Pharmacology, Toxicology and Environmental Health Commons^™

Competition Between Ski And Creb-Binding Protein For Binding To Smad Proteins In Transforming Growth Factor-Beta Signaling, Weijun Chen, Suvana Lam, Hema Srinath, Celia Schiffer, William Royer, Kai Lin

Celia A. Schiffer

The family of Smad proteins mediates transforming growth factor-beta (TGF-beta) signaling in cell growth and differentiation. Smads repress or activate TGF-beta signaling by interacting with corepressors (e.g. Ski) or coactivators (e.g. CREB-binding protein (CBP)), respectively. Specifically, Ski has been shown to interfere with the interaction between Smad3 and CBP. However, it is unclear whether Ski competes with CBP for binding to Smads and whether they can interact with Smad3 at the same binding surface on Smad3. We investigated the interactions among purified constructs of Smad, Ski, and CBP in vitro by size-exclusion chromatography, isothermal titration calorimetry, and mutational studies. Here, …

Mass Spectrometry Analysis Of Hiv-1 Vif Reveals An Increase In Ordered Structure Upon Oligomerization In Regions Necessary For Viral Infectivity, Jared Auclair, Karin Green, Shivender Shandilya, James Evans, Mohan Somasundaran, Celia Schiffer

Celia A. Schiffer

HIV-1 Vif, an accessory protein in the viral genome, performs an important role in viral pathogenesis by facilitating the degradation of APOBEC3G, an endogenous cellular inhibitor of HIV-1 replication. In this study, intrinsically disordered regions are predicted in HIV-1 Vif using sequence-based algorithms. Intrinsic disorder may explain why traditional structure determination of HIV-1 Vif has been elusive, making structure-based drug design impossible. To characterize HIV-1 Vif's structural topology and to map the domains involved in oligomerization we used chemical cross-linking, proteolysis, and mass spectrometry. Cross-linking showed evidence of monomer, dimer, and trimer species via denaturing gel analysis and an additional …

Exploring The Role Of The Solvent In The Denaturation Of A Protein: A Molecular Dynamics Study Of The Dna Binding Domain Of The 434 Repressor, Celia Schiffer, Volker Dötsch, Kurt Wuthrich, Wilfred Van Gunsteren

Celia A. Schiffer

Molecular dynamics simulations of the DNA binding domain of 434 repressor are presented which aim at unraveling the role of solvent in protein denaturation. Four altered solvent models, each mimicking various possible aspects of the addition of a denaturant to the aqueous solvent, were used in the simulations to analyze their effects on the stability of the protein. The solvent was altered by selectively changing the Coulombic interaction between water and protein atoms and between different water molecules. The use of a modified solvent model has the advantage of mimicking the presence of denaturant without having denaturant molecules present in …

Structural Analysis Of Human Immunodeficiency Virus Type 1 Crf01_Ae Protease In Complex With The Substrate P1-P6., Rajintha Bandaranayake, Moses Prabu-Jeyabalan, Junko Kakizawa, Wataru Sugiura, Celia Schiffer

Celia A. Schiffer

The effect of amino acid variability between human immunodeficiency virus type 1 (HIV-1) clades on structure and the emergence of resistance mutations in HIV-1 protease has become an area of significant interest in recent years. We determined the first crystal structure of the HIV-1 CRF01_AE protease in complex with the p1-p6 substrate to a resolution of 2.8 A. Hydrogen bonding between the flap hinge and the protease core regions shows significant structural rearrangements in CRF01_AE protease compared to the clade B protease structure.

