Showing papers by "University of Göttingen published in 2017"
Theo Vos1, Amanuel Alemu Abajobir, Kalkidan Hassen Abate2, Cristiana Abbafati3 +775 more•Institutions (305)
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016.
10,401 citations
TL;DR: In this article, the authors presented the CHELSA (Climatologies at high resolution for the earth's land surface areas) data of downscaled model output temperature and precipitation estimates of the ERA-Interim climatic reanalysis to a high resolution of 30'arc'sec.
Abstract: High-resolution information on climatic conditions is essential to many applications in environmental and ecological sciences. Here we present the CHELSA (Climatologies at high resolution for the earth’s land surface areas) data of downscaled model output temperature and precipitation estimates of the ERA-Interim climatic reanalysis to a high resolution of 30 arc sec. The temperature algorithm is based on statistical downscaling of atmospheric temperatures. The precipitation algorithm incorporates orographic predictors including wind fields, valley exposition, and boundary layer height, with a subsequent bias correction. The resulting data consist of a monthly temperature and precipitation climatology for the years 1979–2013. We compare the data derived from the CHELSA algorithm with other standard gridded products and station data from the Global Historical Climate Network. We compare the performance of the new climatologies in species distribution modelling and show that we can increase the accuracy of species range predictions. We further show that CHELSA climatological data has a similar accuracy as other products for temperature, but that its predictions of precipitation patterns are better. Machine-accessible metadata file describing the reported data (ISA-Tab format)
1,859 citations
TL;DR: The InTBIR Participants and Investigators have provided informed consent for the study to take place in Poland.
Abstract: Additional co-authors: Endre Czeiter, Marek Czosnyka, Ramon Diaz-Arrastia, Jens P Dreier, Ann-Christine Duhaime, Ari Ercole, Thomas A van Essen, Valery L Feigin, Guoyi Gao, Joseph Giacino, Laura E Gonzalez-Lara, Russell L Gruen, Deepak Gupta, Jed A Hartings, Sean Hill, Ji-yao Jiang, Naomi Ketharanathan, Erwin J O Kompanje, Linda Lanyon, Steven Laureys, Fiona Lecky, Harvey Levin, Hester F Lingsma, Marc Maegele, Marek Majdan, Geoffrey Manley, Jill Marsteller, Luciana Mascia, Charles McFadyen, Stefania Mondello, Virginia Newcombe, Aarno Palotie, Paul M Parizel, Wilco Peul, James Piercy, Suzanne Polinder, Louis Puybasset, Todd E Rasmussen, Rolf Rossaint, Peter Smielewski, Jeannette Soderberg, Simon J Stanworth, Murray B Stein, Nicole von Steinbuchel, William Stewart, Ewout W Steyerberg, Nino Stocchetti, Anneliese Synnot, Braden Te Ao, Olli Tenovuo, Alice Theadom, Dick Tibboel, Walter Videtta, Kevin K W Wang, W Huw Williams, Kristine Yaffe for the InTBIR Participants and Investigators
1,354 citations
University of Vienna1, University of Oldenburg2, Zoological Society of London3, University College London4, International Union for Conservation of Nature and Natural Resources5, Lincoln University (New Zealand)6, Free University of Berlin7, Leibniz Association8, University of Auckland9, Academy of Sciences of the Czech Republic10, Charles University in Prague11, Stellenbosch University12, National and Kapodistrian University of Athens13, University of Fribourg14, University of Sassari15, University of Porto16, Sapienza University of Rome17, University of Konstanz18, Durham University19, University of Concepción20, Charles Darwin Foundation21, CABI22, University of Göttingen23, Martin Luther University of Halle-Wittenberg24, Helmholtz Centre for Environmental Research - UFZ25, United States Forest Service26, Bielefeld University27, Botanical Society of Britain and Ireland28, Environment Agency29, National Museum of Natural History30, Institut national de la recherche agronomique31, University of Silesia in Katowice32
TL;DR: In this paper, the authors used a database of 45,813 first records of 16,926 established alien species and showed that the annual rate of first records worldwide has increased during the last 200 years, with 37% of all first records reported most recently (1970-2014).
