1,720,962 research outputs found
Full-length and not mature presenilin 2 increases the leakage of intracellular calcium stores: Specific mechanisms and targets.
No full textBackground. We have previously shown that fibroblasts from FAD patients carrying mutations in either PS1 (M146L, P117L) or PS2 (M239I, T122R) showed a reduced instead of an exaggerated calcium release from intracellular stores (1-3). These and other PS1/2 mutants (PS1-A246E, PS1-L286V, PS2-N141I), as well as the wild type (wt) forms of these proteins share the same feature when transiently over-expressed in different cell lines and rat primary neurons. Whereas PS1 mutants cause modest reductions under transient expression, PS2 mutants dramatically reduce the store calcium content. Accordingly, the latter also cause lower steady-state calcium concentrations at the level of the endoplasmic reticulum (ER) and Golgi apparatus (3).
Methods. By employing both Fura-2 and organelle-targeted aequorins to monitor calcium concentrations in the cytosolic and the lumen, we here investigate in HeLa, SH-SY5Y and MEFs - either wt or devoid of endogenous PSs (DKO MEFs) – the mechanisms by which PS2 variants alter store calcium handling.
Results. We provide evidence that: i) expression of wt or mutant PS2 reduces the store calcium content both by increasing the ER calcium leakage and by reducing the ER calcium uptake by SERCA pumps; ii) the full-length (FL) but not the mature form of the protein is directly involved in store calcium handling; iii) the effect is completely independent of -secretase activity since it is not rescued by pre-incubation with enzyme inhibitors or by expression of a loss-of-function mutant (PS2-D366A); iv) the ryanodine receptor and the ribosome translocon complex are not directly involved. Whether FL PS2 variants represent by themselves a leakage pathway (4) or whether their effect is mediated by IP3 receptors is now under investigation.
Conclusions. We suggest that, at variance with the majority of FL PS1 mutants that leave unchanged or even overload intracellular calcium stores, making the cells more susceptible to toxic stimuli, FL PS2 mutants, by lowering ER/Golgi calcium levels result in a less aggressive FAD phenotypes.
1.Giacomello et al., Neurobiology of Disease 18, 638-648, 2005.
2. Zatti et al., Neurobiology of Disease 15, 269-278, 2004.
3. Zatti et al., Cell Calcium 39, 539-550, 2006.
4. Tu et al. Cell 126, 981-993, 2006
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
Presenilin-2 dampens intracellular Ca2+ stores by increasing Ca2+ leakage and reducing Ca2+ uptake.
Full text linkWe have previously shown that familial Alzheimer's disease mutants of presenilin-2 (PS2) and, to a lesser extent, of presenilin-1 (PS1) lower the Ca(2+) concentration of intracellular stores. We here examined the mechanism by which wild-type and mutant PS2 affect store Ca(2+) handling. By using HeLa, SH-SY5Y and MEFs as model cells, and recombinant aequorins as Ca(2+) probes, we show evidence that transient expression of either wild-type or mutant PS2 increases the passive Ca(2+) leakage: both ryanodine- and IP(3)-receptors contribute to Ca(2+) exit out of the ER, whereas the ribosome translocon complex is not involved. In SH-SY5Y cells and MEFs, wild-type and mutant PS2 potently reduce the uptake of Ca(2+) inside the stores, an effect that can be counteracted by over-expression of SERCA-2B. On this line, in wild-type MEFs, lowering the endogenous level of PS2 by RNA interference, increases the Ca(2+)-loading capability of intracellular stores. Furthermore, we show that in PS double knockout MEFs, reduction of Ca(2+) stores is mimicked by the expression of PS2-D366A, a loss-of-function mutant, uncleaved because also devoid of presenilinase activity but not by co-expression of the two catalytic active fragments of PS2. In summary, both physiological and increased levels of wild-type and mutant PS2 reduce the Ca(2+) uptake by intracellular stores. To exert this newly described function, PS2 needs to be in its full-length form, even if it can subsequently be cleaved
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
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
- …
