Monoamine oxidase A (MAOA) interaction with parenting practices on callous-unemotional traits in preschoolers

Background and Objectives: From a gene-by-environment perspective, parenting in interaction with the polymorphism in the Monoamine oxidase A (MAOA) gene (MAOA-uVNTR) might also be associated with increased callous-unemotional traits (CU) in preschoolers. MAOA-uVNTR results in differential enzyme activity, so that high-activity alleles (MAOA-H) are linked to reduced dopamine, serotonin, and norepinephrine availability in comparison to low-activity allele (MAOA-L). As MAOA-uVNTR has been previously described to moderate the relationship between childhood parental maltreatment and aggressive and antisocial behavior, it may also play a role in CU traits etiology

Seasonal and dietary influences on adipose tissue and systemic gene expression in control and previously laminitic ponies

The aims of the study were to determine whether adipose tissue global gene expression (i) differs between never laminitic (NL) and previously laminitic (PL) ponies; (ii) is influenced by season and/or a diet designed to simulate spring grass and (iii) differences seen also occur systemically in peripheral blood mononuclear cells (PBMCs). Subcutaneous adipose tissue and PBMCs were obtained from six NL and six PL ponies on three occasions; summer, winter (season study) and in winter after consuming a diet simulating spring grass for seven days (diet study). Adipose tissue global gene expression was determined using a 44K equine specific microarray, validated using multiplex quantitative real time PCR (qRT-PCR) and analysed using GeneSpring software and Ingenuity Pathway Analysis. PBMC gene expression was quantified using qRT-PCR. The total number of genes whose expression differed (=2-fold change, p=0.01) between PL and NL ponies was greater in summer (192 genes) compared to winter (58 genes); 40/192 genes influenced by disease in the summer were also seasonally regulated and were predominantly associated with inflammation. The genes modified by dietary intervention and PBMC gene expression did not follow the same pattern as the season study. Thus, adipose tissue global gene expression differed between NL and PL ponies most in summer compared to winter, and these differentially expressed genes predominantly related to inflammation

Are shallow-water shrimps proxies for hydrothermal-vent shrimps to assess the impact of deep-sea mining?

Polymetallic seafloor massive sulphide deposits are potential targets for deep-sea mining, but high concentrations of metals (including copper - Cu) may be released during exploitation activities, potentially inducing harmful impact. To determine whether shallow-water shrimp are suitable ecotoxicological proxies for deep-sea hydrothermal vent shrimp the effects of waterborne Cu exposure (3 and 10 days at 0.4 and 4 μM concentrations) in Palaemon elegans, Palaemon serratus, and Palaemon varians were compared with Mirocaris fortunata. Accumulation of Cu and a set of biomarkers were analysed. Results show different responses among congeneric species indicating that it is not appropriate to use shallow-water shrimps as ecotoxicological proxies for deep-water shrimps. During the evolutionary history of these species they were likely subject to different chemical environments which may have induced different molecular/biochemical adaptations/tolerances. Results highlight the importance of analysing effects of deep-sea mining in situ and in local species to adequately assess ecotoxicological effects under natural environmental conditions.This work was developed under the MIDAS project (Managing im-pacts of deep-sea resource exploitation), funded by the EuropeanCommission, European Union, 7th Framework Programme under thetheme“Sustainable management of Europe's deep sea and sub-seafloorresources”(Grant Agreement 603418). This work was also supported bythe Fundação para a Ciência e Tecnologia I.P. Portugal (FCT) and theDireção-Geral de Política do Mar (DGPM), Portugal through the projectMining2/2017/001–MiningImpact 2 (JPI Oceans), and FCT furtherfunded the grants CEECIND005262017 and UID/MAR/00350/2013.We acknowledge the captains and crews of the oceanographic ship“Pourquoi Pas?”, and the pilots of Victor 6000 Remotely OperatedVehicle, for their dedicated assistance during sampling of vent shrimps.We are also grateful to F. Lallier, chief scientist of the Biobaz cruise. Wewould like to warmly thank Océanopolis staffmembers, J-M Carré, SDelaporte and O Gouello, for their important contributions to shrimpmaintenance.info:eu-repo/semantics/publishedVersio

Re-education of Tumor-Associated Macrophages by CXCR2 Blockade Drives Senescence and Tumor Inhibition in Advanced Prostate Cancer

