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We Are… Bridging Medicine And Science, Vol. 1, Issue 3, Fall 2013, Marshall University Biomedical Sciences

We Are... Bridging Medicine Science

No abstract provided.

Synthesis And Antiproliferative Activities Of Quebecol And Its Analogs, Kasiviswanadharaju Pericherla, Amir Nasrolahi Shirazi, V. Kameshwara Rao, Rakesh Tiwari, Nicholas Dasilva, Kellen Mccaffrey, Yousef A. Beni, Antonio González- Sarrías, Navindra P. Seeram, Keykavous Parang, Anil Kumar

Pharmacy Faculty Articles and Research

Simple and efficient synthesis of quebecol and a number of its analogs was accomplished in five steps. The synthesized compounds were evaluated for antiproliferative activities against human cervix adenocarcinoma (HeLa), human ovarian carcinoma (SK-OV-3), human colon carcinoma (HT-29), and human breast adenocarcinoma (MCF-7) cancer cell lines. Among all the compounds, 7c, 7d, 7f, and 8f exhibited antiproliferative activities against four tested cell lines with inhibition over 80% at 75 mu M after 72 h, whereas, compound 7b and 7g were more selective towards MCF-7 cell line. The IC50 values for compounds 7c, 7d, and 7f were 85.1 mu M, 78.7 …

Tossing The Coin For Half Life, William L. Romine

Biological Sciences Faculty Publications

No abstract provided.

Small Molecule Antagonists Of Melanopsin-Mediated Phototransduction, Kenneth A. Jones, Megumi Hatori, Ludovic S. Mure, Jayne R. Bramley, Roman Artymyshyn, Sang-Phyo Hong, Mohammad Marzabadi, Huailing Zhong, Jeffrey Sprouse, Quansheng Zhu, Andrew T. E. Hartwick, Patricia J. Sollars, Gary E. Pickard, Satchidananda Panda

School of Veterinary and Biomedical Sciences: Faculty Publications

Melanopsin, expressed in a subset of retinal ganglion cells, mediates behavioral adaptation to ambient light and other non-image forming photic responses. This has raised the possibility that pharmacological manipulation of melanopsin can modulate several CNS responses including photophobia, sleep, circadian rhythms and neuroendocrine function. Here we describe the identification of a potent synthetic melanopsin antagonist with in vivo activity. Novel sulfonamide compounds inhibiting melanopsin (opsinamides) compete with retinal binding to melanopsin and inhibit its function without affecting rod/cone mediated responses. In vivo administration of opsinamides to mice specifically and reversibly modified melanopsin-dependent light responses including the pupillary light reflex and …

Primary Blast Traumatic Brain Injury In The Rat: Relating Diffusion Tensor Imaging And Behavior, Matthew D. Budde, Alok Shah, Michael Mccrea, William E. Cullinan, Frank A. Pintar, Brian D. Stemper

Biomedical Sciences Faculty Research and Publications

The incidence of traumatic brain injury (TBI) among military personnel is at its highest point in U.S. history. Experimental animal models of blast have provided a wealth of insight into blast injury. The mechanisms of neurotrauma caused by blast, however, are still under debate. Specifically, it is unclear whether the blast shockwave in the absence of head motion is sufficient to induce brain trauma. In this study, the consequences of blast injury were investigated in a rat model of primary blast TBI. Animals were exposed to blast shockwaves with peak reflected overpressures of either 100 or 450 kPa (39 and …

Mapping The Knowledge Economy Of Medicinal Plants In Northern Madagascar: Information And Resource Flow In Traditional Health Practices, Chanelle Adams

Independent Study Project (ISP) Collection

In the wake of pharmaceutical success with alkaloid compounds found in the Madagascar periwinkle (Catharanthus roseus), there has been increased attention towards identifying medicinal properties in the country’s rich flora. Both native and foreign companies seek profitable use of wild plant species found within Madagascar’s unique biodiversity. Many conservation organizations believe that the world’s forests in biological “hot spots” contain cures unknown to modern science and therefore, their preservation essential.

