Combining precision and power to maximize performance: a case study of the woodpecker's neck

National audienc

Modelling, design and control of a bird neck using tensegrity mechanisms

International audienceIn birds, the neck exhibits remarkable performances and serves as a dextrous arm for performing various tasks. Accordingly, it is an interesting bioinspiration for designing new manipulators with enhanced performances. This paper proposes a preliminary bird neck model using several stacked tensegrity crossed bar mechanisms. It addresses several issues regarding kinetostatic and dynamic modelling, design and control

Anti-CRISPR Phages Cooperate to Overcome CRISPR-Cas Immunity

This is the final version of the article. Available from Elsevier via the DOI in this record.Some phages encode anti-CRISPR (acr) genes, which antagonize bacterial CRISPR-Cas immune systems by binding components of its machinery, but it is less clear how deployment of these acr genes impacts phage replication and epidemiology. Here, we demonstrate that bacteria with CRISPR-Cas resistance are still partially immune to Acr-encoding phage. As a consequence, Acr-phages often need to cooperate in order to overcome CRISPR resistance, with a first phage blocking the host CRISPR-Cas immune system to allow a second Acr-phage to successfully replicate. This cooperation leads to epidemiological tipping points in which the initial density of Acr-phage tips the balance from phage extinction to a phage epidemic. Furthermore, both higher levels of CRISPR-Cas immunity and weaker Acr activities shift the tipping points toward higher initial phage densities. Collectively, these data help elucidate how interactions between phage-encoded immune suppressors and the CRISPR systems they target shape bacteria-phage population dynamics.M.L. was supported by funding from the Wellcome Trust (https://wellcome.ac.uk) (109776/Z/15/Z), which was awarded to E.R.W. E.R.W. further acknowledges the Natural Environment Research Council (https://nerc.ukri.org) (NE/M018350/1), the BBSRC (BB/N017412/1), and the European Research Council (https://erc.europa.eu) (ERC-STG-2016-714478 - EVOIMMECH) for funding. S.v.H. acknowledges funding from the People Programme (Marie Curie Actions; https://ec.europa.eu/research/mariecurieactions/) of the European Union’s Horizon 2020 (REA grant agreement no. 660039) and from the BBSRC (BB/R010781/1). S.G. acknowledges funding (Visiting Professorship) from the Leverhulme Trust. A.B. acknowledges funding from the Royal Society. The authors thank Olivier Fradet for experimental contributions and Adair Borges and Joe Bondy-Denomy (UCSF) for providing DMS3mvir-AcrIF4 and phage JBD26

Exploitation of the cooperative behaviors of anti-CRISPR phages

This is the final version. Available on open access from Elsevier via the DOI in this recordBacteriophages encoding anti-CRISPR proteins (Acrs) must cooperate to overcome phage resistance mediated by the bacterial immune system CRISPR-Cas, where the first phage blocks CRISPR-Cas immunity in order to allow a second Acr phage to successfully replicate. However, in nature, bacteria are frequently not pre-immunized, and phage populations are often not clonal, exhibiting variations in Acr presence and strength. We explored how interactions between Acr phages and initially sensitive bacteria evolve, both in the presence and absence of competing phages lacking Acrs. We find that Acr phages benefit "Acr-negative" phages by limiting the evolution of CRISPR-based resistance and helping Acr-negative phages to replicate on resistant host sub-populations. These benefits depend on the strength of CRISPR-Cas inhibitors and result in strong Acrs providing smaller fitness advantages than weaker ones when Acr phages compete with Acr-negative phages. These results indicate that different Acr types shape the evolutionary dynamics and social interactions of phage populations in natural communities.European Commissio

