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Serum Bilirubin Concentration Is Modified By Ugt1a1 Haplotypes And Influences Risk Of Type-2 Diabetes In The Norfolk Island Genetic Isolate, M. C. Benton, R. A. Lea, D. Macartney-Coxson, C. Bellis, M. A. Carless, Joanne E. Curran, D. Eccles, G. K. Chambers, John Blangero, L. R. Griffiths

School of Medicine Publications and Presentations

Background

Located in the Pacific Ocean between Australia and New Zealand, the unique population isolate of Norfolk Island has been shown to exhibit increased prevalence of metabolic disorders (type-2 diabetes, cardiovascular disease) compared to mainland Australia. We investigated this well-established genetic isolate, utilising its unique genomic structure to increase the ability to detect related genetic markers. A pedigree-based genome-wide association study of 16 routinely collected blood-based clinical traits in 382 Norfolk Island individuals was performed.

Results

A striking association peak was located at chromosome 2q37.1 for both total bilirubin and direct bilirubin, with 29 SNPs reaching statistical significance (P …

Transcriptomics In Type 2 Diabetes: Bridging The Gap Between Genotype And Phenotype, Christopher Jenkinson, Harald H. H. Goring, Rector Arya, John Blangero, Ravindranath Duggirala, Ralph A. Defronzo

School of Medicine Publications and Presentations

Type 2 diabetes (T2D) is a common,multifactorial disease that is influenced by genetic and environmental factors and their interactions. However, common variants identified by genome wide association studies (GWAS) explain only about 10% of the total trait variance for T2D and less than 5% of the variance for obesity, indicating that a large proportion of heritability is still unexplained. The transcriptomic approach described here uses quantitative gene expression and disease-related physiological data (deep phenotyping) to measure the direct correlation between the expression of specific genes and physiological traits. Transcriptomic analysis bridges the gulf between GWAS and physiological studies. Recent GWAS …

Multi-Level Block Permutation, Anderson M. Winkler, Matthew A. Webster, Diego Vidaurre, Thomas E. Nichols, Stephen M. Smith

School of Medicine Publications and Presentations

Under weak and reasonable assumptions, mainly that data are exchangeable under the null hypothesis, permutation tests can provide exact control of false positives and allow the use of various non-standard statistics. There are, however, various common examples in which global exchangeability can be violated, including paired tests, tests that involve repeated measurements, tests in which subjects are relatives (members of pedigrees) - any dataset with known dependence among observations. In these cases, some permutations, if performed, would create data that would not possess the original dependence structure, and thus, should not be used to construct the reference (null) distribution. To …

Genome-Wide Significant Linkage Of Schizophrenia-Related Neuroanatomical Trait To 12q24, Emma Sprooten, Cota Navin Gupta, Emma Knowles, D. Reese Mckay, Samuel R. Mathias, Joanne E. Curran, Jack W. Kent Jr., Melanie A. Carless, Marcio Almeida, Thomas D. Dyer, Harald H. H. Goring, Rene L. Olvera, Peter T. Fox, Ravi Duggirala, Laura Almasy, John Blangero

School of Medicine Publications and Presentations

The insula and medial prefrontal cortex (mPFC) share functional, histological, transcriptional and developmental characteristics and they serve higher cognitive functions of theoretical relevance to schizophrenia and related disorders. Meta-analyses and multivariate analysis of structural magnetic resonance imaging (MRI) scans indicate that gray matter density and volume reductions in schizophrenia are the most consistent and pronounced in a network primarily composed of the insula and mPFC. We used source-based morphometry, a multivariate technique optimized for structural MRI, in a large sample of randomly ascertained pedigrees (N = 887) to derive an insula-mPFC component and to investigate its genetic determinants. Firstly, we …

