Extracellular Matrix Stiffness and Composition Regulate the Myofibroblast Differentiation of Vaginal Fibroblasts

Fibroblast to myofibroblast differentiation is a key feature of wound-healing in soft tissues, including the vagina. Vaginal fibroblasts maintain the integrity of the vaginal wall tissues, essential to keep pelvic organs in place and avoid pelvic organ prolapse (POP). The micro-environment of vaginal tissues in POP patients is stiffer and has different extracellular matrix (ECM) composition than healthy vaginal tissues. In this study, we employed a series of matrices with known stiffnesses, as well as vaginal ECMs, in combination with vaginal fibroblasts from POP and healthy tissues to investigate how matrix stiffness and composition regulate myofibroblast differentiation in vaginal fibroblasts. Stiffness was positively correlated to production of α-smooth muscle actin (α-SMA). Vaginal ECMs induced myofibroblast differentiation as both α-SMA and collagen gene expressions were increased. This differentiation was more pronounced in cells seeded on POP-ECMs that were stiffer than those derived from healthy tissues and had higher collagen and elastin protein content. We showed that stiffness and ECM content regulate vaginal myofibroblast differentiation. We provide preliminary evidence that vaginal fibroblasts might recognize POP-ECMs as scar tissues that need to be remodeled. This is fundamentally important for tissue repair, and provides a rational basis for POP disease modelling and therapeutic innovations in vaginal reconstruction

Almost global decentralised formation tracking for multiple distinct UAVs

We consider formation control of multiple UAVs, not necessarily identical, by means of a decentralized state feedback controller. The attitude dynamics is formulated on SO(3) to avoid singularities of Euler angles and ambiguity of quaternions, thus allowing for large angular maneuvers, e.g., loopings). Since we explicitly take into account the constraint of non-zero total thrust in our controller design, the controller achieves uniform almost global asymptotic stability instead of only a local result. The trade off between individual trajectory tracking and formation forming is illustrated by means of simulations

Effect of Exogenous Auxin on Root Morphology and Secondary Metabolism in Tagetes-Patula Hairy Root Cultures

Contains fulltext : 29780___.PDF (publisher's version ) (Open Access

Translate the Cradle to Cradle Principles for a Building

Abstract Various guidelines for Cradle to Cradle in the built environment were established since 1992. However, it's not clear how the Cradle to Cradle principles can be translated to the realization of a building. This paper contains information from literature with a focus on applying the Cradle to Cradle principles in building design and -construction. Also results of interviews with experts and directly involved stakeholders, about applying the Cradle to Cradle principles in the built environment will be provided. Specifically a number of aspects and desired results will be addressed, which seem to be essential in the realization of a building

Sequencing of glycosaminoglycans with potential to interrogate sequence-specific interactions

Technologies to sequence nucleic acids/proteins are widely available, but straightforward methodologies to sequence complex polysaccharides are lacking. We here put forward a strategy to sequence glycosaminoglycans, long linear polysaccharides involved in many biochemical processes. The method is based on the covalent immobilization and (immuno)chemical characterization of only those size-separated saccharides that harbor the original reducing end of the full-length chain. Using this methodology, the saccharide sequence of the chondroitin sulfate chain of the proteoglycan bikunin was determined. The method can be performed in any standard biochemical lab and opens studies to the interaction of complex saccharide sequences with other biomolecules

Heparan Sulfate Phage Display Antibodies Identify Distinct Epitopes with Complex Binding Characteristics: INSIGHTS INTO PROTEIN BINDING SPECIFICITIES*

Heparan sulfate (HS) binds and modulates the transport and activity of a large repertoire of regulatory proteins. The HS phage display antibodies are powerful tools for the analysis of native HS structure in situ; however, their epitopes are not well defined. Analysis of the binding specificities of a set of HS antibodies by competitive binding assays with well defined chemically modified heparins demonstrates that O-sulfates are essential for binding; however, increasing sulfation does not necessarily correlate with increased antibody reactivity. IC50 values for competition with double modified heparins were not predictable from IC50 values with corresponding singly modified heparins. Binding assays and immunohistochemistry revealed that individual antibodies recognize distinct epitopes and that these are not single linear sequences but families of structurally similar motifs in which subtle variations in sulfation and conformation modify the affinity of interaction. Modeling of the antibodies demonstrates that they possess highly basic CDR3 and surrounding surfaces, presenting a number of possible orientations for HS binding. Unexpectedly, there are significant differences between the existence of epitopes in tissue sections and observed in vitro in dot blotted tissue extracts, demonstrating that in vitro specificity does not necessarily correlate with specificity in situ/vivo. The epitopes are therefore more complex than previously considered. Overall, these data have significance for structure-activity relationships of HS, because the model of one antibody recognizing multiple HS structures and the influence of other in situ HS-binding proteins on epitope availability are likely to reflect the selectivity of many HS-protein interactions in vivo