Rapid and Accurate Assessment of GPCR-Ligand Interactions Using the Fragment Molecular Orbital-Based Density-Functional Tight-Binding Method

The reliable and precise evaluation of receptor–ligand interactions and pair-interaction energy is an essential element of rational drug design. While quantum mechanical (QM) methods have been a promising means by which to achieve this, traditional QM is not applicable for large biological systems due to its high computational cost. Here, the fragment molecular orbital (FMO) method has been used to accelerate QM calculations, and by combining FMO with the density-functional tight-binding (DFTB) method we are able to decrease computational cost 1000 times, achieving results in seconds, instead of hours. We have applied FMO-DFTB to three different GPCR–ligand systems. Our results correlate well with site directed mutagenesis data and findings presented in the published literature, demonstrating that FMO-DFTB is a rapid and accurate means of GPCR–ligand interactions

Novel constructs and 1-step chromatography protocols for the production of Porcine Circovirus 2d (PCV2d) and Circovirus 3 (PCV3) subunit vaccine candidates

Porcine circovirus type 2 (PCV2) has been a major problem for the pig production industry worldwide for decades. While the majority of commercially available vaccines are based on the original PCV2a genotype, the current dominant genotype is PCV2d. The notable differences between genotypes could lead to incomplete cross-protection. Moreover, most current subunit PCV2 vaccines are generated from expensive insect cell culture technology. In this work, we present a new workflow for production of an updated and relatively inexpensive PCV2d vaccine candidate. After expression in fed-batch Escherichia coli fermentation systems with a simple one-step ion-exchange chromatography purification protocol, the yield of purified PCV2d-based antigen reached over 1 g per litre bacterial culture. Using similar procedures, we also demonstrated even higher PCV2d-based antigen yields from a chimeric PCV2d-PCV3 capsid construct, which is cleaved during fermentation to release PCV2d- and PCV3-related polypeptides. Although the PCV2d-based recombinant protein from this protocol did not form viral-like particles as analysed by size-exclusion chromatography, it could effectively induce capsid-specific and PCV2d-neutralising antibodies in immunised animals, indicating significant potential as a new vaccine candidate that can be easily manufactured at commercial scale

West Highland White Terriers under primary veterinary care in the UK in 2016: demography, mortality and disorders

The West Highland White Terrier (WHWT) is a relatively common breed in the UK, although Kennel Club registrations have declined in recent years. The VetCompass™ Programme collates de-identified clinical data from primary-care veterinary practices in the UK for epidemiological research. Using VetCompass clinical data, this study aimed to characterise the demography, longevity and common disorders of WHWTs under primary veterinary care in the UK

An intuitive Python interface for Bioconductor libraries demonstrates the utility of language translators

<p>Abstract</p> <p>Background</p> <p>Computer languages can be domain-related, and in the case of multidisciplinary projects, knowledge of several languages will be needed in order to quickly implements ideas. Moreover, each computer language has relative strong points, making some languages better suited than others for a given task to be implemented. The Bioconductor project, based on the R language, has become a reference for the numerical processing and statistical analysis of data coming from high-throughput biological assays, providing a rich selection of methods and algorithms to the research community. At the same time, Python has matured as a rich and reliable language for the agile development of prototypes or final implementations, as well as for handling large data sets.</p> <p>Results</p> <p>The data structures and functions from Bioconductor can be exposed to Python as a regular library. This allows a fully transparent and native use of Bioconductor from Python, without one having to know the R language and with only a small community of <it>translators</it> required to know both. To demonstrate this, we have implemented such Python representations for key infrastructure packages in Bioconductor, letting a Python programmer handle annotation data, microarray data, and next-generation sequencing data.</p> <p>Conclusions</p> <p>Bioconductor is now not solely reserved to R users. Building a Python application using Bioconductor functionality can be done just like if Bioconductor was a Python package. Moreover, similar principles can be applied to other languages and libraries. Our Python package is available at: <url>http://pypi.python.org/pypi/rpy2-bioconductor-extensions/</url></p

Anarchy in the UK: Detailed genetic analysis of worker reproduction in a naturally occurring British anarchistic honeybee, Apis mellifera, colony using DNA microsatellites

