bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutual dependency between lncRNA LETN and protein NPM1 in controlling the nucleolar structure and functions sustaining cell proliferation
Authors: Wang Xianteng , Hu Xiaolin , Song Wanlu , Xu Hui , Xiao Zhengtao , Huang Rongyao , Bai Qingran , Zhang Fan , Chen Yongzhen , Liu Yu , Fang Jianhuo , Li Xin , Shen Qin , Zhao Haitao , Yang Xuerui 
Published: January 2021

AbstractFundamental processes such as ribosomal RNA synthesis and chromatin remodeling take place in the nucleolus, which is hyperactive in fast-proliferating cells. The sophisticated regulatory mechanism underlying the dynamic nucleolar structure and functions is yet to be fully explored. The present study uncovers the mutual functional dependency between a previously uncharacterized human long non-coding RNA, which we renamed LETN, and a key nucleolar protein, NPM1. Specifically, being upregulated in multiple types of cancer, LETN resides in the nucleolus via direct binding with NPM1. LETN plays a critical role in facilitating the formation of NPM1 pentamers, which are essential building blocks of the nucleolar granular component and control the nucleolar functions. Repression of LETN or NPM1 led to similar and profound changes of the nucleolar morphology and arrest of the nucleolar functions, which led to proliferation inhibition of human cancer cells and neural progenitor cells. Interestingly, this inter-dependency between LETN and NPM1 is associated with the evolutionarily new variations of NPM1 and the coincidental emergence of LETN in higher primates. We propose that this human-specific protein–lncRNA axis renders an additional yet critical layer of regulation with high physiological relevance in both cancerous and normal developmental processes that require hyperactive nucleoli.
Satb2 neurons in the parabrachial nucleus mediate taste perception
Authors: Jarvie Brooke C. , Chen Jane Y. , King Hunter O. , Palmiter Richard D. 
Published: January 2021

AbstractThe neural circuitry mediating taste has been mapped out from the periphery to the cortex, but genetic identity of taste-responsive neurons has remained elusive. Here, we describe a population of neurons in the gustatory region of the parabrachial nucleus that express the transcription factor Satb2 and project to taste-associated regions, including the gustatory thalamus and insular cortex. Using calcium imaging in awake, freely licking mice, we show that Satb2 neurons respond to the five basic taste modalities. Optogenetic activation of these neurons enhances taste preferences, whereas chronic inactivation decreases the magnitude of taste preferences in both brief- and long-access taste tests. Simultaneous inactivation of Satb2 and calcitonin gene-related peptide neurons in the PBN abolishes responses to aversive tastes. These data suggest that taste information in the parabrachial nucleus is conveyed by multiple populations of neurons, including both Satb2 and calcitonin gene-related peptide neurons.
Perineuronal nets stabilize the grid cell network
Authors: Christensen Ane Charlotte , Lensjø Kristian Kinden , Lepperød Mikkel Elle , Dragly Svenn-Arne , Sutterud Halvard , Blackstad Jan Sigurd , Fyhn Marianne , Hafting Torkel 
Published: January 2021

AbstractGrid cells are part of a widespread network which supports navigation and spatial memory. Stable grid patterns appear late in development, in concert with extracellular matrix aggregates termed perineuronal nets (PNNs) that condense around inhibitory neurons. It has been suggested that PNNs stabilize synaptic connections and long-term memories, but their role in the grid cell network remains elusive. We show that removal of PNNs leads to lower inhibitory spiking activity, and reduces grid cells’ ability to create stable representations of a novel environment. Furthermore, in animals with disrupted PNNs, exposure to a novel arena corrupted the spatiotemporal relationships within grid cell modules, and the stored representations of a familiar arena. Finally, we show that PNN removal in entorhinal cortex distorted spatial representations in downstream hippocampal neurons. Together this work suggests that PNNs provide a key stabilizing element for the grid cell network.
Synthesis of arylamines and N-heterocycles by direct catalytic nitrogenation using N2
Authors: Wang Kai , Deng Zi-Hao , Xie Si-Jun , Zhai Dan-Dan , Fang Hua-Yi , Shi Zhang-Jie 
Published: January 2021

