bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alpha-(1,6)-fucosyltransferase (FUT8) affects the survival strategy of osteosarcoma by remodeling TNF/NF-κB2 signaling
Authors: Lin Shanyi , Zhou Lenian , Dong Yang , Yang Qingcheng , Yang Quanjun , Jin Hanqiang , Yuan Ting , Zhou Shumin 
Published: December 2021

AbstractGlycosylation is an important modification of membrane proteins that results in functional changes in many cellular activities, from cell-cell recognition to regulatory signaling. Fucosyltransferase 8 (FUT8) is the sole enzyme responsible for core fucosylation, and aberrant fucosylation by dysregulated expression of fucosyltransferases is responsible for the growth of various types of carcinomas. However, the function of FUT8 in the progress of osteosarcoma (OS) has not been reported. In this study, we found that FUT8 is expressed at lower levels in patients with OS and in human OS cell lines such as MNNG/HOS, U2OS, and 143B, suggesting that attenuated expression of FUT8 is involved in the growth and progression of OS. Mechanistically, FUT8 affects the survival strategy of OS by modifying core-fucosylation levels of TNF receptors (TNFRs). Lower fucosylation of TNFRs activates the non-canonical NF-κB signaling pathway, and in turn, decreases mitochondria-dependent apoptosis in OS cells. Together, our results point to FUT8 being a negative regulator of OS that enhances OS-cell apoptosis and suggests a novel therapeutic strategy for treating OS.
Dynamic prostate cancer transcriptome analysis delineates the trajectory to disease progression
Authors: Bolis Marco , Bossi Daniela , Vallerga Arianna , Ceserani Valentina , Cavalli Manuela , Impellizzieri Daniela , Di Rito Laura , Zoni Eugenio , Mosole Simone , Elia Angela Rita , Rinaldi Andrea , Pereira Mestre Ricardo , D’Antonio Eugenia , Ferrari Matteo , Stoffel Flavio , Jermini Fernando , Gillessen Silke , Bubendorf Lukas , Schraml Peter , Calcinotto Arianna , Corey Eva , Moch Holger , Spahn Martin , Thalmann George , Kruithof-de Julio Marianna , Rubin Mark A. , Theurillat Jean-Philippe P. 
Published: December 2021

AbstractComprehensive genomic studies have delineated key driver mutations linked to disease progression for most cancers. However, corresponding transcriptional changes remain largely elusive because of the bias associated with cross-study analysis. Here, we overcome these hurdles and generate a comprehensive prostate cancer transcriptome atlas that describes the roadmap to tumor progression in a qualitative and quantitative manner. Most cancers follow a uniform trajectory characterized by upregulation of polycomb-repressive-complex-2, G2-M checkpoints, and M2 macrophage polarization. Using patient-derived xenograft models, we functionally validate our observations and add single-cell resolution. Thereby, we show that tumor progression occurs through transcriptional adaption rather than a selection of pre-existing cancer cell clusters. Moreover, we determine at the single-cell level how inhibition of EZH2 - the top upregulated gene along the trajectory – reverts tumor progression and macrophage polarization. Finally, a user-friendly web-resource is provided enabling the investigation of dynamic transcriptional perturbations linked to disease progression.
Ezh2 is essential for the generation of functional yolk sac derived erythro-myeloid progenitors
Authors: Neo Wen Hao , Meng Yiran , Rodriguez-Meira Alba , Fadlullah Muhammad Z. H. , Booth Christopher A. G. , Azzoni Emanuele , Thongjuea Supat , de Bruijn Marella F. T. R. , Jacobsen Sten Eirik W. , Mead Adam J. , Lacaud Georges 
Published: December 2021

AbstractYolk sac (YS) hematopoiesis is critical for the survival of the embryo and a major source of tissue-resident macrophages that persist into adulthood. Yet, the transcriptional and epigenetic regulation of YS hematopoiesis remains poorly characterized. Here we report that the epigenetic regulator Ezh2 is essential for YS hematopoiesis but dispensable for subsequent aorta–gonad–mesonephros (AGM) blood development. Loss of EZH2 activity in hemogenic endothelium (HE) leads to the generation of phenotypically intact but functionally deficient erythro-myeloid progenitors (EMPs), while the generation of primitive erythroid cells is not affected. EZH2 activity is critical for the generation of functional EMPs at the onset of the endothelial-to-hematopoietic transition but subsequently dispensable. We identify a lack of Wnt signaling downregulation as the primary reason for the production of non-functional EMPs. Together, our findings demonstrate a critical and stage-specific role of Ezh2 in modulating Wnt signaling during the generation of EMPs from YS HE.
Catalytic flexibility of rice glycosyltransferase OsUGT91C1 for the production of palatable steviol glycosides
Authors: Zhang Jinzhu , Tang Minghai , Chen Yujie , Ke Dan , Zhou Jie , Xu Xinyu , Yang Wenxian , He Jianxiong , Dong Haohao , Wei Yuquan , Naismith James H. , Lin Yi , Zhu Xiaofeng , Cheng Wei 
Published: December 2021

