Neuron-Derived Semaphorin 3A Is an Early Inducer of Vascular Permeability in Diabetic Retinopathy via Neuropilin-1

SummaryThe deterioration of the inner blood-retinal barrier and consequent macular edema is a cardinal manifestation of diabetic retinopathy (DR) and the clinical feature most closely associated with loss of sight. We provide evidence from both human and animal studies for the critical role of the classical neuronal guidance cue, semaphorin 3A, in instigating pathological vascular permeability in diabetic retinas via its cognate receptor neuropilin-1. We reveal that semaphorin 3A is induced in early hyperglycemic phases of diabetes within the neuronal retina and precipitates initial breakdown of endothelial barrier function. We demonstrate, by a series of orthogonal approaches, that neutralization of semaphorin 3A efficiently prevents diabetes-induced retinal vascular leakage in a stage of the disease when vascular endothelial growth factor neutralization is inefficient. These observations were corroborated in TgCre-Esr1/Nrp1flox/flox conditional knockout mice. Our findings identify a therapeutic target for macular edema and provide further evidence for neurovascular crosstalk in the pathogenesis of DR

The genome of the yellow potato cyst nematode, Globodera rostochiensis, reveals insights into the basis of parasitism and virulence

BACKGROUND: The yellow potato cyst nematode, Globodera rostochiensis, is a devastating plant pathogen of global economic importance. This biotrophic parasite secretes effectors from pharyngeal glands, some of which were acquired by horizontal gene transfer, to manipulate host processes and promote parasitism. G. rostochiensis is classified into pathotypes with different plant resistance-breaking phenotypes. RESULTS: We generate a high quality genome assembly for G. rostochiensis pathotype Ro1, identify putative effectors and horizontal gene transfer events, map gene expression through the life cycle focusing on key parasitic transitions and sequence the genomes of eight populations including four additional pathotypes to identify variation. Horizontal gene transfer contributes 3.5 % of the predicted genes, of which approximately 8.5 % are deployed as effectors. Over one-third of all effector genes are clustered in 21 putative ‘effector islands’ in the genome. We identify a dorsal gland promoter element motif (termed DOG Box) present upstream in representatives from 26 out of 28 dorsal gland effector families, and predict a putative effector superset associated with this motif. We validate gland cell expression in two novel genes by in situ hybridisation and catalogue dorsal gland promoter element-containing effectors from available cyst nematode genomes. Comparison of effector diversity between pathotypes highlights correlation with plant resistance-breaking. CONCLUSIONS: These G. rostochiensis genome resources will facilitate major advances in understanding nematode plant-parasitism. Dorsal gland promoter element-containing effectors are at the front line of the evolutionary arms race between plant and parasite and the ability to predict gland cell expression a priori promises rapid advances in understanding their roles and mechanisms of action.SE-vdA is supported by BBSRC grant BB/M014207/1. Sequencing was funded by BBSRC grant BB/F000642/1 to the University of Leeds and grant BB/F00334X/1 to the Wellcome Trust Sanger Institute). DRL was supported by a fellowship from The James Hutton Institute and the School of Biological Sciences, University of Edinburgh. GK was supported by a BBSRC PhD studentship. The James Hutton Institute receives funding from the Scottish Government. JAC and NEH are supported by the Wellcome Trust through its core funding of the Wellcome Trust Sanger Institute (grant 098051). This work was also supported by funding from the Canadian Safety and Security Program, project number CRTI09_462RD

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Genome annotation. (XLSX 9 kb

Experimental Investigation of Icing Effects on a Hovering Drone Rotor Performance

A scaled version of the APT70 drone rotor, typical of small to medium UAV rotors, was tested in a 9-meter-high cold chamber for a wide range of icing parameters. The drone rotor used has four blades with varying chord and twist settings. The objective of this study was to investigate icing effects on the rotor aerodynamic performance, based on experimental data, for varying rotor speeds, precipitation rates, droplet sizes and air temperatures. Aerodynamic loads were measured using the built-in load cell, and data were compared to photographs taken during testing as well as ice thickness measurements at the end of tests. The impact of each test parameter and their variations on the degradation of the rotor’s performances was evaluated. The results show that larger droplets and lower RPMs and pitch angles generate a more rapid degradation of the performances due to the airflow around the blades and tip-vortex affecting the collection efficiency of the blades. With the smaller droplets, the air temperature did not affect the performance degradation, only the type of ice accumulation. However, with the larger droplets, degradation of the performances was less severe at warmer temperatures since almost no ice accumulated at the tip and droplets were expelled before freezing

