bluuebunny/crossref_metadata_2025_split huggingface dataset:
MdVQ37 overexpression reduces basal thermotolerance in transgenic apple by affecting transcription factor activity and salicylic acid homeostasis
Authors: Dong Qinglong , Duan Dingyue , Zheng Wenqian , Huang Dong , Wang Qian , Li Xiaoran , Mao Ke , Ma Fengwang 
Published: October 2021

AbstractHigh temperature (HT) is one of the most important environmental stress factors and seriously threatens plant growth, development, and production. VQ motif-containing proteins are transcriptional regulators that have been reported to regulate plant growth and developmental processes, including responses to biotic and abiotic stresses. However, the relationships between VQ motif-containing proteins and HT stress have not been studied in depth in plants. In this study, transgenic apple (Malus domestica) plants overexpressing the apple VQ motif-containing protein-coding gene (MdVQ37) were exposed to HT stress, and the transgenic lines exhibited a heat-sensitive phenotype. In addition, physiological and biochemical studies revealed that, compared with WT plants, transgenic lines had lower enzymatic activity and photosynthetic capacity and lower amounts of nonenzymatic antioxidant system metabolites under HT stress. Transcriptome analysis revealed 1379 genes whose expression differed between the transgenic lines and WT plants. GO and KEGG pathway analyses showed that transcription factor activity and plant hormone signaling pathways were differentially influenced and enriched in the transgenic lines. Salicylic acid (SA) content analysis indicated that overexpression of MdVQ37 reduced the content of endogenous SA by regulating the expression of SA catabolism-related genes, which ultimately resulted in disruption of the SA-dependent signaling pathway under HT stress. The application of SA slightly increased the survival rate of the transgenic lines under HT stress. Taken together, our results indicate that apple MdVQ37 has a regulatory function in basal thermotolerance by modulating the activity of transcription factors and SA homeostasis. Overall, this study provides novel insights that improve our understanding of the various functions of VQ motif-containing proteins.
Standardized preservation, extraction and quantification techniques for detection of fecal SARS-CoV-2 RNA
Authors: Natarajan Aravind , Han Alvin , Zlitni Soumaya , Brooks Erin F. , Vance Summer E. , Wolfe Marlene , Singh Upinder , Jagannathan Prasanna , Pinsky Benjamin A. , Boehm Alexandria , Bhatt Ami S. 
Published: October 2021

AbstractPatients with COVID-19 shed SARS-CoV-2 RNA in stool, sometimes well after their respiratory infection has cleared. This may be significant for patient health, epidemiology, and diagnosis. However, methods to preserve stool, and to extract and quantify viral RNA are not standardized. We test the performance of three preservative approaches at yielding detectable SARS-CoV-2 RNA: the OMNIgene-GUT kit, Zymo DNA/RNA shield kit, and the most commonly applied, storage without preservative. We test these in combination with three extraction kits: QIAamp Viral RNA Mini Kit, Zymo Quick-RNA Viral Kit, and MagMAX Viral/Pathogen Kit. We also test the utility of ddPCR and RT-qPCR for the reliable quantification of SARS-CoV-2 RNA from stool. We identify that the Zymo DNA/RNA preservative and the QiaAMP extraction kit yield more detectable RNA than the others, using both ddPCR and RT-qPCR. Taken together, we recommend a comprehensive methodology for preservation, extraction and detection of RNA from SARS-CoV-2 and other coronaviruses in stool.
A rational blueprint for the design of chemically-controlled protein switches
Authors: Shui Sailan , Gainza Pablo , Scheller Leo , Yang Che , Kurumida Yoichi , Rosset Stéphane , Georgeon Sandrine , Di Roberto Raphaël B. , Castellanos-Rueda Rocío , Reddy Sai T. , Correia Bruno E. 
Published: October 2021

AbstractSmall-molecule responsive protein switches are crucial components to control synthetic cellular activities. However, the repertoire of small-molecule protein switches is insufficient for many applications, including those in the translational spaces, where properties such as safety, immunogenicity, drug half-life, and drug side-effects are critical. Here, we present a computational protein design strategy to repurpose drug-inhibited protein-protein interactions as OFF- and ON-switches. The designed binders and drug-receptors form chemically-disruptable heterodimers (CDH) which dissociate in the presence of small molecules. To design ON-switches, we converted the CDHs into a multi-domain architecture which we refer to as activation by inhibitor release switches (AIR) that incorporate a rationally designed drug-insensitive receptor protein. CDHs and AIRs showed excellent performance as drug responsive switches to control combinations of synthetic circuits in mammalian cells. This approach effectively expands the chemical space and logic responses in living cells and provides a blueprint to develop new ON- and OFF-switches.
Complex small-world regulatory networks emerge from the 3D organisation of the human genome
Authors: Brackley C. A. , Gilbert N. , Michieletto D. , Papantonis A. , Pereira M. C. F. , Cook P. R. , Marenduzzo D. 
Published: October 2021

