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Regulation Of Glioma Cell Migration And Proliferation By A Non-Selective Cation Channel., Arun Kumar Rooj

All ETDs from UAB

Two of the most striking features of brain tumors are their unusual ability to robustly proliferate and migrate in the brain. Previous results from our laboratory suggest that glioma cells express a non-selective cation channel that is composed of Epithelial Sodium Channel (ENaC) and Acid Sensing Ion Channel (ASIC) subunits. We hypothesize that this glioma specific current regulates glioma cell migration and proliferation by modulating an intracellular signaling pathway. To test our hypothesis, we have attenuated this cationic conductance by either pharmacological blockers (psalmotoxin-1 and benzamil), or by knocking down expression of a particular subunit of this cross-clade ion channel …

Determinant Of G-Chain Mediated Fc Receptor Signaling, Spandan Shah

All ETDs from UAB

Fc receptors provide an interface between humoral immunity and cellular immunity by binding to the Fc portion of immunoglobulin and mediating effector functions. Cells expressing Fc receptors play a major role in immune complex clearance via phagocytosis, leading to a context dependent pro- or anti-inflammatory environment. Signaling by multi-chain Fc receptor complexes, including FcgRI, FcgRIII, FceRI and FcaRI is mediated by the ITAM-containing common FceRIg (g-chain) subunit. However, despite the use of a common g-chain, different Fc receptor complexes elicit specific cellular programs, suggesting additional layers of regulation of tyrosine based signaling by g-chain. We hypothesized that the unique g-chain …

Neuropathological Alterations In Alzheimer's Disease: An Up Close Look At Sympathetic Sprouting, Amy Renee Nelson

All ETDs from UAB

Pathological hallmarks of AD include neurofibrillary tau tangles, amyloid beta (Abeta) accumulation and cholinergic degeneration. Cholinergic degeneration can be mimicked in rats by lesioning cholinergic neurons in medial septum. Hippocampal cholinergic denervation disrupts retrograde transport of nerve growth factor (NGF), leading to its accumulation, which subsequently triggers sprouting of noradrenergic sympathetic fibers from the superior cervical ganglia into hippocampus. Dr. McMahon's lab previously reported that coincident with this sprouting, there is an increase in cholinergic innervation that correlates with a recovery of M1 muscarinic receptor dependent plasticity at CA3-CA1 synapses and visual cortex. These findings suggest that noradrenergic sympathetic sprouting …

Ash2 Acts As An Ecdysone Receptor Coactivator By Stabilizing The Histone Methyltransferase Trr., Albert Carbonell, Alexander Mazo, Florenci Serras, Montserrat Corominas

Department of Biochemistry and Molecular Biology Faculty Papers

The molting hormone ecdysone triggers chromatin changes via histone modifications that are important for gene regulation. On hormone activation, the ecdysone receptor (EcR) binds to the SET domain-containing histone H3 methyltransferase trithorax-related protein (Trr). Methylation of histone H3 at lysine 4 (H3K4me), which is associated with transcriptional activation, requires several cofactors, including Ash2. We find that ash2 mutants have severe defects in pupariation and metamorphosis due to a lack of activation of ecdysone-responsive genes. This transcriptional defect is caused by the absence of the H3K4me3 marks set by Trr in these genes. We present evidence that Ash2 interacts with Trr …

Molecular Determinants Of Epidermal Growth Factor Binding: A Molecular Dynamics Study., Jeffrey M Sanders, Matthew E Wampole, Mathew L. Thakur, Eric Wickstrom

Department of Biochemistry and Molecular Biology Faculty Papers

The epidermal growth factor receptor (EGFR) is a member of the receptor tyrosine kinase family that plays a role in multiple cellular processes. Activation of EGFR requires binding of a ligand on the extracellular domain to promote conformational changes leading to dimerization and transphosphorylation of intracellular kinase domains. Seven ligands are known to bind EGFR with affinities ranging from sub-nanomolar to near micromolar dissociation constants. In the case of EGFR, distinct conformational states assumed upon binding a ligand is thought to be a determining factor in activation of a downstream signaling network. Previous biochemical studies suggest the existence of both …

