bluuebunny/crossref_metadata_2025_split huggingface dataset:
Receiver Function Mapping of the Mantle Transition Zone Beneath the Tian Shan Orogenic Belt
Authors: Liu Dongyang , Zhao Liang , Yuan Huaiyu , Sun Weijia , Xiao Wenjiao 
Published: November 2022

AbstractThis study provides new constraints on the mantle transition zone (MTZ) structure under the Tian Shan orogenic belt in the context of the double‐sided subduction of the Junggar lithosphere and the Tarim lithosphere. The 410‐ and 660‐km discontinuities bordering the MTZ under the Tian Shan and its adjacent areas are mapped by stacking 68,361 receiver functions from 4,122 events recorded by 100 broadband seismic stations. Regional and large‐scale 3‐D velocity models are used to explain the effect of the laterally heterogeneous velocity anomalies. We identify a thickened MTZ of about 9.3 km under the eastern Tian Shan and the Darbut belt. This thickening indicates a lower temperature, which is correlated with the broken‐off subducted lithosphere or the delamination of the eastern Tian Shan lithosphere. We document the thinning of the MTZ caused by the depressed 410‐km discontinuity and the uplifted 660‐km discontinuity across the Tian Shan orogenic belt, Junggar Basin and Tarim Basin. This thinning corresponds to a + 100 K thermal anomaly in the MTZ, and we suggest that it may have been produced by thermal upwelling originating from the lower mantle. The slightly thinned MTZ beneath the Altai Mountains was caused by the uplift of these two discontinuities, which is related to the high‐velocity anomalies in the upper mantle and MTZ. In contrast, the thinned MTZ below the easternmost segment of the Tian Shan orogenic belt, formed by the depression of 6.5 km for the 410‐km discontinuity may indicate the presence of small‐scale mantle upwelling.
Predicting Hydrological Drought With Bayesian Model Averaging Ensemble Vine Copula (BMAViC) Model
Authors: Wu Haijiang , Su Xiaoling , Singh Vijay P. , Zhang Te 
Published: November 2022

AbstractStreamflow deficit (hydrological drought) poses a large risk to water resources management, agricultural production, water supply, hydropower generation, and ecosystem services. Reliable and robust hydrological drought predictions are critical for water and food security and ecosystem health under anthropogenic warming. However, the prevalent statistical prediction methods, for example, the meta‐Gaussian (MG) model, usually do not lead to accurate drought predictions. We therefore developed a new drought prediction model utilizing the Bayesian Model Averaging coupled with Vine Copula, called Bayesian Model Averaging Ensemble Vine Copula (BMAViC) model, in which previous meteorological drought, antecedent evaporative drought, and preceding hydrological drought were selected as three predictors. The BMAViC model was applied to the Upper Yellow River basin and showed robust skills during calibration and validation periods for 1‐ to 3‐month lead hydrological drought predictions. In comparison with the MG model (reference model), the skills of the proposed model were relatively stable and superior under diverse lead times. Good performances under the 1‐ to 3‐month lead times strongly implied that the BMAViC model yielded robust and accurate hydrological drought predictions. The study results enhance our confidence in seasonal drought prediction and help us understand drought dynamics in future months.
Protein phosphatases regulate the liver microenvironment in the development of hepatocellular carcinoma
Authors: Yoon Joon-Sup , Lee Chang-Woo 
Published: November 2022

AbstractThe liver is a complicated heterogeneous organ composed of different cells. Parenchymal cells called hepatocytes and various nonparenchymal cells, including immune cells and stromal cells, are distributed in liver lobules with hepatic architecture. They interact with each other to compose the liver microenvironment and determine its characteristics. Although the liver microenvironment maintains liver homeostasis and function under healthy conditions, it also shows proinflammatory and profibrogenic characteristics that can induce the progression of hepatitis and hepatic fibrosis, eventually changing to a protumoral microenvironment that contributes to the development of hepatocellular carcinoma (HCC). According to recent studies, phosphatases are involved in liver diseases and HCC development by regulating protein phosphorylation in intracellular signaling pathways and changing the activities and characteristics of liver cells. Therefore, this review aims to highlight the importance of protein phosphatases in HCC development and in the regulation of the cellular components in the liver microenvironment and to show their significance as therapeutic targets.
Single-cell analysis of multiple myelomas refines the molecular features of bortezomib treatment responsiveness
Authors: Jung Seung-Hyun , Park Sung-Soo , Lim Ji-Young , Sohn Seon Yong , Kim Na Yung , Kim Dokyeong , Lee Sug Hyung , Chung Yeun-Jun , Min Chang-Ki 
Published: November 2022

