Life Sciences Commons^™

Translating Genetic And Preclinical Findings Into Autism Therapies, Maria Chahrour, Robin Kleiman, M Chiara Manzini

Pharmacology and Physiology Faculty Publications

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social deficits and repetitive/restrictive interests. ASD is associated with multiple comorbidities, including intellectual disability, anxiety, and epilepsy. Evidence that ASD is highly heritable has spurred major efforts to unravel its genetics, revealing possible contributions from hundreds of genes through rare and common variation and through copy-number changes. In this perspective, we provide an overview of the current state of ASD genetics and of how genetic research has spurred the development of in vivo and in vitro models using animals and patient cells to evaluate the impact of genetic mutations …

Superresolution Imaging Identifies That Conventional Trafficking Pathways Are Not Essential For Endoplasmic Reticulum To Outer Mitochondrial Membrane Protein Transport., Kyle Salka, Shivaprasad Bhuvanendran, Kassandra Wilson, Petros Bozidis, Mansi Mehta, Kristin Rainey, Hiromi Sesaki, George H Patterson, Jyoti K. Jaiswal, Anamaris M. Colberg-Poley

Genomics and Precision Medicine Faculty Publications

Most nuclear-encoded mitochondrial proteins traffic from the cytosol to mitochondria. Some of these proteins localize at mitochondria-associated membranes (MAM), where mitochondria are closely apposed with the endoplasmic reticulum (ER). We have previously shown that the human cytomegalovirus signal-anchored protein known as viral mitochondria-localized inhibitor of apoptosis (vMIA) traffics from the ER to mitochondria and clusters at the outer mitochondrial membrane (OMM). Here, we have examined the host pathways by which vMIA traffics from the ER to mitochondria and clusters at the OMM. By disruption of phosphofurin acidic cluster sorting protein 2 (PACS-2), mitofusins (Mfn1/2), and dynamin related protein 1 (Drp1), …

24-Month Hiv-Free Survival Among Infants Born To Hiv-Positive Women Enrolled In Option B+ Program In Kigali, Rwanda: The Kabeho Study, Michelle Gill, Heather J. Hoffman, Dieudonne Ndatimana, Placidie Mugwaneza, Laura Guay, +Several Additional Authors

Genomics and Precision Medicine Faculty Publications

Lifelong antiretroviral therapy (ART) provision to all pregnant HIV-positive women (“Option B+”) has been recommended by the World Health Organization since 2013, but there remain limited data on the effects of Option B+ on long-term HIV-free survival in breastfeeding HIV-exposed infants. The Kigali Antiretroviral and Breastfeeding Assessment for the Elimination of HIV (Kabeho) study enrolled HIV-positive women from the third trimester of pregnancy to 2 weeks postpartum in 14 heath facilities implementing Option B+ in Kigali, Rwanda. Mother–child pairs in the longitudinal observational cohort were followed until 24 months postpartum, with HIV diagnostic testing at 6 weeks, and 9, 18 …

Plasma Fibroblast Growth Factor-21 Levels In Patients With Inborn Errors Of Metabolism, Brian Kirmse, Juan Cabrera-Luque, Omar Ayyub, Kristina Cusmano-Ozog, Kimberly A. Chapman, Marshall L. Summar

Pediatrics Faculty Publications

Fibroblast growth factor-21 (FGF21) levels are elevated in patients with primary mitochondrial disorders but have not been studied in patients with inborn errors of metabolism (IEM) known to have secondary mitochondrial dysfunction. We measured plasma FGF21 by ELISA in patients with and without IEM. FGF21 levels were higher in patients with IEM compared to without IEM (370 pg/dL vs. 0–65 pg/dL). Further study of FGF21 as a biomarker in IEM is warranted.

