1,720,968 research outputs found
Obesity: adipogenesis and insulin resistance
No full textThis meeting focused on the recent developments in the fields of adipogensis and insulin resistance. In particular, the molecular mechanisms presented were those that are likely to be relevant as drug discovery targets for the treatment of obesity and diabetes. New compounds included the LIFR antagonist, hLIF05, and LG- 100641, a selective antagonist of PPARgamma but with insulin sensitizing actions in adipocytes. The small insulin sensitizers discussed were CLX-0901, isolated from plant extracts and currently in phase I clinical trials, TLK-17411, a small synthetic compound and S-15261, which increases insulin sensitivity.</p
Effect of paracetamol on mitochondrial membrane function in rat liver slices
No full textThe effect of paracetamol on mitochondrial function was studied using rat liver slices. Changes in the potential of the mitochondrial and plasma membrane were monitored using [3H]-triphenylmethylphosphonium (TPMP+) and [14C]thiocyanate (SCN-) probes, respectively. Liver slices were exposed to 10 mM paracetamol for various time periods (0-360 min) after loading with TPMP+. The release of TPMP+ which correlates with a decrease in the mitochondrial membrane potential became significant after 30 min incubation with 10 mM paracetamol. The change in the mitochondrial membrane potential was shown to be independent of cytochrome P450 activity. No significant change in plasma membrane potential was observed, until the release of lactate dehydrogenase (LDH) had begun, 4 hr after exposure, reflecting the ultimate stages of cell injury by paracetamol. These results suggest that paracetamol elicits a direct effect on the mitochondrial function before cell injury develops and adds further evidence to the role of mitochondria in paracetamol toxicity.</p
Nicotinamide inhibits cyclic ADP-ribose-mediated calcium signalling in sea urchin eggs
Full text linkCyclic ADP ribose (cADPR) is a potent Ca(2+)-releasing agent, and putative second messenger, the endogenous levels of which are tightly regulated by synthetic (ADP-ribosyl cyclases) and degradative (cADPR hydrolase) enzymes. These enzymes have been characterized in a number of mammalian and invertebrate tissues and their activities are often found on a single polypeptide. beta-NAD+, cGMP and nitric oxide (NO) have been reported to mobilize Ca2+ in the sea urchin egg via the cADPR-mediated pathway. We now report that in sea urchin egg homogenates, nicotinamide inhibits the Ca(2+)-mobilizing action of beta-NAD+, cGMP and NO, but has no effect on cADPR-induced Ca2+ release. Moreover, nicotinamide inhibits cGMP-induced regenerative Ca2+ waves in the intact sea urchin egg. By successfully separating the cADPR-metabolizing machinery from that which releases Ca2+, we have shown that nicotinamide inhibits cADPR-mediated Ca2+ signalling at the level of cADPR generation. Importantly, nicotinamide had no effect upon the hydrolysis of cADPR, and its selective action on cyclase activity was supported by its inhibition of purified Aplysia ADP-ribosyl cyclase, which does not exhibit detectable hydrolytic activity. The action of nicotinamide in blocking Ca2+ release by beta-NAD+, cGMP and NO strongly suggests that these agents act as modulators of cADPR synthesis rather than to sensitize calcium release channels to cADPR.</p
Effect of dietary fat on the in vitro hepatotoxicity of paracetamol
No full textIn the present study, we have examined the effect of dietary fat on paracetamol-induced liver injury in an in vitro rat liver slice model. Rats were fed, for 7-10 days, diets containing either butter or polyunsaturated vegetable margarine, two fat sources commonly consumed in the human diet. Liver slices were then exposed to paracetamol for 2 hr and further incubated for 4 hr without paracetamol. Cell damage in the slices was quantified at 6 hr by measuring leakage of lactate dehydrogenase, increase in water content and potassium loss. Covalent binding of radioactive paracetamol to liver and the membrane fatty acid composition of the liver were also measured. Liver slices from rats fed butter diets were significantly more sensitive to the toxic effects of paracetamol than those from margarine fed rats. The membrane lipid composition of the livers also reflected the differing fatty acid content of the two diets.</p
LEM-PCR: A method for determining relative transcript isoform proportions using real-time PCR without a standard curve
No full textMany genes express multiple transcript isoforms generated by alternative splicing of mRNA. Using real-time PCR, it is straightforward to determine the relative expression level of each isoform independently. However, it is less trivial to determine the relative proportions of different isoforms in a cDNA sample. The relative proportions of different isoforms can be important, as a small change in a highly abundant transcript may be more relevant than a large change in a minimally expressed transcript. Currently, determining the relative proportions of isoforms requires the construction of a standard curve using recombinant plasmid DNA or genomic DNA. As recombinant or genomic DNA standards often amplify with different efficiencies to cDNA samples, they may give under- or overestimations of isoform abundances. The method described in this article uses a titration curve generated from the same cDNA samples measured in the experiment. By using samples with different levels of separate isoforms, it is possible to derive linear equations which, when solved, allow the determination of the proportion of each isoform within the samples under study.</p
Tumour necrosis factor-α inhibits adipogenesis via a β-catenin/TCF4(TCF7L2)-dependent pathway
No full textTumour necrosis factor-α (TNF-α), a proinflammatory cytokine, is a potent negative regulator of adipocyte differentiation. However, the mechanism of TNF-α-mediated antiadipogenesis remains incompletely understood. In this study, we first confirm that TNF-α inhibits adipogenesis of 3T3-L1 preadipocytes by preventing the early induction of the adipogenic transcription factors peroxisome proliferator-activated receptor-γ (PPARγ) and CCAATαenhancer binding protein-α (C/EBPα). This suppression coincides with enhanced expression of several reported mediators of antiadipogenesis that are also targets of the Wnt/ β-catenin/T-cell factor 4 (TCF4) pathway. Indeed, we found that TNF-α enhanced TCF4-dependent transcriptional activity during early antiadipogenesis, and promoted the stabilisation of β-catenin throughout antiadipogenesis. We analysed the effect of TNF-α on adipogenesis in 3T3-L1 cells in which β-catenin/TCF signalling was impaired, either via stable knockdown of β-catenin, or by overexpression of dominant-negative TCF4 (dnTCF4). The knockdown of β-catenin enhanced the adipogenic potential of 3T3-L1 preadipocytes and attenuated TNF-α-induced antiadipogenesis. However, β-catenin knockdown also promoted TNF-α-induced apoptosis in these cells. In contrast, overexpression of dnTCF4 prevented TNF-α-induced antiadipogenesis but showed no apparent effect on cell survival. Finally, we show that TNF-α-induced antiadipogenesis and stabilisation of β-catenin requires a functional death domain of TNF-α receptor 1 (TNFR1). Taken together these data suggest that TNFR1-mediated death domain signals can inhibit adipogenesis via a β-catenin/TCF4-dependent pathway.</p
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
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