1,721,018 research outputs found
Regularizing the regular: The phenomenon of overregularization in Esperanto-speaking children
No full textThis article deals with the phenomenon of overregularization in a language itself regular, such as Esperanto, in children who acquire it as a mother tongue together with one or two national languages. The study is based on diaries kept by Esperanto-speaking parents and analyzes overregularization on the basis of both morpho-syntactic complexity and semantic elaboratedness. Results show an increase of these measures with age
Alteration of flavin homeostasis in neuromuscular disorders and cancer
No full textRiboflavin, otherwise known as vitamin B2, is an essential dietary component and represents the precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), the redox enzymatic cofactors required for mitochondrial terminal metabolism and for the functionality of mitochondrial respiratory chain. Protein folding, ROS production and defense, as well as redox epigenetics also depend on cellular supply of FAD.
FAD formation in different cells starts from riboflavin uptake, which occurs via specialized carrier-mediated processes which are supported by three specific members of the solute carrier family 52 (SLC52A), identified and named respectively RFVT1, RFVT2 and RFVT3. Once in the cell, riboflavin is converted to FMN by riboflavin kinase (RFK, EC2.7.1.26) and FMN is converted, in turn, to FAD by FAD synthase (FADS, EC 2.7.7.2), coded by human FLAD1 gene. Alternative splicing of the FLAD1 gene generates different hFADS isoforms, with different sub-cellular localization, most of them containing and a C-terminal 3-phosphoadenosine 5-phosphosulfate (PAPS) reductase domain, which per se performs the FAD synthase activity and a N-terminal molybdopterin binding (MPTb) domain, which could perform a FAD hydrolase activity.
Alterations of FAD synthesis and RFVT1 impairment have been correlated with a rare inherited neuro-muscular disorders, in some cases treatable with high doses of Riboflavin, named Multiple Acyl-CoA Dehydrogenase Deficiency (MADD, MIM: 231680). Here we describe a novel case of MADD caused by a truncating variant in FLAD1 resulting in a premature STOP codon in exon 2. Studies, carried out on patient fibroblasts, revealed a dramatic reduction in FADS protein level with corresponding reduction in FAD synthesis rate and in mitochondrial flavoenzyme amounts. The residual FAD activity measured could result from the expression of a novel isoform named 6, lacking MPTb domain, relevant for patient survival [1]. Immunoblotting analysis of RFVTs revealed a reduction in RFTV2 protein amount in fibroblasts of this patient, which is in line with the reduction of the total flavin cellular content observed by HPLC. The secondary defect of riboflavin transport rate in MADD patient, laying the foundations for explaining riboflavin therapy, links MADD to Brown-Vialetto-Van-Laere Syndrome (BVVLS, MIM: 21153; 614707) [2]. It is a neurological disorder characterized by bilateral sensoneural deafness, respiratory insufficiencies and progressive ponto-bulbar palsy, linked to mutations in RFVT2 and RFVT3 genes. A significant reduction in the intracellular levels of FMN and FAD was found in BVVLS patient fibroblasts grown in low extracellular riboflavin conditions [2].
We also pointed our attention on dysregulation of RFVTs expression linked to human colorectal [3] and some other types of cancer, generating a profound alteration of flavin cofactor homeostasis. Changing the level of RFVTs expression as a possible mean to reprogram cellular flavoproteome will be discussed
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
MODULATING CELLULAR FLAVIN COFACTOR LEVELS IN HUMANS VIA THE BI-FUNCTIONAL AND MONOFUNCTIONAL FLAD1 GENE PRODUCTS
No full textDispelling 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
Continuous and Discontinuous Approaches to Study FAD Synthesis and Degradation Catalyzed by Purified Recombinant FAD Synthase or Cellular Fractions
No full textRiboflavin, or vitamin B2, is the precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), essential redox (and sometimes non-redox) cofactors of a large number of flavoenzymes involved in energetic metabolism, protein folding, apoptosis, chromatin remodeling, and a number of other cell regulatory processes.The cellular and subcellular steady-state concentrations of flavin cofactors, which are available for flavoprotein biogenesis and assembly, depend on carrier-mediated transport processes and on coordinated synthesizing/destroying enzymatic activities, catalyzed by enzymes whose catalytic and structural properties are still matter of investigation.Alteration of flavin homeostasis has been recently correlated to human pathological conditions, such as neuromuscular disorders and cancer, and therefore we propose here protocols useful to detect metabolic processes involved in FAD forming and destroying.Our protocols exploit the chemical-structural differences between riboflavin, FMN , and FAD , which are responsible for differences in the spectroscopic properties (mainly fluorescence) of the two cofactors (FMN and FAD); therefore, in our opinion, when applicable measurements of fluorescence changes in continuo represent the elective techniques to follow FAD synthesis and degradation. Thus, after procedures able to calibrate flavin concentrations (Subheading 3.1), we describe simple continuous and rapid procedures, based on the peculiar optical properties of free flavins, useful to determine the rate of cofactor metabolism catalyzed by either recombinant enzymes or natural enzymes present in cellular lysates/subfractions (Subheading 3.2).Fluorescence properties of free flavins can also be useful in analytical determinations of the three molecular flavin forms, based on HPLC separation, with a quite high sensitivity. Assaying at different incubation times the molecular composition of the reaction mixture is a discontinuous experimental approach to measure the rate of FAD synthesis/degradation catalyzed by cell lysates or recombinant FAD synthase (Subheading 3.3). Continuous and discontinuous approaches can, when necessary, be performed in parallel
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