Expression of the autoimmune Fcgr2b NZW allele fails to be upregulated in germinal center B cells and is associated with increased IgG production

The inhibitory receptor FcγRIIb regulates B-cell functions. Genetic studies have associated Fcgr2b polymorphisms and lupus susceptibility in both humans and murine models, in which B cells express reduced FcγRIIb levels. Furthermore, FcγRIIb absence results in lupus on the appropriate genetic background, and lentiviral-mediated FcγRIIb overexpression prevents disease in the NZM2410 lupus mouse. The NZM2410/NZW allele Fcgr2b is, however, located in-between Sle1a and Sle1b, two potent susceptibility loci, making it difficult to evaluate Fcr2bNZW independent contribution. By using two congenic strains that each carries only Sle1a (B6.Sle1a(15–353)), or Fcr2bNZW in the absence of Sle1a or Sle1b (B6.Sle1(111–148)), we show that the Fcr2bNZW allele does not upregulate its expression on germinal center B cells and plasma cells, as does the C57BL/6 allele on B6.Sle1a(15–353) B cells. Furthermore, in the absence of the flanking Sle1a and Sle1b, Fcr2bNZW does not produce an autoimmune phenotype, but is associated with an increased number of class-switched plasma cells. These results show that while a lower level of FcγRIIb does not by itself induce the development of autoreactive B cells, it has the potential to amplify the contribution of autoreactive B cells induced by other lupus-susceptibility loci by enhancing the production of class-switched plasma cells

Synthesis and antibacterial effects of cobalt–cellulose magnetic nanocomposites

© The Royal Society of Chemistry. Green synthesis is employed to prepare cobalt/cellulose nanocomposites with cubic (α-cobalt) cobalt as a main component with antibacterial and magnetic properties. An in situ reduction of aqueous solutions of cobalt ions on a model cellulose substrate surface using hydrogen gas affords spherical, cellulose-stabilised cobalt nanoclusters with magnetic properties and an average diameter of 7 nm that are distributed evenly over the surface of the cellulose fibres. These cobalt/cellulose nanocomposites exhibit good antibacterial action against opportunistic pathogens both Gram-positive (S. aureus) and Gram-negative (E. coli, A. baumannii and P. aeruginosa), with zones of inhibition up to 15 mm, thereby encouraging the deployment of these advanced materials for the treatment of wastewater or within medical dressings. This method of preparation is compared with the analogous in situ reduction of cobalt ions on a cellulose surface using sodium borohydride as reducing agent

SHCal13 Southern Hemisphere calibration, 0–50,000 years cal BP

The Southern Hemisphere SHCal04 radiocarbon calibration curve has been updated with the addition of new data sets extending measurements to 2145 cal BP and including the ANSTO Younger Dryas Huon pine data set. Outside the range of measured data, the curve is based upon the Northern Hemisphere data sets as presented in IntCal13, with an interhemispheric offset averaging 43 ± 23 yr modeled by an autoregressive process to represent the short-term correlations in the offset

IFN-γ receptor and STAT1 signaling in B cells are central to spontaneous germinal center formation and autoimmunity.

Spontaneously developed germinal centers (GCs [Spt-GCs]) harbor autoreactive B cells that generate somatically mutated and class-switched pathogenic autoantibodies (auto-Abs) to promote autoimmunity. However, the mechanisms that regulate Spt-GC development are not clear. In this study, we report that B cell-intrinsic IFN-γ receptor (IFN-γR) and STAT1 signaling are required for Spt-GC and follicular T helper cell (Tfh cell) development. We further demonstrate that IFN-γR and STAT1 signaling control Spt-GC and Tfh cell formation by driving T-bet expression and IFN-γ production by B cells. Global or B cell-specific IFN-γR deficiency in autoimmune B6.Sle1b mice leads to significantly reduced Spt-GC and Tfh cell responses, resulting in diminished antinuclear Ab reactivity and IgG2c and IgG2b auto-Ab titers compared with B6.Sle1b mice. Additionally, we observed that the proliferation and differentiation of DNA-reactive B cells into a GC B cell phenotype require B cell-intrinsic IFN-γR signaling, suggesting that IFN-γR signaling regulates GC B cell tolerance to nuclear self-antigens. The IFN-γR deficiency, however, does not affect GC, Tfh cell, or Ab responses against T cell-dependent foreign antigens, indicating that IFN-γR signaling regulates autoimmune, but not the foreign antigen-driven, GC and Tfh cell responses. Together, our data define a novel B cell-intrinsic IFN-γR signaling pathway specific to Spt-GC development and autoimmunity. This novel pathway can be targeted for future pharmacological intervention to treat systemic lupus erythematosus

