A System for Performing High Throughput Assays of Synaptic Function

Unbiased, high-throughput screening has proven invaluable for dissecting complex biological processes. Application of this general approach to synaptic function would have a major impact on neuroscience research and drug discovery. However, existing techniques for studying synaptic physiology are labor intensive and low-throughput. Here, we describe a new high-throughput technology for performing assays of synaptic function in primary neurons cultured in microtiter plates. We show that this system can perform 96 synaptic vesicle cycling assays in parallel with high sensitivity, precision, uniformity, and reproducibility and can detect modulators of presynaptic function. By screening libraries of pharmacologically defined compounds on rat forebrain cultures, we have used this system to identify novel effects of compounds on specific aspects of presynaptic function. As a system for unbiased compound as well as genomic screening, this technology has significant applications for basic neuroscience research and for the discovery of novel, mechanism-based treatments for central nervous system disorders

Benchmark performance of low-cost Sb2Se3 photocathodes for unassisted solar overall water splitting

Determining cost-effective semiconductors exhibiting desirable properties for commercial photoelectrochemical water splitting remains a challenge. Herein, we report a Sb2Se3 semiconductor that satisfies most requirements for an ideal high-performance photoelectrode, including a small band gap and favourable cost, optoelectronic properties, processability, and photocorrosion stability. Strong anisotropy, a major issue for Sb2Se3, is resolved by suppressing growth kinetics via close space sublimation to obtain high-quality compact thin films with favourable crystallographic orientation. The Sb2Se3 photocathode exhibits a high photocurrent density of almost 30mAcm(-2) at 0V against the reversible hydrogen electrode, the highest value so far. We demonstrate unassisted solar overall water splitting by combining the optimised Sb2Se3 photocathode with a BiVO4 photoanode, achieving a solar-to-hydrogen efficiency of 1.5% with stability over 10h under simulated 1 sun conditions employing a broad range of solar fluxes. Low-cost Sb2Se3 can thus be an attractive breakthrough material for commercial solar fuel production. While photoelectrochemical water splitting offers an integrated means to convert sunlight to a renewable fuel, cost-effective light-absorbers are rare. Here, authors report Sb2Se3 photocathodes for high-performance photoelectrochemical water splitting devices

A new method for studying activity and reaction kinetics of photocatalytic water oxidation systems using a bubbling reactor

A novel method is proposed for studying kinetics and overall activity of water oxidation (WO) catalysts using a bubbling reactor, where oxygen concentration is measured simultaneously in the liquid and in the gaseous phase. Total oxygen evolution is obtained from direct integration. The actual rate of oxygen formation as a function of time, RO2(t) not accessible to direct measurement with batch reactors, is calculated from raw data through a simple but comprehensive mathematical model, taking into account mass transfer phenomena occurring in the system. Data concerning the activity of a nanostructured Co3O4 catalyst dispersed on a mesoporous silica (MSU-H), in the presence of tris(2,2'-bipyridyl)Ruthenium [Ru(bpy)3]2+ as sensitizer and Na2S2O8 as sacrificial reactant, are used to illustrate data processing. Behaviour of the system is complicated by the occurrence, besides WO reaction, of the degradation of the sensitizer. Increase of sweeping gas flow increases RO2(t), by decreasing diffusional limitations to the reactions in the system: conditions for minimizing those were established. Data reported show that the assumption generally made of equilibrium between gaseous and liquid phase through Henry's law is incorrect, the more so the smaller the apparent mass transfer coefficient, kLa. An additional reason for removing oxygen from the liquid phase through bubbling is the occurrence of a parasitic reaction of molecular oxygen with the sensitizer. The method seems to yield reliable values of both kLa and the set of RO2(t) values: the former scales with the flow of sweeping gas, as expected; RO2(t) curves are in qualitative agreement with accepted reaction mechanisms. Results concerning RO2(t) lend support to our previous kinetic studies (M. Armandi et. al., ACS Catal. 2013, 3, 1272) where the reaction rate was assumed as constant for the first ~ 15 min. Availability of RO2(t) data not too biased by diffusional limitations opens the way to realistic studies of the kinetic features of WO heterogeneous reactions, in the present case as well as in many other

