bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional reprogramming during human osteoclast differentiation identifies regulators of osteoclast activity
Authors: Hansen Morten S. , Madsen Kaja , Price Maria , Søe Kent , Omata Yasunori , Zaiss Mario M. , Gorvin Caroline M. , Frost Morten , Rauch Alexander 
Published: January 2024

AbstractEnhanced osteoclastogenesis and osteoclast activity contribute to the development of osteoporosis, which is characterized by increased bone resorption and inadequate bone formation. As novel antiosteoporotic therapeutics are needed, understanding the genetic regulation of human osteoclastogenesis could help identify potential treatment targets. This study aimed to provide an overview of transcriptional reprogramming during human osteoclast differentiation. Osteoclasts were differentiated from CD14+ monocytes from eight female donors. RNA sequencing during differentiation revealed 8 980 differentially expressed genes grouped into eight temporal patterns conserved across donors. These patterns revealed distinct molecular functions associated with postmenopausal osteoporosis susceptibility genes based on RNA from iliac crest biopsies and bone mineral density SNPs. Network analyses revealed mutual dependencies between temporal expression patterns and provided insight into subtype-specific transcriptional networks. The donor-specific expression patterns revealed genes at the monocyte stage, such as filamin B (FLNB) and oxidized low-density lipoprotein receptor 1 (OLR1, encoding LOX-1), that are predictive of the resorptive activity of mature osteoclasts. The expression of differentially expressed G-protein coupled receptors was strong during osteoclast differentiation, and these receptors are associated with bone mineral density SNPs, suggesting that they play a pivotal role in osteoclast differentiation and activity. The regulatory effects of three differentially expressed G-protein coupled receptors were exemplified by in vitro pharmacological modulation of complement 5 A receptor 1 (C5AR1), somatostatin receptor 2 (SSTR2), and free fatty acid receptor 4 (FFAR4/GPR120). Activating C5AR1 enhanced osteoclast formation, while activating SSTR2 decreased the resorptive activity of mature osteoclasts, and activating FFAR4 decreased both the number and resorptive activity of mature osteoclasts. In conclusion, we report the occurrence of transcriptional reprogramming during human osteoclast differentiation and identified SSTR2 and FFAR4 as antiresorptive G-protein coupled receptors and FLNB and LOX-1 as potential molecular markers of osteoclast activity. These data can help future investigations identify molecular regulators of osteoclast differentiation and activity and provide the basis for novel antiosteoporotic targets.
Mechanical stiffness promotes skin fibrosis via Piezo1-Wnt2/Wnt11-CCL24 positive feedback loop
Authors: He Jiahao , Cheng Xinwei , Fang Bin , Shan Shengzhou , Li Qingfeng 
Published: January 2024

AbstractSkin fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM) caused by fibrotic disorders of the skin. In recent years, ECM stiffness has emerged as a prominent mechanical cue that precedes skin fibrosis and drives its progression by promoting fibroblasts activation. However, how stiffness influences fibroblasts activation for skin fibrosis progression remains unknown. Here, we report a positive feedback loop mediated by the mechanosensitive ion channel Piezo1 and aberrant tissue mechanics in driving skin fibrosis. Piezo1 is upregulated in fibrotic skin in both humans and mice. Piezo1 knockdown dermal fibroblasts lose their fibroproliferative phenotypes despite being grown on a stiffer substrate. We show that Piezo1 acts through the Wnt2/Wnt11 pathway to mechanically induce secretion of C-C motif chemokine ligand 24 (CCL24, also known as eotaxin-2), a potent cytokine associated with fibrotic disorders. Importantly, adeno-associated virus (AAV)-mediated Piezo1 knockdown ameliorated the progression of skin fibrosis and skin stiffness in mice. Overall, increased matrix stiffness promotes skin fibrosis through the inflammatory Piezo1-Wnt2/Wnt11-CCL24 pathway. In turn, a stiffer skin microenvironment increases Piezo1 expression to exacerbate skin fibrosis aggression. Therefore, targeting Piezo1 represents a strategy to break the positive feedback loop between fibroblasts mechanotransduction and aberrant tissue mechanics in skin fibrosis.
Towards near-term quantum simulation of materials
Authors: Clinton Laura , Cubitt Toby , Flynn Brian , Gambetta Filippo Maria , Klassen Joel , Montanaro Ashley , Piddock Stephen , Santos Raul A. , Sheridan Evan 
Published: January 2024

