bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tuning of oscillation modes by controlling dimensionality of spin structures
Authors: Han Hee-Sung , Lee Sooseok , Jung Min-Seung , Kim Namkyu , Jung Dae-Han , Kang Myeonghwan , Ok Hye-Jin , Chao Weilun , Yu Young-Sang , Hong Jung-Il , Im Mi-Young , Lee Ki‐Suk 
Published: November 2022

AbstractHarmonic oscillation of spin structures is a physical phenomenon that offers great potential for applications in nanotechnologies such as nano-oscillators and bio-inspired computing. The effective tuning of oscillations over wide frequency ranges within a single ferromagnetic nanoelement is a prerequisite to realize oscillation-based nanodevices, but it has not been addressed experimentally or theoretically. Here, utilizing a vortex core structure, one of spin structures, we report a drastic change of oscillation modes over the frequency range from MHz to sub-GHz in a 100 nm-thick permalloy circular disk. Oscillation mode was found to considerably depend on the shape and dimension of the vortex core structure and various oscillation modes over a wide range of frequencies appeared with dimensional change in the vortex core structure. This work demonstrates that oscillation modes of the vortex core structure can be effectively tuned and opens a way to apply spin structures to oscillation-based technology.
Rigidity-dependent formation process of DNA supramolecular hydrogels
Authors: Pan Yufan , Yang Bo , Xu Rui , Li Xin , Dong Yuanchen , Liu Dongsheng 
Published: November 2022

AbstractA DNA building block with tunable rigidity was constructed, and the corresponding hydrogel formation process was investigated accordingly. A high rigidity was demonstrated to facilitate fast gelation. Different gelation pathways of the rigid and flexible building blocks were revealed, and a cyclized dimer intermediate was proposed. The energy barrier of the ring-opening process was also shown to play a fundamental role in determining the gelation kinetics. Furthermore, the hydrogel molecular network rigidity was also tuned in situ through strand displacement, which also supports the kinetic control mechanism of the formation process of DNA hydrogels.
AMPK induces degradation of the transcriptional repressor PROX1 impairing branched amino acid metabolism and tumourigenesis
Authors: Wang Yanan , Luo Mengjun , Wang Fan , Tong Yu , Li Linfeng , Shu Yu , Qiao Ke , Zhang Lei , Yan Guoquan , Liu Jing , Ji Hongbin , Xie Youhua , Zhang Yonglong , Gao Wei-Qiang , Liu Yanfeng 
Published: November 2022

AbstractTumour cell metabolic plasticity is essential for tumour progression and therapeutic responses, yet the underlying mechanisms remain poorly understood. Here, we identify Prospero-related homeobox 1 (PROX1) as a crucial factor for tumour metabolic plasticity. Notably, PROX1 is reduced by glucose starvation or AMP-activated protein kinase (AMPK) activation and is elevated in liver kinase B1 (LKB1)-deficient tumours. Furthermore, the Ser79 phosphorylation of PROX1 by AMPK enhances the recruitment of CUL4-DDB1 ubiquitin ligase to promote PROX1 degradation. Downregulation of PROX1 activates branched-chain amino acids (BCAA) degradation through mediating epigenetic modifications and inhibits mammalian target-of-rapamycin (mTOR) signalling. Importantly, PROX1 deficiency or Ser79 phosphorylation in liver tumour shows therapeutic resistance to metformin. Clinically, the AMPK-PROX1 axis in human cancers is important for patient clinical outcomes. Collectively, our results demonstrate that deficiency of the LKB1-AMPK axis in cancers reactivates PROX1 to sustain intracellular BCAA pools, resulting in enhanced mTOR signalling, and facilitating tumourigenesis and aggressiveness.
Giant switchable non thermally-activated conduction in 180° domain walls in tetragonal Pb(Zr,Ti)O3
Authors: Risch Felix , Tikhonov Yuri , Lukyanchuk Igor , Ionescu Adrian M. , Stolichnov Igor 
Published: November 2022

