Anatomy of autoantibody production: Dominant localization of antibody-producing cells to T cell zones in fas-deficient mice

AbstractThe goal of this study was to examine the in vivo site of autoantibody production in normal and autoimmune-prone mice. B cells were identified in tissue sections with IgM- and IgG2a-specific riboprobes that readily distinguished resting cells from antibody-forming cells (AFC). In normal mice, the few identifiable IgG2a-secreting cells were found in the red pulp. By contrast, in Ipr mice exceedingly high numbers of IgG2a and autoantibody-producing cells were found deep within the T cell-rich periarteriolar lymphoid sheaths (PALS). This unusual anatomic location of autoantibody-secreting B cells is unique to Fas dysregulated strains, since IgG2a-producing cells in MRL/+ and (SWR × NZB)F1 mice were found predominantly in the red pulp or outer PALS, similar to normal mice. Furthermore, analysis of spleens from Ipr and non-Ipr anti-DNA immunoglobulin transgenic mice revealed dramatic accumulation of Tg+ cells in the inner PALS only in Ipr mice. These data suggest that in the absence of Fas, autoreactive B cells accumulate in T cell-rich zones, and this anatomic feature may contribute to autoantibody production

Lessons from America: teaching politics with the Google generation

The superabundance of information available, particularly through the internet, is posing many challenges to the traditional pedagogy of higher education. Much of this concern is focused on the ubiquity of the search engine Google, with Tara Brabazon amongst the most conspicuous to claim that ‘the popularity of Google is facilitating laziness, poor scholarship and compliant thinking’ (Brabazon, 2007: 15). At the very least, it is clear that Google – as well as the more specialist Google Scholar and the (mostly) open-edited online encyclopedia Wikipedia – have quickly established prominent positions in many students’ strategies to locate information for various assignments. This has led to particular cohorts of students being dubbed, often in a derogatory fashion, the Google generation. While making it clear that many of the stereotypical claims made on behalf of this group are unfounded, this paper will present evidence to support some of the concerns made by Brabazon and others. In addition, it will define the concept that many have recognised as the potential solution to this problem, and will examine one ambitious attempt from the US to confront these problems directly. Moreover, it will be argued that adoption of similar strategies in the UK might address some important criticisms levelled at general university-level politics education in this country

Toxoplasma gondii is not an important contributor to poor reproductive performance of primiparous ewes from southern Australia: A prospective cohort study

Background Toxoplasma gondii causes reproductive losses in sheep worldwide, including Australia. The reproductive performance of primiparous ewes is typically lower than for mature, multiparous ewes, and younger ewes are more likely to be immunologically naïve and therefore more susceptible to reproductive disease if T. gondii infection occurs during pregnancy. The aim of this study was to assess the impact of infection with T. gondii on the reproductive performance of primiparous ewes in southern Australia using a prospective cohort study. This will inform the need for targeted control strategies for T. gondii in Australian sheep. Results Toxoplasma gondii seropositivity using indirect ELISA was detected at 16/28 farms located across southern Australia. Apparent seropositivity to T. gondii was lower in primiparous ewes (1.1, 95% confidence interval (CI) 0.6, 1.8) compared to mature, multiparous ewes (8.1, 95% CI 6.0, 10.5; P < 0.001). Toxoplasma gondii seroconversion during the gestation and lambing period was confirmed for 11/1097 (1.0, 95% CI 0.5, 1.7) of pregnant primiparous ewes that failed to raise a lamb, and 1/161 (0.6, 95% CI 0.1, 2.9) primiparous ewes with confirmed mid-pregnancy abortion. Conclusions Low frequency of detection of T. gondii seroconversion during gestation and low frequency of seropositivity to T. gondii suggests that toxoplasmosis was not an important contributor to reproductive losses in primiparous ewes on farms located over a wide geographical area in southern Australia

Peeling back the layers: Deconstructing information literacy discourse in higher education

The discourses of information literacy practice create epistemological assumptions about how the practice should happen, who should be responsible and under what conditions instruction should be given. Analysis of a wide range of documents and texts emerging from the Higher Education (HE) sector suggest that information literacy (IL) is shaped by two competing and incongruent narratives. The outward facing narrative of information literacy (located in information literacy standards and guidelines) positions information literacy as an empowering practice that arms students with the knowledge and skills to battle the complexity of the modern information world. In contrast, the inward facing narrative (located in information literacy texts) positions students as lacking appropriate knowledge, skills and agency. This deficit perception, which has the capacity to influence pedagogical practice, is at odds with constructivist and action-oriented views that are espoused within information literacy instructional pedagogy. This presentation represents the first paper in a research programme that interrogates the epistemological premises and discourses of information literacy within HE

Regulation and Function of the Interleukin 13 Receptor α 2 During a T Helper Cell Type 2–dominant Immune Response

