bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Importance of Electron Landau Damping for the Dissipation of Turbulent Energy in Terrestrial Magnetosheath Plasma
Authors: Afshari A. S. , Howes G. G. , Kletzing C. A. , Hartley D. P. , Boardsen S. A. 
Published: December 2021

AbstractHeliospheric plasma turbulence plays a key role in transferring the energy of large‐scale magnetic field and plasma flow fluctuations to smaller scales where the energy can be dissipated, ultimately leading to plasma heating. High‐quality measurements of electromagnetic fields and electron velocity distributions by the Magnetospheric Multiscale (MMS) mission in Earth's magnetosheath present a unique opportunity to characterize plasma turbulence and to determine the mechanisms responsible for its dissipation. We apply the field‐particle correlation technique to a set of 20 MMS magnetosheath intervals to identify the dissipation mechanism and quantify the dissipation rate. It is found that 95% of the intervals have velocity‐space signatures of electron Landau damping that are quantitatively consistent with linear kinetic theory for the collisionless damping of kinetic Alfvén waves. About 75% of the intervals contain asymmetric signatures, indicating a local imbalance of kinetic Alfvén wave energy flux in one direction along the magnetic field than the other. About one‐third of the intervals have an electron energization rate with the same order‐of‐magnitude as the estimated turbulent cascade rate, suggesting that electron Landau damping plays a significant, and sometimes dominant, role in the dissipation of the turbulent energy in these magnetosheath intervals.
The Interaction Between Warm‐Core Rings and Submarine Canyons and Its Influence on the Onshore Transport of Offshore Waters
Authors: Li Xiaodan , Zhang Weifeng (Gordon) , Rong Zengrui 
Published: December 2021

AbstractGulf Stream warm‐core rings (WCRs) impinging onto the Mid‐Atlantic Bight (MAB) shelf edge can induce substantial water exchange between the shelf and slope seas. Combining satellite imagery and idealized ocean models, this study investigates the long‐neglected influence of submarine canyons on the WCR impingement process. Satellite images show onshore intrusion of the WCR water concentrated near the MAB shelf‐break canyons, indicating canyon‐induced enhancement of cross‐shelf exchange. Model simulations of the ring‐canyon interaction qualitatively reproduce the observed pattern and show greatly enhanced vertical motions and cross‐shelf transport in a canyon. The ring‐induced transient flow in a canyon resolved by the model is consistent with the three‐dimensional canyon circulation driven by ambient along‐slope steady flows as depicted in the literature. Cross‐isobath flows occur over both canyon slopes with a strong upwelling onshore flow over the slope upstream to the coastal‐trapped wave propagation (the upwave slope) and a weak downwelling offshore flow over the downwave slope. To conserve potential vorticity, a subsurface‐intensified cyclonic eddy is formed inside the canyon, which interacts with the sloping bottom and enhances the upwelling onshore flow over the upwave slope. The upwelled deep ring water is transported either back offshore by the ring‐edge current on the upwave side of the canyon or across the canyon onto the downwave shelf forming a localized bulge pattern. While the former is an ephemeral onshore transport process, the latter represents a more sustained onshore transport of the ring water, both of which have major implication for ecosystem dynamics at the shelf edge.
Origin of the Intra‐Oceanic Silverwood Block (New England Orogen, Australia): Evidence From Radiolarian Biostratigraphy and Detrital Zircon Petrochronology
Authors: Rosenbaum Gideon , Rogers Ashley , Gürer Derya , Andjić Goran , Allen Charlotte M. 
Published: December 2021