AbstractSteviol glycosides are the intensely sweet components of extracts from Stevia rebaudiana. These molecules comprise an invariant steviol aglycone decorated with variable glycans and could widely serve as a low-calorie sweetener. However, the most desirable steviol glycosides Reb D and Reb M, devoid of unpleasant aftertaste, are naturally produced only in trace amounts due to low levels of specific β (1–2) glucosylation in Stevia. Here, we report the biochemical and structural characterization of OsUGT91C1, a glycosyltransferase from Oryza sativa, which is efficient at catalyzing β (1–2) glucosylation. The enzyme’s ability to bind steviol glycoside substrate in three modes underlies its flexibility to catalyze β (1–2) glucosylation in two distinct orientations as well as β (1–6) glucosylation. Guided by the structural insights, we engineer this enzyme to enhance the desirable β (1–2) glucosylation, eliminate β (1–6) glucosylation, and obtain a promising catalyst for the industrial production of naturally rare but palatable steviol glycosides.
Global patterns of potential future plant diversity hidden in soil seed banks
Authors: Yang Xuejun , Baskin Carol C. , Baskin Jerry M. , Pakeman Robin J. , Huang Zhenying , Gao Ruiru , Cornelissen Johannes H. C. 
Published: December 2021

AbstractSoil seed banks represent a critical but hidden stock for potential future plant diversity on Earth. Here we compiled and analyzed a global dataset consisting of 15,698 records of species diversity and density for soil seed banks in natural plant communities worldwide to quantify their environmental determinants and global patterns. Random forest models showed that absolute latitude was an important predictor for diversity of soil seed banks. Further, climate and soil were the major determinants of seed bank diversity, while net primary productivity and soil characteristics were the main predictors of seed bank density. Moreover, global mapping revealed clear spatial patterns for soil seed banks worldwide; for instance, low densities may render currently species-rich low latitude biomes (such as tropical rain-forests) less resilient to major disturbances. Our assessment provides quantitative evidence of how environmental conditions shape the distribution of soil seed banks, which enables a more accurate prediction of the resilience and vulnerabilities of plant communities and biomes under global changes.
Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro
Authors: Garcia-Alonso Luz , Handfield Louis-François , Roberts Kenny , Nikolakopoulou Konstantina , Fernando Ridma C. , Gardner Lucy , Woodhams Benjamin , Arutyunyan Anna , Polanski Krzysztof , Hoo Regina , Sancho-Serra Carmen , Li Tong , Kwakwa Kwasi , Tuck Elizabeth , Lorenzi Valentina , Massalha Hassan , Prete Martin , Kleshchevnikov Vitalii , Tarkowska Aleksandra , Porter Tarryn , Mazzeo Cecilia Icoresi , van Dongen Stijn , Dabrowska Monika , Vaskivskyi Vasyl , Mahbubani Krishnaa T. , Park Jong-eun , Jimenez-Linan Mercedes , Campos Lia , Kiselev Vladimir Yu. , Lindskog Cecilia , Ayuk Paul , Prigmore Elena , Stratton Michael R. , Saeb-Parsy Kourosh , Moffett Ashley , Moore Luiza , Bayraktar Omer A. , Teichmann Sarah A. , Turco Margherita Y. , Vento-Tormo Roser 
Published: December 2021

AbstractThe endometrium, the mucosal lining of the uterus, undergoes dynamic changes throughout the menstrual cycle in response to ovarian hormones. We have generated dense single-cell and spatial reference maps of the human uterus and three-dimensional endometrial organoid cultures. We dissect the signaling pathways that determine cell fate of the epithelial lineages in the lumenal and glandular microenvironments. Our benchmark of the endometrial organoids reveals the pathways and cell states regulating differentiation of the secretory and ciliated lineages both in vivo and in vitro. In vitro downregulation of WNT or NOTCH pathways increases the differentiation efficiency along the secretory and ciliated lineages, respectively. We utilize our cellular maps to deconvolute bulk data from endometrial cancers and endometriotic lesions, illuminating the cell types dominating in each of these disorders. These mechanistic insights provide a platform for future development of treatments for common conditions including endometriosis and endometrial carcinoma.
A cortical circuit for audio-visual predictions
Authors: Garner Aleena R. , Keller Georg B. 
Published: December 2021

