Digital Commons Network^™

Novel Neuroprotective Gsk-3Β Inhibitor Restricts Tat-Mediated Hiv-1 Replication, Irene Guendel, Sergey N. Iordanskiy, Rachel Van Duyne, Kylene Kehn-Hall, Mohammed Saifuddin, Ravi Das, Elizabeth Jaworski, Gavin C. Sampey, Svetlana Senina, Leonard Shultz, Aarthi Narayanan, Chen Hao, Benjamin Lepene, Chen Zeng, Fatah Kashanchi

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The implementation of new antiretroviral therapies targeting transcription of early viral proteins in postintegrated HIV-1 can aid in overcoming current therapy limitations. Using high-throughput screening assays, we have previously described a novel Tat-dependent HIV-1 transcriptional inhibitor named 6-bromoindirubin-3′-oxime (6BIO). The screening of 6BIO derivatives yielded unique compounds that show potent inhibition of HIV-1 transcription. We have identified a second-generation derivative called 18BIOder as an inhibitor of HIV-1 Tat-dependent transcription in TZM-bl cells and a potent inhibitor of GSK-3β kinase in vitro. Structurally, 18BIOder is half the molecular weight and structure of its parental compound, 6BIO. More importantly, we also …

Trans-Activation, Post-Transcriptional Maturation, And Induction Of Antibodies To Herv-K (Hml-2) Envelope Transmembrane Protein In Hiv-1 Infection, Henri-Alexandre Michaud, Miguel De Mulder, Devi Sengupta, Steven G. Deeks, Jeffrey N. Martin, Christopher D. Pilcher, Frederick M. Hecht, Jonah B. Sacha, Douglas F. Nixon

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Human Endogenous Retroviruses (HERVs) comprise about 8% of the human genome and have lost their ability to replicate or to produce infectious particles after having accumulated mutations over time. We assessed the kinetics of expression of HERV-K (HML-2) Envelope mRNA transcript and surface unit (SU) and transmembrane (TM) subunit proteins during HIV-1 infection. We also mapped the specificity of the humoral response to HERV-K (HML-2) Envelope protein in HIV-1 infected subjects at different stages of disease, and correlated the response with plasma viral load.

Results

We found that HIV-1 modified HERV-K (HML-2) Env mRNA expression, resulting in the expression …

Suppression Of Aquaporin, A Mediator Of Water Channel Control In The Carcinogenic Liver Fluke, Opisthorchis Viverrini, Sirikanda Thanasuwan, Supawadee Piratae, Paul J. Brindley, Alex Loukas, Sasithorn Kaewkes, Thewarach Laha

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Opisthorchiasis and Opisthorchis viverrini-associated bile duct cancer represent major public health threats in Thailand and Laos. The tegument of this food borne fluke plays pivotal roles in parasite metabolism, homeostasis and osmoregulation. Excretory/secretory products also pass from the fluke to the biliary environment, products that likely underlie pathogenesis of liver fluke infection. Aquaporins (AQPs), belong to the major intrinsic protein superfamily of integral plasma membrane channel proteins that selectively transport water across cell membranes. AQPs play key roles as water and ion transport channels through the tegument of helminth parasites.

Methods

Here, two forms of AQP mRNAs from the …

Bioclojure: A Functional Library For The Manipulation Of Biological Sequences, Jordan L. Plieskatt, Gabriel Rinaldi, Paul J. Brindley, Xinying Jia, Jeremy Potriquet, Jeffrey M. Bethony, Jason Mulvenna

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Motivation: BioClojure is an open-source library for the manipulation of biological sequence data written in the language Clojure. BioClojure aims to provide a functional framework for the processing of biological sequence data that provides simple mechanisms for concurrency and lazy evaluation of large data sets.

