A Selective Advantage for Conservative Viruses

In this letter we study the full semi-conservative treatment of a model for the co-evolution of a virus and an adaptive immune system. Regions of viability are calculated for both conservatively and semi-conservatively replicating viruses interacting with a realistic semi-conservatively replicating immune system. The conservative virus is found to have a selective advantage in the form of an ability to survive in regions with a wider range of mutation rates than its semi-conservative counterpart. This may help explain the existence of a rich range of viruses with conservatively replicating genomes, a trait which is found nowhere else in nature.Comment: 4 pages, 2 figure

Disruption of the UL41 gene in the herpes simplex virus 2 dl5-29 mutant increases its immunogenicity and protective capacity in a murine model of genital herpes

AbstractThe herpes simplex virus 2 dl5-29 replication-defective mutant virus has been shown to induce protective immunity in mice and both prophylactic and therapeutic immunity in guinea pigs. In an attempt to improve the efficacy of dl5-29 we disrupted its UL41 gene, producing the triple mutant virus dl5-29-41L. dl5-29-41L has a decreased ability to inhibit host cell protein synthesis and a reduced cytopathic effect on cultured cells. When used to immunize mice, dl5-29-41L elicited significantly stronger neutralizing antibody responses and significantly stronger CD4+ and CD8+ cellular immune responses than dl5-29. The enhanced immune responses corresponded with increased protective capacity in a murine model of genital herpes. The protective immunity elicited by either virus was very durable, protecting mice for at least 7 months. Furthermore, we show that cell lysate preparations of both viruses were significantly more efficacious than the corresponding extracellular virus preparations

Wild olive seed weevil, Anchonocranus oleae Marshall (Coleoptera: Curculionidae), in cultivated olives in South Africa

Wild olive seed weevil, Anchonocranus oleae Marshall, larvae as well as oviposition and feeding damage were recorded in cultivated olives during a recent study on olive seed wasps in South Africa. Prematurely dropped fruit and fruit picked at harvest in two orchards near Stellenbosch and Agter- Paarl were examined regularly for olive seed wasp infestation over three seasons. In addition, olives were collected over a wider area of the olive growing regions of the Western Cape province for a survey to determine olive seed wasp distribution. DNA barcoding confirmed the identity of weevil larvae in kernels as A. oleae. The number of A. oleae larvae found in olive seeds and the number of olives with weevil oviposition or feeding damage were low. The presence of larvae and weevil damage in two orchards in the survey with no wild olive trees in close proximity suggest that the weevil could breed and persist in cultivated olive orchards. Currently A. oleae is not of economic concern, but if infested olives are discarded at harvest and left in orchards, the weevils could complete their development in the kernels and numbers could increase to damaging levels

Attempted suicide in Sri Lanka –An epidemiological study of household and community factors

An individual's suicide risk is determined by personal characteristics, but is also influenced by their environment. Previous studies indicate a role of contextual effects on suicidal behaviour, but there is a dearth of quantitative evidence from Asia.Individual and community level data were collected on 165,233 people from 47,919 households in 171 communities in rural Sri Lanka. Data were collected on individual (age, sex, past suicide attempts and individual socioeconomic position (SEP)) and household (household SEP, pesticide access, alcohol use and multigenerational households) level factors. We used 3-level logit models to investigate compositional (individual) and contextual (household/community) effects.We found significant variation between households 21% (95% CI 18%, 24%) and communities 4% (95% CI 3%, 5%) in the risk of a suicide attempt. Contextual factors as measured by low household SEP (OR 2.37 95% CI 2.10, 2.67), low community SEP (OR 1.45 95% CI 1.21, 1.74), and community 'problem' alcohol use (OR 1.44 95% CI 1.19, 1.75) were associated with an increased risk of suicide attempt. Women living in households with alcohol misuse were at higher risk of attempted suicide. We observed a protective effect of living in multigenerational households (OR 0.53 95% CI 0.42, 0.65).The outcome was respondent-reported and refers to lifetime reports of attempted suicide, therefore this study might be affected by socially desirable responding.Our study finds that contextual factors are associated with an individual's risk of attempted suicide in Sri Lanka, independent of an individual's personal characteristics

Proteomics of herpes simplex virus infected cell protein 27: association with translation initiation factors

AbstractThe herpes simplex virus (HSV) immediate early ICP27 protein plays an essential role in stimulating viral early and late gene expression. ICP27 appears to be multifunctional in that it has been reported to stimulate viral late gene transcription, polyadenylation site usage, and RNA export. We report here on proteomic studies involving immunoprecipitation of ICP27 and mass spectrometric identification of co-precipitated proteins. These studies show an association of ICP27 with the cellular translation initiation factors poly A binding protein (PABP), eukaryotic initiation factor 3 (eIF3), and eukaryotic initiation factor 4G (eIF4G) in infected cells. Immunoprecipitation-western blot studies confirmed these associations. Finally, purified MBP-tagged ICP27 (MBP-27) can interact with eIF3 subunits p47 and p116 in vitro. These results suggest that ICP27 may also play a role in stimulating translation of certain viral and host mRNAs and/or in inhibiting host mRNA translation

