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  • 1
    Publication Date: 2020-10-16
    Description: Reliable automatic procedure for locating earthquake in quasi-real time is strongly needed for seismic warning system, earthquake preparedness, and producing shaking maps. The reliability of an automatic location algorithm is influenced by several factors such as errors in picking seismic phases, network geometry, and velocity model uncertainties. The main purpose of this work is to investigate the performances of different automatic procedures to choose the most suitable one to be applied for the quasi-real-time earthquake locations in northwestern Italy. The reliability of two automatic-picking algorithms (one based on the Characteristic Function (CF) analysis, CF picker, and the other one based on the Akaike Information Criterion (AIC), AIC picker) and two location methods (“Hypoellipse” and “NonLinLoc” codes) is analysed by comparing the automatically determined hypocentral coordinates with reference ones. Reference locations are computed by the “Hypoellipse” code considering manually revised data and tested using quarry blasts. The comparison is made on a dataset composed by 575 seismic events for the period 2000–2007 as recorded by the Regional Seismic network of Northwestern Italy. For P phases, similar results, in terms of both amount of detected picks and magnitude of travel time differences with respect to manual picks, are obtained applying the AIC and the CF picker; on the contrary, for S phases, the AIC picker seems to provide a significant greater number of readings than the CF picker. Furthermore, the “NonLin- Loc” software (applied to a 3D velocity model) is proved to be more reliable than the “Hypoellipse” code (applied to layered 1D velocity models), leading to more reliable automatic locations also when outliers (wrong picks) are present.
    Description: Published
    Description: 393–411
    Description: 8T. Sismologia in tempo reale
    Description: JCR Journal
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 2
    Publication Date: 2020-11-12
    Description: Public concern about anthropogenic seismic- ity in Italy first arose in the aftermath of the deadly M ≈ 6 earthquakes that hit the Emilia-Romagna region (northern Italy) in May 2012. As these events occurred in a (tectonically active) region of oil and gas production and storage, the question was raised, whether stress perturbations due to underground industrial activities could have induced or triggered the shocks. Following expert recommendations, in 2014, the Italian Oil & Gas Safety Authority (DGS-UNMIG, Ministry of Economic Development) published guidelines (ILG - Indirizzi e linee guida per il monitoraggio della sismicità, delle deformazioni del suolo e delle pressioni di poro nell’ambito delle attività antropiche), describing regula- tions regarding hydrocarbon extraction, waste-water in- jection and gas storage that could also be adapted to other technologies, such as dams, geothermal systems, CO2 storage, and mining. The ILG describe the frame- work for the different actors involved in monitoring activities, their relationship and responsibilities, the procedure to be followed in case of variations of mon- itored parameters, the need for in-depth scientific anal- yses, the definition of different alert levels, their mean- ing and the parameters to be used to activate such alerts. Four alert levels are defined, the transition among which follows a decision to be taken jointly by relevant au- thorities and industrial operator on the basis of evalua- tion of several monitored parameters (micro-seismicity, ground deformation, pore pressure) carried on by a scientific-technical agency. Only in the case of liquid reinjection, the alert levels are automatically activated on the basis of exceedance of thresholds for earthquake magnitude and ground shaking – in what is generally known as a Traffic Light System (TLS). Istituto Nazionale di Geofisica e Vulcanologia has been charged by the Italian oil and gas safety authority (DGS- UNMIG) to apply the ILG in three test cases (two oil extraction and one gas storage plants). The ILG indeed represent a very important and positive innovation, as they constitute official guidelines to coherently regulate monitoring activity on a national scale. While pilot studies are still mostly under way, we may point out merits of the whole framework, and a few possible critical issues, requiring special care in the implementa- tion. Attention areas of adjacent reservoirs, possibly licenced to different operators, may overlap, hence mak- ing the point for joint monitoring, also in view of the possible interaction between stress changes related to the different reservoirs. The prescribed initial blank- level monitoring stage, aimed at assessing background seismicity, may lose significance in case of nearby ac- tive production. Magnitude – a critical parameter used to define a possible step-up in activation levels – has inherent uncertainty and can be evaluated using differ- ent scales. A final comment considers the fact that relevance of TLS, most frequently used in hydraulic fracturing operations, may not be high in case of trig- gered tectonic events.
    Description: Published
    Description: 1015–1028
    Description: 1IT. Reti di monitoraggio e sorveglianza
    Description: JCR Journal
    Keywords: Anthropogenic seismicity ; Alert system ; Monitoring guidelines ; 04.06. Seismology ; 05.04. Instrumentation and techniques of general interest
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: article
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  • 3
    Publication Date: 2020-11-09
    Description: This work presents the first chemical and isotopic (δ13C-CO2, δ13C-CH4, 3He, 4He, 20Ne, 40Ar, 36Ar, δ18O, and δD) data for fluid discharges fromGuallatiri volcano, a remote and massive stratovolcano, which is considered as the second most active volcano of the Central Volcanic Zone (CVZ) in northern Chile. Fumarolic gases had outlet temperatures of between 80.2 and 265 °C, and showed a significant magmatic fluid contribution marked by the occurrence of SO2, HCl, and HF that are partially scrubbed by a hydrothermal aquifer. The helium isotope ratios (〈 3.2) were relatively low compared to those of other active volcanoes in CVZ, possibly due to contamination of the magmatic source by 4He-rich crust and/or crustal fluid addition to the hydrothermal reservoir. Geothermometry in the H2O-CO2-CO-H2-CH4 system suggests equilibrium temperatures of up to 320 °C attained in a vapor phase at redox conditions intermediate between those typical of hydrothermal and magmatic environments. Thermal springs located 12 km northwest of the volcano’s summit had outlet temperatures of up to 50.1 °C, neutral to slightly basic pH, and a sodium bicarbonate composition, typical of distal fluid discharges in volcanic systems. Cold springs at the base of the volcanic edifice, showing a calcium sulfate composition, were likely produced by interaction of shallow meteoric water with CO2- andH2S-rich gases. A geochemical conceptual model was constructed to graphically represent these results, which can be used as an indication for future geochemical monitoring and volcanic hazard assessment.
    Description: Published
    Description: id 57
    Description: 2V. Struttura e sistema di alimentazione dei vulcani
    Description: 4V. Processi pre-eruttivi
    Description: JCR Journal
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 4
    Publication Date: 2020-12-18
    Description: In this paper, we present results of the reconstruction of the total grain size distribution (TGSD) of the material erupted during explosive volcanic eruptions at Campi Flegrei (Italy) considering all components (juvenile, lithic and crystal clasts). To date, the few TGSDs made available have been mostly reconstructed by assuming that the tephra deposits consisted of only one component. This simplification can introduce substantial bias in the interpretation of magma fragmentation mechanisms and significantly affect ash dispersion forecasts, since each tephra component has specific aerodynamic characteristics. By means of field investigations and laboratory analyses on samples collected from deposits of the Agnano-Monte Spina and Astroni eruptions, we reconstructed the TGSDs of juvenile, lithic and crystal components via the Voronoi tessellation method. Our results show how the systematic reconstruction of a TGSD, from the component-specific to the bulk TGSD, can provide important information on magma fragmentation mechanisms and wall-rock erosion processes. Results confirm that the bulk TGSD is the combination of the merging of different component subpopulations, according to their own TGSD, density and relative mass proportions. In addition, the integration of component analysis, TGSD and settling velocity data allowed characterization of the aerodynamic behaviour of each component at variable distances from the vent, which can be related to their own parent grain size distribution. The integration of new data from distal tephra deposits for the considered eruptions has thus allowed a reassessment of the erupted volumes of eruptions considered in this research, which are now 3.17 and 0.63 km3, for Agnano-Monte Spina and Astroni, respectively.
    Description: Published
    Description: id 31
    Description: 3V. Proprietà chimico-fisiche dei magmi e dei prodotti vulcanici
    Description: JCR Journal
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 5
    Publication Date: 2020-10-01
    Description: Several months of ambient seismic noise recordings are used for investigating the distribution of elastic properties in the Fucino Plain, one of the largest intermontane tectonic depressions of the Italian Apennine chain (Central Italy). The Plain is characterized by a low level of seismicity but the presence of several active faults makes it an Italian area of high seismic hazard. The most recent and strongest seismic event in Fucino Plain occurred in the 1915 (Avezzano earthquake) and it represents one of the most energetic events (Ms = 7.0) happened in central Apennines. Inter-stations Green’s functions are reconstructed by the cross-correlation of continuous ambient noise data recorded from twelve seismic velocimeters deployed around the Avezzano city, and organized in two different temporally sub-networks. The aim of cross-correlation analysis is to extract surface waves from Green’s functions for investigating the dispersive response of the structure. We analyzed the temporal stability of the cross-correlated signals that is used as an indicator of reliability of measurements and as criteria to select the Green’s functions to analyze
    Description: Published
    Description: 1173-1176
    Description: 5T. Sismologia, geofisica e geologia per l'ingegneria sismica
    Keywords: Cross correlation ; Noise ; 04.06. Seismology
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: book chapter
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  • 6
    Publication Date: 2020-10-20
    Description: Pyrite and organic matter closely coexist in some hydrothermally-altered gabbroic xenoliths from the Hyblean Plateau, Sicily. The representative sample consists of plagioclase, Fe-oxides, clinopyroxene, pyrite and minor amounts of many other minerals. Plagioclase displays incipient albitization, clinopyroxene is deeply corroded. Pyrite grains are widely replaced by spongy-textured magnetite, which locally hosts Ca-(and Fe-)sulfate micrograins and blebs of condensed organic matter. Whole-rock trace element distribution evidences that incompatible elements, particularly the fluid-mobile Ba, U and Pb, are significantly enriched with respect to N-MORB values. The mineralogical and geochemical characteristics of the sample, and its U-Pb zircon age of 216.9 ± 6.7 MA, conform to the xenolith-based viewpoint that the unexposed Hyblean basement is a relict of the Ionian Tethys lithospheric domain, mostly consisting of abyssal-type serpentinized peridotites with small gabbroic intrusions. Circulating hydrothermal fluids there favored the formation of hydrocarbons trough Fischer-Tropsch-type organic synthesis, giving also rise to sulfidization episodes. Subsequent variations in temperature and redox conditions of the system induced partial de-sulfidization, Fe-oxides precipitation and sulfate-forming reactions, also promoting poly-condensation and aromatization of the already-formed hydrocarbons. Here we show organic matter adhering to a crystal face of a microscopic pyrite grain. Pyrite surfaces, as abiotic analogues of enzymes, can adsorb and concentrate organic molecules, also acting as catalysts for a broad range of proto-biochemical reactions. The present data therefore may support established abiogenesis models suggesting that pyrite surfaces carried out primitive metabolic cycles in suitable environments of the early Earth, such as endolithic recesses in mafic rocks permeated by hydrothermal fluids.
    Description: Published
    Description: 19-47
    Description: 4V. Processi pre-eruttivi
    Description: JCR Journal
    Keywords: Abiogenesis ; FTT synthesis ; Hydrothermal system ; Pyrite ; Sicily ; Xenoliths
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 7
    Publication Date: 2020-10-22
    Description: The earthquake occured in Tohoku (Japan) in 2011 showed that no matter how outstanding is the model of the mitigation of natural hazard, an earthquake can always surprise any studied attempt to contain a tsunami. I report this extreme example to draw the reader attention on how strong should be the commitment of the society in producing the optimal conditions to face natural hazard. Every country has a peculiar social context. If in the past we considered this as a secondary aspect, now we are obliged to recognize that the social context is of main importance when promoting mitigation of natural hazard. In this occasion I would like to refer to my experience as an educator in my country. Italy is a country where it is difficult to promote a dialogue between the Institutions and the citizens. The dialogue is difficult also among the communities of engineers, geologists and politicians. There is still a great confusion on the attribution of tasks and a lot of problems of difficult solution are related to corruption. In this context, education can play a crucial role and should be intensively addressed to promote geo-awareness in the citizens. People should learn about the geological site where their houses are built and get all the info necessary to understand if it has been done according to the law. Only in this way citizens become an active agent in promoting those changes without which an efficacious mitigation of natural hazard is impossible.
    Description: Published
    Description: 85-88
    Description: 3TM. Comunicazione
    Keywords: Risk communication, Earth Education, Public Awareness ; 05.03. Educational, History of Science, Public Issues
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: book chapter
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  • 8
    Publication Date: 2020-11-30
    Description: Buildings close to each other can perform different behaviour despite its similar seismic vulnerability. This effect is mainly due to the local seismic response connected to the characteristics of the shallow soil layers, especially when we move away from the epicentral area and the near field motion reduces its importance among the total amount of shaking. In this paper we show some results of the microzonation project of the Avezzano municipality, a town located in the southwestern portion of the Abruzzi region, which experienced the severe effects of the January 13th, 1915 M 7.0 earthquake. Starting from a particularly detailed knowledge of the geological characteristics of outcropping lithologies and inferring the trend of subsoil geometries, we explored the role played by the near-surface geology in causing variability of the ground motion by analysing a large database of earthquakes and microtremor recordings acquired by temporary seismological networks using classical site-reference and non-reference spectral techniques. Based on the obtained results we can seismically characterize all the municipal territory not only in terms of fundamental resonance frequency, useful in drawing maps of seismic microzonation and design geological sections, but also of amplification factors helpful in verifying numerical modelling of seismic response as required by national microzonation guidelines. We have also found many criticisms that need a more detailed analysis in order to establish the cause of these anomalies.
    Description: Published
    Description: 1153-1157
    Description: 5T. Sismologia, geofisica e geologia per l'ingegneria sismica
    Keywords: Microzonation ; Site response ; Spectral techniques ; Seismic amplification ; 04.06. Seismology
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: book chapter
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  • 9
    Publication Date: 2020-12-15
    Description: Sub-surface operations for energy production such as gas storage, fluid reinjection or hydraulic fracking may modify the physical properties of the rocks, in particular the seismic velocity and the anelastic attenuation. The aim of the present study is to investigate, through a synthetic test, the possibility of using empirical ground-motion prediction equations (GMPEs) to observe the variations in the reservoir. In the synthetic test, we reproduce the expected seismic activity (in terms of rate, focal mechanisms, stress drop and the b value of the Gutenberg-Richter) and the variation of medium properties in terms of the quality factor Q induced by a fluid injection experiment. In practice, peak-ground velocity data of the simulated earthquakes during the field operations are used to update the coefficients of a reference GMPE in order to test whether the coefficients are able to capture the medium properties variation. The results of the test show that the coefficients of the GMPE vary during the simulated field operations revealing their sensitivity to the variation of the anelastic attenuation. The proposed approach is suggested as a promising tool that, if confirmed by real data analysis, could be used for monitoring and interpreting induced seismicity in addition to more conventional techniques.
    Description: for Clean Energy) project, which received funding from the European Union’s Horizon 2020 research and innovation action, under grant agreement No 764810, and was partially funded by the PRIN Project MATISSE (Bando 2017, Prot. 20177EPPN2).