Abstract: Although research on human-mediated exchanges of species has substantially intensified during the last centuries, we know surprisingly little about temporal dynamics of alien species accumulations across regions and taxa. Using a novel database of 45,813 first records of 16,926 established alien species, we show that the annual rate of first records worldwide has increased during the last 200 years, with 37% of all first records reported most recently (1970-2014). Inter-continental and inter-taxonomic variation can be largely attributed to the diaspora of European settlers in the nineteenth century and to the acceleration in trade in the twentieth century. For all taxonomic groups, the increase in numbers of alien species does not show any sign of saturation and most taxa even show increases in the rate of first records over time. This highlights that past efforts to mitigate invasions have not been effective enough to keep up with increasing globalization.
1,301 citations
German Center for Neurodegenerative Diseases1, National and Kapodistrian University of Athens2, University of Göttingen3, University of Barcelona4, Centre national de la recherche scientifique5, University of Bordeaux6, King's College7, UCL Institute of Neurology8, University of Paris9, Mayo Clinic10, Paracelsus Private Medical University of Salzburg11, Rutgers University12
TL;DR: Clinical diagnostic criteria, published in 1996 by the National Institute of Neurological Disorders and Stroke/Society for PSP have excellent specificity, but their sensitivity is limited for variant PSP syndromes with presentations other than Richardson's syndrome.
Abstract: Background: PSP is a neuropathologically defined disease entity. Clinical diagnostic criteria, published in 1996 by the National Institute of Neurological Disorders and Stroke/Society for PSP, have excellent specificity, but their sensitivity is limited for variant PSP syndromes with presentations other than Richardson's syndrome. Objective: We aimed to provide an evidence- and consensus-based revision of the clinical diagnostic criteria for PSP. Methods: We searched the PubMed, Cochrane, Medline, and PSYCInfo databases for articles published in English since 1996, using postmortem diagnosis or highly specific clinical criteria as the diagnostic standard. Second, we generated retrospective standardized clinical data from patients with autopsy-confirmed PSP and control diseases. On this basis, diagnostic criteria were drafted, optimized in two modified Delphi evaluations, submitted to structured discussions with consensus procedures during a 2-day meeting, and refined in three further Delphi rounds. Results: Defined clinical, imaging, laboratory, and genetic findings serve as mandatory basic features, mandatory exclusion criteria, or context-dependent exclusion criteria. We identified four functional domains (ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction) as clinical predictors of PSP. Within each of these domains, we propose three clinical features that contribute different levels of diagnostic certainty. Specific combinations of these features define the diagnostic criteria, stratified by three degrees of diagnostic certainty (probable PSP, possible PSP, and suggestive of PSP). Clinical clues and imaging findings represent supportive features. Conclusions: Here, we present new criteria aimed to optimize early, sensitive, and specific clinical diagnosis of PSP on the basis of currently available evidence.
1,247 citations
Paris 12 Val de Marne University1, University of Göttingen2, University Hospital of Lausanne3, French Institute of Health and Medical Research4, University of Milan5, University of Otago6, University of Regensburg7, University of Marburg8, Ruhr University Bochum9, Ludwig Maximilian University of Munich10, University of Siena11, University of Texas at Dallas12, University of Tübingen13
TL;DR: It remains to be clarified whether the probable or possible therapeutic effects of tDCS are clinically meaningful and how to optimally perform tDCS in a therapeutic setting.
1,062 citations
University of Marburg1, University of Erlangen-Nuremberg2, Rovira i Virgili University3, Max Planck Society4, University of Göttingen5, University of California, Los Angeles6, International School for Advanced Studies7, University of Melbourne8, University of Trieste9, Ikerbasque10, University of Toronto11, Nanyang Technological University12, National Institutes of Health13, Stanford University14, Shanghai Jiao Tong University15, Tongji University16, University of Seville17, Karolinska Institutet18, Drexel University19, Sichuan University20, Rice University21, Northwestern University22, University of Basel23, Zhejiang University24, Heidelberg University25, University of Tokyo26, Harvard University27, University of Utah28, University of Michigan29, Swiss Federal Laboratories for Materials Science and Technology30, Seoul National University31, Saarland University32, Columbia University33, Chinese Academy of Sciences34, Kazan Federal University35, Emory University36, University of California, Irvine37, Autonomous University of Barcelona38, University of Massachusetts Amherst39, Pennsylvania State University40, Ghent University41, Imperial College London42, National Tsing Hua University43, South China University of Technology44, University of Ulm45, Hebrew University of Jerusalem46, Huazhong University of Science and Technology47, Peking University48
TL;DR: An overview of recent developments in nanomedicine is provided and the current challenges and upcoming opportunities for the field are highlighted and translation to the clinic is highlighted.
