An elastic siderophore synthetase and rubbery substrates assemble multimeric linear and macrocyclic hydroxamic acid metal chelators.

The trihydroxamic acid bacterial siderophore desferrioxamine B (DFOB, 1) produced by the DesABCD biosynthetic cluster coordinates metals beyond Fe(iii), which identifies potential to modify this chelator type to broaden metal sequestration and/or delivery applications. Rather than producing discrete chelators by total chemical synthesis from native monomers including -hydroxy--succinyl-cadaverine (HSC, 2), the recombinant siderophore synthetase from CNB-440 (DesD) was used with different substrate combinations to produce biocombinatorial mixtures of hydroxamic acid chelators. The mixtures were screened with Ga(iii) or Zr(iv) as surrogates of immunological positron emission tomography (PET) imaging radiometals Ga(iii) or Zr(iv) to inform known or new coordination chemistry.

Elemental composition and potential toxicity of the riverine macrophyte Podostemum ceratophyllum Michx. reflects land use in eastern North America.

Land use influences surface water quality, often alleviating stoichiometric constraints on primary production and altering biogeochemical cycling. However, land use effects on nutrient content and potential trace metal accumulation in aquatic plants remain unclear, and high concentrations of metals and altered nutrient ratios could impact the health of herbivores and detritivores. We tested for land use effects on nutrient and trace metal accumulation in a widespread riverine macrophyte, Podostemum ceratophyllum, collected from 91 locations from Georgia to Maine, USA in 2014-2016.

A first-in-class dual-chelator theranostic agent designed for use with imaging-therapy radiometal pairs of different elements.

A covalent adduct of DFOB and DOTA separated by a l-lysine residue (DFOB-l-Lys- -DOTA) exhibited remarkable regioselective metal binding, with {H}-C NMR spectral shifts supporting Zr(iv) coordinating to the DFOB unit, and Lu(iii) coordinating to the DOTA unit. This first-in-class, dual-chelator theranostic design could enable the use of imaging-therapy radiometal pairs of different elements, such as Zr for positron emission tomography (PET) imaging and Lu for low-energy β-particle radiation therapy. DFOB-l-Lys- -DOTA was elaborated with an amine-terminated polyethylene glycol extender unit (PEG4) to give DFOB- -(PEG4)-l-Lys- -DOTA (compound D2) to enable installation of a phenyl-isothiocyanate group (Ph-NCS) for subsequent monoclonal antibody (mAb) conjugation (mAb = HuJ591).

Post COVID-19: a solution scan of options for preventing future zoonotic epidemics.

The crisis generated by the emergence and pandemic spread of COVID-19 has thrown into the global spotlight the dangers associated with novel diseases, as well as the key role of animals, especially wild animals, as potential sources of pathogens to humans. There is a widespread demand for a new relationship with wild and domestic animals, including suggested bans on hunting, wildlife trade, wet markets or consumption of wild animals. However, such policies risk ignoring essential elements of the problem as well as alienating and increasing hardship for local communities across the world, and might be unachievable at scale.

A Unified Framework for the Infection Dynamics of Zoonotic Spillover and Spread.

A considerable amount of disease is transmitted from animals to humans and many of these zoonoses are neglected tropical diseases. As outbreaks of SARS, avian influenza and Ebola have demonstrated, however, zoonotic diseases are serious threats to global public health and are not just problems confined to remote regions. There are two fundamental, and poorly studied, stages of zoonotic disease emergence: 'spillover', i.

Bat trait, genetic and pathogen data from large-scale investigations of African fruit bats, Eidolon helvum.

Bats, including African straw-coloured fruit bats (Eidolon helvum), have been highlighted as reservoirs of many recently emerged zoonotic viruses. This common, widespread and ecologically important species was the focus of longitudinal and continent-wide studies of the epidemiological and ecology of Lagos bat virus, henipaviruses and Achimota viruses. Here we present a spatial, morphological, demographic, genetic and serological dataset encompassing 2827 bats from nine countries over an 8-year period.

High turnover drives prolonged persistence of influenza in managed pig herds.

Pigs have long been hypothesized to play a central role in the emergence of novel human influenza A virus (IAV) strains, by serving as mixing vessels for mammalian and avian variants. However, the key issue of viral persistence in swine populations at different scales is ill understood. We address this gap using epidemiological models calibrated against seroprevalence data from Dutch finishing pigs to estimate the 'critical herd size' (CHS) for IAV persistence.

