Medical Cell Biology Commons^™

Integrated Live Imaging And Molecular Profiling Of Embryoid Bodies Reveals A Synchronized Progression Of Early Differentiation., Jonathan Boxman, Naor Sagy, Sirisha Achanta, Rajanikanth Vadigepalli, Iftach Nachman

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Embryonic stem cells can spontaneously differentiate into cell types of all germ layers within embryoid bodies (EBs) in a highly variable manner. Whether there exists an intrinsic differentiation program common to all EBs is unknown. Here, we present a novel combination of high-throughput live two-photon imaging and gene expression profiling to study early differentiation dynamics spontaneously occurring within developing EBs. Onset timing of Brachyury-GFP was highly variable across EBs, while the spatial patterns as well as the dynamics of mesendodermal progression following onset were remarkably similar. We therefore defined a 'developmental clock' using the Brachyury-GFP signal onset timing. Mapping snapshot …

Activated Clotting Time (Act): Comparison Of The Hemochron Signature Elite And The Abbott I-Stat, Lilah Evans, Susanne Gallo, Joseph J. Leo, Barbara Goldsmith, Phd, Facb

Department of Pathology, Anatomy, and Cell Biology Posters

BACKGROUND

ACT is commonly used for heparin anticoagulation monitoring during procedures including cardiopulmonary bypass surgery, coronary angioplasty, and interventional radiology. To prevent thrombosis, moderate to high levels of heparin anticoagulation are required. The Hemochron Signature Elite (HSE, Accriva Diagnostics, formerly ITC, San Diego, CA) was implemented at TJUH as a replacement for the older model Hemochron Response (Accriva/ITC Model HRS.110, San Diego, CA). Operating room (OR) perfusionists reported irreproducible high results using HSE that could not be explained clinically. In consideration of use of i-STAT analyzers (Abbott Point of Care, Princeton, NJ) as an alternative to HSE, we performed a …

Performance Of Creatinine And Chloride On The Epoc Analyzer, Lilah Evans, Susanne Gallo, Stacey K. Mardekian, Barbara Goldsmith, Phd, Facb

Department of Pathology, Anatomy, and Cell Biology Posters

BACKGROUND

The epoc Blood Analysis System (Alere, Orlando, FL) performs blood gases, electrolytes, and metabolites using a Blood Gas Electrolyte and Metabolite (BGEM) Test Card panel on 92 uL of whole blood. The BGEM test card uses potentiometric sensors to measure sodium, potassium, ionized calcium, pH, pCO2; amperometric sensors to measure pO2, glucose, and lactate; and a conductometric sensor to measure hematocrit. Results are available in 3-10 minutes, depending upon the time between calibration and patient testing. TJUH implemented the epoc in its ICUs in 2012 to provide Point of Care (POC) results. Alere recently added creatinine and chloride sensors …

The Role Of E. Coli Transcript-Cleavage Factors Gre In Transcriptional Regulation Under Hyperosmotic Stress, Kseniya Obraztsova

Graduate School of Biomedical Sciences Theses and Dissertations

Escherichia coli adapts to changes in the osmotic environment through the process of osmotic response which entails synthesis of specific enzymes and transporters to accumulate essential osmoprotectants. This process is highly regulated at the level of transcription. Upon cell exposure to high salt, RNA polymerase (RNAP} rapidly dissociates from genomic DNA, while the nucleoid becomes hyper condensed. During the subsequent osmoadaptation phase RNAP reassociates with the DNA and resumes transcription. The mechanisms of transcription initiation, promoter escape and its regulation during osmoadaptation are poorly understood. Here we demonstrate that a highly conserved bacterial regulator, transcript cleavage factor GreA, is essential …

The Genetic Hierarchy Of The Heterochronic Pathway In C. Elegans, Jennifer Tsialikas

Graduate School of Biomedical Sciences Theses and Dissertations

The correct timing of developmental events is fundamental to the growth of every animal. The pathways that control developmental timing and cell-fate succession are complex and robust in a way that underscores this importance. In this work, I have shown how an early developmental regulator, LIN-14, acts to integrate the earliest aspects of development with the events that take place afterward. I have uncovered how microRNAs from two different families fit into the cascade of proteins and micro RNA regulation that defines the developmental timing pathway. Finally, my work has helped to uncover the dual-acting nature of two proteins in …

The Role Of Neurovascular Compromise, Autoimmune Antibodies And Neuronal Calcium Sensor Proteins During The Onset And Progression Of Alzheimer's Disease - Linking The Retina With The Brain, Hao Wu

Graduate School of Biomedical Sciences Theses and Dissertations

Alzheimer's disease (AD), the main cause of dementia, is a progressive and irreversible neurodegenerative disease. The pathological hallmarks of the disease include bloodbrain barrier (BBB) breach, neurofibrillary tang les and amyloid plaques. Also, emerging evidence has raised the possibility that instead of a secondary consequence, the neuroinflammation contributes to the development and early progression of AD. However, the mechanism underlying the blood-neural barrier (BNB), chronic inflammation and neuronal degenerative diseases (NDDs) remain to be elucidated.