Abstract: The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic.
926 citations
University of Mainz1, University of Freiburg2, University of Würzburg3, Federal Institute for Drugs and Medical Devices4, RWTH Aachen University5, University of Regensburg6, University of Göttingen7, University of Tübingen8, Innsbruck Medical University9, University of Bern10, Ludwig Maximilian University of Munich11, Technische Universität München12, Max Planck Society13, University of Lausanne14
TL;DR: Following the new guidelines for therapeutic drug monitoring in psychiatry holds the potential to improve neuropsychopharmacotherapy, accelerate the recovery of many patients, and reduce health care costs.
Abstract: Therapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood to optimize pharmacotherapy. It considers the interindividual variability of pharmacokinetics and thus enables personalized pharmacotherapy. In psychiatry and neurology, patient populations that may particularly benefit from TDM are children and adolescents, pregnant women, elderly patients, individuals with intellectual disabilities, patients with substance abuse disorders, forensic psychiatric patients or patients with known or suspected pharmacokinetic abnormalities. Non-response at therapeutic doses, uncertain drug adherence, suboptimal tolerability, or pharmacokinetic drug-drug interactions are typical indications for TDM. However, the potential benefits of TDM to optimize pharmacotherapy can only be obtained if the method is adequately integrated in the clinical treatment process. To supply treating physicians and laboratories with valid information on TDM, the TDM task force of the Arbeitsgemeinschaft fur Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued their first guidelines for TDM in psychiatry in 2004. After an update in 2011, it was time for the next update. Following the new guidelines holds the potential to improve neuropsychopharmacotherapy, accelerate the recovery of many patients, and reduce health care costs.
827 citations
TL;DR: This study examined and compared the performances of the RF, kNN, and SVM classifiers for land use/cover classification using Sentinel-2 image data and found that SVM produced the highest OA with the least sensitivity to the training sample sizes.
Abstract: In previous classification studies, three non-parametric classifiers, Random Forest (RF), k-Nearest Neighbor (kNN), and Support Vector Machine (SVM), were reported as the foremost classifiers at producing high accuracies. However, only a few studies have compared the performances of these classifiers with different training sample sizes for the same remote sensing images, particularly the Sentinel-2 Multispectral Imager (MSI). In this study, we examined and compared the performances of the RF, kNN, and SVM classifiers for land use/cover classification using Sentinel-2 image data. An area of 30 × 30 km2 within the Red River Delta of Vietnam with six land use/cover types was classified using 14 different training sample sizes, including balanced and imbalanced, from 50 to over 1250 pixels/class. All classification results showed a high overall accuracy (OA) ranging from 90% to 95%. Among the three classifiers and 14 sub-datasets, SVM produced the highest OA with the least sensitivity to the training sample sizes, followed consecutively by RF and kNN. In relation to the sample size, all three classifiers showed a similar and high OA (over 93.85%) when the training sample size was large enough, i.e., greater than 750 pixels/class or representing an area of approximately 0.25% of the total study area. The high accuracy was achieved with both imbalanced and balanced datasets.
777 citations
Christian R. Marshall, Daniel P. Howrigan1, Daniel P. Howrigan2, Daniele Merico +326 more•Institutions (98)
TL;DR: In this article, a centralized analysis pipeline was applied to a SCZ cohort of 21,094 cases and 20,227 controls, and a global enrichment of copy number variants (CNVs) was observed in cases (odds ratio (OR) = 1.11, P = 5.7 × 10-15), which persisted after excluding loci implicated in previous studies.
Abstract: Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (odds ratio (OR) = 1.11, P = 5.7 × 10-15), which persisted after excluding loci implicated in previous studies (OR = 1.07, P = 1.7 × 10-6). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 × 10-11) and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 × 10-5). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by nonallelic homologous recombination.
