1,721,032 research outputs found
Proteasome modulation in brain: A new target for anti-aging drugs?
No full textProteasomes (including constitutive proteasome, immunoproteasome, and their regulatory complexes) are multicatalytic complexes crucial for cell and body homeostasis and survival, being responsible for a consistent part of protein degradation. In the central nervous system (CNS), the activity of proteasomes affects a variety of crucial brain activities. While proteasome alteration (content and activity) during aging has been studied in several tissues and cellular models, few data are available regarding human CNS, and the identification of an appropriate and reliable model for the role of proteasome in human brain aging is still lacking. In this review, the available data on proteasome and brain aging in rodents, as well as the few data on non human primates, are critically revised. On the whole, the data regarding changes of proteasome activity and content with age are far from being clear, not only due to the heterogeneity of the models (differences between species, among strains of the same species) but also due to the brain areas considered. We paid particular attention to recent data obtained in human brain of non-demented donors and subjects affected by Alzheimer Disease (AD) demented subjects, as well as to new data on non human primate brain. The study of the possible role of proteasomes in brain aging, and the identification of reliable animal models, is pivotal for the development of possible ad hoc therapeutic interventions capable of retarding/counteracting brain aging and age-related brain pathologies. The therapeutic capability and limits of Vitamin E, the possible set up of proteasome modifiers (activators) as well as the effects on proteasomes of other drugs used for AD therapy are discussed within a scenario which deserves more attention and further investigations. © 2007 Bentham Science Publishers Ltd
The Immunological Self: A reappraisal
No full textAmong the most important theories of modern biological thought, the concept of immune self appeared as a tacit assumption in the speculations of cellular pathologists and physiologists in the second half of the Nineteenth century. Thanks to its first conceptualization advanced by Burnet in the 1950's, immune self gained the central stage during the "golden age of immunology" from 1960 to 1980, just to come up with a recent crisis because of its lack of explanatory power of emergent phenomena such as inflammatory and autoimmune diseases. The following discussion of the immune self history, together with a reassessment of recent experimental data, will suggest a further conceptual turn in the immune self theory that we propose to refer to as "Liquid Self"
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Towards a liquid self: How time, geography, and life experiences reshape the biological identity
No full textThe conceptualization of immunological self is amongst the most important theories of modern biology, representing a sort of theoretical guideline for experimental immunologists, in order to understand how host constituents are ignored by the immune system (IS). A consistent advancement in this field has been represented by the danger/damage theory and its subsequent refinements, which at present represents the most comprehensive conceptualization of immunological self. Here, we present the new hypothesis of "liquid self," which integrates and extends the danger/damage theory. The main novelty of the liquid self hypothesis lies in the full integration of the immune response mechanisms into the host body's ecosystems, i.e., in adding the temporal, as well as the geographical/evolutionary and environmental, dimensions, which we suggested to call "immunological biography." Our hypothesis takes into account the important biological changes occurring with time (age) in the IS (including immunosenescence and inflammaging), as well as changes in the organismal context related to nutrition, lifestyle, and geography (populations). We argue that such temporal and geographical dimensions impinge upon, and continuously reshape, the antigenicity of physical entities (molecules, cells, bacteria, viruses), making them switching between "self" and "non-self" states in a dynamical, "liquid" fashion. Particular attention is devoted to oral tolerance and gut microbiota, as well as to a new potential source of unexpected self epitopes produced by proteasome splicing. Finally, our framework allows the set up of a variety of testable predictions, the most straightforward suggesting that the immune responses to defined molecules representing potentials antigens will be quantitatively and qualitatively quite different according to the immuno-biographical background of the host. © 2014 Grignolio, Mishto, Faria, Garagnani, Franceschi and Tieri
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Immunoproteasomes and immunosenescence
No full textAging is a complex process which is accompanied with the decline and the reshaping of different functions of the body. In particular the immune system is characterized, during ageing (immunosenescence) by a remodeling of innate immunity (well preserved, up-regulated) and clonotypical immunity (severely altered) and by the occurrence of a chronic inflammatory process (inflammaging) which are, at least in part, genetically controlled. In this scenario, it can be anticipated that a crucial role is played by age-related structural and functional alterations and modifications of proteasomes and immunoproteasomes, the last being a key component of antigen processing and MHC class I antigen presentation. A variety of experimental data are available, suggesting that proteasomes are affected by age, and that in centenarians they are relatively preserved. On the contrary, few data are available on immunoproteasomes, likely as a consequence of the poverty of suitable cellular models. Lymphoblastoid cell lines from EBV immortalized B cells from old donors is envisaged as a possible model for the study of immunoproteasomes in humans and their changes with age. Thus, basic questions such as those related to possible consequences, for immune responses in infectious diseases and cancer, of age-related alterations of antigen processing and presenting, change with age of self-antigen repertoire, and the genetic basis of immunoprotesome activity and its change with age, remain largely unanswered. © 2003 Elsevier Ireland Ltd. All rights reserved
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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