Life Sciences Commons^™

Improved Genome-Scale Multitarget Virtual Screening Via A Novel Collaborative Filtering Approach To Cold-Start Problem, Hansaim Lim, Paul Gray, Lei Xie, Aleksandar Poleksic

Publications and Research

Conventional one-drug-one-gene approach has been of limited success in modern drug discovery. Polypharmacology, which focuses on searching for multi-targeted drugs to perturb disease-causing networks instead of designing selective ligands to target individual proteins, has emerged as a new drug discovery paradigm. Although many methods for single-target virtual screening have been developed to improve the efficiency of drug discovery, few of these algorithms are designed for polypharmacology. Here, we present a novel theoretical framework and a corresponding algorithm for genome-scale multitarget virtual screening based on the one-class collaborative filtering technique. Our method overcomes the sparseness of the protein-chemical interaction data by …

Striatal Dopaminergic Innervation Regulates Subthalamic Beta-Oscillations And Cortical-Subcortical Coupling During Movements: Preliminary Evidence In Subjects With Parkinson’S Disease, Andrea Canessa, Nicolo G. Pozzi, Gabriele Arnulfo, Joachim Brumberg, Martin M. Reich, Gianni Pezzoli, Maria F. Ghilardi, Cordula Matthies, Frank Steigerwald, Jens Volkman, Ioannis U. Isais

Publications and Research

Activation of the basal ganglia has been shown during the preparation and execution of movement. However, the functional interaction of cortical and subcortical brain areas during movement and the relative contribution of dopaminergic striatal innervation remains unclear. We recorded local field potential (LFP) activity from the subthalamic nucleus (STN) and high-density electroencephalography (EEG) signals in four patients with Parkinson’s disease (PD) off dopaminergic medication during a multi-joint motor task performed with their dominant and non-dominant hand. Recordings were performed by means of a fully-implantable deep brain stimulation (DBS) device at 4 months after surgery. Three patients also performed a single-photon …

Efficient Method For Transfer Of Microinjected Eggs To Mouse Ampulla For Generating Transgenic Mice, Guang Wen, Jin Di, Qian Li, Jianling Chen, Ling Jin, Cheng Wang, Sanqing Xu

Publications and Research

Background: The new method described here is highly efficient in transferring microinjected mouse eggs (MEs) through the bursa membrane of a surrogate mother mouse to the ampulla of the oviduct without damaging the blood vessels on the bursa membrane.

Results: This method causes no loss of blood, and it produces newborn pups/founders from approximately 70% of the transferred MEs, because only a small hole is made on the blood vessel–free area of the bursa membrane and ampulla of the surrogate mother mouse. The infundibulum remains intact. The small hole on the bursa membrane/ ampulla may already heal up before the …

Narrative Review Of Vitamin D And Its Specific Impact On Balance Capacity In Older Adults, Ray Marks

Publications and Research

Introduction and Aims: Falls injuries among older adults, a widespread well-established contributor to high disability levels, excess morbidity and mortality rates, have many causes. This review examines the association between vitamin D levels and postural stability or balance control—a fairly consistent predictor of falls among older adults.

Materials and Method: All relevant English language peer reviewed research publications detailing the relationship between vitamin D levels and balance control among the elderly were sought. Key words included “Vitamin D and Balance or Postural Control.” Databases used were Academic Search Complete, PubMed, Scopus, and Web of Science.

Results: Analysis showed no consistent …

Hiv Glycoprotein Gp120 Impairs Fast Axonal Transport By Activating Tak1 Signaling Pathways, Sarah H. Berth, Nichole Mesnard-Hoaglin, Bin Wang, Hajwa Kim, Yuyu Song, Maria Sapar, Gerardo Morfini, Scott T. Brady

