bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiscale causal networks identify VGF as a key regulator of Alzheimer’s disease
Authors: Beckmann Noam D. , Lin Wei-Jye , Wang Minghui , Cohain Ariella T. , Charney Alexander W. , Wang Pei , Ma Weiping , Wang Ying-Chih , Jiang Cheng , Audrain Mickael , Comella Phillip H. , Fakira Amanda K. , Hariharan Siddharth P. , Belbin Gillian M. , Girdhar Kiran , Levey Allan I. , Seyfried Nicholas T. , Dammer Eric B. , Duong Duc , Lah James J. , Haure-Mirande Jean-Vianney , Shackleton Ben , Fanutza Tomas , Blitzer Robert , Kenny Eimear , Zhu Jun , Haroutunian Vahram , Katsel Pavel , Gandy Sam , Tu Zhidong , Ehrlich Michelle E. , Zhang Bin , Salton Stephen R. , Schadt Eric E. 
Published: August 2020

AbstractThough discovered over 100 years ago, the molecular foundation of sporadic Alzheimer’s disease (AD) remains elusive. To better characterize the complex nature of AD, we constructed multiscale causal networks on a large human AD multi-omics dataset, integrating clinical features of AD, DNA variation, and gene- and protein-expression. These probabilistic causal models enabled detection, prioritization and replication of high-confidence master regulators of AD-associated networks, including the top predicted regulator, VGF. Overexpression of neuropeptide precursor VGF in 5xFAD mice partially rescued beta-amyloid-mediated memory impairment and neuropathology. Molecular validation of network predictions downstream of VGF was also achieved in this AD model, with significant enrichment for homologous genes identified as differentially expressed in 5xFAD brains overexpressing VGF. Our findings support a causal role for VGF in protecting against AD pathogenesis and progression.
Undinarchaeota illuminate DPANN phylogeny and the impact of gene transfer on archaeal evolution
Authors: Dombrowski Nina , Williams Tom A. , Sun Jiarui , Woodcroft Benjamin J. , Lee Jun-Hoe , Minh Bui Quang , Rinke Christian , Spang Anja 
Published: August 2020

AbstractThe recently discovered DPANN archaea are a potentially deep-branching, monophyletic radiation of organisms with small cells and genomes. However, the monophyly and early emergence of the various DPANN clades and their role in life’s evolution are debated. Here, we reconstructed and analysed genomes of an uncharacterized archaeal phylum (CandidatusUndinarchaeota), revealing that its members have small genomes and, while potentially being able to conserve energy through fermentation, likely depend on partner organisms for the acquisition of certain metabolites. Our phylogenomic analyses robustly place Undinarchaeota as an independent lineage between two highly supported ‘DPANN’ clans. Further, our analyses suggest that DPANN have exchanged core genes with their hosts, adding to the difficulty of placing DPANN in the tree of life. This pattern can be sufficiently dominant to allow identifying known symbiont-host clades based on routes of gene transfer. Together, our work provides insights into the origins and evolution of DPANN and their hosts.
Triacylglycerols sequester monotopic membrane proteins to lipid droplets
Authors: Caillon Lucie , Nieto Vincent , Gehan Pauline , Omrane Mohyeddine , Rodriguez Nicolas , Monticelli Luca , Thiam Abdou Rachid 
Published: August 2020

AbstractTriacylglycerols (TG) are synthesized at the endoplasmic reticulum (ER) bilayer and packaged into organelles called lipid droplets (LDs). LDs are covered by a single phospholipid monolayer contiguous with the ER bilayer. This connection is used by several monotopic integral membrane proteins, with hydrophobic membrane association domains (HDs), to diffuse between the organelles. However, how proteins partition between ER and LDs is not understood. Here, we employed synthetic model systems and found that HD-containing proteins strongly prefer monolayers and returning to the bilayer is unfavorable. This preference for monolayers is due to a higher affinity of HDs for TG over membrane phospholipids. Protein distribution is regulated by PC/PE ratio via alterations in monolayer packing and HD-TG interaction. Thus, HD-containing proteins appear to non-specifically accumulate to the LD surface. In cells, protein editing mechanisms at the ER membrane would be necessary to prevent unspecific relocation of HD-containing proteins to LDs.
Discovery of the cryptic function of terpene cyclases as aromatic prenyltransferases
Authors: He Haibing , Bian Guangkai , Herbst-Gervasoni Corey J. , Mori Takahiro , Shinsky Stephen A. , Hou Anwei , Mu Xin , Huang Minjian , Cheng Shu , Deng Zixin , Christianson David W. , Abe Ikuro , Liu Tiangang 
Published: August 2020

