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1.
  • 2021
  • swepub:Mat__t
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2.
  • Glasbey, JC, et al. (author)
  • 2021
  • swepub:Mat__t
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3.
  • Tabiri, S, et al. (author)
  • 2021
  • swepub:Mat__t
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4.
  • Bravo, L, et al. (author)
  • 2021
  • swepub:Mat__t
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5.
  • 2021
  • swepub:Mat__t
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7.
  • Khatri, C, et al. (author)
  • Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
  • 2021
  • In: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
  • Journal article (peer-reviewed)abstract
    • Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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8.
  • Bousquet, Jean, et al. (author)
  • Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018) : Change management in allergic rhinitis and asthma multimorbidity using mobile technology
  • 2019
  • In: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 143:3, s. 864-879
  • Journal article (peer-reviewed)abstract
    • Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.
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9.
  • Menditto, Enrica, et al. (author)
  • Adherence to treatment in allergic rhinitis using mobile technology : The MASK Study
  • 2019
  • In: Clinical and Experimental Allergy. - : WILEY. - 0954-7894 .- 1365-2222. ; 49:4, s. 442-460
  • Journal article (peer-reviewed)abstract
    • Background: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. Objectives: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. Methods: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. Results: A total of 12143 users were registered. A total of 6949 users reported at least one VAS data recording. Among them, 1887 users reported >= 7 VAS data. About 1195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR >= 70% and PDC <= 1.25), 51 (4.23%) were partly adherent (MPR >= 70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR <70%). Of those, the largest group was non-adherent to medications and the time interval was increased in 442 (36.68%) users. Conclusion and clinical relevance: Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.
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11.
  • Fomalont, E. B., et al. (author)
  • THE 2014 ALMA LONG BASELINE CAMPAIGN: AN OVERVIEW
  • 2015
  • In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 808:1
  • Journal article (peer-reviewed)abstract
    • A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to make accurate images with resolutions of tens of milliarcseconds, which at submillimeter (submm) wavelengths requires baselines up to similar to 15 km. To develop and test this capability, a Long Baseline Campaign (LBC) was carried out from 2014 September to late November, culminating in end-to-end observations, calibrations, and imaging of selected Science Verification (SV) targets. This paper presents an overview of the campaign and its main results, including an investigation of the short-term coherence properties and systematic phase errors over the long baselines at the ALMA site, a summary of the SV targets and observations, and recommendations for science observing strategies at long baselines. Deep ALMA images of the quasar 3C 138 at 97 and 241 GHz are also compared to VLA 43 GHz results, demonstrating an agreement at a level of a few percent. As a result of the extensive program of LBC testing, the highly successful SV imaging at long baselines achieved angular resolutions as fine as 19 mas at similar to 350 GHz. Observing with ALMA on baselines of up to 15 km is now possible, and opens up new parameter space for submm astronomy.
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12.
  • Hudson, Lawrence N, et al. (author)
  • The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
  • 2017
  • In: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
  • Journal article (peer-reviewed)abstract
    • The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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14.
  • Hillier, Ladeana W, et al. (author)
  • Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
  • 2004
  • In: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716
  • Journal article (peer-reviewed)abstract
    • We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.
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15.
  • Lerner, M.S., et al. (author)
  • A 100 GHZ map of 3C 446
  • 1993
  • In: Astronomy and Astrophysics. - Les Ulis : EDP Sciences. - 0004-6361 .- 1432-0746. ; 280:1, s. 117-120
  • Journal article (peer-reviewed)abstract
    • The first map made from 100 GHz VLBI observations of the quasar/BL Lac object 3C446 is presented. This map represents a 25-fold increase in resolution compared to earlier maps. Our main conclusions are that the core of 3C 446 is still almost unresolved (less than or similar to 30 muas) at this frequency and that a jet extends several hundred microarcseconds at position angle almost-equal-to -142-degrees. A comparison is also made with observations at other size scales.
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16.
