bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reconstruction of the Paleo‐Ocean Environment Using Mineralogical and Geochemical Analyses of Mixed‐Type Ferromanganese Nodules From the Tabletop of Western Pacific Magellan Seamount
Authors: Park Jinsub , Jung Jaewoo , Ko Youngtak , Lee Yongmoon , Yang Kiho 
Published: February 2023

AbstractVariations in the geochemistry and mineralogical compositions of ferromanganese (Fe‐Mn) nodules are closely related to variations in environmental parameters. Therefore, analysis of Fe‐Mn nodules can reconstruct the paleo‐ocean environment. Here, three differently shaped Fe‐Mn nodules were collected from the open seamount 9‐1 of the western Pacific Magellan Seamount. Geochemical and mineralogical analyses were conducted using micro X‐ray fluorescence (μ‐XRF) and Synchrotron X‐ray powder diffraction to reconstruct the paleo‐ocean environment. We found that the shape of the three nodules was different; however, the variations in their geochemical and mineralogical properties were similar. For all three nodules, the μ‐XRF elemental distribution revealed a distinct alternation between the Mn‐rich and Fe‐rich layers. The Mn‐rich and Fe‐rich layers surrounded the nuclei and appeared as concentric circles. Fe‐rich and Mn‐rich layers exhibited low Mn/Fe ratios (<2.5) and were dominated by vernadite, whereas layers with high Mn/Fe ratios (>2.5) were dominated by todorokite, respectively. These findings suggest an early diagenesis process at tabletop of the Magellan Seamount. The high contents of Ca and P and the existence of carbonate fluorapatite in the center of Fe‐Mn nodules indicate that the formation of these nodules began during the Miocene phosphatization event (19–16 Ma). In the early stages of nodule formation, a diagenetic process drove Fe‐Mn nodule formation. Because of global cooling from 9 Ma, early diagenesis was weakened, after which the formation of hydrogenetic Fe‐Mn nodules became dominant. As a result, variations in oxygen minimum zones and oxic‐suboxic fronts were recorded in Fe‐Mn nodules from tabletop of the seamount.
Elastic Interaction Between a Mesoscale Eddy‐Pair and an Axisymmetrical Eddy
Authors: Zoeller V. , Viúdez A. 
Published: February 2023

AbstractWe investigate numerically the elastic interaction between an eddy‐pair and an axisymmetrical eddy in inviscid isochoric two‐dimensional (2D) flows, as well as in three‐dimensional (3D) flows under the quasi‐geostrophic (QG) approximation. The eddy‐pair is a straight moving Lamb‐Chaplygin dipole where the absolute value of either its positive or negative amount of vorticity equals the vorticity of the axisymmetrical eddy. The results for the 2D and 3D cases show that interactions with almost no vorticity exchange, or vorticity loss to the background field between ocean eddies, but causing changes in their displacement velocity, are possible. When the eddy‐pair approaches the axisymmetrical eddy, their respective potential flows interact, the eddy‐pair's trajectory acquires curvature and their vorticity poles separate. In the QG dynamics, the eddies suffer little vertical deformation, being the barotropic effects dominant. At the moment of highest interaction, the anticyclonic eddy of the pair elongates, simultaneously the cyclonic eddy of the pair evolves toward spherical geometry, and the axisymmetrical eddy acquires prolate ellipsoidal geometry in the vertically stretched QG space. Once the eddy‐pair moves away from the axisymmetrical eddy, its poles close, returning to their original geometry, and the anticyclonic and cyclonic eddies continue as an eddy‐pair with a straight trajectory but along a new direction. The interaction is sensitive to the initial conditions and, depending on the initial position of the eddy‐pair, as well as on small changes in the vorticity distribution of the axisymmetrical eddy, inelastic interactions may instead occur.
Revisiting the Geographical Extent of Exceptional Warmth in the Early Paleogene Southern Ocean
Authors: Frieling J. , Bohaty S. M. , Cramwinckel Marlow J. , Gallagher S. J. , Holdgate G. R. , Reichgelt T. , Peterse F. , Pross J. , Sluijs A. , Bijl P. K. 
Published: February 2023