AbstractThe discovery that overexpressing one or a few critical transcription factors can switch cell state suggests that gene regulatory networks are relatively simple. In contrast, genome-wide association studies (GWAS) point to complex phenotypes being determined by hundreds of loci that rarely encode transcription factors and which individually have small effects. Here, we use computer simulations and a simple fitting-free polymer model of chromosomes to show that spatial correlations arising from 3D genome organisation naturally lead to stochastic and bursty transcription as well as complex small-world regulatory networks (where the transcriptional activity of each genomic region subtly affects almost all others). These effects require factors to be present at sub-saturating levels; increasing levels dramatically simplifies networks as more transcription units are pressed into use. Consequently, results from GWAS can be reconciled with those involving overexpression. We apply this pan-genomic model to predict patterns of transcriptional activity in whole human chromosomes, and, as an example, the effects of the deletion causing the diGeorge syndrome.
Growth and site-specific organization of micron-scale biomolecular devices on living mammalian cells
Authors: Jia Sisi , Phua Siew Cheng , Nihongaki Yuta , Li Yizeng , Pacella Michael , Li Yi , Mohammed Abdul M. , Sun Sean , Inoue Takanari , Schulman Rebecca 
Published: September 2021

AbstractMesoscale molecular assemblies on the cell surface, such as cilia and filopodia, integrate information, control transport and amplify signals. Designer cell-surface assemblies could control these cellular functions. Such assemblies could be constructed from synthetic components ex vivo, making it possible to form such structures using modern nanoscale self-assembly and fabrication techniques, and then oriented on the cell surface. Here we integrate synthetic devices, micron-scale DNA nanotubes, with mammalian cells by anchoring them by their ends to specific cell surface receptors. These filaments can measure shear stresses between 0-2 dyn/cm2, a regime important for cell signaling. Nanotubes can also grow while anchored to cells, thus acting as dynamic cell components. This approach to cell surface engineering, in which synthetic biomolecular assemblies are organized with existing cellular architecture, could make it possible to build new types of sensors, machines and scaffolds that can interface with, control and measure properties of cells.
Entropic singularities give rise to quantum transmission
Authors: Siddhu Vikesh 
Published: October 2021

AbstractWhen can noiseless quantum information be sent across noisy quantum devices? And at what maximum rate? These questions lie at the heart of quantum technology, but remain unanswered because of non-additivity— a fundamental synergy which allows quantum devices (aka quantum channels) to send more information than expected. Previously, non-additivity was known to occur in very noisy channels with coherent information much smaller than that of a perfect channel; but, our work shows non-additivity in a simple low-noise channel. Our results extend even further. We prove a general theorem concerning positivity of a channel’s coherent information. A corollary of this theorem gives a simple dimensional test for a channel’s capacity. Applying this corollary solves an open problem by characterizing all qubit channels whose complement has non-zero capacity. Another application shows a wide class of zero quantum capacity qubit channels can assist an incomplete erasure channel in sending quantum information. These results arise from introducing and linking logarithmic singularities in the von-Neumann entropy with quantum transmission: changes in entropy caused by this singularity are a mechanism responsible for both positivity and non-additivity of the coherent information. Analysis of such singularities may be useful in other physics problems.
ECNet is an evolutionary context-integrated deep learning framework for protein engineering
Authors: Luo Yunan , Jiang Guangde , Yu Tianhao , Liu Yang , Vo Lam , Ding Hantian , Su Yufeng , Qian Wesley Wei , Zhao Huimin , Peng Jian 
Published: September 2021

