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)

Isolation in the back-country: George Chamier, G.B. Lancaster, Katherine Mansfield, John Mulgan, and Graham Billing -- Outsiders and misfits in fragmented social milieux: William Satchell, Vincent Pyke, John A. Lee, Robin Hyde, Frank Sargeson, and others -- The lonely and the alone in the fiction of Janet Frame -- Maurice Gee and postmodern isolation -- Women, isolation, and history: Fiona Kidman, Noel Hilliard, and Patricia Grace -- Cultural deracination and isolation : Witi Ihimaera, Keri Hulme, and Alan Duff.

In recent years important contributions to the interpretation of the eighth book of Lucan have been made by Professor Postgate , and by Mr.J.D.Duff .The following notes make a further attempt to solve some of the many problems presented by the book.

This essay reviews six different approaches to intellectual property. It and argues that none of these accounts provide an adequate justification of intellectual property laws and policies because (1) there are many different types of intellectual property, and (2) a variety of incommensurable values play a role in the justification of intellectual property. The best approach to intellectual property is to assess and balance competing moral values in light of the particular facts and circumstances.

This book focuses on the mind and its ability to seek answers to unknown or unanswered questions. The theory of educating provides the grounding for using V diagrams by students, educators, researchers, and parents. Teachers make lesson plans using V diagrams and concept maps. They become expert coaches in guiding student performances. Students learn to construct their own knowledge. They change from question-answerers to question-askers. Parents share meaning with their children and their children's teachers and administrators. Administrators monitor programs and (...) are in touch with all participants in schools and universities. Researchers and evaluators can share records of events and facts. With this theory working in the classrooms and laboratories of many practical places of educating plus extending into the world of technology literacy, The Art of Educating with V Diagrams explains how educating works. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Eclecticism and Adolf Meyer’s Functional Understanding of Mental IllnessD. B. Double (bio)KeywordsAdolf Meyer, eclecticism, functionalism, biopsychosocial modelGhaemi’s Commentary and Meyer’s ‘Eclecticism’I am not against humanism. How could anyone be against the humanistic wisdom rooted in the worthy writings of Socrates, Hippocrates, Shakespeare, Cervantes, Osler, and the others listed by Nassir Ghaemi? Psychiatry should recognize the dignity and value of all people. The problem is that it may not always (...) do so, coming from a reductionist paradigm as it so often does.Ghaemi appreciates that Meyer’s compromising attitude meant that he was “unable to inoculate psychiatry from biological dogmatism.” My emphasis is on the challenge of Meyer’s psychobiology to biomedicine. In the same way, Engel’s biopsychosocial model acknowledged the need to neutralize the power of an impersonal and mechanical medicine. Doctors tend to overemphasize physical abnormalities at the expense of dealing with difficult personal issues.At the risk of oversimplification, I am juxtaposing biopsychosocial and biomedical models in psychiatry. Or in other terms, for our modern understanding, I am asserting a neo-Meyerian approach in contrast to neo-Kraepelinianism. Merely restating the Meyerian perspective will not do, because of Meyer’s ‘give and take,’ and his consequent failure to follow through the implication of his position. At least the ethical ramifications of his conceptual framework need to be acknowledged.Neo-Meyerianism also needs to be realized in the context of the reaction to anti-psychiatry. After anti-psychiatry’s attack, our modern understanding of mental illness has tended to be been subsumed into the binary opposition of ‘pro-psychiatry’ and ‘anti-psychiatry.’ But neo-Meyerianism is as much pro-psychiatric as biomedical psychiatry. It is in this sense that biopsychological approaches have been undermined by the biomedical reaction to anti-psychiatry. [End Page 355]I also agree with Ghaemi that there is a way in which the failures of the biopsychosocial model allowed the development of anti-psychiatry. For example, even though Laing quoted favorably from psychologically minded psychiatrists such as Manfred Bleuler, as far as I know he never made any reference to Meyer. There was never a systematic Meyerian theory to which Laing could refer. In fact, Laing wished to move beyond an interpretative understanding to abandon the metaphor of pathology (Double 2006). Perhaps if the biopsychosocial model had been more clearly defined, Laing would not have felt he needed to take this step. Or, at least in doing so, he would have been clearer about where he stood on this issue. When labeling Laing’s views as ‘anti-psychiatry,’ biomedical psychiatry would have had to state more precisely how Laing’s position was anti- rather than pro-psychiatric.My main disagreement with Ghaemi is his view of Meyer as eclectic. Meyer’s willingness to allow ‘anything goes’ in psychiatry meant that he did not oppose or challenge too much the views of those with whom he disagreed. Nonetheless, he did not combine together different sources to create an unintegrated philosophical and conceptual understanding. His theoretical position is internally consistent.Modern American psychiatry studied by participant observation is “of two minds,” in that there is a divided consciousness created between the practices of drug therapy and psychotherapy (Luhrmann 2000). In this sense, it is eclectic because there is no consistent theory that combines the two practice modes. True, psychiatry often claims that the foundation for this mixture is the biopsychosocial model. It asserts that everyday psychiatry is not as purely biomedical as is often maintained because it takes into account psychosocial factors that may precipitate mental disorders. It, therefore, says that it bring together the biological and psychosocial. This compromise avoids the adoption of any one model and was proposed to neutralize the dogmatism engendered by the anti-psychiatry debate (Clare 1980). I agree with Ghaemi that such eclecticism has outlived its usefulness.Where I think Ghaemi is mistaken is that he sees Meyer and Engel as the originators of this eclecticism. I regard the Meyerian approach as more genuinely pragmatic than Ghaemi suggests. Meyer’s dynamic psychology sought an integration of mind and brain as a way of dealing with the philosophical dilemma of the mind–body... (shrink)

