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Showing papers by "Bielefeld University published in 2019"


Journal ArticleDOI
TL;DR: An overview of current super-resolution microscopy techniques is given and guidance on how best to use them to foster biological discovery is provided.
Abstract: Super-resolution microscopy (SRM) bypasses the diffraction limit, a physical barrier that restricts the optical resolution to roughly 250 nm and was previously thought to be impenetrable. SRM techniques allow the visualization of subcellular organization with unprecedented detail, but also confront biologists with the challenge of selecting the best-suited approach for their particular research question. Here, we provide guidance on how to use SRM techniques advantageously for investigating cellular structures and dynamics to promote new discoveries.

665 citations


Journal ArticleDOI
TL;DR: The main goal of the German Socio-Economic Panel (SOEP) is in line with the views and visions expressed in Angus Deaton's lecture as discussed by the authors, which serves a global research community by providing representative longitudinal data of private households.
Abstract: In his 2015 Economic Sciences Nobel lecture, Angus Deaton emphasized key issues for understanding welfare-enhancing policies (see Deaton 2015): First, differences in resources across individuals should be measured not only at specific points in time but also across the life course. Second, to better assess socio-economic outcomes, direct economic measures of well-being should be linked with other measures of well-being developed by other social science branches, such as sociology, demography, and psychology. Third, data observations should be reconciled with lifecycle models to investigate the causal mechanisms behind socio-economic outcomes. The main goal of the German Socio-Economic Panel (SOEP) is in line with the views and visions expressed in Angus Deaton’s lecture: Established in 1984 and located at the German Institute for Economic Research (DIW Berlin), SOEP serves a global research community by providing representative longitudinal data of private households in Germany. The SOEP’s primary research interests and the original survey concept was rooted in the multidisciplinary Collaborative Research Center SfB3, “Microanalytic Foundations of Social Policy” at the Universities of

573 citations


Journal ArticleDOI
24 Jul 2019-Nature
TL;DR: High-resolution spatial maps of the global abundance of soil nematodes and the composition of functional groups show that soil nematode are found in higher abundances in sub-Arctic regions, than in temperate or tropical regions.
Abstract: Soil organisms are a crucial part of the terrestrial biosphere. Despite their importance for ecosystem functioning, few quantitative, spatially explicit models of the active belowground community currently exist. In particular, nematodes are the most abundant animals on Earth, filling all trophic levels in the soil food web. Here we use 6,759 georeferenced samples to generate a mechanistic understanding of the patterns of the global abundance of nematodes in the soil and the composition of their functional groups. The resulting maps show that 4.4 ± 0.64 × 1020 nematodes (with a total biomass of approximately 0.3 gigatonnes) inhabit surface soils across the world, with higher abundances in sub-Arctic regions (38% of total) than in temperate (24%) or tropical (21%) regions. Regional variations in these global trends also provide insights into local patterns of soil fertility and functioning. These high-resolution models provide the first steps towards representing soil ecological processes in global biogeochemical models and will enable the prediction of elemental cycling under current and future climate scenarios.

552 citations


Journal ArticleDOI
Heather Orpana1, Heather Orpana2, Laurie B. Marczak3, Megha Arora3  +338 moreInstitutions (173)
06 Feb 2019-BMJ
TL;DR: Age standardised mortality rates for suicide have greatly reduced since 1990, but suicide remains an important contributor to mortality worldwide and can be targeted towards vulnerable populations if they are informed by variations in mortality rates.
Abstract: Objectives To use the estimates from the Global Burden of Disease Study 2016 to describe patterns of suicide mortality globally, regionally, and for 195 countries and territories by age, sex, and Socio-demographic index, and to describe temporal trends between 1990 and 2016. Design Systematic analysis. Main outcome measures Crude and age standardised rates from suicide mortality and years of life lost were compared across regions and countries, and by age, sex, and Socio-demographic index (a composite measure of fertility, income, and education). Results The total number of deaths from suicide increased by 6.7% (95% uncertainty interval 0.4% to 15.6%) globally over the 27 year study period to 817 000 (762 000 to 884 000) deaths in 2016. However, the age standardised mortality rate for suicide decreased by 32.7% (27.2% to 36.6%) worldwide between 1990 and 2016, similar to the decline in the global age standardised mortality rate of 30.6%. Suicide was the leading cause of age standardised years of life lost in the Global Burden of Disease region of high income Asia Pacific and was among the top 10 leading causes in eastern Europe, central Europe, western Europe, central Asia, Australasia, southern Latin America, and high income North America. Rates for men were higher than for women across regions, countries, and age groups, except for the 15 to 19 age group. There was variation in the female to male ratio, with higher ratios at lower levels of Socio-demographic index. Women experienced greater decreases in mortality rates (49.0%, 95% uncertainty interval 42.6% to 54.6%) than men (23.8%, 15.6% to 32.7%). Conclusions Age standardised mortality rates for suicide have greatly reduced since 1990, but suicide remains an important contributor to mortality worldwide. Suicide mortality was variable across locations, between sexes, and between age groups. Suicide prevention strategies can be targeted towards vulnerable populations if they are informed by variations in mortality rates.