Developing a framework for an early warning system of seasonal temperature and rainfall tailored to aquaculture in Bangladesh

The occurrence of high temperature and heavy rain events during the monsoon season are a major climate risk affecting aquaculture production in Bangladesh. Despite the advances in the seasonal forecasting, the development of operational tools remains a challenge. This work presents the development of a seasonal forecasting approach to predict the number of warm days (NWD) and number of heavy rain days (NHRD) tailored to aquaculture in two locations of Bangladesh (Sylhet and Khulna). The approach is based on the use of meteorological and pond temperature data to generate linear models of the relationship between three-monthly temperature and rainfall statistics and NWD and NHRD, and on the evaluation of the skill of three operational dynamical models from the North American Multi-Model Ensemble (NMME) project. The linear models were used to evaluate the forecasts for two seasons and 1-month lead time: May to July (MJJ), forecast generated in April, and August to October (ASO), forecast generated in July. Differences were observed in the skill of the models predicting maximum temperature and rainfall (Spearman correlation, Root Mean Square Error, Bias statistics, and Willmott’s Index of Agreement,), in addition to NWD and NHRD from linear models, which also vary for the target seasons and location. In general, the models show higher predictive skill for NWD than NHRD, and for Sylhet than in Khulna. Among the three evaluated NMME models, CanSIPSv2 and GFDL-SPEAR exhibit the best performance, they show similar features in terms of error metrics, but CanSIPSv2 presents a lower interannual standard deviation

Nearby quasar remnants and ultra-high energy cosmic rays

As recently suggested, nearby quasar remnants are plausible sites of black-hole based compact dynamos that could be capable of accelerating ultra-high energy cosmic rays (UHECRs). In such a model, UHECRs would originate at the nuclei of nearby dead quasars, those in which the putative underlying supermassive black holes are suitably spun-up. Based on galactic optical luminosity, morphological type, and redshift, we have compiled a small sample of nearby objects selected to be highly luminous, bulge-dominated galaxies, likely quasar remnants. The sky coordinates of these galaxies were then correlated with the arrival directions of cosmic rays detected at energies $> 40$ EeV. An apparently significant correlation appears in our data. This correlation appears at closer angular scales than those expected when taking into account the deflection caused by typically assumed IGM or galactic magnetic fields over a charged particle trajectory. Possible scenarios producing this effect are discussed, as is the astrophysics of the quasar remnant candidates. We suggest that quasar remnants be also taken into account in the forthcoming detailed search for correlations using data from the Auger Observatory.Comment: 2 figures, 4 tables, 11 pages. Final version to appear in Physical Review

Individual patient data meta-analysis of trials investigating the effectiveness of intra-articular glucocorticoid injections in patients with knee or hip osteoarthritis

Based on small to moderate effect sizes for the wide range of symptomatic treatments in osteoarthritis (OA), and on the heterogeneity of OA patients, treatment guidelines for OA have stressed the need for research on clinical predictors of response to different treatments. A meta-analysis to quantify the effect modified by the predictors using individual patient data (IPD) is suggested. The initiative to collect and analyze IPD in OA research is commenced by the OA Trial Bank. The study aims are therefore: to evaluate the efficacy of intra-articular glucocorticoids for knee or hip OA in specific subgroups of patients with severe pain and (mild) inflammatory signs, over both short-term and long-term follow-up, using IPD from existing studies; to reach consensus on the rules for cooperation in a consortium; and to develop and explore the methodological issues of meta-analysis with individual OA patient data. For the current IPD analysis we will collect and synthesize IPD from randomized trials studying the effect of intra-articular glucocorticoid injections in patients with hip or knee OA. Subgroup analyses will be performed for the primary outcome of pain at both short-term and long-term follow-up, in the subgroups of patients with and without severe pain and with and without inflammatory signs. This study protocol includes the first study of the OA Trial Bank, an international collaboration that initiates meta-analyses on predefined subgroups of OA patients from existing literature. This approach ensures a widely supported initiative and is therefore likely to be successful in data collection of existing trials. The collaboration developed (that is, the OA Trial Bank) may also lead to future IPD analyses on subgroups of patients with several intervention strategies applied in OA patients

