bluuebunny/crossref_metadata_2025 huggingface dataset:
Borderline-Persönlichkeitsstörungen
Authors: Kaess Michael , Herpertz Sabine C. , Plener Paul L. , Schmahl Christian
Published: November 2019

Zusammenfassung. Im Rahmen der Task-Force Transitionspsychiatrie der Deutschen Gesellschaft für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie e. V. (DGKJP) und der Deutschen Gesellschaft für Psychiatrie und Psychotherapie, Psychosomatik und Nervenheilkunde (DGPPN) wurde die Bedeutung der Lebensphase der Adoleszenz für die Versorgung von Borderline-Persönlichkeitsstörungen (BPS) in Deutschland durch eine Gruppe von Expertinnen und Experten näher beleuchtet. Besondere Lücken und Probleme wurden in den folgenden Bereichen identifiziert: Früherkennung der BPS; Zugang zu spezifischer, ambulanter Psychotherapie; langwierige, stationäre Behandlungen und Polypharmazie. Die Autorinnen und Autoren beschreiben in der Folge einige Empfehlungen und Forderungen betreffend der Generierung und Dissemination von Wissen zur BPS bei Adoleszenten sowie zu möglichen Anpassungen im deutschen Gesundheitssystem.
Lightning NOx Production in the Tropics as Determined Using OMI NO2 Retrievals and WWLLN Stroke Data
Authors: Allen Dale J. , Pickering Kenneth E. , Bucsela Eric , Krotkov Nickolay , Holzworth Robert
Published: November 2019

Nitrogen oxide (NOx) production by lightning in the tropics is estimated using tropospheric NOx amounts (LNOx*) over deep convective grid boxes derived from Ozone Monitoring Instrument (OMI) nitrogen dioxide (NO2) slant columns and detection‐efficiency–adjusted World Wide Lightning Location Network (WWLLN) flashes. The lightning NOx production efficiency (LNOx PE) in the tropics is determined for the austral and boreal summers of 2007 to 2011 by regressing regional mean daily values of LNOx* for individual seasons against daily flash totals during flash windows prior to the OMI overpass. LNOx PE is determined to be approximately two times larger over marine locations than over continental locations possibly because marine flashes are more energetic. Overall, the mean LNOx PE for the tropics is calculated to be 170 ± 100 mol per flash with values over the tropical Pacific (low flash rate region) being largest. The main contributors to uncertainties in PE are uncertainties in WWLLN flash detection efficiency, upper tropospheric NOx lifetime in the near field of convection, and air mass factor biases.
Effects of Air‐Sea Interaction on the Eyewall Replacement Cycle of Typhoon Sinlaku (2008): Verification of Numerical Simulation
Authors: Yang Lu , Cheng Xiaoping , Huang Xiaogang , Fei Jianfang , Li Xiangcheng
Published: November 2019

To explore the effects of air‐sea interaction on the eyewall replacement cycle (ERC) of tropical cyclones (TCs), an ERC of Typhoon Sinlaku (2008) was reproduced using the high‐resolution coupled ocean‐atmosphere‐wave‐sediment transport (COAWST) model. The numerical simulations were evaluated with a wide range of observational datasets. Moreover, the importance of the ocean to ERC is discussed by comparing six sensitive experiments, that is, three uncoupled experiments with different time‐invariant sea surface temperatures, an ocean‐atmosphere coupled experiment, an ocean‐wave coupled experiment, and an ocean‐atmosphere‐wave fully coupled experiment. The results show that Sinlaku simulated by the fully coupled experiment was highly consistent with the observations, and the evolution of ERC varies from those only simulated by the atmospheric models in previous studies. When the ocean and waves were both considered, the lifetime of the ERC was significantly prolonged, even though the simulated Sinlaku was weakened by the cooling of the sea; the asymmetric distribution of the concentric eyewalls (CEs) which caused by the non‐uniform energy exchanges was also prominent. By contrast, without ocean coupling, the simulated secondary eyewall, composed of axisymmetric convections, exhibited false enhancement and fake inward contraction, and the duration of the ERC was also shorter than that actually observed. In conclusion, the results highlight the significance of ocean coupling for the numerical simulation of the ERC of a TC, including survival time and asymmetric structure.
Comprehensive Evaluation of Satellite‐Based Precipitation at Sub‐Daily Time Scales Over a High‐Profile Watershed with Complex Terrain
Authors: Liu Shuang , Hu Kaiheng , Zhang Shaojie , Zeng Yujin
Published: November 2019

In this study, a preliminary quantitative evaluation of global precipitation measurement (GPM) mission precipitation products at sub‐daily time scales was performed in a typical and small watershed with complex terrain in southwestern China. The world heritage Jiuzhaigou Valley, which has been affected by many rainfall‐triggered debris‐flow disasters after the Ms 7.0 earthquake on 8 August 2017, was selected as the study area. The “early”, “late” and “final” half‐hourly GPM precipitations and hourly observations by four rainfall stations were used, and various indicators (general statistical indices, classification indicators, and a joint probability distribution function) were adopted as metrics to evaluate the GPM rainfall. Results indicated that the early and late hourly products showed a medium degree of correlation with ground observations, while the final hourly product showed better performances and may be used for research‐level applications in the study area. GPM products could approximately reproduce the diurnal cycles of observed precipitation whereas the relationship between peak rainfall and duration spell was in good agreement with ground observations. The 1‐hour final product was unable to significantly reduce the rate of missing report for rain although it was calibrated by global monthly data. An event‐based evaluation showed that the GPM performed well for the cumulative rainfall. The assessment results support the development of early‐warning models for rainfall‐triggered geological disasters, provide useful implications on the improvement of rainfall retrieval algorithm in complex mountainous areas, and may be used as reference for scientific studies in poorly sampled regions with similar geographical conditions as the Jiuzhaigou Valley.
A Full Satellite‐Driven Method for the Retrieval of Clear‐Sky Evapotranspiration
Authors: Leng Pei , Liao Qian‐Yu , Gao Mao‐Fang , Duan Si‐Bo , Li Zhao‐Liang , Zhang Xia , Shang Guo‐Fei
Published: November 2019

