Nano-building block based-hybrid organic–inorganic copolymers with self-healing properties

New dynamic materials, that can repair themselves after strong damage, have been designed by hybridization of polymers with structurally well-defined nanobuilding units. The controlled design of cross-linked poly(n-butyl acrylate) (pBuA) has been performed by introducing a very low amount of a specific tin oxo-cluster. Sacrificial domains with non-covalent interactions (i.e. ionic bonds) developed at the hybrid interface play a double role. Such interactions are strong enough to cross-link the polymer, which consequently exhibits rubber-like elasticity behavior and labile enough to enable, after severe mechanical damage, dynamic bond recombination leading to an efficient healing process at room temperature. In agreement with the nature of the reversible links at the hybrid interface, the healing process can speed up considerably with temperature. 1H and 119Sn PFG NMR has been used to evidence the dynamic nature of these peculiar cross-linking nodes

Reversible Cortical Blindness Following Successful Surgical Repair Of Two Stab Wounds In The Heart

This report describes a case of cortical blindness that followed successful surgical repair of two stab wounds in the heart in a 29-year old Libyan man. The patient presented in a state of pre cardiac arrest (shock and low cardiac output status), following multiple chest stab wounds. Chest tube was immediately inserted. Surgery was urgently performed suturing the two wounds; in the root of the aorta and in the left ventricle, and haemostasis was secured. Cardiac arrest was successfully prevented. The patient recovered smoothly, but 24 hours later he declared total blindness. Ophtalmic and neurological examinations and investigations that included fundoscopy, Electroencephalograms (EEGs) and Computed Tomography Scans revealed no abnormalities, apart from absence of alpha waves in the EEGs. We diagnosed the case as cortical blindness and continued caring for the patient conservatively. Three days later, the patient regained his vision gradually and was discharged on the 7th postoperative day without any remarks

How the central domain of dystrophin acts to bridge F-actin to sarcolemmal lipids

Dystrophin is a large intracellular protein that prevents sarcolemmal ruptures by providing a mechanical link between the intracellular actin cytoskeleton and the transmembrane dystroglycan complex. Dystrophin deficiency leads to the severe muscle wasting disease Duchenne Muscular Dystrophy and the milder allelic variant, Becker Muscular Dystrophy (DMD and BMD). Previous work has shown that concomitant interaction of the actin binding domain 2 (ABD2) comprising spectrin like repeats 11 to 15 (R11-15) of the central domain of dystrophin, with both actin and membrane lipids, can greatly increase membrane stiffness. Based on a combination of SAXS and SANS measurements, mass spectrometry analysis of cross-linked complexes and interactive low-resolution simulations, we explored in vitro the molecular properties of dystrophin that allow the formation of ABD2-F-actin and ABD2-membrane model complexes. In dystrophin we identified two subdomains interacting with F-actin, one located in R11 and a neighbouring region in R12 and another one in R15, while a single lipid binding domain was identified at the C-terminal end of R12. Relative orientations of the dystrophin central domain with F-actin and a membrane model were obtained from docking simulation under experimental constraints. SAXS-based models were then built for an extended central subdomain from R4 to R19, including ABD2. Overall results are compatible with a potential F-actin/dystrophin/membrane lipids ternary complex. Our description of this selected part of the dystrophin associated complex bridging muscle cell membrane and cytoskeleton opens the way to a better understanding of how cell muscle scaffolding is maintained through this essential protein

10 simple rules to create a serious game, illustrated with examples from structural biology

Serious scientific games are games whose purpose is not only fun. In the field of science, the serious goals include crucial activities for scientists: outreach, teaching and research. The number of serious games is increasing rapidly, in particular citizen science games, games that allow people to produce and/or analyze scientific data. Interestingly, it is possible to build a set of rules providing a guideline to create or improve serious games. We present arguments gathered from our own experience ( Phylo , DocMolecules , HiRE-RNA contest and Pangu) as well as examples from the growing literature on scientific serious games

Preservation of micro-architecture and angiogenic potential in a pulmonary acellular matrix obtained using intermittent intra-tracheal flow of detergent enzymatic treatment

