Candida albicans Hyphal Extracellular Vesicles Are Different from Yeast Ones, Carrying an Active Proteasome Complex and Showing a Different Role in Host Immune Response.

Candida albicans is the principal causative agent of lethal fungal infections, predominantly in immunocompromised hosts. Extracellular vesicles (EVs) have been described as crucial in the interaction of microorganisms with their host. Since the yeast-to-hypha transition is an important virulence trait with great impact in invasive candidiasis (IC), we have addressed the characterization of EVs secreted by hyphal cells (HEVs) from C. albicans, comparing them to yeast EVs (YEVs). YEVs comprised a larger population of bigger EVs with mainly cell wall proteins, while HEVs were smaller, in general, and had a much higher protein diversity. YEVs were able to rescue the sensitivity of a cell wall mutant against calcofluor white, presumably due to the larger amount of cell wall proteins they contained. On the other hand, HEVs also contained many cytoplasmic proteins related to protein metabolism and intracellular protein transport and the endosomal sorting complexes required for transport (ESCRT) pathway related to exosome biogenesis, pointing to an intracellular origin of HEVs. Interestingly, an active 20S proteasome complex was secreted exclusively in HEVs. Moreover, HEVs contained a greater number of virulence-related proteins. As for their immunogenic role, both types of EV presented immune reactivity with human sera from patients suffering invasive candidiasis; however, under our conditions, only HEVs showed a cytotoxic effect on human macrophages and could elicit the release of tumor necrosis factor alpha (TNF-α) by these macrophages. IMPORTANCE This first analysis of HEVs of C. albicans has shown clear differences between them and the YEVs of C. albicans, showing their relevance and possible use in the discovery of new diagnostic markers and treatment targets against C. albicans infections. The data obtained point to different mechanisms of biogenesis of YEVs and HEVs, as well as different involvements in cell biology and host interaction. YEVs played a more relevant role in cell wall maintenance, while HEVs were more closely related to virulence, as they had greater effects on human immune cells. Importantly, an active 20S proteosome complex was described as a fungal-EV cargo. A deeper study of its role and those of many other proteins exclusively detected in HEVs and involved in different relevant biological processes of this fungus could open up interesting new areas of research in the battle against C. albicans

Handgrip and knee extension strength as predictors of cancer mortality: A systematic review and metaâ analysis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145272/1/sms13206.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145272/2/sms13206_am.pd

The first Hochschild cohomology group of a schurian cluster-tilted algebra

Given a cluster-tilted algebra B we study its first Hochschild cohomology group HH1(B) with coefficients in the B-B-bimodule B. We find several consequences when B is representation-finite, and also in the case where B is cluster-tilted of type Ã.Fil: Assem, Ibrahim. University of Sherbrooke; CanadáFil: Redondo, Maria Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Matemática Bahía Blanca. Universidad Nacional del Sur. Departamento de Matemática. Instituto de Matemática Bahía Blanca; Argentin

Toll-like receptor 4 contributes to vascular remodelling and endothelial dysfunction in angiotensin II-induced hypertension

This is the peer-reviewed version of the following article: "Toll-like receptor 4 contributes to vascular remodelling and endothelial dysfunction in angiotensin II-induced hypertension", British Journal of Pharmacology 172.12 (2015): 3159-76 which has been published in final form at http://dx.doi.org/10.1111/bph.13117 This article may be used for non-commercial purposes in accordance with Wiley-VCH Terms and Conditions for Self-ArchivingBackground and Purpose Toll-like receptor 4 (TLR4) signalling contributes to inflammatory cardiovascular diseases, but its role in hypertension and the associated vascular damage is not known. We investigated whether TLR4 activation contributed to angiotensin II (AngII)-induced hypertension and the associated vascular structural, mechanical and functional alterations. Experimental Approach AngII was infused (1.44 mg·kg−1·day−1, s.c.) for 2 weeks in C57BL6 mice, treated with a neutralizing anti-TLR4 antibody or IgG (1 μg·day−1); systolic BP (SBP) and aortic cytokine levels were measured. Structural, mechanical and contractile properties of aortic and mesenteric arterial segments were measured with myography and histology. RT-PCR and Western blotting were used to analyse these tissues and cultured vascular smooth muscle cells (VSMC) from hypertensive rats (SHR). Key Results Aortic TLR4 mRNA levels were raised by AngII infusion. Anti-TLR4 antibody treatment of AngII-treated mice normalised: (i) increased SBP and TNF-α, IL-6 and CCL2 levels; (ii) vascular structural and mechanical changes; (iii) altered aortic phenylephrine- and ACh-induced responses; (iv) increased NOX-1 mRNA levels, superoxide anion production and NAD(P)H oxidase activity and effects of catalase, apocynin, ML-171 and Mito-TEMPO on vascular responses; and (v) reduced NO release and effects of L-NAME on phenylephrine-induced contraction. In VSMC, the MyD88 inhibitor ST-2825 reduced AngII-induced NAD(P)H oxidase activity. The TLR4 inhibitor CLI-095 reduced AngII-induced increased phospho-JNK1/2 and p65 NF-κB subunit nuclear protein expression. Conclusions and Implications TLR4 up-regulation by AngII contributed to the inflammation, endothelial dysfunction, vascular remodelling and stiffness associated with hypertension by mechanisms involving oxidative stress. MyD88-dependent activation and JNK/NF-κB signalling pathways participated in these alterationsThis work was supported by Ministerio de Economía y Competitividad (SAF2012-36400), Instituto de Salud Carlos III (Red de Investigación Cardiovascular RD12/0042/0024 and RD12/0042/0033) and URJC (PRIN13_CS12). AMB was supported by the Ramón y Cajal Program (RYC-2010-06473)

