The Kansas Intellectual and Developmental Disabilities Research Center
(Formerly the Kansas Mental Retardation and Developmental Disabilities Research Center)
Volume 8, No. 10, October-November 2007
This month, we get a refresher course on some of the excellent services the KIDDRC Cores offer investigators - plus some news.
The KUMC Microarray Facility
Clark Bloomer, Project Manager
The KUMC Microarray Facility would like to inform the KIDDRC community of some recent additions to our personnel and offered services. In March the Microarray Facility added Yafen Niu as a Research Associate to the facilities staff. Yafen performs an integral role in the microarray services offered by the facility as well as a lead role in the newly implemented RNA isolation service. The facility is also servicing the new Gene Array and Exon Array expression platforms for the Affymetrix GeneChip system. The Human SNP
5.0 (500k SNP) and 6.0 (1M SNP) are the latest genomic mapping arrays that will be serviced by the Microarray Facility. In support of investigators conducting genomic mapping projects, the facility has also added DNA isolation services. For more information, see: http://www2.kumc.edu/siddrc/microarray.
The Bioinformatics Core at KU Medical Center
Stan R. Svojanovsky, Ph.D.
New microarray technologies and data evaluation software allow us to investigate many genes at once and determine which are expressed in a particular cell type. We use this powerful technology to investigate which genes are turned on and off in treated versus healthy tissues from various organisms and to determine the biological relevance of the genes and the biological pathway between different classes of genes.
The KUMC Bioinformatics Core was established with funding from NIH Grant Number P20 RR016475 from the INBRE Program of the National Center for Research Resources (Kansas IDeA Network of Biomedical Research Excellence (K-INBRE) and supported by The Smith Intellectual Developmental Disabilities Research Center (SIDDRC) NICHD HD 02528. The primary goal of this core is to provide high quality collaborative services for genomic, proteomic and biomedical data analysis to investigators at KUMC other K-INBRE participants and KIDDRC investigators on either campus.
We provide assistance in three phases of microarray data analysis. In the primary phase, data, including numerical signal intensity and the probe accession number, are formatted, normalized and transferred into Affymetrix Data Mining Tool. The data are saved in Microsoft Excel format, which is compatible with Affymetrix, GeneSpring and StatMost software. Data are archived as password-protected copies maintained in a CD library, on computer hard drives and on the K-INBRE server. Databases are created using Affymetrix GCOS (GeneChip Operating System) software and populated via GCOS Data Transfer Tool into Affymetrix Data Mining Tool. Numbers of genes present in the target samples are determined and ranked according to fold change relative to control samples. Statistical significance for changes in expression is determined using StudentÕs t-test. Visual information on changes in gene expression for all probe sets is represented via scatter plots, histograms and fold change graphs.
In the secondary phase, additional data mining is conducted based on the specific aspects of the experiment and the investigatorÕs requirements. This usually includes reordering of the data, data filtration, additional plots, and cluster analyses. We also provide information on protein descriptions and biological pathways using Affymetrix NetAffx web site, GeneSpring GX, Ingenuity Pathway Analysis and other relevant software platforms and databases.
Tertiary analysis consists of more detailed analysis of the microarray data, including mining a specific group (cluster) of genes of interest. Comparisons of different clusters of genes and Principal Component Analysis (PCA) to reveal and quantify the impact of the principal gene in a given cluster are conducted using GeneSpring GX software. Location of sequences and specific genes on the genome and the degree of sequence similarity is determined using BLAST and BLAT analysis with publicly available genome databases.
For more information, please visit our web page:
Biobehavioral Measurement: Rodent Behavioral Testing
Jonathan Pinkston, Ph.D. Biobehavioral Core Coordinator
The Biobehavioral Measurement Core (BMC) provides KIDDRC investigators with a host of resources related to behavioral measurement. In addition to experimental design, programming, and instrumentation design, the BMC also manages and controls resources related to rodent behavioral testing. Many investigators trained in pharmacology, medicine, or molecular biology underutilize behavioral procedures or, when they are applied, use procedures that are less than the state of the art. Often the dearth in behavioral procedures is the consequence of training that has de-emphasized behavioral research and many researchers simply are not familiar with the complexities of behavioral experimentation. After all, one cannot be a specialist in everything.