Tissue engineering of autologous lung tissue aims to become a therapeutic alternative to transplantation. Efforts published so far in creating scaffolds have used harsh decellularization techniques that damage the extracellular matrix (ECM), deplete its components and take up to 5 weeks to perform. The aim of this study was to create a lung natural acellular scaffold using a method that will reduce the time of production and better preserve scaffold architecture and ECM components. Decellularization of rat lungs via the intratracheal route removed most of the nuclear material when compared to the other entry points. An intermittent inflation approach that mimics lung respiration yielded an acellular scaffold in a shorter time with an improved preservation of pulmonary micro-architecture. Electron microscopy demonstrated the maintenance of an intact alveolar network, with no evidence of collapse or tearing. Pulsatile dye injection via the vasculature indicated an intact capillary network in the scaffold. Morphometry analysis demonstrated a significant increase in alveolar fractional volume, with alveolar size analysis confirming that alveolar dimensions were maintained. Biomechanical testing of the scaffolds indicated an increase in resistance and elastance when compared to fresh lungs. Staining and quantification for ECM components showed a presence of collagen, elastin, GAG and laminin. The intratracheal intermittent decellularization methodology could be translated to sheep lungs, demonstrating a preservation of ECM components, alveolar and vascular architecture. Decellularization treatment and methodology preserves lung architecture and ECM whilst reducing the production time to 3 h. Cell seeding and in vivo experiments are necessary to proceed towards clinical translation

Col V siRNA Engineered Tenocytes for Tendon Tissue Engineering

The presence of uniformly small collagen fibrils in tendon repair is believed to play a major role in suboptimal tendon healing. Collagen V is significantly elevated in healing tendons and plays an important role in fibrillogenesis. The objective of this study was to investigate the effect of a particular chain of collagen V on the fibrillogenesis of Sprague-Dawley rat tenocytes, as well as the efficacy of Col V siRNA engineered tenocytes for tendon tissue engineering. RNA interference gene therapy and a scaffold free tissue engineered tendon model were employed. The results showed that scaffold free tissue engineered tendon had tissue-specific tendon structure. Down regulation of collagen V α1 or α2 chains by siRNAs (Col5α1 siRNA, Col5α2 siRNA) had different effects on collagen I and decorin gene expressions. Col5α1 siRNA treated tenocytes had smaller collagen fibrils with abnormal morphology; while those Col5α2 siRNA treated tenocytes had the same morphology as normal tenocytes. Furthermore, it was found that tendons formed by coculture of Col5α1 siRNA treated tenocytes with normal tenocytes at a proper ratio had larger collagen fibrils and relative normal contour. Conclusively, it was demonstrated that Col V siRNA engineered tenocytes improved tendon tissue regeneration. And an optimal level of collagen V is vital in regulating collagen fibrillogenesis. This may provide a basis for future development of novel cellular- and molecular biology-based therapeutics for tendon diseases

The Necrotic Signal Induced by Mycophenolic Acid Overcomes Apoptosis-Resistance in Tumor Cells

The amount of inosine monophosphate dehydrogenase (IMPDH), a pivotal enzyme for the biosynthesis of the guanosine tri-phosphate (GTP), is frequently increased in tumor cells. The anti-viral agent ribavirin and the immunosuppressant mycophenolic acid (MPA) are potent inhibitors of IMPDH. We recently showed that IMPDH inhibition led to a necrotic signal requiring the activation of Cdc42.Herein, we strengthened the essential role played by this small GTPase in the necrotic signal by silencing Cdc42 and by the ectopic expression of a constitutive active mutant of Cdc42. Since resistance to apoptosis is an essential step for the tumorigenesis process, we next examined the effect of the MPA–mediated necrotic signal on different tumor cells demonstrating various mechanisms of resistance to apoptosis (Bcl2-, HSP70-, Lyn-, BCR-ABL–overexpressing cells). All tested cells remained sensitive to MPA–mediated necrotic signal. Furthermore, inhibition of IMPDH activity in Chronic Lymphocytic Leukemia cells was significantly more efficient at eliminating malignant cells than apoptotic inducers.These findings indicate that necrosis and apoptosis are split signals that share few if any common hub of signaling. In addition, the necrotic signaling pathway induced by depletion of the cellular amount of GTP/GDP would be of great interest to eliminate apoptotic-resistant tumor cells

Study on Composition Distribution and Ferromagnetism of Monodisperse FePt Nanoparticles

Monodisperse FePt nanoparticles with size of 4.5 and 6.0 nm were prepared by simultaneous reduction of platinum acetylacetonate and thermal decomposition of iron pentacarbonyl in benzylether. The crystallography structure, size, and composition of the FePt nanoparticles were examined by X-ray diffraction and transmission electron microscopy. Energy dispersive X-ray spectrometry measurements of individual particles indicate a broad compositional distribution in both the 4.5 and 6 nm FePt nanoparticles. The effects of compositional distribution on the phase-transition and magnetic properties of the FePt nanoparticles were investigated