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2016

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Articles 31 - 60 of 71

Full-Text Articles in Medical Cell Biology

The Role Of Collagen Interacting Proteins In The Pathogenesis Of Filifactor Alocis, Ozioma Salomey Chioma Jun 2016

The Role Of Collagen Interacting Proteins In The Pathogenesis Of Filifactor Alocis, Ozioma Salomey Chioma

Loma Linda University Electronic Theses, Dissertations & Projects

Filifactor alocis is a Gram-positive, asaccharolytic; obligate anaerobe that has emerged as a potential periodontal pathogen due to its presence in high numbers in patients who have periodontal disease and least detection in healthy individuals (Kumar et al., 2003, Kumar et al., 2006, Wade, 2011). There is compelling evidence in the literature that demonstrates that F. alocis has virulence properties that may play an important role in infection-induced periodontitis (Abusleme et al., 2013, Griffen et al., 2012, Hutter et al., 2003, Khader et al., 2006, Siqueira and Rocas, 2003, Siqueira et al., 2009). However, there is a gap in our …


Priming Cardiovascular Stem Cells For Transplantation Using Short-Term Hypoxia, Ivan Hernandez Jun 2016

Priming Cardiovascular Stem Cells For Transplantation Using Short-Term Hypoxia, Ivan Hernandez

Electronic Theses, Projects, and Dissertations

Conventional medical treatments fail to address the underlying problems associated with the damage inflicted by a coronary event. Thus, the long-term prognosis of patients admitted for heart failure is disheartening, with reported survival rates of 25 percent. Recent advances in stem cell research highlight the potential benefits of autologous stem cell transplantation for stimulating repair in heart tissue. However, a majority of those suffering from cardiovascular diseases are older adults whose autologous cells no longer possess optimum functional capacity. Additional work is needed to identify the optimal cell types or conditions that will promote cardiovascular regeneration across all age groups. …


Synapse Formation In Monosynaptic Sensory–Motor Connections Is Regulated By Presynaptic Rho Gtpase Cdc42, Fumiyasu Imai, David R. Ladle, Jennifer R. Leslie, Xin Duan, Tilat A. Rizvi, Georgianne M. Ciraolo, Yi Zheng, Yutaka Yoshida May 2016

Synapse Formation In Monosynaptic Sensory–Motor Connections Is Regulated By Presynaptic Rho Gtpase Cdc42, Fumiyasu Imai, David R. Ladle, Jennifer R. Leslie, Xin Duan, Tilat A. Rizvi, Georgianne M. Ciraolo, Yi Zheng, Yutaka Yoshida

Neuroscience, Cell Biology & Physiology Faculty Publications

Spinal reflex circuit development requires the precise regulation of axon trajectories, synaptic specificity, and synapse formation. Of these three crucial steps, the molecular mechanisms underlying synapse formation between group Ia proprioceptive sensory neurons and motor neurons is the least understood. Here, we show that the Rho GTPase Cdc42 controls synapse formation in monosynaptic sensory–motor connections in presynaptic, but not postsynaptic, neurons. In mice lacking Cdc42 in presynaptic sensory neurons, proprioceptive sensory axons appropriately reach the ventral spinal cord, but significantly fewer synapses are formed with motor neurons compared with wild-type mice. Concordantly, electrophysiological analyses show diminished EPSP amplitudes in monosynaptic …


The Structure And Regulation Of Cullin 2 Based E3 Ubiquitin Ligases And Their Biological Functions., Weijia Cai, Haifeng Yang May 2016

The Structure And Regulation Of Cullin 2 Based E3 Ubiquitin Ligases And Their Biological Functions., Weijia Cai, Haifeng Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Cullin-RING E3 ubiquitin ligase complexes play a central role in targeting cellular proteins for ubiquitination-dependent protein turnover through 26S proteasome. Cullin-2 is a member of the Cullin family, and it serves as a scaffold protein for Elongin B and C, Rbx1 and various substrate recognition receptors to form E3 ubiquitin ligases.