And that is where the BMC comes in: we have a staff of behavior specialists with backgrounds in animal learning, psychopharmacology, and behavioral neuroscience to provide expertise in these areas and aid in adding behavior dimensions to your research. The BMC is a unique opportunity for KIDDRC investigators.
Currently, the BMC manages two resources for rodent behavioral testing. At the KU campus in Lawrence, renovations have been completed for the Complex Behavior and Learning Facility, located in Malott Hall. At present, equipment is being moved into the new facility. The various apparatuses and testing batteries will be made available as they come online. The full suite of equipment will provide for experimentation with transgenic and knockout mice to examine a broad range of brain and psychological processes.
The BMCÕs rodent testing aspect also has a presence at KUMC. The Rodent Behavior Facility (RBF) counterpoints the facility in Lawrence. Over the past several years, investigator usage of the rodent testing resources has greatly increased for the RBF. The swell of requests has prompted a new addition to the capabilities at the KUMC campus. The new addition will occupy a 500 square-foot laboratory space in the new KLSIC building and will be dedicated solely to the examination of rat behavior. The existing facility in the LAR building will continue to service the interests of researchers using mouse models.
Together, the two facilities currently support investigations of rodent models in several areas of research, including schizophrenia, stereotypy, HuntingtonÕs Disease, AlzheimerÕs Disease, diabetes, spinal injury and recovery, ALS, nutritional-related cognitive impairments, and impulse-control disorders. The breadth of research projects speaks to the range of domains to which our skills are applicable. So, when it comes time to consider systems-level experimentation, the BMC stands ready. We look forward to helping our investigators meet the needs of their projects and to the generation of collaborative research enterprise. Those interested in adding state-of-the-art behavioral testing to their existing projects should visit the BMC website at http://kiddrc.kumc.edu/coreb.html for more information.
Raymond Cheung, Assistant Director for Information Technology, Life Span Institute
The Ticket Tracker System, an online system that tracks the service requests of KIDDRC affiliated investigators, has been in use by Core B – Biobehavioral Measurement staff for more than 2 months. The system for Core C - Research Design and Analysis - will go live by the end of fall semester. The Core C staff is currently learning the process and reviewing details. Core D, Integrative Imaging, is still working with the software developer to customize their forms and reports and will have the system ready to use soon. Stay tuned for the progress. You can access Ticket Tracker online at the following URLs or you can simply call the core coordinators as usual and they will initiate the request for you.
Core B: http://www2.ku.edu/~lsi/cgi-bin/tracker/newrequest.php
Core C: http://www2.ku.edu/~lsi/cgi-bin/CoreCtracker/newrequest.php
A one-time administrative supplement to our P30 will support the dissemination of the highly successful program of LSI Peruvian affiliate, Centro Ann Sullivan del Peracross Peru and to other third world countries. CASP, directed by Liliana Mayo, who received her doctorate from KU, and Judith LeBlanc, KU Professor Emeritus, is a comprehensive model program for children and adults with developmental disabilities and their families.
CASP has received international awards and recognition for its highly sustainable family-based holistic approach grounded in evidence-based practices. CASP attracts faculty and students from KU and other universities who teach and learn in the school set in urban Lima. Several KIDDRC investigators have consulted with CASP in recent years including Steve Warren, Steve Schroeder, Matt Reese, and Eva Horn.
The supplement will support the development, testing and evaluation of an online system to allow CASPÕs video-based training modules to be accessible through the Internet via technologies that can function in regions with very low bandwidth infrastructure based on the University of IowaÕs Global Campus Network.
Karen Henry, LSI Assistant Director for Communications and a Core A staff member, will serve as project coordinator working with a CASP counterpart.