AbstractBoth the tumor and tumor microenvironment (TME) are crucial for pathogenesis and chemotherapy resistance in multiple myeloma (MM). Bortezomib, commonly used for MM treatment, works on both MM and TME cells, but innate and acquired resistance easily develop. By single-cell RNA sequencing (scRNA-seq), we investigated bone marrow aspirates of 18 treatment-naïve MM patients who later received bortezomib-based treatments. Twelve plasma and TME cell types and their subsets were identified. Suboptimal responders (SORs) to bortezomib exhibited higher copy number alteration burdens than optimal responders (ORs). Forty-four differentially expressed genes for SORs based on scRNA-seq data were further analyzed in an independent cohort of 90 treatment-naïve MMs, where 24 genes were validated. A combined model of three clinical variables (older age, low absolute lymphocyte count, and no autologous stem cell transplantation) and 24 genes was associated with bortezomib responsiveness and poor prognosis. In T cells, cytotoxic memory, proliferating, and dysfunctional subsets were significantly enriched in SORs. Moreover, we identified three monocyte subsets associated with bortezomib responsiveness and an MM-specific NK cell trajectory that ended with an MM-specific subset. scRNA-seq predicted the interaction of the GAS6-MERTK, ALCAM-CD6, and BAG6-NCR gene networks. Of note, tumor cells from ORs and SORs were the most prominent sources of ALCAM on effector T cells and BAG6 on NK cells, respectively. Our results indicate that the complicated compositional and molecular changes of both tumor and immune cells in the bone marrow (BM) milieu are important in the development and acquisition of resistance to bortezomib-based treatment of MM.
Noncoding RNA PVT1 in osteosarcoma: The roles of lncRNA PVT1 and circPVT1
Authors: Wu Tingrui , Ji Ziyu , Lin Hao , Wei Bo , Xie Guohao , Ji Guangju , Fu Shijie , Huang Wenhua , Liu Huan 
Published: November 2022

AbstractOsteosarcoma (OS) is the most common primary malignant bone tumor in children and teenagers and is characterized by high malignant potential, rapid disease progression and high disability and mortality rates. Recently, noncoding RNAs (ncRNAs) have attracted the attention of many scholars due to their major regulatory roles in gene expression. Among them, lncRNA PVT1 and circPVT1 encoded by the PVT1 gene have been the focus of many studies; they are upregulated in OS, and abundant evidence indicates that lncRNA PVT1 and circPVT1 play key roles in the occurrence and development of OS. This review summarizes the mechanisms of action of lncRNA PVT1 and circPVT1 in regulating apoptosis, proliferation, glycolysis, invasion, migration and epithelial–mesenchymal transition (EMT) in OS and discusses their clinical applications in diagnosis, prognosis determination and drug resistance treatment, with the aim of helping researchers better understand the regulatory roles of lncRNA PVT1 and circPVT1 in OS progression and providing a theoretical basis for the development of early screening and accurate targeted treatment strategies and prognostic biomarkers for OS based on lncRNA PVT1 and circPVT1.
BH3 mimetics in combination with nilotinib or ponatinib represent a promising therapeutic strategy in blast phase chronic myeloid leukemia
Authors: Parry Narissa , Busch Caroline , Aßmann Victoria , Cassels Jennifer , Hair Alan , Helgason G. Vignir , Wheadon Helen , Copland Mhairi 
Published: November 2022

