87 research outputs found

    Annexin-A5 assembled into two-dimensional arrays promotes cell membrane repair

    Get PDF
    Eukaryotic cells possess a universal repair machinery that ensures rapid resealing of plasma membrane disruptions. Before resealing, the torn membrane is submitted to considerable tension, which functions to expand the disruption. Here we show that annexin-A5 (AnxA5), a protein that self-assembles into two-dimensional (2D) arrays on membranes upon Ca2+ activation, promotes membrane repair. Compared with wild-type mouse perivascular cells, AnxA5-null cells exhibit a severe membrane repair defect. Membrane repair in AnxA5-null cells is rescued by addition of AnxA5, which binds exclusively to disrupted membrane areas. In contrast, an AnxA5 mutant that lacks the ability of forming 2D arrays is unable to promote membrane repair. We propose that AnxA5 participates in a previously unrecognized step of the membrane repair process: triggered by the local influx of Ca2+, AnxA5 proteins bind to torn membrane edges and form a 2D array, which prevents wound expansion and promotes membrane resealing

    Process Drivers, Inter-Model Spread, and the Path Forward: A Review of Amplified Arctic Warming

    Get PDF
    This is the final version. Available on open access from Frontiers Media via the DOI in this recordArctic amplification (AA) is a coupled atmosphere-sea ice-ocean process. This understanding has evolved from the early concept of AA, as a consequence of snow-ice line progressions, through more than a century of research that has clarified the relevant processes and driving mechanisms of AA. The predictions made by early modeling studies, namely the fall/winter maximum, bottom-heavy structure, the prominence of surface albedo feedback, and the importance of stable stratification have withstood the scrutiny of multi-decadal observations and more complex models. Yet, the uncertainty in Arctic climate projections is larger than in any other region of the planet, making the assessment of high-impact, near-term regional changes difficult or impossible. Reducing this large spread in Arctic climate projections requires a quantitative process understanding. This manuscript aims to build such an understanding by synthesizing current knowledge of AA and to produce a set of recommendations to guide future research. It briefly reviews the history of AA science, summarizes observed Arctic changes, discusses modeling approaches and feedback diagnostics, and assesses the current understanding of the most relevant feedbacks to AA. These sections culminate in a conceptual model of the fundamental physical mechanisms causing AA and a collection of recommendations to accelerate progress towards reduced uncertainty in Arctic climate projections. Our conceptual model highlights the need to account for local feedback and remote process interactions within the context of the annual cycle to constrain projected AA. We recommend raising the priority of Arctic climate sensitivity research, improving the accuracy of Arctic surface energy budget observations, rethinking climate feedback definitions, coordinating new model experiments and intercomparisons, and further investigating the role of episodic variability in AA.NASANatural Sciences and Engineering Research Council of Canada (NSERC)US National Science foundationAlfred P. Sloan FoundationNatural Environment Research Council (NERC

    [11C]-l-Methionine positron emission tomography in the management of children and young adults with brain tumors

    Get PDF
    Only a few Methyl-[11C]-l-methionine (MET) positron emission tomography (PET) studies have focused on children and young adults with brain neoplasm. Due to radiation exposure, long scan acquisition time, and the need for sedation in young children MET-PET studies should be restricted to this group of patients when a decision for further therapy is not possible from routine diagnostic procedures alone, e.g., structural imaging. We investigated the diagnostic accuracy of MET-PET for the differentiation between tumorous and non-tumorous lesions in this group of patients. Forty eight MET-PET scans from 39 patients aged from 2 to 21 years (mean 15 ± 5.0 years) were analyzed. The MET tumor-uptake relative to a corresponding control region was calculated. A receiver operating characteristic (ROC) was performed to determine the MET-uptake value that best distinguishes tumorous from non-tumorous brain lesions. A differentiation between tumorous (n = 39) and non-tumorous brain lesions (n = 9) was possible at a threshold of 1.48 of relative MET-uptake with a sensitivity of 83% and a specificity of 92%, respectively. A differentiation between high grade malignant lesions (mean MET-uptake = 2.00 ± 0.46) and low grade tumors (mean MET-uptake = 1.84 ± 0.31) was not possible. There was a significant difference in MET-uptake between the histologically homogeneous subgroups of astrocytoma WHO grade II and anaplastic astrocytoma WHO grade III (P = 0.02). MET-PET might be a useful tool to differentiate tumorous from non-tumorous lesions in children and young adults when a decision for further therapy is difficult or impossible from routine structural imaging procedures alone

