Rational design of a (S)-selective-transaminase for asymmetric synthesis of (1S)-1-(1,1′-biphenyl-2-yl)ethanamine

Amine transaminases offer an environmentally sustainable synthesis route for the production of pure chiral amines. However, their catalytic efficiency toward bulky ketone substrates is greatly limited by steric hindrance and therefore presents a great challenge for industrial synthetic applications. We hereby report an example of rational transaminase enzyme design to help alleviate these challenges. Starting from the Vibrio fluvialis amine transaminase that has no detectable catalytic activity toward the bulky aromatic ketone 2-acetylbiphenyl, we employed a rational design strategy combining in silico and in vitro studies to engineer the transaminase enzyme with a minimal number of mutations, achieving an high catalytic activity and high enantioselectivity. We found that, by introducing two mutations W57G/R415A, detectable enzyme activity was achieved. The rationally designed variant, W57F/R88H/V153S/K163F/I259M/R415A/V422A, showed an improvement in reaction rate by more than 1716-fold toward the bulky ketone under study, producing the corresponding enantiomeric pure (S)-amine (enantiomeric excess (ee) value of >99%)

Learning from our peer educators: a guide for integrating and reflecting participatory youth research in the A+ assessment country case studies

This guide is a tool that can be used by Member Associations and other organizations to plan and implement future participatory research and/or programme assessments with young people. It covers the case-study component of the A+ programme global assessment and covers the methodology, agenda, approaches and exercises that the assessment team members used during four country visits. It covers face-toface interaction and research with different stakeholders at country level, The focus during the case-study visits was on capturing youth perspectives and generating Member Association support and initial capacity for using a participatory evaluation approach, involving youth-led research, analysis and discussion

Pollinating insects: what do they mean to people and why does it matter?

1. People value pollinating insects, and especially bees, in a wide range of different ways: as beautiful or fascinating creatures; as providers of goods; as objects of stewardship; as participants in a greater, interconnected whole – in which humans also participate; and as creatures with lives and characters. 2. An understanding of pollinators as creative connectors, sustaining and creating life by moving from plant to plant, is particularly powerful. Pollinators prompt people to think about nature as an interconnected whole, in which they too participate; and can unlock feelings of wonder, awe, groundedness, concern, responsibility, and nostalgia. 3. Social and cultural values provide a powerful resource for effective communications, a store of pre-existing meanings and associations that can be used to frame messages. Communications about pollinators would resonate more powerfully if they framed pollinators as creative connecters, emblematic of the interconnected and interdependent nature of ecosystems. By contrast, communications which focus on what pollinators do for us (e.g. pollination framed as an ‘ecosystem service’) are rational but unemotional. 4. Communications drawing on these insights should: • Highlight first and foremost the critical role played by pollinators as creative connectors in a greater, interconnected whole • Acknowledge our dependency on that greater interconnected whole, but also our responsibilities as participants in it • Be willing to embrace and use non-scientific language, ideas and tonalities in talking about both pollinators and the interconnected whole of which they are part, for example: o spiritual/religious language in evoking feelings of awe and wonder at the greater interconnected whole o evocations of an idealised, traditional way of life, and the possibilities of reconnecting in some small way o metaphorical characterisations of pollinators as spreading life and love • Recognise that we face choices about the environment not just as individuals, but as a society; that people see evidence of our society as a whole making the wrong choices; and that the actions of any body seeking to campaign about pollinators will speak as loudly, if not louder, than the messages it promotes • Emphasise – in messages, but also in developing the case for a campaign – the link between the holistic perspective, subjective wellbeing, and reconnection: o reconnection with nature: the consolation of knowing that one has a place in an enduring, greater whole, and a responsibility to play a positive role in that whole o reconnection with self: the experience of a moment of self-aware contemplation in contrast to the day-to-day stresses of life o reconnection with history: a sense of contact with an idealised traditional way of life 5. If developed effectively, such campaigns will contribute to many of the key actions in the National Pollinator Strategy, and in particular actions relating to “supporting pollinators across towns, cities and the countryside” (including encouraging the public to take action) and to “raising awareness of what pollinators need to survive and thrive”. 6. Because they prompt people to think about and respond emotionally to the interconnectedness of nature, pollinators framed as creative connectors could play an important role in communications seeking to increase awareness and change behaviour in relation to a much wider range of policies and approaches which relate to the connectedness of nature: for example, maintaining wider natural connectivity, protecting biodiversity, and ensuring environmental resilience through approaches such as those relating to the concept of landscape level conservation. As such, pollinators could play an important role in delivery of the 25-year plan for the environment, and in particular in efforts to increase public engagement. 7. Compared to other pollinating insects, bees occupy a central position in our culture. The ‘popular bee’ is not a real insect, but a product of a blurring of species, idealisation of the past, ignorance of the diversity of pollinators and, often, a shaky grasp on what pollination actually means. It is, however, a very meaningful and valued insect, and as such can serve as a flagship for communications in all of the above areas. 8. In terms of wider policy and decision-making, this research offers a potential model of how to create an evidence-based catalogue of social and cultural values. The development of such an evidence-based catalogue, using a mix of interpretative and participatory methods to explore how, and in what capacities, people can and do value objects of interest, should be an essential pre-requisite for robust valuation across a wide range of natural environment policy areas, but in practice is rarely undertaken. 9. Some types of social and cultural value can be captured through economic valuation: either through monetisation or through the inclusion of non-monetised criteria in multi-criteria analysis approaches. To do this, however, it is essential that data-gathering tools assess the right things: e.g. that willingness-to-pay questions frame the object of value in the right capacity and from the right perspective. 10. It may be more practical and/or appropriate to take account of some types of social and cultural value in policy and decision-making through other mechanisms, such as public consultation, political representation, or open policy-making. It may not be possible to monetise some kinds of value. In other cases, the effort involved in economic valuation may be disproportionate. If alternative mechanisms are not used, there is a risk that certain kinds of social and cultural value, or certain objects of value, are systematically overlooked. 11. Key levers to ensure that these alternative mechanisms are used effectively include: • Align policy frameworks – for example, set priorities and requirements in overarching national policies which ensure key social and cultural values or objects of value are taken into account. • Provide contexts – for example, create public consultation contexts in which certain kinds of value will be surfaced, or objects of value considered. • Improve processes – e.g. ensure consultation questions frame objects of value in ways that invite the articulate of key values. 12. An evidence-based catalogue of social and cultural values also provides a basis on which to anticipate risks and opportunities arising from changes in public opinion. Social and cultural values may be widely available within a society or culture but not, at any given moment, widely used. It is not always possible to predict how patterns of use will change in response to policies (e.g. forest privatisation, neonicotinoid pesticide policy); but an evidence-based understanding of underlying social and cultural values makes it possible to develop and explore scenarios of how they could change and develop responses accordingly

