bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms that may lead to high genetic divergence and to the invasive success of tall fleabane (Conyza sumatrensis; Asteraceae)
Authors: Ruiz Maycon Rodrigo , Mangolin Claudete Aparecida , de Oliveira Rubem Silvério , Mendes Rafael Romero , Takano Hudson Kagueyama , Eisele Tauana Gibim , Machado Maria de Fátima P. S.
Published: August 2021

Tall fleabane [Conyza sumatrensis (Retz.) E. Walker] is commonly invasive in agricultural fields, reducing yield in various infested crops. The current study investigates the genetic diversity within and between a significant number of invasive C. sumatrensis biotypes in soybean fields in southern, southeastern, and midwestern Brazil, using microsatellites as molecular markers. High and low observed and expected heterozygosity estimated in microsatellite loci supported our hypothesis that different levels of genetic diversity may be detected within biotypes from different invaded fields. Analysis of a significant number of biotypes in several fields showed high and low genetic diversity not associated with geographic distribution, bottleneck effect, or susceptibility to glyphosate. A deficit of heterozygous plants, high genetic divergence, and moderate allelic transference were also observed. Allelic fixation was different in the different biotypes. The bottleneck effect was seen in biotypes with reduced genetic diversity and in biotypes with the highest genetic diversity. Data on genetic diversity, bottleneck effect, and glyphosate resistance showed contrasts in biotypes from nearby invaded fields. Our study showed different genetic diversity levels in biotypes from invaded areas under the same climatic conditions.
Multiple Sklerose
Authors: Hansen Sascha , Wettinger Lena , Keune Philipp
Published: August 2021

Die Multiple Sklerose (MS) gilt als die häufigste chronisch-entzündliche ZNS-Erkrankung des jungen Erwachsenenalters. Der Krankheitsverlauf kann sehr variabel sein und die Behandlung erfordert oft auch ein fundiertes neuropsychologisches Fachwissen. In diesem Band werden zunächst grundlegende Kenntnisse über das Störungsbild, Ätiologie, Pathogenese und Störungstheorien dargestellt. Anschließend werden elementare neuropsychologische Kenntnisse für die fundierte Erfassung kognitiver Beeinträchtigungen vermittelt. Dabei wird auch auf die bei MS häufig auftretenden Faktoren Fatigue und Depressivität als wichtige zusätzliche Aspekte eingegangen. Darauf aufbauend werden die Möglichkeiten neuropsychologischer Therapie bei MS diskutiert. Ein beispielhafter Aufbau einer achtsamkeitsbasierten Intervention wird vorgestellt. Schließlich wird anhand eines ausführlichen Fallbeispiels das komplexe Zusammenwirken neuropsychologischer, psychosozialer und affektiver Variablen beleuchtet.
Stereotypes and Dehumanization
Authors: Rodríguez-Pérez Armando , Brambilla Marco , Betancor Verónica , Delgado Naira , Rodríguez-Gómez Laura
Published: August 2021

Abstract. Across two studies, we tested the relationship between the stereotype dimensions of sociability, morality, and competence and the two dimensions of humanness (human nature and human uniqueness). Study 1 considered real groups and revealed that sociability had greater power than morality in predicting human nature. For some groups, sociability also trumped competence in predicting human nature. By contrast, the attribution of human uniqueness was predicted by competence and morality. In Study 2, participants read a scenario depicting an unfamiliar group in stereotypical terms. Results showed that competence and sociability were the strongest predictors of human uniqueness and human nature, respectively. Although with nuances, both studies revealed that sociability, morality, and competence relate differently to the two dimensions of humanness.
Impacts of Tropical Cyclones on the Caribbean Under Future Climate Conditions
Authors: Kleptsova Olga S. , Dijkstra Henk A. , van Westen René M. , van der Boog Carine G. , Katsman Caroline A. , James Rebecca K. , Bouma Tjeerd J. , Klees Roland , Riva Riccardo E. M. , Slobbe D. Cornelis , Zijlema Marcel , Pietrzak Julie D.
Published: August 2021

Joint effects of the dynamic sea‐level rise projected changes in the large‐scale atmosphere/ocean circulation, and wave climate on hurricane‐induced extreme water levels in the Caribbean region are assessed. We use the 2D‐depth integrated ADCIRC + SWAN wave‐ocean model, baroclinically coupled to an ocean‐eddying version of the Community Earth System Model, to compare impacts of the September 2017 hurricanes with projected impacts of similar hypothetical tropical storms occurring in the future. The model predicts only minor changes in the hurricane‐induced extreme water levels for those Caribbean islands which were severely devastated by the 2017 tropical storms (Irma and Maria). That is, provided that the hurricane intensity remains at the present‐day level, the global mean sea‐level rise is the main future coastal flood risk factor.
Undertaking Adventure to Make Sense of Subglacial Plumes
Authors: Podolskiy Evgeny
Published: August 2021

Novel observations and inventive analyses of glacial discharge in Greenland have revealed new insights into the irregular and chaotic nature of ice-ocean interactions at glacial calving fronts.
A New Unconstrained Approach to GNSS Atmospheric Water Vapor Tomography
Authors: Miranda P. M. A. , Mateus P.
Published: August 2021

