bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell trajectory analysis of human homogenous neurons carrying a rare RELN variant
Authors: Arioka Yuko , Shishido Emiko , Kubo Hisako , Kushima Itaru , Yoshimi Akira , Kimura Hiroki , Ishizuka Kanako , Aleksic Branko , Maeda Takuji , Ishikawa Mitsuru , Kuzumaki Naoko , Okano Hideyuki , Mori Daisuke , Ozaki Norio 
Published: July 2018

AbstractReelin is a protein encoded by the RELN gene that controls neuronal migration in the developing brain. Human genetic studies suggest that rare RELN variants confer susceptibility to mental disorders such as schizophrenia. However, it remains unknown what effects rare RELN variants have on human neuronal cells. To this end, the analysis of human neuronal dynamics at the single-cell level is necessary. In this study, we generated human-induced pluripotent stem cells carrying a rare RELN variant (RELN-del) using targeted genome editing; cells were further differentiated into highly homogeneous dopaminergic neurons. Our results indicated that RELN-del triggered an impaired reelin signal and decreased the expression levels of genes relevant for cell movement in human neurons. Single-cell trajectory analysis revealed that control neurons possessed directional migration even in vitro, while RELN-del neurons demonstrated a wandering type of migration. We further confirmed these phenotypes in neurons derived from a patient carrying the congenital RELN-del. To our knowledge, this is the first report of the biological significance of a rare RELN variant in human neurons based on individual neuron dynamics. Collectively, our approach should be useful for studying reelin function and evaluating mental disorder susceptibility, focusing on individual human neuronal migration.
M2 macrophage-mediated interleukin-4 signalling induces myofibroblast phenotype during the progression of benign prostatic hyperplasia
Authors: Sheng Jindong , Yang Yang , Cui Yun , He Shiming , Wang Lu , Liu Libo , He Qun , Lv Tianjing , Han Wenke , Yu Wei , Hu Shuai , Jin Jie 
Published: July 2018

AbstractBenign prostatic hyperplasia (BPH) is a progressive disease in elderly men, but potential factors accelerating its progression remain largely unknown. The aim of this study was to elucidate the factors affecting BPH progression by understanding the complex mechanisms causing early- progressed BPH, which progresses rapidly and requires surgical intervention before the age of 50. Three groups of human prostate tissue samples, from patients with early-progressed BPH, age-matched prostate and elderly BPH tissues, were collected (n = 25 each). We compared these tissues to determine the histologic features and molecular mechanisms underlying BPH progression. We found that early-progressed BPH samples were characterised by aberrant stromal hyper-proliferation, collagen deposition and increased M2 macrophage infiltration, compared to those from age-matched prostate and elderly BPH tissues. The M2 macrophage–fibroblast co-culture system demonstrated that the myofibroblast phenotypes were strongly induced only in fibroblasts from the early-progressed BPH samples, while the co-cultured M2 macrophages expressed high levels of pro-fibrotic cytokines, such as IL4 and TGFβ1. M2 macrophage-derived IL4, but not TGFβ1, selectively induced the myofibroblast phenotype through the JAK/STAT6, PI3K/AKT and MAPK/ERK signalling pathways in the early-progressed BPH prostate fibroblasts. Taken together, our results indicate that induction of the myofibroblast phenotype may lead to BPH progression through M2 macrophage-mediated IL4 signalling, and that IL4 may represent a potential therapeutic target, allowing the prevention of M2 macrophage activation and fibroblast-to-myofibroblast differentiation.
ER stress regulating protein phosphatase 2A-B56γ, targeted by hepatitis B virus X protein, induces cell cycle arrest and apoptosis of hepatocytes
Authors: He Chengyong , Qiu Yang , Han Peiyu , Chen Yuanyuan , Zhang Liyin , Yuan Quan , Zhang Tianying , Cheng Tong , Yuan Lunzhi , Huang Chenghao , Zhang Sheng , Yin Zhenyu , Peng Xian-E. , Liang Dong , Lin Xu , Lin Yuchun , Lin Zhongning , Xia Ningshao 
Published: July 2018

