bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simultaneous Development of Multiple Auroral Substorms: Double Auroral Bulge Formation
Authors: Ohtani S. , Gjerloev J. W. , McWilliams K. A. , Ruohoniemi J. M. , Frey H. U. 
Published: May 2021

AbstractThe expansion phase of auroral substorms is characterized by the formation of an auroral bulge, and it is generally considered that a single bulge forms following each substorm onset. However, we find that occasionally two auroral intensifications takes place close in time but apart in space leading to the formation of double auroral bulges, which later merge into one large bulge. We report three such events. In those events the westward auroral electrojet intensified in each auroral bulge, and geosynchronous magnetic field dipolarized in the same sector. It appears that two substorms took place simultaneously, and each substorm was accompanied by the formation of its own substorm current wedge system. This finding strongly suggests that the initiation of auroral substorms is a local process, and there is no global reference frame for their development. For example, ideas such as (i) the auroralbreakup takes place in the vicinity of the Harang reversal and (ii) the westward traveling surge maps to the interface between the plasma sheet and low‐latitude boundary layer, do not necessarily hold for every substorm. Even if those ideas may be suggestive of causal magnetospheric processes, the reference structures themselves are probably not essential. It is also found that despite the formation of two distinct auroral bulges, the overall magnetosphere‐ionosphere current system is represented by one globally coherent system, and we suggest that its structure is determined by the relative intensities and locations of the two substorm current wedges that correspond to the individual auroral bulges.
The Inertia‐Based Model for Reconstruction of the Electron Diffusion Region
Authors: Korovinskiy D. B. , Kiehas S. A. , Panov E. V. , Semenov V. S. , Erkaev N. V. , Divin A. V. , Kubyshkin I. V. 
Published: May 2021

AbstractThe present study is focused on the problem of reconstruction of the magnetic configuration in the magnetic reconnection electron diffusion region (EDR). The problem is addressed in the frame of electron magnetohydrodynamics with kept electron inertia term. We introduce the new reconstruction model independent of divergence of the electron pressure tensor and reconnection electric field. The model is tested on the magnetotail reconnection event of July 11, 2017 observed by the Magnetospheric Multiscale (MMS) spacecraft in the course of crossing the very core part of the reconnection region, the internal EDR. This new model demonstrates considerably better accuracy of the longitudinal electron velocity reconstruction due to the lower sensitivity to the configuration deviation from the two‐dimensional time‐independent model adopted in our study. We suggest also a new technique to estimate the guide field, implementing the reconstruction of magnetic potential of the in‐plane magnetic field and relying on symmetric properties of magnetic reconnection.
Nanophotonics enhanced coverslip for phase imaging in biology
Authors: Wesemann Lukas , Rickett Jon , Song Jingchao , Lou Jieqiong , Hinde Elizabeth , Davis Timothy J. , Roberts Ann 
Published: May 2021

AbstractThe ability to visualise transparent objects such as live cells is central to understanding biological processes. Here we experimentally demonstrate a novel nanostructured coverslip that converts phase information to high-contrast intensity images. This compact device enables real-time, all-optical generation of pseudo three-dimensional images of phase objects on transmission. We show that by placing unstained human cancer cells on the device, the internal structure within the cells can be clearly seen. Our research demonstrates the significant potential of nanophotonic devices for integration into compact imaging and medical diagnostic devices.
Deep-sea mussels from a hybrid zone on the Mid-Atlantic Ridge host genetically indistinguishable symbionts
Authors: Ücker Merle , Ansorge Rebecca , Sato Yui , Sayavedra Lizbeth , Breusing Corinna , Dubilier Nicole 
Published: May 2021