AbstractCatalytic versatility is an inherent property of many enzymes. In nature, terpene cyclases comprise the foundation of molecular biodiversity as they generate diverse hydrocarbon scaffolds found in thousands of terpenoid natural products. Here, we report that the catalytic activity of the terpene cyclases AaTPS and FgGS can be switched from cyclase to aromatic prenyltransferase at basic pH to generate prenylindoles. The crystal structures of AaTPS and FgGS provide insights into the catalytic mechanism of this cryptic function. Moreover, aromatic prenyltransferase activity discovered in other terpene cyclases indicates that this cryptic function is broadly conserved among the greater family of terpene cyclases. We suggest that this cryptic function is chemoprotective for the cell by regulating isoprenoid diphosphate concentrations so that they are maintained below toxic thresholds.
Synthesis and assembly of extended quintulene
Authors: Hou Hao , Zhao Xin-Jing , Tang Chun , Ju Yang-Yang , Deng Ze-Ying , Wang Xin-Rong , Feng Liu-Bin , Lin Dong-Hai , Hou Xu , Narita Akimitsu , Müllen Klaus , Tan Yuan-Zhi 
Published: August 2020

AbstractQuintulene, a non-graphitic cycloarene with fivefold symmetry, has remained synthetically elusive due to its high molecular strain originating from its curved structure. Here we report the construction of extended quintulene, which was unambiguously characterized by mass and NMR spectroscopy. The extended quintulene represents a naturally curved nanocarbon based on its conical molecular geometry. It undergoes dimerization in solution via π−π stacking to form a metastable, but isolable bilayer complex. Thermodynamic and kinetic characterization reveals the dimerization process as entropy-driven and following second-order kinetics with a high activation energy. These findings provide a deeper understanding of the assembly of conical nanocarbons. Comparison of optical properties of monomer and dimer points toward a H-type interlayer coupling in the dimer.
Visualizing the enzyme mechanism of mevalonate diphosphate decarboxylase
Authors: Chen Chun-Liang , Paul Lake N. , Mermoud James C. , Steussy Calvin Nicklaus , Stauffacher Cynthia V. 
Published: August 2020

AbstractMevalonate diphosphate decarboxylases (MDDs) catalyze the ATP-dependent-Mg2+-decarboxylation of mevalonate-5-diphosphate (MVAPP) to produce isopentenyl diphosphate (IPP), which is essential in both eukaryotes and prokaryotes for polyisoprenoid synthesis. The substrates, MVAPP and ATP, have been shown to bind sequentially to MDD. Here we report crystals in which the enzyme remains active, allowing the visualization of conformational changes in Enterococcus faecalis MDD that describe sequential steps in an induced fit enzymatic reaction. Initial binding of MVAPP modulates the ATP binding pocket with a large loop movement. Upon ATP binding, a phosphate binding loop bends over the active site to recognize ATP and bring the molecules to their catalytically favored configuration. Positioned substrates then can chelate two Mg2+ ions for the two steps of the reaction. Closure of the active site entrance brings a conserved lysine to trigger dissociative phosphoryl transfer of γ-phosphate from ATP to MVAPP, followed by the production of IPP.
Reversal of pre-existing NGFR-driven tumor and immune therapy resistance
Authors: Boshuizen Julia , Vredevoogd David W. , Krijgsman Oscar , Ligtenberg Maarten A. , Blankenstein Stephanie , de Bruijn Beaunelle , Frederick Dennie T. , Kenski Juliana C. N. , Parren Mara , Brüggemann Marieke , Madu Max F. , Rozeman Elisa A. , Song Ji-Ying , Horlings Hugo M. , Blank Christian U. , van Akkooi Alexander C. J. , Flaherty Keith T. , Boland Genevieve M. , Peeper Daniel S. 
Published: August 2020

AbstractMelanomas can switch to a dedifferentiated cell state upon exposure to cytotoxic T cells. However, it is unclear whether such tumor cells pre-exist in patients and whether they can be resensitized to immunotherapy. Here, we chronically expose (patient-derived) melanoma cell lines to differentiation antigen-specific cytotoxic T cells and observe strong enrichment of a pre-existing NGFRhi population. These fractions are refractory also to T cells recognizing non-differentiation antigens, as well as to BRAF + MEK inhibitors. NGFRhi cells induce the neurotrophic factor BDNF, which contributes to T cell resistance, as does NGFR. In melanoma patients, a tumor-intrinsic NGFR signature predicts anti-PD-1 therapy resistance, and NGFRhi tumor fractions are associated with immune exclusion. Lastly, pharmacologic NGFR inhibition restores tumor sensitivity to T cell attack in vitro and in melanoma xenografts. These findings demonstrate the existence of a stable and pre-existing NGFRhi multitherapy-refractory melanoma subpopulation, which ought to be eliminated to revert intrinsic resistance to immunotherapeutic intervention.
Revealing the role of crystal orientation of protective layers for stable zinc anode
Authors: Zhang Qi , Luan Jingyi , Huang Xiaobing , Wang Qi , Sun Dan , Tang Yougen , Ji Xiaobo , Wang Haiyan 
Published: August 2020

