bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Thermo‐Compositional Model of the African Cratonic Lithosphere
Authors: Finger N.‐P. , Kaban M. K. , Tesauro M. , Mooney W. D. , Thomas M. 
Published: March 2022

AbstractRecently, the continually increasing availability of seismic data has allowed high‐resolution imaging of lithospheric structure beneath the African cratons. In this study, S‐wave seismic tomography is combined with high resolution satellite gravity data in an integrated approach to investigate the structure of the cratonic lithosphere of Africa. A new model for the Moho depth and data on the crustal density structure is employed along with global dynamic models to calculate residual topography and mantle gravity residuals. Corrections for thermal effects of an initially juvenile mantle are estimated based on S‐wave tomography and mineral physics. Joint inversion of the residuals yields necessary compositional adjustments that allow to recalculate the thermal effects. After several iterations, we obtain a consistent model of upper mantle temperature, thermal and compositional density variations, and Mg# as a measure of depletion, as well as an improved crustal density model. Our results show that thick and cold depleted lithosphere underlies West African, northern to central eastern Congo, and Zimbabwe Cratons. However, for most of these regions, the areal extent of their depleted lithosphere differs from the respective exposed Archean shields. Meanwhile, the lithosphere of Uganda, Tanzania, most of eastern and southern Congo, and the Kaapvaal Craton is thinner, warmer, and shows little or no depletion. Furthermore, the results allow to infer that the lithosphere of the exposed Archean shields of Congo and West African cratons was depleted before the single blocks were merged into their respective cratons.
The Deep‐Penetrating South Equatorial Undercurrent in the Tropical South Indian Ocean
Authors: Chen Gengxin , Han Weiqing , Zu Tingting , Chu Xiaoqing , Chen Ju 
Published: March 2022

AbstractA narrow eastward jet is detected beneath the westward‐flowing South Equatorial Current in the tropical South Indian Ocean (SIO) using in‐situ observation and reanalysis data. This jet is dubbed the South Equatorial Undercurrent (SEUC). The SEUC exists across the basin from about 60° to 105°E, with a core centered around 8°S in the west and shifted to approximately 10°S in the east and vertically extending from 200 m to more than 2,000 m. The SEUC is a seasonal feature that mainly occurs from January to June, and gradually weakens in July and August. The SEUC exhibits similar features as Tsuchiya jets in the Pacific and Atlantic Oceans, but also has its own uniqueness. This is the first time the SEUC is detected in the Indian Ocean, contributing to our understanding of the current system in the SIO, and basin‐scale and interbasin mass and property exchanges.
Corticosterone induces discrete epigenetic signatures in the dorsal and ventral hippocampus that depend upon sex and genotype: focus on methylated Nr3c1 gene
Authors: Caradonna Salvatore G. , Einhorn Nathan R. , Saudagar Vikram , Khalil Huzefa , Petty Gordon H. , Lihagen Axel , LeFloch Claire , Lee Francis S. , Akil Huda , Guidotti Alessandro , McEwen Bruce S. , Gatta Eleonora , Marrocco Jordan 
Published: March 2022

AbstractThe genomic effects of circulating glucocorticoids are particularly relevant in cortico-limbic structures, which express a high concentration of steroid hormone receptors. To date, no studies have investigated genomic differences in hippocampal subregions, namely the dorsal (dHPC) and ventral (vHPC) hippocampus, in preclinical models treated with exogenous glucocorticoids. Chronic oral corticosterone (CORT) in mouse is a pharmacological approach that disrupts the activity of the hypothalamic-pituitary-adrenal axis, increases affective behavior, and induces genomic changes after stress in the HPC of wildtype (WT) mice and mice heterozygous for the gene coding for brain-derived neurotrophic factor Val66Met (hMet), a variant associated with genetic susceptibility to stress. Using RNA-sequencing, we investigated the genomic signatures of oral CORT in the dHPC and vHPC of WT and hMet male and female mice, and examined sex and genotype differences in response to oral CORT. Males under CORT showed lower glycemia and increased anxiety- and depression-like behavior compared to females that showed instead opposite affective behavior in response to CORT. Rank–rank-hypergeometric overlap (RRHO) was used to identify genes from a continuous gradient of significancy that were concordant across groups. RRHO showed that CORT-induced differentially expressed genes (DEGs) in WT mice and hMet mice converged in the dHPC of males and females, while in the vHPC, DEGs converged in males and diverged in females. The vHPC showed a higher number of DEGs compared to the dHPC and exhibited sex differences related to glucocorticoid receptor (GR)-binding genes and epigenetic modifiers. Methyl-DNA-immunoprecipitation in the vHPC revealed differential methylation of the exons 1C and 1F of the GR gene (Nr3c1) in hMet females. Together, we report behavioral and endocrinological sex differences in response to CORT, as well as epigenetic signatures that i) differ in the dHPC and vHPC,ii) are distinct in males and females, and iii) implicate differential methylation of Nr3c1 selectively in hMet females.
TrkA-cholinergic signaling modulates fear encoding and extinction learning in PTSD-like behavior
Authors: Yanpallewar Sudhirkumar , Tomassoni-Ardori Francesco , Palko Mary Ellen , Hong Zhenyi , Kiris Erkan , Becker Jodi , Fulgenzi Gianluca , Tessarollo Lino 
Published: March 2022