472 citations


Journal ArticleDOI
TL;DR: In this article, the results for pseudo-critical temperatures of QCD chiral crossovers at zero and non-zero values of baryon (B), strangeness (S), electric charge (Q), and isospin (I) chemical potentials were obtained using lattice QCD calculations carried out with two degenerate up and down dynamical quarks and a dynamical strange quark, with quark masses corresponding to physical values of pion and kaon masses in the continuum limit.

394 citations


Journal ArticleDOI
TL;DR: The interlink of the physiological understanding of tolerance processes from molecular processes as well as the agronomical techniques for stabilizing growth and yield and their interlinks might help improving the authors' crops for future demand and will provide improvement for cultivating crops in saline environment.
Abstract: Thirty crop species provide 90% of our food, most of which display severe yield losses under moderate salinity. Securing and augmenting agricultural yield in times of global warming and population increase is urgent and should, aside from ameliorating saline soils, include attempts to increase crop plant salt tolerance. This short review provides an overview of the processes that limit growth and yield in saline conditions. Yield is reduced if soil salinity surpasses crop-specific thresholds, with cotton, barley and sugar beet being highly tolerant, while sweet potato, wheat and maize display high sensitivity. Apart from Na+ , also Cl- , Mg2+ , SO4 2- or HCO3 - contribute to salt toxicity. The inhibition of biochemical or physiological processes cause imbalance in metabolism and cell signalling and enhance the production of reactive oxygen species interfering with cell redox and energy state. Plant development and root patterning is disturbed, and this response depends on redox and reactive oxygen species signalling, calcium and plant hormones. The interlink of the physiological understanding of tolerance processes from molecular processes as well as the agronomical techniques for stabilizing growth and yield and their interlinks might help improving our crops for future demand and will provide improvement for cultivating crops in saline environment.

382 citations


Journal ArticleDOI
18 Apr 2019-Langmuir
TL;DR: An overview of the state-of-the-art, recent developments as well as emerging trends in the field of nano- and microgels is provided.
Abstract: Nanogels and microgels are soft, deformable, and penetrable objects with an internal gel-like structure that is swollen by the dispersing solvent. Their softness and the potential to respond to external stimuli like temperature, pressure, pH, ionic strength, and different analytes make them interesting as soft model systems in fundamental research as well as for a broad range of applications, in particular in the field of biological applications. Recent tremendous developments in their synthesis open access to systems with complex architectures and compositions allowing for tailoring microgels with specific properties. At the same time state-of-the-art theoretical and simulation approaches offer deeper understanding of the behavior and structure of nano- and microgels under external influences and confinement at interfaces or at high volume fractions. Developments in the experimental analysis of nano- and microgels have become particularly important for structural investigations covering a broad range of length scales relevant to the internal structure, the overall size and shape, and interparticle interactions in concentrated samples. Here we provide an overview of the state-of-the-art, recent developments as well as emerging trends in the field of nano- and microgels. The following aspects build the focus of our discussion: tailoring (multi)functionality through synthesis; the role in biological and biomedical applications; the structure and properties as a model system, e.g., for densely packed arrangements in bulk and at interfaces; as well as the theory and computer simulation.

354 citations


Journal ArticleDOI
06 Nov 2019-Nature
TL;DR: A roadmap for sex and gender analysis across scientific disciplines is provided and it is called on researchers, funding agencies, peer-reviewed journals and universities to coordinate efforts to implement robust methods of sex andGender analysis.
Abstract: The goal of sex and gender analysis is to promote rigorous, reproducible and responsible science. Incorporating sex and gender analysis into experimental design has enabled advancements across many disciplines, such as improved treatment of heart disease and insights into the societal impact of algorithmic bias. Here we discuss the potential for sex and gender analysis to foster scientific discovery, improve experimental efficiency and enable social equality. We provide a roadmap for sex and gender analysis across scientific disciplines and call on researchers, funding agencies, peer-reviewed journals and universities to coordinate efforts to implement robust methods of sex and gender analysis. The authors discuss the potential for sex and gender analysis to foster scientific discovery, improve experimental efficiency and enable social equality.