774 citations
VU University Medical Center1, University of Southern California2, Max Planck Society3, McMaster University4, University of Adelaide5, University of California, Irvine6, Erasmus University Rotterdam7, Delft University of Technology8, Erasmus University Medical Center9, German Center for Neurodegenerative Diseases10, Greifswald University Hospital11, University of Münster12, University of Marburg13, QIMR Berghofer Medical Research Institute14, University of Queensland15, Queensland University of Technology16, Virginia Commonwealth University17, University of Göttingen18, University Hospital Heidelberg19, University of Sydney20, Otto-von-Guericke University Magdeburg21, Trinity College, Dublin22, University of Regensburg23, University Medical Center Groningen24, Leiden University Medical Center25, University of Melbourne26, University of Texas Health Science Center at Houston27, Charité28, University of Bonn29, University of Lübeck30, University Medical Center Freiburg31, Stanford University32, University of Calgary33, Warneford Hospital34, Royal Edinburgh Hospital35, University of Edinburgh36, University of Bern37, Cardiff University38, Leibniz Institute for Neurobiology39, University of Tübingen40, Siberian State Medical University41, Tomsk State University42, Mental Health Research Institute43
TL;DR: In this article, the authors present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD.
Abstract: The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.
TL;DR: In this Review,luorescence nanoscopy uniquely combines minimally invasive optical access to the internal nanoscale structure and dynamics of cells and tissues with molecular detection specificity and the labelling of individual molecules to enable their visualization has emerged as a central challenge.
Abstract: Fluorescence nanoscopy uniquely combines minimally invasive optical access to the internal nanoscale structure and dynamics of cells and tissues with molecular detection specificity. While the basic physical principles of 'super-resolution' imaging were discovered in the 1990s, with initial experimental demonstrations following in 2000, the broad application of super-resolution imaging to address cell-biological questions has only more recently emerged. Nanoscopy approaches have begun to facilitate discoveries in cell biology and to add new knowledge. One current direction for method improvement is the ambition to quantitatively account for each molecule under investigation and assess true molecular colocalization patterns via multi-colour analyses. In pursuing this goal, the labelling of individual molecules to enable their visualization has emerged as a central challenge. Extending nanoscale imaging into (sliced) tissue and whole-animal contexts is a further goal. In this Review we describe the successes to date and discuss current obstacles and possibilities for further development.
University of Göttingen1, City College of New York2, University of São Paulo3, University of Toronto4, University of Erlangen-Nuremberg5, Aalborg University6, Greifswald University Hospital7, Spaulding Rehabilitation Hospital8, Medical University of South Carolina9, University of Pennsylvania10, Technische Universität Ilmenau11, University of Oldenburg12, École Polytechnique Fédérale de Lausanne13, Paris 12 Val de Marne University14, University of New South Wales15, University of Aberdeen16, University of Trento17, University of Lisbon18, University of Kiel19, Ruhr University Bochum20, Technical University of Dortmund21, Ludwig Maximilian University of Munich22, Beth Israel Deaconess Medical Center23, Mannheim University of Applied Sciences24, University of Siena25, The Catholic University of America26, University College London27, University of Copenhagen28, Fukushima Medical University29, Massachusetts Institute of Technology30, University of Tübingen31
TL;DR: Structured interviews are provided and recommend their use in future controlled studies, in particular when trying to extend the parameters applied, to discuss recent regulatory issues, reporting practices and ethical issues.
Institute of Cancer Research1, Stanford University2, University Hospital of Wales3, Children's Hospital of Philadelphia4, Swiss Institute of Bioinformatics5, The Royal Marsden NHS Foundation Trust6, St George's Hospital7, King's College8, The Chinese University of Hong Kong9, Shandong University10, Boston Children's Hospital11, University of Queensland12, Federal University of São Paulo13, University of Minho14, Beaumont Hospital15, Temple University16, Institut Gustave Roussy17, McGill University18, St. Jude Children's Research Hospital19, University Hospital Heidelberg20, German Cancer Research Center21, Cincinnati Children's Hospital Medical Center22, University of Geneva23, University of Göttingen24
TL;DR: Genomic aberrations increase with age, highlighting the infant population as biologically and clinically distinct, and co-segregating mutations in histone-mutant subgroups including loss of FBXW7 in H 3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H2.1K 27M are identified.
Bielefeld University1, BRICS2, University of Düsseldorf3, Oregon State University4, University of California, San Diego5, Aarhus University6, Roskilde University7, University of Copenhagen8, Joint Genome Institute9, Pittsburgh Supercomputing Center10, Saint Petersburg State University11, Max Planck Society12, University of Vienna13, University of Technology, Sydney14, Centre national de la recherche scientifique15, Genome Institute of Singapore16, University of Warwick17, University of Tübingen18, Intel19, French Institute for Research in Computer Science and Automation20, Taipei Medical University21, Joint BioEnergy Institute22, Lawrence Berkeley National Laboratory23, Georgia Institute of Technology24, University of Calgary25, University of Göttingen26, National Health Research Institutes27, San Diego State University28, Boyce Thompson Institute for Plant Research29, Coordenadoria de Aperfeiçoamento de Pessoal de Nível Superior30, Robert Koch Institute31, University of Maryland, College Park32, Newcastle University33, Leibniz Association34, ETH Zurich35
TL;DR: The Critical Assessment of Metagenome Interpretation (CAMI) challenge has engaged the global developer community to benchmark their programs on highly complex and realistic data sets, generated from ∼700 newly sequenced microorganisms and ∼600 novel viruses and plasmids and representing common experimental setups as discussed by the authors.
