Heparanase inhibition as a systemic approach to protect the endothelial glycocalyx and prevent microvascular complications in diabetes.

BACKGROUND: Diabetes mellitus is a chronic disease which is detrimental to cardiovascular health, often leading to secondary microvascular complications, with huge global health implications. Therapeutic interventions that can be applied to multiple vascular beds are urgently needed. Diabetic retinopathy (DR) and diabetic kidney disease (DKD) are characterised by early microvascular permeability changes which, if left untreated, lead to visual impairment and renal failure, respectively. The heparan sulphate cleaving enzyme, heparanase, has previously been shown to contribute to diabetic microvascular complications, but the common underlying mechanism which results in microvascular dysfunction in conditions such as DR and DKD has not been determined. METHODS: In this study, two mouse models of heparan sulphate depletion (enzymatic removal and genetic ablation by endothelial specific Exotosin-1 knock down) were utilized to investigate the impact of endothelial cell surface (i.e., endothelial glycocalyx) heparan sulphate loss on microvascular barrier function. Endothelial glycocalyx changes were measured using fluorescence microscopy or transmission electron microscopy. To measure the impact on barrier function, we used sodium fluorescein angiography in the eye and a glomerular albumin permeability assay in the kidney. A type 2 diabetic (T2D, db/db) mouse model was used to determine the therapeutic potential of preventing heparan sulphate damage using treatment with a novel heparanase inhibitor, OVZ/HS-1638. Endothelial glycocalyx changes were measured as above, and microvascular barrier function assessed by albumin extravasation in the eye and a glomerular permeability assay in the kidney. RESULTS: In both models of heparan sulphate depletion, endothelial glycocalyx depth was reduced and retinal solute flux and glomerular albumin permeability was increased. T2D mice treated with OVZ/HS-1638 had improved endothelial glycocalyx measurements compared to vehicle treated T2D mice and were simultaneously protected from microvascular permeability changes associated with DR and DKD. CONCLUSION: We demonstrate that endothelial glycocalyx heparan sulphate plays a common mechanistic role in microvascular barrier function in the eye and kidney. Protecting the endothelial glycocalyx damage in diabetes, using the novel heparanase inhibitor OVZ/HS-1638, effectively prevents microvascular permeability changes associated with DR and DKD, demonstrating a novel systemic approach to address diabetic microvascular complications.

Women's probability of conception is associated with their preference for flirtatious but not masculine facial movement.

Women's preferences for facial structure vary over the menstrual cycle. Little is known, however, as to how preferences for behavior may be influenced by hormonal factors. Here, we demonstrate that social properties of facial motion influence attractiveness judgments in the absence of other cues, and that women's preferences for these displays vary over the menstrual cycle, as has been demonstrated for structural traits of men's faces in static stimuli. We produced shape-standardized facial models that were animated with male movement and assessed for flirtatiousness by 16 women and attractiveness by 47 women. In fertile phases of the menstrual cycle, women showed stronger preferences for flirtatious movement, but not for absolute movement. These data show that women (1) recognize specific mating-relevant social cues in male facial movement and (2) are differentially influenced by these cues at different phases of the menstrual cycle. This preference for flirtatiousness may promote the adaptive allocation of mating effort towards men who are, in turn, likely to respond positively.

Quantifying defence cascade responses as indicators of pig affect and welfare using computer vision methods.

Affective states are key determinants of animal welfare. Assessing such states under field conditions is thus an important goal in animal welfare science. The rapid Defence Cascade (DC) response (startle, freeze) to sudden unexpected stimuli is a potential indicator of animal affect; humans and rodents in negative affective states often show potentiated startle magnitude and freeze duration. To be a practical field welfare indicator, quick and easy measurement is necessary. Here we evaluate whether DC responses can be quantified in pigs using computer vision. 280 video clips of induced DC responses made by 12 pigs were analysed by eye to provide 'ground truth' measures of startle magnitude and freeze duration which were also estimated by (i) sparse feature tracking computer vision image analysis of 200 Hz video, (ii) load platform, (iii) Kinect depth camera, and (iv) Kinematic data. Image analysis data strongly predicted ground truth measures and were strongly positively correlated with these and all other estimates of DC responses. Characteristics of the DC-inducing stimulus, pig orientation relative to it, and 'relaxed-tense' pig behaviour prior to it moderated DC responses. Computer vision image analysis thus offers a practical approach to measuring pig DC responses, and potentially pig affect and welfare, under field conditions.

MegaParallax: Casual 360° Panoramas with Motion Parallax.

The ubiquity of smart mobile devices, such as phones and tablets, enables users to casually capture 360° panoramas with a single camera sweep to share and relive experiences. However, panoramas lack motion parallax as they do not provide different views for different viewpoints. The motion parallax induced by translational head motion is a crucial depth cue in daily life. Alternatives, such as omnidirectional stereo panoramas, provide different views for each eye (binocular disparity), but they also lack motion parallax as the left and right eye panoramas are stitched statically. Methods based on explicit scene geometry reconstruct textured 3D geometry, which provides motion parallax, but suffers from visible reconstruction artefacts. The core of our method is a novel multi-perspective panorama representation, which can be casually captured and rendered with motion parallax for each eye on the fly. This provides a more realistic perception of panoramic environments which is particularly useful for virtual reality applications. Our approach uses a single consumer video camera to acquire 200-400 views of a real 360° environment with a single sweep. By using novel-view synthesis with flow-based blending, we show how to turn these input views into an enriched 360° panoramic experience that can be explored in real time, without relying on potentially unreliable reconstruction of scene geometry. We compare our results with existing omnidirectional stereo and image-based rendering methods to demonstrate the benefit of our approach, which is the first to enable casual consumers to capture and view high-quality 360° panoramas with motion parallax.