1,721,772 research outputs found
Hydrogen sulfide metabolism in cancer and homocystinuria: towards the development of new pharmacological strategies
Get PDFHydrogen sulfide (H2S), along with nitric oxide (NO) and carbon monoxide (CO), belongs to a small group of gaseous signalling molecules termed ‘gasotransmitters’. H2S is involved in important physiological and pathological processes and exerts a dose-dependent effect on cellular bioenergetics, acting at higher levels as an inhibitor of mitochondrial cytochrome c oxidase or stimulating ATP synthesis at lower concentrations. A growing number of pathologies are reportedly associated with alterations of H2S metabolism. Here, the human H2S metabolism was investigated in classical homocystinuria and in cancer; furthermore, it was explored a new pharmacological strategy against cancer based on human ferritin (Hft) as a drug delivery system. Classical homocystinuria is a rare genetic disease, associated with mutations in the gene encoding the heme-containing enzyme cystathionine β-synthase (CBS), a major source of H2S in humans. CBS is allosterically activated by S-adenosyl-L-methionine, but inhibited by CO or NO. Here, it was found that the pathogenic p.P49L variant of human CBS, as produced in E. coli and purified, displays reduced affinity for the PLP (pyridoxal 5’-phosphate) cofactor and increased affinity of the ferrous heme for CO. This could lead to enzyme inhibition at physiological CO concentrations, thereof representing a pathogenic mechanism in classical homocystinuria. Hydrogen sulfide plays an important role also in colon cancer where it promotes angiogenesis and, interestingly, energy metabolism. Here, the H2S catabolism was explored in colon cancer model cells (SW480) exposed to hypoxia, a common factor of tumoral microenvironment that promotes tumor cell survival and propagation. Cells were grown under either normoxic (20% O2) or hypoxic (1% O2) conditions and their ability to metabolize H2S at the mitochondrial level was assayed by high resolution respirometry. Intriguingly, exposure to hypoxic conditions for 24 hours, while reducing the mitochondrial mass and the maximal efficacy to metabolize sulfide, was found to increase the expression of the H2S-metabolizing mitochondrial enzyme sulfide:quinone oxidoreductase. These effects induced by hypoxia may affect the H2S levels in SW480 cells, pointing to H2S catabolism as a potential drug target in colon cancer. Finally, in order to design new therapeutic strategies against cancer, it was obtained an engineered human ferritin-based nanocarrier (HFt-MP-PASE), able to effectively incorporate and deliver the chemotherapeutic drug mitoxantrone with high killing efficacy against model cells of colon cancer progression (SW480 and SW620)
Geradenkongruenzen im dreidimensionalen Raum, dessen absolutes Gebilde aus zwei reellen Ebenen und zwei reellen Punkten auf deren Schnittlinie besteht
No full text[Borisov Adrian V.; Borisov A.; Borisov Adrijan V.; Borisov Adriyan V.; Borisov Andriyan; Борисов Адриян В.]Bulgarian. Russian, German summar
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
Kanonisches Repere der Geradenkomplexe im dreidimensionalen Raum, dessen absolutes Gebilde aus zwei reellen Ebenen und zwei reellen Punkten auf deren Schnittlinie besteht
No full text[Borissow Adrian; Borisov A.; Borisov Adrian; Borisov Adrijan V.; Borisov Adriyan V.; Borisov Andriyan; Борисов Адриян]Bulgarian. Russian, German summar
Kurven und Flächen im dreidimensionalen Raum mit Absolutem, das aus zwei reellen Ebenen und zwei reellen Punkten ihrer gemeinsamen Geraden besteht
No full text[Borisov Adrian; Borisov A.; Borisov Adrijan V.; Borisov Adriyan V.; Borisov Andriyan; Борисов Адриян]Bulgarian. Russian, German summar
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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