Although most mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome are expected to be either deleterious and swiftly purged or relatively neutral, a small proportion will affect functional properties and may alter infectivity, disease severity or interactions with host immunity. The emergence of SARS-CoV-2 in late 2019 was followed by a period of relative evolutionary stasis lasting about 11 months. Since late 2020, however, SARS-CoV-2 evolution has been characterized by the emergence of sets of mutations, in the context of ‘variants of concern’, that impact virus characteristics, including transmissibility and antigenicity, probably in response to the changing immune profile of the human population. There is emerging evidence of reduced neutralization of some SARS-CoV-2 variants by postvaccination serum; however, a greater understanding of correlates of protection is required to evaluate how this may impact vaccine effectiveness. Nonetheless, manufacturers are preparing platforms for a possible update of vaccine sequences, and it is crucial that surveillance of genetic and antigenic changes in the global virus population is done alongside experiments to elucidate the phenotypic impacts of mutations. In this Review, we summarize the literature on mutations of the SARS-CoV-2 spike protein, the primary antigen, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets.

The human respiratory tract hosts a diverse community of cocirculating viruses that are responsible for acute respiratory infections. This shared niche provides the opportunity for virus-virus interactions which have the potential to affect individual infection risks and in turn influence dynamics of infection at population scales. However, quantitative evidence for interactions has lacked suitable data and appropriate analytical tools. Here, we expose and quantify interactions among respiratory viruses using bespoke analyses of infection time series at the population scale and coinfections at the individual host scale. We analyzed diagnostic data from 44,230 cases of respiratory illness that were tested for 11 taxonomically broad groups of respiratory viruses over 9 y. Key to our analyses was accounting for alternative drivers of correlated infection frequency, such as age and seasonal dependencies in infection risk, allowing us to obtain strong support for the existence of negative interactions between influenza and noninfluenza viruses and positive interactions among noninfluenza viruses. In mathematical simulations that mimic 2-pathogen dynamics, we show that transient immune-mediated interference can cause a relatively ubiquitous common cold-like virus to diminish during peak activity of a seasonal virus, supporting the potential role of innate immunity in driving the asynchronous circulation of influenza A and rhinovirus. These findings have important implications for understanding the linked epidemiological dynamics of viral respiratory infections, an important step towards improved accuracy of disease forecasting models and evaluation of disease control interventions. epidemiology | virology | ecology

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This study examines four months of online discourse of 22 Grade 4 students engaged in efforts to advance their understanding of optics. Their work is part of a school-wide knowledge building initiative, the essence of which is giving students collective responsibility for idea improvement. This goal is supported by software-Knowledge Forum-designed to provide a public and collaborative space for continual improvement of ideas. A new analytic tool-inquiry threads-was developed to analyze the discourse used by these students as they worked in this environment. Data analyses focus on four knowledge building principles: idea improvement; real ideas, authentic problems (involving concrete/empirical and abstract/conceptual artifacts); community knowledge (knowledge constructed for the benefit of the community as a whole); and constructive use of authoritative sources. Results indicate that these young students generated theories and explanation-seeking questions, designed experiments to produce real-world empirical data to support their theories, located and introduced expert resources, revised ideas, and responded to problems and ideas that emerged as community knowledge

Preface 54There is much interest in using Earth Observation (EO) technology to track biodiversity, 55 ecosystem functions, and ecosystem services, understandable given the fast pace of 56 biodiversity loss. However, because most biodiversity is invisible to EO, EO-based 57 indicators could be misleading, which can reduce the effectiveness of nature 58 conservation and even unintentionally decrease conservation effort. We describe an 59 approach that combines automated recording devices, high-throughput DNA Meeting the Aichi Biodiversity Targets 64From Google Earth to airborne sensors, the Copernicus Sentinels, and cube satellites, 65Earth Observation is undergoing a rapid expansion in capacity, accessibility, resolution, 66and signal-to-noise ratio, resulting in a recognised shift in our capability for using 67 remote-sensing technologies to monitor biophysical processes on land and water [1][2][3] . 68These advances are motivating calls to use Earth Observation products to manage our 69 natural environment and to track progress toward global and national policy targets on 70 biodiversity and ecosystem services [4][5][6] . Foremost among these policies are the Strategic 71Plan for Biodiversity and the Aichi Biodiversity Targets, which were adopted in 2010 by products (net primary productivity and fire incidence) that could serve as Essential 108Biodiversity Variables for the Sahara, despite this biome's suitability for remote sensing 109 due to its visible biodiversity hotspots, remoteness, and availability of long time series. 110Many of the Aichi Targets require data with species-level resolution, either because some 111 species are direct policy targets (e.g. Target 9: "invasive species controlled or eradicated") 112 or because species compositional data define the metric (e.g. Target 11: "protected areas 113 are ecologically representative and conserved effectively"). species, but information could be 'borrowed' from data-rich species to increase the 294 precision of predictions for rare species. These procedures were able to compensate for 295 the fact that only 134 total bird species had been detected in the survey, which is less The GDM was parameterised with a training dataset of 2280 surveys and fourteen 303 environmental variables and explained 57% of the variation in beta diversity. In addition, for linking pure-EO data to biodiversity. 382The major remaining components of uncertainty relate to generalisability, because only a 383 single FSC-certified reserve was sampled; the applicability of results to arboreal species, 384 which tend to be detected more frequently in forests with disturbed canopy but are not 385 necessarily more widespread in these forests; and wide confidence intervals around 386 parameter estimates for some species as a consequence of sparse data and a fairly 394Another example of the CEOBE approach is the use of Generalised Dissimilarity 395Modelling to connect EO-derived metrics of habitat degradation and fragmentation 89,90 396 to over 300 million records of more ...