A new atmospheric tomographic model totally based on Global Navigation Satellite System (GNSS) observations is proposed and tested against field observations. The method does not require a first guess, does not contain specific constraints on the variability of water vapor density inside the tomographic domain, and is able to produce reasonable results at 6 km horizontal and 500 m vertical resolutions, from short (30 min) GNSS data samples. The inversion method uses the Moore‐Penrose pseudoinverse, which is made possible by increasing the rank of the design matrix through angular interpolation and extrapolation of the observations. Comparisons against 30 consecutive 4‐h radiosonde observations and model simulations suggest the ability of the method to detect inversions and local maxima aloft, and behave sensibly in the far‐field. Further improvements from this method may be expected from higher density and multi‐constellation networks.
Low‐Temperature Magnetic Properties of Marine Sediments—Quantifying Magnetofossils, Superparamagnetism, and Maghemitization: Eastern Mediterranean Examples
Authors: Qian Yao , Heslop David , Roberts Andrew P. , Hu Pengxiang , Zhao Xiang , Liu Yan , Li Jinhua , Grant Katharine M. , Rohling Eelco J.
Published: August 2021

Periodic and marked redox changes in eastern Mediterranean marine sediments drive environmental and diagenetic changes to which magnetic minerals are sensitive. Magnetic property changes, therefore, provide useful indications of paleoceanographic conditions during and after periods of organic‐rich sediment (sapropel) deposition. Magnetic properties of eastern Mediterranean sediments at room temperature have been studied for decades; however, few studies have considered low‐temperature magnetic properties. Here, we investigate the low‐temperature (10–300 K) magnetic properties of different eastern Mediterranean sediment types combined with room temperature (∼300 K) magnetic properties, transmission electron microscopy, and calibrated X‐ray fluorescence elemental data to illustrate the valuable information that can be obtained from low‐temperature magnetic analysis of sediments. Our low‐temperature magnetic results suggest that magnetite magnetofossils and superparamagnetic (SP) particles occur widely in eastern Mediterranean sediments. SP particle contents are highest in diagenetically reduced intervals associated with sapropels. In contrast, magnetite magnetofossils are most abundant in oxidation fronts at the tops of sapropels, where strong redox gradients formed, but are also widespread throughout other sedimentary intervals that have not been subjected to extensive reductive diagenesis. Moreover, the surfaces of magnetite particles are maghemitized (i.e., partially oxidized) in oxidation fronts at the tops of sapropels, and in other oxic sediment intervals. Our results demonstrate the value of LT magnetic measurements for quantifying diverse sedimentary magnetic signals of interest in environmental magnetism when studying paleoceanographic and paleoenvironmental processes.
Error Assessment of GRACE and GRACE Follow‐On Mass Change
Authors: Chen Jianli , Tapley Byron , Tamisiea Mark E. , Save Himanshu , Wilson Clark , Bettadpur Srinivas , Seo Ki‐Weon
Published: August 2021

We carry out a comprehensive error assessment of Gravity Recovery and Climate Experiment (GRACE) and GRACE Follow‐On (GFO) Release‐6 (RL06) solutions from the Center for Space Research (CSR) at the University of Texas at Austin, NASA Jet Propulsion Laboratory (JPL), and Geoforschungszentrum (GFZ). The study covers the period April 2002 to August 2020 and uses two different methods, one based upon open ocean residuals (OOR) and the other a Three‐Cornered Hat (TCH) calculation. General results from the two methods are similar. With 300 km Gaussian smoothing OOR RMS errors for CSR, JPL, and GFZ solutions are ∼2.01, 3.19, and 3.67 cm, respectively. With additional decorrelation filtering OOR RMS values are reduced to ∼1.24, 1.53, and 1.69 cm, respectively. TCH analysis also shows that CSR has the lowest noise levels with similar RMS values, and additional decorrelation filtering reduces error levels. TCH may underestimate errors if there are common errors among geophysical background models. Errors in GFO's first two years (25 solutions for 2018.06 to 2020.08) are comparable to those of GRACE when zonal degree 2 and 3 coefficients are replaced by Satellite Laser Ranging estimates. The OOR method reveals mismodeled intra‐seasonal dynamic ocean signals associated with the Argentine Gyre during de‐aliasing, while the TCH method shows differences between ocean tide models near Australia and Antarctica. Both OOR and TCH RMS analysis offer a means to assess the noise level of GRACE/GFO estimated mass change. The actual uncertainty of GRACE/GFO estimate averaged (or totaled) over a given region is also affected by other error sources.
Mechanism of the Centennial Subpolar North Atlantic Cooling Trend in the FGOALS‐g2 Historical Simulation
Authors: Fan Yifei , Lu Jianhua , Li Laifang
Published: August 2021

A cold blob, manifested as a centennial cooling trend in sea surface temperature (SST), is observed in the mid‐latitude North Atlantic. The presence of the cold blob is hypothesized as an evidence of a slowdown of Atlantic Meridional Overturning Circulation (AMOC), based on paleoclimate proxies and global climate models (GCMs). However, the performance of GCMs in simulating the cold blob remains unsatisfactory in terms of the SST cooling rate and the spatial extent. This study investigates the forcing mechanism of the cold blob using the Flexible Global Ocean‐Atmosphere‐Land System Model Grid‐point version 2 (FGOALS‐g2), a GCM that reasonably simulates the observed cooling trend in the subpolar North Atlantic and its spatial pattern. Surface heat budget analysis suggests that the cold blob is largely a result of the imbalance between changes in the heat storage and surface turbulent heat fluxes, exhibiting a cooling and warming effect, respectively. Investigation of ocean heat content indicates that heat advection into the cold blob region has decreased, mainly due to ocean circulation changes. However, in the FGOALS‐g2, both the AMOC slowdown and the reduced meridional heat transport explain a limited portion (less than 50%) of the cold blob sea surface temperature anomaly trend. Overall, complementing existing studies that attribute the cold blob to an AMOC slowdown, our results suggest that additional processes, including subpolar gyre circulation and a synergy between the atmosphere and the ocean, are at work in the formation of the cold blob.
Observations of Nighttime Clouds Over Chiba, Japan, Using Digital Cameras and Satellite Images
Authors: Lagrosas N. , Shiina T. , Kuze H.
Published: August 2021

