Biology subjects

Heurich, M.

Publications and source records attributed to Heurich, M..

4 recordsLinked to original sources

bioRxiv2021

imageseg: an R package for deep learning-based image segmentation

O_LIConvolutional neural networks (CNNs) and deep learning are powerful and robust tools for ecological applications. CNNs can perform very well in various tasks, especially for visual tasks and image data. Image segmentation (the classification of all pixels in images) is one such task and can for example be used to assess forest vertical and horizontal structure. While such methods have been suggested, widespread adoption in ecological research has been slow, likely due to technical difficulties in implementation of CNNs and lack of toolboxes for ecologists. C_LIO_LIHere, we present R package imageseg which implements a workflow for general-purpose image segmentation using CNNs and the U-Net architecture in R. The workflow covers data (pre)processing, model training, and predictions. We illustrate the utility of the package with two models for forest structural metrics: tree canopy density and understory vegetation density. We trained the models using large and diverse training data sets from a variety of forest types and biomes, consisting of 3288 canopy images (both canopy cover and hemispherical canopy closure photographs) and 1468 understory vegetation images. C_LIO_LIOverall classification accuracy of the models was high with a Dice score of 0.91 for the canopy model and 0.89 for the understory vegetation model (assessed with 821 and 367 images, respectively), indicating robustness to variation in input images and good generalization strength across forest types and biomes. C_LIO_LIThe package and its workflow allow simple yet powerful assessments of forest structural metrics using pre-trained models. Furthermore, the package facilitates custom image segmentation with multiple classes and based on color or grayscale images, e.g. in cell biology or for medical images. Our package is free, open source, and available from CRAN. It will enable easier and faster implementation of deep learning-based image segmentation within R for ecological applications and beyond. C_LI

ecology↗

bioRxiv2021

Eurasian lynx populations in Western Europe: What prospects for the next 50 years?

Persistence of populations may be uncertain for large carnivore species, especially for those established in human-dominated landscapes. Here, we studied the Eurasian lynx in Western Europe established in the Upper Rhine meta-population (i.e., Jura, Vosges-Palatinian and Black Forest populations) and the Alpine population. These populations are currently considered endangered or critically endangered due to high anthropogenic mortality, small population size and low genetic diversity, and isolation. We assessed lynx persistence over a 50-year time horizon by implementing a spatially-explicit individual-based model, while accounting for road mortality and habitat selection. Forecasts showed a steady growth rapidly reaching a more stable phase for the Alpine and Jura populations, and a more heterogeneous positive growth with less precision for the Vosges-Palatinian and Black Forest populations. Exchanges of individuals between populations were limited, the Jura population playing the role of a crossroad. Finally, the persistence of lynx in Western Europe seems likely on a large scale over the next 50 years. Indeed, simulations showed high female occupancy as well as average lynx density over the core areas of the four studied populations. Nevertheless, these results should be interpreted with the model limitations in mind, concerning the absence of movement barriers and inbreeding depression.

ecology↗

bioRxiv2021

Complement Regulator Factor H is a Cofactor for Thrombin in both Pro- and Anticoagulant Roles