    Description: Published
    Description: 723–735
    Description: 5T. Sismologia, geofisica e geologia per l'ingegneria sismica
    Description: JCR Journal
    Keywords: Induced seismicity ; Anelastic attenuation ; Ground motion predictive equations
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 10
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    Springer
    Publication Date: 2020-11-25
    Description: Relative and absolute gravimetric measurements are carried out for metrological, geodetic and geophysical (structural and dynamic) studies. Gravimetry is largely used in Italy since long time for vast set of studies. Both relative and absolute measurements are carried out in several fields of geodesy, geophysics and geodynamic with different approaches. After a brief historical excursus, the paper presents the State of the Art of “Modern” Gravimetry in Italy in its various applications, together the main available results and products, with particular attention to: - Development of modern gravimetry in Italy: from relative to absolute measurements. - Italian Reference Gravity Networks: state of the art - The Italian gravimetric map: its evolution over time, data, the present-day status and related products. - Dynamic gravimetry: examples of applications in geodynamical areas. Finally, suggestions for future perspectives for gravimetry in Italy are outlined.
    Description: Published
    Description: 35–48
    Description: 1IT. Reti di monitoraggio e sorveglianza
    Description: JCR Journal
    Keywords: Gravimetria ; Reti di riferimento e monitoraggio
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 11
    Publication Date: 2020-11-30
    Description: This work aimed to study geochemical data, composed of major and trace elements describing volcanic rocks collected from the Campanian active volcanoes of Vesuvius, Campi Flegrei and Ischia Island. The data were analyzed through the Self-Organizing Map (SOM) unsupervised neural net. SOM is able to group the input data into clusters according to their intrinsic similarities without using any information derived from previous geochemical-petrological considerations. The net was trained on a dataset of 276 geochemical patterns of which 96 belonged to Ischia, 94 to Vesuvius and 86 to Campi Flegrei volcanoes. Two investigations were carried out. The first one aimed to cluster geochemical data mainly characterizing the type of volcanic rocks of the three volcanic areas. The SOM clustering well grouped the oldest volcanic products of Ischia, Vesuvius and Campi Flegrei identifying a similar behaviour for the rocks emplaced in the oldest activity periods (〉19 ka), and showing their different evolution over time. In the second test, devoted to inferring information on the magmatic source, the ratios of significant trace elements and K2O/Na2O have been used as input data. The SOM results highlighted a high degree of affinity between the geochemical element ratios of Vesuvius and Campi Flegrei that were separated from the products of Ischia. This result was also evidenced through isotope ratios by using traditional two-dimensional diagrams.
    Description: Published
    Description: 175-184
    Description: 2V. Struttura e sistema di alimentazione dei vulcani
    Description: 3V. Proprietà chimico-fisiche dei magmi e dei prodotti vulcanici
    Description: 4V. Processi pre-eruttivi
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
    Type: book chapter
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  • 12
    Publication Date: 2020-11-25
    Description: Over the past few decades, substantial progress has been made to overcome the technical difficulties of continuously measuring volcanic SO2 emissions. However, measurements of CO2 emissions still present many difficulties, partly due to the lack of instruments that can directly measure CO2 emissions and partly due to its strong atmospheric background. In order to overcome these difficulties, a commonly taken approach is to combine differential optical absorption spectroscopy (DOAS) by using NOVAC scan-DOAS instruments for continuous measurements of crateric SO2 emissions, and electrochemical/NDIR multi-component gas analyser system (multi-GAS) instruments for measuring CO2/SO2 ratios of excerpts of the volcanic plume. This study aims to quantify the representativeness of excerpts of CO2/SO2 ratios measured by Multi-GAS as a fraction of the whole plume composition, by comparison with simultaneously measured CO2/SO2 ratios using cross-crater Fourier transform infrared spectroscopy (FTIR). Two study cases are presented: Telica volcano (Nicaragua), with a homogenous plume, quiescent degassing from a deep source and ambient temperature, and Turrialba volcano (Costa Rica), which has a non-homogeneous plume from three main sources with different compositions and temperatures. Our comparison shows that in our “easier case” (Telica), FTIR and Multi-GAS CO2/SO2 ratios agree within a factor about 3 %. In our “complicated case” (Turrialba), Multi-GAS and FTIR yield CO2/SO2 ratios differing by approximately 13–25 % at most. These results suggest that a fair estimation of volcanic CO2 emissions can be provided by the combination of DOAS and Multi-GAS instruments for volcanoes with similar degassing conditions as Telica or Turrialba. Based on the results of this comparison, we report that by the time our measurements were made, Telica and Turrialba were emitting approximately 100 and 1,000 t day−1 of CO2, respectively.
    Description: This work was supported by the Swedish International Development Agency (SIDA), and the DECADE initiative in coordination with OVSICORI-UNA and INETER. The research leading to these results received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007/2013)/ERC grant agreement n1305377 (PI Aiuppa)
    Description: Published
    Description: 2335–2347
    Description: 4V. Processi pre-eruttivi
    Description: JCR Journal
    Keywords: volcanic degassing ; Multi-GAS ; UV spectroscopy ; FTIR
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 13
    Publication Date: 2020-12-14
    Description: Thrusting at shallow depths often precludes analysis by means of structural indicators effective in other geological contexts (e.g., mylonites, sheath folds, shear bands). In this paper, a combination of techniques (includ- ing structural analysis, magnetic methods, as anisotropy of magnetic susceptibility and paleomagnetism, and paleo- thermometry) is used to define thrusting conditions, defor- mation, and transport directions in the Cameros–Demanda thrust (North Spain). Three outcrops were analyzed along this intraplate, large-scale major structure having 150 km of outcropping length, 30 km of maximum horizontal dis- placement, and 5 km of vertical throw. Results obtained by means of the different techniques are compared with data derived from cross sections and stratigraphic analy- sis. Mixed-layer illite–smectite and vitrinite reflectance indicating deep diagenetic conditions and mature stage of hydrocarbon generation suggests shallow depths during deformation, thus confirming that the protolith for most of the fault rocks is the footwall of the main thrust. Kinematic indicators (foliation, S/C structures, and slickenside stria- tions) indicate altogether a dominant NNW movement of the hanging wall in the western zone and NE in the eastern zone of the thrust, thus implying strain partitioning between different branches of the main thrust. The study of AMS in fault rocks (nearly 400 samples of fault gouge, breccia, and microbreccia) indicates that the strike of magnetic foliation is oblique to the transport direction and that the magnetic lineation parallelizes the projection of the transport direc- tion onto the kmax/kint plane in sites with strong shear defor- mation. Paleomagnetism applied to fault rocks indicates the existence of remagnetizations linked to thrusting, in spite of the shallow depth for deformation, and a strong defor- mation or scattering of the magnetic remanence vectors in the fault zone. The application of the described techniques and consistency of results indicate that the proposed multi- disciplinary approach is useful when dealing with thrusts at shallow crustal levels.
    Description: Published
    Description: 1023–1055
    Description: 1A. Geomagnetismo e Paleomagnetismo
    Description: JCR Journal
    Keywords: Intraplate thrusting ; Fault rock ; Cameros–Demanda thrust ; Transport direction ; Magnetic techniques ; Paleothermometry ; Solid Earth
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 14
    Publication Date: 2020-12-15
    Description: The occurrence time of earthquakes can be anticipated or delayed by external phenomena that induce strain energy changes on the faults. ‘Anticipated’ earthquakes are generally called ‘triggered’; however, it can be controversial to label a specific earthquake as such, mostly because of the stochastic nature of earthquake occurrence and of the large uncertainties usually associated to stress modelling. Here we introduce a combined statistical and physical approach to quantify the probability that a given earthquake was triggered by a given stress-inducing phenomenon. As an example, we consider an earthquake that was likely triggered by a natural event: the M = 6.2 13 Jan 1976 Kópasker earthquake on the Grímsey lineament (Tjörnes Fracture Zone, Iceland), which occurred about 3 weeks after a large dike injection in the nearby Krafla fissure swarm. By using Coulomb stress calculations and the rate-and-state earthquake nucleation theory, we calculate the likelihood of the earthquake in a scenario that contains only the tectonic background and excludes the dike and in a scenario that includes the dike but excludes the background. Applying the Bayes’ theorem, we obtain that the probability that the earthquake was indeed triggered by the dike, rather than purely due to the accumulation of tectonic strain, is about 60 to 90 %. This methodology allows us to assign quantitative probabilities to different scenarios and can help in classifying earthquakes as triggered or not triggered by natural or human-induced changes of stress in the crust.
    Description: Published
    Description: 165–187
    Description: 5T. Sismologia, geofisica e geologia per l'ingegneria sismica
    Description: JCR Journal
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  • 15
    Publication Date: 2021-01-20
    Description: Zircon from syenitic ejecta of Vesuvius (Campania, Italy) is unusually blue, a property shared with gem zircon from Ratanakiri province (Cambodia), which turns from natural reddish-brown to blue when heated under reducing conditions. Here, the origins of these unusual crystals were traced through geochronology, trace elements, and O-Hf isotopic compositions. The causes of its colour were investigated through optical and electron microscopy, optical absorption spectroscopy, and Raman microspectroscopy. Colour stability upon heating and ultraviolet light (UV) exposure was tested using Ratanakiri zircon as a control. Vesuvius zircon contains vesiculated zones with abundant inclusions ~2.5 μm to 〈100 nm in diameter (mostly U-rich thorianite and pyrochlore-group minerals), while homogeneous zircon domains are high in Th and U (up to 5.9 and 1.8 wt%, respectively). Its blue colouration is stable under UV radiation, as well as heat-treatment under reducing conditions (1000 °C; 〉15 h). Turbid domains rich in large inclusions change to yellow-brown after heating under oxidizing conditions, while transparent domains remain pale blue or colourless. Optical absorption spectra display sharp absorption lines attributed to U4+, and slightly elevated absorption towards shorter wavelengths. The ~1007 cm−1 ν3(SiO4) Raman band is broadened due to lattice distortion by non-stoichiometric elements in high-Th/-U zircon, whereas narrow bands in inclusion-rich domains indicate a decrease in lattice strain due to inclusion precipitation. Blue colouration in Vesuvius zircon is explained by the effect of light scattering (Rayleigh and/or Mie scattering) on highly refractive actinide-rich inclusions ranging in size from 〈1/10 to few multiples of the wavelengths of visible light. Inclusions likely formed during fluid-mediated coupled dissolution-reprecipitation that locally transformed lattice-strained actinide-rich zircon within several hundreds of years prior to eruption.
    Description: Published
    Description: 21–36
    Description: 1V. Storia eruttiva
    Description: 2V. Struttura e sistema di alimentazione dei vulcani
    Description: 3V. Proprietà chimico-fisiche dei magmi e dei prodotti vulcanici
    Description: 4V. Processi pre-eruttivi
    Description: 5V. Processi eruttivi e post-eruttivi
    Description: 6V. Pericolosità vulcanica e contributi alla stima del rischio
    Description: JCR Journal
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  • 16
    Publication Date: 2021-04-20
    Description: The complexity of coseismic slip distributions influences the tsunami hazard posed by local and, to a certain extent, distant tsunami sources. Large slip concentrated in shallow patches was observed in recent tsunamigenic earthquakes, possibly due to dynamic amplification near the free surface, variable frictional conditions or other factors. We propose a method for incorporating enhanced shallow slip for subduction earthquakes while preventing systematic slip excess at shallow depths over one or more seismic cycles. The method uses the classic k−2 stochastic slip distributions, augmented by shallow slip amplification. It is necessary for deep events with lower slip to occur more often than shallow ones with amplified slip to balance the long-term cumulative slip. We evaluate the impact of this approach on tsunami hazard in the central and eastern Mediterranean Sea adopting a realistic 3D geometry for three subduction zones, by using it to model ~ 150,000 earthquakes with 𝑀𝑤 from 6.0 to 9.0. We combine earthquake rates, depth-dependent slip distributions, tsunami modeling, and epistemic uncertainty through an ensemble modeling technique. We found that the mean hazard curves obtained with our method show enhanced probabilities for larger inundation heights as compared to the curves derived from depth-independent slip distributions. Our approach is completely general and can be applied to any subduction zone in the world.
    Description: Published
    Description: 1497–1520
    Description: 3T. Sorgente sismica
    Description: 6T. Studi di pericolosità sismica e da maremoto
    Description: JCR Journal
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  • 17
    Publication Date: 2020-09-01
    Description: This paper is a final review of the Simplified Ionospheric Regional Model (SIRM) devel- oped as a prototype in the early 1990s and improved in the following years. By means of an algorithm based on the Fourier synthesis, the SIRM model in its prototype version pro- vides predicted monthly median values of the main ionospheric characteristics such as: the ordinary wave critical frequencies (foE, foF1, and foF2) of the E, F1, and F2 ionospheric layers; the lowest virtual height (h’F) of the ordinary trace of the F region; the obliquity factor for a distance of 3000 km (M(3000)F2). Instead, the improved version focuses only on foF2 and M(3000)F2. The SIRM model has been largely employed in the framework of different international research projects as the climatological reference to output foF2 and M(3000)F2 monthly median predictions, but in its SIRMUP version is used also as a nowcasting model and as an intermediate step of complex procedures for a near real- time three-dimensional representation of the ionospheric electron density. In this regard, some results provided by both SIRM and SIRMUP for telecommunication applications are shown. Moreover, the mathematical treatment concerning both the phase correction of the Fourier synthesis and the fundamental steps carried out to define the SIRM algorithm in its final version, never published so far, will be described in detail in dedicated Appendices. Finally, for the first time the SIRM code is now downloadable for the benefit of users.
    Description: Published
    Description: 1143-1178
    Description: 2A. Fisica dell'alta atmosfera
    Description: JCR Journal
    Keywords: SIRM ; SIRMUP ; foF2 ; M(3000)F2 ; Regional modelling ; 01.02. Ionosphere
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 18
    Publication Date: 2020-10-21
    Description: Complex systems (e.g., volcanoes, debris flows, climate) commonly have many models advocated by different modelers and incorporating different modeling assumptions. Limited and sparse data on the modeled phenomena does not permit a clean discrimination among models for fitness of purpose, and, heuristic choices are usually made, especially for critical predictions of behavior that has not been experienced. We advocate here for characterizing models and the modeling assumptions they represent using a statistical approach over the full range of applicability of the models. Such a characterization may then be used to decide the appropriateness of a model for use, and, perhaps as needed weighted compositions of models for better predictive power. We use the example of dense granular representations of natural mass flows in volcanic debris avalanches, to illustrate our approach.
    Description: Published
    Description: 724-736
    Description: 5V. Processi eruttivi e post-eruttivi
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 19
    Publication Date: 2020-11-12
    Description: Slope dynamics in volcanic environments comprise a wide spectrum of phenomena, from large lateral collapse to shallow debris remobilization, which may represent a major threat for human communities and infrastructures. Many volcanos built up from the ocean floor and large portions of the volcano edifice are submerged. In these settings, only the edifice’s summit can be investigated by terrestrial remote sensing and in-situ approaches. Growth and destruction, including tectonics and gravitational phenomena, affect entire volcano flanks and are not limited to the physical boundary of the sea level but could comprise their subaqueous parts.
