Medical Sciences Commons^™

Pas Signaling Mechanisms In Aer And Aer2, Darysbel Garcia

Loma Linda University Electronic Theses, Dissertations & Projects

PAS domains are widespread signal sensors that share a conserved three-dimensional αβ fold that consists of a central β-sheet flanked by several α- helices. The aerotaxis receptor Aer from Escherichia coli and the Aer2 chemoreceptor from Pseudomonas aeruginosa both contain PAS domains. Aer senses oxygen (O2) indirectly via an FAD cofactor bound to its PAS domain, while Aer2 directly binds O2 to its PAS b-type heme cofactor. The Aer and Aer2 PAS domains both interact with a signal transduction domain known as a HAMP domain. The PAS-HAMP arrangement differs between Aer and Aer2, with Aer- PAS residing adjacent to its …

Targeting Ledgf/P75 To Sensitize Chemoresistant Prostate Cancer Cells To Taxanes, Leslimar Rios-Colón

Loma Linda University Electronic Theses, Dissertations & Projects

Prostate cancer (PCa) is the second most diagnosed cancer in males. This disease disproportionately affects African American men, with a higher incidence and mortality compared to other ethnic/racial groups. An aging male population and the complexity of addressing the health disparities associated with this disease puts PCa into the spotlight due to its serious public health implications and the imminent fiscal challenge over the next decades. Chronic prostate inflammation resulting in activation of stress and prosurvival pathways contribute to disease progression and the development of chemoresistance. Lens epithelium-derived growth factor p75 (LEDGF/p75) is a stressresponse protein that promotes cellular survival …

A Novel Population Of Cardiovascular Progenitors Persist In Neonates As Mesendodermal Cells, Julia Kim

Loma Linda University Electronic Theses, Dissertations & Projects

The rise in mortality due to cardiovascular disease has increased the need to develop an efficient regenerative therapeutic for heart failure. Numerous cell-based therapies have been investigated for myocardial regeneration; however, an optimal progenitor has yet to be discovered. Identifying a resident cell population with enhanced ability to differentiate into multiple lineages would greatly contribute to the field of stem cell-based regenerative therapy. Evidence suggests that endogenous cardiovascular progenitor cells (CPCs) that have been isolated from the heart itself express ISL1, KDR, and MESP1, and are capable of differentiating into all major cardiac lineages. The earlier developmental stage at which …

Prenatal Undernutrition, Metyrapone, And The Cerebrovasculature, Lara Durrant

Loma Linda University Electronic Theses, Dissertations & Projects

The link between intrauterine environmental conditions and adult cardiovascular system is well established. Independent of lifestyle factors such as poor diet and exercise habits, individuals who have been exposed to stressful conditions in utero show an increased risk of health problems such as hypertension, stroke, and type II diabetes. In support of the Fetal Origin of Adult Disease hypothesis, many labs have reported permanent anatomical and physiological changes associated with fetal stress and nutrient deficiency, with a focus on organ systems such as the kidney and heart. One key idea proposed by many of these studies is the glucocorticoid hypothesis, …

Incremental Validity Of The Pid-5 In Relation To The Five Factor Model And Traditional Polythetic Personality Criteria Of The Dsm-5, J Christopher Fowler, Michelle A Patriquin, Alok Madan, Jon G Allen, B Christopher Frueh, John M Oldham

Staff and Researcher Publications

Background: This study assessed the incremental validity of the Personality Inventory for DSM-5 (PID-5) beyond the impact of demographic, burden of illness, five-factor model of personality, and DSM-5 personality disorder criteria with respect to associations with admission psychiatric symptoms and functional disability.

Methods: Psychiatric inpatients (N = 927) were administered the Big Five Inventory, PID-5, and personality disorder criteria counts. Prior treatment utilization, as well as baseline depression, anxiety, emotion regulation, and functional disability were administered within two days of the personality measures. Hierarchical regression models were used to explore the association of personality functioning with symptom functioning, emotion regulation …

Source Localization Of Brain States Associated With Canonical Neuroimaging Postures, Michael Lifshitz, Robert T. Thibault, Raquel R. Roth, Amir Raz

Psychology Faculty Articles and Research

Cognitive neuroscientists rarely consider the influence that body position exerts on brain activity; yet, postural variation holds important implications for the acquisition and interpretation of neuroimaging data. Whereas participants in most behavioral and EEG experiments sit upright, many prominent brain imaging techniques (e.g., fMRI) require participants to lie supine. Here we demonstrate that physical comportment profoundly alters baseline brain activity as measured by magnetoencephalography (MEG)—an imaging modality that permits multipostural acquisition. We collected resting-state MEG data from 12 healthy participants in three postures (lying supine, reclining at 45°, and sitting upright). Source-modeling analysis revealed a broadly distributed influence of posture …