AbstractHepatitis B virus X (HBx) protein contributes to the progression of hepatitis B virus (HBV)-related hepatic injury and diseases, but the exact mechanism remains unclear. Protein phosphatase 2 A (PP2A) is a major serine/threonine phosphatase involved in regulating many cellular phosphorylation signals that are important for regulation of cell cycle and apoptosis. Does HBx target to PP2A-B56γ and therefore affect HBx-induced hepatotoxicity? In the present study, the expression of B56γ positively correlated with the level of HBx in HBV-infected primary human hepatocytes in human-liver-chimeric mice, HBx-transgenic mice, HBV-infected cells, and HBx-expressing hepatic cells. B56γ promoted p53/p21-dependent cell cycle arrest and apoptosis. Mechanistically, B56γ was transactivated by AP-1, which was under the regulation of endoplasmic reticulum (ER) stress induced CREBH signaling in HBx-expressing hepatic cells. B56γ dephosphorylated p-Thr55-p53 to trigger p53/p21 pathway-dependent cell cycle G1 phase arrest, resulting in apoptosis of hepatic cells. In conclusion, this study provides a novel insight into a mechanism of B56γ mediating cell cycle arrest and apoptosis of HBx-expressing hepatic cells and a basis for B56γ being a potential therapeutic target for HBV-infected hepatic cells.
Human umbilical cord-derived mesenchymal stem cells direct macrophage polarization to alleviate pancreatic islets dysfunction in type 2 diabetic mice
Authors: Yin Yaqi , Hao Haojie , Cheng Yu , Zang Li , Liu Jiejie , Gao Jieqing , Xue Jing , Xie Zongyan , Zhang Qi , Han Weidong , Mu Yiming 
Published: July 2018

AbstractProgressive pancreatic β-cell dysfunction is recognized as a fundamental pathology of type 2 diabetes (T2D). Recently, mesenchymal stem cells (MSCs) have been identified in protection of islets function in T2D individuals. However, the underlying mechanisms remain elusive. It is widely accepted that β-cell dysfunction is closely related to improper accumulation of macrophages in the islets, and a series of reports suggest that MSCs possess great immunomodulatory properties by which they could elicit macrophages into an anti-inflammatory M2 state. In this study, we induced a T2D mouse model with a combination of high-fat diet (HFD) and low-dose streptozotocin (STZ), and then performed human umbilical cord-derived MSCs (hUC-MSCs) infusion to investigate whether the effect of MSCs on islets protection was related to regulation on macrophages in pancreatic islets. hUC-MSCs infusion exerted anti-diabetic effects and significantly promoted islets recovery in T2D mice. Interestingly, pancreatic inflammation was remarkably suppressed, and local M1 macrophages were directed toward an anti-inflammatory M2-like state after hUC-MSC infusion. In vitro study also proved that hUC-MSCs inhibited the activation of the M1 phenotype and induced the generation of the M2 phenotype in isolated mouse bone marrow-derived macrophages (BMDMs), peritoneal macrophages (PMs) and in THP-1 cells. Further analysis showed that M1-stimulated hUC-MSCs increased the secretion of interleukin (IL)-6, blocking which by small interfering RNA (siRNA) largely abrogated the hUC-MSCs effects on macrophages both in vitro and in vivo, resulting in dampened restoration of β-cell function and glucose homeostasis in T2D mice. In addition, MCP-1 was found to work in accordance with IL-6 in directing macrophage polarization from M1 to M2 state. These data may provide new clues for searching for the target of β-cell protection. Furthermore, hUC-MSCs may be a superior alternative in treating T2D for their macrophage polarization effects.
CD45+CD33lowCD11bdim myeloid-derived suppressor cells suppress CD8+ T cell activity via the IL-6/IL-8-arginase I axis in human gastric cancer
Authors: Mao Fang-yuan , Zhao Yong-liang , Lv Yi-pin , Teng Yong-sheng , Kong Hui , Liu Yu-gang , Wu Xiao-long , Hao Chuan-jie , Chen Weisan , Duan Mu-bing , Han Bin , Ma Qiang , Wang Ting-ting , Peng Liu-sheng , Zhang Jin-yu , Cheng Ping , Su Chong-yu , Fu Xiao-long , Zou Quan-ming , Guo Gang , Guo Xiao-lan , Zhuang Yuan 
Published: July 2018

