Experimental benznidazole treatment of Trypanosoma cruzi II strains isolated from children of the Jequitinhonha Valley,Minas Gerais,Brazil, with Chagas disease

Trypanosoma cruzi strains from distinct geographic areas show differences in drug resistance and association between parasites genetic and treatment response has been observed. Considering that benznidazole (BZ) can reduce the parasite burden and tissues damage, even in not cured animals and individuals, the goal is to assess the drug response to BZ of T. cruzi II strains isolated from children of the Jequitinhonha Valley, state of Minas Gerais, Brazil, before treatment. Mice infected and treated with BZ in both phases of infection were compared with the untreated and evaluated by fresh blood examination, haemoculture, polymerase chain reaction, conventional (ELISA) and non-conventional (FC-ALTA) serologies. In mice treated in the acute phase, a significant decrease in parasitaemia was observed for all strains. Positive parasitological and/or serological tests in animals treated during the acute and chronic (95.1-100%) phases showed that most of the strains were BZ resistant. However, beneficial effect was demonstrated because significant reduction (p < 0.05%) and/or suppression of parasitaemia was observed in mice infected with all strains (acute phase), associated to reduction/elimination of inflammation and fibrosis for two/eight strains. BZ offered some benefit, even in not cured animals, what suggest that BZ use may be recommended at least for recent chronic infection of the studied region.     

Controls of the quantum yield and saturation light of isoprene emission in different‐aged aspen leaves

Leaf age alters the balance between the use of end‐product of plastidic isoprenoid synthesis pathway, dimethylallyl diphosphate (DMADP), in prenyltransferase reactions leading to synthesis of pigments of photosynthetic machinery and in isoprene synthesis, but the implications of such changes on environmental responses of isoprene emission have not been studied. Because under light‐limited conditions, isoprene emission rate is controlled by DMADP pool size (S_DMADP), shifts in the share of different processes are expected to particularly strongly alter the light dependency of isoprene emission. We examined light responses of isoprene emission in young fully expanded, mature and old non‐senescent leaves of hybrid aspen (Populus tremula x P. tremuloides) and estimated in vivo S_DMADP and isoprene synthase activity from post‐illumination isoprene release. Isoprene emission capacity was 1.5‐fold larger in mature than in young and old leaves. The initial quantum yield of isoprene emission (α_I) increased by 2.5‐fold with increasing leaf age primarily as the result of increasing S_DMADP. The saturating light intensity (Q_I90) decreased by 2.3‐fold with increasing leaf age, and this mainly reflected limited light‐dependent increase of S_DMADP possibly due to feedback inhibition by DMADP. These major age‐dependent changes in the shape of the light response need consideration in modelling canopy isoprene emission.     

Evidence that vulture restaurants increase the local abundance of mammalian carnivores in South Africa

Vulture restaurants are used worldwide as a conservation tool to provide threatened vultures with a source of supplementary carrion free from anthropogenic contaminants such as poisons and veterinary drugs. While the impacts of supplementary feeding sites on ecosystem and scavenging community dynamics have been investigated in Europe, no information is currently available for southern Africa. This study presents evidence that providing supplementary carrion for vultures stimulated an increase in local abundance of two species of mammalian carnivores, the brown hyaena (Hyaena brunnea) and the black‐backed jackal (Canis mesomelas). These findings require that the wider impacts of providing supplementary carrion for conserving threatened species are fully investigated.     

Assembly of Slx4 signaling complexes behind DNA replication forks

Obstructions to replication fork progression, referred to collectively as DNA replication stress, challenge genome stability. In Saccharomyces cerevisiae, cells lacking RTT107 or SLX4 show genome instability and sensitivity to DNA replication stress and are defective in the completion of DNA replication during recovery from replication stress. We demonstrate that Slx4 is recruited to chromatin behind stressed replication forks, in a region that is spatially distinct from that occupied by the replication machinery. Slx4 complex formation is nucleated by Mec1 phosphorylation of histone H2A, which is recognized by the constitutive Slx4 binding partner Rtt107. Slx4 is essential for recruiting the Mec1 activator Dpb11 behind stressed replication forks, and Slx4 complexes are important for full activity of Mec1. We propose that Slx4 complexes promote robust checkpoint signaling by Mec1 by stably recruiting Dpb11 within a discrete domain behind the replication fork, during DNA replication stress.     

麦长管蚜对E-β-法尼烯的嗅觉行为反应

【目的】测定麦长管蚜Sitobion avenae Fabricius对E-β-法尼烯(E-β-farnesene,EβF)矿物油溶液反应的最低阈值浓度,为EβF的田间应用提供依据。【方法】观察麦长管蚜3龄若蚜对不同浓度EβF的逃逸行为和"Y"型管嗅觉行为反应。每天定时分5次(9:00,11:30,14:00,16:30和19:00)滴加10μL EβF于滤纸上,滤纸用牙签固定于麦苗盆中心,持续处理5 d。每盆麦苗处理前接1龄若蚜15头。记录成蚜翅型及2周后蚜虫总数量。【结果】随着EβF浓度升高,麦长管蚜3龄若蚜3 min内逃离数显著增加,有翅蚜比例显著增加,种群个体数量显著下降,驱避效果明显增强。EβF浓度为200 ng/μL和≥600 ng/μL使蚜虫逃离数显著增加(P0.05)。"Y"型管选择行为测试结果表明,EβF≥600 ng/μL对3龄若蚜具有极显著的驱避作用(P0.01)。与对照相比,EβF≥600 ng/μL处理极显著提高了有翅蚜比例(P0.01);EβF≥400 ng/μL极显著抑制蚜虫种群个体数量增长(P0.01),但与600 ng/μL处理差异不显著。【结论】600 ng/μL EβF矿物油溶液为麦长管蚜驱避剂的最低阈值浓度。     