While the protection of these natural resources is important to Western medicine, it is even more vital for local people who depend on the forest as their primary …

Prostate Cancer Stem Cell-Targeted Efficacy Of A New-Generation Taxoid, Sbt-1214 And Novel Polyenolic Zinc-Binding Curcuminoid, Cmc2.24, Galina I. Botchkina, Edison S. Zuniga, Rebecca H. Rowehl, Rosa Park, Rahuldev Bhalla, Agnieszka B. Bialkowska, Francis Johnson, Lorne M. Golbu, Yu Zhang, Iwao Ojima, Kenneth R. Shroyer

Department of Biomedical Engineering Faculty Publications

Background

Prostate cancer is the second leading cause of cancer death among men. Multiple evidence suggests that a population of tumor-initiating, or cancer stem cells (CSCs) is responsible for cancer development and exceptional drug resistance, representing a highly important therapeutic target. The present study evaluated CSC-specific alterations induced by new-generation taxoid SBT-1214 and a novel polyenolic zinc-binding curcuminoid, CMC2.24, in prostate CSCs.

Principal Findings

The CD133high/CD44high phenotype was isolated from spontaneously immortalized patient-derived PPT2 cells and highly metastatic PC3MM2 cells. Weekly treatment of the NOD/SCID mice bearing PPT2- and PC3MM3-induced tumors with the SBT-1214 led to dramatic suppression of tumor …

Scavenger Receptor Class B Type I Regulates Cellular Cholesterol Metabolism And Cell Signaling Associated With Breast Cancer Development., Christiane Danilo, Jorge L Gutierrez-Pajares, Maria Antonietta Mainieri, Isabelle Mercier, Michael P. Lisanti, Philippe G. Frank

Department of Stem Cell Biology and Regenerative Medicine Faculty Papers & Presentations

INTRODUCTION: Previous studies have identified cholesterol as an important regulator of breast cancer development. High-density lipoprotein (HDL) and its cellular receptor, scavenger receptor class B type I (SR-BI) have both been implicated in the regulation of cellular cholesterol homeostasis, but their functions in cancer remain to be established.

METHODS: In the present study, we have examined the role of HDL and SR-BI in the regulation of cellular signaling pathways in breast cancer cell lines and in the development of tumor in a mouse xenograft model.

RESULTS: Our data show that HDL is capable of stimulating migration and can activate signal …

Cholinergic Enhancement Of Brain Activation In Mild Cognitive Impairment During Episodic Memory Encoding, Shannon L. Risacher, Yang Wang, Heather A. Wishart, Laura A. Rabin, Laura A. Flashman, Brenna C. Mcdonald, John D. West, Robert B. Santulli, Andrew J. Saykin

Publications and Research

Objective: To determine the physiological impact of treatment with donepezil (Aricept) on neural circuitry supporting episodic memory encoding in patients with amnestic mild cognitive impairment (MCI) using functional magnetic resonance imaging (fMRI).

Methods: Eighteen patients with MCI and 20 age-matched healthy controls (HC) were scanned twice while performing an event-related verbal episodic encoding task. MCI participants were scanned before treatment and after approximately 3 months on donepezil; HCwere untreated but rescanned at the same interval.Voxel-level analyses assessed treatment effects on activation profiles in MCI patients relative to retest changes in non-treated HC. Changes in task-related connectivity in medial temporal circuitry …

Transient And Selective Suppression Of Neural Activity With Infrared Light, Michael W. Jenkins, Hui Lu, Jeffrey M. Mcmanus, Hillel J. Chiel

