Digital Commons Network^™

Association Of Impaired Linear Growth And Worse Neurodevelopmental Outcome In Infants With Single Ventricle Physiology: A Report From The Pediatric Heart Network Infant Single Ventricle Trial., Chitra Ravishankar, Victor Zak, Ismee A. Williams, David C. Bellinger, J William Gaynor, Nancy S. Ghanayem, Catherine D. Krawczeski, Daniel J. Licht, Lynn Mahony, Jane W. Newburger, Victoria L. Pemberton, Richard V. Williams, Renee Sananes, Amanda L. Cook, Teresa Atz, Svetlana Khaikin, Daphne T. Hsu, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: To describe neurodevelopmental outcomes in infants with single ventricle (SV) physiology and determine factors associated with worse outcomes.

STUDY DESIGN: Neurodevelopmental outcomes for infants with SV enrolled in a multicenter drug trial were assessed at 14 months of age using the Bayley Scales of Infant Development-II. Multivariable regression analysis was used to identify factors associated with worse outcomes.

RESULTS: Neurodevelopmental testing was performed at 14 ± 1 months in 170/185 subjects in the trial. Hypoplastic left heart syndrome was present in 59% and 75% had undergone the Norwood operation. Mean Psychomotor Developmental Index (PDI) and mental developmental index (MDI) …

Renal Function And Proteinuria After Successful Immunosuppressive Therapies In Patients With Fsgs., Ronald J. Hogg, Aaron Friedman, Tom Greene, Milena Radeva, Milos N. Budisavljevic, Jennifer Gassman, Debbie S. Gipson, J Ashley Jefferson, Eunice G. John, Frederick J. Kaskel, Asha Moudgil, Marva Moxey-Mims, Luis A. Ortiz, Jeffrey R. Schelling, William Schnaper, Tarak Srivastava, Howard Trachtman, V Matti Vehaskari, Craig Wong, Robert P. Woronieki, Scott K. Van Why, Anna Zolotnitskaya

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: In the FSGS Clinical Trial, 22 cyclosporine-treated and 20 mycophenolate/dexamethasone-treated patients experienced a complete or partial remission after 26 weeks, completed 52 weeks of treatment, and were studied through 78 weeks. Herein, changes in the urine protein/creatinine ratio (UP/C) and estimated GFR (eGFR) throughout the entire study period are defined.

DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: The FSGS Clinical Trial, which was conducted from November 2004 to January 2010, enrolled patients aged 2-40 years, with eGFR ≥40 ml/min per 1.73 m(2) and UP/C >1 mg/mg after ≥4 weeks of corticosteroid therapy. Both groups received lisinopril or losartan throughout …

Food Venue Choice, Consumer Food Environment, But Not Food Venue Availability Within Daily Travel Patterns Are Associated With Dietary Intake Among Adults, Lexington Kentucky 2011, Alison A. Gustafson, Jay W. Christian, Sarah Lewis, Kate Moore, Stephanie Jilcott

Dietetics and Human Nutrition Faculty Publications

OBJECTIVE: The retail food environment may be one important determinant of dietary intake. However, limited research focuses on individuals' food shopping behavior and activity within the retail food environment. This study's aims were to determine the association between six various dietary indicators and 1) food venue availability; 2) food venue choice and frequency; and 3) availability of healthy food within food venue.

METHODS: In Fall, 2011, a cross-sectional survey was conducted among adults (n=121) age 18 years and over in Lexington, Kentucky. Participants wore a global position system (GPS) data logger for 3-days (2 weekdays and 1 weekend day) to …

Tree Climbing And Human Evolution, Vivek V. Venkataraman, Thomas S. Kraft, Nathaniel J. Dominy

Dartmouth Scholarship

Paleoanthropologists have long argued—often contentiously—about the climbing abilities of early hominins and whether a foot adapted to terrestrial bipedalism constrained regular access to trees. However, some modern humans climb tall trees routinely in pursuit of honey, fruit, and game, often without the aid of tools or support systems. Mortality and morbidity associated with facultative arboreality is expected to favor behaviors and anatomies that facilitate safe and efficient climbing. Here we show that Twa hunter–gatherers use extraordinary ankle dorsiflexion (>45°) during climbing, similar to the degree observed in wild chimpanzees. Although we did not detect a skeletal signature of dorsiflexion …

Website Usage And Weight Loss In A Free Commercial Online Weight Loss Program: Retrospective Cohort Study, Kevin O Hwang, Jing Ning, Amber W Trickey, Christopher N Sciamanna

Faculty, Staff and Student Publications

BACKGROUND: Online weight loss programs are increasingly popular. However, little is known about outcomes and associations with website usage among members of free online weight loss programs.

