bluuebunny/crossref_metadata_2025_split huggingface dataset:
miRNA-3473b contributes to neuroinflammation following cerebral ischemia
Authors: Wang Xiaoyu , Chen Shuangshuang , Ni Jingshu , Cheng Jian , Jia Jia , Zhen Xuechu 
Published: January 2018

AbstractMicroRNAs play an essential role in stroke pathology. Here, we investigated the role of a newly identified microRNA, miR-3473b, in stroke pathology. The expression of miR-3473b was upregulated in the cortex and striatum in mice following transient middle cerebral artery occlusion (MCAO). Intracerebroventricular injection of the miR-3473b antagomir prior to MCAO remarkably attenuated ischemia-induced expression of miR-3473b and pro-inflammatory factors in the ischemic brain and decreased infarct volumes in mice following MCAO. Using in vitro approaches, we showed that the miR-3473b antagomir reduced the mRNA and protein levels of pro-inflammatory factors (iNOS, COX-2, TNF-α, and IL-6) in BV2 microglial cells subjected to LPS stimulation. The miR-3473b antagomir also decreased the expression of pro-inflammatory factors in BV2 cells activated with conditioned medium collected from oxygen-glucose deprivation (OGD)-treated neurons. Suppressor of cytokine signaling 3 (SOCS3), a physiological regulator of innate and adaptive immunity, was predicted to be a potential target of miR-3473b. We verified that the miR-3473b mimic decreased SOCS3 expression in BV2 cells. Meanwhile, the miR-3473b antagomir significantly increased both SOCS3 mRNA and protein levels in the BV2 cells treated with LPS as well as in the ischemic brain. By using the dual luciferase assay, we further showed that the 3′-untranslational region of SOCS3 was directly targeted by miR-3473b. In conclusion, induction of miR-3473b, which is likely targeted to SOCS3, contributes to stroke pathogenesis by enhancing post-stroke neuroinflammation injury.
NF-κB/miR-223-3p/ARID1A axis is involved in Helicobacter pylori CagA-induced gastric carcinogenesis and progression
Authors: Yang Fenghua , Xu Yugang , Liu Chao , Ma Cunying , Zou Shuiyan , Xu Xia , Jia Jihui , Liu Zhifang 
Published: January 2018

AbstractInfection with Helicobacter pylori (H. pylori) and the resulting gastric inflammation is regarded as the strongest risk factor for gastric carcinogenesis and progression. NF-κB plays an important role in linking H. pylori-mediated inflammation to cancer. However, the underlying mechanisms are poorly understood. In this study, we find that H. pylori infection induces miR-223-3p expression in H. pylori CagA-dependent manner. NF-κB stimulates miR-223-3p expression via directly binding to the promoter of miR-223-3p and is required for H. pylori CagA-mediated upregulation of miR-223-3p. miR-223-3p promotes the proliferation and migration of gastric cancer cells by directly targeting ARID1A and decreasing its expression. Furthermore, miR-223-3p/ARID1A axis is involved in CagA-induced cell proliferation and migration. In the clinical setting, the level of miR-223-3p is upregulated, while ARID1A is downregulated significantly in human gastric cancer tissues compared with the corresponding noncancerous tissues. The expression level of miR-223-3p is significantly higher in H. pylori-positive gastric cancer tissues than that in H. pylori-negative tissues. Moreover, a negative correlation between miR-223-3p and ARID1A expression is found in the gastric cancer tissues. Taken together, our findings suggested NF-κB/miR-223-3p/ARID1A axis may link the process of H. pylori-induced chronic inflammation to gastric cancer, thereby providing a new insight into the mechanism underlying H. pylori-associated gastric diseases.
Brain activity patterns in high-throughput electrophysiology screen predict both drug efficacies and side effects
Authors: Eimon Peter M. , Ghannad-Rezaie Mostafa , De Rienzo Gianluca , Allalou Amin , Wu Yuelong , Gao Mu , Roy Ambrish , Skolnick Jeffrey , Yanik Mehmet Fatih 
Published: January 2018