Robust Expression Of Tumor Suppressor Mirna's Let-7 And Mir-195 Detected In Plasma Of Saudi Female Breast Cancer Patients., Amal Qattan, Haya Intabli, Wafa Alkhayal, Chafica Eltabache, Taher Tweigieri, Suad Bin Amer

Biochemistry and Molecular Medicine Faculty Publications

Background

Female breast cancer is frequently diagnosed at a later stage and the leading cause of cancer deaths world-wide. Levels of cell-free circulating microRNAs (miRNAs) can potentially be used as biomarkers to measure disease progression in breast cancer patients in a non-invasive way and are therefore of high clinical value.

Methods

Using quantitative RT-PCR, circulating miRNAs were measured in blood samples collected from disease-free individuals (n = 34), triple-negative breast tumours (TNBC) (n = 36) and luminal tumours (n = 57). In addition to intergroup comparisons, plasma miRNA expression levels of all groups were analyzed against RNASeq …

Cardiovascular Health Is Associated With Physical Function Among Older Community Dwelling Men And Women., Yichen Jin, Toshiko Tanaka, Yan Ma, Stefania Bandinelli, Luigi Ferrucci, Sameera A Talegawkar

Exercise and Nutrition Sciences Faculty Publications

Background

Age related decline in physical function is a significant concern affecting the quality of life of older individuals.

Methods

We examined the associations between baseline overall cardiovascular health (CVH), its components, and physical function in 906 men and women from the InCHIANTI cohort. Physical function was assessed using the Short Performance Physical Battery and poor physical function was defined as an Short Performance Physical Battery score less than 10. Overall CVH score, ranging from 0 to 12 in the cohort, was operationalized using adherence to ideal levels for health behaviors including smoking status, physical activity, body mass index, and …

An Organismal Model For Gene Regulatory Networks In The Gut-Associated Immune Response, Katherine M. Buckley, J P. Rast

Biochemistry and Molecular Medicine Faculty Publications

The gut epithelium is an ancient site of complex communication between the animal immune system and the microbial world. While elements of self-non-self receptors and effector mechanisms differ greatly among animal phyla, some aspects of recognition, regulation, and response are broadly conserved. A gene regulatory network (GRN) approach provides a means to investigate the nature of this conservation and divergence even as more peripheral functional details remain incompletely understood. The sea urchin embryo is an unparalleled experimental model for detangling the GRNs that govern embryonic development. By applying this theoretical framework to the free swimming, feeding larval stage of the …

Myoblasts And Macrophages Are Required For Therapeutic Morpholino Antisense Oligonucleotide Delivery To Dystrophic Muscle., James S Novak, Marshall W Hogarth, Jessica F Boehler, Marie Nearing, Maria C Vila, Raul Heredia, Alyson A Fiorillo, Aiping Zhang, Yetrib Hathout, Eric P Hoffman, Jyoti K Jaiswal, Kanneboyina Nagaraju, Sebahattin Cirak, Terence A Partridge

Pediatrics Faculty Publications

Exon skipping is a promising therapeutic strategy for Duchenne muscular dystrophy (DMD), employing morpholino antisense oligonucleotides (PMO-AO) to exclude disruptive exons from the mutant DMD transcript and elicit production of truncated dystrophin protein. Clinical trials for PMO show variable and sporadic dystrophin rescue. Here, we show that robust PMO uptake and efficient production of dystrophin following PMO administration coincide with areas of myofiber regeneration and inflammation. PMO localization is sustained in inflammatory foci where it enters macrophages, actively differentiating myoblasts and newly forming myotubes. We conclude that efficient PMO delivery into muscle requires two concomitant events: first, accumulation and retention …

Phylogenetic Evidence From Freshwater Crayfishes That Cave Adaptation Is Not An Evolutionary Dead-End., David B Stern, Jesse Breinholt, Carlos Pedraza-Lara, Marilú López-Mejía, Christopher L Owen, Heather Bracken-Grissom, James W Fetzner, Keith A Crandall

