Search

Background COVID-19 symptoms vary widely among pregnant women. We aimed to assess the most frequent symptoms amongst pregnant women with SARS-CoV-2 infection in a tertiary hospital in Mexico City. Methods A cross-sectional study of pregnant women attending the National Institute of Perinatology in Mexico City was performed. All women who attended the hospital, despite their symptoms, were tested for SARS-CoV-2. A multivariate-age-adjusted logistic regression was used to assess the association between the main outcome and each characteristic of the clinical history. Results A total of 1880 women were included in the data analysis. Among all women, 30.74% (n = 578) had a positive PCR for SARS-CoV-2 from which 2.7 (n = 50) were symptomatic. Symptoms associated with a positive PCR result were headache (p=.01), dyspnea (p=.043), and myalgia (p=.043). Conclusions At universal screening for SARS-CoV-2, one-third of the population had a positive result, while those symptoms associated with a positive PCR were headache, dyspnea, and myalgia. [ABSTRACT FROM AUTHOR]

Uncovering the plasma membrane distribution of tyrosine kinase Lck is crucial to understanding T lymphocyte triggering. Several studies of Lck species partitioning have given contradictory results. We decided to re-address this point by using phospho-specific antibodies to characterize active and inactive Lck partitioning in raft and non-raft membranes from primary human peripheral blood T lymphocytes. We show that most inactive Lck was localized in rafts and was associated with nearly all CD4 coreceptors and its negative regulator Csk in resting cells, while T cell receptor (TCR) engagement promoted a sustained dephosphorylation of inactive Lck. In contrast, active Lck had a more discrete distribution interacting with only a small number of CD4 coreceptors, and the kinase showed a rapid and short phosphorylation after TCR triggering. The differences in distribution and kinetics may be related to T lymphocyte signalling threshold modulation by Lck species and suggest how TCR triggering is first initiated. This study furthers our knowledge of the TCR activation model in primary human T lymphocytes. Key words: protein kinases, T cell receptor, protein phosphatases, lipid raft, leukocyte-specific protein tyrosine kinase, coreceptor CD4, human. La mise en evidence de la distribution de la tyrosine kinase Lck dans la membrane plasmique est essentielle pour comprendre l'activation des lymphocytes T. Malgre de nombreuses etudes sur le sujet, les resultats sur la repartition de Lck demeurent contradictoires. Nous avons decide de reexaminer cette question et de caracteriser plus en detail, a l'aide d'anticorps phosphospecifiques, la repartition des Lck actives et inactives dans les radeaux lipidiques membranaires et dans les membranes sans radeau de lymphocytes T primaires circulants humains. Nous montrons que la Lck la plus inactive se situe dans les radeaux et qu'elle est associeea presque tous les corecepteurs CD4 et a son regulateur neegatif Csk dans les cellules au repos, alors que l'engagement du RCT favorise une deephosphorylation soutenue de la Lck negative. A l'oppose, la Lck active a une distribution plus discrete, interagissant seulement avec un petit nombre de CD4, et montre une phosphorylation rapide et breve apres l'activation du RCT. Les differences dans la distribution et la cinetique pourraient etre liees a la modulation du seuil de signalisation des lymphocytes T par Lck, et a la maniere dont l'activation du RCT est deeclencheee, ce qui ameliore notre comprehension du modele d'activation du RCT dans un modele de lymphocytes T primaires humains. Mots-cles: proteines kinases, recepteur des cellules T, proteines phosphatases, radeau lipidique, proteine tyrosine kinase specifique des leucocytes, corecepteur CD4, humain. [Traduit par la Redaction], Introduction Communication occurs between T lymphocytes and antigen-presenting cells by a well-organized and dynamic T cell receptor (TCR) signalling machinery. Phosphorylation of the immunoreceptor tyrosine-based activation motifs (ITAMs) in the [...]