Nighttime cloud cover (CC) is analyzed from the data observed for 34 months over Chiba, Japan, using continuously operated digital cameras. The normal camera works in the visible region, providing quantitative and temporal changes of nighttime CC. The second camera captures sky images without the near‐infrared cut filter, and by applying the thresholding method, we obtain information on the temporal changes of thin (pixel values between 72 and 115) and thick (>115) clouds. Comparing the CC from the visible camera with cloud fraction from Atmospheric Infrared Sounder (AIRS) shows that long‐term data from the camera are valuable for correcting the underestimation of the cloud fraction product from AIRS for low‐level clouds. Furthermore, a comparison between the near‐ground temperature and CC results in estimating the seasonal changes of feedback effects of upward thermal radiation from the ground. The current results reveal that thick clouds contribute to longwave cloud forcing (LWCF) below 100 Wm−2, while thin clouds with CC below 30% contribute to LWCF below 10.2 Wm−2.
The Role of Eyewall Turbulent Transport in the Pathway to Intensification of Tropical Cyclones
Authors: Zhu Ping , Hazelton Andrew , Zhang Zhan , Marks Frank D. , Tallapragada Vijay
Published: August 2021

In a tropical cyclone (TC), turbulence not only exists in the planetary boundary layer (PBL) but also can be generated above the PBL by the cloud processes in the eyewall and rainbands. It is found that the Hurricane Analysis and Forecast System (HAFS), a new multi‐scale operational model for TC prediction, fails to capture the intense turbulent mixing in eyewall and rainband clouds due to a poor estimation of static stability in clouds. The problem is fixed by including the effects of multi‐phase water in the stability calculation. Simulations of 21 TCs and tropical storms in the North Atlantic basin of 2016–2019 hurricane seasons totaling 118 forecast cycles show that the stability correction substantially improves HAFS's skill in predicting storm track and intensity. Analyses of HAFS's simulations of Hurricane Michael (2018) show that the positive tendency of vortex's tangential wind resulting from the radially inward transport of absolute vorticity dominates the eddy correlation tendencies induced by the model‐resolved asymmetric eddies and serves as a main mechanism for the rapid intensification of Michael. The sub‐grid scale (SGS) turbulent transport above the PBL in the eyewall plays a pivotal role in initiating a positive feedback among the eyewall convection, mean secondary overturning circulation, vortex acceleration via the inward transport of absolute vorticity, surface evaporation, and radial convergence of moisture in the PBL. Without the SGS transport above the PBL, the model‐resolved vertical transport alone may not be sufficient in initiating the positive feedback underlying the rapid intensification of TCs.
Adapting the MPAS Dynamical Core for Applications Extending Into the Thermosphere
Authors: Klemp J. B. , Skamarock W. C.
Published: August 2021

To extend the nonhydrostatic global Model for Prediction Across Scales (MPAS) for deep‐atmosphere (geospace) applications, we have modified the model equations and numerics to include variable atmospheric composition and (potentially large) molecular viscosity and thermal conductivity. The split‐explicit numerical integration techniques in MPAS remain stable in idealized test cases for atmospheric domains extending into the upper thermosphere and continue to provide an efficient numerical framework for nonhydrostatic simulations. Variations in the atmospheric constituents influence the dynamical equations by altering the heat capacity and ideal gas constants. These feedbacks require little alteration of the dynamical equations although our testing reveals that the amplitude of disturbances may be sensitive to even small variations in the thermodynamic coefficients. Although the potential temperature is no longer formally conserved for adiabatic flow, it remains effective as a prognostic thermodynamic variable in the model equations. Molecular viscosity and thermal conductivity are dominant influences in the upper thermosphere and are represented implicitly in the model numerics. Because of the large magnitude of these terms, their treatment, though stable, may significantly under represent the true magnitude of their damping effects. Further consideration of these deep‐atmosphere extensions to MPAS will be explored in more realistic simulations of thermospheric dynamics.
A Comparison of Data‐Driven Approaches to Build Low‐Dimensional Ocean Models
Authors: Agarwal Niraj , Kondrashov D. , Dueben P. , Ryzhov E. , Berloff P.
Published: August 2021

We present a comprehensive inter‐comparison of linear regression (LR), stochastic, and deep‐learning approaches for reduced‐order statistical emulation of ocean circulation. The reference data set is provided by an idealized, eddy‐resolving, double‐gyre ocean circulation model. Our goal is to conduct a systematic and comprehensive assessment and comparison of skill, cost, and complexity of statistical models from the three methodological classes. The model based on LR is considered as a baseline. Additionally, we investigate its additive white noise augmentation and a multi‐level stochastic approach, deep‐learning methods, hybrid frameworks (LR plus deep‐learning), and simple stochastic extensions of deep‐learning and hybrid methods. The assessment metrics considered are: root mean squared error, anomaly cross‐correlation, climatology, variance, frequency map, forecast horizon, and computational cost. We found that the multi‐level linear stochastic approach performs the best for both short‐ and long‐timescale forecasts. The deep‐learning hybrid models augmented by additive state‐dependent white noise came second, while their deterministic counterparts failed to reproduce the characteristic frequencies in climate‐range forecasts. Pure deep learning implementations performed worse than LR and its simple white noise augmentation. Skills of LR and its white noise extension were similar on short timescales, but the latter performed better on long timescales, while LR‐only outputs decay to zero for long simulations. Overall, our analysis promotes multi‐level LR stochastic models with memory effects, and hybrid models with linear dynamical core augmented by additive stochastic terms learned via deep learning, as a more practical, accurate, and cost‐effective option for ocean emulation than pure deep‐learning solutions.
Weak Temperature Gradient Modeling of Convection in OTREC
Authors: Raymond D. J. , Fuchs‐Stone Ž.
Published: August 2021

