Raphael D. Isokpehi

Human Campylobacteriosis in Developing Countries1

Campylobacteriosis is a collective description for infectious diseases caused by members of the bacterial genus Campylobacter. The only form of campylobacteriosis of major public health importance is Campylobacter enteritis due to C. jejuni and C. coli. Research and control efforts on the disease have been conducted more often in developed countries than developing countries. However, because of the increasing incidence, expanding spectrum of infections, potential of HIV-related deaths due to Campylobacter, and the availability of the complete genome sequence of C. jejuni NCTC 11168, interest in campylobacteriosis research and control in developing countries is growing. We present the distinguishing epidemiologic and clinical features of Campylobacter enteritis in developing countries relative to developed countries. National surveillance programs and international collaborations are needed to address the substantial gaps in the knowledge about the epidemiology of campylobacteriosis in developing countries.

Identification of Drought-Responsive Universal Stress Proteins in Viridiplantae

Genes encoding proteins that contain the universal stress protein (USP) domain are known to provide bacteria, archaea, fungi, protozoa, and plants with the ability to respond to a plethora of environmental stresses. Specifically in plants, drought tolerance is a desirable phenotype. However, limited focused and organized functional genomic datasets exist on drought-responsive plant USP genes to facilitate their characterization. The overall objective of the investigation was to identify diverse plant universal stress proteins and Expressed Sequence Tags (ESTs) responsive to water-deficit stress. We hypothesize that cross-database mining of functional annotations in protein and gene transcript bioinformatics resources would help identify candidate drought-responsive universal stress proteins and transcripts from multiple plant species. Our bioinformatics approach retrieved, mined and integrated comprehensive functional annotation data on 511 protein and 1561 ESTs sequences from 161 viridiplantae taxa. A total of 32 drought-responsive ESTs from 7 plant genera Glycine, Hordeum, Manihot, Medicago, Oryza, Pinus and Triticum were identified. Two Arabidopsis USP genes At3g62550 and At3g53990 that encode ATP-binding motif were up-regulated in a drought microarray dataset. Further, a dataset of 80 simple sequence repeats (SSRs) linked to 20 singletons and 47 transcript assembles was constructed. Integrating the datasets on SSRs and drought-responsive ESTs identified three drought-responsive ESTs from bread wheat (BE604157), soybean (BM887317) and maritime pine (BX682209). The SSR sequence types were CAG, ATA and AT respectively. The datasets from cross-database mining provide organized resources for the characterization of USP genes as useful targets for engineering plant varieties tolerant to unfavorable environmental conditions.

The Case for Visual Analytics of Arsenic Concentrations in Foods

Arsenic is a naturally occurring toxic metal and its presence in food could be a potential risk to the health of both humans and animals. Prolonged ingestion of arsenic contaminated water may result in manifestations of toxicity in all systems of the body. Visual Analytics is a multidisciplinary field that is defined as the science of analytical reasoning facilitated by interactive visual interfaces. The concentrations of arsenic vary in foods making it impractical and impossible to provide regulatory limit for each food. This review article presents a case for the use of visual analytics approaches to provide comparative assessment of arsenic in various foods. The topics covered include (i) metabolism of arsenic in the human body; (ii) arsenic concentrations in various foods; (ii) factors affecting arsenic uptake in plants; (ii) introduction to visual analytics; and (iv) benefits of visual analytics for comparative assessment of arsenic concentration in foods. Visual analytics can provide an information superstructure of arsenic in various foods to permit insightful comparative risk assessment of the diverse and continually expanding data on arsenic in food groups in the context of country of study or origin, year of study, method of analysis and arsenic species.

Integrative sequence and tissue expression profiling of chicken and mammalian aquaporins

