The stoichiometry of P2X2/6 receptor heteromers depends on relative subunit expression levels

Fast synaptic transmission involves the operation of ionotropic receptors, which are often composed of at least two types of subunit. We have developed a method, based on atomic force microscopy imaging to determine the stoichiometry and subunit arrangement within ionotropic receptors. We showed recently that the P2X(2) receptor for ATP is expressed as a trimer but that the P2X(6) subunit is unable to oligomerize. In this study we addressed the subunit stoichiometry of heteromers containing both P2X(2) and P2X(6) subunits. We transfected tsA 201 cells with both P2X(2) and P2X(6) subunits, bearing different epitope tags. We manipulated the transfection conditions so that either P2X(2) or P2X(6) was the predominant subunit expressed. By atomic force microscopy imaging of isolated receptors decorated with antiepitope antibodies, we demonstrate that when expression of the P2X(2) subunit predominates, the receptors contain primarily 2 x P2X(2) subunits and 1 x P2X(6) subunit. In contrast, when the P2X(6) subunit predominates, the subunit stoichiometry of the receptors is reversed. Our results show that the composition of P2X receptor heteromers is plastic and dependent on the relative subunit expression levels. We suggest that this property of receptor assembly might introduce an additional layer of subtlety into P2X receptor signaling

Ecological theory predicts ecosystem stressor interactions in freshwater communities, but highlights the strengths and weaknesses of the additive null model

Understanding and predicting how multiple co-occurring environmental stressors combine to affect biodiversity and ecosystem services is an on-going grand challenge for ecology. So far progress has been made through accumulating large numbers of smaller-scale individual studies that are then investigated by meta-analyses to look for general patterns. In particular there has been an interest in checking for so-called ecological surprises where stressors interact in a synergistic manner. Recent reviews suggest that such synergisms do not dominate, but few other generalities have emerged. This lack of general prediction and understanding may be due in part to a dearth of ecological theory that can generate clear hypotheses and predictions to tested against empirical data. Here we close this gap by analysing food web models based upon classical ecological theory and comparing their predictions to a large (546 interactions) dataset for the effects of pairs of stressors on freshwater communities, using trophic- and population-level metrics of abundance, density, and biomass as responses. We find excellent overall agreement between the stochastic version of our models and the experimental data, and both conclude additive stressor interactions are the most frequent, but that meta-analyses report antagonistic summary interaction classes. Additionally, we show that the statistical tests used to classify the interactions are very sensitive to sampling variation. It is therefore likely that current weak sampling and low sample sizes are masking many non-additive stressor interactions, which our theory predicts to dominate when sampling variation is removed. This leads us to suspect ecological surprises may be more common than currently reported. Our results highlight the value of developing theory in tandem with empirical tests, and the need to examine the robustness of statistical machinery, especially the widely-used null models, before we can draw strong conclusions about how environmental drivers combine

Feasibility and systems definition study for Microwave Multi-Application Payload (MMAP)

Work completed on three Shuttle/Spacelab experiments is examined: the Adaptive Multibeam Phased Array Antenna (AMPA) Experiment, Electromagnetic Environment Experiment (EEE) and Millimeter Wave Communications Experiment (MWCE). Results included the definition of operating modes, sequence of operation, radii of operation about several ground stations, signal format, foot prints of typical orbits and preliminary definition of ground and user terminals. Conceptual hardware designs, Spacelab interfaces, data handling methods, experiment testing and verification studies were included. The MWCE-MOD I was defined conceptually for a steerable high gain antenna

A tight binding model for water

We demonstrate for the first time a tight binding model for water incorporating polarizable anions. A novel aspect is that we adopt a "ground up" approach in that properties of the monomer and dimer only are fitted. Subsequently we make predictions of the structure and properties of hexamer clusters, ice-XI and liquid water. A particular feature, missing in current tight binding and semiempirical hamiltonians, is that we reproduce the almost two-fold increase in molecular dipole moment as clusters are built up towards the limit of bulk liquid. We concentrate on properties of liquid water which are very well rendered in comparison with experiment and published density functional calculations. Finally we comment on the question of the contrasting densities of water and ice which is central to an understanding of the subtleties of the hydrogen bond

Growing Multiconfigurational Potential Energy Surfaces with Applications to X+H2 (X=C,N,O) Reactions

A previously developed method, based on a Shepard interpolation procedure to automatically construct a quantum mechanical potential energy surface (PES), is extended to the construction of multiple potential energy surfaces using multiconfigurational wave functions. These calculations are accomplished with the interface of the PES-building program, GROW, and the GAMESS suite of electronic structure programs. The efficient computation of multiconfigurational self-consistent field surfaces is illustrated with the C+H2, N+H2, and O+H2reactions

A multicentre, prospective, randomised, blinded clinical trial to compare some perioperative effects of buprenorphine or butorphanol premedication before equine elective general anaesthesia and surgery