AbstractConductive domain walls in ferroelectrics offer a promising concept of nanoelectronic circuits with 2D domain-wall channels playing roles of memristors or synoptic interconnections. However, domain wall conduction remains challenging to control and pA-range currents typically measured on individual walls are too low for single-channel devices. Charged domain walls show higher conductivity, but are generally unstable and difficult to create. Here, we show highly conductive and stable channels on ubiquitous 180° domain walls in the archetypical ferroelectric, tetragonal Pb(Zr,Ti)O3. These electrically erasable/rewritable channels show currents of tens of nanoamperes (200 to 400 nA/μm) at voltages ≤2 V and metallic-like non thermally-activated transport properties down to 4 K, as confirmed by nanoscopic mapping. The domain structure analysis and phase-field simulations reveal complex switching dynamics, in which the extraordinary conductivity in strained Pb(Zr,Ti)O3 films is explained by an interplay between ferroelastic a- and c-domains. This work demonstrates the potential of accessible and stable arrangements of nominally uncharged and electrically switchable domain walls for nanoelectronics.
Sound velocity of hexagonal close-packed iron to the Earth’s inner core pressure
Authors: Ikuta Daijo , Ohtani Eiji , Fukui Hiroshi , Sakai Takeshi , Ishikawa Daisuke , Baron Alfred Q. R. 
Published: November 2022

AbstractHere we determine the compressional and shear wave velocities (vp and vs) of hexagonal close-packed iron, a candidate for the main constituent of the Earth’s inner core, to pressures above 300 gigapascals using a newly designed diamond anvil cell and inelastic X-ray scattering combined with X-ray diffraction. The present results reveal that the vp and vs of the Preliminary reference Earth model (PREM) inner core are 4(±2)% and 36(±17)% slower than those of the pure iron, respectively at the centre of the core. The density and sound velocity of the PREM inner core can be explained by addition of 3(±1) wt% silicon and 3(±2) wt% sulphur to iron‒5 wt% nickel alloy. Our suggested inner core composition is consistent with the existing outer core model with oxygen, as the growth of the inner core may have created a secular enrichment of the element in the outer core.
Growth of ocean thermal energy conversion resources under greenhouse warming regulated by oceanic eddies
Authors: Du Tianshi , Jing Zhao , Wu Lixin , Wang Hong , Chen Zhaohui , Ma Xiaohui , Gan Bolan , Yang Haiyuan 
Published: November 2022

AbstractThe concept of utilizing a large temperature difference (>20 °C) between the surface and deep seawater to generate electricity, known as the ocean thermal energy conversion (OTEC), provides a renewable solution to fueling our future. However, it remains poorly assessed how the OTEC resources will respond to future climate change. Here, we find that the global OTEC power potential is projected to increase by 46% around the end of this century under a high carbon emission scenario, compared to its present-day level. The augmented OTEC power potential due to the rising sea surface temperature is partially offset by the deep ocean warming. The offsetting effect is more evident in the Atlantic Ocean than Pacific and Indian Oceans. This is mainly attributed to the weakening of mesoscale eddy-induced upward heat transport, suggesting an important role of mesoscale eddies in regulating the response of thermal stratification and OTEC power potential to greenhouse warming.
Reduced secretion of neuronal growth regulator 1 contributes to impaired adipose-neuronal crosstalk in obesity
Authors: Duregotti Elisa , Reumiller Christina M. , Mayr Ursula , Hasman Maria , Schmidt Lukas E. , Burnap Sean A. , Theofilatos Konstantinos , Barallobre-Barreiro Javier , Beran Arne , Grandoch Maria , Viviano Alessandro , Jahangiri Marjan , Mayr Manuel 
Published: November 2022

