Expression of renal and intestinal Na/Pi cotransporters in the absence of GABARAP

We have recently shown that the abundance of the renal sodium (Na)/inorganic phosphate (Pi) cotransporter NaPi-IIa is increased in the absence of the GABA(A) receptor-associated protein (GABARAP). Accordingly, GABARAP-deficient mice have a reduced urinary excretion of Pi. However, their circulating levels of Pi do not differ from wild-type animals, suggesting the presence of a compensatory mechanism responsible for keeping serum Pi values constant. Here, we aimed first to identify the molecular basis of this compensation by analyzing the expression of Na/Pi cotransporters known to be expressed in the kidney and intestine. We found that, in the kidney, the upregulation of NaPi-IIa is not accompanied by changes on the expression of either NaPi-IIc or PiT2, the other cotransporters known to participate in renal Pi reabsorption. In contrast, the intestinal expression of NaPi-IIb is downregulated in mutant animals, suggesting that a reduced intestinal absorption of Pi could contribute to maintain a normophosphatemic status despite the increased renal retention. The second goal of this work was to study whether the alterations on the expression of NaPi-IIa induced by chronic dietary Pi are impaired in the absence of GABARAP. Our data indicate that, in response to high Pi diets, GABARAP-deficient mice downregulate the expression of NaPi-IIa to levels comparable to those seen in wild-type animals. However, in response to low Pi diets, the upregulation of NaPi-IIa is greater in the mutant mice. Thus, both the basal expression and the dietary-induced upregulation of NaPi-IIa are increased in the absence of GABARAP

Surface specific peptide immobilization on radiografted polymers as potential screening assays for antiangiogenic immunotherapy

International audienceAngiogenesis is a key process of cancer development and metastasis. It's inhibition is an important and promising strategy to block tumor growth and invasion. One of these approaches, based on antiangiogenic immunotherapy, is the recognition of a specific region of an angiogenic growth factor, called VEGF-A, by monoclonal antibodies. Thus, we aimed to design a novel assay to screen potential monoclonal antibodies directed against VEGF-A. In a first approach, we chose to perform covalent coupling of angiogenesis active cyclopeptides onto biocompatible thermoplastic transparent PVDF films and to fully characterize the chemical structure, the surface state and the biochemical properties of the synthesized devices. Electron beam radiation created radical sites on PVDF films without adding any toxic chemicals. These primary radicals and some induced peroxides were used as initiators for acrylic acid polymerization. Under our experimental conditions, surface grafting was favoured. Functionalization of PVDF-g-PAA films with peptides via a spacer arm was possible by performing two subsequent coupling reactions. EDC was used as coupling agent. Spacer arm saturation of the film surface was achieved for 25 mol% yield meaning that one spacer arm on four carboxylic acids were covalently bound. Peptide immobilization resulted in binding 10 times less leading to a final 3 mol% yield. Binding densities are governed by their individual space requirements. Each chemical step has been followed by FTIR in ATR mode, NMR using HR MAS technique and XPS. From XPS results, a layer of peptide covered PVDF-g-PAA film surface. The amounts of covalently immobilized peptide were determined using indirect UV spectroscopy on supernatant reaction solution. Yields were correlated with high resolution NMR results. The peptide/antibody recognition validated our system showing the conservation of peptide tridimensional structure with a positive response to specific antibodies. Because of the covalent protein linkage to PVDF films, a simple cleaning with immunoaffinity chromatography buffer allows the films to be reused

Eulerian simulation of the fluid dynamics of helicopter brownout

A computational model is presented that can be used to simulate the development of the dust cloud that can be entrained into the air when a helicopter is operated close to the ground in desert or dusty conditions. The physics of this problem, and the associated pathological condition known as ‘brownout’ where the pilot loses situational awareness as a result of his vision being occluded by dust suspended in the flow around the helicopter, is acknowledged to be very complex. The approach advocated here involves an approximation to the full dynamics of the coupled particulate-air system. Away from the ground, the model assumes that the suspended particles remain in near equilibrium under the action of aerodynamic forces. Close to the ground, this model is replaced by an algebraic sublayer model for the saltation and entrainment process. The origin of the model in the statistical mechanics of a distribution of particles governed by aerodynamic forces allows the validity of the method to be evaluated in context by comparing the physical properties of the suspended particulates to the local properties of the flow field surrounding the helicopter. The model applies in the Eulerian frame of reference of most conventional Computational Fluid Dynamics codes and has been coupled with Brown’s Vorticity Transport Model. Verification of the predictions of the coupled model against experimental data for particulate entrainment and transport in the flow around a model rotor are encouraging. An application of the coupled model to analyzing the differences in the geometry and extent of the dust clouds that are produced by single main rotor and tandem-rotor configurations as they decelerate to land has shown that the location of the ground vortex and the size of any regions of recirculatory flow, should they exist, play a primary role in governing the extent of the dust cloud that is created by the helicopter

