A re‐evaluation of the Plenus Cold Event, and the links between CO2, temperature, and seawater chemistry during OAE 2

International audienceThe greenhouse world of the mid‐Cretaceous (~94 Ma) was punctuated by an episode of abrupt climatic upheaval: Oceanic Anoxic Event 2 (OAE 2). High‐resolution climate records reveal considerable changes in temperature, carbon cycling, and ocean chemistry during this climatic perturbation. In particular, an interval of cooling has been detected in the English Chalk on the basis of an invasive boreal fauna and bulk oxygen‐isotope excursions registered during the early stages of OAE 2—a phenomenon known as the Plenus Cold Event (PCE), which has tentatively been correlated with climatic shifts worldwide.Here we present new high‐resolution neodymium‐, carbon‐, and oxygen‐isotope data, as well as elemental chromium concentrations and cerium anomalies, from the English Chalk exposed at Dover, UK, which we evaluate in the context of >400 records from across the globe. A negative carbon‐isotope excursion that correlates with the original ‘PCE’ is consistently expressed worldwide, and CO2 proxy records, where available, indicate a rise and subsequent fall in CO2 over the Plenus interval. However, variability in the timing and expression of cooling at different sites suggests that, although sea‐surface paleo‐temperatures may reflect a response to global CO2 change, local processes likely played a dominant role at many sites. Variability in the timing and expression of changes in water‐mass character, and problems in determining the driver of observed proxy changes, suggest that no single simple mechanism can link the carbon cycle to oceanography during the Plenus interval and other factors including upwelling and circulation patterns were locally important. As such, it is proposed that the Plenus carbon‐isotope event is a more reliable stratigraphic marker to identify the Plenus interval, rather than any climatic shifts that may have been overprinted by local effects

Real-space observation of fluctuating antiferromagnetic domains

Magnetic domains play a fundamental role in physics of magnetism and its technological applications. Dynamics of antiferromagnetic domains is poorly understood, although antiferromagnets are expected to be extensively used in future electronic devices wherein it determines the stability and operational speed. Dynamics of antiferromagnets also features prominently in the studies of topological quantum matter. Real-space imaging of fluctuating antiferromagnetic domains is therefore highly desired but has never been demonstrated. We use coherent x-ray diffraction to obtain videos of fluctuating micrometer-scale antiferromagnetic domains in Ni2MnTeO6 on time scales from 10-1 to 103 s. In the collinear phase, thermally activated domain wall motion is observed in the vicinity of the Néel temperature. Unexpectedly, the fluctuations persist through the full range of the higher-temperature helical phase. These observations illustrate the high potential significance of the dynamic domain imaging in phase transition studies and in magnetic device research

Design and Synthesis of Brain Penetrant Trypanocidal N-Myristoyltransferase Inhibitors

<i>N</i>-Myristoyltransferase (NMT) represents a promising drug target within the parasitic protozoa <i>Trypanosoma brucei</i> (<i>T. brucei</i>), the causative agent for human African trypanosomiasis (HAT) or sleeping sickness. We have previously validated <i>T. brucei</i> NMT as a promising druggable target for the treatment of HAT in both stages 1 and 2 of the disease. We report on the use of the previously reported DDD85646 (<b>1</b>) as a starting point for the design of a class of potent, brain penetrant inhibitors of <i>T. brucei</i> NMT

Alternative translation initiation augments the human mitochondrial proteome.

Alternative translation initiation (ATI) is a mechanism of producing multiple proteins from a single transcript, which in some cases regulates trafficking of proteins to different cellular compartments, including mitochondria. Application of a genome-wide computational screen predicts a cryptic mitochondrial targeting signal for 126 proteins in mouse and man that is revealed when an AUG codon located downstream from the canonical initiator methionine codon is used as a translation start site, which we term downstream ATI (dATI). Experimental evidence in support of dATI is provided by immunoblotting of endogenous truncated proteins enriched in mitochondrial cell fractions or of co-localization with mitochondria using immunocytochemistry. More detailed cellular localization studies establish mitochondrial targeting of a member of the cytosolic poly(A) binding protein family, PABPC5, and of the RNA/DNA helicase PIF1α. The mitochondrial isoform of PABPC5 co-immunoprecipitates with the mitochondrial poly(A) polymerase, and is markedly reduced in abundance when mitochondrial DNA and RNA are depleted, suggesting it plays a role in RNA metabolism in the organelle. Like PABPC5 and PIF1α, most of the candidates identified by the screen are not currently annotated as mitochondrial proteins, and so dATI expands the human mitochondrial proteome

Effectiveness of Denitrifying Bioreactors on Water Pollutant Reduction from Agricultural Areas