    Description: Published
    Description: 2615–2618
    Description: 6V. Pericolosità vulcanica e contributi alla stima del rischio
    Description: JCR Journal
    Keywords: volcanoes ; flanks ; volcano-tectonics ; structure ; collapse ; stability ; 04.08. Volcanology ; 05.08. Risk
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 20
    Publication Date: 2020-11-16
    Description: The prehistoric (〈7 ka) Zaro eruption at Ischia island (Southern Italy) produced a lava complex overlaying a pyroclastic deposit. Although being of low energy, the Zaro eruption might have caused casualties among the neolithic population that inhabited that area of Ischia, and damages to their settlements. A similar eruption at Ischia with its present-day population would turn into a disaster. Therefore, understanding the magmatic processes that triggered the Zaro eruption would be important for volcanic hazard assessment and risk mitigation, so as to improve a knowledge that can be applied to other active volcanic areas worldwide. The main Zaro lava body is trachyte and hosts abundant mafc and felsic enclaves. Here all juvenile facies have been fully characterized from petrographic, geochemical and isotopic viewpoints. The whole dataset (major and trace element contents; Sr–Nd isotopic composition) leads to rule out a genetic link by fractional crystallization among the variable facies. Thus, we suggest that the Zaro mafc enclaves could represent a deep-origin mafc magma that mingled/mixed with the main trachytic one residing in the Ischia shallow magmatic system. The intrusion of such a mafc magma into a shallow reservoir flled by partly crystallized, evolved magma could have destabilized the magmatic system presumably acting as a rapid eruption trigger. The resulting processes of convection, mixing and rejuvenation have possibly played an important role in pre- and syn-eruptive phases also in several eruptions of diferent sizes in the Neapolitan area and elsewhere in the world.
    Description: Published
    Description: 2829–2849
    Description: 2V. Struttura e sistema di alimentazione dei vulcani
    Description: 3V. Proprietà chimico-fisiche dei magmi e dei prodotti vulcanici
    Description: 4V. Processi pre-eruttivi
    Description: JCR Journal
    Keywords: Ischia island ; Zaro volcanic complex ; Mineral chemistry ; Isotope geochemistry ; Mafic enclaves
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 21
    Publication Date: 2020-12-21
    Description: In this work, we propose a statistical approach to evaluate the coverage of a network based on the spatial distribution of its nodes and the target information, including all those data related to the final objectives of the network itself. This statistical approach encompasses descriptive spatial statistics in combination with point pattern techniques. As case studies, we evaluate the spatial arrangements of the stations within the Italian National Seismic Network and the Italian Strong Motion Network. Seismic networks are essential tools for observing earthquakes and assessing seismic hazards, while strong motion (accelerometric) networks allow us to describe seismic shaking and to measure the expected effects on buildings and infrastructures. The capability of both networks is a function of an adequate number of optimally distributed stations. We compare the seismic network with the spatial distributions of historical and instrument seismicity and with the distribution of well-known seismogenic sources, and we compare the strong motion station distribution with seismic hazard maps and the population distribution. This simple and reliable methodological approach is able to provide quantitative information on the coverage of any type of network and is able to identify critical areas that require optimization and therefore address areas of future development.
    Description: Published
    Description: 1045–1061
    Description: 1IT. Reti di monitoraggio e sorveglianza
    Description: JCR Journal
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 22
    Publication Date: 2021-06-22
    Description: The densely populated Po Plain, a very deep sedi- mentary basin in northern Italy, is prone to heavy shaking during earthquakes. Seismic hazard assessment must account for local variation in wave amplification. Standard ground motion prediction equations may fail to picture the complexity of strong lateral gradients in seismic response, due to sharp structural heterogeneity. For this reason, there is an increasing demand for full waveform predictions for engineering applications. Here, we present an implementation of a hybrid broadband simulation based on the method of Mai et al. (Bull Seismol Soc Am 100(6):3338–3339, 2010), to obtain complete broadband seismograms of 0.1–10 Hz. With this method, low frequency (〈1 Hz) and high frequency (1–10 Hz) seismograms are simulated separately using a deter- ministic and a stochastic method, respectively. We apply the method to four events recorded within the Po basin, with magnitude ranging from Mw = 4.4 to Mw = 5.6. The low frequency (LF) simulation is performed using SPECFEM3D on a few test sub- surface velocity models. The three-dimensional velocity model MAMBo (Molinari et al. in Bull Seismol Soc Am 105(2A):753–764, 2015)—consisting of a detailed structural description of the basin, based on extensive active-source data, embedded within a regional 3D crustal model—provided the best results for broadband simulations that most closely corresponded with the observations. It performed better than an ambient noise tomography model with more accurate S-wave velocities but less well defined layer topographies, emphasizing the importance of first order velocity discontinuities. The high frequency (HF) seis- mograms are simulated using the multiple scattering approach of Zeng et al. (J Geophys Res Solid Earth 96(B1):607–619, 1991). The scattering coefficients are obtained by performing a non linear inversion for each station to find best fitting synthetic envelopes. HF energy is then combined at 1 Hz to match the amplitude and phase spectra of the LF signal. We are able to simulate full waveforms throughout the Po Plain, of which shaking duration matches observed data for stations located in the basin. Shaking amplitudes are generally overestimated in the low frequency simulation by the MAMBo velocity model. Updating the MAMBo velocity model with more accurate S-wave velocity information of the ambient noise tomography model should improve the fit in future simulations.
    Description: Published
    Description: 2181–2198
    Description: 1T. Struttura della Terra
    Description: JCR Journal
    Keywords: Ground motion ; hybrid method ; sedimentary basin ; Seismic shaking scenario ; 04. Solid Earth
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 23
    Publication Date: 2020-08-06
    Description: With globally growing aquaculture activities, the co-introduction of parasites alongside large-scale movements of commercial species poses an increasing risk for marine ecosystems. Here, we present the first record of the shell-boring polychaete Polydora websteri Hartman in Loosanoff and Engle, 1943 in invasive Pacific oysters Crassostrea (Magallana) gigas (Thunberg, 1793) in the European Atlantic Ocean. In October 2014, mud blisters in the shells of wild Pacific oysters and specimens of a spionid polychaete were observed in close proximity to a commercial oyster farm at the island of Sylt (Germany) in the European Wadden Sea. Subsequent investigations indicated that these blisters only occurred near the farm and that no other mollusc species were affected. Morphological and molecular analysis identified the polychaete as Polydora websteri, a species that nowadays widely occurs around the globe, but likely is native to the Asian Pacific. Later sampling activities detected P. websteri also at other locations around Sylt as well as in the Dutch part of the Wadden Sea at the island of Texel. The number of polychaetes in the oysters was, however, relatively low and mostly below 10 individuals per oyster. Together, this evidence suggests that P. websteri is currently extending its range. As the introduction of P. websteri may have severe ecological and economic implications, this study aims to alert others to look for P. websteri at Western European coasts within farmed or wild Pacific oysters to further document its spread.
    Repository Name: EPIC Alfred Wegener Institut
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  • 24
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    In:  EPIC3Advances in Atmospheric Sciences, Springer, 37(5), pp. 455-476, ISSN: 0256-1530
    Publication Date: 2020-07-13
    Description: Atmospheric rivers (ARs) are an important component of the hydrological cycle linking moisture sources in lowerlatitudes to the Antarctic surface mass balance. We investigate AR signatures in the atmospheric vertical profiles at theDronning Maud Land coast, East Antarctica, using regular and extra radiosonde measurements conducted during the Yearof Polar Prediction Special Observing Period November 2018 to February 2019. Prominent AR events affecting thelocations of Neumayer and Syowa cause a strong increase in specific humidity extending through the mid-troposphere anda strong low-level jet (LLJ). At Neumayer, the peak in the moisture inversion (up to 4 g kg−1) is observed between 800 and900 hPa, while the LLJ (up to 32 m s−1) is concentrated below 900 hPa. At Syowa the increase in humidity is lesspronounced and peaks near the surface, while there is a substantial increase in wind speed (up to 40 m s−1) between 825 and925 hPa. Moisture transport (MT) within the vertical profile during the ARs attains a maximum of 100 g kg−1 m s−1 at bothlocations, and is captured by both ERA-Interim and ERA5 reanalysis data at Neumayer, but is strongly underestimated atSyowa. Composites of the enhanced MT events during 2009−19 show that these events represent an extreme state of thelower-tropospheric profile compared to its median values with respect to temperature, humidity, wind speed and,consequently, MT. High temporal- and vertical-resolution radiosonde observations are important for understanding thecontribution of these rare events to the total MT towards Antarctica and improving their representation in models.
    Repository Name: EPIC Alfred Wegener Institut
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  • 25
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    In:  EPIC3Cham, Springer, 378 p., ISBN: 978-3-030-20389-4
    Publication Date: 2020-06-12
    Description: This open access book summarizes peer-reviewed articles and the abstracts of oral and poster presentations given during the YOUMARES 9 conference which took place in Oldenburg, Germany, in September 2018. The aims of this book are to summarize state-of-the-art knowledge in marine sciences and to inspire scientists of all career stages in the development of further research. These conferences are organized by and for young marine researchers. Qualified early-career researchers, who moderated topical sessions during the conference, contributed literature reviews on specific topics within their research field.
    Repository Name: EPIC Alfred Wegener Institut
    Type: Book , peerRev
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  • 26
    Publication Date: 2020-10-15
    Description: Surface water characteristics of the Beaufort Sea have global climate implications during the last deglaciation and the Holocene, as (1) sea ice is a critical component of the climate system and (2) Laurentide Ice Sheet meltwater discharges via the Mackenzie River to the Arctic Ocean and further, to its outflow near the deep-water source area of the Atlantic Meridional Overturning Circulation. Here we present high-resolution biomarker records from the southern Beaufort Sea. Multi-proxy biomarker reconstruction suggests that the southern Beaufort Sea was nearly ice-free during the deglacial to Holocene transition, and a seasonal sea-ice cover developed during the mid-late Holocene. Superimposed on the long-term change, two events of high sediment flux were documented at ca. 13 and 11 kyr BP, respectively. The first event can be attributed to the Younger Dryas flood and the second event is likely related to a second flood and/or coastal erosion.
    Repository Name: EPIC Alfred Wegener Institut
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  • 27
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    In:  EPIC3Physics and Chemistry of the Arctic Atmosphere, Physics and Chemistry of the Arctic Atmosphere, Springer, pp. 1-51, ISBN: 978-3-030-33566-3
    Publication Date: 2020-02-05
    Description: This book presents current knowledge on chemistry and physics of Arctic atmosphere. Special attention is given to studies of the Arctic haze phenomenon, Arctic tropospheric clouds, Arctic fog, polar stratospheric and mesospheric clouds, atmospheric dynamics, thermodynamics and radiative transfer as related to the polar environment. The atmosphere-cryosphere feedbacks and atmospheric remote sensing techniques are presented in detail. The problems of climate change in the Arctic are also addressed.
    Repository Name: EPIC Alfred Wegener Institut
    Type: Inbook , peerRev
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  • 28
    Publication Date: 2020-05-11
    Description: Satellite altimetry has been widely used to determine surface elevation changes in polar ice sheets. The original height measurements are irregularly distributed in space and time. Gridded surface elevation changes are commonly derived by repeat altimetry analysis (RAA) and subsequent spatial interpolation of height change estimates. This article assesses how methodological choices related to those two steps affect the accuracy of surface elevation changes, and how well this accuracy is represented by formal uncertainties. In a simulation environment resembling CryoSat-2 measurements acquired over a region in northeast Greenland between December 2010 and January 2014, different local topography modeling approaches and different cell sizes for RAA, and four interpolation approaches are tested. Among the simulated cases, the choice of either favorable or unfavorable RAA affects the accuracy of results by about a factor of 6, and the different accuracy levels are propagated into the results of interpolation. For RAA, correcting local topography by an external digital elevation model (DEM) is best, if a very precise DEM is available, which is not always the case. Yet the best DEM-independent local topography correction (nine-parameter model within a 3,000 m diameter cell) is comparable to the use of a perfect DEM, which exactly represents the ice sheet topography, on the same cell size. Interpolation by heterogeneous measurement-error-filtered kriging is significantly more accurate (on the order of 50% error reduction) than interpolation methods, which do not account for heterogeneous errors.
    Repository Name: EPIC Alfred Wegener Institut
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  • 29
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    In:  EPIC3Antarctic Seaweeds Diversity, Adaptation and Ecosystem Services, Antarctic Seaweeds, Cham, Switzerland, Springer, 397 p., pp. 241-264, ISBN: 978-3-030-39447-9
    Publication Date: 2020-06-10
    Repository Name: EPIC Alfred Wegener Institut
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  • 30
    Publication Date: 2021-05-21
    Description: The Beenchime-Salaatinsky Crater (BSC) is located west of the Olenyok River in Northern Yakutia, ~ 260 km south-west of Tiksi and the Lena Delta. The age and origin (volcanic versus meteoritic) of this crater is poorly understood. The key scientific interest in re-visiting the BSC is the reappraisal of the Quaternary sedimentation dynamics for a better understanding of the sediment history and thickness in the basin. This aides for an assessment, if the site is prospective for a deeper drilling of a Quaternary (or Cenozoic) sediment archive. Soil pits and auger cores from slopes and lowland terrain in the basin were sampled and studied to infer sediment ages and transport dynamics. This also included a thermokarst lake placed in the centre of the basin. Studied properties include grain-size distribution, organic carbon and nitrogen contents (TOC and TN), heavy mineral compositions, δ13C of organic carbon, 14C ages from sediment, δ18O and δD from ground ice and waters, and lake bathymetry from GPR profiling, in addition. We conclude that the crater floor in the BSC is underlain by fluvial/alluvial sediments from the MIS 3 period. Thermokarst lake formation took place during the Holocene Thermal Maximum between 7600 and 6100 cal yr BP. The lake has been shrinking hereafter. Fluvial/alluvial sedimentation along the drainage pattern was active again between 5700 to 1500 cal yr BP, and it was flanked by the accumulation of peaty and organic-rich sediments and the formation of ice-wedge polygons.
    Repository Name: EPIC Alfred Wegener Institut
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  • 31
    Publication Date: 2020-02-11
    Description: Prediction patterns are generated using different data sets from a database for landslides hazard in northern Italy. A direct supporting pattern of the distribution of 28 complex landslides was previously used to obtain their spatial relationships with five categorical indirect supporting patterns representing the spatial context of the landslides: geology, land use, and permeability in addition to internal relief and slope, the latter two categorized into five classes. The five indirect supporting patterns were selected to minimize the effects of conditional dependence on prediction patterns by a Weight-of-Evidence model. The same set of patterns is reanalysed applying the Empirical Likelihood Ratio model using also uncategorized continuous supporting patterns: aspect, curvature, and digital elevation, in addition to internal relief and slope. The resulting prediction patterns are compared in terms of prediction rates and target-uncertainty patterns.
    Description: Published
    Description: 291-294
    Description: 2TR. Ricostruzione e modellazione della struttura crostale
    Description: N/A or not JCR
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 32
    Publication Date: 2020-02-20
    Description: Tsunamis are low-frequency high-consequences major natural threats, rare events devastating vast coastal regions near and far from their generation areas. They may be caused by coseismic seafloor motions, subaerial and submarine mass movements, volcanic activities (like explosions, pyroclastic flows and caldera collapses), meteorological phenomena and meteorite ocean impacts. The probability of tsunami occurrence and/or impact on a given coast may be treated formally by combining calculations based on empirical observations and on models; this probability can be updated in light of new/independent information. This is the general concept of the Bayesian method applied to tsunami probabilistic hazard analysis, which also provides a direct quantification of forecast uncertainties. This entry presents a critical overview of Bayesian procedures with a primary focus on their appropriate and relevant applicability to tsunami hazard analyses.
