Bone morphogenetic protein 2 improves patellar tendon healing by promoting migration and proliferation of tenocytes

The repair of injured tendons remains a great challenge because of the poor intrinsic healing capacity of tendons. In this study, we examined the spatiotemporal expression pattern of the bone morphogenetic protein 2 (bmp-2) gene in normal and experimentally injured rat patellar tendons. We also investigated the ability of exogenously applied BMP-2 to promote patellar tendon healing. In situ hybridization with bmp-2 and alk-6 (bmp-2 receptor) antisense riboprobes revealed that both genes were normally expressed at low levels in intact rat tendons. However, bmp-2 expression was significantly upregulated in tenocytes found in the wound site at 7 d and later following tendon injury. In addition, it was found that bmp-2 was expressed in cultured patellar tenocytes. Appli- cation of exogenous BMP-2 to the tendon wound site significantly enhanced tendon repair. Moreover, in vitro and in vivo studies further demonstrated that BMP-2 enhanced tenocyte proliferation and migration to the wound site. The detectable amount of BMP-2 in normal tendons suggests that a basal level of bmp-2 expression was likely present to maintain the normal functions of the patellar tendon. Injury to the tendon induced increased bmp-2 expression intrinsically, but the expression level was insufficient for proper tendon repair. Our findings indicate that it is possible to significantly improve tendon healing by applying exogenous BMP-2 to the wound site, inferring that this protein could be developed as a potential therapeutic reagent for the treatment of damaged tendons.     

Elevational patterns and determinants of plant diversity in the Baekdudaegan Mountains, South Korea: Species vs. functional diversity

The elevational gradient present in mountainous areas provides the most powerful natural experimental system available to clarify the ecological and evolutionary responses of living organisms to geophysical influences. In this study, we explored the elevational patterns of plant species and functional diversity and the effects of area, mid-domain effect, climatic variables and net primary productivity on the observed diversity patterns along the ridge of the Baekdudaegan Mountains, South Korea. Rapoport’s elevational rule was also evaluated by examining the relationship between elevational range size of plant species and elevation. A total of 802 plant species from 97 families and 342 genera were found in 1100 plots along a 200–-1900-m elevational gradient along the ridge. The elevational patterns of plant species diversity along the ridge of the Baekdudaegan depicted distinctly hump-shaped patterns, whereas the functional diversity decreased monotonically with elevation. The mid-domain effect was the most powerful explanatory variable for species diversity patterns. However, climatic variables were better predictors for functional diversity. Moreover, Rapoport’s elevational rule was not supported. Our study suggests that different elevational patterns may be observed among different diversity measurements even in the same taxon and that there may be fundamental differences in the mechanisms underlying these diversity patterns.     

Synthesis of Au–Ag alloy nanoparticles supported on silica gel via galvanic replacement reaction

Synthesis of supported Au-Ag bimetallic has attracted much attention since we found for the first time that Au and Ag had synergistic effect on CO oxidation and preferential CO oxidation in rich hydrogen.In this work,the formation of Au-Ag alloy nanoparticles supported on silica gel by galvanic replacement reaction has been investigated.We applied various characterizations including X-ray diffraction(XRD),transmission electronic microscopy(TEM),ultraviolet-visible spectroscopy(UV-vis),X-ray absorption spectroscopy(XAS) to characterize the formation process of Au-Ag alloy.Although the average particle sizes of the Au-Ag alloy nanoparticles obtained by the galvanic replacement reaction are relatively large comparing with that of loading Au first,the catalytic activity of the catalyst in preferential CO oxidation is almost the same.This result manifested that the particle size effect of Au-Ag nanoparticles was not as tremendous as that of monometallic gold.The formation of Au-Ag alloy made it less sensitive to the particle size.     

Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor

Ebola virus (EBOV) entry requires the surface glycoprotein (GP) to initiate attachment and fusion of viral and host membranes. Here we report the crystal structure of EBOV GP in its trimeric, pre-fusion conformation (GP1+GP2) bound to a neutralizing antibody, KZ52, derived from a human survivor of the 1995 Kikwit outbreak. Three GP1 viral attachment subunits assemble to form a chalice, cradled by the GP2 fusion subunits, while a novel glycan cap and projected mucin-like domain restrict access to the conserved receptor-binding site sequestered in the chalice bowl. The glycocalyx surrounding GP is likely central to immune evasion and may explain why survivors have insignificant neutralizing antibody titres. KZ52 recognizes a protein epitope at the chalice base where it clamps several regions of the pre-fusion GP2 to the amino terminus of GP1. This structure provides a template for unravelling the mechanism of EBOV GP-mediated fusion and for future immunotherapeutic development.     

CLEC5A is critical for dengue-virus-induced lethal disease

Dengue haemorrhagic fever and dengue shock syndrome, the most severe responses to dengue virus (DV) infection, are characterized by plasma leakage (due to increased vascular permeability) and low platelet counts. CLEC5A (C-type lectin domain family 5, member A; also known as myeloid DAP12-associating lectin (MDL-1)) contains a C-type lectin-like fold similar to the natural-killer T-cell C-type lectin domains and associates with a 12-kDa DNAX-activating protein (DAP12) on myeloid cells. Here we show that CLEC5A interacts with the dengue virion directly and thereby brings about DAP12 phosphorylation. The CLEC5A-DV interaction does not result in viral entry but stimulates the release of proinflammatory cytokines. Blockade of CLEC5A-DV interaction suppresses the secretion of proinflammatory cytokines without affecting the release of interferon-alpha, supporting the notion that CLEC5A acts as a signalling receptor for proinflammatory cytokine release. Moreover, anti-CLEC5A monoclonal antibodies inhibit DV-induced plasma leakage, as well as subcutaneous and vital-organ haemorrhaging, and reduce the mortality of DV infection by about 50% in STAT1-deficient mice. Our observation that blockade of CLEC5A-mediated signalling attenuates the production of proinflammatory cytokines by macrophages infected with DV (either alone or complexed with an enhancing antibody) offers a promising strategy for alleviating tissue damage and increasing the survival of patients suffering from dengue haemorrhagic fever and dengue shock syndrome, and possibly even other virus-induced inflammatory diseases.     

