bluuebunny/crossref_metadata_2025_split huggingface dataset:
Succinylation-dependent mitochondrial translocation of PKM2 promotes cell survival in response to nutritional stress
Authors: Qi Hailong , Ning Xianling , Yu Chang , Ji Xin , Jin Yan , McNutt Michael A. , Yin Yuxin 
Published: February 2019

AbstractTumor growth and progression is characteristically associated with the synergistic effects of uncontrolled cellular proliferation and cell survival under stress. Pyruvate kinase M2 (PKM2) contributes to both of these effects. However, the specific mechanism by which PKM2 promotes uncontrolled proliferation or cell survival under stress in different nutritional environments is unclear. We show that succinylation mediated mitochondrial translocation of PKM2 under glucose starvation plays a role in switching the cellular machinery from proliferation to cell survival mode and vice versa. Mitochondrial PKM2 inhibits ubiquitination-mediated degradation of voltage-dependent anion channel 3 (VDAC3) and increases mitochondrial permeability to generate more ATP for cell survival under nutritional depletion. We found there is a positive correlation of upregulation of mitochondrial PKM2 and upregulation of VDAC3 in human colon cancer. This shows the mechanisms identified in this study in fact play a role in neoplastic biology. We therefore developed a small molecule designated compound 8 that blocks mitochondrial translocation of PKM2 and inhibits tumor development. Our data suggest that blocking PKM2 mitochondrial function with a small molecule inhibitor has potential for cancer treatment.
ZFP57 suppress proliferation of breast cancer cells through down-regulation of MEST-mediated Wnt/β-catenin signalling pathway
Authors: Chen Lie , Wu Xiaowei , Xie Hui , Yao Na , Xia Yiqin , Ma Ge , Qian Mengjia , Ge Han , Cui Yangyang , Huang Yue , Wang Shui , Zheng Mingjie 
Published: February 2019

AbstractActivation of oncogenes by promoter hypomethylation plays an important role in tumorigenesis. Zinc finger protein 57 (ZFP57), a member of KRAB-ZFPs, could maintain DNA methylation in embryonic stem cells (ESCs), although its role and underlying mechanisms in breast cancer are not well understood. In this study, we found that ZFP57 had low expression in breast cancer, and overexpression of ZFP57 could inhibit the proliferation of breast cancer cells by inhibiting the Wnt/β-catenin pathway. MEST was validated as the direct target gene of ZFP57 and MEST may be down-regulated by ZFP57 through conserving DNA methylation. Furthermore, overexpression of MEST could restore the tumour-suppressed and the Wnt/β-catenin pathway inactivated effects of ZFP57. ZFP57-MEST and the Wnt/β-catenin pathway axis are involved in breast tumorigenesis, which may represent a potential diagnostic biomarker, and provide a new insight into a novel therapeutic strategy for breast cancer patients.
circTADA2As suppress breast cancer progression and metastasis via targeting miR-203a-3p/SOCS3 axis
Authors: Xu Jian-Zhen , Shao Chang-Chun , Wang Xiao-Jia , Zhao Xing , Chen Jun-Qing , Ouyang Yan-Xiu , Feng Jun , Zhang Fan , Huang Wen-He , Ying Qian , Chen Chun-Fa , Wei Xiao-Long , Dong Hong-Yan , Zhang Guo-Jun , Chen Min 
Published: February 2019

AbstractMore and more evidence indicates that circular RNAs (circRNAs) have important roles in several diseases, especially in cancers. However, their involvement remains to be investigated in breast cancer. Through screening circRNA profile, we identified 235 differentially expressed circRNAs in breast cancer. Subsequently, we explored the clinical significance of two circTADA2As in a large cohort of triple-negative breast cancer (TNBC), and performed functional analysis of circTADA2A-E6 in vitro and in vivo to support clinical findings. Finally, we evaluated the effect of circTADA2A-E6 on miR-203a-3p and its target gene SOCS3. We detected two circRNAs, circTADA2A-E6 and circTADA2A-E5/E6, which were among the top five differentially expressed circRNAs in breast cancer. They were consistently and significantly decreased in a large cohort of breast cancer patients, and their downregulation was associated with poor patient survival for TNBC. Especially, circTADA2A-E6 suppressed in vitro cell proliferation, migration, invasion, and clonogenicity and possessed tumor-suppressor capability. circTADA2A-E6 preferentially acted as a miR-203a-3p sponge to restore the expression of miRNA target gene SOCS3, resulting in a less aggressive oncogenic phenotype. circTADA2As as promising prognostic biomarkers in TNBC patients, and therapeutic targeting of circTADA2As/miRNA/mRNA network may be a potential strategy for the treatment of breast cancer.
Microglia as modulators of exosomal alpha-synuclein transmission
Authors: Xia Yun , Zhang Guoxin , Han Chao , Ma Kai , Guo Xingfang , Wan Fang , Kou Liang , Yin Sijia , Liu Ling , Huang Jinsha , Xiong Nian , Wang Tao 
Published: February 2019