Computational Biology Institute

Caves are perceived as isolated, extreme habitats with a uniquely specialized biota, which long ago led to the idea that caves are "evolutionary dead-ends." This implies that cave-adapted taxa may be doomed for extinction before they can diversify or transition to a more stable state. However, this hypothesis has not been explicitly tested in a phylogenetic framework with multiple independently evolved cave-dwelling groups. Here, we use the freshwater crayfish, a group with dozens of cave-dwelling species in multiple lineages, as a system to test this hypothesis. We consider historical patterns of lineage diversification and habitat transition as well as current …

T-Cell Responses Targeting Hiv Nef Uniquely Correlate With Infected Cell Frequencies After Long-Term Antiretroviral Therapy., Allison S Thomas, Kimberley L Jones, Rajesh T Gandhi, Deborah K Mcmahon, Joshua C Cyktor, Dora Chan, Szu-Han Huang, Ronald Truong, Alberto Bosque, Amanda B Macedo, Colin Kovacs, Erika Benko, Joseph J Eron, Ronald J Bosch, Christina M Lalama, Samuel Simmens, Bruce D Walker, John W Mellors, R Brad Jones

Microbiology, Immunology, and Tropical Medicine Faculty Publications

HIV-specific CD8+ T-cell responses limit viral replication in untreated infection. After the initiation of antiretroviral therapy (ART), these responses decay and the infected cell population that remains is commonly considered to be invisible to T-cells. We hypothesized that HIV antigen recognition may persist in ART-treated individuals due to low-level or episodic protein expression. We posited that if persistent recognition were occurring it would be preferentially directed against the early HIV gene products Nef, Tat, and Rev as compared to late gene products, such as Gag, Pol, and Env, which have higher barriers to expression. Using a primary cell model of …

Leukocyte Telomere Length, T Cell Composition And Dna Methylation Age., Brian H Chen, Cara L Carty, Masayuki Kimura, Jeremy D Kark, Wei Chen, Shengxu Li, Tao Zhang, Charles Kooperberg, Daniel Levy, Themistocles Assimes, Devin Absher, Steve Horvath, Alexander P Reiner, Abraham Aviv

Clinical Research and Leadership Faculty Publications

Both leukocyte telomere length (LTL) and DNA methylation age are strongly associated with chronological age. One measure of DNA methylation age-the extrinsic epigenetic age acceleration (EEAA)-is highly predictive of all-cause mortality. We examined the relation between LTL and EEAA. LTL was measured by Southern blots and leukocyte DNA methylation was determined using Illumina Infinium HumanMethylation450 BeadChip in participants in the Women's Health Initiative (WHI; n=804), the Framingham Heart Study (FHS; n=909) and the Bogalusa Heart study (BHS; n=826). EEAA was computed using 71 DNA methylation sites, further weighted by proportions of naïve CD8+ T cells, memory CD8+ T cells, and …

Alcohol, Stem Cells And Cancer., Shoujun Gu, Bao-Ngoc Nguyen, Shuyun Rao, Shulin Li, Kirti Shetty, Asif Rashid, Vivek Shukla, Chu-Xia Deng, Lopa Mishra, Bibhuti Mishra

Surgery Faculty Publications

Dosage, gender, and genetic susceptibility to the effects of alcohol remained only partially elucidated. In this review, we summarize the current knowledge of the mechanisms underlying the role of alcohol in liver and gastrointestinal cancers. In addition, two recent pathways- DNA repair and TGF-β signaling which provide new insights into alcohol in the regulation of cancers and stem cells are also discussed here.

Temporal Changes In Cortical And Hippocampal Expression Of Genes Important For Brain Glucose Metabolism Following Controlled Cortical Impact Injury In Mice, June Zhou, Mark Burns, Linda Huynh, Sonia Villapol, Daniel D. Taub, Juan M. Saavedra, Marc R. Blackman

