Two-phase stretching of molecular chains

While stretching of most polymer chains leads to rather featureless force-extension diagrams, some, notably DNA, exhibit non-trivial behavior with a distinct plateau region. Here we propose a unified theory that connects force-extension characteristics of the polymer chain with the convexity properties of the extension energy profile of its individual monomer subunits. Namely, if the effective monomer deformation energy as a function of its extension has a non-convex (concave up) region, the stretched polymer chain separates into two phases: the weakly and strongly stretched monomers. Simplified planar and 3D polymer models are used to illustrate the basic principles of the proposed model. Specifically, we show rigorously that when the secondary structure of a polymer is mostly due to weak non-covalent interactions, the stretching is two-phase, and the force-stretching diagram has the characteristic plateau. We then use realistic coarse-grained models to confirm the main findings and make direct connection to the microscopic structure of the monomers. We demostrate in detail how the two-phase scenario is realized in the \alpha-helix, and in DNA double helix. The predicted plateau parameters are consistent with single molecules experiments. Detailed analysis of DNA stretching demonstrates that breaking of Watson-Crick bonds is not necessary for the existence of the plateau, although some of the bonds do break as the double-helix extends at room temperature. The main strengths of the proposed theory are its generality and direct microscopic connection.Comment: 16 pges, 22 figure

Apoptosis induced by the Tibetan herbal remedy PADMA 28 in the T cell-derived lymphocytic leukaemia cell line CEM-C7H2

The Tibetan herbal remedy PADMA 28 revealed promising results to support treatment of atherosclerosis, Charot syndrome (intermittent claudication), chronic active hepatitis and infection of the respiratory tract. The remedy was confirmed to be closely linked with anti- and pro-oxidative properties in vitro. In this study, apoptogenic and survival effects of PADMA 28 were investigated in the T cell-derived lymphocytic leukaemia cell line CEM-C7H2. PADMA 28 led to a concentration-dependent inhibition of cell proliferation accompanied by the accumulation of CEM-C7H2 cells in subG1 phase, fragmentation of poly (ADP-ribose) polymerase (PARP) and nuclear body formation. Treatment with PADMA 28 rescued to some extent cells over-expressing Bcl-2 from apoptosis. This finding suggests that the mechanism of action of PADMA 28 may be via interference with Bcl-2 triggered survival pathways

3D‐Printed Inherently Porous Structures with Tetrahedral Lattice Architecture: Experimental and Computational Study of Their Mechanical Behavior

Increasing demand in automotive, construction, and medical industries for materials with reduced weight and high mechanical durability has given rise to porous materials and composites. Materials combining nano- and microporosity and a well-defined cellular macroporous architecture offer great potential weight reduction while maintaining mechanical durability. To achieve predictable mechanical performance, it is essential to apply experimental and computational efforts to precisely describe material structure–properties relationships. This study explores polymer structures with polymerization-inherited porosity and well-defined macroporous geometry, fabricated via digital light processing (DLP) 3Dprinting. Pore size and relative density are varied by ink composition and printing parameters to track their influence on the structure stiffness. Simulated stiffness values for the base polymer correspond to the experimentally determined elastic properties, showing Young\u27s moduli of 554–722 MPa depending on the cosolvent ratio, which confirms the structure–properties relationship. Macroporosity is introduced in the form of a 3D tetrahedral bending-dominated architecture with the resulting specific Young\u27s moduli of 79.5 MPa cm$^3$ g$^{−1}$ , comparable to foams. To merge the gap in stiffnesses, further investigation of structure–property relationships of various 3D–printed lattice architectures, as well as its application to other stereolithography methods to eliminate the negative effects from printing artifacts and resolution limit of the DLP 3D-printing, are envisioned

Identification of regeneration-associated genes after central and peripheral nerve injury in the adult rat