Abstract: Methods for assembly, taxonomic profiling and binning are key to interpreting metagenome data, but a lack of consensus about benchmarking complicates performance assessment. The Critical Assessment of Metagenome Interpretation (CAMI) challenge has engaged the global developer community to benchmark their programs on highly complex and realistic data sets, generated from ∼700 newly sequenced microorganisms and ∼600 novel viruses and plasmids and representing common experimental setups. Assembly and genome binning programs performed well for species represented by individual genomes but were substantially affected by the presence of related strains. Taxonomic profiling and binning programs were proficient at high taxonomic ranks, with a notable performance decrease below family level. Parameter settings markedly affected performance, underscoring their importance for program reproducibility. The CAMI results highlight current challenges but also provide a roadmap for software selection to answer specific research questions.
University of Göttingen1, University of Helsinki2, Athens State University3, European Society of Cardiology4, Academy for Urban School Leadership5, Universidade Nova de Lisboa6, Paris Diderot University7, Karolinska University Hospital8, University of Perugia9, University of Warwick10, University of Ferrara11, National and Kapodistrian University of Athens12
TL;DR: The objectives of the present study were to describe epidemiology and outcomes in ambulatory heart failure patients stratified by left ventricular ejection fraction (LVEF) and to identify predictors for mortality at 1 year in each group.
Abstract: Aims
The objectives of the present study were to describe epidemiology and outcomes in ambulatory heart failure (HF) patients stratified by left ventricular ejection fraction (LVEF) and to identify predictors for mortality at 1 year in each group
Methods and results
The European Society of Cardiology Heart Failure Long-Term Registry is a prospective, observational study collecting epidemiological information and 1-year follow-up data in 9134 HF patients Patients were classified according to baseline LVEF into HF with reduced EF [EF 50% (HFpEF)] In comparison with HFpEF subjects, patients with HFrEF were younger (64 years vs 69 years), more commonly male (78% vs 52%), more likely to have an ischaemic aetiology (49% vs 24%) and left bundle branch block (24% vs 9%), but less likely to have hypertension (56% vs 67%) or atrial fibrillation (18% vs 32%) The HFmrEF group resembled the HFrEF group in some features, including age, gender and ischaemic aetiology, but had less left ventricular and atrial dilation Mortality at 1 year differed significantly between HFrEF and HFpEF (88% vs 63%); HFmrEF patients experienced intermediate rates (76%) Age, New York Heart Association (NYHA) class III/IV status and chronic kidney disease predicted mortality in all LVEF groups Low systolic blood pressure and high heart rate were predictors for mortality in HFrEF and HFmrEF A lower body mass index was independently associated with mortality in HFrEF and HFpEF patients Atrial fibrillation predicted mortality in HFpEF patients
Conclusions
Heart failure patients stratified according to different categories of LVEF represent diverse phenotypes of demography, clinical presentation, aetiology and outcomes at 1 year Differences in predictors for mortality might improve risk stratification and management goals
TL;DR: The authors identify conditions, where the microtubule-binding repeats of Tau undergo a phosphorylation-dependent liquid–liquid phase separation, leading to molecular crowding in the formed Tau liquid droplets and characterize them by NMR and other biophysical methods.