Publications and Research

Sensory neuropathies are the most common neurological complication of HIV. Of these, distal sensory polyneuropathy (DSP) is directly caused by HIV infection and characterized by length-dependent axonal degeneration of dorsal root ganglion (DRG) neurons. Mechanisms for axonal degeneration in DSP remain unclear, but recent experiments revealed that the HIV glycoprotein gp120 is internalized and localized within axons of DRG neurons. Based on these findings, we investigated whether intra-axonal gp120 might impair fast axonal transport (FAT), a cellular process critical for appropriate maintenance of the axonal compartment. Significantly, we found that gp120 severely impaired both anterograde and retrograde FAT. Providing a …

Habitual Coffee Consumption And Risk Of Type 2 Diabetes, Ischemic Heart Disease, Depression And Alzheimer’S Disease: A Mendelian Randomization Study, Man Ki Kwok, Gabriel M. Leung, C. Mary Schooling

Publications and Research

Observationally, coffee is inversely associated with type 2 diabetes mellitus (T2DM), depression and Alzheimer’s disease, but not ischemic heart disease (IHD). Coffee features as possibly protective in the 2015 Dietary Guidelines for Americans. Short-term trials suggest coffee has neutral effect on most glycemic traits, but raises lipids and adiponectin. To clarify we compared T2DM, depression, Alzheimer’s disease, and IHD and its risk factors by genetically predicted coffee consumption using two-sample Mendelian randomization applied to large extensively genotyped case-control and cross-sectional studies. Childhood cognition was used as a negative control outcome. Genetically predicted coffee consumption was not associated with T2DM (odds …

Glucose-6-Phosphate Dehydrogenase Deficiency And Physical And Mental Health Until Adolescence, Man Ki Kwok, Gabriel M. Leung, C. Mary Schooling

Publications and Research

Background: To examine the association of glucose-6-phosphate dehydrogenase (G6PD) deficiency with adolescent physical and mental health, as effects of G6PD deficiency on health are rarely reported.

Methods: In a population-representative Chinese birth cohort: ªChildren of 1997º (n = 8,327), we estimated the adjusted associations of G6PD deficiency with growth using generalized estimating equations, with pubertal onset using interval censored regression, with hospitalization using Cox proportional hazards regression and with size, blood pressure, pubertal maturation and mental health using linear regression with multiple imputation and inverse probability weighting.

Results: Among 5,520 screened adolescents (66% follow-up), 4.8% boys and 0.5% girls had …

Improved Parental Dietary Quality Is Associated With Children’S Dietary Intake Through The Home Environment, Karen R. Flórez, A. S. Richardson, M. B. Ghosh-Dastidar, R. Beckman, C. Huang, L. Wagner, T. Dubowitz

Publications and Research

Background Improving access to supermarkets has been shown to improve some dietary outcomes, yet there is little evidence for such effects on children. Relatedly, there is a dearth of research assessing the impact of a structural change (i.e. supermarket in a former food desert) on the home environment and its relationship with children’s diet.

Objective Assess the relative impact of the home environment on children’s diet after the introduction of a new supermarket in a food desert.

Methods Among a randomly selected cohort of households living in a food desert, parental diet was assessed before and after the opening of …

Airborne Infectious Agents And Other Pollutants In Automobiles For Domestic Use: Potential Health Impacts And Approaches To Risk Mitigation, Syed A. Sattar, Kathryn E. Wright, Bahram Zargar, Joseph R. Rubino, M. Khalid Ijaz

Publications and Research

Theworld total of passenger cars is expected to go fromthe current one billion to >2.5 billion by 2050. Cars for domestic use account for ∼74% of the world’s yearly production ofmotorized vehicles. In North America, ∼80% of the commuters use their own car with another 5.6% travelling as passengers.With the current life-expectancy of 78.6 years, the average North American spends 4.3 years driving a car! This equates to driving 101 minutes/day with a lifetime driving distance of nearly 1.3 million km inside the confined and often shared space of the car with exposure to a mix of potentially harmful pathogens, …

Electro-Chemotactic Fields Induce Cooperative Movement Of Cns Cells, Shawn Mishra, Stephen Redenti, Maribel Vazquez

Publications and Research

Vision loss in adults with Age Related Macular Degeneration (AMD) is attributed to damage of retinal photoreceptor cells that initiate vision by absorbing light. Mouse models have suggested that transplantation of precursor cells may be a novel approach to restore vision. This project uses a combination of electrotactic and chemotactic stimuli to promote and guide CNS cell migration within a microdevice model.

