Syntectonic granite emplacement at different structural levels: The Closepet granite, South India

The Closepet granite, in South India, is a large (400 km long but only 30 km wide), elongate, Late Archaean granitic body. Structural levels from deep crust to upper levels crop out, as evidenced by a shallowing of paleo-depths from north to south all along the Closepet granite. This allows the study of the emplacement of the same granitic body at various crustal levels. Four zones have been identified: a root zone, where magmas are collected in active shear zones; a transfer zone, featuring large-scale magma ascent and crystal-liquid partitioning in the granitic 'mush'; a 'gap', where the mush was filtered, allowing only the liquids to rise; shallow intrusions, filled with this liquid. The Closepet granite was emplaced syntectonically. Field work and anisotropy of magnetic susceptibility allowed documentation of steep foliations with subhorizontal lineations, both in the root and transfer zones and in the shallow intrusions. Remote sensing evidenced a network of shear zones bounding the Closepet granite. In the porphyritic root and transfer zones, magmas cooled slowly, thus developing strong fabrics during large-scale dextral shearing. Ascent of residual liquids amidst the crystallizing solid framework was not recorded in the fabrics. However, these liquids were channelised through the gap and infilled the homogeneous shallow intrusions, where rapid cooling only permitted the development of feint, although wholly consistent, fabrics. © 2002 Elsevier Science Ltd. All rights reserved

Biochemical assessment of patients following ketogenic diets for epilepsy : current practice in the UK and Ireland

Biochemical assessment is recommended for patients prior to initiating and following a ketogenic diet (KD). There is no published literature regarding current practice in the UK and Ireland. We aimed to explore practice in comparison with international guidelines, determine approximate costs of biochemical testing in KD patients across the UK and Ireland, and promote greater consistency in KD services nationally. A survey was designed to determine the biochemical tests requested for patients at baseline, 3, 6, 12, 18, and 24 months + on KD. The survey was circulated to 39 centers across the UK and Ireland. Sixteen centers completed the survey. Full blood count, electrolytes, calcium, liver function tests (LFTs), lipid profile, and vitamin D were requested at all centers at baseline, in keeping with international guidelines. Bicarbonate, total protein, and urinalysis were less consistently requested. Magnesium and zinc were requested by all centers, despite not being specifically recommended for pre-diet evaluation in guidelines. Urea and electrolyte profiles and some LFTs were consistently requested at follow-up, in accordance with guidelines. Other LFTs and renal tests, full blood count, lipid profile, acylcarnitine profile, selenium, vitamin D, and urinalysis were less consistently requested at follow-up. The mean costs of the lowest and highest number of tests requested at baseline in our participating centers were £167.54 and £501.93; the mean costs of the lowest and highest number of tests requested at 3-month follow-up were £19.17 and £450.06. Biochemical monitoring of KD patients varies widely across the UK and Ireland and does not fully correspond to international best practice guidelines. With an ongoing drive for cost-effectiveness within health care, further work is needed to streamline practice while ensuring patient safety. [Abstract copyright: © 2019 The Authors. Epilepsia Open published by Wiley Periodicals Inc. on behalf of International League Against Epilepsy.

Grifonin-1: A Small HIV-1 Entry Inhibitor Derived from the Algal Lectin, Griffithsin

Background: Griffithsin, a 121-residue protein isolated from a red algal Griffithsia sp., binds high mannose N-linked glycans of virus surface glycoproteins with extremely high affinity, a property that allows it to prevent the entry of primary isolates and laboratory strains of T- and M-tropic HIV-1. We used the sequence of a portion of griffithsin's sequence as a design template to create smaller peptides with antiviral and carbohydrate-binding properties. Methodology/Results: The new peptides derived from a trio of homologous β-sheet repeats that comprise the motifs responsible for its biological activity. Our most active antiviral peptide, grifonin-1 (GRFN-1), had an EC50 of 190.8±11.0 nM in in vitro TZM-bl assays and an EC50 of 546.6±66.1 nM in p24gag antigen release assays. GRFN-1 showed considerable structural plasticity, assuming different conformations in solvents that differed in polarity and hydrophobicity. Higher concentrations of GRFN-1 formed oligomers, based on intermolecular β-sheet interactions. Like its parent protein, GRFN-1 bound viral glycoproteins gp41 and gp120 via the N-linked glycans on their surface. Conclusion: Its substantial antiviral activity and low toxicity in vitro suggest that GRFN-1 and/or its derivatives may have therapeutic potential as topical and/or systemic agents directed against HIV-1