A Novel Micro Cold Atmospheric Plasma Device For Glioblastoma Both In Vitro And In Vivo., Zhitong Chen, Hayk Simonyan, Xiaoqian Cheng, Eda Gjika, Li Lin, Jerome Canady, Jonathan H Sherman, Colin Young, Michael Keidar

Pharmacology and Physiology Faculty Publications

: Cold atmospheric plasma (CAP) treatment is a rapidly expanding and emerging technology for cancer treatment. Direct CAP jet irradiation is limited to the skin and it can also be invoked as a supplement therapy during surgery as it only causes cell death in the upper three to five cell layers. However, the current cannulas from which the plasma emanates are too large for intracranial applications. To enhance efficiency and expand the applicability of the CAP method for brain tumors and reduce the gas flow rate and size of the plasma jet, a novel micro-sized CAP device (µCAP) was developed …

Seroprevalence Of Antibodies Against Kaposi's Sarcoma-Associated Herpesvirus Among Hiv-Negative People In China, Tiejun Zhang, Zhenqiu Liu, Jun Wang, Veenu Minhas, Charles Wood, Gary M. Clifford, Na He, Silvia Franceschi

Nebraska Center for Virology: Faculty Publications

Background: Little information on the prevalence of Kaposi’s sarcoma associated herpesvirus (KSHV) among HIV-negative individuals is available from Asia.

Methods: In the present study, we report findings from a new survey of KSHV in 983 HIV-negative male migrants from Shanghai and their combination with previous similar surveys of 600 female migrants, 600 female sex-workers (FSW), 1336 sexually transmitted infection (STI) clinic male patients, 439 intravenous drug-users (IVDU), and 226 men having sex with men (MSM) from China. KSHV-specific antibodies against latent and lytic antigens were assessed using Sf9 and BC3 monoclonal immunofluorescence assay. Age-adjusted prevalence ratios (PR) and 95% confidence …

Hypothesis Of K+-Recycling Defect Is Not A Primary Deafness Mechanism For Cx26 (Gjb2) Deficiency, Hong-Bo Zhao

Otolaryngology--Head & Neck Surgery Faculty Publications

K⁺-recycling defect is a long-standing hypothesis for deafness mechanism of Connexin26 (Cx26, GJB2) mutations, which cause the most common hereditary deafness and are responsible for >50% of nonsyndromic hearing loss. The hypothesis states that Cx26 deficiency may disrupt inner ear gap junctions and compromise sinking and recycling of expelled K⁺ ions after hair cell excitation, causing accumulation of K⁺-ions in the extracellular space around hair cells producing K⁺-toxicity, which eventually induces hair cell degeneration and hearing loss. However, this hypothesis has never been directly evidenced, even though it has been widely referred …

The 11s Proteasomal Activator Regγ Impacts Polyglutamine-Expanded Androgen Receptor Aggregation And Motor Neuron Viability Through Distinct Mechanisms., Jill M. Yersak, Heather L. Montie, Erica S. Chevalier-Larsen, Yuhong Liu, Lan Huang, Martin Rechsteiner, Diane E. Merry

Department of Biochemistry and Molecular Biology Faculty Papers

Spinal and bulbar muscular atrophy (SBMA) is caused by expression of a polyglutamine (polyQ)-expanded androgen receptor (AR). The inefficient nuclear proteasomal degradation of the mutant AR results in the formation of nuclear inclusions containing amino-terminal fragments of the mutant AR. PA28γ (also referred to as REGγ) is a nuclear 11S-proteasomal activator with limited proteasome activation capabilities compared to its cytoplasmic 11S (PA28α, PA28β) counterparts. To clarify the role of REGγ in polyQ-expanded AR metabolism, we carried out genetic and biochemical studies in cell models of SBMA. Overexpression of REGγ in a PC12 cell model of SBMA increased polyQ-expanded AR aggregation …

Analysis Of The Local And Systemic Cytokine Response Profiles In Patients With Community-Acquired Pneumonia. Relationship With Disease Severity And Outcomes., Rafael Fernandez-Botran, Timothy Lee Wiemken, Robert R. Kelley, Paula Peyrani, Jose Bordon, Rodrigo Cavallazzi, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