AbstractRecent researches regarding to exosomal involvement in alpha-synuclein (α-syn) transmission relating to the pathological process of Parkinson’s disease (PD) have attracted considerable attention. It is highly desirable to make clear the diffusion process and cellular uptake of α-syn-associated exosomes and the underlying mechanism of exosomes-involved communication in the synucleinopathy pathogenesis. To determine the contribution of α-syn-associated exosomes to the initiation and progression of PD, plasma exosomes derived from PD patients were stereotaxically injected into the striatum of mice brains. Exosomes extracted from plasma diagnosed with PD contained monomeric and oligomeric α-syn. Here, we found that microglia display a high potency for uptake of plasma exosomes derived from PD patients, and therefore could be activated by exogenous exosomes in vitro and in vivo. In addition, immunofluorescent double staining verified the transfer of exogenous human exosomal α-syn to neurons. The release of human exosomal α-syn from microglia may facilitate this propagation. Finally, we described a mechanism underlying this potential role of microglia in the transmission of exosomal α-syn. Specifically, exogenous exosomes were found to dysregulate autophagy of the BV2 mouse microglia cell line with presentation of increased accumulation of intracellular α-syn and accelerated secretion of α-syn into extracellular space. These results suggest that microglia play a crucial role in the transmission of α-syn via exosomal pathways, in additional to idea that the progression of PD may be altered by the modulation of exosome secretion and/or microglial states.
m6A methylation controls pluripotency of porcine induced pluripotent stem cells by targeting SOCS3/JAK2/STAT3 pathway in a YTHDF1/YTHDF2-orchestrated manner
Authors: Wu Ruifan , Liu Youhua , Zhao Yuanling , Bi Zhen , Yao Yongxi , Liu Qing , Wang Fengqin , Wang Yizhen , Wang Xinxia 
Published: February 2019

AbstractEmbryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine, disease treatment, and organ transplantation. As the ethical issue of human ESCs and similarity of pig in human genome and physiological characteristics, the porcine iPSCs (piPSCs) have become an ideal alternative study model. N6-methyladenosine (m6A) methylation is the most prevalent modification in eukaryotic mRNAs, regulating the self-renewal and differentiation of pluripotency stem cells. However, the explicit m6A-regulating machinery remains controversial. Here, we demonstrate that m6A modification and its modulators play a crucial role in mediating piPSCs pluripotency. In brief, loss of METTL3 significantly impairs self-renewal and triggers differentiation of piPSCs by interfering JAK2 and SOCS3 expression, further inactivating JAK2–STAT3 pathway, which then blocks the transcription of KLF4 and SOX2. We identify that both of JAK2 and SOSC3 have m6A modification at 3′UTR by m6A-seq analysis. Dual-luciferase assay shows that METTL3 regulates JAK2 and SOCS3 expression in an m6A-dependent way. RIP-qPCR validates JAK2 and SOCS3 are the targets of YTHDF1 and YTHDF2, respectively. SiMETTL3 induced lower m6A levels of JAK2 and SOCS3 lead to the inhibition of YTHDF1-mediated JAK2 translation and the block of YTHDF2-dependent SOCS3 mRNA decay. Subsequently, the altered protein expressions of JAK2 and SOCS3 inhibit JAK2–STAT3 pathway and then the pluripotency of piPSCs. Collectively, our work uncovers the critical role of m6A modification and its modulators in regulating piPSCs pluripotency and provides insight into an orchestrated network linking the m6A methylation and SOCS3/JAK2/STAT3 pathway in pluripotency regulation.
Single gyroid-structured metallic nanoporous spheres fabricated from double gyroid-forming block copolymers via templated electroless plating
Authors: Yang Kai-Chieh , Yao Cheng-Thai , Huang Liang-Yu , Tsai Jing-Cherng , Hung Wei-Song , Hsueh Han-Yu , Ho Rong-Ming 
Published: February 2019

