Social cognition in multiple sclerosis:A systematic review and meta-analysis

Objective: To quantify the magnitude of deficits in theory of mind (ToM) and facial emotion recognition among patients with multiple sclerosis (MS) relative to healthy controls. Methods: An electronic database search of Ovid MEDLINE, PsycINFO, and Embase was conducted from inception to April 1, 2016. Eligible studies were original research articles published in peer-reviewed journals that examined ToM or facial emotion recognition among patients with a diagnosis of MS and a healthy control comparison group. Data were independently extracted by 2 authors. Effect sizes were calculated using Hedges g. Results: Twenty-one eligible studies were identified assessing ToM (12 studies) and/or facial emotion recognition (13 studies) among 722 patients with MS and 635 controls. Deficits in both ToM (g -0.71, 95% confidence interval [CI] -0.88 to -0.55, p < 0.001) and facial emotion recognition (g -0.64, 95% CI -0.81 to -0.47, p < 0.001) were identified among patients with MS relative to healthy controls. The largest deficits were observed for visual ToM tasks and for the recognition of negative facial emotional expressions. Older age predicted larger emotion recognition deficits. Other cognitive domains were inconsistently associated with social cognitive performance. Conclusions: Social cognitive deficits are an overlooked but potentially important aspect of cognitive impairment in MS with potential prognostic significance for social functioning and quality of life. Further research is required to clarify the longitudinal course of social cognitive dysfunction, its association with MS disease characteristics and neurocognitive impairment, and the MS-specific neurologic damage underlying these deficits

The Burkholderia cenocepacia Type VI Secretion System Effector TecA Is a Virulence Factor in Mouse Models of Lung Infection

Burkholderia cenocepacia is a member of the Burkholderia cepacia complex (Bcc), a group of bacteria with members responsible for causing lung infections in cystic fibrosis (CF) patients. The most severe outcome of Bcc infection in CF patients is cepacia syndrome, a disease characterized by necrotizing pneumonia with bacteremia and sepsis. B. cenocepacia is strongly associated with cepacia syndrome, making it one of the most virulent members of the Bcc. Mechanisms underlying the pathogenesis of B. cenocepacia in lung infections and cepacia syndrome remain to be uncovered. B. cenocepacia is primarily an intracellular pathogen and encodes the type VI secretion system (T6SS) effector TecA, which is translocated into host phagocytes. TecA is a deamidase that inactivates multiple Rho GTPases, including RhoA. Inactivation of RhoA by TecA triggers assembly of the pyrin inflammasome, leading to secretion of proinflammatory cytokines, such as interleukin-1b, from macrophages. Previous work with the B. cenocepacia clinical isolate J2315 showed that TecA increases immunopathology during acute lung infection in C57BL/6 mice and suggested that this effector acts as a virulence factor by triggering assembly of the pyrin inflammasome. Here, we extend these results using a second B. cenocepacia clinical isolate, AU1054, to demonstrate that TecA exacerbates weight loss and lethality during lung infection in C57BL/6 mice and mice engineered to have a CF genotype. Unexpectedly, pyrin was dispensable for TecA virulence activity in both mouse infection models. Our findings establish that TecA is a B. cenocepacia virulence factor that exacerbates lung inflammation, weight loss, and lethality in mouse infection models. IMPORTANCE B. cenocepacia is often considered the most virulent species in the Bcc because of its close association with cepacia syndrome in addition to its capacity to cause chronic lung infections in CF patients (1). Prior to the current study, virulence factors of B. cenocepacia important for causing lethal disease had not been identified in a CF animal model of lung infection. Results of this study describe a CF mouse model and its use in demonstrating that the T6SS effector TecA of B. cenocepacia exacerbates inflammatory cell recruitment and weight loss and is required for lethality and, thus, acts as a key virulence factor during lung infection. This model will be important in further studies to better understand TecA’s role as a virulence factor and in investigating ways to prevent or treat B. cenocepacia infections in CF patients. Additionally, TecA may be the founding member of a family of virulence factors in opportunistic pathogens

Spectroscopy of Broad Line Blazars from 1LAC

We report on optical spectroscopy of 165 Flat Spectrum Radio Quasars (FSRQs) in the Fermi 1LAC sample, which have helped allow a nearly complete study of this population. Fermi FSRQ show significant evidence for non-thermal emission even in the optical; the degree depends on the gamma-ray hardness. They also have smaller virial estimates of hole mass than the optical quasar sample. This appears to be largely due to a preferred (axial) view of the gamma-ray FSRQ and non-isotropic (H/R ~ 0.4) distribution of broad-line velocities. Even after correction for this bias, the Fermi FSRQ show higher mean Eddington ratios than the optical population. A comparison of optical spectral properties with Owens Valley Radio Observatory radio flare activity shows no strong correlation.Comment: Accepted for publication in Ap

The Prodomain of the Bordetella Two-Partner Secretion Pathway Protein FhaB Remains Intracellular yet Affects the Conformation of the Mature C-terminal Domain

Two-Partner Secretion (TPS) systems use β-barrel proteins of the Omp85-TpsB superfamily to transport large exoproteins across the outer membranes of Gram-negative bacteria. The Bordetella FHA/FhaC proteins are prototypical of TPS systems in which the exoprotein contains a large C-terminal prodomain that is removed during translocation. Although it is known that the FhaB prodomain is required for FHA function in vivo, its role in FHA maturation has remained mysterious. We show here that the FhaB prodomain is required for the extracellularly-located mature C-terminal domain (MCD) of FHA to achieve its proper conformation. We show that the C-terminus of the prodomain is retained intracellularly and that sequences within the N-terminus of the prodomain are required for this intracellular localization. We also identify sequences at the C-terminus of the MCD that are required for release of mature FHA from the cell surface. Our data support a model in which the intracellularly-located prodomain affects the final conformation of the extracellularly-located MCD, which, we hypothesize, triggers cleavage and degradation of the prodomain