Na+/K+-ATPase is a new interacting partner for the neuronal glycine transporter GlyT2 that downregulates its expression in vitro and in vivo

The neuronal glycine transporter GlyT2 plays a fundamental role in the glycinergic neurotransmission by recycling the neurotransmitter to the presynaptic terminal. GlyT2 is the main supplier of glycine for vesicle refilling, a process that is absolutely necessary to preserve quantal glycine content in synaptic vesicles. Alterations in GlyT2 activity modify glycinergic neurotransmission and may underlie several neuromuscular disorders, such as hyperekplexia, myoclonus, dystonia, and epilepsy. Indeed, mutations in the gene encoding GlyT2 are the main presynaptic cause of hyperekplexia in humans and produce congenital muscular dystonia type 2 (CMD2) in Belgian Blue cattle. GlyT2 function is strictly coupled to the sodium electrochemical gradient actively generated by the Na+/K+-ATPase (NKA). GlyT2 cotransports 3Na+/Cl-/glycine generating large rises of Na+ inside the presynaptic terminal that must be efficiently reduced by the NKA to preserve Na+ homeostasis. In this work, we have used high-throughput mass spectrometry to identify proteins interacting with GlyT2 in the CNS. NKA was detected as a putative candidate and through reciprocal coimmunoprecipitations and immunocytochemistry analyses the association between GlyT2 and NKA was confirmed. NKA mainly interacts with the raft-associated active pool of GlyT2, and low and high levels of the specific NKA ligand ouabain modulate the endocytosis and total expression of GlyT2 in neurons. The ouabain-mediated downregulation of GlyT2 also occurs in vivo in two different systems: zebrafish embryos and adult rats, indicating that this NKA-mediated regulatory mechanism is evolutionarily conserved and may play a relevant role in the physiological control of inhibitory glycinergic neurotransmission

A selective metasurface absorber with an amorphous carbon interlayer for solar thermal applications

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordData availability: Data shown in this paper is accessible via the University of Bristol data repository: 10.5523/bris.11twobtdyxfs1ib2fxhlvn107This paper presents fabrication, measurement and modelling results for a metal-dielectric-metal metasurface absorber for solar thermal applications. The structure uses amorphous carbon as an inter-layer between thin gold films with the upper film patterned with a 2D periodic array using focused ion beam etching. The patterned has been optimised to give high absorptance from 400-1200nm and low absorptance above this wavelength range to minimise thermal radiation and hence obtain higher temperature performance. Wide angle absorptance results are shown and detailed modelling of a realistic nanostructured upper layer results in excellent agreement between measured and modelled results. The use of gold in this paper is a first step towards a high temperature metasurface where gold can be replaced by other refractory metals such as tungsten or chrome.Engineering and Physical Sciences Research Council (EPSRC

Focal, remote-controlled, chronic chemical modulation of brain microstructures

Direct delivery of fluid to brain parenchyma is critical in both research and clinical settings. This is usually accomplished through acutely inserted cannulas. This technique, however, results in backflow and significant dispersion away from the infusion site, offering little spatial or temporal control in delivering fluid. We present an implantable, MRI-compatible, remotely controlled drug delivery system for minimally invasive interfacing with brain microstructures in freely moving animals. We show that infusions through acutely inserted needles target a region more than twofold larger than that of identical infusions through chronically implanted probes due to reflux and backflow. We characterize the dynamics of in vivo infusions using positron emission tomography techniques. Volumes as small as 167 nL of copper-64 and fludeoxyglucose labeled agents are quantified. We further demonstrate the importance of precise drug volume dosing to neural structures to elicit behavioral effects reliably. Selective modulation of the substantia nigra, a critical node in basal ganglia circuitry, via muscimol infusion induces behavioral changes in a volume-dependent manner, even when the total dose remains constant. Chronic device viability is confirmed up to 1-y implantation in rats. This technology could potentially enable precise investigation of neurological disease pathology in preclinical models, and more efficacious treatment in human patients. Keywords: brain; drug delivery; substantia nigra; neural implant; PETNational Institutes of Health (U.S.) (Grant R01 EB016101)National Institute of Biomedical Imaging and Bioengineering (U.S.) (Grant R01 EB016101)National Cancer Institute (U.S.) (Grant P30-CA14051

Vector field and rotational curves in dark galactic halos

We study equations of a non-gauge vector field in a spherically symmetric static metric. The constant vector field with a scale arrangement of components: the time component about the Planck mass m_{Pl} and the radial component about M suppressed with respect to the Planck mass, serves as a source of metric reproducing flat rotation curves in dark halos of spiral galaxies, so that the velocity of rotation v_0 is determined by the hierarchy of scales: \sqrt{2} v_0^2= M/m_{Pl}, and M\sim 10^{12} GeV. A natural estimate of Milgrom's acceleration about the Hubble rate is obtained.Comment: 17 pages, iopart style, misprint remove

Estudio de identificacion de zonas de riesgos en los distritos 5 y 6 de la ciudad de El Alto : construccion de los mapas y comentarios

Dans le cadre d'un projet DIPECHO du Département d'aide humanitaire de la Commission européenne, l'équipe du programme PACIVUR de l'IRD a été chargée d'identifier les zones à risques de deux des onze districts qui composent El Alto. L'identification de ces zones à risques doit fournir les éléments pour mettre en œuvre une meilleure préparation face aux désastres possibles. Elle implique donc de connaître à la fois les processus physiques à l'origine de menaces, les éléments qu'elles peuvent endommager et qui provoquent le désastre, ainsi que les éléments utiles à la gestion de la crise éventuelle qui en découl