bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional network constituted of CBP, Ku70, NOX2, and BAX prevents the cell death of necrosis, paraptosis, and apoptosis in human melanoma
Authors: Ding Liang , Wen Yalei , Zhang Xin , Zhao Fang , Lv Kenao , Shi Jian-hong , Shen Shigang , Pan Xuefeng 
Published: February 2021

AbstractCREB-binding protein (CBP) is an acetyltransferase known to play multiple roles in the transcriptions of genes involving oxidative metabolism, cell cycle, DNA damage checkpoints, and cell death. In this study, CBP was found to positively regulate the expression of Ku70, and both CBP and Ku70 were found to negatively regulate the expression of NOX2, therefore, mitigating the intracellular ROS in human melanoma. Knocking down CBP or Ku70 induced necrotic and paraptotic cell death as indicated by high-level intracellular ROS, cytoplasmic vacuolization, and cell cycle arrest in the S phase. In addition, chromosomal condensations were also observed in the cells proceeding necrotic and paraptotic cell death, which was found to be related to the BAX-associated intrinsic pathway of apoptotic cell death, when Ku70 was decreased either by CBP depletion or by Ku70 depletion directly. Our results, therefore, supported the idea that CBP, Ku70, BAX, and NOX2 have formed a transcriptional network in the prevention of cell death of necrosis, paraptosis, and apoptosis in human melanoma.
Cholesterol activates the Wnt/PCP-YAP signaling in SOAT1-targeted treatment of colon cancer
Authors: Xu Huanji , Xia Hongwei , Zhou Sheng , Tang Qiulin , Bi Feng 
Published: February 2021

AbstractIntracellular free cholesterol can be converted to cholesteryl ester and stored as lipid droplets through SOAT1-mediated esterification. Compelling evidence implicate targeting SOAT1 as a promising therapeutic strategy for cancer management. Herein, we demonstrate how targeting SOAT1 promotes YAP expression by elevating cellular cholesterol content in colon cancer cells. Results revealed that cholesterol alleviates the inhibitory effect of LRP6 on the Wnt/PCP pathway by impeding the interaction of LRP6 with FZD7. Subsequently, FZD7-mediated PCP signaling directly elevated YAP expression by activating RhoA. Nystatin-mediated cholesterol sequestration significantly inhibited YAP expression under SOAT1 inhibition. Moreover, nystatin synergized with the SOAT1 inhibitor avasimibe in suppressing the viability of colon cancer cells in vitro and in vivo. The present study provides new mechanistic insights into the functions of cholesterol metabolism on growth signaling pathways and implicates a novel strategy for cholesterol metabolic-targeted treatment of colon cancers.
Organic magnetoelectric and optomagnetic couplings: perspectives for organic spin optoelectronics
Authors: Wang Zhongxuan , Qin Wei 
Published: February 2021

AbstractOver the past years, the development of organic ferromagnetic materials has been investigated worldwide for potential applications. Due to the couplings among the charge, orbit, spin, and phonon in organic ferromagnetic materials, magnetoelectric, and optomagnetic couplings have been realized and observed. In this review, progress in organic magnetoelectric and optomagnetic couplings is presented, and the mechanisms behind the phenomena are also briefly summarized. Hopefully, the understanding of magnetoelectric and optomagnetic couplings could provide guidance for the further development of organic spin optoelectronics.
PlasmidHawk improves lab of origin prediction of engineered plasmids using sequence alignment
Authors: Wang Qi , Kille Bryce , Liu Tian Rui , Elworth R. A. Leo , Treangen Todd J. 
Published: February 2021

AbstractWith advances in synthetic biology and genome engineering comes a heightened awareness of potential misuse related to biosafety concerns. A recent study employed machine learning to identify the lab-of-origin of DNA sequences to help mitigate some of these concerns. Despite their promising results, this deep learning based approach had limited accuracy, was computationally expensive to train, and wasn’t able to provide the precise features that were used in its predictions. To address these shortcomings, we developed PlasmidHawk for lab-of-origin prediction. Compared to a machine learning approach, PlasmidHawk has higher prediction accuracy; PlasmidHawk can successfully predict unknown sequences’ depositing labs 76% of the time and 85% of the time the correct lab is in the top 10 candidates. In addition, PlasmidHawk can precisely single out the signature sub-sequences that are responsible for the lab-of-origin detection. In summary, PlasmidHawk represents an explainable and accurate tool for lab-of-origin prediction of synthetic plasmid sequences. PlasmidHawk is available at https://gitlab.com/treangenlab/plasmidhawk.git.
Mechanically robust amino acid crystals as fiber-optic transducers and wide bandpass filters for optical communication in the near-infrared
Authors: Karothu Durga Prasad , Dushaq Ghada , Ahmed Ejaz , Catalano Luca , Polavaram Srujana , Ferreira Rodrigo , Li Liang , Mohamed Sharmarke , Rasras Mahmoud , Naumov Panče 
Published: February 2021

