The Assembling and Contraction Mechanisms of Striated Muscles

A novel approach to the description of the assembly mechanism of functional biological structures is presented. The approach is based on the identification of fundamental self-assembling processes to which an additional structurization “engineered” by Nature to optimize functions is superimposed. Application of the approach to the structure and contraction of the striated muscle evidences a key role of the residual liquid crystallinity of a constrained structure and the alteration of the compatibility between the thin and thick filaments driven by ionic interactions. ATP hydrolysis boosts the relaxation process. A strong protein scaffold, engineered during the evolutionary process and based on the selective anchoring of coordinated filaments, directs a demixing tendency of the two filaments toward a sliding motion along the fiber axis. The Huxley-Hanson sliding filament hypothesis aimed to explain the contraction-relaxation function of the striated muscle, but does not offer any clue on the overall assembling mechanism of the myofibril

Adalimumab efficacy in enteropathic spondyloarthritis: A 12-mo observational multidisciplinary study

AIM To report adalimumab (Ada) efficacy on articulargastrointestinal disease and health-related quality of life (HRQoL) in patients with enteropathic spondyloarthritis (ES). METHODS A cohort of 52 patients with ES was evaluated in the departments of gastroenterology and internal medicine. At baseline, all patients underwent assessment by an integrated gastro-rheumatologic evaluation of articular and gastrointestinal activity, as well patient reported outcomes (PROs) of the HRQoL questionnaires. After this integrated evaluation and following a specific working flowchart, the Ada anti-tumor necrosis factor (TNF)-inhibitor was assigned to a cohort of 30 patients and its clinical efficacy was evaluated at baseline and after 6-mo and 12-mo treatment by the following tests: (1) Ankylosing Spondylitis Disease Activity Score- C-Reactive Protein (ASDAS-CRP); Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI) for articular activity; (2) Inflammatory Bowel Disease Questionnaire (IBDQ), Crohn's Disease Activity Index (CDAI) and partial Mayo (pMayo) score for gastrointestinal symptoms and activity; and (3) Health Assessment Questionnaire (HAQ), Patient Global Assessment (PGA) and Short Form-36 health survey (SF-36) questionnaires for PROs of the HRQoL. RESULTS Integrated evaluation and management of the patients affected by ES, carried out simultaneously by a gastroenterologist and a rheumatologist, allowed clinicians to choose the optimal therapeutic strategy. In a cohort of 30 ES patients affected by active articular and gastrointestinal disease, or axial active articular inflammation, Ada led to fast and sustained improvement of both articular and gastrointestinal disease activities. In fact, all the clinimetric evaluation tests exploring articular or gastrointestinal activity, as well as all the HRQoL scores, showed a significant improvement having been achieved at the earliest (6-mo) assessment. This important clinical improvement was maintained at the 12-mo follow-up. Importantly, global and gastrointestinal quality of life significantly correlated with articular disease activity, providing evidence to support that the integrated evaluation is the best option to manage patients with ES. CONCLUSION Ada treatment, upon multidisciplinary (gastrorheumatologic) evaluation, significantly improves both articular and gastrointestinal inflammation, thereby improving the HRQoL in patients affected by ES

Random, blocky and alternating ordering in supramolecular polymers of chemically bidisperse monomers

As a first step to understanding the role of molecular or chemical polydispersity in self-assembly, we put forward a coarse-grained model that describes the spontaneous formation of quasi-linear polymers in solutions containing two self-assembling species. Our theoretical framework is based on a two-component self-assembled Ising model in which the bidispersity is parameterized in terms of the strengths of the binding free energies that depend on the monomer species involved in the pairing interaction. Depending upon the relative values of the binding free energies involved, different morphologies of assemblies that include both components are formed, exhibiting paramagnetic-, ferromagnetic- or anti ferromagnetic-like order,i.e., random, blocky or alternating ordering of the two components in the assemblies. Analyzing the model for the case of ferromagnetic ordering, which is of most practical interest, we find that the transition from conditions of minimal assembly to those characterized by strong polymerization can be described by a critical concentration that depends on the concentration ratio of the two species. Interestingly, the distribution of monomers in the assemblies is different from that in the original distribution, i.e., the ratio of the concentrations of the two components put into the system. The monomers with a smaller binding free energy are more abundant in short assemblies and monomers with a larger binding affinity are more abundant in longer assemblies. Under certain conditions the two components congregate into separate supramolecular polymeric species and in that sense phase separate. We find strong deviations from the expected growth law for supramolecular polymers even for modest amounts of a second component, provided it is chemically sufficiently distinct from the main one.Comment: Submitted to Macromolecules, 6 figures. arXiv admin note: substantial text overlap with arXiv:1111.176