AbstractDysregulation of the BCL-2 family is implicated in protecting chronic myeloid leukemia (CML) cells from intracellular damage and BCR::ABL1-inhibition with tyrosine kinase inhibitors (TKIs) and may be a viable therapeutic target in blast phase (BP-)CML, for which treatment options are limited. BH3 mimetics, a class of small molecule inhibitors with high-specificity against the prosurvival members of the BCL-2 family, have displayed clinical promise in the treatment of chronic lymphocytic and acute myeloid leukemia as single agents and in combination with standard-of-care therapies. Here we present the first comparison of inhibition of BCL-2 prosurvival proteins BCL-2, BCL-xL and MCL-1 in combination with a second or third generation TKI, crucially with comparisons drawn between myeloid and lymphoid BP-CML samples. Co-treatment of four BP-CML cell lines with the TKIs nilotinib or ponatinib and either BCL-2 (venetoclax), MCL-1 (S63845) or BCL-xL (A-1331852) inhibitors resulted in a synergistic reduction in cell viability and increase in phosphatidylserine (PS) presentation. Nilotinib with BH3 mimetic combinations in myeloid BP-CML patient samples triggered increased induction of apoptosis over nilotinib alone, and a reduction in colony-forming capacity and CD34+ fraction, while this was not the case for lymphoid BP-CML samples tested. While some heterogeneity in apoptotic response was observed between cell lines and BP-CML patient samples, the combination of BCL-xL and BCR::ABL1 inhibition was consistently effective in inducing substantial apoptosis. Further, while BH3 mimetics showed little efficacy as single agents, dual-inhibition of BCL-2 prosurvival proteins dramatically induced apoptosis in all cell lines tested and in myeloid BP-CML patient samples compared to healthy donor samples. Gene expression and protein level analysis suggests a protective upregulation of alternative BCL-2 prosurvival proteins in response to BH3 mimetic single-treatment in BP-CML. Our results suggest that BH3 mimetics represent an interesting avenue for further exploration in myeloid BP-CML, for which alternative treatment options are desperately sought.
Single-cell sequencing unveils key contributions of immune cell populations in cancer-associated adipose wasting
Authors: Han Jun , Wang Yuchen , Qiu Yan , Sun Diya , Liu Yan , Li Zhigang , Zhou Ben , Zhang Haibing , Xiao Yichuan , Wu Guohao , Ding Qiurong 
Published: November 2022

AbstractAdipose tissue loss seen with cancer-associated cachexia (CAC) may functionally drive cachexia development. Using single-cell transcriptomics, we unveil a large-scale comprehensive cellular census of the stromal vascular fraction of white adipose tissues from patients with or without CAC. We report depot- and disease-specific clusters and developmental trajectories of adipose progenitors and immune cells. In adipose tissues with CAC, clear pro-inflammatory transitions were discovered in adipose progenitors, macrophages and CD8+ T cells, with dramatically remodeled cell interactome among these cells, implicating a synergistic effect in promoting tissue inflammation. Remarkably, activated CD8+ T cells contributed specifically to increased IFNG expression in adipose tissues from cachexia patients, and displayed a significant pro-catabolic effect on adipocytes in vitro; whereas macrophage depletion resulted in significantly rescued adipose catabolism and alleviated cachexia in a CAC animal model. Taken together, these results unveil causative mechanisms underlying the chronical inflammation and adipose wasting in CAC.
Indoor photovoltaic energy harvesting based on semiconducting π-conjugated polymers and oligomeric materials toward future IoT applications
Authors: Hwang Sunbin , Yasuda Takuma 
Published: November 2022

AbstractWith the advancement of artificial intelligence computing systems that can collect, analyze, and utilize metadata from our activities and surrounding environments, establishing self-powered electronic systems/networks supported by energy harvesters is strongly desired. With the lowering of power consumption in contemporary IoT electronics such as wireless sensors, indoor organic photovoltaic devices (iOPVs), which can be driven under ambient indoor light, have recently attracted significant interest as self-sustainable eco-friendly power sources. iOPVs based on organic semiconductors have unique advantages, such as light weight, flexibility, solution processability, and feasibility of low-temperature mass production. Additionally, the spectral tunability and high optical absorptivity of organic semiconductors make iOPVs more effective as energy harvesters in indoor lighting environments. With recent intensive research effort, iOPVs have realized the delivery of high power conversion efficiencies exceeding 25% with output power densities of several tens to a hundred μW cm−2, which are sufficient to drive various low-power electronics compatible with the IoT. This review article focuses on recent progress in iOPVs based on π-conjugated polymers and oligomeric materials and outlines their fundamental principles and characterization techniques.
High-affinity chromodomains engineered for improved detection of histone methylation and enhanced CRISPR-based gene repression
Authors: Veggiani G. , Villaseñor R. , Martyn G. D. , Tang J. Q. , Krone M. W. , Gu J. , Chen C. , Waters M. L. , Pearce K. H. , Baubec T. , Sidhu S. S. 
Published: November 2022

