Kaposi's sarcoma-associated herpesvirus ORF57 protein: exploiting all stages of viral mRNA processing

Nuclear mRNA export is a highly complex and regulated process in cells. Cellular transcripts must undergo successful maturation processes, including splicing, 5'-, and 3'-end processing, which are essential for assembly of an export competent ribonucleoprotein particle. Many viruses replicate in the nucleus of the host cell and require cellular mRNA export factors to efficiently export viral transcripts. However, some viral mRNAs undergo aberrant mRNA processing, thus prompting the viruses to express their own specific mRNA export proteins to facilitate efficient export of viral transcripts and allowing translation in the cytoplasm. This review will focus on the Kaposi’s sarcoma-associated herpesvirus ORF57 protein, a multifunctional protein involved in all stages of viral mRNA processing and that is essential for virus replication. Using the example of ORF57, we will describe cellular bulk mRNA export pathways and highlight their distinct features, before exploring how the virus has evolved to exploit these mechanisms

A model of coppice biomass recovery for mallee-form eucalypts

Planting mallee-form eucalypts amongst crops has the potential to remedy environmental degradation caused by land clearing in low rainfall regions, whilst also providing income through carbon-sequestration or periodic coppicing. Management options can be supported by models of biomass and coppice recovery, and this paper presents the first empirical coppice growth model for mallee eucalypts. Uncoppiced and coppiced belt-planted Eucalyptus polybractea, E. loxophleba and E. kochii were harvested and roots excavated to provide estimates of shoot and root biomass for analysis and model development. Allometric models of shoot biomass were appropriate for both uncoppiced and coppiced trees, but models of root/total biomass ratio for coppice depended on site quality and age, and could not be modelled allometrically. Mean root/total biomass proportions for uncoppiced trees were estimated (with standard errors) to be 0.38 (0.009), 0.50 (0.031), and 0.46 (0.021) for E. polybractea, E. loxophleba, and E. kochii respectively and were sensitive to site quality but insensitive to age. The time taken to regain pre-coppice shoot biomass was about half that of full pre-cut root/total biomass ratio recovery, and was affected by coppicing age and site quality. A conceptual model of coppice growth indicated that coppiced stands may produce more total biomass than uncoppiced stands of the same age

Convex optimization on CAT(0) cubical complexes

We consider geodesically convex optimization problems involving distances to a finite set of points $A$ in a CAT(0) cubical complex. Examples include the minimum enclosing ball problem, the weighted mean and median problems, and the feasibility and projection problems for intersecting balls with centers in $A$. We propose a decomposition approach relying on standard Euclidean cutting plane algorithms. The cutting planes are readily derivable from efficient algorithms for computing geodesics in the complex

Recognizing weighted means in geodesic spaces

Geodesic metric spaces support a variety of averaging constructions for given finite sets. Computing such averages has generated extensive interest in diverse disciplines. Here we consider the inverse problem of recognizing computationally whether or not a given point is such an average, exactly or approximately. In nonpositively curved spaces, several averaging notions, including the usual weighted barycenter, produce the same "mean set". In such spaces, at points where the tangent cone is a Euclidean space, the recognition problem reduces to Euclidean projection onto a polytope. Hadamard manifolds comprise one example. Another consists of CAT(0) cubical complexes, at relative-interior points: the recognition problem is harder for general points, but we present an efficient semidefinite-programming-based algorithm

Hybridisation and detection of a hybrid zone between mesic and desert ragworts (Senecio) across an aridity gradient in the eastern Mediterranean

