Life Sciences Commons^™

Natural Autoantibodies: Origin, Function And Utility For Diagnosis Of Disease, Abhirup Sarkar

Graduate School of Biomedical Sciences Theses and Dissertations

Autoantibodies (aAbs) by the simplest definitions have been described as antibodies against self-antigens and were exclusively associated with autoimmune diseases. Eventually, studies demonstrated that they are abundant in the blood of all human sera, regardless of age, gender, or the presence or absence of disease, and were thus named as ‘natural autoantibodies’. The underlying reason for their ubiquity has remained elusive, but we have hypothesized that they are responsible for clearing blood-borne cell and tissue debris generated under conditions of health and disease. To test this, we chose to use two widely different disease model systems, namely neurodegenerative diseases and …

Cyclin C Regulated Oxidative Stress Responsive Transcriptome In Mus Musculus Embryonic Fibroblasts, David C Stieg, Kai-Ti Chang, Katrina F Cooper, Randy Strich

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

The transcriptional changes that occur in response to oxidative stress help direct the decision to maintain cell viability or enter a cell death pathway. Cyclin C-Cdk8 is a conserved kinase that associates with the RNA polymerase II Mediator complex that stimulates or represses transcription depending on the locus. In response to oxidative stress, cyclin C, but not Cdk8, displays partial translocation into the cytoplasm. These findings open the possibility that cyclin C relocalization is a regulatory mechanism governing oxidative stress-induced transcriptional changes. In the present study, the cyclin C-dependent transcriptome was determined and compared to transcriptional changes occurring in oxidatively …

Visual And Verbal Serial List Learning In Patients With Statistically-Determined Mild Cognitive Impairment., Victor Wasserman, Sheina Emrani, Emily F Matusz, David Miller, Kelly Davis Garrett, Katherine A Gifford, Timothy J Hohman, Angela L Jefferson, Rhoda Au, Rod Swenson, David J Libon, Consortium For Clinical And Epidemiological Neuropsychological Data Analysis (Cenda).

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Background and Objective: Prior research with patients with mild cognitive impairment (MCI) suggests that visual versus verbal episodic memory test performance may be more sensitive to emergent illness. However, little research has examined visual versus verbal episodic memory performance as related to MCI subtypes.

Research Design and Methods: Patients were diagnosed with non-MCI, amnestic MCI (aMCI), and combined mixed/dysexecutive MCI (mixed/dys MCI). Visual and verbal episodic memory were assessed with the Brief Visuospatial Memory Test-Revised (BVMT-R) and the 12-word Philadelphia (repeatable) Verbal Learning Test (P[r]VLT), respectively.

Results: BVMT-R and P(r)VLT scores yielded similar between-group patterns of performance. Non-MCI patients scored …

Yeast Mitochondrial Protein Pet111p Binds Directly To Two Distinct Targets In Cox2 Mrna, Suggesting A Mechanism Of Translational Activation, Julia L Jones, Katharina B Hofmann, Andrew T Cowan, Dmitry Temiakov, Patrick Cramer, Michael Anikin

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

The genes in mitochondrial DNA code for essential subunits of the respiratory chain complexes. In yeast, expression of mitochondrial genes is controlled by a group of gene-specific translational activators encoded in the nucleus. These factors appear to be part of a regulatory system that enables concerted expression of the necessary genes from both nuclear and mitochondrial genomes to produce functional respiratory complexes. Many of the translational activators are believed to act on the 5'-untranslated regions of target mRNAs, but the molecular mechanisms involved in this regulation remain obscure. In this study, we used a combination of in vivo and in …

A Mathematical Investigation On Tumor-Immune Dynamics: The Impact Of Vaccines On The Immune Response, Jonathan Quinonez, Neethi Dasu, Mahboobi Qureshi

Rowan-Virtua Research Day

Mathematical models analyzing tumor-immune interactions provide a framework by which to address specific scenarios in regard to tumor-immune dynamics. Important aspects of tumor-immune surveillance to consider is the elimination of tumor cells from a host’s cell-mediated immunity as well as the implications of vaccines derived from synthetic antigen. In present studies, our mathematical model examined the role of synthetic antigen to the strength of the immune system. The constructed model takes into account accepted knowledge of immune function as well as prior work done by de Pillis et al. All equations describing tumor-immune growth, antigen presentation, immune response, and interaction …

Repetitive Mild Traumatic Brain Injury Impairs Performance In A Rodent Assay Of Cognitive Flexibility, Christopher P. Knapp, Doug P. Fox, Ramesh Raghupathi, Laura L. Giacometti, Stan B. Floresco, Barry D. Waterhouse, Rachel L. Navarra

Rowan-Virtua Research Day

Mild traumatic brain injury (mTBI) occurs in almost 80% of the 3 million reported cases of TBI-related emergency department visits each year in the United States. The majority of mTBIs, sometimes classified as concussions, are due to sports-related activities and typically occur repeatedly over the course of an athlete’s career. mTBI symptoms are generally classified as either somatic or neuropsychiatric/cognitive in nature and include impairments in prefrontal cortex mediated functions, including attention, memory, processing speed, reaction times, problem solving, and cognitive flexibility. To date, there remains a major gap in our understanding of the behavioral manifestations, underlying neurobiology, and treatment …

Cyclin C: The Story Of A Non-Cycling Cyclin., Jan Ježek, Daniel G J Smethurst, David C Stieg, Z A C Kiss, Sara E Hanley, Vidyaramanan Ganesan, Kai-Ti Chang, Katrina F Cooper, Randy Strich

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

The class I cyclin family is a well-studied group of structurally conserved proteins that interact with their associated cyclin-dependent kinases (Cdks) to regulate different stages of cell cycle progression depending on their oscillating expression levels. However, the role of class II cyclins, which primarily act as transcription factors and whose expression remains constant throughout the cell cycle, is less well understood. As a classic example of a transcriptional cyclin, cyclin C forms a regulatory sub-complex with its partner kinase Cdk8 and two accessory subunits Med12 and Med13 called the Cdk8-dependent kinase module (CKM). The CKM reversibly associates with the multi-subunit …

Antibodies In The Diagnosis, Prognosis, And Prediction Of Psychotic Disorders., Thomas A Pollak, Jonathan P Rogers, Robert G Nagele, Mark Peakman, James M Stone, Anthony S David, Philip Mcguire

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Blood-based biomarker discovery for psychotic disorders has yet to impact upon routine clinical practice. In physical disorders antibodies have established roles as diagnostic, prognostic and predictive (theranostic) biomarkers, particularly in disorders thought to have a substantial autoimmune or infective aetiology. Two approaches to antibody biomarker identification are distinguished: a "top-down" approach, in which antibodies to specific antigens are sought based on the known function of the antigen and its putative role in the disorder, and emerging "bottom-up" or "omics" approaches that are agnostic as to the significance of any one antigen, using high-throughput arrays to identify distinctive components of the …