On the vedantic philosophy of Śaṅkaracarya.

Purpose. The aim of the article is to clarify the content of the concept of culture as an explication of vitality within the philosophy of life and its further modifications in current problems of contemporary. The analysis performed standing from the point, that contrasting of nature and culture is irrelevant, since culture does not contradict natural determinants and patterns, but rather qualitatively alters them. So, are justified the idea of culture as a phenomenon that exist accordingly and in proportion to (...) nature, need to form its potential and content and not contradict the axioms and values of life. Theoretical basis. In the theoretical field of philosophy of life, the local development of the problem of culture as an explication of vitality produces grounds for analytical and prognostic activity concerning meaningful transformations in a separate historical and social horizon. The fundamental categories of culture: spirit, value, symbol, freedom, justice and harmony receive the requested content and meaning. The idea of the constancy and super-naturality of cultural universals is illusory and dangerous. The consequences of such a "non-cosmological" justification of freedom and will, and the assertion of values, that contradict the logic of life, are the global environmental, economic and social crisis of our time. Originality. The originality of the authors’ thought lies in the interpretation of the essence of culture as an explication of vitality, as a logical and natural extension of life. In this formulation of the problem of culture, the possibility of reconciling the natural, social and value determinants of human life is formed. Theorists of the philosophy of life substantiated the primacy and supremacy of the values of life over the values and meanings of culture. The position of authors position consists in the need to understand culture as an environmentally appropriate and dimensional phenomenon, the content and strategies of which are determined by a single ontology. Conclusions. The analysis let authors understand the voluntarily chaotic element of life. Culture in its philosophical analysis took on a clearer anthropomorphic dimension: the immanent logic of being in substantiating the essence and purpose of man and the value of his being localized the universe of transcendence in the concept of "living world", "inhabited space", "human, too human". Accordingly, the range of cultural evaluations has been polarized: from the approving statement of its vital essence, to the disparaging calls for its reform. The chaotic state of voluntarily acts is transformed into cultural codes and stereotypes by rationalization. The modern global nature of crisis phenomena, both in the worldview, in the social, and in the ecological dimension, requires reformatting the understanding of culture as a continuation of nature, and not its antipode. (shrink)

Psychiatry is increasingly dominated by the reductionist claim that mental illness is caused by neurobiological abnormalities such as chemical imbalances in the brain. Critical psychiatry does not believe that this is the whole story and proposes a more ethical foundation for practice. This book describes an original framework for renewing mental health services in alliance with people with mental health problems. It is an advance over the polarization created by the "anti-psychiatry" of the past.

Most of the discussion in bioethics and health policy concerning social responsibility for health has focused on society’s obligation to provide access to healthcare. While ensuring access to healthcare is an important social responsibility, societies can promote health in many other ways, such as through sanitation, pollution control, food and drug safety, health education, disease surveillance, urban planning and occupational health. Greater attention should be paid to strategies for health promotion other than access to healthcare, such as environmental and public (...) health and health research.Lifestyle plays a major role in most of the illnesses in industrialised nations.1 Six of the 10 leading factors contributing to the global burden of disease are lifestyle related: unsafe sex, high blood pressure, tobacco use, alcohol use, high cholesterol and obesity.2 Lifestyle-related illnesses also contribute to the rising costs of healthcare. Spending on healthcare accounts for about 16% of the gross domestic product in the USA, or US$1.9 trillion.3 Although smoking has declined steadily there since the 1960s, smoking-related medical expenses are still about US$75.5 billion per year.4 Obesity, which has been climbing in the past two decades, accounts for about US$75 billion in healthcare costs there each year.5 Alcoholism and drug addiction in the USA account for annual healthcare costs of about US$22.5 billion and US$12 billion, respectively.6,7 Federal government spending on healthcare relating to HIV/AIDS is over US$13 billion per year.8Given the well-documented relationship between lifestyle, disease burden and healthcare costs, it makes economic and medical sense to hold individuals morally responsible for their health-related choices. While this view has a great deal of intuitive appeal, it also faces numerous objections.9–12 First, holding individuals entirely responsible for their own health conflicts with medicine’s obligation to treat the sick and society’s obligation …. (shrink)