Tumor-associated macrophages (TAMs) represent a major component of the tumor microenvironment supporting tumorigenesis. TAMs re-education has been proposed as a strategy to promote tumor inhibition. However, whether this approach may work in prostate cancer is unknown. Here we find that Pten-null prostate tumors are strongly infiltrated by TAMs expressing C-X-C chemokine receptor type 2 (CXCR2), and activation of this receptor through CXCL2 polarizes macrophages toward an anti-inflammatory phenotype. Notably, pharmacological blockade of CXCR2 receptor by a selective antagonist promoted the re-education of TAMs toward a pro-inflammatory phenotype. Strikingly, CXCR2 knockout monocytes infused in Ptenpc−/−; Trp53pc−/− mice differentiated in tumor necrosis factor alpha (TNF-α)-releasing pro-inflammatory macrophages, leading to senescence and tumor inhibition. Mechanistically, PTEN-deficient tumor cells are vulnerable to TNF-α-induced senescence, because of an increase of TNFR1. Our results identify TAMs as targets in prostate cancer and describe a therapeutic strategy based on CXCR2 blockade to harness anti-tumorigenic potential of macrophages against this disease. © 2019 The Author(s) Di Mitri et al. show that CXCR2 blockade in prostate cancer triggers TAMs re-education, leading to tumor inhibition. CXCR2-KO monocytes infused in Ptenpc−/−; Trp53pc−/− tumor-bearing mice differentiate into TNFα-releasing pro-inflammatory macrophages that induce senescence in tumor cells. PTEN-null tumors display higher sensitivity to TNF-α-induced senescence because of TNFR1 upregulation

Social inequalities and correlates of psychotropic drug use among young adults: a population-based questionnaire study

<p>Abstract</p> <p>Background</p> <p>Use of psychotropic drugs is widespread in Europe, and is markedly more common in France than elsewhere. Young adults often fare less well than adolescents on health indicators (injury, homicide, and substance use). This population-based study assessed disparities in psychotropic drug use among people aged 18–29 from different socio-occupational groups and determined whether they were mediated by educational level, health status, income, health-related behaviours, family support, personality traits, or disability.</p> <p>Methods</p> <p>A total of 1,257 people aged 18–29, randomly selected in north-eastern France completed a post-mailed questionnaire covering sex, date of birth, height, weight, educational level, occupation, smoking habit, alcohol abuse, income, health-status, diseases, reported disabilities, self-reported personality traits, family support, and frequent psychotropic medication for tiredness, nervousness/anxiety or insomnia. The data were analyzed using the adjusted odds ratios (ORa) computed with logistic models.</p> <p>Results</p> <p>Use of psychotropic drugs was common (33.2%). Compared with upper/intermediate professionals, markedly high odds ratios adjusted for sex were found for manual workers (2.57, 95% CI 1.02–6.44), employees (2.58, 1.11–5.98), farmers/craftsmen/tradesmen (4.97, 1.13–21.8), students (2.40, 1.06–5.40), and housewives (3.82, 1.39–10.5). Adjusting for all the confounders considered reduced the estimates to a pronounced degree for manual workers (adjusted OR 1.49, non-significant) but only slightly for the other socio-occupational groups. The odds ratio for unemployed people did not reach statistical significance. The significant confounders were: sex, not-good health status, musculoskeletal disorders and other diseases, being worried, nervous or sad, and lack of family support (adjusted odds ratios between 1.60 and 2.50).</p> <p>Conclusion</p> <p>There were marked disparities among young adults from different socio-occupational groups. Sex, health status, musculoskeletal diseases, family support, and personality traits were related to use of psychotropic drugs. These factors mediated the higher risk strongly among manual workers and slightly among the other groups.</p

Implementation of a knowledge mobilization model to prevent peripheral venous catheter-related adverse events: PREBACP study-a multicenter cluster-randomized trial protocol.