AbstractAmmonia and nitric acid are two key platform chemicals to introduce nitrogen atoms into organic molecules in chemical industry. Indeed, nitric acid is mostly produced through the oxidation of ammonia. The ideal nitrogenation would involve direct use of dinitrogen (N2) as a N source to construct N-containing organic molecules. Herein, we report an example of direct catalytic nitrogenation to afford valuable diarylamines, triarylamines, and N-heterocycles from easily available organohalides using dinitrogen (N2) as the nitrogen source in a one-pot/two-step protocol. With this method, 15N atoms are easily incorporated into organic molecules. Structurally diversified polyanilines are also generated in one pot, showing great potential for materials chemistry. In this protocol, lithium nitride, generated in situ with the use of lithium as a reductant, is confirmed as a key intermediate. This chemistry provides an alternative pathway for catalytic nitrogenation to synthesize highly valuable N-containing chemicals from dinitrogen.
Single ion qubit with estimated coherence time exceeding one hour
Authors: Wang Pengfei , Luan Chun-Yang , Qiao Mu , Um Mark , Zhang Junhua , Wang Ye , Yuan Xiao , Gu Mile , Zhang Jingning , Kim Kihwan 
Published: January 2021

AbstractRealizing a long coherence time quantum memory is a major challenge of current quantum technology. Until now, the longest coherence-time of a single qubit was reported as 660 s in a single 171Yb+ ion-qubit through the technical developments of sympathetic cooling and dynamical decoupling pulses, which addressed heating-induced detection inefficiency and magnetic field fluctuations. However, it was not clear what prohibited further enhancement. Here, we identify and suppress the limiting factors, which are the remaining magnetic-field fluctuations, frequency instability and leakage of the microwave reference-oscillator. Then, we observe the coherence time of around 5500 s for the 171Yb+ ion-qubit, which is the time constant of the exponential decay fit from the measurements up to 960 s. We also systematically study the decoherence process of the quantum memory by using quantum process tomography and analyze the results by applying recently developed resource theories of quantum memory and coherence. Our experimental demonstration will accelerate practical applications of quantum memories for various quantum information processing, especially in the noisy-intermediate-scale quantum regime.
Stable, high-performance, dendrite-free, seawater-based aqueous batteries
Authors: Tian Huajun , Li Zhao , Feng Guangxia , Yang Zhenzhong , Fox David , Wang Maoyu , Zhou Hua , Zhai Lei , Kushima Akihiro , Du Yingge , Feng Zhenxing , Shan Xiaonan , Yang Yang 
Published: January 2021

AbstractMetal anode instability, including dendrite growth, metal corrosion, and hetero-ions interference, occurring at the electrolyte/electrode interface of aqueous batteries, are among the most critical issues hindering their widespread use in energy storage. Herein, a universal strategy is proposed to overcome the anode instability issues by rationally designing alloyed materials, using Zn-M alloys as model systems (M = Mn and other transition metals). An in-situ optical visualization coupled with finite element analysis is utilized to mimic actual electrochemical environments analogous to the actual aqueous batteries and analyze the complex electrochemical behaviors. The Zn-Mn alloy anodes achieved stability over thousands of cycles even under harsh electrochemical conditions, including testing in seawater-based aqueous electrolytes and using a high current density of 80 mA cm−2. The proposed design strategy and the in-situ visualization protocol for the observation of dendrite growth set up a new milestone in developing durable electrodes for aqueous batteries and beyond.
NOD2 deficiency increases retrograde transport of secretory IgA complexes in Crohn’s disease
Authors: Rochereau Nicolas , Roblin Xavier , Michaud Eva , Gayet Rémi , Chanut Blandine , Jospin Fabienne , Corthésy Blaise , Paul Stéphane 
Published: January 2021

AbstractIntestinal microfold cells are the primary pathway for translocation of secretory IgA (SIgA)-pathogen complexes to gut-associated lymphoid tissue. Uptake of SIgA/commensals complexes is important for priming adaptive immunity in the mucosa. This study aims to explore the effect of SIgA retrograde transport of immune complexes in Crohn’s disease (CD). Here we report a significant increase of SIgA transport in CD patients with NOD2-mutation compared to CD patients withoutNOD2mutation and/or healthy individuals. NOD2 has an effect in the IgA transport through human and mouse M cells by downregulating Dectin-1 and Siglec-5 expression, two receptors involved in retrograde transport. These findings define a mechanism of NOD2-mediated regulation of mucosal responses to intestinal microbiota, which is involved in CD intestinal inflammation and dysbiosis.
Highly explosive basaltic eruptions driven by CO2 exsolution
Authors: Allison Chelsea M. , Roggensack Kurt , Clarke Amanda B. 
Published: January 2021

