1,720,959 research outputs found
Theranostic impact of NG2/CSPG4 proteoglycan in cancer
No full textNG2/CSPG4 is an unusual cell-membrane integral proteoglycan widely recognized to be a prognostic factor, a valuable tool for ex vivo and non-invasive molecular diagnostics and, by virtue of its tight association with malignancy, a tantalizing therapeutic target in several tumour types. Although the biology behind its involvement in cancer progression needs to be better understood, implementation of NG2/CSPG4 in the routine clinical practice is attainable and has the potential to contribute to an improved individualized management of cancer patients. In this context, its polymorphic nature seems to be particularly valuable in the effort to standardize informative diagnostic procedures and consolidate forcible immunotherapeutic treatment strategies. We discuss here the underpinnings for this potential and highlight the benefits of taking advantage of the intra- tumour and inter-patient variability in the regulation of NG2/CSPG4 expression. We envision that NG2/CSPG4 may effectively be exploited in therapeutic interventions aimed at averting resistance to target therapy agents and at interfering with secondary lesion formation and/or tumour recurrence
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
STRUCTURAL AND FUNCTIONAL TRAITS OF NG2/CSPG4 PROTEOGLYCAN IN RELATION TO ITS ROLE IN TUMORS
No full textChondroitin Sulphate Proteoglycan-4 (NG2/CSPG4) is a transmembrane proteoglycan consisting of a N-linked glycoprotein of 280 kDa and a proteoglycan component of about 450 kDa. It is expressed on the surface of various types of immature progenitor cells and its expression decreases with terminal differentiation. NG2/CSPG4 is expressed in several human malignant tumors playing an important role in growth, migration, and metastatic dissemination of tumor cells and it is involved in promotion of tumor progression. Aberrant expression of NG2/CSPG4 on cancer cells and angiogenic vasculature is observed in association with an aggressive disease course in several malignancies. Moreover, NG2/CSPG4 is expressed on the surface of both tumor cells and pericytes, and its distribution in normal tissue can be considered relatively restricted, so to be considered an attractive candidate for simultaneously targeting the malignant and stromal cellular compartments within the tumour. NG2/CSPG4 can trigger rearrangements of the actin cytoskeleton and interacts with components of the extracellular matrix, playing a role in both growth control and motility of cells.
The singularity of NG2/CSPG4 structure suggests that it might also be unique in terms of its ability to participate in inter- and intra-molecular interactions. As a membrane-spanning molecule, NG2/CSPG4 has the potential to interact with its cytoplasmic domain, the large extracellular portion, and the glycosaminoglycan chain it carries on the core protein to participate in signaling between the extracellular and intracellular compartments of the cell, guiding the activation of important survival and growth pathways in tumors. Because of its structure, distribution and functions, NG2/CSPG4 has been proposed to promote tumor progression by multiple mechanisms and may represent a putative target for molecular therapy against cancer.
To obtain anti-NG2/CSPG4 monoclonal antibodies (mAbs) we performed a systematical production of mAbs with the hybridoma technology, where immunization has been performed employing the extracellular portion of recombinant NG2/CSPG4 protein and from this immunization 63 clones have been selected and they have been characterized. We employed these mAbs to establish the expression patterns and subcellular distribution of NG2/CSPG4 in tumor cells and tissues, and to investigate the existence of NG2/CSPG4 isoforms among different tumors. The reactivity of mAbs against NG2/CSPG4 expressed from different cells or tissues, let us hypothesize that diverse isoforms of NG2/CSPG4 are expressed among the different tumors.
As NG2 may represents a putative target for cancer molecular therapy against cancer, we employed our panel of anti-NG2/CPSG4 mAbs as a useful instrument to study in vitro their effect, with the aim to select those able to interfere with the functions that NG2 plays in tumors cells growth, survival, adhesion, migration.