Convection observed in the OTREC field program in the tropical east Pacific and southwest Caribbean is simulated using a cloud‐resolving model employing the weak temperature gradient approximation. Simulations are made using reference profiles derived from three‐dimensional variational analyses of dropsonde data selected for different ranges of saturation fraction, a kind of column relative humidity. For each of these humidity ranges, two simulations are performed, one with ventilation of the model domain by the ambient wind (a new model feature) and one without this ventilation. The model results using ventilation are much closer to observation than those without ventilation, especially for drier environments. These results have strong implications for the distribution of ITCZ convection in the east Pacific and for the construction of cumulus parameterizations.
Geomagnetic Storm Occurrence and Their Relation With Solar Cycle Phases
Authors: Reyes Paula I. , Pinto Victor A. , Moya Pablo S.
Published: August 2021

Using a time series of geomagnetic storm events between 1957 and 2019, obtained by selecting storms where −50 nT, we have analyzed the probability of occurrence of moderate, intense, and severe events. Considering that geomagnetic storms can be modeled as stochastic processes with a log‐normal probability distribution over their minimum index, the dataset was separated according to solar cycle (SC) and SC phases, and the distributions of events were fitted through maximum likelihood method in order to characterize the occurrence of storms in each cycle and phase, and then compare those occurrences to the SC24. Our results show that there is a strong dependence between the occurrence of intense storms, with  −100 nT, and the strength of the SC measured by the sunspot numbers. In particular, SC24 is very similar to SC20. However, when comparing the occurrence of storms by SC phases, events tend to show similar activity toward the minimum phase and have significant differences in the maximum phases. By looking at the value—the fit log‐normal distribution “width” parameter—characteristic of the occurrence rate of storms, we have found that the (the sigma value in the descending phase of one cycle) shows the highest correlation () with (the sigma value in the maximum phase of the next cycle) which allows us to estimate the occurrence rate of storms for SC25 to be similar to those of SC21 and SC22, suggesting a more intense cycle than the one that just ended.
High‐Resolution Seismic Profiling in the Hanging Wall of the Southern Fault Section Ruptured During the 2016 Mw 6.5 Central Italy Earthquake
Authors: Villani Fabio , Maraio Stefano , Bruno Pier Paolo , Improta Luigi , Wood Kieran , Pucci Stefano , Civico Riccardo , Sapia Vincenzo , De Martini Paolo Marco , Brunori Carlo Alberto , Doglioni Carlo , Pantosti Daniela
Published: August 2021

The Vettore–Bove normal fault system in central Italy ruptured during the 2016 MW 6.5 Norcia earthquake causing extensive surface faulting. At the Pian Grande di Castelluccio hanging wall basin, along the southern section of the fault ruptured during the MW 6.5 mainshock, we performed a high‐resolution seismic reflection/refraction experiment aimed at (a) imaging the shallow pattern of the fault system, and (b) reconstructing the architecture of the continental infill. We collected three profiles for a total length of ∼8 km. We used a reflection processing flow and non‐linear refraction tomography to obtain migrated stack sections and P‐wave velocity images resolved down to the depth of the pre‐Quaternary substratum. The main profile in the northern part of the basin crosses the westernmost splays of the ruptured fault zone striking N150°–170°. Seismic imaging unravels a ∼1 km‐wide fault zone comprising three W‐throwing splays and subsidiary faults, which affect the continental infill and produce a minimum aggregate Quaternary throw of ∼400 ± 100 m. Recent deformation is localized in this part of the surveyed fault section, attesting active displacement accumulation of the Vettore–Bove fault system. The other profiles in the central‐southern part of the basin show additional faults, likely striking N20°–40° and which concurred to generate a ∼500 m‐deep depocenter. These faults were mostly active during an early extensional phase; however, one of them likely displaces shallow layers with a throw close to the resolution limit of seismic data (<10 m), suggesting activity in the Late Pleistocene.
Estimating Terrestrial Snow Mass via Multi‐Sensor Assimilation of Synthetic AMSR‐E Brightness Temperature Spectral Differences and Synthetic GRACE Terrestrial Water Storage Retrievals
Authors: Wang Jing , Forman Barton A. , Girotto Manuela , Reichle Rolf H.
Published: August 2021