AbstractLearned associations between stimuli in different sensory modalities can shape the way we perceive these stimuli. However, it is not well understood how these interactions are mediated or at what level of the processing hierarchy they occur. Here we describe a neural mechanism by which an auditory input can shape visual representations of behaviorally relevant stimuli through direct interactions between auditory and visual cortices in mice. We show that the association of an auditory stimulus with a visual stimulus in a behaviorally relevant context leads to experience-dependent suppression of visual responses in primary visual cortex (V1). Auditory cortex axons carry a mixture of auditory and retinotopically matched visual input to V1, and optogenetic stimulation of these axons selectively suppresses V1 neurons that are responsive to the associated visual stimulus after, but not before, learning. Our results suggest that cross-modal associations can be communicated by long-range cortical connections and that, with learning, these cross-modal connections function to suppress responses to predictable input.
Multiscale interactome analysis coupled with off-target drug predictions reveals drug repurposing candidates for human coronavirus disease
Authors: Sugiyama Michael G. , Cui Haotian , Redka Dar’ya S. , Karimzadeh Mehran , Rujas Edurne , Maan Hassaan , Hayat Sikander , Cheung Kyle , Misra Rahul , McPhee Joseph B. , Viirre Russell D. , Haller Andrew , Botelho Roberto J. , Karshafian Raffi , Sabatinos Sarah A. , Fairn Gregory D. , Madani Tonekaboni Seyed Ali , Windemuth Andreas , Julien Jean-Philippe , Shahani Vijay , MacKinnon Stephen S. , Wang Bo , Antonescu Costin N. 
Published: December 2021

AbstractThe COVID-19 pandemic has highlighted the urgent need for the identification of new antiviral drug therapies for a variety of diseases. COVID-19 is caused by infection with the human coronavirus SARS-CoV-2, while other related human coronaviruses cause diseases ranging from severe respiratory infections to the common cold. We developed a computational approach to identify new antiviral drug targets and repurpose clinically-relevant drug compounds for the treatment of a range of human coronavirus diseases. Our approach is based on graph convolutional networks (GCN) and involves multiscale host-virus interactome analysis coupled to off-target drug predictions. Cell-based experimental assessment reveals several clinically-relevant drug repurposing candidates predicted by the in silico analyses to have antiviral activity against human coronavirus infection. In particular, we identify the MET inhibitor capmatinib as having potent and broad antiviral activity against several coronaviruses in a MET-independent manner, as well as novel roles for host cell proteins such as IRAK1/4 in supporting human coronavirus infection, which can inform further drug discovery studies.
An Italian dinosaur Lagerstätte reveals the tempo and mode of hadrosauriform body size evolution
Authors: Chiarenza Alfio Alessandro , Fabbri Matteo , Consorti Lorenzo , Muscioni Marco , Evans David C. , Cantalapiedra Juan L. , Fanti Federico 
Published: December 2021

AbstractDuring the latest Cretaceous, the European Archipelago was characterized by highly fragmented landmasses hosting putative dwarfed, insular dinosaurs, claimed as fossil evidence of the “island rule”. The Villaggio del Pescatore quarry (north-eastern Italy) stands as the most informative locality within the palaeo-Mediterranean region and represents the first, multi-individual Konservat-Lagerstätte type dinosaur-bearing locality in Italy. The site is here critically re-evaluated as early Campanian in age, thus preceding the final fragmentation stages of the European Archipelago, including all other European localities preserving hypothesized dwarfed taxa. New skeletal remains allowed osteohistological analyses on the hadrosauroid Tethyshadros insularis indicating subadult features in the type specimen whereas a second, herein newly described, larger individual is likely somatically mature. A phylogenetic comparative framework places the body-size of T. insularis in range with other non-hadrosaurid Eurasian hadrosauroids, rejecting any significant evolutionary trend towards miniaturisation in this clade, confuting its ‘pygmy’ status, and providing unmatched data to infer environmentally-driven body-size trends in Mesozoic dinosaurs.
A plasmonic gold nanofilm-based microfluidic chip for rapid and inexpensive droplet-based photonic PCR
Authors: Jalili Abbas , Bagheri Maryam , Shamloo Amir , Kazemipour Ashkezari Amir Hossein 
Published: December 2021