AbstractCambrian to Triassic subduction processes in eastern Australia produced a complex and highly contorted assembly of supra‐subduction units. However, regardless of the long history of oceanic subduction, relatively little evidence exists on oceanic terranes whose accretion onto the continental margin may have accompanied subduction processes. We present new radiolarian and petrochronological data from Devonian and Carboniferous rocks exposed in the middle of a tight orocline. Based on radiolarian biostratigraphy and U‐Pb dating of detrital zircon grains, we show that volcaniclastic rocks from the Silverwood Group and Alice Creek beds were deposited during the Late Devonian, which is later than previously thought. Trace‐element compositions of the Devonian zircons are characteristic of crystallization of magmas in an oceanic environment, thus supporting previous suggestions that the Silverwood Group was derived from an intra‐oceanic arc system. Carboniferous zircons from a nearby forearc basin unit (Mount Barney beds) exhibit a continental affinity, indicating that accretion of the Silverwood Block likely occurred before the establishment of this continental arc. A serpentinite belt that occurs adjacent to the Silverwood Block might represent a remnant ophiolitic suture of the now‐consumed oceanic domain, which once separated the Silverwood Block from the eastern Gondwanan margin. Based on the assumption that such an intervening ocean existed, we discuss alternative scenarios for the origin and accretion of the Silverwood Block. The most likely scenario involves intra‐oceanic magmatism in a marginal oceanic basin whose development was driven by trench retreat, and a subsequent accretion in response to trench advance and/or slab flattening.
Stochastic Inversion of Three‐Dimensional Discrete Fracture Network Structure With Hydraulic Tomography
Authors: Ringel Lisa Maria , Jalali Mohammadreza , Bayer Peter 
Published: December 2021

AbstractWe introduce an approach for the stochastic characterization of the geometric and hydraulic parameters of a three‐dimensional (3D) discrete fracture network (DFN) and for estimating their uncertainty based on data from hydraulic tomography experiments. The inversion approach relies on a Bayesian framework and the resulting posterior distribution is characterized by generating samples by Markov chain Monte Carlo (MCMC) methods. The inversion method is evaluated for four synthetic test cases related to the Grimsel test site in Switzerland. Comparison of original and reconstructed DFN models shows that the presented approach is suitable for identifying variable fracture locations and orientations. This is especially the case for those fractures that represent the preferential flow paths in the simulated experiments. It is also revealed that the Bayesian framework is useful to discriminate fractures based on the reliability of the inversion, which is illustrated by fracture probability maps taken as sections through the studied rock mass. Moreover, it is demonstrated that the hydraulic apertures can be calibrated together with the fracture geometries. A premise for applicability in practice, however, is that the hydraulic measurements are complemented by additional information to sufficiently constrain the value ranges of the geometric and hydraulic parameters to be inverted together. The presented work expands the applicability of a previously presented promising two‐dimensional procedure based on transdimensional inversion to field‐based 3D problems. The theoretical findings here open the door for highly flexible structural characterization in practice based on hydraulic tomography, as well as alternative or complementary tomographic methods.
Gab2 deficiency prevents Flt3-ITD driven acute myeloid leukemia in vivo
Authors: Spohr Corinna , Poggio Teresa , Andrieux Geoffroy , Schönberger Katharina , Cabezas-Wallscheid Nina , Boerries Melanie , Halbach Sebastian , Illert Anna L. , Brummer Tilman 
Published: December 2021

AbstractInternal tandem duplications (ITD) of the FMS-like tyrosine kinase 3 (FLT3) predict poor prognosis in acute myeloid leukemia (AML) and often co-exist with inactivating DNMT3A mutations. In vitro studies implicated Grb2-associated binder 2 (GAB2) as FLT3-ITD effector. Utilizing a Flt3-ITD knock-in, Dnmt3a haploinsufficient mouse model, we demonstrate that Gab2 is essential for the development of Flt3-ITD driven AML in vivo, as Gab2 deficient mice displayed prolonged survival, presented with attenuated liver and spleen pathology and reduced blast counts. Furthermore, leukemic bone marrow from Gab2 deficient mice exhibited reduced colony-forming unit capacity and increased FLT3 inhibitor sensitivity. Using transcriptomics, we identify the genes encoding for Axl and the Ret co-receptor Gfra2 as targets of the Flt3-ITD/Gab2/Stat5 axis. We propose a pathomechanism in which Gab2 increases signaling of these receptors by inducing their expression and by serving as downstream effector. Thereby, Gab2 promotes AML aggressiveness and drug resistance as it incorporates these receptor tyrosine kinases into the Flt3-ITD signaling network. Consequently, our data identify GAB2 as a promising biomarker and therapeutic target in human AML.
Mammalian gut metabolomes mirror microbiome composition and host phylogeny
Authors: Gregor Rachel , Probst Maraike , Eyal Stav , Aksenov Alexander , Sasson Goor , Horovitz Igal , Dorrestein Pieter C , Meijler Michael M , Mizrahi Itzhak 
Published: December 2021

