bluuebunny/crossref_metadata_2025_split huggingface dataset:
Weaker connectivity in resting state networks is associated with disinhibited eating in older adults
Authors: Brennan Anthony , Marstaller Lars , Burianová Hana , Benton David , Hanley Claire J. , Newstead Simon , Young Hayley A. 
Published: January 2022

AbstractBackground/objectivesObesity affects more than forty percent of adults over the age of sixty. Aberrant eating styles such as disinhibition have been associated with the engagement of brain networks underlying executive functioning, attentional control, and interoception. However, these effects have been exclusively studied in young samples overlooking those most at risk of obesity related harm.MethodsHere we assessed associations between resting-state functional connectivity and disinhibited eating (using the Three Factor Eating Questionnaire) in twenty-one younger (aged 19–34 years, BMI range: 18–31) and twenty older (aged 60–73 years, BMI range: 19–32) adults matched for BMI. The Alternative Healthy Eating Index was used to quantify diet quality.ResultsOlder, compared to younger, individuals reported lower levels of disinhibited eating, consumed a healthier diet, and had weaker connectivity in the frontoparietal (FPN) and default mode (DMN) networks. In addition, associations between functional connectivity and eating behaviour differed between the two age groups. In older adults, disinhibited eating was associated with weaker connectivity in the FPN and DMN––effects that were absent in the younger sample. Importantly, these effects could not be explained by differences in habitual diet.ConclusionsThese findings point to a change in interoceptive signalling as part of the ageing process, which may contribute to behavioural changes in energy intake, and highlight the importance of studying this under researched population.
Blockade of beta-adrenergic receptors reduces cancer growth and enhances the response to anti-CTLA4 therapy by modulating the tumor microenvironment
Authors: Fjæstad Klaire Yixin , Rømer Anne Mette Askehøj , Goitea Victor , Johansen Astrid Zedlitz , Thorseth Marie-Louise , Carretta Marco , Engelholm Lars Henning , Grøntved Lars , Junker Niels , Madsen Daniel Hargbøl 
Published: January 2022

AbstractThe development of immune checkpoint inhibitors (ICI) marks an important breakthrough of cancer therapies in the past years. However, only a limited fraction of patients benefit from such treatments, prompting the search for immune modulating agents that can improve the therapeutic efficacy. The nonselective beta blocker, propranolol, which for decades has been prescribed for the treatment of cardiovascular conditions, has recently been used successfully to treat metastatic angiosarcoma. These results have led to an orphan drug designation by the European Medicines Agency for the treatment of soft tissue sarcomas. The anti-tumor effects of propranolol are suggested to involve the reduction of cancer cell proliferation as well as angiogenesis. Here, we show that oral administration of propranolol delays tumor progression of MCA205 fibrosarcoma model and MC38 colon cancer model and increases the survival rate of tumor bearing mice. Propranolol works by reducing tumor angiogenesis and facilitating an anti-tumoral microenvironment with increased T cell infiltration and reduced infiltration of myeloid-derived suppressor cells (MDSCs). Using T cell deficient mice, we demonstrate that the full anti-tumor effect of propranolol requires the presence of T cells. Flow cytometry-based analysis and RNA sequencing of FACS-sorted cells show that propranolol treatment leads to an upregulation of PD-L1 on tumor associated macrophages (TAMs) and changes in their chemokine expression profile. Lastly, we observe that the co-administration of propranolol significantly enhances the efficacy of anti-CTLA4 therapy. Our results identify propranolol as an immune modulating agent, which can improve immune checkpoint inhibitor therapies in soft tissue sarcoma patients and potentially in other cancers.
Linc01133 contributes to gastric cancer growth by enhancing YES1-dependent YAP1 nuclear translocation via sponging miR-145-5p
Authors: Sun Yujing , Tian Yuan , He Junyi , Tian Yaru , Zhang Guohao , Zhao Ruinan , Zhu Wen-jie , Gao Peng 
Published: January 2022