AbstractDetermining the ground and excited state properties of materials is considered one of the most promising applications of quantum computers. On near-term hardware, the limiting constraint on such simulations is the requisite circuit depths and qubit numbers, which currently lie well beyond near-term capabilities. Here we develop a quantum algorithm which reduces the estimated cost of material simulations. For example, we obtain a circuit depth improvement by up to 6 orders of magnitude for a Trotter layer of time-dynamics simulation in the transition-metal oxide SrVO3compared with the best previous quantum algorithms. We achieve this by introducing a collection of connected techniques, including highly localised and physically compact representations of materials Hamiltonians in the Wannier basis, a hybrid fermion-to-qubit mapping, and an efficient circuit compiler. Combined together, these methods leverage locality of materials Hamiltonians and result in a design that generates quantum circuits with depth independent of the system’s size. Although the requisite resources for the quantum simulation of materials are still beyond current hardware, our results show that realistic simulation of specific properties may be feasible without necessarily requiring fully scalable, fault-tolerant quantum computers, providing quantum algorithm design incorporates deeper understanding of the target materials and applications.
Natural reversion promotes LPS elongation in an attenuated Coxiella burnetii strain
Authors: Long Carrie M. , Beare Paul A. , Cockrell Diane , Binette Picabo , Tesfamariam Mahelat , Richards Crystal , Anderson Matthew , McCormick-Ell Jessica , Brose Megan , Anderson Rebecca , Omsland Anders , Pearson Talima , Heinzen Robert A. 
Published: January 2024

AbstractLipopolysaccharide (LPS) phase variation is a critical aspect of virulence in many Gram-negative bacteria. It is of particular importance to Coxiella burnetii, the biothreat pathogen that causes Q fever, as in vitro propagation of this organism leads to LPS truncation, which is associated with an attenuated and exempted from select agent status (Nine Mile II, NMII). Here, we demonstrate that NMII was recovered from the spleens of infected guinea pigs. Moreover, these strains exhibit a previously unrecognized form of elongated LPS and display increased virulence in comparison with the initial NMII strain. The reversion of a 3-bp mutation in the gene cbu0533 directly leads to LPS elongation. To address potential safety concerns, we introduce a modified NMII strain unable to produce elongated LPS.
DNA mechanocapsules for programmable piconewton responsive drug delivery
Authors: Velusamy Arventh , Sharma Radhika , Rashid Sk Aysha , Ogasawara Hiroaki , Salaita Khalid 
Published: January 2024

AbstractThe mechanical dysregulation of cells is associated with a number of disease states, that spans from fibrosis to tumorigenesis. Hence, it is highly desirable to develop strategies to deliver drugs based on the “mechanical phenotype” of a cell. To achieve this goal, we report the development of DNA mechanocapsules (DMC) comprised of DNA tetrahedrons that are force responsive. Modeling shows the trajectory of force-induced DMC rupture and predicts how applied force spatial position and orientation tunes the force-response threshold. DMCs functionalized with adhesion ligands mechanically denature in vitro as a result of cell receptor forces. DMCs are designed to encapsulate macromolecular cargos such as dextran and oligonucleotide drugs with minimal cargo leakage and high nuclease resistance. Force-induced release and uptake of DMC cargo is validated using flow cytometry. Finally, we demonstrate force-induced mRNA knockdown of HIF-1α in a manner that is dependent on the magnitude of cellular traction forces. These results show that DMCs can be effectively used to target biophysical phenotypes which may find useful applications in immunology and cancer biology.
Alkali metal bilayer intercalation in graphene
Authors: Lin Yung-Chang , Matsumoto Rika , Liu Qiunan , Solís-Fernández Pablo , Siao Ming-Deng , Chiu Po-Wen , Ago Hiroki , Suenaga Kazu 
Published: January 2024

