bluuebunny/crossref_metadata_2025_split huggingface dataset:
miR-539 acts as a tumor suppressor by targeting epidermal growth factor receptor in breast cancer
Authors: Guo Jilong , Gong Guohua , Zhang Bin 
Published: January 2018

AbstractBreast cancer is the most frequently diagnosed malignancy and the leading cause of cancer-associated death in women worldwide. microRNAs (miRNAs) play critical roles in the cellular processes of breast cancer. However, the crucial roles and underlying mechanisms of miR-539 in breast cancer remain unclear. By RT-qPCR, we found that expression of miR-539 was markedly down-regulated in breast cancer tissues and cell lines compared with that in paired adjacent normal tissues and normal cell lines. The low level of miR-539 expression was positively associated with lymph node metastasis. Furthermore, forced expression of miR-539 inhibited proliferation and migration of breast cancer MDA-MB-231 and MCF7 cells in vitro and suppressed tumor growth in vivo. Moreover, bioinformatics analysis and luciferase reporter assays indicated that epidermal growth factor receptor (EGFR) was a direct target of miR-539. Over-expression of miR-539 decreased the EGFR mRNA and protein levels in MDA-MB-231 and MCF7 cells. In addition, ectopic over-expression of EGFR partly reversed miR-539-inhibited proliferation as well as migration of MDA-MB-231 and MCF7 cells. Taken together, our results demonstrate that miR-539 functions as a tumor suppressor in breast cancer by downregulating EGFR, supporting the targeting of the novel miR-539/EGFR axis as a potentially effective therapeutic approach for breast cancer.
The fossil teeth of the Peking Man
Authors: Xing Song , Martinón-Torres María , Bermúdez de Castro José María 
Published: January 2018

AbstractThis study provides new original data, including the endostructure of most Zhoukoudian H. erectus teeth preserved to date, since the publication of Black in 1927 and Weidenreich in 1937. The new evidence ratifies the similarities of Zhoukoudian with other East Asian mid-Middle Pleistocene hominins such as Hexian and Yiyuan, and allows defining a dental pattern potentially characteristic of this population commonly referred to as classic H. erectus. Given the possible chronological overlaps of classic H. erectus with other archaic Homo, the characterization of this group becomes a key issue when deciphering the taxonomy and evolutionary scenario of the Middle Pleistocene hominins in East Asia. Internally, the most remarkable feature of Zhoukoudian teeth is the highly crenulated enamel-dentine junction (EDJ) and its imprint on the roof of the pulp cavity. So far, this “dendrite-like” EDJ has been found only in East Asia Middle Pleistocene hominins although a large group of samples were assessed, and it could be useful to dentally define classic H. erectus in China. The crenulated EDJ surface, together with the stout roots and the taurodontism could be a mechanism to withstand high biomechanical demand despite a general dentognathic reduction, particularly of the crowns, in these populations.
Recent intensification of winter haze in China linked to foreign emissions and meteorology
Authors: Yang Yang , Wang Hailong , Smith Steven J. , Zhang Rudong , Lou Sijia , Qian Yun , Ma Po-Lun , Rasch Philip J. 
Published: January 2018

AbstractWintertime aerosol pollution in the North China Plain has increased over the past several decades as anthropogenic emissions in China have increased, and has dramatically escalated since the beginning of the 21st century, but the causes and their quantitative attributions remain unclear. Here we use an aerosol source tagging capability implemented in a global aerosol-climate model to assess long-term trends of PM2.5 (particulate matter less than 2.5 μm in diameter) in the North China Plain. Our analysis suggests that the impact of China’s increasing domestic emissions on PM2.5 concentrations over the last two decades of 20th century was partially offset (13%) by decreasing foreign emission over this period. As foreign emissions stabilized after 2000, their counteracting effect almost disappeared, uncovering the impact of China’s increasing domestic emissions that had been partially offset in previous years by reductions in foreign emissions. A slowdown in the impact from foreign emission reductions together with weakening winds explain 25% of the increased PM2.5 trend over 2000–2014 as compared to 1980–2000. Further reductions in foreign emissions are not expected to relieve China’s pollution in the future. Reducing local emissions is the most certain way to improve future air quality in the North China Plain.
SMARCA2-regulated host cell factors are required for MxA restriction of influenza A viruses
Authors: Dornfeld Dominik , Dudek Alexandra H. , Vausselin Thibaut , Günther Sira C. , Hultquist Judd F. , Giese Sebastian , Khokhlova-Cubberley Daria , Chew Yap C. , Pache Lars , Krogan Nevan J. , Garcia-Sastre Adolfo , Schwemmle Martin , Shaw Megan L. 
Published: January 2018

