1,721,022 research outputs found
Enzymology of extracellular NAD metabolism
Extracellular NAD represents a key signaling molecule in different physiological and pathological conditions. It exerts such function both directly, through the activation of specific purinergic receptors, or indirectly, serving as substrate of ectoenzymes, such as CD73, nucleotide pyrophosphatase/phosphodiesterase 1, CD38 and its paralog CD157, and ecto ADP ribosyltransferases. By hydrolyzing NAD, these enzymes dictate extracellular NAD availability, thus regulating its direct signaling role. In addition, they can generate from NAD smaller signaling molecules, like the immunomodulator adenosine, or they can use NAD to ADP-ribosylate various extracellular proteins and membrane receptors, with significant impact on the control of immunity, inflammatory response, tumorigenesis, and other diseases. Besides, they release from NAD several pyridine metabolites that can be taken up by the cell for the intracellular regeneration of NAD itself. The extracellular environment also hosts nicotinamide phosphoribosyltransferase and nicotinic acid phosphoribosyltransferase, which inside the cell catalyze key reactions in NAD salvaging pathways. The extracellular forms of these enzymes behave as cytokines, with pro-inflammatory functions. This review summarizes the current knowledge on the extracellular NAD metabolome and describes the major biochemical properties of the enzymes involved in extracellular NAD metabolism, focusing on the contribution of their catalytic activities to the biological function. By uncovering the controversies and gaps in their characterization, further research directions are suggested, also to better exploit the great potential of these enzymes as therapeutic targets in various human diseases
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
The crystal structure of human alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase in complex with 1,3-dihydroxyacetonephosphate suggests a regulatory link between NAD synthesis and glycolysis
[Metabolism of NAD+ in the nuclei of human placenta]
It has long been known that the major function of NAD+ is as an electron carrier in various biological oxidation-reduction systems. From many papers it is evident that NAD+ is involved as substrate in ADP-ribosylation reactions. We have focused our attention on two chromatin enzymes: NMN-adenylyltransferase that catalyzes reversible synthesis of NAD+ utilizing ATP and NMN, and poly(ADP-ribose)polymerase that covalently modifies nucleosomal proteins through poly ADP-ribosylation reactions. Here we provided evidence of these activities in a system of isolated nuclei from human placenta. The data presented in this report show that purified nuclei might be useful to study the nuclear location of these enzymes and their reciprocal interaction
Glioma cells induce g-glutamyl-transpeptidase activity in cultured blood but not lymphatic endothelial cells
Glial cells have been shown to induce enzyme activities, which are characteristically high in brain capillaries, in cerebral and non cerebral endothelial cells in culture. We evaluated the activity of g -glutamyl transpeptidase (gGT) in freshly isolated (ex vivo) bovine blood (BEC) and lymphatic (LEC) endothelial cells. We also tested the effect of C6 glioma cell conditioned medium (GCM) on gGT activity of BEC and LEC in primary culture. Ex vivo BEC had a high g GT activity, only 9% of which was retained in culture. After exposure to GCM, however, g GT activity of cultured BEC was twofold higher than with
control medium. By contrast g GT activity was extremely low in ex vivo LEC and did not significantly increase in cultured LEC exposed to GCM. These data show that the basal levels of g GT are markedly different in BEC and LEC and also that, unlike BEC, LEC are not capable of producing more g GT in response to glial stimulation
Nitriding and post-oxidation treatments on 17-4PH stainless steel: optimization of the process to preserve high corrosion resistance
The structure of superficial lymphatics in the human thigh: precollectors
BACKGROUND:
Little is known about the morphology of precollectors, the lymphatic vessels connecting the absorbing and the collecting vessels, which are regarded as the initial drainage routes of lymph. The aim of this study was to describe the structural features of human precollectors.
METHODS:
Samples of fat from around the saphenous veins were obtained from patients undergoing varicotomy, and serial sections were observed under light and transmission electron microscopy. Tridimensional reconstructions were also obtained by computer analysis.
RESULTS:
Precollectors were characterized by an irregular and discontinuous arrangement of smooth muscle cells in their wall. This arrangement was unrelated to the site of valves. When present, muscular elements were arranged helicoidally, as shown in tridimensional reconstructions. Under transmission electron microscopy, the endothelium of precollectors was similar to that of absorbing lymphatic vessels, irrespective of the presence of smooth muscle cells, and was thin, rich in pinocytotic vesicles, supported by a discontinous basal lamina, and connected by anchoring filaments to the surrounding connective tissue. Myoendothelial contacts were frequent. Valves were similar to those of collecting vessels, except for the presence of numerous zonulae adherentes connecting the characteristic "tip cells" of the free edge.
CONCLUSIONS:
Human thigh precollectors are characterized by the alternation of portions with a well-developed muscular coat and portions with an absorbing structure. These morphological features suggest that the precollectors contribute to fluid absorption and lymph propulsion. The frequent myoendothelial contacts suggest that smooth muscle contraction is regulated locally
Variations on the Author
“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
We 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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