AbstractRecent studies have suggested that the use of cognitive enhancers as adjuncts to exposure-based therapy in individuals suffering from post-traumatic stress disorder (PTSD) may be beneficial. Brain cholinergic signaling through basal forebrain projections to the hippocampus is an established pathway mediating fear response and cognitive flexibility. Here we employed a genetic strategy to enhance cholinergic activity through increased signaling of the NGF receptor TrkA. This strategy leads to increased levels of the marker of cholinergic activation, acetylcholine synthesizing enzyme choline acetyltransferase, in forebrain cholinergic regions and their projection areas such as the hippocampus. Mice with increased cholinergic activity do not display any neurobehavioral abnormalities except a selective attenuation of fear response and lower fear expression in extinction trials. Reduction in fear response is rescued by the GABA antagonist picrotoxin in mutant mice, and, in wild-type mice, is mimicked by the GABA agonist midazolam suggesting that GABA can modulate cholinergic functions on fear circuitries. Importantly, mutant mice also show a reduction in fear processing under stress conditions in a single prolonged stress (SPS) model of PTSD-like behavior, and augmentation of cholinergic signaling by the drug donepezil in wild-type mice promotes extinction learning in a similar SPS model of PTSD-like behavior. Donepezil is already in clinical use for the treatment of dementia suggesting a new translational application of this drug for improving exposure-based psychotherapy in PTSD patients.
Cytogenetic abnormalities in essential thrombocythemia: Clinical and molecular correlates and prognostic relevance in 809 informative cases
Authors: Gangat Naseema , Jadoon Yamna , Szuber Natasha , Hanson Curtis A. , Wolanskyj-Spinner Alexandra P. , Ketterling Rhett P. , Pardanani Animesh , Tefferi Ayalew 
Published: March 2022

AbstractCytogenetic studies among 809 consecutive patients with essential thrombocythemia (ET; median age 59 years; 65% females) revealed normal karyotype in 754 (93%), loss of chromosome Y only (-Y) in 16 (2%), and abnormalities other than -Y in 39 (4.8%), the most frequent being sole 20q- (n = 8). At presentation, abnormal karyotype, excluding -Y, was associated with older age (p = 0.04), higher leukocyte count (p = 0.03) and arterial thrombosis history (p = 0.02); no associations were apparent for JAK2/CALR/MPL mutations whereas ASXL1 mutations clustered with normal karyotype/-Y and TP53 with abnormal karyotype. Survival was significantly shorter in patients with abnormal karyotype or -Y, compared to those with normal karyotype (median 12, 10, and 21 years, respectively; p < 0.0001). During multivariable analysis that included IPSET (international prognostic score for ET) variables, abnormal karyotype (p < 0.01, HR 2.0), age >60 years (p < 0.01, HR 4.5), leukocytosis >11 × 109/L (p < 0.01, HR 1.5), and male gender (p < 0.01, HR 1.4) were independently associated with inferior survival; abnormal karyotype and age >60 years remained significant, along with SF3B1/SRSF2/U2AF1/TP53 mutations (p = 0.04; HR 2.9), when the latter was included in the multivariable model. The current study suggests prognostic relevance for karyotype in ET.
GNE-493 inhibits prostate cancer cell growth via Akt-mTOR-dependent and -independent mechanisms
Authors: Jin Lu , Zhang Wei , Yao Ming-Yu , Tian Ye , Xue Bo-xin , Tao Wei 
Published: March 2022