Snipe taxonomy based on vocal and non-vocal sound displays: the South American Snipe is two species

We analysed breeding sounds of the two subspecies of South American Snipe Gallinago paraguaiae paraguaiae and Gallinago paraguaiae magellanica to determine whether they might be different species: loud vocalizations given on the ground, and the tail‐generated Winnow given in aerial display. Sounds of the two taxa differ qualitatively and quantitatively. Both taxa utter two types of ground call. In G. p. paraguaiae, the calls are bouts of identical sound elements repeated rhythmically and slowly (about five elements per second (Hz)) or rapidly (about 11 Hz). One call of G. p. magellanica is qualitatively similar to those of G. p. paraguaiae but sound elements are repeated more slowly (about 3 Hz). However, its other call type differs strikingly: it is a bout of rhythmically repeated sound couplets, each containing two kinds of sound element. The Winnow of G. p. paraguaiae is a series of sound elements that gradually increase in duration and energy; by contrast, that of G. p. magellanica has two or more kinds of sound element that roughly alternate and are repeated as sets, imparting a stuttering quality. Sounds of the related Puna Snipe (Gallinago andina) resemble but differ quantitatively from those of G. p. paraguaiae. Differences in breeding sounds of G. p. paraguaiae and G. p. magellanica are strong and hold throughout their geographical range. Therefore we suggest that the two taxa be considered different species: G. paraguaiae east of the Andes in much of South America except Patagonia, and G. magellanica in central and southern Chile, Argentina east of the Andes across Patagonia, and Falklands/Malvinas.Fil: Miller, Edward H.. Memorial University Of Newfoundland; CanadáFil: Areta, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Bio y Geociencias del NOA. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Museo de Ciencias Naturales. Instituto de Bio y Geociencias del NOA; ArgentinaFil: Jaramillo, Alvaro. San Francisco Bay Bird Observatory; Estados UnidosFil: Imberti, Santiago. Asociación Ambiente Sur, Rio Gallegos; ArgentinaFil: Matus, Ricardo. Kilómetro 7 Sur; Chil

Translocation of Threatened New Zealand Falcons to Vineyards Increases Nest Attendance, Brooding and Feeding Rates

