Processing of proteins in autophagy vesicles of antigen-presenting cells generates citrullinated peptides recognized by the immune system

Our laboratory has been investigating for some time the nature of the response of T lymphocytes in autoimmunity in the reactions against self-proteins that result in a number of diseases, such as type 1 diabetes, multiple sclerosis, rheumatoid arthritis (RA) and others. T cells recognize peptides generated from proteins that are processed by antigen-presenting cells (APC). The peptides may derive from exogenous proteins or from the normal catabolism of self-proteins. The peptides complexed to major histocompatibility complex (MHC) molecules constitute the chemical entity that is engaged by the antigen-receptor of T cells. An important hypothesis postulates that self-peptides that suffer post-translational modifications in the APC may form neo-antigens that are recognized by the immune system and form the target of autoimmunity. Our interest in citrullination in the context of antigen processing and presentation stemmed from studies suggesting that an immune response to citrullinated self-peptides may be involved in autoimmunity. In a first publication, we found T cells that specifically recognized citrullinated peptides after immunization of inbred mice with standard foreign proteins. We used the small protein hen-egg white lysozyme. These T cells only recognized the citrullinated peptide and not the unmodified one, thus proving that a neo-epitope had been created by this modification. But how this modification took place was not known. Our recent report describes a central role for autophagy in citrullination of peptides by APC.     

Protein Tyrosine Phosphatase PTP1B Is Involved in Hippocampal Synapse Formation and Learning

ER-bound PTP1B is expressed in hippocampal neurons, and accumulates among neurite contacts. PTP1B dephosphorylates ß-catenin in N-cadherin complexes ensuring cell-cell adhesion. Here we show that endogenous PTP1B, as well as expressed GFP-PTP1B, are present in dendritic spines of hippocampal neurons in culture. GFP-PTP1B overexpression does not affect filopodial density or length. In contrast, impairment of PTP1B function or genetic PTP1B-deficiency leads to increased filopodia-like dendritic spines and a reduction in mushroom-like spines, while spine density is unaffected. These morphological alterations are accompanied by a disorganization of pre- and post-synapses, as judged by decreased clustering of synapsin-1 and PSD-95, and suggest a dynamic synaptic phenotype. Notably, levels of ß-catenin-Tyr-654 phosphorylation increased ∼5-fold in the hippocampus of adult PTP1B^−/− (KO) mice compared to wild type (WT) mice and this was accompanied by a reduction in the amount of ß-catenin associated with N-cadherin. To determine whether PTP1B-deficiency alters learning and memory, we generated mice lacking PTP1B in the hippocampus and cortex (PTP1B^fl/fl–Emx1-Cre). PTP1B^fl/fl–Emx1-Cre mice displayed improved performance in the Barnes maze (decreased time to find and enter target hole), utilized a more efficient strategy (cued), and had better recall compared to WT controls. Our results implicate PTP1B in structural plasticity within the hippocampus, likely through modulation of N-cadherin function by ensuring dephosphorylation of ß-catenin on Tyr-654. Disruption of hippocampal PTP1B function or expression leads to elongation of dendritic filopodia and improved learning and memory, demonstrating an exciting novel role for this phosphatase.     

Weather impacts on leisure activities in Halifax,Nova Scotia

The aim of this study was to investigate the impact of daily atmospheric weather conditions on daily leisure activity engagement, with a focus on physically active leisure. The methods capitalize on time diary data that were collected in Halifax, Nova Scotia to calculate objective measures of leisure activity engagement. Daily meteorological data from Environment Canada and daily sunrise and sunset times from the National Research Council of Canada are used to develop objective measures of the natural atmospheric environment. The time diary data were merged with the meteorological data in order to quantify the statistical association between daily weather conditions and the type, participation rate, frequency, and duration of leisure activity engagement. The results indicate that inclement and uncomfortable weather conditions, especially relating to thermal comfort and mechanical comfort, pose barriers to physically active leisure engagement, while promoting sedentary and home-based leisure activities. Overall, daily weather conditions exhibit modest, but significant, effects on leisure activity engagement; the strongest associations being for outdoor active sports and outdoor active leisure time budgets. In conclusion, weather conditions influence the type, participation rate, frequency, and duration of leisure activity engagement, which is an important consideration for health-promotion programming.     

Maneuvering and stability performance of a robotic tuna

The Draper Laboratory Vorticity Control Unmanned Undersea Vehicle(VCUUV) is the first mission-scale, autonomous underwater vehiclethat uses vorticity control propulsion and maneuvering. Builtas a research platform with which to study the energetics andmaneuvering performance of fish-swimming propulsion, the VCUUVis a self-contained free swimming research vehicle which followsthe morphology and kinematics of a yellowfin tuna. The forwardhalf of the vehicle is comprised of a rigid hull which housesbatteries, electronics, ballast and hydraulic power unit. Theaft section is a freely flooded articulated robot tail whichis terminated with a lunate caudal fin. Utilizing experimentallyoptimized body and tail kinematics from the MIT RoboTuna, theVCUUV has demonstrated stable steady swimming speeds up to 1.2m/sec and aggressive maneuvering trajectories with turning ratesup to 75 degrees per second. This paper summarizes the vehiclemaneuvering and stability performance observed in field trialsand compares the results to predicted performance using theoreticaland empirical techniques.