bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human anogenital monocyte-derived dendritic cells and langerin+cDC2 are major HIV target cells
Authors: Rhodes Jake W. , Botting Rachel A. , Bertram Kirstie M. , Vine Erica E. , Rana Hafsa , Baharlou Heeva , Vegh Peter , O’Neil Thomas R. , Ashhurst Anneliese S. , Fletcher James , Parnell Grant P. , Graham J. Dinny , Nasr Najla , Lim Jake J. K. , Barnouti Laith , Haertsch Peter , Gosselink Martijn P. , Di Re Angelina , Reza Faizur , Ctercteko Grahame , Jenkins Gregory J. , Brooks Andrew J. , Patrick Ellis , Byrne Scott N. , Hunter Eric , Haniffa Muzlifah A. , Cunningham Anthony L. , Harman Andrew N. 
Published: April 2021

AbstractTissue mononuclear phagocytes (MNP) are specialised in pathogen detection and antigen presentation. As such they deliver HIV to its primary target cells; CD4 T cells. Most MNP HIV transmission studies have focused on epithelial MNPs. However, as mucosal trauma and inflammation are now known to be strongly associated with HIV transmission, here we examine the role of sub-epithelial MNPs which are present in a diverse array of subsets. We show that HIV can penetrate the epithelial surface to interact with sub-epithelial resident MNPs in anogenital explants and define the full array of subsets that are present in the human anogenital and colorectal tissues that HIV may encounter during sexual transmission. In doing so we identify two subsets that preferentially take up HIV, become infected and transmit the virus to CD4 T cells; CD14+CD1c+ monocyte-derived dendritic cells and langerin-expressing conventional dendritic cells 2 (cDC2).
Astigmatic traction force microscopy (aTFM)
Authors: Li Di , Colin-York Huw , Barbieri Liliana , Javanmardi Yousef , Guo Yuting , Korobchevskaya Kseniya , Moeendarbary Emad , Li Dong , Fritzsche Marco 
Published: April 2021

AbstractQuantifying small, rapidly progressing three-dimensional forces generated by cells remains a major challenge towards a more complete understanding of mechanobiology. Traction force microscopy is one of the most broadly applied force probing technologies but ascertaining three-dimensional information typically necessitates slow, multi-frame z-stack acquisition with limited sensitivity. Here, by performing traction force microscopy using fast single-frame astigmatic imaging coupled with total internal reflection fluorescence microscopy we improve the temporal resolution of three-dimensional mechanical force quantification up to 10-fold compared to its related super-resolution modalities. 2.5D astigmatic traction force microscopy (aTFM) thus enables live-cell force measurements approaching physiological sensitivity.
Reovirus directly engages integrin to recruit clathrin for entry into host cells
Authors: Koehler Melanie , Petitjean Simon J. L. , Yang Jinsung , Aravamudhan Pavithra , Somoulay Xayathed , Lo Giudice Cristina , Poncin Mégane A. , Dumitru Andra C. , Dermody Terence S. , Alsteens David 
Published: April 2021

AbstractReovirus infection requires the concerted action of viral and host factors to promote cell entry. After interaction of reovirus attachment protein σ1 with cell-surface carbohydrates and proteinaceous receptors, additional host factors mediate virus internalization. In particular, β1 integrin is required for endocytosis of reovirus virions following junctional adhesion molecule A (JAM-A) binding. While integrin-binding motifs in the surface-exposed region of reovirus capsid protein λ2 are thought to mediate integrin interaction, evidence for direct β1 integrin-reovirus interactions and knowledge of how integrins function to mediate reovirus entry is lacking. Here, we use single-virus force spectroscopy and confocal microscopy to discover a direct interaction between reovirus and β1 integrins. Comparison of interactions between reovirus disassembly intermediates as well as mutants and β1 integrin show that λ2 is the integrin ligand. Finally, using fluidic force microscopy, we demonstrate a functional role for β1 integrin interaction in promoting clathrin recruitment to cell-bound reovirus. Our study demonstrates a direct interaction between reovirus and β1 integrins and offers insights into the mechanism of reovirus cell entry. These results provide new perspectives for the development of efficacious antiviral therapeutics and the engineering of improved viral gene delivery and oncolytic vectors.
Optical spin-state polarization in a binuclear europium complex towards molecule-based coherent light-spin interfaces
Authors: Kumar Kuppusamy Senthil , Serrano Diana , Nonat Aline M. , Heinrich Benoît , Karmazin Lydia , Charbonnière Loïc J. , Goldner Philippe , Ruben Mario 
Published: April 2021