Abstract: The protein Tau aggregates into tangles in the brain of patients with Alzheimer's disease. In solution, however, Tau is intrinsically disordered, highly soluble, and binds to microtubules. It is still unclear what initiates the conversion from an innocuous phase of high solubility and functionality to solid-like neurotoxic deposits. Here, we show that the microtubule-binding repeats of Tau, which are lysine-rich, undergo liquid-liquid phase separation in solution. Liquid-liquid demixing causes molecular crowding of amyloid-promoting elements of Tau and drives electrostatic coacervation. Furthermore, we demonstrate that three-repeat and four-repeat isoforms of Tau differ in their ability for demixing. Alternative splicing of Tau can thus regulate the formation of Tau-containing membrane-less compartments. In addition, phosphorylation of Tau repeats promotes liquid-liquid phase separation at cellular protein conditions. The combined data propose a mechanism in which liquid droplets formed by the positively charged microtubule-binding domain of Tau undergo coacervation with negatively charged molecules to promote amyloid formation.Tau forms aggregates in the brains of Alzheimer patients. Here, the authors identify conditions, where the microtubule-binding repeats of Tau undergo a phosphorylation-dependent liquid-liquid phase separation, leading to molecular crowding in the formed Tau liquid droplets and characterize them by NMR and other biophysical methods.
TL;DR: The findings suggest that large diabetes-associated costs are not only a problem in high-income settings but also affect poorer world regions, and further research in low-income regions is needed.
TL;DR: This paper presents a short overview of the changes to the trigger and data acquisition systems during the first long shutdown of the LHC and shows the performance of the trigger system and its components based on the 2015 proton–proton collision data.
Abstract: During 2015 the ATLAS experiment recorded 3.8 fb(-1) of proton-proton collision data at a centre-of-mass energy of 13 TeV. The ATLAS trigger system is a crucial component of the experiment, respons ...
TL;DR: The methodology of an important class of ML potentials that employs artificial neural networks is considered, which can accelerate computer simulations by several orders of magnitude, while preserving quantum mechanical accuracy.
Abstract: Modern simulation techniques have reached a level of maturity which allows a wide range of problems in chemistry and materials science to be addressed. Unfortunately, the application of first principles methods with predictive power is still limited to rather small systems, and despite the rapid evolution of computer hardware no fundamental change in this situation can be expected. Consequently, the development of more efficient but equally reliable atomistic potentials to reach an atomic level understanding of complex systems has received considerable attention in recent years. A promising new development has been the introduction of machine learning (ML) methods to describe the atomic interactions. Once trained with electronic structure data, ML potentials can accelerate computer simulations by several orders of magnitude, while preserving quantum mechanical accuracy. This Review considers the methodology of an important class of ML potentials that employs artificial neural networks.
TL;DR: Spectral interferometry images the formation, binding, and internal dynamics of optical soliton complexes as they propagated in a laser cavity and tracks two- and three-soliton bound states over hundreds of thousands of consecutive cavity roundtrips, implying that its dynamics may be topologically protected.
Abstract: Solitons, particle-like excitations ubiquitous in many fields of physics, have been shown to exhibit bound states akin to molecules. The formation of such temporal soliton bound states and their internal dynamics have escaped direct experimental observation. By means of an emerging time-stretch technique, we resolve the evolution of femtosecond soliton molecules in the cavity of a few-cycle mode-locked laser. We track two- and three-soliton bound states over hundreds of thousands of consecutive cavity roundtrips, identifying fixed points and periodic and aperiodic molecular orbits. A class of trajectories acquires a path-dependent geometrical phase, implying that its dynamics may be topologically protected. These findings highlight the importance of real-time detection in resolving interactions in complex nonlinear systems, including the dynamics of soliton bound states, breathers, and rogue waves.
TL;DR: In this article, insights into the mechanisms of mitochondrial dysfunction in heart failure are presented, along with an overview of emerging treatments with the potential to improve the function of the failing heart by targeting mitochondria.
Abstract: Heart failure is a pressing worldwide public-health problem with millions of patients having worsening heart failure. Despite all the available therapies, the condition carries a very poor prognosis. Existing therapies provide symptomatic and clinical benefit, but do not fully address molecular abnormalities that occur in cardiomyocytes. This shortcoming is particularly important given that most patients with heart failure have viable dysfunctional myocardium, in which an improvement or normalization of function might be possible. Although the pathophysiology of heart failure is complex, mitochondrial dysfunction seems to be an important target for therapy to improve cardiac function directly. Mitochondrial abnormalities include impaired mitochondrial electron transport chain activity, increased formation of reactive oxygen species, shifted metabolic substrate utilization, aberrant mitochondrial dynamics, and altered ion homeostasis. In this Consensus Statement, insights into the mechanisms of mitochondrial dysfunction in heart failure are presented, along with an overview of emerging treatments with the potential to improve the function of the failing heart by targeting mitochondria.
TL;DR: A rapid search in PubMed shows that using "flow cytometry immunology" as a search term yields more than 68 000 articles, the first of which is not about lymphocytes as mentioned in this paper.