This study explores multi‐sensor data assimilation (DA) using synthetic Advanced Microwave Scanning Radiometer (AMSR‐E) passive microwave brightness temperature spectral differences () and synthetic Gravity Recovery and Climate Experiment (GRACE) terrestrial water storage (TWS) retrievals to improve estimates of snow water equivalent (SWE), subsurface water storage, and TWS across snow‐covered terrain. Results show that multi‐sensor DA improves SWE estimates by reducing the RMSE by 14.1% relative to a model‐only simulation. Multi‐sensor assimilation also yields the smallest TWS RMSE (reduced by 13.0% relative to a model‐only simulation). However, multi‐sensor DA does not always yield complementary updates, and can sometimes lead to conflicting changes to SWE, where the assimilation of synthetic generates positive SWE increments while the assimilation of synthetic TWS removes SWE, which can ultimately degrade the posterior SWE estimates. This synthetic experiment provides useful insight for future DA experiments using real‐world AMSR‐E/AMSR‐2 observations and GRACE/GRACE‐FO TWS retrievals to better characterize terrestrial freshwater storage across regional scales.
The prefrontal cortex and (uniquely) human cooperation: a comparative perspective
Authors: Zoh Yoonseo , Chang Steve W. C. , Crockett Molly J.
Published: August 2021

Humans have an exceptional ability to cooperate relative to many other species. We review the neural mechanisms supporting human cooperation, focusing on the prefrontal cortex. One key feature of human social life is the prevalence of cooperative norms that guide social behavior and prescribe punishment for noncompliance. Taking a comparative approach, we consider shared and unique aspects of cooperative behaviors in humans relative to nonhuman primates, as well as divergences in brain structure that might support uniquely human aspects of cooperation. We highlight a medial prefrontal network common to nonhuman primates and humans supporting a foundational process in cooperative decision-making: valuing outcomes for oneself and others. This medial prefrontal network interacts with lateral prefrontal areas that are thought to represent cooperative norms and modulate value representations to guide behavior appropriate to the local social context. Finally, we propose that more recently evolved anterior regions of prefrontal cortex play a role in arbitrating between cooperative norms across social contexts, and suggest how future research might fruitfully examine the neural basis of norm arbitration.
Maximum antigen diversification in a lyme bacterial population and evolutionary strategies to overcome pathogen diversity
Authors: Di Lia , Akther Saymon , Bezrucenkovas Edgaras , Ivanova Larisa , Sulkow Brian , Wu Bing , Mneimneh Saad , Gomes-Solecki Maria , Qiu Wei-Gang
Published: August 2021

Natural populations of pathogens and their hosts are engaged in an arms race in which the pathogens diversify to escape host immunity while the hosts evolve novel immunity. This co-evolutionary process poses a fundamental challenge to the development of broadly effective vaccines and diagnostics against a diversifying pathogen. Based on surveys of natural allele frequencies and experimental immunization of mice, we show high antigenic specificities of natural variants of the outer surface protein C (OspC), a dominant antigen of a Lyme Disease-causing bacterium (Borrelia burgdorferi). To overcome the challenge of OspC antigenic diversity to clinical development of preventive measures, we implemented a number of evolution-informed strategies to broaden OspC antigenic reactivity. In particular, the centroid algorithm—a genetic algorithm to generate sequences that minimize amino-acid differences with natural variants—generated synthetic OspC analogs with the greatest promise as diagnostic and vaccine candidates against diverse Lyme pathogen strains co-existing in the Northeast United States. Mechanistically, we propose a model of maximum antigen diversification (MAD) mediated by amino-acid variations distributed across the hypervariable regions on the OspC molecule. Under the MAD hypothesis, evolutionary centroids display broad cross-reactivity by occupying the central void in the antigenic space excavated by diversifying natural variants. In contrast to vaccine designs based on concatenated epitopes, the evolutionary algorithms generate analogs of natural antigens and are automated. The novel centroid algorithm and the evolutionary antigen designs based on consensus and ancestral sequences have broad implications for combating diversifying pathogens driven by pathogen–host co-evolution.
The enhancing effects of testosterone in exposure treatment for social anxiety disorder: a randomized proof-of-concept trial
Authors: Hutschemaekers Moniek H. M. , de Kleine Rianne A. , Hendriks Gert-Jan , Kampman Mirjam , Roelofs Karin
Published: August 2021

Individuals with a social anxiety disorder (SAD) show hypofunctioning of the hypothalamus–pituitary-gonadal (HPG) axis, which is linked to social fear and avoidance behavior. As testosterone administration has been shown to facilitate social-approach behavior in this population, it may enhance the effectiveness of exposure treatment. In this proof-of-concept study, we performed a randomized clinical assay in which 55 women diagnosed with SAD received two exposure therapy sessions. Session 1 was supplemented with either testosterone (0.50 mg) or placebo. Next, transfer effects of testosterone augmentation on within-session subjective fear responses and SAD symptom severity were assessed during a second, unenhanced exposure session (session 2) and at a 1-month follow-up, respectively. The participants having received testosterone showed a more reactive fear pattern, with higher peaks and steeper reductions in fear levels in session 2. Post-hoc exploration of moderating effects of endogenous testosterone levels, revealed that this pattern was specific for women with high basal testosterone, both in the augmented and in the transfer session. In contrast, the participants with low endogenous testosterone showed reduced peak fear levels throughout session 1, again with transfer to the unenhanced session. Testosterone did not significantly affect self-reported anxiety. The effects of testosterone supplementation on fear levels show transfer to non-enhanced exposure, with effects being modulated by endogenous testosterone. These first preliminary results indicate that testosterone may act on important fear mechanisms during exposure, providing the empirical groundwork for further exploration of multi-session testosterone-enhanced exposure treatment for SAD.
Traumatic events during childhood and its risks to substance use in adulthood: an observational and genome-wide by environment interaction study in UK Biobank
Authors: Cheng Shiqiang , Wen Yan , Liu Li , Cheng Bolun , Liang Chujun , Ye Jing , Chu Xiaomeng , Yao Yao , Jia Yumeng , Kafle Om Prakash , Zhang Feng
Published: August 2021