AbstractThe success of the emerging field of solid-state optical quantum information processing (QIP) critically depends on the access to resonant optical materials. Rare-earth ion (REI)-based molecular systems, whose quantum properties could be tuned taking advantage of molecular engineering strategies, are one of the systems actively pursued for the implementation of QIP schemes. Herein, we demonstrate the efficient polarization of ground-state nuclear spins—a fundamental requirement for all-optical spin initialization and addressing—in a binuclear Eu(III) complex, featuring inhomogeneously broadened 5D0 → 7F0 optical transition. At 1.4 K, long-lived spectral holes have been burnt in the transition: homogeneous linewidth (Γh) = 22 ± 1 MHz, which translates as optical coherence lifetime (T2opt) = 14.5 ± 0.7 ns, and ground-state spin population lifetime (T1spin) = 1.6 ± 0.4 s have been obtained. The results presented in this study could be a progressive step towards the realization of molecule-based coherent light-spin QIP interfaces.
Autonomous Purkinje cell activation instructs bidirectional motor learning through evoked dendritic calcium signaling
Authors: Bonnan Audrey , Rowan Matthew M. J. , Baker Christopher A. , Bolton M. McLean , Christie Jason M. 
Published: April 2021

AbstractThe signals in cerebellar Purkinje cells sufficient to instruct motor learning have not been systematically determined. Therefore, we applied optogenetics in mice to autonomously excite Purkinje cells and measured the effect of this activity on plasticity induction and adaptive behavior. Ex vivo, excitation of channelrhodopsin-2-expressing Purkinje cells elicits dendritic Ca2+ transients with high-intensity stimuli initiating dendritic spiking that additionally contributes to the Ca2+ response. Channelrhodopsin-2-evoked Ca2+ transients potentiate co-active parallel fiber synapses; depression occurs when Ca2+ responses were enhanced by dendritic spiking. In vivo, optogenetic Purkinje cell activation drives an adaptive decrease in vestibulo-ocular reflex gain when vestibular stimuli are paired with relatively small-magnitude Purkinje cell Ca2+ responses. In contrast, pairing with large-magnitude Ca2+ responses increases vestibulo-ocular reflex gain. Optogenetically induced plasticity and motor adaptation are dependent on endocannabinoid signaling, indicating engagement of this pathway downstream of Purkinje cell Ca2+ elevation. Our results establish a causal relationship among Purkinje cell Ca2+ signal size, opposite-polarity plasticity induction, and bidirectional motor learning.
Increased respiratory morbidity associated with exposure to a mature volcanic plume from a large Icelandic fissure eruption
Authors: Carlsen Hanne Krage , Ilyinskaya Evgenia , Baxter Peter J. , Schmidt Anja , Thorsteinsson Throstur , Pfeffer Melissa Anne , Barsotti Sara , Dominici Francesca , Finnbjornsdottir Ragnhildur Gudrun , Jóhannsson Thorsteinn , Aspelund Thor , Gislason Thorarinn , Valdimarsdóttir Unnur , Briem Haraldur , Gudnason Thorolfur 
Published: April 2021

AbstractThe 2014–15 Holuhraun eruption in Iceland was the largest fissure eruption in over 200 years, emitting prodigious amounts of gas and particulate matter into the troposphere. Reykjavík, the capital area of Iceland (250 km from eruption site) was exposed to air pollution events from advection of (i) a relatively young and chemically primitive volcanic plume with a high sulphur dioxide gas (SO2) to sulphate PM (SO42−) ratio, and (ii) an older and chemically mature volcanic plume with a low SO2/SO42− ratio. Whereas the advection and air pollution caused by the primitive plume were successfully forecast and forewarned in public advisories, the mature plume was not. Here, we show that exposure to the mature plume is associated with an increase in register-measured health care utilisation for respiratory disease by 23% (95% CI 19.7–27.4%) and for asthma medication dispensing by 19.3% (95% CI 9.6–29.1%). Absence of public advisories is associated with increases in visits to primary care medical doctors and to the hospital emergency department. We recommend that operational response to volcanic air pollution considers both primitive and mature types of plumes.
In-situ plasmonic tracking oxygen evolution reveals multistage oxygen diffusion and accumulating inhibition
Authors: Wang Jun-Gang , Shi Lifang , Su Yingying , Liu Liwei , Yang Zhenzhong , Huang Rong , Xie Jing , Tian Yang , Li Di 
Published: April 2021

