Comparative study on the in vitro and in vivo properties of two bovine herpesvirus-5 reference strains

<p>Abstract</p> <p>Background</p> <p>Bovine herpesvirus 5 (BoHV-5) is an alphaherpesvirus responsible for meningoencephalitis in young cattle and it is antigenically and genetically related to bovine herpesvirus 1. BoHV-5 outbreaks are sporadic and restricted in their geographical distribution, being mostly detected in the Southern hemisphere. The N569 and A663 strains are prototypes of the "a" and "b" subtypes of BoHV-5, however, scarce information about their <it>in vitro </it>and <it>in vivo </it>properties is currently available.</p> <p>Methods</p> <p>For the <it>in vitro </it>comparison between BoHV-5 A663 and N569 strains, viral growth kinetics, lysis and infection plaque size assays were performed. Additionally, an experimental infection of cattle with BoHV-5 A663 and N569 strains was carried out. Viral excretion, development of neurological signs, presence of specific antibodies in serum and nasal swabs and presence of latent BoHV-5 DNA in trigeminal ganglion, were analyzed. Histopathological examination of samples belonging to inoculated animals was also performed.</p> <p>Results</p> <p>The lytic capacity and the cell-to-cell spread was lower for the A663 strain compared to the N569 strain, however, the production of total infectious viral particles was similar between both strains. Concerning the <it>in vivo </it>properties, the A663 and N569 strains are able to induce similar degrees of pathogenicity in cattle.</p> <p>Conclusions</p> <p>Our results show that the A663 strain used in this study is less adapted to <it>in vitro </it>replication in MDBK cells than the N569 strain and, although slight differences were observed, both strains are able to induce a similar degree of virulence in the natural host.</p

In vitro-generated interspecific recombinants between bovine herpesviruses 1 and 5 show attenuated replication characteristics and establish latency in the natural host

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Gauge theories as a geometrical issue of a Kaluza-Klein framework

We present a geometrical unification theory in a Kaluza-Klein approach that achieve the geometrization of a generic gauge theory bosonic component. We show how it is possible to derive the gauge charge conservation from the invariance of the model under extra-dimensional translations and to geometrize gauge connections for spinors, thus we can introduce the matter just by free spinorial fields. Then, we present the applications to i)a pentadimensional manifold $V^{4}\otimes S^{1}$, so reproducing the original Kaluza-Klein theory, unless some extensions related to the rule of the scalar field contained in the metric and the introduction of matter by spinors with a phase dependence from the fifth coordinate, ii)a seven-dimensional manifold $V^{4}\otimes S^{1}\otimes S^{2}$, in which we geometrize the electro-weak model by introducing two spinors for any leptonic family and quark generation and a scalar field with two components with opposite hypercharge, responsible of spontaneous symmetry breaking.Comment: 37 pages, no figure

Research and management challenges following soil and landscape decontamination at the onset of the reopening of the Difficult-to-Return Zone, Fukushima (Japan)