We aimed to explore the underlying genetic mechanisms of traumatic events during childhood affecting the risks of adult substance use in present study. Using UK Biobank cohort, linear regression model was first applied to assess the relationships between cigarette smoking and alcohol drinking in adults with traumatic events during childhood, including felt hated by family member (41,648–111,465), felt loved (46,394–124,481) and sexually molested (47,598–127,766). Using traumatic events as exposure variables, genome-wide by environment interaction study was then performed by PLINK 2.0 to identify cigarette smoking and alcohol drinking associated genes interacting with traumatic events during childhood. We found that the frequency of cigarette smoking was significantly associated with felt hated by family member (coefficient = 0.42, P < 1.0 × 10–9), felt loved (coefficient = −0.31, P < 1.0 × 10–9) and sexually molested (coefficient = 0.46, P < 1.0 × 10–9). We also observed weaker associations of alcohol drinking with felt hated by family member (coefficient = 0.08, P = 3.10 × 10–6) and felt loved (coefficient = −0.06, P = 3.15 × 10–7). GWEIS identified multiple candidate loci interacting with traumatic events, such as CTNNA3 (rs189142060, P = 4.23 × 10–8) between felt hated by family member and the frequency of cigarette smoking, GABRG3 (rs117020886, P = 2.77 × 10–8) between felt hated by family member and the frequency of alcohol drinking. Our results suggested the significant impact of traumatic events during childhood on the risk of cigarette smoking and alcohol drinking.
Defining the therapeutic selective dependencies for distinct subtypes of PI3K pathway-altered prostate cancers
Authors: Mao Ninghui , Zhang Zeda , Lee Young Sun , Choi Danielle , Rivera Aura Agudelo , Li Dan , Lee Cindy , Haywood Samuel , Chen Xiaoping , Chang Qing , Xu Guotai , Chen Hsuan-An , de Stanchina Elisa , Sawyers Charles , Rosen Neal , Hsieh Andrew C. , Chen Yu , Carver Brett S.
Published: August 2021

Previous studies have suggested that PTEN loss is associated with p110β signaling dependency, leading to the clinical development of p110β-selective inhibitors. Here we use a panel pre-clinical models to reveal that PI3K isoform dependency is not governed by loss of PTEN and is impacted by feedback inhibition and concurrent PIK3CA/PIK3CB alterations. Furthermore, while pan-PI3K inhibition in PTEN-deficient tumors is efficacious, upregulation of Insulin Like Growth Factor 1 Receptor (IGF1R) promotes resistance. Importantly, we show that this resistance can be overcome through targeting AKT and we find that AKT inhibitors are superior to pan-PI3K inhibition in the context of PTEN loss. However, in the presence of wild-type PTEN and PIK3CA-activating mutations, p110α-dependent signaling is dominant and selectively inhibiting p110α is therapeutically superior to AKT inhibition. These discoveries reveal a more nuanced understanding of PI3K isoform dependency and unveil novel strategies to selectively target PI3K signaling nodes in a context-specific manner.
High-throughput computational-experimental screening protocol for the discovery of bimetallic catalysts
Authors: Yeo Byung Chul , Nam Hyunji , Nam Hyobin , Kim Min-Cheol , Lee Hong Woo , Kim Sung-Chul , Won Sung Ok , Kim Donghun , Lee Kwan-Young , Lee Seung Yong , Han Sang Soo
Published: August 2021

To accelerate the discovery of materials through computations and experiments, a well-established protocol closely bridging these methods is required. We introduce a high-throughput screening protocol for the discovery of bimetallic catalysts that replace palladium (Pd), where the similarities in the electronic density of states patterns were employed as a screening descriptor. Using first-principles calculations, we screened 4350 bimetallic alloy structures and proposed eight candidates expected to have catalytic performance comparable to that of Pd. Our experiments demonstrate that four bimetallic catalysts indeed exhibit catalytic properties comparable to those of Pd. Moreover, we discover a bimetallic (Ni-Pt) catalyst that has not yet been reported for H2O2 direct synthesis. In particular, Ni61Pt39 outperforms the prototypical Pd catalyst for the chemical reaction and exhibits a 9.5-fold enhancement in cost-normalized productivity. This protocol provides an opportunity for the catalyst discovery for the replacement or reduction in the use of the platinum-group metals.
A systems biology model of junctional localization and downstream signaling of the Ang–Tie signaling pathway
Authors: Zhang Yu , Kontos Christopher D. , Annex Brian H. , Popel Aleksander S.
Published: August 2021

The Ang–Tie signaling pathway is an important vascular signaling pathway regulating vascular growth and stability. Dysregulation in the pathway is associated with vascular dysfunction and numerous diseases that involve abnormal vascular permeability and endothelial cell inflammation. The understanding of the molecular mechanisms of the Ang–Tie pathway has been limited due to the complex reaction network formed by the ligands, receptors, and molecular regulatory mechanisms. In this study, we developed a mechanistic computational model of the Ang–Tie signaling pathway validated against experimental data. The model captures and reproduces the experimentally observed junctional localization and downstream signaling of the Ang–Tie signaling axis, as well as the time-dependent role of receptor Tie1. The model predicts that Tie1 modulates Tie2’s response to the context-dependent agonist Ang2 by junctional interactions. Furthermore, modulation of Tie1’s junctional localization, inhibition of Tie2 extracellular domain cleavage, and inhibition of VE-PTP are identified as potential molecular strategies for potentiating Ang2’s agonistic activity and rescuing Tie2 signaling in inflammatory endothelial cells.
AZP2006, a new promising treatment for Alzheimer’s and related diseases
Authors: Callizot N. , Estrella C. , Burlet S. , Henriques A. , Brantis C. , Barrier M. , Campanari M. L. , Verwaerde P.
Published: August 2021