Abstract
The composition and diversity of animal microbiomes is shaped by a variety of factors, many of them interacting, such as host traits, the environment, and biogeography. Hybrid zones, in which the ranges of two host species meet and hybrids are found, provide natural experiments for determining the drivers of microbiome communities, but have not been well studied in marine environments. Here, we analysed the composition of the symbiont community in two deep-sea, Bathymodiolus mussel species along their known distribution range at hydrothermal vents on the Mid-Atlantic Ridge, with a focus on the hybrid zone where they interbreed. In-depth metagenomic analyses of the sulphur-oxidising symbionts of 30 mussels from the hybrid zone, at a resolution of single nucleotide polymorphism analyses of ~2500 orthologous genes, revealed that parental and hybrid mussels (F2–F4 generation) have genetically indistinguishable symbionts. While host genetics does not appear to affect symbiont composition in these mussels, redundancy analyses showed that geographic location of the mussels on the Mid-Atlantic Ridge explained most of the symbiont genetic variability compared to the other factors. We hypothesise that geographic structuring of the free-living symbiont population plays a major role in driving the composition of the microbiome in these deep-sea mussels.
Glyoxalase I disruption and external carbonyl stress impair mitochondrial function in human induced pluripotent stem cells and derived neurons
Authors: Hara Tomonori , Toyoshima Manabu , Hisano Yasuko , Balan Shabeesh , Iwayama Yoshimi , Aono Harumi , Futamura Yushi , Osada Hiroyuki , Owada Yuji , Yoshikawa Takeo 
Published: May 2021

AbstractCarbonyl stress, a specific form of oxidative stress, is reported to be involved in the pathophysiology of schizophrenia; however, little is known regarding the underlying mechanism. Here, we found that disruption of GLO1, the gene encoding a major catabolic enzyme scavenging the carbonyl group, increases vulnerability to external carbonyl stress, leading to abnormal phenotypes in human induced pluripotent stem cells (hiPSCs). The viability of GLO1 knockout (KO)-hiPSCs decreased and activity of caspase-3 was increased upon addition of methylglyoxal (MGO), a reactive carbonyl compound. In the GLO1 KO-hiPSC-derived neurons, MGO administration impaired neurite extension and cell migration. Further, accumulation of methylglyoxal-derived hydroimidazolone (MG-H1; a derivative of MGO)-modified proteins was detected in isolated mitochondria. Mitochondrial dysfunction, including diminished membrane potential and dampened respiratory function, was observed in the GLO1 KO-hiPSCs and derived neurons after addition of MGO and hence might be the mechanism underlying the effects of carbonyl stress. The susceptibility to MGO was partially rescued by the administration of pyridoxamine, a carbonyl scavenger. Our observations can be used for designing an intervention strategy for diseases, particularly those induced by enhanced carbonyl stress or oxidative stress.
WNT/β-catenin-suppressed FTO expression increases m6A of c-Myc mRNA to promote tumor cell glycolysis and tumorigenesis
Authors: Yang Xueying , Shao Fei , Guo Dong , Wang Wei , Wang Juhong , Zhu Rongxuan , Gao Yibo , He Jie , Lu Zhimin 
Published: May 2021

AbstractFTO removes the N6-methyladenosine (m6A) modification from genes and plays a critical role in cancer development. However, the mechanisms underlying the regulation of FTO and its subsequent impact on the regulation of the epitranscriptome remain to be further elucidated. Here, we demonstrate that FTO expression is downregulated and inversely correlated with poor survival of lung adenocarcinoma patients. Mechanistically, Wnt signaling induces the binding of EZH2 to β-catenin. This protein complex binds to the LEF/TCF-binding elements at the promoter region of FTO, where EZH2 enhances H3K27me3 and inhibits FTO expression. Downregulated FTO expression substantially enhances the m6A levels in the mRNAs of a large number of genes in critical pathways, particularly metabolic pathway genes, such as MYC. Enhanced m6A levels on MYC mRNA recruit YTHDF1 binding, which promotes MYC mRNA translation and a subsequent increase in glycolysis and proliferation of tumor cells and tumorigenesis. Our findings uncovered a critical mechanism of epitranscriptome regulation by Wnt/β-catenin-mediated FTO downregulation and underscored the role of m6A modifications of MYC mRNA in regulating tumor cell glycolysis and growth.
Inhibition of the sonic hedgehog pathway activates TGF-β-activated kinase (TAK1) to induce autophagy and suppress apoptosis in thyroid tumor cells
Authors: Li Sumei , Wang Jingxiang , Lu Yurong , Zhao Yuqing , Prinz Richard A. , Xu Xiulong 
Published: May 2021