Results: BioClojure provides parsers and accessors for a range of biological sequence formats, including UniProtXML, Genbank XML, fasta and fastq. In addition it provides wrappers for key analysis programs, including BLAST, SignalP, TMHMM and InterProScan, and parsers for analyzing their output. All interfaces leverage Clojure's functional style and emphasize laziness and composability, so that BioClojure, …

Schistosomes And Snails: A Molecular Encounter, Matty Knight, Halime D. Arican-Goktas, Wannaporn Ittiprasert, Edwin C. Odoemelam, Andre N. Miller, Joanna M. Bridger

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Biomphalaria glabrata snails play an integral role in the transmission of Schistosoma mansoni, the causative agent for human schistosomiasis in the Western hemisphere. For the past two decades, tremendous advances have been made in research aimed at elucidating the molecular basis of the snail/parasite interaction. The growing concern that there is no vaccine to prevent schistosomiasis and only one effective drug in existence provides the impetus to develop new control strategies based on eliminating schistosomes at the snail-stage of the life cycle. To elucidate why a given snail is not always compatible to each and every schistosome it encounters, B. …

Microrna-21 Down-Regulates Rb1 Expression By Targeting Pdcd4 In Retinoblastoma, Fengmei Shen, Meng-Hsuan Mo, Shejuan An, Xiaohui Tan, Yebo Fu, M. Katayoon Rezaei, Zuoren Wang, Lin Zhang, Sidney W. Fu

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Retinoblastoma (RB) is a children’s ocular cancer caused by mutated retinoblastoma 1 (Rb1) gene on both alleles. Rb1 and other related genes could be regulated by microRNAs (miRNA) via complementarily pairing with their target sites. MicroRNA-21 (miR-21) possesses the oncogenic potential to target several tumor suppressor genes, including PDCD4, and regulates tumor progression and metastasis. However, the mechanism of how miR-21 regulates PDCD4 is poorly understood in RB. We investigated the expression of miRNAs in RB cell lines and identified that miR-21 is one of the most deregulated miRNAs in RB. Using qRT-PCR, we verified the expression level of several …

Schistosome And Liver Fluke Derived Catechol-Estrogens And Helminth Associated Cancers., José M. Correia Da Costa, Nuno Vale, Maria J. Gouveia, Mónica C. Botelho, Banchob Sripa, Lúcio L. Santos, Júlio H. Santos, Gabriel Rinaldi, Paul J. Brindley

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Infection with helminth parasites remains a persistent public health problem in developing countries. Three of these pathogens, the liver flukes Clonorchis sinensis, Opisthorchis viverrini and the blood fluke Schistosoma haematobium, are of particular concern due to their classification as Group 1 carcinogens: infection with these worms is carcinogenic. Using liquid chromatography-mass spectrometry (LC-MS/MS) approaches, we identified steroid hormone like (e.g., oxysterol-like, catechol estrogen quinone-like, etc.) metabolites and related DNA-adducts, apparently of parasite origin, in developmental stages including eggs of S. haematobium, in urine of people with urogenital schistosomiasis, and in the adult stage of O. viverrini. Since these kinds of …

Human Germline And Pan-Cancer Variomes And Their Distinct Functional Profiles, Yang Pan, Konstantinos Karagiannis, Haichen Zhang, Hayley Dingerdissen, Amirhossein Shamsaddini, Quan Wan, Vahan Simonyan, Raja Mazumder

Biochemistry and Molecular Medicine Faculty Publications

Identification of non-synonymous single nucleotide variations (nsSNVs) has exponentially increased due to advances in Next-Generation Sequencing technologies. The functional impacts of these variations have been difficult to ascertain because the corresponding knowledge about sequence functional sites is quite fragmented. It is clear that mapping of variations to sequence functional features can help us better understand the pathophysiological role of variations. In this study, we investigated the effect of nsSNVs on more than 17 common types of post-translational modification (PTM) sites, active sites and binding sites. Out of 1 705 285 distinct nsSNVs on 259 216 functional sites we identified 38 …

Fusion, 2014, George Washington University, William H. Beaumont Medical Research Honor Society

Fusion

No abstract provided.

Minor Gynecologic Surgery: A Review Of The Training Experience And Skill Building Opportunities For Providers In Low And Middle Income Countries, Rachel Marie Clark, Leslie Siriya Bradford, Jessica Opoku-Anane, Joseph Ngonzi, Ferdous Islam, Mithila Faruque, Annekathryn Goodman

Obstetrics and Gynecology Faculty Publications

Purpose: Minor gynecologic surgery is the cornerstone of gynecologic evaluation and intervention in countries with a well-established medical infrastructure. Surgical training and exposure to minor procedures are not available in low and middle-income countries due to the complex challenges of patient delay and lack of access to healthcare, physician shortages, and the lack of ancillary services such as pathology and radiology. This paper reviews current training statistics, the international literature on minor gynecologic surgery and training strategies.

