Browsing by Subject "Medical research"

Now showing 1 - 3 of 3
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    Extensive dynamic changes in the human transcriptome and its circadian organization during prolonged bed rest
    (Cell Press, 2024-03-15) Archer, Simon N.; Möller-Levet, Carla; Laing, Emma E.; Derk-Jan, Dijk; Bonmatí Carrión, María de los Ángeles; Anatomía Humana y Psicobiología
    Physiological and molecular processes including the transcriptome change across the 24-h day, driven by molecular circadian clocks and behavioral and systemic factors. It is not known how the temporal organization of the human transcriptome responds to a long-lasting challenge. This may, however, provide insights into adaptation, disease, and recovery. We investigated the human 24-h time series transcriptome in 20 individuals during a 90-day constant bed rest protocol. We show that the protocol affected 91% of the transcriptome with 76% of the transcriptome still affected after 10 days of recovery. Dimensionality-reduction approaches revealed that many affected transcripts were associated with mRNA translation and immune function. The number, amplitude, and phase of rhythmic transcripts, including clock genes, varied significantly across the challenge. These findings of long-lasting changes in the temporal organization of the transcriptome have implications for understanding the mechanisms underlying health consequences of conditions such as microgravity and bed rest.
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    Mammalian spermatozoa and cumulus cells bind to a 3D model generated by recombinant zona pellucida protein-coated beads.
    (Springer Nature, 2019-11-29) Hamze Araujo, Julieta Gabriela; Canha-Gouveia, Analuce; Algarra, Blanca; Gómez-Torres, María José; Romar Andrés, Raquel; Jíménez Movilla, María; Olivares Sánchez, María Concepción; Bioquímica y Biología Molecular B e Inmunología; Biotecnología (Universidad de Alicante)
    The egg is a spherical cell encapsulated by the zona pellucida (ZP) which forms a filamentous matrix composed of several glycoproteins that mediate gamete recognition at fertilization. Studies on molecular mechanisms of sperm-egg binding are limited in many mammalian species by the scarcity of eggs, by ethical concerns in harvesting eggs, and by the high cost of producing genetically modified animals. To address these limitations, we have reproduced a three-dimensional (3D) model mimicking the oocyte’s shape, by means of magnetic sepharose beads coated with recombinant ZP glycoproteins (BZP) and cumulus cells. Three preparations composed of either ZP2 (C and N-termini; BZP2), ZP3 (BZP3) or ZP4 (BZP4) were obtained and characterized by protein SDS-PAGE, immunoblot and imaging with confocal and electron microscopy. The functionality of the model was validated by adhesion of cumulus cells, the ability of the glycoprotein-beads to support spermatozoa binding and induce acrosome exocytosis. Thus, our findings document that ZP-beads provide a novel 3D tool to investigate the role of specific proteins on egg-sperm interactions becoming a relevant tool as a diagnostic predictor of mammalian sperm function once transferred to the industry.
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    Neutrophils mediate Salmonella Typhimurium clearance through the GBP4 inflammasome-dependent production of prostaglandins
    (Nature Research, 2016-07-01) Martín Sánchez, María Rosario Fátima; Tyrkalska, Sylwia D.; Candel Camacho, Sergio; Angosto, Diego; Gómez Abellán, Victoria; García Moreno, Diana; Zapata Pérez, Rubén; Sánchez Ferrer, Álvaro; Pelegrín Vivancos, Pablo; Mulero Méndez, Victoriano Francisco; Sepulcre Cortés, María Pilar; Farmacología
    Inflammasomes are cytosolic molecular platforms that alert the immune system about thepresence of infection. Here we report that zebrafish guanylate-binding protein 4 (Gbp4),an IFNg-inducible GTPase protein harbouring a C-terminal CARD domain, is required for theinflammasome-dependent clearance of Salmonella Typhimurium (ST) by neutrophils in vivo.Despite the presence of the CARD domain, Gbp4 requires the universal inflammasomeadaptor Asc for mediating its antibacterial function. In addition, the GTPase activity of Gbp4is indispensable for inflammasome activation and ST clearance. Mechanistically, neutrophilsare recruited to the infection site through the inflammasome-independent production of thechemokine (CXC motif) ligand 8 and leukotriene B4, and then mediate bacterial clearancethrough the Gbp4 inflammasome-dependent biosynthesis of prostaglandin D2. Our resultspoint to GBPs as key inflammasome adaptors required for prostaglandin biosynthesis andbacterial clearance by neutrophils and suggest that transient activation of the inflammasomemay be used to treat bacterial infections.