To explore the role of the chronic inflammation in NDDs and delineate the early steps of these diseases, in vivo drug-induced and transgenic mouse models …

Reduced Motor Neuron Excitability Is An Important Contributor To Weakness In A Rat Model Of Sepsis, Paul Nardelli, Jacob A. Vincent, Randall K. Powers, Timothy C. Cope, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

The mechanisms by which sepsis triggers intensive care unit acquired weakness (ICUAW) remain unclear. We previously identified difficulty with motor unit recruitment in patients as a novel contributor to ICUAW. To study the mechanism underlying poor recruitment of motor units we used the rat cecal ligation and puncture model of sepsis. We identified striking dysfunction of alpha motor neurons during repetitive firing. Firing was more erratic, and often intermittent. Our data raised the possibility that reduced excitability of motor neurons was a significant contributor to weakness induced by sepsis. In this study we quantified the contribution of reduced motor neuron …

Regulation Of Breast Cancer Initiation And Progression By 14-3-3zeta, Chia-Chi Chang

Dissertations and Theses (Open Access)

14-3-3ζ is a ubiquitously expressed family member of proteins that have been implicated to have oncogenic potential through its interactions and involvement in cancer initiation and progression. 14-3-3ζ belongs to the highly conserved 14-3-3ζ protein family and modulates numerous pathways in cancer. Overexpression of 14-3-3ζ is an early event, occurs in more than 40% of human breast cancer cases, and is associated with disease recurrence and poor prognosis. Metabolic reprogramming is a hallmark of cancer. Cancer cells elevate aerobic glycolysis to produce metabolic intermediates and reducing equivalents, thereby facilitating cellular adaptation to the adverse environment and sustaining fast proliferation. Interestingly, …

Development Of Rational Combination Therapy With Parp Inhibitors And Kinase Inhibitors In Tnbc, Wen-Hsuan Yu

Dissertations and Theses (Open Access)

Poly (ADP-ribose) polymerase inhibitors (PARPi) emerge as potential targeting drugs for BRCA-deficient cancers including triple negative breast cancer (TNBC). However, it has been reported that a subgroup of patients even with BRCA mutation fails to respond to PARPi in multiple clinical trials. In this study, we identified c-Met, a tyrosine kinase, phosphorylates PARP1 at Y907 and that the phosphorylation increases PARP1 activity, thereby rendering cancer cells resistant to PARPi. The combination of c-Met inhibitors (METi) and PARPi has a synergistic effect for c-Met overexpressed TNBC in vitro and in vivo. In addition to c-Met, through functional analysis, we found …

The Roles Of Nuclear Receptor Nr4a1 In Cancer Cell Proliferation And Skeletal Muscle Differentiation, Alexa Farmer

Theses and Dissertations (ETD)

Nuclear receptors (NRs) constitute a major class of drug targets in the treatment of various cancer types. NRs respond to cellular signals and become activated upon ligand binding to transcriptionally modulate expression of target genes. NR4A1 (Nur77) is a member of the NR4A family of nuclear receptors and displays an oncogenic profile in many cancer models. It is often upregulated in adult solid malignancies and is known to promote cell proliferation and survival. Knockdown studies of NR4A1 in cancer cell lines results in decreased cell growth and angiogenesis and increased apoptosis, suggesting NR4A1 is an oncogenic protein. Due to the …

Exome-Based Variant Detection In Core Promoters., Yeong C. Kim, Jian Cui, Jiangtao Luo, Fengxia Xiao, Bradley Downs, San Ming Wang

Journal Articles: Genetics, Cell Biology & Anatomy

Core promoter controls the initiation of transcription. Core promoter sequence change can disrupt transcriptional regulation, lead to impairment of gene expression and ultimately diseases. Therefore, comprehensive characterization of core promoters is essential to understand normal and abnormal gene expression in biomedical studies. Here we report the development of EVDC (Exome-based Variant Detection in Core promoters) method for genome-scale analysis of core-promoter sequence variation. This method is based on the fact that exome sequences contain the sequences not only from coding exons but also from non-coding region including core promoters generated by random fragmentation in exome sequencing process. Using exome data …

Cytojournal Quiz Cases: Publishing Open-Access, Pubmed-Searchable Cytopathology Cases With Educational Messages, Katherine G. Akers, Vinod B. Shidham

Library Scholarly Publications

No abstract provided.