Regulated Internalization Of Nmda Receptors Drives Pkd1-Mediated Suppression Of The Activity Of Residual Cell-Surface Nmda Receptors, Xiaoqian Fang, Haifa Qiao, Bradley R. Groveman, Shuang Feng, Melissa Pflueger, Wen-Kuan Xin, Mohammad K. Ali, Shuang-Xiu Lin, Jindong Xu, Florian Duclot, Mohamed Kabbaj, Wei Wang, Teresa Santiago-Sim

School of Medicine Publications and Presentations

Background

Constitutive and regulated internalization of cell surface proteins has been extensively investigated. The regulated internalization has been characterized as a principal mechanism for removing cell-surface receptors from the plasma membrane, and signaling to downstream targets of receptors. However, so far it is still not known whether the functional properties of remaining (non-internalized) receptor/channels may be regulated by internalization of the same class of receptor/channels. The N-methyl-D-aspartate receptor (NMDAR) is a principal subtype of glutamate-gated ion channel and plays key roles in neuronal plasticity and memory functions. NMDARs are well-known to undergo two types of regulated internalization – homologous and …

Long-Term Neural And Physiological Phenotyping Of A Single Human, Russell A. Poldrack, Timothy O. Laumann, Oluwasanmi Koyejo, Brenda Gregory, Ashleigh Hover, Mei-Yen Chen, Krzysztof J. Gorgolewski, Joanne E. Curran, Harald H. H. Goring, John Blangero

School of Medicine Publications and Presentations

Psychiatric disorders are characterized by major fluctuations in psychological function over the course of weeks and months, but the dynamic characteristics of brain function over this timescale in healthy individuals are unknown. Here, as a proof of concept to address this question, we present the MyConnectome project. An intensive phenome-wide assessment of a single human was performed over a period of 18 months, including functional and structural brain connectivity using magnetic resonance imaging, psychological function and physical health, gene expression and metabolomics. A reproducible analysis workflow is provided, along with open access to the data and an online browser for …

Impact Of Specialized Nursery Care For Late Preterm Infants On Nicu Admission Rate And Length Of Stay, Laura Hunt, Gene Hallford, Candace Robledo, Edgardo Szyld, Clara Song

School of Medicine Publications and Presentations

Objective To compare neonatal intensive care unit (NICU) admission rates and length of stay (LOS) of late preterm infants (LPIs) born before and after opening a specialized care nursery (SCN) at our academic, pediatric tertiary care center with 4,500 total deliveries annually

Study Design Retrospective chart review of inborn LPIs (350/7–366/7 weeks) who were asymptomatic or minimally symptomatic at birth and delivered 7 months before the opening of the SCN (pre-SCN) or 7 months subsequently (post-SCN). Infants were excluded for major congenital anomalies or other conditions requiring immediate NICU admission. The pre-SCN options for care were standard couplet care or …

A Global Perspective On The Influence Of Environmental Exposures On The Nervous System, Desire Tshala-Katumbay, Jean-Claude Mwanza, Diane S. Rohlman, Gladys E. Maestre, Reinaldo B. Oria

School of Medicine Publications and Presentations

Economic transitions in the era of globalization warrant a fresh look at the neurological risks associated with environmental change. These are driven by industrial expansion, transfer and mobility of goods, climate change and population growth. In these contexts, risk of infectious and non-infectious diseases are shared across geographical boundaries. In low- and middle-income countries, the risk of environmentally mediated brain disease is augmented several fold by lack of infrastructure, poor health and safety regulations, and limited measures for environmental protection. Neurological disorders may occur as a result of direct exposure to chemical and/or non-chemical stressors, including but not limited to, …

A Positive-Negative Mode Of Population Covariation Links Brain Connectivity, Demographics And Behavior, Stephen M. Smith, Thomas E. Nichols, Diego Vidaurre, Anderson M. Winkler, Timothy E J Behrens, Matthew F. Glasser, Kamil Ugurbil, Deanna M. Barch, David C. Van Essen, Karla L. Miller

School of Medicine Publications and Presentations

We investigated the relationship between individual subjects' functional connectomes and 280 behavioral and demographic measures in a single holistic multivariate analysis relating imaging to non-imaging data from 461 subjects in the Human Connectome Project. We identified one strong mode of population co-variation: subjects were predominantly spread along a single 'positive-negative' axis linking lifestyle, demographic and psychometric measures to each other and to a specific pattern of brain connectivity.

