A Phosphoproteomic Approach towards the Understanding of the Role of TGF-β in Trypanosoma cruzi Biology

Transforming growth factor beta (TGF-β) plays a pivotal role in Chagas disease, not only in the development of chagasic cardiomyopathy, but also in many stages of the T. cruzi life cycle and survival in the host cell environment. The intracellular signaling pathways utilized by T. cruzi to regulate these mechanisms remain unknown. To identify parasite proteins involved in the TGF-β response, we utilized a combined approach of two-dimensional gel electrophoresis (2DE) analysis and mass spectrometry (MS) protein identification. Signaling via TGF-β is dependent on events of phosphorylation, which is one of the most relevant and ubiquitous post-translational modifications for the regulation of gene expression, and especially in trypanosomatids, since they lack several transcriptional control mechanisms. Here we show a kinetic view of T. cruzi epimastigotes (Y strain) incubated with TGF-β for 1, 5, 30 and 60 minutes, which promoted a remodeling of the parasite phosphorylation network and protein expression pattern. The altered molecules are involved in a variety of cellular processes, such as proteolysis, metabolism, heat shock response, cytoskeleton arrangement, oxidative stress regulation, translation and signal transduction. A total of 75 protein spots were up- or down-regulated more than twofold after TGF-β treatment, and from these, 42 were identified by mass spectrometry, including cruzipain–the major T. cruzi papain-like cysteine proteinase that plays an important role in invasion and participates in the escape mechanisms used by the parasite to evade the host immune system. In our study, we observed that TGF-β addition favored epimastigote proliferation, corroborating 2DE data in which proteins previously described to be involved in this process were positively stimulated by TGF-β

Updated cardiovascular prevention guideline of the Brazilian Society of Cardiology: 2019

Sem informação113478788

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

American College of Rheumatology Provisional Criteria for Clinically Relevant Improvement in Children and Adolescents With Childhood-Onset Systemic Lupus Erythematosus

10.1002/acr.23834ARTHRITIS CARE & RESEARCH715579-59

First observation of the decay Lambda(0)(b) -> eta(c) (1S)pK(-)

The decay $\Lambda_b^0 \to \eta_c(1S) p K^-$ is observed for the first time using a data sample of proton-proton collisions, corresponding to an integrated luminosity of 5.5 $fb^{-1}$, collected with the LHCb experiment at a center-of-mass energy of 13 TeV. The branching fraction of the decay is measured, using the $\Lambda_b^0 \to J/\psi p K^-$ decay as a normalization mode, to be $\mathcal{B}(\Lambda_b^0 \to \eta_c(1S) p K^-)=(1.06\pm0.16\pm0.06^{+0.22}_{-0.19})\times10^{-4}$, where the quoted uncertainties are statistical, systematic and due to external inputs, respectively. A study of the $\eta_c(1S) p$ mass spectrum is performed to search for the $P_c(4312)^+$ pentaquark state. No evidence is observed and an upper limit of \begin{equation*} \frac{\mathcal{B}(\Lambda_b^0 \to P_c(4312)^+ K^-)\times \mathcal{B}(P_c(4312)^+ \to \eta_c(1S) p)}{\mathcal{B}(\Lambda_b^0 \to \eta_c(1S) p K^-)} < 0.24 \end{equation*} is obtained at the 95% confidence level.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2020-012.html (LHCb public pages

Searches for 25 rare and forbidden decays of D + and D s + mesons

Abstract: A search is performed for rare and forbidden charm decays of the form Ds+→h±ℓ+ℓ′∓, where h± is a pion or kaon and ℓ(′)± is an electron or muon. The measurements are performed using proton-proton collision data, corresponding to an integrated luminosity of 1.6 fb−1, collected by the LHCb experiment in 2016. No evidence is observed for the 25 decay modes that are investigated and 90 % confidence level limits on the branching fractions are set between 1.4 × 10−8 and 6.4 × 10−6. In most cases, these results represent an improvement on existing limits by one to two orders of magnitude

Search for the doubly heavy Ξ bc 0 baryon via decays to D 0 pK −

Abstract: A search for the doubly heavy Ξbc0 baryon using its decay to the D0pK– final state is performed using proton-proton collision data at a centre-of-mass energy of 13 TeV collected by the LHCb experiment between 2016 and 2018, corresponding to an integrated luminosity of 5.4 fb−1. No significant signal is found in the invariant mass range from 6.7 to 7.2 GeV/c2. Upper limits are set at 95% credibility level on the ratio of the Ξbc0 production cross-section times its branching fraction to D0pK− relative to that of the Λb0→D0pK− decay. The limits are set as a function of the Ξbc0 mass and lifetime hypotheses, in the rapidity range from 2.0 to 4.5 and in the transverse momentum region from 5 to 25 GeV/c. Upper limits range from 1.7 × 10−2 to 3.0 × 10−1 for the considered Ξbc0 mass and lifetime hypotheses