AbstractMachine learning has been increasingly used for protein engineering. However, because the general sequence contexts they capture are not specific to the protein being engineered, the accuracy of existing machine learning algorithms is rather limited. Here, we report ECNet (evolutionary context-integrated neural network), a deep-learning algorithm that exploits evolutionary contexts to predict functional fitness for protein engineering. This algorithm integrates local evolutionary context from homologous sequences that explicitly model residue-residue epistasis for the protein of interest with the global evolutionary context that encodes rich semantic and structural features from the enormous protein sequence universe. As such, it enables accurate mapping from sequence to function and provides generalization from low-order mutants to higher-order mutants. We show that ECNet predicts the sequence-function relationship more accurately as compared to existing machine learning algorithms by using ~50 deep mutational scanning and random mutagenesis datasets. Moreover, we used ECNet to guide the engineering of TEM-1 β-lactamase and identified variants with improved ampicillin resistance with high success rates.
Efficient propyne/propadiene separation by microporous crystalline physiadsorbents
Authors: Peng Yun-Lei , Wang Ting , Jin Chaonan , Deng Cheng-Hua , Zhao Yanming , Liu Wansheng , Forrest Katherine A. , Krishna Rajamani , Chen Yao , Pham Tony , Space Brian , Cheng Peng , Zaworotko Michael J. , Zhang Zhenjie 
Published: October 2021

AbstractSelective separation of propyne/propadiene mixture to obtain pure propadiene (allene), an essential feedstock for organic synthesis, remains an unsolved challenge in the petrochemical industry, thanks mainly to their similar physicochemical properties. We herein introduce a convenient and energy-efficient physisorptive approach to achieve propyne/propadiene separation using microporous metal-organic frameworks (MOFs). Specifically, HKUST-1, one of the most widely studied high surface area MOFs that is available commercially, is found to exhibit benchmark performance (propadiene production up to 69.6 cm3/g, purity > 99.5%) as verified by dynamic breakthrough experiments. Experimental and modeling studies provide insight into the performance of HKUST-1 and indicate that it can be attributed to a synergy between thermodynamics and kinetics that arises from abundant open metal sites and cage-based molecular traps in HKUST-1.
Pentaphosphaferrocene-mediated synthesis of asymmetric organo-phosphines starting from white phosphorus
Authors: Reichl Stephan , Mädl Eric , Riedlberger Felix , Piesch Martin , Balázs Gábor , Seidl Michael , Scheer Manfred 
Published: October 2021

AbstractThe synthesis of phosphines is based on white phosphorus, which is usually converted to PCl3, to be afterwards substituted step by step in a non-atomic efficient manner. Herein, we describe an alternative efficient transition metal-mediated process to form asymmetrically substituted phosphines directly from white phosphorus (P4). Thereby, P4is converted to [Cp*Fe(η5-P5)] (1) (Cp* = η5-C5(CH3)5) in which one of the phosphorus atoms is selectively functionalized to the 1,1-diorgano-substituted complex [Cp*Fe(η4-P5R′R″)] (3). In a subsequent step, the phosphine PR′R″R‴ (R′ ≠ R″ ≠ R‴ = alky, aryl) (4) is released by reacting it with a nucleophile R‴M (M = alkali metal) as racemates. The starting material1can be regenerated with P4and can be reused in multiple reaction cycles without isolation of the intermediates, and only the phosphine is distilled off.
Boson-peak-like anomaly caused by transverse phonon softening in strain glass
Authors: Ren Shuai , Zong Hong-Xiang , Tao Xue-Fei , Sun Yong-Hao , Sun Bao-An , Xue De-Zhen , Ding Xiang-Dong , Wang Wei-Hua 
Published: October 2021

AbstractStrain glass is a glassy state with frozen ferroelastic/martensitic nanodomains in shape memory alloys, yet its nature remains unclear. Here, we report a glassy feature in strain glass that was thought to be only present in structural glasses. An abnormal hump is observed in strain glass around 10 K upon normalizing the specific heat by cubed temperature, similar to the boson peak in metallic glass. The simulation studies show that this boson-peak-like anomaly is caused by the phonon softening of the non-transforming matrix surrounding martensitic domains, which occurs in a transverse acoustic branch not associated with the martensitic transformation displacements. Therefore, this anomaly neither is a relic of van Hove singularity nor can be explained by other theories relying on structural disorder, while it verifies a recent theoretical model without any assumptions of disorder. This work might provide fresh insights in understanding the nature of glassy states and associated vibrational properties.
Subtype heterogeneity and epigenetic convergence in neuroendocrine prostate cancer
Authors: Cejas Paloma , Xie Yingtian , Font-Tello Alba , Lim Klothilda , Syamala Sudeepa , Qiu Xintao , Tewari Alok K. , Shah Neel , Nguyen Holly M. , Patel Radhika A. , Brown Lisha , Coleman Ilsa , Hackeng Wenzel M. , Brosens Lodewijk , Dreijerink Koen M. A. , Ellis Leigh , Alaiwi Sarah Abou , Seo Ji-Heui , Baca Sylvan , Beltran Himisha , Khani Francesca , Pomerantz Mark , Dall’Agnese Alessandra , Crowdis Jett , Van Allen Eliezer M. , Bellmunt Joaquim , Morrisey Colm , Nelson Peter S. , DeCaprio James , Farago Anna , Dyson Nicholas , Drapkin Benjamin , Liu X. Shirley , Freedman Matthew , Haffner Michael C. , Corey Eva , Brown Myles , Long Henry W. 
Published: October 2021

