1,720,990 research outputs found
Human sirtuins: an overview of an emerging drug target in age-related diseases and cancer.
No full textSir2-like proteins (Sirtuins) are a class of enzymes conserved throughout the kingdoms of life. In fact, from Archaea to Mammals, these (class III) NAD+-dependent deacetylases catalyse the removal of the acetyl moiety from a substrate protein. Sirtuins show a conserved central catalytic domain with two more variable amino- and carboxy-terminal flanking regions. Amino acid comparison of these central conserved catalytic core sequences allows us to divide Sirtuins into five different classes (I, II, III, IV and U). These proteins differ in their subcellular localization (i.e. in Eukaryotes they can be found in the nucleus, cytoplasm or mitochondria). In humans there are seven Sirtuins (SIRT1-7) that are implicated in various physiological processes including aging and age-related disorders such as neoplasms, cardiovascular, metabolic and neurodegenerative diseases, and inflammation. Nowadays, the estimated life expectancy is definitely longer than in the past thus, we may consider all aging-related problems as having a strong social impact. Consequently, Sirtuins are emerging, particularly from a pharmacological point of view, as new and valuable drug targets
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
Crystals of the hydrogenase maturation factor HypF N-terminal domain grown in microgravity, display improved internal order
No full textSynthesis of the active [Ni–Fe]-hydrogenase in prokaryotes requires a series of ancillary maturation factors. Among them, the HypF maturation factor is a multidomain 82 kDa protein, whose N-terminal domain displays sequence and structural similarities to acylphosphatases. Acylphosphatases are small enzymes that are able to catalyze carboxyl-phosphate bond hydrolysis in acylphosphates, as well as in nucleoside di- and tri-phosphates and in arylphosphates. Here, we present a crystallographic comparison between microgravity and earth-grown crystals of the HypF N-terminal domain. Both crystals were of excellent quality, thereby allowing us to collect very high resolution datasets. A detailed analysis of data collection and refinement statistics, together with an analysis of the diffraction pattern showed that microgravity would appear to further improve the internal order of crystals
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
One-Pot Synthesis and Antiproliferative Activity of Highly Functionalized Pyrazole Derivatives
No full textA series of highly functionalized pyrazole derivatives has been prepared by a one-pot, versatile and regioselective procedure. Pyrazoles 1–29 were tested in cell-based assay to assess their antiproliferative activity against a panel of tumour cells. Additionally, the cytotoxicity of prepared compounds was evaluated against normal human fibroblasts. The antiproliferative activity of the synthesized molecules emerged to be affected by the nature of the substituents of the pyrazole scaffold and derivatives 21–23 proved to inhibit the growth of melanoma and cervical cancer cells. Compound 23 was identified as the most active derivative and docking simulations predicted its ability to interact with estrogen receptors
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
Diversity-oriented synthesis of novel heterocyclic compounds and their preliminary evaluation as antimalarial agents
No full textPush-pull alkenes refer to substituted alkenes bearing one or two electron-donating groups at one end of the double bond and one or two electron-accepting groups at the other end. These chemical properties make push-pull alkenes particularly reactive with electrophilic and nucleophilic species and therefore they have been widely used as building blocks in organic synthesis, especially for the preparation of heterocycle derivatives. In particular, ketene N,S- and S,S-acetals are the most representative class of push-pull alkenes used in organic synthesis. Recently, we reported a stepwise synthetic procedure through ketene N,S-acetal intermediates for the preparation of novel 5-anilinopyrazoles 1 endowed with antimalarial activities. To further extend the SARs of this class of compounds, we designed and synthesized a new series of 5-aminopyrazoles and 4-aminopyrimidines (derivatives 2 and 3) bearing all the structural determinants for the antimalarial activity. The unreported molecules were synthesized trough a versatile synthetic procedure which involved subsequent isolation of ketene S,S-acetals A and N,S-acetals B that were then cyclized with hydrazine or guanidine to afford the desired compounds. All the new isolated derivatives were screened against D10 and W2 Plasmodium strains and their cytotoxicity was evaluated on normal fibroblast cells by MTT assay
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