Chronic thoracic hemisection spinal cord injury in adult rats induces a progressive decline in transmission from uninjured fibers to lumbar motoneurons

Although most spinal cord injuries are anatomically incomplete, only limited functional recovery has been observed in people and rats with partial lesions. To address why surviving fibers cannot mediate more complete recovery, we evaluated the physiological and anatomical status of spared fibers after unilateral hemisection (HX) of thoracic spinal cord in adult rats. We made intracellular and extracellular recordings at L5 (below HX) in response to electrical stimulation of contralateral white matter above (T6) and below (L1) HX. Responses from T6 displayed reduced amplitude, increased latency and elevated stimulus threshold in the fibers across from HX, beginning 1-2 weeks after HX. Ultrastructural analysis revealed demyelination of intact axons contralateral to the HX, with a time course similar to the conduction changes. Behavioral studies indicated partial recovery which arrested when conduction deficits began. These findings suggest a chronic pathological state in intact fibers and necessity for prompt treatment to minimize it

Information Literacy Instruction in Business Schools: Factors Affecting the Adoption of Online Library Resources by Business Students

The overall goal of this dissertation is to predict and explain how information literacy instruction (ILI) influences the adoption of online library resources (OLRs) by business students. This dissertation has two other important goals. First, this dissertation aims to assess the efficacy of active ILI and passive ILI. Second, this dissertation seeks to examine the role that OLR self-efficacy and OLR anxiety play in influencing ILI learning outcomes and the adoption of OLRs. To achieve these goals, a theoretical model was developed that integrates research on ILI outcomes and technology adoption. To test this model, a web-based survey was developed and administered to 337 business students at McMaster University. This dissertation makes several important contributions to theory. First, the findings from the analysis of the structural equation model confirm that the Technology Acceptance Model is an appropriate tool for studying the adoption of OLRs. Second, the findings indicate that amount of ILI is not a significant predictor of the adoption of OLRs. Third, though the amount of ILI was not found to be a predictor of OLR self-efficacy or OLR anxiety in the quantitative analysis, results from the qualitative analysis suggest that ILI increases self-efficacy and reduces anxiety. Fourth, the findings suggest that OLR self-efficacy and OLR anxiety are significant determinants of the adoption of OLRs where OLR self-efficacy was the strongest determinant of the adoption of OLRs. Last, consistent with Bandura’s social cognitive theory, OLR self-efficacy and OLR anxiety were found to be significantly negatively correlated; a partial mediation effect of OLR anxiety on the relationship between OLR self-efficacy and the perceived ease of use of OLRs was supported. This dissertation makes a contribution to practice by revealing that instructors should focus on delivering higher quality ILI rather than higher amounts of ILI. In particular, training interventions should be designed to promote OLR self-efficacy among business students, especially among students who have received the least amount of ILI.Doctor of Philosophy (PhD

TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 1

Immunomodulatory Function of Interleukin 28B During Primary Infection With Cytomegalovirus

Background. Feedback mechanisms between interferons α and λ (IFNs) may be affected by single nucleotide polymorphisms (SNP) in interleukin 28B (IL-28B; IFN-λ3) promoter region and may influence cytomegalovirus (CMV) replication. Methods. We associated IL-28B SNPs with the risk of CMV replication after transplantation. Next, we examined the effect of IL-28B genotypes on IL-28B, and IFN-stimulated gene (ISG) expression, and CMV replication in human foreskin fibroblast (HFF) and peripheral blood mononuclear cells (PBMCs). Results. Transplant recipients with an IL-28B SNP (rs8099917) had significantly less CMV replication (P = .036). Both HFF-cells and PBMCs with a SNP showed lower IL-28B expression during infection with CMV, but higher "antiviral” ISG expression (eg, OAS1). Fibroblasts with a SNP had a 3-log reduction of CMV replication at day 4 (P = .004). IL-28B pretreatment induced ISG expression in noninfected fibroblasts, but a relative decrease of ISG expression could be observed in CMV-infected fibroblasts. The inhibitory effects of IL-28B could be abolished by siRNA or antagonistic peptides against the IL-28 receptor. In fibroblasts, inhibition of IL-28 signaling resulted in an increase of ISG expression and 3-log reduction of CMV-replication (P = .01). Conclusions. We postulate that IL-28B may act as a key regulator of ISG expression during primary CMV infection. IL-28B SNPs may be associated with higher antiviral ISG expression, which results in better replication contro