Cell surface IL-1α trafficking is specifically inhibited by interferon-γ, and associates with the membrane via IL-1R2 and GPI anchors.

IL-1 is a powerful cytokine that drives inflammation and modulates adaptive immunity. Both IL-1α and IL-1β are translated as proforms that require cleavage for full cytokine activity and release, while IL-1α is reported to occur as an alternative plasma membrane-associated form on many cell types. However, the existence of cell surface IL-1α (csIL-1α) is contested, how IL-1α tethers to the membrane is unknown, and signaling pathways controlling trafficking are not specified. Using a robust and fully validated system, we show that macrophages present bona fide csIL-1α after ligation of TLRs. Pro-IL-1α tethers to the plasma membrane in part through IL-1R2 or via association with a glycosylphosphatidylinositol-anchored protein, and can be cleaved, activated, and released by proteases. csIL-1α requires de novo protein synthesis and its trafficking to the plasma membrane is exquisitely sensitive to inhibition by IFN-γ, independent of expression level. We also reveal how prior csIL-1α detection could occur through inadvertent cell permeabilisation, and that senescent cells do not drive the senescent-associated secretory phenotype via csIL-1α, but rather via soluble IL-1α. We believe these data are important for determining the local or systemic context in which IL-1α can contribute to disease and/or physiological processes.Work was funded by British Heart Foundation Grants FS/13/3/30038, FS/18/19/33371 and RG/16/8/32388 to MCHC, the BHF Cambridge CRE RE/13/6/30180, and the Cambridge NIHR Biomedical Research Centr

Theoretical Uncertainties in Electroweak Boson Production Cross Sections at 7, 10, and 14 TeV at the LHC

We present an updated study of the systematic errors in the measurements of the electroweak boson cross-sections at the LHC for various experimental cuts for a center of mass energy of 7, 10 and 14 TeV. The size of both electroweak and NNLO QCD contributions are estimated, together with the systematic error from the parton distributions. The effects of new versions of the MSTW, CTEQ, and NNPDF PDFs are considered.Comment: PDFLatex with JHEP3.cls. 22 pages, 43 figures. Version 2 adds the CT10W PDF set to analysis and updates the final systematic error table and conclusions, plus several citations and minor wording changes. Version 3 adds some references on electroweak and mixed QED/QCD corrections. Version 4 adds more references and acknowledgement

The genetics and expression of canine antigen receptors analysed with a novel RNA-seq strategy.

INTRODUCTION Dogs are an excellent model for human disease, e.g. the treatment of canine lymphoma is often predictive of the human response to that treatment. However, an incomplete picture of their antigen-receptor (AR) gene loci and a limited set of available experimental tools has restricted their use. This work advances the annotation of the canine AR loci, develops methods to interrogate their expression patterns, and looks into breed-specific features of the loci. METHODS A bioinformatic approach alongside unbiased RNA-seq was used to complete the annotation of the canine AR genes, and these sequences were used to query 107 whole genome sequences from 19 breeds. A 5’RACE strategy was developed to selectively amplify ARs for next generation sequencing, and this was applied to RNA isolated from canine peripheral blood samples. RESULTS >5,500 novel alleles were identified across the ~550 gene segments (of which 326 were newly annotated) of the AR loci, yielding insight into AR evolution as well as confirming the greater conservation between dog and human than mouse with either. The 5’RACE strategy was validated with a pilot study that cast light onto the baseline expression and mutation patterns of healthy dogs, finding they closely mirrored their human counterparts. CONCLUSION This work brings our understanding of the genetics and expression of ARs in dogs to the same high standard as mice and men. The large number of genome sequences serves as a reference for future studies, and has allowed statistically powerful conclusions to be drawn on the pressures that have shaped these loci. Finally, it confirms the dog as a superior immunological model, particularly in the context of the high conservation seen in both sequence and expression features