AbstractOrganic crystals are emerging as mechanically compliant, light-weight and chemically versatile alternatives to the commonly used silica and polymer waveguides. However, the previously reported organic crystals were shown to be able to transmit visible light, whereas actual implementation in telecommunication devices requires transparency in the near-infrared spectral range. Here we demonstrate that single crystals of the amino acid L-threonine could be used as optical waveguides and filters with high mechanical and thermal robustness for transduction of signals in the telecommunications range. On their (00$$\bar 1$$

1

¯

) face, crystals of this material have an extraordinarily high Young’s modulus (40.95 ± 1.03 GPa) and hardness (1.98 ± 0.11 GPa) for an organic crystal. First-principles density functional theory calculations, used in conjunction with analysis of the energy frameworks to correlate the structure with the anisotropy in the Young’s modulus, showed that the high stiffness arises as a consequence of the strong charge-assisted hydrogen bonds between the zwitterions. The crystals have low optical loss in the O, E, S and C bands of the spectrum (1250−1600 nm), while they effectively block infrared light below 1200 nm. This property favors these and possibly other related organic crystals as all-organic fiber-optic waveguides and filters for transduction of information.
Direct imaging and electronic structure modulation of moiré superlattices at the 2D/3D interface
Authors: Reidy Kate , Varnavides Georgios , Thomsen Joachim Dahl , Kumar Abinash , Pham Thang , Blackburn Arthur M. , Anikeeva Polina , Narang Prineha , LeBeau James M. , Ross Frances M. 
Published: February 2021

AbstractThe atomic structure at the interface between two-dimensional (2D) and three-dimensional (3D) materials influences properties such as contact resistance, photo-response, and high-frequency electrical performance. Moiré engineering is yet to be utilized for tailoring this 2D/3D interface, despite its success in enabling correlated physics at 2D/2D interfaces. Using epitaxially aligned MoS2/Au{111} as a model system, we demonstrate the use of advanced scanning transmission electron microscopy (STEM) combined with a geometric convolution technique in imaging the crystallographic 32 Å moiré pattern at the 2D/3D interface. This moiré period is often hidden in conventional electron microscopy, where the Au structure is seen in projection. We show, via ab initio electronic structure calculations, that charge density is modulated according to the moiré period, illustrating the potential for (opto-)electronic moiré engineering at the 2D/3D interface. Our work presents a general pathway to directly image periodic modulation at interfaces using this combination of emerging microscopy techniques.
Picosecond time-resolved photon antibunching measures nanoscale exciton motion and the true number of chromophores
Authors: Hedley Gordon J. , Schröder Tim , Steiner Florian , Eder Theresa , Hofmann Felix J. , Bange Sebastian , Laux Dirk , Höger Sigurd , Tinnefeld Philip , Lupton John M. , Vogelsang Jan 
Published: February 2021

AbstractThe particle-like nature of light becomes evident in the photon statistics of fluorescence from single quantum systems as photon antibunching. In multichromophoric systems, exciton diffusion and subsequent annihilation occurs. These processes also yield photon antibunching but cannot be interpreted reliably. Here we develop picosecond time-resolved antibunching to identify and decode such processes. We use this method to measure the true number of chromophores on well-defined multichromophoric DNA-origami structures, and precisely determine the distance-dependent rates of annihilation between excitons. Further, this allows us to measure exciton diffusion in mesoscopic H- and J-type conjugated-polymer aggregates. We distinguish between one-dimensional intra-chain and three-dimensional inter-chain exciton diffusion at different times after excitation and determine the disorder-dependent diffusion lengths. Our method provides a powerful lens through which excitons can be studied at the single-particle level, enabling the rational design of improved excitonic probes such as ultra-bright fluorescent nanoparticles and materials for optoelectronic devices.
Machine learning in spectral domain
Authors: Giambagli Lorenzo , Buffoni Lorenzo , Carletti Timoteo , Nocentini Walter , Fanelli Duccio 
Published: February 2021