AbstractHerein, we suggest a methodology for the fabrication of well-defined metallic nanoporous spheres with single gyroid (SG) structure by simply using self-assembled diblock copolymer with double gyroid (DG) structure as a template for electroless plating. Note that owing to the consideration of thermodynamic stability, the self-assembly of diblock copolymers gives rise to a DG phase instead of an SG phase. By controlling the nucleus density for the reduction of Pd ions within the diblock copolymer template, SG-structured Ni can be easily fabricated through the nucleation and growth processes. Consequently, nanoporous Ni spheres with uniform pore sizes and high specific surface areas can be fabricated. Moreover, nanoporous Ni spheres with controlled microscale particle sizes can thus be obtained by controlling the reduction time for the growth of Ni, which enables the feasibility of recyclability via magnetic fields. The combination of structural and morphological characteristics of the fabricated nanoporous Ni spheres make them appealing for use in a wide variety of applications, such as high-efficiency and well selectivity hydrogenation catalysts with recyclability due to their narrow pore size distributions, high specific surface areas, 3D curved surfaces, and controlled microscale particle sizes.
High capacity silicon anodes enabled by MXene viscous aqueous ink
Authors: Zhang Chuanfang , Park Sang-Hoon , Seral‐Ascaso Andrés , Barwich Sebastian , McEvoy Niall , Boland Conor S. , Coleman Jonathan N. , Gogotsi Yury , Nicolosi Valeria 
Published: February 2019

AbstractThe ever-increasing demands for advanced lithium-ion batteries have greatly stimulated the quest for robust electrodes with a high areal capacity. Producing thick electrodes from a high-performance active material would maximize this parameter. However, above a critical thickness, solution-processed films typically encounter electrical/mechanical problems, limiting the achievable areal capacity and rate performance as a result. Herein, we show that two-dimensional titanium carbide or carbonitride nanosheets, known as MXenes, can be used as a conductive binder for silicon electrodes produced by a simple and scalable slurry-casting technique without the need of any other additives. The nanosheets form a continuous metallic network, enable fast charge transport and provide good mechanical reinforcement for the thick electrode (up to 450 µm). Consequently, very high areal capacity anodes (up to 23.3 mAh cm−2) have been demonstrated.
Role of cyclooxygenase-2-mediated prostaglandin E2-prostaglandin E receptor 4 signaling in cardiac reprogramming
Authors: Muraoka Naoto , Nara Kaori , Tamura Fumiya , Kojima Hidenori , Yamakawa Hiroyuki , Sadahiro Taketaro , Miyamoto Kazutaka , Isomi Mari , Haginiwa Sho , Tani Hidenori , Kurotsu Shota , Osakabe Rina , Torii Satoru , Shimizu Shigeomi , Okano Hideyuki , Sugimoto Yukihiko , Fukuda Keiichi , Ieda Masaki 
Published: February 2019

AbstractDirect cardiac reprogramming from fibroblasts can be a promising approach for disease modeling, drug screening, and cardiac regeneration in pediatric and adult patients. However, postnatal and adult fibroblasts are less efficient for reprogramming compared with embryonic fibroblasts, and barriers to cardiac reprogramming associated with aging remain undetermined. In this study, we screened 8400 chemical compounds and found that diclofenac sodium (diclofenac), a non-steroidal anti-inflammatory drug, greatly enhanced cardiac reprogramming in combination with Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Hand2. Intriguingly, diclofenac promoted cardiac reprogramming in mouse postnatal and adult tail-tip fibroblasts (TTFs), but not in mouse embryonic fibroblasts (MEFs). Mechanistically, diclofenac enhanced cardiac reprogramming by inhibiting cyclooxygenase-2, prostaglandin E2/prostaglandin E receptor 4, cyclic AMP/protein kinase A, and interleukin 1β signaling and by silencing inflammatory and fibroblast programs, which were activated in postnatal and adult TTFs. Thus, anti-inflammation represents a new target for cardiac reprogramming associated with aging.
Targeting MC1R depalmitoylation to prevent melanomagenesis in redheads
Authors: Chen Shuyang , Han Changpeng , Miao Xiao , Li Xin , Yin Chengqian , Zou Junrong , Liu Min , Li Shanshan , Stawski Lukasz , Zhu Bo , Shi Qiong , Xu Zhi-Xiang , Li Chunying , Goding Colin R. , Zhou Jun , Cui Rutao 
Published: February 2019

