bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exosomes in ovarian cancer ascites promote epithelial–mesenchymal transition of ovarian cancer cells by delivery of miR-6780b-5p
Authors: Cai Jing , Gong Lanqing , Li Guodong , Guo Jing , Yi Xiaoqing , Wang Zehua 
Published: February 2021

AbstractThe poor prognosis of ovarian cancer is mainly due to metastasis, and the specific mechanism underlying ovarian cancer metastasis is not clear. Ascites-derived exosomes (ADEs) play an important role in the progression of ovarian cancer, but the mechanism is unknown. Here, we found that ADEs promoted ovarian cancer metastasis not only in vitro but also in vivo. This promotive function was based on epithelial–mesenchymal transition (EMT) of ovarian cancer cells. Bioinformatics analysis of RNA sequencing microarray data indicated that miR-6780b-5p may be the key microRNA (miRNA) in ADEs that facilitates cancer metastasis. Moreover, the expression of exosomal miR-6780b-5p correlated with tumor metastasis in ovarian cancer patients. miR-6780b-5p overexpression promoted and miR-6780b-5p downregulation suppressed EMT of ovarian cancer cells. These results suggest that ADEs transfer miR-6780b-5p to ovarian cancer cells, promoting EMT and finally facilitating ovarian cancer metastasis.
CircRNAs: a new target for the diagnosis and treatment of digestive system neoplasms
Authors: Li Jie , Xu Qiang , Huang Zi-jian , Mao Ning , Lin Zhi-tao , Cheng Long , Sun Bei , Wang Gang 
Published: February 2021

AbstractA circRNA is a type of endogenous noncoding RNA that consists of a closed circular RNA molecule formed by reverse splicing; these RNAs are widely distributed in a variety of biological cells. In contrast to linear RNAs, circRNAs have no 5′ cap or 3′ poly(A) tail. They have a stable structure, a high degree of conservation, and high stability, and they are richly and specifically expressed in certain tissues and developmental stages. CircRNAs play a very important role in the occurrence and progression of malignant tumors. According to their origins, circRNAs can be divided into four types: exon-derived circRNAs (ecRNAs), intron-derived circRNAs (ciRNAs), circRNAs containing both exons and introns (EIciRNAs) and intergenic circRNAs. A large number of studies have shown that circRNAs have a variety of biological functions, participate in the regulation of gene expression and play an important role in the occurrence and progression of tumors. In this paper, the structure and function of circRNAs are reviewed, along with their biological role in malignant tumors of the digestive tract, in order to provide a reference for the diagnosis and treatment of digestive system neoplasms.
Suppression of steroid 5α-reductase type I promotes cellular apoptosis and autophagy via PI3K/Akt/mTOR pathway in multiple myeloma
Authors: Dou Renjie , Qian Jinjun , Wu Wei , Zhang Yanxin , Yuan Yuxia , Guo Mengjie , Wei Rongfang , Yang Shu , Jurczyszyn Artur , Janz Siegfried , Beksac Meral , Gu Chunyan , Yang Ye 
Published: February 2021

AbstractSteroid 5α-reductase type I (SRD5A1) is a validated oncogene in many sex hormone-related cancers, but its role in multiple myeloma (MM) remains unknown. Based on gene expression profiling (GEP) of sequential MM samples during the disease course, we found that the aberrant expression of SRD5A1 was correlated with progression and poor prognosis in MM patients. In this study, the oncogenic roles of SRD5A1 were validated in human MM cell lines (ARP1 and H929) and the xenograft MM model as well as the 5TMM mouse model. MTT and flow cytometry were used to assess MM cell proliferation, cell cycle, and apoptosis post inducible knockdown SRD5A1 by lentivirus-mediated short-hairpin RNA (shRNA). Transcriptomic sequencing, immunofluorescence, and western blot were used to investigate the effects of SRD5A1 suppression on cell apoptosis and autophagy. Mechanistically, SRD5A1 downregulation simultaneously regulated both the Bcl-2 family protein-mediated apoptosis and the autophagic process via PI3K/Akt/mTOR signaling pathway in MM cells. Meanwhile, the autophagy inhibitor (3-methyladenine) and SRD5A1 inhibitor (Dutasteride) were utilized to evaluate their anti-myeloma effect. Thus, our results demonstrated that SRD5A1 downregulation simultaneously regulated both the apoptosis and the autophagic process in MM cells. The dual autophagy–apoptosis regulatory SRD5A1 may serve as a biomarker and potential target for MM progression and prognosis.
A superconducting switch actuated by injection of high-energy electrons
Authors: Ritter M. F. , Fuhrer A. , Haxell D. Z. , Hart S. , Gumann P. , Riel H. , Nichele F. 
Published: February 2021

