The effects of the polyglutamine repeat protein ataxin-1 on the UbL-UBA protein A1Up.

The ataxin-1 interacting ubiquitin-like protein (A1Up) contains an amino-terminal ubiquitin-like (UbL) region, four stress-inducible, heat shock chaperonin-binding motifs (STI1), and an ubiquitin-associated domain (UBA) at the carboxyl terminus of A1Up. Although proteins that have both an UbL and UBA domain are thought to play a crucial role in proteasome-mediated activities, few are characterized, except for hHR23A/B. Similar to other UbL-containing proteins, the UbL of A1Up is essential for the interaction of A1Up with the S5a subunit of the 19S proteasome.

Childhood adversity, monoamine oxidase a genotype, and risk for conduct disorder.

Background: Very little is known about how different sets of risk factors interact to influence risk for psychiatric disorder.

Objective: To replicate a recent report of a genotype-environment interaction that predicts risk for antisocial behavior in boys.

Design: Characterizing risk for conduct disorder in boys in association with monoamine oxidase A genotype and exposure to familial adversity, defined by interparental violence, parental neglect, and inconsistent discipline.

No evidence for linkage or association of neuregulin-1 (NRG1) with disease in the Irish study of high-density schizophrenia families (ISHDSF).

The neuregulin-1 gene (NRG1) at chromosome 8p21-22 has been implicated as a schizophrenia susceptibility gene in Icelandic, Scottish, Irish and mixed UK populations. The shared ancestry between these populations led us to investigate the NRG1 polymorphisms and appropriate marker haplotypes for linkage and/or association to schizophrenia in the Irish study of high-density schizophrenia families (ISHDSF). Neither single-point nor multi-point linkage analysis of NRG1 markers gave evidence for linkage independent of our pre-existing findings telomeric on 8p.

The utilization of a 3-dimensional noncoplanar treatment plan to avoid pacemaker complications.

Treatment planning of thoracic patients having upper lobe lesions and a pacemaker presents quite a challenge. It is necessary to avoid the pacemaker as well as other critical structures in order to deliver the prescribed dose for local control. This case demonstrates the utilization of noncoplanar beams and asymmetric fields to limit the radiation dose to the pacemaker.

Linkage studies of schizophrenia.

The study of schizophrenia genetics has revealed much about the disease but none of the essential secrets of its etiology, so far, for numerous reasons. First, schizophrenia is a complex trait, influenced by both genes and environment. Second, it appears to be a highly heterogeneous disease, with locus and allelic heterogeneity both between and within families likely.

Thermodynamic model of electric-field-induced pattern formation in binary dielectric fluids.

An electric-field-induced phase transition and pattern formation in a binary dielectric fluid layer are studied using a coarse-grained free-energy functional. The electrostatic part of the free energy is a nonlinear functional of the dielectric function, which depends in turn on the local colloidal concentration. We determine the phase coexistence curve and find that beyond a critical electric field the system phase separates.

Physical activity participation among persons with disabilities: barriers and facilitators.

Background: The purpose of this study was to identify various barriers and facilitators associated with participation in fitness and recreation programs/facilities among persons with disabilities.

Methods: Focus groups were conducted in ten regions across the United States in 2001 to 2002 with four types of participants: (1) consumers with disabilities, (2) architects, (3) fitness and recreation professionals, and (4) city planners and park district managers. Sessions were tape-recorded and content analyzed; focus group facilitators took notes of identified barriers and facilitators to access.

Missed injury in major trauma patients.

Objectives: To determine the incidence, aetiology and contributing factors to injuries being missed during the primary and secondary surveys in patients with major trauma managed on a general Adult Intensive Care Unit (AICU).

Methods: The records for patients admitted to the AICU following severe injury (defined as injury severity score (ISS) >16) over a 1-year period were reviewed. Diagnostic imaging performed during the resuscitation was reviewed in cases where missed injuries were discovered.

Multicenter linkage study of schizophrenia loci on chromosome 22q.

The hypothesis of the existence of one or more schizophrenia susceptibility loci on chromosome 22q is supported by reports of genetic linkage and association, meta-analyses of linkage, and the observation of elevated risk for psychosis in people with velocardiofacial syndrome, caused by 22q11 microdeletions. We tested this hypothesis by evaluating 10 microsatellite markers spanning 22q in a multicenter sample of 779 pedigrees. We also incorporated age at onset and sex into the analysis as covariates.

A direct role for Fgf but not Wnt in otic placode induction.

Induction of the otic placode, which gives rise to all tissues comprising the inner ear, is a fundamental aspect of vertebrate development. A number of studies indicate that fibroblast growth factor (Fgf), especially Fgf3, is necessary and sufficient for otic induction. However, an alternative model proposes that Fgf must cooperate with Wnt8 to induce otic differentiation.

Hereditary nonpolyposis colorectal carcinoma (HNPCC) and HNPCC-like families: Problems in diagnosis, surveillance, and management.

Background: To the authors' knowledge, hereditary nonpolyposis colorectal carcinoma (HNPCC) is the most commonly occurring hereditary disorder that predisposes to colorectal carcinoma (CRC), accounting for approximately 2-7% of all CRC cases diagnosed in the U.S each year. Its diagnosis is wholly dependent on a meticulously obtained family history of cancer of all anatomic sites, with particular attention to the pattern of cancer distribution within the family.

Organizational capacity and implementation change: a comparative case study of heart health promotion in Ontario public health agencies.

This paper reports the results of a comparative case study that examines factors influencing changes in implementation of heart health promotion activities in Ontario public health units. The study compared two cases that experienced large changes in implementation from 1994 to 1996, but in opposite directions. Multiple data sources were used, with an emphasis on secondary analyses of quantitative surveys of health units and other community agencies, and in-depth interviews of public health staff, collected as part of the Canadian Heart Health Initiative Ontario Project.