Non-Viral Enos Gene Delivery And Transfection With Stents For The Treatment Of Restenosis, Luis A. Brito, Saradha Chandrasekhar, Steven R. Little, Mansoor M. Amiji

Mansoor M. Amiji

Background In this study, we have examined local non-viral gene delivery, transfection, and therapeutic efficacy of endothelial nitric oxide synthase (eNOS) encoding plasmid DNA administered using coated stents in a rabbit iliac artery restenosis model. Methods Lipopolyplexes (LPPs) with eNOS expressing plasmid DNA were immobilized on stainless steel stents using poly(D,L-lactide-co-glycolide) (PLGA) and type B gelatin coatings. The gene-eluting stents were implanted bilaterally in the denuded iliac arteries and eNOS transfection and therapeutic efficacy were examined 14 days after implantation. Results The results show that non-viral lipopolyplex-coated stents can efficiently tranfect eNOS locally in the arterial lumen assessed by PCR …

Phasic Activity Of Urinary Bladder Smooth Muscle In The Streptozotocin-Induced Diabetic Rat: Effect Of Potassium Channel Modulators, Bahareh Vahabi, Kim Lawson, Neil G. Mckay, Donna Sellers

Donna Sellers

Increased phasic activity in the bladder smooth muscle of animal models and patients with detrusor overactivity has been suggested to underlie the pathophysiology of overactive bladder. Potassium (K+) channels are key regulators of bladder smooth muscle tone and thus may play a role in this altered phasic activity. In this study the effects of K+ channel modulators on the phasic activity of bladder strips from the streptozotocin-induced diabetic rat model of bladder dysfunction were investigated. Bladder strips from rats 1 week following streptozotocin administration and age-matched controls were mounted in tissue baths at 37 °C and the effects of K+ …

The Growth Suppressing Effects Of Girinimbine On Hepg2 Involve Induction Of Apoptosis And Cell Cycle Arrest, Syam Mohan

Syam Mohan

Murraya koenigii is an edible herb widely used in folk medicine. Here we report that girinimbine, a carbazole alkaloid isolated from this plant, inhibited the growth and induced apoptosis in human hepatocellular carcinoma, HepG2 cells. The MTT and LDH assay results showed that girinimbine decreased cell viability and increased cytotoxicity in a dose-and time-dependent manner selectively. Girinimbine-treated HepG2 cells showed typical morphological features of apoptosis, as observed from normal inverted microscopy and Hoechst 33342 assay. Furthermore, girinimbine treatment resulted in DNA fragmentation and elevated levels of caspase-3 in HepG2 cells. Girinimbine treatment also displayed a time-dependent accumulation of the Sub-G(0)/G(1) …

Assessment Of Organic And Inorganic Phosphorus In Soils Derived From Cretaceous Sediments And Basement Complex Soils Of Guinea Savannah Of Kogi State, North Central Nigeria, Sunday I. Amhakhian, H H. Isitekhale, Charles I. Oyewole

Confluence Journal Environmental Studies (CJES), Kogi State University, Nigeria

A pot experiment was carried out using 20 surface soils (0-15cm depth) in 2008 to assess soil organic phosphorus and some fraction of inorganic phosphorus in other to know their availability in the soils of the studied area and also work have not been done in this areas in respect to organic and in-organic phosphorus. The experiment was conducted using 20 soils 10 from each geological formation (Cretaceous sediments and Basement complex soils), respectively. The mean organic phosphorus of 63.51 mgkg 1 soil was obtained for Cretaceous sediment soils and 158.54 mgkg 1 soil for the basement complex soils respectively. …

Development Of Functional Indices Of Facility Occurrence Towards The Distribution Of Social Services In Lagos Island Nigeria., Augustus O. Atubi

Confluence Journal Environmental Studies (CJES), Kogi State University, Nigeria

Proper coordination of transport and public facilities provision is vital to any balanced regional development strategy. The central aim of this study, therefore, is to find out what the relationship is between access to the transport network and the provision of functional indices of facility occurrence towards the distribution of social services in Lagos Island, Nigeria. In particular it seeks to find out areas that have below or above average level of facility occurrences relative to the level of accessibility. However, a pair wise correlation matrix of the eleven (11) variables employed in the index construction was carried out. The …

Urban Climate And Challenges Of Tropical Cities, B E. Omogbai

Confluence Journal Environmental Studies (CJES), Kogi State University, Nigeria

This study examines the nature of urban climate, features and the challenges on the developing tropical cities in the 21st century. It argues that the use of principles of urban climate would help in providing comfortable living conditions and problem immune working environments for the inhabitants of tropical cities. The findings reveal that owing to poor environmental planning, inadequate geotechnical landscape surveys prior to the development of urban infrastructures, and non-adherence to the principles of urban climate, challenges of landscape degradation, excessive flooding of the built infrastructures, heat-island effects, and collapse of buildings have emerged. Suggested measures to avert these …