OBJECTIVE: This retrospective cohort study examined the association between website usage and weight loss among members of a free commercial online weight loss program (SparkPeople).

METHODS: We conducted a retrospective analysis of a systematic random sample of members who joined the program during February 1 to April 30, 2008, and included follow-up data through May 10, 2010. The main outcome was net weight change based on self-reported weight. Measures of website usage included …

Long-Term Upregulation Of Inflammation And Suppression Of Cell Proliferation In The Brain Of Adult Rats Exposed To Traumatic Brain Injury Using The Controlled Cortical Impact Model, Sandra A. Acosta, Naoki Tajiri, Kazutaka Shinozuka, Hiroto Ishikawa, Bethany Grimmig, David M. Diamond, Paul R. Sanberg, Paula C. Bickford, Yuji Kaneko, Cesario V. Borlongan

Psychology Faculty Publications

The long-term consequences of traumatic brain injury (TBI), specifically the detrimental effects of inflammation on the neurogenic niches, are not very well understood. In the present in vivo study, we examined the prolonged pathological outcomes of experimental TBI in different parts of the rat brain with special emphasis on inflammation and neurogenesis. Sixty days after moderate controlled cortical impact injury, adult Sprague-Dawley male rats were euthanized and brain tissues harvested. Antibodies against the activated microglial marker, OX6, the cell cycle-regulating protein marker, Ki67, and the immature neuronal marker, doublecortin, DCX, were used to estimate microglial activation, cell proliferation, and neuronal …

Impulsivity And Self-Control During Intertemporal Decision Making Linked To The Neural Dynamics Of Reward Value Representation, Koji Jimura, Maria S. Chushak, Todd S. Braver

Open Access Publications

A characteristic marker of impulsive decision making is the discounting of delayed rewards, demonstrated via choice preferences and choice-related brain activity. However, delay discounting may also arise from how subjective reward value is dynamically represented in the brain when anticipating an upcoming chosen reward. In the current study, brain activity was continuously monitored as human participants freely selected an immediate or delayed primary liquid reward and then waited for the specified delay before consuming it. The ventromedial prefrontal cortex (vmPFC) exhibited a characteristic pattern of activity dynamics during the delay period, as well as modulation during choice, that is consistent …

Coordinated Dynamic Gene Expression Changes In The Central Nucleus Of The Amygdala During Alcohol Withdrawal., Kate Freeman, Mary M. Staehle, Rajanikanth Vadigepalli, Gregory E Gonye, Babatunde A Ogunnaike, Jan B Hoek, James S Schwaber

College of Science & Mathematics Departmental Research

BACKGROUND: Chronic alcohol use causes widespread changes in the cellular biology of the amygdala's central nucleus (CeA), a GABAergic center that integrates autonomic physiology with the emotional aspects of motivation and learning. While alcohol-induced neurochemical changes play a role in dependence and drinking behavior, little is known about the CeA's dynamic changes during withdrawal, a period of emotional and physiologic disturbance.

METHODS: We used a qRT-PCR platform to measure 139 transcripts in 92 rat CeA samples from control (N = 33), chronically alcohol exposed (N = 26), and withdrawn rats (t = 4, 8, 18, 32, and 48 hours; N …

Determinants Of Negative Pathways To Care And Their Impact On Service Disengagement In First-Episode Psychosis., Kelly K. Anderson, Rebecca Fuhrer, Norbert Schmitz, Ashok K Malla

Epidemiology and Biostatistics Publications

PURPOSE: Although there have been numerous studies on pathways to care in first-episode psychosis (FEP), few have examined the determinants of the pathway to care and its impact on subsequent engagement with mental health services.

METHODS: Using a sample of 324 FEP patients from a catchment area-based early intervention (EI) program in Montréal, we estimated the association of several socio-demographic, clinical, and service-level factors with negative pathways to care and treatment delay. We also assessed the impact of the pathway to care on time to disengagement from EI services.