AbstractNeuroendocrine carcinomas (NEC) are tumors expressing markers of neuronal differentiation that can arise at different anatomic sites but have strong histological and clinical similarities. Here we report the chromatin landscapes of a range of human NECs and show convergence to the activation of a common epigenetic program. With a particular focus on treatment emergent neuroendocrine prostate cancer (NEPC), we analyze cell lines, patient-derived xenograft (PDX) models and human clinical samples to show the existence of two distinct NEPC subtypes based on the expression of the neuronal transcription factors ASCL1 and NEUROD1. While in cell lines and PDX models these subtypes are mutually exclusive, single-cell analysis of human clinical samples exhibits a more complex tumor structure with subtypes coexisting as separate sub-populations within the same tumor. These tumor sub-populations differ genetically and epigenetically contributing to intra- and inter-tumoral heterogeneity in human metastases. Overall, our results provide a deeper understanding of the shared clinicopathological characteristics shown by NECs. Furthermore, the intratumoral heterogeneity of human NEPCs suggests the requirement of simultaneous targeting of coexisting tumor populations as a therapeutic strategy.
SPOP mutation induces replication over-firing by impairing Geminin ubiquitination and triggers replication catastrophe upon ATR inhibition
Authors: Ma Jian , Shi Qing , Cui Gaofeng , Sheng Haoyue , Botuyan Maria Victoria , Zhou Yingke , Yan Yuqian , He Yundong , Wang Liguo , Wang Yuzhuo , Mer Georges , Ye Dingwei , Wang Chenji , Huang Haojie 
Published: October 2021

AbstractGeminin and its binding partner Cdt1 are essential for the regulation of DNA replication. Here we show that the CULLIN3 E3 ubiquitin ligase adaptor protein SPOP binds Geminin at endogenous level and regulates DNA replication. SPOP promotes K27-linked non-degradative poly-ubiquitination of Geminin at lysine residues 100 and 127. This poly-ubiquitination of Geminin prevents DNA replication over-firing by indirectly blocking the association of Cdt1 with the MCM protein complex, an interaction required for DNA unwinding and replication. SPOP is frequently mutated in certain human cancer types and implicated in tumorigenesis. We show that cancer-associated SPOP mutations impair Geminin K27-linked poly-ubiquitination and induce replication origin over-firing and re-replication. The replication stress caused by SPOP mutations triggers replication catastrophe and cell death upon ATR inhibition. Our results reveal a tumor suppressor role of SPOP in preventing DNA replication over-firing and genome instability and suggest that SPOP-mutated tumors may be susceptible to ATR inhibitor therapy.
Ring finger protein 213 assembles into a sensor for ISGylated proteins with antimicrobial activity
Authors: Thery Fabien , Martina Lia , Asselman Caroline , Zhang Yifeng , Vessely Madeleine , Repo Heidi , Sedeyn Koen , Moschonas George D. , Bredow Clara , Teo Qi Wen , Zhang Jingshu , Leandro Kevin , Eggermont Denzel , De Sutter Delphine , Boucher Katie , Hochepied Tino , Festjens Nele , Callewaert Nico , Saelens Xavier , Dermaut Bart , Knobeloch Klaus-Peter , Beling Antje , Sanyal Sumana , Radoshevich Lilliana , Eyckerman Sven , Impens Francis 
Published: October 2021

