Life Sciences Commons^™

Microglial Activation Decreases Retention Of The Protease Inhibitor Saquinavir: Implications For Hiv Treatment, Shannon Dallas, Michelle L. Block, Deborah M. Thompson, Marcelo G. Bonini, Patrick T. Ronaldson, Reina Bendayan, David S. Miller

Anatomy and Neurobiology Publications

Background

Active HIV infection within the central nervous system (CNS) is confined primarily to microglia. The glial cell compartment acts as a viral reservoir behind the blood-brain barrier. It provides an additional roadblock to effective pharmacological treatment via expression of multiple drug efflux transporters, including P-glycoprotein. HIV/AIDS patients frequently suffer bacterial and viral co-infections, leading to deregulation of glial cell function and release of pro-inflammatory mediators including cytokines, chemokines, and nitric oxide.

Methods

To better define the role of inflammation in decreased HIV drug accumulation into CNS targets, accumulation of the antiretroviral saquinavir was examined in purified cultures of rodent …

A Macrophysiological Analysis Of Energetic Constraints On Geographic Range Size In Mammals, Salvatore J. Agosta, Joseph Bernado, Gerardo Ceballos, Michael A. Steele

Biology Publications

Physiological processes are essential for understanding the distribution and abundance of organisms, and recently, with widespread attention to climate change, physiology has been ushered back to the forefront of ecological thinking. We present a macrophysiological analysis of the energetics of geographic range size using combined data on body size, basal metabolic rate (BMR), phylogeny and range properties for 574 species of mammals. We propose three mechanisms by which interspecific variation in BMR should relate positively to geographic range size: (i) Thermal Plasticity Hypothesis, (ii) Activity Levels/Dispersal Hypothesis, and (iii) Energy Constraint Hypothesis. Although each mechanism predicts a positive correlation between …

Characterization And Generation Of Male Courtship Song In Cotesia Congregata (Hymenoptera: Braconidae), Justin P. Bredlau, Yasha J. Mohajer, Timothy M. Cameron, Karen M. Hester, Michael L. Fine

Biology Publications

Background

Male parasitic wasps attract females with a courtship song produced by rapid wing fanning. Songs have been described for several parasitic wasp species; however, beyond association with wing fanning, the mechanism of sound generation has not been examined. We characterized the male courtship song of Cotesia congregata (Hymenoptera: Braconidae) and investigated the biomechanics of sound production.

Methods and Principal Findings

Courtship songs were recorded using high-speed videography (2,000 fps) and audio recordings. The song consists of a long duration amplitude-modulated “buzz” followed by a series of pulsatile higher amplitude “boings,” each decaying into a terminal buzz followed by a …

The E. Coli Effector Protein Nlef Is A Caspase Inhibitor, Sonja Blasche, Mario Mortl, Holger Steuber, Gabriella Siszler, Shahista Nisa, Frank Schwarz, Inna Lavrik, Thomas M. A. Gronewold, Klaus Maskos, Michael S. Donnenberg, Dirk Ullmann, Peter Uetz, Manfred Kogl

Study of Biological Complexity Publications

Enterohemorrhagic and enteropathogenic E. coli (EHEC and EPEC) can cause severe and potentially life-threatening infections. Their pathogenicity is mediated by at least 40 effector proteins which they inject into their host cells by a type-III secretion system leading to the subversion of several cellular pathways. However, the molecular function of several effectors remains unknown, even though they contribute to virulence. Here we show that one of them, NleF, binds to caspase-4, -8, and -9 in yeast two-hybrid, LUMIER, and direct interaction assays. NleF inhibits the catalytic activity of the caspases in vitro and in cell lysate and prevents apoptosis in …

Biosynthesis Of Vitamins And Cofactors In Bacterium-Harbouring Trypanosomatids Depends On The Symbiotic Association As Revealed By Genomic Analyses, Cecilia C. Klein, Joao M. P. Alves, Myrna G. Serrano, Gregory A. Buck, Ana T. R. Vasconcelos, Marie-France Sagot, Marta M. G. Teixeira, Emey P. Camargo, Maria C. M. Motta