HighlightsDenitrifying woodchip bioreactors treat nitrate-N in a variety of applications and geographies.This review focuses on subsurface drainage bioreactors and bed-style designs (including in-ditch).Monitoring and reporting recommendations are provided to advance bioreactor science and engineering. Denitrifying bioreactors enhance the natural process of denitrification in a practical way to treat nitrate-nitrogen (N) in a variety of N-laden water matrices. The design and construction of bioreactors for treatment of subsurface drainage in the U.S. is guided by USDA-NRCS Conservation Practice Standard 605. This review consolidates the state of the science for denitrifying bioreactors using case studies from across the globe with an emphasis on full-size bioreactor nitrate-N removal and cost-effectiveness. The focus is on bed-style bioreactors (including in-ditch modifications), although there is mention of denitrifying walls, which broaden the applicability of bioreactor technology in some areas. Subsurface drainage denitrifying bioreactors have been assessed as removing 20% to 40% of annual nitrate-N loss in the Midwest, and an evaluation across the peer-reviewed literature published over the past three years showed that bioreactors around the world have been generally consistent with that (N load reduction median: 46%; mean ±SD: 40% ±26%; n = 15). Reported N removal rates were on the order of 5.1 g N m-3 d-1 (median; mean ±SD: 7.2 ±9.6 g N m-3 d-1; n = 27). Subsurface drainage bioreactor installation costs have ranged from less than $5,000 to$27,000, with estimated cost efficiencies ranging from less than $2.50 kg-1 N year-1 to roughly$20 kg-1 N year-1 (although they can be as high as $48 kg-1 N year-1). A suggested monitoring setup is described primarily for the context of conservation practitioners and watershed groups for assessing annual nitrate-N load removal performance of subsurface drainage denitrifying bioreactors. Recommended minimum reporting measures for assessing and comparing annual N removal performance include: bioreactor dimensions and installation date; fill media size, porosity, and type; nitrate-N concentrations and water temperatures; bioreactor flow treatment details; basic drainage system and bioreactor design characteristics; and N removal rate and efficiency

Trials and tribulations of recruiting 2,000 older women onto a clinical trial investigating falls and fractures : vital D study

Background Randomised, placebo-controlled trials are needed to provide evidence demonstrating safe, effective interventions that reduce falls and fractures in the elderly. The quality of a clinical trial is dependent on successful recruitment of the target participant group. This paper documents the successes and failures of recruiting over 2,000 women aged at least 70 years and at higher risk of falls or fractures onto a placebo-controlled trial of six years duration. The characteristics of study participants at baseline are also described for this study.Methods The Vital D Study recruited older women identified at high risk of fracture through the use of an eligibility algorithm, adapted from identified risk factors for hip fracture. Participants were randomised to orally receive either 500,000 IU vitamin D3 (cholecalciferol) or placebo every autumn for five consecutive years. A variety of recruitment strategies were employed to attract potential participants.Results Of the 2,317 participants randomised onto the study, 74% (n = 1716/2317) were consented onto the study in the last five months of recruiting. This was largely due to the success of a targeted mail-out. Prior to this only 541 women were consented in the 18 months of recruiting. A total of 70% of all participants were recruited as a result of targeted mail-out. The response rate from the letters increased from 2 to 7% following revision of the material by a public relations company. Participant demographic or risk factor profile did not differ between those recruited by targeted mail-outs compared with other methods.Conclusion The most successful recruitment strategy was the targeted mail-out and the response rate was no higher in the local region where the study had extensive exposure through other recruiting strategies. The strategies that were labour-intensive and did not result in successful recruitment include the activities directed towards the GP medical centres. Comprehensive recruitment programs employ overlapping strategies simultaneously with ongoing assessment of recruitment rates. In our experience, and others direct mail-outs work best although rights to privacy must be respected. <br /

Bending the curve of global freshwater biodiversity loss: an emergency recovery plan

Despite their limited spatial extent, freshwater ecosystems host remarkable biodiversity, including one-third of all vertebrate species. This biodiversity is declining dramatically: Globally, wetlands are vanishing three times faster than forests, and freshwater vertebrate populations have fallen more than twice as steeply as terrestrial or marine populations. Threats to freshwater biodiversity are well documented but coordinated action to reverse the decline is lacking. We present an Emergency Recovery Plan to bend the curve of freshwater biodiversity loss. Priority actions include accelerating implementation of environmental flows; improving water quality; protecting and restoring critical habitats; managing the exploitation of freshwater ecosystem resources, especially species and riverine aggregates; preventing and controlling nonnative species invasions; and safeguarding and restoring river connectivity. We recommend adjustments to targets and indicators for the Convention on Biological Diversity and the Sustainable Development Goals and roles for national and international state and nonstate actors

Longitudinal realist evaluation of the dementia PersonAlised care team (D-PACT) intervention: protocol

BACKGROUND: Different dementia support roles exist but evidence is lacking on which aspects are best, for whom and in what circumstance, and on their associated costs and benefits. Phase 1 of the Dementia PersonAlised Care Team programme (D-PACT), developed a post-diagnostic primary care-based intervention for people with dementia and their carers and assessed the feasibility of a trial. AIM: Phase 2 of the programme aims to 1) refine our programme theory on how, when and for whom the intervention works and 2) evaluate its value and impact. DESIGN & SETTING: A realist longitudinal mixed-methods evaluation will be conducted in urban, rural, and coastal areas across Southwest and Northwest England where low-income groups or ethnic minorities (eg, South Asian) are represented. Design was informed by patient, public and professional stakeholder input and Phase one findings. METHOD: High volume qualitative and quantitative data will be collected longitudinally from people with dementia, carers and practitioners. Analyses will comprise: 1) realist longitudinal case studies; 2) conversation analysis of recorded interactions; 3) statistical analyses of outcome and experience questionnaires; 4 a) health economic analysis examining costs of delivery; 4b) realist economic analysis of high-cost events and 'near misses'. All findings will be synthesised using a joint display table, evidence appraisal tool, triangulation and stakeholder co-analysis. CONCLUSION: Our realist evaluation will describe how, why and for whom the intervention leads (or not) to change over time; it also demonstrates how a non-randomised design can be more appropriate for complex interventions with similar questions or populations