12 research outputs found
Extreme genetic fragility of the HIV-1 capsid
Genetic robustness, or fragility, is defined as the ability, or lack thereof, of a biological entity to maintain function in the face of mutations. Viruses that replicate via RNA intermediates exhibit high mutation rates, and robustness should be particularly advantageous to them. The capsid (CA) domain of the HIV-1 Gag protein is under strong pressure to conserve functional roles in viral assembly, maturation, uncoating, and nuclear import. However, CA is also under strong immunological pressure to diversify. Therefore, it would be particularly advantageous for CA to evolve genetic robustness. To measure the genetic robustness of HIV-1 CA, we generated a library of single amino acid substitution mutants, encompassing almost half the residues in CA. Strikingly, we found HIV-1 CA to be the most genetically fragile protein that has been analyzed using such an approach, with 70% of mutations yielding replication-defective viruses. Although CA participates in several steps in HIV-1 replication, analysis of conditionally (temperature sensitive) and constitutively non-viable mutants revealed that the biological basis for its genetic fragility was primarily the need to coordinate the accurate and efficient assembly of mature virions. All mutations that exist in naturally occurring HIV-1 subtype B populations at a frequency >3%, and were also present in the mutant library, had fitness levels that were >40% of WT. However, a substantial fraction of mutations with high fitness did not occur in natural populations, suggesting another form of selection pressure limiting variation in vivo. Additionally, known protective CTL epitopes occurred preferentially in domains of the HIV-1 CA that were even more genetically fragile than HIV-1 CA as a whole. The extreme genetic fragility of HIV-1 CA may be one reason why cell-mediated immune responses to Gag correlate with better prognosis in HIV-1 infection, and suggests that CA is a good target for therapy and vaccination strategies
Differentiation and characterization of burrows of two species of armadillos in the Brazilian Cerrado
Influence of Particle Size on Reaction Selectivity in Cyclohexene Hydrogenation and Dehydrogenation over Silica-Supported Monodisperse Pt Particles
Diet of Lontra longicaudis (Olfers, 1818) (Carnivora: Mustelidae) in three limnic systems in Southern Rio Grande do Sul State, Brazil
The aim of the present work was to study the diet of Lontra longicaudis in three limnic systems (anthropogenic shallow lakes, pluvial channel and coastal stream) in Rio Grande do Sul State coastal plain, southern Brazil. Fishes were the most consumed item in all the three systems, being Mugilidae the most representative family in the pluvial channel and coastal stream and Cichlidae in the shallow lakes. Other identified items were mollusks, insects, crustaceans, amphibians, reptiles, birds and mammals and vegetal fragments. The high frequency of birds in the shallow lakes was remarkable, considering the lower frequencies of this item in previous investigations on the species diet. There was a high frequency of swamp eels (Synbranchidae, Synbranchus marmoratus) in the pluvial channel and shallow lakes, which were usually absent or found in low frequencies in previous studies
Reproductive ecology of coypu (Myocastor coypus Molina, 1782) in the Middle Delta of the Paraná River, Argentina
Seed defense biopriming with bacterial cyclodipeptides triggers immunity in cucumber and pepper
Low level expression of the Mitochondrial Antiviral Signaling protein (MAVS) associated with long-term nonprogression in SIV-infected rhesus macaques
High versus low positive end-expiratory pressure during general anaesthesia for open abdominal surgery (PROVHILO trial): a multicentre randomised controlled trial.
Summary
Background The role of positive end-expiratory pressure in mechanical ventilation during general anaesthesia for
surgery remains uncertain. Levels of pressure higher than 0 cm H2O might protect against postoperative pulmonary
complications but could also cause intraoperative circulatory depression and lung injury from overdistension.
We tested the hypothesis that a high level of positive end-expiratory pressure with recruitment manoeuvres protects
against postoperative pulmonary complications in patients at risk of complications who are receiving mechanical
ventilation with low tidal volumes during general anaesthesia for open abdominal surgery.
Methods In this randomised controlled trial at 30 centres in Europe and North and South America, we recruited
900 patients at risk for postoperative pulmonary complications who were planned for open abdominal surgery under
general anaesthesia and ventilation at tidal volumes of 8 mL/kg. We randomly allocated patients to either a high level
of positive end-expiratory pressure (12 cm H2O) with recruitment manoeuvres (higher PEEP group) or a low level of
pressure (2 cm H2O) without recruitment manoeuvres (lower PEEP group). We used a centralised computergenerated
randomisation system. Patients and outcome assessors were masked to the intervention. Primary endpoint
was a composite of postoperative pulmonary complications by postoperative day 5. Analysis was by intention-to-treat.
The study is registered at Controlled-Trials.com, number ISRCTN70332574.
Findings From February, 2011, to January, 2013, 447 patients were randomly allocated to the higher PEEP group
and 453 to the lower PEEP group. Six patients were excluded from the analysis, four because they withdrew consent
and two for violation of inclusion criteria. Median levels of positive end-expiratory pressure were 12 cm H2O
(IQR 12–12) in the higher PEEP group and 2 cm H2O (0–2) in the lower PEEP group. Postoperative pulmonary
complications were reported in 174 (40%) of 445 patients in the higher PEEP group versus 172 (39%) of 449 patients
in the lower PEEP group (relative risk 1·01; 95% CI 0·86–1·20; p=0·86). Compared with patients in the lower PEEP
group, those in the higher PEEP group developed intraoperative hypotension and needed more vasoactive drugs.
Interpretation A strategy with a high level of positive end-expiratory pressure and recruitment manoeuvres during
open abdominal surgery does not protect against postoperative pulmonary complications. An intraoperative protective
ventilation strategy should include a low tidal volume and low positive end-expiratory pressure, without recruitment
manoeuvres