AbstractHistone methylation is an important post-translational modification that plays a crucial role in regulating cellular functions, and its dysregulation is implicated in cancer and developmental defects. Therefore, systematic characterization of histone methylation is necessary to elucidate complex biological processes, identify biomarkers, and ultimately, enable drug discovery. Studying histone methylation relies on the use of antibodies, but these suffer from lot-to-lot variation, are costly, and cannot be used in live cells. Chromatin-modification reader domains are potential affinity reagents for methylated histones, but their application is limited by their modest affinities. We used phage display to identify key residues that greatly enhance the affinities of Cbx chromodomains for methylated histone marks and develop a general strategy for enhancing the affinity of chromodomains of the human Cbx protein family. Our strategy allows us to develop powerful probes for genome-wide binding analysis and live-cell imaging. Furthermore, we use optimized chromodomains to develop extremely potent CRISPR-based repressors for tailored gene silencing. Our results highlight the power of engineered chromodomains for analyzing protein interaction networks involving chromatin and represent a modular platform for efficient gene silencing.
Brownian reservoir computing realized using geometrically confined skyrmion dynamics
Authors: Raab Klaus , Brems Maarten A. , Beneke Grischa , Dohi Takaaki , Rothörl Jan , Kammerbauer Fabian , Mentink Johan H. , Kläui Mathias 
Published: November 2022

AbstractReservoir computing (RC) has been considered as one of the key computational principles beyond von-Neumann computing. Magnetic skyrmions, topological particle-like spin textures in magnetic films are particularly promising for implementing RC, since they respond strongly nonlinearly to external stimuli and feature inherent multiscale dynamics. However, despite several theoretical proposals that exist for skyrmion reservoir computing, experimental realizations have been elusive until now. Here, we propose and experimentally demonstrate a conceptually new approach to skyrmion RC that leverages the thermally activated diffusive motion of skyrmions. By confining the electrically gated and thermal skyrmion motion, we find that already a single skyrmion in a confined geometry suffices to realize nonlinearly separable functions, which we demonstrate for the XOR gate along with all other Boolean logic gate operations. Besides this universality, the reservoir computing concept ensures low training costs and ultra-low power operation with current densities orders of magnitude smaller than those used in existing spintronic reservoir computing demonstrations. Our proposed concept is robust against device imperfections and can be readily extended by linking multiple confined geometries and/or by including more skyrmions in the reservoir, suggesting high potential for scalable and low-energy reservoir computing.
Prediction of inter-chain distance maps of protein complexes with 2D attention-based deep neural networks
Authors: Guo Zhiye , Liu Jian , Skolnick Jeffrey , Cheng Jianlin 
Published: November 2022

AbstractResidue-residue distance information is useful for predicting tertiary structures of protein monomers or quaternary structures of protein complexes. Many deep learning methods have been developed to predict intra-chain residue-residue distances of monomers accurately, but few methods can accurately predict inter-chain residue-residue distances of complexes. We develop a deep learning method CDPred (i.e., Complex Distance Prediction) based on the 2D attention-powered residual network to address the gap. Tested on two homodimer datasets, CDPred achieves the precision of 60.94% and 42.93% for top L/5 inter-chain contact predictions (L: length of the monomer in homodimer), respectively, substantially higher than DeepHomo’s 37.40% and 23.08% and GLINTER’s 48.09% and 36.74%. Tested on the two heterodimer datasets, the top Ls/5 inter-chain contact prediction precision (Ls: length of the shorter monomer in heterodimer) of CDPred is 47.59% and 22.87% respectively, surpassing GLINTER’s 23.24% and 13.49%. Moreover, the prediction of CDPred is complementary with that of AlphaFold2-multimer.
Effectiveness of a third BNT162b2 mRNA COVID-19 vaccination during pregnancy: a national observational study in Israel
Authors: Guedalia Joshua , Lipschuetz Michal , Calderon-Margalit Ronit , Cohen Sarah M. , Goldman-Wohl Debra , Kaminer Tali , Melul Eli , Shefer Galit , Sompolinsky Yishai , Walfisch Asnat , Yagel Simcha , Beharier Ofer 
Published: November 2022

