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)

The Database on Ethics Related Legislation and Guidelines was launched in March 2007 as the fourth database of the UNESCO Global Ethics Observatory system of databases in ethics of science and technology. The database offers a collection of legal instruments searchable by region, country, bioethical themes, legal categories and applicability to specific articles of the UNESCO Universal Declaration on Bioethics and Human Rights and International Declaration on Human Genetic Data. This paper discusses the background and rationale for the database and (...) its role as a consultative and comparative resource hub for the study of ethics related legal instruments across the world, with the purpose of informing and inspiring relevant stakeholders on the implementation of the principles contained within the UNESCO declarations on bioethics. (shrink)

Confusion concerning the issue of universality of colour categorization would greatly diminish if context regains its fundamental status in psychological research and we give up on the reductionist notion that biological universality implies behavioral universality.

This collection of classic works from the mid-nineteenth through mid-twentieth centuries was originally published under the auspices of the Royal Asiastic Society. Spanning over 100 years in oriental scholarship, primary texts include work by Frederic Rosen, W.F. Thompson, C. Edward Sachau, R.A. Nicholson, W.H.T. Gairdner, W.M. Miller, James Robson, and many others.

The prospect of using cell-based interventions to treat neurological conditions raises several important ethical and policy questions. In this target article, we focus on issues related to the unique constellation of traits that characterize CBIs targeted at the central nervous system. In particular, there is at least a theoretical prospect that these cells will alter the recipients' cognition, mood, and behavior—brain functions that are central to our concept of the self. The potential for such changes, although perhaps remote, is cause (...) for concern and careful ethical analysis. Both to enable better informed consent in the future and as an end in itself, we argue that early human trials of CBIs for neurological conditions must monitor subjects for changes in cognition, mood, and behavior; further, we recommend concrete steps for that monitoring. Such steps will help better characterize the potential risks and benefits of CBIs as they are tested and potentially used for treatment. (shrink)

Philosophy of history is not a subject which has hitherto attracted much attention in this country. Preoccupation with the methods and achievements of the natural sciences, and distaste for the sort of rationale of history as a whole which Hegel and others offered under the title in the early nineteenth century, have served to make most British philosophers accord its problems only the most casual recognition. It is therefore all the more interesting to find an English writer of unusual powers (...) both of argument and expression, who was himself an historian of distinction in his special field, devoting a large part of his philosophical thinking to the problems of historical knowledge and their wider implications. Unfortunately, R. G. Collingwood was not able to begin the major work on philosophy of history, to writing which, as we are told in the introduction to the present book, he had looked forward for twenty-five years, until his powers were seriously affected by bad health, and he did not live to complete it. But though the full results of his thinking on the subject are lost, we are now able, thanks to the skilful work of his friend Professor T. M. Knox, to study what is in effect an extensive interim report on it. Professor Knox has produced The Idea of History largely on the basis of lectures which Collingwood prepared in 1936, supplemented by two essays already published which date from the same period and a certain amount of material from the unfinished Principles of History written in 1939. (shrink)

The question I want to discuss is that of the sense and respects in which morality is strictly a matter for the individual. To hear some people talk you would think that it is wholly so. Not only do I have to make my own moral decisions; I have in a way to make them on my own terms, in so far as the rules I take to govern my actions are rules I have freely accepted, or at the least (...) not positively repudiated. In law I can be bound by statutes which I regard as abhorrent or even of whose content I am ignorant ; that a similar situation should obtain in morals is commonly treated as absurd. If I see nothing wrong with a certain practice, such as premarital sex or drug-taking, I can’t be brought morally to book for indulging in it. Morals is not solely a matter of personal taste, for the nature of moral judgment is such that the moral agent legislates not just for himself but for all who are similarly situated; equally, however, it is not something which can be externally enforced. There are no objective moral principles, plain for all to see, against which to measure moral error, and though there is fairly widespread agreement among the respectable that some forms of conduct are morally admirable and others morally deplorable, we are under no obligation to respect these “conventions.” A man’s only true obligation here is to follow his conscience and thus do what he takes to be right, in the light of the best information about the situation he can get. (shrink)

The objectives of this study were to develop a high-density chromosome bin map of homoeologous group 7 in hexaploid wheat, to identify gene distribution in these chromosomes, and to perform comparative studies of wheat with rice and barley. We mapped 2148 loci from 919 EST clones onto group 7 chromosomes of wheat. In the majority of cases the numbers of loci were significantly lower in the centromeric regions and tended to increase in the distal regions. The level of duplicated loci (...) in this group was 24% with most of these loci being localized toward the distal regions. One hundred nineteen EST probes that hybridized to three fragments and mapped to the three group 7 chromosomes were designated landmark probes and were used to construct a consensus homoeologous group 7 map. An additional 49 probes that mapped to 7AS, 7DS, and the ancestral translocated segment involving 7BS also were designated landmarks. Landmark probe orders and comparative maps of wheat, rice, and barley were produced on the basis of corresponding rice BAC/PAC and genetic markers that mapped on chromosomes 6 and 8 of rice. Identification of landmark ESTs and development of consensus maps may provide a framework of conserved coding regions predating the evolution of wheat genomes. (shrink)

A total of 1918 loci, detected by the hybridization of 938 expressed sequence tag unigenes from 26 Triticeae cDNA libraries, were mapped to wheat homoeologous group 4 chromosomes using a set of deletion, ditelosomic, and nulli-tetrasomic lines. The 1918 EST loci were not distributed uniformly among the three group 4 chromosomes; 41, 28, and 31% mapped to chromosomes 4A, 4B, and 4D, respectively. This pattern is in contrast to the cumulative results of EST mapping in all homoeologous groups, as reported (...) elsewhere, that found the highest proportion of loci mapped to the B genome. Sixty-five percent of these 1918 loci mapped to the long arms of homoeologous group 4 chromosomes, while 35% mapped to the short arms. The distal regions of chromosome arms showed higher numbers of loci than the proximal regions, with the exception of 4DL. This study confirmed the complex structure of chromosome 4A that contains two reciprocal translocations and two inversions, previously identified. An additional inversion in the centromeric region of 4A was revealed. A consensus map for homoeologous group 4 was developed from 119 ESTs unique to group 4. Forty-nine percent of these ESTs were found to be homoologous to sequences on rice chromosome 3, 12% had matches with sequences on other rice chromosomes, and 39% had no matches with rice sequences at all. Limited homology was found between wheat ESTs on homoeologous group 4 and the Arabidopsis genome. Forty-two percent of the homoeologous group 4 ESTs could be classified into functional categories on the basis of blastX searches against all protein databases. (shrink)