Metabolism of diphenylamine in the rat and rabbit

Zusammenfassung Nach oraler Verabreichung von Diphenylamin wurde das Kaliumsalz des 4-Oxydiphenylaminsulfatesters aus dem Harn des Kaninchens isoliert. Die enzymatische Hydrolyse des Kaninchenharns ergab kleine Mengen von 2-Oxydiphenylamin, die mit Hilfe von Dünnschicht-Chromatographie identifiziert wurden. Bei der Ratte gelang nach intraperitonealer Verabreichung von Diphenylamin bei enzymatischer und saurer Hydrolyse des Harns der chromatographische Nachweis des 4-Oxydiphenylamins als Hauptprodukt der Umwandlung.

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This work forms part of a programme supported by Grant EF.258 of the National Institute of Health, U.S. Public Health Service, the National Health and Medical Research Council of Australia and the Council of the Australian Food Technologists Association.     

Charge-transfer complexations among biochemically reactive compounds

Zusammenfassung Bei vielen biochemischen Stoffen wird die mit Ladungstransfer verbundene Komplexbildung durch Veränderungen im gemessenen Absorptionsspektrum angezeigt. Die mögliche Bedeutung einer solchen Komplexbildung, insbesondere bei Wasserstoff-und Elektronentransport innerhalb biologischer Systeme, wird diskutiert.

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This work was supported by Public Health Service Grants HE-04138 and AM-04585.     

Cognitive change and the APOE epsilon 4 allele

There is a marked variation in whether people retain sufficient cognitive function to maintain their quality of life and independence in old age, even among those without dementia, so it would be valuable to identify the determinants of normal age-related cognitive change. We have retested non-demented 80-year-olds who were participants in the Scottish Mental Survey of 1932, and find that the variation in their non-pathological cognitive change from age 11 to 80 is related to their apolipoprotein E (APOE) genotype. This effect of the APOE epsilon 4 allele on normal cognitive ageing may be mediated by a mechanism that is at least partly independent of its predisposing effect towards Alzheimer's disease.     

Toward a Holistic View of Staff Development of Regional Tutorial Staff at the Open University

This paper presents a personal account of the theory and practice of staff development of Open University (OU) tutorial staff, based on nearly 30 years' experience, during which I have consciously reflected on my work, continually building on what has seemed important. It results from an extensive process of reflection in which I have tried to capture an understanding of what I do, with the aid of systems models. Some of the basic assumptions and systems models I present have more or less stood the test of time for a number of years; others are the result of my latest reflections. I show how I have used systems concepts and methods to form a coherent, holistic framework for developing tutorial staff in the East Anglian Region of the OU. Two aspects of this work are emphasized: first, the role that staff development can play in improving tutors' basic skills and understanding of their role; second, how the quality of their work is managed through using feedback and the notions of single- and double-loop learning. An important feature of this work has been the setting-up of communities of practice which enable learning by individual tutors to be shared with their peers and transformed into organizational learning for general use. Starting with some basic assumptions about staff development, a number of systemic models are presented which fit into a coherent framework, linking theory to practice and embodying Rene Dubos' (1972) well-known dictum to "Think globally, act locally."     

Identification of the gene that, when mutated, causes the human obesity syndrome BBS4

Bardet-Biedl syndrome (BBS, MIM 209900) is a heterogeneous autosomal recessive disorder characterized by obesity, pigmentary retinopathy, polydactyly, renal malformations, mental retardation, and hypogenitalism. The disorder is also associated with diabetes mellitus, hypertension, and congenital heart disease. Six distinct BBS loci map to 11q13 (BBS1), 16q21 (BBS2), 3p13-p12 (BBS3), 15q22.3-q23 (BBS4), 2q31 (BBS5), and 20p12 (BBS6). Although BBS is rare in the general population (<1/100,000), there is considerable interest in identifying the genes causing BBS because components of the phenotype, such as obesity and diabetes, are common. We and others have demonstrated that BBS6 is caused by mutations in the gene MKKS (refs. 12,13), mutation of which also causes McKusick-Kaufman syndrome (hydrometrocolpos, post-axial polydactyly, and congenital heart defects). MKKS has sequence homology to the alpha subunit of a prokaryotic chaperonin in the thermosome Thermoplasma acidophilum. We recently identified a novel gene that causes BBS2. The BBS2 protein has no significant similarity to other chaperonins or known proteins. Here we report the positional cloning and identification of mutations in BBS patients in a novel gene designated BBS4.     

The mouse Ames waltzer hearing-loss mutant is caused by mutation of Pcdh15, a novel protocadherin gene

The neuroepithelia of the inner ear contain hair cells that function as mechanoreceptors to transduce sound and motion signals. Mutations affecting these neuroepithelia cause deafness and vestibular dysfuction in humans. Ames waltzer (av) is a recessive mutation found in mice that causes deafness and a balance disorder associated with the degeneration of inner ear neuroepithelia. Here we report that the gene that harbours the av mutation encodes a novel protocadherin. Cochlear hair cells in the av mutants show abnormal stereocilia by 10 days after birth (P10). This is the first evidence for the requirement of a protocadherin for normal function of the mammalian inner ear.