Some receptors and signaling molecules, such as Rho-kinase (ROCK), localize in caveolae. We asked whether the function of histamine receptors ([H.sub.1]) and 5-hydroxytryptamine (serotonin) receptors ([5-HT.sub.2A]) in bovine tracheal smooth muscle are modified after caveolae disruption and if so, whether the altered ROCK activity plays a role in this modification. Methyl-β-cyclodextrin (MβCD), used to deplete membrane cholesterol, was shown to disrupt caveolae and diminish sustained contractions to histamine (~80%), 5-HT (100%), a-methyl-5-HT (100%), and KCl (~30%). Cholesterol-loaded MβCD (CL-MβCD) restored the responses to KCl and partially restored the responses to agonists. ROCK inhibition by Y-27632 diminished contractions to histamine (~85%) and 5-HT (~59%). 5-HT or histamine stimulation augmented ROCK activity. These increases were reduced by MβCD and partially reestablished by CL-MβCD. The increase in intracellular [Ca.sup.2+] that was induced by both agonists was reduced by MβCD. The presence of caveolin-1 (Cav-1), [H.sub.1], [5-HT.sub.2A], and ROCK' was corroborated by immunoblotting of membrane fractions from sucrose gradients and by confocal microscopy. [H.sub.1] receptors coimmunoprecipitated with Cav-1 in caveolar and noncaveolar membrane fractions, whereas [5- HT.sub.2A] receptors appeared to be restricted to noncaveolar membrane fractions. We conclude that caveolar and cholesterol integrity are indispensable for the proper functionality of the [H.sub.1] and [5-HT.sub.2A] receptors through their Rho/ROCK signaling. Key words: airway smooth muscle, caveolae, lipid rafts, histamine [H.sub.1] receptor, [5-HT.sub.2A] receptor, Rho- kinase activity. On trouve certains recepteurs et certaines molecules de signalisation, telle la rho-kinase (ROCK), dans les caveoles. Nous avons examine si les fonctions des recepteurs [H.sub.1] et [5-HT.sub.2A] dans le muscle lisse tracheal bovin changent aprs la destruction des caveoles et si l'activite modifiee de la ROCK participe a ces changements. L'emploi de la methyl-β-cyclodextrine (MβCD), pour epuiser le cholesterol membranaire, a detruit les caveoles et diminue les contractions soutenues induites par l'histamine (80 %), la 5-HT (100 %), l'a-methyl 5-HT (100 %) et le KCl (30 %). La MβCD chargee en cholesterol (MβCD-CC) a retabli partiellement les reponses au KCl et aux agonistes. L'inhibition de la ROCK par Y-27672 a diminue les contractions induites par l'histamine (85 %) et la 5-HT (59 %). La stimulation par la 5-HT ou l'histamine a augmente l'activite de la ROCK. Ces augmentations ont ete diminuees par la MβCD et partiellement retablies par la MβCD-CC. L'augmentation de la concentration de [C.sup.2+] intracellulaire induite par les deux agonistes a ete reduite par la MβCD-CC. La presence de caveoline-1 (Cav-1), de [H.sub.1], de [5-HT.sub.2A] et de ROCK' a ete attestee par immunobuvardage de fractions de membranes sur gradients de sucrose et par microscopie confocale. Les recepteurs [H.sub.1] et la Cav-1 coimmunoprecipitent dans les fractions caveolaires et noncaveolaires, alors que les recepteurs [5-HT.sub.2A] ont ete observes dans les fractions noncaveolaires. Nous concluons que l'integrite des caveoles et du cholesterol est indispensable au bon fonctionnement des recepteurs [H.sub.1] et [5-HT.sub.2A] dans la signalisation liee a Rho/ROCK. Mots-cles : caveoles des muscles lisses des voies aeriennes, radeaux lipidiques, recepteur [H.sub.1] de l'histamine, recepteur [5-HT.sub.2A], activite Rho-kinase. [Traduit par la Redaction], Introduction Most agonist-induced contractions in airway smooth muscle are initiated by the activation of specific G protein-coupled receptors (GPCR). Histamine and 5-hydroxytryptamine (serotonin) (5-HT) activate [H.sub.1] and [5-HT.sub.2A] receptors that [...]

Maternal obesity has been related to adverse neonatal outcomes and fetal programming. Oxidative stress and adipokines are potential biomarkers in such pregnancies; thus, the measurement of these molecules has been considered critical. Therefore, we developed artificial neural network (ANN) models based on maternal weight status and clinical data to predict reliable maternal blood concentrations of these biomarkers at the end of pregnancy. Adipokines (adiponectin, leptin, and resistin), and DNA, lipid and protein oxidative markers (8-oxo-2'-deoxyguanosine, malondialdehyde and carbonylated proteins, respectively) were assessed in blood of normal weight, overweight and obese women in the third trimester of pregnancy. A Back-propagation algorithm was used to train ANN models with four input variables (age, pre-gestational body mass index (p-BMI), weight status and gestational age). ANN models were able to accurately predict all biomarkers with regression coefficients greater than R² = 0.945. P-BMI was the most significant variable for estimating adiponectin and carbonylated proteins concentrations (37%), while gestational age was the most relevant variable to predict resistin and malondialdehyde (34%). Age, gestational age and p-BMI had the same significance for leptin values. Finally, for 8-oxo-2'-deoxyguanosine prediction, the most significant variable was age (37%). These models become relevant to improve clinical and nutrition interventions in prenatal care. [ABSTRACT FROM AUTHOR]