Microrna-Target Interactions In Embryonic Stem Cells, Shuang Wu

Graduate School of Biomedical Sciences Theses and Dissertations

Animal embryogenesis is a highly orchestrated process involving many geneexpression programs that determine specific fates of individual cells during development. Gene expression can be regulated at different stages such as at transcription initiation or mRNA stability, and microRNA-mediated gene regulation is a crucial pathway on the regulation of mRNA stability. microRNAs, or miRNAs, are small, conserved non-coding RNAs that negatively regulate gene expression post-transcriptionally. The mouse miR-290-295 cluster and its human homolog miR-371-373 are stem cell-specific miRNA clusters, and their expression can only be observed in early embryos, primordial germ cells, germ cell compartments of adult testis and embryonic stem …

Combining Real-Time Fmri Neurofeedback Training Of The Dlpfc With N-Back Practice Results In Neuroplastic Effects Confined To The Neurofeedback Target Region, Matthew Sherwood, Michael P. Weisend, Jessica H. Kane, Jason G. Parker

Neuroscience, Cell Biology & Physiology Faculty Publications

In traditional fMRI, individuals respond to exogenous stimuli and are naïve to the effects of the stimuli on their neural activity patterns. Changes arising in the fMRI signal are analyzed post-hoc to elucidate the spatial and temporal activation of brain regions associated with the tasks performed. The advent of real-time fMRI has enabled a new method to systematically alter brain activity across space and time using neurofeedback training (NFT), providing a new tool to study internally-driven processes such as neuroplasticity. In this work, we combined n-back practice with fMRI-NFT of the left dorsolateral prefrontal cortex (DLPFC) to better understand the …

Glial Cell Involvement In Early Alzheimer's Disease, Rachel Y. De La Torre

PSU McNair Scholars Online Journal

Glial cells, the resident immune cells of the brain, are important for brain health as they represent a critical function both in brain injury as well as in brain development and maintenance. Following brain injury, glia quickly respond by cleaning up neuronal and synaptic debris. In addition to their role as the cleaning cell of the brain, recent research has shown that during development, glia also shape and fine-tune neural connections by eliminating weak synapses fated for removal. However, whether glial cells also continue to remodel synaptic architecture in the adult brain is unclear. Moreover, synaptic pruning and loss are …

Theaflavin-3, 3'-Digallate Induces Apoptosis And G2 Cell Cycle Arrest Through The Akt/Mdm2/P53 Pathway In Cisplatin-Resistant Ovarian Cancer A2780/Cp70 Cells, Youying Tu, Eunhye Kim, Ying Gao, Gary O. Rankin, Bo Li, Yi Charlie Chen

Pharmacology, Physiology and Toxicology

Ovarian cancer is the most lethal gynecological cancer among women worldwide. Adverse side effects and acquired resistance to conventional platinum based chemotherapy are major impediments in ovarian cancer treatment, and drive the development of more selective anticancer drugs that target cancer-specific defects. In this study, theaflavin-3, 3'-digallate (TF3), the major theaflavin monomer in black tea, exhibited a potent growth inhibitory effect on the cisplatinresistant ovarian cancer A2780/CP70 cells (IC50, 23.81 μM), and was less cytotoxic to a normal ovarian IOSE‑364 cells (IC50, 59.58 μM) than to the cancer cells. Flow cytometry analysis indicated that TF3 induced preferential apoptosis and G2 …

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. …

Proteomic Profiling Of Serum Derived Exosomes From Prostate Cancer Patients, David Turay

Loma Linda University Electronic Theses, Dissertations & Projects

Touted among the major achievements in the diagnosis and management of Prostate cancer (PCa) in the past few decades has been, the dramatic decline of men with advanced/metastatic PCa at diagnosis coupled with a significant improvement ( >90%) in the five and ten year survival rates of the disease. Non-palpable PCa (potentially clinically treatable disease) now accounts for 70-80% of all newly diagnosed cases of PCa. Preceding these changes by about a decade was the introduction of Prostatic Specific Antigen (PSA) into clinical practice; first as biomarker for monitoring response to therapy and subsequently as a complementary screening tool. It …

Mechanism Of Chimeric Vaccine Mediated Immune Suppression Of Human Dendritic Cells, Jacques Christian Mbongue

Loma Linda University Electronic Theses, Dissertations & Projects

Type 1 diabetes mellitus is a chronic inflammatory disease in which insulin producing β-cells of the pancreatic islets are killed by autoreactive cells of the immune system in response to a loss of tolerance. Dendritic cells (DC) interact predominantly with naïve T cells to regulate the delicate balance between immunity and tolerance required to maintain immunological homeostasis. In this dissertation, immature human dendritic cells (iDC) were inoculated with a chimeric fusion protein vaccine containing the pancreatic β-cell auto-antigen proinsulin linked to a mucosal adjuvant the cholera toxin B subunit (CTB-INS). Proteomic analysis of vaccine inoculated DCs revealed strong up-regulation of …

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 …