Anarchistic behaviour is a very rare phenotype of honeybee colonies. In an anarchistic colony, many workers’ sons are reared in the presence of the queen. Anarchy has previously been described in only two Australian colonies. Here we report on a first detailed genetic analysis of a British anarchistic colony. Male pupae were present in great abundance above the queen excluder, which was clearly indicative of extensive worker reproduction and is the hallmark of anarchy. Seventeen microsatellite loci were used to analyse these male pupae, allowing us to address whether all the males were indeed workers’ sons, and how many worker patrilines and individual workers produced them. In the sample, 95 of 96 of the males were definitely workers’ sons. Given that ≈ 1% of workers’ sons were genetically indistinguishable from queen’s sons, this suggests that workers do not move any queen-laid eggs between the part of the colony where the queen is present to the area above the queen excluder which the queen cannot enter. The colony had 16 patrilines, with an effective number of patrilines of 9.85. The 75 males that could be assigned with certainty to a patriline came from 7 patrilines, with an effective number of 4.21. They were the offspring of at least 19 workers. This is in contrast to the two previously studied Australian naturally occurring anarchist colonies, in which most of the workers’ sons were offspring of one patriline. The high number of patrilines producing males leads to a low mean relatedness between laying workers and males of the colony. We discuss the importance of studying such colonies in the understanding of worker policing and its evolution

Multidimensional ground reaction forces and moments from wearable sensor accelerations via deep learning

Objective: Monitoring athlete internal workload exposure, including prevention of catastrophic non-contact knee injuries, relies on the existence of a custom early-warning detection system. This system must be able to estimate accurate, reliable, and valid musculoskeletal joint loads, for sporting maneuvers in near real-time and during match play. However, current methods are constrained to laboratory instrumentation, are labor and cost intensive, and require highly trained specialist knowledge, thereby limiting their ecological validity and volume deployment. Methods: Here we show that kinematic data obtained from wearable sensor accelerometers, in lieu of embedded force platforms, can leverage recent supervised learning techniques to predict in-game near real-time multidimensional ground reaction forces and moments (GRF/M). Competing convolutional neural network (CNN) deep learning models were trained using laboratory-derived stance phase GRF/M data and simulated sensor accelerations for running and sidestepping maneuvers derived from nearly half a million legacy motion trials. Then, predictions were made from each model driven by five sensor accelerations recorded during independent inter-laboratory data capture sessions. Results: Despite adversarial conditions, the proposed deep learning workbench achieved correlations to ground truth, by GRF component, of vertical 0.9663, anterior 0.9579 (both running), and lateral 0.8737 (sidestepping). Conclusion: The lessons learned from this study will facilitate the use of wearable sensors in conjunction with deep learning to accurately estimate near real-time on-field GRF/M. Significance: Coaching, medical, and allied health staff can use this technology to monitor a range of joint loading indicators during game play, with the ultimate aim to minimize the occurrence of non-contact injuries in elite and community-level sports

Demography and disorders of German Shepherd Dogs under primary veterinarycare in the UK

The German Shepherd Dog (GSD) has been widely used for a variety of working roles. However, concerns for the health and welfare of the GSD have been widely aired and there is evidence that breed numbers are now in decline in the UK. Accurate demographic and disorder data could assist with breeding and clinical prioritisation. The VetCompassTM Programme collects clinical data on dogs under primary veterinary care in the UK. This study included all VetCompassTM dogs under veterinary care during 2013. Demographic, mortality and clinical diagnosis data on GSDs were extracted and reported

Black Stork Down: Military Discourses in Bird Conservation in Malta

Tensions between Maltese hunters and bird conservation NGOs have intensified over the past decade. Conservation NGOs have become frustrated with the Maltese State for conceding to the hunter lobby and negotiating derogations from the European Union’s Bird Directive. Some NGOs have recently started to organize complex field-operations where volunteers are trained to patrol the landscape, operate drones and other surveillance technologies, detect illegalities, and lead police teams to arrest poachers. We describe the sophisticated military metaphors which conservation NGOs have developed to describe, guide and legitimize their efforts to the Maltese public and their fee-paying members. We also discuss why such groups might be inclined to adopt these metaphors. Finally, we suggest that anthropological studies of discourse could help understand delicate contexts such as this where conservation NGOs, hunting associations and the State have ended in political deadlock

Entanglement generation outside a Schwarzschild black hole and the Hawking effect

We examine the Hawking effect by studying the asymptotic entanglement of two mutually independent two-level atoms placed at a fixed radial distance outside a Schwarzschild black hole in the framework of open quantum systems. We treat the two-atom system as an open quantum system in a bath of fluctuating quantized massless scalar fields in vacuum and calculate the concurrence, a measurement of entanglement, of the equilibrium state of the system at large times, for the Unruh, Hartle-Hawking and Boulware vacua respectively. We find, for all three vacuum cases, that the atoms turn out to be entangled even if they are initially in a separable state as long as the system is not placed right at the even horizon. Remarkably, only in the Unruh vacuum, will the asymptotic entanglement be affected by the backscattering of the thermal radiation off the space-time curvature. The effect of the back scatterings on the asymptotic entanglement cancels in the Hartle-Hawking vacuum case.Comment: 15 pages, no figures, Revte