Medicine and Health Sciences Commons^™

Reduced Androgen Receptor Expression Accelerates The Onset Of Erbb2 Induced Breast Tumors In Female Mice, Myles C. Hodgson, Garrett Vanostran, Sarah Alghamdi, Robert J. Poppiti, Alexander I. Agoulnik, Irina U. Agoulnik

HWCOM Faculty Publications

Androgen receptor (AR) is commonly expressed in both the epithelium of normal mammary glands and in breast cancers. AR expression in breast cancers is independent of estrogen receptor alpha (ERα) status and is frequently associated with overexpression of the ERBB2 oncogene. AR signaling effects on breast cancer progression may depend on ERα and ERBB2 status. Up to 30% of human breast cancers are driven by overactive ERBB2 signaling and it is not clear whether AR expression affects any steps of tumor progression in this cohort of patients. To test this, we generated mammary specific Ar depleted mice (MARKO) by combining …

Identification Of Anziaic Acid, A Lichen Depside From Hypotrachyna Sp., As A New Topoisomerase Poison Inhibitor, Bokun Cheng, Shugeng Cao, Victor Vasquez, Thirunavukkarasu Annamalai, Giselle Tamayo-Castillo, Yuk-Ching Tse-Dinh

Department of Chemistry and Biochemistry

Topoisomerase inhibitors are effective for antibacterial and anticancer therapy because they can lead to the accumulation of the intermediate DNA cleavage complex formed by the topoisomerase enzymes, which trigger cell death. Here we report the application of a novel enzyme-based high-throughput screening assay to identify natural product extracts that can lead to increased accumulation of the DNA cleavage complex formed by recombinant Yersinia pestistopoisomerase I as part of a larger effort to identify new antibacterial compounds. Further characterization and fractionation of the screening positives from the primary assay led to the discovery of a depside, anziaic acid, from the lichen …

Instability Of Ctg Repeats Is Governed By The Position Of A Dna Base Lesion Through Base Excision Repair, Yanhao Lai, Meng Xu, Zunzhen Zhang, Yuan Liu

Department of Chemistry and Biochemistry

Trinucleotide repeat (TNR) expansions and deletions are associated with human neurodegeneration and cancer. However, their underlying mechanisms remain to be elucidated. Recent studies have demonstrated that CAG repeat expansions can be initiated by oxidative DNA base damage and fulfilled by base excision repair (BER), suggesting active roles for oxidative DNA damage and BER in TNR instability. Here, we provide the first evidence that oxidative DNA damage can induce CTG repeat deletions along with limited expansions in human cells. Biochemical characterization of BER in the context of (CTG)20 repeats further revealed that repeat instability correlated with the position of a base …

Responsiveness Of Voltage-Gated Calcium Channels In Sh-Sy5y Human Neuroblastoma Cells On Quasi-Three-Dimensional Micropatterns Formed With Poly (L-Lactic Acid), Ze-Zhi Wu, Zheng-Wei Wang, Li-Guang Zhang, Zhi-Xing An, Dong-Huo Zhong, Qi-Ping Huang, Mei-Rong Luo, Yan-Jian Liao, Liang Jin, Chen-Zhong Li, William S. Kisaalita

Department of Biomedical Engineering Faculty Publications

Introduction:

In this study, quasi-three-dimensional (3D) microwell patterns were fabricated with poly (l-lactic acid) for the development of cell-based assays, targeting voltage-gated calcium channels (VGCCs).

Methods and materials:

SH-SY5Y human neuroblastoma cells were interfaced with the microwell patterns and found to grow as two dimensional (2D), 3D, and near two dimensional (N2D), categorized on the basis of the cells’ location in the pattern. The capability of the microwell patterns to support 3D cell growth was evaluated in terms of the percentage of the cells in each growth category. Cell spreading was analyzed in terms of projection areas under …

Alterations In Glutathione Levels And Apoptotic Regulators Are Associated With Acquisition Of Arsenic Trioxide Resistance In Multiple Myeloma, Shannon M. Matulis, Alejo A. Morales, Lucy Yehiayan, Kelvin P. Lee, Yong Cai, Lawrence H. Boise