Abstract
In the past decade, studies on the mammalian gut microbiome have revealed that different animal species have distinct gut microbial compositions. The functional ramifications of this variation in microbial composition remain unclear: do these taxonomic differences indicate microbial adaptations to host-specific functionality, or are these diverse microbial communities essentially functionally redundant, as has been indicated by previous metagenomics studies? Here, we examine the metabolic content of mammalian gut microbiomes as a direct window into ecosystem function, using an untargeted metabolomics platform to analyze 101 fecal samples from a range of 25 exotic mammalian species in collaboration with a zoological center. We find that mammalian metabolomes are chemically diverse and strongly linked to microbiome composition, and that metabolome composition is further correlated to the phylogeny of the mammalian host. Specific metabolites enriched in different animal species included modified and degraded host and dietary compounds such as bile acids and triterpenoids, as well as fermentation products such as lactate and short-chain fatty acids. Our results suggest that differences in microbial taxonomic composition are indeed translated to host-specific metabolism, indicating that taxonomically distant microbiomes are more functionally diverse than redundant.
Colonization of gut microbiota by plasmid-carrying bacteria is facilitated by evolutionary adaptation to antibiotic treatment
Authors: Zhang Peng , Mao Daqing , Gao Huihui , Zheng Liyang , Chen Zeyou , Gao Yuting , Duan Yitao , Guo Jianhua , Luo Yi , Ren Hongqiang 
Published: December 2021

Abstract
Multidrug-resistant plasmid-carrying bacteria are of particular clinical concern as they could transfer antibiotic resistance genes to other bacterial species. However, little is known whether evolutionary adaptation of plasmid-carrying bacteria after long-term antibiotic exposure could affect their subsequent colonization of the human gut. Herein, we combined a long-term evolutionary model based on Escherichia coli K-12 MG1655 and the multidrug-resistant plasmid RP4 with in vivo colonization experiments in mice. We found that the evolutionary adaptation of plasmid-carrying bacteria to antibiotic exposure facilitated colonization of the murine gut and subsequent plasmid transfer to gut bacteria. The evolved plasmid-carrying bacteria exhibited phenotypic alterations, including multidrug resistance, enhanced bacterial growth and biofilm formation capability and decreased plasmid fitness cost, which might be jointly caused by chromosomal mutations (SNPs in rpoC, proQ, and hcaT) and transcriptional modifications. The upregulated transcriptional genes, e.g., type 1 fimbrial-protein pilus (fimA and fimH) and the surface adhesin gene (flu) were likely responsible for the enhanced biofilm-forming capacity. The gene tnaA that encodes a tryptophanase-catalyzing indole formation was transcriptionally upregulated, and increased indole products participated in facilitating the maximum population density of the evolved strains. Furthermore, several chromosomal genes encoding efflux pumps (acriflavine resistance proteins A and B (acrA, acrB), outer-membrane protein (tolC), multidrug-resistance protein (mdtM), and macrolide export proteins A and B (macA, macB)) were transcriptionally upregulated, while most plasmid-harboring genes (conjugal transfer protein (traF) and (trbB), replication protein gene (trfA), beta-lactamase TEM precursor (blaTEM), aminoglycoside 3′-phosphotransferase (aphA) and tetracycline resistance protein A (tetA)) were downregulated. Collectively, these findings demonstrated that evolutionary adaptation of plasmid-carrying bacteria in an antibiotic-influenced environment facilitated colonization of the murine gut by the bacteria and plasmids.
Regional gray matter oligodendrocyte- and myelin-related measures are associated with differential susceptibility to stress-induced behavior in rats and humans
Authors: Long Kimberly L. P. , Chao Linda L. , Kazama Yurika , An Anjile , Hu Kelsey Y. , Peretz Lior , Muller Dyana C. Y. , Roan Vivian D. , Misra Rhea , Toth Claire E. , Breton Jocelyn M. , Casazza William , Mostafavi Sara , Huber Bertrand R. , Woodward Steven H. , Neylan Thomas C. , Kaufer Daniela 
Published: December 2021