Evapotranspiration (ET) plays an important role in the soil‐vegetation‐atmosphere system for its considerable effect in surface energy balance and water cycle. The determination of ET based on full satellite data has been a challenge. In the present study, a full satellite‐driven method is proposed based on a newly developed pixel‐to‐pixel scheme of the land surface temperature‐vegetation index trapezoidal feature space in the presence of clear‐sky conditions. For the implementation of this approach, the three main meteorological parameters of net surface radiation, air temperature, and relative humidity were obtained solely based on satellite observations. With the exception of the three main satellite‐derived meteorological parameters, different wind speed data—including actual measurements, the assimilated product, and an averaged value of meteorological observations—were used to investigate their effects on the retrieval of ET. Specifically, two pixel‐to‐pixel trapezoidal feature space schemes, namely an original and a two‐stage scheme, were implemented to estimate ET over an arid region of the study area located in the northwest part of China. Comparison of the estimated ET with the values acquired from the eddy covariance systems yielded a reliable accuracy response with root‐mean‐squared errors of ~80 W/m2 and ~70 W/m2 for the original and two‐stage trapezoidal methods with satellite‐derived inputs, respectively, and constant wind speed data over the growing 2012 season from May to September. These results indicate that the full satellite‐driven method is capable of estimating ET over the arid region of the study area.
Giving Thanks to Geosci
Authors:   AGU
Published: November 2019

What facets of Earth and space science are we grateful for this week?
Constraining the Intracontinental Tectonics of the SW Central Asian Orogenic Belt by the Early Permian Paleomagnetic Pole for the Turfan‐Hami Block
Authors: Zhu Xin , Wang Bo , Chen Yan , Liu Hongsheng
Published: November 2019

In order to better understand the kinematics and geodynamics of the late Paleozoic to early Mesozoic transition from accretionary to intracontinental tectonics in the southwest Central Asian Orogenic Belt, we performed a paleomagnetic study on Lower Permian strata in the Turpan‐Hami Basin, NW China. Magnetite and hematite are shown to be the principal magnetic remanence carriers. A typical sedimentary fabric that has not been modified by postdepositional deformation is recognized via magnetic fabric study. Stable characteristic remanent magnetizations, all of reverse magnetic polarity, are revealed by step demagnetizations. Remanence age is determined to be of Early Permian affinity, based on a fold test, remanence behavior of minerals, and geochronologic data. With inclination shallowing corrections, the first Early Permian paleomagnetic pole for the Turpan‐Hami Block is acquired as λ = 75.7°N, φ = 276.3°E, A95 = 5.7°, and N = 10 sites. Comparisons of this new pole with published ones from neighboring cratonic blocks provide kinematic constraints on the tectonic transition and subsequent intracontinental tectonics of this region. The Turpan‐Hami and Yili blocks have kept their relative positions since the Early Permian. Significant latitudinal movement of 14.7° ± 7.2° occurred between the Turpan‐Hami and South Junggar blocks and could be mainly accommodated by late Paleozoic crustal shortening of at least ~530 km across an intra‐arc basin in the Bogda belt. The Turpan‐Hami Block has experienced large‐magnitude relative rotations of −41.1° ± 7.1° and 21.2° ± 9.4° with respect to Tarim and South Junggar since the Early Permian, respectively, corresponding to dominant intracontinental tectonics characterized by large‐magnitude strike‐slip displacements along megashear zones.
A Joint Inversion for Three‐dimensional P and S Wave Velocity Structure and Earthquake Locations Beneath Axial Seamount
Authors: Baillard Christian , Wilcock William S.D. , Arnulf Adrien F. , Tolstoy Maya , Waldhauser Felix
Published: November 2019

Axial Seamount is a prominent volcano located at the intersection of the Juan de Fuca Ridge and the Cobb‐Eickelberg hot spot in the northeast Pacific Ocean that has erupted in 1998, 2011, and 2015. The 2015 eruption was recorded by a seven‐station seismic network in the southern part of the summit caldera that forms part of the Ocean Observatories Initiative Cabled Array. We utilize a data set of ~3,900 well‐recorded earthquakes from January 2015 to February 2017 and a three‐dimensional P wave velocity model obtained previously from active source data to conduct a joint inversion for three‐dimensional P and S wave velocities and hypocentral parameters. The resulting velocity models are used to relocate >76,000 earthquakes with ≥10 arrival times. The velocity models reveal a low‐velocity anomaly in the center of the southern caldera at depths less than ~2 km, which corresponds to the top of the magma chamber and is interpreted as a region that is intensely fractured by the cyclical deformation of the caldera. High velocities around the caldera rim are likely due to consolidated undeformed lava flows. Low VP/VS in the southern caldera is consistent with the presence of hydrothermal vapor. Low S wave velocities and high VP/VS in the northern caldera may indicate a region dominated by thin cracks caused by dike injection. The relocated earthquakes delineate outward‐dipping ring faults more clearly than previous studies and image a subvertical inward‐dipping fault within the network that connects to the east caldera wall and eruptive fissures.
Deep Seated Density Anomalies Across the Iberia‐Africa Plate Boundary and Its Topographic Response
Authors: Jiménez‐Munt I. , Torne M. , Fernàndez M. , Vergés J. , Kumar A. , Carballo A. , García‐Castellanos D.
Published: November 2019