AbstractThe long intergenic non-coding RNA linc01133 is reported to be oncogenic in various malignancies. However, the role and mechanism of linc01133 in regulating gastric cancer growth is still not clear. In the present study, we found that linc01133 was significantly upregulated in gastric cancer tissues compared to non-tumorous gastric tissues. Linc01133 over-expression significantly correlated with tumor size and tumor differentiation in gastric cancer patients. The expression of linc01133 was regulated by c-Jun and c-Fos collaboratively. In both in vitro and in vivo studies, linc01133 was shown to promote gastric cancer cell growth. Linc01133 localized in the cytoplasm and functioned as an endogenous competing RNA of miR-145-5p to upregulate the expression of YES1, which was proved to be the target gene of miR-145-5p. By promoting YES1-dependent YAP1 nuclear translocation, linc01133 upregulated the expression of the key cell cycle regulators CDK4, CDK6 and cyclin D1 to promote G1-S phase transition. Thus, our study unveiled the function and mechanism of linc01133 regulating cell cycle progression in gastric cancer.
The immune-suppressive landscape in lepromatous leprosy revealed by single-cell RNA sequencing
Authors: Mi Zihao , Wang Zhenzhen , Xue Xiaotong , Liu Tingting , Wang Chuan , Sun Lele , Yu Gongqi , Zhang Yuan , Shi Peidian , Sun Yonghu , Yang Yongliang , Ma Shanshan , Wang Zhe , Yu Yueqian , Liu Jianjun , Liu Hong , Zhang Furen 
Published: January 2022

AbstractLepromatous leprosy (L-LEP), caused by the massive proliferation of Mycobacterium leprae primarily in macrophages, is an ideal disease model for investigating the molecular mechanism of intracellular bacteria evading or modulating host immune response. Here, we performed single-cell RNA sequencing of both skin biopsies and peripheral blood mononuclear cells (PBMCs) of L-LEP patients and healthy controls. In L-LEP lesions, we revealed remarkable upregulation of APOE expression that showed a negative correlation with the major histocompatibility complex II gene HLA-DQB2 and MIF, which encodes a pro-inflammatory and anti-microbial cytokine, in the subset of macrophages exhibiting a high expression level of LIPA. The exhaustion of CD8+ T cells featured by the high expression of TIGIT and LAG3 in L-LEP lesions was demonstrated. Moreover, remarkable enhancement of inhibitory immune receptors mediated crosstalk between skin immune cells was observed in L-LEP lesions. For PBMCs, a high expression level of APOE in the HLA-DRhighFBP1high monocyte subset and the expansion of regulatory T cells were found to be associated with L-LEP. These findings revealed the primary suppressive landscape in the L-LEP patients, providing potential targets for the intervention of intracellular bacteria caused persistent infections.
Gut microbiota promotes cholesterol gallstone formation by modulating bile acid composition and biliary cholesterol secretion
Authors: Hu Hai , Shao Wentao , Liu Qian , Liu Ning , Wang Qihan , Xu Jin , Zhang Xin , Weng Zhenkun , Lu Qifan , Jiao Long , Chen Chaobo , Sun Haidong , Jiang Zhaoyan , Zhang Xiaoping , Gu Aihua 
Published: January 2022

AbstractCholesterol gallstone disease is a worldwide common disease. Cholesterol supersaturation in gallbladder bile is the prerequisite for its pathogenesis, while the mechanism is not completely understood. In this study, we find enrichment of gut microbiota (especially Desulfovibrionales) in patients with gallstone disease. Fecal transplantation of gut microbiota from gallstone patients to gallstone-resistant strain of mice can induce gallstone formation. Carrying Desulfovibrionales is associated with enhanced cecal secondary bile acids production and increase of bile acid hydrophobicity facilitating intestinal cholesterol absorption. Meanwhile, the metabolic product of Desulfovibrionales, H2S increase and is shown to induce hepatic FXR and inhibit CYP7A1 expression. Mice carrying Desulfovibrionales present induction of hepatic expression of cholesterol transporters Abcg5/g8 to promote biliary secretion of cholesterol as well. Our study demonstrates the role of gut microbiota, Desulfovibrionales, as an environmental regulator contributing to gallstone formation through its influence on bile acid and cholesterol metabolism.
Preparative-scale synthesis of nonacene
Authors: Jančařík Andrej , Holec Jan , Nagata Yuuya , Šámal Michal , Gourdon Andre 
Published: January 2022

AbstractDuring the last years we have witnessed progressive evolution of preparation of acenes with length up to dodecacene by on-surface synthesis in ultra-high vacuum or generation of acenes up to decacene in solid matrices at low temperatures. While these protocols with very specific conditions produce the acenes in amount of few molecules, the strategies leading to the acenes in large quantities dawdle behind. Only recently and after 70 years of synthetic attempts, heptacene has been prepared in bulk phase. However, the preparative scale synthesis of higher homologues still remains a formidable challenge. Here we report the preparation and characterisation of nonacene and show its excellent thermal and in-time stability.
A bimodal distribution of haze in Pluto’s atmosphere
Authors: Fan Siteng , Gao Peter , Zhang Xi , Adams Danica J. , Kutsop Nicholas W. , Bierson Carver J. , Liu Chao , Yang Jiani , Young Leslie A. , Cheng Andrew F. , Yung Yuk L. 
Published: January 2022

