Molecular Mechanisms of White Spot Syndrome Virus Infection and Perspectives on Treatments.

Published onlineJournal ArticleReviewSince its emergence in the 1990s, White Spot Disease (WSD) has had major economic and societal impact in the crustacean aquaculture sector. Over the years shrimp farming alone has experienced billion dollar losses through WSD. The disease is caused by the White Spot Syndrome Virus (WSSV), a large dsDNA virus and the only member of the Nimaviridae family. Susceptibility to WSSV in a wide range of crustacean hosts makes it a major risk factor in the translocation of live animals and in commodity products. Currently there are no effective treatments for this disease. Understanding the molecular basis of disease processes has contributed significantly to the treatment of many human and animal pathogens, and with a similar aim considerable efforts have been directed towards understanding host-pathogen molecular interactions for WSD. Work on the molecular mechanisms of pathogenesis in aquatic crustaceans has been restricted by a lack of sequenced and annotated genomes for host species. Nevertheless, some of the key host-pathogen interactions have been established: between viral envelope proteins and host cell receptors at initiation of infection, involvement of various immune system pathways in response to WSSV, and the roles of various host and virus miRNAs in mitigation or progression of disease. Despite these advances, many fundamental knowledge gaps remain; for example, the roles of the majority of WSSV proteins are still unknown. In this review we assess current knowledge of how WSSV infects and replicates in its host, and critique strategies for WSD treatment.This work was funded by the Open Innovation Platform at the University of Exeter (Open Innovation Fund Initiative PHSW029) and by the Centre for Environment, Fisheries and Aquaculture Science (Cefas) (under seedcorn project DP318 to GDS) under the Strategic Alliance partnership between the University of Exeter and Cefas

Class-based multicast routing in interdomain scenarios

DiffServ-like domains bring new challenges to quality of service (QoS) multicast routing simply by shifting the focus from individual flows into classes of flows. Packets are marked at edge routers and receive differentiated treatment according to the class and not the flow that they belong to. DiffServ therefore became adverse to multicast, as packet replication inside the domain may require classification and remarking functions not present in core nodes. At the interdomain level, no doubt multicast QoS complexity is increased by the interleaving of DiffServ and non-Diffserv domains, making it more difficult to address QoS multicast in an end-to-end perspective. In today’s real interconnection world, classes of service have no meaning in certain links of a full interdomain path. While the problem is not new, as already pointed out, there are no real efforts to bring multicast back to a class-of-service domain without compromising its model of operation. In this article, we present an innovative multicast QoS routing strategy, clearly designed for the new class-of-service paradigm. The solution is based upon the construction of multiple trees, one per class of service available, while still allowing receivers to shift for source-specific trees in its own class of service. The strategy is presented in a full end-to-end perspective. Intradomain trees use differentiated routing paths thus helping traffic differentiation. Intradomain receivers are allowed to shift from shared trees into an adequate class-of-service source tree. At interdomain level, each class-of-service interdomain tree branch is accomplished by means of an improved path probing strategy enabling for QoS path establishment. This paper presents this new strategy, and associated protocols, for constructing several multicast and directed distribution trees, one per class of service, within each multicast group. This new strategy and associated protocols are then simulated using NS-2 platform. Simulation results are analyzed and compared with other multicast routing solutions, both at intra- and interdomain levels

De novo assembly of the Carcinus maenas transcriptome and characterization of innate immune system pathways.

Journal ArticleCopyright © 2015 Verbruggen et al.BACKGROUND: The European shore crab, Carcinus maenas, is used widely in biomonitoring, ecotoxicology and for studies into host-pathogen interactions. It is also an important invasive species in numerous global locations. However, the genomic resources for this organism are still sparse, limiting research progress in these fields. To address this resource shortfall we produced a C. maenas transcriptome, enabled by the progress in next-generation sequencing technologies, and applied this to assemble information on the innate immune system in this species. RESULTS: We isolated and pooled RNA for twelve different tissues and organs from C. maenas individuals and sequenced the RNA using next generation sequencing on an Illumina HiSeq 2500 platform. After de novo assembly a transcriptome was generated encompassing 212,427 transcripts (153,699 loci). The transcripts were filtered, annotated and characterised using a variety of tools (including BLAST, MEGAN and RSEM) and databases (including NCBI, Gene Ontology and KEGG). There were differential patterns of expression for between 1,223 and 2,741 transcripts across tissues and organs with over-represented Gene Ontology terms relating to their specific function. Based on sequence homology to immune system components in other organisms, we show both the presence of transcripts for a series of known pathogen recognition receptors and response proteins that form part of the innate immune system, and transcripts representing the RNAi, Toll-like receptor signalling, IMD and JAK/STAT pathways. CONCLUSIONS: We have produced an assembled transcriptome for C. maenas that provides a significant molecular resource for wide ranging studies in this species. Analysis of the transcriptome has revealed the presence of a series of known targets and functional pathways that form part of their innate immune system and illustrate tissue specific differences in their expression patterns.Cefas Seedcorn Contract #DP318University of Exeter’s Open Innovation PlatformWellcome Trust Institutional Strategic Support Awar