Faculty Scholarship

Analysis and control of neural circuitry requires the ability to selectively activate or inhibit neurons. Previous work showed that infrared laser light selectively excited neural activity in endogenous unmyelinated and myelinated axons. However, inhibition of neuronal firing with infrared light was only observed in limited cases, is not well understood and was not precisely controlled. Using an experimentally tractable unmyelinated preparation for detailed investigation and a myelinated preparation for validation, we report that it is possible to selectively and transiently inhibit electrically- initiated axonal activation, as well as to both block or enhance the propagation of action potentials of specific …

The Role Of Nitric Oxide Dysregulation In Tumor Maintenance, Christopher Rabender

Theses and Dissertations

The inflammatory nature of the tumor microenvironment provides a cytokine and chemokine rich proliferative environment. Much of the responsibility of this environment is due to the production of Reactive Oxygen Species (ROS). These studies examined the proliferative rich tumor environment from a new perspective of Nitric Oxide Synthase (NOS) dysregulation. NOS’s have the ability to become uncoupled and generate superoxide in lieu of nitric oxide (NO). A requirement of NOS for the production of NO is the cofactor tetrahydrobiopterin (BH4) and when it is missing NOS becomes uncoupled and turns into a peroxynitrite synthase. Here I demonstrate that NOS is …

How Studies Of Human Sex Ratios At Birth May Lead To The Understanding Of Several Forms Of Pathology, William H. James

Human Biology Open Access Pre-Prints

This paper deals with the problem of the causes of the variation of sex ratio (proportion male) at birth. This problem is common to a number of areas in biology and medicine e.g. obstetrics, neurology/psychiatry, parasitology, virology, oncology and teratology. It is established that there are significantly biased, but unexplained, sex ratios in each of these fields. Yet workers in them (with the possible exception of virology) have regarded the problem as a minor loose end, irrelevant to the field’s major problems. However, as far as I know, no-one has previously noted that unexplained biased sex ratios occur, and thus …

Aspirin And Low-Molecular Weight Heparin Combination Therapy Effectively Prevents Recurrent Miscarriage In Hyperhomocysteinemic Women., Pratip Chakraborty, Sayani Banerjee, Piyali Saha, Shyam Sundar Nandi, Sunita Sharma, Sourendra K. Goswami, Baidyanath Chakravarty, Syed N. Kabir

Journal Articles: Cellular & Integrative Physiology

The management of recurrent pregnancy loss (RPL) still remains a great challenge, and women with polycystic ovarian syndrome (PCOS) are at a greater risk for spontaneous abortion. Treatment with low-molecular-weight heparin (LMWH) has become an accepted treatment option for women with RPL; however, the subgroup of women, who are likely to respond to LMWH, has not been precisely identified. The present study evaluated the efficacy of LMWH with reference to PCOS and associated metabolic phenotypes including hyperhomocysteinemia (HHcy), insulin resistance (IR) and obesity. This prospective observational study was conducted at Institute of Reproductive Medicine, Kolkata, India. A total of 967 …

The Science (And Pseudoscience) Of Dna Profiling, Dan E. Krane

Biological Sciences Faculty Publications

No abstract provided.

Nf1 Loss And Ras Hyperactivation In Oligodendrocytes Induce Nos-Driven Defects In Myelin And Vasculature, Debra A. Mayes, Tilat A. Rizvi, Haley E. Titus-Mitchell, Rachel Oberst, Georgianne M. Ciraolo, Charles V. Vorhees, Andrew P. Robinson, Stephen D. Miller, Jose A. Cancelas, Anat O. Stemmer-Rachamimov, Nancy Ratner

Neuroscience, Cell Biology & Physiology Faculty Publications

Patients with neurofibromatosis type 1 (NF1) and Costello syndrome Rasopathy have behavioral deficits. In NF1 patients, these may correlate with white matter enlargement and aberrant myelin. To model these features, we induced Nf1 loss or HRas hyperactivation in mouse oligodendrocytes. Enlarged brain white matter tracts correlated with myelin decompaction, downregulation of claudin-11, and mislocalization of connexin-32. Surprisingly, non-cell-autonomous defects in perivascular astrocytes and the blood-brain barrier (BBB) developed, implicating a soluble mediator. Nitric oxide (NO) can disrupt tight junctions and gap junctions, and NO and NO synthases (NOS1-NOS3) were upregulated in mutant white matter. Treating mice with the NOS inhibitor …

