Biochemical detection of Aβ isoforms: implications for pathogenesis, diagnosis, and treatment of Alzheimer’s disease

AbstractPrior to the identification of the various abnormal proteins deposited as fibrillar aggregates in the Alzheimer’s disease (AD) brain, there was tremendous controversy over the importance of the various lesions with respect to primacy in the pathology of AD. Nevertheless, based on analogy to systemic amyloidosis, many investigators believed that the amyloid deposits in AD played a causal role and that characterization of these deposits would hold the key to understanding this complex disease. Indeed, in retrospect, it was the initial biochemical purifications of the ∼4 kDa amyloid β-peptide (Aβ) from amyloid deposits in the mid 1980s that launched a new era of AD research (Glenner and Wong, Biochem. Biophys. Res. Commun. 122 (1984) 1121–1135; Wong et al., Proc. Natl. Acad Sci. USA 82 (1985) 8729–8732; and Masters et al., Proc. Natl. Acad Sci. USA 82 (1985) 4245–4249). Subsequent studies of the biology of Aβ together with genetic studies of AD have all supported the hypothesis that altered Aβ metabolism leading to aggregation plays a causal role in AD. Although there remains controversy as to whether Aβ deposited as classic amyloid or a smaller, aggregated, form causes AD, the relevance of studying the amyloid deposits has certainly been proven. Despite the significant advances in our understanding of the role of Aβ in AD pathogenesis, many important aspects of Aβ biology remain a mystery. This review will highlight those aspects of Aβ biology that have led to our increased understanding of the pathogenesis of AD as well as areas which warrant additional study

Time-dependent appearance of myofibroblasts in granulation tissue of human skin wounds

Human skin wounds (66) inflicted between 20 h and 7 months prior to biopsy were studied. In order to identify the type of cellular differentiation of the fibroblastic cells in the granulation tissue, alpha-smooth muscle actin and desmin were immunohistochemically localized. The value of any presumed time-dependent appearance and/or disappearance of positively stained cells was tested for the estimation of wound age. In skin specimens with a wound age less than 5 days (n =15) no typical granulation tissue had developed and no alpha-actin-positive myofibroblasts could be detected. The first appearance of positively reacting myofibroblasts was noted in a 5-day-old wound. In 57% of the lesions with a wound age between 5 and 31 days (25 out of 44 cases) typical granulation tissue formation was present and myofibroblasts with positive reaction for alpha-smooth muscle actin could be identified. Numerous positively reacting cells could generally be found in wounds aged between 16 and 31 days, but also in wounds less than 16 days old. In 29% of the cases with a wound age of more than 31 days (2 out of 7 cases) alpha-sma-positive myofibroblasts also occured. Fibroblastic cells positive for desmin could not be seen at all in our series. Our results demonstrate the appearance of alpha-sma-positive myofibroblasts with the initial formation of typical granulation tissue in human skin lesions as early as approximately 5 days after wounding. In contrast to recent experimental results these cells remained detectable in wounds aged more than 2 months in some cases. The immunohistochemical detection of actin-positive cells, therefore, demonstrates whether an unknown skin wound is aged approximately 5 days or more. Even though a time-dependent decrease of myofibroblasts in human granulation tissue after 31 days in human wounds seems probable, the extended presence (up to about 2 months) of these cells allows no further exact age determination of older wounds

Strength in diversity: enhancing learning in vocationally-orientated, master's level courses

Postgraduate education in geography, especially at the Master’s level, is undergoing significant changes in the developed world. There is an expansion of vocationally-oriented degree programmes, increasing recruitment of international students, integration of work place skills, and the engagement of non-traditional postgraduate students as departments respond to policies for a more ‘inclusive’ higher education. This paper sets the context by outlining some programmatic changes in selected countries (Australia, the UK, and the USA). We briefly reflect on how postgraduate ‘bars’ or ‘levels’ are defined and explore in detail what ‘diversity’ or ‘heterogeneity’ means in these new postgraduate settings. The paper then explores some examples of practice drawn from our own experiences, whilst recognising that relevance will vary in other contexts. Finally we consider how diversity can be harnessed as a strength that has potential to enhance taught elements of contemporary postgraduate education in and beyond the discipline

On the joint production of research and training

Universities and research institutions have the responsibility to produce science and to provide training to new generations of researchers. In this paper, we propose a model to analyze the determinants of a senior scientist’s decisions about allocating time between these tasks. The results of this decision depend upon the characteristics of the research project, the senior scientist’s concern for training and the expected innate ability of the junior scientist involved. We analyze the role that a regulator can play in defining both the value of scientific projects and the future population of independent scientists.info:eu-repo/semantics/publishedVersio

The Eyes Have It: Sex and Sexual Orientation Differences in Pupil Dilation Patterns

Recent research suggests profound sex and sexual orientation differences in sexual response. These results, however, are based on measures of genital arousal, which have potential limitations such as volunteer bias and differential measures for the sexes. The present study introduces a measure less affected by these limitations. We assessed the pupil dilation of 325 men and women of various sexual orientations to male and female erotic stimuli. Results supported hypotheses. In general, self-reported sexual orientation corresponded with pupil dilation to men and women. Among men, substantial dilation to both sexes was most common in bisexual-identified men. In contrast, among women, substantial dilation to both sexes was most common in heterosexual-identified women. Possible reasons for these differences are discussed. Because the measure of pupil dilation is less invasive than previous measures of sexual response, it allows for studying diverse age and cultural populations, usually not included in sexuality research