Zircon ages in granulite facies rocks: decoupling from geochemistry above 850 °C?

Granulite facies rocks frequently show a large spread in their zircon ages, the interpretation of which raises questions: Has the isotopic system been disturbed? By what process(es) and conditions did the alteration occur? Can the dates be regarded as real ages, reflecting several growth episodes? Furthermore, under some circumstances of (ultra-)high-temperature metamorphism, decoupling of zircon U–Pb dates from their trace element geochemistry has been reported. Understanding these processes is crucial to help interpret such dates in the context of the P–T history. Our study presents evidence for decoupling in zircon from the highest grade metapelites (> 850 °C) taken along a continuous high-temperature metamorphic field gradient in the Ivrea Zone (NW Italy). These rocks represent a well-characterised segment of Permian lower continental crust with a protracted high-temperature history. Cathodoluminescence images reveal that zircons in the mid-amphibolite facies preserve mainly detrital cores with narrow overgrowths. In the upper amphibolite and granulite facies, preserved detrital cores decrease and metamorphic zircon increases in quantity. Across all samples we document a sequence of four rim generations based on textures. U–Pb dates, Th/U ratios and Ti-in-zircon concentrations show an essentially continuous evolution with increasing metamorphic grade, except in the samples from the granulite facies, which display significant scatter in age and chemistry. We associate the observed decoupling of zircon systematics in high-grade non-metamict zircon with disturbance processes related to differences in behaviour of non-formula elements (i.e. Pb, Th, U, Ti) at high-temperature conditions, notably differences in compatibility within the crystal structure

Thresholds of riparian forest use by terrestrial mammals in a fragmented Amazonian deforestation frontier

Species persistence in fragmented landscapes is intimately related to the quality, structure, and context of remaining habitat remnants. Riparian vegetation is legally protected within private landholdings in Brazil, so we quantitatively assessed occupancy patterns of terrestrial mammals in these remnants, examining under which circumstances different species effectively use them. We selected 38 riparian forest patches and five comparable riparian sites within continuous forest, at which we installed four to five camera-traps per site (199 camera-trap stations). Terrestrial mammal assemblages were sampled for 60 days per station during the dry seasons of 2013 and 2014. We modelled species occupancy and detection probabilities within riparian forest remnants, and examined the effects of patch size, habitat quality, and landscape structure on occupancy probabilities. We then scaled-up modelled occupancies to all 1915 riparian patches throughout the study region to identify which remnants retain the greatest potential to work as habitat for terrestrial vertebrates. Of the ten species for which occupancy was modelled, six responded to forest quality (remnant degradation, cattle intrusion, palm aggregations, and understorey density) or structure (remnant width, isolation, length, and area of the patch from which it originates). Patch suitability was lower considering habitat quality than landscape structure, and virtually all riparian remnants were unsuitable to maintain a high occupancy probability for all species that responded to forest patch quality or structure. Beyond safeguarding legal compliance concerning riparian remnant amount, ensuring terrestrial vertebrate persistence in fragmented landscapes will require curbing the drivers of forest degradation within private landholdings

Perceptions and Attitudes of Egyptian Health Professionals and Policy-Makers towards Pharmaceutical Sales Representatives and Other Promotional Activities

Pharmaceutical promotion activities in low and middle-income countries are often neither regulated nor monitored. While Egypt has the highest population and per capita use of medicines in the Arab world, we know very little about pharmaceutical companies promotional activities in the country.To explore and analyze the perceptions of physicians towards promotional and marketing activities of pharmaceutical companies among physicians and pharmacists in Egypt.Perspectives of different healthcare system stakeholders were explored through semi-structured, in-depth interviews conducted in 2014 in Cairo, Egypt. Interviewees were chosen via purposive sampling and snowball technique. Each interview was recorded and transcribed. Then qualitative, thematic analysis was conducted with the help of NVIVO software.The majority of physicians and pharmacists acknowledged exposure to pharmaceutical promotion. It was commonly believed that interaction with the pharmaceutical industry is necessary and both associated risks and benefits were acknowledged. The interviewed physicians considered themselves competent enough to minimize risks and maximize benefits to their prescribing habits. Views diverged on the extent and magnitude of the risks and benefits of pharmaceutical promotion, especially in regard to the influence on patients' health.Pharmaceutical promotion in Egypt is intensely directed at prescribers and dispensers. Physicians, pharmacists and policymakers expressed little skepticism to the influence of promotion towards their individual prescribing. Raising awareness of the pitfalls of pharmaceutical promotion is necessary, especially among the less experienced physicians