Background: It is well known that neurons of the peripheral nervous system have the capacity to regenerate a severed axon leading to functional recovery, whereas neurons of the central nervous system do not regenerate successfully after injury. The underlying molecular programs initiated by axotomized peripheral and central nervous system neurons are not yet fully understood.Results: To gain insight into the molecular mechanisms underlying the process of regeneration in the nervous system, differential display polymerase chain reaction has been used to identify differentially expressed genes following axotomy of peripheral and central nerve fibers. For this purpose, axotomy induced changes of regenerating facial nucleus neurons, and non-regenerating red nucleus and Clarke's nucleus neurons have been analyzed in an intra-animal side-to-side comparison. One hundred and thirty five gene fragments have been isolated, of which 69 correspond to known genes encoding for a number of different functional classes of proteins such as transcription factors, signaling molecules, homeobox-genes, receptors and proteins involved in metabolism. Sixty gene fragments correspond to genomic mouse sequences without known function. In situ-hybridization has been used to confirm differential expression and to analyze the cellular localization of these gene fragments. Twenty one genes (similar to 15%) have been demonstrated to be differentially expressed.Conclusions: The detailed analysis of differentially expressed genes in different lesion paradigms provides new insights into the molecular mechanisms underlying the process of regeneration and may lead to the identification of genes which play key roles in functional repair of central nervous tissues

Allelopathic studies with furanocoumarins isolated from Ducrosia anethifolia. vitro and in silico investigations to protect legumes, rice and grain crops

Six different furanocoumarins were isolated from the aerial parts of Ducrosia anethifolia and tested in vitro for plant cell elongation in etiolated wheat coleoptile. They were also tested for their ability to control three different weeds: ribwort plantain, annual ryegrass, and common purslane. These compounds exhibited strong inhibition of plant cell elongation. In the case of (+)-heraclenin, the IC50 was lower than 20 mu M, indicating a better inhibition than the positive control Logran (R). Computational experiments for docking and molecular dynamics revealed for the investigated furanocoumarins bearing an epoxide moiety an improved fitting and stronger interaction with the auxin-like TIR1 ubiquitin ligase. Furthermore, the formed inhibition complex remained also stable during dynamic evaluation. Bidental interaction at the active site, along with an extended hydrogen-bond lifetime, explained the enhanced activity of the epoxides. The in vitro weed bioassay results showed that Plantago lan-ceolata was the most affected weed for germination, root, and shoot development. In addition, (+)-heraclenin displayed better inhibition values than positive control even at 300 mu M concentration

Precursor proteins in transit through mitochondrial contact sites interact with hsp70 in the matrix

We previously reported that hsp70 in the mitochondrial matrix (mt-hsp70 = Ssc1p) is required for import of precursor proteins destined for the matrix or intermembrane space. Here we show that mt-hsp70 is also needed for the import of mitochondrial inner membrane proteins. In particular, the precursor of ADP/ATP carrier that is known not to interact with hsp60 on its assembly pathway requires functional mt-hsp70 for import, suggesting a general role of mt-hsp70 in membrane translocation of precursors. Moreover, a precursor arrested in contact sites was specifically co-precipitated with antibodies directed against mt-hsp70. We conclude that mt-hsp70 is directly involved in the translocation of many, if not all, precursor proteins that are transported across the inner membrane

Integrated diagnostics: proceedings from the 9th biennial symposium of the International Society for Strategic Studies in Radiology

The International Society for Strategic Studies in Radiology held its 9th biennial meeting in August 2011. The focus of the programme was integrated diagnostics and massive computing. Participants discussed the opportunities, challenges, and consequences for the discipline of radiology that will likely arise from the integration of diagnostic technologies. Diagnostic technologies are increasing in scope, including advanced imaging techniques, new molecular imaging agents, and sophisticated point-of-use devices. Advanced information technology (IT), which is increasingly influencing the practice of medicine, will aid clinical communication and the development of “population images” that represent the phenotype of particular diseases, which will aid the development of diagnostic algorithms. Integrated diagnostics offer increased operational efficiency and benefits to patients through quicker and more accurate diagnoses. As physicians with the most expertise in IT, radiologists are well placed to take the lead in introducing IT solutions and cloud computing to promote integrated diagnostics. To achieve this, radiologists must adapt to include quantitative data on biomarkers in their reports. Radiologists must also increase their role as participating physicians, collaborating with other medical specialties, not only to avoid being sidelined by other specialties but also to better prepare as leaders in the selection and sequence of diagnostic procedures