Study of Biological Complexity Publications

Some non-pathogenic trypanosomatids maintain a mutualistic relationship with a betaproteobacterium of the Alcaligenaceae family. Intensive nutritional exchanges have been reported between the two partners, indicating that these protozoa are excellent biological models to study metabolic co-evolution. We previously sequenced and herein investigate the entire genomes of five trypanosomatids which harbor a symbiotic bacterium (SHTs for Symbiont-Haboring Trypanosomatids) and the respective bacteria (TPEs for Trypanosomatid Proteobacterial Endosymbiont), as well as two trypanosomatids without symbionts (RTs for Regular Trypanosomatids), for the presence of genes of the classical pathways for vitamin biosynthesis. Our data show that genes …

Mexican Health Paradox, Merit George

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Despite the broad array of research that exists on the Hispanic health paradox, no single explanation has been marked as the dominant reason for the disparities in life expectancy that exist between Mexican Americans and other Hispanic and non-Hispanic ethnic groups. This indicates that researchers must adopt a more open perspective that examines the influence of multidimensional factors that integrate culture, religious tradition, and lifestyle. The purpose of the current study is to 1) readily define the paradox and provide a thorough review of existing literature on the topic; 2) suggest a transition from exploring statistical explanations of the paradox …

Genetic Interaction Influenced By Fluvastatin And Tgfb, Rebekah Rifareal

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

I was looking for an opportunity to network with researchers at VCU and found this program that would provide the perfect atmosphere to do so. The added benefit of HERO was that I also got the opportunity to network with other undergraduates interested in research from VCU as well as other institutions.

Sphingosine-1-Phosphate And Fingolimod (Fty720) Regulate Icl,Swell In Hl-1 Cardiac Myocytes Via Intracellular Binding And Mitochondrial Ros Production, Pooja Desai

Theses and Dissertations

Swelling-activated Cl− current (ICl,swell) is an outwardly-rectifying current that plays an important role in cardiac electrical activity, cellular volume regulation, apoptosis, and acts as a potential effector of mechanoelectrical feedback. Persistent activation of ICl,swell has been observed in models of cardiovascular disease. We previously suggested sphingosine-1-phosphate (S1P) activates volume-sensitive Cl- current (ICl,swell) by ROS-dependent signaling. S1P and its analog, FTY720 (fingolimod), primarily act via G-protein coupled receptors (S1PR; S1PR1-3 in heart), but several intracellular S1P ligands are known. We investigated how these agents regulate ICl,swell. ICl,swell was elicited by bath S1P (500 nM), FTY720 (S1PR1,3 agonist; 10 μM), and SEW2871 …

Calcium/Calmodulin-Dependent Protein Kinase Ii Beta (Camkiiβ): A Regulator Of Oligodendrocyte Maturation And Myelination, Christopher Waggener

Theses and Dissertations

Oligodendrocytes are cells located in the central nervous system (CNS) that are responsible for the production of the lipid rich membrane, myelin. Myelin and the process of making and wrapping myelin around an axon (also known as myelination) are critical for normal development since they ensure proper signal conduction in the vertebrate CNS. The loss or damage of this myelin, which is typically associated with the demyelinating disease multiple sclerosis (MS), is associated with improper axonal protection along with disrupted nerve signaling which can lead to a variety of different debilitating phenotypic responses. It has been shown that there are …

Hormone Epimers Regulate Er Stress And Core Regulatory Genes: Network Analysis With Applications To Glioma And Chronic Pressure Ulcers, Thomas L. Shaak