297 citations


Journal ArticleDOI
Timothy W. Shimwell1, Timothy W. Shimwell2, C. Tasse3, C. Tasse4, Martin J. Hardcastle5, A. P. Mechev2, Wendy L. Williams5, Philip Best6, Huub Röttgering2, Joseph R. Callingham1, T. J. Dijkema1, F. de Gasperin2, F. de Gasperin7, D. N. Hoang2, B. Hugo3, M. Mirmont, J. B. R. Oonk2, J. B. R. Oonk1, Isabella Prandoni8, D. A. Rafferty7, J. Sabater6, Oleg Smirnov3, R. J. van Weeren2, Glenn J. White9, Glenn J. White10, Marcellin Atemkeng3, L. Bester3, E. Bonnassieux11, Marcus Brüggen7, Gianfranco Brunetti8, Krzysztof T. Chyzy12, Rachel Cochrane6, John Conway13, Judith H. Croston10, A. Danezi, Kenneth Duncan2, Marijke Haverkorn14, George Heald15, Marco Iacobelli1, Huib Intema2, Neal Jackson16, Marek Jamrozy12, Matt J. Jarvis17, Matt J. Jarvis18, R. Lakhoo17, M. Mevius1, George K. Miley2, Leah K. Morabito17, R. Morganti1, R. Morganti19, D. Nisbet6, Emanuela Orru1, Simon Perkins, R. Pizzo1, C. Schrijvers, Daniel J. Smith5, R. C. Vermeulen1, Michael W. Wise20, Michael W. Wise1, L. Alegre6, David Bacon21, I. van Bemmel22, Robert Beswick16, Annalisa Bonafede8, Annalisa Bonafede7, A. Botteon23, A. Botteon8, Stephen Bourke13, Marisa Brienza19, Marisa Brienza1, G. Calistro Rivera2, Rossella Cassano8, A. O. Clarke16, Christopher J. Conselice24, R.-J. Dettmar25, A. Drabent, C. Dumba26, K. L. Emig2, Torsten A. Enßlin27, Chiara Ferrari28, M. A. Garrett16, M. A. Garrett2, Ricardo Genova-Santos29, Ricardo Genova-Santos30, Arti Goyal12, G. Gürkan15, C. L. Hale17, Jeremy J. Harwood5, Volker Heesen7, Matthias Hoeft, Cathy Horellou13, C. A. Jackson1, G. Kokotanekov20, R. Kondapally6, Magdalena Kunert-Bajraszewska, V. H. Mahatma5, Elizabeth K. Mahony15, Subhash C. Mandal2, John McKean1, John McKean19, Andrea Merloni27, Beatriz Mingo11, Arpad Miskolczi25, S. Mooney31, Błażej Nikiel-Wroczyński12, Shane O'Sullivan7, John L. Quinn31, Wolfgang Reich27, C. Roskowinski, Antonia Rowlinson20, Antonia Rowlinson1, F. Savini7, A. Saxena2, Dominik J. Schwarz32, Aleksandar Shulevski20, Aleksandar Shulevski1, S. S. Sridhar1, H. R. Stacey1, H. R. Stacey19, S. Urquhart10, M. H. D. van der Wiel1, Eskil Varenius16, Eskil Varenius13, B. Webster10, A. Wilber7 
TL;DR: The LOFAR Two-metre Sky Survey (LoTSS) is an ongoing sensitive, high-resolution 120-168 MHz survey of the entire northern sky for which observations are now 20% complete as discussed by the authors.
Abstract: The LOFAR Two-metre Sky Survey (LoTSS) is an ongoing sensitive, high-resolution 120–168 MHz survey of the entire northern sky for which observations are now 20% complete. We present our first full-quality public data release. For this data release 424 square degrees, or 2% of the eventual coverage, in the region of the HETDEX Spring Field (right ascension 10h45m00s to 15h30m00s and declination 45°00′00″ to 57°00′00″) were mapped using a fully automated direction-dependent calibration and imaging pipeline that we developed. A total of 325 694 sources are detected with a signal of at least five times the noise, and the source density is a factor of ∼10 higher than the most sensitive existing very wide-area radio-continuum surveys. The median sensitivity is S 144 MHz = 71 μ Jy beam−1 and the point-source completeness is 90% at an integrated flux density of 0.45 mJy. The resolution of the images is 6″ and the positional accuracy is within 0.2″. This data release consists of a catalogue containing location, flux, and shape estimates together with 58 mosaic images that cover the catalogued area. In this paper we provide an overview of the data release with a focus on the processing of the LOFAR data and the characteristics of the resulting images. In two accompanying papers we provide the radio source associations and deblending and, where possible, the optical identifications of the radio sources together with the photometric redshifts and properties of the host galaxies. These data release papers are published together with a further ∼20 articles that highlight the scientific potential of LoTSS.

