1,720,960 research outputs found
PTRH2 as a checkpoint of mitochondrial induced-apoptosis in Cancer and Neurodegeneration
No full textI mitocondri sono strutture intracellulari in grado di decodificare una varietà di stimoli extracellulari, che vanno dalla produzione di energia alla morte cellulare. Quando l'omeostasi del Ca2+ mitocondriale è compromessa, possono verificarsi condizioni patologiche molto diverse, dal cancro alle malattie neurodegenerative, a seconda del tipo di cellula e del pathway molecolare coinvolto. Durante il mio dottorato, ho cercato di fare luce sul meccanismo molecolare attraverso il quale PTRH2, una proteina mitocondriale, regola la sopravvivenza e la morte cellulare sia in neuroblastoma che nelle malattie neurodegenerative. PTRH2 è un protettore dell'apoptosi indotta da stress nelle cellule aderenti. L'attività pro-survival di PTRH2 è stata attribuita ai suoi effetti sui mitocondri, tuttavia il meccanismo d’azione resta ancora sconosciuto. I pazienti con una mutazione germinale omozigote PTRH2 (PTRH2DF) sviluppano una malattia neurologica multisistemica infantile caratterizzata da microcefalia postnatale, atrofia cerebellare progressiva e malattia neurodegenerativa (IMNPED). Le cellule con bassi livelli di espressione di PTRH2 o quelle da pazienti con PTRH2DF mostrano una maggiore sensibilità all'apoptosi indotta da stress, mentre le cellule con alti livelli di espressione di PTRH2 sono resistenti alla morte indotta da stimoli apoptotici. In questo progetto, ho dimostrato che un'elevata espressione di PTRH2 nei tumori dei pazienti con neuroblastoma (NB) è correlata a prognosi sfavorevole, con sviluppo di metastasi allo stadio 4, livelli di Ca2+mitocondriale bassi e resistenza al trattamento chemioterapico. Al contrario, cellule di NB che esprimono poco o mancano di PTRH2 mostrano un elevato Ca2+ mitocondriale e una risposta apoptotica migliorata al trattamento chemioterapico. In questo lavoro, dimostriamo che PTRH2 modula, interagendo con la deubiquitinasi Trabid, l'espressione proteica di mt-ND5, subunità del complesso I mitocondriale. Pertanto, PTRH2 stabilizza l'attività di mt-ND5 modulando i flussi di Ca2+ e i livelli di ATP nei mitocondri e proteggendo le cellule dallo stress indotto apoptosi. Proponiamo che PTRH2 sia un gatekeeper mitocondriale, per cui la perdita di PTRH2 provoca sovraccarico di Ca2+ mitocondriale e morte cellulare che porta a sviluppo di malattie neurodegenerative. Al contrario, un'elevata espressione di PTRH2 induce un basso assorbimento mitocondriale di Ca2+ promuovendo la resistenza alla morte cellulare e allo sviluppo del tumore. I nostri dati forniscono un razionale meccanicistico per la capacità del PTRH2 di regolare l'apoptosi indotta dai mitocondri e forniscono un nuovo punto di partenza per future indagini volte a identificare nuove terapie per e contro la morte cellulare mediata dai mitocondri.Mitochondria are structures within the cells able to decode a variety of extracellular stimuli into greatly different intracellular actions, ranging from energy production to cell death. When mitochondrial Ca2+ homeostasis is compromised, very different pathological conditions can occur, from cancer to neurodegenerative diseases, depending on the cell type and pathway involved.
During my Phd, I tried to shed light on the molecular mechanism by which PTRH2, a mitochondrial protein, regulates cell-survival and death both in cancer and in neurodegenerative disease. PTRH2 is a protector of stress-induced apoptosis in adherent cells. The pro-survival activity of PTRH2 has been attributed to its effects at the mitochondria by an unknown mechanism. Patients with an inherited homozygous germ line PTRH2 mutation (PTRH2DF) develop infantile multisystem neurologic disease characterized by postnatal microcephaly, progressive cerebellar atrophy and neurodegenerative disease (IMNPED). Cells with reduced PTRH2 levels or PTRH2DF patient cells exhibit increased sensitivity to stress-induced apoptosis whereas cells with high PTRH2 levels are resistant. In this project, I demonstrated that high PTRH2 expression in Neuroblastoma (NB) patient tumors correlates with poor prognosis, stage 4 metastasis, low mitochondrial Ca2+ and resistance to treatment. NB cells with reduced PTRH2 and PTRH2DF cells display high mitochondrial Ca2+ and enhanced apoptotic response to treatment. In this work, we demonstrate that PTRH2 modulate, by interacting with deubiquitinase Trabid, protein expression of mt-ND5 of mitochondrial complex I. Thus, PTRH2 stabilizes MT-ND5 activity modulating Ca2+ fluxes and ATP levels in mitochondria and protecting cells from stress-induced apoptosis. We propose that PTRH2 is a mitochondrial gatekeeper whereby loss of PTRH2 results in mitochondrial Ca2+ overload and cell death leading to neurodegenerative disease. High PTRH2 expression induces low mitochondrial Ca2+ uptake promoting resistance to cell death and tumor development. Our data provide a mechanistic rationale for the ability of PTRH2 to regulate mitochondrial-induced apoptosis and provide a new starting point for future investigations aimed at identifying new therapies for and against mitochondrial-mediated cell death
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
Calcium signaling from sarcoplasmic reticulum and mitochondria contact sites in acute myocardial infarction
No full text: Acute myocardial infarction (AMI) is a serious condition that occurs when part of the heart is subjected to ischemia episodes, following partial or complete occlusion of the epicardial coronary arteries. The resulting damage to heart muscle cells have a significant impact on patient's health and quality of life. About that, recent research focused on the role of the sarcoplasmic reticulum (SR) and mitochondria in the physiopathology of AMI. Moreover, SR and mitochondria get in touch each other through multiple membrane contact sites giving rise to the subcellular region called mitochondria-associated membranes (MAMs). MAMs are essential for, but not limited to, bioenergetics and cell fate. Disruption of the architecture of these regions occurs during AMI although it is still unclear the cause-consequence connection and a complete overview of the pathological changes; for sure this concurs to further damage to heart muscle. The calcium ion (Ca2+) plays a pivotal role in the pathophysiology of AMI and its dynamic signaling between the SR and mitochondria holds significant importance. In this review, we tried to summarize and update the knowledge about the roles of these organelles in AMI from a Ca2+ signaling point of view. Accordingly, we also reported some possible cardioprotective targets which are directly or indirectly related at limiting the dysfunctions caused by the deregulation of the Ca2+ signaling
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
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Comprehensive Analysis of Mitochondrial Dynamics Alterations in Heart Diseases
Get PDFThe most common alterations affecting mitochondria, and associated with cardiac pathological conditions, implicate a long list of defects. They include impairments of the mitochondrial electron transport chain activity, which is a crucial element for energy formation, and that determines the depletion of ATP generation and supply to metabolic switches, enhanced ROS generation, inflammation, as well as the dysregulation of the intracellular calcium homeostasis. All these signatures significantly concur in the impairment of cardiac electrical characteristics, loss of myocyte contractility and cardiomyocyte damage found in cardiac diseases. Mitochondrial dynamics, one of the quality control mechanisms at the basis of mitochondrial fitness, also result in being dysregulated, but the use of this knowledge for translational and therapeutic purposes is still in its infancy. In this review we tried to understand why this is, by summarizing methods, current opinions and molecular details underlying mitochondrial dynamics in cardiac diseases
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
- …