  • Rantakyrö, F.T., et al. (author)
  • 50 μas resolution VLBI images of AGN’s at λ3 mm
  • 1998
  • In: Astronomy and Astrophysics. - Berlin : Springer-Verlag. - 0004-6361 .- 1432-0746. ; 131, s. 451-467
  • Journal article (peer-reviewed)abstract
    • We present 15 images from the global mm-VLBI sessions in 1990 April at 100 GHz and 1993 April at 86 GHz. These observations probe the central engines of the 16 observed AGN's with up to 50 mu as resolution. Among other sources previously observed with lambda 3 mm VLBI we present the first lambda 3 mm maps of 0735+178, 0748+126, 1055+018, 2145+067, and CTA102, in total we have been able to image 13 out of the 16 observed sources. 6 out of the 13 imaged sources observed exhibit curvature and rapid structural changes, although the low dynamic range in two thirds of the maps limits the detection of weak features. Most of the sources have unresolved cores even at this high resolution. There is substantial evidence that the observed sources can be grouped into two general groups: A misaligned population with parsec scale jets in the form of low pitch helices and an aligned population with straight jets with small changes in PA due to intrinsic bends.
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17.
  • Bååth, L.B. 1948-, et al. (author)
  • The microarcsecond structure of 3C 273 at 3 MM
  • 1991
  • In: Astronomy and Astrophysics. - Les Ulis : EDP Sciences. - 0004-6361 .- 1432-0746. ; 241:1, s. L1-L4
  • Journal article (peer-reviewed)abstract
    • Recent improvements in data analysis and receiver techniques have allowed us to produce a map of the 100GHz emission from the compact radio source 3C273 with the unsurpassed resolution of 50-mu-as (microarcseconds). Our map shows that the structure within 300-mu-as (approximately 1.5.10(18).h-1 cm) has a position angle significantly different from the position angle of the jet observed at lower frequencies. There are also indications in our map that the inner structure has a more pronounced wiggling structure than has been observed on larger scales. The observations were made about 60 days from the start of the outburst of 1988. Most of the flux from the outburst is concentrated in a component which is elongated approximately (56 x 5).10(16).h-1 cm perpendicular to the overall jet-axis. The distance between this component and the core is approximately 128-mu-as, which corresponds to the distance expected from an apparent velocity of approximately 800-mu-as year-1.
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18.
  • Bååth, L.B. 1948-, et al. (author)
  • VLBI observations of active galactic nuclei at 3 MM
  • 1992
  • In: Astronomy and Astrophysics. - Les Ulis : EDP Sciences. - 0004-6361 .- 1432-0746. ; 257:1, s. 31-46
  • Journal article (peer-reviewed)abstract
    • Recent improvements in data analysis and receiver techniques have allowed us to produce maps of the 100 GHz emission from the compact cores of active galactic nuclei with the unsurpassed resolution of 50-mu-as (microarcseconds). We present here hybrid maps of a set of compact radio sources observed at two epochs with a global VLBI array. The high resolution enables us to show details of active galactic nuclei on size scales of 10(16)-10(17) cm. Jets are shown to be more curved in these inner parts than further out in the areas mapped with VLBI at lower frequencies. Our maps of the quasar 3C345 show that the curvature seen with lower resolution instruments continues very close to the core. New components are seen separating from the cores of 3C84 and BL Lac. We observe a component in 3C84 separating from the core with an apparent speed approximately 21000 km sec-1. The radio source OJ287 is still unresolved with our array, having a core size of less-than-or-similar-to 10(17) cm. There is no indication of any compact component in 3C279 which would be associated with the outburst in integrated flux density which happened some months before our observation. The flux density of the most compact component we observe in 3C279 agrees well with that of the quiet core as extrapolated from its radio spectrum at lower frequencies. The inner part of the radio jet of the giant elliptical galaxy M87 also shows a continuation of the structure on a larger size scale, with a structure we interpret as parts of a helical pattern. No fringes were found for 4C39.25 or Sgr A.
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19.
  • Emerson, Joanne B., et al. (author)
  • Host-linked soil viral ecology along a permafrost thaw gradient
  • 2018
  • In: Nature Microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 3:8, s. 870-880
  • Journal article (peer-reviewed)abstract
    • Climate change threatens to release abundant carbon that is sequestered at high latitudes, but the constraints on microbial metabolisms that mediate the release of methane and carbon dioxide are poorly understood(1-7). The role of viruses, which are known to affect microbial dynamics, metabolism and biogeochemistry in the oceans(8-10), remains largely unexplored in soil. Here, we aimed to investigate how viruses influence microbial ecology and carbon metabolism in peatland soils along a permafrost thaw gradient in Sweden. We recovered 1,907 viral populations (genomes and large genome fragments) from 197 bulk soil and size-fractionated metagenomes, 58% of which were detected in metatranscriptomes and presumed to be active. In silico predictions linked 35% of the viruses to microbial host populations, highlighting likely viral predators of key carbon-cycling microorganisms, including methanogens and methanotrophs. Lineage-specific virus/host ratios varied, suggesting that viral infection dynamics may differentially impact microbial responses to a changing climate. Virus-encoded glycoside hydrolases, including an endomannanase with confirmed functional activity, indicated that viruses influence complex carbon degradation and that viral abundances were significant predictors of methane dynamics. These findings suggest that viruses may impact ecosystem function in climate-critical, terrestrial habitats and identify multiple potential viral contributions to soil carbon cycling.