NG2 seems to interact with many molecules with its cytoplasmic domain, the large extracellular portion, and the glycosaminoglycan chain it carries on the core protein. In this contests, the last part of this research focus on the study of NG2/CSPG4’s putative interactors, carried on through a proteomic approach with mass spectrometry on tumor cell lines. MALDI-TOF analysis let us confirm some of the interactors already demonstrated in literature, and interestingly we identified some important putative interactors never found before, involved in cell migration. This finding open new ways to our research in target therapy against tumors.NG2/CSPG4 è un proteoglicano transmembrana costituito da una glicoproteina di 280 kDa e da una componente proteoglicanica di circa 450 kDa. E’ espresso sulla superficie di vari tipi di cellule progenitrici immature e la sua espressione diminuisce durante il differenziamento. E’ espresso in diversi tumori maligni nei quali svolge un ruolo centrale nella crescita, migrazione e diffusione metastatica del tumore e sembra favorire la progressione tumorale. L’espressione di NG2/CSPG4 risulta modulata nelle cellule tumorali e sui vasi angiogenici, e tale regolazione è spesso associata a un decorso aggressivo in vari tumori maligni. E’ diffuso sulla superficie sia delle cellule tumorali che dei periciti, e la sua distribuzione nel tessuto sano può essere considerata relativamente limitata, in modo da deputare NG2/CSPG4 come un candidato ideale per il targeting sia dei compartimenti cellulari maligni che stromali all'interno del tumore. NG2/CSPG4 in quanto transmembrana, può sia innescare riarrangiamenti citoscheletrici con il suo dominio citoplasmatico, che interagire con i componenti della matrice extracellulare mediante il dominio extracellulare, investendo un ruolo fondamentale sia nel controllo della crescita che della motilità delle cellule. Inoltre questo proteoglicano sfrutta per le sue interazioni anche la catena di condroitin solfato, di cui è fornito il core proteico, per reclutare interattori extracellulari o di membrana. Queste interazioni sembrano conferire ad NG2/CSPG4 un ruolo centrale nelle vie di segnalazione tra i compartimenti extra- ed intra-cellulari, guidando la sopravvivenza e la crescita delle cellule tumorali in cui risulta essere espresso. Per tanto, grazie alle sue peculiari caratteristiche di struttura, distribuzione, e le funzione, NG2/CSPG4 sembra essere un probabile promotore della progressione tumorale ponendosi quindi come bersaglio ottimale nella terapia molecolare contro il cancro.
In tale contesto, per ottenere anticorpi monoclonali (mAbs) anti-NG2/CSPG4 abbiamo avviato nel nostro laboratorio una produzione sistematica di mAbs da ibridomi, ottenuti impiegando il dominio extracellulare della proteina come immunogeno. Da questa immunizzazione sono stati selezionati e caratterizzati 63 cloni e loro subcloni. Abbiamo utilizzato questi anticorpi monoclonali per studiare i pattern di espressione di diverse linee cellulari tumorali e la distribuzione subcellulare di NG2/CSPG4 in questi tipi di tumori, al fine di indagare l’esistenza di diverse isoforme NG2/CSPG4 espresse nei vari tipi di tumori. La variabilità con cui tali mAbs riconoscono il loro antigene, tra le diverse linee cellulari testate, fa ipotizzare che diversi tumori esprimono diverse isoforme di NG2/CSPG4. Siccome NG2/CSPG4 è stato proposto come putativo bersaglio per un’eventuale terapia molecolare traghettata contro melanoma, sarcoma, mesoltelioma e carcinoma mammario, abbiamo sfruttato il nostro pannello di anticorpi anti-NG2/CPSG4 per studiare le loro funzionalità in vitro con lo scopo di selezionare quelli in grado di interferire con le principali funzioni di NG2 nella crescita, sopravvivenza, adesione, e migrazione cellulare.
Dato che NG2/CSPG4, con i suoi domini, sembra interagire con diverse molecole, una parte di questa ricerca è stata dedicata allo studio di tali eventuali interattori, che abbiamo condotto con un approccio proteomico mediante spettrometria di massa. Dai risultati ottenuti dalle analisi MALDI-TOF non solo abbiamo confermato alcuni degli interattori di NG2/CSPG4 già noti in letteratura, bensì abbiamo individuato nuovi interattori putativi, i quali risultano per lo più a loro volta coinvolti nei processi di migrazione cellulare e nell’organizzazione del citoscheletro.
Questi risultati aprono la strada ad indagini più mirate, con lo scopo di caratterizzare la natura delle isoforme di NG2/CSPG4 e le loro diverse funzioni, e di approfondire le interazioni che tali molecole hanno in un contesto tumorale
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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe 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
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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