    Description: Published
    Description: 6T. Studi di pericolosità sismica e da maremoto
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 33
    Publication Date: 2020-06-10
    Description: Use of faults in seismic hazard models allows us to capture the recurrence of large-magnitude events and therefore improve the reliability of probabilistic seismic hazard assessment (PSHA). In the past decades, fault segmentation provided an important framework for quantifying fault-based PSHA. Recent complex coseismic ruptures (e.g., 2010 Mw 7.1 Canterbury, 2012 Mw 8.6 Sumatra, 2016 Mw 7.8 Kaikōura, 2016 Mw 6.5 central Italy) have shown the need to consider different possible combinations of rupture scenarios in PSHA. Here we present two new methodologies that model rates of ruptures along complex fault systems, one based on a floating rupture approach (FRESH) and another one based on assumed rupture scenarios (SUNFISH). They represent alternatives to a recently proposed approach (SHERIFS), and further step to overcome the segmented and un-segmented approaches commonly used in PSHA in Europe. Differences among SHERIFS, SUNFiSH and FRESH are related to the way slip rate, rupture geometries and magnitude–frequency distributions are modelled. To quantify the differences between these three methodologies, we compared PSHA results based on geometries and slip rates of a fault system located in northeastern Italy, assuming a given maximum magnitude and the same seismic moment rate target. Differences up to 20–30% in the peak ground acceleration at 2% and 10% in 50 years are observed. Finally, we show that the three methodologies are able to solve for the long-term rate of ruptures with resulting PSHA that reflect the fault system geometry and slip rates, without any assumption on segment boundaries. Using fault-based approaches in PSHA requires collecting as much local geological information as possible. Now that multi-fault rupture approaches are available, simplifying assumptions often made to model complex fault systems (uniform slip rate, segmentation hypothesis) are no longer necessary. On the other hand, local data collection should be strongly encouraged to better characterize the actual fault slip rate variability and the complex 3D geometrie
    Description: Published
    Description: 1855–1877
    Description: 6T. Studi di pericolosità sismica e da maremoto
    Description: JCR Journal
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  • 34
    Publication Date: 2020-03-03
    Description: A critical point in the analysis of ground dis- placement time series, as those recorded by space geodetic techniques, is the development of data-driven methods that allow the different sources of deformation to be discerned and characterized in the space and time domains. Multivariate statistic includes several approaches that can be considered as a part of data-driven methods. A widely used technique is the principal component analysis (PCA), which allows us to reduce the dimensionality of the data space while maintain- ing most of the variance of the dataset explained. However, PCA does not perform well in finding the solution to the so-called blind source separation (BSS) problem, i.e., in recovering and separating the original sources that gener- ate the observed data. This is mainly due to the fact that PCA minimizes the misfit calculated using an L 2 norm (χ 2 ), look- ing for a new Euclidean space where the projected data are uncorrelated. The independent component analysis (ICA) is a popular technique adopted to approach the BSS problem. However, the independence condition is not easy to impose, and it is often necessary to introduce some approximations. To work around this problem, we test the use of a modi- fied variational Bayesian ICA (vbICA) method to recover the multiple sources of ground deformation even in the presence of missing data. The vbICA method models the probability density function (pdf) of each source signal using a mix of Gaussian distributions, allowing for more flexibility in the description of the pdf of the sources with respect to standard ICA, and giving a more reliable estimate of them. Here we present its application to synthetic global positioning system (GPS) position time series, generated by simulating deforma- tion near an active fault, including inter-seismic, co-seismic, and post-seismic signals, plus seasonal signals and noise, and an additional time-dependent volcanic source. We evaluate the ability of the PCA and ICA decomposition techniques in explaining the data and in recovering the original (known) sources. Using the same number of components, we find that the vbICA method fits the data almost as well as a PCA method, since the χ 2 increase is less than 10 % the value cal- culated using a PCA decomposition. Unlike PCA, the vbICA algorithm is found to correctly separate the sources if the correlation of the dataset is low (〈0.67) and the geodetic network is sufficiently dense (ten continuous GPS stations within a box of side equal to two times the locking depth of a fault where an earthquake of Mw 〉 6 occurred). We also provide a cookbook for the use of the vbICA algorithm in analyses of position time series for tectonic and non-tectonic applications.
    Description: Published
    Description: 323–341
    Description: 1T. Struttura della Terra
    Description: 2T. Deformazione crostale attiva
    Description: JCR Journal
    Keywords: 04. Solid Earth ; 04.03. Geodesy
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  • 35
    Publication Date: 2020-03-04
    Description: The SabatiniVolcanicDistrict (SVD), active between 0.8 and 0.07 Ma, is a volcanic field in the Roman province (Central Italy) located along the Tyrrhenian margin of the Italian peninsula. In this volcanic region, high-K magmas originated from a metasomatised phlogopite-bearing peridotite mantle recording subduction-related fluids and/or melting processes. Here, we investigate magma evolution during the six main eruptive phases of the SVD by means of chemical and isotopic (Sr and Nd) analyses. Specifically, we analyzed clinopyroxene crystals from juvenile pumice and scoria clasts and lavas, from 40 major SVD eruptive units chronologically well constrained by 40Ar/39Ar dating. 87Sr/86Sr and 144Nd/143Nd ratios in SVDclinopyroxene range 0.7095–0.7115 and 0.51210- 0.51214, respectively. The mean Sr and Nd isotope compositions of each eruptive phases show a gradual, long-term decrease over the entire SVD eruptive history. However, when considering the distinct temporal windows of the individual eruptive phases, a significant variability of the Sr-Nd isotope ratios emerges, thus highlighting a more complex, time-dependent geochemical trend for the erupted magmas,with respect to a previously described trend at the nearby Colli AlbaniVolcanic District (0.6–0.04 Ma). Geochemical features of clinopyroxene in lavas and juvenile pyroclasts suggest that magma differentiation occurred in an open system due to assimilation of siliciclastic sedimentary rocks. Moreover, a critical review of the available geochemical data, in light of 40Ar/39Ar ages, allows the recognition of the SVD as the source of widespread tephra markers recorded in the central Mediterranean area by previous works.
    Description: Published
    Description: id 67
    Description: 1V. Storia eruttiva
    Description: JCR Journal
    Keywords: Sabatini Volcanic District ; Roman province ; Sr and Nd isotopes
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  • 36
    Publication Date: 2020-07-02
    Description: We contribute to the debate on the identification of phase scintillation induced by the ionosphere on the Global Navigation Satellite System (GNSS) by introducing a phase detrending method able to provide realistic values of the phase scintillation index at high latitude. It is based on the Fast Iterative Filtering (FIF) signal decomposition technique, which is a recently developed fast implementation of the well-established Adaptive Local Iterative Filtering (ALIF) algorithm. FIF has been conceived to decompose nonstationary signals efficiently and providing a discrete set of oscillating functions, each of them having its frequency. It overcomes most of the problems that arise when using traditional time-frequency analysis techniques and relies on a consolidated mathematical basis since its a priori convergence and stability have been proved. By relying on the capability of FIF to efficiently identify the frequencies embedded in the GNSS raw phase, we define a method based on the FIF-derived spectral features to identify the proper cutoff frequency for phase detrending. To test such a method, we analyze the data acquired from GPS and Galileo signals over Antarctica during the September 2017 storm by the Ionospheric Scintillation Monitor Receiver (ISMR) located in Concordia Station (75.10°S, 123.33°E). Different cases of diffraction and refraction effects are provided, showing the capability of the method in deriving a more accurate determination of the SigmaPhi index. We found values of cutoff frequency in the range of 0.73 to 0.83 Hz, providing further evidence of the inadequacy of the choice of 0.1 Hz, which is often used when dealing with ionospheric scintillation monitoring at high latitudes.
    Description: This research is supported by TREASURE, a project funded by the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Actions grant agreement n.722023 (http://ww.treasure-gnss.eu).
    Description: Published
    Description: id 85
    Description: 2TM. Divulgazione Scientifica
    Description: JCR Journal
    Keywords: ionospheric scintillation · plasma drift velocity · scintillation indices · refractive and diffractive effects · Galileo and GPS signals · data detrending ; Disentangling ionospheric refraction and diffraction effects in GNSS raw phase through fast iterative filtering technique
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 37
    Publication Date: 2020-07-13
    Description: A possible driver of precipitation of magnetospheric energetic electrons in the high-latitude atmosphere is represented by electromagnetic ion-cyclotron (EMIC) magnetospheric waves. The precipitating particles produce variations, by collision, in the ionized component of the atmosphere, altering its chemistry and electrical conductivity, with a significant impact on the atmospheric processes. In this framework, it would be significant to find experimental evidence of a correspondence between ionospheric electron density irregularities and the occurrence of Ultra-Low-Frequency (ULF) Pc1 geomagnetic pulsations, i.e., the ground signatures of EMIC waves, at high latitudes. In this work, we face this subject by considering a specific case study occurred on 22 February 2007 during quiet magnetospheric conditions. The study is based on the analysis of simultaneous ULF geomagnetic field and Total Electron Content (TEC) measurements recorded at Mario Zucchelli Station in Antarctica. We show that Pc1 pulsations occur in correspondence to solar wind pressure increases and that, at the same time, the ionosphere is characterized by the presence of ionospheric irregularities. We suggest that a possible link between the Pc1 activity and the ionospheric irregularities may be energetic electron precipitations, driven by EMIC waves generated in the compressed magnetosphere, which produce density variations in the ionized component of the atmosphere.
    Description: Published
    Description: id 59
    Description: 1A. Geomagnetismo e Paleomagnetismo
    Description: 2A. Fisica dell'alta atmosfera
    Description: JCR Journal
    Repository Name: Istituto Nazionale di Geofisica e Vulcanologia (INGV)
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  • 38
    Publication Date: 2020-02-10
    Description: RAD7 and BigBottle system has been developed, using large glass bottles, but these are fragile and awkward to carry around. In searching for a better solution, we tested polyethylene terephthalate (PET) bottles for water samples storage to estimate radon loss over time. Two sets of experiments with 0.355 and 1.75 L bottles demonstrated that PET is a suitable material for storage. If correction for 226Ra content in water is applied, we can also calculate the rate of radon loss (0.03 ± 0.08 % day-1).
    Description: Published
    Description: 2277-2280
    Description: 2IT. Laboratori analitici e sperimentali
    Description: JCR Journal
    Keywords: Polyethylene terephthalate ; Radon loss from water during storage ; RAD7 ; BigBottle RADH2O ; 05.04. Instrumentation and techniques of general interest
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  • 39
    Publication Date: 2020-03-09
    Description: Plastic has become indispensable for human life. When plastic debris is discarded into waterways, these items can interact with organisms. Of particular concern are microscopic plastic particles (microplastics) which are subject to ingestion by several taxa. This review summarizes the results of cutting-edge research about the interactions between a range of aquatic species and microplastics, including effects on biota physiology and secondary ingestion. Uptake pathways via digestive or ventilatory systems are discussed, including (1) the physical penetration of microplastic particles into cellular structures, (2) leaching of chemical additives or adsorbed persistent organic pollutants (POPs), and (3) consequences of bacterial or viral microbiota contamination associated with microplastic ingestion. Following uptake, a number of individual-level effects have been observed, including reduction of feeding activities, reduced growth and reproduction through cellular modifications, and oxidative stress. Microplastic-associated effects on marine biota have become increasingly investigated with growing concerns regarding human health through trophic transfer. We argue that research on the cellular interactions with microplastics provide an understanding of their impact to the organisms’ fitness and, therefore, its ability to sustain their functional role in the ecosystem. The review summarizes information from 236 scientific publications. Of those, only 4.6% extrapolate their research of microplastic intake on individual species to the impact on ecosystem functioning. We emphasize the need for risk evaluation from organismal effects to an ecosystem level to effectively evaluate the effect of microplastic pollution on marine environments. Further studies are encouraged to investigate sublethal effects in the context of environmentally relevant microplastic pollution conditions.
    Repository Name: EPIC Alfred Wegener Institut
    Type: Book , peerRev
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  • 40
    Publication Date: 2020-03-13
    Description: Arctic sea ice is a critical component of the climate system, known to in uence ocean circulation, earth’s albedo, and ocean–atmosphere heat and gas exchange. Current developments in the use of IP25 (a sea ice proxy with 25 carbon atoms only synthesized by Arctic sea ice diatoms) have proven it to be a suitable proxy for paleo-sea ice reconstructions over hundreds of thousands to even millions of years. In the NE Baffin Bay, off NW Greenland, Melville Bugt is a climate-sensitive region characterized by strong seasonal sea ice variability and strong melt-water discharge from the Greenland Ice Sheet (GIS). Here, we present a centennial-scale resolution Holocene sea ice record, based on IP25 and open-water phytoplankton biomarkers (brassicasterol, dinosterol and HBI III) using core GeoB19927-3 (73° 35.26′ N, 58° 05.66′ W). Seasonal to ice-edge conditions near the core site are documented for most of the Holocene period with some significant variability. In the lower-most part, a cold interval characterized by extensive sea ice cover and very low local productivity is succeeded by an interval (~ 9.4–8.5 ka BP) with reduced sea ice cover, enhanced GIS spring melting, and strong in uence of the West Greenland Current (WGC). From ~ 8.5 until ~ 7.8 ka BP, a cooling event is recorded by ice algae and phytoplankton biomarkers. They indicate an extended sea ice cover, possibly related to the opening of Nares Strait, which may have led to an increased influx of Polar Water into NE-Baffin Bay. The interval between ~ 7.8 and ~ 3.0 ka BP is characterized by generally reduced sea ice cover with millennial-scale variability of the (late winter/early spring) ice-edge limit, increased open-water conditions (polynya type), and a dominant WGC carrying warm waters at least as far as the Melville Bugt area. During the last ~ 3.0 ka BP, our biomarker records do not reflect the late Holocene ‘Neoglacial cooling’ observed elsewhere in the Northern Hemisphere, possibly due to the persistent influence of the WGC and interactions with the adjacent fjords. Peaks in HBI III at about ~ 2.1 and ~ 1.3 ka BP, interpreted as persistent ice-edge situations, might correlate with the Roman Warm Period (RWP) and Medieval Climate Anomaly (MCA), respectively, in-phase with the North Atlantic Oscillation (NAO) mode. When integrated with marine and terrestrial records from other circum-Baffin Bay areas (Disko Bay, the Canadian Arctic, the Labrador Sea), the Melville Bugt biomarker records point to close ties with high Arctic and Northern Hemispheric climate conditions, driven by solar and oceanic circulation forcings.
    Repository Name: EPIC Alfred Wegener Institut
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  • 41
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    Springer
    In:  EPIC3Bulletin of Atmospheric Science and Technology, Springer, ISSN: 2662-1495
    Publication Date: 2020-05-27
    Description: In situ profiles and fixed-altitude time series of all four components of net radiation were obtained at Ny-Ålesund, Svalbard (78.9° N, 11.9° E), in the period May 04–21, 2015. Measurements were performed using adapted high-quality instrumentation classified as “secondary standard” carried by a tethered balloon system. Balloon-lifted measurements of albedo under clear-sky conditions demonstrate the local dependence on altitude and on the surface inhomogeneity of this parameter over coastal terrain of Ny-Ålesund. Depending on the surface composition within the sensor’s footprint near the coastline, the albedo over predominantly snow-covered surfaces was found to decrease to 0.548 and 0.452 at 494 m and 881 m altitude compared with 0.731 and 0.788 measured with near-surface references, respectively. Albedo profiles show an all-sky maximum at 150 m above surface level due to local surface inhomogeneity, and an averaged vertical change rate of − 0.040/100 up to 750 m aboveground level (clear sky) and − 0.034/100 m (overcast). Profiling of arctic low-level clouds reveals distinct vertical gradients in all radiative fluxes but longwave upward at the cloud top. Observed radiative cooling at the top of a partly dissolving stratus cloud with heating rates of − 40.4 to − 62.1 Kd−1 in subsequent observations is exemplified.