Validation of N-myristoyltransferase as an antimalarial drug target using an integrated chemical biology approach

Malaria is an infectious disease caused by parasites of the genus Plasmodium, which leads to approximately one million deaths per annum worldwide. Chemical validation of new antimalarial targets is urgently required in view of rising resistance to current drugs. One such putative target is the enzyme N-myristoyltransferase, which catalyses the attachment of the fatty acid myristate to protein substrates (N-myristoylation). Here, we report an integrated chemical biology approach to explore protein myristoylation in the major human parasite P. falciparum, combining chemical proteomic tools for identification of the myristoylated and glycosylphosphatidylinositol-anchored proteome with selective small-molecule N-myristoyltransferase inhibitors. We demonstrate that N-myristoyltransferase is an essential and chemically tractable target in malaria parasites both in vitro and in vivo, and show that selective inhibition of N-myristoylation leads to catastrophic and irreversible failure to assemble the inner membrane complex, a critical subcellular organelle in the parasite life cycle. Our studies provide the basis for the development of new antimalarials targeting N-myristoyltransferase

Genome-wide transcriptional profiling of appressorium development by the rice blast fungus Magnaporthe oryzae.

addresses: College of Life and Environmental Sciences, University of Exeter, Exeter, United Kingdom.notes: PMCID: PMC3276559The rice blast fungus Magnaporthe oryzae is one of the most significant pathogens affecting global food security. To cause rice blast disease the fungus elaborates a specialised infection structure called an appressorium. Here, we report genome wide transcriptional profile analysis of appressorium development using next generation sequencing (NGS). We performed both RNA-Seq and High-Throughput SuperSAGE analysis to compare the utility of these procedures for identifying differential gene expression in M. oryzae. We then analysed global patterns of gene expression during appressorium development. We show evidence for large-scale gene expression changes, highlighting the role of autophagy, lipid metabolism and melanin biosynthesis in appressorium differentiation. We reveal the role of the Pmk1 MAP kinase as a key global regulator of appressorium-associated gene expression. We also provide evidence for differential expression of transporter-encoding gene families and specific high level expression of genes involved in quinate uptake and utilization, consistent with pathogen-mediated perturbation of host metabolism during plant infection. When considered together, these data provide a comprehensive high-resolution analysis of gene expression changes associated with cellular differentiation that will provide a key resource for understanding the biology of rice blast disease

Evolutionary genomics of a cold-adapted diatom: Fragilariopsis cylindrus

The Southern Ocean houses a diverse and productive community of organisms1, 2. Unicellular eukaryotic diatoms are the main primary producers in this environment, where photosynthesis is limited by low concentrations of dissolved iron and large seasonal fluctuations in light, temperature and the extent of sea ice3, 4, 5, 6, 7. How diatoms have adapted to this extreme environment is largely unknown. Here we present insights into the genome evolution of a cold-adapted diatom from the Southern Ocean, Fragilariopsis cylindrus8, 9, based on a comparison with temperate diatoms. We find that approximately 24.7 per cent of the diploid F. cylindrus genome consists of genetic loci with alleles that are highly divergent (15.1 megabases of the total genome size of 61.1 megabases). These divergent alleles were differentially expressed across environmental conditions, including darkness, low iron, freezing, elevated temperature and increased CO2. Alleles with the largest ratio of non-synonymous to synonymous nucleotide substitutions also show the most pronounced condition-dependent expression, suggesting a correlation between diversifying selection and allelic differentiation. Divergent alleles may be involved in adaptation to environmental fluctuations in the Southern Ocean