Detecting Changes In Landuse/Cover Of Umuahia, South-Eastern Nigeria Using Remote Sensing And Gis Techniques, Fanan Ujoh, Olarewaju Oluseyi Ifatimehin, Adams Ndalai Baba

Confluence Journal Environmental Studies (CJES), Kogi State University, Nigeria

Since 1991 when it became the capital city of Abia State, Umuahia has undergone tremendous transformation in its land use and land cover due to rapid urbanization. The main materials employed for this study are a land use map (1991) and Landsat ETM+satellite image (2007) of the study area. These, combined with field survey/checks, were brought into a GIS environment using ILWIS 3.2 Academic image classification software to map the land use/land cover and to estimate the rate of urban expansion and loss of rural land at the peri-urban fringes of Umuahia between 1991 and 2007. The study revealed significant …

Gender Participation In The Management Of Tricycle Transport For Youth Empowerment And Sustainable Development In Kano State, Nigeria, Nuratu Muhammed

Confluence Journal Environmental Studies (CJES), Kogi State University, Nigeria

The research examined gender participation in the management of tricycle for youth empowerment and sustainable development in Kano state, Nigeria. Stratified random sampling technique was used to select samples of drivers(150), passengers (150) and owners/managers the female tricycle owners fell under this category and they numbered(65).All together a total of 365 samples were selected for the study. Data obtained from the primary data was analyzed using simple statistical techniques and chi square test to ascertain whether there was any significant differences in some of the variables tested. The results of the analysis revealed that the main difference was found in …

Environmental Problems Of Industrialization And Sustainable Development In Nigeria - A Review, Adejoh Iyaji

Confluence Journal Environmental Studies (CJES), Kogi State University, Nigeria

The main objective of this paper is to examine the impact of the quest for industrialization on the environment in Nigeria; others include, the identification of the objectives of sustainable development as well as making recommendations that will lead to the much needed sustainable environment both for the present generation and generations yet unborn. The researcher relied principally on secondary sources of data for this paper which is theoretical in approach. Findings revealed the emergence of a host of environmental problems such as air pollution, deforestation, desertification, solid and hazardous waste problems in the wake of the quest for industrialization. …

Eschar-Associated Spotted Fever Rickettsiosis, Bahia, Brazil, Nanci Silva, Marina Eremeeva, Tatiana Rozental, Guilherme S. Ribeiro, Christopher D. Paddock, Eduardo Antonio G. Ramos, Alexsandra R.M. Favacho, Mitermayer G. Reis, Gregory A. Dasch,, Elba R.S. De Lemos, Albert I. Ko

Marina E. Eremeeva

In Brazil, Brazilian spotted fever was once considered the only tick-borne rickettsial disease. We report eschar-associated rickettsial disease that occurred after a tick bite. The etiologic agent is most related to Rickettsia parkeri, R. africae, and R. sibirica and probably widely distributed from São Paulo to Bahia in the Atlantic Forest.

Comparison Of Renal Effects Of Ibuprofen Versus Indomethacin During Treatment Of Patent Ductus Arteriosus In Contiguous Historical Cohorts, Alla Kushnir, Joaquim Mb Pinheiro

Alla Kushnir

No abstract provided.

