Peptide:lipid ratio and membrane surface charge determine the mechanism of action of the antimicrobial peptide BP100. Conformational and functional studies

The cecropin-melittin hybrid antimicrobial peptide BP100 (H-KKLFKKILKYL-NH2) is selective for Gram-negative bacteria, negatively charged membranes, and weakly hemolytic. We studied BP100 conformational and functional properties upon interaction with large unilamellar vesicles, LUVs, and giant unilamellar vesicles, GUVs, containing variable proportions of phosphatidylcholine (PC) and negatively charged phosphatidylglycerol (PG). CD and NMR spectra showed that upon binding to PG-containing LUVs BP100 acquires a-helical conformation, the helix spanning residues 3-11. Theoretical analyses indicated that the helix is amphipathic and surface-seeking. CD and dynamic light scattering data evinced peptide and/or vesicle aggregation, modulated by peptide: lipid ratio and PG content. BP100 decreased the absolute value of the zeta potential () of LUVs with low PG contents; for higher PG, binding was analyzed as an ion-exchange process. At high salt, BP100-induced LUVS leakage requires higher peptide concentration, indicating that both electrostatic and hydrophobic interactions contribute to peptide binding. While a gradual release took place at low peptide:lipid ratios, instantaneous loss occurred at high ratios, suggesting vesicle disruption. Optical microscopy of GUVs confirmed BP100-promoted disruption of negatively charged membranes. the mechanism of action of BP100 is determined by both peptide:lipid ratio and negatively charged lipid content While gradual release results from membrane perturbation by a small number of peptide molecules giving rise to changes in acyl chain packing, lipid clustering (leading to membrane defects), and/or membrane thinning, membrane disruption results from a sequence of events large-scale peptide and lipid clustering, giving rise to peptide-lipid patches that eventually would leave the membrane in a carpet-like mechanism. (C) 2014 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Institut Nacional de Ciencia e Tecnologia de fluidos complexos (INCTFCx)Nude de Apoio Pesquisa de Fluidos Complexos (NAPFCx)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ São Paulo, Inst Chem, Dept Biochem, BR-05513970 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, BR-04044020 São Paulo, BrazilUniv Fed Rio de Janeiro, Inst Med Biochem, Nucl Magnet Resonance Natl Ctr, Rio de Janeiro, BrazilEmbrapa Recursos Genet & Biotecnol, BR-70770917 Brasilia, DF, BrazilUniversidade Federal de São Paulo, Dept Biophys, BR-04044020 São Paulo, BrazilFAPESP: 2007/50970-5FAPESP: 2013/08166-5Web of Scienc

ACE2-angiotensin-(1-7)-Mas axis in renal ischaemia/reperfusion injury in rats

AngII (angiotensin II), ACE (angiotensin I-converting enzyme) and the AT(1) receptor (AngII type I receptor) are associated with the inflammatory process and microvascular dysfunction of AKI (acute kidney injury) induced by renal I/R (ischaemia/reperfusion). However, Ang-(1-7) [angiotensin-(1-7)], ACE2 (angiotensin I-converting enzyme 2) and the Mas receptor also play a role in renal disease models. Therefore, in the present study, we have examined the renal profile of Ang-(1-7), ACE2 and the Mas receptor in renal I/R and compared them with that of AngII, ACE and the AT(1) receptor. Male Wistar rats were submitted to left nephrectomy and ischaemia (45 min) followed by reperfusion (2 or 4 h) in the right kidney. At 4 h of reperfusion, renal AngII was increased (P < 0.01) and renal Ang-(1-7) was decreased substantially (P < 0.05), although plasma levels of both angiotensins were unchanged. in addition, renal I/R decreased the renal mRNA expression of renin (P < 0.05), AT(1) receptors (P < 0.001) and ACE2 (P < 0.05). At 2 and 4 h of reperfusion, renal ACE activity was reduced (P < 0.05). On the other hand, renal expression of the Mas receptor was greatly increased at 4 h of reperfusion (P < 0.01), which was confirmed by immunohistochemical and Western blot analysis. in conclusion, increased renal expression of the Mas receptor associated with changes in the RAS (renin-angiotensin-system)-related peptidases support an important role for the ACE2 Ang-(1-7) Mas axis in AKI.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Univ Fed Minas Gerais, Inst Biol Sci, Dept Physiol & Biophys, BR-31270901 Belo Horizonte, MG, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04044020 São Paulo, SP, BrazilUniv Fed Minas Gerais, Dept Pathol, BR-31270901 Belo Horizonte, MG, BrazilUniv Fed Minas Gerais, Dept Microbiol, BR-31270901 Belo Horizonte, MG, BrazilUniv Fed Minas Gerais, Clin Pathol Unit COLTEC, BR-31270901 Belo Horizonte, MG, BrazilUniv Fed Minas Gerais, Dept Biochem, Inst Biol Sci, BR-31270901 Belo Horizonte, MG, BrazilUniv Fed Minas Gerais, Dept Pediat, Fac Med, BR-31270901 Belo Horizonte, MG, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04044020 São Paulo, SP, BrazilCAPES: PRDEX2009CNPq: 8701480/1997-4FAPEMIG: CBS 2044/96Web of Scienc

