Spatial model of convective solute transport in brain extracellular space does not support a "glymphatic" mechanism.

A "glymphatic system," which involves convective fluid transport from para-arterial to paravenous cerebrospinal fluid through brain extracellular space (ECS), has been proposed to account for solute clearance in brain, and aquaporin-4 water channels in astrocyte endfeet may have a role in this process. Here, we investigate the major predictions of the glymphatic mechanism by modeling diffusive and convective transport in brain ECS and by solving the Navier-Stokes and convection-diffusion equations, using realistic ECS geometry for short-range transport between para-arterial and paravenous spaces. Major model parameters include para-arterial and paravenous pressures, ECS volume fraction, solute diffusion coefficient, and astrocyte foot-process water permeability. The model predicts solute accumulation and clearance from the ECS after a step change in solute concentration in para-arterial fluid. The principal and robust conclusions of the model are as follows: (a) significant convective transport requires a sustained pressure difference of several mmHg between the para-arterial and paravenous fluid and is not affected by pulsatile pressure fluctuations; (b) astrocyte endfoot water permeability does not substantially alter the rate of convective transport in ECS as the resistance to flow across endfeet is far greater than in the gaps surrounding them; and (c) diffusion (without convection) in the ECS is adequate to account for experimental transport studies in brain parenchyma. Therefore, our modeling results do not support a physiologically important role for local parenchymal convective flow in solute transport through brain ECS

The consequences of replicating in the wrong orientation: Bacterial chromosome duplication without an active replication origin

Chromosome replication is regulated in all organisms at the assembly stage of the replication machinery at specific origins. In Escherichia coli the DnaA initiator protein regulates the assembly of replication forks at oriC. This regulation can be undermined by defects in nucleic acid meta¬bolism. In cells lacking RNase HI replication initiates indepen¬dently of DnaA and oriC, presumably at persisting R-loops. A similar mechanism was assumed for origin-independent synthesis in cells lacking RecG. However, recently we suggested that this synthesis initiates at intermediates resulting from replication fork fusions. Here we present data suggesting that in cells lacking RecG or RNase HI origin-independent synthesis arises by different mechanisms, indicative of these two proteins having different roles in vivo. Our data support the idea that RNase HI processes R-loops, while RecG is required to process replication fork fusion intermediates. However, regardless of how origin-independent synthesis is initiated, a fraction of forks will proceed in an orientation opposite to normal. We show that the resulting head-on encounters with transcription threaten cell viability, especially if taking place in highly-transcribed areas. Thus, despite their different functions, RecG and RNase HI are both important factors for maintaining replication control and orientation. Their absence causes severe replication problems, highlighting the advantages of the normal chromosome arrangement, which exploits a single origin to control the number of forks and their orientation relative to transcription, and a defined termination area to contain fork fusions. Any changes to this arrangement endanger cell cycle control, chromosome dynamics and, ultimately, cell viability.This work was supported by the Royal Society (RG110414 to C.J.R.) and The Biotechnology and Biological Sciences Research Council (BB/K015729/1 to C.J.R.)

Tears

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Evaluation of the DNDC Model to Estimate Soil Parameters, Crop Yield and Nitrous Oxide Emissions for Alternative Long-Term Multi-Cropping Systems in the North China Plain

Funding Information: Funding: National Natural Science Foundation of China (41830751), Hainan University Startup Fund (KYQD(ZR)-20098), the N Circle–a BBSRC-Newton Funded project (BB/N013484/1) and EU Horizon 2020 Programme (Super-G). We thank Bing Gao for providing measurement datasets and Xinping Chen for managing the field trial.Peer reviewedPublisher PD

Estimating the effect of nitrogen fertilizer on the greenhouse gas balance of soils in Wales under current and future climate

The Welsh Government is committed to reduce greenhouse gas (GHG) emissions from agricultural systems and combat the effects of future climate change. In this study, the ECOSSE model was applied spatially to estimate GHG and soil organic carbon (SOC) fluxes from three major land uses (grass, arable and forest) in Wales. The aims of the simulations were: (1) to estimate the annual net GHG balance for Wales; (2) to investigate the efficiency of the reduced nitrogen (N) fertilizer goal of the sustainable land management scheme (Glastir), through which the Welsh Government offers financial support to farmers and land managers on GHG flux reduction; and (3) to investigate the effects of future climate change on the emissions of GHG and plant net primary production (NPP). Three climate scenarios were studied: baseline (1961–1990) and low and high emission climate scenarios (2015–2050). Results reveal that grassland and cropland are the major nitrous oxide (N2O) emitters and consequently emit more GHG to the atmosphere than forests. The overall average simulated annual net GHG balance for Wales under baseline climate (1961–1990) is equivalent to 0.2 t CO2e ha-1 y-1 which gives an estimate of total annual net flux for Wales of 0.34 Mt CO2e y-1. Reducing N fertilizer by 20 and 40 % could reduce annual net GHG fluxes by 7 and 25 %, respectively. If the current N fertilizer application rate continues, predicted climate change by the year 2050 would not significantly affect GHG emissions or NPP from soils in Wales

Nitrogen Surplus Benchmarks for Controlling N Pollution in the Main Cropping Systems of China

This study was financially supported by National Key Research and Development Project of China (2017YFD0200105), China−UK PhD Placement Programme funded by CSC (201603780082), and contributes to “N-Circle” and “CINAg” projects funded by the Newton Fund via UK BBSRC/NERC (grants BB/N013484/1 and BB/N013468/1, respectively).Peer reviewedPostprintPostprin