1,720,960 research outputs found
Is mammalian Apg/Aut homologues espresssion involved in induction and modulation in autophagy in rat hepatocytes?
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Calpain and mitochondrial dysfunction in Ca2+ overloaded cardiomyocytes
No full textIntracellular Ca2+ overload and mitochondrial dysfunction are considered major causes of ischemia-induced cell death. An increase in intracellular Ca2+ ([Ca2+]i) can also cause the activation of calpains. Although the increased activity of these proteinases is suggested to play a relevant role in different forms of cell death, the relationship between calpain activation and mitochondrial dysfunction is not elucidated yet. To this aim the fluorescent potentiometric probe JC-1 was used to assess mitochondrial membrane potential (MMP) in HL-1 cardiomyocytes. A persistent elevation in [Ca2+]i as detected by Fluo-4 FF fluorescence was obtained by adding HL-1 cells with the calcium ionophore A23187 (1 uM) in the presence of 1 mM vanadate to inhibit P-type ATPases and replacing NaCl with KCl in the incubation buffer. The rise in [Ca2+]i was followed by MMP fall which occurred in 50% of the cells 30 min after A23187 addition. Mitochondrial deenergization was concomitant with calpain activation as detected by the proteolysis of a synthetic peptide (Suc-LLVY-AMC) and the occurrence of cell necrosis as detected by LDH release. Interestingly the extent of enzyme release correlated with the number of cells displaying MMP fall. Cell death was likely due only to necrosis since cleavage of PARP-1 and caspase-3 was not detected. Calpains inhibitors, like PD150606 (30 uM) and calpeptin (100 uM), reduced by 60% both LDH release and mitochondrial deenergization. Therefore the increase in [Ca2+]i does not appear to cause mitochondrial deenergization per se. Interestingly, HL-1 staining with anti calpain antibodies demonstrated that calpains colocalize with mitochondria. In conclusion, the present data suggest that calpain activation is a causative factor of mitochondrial dysfunction under conditions of intracellular Ca2+ overload
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
DPP4 inhibitor and pharmaceutical application thereof
No full textThe present invention provides a Dpp4 inhibitor which comprises a leucine derivative of the following formula (1) or a methionine derivative of the following formula (2): wherein each R1 and R3 represents a hydrogen atom (H) and an L-amino acid residue; R2 represents a hydroxyl group (OH), alkoxy group having 1 to 6 carbon atoms, amino group (NH2), alkylamino group having 1 to 6 carbon atoms, glycine residue, -alanine residue, L-amino acid (except for proline, alanine and phenylalanine) residue or L-amino-acid amide (except for proline amide, alanine amide and phenylalanine amide) residue; and R4 represents a hydroxyl group (OH), alkoxy group having 1 to 6 carbon atoms, amino group (NH2), alkylamino group having 1 to 6 carbon atoms, glycine residue, -alanine residue, L-amino acid (except for proline and alanine) residue or L-amino-acid amide (except for proline amide and alanine amide) residue. These derivatives also act as autophagy regulators
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
Activation of PPARalpha is followed by its down regulation in murine atrial cell line HL-5
No full textBesides the established role of PPARalpha in modulating lipid metabolism, a growing body of evidence suggests the involvement of this receptor in a wide variety of pathological processes including the failure of contraction resulting from myocardial hypertrophy or ischemia. The present study was aimed at characterizing the pattern of response to PPARalpha stimulation in an experimental model suitable for both genetic manipulation and pharmacological screening. To this aim, we utilized HLS a sub clone originated from HLl, a murine atrial cell line. These cardiomyocytes display spontaneous contraction along with several phenotypic characteristics of adult cardiomyocytes. Transcript characterization by RT-PCR in the HLS subclone showed high levels of mRNA for sarcomeric proteins, such as alpha cardiac actin, TnC, Tnl, TnT and adult isoform of myosin heavy chain (MHCalpha), while the embryonic isoform (MHCbeta) was practically undetectable. Together with metabolic effectors like muscle CPT1, CPT2, GLUT4, UCP2, UCP3 and adaptive factors (ANF, TNFAlpha, HlF alpha and beta), the HLS cell line constitutively expresses to various extents mRNA coding for PPARs (alpha, beta and gamma) and for the obligatory heterodimers RXRs. Biochemical analysis confirmed the translation of the messenger coding for the nuclear receptors (isoforms alpha and gamma). Treating HLS cells with PPARalpha agonists, such as oleate or WYI4643, induced a significant increase in long-chain acyl-CoA dehydrogenase and UCP2 mRNA levels. Similar results have been recently reported for neonatal cardiomyocytes. Interestingly, the incubation of HLS with oleate resulted in a gradual decrease of PPARalpha messenger which was reduced to 25% of untreated cells after 48 hours. In conclusion, the present results suggest the occurrence of a feed-back control capable of down-regulating the receptor following its activation. Finally, HL-S cardiomyocytes appear a suitable model to elucidate the role of PPARalpha in pathophysiological conditions and characterize its pharmacological modulation
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