Determining phenotype from genetic data is a fundamental challenge. Identification of emerging antigenic variants among circulating influenza viruses is critical to the vaccine virus selection process, with vaccine effectiveness maximized when constituents are antigenically similar to circulating viruses. Hemagglutination inhibition (HI) assay data are commonly used to assess influenza antigenicity. Here, sequence and 3-D structural information of hemagglutinin (HA) glycoproteins were analyzed together with corresponding HI assay data for former seasonal influenza A(H1N1) virus isolates (1997–2009) and reference viruses. The models developed identify and quantify the impact of eighteen amino acid substitutions on the antigenicity of HA, two of which were responsible for major transitions in antigenic phenotype. We used reverse genetics to demonstrate the causal effect on antigenicity for a subset of these substitutions. Information on the impact of substitutions allowed us to predict antigenic phenotypes of emerging viruses directly from HA gene sequence data and accuracy was doubled by including all substitutions causing antigenic changes over a model incorporating only the substitutions with the largest impact. The ability to quantify the phenotypic impact of specific amino acid substitutions should help refine emerging techniques that predict the evolution of virus populations from one year to the next, leading to stronger theoretical foundations for selection of candidate vaccine viruses. These techniques have great potential to be extended to other antigenically variable pathogens.

Identifying when past exposure to an infectious disease will protect against newly emerging strains is central to understanding the spread and the severity of epidemics, but the prediction of viral cross-protection remains an important unsolved problem. For foot-and-mouth disease virus (FMDV) research in particular, improved methods for predicting this cross-protection are critical for predicting the severity of outbreaks within endemic settings where multiple serotypes and subtypes commonly co-circulate, as well as for deciding whether appropriate vaccine(s) exist and how much they could mitigate the effects of any outbreak. To identify antigenic relationships and their predictors, we used linear mixed effects models to account for variation in pairwise cross-neutralization titres using only viral sequences and structural data. We identified those substitutions in surface-exposed structural proteins that are correlates of loss of cross-reactivity. These allowed prediction of both the best vaccine match for any single virus and the breadth of coverage of new vaccine candidates from their capsid sequences as effectively as or better than serology. Sub-sequences chosen by the model-building process all contained sites that are known epitopes on other serotypes. Furthermore, for the SAT1 serotype, for which epitopes have never previously been identified, we provide strong evidence – by controlling for phylogenetic structure – for the presence of three epitopes across a panel of viruses and quantify the relative significance of some individual residues in determining cross-neutralization. Identifying and quantifying the importance of sites that predict viral strain cross-reactivity not just for single viruses but across entire serotypes can help in the design of vaccines with better targeting and broader coverage. These techniques can be generalized to any infectious agents where cross-reactivity assays have been carried out. As the parameterization uses pre-existing datasets, this approach quickly and cheaply increases both our understanding of antigenic relationships and our power to control disease.

Identifying the major sources of risk in disease transmission is key to designing effective controls. However, understanding of transmission dynamics across species boundaries is typically poor, making the design and evaluation of controls particularly challenging for zoonotic pathogens. One such global pathogen is Escherichia coli O157, which causes a serious and sometimes fatal gastrointestinal illness. Cattle are the main reservoir for E. coli O157, and vaccines for cattle now exist. However, adoption of vaccines is being delayed by conflicting responsibilities of veterinary and public health agencies, economic drivers, and because clinical trials cannot easily test interventions across species boundaries, lack of information on the public health benefits. Here, we examine transmission risk across the cattle-human species boundary and show three key results. First, supershedding of the pathogen by cattle is associated with the genetic marker stx2. Second, by quantifying the link between shedding density in cattle and human risk, we show that only the relatively rare supershedding events contribute significantly to human risk. Third, we show that this finding has profound consequences for the public health benefits of the cattle vaccine. A naïve evaluation based on efficacy in cattle would suggest a 50% reduction in risk; however, because the vaccine targets the major source of human risk, we predict a reduction in human cases of nearly 85%. By accounting for nonlinearities in transmission across the human-animal interface, we show that adoption of these vaccines by the livestock industry could prevent substantial numbers of human E. coli O157 cases.zoonoses | cross-species transmission | 80-20 rule | one health