Twelve years after the nuclear accident that occurred at the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) in March 2011, radiocesium contamination (with a large dominance of 137Cs, with a 30-year half-life) remains a major concern in various municipalities of north-eastern Japan. The Japanese authorities completed an unprecedented soil decontamination programme in residential and cultivated areas affected by the main radioactive plume (8953 km2). They implemented a complex remediation programme scheme to remediate soils that are fundamental to life on Earth, relying on different decision rules depending on the waste type, its contamination level and its region of origin, after delineating different zones exposed to contrasted radiation rates. The central objective was not to expose local inhabitants to radioactive doses exceeding 1 mSv yr−1 in addition to the natural levels. At the onset of the full reopening of the Difficult-to-Return Zone (DTRZ) in spring 2023, the current review provides an update of a previous synthesis published in 2019 (Evrard et al., 2019). Although this ambitious soil remediation and reconstruction programme has almost been completed in the 12 municipalities of Fukushima Prefecture in which an evacuation order was imposed in at least one neighbourhood in 2011, from the 147 443 inhabitants who lived there before the accident, only 29.9 % of them had returned by 2020. Waste generated by decontamination and tsunami cleaning/demolition work is planned to have been fully transported to (interim) storage facilities by the end of 2023. The cost of the operations conducted between 2011 and 2020 for the so-called “nuclear recovery” operations (including decontamination) was estimated by the Board of Audit of Japan in 2023 as JPY 6122.3 billion (∼ EUR 44 billion). Decontamination of cropland was shown to have impacted soil fertility, and potassium fertilisation is recommended to limit the transfer of residual radiocesium to new crops. In forests that cover 71 % of the surface area of Fukushima Prefecture and that were not targeted by remediation, radiocesium is now found in the upper mineral layer of the soil in a quasi-equilibrium state. Nevertheless, 137Cs concentrations in forest products (including wood for heating and construction, wild plants, wildlife game, mushrooms) often keep exceeding the threshold values authorised in Japan, which prohibits their exploitation in the area affected by the main plume. Radionuclides from forests were shown to be exported in dissolved and particle-bound forms to downstream river systems and floodplains, although multiple monitoring records showed the continuous decrease in radiocesium concentrations in both river water and sediment across the main plume between 2011 and 2021. Fish contamination is now generally found to be below the threshold limits although reputational damage remains a major concern for local fishing communities. The remobilisation of radiocesium from sediment accumulated in reservoirs of the region is also of potential concern as it may lead to secondary contamination of fish or irrigation waters supplied to decontaminated fields. Overall, this synthesis demonstrates the need to continue monitoring post-accidental radiocesium transfer in these environments and to keep sharing data in order to refine our predictive understanding of radiocesium mobility and consolidate the tools available to model contaminant transfer in ecosystems. In forests in particular, novel countermeasures and wood uses remain to be developed and tested. Furthermore, the hydrologic connectivity between soils under different ecosystems greatly influences long-term radiocesium transport. The consequences of extreme phenomena (e.g. typhoons, forest fires) that may become more frequent in the future as a result of global change in these contaminated environments should be further anticipated.</p

Kaluza-Klein and Gauss-Bonnet cosmic strings

We make a systematic investigation of stationary cylindrically symmetric solutions to the five-dimensional Einstein and Einstein-Gauss-Bonnet equations. Apart from the five-dimensional neutral cosmic string metric, we find two new exact solutions which qualify as cosmic strings, one corresponding to an electrically charged cosmic string, the other to an extended superconducting cosmic string surrounding a charged core. In both cases, test particles are deflected away from the singular line source. We extend both kinds of solutions to exact multi-cosmic string solutions.Comment: 26 pages, LaTex, no figure

Characterization of BoHV-5 field strains circulation and report of transient specific subtype of bovine herpesvirus 5 in Argentina

<p>Abstract</p> <p>Background</p> <p>Bovine herpesvirus 5 (BoHV-5) is a member of the subfamily <it>Alphaherpesvirinae </it>responsible for meningo-encephalitis in young cattle. The first case of bovine meningo-encephalitis associated with a herpesvirus infection was reported in Australia. The current geographical distribution of BoHV-5 infection is mainly restricted to South America, especially Brazil and Argentina. Outbreaks of BoHV-5 are regularly observed in Argentina suggesting the circulation of the virus in the bovine population.</p> <p>Results</p> <p>Seventeen field strains of BoHV-5 isolated from 1984 to now were confirmed by differential PCR and subjected to restriction endonuclease analysis (REA). Viral DNA was cleaved with BstEII which allows the differentiation among subtypes a, b and non a, non b. According to the REA with BstEII, only one field strain showed a pattern similar to the Argentinean A663 strain (prototype of BoHV-5b). All other isolates showed a clear pattern similar to the Australian N569 strain (prototype of BoHV-5a) consistent with the subtypes observed in Brazil, the other South-American country where BoHV-5 is known to be prevalent. The genomic region of subtype b responsible for the distinct pattern was determined and amplified by PCR; specifically a point mutation was identified in glycoprotein B gene, on the BstEII restriction site, which generates the profile specific of BoHV-5b.</p> <p>Conclusions</p> <p>This is the first report of circulation of BoHV-5a in Argentina as the prevailing subtype. Therefore the circulation of BoHV-5b was restricted to a few years in Argentina, speculating that this subtype was not able to be maintained in the bovine population. The mutation in the gB gene is associated with the difference in the restriction patterns between subtypes "a" and "b".</p