The modes in which the lithosphere deforms during continental collision and the mechanisms involved are not well understood. While continental subduction and mantle delamination are often invoked in tectonophysical studies, these processes are difficult to be confirmed in more complex tectonic regions such as the Gibraltar Arc. We study the present‐day density and compositional structure of the lithosphere along a transect running from South Iberia to North Africa crossing the western Gibraltar Arc. This region is located in the westernmost continental segment of the African‐Eurasian plates, characterized by a diffuse transpressive plate boundary. An integrated and self‐consistent geophysical‐petrological methodology is used to model the lithosphere structure variations and the thermophysical properties of the upper mantle. The crustal structure is mainly constrained by seismic experiments and geological data, whereas the composition of the lithospheric mantle is constrained by xenolith data. The results show large lateral variations in the topography of the lithosphere‐asthenosphere boundary. We distinguish different chemical lithospheric mantle domains that reproduce the main trends of the geophysical observables and the modeled P and S wave seismic velocities. A sublithospheric body colder than the surrounding mantle is needed beneath the Betics‐Rif to adjust the measured potential fields. We link this body to the Iberian slab localized just to the east of the profile and having some effect on the geoid and Bouguer anomalies. Local isostasy allows explaining most of the topography, but an elastic thickness higher than 10 km is needed to explain local misfits between the Atlas and the Rif Mountains.
Spatiotemporal Evolution of Long‐ and Short‐Term Slow Slip Events in the Tokai Region, Central Japan, Estimated From a Very Dense GNSS Network During 2013–2016
Authors: Sakaue Hiromu , Nishimura Takuya , Fukuda Jun'ichi , Kato Teruyuki
Published: November 2019

We analyzed Global Navigation Satellite System (GNSS) data from 1 January 2008 to 31 January 2016 for the Tokai region of the Nankai subduction zone, in order to study long‐ and short‐term slow slip events (SSEs) on the subduction interface. The dataset included our new temporary stations to obtain high resolution observations with station spacing of about 5 km. Long‐ and short‐term SSEs have been reported in the Tokai region, over the past two decades. It is difficult to directly compare those SSEs because long‐term SSEs were observed by GNSS, while short‐term SSEs were mainly observed by tiltmeters and strainmeters. We applied a time‐dependent inversion with improved temporal resolution to GNSS data and successfully obtained the spatiotemporal evolution of long‐ and short‐term SSEs. Our results show the very slow and stable slip of a long‐term SSE with Mw 6.6, along with several episodes of accelerated slip associated with short‐term SSEs (Mw 6.0–6.1). Our results showed the details of the migrating slip patterns and slip rates for the short‐term SSEs and possible relation with low frequency tremor (LFT). LFT is more associated with smaller magnitude short‐term SSEs rather than the larger long‐term SSEs. However, the maximum daily slip rates for short‐term SSEs are an order of magnitude larger than those for the long‐term SSEs. This suggests an explanation that the LFT may be directly related to the loading of the plate interface by the short‐term SSEs.
Decadal Variation of the Kuroshio Intrusion Into the South China Sea During 1992–2016
Authors: Chen Yicheng , Zhai Fangguo , Li Peiliang
Published: November 2019

Decadal variation of the Kuroshio intrusion into the South China Sea (KIS) during 1992–2016 is investigated using high‐resolution Hybrid Coordinate Ocean Model reanalysis data. The results indicate that both the yearly occurrence frequency of the Kuroshio intrusion and Luzon Strait transport show significant decadal variations and were generally high in approximately 1993, 2003–2004, and 2015–2016 and low in 1998–1999 and 2009–2010. The KIS is closely connected to the decadal oscillation of the meridional sea surface height anomaly (SSHA) gradient west of the Luzon Strait (LS). Further analyses reveal that large‐scale wind forcing in the western tropical Pacific Ocean is a major factor regulating decadal variation of the KIS, while local wind forcing has little impact. Cyclonic wind stress curl anomalies (WSCAs) over the western tropical Pacific Ocean induce negative SSHAs that propagate westward to the eastern coast of the Philippines via upwelling Rossby waves, weakening the Kuroshio transport and consequently enhancing the KIS. In addition, signals of negative SSHAs can propagate clockwise along the Philippines as coastal Kelvin waves and hence strengthen the northward SSHA gradient west of the LS, eventually leading to a stronger KIS. The situation is reversed when anticyclonic WSCAs prevail in the western tropical Pacific Ocean. The Philippines‐Taiwan Oscillation is linked to decadal WSCAs over the western tropical Pacific Ocean and hence regulates the decadal KIS.
The Effect of Remote Sensing Resolution Limits on Aeolian Sandstone Measurements and the Reconstruction of Ancient Dune Fields on Mars: Numerical Experiment Using the Page Sandstone, Earth
Authors: Cardenas Benjamin T. , Swanson Travis , Goudge Timothy A. , Wagner R. Wayne , Mohrig David
Published: November 2019