The Eighth Annual Summer Institute on Randomized Clinical Trials Involving Behavioral Interventions, organized by the NIH Office of Behavioral and Social Sciences Research, is scheduled for July 13 - 25, 2008, the Airlie Conference Center in Airlie Virginia, about 60 minutes driving time from Washington, DC and surrounding airports.
objective of the Institute is to provide a thorough grounding in the
conduct of randomized clinical trials to researchers and health professionals
interested in developing competence in the planning, design, and execution of
clinical trials involving behavioral or social interventions.
APPLICATIONS DUE JANUARY 31, 2008: Applications for 2008 must be submitted electronically. The application instructions are posted at http://www.blsweb.net/app2attend/
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Ronald P. Abeles, Ph.D.
Special Assistant to the Director
Office of Behavioral and Social Sciences Research
National Institutes of Health
Bldg. 31C, Rm. B1C19, MSC 2027
Bethesda, MD 20892-2027
Funded by NICHD HD048528
Kate Saunders, Ph.D., Principal Investigator, LSI Senior Scientist and KIDDRC Investigator
Many individuals with mental retardation (MR) read at levels below what might be expected based on other cognitive skills. Further, reading instruction historically has emphasized sight words, and this emphasis limits reading vocabulary to words that have been taught directly. There is a critical need for effective methods to teach word-attack, or decoding, skills to this difficult-to-teach population. Word-attack skills enable reading words that have not been taught directly.
In the literature on reading instruction for normally developing children, the major scientific development of the last few decades has been the identification of prerequisite and component skills that help to make decoding instruction successful. There is now incontrovertible evidence that phonological awareness, especially the ability to perceive sounds that make up spoken syllables, facilitates the acquisition of word-attack skills. Examples of phonological awareness include recognizing rhyming words, and recognizing that several words begin with the same sound. Phonemes are the smallest within-syllable units of sound that make a difference to meaning. It is important to note that learning to produce individual phonemes to corresponding printed letters (a part of phonics instruction) does not automatically ensure the awareness of phonemes within syllables. This is because phonemes within syllables are Ōsmeared together,Ķ they do not have discrete boundaries (this characteristic is called coarticulation).
Our long-term goal is to develop computerized instructional programming to teach foundational skills for reading to individuals with MR. The current project will take a step towards that goal by addressing the most neglected area of instruction for this population: the critical early reading skills of phonological awareness and the related concept that print maps the sounds that comprise syllables. The scientific foundation for our work lies in the conclusion of the National Reading Panel (2000) that phonological-awareness training that involves linking letters to sub-syllable sounds is more effective than training that is conducted only in the auditory mode. Thus, we plan to study the development of these skills using a word-construction task, in which the participants build words that they hear by touching individual letters in a pool of letters on a touch-sensitive computer screen. The word-construction procedures have several benefits. They promote left-to-right scanning and attention to each letter in a word. Further, if carefully composed sets of words that have subsyllable components in common are taught, these procedures can simultaneously promote the development of generalized sound-print relations and phonological awareness.
We will know that a participant has learned generalized skills when the participant can construct words that are composed of new combinations of sound-letter relations contained in words that the participant has learned to construct. For example, if a participant learns to construct the words cat, rat, and ran, and then proves able to construct can, even though can has not been taught, s/he has demonstrated generalization of the sound-letter relations across words. Further, our work has shown that it is not necessary for participants to be able to read words before learning to construct them. Given that the word construction task teaches component skills of individual-word reading, it is important that word-construction training can occur prior to or in conjunction with learning to read the words. This is an unstudied approach to establishing foundational skills in individuals with MR.
The project is being carried out with adults served by Community Living Opportunities and by Cottonwood, in Lawrence. Children participants come from the Educare preschool in the Dole building and we are planning for an expansion to children with intellectual disabilities in the Lawrence Public Schools. Four graduate students within the Department of Applied Behavioral Sciences are working on the project: Janna Skinner, Tanya Bayhnam, Katey Schmidt, and Megan Weaver.