REASONS FOR PERFORMING STUDY: Buprenorphine, a μ‐agonist opioid, has recently been licensed for equine use, but butorphanol, a κ‐agonist opioid, is more commonly used in horses. The effect of the 2 opioids has not previously been compared in a large clinical study. OBJECTIVES: To compare post operative analgesia and physiological variables in horses undergoing elective surgery following premedication with either buprenorphine or butorphanol in a conventional clinical setting. STUDY DESIGN: Multicentre, prospective, randomised, blinded clinical investigation. METHODS: Eighty‐nine healthy horses admitted for elective surgery to one of 6 UK equine veterinary clinics were premedicated with acepromazine, a nonsteroidal anti‐inflammatory drug, and romifidine followed by intravenous (i.v.) buprenorphine or butorphanol. Anaesthesia was induced with diazepam/ketamine and maintained with isoflurane in oxygen. A range of surgical procedures were performed and supplementary anaesthetic agents given as required. Physiological variables were monitored during anaesthesia and pain, ataxia, sedation and vital function were assessed post operatively. Data were analysed using t‐tests, ANOVA, Mann–Whitney U‐test and Chi‐squared test as appropriate and P<0.05 was regarded as significant, except for multiple comparisons, when P<0.01 was used. RESULTS: Surgery was carried out successfully in all cases and no mortality or serious morbidity occurred. Physiological variables remained within normal limits and all horses recovered successfully, most standing within 1 h of ceasing anaesthesia. There were no significant differences between groups in any variable except post operative pain when scores (simple descriptive scale) between 3 and 6 h were significantly lower after buprenorphine than after butorphanol. CONCLUSIONS: Horses experienced less post operative pain after buprenorphine than after butorphanol premedication. Compared with butorphanol, buprenorphine did not cause any different effects on vital function

State-to-State Differential and Relative Integral Cross Sections for Rotationally Inelastic Scattering of H2O by Hydrogen

State-to-state differential cross sections (DCSs) for rotationally inelastic scattering of H2O by H2 have been measured at 71.2 meV (574 cm-1) and 44.8 meV (361 cm-1) collision energy using crossed molecular beams combined with velocity map imaging. A molecular beam containing variable compositions of the (J = 0, 1, 2) rotational states of hydrogen collides with a molecular beam of argon seeded with water vapor that is cooled by supersonic expansion to its lowest para or ortho rotational levels (JKaKc= 000 and 101, respectively). Angular speed distributions of fully specified rotationally excited final states are obtained using velocity map imaging. Relative integral cross sections are obtained by integrating the DCSs taken with the same experimental conditions. Experimental state-specific DCSs are compared with predictions from fully quantum scattering calculations on the most complete H2O-H2 potential energy surface. Comparison of relative total cross sections and state-specific DCSs show excellent agreement with theory in almost all detailsComment: 46 page

Hypoxia in the northern Gulf of Mexico: Does the science support the Plan to Reduce, Mitigate, and Control Hypoxia?

We update and reevaluate the scientific information on the distribution, history, and causes of continental shelf hypoxia that supports the 2001 Action Plan for Reducing, Mitigating, and Controlling Hypoxia in the Northern Gulf of Mexico (Mississippi River/Gulf of Mexico Watershed Nutrient Task Force 2001), incorporating data, publications, and research results produced since the 1999 integrated assessment. The metric of mid-summer hypoxic area on the Louisiana-Texas shelf is an adequate and suitable measure for continued efforts to reduce nutrients loads from the Mississippi River and hypoxia in the northern Gulf of Mexico as outlined in the Action Plan. More frequent measurements of simple metrics (e.g., area and volume) from late spring through late summer would ensure that the metric is representative of the system in any given year and useful in a public discourse of conditions and causes. The long-term data on hypoxia, sources of nutrients, associated biological parameters, and paleoindicators continue to verify and strengthen the relationship between the nitrate-nitrogen load of the Mississippi River, the extent of hypoxia, and changes in the coastal ecosystem (eutrophication and worsening hypoxia). Multiple lines of evidence, some of them representing independent data sources, are consistent with the big picture pattern of increased eutrophication as a result of long-term nutrient increases that result in excess carbon production and accumulation and, ultimately, bottom water hypoxia. The additional findings arising since 1999 strengthen the science supporting the Action Plan that focuses on reducing nutrient loads, primarily nitrogen, through multiple actions to reduce the size of the hypoxic zone in the northern Gulf of Mexico

Spatial complementarity and the coexistence of species

Coexistence of apparently similar species remains an enduring paradox in ecology. Spatial structure has been predicted to enable coexistence even when population-level models predict competitive exclusion if it causes each species to limit its own population more than that of its competitor. Nevertheless, existing hypotheses conflict with regard to whether clustering favours or precludes coexistence. The spatial segregation hypothesis predicts that in clustered populations the frequency of intra-specific interactions will be increased, causing each species to be self-limiting. Alternatively, individuals of the same species might compete over greater distances, known as heteromyopia, breaking down clusters and opening space for a second species to invade. In this study we create an individual-based model in homogeneous two-dimensional space for two putative sessile species differing only in their demographic rates and the range and strength of their competitive interactions. We fully characterise the parameter space within which coexistence occurs beyond population-level predictions, thereby revealing a region of coexistence generated by a previously-unrecognised process which we term the triadic mechanism. Here coexistence occurs due to the ability of a second generation of offspring of the rarer species to escape competition from their ancestors. We diagnose the conditions under which each of three spatial coexistence mechanisms operates and their characteristic spatial signatures. Deriving insights from a novel metric — ecological pressure — we demonstrate that coexistence is not solely determined by features of the numerically-dominant species. This results in a common framework for predicting, given any pair of species and knowledge of the relevant parameters, whether they will coexist, the mechanism by which they will do so, and the resultant spatial pattern of the community. Spatial coexistence arises from complementary combinations of traits in each species rather than solely through self-limitation