MAIN BODY OF THE ABSTRACT: First, the composition, structure and the regulation of Cullin-2 based E3 ubiquitin ligases were introduced. Then the targets, the biological functions of complexes that use VHL, Lrr-1, Fem1b, Prame, Zyg-11, BAF250, Rack1 as substrate targeting subunits were described, and their involvement in diseases …


Multiphoton Imaging Of Labeled Breast Cancer Cells To Quantify Intra And Extracellular Receptors, Sydney C. Wiggins May 2016

Multiphoton Imaging Of Labeled Breast Cancer Cells To Quantify Intra And Extracellular Receptors, Sydney C. Wiggins

Biomedical Engineering Undergraduate Honors Theses

Every year 200,000 women in the United States are diagnosed with breast cancer. Of the cases diagnosed, 10% -15% are classified as triple negative breast cancer (TNBC) due to the absence of estrogen, progesterone, and HER-2/Neu receptors. This breast cancer sub-type is markedly more aggressive and twice as likely to develop in premenopausal women. TNBC is resistant to endocrine therapies and current targeted agents, making clinical need for the development of validated therapeutics for TNBC a pressing matter. To initiate drug development, the internalization of directly immunolabeled epidermal growth factor receptors (EGFR) in SK-BR-3 human breast adenocarcinoma cells was quantitated …


Neurocalcin ẟ Response To Calcium: Which Ef Hand Matters The Most?, Trokon Fiawoo May 2016

Neurocalcin ẟ Response To Calcium: Which Ef Hand Matters The Most?, Trokon Fiawoo

Graduate School of Biomedical Sciences Theses and Dissertations

Changes in intracellular calcium levels play a very important role in cell signaling, in turn, affecting neuronal functions such as memory, learning and cell death. A class of proteins called Neuronal Calcium Sensor (NCS) proteins serves to modulate the functioning of the neuronal cells in response to changes in calcium levels. Structurally, all NCS proteins have 4 calcium-binding EF hand motifs, although EF I does not bind to calcium in many members. All NCS proteins are myristoylated at the N-terminus. Neurocalcin delta (NCALD) is an NCS protein, and shares 95% similarity in primary amino acid sequence with another major NCS …


In Vitro Investigation Of The Effect Of Exogenous Ubiquitin On Processes Associated With Atherosclerosis, Chase W. Mussard May 2016

In Vitro Investigation Of The Effect Of Exogenous Ubiquitin On Processes Associated With Atherosclerosis, Chase W. Mussard

Undergraduate Honors Theses

Atherosclerosis, characterized by the build-up of cholesterol, immune cells and cellular debris within arterial walls, is accelerated following myocardial infarction by poorly understood mechanisms. Ubiquitin, a small, well-studied intracellular protein involved in protein turnover via the proteasome pathway, has recently been shown to exert extracellular effects on cardiac myocytes, in vitro, and in mice undergoing myocardial remodeling. This study investigates the potential role of extracellular ubiquitin in atherosclerosis by determining its effects on two critical atherosclerotic processes: the migration of vascular smooth muscles cells and the uptake of modified LDL by monocyte/macrophages in foam cell formation. In the presence …


Investigating The Regulation And Function Of The Nr4a Nuclear Receptors In Cancer, Jordan A. Beard May 2016

Investigating The Regulation And Function Of The Nr4a Nuclear Receptors In Cancer, Jordan A. Beard

Theses and Dissertations (ETD)

The nuclear receptor (NR) superfamily represents a structurally-conserved group of ligand-regulated transcription factors. These proteins have critical roles in various physiological and pathological processes, including cancer, and have been targets of drug therapy. The orphan NR subfamily 4A (NR4A), which includes the NR4A1 (Nur77), NR4A2 (Nurr1), and NR4A3 (Nor-1) genes, has been implicated in adult solid tumors and has been characterized as pro-tumorigenic mediator of cell proliferation, transformation, migration, and drug resistance. Alternatively, in leukemia, NR4A1 and NR4A3 have been described as tumor suppressors in hematologic malignancies. Members of the NR4A family are commonly overexpressed in cancer and this has …


Pten Signaling In Regulatory T Cells And Inflammatory Disease, Sharad Krishna Shrestha May 2016

Pten Signaling In Regulatory T Cells And Inflammatory Disease, Sharad Krishna Shrestha