Shear-Modulus Investigations of Monohydroxy Alcohols: Evidence for a Short-Chain-Polymer Rheological Response

In addition to the ubiquitous structural relaxation of viscous supercooled liquids, monohydroxy alcohols and several other hydrogen-bonded systems display a strong single-exponential electrical low-frequency absorption. So far, this so-called Debye process could be observed only using dielectric techniques. Exploiting a combination of broad-band and high-resolution rheology experiments for three isomeric octanols, unambiguous mechanical evidence for the Debye process is found. Its spectral signature is similar to the viscoelastic fingerprint of small-chain polymers, enabling us to estimate the effective molecular weight for the supramolecular structure formed by the studied monohydroxy alcohols. This finding opens the venue for the application of further non-dielectric techniques directed at unraveling the microscopic nature of the Debye process and for an understanding of this phenomenon in terms of polymer concepts.Comment: 12 pages, 4 figure

Self-assembly in solution of a reversible comb-shaped supramolecular polymer

We report a single step synthesis of a polyisobutene with a bis-urea moiety in the middle of the chain. In low polarity solvents, this polymer self-assembles by hydrogen bonding to form a combshaped polymer with a central hydrogen bonded backbone and polyisobutene arms. The comb backbone can be reversibly broken, and consequently, its length can be tuned by changing the solvent, the concentration or the temperature. Moreover, we have proved that the bulkiness of the side-chains have a strong influence on both the self-assembly pattern and the length of the backbone. Finally, the density of arms can be reduced, by simply mixing with a low molar mass bis-urea

Compaction of Rods: Relaxation and Ordering in Vibrated, Anisotropic Granular Material

We report on experiments to measure the temporal and spatial evolution of packing arrangements of anisotropic, cylindrical granular material, using high-resolution capacitive monitoring. In these experiments, the particle configurations start from an initially disordered, low-packing-fraction state and under vertical vibrations evolve to a dense, highly ordered, nematic state in which the long particle axes align with the vertical tube walls. We find that the orientational ordering process is reflected in a characteristic, steep rise in the local packing fraction. At any given height inside the packing, the ordering is initiated at the container walls and proceeds inward. We explore the evolution of the local as well as the height-averaged packing fraction as a function of vibration parameters and compare our results to relaxation experiments conducted on spherically shaped granular materials.Comment: 9 pages incl. 7 figure

Structural basis for HCMV Pentamer receptor recognition and antibody neutralization

Human cytomegalovirus (HCMV) represents the viral leading cause of congenital birth defects and uses the gH/ gL/UL128-130-131A complex (Pentamer) to enter different cell types, including epithelial and endothelial cells. Upon infection, Pentamer elicits the most potent neutralizing response against HCMV, representing a key vaccine candidate. Despite its relevance, the structural basis for Pentamer receptor recognition and antibody neutralization is largely unknown. Here, we determine the structures of Pentamer bound to neuropilin 2 (NRP2) and a set of potent neutralizing antibodies against HCMV. Moreover, we identify thrombomodulin (THBD) as a functional HCMV receptor and determine the structures of the Pentamer-THBD complex. Unexpectedly, both NRP2 and THBD also promote dimerization of Pentamer. Our results provide a framework for understanding HCMV receptor engagement, cell entry, antibody neutralization, and outline strategies for antiviral therapies against HCMV

Evaluation of a gelatin-based adhesive for historic paintings that incorporates citronella oil as an eco-friendly biocide

