Differential Actions of Ethanol and Trichloroethanol at Sites in the M3 and M4 Domains of the NMDA Receptor GluN2A (NR2A) Subunit

Background and purpose:  Alcohol produces its behavioural effects in part due to inhibition of N-methyl-d-aspartate (NMDA) receptors in the CNS. Previous studies have identified amino acid residues in membrane-associated domains 3 (M3) and 4 (M4) of the NMDA receptor that influence ethanol sensitivity. In addition, in other alcohol-sensitive ion channels, sedative-hypnotic agents have in some cases been shown to act at sites distinct from the sites of ethanol action. In this study, we compared the influence of mutations at these sites on sensitivity to ethanol and trichloroethanol, a sedative-hypnotic agent that is a structural analogue of ethanol. Experimental approach:  We constructed panels of mutants at ethanol-sensitive positions in the GluN2A (NR2A) NMDA receptor subunit and transiently expressed these mutants in human embryonic kidney 293 cells. We used whole-cell patch-clamp recording to assess the actions of ethanol and trichloroethanol in these mutant NMDA receptors. Key results:  Ethanol sensitivity of mutants at GluN2A(Ala825) was not correlated with any physicochemical measures tested. Trichloroethanol sensitivity was altered in two of three ethanol-insensitive mutant GluN2A subunits: GluN2A(Phe637Trp) in M3 and GluN2A(Ala825Trp) in M4, but not GluN2A(Met823Trp). Trichloroethanol sensitivity decreased with increasing molecular volume at Phe637 or increasing hydrophobicity at Ala825 and was correlated with ethanol sensitivity at both sites. Conclusions and implications:  Evidence obtained to date is consistent with a role of GluN2A(Ala825) as a modulatory site for ethanol and trichloroethanol sensitivity, but not as a binding site. Trichloroethanol appears to inhibit the NMDA receptor in a manner similar, but not identical to, that of ethanol

Consumer mobility predicts impacts of herbivory across an environmental stress gradient

Author Posting. © Ecological Society of America, 2019. This article is posted here by permission of Ecological Society of America for personal use, not for redistribution. The definitive version was published in Ecology, (2019): e02910, doi:10.1002/ecy.2910.Environmental stress impedes predation and herbivory by limiting the ability of animals to search for and consume prey. We tested the contingency of this relationship on consumer traits and specifically hypothesized that herbivore mobility relative to the return time of limiting environmental stress would predict consumer effects. We examined how wave‐induced water motion affects marine communities via herbivory by highly mobile (fish) vs. slow‐moving (pencil urchin) consumers at two wave‐sheltered and two wave‐exposed rocky subtidal locations in the Galapagos Islands. The exposed locations experienced 99th percentile flow speeds that were 2–5 times greater than sheltered locations, with mean flow speeds >33 cm/s vs. <16 cm/s, 2–7 times higher standing macroalgal cover and 2–3 times lower cover of crustose coralline algae than the sheltered locations. As predicted by the environmental stress hypothesis (ESH), there was a negative relationship between mean flow speed and urchin abundance and herbivory rates on Ulva spp. algal feeding assays. In contrast, the biomass of surgeonfishes (Acanthuridae) and parrotfishes (Labridae: Scarinae) was positively correlated with mean flow speed. Ulva assays were consumed at equal rates by fish at exposed and sheltered locations, indicating continued herbivory even when flow speeds surpassed maximum reported swimming speeds at a rate of 1–2 times per minute. Modeled variation in fish species richness revealed minimal effects of diversity on herbivory rates at flow speeds <40 cm/s, when all species were capable of foraging, and above 120 cm/s, when no species could forage, while increasing diversity maximized herbivory rates at flow speeds of 40–120 cm/s. Two‐month herbivore exclusion experiments during warm and cool seasons revealed that macroalgal biomass was positively correlated with flow speed. Fish limited macroalgal development by 65–91% at one exposed location but not the second and by 70% at the two sheltered locations. In contrast, pencil urchins did not affect algal communities at either exposed location, but reduced macroalgae by 87% relative to controls at both sheltered locations. We propose an extension of the ESH that is contingent upon mobility to explain species‐specific changes in feeding rates and consumer effects on benthic communities across environmental gradients.This study was made possible through funding from the National Science Foundation (awards OCE‐1061475, OCE‐1450214, and OCE‐1623867) and the Galapagos Conservancy to JDW, and grants from the Rufford Foundation, the American Museum of Natural History, the Institute at Brown for Environment and Society, and the Bushnell Research and Education Fund to RWL. We are deeply grateful to Max Hirschfeld, Paul Tompkins, Etienne Rastoin, Inti Keith, Anaide Aued, Salome Buglass, Blake Hamilton, Fiona Beltram, Camila Lupi, Calvin Munson, and Maya Greenhill for assistance in the lab and in the field. Captain Nelson Ibarra, Captain Wilton Aguirre, and Captain Viko Rosero provided diving logistics aboard their boats. We also thank Arturo Izurieta, Marta Romolereaux, Heinke Jäger, and the Charles Darwin Research Station for field research support, and Danny Rueda, Jorge Carrion, Jenifer Suarez, and the Galapagos National Park for granting us authorization to carry out this investigation (research permit PC‐06–16). This publication is contribution number 2285 of the Charles Darwin Foundation for the Galapagos Islands