AbstractDeep neural networks are usually trained in the space of the nodes, by adjusting the weights of existing links via suitable optimization protocols. We here propose a radically new approach which anchors the learning process to reciprocal space. Specifically, the training acts on the spectral domain and seeks to modify the eigenvalues and eigenvectors of transfer operators in direct space. The proposed method is ductile and can be tailored to return either linear or non-linear classifiers. Adjusting the eigenvalues, when freezing the eigenvectors entries, yields performances that are superior to those attained with standard methods restricted to operate with an identical number of free parameters. To recover a feed-forward architecture in direct space, we have postulated a nested indentation of the eigenvectors. Different non-orthogonal basis could be employed to export the spectral learning to other frameworks, as e.g. reservoir computing.
Marine furanocembranoids-inspired macrocycles enabled by Pd-catalyzed unactivated C(sp3)-H olefination mediated by donor/donor carbenes
Authors: Hao Jiping , Guo Xueying , He Shijun , Xu Zhongliang , Chen Lu , Li Zhongyu , Song Bichao , Zuo Jianping , Lin Zhenyang , Yang Weibo 
Published: February 2021

AbstractBiomimetic modularization and function-oriented synthesis of structurally diversified natural product-like macrocycles in a step-economical fashion is highly desirable. Inspired by marine furanocembranoids, herein, we synthesize diverse alkenes substituted furan-embedded macrolactams via a modular biomimetic assembly strategy. The success of this assembly is the development of crucial Pd-catalyzed carbene coupling between ene-yne-ketones as donor/donor carbene precursors and unactivated Csp3‒H bonds which represents a great challenge in organic synthesis. Notably, this method not only obviates the use of unstable, explosive, and toxic diazo compounds, but also can be amenable to allenyl ketones carbene precursors. DFT calculations demonstrate that a formal 1,4-Pd shift could be involved in the mechanism. Moreover, the collected furanocembranoids-like macrolactams show significant anti-inflammatory activities against TNF-α, IL-6, and IL-1β and the cytotoxicity is comparable to Dexamethasone.
Mechanochemical control of epidermal stem cell divisions by B-plexins
Authors: Jiang Chen , Javed Ahsan , Kaiser Laura , Nava Michele M. , Xu Rui , Brandt Dominique T. , Zhao Dandan , Mayer Benjamin , Fernández-Baldovinos Javier , Zhou Luping , Höß Carsten , Sawmynaden Kovilen , Oleksy Arkadiusz , Matthews David , Weinstein Lee S. , Hahn Heidi , Gröne Hermann-Josef , Graumann Peter L. , Niessen Carien M. , Offermanns Stefan , Wickström Sara A. , Worzfeld Thomas 
Published: February 2021

AbstractThe precise spatiotemporal control of cell proliferation is key to the morphogenesis of epithelial tissues. Epithelial cell divisions lead to tissue crowding and local changes in force distribution, which in turn suppress the rate of cell divisions. However, the molecular mechanisms underlying this mechanical feedback are largely unclear. Here, we identify a critical requirement of B-plexin transmembrane receptors in the response to crowding-induced mechanical forces during embryonic skin development. Epidermal stem cells lacking B-plexins fail to sense mechanical compression, resulting in disinhibition of the transcriptional coactivator YAP, hyperproliferation, and tissue overgrowth. Mechanistically, we show that B-plexins mediate mechanoresponses to crowding through stabilization of adhesive cell junctions and lowering of cortical stiffness. Finally, we provide evidence that the B-plexin-dependent mechanochemical feedback is also pathophysiologically relevant to limit tumor growth in basal cell carcinoma, the most common type of skin cancer. Our data define a central role of B-plexins in mechanosensation to couple cell density and cell division in development and disease.
A CSB-PAF1C axis restores processive transcription elongation after DNA damage repair
Authors: van den Heuvel Diana , Spruijt Cornelia G. , González-Prieto Román , Kragten Angela , Paulsen Michelle T. , Zhou Di , Wu Haoyu , Apelt Katja , van der Weegen Yana , Yang Kevin , Dijk Madelon , Daxinger Lucia , Marteijn Jurgen A. , Vertegaal Alfred C. O. , Ljungman Mats , Vermeulen Michiel , Luijsterburg Martijn S. 
Published: February 2021

