1,720,976 research outputs found

    Superposition of Substrate Deformation Fields Induced by Molecular Clutches Explains Cell Spatial Sensing of Ligands

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    Cells can sense the physical properties of the extracellular matrices (ECMs), such as stiffness and ligand density, through cell adhesions to actively regulate their behaviors. Recent studies have shown that varying ligand spacing of ECMs can influence adhesion size, cell spreading, and even stem cell differentiation, indicating that cells have the spatial sensing ability of ECM ligands. However, the mechanism of the cells' spatial sensing remains unclear. In this study, we have developed a lattice-spring motor-clutch model by integrating cell membrane deformation, the talin unfolding mechanism, and the lattice spring for substrate ligand distribution to explore how the spatial distribution of integrin ligands and substrate stiffness influence cell spreading and adhesion dynamics. By applying the Gillespie algorithm, we found that large ligand spacing reduces the superposition effect of the substrate's displacement fields generated by pulling force from motor-clutch units, increasing the effective stiffness probed by the force-sensitive receptors; this finding explains a series of previous experiments. Furthermore, using the mean-field theory, we obtain the effective stiffness sensed by bound clutches analytically; our analysis shows that the bound clutch number and ligand spacing are the two key factors that affect the superposition effects of deformation fields and, hence, the effective stiffness. Overall, our study reveals the mechanism of cells' spatial sensing, i.e., ligand spacing changes the effective stiffness sensed by cells due to the superposition effect of deformation fields, which provides a physical clue for designing and developing biological materials that effectively control cell behavior and function

    A chemo-mechanical model for growth and mechanosensing of focal adhesion

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    Focal adhesion (FA), the complex molecular assembly across the lipid membrane, serves as a hub for physical and chemical information exchange between cells and their microenvironment. Interestingly, studies have shown that FAs can grow along the direction of contractile forces generated by actomyosin stress fibers and achieve larger sizes on stiffer substrates. In addition, the cellular traction transmitted to the substrate was observed to reach the maximum near the FA center. However, the biomechanical mechanisms behind these intriguing findings remain unclear. To answer this important question, here we first developed a one-dimensional (1D) chemo-mechanical model of FA where key features like adhesion plaque deformation, active contraction by stress fibers, force-dependent association/dissociation of integrin bonds connecting two surfaces, and substrate compliance have all been considered. Within this formulation, we showed that the rigidity-sensing capability of FAs originates from the deformability of stress fibers while the force-dependent breakage of integrin bonds leads to the appearance of the traction peak at the FA center. Furthermore, by extending the model into three-dimensional as well as incorporating assembly/dis-assembly kinetics of adhesion proteins, we also demonstrated how anisotropic stress/strain field within the adhesion plaque will be induced by the presence of contractile forces which leads to the directional growth of the FA

    Ca2+ transmembrane transport enhances oscillatory growth of cancer cell invadopodia

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    Abstract Invadopodia, dynamic cancer cell protrusions, deform and degrade extracellular matrix (ECM) to facilitate invasion. Intracellular calcium ions (Ca2+) are critical second messengers involved in cancer cells migration, proliferation, and apoptosis, but their role in invadopodia dynamics remains unclear. Here, we propose a chemo-mechanical model integrating Ca2+ transmembrane transport, myosin contractility, adhesion dynamics, actin polymerization, and membrane type 1 matrix metalloproteinase (MT1-MMP) hydrolysis. We find that increased invadopodia length elevates membrane tension, activating mechanosensitive channels and raising intracellular Ca2+ levels, aligning with experimental observations. Our model reveals that invadopodia oscillatory and monotonic dynamics are governed by actin polymerization and myosin recruitment, with Ca2+ transport enhancing dynamics via myosin recruitment and reciprocal effects on Ca2+ transport. Furthermore, by incorporating MT1-MMP-mediated ECM degradation in our model, we find that ECM degradation promotes invadopodia extension and elevates Ca2+ levels, which shifts the invadopodia dynamics from monotonic to oscillatory. Overall, our model offers a comprehensive theoretical framework for understanding Ca2+ transport and invadopodia dynamics in cancer cells

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    “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

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    We 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

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    We 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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We 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
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