Cissus Quadrangularis Linn. Stem Ethanolic Extract Liberates Reactive Oxygen Species And Induces Mitochondria Mediated Apoptosis In Kb Cells, Saba Sheikh, Sahabjada Siddiqui, Anupam Dhasmana, Ejazul Haque, Mohammed Kamil, Mohtashim Lohani, Mohammad Arshad, Snober Shabnam Mir

School of Medicine Publications and Presentations

Background: Cissus quadrangularis Linn. (CQ) commonly known as Hadjod (Family: Vitaceae) is usually distributed in India and Sri Lanka and contains several bioactive compounds responsible for various metabolic and physiologic effects.

Objective: In this study, the biological effects of CQ ethanolic extract were evaluated by in vitro and supported by in silico analysis on KB oral epidermoid cancer cell line.

Materials and methods: Anti-cancer potential of ethanolic extract of CQ stem against KB oral epidermoid cancer cells was evaluated in terms of morphological analysis, nuclei staining, liberation of reactive oxygen species (ROS), cell cycle arrest, mitochondrial membrane potential (MMP) and …

Successes, Challenges And Needs Regarding Rural Health Medical Education In Continental Central America: A Literature Review And Narrative Synthesis, Maria C. Colon-Gonzalez, F. El Rayess, S. Guevara, G. Anandarajah

School of Medicine Publications and Presentations

Introduction: Central American countries, like many others, face a shortage of rural health physicians. Most medical schools in this region are located in urban areas and focus on tertiary care training rather than on community health or primary care, which are better suited for rural practice. However, many countries require young physicians to do community service in rural communities to address healthcare provider shortages. This study aimed to: (a) synthesize what is known about the current state of medical education preparing physicians for rural practice in this region, and (b) identify common needs, challenges and opportunities for improving medical education …

'Mutiny On The Bounty': The Genetic History Of Norfolk Island Reveals Extreme Gender-Biased Admixture, Miles C. Benton, Shani Stuart, Claire Bellis, Donia Macartney-Coxson, David Eccles, Joanne E. Curran, Geoff Chambers, John Blangero, Rod A. Lea, L. R. Griffiths

School of Medicine Publications and Presentations

Background

The Pacific Oceania region was one of the last regions of the world to be settled via human migration. Here we outline a settlement of this region that has given rise to a uniquely admixed population. The current Norfolk Island population has arisen from a small number of founders with mixed Caucasian and Polynesian ancestry, descendants of a famous historical event. The ‘Mutiny on the Bounty’ has been told in history books, songs and the big screen, but recently this story can be portrayed through comprehensive molecular genetics. Written history details betrayal and murder leading to the founding of …

Fatty Acids Linked To Cardiovascular Mortality Are Associated With Risk Factors, Sven O. E. Ebbesson, V. Saroja Voruganti, Paul B. Higgins, Richard R. Fabsitz, Lars O. Ebbesson, Sandra Laston, William S. Harris, John Kennish, Benjamin D. Umans, Hong Wang

School of Medicine Publications and Presentations

Background. Although saturated fatty acids (FAs) have been linked to cardiovascular mortality, it is not clear whether this outcome is attributable solely to their effects on low-density lipoprotein cholesterol (LDL-C) or whether other risk factors are also associated with FAs. The Western Alaskan Native population, with its rapidly changing lifestyles, shift in diet from unsaturated to saturated fatty acids and dramatic increase in cardiovascular disease (CVD), presents an opportunity to elucidate any associations between specific FAs and known CVD risk factors.

