Structure of the Vacuolar H⁺-ATPase Rotary Motor Reveals New Mechanistic Insights

Vacuolar H+-ATPases are multisubunit complexes that operate with rotary mechanics and are essential for membrane proton transport throughout eukaryotes. Here we report a ∼1 nm resolution reconstruction of a V-ATPase in a different conformational state from that previously reported for a lower-resolution yeast model. The stator network of the V-ATPase (and by implication that of other rotary ATPases) does not change conformation in different catalytic states, and hence must be relatively rigid. We also demonstrate that a conserved bearing in the catalytic domain is electrostatic, contributing to the extraordinarily high efficiency of rotary ATPases. Analysis of the rotor axle/membrane pump interface suggests how rotary ATPases accommodate different c ring stoichiometries while maintaining high efficiency. The model provides evidence for a half channel in the proton pump, supporting theoretical models of ion translocation. Our refined model therefore provides new insights into the structure and mechanics of the V-ATPases

Past rapid warmings as a constraint on greenhouse-gas climate feedbacks

There are large uncertainties in the estimation of greenhouse-gas climate feedback. Recent observations do not provide strong constraints because they are short and complicated by human interventions, while model-based estimates differ considerably. Rapid climate changes during the last glacial period (Dansgaard-Oeschger events), observed near-globally, were comparable in both rate and magnitude to current and projected 21st century climate warming and therefore provide a relevant constraint on feedback strength. Here we use these events to quantify the centennial-scale feedback strength of CO2, CH4 and N2O by relating global mean temperature changes, simulated by an appropriately forced low-resolution climate model, to the radiative forcing of these greenhouse gases derived from their concentration changes in ice-core records. We derive feedback estimates (expressed as dimensionless gain) of 0.14 ± 0.04 for CO2, 0.10 ± 0.02 for CH4, and 0.09 ± 0.03 for N2O. This indicates that much lower or higher estimates of gains, particularly some previously published values for CO2, are unrealistic

Fluid and Diffusion Limits for Bike Sharing Systems

Bike sharing systems have rapidly developed around the world, and they are served as a promising strategy to improve urban traffic congestion and to decrease polluting gas emissions. So far performance analysis of bike sharing systems always exists many difficulties and challenges under some more general factors. In this paper, a more general large-scale bike sharing system is discussed by means of heavy traffic approximation of multiclass closed queueing networks with non-exponential factors. Based on this, the fluid scaled equations and the diffusion scaled equations are established by means of the numbers of bikes both at the stations and on the roads, respectively. Furthermore, the scaling processes for the numbers of bikes both at the stations and on the roads are proved to converge in distribution to a semimartingale reflecting Brownian motion (SRBM) in a $N^{2}$-dimensional box, and also the fluid and diffusion limit theorems are obtained. Furthermore, performance analysis of the bike sharing system is provided. Thus the results and methodology of this paper provide new highlight in the study of more general large-scale bike sharing systems.Comment: 34 pages, 1 figure

Subunit positioning and stator filament stiffness in regulation and power transmission in the V1 motor of the manduca sexta V-ATpase

The vacuolar H(+)-ATPase (V-ATPase) is an ATP-driven proton pump essential to the function of eukaryotic cells. Its cytoplasmic V1 domain is an ATPase, normally coupled to membrane-bound proton pump Vo via a rotary mechanism. How these asymmetric motors are coupled remains poorly understood. Low energy status can trigger release of V1 from the membrane and curtail ATP hydrolysis. To investigate the molecular basis for these processes, we have carried out cryo-electron microscopy three-dimensional reconstruction of deactivated V1 from Manduca sexta. In the resulting model, three peripheral stalks that are parts of the mechanical stator of the V-ATPase are clearly resolved as unsupported filaments in the same conformations as in the holoenzyme. They are likely therefore to have inherent stiffness consistent with a role as flexible rods in buffering elastic power transmission between the domains of the V-ATPase. Inactivated V1 adopted a homogeneous resting state with one open active site adjacent to the stator filament normally linked to the H subunit. Although present at 1:1 stoichiometry with V1, both recombinant subunit C reconstituted with V1 and its endogenous subunit H were poorly resolved in three-dimensional reconstructions, suggesting structural heterogeneity in the region at the base of V1 that could indicate positional variability. If the position of H can vary, existing mechanistic models of deactivation in which it binds to and locks the axle of the V-ATPase rotary motor would need to be re-evaluated