Atomically dispersed nickel-nitrogen-sulfur species anchored on porous carbon nanosheets for efficient water oxidation

Developing low-cost electrocatalysts to replace precious Ir-based materials is key for oxygen evolution reaction (OER). Here, we report atomically dispersed nickel coordinated with nitrogen and sulfur species in porous carbon nanosheets as an electrocatalyst exhibiting excellent activity and durability for OER with a low overpotential of 1.51 V at 10 mA cm(-2) and a small Tafel slope of 45 mV dec(-1) in alkaline media. Such electrocatalyst represents the best among all reported transition metal- and/or heteroatom-doped carbon electrocatalysts and is even superior to benchmark Ir/C. Theoretical and experimental results demonstrate that the well-dispersed molecular S vertical bar NiNx species act as active sites for catalyzing OER. The atomic structure of S vertical bar NiNx centers in the carbon matrix is clearly disclosed by aberration-corrected scanning transmission electron microscopy and synchrotron radiation X-ray absorption spectroscopy together with computational simulations. An integrated photoanode of nanocarbon on a Fe2O3 nanosheet array enables highly active solar-driven oxygen production

A roadmap of strain in doped anatase TiO2

Anatase titanium oxide is important for its high chemical stability and photocatalytic properties, however, the latter are plagued by its large band gap that limits its activity to only a small percentage of the solar spectrum. In that respect, straining the material can reduce its band gap increasing the photocatalytic activity of titanium oxide. We apply density functional theory with the introduction of the Hubbard + U model, to investigate the impact of stress on the electronic structure of anatase in conjunction with defect engineering by intrinsic defects (oxygen/titanium vacancies and interstitials), metallic dopants (iron, chromium) and non-metallic dopants (carbon, nitrogen). Here we show that both biaxial and uniaxial strain can reduce the band gap of undoped anatase with the use of biaxial strain being marginally more beneficial reducing the band gap up to 2.96 eV at a tensile stress of 8 GPa. Biaxial tensile stress in parallel with doping results in reduction of the band gap but also in the introduction of states deep inside the band gap mainly for interstitially doped anatase. Dopants in substitutional positions show reduced deep level traps. Chromium-doped anatase at a tensile stress of 8 GPa shows the most significant reduction of the band gap as the band gap reaches 2.4 eV

Contribution of the Type VI Secretion System Encoded in SPI-19 to Chicken Colonization by Salmonella enterica Serotypes Gallinarum and Enteritidis

Salmonella Gallinarum is a pathogen with a host range specific to poultry, while Salmonella Enteritidis is a broad host range pathogen that colonizes poultry sub-clinically but is a leading cause of gastrointestinal salmonellosis in humans and many other species. Despite recent advances in our understanding of the complex interplay between Salmonella and their hosts, the molecular basis of host range restriction and unique pathobiology of Gallinarum remain largely unknown. Type VI Secretion System (T6SS) represents a new paradigm of protein secretion that is critical for the pathogenesis of many Gram-negative bacteria. We recently identified a putative T6SS in the Salmonella Pathogenicity Island 19 (SPI-19) of Gallinarum. In Enteritidis, SPI-19 is a degenerate element that has lost most of the T6SS functions encoded in the island. In this work, we studied the contribution of SPI-19 to the colonization of Salmonella Gallinarum strain 287/91 in chickens. Non-polar deletion mutants of SPI-19 and the clpV gene, an essential T6SS component, colonized the ileum, ceca, liver and spleen of White Leghorn chicks poorly compared to the wild-type strain after oral inoculation. Return of SPI-19 to the ΔSPI-19 mutant, using VEX-Capture, complemented this colonization defect. In contrast, transfer of SPI-19 from Gallinarum to Enteritidis resulted in transient increase in the colonization of the ileum, liver and spleen at day 1 post-infection, but at days 3 and 5 post-infection a strong colonization defect of the gut and internal organs of the experimentally infected chickens was observed. Our data indicate that SPI-19 and the T6SS encoded in this region contribute to the colonization of the gastrointestinal tract and internal organs of chickens by Salmonella Gallinarum and suggest that degradation of SPI-19 T6SS in Salmonella Enteritidis conferred an advantage in colonization of the avian host