AbstractUnderstanding mass transfer processes concomitant with electrochemical conversion for gas evolution reactions at the electrode-electrolyte interface plays a key role in advancing renewable energy storage and conversion. However, due to the complicated diffusion behavior of gas at the dynamic catalytic interfaces, it is still a great challenge to accurately portray mass transfer of gas during electrocatalysis process. Here, we track the diffusion of dissolved oxygen on Cu nanostructured plasmonic interface, which reveals multistage oxygen diffusion behaviors, including premature oxygen accumulation, spontaneous diffusion and accelerated oxygen dissipation. This work uncovers an accumulating inhibition effect on oxygen evolution arising from interfacial dissolved oxygen. With these knowledges, we develop a programmable potential scan strategy to eliminate interfacial gas products, which alleviates the concentration polarization, releases accessible actives sites and promotes electrocatalytic performance. Our findings provide a direct observation of the interfacial mass transfer processes that governs the kinetics of gas-involved multiphases catalysis.
The E3 ligase MREL57 modulates microtubule stability and stomatal closure in response to ABA
Authors: Dou Liru , He Kaikai , Peng Jialin , Wang Xiangfeng , Mao Tonglin 
Published: April 2021

AbstractRegulation of stomatal movement is critical for plant adaptation to environmental stresses. The microtubule cytoskeleton undergoes disassembly, which is critical for stomatal closure in response to abscisic acid (ABA). However, the mechanism underlying this regulation largely remains unclear. Here we show that a ubiquitin-26S proteasome (UPS)-dependent pathway mediates microtubule disassembly and is required for ABA-induced stomatal closure. Moreover, we identify and characterize the ubiquitin E3 ligase MREL57 (MICROTUBULE-RELATED E3 LIGASE57) and the microtubule-stabilizing protein WDL7 (WAVE-DAMPENED2-LIKE7) inArabidopsisand show that the MREL57-WDL7 module regulates microtubule disassembly to mediate stomatal closure in response to drought stress and ABA treatment. MREL57 interacts with, ubiquitinates and degrades WDL7, and this effect is clearly enhanced by ABA. ABA-induced stomatal closure and microtubule disassembly are significantly suppressed inmrel57mutants, and these phenotypes can be restored whenWDL7expression is decreased. Our results unravel UPS-dependent mechanisms and the role of an MREL57-WDL7 module in microtubule disassembly and stomatal closure in response to drought stress and ABA.
Therapeutic B-cell depletion reverses progression of Alzheimer’s disease
Authors: Kim Ki , Wang Xin , Ragonnaud Emeline , Bodogai Monica , Illouz Tomer , DeLuca Marisa , McDevitt Ross A. , Gusev Fedor , Okun Eitan , Rogaev Evgeny , Biragyn Arya 
Published: April 2021

AbstractThe function of B cells in Alzheimer’s disease (AD) is not fully understood. While immunoglobulins that target amyloid beta (Aβ) may interfere with plaque formation and hence progression of the disease, B cells may contribute beyond merely producing immunoglobulins. Here we show that AD is associated with accumulation of activated B cells in circulation, and with infiltration of B cells into the brain parenchyma, resulting in immunoglobulin deposits around Aβ plaques. Using three different murine transgenic models, we provide counterintuitive evidence that the AD progression requires B cells. Despite expression of the AD-fostering transgenes, the loss of B cells alone is sufficient to reduce Aβ plaque burden and disease-associated microglia. It reverses behavioral and memory deficits and restores TGFβ+ microglia, respectively. Moreover, therapeutic depletion of B cells at the onset of the disease retards AD progression in mice, suggesting that targeting B cells may also benefit AD patients.
Learning cis-regulatory principles of ADAR-based RNA editing from CRISPR-mediated mutagenesis
Authors: Liu Xin , Sun Tao , Shcherbina Anna , Li Qin , Jarmoskaite Inga , Kappel Kalli , Ramaswami Gokul , Das Rhiju , Kundaje Anshul , Li Jin Billy 
Published: April 2021