The distribution of cross‐set thicknesses is important data for reconstructing ancient aeolian dune fields from the strata they accumulated, but most aeolian strata on Mars must be observed from satellite. We hypothesize that remote sensing resolution limits will affect cross‐set thickness measurements and the dune‐field reconstructions that follow. Here we test this hypothesis using a numerical experiment mimicking the effects of satellite image resolution limits performed on a distribution of aeolian cross‐set thicknesses measured in the field from the Jurassic Page Sandstone, Arizona, USA. Page set thicknesses are exponentially distributed, representing the accumulations of dry dune fields (no water table interactions with the dunes) in a state of net‐sediment bypass. When observed from satellite, set‐thickness measurements increase as adjacent sets become indistinguishable, based on the map‐view distance between their upper and lower bounding surfaces. This is termed the exposure distance of a cross set and is a function of (1) the set thickness, (2) the dip of the outcrop surface, and (3) the number of satellite image pixels required to detect a set (detection limit). By running experiments using outcrop dips from 1° to 60° and detection limits from 0.75 to 2.50 m (3 to 10 High‐Resolution Imaging Science Experiment pixels), we find that gently sloping surfaces (< 13°) at all detection limits are associated with the least blending of adjacent sets, conserving the net‐bypass interpretation made from the true set thicknesses. Although these results are specific to the Page, they can be used as a guide for future Mars work.
Loading and Bioavailability of Colloidal Phosphorus in the Estuarine Gradient of the Deer Creek‐Susquehanna River Transect in the Chesapeake Bay
Authors: Li Qiang , Yuan Hezhong , Li Hui , Wang Dengjun , Jin Yan , Jaisi Deb P.
Published: November 2019

Phosphorus (P) overloading is a major cause of surface water eutrophication and bottom water hypoxia. The incomplete understanding of different P pools and their corresponding bioavailability in the continuum from sources and sinks has limited the development of appropriate nutrient management strategies. Here we apply multistable isotope proxies to track colloids and identify whether specific P pools in colloids are biologically cycled at the Deer Creek‐Susquehanna River mouth stretch. Results showed that NaOH‐Pi is the most dominant P pool in the summer and winter seasons. Oxygen isotope values (δ18OP) of NaOH‐Pi and HNO3‐Pi pools of different size fractions of colloids are much heavier than the ranges of equilibrium values in the ambient water, which suggest that these two pools are recalcitrant against biological uptake. It further means isotopic signatures of these P pools could be used to identify the sources of colloids. Carbon (C) and nitrogen (N) isotope compositions of colloids showed that the contribution of terrestrial sources gradually decreases downstream of the river toward the bay and Deer Creek contributes disproportionately high amounts of colloids to the Susquehanna River. These findings provide valuable information on the loading of colloids and relative bioavailability of colloidal P pools in estuarine ecosystems.
Nature-inspired rollable electronics
Authors: Lee Gunhee , Choi Yong Whan , Lee Taemin , Lim Kyung Seob , Shin Jooyeon , Kim Taewi , Kim Hyun Kuk , Koo Bon-Kwon , Kim Han Byul , Lee Jong-Gu , Ahn Kihyeon , Lee Eunhan , Lee Min Suk , Jeon Jin , Yang Hee Seok , Won Phillip , Mo Seongho , Kim Namkeun , Jeong Myung Ho , Roh Yeonwook , Han Seungyong , Koh Je-Sung , Kim Sang Moon , Kang Daeshik , Choi Mansoo
Published: November 2019

Inspired by the rolling mechanism of the proboscis of a butterfly, rollable electronics that can be rolled and unrolled to a great extent on demand are developed. Generally, electronic devices that are attached to various surfaces to acquire biosignals require mechanical flexibility and sufficient adhesive force. The rollable platform provides sufficient force that grips onto the entire target surface without destroying the target organ. To prove the versatility of our device not only in gripping and detecting biosignals from micro objects but also in performing a variety of functions, thin-film electronics including a heater, strain sensor and temperature sensor are constructed on the rollable platform, and it is confirmed that all the electronics operate normally in the rolled and unrolled states without breakdown. Then, micro bio-objects are gripped by using the rollable platform, and their tiny motions are successfully detected with the sensor on the platform. Furthermore, the detection of the pulse wave signals of swine under diverse experimental conditions is successfully conducted by rolling up the rollable system around the blood vessel of the swine, the result of which proves the feasibility of a rollable platform as a biomedical device.
Mechanism of synergistic actin filament pointed end depolymerization by cyclase-associated protein and cofilin
Authors: Kotila Tommi , Wioland Hugo , Enkavi Giray , Kogan Konstantin , Vattulainen Ilpo , Jégou Antoine , Romet-Lemonne Guillaume , Lappalainen Pekka
Published: November 2019

The ability of cells to generate forces through actin filament turnover was an early adaptation in evolution. While much is known about how actin filaments grow, mechanisms of their disassembly are incompletely understood. The best-characterized actin disassembly factors are the cofilin family proteins, which increase cytoskeletal dynamics by severing actin filaments. However, the mechanism by which severed actin filaments are recycled back to monomeric form has remained enigmatic. We report that cyclase-associated-protein (CAP) works in synergy with cofilin to accelerate actin filament depolymerization by nearly 100-fold. Structural work uncovers the molecular mechanism by which CAP interacts with actin filament pointed end to destabilize the interface between terminal actin subunits, and subsequently recycles the newly-depolymerized actin monomer for the next round of filament assembly. These findings establish CAP as a molecular machine promoting rapid actin filament depolymerization and monomer recycling, and explain why CAP is critical for actin-dependent processes in all eukaryotes.
Continuous-variable tomography of solitary electrons
Authors: Fletcher J. D. , Johnson N. , Locane E. , See P. , Griffiths J. P. , Farrer I. , Ritchie D. A. , Brouwer P. W. , Kashcheyevs V. , Kataoka M.
Published: November 2019

