32 research outputs found
Seasonal plankton dynamics in Kongsfjorden during two years of contrasting environmental conditions
Seasonal plankton time-series data are presented from Kongsfjorden from two years with contrasting environmental conditions. Kongsfjorden (west coast of Spitsbergen – 79°N) integrates inputs from Atlantic and Arctic waters, and glacier run-off, and is thus a prime location to study impacts on ecosystem dynamics of key environmental drivers that are relevant across the Arctic. Despite extensive research in Kongsfjorden, seasonally-resolved data are scarce. From late April/early May to early September 2019 and 2020, we conducted pelagic sampling at a mid-fjord station at mostly weekly to bi-weekly resolution investigating the environmental drivers of phyto- and zooplankton community composition and phenology. During spring 2019, Atlantic water masses with temperatures > 1 °C were found throughout the upper 250 m of the water column, and little sea ice occurred in the fjord. Spring 2020, in turn, was characterized by the presence of local water masses with sub-zero temperatures and relatively extensive sea-ice cover. The most striking contrast between the two years was the difference in phytoplankton spring bloom composition. In 2019, the spring bloom was dominated by the colonial stage of the haptophyte Phaeocystis pouchetii and diatoms played a minor role, while the spring bloom in 2020 was dominated by diatoms of the genus Thalassiosira succeeded by P. pouchetii. Selective grazing by large copepods and water mass structure seem to have been the decisive factors explaining the marked difference in diatom spring bloom biomass between the years while similar spring abundances of P. pouchetii in both years indicated that this species was less impacted by those factors. Our data suggest that differences in spring bloom composition impacted trophic transfer and carbon export. Recruitment of the dominant copepods Calanus finmarchicus and C. glacialis, Cirripedia and euphausiid larvae as well as the export of carbon to the seabed was more efficient during the diatom-dominated compared to the P. pouchetii–dominated spring bloom. In summer, the plankton composition shifted towards a flagellate-dominated community characterized by mixo- and heterotrophic taxa adapted to a lower nutrient regime and strong top-down control by copepod grazers. However, residual silicic acid after the P. pouchetii–dominated spring bloom fueled a late summer diatom bloom in 2019. Our data provide a first glimpse into the environmental drivers of plankton phenology and underline that high-resolution monitoring over many annual cycles is required to resolve the ephemeral variations of plankton populations against the backdrop of climate change.publishedVersio
Evolution of CRISPR-associated endonucleases as inferred from resurrected proteins
Clustered regularly interspaced short palindromic repeats (CRISPR)-associated Cas9 is an effector protein that targets invading DNA and plays a major role in the prokaryotic adaptive immune system. Although Streptococcus pyogenes CRISPR–Cas9 has been widely studied and repurposed for applications including genome editing, its origin and evolution are poorly understood. Here, we investigate the evolution of Cas9 from resurrected ancient nucleases (anCas) in extinct firmicutes species that last lived 2.6 billion years before the present. We demonstrate that these ancient forms were much more flexible in their guide RNA and protospacer-adjacent motif requirements compared with modern-day Cas9 enzymes. Furthermore, anCas portrays a gradual palaeoenzymatic adaptation from nickase to double-strand break activity, exhibits high levels of activity with both single-stranded DNA and single-stranded RNA targets and is capable of editing activity in human cells. Prediction and characterization of anCas with a resurrected protein approach uncovers an evolutionary trajectory leading to functionally flexible ancient enzymes.This work has been supported by grant nos. PID2019-109087RB-I00 (to R.P.-J.) and RTI2018-101223-B-I00 and PID2021-127644OB-I00 (to L.M.) from the Spanish Ministry of Science and Innovation. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 964764 (to R.P.-J.). The content presented in this document represents the views of the authors, and the European Commission has no liability in respect to the content. We acknowledge financial support from the Spanish Foundation for the Promotion of Research of Amyotrophic Lateral Sclerosis. A.F. acknowledges Spanish Center for Biomedical Network Research on Rare Diseases (CIBERE) intramural funds (no. ER19P5AC756/2021). F.J.M.M. acknowledges research support by Conselleria d’Educació, Investigació, Cultura i Esport from Generalitat Valenciana, research project nos. PROMETEO/2017/129 and PROMETEO/2021/057. M.M. acknowledges funding from CIBERER (grant no. ER19P5AC728/2021). The work has received funding from the Regional Government of Madrid (grant no. B2017/BMD3721 to M.A.M.-P.) and from Instituto de Salud Carlos III, cofounded with the European Regional Development Fund ‘A way to make Europe’ within the National Plans for Scientific and Technical Research and Innovation 2017–2020 and 2021–2024 (nos. PI17/1659, PI20/0429 and IMP/00009; to M.A.M.-P. B.P.K. was supported by an MGH ECOR Howard M. Goodman Award and NIH P01 HL142494
A simple approach to obtain hybrid Au-loaded polymeric nanoparticles with a tunable metal load
A new strategy to nanoengineer multi-functional polymer–metal hybrid nanostructures is reported. By
using this protocol the hurdles of most of the current developments concerning covalent and noncovalent
attachment of polymers to preformed inorganic nanoparticles (NPs) are overcome. The strategy
is based on the in situ reduction of metal precursors using the polymeric nanoparticle as a nanoreactor.