BACKGROUND: Peripheral venous catheters are the most commonly used invasive devices in hospitals worldwide. Patients can experience multiple adverse events during the insertion, maintenance, and management of these devices. Health professionals aim to resolve the challenges of care variability in the use of peripheral venous catheter through adherence to clinical practice guidelines. The aim of this cluster-randomized controlled trial is to determine the efficacy of a multimodal intervention on incidence of adverse events associated with the use of peripheral venous catheters in adult hospital patients. Additional aims are to analyze the fidelity of nurses and the relationship between contextual factors on the use of best available and the outcomes of the intervention. METHODS: Five public hospitals in the Spanish National Health System, with diverse profiles, including one university hospital and four second-level hospitals, will be included. In total, 20 hospitalization wards will be randomized for this study by ward to one of two groups. Those in the first group receive an intervention that lasts 12 months implementing evidence-based practice in healthcare related to peripheral catheters through a multimodal strategy, which will contain updated and poster protocols insertion, maintenance and removal of peripheral venous catheters, technologies applied to e-learning, feedback on the results, user and family information related to peripheral catheter, and facilitation of the best evidence by face-to-face training session. PRIMARY OUTCOME MEASURES: Incidence of adverse events associated with the use of peripheral venous catheters is measured by assessing hospital records. SECONDARY OUTCOME MEASURES: Nurses' adherence to clinical practice guidelines, clinical outcomes, and the cost of implementing the multimodal intervention. DISCUSSION: Clinical implementation is a complex, multifaceted phenomenon which requires a deep understanding of decision-making, knowledge mobilization, and sense making in routine clinical practice. Likewise, the inclusion of strategies that promote fidelity to recommendations through multicomponent and multimodal intervention must be encouraged. The use of a transfer model could counterbalance one of the greatest challenges for organizations, the evaluation of the impact of the implementation of evidence in the professional context through quality indicators associated with prevention and control of infections. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10438530 . Registered 20 March 2018

Distinct Transcriptome Expression of the Temporal Cortex of the Primate Microcebus murinus during Brain Aging versus Alzheimer's Disease-Like Pathology

Aging is the primary risk factor of neurodegenerative disorders such as Alzheimer's disease (AD). However, the molecular events occurring during brain aging are extremely complex and still largely unknown. For a better understanding of these age-associated modifications, animal models as close as possible to humans are needed. We thus analyzed the transcriptome of the temporal cortex of the primate Microcebus murinus using human oligonucleotide microarrays (Affymetrix). Gene expression profiles were assessed in the temporal cortex of 6 young adults, 10 healthy old animals and 2 old, “AD-like” animals that presented ß-amyloid plaques and cortical atrophy, which are pathognomonic signs of AD in humans. Gene expression data of the 14,911 genes that were detected in at least 3 samples were analyzed. By SAM (significance analysis of microarrays), we identified 47 genes that discriminated young from healthy old and “AD-like” animals. These findings were confirmed by principal component analysis (PCA). ANOVA of the expression data from the three groups identified 695 genes (including the 47 genes previously identified by SAM and PCA) with significant changes of expression in old and “AD-like” in comparison to young animals. About one third of these genes showed similar changes of expression in healthy aging and in “AD-like” animals, whereas more than two thirds showed opposite changes in these two groups in comparison to young animals. Hierarchical clustering analysis of the 695 markers indicated that each group had distinct expression profiles which characterized each group, especially the “AD-like” group. Functional categorization showed that most of the genes that were up-regulated in healthy old animals and down-regulated in “AD-like” animals belonged to metabolic pathways, particularly protein synthesis. These data suggest the existence of compensatory mechanisms during physiological brain aging that disappear in “AD-like” animals. These results open the way to new exploration of physiological and “AD-like” aging in primates

Temperature Modulates Plant Defense Responses through NB-LRR Proteins

An elevated growth temperature often inhibits plant defense responses and renders plants more susceptible to pathogens. However, the molecular mechanisms underlying this modulation are unknown. To genetically dissect this regulation, we isolated mutants that retain disease resistance at a higher growth temperature in Arabidopsis. One such heat-stable mutant results from a point mutation in SNC1, a NB-LRR encoding gene similar to disease resistance (R) genes. Similar mutations introduced into a tobacco R gene, N, confer defense responses at elevated temperature. Thus R genes or R-like genes involved in recognition of pathogen effectors are likely the causal temperature-sensitive component in defense responses. This is further supported by snc1 intragenic suppressors that regained temperature sensitivity in defense responses. In addition, the SNC1 and N proteins had a reduction of nuclear accumulation at elevated temperature, which likely contributes to the inhibition of defense responses. These findings identify a plant temperature sensitive component in disease resistance and provide a potential means to generate plants adapting to a broader temperature range