AbstractThe most explosive basaltic scoria cone eruption yet documented (>20 km high plumes) occurred at Sunset Crater (Arizona) ca. 1085 AD by undetermined eruptive mechanisms. We present melt inclusion analysis, including bubble contents by Raman spectroscopy, yielding high total CO2 (approaching 6000 ppm) and S (~2000 ppm) with moderate H2O (~1.25 wt%). Two groups of melt inclusions are evident, classified by bubble vol%. Modeling of post-entrapment modification indicates that the group with larger bubbles formed as a result of heterogeneous entrapment of melt and exsolved CO2 and provides evidence for an exsolved CO2 phase at magma storage depths of ~15 km. We argue that this exsolved CO2 phase played a critical role in driving this explosive eruption, possibly analogous to H2O exsolution driving silicic caldera-forming eruptions. Because of their distinct gas compositions relative to silicic magmas (high S and CO2), even modest volume explosive basaltic eruptions could impact the atmosphere.
Optimizing respiratory virus surveillance networks using uncertainty propagation
Authors: Pei Sen , Teng Xian , Lewis Paul , Shaman Jeffrey 
Published: January 2021

AbstractInfectious disease prevention, control and forecasting rely on sentinel observations; however, many locations lack the capacity for routine surveillance. Here we show that, by using data from multiple sites collectively, accurate estimation and forecasting of respiratory diseases for locations without surveillance is feasible. We develop a framework to optimize surveillance sites that suppresses uncertainty propagation in a networked disease transmission model. Using influenza outbreaks from 35 US states, the optimized system generates better near-term predictions than alternate systems designed using population and human mobility. We also find that monitoring regional population centers serves as a reasonable proxy for the optimized network and could direct surveillance for diseases with limited records. The proxy method is validated using model simulations for 3,108 US counties and historical data for two other respiratory pathogens – human metapneumovirus and seasonal coronavirus – from 35 US states and can be used to guide systemic allocation of surveillance efforts.
Ultraviolet radiation drives mutations in a subset of mucosal melanomas
Authors: Mundra Piyushkumar A. , Dhomen Nathalie , Rodrigues Manuel , Mikkelsen Lauge Hjorth , Cassoux Nathalie , Brooks Kelly , Valpione Sara , Reis-Filho Jorge S. , Heegaard Steffen , Stern Marc-Henri , Roman-Roman Sergio , Marais Richard 
Published: January 2021

AbstractAlthough identified as the key environmental driver of common cutaneous melanoma, the role of ultraviolet radiation (UVR)-induced DNA damage in mucosal melanoma is poorly defined. We analyze 10 mucosal melanomas of conjunctival origin by whole genome sequencing and our data shows a predominance of UVR-associated single base substitution signature 7 (SBS7) in the majority of the samples. Our data shows mucosal melanomas with SBS7 dominance have similar genomic patterns to cutaneous melanomas and therefore this subset should not be excluded from treatments currently used for common cutaneous melanoma.
Development and structural basis of a two-MAb cocktail for treating SARS-CoV-2 infections
Authors: Zhang Chao , Wang Yifan , Zhu Yuanfei , Liu Caixuan , Gu Chenjian , Xu Shiqi , Wang Yalei , Zhou Yu , Wang Yanxing , Han Wenyu , Hong Xiaoyu , Yang Yong , Zhang Xueyang , Wang Tingfeng , Xu Cong , Hong Qin , Wang Shutian , Zhao Qiaoyu , Qiao Weihua , Zang Jinkai , Kong Liangliang , Wang Fangfang , Wang Haikun , Qu Di , Lavillette Dimitri , Tang Hong , Deng Qiang , Xie Youhua , Cong Yao , Huang Zhong 
Published: January 2021

AbstractThe ongoing pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutralizing antibodies against SARS-CoV-2 are an option for drug development for treating COVID-19. Here, we report the identification and characterization of two groups of mouse neutralizing monoclonal antibodies (MAbs) targeting the receptor-binding domain (RBD) on the SARS-CoV-2 spike (S) protein. MAbs 2H2 and 3C1, representing the two antibody groups, respectively, bind distinct epitopes and are compatible in formulating a noncompeting antibody cocktail. A humanized version of the 2H2/3C1 cocktail is found to potently neutralize authentic SARS-CoV-2 infection in vitro with half inhibitory concentration (IC50) of 12 ng/mL and effectively treat SARS-CoV-2-infected mice even when administered at as late as 24 h post-infection. We determine an ensemble of cryo-EM structures of 2H2 or 3C1 Fab in complex with the S trimer up to 3.8 Å resolution, revealing the conformational space of the antigen–antibody complexes and MAb-triggered stepwise allosteric rearrangements of the S trimer, delineating a previously uncharacterized dynamic process of coordinated binding of neutralizing antibodies to the trimeric S protein. Our findings provide important information for the development of MAb-based drugs for preventing and treating SARS-CoV-2 infections.
Small molecule targeting r(UGGAA)n disrupts RNA foci and alleviates disease phenotype in Drosophila model
Authors: Shibata Tomonori , Nagano Konami , Ueyama Morio , Ninomiya Kensuke , Hirose Tetsuro , Nagai Yoshitaka , Ishikawa Kinya , Kawai Gota , Nakatani Kazuhiko 
Published: January 2021