AbstractAdenosine-to-inosine (A-to-I) RNA editing catalyzed by ADAR enzymes occurs in double-stranded RNAs. Despite a compelling need towards predictive understanding of natural and engineered editing events, how the RNA sequence and structure determine the editing efficiency and specificity (i.e., cis-regulation) is poorly understood. We apply a CRISPR/Cas9-mediated saturation mutagenesis approach to generate libraries of mutations near three natural editing substrates at their endogenous genomic loci. We use machine learning to integrate diverse RNA sequence and structure features to model editing levels measured by deep sequencing. We confirm known features and identify new features important for RNA editing. Training and testing XGBoost algorithm within the same substrate yield models that explain 68 to 86 percent of substrate-specific variation in editing levels. However, the models do not generalize across substrates, suggesting complex and context-dependent regulation patterns. Our integrative approach can be applied to larger scale experiments towards deciphering the RNA editing code.
Extracellular cap domain is an essential component of the TRPV1 gating mechanism
Authors: Nadezhdin Kirill D. , Neuberger Arthur , Nikolaev Yury A. , Murphy Lyle A. , Gracheva Elena O. , Bagriantsev Sviatoslav N. , Sobolevsky Alexander I. 
Published: April 2021

AbstractTransient receptor potential (TRP) channels are polymodal molecular sensors involved in numerous physiological processes and implicated in a variety of human diseases. Several structures of the founding member of the TRP channel family, TRPV1, are available, all of which were determined for the protein missing the N- and C-termini and the extracellular S5-P-loop. Here, we present structures of the full-length thirteen-lined ground squirrel TRPV1 solved by cryo-EM. Our structures resolve the extracellular cap domain formed by the S5-P-loops and the C-terminus that wraps around the three-stranded β-sheet connecting elements of the TRPV1 intracellular skirt. The cap domain forms a dome above the pore’s extracellular entrance, with four portals leading to the ion conductance pathway. Deletion of the cap increases the TRPV1 average conductance, reduces the open probability and affects ion selectivity. Our data show that both the termini and the cap domain are critical determinants of TRPV1 function.
Discovery of higher-order topological insulators using the spin Hall conductivity as a topology signature
Authors: Costa Marcio , Schleder Gabriel R. , Mera Acosta Carlos , Padilha Antonio C. M. , Cerasoli Frank , Buongiorno Nardelli Marco , Fazzio Adalberto 
Published: April 2021

AbstractThe discovery and realization of topological insulators, a phase of matter which hosts metallic boundary states when the d-dimension insulating bulk is confined to (d − 1)-dimensions, led to several potential applications. Recently, it was shown that protected topological states can manifest in (d − 2)-dimensions, such as hinge and corner states for three- and two-dimensional systems, respectively. These nontrivial materials are named higher-order topological insulators (HOTIs). Here we show a connection between spin Hall effect and HOTIs using a combination of ab initio calculations and tight-binding modeling. The model demonstrates how a non-zero bulk midgap spin Hall conductivity (SHC) emerges within the HOTI phase. Following this, we performed high-throughput density functional theory calculations to find unknown HOTIs, using the SHC as a criterion. We calculated the SHC of 693 insulators resulting in seven stable two-dimensional HOTIs. Our work guides novel experimental and theoretical advances towards higher-order topological insulator realization and applications.
Synucleinopathy-associated pathogenesis in Parkinson’s disease and the potential for brain-derived neurotrophic factor
Authors: Miller Kathryn M. , Mercado Natosha M. , Sortwell Caryl E. 
Published: April 2021

AbstractThe lack of disease-modifying treatments for Parkinson’s disease (PD) is in part due to an incomplete understanding of the disease’s etiology. Alpha-synuclein (α-syn) has become a point of focus in PD due to its connection to both familial and idiopathic cases—specifically its localization to Lewy bodies (LBs), a pathological hallmark of PD. Within this review, we will present a comprehensive overview of the data linking synuclein-associated Lewy pathology with intracellular dysfunction. We first present the alterations in neuronal proteins and transcriptome associated with LBs in postmortem human PD tissue. We next compare these findings to those associated with LB-like inclusions initiated by in vitro exposure to α-syn preformed fibrils (PFFs) and highlight the profound and relatively unique reduction of brain-derived neurotrophic factor (BDNF) in this model. Finally, we discuss the multitude of ways in which BDNF offers the potential to exert disease-modifying effects on the basal ganglia. What remains unknown is the potential for BDNF to mitigate inclusion-associated dysfunction within the context of synucleinopathy. Collectively, this review reiterates the merit of using the PFF model as a tool to understand the physiological changes associated with LBs, while highlighting the neuroprotective potential of harnessing endogenous BDNF.
An artificial spiking quantum neuron
Authors: Kristensen Lasse Bjørn , Degroote Matthias , Wittek Peter , Aspuru-Guzik Alán , Zinner Nikolaj T. 
Published: April 2021