277 citations


Journal ArticleDOI
TL;DR: The concept of entrainment is discussed, which offers both a putative neurophysiological mechanism for selective listening and a versatile window onto the neural basis of hearing and speech comprehension.

257 citations


Journal ArticleDOI
TL;DR: This work analysed gaps in the two most important reference databases, Barcode of Life Data Systems (BOLD) and NCBI GenBank, with a focus on the taxa most frequently used in WFD and MSFD, and found that coverage varies strongly among taxonomic groups, and among geographic regions.

Journal ArticleDOI
TL;DR: This work presents a meta-analyses of the determinants of infectious disease in eight operation rooms of the immune system and three of them are connected to each other through the immune response to infectious disease.

Journal ArticleDOI
TL;DR: MOLI, a multi-omics late integration method based on deep neural networks, achieves higher prediction accuracy in external validations and its high predictive power suggests it may have utility in precision oncology.
Abstract: Motivation Historically, gene expression has been shown to be the most informative data for drug response prediction. Recent evidence suggests that integrating additional omics can improve the prediction accuracy which raises the question of how to integrate the additional omics. Regardless of the integration strategy, clinical utility and translatability are crucial. Thus, we reasoned a multi-omics approach combined with clinical datasets would improve drug response prediction and clinical relevance. Results We propose MOLI, a multi-omics late integration method based on deep neural networks. MOLI takes somatic mutation, copy number aberration and gene expression data as input, and integrates them for drug response prediction. MOLI uses type-specific encoding sub-networks to learn features for each omics type, concatenates them into one representation and optimizes this representation via a combined cost function consisting of a triplet loss and a binary cross-entropy loss. The former makes the representations of responder samples more similar to each other and different from the non-responders, and the latter makes this representation predictive of the response values. We validate MOLI on in vitro and in vivo datasets for five chemotherapy agents and two targeted therapeutics. Compared to state-of-the-art single-omics and early integration multi-omics methods, MOLI achieves higher prediction accuracy in external validations. Moreover, a significant improvement in MOLI's performance is observed for targeted drugs when training on a pan-drug input, i.e. using all the drugs with the same target compared to training only on drug-specific inputs. MOLI's high predictive power suggests it may have utility in precision oncology. Availability and implementation https://github.com/hosseinshn/MOLI. Supplementary information Supplementary data are available at Bioinformatics online.

Journal ArticleDOI
Roy Burstein1, Nathaniel J Henry1, Michael Collison1, Laurie B. Marczak1  +663 moreInstitutions (290)
16 Oct 2019-Nature
TL;DR: A high-resolution, global atlas of mortality of children under five years of age between 2000 and 2017 highlights subnational geographical inequalities in the distribution, rates and absolute counts of child deaths by age.
Abstract: Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations.

Journal ArticleDOI
TL;DR: The challenges faced in EQ-5D-5L valuation since 2012 are presented and how these were resolved and a set of new challenges that have become central in currently ongoing research on how EQ-4D-4L health states should be valued and modeled are described.

Journal ArticleDOI
TL;DR: A lattice-QCD-based determination of the chiral phase transition temperature in QCD with two degenerate, massless quarks and a physical strange quark mass is presented using lattice QCD calculations with the highly improved staggered quarks action.
Abstract: We present a lattice-QCD-based determination of the chiral phase transition temperature in QCD with two degenerate, massless quarks and a physical strange quark mass using lattice QCD calculations with the highly improved staggered quarks action. We propose and calculate two novel estimators for the chiral transition temperature for several values of the light quark masses, corresponding to Goldstone pion masses in the range of $58\text{ }\text{ }\mathrm{MeV}\ensuremath{\lesssim}{m}_{\ensuremath{\pi}}\ensuremath{\lesssim}163\text{ }\text{ }\mathrm{MeV}$. The chiral phase transition temperature is determined by extrapolating to vanishing pion mass using universal scaling analysis. Finite-volume effects are controlled by extrapolating to the thermodynamic limit using spatial lattice extents in the range of 2.8--4.5 times the inverse of the pion mass. Continuum extrapolations are carried out by using three different values of the lattice cutoff, corresponding to lattices with temporal extents ${N}_{\ensuremath{\tau}}=6$, 8, and 12. After thermodynamic, continuum, and chiral extrapolations, we find the chiral phase transition temperature ${T}_{c}^{0}=13{2}_{\ensuremath{-}6}^{+3}\text{ }\text{ }\mathrm{MeV}$.