AbstractAlkali metal (AM) intercalation between graphene layers holds promise for electronic manipulation and energy storage, yet the underlying mechanism remains challenging to fully comprehend despite extensive research. In this study, we employ low-voltage scanning transmission electron microscopy (LV-STEM) to visualize the atomic structure of intercalated AMs (potassium, rubidium, and cesium) in bilayer graphene (BLG). Our findings reveal that the intercalated AMs adopt bilayer structures with hcp stacking, and specifically a C6M2C6 composition. These structures closely resemble the bilayer form of fcc (111) structure observed in AMs under high-pressure conditions. A negative charge transferred from bilayer AMs to graphene layers of approximately 1~1.5×1014 e−/cm−2 was determined by electron energy loss spectroscopy (EELS), Raman, and electrical transport. The bilayer AM is stable in BLG and graphite superficial layers but absent in the graphite interior, primarily dominated by single-layer AM intercalation. This hints at enhancing AM intercalation capacity by thinning the graphite material.
Salinity causes widespread restriction of methane emissions from small inland waters
Authors: Soued Cynthia , Bogard Matthew J. , Finlay Kerri , Bortolotti Lauren E. , Leavitt Peter R. , Badiou Pascal , Knox Sara H. , Jensen Sydney , Mueller Peka , Lee Sung Ching , Ng Darian , Wissel Björn , Chan Chun Ngai , Page Bryan , Kowal Paige 
Published: January 2024

AbstractInland waters are one of the largest natural sources of methane (CH4), a potent greenhouse gas, but emissions models and estimates were developed for solute-poor ecosystems and may not apply to salt-rich inland waters. Here we combine field surveys and eddy covariance measurements to show that salinity constrains microbial CH4 cycling through complex mechanisms, restricting aquatic emissions from one of the largest global hardwater regions (the Canadian Prairies). Existing models overestimated CH4 emissions from ponds and wetlands by up to several orders of magnitude, with discrepancies linked to salinity. While not significant for rivers and larger lakes, salinity interacted with organic matter availability to shape CH4 patterns in small lentic habitats. We estimate that excluding salinity leads to overestimation of emissions from small Canadian Prairie waterbodies by at least 81% ( ~ 1 Tg yr−1 CO2 equivalent), a quantity comparable to other major national emissions sources. Our findings are consistent with patterns in other hardwater landscapes, likely leading to an overestimation of global lentic CH4 emissions. Widespread salinization of inland waters may impact CH4 cycling and should be considered in future projections of aquatic emissions.
Ultrafast hot-carrier dynamics in ultrathin monocrystalline gold
Authors: Karaman Can O. , Bykov Anton Yu. , Kiani Fatemeh , Tagliabue Giulia , Zayats Anatoly V. 
Published: January 2024

AbstractApplications in photodetection, photochemistry, and active metamaterials and metasurfaces require fundamental understanding of ultrafast nonthermal and thermal electron processes in metallic nanosystems. Significant progress has been recently achieved in synthesis and investigation of low-loss monocrystalline gold, opening up opportunities for its use in ultrathin nanophotonic architectures. Here, we reveal fundamental differences in hot-electron thermalisation dynamics between monocrystalline and polycrystalline ultrathin (down to 10 nm thickness) gold films. Comparison of weak and strong excitation regimes showcases a counterintuitive unique interplay between thermalised and non-thermalised electron dynamics in mesoscopic gold with the important influence of the X-point interband transitions on the intraband electron relaxation. We also experimentally demonstrate the effect of hot-electron transfer into a substrate and the substrate thermal properties on electron-electron and electron-phonon scattering in ultrathin films. The hot-electron injection efficiency from monocrystalline gold into TiO2, approaching 9% is measured, close to the theoretical limit. These experimental and modelling results reveal the important role of crystallinity and interfaces on the microscopic electronic processes important in numerous applications.
Tumour-retained activated CCR7+ dendritic cells are heterogeneous and regulate local anti-tumour cytolytic activity
Authors: Lee Colin Y. C. , Kennedy Bethany C. , Richoz Nathan , Dean Isaac , Tuong Zewen K. , Gaspal Fabrina , Li Zhi , Willis Claire , Hasegawa Tetsuo , Whiteside Sarah K. , Posner David A. , Carlesso Gianluca , Hammond Scott A. , Dovedi Simon J. , Roychoudhuri Rahul , Withers David R. , Clatworthy Menna R. 
Published: January 2024

