Susceptibility of sheep to experimental co-infection with the ancestral lineage of SARS-CoV-2 and its alpha variant

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for a global pandemic that has had significant impacts on human health and economies worldwide. SARS-CoV-2 is highly transmissible and the cause of coronavirus disease 2019 (COVID-19) in humans. A wide range of animal species have also been shown to be susceptible to SARS-CoV-2 infection by experimental and/or natural infections. Domestic and large cats, mink, ferrets, hamsters, deer mice, white-tailed deer, and non-human primates have been shown to be highly susceptible, whereas other species such as mice, dogs, pigs, and cattle appear to be refractory to infection or have very limited susceptibility. Sheep (Ovis aries) are a commonly farmed domestic ruminant that have not previously been thoroughly investigated for their susceptibility to SARS-CoV-2. Therefore, we performed in vitro and in vivo studies which consisted of infection of ruminant-derived cell cultures and experimental challenge of sheep to investigate their susceptibility to SARS-CoV-2. Our results showed that sheep-derived cell cultures support SARS-CoV-2 replication. Furthermore, experimental challenge of sheep demonstrated limited infection with viral RNA shed in nasal and oral swabs primarily at 1-day post challenge (DPC), and also detected in the respiratory tract and lymphoid tissues at 4 and 8 DPC. Sero-reactivity was also observed in some of the principal infected sheep but not the contact sentinels, indicating that transmission to co-mingled naive sheep was not highly efficient; hovewer, viral RNA was detected in some of the respiratory tract tissues of sentinel animals at 21 DPC. Furthermore, we used challenge inoculum consisting of a mixture of two SARS-CoV-2 isolates, representatives of the ancestral lineage A and the B.1.1.7-like alpha variant of concern (VOC), to study competition of the two virus strains. Our results indicate that sheep show low susceptibility to SARS-CoV-2 infection, and that the alpha VOC outcompeted the ancestral lineage A strain.

Influenza Neuraminidase Characteristics and Potential as a Vaccine Target

Neuraminidase of influenza A and B viruses plays a critical role in the virus life cycle and is an important target of the host immune system. Here, we highlight the current understanding of influenza neuraminidase structure, function, antigenicity, immunogenicity, and immune protective potential. Neuraminidase inhibiting antibodies have been recognized as correlates of protection against disease caused by natural or experimental influenza A virus infection in humans. In the past years, we have witnessed an increasing interest in the use of influenza neuraminidase to improve the protective potential of currently used influenza vaccines. A number of well-characterized influenza neuraminidase-specific monoclonal antibodies have been described recently, most of which can protect in experimental challenge models by inhibiting the neuraminidase activity or by Fc receptor-dependent mechanisms. The relative instability of the neuraminidase poses a challenge for protein-based antigen design. We critically review the different solutions that have been proposed to solve this problem, ranging from the inclusion of stabilizing heterologous tetramerizing zippers to the introduction of inter-protomer stabilizing mutations. Computationally engineered neuraminidase antigens have been generated that offer broad, within subtype protection in animal challenge models. We also provide an overview of modern vaccine technology platforms that are compatible with the induction of robust neuraminidase-specific immune responses. In the near future, we will likely see the implementation of influenza vaccines that confront the influenza virus with a double punch: targeting both the hemagglutinin and the neuraminidase.

Ultrafast base rotations mediate a solvent-assisted back-electron transfer in UV-excited DNA single strands

The photochemistry of DNA systems is characterized by the ultraviolet (UV) absorption of π-stacked nucleobases, resulting in exciton states delocalized over several bases. As their relaxation sensitively depends on local stacking conformations, disentangling the ensuing electronic and structural dynamics has remained an experimental challenge, despite their fundamental role in protecting the genome from potentially harmful UV radiation. Here we use transient absorption and transient absorption anisotropy spectroscopy with broadband femtosecond deep-UV pulses (250-360 nm) to resolve the exciton dynamics of UV-excited adenosine single strands under physiological conditions. Due to the exceptional deep-UV bandwidth and polarization sensitivity of our experimental approach, we simultaneously resolve the population dynamics, charge-transfer (CT) character and conformational changes encoded in the UV transition dipoles of the π-stacked nucleotides. Whilst UV excitation forms fully charge-separated CT excitons in less than 0.3 ps, we find that most decay back to the ground state via a solvent-assisted back-electron transfer. This deactivation mechanism is accompanied by a structural relaxation of the photoexcited base-stack, which we identify as an inter-base rotation of the nucleotides. Our results finally complete the exciton relaxation mechanism for adenosine single strands and offer a direct view into the coupling of electronic and structural dynamics in aggregated photochemical systems.