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20.
  • Gallardo, P. A., et al. (author)
  • Optical design concept of the CMB-S4 large-Aperture telescopes and cameras
  • 2022
  • In: Proceedings of SPIE, the International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 12190
  • Journal article (peer-reviewed)abstract
    • CMB-S4-the next-generation ground-based cosmic microwave background (CMB) experiment-will significantly advance the sensitivity of CMB measurements and improve our understanding of the origin and evolution of the universe. CMB-S4 will deploy large-Aperture telescopes fielding hundreds of thousands of detectors at millimeter wavelengths. We present the baseline optical design concept of the large-Aperture CMB-S4 telescopes, which consists of two optical configurations: (i) a new off-Axis, three-mirror, free-form anastigmatic design and (ii) the existing coma-corrected crossed-Dragone design. We also present an overview of the optical configuration of the array of silicon optics cameras that will populate the focal plane with 85 diffraction-limited optics tubes covering up to 9 degrees of field of view, up to 1.1 mm in wavelength. We describe the computational optimization methods that were put in place to implement the families of designs described here and give a brief update on the current status of the design effort. 
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22.
  • Miotto, P, et al. (author)
  • A standardised method for interpreting the association between mutations and phenotypic drug resistance in Mycobacterium tuberculosis
  • 2017
  • In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 50:6
  • Journal article (peer-reviewed)abstract
    • A clear understanding of the genetic basis of antibiotic resistance inMycobacterium tuberculosisis required to accelerate the development of rapid drug susceptibility testing methods based on genetic sequence.Raw genotype–phenotype correlation data were extracted as part of a comprehensive systematic review to develop a standardised analytical approach for interpreting resistance associated mutations for rifampicin, isoniazid, ofloxacin/levofloxacin, moxifloxacin, amikacin, kanamycin, capreomycin, streptomycin, ethionamide/prothionamide and pyrazinamide. Mutation frequencies in resistant and susceptible isolates were calculated, together with novel statistical measures to classify mutations as high, moderate, minimal or indeterminate confidence for predicting resistance.We identified 286 confidence-graded mutations associated with resistance. Compared to phenotypic methods, sensitivity (95% CI) for rifampicin was 90.3% (89.6–90.9%), while for isoniazid it was 78.2% (77.4–79.0%) and their specificities were 96.3% (95.7–96.8%) and 94.4% (93.1–95.5%), respectively. For second-line drugs, sensitivity varied from 67.4% (64.1–70.6%) for capreomycin to 88.2% (85.1–90.9%) for moxifloxacin, with specificity ranging from 90.0% (87.1–92.5%) for moxifloxacin to 99.5% (99.0–99.8%) for amikacin.This study provides a standardised and comprehensive approach for the interpretation of mutations as predictors ofM. tuberculosisdrug-resistant phenotypes. These data have implications for the clinical interpretation of molecular diagnostics and next-generation sequencing as well as efficient individualised therapy for patients with drug-resistant tuberculosis.
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23.