AbstractMyeloid-derived suppressor cells (MDSCs) are a prominent component of the pro-tumoral response. The phenotype of and mechanisms used by MDSCs is heterogeneous and requires more precise characterization in gastric cancer (GC) patients. Here, we have identified a novel subset of CD45+CD33lowCD11bdim MDSCs in the peripheral blood of GC patients compared to healthy individuals. CD45+CD33lowCD11bdim MDSCs morphologically resembled neutrophils and expressed high levels of the neutrophil marker CD66b. Circulating CD45+CD33lowCD11bdim MDSCs effectively suppressed CD8+ T cells activity through the inhibition of CD8+ T cell proliferation and interferon-γ (IFN-γ) and granzyme B (GrB) production. The proportion of CD45+CD33lowCD11bdim MDSCs also negatively correlated with the proportion of IFN-γ+CD8+ T cell in the peripheral blood of GC patients. GC patient serum-derived IL-6 and IL-8 activated and induced CD45+CD33lowCD11bdim MDSCs to express arginase I via the PI3K-AKT signaling pathway. This pathway contributed to CD8+ T cell suppression as it was partially rescued by the blockade of the IL-6/IL-8-arginase I axis. Peripheral blood CD45+CD33lowCD11bdim MDSCs, as well as IL-6, IL-8, and arginase I serum levels, positively correlated with GC progression and negatively correlated with overall patient survival. Altogether, our results highlight that a subset of neutrophilic CD45+CD33lowCD11bdim MDSCs is functionally immunosuppressive and activated via the IL-6/IL-8-arginase I axis in GC patients.
Dynamic placement of the linker histone H1 associated with nucleosome arrangement and gene transcription in early Drosophila embryonic development
Authors: Hu Jian , Gu Liang , Ye Youqiong , Zheng Meizhu , Xu Zhu , Lin Jing , Du Yanhua , Tian Mengxue , Luo Lifang , Wang Beibei , Zhang Xiaobai , Weng Zhiping , Jiang Cizhong 
Published: July 2018

AbstractThe linker histone H1 is critical to maintenance of higher-order chromatin structures and to gene expression regulation. However, H1 dynamics and its functions in embryonic development remain unresolved. Here, we profiled gene expression, nucleosome positions, and H1 locations in early Drosophila embryos. The results show that H1 binding is positively correlated with the stability of beads-on-a-string nucleosome organization likely through stabilizing nucleosome positioning and maintaining nucleosome spacing. Strikingly, nucleosomes with H1 placement deviating to the left or the right relative to the dyad shift to the left or the right, respectively, during early Drosophila embryonic development. H1 occupancy on genic nucleosomes is inversely correlated with nucleosome distance to the transcription start sites. This inverse correlation reduces as gene transcription levels decrease. Additionally, H1 occupancy is lower at the 5′ border of genic nucleosomes than that at the 3′ border. This asymmetrical pattern of H1 occupancy on genic nucleosomes diminishes as gene transcription levels decrease. These findings shed new lights into how H1 placement dynamics correlates with nucleosome positioning and gene transcription during early Drosophila embryonic development.
Pontin/Tip49 negatively regulates JNK-mediated cell death in Drosophila
Authors: Wang Xingjun , Huang Xirui , Wu Chenxi , Xue Lei 
Published: July 2018

AbstractPontin (Pont), also known as Tip49, encodes a member of the AAA+ (ATPases Associated with Diverse Cellular Activities) superfamily and plays pivotal roles in cell proliferation and growth, yet its function in cell death has remained poorly understood. Here we performed a genetic screen for dominant modifiers of Eiger-induced JNK-dependent cell death in Drosophila, and identified Pont as a negative regulator of JNK-mediated cell death. In addition, loss of function of Pont is sufficient to induce cell death and activate the transcription of JNK target gene puc. Furthermore, the epistasis analysis indicates that Pont acts downstream of Hep. Finally, we found that Pont is also required for JNK-mediated thorax development and acts as a negative regulator of JNK phosphorylation. Together, our data suggest that pont encodes a negative component of Egr/JNK signaling pathway in Drosophila through negatively regulating JNK phosphorylation, which provides a novel role of ATPase in Egr-JNK signaling.
HHEX is a transcriptional regulator of the VEGFC/FLT4/PROX1 signaling axis during vascular development
Authors: Gauvrit Sébastien , Villasenor Alethia , Strilic Boris , Kitchen Philip , Collins Michelle M. , Marín-Juez Rubén , Guenther Stefan , Maischein Hans-Martin , Fukuda Nana , Canham Maurice A. , Brickman Joshua M. , Bogue Clifford W. , Jayaraman Padma-Sheela , Stainier Didier Y. R. 
Published: July 2018