AbstractBulky DNA lesions in transcribed strands block RNA polymerase II (RNAPII) elongation and induce a genome-wide transcriptional arrest. The transcription-coupled repair (TCR) pathway efficiently removes transcription-blocking DNA lesions, but how transcription is restored in the genome following DNA repair remains unresolved. Here, we find that the TCR-specific CSB protein loads the PAF1 complex (PAF1C) onto RNAPII in promoter-proximal regions in response to DNA damage. Although dispensable for TCR-mediated repair, PAF1C is essential for transcription recovery after UV irradiation. We find that PAF1C promotes RNAPII pause release in promoter-proximal regions and subsequently acts as a processivity factor that stimulates transcription elongation throughout genes. Our findings expose the molecular basis for a non-canonical PAF1C-dependent pathway that restores transcription throughout the human genome after genotoxic stress.
Quasi-one-dimensional metallic conduction channels in exotic ferroelectric topological defects
Authors: Yang Wenda , Tian Guo , Zhang Yang , Xue Fei , Zheng Dongfeng , Zhang Luyong , Wang Yadong , Chen Chao , Fan Zhen , Hou Zhipeng , Chen Deyang , Gao Jinwei , Zeng Min , Qin Minghui , Chen Long-Qing , Gao Xingsen , Liu Jun-Ming 
Published: February 2021

AbstractFerroelectric topological objects provide a fertile ground for exploring emerging physical properties that could potentially be utilized in future nanoelectronic devices. Here, we demonstrate quasi-one-dimensional metallic high conduction channels associated with the topological cores of quadrant vortex domain and center domain (monopole-like) states confined in high quality BiFeO3 nanoislands, abbreviated as the vortex core and the center core. We unveil via the phase-field simulation that the superfine metallic conduction channels along the center cores arise from the screening charge carriers confined at the core region, whereas the high conductance of vortex cores results from a field-induced twisted state. These conducting channels can be reversibly created and deleted by manipulating the two topological states via electric field, leading to an apparent electroresistance effect with an on/off ratio higher than 103. These results open up the possibility of utilizing these functional one-dimensional topological objects in high-density nanoelectronic devices, e.g. nonvolatile memory.
Pre-mitotic genome re-organisation bookends the B cell differentiation process
Authors: Chan Wing Fuk , Coughlan Hannah D. , Zhou Jie H. S. , Keenan Christine R. , Bediaga Naiara G. , Hodgkin Philip D. , Smyth Gordon K. , Johanson Timothy M. , Allan Rhys S. 
Published: February 2021

AbstractDuring cellular differentiation chromosome conformation is intricately remodelled to support the lineage-specific transcriptional programs required for initiating and maintaining lineage identity. When these changes occur in relation to cell cycle, division and time in response to cellular activation and differentiation signals has yet to be explored, although it has been proposed to occur during DNA synthesis or after mitosis. Here, we elucidate the chromosome conformational changes in B lymphocytes as they differentiate and expand from a naive, quiescent state into antibody secreting plasma cells. We find gene-regulatory chromosome reorganization in late G1 phase before the first division, and that this configuration is remarkably stable as the cells massively and rapidly clonally expand. A second wave of conformational change occurs as cells terminally differentiate into plasma cells, coincident with increased time in G1 phase. These results provide further explanation for how lymphocyte fate is imprinted prior to the first division. They also suggest that chromosome reconfiguration occurs prior to DNA replication and mitosis, and is linked to a gene expression program that controls the differentiation process required for the generation of immunity.
System-wide identification and prioritization of enzyme substrates by thermal analysis
Authors: Saei Amir Ata , Beusch Christian M. , Sabatier Pierre , Wells Juan Astorga , Gharibi Hassan , Meng Zhaowei , Chernobrovkin Alexey , Rodin Sergey , Näreoja Katja , Thorsell Ann-Gerd , Karlberg Tobias , Cheng Qing , Lundström Susanna L. , Gaetani Massimiliano , Végvári Ákos , Arnér Elias S. J. , Schüler Herwig , Zubarev Roman A. 
Published: February 2021

AbstractDespite the immense importance of enzyme–substrate reactions, there is a lack of general and unbiased tools for identifying and prioritizing substrate proteins that are modified by the enzyme on the structural level. Here we describe a high-throughput unbiased proteomics method called System-wide Identification and prioritization of Enzyme Substrates by Thermal Analysis (SIESTA). The approach assumes that the enzymatic post-translational modification of substrate proteins is likely to change their thermal stability. In our proof-of-concept studies, SIESTA successfully identifies several known and novel substrate candidates for selenoprotein thioredoxin reductase 1, protein kinase B (AKT1) and poly-(ADP-ribose) polymerase-10 systems. Wider application of SIESTA can enhance our understanding of the role of enzymes in homeostasis and disease, opening opportunities to investigate the effect of post-translational modifications on signal transduction and facilitate drug discovery.
Blastocyst complementation using Prdm14-deficient rats enables efficient germline transmission and generation of functional mouse spermatids in rats
Authors: Kobayashi Toshihiro , Goto Teppei , Oikawa Mami , Sanbo Makoto , Yoshida Fumika , Terada Reiko , Niizeki Naoko , Kajitani Naoyo , Kazuki Kanako , Kazuki Yasuhiro , Hochi Shinichi , Nakauchi Hiromitsu , Surani M. Azim , Hirabayashi Masumi 
Published: February 2021