AbstractSynthetic small molecules modulating RNA structure and function have therapeutic potential for RNA diseases. Here we report our discovery that naphthyridine carbamate dimer (NCD) targets disease-causing r(UGGAA)nrepeat RNAs in spinocerebellar ataxia type 31 (SCA31). Structural analysis of the NCD-UGGAA/UGGAA complex by nuclear magnetic resonance (NMR) spectroscopy clarifies the mode of binding that recognizes four guanines in the UGGAA/UGGAA pentad by hydrogen bonding with four naphthyridine moieties of two NCD molecules. Biological studies show that NCD disrupts naturally occurring RNA foci built on r(UGGAA)nrepeat RNA known as nuclear stress bodies (nSBs) by interfering with RNA–protein interactions resulting in the suppression of nSB-mediated splicing events. Feeding NCD to larvae of theDrosophilamodel of SCA31 alleviates the disease phenotype induced by toxic r(UGGAA)nrepeat RNA. These studies demonstrate that small molecules targeting toxic repeat RNAs are a promising chemical tool for studies on repeat expansion diseases.
Imaging dynamic mTORC1 pathway activity in vivo reveals marked shifts that support time-specific inhibitor therapy in AML
Authors: Oki Toshihiko , Mercier Francois , Kato Hiroki , Jung Yookyung , McDonald Thomas O. , Spencer Joel A. , Mazzola Michael C. , van Gastel Nick , Lin Charles P. , Michor Franziska , Kitamura Toshio , Scadden David T. 
Published: January 2021

AbstractAcute myeloid leukemia (AML) is a high remission, high relapse fatal blood cancer. Although mTORC1 is a master regulator of cell proliferation and survival, its inhibitors have not performed well as AML treatments. To uncover the dynamics of mTORC1 activity in vivo, fluorescent probes are developed to track single cell proliferation, apoptosis and mTORC1 activity of AML cells in the bone marrow of live animals and to quantify these activities in the context of microanatomical localization and intra-tumoral heterogeneity. When chemotherapy drugs commonly used clinically are given to mice with AML, apoptosis is rapid, diffuse and not preferentially restricted to anatomic sites. Dynamic measurement of mTORC1 activity indicated a decline in mTORC1 activity with AML progression. However, at the time of maximal chemotherapy response, mTORC1 signaling is high and positively correlated with a leukemia stemness transcriptional profile. Cell barcoding reveals the induction of mTORC1 activity rather than selection of mTORC1 high cells and timed inhibition of mTORC1 improved the killing of AML cells. These data define the real-time dynamics of AML and the mTORC1 pathway in association with AML growth, response to and relapse after chemotherapy. They provide guidance for timed intervention with pathway-specific inhibitors.
High-fat diet-induced upregulation of exosomal phosphatidylcholine contributes to insulin resistance
Authors: Kumar Anil , Sundaram Kumaran , Mu Jingyao , Dryden Gerald W. , Sriwastva Mukesh K. , Lei Chao , Zhang Lifeng , Qiu Xiaolan , Xu Fangyi , Yan Jun , Zhang Xiang , Park Juw Won , Merchant Michael L. , Bohler Henry C. L. , Wang Baomei , Zhang Shuangqin , Qin Chao , Xu Ziying , Han Xianlin , McClain Craig J. , Teng Yun , Zhang Huang-Ge 
Published: January 2021