Theses and Dissertations

DHEA has been determined to have medically significant activity and is the parent compound to the more active metabolites; 17α-AED, 17β-AED and 17β-AET, which exhibit strong biological activity that has been attributed to androgenic, estrogenic or anti-glucocorticoid activity in vivo and in vitro. This study compared DHEA, 17α-AED, 17β-AED and 17β-AET for their ability to activate the human AR, ER and GR receptors and determine the relative androgenicity, estrogenicity and glucocorticoid activity. The results show that, at the receptor level, these androstene hormones are weak AR and even weaker ER activators. Direct androstene hormone activation of the human AR, ERα, …

The Metabolic Transitions Regulated By The Estrogen-Related Receptor (Err) In Drosophila Melanogaster, Yan Li

Theses and Dissertations

In multicellular organism, bioenergetic metabolism is strictly regulated toward efficient generation of ATP. However, in certain situations, such as in limiting oxygen or in the rapidly proliferating system like growing juvenile or cancer cells, organisms apply the metabolic strategy that favors the production of biomass (e.g., nucleotides, amino acids, and lipids) over efficiency of ATP generation. The conserved estrogen-related receptors (ERRs) are master regulators in controlling metabolic homeostasis, and good candidates for mediating the metabolic transition induced by hypoxia and development. First, we investigate how dERR influences hypoxic adaptation in Drosophila melanogaster. We find that dERR is required for a …

Life History Analysis Of James River Atlantic Sturgeon (Acipenser Oxyrinchus Oxyrinchus) With Implications For Management And Recovery Of The Species, Matthew Balazik

Theses and Dissertations

Sturgeon species (family Acipenseridae) are threatened globally due to habitat destruction, pollution, and overfishing. The Atlantic sturgeon Acipenser oxyrinchus oxyrinchus was listed as a federally endangered species in 2012. Atlantic sturgeon have a complex life history that utilizes a wide range of habitats. Timing of life history varies in different areas requiring each population to be studied. Very little work has been published on Atlantic sturgeon reproduction in the James River, Virginia. To aid the recovery of James River Atlantic sturgeon, aspects of life history need to be addressed. To increase understanding of Atlantic sturgeon life history a length at …

Growth Gone Awry: Exploring The Role Of Embryonic Liver Development Genes In Hcv Induced Cirrhosis And Hepatocellular Carcinoma, Martha K. Behnke

Theses and Dissertations

Introduction and methods: Hepatocellular carcinoma (HCC) remains a difficult disease to study even after a decade of genomic analysis. Metabolic and cell-cycle perturbations are known, large changes in tumors that add little to our understanding of the development of tumors, but generate “noise” that obscures potentially important smaller scale expression changes in “driver genes”. Recently, some researchers have suggested that HCC shares pathways involving the master regulators of embryonic development. Here, we investigated the involvement and specificity of developmental genes in HCV-cirrhosis and HCV-HCC. We obtained microarray studies from 30 patients with HCV-cirrhosis and 49 patients with HCV-HCC and compared …

Novel Strategies To Improve Metabolic Parameters And Precondition Diabetic Hearts Against Ischemia/Reperfusion Injury, Amit Varma

Theses and Dissertations

Insulin resistance and chronic hyperglycemia promote vascular damage, increase circulating levels of inflammatory cytokines and lead to increased morbidity and mortality. MicroRNAs (miRs) -103/107 have been shown to negatively regulate insulin sensitivity and glucose homeostasis. Based on complimentary binding profiles, the downstream target gene of miR-103/107 is caveolin-1 (Cav-1). We hypothesized that daily administration of the phosphodiesterase-5 inhibitor tadalafil (TAD) ± the curcumin analogue (HO-3867) will attenuate inflammation, improve metabolic parameters and reduce infarct size after ischemia/reperfusion injury (IRI). Furthermore, we propose that TAD therapy will reduce myocardial expression of miR-103/107 and increase mRNA and protein levels of its target …

Regulation Of Excitation-Contraction And Excitation-Transcription Coupling In Gastrointestinal Smooth Muscle By Caveolin-1, Sayak Bhattacharya