AbstractThe sonic hedgehog (Shh) pathway is highly activated in a variety of malignancies and plays important roles in tumorigenesis, tumor growth, drug resistance, and metastasis. Our recent study showed that the inhibitors of the Shh pathway such as cyclopamine (CP), a Smothened (SMO) inhibitor, and GANT61, a Gli1 inhibitor, have modest inhibitory effects on thyroid tumor cell proliferation and tumor growth. The objective of this study was to determine whether autophagy was induced by inhibition of the Shh pathway and could negatively regulate GANT61-induced apoptosis. Here we report that inhibition of the Shh pathway by Gli1 siRNA or by cyclopamine and GANT61 induced autophagy in SW1736 and KAT-18 cells, two anaplastic thyroid cancer cell lines; whereas Gli1 overexpression suppressed autophagy. Mechanistic investigation revealed that inhibition of the Shh pathway activated TAK1 and its two downstream kinases, the c-Jun-terminal kinase (JNK) and AMP-activated protein kinase (AMPK). GANT61-induced autophagy was blocked by TAK1 siRNA and the inhibitors of TAK1 (5Z-7-oxozeaenol, 5Z), JNK (SP600125), and AMPK (Compound C, CC). Inhibition of autophagy by chloroquine and 5Z and by TAK1 and Beclin-1 siRNA enhanced GANT61-induced apoptosis and its antiproliferative activity. Our study has shown that inhibition of the Shh pathway induces autophagy by activating TAK1, whereas autophagy in turn suppresses GANT61-induced apoptosis. We have uncovered a previously unrecognized role of TAK1 in Shh pathway inhibition-induced autophagy and apoptosis.
DNAJB9 suppresses the metastasis of triple-negative breast cancer by promoting FBXO45-mediated degradation of ZEB1
Authors: Kim Hye-Youn , Kim Young-Mi , Hong Suntaek 
Published: May 2021

AbstractDNAJB9, a member of the heat shock protein 40 family, acts as a multifunctional player involved in the maintenance of their client proteins and cellular homeostasis. However, the mechanistic action of DNAJB9 in human malignancies is yet to be fully understood. In this study, we found that ectopic restoration of DNAJB9 inhibits the migration, invasion, in vivo metastasis, and lung colonization of triple-negative breast cancer (TNBC) cells. Mechanistically, DNAJB9 stabilizes FBXO45 protein by suppressing self-ubiquitination and reduces the abundance of ZEB1 by Lys48-linked polyubiquitination to inhibit the epithelial–mesenchymal transition (EMT) and metastasis. Clinically, the reduction of DNAJB9 expression, concomitant with decreased FBXO45 abundance in breast cancer tissues, correlates with poorer clinical outcomes of patients with breast cancer. Taken together, our results provide a novel insight into the metastasis of TNBC and define a promising therapeutic strategy for cancers with overactive ZEB1 by regulating the DNAJB9–FBXO45 signaling axis.
Silencing TAK1 reduces MAPKs-MMP2/9 expression to reduce inflammation-driven neurohistological disruption post spinal cord injury
Authors: Jiang Shuai , Wu Yandan , Wu Shunjie , Ye Suhui , Kong Renyi , Chang Jie , Xia Mingjie , Bao Junping , Peng Xin , Hong Xin , Qian Zhanyang , Li Haijun 
Published: May 2021

AbstractMicroglia activation post traumatic spinal cord injury (SCI) provokes accumulation of inflammatory metabolites, leading to increasing neurological disruption. Our previous studies demonstrated that blocking MAPKs pathway mitigated microglia inflammatory activation and prevented cords from neuroinflammation-induced secondary injury. Transforming growth factor-β-activated kinase 1 (TAK1) is an upstream gate regulating activation of MAPKs signaling. To validate the therapeutic effect of TAK1 inhibition in neuroinflammation post SCI, in the current study, cultures of microglia BV2 line was undergone lipopolysaccharide (LPS) stimulation in the presence of TAK1 inhibitor 5Z-7-Oxozeaenol (ZO), LPS, or control. LPS triggered inflammatory level, cell migration, and matrix metalloproteinase (MMP) 2/9 production, which was reduced in ZO-treated cultures. TAK1 inhibition by ZO also decreased activation of MAPKs pathway, indicating that ZO-mediated alleviation of neuroinflammation is likely modulated via TAK1/MAPKs axis. In vivo, neuroinflammatory level and tissue destruction were assessed in adult male mice that were undergone SCI by mechanical trauma, and treated with ZO by intraperitoneal injection. Compared with SCI mice, ZO-treated mice exhibited less microglia pro-inflammatory activation and accumulation adjacent to injured core linked to reduced MMP2/9 expression, leading to minor tissue damage and better locomotor recovery. To sum up, the obtained data proved that in the early phase post SCI, TAK1 inhibition impedes microglia biological activities including activation, enzymatic synthesis, and migration via downregulation of MAPKs pathway, and the effects may be accurately characterized as potent anti-inflammation.
Lung cancer organoids analyzed on microwell arrays predict drug responses of patients within a week
Authors: Hu Yawei , Sui Xizhao , Song Fan , Li Yaqian , Li Kaiyi , Chen Zhongyao , Yang Fan , Chen Xiuyuan , Zhang Yaohua , Wang Xianning , Liu Qiang , Li Cong , Zou Binbin , Chen Xiaofang , Wang Jun , Liu Peng 
Published: May 2021