AbstractRecent experiments with metallic nanowires devices seem to indicate that superconductivity can be controlled by the application of electric fields. In such experiments, critical currents are tuned and eventually suppressed by relatively small voltages applied to nearby gate electrodes, at odds with current understanding of electrostatic screening in metals. We investigate the impact of gate voltages on superconductivity in similar metal nanowires. Varying materials and device geometries, we study the physical mechanism behind the quench of superconductivity. We demonstrate that the transition from superconducting to resistive state can be understood in detail by tunneling of high-energy electrons from the gate contact to the nanowire, resulting in quasiparticle generation and, at sufficiently large currents, heating. Onset of critical current suppression occurs below gate currents of 100fA, which are challenging to detect in typical experiments.
Flexible categorization in perceptual decision making
Authors: Prat-Ortega Genís , Wimmer Klaus , Roxin Alex , de la Rocha Jaime 
Published: February 2021

AbstractPerceptual decisions rely on accumulating sensory evidence. This computation has been studied using either drift diffusion models or neurobiological network models exhibiting winner-take-all attractor dynamics. Although both models can account for a large amount of data, it remains unclear whether their dynamics are qualitatively equivalent. Here we show that in the attractor model, but not in the drift diffusion model, an increase in the stimulus fluctuations or the stimulus duration promotes transitions between decision states. The increase in the number of transitions leads to a crossover between weighting mostly early evidence (primacy) to weighting late evidence (recency), a prediction we validate with psychophysical data. Between these two limiting cases, we found a novel flexible categorization regime, in which fluctuations can reverse initially-incorrect categorizations. This reversal asymmetry results in a non-monotonic psychometric curve, a distinctive feature of the attractor model. Our findings point to correcting decision reversals as an important feature of perceptual decision making.
Spatially mapped single-cell chromatin accessibility
Authors: Thornton Casey A. , Mulqueen Ryan M. , Torkenczy Kristof A. , Nishida Andrew , Lowenstein Eve G. , Fields Andrew J. , Steemers Frank J. , Zhang Wenri , McConnell Heather L. , Woltjer Randy L. , Mishra Anusha , Wright Kevin M. , Adey Andrew C. 
Published: February 2021

AbstractHigh-throughput single-cell epigenomic assays can resolve cell type heterogeneity in complex tissues, however, spatial orientation is lost. Here, we present single-cell combinatorial indexing on Microbiopsies Assigned to Positions for the Assay for Transposase Accessible Chromatin, or sciMAP-ATAC, as a method for highly scalable, spatially resolved, single-cell profiling of chromatin states. sciMAP-ATAC produces data of equivalent quality to non-spatial sci-ATAC and retains the positional information of each cell within a 214 micron cubic region, with up to hundreds of tracked positions in a single experiment. We apply sciMAP-ATAC to assess cortical lamination in the adult mouse primary somatosensory cortex and in the human primary visual cortex, where we produce spatial trajectories and integrate our data with non-spatial single-nucleus RNA and other chromatin accessibility single-cell datasets. Finally, we characterize the spatially progressive nature of cerebral ischemic infarction in the mouse brain using a model of transient middle cerebral artery occlusion.
The secreted endoribonuclease ENDU-2 from the soma protects germline immortality in C. elegans
Authors: Qi Wenjing , Gromoff Erika D. V. , Xu Fan , Zhao Qian , Yang Wei , Pfeifer Dietmar , Maier Wolfgang , Long Lijiang , Baumeister Ralf 
Published: February 2021

