1,721,113 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
Variability of HXT2 at the protein and gene level among the Saccharomyces sensu stricto group
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Invasive listeriosis in a patient with several episodes of antibiotic associated colitis presumably due to Clostridium difficile
No full textA 62-year-old man developed a blood stream infection and meningitis due to Listeria monocytogenes, 20 days after an episode of pseudo-membranous colitis. The patient, hospitalized for the first time for transurethral prostatectomy, was readmitted 20 days later with watery diarrhea. Pseudo-membranous colitis was diagnosed and treated successfully, without testing for Clostridium difficile infection (CDI). After 15 more days, the patient developed again diarrhea, fever and confusion. Hospitalized again, blood and cerebrospinal fluid cultures resulted positive for L. monocytogenes. The patient was treated successfully and a diagnosis of recurrent CDI was confirmed following culture and nucleic acid amplification assays both positive for C. difficile. This is the first report of an invasive listeriosis after CDI underlines the importance of taking greater awareness in complicated blood stream infections that may arise after CDI
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
Critical observations on computerized analysis of banding patterns with commercial software packages
No full textAccurate Analytical Thermal Model of the Heating Element in Micromachined Gas Sensors
No full textIn this paper, a simple analytical model of the steady -state thermal behavior of a Pt microheater for micromachined gas sensors is presented. It is demonstrated that simple resistance vs. power measurements, coupled with a suitable thermal model, are sufficient for a precise determination of the sensor temperature
Bio-based building components: A newly sustainable solution for traditional walls made of Arundo donax and gypsum
Full text linkTo contribute to the use of bio-based materials in the building sector, a novel bio-based wall panel, with a high thermal performance level, is proposed in this work. The panel is based on an ancient rural technique, widely diffused in southern Italy, which makes use of Arundo donax L. canes combined with gypsum plaster to build walls and ceilings of rural buildings. The enhancement of the thermal capacity of these panels by means of the introduction in the canes of a natural wax oleogel (WO) is proposed in this paper. A specific experimental campaign aiming at the comparison of traditional and innovative panels was carried out to assess the enhanced thermal performance of the proposed solution. The maximum value of heat flow absorbed from the panel with WO was 61.08 W/m(2) around a mean panel temperature of 24 & DEG;C, corresponding to the melting temperature range of the WO. The panel without WO at the same temperature absorbed an incoming heat flow of 34.64 W/m(2) which is about 57% of the panel with WO. The panel with WO released at a temperature of about 27.5 & DEG;C, a heat flow of 43.42 W/m(2). At the same temperature of about 27.5 & DEG;C, the panel without WO released a heat flow of 34.38 W/m(2) which is about 80% that of the panel with WO. The results highlighted that the addition of natural WO has enhanced the thermal capacity of the panel facilitating heat dissipation through the borders. These characteristics make the panel a suitable component for internal partitions of controlled temperature zones such as residential rooms, storage food areas, livestock buildings, and where it is necessary to obtain a constant environmental temperature. In particular, the null or low toxicity of the panel's materials allows for partition use, also in hygienically safe environments
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