    Repository Name: EPIC Alfred Wegener Institut
    Type: Article , isiRev
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  • 42
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    Springer
    In:  ISSI Scientific Report Series
    Publication Date: 2020-05-09
    Description: This open access book provides a comprehensive toolbox of analysis techniques for ionospheric multi-satellite missions. The immediate need for this volume was motivated by the ongoing ESA Swarm satellite mission, but the tools that are described are general and can be used for any future ionospheric multi-satellite mission with comparable instrumentation. In addition to researching the immediate plasma environment and its coupling to other regions, such a mission aims to study the Earth’s main magnetic field and its anomalies caused by core, mantle, or crustal sources. The parameters for carrying out this kind of work are examined in these chapters. Besides currents, electric fields, and plasma convection, these parameters include ionospheric conductance, Joule heating, neutral gas densities, and neutral winds.
    Type: info:eu-repo/semantics/book
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  • 43
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    Springer
    In:  Earth & Environmental Science
    Publication Date: 2020-05-14
    Description: This book is the second edition of the well-known textbook Modelling Rock Fracturing Processes. The new and extended edition provides the theoretical background of rock fracture mechanics used for modelling of 2-D and 3-D geomechanics problems and processes. Fundamentals of rock fracture mechanics integrated with experimental studies of rock fracturing processes are highlighted. The computer programs FRACOD 2D and 3D are used to analyse fracture initiation and propagation for the three fracture modes: Mode I, II and III. Coupled fracture modelling with other continuous and distinct element codes including FLAC, PFC, RFPA, TOUGH are also described. A series of applications of fracture modelling with importance for modern society is presented and discussed by distinguished rock fracture modelling experts.
    Type: info:eu-repo/semantics/book
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  • 44
    Publication Date: 2020-05-15
    Description: Amyloidoses (misfolded polypeptide accumulation) are among the most debilitating diseases our aging societies face. Amyloidogenesis can be catalyzed by hydrophobic–hydrophilic interfaces (e.g., air–water interface in vitro [AWI]). We recently demonstrated hydrogelation of the amyloidogenic type II diabetes-associated islet amyloid polypeptide (IAPP), a hydrophobic–hydrophilic interface-dependent process with complex kinetics. We demonstrate that human IAPP undergoes AWI-catalyzed liquid–liquid phase separation (LLPS), which initiates hydrogelation and aggregation. Insulin modulates these processes but does not prevent them. Using nonamyloidogenic rat IAPP, we show that, whereas LLPS does not require the amyloidogenic sequence, hydrogelation and aggregation do. Interestingly, both insulin and rat sequence delayed IAPP LLPS, which may reflect physiology. By developing an experimental setup and analysis tools, we show that, within the whole system (beyond the droplet stage), macroscopic interconnected aggregate clusters form, grow, fuse, and evolve via internal rearrangement, leading to overall hydrogelation. As the AWI-adsorbed gelled layer matures, its microviscosity increases. LLPS-driven aggregation may be a common amyloid feature and integral to pathology.
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  • 45
    Publication Date: 2020-06-15
    Description: Human speech production requires the ability to couple motor actions with their auditory consequences. Nonhuman primates might not have speech because they lack this ability. To address this question, we trained macaques to perform an auditory–motor task producing sound sequences via hand presses on a newly designed device (“monkey piano”). Catch trials were interspersed to ascertain the monkeys were listening to the sounds they produced. Functional MRI was then used to map brain activity while the animals listened attentively to the sound sequences they had learned to produce and to two control sequences, which were either completely unfamiliar or familiar through passive exposure only. All sounds activated auditory midbrain and cortex, but listening to the sequences that were learned by self-production additionally activated the putamen and the hand and arm regions of motor cortex. These results indicate that, in principle, monkeys are capable of forming internal models linking sound perception and production in motor regions of the brain, so this ability is not special to speech in humans. However, the coupling of sounds and actions in nonhuman primates (and the availability of an internal model supporting it) seems not to extend to the upper vocal tract, that is, the supralaryngeal articulators, which are key for the production of speech sounds in humans. The origin of speech may have required the evolution of a “command apparatus” similar to the control of the hand, which was crucial for the evolution of tool use.
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  • 46
    Publication Date: 2020-02-28
    Description: Induction of longstanding immunologic tolerance is essential for survival of transplanted organs and tissues. Despite recent advances in immunosuppression protocols, allograft damage inflicted by antibody specific for donor organs continues to represent a major obstacle to graft survival. Here we report that activation of regulatory CD8 T cells (CD8 Treg) that recognize the Qa-1 class Ib major histocompatibility complex (MHC), a mouse homolog of human leukocyte antigen-E (HLA-E), inhibits antibody-mediated immune rejection of heart allografts. We analyzed this response using a mouse model that harbors a point mutation in the class Ib MHC molecule Qa-1, which disrupts Qa-1 binding to the T cell receptor (TCR)–CD8 complex and impairs the CD8 Treg response. Despite administration of cytotoxic T lymphocyte antigen 4 (CTLA-4) immunoglobulin (Ig), Qa-1 mutant mice developed robust donor-specific antibody responses and accelerated heart graft rejection. We show that these allo-antibody responses reflect diminished Qa-1–restricted CD8 Treg-mediated suppression of host follicular helper T cell-dependent antibody production. These findings underscore the critical contribution of this Qa-1/HLA-E-dependent regulatory pathway to maintenance of transplanted organs and suggest therapeutic approaches to ameliorate allograft rejection.
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  • 47
    Publication Date: 2020-06-29
    Description: Under steady-state conditions, the immune system is poised to sense and respond to the microbiota. As such, immunity to the microbiota, including T cell responses, is expected to precede any inflammatory trigger. How this pool of preformed microbiota-specific T cells contributes to tissue pathologies remains unclear. Here, using an experimental model of psoriasis, we show that recall responses to commensal skin fungi can significantly aggravate tissue inflammation. Enhanced pathology caused by fungi preexposure depends on Th17 responses and neutrophil extracellular traps and recapitulates features of the transcriptional landscape of human lesional psoriatic skin. Together, our results propose that recall responses directed to skin fungi can directly promote skin inflammation and that exploration of tissue inflammation should be assessed in the context of recall responses to the microbiota.
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  • 48
  • 49
    Publication Date: 2020-06-25
    Description: Low availability of nitrogen (N) is often a major limiting factor to crop yield in most nutrient-poor soils. Arbuscular mycorrhizal (AM) fungi are beneficial symbionts of most land plants that enhance plant nutrient uptake, particularly of phosphate. A growing number of reports point to the substantially increased N accumulation in many mycorrhizal plants; however, the contribution of AM symbiosis to plant N nutrition and the mechanisms underlying the AM-mediated N acquisition are still in the early stages of being understood. Here, we report that inoculation with AM fungusRhizophagus irregularisremarkably promoted rice (Oryza sativa) growth and N acquisition, and about 42% of the overall N acquired by rice roots could be delivered via the symbiotic route under N-NO3−supply condition. Mycorrhizal colonization strongly induced expression of the putative nitrate transporter geneOsNPF4.5in rice roots, and its orthologsZmNPF4.5inZea maysandSbNPF4.5inSorghum bicolor. OsNPF4.5 is exclusively expressed in the cells containing arbuscules and displayed a low-affinity NO3−transport activity when expressed inXenopus laevisoocytes. Moreover, knockout ofOsNPF4.5resulted in a 45% decrease in symbiotic N uptake and a significant reduction in arbuscule incidence when NO3−was supplied as an N source. Based on our results, we propose that the NPF4.5 plays a key role in mycorrhizal NO3−acquisition, a symbiotic N uptake route that might be highly conserved in gramineous species.
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  • 50
    Publication Date: 2020-06-29
    Description: Folate deprivation drives the instability of a group of rare fragile sites (RFSs) characterized by CGG trinucleotide repeat (TNR) sequences. Pathological expansion of the TNR within theFRAXAlocus perturbs DNA replication and is the major causative factor for fragile X syndrome, a sex-linked disorder associated with cognitive impairment. Although folate-sensitive RFSs share many features with common fragile sites (CFSs; which are found in all individuals), they are induced by different stresses and share no sequence similarity. It is known that a pathway (termed MiDAS) is employed to complete the replication of CFSs in early mitosis. This process requires RAD52 and is implicated in generating translocations and copy number changes at CFSs in cancers. However, it is unclear whether RFSs also utilize MiDAS and to what extent the fragility of CFSs and RFSs arises by shared or distinct mechanisms. Here, we demonstrate that MiDAS does occur atFRAXAfollowing folate deprivation but proceeds via a pathway that shows some mechanistic differences from that at CFSs, being dependent on RAD51, SLX1, and POLD3. A failure to complete MiDAS atFRAXAleads to severe locus instability and missegregation in mitosis. We propose that break-induced DNA replication is required for the replication ofFRAXAunder folate stress and define a cellular function for human SLX1. These findings provide insights into how folate deprivation drives instability in the human genome.
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  • 51
    Publication Date: 2020-01-28
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  • 52
    Publication Date: 2020-03-10
    Description: Necroptosis is a regulated necrotic cell death pathway involved in development and disease. Its signaling cascade results in the formation of disulfide bond-dependent amyloid-like polymers of mixed lineage kinase domain-like protein (MLKL), which mediate proinflammatory cell membrane disruption. We screened compound libraries provided by the National Cancer Institute and identified a small-molecule inhibitor of necroptosis named necroptosis-blocking compound 1 (NBC1). Biotin-labeled NBC1 specifically conjugates to heat shock protein Hsp70. NBC1 and PES-Cl, a known Hsp70 substrate-binding inhibitor, block the formation of MLKL polymers, but not MLKL tetramers in necroptosis-induced cells. In vitro,recombinant Hsp70 interacts with the N-terminal domain (NTD) of MLKL and promotes NTD polymerization, which has been shown to mediate the cell killing activity. Furthermore, the substrate-binding domain (SBD) of Hsp70 is sufficient to promote MLKL polymerization. NBC1 covalently conjugates cysteine 574 and cysteine 603 of the SBD to block its function. In addition, an SBD mutant with both cysteines mutated to serines loses its ability to promote MLKL polymerization. Interestingly, knockdown of Hsp70 in cells leads to MLKL destabilization, suggesting that MLKL might also be a client protein of Hsp70. In summary, using NBC1, an inhibitor of necroptosis, we identified Hsp70 as a molecular chaperone performing dual functions in necroptosis. It stabilizes MLKL protein under normal condition and promotes MLKL polymerization through its substrate-binding domain during necroptosis.
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  • 53
    Publication Date: 2020-02-04
    Description: Developing B cells can be positively or negatively selected by self-antigens, but the mechanisms that determine these outcomes are incompletely understood. Here, we show that a B cell intrinsic switch between positive and negative selection during ontogeny is determined by a change from Lin28b to let-7 gene expression. Ectopic expression of a Lin28b transgene in murine B cells restored the positive selection of autoreactive B-1 B cells by self-antigen in adult bone marrow. Analysis of antigen-specific immature B cells in early and late ontogeny identified Lin28b-dependent genes associated with B-1 B cell development, including Arid3a and Bhleh41, and Lin28b-independent effects are associated with the presence or absence of self-antigen. These findings identify cell intrinsic and extrinsic determinants of B cell fate during ontogeny and reconcile lineage and selection theories of B cell development. They explain how changes in the balance of positive and negative selection may be able to adapt to meet the immunological needs of an individual during its lifetime.
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  • 54
    Publication Date: 2020-06-29
    Description: Nature has inspired the design of robots in which soft actuators enable tasks such as handling of fragile objects and adapting to unstructured environments. Those tasks are difficult for traditional robots, which predominantly consist of hard components. Electrohydraulic soft actuators are liquid-filled shells that deform upon the application of electric fields; they excel among soft actuators with muscle-like force outputs and actuation strains, and with actuation frequencies above 100 Hz. However, the fundamental physics that governs the dynamics of electrohydraulic soft actuators is unexplored. Here, we study the dynamics of electrohydraulic soft actuators using the Peano-HASEL (hydraulically amplified self-healing electrostatic) actuator as a model system. Using experiments and a scaling analysis, we discover two dynamic regimes: a regime in which viscous dissipation reduces the actuation speed and a regime governed by inertial effects in which high-speed actuation is possible. For each regime, we derive a timescale that describes the influence of geometry, materials system, and applied external loads on the actuation speed. We also derive a model to study the dynamic behavior of Peano-HASEL actuators in both regimes. Although this analysis focuses on the Peano-HASEL actuator, the presented results may readily be generalized to other electrohydraulic actuators. When designed to operate in the inertial regime, electrohydraulic actuators will enable bio-inspired robots with unprecedented speeds of motion.
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  • 55
    Publication Date: 2020-06-29
    Description: Maternal effect senescence—a decline in offspring survival or fertility with maternal age—has been demonstrated in many taxa, including humans. Despite decades of phenotypic studies, questions remain about how maternal effect senescence impacts evolutionary fitness. To understand the influence of maternal effect senescence on population dynamics, fitness, and selection, we developed matrix population models in which individuals are jointly classified by age and maternal age. We fit these models to data from individual-based culture experiments on the aquatic invertebrate,Brachionus manjavacas(Rotifera). By comparing models with and without maternal effects, we found that maternal effect senescence significantly reduces fitness forB. manjavacasand that this decrease arises primarily through reduced fertility, particularly at maternal ages corresponding to peak reproductive output. We also used the models to estimate selection gradients, which measure the strength of selection, in both high growth rate (laboratory) and two simulated low growth rate environments. In all environments, selection gradients on survival and fertility decrease with increasing age. They also decrease with increasing maternal age for late maternal ages, implying that maternal effect senescence can evolve through the same process as in Hamilton’s theory of the evolution of age-related senescence. The models we developed are widely applicable to evaluate the fitness consequences of maternal effect senescence across species with diverse aging and fertility schedule phenotypes.
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  • 56
    Publication Date: 2020-06-29
    Description: Autism spectrum disorder (ASD) is characterized by impaired social interactions and communication. The pathogenesis of ASD is not known, but it involves activation of microglia. We had shown that the peptide neurotensin (NT) is increased in the serum of children with ASD and stimulates cultured adult human microglia to secrete the proinflammatory molecules IL-1β and CXCL8. This process is inhibited by the cytokine IL-37. Another cytokine, IL-38, has been reported to have antiinflammatory actions. In this report, we show that pretreatment of cultured adult human microglia with recombinant IL-38 (aa3-152, 1–100 ng/mL) inhibits (P〈 0.0001) NT-stimulated (10 nM) secretion of IL-1β (at 1 ng/mL) and CXCL8 (at 100 ng/mL). In fact, IL-38 (aa3-152, 1 ng/mL) is more potent than IL-37 (100 ng/mL). Here, we report that pretreatment with IL-38 (100 ng/mL) of embryonic microglia (HMC3), in which secretion of IL-1β was undetectable, inhibits secretion of CXCL8 (P= 0.004). Gene expression of IL-38 and its receptor IL-36R are decreased (P= 0.001 andP= 0.04, respectively) in amygdala from patients with ASD (n= 8) compared to non-ASD controls (n= 8), obtained from the University of Maryland NeuroBioBank. IL-38 is increased (P= 0.03) in the serum of children with ASD. These findings indicate an important role for IL-38 in the inhibition of activation of human microglia, thus supporting its development as a treatment approach for ASD.