Theses and Dissertations (ETD)

Regulatory T (Treg) cells suppress CD4+ T cell responses during homeostasis and inflammation to prevent autoimmunity and other immune disorders. Although the transcriptional and epigenetic programs impacting Treg cell function have been extensively studied, the signaling and metabolic pathways underlying Treg stability and function are not fully understood. In this study, we determined the role of the phosphatase PTEN in Treg cells. We found that specific depletion of PTEN in Treg cells results in excessive TH1 and T follicular helper cells (TFH) responses, associated with elevated germinal center (GC) B cells and spontaneous development of autoimmune and lymphoproliferative disease in …


Investigation Of Novel Functions For Dna Damage Response And Repair Proteins In Escherichia Coli And Humans, Benjamin A. Hilton May 2016

Investigation Of Novel Functions For Dna Damage Response And Repair Proteins In Escherichia Coli And Humans, Benjamin A. Hilton

Electronic Theses and Dissertations

Endogenous and exogenous agents that can damage DNA are a constant threat to genome stability in all living cells. In response, cells have evolved an array of mechanisms to repair DNA damage or to eliminate the cells damaged beyond repair. One of these mechanisms is nucleotide excision repair (NER) which is the major repair pathway responsible for removing a wide variety of bulky DNA lesions. Deficiency, or mutation, in one or several of the NER repair proteins is responsible for many diseases, including cancer. Prokaryotic NER involves only three proteins to recognize and incise a damaged site, while eukaryotic NER …


Cell-Based Therapies For Ischemic Cardiomyopathy : Investigations Of Intramyocardial Retention And Safety Of High Dose Intracoronary Delivery Of C-Kit Positive Cardiac Progenitor Cells, And Therapeutic Utility Of A Novel Population Of Cardiac Mesenchymal Stem Cells Expressing Stage-Specific Embryonic Antigen-3 (Ssea-3)., Matthew C. L. Keith May 2016

Cell-Based Therapies For Ischemic Cardiomyopathy : Investigations Of Intramyocardial Retention And Safety Of High Dose Intracoronary Delivery Of C-Kit Positive Cardiac Progenitor Cells, And Therapeutic Utility Of A Novel Population Of Cardiac Mesenchymal Stem Cells Expressing Stage-Specific Embryonic Antigen-3 (Ssea-3)., Matthew C. L. Keith

Electronic Theses and Dissertations

Over the last decade attempts at reducing morbidity and mortality of patients with chronic heart failure have been made via the development and implementation of novel cell based therapies. Substantial advances in cell based therapies with indications of efficacy have been shown along with a robust safety profile. Despite these advances, there is a substantial unmet need for novel therapies, specifically addressing repair and regeneration of the damaged or lost myocardium and its vasculature. Accordingly, cardiac cell-based therapies have gained attention. Various cell-types have been utilized, including bone marrow-derived mononuclear cells, bone marrow-derived mesenchymal stem cells, mobilized CD34+ cells, …


Acrolein Is A Critical Mediator Of Alcohol-Induced Liver And Intestinal Injury In Alcoholic Liver Disease., Wei-Yang (Jeremy) Chen May 2016

Acrolein Is A Critical Mediator Of Alcohol-Induced Liver And Intestinal Injury In Alcoholic Liver Disease., Wei-Yang (Jeremy) Chen

Electronic Theses and Dissertations

Alcohol consumption can cause alcoholic liver disease (ALD), which remains a major cause of morbidity and mortality in the United States. Chronic alcohol consumption causes a pro-oxidant environment in the liver and increases hepatic lipid peroxidation. Acrolein is the most reactive and toxic aldehyde generated through lipid peroxidation. Acrolein forms protein adducts and triggers endoplasmic reticulum (ER) stress and hepatocyte apoptosis, which are recognized etiologic factors in ALD. Several studies have established the critical role of the gut-liver axis in ALD pathogenesis, wherein alcohol-induced gut barrier dysfunction contributes to liver injury. This study investigates, in vitro and in vivo, the …


Cardiac Tissue Engineering: Using Induced Pluripotent Stem Cells To Repair Damaged Cardiac Tissue, Megan Lenz Apr 2016