Journal ArticleDOI
TL;DR: In this paper, a comprehensive literature review was conducted to examine the impact of micro-and nano-sized plastics on benthic invertebrates, including the physical and chemical effects of leaching and the interactions of plastic particles with contaminants.
Abstract: As documented by the numerous publications that have appeared in recent years, plastic pollution of the environment and the effects on the respective ecosystems are currently one of the most intensely discussed issues in environmental science and in society at large. Of special concern are the effects of micro- and nano-sized plastics. A key issue in understanding the fate and potential effects of micro- and nano-sized plastics is their dynamic nature, as the size, shape, and charge of the particles change over time. Moreover, due to various biological processes, such as the aggregation of organic material and/or bacteria (“biofouling”), the density of plastic particles that settle in the sediments of aquatic ecosystems may be several orders of magnitudes higher than that in the surrounding waters. Consequently, the risk posed by plastic pollution to benthic fauna is considerably high. Nonetheless, the vast majority of studies examining the effects of microplastics have focused on pelagic organisms so far. We therefore conducted a comprehensive literature review to examine the impact of micro- and nano-sized plastics on benthic invertebrates, including the physical and chemical effects of leaching and the interactions of plastic particles with contaminants. Overall, 330 papers were reviewed for their fulfilment of different criteria (e.g. test species, plastic material, particle shape, particle size, exposure concentration, exposure route, assay type, assay duration), with 49 publications finally included in our survey. A comprehensive gap-analysis on the effects of plastic particles on benthic invertebrates, revealed a wide variety of effects triggered by micro- and/or nano-sized plastics but also distinct differences regarding the plastic materials tested, the size fractions applied, the shape of the respective particles and the exposure routes tested. Our review concludes with a discussion of the important research gaps concerning freshwater ecosystems and recommendations for future areas of research.

Journal ArticleDOI
TL;DR: In this article, the authors consider a Brownian particle which, in addition to being in contact with a thermal bath, is driven by fluctuating forces which stem from active processes in the system, such as self-propulsion o...
Abstract: We consider a Brownian particle which, in addition to being in contact with a thermal bath, is driven by fluctuating forces which stem from active processes in the system, such as self-propulsion o ...

Journal ArticleDOI
01 Mar 2019-BMJ Open
TL;DR: It is highlighted that the collection, reporting and analysis of AE data in clinical trials is inconsistent and RCTs as a source of safety data are underused.
Abstract: Objective To ascertain contemporary approaches to the collection, reporting and analysis of adverse events (AEs) in randomised controlled trials (RCTs) with a primary efficacy outcome. Design A review of clinical trials of drug interventions from four high impact medical journals. Data sources Electronic contents table of the BMJ, the Journal of the American Medical Association (JAMA), the Lancet and the New England Journal of Medicine (NEJM) were searched for reports of original RCTs published between September 2015 and September 2016. Methods A prepiloted checklist was used and single data extraction was performed by three reviewers with independent check of a randomly sampled subset to verify quality. We extracted data on collection methods, assessment of severity and causality, reporting criteria, analysis methods and presentation of AE data. Results We identified 184 eligible reports (BMJ n=3; JAMA n=38, Lancet n=62 and NEJM n=81). Sixty-two per cent reported some form of spontaneous AE collection but only 29% included details of specific prompts used to ascertain AE data. Numbers that withdrew from the trial were well reported (80%), however only 35% of these reported whether withdrawals were due to AEs. Results presented and analysis performed was predominantly on ‘patients with at least one event’ with 84% of studies ignoring repeated events. Despite a lack of power to undertake formal hypothesis testing, 47% performed such tests for binary outcomes. Conclusions This review highlighted that the collection, reporting and analysis of AE data in clinical trials is inconsistent and RCTs as a source of safety data are underused. Areas to improve include reducing information loss when analysing at patient level and inappropriate practice of underpowered multiple hypothesis testing. Implementation of standard reporting practices could enable a more accurate synthesis of safety data and development of guidance for statistical methodology to assess causality of AEs could facilitate better statistical practice.

Journal ArticleDOI
TL;DR: There is neither a consistent understanding of the construct of financial burden nor do available instruments cover all relevant aspects of a patients’ distress perception, so it is difficult to compare and quantify the prevalence of financial distress.

Journal ArticleDOI
05 Jun 2019-Neuron
TL;DR: Analysis of time- and source-resolved human magnetoencephalographic data reveals a systematic spatiotemporal cascade of the relevant computations, starting with early segregated unisensory representations, continuing with sensory fusion in parietal-temporal regions, and culminating as causal inference in the frontal lobe.

