Malignant Catarrhal Fever Induced by Alcelaphine herpesvirus 1 Is Associated with Proliferation of CD8+ T Cells Supporting a Latent Infection

Alcelaphine herpesvirus 1 (AlHV-1), carried by wildebeest asymptomatically, causes malignant catarrhal fever (WD-MCF) when cross-species transmitted to a variety of susceptible species of the Artiodactyla order. Experimentally, WD-MCF can be induced in rabbits. The lesions observed are very similar to those described in natural host species. Here, we used the rabbit model and in vivo 5-Bromo-2′-Deoxyuridine (BrdU) incorporation to study WD-MCF pathogenesis. The results obtained can be summarized as follows. (i) AlHV-1 infection induces CD8+ T cell proliferation detectable as early as 15 days post-inoculation. (ii) While the viral load in peripheral blood mononuclear cells remains below the detection level during most of the incubation period, it increases drastically few days before death. At that time, at least 10% of CD8+ cells carry the viral genome; while CD11b+, IgM+ and CD4+ cells do not. (iii) RT-PCR analyses of mononuclear cells isolated from the spleen and the popliteal lymph node of infected rabbits revealed no expression of ORF25 and ORF9, low or no expression of ORF50, and high or no expression of ORF73. Based on these data, we propose a new model for the pathogenesis of WD-MCF. This model relies on proliferation of infected CD8+ cells supporting a predominantly latent infection

Clinical performance and Willingness To Pay for soft toric contact lenses in low and moderate astigmats

Purpose: To determine clinical performance and the ‘Willingness To Pay’ for toric vs. spherical soft contact lenses in an astigmatic population. Methods: In the clinical study, subjects with binocular low to moderate astigmatism (-0.75DC to − 1.50DC) wore pairs of soft toric (Biofinity toric) and spherical (Biofinity) contact lenses in random sequence. Visual acuity (high and low contrast, monocular and binocular), subjective comfort and subjective vision were recorded. In the economics study, first subjects who had participated in the clinical study were presented with a series of randomised economic scenarios in order to determine their Willingness To Pay a premium (i.e. an increase) for toric lenses. Then, a similar set of scenarios were presented to a much larger group of online respondents and again, Willingness To Pay was established. Results: For the four measures of visual acuity, the Biofinity toric lens out-performed the Biofinity spherical lens by 0.6 to 1.1 lines.. Subjective vision performance was statistically significantly better with the toric lens for the distance task only. Comfort scores were not significantly different. Similar findings for Willingness To Pay were established for the clinical subjects and for the online respondents. The Willingness To Pay premium (additional fee) for a monthly supply of toric lenses (over spherical lenses) was between £13 and £16, if a toric lens provides better vision and similar comfort, as shown in the clinical study. Conclusion: Consumers are willing to pay a monthly premium of around 50% to benefit from the typical experience of better vision and similar comfort for toric vs. spherical lenses. The level of additional cost for toric lenses compared to their spherical equivalents is less than this in the market, so eye care professionals should consider that toric lenses are delivering a greater clinical return than anticipated by wearers for the relatively small increase in price

Novel Hendra Virus Variant Detected by Sentinel Surveillance of Horses in Australia

We identified and isolated a novel Hendra virus (HeV) variant not detected by routine testing from a horse in Queensland, Australia, that died from acute illness with signs consistent with HeV infection. Using whole-genome sequencing and phylogenetic analysis, we determined the variant had ≈83% nt identity with prototypic HeV. In silico and in vitro comparisons of the receptor-binding protein with prototypic HeV support that the human monoclonal antibody m102.4 used for postexposure prophylaxis and current equine vaccine will be effective against this variant. An updated quantitative PCR developed for routine surveillance resulted in subsequent case detection. Genetic sequence consistency with virus detected in grey-headed flying foxes suggests the variant circulates at least among this species. Studies are needed to determine infection kinetics, pathogenicity, reservoir-species associations, viral-host coevolution, and spillover dynamics for this virus. Surveillance and biosecurity practices should be updated to acknowledge HeV spillover risk across all regions frequented by flying foxes. © 2022 Centers for Disease Control and Prevention (CDC). All rights reserved