Cardiac Tissue Engineering: Using Induced Pluripotent Stem Cells To Repair Damaged Cardiac Tissue, Megan Lenz

Celebrating Scholarship & Creativity Day (2011-2017)

Heart Disease is the number one cause of death in the United States and affects many individuals on a daily basis. The purpose of this research was to explore possible tissue regeneration therapies that aim to improve and recover function of damaged myocardial tissue commonly seen as a side-effect of chronic heart disease. Cardiac tissue engineering using induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) is a relatively new method that involves dedifferentiating cells from any tissue of the host into pluripotent stem cells. These cells are then guided to be differentiated into functioning myocardial cells that can be used to …


Use Of Propensity Score Matching To Identify A Strong Association Between Strategic Concentration To Mitochondria-Sr Associations Of The Mitochondrial Ca2+ Uniporter: Ca2+ Uptake Hotspots In The Cardiac Mitochondria, Sergio De La Fuente, Caitlin Vail, Elorm J. Agra, Kira Holmstrom, Junhui Sun, Jyotsna Mishra, Toren Kinkel, Elizabeth Murphy, Suresh K. Joseph, Shey-Shing Shen, György Csordás Apr 2016

Use Of Propensity Score Matching To Identify A Strong Association Between Strategic Concentration To Mitochondria-Sr Associations Of The Mitochondrial Ca2+ Uniporter: Ca2+ Uptake Hotspots In The Cardiac Mitochondria, Sergio De La Fuente, Caitlin Vail, Elorm J. Agra, Kira Holmstrom, Junhui Sun, Jyotsna Mishra, Toren Kinkel, Elizabeth Murphy, Suresh K. Joseph, Shey-Shing Shen, György Csordás

Department of Pathology, Anatomy, and Cell Biology Posters

Introduction:

  • Control of the mitochondrial ATP production by SR-derived Ca2+ signals includes local, nanodomain Ca2+ transfer from ryanodine receptors (RyR2) to the mitochondrial matrix (excitation-bioenergetics coupling).
  • Ca2+ crosses the inner mitochondrial membrane (IMM) via the mtCU, a low-affinity Ca2+-activated Ca2+ channel complex.
  • The surface area of cardiac IMM is extensively enhanced by cristae folding; however, mitoplast patch clamp studies showed mtCU current density the lowest amongst a range of tissues (Fieni 2012. Nat Commun).


Gaining Competencies During Early Medical Training: Medical Students As Teaching Assistants In Dissection-Based Anatomy Course, Martin T. Brown, Bruce Fenderson, Guiyan Zhang Apr 2016

Gaining Competencies During Early Medical Training: Medical Students As Teaching Assistants In Dissection-Based Anatomy Course, Martin T. Brown, Bruce Fenderson, Guiyan Zhang

Department of Pathology, Anatomy, and Cell Biology Posters

Introduction and Objectives

  • In 2002, ACGME identified six ACGME Core Competencies: patient care; medical knowledge; practice-based learning and improvement; interpersonal and communication skills; professionalism; and systems-based practice.
  • AAMC recommended lists of similar competencies for the curricula of medical schools. Competency based curricula have been widely implemented in medical schools.
  • Effective shifting in the graduate medical educational programs has been reported in various clinical specialties.
  • There is a lack of reported efforts and development on competency training in early preclinical years of medical education.

Objectives:

  • To explore methods for strengthening medical students’ competency training during preclinical undergraduate medical education.
  • To measure …


Micu1 Regulation Of Mitochondrial Ca(2+) Uptake Dictates Survival And Tissue Regeneration., Anil Noronha Antony, Melanie Paillard, Cynthia Moffat, Egle Juskeviciute, Jason Correnti, Brad Bolon, Emanual Rubin, Md, György Csordás, Erin L Seifert, Jan B. Hoek, György Hajnóczky Mar 2016