Pharmacology and Physiology Faculty Publications

Traumatic brain injury (TBI) causes transient increases and subsequent decreases in brain glucose utilization. The underlying molecular pathways are orchestrated processes and poorly understood. In the current study, we determined temporal changes in cortical and hippocampal expression of genes important for brain glucose/lactate metabolism and the effect of a known neuroprotective drug telmisartan on the expression of these genes after experimental TBI. Adult male C57BL/6J mice (n = 6/group) underwent sham or unilateral controlled cortical impact (CCI) injury. Their ipsilateral and contralateral cortex and hippocampus were collected 6 h, 1, 3, 7, 14, 21, and 28 days after injury. …

The Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism Rs4340 Associates With Habitual Physical Activity Among European American Adults., Michael Bruneau, Theodore J Angelopoulos, Paul Gordon, Niall Moyna, Paul Visich, Robert Zoeller, Rick Seip, Stephen Bilbie, Paul Thompson, Joseph Devaney, Heather Gordish-Dressman, Eric Hoffman, Linda S Pescatello

Genomics and Precision Medicine Faculty Publications

BACKGROUND: The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism (rs4340) (ACE DIP) accounts for half of the variability in plasma ACE concentrations. ACE has been widely studied for its influence on sports performance; however, research on its influence in physical activity is limited and inconsistent. We examined the influence of the ACE DIP on physical activity among 461 European Americans.

METHODS: Subjects completed the Paffenbarger Physical Activity Questionnaire for weekly walking distance. Multivariate analysis of covariance (MANCOVA) tested log-transformed differences in weekly walking distance among ACE DIP genotypes (II, ID, DD) with gender as a fixed factor, and age and body …

Anti-Herv-K (Hml-2) Capsid Antibody Responses In Hiv Elite Controllers., Miguel De Mulder, Devi Sengupta, Steven G Deeks, Jeffrey N Martin, Christopher D Pilcher, Frederick M Hecht, Jonah B Sacha, Douglas F Nixon, Henri-Alexandre Michaud

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome and while the majority are transcriptionally silent, the most recently integrated HERV, HERV-K (HML-2), remains active. During HIV infection, HERV-K (HML-2) specific mRNA transcripts and viral proteins can be detected. In this study, we aimed to understand the antibody response against HERV-K (HML-2) Gag in the context of HIV-1 infection.

Results

We developed an ELISA assay using either recombinant protein or 164 redundant “15mer” HERV-K (HML-2) Gag peptides to test sera for antibody reactivity. We identified a total of eight potential HERV-K (HML-2) Gag immunogenic domains: two on …

Engaging Medical Students In Problem-Based Search And Study Of The Biomedical Literature., Zhiyong Han, Samantha L Margulies, Divya Kurian, Joshua M Jabaut, Akshita Mehta, Ramzi Dudum, Huberta Koudoro, Ria S Roberts, Jay Lee, Jonathan Li, Hieu T Nguyen, Mark Elliott

Biochemistry and Molecular Medicine Faculty Publications

No abstract provided.

Metastasis-Associated Protein 1 Deficiency Results In Compromised Pulmonary Alveolar Capillary Angiogenesis In Mice., Jun-Hui Qin, Zhen-Yu Ke, Qiang Zhou, Li Wang, Yuan Liang, Ying-Mei Wang, Tong Yang, Xing Gao, Jing Ye, Rekesh Kumar, Rui-An Wang

Biochemistry and Molecular Medicine Faculty Publications

Background

The aim of this study was to investigate the effects of metastasis-associated protein 1 (MTA1) deficiency during angiogenesis of pulmonary alveolar capillaries in mice and to determine the molecular mechanisms involved.

Material/Methods

The expressions of MTA1, CD34, vascular endothelial growth factor (VEGF), alpha smooth muscle actin (α-SMA), and HIF-1α were analyzed in the lungs of MTA1-knockout (KO) and wild-type mice at embryonic day 18.5 and 2 months by quantitative PCR, immunoblotting, and immunohistochemistry. The morphological changes were investigated during pulmonary alveolar capillary formation. The heart weight/body weight (HW/BW) ratio and the size of the right ventricular wall cardiomyocytes …