Gold nanoparticles and poly(DL-lactic-co-glycolic acid), PLGA, are located in the core and shell, respectively.
This novel technique enables the production of PLGA NPs smaller than 200 nm that bear either a
single encapsulated Au NP or several smaller NPs with tunable sizes and a 100% loading efficiency. In situ
reduction of Au ions inside the polymeric NPs was achieved on demand by using heat to activate the
reductive effect of citrate ions. In addition, we show that the loading of the resulting Au NPs inside the
PLGA NPs is highly dependent on the surfactant used. Electron microscopy, laser irradiation, UV-Vis and
fluorescence spectroscopy characterization techniques confirm the location of Au nanoparticles. These
promising results indicate that these hybrid nanomaterials could be used in theranostic applications or as
contrast agents in dark-field imaging and computed tomograph
Boosting background suppression in the NEXT experiment through Richardson-Lucy deconvolution
Next-generation neutrinoless double beta decay experiments aim for half-life sensitivities of similar to 10(27) yr, requiring suppressing backgrounds to < 1 count/tonne/yr. For this, any extra background rejection handle, beyond excellent energy resolution and the use of extremely radiopure materials, is of utmost importance. The NEXT experiment exploits differences in the spatial ionization patterns of double beta decay and single-electron events to discriminate signal from background. While the former display two Bragg peak dense ionization regions at the opposite ends of the track, the latter typically have only one such feature. Thus, comparing the energies at the track extremes provides an additional rejection tool. The unique combination of the topology-based background discrimination and excellent energy resolution (1% FWHM at the Q-value of the decay) is the distinguishing feature of NEXT. Previous studies demonstrated a topological background rejection factor of 5 when reconstructing electron-positron pairs in the Tl-208 1.6 MeV double escape peak (with Compton events as background), recorded in the NEXT-White demonstrator at the Laboratorio Subterraneo de Canfranc, with 72% signal efficiency. This was recently improved through the use of a deep convolutional neural network to yield a background rejection factor of similar to 10 with 65% signal efficiency. Here, we present a new reconstruction method, based on the Richardson-Lucy deconvolution algorithm, which allows reversing the blurring induced by electron diffusion and electroluminescence light production in the NEXT TPC. The new method yields highly refined 3D images of reconstructed events, and, as a result, significantly improves the topological background discrimination. When applied to real-data 1.6 MeV e(-)e(+) pairs, it leads to a background rejection factor of 27 at 57% signal efficiency.The NEXT Collaboration acknowledges support from the following agencies and institutions: the European Research Council (ERC) under the Advanced Grant 339787-NEXT; the European Union's Framework Programme for Research and Innovation Horizon 2020 (2014-2020) under the Grant Agreements No. 674896, 690575 and 740055; the Ministerio de Economia y Competitividad and the Ministerio de Ciencia, Innovacion y Universidades of Spain under grants FIS2014-53371-C04, RTI2018-095979, the Severo Ochoa Program grants SEV-2014-0398 and CEX2018-000867-S, and the Maria de Maeztu Program MDM-2016-0692; the Generalitat Valenciana under grants PROMETEO/2016/120 and SEJI/2017/011; the Portuguese FCT under project PTDC/FIS-NUC/2525/2014 and under projects UID/04559/2020 to fund the activities of LIBPhys-UC; the U.S. Department of Energy under contracts No. DE-AC02-06CH11357 (Argonne National Laboratory), DE-AC02-07CH11359 (Fermi National Accelerator Laboratory), DE-FG02-13ER42020 (Texas A&M) and DE-SC0019223/DE-SC0019054 (University of Texas at Arlington); the University of Texas at Arlington (U.S.A.); and the Pazy Foundation (Israel) under grants 877040 and 877041. DGD acknowledges Ramon y Cajal program (Spain) under contract number RYC-2015-18820. JM-A acknowledges support from Fundacion Bancaria "la Caixa" (ID 100010434), grant code LCF/BQ/PI19/11690012. AS acknowledges support from the Kreitman School of Advanced Graduate Studies at Ben-Gurion University.
