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Biomedical subjects

William S Davidson

Publications and source records attributed to William S Davidson.

28 records · Page 2Linked to original sources

Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport.

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous developmental disorder whose molecular basis is largely unknown. Here, we show that mutations in the Caenorhabditis elegans bbs-7 and bbs-8 genes cause structural and functional defects in cilia. C. elegans BBS proteins localize predominantly at the base of cilia, and like proteins involved in intraflagellar transport (IFT), a process necessary for cilia biogenesis and maintenance, move bidirectionally along the ciliary axoneme. Importantly, we demonstrate that BBS-7 and BBS-8 are required for the normal localization/motility of the IFT proteins OSM-5/Polaris and CHE-11, and to a notably lesser extent, CHE-2. We propose that BBS proteins play important, selective roles in the assembly and/or function of IFT particle components. Our findings also suggest that some of the cardinal and secondary symptoms of BBS, such as obesity, diabetes, cardiomyopathy, and learning defects may result from cilia dysfunction.

Adaptor Proteins, Signal Transducing↗

Comparative genomics identifies a flagellar and basal body proteome that includes the BBS5 human disease gene.

Cilia and flagella are microtubule-based structures nucleated by modified centrioles termed basal bodies. These biochemically complex organelles have more than 250 and 150 polypeptides, respectively. To identify the proteins involved in ciliary and basal body biogenesis and function, we undertook a comparative genomics approach that subtracted the nonflagellated proteome of Arabidopsis from the shared proteome of the ciliated/flagellated organisms Chlamydomonas and human. We identified 688 genes that are present exclusively in organisms with flagella and basal bodies and validated these data through a series of in silico, in vitro, and in vivo studies. We then applied this resource to the study of human ciliation disorders and have identified BBS5, a novel gene for Bardet-Biedl syndrome. We show that this novel protein localizes to basal bodies in mouse and C. elegans, is under the regulatory control of daf-19, and is necessary for the generation of both cilia and flagella.

Animals↗

Development and application of a salmonid EST database and cDNA microarray: data mining and interspecific hybridization characteristics.

We report 80,388 ESTs from 23 Atlantic salmon (Salmo salar) cDNA libraries (61,819 ESTs), 6 rainbow trout (Oncorhynchus mykiss) cDNA libraries (14,544 ESTs), 2 chinook salmon (Oncorhynchus tshawytscha) cDNA libraries (1317 ESTs), 2 sockeye salmon (Oncorhynchus nerka) cDNA libraries (1243 ESTs), and 2 lake whitefish (Coregonus clupeaformis) cDNA libraries (1465 ESTs). The majority of these are 3' sequences, allowing discrimination between paralogs arising from a recent genome duplication in the salmonid lineage. Sequence assembly reveals 28,710 different S. salar, 8981 O. mykiss, 1085 O. tshawytscha, 520 O. nerka, and 1176 C. clupeaformis putative transcripts. We annotate the submitted portion of our EST database by molecular function. Higher- and lower-molecular-weight fractions of libraries are shown to contain distinct gene sets, and higher rates of gene discovery are associated with higher-molecular weight libraries. Pyloric caecum library group annotations indicate this organ may function in redox control and as a barrier against systemic uptake of xenobiotics. A microarray is described, containing 7356 salmonid elements representing 3557 different cDNAs. Analyses of cross-species hybridizations to this cDNA microarray indicate that this resource may be used for studies involving all salmonids.

Animals↗

AJCP as a vehicle for improving community life: an historic-analytic review of the journal's contents.

The current article is an analysis of the research represented in American Journal of Community Psychology (AJCP) from 1993 to 1998, including a comparison to two previously published analytic reviews by Lounsbury et al. (J. W. Lounsbury, D. S. Leader, E. P. Meares, & M. P. Cook, 1980) and Speer et al. (P. Speer, A. Dey, P. Griggs, C. Gibson, B. Lubin, & J. Hughey, 1992), respectively. Observed trends are examined with references to major epistemological frameworks and methods used to define community psychology. Four guiding principles were examined to determine the representation of the epistemological frameworks of the articles published in the journal. The frameworks include social action, human diversity and cultural relativity, person-environmental fit, and methodological procedures. The results document the transition of community psychology from its early beginnings to an independent field conducting research consistent with the values articulated at the Swampscott Conference. This paper also comments on how well, after three decades of publication, the journal has served as a vehicle for improving community life.

Cultural Diversity↗

An empowerment evaluation model for sexual assault programs: empirical evidence of effectiveness.

Using an empowerment evaluation approach, the Sexual Assault and Rape Prevention (SARP) Evaluation Project brought together university researchers, public health evaluators, state funders, and program staff to provide evaluation training and consultation to all state-funded rape prevention and victim services programs in Michigan. In this paper, the specific activities of the SARP project are described, and process and outcome data are presented that address the effectiveness of this empowerment evaluation approach. Based on subjective reports from program staff and objective data obtained from state funders, results suggest that this evaluation model was successful in helping 90% of the prevention programs and 75% of the victim services programs successfully develop and launch program evaluations. One-year follow-up data indicate that 90% of the programs had sustained their evaluation efforts after the formal work of the SARP project had ended.