Overexpressed Somatic Alleles Are Enriched In Functional Elements In Breast Cancer., Paula Restrepo, Mercedeh Movassagh, Nawaf Alomran, Christian Miller, Muzi Li, Chris Trenkov, Yulian Manchev, Sonali Bahl, Stephanie Warnken, Liam Spurr, Tatiyana Apanasovich, Keith Crandall, Nathan Edwards, Anelia Horvath

Pharmacology and Physiology Faculty Publications

Asymmetric allele content in the transcriptome can be indicative of functional and selective features of the underlying genetic variants. Yet, imbalanced alleles, especially from diploid genome regions, are poorly explored in cancer. Here we systematically quantify and integrate the variant allele fraction from corresponding RNA and DNA sequence data from patients with breast cancer acquired through The Cancer Genome Atlas (TCGA). We test for correlation between allele prevalence and functionality in known cancer-implicated genes from the Cancer Gene Census (CGC). We document significant allele-preferential expression of functional variants in CGC genes and across the entire dataset. Notably, we find frequent …

Cardio-Metabolic Benefits Of Plant-Based Diets., Hana Kahleova, Susan Levin, Neal Barnard

Medicine Faculty Publications

Cardio-metabolic disease, namely ischemic heart disease, stroke, obesity, and type 2 diabetes, represent substantial health and economic burdens. Almost one half of cardio-metabolic deaths in the U.S. might be prevented through proper nutrition. Plant-based (vegetarian and vegan) diets are an effective strategy for improving nutrient intake. At the same time, they are associated with decreased all-cause mortality and decreased risk of obesity, type 2 diabetes, and coronary heart disease. Evidence suggests that plant-based diets may reduce the risk of coronary heart disease events by an estimated 40% and the risk of cerebral vascular disease events by 29%. These diets also …

Increased Expression Of The Tight Junction Protein Tjp1/Zo-1 Is Associated With Upregulation Of Taz-Tead Activity And An Adult Tissue Stem Cell Signature In Carfilzomib-Resistant Multiple Myeloma Cells And High-Risk Multiple Myeloma Patients, Irene Riz, Robert G. Hawley

Anatomy and Regenerative Biology Faculty Publications

Tight junction protein 1 (TJP1) has recently been proposed as a biomarker to identify multiple myeloma (MM) patients most likely to respond to bortezomiband carfilzomib-based proteasome inhibitor regimens. Herein we report increased expression of TJP1 during the adaptive response mediating carfilzomib resistance in the LP-1/Cfz MM cell line. Moreover, increased TJP1 expression delineated a subset of relapsed/refractory MM patients on bortezomib-based therapy sharing an LP-1/Cfzlike phenotype characterized by activation of interacting transcriptional effectors of the Hippo signaling cascade (TAZ and TEAD1) and an adult tissue stem cell signature. siRNA-mediated knockdown of TJP1 or TAZ/TEAD1 partially sensitized LP-1/Cfz cells to carfilzomib. …

Vorinostat Renders The Replication-Competent Latent Reservoir Of Human Immunodeficiency Virus (Hiv) Vulnerable To Clearance By Cd8 T Cells., Julia A Sung, Katherine Sholtis, Jennifer Kirchherr, Joann D Kuruc, Cynthia L Gay, Jeffrey L Nordstrom, Catherine M Bollard, Nancie M Archin, David M Margolis

Pediatrics Faculty Publications

Latently human immunodeficiency virus (HIV)-infected cells are transcriptionally quiescent and invisible to clearance by the immune system. To demonstrate that the latency reversing agent vorinostat (VOR) induces a window of vulnerability in the latent HIV reservoir, defined as the triggering of viral antigen production sufficient in quantity and duration to allow for recognition and clearance of persisting infection, we developed a latency clearance assay (LCA). The LCA is a quantitative viral outgrowth assay (QVOA) that includes the addition of immune effectors capable of clearing cells expressing viral antigen. Here we show a reduction in the recovery of replication-competent virus from …