Department of Chemistry and Biochemistry

Arsenic trioxide (ATO) has been tested in relapsed/refractory multiple myeloma with limited success. In order to better understand drug mechanism and resistance pathways in myeloma we generated an ATO-resistant cell line, 8226/S-ATOR05, with an IC50 that is 2–3-fold higher than control cell lines and significantly higher than clinically achievable concentrations. Interestingly we found two parallel pathways governing resistance to ATO in 8226/S-ATOR05, and the relevance of these pathways appears to be linked to the concentration of ATO used. We found changes in the expression of Bcl-2 family proteins Bfl-1 and Noxa as well as an increase in cellular glutathione (GSH) …

Living With Uncertainty: Acting In The Best Interests Of Women, Erica Gollub, Zena Stein

HWCOM Faculty Publications

A recent multi-country study on hormonal contraceptives (HC) and HIV acquisition and transmission among African HIV-serodiscordant couples reported a statistically significant doubling of risk for HIV acquisition among women as well as transmission from women to men for injectable contraceptives. Together with a prior cohort study on African women seeking health services, these data are the strongest yet to appear on the HC-HIV risk. This paper will briefly review the Heffron study strengths and relevant biological and epidemiologic evidence; address the futility of further trials; and propose instead an alternative framework for next steps. The weight of the evidence calls …

Epidemiologic Features Of Vulvovaginal Candidiasis Among Reproductive-Age Women In India, Sujit Rathod, Jeffrey D. Klausner, Karl Krupp, Arthur L. Reingold, Purnima Madhivanan

Department of Epidemiology

Background. Vulvovaginal candidiasis is characterized by curd-like vaginal discharge and itching, and is associated with considerable health and economic costs. Materials and Methods. We examined the incidence, prevalence, and risk factors for vulvovaginal candidiasis among a cohort of 898 women in south India. Participants completed three study visits over six months, comprised of a structured interview and a pelvic examination. Results. The positive predictive values for diagnosis of vulvovaginal candidiasis using individual signs or symptoms were low (<19%). We did not find strong evidence for associations between sociodemographic characteristics and the prevalence of vulvovaginal candidiasis. Women clinically diagnosed with bacterial vaginosis had a higher prevalence of vulvovaginal candidiasis (Prevalence 12%, 95% CI 8.2, 15.8) compared to women assessed to be negative for bacterial vaginosis (Prevalence 6.5%, 95% 5.3, 7.6); however, differences in the prevalence of vulvovaginal candidiasis were not observed by the presence or absence of laboratory-confirmed bacterial vaginosis. Conclusions. For correct diagnosis of vulvovaginal candidiasis, laboratory confirmation of infection with Candida is necessary as well as assessment of whether the discharge has been caused by bacterial vaginosis. Studies are needed of women infected with Candida yeast species to determine the risk factors for yeast’s overgrowth.

Magneto-Electric Nano-Particles For Non-Invasive Brain Stimulation, Kun Yue, Rakesh Guduru, Jeongmin Hong, Ping Liang, Madhavan Nair, Sakhrat Khizroev

HWCOM Faculty Publications

This paper for the first time discusses a computational study of using magneto-electric (ME) nanoparticles to artificially stimulate the neural activity deep in the brain. The new technology provides a unique way to couple electric signals in the neural network to the magnetic dipoles in the nanoparticles with the purpose to enable a non-invasive approach. Simulations of the effect of ME nanoparticles for non-invasively stimulating the brain of a patient with Parkinson’s Disease to bring the pulsed sequences of the electric field to the levels comparable to those of healthy people show that the optimized values for the concentration of …

Identification Of Conserved Splicing Motifs In Mutually Exclusive Exons Of 15 Insect Species, Patricia Buendia, John Tyree, Robert Laredo, Shu-Ning Hsu

School of Computing and Information Sciences

Background: During alternative splicing, the inclusion of an exon in the final mRNA molecule is determined by nuclear proteins that bind cis-regulatory sequences in a target pre-mRNA molecule. A recent study suggested that the regulatory codes of individual RNA-binding proteins may be nearly immutable between very diverse species such as mammals and insects. The model system Drosophila melanogaster therefore presents an excellent opportunity for the study of alternative splicing due to the availability of quality EST annotations in FlyBase.

Methods: In this paper, we describe an in silico analysis pipeline to extract putative exonic splicing regulatory sequences from a multiple …

Review Of The History And Current Status Of Cell-Transplant Approaches For The Management Of Neuropathic Pain, Mary J. Eaton, Yerko Berrocal, Stacey Q. Wolfe, Eva Widerström-Noga

HWCOM Faculty Publications

Treatment of sensory neuropathies, whether inherited or caused by trauma, the progress of diabetes, or other disease states, are among the most difficult problems in modern clinical practice. Cell therapy to release antinociceptive agents near the injured spinal cord would be the logical next step in the development of treatment modalities. But few clinical trials, especially for chronic pain, have tested the transplant of cells or a cell line to treat human disease. The history of the research and development of useful cell-transplant-based approaches offers an understanding of the advantages and problems associated with these technologies, but as an adjuvant …

Potential For Cell-Transplant Therapy With Human Neuronal Precursors To Treat Neuropathic Pain In Models Of Pns And Cns Injury: Comparison Of Hnt2.17 And Hnt2.19 Cell Lines, Mary J. Eaton, Yerko Berrocal, Stacey Q. Wolfe

HWCOM Faculty Publications

Effective treatment of sensory neuropathies in peripheral neuropathies and spinal cord injury (SCI) is one of the most difficult problems in modern clinical practice. Cell therapy to release antinociceptive agents near the injured spinal cord is a logical next step in the development of treatment modalities. But few clinical trials, especially for chronic pain, have tested the potential of transplant of cells to treat chronic pain. Cell lines derived from the human neuronal NT2 cell line parentage, the hNT2.17 and hNT2.19 lines, which synthesize and release the neurotransmitters gamma-aminobutyric acid (GABA) and serotonin (5HT), respectively, have been used to evaluate …

Mutation At The Human D1s80 Minisatellite Locus, Kuppareddi Balamurugan, Martin L. Tracey, Uwe Heine, George C. Maha, George T. Duncan

Department of Biological Sciences

Little is known about the general biology of minisatellites. The purpose of this study is to examine repeat mutations from the D1S80 minisatellite locus by sequence analysis to elucidate the mutational process at this locus. This is a highly polymorphic minisatellite locus, located in the subtelomeric region of chromosome 1. We have analyzed 90,000 human germline transmission events and found seven (7) mutations at this locus. The D1S80 alleles of the parentage trio, the child, mother, and the alleged father were sequenced and the origin of the mutation was determined. Using American Association of Blood Banks (AABB) guidelines, we found …

Postmortem Demonstration Of The Source Of Pulmonary Thromboembolism: The Importance Of The Autopsy, Gina Elhammady, Andrew T. Schubeck, Vicky El-Najjar, Morton J. Robinson

HWCOM Faculty Publications

Periprostatic or paravaginal venous thromboses are rarely considered clinically as sites of clot origin in patients with pulmonary thromboembolism. The majority of emboli have been demonstrated to originate in the veins of the legs. This report raises awareness of pelvic vein thrombosis as a potential source of pulmonary embolism that is rarely considered or detected clinically, and which usually requires postmortem examination for recognition. It also reviews the possible routes emboli may take to reach the lungs.

Impact Of A Comprehensive Nutrition And Lifestyle Education Intervention On Body Weight And Health-Related Outcomes In Morbidly-Obese Hispanic-Americans Following Laparoscopic Roux-En Y Gastric Bypass, Monica Petasne Nijamkin

FIU Electronic Theses and Dissertations

As morbid obesity increasingly affects Hispanic-Americans, the incidence of Roux-en-Y gastric bypass procedures (RYGB) among this population rises. Prospective research on the impact of postoperative educational interventions focused on Hispanic-Americans is needed to prevent premature weight loss plateau, weight regain, nutritional deficiencies, and relapse of obesity-related comorbidities. This randomized-controlled study evaluated the impact of a comprehensive nutrition and lifestyle education intervention (6 biweekly postoperative sessions that incorporated motivational strategies for behavioral change) as compared to a non-comprehensive approach (printed guidelines for healthy lifestyle). The variables to consider are body weight, obesity-related comorbidities (depression, diabetes, dyslipidemia, and others), nutrient status, physical …

Combination Of 16s Rrna Variable Regions Provides A Detailed Analysis Of Bacterial Community Dynamics In The Lungs Of Cystic Fibrosis Patients, Melissa S. Doud, Michael Light, Gisela Gonzalez, Giri Narasimhan, Kalai Mathee