The Intrinsic Fundamental Group of a Linear Category

We provide an intrinsic definition of the fundamental group of a linear category over a ring as the automorphism group of the fibre functor on Galois coverings. If the universal covering exists, we prove that this group is isomorphic to the Galois group of the universal covering. The grading deduced from a Galois covering enables us to describe the canonical monomorphism from its automorphism group to the first Hochschild-Mitchell cohomology vector space.Comment: Final version, to appear in Algebras and Representation Theor

Deficiencia de vitamina D en niños aragoneses sanos

Introducción: la principal acción de la vitamina D es mantener la concentración de calcio y fósforo dentro del rango fisiológico permitiendo el metabolismo normal y la mineralización ósea. Últimamente, se han descrito receptores de vitamina D en muchos tejidos y se ha relacionado la deficiencia de la vitamina D no solo con raquitismo y osteomalacia, sino también con mayor riesgo de diabetes, obesidad, enfermedades cardiovasculares, oncológicas, infecciosas y autoinmunes. Objetivo: el objetivo del estudio fue conocer la concentración de vitamina D en una población pediátrica sana y comprobar sus factores influyentes, así como analizar la situación actual de profilaxis de vitamina D y valorar la eficacia de las recomendaciones actuales. Métodos: se seleccionaron 107 pacientes sanos, de edades comprendidas entre uno y 15 años, que precisaron una analítica sanguínea como preoperatorio de cirugía menor, cuya patología no influyera en los parámetros del estudio. Resultados: la muestra estaba constituida en un 78, 5% por varones y presentaba una media de edad de 7, 17 ± 3, 79 años. La concentración media de vitamina D fue de 26, 07 ± 7, 11 ng/ml y hasta un 72, 9% presentaba niveles insuficientes. Se dividió la muestra en dos grupos: pacientes con hipovitaminosis D y pacientes con niveles óptimos de vitamina D. Se observó en el grupo con hipovitaminosis un predominio de varones, mayor índice de masa corporal y la presencia de fototipos extremos así como provenientes de padres inmigrantes. También presentaban mayor riesgo de hipovitaminosis los que no habían realizado profilaxis durante el primer año de vida. Conclusiones: se pone de manifiesto el alto porcentaje de población infantil sana con déficit de vitamina D y que las recomendaciones actuales de profilaxis no son llevadas a cabo por la población como recomiendan las guías actuales Background: the main action of vitamin D is to maintain the concentration of calcium and phosphorus within the physiological range, allowing normal metabolism and bone mineralization. Vitamin D receptors have recently been described in many tissues, therefore vitamin D deficiency has been related not only to rickets, but also to increased risk of diabetes, obesity, cardiovascular, oncological, infectious and autoimmune diseases. Objective: the aim of the study was to know the vitamin D concentration in a healthy pediatric population and to verify its influential factors, as well as to analyze the current situation of vitamin D prophylaxis and to evaluate the effectiveness of current recommendations. Methods: one hundred and seven healthy patients aged between one and 15 years were selected, who required a blood test as a preoperative minor surgery and whose pathology did not influence the parameters of the study. Results: the sample analyzed had a total of 78.5% males and a mean age of 7.17 ± 3.79 years. Mean values of vitamin D were 26.07 ± 7.11 ng/ml; up to 72.9% had insufficient levels. The sample was divided into two groups: patients with hypovitaminosis D and patients with optimal vitamin D levels. A predominance of males with a higher body mass index, from immigrant parents, and the presence of extreme phototypes were observed in the hypovitaminosis group. There was also a higher risk of hypovitaminosis in those who had not performed prophylaxis during the first year of life. Conclusions: the high percentage of healthy children with vitamin D deficiency is evident, and current recommendations for prophylaxis are not carried out by the population as recommended by current guidelines

Field scale biodegradation of total petroleum hydrocarbons and soil restoration by Ecopiles: microbiological analysis of the process