  • Wilson, R. M., et al. (author)
  • Functional capacities of microbial communities to carry out large scale geochemical processes are maintained during ex situ anaerobic incubation
  • 2021
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:2
  • Journal article (peer-reviewed)abstract
    • Mechanisms controlling CO2 and CH4 production in wetlands are central to understanding carbon cycling and greenhouse gas exchange. However, the volatility of these respiration products complicates quantifying their rates of production in the field. Attempts to circumvent the challenges through closed system incubations, from which gases cannot escape, have been used to investigate bulk in situ geochemistry. Efforts towards mapping mechanistic linkages between geochemistry and microbiology have raised concern regarding sampling and incubation-induced perturbations. Microorganisms are impacted by oxygen exposure, increased temperatures and accumulation of metabolic products during handling, storage, and incubation. We probed the extent of these perturbations, and their influence on incubation results, using high-resolution geochemical and microbial gene-based community profiling of anaerobically incubated material from three wetland habitats across a permafrost peatland. We compared the original field samples to the material anaerobically incubated over 50 days. Bulk geochemistry and phylum-level microbiota in incubations largely reflected field observations, but divergence between field and incubations occurred in both geochemistry and lineage-level microbial composition when examined at closer resolution. Despite the changes in representative lineages over time, inferred metabolic function with regards to carbon cycling largely reproduced field results suggesting functional consistency. Habitat differences among the source materials remained the largest driver of variation in geochemical and microbial differences among the samples in both incubations and field results. While incubations may have limited usefulness for identifying specific mechanisms, they remain a viable tool for probing bulk-scale questions related to anaerobic C cycling, including CO2 and CH4 dynamics
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24.
  • Murray, Alison E., et al. (author)
  • Roadmap for naming uncultivated Archaea and Bacteria
  • 2020
  • In: Nature Microbiology. - : NATURE PUBLISHING GROUP. - 2058-5276. ; 5:8, s. 987-994
  • Journal article (peer-reviewed)abstract
    • The assembly of single-amplified genomes (SAGs) and metagenome-assembled genomes (MAGs) has led to a surge in genome-based discoveries of members affiliated with Archaea and Bacteria, bringing with it a need to develop guidelines for nomenclature of uncultivated microorganisms. The International Code of Nomenclature of Prokaryotes (ICNP) only recognizes cultures as 'type material', thereby preventing the naming of uncultivated organisms. In this Consensus Statement, we propose two potential paths to solve this nomenclatural conundrum. One option is the adoption of previously proposed modifications to the ICNP to recognize DNA sequences as acceptable type material; the other option creates a nomenclatural code for uncultivated Archaea and Bacteria that could eventually be merged with the ICNP in the future. Regardless of the path taken, we believe that action is needed now within the scientific community to develop consistent rules for nomenclature of uncultivated taxa in order to provide clarity and stability, and to effectively communicate microbial diversity. In this Consensus Statement, the authors discuss the issue of naming uncultivated prokaryotic microorganisms, which currently do not have a formal nomenclature system due to a lack of type material or cultured representatives, and propose two recommendations including the recognition of DNA sequences as type material.
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25.
  • Woodcroft, Ben J., et al. (author)
  • Genome-centric view of carbon processing in thawing permafrost
  • 2018
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 560:7716, s. 49-
  • Journal article (peer-reviewed)abstract
    • As global temperatures rise, large amounts of carbon sequestered in permafrost are becoming available for microbial degradation. Accurate prediction of carbon gas emissions from thawing permafrost is limited by our understanding of these microbial communities. Here we use metagenomic sequencing of 214 samples from a permafrost thaw gradient to recover 1,529 metagenome-assembled genomes, including many from phyla with poor genomic representation. These genomes reflect the diversity of this complex ecosystem, with genus-level representatives for more than sixty per cent of the community. Meta-omic analysis revealed key populations involved in the degradation of organic matter, including bacteria whose genomes encode a previously undescribed fungal pathway for xylose degradation. Microbial and geochemical data highlight lineages that correlate with the production of greenhouse gases and indicate novel syntrophic relationships. Our findings link changing biogeochemistry to specific microbial lineages involved in carbon processing, and provide key information for predicting the effects of climate change on permafrost systems.
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26.
  • Emerson, Joanne B., et al. (author)
  • Diverse sediment microbiota shape methane emission temperature sensitivity in Arctic lakes
  • 2021
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12
  • Journal article (peer-reviewed)abstract
    • Northern post-glacial lakes are significant, increasing sources of atmospheric carbon through ebullition (bubbling) of microbially-produced methane (CH4) from sediments. Ebullitive CH4 flux correlates strongly with temperature, reflecting that solar radiation drives emissions. However, here we show that the slope of the temperature-CH4 flux relationship differs spatially across two post-glacial lakes in Sweden. We compared these CH4 emission patterns with sediment microbial (metagenomic and amplicon), isotopic, and geochemical data. The temperature-associated increase in CH4 emissions was greater in lake middles—where methanogens were more abundant—than edges, and sediment communities were distinct between edges and middles. Microbial abundances, including those of CH4-cycling microorganisms and syntrophs, were predictive of porewater CH4 concentrations. Results suggest that deeper lake regions, which currently emit less CH4 than shallower edges, could add substantially to CH4 emissions in a warmer Arctic and that CH4 emission predictions may be improved by accounting for spatial variations in sediment microbiota.