Department of Biological Sciences

Chronic bronchopulmonary bacterial infections remain the most common cause of morbidity and mortality among patients with cystic fibrosis (CF). Recent community sequencing work has now shown that the bacterial community in the CF lung is polymicrobial. Identifying bacteria in the CF lung through sequencing can be costly and is not practical for many laboratories. Molecular techniques such as terminal restriction fragment length polymorphism or amplicon length heterogeneity-polymerase chain reaction (LH-PCR) can provide many laboratories with the ability to study CF bacterial communities without costly sequencing. The aim of this study was to determine if the use of LH-PCR with multiple …

Arsenic Transport By Zebrafish Aquaglyceroporins, Mohamad Hamdi, Marco A. Sanchez, Lauren C. Beene, Qianyong Liu, Scott M. Landfear, Barry P. Rosen, Zijuan Liu

HWCOM Faculty Publications

Background

Arsenic is one of the most ubiquitous toxins and endangers the health of tens of millions of humans worldwide. It is a mainly a water-borne contaminant. Inorganic trivalent arsenic (As^III) is one of the major species that exists environmentally. The transport of As^III has been studied in microbes, plants and mammals. Members of the aquaglyceroporin family have been shown to actively conduct As^III and its organic metabolite, monomethylarsenite (MAs^III). However, the transport of As^III and MAs^III in in any fish species has not been characterized.

Results

In this study, five members …

Comparative Transcriptome Analyses Of Pseudomonas Aeruginosa, Deepak Balasubramanian, Kalai Mathee

HWCOM Faculty Publications

One of the hallmarks of bacterial survival is their ability to adapt rapidly to changing environmental conditions. Niche adaptation is a response to the signals received that are relayed, often to regulators that modulate gene expression. In the post-genomic era, DNA microarrays are used to study the dynamics of gene expression on a global scale. Numerous studies have used Pseudomonas aeruginosa--a Gram-negative environmental and opportunistic human pathogenic bacterium--as the model organism in whole-genome transcriptome analysis. This paper reviews the transcriptome studies that have led to immense advances in our understanding of the biology of this intractable human pathogen. Comparative …

Serial Evolutionary Networks Of Within-Patient Hiv-1 Sequences Reveal Patterns Of Evolution Of X4 Strains, Patrica Buendia, Giri Narasimhan

School of Computing and Information Sciences

Background

The HIV virus is known for its ability to exploit numerous genetic and evolutionary mechanisms to ensure its proliferation, among them, high replication, mutation and recombination rates. Sliding MinPD, a recently introduced computational method [1], was used to investigate the patterns of evolution of serially-sampled HIV-1 sequence data from eight patients with a special focus on the emergence of X4 strains. Unlike other phylogenetic methods, Sliding MinPD combines distance-based inference with a nonparametric bootstrap procedure and automated recombination detection to reconstruct the evolutionary history of longitudinal sequence data. We present serial evolutionary networks as a longitudinal representation …

D1s80 Dna Profiling In Five African Populations, Leslie R. Adrien

FIU Electronic Theses and Dissertations

The highly polymorphic DlS80 locus has no known genetic function. This variable number of tandem repeat (VNTR) has been valuable in forensic identification. We have obtained allelic and genotypic frequencies for five African populations (Benin, Cameroon, Egypt, Kenya and Rwanda), which could be employed as databases to identify individuals.

The polymerase chain reaction, followed by vertical polyacrylamide gel electrophoresis and silver staining was our method of analysis. Allele frequencies were used to infer genetic associations using Phylip 3.5, Principal Component and G-test statistical programs. Tests for Hardy-Weinberg equilibrium were employed. Fst estimates and power of discrimination values were also determined …

Construction And Screening Of A Cdna Library For The C3 Gene(S) Of The Nurse Shark (Ginglymostoma Cirratum), Janette Cristina Builes

FIU Electronic Theses and Dissertations

Mammalian C3 is a complement protein which consists of an α chain (125kDa) and β chain (75kDa) held together by a disulfide bond. The a chain contains a conserved thiolester site which provides the molecule with opsonic properties. The protein is synthesized as a single pro-C3 molecule which is post-translationally modified. C3 genes have been identified in organisms from different phyla, however, the shark C3 gene remains to be cloned. Sequence data from the shark will contribute to understanding further the evolution of this key protein. To obtain additional sequence data for shark C3 genes a cDNA library was constructed …