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  • Vargas McCracken posted an update 3 months, 3 weeks ago

    In human spermatozoa, responsiveness to P in terms of [Ca2+]i increase and AR is highly related to sperm fertilizing ability in vitro, suggesting that the steroid is a physiological inducer of AR during in vitro fertilization. In view of their physiological relevance, P-stimulated sperm functions are currently investigated to develop new tools to select highly performant spermatozoa for assisted reproduction.Sperm migration through the female genital tract is not a quiet journey. Uterine contractions quickly operate a drastic selection, leading to a very restrictive number of sperm reaching the top of uterine horns and finally, provided the presence of key molecules on sperm, the oviduct, where fertilization takes place. During hours and sometimes days before fertilization, subpopulations of spermatozoa interact with dynamic and region-specific maternal components, including soluble proteins, extracellular vesicles and epithelial cells lining the lumen of the female tract. Interactions with uterine and oviductal cells play important roles for sperm survival as they modulate the maternal immune response and allow a transient storage before ovulation. The body of work reported here highlights the importance of sperm interactions with proteins originated from both the uterine and oviductal fluids, as well as hormonal signals around the time of ovulation for sperm acquisition of fertilizing competence.Calcium is an essential ion which regulates sperm motility, capacitation and the acrosome reaction (AR), three processes necessary for successful fertilization. The AR enables the spermatozoon to penetrate into the egg. In order to undergo the AR, the spermatozoon must reside in the female reproductive tract for several hours, during which a series of biochemical transformations takes place, collectively called capacitation. An early event in capacitation is relatively small elevation of intracellular Ca2+ (in the nM range) and bicarbonate, which collectively activate the soluble adenylyl cyclase to produce cyclic-AMP; c-AMP activates protein kinase A (PKA), leading to indirect tyrosine phosphorylation of proteins. During capacitation, there is an increase in the membrane-bound phospholipase C (PLC) which is activated prior to the AR by relatively high increase in intracellular Ca2+ (in the μM range). PLC catalyzes the hydrolysis of phosphatidyl-inositol-4,5-bisphosphate (PIP2) to diacylglycerol and inositol-trisphosphate (IP3), leading to activation of protein kinase C (PKC) and the IP3-receptor. PKC activates a Ca2+- channel in the plasma membrane, and IP3 activates the Ca2+- channel in the outer acrosomal membrane, leading to Ca2+ depletion from the acrosome. As a result, the plasma-membrane store-operated Ca2+ channel (SOCC) is activated to increase cytosolic Ca2+ concentration, enabling completion of the acrosome reaction. The hydrolysis of PIP2 by PLC results in the release and activation of PIP2-bound gelsolin, leading to F-actin dispersion, an essential step prior to the AR. Ca2+ is also involved in the regulation of sperm motility. Tilarginine Acetate During capacitation, the sperm develops a unique motility pattern called hyper-activated motility (HAM) which is essential for successful fertilization. The main Ca2+-channel that mediates HAM is the sperm-specific CatSper located in the sperm tail.

    Carbapenemase-producing Acinetobacter baumannii has been recognized as a critical priority pathogen by the World Health Organization. We hereby report the identification and the draft genome sequence of a carbapenem-resistant A. baumannii isolated from a patient with community-onset urinary tract infection, in a Chilean Patagonian city.

    The whole genome was sequenced on an Illumina NextSeq platform and de novo assembled using Unicycler v.0.4. Resistome analysis and epidemiological investigation (based on MLST data and Pasteur scheme) were performed using bioinformatics tools available from the Center for Genomic Epidemiology.

    The genome size was calculated at 3890824 bp, with a GC content of 39.1%, comprising 3864 total genes, 30 tRNAs, 3 rRNAs, 4 ncRNAs, and 109 pseudogenes. Carbapenem-resistant A. baumannii Ab3_Ch strain belonged to the international sequence type ST15 (clonal complex, CC15), and harboured the ISAba-1-bla

    gene array, along to bla

    and bla

    β-lactamase genes, and aac(3)-IIa and aph(3′)-VIa aminoglycoside resistance genes. Additionally, efflux pump encoding genes (abaF, abaQ, abeS, adeI, adeK, adeL, adeN, adeR, adeS, and amvA) were identified, and mutations in the quinolone resistance-determining region of gyrA (Ser81Leu) and parC (Ser84Leu) were considered responsible for fluoroquinolone resistance.

    This genome sequence data could be used for comparative genomic studies of critical priority A. baumannii strains, as well as to understand the specific features of hospital-associated A. baumannii lineages of international clonal complexes emerging in community settings.

    This genome sequence data could be used for comparative genomic studies of critical priority A. baumannii strains, as well as to understand the specific features of hospital-associated A. baumannii lineages of international clonal complexes emerging in community settings.

    The Singapore GSDCS score was developed to enable clinicians predict the risk of nosocomial multidrug-resistant Gram-negative bacilli (RGNB) infection in critically ill patients. We aimed to validate this score in a UK setting.

    A retrospective case-control study was conducted including patients who stayed for more than 24h in intensive care units (ICUs) across two tertiary National Health Service hospitals in London, UK (April 2011-April 2016). Cases with RGNB and controls with sensitive Gram-negative bacilli (SGNB) infection were identified.

    The derived GSDCS score was calculated from when there was a step change in antimicrobial therapy in response to clinical suspicion of infection as follows prior Gram-negative organism, Surgery, Dialysis with end-stage renal disease, prior Carbapenem use and intensive care Stay of more than 5 days. A total of 110 patients with RGNB infection (cases) were matched 11 to 110 geotemporally chosen patients with SGNB infection (controls). The discriminatory ability of the prediction tool by receiver operating characteristic curve analysis in our validation cohort was 0.

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