bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Vine Copula‐Based Polynomial Chaos Framework for Improving Multi‐Model Hydroclimatic Projections at a Multi‐Decadal Convection‐Permitting Scale
Authors: Zhang Boen , Wang Shuo , Qing Yamin , Zhu Jinxin , Wang Dagang , Liu Jiafeng 
Published: May 2022

AbstractPhysically based hydrologic models have been extensively used for hydroclimatic projections, but key challenges remain owing to the heavy computational burden and structural variability of physically based models. In this study, we develop a vine copula‐based polynomial chaos framework for improving multi‐model projections of hydroclimatic regimes at a convection‐permitting scale over the Dongjiang River Basin located in South China. Specifically, a deep neural network (DNN)‐based polynomial chaos expansion (PCE) is developed to significantly improve the efficiency of probabilistic hydrologic predictions. A vine copula multi‐model ensemble approach is also proposed to robustly combine hydrologic predictions generated from multiple DNN‐based PCEs to improve reliability and accuracy. To assess regional hydrologic responses to changing climate, multi‐decadal nested‐grid climate projections over the Guangdong‐Hong Kong‐Macao Greater Bay Area (GBA) are developed using the convection‐permitting Weather Research and Forecasting (WRF) model with 4‐km horizontal grid spacing. Our findings reveal that the DNN‐based PCEs achieve comparable performance to the physically based hydrologic predictions with an extremely low computational cost. The vine copula multi‐model ensemble approach outperforms the Bayesian model averaging (BMA) by generating more accurate and reliable hydrologic predictions. The developed framework and physical models also lead to consistent projections of future changes in streamflow regimes. Our findings reveal that the projected increases in the frequency and intensity of extreme precipitation can lead to substantial increases in flood magnitudes, but the increases may not be obvious for river basins affected by multiple reservoirs.
WNT5A promotes the metastasis of esophageal squamous cell carcinoma by activating the HDAC7/SNAIL signaling pathway
Authors: Feng Yingtong , Ma Zhiqiang , Pan Minghong , Xu Liqun , Feng Junjun , Zhang Yimeng , Shao Changjian , Guo Kai , Duan Hongtao , Zhang Yujing , Zhang Yuxi , Zhang Jiao , Lu Di , Ren Xiaoya , Han Jing , Li Xiaofei , Yan Xiaolong 
Published: May 2022

AbstractEsophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide, with high incidence and mortality rates and low survival rates. However, the detailed molecular mechanism of ESCC progression remains unclear. Here, we first showed significantly higher WNT5A and SNAIL expression in ESCC samples than in corresponding paracancerous samples. High WNT5A and SNAIL expression levels correlated positively with lymphatic metastasis and poor prognosis for patients with ESCC based on immunohistochemical (IHC) staining of 145 paired ESCC samples. Spearman’s correlation analyses confirmed the strong positive correlation between WNT5A and SNAIL expression, and patients with ESCC presenting coexpression of WNT5A and SNAIL had the worst prognosis. Then, we verified that the upregulation of WNT5A promoted ESCC cell metastasis in vivo and in vitro, suggesting that WNT5A might be a promising therapeutic target for the prevention of ESCC. Furthermore, WNT5A overexpression induced the epithelial-mesenchymal transition via histone deacetylase 7 (HDAC7) upregulation, and HDAC7 silencing significantly reversed WNT5A-induced SNAIL upregulation and ESCC cell metastasis. In addition, we used HDAC7 inhibitors (SAHA and TMP269) to further confirm that HDAC7 participates in WNT5A-mediated carcinogenesis. Based on these results, HDAC7 is involved in WNT5A-mediated ESCC progression, and approaches targeting WNT5A and HDAC7 might be potential therapeutic strategies for ESCC.
Cancer associated fibroblast–derived CCL5 promotes hepatocellular carcinoma metastasis through activating HIF1α/ZEB1 axis
Authors: Xu Haixu , Zhao Jie , Li Jinping , Zhu Zhifeng , Cui Zhaohai , Liu Ran , Lu Rong , Yao Zhi , Xu Qiong 
Published: May 2022

