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.     

Deconstructing the pipeline: using efficacy, effectiveness, and cost-benefit data to reduce minority youth incarceration

Investing in effective prevention and early intervention programs will reduce human costs of victimization and also save tax dollars in the short and long terms.     

Auswirkungen von Downsizing-Maßnahmen auf das organisationale Commitment der verbleibenden Mitarbeiter: Ein Vorher-Nachher-Vergleich

This study examines the consequences of downsizing efforts on organizational commitment, job satisfaction and work motivation of the remaining workforce (?survivors“) in a middle-sized telecommunication company. Employees were surveyed five months prior to the downsizing process (n=150) and eleven months thereafter (n=160). The assessment of organizational commitment was based on a questionnaire that was developed by Allen and Meyer (1990) within the scope of their three-components-model which includes affective, continuous and normative commitment. Although layoffs — as one part of the whole downsizing process — were not implemented in the investigated company, but only in a sister enterprise, which is part of the same holding, the affective commitment of employees towards their corporation dropped. On the other hand, the normative and the balanced commitment remained constant. Moreover, every second survivor showed reduced job satisfaction and work motivation. It should be noted that although the results of reorganisation and restructuring did not directly affect the employees of the investigated company, the emotional linkage between employees and employer was affected in a negative way. Additional findings from qualitative interviews suggest that restructuring was perceived to cause a crack in the prevailing corporate culture and the psychological contract. In addition, a deterioration of work conditions through work overload resulted.     

Germline genomes--a biological fountain of youth?

The fusion of male- and female-derived gametes initiates the phenomenal process of producing a highly complex mammalian organism. Successful reproduction is so important that mammals invoke a battery of protective mechanisms for the germ cell lineages that function to maximize genetic integrity while still allowing genetic diversity and adaptation. Protective mechanisms likely include, but are not limited to, robust DNA repair to safeguard genetic integrity and apoptosis to remove cells with intolerable levels of DNA damage. Analyses of spontaneous mutant frequencies are generally consistent with germline DNA being stringently maintained relative to somatic tissues. Despite the rigorous protection afforded germ cells, genetic integrity is observed to decline with increased maternal and paternal age. It is not yet clear whether cells in the germ line truly age or whether other processes decline or become dysfunctional with age. For example, in a younger animal, the differentiation and/or utilization of germ cells with lower genetic integrity might be disallowed, whereas in an older animal, such cells might slip past these quality-control mechanisms.     

Why Do They Start It? Explaining Reported Early-Teen Sexual Activity

This paper seeks an account of why young teens initiate consensual sexual activity. It does so by constructing statistical models aimed at distinguishing those who report having initiated sexual activity from those who have not in four samples of eighth graders from an Upstate New York county. Theoretical selection of the model variables is guided by insights from problem syndrome, control and differential association theories. From our findings we conclude the following: (1) Risk behaviors foreseen by the problem syndrome approach, including having used marijuana and having been drunk, are significant, powerful predictors of early-teen sexual activity. (2) The social setting of consensual sexual activity differs by sex at the eighth grade level. For example, having a boyfriend is a more consistent, powerful predictor variable for girls than is having a girlfriend for boys and there is evidence to support the hypothesis that boys initiate sexual activity in the context of status-seeking while girls are more likely to do so as a way of attaining approval. (3) Our findings do not give clear primacy to parents or peers as an influence on early-teen consensual sexual activity. Both control theory, usually associated with parental-influence variables, and differential association theory, usually associated with peer-influence variables, receive support. (4) The results of the research spanning a 2-year period of intensive community antiteen-pregnancy efforts by a Zero Adolescent Pregnancy (ZAP) campaign are consistent with the conclusion that such a multifaceted approach might help lower early-teen initiation of sexual activity.     

DO WE REALLY UNDERSTAND? AN EXPERIENTIAL EXERCISE FOR TRAINING FAMILY THERAPISTS

This paper presents an experiential exercise for training beginning marriage and family therapists, as well as several adaptations of the format. The basic exercise consists of role playing a therapy session in which the people playing the clients speak a language that is not understood by the therapist-in-training. Although the therapist cannot understand the clients, the clients can understand the therapist. This exercise assists students to become more cognizant of the need to be cautious and curious in the cocreation of meaning in therapy. In addition, this exercise builds confidence and clinical skills, such as learning about nonverbal communication while observing process.     

A follow-up study of posttraumatic stress disorder, anxiety, and depression in Australian victims of domestic violence

Although posttraumatic stress disorder (PTSD), anxiety, and depression are acknowledged consequences of domestic violence, little information is available on the course of recovery over time and factors that may mediate positive outcome. Fifty-nine women were assessed for the presence of PTSD and levels of anxiety and depression at time of shelter residence and again one year later. Results at follow-up indicated a significant reduction in the incidence of PTSD, although a substantial number of women continued to report a range of posttrauma symptoms. There were also significant reductions in the levels of anxiety and depression over the 12-month period. Findings indicated the particular importance of safety and the presence of social support as prerequisites for recovery.     

Including siblings in the treatment of child sexual abuse

Siblings are often not included in treatment programs for children who have been sexually abused. This article describes the necessity of including siblings in the treatment of victims of child sexual abuse. Including siblings in treatment permits families to realize the maximum benefits of therapy for the victim as well as each family member. Theoretical and practical reasons to include siblings in treatment are discussed (i.e., preventing future abuse, providing support for siblings, teaching siblings to refrain from victim-blaming). Case examples using a particular intervention approach at The Family Learning Program and results of client satisfaction surveys are described.     

Neighborhood disadvantage, stress, and drug use among adults

This paper explores the relationships among neighborhood disadvantage, stress, and the likelihood of drug use in a sample of adults (N = 1,101). Using the 1995 Detroit Area Study in conjunction with tract-level data from the 1990 census, we find a positive relationship between neighborhood disadvantage and drug use, and this relationship remains statistically significant net of controls for individual-level socioeconomic status. Neighborhood disadvantage is moderately associated with drug related behaviors, indirectly through increased social stressors and higher levels of psychological distress among residents of disadvantaged neighborhoods. A residual effect of neighborhood disadvantage remains, net of a large number of socially relevant controls. Finally, results from interactive models suggest that the relationship between neighborhood disadvantage and drug use is most pronounced among individuals with lower incomes.     

Alternative solutions to the problem of selection bias in an analysis of federal residential drug treatment programs

In an evaluation of prison-based residential drug treatment programs, the authors use three different regression-based approaches to estimating treatment effects. Two of the approaches, the instrumental variable and the Heckman approach, attempt to minimize selection bias as an explanation for treatment outcomes. Estimates from these approaches are compared with estimates from a regression in which treatment is represented by a dummy variable. The article discusses the advantage of using more than one method to increase confidence in findings when possible selection bias is a concern. Three-year outcome data for 2,315 federal inmates are used in analyses where the authors separately examine criminal recidivism and relapse to drug use for men and women. Statistical tests lead the authors to conclude that treatment reduces criminal recidivism and relapse to drug use. The treatment effect was largest when the inference was based on the Heckman approach, somewhat smaller when based on the instrumental variable approach, and smallest when based on the traditional dummy variable approach. Treatment effects for females were not statistically significant.