AbstractMulticellular organisms coordinate tissue specific responses to environmental information via both cell-autonomous and non-autonomous mechanisms. In addition to secreted ligands, recent reports implicated release of small RNAs in regulating gene expression across tissue boundaries. Here, we show that the conserved poly-U specific endoribonuclease ENDU-2 in C. elegans is secreted from the soma and taken-up by the germline to ensure germline immortality at elevated temperature. ENDU-2 binds to mature mRNAs and negatively regulates mRNA abundance both in the soma and the germline. While ENDU-2 promotes RNA decay in the soma directly via its endoribonuclease activity, ENDU-2 prevents misexpression of soma-specific genes in the germline and preserves germline immortality independent of its RNA-cleavage activity. In summary, our results suggest that the secreted RNase ENDU-2 regulates gene expression across tissue boundaries in response to temperature alterations and contributes to maintenance of stem cell immortality, probably via retaining a stem cell specific program of gene expression.
Accelerating target deconvolution for therapeutic antibody candidates using highly parallelized genome editing
Authors: Mattsson Jenny , Ekdahl Ludvig , Junghus Fredrik , Ajore Ram , Erlandsson Eva , Niroula Abhishek , Pertesi Maroulio , Frendéus Björn , Teige Ingrid , Nilsson Björn 
Published: February 2021

AbstractTherapeutic antibodies are transforming the treatment of cancer and autoimmune diseases. Today, a key challenge is finding antibodies against new targets. Phenotypic discovery promises to achieve this by enabling discovery of antibodies with therapeutic potential without specifying the molecular target a priori. Yet, deconvoluting the targets of phenotypically discovered antibodies remains a bottleneck; efficient deconvolution methods are needed for phenotypic discovery to reach its full potential. Here, we report a comprehensive investigation of a target deconvolution approach based on pooled CRISPR/Cas9. Applying this approach within three real-world phenotypic discovery programs, we rapidly deconvolute the targets of 38 of 39 test antibodies (97%), a success rate far higher than with existing approaches. Moreover, the approach scales well, requires much less work, and robustly identifies antibodies against the major histocompatibility complex. Our data establish CRISPR/Cas9 as a highly efficient target deconvolution approach, with immediate implications for the development of antibody-based drugs.
Interaction of 7SK with the Smn complex modulates snRNP production
Authors: Ji Changhe , Bader Jakob , Ramanathan Pradhipa , Hennlein Luisa , Meissner Felix , Jablonka Sibylle , Mann Matthias , Fischer Utz , Sendtner Michael , Briese Michael 
Published: February 2021

AbstractGene expression requires tight coordination of the molecular machineries that mediate transcription and splicing. While the interplay between transcription kinetics and spliceosome fidelity has been investigated before, less is known about mechanisms regulating the assembly of the spliceosomal machinery in response to transcription changes. Here, we report an association of the Smn complex, which mediates spliceosomal snRNP biogenesis, with the 7SK complex involved in transcriptional regulation. We found that Smn interacts with the 7SK core components Larp7 and Mepce and specifically associates with 7SK subcomplexes containing hnRNP R. The association between Smn and 7SK complexes is enhanced upon transcriptional inhibition leading to reduced production of snRNPs. Taken together, our findings reveal a functional association of Smn and 7SK complexes that is governed by global changes in transcription. Thus, in addition to its canonical nuclear role in transcriptional regulation, 7SK has cytosolic functions in fine-tuning spliceosome production according to transcriptional demand.
Strand-specific single-cell methylomics reveals distinct modes of DNA demethylation dynamics during early mammalian development
Authors: Sen Maya , Mooijman Dylan , Chialastri Alex , Boisset Jean-Charles , Popovic Mina , Heindryckx Björn , Chuva de Sousa Lopes Susana M. , Dey Siddharth S. , van Oudenaarden Alexander 
Published: February 2021