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27.
  • Gallardo, Patricio A., et al. (author)
  • Freeform three-mirror anastigmatic large-aperture telescope and receiver optics for CMB-S4
  • 2024
  • In: Applied Optics. - 1559-128X .- 2155-3165. ; 63:2, s. 310-321
  • Journal article (peer-reviewed)abstract
    • CMB-S4, the next-generation ground-based cosmic microwave background (CMB) observatory, will provide detailed maps of the CMB at millimeter wavelengths to dramatically advance our understanding of the origin and evolution of the universe. CMB-S4 will deploy large- and small-aperture telescopes with hundreds of thousands of detectors to observe the CMB at arcminute and degree resolutions at millimeter wavelengths. Inflationary science benefits from a deep delensing survey at arcminute resolutions capable of observing a large field of view at millimeter wavelengths. This kind of survey acts as a complement to a degree angular resolution survey. The delensing survey requires a nearly uniform distribution of cameras per frequency band across the focal plane. We present a large-throughput (9.4° field of view), large-aperture (5-m diameter) freeform three-mirror anastigmatic telescope and an array of 85 cameras for CMB observations at arcminute resolutions, which meets the needs of the delensing survey of CMB-S4. A detailed prescription of this three-mirror telescope and cameras is provided, with a series of numerical calculations that indicates expected optical performance and mechanical tolerance.
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29.
  • Bartho, Lucy A, et al. (author)
  • Circulating Chemerin Is Elevated in Women With Preeclampsia.
  • 2023
  • In: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 164:5
  • Journal article (peer-reviewed)abstract
    • Preeclampsia is a severe complication of pregnancy. Chemerin is an adipokine secreted from adipose tissue and highly expressed in placenta. This study evaluated the biomarker potential of circulating chemerin to predict preeclampsia.Maternal plasma and placenta were collected from women with early-onset preeclampsia (<34 weeks), with preeclampsia and eclampsia, or before preeclampsia diagnosis (36 weeks). Human trophoblast stem cells were differentiated into syncytiotrophoblast or extravillous trophoblasts across 96hours. Cells were cultured in 1% O2 (hypoxia) or 5% O2 (normoxia). Chemerin was measured by enzyme-linked immunosorbent assay (ELISA) and RARRES2 (gene coding chemerin) by reverse transcription-quantitative polymerase chain reaction.Circulating chemerin was increased in 46 women with early-onset preeclampsia (<34 weeks) compared to 17 controls (P < .0006). Chemerin was increased in placenta from 43 women with early-onset preeclampsia compared to 24 controls (P < .0001). RARRES2 was reduced in placenta from 43 women with early-onset preeclampsia vs 24 controls (P < .0001). Chemerin was increased in plasma from 26 women with established preeclampsia (P = .006), vs 15 controls. Circulating chemerin was increased in 23 women who later developed preeclampsia vs 182 who did not (P = 3.23 × 10-6). RARRES2 was reduced in syncytiotrophoblast (P = .005) or extravillous trophoblasts (P < .0001). Hypoxia increased RARRES2 expression in syncytiotrophoblast (P = .01) but not cytotrophoblast cells.Circulating chemerin was elevated in women with early-onset preeclampsia, established preeclampsia, and preceding preeclampsia diagnosis of preeclampsia. RARRES2 was dysregulated in placenta complicated by preeclampsia and may be regulated through hypoxia. Chemerin may have potential as a biomarker for preeclampsia but would need to be combined with other biomarkers.
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30.
