Absence of MERS-CoV antibodies in feral camels in Australia: Implications for the pathogen's origin and spread

Middle East respiratory syndrome coronavirus (MERS-CoV) infections continue to be a serious emerging disease problem internationally with well over 1000 cases and a major outbreak outside of the Middle East region. While the hypothesis that dromedary camels are the likely major source of MERS-CoV infection in humans is gaining acceptance, conjecture continues over the original natural reservoir host(s) and specifically the role of bats in the emergence of the virus. Dromedary camels were imported to Australia, principally between 1880 and 1907 and have since become a large feral population inhabiting extensive parts of the continent. Here we report that during a focussed surveillance study, no serological evidence was found for the presence of MERS-CoV in the camels in the Australian population. This finding presents various hypotheses about the timing of the emergence and spread of MERS-CoV throughout populations of camels in Africa and Asia, which can be partially resolved by testing sera from camels from the original source region, which we have inferred was mainly northwestern Pakistan. In addition, we identify bat species which overlap (or neighbour) the range of the Australian camel population with a higher likelihood of carrying CoVs of the same lineage as MERS-CoV. Both of these proposed follow-on studies are examples of "proactive surveillance", a concept that has particular relevance to a One Health approach to emerging zoonotic diseases with a complex epidemiology and aetiology

A transdisciplinary and community-driven database to unravel subduction zone initiation

Subduction zones are pivotal for the recycling of Earth’s outer layer into its interior. However, the conditions under which new subduction zones initiate are enigmatic. Here, we constructed a transdisciplinary database featuring detailed analysis of more than a dozen documented subduction zone initiation events from the last hundred million years. Our initial findings reveal that horizontally forced subduction zone initiation is dominant over the last 100 Ma, and that most initiation events are proximal to pre-existing subduction zones. The SZI Database is expandable to facilitate access to the most current understanding of subduction zone initiation as research progresses, providing a community platform that establishes a common language to sharpen discussion across the Earth Science community

Through the labyrinth of yesteryears

Background Allergy to dog (Canis familiaris) is a worldwide common cause of asthma and allergic rhinitis. However, dander extract in routine diagnostics is not an optimal predictor of IgE-mediated dog allergy. Our objective was to evaluate saliva as an allergen source for improved diagnostics of allergy to dog. Methods IgE-binding proteins in dog saliva and dander extract were analysed by immunoblot and mass spectrometry (LC-MS/MS) using pooled or individual sera from dog-allergic patients (n=13). Sera from 59 patients IgE positive to dander and 55 patients IgE negative to dander but with symptoms to dog were analysed for IgE against saliva and dander by ELISA. Basophil stimulation with dog saliva and dander extract was measured by flow cytometry among three dog-allergic patients. Additionally, IgE-binding protein profiles of saliva from different breeds were investigated by immunoblot. Results Greater number and diversity of IgE-binding proteins was found in saliva compared to dander extract and varied among dog breeds. In saliva, Can f 1, 2, 3 and 6 were identified but also four new saliva allergen candidates. The majority of the 59 dog danderpositive sera (n=44) were IgE positive to dog saliva. Among patients IgE negative to dander, but with symptoms to dog, 20% were IgE positive to saliva. The biological activity of saliva was confirmed by basophil degranulation. Conclusions Dog saliva is an allergen source for improved diagnostics of dog allergy. The IgE-binding protein profile of saliva from different dogs varies.Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/3488

GATA3-driven Th2 responses inhibit TGF-beta1-induced FOXP3 expression and the formation of regulatory T cells.

Transcription factors act in concert to induce lineage commitment towards Th1, Th2, or T regulatory (Treg) cells, and their counter-regulatory mechanisms were shown to be critical for polarization between Th1 and Th2 phenotypes. FOXP3 is an essential transcription factor for natural, thymus-derived (nTreg) and inducible Treg (iTreg) commitment; however, the mechanisms regulating its expression are as yet unknown. We describe a mechanism controlling iTreg polarization, which is overruled by the Th2 differentiation pathway. We demonstrated that interleukin 4 (IL-4) present at the time of T cell priming inhibits FOXP3. This inhibitory mechanism was also confirmed in Th2 cells and in T cells of transgenic mice overexpressing GATA-3 in T cells, which are shown to be deficient in transforming growth factor (TGF)-beta-mediated FOXP3 induction. This inhibition is mediated by direct binding of GATA3 to the FOXP3 promoter, which represses its transactivation process. Therefore, this study provides a new understanding of tolerance development, controlled by a type 2 immune response. IL-4 treatment in mice reduces iTreg cell frequency, highlighting that therapeutic approaches that target IL-4 or GATA3 might provide new preventive strategies facilitating tolerance induction particularly in Th2-mediated diseases, such as allergy

In Vitro Evolution of Allergy Vaccine Candidates, with Maintained Structure, but Reduced B Cell and T Cell Activation Capacity