    DCE-MRI perfusion and permeability parameters as predictors of tumor response to CCRT in patients with locally advanced NSCLC

    Get PDF
    In this prospective study, 36 patients with stage III non-small cell lung cancers (NSCLC), who underwent dynamic contrast-enhanced MRI (DCE-MRI) before concurrent chemo-radiotherapy (CCRT) were enrolled. Pharmacokinetic analysis was carried out after non-rigid motion registration. The perfusion parameters including Blood Flow (BF), Blood Volume (BV), Mean Transit Time (MTT) and permeability parameters including endothelial transfer constant (Ktrans), reflux rate (Kep), fractional extravascular extracellular space volume (Ve), fractional plasma volume (Vp) were calculated, and their relationship with tumor regression was evaluated. The value of these parameters on predicting responders were calculated by receiver operating characteristic (ROC) curve. Multivariate logistic regression analysis was conducted to find the independent variables. Tumor regression rate is negatively correlated with V e and its standard variation V e-SD and positively correlated with K trans and Kep. Significant differences between responders and non-responders existed in Ktrans, Kep, Ve, Ve-SD, MTT, BV-SD and MTT-SD (P < 0.05). ROC indicated that Ve < 0.24 gave the largest area under curve of 0.865 to predict responders. Multivariate logistic regression analysis also showed Ve was a significant predictor. Baseline perfusion and permeability parameters calculated from DCE-MRI were seen to be a viable tool for predicting the early treatment response after CCRT of NSCLC. © 2016 The Author(s)

    Ballistic transport and boundary resistances in inhomogeneous quantum spin chains

    Get PDF
    Transport phenomena are central to physics, and transport in the many-body and fully-quantum regime is attracting an increasing amount of attention. It has been recently revealed that some quantum spin chains support ballistic transport of excitations at all energies. However, when joining two semi-infinite ballistic parts, such as the XX and XXZ spin-1/2 models, our understanding suddenly becomes less established. Employing a matrix-product-state ansatz of the wavefunction, we study the relaxation dynamics in this latter case. Here we show that it takes place inside a light cone, within which two qualitatively different regions coexist: an inner one with a strong tendency towards thermalization, and an outer one supporting ballistic transport. We comment on the possibility that even at infinite time the system supports stationary currents and displays a non-zero Kapitza boundary resistance. Our study paves the way to the analysis of the interplay between transport, integrability, and local defects

    Mass balance of the Greenland and Antarctic ice sheets from 1992 to 2020

    Get PDF
    Ice losses from the Greenland and Antarctic ice sheets have accelerated since the 1990s, accounting for a significant increase in the global mean sea level. Here, we present a new 29-year record of ice sheet mass balance from 1992 to 2020 from the Ice Sheet Mass Balance Inter-comparison Exercise (IMBIE). We compare and combine 50 independent estimates of ice sheet mass balance derived from satellite observations of temporal changes in ice sheet flow, in ice sheet volume, and in Earth's gravity field. Between 1992 and 2020, the ice sheets contributed 21.0±1.9g€¯mm to global mean sea level, with the rate of mass loss rising from 105g€¯Gtg€¯yr-1 between 1992 and 1996 to 372g€¯Gtg€¯yr-1 between 2016 and 2020. In Greenland, the rate of mass loss is 169±9g€¯Gtg€¯yr-1 between 1992 and 2020, but there are large inter-annual variations in mass balance, with mass loss ranging from 86g€¯Gtg€¯yr-1 in 2017 to 444g€¯Gtg€¯yr-1 in 2019 due to large variability in surface mass balance. In Antarctica, ice losses continue to be dominated by mass loss from West Antarctica (82±9g€¯Gtg€¯yr-1) and, to a lesser extent, from the Antarctic Peninsula (13±5g€¯Gtg€¯yr-1). East Antarctica remains close to a state of balance, with a small gain of 3±15g€¯Gtg€¯yr-1, but is the most uncertain component of Antarctica's mass balance. The dataset is publicly available at 10.5285/77B64C55-7166-4A06-9DEF-2E400398E452 (IMBIE Team, 2021)