AbstractSome genetic melanocortin-1 receptor (MC1R) variants responsible for human red hair color (RHC-variants) are consequently associated with increased melanoma risk. Although MC1R signaling is critically dependent on its palmitoylation primarily mediated by the ZDHHC13 protein-acyl transferase, whether increasing MC1R palmitoylation represents a viable therapeutic target to limit melanomagenesis in redheads is unknown. Here we identify a specific and efficient in vivo strategy to induce MC1R palmitoylation for therapeutic benefit. We validate the importance of ZDHHC13 to MC1R signaling in vivo by targeted expression of ZDHHC13 in C57BL/6J-MC1RRHCmice and subsequently inhibit melanomagenesis. By identifying APT2 as the MC1R depalmitoylation enzyme, we are able to demonstrate that administration of the selective APT2 inhibitor ML349 treatment efficiently increases MC1R signaling and represses UVB-induced melanomagenesis in vitro and in vivo. Targeting APT2, therefore, represents a preventive/therapeutic strategy to reduce melanoma risk, especially in individuals with red hair.
Negative dielectric constant of water confined in nanosheets
Authors: Sugahara Akira , Ando Yasunobu , Kajiyama Satoshi , Yazawa Koji , Gotoh Kazuma , Otani Minoru , Okubo Masashi , Yamada Atsuo 
Published: February 2019

AbstractElectric double-layer capacitors are efficient energy storage devices that have the potential to account for uneven power demand in sustainable energy systems. Earlier attempts to improve an unsatisfactory capacitance of electric double-layer capacitors have focused on meso- or nanostructuring to increase the accessible surface area and minimize the distance between the adsorbed ions and the electrode. However, the dielectric constant of the electrolyte solvent embedded between adsorbed ions and the electrode surface, which also governs the capacitance, has not been previously exploited to manipulate the capacitance. Here we show that the capacitance of electric double-layer capacitor electrodes can be enlarged when the water molecules are strongly confined into the two-dimensional slits of titanium carbide MXene nanosheets. Using electrochemical methods and theoretical modeling, we find that dipolar polarization of strongly confined water resonantly overscreens an external electric field and enhances capacitance with a characteristically negative dielectric constant of a water molecule.
A sequestered fusion peptide in the structure of an HIV-1 transmitted founder envelope trimer
Authors: Ananthaswamy Neeti , Fang Qianglin , AlSalmi Wadad , Jain Swati , Chen Zhenguo , Klose Thomas , Sun Yingyuan , Liu Yue , Mahalingam Marthandan , Chand Subhash , Tovanabutra Sodsai , Robb Merlin L. , Rossmann Michael G. , Rao Venigalla B. 
Published: February 2019

AbstractThe envelope protein of human immunodeficiency virus-1 (HIV-1) and its fusion peptide are essential for cell entry and vaccine design. Here, we describe the 3.9-Å resolution structure of an envelope protein trimer from a very early transmitted founder virus (CRF01_AE T/F100) complexed with Fab from the broadly neutralizing antibody (bNAb) 8ANC195. The overall T/F100 trimer structure is similar to other reported “closed” state prefusion trimer structures. In contrast, the fusion peptide, which is exposed to solvent in reported closed structures, is sequestered (buried) in the hydrophobic core of the T/F100 trimer. A buried conformation has previously been observed in “open” state structures formed after CD4 receptor binding. The T/F100 trimer binds poorly to bNAbs including the fusion peptide-specific bNAbs PGT151 and VRC34.01. The T/F100 structure might represent a prefusion state, intermediate between the closed and open states. These observations are relevant to mechanisms of HIV-1 transmission and vaccine design.
Orthobunyavirus spike architecture and recognition by neutralizing antibodies
Authors: Hellert Jan , Aebischer Andrea , Wernike Kerstin , Haouz Ahmed , Brocchi Emiliana , Reiche Sven , Guardado-Calvo Pablo , Beer Martin , Rey Félix A. 
Published: February 2019

AbstractOrthobunyaviruses (OBVs) form a distinct genus of arthropod-borne bunyaviruses that can cause severe disease upon zoonotic transmission to humans. Antigenic drift or genome segment re-assortment have in the past resulted in new pathogenic OBVs, making them potential candidates for causing emerging zoonoses in the future. Low-resolution electron cryo-tomography studies have shown that OBV particles feature prominent trimeric spikes, but their molecular organization remained unknown. Here we report X-ray crystallography studies of four different OBVs showing that the spikes are formed by an N-terminal extension of the fusion glycoprotein Gc. Using Schmallenberg virus, a recently emerged OBV, we also show that the projecting spike is the major target of the neutralizing antibody response, and provide X-ray structures in complex with two protecting antibodies. We further show that immunization of mice with the spike domains elicits virtually sterilizing immunity, providing fundamental knowledge essential in the preparation for potential newly emerging OBV zoonoses.
A silicon-on-insulator slab for topological valley transport
Authors: He Xin-Tao , Liang En-Tao , Yuan Jia-Jun , Qiu Hao-Yang , Chen Xiao-Dong , Zhao Fu-Li , Dong Jian-Wen 
Published: February 2019

