The Werner syndrome helicase-nuclease--one protein, many mysteries

Werner syndrome (WS) is an autosomal recessive condition characterized by an early onset of age-related symptoms that include ocular cataracts, premature graying and loss of hair, arteriosclerosis and atherosclerosis, diabetes mellitus, osteoporosis, and a high incidence of some types of cancers. A major motivation for the study of WS is the expectation that elucidation of its underlying mechanisms will illuminate the basis for "normal" aging. In 1996, the gene responsible for the syndrome was positionally cloned. This advance launched an explosion of experiments aimed at unraveling the molecular mechanisms that lead to the WS phenotype. Soon thereafter, its protein product, WRN, was expressed, purified, and identified as a DNA helicase-exonuclease, a bifunctional enzyme that both unwinds DNA helices and cleaves nucleotides one at a time from the end of the DNA. WRN was shown to interact physically and functionally with several DNA-processing proteins, and WRN transgenic and null mutant mouse strains were generated and described. The substantial number of excellent reviews on WRN and WS that were published in the past 2 years (1-7) reflects the rapid pace of advances made in the field. Unlike those comprehensive articles, this review focuses on the biochemistry of the WRN protein and some aspects of its cell biology. Also considered are the putative functions of WRN in normal cells and the consequences of the loss of these functions in WS.     

Quality of Life Indexes for National Policy: Review and Agenda for Research

A number of governments and public policy institutes have developed Quality of Life Indexes – statistics that attempt to measure the quality of life for entire states or regions. We develop 14 criteria for determining the validity and usefulness of such QOL indexes to public policy. We then review 22 of the most-used QOL indexes from around the world. We conclude that many of the indexes are successful in that they are reliable, have established time series measures, and can be disaggregated to study subpopulations. However, many fall short in four areas: (1) indexes vary greatly in their coverage and definitions of domains of QOL, (2) none of the indexes distinguish among the concepts of input, throughput, and output that are used by public policy analysts, (3) they fail to show how QOL outputs are sensitive to public policy inputs, and (4) none have examined convergent validity against each other. We conclude that many of these indexes are potentially very useful for public policy and recommend research to further improve them.     

Widowhood and spirituality: coping responses to bereavement

Nearly half of women age 65 or older are widows and nearly 70% of these women live alone. Because older women are three times more likely than their male counterparts to be widowed, widowhood has been labeled a primarily female phenomenon. This review article has two aims: (a) to discuss the impact of widowhood on the lives of older women and (b) to discuss how religion and spirituality may be used as coping methods for conjugal loss. After reviewing the literature the authors conclude that older women use religious coping as well as religious and spiritual beliefs and behaviors to facilitate positive adjustment to the loss of a spouse.     

Heterosocial competence of rapists and child molesters: a meta-analysis

A meta-analysis of 119 effect sizes from 14 papers examined the heterosocial competence of sex offenders. Rapists had significantly lower heterosocial competence than non-sex-offenders, but this effect was relatively small. Rapists in prison differed from non-sex-offenders who were not in prison; however, they did not differ from non-sex-offending prisoners. When unreliable measures were excluded from the analysis, nonincarcerated students and other volunteers who reported committing rape did not differ from nonincarcerated non-sex-offenders. The difference in heterosocial competence between child molesters and non-sex-offenders was significantly larger than the difference between rapists and non-sex-offenders. Also, child molesters had significantly less heterosocial competence than rapists. Findings clarify the relationship between heterosocial competence, rape, and child sexual abuse. Implications for the research and treatment of sex offenders are discussed.     

Think they're drunk? Alcohol servers and the identification of intoxication

Despite alcohol server training programs and legal liability aimed at controlling intoxication, server intervention appears to be rare. Given the difficulty in assessing intoxication, it can be assumed that improvement in assessment skills would increase the likelihood of intervention. Unfortunately, little is known regarding practices servers use to identify intoxication. In order to build a more informed base for policy formation and server training, the focus of this inquiry was to examine practices used by servers to assess intoxication. The analysis was based upon questionnaires mailed to a random probability sample of licensed servers from one state (N = 822). Indicators found to be most important were examined in relation to a variety of occupational characteristics. Implications for training curricula, policy formation, and future research are discussed.     

Differences in African American and White college students' drinking behaviors: consequences, harm reduction strategies, and health information sources

The authors explored the differences between African American and White college students' drinking behaviors and their attitudes toward consequences, harm-reduction strategies, and health information sources. They collected data from a randomly selected sample of 1,110 students in a large public university to examine the effects of a high-risk drinking prevention intervention. In the current analysis, they compared African American and White students on indicators of high-risk drinking, drinking consequences, harm-reduction strategies, the sources that students typically used for health information, and the believability of those sources. The African American students scored lower on drinking measures than the White students did, reported fewer negative consequences, and more regularly employed drinking-reduction strategies, with one exception--choosing a designated driver. Both African and White respondents reported that their parents were their most frequent and usual sources of health-related information and said that parents and health professionals were the most credible sources.     

Cost-effectiveness of a prework screening program for the University of Illinois at Chicago physical plant

A post-offer screening program jointly developed by the Occupational and Physical Therapy Departments (University of Illinois at Chicago) was first implemented in March 1998. A total of 712 screens were completed from 3-01-98 through 2-28-01. A quasi-experimental design was utilized to analyze changes in Workers' Compensation costs between the three-year period prior to, and the three-year period following program inception. Additionally, injury rates and mean cost per injury were compared between injuries sustained between 3-98 and 3-01 which were incurred by workers who had passed screening and those that had not been screened. Finally, the tabulated cost per screen and reduction in Workers' Compensation costs allowed derivation of a dollar spent/ dollar saved ratio. Dramatic declines in number of injuries, total costs and mean cost per case occurred in the three-year period following program inception. Mean cost per case also dramatically declined comparing injured workers who had passed screening versus those who had never been screened. Cost savings were over US dollars 18 per dollar spent on the program. While a number of mitigating variables may have accounted for some of the profound effects noted, decrease in average cost per case (indicating possible reduction in severity of injury) was consistent with existing literature.     

Gamma-secretase--intramembrane protease with a complex

Gamma-secretase catalyzes intramembrane proteolysis of the amyloid beta protein precursor, a process closely linked to the development of Alzheimer's disease. This protease also cleaves the transmembrane domain of the Notch receptor as part of a signaling pathway that is essential for proper embryonic development. Recent findings suggest that gamma-secretase is a complex of at least four integral membrane proteins: presenilin, nicastrin, Aph-1, and Pen-2. Assembly of these four components apparently leads to autocleavage of presenilin into two subunits that together compose the intramembranous active site of gamma-secretase. Understanding the mechanism of this unusual enzyme is important, as it is both a key therapeutic target and a founding member of a newly discovered class of intramembrane-cleaving proteases.