AbstractThe human interferon (IFN)-induced MxA protein is a key antiviral host restriction factor exhibiting broad antiviral activity against many RNA viruses, including highly pathogenic avian influenza A viruses (IAV) of the H5N1 and H7N7 subtype. To date the mechanism for how MxA exerts its antiviral activity is unclear, however, additional cellular factors are believed to be essential for this activity. To identify MxA cofactors we performed a genome-wide siRNA-based screen in human airway epithelial cells (A549) constitutively expressing MxA using an H5N1 reporter virus. These data were complemented with a proteomic screen to identify MxA-interacting proteins. The combined data identified SMARCA2, the ATPase subunit of the BAF chromatin remodeling complex, as a crucial factor required for the antiviral activity of MxA against IAV. Intriguingly, our data demonstrate that although SMARCA2 is essential for expression of some IFN-stimulated genes (ISGs), and the establishment of an antiviral state, it is not required for expression of MxA, suggesting an indirect effect on MxA activity. Transcriptome analysis of SMARCA2-depleted A549-MxA cells identified a small set of SMARCA2-regulated factors required for activity of MxA, in particular IFITM2 and IGFBP3. These findings reveal that several virus-inducible factors work in concert to enable MxA restriction of IAV.
IGFBPL1 Regulates Axon Growth through IGF-1-mediated Signaling Cascades
Authors: Guo Chenying , Cho Kin-Sang , Li Yingqian , Tchedre Kissauo , Antolik Christian , Ma Jie , Chew Justin , Utheim Tor Paaske , Huang Xizhong A. , Yu Honghua , Malik Muhammad Taimur A. , Anzak Nada , Chen Dong Feng 
Published: January 2018

AbstractActivation of axonal growth program is a critical step in successful optic nerve regeneration following injury. Yet the molecular mechanisms that orchestrate this developmental transition are not fully understood. Here we identified a novel regulator, insulin-like growth factor binding protein-like 1 (IGFBPL1), for the growth of retinal ganglion cell (RGC) axons. Expression of IGFBPL1 correlates with RGC axon growth in development, and acute knockdown of IGFBPL1 with shRNA or IGFBPL1 knockout in vivo impaired RGC axon growth. In contrast, administration of IGFBPL1 promoted axon growth. Moreover, IGFBPL1 bound to insulin-like growth factor 1 (IGF-1) and subsequently induced calcium signaling and mammalian target of rapamycin (mTOR) phosphorylation to stimulate axon elongation. Blockage of IGF-1 signaling abolished IGFBPL1-mediated axon growth, and vice versa, IGF-1 required the presence of IGFBPL1 to promote RGC axon growth. These data reveal a novel element in the control of RGC axon growth and suggest an unknown signaling loop in the regulation of the pleiotropic functions of IGF-1. They suggest new therapeutic target for promoting optic nerve and axon regeneration and repair of the central nervous system.
Substitutions of the S4DIV R2 residue (R1451) in NaV1.4 lead to complex forms of paramyotonia congenita and periodic paralyses
Authors: Poulin Hugo , Gosselin-Badaroudine Pascal , Vicart Savine , Habbout Karima , Sternberg Damien , Giuliano Serena , Fontaine Bertrand , Bendahhou Saïd , Nicole Sophie , Chahine Mohamed 
Published: January 2018

