Loomissosa8936

Our findings establish the benefits of antibiotic treated mice for live OCV studies as well as its limitations and underscore the immunogenicity of HaitiV.ImportanceOral cholera vaccines (OCVs) are being deployed to combat cholera but current killed OCVs require multiple doses and show little efficacy in young children. Live OCVs have the potential to overcome these limitations but small animal models for testing OCVs have shortcomings. We used an antibiotic treatment protocol for conventional adult mice to study the effects of short-term colonization by a single dose of HaitiV, a live OCV candidate. Vaccinated mice developed vibriocidal antibodies against V. cholerae and delivered pups that were resistant to cholera, whereas mice vaccinated with inactivated-HaitiV did not. These findings demonstrate HaitiV's immunogenicity and suggest that this antibiotic treatment protocol will be useful for evaluating the efficacy of live OCVs.Objective To scope and summarise available literature on the outcomes of pregnancy and associated factors in sub-Saharan African women with SLE. Methods Electronic databases and reference lists of retrieved articles were searched to identify relevant studies published from 1 January 2000 to 28 October 2019. Data were combined through narrative synthesis. Results We included four studies retrospectively reporting a total of 137 pregnancies in 102 women over a 26-year period. Mean age at conception ranged from 27.2 to 39.9 years. Kidney damage, the predominant organ manifestation before conception, was reported in 43 (42.2%) patients. Ninety-seven (70.8%) pregnancies resulted in 98 live births. SLE flares occurred in 44 (32.2%) pregnancies, mainly skin (20.4%) and renal (18.2%) flares. Major adverse pregnancy outcomes (APOs) were preterm birth 38.8%, low birth weight 29.8%, pregnancy loss 29.2% and pre-eclampsia 24.8%. The main factors associated with APOs were nephritis and SLE flares. Conclusion Over two-thirds of pregnancies resulted in live birth in this cohort of sub-Saharan African women with SLE. The main APOs and associated factors described in other parts of the world are also seen in this region, but with high rates of APOs. A large prospective multinational study is warranted for more compelling evidence.The field of phosphoinositide signaling has expanded significantly in recent years. Phosphoinositides (PIs) are universal signaling molecules that directly interact with membrane proteins or with cytosolic proteins containing domains that directly bind phosphoinositides and are recruited to cell membranes. Through the activities of PI kinases and PI phosphatases, seven distinct phosphoinositide lipid molecules are formed from the parent molecule phosphatidylinositol. PI signals regulate a wide range of cellular functions, including cytoskeletal assembly, membrane binding and fusion, ciliogenesis, vesicular transport, and signal transduction. Given the many excellent reviews on phosphoinositide kinases, phosphoinositide phosphatases, and PIs in general, in this review, we discuss recent studies and advances in PI lipid signaling in the retina. We specifically focus on PI lipids from vertebrate (e.g. bovine, rat, mice, toad, and zebrafish) and invertebrate (e.g. drosophila, horseshoe crab, and squid) retinas. We also discuss the importance of PIs revealed from animal models and human diseases, and methods to study PI levels both in vitro and in vivo. We propose that future studies should investigate the function and mechanism of activation of PI-modifying enzymes/phosphatases and further unravel PI regulation and function in the different cell types of the retina.Phosphatidic acid (PA) phosphatase, encoded by PAH1 in the yeast Saccharomyces cerevisiae, catalyzes the Mg2+-dependent dephosphorylation of PA, producing diacylglycerol at the nuclear/endoplasmic reticulum (ER) membrane. This enzyme plays a major role in triacylglycerol synthesis and in the regulation of phospholipid synthesis. As an interfacial enzyme, PA phosphatase interacts with the membrane surface, binds its substrate, and catalyzes its reaction. The Triton X-100/PA-mixed micellar system has been utilized to examine the activity and regulation of yeast PA phosphatase. This system, however, does not resemble the in vivo environment of the membrane phospholipid bilayer. We developed an assay system that mimics the nuclear/ER membrane to assess PA phosphatase activity. PA was incorporated into unilamellar phospholipid vesicles (liposomes) composed of the major nuclear/ER membrane phospholipids phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine. We optimized this system to support enzyme-liposome interactions and to afford activity that is greater than that obtained with the aforementioned detergent system. Activity was regulated by phospholipid composition, whereas the enzyme's interaction with liposomes was insensitive to composition. OPB-171775 nmr Greater activity was attained with large (> 100 nm) versus small (50 nm) vesicles. The fatty-acyl moiety of PA had no effect on this activity. PA phosphatase activity was dependent on the bulk (hopping mode) and surface (scooting mode) concentrations of PA suggesting a mechanism by which the enzyme operates along the nuclear/ER membrane in vivo.The cytoskeleton consists of polymeric protein filaments with periodic lattices displaying identical binding sites, which establish a multivalent platform for the binding of a plethora of filament-associated ligand proteins. Multivalent ligand proteins can tether themselves to the filaments through one of their binding sites, resulting in an enhanced reaction kinetics for the remaining binding sites. In this Opinion, we discuss a number of cytoskeletal phenomena underpinned by such multivalent interactions, namely (1) generation of entropic forces by filament crosslinkers, (2) processivity of molecular motors, (3) spatial sorting of proteins, and (4) concentration-dependent unbinding of filament-associated proteins. These examples highlight that cytoskeletal filaments constitute the basis for the formation of microenvironments, which cytoskeletal ligand proteins can associate with and, once engaged, can act within at altered reaction kinetics. We thus argue that multivalency is one of the properties crucial for the functionality of the cytoskeleton.