AbstractTo assess zonal temperature and biogeographical patterns in the Southern Ocean during the Paleogene, we present new multi‐proxy air‐ and sea‐surface temperature data for the latest Paleocene (∼57–56 Ma) and the Paleocene‐Eocene Thermal Maximum (PETM; ∼56 Ma) from the northern margin of the Australo‐Antarctic Gulf (AAG). The various proxy data sets document the well‐known late Paleocene warming and, superimposed, two transient late Paleocene pre‐cursor warming events, hundreds of kyr prior to the PETM. Remarkably, temperature reconstructions for the AAG and southwest Pacific during the latest Paleocene, PETM and Early Eocene Climatic Optimum (∼53–49 Ma) show similar trends as well as similar absolute temperatures east and west of the closed Tasmanian Gateway. Our data imply that the exceptional warmth as recorded by previous studies for the southwest Pacific extended westward into the AAG. This contrasts with modeling‐derived circulation and temperature patterns. We suggest that simulations of ocean circulation underestimate heat transport in the southwest Pacific due to insufficient resolution, not allowing for mesoscale eddy‐related heat transport. We argue for a systematic approach to tackle model and proxy biases that may occur in marginal marine settings and non‐analog high‐latitude climates to assess the temperature reconstructions.
Recent progress in three-terminal artificial synapses based on 2D materials: from mechanisms to applications
Authors: Zhang Fanqing , Li Chunyang , Li Zhongyi , Dong Lixin , Zhao Jing 
Published: February 2023

AbstractSynapses are essential for the transmission of neural signals. Synaptic plasticity allows for changes in synaptic strength, enabling the brain to learn from experience. With the rapid development of neuromorphic electronics, tremendous efforts have been devoted to designing and fabricating electronic devices that can mimic synapse operating modes. This growing interest in the field will provide unprecedented opportunities for new hardware architectures for artificial intelligence. In this review, we focus on research of three-terminal artificial synapses based on two-dimensional (2D) materials regulated by electrical, optical and mechanical stimulation. In addition, we systematically summarize artificial synapse applications in various sensory systems, including bioplastic bionics, logical transformation, associative learning, image recognition, and multimodal pattern recognition. Finally, the current challenges and future perspectives involving integration, power consumption and functionality are outlined.
Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies
Authors: Zhao Ailin , Zhou Hui , Yang Jinrong , Li Meng , Niu Ting 
Published: February 2023

AbstractHematologic malignancies are one of the most common cancers, and the incidence has been rising in recent decades. The clinical and molecular features of hematologic malignancies are highly heterogenous, and some hematologic malignancies are incurable, challenging the treatment, and prognosis of the patients. However, hematopoiesis and oncogenesis of hematologic malignancies are profoundly affected by epigenetic regulation. Studies have found that methylation-related mutations, abnormal methylation profiles of DNA, and abnormal histone deacetylase expression are recurrent in leukemia and lymphoma. Furthermore, the hypomethylating agents and histone deacetylase inhibitors are effective to treat acute myeloid leukemia and T-cell lymphomas, indicating that epigenetic regulation is indispensable to hematologic oncogenesis. Epigenetic regulation mainly includes DNA modifications, histone modifications, and noncoding RNA-mediated targeting, and regulates various DNA-based processes. This review presents the role of writers, readers, and erasers of DNA methylation and histone methylation, and acetylation in hematologic malignancies. In addition, this review provides the influence of microRNAs and long noncoding RNAs on hematologic malignancies. Furthermore, the implication of epigenetic regulation in targeted treatment is discussed. This review comprehensively presents the change and function of each epigenetic regulator in normal and oncogenic hematopoiesis and provides innovative epigenetic-targeted treatment in clinical practice.
Exploiting PRMT5 as a target for combination therapy in mantle cell lymphoma characterized by frequent ATM and TP53 mutations
Authors: Che Yuxuan , Liu Yang , Yao Yixin , Hill Holly A. , Li Yijing , Cai Qingsong , Yan Fangfang , Jain Preetesh , Wang Wei , Rui Lixin , Wang Michael 
Published: February 2023

