Symmetry Plays a Key Role in the Erasing of Patterned Surface Features

We report on how the relaxation of patterns prepared on a thin film can be controlled by manipu- lating the symmetry of the initial shape. The validity of a lubrication theory for the capillary-driven relaxation of surface profiles is verified by atomic force microscopy measurements, performed on films that were patterned using focused laser spike annealing. In particular, we observe that the shape of the surface profile at late times is entirely determined by the initial symmetry of the perturba- tion, in agreement with the theory. Moreover, in this regime the perturbation amplitude relaxes as a power-law in time, with an exponent that is also related to the initial symmetry. The results have relevance in the dynamical control of topographic perturbations for nanolithography and high density memory storage

S6K2-mediated regulation of TRBP as a determinant of miRNA expression in human primary lymphatic endothelial cells

MicroRNAs (miRNAs) are short non-coding RNAs that silence mRNAs. They are generated following transcription and cleavage by the DROSHA/DGCR8 and DICER/TRBP/PACT complexes. Although it is known that components of the miRNA biogenesis machinery can be phosphorylated, it remains poorly understood how these events become engaged during physiological cellular activation. We demonstrate that S6 kinases can phosphorylate the extended C-terminal domain of TRBP and interact with TRBP in situ in primary cells. TRBP serines 283/286 are essential for S6K-mediated TRBP phosphorylation, optimal expression of TRBP, and the S6K-TRBP interaction in human primary cells. We demonstrate the functional relevance of this interaction in primary human dermal lymphatic endothelial cells (HDLECs). Angiopoietin-1 (ANG1) can augment miRNA biogenesis in HDLECs through enhancing TRBP phosphorylation and expression in an S6K2-dependent manner. We propose that the S6K2/TRBP node controls miRNA biogenesis in HDLECs and provides a molecular link between the mTOR pathway and the miRNA biogenesis machinery

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Computational Treatment of Metalloproteins

Metalloproteins present a considerable challenge for modeling, especially when the starting point is far from thermodynamic equilibrium. Examples include formidable problems such as metalloprotein folding and structure prediction upon metal addition, removal, or even just replacement; metalloenzyme design, where stabilization of a transition state of the catalyzed reaction in the specific binding pocket around the metal needs to be achieved; docking to metal-containing sites and design of metalloenzyme inhibitors. Even more conservative computations, such as elucidations of the mechanisms and energetics of the reaction catalyzed by natural metalloenzymes, are often nontrivial. The reason is the vast span of time and length scales over which these proteins operate, and thus the resultant difficulties in estimating their energies and free energies. It is required to perform extensive sampling, properly treat the electronic structure of the bound metal or metals, and seamlessly merge the required techniques to assess energies and entropies, or their changes, for the entire system. Additionally, the machinery needs to be computationally affordable. Although a great advancement has been made over the years, including some of the seminal works resulting in the 2013 Nobel Prize in chemistry, many aforementioned exciting applications remain far from reach. We review the methodology on the forefront of the field, including several promising methods developed in our lab that bring us closer to the desired modern goals. We further highlight their performance by a few examples of applications

Sodium citrate supplementation enhances tennis skill performance : a crossover, placebo-controlled, double blind study

The efficacy of sodium citrate supplementation (SC) in exercise performance is unclear. Therefore, the aim of this study was to investigate the effect of SC on skilled tennis performance. Ten Brazilian nationally-ranked young male tennis players (age: 17 ± 1 yrs.; stature: 176.7 ± 5.2 cm; body mass: 68.4 ± 7.9 kg) participated in this crossover, placebo-controlled, double-blind study. Upon arrival, at baseline, in both experimental sessions blood was collected, then subjects ingested either sodium citrate (SC - 0.5 g.kg−1BM in capsules of 500 mg) or a placebo (PLA). Two hours later, pre-match blood was collected then skills tests (skill tennis performance test - STPT, repeated-sprint ability shuttle test - RSA) were performed followed by a 1-h simulated match. Immediately following the match, blood was again collected, and STPT, and RSA were administered. All metabolic parameters (i.e. base excess, pH, bicarbonate, and blood lactate) increased (p < 0.001) from baseline to pre-match and post-match in SC condition. Each metabolic parameter was greater (p < 0.001) in SC compared to PLA condition at both pre- and post-match. The SC condition elicited a greater (p < 0.01) shot consistency at post-match in the STPT vs. PLA condition (SC: 58.5 ± 14.8% vs. PLA: 40.4 ± 10.4%). A greater (p < 0.001) amount of games won was observed in the simulated match for SC condition vs. PLA condition (SC: 8.0 ± 1.6 vs. PLA: 6.0 ± 1.7). Additionally, the games won during the simulated match in SC condition was positively correlated with percentage shot consistency (r = 0.67, p < 0.001). The current findings suggest that SC supplementation is an effective ergogenic aid to enhance skilled tennis performance161COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPNão tem2012/19529-9The authors would like to acknowledge all players and coaches involved in this study for their committed participation. RVG would like to thank the CAPES (Brazil) for his scholarship. VCRC would like to thank the FAEPEX (UNICAMP, São Paulo, Brazil) for her scholarship (Grant: 519292 #130/13). This research was supported by FAPESP (Fundação de Amparo à Pesquisa no Estado de São Paulo, São Paulo, Brazil – Grant: 2012/19529-9