The Tip Of The Tail Needle Affects The Rate Of Dna Delivery By Bacteriophage P22., Justin C Leavitt, Lasha Gogokhia, Eddie B Gilcrease, Anshul Bhardwaj, Gino Cingolani, Sherwood R Casjens

Department of Biochemistry and Molecular Biology Faculty Papers

The P22-like bacteriophages have short tails. Their virions bind to their polysaccharide receptors through six trimeric tailspike proteins that surround the tail tip. These short tails also have a trimeric needle protein that extends beyond the tailspikes from the center of the tail tip, in a position that suggests that it should make first contact with the host's outer membrane during the infection process. The base of the needle serves as a plug that keeps the DNA in the virion, but role of the needle during adsorption and DNA injection is not well understood. Among the P22-like phages are needle …

Structural Implications For Selective Targeting Of Parps., Jamin D Steffen, Md, Jonathan Brody, Md, Roger S Armen, Md, John M Pascal, Md

Department of Biochemistry and Molecular Biology Faculty Papers

Poly(ADP-ribose) polymerases (PARPs) are a family of enzymes that use NAD(+) as a substrate to synthesize polymers of ADP-ribose (PAR) as post-translational modifications of proteins. PARPs have important cellular roles that include preserving genomic integrity, telomere maintenance, transcriptional regulation, and cell fate determination. The diverse biological roles of PARPs have made them attractive therapeutic targets, which have fueled the pursuit of small molecule PARP inhibitors. The design of PARP inhibitors has matured over the past several years resulting in several lead candidates in clinical trials. PARP inhibitors are mainly used in clinical trials to treat cancer, particularly as sensitizing agents …

Identification Of Phosphorylation Sites In The Cooh-Terminal Tail Of The Μ-Opioid Receptor., Ying-Ju Chen, Sue Oldfield, Adrian J. Butcher, Andrew B. Tobin, Kunal Saxena, Vsevolod V. Gurevich, Jeffrey L. Benovic, Graeme Henderson, Eamonn Kelly

Department of Biochemistry and Molecular Biology Faculty Papers

Phosphorylation is considered a key event in the signalling and regulation of the μ opioid receptor (MOPr). Here, we used mass spectroscopy to determine the phosphorylation status of the C-terminal tail of the rat MOPr expressed in human embryonic kidney 293 (HEK-293) cells. Under basal conditions, MOPr is phosphorylated on Ser(363) and Thr(370), while in the presence of morphine or [D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO), the COOH terminus is phosphorylated at three additional residues, Ser(356) , Thr(357) and Ser(375). Using N-terminal glutathione S transferase (GST) fusion proteins of the cytoplasmic, C-terminal tail of MOPr and point mutations of the same, we …

Alpha-Synuclein Aggregates Activate The Nlrp3 Inflammasome Following Vesicle Rupture, Rudy Orlando Cedillos

Master's Theses

Parkinson's disease (PD) and related synucleinopathies are progressive neurodegenerative disorders that feature the accumulation of intracellular inclusions known as Lewy bodies (LBs) in the brain. The presynaptic protein α-synuclein is the primary constituent of LBs and has been documented to play a major role in the pathogenesis of synucleinopathies. Recently, aggregated α-synuclein has been implicated in prompting microglia-mediated inflammation, a process associated with the progression of neuronal death in neurodegenerative disorders. Although the mechanisms surrounding the induction of neuroinflammation are not well understood, the recently discovered inflammasome-forming NLR proteins have emerged as regulators of inflammation. In this study, we sought …

P900: A Putative Novel Erp Component That Indexes Counter-Measure Use In The P300-Based Concealed Information Test, John B. Meixner Jr., Elena Labkovsky, J. Peter Rosenfeld, Michael R. Winograd, Michael Winograd, Alexander Sokolovsky, Jeff Weishaar, Tim Ullmann