AbstractConstant challenges for the treatment of mantle cell lymphoma (MCL) remain to be recurrent relapses and therapy resistance, especially in patients harboring somatic mutations in the tumor suppressors ATM and TP53, which are accumulated as therapy resistance emerges and the disease progresses, consistent with our OncoPrint results that ATM and TP53 alterations were most frequent in relapsed/refractory (R/R) MCL. We demonstrated that protein arginine methyltransferase-5 (PRMT5) was upregulated in R/R MCL, which predicted a poor prognosis. PRMT5 inhibitors displayed profound antitumor effects in the mouse models of MCL with mutated ATM and/or TP53, or refractory to CD19-targeted CAR T-cell therapy. Genetic knockout of PRMT5 robustly inhibited tumor growth in vivo. Co-targeting PRMT5, and ATR or CDK4 by using their inhibitors showed synergistic antitumor effects both in vitro and in vivo. Our results have provided a rational combination therapeutic strategy targeting multiple PRMT5-coordinated tumor-promoting processes for the treatment of R/R MCL with high mutation burdens.
VE-Cadherin modulates β-catenin/TCF-4 to enhance Vasculogenic Mimicry
Authors: Delgado-Bellido Daniel , Zamudio-Martínez Esteban , Fernández-Cortés Mónica , Herrera-Campos Ana Belén , Olmedo-Pelayo Joaquin , Perez Carmen Jordán , Expósito José , de Álava Enrique , Amaral Ana Teresa , Valle Francisco O’ , Diaz Angel Garcia , Oliver F. J. 
Published: February 2023

AbstractVasculogenic Mimicry (VM) refers to the capacity to form a blood network from aggressive cancer cells in an independent way of endothelial cells, to provide nutrients and oxygen leading to enhanced microenvironment complexity and treatment failure. In a previous study, we demonstrated that VE-Cadherin and its phosphorylation at Y658 modulated kaiso-dependent gene expression (CCND1 and Wnt 11) through a pathway involving Focal Adhesion kinase (FAK). In the present research, using a proteomic approach, we have found that β-catenin/TCF-4 is associated with nuclear VE-cadherin and enhances the capacity of malignant melanoma cells to undergo VM in cooperation with VE-Cadherin; in addition, preventing the phosphorylation of Y658 of VE-cadherin upon FAK disabling resulted in VE-Cadherin/β-catenin complex dissociation, increased β-catenin degradation while reducing TCF-4-dependent genes transcription (C-Myc and Twist-1). Uveal melanoma cells knockout for VE-Cadherin loses β-catenin expression while the rescue of VE-Cadherin (but not of the phosphorylation defective VE-Cadherin Y658F mutant) permits stabilization of β-catenin and tumor growth reduction in vivo experiments. In vivo, the concomitant treatment with the FAK inhibitor PF-271 and the anti-angiogenic agent bevacizumab leads to a strong reduction in tumor growth concerning the single treatment. In conclusion, the anomalous expression of VE-Cadherin in metastatic melanoma cells (from both uveal and cutaneous origins), together with its permanent phosphorylation at Y658, favors the induction of the aggressive VM phenotype through the cooperation of β-catenin with VE-Cadherin and by enhancing TCF-4 genes-dependent transcription.
PLK1 inhibition promotes apoptosis and DNA damage in glioma stem cells by regulating the nuclear translocation of YBX1
Authors: Li Xuetao , Chen Guangliang , Liu Bin , Tao Zhennan , Wu Yue , Zhang Kai , Feng Zibin , Huang Yulun , Wang Hao 
Published: February 2023