Journal ArticleDOI
TL;DR: CAMISIM can simulate a wide variety of microbial communities and metagenome data sets together with standards of truth for method evaluation, and generated the benchmark data sets of the first CAMI challenge.
Abstract: Shotgun metagenome data sets of microbial communities are highly diverse, not only due to the natural variation of the underlying biological systems, but also due to differences in laboratory protocols, replicate numbers, and sequencing technologies. Accordingly, to effectively assess the performance of metagenomic analysis software, a wide range of benchmark data sets are required. We describe the CAMISIM microbial community and metagenome simulator. The software can model different microbial abundance profiles, multi-sample time series, and differential abundance studies, includes real and simulated strain-level diversity, and generates second- and third-generation sequencing data from taxonomic profiles or de novo. Gold standards are created for sequence assembly, genome binning, taxonomic binning, and taxonomic profiling. CAMSIM generated the benchmark data sets of the first CAMI challenge. For two simulated multi-sample data sets of the human and mouse gut microbiomes, we observed high functional congruence to the real data. As further applications, we investigated the effect of varying evolutionary genome divergence, sequencing depth, and read error profiles on two popular metagenome assemblers, MEGAHIT, and metaSPAdes, on several thousand small data sets generated with CAMISIM. CAMISIM can simulate a wide variety of microbial communities and metagenome data sets together with standards of truth for method evaluation. All data sets and the software are freely available at https://github.com/CAMI-challenge/CAMISIM

Journal ArticleDOI
TL;DR: The CRISPR-BEST approach is a significant improvement over existing genetic manipulation methods to engineer streptomycetes, especially for those strains that cannot be genome-edited using normal DSB-based genome editing systems, such as CRISpr-Cas9.
Abstract: Streptomycetes serve as major producers of various pharmacologically and industrially important natural products. Although CRISPR-Cas9 systems have been developed for more robust genetic manipulations, concerns of genome instability caused by the DNA double-strand breaks (DSBs) and the toxicity of Cas9 remain. To overcome these limitations, here we report development of the DSB-free, single-nucleotide-resolution genome editing system CRISPR-BEST (CRISPR-Base Editing SysTem), which comprises a cytidine (CRISPR-cBEST) and an adenosine (CRISPR-aBEST) deaminase-based base editor. Specifically targeted by an sgRNA, CRISPR-cBEST can efficiently convert a C:G base pair to a T:A base pair and CRISPR-aBEST can convert an A:T base pair to a G:C base pair within a window of approximately 7 and 6 nucleotides, respectively. CRISPR-BEST was validated and successfully used in different Streptomyces species. Particularly in nonmodel actinomycete Streptomyces collinus Tu365, CRISPR-cBEST efficiently inactivated the 2 copies of kirN gene that are in the duplicated kirromycin biosynthetic pathways simultaneously by STOP codon introduction. Generating such a knockout mutant repeatedly failed using the conventional DSB-based CRISPR-Cas9. An unbiased, genome-wide off-target evaluation indicates the high fidelity and applicability of CRISPR-BEST. Furthermore, the system supports multiplexed editing with a single plasmid by providing a Csy4-based sgRNA processing machinery. To simplify the protospacer identification process, we also updated the CRISPy-web (https://crispy.secondarymetabolites.org), and now it allows designing sgRNAs specifically for CRISPR-BEST applications.

Journal ArticleDOI
TL;DR: In this paper, the authors present the source associations and optical and/or IR identifications for sources in the first data release, which are made using a combination of statistical techniques and visual association and identification.
Abstract: The LOFAR Two-metre Sky Survey (LoTSS) is an ongoing sensitive, high-resolution 120–168 MHz survey of the northern sky with diverse and ambitious science goals. Many of the scientific objectives of LoTSS rely upon, or are enhanced by, the association or separation of the sometimes incorrectly catalogued radio components into distinct radio sources and the identification and characterisation of the optical counterparts to these sources. We present the source associations and optical and/or IR identifications for sources in the first data release, which are made using a combination of statistical techniques and visual association and identification. We document in detail the colour- and magnitude-dependent likelihood ratio method used for statistical identification as well as the Zooniverse project, called LOFAR Galaxy Zoo, used for visual classification. We describe the process used to select which of these two different methods is most appropriate for each LoTSS source. The final LoTSS-DR1-IDs value-added catalogue presented contains 318 520 radio sources, of which 231 716 (73%) have optical and/or IR identifications in Pan-STARRS and WISE.