RESULTS: Few socio-demographic or clinical factors were predictive of negative pathways …

Acute Alcohol Consumption Impairs Controlled But Not Automatic Processes In A Psychophysical Pointing Paradigm., Kevin Johnston, Brian Timney, Melvyn A Goodale

Brain and Mind Institute Researchers' Publications

Numerous studies have investigated the effects of alcohol consumption on controlled and automatic cognitive processes. Such studies have shown that alcohol impairs performance on tasks requiring conscious, intentional control, while leaving automatic performance relatively intact. Here, we sought to extend these findings to aspects of visuomotor control by investigating the effects of alcohol in a visuomotor pointing paradigm that allowed us to separate the influence of controlled and automatic processes. Six male participants were assigned to an experimental "correction" condition in which they were instructed to point at a visual target as quickly and accurately as possible. On a small …

An Experimental Study Of The Interface Pressure Profile During Level Walking Of A New Suspension System For Lower Limb Amputees, A. Eshraghi, Noor Azuan Abu Osman, H. Gholizadeh, S. Ali, S.K. Sã¦Varsson, Wan Abu Bakar Wan Abas

Research Publications (2011 to 2015)

Background: Different suspension systems that are used within prosthetic devices may alter the distribution of pressure inside the prosthetic socket in lower limb amputees. This study aimed to compare the interface pressure of a new magnetic suspension system with the pin/lock and Seal-In suspension systems. Methods: Twelve unilateral transtibial amputees participated in the study. The subjects walked on a level walkway at a self-selected speed. The resultant peak pressure with the three different suspension systems was recorded using F-socket transducers. Findings: There were significant statistical differences between the three studied suspension systems. Pair-wise analyses revealed that the mean peak pressure …

Interface Pressure In Transtibial Socket During Ascent And Descent On Stairs And Its Effect On Patient Satisfaction, S. Ali, Noor Azuan Abu Osman, A. Eshraghi, H. Gholizadeh, N.A.B. Abd Razak, Wan Abu Bakar Wan Abas

Research Publications (2011 to 2015)

Background Transtibial amputees encounter stairs and steps during their daily activities. The excessive pressure between residual limb/socket may reduce the walking capability of transtibial prosthetic users during ascent and descent on stairs. The purposes of the research were to evaluate the interface pressure between Dermo (shuttle lock) and Seal-In X5 (prosthetic valve) interface systems during stair ascent and descent, and to determine their satisfaction effects on users. Methods Ten amputees with unilateral transtibial amputation participated in the study. Interface pressure was recorded with F-socket transducer (9811E) during stair ascent and descent at self-selected speed. Each participant filled in a questionnaire …

The Validity And Reliability Of Motion Analysis In Patellar Tendon Reflex Assessment, Lai Kuan Tham, Noor Azuan Abu Osman, Wan Abu Bakar Wan Abas, Kheng Seang Lim

Research Publications (2011 to 2015)

Background: The deep tendon reflex assessments that are essential to the accurate diagnosis of neurological or neuromuscular disorders are conducted subjectively in clinical neurology. Our aim was to assess deep tendon reflexes objectively with a new reflex quantification method. Methodology/Principal Findings: The present study used a motion analysis technique to collect quantitative measurements for both the input and output of normal patellar tendon reflex. Reflex responses were measured as knee angles. The patellar tendon reflexes of 100 healthy subjects were examined using 6 levels of tendon taps, where all the assessments were captured using motion capture system. A linear relationship …

Community Knowledge, Attitude And Practice About Malaria In A Low Endemic Setting Of Shewa Robit Town, Northeastern Ethiopia, Andargie Abate, Abraham Degarege, Berhanu Erko

Journal Articles: Epidemiology

BACKGROUND: Since malaria is one of the foremost public health problems in Ethiopia, assessment of situation of the disease, and communities' knowledge and perceptions about malaria is necesary to institute appropriate preventive and control measures. Thus, the aim of this study was to assess malaria prevalence and knowledge, attitude and practice (KAP) about the disease among ShewaRobit Town community, northeastern Ethiopia.