Cosmological parameters from SDSS and WMAP

We measure cosmological parameters using the three-dimensional power spectrum P(k) from over 200,000 galaxies in the Sloan Digital Sky Survey (SDSS) in combination with WMAP and other data. Our results are consistent with a ``vanilla'' flat adiabatic Lambda-CDM model without tilt (n=1), running tilt, tensor modes or massive neutrinos. Adding SDSS information more than halves the WMAP-only error bars on some parameters, tightening 1 sigma constraints on the Hubble parameter from h~0.74+0.18-0.07 to h~0.70+0.04-0.03, on the matter density from Omega_m~0.25+/-0.10 to Omega_m~0.30+/-0.04 (1 sigma) and on neutrino masses from <11 eV to <0.6 eV (95%). SDSS helps even more when dropping prior assumptions about curvature, neutrinos, tensor modes and the equation of state. Our results are in substantial agreement with the joint analysis of WMAP and the 2dF Galaxy Redshift Survey, which is an impressive consistency check with independent redshift survey data and analysis techniques. In this paper, we place particular emphasis on clarifying the physical origin of the constraints, i.e., what we do and do not know when using different data sets and prior assumptions. For instance, dropping the assumption that space is perfectly flat, the WMAP-only constraint on the measured age of the Universe tightens from t0~16.3+2.3-1.8 Gyr to t0~14.1+1.0-0.9 Gyr by adding SDSS and SN Ia data. Including tensors, running tilt, neutrino mass and equation of state in the list of free parameters, many constraints are still quite weak, but future cosmological measurements from SDSS and other sources should allow these to be substantially tightened.Comment: Minor revisions to match accepted PRD version. SDSS data and ppt figures available at http://www.hep.upenn.edu/~max/sdsspars.htm

Classification of the FRW universe with a cosmological constant and a perfect fluid of the equation of state p=wρp = w\rho

We systematically study the evolution of the Friedmann-Robertson-Walker (FRW) universe coupled with a cosmological constant $\Lambda$ and a perfect fluid that has the equation of state $p=w\rho$, where $p$ and $\rho$ denote, respectively, the pressure and energy density of the fluid, and $w$ is an arbitrary real constant. Depending on the specific values of $w,\; \Lambda$, and the curvature $k$ of 3-dimensional space, we separate all of the solutions into various cases. In each case the main properties of the evolution are given in detail, including the periods of deceleration and/or acceleration, and the existence of big bang, big crunch, and big rip singularities. In some cases, errors in classification and interpretation appearing in standard textbooks have been corrected.Comment: revtex4, 24 figure

Effects of post-capture ventilation assistance and elevated water temperature on sockeye salmon in a simulated capture-and-release experiment

The live release of wild adult Pacific salmon (Oncorhynchus spp.) following capture is a management tactic often used in commercial, aboriginal, and recreational fisheries. Fisheries capture and handling can be both exhausting and stressful to fish, which can limit their ability to swim and survive after release. As a result, researchers have assessed methods intended to improve post-release survival by assisting the flow of water over the gills of fish prior to release. Such approaches use recovery bags or boxes that direct water over the gills of restrained fish. This study evaluated a method of assisting ventilation that mimics one often employed by recreational anglers (i.e. holding fish facing into a current). Under laboratory conditions, wild Fraser River sockeye salmon (Oncorhynchus nerka) either received manual ventilation assistance for 1 min using a jet of water focused at the mouth or were left to recover unassisted following a capture-and-release simulation. A control group consisted of fish that were not exposed to the simulation or ventilation assistance. The experiment was conducted at 16 and 21°C, average and peak summer water temperatures for the Fraser River, and fish survival was monitored for 33 days. At 21°C, all fish perished within 3 days after treatment in all experimental groups, highlighting the consequences of handling adult sockeye salmon during elevated migration temperatures. Survival was higher at 16°C, with fish surviving on average 15-20 days after treatment. At 16°C, the capture-and-release simulation and ventilation assistance did not affect the survival of males; however, female survival was poor after the ventilation assistance compared with the unassisted and control groups. Our results suggest that the method of ventilation assistance tested in this study may not enhance the post-release survival of adult Fraser River sockeye salmon migrating in fresh water