Theses and Dissertations

Caveolae are integral part of the smooth muscle membrane and caveolins, the defining proteins of caveolae, act as scaffolding proteins for several G protein-coupled receptor signaling molecules and regulate cellular signaling through direct and indirect interactions with signaling proteins. Caveolin-1 is the predominant isoform in the smooth muscle and drives the formation of caveolae. However, little is known about the role of caveolin-1 in the regulation of excitation-contraction and excitation-transcription coupling in gastrointestinal smooth muscle. In the present study we have characterized muscarinic m2 and m3 receptor signaling in gastric smooth muscle and tested the hypothesis that caveolin-1 positively regulates …

Mutant P53 Regulation Of Cxc-Chemokine Expression In Head And Neck Squamous Cell Carcinoma, Brittany Field

Theses and Dissertations

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common type of cancer in the western hemisphere with a five-year survival rate of only 50% for patients with a localized tumor, which decreases significantly to as low as 5% for those patients with tumors that have metastasized to distant sites of the body. It has been found that both mutant p53 and epidermal growth factor receptor (EGFR) signaling pathways function to increase the expression of CXCL5, which has been identified as a key mediator in the process of tumor metastasis. Previous data from our lab suggested that the …

Gβγ Acts At An Inter-Subunit Cleft To Activate Girk1 Channels, Rahul Mahajan

Theses and Dissertations

Heterotrimeric guanine nucleotide-binding proteins (G-proteins) consist of an alpha subunit (Gα) and the dimeric beta-gamma subunit (Gβγ). The first example of direct cell signaling by Gβγ was the discovery of its role in activating G-protein regulated inwardly rectifying K+ (GIRK) channels which underlie the acetylcholine-induced K+ current responsible for vagal inhibition of heart rate. Published crystal structures have provided important insights into the structures of the G-protein subunits and GIRK channels separately, but co-crystals of the channel and Gβγ together remain elusive and no specific reciprocal residue interactions between the two proteins are currently known. Given the absence of direct …

Characterization Of Microsatellite Loci And Pilot Population Genetic Analysis In Hickory Shad, Alosa Mediocris, Fnu Vishakha

Theses and Dissertations

The hickory shad (Alosa mediocris) is a relatively understudied species of the anadromous fish sub-family Alosinae. This study, the first population genetic analysis of this species, employed 12 neutral microsatellite loci to estimate genetic diversity and population structure in tributaries of lower Chesapeake Bay, Virginia including James River and its tributaries (Appomattox and Chickahominy Rivers), Rappahannock River, and Pamunkey River. Genetic variation was extremely low. Estimates of observed heterozygosity were lower than expected heterozygosity. Significant population structure was detected among the six samples (FST = 0.093, p = 0.01). Effective population sizes were low (Ne ranged from 2 to 134). …

Purification And Reconstitution Into Planar Bilayers Of The Human Dopamine Transporter, Yoori Kim

Theses and Dissertations

The human dopamine transporter (hDAT) provides the primary mechanism for dopamine clearance in synapses and thus facilitates the regulation of dopaminergic functions in cognition and reward. It is the molecular target of many centrally-active agents including amphetamines and cocaine. Therefore, an understanding of hDAT function and its modulation by these therapeutic drugs and drugs of abuse can provide insight into the mechanisms of abuse and addiction. In the presented studies, hDAT is tagged with a hexahistidine construct and heterologously expressed in Xenopus laevis oocytes. The plasma membranes are isolated, solubilized, and applied to a Nickel affinity column to obtain purified …

Combinatorial Analysis Of Tumorigenic Micrornas Driving Prostate Cancer, William Budd