Crime Victims↗

The social networks of women experiencing domestic violence.

The research literature has demonstrated that battered women living in shelters experience impaired social support. This study examines this phenomenon among battered women living in the community. This study compared a group of pregnant battered women (n = 145) and a group of pregnant nonbattered women (n = 58) in terms of their structural [e.g., total number of supporters, network members in violent relationships with their partners (an index of homophily or nonhomophily) and functional (e.g., emotional)] social support. Four reasons for impaired support in battered women were proposed and examined, including social isolation, failure to disclose abuse, homophily, and low SES. Only homophily was related to impaired support among battered women. In addition, the relationship between structural and functional support and mental health outcomes (e.g., depression, self-esteem) was examined. Criticism, practical support, homophily, and disclosure were all significant predictors of mental health for battered women. Implications for community-based interventions are discussed in the context of current intervention strategies with battered women.

Adult↗

Promoting political empowerment: evaluation of an intervention with university students.

The aim of this research is to examine the effects of an intervention, focusing on the development of political empowerment, with university students. Undergraduates were randomly assigned to one of two conditions (intervention/ control) and were surveyed at two time points: before implementation of the intervention and upon completion of the intervention (or the equivalent two semester period). ANCOVA analyses reveal that individuals who participated in the empowering intervention had increased feelings of political commitment and a decreased sense of political efficacy compared to individuals who were randomly assigned to a waiting list/control group. Finally, limitations of this study are discussed and suggestions for future research are presented.

Adult↗

Clinical and genetic epidemiology of inherited renal disease in Newfoundland.

Clinical and genetic epidemiology of inherited renal disease in Newfoundland. Newfoundland's geography, settlement, and socioeconomic development have produced a population useful for the study of genetic diseases. This review examines the clinical and genetic epidemiologic studies of inherited renal diseases undertaken in this population in the past 15 years. Common founder effects and large families through each generation provided very extensive pedigrees with autosomal-dominant diseases, such as polycystic kidney disease (PKD) and von Hippel-Lindau disease. In the former disease the diagnostic utility of renal ultrasound was determined, as was the prognostic impact of genotype, the role of the renin-angiotensin system in the pre-hypertensive phase, the potential for somatic mutations of the PKD2 gene, or the combination of mutations in the PKD1 and PKD2 genes, in single cells to induce cysts, and the demonstration that human transheterozygotes of PKD1 and -2 are not embryonically lethal. The presence of multiple genetic isolates and the high coefficient of kinship have predisposed to autosomal recessive diseases such as Bardet-Biedl syndrome (BBS), autosomal-recessive PKD, primary hyperoxaluria, and dihydroxyadenine urolithiasis. We have reported the clinical manifestations and natural history of the BBS, with particular emphasis on the fact that renal abnormalities are cardinal manifestations of the disease, the presence of at least six different genotypes, the identity and function of the BBS6 gene, and the presence of three different BBS6 mutations. Because of its relatively homogenous origins and high coefficient of kinship, Newfoundland's population also may be useful for the study of complex diseases such as preeclampsia. Using unbiased ascertainment and strict diagnostic criteria, we have found a significant risk of preeclampsia and non-proteinuric gestational hypertension in sisters of probands with preeclampsia, particularly when probands are defined by severity of preeclampsia, an observation that supports a study to search for susceptibility genes. We conclude that collaborations between clinical epidemiologists and molecular geneticists, using the Newfoundland population, have provided important clinical and mechanistic insights into inherited renal diseases.

Bardet-Biedl Syndrome↗

Assessing the diversity of personal beliefs about addiction: development of the addiction belief inventory.

Previous work in the field of substance use/misuse has suggested that client beliefs about addiction are quite diverse, and may influence the effectiveness of various treatment approaches. This paper presents an Addiction Belief Inventory (ABI) that was developed and evaluated to assess personal beliefs about addiction and substance use problems. The ABI is a 40-item instrument developed using two clinical samples: an alcohol user treatment group (N = 134) and a dual diagnosis treatment group (N = 536). Confirmatory factor analysis revealed seven stable subscales: inability to control, chronic disease, reliance on experts, responsibility for actions, responsibility for recovery, genetic basis, and coping. Multivariate analyses provided preliminary reliability and validational support. The utility of the ABI for clinical and research purposes is discussed, along with suggestions for future research and improvements to the instrument.

Adult↗

Involvement in 12-step programs among persons with dual diagnoses.

Although many people with substance use problems are referred to Alcoholics Anonymous (AA) or Narcotics Anonymous (NA), few studies have examined characteristics of persons who comply with such referrals. In particular, little is known about self-help meeting attendance by persons with dual diagnoses. This study examined rates of AA and NA attendance among 351 persons with dual diagnoses who were treated in a hospital setting. It also explored the relationship between diagnosis and meeting attendance. Ten months after hospitalization, the study participants demonstrated rates of AA or NA attendance that were similar to those of persons who were diagnosed as having substance use disorders without severe mental illness. However, patients with schizophrenia or schizoaffective disorders reported significantly fewer days of AA or NA meeting attendance.

Adult↗