AbstractGNE-493 is a novel PI3K/mTOR dual inhibitor with improved metabolic stability, oral bioavailability, and excellent pharmacokinetic parameters. Here GNE-493 potently inhibited viability, proliferation, and migration in different primary and established (LNCaP and PC-3 lines) prostate cancer cells, and provoking apoptosis. GNE-493 blocked Akt-mTOR activation in primary human prostate cancer cells. A constitutively-active mutant Akt1 restored Akt-mTOR activation but only partially ameliorated GNE-493-induced prostate cancer cell death. Moreover, GNE-493 was still cytotoxic in Akt1/2-silenced primary prostate cancer cells. Significant oxidative stress and programmed necrosis cascade activation were detected in GNE-493-treated prostate cancer cells. Moreover, GNE-493 downregulated Sphingosine Kinase 1 (SphK1), causing ceramide accumulation in primary prostate cancer cells. Daily single dose GNE-493 oral administration robustly inhibited the growth of the prostate cancer xenograft in the nude mice. Akt-mTOR inactivation, SphK1 downregulation, ceramide level increase, and oxidative injury were detected in GNE-493-treated prostate cancer xenograft tissues. Together, GNE-493 inhibited prostate cancer cell growth possibly through the Akt-mTOR-dependent and -independent mechanisms.
Multi-omic cross-sectional cohort study of pre-malignant Barrett’s esophagus reveals early structural variation and retrotransposon activity
Authors: Katz-Summercorn A. C. , Jammula S. , Frangou A. , Peneva I. , O’Donovan M. , Tripathi M. , Malhotra S. , di Pietro M. , Abbas S. , Devonshire G. , Januszewicz W. , Blasko A. , Nowicki-Osuch K. , MacRae S. , Northrop A. , Redmond A. M. , Wedge D. C. , Fitzgerald R. C. 
Published: March 2022

AbstractBarrett’s esophagus is a pre-malignant lesion that can progress to esophageal adenocarcinoma. We perform a multi-omic analysis of pre-cancer samples from 146 patients with a range of outcomes, comprising 642 person years of follow-up. Whole genome sequencing reveals complex structural variants and LINE-1 retrotransposons, as well as known copy number changes, occurring even prior to dysplasia. The structural variant burden captures the most variance across the cohort and genomic profiles do not always match consensus clinical pathology dysplasia grades. Increasing structural variant burden is associated with: high levels of chromothripsis and breakage-fusion-bridge events; increased expression of genes related to cell cycle checkpoint, DNA repair and chromosomal instability; and epigenetic silencing of Wnt signalling and cell cycle genes. Timing analysis reveals molecular events triggering genomic instability with more clonal expansion in dysplastic samples. Overall genomic complexity occurs early in the Barrett’s natural history and may inform the potential for cancer beyond the clinically discernible phenotype.
Human rhinovirus promotes STING trafficking to replication organelles to promote viral replication
Authors: Triantafilou Martha , Ramanjulu Joshi , Booty Lee M. , Jimenez-Duran Gisela , Keles Hakan , Saunders Ken , Nevins Neysa , Koppe Emma , Modis Louise K. , Pesiridis G. Scott , Bertin John , Triantafilou Kathy 
Published: March 2022

AbstractHuman rhinovirus (HRV), like coronavirus (HCoV), are positive-strand RNA viruses that cause both upper and lower respiratory tract illness, with their replication facilitated by concentrating RNA-synthesizing machinery in intracellular compartments made of modified host membranes, referred to as replication organelles (ROs). Here we report a non-canonical, essential function for stimulator of interferon genes (STING) during HRV infections. While the canonical function of STING is to detect cytosolic DNA and activate inflammatory responses, HRV infection triggers the release of STIM1-bound STING in the ER by lowering Ca2+, thereby allowing STING to interact with phosphatidylinositol 4-phosphate (PI4P) and traffic to ROs to facilitates viral replication and transmission via autophagy. Our results thus hint a critical function of STING in HRV viral replication and transmission, with possible implications for other RO-mediated RNA viruses.
Real-space nanoimaging of THz polaritons in the topological insulator Bi2Se3
Authors: Chen Shu , Bylinkin Andrei , Wang Zhengtianye , Schnell Martin , Chandan Greeshma , Li Peining , Nikitin Alexey Y. , Law Stephanie , Hillenbrand Rainer 
Published: March 2022