AbstractTumour dendritic cells (DCs) internalise antigen and upregulate CCR7, which directs their migration to tumour-draining lymph nodes (dLN). CCR7 expression is coupled to an activation programme enriched in regulatory molecule expression, including PD-L1. However, the spatio-temporal dynamics of CCR7+ DCs in anti-tumour immune responses remain unclear. Here, we use photoconvertible mice to precisely track DC migration. We report that CCR7+ DCs are the dominant DC population that migrate to the dLN, but a subset remains tumour-resident despite CCR7 expression. These tumour-retained CCR7+ DCs are phenotypically and transcriptionally distinct from their dLN counterparts and heterogeneous. Moreover, they progressively downregulate the expression of antigen presentation and pro-inflammatory transcripts with more prolonged tumour dwell-time. Tumour-residing CCR7+ DCs co-localise with PD-1+CD8+ T cells in human and murine solid tumours, and following anti-PD-L1 treatment, upregulate stimulatory molecules including OX40L, thereby augmenting anti-tumour cytolytic activity. Altogether, these data uncover previously unappreciated heterogeneity in CCR7+ DCs that may underpin a variable capacity to support intratumoural cytotoxic T cells.
Rapid functional impairment of natural killer cells following tumor entry limits anti-tumor immunity
Authors: Dean Isaac , Lee Colin Y. C. , Tuong Zewen K. , Li Zhi , Tibbitt Christopher A. , Willis Claire , Gaspal Fabrina , Kennedy Bethany C. , Matei-Rascu Veronika , Fiancette Rémi , Nordenvall Caroline , Lindforss Ulrik , Baker Syed Murtuza , Stockmann Christian , Sexl Veronika , Hammond Scott A. , Dovedi Simon J. , Mjösberg Jenny , Hepworth Matthew R. , Carlesso Gianluca , Clatworthy Menna R. , Withers David R. 
Published: January 2024

AbstractImmune cell dysfunction within the tumor microenvironment (TME) undermines the control of cancer progression. Established tumors contain phenotypically distinct, tumor-specific natural killer (NK) cells; however, the temporal dynamics, mechanistic underpinning and functional significance of the NK cell compartment remains incompletely understood. Here, we use photo-labeling, combined with longitudinal transcriptomic and cellular analyses, to interrogate the fate of intratumoral NK cells. We reveal that NK cells rapidly lose effector functions and adopt a distinct phenotypic state with features associated with tissue residency. NK cell depletion from established tumors did not alter tumor growth, indicating that intratumoral NK cells cease to actively contribute to anti-tumor responses. IL-15 administration prevented loss of function and improved tumor control, generating intratumoral NK cells with both tissue-residency characteristics and enhanced effector function. Collectively, our data reveals the fate of NK cells after recruitment into tumors and provides insight into how their function may be revived.
Magnon thermal Hall effect via emergent SU(3) flux on the antiferromagnetic skyrmion lattice
Authors: Takeda Hikaru , Kawano Masataka , Tamura Kyo , Akazawa Masatoshi , Yan Jian , Waki Takeshi , Nakamura Hiroyuki , Sato Kazuki , Narumi Yasuo , Hagiwara Masayuki , Yamashita Minoru , Hotta Chisa 
Published: January 2024

AbstractComplexity of quantum phases of matter is often understood theoretically by using gauge structures, as is recognized by the $${{\mathbb{Z}}}_{2}$$

Z

2

and U(1) gauge theory description of spin liquids in frustrated magnets. Anomalous Hall effect of conducting electrons can intrinsically arise from a U(1) gauge expressing the spatial modulation of ferromagnetic moments or from an SU(2) gauge representing the spin-orbit coupling effect. Similarly, in insulating ferro and antiferromagnets, the magnon contribution to anomalous transports is explained in terms of U(1) and SU(2) fluxes present in the ordered magnetic structure. Here, we report thermal Hall measurements of MnSc2S4 in an applied field up to 14 T, for which we consider an emergent higher rank SU(3) flux, controlling the magnon transport. The thermal Hall coefficient takes a substantial value when the material enters a three-sublattice antiferromagnetic skyrmion phase, which is in agreement with the linear spin-wave theory. In our description, magnons are dressed with SU(3) gauge field, which is a mixture of three species of U(1) gauge fields originating from the slowly varying magnetic moments on these sublattices.
Archaean continental crust formed from mafic cumulates
Authors: Smit Matthijs A. , Musiyachenko Kira A. , Goumans Jeroen 
Published: January 2024