The China plant trait database version 2

Plant functional traits represent adaptive strategies to the environment, linked to biophysical and biogeochemical processes and ecosystem functioning. Compilations of trait data facilitate research in multiple fields from plant ecology through to land-surface modelling. Here we present version 2 of the China Plant Trait Database, which contains information on morphometric, physical, chemical, photosynthetic and hydraulic traits from 1529 unique species in 140 sites spanning a diversity of vegetation types. Version 2 has five improvements compared to the previous version: (1) new data from a 4-km elevation transect on the edge of Tibetan Plateau, including alpine vegetation types not sampled previously; (2) inclusion of traits related to hydraulic processes, including specific sapwood conductance, the area ratio of sapwood to leaf, wood density and turgor loss point; (3) inclusion of information on soil properties to complement the existing data on climate and vegetation (4) assessments and flagging the reliability of individual trait measurements; and (5) inclusion of standardized templates for systematical field sampling and measurements

Anointed or appointed? Father–daughter succession within the family business

With the focus on events and outcomes shaping most of the existing family business research on intra-family succession, the subtleties of the incumbent-successor relationship and the dynamic nature of succession as a process of becoming is somewhat neglected. In particular, we have limited understanding of how successor identities are constructed as legitimate between incumbent and successor during father-daughter succession. This article addresses this gap in understanding by exploring how the daughter successor engages in identity work with the father incumbent during the process of succession and the role of father-daughter gendered relations in shaping her successor identity. Using a two-stage research design strategy, we draw upon empirical evidence derived from 14 individual and joint semi-structured interviews to present a narrative analysis of five father-daughter dyads. In so doing, we unveil how the daughter’s successor identity was co-constructed as legitimate and how father-daughter gendered relations influenced this process. Although daughters rely on certain father-daughter relations (preparation, endorsement and osmotic credibility) for legitimacy, they also need to develop independently from their father in order to heighten their own visibility and establish credibility

An overview of ADSL Homed Nepenthes Honeypots In Western Australia

This paper outlines initial analysis from research in progress into ADSL homed Nepenthes honeypots. One of the Nepenthes honeypots prime objective in this research was the collection of malware for analysis and dissection. A further objective is the analysis of risks that are circulating within ISP networks in Western Australian. What differentiates Nepenthes from many traditional honeypot designs it that is has been engineered from a distributed network philosophy. The program allows distribution of results across a network of sensors and subsequent aggregation of malware statistics readily within a large network environment

Ethnic inequalities and pathways to care in psychosis in England: a systematic review and meta-analysis