Objective. We tested the hypothesis that the specific FAs previously identified as related to CVD mortality are also associated …

Fast And Powerful Heritability Inference For Family-Based Neuroimaging Studies, Habib Ganjgahi, Anderson M. Winkler, David C. Glahn, John Blangero, Peter Kochunov, Thomas E. Nichols

School of Medicine Publications and Presentations

Heritability estimation has become an important tool for imaging genetics studies. The large number of voxel- and vertex-wise measurements in imaging genetics studies presents a challenge both in terms of computational intensity and the need to account for elevated false positive risk because of the multiple testing problem. There is a gap in existing tools, as standard neuroimaging software cannot estimate heritability, and yet standard quantitative genetics tools cannot provide essential neuroimaging inferences, like family-wise error corrected voxel-wise or cluster-wise P-values. Moreover, available heritability tools rely on P-values that can be inaccurate with usual parametric inference methods. In this work …

Alterations In Activation, Cytotoxic Capacity And Trafficking Profile Of Peripheral Cd8 T Cells In Young Adult Binge Drinkers, José Luis Zaldivar Fujigaki, América Guadalupe Arroyo Valerio, Juan Carlos Lopez Alvarenga, Esperanza Gabriela Gutiérrez Reyes, David Kershenobich, Joselin Hernández Ruiz

School of Medicine Publications and Presentations

Background: Excess of alcohol consumption is a public health problem and has documented effects on the immune system of humans and animals. Animal and in vitro studies suggest that alcohol abuse changes CD8 T cell (CD8) characteristics, however it remains unknown if the CD8 profile of binge drinkers is different in terms of activation, trafficking and cytotoxic capacity.

Aim: To analyze the peripheral CD8 cytotoxic capacity, activation and trafficking phenotypic profile of Mexican young adults with regard to alcohol consumption pattern.

Methods: 55 Mexican young adults were stratified as Light (20), Intermediate (18) or Binge drinkers (17) according to their …

Striatal Activity And Reduced White Matter Increase Frontal Activity In Youths With Family Histories Of Alcohol And Other Substance-Use Disorders Performing A Go/No-Go Task, Ashley Acheson, Malle A. Tagamets, Anderson M. Winkler, Laura M. Rowland, Charles W. Mathias, Susan N. Wright, L. Elliot Hong, Peter Kochunov, Donald M. Dougherty

School of Medicine Publications and Presentations

Introduction: Youths with a family history of alcohol and other drug use disorders (FH+) are at greater risk of developing substance-use disorders relative to those with no such family histories (FH-). We previously reported that FH+ youths have elevated activity in the supplementary motor area (SMA) and dorsal striatum while performing go/no-go tasks and have reduced frontal white matter integrity. A better understanding of relationships between these variables would provide insight into how frontostriatal circuitry is altered in FH+ youths, which may be an important contributor to their elevated risk.

Methods: In this study, we used structural equation modeling (SEM) …

In Silico Molecular Docking Analysis To Predict The Role Of Metal Ions In The Function Of Drug Targeted Proteins, S. M. A. Shahid, Qazi M. S. Jamal, J. M. Arif, Fahad M. Al-Khodairy, Anupam Dhasmana, Mohtashim Lohani

School of Medicine Publications and Presentations

Metal ions are required for many critical functions in living systems. Scarcity of some metal ions can lead to disease. A characteristic of metals is that they easily lose electrons from the familiar elemental or metallic state to form positively charged ions which tend to be soluble in biological fluids. Role of zinc, calcium and copper ions in the catalytic mechanism of drug targeted proteins such as Farnesyltransferase, Neuraminidase and Thioredoxin are analyzed using molecular docking, respectively. The docking results show that inhibitors have low Binding, docking and internal energies with proteins in the presence of Zn, Ca and Cu …

