nor do we see significant effect of mutant LRRK2 on PINK1-mediated Rab and Ub phosphorylation.
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