An in Vitro Microenvironment for Nucleus Pulposus Regeneration

Intervertebral disc degeneration begins early in life, increases with age, and can ultimately result in disc failure. At the center of the disc, the nucleus pulposus (NP) resides in a hypoxic environment where degeneration is thought to begin. Initially, nucleus pulposus cells (NPCs) display altered morphology and function, along with increased rates of cellular senescence and apoptosis. Though no widely accepted treatment exists, autologous NP implantation techniques have shown promise. However, the process is flawed as a result of the long in vitro expansion required to obtain sufficient numbers of cells. Prolonged expansion on plastic produces negative changes such as loss of the NP phenotype and reduced redifferentiation ability. Because cell based tissue engineering techniques require a metabolically active population of cells, stem cells have attracted attention for regenerative NP strategies due to their self-renewal ability and multipotent differentiation capacity. Specifically, synovium derived stem cells (SDSCs) have a higher chondrogenic capacity compared to stem cells derived from other tissues. Another advantage and potential use of SDSCs is that they can produce decellularized extracellular matrix (DECM); expansion of SDSCs or NPCs on this substrate can dramatically increase the rates of proliferation, delay senescence associated changes, and support chondrogenic activity upon induction. In this study, it was determined that NPCs alone and NPCs in co-culture with SDSCs can produce their own unique DECM. It was determined that DECM properties may be modulated by varying oxygen tension during DECM deposition. While the DECM deposited by NPCs along with SDSCs improved proliferation and guided SDSC differentiation towards the NP lineage, the effect was greater than NPC derived DECM and comparable to SDSC derived DECM. Normoxic conditions during DECM preparation were more beneficial to cell proliferation, but hypoxic conditions promoted differentiation towards the NP lineage. Finally, hypoxic conditions during pellet culture promoted NPC viability and redifferentiation. Low oxygen combined with DECM can facilitate cell-based NP regeneration

Lightweight Composite Materials for Heavy Duty Vehicles

The main objective of this project is to develop, analyze and validate data, methodologies and tools that support widespread applications of automotive lightweighting technologies. Two underlying principles are guiding the research efforts towards this objective: • Seamless integration between the lightweight materials selected for certain vehicle systems, cost-effective methods for their design and manufacturing, and practical means to enhance their durability while reducing their Life-Cycle-Costs (LCC). • Smooth migration of the experience and findings accumulated so far at WVU in the areas of designing with lightweight materials, innovative joining concepts and durability predictions, from applications to the area of weight savings for heavy vehicle systems and hydrogen storage tanks, to lightweighting applications of selected systems or assemblies in light–duty vehicles

Current considerations for clinical management and care of non-alcoholic fatty liver disease: Insights from the 1st International Workshop of the Canadian NASH Network (CanNASH).

Non-alcoholic fatty liver disease (NAFLD) affects approximately 8 million Canadians. NAFLD refers to a disease spectrum ranging from bland steatosis to non-alcoholic steatohepatitis (NASH). Nearly 25% of patients with NAFLD develop NASH, which can progress to liver cirrhosis and related end-stage complications. Type 2 diabetes and obesity represent the main risk factors for the disease. The Canadian NASH Network is a national collaborative organization of health care professionals and researchers with a primary interest in enhancing understanding, care, education, and research around NAFLD, with a vision of best practices for this disease state. At the 1st International Workshop of the CanNASH network in April 2021, a joint event with the single topic conference of the Canadian Association for the Study of the Liver (CASL), clinicians, epidemiologists, basic scientists, and community members came together to share their work under the theme of NASH. This symposium also marked the initiation of collaborations between Canadian and other key opinion leaders in the field representative of international liver associations. The main objective is to develop a policy framework that outlines specific targets, suggested activities, and evidence-based best practices to guide provincial, territorial, and federal organizations in developing multidisciplinary models of care and strategies to address this epidemic

Endogenous antigen processing drives the primary CD4+ T cell response to influenza.

By convention, CD4+ T lymphocytes recognize foreign and self peptides derived from internalized antigens in combination with major histocompatibility complex class II molecules. Alternative pathways of epitope production have been identified, but their contributions to host defense have not been established. We show here in a mouse infection model that the CD4+ T cell response to influenza, critical for durable protection from the virus, is driven principally by unconventional processing of antigen synthesized within the infected antigen-presenting cell, not by classical processing of endocytosed virions or material from infected cells. Investigation of the cellular components involved, including the H2-M molecular chaperone, the proteasome and γ-interferon-inducible lysosomal thiol reductase revealed considerable heterogeneity in the generation of individual epitopes, an arrangement that ensures peptide diversity and broad CD4+ T cell engagement. These results could fundamentally revise strategies for rational vaccine design and may lead to key insights into the induction of autoimmune and anti-tumor responses

Mitochondrial and Plasma Membrane Pools of Stomatin-Like Protein 2 Coalesce at the Immunological Synapse during T Cell Activation

Stomatin-like protein 2 (SLP-2) is a member of the stomatin – prohibitin – flotillin – HflC/K (SPFH) superfamily. Recent evidence indicates that SLP-2 is involved in the organization of cardiolipin-enriched microdomains in mitochondrial membranes and the regulation of mitochondrial biogenesis and function. In T cells, this role translates into enhanced T cell activation. Although the major pool of SLP-2 is associated with mitochondria, we show here that there is an additional pool of SLP-2 associated with the plasma membrane of T cells. Both plasma membrane-associated and mitochondria-associated pools of SLP-2 coalesce at the immunological synapse (IS) upon T cell activation. SLP-2 is not required for formation of IS nor for the re-localization of mitochondria to the IS because SLP-2-deficient T cells showed normal re-localization of these organelles in response to T cell activation. Interestingly, upon T cell activation, we found the surface pool of SLP-2 mostly excluded from the central supramolecular activation complex, and enriched in the peripheral area of the IS where signalling TCR microclusters are located. Based on these results, we propose that SLP-2 facilitates the compartmentalization not only of mitochondrial membranes but also of the plasma membrane into functional microdomains. In this latter location, SLP-2 may facilitate the optimal assembly of TCR signalosome components. Our data also suggest that there may be a net exchange of membrane material between mitochondria and plasma membrane, explaining the presence of some mitochondrial proteins in the plasma membrane

Closed-form controlled invariant sets for pedestrian avoidance

The recent trends in the automotive industry towards autonomous vehicles bring the problem of pedestrian avoidance to the forefront of a long list of safety concerns. In this paper we propose a closed-form solution to this problem by explicitly computing closed-form expressions for subsets of the state space where an autonomous vehicle is guaranteed to avoid collisions with a pedestrian. These sets, being controlled invariant, immediately lead to control laws for pedestrian avoidance