Anthropogenic landscapes can be rich in resources, and may in some cases provide potential habitat for species whose natural habitat has declined. We used remote videography to assess whether reintroducing individuals of the threatened New Zealand falcon Falco novaeseelandiae into a highly modified agricultural habitat affected the feeding rates of breeding falcons or related breeding behavior such as nest attendance and brooding rates. Over 2,800 recording hours of footage were used to compare the behavior of falcons living in six natural nests (in unmanaged, hilly terrain between 4 km and 20 km from the nearest vineyard), with that of four breeding falcon pairs that had been transported into vineyards and nested within 500 m of the nearest vineyard. Falcons in vineyard nests had higher feeding rates, higher nest attendance, and higher brooding rates. As chick age increased, parents in vineyard nests fed chicks a greater amount of total prey and larger prey items on average than did parents in hill nests. Parents with larger broods brought in larger prey items and a greater total sum of prey biomass. Nevertheless, chicks in nests containing siblings received less daily biomass per individual than single chicks. Some of these results can be attributed to the supplementary feeding of falcons in vineyards. However, even after removing supplementary food from our analysis, falcons in vineyards still fed larger prey items to chicks than did parents in hill nests, suggesting that the anthropogenic habitat may be a viable source of quality food. Although agricultural regions globally are rarely associated with raptor conservation, these results suggest that translocating New Zealand falcons into vineyards has potential for the conservation of this species

The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC

Invasive mammal eradication on islands results in substantial conservation gains

More than US$21 billion is spent annually on biodiversity conservation. Despite their importance for preventing or slowing extinctions and preserving biodiversity, conservation interventions are rarely assessed systematically for their global impact. Islands house a disproportionately higher amount of biodiversity compared with mainlands, much of which is highly threatened with extinction. Indeed, island species make up nearly two-thirds of recent extinctions. Islands therefore are critical targets of conservation. We used an extensive literature and database review paired with expert interviews to estimate the global benefits of an increasingly used conservation action to stem biodiversity loss: eradication of invasive mammals on islands. We found 236 native terrestrial insular faunal species (596 populations) that benefitted through positive demographic and/or distributional responses from 251 eradications of invasive mammals on 181 islands. Seven native species (eight populations) were negatively impacted by invasive mammal eradication. Four threatened species had their International Union for the Conservation of Nature (IUCN) Red List extinction-risk categories reduced as a direct result of invasive mammal eradication, and no species moved to a higher extinction-risk category. We predict that 107 highly threatened birds, mammals, and reptiles on the IUCN Red List—6% of all these highly threatened species—likely have benefitted from invasive mammal eradications on islands. Because monitoring of eradication outcomes is sporadic and limited, the impacts of global eradications are likely greater than we report here. Our results highlight the importance of invasive mammal eradication on islands for protecting the world's most imperiled fauna.This is the publisher’s final pdf. The published article is copyrighted by the National Academy of Sciences and can be found at: http://www.pnas.org/Keywords: island, restoration, invasive species, conservation, eradicationKeywords: island, restoration, invasive species, conservation, eradicatio

Recurrent SARS-CoV-2 mutations in immunodeficient patients

Long-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in immunodeficient patients are an important source of variation for the virus but are understudied. Many case studies have been published which describe one or a small number of long-term infected individuals but no study has combined these sequences into a cohesive dataset. This work aims to rectify this and study the genomics of this patient group through a combination of literature searches as well as identifying new case series directly from the COVID-19 Genomics UK (COG-UK) dataset. The spike gene receptor-binding domain and N-terminal domain (NTD) were identified as mutation hotspots. Numerous mutations associated with variants of concern were observed to emerge recurrently. Additionally a mutation in the envelope gene, T30I was determined to be the second most frequent recurrently occurring mutation arising in persistent infections. A high proportion of recurrent mutations in immunodeficient individuals are associated with ACE2 affinity, immune escape, or viral packaging optimisation.There is an apparent selective pressure for mutations that aid cell–cell transmission within the host or persistence which are often different from mutations that aid inter-host transmission, although the fact that multiple recurrent de novo mutations are considered defining for variants of concern strongly indicates that this potential source of novel variants should not be discounted. © The Author(s) 2022. Published by Oxford University Press

Spatial growth rate of emerging SARS-CoV-2 lineages in England, September 2020-December 2021

This paper uses a robust method of spatial epidemiological analysis to assess the spatial growth rate of multiple lineages of SARS-CoV-2 in the local authority areas of England, September 2020–December 2021. Using the genomic surveillance records of the COVID-19 Genomics UK (COG-UK) Consortium, the analysis identifies a substantial (7.6-fold) difference in the average rate of spatial growth of 37 sample lineages, from the slowest (Delta AY.4.3) to the fastest (Omicron BA.1). Spatial growth of the Omicron (B.1.1.529 and BA) variant was found to be 2.81× faster than the Delta (B.1.617.2 and AY) variant and 3.76× faster than the Alpha (B.1.1.7 and Q) variant. In addition to AY.4.2 (a designated variant under investigation, VUI-21OCT-01), three Delta sublineages (AY.43, AY.98 and AY.120) were found to display a statistically faster rate of spatial growth than the parent lineage and would seem to merit further investigation. We suggest that the monitoring of spatial growth rates is a potentially valuable adjunct to outbreak response procedures for emerging SARS-CoV-2 variants in a defined population