AbstractRechargeable aqueous zinc-ion batteries are a promising candidate for next-generation energy storage devices. However, their practical application is limited by the severe safety issue caused by uncontrollable dendrite growth on zinc anodes. Here we develop faceted titanium dioxide with relatively low zinc affinity, which can restrict dendrite formation and homogenize zinc deposition when served as the protective layer on zinc anodes. The as-prepared zinc anodes can be stripped and plated steadily for more than 460 h with low voltage hysteresis and flat voltage plateau in symmetric cells. This work reveals the key role of crystal orientation in zinc affinity and its internal mechanism is suitable for various crystal materials applied in the surface modification of other metal anodes such as lithium and sodium.
A neural circuit encoding mating states tunes defensive behavior in Drosophila
Authors: Liu Chenxi , Zhang Bei , Zhang Liwei , Yang Tingting , Zhang Zhewei , Gao Zihua , Zhang Wei 
Published: August 2020

AbstractSocial context can dampen or amplify the perception of touch, and touch in turn conveys nuanced social information. However, the neural mechanism behind social regulation of mechanosensation is largely elusive. Here we report that fruit flies exhibit a strong defensive response to mechanical stimuli to their wings. In contrast, virgin female flies being courted by a male show a compromised defensive response to the stimuli, but following mating the response is enhanced. This state-dependent switch is mediated by a functional reconfiguration of a neural circuit labelled with the Tmc-L gene in the ventral nerve cord. The circuit receives excitatory inputs from peripheral mechanoreceptors and coordinates the defensive response. While male cues suppress it via a doublesex (dsx) neuronal pathway, mating sensitizes it by stimulating a group of uterine neurons and consequently activating a leucokinin-dependent pathway. Such a modulation is crucial for the balance between defense against body contacts and sexual receptivity.
A nonenzymatic method for cleaving polysaccharides to yield oligosaccharides for structural analysis
Authors: Amicucci Matthew J. , Nandita Eshani , Galermo Ace G. , Castillo Juan Jose , Chen Siyu , Park Dayoung , Smilowitz Jennifer T. , German J. Bruce , Mills David A. , Lebrilla Carlito B. 
Published: August 2020

AbstractPolysaccharides are the most abundant biomolecules in nature, but are the least understood in terms of their chemical structures and biological functions. Polysaccharides cannot be simply sequenced because they are often highly branched and lack a uniform structure. Furthermore, large polymeric structures cannot be directly analyzed by mass spectrometry techniques, a problem that has been solved for polynucleotides and proteins. While restriction enzymes have advanced genomic analysis, and trypsin has advanced proteomic analysis, there has been no equivalent enzyme for universal polysaccharide digestion. We describe the development and application of a chemical method for producing oligosaccharides from polysaccharides. The released oligosaccharides are characterized by advanced liquid chromatography–mass spectrometry (LC–MS) methods with high sensitivity, accuracy and throughput. The technique is first used to identify polysaccharides by oligosaccharide fingerprinting. Next, the polysaccharide compositions of food and feces are determined, further illustrating the utility of technique in food and clinical studies.
Distinct thalamocortical network dynamics are associated with the pathophysiology of chronic low back pain
Authors: Tu Yiheng , Fu Zening , Mao Cuiping , Falahpour Maryam , Gollub Randy L. , Park Joel , Wilson Georgia , Napadow Vitaly , Gerber Jessica , Chan Suk-Tak , Edwards Robert R. , Kaptchuk Ted J. , Liu Thomas , Calhoun Vince , Rosen Bruce , Kong Jian 
Published: August 2020