AbstractNeurological drugs are often associated with serious side effects, yet drug screens typically focus only on efficacy. We demonstrate a novel paradigm utilizing high-throughput in vivo electrophysiology and brain activity patterns (BAPs). A platform with high sensitivity records local field potentials (LFPs) simultaneously from many zebrafish larvae over extended periods. We show that BAPs from larvae experiencing epileptic seizures or drug-induced side effects have substantially reduced complexity (entropy), similar to reduced LFP complexity observed in Parkinson’s disease. To determine whether drugs that enhance BAP complexity produces positive outcomes, we used light pulses to trigger seizures in a model of Dravet syndrome, an intractable genetic epilepsy. The highest-ranked compounds identified by BAP analysis exhibit far greater anti-seizure efficacy and fewer side effects during subsequent in-depth behavioral assessment. This high correlation with behavioral outcomes illustrates the power of brain activity pattern-based screens and identifies novel therapeutic candidates with minimal side effects.
Stratospheric ozone loss over the Eurasian continent induced by the polar vortex shift
Authors: Zhang Jiankai , Tian Wenshou , Xie Fei , Chipperfield Martyn P. , Feng Wuhu , Son Seok-Woo , Abraham N. Luke , Archibald Alexander T. , Bekki Slimane , Butchart Neal , Deushi Makoto , Dhomse Sandip , Han Yuanyuan , Jöckel Patrick , Kinnison Douglas , Kirner Ole , Michou Martine , Morgenstern Olaf , O’Connor Fiona M. , Pitari Giovanni , Plummer David A. , Revell Laura E. , Rozanov Eugene , Visioni Daniele , Wang Wuke , Zeng Guang 
Published: January 2018

AbstractThe Montreal Protocol has succeeded in limiting major ozone-depleting substance emissions, and consequently stratospheric ozone concentrations are expected to recover this century. However, there is a large uncertainty in the rate of regional ozone recovery in the Northern Hemisphere. Here we identify a Eurasia-North America dipole mode in the total column ozone over the Northern Hemisphere, showing negative and positive total column ozone anomaly centres over Eurasia and North America, respectively. The positive trend of this mode explains an enhanced total column ozone decline over the Eurasian continent in the past three decades, which is closely related to the polar vortex shift towards Eurasia. Multiple chemistry-climate-model simulations indicate that the positive Eurasia-North America dipole trend in late winter is likely to continue in the near future. Our findings suggest that the anticipated ozone recovery in late winter will be sensitive not only to the ozone-depleting substance decline but also to the polar vortex changes, and could be substantially delayed in some regions of the Northern Hemisphere extratropics.
Elucidating the genomic architecture of Asian EGFR-mutant lung adenocarcinoma through multi-region exome sequencing
Authors: Nahar Rahul , Zhai Weiwei , Zhang Tong , Takano Angela , Khng Alexis J. , Lee Yin Yeng , Liu Xingliang , Lim Chong Hee , Koh Tina P. T. , Aung Zaw Win , Lim Tony Kiat Hon , Veeravalli Lavanya , Yuan Ju , Teo Audrey S. M. , Chan Cheryl X. , Poh Huay Mei , Chua Ivan M. L. , Liew Audrey Ann , Lau Dawn Ping Xi , Kwang Xue Lin , Toh Chee Keong , Lim Wan-Teck , Lim Bing , Tam Wai Leong , Tan Eng-Huat , Hillmer Axel M. , Tan Daniel S. W. 
Published: January 2018