Maternal Genital Tract Colonisation By Group-B Streptococcus: A Hospital Based Study, Nida Najmi, Rozina Sikandar, Nadeem F. Zuberi, Imtiaz Jehan

Department of Obstetrics & Gynaecology

Objectives: To determine the prevalence of Group B Streptococcus genital tract infection in pregnant women and to determine the risk factors for its colonisation.
Methods: The cross-sectional study was conducted at the Aga Khan University Hospital, Karachi and Sobhraj Hospital, Karachi, from May to August 2007. Pregnant women at 35-37 weeks gestation attending antenatal clinic at these hospitals constituted the study population. Based on stratified sampling, 405 patients were recruited. High vaginal swabs of these patients were taken in order to calculate the prevalence of infection at each hospital. Logistic regression was used to evaluate the risk factor association. SPSS …

Role Of Vimf In Gingipain Maturation In Porphyromonas Gingivalis, Arun S. Muthiah

Loma Linda University Electronic Theses, Dissertations & Projects

Gingipain activity in Porphyromonas gingivalis, the major etiological agent in adult periodontitis, is post-translationally regulated by unique Vim proteins including VimF, a putative glycosyltransferase. To ascertain the VimF mediated phenotype we first inactivated the vimF gene in P. gingivalis ATCC 33277 (FLL476), a less virulent fimbriated strain. We observed that the vimF-defective mutant (FLL476) showed a phenotype similar to that of the vimF-defective mutant (FLL95) in the P. gingivalis W83 background. While hemagglutination was not detected and autoaggregationn was reduced, biofilm formation was increased in FLL476. Also, invasive capacity decreased for this mutant. Furthermore, fimbrial structures were missing in FLL476, …

Conservation Of Structure And Mechanism By Trm5 Enzymes., Thomas Christian, Howard Gamper, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

Enzymes of the Trm5 family catalyze methyl transfer from S-adenosyl methionine (AdoMet) to the N¹ of G37 to synthesize m¹ G37-tRNA as a critical determinant to prevent ribosome frameshift errors. Trm5 is specific to eukaryotes and archaea, and it is unrelated in evolution from the bacterial counterpart TrmD, which is a leading anti-bacterial target. The successful targeting of TrmD requires detailed information on Trm5 to avoid cross-species inhibition. However, most information on Trm5 is derived from studies of the archaeal enzyme Methanococcus jannaschii (MjTrm5), whereas little information is available for eukaryotic enzymes. Here we use human Trm5 (Homo sapiens; HsTrm5) …

Functional Characterization Of Crip1a Knockout Mice, Joanna Jacob

Theses and Dissertations

CB1 cannabinoid receptors are G-protein-coupled receptors that mediate the central nervous system (CNS) effects of marijuana and endocannabinoids. Recently, cannabinoid receptor interacting protein 1a (CRIP1a) was discovered as a novel protein that binds to the CB1 receptor C-terminus and inhibits CB1 receptor activity without affecting CB1 expression. This thesis investigated the functions of CRIP1a by characterizing the first CRIP1a knockout (KO) mouse line. The absence of CRIP1a was confirmed in KO mice using quantitative PCR and immunoblotting. I hypothesized that CRIP1a KO mice would exhibit enhanced CB1 receptor-mediated G-protein activity in the CNS, as well as cannabimemetic phenotypes and enhanced …

The Drug Facts Box: Improving The Communication Of Prescription Drug Information, Lisa M. Schwartz, Steven Woloshin