AbstractDNA methylation (5mC) is central to cellular identity. The global erasure of 5mC from the parental genomes during preimplantation mammalian development is critical to reset the methylome of gametes to the cells in the blastocyst. While active and passive modes of demethylation have both been suggested to play a role in this process, the relative contribution of these two mechanisms to 5mC erasure remains unclear. Here, we report a single-cell method (scMspJI-seq) that enables strand-specific quantification of 5mC, allowing us to systematically probe the dynamics of global demethylation. When applied to mouse embryonic stem cells, we identified substantial cell-to-cell strand-specific 5mC heterogeneity, with a small group of cells displaying asymmetric levels of 5mCpG between the two DNA strands of a chromosome suggesting loss of maintenance methylation. Next, in preimplantation mouse embryos, we discovered that methylation maintenance is active till the 16-cell stage followed by passive demethylation in a fraction of cells within the early blastocyst at the 32-cell stage of development. Finally, human preimplantation embryos qualitatively show temporally delayed yet similar demethylation dynamics as mouse embryos. Collectively, these results demonstrate that scMspJI-seq is a sensitive and cost-effective method to map the strand-specific genome-wide patterns of 5mC in single cells.
Sialic acids in pancreatic cancer cells drive tumour-associated macrophage differentiation via the Siglec receptors Siglec-7 and Siglec-9
Authors: Rodriguez Ernesto , Boelaars Kelly , Brown Kari , Eveline Li R. J. , Kruijssen Laura , Bruijns Sven C. M. , van Ee Thomas , Schetters Sjoerd T. T. , Crommentuijn Matheus H. W. , van der Horst Joost C. , van Grieken Nicole C. T. , van Vliet Sandra J. , Kazemier Geert , Giovannetti Elisa , Garcia-Vallejo Juan J. , van Kooyk Yvette 
Published: February 2021

AbstractChanges in glycosylation during tumour progression are a key hallmark of cancer. One of the glycan moieties generally overexpressed in cancer are sialic acids, which can induce immunomodulatory properties via binding to Siglec receptors. We here show that Pancreatic Ductal Adenocarcinoma (PDAC) tumour cells present an increased sialylation that can be recognized by Siglec-7 and Siglec-9 on myeloid cells. We identified the expression of the α2,3 sialyltransferases ST3GAL1 and ST3GAL4 as main contributor to the synthesis of ligands for Siglec-7 and Siglec-9 in tumour cells. Analysing the myeloid composition in PDAC, using single cell and bulk transcriptomics data, we identified monocyte-derived macrophages as contributors to the poor clinical outcome. Tumour-derived sialic acids dictate monocyte to macrophage differentiation via signalling through Siglec-7 and Siglec-9. Moreover, triggering of Siglec-9 in macrophages reduce inflammatory programmes, while increasing PD-L1 and IL-10 expression, illustrating that sialic acids modulate different myeloid cells. This work highlights a critical role for sialylated glycans in controlling immune suppression and provides new potential targets for cancer immunotherapy in PDAC.
Quantifying information accumulation encoded in the dynamics of biochemical signaling
Authors: Tang Ying , Adelaja Adewunmi , Ye Felix X.-F. , Deeds Eric , Wollman Roy , Hoffmann Alexander 
Published: February 2021

AbstractCellular responses to environmental changes are encoded in the complex temporal patterns of signaling proteins. However, quantifying the accumulation of information over time to direct cellular decision-making remains an unsolved challenge. This is, in part, due to the combinatorial explosion of possible configurations that need to be evaluated for information in time-course measurements. Here, we develop a quantitative framework, based on inferred trajectory probabilities, to calculate the mutual information encoded in signaling dynamics while accounting for cell-cell variability. We use it to understand NFκB transcriptional dynamics in response to different immune threats, and reveal that some threats are distinguished faster than others. Our analyses also suggest specific temporal phases during which information distinguishing threats becomes available to immune response genes; one specific phase could be mapped to the functionality of the IκBα negative feedback circuit. The framework is generally applicable to single-cell time series measurements, and enables understanding how temporal regulatory codes transmit information over time.
Probing intramolecular vibronic coupling through vibronic-state imaging
Authors: Kong Fan-Fang , Tian Xiao-Jun , Zhang Yang , Yu Yun-Jie , Jing Shi-Hao , Zhang Yao , Tian Guang-Jun , Luo Yi , Yang Jin-Long , Dong Zhen-Chao , Hou J. G. 
Published: February 2021

AbstractVibronic coupling is a central issue in molecular spectroscopy. Here we investigate vibronic coupling within a single pentacene molecule in real space by imaging the spatial distribution of single-molecule electroluminescence via highly localized excitation of tunneling electrons in a controlled plasmonic junction. The observed two-spot orientation for certain vibronic-state imaging is found to be evidently different from the purely electronic 0–0 transition, rotated by 90°, which reflects the change in the transition dipole orientation from along the molecular short axis to the long axis. Such a change reveals the occurrence of strong vibronic coupling associated with a large Herzberg–Teller contribution, going beyond the conventional Franck–Condon picture. The emergence of large vibration-induced transition charges oscillating along the long axis is found to originate from the strong dynamic perturbation of the anti-symmetric vibration on those carbon atoms with large transition density populations during electronic transitions.
Proteolysis-targeting chimera against BCL-XL destroys tumor-infiltrating regulatory T cells
Authors: Kolb Ryan , De Umasankar , Khan Sajid , Luo Yuewan , Kim Myung-Chul , Yu Haijun , Wu Chaoyan , Mo Jiao , Zhang Xin , Zhang Peiyi , Zhang Xuan , Borcherding Nicholas , Koppel Daniel , Fu Yang-Xin , Zheng Song Guo , Avram Dorina , Zheng Guangrong , Zhou Daohong , Zhang Weizhou 
Published: February 2021