A paracrine requirement for hedgehog signalling in cancer

Ligand-dependent activation of the hedgehog (Hh) signalling pathway has been associated with tumorigenesis in a number of human tissues. Here we show that, although previous reports have described a cell-autonomous role for Hh signalling in these tumours, Hh ligands fail to activate signalling in tumour epithelial cells. In contrast, our data support ligand-dependent activation of the Hh pathway in the stromal microenvironment. Specific inhibition of Hh signalling using small molecule inhibitors, a neutralizing anti-Hh antibody or genetic deletion of smoothened (Smo) in the mouse stroma results in growth inhibition in xenograft tumour models. Taken together, these studies demonstrate a paracrine requirement for Hh ligand signalling in the tumorigenesis of Hh-expressing cancers and have important implications for the development of Hh pathway antagonists in cancer.     

How Cooper pairs vanish approaching the Mott insulator in Bi2Sr2CaCu2O8+delta

The antiferromagnetic ground state of copper oxide Mott insulators is achieved by localizing an electron at each copper atom in real space (r-space). Removing a small fraction of these electrons (hole doping) transforms this system into a superconducting fluid of delocalized Cooper pairs in momentum space (k-space). During this transformation, two distinctive classes of electronic excitations appear. At high energies, the mysterious 'pseudogap' excitations are found, whereas, at lower energies, Bogoliubov quasi-particles-the excitations resulting from the breaking of Cooper pairs-should exist. To explore this transformation, and to identify the two excitation types, we have imaged the electronic structure of Bi(2)Sr(2)CaCu(2)O(8+delta) in r-space and k-space simultaneously. We find that although the low-energy excitations are indeed Bogoliubov quasi-particles, they occupy only a restricted region of k-space that shrinks rapidly with diminishing hole density. Concomitantly, spectral weight is transferred to higher energy r-space states that lack the characteristics of excitations from delocalized Cooper pairs. Instead, these states break translational and rotational symmetries locally at the atomic scale in an energy-independent way. We demonstrate that these unusual r-space excitations are, in fact, the pseudogap states. Thus, as the Mott insulating state is approached by decreasing the hole density, the delocalized Cooper pairs vanish from k-space, to be replaced by locally translational- and rotational-symmetry-breaking pseudogap states in r-space.     

TMEM16A confers receptor-activated calcium-dependent chloride conductance

Calcium (Ca(2+))-activated chloride channels are fundamental mediators in numerous physiological processes including transepithelial secretion, cardiac and neuronal excitation, sensory transduction, smooth muscle contraction and fertilization. Despite their physiological importance, their molecular identity has remained largely unknown. Here we show that transmembrane protein 16A (TMEM16A, which we also call anoctamin 1 (ANO1)) is a bona fide Ca(2+)-activated chloride channel that is activated by intracellular Ca(2+) and Ca(2+)-mobilizing stimuli. With eight putative transmembrane domains and no apparent similarity to previously characterized channels, ANO1 defines a new family of ionic channels. The biophysical properties as well as the pharmacological profile of ANO1 are in full agreement with native Ca(2+)-activated chloride currents. ANO1 is expressed in various secretory epithelia, the retina and sensory neurons. Furthermore, knockdown of mouse Ano1 markedly reduced native Ca(2+)-activated chloride currents as well as saliva production in mice. We conclude that ANO1 is a candidate Ca(2+)-activated chloride channel that mediates receptor-activated chloride currents in diverse physiological processes.     

A Decision Support Method for Truck Scheduling and Storage Allocation Problem at Container

Truck scheduling and storage allocation, as two separate subproblems in port operations, have been deeply studied in past decades. However, from the operational point of view, they are highly interdependent. Storage allocation for import containers has to balance the travel time and queuing time of each container in yard. This paper proposed an integer programming model handling these two problems as a whole. The objective of this model is to reduce congestion and waiting time of container trucks in the terminal so as to decrease the makespan of discharging containers. Due to the inherent complexity of the prob-lem, a genetic algorithm and a greedy heuristic algorithm are designed to attain near optimal solutions. It shows that the heuristic algorithm can achieve the optimal solution for small-scale problems. The solutions of small-and large-scale problems obtained from the heuristic algorithm are better than those from the genetic algorithm.     

Hot deformation behavior andfl ow stress modeling of annealed AZ61 Mg alloys

In this study, the hyperbolic-sine type constitutive equation was used to model the flow stress of annealed AZ61 magnesium(Mg) alloys. Hot compression tests were conducted at the temperatures ranging from 250 1C to 450 1C and at the strain rates ranging from 1 10–3s 1to 1 s 1on a Gleeble-3500 thermo-simulation machine. Constitutive equations as a function of strain were established through a simple extension of the hyperbolic sine constitutive relation. The effects of annealing heat treatments on the variations in constitutive parameters with strain were discussed. The hot compressive flow curves exhibited typical features of dynamic recrystallization. Multiple peak flow curves were observed in the annealed specimens upon testing at a strain rate of 1 10 1s–1and at various temperatures. Variations in constitutive parameters with strain were related to flow behavior and dependent on the initial conditions of the test specimens. The flow stresses of annealed AZ61 Mg alloys were predicted well by the strain-dependent constitutive equations of the hyperbolic sine function under the deformation conditions employed in this study.