A Coarse-Grained Molecular Dynamics Approach to the Study of the Intrinsically Disordered Protein α-Synuclein.

Intrinsically disordered proteins (IDPs) are not well described by a single 3D conformation but by an ensemble of them, which makes their structural characterization especially challenging, both experimentally and computationally. Most all-atom force fields are designed for folded proteins and give too compact IDP conformations. α-Synuclein is a well-known IDP because of its relation to Parkinson's disease (PD).

Thermogenic capacity in subterranean Ctenomys: Species-specific role of thermogenic mechanisms.

One way to understand ecological patterns of species is to determine their physiological diversity on a large geographic and/or temporal scales, in a context of hierarchical biodiversity framework. In particular, macrophysiological studies analyze how environmental factors affect the physiology and therefore the distribution of species. Subterranean species are an excellent model for evaluating the large-scale effects of ambient temperature (T) conditions on thermal physiology and distribution, due to their extensive use of burrows that provide a relatively thermal stable environment.

Does glycation really distort the peptide α-helicity?

The understanding of the effect of non-enzymatic post-translational modifications on the protein structure is essential to unveil the molecular mechanisms underlying their related pathological processes. Among those modifications, protein glycation emerges as one of the main responsible for the development of diabetes-related diseases. While some reports suggest that glycation has a chaotropic effect, others indicate that it does not modify the protein structure.

Optimization and pharmacological characterization of receptor-mediated G activation in postmortem human prefrontal cortex.

The biochemical abnormalities in transmembrane signal transduction mediated through G protein-coupled receptors (GPCRs) have been postulated as underlying pathophysiology of psychiatric diseases such as schizophrenia and mood disorders. In the present study, the experimental conditions of agonist-induced [ S]GTPγS binding in postmortem human brain membranes were optimized, and the responses induced by a series of agonists were pharmacologically characterized. The [ S]GTPγS binding assay was performed in postmortem human prefrontal cortical membranes by means of filtration techniques, and standardized as to GDP concentration, membrane protein content, MgCl and NaCl concentrations in assay buffer, incubation period and effect of white matter contamination.

Analysis of 21 X-chromosome polymorphisms in urban and rural populations in Salta province (north-western Argentina).

Population genetic data for 21 X-chromosome markers (Alu insertions and STRs) are reported for two populations (rural and urban) in Salta province (north-western Argentina). New variants are described, confirming the complexity and variability of some markers in this set. Results reveal Salta populations harbor a high Native American component, despite their self-recognized European ancestry.

Pentobarbital and other anesthetic agents induce opposite regulations of MAP kinases p-MEK and p-ERK, and upregulate p-FADD/FADD neuroplastic index in brain during hypnotic states in mice.

Midazolam and ketamine-induced anesthesia were recently shown to induce a disruption of MEK/ERK sequential phosphorylation with parallel upregulation of p-FADD in the mouse brain. The present study was designed to assess whether other structurally diverse anesthetic agents (pentobarbital, ethanol, chloral hydrate, isoflurane) also impair brain p-MEK to p-ERK signal and increase p-FADD during the particular time course of 'sleep' in mice. Pentobarbital (50 mg/kg)-, ethanol (4000 mg/kg)-, chloral hydrate (400 mg/kg)-, and isoflurane (2% in O)-induced anesthesia (range: 24-60 min) were associated with unaltered or increased p-MEK1/2 (up to +155%) and decreased p-ERK1/2 (up to -60%) contents, revealing disruption of MEK to ERK activation in mouse brain cortex.

Plasma Acylcarnitines and Risk of Type 2 Diabetes in a Mediterranean Population at High Cardiovascular Risk.

Context: The potential associations between acylcarnitine profiles and incidence of type 2 diabetes (T2D) and whether acylcarnitines can be used to improve diabetes prediction remain unclear.

Objective: To evaluate the associations between baseline and 1-year changes in acylcarnitines and their diabetes predictive ability beyond traditional risk factors.

Design, Setting, And Participants: We designed a case-cohort study within the PREDIMED Study including all incident cases of T2D (n = 251) and 694 randomly selected participants at baseline (follow-up, 3.

GPER and ERα mediate estradiol enhancement of mitochondrial function in inflamed adipocytes through a PKA dependent mechanism.

Obesity is associated with inflammation, dysregulated adipokine secretion, and disrupted adipose tissue mitochondrial function. Estradiol (E2) has been previously reported to increase mitochondrial function and biogenesis in several cell lines, but neither the type of oestrogen receptor (ERα, ERβ and GPER) involved nor the mechanism whereby such effects are exerted have been fully described. Considering the anti-inflammatory activity of E2 as well as its effects in enhancing mitochondrial biogenesis, the aim of this study was to investigate the contribution of ERα, ERβ, and GPER signaling to the E2-mediated enhancement of adipocyte mitochondrial function in a pro-inflammatory situation.

Ketamine-induced hypnosis and neuroplasticity in mice is associated with disrupted p-MEK/p-ERK sequential activation and sustained upregulation of survival p-FADD in brain cortex: Involvement of GABA receptor.

Ketamine (KET) is an antidepressant and hypnotic drug acting as an antagonist at excitatory NMDA glutamate receptors. The working hypothesis postulated that KET-induced sleep in mice results in dysregulation of mitogen-activated protein kinases (MAPK) MEK-ERK sequential phosphorylation and upregulation of survival p-FADD and other neuroplastic markers in brain. Low (5-15 mg/kg) and high (150 mg/kg) doses of KET on target proteins were assessed by Western immunoblot in mouse brain cortex.