Ringing in the new ear: resolution of cell interactions in otic development.

The vertebrate inner ear is a marvel of structural and functional complexity, which is all the more remarkable because it develops from such a simple structure, the otic placode. Analysis of inner ear development has long been a fascination of experimental embryologists, who sought to understand cellular mechanisms of otic placode induction. More recently, however, molecular and genetic approaches have made the inner ear a useful model system for studying a much broader range of basic developmental mechanisms, including cell fate specification and differentiation, axial patterning, epithelial morphogenesis, cytoskeletal dynamics, stem cell biology, neurobiology, physiology, etc.

Carrier risk status changes resulting from mutation testing in hereditary non-polyposis colorectal cancer and hereditary breast-ovarian cancer.

Context: In hereditary cancer syndrome families with an identified cancer associated mutation, mutation testing changes the carrier risk status of the tested person and may change the carrier risk status of relatives.

Objective: This study aimed to describe the change in the distribution of carrier risk status resulting from testing in hereditary breast-ovarian cancer (HBOC) and hereditary non-polyposis colorectal cancer (HNPCC) families.

Design: This was an observational cohort study.

Identification of a high-risk haplotype for the dystrobrevin binding protein 1 (DTNBP1) gene in the Irish study of high-density schizophrenia families.

A recent report showed significant associations between several SNPs in a previously unknown EST cluster with schizophrenia. (1). The cluster was identified as the human dystrobrevin binding protein 1 gene (DTNBP1) by sequence database comparisons and homology with mouse DTNBP1.

FP-TDI SNP scoring by manual and statistical procedures: a study of error rates and types.

For technologies that are commonly used in ordinary laboratories such as fluorescence-polarization detection with template-directed, dye-terminator incorporation (FP-TDI), SNP genotype scoring is usually done manually. Here we study rates of errors and missing genotypes obtained with this procedure. We also introduce three statistical genotype scoring methods to examine whether they form a viable alternative.

Dissemination of heart health promotion in the Ontario Public Health System: 1989-1999.

This paper reports the results of an analysis of the dissemination of community-based heart health promotion strategies. The research draws on diffusion and socio-ecological theories to study the first 10 years of heart health promotion in the public health system in Ontario, Canada. Using case description and interpretive analysis, the study describes developments in five stages of dissemination, and examines the interplay of factors operating in the internal organizational setting and the external environment in order to explain these developments.

Hereditary breast-ovarian cancer at the bedside: role of the medical oncologist.

Purpose: To provide practical considerations for diagnosing, counseling, and managing patients at high risk for hereditary breast cancer.

Design: We have studied 98 extended hereditary breast cancer (HBC)/hereditary breast-ovarian cancer (HBOC) families with BRCA1/2 germline mutations. From these families, 1,315 individuals were counseled and sampled for DNA testing.

Exercise training for African Americans with disabilities residing in difficult social environments.

Objective: To examine the feasibility, efficacy, and safety of a structured 12-week exercise training program for a predominantly African-American group of adults with multiple health conditions who reside in difficult social environments.

Methods: A total of 37 females and 7 males (mean age, 54.1 years) participated in an exercise training regimen 3 days per week for 60 minutes per day (cardiovascular, 30 minutes; strength, 20 minutes; and flexibility, 10 minutes).

An expanded domain of fgf3 expression in the hindbrain of zebrafish valentino mutants results in mis-patterning of the otic vesicle.

The valentino (val) mutation in zebrafish perturbs hindbrain patterning and, as a secondary consequence, also alters development of the inner ear. We have examined the relationship between these defects and expression of fgf3 and fgf8 in the hindbrain. The otic vesicle in val/val mutants is smaller than normal, yet produces nearly twice the normal number of hair cells, and some hair cells are produced ectopically between the anterior and posterior maculae.

A spatial memory task appropriate for electrophysiological recordings.

We developed a novel method for assessing spatial learning that is compatible with the requirements of electrophysiological recording of multiple single neurons. The behavioral task utilized a rectangular track with 8 reward boxes of which a subset contained available food (bait). Errors were scored whenever the rat investigated a non-baited box location (commission), failed to investigate a baited box location (omission), or hesitated in front of a non-baited box location (hesitation).

Facial recognition test in the elderly: norms, reliability and premorbid estimation.

The Facial Recognition Test (Benton, Hamsher, Varney, & Spreen, 1983; Benton, Sivan, Hamsher, Varney, & Spreen, 1994) was examined in an age-, education- and gender-stratified sample of 346 healthy older adults. Internal consistency reliability estimates were.72 for the Long Form (FRLF),.

Neuropsychological tests in the elderly: methods and sample characteristics of a GRECC study.

This report describes the methods and sample characteristics of a neuropsychological study of the elderly conducted by the Geriatric Research, Education and Clinical Center of the Department of Veterans Affairs Medical Center in Minneapolis, Minnesota. The goal of the study was to provide normative data, internal consistency and 1-year reliability estimates, and validated methods of estimating expected performance level. Thirty-one cognitive measures and a demographic questionnaire were administered to an age-, education-, and gender-stratified sample ( N = 349) and a validation sample (N = 70).

No major schizophrenia locus detected on chromosome 1q in a large multicenter sample.

Reports of substantial evidence for genetic linkage of schizophrenia to chromosome 1q were evaluated by genotyping 16 DNA markers across 107 centimorgans of this chromosome in a multicenter sample of 779 informative schizophrenia pedigrees. No significant evidence was observed for such linkage, nor for heterogeneity in allele sharing among the eight individual samples. Separate analyses of European-origin families, recessive models of inheritance, and families with larger numbers of affected cases also failed to produce significant evidence for linkage.