AbstractWhile the endocrine function of white adipose tissue has been extensively explored, comparatively little is known about the secretory activity of less-investigated fat depots. Here, we use proteomics to compare the secretory profiles of male murine perivascular depots with those of canonical white and brown fat. Perivascular secretomes show enrichment for neuronal cell-adhesion molecules, reflecting a higher content of intra-parenchymal sympathetic projections compared to other adipose depots. The sympathetic innervation is reduced in the perivascular fat of obese (ob/ob) male mice, as well as in the epicardial fat of patients with obesity. Degeneration of sympathetic neurites is observed in presence of conditioned media of fat explants from ob/ob mice, that show reduced secretion of neuronal growth regulator 1. Supplementation of neuronal growth regulator 1 reverses this neurodegenerative effect, unveiling a neurotrophic role for this protein previously identified as a locus associated with human obesity. As sympathetic stimulation triggers energy-consuming processes in adipose tissue, an impaired adipose-neuronal crosstalk is likely to contribute to the disrupted metabolic homeostasis characterising obesity.
Multidimensional hyperspin machine
Authors: Calvanese Strinati Marcello , Conti Claudio 
Published: November 2022

AbstractFrom condensed matter to quantum chromodynamics, multidimensional spins are a fundamental paradigm, with a pivotal role in combinatorial optimization and machine learning. Machines formed by coupled parametric oscillators can simulate spin models, but only for Ising or low-dimensional spins. Currently, machines implementing arbitrary dimensions remain a challenge. Here, we introduce and validate a hyperspin machine to simulate multidimensional continuous spin models. We realize high-dimensional spins by pumping groups of parametric oscillators, and show that the hyperspin machine finds to a very good approximation the ground state of complex graphs. The hyperspin machine can interpolate between different dimensions by tuning the coupling topology, a strategy that we call “dimensional annealing”. When interpolating between the XY and the Ising model, the dimensional annealing substantially increases the success probability compared to conventional Ising simulators. Hyperspin machines are a new computational model for combinatorial optimization. They can be realized by off-the-shelf hardware for ultrafast, large-scale applications in classical and quantum computing, condensed-matter physics, and fundamental studies.
Postnatal expansion of mesenteric lymph node stromal cells towards reticular and CD34+ stromal cell subsets
Authors: Pezoldt Joern , Wiechers Carolin , Zou Mangge , Litovchenko Maria , Biocanin Marjan , Beckstette Michael , Sitnik Katarzyna , Palatella Martina , van Mierlo Guido , Chen Wanze , Gardeux Vincent , Floess Stefan , Ebel Maria , Russeil Julie , Arampatzi Panagiota , Vafardanejad Ehsan , Saliba Antoine-Emmanuel , Deplancke Bart , Huehn Jochen 
Published: November 2022

AbstractGut-draining mesenteric lymph nodes (LN) provide the framework to shape intestinal adaptive immune responses. Based on the transcriptional signatures established by our previous work, the composition and immunomodulatory function of LN stromal cells (SC) vary according to location. Here, we describe the single-cell composition and development of the SC compartment within mesenteric LNs derived from postnatal to aged mice. We identify CD34+SC and fibroblastic reticular stromal cell (FRC) progenitors as putative progenitors, both supplying the typical rapid postnatal mesenteric LN expansion. We further establish the location-specific chromatin accessibility and DNA methylation landscape of non-endothelial SCs and identify a microbiota-independent core epigenomic signature, showing characteristic differences between SCs from mesenteric and skin-draining peripheral LNs. The epigenomic landscape of SCs points to dynamic expression of Irf3 along the differentiation trajectories of FRCs. Accordingly, a mesenchymal stem cell line acquires a Cxcl9+FRC molecular phenotype upon lentiviral overexpression of Irf3, and the relevance of Irf3 for SC biology is further underscored by the diminished proportion of Ccl19+and Cxcl9+FRCs in LNs of Irf3-/-mice. Together, our data constitute a comprehensive transcriptional and epigenomic map of mesenteric LNSC development in early life and dissect location-specific, microbiota-independent properties of non-endothelial SCs.
A single-cell analysis reveals tumor heterogeneity and immune environment of acral melanoma
Authors: Zhang Chao , Shen Hongru , Yang Tielong , Li Ting , Liu Xinyue , Wang Jin , Liao Zhichao , Wei Junqiang , Lu Jia , Liu Haotian , Xiang Lijie , Yang Yichen , Yang Meng , Wang Duan , Li Yang , Xing Ruwei , Teng Sheng , Zhao Jun , Yang Yun , Zhao Gang , Chen Kexin , Li Xiangchun , Yang Jilong 
Published: November 2022

