Medical Cell Biology Commons^™

Delayed Thrombus Resolution And Fibroproliferative Vascular Wound Healing From Deficiency Of Type Iii Collagen: A Paradoxical Mechanism For Tissue Fragility, Amy J. Reid

UT GSBS Dissertations and Theses (Open Access)

Vascular Ehlers-Danlos syndrome is a heritable disease of connective tissue caused by mutations in COL3A1, conferring a tissue deficiency of type III collagen. Cutaneous wounds heal poorly in these patients, and they are susceptible to spontaneous and catastrophic rupture of expansible hollow organs like the gut, uterus, and medium-sized to large arteries, which leads to premature death. Although the predisposition for organ rupture is often attributed to inherent tissue fragility, investigation of arteries from a haploinsufficient Col3a1 mouse model (Col3a1^+/-) demonstrates that mutant arteries withstand even supraphysiologic pressures comparably to wild-type vessels. We hypothesize that injury that elicits occlusive thrombi ...

Characterizing Stomatin-Like Protein 2 And Its Role In Neuron Survival, Lisa A. Foris

University of Western Ontario - Electronic Thesis and Dissertation Repository

Stomatin-like Protein 2 (SLP-2) has been identified as a stress-inducible transcript and has been shown to interact with and stabilize mitochondrial proteins. Since mitochondria are critical for neuronal function, we hypothesized that SLP-2 regulates neuron survival in response to stressful stimuli. A conditional SLP-2 knockout mouse (deletion) and the SN56 cell line (upregulation) were employed to study the role of SLP-2 in mitochondrial dynamics and neuron survival. SLP-2 deficient primary cortical neurons displayed significantly decreased levels of various mitochondrial respiratory chain proteins, indicating SLP-2 contributes to maintenance of mitochondrial membrane integrity. SLP-2 was up-regulated in response to oxidative stress and ...

Human Enteric Glial Cells Alleviate Damaged Adult Sensory Neurons In Rats, Dhara Shah, Cai Jiang, Kiran Reddy, Caixin Su, Shucui Jiang

The Meducator

Spinal cord injury affects millions across the globe. Little is known regarding the cellular mechanism of injury and, unfortunately, there are few viable treatment options. One potential option is the transplantation of peripheral nerves into the site of injury. The complicating factor is that the peripheral nervous system is not readily accessible, and thus the procedure introduces the risk of disrupting the function of other areas. However, this risk is minimized if the nerves are extracted from the enteric system, which is embedded in the lining of the gastrointestinal tract. This system bears similarities to the central nervous system, has ...

Tumour Heterogeneity And Treatment: One Step Forward Or Two Steps Back?, Branavan Manoranjan, Mohsin Ali

The Meducator

No abstract provided.

Induction Of Neurotrophic And Differentiation Genes In Neural Stem Cells By Valproic Acid, Walaa Saeed Almutawaa

Open Access Dissertations and Theses

Valproic acid (2-propylpentanoicacid) has long been in use as an anticonvulsant and mood-stabilizer. Recently, VPA has been shown to inhibit the activity of histone deacetylases (HDACs), resulting in chromatin remodelling and changes in gene expression. Although the molecular mechanism for VPA action in the central nervous is not well understood, many signalling pathways have been suggested as targets for this HDAC inhibitor. For instance, VPA was found to induce differentiation in adult hippocampal neural progenitor cells via the β-catenin-Ras-ERK pathway. Also, VPA up regulated Bcl-2, a neurotrophic/neuroprotective protein, with association of extracellular signal-regulated kinase (ERK-1) and phosphatidylinositol 3- kinase ...

The Pluripotency Proposition: A Biological And Ethical Case For The Utilization Of Hipscs In Place Of Hescs, Drew Dickson

Senior Honors Papers

Human embryonic stem cell (hESC) research has spurred ethical controversy ever since it became feasible in 1998. The reason for this is due to the fact that hESC research requires the destruction of a human embryo, thereby causing the cessation of life for that developing human. Despite this unavoidable consequence, many advocates of hESC research hold to the belief that the embryo is not actually a human person, and therefore deem the destruction of the embryo as justifiable. Many advocates of hESC research also have pointed to the unprecedented medical potential of hESCs to argue in favor of their case ...

Flash4 Dark Reference Images, George Mcnamara

George McNamara

Hamamatsu FLASH4.0 dark reference images, acquired with 10 second exposure times, no light to camera. Camera offset (set by Hamamatsu( is ~100 (the average intensity of the first image is always ~1 intensity level higher - an odd feature, but trivial in practice for a 16-bit camera).

George McNamara, Ph.D.