METHODS: A community-based cross-sectional study was conducted in Shewa Robit Town from October to November 2011. A multi-stage random sampling technique was used to select the study participants. A total of 425 individuals were examined for malaria using thin …

Gaps In Survey Data On Cancer In American Indian And Alaska Native Populations: Examination Of Us Population Surveys, 1960-2010, Shinobu Watanabe-Galloway, Tinka Duran, Jim P. Stimpson, Corey Smith

Journal Articles: Epidemiology

INTRODUCTION: Population-based data are essential for quantifying the problems and measuring the progress made by comprehensive cancer control programs. However, cancer information specific to the American Indian/Alaska Native (AI/AN) population is not readily available. We identified major population-based surveys conducted in the United States that contain questions related to cancer, documented the AI/AN sample size in these surveys, and identified gaps in the types of cancer-related information these surveys collect.

METHODS: We conducted an Internet query of US Department of Health and Human Services agency websites and a Medline search to identify population-based surveys conducted in the United States from …

The Impact Of Racial Identity, Masculinity, And Academic Self-Concept On The Academic Achievement Of African American Male High School Students, Howard Lloyd

Theses and Dissertations--Educational, School, and Counseling Psychology

Previous literature has evidenced that young African American males are experiencing less academic success than their Caucasian male and African American female counterparts (Davis, Williams, & Williams, 2004; Flores, 2007). The deceleration of achievement in this population has spawned some inquiry into the struggles of African American students. However, investigators have primarily examined differences in sex, school attributes, socioeconomic status, family structure, and other external factors. Previous research has also highlighted the unique obstacles young African American men face in education settings. While researchers have identified several external predictors of academic achievement among African American males, scant information relates to …

Task-Based Noise Exposures For Farmers Involved In Grain Production, Michael J. Humann, Wayne T. Sanderson, Kelley J. Donham, Kevin M. Kelly

Epidemiology and Environmental Health Faculty Publications

Few studies have been done examining noise exposures associated with agricultural tasks. This study was conducted to address that research gap by calculating the noise exposures for tasks and equipment associated with grain production and assessing the variability in those exposures. An additional aim of this study was to identify tasks and equipment that could be targeted for intervention strategies as a means toward reducing the total noise exposures of farmers and farm workers. Through the use of personal noise dosimetry and direct observation, over 30,000 one-minute noise exposure measurements and corresponding task and equipment data were collected on 18 …

Willingness To Undergo A Repeat Liver Biopsy Among Hiv/Hepatitis C Virus-Coinfected And Hepatitis C Virus-Monoinfected Patients, Valerianna K Amorosa, Omowunmi Aibana, Norah J Shire, Zachariah Dorey-Stein, Thomas Ferrara, Joanne Gilmore, Jay R Kostman, Vincent Lo Re

Faculty, Staff and Student Publications

BACKGROUND: Guidelines for chronic hepatitis C virus (HCV) management have recommended that a liver biopsy be repeated at 3-year intervals for HIV/HCV-coinfected patients and 5-year intervals for those with HCV monoinfection to assess fibrosis progression. However, it is unclear if patients are willing to repeat this procedure.

OBJECTIVE: To determine the prevalence and factors, particularly HIV coinfection, associated with willingness to repeat a liver biopsy.

METHODS: A questionnaire was administered to 235 HCV-infected patients (113 with HIV coinfection) between January 2008 and June 2011 who previously underwent liver biopsy. The main outcome was self-reported willingness to repeat the biopsy. The …

Cattle-Related Injuries And Farm Management Practices On Kentucky Beef Cattle Farms, Steven R. Browning, Susan C. Westneat, Wayne T. Sanderson, Deborah B. Reed

Epidemiology and Environmental Health Faculty Publications

While working on farms with livestock increases the risk of injury among farm workers in comparison to other commodity farms, few studies have examined the role offarm management practices in association with the risk of cattle-related injury. We examined the farm management practices of Kentucky beef cattle farms in association with self-reported rates of cattle-related injuries among workers. We conducted a mail survey of a random sample of 2,500 members of the Kentucky Cattlemen's Association. Results from 1,149 farm operators who were currently raising beef cattle and provided complete survey response are reported. During the busy season, the principal operator …

Lead-Based Paint Awareness, Work Practices, And Compliance During Residential Construction And Renovation, James D. Blando, Nickita Antoine, Daniel Lefkowitz

Community & Environmental Health Faculty Publications

The U.S. Environmental Protection Agency recently implemented the Renovation, Repair and Painting (RRP) rule that applies to pre-1978 residences because of the potential presence of lead-based paint. Enforcement of this rule may be difficult and therefore it is crucial to understand the awareness and beliefs of contractors and the general public because these will likely be major determinants of exposures resulting from residential renovation work. The study described in this article utilized two mailed surveys: one directed to the general public and the other directed to contractors. The surveys were conducted in New Jersey and Virginia. Field observations were also …