Novel Hendra Virus Variant Detected by Sentinel Surveillance of Horses in Australia

We identified and isolated a novel Hendra virus (HeV) variant not detected by routine testing from a horse in Queensland, Australia, that died from acute illness with signs consistent with HeV infection. Using whole-genome sequencing and phylogenetic analysis, we determined the variant had ≈83% nt identity with prototypic HeV. In silico and in vitro comparisons of the receptor-binding protein with prototypic HeV support that the human monoclonal antibody m102.4 used for postexposure prophylaxis and current equine vaccine will be effective against this variant. An updated quantitative PCR developed for routine surveillance resulted in subsequent case detection. Genetic sequence consistency with virus detected in grey-headed flying foxes suggests the variant circulates at least among this species. Studies are needed to determine infection kinetics, pathogenicity, reservoir-species associations, viral-host coevolution, and spillover dynamics for this virus. Surveillance and biosecurity practices should be updated to acknowledge HeV spillover risk across all regions frequented by flying foxes. © 2022 Centers for Disease Control and Prevention (CDC). All rights reserved

Establishing the health and wellbeing needs of mining host community in Brazil, Chile and Peru: a mixed-method approach to identify priority areas for action to help communities meet their SDG3 targets

Background The global mining industry is an important partner in advancing the 2030 Agenda for Sustainable Development. In 2018, Anglo American plc published their Sustainable Mining Plan, containing a goal for improving health and wellbeing aligned with the Sustainable Development Goal 3 (SDG3) targets. Having formed an independent multidisciplinary research consortium, we designed and implemented a mixed-methods approach to attain a deeper understanding of SDG3 priorities within the local context of communities hosting Anglo American mining operations located in Latin America. Methods In 2019, within the host communities of three mining operations in Chile, three in Brazil, and one in Peru, we conducted a qualitative study which included stakeholder workshops and key informant interviews. We also quantitatively appraised existing health data. Findings emerging from the qualitative and quantitative assessments were compared to identify health and wellbeing priority areas for action relevant to each community. Results Across the three countries, 120 people took part in workshops and 35 in interviews. In these workshops and interviews, non-communicable diseases (SDG3.4), harmful alcohol consumption (SDG3.5), and pollution, particularly air pollution (SDG3.9), were consistently identified as areas for priority action. There were similarities in the reporting of individual, interpersonal, community, societal, and structural factors underlying these priority areas across the different communities. The availability of quantitative data was generally good at the state level, becoming increasing sparse as we focused on smaller geographies. The priorities identified in the quantitative assessments generally aligned with those highlighted in the qualitative data. Conclusions We highlight the importance of engaging with local populations to understand and address health needs. To address the priorities identified, intervention packages tailored to the specific needs of host communities, that tackle associated upstream societal level factors, are required. To facilitate this, appropriate monitoring systems and epidemiological investigations should be implemented to better understand the local context and quantify health issues. In the host communities, it is essential for the mining sector to be a key health partner in promoting integrated programmes that contribute to achieving the priority objectives and targets aligned with the SDG3 agenda

Habitat and forage associations of a naturally colonising insect pollinator, the Tree Bumblebee Bombus hypnorum

Bumblebees (Bombus species) are major pollinators of commercial crops and wildflowers but factors affecting their abundance, including causes of recent population declines, remain unclear. Investigating the ecology of species with expanding ranges provides a potentially powerful means of elucidating these factors. Such species may also bring novel pollination services to their new ranges. We therefore investigated landscape-scale habitat use and foraging preferences of the Tree Bumblebee, B. hypnorum, a recent natural colonist that has rapidly expanded its range in the UK over the past decade. Counts of B. hypnorum and six other Bombus species were made in March-June 2012 within a mixed landscape in south-eastern Norfolk, UK. The extent of different landscape elements around each transect was quantified at three scales (250 m, 500 m and 1500 m). We then identified the landscape elements that best predicted the density of B. hypnorum and other Bombus species. At the best fitting scale (250 m), B. hypnorum density was significantly positively associated with extent of both urban and woodland cover and significantly negatively associated with extent of oilseed rape cover. This combination of landscape predictors was unique to B. hypnorum. Urban and woodland cover were associated with B. hypnorum density at three and two, respectively, of the three scales studied. Relative to other Bombus species, B. hypnorum exhibited a significantly higher foraging preference for two flowering trees, Crataegus monogyna and Prunus spinosa, and significantly lower preferences for Brassica napus, Glechoma hederacea and Lamium album. Our study provides novel, quantitative support for an association of B. hypnorum with urban and woodland landscape elements. Range expansion in B. hypnorum appears to depend, on exploitation of widespread habitats underutilised by native Bombus species, suggesting B. hypnorum will readily co-exist with these species. These findings suggest that management could target bumblebee species with distinctive habitat requirements to help maintain pollination service

