A Cation-π Interaction in the Binding Site of the Glycine Receptor Is Mediated by a Phenylalanine Residue

Cys-loop receptor binding sites characteristically contain many aromatic amino acids. In nicotinic ACh and 5-HT3 receptors, a Trp residue forms a cation-{pi} interaction with the agonist, whereas in GABAA receptors, a Tyr performs this role. The glycine receptor binding site, however, contains predominantly Phe residues. Homology models suggest that two of these Phe side chains, Phe159 and Phe207, and possibly a third, Phe63, are positioned such that they could contribute to a cation-{pi} interaction with the primary amine of glycine. Here, we test this hypothesis by incorporation of a series of fluorinated Phe derivatives using unnatural amino acid mutagenesis. The data reveal a clear correlation between the glycine EC50 value and the cation-{pi} binding ability of the fluorinated Phe derivatives at position 159, but not at positions 207 or 63, indicating a single cation-{pi} interaction between glycine and Phe159. The data thus provide an anchor point for locating glycine in its binding site, and demonstrate for the first time a cation-{pi} interaction between Phe and a neurotransmitter

Delayed dispersal and the cost and benefits of different routes to independent breeding in a cooperative breeding bird

Why sexually mature individuals stay in groups as non-reproductive subordinates is central to the evolution of sociality and cooperative breeding. To understand such delayed dispersal, its costs and benefits need to be compared with those of permanently leaving to float through the population. However, comprehensive comparisons, especially regarding differences in future breeding opportunities, are rare. Moreover, extra-territorial prospecting by philopatric individuals has generally been ignored, even though the factors underlying this route to independent breeding may differ from those of strict philopatry or floating. We use a comprehensive predictive framework to explore how various costs, benefits and intrinsic, environmental and social factors explain philopatry, prospecting and floating in Seychelles warblers (Acrocephalus sechellensis). Floaters more likely obtained an independent breeding position before the next season than strictly philopatric individuals, but also suffered higher mortality. Prospecting yielded similar benefits to floating but lower mortality costs, suggesting that it is overall more beneficial than floating and strict philopatry. Whereas prospecting is probably individual-driven, though limited by resource availability, floating likely results from eviction by unrelated breeders. Such differences in proximate and ultimate factors underlying each route to independent breeding highlight the need for simultaneous consideration when studying the evolution of delayed dispersal

Consequences of sibling rivalry vary across life in a passerine bird

Many studies have assessed the costs of sibling rivalry in systems where offspring always have competitors, but conclusions about sibling rivalry in these species are restricted to interpreting the cost of changes in the relative level of competition and are often complicated by the expression of potentially costly rivalry related traits. Additionally, the majority of studies focus on early-life sibling rivalry, but the costs of competition can also affect later-life performance. We test a suite of hypothesized immediate (early-life body mass, telomere length, and survival) and delayed (adult reproductive potential and lifespan) costs of sibling rivalry for offspring of differing competitive ability in Seychelles warblers, where most offspring are raised singly and hence competitor success can be compared to a competition-free scenario. Compared to those raised alone, all competing nestlings had lower body mass and weaker competitors experienced reduced survival. However, the stronger competitors appeared to have longer adult breeding tenures and lifespan than those raised alone. We propose that comparisons with competition-free groups, as well as detailed fitness measures across entire lifetimes, are needed to understand the evolution of sibling rivalry and thus individual reproductive strategy in wild systems

Complex Scaled Spectrum Completeness for Coupled Channels

The Complex Scaling Method (CSM) provides scattering wave functions which regularize resonances and suggest a resolution of the identity in terms of such resonances, completed by the bound states and a smoothed continuum. But, in the case of inelastic scattering with many channels, the existence of such a resolution under complex scaling is still debated. Taking advantage of results obtained earlier for the two channel case, this paper proposes a representation in which the convergence of a resolution of the identity can be more easily tested. The representation is valid for any finite number of coupled channels for inelastic scattering without rearrangement.Comment: Latex file, 13 pages, 4 eps-figure

Experimentally induced antipredator responses are mediated by social and environmental factors

Nest predation is a common cause of reproductive failure for many bird species, and various antipredator defense behaviors have evolved to reduce the risk of nest predation. However, trade-offs between current reproductive duties and future reproduction often limit the parent’s ability to respond to nest predation risk. Individual responses to experimentally increased nest predation risk can give insights into these trade-offs. Here, we investigate whether social and ecological factors affect individual responses to predation risk by experimentally manipulating the risk of nest predation using taxidermic mounts in the cooperative breeding Seychelles warbler (Acrocephalus sechellensis). Our results show that dominant females, but not males, alarm called more often when they confront a nest predator model alone than when they do so with a partner, and that individuals that confront a predator together attacked more than those that did so alone. Dominant males increased their antipredator defense by spending more time nest guarding after a presentation with a nest predator, compared with a nonpredator control, but no such effect was found for females, who did not increase the time spent incubating. In contrast to incubation by females, nest guarding responses by dominant males depended on the presence of other group members and food availability. These results suggest that while female investment in incubation is always high and not dependent on social and ecological conditions, males have a lower initial investment, which allows them to respond to sudden changes in nest predation risk

The impact of adverse childhood experiences on health service use across the life course using a retrospective cohort study

