Association between osteoarthritis and cardiovascular disease: systematic review and meta-analysis

Background: To examine for a possible relationship between osteoarthritis and cardiovascular disease (CVD). Design: A systematic review and meta-analysis Methods: Published and unpublished literature from: MEDLINE, EMBASE, CINAHL, the Cochrane Library, OpenGrey and clinical trial registers. Search to 22nd November 2014. Cohort, case-control, randomised and non-randomised controlled trial papers reporting the prevalence of CVD in osteoarthritis were included. Results: Fifteen studies with 32,278,744 individuals were eligible. Pooled prevalence for overall CVD pathology in people with osteoarthritis was 38.4% (95% Confidence interval (CI): 37.2% to 39.6%). Individuals with osteoarthritis were almost three times as likely to have heart failure (Relative Risk (RR): 2.80; 95% CI: 2.25 to 3.49) or ischaemic heart disease (RR: 1.78; 95% CI: 1.18 to 2.69) compared to matched non-osteoarthritis cohorts. No significant difference was detected between the two groups for the risk of experiencing myocardial infarction or stroke. There was a three-fold decrease in the risk of experiencing a transient ischaemic attack in the osteoarthritis cohort compared to the non-osteoarthritis group. Conclusions: Prevalence of CVD in patients with OA is significant. There was an observed increased risk of incident heart failure and ischaemic heart disease in people with OA compared to matched controls. However the relationship between OA and CVD is not straight-forward and there is a need to better understand the potential common pathways linking pathophysiological mechanisms

Deep dielectric charging of regolith within the Moon\u27s permanently shadowed regions

Abstract Energetic charged particles, such as galactic cosmic rays (GCRs) and solar energetic particles (SEPs), can penetrate deep within the lunar surface, resulting in deep dielectric charging. This charging process depends on the GCR and SEP currents, as well as on the regolith\u27s electrical conductivity and permittivity. In permanently shadowed regions (PSRs) near the lunar poles, the discharging timescales are on the order of a lunation (∼20 days). We present the first predictions for deep dielectric charging of lunar regolith. To estimate the resulting subsurface electric fields, we develop a data-driven, one-dimensional, time-dependent model. For model inputs, we use GCR data from the Cosmic Ray Telescope for the Effects of Radiation on board the Lunar Reconnaissance Orbiter and SEP data from the Electron, Proton, and Alpha Monitor on the Advanced Composition Explorer. We find that during the recent solar minimum, GCRs create persistent electric fields up to ∼700 V/m. We also find that large SEP events create transient but strong electric fields (≥106 V/m) that may induce dielectric breakdown. Such breakdown would likely result in significant modifications to the physical and chemical properties of the lunar regolith within PSRs. Key Points Energetic charged particles deep dielectrically charge the lunar regolithWe model the resulting subsurface electric fieldsThe electric fields may be great enough to induce dielectric breakdown

Dielectric breakdown weathering of the Moon\u27s polar regolith

Abstract Galactic cosmic rays and solar energetic particles (SEPs) can charge the Moon\u27s subsurface, a process expected to be particularly important in the polar regions. Experiments have shown that sufficient fluences (i.e., time-integrated fluxes) of energetic charged particles can cause dielectric breakdown, in which the electric field rapidly vaporizes small, filamentary channels within a dielectric. Lunar regolith has both the characteristics and, in some polar locations, the environment needed to make breakdown likely. We combine the Jet Propulsion Laboratory proton fluence model with temperature measurements from the Lunar Reconnaissance Orbiter\u27s (LRO\u27s) Diviner instrument and related temperature modeling to estimate how often breakdown occurs in the polar regions. We find that all gardened regolith within permanently shadowed regions (PSRs) has likely experienced up to 2×106 SEP events capable of causing breakdown, while the warmest polar regions have experienced about 2 orders of magnitude fewer events. We also use measurements from the Cosmic Ray Telescope for the Effects of Radiation on LRO to show that at least two breakdown-inducing events may have occurred since LRO arrived at the Moon in 2009. Finally, we discuss how such “breakdown weathering” may increase the percentage of fine and monomineralic grains within PSRs; explain the presence of so-called “fairy castle” regolith structures; and contribute to other low-albedo features detected by LRO\u27s Lyman Alpha Mapping Project, possibly establishing a correlation between these features and the average temperatures within craters that are only partly in permanent shadow

The complete mitochondrial genome of Epomophorus gambianus (Chiroptera: Pteropodidae) and its phylogenetic analysis.

