1,721,057 research outputs found
Multitasking Roles of the Mammalian Deacetylase SIRT6
No full textSirtuins (SIRT) are highly conserved proteins first described as nicotinamide adenine dinucleotide (NAD+)-dependent type III histone deacetylases. They are the mammalian homologs of the SIR2 gene found in yeast. Seven homologs (SIRT1–7) have been described, all sharing an NAD+ binding catalytic domain comprising 275 amino acids and variable N and C termini. This difference in their terminal domains dictates distant roles and cellular localization of the members of the sirtuin family. In this review, we will focus on the chromatin deacetylase SIRT6, a multitasking protein with various roles in metabolism, development, DNA repair, and cancer. We will provide current knowledge in the context of its structure, enzymatic activity, and regulation. We will discuss its role in genomic stability and DNA repair, metabolism, and development. Finally, we will review SIRT6’s involvement in several diseases
SIRT3 deacetylase: the Jekyll and Hyde sirtuin
Get PDFPost‐translational modifications have crucial roles in regulating the functions of many eukaryotic proteins. Among them, lysine acetylation has been traditionally studied in the context of nuclear histone modifications, and was one of the first to be described as part of the ‘histone code’ hypothesis (Kim et al, 2006). More recently, work from several groups has demonstrated that lysine acetylation also modulates the activity of several non‐histone proteins. In this context, this modification seems particularly abundant on mitochondrial proteins (Schwer et al, 2009). However, the way in which acetylation influences enzyme function and metabolic reprogramming in pathological states remains unknown. In an article published online this month in EMBO reports, Sack and colleagues shed new light on the role of mitochondrial SIRT3 deacetylase during paracetamol‐induced toxicity, describing the mitochondrial protein aldehyde dehydrogenase 2 (ALDH2) as a new target of SIRT3, and a protective role for protein acetylation in this context.Fil: Silberman, Dafne Magali. Harvard Medical School; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Mostoslavsky, Raul. Harvard Medical School; Estados Unido
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
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Genetic Determinants and Epigenetic Effects of Pioneer Factor Occupancy
No full textTranscription factors (TFs) are the core drivers of gene regulatory networks that control developmental transitions and a complete understanding of how they access, alter and maintain specific gene expression patterns remains an important goal. To begin a systematic dissection of the molecular components that either enable or constrain TF activity, we investigated the genomic occupancy of a set of previously defined pioneer factors, FOXA2, GATA4 and OCT4 in both endogenous and ectopic settings. We find that all three factors display cell type specific occupancy even with super-physiological expression conditions, but only FOXA2 and GATA4 display, in both endogenous and ectopic conditions, low enrichment sampling of additional loci that are occupied in alternative lineages. Ectopic co-expression of FOXA2 and GATA4 can stabilize sites that were previously only sampled. In general, we observe little influence of the chromatin state on FOXA2 or GATA4 enrichment, but a bias towards open chromatin for ectopic OCT4 targets. Finally, we demonstrate that FOXA2 occupancy and changes to DNA accessibility at silent cis-regulatory elements can occur when the cell cycle is halted in G1, but surprisingly, subsequent changes in DNA methylation require DNA replication. Taken together, our results provide several new molecular insights that contribute to our basic understanding of gene regulation and pave the way for a more rational use of ectopic TFs for cellular reprogramming.Medical SciencesMedical Science
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe 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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Investigating molecular and regulatory boundaries of the pluripotent state
No full textAlthough progressively restricted to specialized functions during ontogeny, differentiated somatic cell nuclei can be experimentally directed to other cell types, including those with complete developmental potential. The technical challenges inherent to initial nuclear reprogramming methods such as somatic cell nuclear transfer and cell fusion pose significant hurdles to precisely dissecting the regulatory programs governing cell identity. The discovery of reprogramming via ectopic delivery of a defined set of transcription factors provided a tractable platform to uncover molecular characteristics of cellular specification and differentiation, cell type stability, and pluripotency. Despite ongoing progress, a detailed molecular understanding of the terminal events that coordinate the reprogramming from somatic to pluripotent cell remains elusive. To better understand how transcription factors mediate such a dramatic change in cell state, we optimized a time course-based model where differentiating cells are systematically challenged to reacquire pluripotency. Using this approach, we identify a transient period of time after pluripotency exit where cells are developmentally determined, yet respond to induction of exogenous reprogramming factors by reverting to the pluripotent state in a near-deterministic fashion. This brief period is followed by a rapid decline into somatic-like reprogramming kinetics and efficiency. By investigating transcriptional, epigenetic, and transcription factor dynamics on either side of this window, we find several key molecular parameters that prescribe the regulatory boundary between non-pluripotent and pluripotent identities. We show that the route to pluripotency is directed through OCT4 engagement at a distinguishable subset of pluripotent-state enhancers that are uniquely regulated during differentiation in vitro and in vivo and encode a distinctive combination of cis-regulatory sequences. From these data, we present a model where delayed silencing of these enhancers predisposes them to function as primary genetic targets for the final, deterministic transition into molecular pluripotency.Medical SciencesMedical Sciencespluripotency; reprogramming; iPSC; epigenetic
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