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Counteracting sarcopenia: The role of IGF-1 isoforms
Full text linkSarcopenia, the age-related loss of muscle mass and strength, represents one of the main causes of impaired physical performance and reduced mobility. Thus, understanding the pathogenetic mechanisms of muscle wasting associated with aging has been the objective of numerous studies and represents an important first step for the development of therapeutic approaches [1,2].
Among growth factors, the insulin-like growth factor-1 (IGF-1) have been implicated in the control of skeletal muscle growth, differentiation, and regeneration and has emerged as a growth factor with a remarkably wide range of actions and a tremendous potential as a therapeutic factor in attenuating the atrophy and frailty associated with muscle ageing and diseases [3,4]. In the adult mammals, IGF-1 is principally synthesized in the liver, acting as a systemic growth factor; however, it is also produced in extrahepatic tissues, including skeletal muscle, where it mainly plays an autocrine/paracrine role. The IGF-1 protein is produced by different pre-pro-peptides, whereas two different promoters and differential splicing of the IGF-1 gene create several IGF-1 isoforms, which differ in the N-terminal signal-peptide (Class 1 or 2) and the C-terminal Extension peptide (E-peptide Ea or Eb) [3]. Given the conflicting and still unclear data on effects of different IGF-1 isoforms, a recent study investigated whether the muscle overexpression of either propeptides IGF-1Ea or IGF-1Eb isoform impacts sarcopenia and through which mechanisms each isoform acts [5]. Muscle restricted over-expression of both IGF-1Ea and IGF-1Eb isoforms did not induce any significant change in the circulating IGF-1 levels in young mice compared to age-matched wild type animals. Interestingly, consistent with the physiological decline of IGF-1 plasma levels during aging, a strong reduction of IGF-1 levels was observed in old wild type mice [5]. On the contrary, aged transgenic animals showed unchanged levels of circulating IGF-1 compared to young counterparts, thus resulting higher compared to old wild type mice. It is possible to speculate that IGF-1 isoforms, locally expressed, exert an indirect systemic effect, contributing to the maintenance of circulating IGF-1 levels during postnatal life. Indeed, skeletal muscle has recently been identified as an endocrine organ, able to produce and release cytokines and other peptides, such as the myokines, that act in paracrine, autocrine, or endocrine manner [6]. In this context, muscle can be also a source of circulating IGF-1, based on the evidences that IGF-1 is released from exercising muscle into the blood stream [6]. Thus, we can speculate that the reduction of circulating IGF-1 levels in aged wild type mice could be the result of the morpho-functional alterations occurred in muscle. Conversely, transgenic mice, guaranteeing the muscle expression levels of IGF-1 isoforms even at late post-natal life, preserve the capability of muscle to function as endocrine organ, thus contributing to maintain unaltered the circulating IGF-1 levels.
Of note, IGF-1Ea but not IGF-1Eb was able to promote a pronounced muscle hypertrophy and strength in both young and aged mice [5]. Nevertheless, beside the promotion of muscle growth, both IGF-1Ea and IGF-1Eb were able to counteract sarcopenia, negatively modulating the inflame-aging process and activating relevant pathways considered part of a molecular antiaging system, such as autophagy and PGC-1-mediated signaling, which alteration induces neuromuscular junction degeneration and precocious aging [5,7]. Of interest, and in some way paradoxically, the increased levels of IGF-1Ea, but not IGF-1Eb, was correlated with high ROS production [5]. This data suggests that ROS production is part of the promotion and maintenance of a functional hypertrophic phenotype, induced by IGF-1Ea, and supports the evidence that reactive oxygen species are not merely damaging agent but useful signaling molecules to regulate growth, proliferation, differentiation, and adaptation, at least within physiological concentration. Of note, the IGF-1Ea mice were able to minimize oxidative damage in senescent muscle up-regulating, through PGC1-α activation, NRF-2 protein, the master regulator of antioxidant defense [8] and Sirt-1, a factor involved in growth regulation, stress response, endocrine signaling, and extended lifespan.