AbstractCancer-associated fibroblasts (CAFs) are one of the most enriched components of Hepatocellular carcinoma (HCC) microenvironment, which are tightly related to the metastasis and invasion of HCC. We identified a mechanism by which CAF-derived chemokine CCL5 enhanced HCC metastasis by triggering the HIF1α/ZEB1 axis. We demonstrated that CAFs derived from HCC tissues promoted the migration and invasion of HCC cells and facilitated metastasis to the lung of NOD/SCID mice. Then the chemokine antibody array elucidated the higher chemokine CCL5 level secreted by CAFs than by paracancerous tissue fibroblasts (PTFs). Mechanistically, we found that CAF-derived CCL5 inhibited the ubiquitination and degradation of hypoxia-inducible factor 1 alpha (HIF1α) by binding to specific receptors, maintained HIF1α under normoxia, thereby up-regulated the downstream gene zinc finger enhancer-binding protein 1 (ZEB1) and induced epithelial-mesenchymal transition (EMT), ultimately validating its ability to promote lung metastasis of HCC. And this novel mechanism may have association with poor prognosis. Taken together, targeting CAF-derived CCL5 mediated HIF1α/ZEB1 cascade possibly propose a new therapeutic route for HCC.
A 3D gene expression atlas of the floral meristem based on spatial reconstruction of single nucleus RNA sequencing data
Authors: Neumann Manuel , Xu Xiaocai , Smaczniak Cezary , Schumacher Julia , Yan Wenhao , Blüthgen Nils , Greb Thomas , Jönsson Henrik , Traas Jan , Kaufmann Kerstin , Muino Jose M. 
Published: May 2022

AbstractCellular heterogeneity in growth and differentiation results in organ patterning. Single-cell transcriptomics allows characterization of gene expression heterogeneity in developing organs at unprecedented resolution. However, the original physical location of the cell is lost during this methodology. To recover the original location of cells in the developing organ is essential to link gene activity with cellular identity and function in plants. Here, we propose a method to reconstruct genome-wide gene expression patterns of individual cells in a 3D flower meristem by combining single-nuclei RNA-seq with microcopy-based 3D spatial reconstruction. By this, gene expression differences among meristematic domains giving rise to different tissue and organ types can be determined. As a proof of principle, the method is used to trace the initiation of vascular identity within the floral meristem. Our work demonstrates the power of spatially reconstructed single cell transcriptome atlases to understand plant morphogenesis. The floral meristem 3D gene expression atlas can be accessed at http://threed-flower-meristem.herokuapp.com.
Inhibition of the CDK2 and Cyclin A complex leads to autophagic degradation of CDK2 in cancer cells
Authors: Zhang Jiawei , Gan Yichao , Li Hongzhi , Yin Jie , He Xin , Lin Liming , Xu Senlin , Fang Zhipeng , Kim Byung-wook , Gao Lina , Ding Lili , Zhang Eryun , Ma Xiaoxiao , Li Junfeng , Li Ling , Xu Yang , Horne David , Xu Rongzhen , Yu Hua , Gu Ying , Huang Wendong 
Published: May 2022

AbstractCyclin-dependent kinase 2 (CDK2) complex is significantly over-activated in many cancers. While it makes CDK2 an attractive target for cancer therapy, most inhibitors against CDK2 are ATP competitors that are either nonspecific or highly toxic, and typically fail clinical trials. One alternative approach is to develop non-ATP competitive inhibitors; they disrupt interactions between CDK2 and either its partners or substrates, resulting in specific inhibition of CDK2 activities. In this report, we identify two potential druggable pockets located in the protein-protein interaction interface (PPI) between CDK2 and Cyclin A. To target the potential druggable pockets, we perform a LIVS in silico screening of a library containing 1925 FDA approved drugs. Using this approach, homoharringtonine (HHT) shows high affinity to the PPI and strongly disrupts the interaction between CDK2 and cyclins. Further, we demonstrate that HHT induces autophagic degradation of the CDK2 protein via tripartite motif 21 (Trim21) in cancer cells, which is confirmed in a leukemia mouse model and in human primary leukemia cells. These results thus identify an autophagic degradation mechanism of CDK2 protein and provide a potential avenue towards treating CDK2-dependent cancers.
Automated next-generation profiling of genomic alterations in human cancers
Authors: Keefer Laurel A. , White James R. , Wood Derrick E. , Gerding Kelly M. R. , Valkenburg Kenneth C. , Riley David , Gault Christopher , Papp Eniko , Vollmer Christine M. , Greer Amy , Hernandez James , McGregor Paul M. , Zingone Adriana , Ryan Bríd M. , Deak Kristen , McCall Shannon J. , Datto Michael B. , Prescott James L. , Thompson John F. , Cerqueira Gustavo C. , Jones Siân , Simmons John K. , McElhinny Abigail , Dickey Jennifer , Angiuoli Samuel V. , Diaz Luis A. , Velculescu Victor E. , Sausen Mark 
Published: May 2022

