Correction: Structure of the Malaria Antigen AMA1 in Complex with a Growth-Inhibitory Antibody

Identifying functionally critical regions of the malaria antigen AMA1 (apical membrane antigen 1) is necessary to understand the significance of the polymorphisms within this antigen for vaccine development. The crystal structure of AMA1 in complex with the Fab fragment of inhibitory monoclonal antibody 1F9 reveals that 1F9 binds to the AMA1 solvent-exposed hydrophobic trough, confirming its importance. 1F9 uses the heavy and light chain complementarity-determining regions (CDRs) to wrap around the polymorphic loops adjacent to the trough, but uses a ridge of framework residues to bind to the hydrophobic trough. The resulting 1F9-AMA1–combined buried surface of 2,470 Å2 is considerably larger than previously reported Fab–antigen interfaces. Mutations of polymorphic AMA1 residues within the 1F9 epitope disrupt 1F9 binding and dramatically reduce the binding of affinity-purified human antibodies. Moreover, 1F9 binding to AMA1 is competed by naturally acquired human antibodies, confirming that the 1F9 epitope is a frequent target of immunological attack

Clean subglacial access:Prospects for future deep hot-water drilling

Accessing and sampling subglacial environments deep beneath the Antarctic Ice Sheet presents several challenges to existing drilling technologies. With over half of the ice sheet believed to be resting on a wet bed, drilling down to this environment must conform to international agreements on environmental stewardship and protection, making clean hot-water drilling the most viable option. Such a drill, and its water recovery system, must be capable of accessing significantly greater ice depths than previous hot-water drills, and remain fully operational after connecting with the basal hydrological system. The Subglacial Lake Ellsworth (SLE) project developed a comprehensive plan for deep (greater than 3000 m) subglacial lake research, involving the design and development of a clean deep-ice hot-water drill. However, during fieldwork in December 2012 drilling was halted after a succession of equipment issues culminated in a failure to link with a subsurface cavity and abandonment of the access holes. The lessons learned from this experience are presented here. Combining knowledge gained from these lessons with experience from other hot-water drilling programmes, and recent field testing, we describe the most viable technical options and operational procedures for future clean entry into SLE and other deep subglacial access targets.</p

Subglacial lakes and hydrology across the Ellsworth Subglacial Highlands, West Antarctica

Subglacial water plays an important role in ice sheet dynamics and stability. Subglacial lakes are often located at the onset of ice streams and have been hypothesised to enhance ice flow downstream by lubricating the ice–bed interface. The most recent subglacial-lake inventory of Antarctica mapped nearly 400 lakes, of which ∼ 14 % are found in West Antarctica. Despite the potential importance of subglacial water for ice dynamics, there is a lack of detailed subglacial-water characterisation in West Antarctica. Using radio-echo sounding data, we analyse the ice–bed interface to detect subglacial lakes. We report 33 previously uncharted subglacial lakes and present a systematic analysis of their physical properties. This represents a ∼ 40 % increase in subglacial lakes in West Antarctica. Additionally, a new digital elevation model of basal topography of the Ellsworth Subglacial Highlands was built and used to create a hydropotential model to simulate the subglacial hydrological network. This allows us to characterise basal hydrology, determine subglacial water catchments and assess their connectivity. We show that the simulated subglacial hydrological catchments of the Rutford Ice Stream, Pine Island Glacier and Thwaites Glacier do not correspond to their ice surface catchments

Biotic and abiotic factors influencing forage fish and pelagic nekton community in the Columbia River plume (USA) throughout the upwelling season 1999–2009

Large river plumes modify coastal environments and can impact production across multiple trophic levels. From 1999 to 2009, the assemblages of forage fish, predator fish, and other pelagic nekton were monitored in coastal waters associated with the Columbia River plume. Surveys were conducted at night to target vertically migrating species, and community structure evaluated to better understand ecological interactions. Distinct inshore and offshore communities were identified during spring and summer that were correlated with ocean temperature, salinity, plume volume, and upwelling intensity. Resident euryhaline forage fish species, such as smelts, anchovy, herring, market squid, juvenile salmon, and spiny dogfish, showed a high affinity for inshore habitat and the lower salinity plume during spring. Highly migratory species, such as sardine, piscivorous hake, sharks, and mackerels, were associated with warmer, saltier waters offshore, during strong upwelling periods in summer. Overall, our study of pelagic nekton revealed that temporal dynamics in abundance and community composition were associated with seasonal abiotic phenomenon, but not interannual, large-scale oceanographic processes. Forage fish assemblages differed seasonally and spatially from the assemblages of major piscivorous predators. This finding suggests a potential role of the plume as refuge for forage fish from predation by piscivorous fish in the northern California Current.Keywords: Predator fish, Columbia River plume, California current, Community analysis, Forage fishKeywords: Predator fish, Columbia River plume, California current, Community analysis, Forage fis