Laboratory Exercises In Microbiology: Discovering The Unseen World Through Hands-On Investigation, Joan Petersen, Susan Mclaughlin

Open Educational Resources

The exercises in this laboratory manual are designed to engage students in hand-on activities that reinforce their understanding of the microbial world. Topics covered include: staining and microscopy, metabolic testing, physical and chemical control of microorganisms, and immunology. The target audience is primarily students preparing for a career in the health sciences, however many of the topics would be appropriate for a general microbiology course as well.

Implementing An Mhealth System For Substance Use Disorders In Primary Care: A Mixed Methods Study Of Clinicians’ Initial Expectations And First Year Experiences, Marie-Louise Mares, David H. Gustafson, Joseph E. Glass, Andrew Quanbeck, Helene Mcdowell, Fiona Mctavish, Amy K. Atwood, Lisa A. Marsch, Chanetelle Thomas, Dhavan Shah, Randall Brown, Andrew Isham, Mary Jane Nealon, Victoria Ward

Publications and Research

Background: Millions of Americans need but don’t receive treatment for substance use, and evidence suggests that addiction-focused interventions on smart phones could support their recovery. There is little research on implementation of addiction-related interventions in primary care, particularly in Federally Qualified Health Centers (FQHCs) that provide primary care to underserved populations. We used mixed methods to examine three FQHCs’ implementation of Seva, a smart-phone app that offers patients online support/discussion, health-tracking, and tools for coping with cravings, and offers clinicians information about patients’ health tracking and relapses. We examined (a) clinicians’ initial perspectives about implementing Seva, and (b) the first …

The Off-Label Use, Utility And Potential Value Of Tdcs In The Clinical Care Of Particular Neuropsychiatric Conditions, Marom Bikson, Bhaskar Paneri, James Giordano

Publications and Research

No abstract provided.

Insights Into The Molecular Roles Of Heparan Sulfate Proteoglycans (Hspgs-Syndecans) In Autocrine And Paracrine Growth Factor Signaling In The Pathogenesis Of Hodgkin's Lymphoma, Rajendra Ghardbaran

Publications and Research

Syndecans (SDC, SYND) comprise a group of four structurally related type 1 transmembrane heparan sulfate proteoglycans (HSPGs) that play important roles in tumorigenic processes. SDCs exert signaling via their protein cores and their conserved transmembrane and cytoplasmic domains or by forming complexes with growth factors (GFs). In classical Hodgkin's lymphoma (cHL), a lymphoid neoplasm of predominantly B cell origin, SDC1 and SDC4 are the active SDCs, and a number of GF (vascular endothelial growth factor, fibroblast growth factor, etc.) signaling pathways have been studied. However, despite extensive pre-clinical and clinical research on SDC-mediated GF signaling in many cancer types, there …

Synthetic And Biological Exploration Of (+)-Boldine - Identification Of Potential Cns Receptor Ligands, Sujay Joseph

Theses and Dissertations

(+)-Boldine, an aporphine alkaloid, is reported to be biologically active at various Central Nervous System(CNS) receptors. However, only a few Structure Activity Relationship(SAR) studies have been conducted using boldine’s aporphine scaffold. A library of novel analogs was synthesized from boldine to understand the effect of bisbenzylation at C2 and C9 positions on the affinity and selectivity at the serotonin receptors.

