1,721,013 research outputs found
Role of the Mitochondrial E3 Ubiquitin Ligases as Possible Therapeutic Targets in Cancer Therapy
No full textUbiquitination is a post-translational modification that targets specific proteins on their lysine residues. Depending on the type of ubiquitination, this modification ultimately regulates the stability or degradation of the targeted proteins. Ubiquitination is mediated by three different classes of enzymes: the E1 ubiquitin-activating enzymes, the E2 ubiquitin-conjugating enzymes and, most importantly, the E3 ubiquitin ligases. E3 ligases are responsible for the final step of the ubiquitin cascade, interacting directly with the target proteins. E3 ligases can also be involved in DNA repair, cell cycle regulation and response to stress; alteration in their levels can be involved in oncogenic transformation and cancer progression. Of all the six hundred E3 ligases of the human genome, only three of them are specific to the mitochondrion: MARCH5, RNF185 and MUL1. Their alterations (that reflect on the alteration of the mitochondria functions) can be related to cancer progression, as underlined by the increasing research performed in recent years on these three mitochondrial enzymes. This review will focus on the function and mechanisms of the mitochondrial E3 ubiquitin ligases, as well as their important targets, in cancer development and progression, also highlighting their potential use for cancer therapy
Up-regulation of pro-angiogenic pathways and induction of neovascularization by an acute retinal light damage.
Full text linkThe light damage (LD) model was mainly used to study some of the main aspects of age related macular degeneration (AMD), such as oxidative stress and photoreceptor death. Several protocols of light-induced retinal degeneration exist. Acute light damage is characterized by a brief exposure (24 hours) to high intensity light (1000 lux) and leads to focal degeneration of the retina which progresses over time. To date there are not experimental data that relate this model to neovascular events. Therefore, the purpose of this study was to characterize the retina after an acute light damage to assess whether the vascularization was affected. Functional, molecular and morphological investigations were carried out. The electroretinographic response was assessed at all recovery times (7, 60, 120 days after LD). Starting from 7 days after light damage there was a significant decrease in the functional response, which remained low up to 120 days of recovery. At 7 days after light exposure, neo-vessels invaded the photoreceptor layer and retinal neovascularization occurred. Remarkably, neoangiogenesis was associated to the up-regulation of VEGF, bFGF and their respective receptors (VEGFR2 and FGFR1) with the progression of degeneration. These important results indicate that a brief exposure to bright light induces the up-regulation of pro-angiogenic pathways with subsequent neovascularization
Protect and counter-attack: nutritional supplementation with essential amino acid ratios reduces doxorubicin–induced cardiotoxicity in vivo and promote cancer cell death in vitro
No full textGenomic organization and cytokine-mediated inducibility of the human TRIM-8/GERP gene.
No full textCytokine signaling is negatively regulated by a set of SH2 domain-containing proteins, the Suppressors of Cytokine Signaling (SOCS) acting as intracellular modulators. Experimental evidence indicates that SOCS gene expression is induced by cytokines and pro-inflammatory stimuli and is highly controlled both at transcription and translation level. Furthermore, SOCS proteins appears rapidly degraded inside the cells, mostly controlling their stability by interacting with specific molecules such as elongin B and C. It has been shown that SOCS-1/JAB, a member of the SOCS family interacts with TRIM-8/Gerp, a new ring protein specifically binding SOCS-1 recombinant polypeptide in vitro and in vivo. TRIM-8/Gerp, transcribes a 3.0Kb mRNA, spans 551 AA and is highly conserved during evolution. In addition, it can be induced by IFN-gamma in epithelial and lymphoid cells and is expressed mostly ubiquitously in murine and human tissues. Here in this report we present the genomic organization of this new SOCS-1 interactor and we add new tools for extending investigation of the complex mechanism that undergoes negatively regulation of cytokine signaling
Nanoceria protect retinal pigment epithelium in the light damaged retina
No full textPurpose : Dry age-related macular degeneration (AMD) is the most common form of AMD, characterized by retinal pigment epithelium (RPE) dysfunction and death, associated to lipofuscin accumulation, photoreceptors death, autophagy alterations and vision loss. Despite its frequency, only palliative therapies are available. In order to search for improvements we investigated the development of the dry AMD in the light damaged (LD) model and tested the protective effects of cerium oxide nanoparticles (nanoceria).
Methods : The dry features of AMD were investigated on Sprague Dawley albino rats exposed to bright light (1000 lux) for 3h, 6h, 9h, 12h, 24h and for 24h followed by 3 and 7 days of recovery, then compared to the healthy controls. The treatment was performed by nanoceria intravitreal injection (2 μl [1mM]) in both eyes 3 days before light exposure (for 24h). After 7 days from injury treated and untreated animals were compared. Oxidative stress was evaluated by acrolein fluorescence intensity on immunolabeled retinal cryosections and RPE was pointed out by anti-RPE65 immunofluorescence. Lipofuscin quantitation was performed by ImageJ software on retinal whole mounts images acquired by confocal microscopy. Autophagy was analysed by LC3B-II western blot.
Results : The RPE was disrupted in the dorsal retina of LD rats starting 3 days after injury. LCB3-II was significantly increased after 24h of light exposure (p<0,05) and remained up-regulated after 7 days of recovery (p<0,05). We also observed lipofuscin accumulation over time and increased oxidative stress already detectable after 7 days of recovery. By nanoceria treatment oxidative stress was significantly reduced in the outer nuclear layer (p<0,01) and in the RPE (p<0,05) of the treated group. Accordingly the blood-retinal barrier was intact since the RPE was not affected and lipofuscin was significantly reduced in terms of number of granules (p<0,001) and percentage of occupied area (p<0,001). LCB3-II was down-regulated in the nanoceria-treated animals compared to the untreated ones (p<0,001).
Conclusions : Our study demonstrates that cerium oxide nanoparticles protect the RPE and limit the dry features of AMD in the light-damaged model. On this basis we propose nanoceria as a new potential therapeutic agent for the dry form of AMD
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
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