Micu1 Regulation Of Mitochondrial Ca(2+) Uptake Dictates Survival And Tissue Regeneration., Anil Noronha Antony, Melanie Paillard, Cynthia Moffat, Egle Juskeviciute, Jason Correnti, Brad Bolon, Emanual Rubin, Md, György Csordás, Erin L Seifert, Jan B. Hoek, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mitochondrial Ca(2+) uptake through the recently discovered Mitochondrial Calcium Uniporter (MCU) is controlled by its gatekeeper Mitochondrial Calcium Uptake 1 (MICU1). However, the physiological and pathological role of MICU1 remains unclear. Here we show that MICU1 is vital for adaptation to postnatal life and for tissue repair after injury. MICU1 knockout is perinatally lethal in mice without causing gross anatomical defects. We used liver regeneration after partial hepatectomy as a physiological stress response model. Upon MICU1 loss, early priming is unaffected, but the pro-inflammatory phase does not resolve and liver regeneration fails, with impaired cell cycle entry and extensive necrosis. …


Role Of Heme Oxygenase-1 In The Pathogenesis And Tumorigenicity Of Kaposi's Sarcoma-Associated Herpesvirus, Lu Dai, Jing Qiao, David Nguyen, Amanda P. Struckhoff, Lisa Doyle, Karlie Bonstaff, Luis Del Valle, Chris Parsons, Bryan P. Toole, Rolf Renne, Zhiqiang Qin Mar 2016

Role Of Heme Oxygenase-1 In The Pathogenesis And Tumorigenicity Of Kaposi's Sarcoma-Associated Herpesvirus, Lu Dai, Jing Qiao, David Nguyen, Amanda P. Struckhoff, Lisa Doyle, Karlie Bonstaff, Luis Del Valle, Chris Parsons, Bryan P. Toole, Rolf Renne, Zhiqiang Qin

School of Medicine Faculty Publications

Kaposi's Sarcoma-associated Herpesvirus (KSHV) is the etiologic agent of several malignancies, including Kaposi's Sarcoma (KS), which preferentially arise in immunocompromised patients such as HIV+ subpopulation and lack effective therapeutic options. Heme oxygenase-1 (HO-1) has been reported as an important regulator of endothelial cell cycle control, proliferation and angiogenesis. HO-1 has also been found to be highly expressed in KSHV-infected endothelial cells and oral AIDS-KS lesions. We previously demonstrate that the multifunctional glycoprotein CD147 is required for KSHV/LANA-induced endothelial cell invasiveness. During the identification of CD147 controlled downstream genes by microarray analysis, we found that the expression of HO-1 is significantly …


Structure-Activity Relationships Governing The Interaction Of Nanoparticles With Mammalian Cells- Predictive Models For Toxicology And Medical Appliances, Marcus A. Maher Mar 2016

Structure-Activity Relationships Governing The Interaction Of Nanoparticles With Mammalian Cells- Predictive Models For Toxicology And Medical Appliances, Marcus A. Maher

Doctoral

Nanoscience is seen as one of the key enabling technologies of the 20th century and as its range of applications increases it is important to look at how nanomaterials interact with biological environments. Some of these interactions have given rise to toxic effects and thus, the creation of the field of nanotoxicology, it has also been noted that current methods of evaluating toxicity may not be sufficient to keep up with the rapidly emerging range of nanomaterials becoming available. It is clear that alternatives are necessary. In this thesis, a phenomenological rate equation model is constructed to simulate nanoparticle uptake …


Microcystic, Elongated, And Fragmented (Melf) Pattern Invasion In Ovarian Endometrioid Carcinoma: Immunohistochemical Profile And Prognostic Implications, Allison F. Goldberg, Md, Lauren Cooper, Md, D. De Cotiis, Norman G. Rosenblum, Md, Phd, Joanna Chan, Md Feb 2016

Microcystic, Elongated, And Fragmented (Melf) Pattern Invasion In Ovarian Endometrioid Carcinoma: Immunohistochemical Profile And Prognostic Implications, Allison F. Goldberg, Md, Lauren Cooper, Md, D. De Cotiis, Norman G. Rosenblum, Md, Phd, Joanna Chan, Md

Department of Pathology, Anatomy, and Cell Biology Resident's Posters

BACKGROUND

•Microcystic, Elongated and Fragmented (MELF) is a well-recognized pattern of uterine endometrioid carcinoma (UEC) associated with lymphovascular space invasion and occult lymph node metastasis

