SmSP2: A serine protease secreted by the blood fluke pathogen Schistosoma mansoni with anti-hemostatic properties.

BackgroundSerine proteases are important virulence factors for many pathogens. Recently, we discovered a group of trypsin-like serine proteases with domain organization unique to flatworm parasites and containing a thrombospondin type 1 repeat (TSR-1). These proteases are recognized as antigens during host infection and may prove useful as anthelminthic vaccines, however their molecular characteristics are under-studied. Here, we characterize the structural and proteolytic attributes of serine protease 2 (SmSP2) from Schistosoma mansoni, one of the major species responsible for the tropical infectious disease, schistosomiasis.Methodology/principal findingsSmSP2 comprises three domains: a histidine stretch, TSR-1 and a serine protease domain. The cleavage specificity of recombinant SmSP2 was determined using positional scanning and multiplex combinatorial libraries and the determinants of specificity were identified with 3D homology models, demonstrating a trypsin-like endopeptidase mode of action. SmSP2 displayed restricted proteolysis on protein substrates. It activated tissue plasminogen activator and plasminogen as key components of the fibrinolytic system, and released the vasoregulatory peptide, kinin, from kininogen. SmSP2 was detected in the surface tegument, esophageal glands and reproductive organs of the adult parasite by immunofluorescence microscopy, and in the excretory/secretory products by immunoblotting.Conclusions/significanceThe data suggest that SmSP2 is secreted, functions at the host-parasite interface and contributes to the survival of the parasite by manipulating host vasodilatation and fibrinolysis. SmSP2 may be, therefore, a potential target for anti-schistosomal therapy

Synthesis, structure, and opto-electronic properties of organic-based nanoscale heterojunctions

Enormous research effort has been put into optimizing organic-based opto-electronic systems for efficient generation of free charge carriers. This optimization is mainly due to typically high dissociation energy (0.1-1 eV) and short diffusion length (10 nm) of excitons in organic materials. Inherently, interplay of microscopic structural, chemical, and opto-electronic properties plays crucial role. We show that employing and combining advanced scanning probe techniques can provide us significant insight into the correlation of these properties. By adjusting parameters of contact- and tapping-mode atomic force microscopy (AFM), we perform morphologic and mechanical characterizations (nanoshaving) of organic layers, measure their electrical conductivity by current-sensing AFM, and deduce work functions and surface photovoltage (SPV) effects by Kelvin force microscopy using high spatial resolution. These data are further correlated with local material composition detected using micro-Raman spectroscopy and with other electronic transport data. We demonstrate benefits of this multi-dimensional characterizations on (i) bulk heterojunction of fully organic composite films, indicating differences in blend quality and component segregation leading to local shunts of photovoltaic cell, and (ii) thin-film heterojunction of polypyrrole (PPy) electropolymerized on hydrogen-terminated diamond, indicating covalent bonding and transfer of charge carriers from PPy to diamond

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

Determination of Cardinal Directions and the Gesture of OrantDoločitev strani neba in drža oranta

The paper is devoted to an interesting question closely related to the orientations of graves and archaeoastronomical objects in Central Europe, namely, to the determination of cardinal directions during the period ranging from Hallstatt era to Early Middle Ages. Using exhaustive procedure, we have shown that the most likely method for the determination of cardinal directions was that based on the horizontal observation of Sun sets and rises. The intrinsic part of this method is the angle–halving which can be performed either with or without instruments. Reconstruction of the later possibility, supported also by the experimental verification, led us to the conclusion that the hypothetical attitude used for the angle–halving is to be practically identical with the so called gesture of orant, usually interpreted as a posture of early Christian prayer. Interpreting then the burial orientation as a charitable gift, we further claim that the gesture of orant, being originally used for orientation in the unknown terrain, might develop quite naturally into a ritual gesture. Cultural, historical and technical arguments in favour to this idea are given

Astronomische Grundlagen einiger frühmittelalterlichen Kultstellen in PrahaAstronomske osnove nekaterih zgodnjesrednjeveških kultnih točk v Pragi