SHOC2 scaffold protein modulates daunorubicin-induced cell death through p53 modulation in lymphoid leukemia cells

SHOC2 scaffold protein has been mainly related to oncogenic ERK signaling through the RAS-SHOC2-PP1 phosphatase complex. In leukemic cells however, SHOC2 upregulation has been previously related to an increased 5-year event-free survival of pediatric pre-B acute lymphoid leukemia, suggesting that SHOC2 could be a potential prognostic marker. To address such paradoxical function, our study investigated how SHOC2 impact leukemic cells drug response. Our transcriptome analysis has shown that SHOC2 can modulate the DNA-damage mediated by p53. Notably, upon genetic inhibition of SHOC2 we observed a significant impairment of p53 expression, which in turn, leads to the blockage of key apoptotic molecules. To confirm the specificity of DNA-damage related modulation, several anti-leukemic drugs has been tested and we did confirm that the proposed mechanism impairs cell death upon daunorubicin-induced DNA damage of human lymphoid cells. In conclusion, our study uncovers new insights into SHOC2 function and reveals that this scaffold protein may be essential to activate a novel mechanism of p53-induced cell death in pre-B lymphoid cells

Rapid Photocrosslinking of Silk Hydrogels with High Cell Density and Enhanced Shape Fidelity

Silk fibroin hydrogels crosslinked through di-tyrosine bonds are clear, elastomeric constructs with immense potential in regenerative medicine applications. In this study, demonstrated is a new visible light-mediated photoredox system for di-tyrosine bond formation in silk fibroin that overcomes major limitations of current conventional enzymatic-based crosslinking. This photomediated system rapidly crosslinks silk fibroin (80%). The photocrosslinked silk hydrogels present more stable mechanical properties which do not undergo spontaneous transition to stiff, β-sheet-rich networks typically seen for enzymatically crosslinked systems. These hydrogels also support long-term culture of human articular chondrocytes, with excellent cartilage tissue formation. This system also facilitates the first demonstration of biofabrication of silk fibroin constructs in the absence of chemical modification of the protein structure or rheological additives. Cell-laden constructs with complex, ordered, graduated architectures, and high resolution (40 µm) are fabricated using the photocrosslinking system, which cannot be achieved using the enzymatic crosslinking system. Taken together, this work demonstrates the immense potential of a new crosslinking approach for fabrication of elastomeric silk hydrogels with applications in biofabrication and tissue regeneration

First-Principles Study of the Electronic and Magnetic Properties of Defects in Carbon Nanostructures

Understanding the magnetic properties of graphenic nanostructures is instrumental in future spintronics applications. These magnetic properties are known to depend crucially on the presence of defects. Here we review our recent theoretical studies using density functional calculations on two types of defects in carbon nanostructures: Substitutional doping with transition metals, and sp$^3$-type defects created by covalent functionalization with organic and inorganic molecules. We focus on such defects because they can be used to create and control magnetism in graphene-based materials. Our main results are summarized as follows: i)Substitutional metal impurities are fully understood using a model based on the hybridization between the $d$ states of the metal atom and the defect levels associated with an unreconstructed D$_{3h}$ carbon vacancy. We identify three different regimes, associated with the occupation of distinct hybridization levels, which determine the magnetic properties obtained with this type of doping; ii) A spin moment of 1.0 $\mu_B$ is always induced by chemical functionalization when a molecule chemisorbs on a graphene layer via a single C-C (or other weakly polar) covalent bond. The magnetic coupling between adsorbates shows a key dependence on the sublattice adsorption site. This effect is similar to that of H adsorption, however, with universal character; iii) The spin moment of substitutional metal impurities can be controlled using strain. In particular, we show that although Ni substitutionals are non-magnetic in flat and unstrained graphene, the magnetism of these defects can be activated by applying either uniaxial strain or curvature to the graphene layer. All these results provide key information about formation and control of defect-induced magnetism in graphene and related materials.Comment: 40 pages, 17 Figures, 62 References; Chapter 2 in Topological Modelling of Nanostructures and Extended Systems (2013) - Springer, edited by A. R. Ashrafi, F. Cataldo, A. Iranmanesh, and O. Or

Fluid-structure interaction simulation of prosthetic aortic valves : comparison between immersed boundary and arbitrary Lagrangian-Eulerian techniques for the mesh representation

