Molecule Microscopy

Contains research objectives and reports on seven research projects.Whitaker Health Sciences FundFrancis L. Friedman ChairNational Institutes of Health (Grant AM-31546)National Institutes of Health (Grant AM-25535)International Business Machines, Inc

Molecular Physics

Contains reports on two research projects.F.L. Freidman ChairNational Institutes of Health (Grant AM 25535)Whitaker FoundationInternational Business Machines, Inc

Molecule Microscopy

Contains research objectives and reports on four research projects.National Institutes of Health (Grant AM-25535)Whitaker FoundationFrancis L. Friedman Chai

Low 2-Dimensional CD4 T Cell Receptor Affinity for Myelin Sets in Motion Delayed Response Kinetics

T cells recognizing self-peptides that mediate autoimmune disease and those that are responsible for efficacious immunity against pathogens may differ in affinity for antigen due to central and peripheral tolerance mechanisms. Here we utilize prototypical self-reactive (myelin) and viral-specific (LCMV) T cells from T cell receptor (TCR) transgenic mice (2D2 and SMARTA, respectively) to explore affinity differences. The T cells responsive to virus possessed >10,000 fold higher 2D affinity as compared to the self-reactive T cells. Despite their dramatically lower affinity for their cognate ligand, 2D2 T cells respond with complete, albeit delayed, activation (proliferation and cytokine production). SMARTA activation occurs rapidly, achieving peak phosphorylation of p38 (1 minute), Erk (30 minutes), and Jun (3 hours) as well as CD69 and CD25 upregulation (3 and 6 hours, respectively), with a corresponding early initiation of proliferation. 2D2 stimulation with MOG results in altered signaling – no phospho-Erk or phospho-p38 accumulation, significantly delayed activation kinetics of Jun (12 hours), and delayed but sustained SHP-1 activity – as well as delayed CD69 and CD25 expression (12–24 hours), and slow initiation of proliferation. This delay was not intrinsic to the 2D2 T cells, as a more potent antigen with >100-fold increased 2D affinity restored rapid response kinetics in line with those identified for the viral antigen. Taken together, these data demonstrate that time can offset low TCR affinity to attain full activation and suggest a mechanism by which low affinity T cells participate in autoimmune disease

Neutrality of Molecules by the Pulsed Gas Flow Method

Contains an introduction and a description on one research project.F.L. Friedman Chai

The Grizzly, February 7, 2019

Dean Nolan Recalls her 33 Year Career at Ursinus • Berman Exhibits Spotlight Opioid Crisis, Patriarchy • Senior Alumni Award: Its History and Value • Rhiannon Giddens to be 2019 Commencement Speaker • Inclusive Community Grant Awardees Announced • Externship Profile: Christopher Karmilowicz Explores the World of Finance • Opinions: U.S. Should Keep its Hands Off Venezuela; The Opioid Crisis: Widespread and Institutional • Men\u27s Hoops Upsets #10 Swarthmore; Williams Jr. Earns CC Player of the Week • Konstanzer Joins 1,000 Point Clubhttps://digitalcommons.ursinus.edu/grizzlynews/1611/thumbnail.jp

Factors associated with remission of post-traumatic brain injury fatigue in the years following traumatic brain injury (TBI): a TBI model systems module study

Post-traumatic brain injury fatigue (PTBIF) is a major problem in the years after traumatic brain injury (TBI), yet little is known about its persistence and resolution. The objective of the study was to identify factors related to PTBIF remission and resolution. TBI Model System registrants at five centres participated in interviews at either one and two years post-injury (Y1-2 Cohort), or two and five years post-injury (Y2-5 Cohort). Characteristics of participants with PTBIF remission were compared to those with PTBIF persistence. Variables studied included the presence of and changes in disability, sleep dysfunction, mood, and community participation. The Functional Independence Measure did not differ significantly between groups or over time. In the Y1-2 Cohort the Fatigue Resolved group scored significantly better on the Disability Rating Scale and Pittsburgh Sleep Quality Index. In the Y2-5 Cohort the Fatigue Resolved group scored significantly higher on a measure of community participation. It was concluded that fewer than half of the sample in each cohort experienced a remission of PTBIF between time points. Persistence of PTBIF 1–2 years post-injury is associated with disability, sleep disturbance, and depression while persistence of fatigue beyond 2 years post-injury appears to be related to participation level, underscoring the potential impact of effective surveillance, assessment, and treatment of this condition in optimising life after TBI. Differences in fatigue progression may point to the presence of different types of PTBIF