Anomaly Detection In Host Signaling Pathways For The Early Prognosis Of Acute Infection, Kun Wang, Stanley Langevin, Corey S. O'Hern, Mark D. Shattuck, Serenity Ogle, Adriana Forero, Juliet Morrison, Richard Slayden, Michael G. Katze, Michael Kirby

Publications and Research

Clinical diagnosis of acute infectious diseases during the early stages of infection is critical to administering the appropriate treatment to improve the disease outcome. We present a data driven analysis of the human cellular response to respiratory viruses including influenza, respiratory syncytia virus, and human rhinovirus, and compared this with the response to the bacterial endotoxin, Lipopolysaccharides (LPS). Using an anomaly detection framework we identified pathways that clearly distinguish between asymptomatic and symptomatic patients infected with the four different respiratory viruses and that accurately diagnosed patients exposed to a bacterial infection. Connectivity pathway analysis comparing the viral and bacterial diagnostic …

Prophylactic Bacteriophage Administration More Effective Than Post-Infection Administration In Reducing Salmonella Enterica Serovar Enteritidis Shedding In Quail, Mosab Ahmadi, M. Amir Karimi Torshizi, Shaban Rahimi, John J. Dennehy

Publications and Research

Infections caused by Salmonella bacteria, often through poultry products, are a serious public health issue. Because of drawbacks associated with antibiotic prophylaxis, alternative treatments are sought. Bacterial viruses (bacteriophages) may provide an effective alternative, but concerns remain with respect to bacteriophage stability and effectiveness. To this end, we assessed the stability of a novel bacteriophage isolated from poultry excreta, siphovirus PSE, and its effectiveness in reducing Salmonella enterica serovar Enteritidis colonization in vitro and in vivo. Moreover, we sought to determine how the timing (prophylactic or therapeutic) and route (oral gavage or vent lip) of PSE administration impacted its effectiveness. …

Biodiversity Of Medicinal Plants In The Highlands: Problems And Perspectives, Vyacheslav Dushenkov

Publications and Research

Climate change is affecting medicinal plants around the world and could ultimately lead to losses of some key species, in particular species endemic to a region and causing plants to migrate to new ranges. As the situation unfolds, climate change may become a pressing issue for the herbal community, affecting medicinal plant supply chains with varying requirements for plant cultivation, resource management in the wild, harvesting, processing, and importantly marketing.

Tricurin, A Novel Formulation Of Curcumin, Epicatechin Gallate, And Resveratrol, Inhibits The Tumorigenicity Of Human Papillomaviruspositive Head And Neck Squamous Cell Carcinoma, Longzhu Piao, Sumit Mukherjee, Qing Chang, Xiujie Xie, Hong Li, Mario R. Castellanos, Probal Banerjee, Hassan Iqbal, Ryan Ivancic, Xueqian Wang, Theodoros N. Teknos, Quintin Pan

Publications and Research

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide with about 600,000 new cases diagnosed in the last year. The incidence of human papillomavirus-positive head and neck squamous cell carcinoma (HPV-positive HNSCC) has rapidly increased over the past 30 years prompting the suggestion that an epidemic may be on the horizon. Therefore, there is a clinical need to develop alternate therapeutic strategies to manage the growing number of HPV-positive HNSCC patients. TriCurin is a composition of three food-derived polyphenols in unique stoichiometric proportions consisting of curcumin from the spice turmeric, resveratrol from red grapes, and …

Botanical Therapeutics In The Modern World, Vyacheslav Dushenkov, Brittany L. Graf, Mary Ann Lila

Publications and Research

Plants are the source of a broad spectrum of biologically active phytochemicals. For effective defense against pathogens and abiotic stress, plants have developed complicated chemical strategies with different mechanisms of action. By harnessing these phytochemicals, humans have used plants for medicinal purposes for over 30,000 years, and they remain a valuable source for the development of modern therapeutics. Plant-derived materials are utilized as pharmaceuticals, botanical drugs, dietary supplements (nutraceuticals), functional food ingredients, and cosmeceuticals. The Global Institute for Bioexploration (GIBEX), an international conglomerate of researchers, is involved in multiple botanical therapeutics discovery and development programs.

