Synthesis and structural characterization of piperazino-modified DNA that favours hybridization towards DNA over RNA

We report the synthesis of two C4′-modified DNA analogues and characterize their structural impact on dsDNA duplexes. The 4′-C-piperazinomethyl modification stabilizes dsDNA by up to 5°C per incorporation. Extension of the modification with a butanoyl-linked pyrene increases the dsDNA stabilization to a maximum of 9°C per incorporation. Using fluorescence, ultraviolet and nuclear magnetic resonance (NMR) spectroscopy, we show that the stabilization is achieved by pyrene intercalation in the dsDNA duplex. The pyrene moiety is not restricted to one intercalation site but rather switches between multiple sites in intermediate exchange on the NMR timescale, resulting in broad lines in NMR spectra. We identified two intercalation sites with NOE data showing that the pyrene prefers to intercalate one base pair away from the modified nucleotide with its linker curled up in the minor groove. Both modifications are tolerated in DNA:RNA hybrids but leave their melting temperatures virtually unaffected. Fluorescence data indicate that the pyrene moiety is residing outside the helix. The available data suggest that the DNA discrimination is due to (i) the positive charge of the piperazino ring having a greater impact in the narrow and deep minor groove of a B-type dsDNA duplex than in the wide and shallow minor groove of an A-type DNA:RNA hybrid and (ii) the B-type dsDNA duplex allowing the pyrene to intercalate and bury its apolar surface

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Ecological Consequences of Animal Migration : Prey Partial Migration Affects Predator Ecology and Prey Communities

Patterns of animal migration and the ecological forces that shape them have been studied for centuries. Yet ecological impacts caused by the migration, such as altered predator–prey interactions and effects on community structure, remain poorly understood. This is to a large extent due to the scarcity of naturally replicated migration systems with negative controls, that is, ecosystems without migration. In this study, we tested whether partial migration of certain species within the overall prey community affects foraging ecology of top predators and thereby alters energy pathways in food webs. We carried out the study in independent replicated freshwater lake systems, four with and four without opportunity for prey migration. Specifically, we compared predator foraging mode in lakes where cyprinid prey fish perform seasonal partial migrations into connected streams with lakes lacking migratory opportunities for prey fish. We found clear seasonal bottom-up effects of prey migration on predators, including changes in size structure and total biomass of ingested prey, size-specific changes in littoral versus pelagic origin of diet, and a higher degree of feast-and-famine for predators in systems with migratory prey. Our analyses further showed that partially migratory prey species constitute a larger part of the prey community in systems that allow migration. Hence, prey migrations have important implications for predator foraging ecology and may cause seasonal shifts in the importance of their supporting energy pathways. We suggest that such bottom-up effects of partial migration may be a widespread phenomenon both in aquatic and in terrestrial ecosystems

Biomanipulating streams : a supplementary tool in lake restoration

Removal of cyprinid fish is a widely used biomanipulation tool to transform turbid shallow eutrophic lakes in north temperate regions into a clear water state. We here evaluate the removal of cyprinids from streams as a supplement to lake fishing. Since cyprinids often aggregate in high densities in lake inlet/outlet streams during winter migration, removal of fish in this space-confined habitat may be cost-efficient as compared to fish removal in the lake habitat. In two consecutive years, we annually removed up to 35% of the dominant cyprinids from an inlet stream to a lake and argue that this could easily be increased with a more targeted fishing effort. Concurrently, we monitored species- and length-specific variation in migration propensity, to explore how this relates to efficient fish removal. Smaller planktivores generally had a much higher migratory propensity than larger benthivores. Hence, stream fishing specifically targets species and size groups that are less efficiently controlled with traditional lake fishing methods. As a rule of thumb, stream fishing is most efficient when water temperature is 2–6°C. Prior to implementing fish removals from streams, the potential evolutionary consequences of the targeted removal of migratory phenotypes should be considered

A field evaluation of long-term effects of PIT tagging

Passive integrated transponder (PIT)-tagging is commonly used in behavioural studies of fish, although long-term evaluations of effects from tagging under natural conditions are scarce. We PIT-tagged common bream Abramis brama, European perch Perca fluviatilis, pike Esox lucius and roach Rutilus rutilus, released them in their lakes of origin and recaptured them after 103–3269 days. Overall, tagged fish did not differ in condition from non-tagged fish, except for small R. rutilus that had a lower length-specific body mass in one lake in 1 year. We conclude that PIT-tagging in general has negligible long-term effects on fish condition