AbstractThe lack of validated, distributed comprehensive genomic profiling assays for patients with cancer inhibits access to precision oncology treatment. To address this, we describe elio tissue complete, which has been FDA-cleared for examination of 505 cancer-related genes. Independent analyses of clinically and biologically relevant sequence changes across 170 clinical tumor samples using MSK-IMPACT, FoundationOne, and PCR-based methods reveals a positive percent agreement of >97%. We observe high concordance with whole-exome sequencing for evaluation of tumor mutational burden for 307 solid tumors (Pearson r = 0.95) and comparison of the elio tissue complete microsatellite instability detection approach with an independent PCR assay for 223 samples displays a positive percent agreement of 99%. Finally, evaluation of amplifications and translocations against DNA- and RNA-based approaches exhibits >98% negative percent agreement and positive percent agreement of 86% and 82%, respectively. These methods provide an approach for pan-solid tumor comprehensive genomic profiling with high analytical performance.
Memory, switches, and an OR-port through bistability in chemically fueled crystals
Authors: Schnitter Fabian , Rieß Benedikt , Jandl Christian , Boekhoven Job 
Published: May 2022

AbstractThe ability to store information in chemical reaction networks is essential for the complex behavior we associate with life. In biology, cellular memory is regulated through transcriptional states that are bistable, i.e., a state that can either be on or off and can be flipped from one to another through a transient signal. Such memory circuits have been realized synthetically through the rewiring of genetic systems in vivo or through the rational design of reaction networks based on DNA and highly evolved enzymes in vitro. Completely bottom-up analogs based on small molecules are rare and hard to design and thus represent a challenge for systems chemistry. In this work, we show that bistability can be designed from a simple non-equilibrium reaction cycle that is coupled to crystallization. The crystals exert the necessary feedback on the reaction cycle required for the bistability resulting in an on-state with assemblies and an off-state without. Each state represents volatile memory that can be stored in continuously stirred tank reactors indefinitely even though molecules are turned over on a minute-timescale. We showcase the system’s abilities by creating a matrix display that can store images and by creating an OR-gate by coupling several switches together.
Dynamic character displacement among a pair of bacterial phyllosphere commensals in situ
Authors: Hemmerle Lucas , Maier Benjamin A. , Bortfeld-Miller Miriam , Ryback Birgitta , Gäbelein Christoph G. , Ackermann Martin , Vorholt Julia A. 
Published: May 2022

AbstractDifferences between species promote stable coexistence in a resource-limited environment. These differences can result from interspecies competition leading to character shifts, a process referred to as character displacement. While character displacement is often interpreted as a consequence of genetically fixed trait differences between species, it can also be mediated by phenotypic plasticity in response to the presence of another species. Here, we test whether phenotypic plasticity leads to a shift in proteome allocation during co-occurrence of two bacterial species from the abundant, leaf-colonizing familiesSphingomonadaceaeandRhizobiaceaein their natural habitat. Upon mono-colonizing of the phyllosphere, both species exhibit specific and shared protein functions indicating a niche overlap. During co-colonization, quantitative differences in the protein repertoire of both bacterial populations occur as a result of bacterial coexistencein planta. Specifically, theSphingomonasstrain produces enzymes for the metabolization of xylan, while theRhizobiumstrain reprograms its metabolism to beta-oxidation of fatty acids fueled via the glyoxylate cycle and adapts its biotin acquisition. We demonstrate the conditional relevance of cross-species facilitation by mutagenesis leading to loss of fitness in competitionin planta. Our results show that dynamic character displacement and niche facilitation mediated by phenotypic plasticity can contribute to species coexistence.
Metabolic control of progenitor cell propagation during Drosophila tracheal remodeling
Authors: Li Yue , Dong Pengzhen , Yang Yang , Guo Tianyu , Zhao Quanyi , Miao Dan , Li Huanle , Lu Tianfeng , Xia Fanning , Lyu Jialan , Ma Jun , Kornberg Thomas B. , Zhang Qiang , Huang Hai 
Published: May 2022