Transcriptomic Differentiation Underlying Marine‐To‐Freshwater Transitions In The South American Silversides Odontesthes Argentinensis And O. Bonariensis (Atheriniformes), Lily Hughes, Gustavo Somoza, Bryan Nguyen, James Bernot, Mariano Gonzalez-Castro, Juan Martin Diaz De Astarloa, Guillermo Orti

Computational Biology Institute

Salinity gradients are critical habitat determinants for freshwater organisms. Silverside fishes in the genus Odontesthes have recently and repeatedly transitioned from marine to freshwater habitats, overcoming a strong ecological barrier. Genomic and transcriptomic changes involved in this kind of transition are only known for a few model species. We present new data and analyses of gene expression and microbiome composition in the gills of two closely related silverside species, marine O. argentinensis and freshwater O. bonariensis and find more than three thousand transcripts differentially expressed, with osmoregulatory/ion transport genes and immune genes showing very different expression patterns across species. Interspecific …

Parasite Microbiome Project: Systematic Investigation Of Microbiome Dynamics Within And Across Parasite-Host Interactions., Nolwenn M Dheilly, Daniel Bolnick, Seth Bordenstein, Paul J Brindley, Cédric Figuères, Edward C Holmes, Joaquín Martínez Martínez, Anna J Phillips, Robert Poulin, Karyna Rosario

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Understanding how microbiomes affect host resistance, parasite virulence, and parasite-associated diseases requires a collaborative effort between parasitologists, microbial ecologists, virologists, and immunologists. We hereby propose the Parasite Microbiome Project to bring together researchers with complementary expertise and to study the role of microbes in host-parasite interactions. Data from the Parasite Microbiome Project will help identify the mechanisms driving microbiome variation in parasites and infected hosts and how that variation is associated with the ecology and evolution of parasites and their disease outcomes. This is a call to arms to prevent fragmented research endeavors, encourage best practices in experimental approaches, and …

Helminth Infection-Induced Malignancy., Paul J Brindley, Alex Loukas

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Infectious diseases cause more than 20% of cancers in the developing world [1]. About a dozen pathogens including Epstein-Barr virus and human T cell lymphocytotropic virus 1 are among the well-known examples. In addition, infection with several trematodes, which are eukaryotes, can cause malignancy. The International Agency for Research on Cancer categorizes infection with the fish-borne trematodes Opisthorchis viverrini and Clonorchis sinensis and the blood fluke Schistosoma haematobium as Group 1 biological carcinogens [2]. In addition to parasitism directly damaging development, health, and prosperity of infected populations, infection with these helminths leads to cholangiocarcinoma (CCA) (bile duct cancer) and squamous …

Praja Is Overexpressed In Glioblastoma And Contributes To Neural Precursor Development, Joshua Shin, Viveka Mishra, Eric Glasgow, Sobia Zaidi, Kazufumi Ohshiro, Lopa Mishra, Shuyun Rao, +Several Additional Authors

Medicine Faculty Publications

PRAJA, a RING-H2 E3 ligase, is abundantly expressed in brain tissues such as the cerebellum and frontal cortex, amongst others, and more specifically in neural progenitor cells as well as in multiple cancers that include glioblastomas. However, the specific role that Praja plays in neural development and gliomas remains unclear. In this investigation, we performed bioinformatic analyses to examine Praja1 and Praja2 expression across 29 cancer types, and observed raised levels of Praja1 and Praja2 in gliomas with an inverse relationship between Praja1 and apoptotic genes and Praja substrates such as Smad3. We analyzed the role of Praja in the …

Medical Genetics And Genomic Medicine In The United States Of America. Part 1: History, Demographics, Legislation, And Burden Of Disease., Carlos R Ferreira, Debra S Regier, Donald W Hadley, P Suzanne Hart, Maximilian Muenke

Pediatrics Faculty Publications

No abstract provided.