[EN] The presented study focuses on evaluating the efficiency of a gelatin-based product that incorporates a plasticizer (glycerol) and a biocide (citronella oil), proposed as an eco-friendly adhesive for polychrome decoration applied in different parts of the architectural complex of the Longshan Temple in Lukang (eighteenth century, Taiwan). Seven laboratory physico-chemical tests were performed: (a) viscosity measurement; (b) drying curves; (c) moisture content determination; (d) water vapor permeability test; (e) mechanical test; (f) adhesion test; (g) susceptibility to fungi colonization test, which provide information on the workability, water content and water barrier properties, as well as mechanical, adhesion, and the biocide properties of the proposed product. The obtained results indicate that the workability, mechanical and adhesive properties of the new adhesive are adequate. Permeability in polychromies is slightly reduced due to the additional barrier effect of the adhesive incorporated into the paint film. The efficiency of citronella oil for preventing the growth of fungus Aspergillus niger on paintings consolidated with the adhesive was also probed. In parallel to these laboratory trials, the micro-invasive tests carried out, using nanoindentation combined with atomic force microscopy (NI-AFM), provided direct evidence for the improvement in the mechanical properties induced by applying the new adhesive to the original polychromies.This work was supported by the Spanish Ministerio de Economia, Industria y Competitividad (MINECO), the Fondo Europeo de Desarrollo Regional (ERDF), and the Agencia Estatal de Investigacion (AEI).Lee, Y.; Martín Rey, S.; Osete Cortina, L.; Martín-Sánchez, I.; Domenech Carbo, MT.; Bolivar-Galiano, F. (2018). Evaluation of a gelatin-based adhesive for historic paintings that incorporates citronella oil as an eco-friendly biocide. Journal of Adhesion Science and Technology. 32(21):2320-2349. https://doi.org/10.1080/01694243.2018.1477411S23202349322

Kebab: Kinetochore and EB1 Associated Basic Protein That Dynamically Changes Its Localisation during Drosophila Mitosis

Microtubule plus ends are dynamic ends that interact with other cellular structures. Microtubule plus end tracking proteins are considered to play important roles in the regulation of microtubule plus ends. Recent studies revealed that EB1 is the central regulator for microtubule plus end tracking proteins by recruiting them to microtubule plus ends through direct interaction. Here we report the identification of a novel Drosophila protein, which we call Kebab (kinetochore and EB1 associated basic protein), through in vitro expression screening for EB1-interacting proteins. Kebab fused to GFP shows a novel pattern of dynamic localisation in mitosis. It localises to kinetochores weakly in metaphase and accumulates progressively during anaphase. In telophase, it associates with microtubules in central-spindle and centrosomal regions. The localisation to kinetochores depends on microtubules. The protein has a domain most similar to the atypical CH domain of Ndc80, and a coiled-coil domain. The interaction with EB1 is mediated by two SxIP motifs but is not required for the localisation. Depletion of Kebab in cultured cells by RNA interference did not show obvious defects in mitotic progression or microtubule organisation. Generation of mutants lacking the kebab gene indicated that Kebab is dispensable for viability and fertility

Aurora B potentiates Mps1 activation to ensure rapid checkpoint establishment at the onset of mitosis

The mitotic checkpoint prevents mitotic exit until all chromosomes are attached to spindle microtubules. Aurora B kinase indirectly invokes this checkpoint by destabilizing incorrect attachments; however, a more direct role remains controversial. In contrast, activity of the kinase Mps1 is indispensible for the mitotic checkpoint. Here we show that Aurora B and Hec1 are needed for efficient Mps1 recruitment to unattached kinetochores, allowing rapid Mps1 activation at the onset of mitosis. Live monitoring of cyclin B degradation reveals that this is essential to establish the mitotic checkpoint quickly at the start of mitosis. Delayed Mps1 activation and checkpoint establishment upon Aurora B inhibition or Hec1 depletion are rescued by tethering Mps1 to kinetochores, demonstrating that Mps1 recruitment is the primary role of Aurora B and Hec1 in mitotic checkpoint signalling. These data demonstrate a direct role for Aurora B in initiating the mitotic checkpoint rapidly at the onset of mitosis