Conformational dynamics of nonsynonymous variants at protein interfaces reveals disease association

Recent studies have shown that the protein interface sites between individual monomeric units in biological assemblies are enriched in disease‐associated non‐synonymous single nucleotide variants (nsSNVs). To elucidate the mechanistic underpinning of this observation, we investigated the conformational dynamic properties of protein interface sites through a site‐specific structural dynamic flexibility metric (dfi) for 333 multimeric protein assemblies. dfi measures the dynamic resilience of a single residue to perturbations that occurred in the rest of the protein structure and identifies sites contributing the most to functionally critical dynamics. Analysis of dfi profiles of over a thousand positions harboring variation revealed that amino acid residues at interfaces have lower average dfi (31%) than those present at non‐interfaces (50%), which means that protein interfaces have less dynamic flexibility. Interestingly, interface sites with disease‐associated nsSNVs have significantly lower average dfi (23%) as compared to those of neutral nsSNVs (42%), which directly relates structural dynamics to functional importance. We found that less conserved interface positions show much lower dfi for disease nsSNVs as compared to neutral nsSNVs. In this case, dfi is better as compared to the accessible surface area metric, which is based on the static protein structure. Overall, our proteome‐wide conformational dynamic analysis indicates that certain interface sites play a critical role in functionally related dynamics (i.e., those with low dfi values), therefore mutations at those sites are more likely to be associated with disease. Proteins 2015; 83:428–435. © 2014 Wiley Periodicals, Inc.     

In silico mutational studies of Hsp70 disclose sites with distinct functional attributes

The Mutation‐Minimization Method (MuMi) to study the local response of proteins to point mutations has been introduced here. The heat shock protein Hsp70 as the test system since it displays features that have been studied in great detail has been used here. It has many conserved residues, serves several different functions on each of its domains, and displays interdomain allostery. For the analysis of spatial arrangement of residues within the protein, the network properties of the wild type (WT) protein as well as its all single alanine residue mutants using MuMi has been investigated. The measures to express the amount of change from the WT structure upon mutation and compare these deviations to find potential critical sites have been proposed. The functional significance of the potential sites to the parameter that uncovers them has been mapped. It was found that sites directly involved in binding were sensitive to mutations and were characterized by large displacements. On the other hand, sites that steer large conformational changes typically had increased reachability upon alanine mutations occurring elsewhere in the protein. Finally, residues that control communication within and between domains reside on the largest number of paths connecting pairs of residues in the protein. Proteins 2015; 83:2077–2090. © 2015 Wiley Periodicals, Inc.     

Aldehyde-modified proteins as mediators of early inflammation in atherosclerotic disease

Inflammation is widely accepted to play a major role in atherosclerosis and other cardiovascular diseases. However, the exact mechanism(s) by which inflammation exerts its pathogenic effect remains poorly understood. A number of oxidatively modified proteins have been associated with cardiovascular disease. Recently, attention has been given to the oxidative compound of malondialdehyde and acetaldehyde, two reactive aldehydes known to covalently bind and adduct macromolecules. These products have been shown to form stable malondialdehyde–acetaldehyde (MAA) adducts that are reactive and induce immune responses. These adducts have been found in inflamed and diseased cardiovascular tissue of patients. Antibodies to these adducted proteins are measurable in the serum of diseased patients. The isotypes involved in the immune response to MAA (i.e., IgM, IgG, and IgA) are predictive of atherosclerotic disease progression and cardiovascular events such as an acute myocardial infarction or coronary artery bypass grafting. Therefore, it is the purpose of this article to review the past and current knowledge of aldehyde-modified proteins and their role in cardiovascular disease.     

Retinal damage induced by commercial light emitting diodes (LEDs)

Spectra of “white LEDs” are characterized by an intense emission in the blue region of the visible spectrum, absent in daylight spectra. This blue component and the high intensity of emission are the main sources of concern about the health risks of LEDs with respect to their toxicity to the eye and the retina. The aim of our study was to elucidate the role of blue light from LEDs in retinal damage. Commercially available white LEDs and four different blue LEDs (507, 473, 467, and 449 nm) were used for exposure experiments on Wistar rats. Immunohistochemical stain, transmission electron microscopy, and Western blot were used to exam the retinas. We evaluated LED-induced retinal cell damage by studying oxidative stress, stress response pathways, and the identification of cell death pathways. LED light caused a state of suffering of the retina with oxidative damage and retinal injury. We observed a loss of photoreceptors and the activation of caspase-independent apoptosis, necroptosis, and necrosis. A wavelength dependence of the effects was observed. Phototoxicity of LEDs on the retina is characterized by a strong damage of photoreceptors and by the induction of necrosis.