The N terminus of the peroxisomal cycling receptor, Pex5p, is required for redirecting the peroxisome-associated peroxin back to the cytosol

Most newly synthesized peroxisomal matrix proteins are transported to the organelle by Pex5p, a remarkable multidomain protein involved in an intricate network of transient protein-protein interactions. Presently, our knowledge regarding the structure/function of amino acid residues 118 to the very last residue of mammalian Pex5p is quite vast. Indeed, the cargo-protein receptor domain as well as the binding sites for several peroxins have all been mapped to this region of Pex5p. In contrast, structural/functional data regarding the first 117 amino acid residues of Pex5p are still scarce. Here we show that a truncated Pex5p lacking the first 110 amino acid residues (DeltaN110-Pex5p) displays exactly the peroxisomal import properties of the full-length peroxin implying that this N-terminal domain is involved neither in cargo-protein binding nor in the docking/translocation step of the Pex5p-cargo protein complex at the peroxisomal membrane. However, the ATP-dependent export step of DeltaN110-Pex5p from the peroxisomal membrane is completely blocked, a phenomenon that was also observed for a Pex5p version lacking just the first 17 amino acid residues but not for a truncated protein comprising amino acid residues 1-324 of Pex5p. By exploring the unique properties of DeltaN110-Pex5p, the effect of temperature on the import/export kinetics of Pex5p was characterized. Our data indicate that the export step of Pex5p from the peroxisomal compartment ( in contrast with its insertion into the organelle membrane) is highly dependent on the temperature

Ybp1 and Gpx3 signaling in Candida albicans govern hydrogen peroxide-induced oxidation of the Cap1 transcription factor and macrophage escape

Peer reviewedPublisher PD

Influencia de las actividades en la calidad de vida de los ancianos: revisión sistemática

Objetivo. Identificar quais as atividades ou intervenções que causan alterações na qualidade de vida dos idosos. Método. Revisão sistemática da literatura nas bases de dados: Scopus, ISI Web of Science, Scielo, Lilacs, BDENF e PubMed. O descritor principal do Medical Subject Heading (MeSH) utilizado foi “quality of life”, combinado com os termos de maior interesse "aged, motor activity, educatuion". A pesquisa foi realizada entre julho e agosto de 2015, e incluídos artigos originais publicados entre 2010 e 2015 em inglês, português e espanhol. Além disso foi seguida a estratégia da Cochrane para elaboração do revisão. Resultados. Foram estudados 27 artigos comparando a qualidade de vida dos idosos antes e após uma intervenção de tipo física, educacional ou mista. O principal resultado obtido são que os dominios estado geral de saúde, capacidade funcional, aspectos sociais, aspecto físico e satisfação com a vida apresentaram-se mais alterados, sendo as atividades físicas em grupo aquelas executadas en maior número. Conclusões. Concluiu-se que as atividades de qualquer espécie, de preferência adaptadas, causam mudanças na qualidade de vida dos idosos em termos gerais, com destaque para a melhora nos aspectos funcionais, mentais e sociais

Isolated Taylor Bubbles in Co-Current with Shear Thinning CMC Solutions in Microchannels—A Numerical Study

Slug flow is a multiphase flow pattern characterized by the occurrence of long gas bubbles (Taylor bubbles) separated by liquid slugs. This multiphase flow regime is present in many and diversified natural and industrial processes, at macro and microscales, such as in eruption of volcanic magmas, oil recovery from pre-salt regions, micro heat exchangers, and small-sized refrigerating systems. Previous studies in the literature have been mostly focused on tubular gas bubbles flowing in Newtonian liquids. In this work, results from several numerical simulations of tubular gas bubbles flowing in a shear thinning liquid in microchannels are reported. To simulate the shear thinning behavior, carboxymethylcellulose (CMC) solutions with different concentrations were considered. The results are compared with data from bubbles flowing in Newtonian liquids in identical geometric and dynamic conditions. The numerical work was carried out in computational fluid dynamics (CFD) package Ansys Fluent (release 16.2.0) employing the volume of fluid (VOF) methodology to track the volume fraction of each phase and the continuum surface force (CSF) model to insert the surface tension effects. The flow patterns, the viscosity distribution in the liquid, the liquid film thickness between the bubble and the wall, and the bubbles shape are analyzed for a wide range of shear rates. In general, the flow patterns are similar to those in Newtonian liquids, but in the film, where a high viscosity region is observed, the thickness is smaller. Bubble velocities are smaller for the non-Newtonian cases.</jats:p

The Importance of N186 in the Alpha-1-Antitrypsin Shutter Region Is Revealed by the Novel Bologna Deficiency Variant

Alpha-1-antitrypsin (AAT) deficiency causes pulmonary disease due to decreased levels of circulating AAT and consequently unbalanced protease activity in the lungs. Deposition of specific AAT variants, such as the common Z AAT, within hepatocytes may also result in liver disease. These deposits are comprised of ordered polymers of AAT formed by an inter-molecular domain swap. The discovery and characterization of rare variants of AAT and other serpins have historically played a crucial role in the dissection of the structural mechanisms leading to AAT polymer formation. Here, we report a severely deficient shutter region variant, Bologna AAT (N186Y), which was identified in five unrelated subjects with different geographical origins. We characterized the new variant by expression in cellular models in comparison with known polymerogenic AAT variants. Bologna AAT showed secretion deficiency and intracellular accumulation as detergent-insoluble polymers. Extracellular polymers were detected in both the culture media of cells expressing Bologna AAT and in the plasma of a patient homozygous for this variant. Structural modelling revealed that the mutation disrupts the hydrogen bonding network in the AAT shutter region. These data support a crucial coordinating role for asparagine 186 and the importance of this network in promoting formation of the native structure

Urinary tract infections under 24 months old: Is it possible to predict the risk of renal scarring?