A method for characterising the wave-function of freely-propagating particles would provide a useful tool for developing quantum-information technologies with single electronic excitations. Previous continuous-variable quantum tomography techniques developed to analyse electronic excitations in the energy-time domain have been limited to energies close to the Fermi level. We show that a wide-band tomography of single-particle distributions is possible using energy-time filtering and that the Wigner representation of the mixed-state density matrix can be reconstructed for solitary electrons emitted by an on-demand single-electron source. These are highly localised distributions, isolated from the Fermi sea. While we cannot resolve the pure state Wigner function of our excitations due to classical fluctuations, we can partially resolve the chirp and squeezing of the Wigner function imposed by emission conditions and quantify the quantumness of the source. This tomography scheme, when implemented with sufficient experimental resolution, will enable quantum-limited measurements, providing information on electron coherence and entanglement at the individual particle level.
Poly(A) inclusive RNA isoform sequencing (PAIso−seq) reveals wide-spread non-adenosine residues within RNA poly(A) tails
Authors: Liu Yusheng , Nie Hu , Liu Hongxiang , Lu Falong
Published: November 2019

Message RNA poly(A) tails are vital for their function and regulation. However, the full-length sequence of mRNA isoforms with their poly(A) tails remains undetermined. Here, we develop a method at single-cell level sensitivity that enables quantification of poly(A) tails along with the full-length cDNA while reading non-adenosine residues within poly(A) tails precisely, which we name poly(A) inclusive RNA isoform sequencing (PAIso−seq). Using this method, we can quantify isoform specific poly(A) tail length. More interestingly, we find that 17% of the mRNAs harbor non-A residues within the body of poly(A) tails in mouse GV oocytes. We show that PAIso−seq is sensitive enough to analyze single GV oocytes. These findings will not only provide an accurate and sensitive tool in studying poly(A) tails, but also open a door for the function and regulation of non-adenosine modifications within the body of poly(A) tails.
Optogenetic gamma stimulation rescues memory impairments in an Alzheimer’s disease mouse model
Authors: Etter Guillaume , van der Veldt Suzanne , Manseau Frédéric , Zarrinkoub Iman , Trillaud-Doppia Emilie , Williams Sylvain
Published: November 2019

Slow gamma oscillations (30–60 Hz) correlate with retrieval of spatial memory. Altered slow gamma oscillations have been observed in Alzheimer’s disease. Here, we use the J20-APP AD mouse model that displays spatial memory loss as well as reduced slow gamma amplitude and phase-amplitude coupling to theta oscillations phase. To restore gamma oscillations in the hippocampus, we used optogenetics to activate medial septal parvalbumin neurons at different frequencies. We show that optogenetic stimulation of parvalbumin neurons at 40 Hz (but not 80 Hz) restores hippocampal slow gamma oscillations amplitude, and phase-amplitude coupling of the J20 AD mouse model. Restoration of slow gamma oscillations during retrieval rescued spatial memory in mice despite significant plaque deposition. These results support the role of slow gamma oscillations in memory and suggest that optogenetic stimulation of medial septal parvalbumin neurons at 40 Hz could provide a novel strategy for treating memory deficits in AD.
MglA functions as a three-state GTPase to control movement reversals of Myxococcus xanthus
Authors: Galicia Christian , Lhospice Sébastien , Varela Paloma Fernández , Trapani Stefano , Zhang Wenhua , Navaza Jorge , Herrou Julien , Mignot Tâm , Cherfils Jacqueline
Published: November 2019

In Myxococcus xanthus, directed movement is controlled by pole-to-pole oscillations of the small GTPase MglA and its GAP MglB. Direction reversals require that MglA is inactivated by MglB, yet paradoxically MglA and MglB are located at opposite poles at reversal initiation. Here we report the complete MglA/MglB structural cycle combined to GAP kinetics and in vivo motility assays, which uncovers that MglA is a three-state GTPase and suggests a molecular mechanism for concerted MglA/MglB relocalizations. We show that MglA has an atypical GTP-bound state (MglA-GTP*) that is refractory to MglB and is re-sensitized by a feedback mechanism operated by MglA-GDP. By identifying and mutating the pole-binding region of MglB, we then provide evidence that the MglA-GTP* state exists in vivo. These data support a model in which MglA-GDP acts as a soluble messenger to convert polar MglA-GTP* into a diffusible MglA-GTP species that re-localizes to the opposite pole during reversals.
Climate-human interaction associated with southeast Australian megafauna extinction patterns
Authors: Saltré Frédérik , Chadoeuf Joël , Peters Katharina J. , McDowell Matthew C. , Friedrich Tobias , Timmermann Axel , Ulm Sean , Bradshaw Corey J. A.
Published: November 2019

The mechanisms leading to megafauna (>44 kg) extinctions in Late Pleistocene (126,000—12,000 years ago) Australia are highly contested because standard chronological analyses rely on scarce data of varying quality and ignore spatial complexity. Relevant archaeological and palaeontological records are most often also biased by differential preservation resulting in under-representated older events. Chronological analyses have attributed megafaunal extinctions to climate change, humans, or a combination of the two, but rarely consider spatial variation in extinction patterns, initial human appearance trajectories, and palaeoclimate change together. Here we develop a statistical approach to infer spatio-temporal trajectories of megafauna extirpations (local extinctions) and initial human appearance in south-eastern Australia. We identify a combined climate-human effect on regional extirpation patterns suggesting that small, mobile Aboriginal populations potentially needed access to drinkable water to survive arid ecosystems, but were simultaneously constrained by climate-dependent net landscape primary productivity. Thus, the co-drivers of megafauna extirpations were themselves constrained by the spatial distribution of climate-dependent water sources.
Non-canonical signalling mediates changes in fungal cell wall PAMPs that drive immune evasion
Authors: Pradhan Arnab , Avelar Gabriela M. , Bain Judith M. , Childers Delma , Pelletier Chloe , Larcombe Daniel E. , Shekhova Elena , Netea Mihai G. , Brown Gordon D. , Erwig Lars , Gow Neil A. R. , Brown Alistair J. P.
Published: November 2019