The goals of this study were to investigate the relationship of systemic and local cytokine responses with time to clinical stability (TCS) in patients with community-acquired pneumonia (CAP) and to develop a model to integrate multiple cytokine data into “cytokine response profiles” based on local vs. systemic and pro- vs. anti-inflammatory cytokine patterns in order to better understand their relationships with measures of CAP severity and outcomes. Forty hospitalized patients enrolled through the Community Acquired Pneumonia Inflammatory Study Group (CAPISG) were analyzed. Based on the ranked distribution of the levels of eight different pro-inflammatory cytokines and chemokines (IL-1b, IL-6, IL-8, …

Tumor Necrosis Factor Inhibitors In Psoriatic Arthritis., Santhi Mantravadi, Alexis Ogdie, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

INTRODUCTION: Psoriatic arthritis (PsA) is a chronic inflammatory disease that can result in significant disability. With the emergence of tumor necrosis factor inhibitors (TNFi), therapeutic outcomes in PsA have improved substantially. The clinical efficacy and the inhibition of radiographic progression demonstrated by TNFi have transformed the management of PsA. However, there is still an unmet need for a subset of patients who do not respond adequately to TNFi. Areas covered: This review provides an overview of the pharmacokinetics of TNFi, the efficacy of TNFi in PsA, and the role of immunogenicity of TNFi in the treatment of PsA. In addition, …

Capacitive Memory Alters Alternans And Spontaneous Activity In A Minimal Cardiomyocyte Model, Tien Comlekoglu, Seth H. Weinberg

Biology and Medicine Through Mathematics Conference

No abstract provided.

Mindfulness And Law Enforcement: An Effective Approach To Implementing Mindfulness For First Responders, Gina White

Mindfulness Studies Theses

An increasing number of studies show that people employed as first responders in high trauma service jobs tend to experience a high level of stress, at work and after hours. Studies suggest that constant exposure to job related stress leads to both physical and mental dysregulation. This study looks at the effects of implementing mindfulness tools and techniques to those working in law enforcement. Other works on this topic report mindfulness as a successful tool to increase wellbeing to a broad spectrum of populations. The methodology used in this study was designed specifically for first responders. The data findings were …

High Performance Computation Of Cardiac Models In Real-Time Using Webgl, Abouzar Kaboudian, Flavio H. Fenton

Biology and Medicine Through Mathematics Conference

No abstract provided.

Mitochondrial Dna Heteroplasmy In Cardiac Tissue From Individuals With And Without Coronary Artery Disease, Erik Hefti, Javier G. Blanco

Harrisburg University Faculty Works

The cellular environment associated with coronary artery disease (CAD) can lead to mitochondrial DNA (mtDNA) damage. Mitochondrial variants in some copies of mtDNA (heteroplasmy) and mtDNA content are potential genetic biomarkers for CAD-associated disease states. Massively parallel sequencing and qRT-PCR techniques were used to measure heteroplasmic variants and mtDNA content in heart samples from donors with (n = 8) and without (n = 7) documented CAD. Both groups showed increased numbers of heteroplasmic mtDNA variants in the control region (CR) (p < .0010, ANOVA). The donors with CAD displayed a 41.07% increase in heteroplasmic mtDNA variant number in the CR (p = .043), an 87.50% increase in the number of heteroplasmic mtDNA deletions (p = …

The Acquisition And Analysis Of Electroencephalogram Data For The Classification Of Benign Partial Epilepsy Of Childhood With Centrotemporal Spikes, Jessica A. Scarborough

Master's Theses

In this thesis, I will expand upon each step in the process of acquiring and analyzing electroencephalogram (EEG) for the classification of benign childhood epilepsy with centrotemporal spikes. Despite huge advancements in the field of health informatics—natural language processing, machine learning, predictive modeling—there are significant barriers to the access of clinical data. These barriers include information blocking, privacy policy concerns, and a lack of stakeholder support. We will see that these roadblocks are all responsible for stunting biomedical research in some way, including my own experiences in acquiring the data for the second chapter of this thesis.

This second chapter …

Uncertainty Of 1-D Fluid Models In Patients With Pulmonary Hypertension, Mitchel J. Colebank

Biology and Medicine Through Mathematics Conference

No abstract provided.

Ethical Concerns For Assisted Reproductive Technologies, Olga Najera

Dialogue & Nexus

The development of assisted reproductive technologies has provided new options for infertile couples in their pursuit of parenthood. As a result of the successful implementation of in vitro fertilization (IVF), gestational surrogacy is now an alternative. Other technology, such as genetic enhancement, could potentially become available for human beings soon; however, numerous ethical concerns have been raised by the fact that it requires germline engineering. The concerns brought about by these new reproductive technologies will be addressed in light of the teachings of the Roman Catholic Church and of the following ethical theories: Kantian, evolutionary, utilitarian, and virtue ethics.