  • Cruickshank, Tess, et al. (author)
  • Circulating growth differentiation factor 15 is increased preceding preeclampsia diagnosis: Implications as a disease biomarker
  • 2021
  • In: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 10:16
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: We investigated the biomarker potential of growth differentiation factor 15 (GDF-15), a stress response protein highly expressed in placenta, to predict preeclampsia. METHODS AND RESULTS: In 2 prospective cohorts (cohort 1: 960 controls, 39 women who developed preeclampsia; cohort 2: 950 controls, 41 developed preeclampsia), plasma concentrations of GDF-15 at 36 weeks’ gestation were significantly increased among those who developed preeclampsia (P<0.001), area under the receiver operating characteristic curves (AUC) of 0.66 and 0.71, respectively. In cohort 2 a ratio of sFlt-1/PlGF (a clinical biomarker for preeclampsia) had a sensitivity of 61.0% at 83.2% specificity to predict those who will develop preeclampsia (AUC of 0.79). A ratio of GDF-15×sFlt-1/PlGF yielded a sensitivity of 68.3% at 83.2% specificity (AUC of 0.82). GDF-15 was consistently elevated across a number of international cohorts: levels were higher in placenta and blood from women delivering <34 weeks’ gestation due to preterm preeclampsia in Melbourne, Australia; and in the blood at 26 to 32 weeks’ gestation among 57 women attending the Manchester Antenatal Vascular Service (MAViS, UK) who developed preeclampsia (P=0.0002), compared with 176 controls. In the Preeclampsia Obstetric adVerse Events biobank (PROVE, South Africa), plasma GDF-15 was significantly increased in women with preec-lampsia with severe features (P=0.02; n=14) compared to controls (n=14). CONCLUSIONS: We conclude circulating GDF-15 is elevated among women more likely to develop preeclampsia or diagnosed with the condition. It may have value as a clinical biomarker, including the potential to improve the sensitivity of sFlt-1/PlGF ratio.
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31.
  • de Mello, Lucas R., et al. (author)
  • Amyloid-like Self-Assembly of a Hydrophobic Cell-Penetrating Peptide and Its Use as a Carrier for Nucleic Acids
  • 2021
  • In: ACS Applied Bio Materials. - : American Chemical Society (ACS). - 2576-6422. ; 4:8, s. 6404-6416
  • Journal article (peer-reviewed)abstract
    • Cell-penetrating peptides (CPPs) are a topical subject potentially exploitable for creating nanotherapeutics for the delivery of bioactive loads. These compounds are often classified into three major categories according to their physicochemical characteristics: cationic, amphiphilic, and hydrophobic. Among them, the group of hydrophobic CPPs has received increasing attention in recent years due to toxicity concerns posed by highly cationic CPPs. The hexapeptide PFVYLI (P, proline; F, phenylalanine; V, valine; Y, tyrosine; L, leucine; and I, isoleucine), a fragment derived from the C-terminal portion of alpha 1-antitrypsin, is a prototypal example of hydrophobic CPP. This sequence shows reduced cytotoxicity and a capacity of nuclear localization, and its small size readily hints at its suitability as a building block to construct nanostructured materials. In this study, we examine the self-assembling properties of PFVYLI and investigate its ability to form noncovalent complexes with nucleic acids. By using a combination of biophysical tools including synchrotron small-angle X-ray scattering and atomic force microscopy-based infrared spectroscopy, we discovered that this CPP self-assembles into discrete nanofibrils with remarkable amyloidogenic features. Over the course of days, these fibrils coalesce into rodlike crystals that easily reach the micrometer range. Despite lacking cationic residues in the composition, PFVYLI forms noncovalent complexes with nucleic acids that retain beta-sheet pairing found in amyloid aggregates. In vitro vectorization experiments performed with doublestranded DNA fragments indicate that complexes promote the internalization of nucleic acids, revealing that tropism toward cell membranes is preserved upon complexation. On the other hand, transfection assays with splice-correction oligonucleotides (SCOs) for luciferase expression show limited bioactivity across a narrow concentration window, suggesting that the propensity to form amyloidogenic aggregates may trigger endosomal entrapment. We anticipate that the findings presented here open perspectives for using this archetypical hydrophobic CPP in the fabrication of nanostructured scaffolds, which potentially integrate properties of amyloids and translocation capabilities of CPPs.
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32.
  • Emerson, FJ, et al. (author)
  • The chromatin factors SET-26 and HCF-1 oppose the histone deacetylase HDA-1 in longevity and gene regulation in C. elegans
  • 2023
  • In: bioRxiv : the preprint server for biology. - : Cold Spring Harbor Laboratory.