BackgroundProteins that selectively transport water across the membranes of cells are recognized as important in the normal functioning of the body systems of vertebrates. There are 13 known mammalian aquaporins (AQP0 to AQP12), some of which have been shown to have unexpected cellular roles beyond transmembrane water transport. The availability of non-mammalian vertebrate animal models has the potential to provide insight into the emergence of diverse function in the aquaporins. The domesticated chicken (Gallus gallus) is the premier avian model for biological research; however, only a limited number of studies have compared chicken and mammalian aquaporins. The identification of aquaporins that share functional motifs or are expressed in the same tissues in human and chicken could allow the further functional analyses of homologous aquaporins in both species. We hypothesize that integrative analyses of protein sequences and body site expression of human, mouse, rat and chicken aquaporins has the potential to yield novel biological hypotheses about the unexpected cellular roles of aquaporins beyond transmembrane water transport.ResultsA total of 76 aquaporin transcript models derived from 47 aquaporin genes were obtained for human, mouse, rat and chicken. Eleven body sites (brain, connective tissue, head, heart, liver, muscle, ovary, pancreas, small intestine, spleen and testis) were identified in which there is suggested expression of at least one mammalian and one chicken aquaporin. This study demonstrates that modern on-line analysis tools, a novel matrix integration technique, and the availability of the chicken genome for comparative genomics and expression analysis enables hypothesis generation in several important areas including: (i) alternative transcription and speciation effects on the conservation of functional motifs in vertebrate aquaporins; (ii) the emergence of basolateral targeting in mammalian species; (iii) the potential of the cysteine-rich AQP11 as a possible target in the pathophysiology of neurodegenerative disorders such as autism that involve Purkinje cells; and (iv) possible impairment of function of pancreas-expressed AQP12 during pancreatotropic necrosis in avian influenza virus infection.ConclusionThe investigation of aquaporin function in chicken and mammalian species has the potential to accelerate the discovery of novel knowledge of aquaporins in both avian and mammalian species.

Developmental Regulation of Genes encoding Universal stress proteins in Schistosoma mansoni

The draft nuclear genome sequence of the snail-transmitted, dimorphic, parasitic, platyhelminth Schistosoma mansoni revealed eight genes encoding proteins that contain the Universal Stress Protein (USP) domain. Schistosoma mansoni is a causative agent of human schistosomiasis, a severe and debilitating Neglected Tropical Disease (NTD) of poverty, which is endemic in at least 76 countries. The availability of the genome sequences of Schistosoma species presents opportunities for bioinformatics and genomics analyses of associated gene families that could be targets for understanding schistosomiasis ecology, intervention, prevention and control. Proteins with the USP domain are known to provide bacteria, archaea, fungi, protists and plants with the ability to respond to diverse environmental stresses. In this research investigation, the functional annotations of the USP genes and predicted nucleotide and protein sequences were initially verified. Subsequently, sequence clusters and distinctive features of the sequences were determined. A total of twelve ligand binding sites were predicted based on alignment to the ATP-binding universal stress protein from Methanocaldococcus jannaschii. In addition, six USP sequences showed the presence of ATP-binding motif residues indicating that they may be regulated by ATP. Public domain gene expression data and RT-PCR assays confirmed that all the S. mansoni USP genes were transcribed in at least one of the developmental life cycle stages of the helminth. Six of these genes were up-regulated in the miracidium, a free-swimming stage that is critical for transmission to the snail intermediate host. It is possible that during the intra-snail stages, S. mansoni gene transcripts for universal stress proteins are low abundant and are induced to perform specialized functions triggered by environmental stressors such as oxidative stress due to hydrogen peroxide that is present in the snail hemocytes. This report serves to catalyze the formation of a network of researchers to understand the function and regulation of the universal stress proteins encoded in genomes of schistosomes and their snail intermediate hosts.

Visual Analytics of Surveillance Data on Foodborne Vibriosis, United States, 1973–2010

Foodborne illnesses caused by microbial and chemical contaminants in food are a substantial health burden worldwide. In 2007, human vibriosis (non-cholera Vibrio infections) became a notifiable disease in the United States. In addition, Vibrio species are among the 31 major known pathogens transmitted through food in the United States. Diverse surveillance systems for foodborne pathogens also track outbreaks, illnesses, hospitalization and deaths due to non-cholera vibrios. Considering the recognition of vibriosis as a notifiable disease in the United States and the availability of diverse surveillance systems, there is a need for the development of easily deployed visualization and analysis approaches that can combine diverse data sources in an interactive manner. Current efforts to address this need are still limited. Visual analytics is an iterative process conducted via visual interfaces that involves collecting information, data preprocessing, knowledge representation, interaction, and decision making. We have utilized public domain outbreak and surveillance data sources covering 1973 to 2010, as well as visual analytics software to demonstrate integrated and interactive visualizations of data on foodborne outbreaks and surveillance of Vibrio species. Through the data visualization, we were able to identify unique patterns and/or novel relationships within and across datasets regarding (i) causative agent; (ii) foodborne outbreaks and illness per state; (iii) location of infection; (iv) vehicle (food) of infection; (v) anatomical site of isolation of Vibrio species; (vi) patients and complications of vibriosis; (vii) incidence of laboratory-confirmed vibriosis and V. parahaemolyticus outbreaks. The additional use of emerging visual analytics approaches for interaction with data on vibriosis, including non-foodborne related disease, can guide disease control and prevention as well as ongoing outbreak investigations.