Documen
Mortality prediction in chronic obstructive pulmonary disease comparing the GOLD 2015 and GOLD 2019 staging: a pooled analysis of individual patient data
In 2019, The Global Initiative for Chronic Obstructive Lung Disease (GOLD) modified the grading system for patients with COPD, creating 16 subgroups (1A–4D). As part of the COPD Cohorts Collaborative International Assessment (3CIA) initiative, we aim to compare the mortality prediction of the 2015 and 2019 COPD GOLD staging systems.
We studied 17 139 COPD patients from the 3CIA study, selecting those with complete data. Patients were classified by the 2015 and 2019 GOLD ABCD systems, and we compared the predictive ability for 5-year mortality of both classifications.
In total, 17 139 patients with COPD were enrolled in 22 cohorts from 11 countries between 2003 and 2017; 8823 of them had complete data and were analysed. Mean±sd age was 63.9±9.8 years and 62.9% were male. GOLD 2019 classified the patients in milder degrees of COPD. For both classifications, group D had higher mortality. 5-year mortality did not differ between groups B and C in GOLD 2015; in GOLD 2019, mortality was greater for group B than C. Patients classified as group A and B had better sensitivity and positive predictive value with the GOLD 2019 classification than GOLD 2015. GOLD 2015 had better sensitivity for group C and D than GOLD 2019. The area under the curve values for 5-year mortality were only 0.67 (95% CI 0.66–0.68) for GOLD 2015 and 0.65 (95% CI 0.63–0.66) for GOLD 2019
Large-scale external validation and comparison of prognostic models: an application to chronic obstructive pulmonary disease
Background: External validations and comparisons of prognostic models or scores are a prerequisite for their use in routine clinical care but are lacking in most medical fields including chronic obstructive pulmonary disease (COPD). Our aim was to externally validate and concurrently compare prognostic scores for 3-year all-cause mortality in mostly multimorbid patients with COPD. Methods: We relied on 24 cohort studies of the COPD Cohorts Collaborative International Assessment consortium, corresponding to primary, secondary, and tertiary care in Europe, the Americas, and Japan. These studies include globally 15,762 patients with COPD (1871 deaths and 42,203 person years of follow-up). We used network meta-analysis adapted to multiple score comparison (MSC), following a frequentist two-stage approach; thus, we were able to compare all scores in a single analytical framework accounting for correlations among scores within cohorts. We assessed transitivity, heterogeneity, and inconsistency and provided a performance ranking of the prognostic scores. Results: Depending on data availability, between two and nine prognostic scores could be calculated for each cohort. The BODE score (body mass index, airflow obstruction, dyspnea, and exercise capacity) had a median area under the curve (AUC) of 0.679 [1st quartile-3rd quartile = 0.655-0.733] across cohorts. The ADO score (age, dyspnea, and airflow obstruction) showed the best performance for predicting mortality (difference AUC(ADO) - AUC(BODE) = 0.015 [95% confidence interval (CI) = - 0.002 to 0.032]; p = 0.08) followed by the updated BODE (AUCBODE updated - AUCBODE = 0.008 [95% CI = -0.005 to +0.022]; p = 0.23). The assumption of transitivity was not violated. Heterogeneity across direct comparisons was small, and we did not identify any local or global inconsistency. Conclusions: Our analyses showed best discriminatory performance for the ADO and updated BODE scores in patients with COPD. A limitation to be addressed in future studies is the extension of MSC network meta-analysis to measures of calibration. MSC network meta-analysis can be applied to prognostic scores in any medical field to identify the best scores, possibly paving the way for stratified medicine, public health, and research
The Spanish NE Arctic Cod Fishery in 2018
EVAPESLE4Evaluación de los Stocks Explotados por las PesquerÃas Lejanas Españolas en el Atlántico Norte
The Spanish NE Arctic Cod Fishery in 2017
EVAPESLE4Evaluación de los Stocks Explotados por las PesquerÃas Lejanas Españolas en el Atlántico Norte