The Ultraviolet Imaging Telescope: Instrument and Data Characteristics

The Ultraviolet Imaging Telescope (UIT) was flown as part of the Astro observatory on the Space Shuttle Columbia in December 1990 and again on the Space Shuttle Endeavor in March 1995. Ultraviolet (1200-3300 Angstroms) images of a variety of astronomical objects, with a 40 arcmin field of view and a resolution of about 3 arcsec, were recorded on photographic film. The data recorded during the first flight are available to the astronomical community through the National Space Science Data Center (NSSDC); the data recorded during the second flight will soon be available as well. This paper discusses in detail the design, operation, data reduction, and calibration of UIT, providing the user of the data with information for understanding and using the data. It also provides guidelines for analyzing other astronomical imagery made with image intensifiers and photographic film.Comment: 44 pages, LaTeX, AAS preprint style and EPSF macros, accepted by PAS

Ligand sensitivity of type-1 inositol 1,4,5-trisphosphate receptor is enhanced by the D2594K mutation.

Inositol 1,4,5-trisphosphate receptor (IP3R) and ryanodine receptor (RyR) are homologous cation channels that mediate release of Ca2+ from the endoplasmic/sarcoplasmic reticulum (ER/SR) and thereby are involved in many physiological processes. In previous studies, we determined that when the D2594 residue, located at or near the gate of the IP3R type 1, was replaced by lysine (D2594K), a gain of function was obtained. This mutant phenotype was characterized by increased IP3 sensitivity. We hypothesized the IP3R1-D2594 determines the ligand sensitivity of the channel by electrostatically affecting the stability of the closed and open states. To test this possibility, the relationship between the D2594 site and IP3R1 regulation by IP3, cytosolic, and luminal Ca2+ was determined at the cellular, subcellular, and single-channel levels using fluorescence Ca2+ imaging and single-channel reconstitution. We found that in cells, D2594K mutation enhances the IP3 ligand sensitivity. Single-channel IP3R1 studies revealed that the conductance of IP3R1-WT and -D2594K channels is similar. However, IP3R1-D2594K channels exhibit higher IP3 sensitivity, with substantially greater efficacy. In addition, like its wild type (WT) counterpart, IP3R1-D2594K showed a bell-shape cytosolic Ca2+-dependency, but D2594K had greater activity at each tested cytosolic free Ca2+ concentration. The IP3R1-D2594K also had altered luminal Ca2+ sensitivity. Unlike IP3R1-WT, D2594K channel activity did not decrease at low luminal Ca2+ levels. Taken together, our functional studies indicate that the substitution of a negatively charged residue by a positive one at the channels' pore cytosolic exit affects the channel's gating behavior thereby explaining the enhanced ligand-channel's sensitivity.The authors received the support of research grants from the National Institutes of Health grant/award numbers R01GM111397 to S. R. W. Chen, M. Fill, and J. Ramos‐Franco, R01HL057832 to M. Fill and by the Canadian Institutes of Health Research, grant/award number PJT‐173352. S. R. W. Chen holds the Heart and Stroke Foundation Chair in Cardiovascular Research (END611955). A. Tambeaux was supported by the Graduate College of Rush University Medical Center.S