Methods: PubMed searches using MESH terms cone biopsy, dilation and curettage, and loop electrosurgical excision procedure were performed. Statistics of minor …

Superresolution Imaging Of Human Cytomegalovirus Vmia Localization In Sub-Mitochondrial Compartments, Shivaprasad Bhuvanendran, Kyle Salka, Kristen Rainey, Sen Chandra Sreetama, Elizabeth Williams, Margretha Leeker, Vidhya Prasad, Jonathan Boyd, George H. Patterson, Jyoti K. Jaiswal, Anamaris M. Colberg-Poley

Pediatrics Faculty Publications

The human cytomegalovirus (HCMV) viral mitochondria-localized inhibitor of apoptosis (vMIA) protein, traffics to mitochondria-associated membranes (MAM), where the endoplasmic reticulum (ER) contacts the outer mitochondrial membrane (OMM). vMIA association with the MAM has not been visualized by imaging. Here, we have visualized this by using a combination of confocal and superresolution imaging. Deconvolution of confocal microscopy images shows vMIA localizes away from mitochondrial matrix at the Mitochondria-ER interface. By gated stimulated emission depletion (GSTED) imaging, we show that along this interface vMIA is distributed in clusters. Through multicolor, multifocal structured illumination microscopy (MSIM), we find vMIA clusters localize away from …

Perinatal Pharmacology, Karel M. Allegaert, V. Fanos, John N. Van Den Anker, Stephanie L. Läer

Pediatrics Faculty Publications

No abstract provided.

Preface Of The Special Issue: “Recent Cmv Research”, Kayla Dufrene, Roberta L. Debiasi, Anamaris M. Colberg-Poley

Pediatrics Faculty Publications

No abstract provided.

Expression Of A Secreted Fibroblast Growth Factor Binding Protein-1 (Fgfbp1) In Angioproliferative Kaposi Sarcoma, Patricio E. Ray, Ali Al-Attar, Xue-Hui Liu, Jharna R. Das, Elena Tassi, Anton Wellstein

Pediatrics Faculty Publications

Objective: Kaposi’s sarcoma (KS) is an angioproliferative disease frequently seen in patients with the acquired immunodeficiency syndrome (AIDS). Previous studies suggest that the HIV-1 protein Tat and Fibroblast Growth Factor 2 (FGF-2) have synergistic angiogenic effects in AIDS-KS tumors. However, the mechanisms by which FGF-2 is released and activated in KS tumors are not clearly defined. We carried out this study to determine whether an FGFbinding protein (FGFBP1 or BP1) that enhances the angiogenic activity of FGF-2 is expressed in AIDS-KS tumors, and to define whether BP1, FGF-2, and HIV-Tat protein-protein interactions could play a potential clinically role in the …

Immunologic Special Forces: Anti-Pathogen Cytotoxic T-Lymphocyte Immunotherapy Following Hematopoietic Stem Cell Transplantation, Michael Keller, Catherine M. Bollard

Pediatrics Faculty Publications

Anti-pathogen adoptive T-cell immunotherapy has been proven to be highly effective in preventing or controlling viral infections following hematopoietic stem cell transplantation. Recent advances in manufacturing protocols allow an increased number of targeted pathogens, eliminate the need for viral transduction, broaden the potential donor pool to include pathogen-naïve sources, and reduce the time requirement for production. Early studies suggest that anti-fungal immunotherapy may also have clinical benefit. Future advances include further broadening of the pathogens that can be targeted and development of T-cells with resistance to pharmacologic immunosuppression.

Strong Dna Deformation Required For Extremely Slow Dna Threading Intercalation By A Binuclear Ruthenium Complex, Ali A. Almaqwashi, Thayaparan Paramanathan, Per Lincoln, Ioulia Rouzina, Fredrik Westerlund, Mark C. Williams

Physics Faculty Publications

DNA intercalation by threading is expected to yield high affinity and slow dissociation, properties desirable for DNA-targeted therapeutics. To measure these properties, we utilize single molecule DNA stretching to quantify both the binding affinity and the force-dependent threading intercalation kinetics of the binuclear ruthenium complex Δ,Δ-[μ‐bidppz‐(phen)₄Ru₂]⁴⁺ (Δ,Δ-P). We measure the DNA elongation at a range of constant stretching forces using optical tweezers, allowing direct characterization of the intercalation kinetics as well as the amount intercalated at equilibrium. Higher forces exponentially facilitate the intercalative binding, leading to a profound decrease in the binding site size that …