AbstractPluto, Titan, and Triton make up a unique class of solar system bodies, with icy surfaces and chemically reducing atmospheres rich in organic photochemistry and haze formation. Hazes play important roles in these atmospheres, with physical and chemical processes highly dependent on particle sizes, but the haze size distribution in reducing atmospheres is currently poorly understood. Here we report observational evidence that Pluto’s haze particles are bimodally distributed, which successfully reproduces the full phase scattering observations from New Horizons. Combined with previous simulations of Titan’s haze, this result suggests that haze particles in reducing atmospheres undergo rapid shape change near pressure levels ~0.5 Pa and favors a photochemical rather than a dynamical origin for the formation of Titan’s detached haze. It also demonstrates that both oxidizing and reducing atmospheres can produce multi-modal hazes, and encourages reanalysis of observations of hazes on Titan and Triton.
C-type lectin receptor CLEC4A2 promotes tissue adaptation of macrophages and protects against atherosclerosis
Authors: Park Inhye , Goddard Michael E. , Cole Jennifer E. , Zanin Natacha , Lyytikäinen Leo-Pekka , Lehtimäki Terho , Andreakos Evangelos , Feldmann Marc , Udalova Irina , Drozdov Ignat , Monaco Claudia 
Published: January 2022

AbstractMacrophages are integral to the pathogenesis of atherosclerosis, but the contribution of distinct macrophage subsets to disease remains poorly defined. Using single cell technologies and conditional ablation via aLysMCre+Clec4a2flox/DTRmouse strain, we demonstrate that the expression of the C-type lectin receptor CLEC4A2 is a distinguishing feature of vascular resident macrophages endowed with athero-protective properties. Through genetic deletion and competitive bone marrow chimera experiments, we identify CLEC4A2 as an intrinsic regulator of macrophage tissue adaptation by promoting a bias in monocyte-to-macrophage in situ differentiation towards colony stimulating factor 1 (CSF1) in vascular health and disease. During atherogenesis, CLEC4A2 deficiency results in loss of resident vascular macrophages and their homeostatic properties causing dysfunctional cholesterol metabolism and enhanced toll-like receptor triggering, exacerbating disease. Our study demonstrates that CLEC4A2 licenses monocytes to join the vascular resident macrophage pool, and that CLEC4A2-mediated macrophage homeostasis is critical to combat cardiovascular disease.
MyoD is a 3D genome structure organizer for muscle cell identity
Authors: Wang Ruiting , Chen Fengling , Chen Qian , Wan Xin , Shi Minglei , Chen Antony K. , Ma Zhao , Li Guohong , Wang Min , Ying Yachen , Liu Qinyao , Li Hu , Zhang Xu , Ma Jinbiao , Zhong Jiayun , Chen Meihong , Zhang Michael Q. , Zhang Yong , Chen Yang , Zhu Dahai 
Published: January 2022

AbstractThe genome exists as an organized, three-dimensional (3D) dynamic architecture, and each cell type has a unique 3D genome organization that determines its cell identity. An unresolved question is how cell type-specific 3D genome structures are established during development. Here, we analyzed 3D genome structures in muscle cells from mice lacking the muscle lineage transcription factor (TF), MyoD, versus wild-type mice. We show that MyoD functions as a “genome organizer” that specifies 3D genome architecture unique to muscle cell development, and that H3K27ac is insufficient for the establishment of MyoD-induced chromatin loops in muscle cells. Moreover, we present evidence that other cell lineage-specific TFs might also exert functional roles in orchestrating lineage-specific 3D genome organization during development.
Robust ultrathin nanoporous MOF membrane with intra-crystalline defects for fast water transport
Authors: Wang Xueling , Lyu Qiang , Tong Tiezheng , Sun Kuo , Lin Li-Chiang , Tang Chuyang Y. , Yang Fenglin , Guiver Michael D. , Quan Xie , Dong Yingchao 
Published: January 2022

