Cyclin-dependent kinase 5 has been implicated in Alzheimer's disease pathogenesis. Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A p25/cdk5 responsive region containing multiple sites for signal transducer and activator of transcription was identified in the BACE1 promoter. STAT3 interacts with the BACE1 promoter, and p25-overexpressing mice had elevated levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels. Furthermore, mice with a (...) targeted mutation in the STAT3 cdk5 responsive site had lower levels of BACE1. Increased BACE levels in p25 overexpressing mice correlated with enhanced amyloidogenic processing that could be reversed by a cdk5 inhibitor. These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis. (shrink)

Joachim Schulte’s introduction provides a distinctive and masterful account of the full range of Wittgenstein’s thought. It is concise but not compressed, substantive but not overloaded with developmental or technical detail, informed by the latest scholarship but not pedantic. Beginners will find it accessible and seasoned students of Wittgenstein will appreciate it for the illuminating overview it provides.

L'A. soutient, contre Germain Grisez, Joseph Boyle, John Finnis et William May, que le contrôle naturel des naissances pratiqué avec une intention mauvaise n'est pas contraception. Il montre que les auteurs identifient de façon incorrecte la fin prochaine de la contraception comme choix qu'il n'y ait pas d'enfant, alors que la fin prochaine véritable est d'empêcher un enfant de venir au monde . Ainsi donc, puisque en NFP un couple ne cherche pas à empêcher la venue au monde d'un enfant, (...) NFP n'implique pas d'action contraceptive. L'A. soutient aussi qu'identifier la fin prochaine comme choix qu'il n'y ait pas d'enfant ne spécifie pas de façon adéquate une classe homogène d'actes objectifs, bien que cela spécifie une classe homogène d'actes moraux. (shrink)

Objectives: To study the attitudes of both medical and non-medical students towards the do-not-resuscitate decision in a university in Hong Kong, and the factors affecting their attitudes.Methods: A questionnaire-based survey conducted in the campus of a university in Hong Kong. Preferences and priorities of participants on cardiopulmonary resuscitation in various situations and case scenarios, experience of death and dying, prior knowledge of DNR and basic demographic data were evaluated.Results: A total of 766 students participated in the study. There were statistically (...) significant differences in their DNR decisions in various situations between medical and non-medical students, clinical and preclinical students, and between students who had previously experienced death and dying and those who had not. A prior knowledge of DNR significantly affected DNR decision, although 66.4% of non-medical students and 18.7% of medical students had never heard of DNR. 74% of participants from both medical and non-medical fields considered the patient’s own wish as the most important factor that the healthcare team should consider when making DNR decisions. Family wishes might not be decisive on the choice of DNR.Conclusions: Students in medical and non-medical fields held different views on DNR. A majority of participants considered the patient’s own wish as most important in DNR decisions. Family wishes were considered less important than the patient’s own wishes. (shrink)