•MELF in UEC may be seen with Lynch Syndrome

•MELF in UEC is hypothesized to be histologic evidence of an epithelial mesenchymal transition

•MELF pattern invasion in ovarian endometrioid carcinoma (OEC) was first described at USCAP 2015 •

Current study evaluates MELF in OEC for

•Prognostic implications

•Immunohistochemical (IHC) profile related to

•Lynch Syndrome

•Epithelial mesenchymal transition

DESIGN

•42 consecutive cases of OEC without concurrent UEC (1996-2014) evaluated by 2 pathologists

•MELF defined as at …


Two Separate Colorectal Granular Cell Tumors: A Case Report, Danica N. Giugliano, Md, Danielle Fortuna, Md, Scott D. Goldstein, Md, Benjamin Philllips, Md, Gerald A. Isenberg, Md Feb 2016

Two Separate Colorectal Granular Cell Tumors: A Case Report, Danica N. Giugliano, Md, Danielle Fortuna, Md, Scott D. Goldstein, Md, Benjamin Philllips, Md, Gerald A. Isenberg, Md

Department of Surgery Posters

Introduction, Case Report, Discussion, Conclusion and References.


Microrna Dysregulation And Esophageal Cancer Development Depend On The Extent Of Zinc Dietary Deficiency., Louise Fong, Cristian Taccioli, Ruiyan Jing, Karl Smalley, Hansjuerg Alder, Yubao Jiang, Paolo Fadda, John Farber, Carlo M Croce Feb 2016

Microrna Dysregulation And Esophageal Cancer Development Depend On The Extent Of Zinc Dietary Deficiency., Louise Fong, Cristian Taccioli, Ruiyan Jing, Karl Smalley, Hansjuerg Alder, Yubao Jiang, Paolo Fadda, John Farber, Carlo M Croce

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Zinc deficiency (ZD) increases the risk of esophageal squamous cell carcinoma (ESCC), and marginal ZD is prevalent in humans. In rats, marked-ZD (3 mg Zn/kg diet) induces a proliferative esophagus with a 5-microRNA signature (miR-31, -223, -21, -146b, -146a) and promotes ESCC. Here we report that moderate and mild-ZD (6 and 12 mg Zn/kg diet) also induced esophageal hyperplasia, albeit less pronounced than induced by marked-ZD, with a 2-microRNA signature (miR-31, -146a). On exposure to an environmental carcinogen, ~16% of moderate/mild-ZD rats developed ESCC, a cancer incidence significantly greater than for Zn-sufficient rats (0%) (P ≤ 0.05), but lower than …


Challenges Of Adoptive (T-)Cell Transfer Immunotherapy For Cancer, Aaron Volk Feb 2016

Challenges Of Adoptive (T-)Cell Transfer Immunotherapy For Cancer, Aaron Volk

Biology: Student Scholarship & Creative Works

Background and significance: The rebirth of the theory of immunosurveillance in 2001 rejuvenated interest in anticancer immunotherapies. In particular, T-cell-based therapies have garnered substantial interest due to the robustness and tumor antigen-specific cytotoxicity of T-cell anticancer immune responses.

Hypothesis: The efficacy of adoptive cell transfer (ACT) T-cell immunotherapy could significantly improve and gain widespread approval if future innovations in ACT-based approaches account for the pro- and antitumoral properties of non-CD8+ lineages of effector T-cells, evasion of T-cell antitumor immunity, and tumor-induced suppression of antitumor immunity.

