Assembly, trafficking and function of a1ß2y2 GABA(A) receptors are regulated by N-terminal regions, in a subunit-specific manner

GABAA receptors are pentameric ligand-gated ion channels (pLGIC) that mediate inhibitory fast synaptic transmission in the central nervous system. Consistent with recent pLGIC structures, sequence analysis predicts an α-helix near the N-terminus of each GABAA receptor subunit. Preceding each α-helix are 8-36 additional residues, which we term the Nterminal extension. In homomeric GABAC receptors and nicotinic acetylcholine receptors (nAChR), the N-terminal α-helix is functionally essential. Here we determined the role of the N-terminal extension and putative α-helix in heteromeric α1β2γ2 GABAA receptors. This role was most prominent in the α1 subunit, with deletion of the N-terminal extension or further deletion of the putative α-helix both dramatically reduced the number of functional receptors at the cell surface. Conversely, deletion of the β2 or γ2 N-terminal extension had little effect on the number of functional cell-surface receptors. Additional deletion of the putative α-helix in the β2 or γ2 subunits did, however, decrease both functional cell surface receptors and incorporation of the γ2 subunit into mature receptors. In the β2 subunit only, α-helix deletions affected GABA sensitivity and desensitization. Our findings demonstrate that N-terminal extensions and α-helices make key subunit-specific contributions to assembly, consistent with both regions being involved in inter-subunit interactions

Surface characterization of selected LDEF tray clamps

The surface characterization of chromic acid anodized 6061-T6 aluminum alloy tray clamps has shown differences in surface chemistry depending upon the position on the Long Duration Exposure Facility (LDEF). Water contact angle results showed no changes in wettability of the tray clamps. The overall surface topography of the control, trailing edge(E3) and leading edge(D9) samples was similar. The thickness of the aluminum oxide layer for all samples determined by Auger depth profiling was less than one micron. X-ray photoelectron spectroscopy (XPS) analysis of the tray clamps showed significant differences in the surface composition. Carbon and silicon containing compounds were the primary contaminants detected

Development and Persistence of 'Static' or 'Dead' Zones in Flows

Certain ceramic products are formed through extrusion processes, where a slurry is forced through small openings to form such products as filters. At the top is a large tank. The slurry is forced through the tank into an extrusion chamber, and then out through slots to form the finished product. [The slurry may be thought of as a mixture of clay (or other polymers), water, and other binders. There are many ways to model this mixture, some of which will be discussed in this report. For instance, the slurry can be modeled as a non-Newtonian fluid, a two-phase flow with liquid and solids, or a viscoelastic fluid. One can also model the mixture as an elongated particle suspension in water, where changes in the orientation of the particles could affect the flow.] After the extrusion process is complete, one finds that ‘dead zones’ of dry paste accumulate in two areas. Most prominently, they occur at the lower corners of the tank. They also occur on the floor of the extrusion chamber near the slots, both near and away from the walls. Since we will consider wall effects in the tank, for the extrusion chamber we consider only flow cells sufficiently far away from the walls. Then we may exploit the periodic nature of the device and consider only a single flow cell. The aim of this project is to determine the formation mechanisms of these dead zones, and see how they affect the overall flow

Experimental study of photon beam polarimeter based on nuclear e+e- pair production in an amorphous target

The experimental method of the linearly polarized photons polarimetry,using incoherent e+e- pair production process has been investigated on the beam of coherent bremsstrahlung (CB) photons in the energy range of 0.9-1.1 GeV at the Yerevan synchrotron.Comment: 6 pages (text),10 figure

A loss-of-function polymorphism in the human P2X4 receptor is associated with increased pulse pressure

The P2X4 receptor is involved in endothelium-dependent changes in large arterial tone in response to shear stress and is, therefore, potentially relevant to arterial compliance and pulse pressure. Four identified nonsynonymous polymorphisms in P2RX4 were reproduced in recombinantly expressed human P2X4. Electrophysiological studies showed that one of these, the Tyr315>Cys mutation (rs28360472), significantly reduced the peak amplitude of the ATP-induced inward current to 10.9% of wild-type P2X4 receptors in transfected HEK-293 cells (10 µmol/L of ATP; n=4-8 cells; P<0.001). Concentration-response curves for ATP and the partial agonist BzATP demonstrate that the 315Cys-P2X4 mutant had an increased EC50 value for both ligands. Mutation of Tyr315>Cys likely disrupts the agonist binding site of P2X4 receptors, a finding supported by molecular modeling based on the zebrafish P2X4 receptor crystal structure. We tested inheritance of rs28360472 encoding the Tyr315>Cys mutation in P2RX4 against pulse pressure in 2874 subjects from the Victorian Family Heart Study. The minor allele frequency was 0.014 (1.4%). In a variance components analysis we found significant association with pulse pressure (P=0.023 for total association) where 1 minor allele increased pulse pressure by 2.84 mm Hg (95% CI: 0.41-5.27). This increase in pulse pressure associated with inheritance of 315Cys-P2X4 receptors might reflect reduced large arterial compliance as a result of impaired endothelium-dependent vasodilation in large arteries