AbstractMurine animal models from genetically modified pluripotent stem cells (PSCs) are essential for functional genomics and biomedical research, which require germline transmission for the establishment of colonies. However, the quality of PSCs, and donor-host cell competition in chimeras often present strong barriers for germline transmission. Here, we report efficient germline transmission of recalcitrant PSCs via blastocyst complementation, a method to compensate for missing tissues or organs in genetically modified animals via blastocyst injection of PSCs. We show that blastocysts from germline-deficient Prdm14 knockout rats provide a niche for the development of gametes originating entirely from the donor PSCs without any detriment to somatic development. We demonstrate the potential of this approach by creating PSC-derived Pax2/Pax8 double mutant anephric rats, and rescuing germline transmission of a PSC carrying a mouse artificial chromosome. Furthermore, we generate mouse PSC-derived functional spermatids in rats, which provides a proof-of-principle for the generation of xenogenic gametes in vivo. We believe this approach will become a useful system for generating PSC-derived germ cells in the future.
Electromechanically reconfigurable optical nano-kirigami
Authors: Chen Shanshan , Liu Zhiguang , Du Huifeng , Tang Chengchun , Ji Chang-Yin , Quan Baogang , Pan Ruhao , Yang Lechen , Li Xinhao , Gu Changzhi , Zhang Xiangdong , Yao Yugui , Li Junjie , Fang Nicholas X. , Li Jiafang 
Published: February 2021

AbstractKirigami, with facile and automated fashion of three-dimensional (3D) transformations, offers an unconventional approach for realizing cutting-edge optical nano-electromechanical systems. Here, we demonstrate an on-chip and electromechanically reconfigurable nano-kirigami with optical functionalities. The nano-electromechanical system is built on an Au/SiO2/Si substrate and operated via attractive electrostatic forces between the top gold nanostructure and bottom silicon substrate. Large-range nano-kirigami like 3D deformations are clearly observed and reversibly engineered, with scalable pitch size down to 0.975 μm. Broadband nonresonant and narrowband resonant optical reconfigurations are achieved at visible and near-infrared wavelengths, respectively, with a high modulation contrast up to 494%. On-chip modulation of optical helicity is further demonstrated in submicron nano-kirigami at near-infrared wavelengths. Such small-size and high-contrast reconfigurable optical nano-kirigami provides advanced methodologies and platforms for versatile on-chip manipulation of light at nanoscale.
Structure-guided insights into heterocyclic ring-cleavage catalysis of the non-heme Fe (II) dioxygenase NicX
Authors: Liu Gongquan , Zhao Yi-Lei , He Fangyuan , Zhang Peng , Ouyang Xingyu , Tang Hongzhi , Xu Ping 
Published: February 2021

AbstractBiodegradation of aromatic and heterocyclic compounds requires an oxidative ring cleavage enzymatic step. Extensive biochemical research has yielded mechanistic insights about catabolism of aromatic substrates; yet much less is known about the reaction mechanisms underlying the cleavage of heterocyclic compounds such as pyridine-ring-containing ones like 2,5-hydroxy-pyridine (DHP). 2,5-Dihydroxypyridine dioxygenase (NicX) from Pseudomonas putida KT2440 uses a mononuclear nonheme Fe(II) to catalyze the oxidative pyridine ring cleavage reaction by transforming DHP into N-formylmaleamic acid (NFM). Herein, we report a crystal structure for the resting form of NicX, as well as a complex structure wherein DHP and NFM are trapped in different subunits. The resting state structure displays an octahedral coordination for Fe(II) with two histidine residues (His265 and His318), a serine residue (Ser302), a carboxylate ligand (Asp320), and two water molecules. DHP does not bind as a ligand to Fe(II), yet its interactions with Leu104 and His105 function to guide and stabilize the substrate to the appropriate position to initiate the reaction. Additionally, combined structural and computational analyses lend support to an apical dioxygen catalytic mechanism. Our study thus deepens understanding of non-heme Fe(II) dioxygenases.