Abstract: The marriage between immunology and cytometry is one of the most stable and productive in the recent history of science. A rapid search in PubMed shows that, as of July 2017, using “flow cytometry immunology” as a search term yields more than 68 000 articles, the first of which, interestingly, is not about lymphocytes. It might be stated that, after a short engagement, the exchange of the wedding rings between immunology and cytometry officially occurred when the idea to link fluorochromes to monoclonal antibodies came about. After this, recognizing different types of cells became relatively easy and feasible not only by using a simple fluorescence microscope, but also by a complex and sometimes esoteric instrument, the flow cytometer that is able to count hundreds of cells in a single second, and can provide repetitive results in a tireless manner. Given this, the possibility to analyse immune phenotypes in a variety of clinical conditions has changed the use of the flow cytometer, which was incidentally invented in the late 1960s to measure cellular DNA by using intercalating dyes, such as ethidium bromide. The epidemics of HIV/AIDS in the 1980s then gave a dramatic impulse to the technology of counting specific cells, since it became clear that the quantification of the number of peripheral blood CD4+ T cells was crucial to follow the course of the infection, and eventually for monitoring the therapy. As a consequence, the development of flow cytometers that had to be easy-to-use in all clinical laboratories helped to widely disseminate this technology. Nowadays, it is rare to find an immunological paper or read a conference abstract in which the authors did not use flow cytometry as the main tool to dissect the immune system and identify its fine and complex functions. Of note, recent developments have created the sophisticated technology of mass cytometry, which is able to simultaneously identify dozens of molecules at the single cell level and allows us to better understand the complexity and beauty of the immune system.
TL;DR: The emergence of transient directing group approaches through the in situ installation and deconstruction of a Lewis-basic entity with the aid of co-catalytic additives for selective C–H functionalizations is discussed.
TL;DR: Changes in the rRNA modification pattern have been observed in response to environmental changes, during development, and in disease, which suggests that rRNA modifications may contribute to the translational control of gene expression.
Abstract: rRNAs are extensively modified during their transcription and subsequent maturation in the nucleolus, nucleus and cytoplasm. RNA modifications, which are installed either by snoRNA-guided or by stand-alone enzymes, generally stabilize the structure of the ribosome. However, they also cluster at functionally important sites of the ribosome, such as the peptidyltransferase center and the decoding site, where they facilitate efficient and accurate protein synthesis. The recent identification of sites of substoichiometric 2'-O-methylation and pseudouridylation has overturned the notion that all rRNA modifications are constitutively present on ribosomes, highlighting nucleotide modifications as an important source of ribosomal heterogeneity. While the mechanisms regulating partial modification and the functions of specialized ribosomes are largely unknown, changes in the rRNA modification pattern have been observed in response to environmental changes, during development, and in disease. This suggests that rRNA modifications may contribute to the translational control of gene expression.
TL;DR: Topological cell clustering is established as a well-performing calorimeter signal definition for jet and missing transverse momentum reconstruction in ATLAS and is exploited to apply a local energy calibration and corrections depending on the nature of the cluster.
Abstract: The reconstruction of the signal from hadrons and jets emerging from the proton–proton collisions at the Large Hadron Collider (LHC) and entering the ATLAS calorimeters is based on a three-dimensional topological clustering of individual calorimeter cell signals. The cluster formation follows cell signal-significance patterns generated by electromagnetic and hadronic showers. In this, the clustering algorithm implicitly performs a topological noise suppression by removing cells with insignificant signals which are not in close proximity to cells with significant signals. The resulting topological cell clusters have shape and location information, which is exploited to apply a local energy calibration and corrections depending on the nature of the cluster. Topological cell clustering is established as a well-performing calorimeter signal definition for jet and missing transverse momentum reconstruction in ATLAS.
University of Sydney1, St George's Hospital2, Johns Hopkins University3, Population Health Research Institute4, Karolinska Institutet5, Ruijin Hospital6, Brigham and Women's Hospital7, The George Institute for Global Health8, Barts Health NHS Trust9, Boston University10, University of Modena and Reggio Emilia11, National Yang-Ming University12, University Hospital of Basel13, François Rabelais University14, University of Birmingham15, Mayo Clinic16, University of Toronto17, University of Western Australia18, Trinity College, Dublin19, Cornell University20, Lankenau Institute for Medical Research21, The Chinese University of Hong Kong22, Aalborg University23, Edinburgh Napier University24, Duke University25, University of Auckland26, University of Belgrade27, University of Groningen28, University of Alberta29, University of Hong Kong30, University of Copenhagen31, Stanford University32, VA Palo Alto Healthcare System33, University of Göttingen34
TL;DR: A strong case for AF screening now is provided while recognizing that large randomized outcomes studies would be helpful to strengthen the evidence base.