AbstractBackscattering suppression in silicon-on-insulator (SOI) is one of the central issues to reduce energy loss and signal distortion, enabling for capability improvement of modern information processing systems. Valley physics provides an intriguing way for robust information transfer and unidirectional coupling in topological nanophotonics. Here we realize topological transport in a SOI valley photonic crystal slab. Localized Berry curvature near zone corners guarantees the existence of valley-dependent edge states below light cone, maintaining in-plane robustness and light confinement simultaneously. Topologically robust transport at telecommunication is observed along two sharp-bend interfaces in subwavelength scale, showing flat-top high transmission of ~10% bandwidth. Topological photonic routing is achieved in a bearded-stack interface, due to unidirectional excitation of valley-chirality-locked edge state from the phase vortex of a nanoscale microdisk. These findings show the prototype of robustly integrated devices, and open a new door towards the observation of non-trivial states even in non-Hermitian systems.
Charged grain boundary transitions in ionic ceramics for energy applications
Authors: Vikrant K. S. N. , García R. Edwin 
Published: February 2019

AbstractSurfaces and interfaces in ionic ceramics play a pivotal role in defining the transport limitations in many of the existing and emerging applications in energy-related systems such as fuel cells, rechargeable batteries, as well as advanced electronics such as those found in semiconducting, ferroelectric, and piezotronic applications. Here, a variational framework has been developed to understand the effects of the intrinsic and extrinsic ionic species and point defects on the structural and electrochemical stability of grain boundaries in polycrystalline ceramics. The theory predicts the conditions for the interfacial electrochemical and structural stability and phase transitions of charged interfaces and quantifies the properties induced by the broad region of electrochemical influence in front of a grain boundary capable of spanning anywhere from a few angtroms to entire grains. We demonstrate the validity of this theory for YxZr1−xO2−x/2, cubic yttria stabilized zirconia. For small crystallographic misorientations, sharp Debye-type interfaces, D(1):$${\mathrm{C}}^{VY}{\mathrm{S}}^{\underline {VY} }$$

C

V
Y

S

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Y

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, are favored and promote high ionic conductivity in materials in polycrystalline form. For large grain boundary misorientations and large amounts of [Y2O3] substitutions, three Mott–Schottky interfaces, MS(2):$${\mathrm{C}}^{VY\,\underline h e}{\mathrm{S}}^{\underline {VYh} e}$$

C

V
Y

h

̲

e

S

V
Y
h

̲

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, MS(2):$${\mathrm{C}}^{VY\underline h e}{\mathrm{S}}^{e\underline {hVY} }$$

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Y

h

̲

e

S

e

h
V
Y

̲

, and MS(2):$${\mathrm{C}}^{VY}{\mathrm{S}}^{\underline h e}$$

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Y

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are responsible for controlling grain boundary segregation and the observed poor macroscopic ionic transport, in great agreement with the scientific literature.
Electron engineering of metallic multiferroic polarons in epitaxial BaTiO3
Authors: Xu Tao , Shimada Takahiro , Araki Yasumitsu , Mori Masataka , Fujimoto Gen , Wang Jie , Zhang Tong-Yi , Kitamura Takayuki 
Published: February 2019

AbstractThe coexistence of ferroelectricity, conductivity, and magnetism in a single-phase material has attracted considerable attention due to fundamental interest and tremendous technological potential. However, their mutually exclusive mechanisms hinder the discovery of multifunctional conducting multiferroics. Here, we propose a new material design approach for electron engineering to enable these conflicting properties to coexist. We use first principles calculations to demonstrate that appropriate mechanical strain can turn the excess electrons in doped BaTiO3 from a free-carrier configuration to a localized polaronic state by modulating the electron–phonon coupling. The resulting localized spin-polarized electron survives the host ferroelectricity and consequently manifests as a multiferroic polaron. The multiferroic properties coexist with the electronic conductivity arising from the high-hopping mobility of the polaron, which enables the doped epitaxial BaTiO3 to act as a multiferroic conducting material. This mechanical control over the electron configuration is a potential path toward unusual coexisting properties.