Problem Analysis: Despite numerous reports of highly successful ACT-based clinical trials, no such therapy …


Prevalence And Spectrum Of Brca Germline Variants In Mainland Chinese Familial Breast And Ovarian Cancer Patients., Yeong C. Kim, Linli Zhao, Hanwen Zhang, Ye Huang, Jian Cui, Fengxia Xiao, Bradley Downs, San Ming Wang Feb 2016

Prevalence And Spectrum Of Brca Germline Variants In Mainland Chinese Familial Breast And Ovarian Cancer Patients., Yeong C. Kim, Linli Zhao, Hanwen Zhang, Ye Huang, Jian Cui, Fengxia Xiao, Bradley Downs, San Ming Wang

Journal Articles: Genetics, Cell Biology & Anatomy

Germline mutations in BRCA1 and BRCA2 are the most penetrating genetic predispositions for breast and ovarian cancer, and their presence is largely ethnic-specific. Comprehensive information about the prevalence and spectrum of BRCA mutations has been collected in European and North American populations. However, similar information is lacking in other populations, including the mainland Chinese population despite its large size of 1.4 billion accounting for one fifth of the world's population. Herein, we performed an extensive literature analysis to collect BRCA variants identified from mainland Chinese familial breast and ovarian cancer patients. We observed 137 distinct BRCA1 variants in 409 of …


Mitogenic Activation And Proliferation Of T Lymphocytes In Trpm7 Kinase-Dead Mutant Mice, Pavani Beesetty, Masayuki Matsushita, J. Ashot Kozak Feb 2016

Mitogenic Activation And Proliferation Of T Lymphocytes In Trpm7 Kinase-Dead Mutant Mice, Pavani Beesetty, Masayuki Matsushita, J. Ashot Kozak

Neuroscience, Cell Biology & Physiology Faculty Publications

Calcium and magnesium ions have been implicated in T lymphocyte proliferation in response to antigen recognition. Specifically, it is believed that calcium and magnesium elevations in the cytoplasm are necessary for efficient T cell proliferation. Research over the past two decades has focused on identifying the plasma membrane ion channels responsible for governing Ca2+ influx in lymphocytes and Orai-STIM, Kv1.3 and KCa3.1 channels were shown to be crucial for persistent calcium mobilization. Pharmacologic or genetic suppression of calcium influx gives rise to lymphoproliferative defects. In addition to Ca2+, several studies have demonstrated that Mg2+ influx positively regulates proliferation. TRPM7 is …


Cells Activated For Wound Repair Have The Potential To Direct Collective Invasion Of An Epithelium., Brigid M Bleaken, A Sue Menko, Janice Walker Feb 2016

Cells Activated For Wound Repair Have The Potential To Direct Collective Invasion Of An Epithelium., Brigid M Bleaken, A Sue Menko, Janice Walker

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mechanisms regulating how groups of cells are signaled to move collectively from their original site and invade surrounding matrix are poorly understood. Here we develop a clinically relevant ex vivo injury invasion model to determine whether cells involved in directing wound healing have invasive function and whether they can act as leader cells to direct movement of a wounded epithelium through a three-dimensional (3D) extracellular matrix (ECM) environment. Similar to cancer invasion, we found that the injured cells invade into the ECM as cords, involving heterotypical cell-cell interactions. Mesenchymal cells with properties of activated repair cells that typically locate to …


Cd147 And Downstream Adamtss Promote The Tumorigenicity Of Kaposi's Sarcoma-Associated Herpesvirus Infected Endothelial Cells, Lu Dai, Jimena Trillo-Tinoco, Yihan Chen, Karlie Bonstaff, Luis Del Valle, Chris Parsons, Augusto C. Ochoa, Jovanny Zabaleta, Bryan P. Toole, Zhiqiang Qin Jan 2016

Cd147 And Downstream Adamtss Promote The Tumorigenicity Of Kaposi's Sarcoma-Associated Herpesvirus Infected Endothelial Cells, Lu Dai, Jimena Trillo-Tinoco, Yihan Chen, Karlie Bonstaff, Luis Del Valle, Chris Parsons, Augusto C. Ochoa, Jovanny Zabaleta, Bryan P. Toole, Zhiqiang Qin

School of Medicine Faculty Publications

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of several human cancers, including Kaposi's sarcoma (KS), which preferentially arise in immunocompromised patients and lack effective therapeutic options. We have previously shown that KSHV or viral protein LANA up-regulates the glycoprotein CD147, thereby inducing primary endothelial cell invasiveness. In the current study, we identify the global network controlled by CD147 in KSHV-infected endothelial cells using Illumina microarray analysis. Among downstream genes, two specific metalloproteases, ADAMTS1 and 9, are strongly expressed in AIDS-KS tissues and contribute to KSHV-infected endothelial cell invasiveness through up-regulation of IL-6 and VEGF. By using a KS-like nude …