The authors present a structure of cult points in Prague which was used during the Early Middle Ages. The structure was composed on the basis of astronomical and ritual principles. The former present a sun calendar. The latter principles led the authors to determine the use of a ritual angle, ritual measuring units and their multiples. The entire structure is thus also an ideogram, which supposedly also aided in sustaining equilibrium among the natural forces

Ab initio paramagnetic NMR shifts via point-dipole approximation in a large magnetic-anisotropy Co(II) complex

Abstract Transition metal complexes can possess a large magnetic susceptibility anisotropy, facilitating applications such as paramagnetic tags or shift agents in nuclear magnetic resonance (NMR) spectroscopy. Due to its g-shift and zero-field splitting (ZFS) we demonstrate on a Co(II) clathrochelate with an aliphatic 16-carbon chain, a modern approach for ab initio calculation of paramagnetic susceptibility. Due to its large anisotropy, large linear dimension but relatively low number of atoms, the chosen complex is especially well-suited for testing the long-range point-dipole approximation (PDA) for the pseudocontact shifts (PCSs) of paramagnetic NMR. A static structure of the complex is used to compare the limiting long-distance PDA with full first-principles quantum-mechanical calculation. A non-symmetric formula for the magnetic susceptibility tensor is necessary to be consistent with the latter. Comparison with experimental shifts is performed by conformational averaging over the chain dynamics using Monte Carlo simulation. We observe satisfactory accuracy from the rudimentary simulation and, more importantly, demonstrate the fast applicability of the ab initio PDA

Possible role of extracellular tissue in biological neural networks

In the present paper, we analyze the role of extracellular tissue (ECT) in signal transfer and information processing in biological neural networks. Our speculative approach, which is based mainly on the facts taken from the literature, is completed by simple original models and quantitative estimates. It is shown that the presence of ECT controls some fundamental parameters of immersed biological neural network, which are traditionally treated as intrinsic to neuron membranes. We then propose that the diffusive transfer of action potential via the nervous fiber together with processes induced in the surrounding ECT, is ultimately controlled, in contrast to the standard paradigm, by the quantum diffusion of $$\hbox {Na}^{{+}}$$ and $$\hbox {K}^{{+}}$$ ions, which minimizes the heat production in nervous tissue. Furthermore the diffusion of polarization wave along the axon membrane excites in surrounding ECT temporal potential distribution, which can bias the synapses and dendrites of all vicinal neurons. We claim that just this, so-called, ephaptic coupling between neighboring neurons, completes the local neural network and in fact is responsible for information processing there. Such an idea is obviously incompatible with current models of neural networks of McCulloch–Pitts’ and Rosenblatt’s type, which assume that the information processing takes place exclusively within the neuron soma, being thus convenient merely for the description of artificial neural networks

Diffusive propagation of nervous signals and their quantum control

The governing theory of electric signal transfer through nerve fibre, as established by Hodgkin and Huxley in the 1950s, uses for the description of action potential a clever combination of various concepts of electrochemistry and circuit theory; however, this theory neglects some fundamental features of charge transport through any conductor, e.g., the existence of a temporary charged layer on its boundary accompanied by an external electric field. The consequences of this fact are, among others, the introduction of a non-adequate concept of “conduction velocity” and the obscure idea of saltatory propagation of action potential in myelinaed nerve fibres. Our approach, based on standard transport theory and, particularly, on the submarine cable model, describes the movement of the front of the action potential as a diffusion process characterized by the diffusion constant DE. This process is physically realized by the redistribution of ions in the nervous fluid (axoplasm), which is controlled by another diffusion constant DΩ ≪ DE. Since the action bound with the movement of Na+ and K+ cations prevailing in the axoplasm is comparable with the Planck constant ℏ (i.e. DΩ → ℏ∕2M, where M is ion mass), signal transfer is actually a quantum process. This fact accounts for the astonishing universality of the transfer of action potential, which is proper to quite different species of animals. As is further shown, the observed diversity in the behaviour of nerve tissues is controlled by the scaling factor \sqrt{(D_{\UpOmega} / D_E)}, where DΩ is of a quantum nature and DE of an essentially geometric one