Proceedings of the 4^thBEAT-PCD Conference and 5^thPCD Training School

Primary ciliary dyskinesia (PCD) is an inherited ciliopathy leading to chronic suppurative lung disease, chronic rhinosinusitis, middle ear disease, sub-fertility and situs abnormalities. As PCD is rare, it is important that scientists and clinicians foster international collaborations to share expertise in order to provide the best possible diagnostic and management strategies. ‘Better Experimental Approaches to Treat Primary Ciliary Dyskinesia’ (BEAT-PCD) is a multidisciplinary network funded by EU COST Action (BM1407) to coordinate innovative basic science and clinical research from across the world to drive advances in the field. The fourth and final BEAT-PCD Conference and fifth PCD Training School were held jointly in March 2019 in Poznan, Poland. The varied program of plenaries, workshops, break-out sessions, oral and poster presentations were aimed to enhance the knowledge and skills of delegates, whilst also providing a collaborative platform to exchange ideas. In this final BEAT-PCD conference we were able to build upon programmes developed throughout the lifetime of the COST Action. These proceedings report on the conference, highlighting some of the successes of the BEAT-PCD programme

De novo designed peptide and protein hairpins self‐assemble into sheets and nanoparticles

AFM, TEM, fluorescence microscopy image files and spectral data published in DOI:10.1002/smll.202100472. Preprint of this is available at bioRxiv DOI:10.1101/2020.08.14.25146

Analysis of landrace cultivation in Europe: A means to support in situ conservation of crop diversity

During the last century, the progressive substitution of landraces with modern, high yielding varieties, led to a dramatic reduction of in situ conserved crop diversity in Europe. Nowadays there is limited and scattered information on where landraces are cultivated. To fill this gap and lay the groundwork for a regional landrace in situ conservation strategy, information on more than 19,335 geo-referenced landrace cultivation sites were collated from 14 European countries. According to collected data, landraces of 141 herbaceous and 48 tree species are cultivated across Europe: Italy (107 species), Greece (93), Portugal (45) and Spain (44) hold the highest numbers. Common bean, onion, tomato, potato and apple are the species of main interest in the covered countries. As from collected data, about 19.8% of landrace cultivation sites are in protected areas of the Natura 2000 network. We also got evidence that 16.7% and 19.3% of conservation varieties of agricultural species and vegetables are currently cultivated, respectively. Results of the GIS analysis allowed the identification of 1261 cells (25 km × 25 km) including all the cultivation sites, distributed across all European biogeographical regions. Data of this study constitute the largest ever produced database of in situ-maintained landraces and the first attempt to create an inventory for the entire Europe. The availability of such resource will serve for better planning of actions and development of policies to protect landraces and foster their use

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

Background Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. Methods In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in both groups continued to receive other therapies required to manage their condition. Participants, study staff, and investigators were masked to the study assignment. The primary outcome was the 7-point WHO ordinal scale for clinical status at day 29 after random assignment. The intention-to-treat population included all patients who were randomly assigned and met the enrolment criteria. The safety population included all participants who received at least one dose of study medication. This study was registered with the ISRCTN registry, ISRCTN30564012. Findings Between June 5, 2020, and Jan 25, 2021, 406 patients were randomly assigned to brensocatib or placebo; 192 (47·3%) to the brensocatib group and 214 (52·7%) to the placebo group. Two participants were excluded after being randomly assigned in the brensocatib group (214 patients included in the placebo group and 190 included in the brensocatib group in the intention-to-treat population). Primary outcome data was unavailable for six patients (three in the brensocatib group and three in the placebo group). Patients in the brensocatib group had worse clinical status at day 29 after being randomly assigned than those in the placebo group (adjusted odds ratio 0·72 [95% CI 0·57–0·92]). Prespecified subgroup analyses of the primary outcome supported the primary results. 185 participants reported at least one adverse event; 99 (46%) in the placebo group and 86 (45%) in the brensocatib group. The most common adverse events were gastrointestinal disorders and infections. One death in the placebo group was judged as possibly related to study drug. Interpretation Brensocatib treatment did not improve clinical status at day 29 in patients hospitalised with COVID-19. Funding Sponsored by the University of Dundee and supported through an Investigator Initiated Research award from Insmed, Bridgewater, NJ; STOP-COVID19 trial

Eragrostis curvula (Schrad.) Nees. complex pastures in southern New South Wales, Australia : a comparison with Medicago sativa L. and Phalaris aquatica L. pastures under rotational grazing

A grazing experiment conducted in Wagga Wagga (New South Wales) from September 1993 to September 1998 compared the productivity of pastures containing 3 palatable types of summer-active Eragrostis curvula complex, with pastures containing either Medicago sativa or Phalaris aquatica. Issues relating to the management of E. curvula pastures were also investigated. Herbage growth rates of the P. aquatica and M. sativa pastures were highest in winter and spring; E. curvula pastures were most productive in summer and autumn. Stocking rates equivalent to 30–40 dry sheep were carried by the pastures during their growing seasons. Throughout the study, the pastures were dominated by their respective sown perennial species, however, a suite of desirable and undesirable annual grasses and annual legumes usually contributed >20% of total herbage mass in spring. The P. aquatica pasture contained a higher proportion of weedy species than the other pastures, especially C4 grasses and broadleafed species, and towards the end of the experiment it was also invaded by several native perennial grasses. Overall, the wool yield from the M. sativa pasture was 0.5–1.0 kg/animal.year higher than the other pastures. Management to minimise herbage accumulation on the E. curvula pastures was a key issue, and provided that pastures were grazed heavily, this was achieved by the rotational grazing strategy used in the experiment. It was concluded that palatable varieties of E. curvula have a useful and complementary role as perennial pastures in southern Australia. By increasing herbage availability in summer and autumn, E. curvula may improve management flexibility for a wide range of pastures that are commonly grown on farms

Eragrostis curvula (Schrad.) Nees. complex pastures in southern New South Wales, Australia : a comparison of Eragrostis curvula cv. Consol and Medicago sativa L. cv. Nova under intensive rotational management

The productivity, carrying capacity and liveweight performance of wether sheep grazing pastures of Eragrostis curvula cv. Consol and Medicago sativa cv. Nova, which were also sown with annual grasses and Trifolium subterraneum, were compared under an intensive 4-paddock rotational grazing regime in a ‘put-and-take’ grazing experiment at Wagga Wagga, New South Wales from November 1993 to August 1996. The productivity of the pastures was broadly similar, with production peaks of >1000 kg/ha in winter and >3000 kg/ha in spring and summer in paddocks that had been spelled for 6 weeks. Although annual species contributed a high proportion of the total herbage mass in spring, over the remainder of the year, both pastures were dominated by their respective perennials. E. curvula maintained an average plant density of approximately 20 plants/m2. The density of M. sativa declined noticeably during the 3 years, and at the end of the experiment M. sativa plants in 1 replicate of the experiment were killed by rising groundwater and dryland salinity. The long-term average stocking rate of E. curvula and M. sativa pastures were similar (12.1 v. 12.5 sheep/ha) and both pastures were capable of sustaining high stocking rates for lengthy periods in spring and summer. Sheep grazing M. sativa tended to be heavier than animals grazing E. curvula, and they produced, on average, 1.1 kg (or 21%) more wool. However, M. sativa was more difficult to establish and its costs for weed and insect control were higher. Therefore, although it was more productive, it might not have been the most economically viable of the 2 pastures. The implications of the findings were discussed within a whole-farm context and it was concluded that E. curvula has a complimentary role to M. sativa for sowing on landscapes and in situations to which M. sativa is poorly adapted