AbstractRegulatory T cells (Tregs) play an important role in maintaining immune homeostasis and, within tumors, their upregulation is common and promotes an immunosuppressive microenvironment. Therapeutic strategies that can eliminate Tregs in the tumor (i.e., therapies that do not run the risk of affecting normal tissues), are urgently needed for the development of cancer immunotherapies. Here we report our discovery of B-cell lymphoma extra-large (BCL-XL) as a potential molecular target of tumor-infiltrating (TI) Tregs. We show that pharmacological degradation of BCL-XL using a newly developed platelet-sparing BCL-XL Proteolysis-targeting chimera (PROTAC) induces the apoptosis of TI-Tregs and the activation of TI-CD8+ T cells. Moreover, these activities result in an effective suppression of syngeneic tumor growth in immunocompetent, but not in immunodeficient or CD8+ T cell-depleted mice. Notably, treatment with BCL-XL PROTAC does not cause detectable damage within several normal tissues or thrombocytopenia. These findings identify BCL-XL as a target in the elimination of TI-Tregs as a component of cancer immunotherapies, and that the BCL-XL-specific PROTAC has the potential to be developed as a therapeutic for cancer immunotherapy.
Generation, characterization, and manipulation of quantum correlations in electron beams
Authors: Asban Shahaf , García de Abajo F. Javier 
Published: February 2021

AbstractEntanglement engineering plays a central role in quantum-enhanced technologies, with potential physical platforms that outperform their classical counterparts. However, free electrons remain largely unexplored despite their great capacity to encode and manipulate quantum information, due in part to the lack of a suitable theoretical framework. Here we link theoretical concepts from quantum information to available free-electron sources. Specifically, we consider the interactions among electrons propagating near the surface of a polariton-supporting medium and study the entanglement induced by pair-wise coupling. These correlations depend on the controlled interaction interval and the initial electron bandwidth. We show that long interaction times of broadband electrons extend their temporal coherence. This in turn is revealed through a widened Hong–Ou–Mandel peak and is associated with an increased entanglement entropy. We then introduce a discrete basis of electronic temporal modes and discriminate between them via coincidence detection with a shaped probe. This paves the way for ultrafast quantum information transfer by means of free electrons, rendering the large alphabet that they span in the time domain accessible.
Sulfur sequestration promotes multicellularity during nutrient limitation
Authors: Kelly Beth , Carrizo Gustavo E. , Edwards-Hicks Joy , Sanin David E. , Stanczak Michal A. , Priesnitz Chantal , Flachsmann Lea J. , Curtis Jonathan D. , Mittler Gerhard , Musa Yaarub , Becker Thomas , Buescher Joerg M. , Pearce Erika L. 
Published: February 2021

AbstractThe behaviour ofDictyostelium discoideumdepends on nutrients1. When sufficient food is present these amoebae exist in a unicellular state, but upon starvation they aggregate into a multicellular organism2,3. This biology makesD. discoideuman ideal model for investigating how fundamental metabolism commands cell differentiation and function. Here we show that reactive oxygen species—generated as a consequence of nutrient limitation—lead to the sequestration of cysteine in the antioxidant glutathione. This sequestration limits the use of the sulfur atom of cysteine in processes that contribute to mitochondrial metabolism and cellular proliferation, such as protein translation and the activity of enzymes that contain an iron–sulfur cluster. The regulated sequestration of sulfur maintainsD. discoideumin a nonproliferating state that paves the way for multicellular development. This mechanism of signalling through reactive oxygen species highlights oxygen and sulfur as simple signalling molecules that dictate cell fate in an early eukaryote, with implications for responses to nutrient fluctuations in multicellular eukaryotes.