Preparation of amino-substituted indenes and 1,4-dihydronaphthalenes using a one-pot multireaction approach: total synthesis of oxybenzo[c]phenanthridine alkaloids

Allylic trichloroacetimidates bearing a 2-vinyl or 2-allylaryl group have been designed as substrates for a one-pot, two-step multi-bond-forming process leading to the general preparation of aminoindenes and amino-substituted 1,4-dihydronaphthalenes. The synthetic utility of the privileged structures formed from this one-pot process was demonstrated with the total synthesis of four oxybenzo[c]phenanthridine alkaloids, oxychelerythrine, oxysanguinarine, oxynitidine, and oxyavicine. An intramolecular biaryl Heck coupling reaction, catalyzed using the Hermann–Beller palladacycle was used to effect the key step during the synthesis of the natural products

Housing Affordability, Tenure and Mental Health in Australia and the United Kingdom: A Comparative Panel Analysis

The paper contributes insights into the role of tenure in modifying the relationship between housing affordability and health, using a cross-national comparison of similar post-industrial nations ? Australia and the United Kingdom ? with different tenure structures. The paper utilises longitudinal data from the Household, Income and Labour Dynamics in Australia Survey (HILDA) and British Household Panel Survey (BHPS) to examine change in the mental health of individuals associated with housing becoming unaffordable and considers modification by tenure. We present evidence that the role of tenure in the relationship between housing and health is context dependent and should not be unthinkingly generalised across nations. These findings suggest that the UK housing context offers a greater level of protection to tenants living in unaffordable housing when compared with Australia, and this finds expression in the mental health of the two populations. We conclude that Australian governments could improve the mental health of their economically vulnerable populations through more supportive housing policies

Microbiome profiling by Illumina sequencing of combinatorial sequence-tagged PCR products

We developed a low-cost, high-throughput microbiome profiling method that uses combinatorial sequence tags attached to PCR primers that amplify the rRNA V6 region. Amplified PCR products are sequenced using an Illumina paired-end protocol to generate millions of overlapping reads. Combinatorial sequence tagging can be used to examine hundreds of samples with far fewer primers than is required when sequence tags are incorporated at only a single end. The number of reads generated permitted saturating or near-saturating analysis of samples of the vaginal microbiome. The large number of reads al- lowed an in-depth analysis of errors, and we found that PCR-induced errors composed the vast majority of non-organism derived species variants, an ob- servation that has significant implications for sequence clustering of similar high-throughput data. We show that the short reads are sufficient to assign organisms to the genus or species level in most cases. We suggest that this method will be useful for the deep sequencing of any short nucleotide region that is taxonomically informative; these include the V3, V5 regions of the bac- terial 16S rRNA genes and the eukaryotic V9 region that is gaining popularity for sampling protist diversity.Comment: 28 pages, 13 figure

Participative decision making and the sharing of benefits: laws, ethics, and data protection for building extended global communities