Redox-dependent conformational switching of diphenylacetylenes

Herein we describe the design and synthesis of a redox-dependent single-molecule switch. Appending a ferrocene unit to a diphenylacetylene scaffold gives a redox-sensitive handle, which undergoes reversible one-electron oxidation, as demonstrated by cyclic voltammetry analysis. 1H-NMR spectroscopy of the partially oxidized switch and control compounds suggests that oxidation to the ferrocenium cation induces a change in hydrogen bonding interactions that results in a conformational switch

Salmonella Contamination of Swine Carcasses and Pork Products

This paper includes results from two separate studies: one surveyed the level of contamination at four points during the slaughter and processing of chilled pork; the second study surveyed ground pork from 17 companies representing five different segments of ground pork distribution. Regarding the carcass study, the highest percentage of Salmonella spp. isolated from the different sampling sites by a swab method, for both pork loin and ham surfaces, was 4.4% after the singeing step of the slaughter process. Overall, 1.7% of all pork samples showing positive isolations for Salmonella spp., however, there were no Salmonella spp. found in one of the three plants surveyed. Salmonella were isolated primarily from pork before fabrication and refrigerated storage. A continous reduction in the numbers of Salmonella spp. isolates was detected from the point of singeing to the point of fabrication. No Salmonella spp. were isolated from vacuumpackaged pork stored for 36 days at 2EC. The purpose of the ground pork project was to survey current sources of ground pork, and to determine the effects of different handling methods and raw material sources on the microbial quality of ground pork. There were no significant differences in the microbial counts, or prevalence of selected organisms, between the different types of companies from which the ground pork was obtained. Estimated variance among locations, samples and sample duplicates show that additional ground pork samples are needed to strengthen the results of this study

Evaluating deformation behavior of a TBC-System during thermal gradient mechanical fatigue by means of high energy X-ray diffraction

Applications of TBC-systems involve complex thermal mechanical loading pattern including transient thermal gradients across the coated system, which result in multiaxial stresses and stress gradients affecting the damage behavior. In an ongoing research, starting more than 10 years ago, the authors developed laboratory test facilities for evaluating the damage behavior of TBC-systems for gas turbine blades in aeroengines under realistic thermal mechanical loading conditions [1]. Fatigue tests involving thermal gradients have been conducted and damage behavior in dependence of load pattern and pre heat treatment has been intensively investigated on TBC-systems comprising a partially yttria stabilized zirconia (YSZ) topcoat and a MCrAlY bond coat both applied by electron physical vapor deposition (EB-PVD) onto nickel based super alloys serving as substrate [2]. Numerical analyses by means of FE-calculations did provide hypotheses explaining the observed damage behavior [3], but even though the results are plausible they did depend on reasonable assumptions on materials properties since reliable data on the properties of the thin coating layers are still lacking, especially for high temperatures. High energy X-ray diffraction can provide the requested information since it is possible to achieve information on the local deformation processes in each layer with high spatial resolution, and short acquisition times allow for in situ investigation of time dependent deformation processes. A new test facility based on concepts after [1] for cyclic thermal loading of tubular specimens and applying a controlled thermal gradient across the coated specimen’s wall has been developed for implementation into an electro-mechanical test machine at the advanced photon source (APS) at Argonne National Laboratory. A precision positioning rig allows for exact µm-positioning of the entire test machine with respect to the focused X-ray beam, and X-ray diffraction patterns were taken using a 2D detector, giving accurate 360° lattice parameter data [4]. Tests have been performed with varying thermal and mechanical load schemata intending to determine material properties from the respective strain response. The beam energy was 65 keV, and throughout all experiments the beam scanned through the coating layers with a window and step size of 30 µm. Strain data were acquired in plane parallel to the specimen’s length axis and out of plane. Results of the strain data evaluation will be presented and discussed. Exemplary results are: - Elastic properties of the YSZ showed a gradient across the coating thickness reflecting the microstructure gradient of the YSZ resulting from the EB-PVD process. - The YSZ strain was – below the deposition temperature - in plane compressive and out of plane tensile, which is a consequence of (i) the higher thermal expansion coefficient of YSZ with respect to the substrate and (ii) the cylindrical specimen geometry with the YSZ at the outer surface. [1] M. Bartsch, G. Marci, K. Mull, C. Sick, Adv. Eng. Mater. (1999), 1(2), 127–9 [2] M. Bartsch, B. Baufeld, S. Dalkilic, L. Chernova, M. Heinzelmann, Int. J. Fatigue (2008) 30, 211–8 [3] M. T. Hernandez, A. M. Karlsson, M. Bartsch, Surf. Coat. Technol. (2009) 203, 3549–58 [4] S.F. Siddiqui, K. Knipe, A. Manero, C. Meid, J. Wischek, J. Okasinski, J. Almer, A.M. Karlsson, M. Bartsch, S. Raghavan, Review of Scientific Instruments (2013) 84, 08390