Why intracranial electrical stimulation of the human brain suggests an essential role for prefrontal cortex in conscious processing: a commentary on Raccah et al.

We read with interest the synthesis by Raccah and colleagues on the perturbations of consciousexperience elicited by intracranial electrical stimulation (iES) of the prefrontal cortex (PFC) in awakeneurosurgical patients. The main outcome of the review is the report that iES of the PFC shows fewercausal changes of conscious experience than iES of posterior sensory areas. The authors interpretedthis finding as a challenge to neuroscientific theories of conscious processing that attribute a centralrole to PFC, such a Global Neuronal Workspace Theory (GNWT) and Higher Order Thought theory(HOT). We agree that this anterior vs posterior issue may offer an experimental challenge that thepresent theories of conscious processing have to take up, and we provide here a list of seven majorpoints that begin to specify a GNWT account for the observations compiled by Raccah and colleaguestogether with more recent, unmentioned, data.

Design of a system for controlling a levitating sphere in superfluid 3He at extremely low temperatures

We present a new mechanical probe to study the properties of superfluid 3He at microkelvin temperatures down to 100 μK. The setup consists of a set of coils for levitating a superconducting sphere and controlling its motion in a wide variety of regimes. In particular, the realisation of motion of a levitating body at a uniform velocity presents both an experimental challenge and a promising direction into the study of the edge states in topological superfluid 3He-B. We include the theoretical study of the device stability and simulations to illustrate the capabilities of the control system.

Influence of sex, season and environmental air quality on experimental human pneumococcal carriage acquisition

Streptococcus pneumoniae (pneumococcus) is the most common identified bacterial cause of pneumonia, and the leading infectious cause of death in children under five years of age worldwide. Pneumococcal disease follows a seasonal pattern with increased incidence during winter. Pneumonia burden is also associated with poor air quality. Nasopharyngeal carriage of the bacterium is a pre-requisite of invasive disease.We aimed to determine if susceptibility to nasopharyngeal pneumococcal carriage varied by season, and which environmental factors might explain such variation. We also evaluated the influence of sex on susceptibility of carriage. We collated data from five studies in which human volunteers underwent intranasal pneumococcal challenge. Generalised linear mixed effects models were used to identify factors associated with altered risk of carriage acquisition, specifically climate and air-quality data.During 2011-2017, 374 healthy adults were challenged with type 6B pneumococcus. Odds of carriage were significantly lower in males (OR, 0.61; 95% CI, 0.40-0.92; p = 0.02), and higher with cooler temperatures (OR, 0.79; 95% CI, 0.63-0.99; p = 0.04). Likelihood of carriage also associated with lower concentrations of local fine particulate matter concentrations (PM2.5) and increased local rainfall.In contrast to epidemiologic series, experimental challenge allowed us to test propensity to acquisition during controlled exposures; immunologic explanations for sex and climatic differences should be sought.

The $$\uptau $$ challenges at FCC-ee

At FCC-ee, about $$1.7 \times 10^{11}\,\hbox {Z} \rightarrow \uptau ^+\uptau ^-$$ 1.7 × 10 11 Z → τ + τ - events will be produced. This high statistics in the clean $$\hbox {e}^+\hbox {e}^-$$ e + e - environment opens the possibility of much improved determinations of $$\uptau $$ τ -lepton properties and, via the measurement of the $$\uptau $$ τ polarisation, of the neutral-current couplings of electrons and $$\tau $$ τ s. Improved measurements of $$\uptau $$ τ -lepton properties—lifetime, leptonic branching fractions, and mass—allow important tests of lepton universality. The experimental challenge is to match as far as possible statistical uncertainties generally at the $$10^{-5}$$ 10 - 5 level. This applies in particular to the lifetime measurement, which is derived from the 2.2-mm $$\uptau $$ τ average flight distance, and for the branching fraction and polarisation measurements, where the cross-channel contamination is of particular concern. These issues raise strict detector requirements, in particular, on the accuracy of the construction and alignment of the vertex detector and of the precise calorimetric separation and measurement of photons and $$\uppi ^0$$ π 0 s in the collimated $$\uptau $$ τ decay topologies.