Anticancer Activity Of Cissus Quadrangularis: An In Vitro 2d Model Based Study, Saba Sheikh, Anupam Dhasmana, Sahabjada Siddiqui, Ejazul Haque

School of Medicine Publications and Presentations

Cissus quadrangularis (CQ) is a perennial rambling shrub of the grape family commonly known as “Hadjora” (in Hindi) probably native to India or Sri Lanka. It is one of the valuable medicines in the Indian Traditional Systems of Medicine because of the presence of several bioactive compounds. However, in the present study we have checked its anticancer activity along with its safety profile on normal skin cells. Apart from this we have generated the spheroid HeLa culture in vitro model for analyzing the CQ extract response on the growth of HeLa tumoroid. From the present findings we have observed that …

Does Maternal Asthma Contribute To Racial/Ethnic Disparities In Obstetric And Neonatal Complications?, Katrina F. Flores, Candace Robledo, Beom Seuk Hwang, Kira Leishear, Katherine Grantz, Pauline Mendola

School of Medicine Publications and Presentations

Purpose

Examine whether maternal asthma contributes to racial/ethnic differences in obstetric and neonatal complications.

Methods

Data on White (n=110,603), Black (n=50,284) and Hispanic (n=38,831) singleton deliveries came from the Consortium on Safe Labor. Multi-level logistic regression models, with an interaction term for asthma and race/ethnicity, estimated within-group adjusted odds ratios (aOR) for gestational diabetes, gestational hypertension, preeclampsia, placental abruption, premature rupture of membranes, preterm delivery, maternal hemorrhage, NICU admissions, small for gestational age (SGA), apnea, respiratory distress syndrome, transient tachypnea of the newborn, anemia and hyperbilirubinemia after adjustment for clinical and demographic confounders. Non-asthmatics of the same racial/ethnic group were …

Sequencing Strategies And Characterization Of 721 Vervet Monkey Genomes For Future Genetic Analyses Of Medically Relevant Traits, Yu S. Huang, Vasily Ramensky, Susan K. Service, Anna J. Jasinska, Yoon Jung, Oi-Wa Choi, Rita M. Cantor, Thomas D. Dyer, John Blangero

School of Medicine Publications and Presentations

Background

We report here the first genome-wide high-resolution polymorphism resource for non-human primate (NHP) association and linkage studies, constructed for the Caribbean-origin vervet monkey, or African green monkey (Chlorocebus aethiops sabaeus), one of the most widely used NHPs in biomedical research. We generated this resource by whole genome sequencing (WGS) of monkeys from the Vervet Research Colony (VRC), an NIH-supported research resource for which extensive phenotypic data are available.

Results

We identified genome-wide single nucleotide polymorphisms (SNPs) by WGS of 721 members of an extended pedigree from the VRC. From high-depth WGS data we identified more than 4 …

Heritability Of Fractional Anisotropy In Human White Matter: A Comparison Of Human Connectome Project And Enigma-Dti Data, Peter Kochunov, Neda Jahanshad, Daniel Marcus, Anderson M. Winkler, Laura Almasy, Joanne E. Curran, Ravi Duggirala, Peter T. Fox, Rene L. Olvera, John Blangero

School of Medicine Publications and Presentations

The degree to which genetic factors influence brain connectivity is beginning to be understood. Large-scale efforts are underway to map the profile of genetic effects in various brain regions. The NIH-funded Human Connectome Project (HCP) is providing data valuable for analyzing the degree of genetic influence underlying brain connectivity revealed by state-of-the-art neuroimaging methods. We calculated the heritability of the fractional anisotropy (FA) measure derived from diffusion tensor imaging (DTI) reconstruction in 481 HCP subjects (194/287 M/F) consisting of 57/60 pairs of mono- and dizygotic twins, and 246 siblings. FA measurements were derived using (Enhancing NeuroImaging Genetics through Meta-Analysis) ENIGMA …

Urinary Phthalate Metabolite Concentrations And Blood Glucose Levels During Pregnancy, Candace A. Robledo, Jennifer D. Peck, Julie A. Stoner, Antonia M. Calafat, Hélène Carabin, Linda Cowan, Jean R. Goodman

School of Medicine Publications and Presentations

Purpose: To examine associations between phthalate metabolite urinary concentrations during early pregnancy and blood glucose levels obtained at the time of screening for gestational diabetes mellitus (GDM).