Reliability Of Clinical Evaluators Of Spasticity In Patients With Stroke, Tiffany Alvino, Shiney David, Chelsea Gendvil

Dissertations, Theses, and Capstone Projects

Spasticity is characterized by hyperexcitable stretch reflexes with amplitude increases in response to velocity dependent passive movement and resistance. Spasticity is the result of abnormal function of segmental and suprasegmental neuronal circuits. The objective of this study was to determine any positive correlation between three clinical evaluators of spasticity (i.e., the pendulum test, the patellar tendon tap test (PTT), and the Modified Ashworth scale) in their reliability to assess spasticity in people post-stroke. It was hypothesized that the use of force movement sensors along with surface electromyography increases the reliability of the standardized clinical tests. The results show that all …

Transition Issues In Educational Audiology, Rebecca Bareli

Dissertations, Theses, and Capstone Projects

Despite advancements in assistive technology for hearing loss (hearing aids, cochlear implants), children with hearing loss still face a host of issues throughout the educational process, particularly during transitional periods. This literature review examines the existing research discussing these issues, including transitions from childhood to adolescence, high school to college, and college to the workforce.

Neuroanatomical Alterations In High-Functioning Adults With Autism Spectrum Disorder, Tehila Eilam-Stock, Tingting Wu, Alfredo Spagna, Laura J. Egan, Jin Fan

Publications and Research

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental condition, affecting cognition and behavior throughout the life span. With recent advances in neuroimaging techniques and analytical approaches, a considerable effort has been directed toward identifying the neuroanatomical underpinnings of ASD. While gray-matter abnormalities have been found throughout cortical, subcortical, and cerebellar regions of affected individuals, there is currently little consistency across findings, partly due to small sample-sizes and great heterogeneity among participants in previous studies. Here, we report voxel-based morphometry of structural magnetic resonance images in a relatively large sample of high-functioning adults with ASD (n = 66) and matched …

Mechanism Of Action And Applications Of Interleukin 24 In Immunotherapy, Leah Persaud, Dayenny De Jesus, Oliver Brannigan, Maria Richiez-Paredes, Jeannette Huaman, Giselle Alvarado, Linda Riker, Gissete Mendez, Jordan Dejoie, Moira Sauane

Publications and Research

Interleukin 24 (IL-24) is an important pleiotropic immunoregulatory cytokine, whose gene is located in human chromosome 1q32-33. IL-24’s signaling pathways have diverse biological functions related to cell differentiation, proliferation, development, apoptosis, and inflammation, placing it at the center of an active area of research. IL-24 is well known for its apoptotic effect in cancer cells while having no such effect on normal cells. IL-24 can also be secreted by both immune and non-immune cells. Downstream effects of IL-24, after binding to the IL-20 receptor, can occur dependently or independently of the JAK/STAT signal transduction pathway, which is classically involved in …

Epigenetic Profiles Signify Cell Fate Plasticity In Unipotent Spermatogonial Stem And Progenitor Cells, Ying Liu, Eugenia G. Giannopoulou, Duacheng Wen, Ilaria Falciatori, Oliver Elemento, C. David Allis, Shahin Rafii, Marco Seandel

Publications and Research

Spermatogonial stem and progenitor cells (SSCs) generate adult male gametes. During in vitro expansion, these unipotent murine cells spontaneously convert to multipotent adult spermatogonial-derived stem cells (MASCs). Here we investigate this conversion process through integrative transcriptomic and epigenomic analyses. We find in SSCs that promoters essential to maintenance and differentiation of embryonic stem cells (ESCs) are enriched with histone H3-lysine4 and -lysine 27 trimethylations. These bivalent modifications are maintained at most somatic promoters after conversion, bestowing MASCs an ESC-like promoter chromatin. At enhancers, the core pluripotency circuitry is activated partially in SSCs and completely in MASCs, concomitant with loss of …

From Mollusks To Medicine: A Venomics Approach For The Discovery And Characterization Of Therapeutics From Terebridae Peptide Toxins, Aida Verdes, Prachi Anand, Juliette Gorson, Stephen Jannetti, Patrick Kelly, Abba Leffler, Danny Simpson, Girish Ramrattan, Mandë Holford

