1,720,977 research outputs found
Remodeling in acute coronary syndromes: expectations and frustrations for risk assessment and therapy.
No full textMatrix metalloproteinases are involved in the development of acute coronary syndromes, but they are not reliable clinical markers of the occurrence or the outcome of this syndrome. Many limitations in their assessment account for such failure. Functional genetic polymorphisms, as alternatives to plasma levels, might be an interesting alternative
L’approccio read-through per il trattamento della fibrosi cistica causata da mutazioni di stop Durata: 24 mesi (dal 01/09/2012 al 31/08/2014) Progetto n°: 01/2012 FFC Finanziato da: Fondazione per la Ricerca sulla Fibrosi Cistica-Bando 2012
No full textDurata: 24 mesi (dal 01/09/2012 al 31/08/2014)
Progetto n°: 01/2012 FFC
Finanziato da: Fondazione per la Ricerca sulla Fibrosi Cistica-Bando 2012-Nonsense mutations are the leading cause of approximately 30% of inherited diseases, including cystic fibrosis (CF). They promote premature translational termination and following loss of CFTR protein by introduction of premature termination codons (PTCs). In the last few years, it has been demonstrated that drugs (like aminoglycoside antibiotics) can be designed and produced to suppress this process by the ribosomal read-through mechanism where these drugs mask PTC synthetizing a full-lengh CFTR protein. The rationale supporting of this project is to optimize the ribosomal read-through molecules leading to restoration of CFTR production in cystic fibrosis caused by stop mutation. This study may introduce new hopes for the development of a pharmacologic approach to the cure of CF
Novel cellular model system and therapeutic molecules for the development of a read-through approach for CF caused by stop codon mutations of the CFTR gene-Progetto n°: 02/2010 FFC Finanziato da: Fondazione per la Ricerca sulla Fibrosi Cistica-Bando 2010 Durata: 12 mesi (dal 01/09/2010 al 31/08/2011)
No full textProgetto n°: 02/2010 FFC
Finanziato da: Fondazione per la Ricerca sulla Fibrosi Cistica-Bando 2010
Durata: 12 mesi (dal 01/09/2010 al 31/08/2011)- Nonsense mutations promote premature translational termination and are the leading cause of approximately 30% of inherited diseases, including cystic fibrosis. In the last few years, it has been demonstrated that drugs (like 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 provide a mean of restoring CFTR function in patients with stop mutations and have introduced new hopes for the development of a pharmacologic approach to the cure of CF. The rationale supporting this project is to optimize the read-through molecules leading to restoration of CFTR production in cystic fibrosis caused by non-sense stop codon mutations. The objectives of this project are: development of in vitro cellular model systems and biochemical screening systems; synthesis of novel drugs exhibiting read-through effects on CFTR mRNA carrying stop codon mutations; development of experimental strategies to reduce NMD of the CFTR mRNA and biological assays on treated experimental model systems, testing the activity of the read-through drugs on CFTR function of chloride transport
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Screening Readthrough Compounds to Suppress Nonsense Mutations: Possible Application to β-Thalassemia
Get PDFSeveral types of thalassemia (including beta(0)39-thalassemia) are caused by nonsense mutations in genes controlling globin production, leading to premature translation termination and mRNA destabilization mediated by the nonsense mediated mRNA decay. Drugs (for instance, aminoglycosides) can be designed to suppress premature translation termination by inducing readthrough (or nonsense suppression) at the premature termination codon. These findings have introduced new hopes for the development of a pharmacologic approach to cure this genetic disease. In the present review, we first summarize the principle and current status of the chemical relief for the expression of functional proteins from genes otherwise unfruitful for the presence of nonsense mutations. Second, we compare data available on readthrough molecules for beta(0)-thalassemia. The examples reported in the review strongly suggest that ribosomal readthrough should be considered as a therapeutic approach for the treatment of beta(0)-thalassemia caused by nonsense mutations. Concluding, the discovery of molecules, exhibiting the property of inducing beta-globin, such as readthrough compounds, is of great interest and represents a hope for several patients, whose survival will depend on the possible use of drugs rendering blood transfusion and chelation therapy unnecessary
Variations on the Author
Get PDF“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
Get PDFWe 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
Coagulation indicators in patients with paroxysmal atrial fibrillation: Effects of electric and pharmacologic cardioversion.
No full textThe aim of this study was to determine whether paroxysmal atrial fibrillation (PAF) and/or restoration to sinus rhythm with
electric or pharmacologic cardioversion induce modifications to the coagulation system. Thirty-five patients with PAF undergoing
either electric (n = 11) or pharmacologic (n = 24) cardioversion were studied. Fibrinopeptide A and D-dimer blood
samples were taken immediately before and after cardioversion at different intervals. When compared with the control
group (n = 70), the precardioversion fibrinopeptide A plasma values were significantly elevated (11.8 vs 2.5 ng/mL). Fibrinopeptide
A plasma values were significantly reduced 5 minutes after cardioversion (11.8 vs 5.3 ng/mL) and remained stable
throughout the follow-up sequential measurements. D-dimer plasma values were significantly increased (measured at 12
hours and at day 7) in patients who underwent electrical cardioversions only. A positive correlation (R2 = 0.76) was found
between the energy delivered for cardioversion to sinus rhythm and D-dimer plasma values on day 7. In patients with PAF,
levels of fibrinopeptide A, an indicator of coagulation activation, are elevated and soon reduced by the restoration of sinus
rhythm. Electric, but not pharmacologic, cardioversion induces an early activation of the fibrinolytic system
Body composition and muscular strength changes after moderate activity: association with matrix metalloproteinase polymorphisms.
No full textRemodeling of skeletal muscles is regulated by matrix metalloproteinases (MMPs). Functional genetic polymorphism (PM), modulating the expression of some MMPs, might be associated to different body composition and muscular strength improvement after exercise.
Genetic PM of MMP-1 (G+/- at -1607), MMP-3 (5A/6A at -1171) and MMP-9 (Cytosine- Adenine microsatellite = 13-27CA) repeats, around -90), body cell mass (BCM), extracellular water (ECW) and isometric maximal extensor strength (MES) of both legs were determined in 17 old sedentary women at the beginning and at the end of a 24 week physical exercise program. A 12 and 72% increase in BCM and MES, respectively, and 11% reduction in ECW were observed at the end of the program. Carriers of G-insertion in MMP-1, PM increased their BCM (7 kg vs. -1.5, P = 0.007) and lost ECW (9% of total body water vs. 0.1%, P = 0.004) more than the non-carriers; homozygote for 21 or less CA repeats/allele in MMP-9 PM gained more MES (115 N, interquartile range = IQR = 63-132) than carriers of longer microsatellites (63 N, IQR = 40-86, P = 0.028). MMP-3 did not show any association with body composition and exercise-related strength changes. Exercise in elderly women increases BCM and strength, these changes are associate to specific MMP genotypes
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