Progranulin (PGRN) is a protein with multiple functions including the regulation of neuroinflammation, neuronal survival, neurite and synapsis growth. Although the mechanisms of action of PGRN are currently unknown, its potential therapeutic application in treating neurodegenerative diseases is huge. Thus, strategies to increase PGRN levels in patients could provide an effective treatment. In the present study, we investigated the effects of AZP2006, a lysotropic molecule now in phase 2a clinical trial in Progressive Supranuclear Palsy patients, for its ability to increase PGRN level and promote neuroprotection. We showed for the first time the in vitro and in vivo neuroprotective effects of AZP2006 in neurons injured with Aβ1–42 and in two different pathological animal models of Alzheimer’s disease (AD) and aging. Thus, the chronic treatment with AZP2006 was shown to reduce the loss of central synapses and neurons but also to dramatically decrease the massive neuroinflammation associated with the animal pathology. A deeper investigation showed that the beneficial effects of AZP2006 were associated with PGRN production. Also, AZP2006 binds to PSAP (the cofactor of PGRN) and inhibits TLR9 receptors normally responsible for proinflammation when activated. Altogether, these results showed the high potential of AZP2006 as a new putative treatment for AD and related diseases.
Short-term cell death in tissues of Pulsatilla vernalis seeds from natural and ex situ conserved populations
Authors: Zielińska Katarzyna M. , Kaźmierczak Andrzej , Michalska Ewa
Published: August 2021

Pulsatilla vernalis is a IUCN listed species that occurs in mountain and lowland habitats. The seeds collected from different populations are remarkably diverse in their viability depending on locality or year of collection. We aim to analyse seed viability, among others, by investigation of the percentage of alive, dying, and dead cells in embryos and endosperm when comparing the seeds from a wild lowland population and ex situ cultivation of plants of lowland and Alpine origin. The cell death was detected by staining with two fluorescence probes, one penetrating only the changed nuclear membranes, the other penetrating also the unchanged cells. 54.5% of Alpine origin seeds were presumably capable of germination if they were sown after collection, however, four months later only 36.4% had healthy embryos. In the case of lowland wild plants it was 31.8% and 18.2%, and from ex situ, 27.3% and 13.6%, respectively. 27.3% of Alpine origin seeds had embryo in torpedo stage (9.1% in the case of lowland seeds). Mean weight of the former was 2.9 mg (2.0 mg in lowland ones). Our results confirm the significance of seed origin and seed weight on viability, and that Pulsatilla seeds have a short ‘germination time window’.
Enigmatic tracks of solitary sauropods roaming an extensive lacustrine megatracksite in Iberia
Authors: Torcida Fernández-Baldor Fidel , Díaz-Martínez I. , Huerta P. , Montero Huerta D. , Castanera D.
Published: August 2021

Sauropod remains are abundant on the Iberian Peninsula across the Jurassic-Cretaceous transition. Where the osteological record shows a high diversity of this kind of dinosaur, the ichnological findings are mainly limited to sauropod tracks characterized by kidney-shaped manus (with or without pollex impressions) and pes impressions with three claw imprints oriented laterally. Here, we present a new sauropod ichnotaxon,Iniestapodus burgensis, found at several exposures within the Las Sereas megatracksite (Burgos, Spain). These are preserved within lacustrine limestone strata of the Rupelo Formation (Tithonian–Berriasian).Iniestapodus burgensisis characterized by: semicircular manus tracks with small pollex impressions; unusual tetradactyl pes tracks with evidence of four claws oriented anteriorly (I–II) and laterally (III–IV), of variable sizes (short claw I and IV impressions, claw II and III being the largest). The combination of features and comparison with the osteological record allows us to propose a non-titanosaurian titanosauriform as a possible trackmaker. All theIniestapodustracks are represented by at least two different size classes of small and medium-sized individuals, and their trackways show different multidirectional orientations. The paleoenvironmental and paleoecological data suggest thatIniestapodustrackmakers were solitary individuals, likely representing different age classes, that crossed and used the Las Sereas shallow lacustrine-palustrine areas as their preferred habitat.
Joint temporal trends in river thermal and hydrological conditions can threaten the downstream migration of the critically endangered European eel
Authors: Arevalo Elorri , Drouineau Hilaire , Tétard Stéphane , Durif Caroline M. F. , Diserud Ola H. , Poole W. Russell , Maire Anthony
Published: August 2021

Climate change is modifying the hydrological and thermal regimes of rivers worldwide, threatening the triggering of organisms’ key life-cycle processes. European eel (Anguilla anguilla) is a critically endangered fish species that migrates over several thousand kilometres between its rearing habitats in continental waters of Europe and North Africa and its spawning area in the Sargasso Sea. Downstream migration of adult eels occurs during periods of decreasing river water temperature associated with high discharge but changes in these environmental cues may affected eel migratory conditions. An innovative multivariate method was developed to analyse long-term datasets of daily water temperature, discharge and eel passage in two European rivers. Over the past 50 years, water temperature and discharge increased in both rivers during the downstream migration period from August to November. Silver eels preferentially migrated at temperatures between 10 and 20 °C combined with high discharge. Environmental changes have resulted in the migration of silver eels under warmer water temperatures. This example illustrates how the changes in environmental cues have led to a growing mismatch between the migratory conditions preferentially selected and those actually used, which may threaten the completion of the eel’s life cycle and ultimately the persistence of this already critically endangered species.
Acircularity and circularity indexes of the foveal avascular zone in high myopia
Authors: Piao Helong , Guo Yue , Zhang Haowei , Sung Mi Sun , Park Sang Woo
Published: August 2021