Functional Interactions of Alcohol-sensitive Sites in the \u3cem\u3eN\u3c/em\u3e-Methyl-d-aspartate Receptor M3 and M4 Domains

The N-methyl-d-aspartate receptor is an important mediator of the behavioral effects of ethanol in the central nervous system. Previous studies have demonstrated sites in the third and fourth membrane-associated (M) domains of the N-methyl-d-aspartate receptor NR2A subunit that influence alcohol sensitivity and ion channel gating. We investigated whether two of these sites, Phe-637 in M3 and Met-823 in M4, interactively regulate the ethanol sensitivity of the receptor by testing dual substitution mutants at these positions. A majority of the mutations decreased steady-state glutamate EC50 values and maximal steady-state to peak current ratios (Iss/Ip), whereas only two mutations altered peak glutamate EC50 values. Steady-state glutamate EC50 values were correlated with maximal glutamate Iss/Ip values, suggesting that changes in glutamate potency were attributable to changes in desensitization. In addition, there was a significant interaction between the substituents at positions 637 and 823 with respect to glutamate potency and desensitization. IC50 values for ethanol among the mutants varied over the approximate range 100–325 mm. The sites in M3 and M4 significantly interacted in regulating ethanol sensitivity, although this was apparently dependent upon the presence of methionine in position 823. Molecular dynamics simulations of the NR2A subunit revealed possible binding sites for ethanol near both positions in the M domains. Consistent with this finding, the sum of the molecular volumes of the substituents at the two positions was not correlated with ethanol IC50 values. Thus, there is a functional interaction between Phe-637 and Met-823 with respect to glutamate potency, desensitization, and ethanol sensitivity, but the two positions do not appear to form a unitary site of alcohol action

Marine reserves in The Bahamas and Ecuador : a scientific and socioeconomic perspective

Marine reserves are known to directly replenish overfished species. However, the community-wide effects of reserves are less clear. I examined the community of coralreef fishes in a large, fully protected marine reserve in The Bahamas: the Exuma Cays Land and Sea Park. Visual-transect surveys provided estimates and comparisons of the density and size of all fishes on reefs located both inside and outside the reserve (n = 5 reefs each). Apex predators were larger and more abundant inside the reserve, resulting in much greater biomass there. Mid-trophic-level species had somewhat higher biomass outside of the reserve, where abundance of large predators was lower. Low-trophic-level species showed trends of higher biomass in the reserve. Although the community-wide effects of the reserve are complex, this general pattern is consistent with the existence of a trophic cascade through strong top-down effects of apex predators. I also considered how subsistence-level fishing communities interact with protected marine life in a marine reserve in Ecuador: the Machalilla National Park. I examined the conflicting interests of park protection, fishing, and tourism. By analyzing these three categories, I summarized the needs and values of each group and how they interacted with each other and the environment