Predicting Barriers To Primary Care For Patients With Disabilities: A Mixed Methods Study Of Practice Administrators, Jennifer Renee Pharr, Michelle Chino

Environmental & Global Health Faculty Research

Background. People with disabilities continue to be identified as a group who experience disparate health/health care. They are less likely to engage in some health care services. Structural barriers are often identified as one of the reasons for the underutilization of some health care services by people with disabilities. However, to date no study has been conducted to understand why structural barriers persist twenty years after the Americans with Disabilities Act (ADA) became law.

Objectives. We examined the relationship between primary care practice administrators’ knowledge of the ADA and the number of accessibility barriers that patients with mobility disabilities might …

De Novo Orfs In Drosophila Are Important To Organismal Fitness And Evolved Rapidly From Previously Non-Coding Sequences, Josephine A. Reinhardt, Betty M. Wanjiru, Alicia T. Brant, Perot Saelao, David J. Begun, Corbin D. Jones

Biology

How non-coding DNA gives rise to new protein-coding genes (de novo genes) is not well understood. Recent work has revealed the origins and functions of a few de novo genes, but common principles governing the evolution or biological roles of these genes are unknown. To better define these principles, we performed a parallel analysis of the evolution and function of six putatively protein-coding de novo genes described in Drosophila melanogaster. Reconstruction of the transcriptional history of de novo genes shows that two de novo genes emerged from novel long non-coding RNAs that arose at least 5 MY prior to evolution …

The Forms Of Bullying Scale (Fbs): Validity And Reliability Estimates For A Measure Of Bullying Victimization And Perpetration In Adolescence, Therese M. Shaw, Julian J. Dooley, Donna S. Cross, Stephen R Zubrick, Stacey K. Waters

Research outputs 2013

The study of bullying behavior and its consequences for young people depends on valid and reliable measurement of bullying victimization and perpetration. Although numerous self-report bullying-related measures have been developed, robust evidence of their psychometric properties is scant, and several limitations inhibit their applicability. The Forms of Bullying Scale (FBS), with versions to measure bullying victimization (FBS-V) and perpetration (FBS-P), was developed on the basis of existing instruments, for use with 12-to 15-year-old adolescents to economically, yet comprehensively measure both bullying perpetration and victimization. Measurement properties were estimated. Scale validity was tested using data from 2 independent studies of 3,496 …

Characteristics And Quality Of Life Of Patients Presenting To Cancer Support Centres: Patient Rated Outcomes And Use Of Complementary Therapies, Bonnie J. Furzer, Kemi E. Wright, Anna S. Petterson, Karen E. Wallman, Timothy R. Ackland, David Jl Joske

Research outputs 2013

Background: In order to effectively target and provide individualised patient support strategies it is crucial to have a comprehensive picture of those presenting for services. The purpose of this study was to determine the characteristics and patient rated outcomes of individuals presenting to SolarisCare cancer support centres and their choices regarding complementary and integrated therapies (CIT).Methods: A cohort with a current or previous cancer diagnosis aged 18 - 87 years presenting to a SolarisCare centre during a 5-day period completed a questionnaire. Four SolarisCare centres participated in the trial including regional and metropolitan locations. Outcomes included medical and demographic characteristics, …

Lifestyle Factors, Medication Use And Risk For Ischaemic Heart Disease Hospitalisation: A Longitudinal Population-Based Study, Anthony S. Gunnell, K Einarsdottir, Daniel A. Galvao, S Joyce, S Tomlin, Vicki J. Graham, Caroline Mcintyre, Robert U. Newton, T Briffa

Research outputs 2013

Background:Lifestyle factors have been implicated in ischaemic heart disease (IHD) development however a limited number of longitudinal studies report results stratified by cardio-protective medication use.Purpose:This study investigated the influence of self-reported lifestyle factors on hospitalisation for IHD, stratified by blood pressure and/or lipid-lowering therapy.Methods:A population-based cohort of 14,890 participants aged 45+ years and IHD-free was identified from the Western Australian Health and wellbeing Surveillance System (2004 to 2010 inclusive), and linked with hospital administrative data. Adjusted hazard ratios for future IHD-hospitalisation were estimated using Cox regression.Results:Current smokers remained at higher risk for IHD-hospitalisation (adjusted HR=1.57; 95% CI: 1.22-2.03) after adjustment …