Cooperative damping mechanism of the resonance in the nuclear photoabsorption

We propose a resonance damping mechanism to explain the disappearance of the peaks around the position of the resonances higher than the $\Delta$ resonance in the nuclear photoabsorption. This phenomenon is understood by taking into account the cooperative effect of the collision broadening of $\Delta$ and $N^{*}$, the pion distortion and the interference in the two-pion photoproduction processes in the nuclear medium.Comment: 11 pages, uses revtex.sty. To appear in Phys. Rev. Let

Two-dimensional discrete wavelet analysis of multiparticle event topology in heavy ion collisions

The event-by-event analysis of multiparticle production in high energy hadron and nuclei collisions can be performed using the discrete wavelet transformation. The ring-like and jet-like structures in two-dimensional angular histograms are well extracted by wavelet analysis. For the first time the method is applied to the jet-like events with background simulated by event generators, which are developed to describe nucleus-nucleus collisions at LHC energies. The jet positions are located quite well by the discrete wavelet transformation of angular particle distribution even in presence of strong background.Comment: 6 pages, 6 figure

Thermoelectric spin voltage in graphene

In recent years, new spin-dependent thermal effects have been discovered in ferromagnets, stimulating a growing interest in spin caloritronics, a field that exploits the interaction between spin and heat currents. Amongst the most intriguing phenomena is the spin Seebeck effect, in which a thermal gradient gives rise to spin currents that are detected through the inverse spin Hall effect. Non-magnetic materials such as graphene are also relevant for spin caloritronics, thanks to efficient spin transport, energy-dependent carrier mobility and unique density of states. Here, we propose and demonstrate that a carrier thermal gradient in a graphene lateral spin valve can lead to a large increase of the spin voltage near to the graphene charge neutrality point. Such an increase results from a thermoelectric spin voltage, which is analogous to the voltage in a thermocouple and that can be enhanced by the presence of hot carriers generated by an applied current. These results could prove crucial to drive graphene spintronic devices and, in particular, to sustain pure spin signals with thermal gradients and to tune the remote spin accumulation by varying the spin-injection bias

Isolated recessive nail dysplasia caused by <i>FZD6 </i>mutations:report of three families and review of the literature

Congenital abnormalities of the nail are rare conditions that are most frequently associated with congenital ectodermal syndromes involving several of the epidermal appendages including the skin, teeth, hair and nails. Isolated recessive nail dysplasia (IRND) is much rarer but has recently been recognized as a condition resulting in 20‐nail dystrophy in the absence of other cutaneous or extracutaneous findings. A few case reports have identified mutations in the Frizzled 6 (FZD6) gene in families presenting with abnormal nails consistent with IRND. These reports have highlighted the role of Wnt–FZD signalling in the process of nail formation. We report three families presenting with features of IRND, in whom we identified mutations in FZD6, including one previously unreported mutation

Lattice permutations and Poisson-Dirichlet distribution of cycle lengths

We study random spatial permutations on Z^3 where each jump x -> \pi(x) is penalized by a factor exp(-T ||x-\pi(x)||^2). The system is known to exhibit a phase transition for low enough T where macroscopic cycles appear. We observe that the lengths of such cycles are distributed according to Poisson-Dirichlet. This can be explained heuristically using a stochastic coagulation-fragmentation process for long cycles, which is supported by numerical data.Comment: 18 pages, 14 figure

Fantasies of subjugation: a discourse theoretical account of British policy on the European Union

The decision by the UK government to hold a referendum on Britain’s membership of the European Union (EU) marks an important development in policy towards the EU. Policy changes of this kind must be understood in the historical and political context in which they occur. This includes the framing of the policy issues within public discourse. In the UK, policies are formed in a discursive environment which is overwhelmingly hostile towards the EU. Debates are structured by a predominantly Euroskeptic discourse which emphasizes the UK’s separation and heterogeneity from the rest of the EU. Drawing on the logics of critical explanation, this article examines the structure and affective power of Euroskeptic discourses which dictate the terms of the EU debate. It presents a case study of the recent EU treaty revision process, culminating in the Treaty of Lisbon. In so doing, it enables a deeper understanding of recent policy developments