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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Physiological Function Of Fus: An Rna Binding Protein In Motor Neuron Disease, Liuqing Yang Jan 2015

Physiological Function Of Fus: An Rna Binding Protein In Motor Neuron Disease, Liuqing Yang

Theses and Dissertations--Molecular and Cellular Biochemistry

FUS is an RNA binding protein implicated in the motor neuron disease— amyotrophic lateral sclerosis (ALS, also called Lou Gehrig’s disease). ALS is a fatal neurodegenerative disease characterized by progressive motor neuron death. Mutations in the FUS gene cause about 4% of familial ALS (FUS ALS). Mutated FUS protein mislocalizes from the motor neuron nucleus to the cytoplasm and forms inclusions in the cytoplasm. It is unclear how FUS mislocalization induces motor neuron dysfunction and degeneration. This dissertation research was designed to investigate the physiological functions of FUS in the nucleus, with a purpose to shed light on the pathogenesis …


Adp-Ribosylation Factor 6 (Arf6) Regulates Integrin Αiibβ3 Trafficking, Platelet Spreading, And Clot Retraction, Yunjie Huang Jan 2015

Adp-Ribosylation Factor 6 (Arf6) Regulates Integrin Αiibβ3 Trafficking, Platelet Spreading, And Clot Retraction, Yunjie Huang

Theses and Dissertations--Molecular and Cellular Biochemistry

Endocytic trafficking of platelet surface receptors plays a role in the accumulation of granule cargo (i.e. fibrinogen and VEGF) and thus could contribute to hemostasis, angiogenesis, or inflammation. However, the mechanisms of platelet endocytosis are poorly understood. The small GTP-binding protein, ADP-ribosylation factor 6 (Arf6), regulates integrin trafficking in nucleated cells; therefore, we posited that Arf6 functions similarly in platelets. To address this, we generated platelet-specific, Arf6 knockout mice. Arf6-/- platelets had a storage defect for fibrinogen but not other cargo, implying Arf6’s role in integrin αIIbβ3 trafficking. Additionally, platelets from Arf6-/- mice injected with biotinylated-fibrinogen, showed …


Beryllium Nitrate Supports Fibroblast Migration As An Essential Component Of Skin And Limb Regeneration In Axolotls, Adam Boyd Cook Jan 2015

Beryllium Nitrate Supports Fibroblast Migration As An Essential Component Of Skin And Limb Regeneration In Axolotls, Adam Boyd Cook

Theses and Dissertations--Biology

Tissue regeneration in salamanders is a robust process that is not easily interrupted or altered. Therefore, inhibiting regeneration provides a means to interrogate the underlying cellular and molecular mechanisms regulating this complex event. Here we show that application of a relatively low concentration of beryllium nitrate solution (100mM) causes a delay in skin regeneration and severely alters normal limb regeneration. We provide evidence showing a beryllium-induced reduction in dermal fibroblast migration in vivo and in vitro. We link this phenomenon to delayed regeneration of the skin and abnormal blastema formation resulting in limb patterning defects during regeneration. Though our …