Identification of Novel Cetacean Poxviruses in Cetaceans Stranded in South West England

Poxvirus infections in marine mammals have been mainly reported through their clinical lesions and electron microscopy (EM). Poxvirus particles in association with such lesions have been demonstrated by EM and were previously classified as two new viruses, cetacean poxvirus 1 (CePV-1) and cetacean poxvirus 2 (CePV-2). In this study, epidermal pox lesions in cetaceans stranded in South West England (Cornwall) between 2008 and 2012 were investigated by electron microscopy and molecular analysis. PCR and sequencing of a highly conserved region within the viral DNA polymerase gene ruled out both parapoxand orthopoxviruses. Moreover, phylogenetic analysis of the PCR product clustered the sequences with those previously described as cetacean poxviruses. However, taking the close genetic distance of this gene fragment across the family of poxviridae into account, it is reasonable to postulate further, novel cetacean poxvirus species. The nucleotide similarity within each cluster (tentative species) detected ranged from 98.6% to 100%, whilst the similarity between the clusters was no more than 95%. The detection of several species of poxvirus in different cetacean species confirms the likelihood of a heterogeneous cetacean poxvirus genus, comparable to the heterogeneity observed in other poxvirus genera

Future evolution and uncertainty of river flow regime change in a deglaciating river basin

The flow regimes of glacier-fed rivers are sensitive to climate change due to strong climate–cryosphere–hydrosphere interactions. Previous modelling studies have projected changes in annual and seasonal flow magnitude but neglect other changes in river flow regime that also have socio-economic and environmental impacts. This study employs a signature-based analysis of climate change impacts on the river flow regime for the deglaciating Virkisá river basin in southern Iceland. Twenty-five metrics (signatures) are derived from 21st century projections of river flow time series to evaluate changes in different characteristics (magnitude, timing and variability) of river flow regime over sub-daily to decadal timescales. The projections are produced by a model chain that links numerical models of climate and glacio-hydrology. Five components of the model chain are perturbed to represent their uncertainty including the emission scenario, numerical climate model, downscaling procedure, snow/ice melt model and runoff-routing model. The results show that the magnitude, timing and variability of glacier-fed river flows over a range of timescales will change in response to climate change. For most signatures there is high confidence in the direction of change, but the magnitude is uncertain. A decomposition of the projection uncertainties using analysis of variance (ANOVA) shows that all five perturbed model chain components contribute to projection uncertainty, but their relative contributions vary across the signatures of river flow. For example, the numerical climate model is the dominant source of uncertainty for projections of high-magnitude, quick-release flows, while the runoff-routing model is most important for signatures related to low-magnitude, slow-release flows. The emission scenario dominates mean monthly flow projection uncertainty, but during the transition from the cold to melt season (April and May) the snow/ice melt model contributes up to 23&thinsp;% of projection uncertainty. Signature-based decompositions of projection uncertainty can be used to better design impact studies to provide more robust projections.</p

Taxing the Informal Economy: The Current State of Knowledge and Agendas for Future Research

This paper reviews the literature on taxation of the informal economy, taking stock of key debates and drawing attention to recent innovations. Conventionally, the debate on whether to tax has frequently focused on the limited revenue potential, high cost of collection, and potentially adverse impact on small firms. Recent arguments have increasingly emphasised the more indirect benefits of informal taxation in relation to economic growth, broader tax compliance, and governance. More research is needed, we argue, into the relevant costs and benefits for all, including quasi-voluntary compliance, political and administrative incentives for reform, and citizen-state bargaining over taxation

Nonequilibrium effective field theory for absorbing state phase transitions in driven open quantum spin systems

Phase transitions to absorbing states are among the simplest examples of critical phenomena out of equilibrium. The characteristic feature of these models is the presence of a fluctuationless configuration which the dynamics cannot leave, which has proved a rather stringent requirement in experiments. Recently, a proposal to seek such transitions in highly tuneable systems of cold atomic gases offers to probe this physics and, at the same time, to investigate the robustness of these transitions to quantum coherent effects. Here we specifically focus on the interplay between classical and quantum fluctuations in a simple driven open quantum model which, in the classical limit, reproduces a contact process, which is known to undergo a continuous transition in the "directed percolation" universality class. We derive an effective long-wavelength field theory for the present class of open spin systems and show that, due to quantum fluctuations, the nature of the transition changes from second to first order, passing through a bicritical point which appears to belong instead to the "tricritical directed percolation" class

Comparative micro-epidemiology of pathogenic avian influenza virus outbreaks in a wild bird population