AbstractHigh-fat diet (HFD) decreases insulin sensitivity. How high-fat diet causes insulin resistance is largely unknown. Here, we show that lean mice become insulin resistant after being administered exosomes isolated from the feces of obese mice fed a HFD or from patients with type II diabetes. HFD altered the lipid composition of exosomes from predominantly phosphatidylethanolamine (PE) in exosomes from lean animals (L-Exo) to phosphatidylcholine (PC) in exosomes from obese animals (H-Exo). Mechanistically, we show that intestinal H-Exo is taken up by macrophages and hepatocytes, leading to inhibition of the insulin signaling pathway. Moreover, exosome-derived PC binds to and activates AhR, leading to inhibition of the expression of genes essential for activation of the insulin signaling pathway, including IRS-2, and its downstream genes PI3K and Akt. Together, our results reveal HFD-induced exosomes as potential contributors to the development of insulin resistance. Intestinal exosomes thus have potential as broad therapeutic targets.
Antibody neutralization of SARS-CoV-2 through ACE2 receptor mimicry
Authors: Ge Jiwan , Wang Ruoke , Ju Bin , Zhang Qi , Sun Jing , Chen Peng , Zhang Senyan , Tian Yuling , Shan Sisi , Cheng Lin , Zhou Bing , Song Shuo , Zhao Juanjuan , Wang Haiyan , Shi Xuanling , Ding Qiang , Liu Lei , Zhao Jincun , Zhang Zheng , Wang Xinquan , Zhang Linqi 
Published: January 2021

AbstractUnderstanding the mechanism for antibody neutralization of SARS-CoV-2 is critical for the development of effective therapeutics and vaccines. We recently isolated a large number of monoclonal antibodies from SARS-CoV-2 infected individuals. Here we select the top three most potent yet variable neutralizing antibodies for in-depth structural and functional analyses. Crystal structural comparisons reveal differences in the angles of approach to the receptor binding domain (RBD), the size of the buried surface areas, and the key binding residues on the RBD of the viral spike glycoprotein. One antibody, P2C-1F11, most closely mimics binding of receptor ACE2, displays the most potent neutralizing activity in vitro and conferred strong protection against SARS-CoV-2 infection in Ad5-hACE2-sensitized mice. It also occupies the largest binding surface and demonstrates the highest binding affinity to RBD. More interestingly, P2C-1F11 triggers rapid and extensive shedding of S1 from the cell-surface expressed spike glycoprotein, with only minimal such effect by the remaining two antibodies. These results offer a structural and functional basis for potent neutralization via disruption of the very first and critical steps for SARS-CoV-2 cell entry.
The histone H3-lysine 4-methyltransferase Mll4 regulates the development of growth hormone-releasing hormone-producing neurons in the mouse hypothalamus
Authors: Huisman Christian , Kim Young A. , Jeon Shin , Shin Bongjin , Choi Jeonghoon , Lim Su Jeong , Youn Sung Min , Park Younjung , K. C. Medha , Kim Sangsoo , Lee Soo-Kyung , Lee Seunghee , Lee Jae W. 
Published: January 2021

AbstractIn humans, inactivating mutations inMLL4, which encodes a histone H3-lysine 4-methyltransferase, lead to Kabuki syndrome (KS). While dwarfism is a cardinal feature of KS, the underlying etiology remains unclear. Here we report that Mll4 regulates the development of growth hormone-releasing hormone (GHRH)-producing neurons in the mouse hypothalamus. Our twoMll4mutant mouse models exhibit dwarfism phenotype and impairment of the developmental programs for GHRH-neurons. Our ChIP-seq analysis reveals that, in the developing mouse hypothalamus, Mll4 interacts with the transcription factor Nrf1 to trigger the expression of GHRH-neuronal genes. Interestingly, the deficiency ofMll4results in a marked reduction of histone marks of active transcription, while treatment with the histone deacetylase inhibitor AR-42 rescues the histone mark signature and restores GHRH-neuronal production inMll4mutant mice. Our results suggest that the developmental dysregulation of Mll4-directed epigenetic control of transcription plays a role in the development of GHRH-neurons and dwarfism phenotype in mice.
Excited-state vibration-polariton transitions and dynamics in nitroprusside
Authors: Grafton Andrea B. , Dunkelberger Adam D. , Simpkins Blake S. , Triana Johan F. , Hernández Federico J. , Herrera Felipe , Owrutsky Jeffrey C. 
Published: January 2021

AbstractStrong cavity coupling to molecular vibrations creates vibration-polaritons capable of modifying chemical reaction kinetics, product branching ratios, and charge transfer equilibria. However, the mechanisms impacting these molecular processes remain elusive. Furthermore, even basic elements determining the spectral properties of polaritons, such as selection rules, transition moments, and lifetimes are poorly understood. Here, we use two-dimensional infrared and filtered pump–probe spectroscopy to report clear spectroscopic signatures and relaxation dynamics of excited vibration-polaritons formed from the cavity-coupled NO band of nitroprusside. We apply an extended multi-level quantum Rabi model that predicts transition frequencies and strengths that agree well with our experiment. Notably, the polariton features decay ~3–4 times slower than the polariton dephasing time, indicating that they support incoherent population, a consequence of their partial matter character.