AbstractWhile the potential of patient-derived organoids (PDOs) to predict patients’ responses to anti-cancer treatments has been well recognized, the lengthy time and the low efficiency in establishing PDOs hamper the implementation of PDO-based drug sensitivity tests in clinics. We first adapt a mechanical sample processing method to generate lung cancer organoids (LCOs) from surgically resected and biopsy tumor tissues. The LCOs recapitulate the histological and genetic features of the parental tumors and have the potential to expand indefinitely. By employing an integrated superhydrophobic microwell array chip (InSMAR-chip), we demonstrate hundreds of LCOs, a number that can be generated from most of the samples at passage 0, are sufficient to produce clinically meaningful drug responses within a week. The results prove our one-week drug tests are in good agreement with patient-derived xenografts, genetic mutations of tumors, and clinical outcomes. The LCO model coupled with the microwell device provides a technically feasible means for predicting patient-specific drug responses in clinical settings.
Odd Willis coupling induced by broken time-reversal symmetry
Authors: Quan Li , Yves Simon , Peng Yugui , Esfahlani Hussein , Alù Andrea 
Published: May 2021

AbstractWhen sound interacts with geometrically asymmetric structures, it experiences coupling between pressure and particle velocity, known as Willis coupling. While in most instances this phenomenon is perturbative in nature, tailored asymmetries combined with resonances can largely enhance it, enabling exotic acoustic phenomena. In these systems, Willis coupling obeys reciprocity, imposing an even symmetry of the Willis coefficients with respect to time reversal and the impinging wave vector, which translates into stringent constraints on the overall scattering response. In this work, we introduce and experimentally observe a dual form of acoustic Willis coupling, arising in geometrically symmetric structures when time-reversal symmetry is broken, for which the pressure-velocity coupling is purely odd-symmetric. We derive the conditions to maximize this effect, we experimentally verify it in a symmetric subwavelength scatterer biased by angular momentum, and we demonstrate the opportunities for sound scattering enabled by odd Willis coupling. Our study opens directions for acoustic metamaterials, with direct implications for sound control, non-reciprocal scattering, wavefront shaping and signal routing, of broad interest also for nano-optics, photonics, elasto-dynamics, and mechanics.
Deep learning-based predictive identification of neural stem cell differentiation
Authors: Zhu Yanjing , Huang Ruiqi , Wu Zhourui , Song Simin , Cheng Liming , Zhu Rongrong 
Published: May 2021

AbstractThe differentiation of neural stem cells (NSCs) into neurons is proposed to be critical in devising potential cell-based therapeutic strategies for central nervous system (CNS) diseases, however, the determination and prediction of differentiation is complex and not yet clearly established, especially at the early stage. We hypothesize that deep learning could extract minutiae from large-scale datasets, and present a deep neural network model for predictable reliable identification of NSCs fate. Remarkably, using only bright field images without artificial labelling, our model is surprisingly effective at identifying the differentiated cell types, even as early as 1 day of culture. Moreover, our approach showcases superior precision and robustness in designed independent test scenarios involving various inducers, including neurotrophins, hormones, small molecule compounds and even nanoparticles, suggesting excellent generalizability and applicability. We anticipate that our accurate and robust deep learning-based platform for NSCs differentiation identification will accelerate the progress of NSCs applications.
Inner hair cell stereocilia are embedded in the tectorial membrane
Authors: Hakizimana Pierre , Fridberger Anders 
Published: May 2021

