Glycosylation of Candida albicans cell wall proteins is critical for induction of innate immune responses and apoptosis of epithelial cells.

C. albicans is one of the most common fungal pathogen of humans, causing local and superficial mucosal infections in immunocompromised individuals. Given that the key structure mediating host-C. albicans interactions is the fungal cell wall, we aimed to identify features of the cell wall inducing epithelial responses and be associated with fungal pathogenesis. We demonstrate here the importance of cell wall protein glycosylation in epithelial immune activation with a predominant role for the highly branched N-glycosylation residues. Moreover, these glycan moieties induce growth arrest and apoptosis of epithelial cells. Using an in vitro model of oral candidosis we demonstrate, that apoptosis induction by C. albicans wild-type occurs in early stage of infection and strongly depends on intact cell wall protein glycosylation. These novel findings demonstrate that glycosylation of the C. albicans cell wall proteins appears essential for modulation of epithelial immunity and apoptosis induction, both of which may promote fungal pathogenesis in vivo

On the nature of symbolic execution

In this paper, we provide a formal definition of symbolic execution in terms of a symbolic transition system and prove its correctness with respect to an operational semantics which models the execution on concrete values. We first introduce such a formal model for a basic programming language with a statically fixed number of programming variables. This model is extended to a programming language with recursive procedures which are called by a call-by-value parameter mechanism. Finally, we show how to extend this latter model of symbolic execution to arrays and object-oriented languages which feature dynamically allocated variables

Self-organized network evolution coupled to extremal dynamics

The interplay between topology and dynamics in complex networks is a fundamental but widely unexplored problem. Here, we study this phenomenon on a prototype model in which the network is shaped by a dynamical variable. We couple the dynamics of the Bak-Sneppen evolution model with the rules of the so-called fitness network model for establishing the topology of a network; each vertex is assigned a fitness, and the vertex with minimum fitness and its neighbours are updated in each iteration. At the same time, the links between the updated vertices and all other vertices are drawn anew with a fitness-dependent connection probability. We show analytically and numerically that the system self-organizes to a non-trivial state that differs from what is obtained when the two processes are decoupled. A power-law decay of dynamical and topological quantities above a threshold emerges spontaneously, as well as a feedback between different dynamical regimes and the underlying correlation and percolation properties of the network.Comment: Accepted version. Supplementary information at http://www.nature.com/nphys/journal/v3/n11/suppinfo/nphys729_S1.htm

Randomized trial of Legflow® paclitaxel eluting balloon and stenting versus standard percutaneous transluminal angioplasty and stenting for the treatment of intermediate and long lesions of the superficial femoral artery (RAPID trial): Study protocol for a randomized controlled trial

Background: Restenosis after percutaneous transluminal angioplasty (PTA) of the superficial femoral artery (SFA) may occur in 45% of patients at 2 years follow-up. Paclitaxel-coated balloons have been found to reduce neointimal hyperplasia, and thus reduce restenosis. Recently, the Legflow® paclitaxel-coated balloon (Cardionovum Sp.z.o.o., Warsaw, Poland) (LPEB) has been introduced. This balloon is covered with shellac, a Food and Drug Administration (FDA) approved natural resin, to obtain an equally distributed tissue concentration of paclitaxel. The RAPID trial is designed to assess restenosis after PTA using the Legflow balloon combined with nitinol stenting versus uncoated balloons with nitinol stenting in SFA lesions >5 cm.Methods/Design: A total of 176 adult patients with Rutherford class 2 to class 6 symptoms due to intermediate (5-15 cm) or long (>15 cm) atherosclerotic lesions in the SFA will be randomly allocated for treatment with LPEB with nitinol stenting or uncoated balloon angioplasty with stenting. Stenting will be performed using the Supera® stent in both groups (IDEV Technologies Inc., Webster, TX). The primary endpoint is the absence of binary restenosis of the treated SFA segment. Secondary outcomes are target lesion revascularization (TLR), clinical and hemodynamic outcome, amputation rate, mortality rate, adverse events, and device-specific adverse events. Follow up consists of four visits in which ankle-brachial indices (ABI), toe pressure measurements, and duplex ultrasound (DUS) will be performed. Furthermore, a peripheral artery questionnaire (PAQ) will be completed by the patients at each follow-up. In the event that DUS reveals a symptomatic >50% restenosis, or a >75% asymptomatic restenosis, additional digital subtraction angiography will be performed with any necessary re-intervention.Discussion: The RAPID trial is a multicenter randomized controlled patient blind trial that will provide evidence concerning whether the use of the Legflow paclitaxel/shellac coated balloons with nitinol stenting significantly reduces the frequency of restenosis in intermediate and long SFA lesions compared to standard PTA and stenting.Trial registration: ISRCTN47846578