AbstractEGFR-mutant lung adenocarcinomas (LUAD) display diverse clinical trajectories and are characterized by rapid but short-lived responses to EGFR tyrosine kinase inhibitors (TKIs). Through sequencing of 79 spatially distinct regions from 16 early stage tumors, we show that despite low mutation burdens, EGFR-mutant Asian LUADs unexpectedly exhibit a complex genomic landscape with frequent and early whole-genome doubling, aneuploidy, and high clonal diversity. Multiple truncal alterations, including TP53 mutations and loss of CDKN2A and RB1, converge on cell cycle dysregulation, with late sector-specific high-amplitude amplifications and deletions that potentially beget drug resistant clones. We highlight the association between genomic architecture and clinical phenotypes, such as co-occurring truncal drivers and primary TKI resistance. Through comparative analysis with published smoking-related LUAD, we postulate that the high intra-tumor heterogeneity observed in Asian EGFR-mutant LUAD may be contributed by an early dominant driver, genomic instability, and low background mutation rates.
AICDA drives epigenetic heterogeneity and accelerates germinal center-derived lymphomagenesis
Authors: Teater Matt , Dominguez Pilar M. , Redmond David , Chen Zhengming , Ennishi Daisuke , Scott David W. , Cimmino Luisa , Ghione Paola , Chaudhuri Jayanta , Gascoyne Randy D. , Aifantis Iannis , Inghirami Giorgio , Elemento Olivier , Melnick Ari , Shaknovich Rita 
Published: January 2018

AbstractEpigenetic heterogeneity is emerging as a feature of tumors. In diffuse large B-cell lymphoma (DLBCL), increased cytosine methylation heterogeneity is associated with poor clinical outcome, yet the underlying mechanisms remain unclear. Activation-induced cytidine deaminase (AICDA), an enzyme that mediates affinity maturation and facilitates DNA demethylation in germinal center (GC) B cells, is required for DLBCL pathogenesis and linked to inferior outcome. Here we show that AICDA overexpression causes more aggressive disease in BCL2-driven murine lymphomas. This phenotype is associated with increased cytosine methylation heterogeneity, but not with increased AICDA-mediated somatic mutation burden. Reciprocally, the cytosine methylation heterogeneity characteristic of normal GC B cells is lost upon AICDA depletion. These observations are relevant to human patients, since DLBCLs with high AICDA expression manifest increased methylation heterogeneity vs. AICDA-low DLBCLs. Our results identify AICDA as a driver of epigenetic heterogeneity in B-cell lymphomas with potential significance for other tumors with aberrant expression of cytidine deaminases.
Heliconical smectic phases formed by achiral molecules
Authors: Abberley Jordan P. , Killah Ross , Walker Rebecca , Storey John M. D. , Imrie Corrie T. , Salamończyk Mirosław , Zhu Chenhui , Gorecka Ewa , Pociecha Damian 
Published: January 2018

AbstractChiral symmetry breaking in soft matter is a hot topic of current research. Recently, such a phenomenon was found in a fluidic phase showing orientational order of molecules—the nematic phase; although built of achiral molecules, the phase can exhibit structural chirality—average molecular direction follows a short-pitch helix. Here, we report a series of achiral asymmetric dimers with an odd number of atoms in the spacer, which form twisted structures in nematic as well as in lamellar phases. The tight pitch heliconical nematic (NTB) phase and heliconical tilted smectic C (SmCTB) phase are formed. The formation of a variety of helical structures is accompanied by a gradual freezing of molecular rotation. In the lowest temperature smectic phase, HexI, the twist is expressed through the formation of hierarchical structure: nanoscale helices and mesoscopic helical filaments. The short-pitch helical structure in the smectic phases is confirmed by resonant X-ray measurements.
Raman enhancement on ultra-clean graphene quantum dots produced by quasi-equilibrium plasma-enhanced chemical vapor deposition
Authors: Liu Donghua , Chen Xiaosong , Hu Yibin , Sun Tai , Song Zhibo , Zheng Yujie , Cao Yongbin , Cai Zhi , Cao Min , Peng Lan , Huang Yuli , Du Lei , Yang Wuli , Chen Gang , Wei Dapeng , Wee Andrew Thye Shen , Wei Dacheng 
Published: January 2018