Background: Urinary tract infection is one of the most common bacterial infections in the first two years of life and it can lead to irreversible renal scarring. Renal scintigraphy is the gold standard method for detection of renal scars. The aim of our work was to revise the cases of pyelonephritis, detect the possible predictors for renal scarring and compare those results we would have obtained if we had followed current NICE guidelines. Methods: Retrospective analysis of all patients aged under 24 months evaluated in the paediatric department and diag- nosed with pyelonephritis during a three -year period. We excluded the cases in which no renal scintigraphy was performed. Results: Of the 59 children analysed, 50.8% were boys and 86.4% were under one -year old. Escherichia coli was the predominant bacteria. Renal ultrasonography showed abnormal findings in 23 patients (39%). The incidence of renal scarring was 15.3%. Age, atypical urinary tract infection and abnormal renal ultrasonography seem to be correlated with risk of renal scarring, although the results were not statistically significant. C -reactive protein level is significantly correlated with renal scarring risk (p=0.047). Working outside the NICE guidelines allowed us to catch 7 further renal scars. Conclusions: It’s arguable if renal scintigraphy must be performed in all cases of pyelonephritis diagnosed in the first 24 months of life or only when there are other risk factors for renal scarring. Age, atypical urinary tract infection, C -reactive protein level and renal ultrasonography results must be taken into account in the decision to perform renal scintigraphy in a child. More prospective studies with larger cohorts are needed.info:eu-repo/semantics/publishedVersio

Associations between reliable changes in depression and changes in BMI, total body fatness and visceral adiposity during a 12-month weight loss trial.

We investigated associations between changes in depression and body composition over a 12-month weight loss trial. Of the 298 adults (BMI &gt; 27 m/kg2), 219 with complete depression and body composition data were included. A 10-item Center for Epidemiologic Studies Depression Scale measured depression; dual-energy X-ray absorptiometry measured body composition. Multinomial logistic regression predicted reliable changes in depression by BMI, body fat (BF) and visceral adiposity (VAT). Multiplicative interaction terms tested modification by sex and ethnicity. Participants with increases in body composition were less likely to experience improvements in depression (BMI: RRR = 0.79 (0.68-0.91), p &lt; 0.01; BF: RRR = 0.97 (0.94 - 0.99), p = 0.01; VAT: RRR = 0.99 (0.98-1.00), p = 0.02), but not worsening of depression (BMI: RRR = 1.29 (0.96-1.73), p = 0.10; BF: RRR = 1.04 (0.99-1.09), p = 0.15; VAT: RRR = 1.01 (1.00-1.03), p = 0.18). Sex and ethnicity interaction terms were not significant. However, the relationship was only significant among females, among non-Latinos for BMI and BF, and among Latinos for VAT. Our study supports the association between depression and obesity and highlights the need for longitudinal studies investigating VAT and depression in diverse ethnic groups

Effects of APOE4 allelic dosage on lipidomic signatures in the entorhinal cortex of aged mice

Apolipoprotein E ε4 (APOE4) is the primary genetic risk factor for the late-onset form of Alzheimer's disease (AD). Although the reason for this association is not completely understood, researchers have uncovered numerous effects of APOE4 expression on AD-relevant brain processes, including amyloid beta (Aβ) accumulation, lipid metabolism, endosomal-lysosomal trafficking, and bioenergetics. In this study, we aimed to determine the effect of APOE4 allelic dosage on regional brain lipid composition in aged mice, as well as in cultured neurons. We performed a targeted lipidomic analysis on an AD-vulnerable brain region (entorhinal cortex; EC) and an AD-resistant brain region (primary visual cortex; PVC) from 14-15 month-old APOE3/3, APOE3/4, and APOE4/4 targeted replacement mice, as well as on neurons cultured with conditioned media from APOE3/3 or APOE4/4 astrocytes. Our results reveal that the EC possesses increased susceptibility to APOE4-associated lipid alterations compared to the PVC. In the EC, APOE4 expression showed a dominant effect in decreasing diacylglycerol (DAG) levels, and a semi-dominant, additive effect in the upregulation of multiple ceramide, glycosylated sphingolipid, and bis(monoacylglycerol)phosphate (BMP) species, lipids known to accumulate as a result of endosomal-lysosomal dysfunction. Neurons treated with conditioned media from APOE4/4 vs. APOE3/3 astrocytes showed similar alterations of DAG and BMP species to those observed in the mouse EC. Our results suggest that APOE4 expression differentially modulates regional neuronal lipid signatures, which may underlie the increased susceptibility of EC-localized neurons to AD pathology