Strength Training for Arthritis Trial (START): design and rationale

Background Muscle loss and fat gain contribute to the disability, pain, and morbidity associated with knee osteoarthritis (OA), and thigh muscle weakness is an independent and modifiable risk factor for it. However, while all published treatment guidelines recommend muscle strengthening exercise to combat loss of muscle mass and strength in knee OA patients, previous strength training studies either used intensities or loads below recommended levels for healthy adults or were generally short, lasting only 6 to 24 weeks. The efficacy of high-intensity strength training in improving OA symptoms, slowing progression, and affecting the underlying mechanisms has not been examined due to the unsubstantiated belief that it might exacerbate symptoms. We hypothesize that in addition to short-term clinical benefits, combining greater duration with high-intensity strength training will alter thigh composition sufficiently to attain long-term reductions in knee-joint forces, lower pain levels, decrease inflammatory cytokines, and slow OA progression. Methods/Design This is an assessor-blind, randomized controlled trial. The study population consists of 372 older (age ≥ 55 yrs) ambulatory, community-dwelling persons with: (1) mild-to-moderate medial tibiofemoral OA (Kellgren-Lawrence (KL) = 2 or 3); (2) knee neutral or varus aligned knee ( -2° valgus ≤ angle ≤ 10° varus); (3) 20 kg.m-2 ≥ BMI ≤ 45 kg.m-2; and (3) no participation in a formal strength-training program for more than 30 minutes per week within the past 6 months. Participants are randomized to one of 3 groups: high-intensity strength training (75-90% 1Repetition Maximum (1RM)); low-intensity strength training (30-40%1RM); or healthy living education. The primary clinical aim is to compare the interventions’ effects on knee pain, and the primary mechanistic aim is to compare their effects on knee-joint compressive forces during walking, a mechanism that affects the OA disease pathway. Secondary aims will compare the interventions’ effects on additional clinical measures of disease severity (e.g., function, mobility); disease progression measured by x-ray; thigh muscle and fat volume, measured by computed tomography (CT); components of thigh muscle function, including hip abductor strength and quadriceps strength, and power; additional measures of knee-joint loading; inflammatory and OA biomarkers; and health-related quality of life. Discussion Test-retest reliability for the thigh CT scan was: total thigh volume, intra-class correlation coefficients (ICC) = 0.99; total fat volume, ICC = 0.99, and total muscle volume, ICC = 0.99. ICC for both isokinetic concentric knee flexion and extension strength was 0.93, and for hip-abductor concentric strength was 0.99. The reliability of our 1RM testing was: leg press, ICC = 0.95; leg curl, ICC = 0.99; and leg extension, ICC = 0.98. Results of this trial will provide critically needed guidance for clinicians in a variety of health professions who prescribe and oversee treatment and prevention of OA-related complications. Given the prevalence and impact of OA and the widespread availability of this intervention, assessing the efficacy of optimal strength training has the potential for immediate and vital clinical impact

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Abnormal macrophage response to microbial stimulus in a 43-year-old man with a severe form of atherosclerosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>New evidence indicates infections are emerging as risk factors for atherosclerosis although their specific role in the development and progression of atherosclerosis is still unclear.</p> <p>Case presentation</p> <p>A 43-year-old Caucasian man who had been treated for four years for multiple sclerosis progressively manifested systemic hypertension, polycythemia, peripheral arterial occlusion with intermittent claudication, and persistent headaches. In 2006, an instrumental analysis (magnetic resonance imaging) of our patient revealed widespread fibrocalcific atherosclerotic lesions which accounted for all his current symptoms, including those related to microbial stimulus. Two particular aspects were of interest, namely a lack of conventional cardiovascular risk factors and a negative family history for cardiovascular events. His chemical blood tests all yielded negative findings although a low positive hepatitis C virus-ribonucleic acid titer was detected. The titer had progressively increased and worsening atherosclerosis threatened the life of our patient. Interferon therapy was not appropriate for our patient due to the severe adverse effects observed shortly after its administration.</p> <p>Conclusions</p> <p>The reaction of individual cells to infections may provide an explanation as to why individuals with a similar microbial burden, corrected for the presence of other risk factors, display a different susceptibility to developing or worsening atherosclerosis. The identification of susceptible individuals and the treatment even of silent infections may provide an additional tool against atherosclerosis and its clinical complications. The evaluation of cell susceptibility before and after the correction of risk factors may contribute to the assessment of the efficacy of drug therapy.</p

QCD with dynamical Wilson fermions

Results for the spectrum and the F and D parameters are obtained with precision similar to that in the quenched approximation. Present data for m{sub q} {ge} m{sub s} show measurable effects due to vacuum polarization only in the pion-Nucleon {Sigma} term suggesting that {Sigma}{sup sea} {approximately} {Sigma}{sup val}. The lattice update is being done on the Connection Machine which is very well suited to simulate QCD with 2 flavors of Wilson fermions (with mass close to the strange quark) using HMCA on 16{sup 3} {times} 32 lattices. 7 refs., 3 figs., 5 tabs