Seasonal Patterns Of Microhabitat Selection By A Sub-Tropical Whip Spider, Phrynus Longipes, In The Luquillo Experimental Forest, Puerto Rico, Caroline A. Curtis, Christopher P. Bloch

Biological Sciences Faculty Publications

Phrynus longipes (Pocock 1894) is a top predator among arboreal invertebrates in the Luquillo Mountains of Puerto Rico, but many aspects of its ecology remain poorly understood. We sampled four of the most abundant tree species in the Luquillo Mountains during the dry and wet seasons of 2008 to evaluate microhabitat preferences of this species. In the dry season, P. longipes occurred significantly less frequently on a palm, Prestoea acuminata var. montana (Arecaceae), than the other tree species. Carapace length and the diameter of the tree on which an individual was found were positively correlated, suggesting competition for substrates. Microhabitat …

Avoidance Of Canopy Gaps By A Common Land Snail, Christopher P. Bloch, Michael Stock

Biological Sciences Faculty Publications

Because canopy gaps are characterized by elevated temperature and decreased humidity relative to closed-canopy forest, terrestrial gastropods may be exposed to greater desiccation stress in gaps than in undisturbed forest. We placed individuals of Caracolus caracolla at the edges of canopy gaps in montane forest in Puerto Rico and observed their movements. Individuals preferentially moved out of gaps except in one gap on the first night of the study, and the proportion of individuals recaptured inside gaps decreased over time. Individuals moved, on average, farther into forest than into gaps. Juveniles and adults responded similarly. These results suggest that C. …

Cognitive Impairment In Patients With Type 2 Diabetes Mellitus: Perspectives And Challenges, Okezie I. Aruoma, Darshini Narrain, Joseph Indelicato, Emmanuel Bourdon, Fatima Murad, Theeshan Bahorun

The School of Health Sciences Publications and Research

Type 2 Diabetes Mellitus is associated with elevated blood glucose level, abnormal abdominal fat deposition, insulin resistance and a number of complications including embryopathy, cardiovascular diseases, nephropathy, neuropathy, microangiopathy and retinopathy. Complications extending to the central nervous system may have a deteriorating effect on mental health including a decline in cognitive functioning. This could be a reason for depression, lack of compliance towards medication/treatment, and the inability of patients to meet the day-to-day management demands of the disease. Due to the high metabolic demand for energy in the brain, perturbations in glucose metabolism can noticeably impact cognitive performance. This review …

Front Matter

Journal of the Minnesota Academy of Science

No abstract provided.

Psychological Continuity: A Discussion Of Marc Slors' Account, Traumatic Experience, And The Significance Of Our Relations To Others, Pieranna Garavaso

Philosophy Publications

This paper addresses a question concerning psychological continuity, i.e., which features preserve the same psychological subject over time; this is not the same question as the one concerning the necessary and sufficient conditions for personal identity. Marc Slors (1998, 2001, 2001a) defends an account of psychological continuity that adds two features to Derek Parfit’s Relation R, namely narrativity and embodiment. Slors’ account is a significant improvement on Parfit’s, but still lacks an explicit acknowledgment of a third feature that I call relationality. Because they are usually regarded as cases of radical discontinuity, I start my discussion from the experiences of …

Development And Characterization Of Seven Polymorphic Microsatellite Loci In Bembidion Atrocaeruleum (Coleoptera: Carabidae), Matt J. O'Callaghan, Debra S. Finn, Mike Williams, Jonathan P. Sadler

College of Natural and Applied Sciences

We isolated seven polymorphic microsatellite loci from a ground beetle (Bembidion atrocaeruleum, Coleoptera, Carabidae (Stephens, 1826)) associated with naturally and regularly disturbed floodplain habitat in northwest Europe. Loci were tested on 157 individuals collected from five distinct habitat patches across two adjacent drainage basins in Wales, United Kingdom, to assess their potential for revealing population structure across a relatively short spatial extent. Alleles per locus ranged from 4 to 12. For a central representative population, expected heterozygosity ranged from 0.23 to 0.78 (mean: 0.63), and observed heterozygosity ranged from 0.16 to 0.94 (mean: 0.56). Analysis of molecular variance indicated significant …

Estimating Water Quality Effects Of Conservation Practices And Grazing Land Use Scenarios, Grace L. Wilson, Brent J. Dalzell, David J. Mulla, Toby Dogwiler, Paul M. Porter

