1,720,967 research outputs found
Extracellular calcium and cAMP: second messengers as "third messengers"?
No full textCalcium and cyclic AMP are familiar second messengers that typically become elevated inside cells on activation of cell surface receptors. This article will explore emerging evidence that transport of these signaling molecules across the plasma membrane allows them to be recycled as "third messengers," extending their ability to convey information in a domain outside the cell
The role of Store-Operated Cyclic AMP Signalling (SOcAMPS) in cardiac physiology and pathology: an in vitro study on neonatal rat cardiomyocytes.
No full textBackground and Aims: Store-Operated Cyclic AMP Signaling (SOcAMPS) represents a recently
identified mechanism of cross-talk between Ca2+ and cAMP signals. In this process, depletion of
Ca2+ in the endoplasmic reticulum (ER) leads to increases in cAMP levels, independently of
cytosolic Ca2+ changes. Expression and functionality of STIM1 (Stromal Interaction Molecule 1), a
transmembrane ER Ca2+ sensor protein, is necessary for SOcAMPS to occur. Interestingly, recent
reports have demonstrated a critical role for STIM1 in the development of cardiac hypertrophy, a
process notoriously controlled both by Ca2+ and cAMP signaling. Here we aimed to evaluate
whether SOcAMPS was manifest in neonatal rat cardiomyocytes and its potential role in cardiac
cell hypertrophy.
Methods: To monitor changes in cAMP levels, real time imaging experiments were performed on
neonatal rat cardiomyocytes transiently transfected with an EPAC-based fluorescent probe for
[cAMP], EPAC H30. Fura-2 and Fluo-4 were used to monitor cytosolic Ca2+ levels and an ER/SR
targeted probe, D1ERcameleon, was used to measure ER [Ca2+]. Long term incubation (48h) of
cardiomyocytes with angiotensin II (1 μM) and aldosterone (1 μM) was used to induce "in vitro"
cell hypertrophy. Increases in cell size and/or sarcomere alignment were monitored microscopically
after labeling with phalloidin-TRITC.
Results: To verify the existence of SOcAMPS in neonatal rat cardiomyocytes, cells were stimulated
in Ca2+-free Ringer's solutions with the low affinity membrane permeant Ca2+ chelator TPEN
(1mM), able to induce a reduction of SR Ca2+ levels ([Ca2+]SR) without affecting cytosolic
[Ca2+]. SR Ca2+ measurements demonstrated that under these experimental conditions, 1 mM
TPEN led to a reduction in intraluminal [Ca2+] that was 50,5±2,4% (8 exp, 11 cells, p<0.001) of
the maximal store depletion. Parallel experiments performed with the EPAC H30 cAMP sensor
showed increases in [cAMP] that were 26,5±3% (13 exp, 13 cells, p<0.001) of the maximum delta
ratio. In the presence of 5 μM Forskolin (FRSK) the TPEN-induced cAMP augmentation resulted
63,7±3,9% of the maximal response (16 exp, 19 cells, p<0.001). Also depletion of SR by the Ca2+
ionophore ionomycin (10 μM) was found to induce significant cAMP increases both in the absence
and presence of FRSK. The participation of STIM1 in the observed phenomenon was proven by the
47 % reduction of the TPEN+FRSK induced [cAMP] signal after transfection of cells with a
shRNA against STIM1 (6 exp, p<0,01). To evaluate the putative role of SOcAMPS in cardiac
hypertrophy, cAMP measurements were performed on angio+aldo treated cells and compared to
control cardiomyocytes. Under these experimental conditions a 20% increase of the TPEN+FRSK
induced response was observed in hypertrophic myocytes (16 exp, p<0,01).
Conclusions: These data straightforwardly establish, for the first time, the existence of SOcAMPS
in the neonatal cardiomyocyte cell model. Also, a significantly increased SOcAMP signalling was
shown to exist in hypertrophic cardiomyocytes. Further experiments to ascertain whether a causeand-
effect relationship exists between SOcAMPS and cardiac cell hypertrophy are in progress
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
Dispelling 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
The inner and outer compartments of mitochondria are sites of distinct cAMP/PKA signaling dynamics
Full text linkCyclic AMP (cAMP)-dependent phosphorylation has been reported to exert biological effects in both the mitochondrial matrix and outer mitochondrial membrane (OMM). However, the kinetics, targets, and effectors of the cAMP cascade in these organellar domains remain largely undefined. Here we used sensitive FRET-based sensors to monitor cAMP and protein kinase A (PKA) activity in different mitochondrial compartments in real time. We found that cytosolic cAMP did not enter the matrix, except during mitochondrial permeability transition. Bicarbonate treatment (expected to activate matrix-bound soluble adenylyl cyclase) increased intramitochondrial cAMP, but along with membrane-permeant cAMP analogues, failed to induce measureable matrix PKA activity. In contrast, the OMM proved to be a domain of exceptionally persistent cAMP-dependent PKA activity. Although cAMP signaling events measured on the OMM mirrored those of the cytosol, PKA phosphorylation at the OMM endured longer as a consequence of diminished control by local phosphatases. Our findings demonstrate that mitochondria host segregated cAMP cascades with distinct functional and kinetic signatures.Version of Recor
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
- …
