bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linear Modeling of Spectra of Fine Particulate Materials: Implications for Compositional Analyses of Primitive Asteroids
Authors: Lowry Vanessa C. , Donaldson Hanna Kerri L. , Campins Humberto , Bowles Neil , Hamilton Victoria E. , Brown Eloïse C. 
Published: March 2022

AbstractIn this study, we applied a sum to one constraint weighted least squares (STO WLS) model to thermal infrared (TIR) spectra of a suite of primitive asteroid analogs spectrally and volumetrically dominated by fine particulates (<38 μm). Since coarse particulate emissivity spectra combine linearly, deriving compositions from these are fairly straightforward. Across the TIR it is not as straightforward for fine particulate emissivity spectra due to the nonlinear behavior that arises from volumetric scattering between particles when the particle size becomes comparable to the wavelength of light. Using a WLS model, mixed spectra may be deconvolved into areal percentages of each end member which we assume corresponds to their volume percentages. We used a spectral library of pure mineral spectra to model TIR spectra of a suite of physical mixtures and meteorites obtained under ambient (Earth‐like) and simulated asteroid environment (SAE) conditions collected for the OSIRIS‐REx team (Donaldson Hanna et al., 2021, https://doi.org/10.1029/2020JE006624). The STO WLS model underestimated the modal abundances of the dominant mineral phases by ∼25.0 ± 0.1% on average over the full spectral range and ∼22.0 ± 0.4% over a limited spectral range in all of the ambient and SAE physical mixture and meteorite spectra. Minor phases present in the mixtures and meteorites (abundances ≤5%) were typically not modeled. Also, phases not present in the mixtures were commonly selected (∼2 phases on average with an average abundance of ∼25.2 ± 1.9%) to get the best mathematical fit.
Block Kinematics in North China From GPS Measurements
Authors: Wang Wei , Zhao Bin , Qiao Xuejun , Ding Kaihua 
Published: March 2022

AbstractThe North China Craton (NCC) is an important tectonic element in China, which is characterized by intense seismic activity and complex tectonic setting. Thus quantifying its deformation is essential for studying the tectonic processes and deformation mechanisms in this region. Here we use a combination of dense GPS data sets to analyze the crustal movement and present updated estimates of fault motions based on elastic block models. We uncover spatial variations in deformation patterns, indicating that different mechanisms may dominate the tectonic processes for different parts of the NCC. In the western part, the rifts around the Ordos block manifest strike‐slip and extensional deformation, and the strike‐slip motion is more significant than the extensional component; whereas in the east, the Tanlu fault experiences right‐lateral and shortening slips, consistent with the features from historical seismic activity and regional tectonics. Our analysis indicates that the deformation in the eastern NCC is principally influenced by the Pacific subduction, whereas the deformation in the western NCC is mainly related to the India‐Eurasia collision. Moreover, our estimate of motion along the Tanlu fault supports a relatively long seismic interval of ∼10 ka, comparable to those inferred from recent paleoseismic research on this fault and other slow‐slip faults in the NCC. Our study indicates that the faults in the NCC even with very slow motions may still have the potential to produce strong earthquakes. Thus seismic risks across these slow‐slip faults cannot be ignored and should not be determined solely based on the rate of fault motions.
Hydrothermal Exploration of the Southern Chile Rise: Sediment‐Hosted Venting at the Chile Triple Junction
Authors: German C. R. , Baumberger T. , Lilley M. D. , Lupton J. E. , Noble A. E. , Saito M. , Thurber A. R. , Blackman D. K. 
Published: March 2022

AbstractWe report results from a hydrothermal plume survey along the southernmost Chile Rise from the Guamblin Fracture Zone to the Chile Triple Junction (CTJ) encompassing two segments (93 km cumulative length) of intermediate spreading‐rate mid‐ocean ridge axis. Our approach used in situ water column sensing (CTD, optical clarity, redox disequilibrium) coupled with sampling for shipboard and shore based geochemical analyses (δ3He, CH4, total dissolvable iron (TDFe) and manganese, (TDMn)) to explore for evidence of seafloor hydrothermal venting. Across the entire survey, the only location at which evidence for submarine venting was detected was at the southernmost limit to the survey. There, the source of a dispersing hydrothermal plume was located at 46°16.5’S, 75°47.9’W, coincident with the CTJ itself. The plume exhibits anomalies in both δ3He and dissolved CH4 but no enrichments in TDFe or TDMn beyond what can be attributed to resuspension of sediments covering the seafloor where the ridge intersects the Chile margin. These results are indicative of sediment‐hosted venting at the CTJ.
Southern China Winter Rainfall Modulated by South China Sea Warming
Authors: Wang Qiang , Zhong Wenxiu , Yang Song , Wang Junbin , Zeng Lili , Chen Ju , He Yunkai 
Published: March 2022