Scholarly Works

Countermeasures pose a serious threat to the effectiveness of the Concealed Information Test (CIT). In a CIT experiment, Rosenfeld and Labkovsky in Psychophysiology 47(6):1002–1010, (2010) observed a previously unknown positive ERP component at about 900 ms poststimulus at Fz and Cz that could potentially serve as an index of countermeasure use. Here, we explored the hypothesis that this component, termed P900, occurs in response to a signal that no further specific response is required in a trial, and could thus appear in countermeasure users that respond differentially depending on the stimulus that appears. In the present experiments, subjects viewed four …

Histology And Ultrastructure Of Transitional Changes In Skin Morphology In The Juvenile And Adult Four-Striped Mouse (Rhabdomys Pumilio), Eranée Stewart, Moyosore Salihu Ajao, Amadi O. Ihunwo

Brain and Mind Institute

The four-striped mouse has a grey to brown coloured coat with four characteristic dark stripes interspersed with three lighter stripes running along its back. The histological differences in the skin of the juvenile and adult mouse were investigated by Haematoxylin and Eosin and Masson Trichrome staining, while melanocytes in the skin were studied through melanin-specific Ferro-ferricyanide staining. The ultrastructure of the juvenile skin, hair follicles, and melanocytes was also explored. In both the juvenile and adult four-striped mouse, pigment-containing cells were observed in the dermis and were homogeneously dispersed throughout this layer. Apart from these cells, the histology of the …

The Incidence And Aetiology Of Hospitalised Community-Acquired Pneumonia Among Vietnamese Adults: A Prospective Surveillance In Central Vietnam, Kensuke Takahashi, Motoi Suzuki, Le Minh, Nguyen Anh, Luu Thi Huong, Tran Vo Son, Phan Long, Nguyen Thi Ai, Le Tho, Konosuke Morimoto, Paul E. Kilgore, Dang Anh, Koya Ariyoshi, Lay Yoshida

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Lower respiratory tract infection (LRTI) including Community-acquired pneumonia (CAP) is a common infectious disease that is associated with significant morbidity and mortality. The patterns of aetiological pathogens differ by region and country. Special attention must be paid to CAP in Southeast Asia (SEA), a region facing rapid demographic transition. Estimates burden and aetiological patterns of CAP are essential for the clinical and public health management. The purposes of the study are to determine the incidence, aetiological pathogens, clinical pictures and risk factors of community-acquired pneumonia (CAP) in the Vietnamese adult population.

Methods

A prospective surveillance for hospitalised adult …

Intronic Non-Cg Dna Hydroxymethylation And Alternative Mrna Splicing In Honey Bees, Pablo Cingolani, Xiaoyi Cao, Radhika S. Khetani, Chieh-Chun Chen, Melissa Coon, Alya'a Sammak, Aliccia Bollig-Fischer, Susan Land, Yun Huang, Matthew E. Hudson, Mark D. Garfinkel, Sheng Zhong, Gene E. Robinson, Douglas M. Ruden

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Previous whole-genome shotgun bisulfite sequencing experiments showed that DNA cytosine methylation in the honey bee (Apis mellifera) is almost exclusively at CG dinucleotides in exons. However, the most commonly used method, bisulfite sequencing, cannot distinguish 5-methylcytosine from 5-hydroxymethylcytosine, an oxidized form of 5-methylcytosine that is catalyzed by the TET family of dioxygenases. Furthermore, some analysis software programs under-represent non-CG DNA methylation and hydryoxymethylation for a variety of reasons. Therefore, we used an unbiased analysis of bisulfite sequencing data combined with molecular and bioinformatics approaches to distinguish 5-methylcytosine from 5-hydroxymethylcytosine. By doing this, we have performed the first whole …

Early Adolescent Nicotine Exposure Has Long-Lasting Effects On Cocaine-Induced Behaviors In Mice, Mai Alajaji

Theses and Dissertations

Nicotine is one of the most commonly used drugs among adolescent populations. Given the fact that adolescence is a unique developmental stage, during which nicotine has long-term effects on future drug-taking behavior, it is essential to understand how early exposure to nicotine during adolescence may affect the abuse liability of other drugs. We hypothesize that repeated exposure to low doses of nicotine in adolescence induce age-specific enhancement of the rewarding effects of several drugs of abuse in the conditioned place preference (CPP) test. Furthermore, we predict that these changes in behavioral responses are mediated by nicotine-induced brain region-specific increases in …