Theses and Dissertations

Prostate cancer is the leading non-cutaneous malignancy affecting men in the United States. One in every six men will be affected by prostate cancer. Due to the high incidence of prostate cancer, there is a need to develop biomarkers capable of identifying tumors from benign prostatic lesions. miRNAs are small molecules that regulate protein translation and impact cellular integrity when dysregulated. It is widely thought that miRNAs have the potential to serve as biomarkers. This study utilizes a unique combinatorial analysis of miRNA dysregulation to identify key miRNAs involved in prostate tumor initiation, progression and metastasis. Numerous dysregulated miRNAs potentially …

Ocean Acidification: Understanding The Coastal Carbon Pump In A High Co2 World, Rachel Cooper

Theses and Dissertations

Since the 1800s, carbon dioxide emissions due to human activities have contributed significantly to the amount of carbon in the atmosphere. Approximately a third of this carbon is absorbed by the ocean, through air-sea fluxes at the ocean surface (Sabine, 2004). Increased CO2 has changed the carbon chemistry of the ocean and hence the pH. pH is expected to drop by 0.4 by the year 2100. It is unclear how this lower pH will affect carbon cycling and sequestration with respect to the biological carbon pump. Most studies have focused on open ocean phytoplankton or bacterial communities in large, stationary …

Sorafenib Enhances Pemetrexed-Induced Cytotoxicity Through And Autophagy-Dependent Mechanism In Cancer Cells, Bareford Mary

Theses and Dissertations

Acquired cellular resistance to traditional chemotherapeutics is a common obstacle in the treatment of most cancer cell types. This resistance occurs as a result of changes in the underlying molecular mechanisms of disease progression. The development of novel chemotherapeutic approaches designed to enhance the efficacy of protypical anti-cancer drugs is important in order to overcome this issue. Such approaches will aid in understanding the biomolecular phenomena responsible for drug resistance and disease progression. Combining signaling pathway inhibitors has become an effective strategy for enhancing tumor cell death by targeting multiple pathways known to regulate cell survival. Pemetrexed, an FDA-approved anti-folate …

Spag16 Is A Bifunctional Gene Regulating Male Fertility, David R. Nagarkatti-Gude

Theses and Dissertations

SPAG16 is the murine orthologue of Chlamydomonas reinhardtii PF20, a protein known to be essential to the structure and function of the “9 + 2” axoneme. The “9 + 2” axoneme provides the cytoskeletal core of all eukaryotic motile cilia and flagella. In Chlamydomonas, the Pf20 gene encodes a single protein present in the central pair of the axoneme. Loss of Pf20 prevents central pair assembly and results in flagellar paralysis. The murine Spag16 gene encodes two proteins. While 71 kDa SPAG16L is found in all murine cells with motile cilia or flagella, 35 kDa SPAG16S transcript and protein are …

Effects Of Leaf Litter Diversity On Nutrients And Mosquito Communities In Neotropical Artificial Tree Holes, Rachel Komosinski

Theses and Dissertations

Inputs from terrestrial habitats to aquatic habitats are important for structuring aquatic communities. Terrestrial producer diversity in the tropics may decline due to anthropogenic causes. I investigated how tree diversity affects aquatic communities. We used leaves from three timber-producing species (Dalbergia retusa, Pachira quinata, and Tectona grandis) to test the effects of leaf litter species composition and richness on invertebrate aquatic communities in Gamboa, Panama. We quantified macroinvertbrate species richness and abundances, leaf litter mass loss, and dissolved carbon to nitrogen ratios (C:N) after 4 weeks. We found that litter types differed in breakdown and C:N. Tectona grandis had lower …

Characterizing The Interaction Between Ve-Ptp, Tie2 And Ve-Cadherin, Sharif Ossai Muhammad

Theses and Dissertations

Many signaling pathways have been shown to be involved in the formation of the vascular system. Among them are the endothelial specific receptor families such as VEGF, Ang/Tie, as well as other signaling pathways such as semaphorins, which are also involved, in axonal guidance. It is known that the interaction between receptor tyrosine kinase, Tie2, VE-Cadherin, and VE-PTP mediate endothelial cell quiescence and adhesion. However, the structural basis of these interactions is not well understood. The aim of our study is to characterize the binding interactions between these players. Another important part of our study is describing the cross-talk between …