AbstractGraphene is regarded as a potential surface-enhanced Raman spectroscopy (SERS) substrate. However, the application of graphene quantum dots (GQDs) has had limited success due to material quality. Here, we develop a quasi-equilibrium plasma-enhanced chemical vapor deposition method to produce high-quality ultra-clean GQDs with sizes down to 2 nm directly on SiO2/Si, which are used as SERS substrates. The enhancement factor, which depends on the GQD size, is higher than conventional graphene sheets with sensitivity down to 1 × 10−9 mol L−1 rhodamine. This is attributed to the high-quality GQDs with atomically clean surfaces and large number of edges, as well as the enhanced charge transfer between molecules and GQDs with appropriate diameters due to the existence of Van Hove singularities in the electronic density of states. This work demonstrates a sensitive SERS substrate, and is valuable for applications of GQDs in graphene-based photonics and optoelectronics.
Phosphorylation-induced conformation of β2-adrenoceptor related to arrestin recruitment revealed by NMR
Authors: Shiraishi Yutaro , Natsume Mei , Kofuku Yutaka , Imai Shunsuke , Nakata Kunio , Mizukoshi Toshimi , Ueda Takumi , Iwaï Hideo , Shimada Ichio 
Published: January 2018

AbstractThe C-terminal region of G-protein-coupled receptors (GPCRs), stimulated by agonist binding, is phosphorylated by GPCR kinases, and the phosphorylated GPCRs bind to arrestin, leading to the cellular responses. To understand the mechanism underlying the formation of the phosphorylated GPCR-arrestin complex, we performed NMR analyses of the phosphorylated β2-adrenoceptor (β2AR) and the phosphorylated β2AR–β-arrestin 1 complex, in the lipid bilayers of nanodisc. Here we show that the phosphorylated C-terminal region adheres to either the intracellular side of the transmembrane region or lipids, and that the phosphorylation of the C-terminal region allosterically alters the conformation around M2155.54 and M2796.41, located on transemembrane helices 5 and 6, respectively. In addition, we found that the conformation induced by the phosphorylation is similar to that corresponding to the β-arrestin-bound state. The phosphorylation-induced structures revealed in this study propose a conserved structural motif of GPCRs that enables β-arrestin to recognize dozens of GPCRs.
Abnormal phase transition between two-dimensional high-density liquid crystal and low-density crystalline solid phases
Authors: Li Wenbin , Kong Longjuan , Feng Baojie , Fu Huixia , Li Hui , Zeng Xiao Cheng , Wu Kehui , Chen Lan 
Published: January 2018

AbstractSome two-dimensional liquid systems are theoretically predicted to have an anomalous phase transition due to unique intermolecular interactions, for example the first-order transition between two-dimensional high-density water and low-density amorphous ice. However, it has never been experimentally observed, to the best of our knowledge. Here we report an entropy-driven phase transition between a high-density liquid crystal and low-density crystalline solid, directly observed by scanning tunneling microscope in carbon monoxide adsorbed on Cu(111). Combined with first principle calculations, we find that repulsive dipole–dipole interactions between carbon monoxide molecules lead to unconventional thermodynamics. This finding of unconventional thermodynamics in two-dimensional carbon monoxide not only provides a platform to study the fundamental principles of anomalous phase transitions in two-dimensional liquids at the atomic scale, but may also help to design and develop more efficient copper-based catalysis.
Au@Nb@H
x
K1-xNbO3 nanopeapods with near-infrared active plasmonic hot-electron injection for water splitting
Authors: Chen Ying-Chu , Hsu Yu-Kuei , Popescu Radian , Gerthsen Dagmar , Lin Yan-Gu , Feldmann Claus 
Published: January 2018