ERICA: patterns of alcohol consumption in Brazilian adolescents

ABSTRACT OBJECTIVE To describe the patterns of alcohol consumption in Brazilian adolescents. METHODS We investigated adolescents who participated in the Study of Cardiovascular Risks in Adolescents (ERICA). This is a cross-sectional, national and school-based study, which surveyed adolescents of 1,247 schools from 124 Brazilian municipalities. Participants answered a self-administered questionnaire with a section on alcoholic beverages consumption. Measures of relative frequency (prevalence), and their 95% confidence intervals, were estimated for the following variables: use of alcohol beverages in the last 30 days, frequency of use, number of glasses or doses consumed in the period, age of the first use of alcohol, and most consumed type of drink. Data were estimated for country and macro-region, sex, and age group. The module survey of the Stata program was used for data analysis of complex sample. RESULTS We evaluated 74,589 adolescents, who accounted for 72.9% of eligible students. About 1/5 of adolescents consumed alcohol at least once in the last 30 days and about 2/3 in one or two occasions during this period. Among the adolescents who consumed alcoholic beverages, 24.1% drank it for the first time before being 12 years old, and the most common type of alcoholic beverages consumed by them were drinks based on vodka, rum or tequila, and beer. CONCLUSIONS There is a high prevalence of alcohol consumption among adolescents, as well as their early onset of alcohol use. We also identified a possible change in the preferred type of alcoholic beverages compared with previous research

Relationship among medical student resilience, educational environment and quality of life

Resilience is a capacity to face and overcome adversities, with personal transformation and growth. In medical education, it is critical to understand the determinants of a positive, developmental reaction in the face of stressful, emotionally demanding situations. We studied the association among resilience, quality of life (QoL) and educational environment perceptions in medical students. We evaluated data from a random sample of 1,350 medical students from 22 Brazilian medical schools. Information from participants included the Wagnild and Young's resilience scale (RS-14), the Dundee Ready Educational Environment Measure (DREEM), the World Health Organization Quality of Life questionnaire - short form (WHOQOL-BREF), the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI). Full multiple linear regression models were adjusted for sex, age, year of medical course, presence of a BDI score >= 14 and STAI state or anxiety scores >= 50. Compared to those with very high resilience levels, individuals with very low resilience had worse QoL, measured by overall (beta=-0.89; 95% confidence interval =-1.21 to -0.56) and medical-school related (beta=-0.85; 95% CI=-1.25 to -0.45) QoL scores, environment (beta=-6.48; 95% CI=-10.01 to -2.95), psychological (beta=-22.89; 95% CI=-25.70 to -20.07), social relationships (beta=-14.28; 95% CI=-19.07 to -9.49), and physical health (beta=-10.74; 95% CI=-14.07 to -7.42) WHOQOL-BREF domain scores. They also had a worse educational environment perception, measured by global DREEM score (beta=-31.42; 95% CI=-37.86 to -24.98), learning (beta=-7.32; 95% CI=-9.23 to -5.41), teachers (beta=-5.37; 95% CI=-7.16 to -3.58), academic self-perception (beta=-7.33; 95% CI=-8.53 to -6.12), atmosphere (beta=-8.29; 95% CI=-10.13 to -6.44) and social self-perception (beta=-3.12; 95% CI=-4.11 to -2.12) DREEM domain scores. We also observed a dose-response pattern across resilience level groups for most measurements. Medical students with higher resilience levels had a better quality of life and a better perception of educational environment. Developing resilience may become an important strategy to minimize emotional distress and enhance medical training106CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPE

Wild dogs at stake: deforestation threatens the only Amazon endemic canid, the short-eared dog (Atelocynus microtis)

The persistent high deforestation rate and fragmentation of the Amazon forests are the main threats to their biodiversity. To anticipate and mitigate these threats, it is important to understand and predict how species respond to the rapidly changing landscape. The short-eared dog Atelocynus microtis is the only Amazon-endemic canid and one of the most understudied wild dogs worldwide. We investigated short-eared dog habitat associations on two spatial scales. First, we used the largest record database ever compiled for short-eared dogs in combination with species distribution models to map species habitat suitability, estimate its distribution range and predict shifts in species distribution in response to predicted deforestation across the entire Amazon (regional scale). Second, we used systematic camera trap surveys and occupancy models to investigate how forest cover and forest fragmentation affect the space use of this species in the Southern Brazilian Amazon (local scale). Species distribution models suggested that the short-eared dog potentially occurs over an extensive and continuous area, through most of the Amazon region south of the Amazon River. However, approximately 30% of the short-eared dog's current distribution is expected to be lost or suffer sharp declines in habitat suitability by 2027 (within three generations) due to forest loss. This proportion might reach 40% of the species distribution in unprotected areas and exceed 60% in some interfluves (i.e. portions of land separated by large rivers) of the Amazon basin. Our local-scale analysis indicated that the presence of forest positively affected short-eared dog space use, while the density of forest edges had a negative effect. Beyond shedding light on the ecology of the short-eared dog and refining its distribution range, our results stress that forest loss poses a serious threat to the conservation of the species in a short time frame. Hence, we propose a re-assessment of the short-eared dog's current IUCN Red List status (Near Threatened) based on findings presented here. Our study exemplifies how data can be integrated across sources and modelling procedures to improve our knowledge of relatively understudied species

Theory and Applications of Non-Relativistic and Relativistic Turbulent Reconnection

Realistic astrophysical environments are turbulent due to the extremely high Reynolds numbers. Therefore, the theories of reconnection intended for describing astrophysical reconnection should not ignore the effects of turbulence on magnetic reconnection. Turbulence is known to change the nature of many physical processes dramatically and in this review we claim that magnetic reconnection is not an exception. We stress that not only astrophysical turbulence is ubiquitous, but also magnetic reconnection itself induces turbulence. Thus turbulence must be accounted for in any realistic astrophysical reconnection setup. We argue that due to the similarities of MHD turbulence in relativistic and non-relativistic cases the theory of magnetic reconnection developed for the non-relativistic case can be extended to the relativistic case and we provide numerical simulations that support this conjecture. We also provide quantitative comparisons of the theoretical predictions and results of numerical experiments, including the situations when turbulent reconnection is self-driven, i.e. the turbulence in the system is generated by the reconnection process itself. We show how turbulent reconnection entails the violation of magnetic flux freezing, the conclusion that has really far reaching consequences for many realistically turbulent astrophysical environments. In addition, we consider observational testing of turbulent reconnection as well as numerous implications of the theory. The former includes the Sun and solar wind reconnection, while the latter include the process of reconnection diffusion induced by turbulent reconnection, the acceleration of energetic particles, bursts of turbulent reconnection related to black hole sources as well as gamma ray bursts. Finally, we explain why turbulent reconnection cannot be explained by turbulent resistivity or derived through the mean field approach.Comment: 66 pages, 24 figures, a chapter of the book "Magnetic Reconnection - Concepts and Applications", editors W. Gonzalez, E. N. Parke

Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial

Background Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression. Methods To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing. Results We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p = 0.04), and at D7 (p < 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen's d = 0.84; D2: Cohen's d = 0.84; D7: Cohen's d = 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% v. 27%; p = 0.04). Remission rate showed a trend toward significance at D7 (36% v. 7%, p = 0.054). Conclusions To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered at http://clinicaltrials.gov (NCT02914769)

Erratum to: The study of cardiovascular risk in adolescents – ERICA: rationale, design and sample characteristics of a national survey examining cardiovascular risk factor profile in Brazilian adolescents

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