The neurotoxicity of sulfur-containing amino acids in energy-deprived rat hippocampal slices

The rat hippocampal slice preparation and its electrophysiology were used to assess the toxicity of two sulfur-containing amino acids, L-cysteate (CA) and L-cysteine (CYS). Both compounds were innocuous under normal conditions but became toxic in energy-deprived (lack of oxygen or glucose) slices. CA and CYS toxicity was apparent as both reduced the number of slices that normally recover their neuronal function (evoked CA1 population spike) after a standardized period of hypoxia or glucose deprivation (GD). The competitive N-methyl-D-aspartate (NMDA) antagonist DL-2-amino-5-phosphonovalerate blocked the toxicity of both CA and CYS in hypoxic slices, but it was effective only against CYS toxicity in glucose-deprived slices. The glycine antagonist 7-chlorokynurenate blocked CA and CYS toxicity in hypoxic slices but was unable to block their toxicity in glucose-deprived tissue. Perfusing slices with medium containing a high magnesium concentration blocked the toxicity of CA in both hypoxic and glucose-deprived slices, a treatment that was ineffective against CYS toxicity under either condition. Calcium depletion from the perfusion medium completely blocked the damaging effect of both amino acids in hypoxic slices, but it only partially blocked the toxicity of CA and did not block that of CYS in glucose-deprived slices. These results suggest that CA and CYS activate different NMDA receptor subsets and other glutamate receptor subtypes. Moreover, the results indicate a possible difference between the mechanism that lead to hypoxic neuronal damage and the one that lead to hypoglycemic neuronal damage.     

The cultural construction of self-enhancement: An examination of group-serving biases.

Self-serving biases, found routinely in Western samples, have not been observed in Asian samples. Yet given the orientation toward individualism and collectivism in these 2 cultures, respectively, it is imperative to examine whether parallel differences emerge when the target of evaluation is the group. It may be that Asians show a group-serving bias parallel to the Western self-serving bias. In 2 studies, group-serving biases were compared across European Canadian, Asian Canadian, and Japanese students. Study 1 revealed that Japanese students evaluated a family member less positively than did both groups of Canadian students. Study 2 replicated this pattern with students' evaluations of their universities. The data suggest that cultural differences in enhancement biases are robust, generalizing to individuals' evaluations of their groups. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Functional and Molecular Properties of DYT-SGCE Myoclonus-Dystonia Patient-Derived Striatal Medium Spiny Neurons

Myoclonus-dystonia (DYT-SGCE, formerly DYT11) is characterized by alcohol-sensitive, myoclonic-like appearance of fast dystonic movements. It is caused by mutations in the SGCE gene encoding ε-sarcoglycan leading to a dysfunction of this transmembrane protein, alterations in the cerebello-thalamic pathway and impaired striatal plasticity. To elucidate underlying pathogenic mechanisms, we investigated induced pluripotent stem cell (iPSC)-derived striatal medium spiny neurons (MSNs) from two myoclonus-dystonia patients carrying a heterozygous mutation in the SGCE gene (c.298T>G and c.304C>T with protein changes W100G and R102X) in comparison to two matched healthy control lines. Calcium imaging showed significantly elevated basal intracellular Ca²⁺ content and lower frequency of spontaneous Ca²⁺ signals in SGCE MSNs. Blocking of voltage-gated Ca²⁺ channels by verapamil was less efficient in suppressing KCl-induced Ca²⁺ peaks of SGCE MSNs. Ca²⁺ amplitudes upon glycine and acetylcholine applications were increased in SGCE MSNs, but not after GABA or glutamate applications. Expression of voltage-gated Ca²⁺ channels and most ionotropic receptor subunits was not altered. SGCE MSNs showed significantly reduced GABAergic synaptic density. Whole-cell patch-clamp recordings displayed elevated amplitudes of miniature postsynaptic currents and action potentials in SGCE MSNs. Our data contribute to a better understanding of the pathophysiology and the development of novel therapeutic strategies for myoclonus-dystonia.     