Publications and Research

Animal venoms comprise a diversity of peptide toxins that manipulate molecular targets such as ion channels and receptors, making venom peptides attractive candidates for the development of therapeutics to benefit human health. However, identifying bioactive venom peptides remains a significant challenge. In this review we describe our particular venomics strategy for the discovery, characterization, and optimization of Terebridae venom peptides, teretoxins. Our strategy reflects the scientific path from mollusks to medicine in an integrative sequential approach with the following steps: (1) delimitation of venomous Terebridae lineages through taxonomic and phylogenetic analyses; (2) identification and classification of putative teretoxins through omics …

Comparative Error-Free And Error-Prone Translesion Synthesis Of N2‑2′-Deoxyguanosine Adducts Formed By Mitomycin C And Its Metabolite, 2,7-Diaminomitosene, In Human Cells, Arindam Bose, Chaitra Surugihalli, Paritosh Pande, Elise Champeil, Ashis K. Basu

Publications and Research

Mitomycin C (MC) is a cytotoxic and mutagenic antitumor agent that alkylates DNA upon reductive activation. 2,7-Diaminomitosene (2,7-DAM) is a major metabolite of MC in tumor cells, which also alkylates DNA. MC forms seven DNA adducts, including monoadducts and inter- and intrastrand cross-links, whereas 2,7-DAM forms two monoadducts. Herein, the biological effects of the dG-N2 adducts formed by MC and 2,7-DAM have been compared by constructing single-stranded plasmids containing these adducts and replicating them in human embryonic kidney 293T cells. Translesion synthesis (TLS) efficiencies of dG-N2-MC and dG-N2-2,7-DAM were 38 ± 3 and 27 …

Inquiry Into The Implementation Of Bush’S Executive Order 13211 And The Impact On Environmental And Public Health Regulation, Elizabeth Ann Glass Geltman, Gunwant Gill, Miriam Jovanovic

Publications and Research

Executive Order 13211, promulgated in 2001, requires the federal government to consider the impact of federal action on energy independence as part of the George W. Bush’s National Energy Policy. This law review examines whether EO 13211 was used to curtail environmental protection and natural resource conservation. The article begins with a review of the procedure required of federal agencies under EO 13211 and its associated documents. The paper then examines case law and published federal rulemaking proceedings and examines how federal agencies apply tests to evaluate the potential energy effect. The study concludes that EO 13211 strikes a reasonable …

A Model Of Blood Pressure, Heart Rate, And Vaso-Vagal Responses Produced By Vestibulo-Sympathetic Activation, Theodore Raphan, Bernard Cohen, Yongqing Xiang, Sergei B. Yakushin

Publications and Research

Blood Pressure (BP), comprised of recurrent systoles and diastoles, is controlled by central mechanisms to maintain blood flow. Periodic behavior of BP was modeled to study how peak amplitudes and frequencies of the systoles are modulated by vestibular activation. The model was implemented as a relaxation oscillator, driven by a central signal related to Desired BP. Relaxation oscillations were maintained by a second order system comprising two integrators and a threshold element in the feedback loop. The output signal related to BP was generated as a nonlinear function of the derivative of the first state variable, which is a summation …

Abnormal Tau Induces Cognitive Impairment Through Two Different Mechanisms: Synaptic Dysfunction And Neuronal Loss, J. Di, L. S. Cohen, C. P. Corbo, Greg R. Phillips, Abdeslem El Idrissi, Alejandra D. Alonso

Publications and Research

The hyperphosphorylated microtubule-associated protein tau is present in several neurodegenerative diseases, although the causal relationship remains elusive. Few mouse models used to study Alzheimerlike dementia target tau phosphorylation. We created an inducible pseudophosphorylated tau (Pathological Human Tau, PH-Tau) mouse model to study the effect of conformationally modified tau in vivo. Leaky expression resulted in two levels of PH-Tau: low basal level and higher upon induction (4% and 14% of the endogenous tau, respectively). Unexpectedly, low PH-Tau resulted in significant cognitive deficits, decrease in the number of synapses (seen by EM in the CA1 region), reduction of synaptic proteins, and localization …