Carisbamate Blockade of T-Type Voltage-Gated Calcium Channels

Objectives Carisbamate (CRS) is a novel monocarbamate compound that possesses antiseizure and neuroprotective properties. However, the mechanisms underlying these actions remain unclear. Here, we tested both direct and indirect effects of CRS on several cellular systems that regulate intracellular calcium concentration [Ca2+]i. Methods We used a combination of cellular electrophysiologic techniques, as well as cell viability, Store Overload‐Induced Calcium Release (SOICR), and mitochondrial functional assays to determine whether CRS might affect [Ca2+]i levels through actions on the endoplasmic reticulum (ER), mitochondria, and/or T‐type voltage‐gated Ca2+ channels. Results In CA3 pyramidal neurons, kainic acid induced significant elevations in [Ca2+]i and long‐lasting neuronal hyperexcitability, both of which were reversed in a dose‐dependent manner by CRS. Similarly, CRS suppressed spontaneous rhythmic epileptiform activity in hippocampal slices exposed to zero‐Mg2+ or 4‐aminopyridine. Treatment with CRS also protected murine hippocampal HT‐22 cells against excitotoxic injury with glutamate, and this was accompanied by a reduction in [Ca2+]i. Neither kainic acid nor CRS alone altered the mitochondrial membrane potential (ΔΨ) in intact, acutely isolated mitochondria. In addition, CRS did not affect mitochondrial respiratory chain activity, Ca2+‐induced mitochondrial permeability transition, and Ca2+ release from the ER. However, CRS significantly decreased Ca2+ flux in human embryonic kidney tsA‐201 cells transfected with Cav3.1 (voltage‐dependent T‐type Ca2+) channels. Significance Our data indicate that the neuroprotective and antiseizure activity of CRS likely results in part from decreased [Ca2+]i accumulation through blockade of T‐type Ca2+ channels

ß2-adrenergic stimulation potentiates spontaneous calcium release by increasing signal mass and co-activation of ryanodine receptor clusters

Aims: It is unknown how ß-adrenergic stimulation affects calcium dynamics in individual RyR2 clusters and leads to the induction of spontaneous calcium waves. To address this, we analysed spontaneous calcium release events in green fluorescent protein (GFP)-tagged RyR2 clusters. Methods: Cardiomyocytes from mice with GFP-tagged RyR2 or human right atrial tissue were subjected to immunofluorescent labelling or confocal calcium imaging. Results: Spontaneous calcium release from single RyR2 clusters induced 91.4% ± 2.0% of all calcium sparks while 8.0% ± 1.6% were caused by release from two neighbouring clusters. Sparks with two RyR2 clusters had 40% bigger amplitude, were 26% wider, and lasted 35% longer at half maximum. Consequently, the spark mass was larger in two- than one-cluster sparks with a median and interquartile range for the cumulative distribution of 15.7 ± 20.1 vs 7.6 ± 5.7 a.u. (P < .01). ß2-adrenergic stimulation increased RyR2 phosphorylation at s2809 and s2815, tripled the fraction of two- and three-cluster sparks, and significantly increased the spark mass. Interestingly, the amplitude and mass of the calcium released from a RyR2 cluster were proportional to the SR calcium load, but the firing rate was not. The spark mass was also higher in 33 patients with atrial fibrillation than in 36 without (22.9 ± 23.4 a.u. vs 10.7 ± 10.9; P = .015). Conclusions: Most sparks are caused by activation of a single RyR2 cluster at baseline while ß-adrenergic stimulation doubles the mass and the number of clusters per spark. This mimics the shift in the cumulative spark mass distribution observed in myocytes from patients with atrial fibrillation. Keywords: calcium spark; cardiac myocyte; confocal imaging; ryanodine receptor; sarcoplasmic reticulum; ß-adrenergic.This work was supported by grants from the Spanish Ministry of Science and Innovation PID2020-116927RB-C21 and SAF2017-88019-C3-1R (to LHM) and SAF2017-88019-C3-3R (to RB); from Fundació Marató TV3, Marato-2015-2030 (to LHM); from Generalitat de Catalunya SGR2017-1769 (to LHM); from the Natural Sciences and Engineering Research Council of Canada (to SRWC); from the Canadian Institutes of Health Research (to SRWC); from the Heart and Stroke Foundation Chair in Cardiovascular Research (to SRWC), and from Spanish Ministry of Health and Consume CB16/11/00276 (to JC). SC was the recipient of a predoctoral grant (FPU18/01250) from the Spanish Ministry of Science and Innovation, and AL received a PERIS SALUT-16 grant from Generalitat de Catalunya