    Greenland ice sheet surface mass loss: recent developments in observation and modeling

    Get PDF
    Surface processes currently dominate Greenland ice sheet (GrIS) mass loss. We review recent developments in the observation and modelling of GrIS surface mass balance (SMB), published after the July 2012 deadline for the Fifth Assessment Report of the Intergovernmental Panel on Climate Change (IPCC AR5). Since IPCC AR5 our understanding of GrIS SMB has further improved, but new observational and model studies have also revealed that temporal and spatial variability of many processes are still poorly quantified and understood, e.g. bio-albedo, the formation of ice lenses and their impact on lateral meltwater transport, heterogeneous vertical meltwater transport (‘piping’), the impact of atmospheric circulation changes and mixed-phase clouds on the surface energy balance and the magnitude of turbulent heat exchange over rough ice surfaces. As a result, these processes are only schematically or not at all included in models that are currently used to assess and predict future GrIS surface mass loss

    Predicting climate change using response theory: global averages and spatial patterns

    Get PDF
    The provision of accurate methods for predicting the climate response to anthropogenic and natural forcings is a key contemporary scientific challenge. Using a simplified and efficient open-source general circulation model of the atmosphere featuring O(105105) degrees of freedom, we show how it is possible to approach such a problem using nonequilibrium statistical mechanics. Response theory allows one to practically compute the time-dependent measure supported on the pullback attractor of the climate system, whose dynamics is non-autonomous as a result of time-dependent forcings. We propose a simple yet efficient method for predicting—at any lead time and in an ensemble sense—the change in climate properties resulting from increase in the concentration of CO22 using test perturbation model runs. We assess strengths and limitations of the response theory in predicting the changes in the globally averaged values of surface temperature and of the yearly total precipitation, as well as in their spatial patterns. The quality of the predictions obtained for the surface temperature fields is rather good, while in the case of precipitation a good skill is observed only for the global average. We also show how it is possible to define accurately concepts like the inertia of the climate system or to predict when climate change is detectable given a scenario of forcing. Our analysis can be extended for dealing with more complex portfolios of forcings and can be adapted to treat, in principle, any climate observable. Our conclusion is that climate change is indeed a problem that can be effectively seen through a statistical mechanical lens, and that there is great potential for optimizing the current coordinated modelling exercises run for the preparation of the subsequent reports of the Intergovernmental Panel for Climate Change

    Microsatellite Support for Active Inbreeding in a Cichlid Fish

    Get PDF
    In wild animal populations, the degree of inbreeding differs between species and within species between populations. Because mating with kin often results in inbreeding depression, observed inbreeding is usually regarded to be caused by limited outbreeding opportunities due to demographic factors like small population size or population substructuring. However, theory predicts inclusive benefits from mating with kin, and thus part of the observed variation in inbreeding might be due to active inbreeding preferences. Although some recent studies indeed report kin mating preferences, the evidence is still highly ambiguous. Here, we investigate inbreeding in a natural population of the West African cichlid fish Pelvicachromis taeniatus which showed clear kin mating preferences in standardized laboratory experiments but no inbreeding depression. The presented microsatellite analysis reveals that the natural population has, in comparison to two reference populations, a reduced allelic diversity (A = 3) resulting in a low heterozygosity (Ho = 0.167) pointing to a highly inbred population. Furthermore, we found a significant heterozygote deficit not only at population (Fis = 0.116) but also at subpopulation level (Fis = 0.081) suggesting that inbreeding is not only a by-product of population substructuring but possibly a consequence of behavioral kin preferences
    • …
    corecore