AbstractRational design of high-performance stable metal–organic framework (MOF) membranes is challenging, especially for the sustainable treatment of hypersaline waters to address critical global environmental issues. Herein, a molecular-level intra-crystalline defect strategy combined with a selective layer thinning protocol is proposed to fabricate robust ultrathin missing-linker UiO-66 (ML-UiO-66) membrane to enable fast water permeation. Besides almost complete salt rejection, high and stable water flux is achieved even under long-term pervaporation operation in hash environments, which effectively addresses challenging stability issues. Then, detailed structural characterizations are employed to identify the type, chemical functionality, and density of intra-crystalline missing-linker defects. Moreover, molecular dynamics simulations shed light on the positive atomistic role of these defects, which are responsible for substantially enhancing structural hydrophilicity and enlarging pore window, consequently allowing ultra-fast water transport via a lower-energy-barrier pathway across three-dimensional sub-nanochannels during pervaporation. Unlike common unfavorable defect effects, the present positive intra-crystalline defect engineering concept at the molecular level is expected to pave a promising way toward not only rational design of next-generation MOF membranes with enhanced permeation performance, but additional water treatment applications.
Phase controlled synthesis of transition metal carbide nanocrystals by ultrafast flash Joule heating
Authors: Deng Bing , Wang Zhe , Chen Weiyin , Li John Tianci , Luong Duy Xuan , Carter Robert A. , Gao Guanhui , Yakobson Boris I. , Zhao Yufeng , Tour James M. 
Published: January 2022

AbstractNanoscale carbides enhance ultra-strong ceramics and show activity as high-performance catalysts. Traditional lengthy carburization methods for carbide syntheses usually result in coked surface, large particle size, and uncontrolled phase. Here, a flash Joule heating process is developed for ultrafast synthesis of carbide nanocrystals within 1 s. Various interstitial transition metal carbides (TiC, ZrC, HfC, VC, NbC, TaC, Cr2C3, MoC, and W2C) and covalent carbides (B4C and SiC) are produced using low-cost precursors. By controlling pulse voltages, phase-pure molybdenum carbides including β-Mo2C and metastable α-MoC1-x and η-MoC1-x are selectively synthesized, demonstrating the excellent phase engineering ability of the flash Joule heating by broadly tunable energy input that can exceed 3000 K coupled with kinetically controlled ultrafast cooling (>104 K s−1). Theoretical calculation reveals carbon vacancies as the driving factor for topotactic transition of carbide phases. The phase-dependent hydrogen evolution capability of molybdenum carbides is investigated with β-Mo2C showing the best performance.
Ultrafast coherent control of a hole spin qubit in a germanium quantum dot
Authors: Wang Ke , Xu Gang , Gao Fei , Liu He , Ma Rong-Long , Zhang Xin , Wang Zhanning , Cao Gang , Wang Ting , Zhang Jian-Jun , Culcer Dimitrie , Hu Xuedong , Jiang Hong-Wen , Li Hai-Ou , Guo Guang-Can , Guo Guo-Ping 
Published: January 2022

AbstractOperation speed and coherence time are two core measures for the viability of a qubit. Strong spin-orbit interaction (SOI) and relatively weak hyperfine interaction make holes in germanium (Ge) intriguing candidates for spin qubits with rapid, all-electrical coherent control. Here we report ultrafast single-spin manipulation in a hole-based double quantum dot in a germanium hut wire (GHW). Mediated by the strong SOI, a Rabi frequency exceeding 540 MHz is observed at a magnetic field of 100 mT, setting a record for ultrafast spin qubit control in semiconductor systems. We demonstrate that the strong SOI of heavy holes (HHs) in our GHW, characterized by a very short spin-orbit length of 1.5 nm, enables the rapid gate operations we accomplish. Our results demonstrate the potential of ultrafast coherent control of hole spin qubits to meet the requirement of DiVincenzo’s criteria for a scalable quantum information processor.
Comparing ultrastable lasers at 7 × 10−17 fractional frequency instability through a 2220 km optical fibre network
Authors: Schioppo M. , Kronjäger J. , Silva A. , Ilieva R. , Paterson J. W. , Baynham C. F. A. , Bowden W. , Hill I. R. , Hobson R. , Vianello A. , Dovale-Álvarez M. , Williams R. A. , Marra G. , Margolis H. S. , Amy-Klein A. , Lopez O. , Cantin E. , Álvarez-Martínez H. , Le Targat R. , Pottie P. E. , Quintin N. , Legero T. , Häfner S. , Sterr U. , Schwarz R. , Dörscher S. , Lisdat C. , Koke S. , Kuhl A. , Waterholter T. , Benkler E. , Grosche G. 
Published: January 2022