The NIH National Center for Integrative Biomedical Informatics (NCIBI)

The National Center for Integrative and Biomedical Informatics (NCIBI) is one of the eight NCBCs. NCIBI supports information access and data analysis for biomedical researchers, enabling them to build computational and knowledge models of biological systems to address the Driving Biological Problems (DBPs). The NCIBI DBPs have included prostate cancer progression, organ-specific complications of type 1 and 2 diabetes, bipolar disorder, and metabolic analysis of obesity syndrome. Collaborating with these and other partners, NCIBI has developed a series of software tools for exploratory analysis, concept visualization, and literature searches, as well as core database and web services resources. Many of our training and outreach initiatives have been in collaboration with the Research Centers at Minority Institutions (RCMI), integrating NCIBI and RCMI faculty and students, culminating each year in an annual workshop. Our future directions include focusing on the TranSMART data sharing and analysis initiative.

Gas discharge visualization: an imaging and modeling tool for medical biometrics

The need for automated identification of a disease makes the issue of medical biometrics very current in our society. Not all biometric tools available provide real-time feedback. We introduce gas discharge visualization (GDV) technique as one of the biometric tools that have the potential to identify deviations from the normal functional state at early stages and in real time. GDV is a nonintrusive technique to capture the physiological and psychoemotional status of a person and the functional status of different organs and organ systems through the electrophotonic emissions of fingertips placed on the surface of an impulse analyzer. This paper first introduces biometrics and its different types and then specifically focuses on medical biometrics and the potential applications of GDV in medical biometrics. We also present our previous experience with GDV in the research regarding autism and the potential use of GDV in combination with computer science for the potential development of biological pattern/biomarker for different kinds of health abnormalities including cancer and mental diseases.

Aberrantly Expressed Genes in HaCaT Keratinocytes Chronically Exposed to Arsenic Trioxide

Inorganic arsenic is a known environmental toxicant and carcinogen of global public health concern. Arsenic is genotoxic and cytotoxic to human keratinocytes. However, the biological pathways perturbed in keratinocytes by low chronic dose inorganic arsenic are not completely understood. The objective of the investigation was to discover the mechanism of arsenic carcinogenicity in human epidermal keratinocytes. We hypothesize that a combined strategy of DNA microarray, qRT-PCR and gene function annotation will identify aberrantly expressed genes in HaCaT keratinocyte cell line after chronic treatment with arsenic trioxide. Microarray data analysis identified 14 up-regulated genes and 21 down-regulated genes in response to arsenic trioxide. The expression of 4 up-regulated genes and 1 down-regulated gene were confirmed by qRT-PCR. The up-regulated genes were AKR1C3 (Aldo-Keto Reductase family 1, member C3), IGFL1 (Insulin Growth Factor-Like family member 1), IL1R2 (Interleukin 1 Receptor, type 2), and TNFSF18 (Tumor Necrosis Factor [ligand] SuperFamily, member 18) and down-regulated gene was RGS2 (Regulator of G-protein Signaling 2). The observed over expression of TNFSF18 (167 fold) coupled with moderate expression of IGFL1 (3.1 fold), IL1R2 (5.9 fold) and AKR1C3 (9.2 fold) with a decreased RGS2 (2.0 fold) suggests that chronic arsenic exposure could produce sustained levels of TNF with modulation by an IL-1 analogue resulting in chronic immunologic insult. A concomitant decrease in growth inhibiting gene (RGS2) and increase in AKR1C3 may contribute to chronic inflammation leading to metaplasia, which may eventually lead to carcinogenicity in the skin keratinocytes. Also, increased expression of IGFL1 may trigger cancer development and progression in HaCaT keratinocytes.

Protozoan parasite aquaporins

Protozoan parasites are a major threat to human health with millions of fatalities worldwide, especially in nonindustrialized countries. Currently, there is no cure for many of these parasitic diseases. Consequently, there is an imperative to find treatment targets and develop novel drugs based on the proteins encoded in the genomes of these parasites. Aquaporins, members of membrane proteins discovered and characterized within the past 20 years, are the mechanism through which water is transported through living membranes. The presence of aquaporins explains disease etiology related to water physiology and presents new pharmacogenomic targets. In this article, we review the literature on aquaporins found in Apicomplexan, Kinetoplastida and Microsporidia parasites as potential drug targets. Furthermore, by analyzing protein motion dynamics, we identify impediments that need to be surmounted for developing effective drugs targeting the aquaglyceroporin of Plasmodium falciparum, the causative agent of the most fatal form of human malaria.