  • Journal article (other academic/artistic)abstract
    • SET-26, HCF-1, and HDA-1 are highly conserved chromatin factors with key roles in development and aging. Here we present mechanistic insights into how these factors regulate gene expression and modulate longevity inC. elegans. We show that SET-26 and HCF-1 cooperate to regulate a common set of genes, and both antagonize the histone deacetylase HDA-1 to limit longevity. We propose a model in which SET-26 recruits HCF-1 to chromatin in somatic cells, where they stabilize each other at the promoters of a subset of genes, particularly mitochondrial function genes, and regulate their expression. HDA-1 opposes SET-26 and HCF-1 on the regulation of a subset of their common target genes and in longevity. Our findings suggest that SET-26, HCF-1, and HDA-1 comprise a mechanism to fine-tune gene expression and longevity and likely have important implications for the mechanistic understanding of how these factors function in diverse organisms, particularly in aging biology.
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33.
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34.
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35.
  • Kandel, Manju, et al. (author)
  • PSG7 and 9 (Pregnancy-Specific beta-1 Glycoproteins 7 and 9) : Novel Biomarkers for Preeclampsia
  • 2022
  • In: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 11:7
  • Journal article (peer-reviewed)abstract
    • Background: Preeclampsia is pregnancy specific, involving significant maternal endothelial dysfunction. Predictive biomarkers are lacking. We evaluated the biomarker potential, expression, and function of PSG7 (pregnancy-specific beta-1 glycoprotein 7) and PSG9 (pregnancy-specific beta-1 glycoprotein 9) in preeclampsia.Methods and Results: At 36 weeks gestation preceding term preeclampsia diagnosis, PSG7 and PSG9 (in Australian cohorts of n=918 and n=979, respectively) were significantly increased before the onset of term preeclampsia (PSG7, P=0.013; PSG9, P=0.0011). In samples collected at 28 to 32 weeks from those with preexisting cardiovascular disease and at high risk of preeclampsia (Manchester Antenatal Vascular Service, UK cohort, n=235), both PSG7 and PSG9 were also significantly increased preceding preeclampsia onset (PSG7, P<0.0001; PSG9, P=0.0003) relative to controls. These changes were validated in the plasma and placentas of patients with established preeclampsia who delivered at <34 weeks gestation (PSG7, P=0.0008; PSG9, P<0.0001). To examine whether PSG7 and PSG9 are associated with increasing disease severity, we measured them in a cohort from South Africa stratified for this outcome, the PROVE (Preeclampsia Obstetric Adverse Events) cohort (n=72). PSG7 (P=0.0027) and PSG9 (P=0.0028) were elevated among patients who were preeclamptic with severe features (PROVE cohort), but not significantly changed in those without severe features or with eclampsia. In syncytialized first trimester cytotrophoblast stem cells, exposure to TNF alpha (tumor necrosis factor alpha) or IL-6 (interleukin 6) significantly increased the expression and secretion of PSG7 and PSG9. In contrast, when we treated primary endothelial cells with recombinant PSG7 and PSG9, we only observed modest changes in Flt-1 (FMS-like tyrosine kinase-1) expression and Plgf (placental growth factor) expression, and no other effects on proangiogenic/antiangiogenic or endothelial dysfunction markers were observed.Conclusions: Circulating PSG7 and PSG9 are increased before preeclampsia onset and among those with established disease with their production and release potentially driven by placental inflammation.
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36.
  • Kandel, Manju, et al. (author)
  • PSG7 and 9 (Pregnancy-Specific β-1 Glycoproteins 7 and 9): Novel Biomarkers for Preeclampsia. : Pregnancy Specific beta-1 Glycoproteins (PSG) 7 and 9 - novel biomarkers for preeklampsia.