AbstractAcral melanoma is a dismal subtype of melanoma occurring in glabrous acral skin, and has a higher incidence in East Asians. We perform single-cell RNA sequencing for 63,394 cells obtained from 5 acral and 3 cutaneous melanoma samples to investigate tumor heterogeneity and immune environment. We define 5 orthogonal functional cell clusters that are involved in TGF-beta signaling, Type I interferon, Wnt signaling, Cell cycle, and Cholesterol efflux signaling. Signatures of enriched TGF-beta, Type I interferon, and cholesterol efflux signaling are significantly associated with good prognosis of melanoma. Compared with cutaneous melanoma, acral melanoma samples have significantly severe immunosuppressive state including depletion of cytotoxic CD8+ T cells, enrichment of Treg cells, and exhausted CD8+ T cells. PD1 and TIM-3 have higher expression in the exhaustive CD8+ T cells of acral melanoma. Key findings are verified in two independent validation sets. This study contributes to our better understanding of acral melanoma.
Defective activation and regulation of type I interferon immunity is associated with increasing COVID-19 severity
Authors: Smith Nikaïa , Possémé Céline , Bondet Vincent , Sugrue Jamie , Townsend Liam , Charbit Bruno , Rouilly Vincent , Saint-André Violaine , Dott Tom , Pozo Andre Rodriguez , Yatim Nader , Schwartz Olivier , Cervantes-Gonzalez Minerva , Ghosn Jade , Bastard Paul , Casanova Jean Laurent , Szwebel Tali-Anne , Terrier Benjamin , Conlon Niall , O’Farrelly Cliona , Cheallaigh Clíona Ní , Bourke Nollaig M. , Duffy Darragh 
Published: November 2022

AbstractHost immunity to infection with SARS-CoV-2 is highly variable, dictating diverse clinical outcomes ranging from asymptomatic to severe disease and death. We previously reported reduced type I interferon in severe COVID-19 patients preceded clinical worsening. Further studies identified genetic mutations in loci of the TLR3- or TLR7-dependent interferon-I pathways, or neutralizing interferon-I autoantibodies as risk factors for development of COVID-19 pneumonia. Here we show in patient cohorts with different severities of COVID-19, that baseline plasma interferon α measures differ according to the immunoassay used, timing of sampling, the interferon α subtype measured, and the presence of autoantibodies. We also show a consistently reduced induction of interferon-I proteins in hospitalized COVID-19 patients upon immune stimulation, that is not associated with detectable neutralizing autoantibodies against interferon α or interferon ω. Intracellular proteomic analysis shows increased monocyte numbers in hospitalized COVID-19 patients but impaired interferon-I response after stimulation. We confirm this by ex vivo whole blood stimulation with interferon-I which induces transcriptomic responses associated with inflammation in hospitalized COVID-19 patients, that is not seen in controls or non-hospitalized moderate cases. These results may explain the dichotomy of the poor clinical response to interferon-I based treatments in late stage COVID-19, despite the importance of interferon-I in early acute infection and may guide alternative therapeutic strategies.
Low-dose AAV-CRISPR-mediated liver-specific knock-in restored hemostasis in neonatal hemophilia B mice with subtle antibody response
Authors: He Xiangjun , Zhang Zhenjie , Xue Junyi , Wang Yaofeng , Zhang Siqi , Wei Junkang , Zhang Chenzi , Wang Jue , Urip Brian Anugerah , Ngan Chun Christopher , Sun Junjiang , Li Yuefeng , Lu Zhiqian , Zhao Hui , Pei Duanqing , Li Chi-Kong , Feng Bo 
Published: November 2022