Markers Of Circulating Tumour Cells In The Peripheral Blood Of Patients With Melanoma Correlate With Disease Recurrence And Progression, Anna L. Reid, M Millward, Robert Pearce, M Lee, M Frank, A Ireland, L Monshizadeh, Tapan Rai, P Heenan, Sandra Medic, P Kumarasinghe, Melanie R. Ziman

Research outputs 2013

Background: Multimarker quantitative real-time polymerase chain reaction (qRT-PCR) represents an effective method for detecting circulating tumour cells in the peripheral blood of patients with melanoma.

Objectives: To investigate whether the phenotype of circulating melanoma cells represents a useful indicator of disease stage, recurrence and treatment efficacy.

Methods: Peripheral blood was collected from 230 patients with melanoma and 152 healthy controls over a period of 3 years and 9 months. Clinical data and blood samples were collected from patients with primary melanoma (early stages, 0-II, n = 154) and metastatic melanoma (late stages, III-IV, n = 76). Each specimen was examined …

Internet-Based Photoaging Within Australian Pharmacies To Promote Smoking Cessation: Randomized Controlled Trial, Oksana Burford, Moyez Jiwa, Owen B. Carter, Richard Parsons, Delia Hendrie

Research outputs 2013

Background: Tobacco smoking leads to death or disability and a drain on national resources. The literature suggests that cigarette smoking continues to be a major modifiable risk factor for a variety of diseases and that smokers aged 18-30 years are relatively resistant to antismoking messages due to their widely held belief that they will not be lifelong smokers. Objective: To conduct a randomized controlled trial (RCT) of a computer-generated photoaging intervention to promote smoking cessation among young adult smokers within a community pharmacy setting. Methods: A trial was designed with 80% power based on the effect size observed in a …

Health-Related Quality Of Life And Life Satisfaction In Colorectal Cancer Survivors: Trajectories Of Adjustment, Jeff Dunn, Shu Kay Ng, William Breitbart, Joanne Aitken, Pip Youl, Peter D. Baade, Suzanne K. Chambers

Research outputs 2013

Background: This longitudinal study describes the five year trajectories of health-related quality of life (HR-QOL) and life satisfaction in long term colorectal cancer survivors.Patients and methods: A population-based sample of 1966 colorectal cancer survivors were surveyed at six time points from five months to five years post-diagnosis. Predictor variables were: socio-demographic variables, optimism; cancer threat appraisal; perceived social support. Quality of life was assessed with the Functional Assessment of Cancer Therapy-Colorectal (HR-QOL); and the Satisfaction with Life Scale. Growth mixture models were applied to identify trajectory classes and their predictors.Results: Distinct adjustment trajectories were identified for HR-QOL and life satisfaction. …

Exploring Wellbeing In Older Male Farmers In Western Australia, Jessica L. Mckee

Theses : Honours

In the context of an ageing population it has become increasingly important to identify the determinants of wellbeing in older adulthood. A review of the literature relevant to wellbeing and strengths relevant to older male farmers in Australia was conducted. This body of knowledge was identified to be sparse. Existing literature on farming primarily had a deficits focus, and only a small number of qualitative studies were specific to older male farmers. Four broad, overlapping areas representing the meaning of wellbeing were identified as potentially important: farming work; connectedness; the land; health and wellbeing. The inter-connected nature of farming life …

Ash2 Acts As An Ecdysone Receptor Coactivator By Stabilizing The Histone Methyltransferase Trr., Albert Carbonell, Alexander Mazo, Florenci Serras, Montserrat Corominas

Department of Biochemistry and Molecular Biology Faculty Papers

The molting hormone ecdysone triggers chromatin changes via histone modifications that are important for gene regulation. On hormone activation, the ecdysone receptor (EcR) binds to the SET domain-containing histone H3 methyltransferase trithorax-related protein (Trr). Methylation of histone H3 at lysine 4 (H3K4me), which is associated with transcriptional activation, requires several cofactors, including Ash2. We find that ash2 mutants have severe defects in pupariation and metamorphosis due to a lack of activation of ecdysone-responsive genes. This transcriptional defect is caused by the absence of the H3K4me3 marks set by Trr in these genes. We present evidence that Ash2 interacts with Trr …