AbstractNew insight into the contribution of anomalous South China Sea (SCS) warming is proposed to understand strong southern China (SC) winter rainfall. El Niño events, which weaken the East Asian winter monsoon (EAWM), favor SC winter rainfall. However, the changes in SC winter rainfall are not always in phase with the El Niño‐Southern Oscillation, making the prediction of East Asian climate challenging. Here, we show that the increased moisture associated with the warming SCS induced by the weakening western boundary current leads to increased meridional moisture transport to SC. Particularly, during the El Niño mature winter phase, this effect works jointly with a weakened EAWM to determine an increased rainfall over SC. Therefore, we suggest that the thermal state of the SCS should be considered when large‐scale tropical ocean‐atmosphere variability is utilized to predict SC winter rainfall.
Dopamine transporter silencing in the rat: systems-level alterations in striato-cerebellar and prefrontal-midbrain circuits
Authors: Reinwald Jonathan R. , Gass Natalia , Mallien Anne S. , Sartorius Alexander , Becker Robert , Sack Markus , Falfan-Melgoza Claudia , Clemm von Hohenberg Christian , Leo Damiana , Pfeiffer Natascha , Middelman Anthonieke , Meyer-Lindenberg Andreas , Homberg Judith R. , Weber-Fahr Wolfgang , Gass Peter 
Published: March 2022

AbstractSilencing of dopamine transporter (DAT), a main controlling factor of dopaminergic signaling, results in biochemical and behavioral features characteristic for neuropsychiatric diseases with presumed hyperdopaminergia including schizophrenia, attention deficit hyperactivity disorder (ADHD), bipolar disorder, and obsessive-compulsive disorder (OCD). Investigation of DAT silencing thus provides a transdiagnostic approach towards a systems-level understanding of common underlying pathways. Using a high-field multimodal imaging approach and a highly sensitive cryogenic coil, we integrated structural, functional and metabolic investigations in tandem with behavioral assessments on a newly developed preclinical rat model, comparing DAT homozygous knockout (DAT-KO, N = 14), heterozygous knockout (N = 8) and wild-type male rats (N = 14). We identified spatially distributed structural and functional brain alterations encompassing motor, limbic and associative loops that demonstrated strong behavioral relevance and were highly consistent across imaging modalities. DAT-KO rats manifested pronounced volume loss in the dorsal striatum, negatively correlating with cerebellar volume increase. These alterations were associated with hyperlocomotion, repetitive behavior and loss of efficient functional small-world organization. Further, prefrontal and midbrain regions manifested opposite changes in functional connectivity and local network topology. These prefrontal disturbances were corroborated by elevated myo-inositol levels and increased volume. To conclude, our imaging genetics approach provides multimodal evidence for prefrontal-midbrain decoupling and striato-cerebellar neuroplastic compensation as two key features of constitutive DAT blockade, proposing them as transdiagnostic mechanisms of hyperdopaminergia. Thus, our study connects developmental DAT blockade to systems-level brain changes, underlying impaired action inhibition control and resulting in motor hyperactivity and compulsive-like features relevant for ADHD, schizophrenia and OCD.
miR-146a impedes the anti-aging effect of AMPK via NAMPT suppression and NAD+/SIRT inactivation
Authors: Gong Hui , Chen Honghan , Xiao Peng , Huang Ning , Han Xiaojuan , Zhang Jian , Yang Yu , Li Tiepeng , Zhao Tingting , Tai Haoran , Xu Weitong , Zhang Gongchang , Gong Chuhui , Yang Ming , Tang Xiaoqiang , Xiao Hengyi 
Published: March 2022