Easi-Crispr: A Robust Method For One-Step Generation Of Mice Carrying Conditional And Insertion Alleles Using Long Ssdna Donors And Crispr Ribonucleoproteins., Rolen M Quadros, Hiromi Miura, Donald W Harms, Hisako Akatsuka, Takehito Sato, Tomomi Aida, Ronald Redder, Guy P Richardson, Yutaka Inagaki, Daisuke Sakai, Shannon M Buckley, Parthasarathy Seshacharyulu, Surinder K Batra, Mark A Behlke, Sarah A Zeiner, Ashley M Jacobi, Yayoi Izu, Wallace B Thoreson, Lisa D Urness, Suzanne L Mansour, Masato Ohtsuka, Channabasavaiah B Gurumurthy

Journal Articles: Munroe-Meyer Institute

BACKGROUND: Conditional knockout mice and transgenic mice expressing recombinases, reporters, and inducible transcriptional activators are key for many genetic studies and comprise over 90% of mouse models created. Conditional knockout mice are generated using labor-intensive methods of homologous recombination in embryonic stem cells and are available for only ~25% of all mouse genes. Transgenic mice generated by random genomic insertion approaches pose problems of unreliable expression, and thus there is a need for targeted-insertion models. Although CRISPR-based strategies were reported to create conditional and targeted-insertion alleles via one-step delivery of targeting components directly to zygotes, these strategies are quite inefficient. …

Whole Genome Analysis Of A Schistosomiasis-Transmitting Freshwater Snail., Coen M Adema, Ladeana W Hillier, Catherine S Jones, Eric S Loker, Matty Knight, Patrick Minx, +Several Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Biomphalaria snails are instrumental in transmission of the human blood fluke Schistosoma mansoni. With the World Health Organization's goal to eliminate schistosomiasis as a global health problem by 2025, there is now renewed emphasis on snail control. Here, we characterize the genome of Biomphalaria glabrata, a lophotrochozoan protostome, and provide timely and important information on snail biology. We describe aspects of phero-perception, stress responses, immune function and regulation of gene expression that support the persistence of B. glabrata in the field and may define this species as a suitable snail host for S. mansoni. We identify …

Evaluation Of An Unfractioned Heparin Pharmacy Dosing Protocol For The Treatment Of Venous Thromboembolism In Nonobese, Obese, And Severely Obese Patients, Chad A. Knoderer, Lindsey M. Hosch, Emily Y. Breedlove, Lauren E. Scono

Scholarship and Professional Work – COPHS

Background: Despite large interpatient variability in dose response, heparin is utilized for treatment of venous thromboembolism (VTE). Current data on the optimal heparin dosing in obese patients are conflicting. Objective: The objective was to evaluate the time and dose required to achieve a therapeutic activated partial thromboplastin time (aPTT) in nonobese, obese, and severely obese patients using a pharmacist-directed heparin dosing protocol. Methods: This was a retrospective cohort study in a single-center community hospital inpatient setting. Adult patients receiving heparin for VTE treatment from July 1, 2013, to July 31, 2015, were evaluated. Patients were categorized into 3 groups: nonobese …

Identification Of Octopaminergic Neurons That Modulate Sleep Suppression By Male Sex Drive., Daniel R. Machado, Dinis Afonso, Alexandra R. Kenny, Arzu Öztürk-Çolak, Emilia H. Moscato, Benjamin Mainwaring, Matthew Kayser, Kyunghee Koh

Department of Neuroscience Faculty Papers

Molecular and circuit mechanisms for balancing competing drives are not well understood. While circadian and homeostatic mechanisms generally ensure sufficient sleep at night, other pressing needs can overcome sleep drive. Here, we demonstrate that the balance between sleep and sex drives determines whether male flies sleep or court, and identify a subset of octopaminergic neurons (MS1) that regulate sleep specifically in males. When MS1 neurons are activated, isolated males sleep less, and when MS1 neurons are silenced, the normal male sleep suppression in female presence is attenuated and mating behavior is impaired. MS1 neurons do not express the sexually dimorphic …

Week Of May 15, 2017, New York Medical College

InTouch

• Department of Family and Community Medicine Hosts Fifth Annual Research Day
• Warmer Weather and Campus Greenery Gets NYMC Moving

Tumor Necrosis Factor Α Inhibition For Alzheimer's Disease, Rudy Chang, Kei-Lwun Yee, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Tumor necrosis factor α (TNF-α) plays a central role in the pathophysiology of Alzheimer’s disease (AD). Food and Drug Administration–approved biologic TNF-α inhibitors are thus a potential treatment for AD, but they do not cross the blood-brain barrier. In this short review, we discuss the involvement of TNF-α in AD, challenges associated with the development of existing biologic TNF-α inhibitors for AD, and potential therapeutic strategies for targeting TNF-α for AD therapy.

