1,721,017 research outputs found
ETF dehydrogenase advances in molecular genetics and impact on treatment
No full textElectron transfer flavoprotein dehydrogenase, also called ETF-ubiquinone oxidoreductase (ETF-QO), is a protein localized in the inner membrane of mitochondria, playing a central role in the electron-transfer system. Indeed, ETF-QO mediates electron transport from flavoprotein dehydrogenases to the ubiquinone pool. ETF-QO mutations are often associated with riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (RR-MADD, OMIM#231680), a multisystem genetic disease characterized by various clinical manifestations with different degrees of severity. In this review, we outline the clinical features correlated with ETF-QO deficiency and the benefits obtained from different treatments, such as riboflavin, L-carnitine and/or coenzyme Q10 supplementation, and a diet poor in fat and protein. Moreover, we provide a detailed summary of molecular and bioinformatic investigations, describing the mutations identified in ETFDH gene and highlighting their predicted impact on enzymatic structure and activity. In addition, we report biochemical and functional analysis, performed in HEK293 cells and patient fibroblasts and muscle cells, to show the relationship between the nature of ETFDH mutations, the variable impairment of enzyme function, and the different degrees of RR-MADD severity. Finally, we describe in detail 5 RR-MADD patients carrying different ETFDH mutations and presenting variable degrees of clinical symptom severity
Stable expression of antisense urokinase mRNA inhibits the proliferation and invasion of human hepatocellular carcinoma cells
No full textInduction of fibronectin mRNA by urokinase- and tissue-type plasminogen activator in human skin fibroblasts: differential role of u-PA and t-PA at FN protein level
No full textTherapies currently in phase II trials for malignant pleural mesothelioma
No full textIntroduction: Malignant pleural mesothelioma (MPM) is an aggressive cancer
associated with asbestos exposure, whose incidence will peak within the next
years. Despite an overall low response rate, the current first-line therapy is
represented by combined chemotherapy with cisplatin and antifolate. Moreover,
there are no currently approved regimens for relapsed or refractory
MPM. Therefore, it is clear how both preclinical and clinical researches aimed
at identifying new therapeutic targets and testing them in early clinical
settings are badly needed.
Areas covered: The aim of this review is to summarize and critically comment
the ongoing Phase II trials for MPM.
Expert opinion: Over the past few years, there has been a significant endeavor
of addressing the clinical research for MPM beyond the very modest results of
chemotherapy. Nonetheless, our understanding is that the treatment of MPM
should not be merely ‘copied’ from that of other much better studied tumors.
In the light of recent results, studies toward the metabolic characteristics of
this tumor are being progressively addressed. These evidences are disclosing
a rather unusual model of malignancy, very likely to be more sensitive to
novel ‘MPM cells- and microenvironment-tailored’ therapy addressing these
characteristics rather than the sole cancer proliferatio
Metabolic lipid muscle disorders: biomarkers and treatment
No full textLipid storage myopathies (LSMs) are metabolic disorders of the utilization of fat in muscles due to several different defects. In this review, a molecular update of LSMs is presented and recent attempts of finding treatment options are discussed. The main topics discussed are: primary carnitine deficiency, riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency, neutral lipid storage disorders and carnitine palmitoyl transferase deficiency. The most frequent presentations and genetic abnormalities are summarized. We present their diagnosis utilizing biomedical and morphological biomarkers and possible therapeutic interventions. The treatment of these metabolic disorders is a subject of active translational research but appears, in some cases, still elusive
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
Quantitative in situ hybridization for the evaluation of gene expression in asynchronous and synchronized cell cultures and in tissue sections
Full text linkWe describe an image analysis (IA) system that has been applied for the quantitative evaluation of mRNAs evidenced by in situ hybridization (ISH) with radiolabelled probes in cultured cells and in tissue sections. The ISH-IA method was used for the evaluation of cultured cell morphological parameters such as cell and nucleous area (CA and NA, respectively) in parallel with the levels of mRNAs detected as hybridization grains areas (GA). The evaluation of these parameters, together with the analysis of the levels of mRNAs (c-jun, cyclin A) specific for given cell cycle phases (i.e. G1 and S/G2), allowed the identification, in asynchronous cultures of human skin fibroblasts, of cells in G1 and S/G2 phases. The mRNA levels measured by ISH-AI were comparable with those detected by RT-PCR. This method was also applied for the analysis of fibronectin (FN) gene expression in control skin fibroblasts in relationship with the different phases of the cell cycle and in comparison with a tumor cell line (Sk-Hep1), heterogeneous either for morphometric parameters or for the levels of this transcript. Finally, the ISH-AI was applied for the semiquantitative evaluation of the expression, localization and alternative splicing pattern of FN mRNA in normal liver and in hepatocellular carcinoma (HCC) tissue sections
u-PA and c-MET mRNA expression is co-ordinately enhanced while hepatocyte growth factor in RNA is down regulated in human hepatocellular carcinoma
No full textVariations 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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