AbstractFormation of the lymphatic system requires the coordinated expression of several key regulators: vascular endothelial growth factor C (VEGFC), its receptor FLT4, and a key transcriptional effector, PROX1. Yet, how expression of these signaling components is regulated remains poorly understood. Here, using a combination of genetic and molecular approaches, we identify the transcription factor hematopoietically expressed homeobox (HHEX) as an upstream regulator of VEGFC, FLT4, and PROX1 during angiogenic sprouting and lymphatic formation in vertebrates. By analyzing zebrafish mutants, we found that hhex is necessary for sprouting angiogenesis from the posterior cardinal vein, a process required for lymphangiogenesis. Furthermore, studies of mammalian HHEX using tissue-specific genetic deletions in mouse and knockdowns in cultured human endothelial cells reveal its highly conserved function during vascular and lymphatic development. Our findings that HHEX is essential for the regulation of the VEGFC/FLT4/PROX1 axis provide insights into the molecular regulation of lymphangiogenesis.
Influence of atomic site-specific strain on catalytic activity of supported nanoparticles
Authors: Nilsson Pingel Torben , Jørgensen Mikkel , Yankovich Andrew B. , Grönbeck Henrik , Olsson Eva 
Published: July 2018

AbstractHeterogeneous catalysis is an enabling technology that utilises transition metal nanoparticles (NPs) supported on oxides to promote chemical reactions. Structural mismatch at the NP–support interface generates lattice strain that could affect catalytic properties. However, detailed knowledge about strain in supported NPs remains elusive. We experimentally measure the strain at interfaces, surfaces and defects in Pt NPs supported on alumina and ceria with atomic resolution using high-precision scanning transmission electron microscopy. The largest strains are observed at the interfaces and are predominantly compressive. Atomic models of Pt NPs with experimentally measured strain distributions are used for first-principles kinetic Monte Carlo simulations of the CO oxidation reaction. The presence of only a fraction of strained surface atoms is found to affect the turnover frequency. These results provide a quantitative understanding of the relationship between strain and catalytic function and demonstrate that strain engineering can potentially be used for catalyst design.
Population genomics of hypervirulent Klebsiella pneumoniae clonal-group 23 reveals early emergence and rapid global dissemination
Authors: Lam Margaret M. C. , Wyres Kelly L. , Duchêne Sebastian , Wick Ryan R. , Judd Louise M. , Gan Yunn-Hwen , Hoh Chu-Han , Archuleta Sophia , Molton James S. , Kalimuddin Shirin , Koh Tse Hsien , Passet Virginie , Brisse Sylvain , Holt Kathryn E. 
Published: July 2018

AbstractSevere liver abscess infections caused by hypervirulent clonal-group CG23 Klebsiella pneumoniae have been increasingly reported since the mid-1980s. Strains typically possess several virulence factors including an integrative, conjugative element ICEKp encoding the siderophore yersiniabactin and genotoxin colibactin. Here we investigate CG23’s evolutionary history, showing several deep-branching sublineages associated with distinct ICEKp acquisitions. Over 80% of liver abscess isolates belong to sublineage CG23-I, which emerged in ~1928 following acquisition of ICEKp10 (encoding yersiniabactin and colibactin), and then disseminated globally within the human population. CG23-I’s distinguishing feature is the colibactin synthesis locus, which reportedly promotes gut colonisation and metastatic infection in murine models. These data show circulation of CG23 K. pneumoniae decades before the liver abscess epidemic was first recognised, and provide a framework for future epidemiological and experimental studies of hypervirulent K. pneumoniae. To support such studies we present an open access, completely sequenced CG23-I human liver abscess isolate, SGH10.
Limits to growth of forest biomass carbon sink under climate change
Authors: Zhu Kai , Zhang Jian , Niu Shuli , Chu Chengjin , Luo Yiqi 
Published: July 2018

AbstractWidely recognized as a significant carbon sink, North American forests have experienced a history of recovery and are facing an uncertain future. This growing carbon sink is dictated by recovery from land-use change, with growth trajectory modified by environmental change. To address both processes, we compiled a forest inventory dataset from North America to quantify aboveground biomass growth with stand age across forest types and climate gradients. Here we show, the biomass grows from 90 Mg ha–1 (2000–2016) to 105 Mg ha–1 (2020 s), 128 Mg ha–1 (2050 s), and 146 Mg ha–1 (2080 s) under climate change scenarios with no further disturbances. Climate change modifies the forest recovery trajectory to some extent, but the overall growth is limited, showing signs of biomass saturation. The future (2080s) biomass will only sequester at most 22% more carbon than the current level. Given such a strong sink has limited growth potential, our ground-based analysis suggests policy changes to sustain the carbon sink.
KIF20A/MKLP2 regulates the division modes of neural progenitor cells during cortical development
Authors: Geng Anqi , Qiu Runxiang , Murai Kiyohito , Liu Jiancheng , Wu Xiwei , Zhang Heying , Farhoodi Henry , Duong Nam , Jiang Meisheng , Yee Jiing-kuan , Tsark Walter , Lu Qiang 
Published: July 2018