Ecology and evolution of phages encoding anti-CRISPR proteins

This is the final version. Available from Elsevier via the DOI in this record. CRISPR-Cas are prokaryotic defence systems that provide protection against invasion by mobile genetic elements (MGE), including bacteriophages. MGE can overcome CRISPR-Cas defences by encoding anti-CRISPR (Acr) proteins. These proteins are produced in the early stages of the infection and inhibit the CRISPR-Cas machinery to allow phage replication. While research on Acr has mainly focused on their discovery, structure and mode of action, and their applications in biotechnology, the impact of Acr on the ecology of MGE as well as on the coevolution with their bacterial hosts only begins to be unravelled. In this review, we summarise our current understanding on the distribution of anti-CRISPR genes in MGE, the ecology of phages encoding Acr, and their coevolution with bacterial defence mechanisms. We highlight the need to use more diverse and complex experimental models to better understand the impact of anti-CRISPR in MGE-host interactions.Biotechnology & Biological Sciences Research Council (BBSRC)Biotechnology & Biological Sciences Research Council (BBSRC)Engineering and Physical Sciences Research Council (EPSRC)European Union’s Horizon 2020IdEx Université Paris Cit

3.5 The homing flight ring test: method for the assessment of sublethal doses of plant protection products on the honey bee in field conditions

International audienc

Evolution of central pattern generators for the control of a five-link bipedal walking mechanism

Central pattern generators (CPGs), with a basis is neurophysiological studies, are a type of neural network for the generation of rhythmic motion. While CPGs are being increasingly used in robot control, most applications are hand-tuned for a specific task and it is acknowledged in the field that generic methods and design principles for creating individual networks for a given task are lacking. This study presents an approach where the connectivity and oscillatory parameters of a CPG network are determined by an evolutionary algorithm with fitness evaluations in a realistic simulation with accurate physics. We apply this technique to a five-link planar walking mechanism to demonstrate its feasibility and performance. In addition, to see whether results from simulation can be acceptably transferred to real robot hardware, the best evolved CPG network is also tested on a real mechanism. Our results also confirm that the biologically inspired CPG model is well suited for legged locomotion, since a diverse manifestation of networks have been observed to succeed in fitness simulations during evolution.Comment: 11 pages, 9 figures; substantial revision of content, organization, and quantitative result

The effect of bacterial mutation rate on the evolution of CRISPR-Cas adaptive immunity

This is the final version. Available on open access from the Royal Society via the DOI in this recordData accessibility: Statistical analyses were carried out using the GraphPad Prism 7 software and R (v. 3.5.1). Raw data files from the experiments are available from the Dryad Digital Repository: http://dx.doi.org/10.5061/dryad.937s037CRISPR-Cas immune systems are present in around half of bacterial genomes. Given the specificity and adaptability of this immune mechanism, it is perhaps surprising that they are not more widespread. Recent insights into the requirement for specific host factors for the function of some CRISPR-Cas subtypes, as well as the negative epistasis between CRISPR-Cas and other host genes, have shed light on potential reasons for the partial distribution of this immune strategy in bacteria. In this study, we examined how mutations in the bacterial mismatch repair system, which are frequently observed in natural and clinical isolates and cause elevated host mutation rates, influence the evolution of CRISPR-Cas-mediated immunity. We found that hosts with a high mutation rate very rarely evolved CRISPR-based immunity to phage compared to wild-type hosts. We explored the reason for this effect and found that the higher frequency at which surface mutants pre-exist in the mutator host background causes them to rapidly become the dominant phenotype under phage infection. These findings suggest that natural variation in bacterial mutation rates may, therefore, influence the distribution of CRISPR-Cas adaptive immune systems. This article is part of a discussion meeting issue 'The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems'

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Exploitation of the cooperative behaviours of anti-CRISPR phages

Bacteriophages encoding anti-CRISPR proteins (Acrs) must cooperate to overcome phage resistance mediated by the bacterial immune system CRISPR-Cas, where the first phage blocks CRISPR-Cas immunity in order to allow a second Acr phage to successfully replicate. However, in nature, bacteria are frequently not pre-immunized, and phage populations are often not clonal, exhibiting variations in Acr presence and strength. We explored how interactions between Acr phages and initially sensitive bacteria evolve, both in the presence and absence of competing phages lacking Acrs. We find that Acr phages benefit “Acr-negative” phages by limiting the evolution of CRISPR-based resistance and helping Acr-negative phages to replicate on resistant host sub-populations. These benefits depend on the strength of CRISPR-Cas inhibitors and result in strong Acrs providing smaller fitness advantages than weaker ones when Acr phages compete with Acr-negative phages. These results indicate that different Acr types shape the evolutionary dynamics and social interactions of phage populations in natural communities