bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractThe 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

AbstractThis 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

AbstractHumans 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

Abstract
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

AbstractIndividuals 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

AbstractWe 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

AbstractPrevious 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

AbstractTo 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

AbstractThe 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

AbstractProgranulin (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

AbstractPulsatilla 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

AbstractSauropod 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

AbstractClimate 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

AbstractThis 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.