Reversible Recruitment Of A Homeostatic Reserve Pool Of Synaptic Vesicles Underlies Rapid Homeostatic Plasticity Of Quantal Content, Xueyong Wang, Martin J. Pinter, Mark M. Rich Jan 2016

Reversible Recruitment Of A Homeostatic Reserve Pool Of Synaptic Vesicles Underlies Rapid Homeostatic Plasticity Of Quantal Content, Xueyong Wang, Martin J. Pinter, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

Homeostatic regulation is essential for the maintenance of synaptic strength within the physiological range. The current study is the first to demonstrate that both induction and reversal of homeostatic upregulation of synaptic vesicle release can occur within seconds of blocking or unblocking acetylcholine receptors at the mouse neuromuscular junction. Our data suggest that the homeostatic upregulation of release is due to Ca2+-dependent increase in the size of the readily releasable pool (RRP). Blocking vesicle refilling prevented upregulation of quantal content (QC), while leaving baseline release relatively unaffected. This suggested that the upregulation of QC was due to mobilization …


In-Silico Identification Of Prognostically Inversely Correlated Mirnas And Mrnas (Pic’S) In Multiple Cancers, Chirayu Pankaj Goswami, Zi-Xuan Wang Jan 2016

In-Silico Identification Of Prognostically Inversely Correlated Mirnas And Mrnas (Pic’S) In Multiple Cancers, Chirayu Pankaj Goswami, Zi-Xuan Wang

Department of Pathology, Anatomy, and Cell Biology Posters

Despite numerous methods available to identify potential mRNA targets for miRNAs, prognostic relationship of these molecules in diseases like cancers where deregulation of gene expression is a major pathogenic factor, has not yet been emphasized. We performed in-silico identification of prognostically inversely correlated miRNA - mRNA pairs (PIC’s) in multiple cancers using expression data from The Cancer Genome Atlas. Partners in a PIC show inverse correlation of expression and opposite hazard implication. Using a three step approach, we identified a total of 1,253,443 PIC’s from 23 cancer types, several of which have previously been shown to have a predicted or …


Exome Screening To Identify Loss-Of-Function Mutations In The Rhesus Macaque For Development Of Preclinical Models Of Human Disease, Adam Cornish, Robert M. Gibbs, Robert B. Norgren Jan 2016

Exome Screening To Identify Loss-Of-Function Mutations In The Rhesus Macaque For Development Of Preclinical Models Of Human Disease, Adam Cornish, Robert M. Gibbs, Robert B. Norgren

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: Exome sequencing has been utilized to identify genetic variants associated with disease in humans. Identification of loss-of-function mutations with exome sequencing in rhesus macaques (Macaca mulatta) could lead to valuable animal models of genetic disease. Attempts have been made to identify variants in rhesus macaques by aligning exome data against the rheMac2 draft genome. However, such efforts have been impaired due to the incompleteness and annotation errors associated with rheMac2. We wished to determine whether aligning exome reads against our new, improved rhesus genome, MacaM, could be used to identify high impact, loss-of-function mutations in rhesus macaques that would …


Hexokinase Ii Localization Is Independent Of Ampk Activation In Hela Cells, Alyssa Brown Jan 2016

Hexokinase Ii Localization Is Independent Of Ampk Activation In Hela Cells, Alyssa Brown

Graduate School of Biomedical Sciences Theses and Dissertations

In order for a cancer cell to thrive, it must alter its metabolism to produce the energy needed for rapid growth. Cells accomplish this by the Warburg Effect, or switching metabolism to aerobic glycolysis, where a cell can rapidly break down sugar into ATP, lactic acid and additional byproducts. Hexokinase 2, the enzyme that catalyzes the first committed step of glycolysis, may also be upregulated in cancer cells to increase glucose breakdown. Similar proteins for metabolism are found in both S. cerevisiae and mammalian cells. S. cerevisiae regulates metabolism through glucose repression, by Snf1 (mammalian homolog: AMPK) activation, which aids …