Highly polarized type 2 cytokine responses can be harmful and even lethal to the host if they are too vigorous or persist too long. Therefore, it is important to elucidate the mechanisms that down-regulate these reactions. Interleukin (IL)-13 has emerged as a central mediator of T helper cell (Th)2-dominant immune responses, exhibiting a diverse array of functional activities including regulation of airway hyperreactivity, resistance to nematode parasites, and tissue remodeling and fibrosis. Here, we show that IL-13 receptor (R)α2 is a critical down-regulatory factor of IL-13–mediated tissue fibrosis induced by the parasitic helminth Schistosoma mansoni. IL-13Rα2 expression was induced after the onset of the fibrotic response, IL-10, IL-13, and Stat6 dependent, and inhibited by the Th1-inducing adjuvant IL-12. Strikingly, schistosome-infected C57BL/6 and BALB/c IL-13Rα2–deficient mice showed a marked exacerbation in hepatic fibrosis, despite displaying no change in granuloma size, tissue eosinophilia, or mastocytosis. Fibrosis increased despite the fact that IL-13 levels decreased significantly in the liver and serum. Importantly, pathology was prevented when IL-13Rα2–deficient mice were treated with a soluble IL-13Rα2-Fc construct, formally demonstrating that their exacerbated fibrotic response was due to heightened IL-13 activity. Together, these studies illustrate the central role played by the IL-13Rα2 in the down-regulation of a chronic and pathogenic Th2-mediated immune response

Fasting increases microbiome-based colonization resistance and reduces host inflammatory responses during an enteric bacterial infection.

We thank BC Children’s Hospital Research Institute (BCCHR) animal facility staff as well as the BCCHR histology core for their assistance. We thank Ms. Caixia Ma for assistance with animal handling. We thank Gut4Health for assistance with microbiome analysis and the rest of the Vallance lab for feedback and valuable discussions. We thank Dr. Jose Puente and Ms. Carmen Contreras for generating the luciferase reporter construct and Dr. Leigh Knodler for helpful discussions.Peer reviewe

WIYN Open Cluster Study. XXXIX. Abundances in NGC 6253 from HYDRA Spectroscopy of the Li 6708 A Region

High-dispersion spectra of 89 potential members of the old, super-metal-rich open cluster, NGC 6253, have been obtained with the HYDRA multi-object spectrograph. Based upon radial-velocity measurements alone, 47 stars at the turnoff of the cluster color-magnitude diagram (CMD) and 18 giants are identified as potential members. Five turnoff stars exhibit evidence of binarity while proper-motion data eliminates two of the dwarfs as members. The mean cluster radial velocity from probable single-star members is -29.4 +/- 1.3 km/sec (sd). A discussion of the current estimates for the cluster reddening, derived independently of potential issues with the BV cluster photometry, lead to an adopted reddening of E(B-V) = 0.22 +/- 0.04. From equivalent width analyses of 38 probable single-star members near the CMD turnoff, the weighted average abundances are found to be [Fe/H] = +0.43 +/- 0.01, [Ni/H] = +0.53 +/- 0.02 and [Si/H] = +0.43 (+0.03,-0.04), where the errors refer to the standard errors of the weighted mean. Weak evidence is found for a possible decline in metallicity with increasing luminosity among stars at the turnoff. We discuss the possibility that our turnoff stars have been affected by microscopic diffusion. For 15 probable single-star members among the giants, spectrum synthesis leads to abundances of +0.46 (+0.02,-0.03) for [Fe/H]. While less than half the age of NGC 6791, NGC 6253 is at least as metal-rich and, within the uncertainties, exhibits the same general abundance pattern as that typified by super-metal-rich dwarfs of the galactic bulge.Comment: 5 Tables, 9 figures, 45 page

Geometrodynamics of Variable-Speed-of-Light Cosmologies

This paper is dedicated to the memory of Dennis Sciama. Variable-Speed-of-Light (VSL) cosmologies are currently attracting interest as an alternative to inflation. We investigate the fundamental geometrodynamic aspects of VSL cosmologies and provide several implementations which do not explicitly break Lorentz invariance (no "hard" breaking). These "soft" implementations of Lorentz symmetry breaking provide particularly clean answers to the question "VSL with respect to what?". The class of VSL cosmologies we consider are compatible with both classical Einstein gravity and low-energy particle physics. These models solve the "kinematic" puzzles of cosmology as well as inflation does, but cannot by themselves solve the flatness problem, since in their purest form no violation of the strong energy condition occurs. We also consider a heterotic model (VSL plus inflation) which provides a number of observational implications for the low-redshift universe if chi contributes to the "dark energy" either as CDM or quintessence. These implications include modified gravitational lensing, birefringence, variation of fundamental constants and rotation of the plane of polarization of light from distant sources.Comment: 19 pages, latex 209, revtex 3.1; To appear in Physical Review D; Numerous small changes of presentation and emphasis; new section on the entropy problem; references updated; central results unaffecte

Phase 1B, randomized, double-blind, dose-escalation trial of CPG 10101 in patients with chronic hepatitis C virus

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