Anti‐atherosclerotic effect of the angiotensin 1–7 mimetic AVE0991 is mediated by inhibition of perivascular and plaque inflammation in early atherosclerosis

Background and Purpose: Inflammation plays a key role in atherosclerosis. A protective role of angiotensin-(1-7) in vascular pathologies opened a possibility for therapeutic use of small molecule non-peptide Ang-(1-7) mimetics, such as AVE0991. The mechanisms of these vaso-protective effects of a Mas receptor agonist, AVE0991, remain unclear. Experimental approach: We investigated the effects of AVE0991 on the spontaneous atherosclerosis in ApoE-/- mice, in the context of vascular inflammation and plaque stability. Key Results: AVE0991 has significant anti-atherosclerotic properties in ApoE-/- mice and increases plaque stability, by reducing plaque macrophage content, without effects on collagen. Using descending aorta of chow fed ApoE-/- mice, before significant atherosclerotic plaque develops, we gained insight to early events in atherosclerosis. Interestingly, perivascular adipose tissue (pVAT) and adventitial infiltration with macrophages and T cells precedes atherosclerotic plaque or the impairment of endothelium-dependent NO bioavailability as a measure of endothelial function. AVE0991 inhibited perivascular inflammation, through the reduction of chemokine expression in pVAT, as well as through direct actions on monocytes/macrophages inhibiting their activation, characterized by IL-1β, TNF-α, MCP-1 and CXCL10 and differentiation to M1 phenotype. Pre-treatment with AVE0991 inhibited migration of THP-1 monocytes towards supernatants of activated adipocytes (SW872). Mas receptors were expressed in pVAT and in THP-1 cells in vitro and anti-inflammatory effects of AVE0991 were partially Mas dependent. Conclusions & implications: Selective Mas receptor agonist AVE0991 possesses anti-atherosclerotic and anti-inflammatory properties, affecting monocyte/macrophage differentiation and recruitment to perivascular space at early stages of atherosclerosis in ApoE-/- mice

Self-organized criticality in deterministic systems with disorder

Using the Bak-Sneppen model of biological evolution as our paradigm, we investigate in which cases noise can be substituted with a deterministic signal without destroying Self-Organized Criticality (SOC). If the deterministic signal is chaotic the universality class is preserved; some non-universal features, such as the threshold, depend on the time correlation of the signal. We also show that, if the signal introduced is periodic, SOC is preserved but in a different universality class, as long as the spectrum of frequencies is broad enough.Comment: RevTex, 8 pages, 8 figure

Glucose consumption rate-dependent transcriptome profiling of Escherichia coli provides insight on performance as microbial factories

peer reviewedBACKGROUND: The modification of glucose import capacity is an engineering strategy that has been shown to improve the characteristics of Escherichia coli as a microbial factory. A reduction in glucose import capacity can have a positive effect on production strain performance, however, this is not always the case. In this study, E. coli W3110 and a group of four isogenic derivative strains, harboring single or multiple deletions of genes encoding phosphoenolpyruvate:sugar phosphotransferase system (PTS)-dependent transporters as well as non-PTS transporters were characterized by determining their transcriptomic response to reduced glucose import capacity. RESULTS: These strains were grown in bioreactors with M9 mineral salts medium containing 20 g/L of glucose, where they displayed specific growth rates ranging from 0.67 to 0.27 h-1, and specific glucose consumption rates (qs) ranging from 1.78 to 0.37 g/g h. RNA-seq analysis revealed a transcriptional response consistent with carbon source limitation among all the mutant strains, involving functions related to transport and metabolism of alternate carbon sources and characterized by a decrease in genes encoding glycolytic enzymes and an increase in gluconeogenic functions. A total of 107 and 185 genes displayed positive and negative correlations with qs, respectively. Functions displaying positive correlation included energy generation, amino acid biosynthesis, and sugar import. CONCLUSION: Changes in gene expression of E. coli strains with impaired glucose import capacity could be correlated with qs values and this allowed an inference of the physiological state of each mutant. In strains with lower qs values, a gene expression pattern is consistent with energy limitation and entry into the stationary phase. This physiological state could explain why these strains display a lower capacity to produce recombinant protein, even when they show very low rates of acetate production. The comparison of the transcriptomes of the engineered strains employed as microbial factories is an effective approach for identifying favorable phenotypes with the potential to improve the synthesis of biotechnological products. © 2022. The Author(s)

The sensitivity of the vortex filament method to different reconnection models

We present a detailed analysis on the effect of using different algorithms to model the reconnection of vortices in quantum turbulence, using the thin-filament approach. We examine differences between four main algorithms for the case of turbulence driven by a counterflow. In calculating the velocity field we use both the local induction approximation (LIA) and the full Biot-Savart integral. We show that results of Biot-Savart simulations are not sensitive to the particular reconnection method used, but LIA results are.Comment: 9 pages, 9 figure