ARVC-Related Mutations in Divergent Region 3 Alter Functional Properties of the Cardiac Ryanodine Receptor

Two single-nucleotide polymorphisms in the type 2 ryanodine receptor (RyR2) leading to the nonsynonymous amino acid replacements G1885E and G1886S are associated with arrhythmogenic right ventricular cardiomyopathy in patients who are carrying both of the corresponding RyR2 alleles. The functional properties of HEK293 cell lines isogenically expressing RyR2 mutants associated with arrhythmogenic right ventricular cardiomyopathy, RyR2-G1885E, RyR2-G1886S, RyR2-G1886D (mimicking a constitutively phosphorylated Ser1886), and the double mutant RyR2-G1885E/G1886S were investigated by analyzing the intracellular Ca2+ release activity resulting from store-overload-induced calcium release. The substitution of serine for Gly1886 caused a significant increase in the cellular Ca2+ oscillation activity compared with RyR2 wild-type-expressing HEK293 cells. It was even more pronounced if glycine 1885 or 1886 was replaced by the acidic amino acids glutamate (G1885E) or aspartate (G1886D). Surprisingly, when both substitutions were introduced in the same RyR2 subunit (RyR2-G1885E/G1886S), the store-overload-induced calcium release activity was nearly completely abolished, although the Ca2+ loading of the intracellular stores was markedly enhanced, and the channel still displayed substantial Ca2+ release on stimulation by 5 mM caffeine. These results suggest that the adjacent glycines 1885 and 1886, located in the divergent region 3, are critical for the function and regulation of RyR2

Direct Measurement of the Top Quark Mass at D0

We determine the top quark mass m_t using t-tbar pairs produced in the D0 detector by \sqrt{s} = 1.8 TeV p-pbar collisions in a 125 pb^-1 exposure at the Fermilab Tevatron. We make a two constraint fit to m_t in t-tbar -> b W^+bbar W^- final states with one W boson decaying to q-qbar and the other to e-nu or mu-nu. Likelihood fits to the data yield m_t(l+jets) = 173.3 +- 5.6 (stat) +- 5.5 (syst) GeV/c^2. When this result is combined with an analysis of events in which both W bosons decay into leptons, we obtain m_t = 172.1 +- 5.2 (stat) +- 4.9 (syst) GeV/c^2. An alternate analysis, using three constraint fits to fixed top quark masses, gives m_t(l+jets) = 176.0 +- 7.9 (stat) +- 4.8 (syst) GeV/C^2, consistent with the above result. Studies of kinematic distributions of the top quark candidates are also presented.Comment: 43 pages, 53 figures, 33 tables. RevTeX. Submitted to Phys. Rev.

Search for W~1Z~2\widetilde{W}_1\widetilde{Z}_2 Production via Trilepton Final States in ppˉp\bar{p} collisions at s=1.8\sqrt{s}=1.8 TeV

We have searched for associated production of the lightest chargino, $\widetilde{W}_1$, and next-to-lightest neutralino, $\widetilde{Z}_2$, of the Minimal Supersymmetric Standard Model in $p\bar{p}$ collisions at \mbox{$\sqrt{s}$ = 1.8 TeV} using the \D0 detector at the Fermilab Tevatron collider. Data corresponding to an integrated luminosity of 12.5$\pm 0.7$ \ipb were examined for events containing three isolated leptons. No evidence for $\widetilde{W}_1\widetilde{Z}_2$ pair production was found. Limits on $\sigma(\widetilde{W}_1\widetilde{Z}_2)$Br$(\widetilde{W}_1\to l\nu\widetilde{Z}_1)$Br$(\widetilde{Z}_2\to l\bar{l}\widetilde{Z}_1)$ are presented.Comment: 17 pages (13 + 1 page table + 3 pages figures). 3 PostScript figures will follow in a UUEncoded, gzip'd, tar file. Text in LaTex format. Submitted to Physical Review Letters. Replace comments - Had to resumbmit version with EPSF directive