Recommendations for exercise adherence measures in musculoskeletal settings : a systematic review and consensus meeting (protocol)

Background: Exercise programmes are frequently advocated for the management of musculoskeletal disorders; however, adherence is an important pre-requisite for their success. The assessment of exercise adherence requires the use of relevant and appropriate measures, but guidance for appropriate assessment does not exist. This research will identify and evaluate the quality and acceptability of all measures used to assess exercise adherence within a musculoskeletal setting, seeking to reach consensus for the most relevant and appropriate measures for application in research and/or clinical practice settings. Methods/design: There are two key stages to the proposed research. First, a systematic review of the quality and acceptability of measures used to assess exercise adherence in musculoskeletal disorders; second, a consensus meeting. The systematic review will be conducted in two phases and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure a robust methodology. Phase one will identify all measures that have been used to assess exercise adherence in a musculoskeletal setting. Phase two will seek to identify published and unpublished evidence of the measurement and practical properties of identified measures. Study quality will be assessed against the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) guidelines. A shortlist of best quality measures will be produced for consideration during stage two: a meeting of relevant stakeholders in the United Kingdom during which consensus on the most relevant and appropriate measures of exercise adherence for application in research and/or clinical practice settings will be sought. Discussion: This study will benefit clinicians who seek to evaluate patients’ levels of exercise adherence and those intending to undertake research, service evaluation, or audit relating to exercise adherence in the musculoskeletal field. The findings will impact upon new research studies which aim to understand the factors that predict adherence with exercise and which test different adherence-enhancing interventions. PROSPERO reference: CRD4201300621

Monitoring health inequalities: life expectancy and small area deprivation in New Zealand

BACKGROUND: Socioeconomic and ethnic inequalities in health are of great concern, and life expectancy provides a readily understood means of monitoring such inequalities. The objectives of this study are to (1) measure life expectancy by socioeconomic deprivation and ethnicity, and (2) describe trends in the deprivation gradient in life expectancy since the mid-1990s. METHODS: Three years of national mortality data have been combined with mid-point population denominators to produce life tables within nationally determined levels of small area deprivation (NZDep96) for three ethnic group: European, Mäori and Pacific peoples. This process has been repeated for the periods 1995–97, 1996–98, 1997–99 and 1998–2000. RESULTS: There was a strong relationship between increasing small area deprivation and decreasing life expectancy. Through the mid- to late 1990s, males living in the most deprived small areas in New Zealand experienced life expectancies at birth approximately nine years less than their counterparts living in the least deprived areas; for females the corresponding difference was under seven years. Mäori and Pacific life expectancies at birth were lower than those of Europeans at each level of deprivation. Over the study period (1995–2000) the gradient in life expectancy across deprivation deciles remained stable. CONCLUSION: Small area deprivation analyses of life expectancy could be repeated routinely at regular intervals, which would provide a useful approach to monitoring trends in socioeconomic, geographic, ethnic and gender inequalities in mortality

Sporormiella as a tool for detecting the presence of large herbivores in the Neotropics

The reliability of using the abundance of Sporormiella spores as a proxy for the presence and abundance of megaherbivores was tested in southern Brazil. Mud-water interface samples from nine lakes, in which cattle-use was categorized as high, medium, or low, were assayed for Sporormiella representation. The sampling design allowed an analysis of both the influence of the number of animals using the shoreline and the distance of the sampling site from the nearest shoreline. Sporormiella was found to be a reliable proxy for the presence of large livestock. The concentration and abundance of spores declined from the edge of the lake toward the center, with the strongest response being in sites with high livestock use. Consistent with prior studies in temperate regions, we find that Sporormiella spores are a useful proxy to study the extinction of Pleistocene megafauna or the arrival of European livestock in Neotropical landscapes