AbstractUltrastable lasers are essential tools in optical frequency metrology enabling unprecedented measurement precision that impacts on fields such as atomic timekeeping, tests of fundamental physics, and geodesy. To characterise an ultrastable laser it needs to be compared with a laser of similar performance, but a suitable system may not be available locally. Here, we report a comparison of two geographically separated lasers, over the longest ever reported metrological optical fibre link network, measuring 2220 km in length, at a state-of-the-art fractional-frequency instability of 7 × 10−17 for averaging times between 30 s and 200 s. The measurements also allow the short-term instability of the complete optical fibre link network to be directly observed without using a loop-back fibre. Based on the characterisation of the noise in the lasers and optical fibre link network over different timescales, we investigate the potential for disseminating ultrastable light to improve the performance of remote optical clocks.
Distinct mechanisms orchestrate the contra-polarity of IRK and KOIN, two LRR-receptor-kinases controlling root cell division
Authors: Rodriguez-Furlan Cecilia , Campos Roya , Toth Jessica N. , Van Norman Jaimie M. 
Published: January 2022

AbstractIn plants, cell polarity plays key roles in coordinating developmental processes. Despite the characterization of several polarly localized plasma membrane proteins, the mechanisms connecting protein dynamics with cellular functions often remain unclear. Here, we introduce a polarized receptor, KOIN, that restricts cell divisions in the Arabidopsis root meristem. In the endodermis, KOIN polarity is opposite to IRK, a receptor that represses endodermal cell divisions. Their contra-polar localization facilitates dissection of polarity mechanisms and the links between polarity and function. We find that IRK and KOIN are recognized, sorted, and secreted through distinct pathways. IRK extracellular domains determine its polarity and partially rescue the mutant phenotype, whereas KOIN’s extracellular domains are insufficient for polar sorting and function. Endodermal expression of an IRK/KOIN chimera generates non-cell-autonomous misregulation of root cell divisions that impacts patterning. Altogether, we reveal two contrasting mechanisms determining these receptors’ polarity and link their polarity to cell divisions in root tissue patterning.
MAPK4 promotes triple negative breast cancer growth and reduces tumor sensitivity to PI3K blockade
Authors: Wang Wei , Han Dong , Cai Qinbo , Shen Tao , Dong Bingning , Lewis Michael T. , Wang Runsheng , Meng Yanling , Zhou Wolong , Yi Ping , Creighton Chad J. , Moore David D. , Yang Feng 
Published: January 2022

AbstractAbout 15–20% of breast cancer (BCa) is triple-negative BCa (TNBC), a devastating disease with limited therapeutic options. Aberrations in the PI3K/PTEN signaling pathway are common in TNBC. However, the therapeutic impact of PI3K inhibitors in TNBC has been limited and the mechanism(s) underlying this lack of efficacy remain elusive. Here, we demonstrate that a large subset of TNBC expresses significant levels of MAPK4, and this expression is critical for driving AKT activation independent of PI3K and promoting TNBC cell and xenograft growth. The ability of MAPK4 to bypass PI3K for AKT activation potentially provides a direct mechanism regulating tumor sensitivity to PI3K inhibition. Accordingly, repressing MAPK4 greatly sensitizes TNBC cells and xenografts to PI3K blockade. Altogether, we conclude that high MAPK4 expression defines a large subset or subtype of TNBC responsive to MAPK4 blockage. Targeting MAPK4 in this subset/subtype of TNBC both represses growth and sensitizes tumors to PI3K blockade.
Gut microbiome development in early childhood is affected by day care attendance
Authors: Amir Amnon , Erez-Granat Ortal , Braun Tzipi , Sosnovski Katya , Hadar Rotem , BenShoshan Marina , Heiman Sophia , Abbas-Egbariya Haya , Glick Saar Efrat , Efroni Gilat , Haberman Yael 
Published: January 2022

AbstractThe human gut microbiome develops during the first years of life, followed by a relatively stable adult microbiome. Day care attendance is a drastic change that exposes children to a large group of peers in a diverse environment for prolonged periods, at this critical time of microbial development, and therefore has the potential to affect microbial composition. We characterize the effect of day care on the gut microbial development throughout a single school year in 61 children from 4 different day care facilities, and in additional 24 age-matched home care children (n = 268 samples, median age of entering the study was 12 months). We show that day care attendance is a significant and impactful factor in shaping the microbial composition of the growing child, the specific daycare facility and class influence the gut microbiome, and each child becomes more similar to others in their day care. Furthermore, in comparison to home care children, day care children have a different gut microbial composition, with enrichment of taxa more frequently observed in older populations. Our results provide evidence that daycare may be an external factor that contributes to gut microbiome maturation and make-up in early childhood.