Transdisciplinary and cross-cultural cooperation and collaboration are needed to build extended, densely interconnected information resources. These are the prerequisites for the successful implementation and execution of, for example, an ambitious monitoring framework accompanying the post-2020 Global Biodiversity Framework (GBF) of the Convention on Biological Diversity (CBD; SCBD 2021). Data infrastructures that meet the requirements and preferences of concerned communities can focus and attract community involvement, thereby promoting participatory decision making and the sharing of benefits. Community acceptance, in turn, drives the development of the data resources and data use. Earlier this year, the alliance for biodiversity knowledge (2021a) conducted forum-based consultations seeking community input on designing the next generation of digital specimen representations and consequently enhanced infrastructures. The multitudes of connections that arise from extending the digital specimen representations through linkages in all “directions” will form a powerful network of information for research and application. Yet, with the power of an extended, accessible data network comes the responsibility to protect sensitive information (e.g., the locations of threatened populations, culturally context-sensitive traditional knowledge, or businesses’ fundamental data and infrastructure assets). In addition, existing legislation regulates access and the fair and equitable sharing of benefits. Current negotiations on ‘Digital Sequence Information’ under the CBD suggest such obligations might increase and become more complex in the context of extensible information networks. For example, in the case of data and resources funded by taxpayers in the EU, such access should follow the general principle of being “as open as possible; as closed as is legally necessary” (cp. EC 2016). At the same time, the international regulations of the CBD Nagoya Protocol (SCBD 2011) need to be taken into account. Summarizing main outcomes from the consultation discussions in the forum thread “Meeting legal/regulatory, ethical and sensitive data obligations” (alliance for biodiversity knowledge 2021b), we propose a framework of ten guidelines and functionalities to achieve community building and drive application: Substantially contribute to the conservation and protection of biodiversity (cp. EC 2020). Use language that is CBD conformant. Show the importance of the digital and extensible specimen infrastructure for the continuing design and implementation of the post-2020 GBF, as well as the mobilisation and aggregation of data for its monitoring elements and indicators. Strive to openly publish as much data and metadata as possible online. Establish a powerful and well-thought-out layer of user and data access management, ensuring security of ‘sensitive data’. Encrypt data and metadata where necessary at the level of an individual specimen or digital object; provide access via digital cryptographic keys. Link obligations, rights and cultural information regarding use to the digital key (e.g. CARE principles (Carroll et al. 2020), Local Context-labels (Local Contexts 2021), licenses, permits, use and loan agreements, etc.). Implement a transactional system that records every transaction. Amplify workforce capacity across the digital realm, its work areas and workflows. Do no harm (EC 2020): Reduce the social and ecological footprint of the implementation, aiming for a long-term sustainable infrastructure across its life-cycle, including development, implementation and management stages. Balancing the needs for open access, as well as protection, accountability and sustainability, the framework is designed to function as a robust interface between the (research) infrastructure implementing the extensible network of digital specimen representations, and the myriad of applications and operations in the real world. With the legal, ethical and data protection layers of the framework in place, the infrastructure will provide legal clarity and security for data providers and users, specifically in the context of access and benefit sharing under the CBD and its Nagoya Protocol. Forming layers of protection, the characteristics and functionalities of the framework are envisioned to be flexible and finely-grained, adjustable to fulfill the needs and preferences of a wide range of stakeholders and communities, while remaining focused on the protection and rights of the natural world. Respecting different value systems and national policies, the framework is expected to allow a divergence of views to coexist and balance differing interests. Thus, the infrastructure of the digital extensible specimen network is fair and equitable to many providers and users. This foundation has the capacity and potential to bring together the diverse global communities using, managing and protecting biodiversity

Twenty-eight divergent polysaccharide loci specifying within- and amongst-strain capsule diversity in three strains of Bacteroides fragilis

Comparison of the complete genome sequence of Bacteroides fragilis 638R, originally isolated in the USA, was made with two previously sequenced strains isolated in the UK (NCTC 9343) and Japan (YCH46). The presence of 10 loci containing genes associated with polysaccharide (PS) biosynthesis, each including a putative Wzx flippase and Wzy polymerase, was confirmed in all three strains, despite a lack of cross-reactivity between NCTC 9343 and 638R surface PS-specific antibodies by immunolabelling and microscopy. Genomic comparisons revealed an exceptional level of PS biosynthesis locus diversity. Of the 10 divergent PS-associated loci apparent in each strain, none is similar between NCTC 9343 and 638R. YCH46 shares one locus with NCTC 9343, confirmed by mAb labelling, and a second different locus with 638R, making a total of 28 divergent PS biosynthesis loci amongst the three strains. The lack of expression of the phase-variable large capsule (LC) in strain 638R, observed in NCTC 9343, is likely to be due to a point mutation that generates a stop codon within a putative initiating glycosyltransferase, necessary for the expression of the LC in NCTC 9343. Other major sequence differences were observed to arise from different numbers and variety of inserted extra-chromosomal elements, in particular prophages. Extensive horizontal gene transfer has occurred within these strains, despite the presence of a significant number of divergent DNA restriction and modification systems that act to prevent acquisition of foreign DNA. The level of amongst-strain diversity in PS biosynthesis loci is unprecedented