Attachment Ability And Melanoma Inhibitory Activity Mrna Expression Level Changes In Murine B16-F10 Melanoma Cells Post Nanosecond Electric Pulses, Hongxia Jia

Theses and Dissertations in Biomedical Sciences

The effects of high-voltage nanosecond electric pulses (nsEPs) on metastatic melanoma are still unclear. Hence, we applied one, two, three, and four 300 ns 40 kV/cm pulses to murine B16-F10 melanoma cells. Cell attachment ability was determined by comparing the number of floating cells and the percentage of attached cells. Melanoma inhibitory activity (MIA) is a secretory protein that is highly correlated with the malignancy and metastasis of malignant melanomas. We used MIA as our target to evaluate the effect of nsEPs on metastasis. Pulsed (experimental) and unpulsed (control) cells were incubated at 37°C under a 5% CO₂ atmosphere. …

Pax3 Expression, Protein Modifications And Downstream Target Gene Profiling In Melanocytes And Melanoma Cells, Danielle Bartlett

Theses: Doctorates and Masters

PAX3 is a transcription factor. It plays a major role in the development of melanocytes in the embryo. As a result of alternative splicing, the gene gives rise to eight different transcripts which encode proteins that have differing structures and are therefore likely to activate different downstream target genes. The presence of post-translational modifications has also been shown to alter the functions of the proteins.

PAX3 regulates the maintenance of undifferentiated melanoblasts and mediates pathways involved in proliferation, migration and survival. It has been shown to be expressed in melanoblasts, adult melanocytes, naevi and in most melanoma cells. This implies …

The Effects Of Uv Light On The Antimicrobial Activities Of Cave Actinomycetes, Devon Rule, Naowarat Cheeptham

International Journal of Speleology

The goal of this study was to determine whether actinomycetes isolated from a volcanic cave in western Canada could produce novel antimicrobial compounds against six multidrugresistant pathogens when exposed to UV light. One hundred and seventy-six actinomycete strains isolated from Helmcken Falls Cave, Wells Gray Provincial Park, BC, were screened against six pathogens using the “plug assay” in UV light and no light conditions. Of the 176 strains tested, 100 or 57% of the cave actinomycete strains had antimicrobial activities against the pathogens in 124 different instances: 35 instances when exposed to UV and no light, 30 when exposed to …

Proteolytic Processing Of The Amyloid Precursor Protein During Apoptosis And Cell Cycle: Implications For Alzheimer's Disease, Tina N. Fiorelli

USF Tampa Graduate Theses and Dissertations

Alzheimer's disease is characterized by the presence of amyloid plaques, made up primarily of Aϐ peptides, and neurofibrillary tangles, containing hyperphosphorylated tau. Aϐ is generated by sequential proteolysis of the amyloid precursor protein (APP) by beta and gamma secretases. The leading hypothesis of Alzheimer's disease pathogenesis is the amyloid cascade hypothesis, which suggests that amyloid is central to the disease process. However, tau pathology correlates more closely with cognitive dysfunction and follows a predictable anatomical course through the brain. We hypothesize that if Aϐ is upstream of tau pathology and tau pathology follows this predictable course through the brain, Aϐ …

The Role Of Molecular Chaperones In The Etiology And Treatment Of Psychiatric Diseases In The Elderly, John Clarence O'Leary

USF Tampa Graduate Theses and Dissertations

The elderly are at increased risk for developing psychiatric diseases, which include Alzheimer's disease, depression, anxiety and suicide. The probability of multiple disease comorbidity is also increased in the elderly. At the cellular level, the loss of protein homeostasis is often at the root of disease emergence, and thus the scientific community is searching for ways to help maintain this balance. A vast group of proteins that are paramount to balancing and counterbalancing protein levels is the molecular chaperone protein group, which has evolved a tremendous variety of functions in the cell. They aid in protein trafficking, folding, receptor signaling, …