Methods: Upon initiation of prenatal care, women with a mean gestational age of 12.8 weeks were recruited for a study of environmental chemical exposures (n = 110) and provided a spot urinary specimen. Blood glucose concentrations (mg/dl) were obtained from the electronic medical record for those patients who did not experience a pregnancy loss and did not transfer care to another facility prior to glucose screening (n = 72). Urinary concentrations of nine …

Common Genetic Variants Influence Human Subcortical Brain Structures, Derrek P. Hibar, Jason L. Stein, Miguel E. Renteria, Alejandro Arias-Vasquez, John Blangero, Anderson M. Winkler, Joanne E. Curran, Thomas D. Dyer, Peter T. Fox, Ravi Duggirala

School of Medicine Publications and Presentations

The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence …

Interaction Pattern For The Complex Of B-Dnafullerene Compounds With A Set Of Known Replication Proteins Using Docking Study, Sumbul Firdaus, Anupam Dhasmana, Vandana Srivastava, Tasneem Bano, Afreen Fatima, Qazi Mohammad Sajid Jamal, Roshan Jahan, Gulshan Wadhwad, Mohtashim Lohani

School of Medicine Publications and Presentations

Fullerenes have attracted considerable attention due to their unique chemical structure and potential applications which has opened wide venues for possible human exposure to various fullerene types. Therefore, in depth knowledge of how fullerene may interfere with various cellular processes becomes quite imperative. The present study was designed to investigate how the presence of fullerene affect the binding of DNA with different enzymes involved in replication process. Different fullerenes were first docked with DNA and then binding scores of different enzymes was analyzed with fullerene docked DNA. C30, C40 & C50 once docked with DNA, reduced the binding score of …

Association Of Insurance Status With Health Outcomes Following Traumatic Injury: Statewide Multicenter Analysis, Vatsal Chikani, Maureen Brophy, Anne Vossbrink, Khaleel Hussaini, Christopher Salvino, Jeffrey Skubic, Rogelio Martinez

School of Medicine Publications and Presentations

Introduction: Recognizing disparities in definitive care for traumatic injuries created by insurance status may help reduce the higher risk of trauma-related mortality in this population. Our objective was to understand the relationship between patients' insurance status and trauma outcomes.

Methods: We collected data on all patients involved in traumatic injury from eight Level I and 15 Level IV trauma centers, and four non-designated hospitals through Arizona State Trauma Registry between January 1, 2008 and December 31, 2011. Of 109,497 records queried, we excluded 29,062 (26.5%) due to missing data on primary payer, sex, race, zip code of residence, injury severity …

Interaction Pattern Of Fullerene Family With Different Forms Of Dna, Sumbul Firdaus, Mohtashim Lohani, Anupam Dhasmana, Mohd. Haneef

School of Medicine Publications and Presentations

Fullerenes have attracted considerable attention due to their unique chemical structure and potential applications. In this study fullerenes (C20 to C180) were interacted with different forms of DNA i.e. A, B and Z-forms. And no such change in the binding score was observed with the change in the sequence of DNA. In fact, binding score increases with the increase in the molecular weight of the fullerene while interacting with A & B-form of DNA but Z-form of DNA shows no regular pattern of binding. Number of interacting base pairs increases as the molecular size of fullerene increases. And the groove …