  • 2022
  • In: Journal of the American Heart Association. - 2047-9980. ; 11:7
  • Journal article (peer-reviewed)abstract
    • Background Preeclampsia is pregnancy specific, involving significant maternal endothelial dysfunction. Predictive biomarkers are lacking. We evaluated the biomarker potential, expression, and function of PSG7 (pregnancy-specific β-1 glycoprotein 7) and PSG9 (pregnancy-specific β-1 glycoprotein 9) in preeclampsia. Methods and Results At 36weeks gestation preceding term preeclampsia diagnosis, PSG7 and PSG9 (in Australian cohorts of n=918 and n=979, respectively) were significantly increased before the onset of term preeclampsia (PSG7, P=0.013; PSG9, P=0.0011). In samples collected at 28 to 32weeks from those with preexisting cardiovascular disease and at high risk of preeclampsia (Manchester Antenatal Vascular Service, UK cohort, n=235), both PSG7 and PSG9 were also significantly increased preceding preeclampsia onset (PSG7, P<0.0001; PSG9, P=0.0003) relative to controls. These changes were validated in the plasma and placentas of patients with established preeclampsia who delivered at <34weeks gestation (PSG7, P=0.0008; PSG9, P<0.0001). To examine whether PSG7 and PSG9 are associated with increasing disease severity, we measured them in a cohort from South Africa stratified for this outcome, the PROVE (Preeclampsia Obstetric Adverse Events) cohort (n=72). PSG7 (P=0.0027) and PSG9 (P=0.0028) were elevated among patients who were preeclamptic with severe features (PROVE cohort), but not significantly changed in those without severe features or with eclampsia. In syncytialized first trimester cytotrophoblast stem cells, exposure to TNFα (tumor necrosis factor α) or IL-6 (interleukin 6) significantly increased the expression and secretion of PSG7 and PSG9. In contrast, when we treated primary endothelial cells with recombinant PSG7 and PSG9, we only observed modest changes in Flt-1 (FMS-like tyrosine kinase-1) expression and Plgf (placental growth factor) expression, and no other effects on proangiogenic/antiangiogenic or endothelial dysfunction markers were observed. Conclusions Circulating PSG7 and PSG9 are increased before preeclampsia onset and among those with established disease with their production and release potentially driven by placental inflammation.
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37.
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38.
  • Mello, Lucilene D., et al. (author)
  • Electrochemical and spectroscopic evidences of the interaction between DNA and Pt(II)(dppf)-complex
  • 2009
  • In: BioMetals. - : Springer Science and Business Media LLC. - 0966-0844 .- 1572-8773. ; 22:2, s. 385-392
  • Journal article (peer-reviewed)abstract
    • The interaction of Pt(II)(dppf)-complex, namely [Pt(dppf)(H2O)(2)](2+) with DNA was investigated by DPV and H-1-NMR techniques. The results showed that the interaction process has been characterized by changes in the electrochemical parameters of both compounds and the formation of a new anodic current peak close to the anodic current peak of the [Pt(dppf)(H2O)(2)](2+). In addition, the H-1-NMR spectra show that the coordination of Pt(II)(dppf)-complex to dsDNA occurs via N(7) of guanine. Others parameters like pH and ionic strength that affect the interaction process were also investigated.
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39.
  • Rice, L J, et al. (author)
  • Concurrence of the strengths and difficulties questionnaire and developmental behaviour checklist among children with an intellectual disability.
  • 2018
  • In: Journal of Intellectual Disability Research. - : Wiley. - 0964-2633 .- 1365-2788. ; 62:2, s. 150-155
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The Strengths and Difficulties Questionnaire (SDQ) is widely used to measure emotional and behavioural problems in typically developing young people, although there is some evidence that it may also be suitable for children with intellectual disability (ID). The Developmental Behaviour Checklist - Parent version (DBC-P) is a measure of emotional and behavioural problems that was specifically designed for children and adolescents with an ID. The DBC-P cut-off has high agreement with clinical diagnosis. The aim of this study was to estimate the relationship between DBC-P and SDQ scores in a sample of children with ID.METHOD: Parents of 83 young people with ID aged 4-17 years completed the parent versions of the SDQ and the DBC-P. We evaluated the concurrent validity of the SDQ and DBC-P total scores, and the agreement between the DBC-P cut-off and the SDQ cut-offs for 'borderline' and 'abnormal' behaviour.RESULTS: The SDQ total difficulties score correlated well with the DBC-P total behaviour problem score. Agreement between the SDQ borderline cut-off and the DBC-P cut-off for abnormality was high (83%), but was lower for the SDQ abnormal cut-off (75%). Positive agreement between the DBC-P and the SDQ borderline cut-off was also high, with the SDQ borderline cut-off identifying 86% of those who met the DBC-P criterion. Negative agreement was weaker, with the SDQ borderline cut-off identifying only 79% of the participants who did not meet the DBC-P cut-off.CONCLUSION: The SDQ borderline cut-off has some validity as a measure of overall levels of behavioural and emotional problems in young people with ID, and may be useful in epidemiological studies that include participants with and without ID. However, where it is important to focus on behavioural profiles in children with ID, a specialised ID instrument with established psychometric properties, such as the DBC-P, may provide more reliable and valid information.
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