The Inflammatory Response Initiated By The Spleen To Ischemic Stroke, Hilary Seifert

USF Tampa Graduate Theses and Dissertations

The peripheral immune system plays a role in delayed neural injury after stroke. This response originates from the spleen as splenectomy prior to middle cerebral artery occlusion (MCAO) in rats significantly reduces infarct volume in the brain. This research is based on the hypothesis that inhibiting the splenic response will reduce neurodegeneration after stroke. Studies in animals have implicated lymphocytes as the immune cell type that is detrimental following MCAO. Interferon gamma (IFNγ) has been identified as a pro-inflammatory cytokine that is also detrimental following stroke. IFNγ is important because it activates microglia and macrophages in a pro-inflammatory nature that …

Diet-Induced Ketosis And Calorie Restriction In Mouse Models Of Alzheimer's Pathology, Milene Lara Brownlow

USF Tampa Graduate Theses and Dissertations

Dietary manipulations and their pharmacological outcomes have been increasingly studied in neurodegenerative diseases. However, a systematic comparison among different methods in validated animal models of Alzheimer's disease is made necessary due to several different approaches applied in recent studies. Moreover, despite the large body of evidence on the effects of calorie restriction (CR) and ketogenic diets (KDs) on amyloid pathology, no consistent data is available on the effects of calorie restriction, ketogenic diet or ketone supplements on tau pathology in transgenic models of AD. Moreover, the ketogenic diet used in our studies was custom made with low carbohydrate content and …

Retinal Vascular Biomarkers For Early Detection And Monitoring Of Alzheimer's Disease, Shawn Frost, Yogi Kanagasingam, Hamid Sohrabi, J Vignarajan, P Bourgeat, Olivier Salvado, Victor Villemagne, Christopher Rowe, S Lance Macaulay, Cassandra Szoeke, Kathryn A. Ellis, David Ames, Colin L. Masters, Stephanie Rainey-Smith, Ralph N. Martins

Research outputs 2013

The earliest detectable change in Alzheimer's disease (AD) is the buildup of amyloid plaque in the brain. Early detection of AD, prior to irreversible neurological damage, is important for the efficacy of current interventions as well as for the development of new treatments. Although PiB-PET imaging and CSF amyloid are the gold standards for early AD diagnosis, there are practical limitations for population screening. AD-related pathology occurs primarily in the brain, but some of the hallmarks of the disease have also been shown to occur in other tissues, including the retina, which is more accessible for imaging. Retinal vascular changes …

Multiplex Biomarkers In Blood, Veer Bala Bala Gupta, Ramani Sundaram, Ralph N. Martins

Research outputs 2013

Advances in the field of blood biomarker discovery will help in identifying Alzheimer's disease in its preclinical stage, allowing treatment to be initiated before irreversible damage occurs. This review discusses some recent past and current approaches being taken by researchers in the field. Individual blood biomarkers have been unsuccessful in defining the disease pathology, progression and thus diagnosis. This directs to the need for discovering a multiplex panel of blood biomarkers as a promising approach with high sensitivity and specificity for early diagnosis. However, it is a great challenge to standardize a worldwide blood biomarker panel due to the innate …

Faculty Publications 2012, Lsu Health Sciences Center New Orleans

Historical Faculty Publications

This Faculty bibliography contains 821 publications.

Purpose And Criteria For Blood Smear Scan, Blood Smear Examination, And Blood Smear Review., Gene Gulati, Jinming Song, Alina Dulau Florea, Jerald Gong

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A microscopic examination of an appropriately prepared and well-stained blood smear by a knowledgeable laboratory professional is necessary and clinically useful in a number of circumstances and for a variety of reasons. In this article, an attempt is made to delineate the purpose and criteria for blood smear examination in a variety of circumstances that are encountered in everyday laboratory hematology practice. A blood smear scan serves to at least (a) verify the flagged automated hematology results and (b) determine if a manual differential leukocyte count needs to be performed. Blood smear examination/manual differential leukocyte count with complete blood count …