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  • 57
    Publication Date: 2020-06-29
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  • 58
    Publication Date: 2020-06-29
    Description: Biomolecules can undergo liquid–liquid phase separation (LLPS), forming dense droplets that are increasingly understood to be important for cellular function. Analogous systems are studied as early-life compartmentalization mechanisms, for applications as protocells, or as drug-delivery vehicles. In many of these situations, interactions between the droplet and enzymatic solutes are important to achieve certain functions. To explore this, we carried out experiments in which a model LLPS system, formed from DNA “nanostar” particles, interacted with a DNA-cleaving restriction enzyme, SmaI, whose activity degraded the droplets, causing them to shrink with time. By controlling adhesion of the DNA droplet to a glass surface, we were able to carry out time-resolved imaging of this “active dissolution” process. We found that the scaling properties of droplet shrinking were sensitive to the proximity to the dissolution (“boiling”) temperature of the dense liquid: For systems far from the boiling point, enzymes acted only on the droplet surface, while systems poised near the boiling point permitted enzyme penetration. This was corroborated by the observation of enzyme-induced vacuole-formation (“bubbling”) events, which can only occur through enzyme internalization, and which occurred only in systems poised near the boiling point. Overall, our results demonstrate a mechanism through which the phase stability of a liquid affects its enzymatic degradation through modulation of enzyme transport properties.
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  • 59
    Publication Date: 2020-06-29
    Description: Chemosensory communication is essential to insect biology, playing indispensable roles during mate-finding, foraging, and oviposition behaviors. These traits are particularly important during speciation, where chemical perception may serve to establish species barriers. However, identifying genes associated with such complex behavioral traits remains a significant challenge. Through a combination of transcriptomic and genomic approaches, we characterize the genetic architecture of chemoperception and the role of chemosensing during speciation for a young species pair ofHeliconiusbutterflies,Heliconius melpomeneandHeliconius cydno. We provide a detailed description of chemosensory gene-expression profiles as they relate to sensory tissue (antennae, legs, and mouthparts), sex (male and female), and life stage (unmated and mated female butterflies). Our results untangle the potential role of chemical communication in establishing barriers during speciation and identify strong candidate genes for mate and host plant choice behaviors. Of the 252 chemosensory genes,HmOBP20(involved in volatile detection) andHmGr56(a putative synephrine-related receptor) emerge as strong candidates for divergence in pheromone detection and host plant discrimination, respectively. These two genes are not physically linked to wing-color pattern loci or other genomic regions associated with visual mate preference. Altogether, our results provide evidence for chemosensory divergence betweenH. melpomeneandH. cydno, two rarely hybridizing butterflies with distinct mate and host plant preferences, a finding that supports a polygenic architecture of species boundaries.
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  • 60
    Publication Date: 2020-06-01
    Description: Encoding activity in the medial temporal lobe, presumably evoked by the presentation of stimuli (postonset activity), is known to predict subsequent memory. However, several independent lines of research suggest that preonset activity also affects subsequent memory. We investigated the role of preonset and postonset single-unit and multiunit activity recorded from epilepsy patients as they completed a continuous recognition task. In this task, words were presented in a continuous series and eventually began to repeat. For each word, the patient’s task was to decide whether it was novel or repeated. We found that preonset spiking activity in the hippocampus (when the word was novel) predicted subsequent memory (when the word was later repeated). Postonset activity during encoding also predicted subsequent memory, but was simply a continuation of preonset activity. The predictive effect of preonset spiking activity was much stronger in the hippocampus than in three other brain regions (amygdala, anterior cingulate, and prefrontal cortex). In addition, preonset and postonset activity around the encoding of novel words did not predict memory performance for novel words (i.e., correctly classifying the word as novel), and preonset and postonset activity around the time of retrieval did not predict memory performance for repeated words (i.e., correctly classifying the word as repeated). Thus, the only predictive effect was between preonset activity (along with its postonset continuation) at the time of encoding and subsequent memory. Taken together, these findings indicate that preonset hippocampal activity does not reflect general arousal/attention but instead reflects what we term “attention to encoding.”
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  • 61
    Publication Date: 2020-06-01
    Description: The Q fever agentCoxiella burnetiiuses a defect in organelle trafficking/intracellular multiplication (Dot/Icm) type 4b secretion system (T4SS) to silence the host innate immune response during infection. By investigatingC. burnetiieffector proteins containing eukaryotic-like domains, here we identify NopA (nucleolar protein A), which displays four regulator of chromosome condensation (RCC) repeats, homologous to those found in the eukaryotic Ras-related nuclear protein (Ran) guanine nucleotide exchange factor (GEF) RCC1. Accordingly, NopA is found associated with the chromatin nuclear fraction of cells and uses the RCC-like domain to interact with Ran. Interestingly, NopA triggers an accumulation of Ran-GTP, which accumulates at nucleoli of transfected or infected cells, thus perturbing the nuclear import of transcription factors of the innate immune signaling pathway. Accordingly, qRT-PCR analysis on a panel of cytokines shows that cells exposed to theC. burnetii nopA::Tn or a Dot/Icm-defectivedotA::Tn mutant strain present a functional innate immune response, as opposed to cells exposed to wild-typeC. burnetiior the correspondingnopAcomplemented strain. Thus, NopA is an important regulator of the innate immune response allowingCoxiellato behave as a stealth pathogen.
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  • 62
    Publication Date: 2020-06-01
    Description: The protooncogene MYC regulates a variety of cellular processes, including proliferation and metabolism. Maintaining MYC at homeostatic levels is critical to normal cell function; overexpression drives many cancers. MYC stability is regulated through phosphorylation: phosphorylation at Thr58 signals degradation while Ser62 phosphorylation leads to its stabilization and functional activation. The bromodomain protein 4 (BRD4) is a transcriptional and epigenetic regulator with intrinsic kinase and histone acetyltransferase (HAT) activities that activates transcription of key protooncogenes, includingMYC. We report that BRD4 phosphorylates MYC at Thr58, leading to MYC ubiquitination and degradation, thereby regulating MYC target genes. Importantly, BRD4 degradation, but not inhibition, results in increased levels of MYC protein. Conversely, MYC inhibits BRD4’s HAT activity, suggesting that MYC regulates its own transcription by limiting BRD4-mediated chromatin remodeling of its locus. The MYC stabilizing kinase, ERK1, regulates MYC levels directly and indirectly by inhibiting BRD4 kinase activity. These findings demonstrate that BRD4 negatively regulates MYC levels, which is counteracted by ERK1 activation.
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  • 63
    Publication Date: 2020-06-01
    Description: We report national scale estimates of CO2emissions from fossil-fuel combustion and cement production in the United States based directly on atmospheric observations, using a dual-tracer inverse modeling framework and CO2andΔ14CO2measurements obtained primarily from the North American portion of the National Oceanic and Atmospheric Administration’s Global Greenhouse Gas Reference Network. The derived US national total for 2010 is 1,653 ± 30 TgC yr−1with an uncertainty (1σ) that takes into account random errors associated with atmospheric transport, atmospheric measurements, and specified prior CO2and14C fluxes. The atmosphere-derived estimate is significantly larger (〉3σ) than US national emissions for 2010 from three global inventories widely used for CO2accounting, even after adjustments for emissions that might be sensed by the atmospheric network, but which are not included in inventory totals. It is also larger (〉2σ) than a similarly adjusted total from the US Environmental Protection Agency (EPA), but overlaps EPA’s reported upper 95% confidence limit. In contrast, the atmosphere-derived estimate is within1σof the adjusted 2010 annual total and nine of 12 adjusted monthly totals aggregated from the latest version of the high-resolution, US-specific “Vulcan” emission data product. Derived emissions appear to be robust to a range of assumed prior emissions and other parameters of the inversion framework. While we cannot rule out a possible bias from assumed prior Net Ecosystem Exchange over North America, we show that this can be overcome with additionalΔ14CO2measurements. These results indicate the strong potential for quantification of US emissions and their multiyear trends from atmospheric observations.
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  • 64
    Publication Date: 2020-06-01
    Description: T cell maturation and activation depend upon T cell receptor (TCR) interactions with a wide variety of antigenic peptides displayed in a given major histocompatibility complex (MHC) context. Complementarity-determining region 3 (CDR3) is the most variable part of the TCRα and -β chains, which govern interactions with peptide–MHC complexes. However, it remains unclear how the CDR3 landscape is shaped by individual MHC context during thymic selection of naïve T cells. We established two mouse strains carrying distinct allelic variants ofH2-Aand analyzed thymic and peripheral production and TCR repertoires of naïve conventional CD4+T (Tconv) and naïve regulatory CD4+T (Treg) cells. Compared with tuberculosis-resistant C57BL/6 (H2-Ab) mice, the tuberculosis-susceptible H2-Ajmice had fewer CD4+T cells of both subsets in the thymus. In the periphery, this deficiency was only apparent for Tconvand was compensated for by peripheral reconstitution for Treg. We show that H2-Ajfavors selection of a narrower and more convergent repertoire with more hydrophobic and strongly interacting amino acid residues in the middle of CDR3α and CDR3β, suggesting more stringent selection against a narrower peptide–MHC-II context. H2-Ajand H2-Abmice have prominent reciprocal differences in CDR3α and CDR3β features, probably reflecting distinct modes of TCR fitting to MHC-II variants. These data reveal the mechanics and extent of how MHC-II shapes the naïve CD4+T cell CDR3 landscape, which essentially defines adaptive response to infections and self-antigens.
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  • 65
    Publication Date: 2020-06-01
    Description: Merkel cell carcinoma (MCC) is a lethal skin cancer that metastasizes rapidly. Few effective treatments are available for patients with metastatic MCC. Poor intratumoral T cell infiltration and activation are major barriers that prevent MCC eradication by the immune system. However, the mechanisms that drive the immunologically restrictive tumor microenvironment remain poorly understood. In this study, we discovered that the innate immune regulator stimulator of IFN genes (STING) is completely silenced in MCCs. To reactivate STING in MCC, we developed an application of a human STING mutant, STINGS162A/G230I/Q266I, which we found to be readily stimulated by a mouse STING agonist, DMXAA. This STING molecule was efficiently delivered to MCC cells via an AAV vector. Introducing STINGS162A/G230I/Q266Iexpression and stimulating its activity by DMXAA in MCC cells reactivates their antitumor inflammatory cytokine/chemokine production. In response to MCC cells with restored STING, cocultured T cells expressing MCPyV-specific T cell receptors (TCRs) show increased cytokine production, migration toward tumor cells, and tumor cell killing. Our study therefore suggests that STING deficiency contributes to the immune suppressive nature of MCCs. More importantly, DMXAA stimulation of STINGS162A/G230I/Q266Icauses robust cell death in MCCs as well as several other STING-silenced cancers. Because tumor antigens and DNA released by dying cancer cells have the potential to amplify innate immune response and activate antitumor adaptive responses, our finding indicates that targeted delivery and activation of STINGS162A/G230I/Q266Iin tumor cells holds great therapeutic promise for the treatment of MCC and many other STING-deficient cancers.
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  • 66
    Publication Date: 2020-05-19
    Description: With very little direct biological data of HIV-1 from before the 1980s, far-reaching evolutionary and epidemiological inferences regarding the long prediscovery phase of this pandemic are based on extrapolations by phylodynamic models of HIV-1 genomic sequences gathered mostly over recent decades. Here, using a very sensitive multiplex RT-PCR assay, we screened 1,645 formalin-fixed paraffin-embedded tissue specimens collected for pathology diagnostics in Central Africa between 1958 and 1966. We report the near-complete viral genome in one HIV-1 positive specimen from Kinshasa, Democratic Republic of Congo (DRC), from 1966 (“DRC66”)—a nonrecombinant sister lineage to subtype C that constitutes the oldest HIV-1 near full-length genome recovered to date. Root-to-tip plots showed the DRC66 sequence is not an outlier as would be expected if dating estimates from more recent genomes were systematically biased; and inclusion of the DRC66 sequence in tip-dated BEAST analyses did not significantly alter root and internal node age estimates based on post-1978 HIV-1 sequences. There was larger variation in divergence time estimates among datasets that were subsamples of the available HIV-1 genomes from 1978 to 2014, showing the inherent phylogenetic stochasticity across subsets of the real HIV-1 diversity. Our phylogenetic analyses date the origin of the pandemic lineage of HIV-1 to a time period around the turn of the 20th century (1881 to 1918). In conclusion, this unique archival HIV-1 sequence provides direct genomic insight into HIV-1 in 1960s DRC, and, as an ancient-DNA calibrator, it validates our understanding of HIV-1 evolutionary history.
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  • 67
    Publication Date: 2020-05-19
    Description: Genetic factors and socioeconomic status (SES) inequalities play a large role in educational attainment, and both have been associated with variations in brain structure and cognition. However, genetics and SES are correlated, and no prior study has assessed their neural associations independently. Here we used a polygenic score for educational attainment (EduYears-PGS), as well as SES, in a longitudinal study of 551 adolescents to tease apart genetic and environmental associations with brain development and cognition. Subjects received a structural MRI scan at ages 14 and 19. At both time points, they performed three working memory (WM) tasks. SES and EduYears-PGS were correlated (r= 0.27) and had both common and independent associations with brain structure and cognition. Specifically, lower SES was related to less total cortical surface area and lower WM. EduYears-PGS was also related to total cortical surface area, but in addition had a regional association with surface area in the right parietal lobe, a region related to nonverbal cognitive functions, including mathematics, spatial cognition, and WM. SES, but not EduYears-PGS, was related to a change in total cortical surface area from age 14 to 19. This study demonstrates a regional association of EduYears-PGS and the independent prediction of SES with cognitive function and brain development. It suggests that the SES inequalities, in particular parental education, are related to global aspects of cortical development, and exert a persistent influence on brain development during adolescence.
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  • 68
    Publication Date: 2020-06-08
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  • 69
    Publication Date: 2020-05-18
    Description: Life emerged on Earth within the first quintile of its habitable window, but a technological civilization did not blossom until its last. Efforts to infer the rate of abiogenesis, based on its early emergence, are frustrated by the selection effect that if the evolution of intelligence is a slow process, then life’s early start may simply be a prerequisite to our existence, rather than useful evidence for optimism. In this work, we interpret the chronology of these two events in a Bayesian framework, extending upon previous work by considering that the evolutionary timescale is itself an unknown that needs to be jointly inferred, rather than fiducially set. We further adopt an objective Bayesian approach, such that our results would be agreed upon even by those using wildly different priors for the rates of abiogenesis and evolution—common points of contention for this problem. It is then shown that the earliest microfossil evidence for life indicates that the rate of abiogenesis is at least 2.8 times more likely to be a typically rapid process, rather than a slow one. This modest limiting Bayes factor rises to 8.7 if we accept the more disputed evidence of13C-depleted zircon deposits [E. A. Bell, P. Boehnke, T. M. Harrison, W. L. Mao,Proc. Natl. Acad. Sci. U.S.A.112, 14518–14521 (2015)]. For intelligence evolution, it is found that a rare-intelligence scenario is slightly favored at 3:2 betting odds. Thus, if we reran Earth’s clock, one should statistically favor life to frequently reemerge, but intelligence may not be as inevitable.