AbstractAAV-delivered CRISPR/Cas9 (AAV-CRISPR) has shown promising potentials in preclinical models to efficiently insert therapeutic gene sequences in somatic tissues. However, the AAV input doses required were prohibitively high and posed serious risk of toxicity. Here, we performed AAV-CRISPR mediated homology-independent knock-in at a new target site in mAlb 3’UTR and demonstrated that single dose of AAVs enabled long-term integration and expression of hF9 transgene in both adult and neonatal hemophilia B mice (mF9 −/−), yielding high levels of circulating human Factor IX (hFIX) and stable hemostasis restoration during entire 48-week observation period. Furthermore, we achieved hemostasis correction with a significantly lower AAV dose (2 × 109 vg/neonate and 1 × 1010 vg/adult mouse) through liver-specific gene knock-in using hyperactive hF9R338L variant. The plasma antibodies against Cas9 and AAV in the neonatal mice receiving low-dose AAV-CRISPR were negligible, which lent support to the development of AAV-CRISPR mediated somatic knock-in for treating inherited diseases.
A marine sponge-derived lectin reveals hidden pathway for thrombopoietin receptor activation
Authors: Watari Hiromi , Kageyama Hiromu , Masubuchi Nami , Nakajima Hiroya , Onodera Kako , Focia Pamela J. , Oshiro Takumi , Matsui Takashi , Kodera Yoshio , Ogawa Tomohisa , Yokoyama Takeshi , Hirayama Makoto , Hori Kanji , Freymann Douglas M. , Imai Misa , Komatsu Norio , Araki Marito , Tanaka Yoshikazu , Sakai Ryuichi 
Published: November 2022

AbstractN-glycan-mediated activation of the thrombopoietin receptor (MPL) under pathological conditions has been implicated in myeloproliferative neoplasms induced by mutant calreticulin, which forms an endogenous receptor-agonist complex that traffics to the cell surface and constitutively activates the receptor. However, the molecular basis for this mechanism is elusive because oncogenic activation occurs only in the cell-intrinsic complex and is thus cannot be replicated with external agonists. Here, we describe the structure and function of a marine sponge-derived MPL agonist, thrombocorticin (ThC), a homodimerized lectin with calcium-dependent fucose-binding properties. In-depth characterization of lectin-induced activation showed that, similar to oncogenic activation, sugar chain-mediated activation persists due to limited receptor internalization. The strong synergy between ThC and thrombopoietin suggests that ThC catalyzes the formation of receptor dimers on the cell surface. Overall, the existence of sugar-mediated MPL activation, in which the mode of activation is different from the original ligand, suggests that receptor activation is unpredictably diverse in living organisms.
Critical Offset Magnetic PArticle SpectroScopy for rapid and highly sensitive medical point-of-care diagnostics
Authors: Vogel Patrick , Rückert Martin Andreas , Friedrich Bernhard , Tietze Rainer , Lyer Stefan , Kampf Thomas , Hennig Thomas , Dölken Lars , Alexiou Christoph , Behr Volker Christian 
Published: November 2022

