Construction and testing of a novel host-range defective myxoma virus vaccine with the M063 gene inactivated that is non-permissive for replication in rabbit cells

Deletion of the M063 gene from myxoma virus produces a virus that is unable to replicate in rabbit cells in vitro or in live rabbits but can be propagated in non-rabbit cell lines. A targeted M063 deletion mutant was constructed in the attenuated Uriarra strain of myxoma virus and the ability of this virus to act as a safe, non-transmissible vaccine against myxomatosis was tested in outbred laboratory rabbits. Immunization with the M063 deletion vaccine provided good short-term protection against lethal challenge with virulent myxoma virus. Long-term protection was similar to reported results with heterologous live virus, with some rabbits protected but others succumbing to challenge. Replication-deficient poxvirus vaccines, like the Modified Vaccinia Virus Ankara (MVA) in man and the myxoma virus vaccine described here in rabbits, are very attractive from a safety perspective. Seasonal boosting would be predicted to provide long-term protection. Targeted host-range gene deletions could have potential for rapid development of poxvirus vaccines in general.This study was funded by the Pest Animal Control Cooperative Research Centre. Grant McFadden is an International Scholar of the Howard Hughes Medical Institute

Field testing a novel high residence positioning system for monitoring the fine‐scale movements of aquatic organisms

1. Acoustic telemetry is an important tool for studying the behaviour of aquatic organisms in the wild. 2. VEMCO high residence (HR) tags and receivers are a recent introduction in the field of acoustic telemetry and can be paired with existing algorithms (e.g. VEMCO positioning system [VPS]) to obtain high‐resolution two‐dimensional positioning data. 3. Here, we present results of the first documented field test of a VPS composed of HR receivers (hereafter, HR‐VPS). We performed a series of stationary and moving trials with HR tags (mean HR transmission period = 1.5 s) to evaluate the precision, accuracy and temporal capabilities of this positioning technology. In addition, we present a sample of data obtained for five European perch Perca fluviatilis implanted with HR tags (mean HR transmission period = 4 s) to illustrate how this technology can estimate the fine‐scale behaviour of aquatic animals. 4. Accuracy and precision estimates (median [5th–95th percentile]) of HR‐VPS positions for all stationary trials were 5.6 m (4.2–10.8 m) and 0.1 m (0.02–0.07 m), respectively, and depended on the location of tags within the receiver array. In moving tests, tracks generated by HR‐VPS closely mimicked those produced by a handheld GPS held over the tag, but these differed in location by an average of ≈9 m. 5. We found that estimates of animal speed and distance travelled for perch declined when positional data for acoustically tagged perch were thinned to mimic longer transmission periods. These data also revealed a trade‐off between capturing real nonlinear animal movements and the inclusion of positioning error. 6. Our results suggested that HR‐VPS can provide more representative estimates of movement metrics and offer an advancement for studying fine‐scale movements of aquatic organisms, but high‐precision survey techniques may be needed to test these systems

Helping Made Easy: Ease of Argument Generation Enhances Intentions to Help

Previous work has shown that self-generating arguments is more persuasive than reading arguments provided by others, particularly if self-generation feels easy. The present study replicates and extends these findings by providing evidence for fluency effects on behavioral intention in the realm of helping. In two studies, participants were instructed to either self-generate or read two versus ten arguments about why it is good to help. Subsequently, a confederate asked them for help. Results show that self-generating few arguments is more effective than generating many arguments. While this pattern reverses for reading arguments, easy self-generation is the most effective strategy compared to all other conditions. These results have important implications for fostering behavioral change in all areas of life

A reversion of an IL2RG mutation in combined immunodeficiency providing competitive advantage to the majority of CD8+ T cells

Mutations in the common gamma chain (γc, CD132, encoded by the IL2RG gene) can lead to B+T-NK-X-linked severe combined immunodeficiency, as a consequence of unresponsiveness to γc-cytokines such as interleukins-2, -7 and -15. Hypomorphic mutations in CD132 may cause combined immunodeficiencies with a variety of clinical presentations. We analyzed peripheral blood mononuclear cells of a 6-year-old boy with normal lymphocyte counts, who suffered from recurrent pneumonia and disseminated mollusca contagiosa. Since proliferative responses of T cells and NK cells to γc -cytokines were severely impaired, we performed IL2RG gene analysis, showing a heterozygous mutation in the presence of a single X-chromosome. Interestingly, an IL2RG reversion to normal predominated in both naïve and antigen-primed CD8+ T cells and increased over time. Only the revertant CD8+T cells showed normal expression of CD132 and the various CD8+T cell populations had a different T-cell receptor repertoire. Finally, a fraction of γδ+T cells and differentiated CD4+CD27-effector-memory T cells carried the reversion, whereas NK or B cells were repeatedly negative. In conclusion, in a patient with a novel IL2RG mutation, gene-reverted CD8+T cells accumulated over time. Our data indicate that selective outgrowth of particular T-cell subsets may occur following reversion at the level of committed T progenitor cells

Application of CO2 laser evaporation in locally advanced melanoma

Aim: This study aims to investigate the role of CO(2)laser evaporation in the treatment of melanoma patients with satellite or in-transit metastases. Materials & methods: Patients who underwent CO2 laser evaporation were retrospectively included between November 2002 and August 2018. The Sharplan 40C CO2 laser was used with a high pulse wave mode. Data concerning patient and tumor characteristics, CO2 laser evaporation and subsequent therapies were collected. Results:A total of 26patients were included. Median duration of local control was 5.5 months. The median number of lesions evaporated per treatment was three (1-16); patients received a median of three (1-19) treatments. Conclusion: In a selected group of melanoma patients with satellite or in-transit metastases, CO2 laser evaporation should be considered as treatment for local control

Enhancement of the magnetic anisotropy of nanometer-sized Co clusters: influence of the surface and of the inter-particle interactions

We study the magnetic properties of spherical Co clusters with diameters between 0.8 nm and 5.4 nm (25 to 7500$ atoms) prepared by sequential sputtering of Co and Al2O3. The particle size distribution has been determined from the equilibrium susceptibility and magnetization data and it is compared to previous structural characterizations. The distribution of activation energies was independently obtained from a scaling plot of the ac susceptibility. Combining these two distributions we have accurately determined the effective anisotropy constant Keff. We find that Keff is enhanced with respect to the bulk value and that it is dominated by a strong anisotropy induced at the surface of the clusters. Interactions between the magnetic moments of adjacent layers are shown to increase the effective activation energy barrier for the reversal of the magnetic moments. Finally, this reversal is shown to proceed classically down to the lowest temperature investigated (1.8 K).Comment: 13 figures submitted to Phys. Rev.