1,721,129 research outputs found
Intracellular bioinorganic chemistry and cross talk among different - omics
No full textThe description of the cell life needs not only the knowledge of its genome and proteome, but also of the location of the metal ions and their different complex species in the subcellular compartments, that is of metallome. The cross-talk among these players of the omics’ world secures the cellular homeostasis by means of a complex network, the alteration of which may give rise to many diseases. Copper and zinc ions levels regulate protein expression and metal-responsive transcription factors and in many pathologies metal dyshomeostasis induces to aberrant expression of different factors. microRNAs, a class of a small non-coding RNA molecules, act as RNA silencing and post-transcriptional regulators of gene expression contributing also to metal regulatory activity. The aim of the present review is to present how metals dyshomeostasis can be cause of diseases, involving different and specific metal chaperones, metal transporters, metalloproteins, small molecules and metal-sensing transcription factors. Two distinct classes of pathologies, cancer and osteoarthritis, are discussed starting from the metallostasis (metal homeostasis) and turning up to miRNAs regulation. The understanding of post-translational regulation, driven by metal ions sensing, may help to identify more specific targets and drugs to pathologies in which metal ions are involved
Potential biomarkers and novel pharmacological targets in protein aggregation-related neurodegenerative diseases
Full text linkThe aggregation of specific proteins plays a pivotal role in the etiopathogenesis of several neurodegenerative diseases (NDs). β-Amyloid (Aβ) peptide-containing plaques and intraneuronal neurofibrillary tangles composed of hyperphosphorylated protein tau are the two main neuropathological lesions in Alzheimer's disease. Meanwhile, Parkinson's disease is defined by the presence of intraneuronal inclusions (Lewy bodies), in which α-synuclein (α-syn) has been identified as a major protein component. The current literature provides considerable insights into the mechanisms underlying oligomeric-related neurodegeneration, as well as the relationship between protein aggregation and ND, thus facilitating the development of novel putative biomarkers and/or pharmacological targets. Recently, α-syn, tau and Aβ have been shown to interact each other or with other "pathological proteins" to form toxic heteroaggregates. These latest findings are overcoming the concept that each neurodegenerative disease is related to the misfolding of a single specific protein. In this review, potential opportunities and pharmacological approaches targeting α-syn, tau and Aβ and their oligomeric forms are highlighted with examples from recent studies. Protein aggregation as a biomarker of NDs, in both the brain and peripheral fluids, is deeply explored. Finally, the relationship between biomarker establishment and assessment and their use as diagnostics or therapeutic targets are discussed
Brain ageing and neurodegenerative disease: The role of cellular waste management
Full text linkAgeing is defined as a time-dependent functional decline that occurs in most of live organisms. Brain modification during the ageing process has been considered to predispose to neurodegenerative disorders. Despite intensive research, the exact mechanisms accounting for the switch from physiological brain ageing to neurodegeneration remain to be fully elucidated. At a cellular level, brain ageing is characterized by growing inflammation, oxidative stress, increased genomic instability, altered metabolism and the destruction of protein homeostasis, which causes the accumulation of cellular waste. In this respect, the ubiquitin proteasome system and autophagy represent the two main proteolytic systems accountable for misfolded proteins degradation in neurons. Not surprisingly, the impairment of these systems has been reported in ageing and neurodegenerative disorders characterized by inclusions of protein aggregates. Herein, we provide an overview of the molecular mechanisms that regulate ageing and neurodegenerative disorders, in particular those linked to an alteration of protein degradation. Moreover, the current therapeutic and nutritional interventions used to target protein degradation pathways are explored and discussed in the prospective of stalling or even reversing ageing and neurodegenerative processes
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
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
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
Cytokine secretion responsiveness of lymphomonocytes following cortisol cell exposure: Sex differences
Full text linkThe stress hormone cortisol has been recognized as a coordinator of immune response. However, its different ability to modulate the release of inflammatory mediators in males and females has not been clarified yet. Indeed, the dissection of cortisol specific actions may be difficult due to the complex hormonal and physio-pathological individual status. Herein, the release of inflammatory mediators following increasing cortisol concentrations was investigated in an in vitro model of primary human male and female lymphomonocytes. The use of a defined cellular model to assess sex differences in inflammatory cytokine secretion could be useful to exclude the effects of divergent and fluctuating sex hormone levels occurring in vivo. Herein, the cells were challenged with cortisol concentrations resembling the plasma levels achieving in physiological and stressful conditions. The production of cytokines and other molecules involved in inflammatory process was determined. In basal conditions, male cells presented higher levels of some pro-inflammatory molecules (NF-kB and IDO-1 mRNAs, IL-6 and kynurenine) than female cells. Following cortisol exposure, the levels of the pro-inflammatory cytokines, IL-6 and IL-8, were increased in male cells. Conversely, in female cells IL-6 release was unchanged and IL-8 levels were decreased. Anti-inflammatory cytokines, IL-4 and IL-10, did not change in male cells and increased in female cells. Interestingly, kynurenine levels were higher in female cells than in male cells following cortisol stimulus. These results highlighted that cortisol differently affects male and female lymphomonocytes, shifting the cytokine release in favour of a pro-inflammatory pattern in male cells and an anti-inflammatory secretion profile in female cells, opening the way to study the influences of other stressful factors involved in the neurohumoral changes occurring in the response to stress conditions
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