AbstractIndividual reactions to traumatic stress vary dramatically, yet the biological basis of this variation remains poorly understood. Recent studies demonstrate the surprising plasticity of oligodendrocytes and myelin with stress and experience, providing a potential mechanism by which trauma induces aberrant structural and functional changes in the adult brain. In this study, we utilized a translational approach to test the hypothesis that gray matter oligodendrocytes contribute to traumatic-stress-induced behavioral variation in both rats and humans. We exposed adult, male rats to a single, severe stressor and used a multimodal approach to characterize avoidance, startle, and fear-learning behavior, as well as oligodendrocyte and myelin basic protein (MBP) content in multiple brain areas. We found that oligodendrocyte cell density and MBP were correlated with behavioral outcomes in a region-specific manner. Specifically, stress-induced avoidance positively correlated with hippocampal dentate gyrus oligodendrocytes and MBP. Viral overexpression of the oligodendrogenic factor Olig1 in the dentate gyrus was sufficient to induce an anxiety-like behavioral phenotype. In contrast, contextual fear learning positively correlated with MBP in the amygdala and spatial-processing regions of the hippocampus. In a group of trauma-exposed US veterans, T1-/T2-weighted magnetic resonance imaging estimates of hippocampal and amygdala myelin associated with symptom profiles in a region-specific manner that mirrored the findings in rats. These results demonstrate a species-independent relationship between region-specific, gray matter oligodendrocytes and differential behavioral phenotypes following traumatic stress exposure. This study suggests a novel mechanism for brain plasticity that underlies individual variance in sensitivity to traumatic stress.
Effects of escitalopram therapy on resting-state functional connectivity of subsystems of the default mode network in unmedicated patients with major depressive disorder
Authors: Cui Jian , Wang Yun , Liu Rui , Chen Xiongying , Zhang Zhifang , Feng Yuan , Zhou Jingjing , Zhou Yuan , Wang Gang 
Published: December 2021

AbstractAntidepressants are often the first-line medications prescribed for patients with major depressive disorder (MDD). Given the critical role of the default mode network (DMN) in the physiopathology of MDD, the current study aimed to investigate the effects of antidepressants on the resting-state functional connectivity (rsFC) within and between the DMN subsystems. We collected resting-state functional magnetic resonance imaging (rs-fMRI) data from 36 unmedicated MDD patients at baseline and after escitalopram treatment for 12 weeks. The rs-fMRI data were also collected from 61 matched healthy controls at the time point with the same interval. Then, we decomposed the DMN into three subsystems based on a template from previous studies and computed the rsFC within and between the three subsystems. Finally, repeated measures analysis of covariance was conducted to identify the main effect of group and time and their interaction effect. We found that the significantly reduced within-subsystem rsFC in the DMN core subsystem in patients with MDD at baseline was increased after escitalopram treatment and became comparable with that in the healthy controls, whereas the reduced within-subsystem rsFC persisted in the DMN dorsal medial prefrontal cortex (dMPFC) and medial temporal subsystems in patients with MDD following escitalopram treatment. In addition, the reduced between-subsystem rsFC between the core and dMPFC subsystem showed a similar trend of change after treatment in patients with MDD. Moreover, our main results were confirmed using the DMN regions from another brain atlas. In the current study, we found different effects of escitalopram on the rsFC of the DMN subsystems. These findings deepened our understanding of the neuronal basis of antidepressants’ effect on brain function in patients with MDD. The trial name: appropriate technology study of MDD diagnosis and treatment based on objective indicators and measurement. URL: http://www.chictr.org.cn/showproj.aspx?proj=21377. Registration number: ChiCTR-OOC-17012566.
Sex differences in the genetic regulation of the blood transcriptome response to glucocorticoid receptor activation
Authors: Moore Sarah R. , Halldorsdottir Thorhildur , Martins Jade , Lucae Susanne , Müller-Myhsok Bertram , Müller Nikola S. , Piechaczek Charlotte , Feldmann Lisa , Freisleder Franz Joseph , Greimel Ellen , Schulte-Körne Gerd , Binder Elisabeth B. , Arloth Janine 
Published: December 2021

