Canine plasma and tissue fatty acid profiles and their correlation with hair coat conditions

This study was initiated to study the probable relationships between the fatty acid profiles of the plasma, skin, liver and brain and to determine their correlations with hair coat conditions in owned and stray dogs. A total of35 dogs were used in this study. Twenty-three owned dogs obtained from the University Veterinary Hospital (UVH dogs) were subjected to blood sampling and hair coat scoring only. Twelve euthanized dogs were sourced from a local animal shelter (LAS dogs) and blood, brain, liver and skin samples were obtained. Hair coat scores were performed under standardized conditions and was found that the UVH dogs (median score = 4.1) had significantly better scores compared to LAS dogs (median score = 3.1, P<0.05). The UVH dogs had significantly lower (P<0.05) n-6:n-3 ratios and lower plasma arachidonate content. The skin and plasma fatty acid profiles correlated well with each other but no correlation was evident between the brain and plasma fatty acid profiles. Increased amounts of plasma and skin n-3 and n-6 polyunsaturated fatty acids were associated with better hair coat conditions. However, plasma n-6 fatty acids seemed to .have a stronger positive correlation to hair coat scores in dogs (p = 0.683, P<0.05) compared to plasma n-3 fatty acids (p = 0.512, P<0.05) and fatty acid profiles from other tissues. In summary, this report underscores the importance of n-3 and n-6 fatty acids to the hair coat condition of dogs kept under humid tropical conditions

SARS-CoV 9b protein diffuses into nucleus, undergoes active Crm1 mediated nucleocytoplasmic export and triggers apoptosis when retained in the nucleus

10.1371/journal.pone.0019436PLoS ONE65

The future of social care funding: who pays?

With the UK population ageing, deciding upon a satisfactory and sustainable system for the funding of people’s long-term care (LTC) needs has long been a topic of political debate. Phase 1 of the Care Act 2014 (“the Act”) brought in some of the reforms recommended by the Dilnot Commission in 2011. However, the Government announced during 2015 that Phase 2 of “the Act” such as the introduction of a £72,000 cap on Local Authority care costs and a change in the means testing thresholds 1 would be deferred until 2020. In addition to this delay, the “freedom and choice” agenda for pensions has come into force. It is therefore timely that the potential market responses to help people pay for their care within the new pensions environment should be considered. In this paper, we analyse whether the proposed reforms meet the policy intention of protecting people from catastrophic care costs, whilst facilitating individual understanding of their potential care funding requirements. In particular, we review a number of financial products and ascertain the extent to which such products might help individuals to fund the LTC costs for which they would be responsible for meeting. We also produce case studies to demonstrate the complexities of the care funding system. Finally, we review the potential impact on incentives for individuals to save for care costs under the proposed new means testing thresholds and compare these with the current thresholds. We conclude that: ∙ Although it is still too early to understand exactly how individuals will respond to the pensions freedom and choice agenda, there are a number of financial products that might complement the new flexibilities and help people make provision for care costs. ∙ The new care funding system is complex making it difficult for people to understand their potential care costs. ∙ The current means testing system causes a disincentive to save. The new means testing thresholds provide a greater level of reward for savers than the existing thresholds and therefore may increase the level of saving for care; however, the new thresholds could still act as a barrier since disincentives still exist

Development of polymer-assisted nanoparticles and nanogels for cancer therapy: an update

With cancer remaining as one of the main causes of deaths worldwide, many studies are undergoing the effort to look for a novel and potent anticancer drug. Nanoparticles (NPs) are one of the rising fields in research for anticancer drug development. One of the key advantages of using NPs for cancer therapy is its high flexibility for modification, hence additional properties can be added to the NPs in order to improve its anticancer action. Polymer has attracted considerable attention to be used as a material to enhance the bioactivity of the NPs. Nanogels, which are NPs cross-linked with hydrophilic polymer network have also exhibited benefits in anticancer application. The characteristics of these nanomaterials include non-toxic, environment-friendly, and variable physiochemical properties. Some other unique properties of polymers are also attributed by diverse methods of polymer synthesis. This then contributes to the unique properties of the nanodrugs. This review article provides an in-depth update on the development of polymer-assisted NPs and nanogels for cancer therapy. Topics such as the synthesis, usage, and properties of the nanomaterials are discussed along with their mechanisms and functions in anticancer application. The advantages and limitations are also discussed in this article

SARS-CoV-2 receptor binding domain displayed on HBsAg virus–like particles elicits protective immunity in macaques