HOX transcription factors are potential therapeutic targets in non-small-cell lung cancer (targeting HOX genes in lung cancer)

The HOX genes are a family of homeodomain-containing transcription factors that determine the identity of cells and tissues during embryonic development. They are also known to behave as oncogenes in some haematological malignancies. In this study, we show that the expression of many of the HOX genes is highly elevated in primary non-small-cell lung cancers (NSCLCs) and in the derived cell lines A549 and H23. Furthermore, blocking the activity of HOX proteins by interfering with their binding to the PBX co-factor causes these cells to undergo apoptosis in vitro and reduces the growth of A549 tumours in vivo. These findings suggest that the interaction between HOX and PBX proteins is a potential therapeutic target in NSCLC

FGFR3IIIS: a novel soluble FGFR3 spliced variant that modulates growth is frequently expressed in tumour cells

Fibroblast growth factor receptor 3 (FGFR3) is one of four high-affinity tyrosine kinase receptors for the FGF family of ligands, frequently associated with growth arrest and induction of differentiation. The extracellular immunoglobulin (IgG)-like domains II and III are responsible for ligand binding; alternative usage of exons IIIb and IIIc of the Ig-like domain III determining the ligand-binding specificity of the receptor. By reverse transcriptase polymerase chain reaction (RT–PCR) a novel FGFR3IIIc variant FGFR3IIIS, expressed in a high proportion of tumours and tumour cell lines but rarely in normal tissues, has been identified. Unlike recently described nonsense transcripts of FGFR3, the coding region of FGFR3IIIS remains in-frame producing a novel protein. The protein product is coexpressed with FGFR3IIIc in the membrane and soluble cell fractions; expression in the soluble fraction is decreased after exposure to bFGF but not aFGF. Knockout of FGFR3IIIS using antisense has a growth-inhibitory effect in vitro, suggesting a dominant-negative function for FGFR3IIIS inhibiting FGFR3-induced growth arrest. In summary, alternative splicing of the FGFR3 Ig-domain III represents a mechanism for the generation of receptor diversity. FGFR3IIIS may regulate FGF and FGFR trafficking and function, possibly contributing to the development of a malignant phenotype

Quantitative importance of staminodes for female reproductive success in Parnassia palustris under contrasting environmental conditions.

The five sterile stamens, or staminodes, in Parnassia palustris act both as false and as true nectaries. They attract pollinators with their conspicuous, but non-rewarding tips, and also produce nectar at the base. We removed staminodes experimentally and compared pollinator visitation rate and duration and seed set in flowers with and without staminodes in two different populations. We also examined the relative importance of the staminode size to other plant traits. Finally, we bagged, emasculated, and supplementary cross-pollinated flowers to determine the pollination strategy and whether reproduction was limited by pollen availability. Flowers in both populations were highly dependent on pollinator visitation for maximum seed set. In one population pollinators primarily cross-pollinated flowers, whereas in the other the pollinators facilitated self-pollination. The staminodes caused increased pollinator visitation rate and duration to flowers in both populations. The staminodes increased female reproductive success, but only when pollen availability constrained female reproduction. Simple linear regression indicated a strong selection on staminode size, multiple regression suggested that selection on staminode size was mainly caused by correlation with other traits that affected female fitness. [ABSTRACT FROM AUTHOR