AbstractPlasmon polaritons in topological insulators attract attention from a fundamental perspective and for potential THz photonic applications. Although polaritons have been observed by THz far-field spectroscopy on topological insulator microstructures, real-space imaging of propagating THz polaritons has been elusive so far. Here, we show spectroscopic THz near-field images of thin Bi2Se3 layers (prototypical topological insulators) revealing polaritons with up to 12 times increased momenta as compared to photons of the same energy and decay times of about 0.48 ps, yet short propagation lengths. From the images we determine and analyze the polariton dispersion, showing that the polaritons can be explained by the coupling of THz radiation to various combinations of Dirac and massive carriers at the Bi2Se3 surfaces, massive bulk carriers and optical phonons. Our work provides critical insights into the nature of THz polaritons in topological insulators and establishes instrumentation and methodology for imaging of THz polaritons.
Medial prefrontal cortex and anteromedial thalamus interaction regulates goal-directed behavior and dopaminergic neuron activity
Authors: Yang Chen , Hu Yuzheng , Talishinsky Aleksandr D. , Potter Christian T. , Calva Coleman B. , Ramsey Leslie A. , Kesner Andrew J. , Don Reuben F. , Junn Sue , Tan Aaron , Pierce Anne F. , Nicolas Céline , Arima Yosuke , Lee Seung-Chan , Su Conghui , Coudriet Jensine M. , Mejia-Aponte Carlos A. , Wang Dong V. , Lu Hanbing , Yang Yihong , Ikemoto Satoshi 
Published: March 2022

AbstractThe prefrontal cortex is involved in goal-directed behavior. Here, we investigate circuits of the PFC regulating motivation, reinforcement, and its relationship to dopamine neuron activity. Stimulation of medial PFC (mPFC) neurons in mice activated many downstream regions, as shown by fMRI. Axonal terminal stimulation of mPFC neurons in downstream regions, including the anteromedial thalamic nucleus (AM), reinforced behavior and activated midbrain dopaminergic neurons. The stimulation of AM neurons projecting to the mPFC also reinforced behavior and activated dopamine neurons, and mPFC and AM showed a positive-feedback loop organization. We also found using fMRI in human participants watching reinforcing video clips that there is reciprocal excitatory functional connectivity, as well as co-activation of the two regions. Our results suggest that this cortico-thalamic loop regulates motivation, reinforcement, and dopaminergic neuron activity.
Chemistry-mediated Ostwald ripening in carbon-rich C/O systems at extreme conditions
Authors: Lindsey Rebecca K. , Goldman Nir , Fried Laurence E. , Bastea Sorin 
Published: March 2022

AbstractThere is significant interest in establishing a capability for tailored synthesis of next-generation carbon-based nanomaterials due to their broad range of applications and high degree of tunability. High pressure (e.g., shockwave-driven) synthesis holds promise as an effective discovery method, but experimental challenges preclude elucidating the processes governing nanocarbon production from carbon-rich precursors that could otherwise guide efforts through the prohibitively expansive design space. Here we report findings from large scale atomistically-resolved simulations of carbon condensation from C/O mixtures subjected to extreme pressures and temperatures, made possible by machine-learned reactive interatomic potentials. We find that liquid nanocarbon formation follows classical growth kinetics driven by Ostwald ripening (i.e., growth of large clusters at the expense of shrinking small ones) and obeys dynamical scaling in a process mediated by carbon chemistry in the surrounding reactive fluid. The results provide direct insight into carbon condensation in a representative system and pave the way for its exploration in higher complexity organic materials. They also suggest that simulations using machine-learned interatomic potentials could eventually be employed as in-silico design tools for new nanomaterials.
Structural basis for activation and gating of IP3 receptors
Authors: Schmitz Emily A. , Takahashi Hirohide , Karakas Erkan 
Published: March 2022

