1,721,002 research outputs found
Tobramycin inhibits interleukin-8 gene expression and acts as suppressor of premature termination codons in the absence of NMD
No full textAminoglycosides are widely used for the treatment of cystic fibrosis (CF), a fatal, autosomal, recessive genetic disease characterized by persistent pulmonary infection and extensive lung inflammation. In addition to their role as antibiotics, aminoglycosides have been shown to act as suppressors
of nonsense mutations that generate premature translation termination (PTCs). PTCs constitute the molecular basis of many genetic diseases, including CF (5-10% of cystic fibrosis alleles contain PTCs) as lead to the synthesis of truncated non-functional or partially functional protein. Suppression of translation terminations at PTCs (read-through) has been
developed as a therapeutic strategy to restore full-lenght protein in several genetic diseases. Phenotypic consequences of PTCs can be exacerbated by the nonsense-mediated mRNA decay (NMD) pathway that detect and degrade PTC containing mRNA. Modulation of NMD, therefore, is also of interest as a potential target for the suppression therapy. Tobramycin
is an aminoglycoside antibiotic, normally used to treat Pseudomonas aeruginosa pulmonary infection in CF patients. In the present study we have investigated, on one hand, the properties of Tobramycin as a modulator of the expression of IL-8 associated with inflammation of the CF airway pathology in CF IB3-1 cells induced with pro-inflammatory cytokine TNF-
α. On the other hand, by using the yeast as a genetic system, we have examined the ability of Tobramycin to suppress PTCs as a function of the presence or absence of NMD. Results demonstrate that Tobramycin is a good inhibitor of IL-8 expression and exhibits read-through ability on PTCs in conditions in which NMD is not operating in the cell
Therapeutic molecules for the development of a read-through approach for diseases caused by nonsense mutations
No full textNonsense mutations lead to premature translational termination and mRNA destabilization through nonsense-mediated RNA decay. These mutations rise to premature translation termination codons (PTTCs) within the coding region of mRNAs and are the cause of approximately 30% of inherited diseases, including thalassemia and cystic fibrosis. Premature arrest of translation may involve the synthesis of truncated abnormal proteins that can be toxic to target cells through dominant negative or gain-of-function effects. The functional consequences of nonsense mutations are further affected by the nonsense-mediated RNA decay, a cellular mechanism aimed to detect and degrade PTTCs containing mRNAs. In the last few years, it has been demonstrated that drugs (such as aminoglycoside antibiotics) can be designed and produced to suppress premature translation termination, inducing a ribosomal read-through of premature, but not normal termination codons. Moreover, the treatments with aminoglycosides may restore the loss function in patients with nonsense mutations and have introduced new hopes for the development of a pharmacologic approach of these diseases
The Saccharomyces cerevisiae OXA1 gene is required for the correct assembly of cytochrome c oxidase and oligomycin-sensitive ATP synthase.
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Permeabilidad al amoníaco de la aquaporina-8 de rata (rAQP8) expresada en mitocondrias de levadura
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Spectrophotometric determination with hemoglobin of the rate of oxygen consumption in mitochondria.
No full textGoing 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
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