To colonise their host, pathogens must counter local environmental and immunological challenges. Here, we reveal that the fungal pathogen Candida albicans exploits diverse host-associated signals to promote immune evasion by masking of a major pathogen-associated molecular pattern (PAMP), β-glucan. Certain nutrients, stresses and antifungal drugs trigger β-glucan masking, whereas other inputs, such as nitrogen sources and quorum sensing molecules, exert limited effects on this PAMP. In particular, iron limitation triggers substantial changes in the cell wall that reduce β-glucan exposure. This correlates with reduced phagocytosis by macrophages and attenuated cytokine responses by peripheral blood mononuclear cells. Iron limitation-induced β-glucan masking depends on parallel signalling via the iron transceptor Ftr1 and the iron-responsive transcription factor Sef1, and the protein kinase A pathway. Our data reveal that C. albicans exploits a diverse range of specific host signals to trigger protective anticipatory responses against impending phagocytic attack and promote host colonisation.
ZFP161 regulates replication fork stability and maintenance of genomic stability by recruiting the ATR/ATRIP complex
Authors: Kim Wootae , Zhao Fei , Wu Rentian , Qin Sisi , Nowsheen Somaira , Huang Jinzhou , Zhou Qin , Chen Yuping , Deng Min , Guo Guijie , Luo Kuntian , Lou Zhenkun , Yuan Jian
Published: November 2019

DNA replication stress-mediated activation of the ATR kinase pathway is important for maintaining genomic stability. In this study, we identified a zinc finger protein, ZFP161 that functions as a replication stress response factor in ATR activation. Mechanistically, ZFP161 acts as a scaffolding protein to facilitate the interaction between RPA and ATR/ATRIP. ZFP161 binds to RPA and ATR/ATRIP through distinct regions and stabilizes the RPA–ATR–ATRIP complex at stalled replication forks. This function of ZFP161 is important to the ATR signaling cascade and genome stability maintenance. In addition, ZFP161 knockout mice showed a defect in ATR activation and genomic instability. Furthermore, low expression of ZFP161 is associated with higher cancer risk and chromosomal instability. Overall, these findings suggest that ZFP161 coordinates ATR/Chk1 pathway activation and helps maintain genomic stability.
Brain-to-cervical lymph node signaling after stroke
Authors: Esposito Elga , Ahn Bum Ju , Shi Jingfei , Nakamura Yoshihiko , Park Ji Hyun , Mandeville Emiri T. , Yu Zhanyang , Chan Su Jing , Desai Rakhi , Hayakawa Ayumi , Ji Xunming , Lo Eng H. , Hayakawa Kazuhide
Published: November 2019

After stroke, peripheral immune cells are activated and these systemic responses may amplify brain damage, but how the injured brain sends out signals to trigger systemic inflammation remains unclear. Here we show that a brain-to-cervical lymph node (CLN) pathway is involved. In rats subjected to focal cerebral ischemia, lymphatic endothelial cells proliferate and macrophages are rapidly activated in CLNs within 24 h, in part via VEGF-C/VEGFR3 signalling. Microarray analyses of isolated lymphatic endothelium from CLNs of ischemic mice confirm the activation of transmembrane tyrosine kinase pathways. Blockade of VEGFR3 reduces lymphatic endothelial activation, decreases pro-inflammatory macrophages, and reduces brain infarction. In vitro, VEGF-C/VEGFR3 signalling in lymphatic endothelial cells enhances inflammatory responses in co-cultured macrophages. Lastly, surgical removal of CLNs in mice significantly reduces infarction after focal cerebral ischemia. These findings suggest that modulating the brain-to-CLN pathway may offer therapeutic opportunities to ameliorate systemic inflammation and brain injury after stroke.
Sonic Hedgehog is expressed by hilar mossy cells and regulates cellular survival and neurogenesis in the adult hippocampus
Authors: Gonzalez-Reyes Luis E. , Chiang Chia-Chu , Zhang Mingming , Johnson Joshua , Arrillaga-Tamez Manuel , Couturier Nicholas H. , Reddy Neha , Starikov Lev , Capadona Jeffrey R. , Kottmann Andreas H. , Durand Dominique M.
Published: November 2019

