1,720,962 research outputs found
Driving the pancreatic β-cell function through nanoscale features: the influence of nuclear mechanotransduction
No full textBackground and aims: nowadays, to accelerate the development of cell-replacement strategies in diabetes, there is a desperate need to understand mechanisms and stimuli regulating the β-cell development and function. We have recently demonstrated that the extracellular nanotopography promotes β-cell survival, differentiation, and function through the activation of a mechanotransductive pathway, however, the underlying molecular mechanisms need to be further investigated. In the last years, we focused on how mechanical forces might impact the nuclear organization, and thus the transcriptional and translational activities in pancreatic β-cells.
Materials and methods: human isolated islets were cultured for 20 days on nanostructured zirconia substrates with a controllable ECM-like roughness (ns-ZrOx), while flat zirconia substrates were used as controls (flat-ZrO2). The activation of nuclear mechanotransduction was assessed by super-resolution fluorescence microscopy and western blot technique and confirmed by shot-gun proteomic.
Results: we found that the nanotopography, by reducing the cytoskeletal tension, modulates the nuclear shape and architecture (nuclear area and circularity; p<0.001 ns-ZrOx vs flat-ZrO2). These modifications are paralleled by the spatial reorganization of the nuclear lamina, and a shift of lamin isoforms in the islets grown on the nanosubstrates (p<0.05 ns-ZrOx vs flat-ZrO2). Changes in nuclear lamina might affect the access of transcription factors to the nucleus leading to changes in the transcriptional and translational activities. In accordance, the proteomic analysis revealed the upregulation of chromatin-associated proteins (GO:0031497), RNA binding proteins (GO:0003723), spliceosome (GO:0005681) and heterogeneous nuclear ribonucleoprotein (GO:0030529) complexes in the islets grown on the nanostructure (p<0.05 ns-ZrOx vs flat-ZrO2). Furthermore, we observed that the nanostructure modulates the expression of YAP/TAZ, a soluble transcription factor strictly controlled by mechanical forces and critically involved in the regulation of the β-cell fate (p<0.05 ns-ZrOx vs flat-ZrO2).
Conclusions: our data indicate for the first time that the extracellular nanotopography controls the transcriptional and translational activities of pancreatic β-cells, further supporting the hypothesis of a mechanical-induced β-cell reprogramming. These findings provide a better understanding of the mechanotransductive-regulatory mechanisms in β-cells, revealing novel pathways and molecular effectors that may be helpful for designing engineered substrates that can improve the efficacy of replacing therapies in diabetes
Promoting Pancreatic β-cell Differentiation and Function: The Influence of Nanotopography
No full textUnderstanding how to control β-cell differentiation is of paramount importance in diabetes research. Pancreatic β-cells in vivo develop in a peculiar niche and are constantly exposed to chemical and physical cues arising from the surrounding extracellular matrix; while the effects of chemical stimuli have been widely characterized, poorly is known about the mechanical signals.
By exploiting cluster-assembled zirconia substrates with tailored roughness to mimic the ECM nanotopography, we investigated its impact on β-cell fate. We found that the nanotopography preserve β-cell differentiation and function in long-term cultured islets. Proteomic analysis and quantitative immunofluorescence revealed that β-cells sense and respond to the nanotopography activating a mechanotransductive pathway which causes the remodeling of the cell-substrate adhesions, the reorganization of the actin cytoskeleton and the nuclear architecture, thus changing gene expression. We also provide evidence that the nanotopography evokes a mitomorphosis program, favoring mitochondrial networking and function.
In conclusion, our data suggest that β-cells respond to nanoscale features by activating a mechanotransduction pathway which promotes their survival and function. Engineering microenvironment mirroring the biophysical properties of the islet niche may offer a unique strategy to elucidate how mechanical forces contribute to β-cell fate and to harness these mechanisms for promoting β-cell function
Impact of pancreatic PCSK9 on intracellular organelles architecture and dynamics in beta-cells: implication in insulin processing and secretion
No full textGoing Beyond Counting First Authors in Author Co-citation Analysis
No full textThe 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
No full text“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
No full textWe 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
No full textWe 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
Regulating the pancreatic β-cell functionality through nanotopographical cues: focus on organelles organisation and crosstalk
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