AbstractAdult progenitor cells in the trachea of Drosophila larvae are activated and migrate out of niches when metamorphosis induces tracheal remodeling. Here we show that in response to metabolic deficiency in decaying tracheal branches, signaling by the insulin pathway controls the progenitor cells by regulating Yorkie (Yki)-dependent proliferation and migration. Yki, a transcription coactivator that is regulated by Hippo signaling, promotes transcriptional activation of cell cycle regulators and components of the extracellular matrix in tracheal progenitor cells. These findings reveal that regulation of Yki signaling by the insulin pathway governs proliferation and migration of tracheal progenitor cells, thereby identifying the regulatory mechanism by which metabolic depression drives progenitor cell activation and cell division that underlies tracheal remodeling.
Exceptionally high work density of a ferroelectric dynamic organic crystal around room temperature
Authors: Karothu Durga Prasad , Ferreira Rodrigo , Dushaq Ghada , Ahmed Ejaz , Catalano Luca , Halabi Jad Mahmoud , Alhaddad Zainab , Tahir Ibrahim , Li Liang , Mohamed Sharmarke , Rasras Mahmoud , Naumov Panče 
Published: May 2022

Abstract
Dynamic organic crystals are rapidly gaining traction as a new class of smart materials for energy conversion, however, they are only capable of very small strokes (<12%) and most of them operate through energetically cost-prohibitive processes at high temperatures. We report on the exceptional performance of an organic actuating material with exceedingly large stroke that can reversibly convert energy into work around room temperature. When transitioning at 295–305 K on heating and at 265–275 K on cooling the ferroelectric crystals of guanidinium nitrate exert a linear stroke of 51%, the highest value observed with a reversible operation of an organic single crystal actuator. Their maximum force density is higher than electric cylinders, ceramic piezoactuators, and electrostatic actuators, and their work capacity is close to that of thermal actuators. This work demonstrates the hitherto untapped potential of ionic organic crystals for applications such as light-weight capacitors, dielectrics, ferroelectric tunnel junctions, and thermistors.
Nanoparticle-enhanced radiotherapy synergizes with PD-L1 blockade to limit post-surgical cancer recurrence and metastasis
Authors: Guan Xin , Sun Liping , Shen Yuting , Jin Fengshan , Bo Xiaowan , Zhu Chunyan , Han Xiaoxia , Li Xiaolong , Chen Yu , Xu Huixiong , Yue Wenwen 
Published: May 2022

AbstractCancer recurrence after surgical resection (SR) is a considerable challenge, and the biological effect of SR on the tumor microenvironment (TME) that is pivotal in determining postsurgical treatment efficacy remains poorly understood. Here, with an experimental model, we demonstrate that the genomic landscape shaped by SR creates an immunosuppressive milieu characterized by hypoxia and high-influx of myeloid cells, fostering cancer progression and hindering PD-L1 blockade therapy. To address this issue, we engineer a radio-immunostimulant nanomedicine (IPI549@HMP) capable of targeting myeloid cells, and catalyzing endogenous H2O2 into O2 to achieve hypoxia-relieved radiotherapy (RT). The enhanced RT-mediated immunogenic effect results in postsurgical TME reprogramming and increased susceptibility to anti-PD-L1 therapy, which can suppress/eradicate locally residual and distant tumors, and elicits strong immune memory effects to resist tumor rechallenge. Our radioimmunotherapy points to a simple and effective therapeutic intervention against postsurgical cancer recurrence and metastasis.
A solar energy desalination analysis tool, sedat, with data and models for selecting technologies and regions
Authors: Fthenakis Vasilis , Yetman Gregory , Zhang Zhuoran , Squires John , Atia Adam A. , Alarcón-Padilla Diego-César , Palenzuela Patricia , Vicraman Vikas , Zaragoza Guillermo 
Published: May 2022

AbstractThere is interest for desalination technologies powered by solar energy as arid areas are typically bestowed with good solar potential. In response to a US DOE call for solar desalination analysis tools, we developed an open-source solar energy desalination analysis tool, sedat, for techno-economical evaluation of desalination technologies and selection of regions with the highest potential for using solar energy to power desalination plants. It is expected that this software will simplify the planning, design, and valuation of solar desalination systems in the U.S. and worldwide. Sedat uses Dash for integrating various layers of large volumes of GIS data with Python-based models of solar energy generation and desalination technologies. It derives time-series of energy generation and water production, with details of plant performance and suggestions for improving the solar-desalination coupling. This paper summarizes the various phases of the tool’s development, presents example results showing the potential, under multiple objectives, of solar desalination in parts of the U.S. southwest, and discusses method details that would be useful for future model development.
Incorporation of engineered nanoparticles of biochar and fly ash against bacterial leaf spot of pepper
Authors: Aftab Zill-e-Huma , Aslam Waqar , Aftab Arusa , Shah Adnan Noor , Akhter Adnan , Fakhar Usama , Siddiqui Iffat , Ahmed Waseem , Majid Farzana , Wróbel Jacek , Ali Muhammad Danish , Aftab Muzammil , Ahmed Mohamed A. A. , kalaji Hazem M. , Abbas Asad , Khalid Umar 
Published: May 2022