Sonic hedgehog (Shh) is a multifunctional signaling protein governing pattern formation, proliferation and cell survival during embryogenesis. In the adult brain, Shh has neurotrophic function and is implicated in hippocampal neurogenesis but the cellular source of Shh in the hippocampus remains ill defined. Here, we utilize a gene expression tracer allele of Shh (Shh-nlacZ) which allowed the identification of a subpopulation of hilar neurons known as mossy cells (MCs) as a prominent and dynamic source of Shh within the dentate gyrus. AAV-Cre mediated ablation of Shh in the adult dentate gyrus led to a marked degeneration of MCs. Conversely, chemical stimulation of hippocampal neurons using the epileptogenic agent kainic acid (KA) increased the number of Shh+ MCs indicating that the expression of Shh by MCs confers a survival advantage during the response to excitotoxic insults. In addition, ablation of Shh in the adult dentate gyrus led to increased neural precursor cell proliferation and their migration into the subgranular cell layer demonstrating that MCs-generated Shh is a key modulator of hippocampal neurogenesis.
New Alzheimer’s disease model mouse specialized for analyzing the function and toxicity of intraneuronal Amyloid β oligomers
Authors: Ochiishi Tomoyo , Kaku Masami , Kiyosue Kazuyuki , Doi Motomichi , Urabe Takao , Hattori Nobutaka , Shimura Hideki , Ebihara Tatsuhiko
Published: November 2019

Oligomers of intracellular amyloid β protein (Aβ) are strongly cytotoxic and play crucial roles in synaptic transmission and cognitive function in Alzheimer’s disease (AD). However, there is currently no AD model mouse in which to specifically analyze the function of Aβ oligomers only. We have now developed a novel AD model mouse, an Aβ-GFP transgenic mouse (Aβ-GFP Tg), that expresses the GFP-fused human Aβ1-42 protein, which forms only Aβ oligomers within neurons throughout their life. The fusion proteins are expressed mainly in the hippocampal CA1-CA2 region and cerebral cortex, and are not secreted extracellularly. The Aβ-GFP Tg mice exhibit increased tau phosphorylation, altered spine morphology, decreased expressions of the GluN2B receptor and neuroligin in synaptic regions, attenuated hippocampal long-term potentiation, and impaired object recognition memory compared with non-Tg littermates. Interestingly, these dysfunctions have already appeared in 2–3-months-old animals. The Aβ-GFP fusion protein is bioactive and highly toxic, and induces the similar synaptic dysfunctions as the naturally generated Aβ oligomer derived from postmortem AD patient brains and synthetic Aβ oligomers. Thus, Aβ-GFP Tg mouse is a new tool specialized to analyze the function of Aβ oligomers in vivo and to find subtle changes in synapses in early symptoms of AD.
Sorsby Fundus Dystrophy Mutation in Tissue Inhibitor of Metalloproteinase 3 (TIMP3) promotes Choroidal Neovascularization via a Fibroblast Growth Factor-dependent Mechanism
Authors: Qi Jian Hua , Bell Brent , Singh Rupesh , Batoki Julia , Wolk Alyson , Cutler Alecia , Prayson Nicholas , Ali Mariya , Stoehr Heidi , Anand-Apte Bela
Published: November 2019

Choroidal neovascularization (CNV) leads to loss of vision in patients with Sorsby Fundus Dystrophy (SFD), an inherited, macular degenerative disorder, caused by mutations in the Tissue Inhibitor of Metalloproteinase-3 (TIMP3) gene. SFD closely resembles age-related macular degeneration (AMD), which is the leading cause of blindness in the elderly population of the Western hemisphere. Variants in TIMP3 gene have recently been identified in patients with AMD. A majority of patients with AMD also lose vision as a consequence of choroidal neovascularization (CNV). Thus, understanding the molecular mechanisms that contribute to CNV as a consequence of TIMP-3 mutations will provide insight into the pathophysiology in SFD and likely the neovascular component of the more commonly seen AMD. While the role of VEGF in CNV has been studied extensively, it is becoming increasingly clear that other factors likely play a significant role. The objective of this study was to test the hypothesis that basic Fibroblast Growth Factor (bFGF) regulates SFD-related CNV. In this study we demonstrate that mice expressing mutant TIMP3 (Timp3S179C/S179C) showed reduced MMP inhibitory activity with an increase in MMP2 activity and bFGF levels, as well as accentuated CNV leakage when subjected to laser injury. S179C mutant-TIMP3 in retinal pigment epithelial (RPE) cells showed increased secretion of bFGF and conditioned medium from these cells induced increased angiogenesis in endothelial cells. These studies suggest that S179C-TIMP3 may promote angiogenesis and CNV via a FGFR-1-dependent pathway by increasing bFGF release and activity.
A mass spectrometry guided approach for the identification of novel vaccine candidates in gram-negative pathogens
Authors: Hornburg Daniel , Kruse Tobias , Anderl Florian , Daschkin Christina , Semper Raphaela P. , Klar Kathrin , Guenther Anna , Mejías-Luque Raquel , Schneiderhan-Marra Nicole , Mann Matthias , Meissner Felix , Gerhard Markus
Published: November 2019

Vaccination is the most effective method to prevent infectious diseases. However, approaches to identify novel vaccine candidates are commonly laborious and protracted. While surface proteins are suitable vaccine candidates and can elicit antibacterial antibody responses, systematic approaches to define surfomes from gram-negatives have rarely been successful. Here we developed a combined discovery-driven mass spectrometry and computational strategy to identify bacterial vaccine candidates and validate their immunogenicity using a highly prevalent gram-negative pathogen, Helicobacter pylori, as a model organism. We efficiently isolated surface antigens by enzymatic cleavage, with a design of experiment based strategy to experimentally dissect cell surface-exposed from cytosolic proteins. From a total of 1,153 quantified bacterial proteins, we thereby identified 72 surface exposed antigens and further prioritized candidates by computational homology inference within and across species. We next tested candidate-specific immune responses. All candidates were recognized in sera from infected patients, and readily induced antibody responses after vaccination of mice. The candidate jhp_0775 induced specific B and T cell responses and significantly reduced colonization levels in mouse therapeutic vaccination studies. In infected humans, we further show that jhp_0775 is immunogenic and activates IFNγ secretion from peripheral CD4+ and CD8+ T cells. Our strategy provides a generic preclinical screening, selection and validation process for novel vaccine candidates against gram-negative bacteria, which could be employed to other gram-negative pathogens.
Higher body mass index is linked to altered hypothalamic microstructure
Authors: Thomas K. , Beyer F. , Lewe G. , Zhang R. , Schindler S. , Schönknecht P. , Stumvoll M. , Villringer A. , Witte A. V.
Published: November 2019