AbstractMagnetic nanoparticles (MNPs) have been adapted for many applications, e.g., bioassays for the detection of biomarkers such as antibodies, by controlled engineering of specific surface properties. Specific measurement of such binding states is of high interest but currently limited to highly sensitive techniques such as ELISA or flow cytometry, which are relatively inflexible, difficult to handle, expensive and time-consuming. Here we report a method named COMPASS (Critical-Offset-Magnetic-Particle-SpectroScopy), which is based on a critical offset magnetic field, enabling sensitive detection to minimal changes in mobility of MNP ensembles, e.g., resulting from SARS-CoV-2 antibodies binding to the S antigen on the surface of functionalized MNPs. With a sensitivity of 0.33 fmole/50 µl (≙7 pM) for SARS-CoV-2-S1 antibodies, measured with a low-cost portable COMPASS device, the proposed technique is competitive with respect to sensitivity while providing flexibility, robustness, and a measurement time of seconds per sample. In addition, initial results with blood serum demonstrate high specificity.
GPSM1 impairs metabolic homeostasis by controlling a pro-inflammatory pathway in macrophages
Authors: Yan Jing , Zhang Yuemei , Yu Hairong , Zong Yicen , Wang Daixi , Zheng Jiangfei , Jin Li , Yu Xiangtian , Liu Caizhi , Zhang Yi , Jiang Feng , Zhang Rong , Fang Xiangnan , Xu Ting , Li Mingyu , Di Jianzhong , Lu Yan , Ma Xinran , Zhang Jian , Jia Weiping , Hu Cheng 
Published: November 2022

AbstractG-protein-signaling modulator 1 (GPSM1) exhibits strong genetic association with Type 2 diabetes (T2D) and Body Mass Index in population studies. However, how GPSM1 carries out such control and in which types of cells are poorly understood. Here, we demonstrate that myeloid GPSM1 promotes metabolic inflammation to accelerate T2D and obesity development. Mice with myeloid-specific GPSM1 ablation are protected against high fat diet-induced insulin resistance, glucose dysregulation, and liver steatosis via repression of adipose tissue pro-inflammatory states. Mechanistically, GPSM1 deficiency mainly promotes TNFAIP3 transcription via the Gαi3/cAMP/PKA/CREB axis, thus inhibiting TLR4-induced NF-κB signaling in macrophages. In addition, we identify a small-molecule compound, AN-465/42243987, which suppresses the pro-inflammatory phenotype by inhibiting GPSM1 function, which could make it a candidate for metabolic therapy. Furthermore, GPSM1 expression is upregulated in visceral fat of individuals with obesity and is correlated with clinical metabolic traits. Overall, our findings identify macrophage GPSM1 as a link between metabolic inflammation and systemic homeostasis.
Gating and ion selectivity of Channelrhodopsins are critical for photo-activated orientation of Chlamydomonas as shown by in vivo point mutation
Authors: Baidukova Olga , Oppermann Johannes , Kelterborn Simon , Fernandez Lahore Rodrigo G. , Schumacher Dimitri , Evers Heide , Kamrani Yousef Yari , Hegemann Peter 
Published: November 2022

AbstractThe green unicellular alga Chlamydomonas reinhardtii with two photoreceptors called channelrhodopsins is a model organism that gave birth to a new scientific field of biomedical studies, optogenetics. Although channelrhodopsins are helping to decipher the activity of the human brain, their functionality has never been extensively studied in the organism of origin, mainly due to the difficulties connected to reverse genetic interventions. In this study, we present a CRISPR-Cas9-based technique that enables a precise in vivo exchange of single amino acids in a selected gene. To shed light on the function of channelrhodopsins ChR1 (C1) and ChR2 (C2) in vivo, we deleted both channelrhodopsins independently in the wild-type strain and introduced point mutations in the remaining channel, causing modified photocycle kinetics and ion selectivity. The mutated strains, ΔC1C2-E123T, ΔC1C2-E90R and ΔC1C2-E90Q, showed about 100-fold decrease in photosensitivity, a reduced photophobic response and faster light adaptation rates due to accelerated photocycle kinetics and reduced Ca2+ conductance. Moreover, the ΔC1C2-E90Q with an additionally reduced H+ permeability produced an electrical response only in the presence of Na+ ions, highlighting a contribution and importance of H+ conductance to photocurrents in the wild-type algae. Finally, in the ΔC1C2-E90R strain with the channelrhodopsin selectivity converted to anions, no photo-responses were detected. We conclude that the precise photocycle kinetics and the particular ion selectivity of channelrhodopsins are the key parameters for efficient phototaxis in low light conditions.