The Gambian epauletted fruit bat, Epomophorus gambianus, is widely distributed across sub-Saharan Africa. Its assembled and annotated mitochondrial genome (GenBank accession no. KT963027) is 16,702 bases in length, containing 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes and two non-coding regions: the control region (D-loop) and the origin of light-strand replication (OL). The average base composition is 32.2% A; 27.6% C; 14% G; and 26.1% T. The mitogenome presented a structural composition greatly conserved between members of the Pteropodidae family.This is the final version of the article. It first appeared from Taylor & Francis via https://doi.org/10.1080/23802359.2016.118199

Evaluation of the antigen-experienced B-cell receptor repertoire in healthy children and adults

Upon antigen recognition via their B cell receptor (BR), B cells migrate to the germinal center where they undergo somatic hypermutation (SHM) to increase their affinity for the antigen, and class switch recombination (CSR) to change the effector function of the secreted antibodies. These steps are essential to create an antigen-experienced BR repertoire that efficiently protects the body against pathogens. At the same time, the BR repertoire should be selected to protect against responses to self-antigen or harmless antigens. Insights into the processes of SHM, selection, and CSR can be obtained by studying the antigen-experienced BR repertoire. Currently, a large reference data set of healthy children and adults, which ranges from neonates to the elderly, is not available. In this study, we analyzed the antigen-experienced repertoire of 38 healthy donors (HD), ranging from cord blood to 74 years old, by sequencing IGA and IGG transcripts using next generation sequencing. This resulted in a large, freely available reference data set containing 412,890 IGA and IGG transcripts. We used this data set to study mutation levels, SHM patterns, antigenic selection, and CSR from birth to elderly HD. Only small differences were observed in SHM patterns, while the mutation levels increase in early childhood and stabilize at 6 years of age at around 7%. Furthermore, comparison of the antigen-experienced repertoire with sequences from the naive immune repertoire showed that features associated with autoimmunity such as long CDR3 length and IGHV4-34 usage are reduced in the antigen-experienced repertoire. Moreover, IGA2 and IGG2 usage was increased in HD in higher age categories, while IGG1 usage was decreased. In addition, we studied clonal relationship in the different samples. Clonally related sequences were found with different subclasses. Interestingly, we found transcripts with the same CDR1-CDR3 sequence, but different subclasses. Together, these data suggest that a single antigen can provoke a B-cell response with BR of different subclasses and that, during the course of an immune response, some B cells change their isotype without acquiring additional SHM or can directly switch to different isotypes

Phosphorylation-dependent BRD4 dimerization and implications for therapeutic inhibition of BET family proteins.

Funder: AstraZenecaFunder: AstraZeneca postdoc fundBromodomain-containing protein 4 (BRD4) is an epigenetic reader and oncology drug target that regulates gene transcription through binding to acetylated chromatin via bromodomains. Phosphorylation by casein kinase II (CK2) regulates BRD4 function, is necessary for active transcription and is involved in resistance to BRD4 drug inhibition in triple-negative breast cancer. Here, we provide the first biophysical analysis of BRD4 phospho-regulation. Using integrative structural biology, we show that phosphorylation by CK2 modulates the dimerization of human BRD4. We identify two conserved regions, a coiled-coil motif and the Basic-residue enriched Interaction Domain (BID), essential for the BRD4 structural rearrangement, which we term the phosphorylation-dependent dimerization domain (PDD). Finally, we demonstrate that bivalent inhibitors induce a conformational change within BRD4 dimers in vitro and in cancer cells. Our results enable the proposal of a model for BRD4 activation critical for the characterization of its protein-protein interaction network and for the development of more specific therapeutics