Single Cells Analyst at L.J.N. Cooper Lab

University of Texas M.D. Anderson Cancer Center

Multifactorial Modulation Of The Blood-Brain Barrier: Relationship To Stroke, Bei Zhang

Theses and Dissertations--Nutritional Sciences

The blood-brain barrier (BBB) is a dynamic interface, mainly consisting of highly specialized brain microvascular endothelial cells (BMECs) that segregate the central nervous system (CNS) from the peripheral circulation. Impairment of the BBB, due to disruption of tight junction (TJ) proteins and inflammatory responses, may initiate and/or contribute to the progress of CNS disorders, including stroke. Stroke is the second leading cause of death worldwide. It has been shown that aging and environmental pollutants can induce brain endothelium dysfunction, and are considered as risk factors for stroke.

Deficiency of telomerase is highly linked with aging-associated vascular diseases. Evidence indicates ...

Video Codec Performance (Excel Spreadsheet), George Mcnamara

George McNamara

Video codec performance (Excel spreadsheet). Movie was made in 2005-2006 when I worked at City of Hope National Medical Center. VTLF refers to Video Timelapse Light Facility. Videos were outputted from MetaMorph as AVI files. Personally, I always recommend uncompressed video files fro scientific uses. I also encourage posting the original scientific data format (ex. .lsm, .zvi, .lif, .stk).

The Role Of Dax-1 In Regulating Pluripotency In Mouse Embryonic Stem Cells, Anthony Torres

Master Theses

The orphan receptor Dax-1 is highly expressed in pluripotent embryonic stem (ES) cells and shows a correlative reduction in expression as these cells differentiate. While it is known that Dax-1 is expressed in pluripotent mouse ES cells, the precise function of Dax-1 in these cells is not as well understood. Recent studies employing RNA interference (RNAi) to specifically reduce the expression of the Dax-1 gene in mouse ES cells found that upon the knock down of Dax-1, ES cells differentiated. These findings indicate that Dax-1 functions in a novel role in the maintenance of a relatively undifferentiated state in ES ...

Pubspectra Tattletales, George Mcnamara

George McNamara

Tattletales for Multiplex Fluorescent Reporters in Single Cells for Metabolomics

George McNamara

Analytical Imaging Core Facility, University of Miami, Miller School of Medicine, Miami, FL

As of April 2013: L.J.N. Cooper & D.A. Lee Cellular Immunotherapy Lab, University of Texas M.D. Anderson Cancer Center, Houston, TX

Email: gmcnamara@med.miami.edu, geomcnamara@earthlink.net

Tattletales is my concept for spatial multiplexing many fluorescent protein (FP) biosensors in the same live cell. For example, there are excellent FP biosensors to Ca++ ions, pH, glucose, ribose, glutamine, glutamate, ATP, redox, ROS, pyruvate, cAMP, cGMP, IP3, PI(3,4,5)P3, cell cycle indicators (Fucci2), PKA, PKC, photsphatases, caspase(s) [1, 2]. However, these are typically used one biosensor per experiment, due in part to flooding the cell with soluble biosensor. That is, conventionally, either a metabolite (glucose) reporter or a signal transduction (Ca++) reporter can be imaged. By flooding the cell with the reporter, signal to noise ratio is compromized by autofluorescence.

Tattletales takes advantage of spatial multiplexing to both increase the number of different reporters, and improve signal to noise ratio by localizing each biosensor to a small volume. I started with the observation by Robinett et al [3] who localized 512 GFP-nls-LacI to a 256 LacO array as a 200 nm diameter diffraction limited spot (nuclear background due to overexpression). Many thousands of DNA binding proteins, of known sequence specifities, exist (LacI, TetR, GalR, etc for cell line studies; ZF-FPs, TALE-FPs to STRs, telomere repeat binding factors-FPs, etc for primary cells) and can be fused (as cDNAs) to different fluorescent proteins and FP biosensors.

Many biosensors are available as affinity series [1, 4], now enabling extended dynamic range. I realized that spatial multiplexing of many DNA binding protein-reporters by localizing to different spots in the cell nucleus and distinguished by combinatorial addressing, where N address colors ...

Libraries At The University Of Massachusetts Amherst: Seeking An International Perspective, Maxine G. Schmidt

Maxine G Schmidt

Presentation delivered to librarians in China, Japan and South Korea as part of my sabbatical research on the use of libraries by Asian students in their home countries.

Histology Slide, John Farber

The Medicine Forum

A 45 year old Black female without significant past medical history was admitted with insidious cough, dyspnea, nausea, vomiting, and progressive weight loss. She suddenly went into respiratory distress and succumbed to death. Autopsy subsequently showed widespread granulomatous disease. This slide of one of the lung lesions shows a noncaseating granulocyte with a fibrotic center surrounded by palisading histiocytes, consistent with a diagnosis of nodular sarcoma.

Cord Compression By Extramedullary Hematopoiesis In Polycythemia Vera, Lisa Reale, Steve Zrada, Jose Martinez

The Medicine Forum

A 73-year-old male with polycythemia vera and a history of prostate cancer presents to an outside hospital complaining of back pain of two months duration. He denied fevers, chills, night sweats, weight loss, lower extremity weakness and decreased sensation. Other than chronic constipation and urinary hesitancy, his review of systems was unremarkable. A spinal x-ray revealed a T12 vertebral fracture and the patient was transferred to Thomas Jefferson University Hospital for further management.