Genetic Influences On Response To Novel Objects And Dimensions Of Personality In Papio Baboons, Zachary Johnson, Linda Brent, Juan Carlos Lopez Alvarenga, Anthony G. Comuzzie, Wendy Shelledy, Stephanie Ramirez, Laura Cox, Michael C. Mahaney, Yung-Yu Huang, John Mann

School of Medicine Publications and Presentations

Behavioral variation within and between populations and species of the genus Papio has been studied extensively, but little is known about the genetic causes of individual- or population-level differences. This study investigates the influence of genetic variation on personality (sometimes referred to as temperament) in baboons and identifies a candidate gene partially responsible for the variation in that phenotype. To accomplish these goals, we examined individual variation in response to both novel objects and an apparent novel social partner (using a mirror test) among pedigreed baboons (n = 578) from the Southwest National Primate Research Center. We investigated the frequency …

Preconception And Early Pregnancy Air Pollution Exposures And Risk Of Gestational Diabetes Mellitus, Candace Robledo, Pauline Mendola, Edwina H. Yeung, Tuija Männistö, Rajeshwari Sundaram, Danping Liu, Qi Ying, Seth Sherman, Katherine Grantz

School of Medicine Publications and Presentations

Background: Air pollution has been linked to gestational diabetes mellitus (GDM) but no studies have evaluated impact of preconception and early pregnancy air pollution exposures on GDM risk.

Methods: Electronic medical records provided data on 219,952 singleton deliveries to mothers with (n=11,334) and without GDM (n=208,618). Average maternal exposures to particulate matter (PM) ≤ 2.5μm (PM2.5) and PM2.5 constituents, PM ≤ 10μm (PM10), nitrogen oxides (NOx), carbon monoxide, sulfur dioxide (SO2) and ozone (O3) were estimated for the 3-month preconception window, first trimester, and gestational weeks 1-24 based on modified Community Multiscale Air Quality models for delivery hospital referral regions. …

Disruption Of Skin Stem Cell Homeostasis Following Transplacental Arsenicosis; Alleviation By Combined Intake Of Selenium And Curcumin, Shiv Poojan, Sushil Kumar, Vikas Verma, Anupam Dhasmana, Mohtashim Lohani, Mukesh K. Verma

School of Medicine Publications and Presentations

Of late, a consirable interest has grown in literature on early development of arsenicosis and untimely death in humans after exposure to iAs in drinking water in utero or during the childhood. The mechanism of this kind of intrauterine arsenic poisoning is not known; however it is often suggested to involve stem cells. We looked into this possibility by investigating in mice the influence of chronic in utero exposure to arsenical drinking water preliminarily on multipotent adult stem cell and progenitor cell counts at the beginning of neonatal age. We found that repeated intake of 42.5 or 85ppm iAs in …

Binding Pattern Elucidation Of Nnk And Nnal Cigarette Smoke Carcinogens With Ner Pathway Enzymes: An Onco- Informatics Study, Qazi Mohammad Sajid Jamal, Anupam Dhasmana, Mohtashim Lohani, Sumbul Firdaus, Md Yousuf Ansari, Ganesh Chandra Sahoo, Shafiul Haque

School of Medicine Publications and Presentations

Cigarette smoke derivatives like NNK (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone) and NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butan-1-ol) are well-known carcinogens. We analyzed the interaction of enzymes involved in the NER (nucleotide excision repair) pathway with ligands (NNK and NNAL). Binding was characterized for the enzymes sharing equivalent or better interaction as compared to +Ve control. The highest obtained docking energy between NNK and enzymes RAD23A, CCNH, CDK7, and CETN2 were -7.13 kcal/mol, -7.27 kcal/mol, -8.05 kcal/mol and -7.58 kcal/mol respectively. Similarly the highest obtained docking energy between NNAL and enzymes RAD23A, CCNH, CDK7, and CETN2 were -7.46 kcal/mol, -7.94 kcal/mol, -7.83 kcal/mol and -7.67 kcal/mol respectively. In order …