© The Author(s). 2018Background: As part of a national programme to tackle ethnic inequalities, we conducted a systematic review and meta-analysis of research on ethnic inequalities in pathways to care for adults with psychosis living in England and/or Wales. Methods: Nine databases were searched from inception to 03.07.17 for previous systematic reviews, including forward and backward citation tracking and a PROSPERO search to identify ongoing reviews. We then carried forward relevant primary studies from included reviews (with the latest meta-analyses reporting on research up to 2012), supplemented by a search on 18.10.17 in MEDLINE, Embase, PsycINFO and CINAHL for primary studies between 2012 and 2017 that had not been covered by previous meta-analyses. Results: Forty studies, all conducted in England, were included for our updated meta-analyses on pathways to care. Relative to the White reference group, elevated rates of civil detentions were found for Black Caribbean (OR = 3.43, 95% CI = 2.68 to 4.40, n = 18), Black African (OR = 3.11, 95% CI = 2.40 to 4.02, n = 6), and South Asian patients (OR = 1.50, 95% CI 1.07 to 2.12, n = 10). Analyses of each Mental Health Act section revealed significantly higher rates for Black people under (civil) Section 2 (OR = 1.53, 95% CI = 1.11 to 2.11, n = 3). Rates in repeat admissions were significantly higher than in first admission for South Asian patients (between-group difference p < 0.01). Some ethnic groups had more police contact (Black African OR = 3.60, 95% CI = 2.15 to 6.05, n = 2; Black Caribbean OR = 2.64, 95% CI = 1.88 to 3.72, n = 8) and criminal justice system involvement (Black Caribbean OR = 2.76, 95% CI = 2.02 to 3.78, n = 5; Black African OR = 1.92, 95% CI = 1.32 to 2.78, n = 3). The White Other patients also showed greater police and criminal justice system involvement than White British patients (OR = 1.49, 95% CI = 1.03 to 2.15, n = 4). General practitioner involvement was less likely for Black than the White reference group. No significant variations over time were found across all the main outcomes. Conclusions: Our updated meta-analyses reveal persisting but not significantly worsening patterns of ethnic inequalities in pathways to psychiatric care, particularly affecting Black groups. This provides a comprehensive evidence base from which to inform policy and practice amidst a prospective Mental Health Act reform. Trial registration: CRD42017071663Peer reviewedFinal Published versio

Large-Theta(13) Perturbation Theory of Neutrino Oscillation for Long-Baseline Experiments

The Cervera et al. formula, the best known approximate formula of neutrino oscillation probability for long-baseline experiments, can be regarded as a second-order perturbative formula with small expansion parameter epsilon \equiv Delta m^2_{21} / Delta m^2_{31} \simeq 0.03 under the assumption s_{13} \simeq epsilon. If theta_{13} is large, as suggested by a candidate nu_{e} event at T2K as well as the recent global analyses, higher order corrections of s_{13} to the formula would be needed for better accuracy. We compute the corrections systematically by formulating a perturbative framework by taking theta_{13} as s_{13} \sim \sqrt{epsilon} \simeq 0.18, which guarantees its validity in a wide range of theta_{13} below the Chooz limit. We show on general ground that the correction terms must be of order epsilon^2. Yet, they nicely fill the mismatch between the approximate and the exact formulas at low energies and relatively long baselines. General theorems are derived which serve for better understanding of delta-dependence of the oscillation probability. Some interesting implications of the large theta_{13} hypothesis are discussed.Comment: Fig.2 added, 23 pages. Matches to the published versio

Live to cheat another day: bacterial dormancy facilitates the social exploitation of beta-lactamases

The breakdown of antibiotics by β-lactamases may be cooperative, since resistant cells can detoxify their environment and facilitate the growth of susceptible neighbours. However, previous studies of this phenomenon have used artificial bacterial vectors or engineered bacteria to increase the secretion of β-lactamases from cells. Here, we investigated whether a broad-spectrum β-lactamase gene carried by a naturally occurring plasmid (pCT) is cooperative under a range of conditions. In ordinary batch culture on solid media, there was little or no evidence that resistant bacteria could protect susceptible cells from ampicillin, although resistant colonies could locally detoxify this growth medium. However, when susceptible cells were inoculated at high densities, late-appearing phenotypically susceptible bacteria grew in the vicinity of resistant colonies. We infer that persisters, cells that have survived antibiotics by undergoing a period of dormancy, founded these satellite colonies. The number of persister colonies was positively correlated with the density of resistant colonies and increased as antibiotic concentrations decreased. We argue that detoxification can be cooperative under a limited range of conditions: if the toxins are bacteriostatic rather than bacteridical; or if susceptible cells invade communities after resistant bacteria; or if dormancy allows susceptible cells to avoid bactericides. Resistance and tolerance were previously thought to be independent solutions for surviving antibiotics. Here, we show that these are interacting strategies: the presence of bacteria adopting one solution can have substantial effects on the fitness of their neighbours