Background: Hybrid zones provide excellent opportunities for studying plant adaptation and speciation. Aims: We tested whether two herbaceous species of Senecio, S. vernalis and S. glaucus, hybridise in the eastern Mediterranean region and form a hybrid zone across an aridity gradient in the Jordan Rift Valley. Methods: Allozyme variation surveyed across both species was analysed by the programme STRUCTURE to assign individuals to genetic groups and determine levels of admixture. Populations in the Jordan Rift Valley were subsequently subjected to a cline analysis. Results: STRUCTURE showed that interspecific hybrids were produced at low frequency along the Israeli coastal plain where S. glaucus is represented by ssp. glaucus. In contrast, hybrids were more commonly produced in central populations of the Jordan Rift Valley. Here, the two species form a hybrid zone with S. vernalis occurring in mesic sites to the north and S. glaucus (ssp. coronopifolius) in arid sites to the south. Cline analysis showed that the hybrid zone is centred towards the northern end of the Dead Sea, but the analysis failed to distinguish how it is maintained. Conclusions: Future detailed genetic and ecological analysis of the Senecio hybrid zone should improve our understanding of plant adaptation and speciation across aridity gradients

Glacial meltwater identification in the Amundsen Sea

Pine Island Ice Shelf, in the Amundsen Sea, is losing mass because of warm ocean waters melting the ice from below. Tracing meltwater pathways from ice shelves is important for identifying the regions most affected by the increased input of this water type. Here, optimum multiparameter analysis is used to deduce glacial meltwater fractions from water mass characteristics (temperature, salinity, and dissolved oxygen concentrations), collected during a ship-based campaign in the eastern Amundsen Sea in February–March 2014. Using a one-dimensional ocean model, processes such as variability in the characteristics of the source water masses on shelf and biological productivity/respiration are shown to affect the calculated apparent meltwater fractions. These processes can result in a false meltwater signature, creating misleading apparent glacial meltwater pathways. An alternative glacial meltwater calculation is suggested, using a pseudo–Circumpolar Deep Water endpoint and using an artificial increase in uncertainty of the dissolved oxygen measurements. The pseudo–Circumpolar Deep Water characteristics are affected by the under ice shelf bathymetry. The glacial meltwater fractions reveal a pathway for 2014 meltwater leading to the west of Pine Island Ice Shelf, along the coastline

NEDDylation is essential for Kaposi's sarcoma-associated herpesvirus latency and lytic reactivation and represents a novel anti-KSHV target.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL), which are aggressive malignancies associated with immunocompromised patients. For many non-viral malignancies, therapeutically targeting the ubiquitin proteasome system (UPS) has been successful. Likewise, laboratory studies have demonstrated that inhibition of the UPS might provide a promising avenue for the treatment of KSHV-associated diseases. The largest class of E3 ubiquitin ligases are the cullin-RING ligases (CRLs) that are activated by an additional ubiquitin-like protein, NEDD8. We show that pharmacological inhibition of NEDDylation (using the small molecule inhibitor MLN4924) is cytotoxic to PEL cells by inhibiting NF-κB. We also show that CRL4B is a novel regulator of latency as its inhibition reactivated lytic gene expression. Furthermore, we uncovered a requirement for NEDDylation during the reactivation of the KSHV lytic cycle. Intriguingly, inhibition prevented viral DNA replication but not lytic cycle-associated gene expression, highlighting a novel mechanism that uncouples these two features of KSHV biology. Mechanistically, we show that MLN4924 treatment precluded the recruitment of the viral pre-replication complex to the origin of lytic DNA replication (OriLyt). These new findings have revealed novel mechanisms that regulate KSHV latency and reactivation. Moreover, they demonstrate that inhibition of NEDDylation represents a novel approach for the treatment of KSHV-associated malignancies

Spin-ice physics in cadmium cyanide

Spin-ices are frustrated magnets that support a particularly rich variety of emergent physics. Typically, it is the interplay of magnetic dipole interactions, spin anisotropy, and geometric frustration on the pyrochlore lattice that drives spin-ice formation. The relevant physics occurs at temperatures commensurate with the magnetic interaction strength, which for most systems is 1–5 K. Here, we show that non-magnetic cadmium cyanide, Cd(CN)2, exhibits analogous behaviour to magnetic spin-ices, but does so on a temperature scale that is nearly two orders of magnitude greater. The electric dipole moments of cyanide ions in Cd(CN)2 assume the role of magnetic pseudospins, with the difference in energy scale reflecting the increased strength of electric vs magnetic dipolar interactions. As a result, spin-ice physics influences the structural behaviour of Cd(CN)2 even at room temperature.ISSN:2041-172