AbstractPolymerase chain reaction (PCR) is a powerful tool for nucleic acid amplification and quantification. However, long thermocycling time is a major limitation of the commercial PCR devices in the point-of-care (POC). Herein, we have developed a rapid droplet-based photonic PCR (dpPCR) system, including a gold (Au) nanofilm-based microfluidic chip and a plasmonic photothermal cycler. The chip is fabricated by adding mineral oil to uncured polydimethylsiloxane (PDMS) to suppress droplet evaporation in PDMS microfluidic chips during PCR thermocycling. A PDMS to gold bonding technique using a double-sided adhesive tape is applied to enhance the bonding strength between the oil-added PDMS and the gold nanofilm. Moreover, the gold nanofilm excited by two light-emitting diodes (LEDs) from the top and bottom sides of the chip provides fast heating of the PCR sample to 230 °C within 100 s. Such a design enables 30 thermal cycles from 60 to 95 °C within 13 min with the average heating and cooling rates of 7.37 ± 0.27 °C/s and 1.91 ± 0.03 °C/s, respectively. The experimental results demonstrate successful PCR amplification of the alcohol oxidase (AOX) gene using the rapid plasmonic photothermal cycler and exhibit the great performance of the microfluidic chip for droplet-based PCR.
Fractal grid-induced turbulence strength characterization via piezoelectric thin-film flapping velocimetry
Authors: Lee Ted Sian , Ooi Ean Hin , Chang Wei Sea , Foo Ji Jinn 
Published: December 2021

AbstractThe centerline streamwise and cross-sectional (x/Dh = 0.425) turbulence characteristics of a 2D planar space-filling square-fractal-grid (SFG) composed of self-similar patterns superimposed at multiple length-scales is experimentally unveiled via piezoelectric thin-film flapping velocimetry (PTFV). The fluid–structure-interaction between a flexible piezoelectric thin-film and SFG-generated turbulent flow at ReDh = 4.1 × 104 is investigated by analysis of the thin-film’s mechanical response. Measurements of the thin-film-tip deflection δ and induced voltage V demonstrate increasing flow fluctuation strength in the turbulence generation region, followed by rapid decay further downstream of the SFG. Interestingly, SFG-induced turbulence enables the generation of maximum centerline thin-film’s response (Vrms, δrms) and millinewton turbulence-forcing (turbulence-induced excitation force acting on the thin-film) Frms which are respectively, 7× and 2× larger than the classical square-regular-grid of similar blockage ratio. The low frequency, large-scale energy-containing eddies at SFG’s central opening plays a critical role in driving the thin-film vibration. Most importantly, the SFG-generated turbulence at (y/T = 0.106, z/T = 0.125) away from the centerline allows equivalent mechanical characteristics of turbulence generation and decay, with peak of 1.9× nearer from grid. In short, PTFV provides a unique expression of the SFG-generated turbulence, of which, the equivalent turbulence length-scale and induced-forcing deduced could aid in deciphering the flow dynamics for effective turbulence management.
Bone density and genomic analysis unfold cold adaptation mechanisms of ancient inhabitants of Tierra del Fuego
Authors: Watanabe Mikiko , Risi Renata , Tafuri Mary Anne , Silvestri Valentina , D’Andrea Daniel , Raimondo Domenico , Rea Sandra , Di Vincenzo Fabio , Profico Antonio , Tuccinardi Dario , Sciuto Rosa , Basciani Sabrina , Mariani Stefania , Lubrano Carla , Cinti Saverio , Ottini Laura , Manzi Giorgio , Gnessi Lucio 
Published: December 2021

AbstractThe Fuegians, ancient inhabitants of Tierra del Fuego, are an exemplary case of a cold-adapted population, since they were capable of living in extreme climatic conditions without any adequate clothing. However, the mechanisms of their extraordinary resistance to cold remain enigmatic. Brown adipose tissue (BAT) plays a crucial role in this kind of adaptation, besides having a protective role on the detrimental effect of low temperatures on bone structure. Skeletal remains of 12 adult Fuegians, collected in the second half of XIX century, were analyzed for bone mineral density and structure. We show that, despite the unfavorable climate, bone mineral density of Fuegians was close to that seen in modern humans living in temperate zones. Furthermore, we report significant differences between Fuegians and other cold-adapted populations in the frequency of the Homeobox protein Hox-C4 (HOXC4) rs190771160 variant, a gene involved in BAT differentiation, whose identified variant is predicted to upregulate HOXC4 expression. Greater BAT accumulation might therefore explain the Fuegians extreme cold-resistance and the protection against major cold-related damage. These results increase our understanding of how ecological challenges have been important drivers of human–environment interactions during Humankind history.
Electrosynthesis of S-thiocarbamates with disulfides as a sulfur source
Authors: Liu Xiaoying , Cai Tian-Cheng , Guo Dingyi , Nong Zhibin , Yang Yujie , Li Qiang , Jiang Hongmei , Liu Xingru , Gui Qing-Wen 
Published: December 2021