Understanding the epidemiological dynamics of highly pathogenic avian influenza virus (HPAIV) in wild birds is crucial for guiding effective surveillance and control measures. The spread of H5 HPAIV has been well characterized over large geographical and temporal scales. However, information about the detailed dynamics and demographics of individual outbreaks in wild birds is rare and important epidemiological parameters remain unknown. We present data from a wild population of long-lived birds (mute swans; Cygnus olor) that has experienced three outbreaks of related H5 HPAIVs in the past decade, specifically, H5N1 (2007), H5N8 (2016) and H5N6 (2017). Detailed demographic data were available and intense sampling was conducted before and after the outbreaks; hence the population is unusually suitable for exploring the natural epidemiology, evolution and ecology of HPAIV in wild birds. We show that key epidemiological features remain remarkably consistent across multiple outbreaks, including the timing of virus incursion and outbreak duration, and the presence of a strong age-structure in morbidity that likely arises from an equivalent age-structure in immunological responses. The predictability of these features across a series of outbreaks in a complex natural population is striking and contributes to our understanding of HPAIV in wild birds

Identification of a Novel Synaptic Protein, TMTC3, Involved in Periventricular Nodular Heterotopia with Intellectual Disability and Epilepsy

Defects in neuronal migration cause brain malformations, which are associated with intellectual disability (ID) and epilepsy. Using exome sequencing, we identified compound heterozygous variants (p.Arg71His and p. Leu729ThrfsTer6) in TMTC3, encoding transmembrane and tetratricopeptide repeat containing 3, in four siblings with nocturnal seizures and ID. Three of the four siblings have periventricular nodular heterotopia (PVNH), a common brain malformation caused by failure of neurons to migrate from the ventricular zone to the cortex. Expression analysis using patient-derived cells confirmed reduced TMTC3 transcript levels and loss of the TMTC3 protein compared to parental and control cells. As TMTC3 function is currently unexplored in the brain, we gathered support for a neurobiological role for TMTC3 by generating flies with post-mitotic neuron-specific knockdown of the highly conserved Drosophila melanogaster TMTC3 ortholog, CG4050/tmtc3. Neuron-specific knockdown of tmtc3 in flies resulted in increased susceptibility to induced seizures. Importantly, this phenotype was rescued by neuron-specific expression of human TMTC3, suggesting a role for TMTC3 in seizure biology. In addition, we observed co-localization of TMTC3 in the rat brain with vesicular GABA transporter (VGAT), a presynaptic marker for inhibitory synapses. TMTC3 is localized at VGAT positive pre-synaptic terminals and boutons in the rat hypothalamus and piriform cortex, suggesting a role for TMTC3 in the regulation of GABAergic inhibitory synapses. TMTC3 did not co-localize with Vglut2, a presynaptic marker for excitatory neurons. Our data identified TMTC3 as a synaptic protein that is involved in PVNH with ID and epilepsy, in addition to its previously described association with cobblestone lissencephaly

Detection and Localisation of PrPSc in the Liver of Sheep Infected with Scrapie and Bovine Spongiform Encephalopathy

Prions are largely contained within the nervous and lymphoid tissue of transmissible spongiform encephalopathy (TSE) infected animals. However, following advances in diagnostic sensitivity, PrPSc, a marker for prion disease, can now be located in a wide range of viscera and body fluids including muscle, saliva, blood, urine and milk, raising concerns that exposure to these materials could contribute to the spread of disease in humans and animals. Previously we demonstrated low levels of infectivity in the liver of sheep experimentally challenged with bovine spongiform encephalopathy. In this study we show that PrPSc accumulated in the liver of 89% of sheep naturally infected with scrapie and 100% of sheep challenged with BSE, at both clinical and preclinical stages of the disease. PrPSc was demonstrated in the absence of obvious inflammatory foci and was restricted to isolated resident cells, most likely Kupffer cells

Integrative omics identifies conserved and pathogen-specific responses of sepsis-causing bacteria

Even in the setting of optimal resuscitation in high-income countries severe sepsis and septic shock have a mortality of 20–40%, with antibiotic resistance dramatically increasing this mortality risk. To develop a reference dataset enabling the identification of common bacterial targets for therapeutic intervention, we applied a standardized genomic, transcriptomic, proteomic and metabolomic technological framework to multiple clinical isolates of four sepsis-causing pathogens: Escherichia coli, Klebsiella pneumoniae species complex, Staphylococcus aureus and Streptococcus pyogenes. Exposure to human serum generated a sepsis molecular signature containing global increases in fatty acid and lipid biosynthesis and metabolism, consistent with cell envelope remodelling and nutrient adaptation for osmoprotection. In addition, acquisition of cholesterol was identified across the bacterial species. This detailed reference dataset has been established as an open resource to support discovery and translational research