Ecopiling is a method for biodegradation of hydrocarbons in soils. It derives from Biopiles, but phytoremediation is added to biostimulation with nitrogen fertilization and bioaugmentation with local bacteria. We have constructed seven Ecopiles with soil heavily polluted with hydrocarbons in Carlow (Ireland). The aim of the study was to analyze changes in the microbial community during ecopiling. In the course of 18 months of remediation, total petroleum hydrocarbons values decreased in 99 and 88% on average for aliphatics and aromatics, respectively, indicating a successful biodegradation. Community analysis showed that bacterial alfa diversity (Shannon Index), increased with the degradation of hydrocarbons, starting at an average value of 7.59 and ending at an average value of 9.38. Beta-diversity analysis, was performed using Bray-Curtis distances and PCoA ordination, where the two first principal components (PCs) explain the 17 and 14% of the observed variance, respectively. The results show that samples tend to cluster by sampling time instead of by Ecopile. This pattern is supported by the hierarchical clustering analysis, where most samples from the same timepoint clustered together. We used DSeq2 to determine the differential abundance of bacterial populations in Ecopiles at the beginning and the end of the treatment. While TPHs degraders are more abundant at the start of the experiment, these populations are substituted by bacterial populations typical of clean soils by the end of the biodegradation process. Similar results are found for the fungal community, indicating that the microbial community follows a succession along the process. This succession starts with a TPH degraders or tolerant enriched community, and finish with a microbial community typical of clean soil

Birth weight and blood lipid levels in Spanish adolescents: Influence of selected APOE, APOC3 and PPARgamma2 gene polymorphisms. The AVENA Study

Es reproducción del documento publicado en http://dx.doi.org/10.1186/1471-2350-9-98Background: There is increasing evidence indicating that genes involved in certain metabolic processes of cardiovascular diseases may be of particular influence in people with low body weight at birth. We examined whether the apolipoprotein (APO) E, APOC3 and the peroxisome proliferator-activated receptor-gamma-2 (PPAR gamma 2) polymorphisms influence the association between low birth weight and blood lipid levels in healthy adolescents aged 13-18.5 years. Methods: A cross-sectional study of 502 Spanish adolescents born at term was conducted. Total (TC) and high density lipoprotein cholesterol (HDLc), triglycerides (TG), apolipoprotein (apo) A and B, and lipoprotein(a) [ Lp(a)] were measured. Low density lipoprotein cholesterol (LDLc), TC-HDLc, TC/HDLc and apoB/apoA were calculated. Results: Low birth weight was associated with higher levels of TC, LDLc, apoB, Lp(a), TC-HDLc, TC/HDLc and apoB/apoA in males with the APOE epsilon 3 epsilon 4 genotype, whereas in females, it was associated with lower HDLc and higher TG levels. In males with the APOC3 S1/S2 genotype, low birth weight was associated with lower apoA and higher Lp(a), yet this association was not observed in females. There were no associations between low birth weight and blood lipids in any of the PPAR gamma 2 genotypes. Conclusion: The results indicate that low birth weight has a deleterious influence on lipid profile particularly in adolescents with the APOE epsilon 3/epsilon 4 genotype. These findings suggest that intrauterine environment interact with the genetic background affecting the lipid profile in later life.Instituto de Salud Carlos III (FIS PI021830), the Spanish Ministry of Health, FEDER-FSE funds FIS n 00/0015, CSD grants 05/UPB32/0, 109/UPB31/03 and 13/UPB20/04, Ministerio de Educación (AP-2004-2745; EX2007-1124

Activation-induced cytidine deaminase targets SUV4-20-mediated histone H4K20 trimethylation to class-switch recombination sites

Activation-induced cytidine deaminase (AID) triggers antibody diversification in B cells by catalysing deamination and subsequently mutating immunoglobulin (Ig) genes. Association of AID with RNA Pol II and occurrence of epigenetic changes during Ig gene diversification suggest participation of AID in epigenetic regulation. AID is mutated in hyper-IgM type 2 (HIGM2) syndrome. Here, we investigated the potential role of AID in the acquisition of epigenetic changes. We discovered that AID binding to the IgH locus promotes an increase in H4K20me3. In 293F cells, we demonstrate interaction between co-transfected AID and the three SUV4-20 histone H4K20 methyltransferases, and that SUV4-20H1.2, bound to the IgH switch (S) mu site, is replaced by SUV4-20H2 upon AID binding. Analysis of HIGM2 mutants shows that the AID truncated form W68X is impaired to interact with SUV4-20H1.2 and SUV4-20H2 and is unable to bind and target H4K20me3 to the Smu site. We finally show in mouse primary B cells undergoing class-switch recombination (CSR) that AID deficiency associates with decreased H4K20me3 levels at the Smu site. Our results provide a novel link between SUV4-20 enzymes and CSR and offer a new aspect of the interplay between AID and histone modifications in setting the epigenetic status of CSR sites