Journal ArticleDOI
TL;DR: A greater appreciation of the extent of variation in aposematic species, and of the selective pressures and constraints which contribute to this once‐paradoxical phenomenon, yields a new perspective for the field of Aposematic signalling.
Abstract: Aposematic theory has historically predicted that predators should select for warning signals to converge on a single form, as a result of frequency-dependent learning However, widespread variation in warning signals is observed across closely related species, populations and, most problematically for evolutionary biologists, among individuals in the same population Recent research has yielded an increased awareness of this diversity, challenging the paradigm of signal monomorphy in aposematic animals Here we provide a comprehensive synthesis of these disparate lines of investigation, identifying within them three broad classes of explanation for variation in aposematic warning signals: genetic mechanisms, differences among predators and predator behaviour, and alternative selection pressures upon the signal The mechanisms producing warning coloration are also important Detailed studies of the genetic basis of warning signals in some species, most notably Heliconius butterflies, are beginning to shed light on the genetic architecture facilitating or limiting key processes such as the evolution and maintenance of polymorphisms, hybridisation, and speciation Work on predator behaviour is changing our perception of the predator community as a single homogenous selective agent, emphasising the dynamic nature of predator-prey interactions Predator variability in a range of factors (eg perceptual abilities, tolerance to chemical defences, and individual motivation), suggests that the role of predators is more complicated than previously appreciated With complex selection regimes at work, polytypisms and polymorphisms may even occur in Mullerian mimicry systems Meanwhile, phenotypes are often multifunctional, and thus subject to additional biotic and abiotic selection pressures Some of these selective pressures, primarily sexual selection and thermoregulation, have received considerable attention, while others, such as disease risk and parental effects, offer promising avenues to explore As well as reviewing the existing evidence from both empirical studies and theoretical modelling, we highlight hypotheses that could benefit from further investigation in aposematic species Finally by collating known instances of variation in warning signals, we provide a valuable resource for understanding the taxonomic spread of diversity in aposematic signalling and with which to direct future research A greater appreciation of the extent of variation in aposematic species, and of the selective pressures and constraints which contribute to this once-paradoxical phenomenon, yields a new perspective for the field of aposematic signalling

Proceedings ArticleDOI
11 Mar 2019
TL;DR: It is demonstrated that children are able to acquire and retain English vocabulary words taught by a robot tutor to a similar extent as when they are taught by an tablet application.
Abstract: We present a large-scale study of a series of seven lessons designed to help young children learn English vocabulary as a foreign language using a social robot. The experiment was designed to investigate 1) the effectiveness of a social robot teaching children new words over the course of multiple interactions (supported by a tablet), 2) the added benefit of a robot's iconic gestures on word learning and retention, and 3) the effect of learning from a robot tutor accompanied by a tablet versus learning from a tablet application alone. For reasons of transparency, the research questions, hypotheses and methods were preregistered. With a sample size of 194 children, our study was statistically well-powered. Our findings demonstrate that children are able to acquire and retain English vocabulary words taught by a robot tutor to a similar extent as when they are taught by a tablet application. In addition, we found no beneficial effect of a robot's iconic gestures on learning gains.

Journal ArticleDOI
TL;DR: The authors optimise both acquisition and reconstruction software to achieve multicolour SR-SIM at video frame-rates with reconstructed images displaying with only milliseconds delay during the experiment, a first in super-resolved structured illumination microscopy.
Abstract: Super-resolved structured illumination microscopy (SR-SIM) is among the fastest fluorescence microscopy techniques capable of surpassing the optical diffraction limit. Current custom-build instruments are able to deliver two-fold resolution enhancement with high acquisition speed. SR-SIM is usually a two-step process, with raw-data acquisition and subsequent, time-consuming post-processing for image reconstruction. In contrast, wide-field and (multi-spot) confocal techniques produce high-resolution images instantly. Such immediacy is also possible with SR-SIM, by tight integration of a video-rate capable SIM with fast reconstruction software. Here we present instant SR-SIM by VIGOR (Video-rate Immediate GPU-accelerated Open-Source Reconstruction). We demonstrate multi-color SR-SIM at video frame-rates, with less than 250 ms delay between measurement and reconstructed image display. This is achieved by modifying and extending high-speed SR-SIM image acquisition with a new, GPU-enhanced, network-enabled image-reconstruction software. We demonstrate high-speed surveying of biological samples in multiple colors and live imaging of moving mitochondria as an example of intracellular dynamics. Sequential acquisition and image reconstruction in super-resolved structured illumination microscopy (SR-SIM) is time-consuming. Here the authors optimise both acquisition and reconstruction software to achieve multicolour SR-SIM at video frame-rates with reconstructed images displaying with only milliseconds delay during the experiment.