Alternative Splicing Promotes Tumour Aggressiveness And Drug Resistance In African American Prostate Cancer., Bi-Dar Wang, Kristin Ceniccola, Sujin Hwang, Ramez Andrawis, Anelia Horvath, Jennifer A Freedman, Jacqueline Olender, Stefan Knapp, Travers Ching, Lana Garmire, Vyomesh Patel, Mariano A Garcia-Blanco, Steven R Patierno, Norman H Lee

Pharmacology and Physiology Faculty Publications

linical challenges exist in reducing prostate cancer (PCa) disparities. The RNA splicing landscape of PCa across racial populations has not been fully explored as a potential molecular mechanism contributing to race-related tumour aggressiveness. Here, we identify novel genome-wide, race-specific RNA splicing events as critical drivers of PCa aggressiveness and therapeutic resistance in African American (AA) men. AA-enriched splice variants of PIK3CD, FGFR3, TSC2 and RASGRP2 contribute to greater oncogenic potential compared with corresponding European American (EA)-expressing variants. Ectopic overexpression of the newly cloned AA-enriched variant, PIK3CD-S, in EA PCa cell lines enhances AKT/mTOR signalling and increases proliferative …

Validating Candidate Congenital Heart Disease Genes In Drosophila., Jun-Yi Zhu, Yulong Fu, Adam Richman, Zhe Han

Pediatrics Faculty Publications

Genomic sequencing efforts can implicate large numbers of genes and de novo mutations as potential disease risk factors. A high throughput in vivo model system to validate candidate gene association with pathology is therefore useful. We present such a system employing Drosophila to validate candidate congenital heart disease (CHD) genes. The protocols exploit comprehensive libraries of UAS-GeneX-RNAi fly strains that when crossed into a 4×Hand-Gal4 genetic background afford highly efficient cardiac-specific knockdown of endogenous fly orthologs of human genes. A panel of quantitative assays evaluates phenotypic severity across multiple cardiac parameters. These include developmental lethality, larva and adult heart morphology, …

African-American Esophageal Squamous Cell Carcinoma Expression Profile Reveals Dysregulation Of Stress Response And Detox Networks., Hayriye Verda Erkizan, Kory Johnson, Svetlana Ghimbovschi, Deepa Karkera, Gregory Trachiotis, Houtan Adib, Eric P Hoffman, Robert G Wadleigh

Genomics and Precision Medicine Faculty Publications

BACKGROUND: Esophageal carcinoma is the third most common gastrointestinal malignancy worldwide and is largely unresponsive to therapy. African-Americans have an increased risk for esophageal squamous cell carcinoma (ESCC), the subtype that shows marked variation in geographic frequency. The molecular architecture of African-American ESCC is still poorly understood. It is unclear why African-American ESCC is more aggressive and the survival rate in these patients is worse than those of other ethnic groups.

METHODS: To begin to define genetic alterations that occur in African-American ESCC we conducted microarray expression profiling in pairs of esophageal squamous cell tumors and matched control tissues.

RESULTS: …

Il-18 Polymorphisms Contribute To Hepatitis B Virus-Related Cirrhosis And Hepatocellular Carcinoma Susceptibility In Chinese Population: A Case-Control Study., Zhi-Jun Dai, Xing-Han Liu, Meng Wang, Yan Guo, Wenge Zhu, Xiao Li, Shuai Lin, Tian Tian, Kang Liu, Yi Zheng, Peng Xu, Tianbo Jin, Xiaopeng Li

Biochemistry and Molecular Medicine Faculty Publications

IL-18 polymorphisms influence the transcriptional activity of the IL-18 gene and associated with various diseases. However, their relationships with hepatitis B virus-related liver diseases had not reached a consensus. So we conducted this case-control study with a view to clarifying the association. We included four groups: healthy controls, chronic hepatitis B virus (CHB) carriers, liver cirrhosis (LC) and hepatocellular carcinoma (HCC) groups with each group of 250 persons. Odd ratios (ORs) and 95% confidence intervals (95%CIs) with or without adjustment were calculated. Haplotype analysis was also performed. The results showed people carrying rs187238 CG genotype had a lower risk of …