AbstractIn agriculture, the search for higher net profit is the main challenge in the economy of the producers and nano biochar attracts increasing interest in recent years due to its unique environmental behavior and increasing the productivity of plants by inducing resistance against phytopathogens. The effect of rice straw biochar and fly ash nanoparticles (RSBNPs and FNPs, respectively) in combination with compost soil on bacterial leaf spot of pepper caused by Xanthomonascampestris pv. vesicatoria was investigated both in vitro and in vivo. The application of nanoparticles as soil amendment significantly improved the chili pepper plant growth. However, RSBNPs were more effective in enhancing the above and belowground plant biomass production. Moreover, both RSBNPs and FNPs, significantly reduced (30.5 and 22.5%, respectively), while RSBNPs had shown in vitro growth inhibition of X.campestris pv. vesicatoria by more than 50%. The X-ray diffractometry of RSBNPs and FNPs highlighted the unique composition of nano forms which possibly contributed in enhancing the plant defence against invading X.campestris pv. vesicatoria. Based on our findings, it is suggested that biochar and fly ash nanoparticles can be used for reclaiming the problem soil and enhance crop productivity depending upon the nature of the soil and the pathosystem under investigation.
Development of β-carotene, lysine, and tryptophan-rich maize (Zea mays) inbreds through marker-assisted gene pyramiding
Authors: Chandrasekharan Neelima , Ramanathan Nagalakshmi , Pukalenthy Bharathi , Chandran Sarankumar , Manickam Dhasarathan , Adhimoolam Karthikeyan , Nalliappan Ganesan Kalipatty , Manickam Sudha , Rajasekaran Ravikesavan , Sampathrajan Vellaikumar , Muthusamy Vignesh , Hossain Firoz , Gupta Hari Shankar , Natesan Senthil 
Published: May 2022

AbstractMaize (Zea mays L.) is the leading cereal crop and staple food in many parts of the world. This study aims to develop nutrient-rich maize genotypes by incorporating crtRB1 and o2 genes associated with increased β-carotene, lysine, and tryptophan levels. UMI1200 and UMI1230, high quality maize inbreds, are well-adapted to tropical and semi-arid regions in India. However, they are deficient in β-carotene, lysine, and tryptophan. We used the concurrent stepwise transfer of genes by marker-assisted backcross breeding (MABB) scheme to introgress crtRB1 and o2 genes. In each generation (from F1, BC1F1–BC3F1, and ICF1–ICF3), foreground and background selections were carried out using gene-linked (crtRB1 3′TE and umc1066) and genome-wide simple sequence repeats (SSR) markers. Four independent BC3F1 lines of UMI1200 × CE477 (Cross-1), UMI1200 × VQL1 (Cross-2), UMI1230 × CE477 (Cross-3), and UMI1230 × VQL1 (Cross-4) having crtRB1 and o2 genes and 87.45–88.41% of recurrent parent genome recovery (RPGR) were intercrossed to generate the ICF1-ICF3 generations. Further, these gene pyramided lines were examined for agronomic performance and the β-carotene, lysine, and tryptophan contents. Six ICF3 lines (DBT-IC-β1σ4-4-8-8, DBT-IC-β1σ4-9-21-21, DBT-IC-β1σ4-10-1-1, DBT-IC-β2σ5-9-51-51, DBT-IC-β2σ5-9-52-52 and DBT-IC-β2σ5-9-53-53) possessing crtRB1 and o2 genes showed better agronomic performance (77.78–99.31% for DBT-IC-β1σ4 population and 85.71–99.51% for DBT-IC-β2σ5 population) like the recurrent parents and β-carotene (14.21–14.35 μg/g for DBT-IC-β1σ4 and 13.28–13.62 μg/g for DBT-IC-β2σ5), lysine (0.31–0.33% for DBT-IC-β1σ4 and 0.31–0.34% for DBT-IC-β2σ5), and tryptophan (0.079–0.082% for DBT-IC-β1σ4 and 0.078–0.083% for DBT-IC-β2σ5) levels on par with that of the donor parents. In the future, these improved lines could be developed as a cultivar for various agro-climatic zones and also as good genetic materials for maize nutritional breeding programs.