College of Natural and Applied Sciences

Conservation management practices such as reduced tillage, fertilizer management, and buffer strips are well-established means by which to control erosion and nutrient losses from fields planted in annual row crops. However, agricultural systems which include perennial plant cover, such as the perennial forages found in grazing systems, may represent an alternative way to reduce these losses. In this study, management intensive rotational grazing (MIRG) was tested as a means by which to improve water quality on highly vulnerable row crop land, compared to more traditional conservation management schemes in the south branch of the Root River Watershed (a karst-influenced watershed …

Chemical And Biological Warfare: Teaching The Forbidden At A State University, David M. Claborn, Keith Payne

College of Health and Human Services

No abstract provided.

Development Of An Attribution Of Racial/Ethnic Health Disparities Scale, Robert E. Braun Phd., James H. Price, Jagdish Khubchandani, Erica Payton, Prasum Bhattacharjee

Health and Sport Sciences Faculty Scholarship

The purpose of this study was to develop an Attribution of Racial/Ethnic Health Disparities (AREHD) scale. A convenience sample of undergraduate college students (n = 423) at four Midwestern universities was recruited to respond to the survey. A pilot test with undergraduate students (n = 23) found the survey had good acceptability and readability level (SMOG = 11th grade). Using exploratory factor analysis we found the two a priori subscales were confirmed: individual responsibility and social determinants. Internal reliabilities of the subscales were: individual responsibility (alpha = 0.87) and social determinants (alpha = 0.90). Test–retest stability reliabilities were: individual responsibility …

Enhancing Ocean Research Data Access, Cyndy Chandler, Robert Groman, Adam Shepherd, Molly Allison, Robert Arko, Yu Chen, Peter Fox, David Glover, Pascal Hitzler, Adam Leadbetter, Thomas Narock, Patrick West, Peter Wiebe

Computer Science and Engineering Faculty Publications

No abstract provided.

Metabolic Suppression During Protracted Exposure To Hypoxia In The Jumbo Squid, Dosidicus Gigas, Living In An Oxygen Minimum Zone, Brad A. Seibel, N. Sören Häfker, Katja Trübenbach, Jing Zhang, Shannon N. Tessier, Hans-Otto Pörtner, Rui Rossa, Kenneth B. Storey

Biological Sciences Faculty Publications

The jumbo squid, Dosidicus gigas, can survive extended forays into the oxygen minimum zone (OMZ) of the Eastern Pacific Ocean. Previous studies have demonstrated reduced oxygen consumption and a limited anaerobic contribution to ATP production, suggesting the capacity for substantial metabolic suppression during hypoxic exposure. Here, we provide a more complete description of energy metabolism and explore the expression of proteins indicative of transcriptional and translational arrest that may contribute to metabolic suppression. We demonstrate a suppression of total ATP demand under hypoxic conditions (1% oxygen, P_O2=0.8 kPa) in both juveniles (52%) and adults (35%) of …

Icongraphy Of Torture: Going Beyond The Tortuous Torture Debate, Thomas W. Simon

Denver Journal of International Law & Policy

No abstract provided.

On (Not) Fearing The Mystery Of God (Chapter 8 Of The Spirit Of Adoption: Writers On Faith, Adoption, God, And More), Melanie Springer Mock

Faculty Publications - Department of English

Just days before our trip to India, birthplace of my second son, a well-meaning relative cornered me at a family gathering. "We'll be praying for you!" she said, uttering the Christian phrase that can be, at the same moment, both cliche-riddled and completely sincere.

I chose to interpret it as sincere, needing all kinds of prayer for our journey. My husband and I were flying to India with our then six-year-old sons: Benjamin, whom we'd adopted from Vietnam as an infant, and Samuel, whom we brought home from Mumbai as a three-year-old. This was no ordinary homeland trip. My adult …

People In Nature: Relational Discourse For Outdoor Educators, Thomas Beery

Research in Outdoor Education

Outdoor educators are concerned about a perceived human disconnection from nature. There is awareness of a lack of human affiliation, connection, or identity with nonhuman nature and its impact on attitudes and behaviors. This essay raises the possibility that despite our concern, we may contribute toward this disconnection via language that supports a separation of the natural and the cultural. Our ability to separate ourselves conceptually from the rest of nature may be partially to blame for environmental degradation, therefore challenging the nature-culture dichotomy is both useful and constructive. This essay will present examples of how outdoor educators can …