The globally distributed ectoparasite Varroa destructor is a vector for viral pathogens of the Western honeybee (Apis mellifera), in particular the Iflavirus Deformed Wing Virus (DWV). In the absence of Varroa low levels DWV occur, generally causing asymptomatic infections. Conversely, Varroa-infested colonies show markedly elevated virus levels, increased overwintering colony losses, with impairment of pupal development and symptomatic workers. To determine whether changes in the virus population were due Varroa amplifying and introducing virulent virus strains and/or suppressing the host immune responses, we exposed Varroa-naïve larvae to oral and Varroa-transmitted DWV. We monitored virus levels and diversity in developing pupae and associated Varroa, the resulting RNAi response and transcriptome changes in the host. Exposed pupae were stratified by Varroa association (presence/absence) and virus levels (low/high) into three groups. Varroa-free pupae all exhibited low levels of a highly diverse DWV population, with those exposed per os (group NV) exhibiting changes in the population composition. Varroa-associated pupae exhibited either low levels of a diverse DWV population (group VL) or high levels of a near-clonal virulent variant of DWV (group VH). These groups and unexposed controls (C) could be also discriminated by principal component analysis of the transcriptome changes observed, which included several genes involved in development and the immune response. All Varroa tested contained a diverse replicating DWV population implying the virulent variant present in group VH, and predominating in RNA-seq analysis of temporally and geographically separate Varroa-infested colonies, was selected upon transmission from Varroa, a conclusion supported by direct injection of pupae in vitro with mixed virus populations. Identification of a virulent variant of DWV, the role of Varroa in its transmission and the resulting host transcriptome changes furthers our understanding of this important viral pathogen of honeybees.

BackgroundDuring the lifetime of a fermenter culture, the soil bacterium S. coelicolor undergoes a major metabolic switch from exponential growth to antibiotic production. We have studied gene expression patterns during this switch, using a specifically designed Affymetrix genechip and a high-resolution time-series of fermenter-grown samples.ResultsSurprisingly, we find that the metabolic switch actually consists of multiple finely orchestrated switching events. Strongly coherent clusters of genes show drastic changes in gene expression already many hours before the classically defined transition phase where the switch from primary to secondary metabolism was expected. The main switch in gene expression takes only 2 hours, and changes in antibiotic biosynthesis genes are delayed relative to the metabolic rearrangements. Furthermore, global variation in morphogenesis genes indicates an involvement of cell differentiation pathways in the decision phase leading up to the commitment to antibiotic biosynthesis.ConclusionsOur study provides the first detailed insights into the complex sequence of early regulatory events during and preceding the major metabolic switch in S. coelicolor, which will form the starting point for future attempts at engineering antibiotic production in a biotechnological setting.

We have used high-throughput Illumina sequencing to identify novel recombinants between Deformed wing virus (DWV) and Varroa destructor virus-1 (VDV-1), which accumulate to higher levels than DWV in both honeybees and Varroa destructor mites. The recombinants, VDV-1 VVD and VDV-1 DVD , exhibit crossovers between the 59-UTR and the regions encoding the structural (capsid) and non-structural viral proteins. This implies that the genomes are modular and that each region may evolve independently, as demonstrated in human enteroviruses. Individual honeybee pupae were infected with a mixture of observed recombinants and DWV. A strong correlation was observed between VDV-1 DVD levels in honeybee pupae and associated mites, suggesting that this recombinant, with a DWV-derived 59-UTR and non-structural protein region flanking a VDV-1-derived capsid-encoding region, is better adapted to transmission between V. destructor and honeybees than the parental DWV or a recombinant bearing the VDV-1-derived 59-UTR (VDV-1 VVD ).

In this paper we examine the bi-Hamiltonian structure of the generalized KdVhierarchies. We verify that both Hamiltonian structures take the form of Kirillov brackets on the Kac-Moody algebra, and that they define a coordinated system. Classical extended conformal algebras are obtained from the second Poisson bracket. In particular, we construct the W (l) n algebras, first discussed for the case n = 3 and l = 2 by A. Polyakov and M. Bershadsky.

Receptor-ligand couples in the cell-cell contact interface between a T cell and an antigen-presenting cell form distinct geometric patterns and undergo spatial rearrangement within the contact interface. Spatial segregation of the antigen and adhesion receptors occurs within seconds of contact, central aggregation of the antigen receptor then occurring over 1-5 min. This structure, called the immunological synapse, is becoming a paradigm for localized signaling. However, the mechanisms driving its formation, in particular spatial segregation, are currently not understood. With a reaction diffusion model incorporating thermodynamics, elasticity, and reaction kinetics, we examine the hypothesis that differing bond lengths (extracellular domain size) is the driving force behind molecular segregation. We derive two key conditions necessary for segregation: a thermodynamic criterion on the effective bond elasticity and a requirement for the seeding/nucleation of domains. Domains have a minimum length scale and will only spontaneously coalesce/aggregate if the contact area is small or the membrane relaxation distance large. Otherwise, differential attachment of receptors to the cytoskeleton is required for central aggregation. Our analysis indicates that differential bond lengths have a significant effect on synapse dynamics, i.e., there is a significant contribution to the free energy of the interaction, suggesting that segregation by differential bond length is important in cell-cell contact interfaces and the immunological synapse.

Kinesin-1 is a nanoscale molecular motor that walks towards the fast growing (plus) ends of microtubules, hauling molecular cargo to specific reaction sites in cells. Kinesin-driven transport is central to the self-organisation of eukaryotic cells and shows great promise as a tool for nano-engineering1. Recent work hints that kinesin may also play a role in modulating the stability of its microtubule track, both in vitro2,3 and in vivo4, but results are conflicting5–7 and mechanisms are unclear. Here we report a new dimension to the kinesin-microtubule interaction, whereby strong-binding state (ATP-bound and apo) kinesin-1 motor domains inhibit the shrinkage of GDP-microtubules by up to 2 orders of magnitude and expand their lattice spacing by ~1.6%. Our data reveal an unexpected mechanism by which the mechanochemical cycles of kinesin and tubulin interlock, allowing motile kinesins to influence the structure, stability and mechanics of their microtubule track.

Cell division facilitated by a contractile ring is an almost universal feature across all branches of cellular life, with the notable exception of higher plants. In all organisms that use a contractile ring for cell division, the process of cytokinesis can be divided into four distinct stages. Firstly, the cell needs to specify a location at which to place the cell division ring to ensure proper separation of the cell contents into two daughter cells. Secondly, the cell needs to be able to transport all the necessary components to this region, and construct the cell division ring reliably and efficiently. Thirdly, the cell division ring needs to generate contractile stress in a regulated manner, to physically cleave the mother cell into two daughter cells. Finally, the ring must be disassembled to allow for the final abscission and separation of the daughter cells. In this review, we will discuss some of the proposed mechanisms by which eukaryotic cells are able to complete the first three of these stages. While there is a good understanding of the mechanisms of division site specification in most organisms, and the mechanisms of actomyosin ring formation are well studied in fission and budding yeast, there is relatively poor understanding of how actomyosin interactions are able to generate contractile stresses during ring constriction, although a number of models have been proposed. We also discuss a number of myosin motor-independent mechanisms that have been proposed to generate contractile stress in various organisms.

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