AbstractFull-spectrum utilization of diffusive solar energy by a photocatalyst for environmental remediation and fuel generation has long been pursued. In contrast to tremendous efforts in the UV-to-VIS light regime of the solar spectrum, the NIR and IR areas have been barely addressed although they represent about 50% of the solar flux. Here we put forward a biomimetic photocatalyst blueprint that emulates the growth pattern of a natural plant—a peapod—to address this issue. This design is exemplified via unidirectionally seeding core-shell Au@Nb nanoparticles in the cavity of semiconducting H
x
K1−xNbO3 nanoscrolls. The biomimicry of this nanopeapod (NPP) configuration promotes near-field plasmon–plasmon coupling between bimetallic Au@Nb nanoantennas (the peas), endowing the UV-active H
x
K1−xNbO3 semiconductor (the pods) with strong VIS and NIR light harvesting abilities. Moreover, the characteristic 3D metal-semiconductor junction of the Au@Nb@H
x
K1−xNbO3 NPPs favors the transfer of plasmonic hot carriers to trigger dye photodegradation and water photoelectrolysis as proofs-of-concept. Such broadband solar spectral response renders the Au@Nb@H
x
K1−xNbO3 NPPs highly promising for widespread photoactive devices.
Deubiquitinase USP13 dictates MCL1 stability and sensitivity to BH3 mimetic inhibitors
Authors: Zhang Shengzhe , Zhang Meiying , Jing Ying , Yin Xia , Ma Pengfei , Zhang Zhenfeng , Wang Xiaojie , Di Wen , Zhuang Guanglei 
Published: January 2018

AbstractMCL1 is a pivot member of the anti-apoptotic BCL-2 family proteins. While a distinctive feature of MCL1 resides in its efficient ubiquitination and destruction, the deubiquitinase USP9X has been implicated in the preservation of MCL1 expression by removing the polyubiquitin chains. Here we perform an unbiased siRNA screen and identify that the second deubiquitinase, USP13, regulates MCL1 stability in lung and ovarian cancer cells. Mechanistically, USP13 interacts with and stabilizes MCL1 via deubiquitination. As a result, USP13 depletion using CRISPR/Cas9 nuclease system inhibits tumor growth in xenografted nude mice. We further report that genetic or pharmacological inhibition of USP13 considerably reduces MCL1 protein abundance and significantly increases tumor cell sensitivity to BH3 mimetic inhibitors targeting BCL-2 and BCL-XL. Collectively, we nominate USP13 as a novel deubiquitinase which regulates MCL1 turnover in diverse solid tumors and propose that USP13 may be a potential therapeutic target for the treatment of various malignancies.
Relationship between spectrotemporal modulation detection and music perception in normal-hearing, hearing-impaired, and cochlear implant listeners
Authors: Choi Ji Eun , Won Jong Ho , Kim Cheol Hee , Cho Yang-Sun , Hong Sung Hwa , Moon Il Joon 
Published: January 2018

AbstractThe objective of this study was to examine the relationship between spectrotemporal modulation (STM) sensitivity and the ability to perceive music. Ten normal-hearing (NH) listeners, ten hearing aid (HA) users with moderate hearing loss, and ten cochlear Implant (CI) users participated in this study. Three different types of psychoacoustic tests including spectral modulation detection (SMD), temporal modulation detection (TMD), and STM were administered. Performances on these psychoacoustic tests were compared to music perception abilities. In addition, psychoacoustic mechanisms involved in the improvement of music perception through HA were evaluated. Music perception abilities in unaided and aided conditions were measured for HA users. After that, HA benefit for music perception was correlated with aided psychoacoustic performance. STM detection study showed that a combination of spectral and temporal modulation cues were more strongly correlated with music perception abilities than spectral or temporal modulation cues measured separately. No correlation was found between music perception performance and SMD threshold or TMD threshold in each group. Also, HA benefits for melody and timbre identification were significantly correlated with a combination of spectral and temporal envelope cues though HA.
Grey and white matter volumes either in treatment-naïve or hormone-treated transgender women: a voxel-based morphometry study
Authors: Spizzirri Giancarlo , Duran Fábio Luis Souza , Chaim-Avancini Tiffany Moukbel , Serpa Mauricio Henriques , Cavallet Mikael , Pereira Carla Maria Abreu , Santos Pedro Paim , Squarzoni Paula , da Costa Naomi Antunes , Busatto Geraldo F. , Abdo Carmita Helena Najjar 
Published: January 2018