AbstractArtificial spiking neural networks have found applications in areas where the temporal nature of activation offers an advantage, such as time series prediction and signal processing. To improve their efficiency, spiking architectures often run on custom-designed neuromorphic hardware, but, despite their attractive properties, these implementations have been limited to digital systems. We describe an artificial quantum spiking neuron that relies on the dynamical evolution of two easy to implement Hamiltonians and subsequent local measurements. The architecture allows exploiting complex amplitudes and back-action from measurements to influence the input. This approach to learning protocols is advantageous in the case where the input and output of the system are both quantum states. We demonstrate this through the classification of Bell pairs which can be seen as a certification protocol. Stacking the introduced elementary building blocks into larger networks combines the spatiotemporal features of a spiking neural network with the non-local quantum correlations across the graph.
Lattice-shifted nematic quantum critical point in FeSe1−xSx
Authors: Chibani S. , Farina D. , Massat P. , Cazayous M. , Sacuto A. , Urata T. , Tanabe Y. , Tanigaki K. , Böhmer A. E. , Canfield P. C. , Merz M. , Karlsson S. , Strobel P. , Toulemonde P. , Paul I. , Gallais Y. 
Published: April 2021

AbstractWe report the evolution of nematic fluctuations in FeSe1−xSx single crystals as a function of Sulfur content x across the nematic quantum critical point (QCP) xc ~ 0.17 via Raman scattering. The Raman spectra in the B1g nematic channel consist of two components, but only the low energy one displays clear fingerprints of critical behavior and is attributed to itinerant carriers. Curie–Weiss analysis of the associated nematic susceptibility indicates a substantial effect of nemato-elastic coupling, which shifts the location of the nematic QCP. We argue that this lattice-induced shift likely explains the absence of any enhancement of the superconducting transition temperature at the QCP. The presence of two components in the nematic fluctuations spectrum is attributed to the dual aspect of electronic degrees of freedom in Hund’s metals, with both itinerant carriers and local moments contributing to the nematic susceptibility.
Force of infection: a determinant of vaccine efficacy?
Authors: Kaslow David C. 
Published: April 2021

AbstractVaccine efficacy (VE) can vary in different settings. Of the many proposed setting-dependent determinants of VE, force of infection (FoI) stands out as one of the most direct, proximate, and actionable. As highlighted by the COVID-19 pandemic, modifying FoI through non-pharmaceutical interventions (NPIs) use can significantly contribute to controlling transmission and reducing disease incidence and severity absent highly effective pharmaceutical interventions, such as vaccines. Given that NPIs reduce the FoI, the question arises as to if and to what degree FoI, and by extension NPIs, can modify VE, and more practically, as vaccines become available for a pathogen, whether and which NPIs should continue to be used in conjunction with vaccines to optimize controlling transmission and reducing disease incidence and severity.
Structural basis of nucleosome transcription mediated by Chd1 and FACT
Authors: Farnung Lucas , Ochmann Moritz , Engeholm Maik , Cramer Patrick 
Published: April 2021

AbstractEfficient transcription of RNA polymerase II (Pol II) through nucleosomes requires the help of various factors. Here we show biochemically that Pol II transcription through a nucleosome is facilitated by the chromatin remodeler Chd1 and the histone chaperone FACT when the elongation factors Spt4/5 and TFIIS are present. We report cryo-EM structures of transcribing Saccharomyces cerevisiae Pol II−Spt4/5−nucleosome complexes with bound Chd1 or FACT. In the first structure, Pol II transcription exposes the proximal histone H2A−H2B dimer that is bound by Spt5. Pol II has also released the inhibitory DNA-binding region of Chd1 that is poised to pump DNA toward Pol II. In the second structure, Pol II has generated a partially unraveled nucleosome that binds FACT, which excludes Chd1 and Spt5. These results suggest that Pol II progression through a nucleosome activates Chd1, enables FACT binding and eventually triggers transfer of FACT together with histones to upstream DNA.