1,721,014 research outputs found
NBS1 regulates primary ciliogenesis altering actin/tubulin dynamics: implications for the Nijmegen Breakage Syndrome
No full textGenome integrity must be preserved for the correct propagation of the genetic information. To safeguard this, cells have evolved repair pathways, collectively known as the DNA Damage Response (DDR). Mutations in NBS1, a subunit of the MRE11/RAD50/NBS1 (MRN) complex, lead to the DDR-defective Nijmegen Breakage Syndrome (NBS), a rare human autosomal recessive disorder. The clinical manifestations of NBS are microcephaly, neurological abnormalities, immunodeficiency, growth retardation, and ultimately cancer predisposition. Microcephaly is a common outcome of genetic defects involving proteins of the centrosome and primary cilium (PC). This non-motile solitary organelle protrudes from the surface of all mammalian cells. Importantly, the centrosome converts into the basal body (BB) to enucleate the PC during the G0/G1 and regulates cytoskeleton dynamics to control PC length. Therefore, PC and DDR-related pathways converge in regulating neuronal progenitor cells (NPCs). Recently, we demonstrated that NBS1 depletion induces striking elongation and dysmorphisms of the PC in multiple cell models, coupled with defects in the Shh pathway, a PC-dependent mitogenic neurodevelopmental pathway involved in the proliferation and survival of NPCs. Given that, we speculated the existence of functional relationships between NBS1 and the Primary Cilium that might be responsible for the neurological phenotype observed in NBS.
In this study we evaluated: i) whether NBS1 depletion alters PC protein trafficking and Shh-pathway regulators; ii) the molecular mechanism through which NBS1 regulates the PC and iii) whether the most common hypomorphic mutation of the NBN gene, found in NBS patients, affects the PC. Our results demonstrated that NBS1-depleted cells have alterations of PC protein trafficking correlated with alterations of GliA/GliR ratio. We showed that the PC phenotype induced by NBS1 depletion is associated with alterations of the actin/tubulin dynamics, remarkably similar to that caused by cytochalasin D (CD), a strong inhibitor of actin polymerization. Indeed, treatments with CD did not further lengthen the PC in NBS1-depleted cells, suggesting that NBS1KO and CD may act through the same molecular mechanism/s. In addition, we demonstrated that the PC phenotype due to NBS1 depletion was counteracted by the exhaustion of soluble tubulin induced by Taxol. Coherently, CD impacted PC protein trafficking and the Shh pathway similarly to what was observed following the depletion of NBS1. Finally, we observed a significant increase in the PC length in human fibroblasts derived from an NBS patient (GM7166) compared to healthy controls, coupled with alterations both in PC protein trafficking and cytoskeleton dynamics.
Overall, our data provide crucial insights into the role of NBS1 on the molecular mechanisms involved in PC regulation, opening a possible reclassification of the NBS among the ciliopathies. Additionally, these results may contribute to explaining why genetic defects in centrosome/PC and DDR proteins may lead to the same neuronal phenotype
Serum lactate dehydrogenase as early marker of posterior reversible encephalopathy syndrome: keep your eyes open.
No full textEnd-of-life: still an Italian dilemma
No full textIn Italy the debate on the end-of-life scenario is still in progress. Many political and religious personalities or associations have expressed a wide range of opinions
Posterior reversible encephalopathy syndrome (PRES) in the parturient with preeclampsia after inadvertent dural puncture
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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
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