An Experimental Apparatus for Icing Tests of Low Altitude Hovering Drones

The icing facilities of the Anti-Icing Materials International Laboratory AMIL have been adapted to reproduce icing conditions on a Bell APT70 drone rotor, typical of small-to-medium UAV models. As part of an extensive icing test campaign, this paper presents the design and preliminary testing of the experimental setup and representative icing conditions calibration in the laboratory’s cold chamber. The drone rotor used has four blades with a diameter of 0.66 m and a maximum tip speed of 208 m/s. For the icing conditions, freezing rain and freezing drizzle were selected. A Liquid Water Content (LWC) calculation methodology for a rotor in hover was developed, and procedures to determine experimental LWC in the facility are presented in this paper. For the test setup, the cold chamber test section was adapted to fit the rotor and to control its ground clearance. Testing was aimed at studying the effect of rotor height h on aerodynamic performance, both with and without icing conditions. Results show no significant effect on the ground effect between h = 2 m and h = 4 m in dry runs, while the icing behavior can be largely influenced for certain conditions by the proximity of the precipitation source, which depend on the height of the rotor in these experiments

A Preliminary Approach towards Rotor Icing Modeling Using the Unsteady Vortex Lattice Method

UAV rotors are at a high risk of ice accumulation during their operations in icing conditions. Thermal ice protection systems (IPSs) are being employed as a means of protecting rotor blades from ice, yet designing the appropriate IPS with the required heating density remains a challenge. In this work, a reduced-order modeling technique based on the Unsteady Vortex Lattice Method (UVLM) is proposed as a way to predicting rotor icing and to calculate the required anti-icing heat loads. The UVLM is gaining recent popularity for aircraft and rotor modeling. This method is flexible enough to model difficult aerodynamic problems, computationally efficient compared to higher-order CFD methods and accurate enough for conceptual design problems. A previously developed implementation of the UVLM for 3D rotor aerodynamic modeling is extended to incorporate a simplified steady-state icing thermodynamic model on the stagnation line of the blade. A viscous coupling algorithm based on a modified α-method incorporates viscous data into the originally inviscid calculations of the UVLM. The algorithm also predicts the effective angle of attack at each blade radial station (r/R), which is, in turn, used to calculate the convective heat transfer for each r/R using a CFD-based correlation for airfoils. The droplet collection efficiency at the stagnation line is calculated using a popular correlation from the literature. The icing mass and heat transfer balance includes terms for evaporation, sublimation, radiation, convection, water impingement, kinetic heating, and aerodynamic heating, as well as an anti-icing heat flux. The proposed UVLM-icing coupling technique is tested by replicating the experimental results for ice accretion and anti-icing of the 4-blade rotor of the APT70 drone. Aerodynamic predictions of the UVLM for the Figure of Merit, thrust, and torque coefficients agree within 10% of the experimental measurements. For icing conditions at −5 °C, the proposed approach overestimates the required anti-icing flux by around 50%, although it sufficiently predicts the effect of aerodynamic heating on the lack of ice formation near the blade tips. At −12 °C, visualizations of ice formation at different anti-icing heating powers agree well with UVLM predictions. However, a large discrepancy was found when predicting the required anti-icing heat load. Discrepancies between the numerical and experimental data are largely owed to the unaccounted transient and 3D effects related to the icing process on the rotating blades, which have been planned for in future work

An Experimental Apparatus for Icing Tests of Low Altitude Hovering Drones

The icing facilities of the Anti-Icing Materials International Laboratory AMIL have been adapted to reproduce icing conditions on a Bell APT70 drone rotor, typical of small-to-medium UAV models. As part of an extensive icing test campaign, this paper presents the design and preliminary testing of the experimental setup and representative icing conditions calibration in the laboratory’s cold chamber. The drone rotor used has four blades with a diameter of 0.66 m and a maximum tip speed of 208 m/s. For the icing conditions, freezing rain and freezing drizzle were selected. A Liquid Water Content (LWC) calculation methodology for a rotor in hover was developed, and procedures to determine experimental LWC in the facility are presented in this paper. For the test setup, the cold chamber test section was adapted to fit the rotor and to control its ground clearance. Testing was aimed at studying the effect of rotor height h on aerodynamic performance, both with and without icing conditions. Results show no significant effect on the ground effect between h = 2 m and h = 4 m in dry runs, while the icing behavior can be largely influenced for certain conditions by the proximity of the precipitation source, which depend on the height of the rotor in these experiments