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  • 70
    Publication Date: 2020-05-27
    Description: Networks of branched actin filaments formed by Arp2/3 complex generate and experience mechanical forces during essential cellular functions, including cell motility and endocytosis. External forces regulate the assembly and architecture of branched actin networks both in vitro and in cells. Considerably less is known about how mechanical forces influence the disassembly of actin filament networks, specifically, the dissociation of branches. We used microfluidics to apply force to branches formed from purified muscle actin and fission yeast Arp2/3 complex and observed debranching events in real time with total internal reflection fluorescence microscopy. Low forces in the range of 0 pN to 2 pN on branches accelerated their dissociation from mother filaments more than two orders of magnitude, from hours to
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  • 71
    Publication Date: 2020-05-28
    Description: Exploiting bacteriophage-derived homologous recombination processes has enabled precise, multiplex editing of microbial genomes and the construction of billions of customized genetic variants in a single day. The techniques that enable this, multiplex automated genome engineering (MAGE) and directed evolution with random genomic mutations (DIvERGE), are however, currently limited to a handful of microorganisms for which single-stranded DNA-annealing proteins (SSAPs) that promote efficient recombineering have been identified. Thus, to enable genome-scale engineering in new hosts, efficient SSAPs must first be found. Here we introduce a high-throughput method for SSAP discovery that we call “serial enrichment for efficient recombineering” (SEER). By performing SEER inEscherichia colito screen hundreds of putative SSAPs, we identify highly active variants PapRecT and CspRecT. CspRecT increases the efficiency of single-locus editing to as high as 50% and improves multiplex editing by 5- to 10-fold inE. coli, while PapRecT enables efficient recombineering inPseudomonas aeruginosa, a concerning human pathogen. CspRecT and PapRecT are also active in other, clinically and biotechnologically relevant enterobacteria. We envision that the deployment of SEER in new species will pave the way toward pooled interrogation of genotype-to-phenotype relationships in previously intractable bacteria.
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  • 72
    Publication Date: 2020-05-15
    Description: A catalytic prior distribution is designed to stabilize a high-dimensional “working model” by shrinking it toward a “simplified model.” The shrinkage is achieved by supplementing the observed data with a small amount of “synthetic data” generated from a predictive distribution under the simpler model. We apply this framework to generalized linear models, where we propose various strategies for the specification of a tuning parameter governing the degree of shrinkage and study resultant theoretical properties. In simulations, the resulting posterior estimation using such a catalytic prior outperforms maximum likelihood estimation from the working model and is generally comparable with or superior to existing competitive methods in terms of frequentist prediction accuracy of point estimation and coverage accuracy of interval estimation. The catalytic priors have simple interpretations and are easy to formulate.
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  • 73
    Publication Date: 2020-05-14
    Description: Apicomplexan parasites use a specialized cilium structure called the apical complex to organize their secretory organelles and invasion machinery. The apical complex is integrally associated with both the parasite plasma membrane and an intermediate filament cytoskeleton called the inner-membrane complex (IMC). While the apical complex is essential to the parasitic lifestyle, little is known about the regulation of apical complex biogenesis. Here, we identify AC9 (apical cap protein 9), a largely intrinsically disordered component of theToxoplasma gondiiIMC, as essential for apical complex development, and therefore for host cell invasion and egress. Parasites lacking AC9 fail to successfully assemble the tubulin-rich core of their apical complex, called the conoid. We use proximity biotinylation to identify the AC9 interaction network, which includes the kinase extracellular signal-regulated kinase 7 (ERK7). Like AC9, ERK7 is required for apical complex biogenesis. We demonstrate that AC9 directly binds ERK7 through a conserved C-terminal motif and that this interaction is essential for ERK7 localization and function at the apical cap. The crystal structure of the ERK7–AC9 complex reveals that AC9 is not only a scaffold but also inhibits ERK7 through an unusual set of contacts that displaces nucleotide from the kinase active site. ERK7 is an ancient and autoactivating member of the mitogen-activated kinase (MAPK) family and its regulation is poorly understood in all organisms. We propose that AC9 dually regulates ERK7 by scaffolding and concentrating it at its site of action while maintaining it in an “off” state until the specific binding of a true substrate.
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  • 74
    Publication Date: 2020-05-15
    Description: Water wires are critical for the functioning of many membrane proteins, as in channels that conduct water, protons, and other ions. Here, in liquid crystalline lipid bilayers under symmetric environmental conditions, the selective hydrogen bonding interactions between eight waters comprising a water wire and a subset of 26 carbonyl oxygens lining the antiparallel dimeric gramicidin A channel are characterized by17O NMR spectroscopy at 35.2 T (or 1,500 MHz for1H) and computational studies. While backbone15N spectra clearly indicate structural symmetry between the two subunits, single site17O labels of the pore-lining carbonyls report two resonances, implying a break in dimer symmetry caused by the selective interactions with the water wire. The17O shifts document selective water hydrogen bonding with carbonyl oxygens that are stable on the millisecond timescale. Such interactions are supported by density functional theory calculations on snapshots taken from molecular dynamics simulations. Water hydrogen bonding in the pore is restricted to just three simultaneous interactions, unlike bulk water environs. The stability of the water wire orientation and its electric dipole leads to opposite charge-dipole interactions for K+ions bound at the two ends of the pore, thereby providing a simple explanation for an ∼20-fold difference in K+affinity between two binding sites that are ∼24 Å apart. The17O NMR spectroscopy reported here represents a breakthrough in high field NMR technology that will have applications throughout molecular biophysics, because of the acute sensitivity of the17O nucleus to its chemical environment.
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  • 75
    Publication Date: 2020-05-28
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  • 76
    Publication Date: 2020-05-18
    Description: HRAS, NRAS, and KRAS4A/KRAS4B comprise the RAS family of small GTPases that regulate signaling pathways controlling cell proliferation, differentiation, and survival. RAS pathway abnormalities cause developmental disorders and cancers. We found that KRAS4B colocalizes on the cell membrane with other RAS isoforms and a subset of prenylated small GTPase family members using a live-cell quantitative split luciferase complementation assay. RAS protein coclustering is mainly mediated by membrane association-facilitated interactions (MAFIs). Using the RAS–RBD (CRAF RAS binding domain) interaction as a model system, we showed that MAFI alone is not sufficient to induce RBD-mediated RAS inhibition. Surprisingly, we discovered that high-affinity membrane-targeted RAS binding proteins inhibit RAS activity and deplete RAS proteins through an autophagosome–lysosome-mediated degradation pathway. Our results provide a mechanism for regulating RAS activity and protein levels, a more detailed understanding of which should lead to therapeutic strategies for inhibiting and depleting oncogenic RAS proteins.
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  • 77
    Publication Date: 2020-06-01
    Description: The ability to modulate cellular electrophysiology is fundamental to the investigation of development, function, and disease. Currently, there is a need for remote, nongenetic, light-induced control of cellular activity in two-dimensional (2D) and three-dimensional (3D) platforms. Here, we report a breakthrough hybrid nanomaterial for remote, nongenetic, photothermal stimulation of 2D and 3D neural cellular systems. We combine one-dimensional (1D) nanowires (NWs) and 2D graphene flakes grown out-of-plane for highly controlled photothermal stimulation at subcellular precision without the need for genetic modification, with laser energies lower than a hundred nanojoules, one to two orders of magnitude lower than Au-, C-, and Si-based nanomaterials. Photothermal stimulation using NW-templated 3D fuzzy graphene (NT-3DFG) is flexible due to its broadband absorption and does not generate cellular stress. Therefore, it serves as a powerful toolset for studies of cell signaling within and between tissues and can enable therapeutic interventions.
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  • 78
    Publication Date: 2020-06-02
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  • 79
    Publication Date: 2020-05-18
    Description: The androgen receptor (AR) antagonist enzalutamide is one of the principal treatments for men with castration-resistant prostate cancer (CRPC). However, not all patients respond, and resistance mechanisms are largely unknown. We hypothesized that genomic and transcriptional features from metastatic CRPC biopsies prior to treatment would be predictive of de novo treatment resistance. To this end, we conducted a phase II trial of enzalutamide treatment (160 mg/d) in 36 men with metastatic CRPC. Thirty-four patients were evaluable for the primary end point of a prostate-specific antigen (PSA)50 response (PSA decline ≥50% at 12 wk vs. baseline). Nine patients were classified as nonresponders (PSA decline
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  • 80
    Publication Date: 2020-05-18
    Description: Plant cuticles are composed of wax and cutin and evolved in the land plants as a hydrophobic boundary that reduces water loss from the plant epidermis. The expanding maize adult leaf displays a dynamic, proximodistal gradient of cuticle development, from the leaf base to the tip. Laser microdissection RNA Sequencing (LM-RNAseq) was performed along this proximodistal gradient, and complementary network analyses identified potential regulators of cuticle biosynthesis and deposition. A weighted gene coexpression network (WGCN) analysis suggested a previously undescribed function for PHYTOCHROME-mediated light signaling during the regulation of cuticular wax deposition. Genetic analyses reveal thatphyB1 phyB2double mutants of maize exhibit abnormal cuticle composition, supporting the predictions of our coexpression analysis. Reverse genetic analyses also show thatphymutants of the mossPhyscomitrella patensexhibit abnormal cuticle composition, suggesting an ancestral role for PHYTOCHROME-mediated, light-stimulated regulation of cuticle development during plant evolution.
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  • 81
    Publication Date: 2020-05-14
    Description: In multiple sclerosis (MS), Th17 cells are critical drivers of autoimmune central nervous system (CNS) inflammation and demyelination. Th17 cells exhibit functional heterogeneity fostering both pathogenic and nonpathogenic, tissue-protective functions. Still, the factors that control Th17 pathogenicity remain incompletely defined. Here, using experimental autoimmune encephalomyelitis, an established mouse MS model, we report that therapeutic administration of activin-A ameliorates disease severity and alleviates CNS immunopathology and demyelination, associated with decreased activation of Th17 cells. In fact, activin-A signaling through activin-like kinase-4 receptor represses pathogenic transcriptional programs in Th17-polarized cells, while it enhances antiinflammatory gene modules. Whole-genome profiling and in vivo functional studies revealed that activation of the ATP-depleting CD39 and CD73 ectonucleotidases is essential for activin-A–induced suppression of the pathogenic signature and the encephalitogenic functions of Th17 cells. Mechanistically, the aryl hydrocarbon receptor, along with STAT3 and c-Maf, are recruited to promoter elements onEntpd1andNt5e(encoding CD39 and CD73, respectively) and other antiinflammatory genes, and control their expression in Th17 cells in response to activin-A. Notably, we show that activin-A negatively regulates the metabolic sensor, hypoxia-inducible factor-1α, and key inflammatory proteins linked to pathogenic Th17 cell states. Of translational relevance, we demonstrate that activin-A is induced in the CNS of individuals with MS and restrains human Th17 cell responses. These findings uncover activin-A as a critical controller of Th17 cell pathogenicity that can be targeted for the suppression of autoimmune CNS inflammation.
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  • 82
    Publication Date: 2020-06-01
    Description: The Hippo pathway plays a pivotal role in tissue homeostasis and tumor suppression. YAP and TAZ are downstream effectors of the Hippo pathway, and their activities are tightly suppressed by phosphorylation-dependent cytoplasmic retention. However, the molecular mechanisms governing YAP/TAZ nuclear localization have not been fully elucidated. Here, we report that Mastermind-like 1 and 2 (MAML1/2) are indispensable for YAP/TAZ nuclear localization and transcriptional activities. Ectopic expression or depletion of MAML1/2 induces nuclear translocation or cytoplasmic retention of YAP/TAZ, respectively. Additionally, mutation of the MAML nuclear localization signal, as well as its YAP/TAZ interacting region, both abolish nuclear localization and transcriptional activity of YAP/TAZ. Importantly, we demonstrate that the level ofMAML1messenger RNA (mRNA) is regulated by microRNA-30c (miR-30c) in a cell-density-dependent manner. In vivo and clinical results suggest that MAML potentiates YAP/TAZ oncogenic function and positively correlates with YAP/TAZ activation in human cancer patients, suggesting pathological relevance in the context of cancer development. Overall, our study not only provides mechanistic insight into the regulation of YAP/TAZ subcellular localization, but it also strongly suggests that the miR30c–MAML–YAP/TAZ axis is a potential therapeutic target for developing novel cancer treatments.
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  • 83
    Publication Date: 2020-05-27
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  • 84
    Publication Date: 2020-05-29
    Description: The Pioneer 100 Wellness Project involved quantitatively profiling 108 participants’ molecular physiology over time, including genomes, gut microbiomes, blood metabolomes, blood proteomes, clinical chemistries, and data from wearable devices. Here, we present a longitudinal analysis focused specifically around the Pioneer 100 gut microbiomes. We distinguished a subpopulation of individuals with reduced gut diversity, elevated relative abundance of the genusPrevotella, and reduced levels of the genusBacteroides. We found that the relative abundances ofBacteroidesandPrevotellawere significantly correlated with certain serum metabolites, including omega-6 fatty acids. Primary dimensions in distance-based redundancy analysis of clinical chemistries explained 18.5% of the variance in bacterial community composition, and revealed aBacteroides/Prevotelladichotomy aligned with inflammation and dietary markers. Finally, longitudinal analysis of gut microbiome dynamics within individuals showed that direct transitions betweenBacteroides-dominated andPrevotella-dominated communities were rare, suggesting the presence of a barrier between these states. One implication is that interventions seeking to transition betweenBacteroides- andPrevotella-dominated communities will need to identify permissible paths through ecological state-space that circumvent this apparent barrier.
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  • 85
    Publication Date: 2020-05-19
    Description: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a dismal prognosis. Currently, there is no effective therapy for PDAC, and a detailed molecular and functional evaluation of PDACs is needed to identify and develop better therapeutic strategies. Here we show that the transcription factor Krüppel-like factor 7 (KLF7) is overexpressed in PDACs, and that inhibition of KLF7 blocks PDAC tumor growth and metastasis in cell culture and in mice. KLF7 expression in PDACs can be up-regulated due to activation of a MAP kinase pathway or inactivation of the tumor suppressor p53, two alterations that occur in a large majority of PDACs. ShRNA-mediated knockdown of KLF7 inhibits the expression of IFN-stimulated genes (ISGs), which are necessary for KLF7-mediated PDAC tumor growth and metastasis. KLF7 knockdown also results in the down-regulation of Discs Large MAGUK Scaffold Protein 3 (DLG3), resulting in Golgi complex fragmentation, and reduced protein glycosylation, leading to reduced secretion of cancer-promoting growth factors, such as chemokines. Genetic or pharmacologic activation of Golgi complex fragmentation blocks PDAC growth and metastasis similar to KLF7 inhibition. Our results demonstrate a therapeutically amenable, KLF7-driven pathway that promotes PDAC growth and metastasis by activating ISGs and maintaining Golgi complex integrity.
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  • 86
    Publication Date: 2020-05-27
    Description: Two-dimensional (2D) molybdenum disulfide (MoS2) nanomaterials are an emerging class of biomaterials that are photoresponsive at near-infrared wavelengths (NIR). Here, we demonstrate the ability of 2D MoS2to modulate cellular functions of human stem cells through photothermal mechanisms. The interaction of MoS2and NIR stimulation of MoS2with human stem cells is investigated using whole-transcriptome sequencing (RNA-seq). Global gene expression profile of stem cells reveals significant influence of MoS2and NIR stimulation of MoS2on integrins, cellular migration, and wound healing. The combination of MoS2and NIR light may provide new approaches to regulate and direct these cellular functions for the purposes of regenerative medicine as well as cancer therapy.