Objectives: The lifelong health impacts of adverse childhood experiences are increasingly being identified, including earlier and more frequent development of non-communicable disease. Our aim was to examine whether adverse childhood experiences are related to increased use of primary, emergency and in-patient care and at what ages such impact is apparent. Methods: Household surveys were undertaken in 2015 with 7414 adults resident in Wales and England using random probability stratified sampling (age range 18–69 years). Nine adverse childhood experiences (covering childhood abuse and household stressors) and three types of health care use in the last 12 months were assessed: number of general practice (GP) visits, emergency department (ED) attendances and nights spent in hospital. Results: Levels of use increased with increasing numbers of adverse childhood experiences experienced. Compared to those with no adverse childhood experiences, odds ( 95% CIs) of frequent GP use ( 6 visits), any ED attendance or any overnight hospital stay were 2.34 (1.88–2.92), 2.32 (1.90–2.83) and 2.67 (2.06–3.47) in those with 4 adverse childhood experiences. Differences were independent of socio-economic measures of deprivation and other demographics. Higher health care use in those with 4 adverse childhood experiences (compared with no adverse childhood experiences) was evident at 18–29 years of age and continued through to 50–59 years. Demographically adjusted means for ED attendance rose from 12.2% of 18-29 year olds with no adverse childhood experiences to 28.8% of those with 4 adverse childhood experiences. At 60–69 years, only overnight hospital stay was significant (9.8% vs. 25.0%). Conclusions: Along with the acute impacts of adverse childhood experiences on child health, a life course perspective provides a compelling case for investing in safe and nurturing childhoods. Disproportionate health expenditure in later life might be reduced through childhood interventions to prevent adverse childhood experiences

The effect of metallicity on the Cepheid distance scale and its implications for the Hubble constant (H0H_0) determination

Recent HST determinations of the expansion's rate of the Universe (the Hubble constant, H_0) assumed that the Cepheid Period-Luminosity relation at V and I are independent of metallicity (Freedman, et al., 1996, Saha et al., 1996, Tanvir et al., 1995). The three groups obtain different vales for H_0. We note that most of this discrepancy stems from the asumption (by both groups) that the Period-Luminosity relation is independent of metallicity. We come to this conclusion as a result of our study of the Period-Luminosity relation of 481 Cepheids with 3 millions two colour measurements in the Large Magellanic Cloud and the Small Magellanic Cloud obtained as a by-product of the EROS microlensing survey. We find that the derived interstellar absorption corrections are particularly sensitive to the metallicity and when our result is applied to recent estimates based on HST Cepheids observations it makes the low-H_0 values higher and the high-H_0 value lower, bringing those discrepant estimates into agrement around $H_0 \approx 70 km/s Mpc^{-1}$.Comment: 4 pages, Latex, with 2 .ps accepted for publication astronomy and astrophysics Letter

Removing the Microlensing Blending-Parallax Degeneracy Using Source Variability

Microlensing event MACHO 97-SMC-1 is one of the rare microlensing events for which the source is a variable star, simply because most variable stars are systematically eliminated from microlensing studies. Using observational data for this event, we show that the intrinsic variability of a microlensed star is a powerful tool to constrain the nature of the lens by breaking the degeneracy between the microlens parallax and the blended light. We also present a statistical test for discriminating the location of the lens based on the \chi^2 contours of the vector \Lambda, the inverse of the projected velocity. We find that while SMC self lensing is somewhat favored over halo lensing, neither location can be ruled out with good confidence.Comment: 15 text pages + 2 tables + 7 figures. Published in the Astrophysical Journa

Observational Limits on Machos in the Galactic Halo

We present final results from the first phase of the EROS search for gravitational microlensing of stars in the Magellanic Clouds by unseen deflectors (machos: MAssive Compact Halo Objects). The search is sensitive to events with time scales between 15 minutes and 200 days corresponding to deflector masses in the range 1.e-7 to a few solar masses. Two events were observed that are compatible with microlensing by objects of mass of about 0.1 Mo. By comparing the results with the expected number of events for various models of the Galaxy, we conclude that machos in the mass range [1.e-7, 0.02] Mo make up less than 20% (95% C.L.) of the Halo dark matter.Comment: 4 pages, 3 Postscript figures, to be published in Astronomy & Astrophysic

The EROS2 search for microlensing events towards the spiral arms: the complete seven season results

The EROS-2 project has been designed to search for microlensing events towards any dense stellar field. The densest parts of the Galactic spiral arms have been monitored to maximize the microlensing signal expected from the stars of the Galactic disk and bulge. 12.9 million stars have been monitored during 7 seasons towards 4 directions in the Galactic plane, away from the Galactic center. A total of 27 microlensing event candidates have been found. Estimates of the optical depths from the 22 best events are provided. A first order interpretation shows that simple Galactic models with a standard disk and an elongated bulge are in agreement with our observations. We find that the average microlensing optical depth towards the complete EROS-cataloged stars of the spiral arms is $\bar{\tau} =0.51\pm .13\times 10^{-6}$, a number that is stable when the selection criteria are moderately varied. As the EROS catalog is almost complete up to $I_C=18.5$, the optical depth estimated for the sub-sample of bright target stars with $I_C<18.5$ ($\bar{\tau}=0.39\pm >.11\times 10^{-6}$) is easier to interpret. The set of microlensing events that we have observed is consistent with a simple Galactic model. A more precise interpretation would require either a better knowledge of the distance distribution of the target stars, or a simulation based on a Galactic model. For this purpose, we define and discuss the concept of optical depth for a given catalog or for a limiting magnitude.Comment: 22 pages submitted to Astronomy & Astrophysic