Using Next Generation Sequencing (Ngs) To Identify And Predict Micrornas (Mirnas) Potentially Affecting Schizophrenia And Bipolar Disorder, Vernell Williamson

Theses and Dissertations

The last decade has seen considerable research focusing on understanding the factors underlying schizophrenia and bipolar disorder. A major challenge encountered in studying these disorders, however, has been the contribution of genetic, or etiological, heterogeneity to the so-called “missing heritability” [1-6]. Further, recent successes of large-scale genome-wide association studies (GWAS) have nonetheless seen only limited advancements in the delineation of the specific roles of implicated genes in disease pathophysiology. The study of microRNAs (miRNAs), given their ability to alter the transcription of hundreds of targeted genes, has the potential to expand our understanding of how certain genes relate to schizophrenia …

Sex-Specific Habitat Use And Responses To Fragmentation In An Endemic Chameleon Fauna, Philip Shirk

Theses and Dissertations

Chameleons are an understudied taxon facing many threats, including collection for the international pet trade and habitat loss and fragmentation. A recent field study reports a highly female-biased sex ratio in the Eastern Arc Endemic Usambara three horned chameleon, Trioceros deremensis, a large, sexually dimorphic species. This species is collected for the pet trade, and local collectors report males bring a higher price because only this sex has horns. Thus, sex ratios may vary due to differential rates of survival or harvesting. Alternatively, they may simply appear to be skewed if differences in habitat use biases detection of the sexes. …

Signal Transduction Effects Induced By Erythropoietin In A Hnscc Model System, Shreya Desai

Theses and Dissertations

Head and Neck Squamous Cell Carcinoma (HNSCC) is an epithelial skin cancer of the upper aerodigestive tract, and is the sixth most common malignancy in the U.S. HNSCC patients undergoing chemotherapy commonly develop anemia, a condition in which the body lacks mature red blood cells (RBCs). Erythropoietin (EPO) is a systemically circulating hormone in the body that regulates the production of RBCs and is applied to treat anemia. Recently, several studies implicated shortened life expectancy of cancer patients by EPO administration. It may be due to an unexpected activation of survival and proliferation pathways of cancer cells by EPO because …

Role Of Fyn And Lyn In Igg-Mediate Immune Responses, Yves Falanga

Theses and Dissertations

Anaphylaxis is a rapid, life-threatening hypersensitivity reaction. Until recently, it was mainly attributed to histamine released by mast cells activated by allergen crosslinking (XL) of FcεRI-bound allergen-specific IgE. However, recent reports established that anaphylaxis could also be triggered by basophil, macrophage and neutrophil secretion of platelet activating factor subsequent to FcγR stimulation by IgG/Ag complexes. I have investigated the contribution of Fyn and Lyn tyrosine kinases to FcγRIIb and FcγRIII signaling in the context of IgG-mediated passive systemic anaphylaxis (PSA). I found that mast cell IgG XL induced Fyn, Lyn, Akt, Erk, p38 and JNK phosphorylation. Additionally, IgG XL of …

The Role Of A And B Vitamins During Orofacial Development Of Xenopus Laevis, Allyson Kennedy

Theses and Dissertations

Orofacial anomalies make up about a third of the 120,000 birth defects each year in the United States. Children born with these abnormalities must undergo immense physical and emotional strain in order to correct the defects. In fact, about $697 million is spent every year surgically treating children with cleft lip and/or cleft palate (2011). In countries where surgery is not an option, this abnormality causes immense difficulties in eating, hearing, speech, and psychosocial development. The causes of cleft lip/palate are extremely complex. Genetics play a role in the anomaly; however, 95% of cleft palate cases are non-syndromic and likely …