AbstractNicotinamide adenine dinucleotide (NAD+) is indispensable for the anti-aging activity of the sirtuin (SIRT) family enzymes. AMP-activated protein kinase (AMPK) upregulates NAD+ synthesis and SIRT activity in a nicotinamide phosphoribosyltransferase (NAMPT)-dependent manner. However, the molecular mechanisms that affect AMPK-driven NAMPT expression and NAD+/SIRT activation remain unclear. In this study, we tried to identify senescence-associated microRNAs (miRNAs) that negatively regulate the cascade linking AMPK and NAMPT expression. miRNA-screening experiments showed that the expression of miR-146a increased in senescent cells but decreased following AMPK activation. Additionally, miR-146a overexpression weakened the metformin-mediated upregulation of NAMPT expression, NAD+ synthesis, SIRT activity, and senescence protection, whereas treatment with the miR-146a inhibitor reversed this effect. Importantly, these findings were observed both in vitro and in vivo. Mechanistically, miR-146a directly targeted the 3′-UTR of Nampt mRNA to reduce the expression of NAMPT. AMPK activators metformin and 5-aminoimidazole-4-carboxamide (AICAR) hindered miR-146a expression at the transcriptional level by promoting IκB kinase (IKK) phosphorylation to attenuate nuclear factor-kappaB (NF-κB) activity. These findings identified a novel cascade that negatively regulates the NAD+/SIRT pathway by suppressing miR-146a-mediated NAMPT downregulation. Furthermore, our results showed that miR-146a impedes the anti-aging effect of AMPK. This mutual inhibitory relationship between miR-146a and AMPK enriches our understanding of the molecular connections between AMPK and SIRT and provides new insight into miRNA-mediated NAD+/SIRT regulation and an intervention point for the prevention of aging and age-related diseases.
Stress vulnerability shapes disruption of motor cortical neuroplasticity
Authors: Gellner Anne-Kathrin , Sitter Aileen , Rackiewicz Michal , Sylvester Marc , Philipsen Alexandra , Zimmer Andreas , Stein Valentin 
Published: March 2022

AbstractChronic stress is a major cause of neuropsychiatric conditions such as depression. Stress vulnerability varies individually in mice and humans, measured by behavioral changes. In contrast to affective symptoms, motor retardation as a consequence of stress is not well understood. We repeatedly imaged dendritic spines of the motor cortex in Thy1-GFP M mice before and after chronic social defeat stress. Susceptible and resilient phenotypes were discriminated by symptom load and their motor learning abilities were assessed by a gross and fine motor task. Stress phenotypes presented individual short- and long-term changes in the hypothalamic–pituitary–adrenal axis as well as distinct patterns of altered motor learning. Importantly, stress was generally accompanied by a marked reduction of spine density in the motor cortex and spine dynamics depended on the stress phenotype. We found astrogliosis and altered microglia morphology along with increased microglia-neuron interaction in the motor cortex of susceptible mice. In cerebrospinal fluid, proteomic fingerprints link the behavioral changes and structural alterations in the brain to neurodegenerative disorders and dysregulated synaptic homeostasis. Our work emphasizes the importance of synaptic integrity and the risk of neurodegeneration within depression as a threat to brain health.
Edonerpic maleate regulates glutamate receptors through CRMP2- and Arc-mediated mechanisms in response to brain trauma
Authors: Chen Tao , Yang Li-Kun , Ai Pu , Zhu Jie , Hang Chun-Hua , Wang Yu-Hai 
Published: March 2022

AbstractDysfunction of ionotropic glutamate receptors (iGluRs) is a key molecular mechanism of excitotoxic neuronal injury following traumatic brain injury (TBI). Edonerpic maleate is a low molecular-weight compound that was screened as a candidate neuroprotective agent. In this study, we investigated its effects on TBI and GluRs signaling. Traumatic neuronal injury (TNI) induced by scratch followed by glutamate treatment was performed to mimic TBI in vitro. Edonerpic maleate at 1 and 10 μM exerted protective activity when it was added within 2 h following injury. The protective activities were also confirmed by the reduction of lipid peroxidation and oxidative stress. In addition, edonerpic maleate inhibited the expression of surface NR2B, total GluR1, and surface GluR1, and mitigated the intracellular Ca2+ responses following injury in vitro. Western blot analysis showed that edonerpic maleate reduced the cleavage of collapsing response mediator protein 2 (CRMP2), but increased the expression of postsynaptic protein Arc. By using gene overexpression and silencing technologies, CRMP2 was overexpressed and Arc was knockdown in cortical neurons. The results showed that the effect of edonerpic maleate on NMDA receptor expression was mediated by CRMP2, whereas the edonerpic maleate-induced AMPA receptor regulation was dependent on Arc activation. In in vivo TBI model, 30 mg/kg edonerpic maleate alleviated the TBI-induced brain edema, neuronal loss, and microglial activation, with no effect on locomotor function at 24 h. However, edonerpic maleate improves long-term neurological function after TBI. Furthermore, edonerpic maleate inhibited CRMP2 cleavage but increased Arc activation in vivo. In summary, our results identify edonerpic maleate as a clinically potent small compound with which to attenuate TBI-related brain damage through regulating GluRs signaling.
In vitro maturation of Toxoplasma gondii bradyzoites in human myotubes and their metabolomic characterization
Authors: Christiansen Céline , Maus Deborah , Hoppenz Ellen , Murillo-León Mateo , Hoffmann Tobias , Scholz Jana , Melerowicz Florian , Steinfeldt Tobias , Seeber Frank , Blume Martin 
Published: March 2022