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  • 87
    Publication Date: 2020-05-18
    Description: Spin Hall effect (SHE), a mechanism by which materials convert achargecurrent into aspincurrent, invokes interesting physics and promises to empower transformative, energy-efficient memory technology. However, fundamental questions remain about the essential factors that determine SHE. Here, we solve this open problem, presenting a comprehensive theory of five rational design principles for achievinggiantintrinsic SHE in transition metal oxides. Arising from our key insight regarding the inherently geometric nature of SHE, we demonstrate that two of these design principles are weak crystal fields and the presence of structural distortions. Moreover, we discover that antiperovskites are a highly promising class of materials for achieving giant SHE, reaching SHE values anorder of magnitudelarger than that reported for any oxide. Additionally, we derive three other design principles for enhancing SHE. Our findings bring deeper insight into the physics driving SHE and could help enhance and externally control SHE values.
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  • 88
    Publication Date: 2020-05-18
    Description: Split inteins are privileged molecular scaffolds for the chemical modification of proteins. Though efficient for in vitro applications, these polypeptide ligases have not been utilized for the semisynthesis of proteins in live cells. Here, we biochemically and structurally characterize the naturally split intein VidaL. We show that this split intein, which features the shortest known N-terminal fragment, supports rapid and efficient proteintrans-splicing under a range of conditions, enabling semisynthesis of modified proteins both in vitro and in mammalian cells. The utility of this protein engineering system is illustrated through the traceless assembly of multidomain proteins whose biophysical properties render them incompatible with a single expression system, as well as by the semisynthesis of dual posttranslationally modified histone proteins in live cells. We also exploit the domain swapping function of VidaL to effect simultaneous modification and translocation of the nuclear protein HP1α in live cells. Collectively, our studies highlight the VidaL system as a tool for the precise chemical modification of cellular proteins with spatial and temporal control.
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  • 89
    Publication Date: 2020-05-19
    Description: Lesch-Nyhan disease (LND), caused by a deficient salvage purine pathway, is characterized by severe neurological manifestations and uric acid overproduction. However, uric acid is not responsible for brain dysfunction, and it has been suggested that purine nucleotide depletion, or accumulation of other toxic purine intermediates, could be more relevant. Here we show that purine alterations in LND fibroblasts depend on the level of folic acid in the culture media. Thus, physiological levels of folic acid induce accumulation of 5-aminoimidazole-4-carboxamide riboside 5′-monophosphate (ZMP), an intermediary of de novo purine biosynthetic pathway, and depletion of ATP. Additionally, Z-nucleotide derivatives (AICAr, AICA) are detected at high levels in the urine of patients with LND and its variants (hypoxanthine-guanine phosphoribosyltransferase [HGprt]-related neurological dysfunction and HGprt-related hyperuricemia), and the ratio of AICAr/AICA is significantly increased in patients with neurological problems (LND and HGprt-related neurological dysfunction). Moreover, AICAr is present in the cerebrospinal fluid of patients with LND, but not in control individuals. We hypothesize that purine alterations detected in LND fibroblasts may also occur in the brain of patients with LND.
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  • 90
    Publication Date: 2020-05-19
    Description: PD-1 and PD-L1 act to restrict T cell responses in cancer and contribute to self-tolerance. Consistent with this role, PD-1 checkpoint inhibitors have been associated with immune-related adverse events (irAEs), immune toxicities thought to be autoimmune in origin. Analyses of dermatological irAEs have identified an association with improved overall survival (OS) following anti–PD-(L)1 therapy, but the factors that contribute to this relationship are poorly understood. We collected germline whole-genome sequencing data from IMvigor211, a recent phase 3 randomized controlled trial comparing atezolizumab (anti–PD-L1) monotherapy to chemotherapy in bladder cancer. We found that high vitiligo, high psoriasis, and low atopic dermatitis polygenic risk scores (PRSs) were associated with longer OS under anti–PD-L1 monotherapy as compared to chemotherapy, reflecting the Th17 polarization of these diseases. PRSs were not correlated with tumor mutation burden, PD-L1 immunohistochemistry, nor T-effector gene signatures. Shared genetic factors impact risk for dermatological autoimmunity and anti–PD-L1 monotherapy in bladder cancer.
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  • 91
    Publication Date: 2020-05-19
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  • 92
    Publication Date: 2020-05-19
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  • 93
    Publication Date: 2020-05-20
    Description: Synthetic chemical elicitors, so called plant strengtheners, can protect plants from pests and pathogens. Most plant strengtheners act by modifying defense signaling pathways, and little is known about other mechanisms by which they may increase plant resistance. Moreover, whether plant strengtheners that enhance insect resistance actually enhance crop yields is often unclear. Here, we uncover how a mechanism by which 4-fluorophenoxyacetic acid (4-FPA) protects cereals from piercing-sucking insects and thereby increases rice yield in the field. Four-FPA does not stimulate hormonal signaling, but modulates the production of peroxidases, H2O2, and flavonoids and directly triggers the formation of flavonoid polymers. The increased deposition of phenolic polymers in rice parenchyma cells of 4-FPA-treated plants is associated with a decreased capacity of the white-backed planthopper (WBPH)Sogatella furciferato reach the plant phloem. We demonstrate that application of 4-PFA in the field enhances rice yield by reducing the abundance of, and damage caused by, insect pests. We demonstrate that 4-FPA also increases the resistance of other major cereals such as wheat and barley to piercing-sucking insect pests. This study unravels a mode of action by which plant strengtheners can suppress herbivores and increase crop yield. We postulate that this represents a conserved defense mechanism of plants against piercing-sucking insect pests, at least in cereals.
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  • 94
    Publication Date: 2020-05-18
    Description: The mechanisms that regulate germinal center (GC) B cell responses in the spleen are not fully understood. Here we use a combination of pharmacologic and genetic approaches to delete SIGN-R1+marginal zone (MZ) macrophages and reveal their specific contribution to the regulation of humoral immunity in the spleen. We find that while SIGN-R1+macrophages were not essential for initial activation of B cells, they were required for maturation of the response and development of GC B cells. These defects could be corrected when follicular helper T (Tfh) cells were induced before macrophage ablation or when Tfh responses were enhanced. Moreover, we show that in the absence of SIGN-R1+macrophages, DCIR2+dendritic cells (DCs), which play a key role in priming Tfh responses, were unable to cluster to the interfollicular regions of the spleen and were instead displaced to the MZ. Restoring SIGN-R1+macrophages to the spleen corrected positioning of DCIR2+DCs and rescued the GC B cell response. Our study reveals a previously unappreciated role for SIGN-R1+macrophages in regulation of the GC reaction and highlights the functional specification of macrophage subsets in the MZ compartment.
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  • 95
    Publication Date: 2020-05-11
    Description: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two related neurodegenerative diseases that present with similar TDP-43 pathology in patient tissue. TDP-43 is an RNA-binding protein which forms aggregates in neurons of ALS and FTD patients as well as in a subset of patients diagnosed with other neurodegenerative diseases. Despite our understanding that TDP-43 is essential for many aspects of RNA metabolism, it remains obscure how TDP-43 dysfunction contributes to neurodegeneration. Interestingly, altered neuronal dendritic morphology is a common theme among several neurological disorders and is thought to precede neurodegeneration. We previously found that both TDP-43 overexpression (OE) and knockdown (KD) result in reduced dendritic branching of cortical neurons. In this study, we used TRIBE (targets of RNA-binding proteins identified by editing) as an approach to identify signaling pathways that regulate dendritic branching downstream of TDP-43. We found that TDP-43 RNA targets are enriched for pathways that signal to the CREB transcription factor. We further found that TDP-43 dysfunction inhibits CREB activation and CREB transcriptional output, and restoring CREB signaling rescues defects in dendritic branching. Finally, we demonstrate, using RNA sequencing, that TDP-43 OE and KD cause similar changes in the abundance of specific messenger RNAs, consistent with their ability to produce similar morphological defects. Our data therefore provide a mechanism by which TDP-43 dysfunction interferes with dendritic branching, and may define pathways for therapeutic intervention in neurodegenerative diseases.
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  • 96
    Publication Date: 2020-02-03
    Description: Exposure to loud sound damages the postsynaptic terminals of spiral ganglion neurons (SGNs) on cochlear inner hair cells (IHCs), resulting in loss of synapses, a process termed synaptopathy. Glutamatergic neurotransmission via α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type receptors is required for synaptopathy, and here we identify a possible involvement of GluA2-lacking Ca2+-permeable AMPA receptors (CP-AMPARs) using IEM-1460, which has been shown to block GluA2-lacking AMPARs. In CBA/CaJ mice, a 2-h exposure to 100-dB sound pressure level octave band (8 to 16 kHz) noise results in no permanent threshold shift but does cause significant synaptopathy and a reduction in auditory brainstem response (ABR) wave-I amplitude. Chronic intracochlear perfusion of IEM-1460 in artificial perilymph (AP) into adult CBA/CaJ mice prevented the decrease in ABR wave-I amplitude and the synaptopathy relative to intracochlear perfusion of AP alone. Interestingly, IEM-1460 itself did not affect the ABR threshold, presumably because GluA2-containing AMPARs can sustain sufficient synaptic transmission to evoke low-threshold responses during blockade of GluA2-lacking AMPARs. On individual postsynaptic densities, we observed GluA2-lacking nanodomains alongside regions with robust GluA2 expression, consistent with the idea that individual synapses have both CP-AMPARs and Ca2+-impermeable AMPARs. SGNs innervating the same IHC differ in their relative vulnerability to noise. We found local heterogeneity among synapses in the relative abundance of GluA2 subunits that may underlie such differences in vulnerability. We propose a role for GluA2-lacking CP-AMPARs in noise-induced cochlear synaptopathy whereby differences among synapses account for differences in excitotoxic susceptibility. These data suggest a means of maintaining normal hearing thresholds while protecting against noise-induced synaptopathy, via selective blockade of CP-AMPARs.
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  • 97
    Publication Date: 2020-01-24
    Description: Obesity is associated with a chronic state of low-grade inflammation and progressive tissue infiltration by immune cells and increased expression of inflammatory cytokines. It is established that interleukin 6 (IL6) regulates multiple aspects of metabolism, including glucose disposal, lipolysis, oxidative metabolism, and energy expenditure. IL6 is secreted by many tissues, but the role of individual cell types is unclear. We tested the role of specific cells using a mouse model with conditional expression of the Il6 gene. We found that IL6 derived from adipocytes increased, while IL6 derived from myeloid cells and muscle suppressed, macrophage infiltration of adipose tissue. These opposite actions were associated with a switch of IL6 signaling from a canonical mode (myeloid cells) to a noncanonical trans-signaling mode (adipocytes and muscle) with increased expression of the ADAM10/17 metalloprotease that promotes trans-signaling by the soluble IL6 receptor α. Collectively, these data demonstrate that the source of IL6 production plays a major role in the physiological regulation of metabolism.
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  • 98
    Publication Date: 2020-02-10
    Description: Lung cancer is the leading cause of cancer-related deaths worldwide and non-small cell lung cancer (NSCLC) accounts for over 80% of lung cancer cases. The RNA binding protein, QKI, belongs to the STAR family and plays tumor-suppressive functions in NSCLC. QKI-5 is a major isoform of QKIs and is predominantly expressed in NSCLC. However, the underlying mechanisms of QKI-5 in NSCLC progression remain unclear. We found that QKI-5 regulated microRNA (miRNA), miR-196b-5p, and its expression was significantly up-regulated in NSCLC tissues. Up-regulated miR-196b-5p promotes lung cancer cell migration, proliferation, and cell cycle through directly targeting the tumor suppressors, GATA6 and TSPAN12. Both GATA6 and TSPAN12 expressions were down-regulated in NSCLC patient tissue samples and were negatively correlated with miR-196b-5p expression. Mouse xenograft models demonstrated that miR-196b-5p functions as a potent onco-miRNA, whereas TSPAN12 functions as a tumor suppressor in NSCLC in vivo. QKI-5 bound to miR-196b-5p and influenced its stability, resulting in up-regulated miR-196b-5p expression in NSCLC. Further analysis showed that hypomethylation in the promoter region enhanced miR-196b-5p expression in NSCLC. Our findings indicate that QKI-5 may exhibit novel anticancer mechanisms by regulating miRNA in NSCLC, and targeting the QKI5∼miR-196b-5p∼GATA6/TSPAN12 pathway may enable effectively treating some NSCLCs.
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  • 99
    Publication Date: 2020-05-11
    Description: The neonicotinoid nitenpyram (NPM) is a multifunctional nitroenamine [(R1N)(R2N)C=CHNO2] pesticide. As a nitroalkene, it is structurally similar to other emerging contaminants such as the pharmaceuticals ranitidine and nizatidine. Because ozone is a common atmospheric oxidant, such compounds may be oxidized on contact with air to form new products that have different toxicity compared to the parent compounds. Here we show that oxidation of thin solid films of NPM by gas-phase ozone produces unexpected products, the majority of which do not contain oxygen, despite the highly oxidizing reactant. A further surprising finding is the formation of gas-phase nitrous acid (HONO), a species known to be a major photolytic source of the highly reactive hydroxyl radical in air. The results of application of a kinetic multilayer model show that reaction was not restricted to the surface layers but, at sufficiently high ozone concentrations, occurred throughout the film. The rate constant derived for the O3−NPM reaction is 1 × 10−18cm3⋅s−1, and the diffusion coefficient of ozone in the thin film is 9 × 10−10cm2⋅s−1. These findings highlight the unique chemistry of multifunctional nitroenamines and demonstrate that known chemical mechanisms for individual moieties in such compounds cannot be extrapolated from simple alkenes. This is critical for guiding assessments of the environmental fates and impacts of pesticides and pharmaceuticals, and for providing guidance in designing better future alternatives.
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  • 100
    Publication Date: 2020-05-11
    Description: Human T cell leukemia virus 1 (HTLV-1) causes the functionally debilitating disease HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP) as well as adult T cell leukemia lymphoma (ATLL). Although there were concerns that the mortality of HAM/TSP could be affected by the development of ATLL, prospective evidence was lacking in this area. In this 5-y prospective cohort study, we determined the mortality, prevalence, and incidence of ATLL in 527 HAM/TSP patients. The standard mortality ratio of HAM/TSP patients was 2.25, and ATLL was one of the major causes of death (5/33 deaths). ATLL prevalence and incidence in these patients were 3.0% and 3.81 per 1,000 person-y, respectively. To identify patients at a high risk of developing ATLL, flow cytometry, Southern blotting, and targeted sequencing data were analyzed in a separate cohort of 218 HAM/TSP patients. In 17% of the HAM/TSP patients, we identified an increase in T cells positive for cell adhesion molecule 1 (CADM1), a marker for ATLL and HTLV-1–infected cells. Genomic analysis revealed that somatic mutations of HTLV-1–infected cells were seen in 90% of these cases and 11% of them had dominant clone and developed ATLL in the longitudinal observation. In this study, we were able to demonstrate the increased mortality in patients with HAM/TSP and a significant effect of ATLL on their prognosis. Having dominant clonal expansion of HTLV-1–infected cells with ATLL-associated somatic mutations may be important characteristics of patients with HAM/TSP who are at an increased risk of developing ATLL.
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