Passive Q Switching of a Diode-Pumped 946-nm Nd:YAG Laser with 1.6-W Average Output Power

As much as 1.6-W average output power was emitted in a simple setup from a diffusion-bonded Nd:YAG rod with 70-100-ns Q-switched pulses at 946 nm and repetition frequencies between 15 and 45 kHz at 22-W incident diode-pump power. A Cr(4+):YAG crystal with a bleachable loss of approximately 2.5% and a length of 0.5 mm was used as a saturable absorber. The extraction efficiency was 47% in comparison with the continuous-wave laser output power of 3.37 W in the free-running regime.     

Tunable single frequency thulium:YAG microchip laser with external feedback

By use of the reflection of an uncoated external etalon, a diode-pumped thulium-doped YAG microchip laser was forced into a single-frequency mode. The wavelength of the single-frequency radiation was tunable over 15 nm simply by translation of the etalon relative to the laser. Output powers of 45 mW were achieved in a monolithic setup that is insensitive to vibrations. The origin of the single-frequency oscillation is the wavelength-dependent reflection of the etalon, which is coupled back into the laser resonator. This method permits the combination of inherently stable, single-frequency resonator geometries such as microchips with laser materials that have broad tuning ranges.     

Fabrication and simulation of diffractive optical elements with superimposed antireflection subwavelength gratings

With the aim of reducing surface reflections and increasing the diffraction efficiency we investigated the superposition of subwavelength phase gratings onto blazed phase gratings. With direct-write electron-beam lithography bare blazed gratings and blazed gratings carrying subwavelength gratings were fabricated and their optical performances compared. For TE polarization the subwavelength-carrying gratings showed a maximum diffraction efficiency of 90.6%, whereas the corresponding maximum value for the bare grating was 86.3%. The experiment was simulated with rigorous diffraction theory.     

What are the consequences of the new American guidelines for the diagnosis of diabetes mellitus in The Netherlands?

Anaemia is a commonly encountered medical condition, although associated ophthalmic manifestations are not often sought or recognised. The authors present a case report of a patient with severe vitamin B12 deficiency anaemia with florid retinal changes classical of anaemic retinopathy. A review of the ocular involvement in anaemia is also presented.     

A parallel code for a self-consistent charge density functional based tight binding method: Total energy calculations for extended systems

We present a parallel version of a selfconsistent-charge density-functional based tight-binding (SCC-DFTB) method for total energy calculations and geometry optimizations of clusters and periodic structures. On single processor machines the SCC-DFTB method has been successfully applied to systems up to several hundred atoms with an accuracy comparable to sophisticated selfconsistent field density-functional theory (SCF-DFT) methods. The new parallel code allows to treat systems which are larger by an order of magnitude in reasonable time. The freely available ScaLAPACK and PBLAS libraries are used for linear algebra operations. We tested the scaling of our program for a realistic system (III–V semiconductor surface) with different sizes and give a short outlook on current applications.     

One Question,Multiple Answers: Biochemical and Biophysical Screening Methods Retrieve Deviating Fragment Hit Lists

Fragment‐based lead discovery is gaining momentum in drug development. Typically, a hierarchical cascade of several screening techniques is consulted to identify fragment hits which are then analyzed by crystallography. Because crystal structures with bound fragments are essential for the subsequent hit‐to‐lead‐to‐drug optimization, the screening process should distinguish reliably between binders and non‐binders. We therefore investigated whether different screening methods would reveal similar collections of putative binders. First we used a biochemical assay to identify fragments that bind to endothiapepsin, a surrogate for disease‐relevant aspartic proteases. In a comprehensive screening approach, we then evaluated our 361‐entry library by using a reporter‐displacement assay, saturation‐transfer difference NMR, native mass spectrometry, thermophoresis, and a thermal shift assay. While the combined results of these screening methods retrieve 10 of the 11 crystal structures originally predicted by the biochemical assay, the mutual overlap of individual hit lists is surprisingly low, highlighting that each technique operates on different biophysical principles and conditions.