Background/Aims: β-Dystroglycan (β-DG) is a transmembrane glycoprotein that links the intracellular cytoskeleton to the extracellular matrix and is crucial for the molecular pathway of lateral force transmission in muscle. We aimed to investigate the effect of decreasing sarcolemmal cholesterol on the distribution of β-DG, its interaction with dystrophin and the impact on the contraction efficiency of muscle. Methods: Isolated rat extensor digitorum longus muscles were incubated with methyl β-cyclodextrin (MβCD) to deplete cholesterol and with MβCD-cholesterol to restore cholesterol. Electric stimulation protocols were used to determine muscle force and fatigue. Detergent- resistant membranes (lipid rafts) were separated from isolated skeletal muscle sarcolemma. The distribution and interactions of β-DG, caveolin-3 and dystrophin were determined by an immunoreactivity analysis. Results: Cholesterol depletion in muscle results in a weakened force of contraction, which recovers after cholesterol restoration. The rate of fatigue is unaffected, but fatigue recovery is dependent upon cholesterol restoration. MβCD modifies the structures of lipid rafts obtained from MβCD-treated muscles by, displacing the membrane proteins β-DG and caveolin-3 f from the lipid raft, thus reducing the interaction of β-DG with dystrophin. Conclusion: Cholesterol depletion weakens the muscle contractile force by disturbing the sarcolemmal distribution of β- dystroglycan and its interaction with dystrophin, two key proteins in the alignment of lateral force transmission pathway. [ABSTRACT FROM AUTHOR]

Enteroaggregative Escherichia coli (EAEC) is an emerging diarrheal pathogen. Many EAEC strains produce the plasmid-encoded toxin (Pet), which exerts cytotoxic effects on human intestinal tissue. Pet-intoxicated HEp-2 cells exhibit rounding and detachment from the substratum, accompanied by loss of F-actin stress fibers and condensation of the spectrin-containing membrane cytoskeleton. Although studies suggest that Pet directly cleaves spectrin, it is not known whether this is the essential mode of action of the toxin. In addition, the effects of Pet on cytoskeletal elements other than actin and spectrin have not been reported. Here, we demonstrate by immunofluorescence that upon Pet intoxication, HEp-2 and HT29 cells lose focal adhesion complexes (FAC), a process that includes the redistribution of focal adhesion kinase (FAK), α-actinin, paxillin, vinculin, F-actin, and spectrin itself. This redistribution was coupled with the depletion of phosphotyrosine labeling at FACs. Immunoblotting and immunoprecipitation experiments revealed that FAK was tyrosine dephosphorylated, before the redistribution of FAK and spectrin. Moreover, phosphatase inhibition blocked cell retraction, suggesting that tyrosine dephosphorylation is an event that precedes FAK cleavage. Finally, we show that in vitro tyrosine-dephosphorylated FAK was susceptible to Pet cleavage. These data suggest that mechanisms other than spectrin redistribution occur during Pet intoxication. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Physiology & Pharmacology is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The sarcoplasmic reticulum (SR) Ca2+ pump is the main homeostatic regulatory mechanism in fast skeletal muscle that maintains intracellular Ca2+ concentration ([Ca2+]i) at the nanomolar level at rest. The transverse tubule (TT) Ca2+ pump transports cytosolic Ca2+ to the extracellular space. During prolonged muscular activity, [Ca2+]i may increase. TT and SR isolated microsomal vesicles were highly purified, and the purity was checked by immunoblotting. The present study shows the effects of endurance exercise on the activities and structures of the TT and SR Ca2+ pumps of fast skeletal muscle from rabbit at rest. The Ca2+ pump activity increased manifolds in TT but did not change in SR. The protein denaturalization profiles obtained by differential scanning calorimetry showed 1) a shift in the transition temperature and an increase in the enthalpy of the TT Ca2+ pump and 2) a significant change in the transition temperature of the SR Ca2+ pump Ca2+-binding domain. We conclude that the TT Ca2+ pump activity was upgraded in association with structural changes to handle the changes in [Ca2+]i and TT lumen Ca2+ concentration that occur during endurance exercise. [ABSTRACT FROM AUTHOR]

The transmembrane phosphatase CD45 regulates both Lck activity and T cell receptor (TCR) signaling. Here we have tested whether the large ectodomain of CD45 has a role in this regulation. A CD45 chimera containing the large ectodomain of CD43 efficiently rescues TCR signaling in CD45null T cells, whereas CD45 chimeras containing small ectodomains from other phosphatases do not. Both basal Lck activity in unstimulated cells and the TCR-induced increase in tyrosine phosphorylation of the TCR ζ-chain and in Lck activity depend on the expression of CD45 with a large ectodomain. Unlike CD45 chimeras containing small ectodomains, both the CD45 chimera with a large ectodomain and wild-type CD45 itself are partially localized to glycosphingolipid-enriched membranes (GEMs). Taken together, these data show that the large CD45 ectodomain is required for optimal TCR signaling. [ABSTRACT FROM AUTHOR]