BackgroundComplement FH (FH) is a key regulator of complement activity whereas thrombin (FIIa) is central to hemostasis with both pro- and anticoagulant functions. Both have separately been shown to have auxiliary activities across the two systems. The purpose of this study was to determine the effect of FH on pro- and anti-coagulant functions and investigate the interaction between FH and thrombin. MethodsTail bleeding time and hemolysis were measured in FH-deficient mice (CFH-/-). Activated partial thromboplastin time (aPTT) was determined in FH-depleted human plasma. FH effect on fibrin clot generation was investigated in turbidity assays and on activated protein C (APC) generation. Binding affinity of thrombin with FH was determined using surface plasmon resonance (SPR). ResultsTail bleeding time in CFH-/- mice was significantly prolonged compared to wild type mice. The aPTT in FH-depleted human plasma was elevated compared to normal plasma and restored by adding back FH to depleted plasma. Accordingly, FH enhanced thrombin-mediated fibrin clot generation by shortening lag time, increasing rate of clot formation and maximum turbidity, and affected clot structure. Despite this, FH also increased the rate of thrombin-mediated protein C (PC) activation, both in the presence and absence of soluble recombinant thrombomodulin (TM). Nanomolar affinity binding of FH with thrombin, but not prothrombin, was confirmed. ConclusionComplement FH binds thrombin with strong affinity and acts as a novel cofactor that enhances both pro- and anticoagulant actions of thrombin. These data highlight an important role for FH in hemostasis. Key pointsO_LIAbsence of FH prolongs tail bleeding time in CFH-/- mice and activated partial thromboplastin time (aPTT) is elevated in human FH-depleted plasma. C_LIO_LIFH acts a cofactor for thrombin by enhancing fibrin generation, altering fibrin clot structure and enhancing TM-thrombin mediated protein C activation C_LI

immunology↗

bioRxiv2021

The Structure of ChAdOx1/AZD-1222 Reveals Interactions with CAR and PF4 with Implications for Vaccine-induced Immune Thrombotic Thrombocytopenia

Adenovirus derived vectors, based on chimpanzee adenovirus Y25 (ChAdOx1) and human adenovirus type 26 are proving critical in combatting the 2019 SARS-CoV-2 pandemic. Following emergency use authorisation, scale up in vaccine administration has inevitably revealed vaccine related adverse effects; too rare to observe even in large Phase-III clinical trials. These include vaccine-induced thrombotic thrombocytopenia (VITT), an ultra-rare adverse event in which patients develop life-threatening blood clots 5-24 days following vaccination. To investigate vector-host interactions of ChAdOx1 underpinning VITT we solved the structure of the ChAdOx1 capsid by CryoEM, and the structure of the primary receptor tropism determining fiber-knob protein by crystallography. These structural insights have enabled us to unravel key protein interactions involved in ChAdOx1 cell entry and a possible means by which it may generate misplaced immunity to platelet factor 4 (PF4), a protein involved in coagulation. We use in vitro cell binding assays to show that the fiber-knob protein uses coxsackie and adenovirus receptor (CAR) as a high affinity binding partner, while it does not form a stable interface with CD46. Computational simulations identified a putative mechanism by which the ChAdOx1 capsid interacts with PF4 by binding in the spaces between hexon proteins, with downstream implications for the causes of VITT. SummaryWe present the structure of the ChAdOx1 viral vector, derived from chimpanzee adenovirus Y25 at 4.2[A] resolution1. ChAdOx1 is in global use in the AstraZeneca vaccine, ChAdOx1 nCoV-19/AZD-1222, to combat the SARS-CoV-2 coronavirus pandemic. Recently observed, rare, adverse events make detailed mechanistic understanding of this vector key to informing proper treatment of affected patients and the development of safer viral vectors. Here, we determine a primary mechanism ChAdOx1 uses to attach to cells is coxsackie and adenovirus receptor (CAR), a protein which is identical in humans and chimpanzees. We demonstrate the vector does not form a stable CD46 interaction, a common species B adenovirus receptor, via its primary attachment protein. Further, we reveal the surface of the ChAdOx1 viral capsid has a strong electronegative potential. Molecular simulations suggest this charge, together with shape complementarity, are a mechanism by which an oppositely charged protein, platelet factor 4 (PF4) may bind the vector surface. PF4 is a key protein involved in the formation of blood clots2, and the target of auto-antibodies in heparin-induced immune thrombotic thrombocytopenia (HITT)3, an adverse reaction to heparin therapy which presents similarly to vaccine-induced immune thrombotic thrombocytopenia (VITT), a rare complication of ChAdOx1 nCoV-19 vaccination4-6. We propose a mechanism in which the ChAdOx1-PF4 complex may stimulate the production of antibodies against PF4, leading to delayed blood clot formation, as observed in VITT.

molecular biology↗