Ethanol Diverts Early Neuronal Differentiation Trajectory Of Embryonic Stem Cells By Disrupting The Balance Of Lineage Specifiers., Rosa Sánchez-Alvarez, Saurabh Gayen, Rajanikanth Vadigepalli, Helen Anni

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Ethanol is a toxin responsible for the neurodevelopmental deficits of Fetal Alcohol Spectrum Disorders (FASD). Recent evidence suggests that ethanol modulates the protein expression of lineage specifier transcription factors Oct4 (Pou5f1) and Sox2 in early stages of mouse embryonic stem (ES) cell differentiation. We hypothesized that ethanol induced an imbalance in the expression of Oct4 and Sox2 in early differentiation, that dysregulated the expression of associated and target genes and signaling molecules and diverted cells from neuroectodermal (NE) formation.

METHODOLOGY/PRINCIPAL FINDINGS: We showed modulation by ethanol of 33 genes during ES cell differentiation, using high throughput microfluidic dynamic array …

The Contributions Of Hif-Target Genes To Tumor Growth In Rcc., Ting Zhang, Xiaohua Niu, Lili Liao, Eun-Ah Cho, Haifeng Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Somatic mutations or loss of expression of tumor suppressor VHL happen in the vast majority of clear cell Renal Cell Carcinoma, and it's causal for kidney cancer development. Without VHL, constitutively active transcription factor HIF is strongly oncogenic and is essential for tumor growth. However, the contribution of individual HIF-responsive genes to tumor growth is not well understood. In this study we examined the contribution of important HIF-responsive genes such as VEGF, CCND1, ANGPTL4, EGLN3, ENO2, GLUT1 and IGFBP3 to tumor growth in a xenograft model using immune-compromised nude mice. We found that the suppression of VEGF or CCND1 impaired …

Identification Of Potential Synthetic Lethal Genes To P53 Using A Computational Biology Approach, Xiaosheng Wang, Richard Simon

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND:

Identification of genes that are synthetic lethal to p53 is an important strategy for anticancer therapy as p53 mutations have been reported to occur in more than half of all human cancer cases. Although genome-wide RNAi screening is an effective approach to finding synthetic lethal genes, it is costly and labor-intensive.

METHODS:

To illustrate this approach, we identified potentially druggable genes synthetically lethal for p53 using three microarray datasets for gene expression profiles of the NCI-60 cancer cell lines, one next-generation sequencing (RNA-Seq) dataset from the Cancer Genome Atlas (TCGA) project, and one gene expression data from the Cancer …

Biomarkers Of Disease : Concentrations In The Serum Of Women During Natural And Stimulated Ovarian Cycles And During Early Pregnancy, Melissa Stemp

Theses: Doctorates and Masters

Molecular biomarkers are chemical signatures that all cell types possess. They are used in medicine to evaluate both normal biological events and pathogenic processes. A series of biomarkers associated with cancer of the breast, ovaries and other parts of the female reproductive tract and the monitoring of pregnancy were measured in disease‐free women. The biomarkers measured were prostate specific antigen (PSA), CA125, CA15‐3, CA72‐4, and pregnancy associated plasma protein‐a (PAPP‐A). The patterns of change during natural and stimulated ovarian cycles and early pregnancy were investigated to determine if these biomarkers could reflect normal events relating to ovulation and implantation/placentation. In …

Discovery Of New Biomarkers Of Mild Cognitive Impairment And Alzheimer's Disease Risk In Buccal Cells Using Laser Scanning Cytometry, Maxime Francois

Theses: Doctorates and Masters

Previous studies have shown that mild cognitive impairment (MCI) may reflect the early stages of more pronounced neurodegenerative disorders such as Alzheimer’s disease (AD). In clinical practice, patients with AD are not usually identified until the disease has progressed to a stage when primary prevention is no longer possible. Therefore there is a need for a minimally invasive and inexpensive diagnostic to identify those who exhibit cellular pathology indicative of MCI and AD risk so that they can be prioritised for primary prevention. Human buccal cells are accessible in a minimally invasive manner, and exhibit cytological and nuclear morphologies that …