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TL;DR: This study provides new insight into OER electrocatalysis: Before onset of the O-O bond formation step, the catalytic oxyhydroxide has accumulated electron deficiencies by both, oxidation of transition metal ions and formation of partially oxidized oxygen sites.
Abstract: In-situ X-ray absorption spectroscopy (XAS) at the oxygen K-edge was used to investigate the role of oxygen during the oxygen evolution reaction (OER) in an electrodeposited Ni-Fe(OxHy) electrocatalyst in alkaline pH. We show the rise of a pre-peak feature at 529 eV in the O K-edge spectra, correlated to the appearance of a shoulder at the Ni L3-edge and formation of oxidized Ni3+/4+-O. Then, for the first time, we track the spectral changes in a dynamic fashion in both the soft and hard X-ray regimes during cyclic voltammetry (in situ CV-XAS) to obtain a fine-tuned resolution of the potential-related changes. The pre-peak feature at the O K-edge likely signifies formation of an electron deficient oxygen site. The electrophilic oxygen species appears and disappears reversibly in correlation with the Ni2+ ↔ Ni3+/4+ process, and persists during OER catalysis as long the metal is oxidized. Our study provides new insight into OER electrocatalysis: Before onset of the O-O bond formation step, the catalytic oxyhydroxide has accumulated electron deficiencies by both, oxidation of transition metal ions and formation of partially oxidized oxygen sites.

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TL;DR: An overview of the state of the art in research on the aetiology and treatment of nightmare disorder and further perspectives on these issues are outlined and some future perspectives and potential further developments of nightmare treatments and research into nightmare aetology are highlighted.
Abstract: This consensus paper provides an overview of the state of the art in research on the aetiology and treatment of nightmare disorder and outlines further perspectives on these issues. It presents a definition of nightmares and nightmare disorder followed by epidemiological findings, and then explains existing models of nightmare aetiology in traumatized and non-traumatized individuals. Chronic nightmares develop through the interaction of elevated hyperarousal and impaired fear extinction. This interplay is assumed to be facilitated by trait affect distress elicited by traumatic experiences, early childhood adversity and trait susceptibility, as well as by elevated thought suppression and potentially sleep-disordered breathing. Accordingly, different treatment options for nightmares focus on their meaning, on the chronic repetition of the nightmare or on maladaptive beliefs. Clinically, knowledge of healthcare providers about nightmare disorder and the delivery of evidence-based interventions in the healthcare system is discussed. Based on these findings, we highlight some future perspectives and potential further developments of nightmare treatments and research into nightmare aetiology.

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TL;DR: In this article, the authors test three aspects of strong equivalence principle (SEP) using observed change rates in the orbital period and eccentricity of binary pulsar J1713+0747: (1) the gravitational constant constancy as part of locational invariance of gravitation; (2) the universality of free fall (UFF) for strongly self-gravitating bodies; (3) the post-Newtonian parameter |$\hat{\alpha }_3$| in gravitational Lorentz invariance.
Abstract: Symmetries play a fundamental role in modern theories of gravity. The strong equivalence principle (SEP) constitutes a collection of gravitational symmetries which are all implemented by general relativity. Alternative theories, however, are generally expected to violate some aspects of SEP. We test three aspects of SEP using observed change rates in the orbital period and eccentricity of binary pulsar J1713+0747: (1) the gravitational constant’s constancy as part of locational invariance of gravitation; (2) the universality of free fall (UFF) for strongly self-gravitating bodies; (3) the post-Newtonian parameter |$\hat{\alpha }_3$| in gravitational Lorentz invariance. Based on the pulsar timing result of the combined data set from the North American Nanohertz Gravitational Observatory and the European Pulsar Timing Array, we find |$\dot{G}/G = (-0.1 \pm 0.9) \times 10^{-12}\, {\rm yr}^{-1}$|⁠, which is weaker than Solar system limits, but applies for strongly self-gravitating objects. Furthermore, we obtain an improved test for a UFF violation by a strongly self-gravitating mass falling in the gravitational field of our Galaxy, with a limit of |Δ| < 0.002 (95 per cent C.L.). Finally, we derive an improved limit on the self-acceleration of a gravitationally bound rotating body, to a preferred reference frame in the Universe, with |$-3\times 10^{-20} \lt \hat{\alpha }_3 \lt 4\times 10^{-20}$| (95 per cent C.L.). These results are based on direct UFF and |$\hat{\alpha }_3$| tests using pulsar binaries, and they overcome various limitations of previous tests of this kind.