Dartmouth Scholarship

Communication about prescription drugs ought to be a paragon of public science communication. Unfortunately, it is not. Consumers see $4 billion of direct-to-consumer advertising annually, which typically fails to present data about how well drugs work. The professional label—the Food and Drug Administration's (FDA) mechanism to get physicians information needed for appropriate prescribing—may also fail to present benefit data. FDA labeling guidance, in fact, suggests that industry omit bene

Regulation Of Cell Death By Transfer Rna., Ya-Ming Hou, Xiaolu Yang

Department of Biochemistry and Molecular Biology Faculty Papers

SIGNIFICANCE: Both transfer RNA (tRNA) and cytochrome c are essential molecules for the survival of cells. tRNA decodes mRNA codons into amino-acid-building blocks in protein in all organisms, whereas cytochrome c functions in the electron transport chain that powers ATP synthesis in mitochondrion-containing eukaryotes. Additionally, in vertebrates, cytochrome c that is released from mitochondria is a potent inducer of apoptosis, activating apoptotic proteins (caspases) in the cytoplasm to dismantle cells. A better understanding of both tRNA and cytochrome c is essential for an insight into the regulation of cell life and death.

RECENT ADVANCES: A recent study showed that the …

Calpain-2 Compensation Promotes Angiotensin Ii-Induced Ascending And Abdominal Aortic Aneurysms In Calpain-1 Deficient Mice, Venkateswaran Subramanian, Jessica J. Moorleghen, Anju Balakrishnan, Deborah A. Howatt, Athar H. Chishti, Haruhito A. Uchida

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND AND OBJECTIVE: Recently, we demonstrated that angiotensin II (AngII)-infusion profoundly increased both aortic protein and activity of calpains, calcium-activated cysteine proteases, in mice. In addition, pharmacological inhibition of calpain attenuated AngII-induced abdominal aortic aneurysm (AA) in mice. Recent studies have shown that AngII infusion into mice leads to aneurysmal formation localized to the ascending aorta. However, the precise functional contribution of calpain isoforms (-1 or -2) in AngII-induced abdominal AA formation is not known. Similarly, a functional role of calpain in AngII-induced ascending AA remains to be defined. Using BDA-410, an inhibitor of calpains, and calpain-1 genetic deficient mice, …

Osteopontin Expression During The Acute Immune Response Mediates Reactive Synaptogenesis And Adaptive Outcome, Julie Chan

Theses and Dissertations

Traumatic brain injury (TBI) is a worldwide epidemic as the number of victims living with the resulting cognitive and physical impairment continues to rise, principally due to limited treatment options which fail to address its multifaceted sequelae. By approaching TBI therapy from a molecular standpoint, we have the opportunity to develop a better understanding of the mechanisms which prevent effective recovery. With this information, we can move toward the identification of novel therapeutic treatments which target specific molecules to improve patient outcome following TBI. Here, we have focused on the therapeutic potential of osteopontin (OPN), an extracellular matrix (ECM) protein …

Prophylactic Vs. Therapeutic: Dna Vaccine To Metastatic Colorectal Cancer Using Molecular Marker Guanylyl Cyclase-C, Anmol Khurana, Msii

Summer Training Program in Cancer Immunotherapy

The role of heat-stable enterotoxin receptor guanylyl cyclase C (GCC) is well known for its aberrant chloride conductance in the intestinal epithelium in response to bacterial infection. Recently, its use as a molecular marker to detect metastatic colon cancer has grown, as has its use as oral hormone therapy for tumor suppression. This study investigates the preliminary stages of a DNA dendritic cell-based vaccine development specific to targeting guanylyl cyclase in systemic tissues. Construction of the plasmid as well as its transduction to Class I MHC molecules in antigen-presenting dendritic cells is examined. Future exploration includes a comparative assessment of …

Unraveling The Mechanism Of 2,4-Dinitrofluorobenzene-Associated Cell Death, Franklin Thelmo