AbstractLarge swaths of juvenile crust with tonalite-trondhjemite-granodiorite (TTG) composition were added to the continental crust from about 3.5 billion years ago. Although TTG magmatism marked a pivotal step in early crustal growth and cratonisation, the petrogenetic processes, tectonic setting and sources of TTGs are not well known. Here, we investigate the composition and petrogenesis of Archaean TTGs using high field-strength-element systematics. The Nb concentrations and Ti anomalies of TTGs show the overwhelming effects of amphibole and plagioclase fractionation and permit constraints on the composition of primary TTG melts. These melts are relatively incompatible element-poor and characterised by variably high La/Sm, Sm/Yb and Sr/Y, and positive Eu anomalies. Differences in these parameters are not indicative of melting depth, but instead track differences in the degree of melting and fractional crystallisation. Primary TTGs formed by the melting of rutile- and garnet-bearing plagioclase-cumulate rocks that resided in proto-continental roots. The partial melting of these rocks is part of a causal chain that links TTG magmatism to the formation of sanukitoids and K-rich granites. Together, these processes explain the growth and differentiation of the continental crust during the Archaean without requiring external forcing such as meteorite impact or the start of global plate tectonics.
Methionine aminopeptidase 2 and its autoproteolysis product have different binding sites on the ribosome
Authors: Klein Marius A. , Wild Klemens , Kišonaitė Miglė , Sinning Irmgard 
Published: January 2024

AbstractExcision of the initiator methionine is among the first co-translational processes that occur at the ribosome. While this crucial step in protein maturation is executed by two types of methionine aminopeptidases in eukaryotes (MAP1 and MAP2), additional roles in disease and translational regulation have drawn more attention to MAP2. Here, we report several cryo-EM structures of human and fungal MAP2 at the 80S ribosome. Irrespective of nascent chains, MAP2 can occupy the tunnel exit. On nascent chain displaying ribosomes, the MAP2-80S interaction is highly dynamic and the MAP2-specific N-terminal extension engages in stabilizing interactions with the long rRNA expansion segment ES27L. Loss of this extension by autoproteolytic cleavage impedes interactions at the tunnel, while promoting MAP2 to enter the ribosomal A-site, where it engages with crucial functional centers of translation. These findings reveal that proteolytic remodeling of MAP2 severely affects ribosome binding, and set the stage for targeted functional studies.
Subfield-specific interneuron circuits govern the hippocampal response to novelty in male mice
Authors: Hainmueller Thomas , Cazala Aurore , Huang Li-Wen , Bartos Marlene 
Published: January 2024

AbstractThe hippocampus is the brain’s center for episodic memories. Its subregions, the dentate gyrus and CA1-3, are differentially involved in memory encoding and recall. Hippocampal principal cells represent episodic features like movement, space, and context, but less is known about GABAergic interneurons. Here, we performed two-photon calcium imaging of parvalbumin- and somatostatin-expressing interneurons in the dentate gyrus and CA1-3 of male mice exploring virtual environments. Parvalbumin-interneurons increased activity with running-speed and reduced it in novel environments. Somatostatin-interneurons in CA1-3 behaved similar to parvalbumin-expressing cells, but their dentate gyrus counterparts increased activity during rest and in novel environments. Congruently, chemogenetic silencing of dentate parvalbumin-interneurons had prominent effects in familiar contexts, while silencing somatostatin-expressing cells increased similarity of granule cell representations between novel and familiar environments. Our data indicate unique roles for parvalbumin- and somatostatin-positive interneurons in the dentate gyrus that are distinct from those in CA1-3 and may support routing of novel information.
Creating amphiphilic porosity in two-dimensional covalent organic frameworks via steric-hindrance-mediated precision hydrophilic-hydrophobic microphase separation
Authors: Jiang Shu-Yan , Zhou Zhi-Bei , Gan Shi-Xian , Lu Ya , Liu Chao , Qi Qiao-Yan , Yao Jin , Zhao Xin 
Published: January 2024

AbstractCreating different pore environments within a covalent organic framework (COF) will lead to useful multicompartment structure and multiple functions, which however has been scarcely achieved. Herein we report designed synthesis of three two-dimensional COFs with amphiphilic porosity by steric-hindrance-mediated precision hydrophilic-hydrophobic microphase separation. Dictated by the different steric effect of the substituents introduced to a monomer, dual-pore COFs with kgm net, in which all hydroxyls locate in trigonal micropores while hydrophobic sidechains exclusively distribute in hexagonal mesopores, have been constructed to form completely separated hydrophilic and hydrophobic nanochannels. The unique amphiphilic channels in the COFs enable the formation of Janus membranes via interface growth. This work has realized the creation of two types of channels with opposite properties in one COF, demonstrating the feasibility of introducing different properties/functions into different pores of heteropore COFs, which can be a useful strategy to develop multifunctional materials.