48 research outputs found

    Volume-regulated Cl- current: contributions of distinct Cl- channel and localized Ca2+ signals.

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    The swelling-activated chloride current (ICl,swell) is induced when a cell swells and plays a central role in maintaining cell volume in response to osmotic stress. The major contributor of ICl,swell is the volume regulated anion channel (VRAC). LRRC8A (SWELL1) was recently identified as an essential component of VRAC but the mechanisms of VRAC activation are still largely unknown; moreover, other Cl- channels, such as anoctamin 1 (ANO1) were also suggested to contribute to ICl,swell. In this present study, we investigated the roles of LRRC8A and ANO1 in activation of ICl,swell; we also explored the role of intracellular Ca2+ in ICl,swell activation. We used CRISPR/Cas9 gene editing approach, electrophysiology, live fluorescent imaging, selective pharmacology and other approaches to show that both LRRC8A and ANO1 can be activated by cell swelling in HEK293 cells. Yet, both channels contribute biophysically and pharmacologically distinct components to ICl,swell, with LRRC8A being the major component. Cell swelling induced oscillatory Ca2+ transients and these Ca2+ signals were required to activate both, the LRRC8A- and ANO1-dependent components of ICl,swell. Both ICl,swell components required localized rather than global Ca2+ for activation. Interestingly, while intracellular Ca2+ was necessary and sufficient to activate ANO1, it was necessary but not sufficient to activate LRRC8A-mediated currents. Finally, Ca2+ transients linked to the ICl,swell activation were mediated by the GPCR-independent PLC isoforms

    MADS1 maintains barley spike morphology at high ambient temperatures

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    Temperature stresses affect plant phenotypic diversity. The developmental stability of the inflorescence, required for reproductive success, is tightly regulated by the interplay of genetic and environmental factors. However, the mechanisms underpinning how plant inflorescence architecture responds to temperature are largely unknown. We demonstrate that the barley SEPALLATA MADS-box protein HvMADS1 is responsible for maintaining an unbranched spike architecture at high temperatures, while the loss-of-function mutant forms a branched inflorescence-like structure. HvMADS1 exhibits increased binding to target promoters via A-tract CArG-box motifs, which change conformation with temperature. Target genes for high-temperature-dependent HvMADS1 activation are predominantly associated with inflorescence differentiation and phytohormone signalling. HvMADS1 directly regulates the cytokinin-degrading enzyme HvCKX3 to integrate temperature response and cytokinin homeostasis, which is required to repress meristem cell cycle/division. Our findings reveal a mechanism by which genetic factors direct plant thermomorphogenesis, extending the recognized role of plant MADS-box proteins in floral development.Gang Li, Hendrik N. J. Kuijer, Xiujuan Yang, Huiran Liu, Chaoqun Shen, Jin Shi ... et al

    Assessing the spatial accessibility of hospital care in Sichuan Province, China

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    Regional disparities in geographical access to hospital care are found throughout China. Understanding variations in the spatial accessibility of hospital care has the potential to provide decision support in healthcare planning. This study examines the hospital system in the Sichuan Province in China, which provides healthcare for more than 80 million people. We examine the impacts of accessibility characterisation via the conventional measurement approach by comparing the results to those derived using a floating catchment area approach. Employing a geographical information system based on population and hospital administrative data, we conducted a provincewide study of the spatial accessibility of hospital care in Sichuan Province, China. A shortest-path analysis and the enhanced two-step floating catchment area (E2SFCA) method were implemented. Substantial differences between these two approaches were found, including a roughly 15% difference in the total number of under-served areas. Generally, spatial accessibility was higher in the eastern regions of Sichuan. More than 5.5 million people were found to have limited access, with large variations across the province. These results indicate that the official method used by policy makers in China may not capture the true nature of spatial accessibility throughout the region. We recommend that the E2SFCA method be implemented for health services research in China, providing decision makers with more accurate information when setting healthcare policies.</p

    Estimating Video Streaming QoE in the 5G Architecture Using Machine Learning

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    Compared to earlier mobile network generations, the 5G system architecture has been significantly enhanced by the introduction of network analytics functionalities and ex- tended capabilities of interacting with third party Application Functions (AFs). Combining these capabilities, new features for Quality of Experience (QoE) estimation can be designed and introduced in next generation networks. It is, however, unclear how 5G networks can collect monitoring data and application metrics, how they correlate to each other, and which techniques can be used in 5G systems for QoE estimation. This paper studies the feasibility of Machine Learning (ML) techniques for QoE estimation and evaluates their performance for a mobile video streaming use-case. A simulator has been implemented with OMNeT++ for generating traces to (i) examine the relevance of features generated from 5G monitoring data and (ii) to study the QoE estimation accuracy (iii) for a variable number of used features

    Effective transfer of micron-size graphene to microfibers for photonic applications

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    We demonstrate an effective approach to transferring micron-size CVD graphene layers onto freestanding microfibers. With micro-manipulation, the coating position and length of the graphene films can be precisely controlled. By coating micrometer-scale (e.g., 20 mu M) graphene films onto microfibers with diameters down to 1 mu m, we can achieve significantly enhanced light-graphene interaction (e.g., a low saturable-absorption threshold of 40 MW/cm(2)) and simultaneously maintain a high transmission (73% in maximum) as well. In addition, we use these microscale CVD graphene-coated microfibers (GCMs) as saturable absorbers for all-optical modulation at 1550-nm wavelength with a modulation depth of 12% and passively mode-locked fiber lasing with pulse duration down to 970 fs. (C) 2015 Elsevier Ltd. All rights reserved