AbstractISG15 is an interferon-stimulated, ubiquitin-like protein that can conjugate to substrate proteins (ISGylation) to counteract microbial infection, but the underlying mechanisms remain elusive. Here, we use a virus-like particle trapping technology to identify ISG15-binding proteins and discover Ring Finger Protein 213 (RNF213) as an ISG15 interactor and cellular sensor of ISGylated proteins. RNF213 is a poorly characterized, interferon-induced megaprotein that is frequently mutated in Moyamoya disease, a rare cerebrovascular disorder. We report that interferon induces ISGylation and oligomerization of RNF213 on lipid droplets, where it acts as a sensor for ISGylated proteins. We show that RNF213 has broad antimicrobial activity in vitro and in vivo, counteracting infection withListeria monocytogenes, herpes simplex virus 1, human respiratory syncytial virus and coxsackievirus B3, and we observe a striking co-localization of RNF213 with intracellular bacteria. Together, our findings provide molecular insights into the ISGylation pathway and reveal RNF213 as a key antimicrobial effector.
Rett syndrome linked to defects in forming the MeCP2/Rbfox/LASR complex in mouse models
Authors: Jiang Yan , Fu Xing , Zhang Yuhan , Wang Shen-Fei , Zhu Hong , Wang Wei-Kang , Zhang Lin , Wu Ping , Wong Catherine C. L. , Li Jinsong , Ma Jinbiao , Guan Ji-Song , Huang Ying , Hui Jingyi 
Published: October 2021

AbstractRett syndrome (RTT) is a severe neurological disorder and a leading cause of intellectual disability in young females. RTT is mainly caused by mutations found in the X-linked gene encoding methyl-CpG binding protein 2 (MeCP2). Despite extensive studies, the molecular mechanism underlying RTT pathogenesis is still poorly understood. Here, we report MeCP2 as a key subunit of a higher-order multiunit protein complex Rbfox/LASR. Defective MeCP2 in RTT mouse models disrupts the assembly of the MeCP2/Rbfox/LASR complex, leading to reduced binding of Rbfox proteins to target pre-mRNAs and aberrant splicing of Nrxns and Nlgn1 critical for synaptic plasticity. We further show that MeCP2 disease mutants display defective condensate properties and fail to promote phase-separated condensates with Rbfox proteins in vitro and in cultured cells. These data link an impaired function of MeCP2 with disease mutation in splicing control to its defective properties in mediating the higher-order assembly of the MeCP2/Rbfox/LASR complex.
Experimental study of quantum coherence decomposition and trade-off relations in a tripartite system
Authors: Ding Zhe , Liu Ran , Radhakrishnan Chandrashekar , Ma Wenchao , Peng Xinhua , Wang Ya , Byrnes Tim , Shi Fazhan , Du Jiangfeng 
Published: October 2021

AbstractQuantum coherence is the most fundamental of all quantum quantifiers, underlying other well-known quantities such as entanglement. It can be distributed in a multipartite system in various ways—for example, in a bipartite system it can exist within subsystems (local coherence) or collectively between the subsystems (global coherence), and exhibits a trade-off relation. In this paper, we experimentally verify these coherence trade-off relations in adiabatically evolved nuclear spin systems using an NMR spectrometer. We study the full set of coherence trade-off relations between the original state, the bipartite product state, the tripartite product state, and the decohered product state. We also experimentally verify the monogamy inequality and show that both the quantum systems are polygamous during the evolution. We find that the properties of the state in terms of coherence and monogamy are equivalent. This illustrates the utility of using coherence as a characterization tool for quantum states.
Terahertz signatures of ultrafast Dirac fermion relaxation at the surface of topological insulators
Authors: Kovalev S. , Tielrooij K.-J. , Deinert J.-C. , Ilyakov I. , Awari N. , Chen M. , Ponomaryov A. , Bawatna M. , de Oliveira T. V. A. G. , Eng L. M. , Kuznetsov K. A. , Safronenkov D. A. , Kitaeva G. Kh. , Kuznetsov P. I. , Hafez H. A. , Turchinovich D. , Gensch M. 
Published: October 2021

AbstractTopologically protected surface states present rich physics and promising spintronic, optoelectronic, and photonic applications that require a proper understanding of their ultrafast carrier dynamics. Here, we investigate these dynamics in topological insulators (TIs) of the bismuth and antimony chalcogenide family, where we isolate the response of Dirac fermions at the surface from the response of bulk carriers by combining photoexcitation with below-bandgap terahertz (THz) photons and TI samples with varying Fermi level, including one sample with the Fermi level located within the bandgap. We identify distinctly faster relaxation of charge carriers in the topologically protected Dirac surface states (few hundred femtoseconds), compared to bulk carriers (few picoseconds). In agreement with such fast cooling dynamics, we observe THz harmonic generation without any saturation effects for increasing incident fields, unlike graphene which exhibits strong saturation. This opens up promising avenues for increased THz nonlinear conversion efficiencies, and high-bandwidth optoelectronic and spintronic information and communication applications.