Solutions of multigravity theories and discretized brane worlds

We determine solutions to 5D Einstein gravity with a discrete fifth dimension. The properties of the solutions depend on the discretization scheme we use and some of them have no continuum counterpart. In particular, we find that the neglect of the lapse field (along the discretized direction) gives rise to Randall-Sundrum type metric with a negative tension brane. However, no brane source is required. We show that this result is robust under changes in the discretization scheme. The inclusion of the lapse field gives rise to solutions whose continuum limit is gauge fixed by the discretization scheme. We find however one particular scheme which leads to an undetermined lapse reflecting the reparametrization invariance of the continuum theory. We also find other solutions, with no continuum counterpart with changes in the metric signature or avoidance of singularity. We show that the models allow a continuous mass spectrum for the gravitons with an effective 4D interaction at small scales. We also discuss some cosmological solutions.Comment: 19 page

Boundary Terms and Junction Conditions for Generalized Scalar-Tensor Theories

We compute the boundary terms and junction conditions for Horndeski's panoptic class of scalar-tensor theories, and write the bulk and boundary equations of motion in explicitly second order form. We consider a number of special subclasses, including galileon theories, and present the corresponding formulae. Our analysis opens up of the possibility of studying tunnelling between vacua in generalized scalar-tensor theories, and braneworld dynamics. The latter follows because our results are independent of spacetime dimension.Comment: 13 pages, Equation corrected. Thanks to Tsutomu Kobayashi for informing us of the typ

Optimization of a Novel Peptide Ligand Targeting Human Carbonic Anhydrase IX

BACKGROUND: Carbonic anhydrase IX (CA IX) is a hypoxia-regulated transmembrane protein over-expressed in various types of human cancer. Recently, a new peptide with affinity for human carbonic anhydrase IX (CaIX-P1) was identified using the phage display technology. Aim of the present study is to characterize the binding site in the sequence of CaIX-P1, in order to optimize the binding and metabolic properties and use it for targeting purposes. METHODOLOGY/PRINCIPAL FINDINGS: Various fragments of CaIX-P1 were synthesized on solid support using Fmoc chemistry. Alanine scanning was performed for identification of the amino acids crucial for target binding. Derivatives with increased binding affinity were radiolabeled and in vitro studies were carried out on the CA IX positive human renal cell carcinoma cell line SKRC 52 and the CA IX negative human pancreatic carcinoma cell line BxPC3. Metabolic stability was investigated in cell culture medium and human serum. Organ distribution and planar scintigraphy studies were performed in Balb/c nu/nu mice carrying subcutaneously transplanted SKRC 52 tumors. The results of our studies clearly identified amino acids that are important for target binding. Among various fragments and derivatives the ligand CaIX-P1-4-10 (NHVPLSPy) was found to possess increased binding potential in SKRC 52 cells, whereas no binding capacity for BxPC3 cells was observed. Binding of radiolabeled CaIX-P1-4-10 on CA IX positive cells could be inhibited by both the unlabeled and the native CaIX-P1 peptide but not by control peptides. Stability experiments indicated the degradation site in the sequence of CaIX-P1-4-10. Biodistribution studies showed a higher in vivo accumulation in the tumor than in most healthy tissues. CONCLUSIONS: Our data reveal modifications in the sequence of the CA IX affine ligand CaIX-P1 that might be favorable for improvement of target affinity and metabolic stability, which are necessary prior to the use of the ligand in clinical approaches