Halloween 2012 Jack O'Lanterns Trick Or Treat, George Mcnamara

George McNamara

Halloween 2012 makes trick or treating more visual and interactive than in past years.

the download is a ZIP file containing three files.

Print out the (unnumbered) image on as large and nice printer paper as possible - I used glossy 44" wide here in Miami (University of Miami, MillerSchool of Medicine, Calder Library, Biomedical Communications dept - I also made another print on "fabric", also 44" wide to take with me to an HHMI Janelia Farm conference on 'turning images into knowledge' that ends on Oct 31 - might stay up for a second conference, "GFP..." that start Nov 4).

The other ...

Investigation Into The Unique Roles Of Mmp-2 And Mmp-9 In Tgfβ-Induced Epithelial-Mesenchymal Transition In Lens Epithelial Cells, Anna Korol

Open Access Dissertations and Theses

Epithelial-mesenchymal transition (EMT) is a pathological process leading to the formation of anterior subcapsular cataract (ASC). Mediated by transforming growth factor beta (TGFβ), EMT involves the transformation of the monolayer of lens epithelial cells (LECs) into spindle-shaped myofibroblasts, which manifest as plaques directly beneath the lens capsule. TGFβ-induced EMT leading to ASC has been associated with the upregulation of two specific matrix metalloproteinases (MMPs), MMP-2 and MMP-9. Having identified MMP-2 and MMP-9 as participants in the formation of cataracts, the specific roles of either of these MMPs have yet to be determined.

The current study utilized MMP-2 and -9 knockout ...

Mini-Review: Decorin, A Guardian From The Matrix, Thomas Neill, Liliana Schaefer, Renato V. Iozzo

Department of Pathology, Anatomy and Cell Biology Faculty Papers

Decorin, an archetypal member of the small leucine-rich proteoglycan gene family, has a broad binding repertoire that encompasses matrix structural components, such as collagens, and growth factors, particularly those that belong to the transforming growth factor-β ligand superfamily. Within the tumor microenvironment, stromal decorin has an inherent proclivity to directly bind and down-regulate several receptor tyrosine kinases, which are often overexpressed in cancer cells. The decorin interactome commands a powerful antitumorigenic signal by potently repressing and attenuating tumor cell proliferation, survival, migration, and angiogenesis. This collection of interacting molecules also regulates key downstream signaling processes indirectly via the sequestration of ...

Mcnamara 20120831fri-20120904tue Cosmic Ray Particles By Ccd Imaging, George Mcnamara

George McNamara

McNamara 20120831Fri-20120904Tue Cosmic Ray Particles by CCD imaging.zip contains image files in support of a Microscopy Today article - please see

http://www.microscopy-today.com/

Cosmic Ray Particles Images With Orca-Ii Erg, George Mcnamara

George McNamara

Cosmic ray particles image series acquired using a Hamamatsu ORCA-II ERG scientific grade CCD camera, cooled to -60 C. Each image is a consecutive 600 second (10 minute) exposure time with no light to the camera.

While processing the data, I discoverd that the background changed around planes 25 and 227 (see Excel file and jpeg screenshots), so I also processed only planes 025-227 (203 planes total, 2030 minutes, 33.83 hours). the CCD industry "rule of thumb" for a "typical" CCD sensor (i.e. 1/3" CCD) is that one cosmic ray particle strikes a sensor approximately every 30 ...

Regulation Of Lipogenesis By Cyclin-Dependent Kinase 8-Mediated Control Of Srebp-1., Xiaoping Zhao, Daorong Feng, Qun Wang, Arian Abdulla, Xiao-Jun Xie, Jie Zhou, Yan Sun, Ellen S Yang, Lu-Ping Liu, Bhavapriya Vaitheesvaran, Lauren Bridges, Irwin J Kurland, Randy Strich, Jian-Quan Ni, Chenguang Wang, Johan Ericsson, Jeffrey E Pessin, Jun-Yuan Ji, Fajun Yang

Department of Cancer Biology Faculty Papers

Altered lipid metabolism underlies several major human diseases, including obesity and type 2 diabetes. However, lipid metabolism pathophysiology remains poorly understood at the molecular level. Insulin is the primary stimulator of hepatic lipogenesis through activation of the SREBP-1c transcription factor. Here we identified cyclin-dependent kinase 8 (CDK8) and its regulatory partner cyclin C (CycC) as negative regulators of the lipogenic pathway in Drosophila, mammalian hepatocytes, and mouse liver. The inhibitory effect of CDK8 and CycC on de novo lipogenesis was mediated through CDK8 phosphorylation of nuclear SREBP-1c at a conserved threonine residue. Phosphorylation by CDK8 enhanced SREBP-1c ubiquitination and protein ...