Medical Cell Biology Commons^™

Hormone-Induced Calcium Oscillations Depend On Cross-Coupling With Inositol 1,4,5-Trisphosphate Oscillations., Lawrence D Gaspers, Paula J Bartlett, Antonio Politi, Paul Burnett, Walson Metzger, Jane Johnston, Suresh K Joseph, Thomas Höfer, Andrew P Thomas

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Receptor-mediated oscillations in cytosolic Ca(2+) concentration ([Ca(2+)]i) could originate either directly from an autonomous Ca(2+) feedback oscillator at the inositol 1,4,5-trisphosphate (IP3) receptor or as a secondary consequence of IP3 oscillations driven by Ca(2+) feedback on IP3 metabolism. It is challenging to discriminate these alternatives, because IP3 fluctuations could drive Ca(2+) oscillations or could just be a secondary response to the [Ca(2+)]i spikes. To investigate this problem, we constructed a recombinant IP3 buffer using type-I IP3 receptor ligand-binding domain fused to GFP (GFP-LBD), which buffers IP3 in the physiological range. This IP3 buffer slows hormone-induced [IP3] dynamics without changing steady-state …

Seeing Is Believing: Optical Computed Tomography (Oct) And Histologic Analysis To Define Pathophysiology Of “Very”, Very Late Stent Thrombosis Occurring More Than 7 Years After Drug Eluting Stent Implantation, Antony G. Kaliyadan, Md, Alec Vishnevsky, Md, Henry Siu, Md, David Fishman, Md, John Farber, Md, Nicholas Ruggiero Ii, Md, Michael P. Savage, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Case Presentation

• 58-year-old male with prior non-ST elevation MI with PCI performed using a sirolimus eluting stent placed in a large OM1 branch 86 months prior presented with five hours chest pain similar to prior MI >7 years earlier.
• Additional history of hypertension, hyperlipidemia, non-compliance with antiplatelet therapy and active tobacco abuse at time of presentation.
• Patient reported self-discontinuation of medications (aspirin (time unknown), statin, beta blocker) and resumed smoking.
• Clopidogrel was discontinued by his primary physician 97 days prior to presentation
• Initial electrocardiogram revealed a lateral ST elevation MI and the patient was taken to the cardiac catheterization lab …

Loss Of Miro1-Directed Mitochondrial Movement Results In A Novel Murine Model For Neuron Disease., Tammy T Nguyen, Sang S Oh, David Weaver, Agnieszka Lewandowska, Dane Maxfield, Max-Hinderk Schuler, Nathan K Smith, Jane Macfarlane, Gerald Saunders, Cheryl A Palmer, Valentina Debattisti, Takumi Koshiba, Stefan Pulst, Eva L Feldman, György Hajnóczky, Janet M Shaw

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Defective mitochondrial distribution in neurons is proposed to cause ATP depletion and calcium-buffering deficiencies that compromise cell function. However, it is unclear whether aberrant mitochondrial motility and distribution alone are sufficient to cause neurological disease. Calcium-binding mitochondrial Rho (Miro) GTPases attach mitochondria to motor proteins for anterograde and retrograde transport in neurons. Using two new KO mouse models, we demonstrate that Miro1 is essential for development of cranial motor nuclei required for respiratory control and maintenance of upper motor neurons required for ambulation. Neuron-specific loss of Miro1 causes depletion of mitochondria from corticospinal tract axons and progressive neurological deficits mirroring …

Inputs Drive Cell Phenotype Variability., James Park, Anthony Brureau, Kate Kernan, Alexandria Starks, Sonali Gulati, Babatunde Ogunnaike, James S. Schwaber, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

What is the significance of the extensive variability observed in individual members of a single-cell phenotype? This question is particularly relevant to the highly differentiated organization of the brain. In this study, for the first time, we analyze the in vivo variability within a neuronal phenotype in terms of input type. We developed a large-scale gene-expression data set from several hundred single brainstem neurons selected on the basis of their specific synaptic input types. The results show a surprising organizational structure in which neuronal variability aligned with input type along a continuum of sub-phenotypes and corresponding gene regulatory modules. Correlations …

Chronic Arsenic Exposure And Angiogenesis In Human Bronchial Epithelial Cells Via The Ros/Mir-199a-5p/Hif-1Α/Cox-2 Pathway., Jun He, Min Wang, Yue Jiang, Qiudan Chen, Shaohua Xu, Qing Xu, Bing-Hua Jiang, Ling-Zhi Liu

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Environmental and occupational exposure to arsenic is a major public health concern. Although it has been identified as a human carcinogen, the molecular mechanism underlying the arsenic-induced carcinogenesis is not well understood.Objectives: We aimed to determine the role and mechanisms of miRNAs in arsenic-induced tumor angiogenesis and tumor growth.Methods: We utilized an in vitro model in which human lung epithelial BEAS-2B cells were transformed through long-term exposure to arsenic. A human xenograft tumor model was established to assess tumor angiogenesis and tumor growth in vivo. Tube formation assay and chorioallantoic membranes assay were used to assess tumor angiogenesis.Results: We …