A multi-object fiber spectrograph for The Hale Telescope

A new faint-object spectrograph has been designed around the capabilities of fiber optics. This instrument, the Norris Spectrograph, is for exclusive use at the Cassegrain focus (f/16) of The Hale Telescope and is optimized for faint galaxy spectroscopy. There are 176 independently positionable fibers that are serially manipulated by a single robotic system. Each of these fibers sees 1.6 arcsec on the sky and the total positionable area is in excess of 300 arcmin^2. Unlike most multiobject spectrographs which utilize fibers that are several tens of meters long, the philosophy of the design of the Norris was quite the antithesis, i.e., to minimize the fiber lengths; hence, it is an entirely self-contained telescope-mounted instrument for the Cassegrain focus. The instrument consists of an integrated xy stage, for the fiber positioning, and an attached optical spectrograph. The design of the spectrograph is basically classical: spherical collimator mirror, standard reflection grating, and a newly designed all-transmissive-optics camera lens. The detector currently used is a thinned, AR-coated 2048 X 2048 Tektronix CCD. Fibers are arranged in two linear opposing banks that can access the 20 arcmin diameter field-of-view (FOV) of the instrument. The accuracy of fiber placement (assuming errorless coordinates) is less than 0.1 arcsec over the entire FOV. Fibers may be placed as close as 16 arcsec. This permits close pairings of fibers for very faint-object spectroscopy. Beam switching between paired fibers, as was done with two-channel spectrographs of yesteryear, will help average out temporal and spatial variations of the light of the night sky. Actual observations performed in this mode of operation indicate that the quality of the sky subtraction improves, as would be expected. The density of paired fibers within the Norris FOV matches the approximate density of faint field galaxies expected to a blue magnitude of 21. Software exists to take object lists (α,δ) and convert them to rectilinear (x,y) values (mm) on the xy stage by gnomonic projection and to assign fibers. This software also corrects for precession of the equinoxes, proper motion if epoch differences exist, and corrects for differential atmospheric refraction. To place a single fiber takes approximately 5 s on the average. A lower limit to the efficiency of the spectrograph plus telescope has been estimated to be 6.8% at 5500 Å. In order to derive the throughput of the instrument, the efficiency of the telescope, estimated to be approximately 56%, must be divided out. This value is consistent with the expectation that the reduction in efficiency from that of a standard CCD spectrograph such as The Hale Telescope's Double Spectrograph will be about a factor of 2. This results from the 60%-70% transmittance of the fibers and other losses. The spectra produced are linear with little distortion. With 10 A spectral resolution, fitting residuals on the order of 100 km s^(-1) are easily obtainable by modeling the dispersion by a third-order polynomial. The resolutions currently available range from 1 to about 20 Å. The spectra have a FWHM in the direction perpendicular to that of the dispersion of about 90 µm, or equivalently about three 27 pixels found in the older Tektronix 2048 CCDs. The interorder spacing of 250 µm is large enough to permit clean spectrum extractions. The instrument has been in use for several years. The scientific programs vary from high resolution (1 Å resolution) spectroscopy of stars in nearby globular clusters to a low spectral resolution (10 Å) survey of faint field galaxies. In this latter survey, with typical 2-hr exposures, absorption-line redshifts as high as z ~ 0.5 have been routinely measured. Several heretofore unknown quasars with redshifts around three have also been discovered serendipitously

SeaWiFS Postlaunch Technical Report Series

The SeaWiFS Transfer Radiometer (SXR) was built for the Sea-viewing Wide Field-of-view Sensor (SeaWiFS) Project as part of an Interagency Agreement with the National Aeronautics and Space Administration (NASA). The SXR is a multichannel radiometer designed to verify and compare measurements of spectral radiance at six discrete wavelengths in the visible and near infrared for various calibration sources in the SeaWiFS Project. In addition, the SXR is used to compare these sources to standards of spectral radiance maintained at the National Institute of Standards and Technology (NIST). The SXR was designed, built, and thoroughly characterized in the Optical Technology Division at NIST. A unique optical design provides six independent optical paths, each equipped with a temperature stabilized interference filter and silicon photodiode. A separate beam path through the input lens is used to visually align the SXR. The entrance windows for each channel overlap at the source, with each channel sampling a unique solid angle within the field of view of the SXR; this allows for simultaneous sampling of all channels. The combined standard relative uncertainty of spectral radiance measurements with the SXR is estimated to be between 0.6% and 1.3%. This report describes the design and construction of the SXR in detail, and gives the results of the optical characterization and calibrations done at NIST. The SXR has been used for several intercomparisons which include several SeaWiFS Intercalibration Round-Robin Experiments (SIRREXs); those done at the Marine Optical Buoy (MOBY) laboratories in Honolulu, Hawaii; at the NEC Corporation in Yokohama, Japan; and Orbital Sciences Corporation (OSC) in Germantown, Maryland. Thorough optical characterization and calibration of the SXR was essential to the successful application of the radiometer for these measurements

An investigation of traumatic life events and obsessive-compulsive disorder.

Abstract Obsessive-compulsive disorder (OCD), like most other psychiatric disorders, is suspected of being influenced by an interaction between life events and genes, both with regard to onset and course of illness. To date, no specific genes have been identified as playing a frequent role, and only a relatively few empirical studies have assessed the association between stressful life events (SLEs) and OCD. The present study builds on past research by examining the potential contributions from traumatic life events (TLEs) on the severity and symptom features in 265 individuals with Structured Clinical Interview for DSM-IV (SCID)-diagnosed OCD. Of these participants 54% endorsed having experienced at least one TLE in their life time. The presence of one or more TLEs was associated with increased OCD symptom severity. This relationship remained significant despite controlling for key variables including age, OCD age-of-onset, comorbidity, and depressive symptoms. In addition, obsessions/checking and symmetry/ordering were two of four symptom factors that were specifically associated with the occurrence of TLEs. These results are generally supportive of a pathoplastic relationship between TLEs and OCD symptomatology and thus suggest the need for greater systematic consideration of life stresses in research focused on the nature and treatment of OCD.