Minority and mode conversion heating in (3He)-H JET plasma

Radio frequency (RF) heating experiments have recently been conducted in JET (He-3)-H plasmas. This type of plasmas will be used in ITER's non-activated operation phase. Whereas a companion paper in this same PPCF issue will discuss the RF heating scenario's at half the nominal magnetic field, this paper documents the heating performance in (He-3)-H plasmas at full field, with fundamental cyclotron heating of He-3 as the only possible ion heating scheme in view of the foreseen ITER antenna frequency bandwidth. Dominant electron heating with global heating efficiencies between 30% and 70% depending on the He-3 concentration were observed and mode conversion (MC) heating proved to be as efficient as He-3 minority heating. The unwanted presence of both He-4 and D in the discharges gave rise to 2 MC layers rather than a single one. This together with the fact that the location of the high-field side fast wave (FW) cutoff is a sensitive function of the parallel wave number and that one of the locations of the wave confluences critically depends on the He-3 concentration made the interpretation of the results, although more complex, very interesting: three regimes could be distinguished as a function of X[He-3]: (i) a regime at low concentration (X[He-3] < 1.8%) at which ion cyclotron resonance frequency (ICRF) heating is efficient, (ii) a regime at intermediate concentrations (1.8 < X[He-3] < 5%) in which the RF performance is degrading and ultimately becoming very poor, and finally (iii) a good heating regime at He-3 concentrations beyond 6%. In this latter regime, the heating efficiency did not critically depend on the actual concentration while at lower concentrations (X[He-3] < 4%) a bigger excursion in heating efficiency is observed and the estimates differ somewhat from shot to shot, also depending on whether local or global signals are chosen for the analysis. The different dynamics at the various concentrations can be traced back to the presence of 2 MC layers and their associated FW cutoffs residing inside the plasma at low He-3 concentration. One of these layers is approaching and crossing the low-field side plasma edge when 1.8 < X[He-3] < 5%. Adopting a minimization procedure to correlate the MC positions with the plasma composition reveals that the different behaviors observed are due to contamination of the plasma. Wave modeling not only supports this interpretation but also shows that moderate concentrations of D-like species significantly alter the overall wave behavior in He-3-H plasmas. Whereas numerical modeling yields quantitative information on the heating efficiency, analytical work gives a good description of the dominant underlying wave interaction physics

Differential cargo mobilisation within Weibel-Palade bodies after transient fusion with the plasma membrane.

Inflammatory chemokines can be selectively released from Weibel-Palade bodies (WPBs) during kiss-and-run exocytosis. Such selectivity may arise from molecular size filtering by the fusion pore, however differential intra-WPB cargo re-mobilisation following fusion-induced structural changes within the WPB may also contribute to this process. To determine whether WPB cargo molecules are differentially re-mobilised, we applied FRAP to residual post-fusion WPB structures formed after transient exocytosis in which some or all of the fluorescent cargo was retained. Transient fusion resulted in WPB collapse from a rod to a spheroid shape accompanied by substantial swelling (>2 times by surface area) and membrane mixing between the WPB and plasma membranes. Post-fusion WPBs supported cumulative WPB exocytosis. To quantify diffusion inside rounded organelles we developed a method of FRAP analysis based on image moments. FRAP analysis showed that von Willebrand factor-EGFP (VWF-EGFP) and the VWF-propolypeptide-EGFP (Pro-EGFP) were immobile in post-fusion WPBs. Because Eotaxin-3-EGFP and ssEGFP (small soluble cargo proteins) were largely depleted from post-fusion WPBs, we studied these molecules in cells preincubated in the weak base NH4Cl which caused WPB alkalinisation and rounding similar to that produced by plasma membrane fusion. In these cells we found a dramatic increase in mobilities of Eotaxin-3-EGFP and ssEGFP that exceeded the resolution of our method (∼ 2.4 µm2/s mean). In contrast, the membrane mobilities of EGFP-CD63 and EGFP-Rab27A in post-fusion WPBs were unchanged, while P-selectin-EGFP acquired mobility. Our data suggest that selective re-mobilisation of chemokines during transient fusion contributes to selective chemokine secretion during transient WPB exocytosis. Selective secretion provides a mechanism to regulate intravascular inflammatory processes with reduced risk of thrombosis