AbstractThalamocortical dysrhythmia is a key pathology of chronic neuropathic pain, but few studies have investigated thalamocortical networks in chronic low back pain (cLBP) given its non-specific etiology and complexity. Using fMRI, we propose an analytical pipeline to identify abnormal thalamocortical network dynamics in cLBP patients and validate the findings in two independent cohorts. We first identify two reoccurring dynamic connectivity states and their associations with chronic and temporary pain. Further analyses show that cLBP patients have abnormal connectivity between the ventral lateral/posterolateral nucleus (VL/VPL) and postcentral gyrus (PoCG) and between the dorsal/ventral medial nucleus and insula in the less frequent connectivity state, and temporary pain exacerbation alters connectivity between the VL/VPL and PoCG and the default mode network in the more frequent connectivity state. These results extend current findings on thalamocortical dysfunction and dysrhythmia in chronic pain and demonstrate that cLBP pathophysiology and clinical pain intensity are associated with distinct thalamocortical network dynamics.
Transient dormant monomer states for supramolecular polymers with low dispersity
Authors: Jalani Krishnendu , Das Anjali Devi , Sasmal Ranjan , Agasti Sarit S. , George Subi J. 
Published: August 2020

AbstractTemporally controlled cooperative and living supramolecular polymerization by the buffered release of monomers has been recently introduced as an important concept towards obtaining monodisperse and multicomponent self-assembled materials. In synthetic, dynamic supramolecular polymers, this requires efficient design strategies for the dormant, inactive states of the monomers to kinetically retard the otherwise spontaneous nucleation process. However, a generalized design principle for the dormant monomer states to expand the scope of precision supramolecular polymers has not been established yet, due to the enormous differences in the mechanism, energetic parameters of self-assembly and monomer exchange dynamics of the diverse class of supramolecular polymers. Here we report the concept of transient dormant states of monomers generated by redox reactions as a predictive general design to achieve monodisperse supramolecular polymers of electronically active, chromophoric or donor-acceptor, monomers. The concept has been demonstrated with charge-transfer supramolecular polymers with an alternating donor-acceptor sequence.
Enthalpy-entropy compensation of atomic diffusion originates from softening of low frequency phonons
Authors: Gelin Simon , Champagne-Ruel Alexandre , Mousseau Normand 
Published: August 2020

AbstractExperimental data accumulated over more than 120 years show not only that diffusion coefficients of impurities ordinarily obey the Arrhenius law in crystalline solids, but also that diffusion pre-exponential factors measured in a same solid increase exponentially with activation energies. This so-called compensation effect has been argued to result from a universal positive linear relationship between entropic contributions and energy barriers to diffusion. However, no physical model of entropy has ever been successfully tested against experimental compensation data. Here, we solve this decades-old problem by demonstrating that atomistically computed harmonic vibrational entropic contributions account for most of compensation effects in silicon and aluminum. We then show that, on average, variations of atomic interactions along diffusion reaction paths simultaneously soften low frequency phonons and stiffen high frequency ones; because relative frequency variations are larger in the lower region of the spectrum, softening generally prevails over stiffening and entropy ubiquitously increases with energy.
Atomic-scale phase separation induced clustering of solute atoms
Authors: Zou Lianfeng , Cao Penghui , Lei Yinkai , Zakharov Dmitri , Sun Xianhu , House Stephen D. , Luo Langli , Li Jonathan , Yang Yang , Yin Qiyue , Chen Xiaobo , Li Chaoran , Qin Hailang , Stach Eric A. , Yang Judith C. , Wang Guofeng , Zhou Guangwen 
Published: August 2020

AbstractDealloying typically occurs via the chemical dissolution of an alloy component through a corrosion process. In contrast, here we report an atomic-scale nonchemical dealloying process that results in the clustering of solute atoms. We show that the disparity in the adatom–substrate exchange barriers separate Cu adatoms from a Cu–Au mixture, leaving behind a fluid phase enriched with Au adatoms that subsequently aggregate into supported clusters. Using dynamic, atomic-scale electron microscopy observations and theoretical modeling, we delineate the atomic-scale mechanisms associated with the nucleation, rotation and amorphization–crystallization oscillations of the Au clusters. We expect broader applicability of the results because the phase separation process is dictated by the inherent asymmetric adatom-substrate exchange barriers for separating dissimilar atoms in multicomponent materials.
Vernier frequency division with dual-microresonator solitons
Authors: Wang Beichen , Yang Zijiao , Zhang Xiaobao , Yi Xu 
Published: August 2020