In recent years the role of FSI (fluid-structure interaction) simulations in the analysis of the fluid-mechanics of heart valves is becoming more and more important, being able to capture the interaction between the blood and both the surrounding biological tissues and the valve itself. When setting up an FSI simulation, several choices have to be made to select the most suitable approach for the case of interest: in particular, to simulate flexible leaflet cardiac valves, the type of discretization of the fluid domain is crucial, which can be described with an ALE (Arbitrary Lagrangian-Eulerian) or an Eulerian formulation. The majority of the reported 3D heart valve FSI simulations are performed with the Eulerian formulation, allowing for large deformations of the domains without compromising the quality of the fluid grid. Nevertheless, it is known that the ALE-FSI approach guarantees more accurate results at the interface between the solid and the fluid. The goal of this paper is to describe the same aortic valve model in the two cases, comparing the performances of an ALE-based FSI solution and an Eulerian-based FSI approach. After a first simplified 2D case, the aortic geometry was considered in a full 3D set-up. The model was kept as similar as possible in the two settings, to better compare the simulations' outcomes. Although for the 2D case the differences were unsubstantial, in our experience the performance of a full 3D ALE-FSI simulation was significantly limited by the technical problems and requirements inherent to the ALE formulation, mainly related to the mesh motion and deformation of the fluid domain. As a secondary outcome of this work, it is important to point out that the choice of the solver also influenced the reliability of the final results

Performance and plasma urea nitrogen of immunocastrated males pigs of medium genetic potential

ABSTRACT Objective. A study was carried out to evaluate the performance and the plasma urea nitrogen (PUN) of male pigs of medium genetic potential for lean meat deposition in carcass, which underwent immunocastration. Materials and methods. Forty-five seventy-days old Large White x Landrace crossbred were used. The pigs were distributed in a randomized design in three treatments: castrated males, females and immunocastrated males. Each treatment group was replicated three times with five pigs per replicate. The trial period was of 70 days, divided into phases of growing (70 to 110 days old) and finishing (111 to 140 days old). The pigs were weighed four times: at the beginning of the trial, at the first immunocastration vaccine dose (80 days old), at the second immunocastration vaccine dose (110 days old) and just before slaughter (140 days old). Blood samples were taken on the same day that the animals were weighed. Results. Between 80 and 110 days old, there was an increase in PUN value, only for castrated males and females. No differences were found in weight gain between the studied groups within the periods. Immunocastrated males had lower feed intake than females and these had a lower feed intake than castrated males. To 110 days old, immunocastrated animals showed feed conversion ratio similar to females and better than castrated males. However, after the second dose of the vaccine, feed conversion was similar between groups. Conclusions. The benefits of immunocastration are prominent in animals with low to medium genetic potential. RESUMEN Objetivo. Se realizó un estudio para evaluar el rendimiento y la concentración de urea en plasma (PUN) de los cerdos machos de medio potencial genético de carne magra en la canal sometidos a la inmunocastración. Materiales y métodos. Se utilizaron 45 cerdos de 70 días de edad Landrace x Large White. Los animales se distribuyeron en un diseño completamente al azar con tres tratamientos: machos castrados, hembras y machos inmunocastrados. Cada tratamiento consistió en tres repeticiones, con cinco animales por réplica. El período experimental fue de 70 días, divididos en las etapas de crecimiento (70 a 110 días de edad) y terminación (111 a 140 días de edad). Los cerdos fueron pesados cuatro veces: al inicio del experimento, en la primera dosis de vacuna de inmunocastración (80 días de edad), en la segunda dosis de la vacuna de inmunocastración (110 días de edad) y antes de el sacrificio (140 días de edad). Las muestras de sangre se recogieron en el mismo día en que se pesaron los animales. Resultados. Entre 80 y 110 días de edad, hubo un aumento en la cantidad de PUN, sólo para machos castrados y hembras. No hubo diferencias en la ganancia de peso entre los grupos en ninguno de los períodos estudiados. Machos inmunocastrados tuvieron menor consumo de alimento que las hembras y éstas mostraron un menor consumo que los machos castrados. En 110 días de edad, los animales inmunocastrados mostraron la conversión de alimento similar a las hembras y mejor que los machos castrados. Sin embargo, después de la segunda dosis de la vacuna, la conversión alimenticia fue similar entre los grupos. Conclusiones. Los beneficios de inmunocastración son prominentes en animales con bajo a médio potencial genético.

Electron quantum metamaterials in van der Waals heterostructures

In recent decades, scientists have developed the means to engineer synthetic periodic arrays with feature sizes below the wavelength of light. When such features are appropriately structured, electromagnetic radiation can be manipulated in unusual ways, resulting in optical metamaterials whose function is directly controlled through nanoscale structure. Nature, too, has adopted such techniques -- for example in the unique coloring of butterfly wings -- to manipulate photons as they propagate through nanoscale periodic assemblies. In this Perspective, we highlight the intriguing potential of designer sub-electron wavelength (as well as wavelength-scale) structuring of electronic matter, which affords a new range of synthetic quantum metamaterials with unconventional responses. Driven by experimental developments in stacking atomically layered heterostructures -- e.g., mechanical pick-up/transfer assembly -- atomic scale registrations and structures can be readily tuned over distances smaller than characteristic electronic length-scales (such as electron wavelength, screening length, and electron mean free path). Yet electronic metamaterials promise far richer categories of behavior than those found in conventional optical metamaterial technologies. This is because unlike photons that scarcely interact with each other, electrons in subwavelength structured metamaterials are charged, and strongly interact. As a result, an enormous variety of emergent phenomena can be expected, and radically new classes of interacting quantum metamaterials designed