AbstractThe apicomplexan parasiteToxoplasma gondiiforms bradyzoite-containing tissue cysts that cause chronic and drug-tolerant infections. However, current in vitro models do not allow long-term culture of these cysts to maturity. Here, we developed a human myotube-based in vitro culture model of functionally mature tissue cysts that are orally infectious to mice and tolerate exposure to a range of antibiotics and temperature stresses. Metabolomic characterization of purified cysts reveals global changes that comprise increased levels of amino acids and decreased abundance of nucleobase- and tricarboxylic acid cycle-associated metabolites. In contrast to fast replicating tachyzoite forms ofT. gondiithese tissue cysts tolerate exposure to the aconitase inhibitor sodium fluoroacetate. Direct access to persistent stages ofT. gondiiunder defined cell culture conditions will be essential for the dissection of functionally important host-parasite interactions and drug evasion mechanisms. It will also facilitate the identification of new strategies for therapeutic intervention.
Structural insight into Marburg virus nucleoprotein–RNA complex formation
Authors: Fujita-Fujiharu Yoko , Sugita Yukihiko , Takamatsu Yuki , Houri Kazuya , Igarashi Manabu , Muramoto Yukiko , Nakano Masahiro , Tsunoda Yugo , Taniguchi Ichiro , Becker Stephan , Noda Takeshi 
Published: March 2022

AbstractThe nucleoprotein (NP) of Marburg virus (MARV), a close relative of Ebola virus (EBOV), encapsidates the single-stranded, negative-sense viral genomic RNA (vRNA) to form the helical NP–RNA complex. The NP–RNA complex constitutes the core structure for the assembly of the nucleocapsid that is responsible for viral RNA synthesis. Although appropriate interactions among NPs and RNA are required for the formation of nucleocapsid, the structural basis of the helical assembly remains largely elusive. Here, we show the structure of the MARV NP–RNA complex determined using cryo-electron microscopy at a resolution of 3.1 Å. The structures of the asymmetric unit, a complex of an NP and six RNA nucleotides, was very similar to that of EBOV, suggesting that both viruses share common mechanisms for the nucleocapsid formation. Structure-based mutational analysis of both MARV and EBOV NPs identified key residues for helical assembly and subsequent viral RNA synthesis. Importantly, most of the residues identified were conserved in both viruses. These findings provide a structural basis for understanding the nucleocapsid formation and contribute to the development of novel antivirals against MARV and EBOV.
The control of transcriptional memory by stable mitotic bookmarking
Authors: Bellec Maëlle , Dufourt Jérémy , Hunt George , Lenden-Hasse Hélène , Trullo Antonio , Zine El Aabidine Amal , Lamarque Marie , Gaskill Marissa M. , Faure-Gautron Heloïse , Mannervik Mattias , Harrison Melissa M. , Andrau Jean-Christophe , Favard Cyril , Radulescu Ovidiu , Lagha Mounia 
Published: March 2022

