Abstract Competition

Articlehttp://deepblue.lib.umich.edu/bitstream/2027.42/97009/1/UMURJ-Issue09_2012-StudentAbstractCompetition.pd

University of Michigan Undergraduate Research Journal, Issue 9, Winter 2012

Articlehttp://deepblue.lib.umich.edu/bitstream/2027.42/97010/1/UMURJ-Issue09_2012.pd

Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts

BIN1 is not expressed in human brain microglial cells. (A) Immunohistochemical staining of adjacent sections of normal human brain cortex with antibodies against BIN1 or Iba1 reveals that BIN1 immunoreactive cells that are morphologically distinct from microglia. The boxed region is shown at a higher magnification on the right. (B) Single and two-color immunostaining of the human brain using antibodies against BIN1 and CD45 reveals that perivenular CD45-positive cells of the hematopoietic lineage do not express BIN1. (TIFF 4392 kb

Safety and improved efficacy signals following gene therapy in childhood blindness caused by GUCY2D mutations

A first-in-human clinical trial of gene therapy in Leber congenital amaurosis due to mutations in the GUCY2D gene is underway, and early results are summarized. A recombinant adeno-associated virus serotype 5 (rAAV5) vector carrying the human GUCY2D gene was delivered by subretinal injection to one eye in three adult patients with severe visual loss, nystagmus, but preserved retinal structure. Safety and efficacy parameters were monitored for 9 months post-operatively. No systemic toxicity was detected; there were no serious adverse events, and ocular adverse events resolved. P1 and P2 showed statistically significant rod photoreceptor vision improvement by full-field stimulus testing in the treated eye. P1 also showed improvement in pupillary responses. Visual acuity remained stable from baseline in P1 and P2. P3, however, showed a gain of 0.3 logMAR in the treated eye, indicating greater cone-photoreceptor function. The results show safety and both rod- and cone-mediated efficacy of this therapy

nab-Paclitaxel–Based Therapy in Underserved Patient Populations: The ABOUND.PS2 Study in Patients With NSCLC and a Performance Status of 2

IntroductionThe phase II ABOUND.PS2 study (NCT02289456) assessed safety/tolerability of a first-line modified nab-paclitaxel/carboplatin regimen for patients with advanced non-small cell lung cancer (NSCLC) and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2.MethodsChemotherapy-naive patients with stage IIIB/IV NSCLC and ECOG PS 2 received four cycles of nab-paclitaxel 100 mg/m2 days 1 and 8 plus carboplatin area under the curve 5 day 1 q3w (induction). Patients without progression received nab-paclitaxel monotherapy (100 mg/m2 days 1 and 8 q3w) until progression/unacceptable toxicity. Primary endpoint: percentage of patients discontinuing induction due to treatment-emergent adverse events (TEAEs).Results11/40 treated patients (27.5%; 95% CI, 14.60–43.89) discontinued chemotherapy induction due to TEAEs; 16/40 (40.0%) continued nab-paclitaxel monotherapy. Median progression-free and overall survival were 4.4 (95% CI, 2.99–7.00) and 7.7 (95% CI, 4.93–13.17) months. Grade 3/4 TEAEs during induction included neutropenia (22.5%), anemia (17.5%), thrombocytopenia (5.0%), and peripheral neuropathy (2.5%).ConclusionThis nab-paclitaxel–based regimen was tolerable in patients with advanced NSCLC and ECOG PS 2, with efficacy comparable to historical chemotherapy data

Night Vision Restored in Days After Decades of Congenital Blindness

Signaling of vision to the brain starts with the retinal phototransduction cascade which converts visible light from the environment into chemical changes. Vision impairment results when mutations inactivate proteins of the phototransduction cascade. A severe monogenically inherited blindness, Leber congenital amaurosis (LCA), is caused by mutations in the GUCY2D gene, leading to a molecular defect in the production of cyclic GMP, the second messenger of phototransduction. We studied two patients with GUCY2D-LCA who were undergoing gene augmentation therapy. Both patients had large deficits in rod photoreceptor-based night vision before intervention. Within days of therapy, rod vision in both patients changed dramatically; improvements in visual function and functional vision in these hyper-responding patients reached more than 3 log10 units (1000-fold), nearing healthy rod vision. Quick activation of the complex molecular pathways from retinal photoreceptor to visual cortex and behavior is thus possible in patients even after being disabled and dormant for decades

Comparative Omics-Driven Genome Annotation Refinement: Application across Yersiniae

Genome sequencing continues to be a rapidly evolving technology, yet most downstream aspects of genome annotation pipelines remain relatively stable or are even being abandoned. The annotation process is now performed almost exclusively in an automated fashion to balance the large number of sequences generated. One possible way of reducing errors inherent to automated computational annotations is to apply data from omics measurements (i.e. transcriptional and proteomic) to the un-annotated genome with a proteogenomic-based approach. Here, the concept of annotation refinement has been extended to include a comparative assessment of genomes across closely related species. Transcriptomic and proteomic data derived from highly similar pathogenic Yersiniae (Y. pestis CO92, Y. pestis Pestoides F, and Y. pseudotuberculosis PB1/+) was used to demonstrate a comprehensive comparative omic-based annotation methodology. Peptide and oligo measurements experimentally validated the expression of nearly 40% of each strain's predicted proteome and revealed the identification of 28 novel and 68 incorrect (i.e., observed frameshifts, extended start sites, and translated pseudogenes) protein-coding sequences within the three current genome annotations. Gene loss is presumed to play a major role in Y. pestis acquiring its niche as a virulent pathogen, thus the discovery of many translated pseudogenes, including the insertion-ablated argD, underscores a need for functional analyses to investigate hypotheses related to divergence. Refinements included the discovery of a seemingly essential ribosomal protein, several virulence-associated factors, a transcriptional regulator, and many hypothetical proteins that were missed during annotation

Senior Recitals

Senior recital presented at the UNT College of Music Voertman Hall in partial fulfillment of the Bachelor of Music (BM) in Performance degree

Symptom-related attributional biases in schizophrenia and bipolar disorder

Impairments in social cognition are known to have severe impacts on functional outcome in schizophrenia. Attributional biases (i.e., biases towards assigning blame/credit to oneself, other people, or to the situation) are of particular interest due to their direct relevance to paranoid delusions and potential implication in cognitive-based treatments. A "defense" model of paranoid delusions proposed by Bentall, Kinderman, and Kaney (1994) suggests that paranoid individuals possess an extreme self-serving bias, with a specific tendency to blame other people as opposed to the situation (i.e., personalizing bias). In addition, an inability to integrate belief-disconfirming information is thought to underlie the fixedness of delusions. However, these biases have not been investigated simultaneously to check for additive or multiplicative effects on associations with symptoms. Moreover, previous studies have failed to take into account the heterogeneity of the symptoms of psychosis. The present research employed structural equation modelling and constrained principal component analysis in schizophrenia patients, bipolar disorder patients, and healthy individuals to examine the extent to which group differences and symptom severity could predict patterns of responding on a novel attributional bias task, designed to assess an individual's ability to integrate contextual information in conjunction with attributional reasoning. In line with the defense model of paranoia, it was predicted that schizophrenia patients with severe paranoid delusions would display enhanced self-serving and personalizing biases. However, no differences between diagnostic- or symptom-based participant groups were found. Conversely, the severity of symptoms of overactive disorganization in schizophrenia and bipolar disorder patients predicted higher situation attributions and self-blame (specifically when such attributions were unsupported by the available evidence), while higher depression in healthy participants was negatively related to situation attributions and lower self-credit. These findings suggest that non-self-serving bases may be non-specifically related to high psychopathology, while an ability to integrate socially-relevant contextual information to consider other people’s roles in events may be reduced in overactive disorganization in mental illness, and is negatively related to depression in healthy individuals. The absence of noticeable group differences in attributional biases illustrates the importance of employing a multivariate symptom-based approach when studying complex cognitive processes in psychosis.Medicine, Faculty ofGraduat

Resources to improve the efficiency and effectiveness of ThaiWheel wheelchairs.

The goal of our project was to develop a resource package to help facilitate improvements in the ThaiWheel organization. The package included information for future opportunities and a program to calculate total wheelchair costs when making or buying parts. Methods included focus groups, obtaining government and manufacturing contacts, and writing an Economic Analysis and Total Cost program. Recommendations included future donation strategies, using the program to improve cost efficiency, and to make the large initial investment on the domestically supplied brakes determined in the scenario