AbstractMany previous magnetic resonance imaging (MRI) studies have documented sex differences in brain morphology, but the patterns of sexual brain differences in transgender women – male sex assigned at birth – with a diagnosis of gender dysphoria (TW) have been rarely investigated to date. We acquired T1-weighted MRI data for the following four (n = 80) groups: treatment-naïve TW (TNTW), TW treated with cross-sex hormones for at least one year (TTW), cisgender men, and cisgender women (cisgender individuals as controls). Differences in whole-brain and regional white matter volume and grey matter volume (GMV) were assessed using voxel-based morphometry. We found lower global brain volumes and regional GMVs in a large portion of the posterior-superior frontal cortex in the cisgender women group than in the TTW and cisgender men groups. Additionally, both transgender groups exhibited lower bilateral insular GMVs than the cisgender women group. Our results highlight differences in the insula in both transgender groups; such differences may be characteristic of TW. Furthermore, these alterations in the insula could be related to the neural network of body perception and reflect the distress that accompanies gender dysphoria.
Lamina Cribrosa Morphology Predicts Progressive Retinal Nerve Fiber Layer Loss In Eyes with Suspected Glaucoma
Authors: Kim Jeong-Ah , Kim Tae-Woo , Weinreb Robert N. , Lee Eun Ji , Girard Michaël J. A. , Mari Jean Martial 
Published: January 2018

AbstractAlthough early diagnosis and treatment reduce the risk of blindness from glaucoma, the decision on whether or not to begin treatment in patients with suspected glaucoma is often a dilemma because the majority of patients never develop definite glaucoma. A growing body of evidences suggests that posterior bowing of the lamina cribrosa (LC) is the earliest structural change preceding the retinal nerve fiber layer (RNFL) loss in glaucomatous optic neuropathy. Based on this notion, we conducted a prospective study enrolling 87 eyes suspected of having glaucoma to investigate whether the future rate of RNFL loss is associated with the baseline LC curve evaluated by measuring the LC curve index (LCCI) using enhanced depth imaging optical coherence tomography. A faster rate of RNFL loss was significantly associated with greater LCCI (P < 0.001;standardized coefficient beta = −0.392), older age (P = 0.008;beta = −0.314), and greater vertical cup-to-disc ratio (P = 0.040;beta = −0.233). Assessment of LC morphology may help predict the disease outcome in eyes with suspected glaucoma.
A Global View of Transcriptome Dynamics During Male Floral Bud Development in Populus tomentosa
Authors: Chen Zhong , Rao Pian , Yang Xiaoyu , Su Xiaoxing , Zhao Tianyun , Gao Kai , Yang Xiong , An Xinmin 
Published: January 2018

AbstractTo obtain a comprehensive overview of the dynamic transcriptome during male floral bud development in Populus tomentosa, high-throughput RNA-seq was conducted during eight flowering-related stages. Among the 109,212 de novo assembled unigenes, 6,959 were differentially expressed during the eight stages. The overrepresented classed of genes identified by Gene Ontology (GO) enrichment included ‘response to environmental stimuli’ and ‘plant-type spore development’. One-third of the differentially expressed genes were transcription factors (TFs). Several genes and gene families were analyzed in depth, including MADS-box TFs, Squamosa promoter binding protein-like family, receptor-like kinases, FLOWERING LOCUS T/TERMINAL-FLOWER-LIKE 1 family, key genes involved in anther and tapetum development, as well as LEAFY, WUSCHEL and CONSTANS. The results provided new insights into the roles of these and other well known gene families during the annual flowering cycle. To explore the mechanisms regulating poplar flowering, a weighted gene co-expression network was constructed using 98 floral-related genes involved in flower meristem identity and flower development. Many modules of co-expressed genes and hub genes were identified, such as APETALA1 and HUA1. This work provides many new insights on the annual flowering cycle in a perennial plant, and a major new resource for plant biology and biotechnology.