Moreover, the maintenance of hypertrophic phenotype by IGF-1Ea promoted the activation of additional pathways, such as AMPK, a factor involved in the maintenance of whole-body energy balance and an energy sensor controlling glucose and lipid metabolism. These data are consistent with a model (Figure 1) in which muscle expression of either IGF-1Ea or IGF-1Eb, activating a series of anabolic and compensatory pathways, are able to counteract sarcopenia, preventing muscle loss, strength, and alteration in muscle-nerve interaction. It is also plausible that muscle expression of IGF-1 isoforms, preserving skeletal muscle, might maintain the youth not only of muscle tissue but also of the entire organism, by promoting a local effort activity for a global impact benefit
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
Taurine attenuates catabolic processes related to the onset of sarcopenia
Full text linkSarcopenia that occurs with advancing age is characterized by a gradual loss of muscle protein component due to the activation of catabolic pathways, increased level of inflammation, and mitochondrial dysfunction. Experimental evidence demonstrates that several physio-pathological processes involved in the onset of sarcopenia may be counteracted by the intake of specific amino acids or antioxidant molecules, suggesting that diet may represent an effective strategy for improving the anabolic response of muscle during aging. The non-essential amino acid taurine is highly expressed in several mammalian tissues, including skeletal muscle where it is involved in the ion channel regulation, in the modulation of intracellular calcium concentration, and where it plays an important role as an antioxidant and anti-inflammatory factor. Here, with the purpose to reproduce the chronic low-grade inflammation characteristics of senescent muscle in an in vitro system, we exploited the role of Tumor Necrosis Factor α (TNF) and we analyzed the effect of taurine in the modulation of different signaling pathways known to be dysregulated in sarcopenia. We demonstrated that the administration of high levels of taurine in myogenic L6 cells stimulates the differentiation process by downregulating the expression of molecules involved in inflammatory pathways and modulating processes such as autophagy and apoptosis. Although further studies are currently ongoing in our laboratory to better elucidate the molecular mechanisms responsible for the positive effect of taurine on myogenic differentiation, this study suggests that taurine supplementation may represent a strategy to delay the loss of mass and functionality characteristic of senescent muscles
Inhibition of phosphoinositide 3-kinase/protein kinase B signaling hampers the vasopressin-dependent stimulation of myogenic differentiation
Full text linkArginine-vasopressin (AVP) promotes muscle differentiation, hypertrophy, and regeneration through the combined activation of the calcineurin and Calcium/Calmodulin-dependent Protein Kinase (CaMK) pathways. The AVP system is impaired in several neuromuscular diseases, suggesting that AVP may act as a physiological factor in skeletal muscle. Since the Phosphoinositide 3-kinases/Protein Kinase B/mammalian Target Of Rapamycin (PI3K/Akt/mTOR) signaling plays a significant role in regulating muscle mass, we evaluated its role in the AVP myogenic effect. In L6 cells AKT1 expression was knocked down, and the AVP-dependent expression of mTOR and Forkhead box O3 (FoxO) was analyzed by Western blotting. The effect of the PI3K inhibitor LY294002 was evaluated by cellular and molecular techniques. Akt knockdown hampered the AVP-dependent mTOR expression while increased the levels of FoxO transcription factor. LY294002 treatment inhibited the AVP-dependent expression of Myocyte Enhancer Factor-2 (MEF2) and myogenin and prevented the nuclear translocation of MEF2. LY294002 also repressed the AVP-dependent nuclear export of histone deacetylase 4 (HDAC4) interfering with the formation of multifactorial complexes on the myogenin promoter. We demonstrate that the PI3K/Akt pathway is essential for the full myogenic effect of AVP and that, by targeting this pathway, one may highlight novel strategies to counteract muscle wasting in aging or neuromuscular disorders
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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