The actin crosslinking protein palladin modulates force generation and mechanosensitivity of tumor associated fibroblasts

Cells organize actin filaments into higher-order structures by regulating the composition, distribution and concentration of actin crosslinkers. Palladin is an actin crosslinker found in the lamellar actin network and stress fibers, which are critical for mechanosensing of the environment. Palladin also serves as a molecular scaffold for α-actinin, another key actin crosslinker. By virtue of its close interactions with actomyosin structures in the cell, palladin may play an important role in cell mechanics. However, the role of palladin in cellular force generation and mechanosensing has not been studied. Here, we investigate the role of palladin in regulating the plasticity of the actin cytoskeleton and cellular force generation in response to alterations in substrate stiffness. Traction force microscopy revealed that tumor-associated fibroblasts generate larger forces on substrates of increased stiffness. Contrary to expectations, knocking down palladin increased the forces generated by cells and inhibited their ability to sense substrate stiffness for very stiff gels. This was accompanied by significant differences in actin organization, adhesion dynamics and altered myosin organization in palladin knock-down cells. Our results suggest that actin crosslinkers such as palladin and myosin motors coordinate for optimal cell function and to prevent aberrant behavior as in cancer metastasis

Thermal rectification effects of multiple semiconductor quantum dot junctions

Based on the multiple energy level Anderson model, this study theoretically examines the thermoelectric effects of semiconductor quantum dots (QDs) in the nonlinear response regime. The charge and heat currents in the sequential tunneling process are calculated by using the Keldysh Green's function technique. Results show that the thermal rectification effect can be observed in a multiple QD junction system, whereas the tunneling rate, size fluctuation, and location distribution of QD significantly influence the rectification efficiency.Comment: 5 pages, 8figure

Exact microscopic theory of electromagnetic heat transfer between a dielectric sphere and plate

Near-field electromagnetic heat transfer holds great potential for the advancement of nanotechnology. Whereas far-field electromagnetic heat transfer is constrained by Planck's blackbody limit, the increased density of states in the near-field enhances heat transfer rates by orders of magnitude relative to the conventional limit. Such enhancement opens new possibilities in numerous applications, including thermal-photo-voltaics, nano-patterning, and imaging. The advancement in this area, however, has been hampered by the lack of rigorous theoretical treatment, especially for geometries that are of direct experimental relevance. Here we introduce an efficient computational strategy, and present the first rigorous calculation of electromagnetic heat transfer in a sphere-plate geometry, the only geometry where transfer rate beyond blackbody limit has been quantitatively probed at room temperature. Our approach results in a definitive picture unifying various approximations previously used to treat this problem, and provides new physical insights for designing experiments aiming to explore enhanced thermal transfer.Comment: 1 page title 8 page content 1 page references 2 page figure captions 4 page figure

The role of palladin in actin organization and cell motility

Palladin is a widely expressed protein found in stress fibers, focal adhesions, growth cones, Z-discs, and other actin-based subcellular structures. It belongs to a small gene family that includes the Z-disc proteins myopalladin and myotilin, all of which share similar Ig-like domains. Recent advances have shown that palladin shares with myotilin the ability to bind directly to F-actin, and to crosslink actin filaments into bundles, in vitro. Studies in a variety of cultured cells suggest that the actin-organizing activity of palladin plays a central role in promoting cell motility. Correlative evidence also supports this hypothesis, as palladin levels are typically upregulated in cells that are actively migrating: in developing vertebrate embryos, in cells along a wound edge, and in metastatic cancer cells. Recently, a mutation in the human palladin gene was implicated in an unusually penetrant form of inherited pancreatic cancer, which has stimulated new ideas about the role of palladin in invasive cancer