AbstractSubstantial sex differences have been reported in the physiological response to stress at multiple levels, including the release of the stress hormone, cortisol. Here, we explore the genomic variants in 93 females and 196 males regulating the initial transcriptional response to cortisol via glucocorticoid receptor (GR) activation. Gene expression levels in peripheral blood were obtained before and after GR-stimulation with the selective GR agonist dexamethasone to identify differential expression following GR-activation. Sex stratified analyses revealed that while the transcripts responsive to GR-stimulation were mostly overlapping between males and females, the quantitative trait loci (eQTLs) regulation differential transcription to GR-stimulation was distinct. Sex-stratified eQTL SNPs (eSNPs) were located in different functional genomic elements and sex-stratified transcripts were enriched within postmortem brain transcriptional profiles associated with Major Depressive Disorder (MDD) specifically in males and females in the cingulate cortex. Female eSNPs were enriched among SNPs linked to MDD in genome-wide association studies. Finally, transcriptional sensitive genetic profile scores derived from sex-stratified eSNPS regulating differential transcription to GR-stimulation were predictive of depression status and depressive symptoms in a sex-concordant manner in a child and adolescent cohort (n = 584). These results suggest the potential of eQTLs regulating differential transcription to GR-stimulation as biomarkers of sex-specific biological risk for stress-related psychiatric disorders.
Faecal immunochemical test for patients with ‘high-risk’ bowel symptoms: a large prospective cohort study and updated literature review
Authors: Laszlo Helga E. , Seward Edward , Ayling Ruth M. , Lake Jennifer , Malhi Aman , Stephens Clare , Pritchard-Jones Kathy , Chung Donna , Hackshaw Allan , Machesney Michael 
Published: December 2021

AbstractBackgroundWe evaluated whether faecal immunochemical testing (FIT) can rule out colorectal cancer (CRC) among patients presenting with ‘high-risk’ symptoms requiring definitive investigation.MethodsThree thousand five hundred and ninety-six symptomatic patients referred to the standard urgent CRC pathway were recruited in a multi-centre observational study. They completed FIT in addition to standard investigations. CRC miss rate (percentage of CRC cases with low quantitative faecal haemoglobin [f-Hb] measurement) and specificity (percentage of patients without cancer with low f-Hb) were calculated. We also provided an updated literature review.ResultsNinety patients had CRC. At f-Hb < 10 µg/g, the miss rate was 16.7% (specificity 80.1%). At f-Hb < 4 µg/g, the miss rate was 12.2% (specificity 73%), which became 3.3% if low FIT plus the absence of anaemia and abdominal pain were considered (specificity 51%). Within meta-analyses of 9 UK studies, the pooled miss rate was 7.2% (specificity 74%) for f-Hb < 4 µg/g.DiscussionFIT alone as a triage tool would miss an estimated 1 in 8 cases in our study (1 in 14 from meta-analysis), while many people without CRC could avoid investigations. FIT can focus secondary care diagnostic capacity on patients most at risk of CRC, but more work on safety netting is required before incorporating FIT triage into the urgent diagnostic pathway.
The BH3-only protein NOXA serves as an independent predictor of breast cancer patient survival and defines susceptibility to microtubule targeting agents
Authors: Karbon Gerlinde , Haschka Manuel D. , Hackl Hubert , Soratroi Claudia , Rocamora-Reverte Lourdes , Parson Walther , Fiegl Heidelinde , Villunger Andreas 
Published: December 2021

AbstractBreast cancer (BC) treatment frequently involves microtubule-targeting agents (MTAs), such as paclitaxel, that arrest cells in mitosis. Sensitivity to MTAs is defined by a subset of pro- and anti-apoptotic BCL2 family proteins controlling mitochondrial apoptosis. Here, we aimed to determine their prognostic value in primary tumour samples from 92 BC patients. Our analysis identified high NOXA/PMAIP mRNA expression levels as an independent prognostic marker for improved relapse-free survival (RFS) and overall survival (OS) in multivariate analysis in BC patients, independent of their molecular subtype. Analysis of available TCGA datasets of 1060 BC patients confirmed our results and added a clear predictive value of NOXA mRNA levels for patients who received MTA-based therapy. In this TCGA cohort, 122 patients received MTA-treatment and high NOXA mRNA levels correlated with their progression-free interval (PFI) and OS. Our follow-up analyses in a panel of BC cell lines of different molecular subtypes identified NOXA protein expression as a key determinant of paclitaxel sensitivity in triple-negative breast cancer (TNBC) cells. Moreover, we noted highest additive effects between paclitaxel and chemical inhibition of BCLX, but not BCL2 or MCL1, documenting dependence of TNBC cells on BCLX for survival and paclitaxel sensitivity defined by NOXA expression levels.