A Strategy for Finding Near Earth Objects with the SDSS Telescope

We present a detailed observational strategy for finding Near Earth Objects (NEOs) with the Sloan Digital Sky Survey (SDSS) telescope. We investigate strategies in normal, unbinned mode as well as binning the CCDs 2x2 or 3x3, which affects the sky coverage rate and the limiting apparent magnitude. We present results from 1 month, 3 year and 10 year simulations of such surveys. For each cadence and binning mode, we evaluate the possibility of achieving the Spaceguard goal of detecting 90% of 1 km NEOs (absolute magnitude H <= 18 for an albedo of 0.1). We find that an unbinned survey is most effective at detecting H <= 20 NEOs in our sample. However, a 3x3 binned survey reaches the Spaceguard Goal after only seven years of operation. As the proposed large survey telescopes (PanStarss; LSST) are at least 5-10 years from operation, an SDSS NEO survey could make a significant contribution to the detection and photometric characterization of the NEO population.Comment: Accepted by AJ -- 12 pages, 11 figure

Structural dissection of a complex Bacteroides ovatus gene locus conferring xyloglucan metabolism in the human gut

The human gastrointestinal tract harbours myriad bacterial species, collectively termed the microbiota, that strongly influence human health. Symbiotic members of our microbiota play a pivotal role in the digestion of complex carbohydrates that are otherwise recalcitrant to assimilation. Indeed, the intrinsic human polysaccharide-degrading enzyme repertoire is limited to various starch-based substrates; more complex polysaccharides demand microbial degradation. Select Bacteroidetes are responsible for the degradation of the ubiquitous vegetable xyloglucans (XyGs), through the concerted action of cohorts of enzymes and glycan-binding proteins encoded by specific xyloglucan utilization loci (XyGULs). Extending recent (meta) genomic, transcriptomic and biochemical analyses, significant questions remain regarding the structural biology of the molecular machinery required for XyG saccharification. Here, we reveal the three-dimensional structures of an α-xylosidase, a β-glucosidase, and two α-L-arabinofuranosidases from the Bacteroides ovatus XyGUL. Aided by bespoke ligand synthesis, our analyses highlight key adaptations in these enzymes that confer individual specificity for xyloglucan side chains and dictate concerted, stepwise disassembly of xyloglucan oligosaccharides. In harness with our recent structural characterization of the vanguard endo-xyloglucanse and cell-surface glycan-binding proteins, the present analysis provides a near-complete structural view of xyloglucan recognition and catalysis by XyGUL proteins

Treatment variation in stent choice in patients with stable or unstable coronary artery disease

Aim: Variations in treatment are the result of differences in demographic and clinical factors (e.g. anatomy), but physician and hospital factors may also contribute to treatment variation. The choice of treatment is considered important since it could lead to differences in long-term outcomes. This study explores the associations with stent choice: i.e. drug-eluting stent (DES) versus bare-metal stents (BMS) for Dutch patients diagnosed with stable or unstable coronary artery disease (CAD). Methods & results: Associations with treatment decisions were based on a prospective cohort of 692 patients with stable or unstable CAD. Of those patients, 442 patients were treated with BMS or DES. Multiple logistic regression analyses were performed to identify variables associated with stent choice. Bivariate analyses showed that NYHA class, number of diseased vessels, previous percutaneous coronary intervention, smoking, diabetes, and the treating hospital were associated with stent type. After correcting for other associations the treating hospital remained significantly associated with stent type in the stable CAD population. Conclusions: This study showed that several factors were associated with stent choice. While patients generally appear to receive the most optimal stent given their clinical characteristics, stent choice seems partially determined by the treating hospital, which may lead to differences in longterm outcome

Evaluating Iodine Uptake in a Crystalline Sponge Using Dynamic X-ray Crystallography

The uptake of gaseous iodine into the crystalline sponge material [(ZnI2)3(tpt)2]·0.7triphenylene·0.3PhNO2·0.7C6H12 1 (tpt = 2,4,6-tris(4-pyridyl)-1,3,5-triazine) has been monitored by dynamic X-ray diffraction and thermogravimetric analysis. The X-ray analyses have enabled the location, quantity, uptake rate, and subsequent chemistry of the iodine upon inclusion into the pores to be determined. An uptake of 6.0 wt % (0.43 I2 per formula unit) was observed crystallographically over a period of 90 min before crystal degradation occurred. The included iodine molecules interact with the iodine atoms of the ZnI2 nodes at three different sites, forming coordinated I3– ions. The results contrast to recent observations on [(ZnI2)3(tpt)2] without the triphenylene guests which show the presence of I42– ions with low quantities of absorbed iodine