De Novo synthesis of VP16 coordinates the exit from HSV latency in vivo

The mechanism controlling the exit from herpes simplex virus latency (HSV) is of central importance to recurrent disease and transmission of infection, yet interactions between host and viral functions that govern this process remain unclear. The cascade of HSV gene transcription is initiated by the multifunctional virion protein VP16, which is expressed late in the viral replication cycle. Currently, it is widely accepted that VP16 transactivating function is not involved in the exit from latency. Utilizing the mouse ocular model of HSV pathogenesis together with genetically engineered viral mutants and assays to quantify latency and the exit from latency at the single neuron level, we show that in vivo (i) the VP16 promoter confers distinct regulation critical for viral replication in the trigeminal ganglion (TG) during the acute phase of infection and (ii) the transactivation function of VP16 (VP16TF) is uniquely required for the exit from latency. TG neurons latently infected with the VP16TF mutant in 1814 do not express detectable viral proteins following stress, whereas viruses with mutations in the other major viral transcription regulators ICP0 and ICP4 do exit the latent state. Analysis of a VP16 promoter/reporter mutant in the background of in 1814 demonstrates that the VP16 promoter is activated in latently infected neurons following stress in the absence of other viral proteins. These findings support the novel hypothesis that de novo expression of VP16 regulates entry into the lytic program in neurons at all phases of the viral life cycle. HSV reactivation from latency conforms to a model in which stochastic derepression of the VP16 promoter and expression of VP16 initiates entry into the lytic cycl

Intensive beef production; accomplishments and problems

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Comparison of response surface methodology (RSM) and artificial neural networks (ANN) towards efficient extraction of artemisinin from Artemisia annua

The solid-liquid extraction of Artemisia annua remains an important source of artemisinin, the precursor molecule to the most potent anti-malarial drugs available. Industrial manufacturers of artemisinin face many challenges in regards to volatile markets and sub-optimal extraction approaches. There is a need to improve current processing conditions, and one method is to model the processing options and identify the most appropriate process conditions to suit the market forces. This study examined the impact of extraction temperature, duration and solvent (petroleum ether) to leaf proportions on the recovery of artemisinin from leaf steeped in solvent, in a central composite design (CCD), and the results were used to generate both a response surface methodology (RSM) model and an artificial neural network (ANN) model. Appraisal of the models through the coefficient of determination (R2) and the absolute average deviation (AAD) showed that the ANN was superior (R2 = 0.991, AAD = 1.37%) to the RSM model (R2 = 0.903, AAD = 4.57%) in predicting artemisinin recovery. The ANN model was subsequently used to determine the optimal extraction conditions for the recovery of artemisinin, which were found to be an extraction duration of 8 h at a temperature of 45 ◦C and a leaf loading of 0.12 g/ml petroleum ether, from the conditions tested. An illustration is provided in how the results obtained from an ANN model may be used to determine optimal extraction conditions in response to market conditions. In addition, a co-solvency effect has been observed between extracted impurities and petroleum ether that substantially increases the solubility of artemisinin over that in petroleum ether alone, and which will require further investigation in the future. The impact of this co-solvency effect on the efficiency of artemisinin recovery in secondary extraction cycles was found to be significant

Comparison of Coulomb Blockade Thermometers with the International Temperature Scale PLTS-2000

The operation of the primary Coulomb blockade thermometer (CBT) is based on a measurement of bias voltage dependent conductance of arrays of tunnel junctions between normal metal electrodes. Here we report on a comparison of a CBT with a high accuracy realization of the PLTS-2000 temperature scale in the range from 0.008 K to 0.65 K. An overall agreement of about 1% was found for temperatures above 0.25 K. For lower temperatures increasing differences are caused by thermalization problems which are accounted for by numerical calculations based on electron-phonon decoupling.Comment: 6 pages, 5 figure

Bedside theatre performance and its effects on hospitalised children's well-being