Abstract: Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed in September 2015 to promote discussion and research about AF screening as a strategy to reduce stroke and death and to provide advocacy for implementation of country-specific AF screening programs. During 2016, 60 expert members of AF-SCREEN, including physicians, nurses, allied health professionals, health economists, and patient advocates, were invited to prepare sections of a draft document. In August 2016, 51 members met in Rome to discuss the draft document and consider the key points arising from it using a Delphi process. These key points emphasize that screen-detected AF found at a single timepoint or by intermittent ECG recordings over 2 weeks is not a benign condition and, with additional stroke factors, carries sufficient risk of stroke to justify consideration of anticoagulation. With regard to the methods of mass screening, handheld ECG devices have the advantage of providing a verifiable ECG trace that guidelines require for AF diagnosis and would therefore be preferred as screening tools. Certain patient groups, such as those with recent embolic stroke of uncertain source (ESUS), require more intensive monitoring for AF. Settings for screening include various venues in both the community and the clinic, but they must be linked to a pathway for appropriate diagnosis and management for screening to be effective. It is recognized that health resources vary widely between countries and health systems, so the setting for AF screening should be both country- and health system-specific. Based on current knowledge, this white paper provides a strong case for AF screening now while recognizing that large randomized outcomes studies would be helpful to strengthen the evidence base.
TL;DR: A proof-of-concept for a universally applicable technology for the engineering of macroscale human myocardium for disease modeling and heart repair from embryonic and induced pluripotent stem cell–derived cardiomyocytes under defined, serum-free conditions is provided.
Abstract: Background:Advancing structural and functional maturation of stem cell–derived cardiomyocytes remains a key challenge for applications in disease modeling, drug screening, and heart repair. Here, w...
TL;DR: The trial shows that early de-escalation of antiplatelet treatment can be considered as an alternative approach in patients with acute coronary syndrome managed with PCI and was non-inferior to standard treatment with prasugrel at 1 year after PCI.
TL;DR: In this paper, microfluidic devices that allow the culture of cell populations in different compartments were used to investigate the spreading of tau pathology, and they showed that exosomes mediate trans-neuronal transfer of Tau depending on synaptic connectivity.
Abstract: Tau pathology in AD spreads in a hierarchical pattern, whereby it first appears in the entorhinal cortex, then spreads to the hippocampus and later to the surrounding areas. Based on this sequential appearance, AD can be classified into six stages (“Braak stages”). The mechanisms and agents underlying the progression of Tau pathology are a matter of debate. Emerging evidence indicates that the propagation of Tau pathology may be due to the transmission of Tau protein, but the underlying pathways and Tau species are not well understood. In this study we investigated the question of Tau spreading via small extracellular vesicles called exosomes. Exosomes from different sources were analyzed by biochemical methods and electron microscopy (EM) and cryo-EM. Microfluidic devices that allow the culture of cell populations in different compartments were used to investigate the spreading of Tau. We show that Tau protein is released by cultured primary neurons or by N2a cells overexpressing different Tau constructs via exosomes. Neuron-derived exosomal Tau is hypo-phosphorylated, compared with cytosolic Tau. Depolarization of neurons promotes release of Tau-containing exosomes, highlighting the importance of neuronal activity. Using microfluidic devices we show that exosomes mediate trans-neuronal transfer of Tau depending on synaptic connectivity. Tau spreading is achieved by direct transmission of exosomes between neurons. In organotypic hippocampal slices, Tau-containing exosomes in conditioned medium are taken up by neurons and microglia, not astrocytes. In N2a cells, Tau assemblies are released via exosomes. They can induce inclusions of other Tau molecules in N2a cells expressing mutant human Tau. We also studied exosomes from cerebrospinal fluid in AD and control subjects containing monomeric and oligomeric Tau. Split-luciferase complementation reveals that exosomes from CSF can promote Tau aggregation in cultured cells. Our study demonstrates that exosomes contribute to trans-synaptic Tau transmission, and thus offer new approches to control the spreading of pathology in AD and other tauopathies.