AbstractGlioma stem cells (GSCs) are the important cause of tumorigenesis, recurrence, and chemo(radio)resistance in glioma. Targeting GSCs helps improve the outcomes of glioma treatment. Polo-like kinase 1 (PLK1) is a member of the serine/threonine protein kinase family, which is highly conserved. In recent years, it has been suggested that increased levels of PLK1 and its activity are associated with tumor progression and poor prognosis. We aimed to identify whether PLK1 plays a critical role in stemness maintenance and apoptosis regulation in GSCs. Here we identify that PLK1 inhibition can induce apoptosis and DNA damage of GSCs, we have also delineat the possible underlying molecular mechanisms: PLK1 interacts with YBX1 and directly phosphorylates serine 174 and serine 176 of YBX1. Inhibition of PLK1 reduces the phosphorylation level of YBX1, and decreased phosphorylation of YBX1 prevents its nuclear translocation, thereby inducing apoptosis and DNA damage of GSCs. We confirmed that YBX1 knockdown resulted in the apoptosis and DNA damage of GSCs. These findings uncover that PLK1 inhibition induces cell apoptosis and DNA damage in GSCs through YBX1 phosphorylation, providing new insights into the mechanism by which PLK1 inhibition contributes to the apoptosis of and DNA damage in gliomas.
Separation of scales and a thermodynamic description of feature learning in some CNNs
Authors: Seroussi Inbar , Naveh Gadi , Ringel Zohar 
Published: February 2023

AbstractDeep neural networks (DNNs) are powerful tools for compressing and distilling information. Their scale and complexity, often involving billions of inter-dependent parameters, render direct microscopic analysis difficult. Under such circumstances, a common strategy is to identify slow variables that average the erratic behavior of the fast microscopic variables. Here, we identify a similar separation of scales occurring in fully trained finitely over-parameterized deep convolutional neural networks (CNNs) and fully connected networks (FCNs). Specifically, we show that DNN layers couple only through the second cumulant (kernels) of their activations and pre-activations. Moreover, the latter fluctuates in a nearly Gaussian manner. For infinite width DNNs, these kernels are inert, while for finite ones they adapt to the data and yield a tractable data-aware Gaussian Process. The resulting thermodynamic theory of deep learning yields accurate predictions in various settings. In addition, it provides new ways of analyzing and understanding DNNs in general.
Universal diamond edge Raman scale to 0.5 terapascal and implications for the metallization of hydrogen
Authors: Eremets M. I. , Minkov V. S. , Kong P. P. , Drozdov A. P. , Chariton S. , Prakapenka V. B. 
Published: February 2023

AbstractThe recent progress in generating static pressures up to terapascal values opens opportunities for studying novel materials with unusual properties, such as metallization of hydrogen and high-temperature superconductivity. However, an evaluation of pressure above ~0.3 terapascal is a challenge. We report a universal high-pressure scale up to ~0.5 terapascal, which is based on the shift of the Raman edge of stressed diamond anvils correlated with the equation of state of Au and does not require an additional pressure sensor. According to the new scale, the pressure values are substantially lower by 20% at ~0.5 terapascal compared to the extrapolation of the existing scales. We compare the available data of H2at the highest static pressures. We show that the onset of the proposed metallization of molecular hydrogen reported by different groups is consistent when corrected with the new scale and can be compared with various theoretical predictions.
Lipopolysaccharide biosynthesis and traffic in the envelope of the pathogen Brucella abortus
Authors: Servais Caroline , Vassen Victoria , Verhaeghe Audrey , Küster Nina , Carlier Elodie , Phégnon Léa , Mayard Aurélie , Auberger Nicolas , Vincent Stéphane , De Bolle Xavier 
Published: February 2023