This article reports on practice-based pilot research being undertaken at Birmingham Children's Hospital in England on the impact of bedside theatre performance on hospitalised children's well-being. It discusses the process of creating theatre for sick children, connecting with the hospital and working within the hospital tight routines, dealing with ethics, working with theatre artists and performing to children bedside. It also reports on evidence collected by questionnaire and interviews about the perceived benefits of bedside theatre by children and their parent/carers. This emphasis on the process is appropriate for theatre practitioners, arts therapists and clinical staff who work with hospitalised children

On Quantum Markov Chains on Cayley tree II: Phase transitions for the associated chain with XY-model on the Cayley tree of order three

In the present paper we study forward Quantum Markov Chains (QMC) defined on a Cayley tree. Using the tree structure of graphs, we give a construction of quantum Markov chains on a Cayley tree. By means of such constructions we prove the existence of a phase transition for the XY-model on a Cayley tree of order three in QMC scheme. By the phase transition we mean the existence of two now quasi equivalent QMC for the given family of interaction operators $\{K_{}\}$.Comment: 34 pages, 1 figur

Chasing the genes that control resistance to gastrointestinal nematodes

The host-protective immune response to infection with gastrointestinal (GI) nematodes involves a range of interacting processes that begin with recognition of the parasite’s antigens and culminate in an inflammatory reaction in the intestinal mucosa. Precisely which immune effectors are responsible for the loss of specific worms is still not known although many candidate effectors have beenproposed. However, it is now clear that many different genes regulate the response and that differences between hosts (fast or strong versus slow or weak responses) can be explained by allelic variation in crucial genes associated with the gene cascade that accompanies the immune response and/or genes encoding constitutively expressed receptor/signalling molecules. Major histocompatibility complex (MHC) genes have been recognized for some time as decisive in controlling immunity, and evidence that non-MHC genes are equally, if not more important in this respect has also been available for two decades. Nevertheless, whilst the former have been mapped in mice, only two candidate loci have been proposed for non-MHC genes and relatively little is known about their roles. Now, with the availability of microsatellite markers, it is possible to exploit linkage mapping techniques to identify quantitative trait loci (QTL) responsible for resistance to GI nematodes. Four QTL for resistance to Heligmosomoides polygyrus, and additional QTL affecting faecal egg production by the worms and the accompanying immune responses, have been identified. Fine mapping and eventually the identification of the genes (and their alleles) underlying QTL for resistance/susceptibility will permit informed searches for homologues in domestic animals, and human beings, through comparative genomic maps. This information in turn will facilitate targeted breeding to improve resistance in domestic animals and, in human beings, focused application of treatment and control strategies for GI nematodes

Approximate k-state solutions to the Dirac-Yukawa problem based on the spin and pseudospin symmetry

Using an approximation scheme to deal with the centrifugal (pseudo-centrifugal) term, we solve the Dirac equation with the screened Coulomb (Yukawa) potential for any arbitrary spin-orbit quantum number {\kappa}. Based on the spin and pseudospin symmetry, analytic bound state energy spectrum formulas and their corresponding upper- and lower-spinor components of two Dirac particles are obtained using a shortcut of the Nikiforov-Uvarov method. We find a wide range of permissible values for the spin symmetry constant C_{s} from the valence energy spectrum of particle and also for pseudospin symmetry constant C_{ps} from the hole energy spectrum of antiparticle. Further, we show that the present potential interaction becomes less (more) attractive for a long (short) range screening parameter {\alpha}. To remove the degeneracies in energy levels we consider the spin and pseudospin solution of Dirac equation for Yukawa potential plus a centrifugal-like term. A few special cases such as the exact spin (pseudospin) symmetry Dirac-Yukawa, the Yukawa plus centrifugal-like potentials, the limit when {\alpha} becomes zero (Coulomb potential field) and the non-relativistic limit of our solution are studied. The nonrelativistic solutions are compared with those obtained by other methods.Comment: 21 pages, 6 figure