Eliminating bovine tuberculosis in cattle and badgers: insight from a dynamic model.

Bovine tuberculosis (BTB) is a multi-species infection that commonly affects cattle and badgers in Great Britain. Despite years of study, the impact of badgers on BTB incidence in cattle is poorly understood. Using a two-host transmission model of BTB in cattle and badgers, we find that published data and parameter estimates are most consistent with a system at the threshold of control.

Seven challenges in modeling pathogen dynamics within-host and across scales.

The population dynamics of infectious disease is a mature field in terms of theory and to some extent, application. However for microparasites, the theory and application of models of the dynamics within a single infected host is still an open field. Further, connecting across the scales--from cellular to host level, to population level--has potential to vastly improve our understanding of pathogen dynamics and evolution.

Nine challenges in modelling the emergence of novel pathogens.

Studying the emergence of novel infectious agents involves many processes spanning host species, spatial scales, and scientific disciplines. Mathematical models play an essential role in combining insights from these investigations and drawing robust inferences from field and experimental data. We describe nine challenges in modelling the emergence of novel pathogens, emphasizing the interface between models and data.

Potential benefits of cattle vaccination as a supplementary control for bovine tuberculosis.

Vaccination for the control of bovine tuberculosis (bTB) in cattle is not currently used within any international control program, and is illegal within the EU. Candidate vaccines, based upon Mycobacterium bovis bacillus Calmette-Guérin (BCG) all interfere with the action of the tuberculin skin test, which is used to determine if animals, herds and countries are officially bTB-free. New diagnostic tests that Differentiate Infected from Vaccinated Animals (DIVA) offer the potential to introduce vaccination within existing eradication programs.

The demography of free-roaming dog populations and applications to disease and population control.

Understanding the demography of domestic dog populations is essential for effective disease control, particularly of canine-mediated rabies. Demographic data are also needed to plan effective population management. However, no study has comprehensively evaluated the contribution of demographic processes (i.

Using modelling to disentangle the relative contributions of zoonotic and anthroponotic transmission: the case of lassa fever.

Background: Zoonotic infections, which transmit from animals to humans, form the majority of new human pathogens. Following zoonotic transmission, the pathogen may already have, or may acquire, the ability to transmit from human to human. With infections such as Lassa fever (LF), an often fatal, rodent-borne, hemorrhagic fever common in areas of West Africa, rodent-to-rodent, rodent-to-human, human-to-human and even human-to-rodent transmission patterns are possible.

Achieving population-level immunity to rabies in free-roaming dogs in Africa and Asia.

Canine rabies can be effectively controlled by vaccination with readily available, high-quality vaccines. These vaccines should provide protection from challenge in healthy dogs, for the claimed period, for duration of immunity, which is often two or three years. It has been suggested that, in free-roaming dog populations where rabies is endemic, vaccine-induced protection may be compromised by immuno-suppression through malnutrition, infection and other stressors.

Characteristics and Risk Perceptions of Ghanaians Potentially Exposed to Bat-Borne Zoonoses through Bushmeat.

Emerging zoonotic pathogens from wildlife pose increasing public health threats globally. Bats, in particular, host an array of zoonotic pathogens, yet there is little research on how bats and humans interact, how people perceive bats and their accompanying disease risk, or who is most at risk. Eidolon helvum, the largest and most abundant African fruit bat species, is widely hunted and eaten in Ghana and also carries potentially zoonotic pathogens.

Bat flight and zoonotic viruses.

Bats are sources of high viral diversity and high-profile zoonotic viruses worldwide. Although apparently not pathogenic in their reservoir hosts, some viruses from bats severely affect other mammals, including humans. Examples include severe acute respiratory syndrome coronaviruses, Ebola and Marburg viruses, and Nipah and Hendra viruses.

Age-dependent patterns of bovine tuberculosis in cattle.

Bovine tuberculosis (BTB) is an important livestock disease, seriously impacting cattle industries in both industrialised and pre-industrialised countries. Like TB in other mammals, infection is life long and, if undiagnosed, may progress to disease years after exposure. The risk of disease in humans is highly age-dependent, however in cattle, age-dependent risks have yet to be quantified, largely due to insufficient data and limited diagnostics.