Animal studies suggest that obesity-related diets induce structural changes in the hypothalamus, a key brain area involved in energy homeostasis. Whether this translates to humans is however largely unknown. Using a novel multimodal approach with manual segmentation, we here show that a higher body mass index (BMI) selectively predicted higher proton diffusivity within the hypothalamus, indicative of compromised microstructure in the underlying tissue, in a well-characterized population-based cohort (n1 = 338, 48% females, age 21–78 years, BMI 18–43 kg/m²). Results were independent from confounders and confirmed in another independent sample (n2 = 236). In addition, while hypothalamic volume was not associated with obesity, we identified a sexual dimorphism and larger hypothalamic volumes in the left compared to the right hemisphere. Using two large samples of the general population, we showed that a higher BMI specifically relates to altered microstructure in the hypothalamus, independent from confounders such as age, sex and obesity-associated co-morbidities. This points to persisting microstructural changes in a key regulatory area of energy homeostasis occurring with excessive weight. Our findings may help to better understand the pathomechanisms of obesity and other eating-related disorders.
Single Source Thermal Evaporation of Two-dimensional Perovskite Thin Films for Photovoltaic Applications
Authors: Zheng Zhuang-Hao , Lan Hua-Bin , Su Zheng-Hua , Peng Huan-Xin , Luo Jing-Ting , Liang Guang-Xing , Fan Ping
Published: November 2019

Hybrid two-dimensional (2D) halide perovskites has been widely studied due to its potential application for high performance perovskite solar cells. Understanding the relationship between microstructural and opto-electronic properties is very important for fabricating high-performance 2D perovskite solar cell. In this work, the effect of solvent annealing on grain growth was investigated to enhance the efficiency of photovoltaic devices with 2D perovskite films based on (BA)2(MA)3Pb4I13 prepared by single-source thermal evaporation. Results show that solvent annealing with the introduction of solvent vapor can effectively enhance the crystallization of the (BA)2(MA)3Pb4I13 thin films and produce denser, larger-crystal grains. The thin films also display a favorable band gap of 1.896 eV, which benefits for increasing the charge-diffusion lengths. The solvent-annealed (BA)2(MA)3Pb4I13 thin-film solar cell prepared by single-source thermal evaporation shows an efficiency range of 2.54–4.67%. Thus, the proposed method can be used to prepare efficient large-area 2D perovskite solar cells.
A contralateral wing stabilizes a hovering hawkmoth under a lateral gust
Authors: Han Jong-Seob , Han Jae-Hung
Published: November 2019

Previous analysis on the lateral stability of hovering insects, which reported a destabilizing roll moment due to a lateral gust, has relied on the results of a single wing without considering a presence of the contralateral wing (wing-wing interaction). Here, we investigated the presence of the contralateral wing on the aerodynamic and flight dynamic characteristics of a hovering hawkmoth under a lateral gust. By employing a dynamically scaled-up mechanical model and a servo-driven towing system installed in a water tank, we found that the presence of the contralateral wing plays a significant role in the lateral static stability. The contralateral wing mitigated an excessive aerodynamic force on the wing at the leeward side, thereby providing a negative roll moment to the body. Digital particle image velocimetry revealed an attenuated vortical system of the leading-edge vortex. An excessive effective angle of attack in the single wing case, which was caused by the root vortex of previous half stroke, was reduced by a downwash of the contralateral wing. The contralateral wing also relocated a neutral point in close proximity to the wing hinge points above the actual center of gravity, providing a practical static margin to a hovering hawkmoth.
Towards a quantitative determination of strain in Bragg Coherent X-ray Diffraction Imaging: artefacts and sign convention in reconstructions
Authors: Carnis Jérôme , Gao Lu , Labat Stéphane , Kim Young Yong , Hofmann Jan P. , Leake Steven J. , Schülli Tobias U. , Hensen Emiel J. M. , Thomas Olivier , Richard Marie-Ingrid
Published: November 2019

Bragg coherent X-ray diffraction imaging (BCDI) has emerged as a powerful technique to image the local displacement field and strain in nanocrystals, in three dimensions with nanometric spatial resolution. However, BCDI relies on both dataset collection and phase retrieval algorithms that can induce artefacts in the reconstruction. Phase retrieval algorithms are based on the fast Fourier transform (FFT). We demonstrate how to calculate the displacement field inside a nanocrystal from its reconstructed phase depending on the mathematical convention used for the FFT. We use numerical simulations to quantify the influence of experimentally unavoidable detector deficiencies such as blind areas or limited dynamic range as well as post-processing filtering on the reconstruction. We also propose a criterion for the isosurface determination of the object, based on the histogram of the reconstructed modulus. Finally, we study the capability of the phasing algorithm to quantitatively retrieve the surface strain (i.e., the strain of the surface voxels). This work emphasizes many aspects that have been neglected so far in BCDI, which need to be understood for a quantitative analysis of displacement and strain based on this technique. It concludes with the optimization of experimental parameters to improve throughput and to establish BCDI as a reliable 3D nano-imaging technique.