1,720,960 research outputs found
Caratterizzazione della via BMP in cachessia tumorale
No full textLa cachessia tumorale è una sindrome metabolica multifattoriale caratterizzata da un’eccessiva perdita di peso dovuta a un progressivo catabolismo di massa magra e massa grassa che rappresenta più della metà dei pazienti oncologici. La perdita di massa muscolare e di forza sono considerate tra i caratteri clinici più rilevanti in cachessia associata a cancro e un fattore prognostico negativo per il paziente.
Il pathway Bone Morphogenetic Protein (BMP)-Smad1/5/8 è un pathway regolatorio positivo per il mantenimento della massa muscolare. Abbiamo dimostrato che i ridotti livelli di SMAD1/5/8, un indicatore dell’attività via BMP, assumono un ruolo critico per l’insorgenza della cachessia tumorale e che la riattivazione della via BMP nel muscolo è sufficiente ad attenuare l’atrofia muscolare indotta dal tumore, dimostrando che un intervento BMP specifico nel muscolo può avere delle potenziali terapeutiche.
Siccome la via BMP dipende dai fattori di trascrizione SMAD1/5/8 e da numerosi ligandi, recettori e inibitori il cui trascritto viene modulato nel muscolo, abbiamo ipotizzato che la presenza del tumore influisca sul trascrittoma del muscolo, portando ad un’inibizione della via BMP in risposta alla crescita tumorale e di conseguenza all’insorgenza del fenotipo cachettico.
Abbiamo proceduto con un approccio unbiased e genome-wide per investigare il rimodellamento della cromatina che potrebbe avvenire in cachessia associata a cancro. Abbiamo eseguito un esperimento di ChIP-seq per H3K27Ac, un marker istonico di attività trascrizionale, nei muscoli di topi con tumore C26 e in topi sani. Nei muscoli di topi con tumore C26 è emerso un aumento di istoni acetilati (ovvero che rappresentano una cromatina aperta, trascrizionalmente attiva), rispetto al gruppo di controllo. L’analisi bioinformatica ha identificato le vie BMP e TGF-β tra le 20 vie con maggiore iperacetilazione istonica più rappresentative in cachessia. Abbiamo cercato potenziali siti di legami di fattori di trascrizione che sono trascrizionalmente modulati in condizioni di cachessia tumorale.
Per avere una visione collettiva di come l’eterogeneità delle cellule muscolari rispondono alla cachessia associata a cancro nel muscolo e per capire quali sono i tipi cellulari che contribuiscono a inibire la via BMP,
abbiamo condotto un esperimento di single nucleus Multiome ATAC and Gene Expression su tibiali anteriori di topi sani e topi con tumore C26. Questo approccio produce una misura simultanea all’interno del singolo nucleo dell’espressione dell’RNA (snRNA-seq) e dell’accessibilità della cromatina (snATAC-seq).
Abbiamo esaminato per ogni singola popolazione cellulare il livello di espressione di alcune componenti della via BMP, per valutare come la loro espressione cambia in risposta alla cachessia.
Al di là dell’espressione del singolo gene, abbiamo interrogato il nostro dataset di sn multiomic in maniera unbiased e abbiamo ottenuto informazioni circa le pathway che sono interessate in ogni popolazione cellulare in condizioni di cachessia tumorale.
Dal momento che un approccio multiomico può fornire informazioni riguardo allo stato della cromatina aperta delle diverse popolazioni cellulari, nelle future analisi monitoreremo i geni che sono differenzialmente upregolati nei muscoli cachettici e presentano stati di cromatina aperta nelle regioni promotoriali. L’obiettivo finale di questa ricerca è quello di studiare queste specifiche regioni promotoriali aperte per identificare, attraverso metodi bioinformatici, i siti di legami di fattori di trascrizione per capire quali potenziali vie del segnale sono coinvolte nei cambiamenti trascrizionali che portano al fenotipo cachettico nelle diverse sottopopolazioni cellulari, con il fine di investigare nuovi rilevanti meccanismi molecolari con potenziale terapeutico.Cancer cachexia is a multi-factorial metabolic syndrome characterized by excessive body weight loss due to progressive fat and lean mass catabolism occurring in more than half of cancer patients. The loss of skeletal muscle mass and strength are considered as the most relevant features of cancer cachexia and predictors of poor outcomes.
Bone Morphogenetic Protein (BMP)/Smad1/5/8 pathway is a positive regulator of muscle mass homeostasis. We demonstrated that diminished Smad1/5/8 signalling in muscles plays a critical role for the onset of cancer cachexia and that reactivation of the BMP pathway in the muscles of tumor-bearing mice prevents muscle wasting. The transcriptional activity of Smad1/5/8 is specifically required to mediate a beneficial effect on muscle mass. Moreover, several components of the BMP pathway are transcriptionally modulated in cachectic muscles.
Using an unbiased genome-wide approach to investigate the chromatin remodeling that may occur in cancer cachexia, we performed ChIP-seq experiments in muscles to characterize histone modifications.
We focused on H3K27Ac, a histone mark of active regulatory elements. An increase of acetylated histones was detected in muscles of C26-tumor bearing mice, compared to the control group. Process enrichment analysis reported the BMP pathway among the top 20 pathways with hyperacetylated histones. We searched for potential transcription factors binding sites in the hyperacetylated promoters of different BMP pathway components that are transcriptionally modulated in the context of cancer cachexia.
To gather a comprehensive view on how the heterogeneity of muscle cells respond to cancer cachexia in skeletal muscle and on which are the cell types contributing to BMP dysregulation, we performed a single nucleus Multiome ATAC and Gene Expression experiment on tibialis anterior of control and C26 tumor-bearing mice. This approach provides simultaneous measurement within each individual nucleus of RNA expression (snRNA-seq) and chromatin accessibility (snATAC-seq).
We investigated at the level of the single cell population the expression level of some BMP components, to evaluate how their expression change in response to cachexia.
Beyond the single gene expression, we interrogated the sn multiomic data in an unbiased way and retrieve information about the most affected pathways in each cell population in the cachectic condition.
Since multiomic approach can provide information on the open chromatin status of the different cell populations, in the future we will check for genes that are differentially upregulated in cachectic muscles and show an open chromatin in their promoter regions. The final aim is to study these regions to bioinformatically identify transcription factors binding sites to understand which putative signaling pathways are responsible for the transcriptional changes that lead to the cachectic phenotype in the different cell subpopulations in order to exploit new relevant molecular mechanisms with therapeutic potential.
Our aim is to understand how cancer stimulates transcriptional changes leading to BMP-Smad1/5/8 inhibition in skeletal muscles to favor cachexia onset in order to identify new potential therapeutic targets
Cutaneous blastic plasmacytoid dendritic cell neoplasm: Successful palliative treatment with oral prednisone in an elderly patient
No full text
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
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
- …
