Intrinsic up-regulation of 2-AG favors an area specific neuronal survival in different in vitro models of neuronal damage

BACKGROUND: The endocannabinoid 2-arachidonoyl glycerol (2-AG) acts as a retrograde messenger and modulates synaptic signaling e. g. in the hippocampus. 2-AG also exerts neuroprotective effects under pathological situations. To better understand the mechanism beyond physiological signaling we used Organotypic Entorhino-Hippocampal Slice Cultures (OHSC) and investigated the temporal regulation of 2-AG in different cell subsets during excitotoxic lesion and dendritic lesion of long range projections in the enthorhinal cortex (EC), dentate gyrus (DG) and the cornu ammonis region 1 (CA1). RESULTS: 2-AG levels were elevated 24 h after excitotoxic lesion in CA1 and DG (but not EC) and 24 h after perforant pathway transection (PPT) in the DG only. After PPT diacylglycerol lipase alpha (DAGL) protein, the synthesizing enzyme of 2-AG was decreased when Dagl mRNA expression and 2-AG levels were enhanced. In contrast to DAGL, the 2-AG hydrolyzing enzyme monoacylglycerol lipase (MAGL) showed no alterations in total protein and mRNA expression after PPT in OHSC. MAGL immunoreaction underwent a redistribution after PPT and excitotoxic lesion since MAGL IR disappeared in astrocytes of lesioned OHSC. DAGL and MAGL immunoreactions were not detectable in microglia at all investigated time points. Thus, induction of the neuroprotective endocannabinoid 2-AG might be generally accomplished by down-regulation of MAGL in astrocytes after neuronal lesions. CONCLUSION: Increase in 2-AG levels during secondary neuronal damage reflects a general neuroprotective mechanism since it occurred independently in both different lesion models. This intrinsic up-regulation of 2-AG is synergistically controlled by DAGL and MAGL in neurons and astrocytes and thus represents a protective system for neurons that is involved in dendritic reorganisation

Lost Opportunities to Reduce Periconception HIV Transmission: Safer Conception Counseling By South African Providers Addresses Perinatal but not Sexual HIV Transmission

Introduction: Safer conception strategies create opportunities for HIV-serodiscordant couples to realize fertility goals and minimize periconception HIV transmission. Patient–provider communication about fertility goals is the first step in safer conception counseling. Methods: We explored provider practices of assessing fertility intentions among HIV-infected men and women, attitudes toward people living with HIV (PLWH) having children, and knowledge and provision of safer conception advice. We conducted in-depth interviews (9 counselors, 15 nurses, 5 doctors) and focus group discussions (6 counselors, 7 professional nurses) in eThekwini District, South Africa. Data were translated, transcribed, and analyzed using content analysis with NVivo10 software. Results: Among 42 participants, median age was 41 (range, 28–60) years, 93% (39) were women, and median years worked in the clinic was 7 (range, 1–27). Some providers assessed women's, not men's, plans for having children at antiretroviral therapy initiation, to avoid fetal exposure to efavirenz. When conducted, reproductive counseling included CD4 cell count and HIV viral load assessment, advising mutual HIV status disclosure, and referral to another provider. Barriers to safer conception counseling included provider assumptions of HIV seroconcordance, low knowledge of safer conception strategies, personal feelings toward PLWH having children, and challenges to tailoring safer sex messages. Conclusions: Providers need information about HIV serodiscordance and safer conception strategies to move beyond discussing only perinatal transmission and maternal health for PLWH who choose to conceive. Safer conception counseling may be more feasible if the message is distilled to delaying conception attempts until the infected partner is on antiretroviral therapy. Designated and motivated nurse providers may be required to provide comprehensive safer conception counseling

Demonstrating the Use of Optical Fibres in Biomedical Sensing:A Collaborative Approach for Engagement and Education

This paper demonstrates how research at the intersection of physics, engineering, biology and medicine can be presented in an interactive and educational way to a non-scientific audience. Interdisciplinary research with a focus on prevalent diseases provides a relatable context that can be used to engage with the public. Respiratory diseases are significant contributors to avoidable morbidity and mortality and have a growing social and economic impact. With the aim of improving lung disease understanding, new techniques in fibre-based optical endomicroscopy have been recently developed. Here, we present a novel engagement activity that resembles a bench-to-bedside pathway. The activity comprises an inexpensive educational tool ($70) adapted from a clinical optical endomicroscopy system and tutorials that cover state-of-the-art research. The activity was co-created by high school science teachers and researchers in a collaborative way that can be implemented into any engagement development process

Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake

ObjectivesThis study aimed to explore the effects of an isocaloric Mediterranean diet (MD) intervention on metabolic health, gut microbiome and systemic metabolome in subjects with lifestyle risk factors for metabolic disease.DesignEighty-two healthy overweight and obese subjects with a habitually low intake of fruit and vegetables and a sedentary lifestyle participated in a parallel 8-week randomised controlled trial. Forty-three participants consumed an MD tailored to their habitual energy intakes (MedD), and 39 maintained their regular diets (ConD). Dietary adherence, metabolic parameters, gut microbiome and systemic metabolome were monitored over the study period.ResultsIncreased MD adherence in the MedD group successfully reprogrammed subjects' intake of fibre and animal proteins. Compliance was confirmed by lowered levels of carnitine in plasma and urine. Significant reductions in plasma cholesterol (primary outcome) and faecal bile acids occurred in the MedD compared with the ConD group. Shotgun metagenomics showed gut microbiome changes that reflected individual MD adherence and increase in gene richness in participants who reduced systemic inflammation over the intervention. The MD intervention led to increased levels of the fibre-degrading Faecalibacterium prausnitzii and of genes for microbial carbohydrate degradation linked to butyrate metabolism. The dietary changes in the MedD group led to increased urinary urolithins, faecal bile acid degradation and insulin sensitivity that co-varied with specific microbial taxa.ConclusionSwitching subjects to an MD while maintaining their energy intake reduced their blood cholesterol and caused multiple changes in their microbiome and metabolome that are relevant in future strategies for the improvement of metabolic health

Protist diversity on a nature reserve in NW England − with particular reference to their role in soil biogenic silicon pools

Soil protists play fundamental roles in many earth system processes, yet we are only beginning to understand the true diversity of the organisms involved. In this study we used conventional (microscopy-based) methods to characterise the diversity and estimate protist population sizes in soils from a variety of distinct habitats within Mere Sands Wood nature reserve in NW England. We produced population size data for over ninety soil protists belonging to two major eukaryotic functional groups: testate amoebae (TA) and diatoms, adding substantial ‘cryptic diversity’ to the nature reserves recorded biota. From these population size data we estimated relative contributions of TA and diatoms to soil biogenic silicon (BSi) pools and found significant correlations between taxon richness and the TA and diatom Si pool. This could indicate that protist functional diversity can influence terrestrial BSi pools, especially in early successional plant communities where TA and diatoms can potentially increase Si mineralisation and/or create Si ‘hot spots’ and hence, the biological availability of this element for subsequent plant uptake. TA were particularly abundant in mor humus type soils further supporting the idea that they could be important players in nutrient cycling in such soils. Overall, we demonstrate this is a useful approach in order to start to attempt to estimate the role of protists in the Si cycle and other ecological processes

Deaminase-independent inhibition of HIV-1 reverse transcription by APOBEC3G

APOBEC3G (A3G), a host protein that inhibits HIV-1 reverse transcription and replication in the absence of Vif, displays cytidine deaminase and single-stranded (ss) nucleic acid binding activities. HIV-1 nucleocapsid protein (NC) also binds nucleic acids and has a unique property, nucleic acid chaperone activity, which is crucial for efficient reverse transcription. Here we report the interplay between A3G, NC and reverse transcriptase (RT) and the effect of highly purified A3G on individual reactions that occur during reverse transcription. We find that A3G did not affect the kinetics of NC-mediated annealing reactions, nor did it inhibit RNase H cleavage. In sharp contrast, A3G significantly inhibited all RT-catalyzed DNA elongation reactions with or without NC. In the case of (−) strong-stop DNA synthesis, the inhibition was independent of A3G's catalytic activity. Fluorescence anisotropy and single molecule DNA stretching analyses indicated that NC has a higher nucleic acid binding affinity than A3G, but more importantly, displays faster association/disassociation kinetics. RT binds to ssDNA with a much lower affinity than either NC or A3G. These data support a novel mechanism for deaminase-independent inhibition of reverse transcription that is determined by critical differences in the nucleic acid binding properties of A3G, NC and RT

Methylome Analysis and Epigenetic Changes Associated with Menarcheal Age

CAD received funding from EU-Europe aid grant CRIS 2009/223–507.The EPIC cohort is supported by the Europe Against Cancer Program of the European Commission (SANCO). The individual centres also received funding from: Denmark (Danish Cancer Society); France (Ligue centre le Cancer, Institut Gustave Roussy, Mutuelle Ge´ne´rale de l’Education Nationale, and Institut National de la Sante´ et de la Recherche Me´dicale (INSERM)); Greece (Hellenic Ministry of Health, the Stavros Niarchos Foundation and the Hellenic Health Foundation); Germany (German Cancer Aid, German Cancer Research Center, and Federal Ministry of Education and Research (Grant 01-EA-9401)); Italy (Italian Association for Research on Cancer and the National Research Council); The Netherlands (Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, and Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF)); Spain (Health Research Fund (FIS) of the Spanish Ministry of Health (Exp 96/0032) and the participating regional governments and institutions); Sweden (Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Skane); and the United Kingdom (Cancer Research UK and Medical Research Council UK and Breast Cancer Campaign). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript