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Medulloblastomas Overexpress The P53-Inactivating Oncogene Wip1/Ppm1d, Robert C. Castellino, Massimiliano De Bortoli, Xiongbin Lu, Sung-Hwan Moon, Thuy-Ai Nguyen, Mark A. Shepard, Pulivarthi H. Rao, Lawrence A. Donehower, John Y H Kim

Faculty, Staff and Students Publications

Medulloblastoma is the most common malignant brain tumor of childhood. Despite numerous advances, clinical challenges range from recurrent and progressive disease to long-term toxicities in survivors. The lack of more effective, less toxic therapies results from our limited understanding of medulloblastoma growth. Although TP53 is the most commonly altered gene in cancers, it is rarely mutated in medulloblastoma. Accumulating evidence, however, indicates that TP53 pathways are disrupted in medulloblastoma. Wild-type p53-induced phosphatase 1 (WIP1 or PPM1D) encodes a negative regulator of p53. WIP1 amplification (17q22-q23) and its overexpression have been reported in diverse cancer types. We examined primary medulloblastoma specimens …

Beta 1-Integrins Are Required For Hippocampal Ampa Receptor-Dependent Synaptic Transmission, Synaptic Plasticity, And Working Memory, Chi-Shing Chan, Edwin J. Weeber, Lin Zong, Elaine Fuchs, J David Sweatt, Ronald L. Davis

Faculty, Staff and Students Publications

Integrins comprise a large family of cell adhesion receptors that mediate diverse biological events through cell-cell and cell-extracellular matrix interactions. Recent studies have shown that several integrins are localized to synapses with suggested roles in synaptic plasticity and memory formation. We generated a postnatal forebrain and excitatory neuron-specific knock-out of beta1-integrin in the mouse. Electrophysiological studies demonstrated that these mutants have impaired synaptic transmission through AMPA receptors and diminished NMDA receptor-dependent long-term potentiation. Despite the impairment in hippocampal synaptic transmission, the mutants displayed normal hippocampal-dependent spatial and contextual memory but were impaired in a hippocampal-dependent, nonmatching-to-place working memory task. These …

Gene Therapy For Pediatric Cancer: State Of The Art And Future Perspectives, Ettore Biagi, Catherine Bollard, Raphael Rousseau, Malcolm Brenner

Faculty, Staff and Students Publications

While modern treatments have led to a dramatic improvement in survival for pediatric malignancy, toxicities are high and a significant proportion of patients remain resistant. Gene transfer offers the prospect of highly specific therapies for childhood cancer. "Corrective" genes may be transferred to overcome the genetic abnormalities present in the precancerous cell. Alternatively, genes can be introduced to render the malignant cell sensitive to therapeutic drugs. The tumor can also be attacked by decreasing its blood supply with genes that inhibit vascular growth. Another possible approach is to modify normal tissues with genes that make them more resistant to conventional …

Atomic Models For The Polypeptide Backbones Of Myohemerythrin And Hemerythrin, W A Hendrickson, K B Ward

Faculty, Staff and Students Publications

Background: The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly after its identification in December 2019 to cause a global pandemic. The respiratory tract is the primary site of infection, and there is a large range in the severity of respiratory illnesses caused by the virus. Defining molecular and cellular factors for protection from severe disease and death has been a goal to better understand and to predict and mitigate the effects of SARS-CoV-2 and future coronaviruses.

Objective: Despite well-known susceptibilities to respiratory viral infections, respiratory allergy and allergic asthma have not been identified as risk factors …

The Parenchymal Cells Of The Rat Pineal Gland, E Tapp, M Blumfield

Faculty, Staff and Students Publications

Background: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare hematologic disorder with improved survival due to advancements in treatment. However, long-term cardiovascular morbidity and mortality remain significant. Established cardiovascular risk calculators, such as the 2008 Framingham Heart Study (FHS) global cardiovascular disease (CVD) and the American College of Cardiology/American Heart Association (ACC/AHA) atherosclerotic CVD (ASCVD) risk estimators, may not adequately account for the elevated and unique cardiovascular risks in iTTP survivors.

Objectives: To evaluate the discrimination and calibration of the ACC/AHA ASCVD and FHS global CVD models in predicting major adverse cardiovascular events (MACEs) among iTTP survivors.

Methods: This retrospective …