A tomato xylem sap protein represents a new family of small cysteine-rich proteins with structural similarity to lipid transfer proteins

AbstractThe coding sequence of a major xylem sap protein of tomato was identified with the aid of mass spectrometry. The protein, XSP10, represents a novel family of extracellular plant proteins with structural similarity to plant lipid transfer proteins. The XSP10 gene is constitutively expressed in roots and lower stems. The decline of XSP10 protein levels in tomato infected with a fungal vascular pathogen may reflect breakdown or modification by the pathogen

The medicinal treatment of COVID-19:a brief update

Much has changed in the medical treatment of COVID-19 after the first patient with an infection with SARS-CoV-2 in the Netherlands was diagnosed in February 2020. On the basis of limited data, at first only off-label use of (hydroxy)chloroquine seemed to be a treatment option. However, now based on the findings of several randomized studies, other medicines have been included in the Dutch guidelines about the treatment of COVID-19. In this article, we will briefly discuss the current state of affairs with regard to the drugs (hydroxy) chloroquine, remdesivir and corticosteroids. Again, it appears that only well-executed randomized clinical trials can determine the status of various supposedly effective drugs.</p

A Self-organized model for network evolution

Here we provide a detailed analysis, along with some extensions and additonal investigations, of a recently proposed self-organised model for the evolution of complex networks. Vertices of the network are characterised by a fitness variable evolving through an extremal dynamics process, as in the Bak-Sneppen model representing a prototype of Self-Organized Criticality. The network topology is in turn shaped by the fitness variable itself, as in the fitness network model. The system self-organizes to a nontrivial state, characterized by a power-law decay of dynamical and topological quantities above a critical threshold. The interplay between topology and dynamics in the system is the key ingredient leading to an unexpected behaviour of these quantities

Calculation of The Band Gap Energy and Study of Cross Luminescence in Alkaline-Earth Dihalide Crystals

The band gap energy as well as the possibility of cross luminescence processes in alkaline-earth dihalide crystals have been calculated using the ab initio Perturbed-Ion (PI) model. The gap is calculated in several ways: as a difference between one-electron energy eigenvalues and as a difference between total energies of appropriate electronic states of the crystal, both at the HF level and with inclusion of Coulomb correlation effects. In order to study the possibility of ocurrence of cross luminescence in these materials, the energy difference between the valence band and the upmost core band for some representative crystals has been calculated. Both calculated band gap energies and cross luminescence predictions compare very well with the available experimental results.Comment: LaTeX file containing 8 pages plus 1 postscript figure. Final version accepted for publication in The Journal of the Physical Society of Japan. It contains a more complete list of references, as well as a more detailed comparison with previous theoretical investigations on the subjec

Supersonic water masers in 30 Doradus

We report on extremely high velocity molecular gas, up to -80 km/s relative to the ambient medium, in the giant star-formation complex 30 Doradus in the Large Magellanic Cloud (LMC), as observed in new 22 GHz H2O maser emission spectra obtained with the Mopra radio telescope. The masers may trace the velocities of protostars, and the observed morphology and kinematics indicate that current star formation occurs near the interfaces of colliding stellar-wind blown bubbles. The large space velocities of the protostars and associated gas could result in efficient mixing of the LMC. A similar mechanism in the Milky Way could seed the galactic halo with relatively young stars and gas.Comment: 11 pages plus 1 PS and 1 EPS figure, uses AASTeX preprint style; accepted for publication in Astrophysical Journal Letter