Allergy and asthma to cat (Felis domesticus) affects about 10% of the population in affluent countries. Immediate allergic symptoms are primarily mediated via IgE antibodies binding to B cell epitopes, whereas late phase inflammatory reactions are mediated via activated T cell recognition of allergen-specific T cell epitopes. Allergen-specific immunotherapy relieves symptoms and is the only treatment inducing a long-lasting protection by induction of protective immune responses. The aim of this study was to produce an allergy vaccine designed with the combined features of attenuated T cell activation, reduced anaphylactic properties, retained molecular integrity and induction of efficient IgE blocking IgG antibodies for safer and efficacious treatment of patients with allergy and asthma to cat. The template gene coding for rFel d 1 was used to introduce random mutations, which was subsequently expressed in large phage libraries. Despite accumulated mutations by up to 7 rounds of iterative error-prone PCR and biopanning, surface topology and structure was essentially maintained using IgE-antibodies from cat allergic patients for phage enrichment. Four candidates were isolated, displaying similar or lower IgE binding, reduced anaphylactic activity as measured by their capacity to induce basophil degranulation and, importantly, a significantly lower T cell reactivity in lymphoproliferative assays compared to the original rFel d 1. In addition, all mutants showed ability to induce blocking antibodies in immunized mice.The approach presented here provides a straightforward procedure to generate a novel type of allergy vaccines for safer and efficacious treatment of allergic patients

Shotgun Phage Display - Selection for Bacterial Receptins or other Exported Proteins

Shotgun phage display cloning involves construction of libraries from randomly fragmented bacterial chromosomal DNA, cloned genes, or eukaryotic cDNAs, into a phagemid vector. The library obtained consists of phages expressing polypeptides corresponding to all genes encoded by the organism, or overlapping peptides derived from the cloned gene. From such a library, polypeptides with affinity for another molecule can be isolated by affinity selection, panning. The technique can be used to identify bacterial receptins and identification of their minimal binding domain, and but also to identify epitopes recognised by antibodies. In addition, after modification of the phagemid vector, the technique has also been used to identify bacterial extracytoplasmic proteins

Aspergillus Genomes and the Aspergillus Cloud

Aspergillus Genomes is a public resource for viewing annotated genes predicted by various Aspergillus sequencing projects. It has arisen from the union of two significant resources: the Aspergillus/Aspergillosis website and the Central Aspergillus Data REpository (CADRE). The former has primarily served the medical community, providing information about Aspergillus and associated diseases to medics, patients and scientists; the latter has focused on the fungal genomic community, providing a central repository for sequences and annotation extracted from Aspergillus Genomes. By merging these databases, genomes benefit from extensive cross-linking with medical information to create a unique resource, spanning genomics and clinical aspects of the genus. Aspergillus Genomes is accessible from http://www.aspergillus-genomes.org.uk

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

Why does cultural policy change? Policy discourse and policy subsystem : a case study of the evolution of cultural policy in Catalonia

This is an Author's Accepted Manuscript of an article published in International journal of cultural policy, Vol. 18, N. 1 (2012), p. 13-30 [copyright Taylor & Francis]Culture has come to play a fundamental strategic role in the territorial development that seeks to integrate knowledge economy with social cohesion, governance and sustainability. However, cultural policies have been unable to respond to the dilemmas and expectations that this new order presents. In order to appreciate the consequences of this process, it is essential to gain a better understanding of cultural policy change dynamics. This paper develops a framework for analysing cultural policy stability and change and applies it to the evolution of cultural policy in Catalonia. Both policy continuity and change are conditioned by the evolution of policy discourse on culture and the characteristics of the cultural policy subsystem. Within this framework, we also take into account the role of factors that are exogenous to the cultural domain. Lastly this paper addresses particular characteristics of cultural policy change in regions or stateless nations

Seladin-1 expression is regulated by promoter methylation in adrenal cancer

<p>Abstract</p> <p>Background</p> <p>Seladin-1 overexpression exerts a protective mechanism against apoptosis. Seladin-1 mRNA is variably expressed in normal human tissues. Adrenal glands show the highest levels of seladin-1 expression, which are significantly reduced in adrenal carcinomas (ACC). Since up to now seladin-1 mutations were not described, we investigated whether promoter methylation could account for the down-regulation of seladin-1 expression in ACC.</p> <p>Methods</p> <p>A methylation sensitive site was identified in the seladin-1 gene. We treated DNA extracted from two ACC cell lines (H295R and SW13) with the demethylating agent 5-Aza-2-deoxycytidine (5-Aza). Furthermore, to evaluate the presence of an epigenetic regulation also 'in vivo', seladin-1 methylation and its mRNA expression were measured in 9 ACC and in 5 normal adrenal glands.</p> <p>Results</p> <p>The treatment of cell lines with 5-Aza induced a significant increase of seladin-1 mRNA expression in H295R (fold increase, F.I. = 1.8; p = 0.02) and SW13 (F.I. = 2.9; p = 0.03). In ACC, methylation density of seladin-1 promoter was higher (2682 ± 686) than in normal adrenal glands (362 ± 97; p = 0.02). Seladin-1 mRNA expression in ACC (1452 ± 196) was significantly lower than in normal adrenal glands (3614 ± 949; p = 0.01).</p> <p>Conclusion</p> <p>On this basis, methylation could be involved in the altered pattern of seladin-1 gene expression in ACC.</p