Spatial Distribution Of Commercial Banks In Ilorin Metropolis, Kwara State, Nigeria, I B. Abdullahi, M A. Ijaiya, A Abdulraheem, R I. Abdulkadir, R O. Ibrahim

Confluence Journal of Environmental Studies (CJES), Kogi State University, Nigeria

The spatial distribution of banks in any geographic entity determines the level of accessibility to its services by the public. This study examined the pattern of banks distribution in Ilorin metropolis. Field survey was employed in determining the number of available commercial banks and their respective distances between each other. The spatial analysis technique such as the nearest neighbour analysis as used ascertain the degree of clustering, density and the average distance taken to access these services. The study revealed that about 96% of the total number of banks are situated in the Central Business District which exhibited a very …

Emergence Of A Novel Human Ehrlichia-Muris Like Organism In North America – Wisconsin And Minnesota, Bobbi S. Pritt, Lynne M. Sloan, Diep K. Hoang-Johnson, Ulrike G. Munderloh, Susan M. Paskewitz, Kristina M. Mcelroy, Jevon D. Mcfadden, Matthew J. Binnicker, David F. Neitzel, Gongping Liu, William L. Nicholson, Curtis M. Nelson, Joni J. Franson, Scott A. Martin, Scott A. Cunningham, Christopher R. Steward, Kay Bogumill, Mary E. Bjorgaard, Jeffrey P. Davis, Jennifer H. Mcquiston, David M. Warshauer, Mark P. Wilhelm, Robin Patel, Vipul A. Trivedi, Marina Eremeeva

Marina E. Eremeeva

Background: Ehrlichiosis is a clinically important, emerging zoonosis. Only Ehrlichia chaffeensis and E. ewingii have been thought to cause ehrlichiosis in humans in the United States. Patients with suspected ehrlichiosis routinely undergo testing to ensure proper diagnosis and to ascertain the cause.

Methods: We used molecular methods, culturing, and serologic testing to diagnose and ascertain the cause of cases of ehrlichiosis.

Results: On testing, four cases of ehrlichiosis in Minnesota or Wisconsin were found not to be from E. chaffeensis or E. ewingii and instead to be caused by a newly discovered ehrlichia species.

All patients had fever, …

Adaptive Responses To Flooding Incidents In Ilorin, Kwara State, Nigeria, Habiba I. Jimoh, Kayode A. Iroye

Confluence Journal Environmental Studies (CJES), Kogi State University, Nigeria

Incidents of floods which are mainly caused by changes in landuse is fast becoming a city life experience in Ilorin as in most urban centres in Nigeria causing untold hardships and sometimes loss of lives. This extreme hydro-meteorological event is also being exacerbated by climate change which thus calls for adaptive response by residents towards reducing its risks, hence this study. Data used were generated from direct field measurements and questionnaire administration. Descriptive statistics and cross tabulations were used in analyzing the data. Results obtained indicate that most respondents use a wide range of non-structural adaptive response to flood. The …

An Assessment Of Socio-Economic Impact Of Waste Scavenging As A Means Of Poverty Alleviation In Gwagwalada, Abuja., John Yakubu Magaji, Samuel Panse Dakyes

Confluence Journal Environmental Studies (CJES), Kogi State University, Nigeria

Waste scavengers are usually perceived as being among the poor, and scavenging is considered a marginal activity. They tend to have low incomes, but can obtained decent earning when they are not exploited by middlemen. This study was conducted in Gwagwalada town with the aim of assessing the socio-economic impact of scavenging on the people. A structured questionnaire was constructed to capture the demographic characteristics of the scavengers, their experiences, types of items scavenged, the economic gains and the challenges being faced. The target pollution is waste scavengers and a random sampling technique was adopted in selecting the respondents for …

Rocky Mountain Spotted Fever In Panama: A Cluster Description, Maribel Tribaldos, Yamitzel Zaldivar, Sergio Bermudez, Franklyn Samudio, Yaxelis Mendoza, Alexander A. Martinez, Rodrigo Villalobos, Marina Eremeeva, Christopher D. Paddock, Kathleen Page, Rebecca E. Smith, Juan Miguel Pascale

Marina E. Eremeeva

Rocky Mountain spotted fever (RMSF) is a tick-borne infection caused by Rickettsia rickettsii. We report a cluster of fatal cases of RMSF in 2007 in Panama, involving a pregnant woman and two children from the same family. The woman presented with a fever followed by respiratory distress, maculopapular rash, and an eschar at the site from which a tick had been removed. She died four days after disease onset. This is the second published report of an eschar in a patient confirmed by PCR to be infected with R. rickettsii. One month later, the children presented within days of one …