AbstractA pivotal component of the calcium (Ca2+) signaling toolbox in cells is the inositol 1,4,5-triphosphate (IP3) receptor (IP3R), which mediates Ca2+ release from the endoplasmic reticulum (ER), controlling cytoplasmic and organellar Ca2+ concentrations. IP3Rs are co-activated by IP3 and Ca2+, inhibited by Ca2+ at high concentrations, and potentiated by ATP. However, the underlying molecular mechanisms are unclear. Here we report cryo-electron microscopy (cryo-EM) structures of human type-3 IP3R obtained from a single dataset in multiple gating conformations: IP3-ATP bound pre-active states with closed channels, IP3-ATP-Ca2+ bound active state with an open channel, and IP3-ATP-Ca2+ bound inactive state with a closed channel. The structures demonstrate how IP3-induced conformational changes prime the receptor for activation by Ca2+, how Ca2+ binding leads to channel opening, and how ATP modulates the activity, providing insights into the long-sought questions regarding the molecular mechanism underpinning receptor activation and gating.
Decoding lip language using triboelectric sensors with deep learning
Authors: Lu Yijia , Tian Han , Cheng Jia , Zhu Fei , Liu Bin , Wei Shanshan , Ji Linhong , Wang Zhong Lin 
Published: March 2022

AbstractLip language is an effective method of voice-off communication in daily life for people with vocal cord lesions and laryngeal and lingual injuries without occupying the hands. Collection and interpretation of lip language is challenging. Here, we propose the concept of a novel lip-language decoding system with self-powered, low-cost, contact and flexible triboelectric sensors and a well-trained dilated recurrent neural network model based on prototype learning. The structural principle and electrical properties of the flexible sensors are measured and analysed. Lip motions for selected vowels, words, phrases, silent speech and voice speech are collected and compared. The prototype learning model reaches a test accuracy of 94.5% in training 20 classes with 100 samples each. The applications, such as identity recognition to unlock a gate, directional control of a toy car and lip-motion to speech conversion, work well and demonstrate great feasibility and potential. Our work presents a promising way to help people lacking a voice live a convenient life with barrier-free communication and boost their happiness, enriches the diversity of lip-language translation systems and will have potential value in many applications.
Growing single crystals of two-dimensional covalent organic frameworks enabled by intermediate tracing study
Authors: Kang Chengjun , Yang Kuiwei , Zhang Zhaoqiang , Usadi Adam K. , Calabro David C. , Baugh Lisa Saunders , Wang Yuxiang , Jiang Jianwen , Zou Xiaodong , Huang Zhehao , Zhao Dan 
Published: March 2022

AbstractResolving single-crystal structures of two-dimensional covalent organic frameworks (2D COFs) is a great challenge, hindered in part by limited strategies for growing high-quality crystals. A better understanding of the growth mechanism facilitates development of methods to grow high-quality 2D COF single crystals. Here, we take a different perspective to explore the 2D COF growth process by tracing growth intermediates. We discover two different growth mechanisms, nucleation and self-healing, in which self-assembly and pre-arrangement of monomers and oligomers are important factors for obtaining highly crystalline 2D COFs. These findings enable us to grow micron-sized 2D single crystalline COF Py-1P. The crystal structure of Py-1P is successfully characterized by three-dimensional electron diffraction (3DED), which confirms that Py-1P does, in part, adopt the widely predicted AA stacking structure. In addition, we find the majority of Py-1P crystals (>90%) have a previously unknown structure, containing 6 stacking layers within one unit cell.
Strain-level characterization of broad host range mobile genetic elements transferring antibiotic resistance from the human microbiome
Authors: Forster Samuel C. , Liu Junyan , Kumar Nitin , Gulliver Emily L. , Gould Jodee A. , Escobar-Zepeda Alejandra , Mkandawire Tapoka , Pike Lindsay J. , Shao Yan , Stares Mark D. , Browne Hilary P. , Neville B. Anne , Lawley Trevor D. 
Published: March 2022

AbstractMobile genetic elements (MGEs) carrying antibiotic resistance genes (ARGs) disseminate ARGs when they mobilise into new bacterial hosts. The nature of such horizontal gene transfer (HGT) events between human gut commensals and pathogens remain poorly characterised. Here, we compare 1354 cultured commensal strains (540 species) to 45,403 pathogen strains (12 species) and find 64,188 MGE-mediated ARG transfer events between the two groups using established methods. Among the 5931 MGEs, we find 15 broad host range elements predicted to have crossed different bacterial phyla while also occurring in animal and environmental microbiomes. We experimentally demonstrate that predicted broad host range MGEs can mobilise from commensals Dorea longicatena and Hungatella hathewayi to pathogen Klebsiella oxytoca, crossing phyla simultaneously. Our work establishes the MGE-mediated ARG dissemination network between human gut commensals and pathogens and highlights broad host range MGEs as targets for future ARG dissemination management.