This study explored the association between foveal avascular zone (FAZ) parameters and high myopia using optical coherence tomography angiography. We divided 106 eyes of 106 patients into quartiles based on the axial length. The upper quartile was then defined as the high myopia group (n = 27), while the lower quartile was the non-high myopia group (n = 26). The areas and minor axis lengths of superficial and deep FAZ, the perimeters and major axis lengths of deep FAZ were significantly larger in eyes with high myopia than in eyes with non-high myopia (P < 0.05). Inversely, the subfoveal choroidal thickness was significantly thinner in eyes with high myopia than in those with non-high myopia. Linear regression analyses showed that no significant correlation was observed between FAZ areas and acircularity and circularity indexes of FAZ in non-high myopia group. Conversely, FAZ areas strongly correlated with acircularity and circularity indexes of FAZ in high myopia group. We found that an increase in the FAZ area in highly myopic eyes was accompanied by a significant variation in FAZ acircularity and circularity indexes. Further research should address whether these findings are associated with future disease development in highly myopic eyes.
Phenotyping spinal abnormalities in patients with Neurofibromatosis type 1 using whole-body MRI
Authors: Well Lennart , Careddu Anna , Stark Maria , Farschtschi Said , Bannas Peter , Adam Gerhard , Mautner Victor-Felix , Salamon Johannes
Published: August 2021

Neurofibromatosis Type 1 (NF1) has been reported to be associated with a variety of spinal abnormalities. The purpose of this study was to quantify the prevalence of spinal abnormalities in a collective of NF1 patients that is representative for the general NF1 population, to associate the co-appearance of spinal abnormalities with both NF1 and clinical symptoms and to investigate if different mutations of the NF1 gene affect the prevalence of these abnormalities. Retrospectively, 275 patients with NF1 and an age- and sex-matched collective of 262 patients were analyzed. The prevalence of spinal abnormalities was recorded. Mutational analysis of the NF1 gene was obtained in 235 NF1 patients. Associations between spinal abnormalities, clinical symptoms and genotype were investigated by binary logistic regression analysis. Prevalence of all spinal abnormalities was higher in NF1 patients than in the control group. Six characteristics of spinal abnormalities were significantly associated with NF1 (all p < 0.05). An influence of scalloping on scoliosis (OR 3.01; p = 0.002); of meningoceles (OR 7.63) and neuroforaminal tumors (OR 2.96) on scalloping, and of dural ectasia on neuroforaminal tumors (OR 1.93) was identified. Backpain and loss of motor function were associated with neuroforaminal tumors, spinal tumors and scalloping of vertebral bodies (all p < 0.05). Specific mutations of the NF1 gene were not relevantly associated with the development of spinal abnormalities. These findings can aid clinicians to improve clinical care of NF1 patients by creating awareness for co-appearences of specific spinal abnormalities and associated symptoms.
Authenticity control of pine sylvestris essential oil by chiral gas chromatographic analysis of α-pinene
Authors: Allenspach Martina , Valder Claudia , Flamm Daniela , Steuer Christian
Published: August 2021

Numerous terpenes present in essential oils (EOs) display one or more chiral centers. Within the same genus the enantiomeric ratio of these compounds can be different. Thus, the determination of enantiomers is a valuable tool to evaluate authenticity and quality of EOs. In here, the terpene profile of primary and commercial pine EOs was analyzed by conventional and chiral gas chromatography coupled to a flame ionization detector. The enantiomeric excess of ( ±)-α-pinene was determined and significant differences between primary and commercially available EOs were observed. Primary EOs of Pinus sylvestris L. showed a positive enantiomeric excess of (+)-α-pinene whereas commercial EOs labeled as P. sylvestris L. exhibited an enantiomeric excess of (−)-α-pinene. Thus, chiral analysis provides useful information on the authenticity of pine EOs and allows to uncover possible mislabeling, the use of the wrong herbal substance and sources of adulteration in pine oil.
Improving the sustainability of biodiesel by using imidazolium-based ionic liquid
Authors: Deyab M. A. , Mohsen Q.
Published: August 2021

Corrosion of biodiesel-filled fuel tanks has become a major problem in the use of biodiesel as a new green energy source. The ionic liquid 1-Hexyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide [C10H19N2]+[C2F6NO4S2]− was used to control corrosion of C-steel in non-edible biodiesel to resolve this problem. The anti-corrosion and antioxidant properties of the [C10H19N2]+[C2F6NO4S2]− were characterized using weight loss, electrochemical impedance spectroscopy, total acid number measurements beside SEM and EDX analysis. The findings show that [C10H19N2]+[C2F6NO4S2]− plays an important role in preventing C-steel corrosion in biodiesel with an efficiency close to 99 percent. The adsorption capability and antioxidant properties of [C10H19N2]+[C2F6NO4S2]− are the major contributors to the ionic liquid's anti-corrosion properties. We anticipate that this work will help to sustainable expand the use of biodiesel as a renewable energy source.