An electrochemical oxidative synthesis of S-thiocarbamates via a three-component coupling reaction (disulfide, water and isocyanide) is developed, which avoids the use of external oxidants and generates only hydrogen gas as the by-product.
A BiLSTM cardinality estimator in complex database systems based on attention mechanism
Authors: Zhou Qiang , Yang Guoping , Song Haiquan , Guo Jin , Zhang Yadong , Wei Shengjie , Qu Lulu , Gutierrez Louis Alberto , Qiao Shaojie 
Published: December 2021

AbstractAn excellent cardinality estimation can make the query optimiser produce a good execution plan. Although there are some studies on cardinality estimation, the prediction results of existing cardinality estimators are inaccurate and the query efficiency cannot be guaranteed as well. In particular, they are difficult to accurately obtain the complex relationships between multiple tables in complex database systems. When dealing with complex queries, the existing cardinality estimators cannot achieve good results. In this study, a novel cardinality estimator is proposed. It uses the core techniques with the BiLSTM network structure and adds the attention mechanism. First, the columns involved in the query statements in the training set are sampled and compressed into bitmaps. Then, the Word2vec model is used to embed the word vectors about the query statements. Finally, the BiLSTM network and attention mechanism are employed to deal with word vectors. The proposed model takes into consideration not only the correlation between tables but also the processing of complex predicates. Extensive experiments and the evaluation of BiLSTM‐Attention Cardinality Estimator (BACE) on the IMDB datasets are conducted. The results show that the deep learning model can significantly improve the quality of cardinality estimation, which is a vital role in query optimisation for complex databases.
Linear modelling of series FACTS devices in power system operation models
Authors: Rui Xinyang , Sahraei‐Ardakani Mostafa , Nudell Thomas R. 
Published: December 2021

AbstractThis paper presents injection‐shift‐factor‐based linear modelling for various types of series flexible ac transmission system (FACTS) devices within the DC power flow framework. The presented models allow FACTS devices to be properly integrated in current operation and planning software tools, which is key to harnessing the power flow capabilities provided by FACTS technology. Although recent literature has attempted to develop linear models for FACTS devices, the existing models do not accurately reflect the actual operating range for many FACTS devices. Compared to the existing models, the modelling approach presented here reflects the principle of operation of each type of series FACTS device in adjusting transmission line reactance. Through mathematical derivation, linear constraints for FACTS operation are formulated, which are used to formulate power system operation models. The formulated problems are then analysed through simulation studies on various test systems. The results highlight the significant computational efficiency improvements provided by linear FACTS modelling in DC‐based operation models.
Mechanism on improved surface flashover performances in vacuum of epoxy resin using fluorocarbon plasma treatment
Authors: Chen Sile , Cheng Tao , Chen Zhaoquan , Zhang Guanjun 
Published: December 2021

AbstractTo improve the insulation, strength of materials is a permanent topic in the fields of high voltage and insulation, and surface insulation is one of the difficulties. Research shows that the surface fluorination by a non‐equilibrium plasma is a promising method to enhance the surface flashover characteristics of insulating materials. However, the determinants of flashover characteristics are so many that the mechanism is not well known. This paper aims to find out the reasons for the surface insulation improvement and optimise the plasma process parameters. The epoxy resin surfaces are modified by a fluorocarbon plasma, and the flashover voltages in vacuum and secondary electron emission yield are tested experimentally. Combined with the state of the art and the authors' previous work, the mechanism of improved surface flashover performances is investigated in depth from three aspects: the plasma process parameters, the surface physical and chemical properties and the surface electrical performances. A comprehensive understanding of the mechanism is concluded, of which the whole processes from the plasma surface modification of materials to the surface insulation performances are taken into account. It is hopeful to promote the practical applications of plasma fluorination in electrical engineering through the findings of this paper.