Influence of radiative damping on the optical-frequency susceptibility

Motivated by recent discussions concerning the manner in which damping appears in the electric polarizability, we show that (a) there is a dependence of the nonresonant contribution on the damping and that (b) the damping enters according to the "opposite sign prescription." We also discuss the related question of how the damping rates in the polarizability are related to energy-level decay rates

Centerscope

Centerscope, formerly Scope, was published by the Boston University Medical Center "to communicate the concern of the Medical Center for the development and maintenance of improved health care in contemporary society.

The C4 Clustering Algorithm: Clusters of Galaxies in the Sloan Digital Sky Survey

We present the "C4 Cluster Catalog", a new sample of 748 clusters of galaxies identified in the spectroscopic sample of the Second Data Release (DR2) of the Sloan Digital Sky Survey (SDSS). The C4 cluster--finding algorithm identifies clusters as overdensities in a seven-dimensional position and color space, thus minimizing projection effects which plagued previous optical clusters selection. The present C4 catalog covers ~2600 square degrees of sky with groups containing 10 members to massive clusters having over 200 cluster members with redshifts. We provide cluster properties like sky location, mean redshift, galaxy membership, summed r--band optical luminosity (L_r), velocity dispersion, and measures of substructure. We use new mock galaxy catalogs to investigate the sensitivity to the various algorithm parameters, as well as to quantify purity and completeness. These mock catalogs indicate that the C4 catalog is ~90% complete and 95% pure above M_200 = 1x10^14 solar masses and within 0.03 <=z <= 0.12. The C4 algorithm finds 98% of X-ray identified clusters and 90% of Abell clusters within 0.03 <= z <= 0.12. We show that the L_r of a cluster is a more robust estimator of the halo mass (M_200) than the line-of-sight velocity dispersion or the richness of the cluster. L_r. The final SDSS data will provide ~2500 C4 clusters and will represent one of the largest and most homogeneous samples of local clusters.Comment: 32 pages of figures and text accepted in AJ. Electronic version with additional tables, links, and figures is available at http://www.ctio.noao.edu/~chrism/c

A Survey of z>5.7 Quasars in the Sloan Digital Sky Survey II: Discovery of Three Additional Quasars at z>6

We present the discovery of three new quasars at z>6 in 1300 deg^2 of SDSS imaging data, J114816.64+525150.3 (z=6.43), J104845.05+463718.3 (z=6.23) and J163033.90+401209.6 (z=6.05). The first two objects have weak Ly alpha emission lines; their redshifts are determined from the positions of the Lyman break. They are only accurate to 0.05 and could be affected by the presence of broad absorption line systems. The last object has a Ly alpha strength more typical of lower redshift quasars. Based on a sample of six quasars at z>5.7 that cover 2870 deg^2 presented in this paper and in Paper I, we estimate the comoving density of luminous quasars at z 6 and M_{1450} < -26.8 to be (8 +/- 3)x10^{-10} Mpc^{-3} (for H_0 = 50 km/s/Mpc, Omega = 1). HST imaging of two z>5.7 quasars and high-resolution ground-based images (seeing 0.4'') of three additional z>5.7 quasars show that none of them is gravitationally lensed. The luminosity distribution of the high-redshfit quasar sample suggests the bright end slope of the quasar luminosity function at z 6 is shallower than Psi L^{-3.5} (2-sigma), consistent with the absence of strongly lensed objects.Comment: AJ in press (Apr 2003), 26 pages, 9 figure