Authorized vaccines against SARS-CoV-2 remain less available in low- and middle-income countries due to insufficient supply, high costs, and storage requirements. Global immunity could still benefit from new vaccines using widely available, safe adjuvants, such as alum and protein subunits, suited to low-cost production in existing manufacturing facilities. Here, a clinical-stage vaccine candidate comprising a SARS-CoV-2 receptor binding domain–hepatitis B surface antigen virus–like particle elicited protective immunity in cynomolgus macaques. Titers of neutralizing antibodies (>104) induced by this candidate were above the range of protection for other licensed vaccines in nonhuman primates. Including CpG 1018 did not significantly improve the immunological responses. Vaccinated animals challenged with SARS-CoV-2 showed reduced median viral loads in bronchoalveolar lavage (~3.4 log10) and nasal mucosa (~2.9 log10) versus sham controls. These data support the potential benefit of this design for a low-cost modular vaccine platform for SARS-CoV-2 and other variants of concern or betacoronaviruses

Identification of simple sequence repeat markers for sweetpotato weevil resistance

The development of sweetpotato [Ipomoea batatas (L.) Lam] germplasm with resistance to sweetpotato weevil (SPW) requires an understanding of the biochemical and genetic mechanisms of resistance to optimize crop resistance. The African sweetpotato landrace, ‘New Kawogo’, was reported to be moderately resistant to two species of SPW, Cylas puncticollis and Cylas brunneus. Resistance has been associated with the presence of hydroxycinnamic acids esters (HCAs), but the underlying genetic basis remains unknown. To determine the genetic basis of this resistance, a bi-parental sweetpotato population from a cross between the moderately resistant, white-fleshed ‘New Kawogo’ and the highly susceptible, orange-fleshed North American variety ‘Beauregard’ was evaluated for SPW resistance and genotyped with simple sequence repeat (SSR) markers to identify weevil resistance loci. SPW resistance was measured on the basis of field storage root SPW damage severity and total HCA ester concentrations. Moderate broad sense heritability (H2 = 0.49) was observed for weevil resistance in the population. Mean genotype SPW severity scores ranged from 1.0 to 9.0 and 25 progeny exhibited transgressive segregation for SPW resistance. Mean genotype total HCA ester concentrations were significantly different (P < 0.0001). A weak but significant correlation (r = 0.103, P = 0.015) was observed between total HCA ester concentration and SPW severity. A total of five and seven SSR markers were associated with field SPW severity and total HCA ester concentration, respectively. Markers IBS11, IbE5 and IbJ544b showed significant association with both field and HCA-based resistance, representing potential markers for the development of SPW resistant sweetpotato cultivars

Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques

A safe and effective vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be required to end the coronavirus disease 2019 (COVID-19) pandemic1–8. For global deployment and pandemic control, a vaccine that requires only a single immunization would be optimal. Here we show the immunogenicity and protective efficacy of a single dose of adenovirus serotype 26 (Ad26) vector-based vaccines expressing the SARS-CoV-2 spike (S) protein in non-human primates. Fifty-two rhesus macaques (Macaca mulatta) were immunized with Ad26 vectors that encoded S variants or sham control, and then challenged with SARS-CoV-2 by the intranasal and intratracheal routes9,10. The optimal Ad26 vaccine induced robust neutralizing antibody responses and provided complete or near-complete protection in bronchoalveolar lavage and nasal swabs after SARS-CoV-2 challenge. Titres of vaccine-elicited neutralizing antibodies correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate robust single-shot vaccine protection against SARS-CoV-2 in non-human primates. The optimal Ad26 vector-based vaccine for SARS-CoV-2, termed Ad26.COV2.S, is currently being evaluated in clinical trials

Games of Incomplete Information and Myopic Equilibria

A new concept of an equilibrium in games is introduced that solves an open question posed by A. Neyman

Optimization of Non-Coding Regions for a Non-Modified mRNA COVID-19 Vaccine

The CVnCoV (CureVac) mRNA vaccine for SARS-CoV-2 has recently been evaluated in a phase 2b/3 efficacy trial in humans1. CV2CoV is a second-generation mRNA vaccine with non-modified nucleosides but optimized non-coding regions and enhanced antigen expression. Here we report a head-to-head study of the immunogenicity and protective efficacy of CVnCoV and CV2CoV in nonhuman primates. We immunized 18 cynomolgus macaques with two doses of 12 ug of lipid nanoparticle formulated CVnCoV, CV2CoV, or sham (N=6/group). CV2CoV induced substantially higher binding and neutralizing antibodies, memory B cell responses, and T cell responses as compared with CVnCoV. CV2CoV also induced more potent neutralizing antibody responses against SARS-CoV-2 variants, including the delta variant. Moreover, CV2CoV proved comparably immunogenic to the BNT162b2 (Pfizer) vaccine in macaques. While CVnCoV provided partial protection against SARS-CoV-2 challenge, CV2CoV afforded more robust protection with markedly lower viral loads in the upper and lower respiratory tract. Binding and neutralizing antibody titers correlated with protective efficacy. These data demonstrate that optimization of non-coding regions can greatly improve the immunogenicity and protective efficacy of a non-modified mRNA SARS-CoV-2 vaccine in nonhuman primates