Tree method for quantum vortex dynamics

We present a numerical method to compute the evolution of vortex filaments in superfluid helium. The method is based on a tree algorithm which considerably speeds up the calculation of Biot-Savart integrals. We show that the computational cost scales as Nlog{(N) rather than N squared, where $N$ is the number of discretization points. We test the method and its properties for a variety of vortex configurations, ranging from simple vortex rings to a counterflow vortex tangle, and compare results against the Local Induction Approximation and the exact Biot-Savart law.Comment: 12 pages, 10 figure

In vitro assessment of antibiotic-resistance reversal of a methanol extract from Rosa canina L.

The crude methanol extract of Rosa canina (RC) fruit was tested against multidrug-resistant (MDR) bacterial strains, including methicillin-resistant Staphylococcus aureus SA1199B, EMRSA16 and XU212 harbouring NorA, PBP2a and TetK resistance mechanisms, respectively, as well as S. aureus ATCC25923, a standard antimicrobial susceptible laboratory strain. The inhibition of the conjugal transfer of plasmid PKM101 and TP114 by the RC extract was also evaluated. The RC extract demonstrated a mild to poor antibacterial activity against the panel of bacteria having MIC values ranging from 256 to >512 μg/mL but strongly potentiated tetracycline activity (64-fold) against XU212, a tetracycline-effluxing and resistant strain. Furthermore, the extract showed moderate capacity to inhibit the conjugal transfer of TP114 and PKM101; transfer frequencies were between 40% and 45%. Cytotoxicity analysis of the RC extract against HepG2 cells line showed the IC50 > 500 mg/L and, thus, was considered non-toxic towards human cells. Phytochemical characterisation of the extracts was performed by the assessment of total phenolic content (RC: 60.86 mg TAE/g) and HPLC fingerprints with five main peaks at 360 nm. The results from this study provide new mechanistic evidence justifying, at least in part, the traditional use of this extract. However, the inhibition of bacterial plasmid conjugation opens the possibility of combination therapies to overcome antibiotic resistance

Efeitos da quitosana no desenvolvimento in vitro de videiras cv. merlot e no crescimento micelial do fungo elsinoe ampelina.

Objetivou-se, neste trabalho, avaliar o efeito da quitosana no desenvolvimento in vitro de plântulas de videira cv. Merlot e sua atividade antifúngica sobre Elsinoe ampelina. No primeiro experimento, explantes da cultivar Merlot foram transferidos para meio de cultura DSD1, acrescido das concentrações 0; 25; 50,100; 150 e 200 mg L-1 de quitosana. Após 90 dias de cultivo in vitro, as plântulas foram avaliadas quanto ao número de raízes e de folhas, porcentagem de enraizamento e brotação, comprimento de raízes e de parte aérea, massa fresca da planta. No segundo experimento, incorporou-se às concentrações 0, 60, 120, 180, 240 e 300 mg L-1 de quitosana ao meio BDA, onde inoculou-se o fungo. Posteriormente, avaliou-se o crescimento micelial aos 6 e 9 dias de incubação a 25º C no escuro. No primeiro experimento para as variáveis comprimento médio da parte aérea, massa fresca da planta inteira, porcentagem de enraizamento e porcentagem de estacas brotadas houve decréscimo linear em função das concentrações de quitosana. No segundo experimento, houve efeito linear negativo em função das concentrações crescentes de quitosana, sendo que a inibição do crescimento micelial foi de 81,7%, demonstrando o grande potencial do uso de quitosana no controle da antracnose da videira

A solution scan of societal options to reduce transmission and spread of respiratory viruses: SARS-CoV-2 as a case study

Societal biosecurity – measures built into everyday society to minimize risks from pests and diseases – is an important aspect of managing epidemics and pandemics. We aimed to identify societal options for reducing the transmission and spread of respiratory viruses. We used SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) as a case study to meet the immediate need to manage the COVID-19 pandemic and eventually transition to more normal societal conditions, and to catalog options for managing similar pandemics in the future. We used a ‘solution scanning’ approach. We read the literature; consulted psychology, public health, medical, and solution scanning experts; crowd-sourced options using social media; and collated comments on a preprint. Here, we present a list of 519 possible measures to reduce SARS-CoV-2 transmission and spread. We provide a long list of options for policymakers and businesses to consider when designing biosecurity plans to combat SARS-CoV-2 and similar pathogens in the future. We also developed an online application to help with this process. We encourage testing of actions, documentation of outcomes, revisions to the current list, and the addition of further options.</p

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results