Facilitators and barriers to modifying dietary and hygiene behaviours as adjuvant treatment in patients with depression in primary care: a qualitative study.

Background: Major depression is a highly prevalent condition. Its pathogenesis is related to a wide variety of biological and psychosocial factors and among these is factors related to lifestyle. Lifestyle-based interventions seem to be appropriate strategies as coadjutant treatment.

An internet-based intervention for adjustment disorder (TAO): study protocol for a randomized controlled trial.

Background: Adjustment Disorder (AjD) is a common and disabling mental health problem. The lack of research on this disorder has led to the absence of evidence-based interventions for its treatment. Moreover, because the available data indicate that a high percentage of people with mental illness are not treated, it is necessary to develop new ways to provide psychological assistance.

The association between depression and eating styles in four European countries: The MooDFOOD prevention study.

Objective: Depression, one of the most prevalent and disabling disorders in Europe, is thought to be associated with unhealthy eating styles. As prevalence of depression and eating styles potentially differ across Europe, the current study aimed to investigate in a large, European sample, the associations of history of major depressive disorder and depression severity with unhealthy eating styles.

Methods: Baseline data of the MooDFOOD prevention study was used.

Genetic portrait of Jewish populations based on three sets of X-chromosome markers: Indels, Alu insertions and STRs.

Population genetic data for 53 X-chromosome markers (32 X-indels, 9 X-Alu insertions and 12 X-STRs) are reported for five populations with Jewish ancestry (Sephardim, North African Jews, Middle Eastern Jews, Ashkenazim, and Chuetas) and Majorca, as the host population of Chuetas. Genetic distances between these populations demonstrated significant differences, except between Sephardic and North African Jews, with the Chuetas as the most differentiated group, in accordance with the particular demographic history of this population. X-chromosome analysis and a comparison with autosomal data suggest a generally sex-biased demographic history in Jewish populations.

Copper(II) Binding Sites in N-Terminally Acetylated α-Synuclein: A Theoretical Rationalization.

The interactions between N-terminally acetylated α-synuclein and Cu(II) at several binding sites have been studied with DFT calculations, specifically with the M06 hybrid functional and the ωB97X-D DFT-D functional. In previous experimental studies, Cu(II) was shown to bind several α-synuclein residues, including Met1-Asp2 and His50, forming square planar coordination complexes. Also, it was determined that a low-affinity binding site exists in the C-terminal domain, centered on Asp121.

New insights into human farnesyl pyrophosphate synthase inhibition by second-generation bisphosphonate drugs.

Pamidronate, alendronate, APHBP and neridronate are a group of drugs, known as second-generation bisphosphonates (2G-BPs), commonly used in the treatment of bone-resorption disorders, and recently their use has been related to some collateral side effects. The therapeutic activity of 2G-BPs is related to the inhibition of the human Farnesyl Pyrophosphate Synthase (hFPPS). Available inhibitory activity values show that 2G-BPs act time-dependently, showing big differences in their initial inhibitory activities but similar final IC values.

INDUCTION OF CELL CYCLE ARREST AND APOPTOSIS BY ORMENIS ERIOLEPIS A MORROCAN ENDEMIC PLANT IN VARIOUS HUMAN CANCER CELL LINES.

Background: (Asteraceae) is an endemic Moroccan subspecies, traditionally named "Hellala" or "Fergoga". It's usually used for its hypoglycemic effect as well as for the treatment of stomacal pain. As far as we know, there is no scientific exploration of anti tumoral activity of extracts.

Forensic efficiency parameters of the Investigator Argus X-12 kit in women from two Mestizo and seven Amerindian populations from Mexico.

Allele frequency distribution and statistical parameters of forensic efficiency concerning the Investigator Argus X-12 kit (Qiagen, Hilden, Germany) were determined in a total sample of 641 unrelated Mexican females, including two Mestizo-admixed- populations (n=309) and seven Amerindian groups (n=332) from the main regions of the country. Most of the 12 X-STRs were in agreement with Hardy-Weinberg expectations in all nine Mexican populations. The power of discrimination in females (PD) and Median exclusion chance for trios (MEC) and duos (MEC) of this genetic system based on X-STRs were >99.

Antioxidant peroxiredoxin 3 expression is regulated by 17beta-estradiol in rat white adipose tissue.

Peroxiredoxin 3 (PRX3) plays a role as a regulator of the adipocyte mitochondrial function due to its antioxidant activity. We have previously reported the existence of a sexual dimorphism in the mitochondrial oxidative stress status of many rat tissues such as white (WAT) and brown (BAT) adipose tissues. The aim was to elucidate whether sex hormones may play a role in PRX3 expression in the adipose tissues of rats.

Effectiveness of Psychological and Educational Interventions to Prevent Depression in Primary Care: A Systematic Review and Meta-Analysis.

Purpose: Although evidence exists for the efficacy of psychosocial interventions to prevent the onset of depression, little is known about its prevention in primary care. We aimed to evaluate the effectiveness of psychological and educational interventions to prevent depression in primary care.

Methods: We conducted a systematic review and meta-analysis of relevant randomized controlled trials (RCTs) examining the effect of psychological and educational interventions to prevent depression in nondepressed primary care attendees.

PGC-1α in Melanoma: A Key Factor for Antioxidant Response and Mitochondrial Function.

Melanocortin 1 receptor (MC1R) and BRAF are common mutations in melanoma. Through different pathways, they each regulate the expression of PGC-1α, which is a key factor in the regulation of mitochondrial biogenesis and the antioxidant response. Our aim was to study the importance of the different regulatory characteristics of MC1R and BRAF on the pathways they regulate in melanoma.