AbstractLipopolysaccharide is essential for most Gram-negative bacteria as it is a main component of the outer membrane. In the pathogen Brucella abortus, smooth lipopolysaccharide containing the O-antigen is required for virulence. Being part of the Rhizobiales, Brucella spp. display unipolar growth and lipopolysaccharide was shown to be incorporated at the active growth sites, i.e. the new pole and the division site. By localizing proteins involved in the lipopolysaccharide transport across the cell envelope, from the inner to the outer membrane, we show that the lipopolysaccharide incorporation sites are determined by the inner membrane complex of the lipopolysaccharide transport system. Moreover, we identify the main O-antigen ligase of Brucella spp. involved in smooth lipopolysaccharide synthesis. Altogether, our data highlight a layer of spatiotemporal organization of the lipopolysaccharide biosynthesis pathway and identify an original class of bifunctional O-antigen ligases.
A versatile, high-efficiency platform for CRISPR-based gene activation
Authors: Heidersbach Amy J. , Dorighi Kristel M. , Gomez Javier A. , Jacobi Ashley M. , Haley Benjamin 
Published: February 2023

AbstractCRISPR-mediated transcriptional activation (CRISPRa) is a powerful technology for inducing gene expression from endogenous loci with exciting applications in high throughput gain-of-function genomic screens and the engineering of cell-based models. However, current strategies for generating potent, stable, CRISPRa-competent cell lines present limitations for the broad utility of this approach. Here, we provide a high-efficiency, self-selecting CRISPRa enrichment strategy, which combined with piggyBac transposon technology enables rapid production of CRISPRa-ready cell populations compatible with a variety of downstream assays. We complement this with an optimized guide RNA scaffold that significantly enhances CRISPRa functionality. Finally, we describe a synthetic guide RNA tool set that enables transient, population-wide gene activation when used with the self-selecting CRISPRa system. Taken together, this versatile platform greatly enhances the potential for CRISPRa across a wide variety of cellular contexts.
Watching the release of a photopharmacological drug from tubulin using time-resolved serial crystallography
Authors: Wranik Maximilian , Weinert Tobias , Slavov Chavdar , Masini Tiziana , Furrer Antonia , Gaillard Natacha , Gioia Dario , Ferrarotti Marco , James Daniel , Glover Hannah , Carrillo Melissa , Kekilli Demet , Stipp Robin , Skopintsev Petr , Brünle Steffen , Mühlethaler Tobias , Beale John , Gashi Dardan , Nass Karol , Ozerov Dmitry , Johnson Philip J. M. , Cirelli Claudio , Bacellar Camila , Braun Markus , Wang Meitian , Dworkowski Florian , Milne Chris , Cavalli Andrea , Wachtveitl Josef , Steinmetz Michel O. , Standfuss Jörg 
Published: February 2023

AbstractThe binding and release of ligands from their protein targets is central to fundamental biological processes as well as to drug discovery. Photopharmacology introduces chemical triggers that allow the changing of ligand affinities and thus biological activity by light. Insight into the molecular mechanisms of photopharmacology is largely missing because the relevant transitions during the light-triggered reaction cannot be resolved by conventional structural biology. Using time-resolved serial crystallography at a synchrotron and X-ray free-electron laser, we capture the release of the anti-cancer compound azo-combretastatin A4 and the resulting conformational changes in tubulin. Nine structural snapshots from 1 ns to 100 ms complemented by simulations show how cis-to-trans isomerization of the azobenzene bond leads to a switch in ligand affinity, opening of an exit channel, and collapse of the binding pocket upon ligand release. The resulting global backbone rearrangements are related to the action mechanism of microtubule-destabilizing drugs.
Mechanisms of the RNA helicases DDX42 and DDX46 in human U2 snRNP assembly
Authors: Yang Fenghua , Bian Tong , Zhan Xiechao , Chen Zhe , Xing Zhihan , Larsen Nicolas A. , Zhang Xiaofeng , Shi Yigong 
Published: February 2023