    Hyper-coupling between working memory task-evoked activations and amplitude of spontaneous fluctuations in first-episode schizophrenia

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    Working memory (WM) deficit is an important component of impaired cognition in schizophrenia. However, between-studies inconsistencies as to the specific functional substrate imply that inter-individual variability (IIV) in the WM performance is associated with IIV in brain activity in schizophrenia. To examine the neural substrate of this WM IIV, we studied whether the neural mechanisms that underlie individual differences in WM capacity are the same in schizophrenia patients and healthy people. We correlated the IIV of the task-evoked brain activity and task performance during an n-back WM task with the IIV of the moment-to-moment variability in intrinsic resting-state activity, as measured by the amplitude of low-frequency fluctuations (ALFFs) and further compared this relationship between 17 patients with first-episode schizophrenia (FES) and 18 healthy controls. Between-group comparisons of the correlation patterns indicated aberrant ALFF-WM activation correlations and ALFF-WM performance correlations in the FES patients, but no significant changes were detected in any single measurement of these three characteristics. Specifically, we found increased positive ALFF-WM activation correlations in the bilateral lateral prefrontal cortices, posterior parietal cortices and fusiform gyri in the FES patients. We also observed significant increases in positive ALFF-WM performance correlations in the bilateral ventromedial prefrontal cortices in the FES patients. This hyper-coupling between the ALFF and fMRI measures during a WM task may indicate that it was difficult for the patients to detach themselves from one state to transition to another and suggests that the inefficient cortical function in schizophrenia stems from the intrinsic functional architecture of the brain. (C) 2014 Elsevier B. V. All rights reserved

    Impacts of seasonally frozen soil hydrothermal dynamics on the watershed hydrological processes inferred from a spatially distributed numerical modelling approach

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    The freeze–thaw cycle over the surface seasonally frozen soil is an important soil hydrothermal dynamic process linking land surface processes and climatic changes in the cold regions. With the advancement of frozen soil hydrothermal dynamic studies and remote sensing technology, the simulation of frozen soil hydrological processes based on the distributed numerical model has become a hotspot to better understand the impact of frozen soil hydrothermal dynamics on the watershed hydrological processes in the cold regions over a large spatial scale. However, the quantitative analysis of the impact of seasonally frozen soil hydrothermal processes on watershed runoff at long-term time scales remained an unsolved issue in the field of frozen soil hydrology. Under the framework of the watershed distributed eco-hydrological model ESSI-3, a fully distributed frozen soil hydro-thermal processes integrated modeling system (FFIMS model) was established based on the coupled water and heat transferring mechanism for frozen soil hydro-thermal process simulations in the frozen surface or at a certain depth of a watershed. By coupling the FFIMS model with the distributed eco-hydrological model ESSI-3, the impacts of seasonally frozen soil hydrothermal processes on hydrological processes were investigated from the perspective of temporal-spatial domain with the simulated hydrothermal and hydrological processes for a long-term period from 2008 to 2016 over a watershed located in the cold region of Northeastern China. The results suggested that the soil freeze–thaw cycling posed different impacts with limited significance throughout the whole hydrological processes of the watershed in different seasons. Significant impacts on the hydrological processes were particularly observed in the thawing period of a year, when soil ice meltwater contributing to the discharge of the study watershed reached to about 35% in average in this period. ESSI-3 coupled with the FFIMS modelling system obviously improved the performance of the original ESSI-3 in cold region watershed simulations, and the averaged Nash efficiency coefficients obtained increased from almost 0 to 0.77 in the thawing period of a year. The study demonstrated the importance of application of spatially distributed numerical model with physical mechanism for seasonally frozen soil water and heat transfer process simulations

    The Out-of-Plane Compression Behavior of Cross-Ply AS4/PEEK Thermoplastic Composite Laminates at High Strain Rates

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    The dynamic mechanical behavior of thermoplastic composites over a wide range of strain rates has become an important research topic for extreme environmental survivability in the fields of military protection, aircraft safety, and aerospace engineering. However, the dynamic compression response in the out-of-plane direction, which is one of the most important loading conditions resulting in the damage of composite materials, has not been investigated thoroughly when compared to in-plane compression and tensile behavior under high strain rates. Thus, we used split Hopkinson pressure bar (SHPB) tests to conduct the out-of-plane compression test of cross-ply carbon fiber-reinforced polyetheretherketone (AS4/PEEK) composite laminates. Afterward, the damage mechanism under different strain rates was characterized by the macrostructure morphologies and scanning electron microscope micrographs. Two major cases of the incomplete failure condition and complete failure condition were discussed. Dynamic stress-strain curves expound the strain rates dependencies of elastic modulus, failure strength, and failure strain. An obvious spring-back process could be observed under incomplete failure tests. For the complete failure tests, secondary loading could be observed by reconstructing and comparing the dynamic response history. Lastly, various failure modes that occurred in different loading strain rates illustrate that the damage mechanism also shows obvious strain rate sensitivity
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