AbstractMammalian hearing depends on sound-evoked displacements of the stereocilia of inner hair cells (IHCs), which cause the endogenous mechanoelectrical transducer channels to conduct inward currents of cations including Ca2+. Due to their presumed lack of contacts with the overlaying tectorial membrane (TM), the putative stimulation mechanism for these stereocilia is by means of the viscous drag of the surrounding endolymph. However, despite numerous efforts to characterize the TM by electron microscopy and other techniques, the exact IHC stereocilia-TM relationship remains elusive. Here we show that Ca2+-rich filamentous structures, that we call Ca2+ ducts, connect the TM to the IHC stereocilia to enable mechanical stimulation by the TM while also ensuring the stereocilia access to TM Ca2+. Our results call for a reassessment of the stimulation mechanism for the IHC stereocilia and the TM role in hearing.
Allopurinol ameliorates high fructose diet induced hepatic steatosis in diabetic rats through modulation of lipid metabolism, inflammation, and ER stress pathway
Authors: Cho In-Jin , Oh Da-Hee , Yoo Jin , Hwang You-Cheol , Ahn Kyu Jeung , Chung Ho-Yeon , Jeong Soung Won , Moon Ju-Young , Lee Sang-Ho , Lim Sung-Jig , Jeong In-Kyung 
Published: May 2021

AbstractExcess fructose consumption contributes to development obesity, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD). Uric acid (UA), a metabolite of fructose metabolism, may have a direct role in development of NAFLD, with unclear mechanism. This study aimed to evaluate role of fructose and UA in NAFLD and explore mechanisms of allopurinol (Allo, a UA lowering medication) on NAFLD in Otsuka Long-Evans Tokushima Fatty (OLETF) rats fed a high fructose diet (HFrD), with Long-Evans Tokushima Otsuka (LETO) rats used as a control. There were six groups: LETO, LETO-Allo, OLETF, OLETF-Allo, OLETF-HFrD, and OLETF-HFrD-Allo. HFrD significantly increased body weight, epididymal fat weight, and serum concentrations of UA, cholesterol, triglyceride, HbA1c, hepatic enzymes, HOMA-IR, fasting insulin, and two hour-glucose after intraperitoneal glucose tolerance tests, as well as NAFLD activity score of liver, compared to the OLETF group. Allopurinol treatment significantly reduced hepatic steatosis, epididymal fat, serum UA, HOMA-IR, hepatic enzyme levels, and cholesterol in the OLETF-HFrD-Allo group. Additionally, allopurinol significantly downregulated expression of lipogenic genes, upregulated lipid oxidation genes, downregulated hepatic pro-inflammatory cytokine genes, and decreased ER-stress induced protein expression, in comparison with the OLETF-HFrD group. In conclusion, allopurinol ameliorates HFrD-induced hepatic steatosis through modulation of hepatic lipid metabolism, inflammation, and ER stress pathway. UA may have a direct role in development of fructose-induced hepatic steatosis, and allopurinol could be a candidate for prevention or treatment of NAFLD.
Figla promotes secondary follicle growth in mature mice
Authors: Okunomiya Asuka , Horie Akihito , Tani Hirohiko , Sato Yukiyasu , Takamatsu Shiro , Brown J. B. , Sugimoto Miki , Hamanishi Junzo , Kondoh Eiji , Matsumura Noriomi , Mandai Masaki 
Published: May 2021

AbstractThe in vitro growth (IVG) of human follicles is a potential fertility option for women for whom cryopreserved ovarian tissues cannot be transplanted due to the risk of cancer cell reintroduction; however, there is currently no established method. Furthermore, optimal IVG conditions may differ between the follicles of adult and pre-pubertal females due to molecular differences suggested by basic research. To systematically identify differences between the secondary follicles of adult and pre-pubertal females, a comparative transcriptomic study using mice was conducted herein. Among differentially expressed genes (DEGs), Figla was up-regulated in mature mice. We successfully down-regulated Figla expression in secondary follicle oocytes by a Figla siRNA microinjection, and the subsequent IVG of follicles showed that the diameter of these follicles was smaller than those of controls in mature mice, whereas no significant difference was observed in premature mice. The canonical pathways of DEGs between control and Figla-reduced secondary follicles suggest that Figla up-regulates VDR/RXR activation and down-regulates stem cell pluripotency as well as estrogen signaling. We demonstrated for the first time that folliculogenesis of the secondary follicles of premature and mature mice may be regulated by different factors, such as Figla with its possible target genes, providing insights into optimal IVG conditions for adult and pre-pubertal females, respectively.