AbstractTo maintain cellular identities during development, gene expression profiles must be faithfully propagated through cell generations. The reestablishment of gene expression patterns upon mitotic exit is mediated, in part, by transcription factors (TF) mitotic bookmarking. However, the mechanisms and functions of TF mitotic bookmarking during early embryogenesis remain poorly understood. In this study, taking advantage of the naturally synchronized mitoses ofDrosophilaearly embryos, we provide evidence that GAGA pioneer factor (GAF) acts as a stable mitotic bookmarker during zygotic genome activation. We show that, during mitosis, GAF remains associated to a large fraction of its interphase targets, including atcis-regulatory sequences of key developmental genes with both active and repressive chromatin signatures. GAF mitotic targets are globally accessible during mitosis and are bookmarked via histone acetylation (H4K8ac). By monitoring the kinetics of transcriptional activation in living embryos, we report that GAF binding establishes competence for rapid activation upon mitotic exit.
A comprehensive WGS-based pipeline for the identification of new candidate genes in inherited retinal dystrophies
Authors: González-del Pozo María , Fernández-Suárez Elena , Bravo-Gil Nereida , Méndez-Vidal Cristina , Martín-Sánchez Marta , Rodríguez-de la Rúa Enrique , Ramos-Jiménez Manuel , Morillo-Sánchez María José , Borrego Salud , Antiñolo Guillermo 
Published: March 2022

AbstractTo enhance the use of Whole Genome Sequencing (WGS) in clinical practice, it is still necessary to standardize data analysis pipelines. Herein, we aimed to define a WGS-based algorithm for the accurate interpretation of variants in inherited retinal dystrophies (IRD). This study comprised 429 phenotyped individuals divided into three cohorts. A comparison of 14 pathogenicity predictors, and the re-definition of its cutoffs, were performed using panel-sequencing curated data from 209 genetically diagnosed individuals with IRD (training cohort). The optimal tool combinations, previously validated in 50 additional IRD individuals, were also tested in patients with hereditary cancer (n = 109), and with neurological diseases (n = 47) to evaluate the translational value of this approach (validation cohort). Then, our workflow was applied for the WGS-data analysis of 14 individuals from genetically undiagnosed IRD families (discovery cohort). The statistical analysis showed that the optimal filtering combination included CADDv1.6, MAPP, Grantham, and SIFT tools. Our pipeline allowed the identification of one homozygous variant in the candidate gene CFAP20 (c.337 C > T; p.Arg113Trp), a conserved ciliary gene, which was abundantly expressed in human retina and was located in the photoreceptors layer. Although further studies are needed, we propose CFAP20 as a candidate gene for autosomal recessive retinitis pigmentosa. Moreover, we offer a translational strategy for accurate WGS-data prioritization, which is essential for the advancement of personalized medicine.
Generation of nonlinearity in the electrical response of yeast suspensions
Authors: Tamura K. , Muraji M. , Tanaka K. , Shirafuji T. 
Published: March 2022

AbstractThe mechanism through which nonlinearity is generated in the response waveform of the electric current obtained by applying alternating current voltage to yeast suspension has not yet been elucidated. In this paper, we showed that the response waveform depends on the applied voltage and frequency. The results showed that distortion (nonlinearity) in the waveform increases as the applied voltage increases and/or the frequency decreases. We suggest a model for the generation of nonlinearity based on the influx of potassium ions into the cell via potassium ion channels and transporters in the membrane due to the applied voltage. Furthermore, we validated this model by simulating an electrical circuit.
Modular polymer platform as a novel approach to head and neck cancer therapy
Authors: Alhiyari Yazeed , Shao Jundong , Han Albert Y. , Miller Amanda , Krane Jeffrey F. , Luff Marie , Momcilovic Milica , Shackelford David , Gu Zhen , John Maie A. St. 
Published: March 2022

AbstractHead and neck cancer is the sixth most common cancer in the world, with more than 300,000 deaths attributed to the disease annually. Aggressive surgical resection often with adjuvant chemoradiation is the cornerstone of treatment. However, the necessary chemoradiation treatment can result in collateral damage to adjacent vital structures causing a profound impact on quality of life. Here, we present a novel polymer of poly(lactic-co-glycolic) acid and polyvinyl alcohol that can serve as a versatile multidrug delivery platform as well as for detection on cross-sectional imaging while functioning as a fiduciary marker for postoperative radiotherapy and radiotherapeutic dosing. In a mouse xenograft model, the dual-layered polymer composed of calcium carbonate/thymoquinone was used for both polymer localization and narrow-field infusion of a natural therapeutic compound. A similar approach can be applied in the treatment of head and neck cancer patients, where immunotherapy and traditional chemotherapy can be delivered simultaneously with independent release kinetics.