AbstractMicroresonator solitons are critical to miniaturize optical frequency combs to chip scale and have the potential to revolutionize spectroscopy, metrology and timing. With the reduction of resonator diameter, high repetition rates up to 1 THz become possible, and they are advantageous to wavelength multiplexing, coherent sampling, and self-referencing. However, the detection of comb repetition rate, the precursor to all comb-based applications, becomes challenging at these repetition rates due to the limited bandwidth of photodiodes and electronics. Here, we report a dual-comb Vernier frequency division method to vastly reduce the required electrical bandwidth. Free-running 216 GHz “Vernier” solitons sample and divide the main soliton’s repetition frequency from 197 GHz to 995 MHz through electrical processing of a pair of low frequency dual-comb beat notes. Our demonstration relaxes the instrumentation requirement for microcomb repetition rate detection, and could be applied for optical clocks, optical frequency division, and microwave photonics.
Topoisomerase 1 prevents replication stress at R-loop-enriched transcription termination sites
Authors: Promonet Alexy , Padioleau Ismaël , Liu Yaqun , Sanz Lionel , Biernacka Anna , Schmitz Anne-Lyne , Skrzypczak Magdalena , Sarrazin Amélie , Mettling Clément , Rowicka Maga , Ginalski Krzysztof , Chedin Frédéric , Chen Chun-Long , Lin Yea-Lih , Pasero Philippe 
Published: August 2020

AbstractR-loops have both positive and negative impacts on chromosome functions. To identify toxic R-loops in the human genome, here, we map RNA:DNA hybrids, replication stress markers and DNA double-strand breaks (DSBs) in cells depleted for Topoisomerase I (Top1), an enzyme that relaxes DNA supercoiling and prevents R-loop formation. RNA:DNA hybrids are found at both promoters (TSS) and terminators (TTS) of highly expressed genes. In contrast, the phosphorylation of RPA by ATR is only detected at TTS, which are preferentially replicated in a head-on orientation relative to the direction of transcription. In Top1-depleted cells, DSBs also accumulate at TTS, leading to persistent checkpoint activation, spreading of γ-H2AX on chromatin and global replication fork slowdown. These data indicate that fork pausing at the TTS of highly expressed genes containing R-loops prevents head-on conflicts between replication and transcription and maintains genome integrity in a Top1-dependent manner.
Storage and retrieval of microwave pulses with molecular spin ensembles
Authors: Bonizzoni Claudio , Ghirri Alberto , Santanni Fabio , Atzori Matteo , Sorace Lorenzo , Sessoli Roberta , Affronte Marco 
Published: August 2020

AbstractHybrid architectures combining complementary quantum systems will be largely used in quantum technologies and the integration of different components is one of the key issues. Thanks to their long coherence times and the easy manipulation with microwave pulses, electron spins hold a potential for the realization of quantum memories. Here, we test diluted oxovanadium tetraphenyl porphyrin (VO(TPP)) as a prototypical molecular spin system for the Storage/Retrieval of microwave pulses when embedded into planar superconducting microwave resonators. We first investigate the efficiency of several pulse sequences in addressing the spins. The Carr-Purcell and the Uhrig Dynamical Decoupling enhance the memory time up to three times with threeπpulses. We then successfully store and retrieve trains of up to 5 small pulses by using a single recovery pulse. These results demonstrate the memory capabilities of molecular spin ensembles when embedded into quantum circuits.
Novel multiparameter correlates of Coxiella burnetii infection and vaccination identified by longitudinal deep immune profiling
Authors: Reeves P. M. , Raju Paul S. , Baeten L. , Korek S. E. , Yi Y. , Hess J. , Sobell D. , Scholzen A. , Garritsen A. , De Groot A. S. , Moise L. , Brauns T. , Bowen R. , Sluder A. E. , Poznansky M. C. 
Published: August 2020

AbstractQ-fever is a flu-like illness caused byCoxiella burnetii(Cb), a highly infectious intracellular bacterium. There is an unmet need for a safe and effective vaccine for Q-fever. Correlates of immune protection toCbinfection are limited. We proposed that analysis by longitudinal high dimensional immune (HDI) profiling using mass cytometry combined with other measures of vaccination and protection could be used to identify novel correlates of effective vaccination and control ofCbinfection. Using a vaccine-challenge model in HLA-DR transgenic mice, we demonstrated significant alterations in circulating T-cell and innate immune populations that distinguished vaccinated from naïve mice within 10 days, and persisted until at least 35 days post-vaccination. Following challenge, vaccinated mice exhibited reduced bacterial burden and splenomegaly, along with distinct effector T-cell and monocyte profiles. Correlation of HDI data to serological and pathological measurements was performed. Our data indicate a Th1-biased response toCb, consistent with previous reports, and identify Ly6C, CD73, and T-bet expression in T-cell, NK-cell, and monocytic populations as distinguishing features between vaccinated and naïve mice. This study refines the understanding of the integrated immune response toCbvaccine and challenge, which can inform the assessment of candidate vaccines forCb.