AbstractThe Centers for Disease Control (CDC) recommend a third dose of COVID-19 vaccine for pregnant women, although data regarding effectiveness during pregnancy are lacking. This national, population-based, historical cohort study of pregnant women in Israel, delivering between August 1, 2021 and March 22, 2022, aims to analyze and compare the third and second doses’ vaccine effectiveness in preventing COVID-19-related hospitalizations during pregnancy during two COVID-19 waves (Delta variant in the summer of 2021 and Omicron, BA.1, variant in the winter of 2022). Time-dependent Cox proportional-hazards regression models estimate the hazard ratios (HR) and 95% confidence intervals (CI) for COVID-related outcomes according to vaccine dose, and vaccine effectiveness as 1-HR. Study includes 82,659 and 33,303 pregnant women from the Delta and Omicron waves, respectively. Compared with the second dose, the third dose effectively prevents overall hospitalizations with SARS-CoV-2 infections, with estimated effectiveness of 92% (95% CI 83–96%) during Delta, and enhances protection against significant disease during Omicron, with effectiveness of 92% (95% CI 26–99%), and 48% (95% CI 37–57%) effectiveness against hospitalization overall. A third dose of the BNT162b2 mRNA COVID-19 vaccine during pregnancy, given at least 5 months after the second vaccine dose, enhances protection against adverse COVID-19-related outcomes.
Muscle5: High-accuracy alignment ensembles enable unbiased assessments of sequence homology and phylogeny
Authors: Edgar Robert C. 
Published: November 2022

AbstractMultiple sequence alignments are widely used to infer evolutionary relationships, enabling inferences of structure, function, and phylogeny. Standard practice is to construct one alignment by some preferred method and use it in further analysis; however, undetected alignment bias can be problematic. I describe Muscle5, a novel algorithm which constructs an ensemble of high-accuracy alignment with diverse biases by perturbing a hidden Markov model and permuting its guide tree. Confidence in an inference is assessed as the fraction of the ensemble which supports it. Applied to phylogenetic tree estimation, I show that ensembles can confidently resolve topologies with low bootstrap according to standard methods, and conversely that some topologies with high bootstraps are incorrect. Applied to the phylogeny of RNA viruses, ensemble analysis shows that recently adopted taxonomic phyla are probably polyphyletic. Ensemble analysis can improve confidence assessment in any inference from an alignment.
Histone chaperone ASF1 mediates H3.3-H4 deposition in Arabidopsis
Authors: Zhong Zhenhui , Wang Yafei , Wang Ming , Yang Fan , Thomas Quentin Angelo , Xue Yan , Zhang Yaxin , Liu Wanlu , Jami-Alahmadi Yasaman , Xu Linhao , Feng Suhua , Marquardt Sebastian , Wohlschlegel James A. , Ausin Israel , Jacobsen Steven E. 
Published: November 2022

AbstractHistone chaperones and chromatin remodelers control nucleosome dynamics, which are essential for transcription, replication, and DNA repair. The histone chaperone Anti-Silencing Factor 1 (ASF1) plays a central role in facilitating CAF-1-mediated replication-dependent H3.1 deposition and HIRA-mediated replication-independent H3.3 deposition in yeast and metazoans. Whether ASF1 function is evolutionarily conserved in plants is unknown. Here, we show that Arabidopsis ASF1 proteins display a preference for the HIRA complex. Simultaneous mutation of both Arabidopsis ASF1 genes caused a decrease in chromatin density and ectopic H3.1 occupancy at loci typically enriched with H3.3. Genetic, transcriptomic, and proteomic data indicate that ASF1 proteins strongly prefers the HIRA complex over CAF-1. asf1 mutants also displayed an increase in spurious Pol II transcriptional initiation and showed defects in the maintenance of gene body CG DNA methylation and in the distribution of histone modifications. Furthermore, ectopic targeting of ASF1 caused excessive histone deposition, less accessible chromatin, and gene silencing. These findings reveal the importance of ASF1-mediated histone deposition for proper epigenetic regulation of the genome.