1,720,976 research outputs found
Proteomics of osteosarcoma
No full textOsteosarcoma (OS) is the most common primary malignant tumor of bone and the third most common cancer in childhood and adolescence. Nowadays, early diagnosis, drug resistance and recurrence of the disease represent the major challenges in OS treatment. Post-genomics, and in particular proteomic technologies, offer an invaluable opportunity to address the level of biological complexity expressed by OS. Although the main goal of OS oncoproteomics is focused on diagnostic and prognostic biomarker discovery, in this review we describe and discuss global protein profiling approaches to other aspects of OS biology and pathophysiology, or to investigate the mechanism of action of chemotherapeutics. In addition, we present proteomic analyses carried out on OS cell lines as in vitro models for studying osteoblastic cell biology and the attractive opportunity offered by proteomics of OS cancer stem cells
Treatment of alkaptonuria and tyrosinemia type I
No full textThe present invention relates to a compound of formula (I) or (Π) for use in the prevention and/or treatment of a dis - ease characterized by the accumulation of HGA or of succinyl acetoacetate and succinylacetone: The present invention also relates to compositions comprising such compounds
Oxidative damage mediated by herbicides on yeast cells
No full textAgricultural herbicides are among the most commonly used pesticides worldwide, posing serious concerns for both humans, exposed to these chemicals through many routes, and the environment. To clarify the effects of three herbicides as commercial formulations (namely, Pointer, Silglif, and Proper Energy), parameters related to oxidative issues were investigated on an autochthonous wine yeast strain. It was demonstrated that herbicides were able to affect the enzymatic activities of catalase and superoxide dismutase, as well as to induce carbonylation and thiol oxidation as post-translational modifications of proteins. Saccharomyces cerevisiae is an optimal model system to study responses to xenobiotics and oxidative stress. Thus, the results obtained could further the understanding of mechanisms underlying the toxicity of herbicides
Comparative proteomics in alkaptonuria provides insights into inflammation and oxidative stress
No full textAlkaptonuria (AKU) is an ultra-rare inborn error of metabolism associated with a defective catabolism of phenylalanine and tyrosine leading to increased systemic levels of homogentisic acid (HGA). Excess HGA is partly excreted in the urine, partly accumulated within the body and deposited onto connective tissues under the form of an ochronotic pigment, leading to a range of clinical manifestations. No clear genotype/phenotype correlation was found in AKU, and today there is the urgent need to identify biomarkers able to monitor AKU progression and evaluate response to treatment. With this aim, we provided the first proteomic study on serum and plasma samples from alkaptonuric individuals showing pathological SAA, CRP and Advanced Oxidation Protein Products (AOPP) levels. Interesting similarities with proteomic studies on other rheumatic diseases were highlighted together with proteome alterations supporting the existence of oxidative stress and inflammation in AKU. Potential candidate biomarkers to assess disease severity, monitor disease progression and evaluate response to treatment were identified as well
Proteomics and redox-proteomics of the effects of herbicides on a wild-type wine Saccharomyces cerevisiae strain
No full textSeveral toxicological and environmental problems are associated with the extensive use of agricultural pesticides, such as herbicides. Nevertheless, little is known about the toxic effects of formulated herbicides, since many studies have been carried out using pure active molecules alone. In this work, we used as an eukaryotic model system an autochthonous wine yeast strain to investigate the effects of three commercial herbicides, currently used in the same geographical area from where this strain had been isolated. We carried out a comparative proteomic analysis to study the effects at the protein level of the herbicide-related stress, and found that the herbicides tested can alter the yeast proteome producing responses that share homologies with those observed treating yeast cells with the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) or with well-known oxidizing agents. We evaluated, through redox-proteomic techniques, protein carbonylation as a biomarker of oxidative stress. This analysis showed that herbicide-induced carbonylation is a dynamic phenomenon with degrees of selectivity
Inhibition of para-Hydroxyphenylpyruvate Dioxygenase by Analogues of the Herbicide Nitisinone As a Strategy to Decrease Homogentisic Acid Levels, the Causative Agent of Alkaptonuria
No full textAlkaptonuria (AKU) is a rare multisystem metabolic disease caused by deficient activity of homogentisate 1,2-dioxygenase (HGD), which leads to the accumulation of homogentisic acid (HGA). Currently, there is no treatment for AKU. The sole drug with some beneficial effects is the herbicide nitisinone (1), an inhibitor of p-hydroxyphenylpyruvate dioxygenase (4-HPPD). 1 has been used as a life-saving drug in infants with typeI tyrosinemia despite severe side effects due to the buildup of tyrosine. Four clinical trials of nitisinone to treat AKU have shown that 1 consistently decreases HGA levels, but also caused the accumulation of tyrosine in blood serum. Moreover, the human preclinical toxicological data for 1 are incomplete. In this work, we performed pharmacodynamics and toxicological evaluations of 1, providing the first report of LD50 values in human cells. Intracellular tyrosinemia was also evaluated. Three additional 4-HPPD inhibitors with a more favorable profile than that of 1 in terms of IC50, LD50, and tyrosine accumulation were also identified among commercially available compounds. These may be promising starting points for the development of new therapeutic strategies for the treatment of AKU. A better stop 4-HPPD: Alkaptonuria (AKU) is a rare and serious multisystem debilitating disease with no licensed treatment. Nitisinone is used to treat AKU despite severe hypertyrosinemia and incomplete preclinical human toxicological data. This study provides the first determinations of LD50 values in human cells and suggests the use of alternative compounds as promising scaffolds for developing new therapeutic strategies for treatment of AKU
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
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