AbstractThree RNA helicases – DDX42, DDX46 and DHX15 – are found to be associated with human U2 snRNP, but their roles and mechanisms in U2 snRNP and spliceosome assembly are insufficiently understood. Here we report the cryo-electron microscopy (cryo-EM) structures of the DDX42-SF3b complex and a putative assembly precursor of 17S U2 snRNP that contains DDX42 (DDX42-U2 complex). DDX42 is anchored on SF3B1 through N-terminal sequences, with its N-plug occupying the RNA path of SF3B1. The binding mode of DDX42 to SF3B1 is in striking analogy to that of DDX46. In the DDX42-U2 complex, the N-terminus of DDX42 remains anchored on SF3B1, but the helicase domain has been displaced by U2 snRNA and TAT-SF1. Through in vitro assays, we show DDX42 and DDX46 are mutually exclusive in terms of binding to SF3b. Cancer-driving mutations of SF3B1 target the residues in the RNA path that directly interact with DDX42 and DDX46. These findings reveal the distinct roles of DDX42 and DDX46 in assembly of 17S U2 snRNP and provide insights into the mechanisms of SF3B1 cancer mutations.
Structure of a monomeric photosystem I core associated with iron-stress-induced-A proteins from Anabaena sp. PCC 7120
Authors: Nagao Ryo , Kato Koji , Hamaguchi Tasuku , Ueno Yoshifumi , Tsuboshita Naoki , Shimizu Shota , Furutani Miyu , Ehira Shigeki , Nakajima Yoshiki , Kawakami Keisuke , Suzuki Takehiro , Dohmae Naoshi , Akimoto Seiji , Yonekura Koji , Shen Jian-Ren 
Published: February 2023

AbstractIron-stress-induced-A proteins (IsiAs) are expressed in cyanobacteria under iron-deficient conditions. The cyanobacterium Anabaena sp. PCC 7120 has four isiA genes; however, their binding property and functional roles in PSI are still missing. We analyzed a cryo-electron microscopy structure of a PSI-IsiA supercomplex isolated from Anabaena grown under an iron-deficient condition. The PSI-IsiA structure contains six IsiA subunits associated with the PsaA side of a PSI core monomer. Three of the six IsiA subunits were identified as IsiA1 and IsiA2. The PSI-IsiA structure lacks a PsaL subunit; instead, a C-terminal domain of IsiA2 occupies the position of PsaL, which inhibits the oligomerization of PSI, leading to the formation of a PSI monomer. Furthermore, excitation-energy transfer from IsiAs to PSI appeared with a time constant of 55 ps. These findings provide insights into both the molecular assembly of the Anabaena IsiA family and the functional roles of IsiAs.
Widespread perturbation of ETS factor binding sites in cancer
Authors: Carrasco Pro Sebastian , Hook Heather , Bray David , Berenzy Daniel , Moyer Devlin , Yin Meimei , Labadorf Adam Thomas , Tewhey Ryan , Siggers Trevor , Fuxman Bass Juan Ignacio 
Published: February 2023

AbstractAlthough >90% of somatic mutations reside in non-coding regions, few have been reported as cancer drivers. To predict driver non-coding variants (NCVs), we present a transcription factor (TF)-aware burden test based on a model of coherent TF function in promoters. We apply this test to NCVs from the Pan-Cancer Analysis of Whole Genomes cohort and predict 2555 driver NCVs in the promoters of 813 genes across 20 cancer types. These genes are enriched in cancer-related gene ontologies, essential genes, and genes associated with cancer prognosis. We find that 765 candidate driver NCVs alter transcriptional activity, 510 lead to differential binding of TF-cofactor regulatory complexes, and that they primarily impact the binding of ETS factors. Finally, we show that different NCVs within a promoter often affect transcriptional activity through shared mechanisms. Our integrated computational and experimental approach shows that cancer NCVs are widespread and that ETS factors are commonly disrupted.