Summer Training Program in Cancer Immunotherapy

The mechanism by which the hapten 2,4-dinitrophenyl (DNP) mediates cell death is unclear according to current literature. To determine how DNP mediates death in the B16F10 murine melanoma cell line in vitro, cells were modified with 2,4-dinitro-1-fluorobenzene (DNFB). Following modification, cell lysates were collected and analyzed via Western blottings with known apoptotic or necrotic markers. Our results indicated that DNFB treated cells do not express the apoptotic marker Cleaved Caspase-3 and have no change in levels of the necrotic marker Cyclophilin A. We conclude that DNFB is not inducing apoptosis in B16F10 cells. Future research will further examine the …

Nanotubes As Mitochondrial Uncouplers, Patrick G. Sullivan

Neuroscience Faculty Patents

A method of uncoupling mitochondria in a subject including administering nanotubes to the subject in a therapeutically effective amount, wherein the nanotubes are self-rectifying is provided. A method of decreasing reactive oxygen species and decreasing detrimental loading of Ca²⁺ into mitochondria is provided, including administering a pharmaceutically effective amount of nanotubes into the subject. A method of reducing weight, treating cancer, reducing the effects of traumatic brain injury, or reducing the effects of ageing, in a subject including administering a pharmaceutically effective amount of nanotubes into the subject is also provided.

2013 Annual Meeting Program

Journal of the South Carolina Academy of Science

No abstract provided.

Modulation Of Bax/Bak Dependent Apoptosis By Sirtuin 3 And Mitochondrial Permeability Transition By Sirtuin 4, Manish Verma

Graduate School of Biomedical Sciences Theses and Dissertations

Mitochondria are dynamic organelles that regulate a myriad of cellular functions, including energy production and metabolic regulation. Mitochondria are also a critical regulator of cell death signaling cascades modulating both apoptotic and necrotic cell death. However, what determines which cell death pathway is activated is still unclear. The mitochondrial/intrinsic pathway of apoptosis is dependent on the activation of pro-apoptotic proteins, Bax and Bak, which induce mitochondrial outer membrane permeabilization (MOMP). Once the integrity of outer mitochondrial membrane (OMM) is compromised, pro-apoptotic intermembrane space proteins like cytochrome c, Smac/Diablo, Omi/HtrA2 and AIF are released into the cytoplasm, which activates the post-mitochondrial …

Effects Of Prior Acute Exercise On Circulating Cytokine Concentration Responses To A High-Fat Meal, Josef Brandauer, Rian Q. Landers-Ramos, Nathan T. Jenkins, Espen E. Spangenburg, James M. Hagberg, Steven J. Prior

Health Sciences Faculty Publications

High-fat meal consumption alters the circulating cytokine profile and contributes to cardiometabolic diseases. A prior bout of exercise can ameliorate the triglyceride response to a high-fat meal, but the interactive effects of exercise and high-fat meals on cytokines that mediate cardiometabolic risk are not fully understood. We investigated the effects of prior exercise on the responses of circulating tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), IL-8, leptin, retinol-binding protein 4 (RBP4), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt-1) to a high-fat meal. Ten healthy men were studied before …

Nutri One-On-One: The Assessment And Evaluation Of A Single One-On-One Nutritional Coaching In Patients Affected By Metabolic Syndrome, Jennifer L. King

PCOM Biomedical Studies Student Scholarship

The Nutri One-on-One Program's aim was to positively modify participants' nutritional habits and lifestyles through a brief one-on-one health coaching session, which was conducted within a primary healthcare setting at the Philadelphia College of Osteopathic Medicine's Clinics. It is documented that 70% of deaths in the U.S. result from complications secondary to chronic diseases of metabolic syndrome. The participants were selected by physicians and classified as suffering from one or more of the five indicators of metabolic syndrome: abdominal obesity, elevated serum triglycerides, low HDL-cholesterol, elevated blood pressure, and insulin resistance. Evidence shows that health coaching positively assists individuals in …