Temperature Induces Significant Changes In Both Glycolytic Reserve And Mitochondrial Spare Respiratory Capacity In Colorectal Cancer Cell Lines, Mihail I. Mitov, Jennifer W. Harris, Michael Alstott, Yekaterina Y. Zaytseva, B. Mark Evers, D. Allan Butterfield

Markey Cancer Center Faculty Publications

Thermotherapy, as a method of treating cancer, has recently attracted considerable attention from basic and clinical investigators. A number of studies and clinical trials have shown that thermotherapy can be successfully used as a therapeutic approach for various cancers. However, the effects of temperature on cancer bioenergetics have not been studied in detail with a real time, in a microplate, label-free detection approach.

This study investigate how changes in temperature affect the bioenergetics characteristics (mitochondrial function and glycolysis) of three colorectal cancer (CRC) cell lines utilizing the Seahorse XF96 technology. Experiments were performed at 32°C, 37°C and 42°C using assay …

Injury-Induced Microvesicle Particle Release In Human Skin Explant Tissue, Katherine E. Fahy, Langni Liu, Christine M. Rapp, Eric J. Romer, Christina E. Borchers, Richard Simman, Ji C. Bihl, Jeffrey B. Travers

Pharmacology and Toxicology Faculty Publications

Microvesicle particles (MVP) are 100-1000 nm vesicles that bud from the cell membrane and transmit intercellular signals locally and systemically via their bioactive cargo (e.g. cytokines).

Injury-Induced Microvesicle Particle Release In Human Skin Explant Tissue, Katherine E. Fahy, Langni Liu, Christina E. Borchers, Richard Simman, Ji C. Bihl, Jeffrey B. Travers

Pharmacology and Toxicology Faculty Publications

Microvesicle particles (MVP) are 100-1000 nm vesicles that bud from the cell membrane and transmit intercellular signals locally and systemically via their bioactive cargo (e.g. cytokines). We have previously shown that thermal burn injury or UVB radiation result in the formation Platelet Activating Factor (PAF), and UVB or a PAF agonist (CPAF) can promote MVP formation in keratinocytes. Thermal burn and UVB radiation can result in systemic effects, even though their injury is localized to the skin. We therefore propose that PAF-producing injuries, UVB irradiation or thermal burn injury, result in the formation of MVPs that can potentially transport cytokines …

Efficacy Of Electromyography And The Dead Bug Exercise, Taylor M. Scavo, Rachel C. Cooklin, Erika N. Faria, Madeline L. Johnson, Eric Sternlicht

Student Scholar Symposium Abstracts and Posters

The Dead Bug exercise is performed in physical therapy clinics to restore lumbar spine stability and core strength in patients with lower back pain (LBP). The aim of this study was to evaluate the efficacy of using electromyography (EMG) feedback to enhance proper mechanics during the Dead Bug exercise. Sixteen healthy, college age students volunteered as subjects for the study. Subjects performed the Dead Bug (Fig. 1a.) with and without visual EMG cues and were given instructions on how to execute the exercise. Data was recorded using a BTS FREEEMG Analyzer and signal processed and data analyzed using the BTS …

Structure Activity Relationship Studies Of Novel Diarylpentanoid Analogs Targeting The Androgen Receptor In Prostate Cancer Cells, Haili Coffin, Marco Bisoffi

Student Scholar Symposium Abstracts and Posters

The development of prostate cancer (PCa) relies strongly on the activation of the androgen receptor (AR) signaling pathway by its natural ligand dihydrotestosterone. Furthermore, PCa progression to metastatic disease represents oncogene addiction to AR activity. Androgen ablation therapy is thus a mainstay therapy against this disease, but the development of ligand-independent AR activation and persisting AR expression eventually leads to castration resistant PCa (CRPC). Therefore, down-regulation of AR expression in PCa cells may be an effective therapeutic modality. The diarylpentanoid ca27 has previously been shown to down-regulate AR expression by an unknown mechanism of action. The present work represents a …