AbstractBalanced symmetric and asymmetric divisions of neural progenitor cells (NPCs) are crucial for brain development, but the underlying mechanisms are not fully understood. Here we report that mitotic kinesin KIF20A/MKLP2 interacts with RGS3 and plays a crucial role in controlling the division modes of NPCs during cortical neurogenesis. Knockdown of KIF20A in NPCs causes dislocation of RGS3 from the intercellular bridge (ICB), impairs the function of Ephrin-B–RGS cell fate signaling complex, and leads to a transition from proliferative to differentiative divisions. Germline and inducible knockout of KIF20A causes a loss of progenitor cells and neurons and results in thinner cortex and ventriculomegaly. Interestingly, loss of function of KIF20A induces early cell cycle exit and precocious neuronal differentiation without causing substantial cytokinesis defect or apoptosis. Our results identify a RGS–KIF20A axis in the regulation of cell division and suggest a potential link of the ICB to regulation of cell fate determination.
Magnetostatic twists in room-temperature skyrmions explored by nitrogen-vacancy center spin texture reconstruction
Authors: Dovzhenko Y. , Casola F. , Schlotter S. , Zhou T. X. , Büttner F. , Walsworth R. L. , Beach G. S. D. , Yacoby A. 
Published: July 2018

AbstractMagnetic skyrmions are two-dimensional non-collinear spin textures characterized by an integer topological number. Room-temperature skyrmions were recently found in magnetic multilayer stacks, where their stability was largely attributed to the interfacial Dzyaloshinskii–Moriya interaction. The strength of this interaction and its role in stabilizing the skyrmions is not yet well understood, and imaging of the full spin structure is needed to address this question. Here, we use a nitrogen-vacancy centre in diamond to measure a map of magnetic fields produced by a skyrmion in a magnetic multilayer under ambient conditions. We compute the manifold of candidate spin structures and select the physically meaningful solution. We find a Néel-type skyrmion whose chirality is not left-handed, contrary to preceding reports. We propose skyrmion tube-like structures whose chirality rotates through the film thickness. We show that NV magnetometry, combined with our analysis method, provides a unique tool to investigate this previously inaccessible phenomenon.
Skilful forecasting of global fire activity using seasonal climate predictions
Authors: Turco Marco , Jerez Sonia , Doblas-Reyes Francisco J. , AghaKouchak Amir , Llasat Maria Carmen , Provenzale Antonello 
Published: July 2018

AbstractSocietal exposure to large fires has been increasing in recent years. Estimating the expected fire activity a few months in advance would allow reducing environmental and socio-economic impacts through short-term adaptation and response to climate variability and change. However, seasonal prediction of climate-driven fires is still in its infancy. Here, we discuss a strategy for seasonally forecasting burned area anomalies linking seasonal climate predictions with parsimonious empirical climate–fire models using the standardized precipitation index as the climate predictor for burned area. Assuming near-perfect climate predictions, we obtained skilful predictions of fire activity over a substantial portion of the global burnable area (~60%). Using currently available operational seasonal climate predictions, the skill of fire seasonal forecasts remains high and significant in a large fraction of the burnable area (~40%). These findings reveal an untapped and useful burned area predictive ability using seasonal climate forecasts, which can play a crucial role in fire management strategies and minimise the impact of adverse climate conditions.
A rigid and healable polymer cross-linked by weak but abundant Zn(II)-carboxylate interactions
Authors: Lai Jian-Cheng , Li Lan , Wang Da-Peng , Zhang Min-Hao , Mo Sheng-Ran , Wang Xue , Zeng Ke-Yu , Li Cheng-Hui , Jiang Qing , You Xiao-Zeng , Zuo Jing-Lin 
Published: July 2018

AbstractAchieving a desirable combination of solid-like properties and fast self-healing is a great challenge due to slow diffusion dynamics. In this work, we describe a design concept that utilizes weak but abundant coordination bonds to achieve this objective. The designed PDMS polymer, crosslinked by abundant Zn(II)-carboxylate interactions, is very strong and rigid at room temperature. As the coordination equilibrium is sensitive to temperature, the mechanical strength of this polymer rapidly and reversibly changes upon heating or cooling. The soft–rigid switching ability σ, defined as G’max /G’min, can reach 8000 when ΔT = 100 °C. Based on these features, this polymer not only exhibits fast thermal-healing properties, but is also advantageous for various applications such as in orthopedic immobilization, conductive composites/adhesives, and 3D printing.