An interaction between alpha-actinin and the beta 1 integrin subunit in vitro

A number of cytoskeletal-associated proteins that are concentrated in focal contacts, namely alpha-actinin, vinculin, talin, and integrin, have been shown to interact in vitro such that they suggest a potential link between actin filaments and the membrane. Because some of these interactions are of low affinity, we suspect the additional linkages also exist. Therefore, we have used a synthetic peptide corresponding to the cytoplasmic domain of beta 1 integrin and affinity chromatography to identify additional integrin-binding proteins. Here we report our finding of an interaction between the cytoplasmic domain of beta 1 integrin and the actin-binding protein alpha-actinin. Beta 1- integrin cytoplasmic domain peptide columns bound several proteins from Triton extracts of chicken embryo fibroblasts. One protein at approximately 100 kD was identified by immunoblot analysis as alpha- actinin. Solid phase binding assays indicated that alpha-actinin bound specifically and directly to the beta 1 peptide with relatively high affinity. Using purified heterodimeric chicken smooth muscle integrin (a beta 1 integrin) or the platelet integrin glycoprotein IIb/IIIa complex (a beta 3 integrin), binding of alpha-actinin was also observed in similar solid phase assays, albeit with a lower affinity than was seen using the beta 1 peptide. alpha-Actinin also bound specifically to phospholipid vesicles into which glycoprotein IIb/IIIa had been incorporated. These results lead us to suggest that this integrin-alpha- actinin linkage may contribute to the attachment of actin filaments to the membrane in certain locations

In-Network Outlier Detection in Wireless Sensor Networks

To address the problem of unsupervised outlier detection in wireless sensor networks, we develop an approach that (1) is flexible with respect to the outlier definition, (2) computes the result in-network to reduce both bandwidth and energy usage,(3) only uses single hop communication thus permitting very simple node failure detection and message reliability assurance mechanisms (e.g., carrier-sense), and (4) seamlessly accommodates dynamic updates to data. We examine performance using simulation with real sensor data streams. Our results demonstrate that our approach is accurate and imposes a reasonable communication load and level of power consumption.Comment: Extended version of a paper appearing in the Int'l Conference on Distributed Computing Systems 200

Cytoplasmic Ig-domain proteins: Cytoskeletal regulators with a role in human disease

Immunoglobulin domains are found in a wide variety of functionally diverse transmembrane proteins, and also in a smaller number of cytoplasmic proteins. Members of this latter group are usually associated with the actin cytoskeleton, and most of them bind directly to either actin or myosin, or both. Recently, studies of inherited human disorders have identified disease-causing mutations in five cytoplasmic Ig-domain proteins: myosin-binding protein C, titin, myotilin, palladin, and myopalladin. Together with results obtained from cultured cells and mouse models, these clinical studies have yielded novel insights into the unexpected roles of Ig domain proteins in mechanotransduction and signaling to the nucleus. An emerging theme in this field is that cytoskeleton-associated Ig domain proteins are more than structural elements of the cell, and may have evolved to fill different needs in different cellular compartments

Designing libraries of chimeric proteins using SCHEMA recombination and RASPP

SCHEMA is a method for designing libraries of novel proteins by recombination of homologous sequences. The goal is to maximize the number of folded proteins while simultaneously generating significant sequence diversity. Here, we use the RASPP algorithm to identify optimal SCHEMA designs for shuffling contiguous elements of sequence. To exemplify the method, SCHEMA is used to recombine five fungal cellobiohydrolases (CBH1s) to produce a library of more than 390,000 novel CBH1 sequences

Are we training our novices towards quality 2D profiles for 3D models?

In the history-based, feature-based, parametric CAD approach, 2D profile sketches are the basis for 3D models. Fully-constraining profiles is mandatory to create robust profiles. At present, neither CAD applications nor Model Quality Testing Tools usually check whether 2D profiles contain redundant constraints. Besides, our experience shows that novices tend to introduce redundant constraints. We hypothesize that 2D profiles over-constrained with redundant relations are more difficult to edit than those that avoid redundancies. In the present work―and as a first step to demonstrate this hypothesis―an experiment was conducted. Students of the subject “Graphics engineering” were taught on the creation of constrained 2D profiles. Then, they were asked two questions. On the one hand, novices had to identify and reason whether a simple given profile was fully-constrained, over-constrained or under-constrained. On the other hand, they had to identify and point out the types of the constraints. The results showed that in spite that novices received a specific training, roughly half of them failed to say if the 2D profile sketch was fully-constrained and which type of constraints it contained. Furthermore, the results of the second question revealed that more than the half of students did not recognize perpendicularity as a geometric constraint. As future work, we will try to demonstrate whether a reinforced training through simple exercises and a quick and effective feedback, will allow novices to improve the identification and removal of redundant 2D constraints when drawing 2D profile sketches (thus helping to produce robust profiles)