AbstractMutations in NaV1.4, the skeletal muscle voltage-gated Na+ channel, underlie several skeletal muscle channelopathies. We report here the functional characterization of two substitutions targeting the R1451 residue and resulting in 3 distinct clinical phenotypes. The R1451L is a novel pathogenic substitution found in two unrelated individuals. The first individual was diagnosed with non-dystrophic myotonia, whereas the second suffered from an unusual phenotype combining hyperkalemic and hypokalemic episodes of periodic paralysis (PP). The R1451C substitution was found in one individual with a single attack of hypoPP induced by glucocorticoids. To elucidate the biophysical mechanism underlying the phenotypes, we used the patch-clamp technique to study tsA201 cells expressing WT or R1451C/L channels. Our results showed that both substitutions shifted the inactivation to hyperpolarized potentials, slowed the kinetics of inactivation, slowed the recovery from slow inactivation and reduced the current density. Cooling further enhanced these abnormalities. Homology modeling revealed a disruption of hydrogen bonds in the voltage sensor domain caused by R1451C/L. We concluded that the altered biophysical properties of R1451C/L well account for the PMC-hyperPP cluster and that additional factors likely play a critical role in the inter-individual differences of clinical expression resulting from R1451C/L.
Expression analysis of candidate genes for fatty acid composition in adipose tissue and identification of regulatory regions
Authors: Revilla Manuel , Puig-Oliveras Anna , Crespo-Piazuelo Daniel , Criado-Mesas Lourdes , Castelló Anna , Fernández Ana I. , Ballester Maria , Folch Josep M. 
Published: January 2018

AbstractThe aim of this work was to study the genetic basis of the backfat expression of lipid-related genes associated with meat quality traits in pigs. We performed a genome-wide association study with the backfat gene expression measured in 44 genes by qPCR and thePorcineSNP60 BeadChipgenotypes in 115 Iberian x Landrace backcross animals. A total of 193 expression-associated SNPs located in 19 chromosomal regions were associated with expression levels ofACSM5,ELOVL6,FABP4,FADS2, andSLC27A4genes. Three expression quantitative trail loci (eQTLs) corresponding toACSM5,FABP4, andFADS2were classified ascis-acting eQTLs, whereas the remaining 16 eQTLs havetrans-regulatory effects. Remarkably, a SNP in theACSM5promoter region and a SNP in the 3′UTR region ofFABP4were the most associated polymorphisms with theACSM5andFABP4expression levels, respectively. Moreover, relevant lipid-related genes mapped in thetrans-eQTLs regions associated with theACSM5,FABP4,FADS2, andSLC27A4genes. Interestingly, atrans-eQTL hotspot on SSC13 regulating the gene expression ofELOVL6,ELOLV5, andSCD, three important genes implicated in the elongation and desaturation of fatty acids, was identified. These findings provide new data to further understand the functional regulatory mechanisms implicated in the variation of fatty acid composition in pigs.
Chaos and dynamical complexity in the quantum to classical transition
Authors: Pokharel Bibek , Misplon Moses Z. R. , Lynn Walter , Duggins Peter , Hallman Kevin , Anderson Dustin , Kapulkin Arie , Pattanayak Arjendu K. 
Published: January 2018

AbstractWe study the largest Lyapunov exponents λ and dynamical complexity for an open quantum driven double-well oscillator, mapping its dependence on coupling to the environment Γ as well as effective Planck’s constant β2. We show that in general λ increases with effective Hilbert space size (as β decreases, or the system becomes larger and closer to the classical limit). However, if the classical limit is regular, there is always a quantum system with λ greater than the classical λ, with several examples where the quantum system is chaotic even though the classical system is regular. While the quantum chaotic attractors are generally of the same family as the classical attractors, we also find quantum attractors with no classical counterpart. Contrary to the standard wisdom, the correspondence limit can thus be the most difficult to achieve for certain classically chaotic systems. These phenomena occur in experimentally accessible regimes.
KIBRA is associated with accelerated cognitive decline and hippocampal atrophy in APOE ε4-positive cognitively normal adults with high Aβ-amyloid burden
Authors: Porter Tenielle , Burnham Samantha C. , Doré Vincent , Savage Greg , Bourgeat Pierrick , Begemann Kimberly , Milicic Lidija , Ames David , Bush Ashley I. , Maruff Paul , Masters Colin L. , Rowe Christopher C. , Rainey-Smith Stephanie , Martins Ralph N. , Groth David , Verdile Giuseppe , Villemagne Victor L. , Laws Simon M. 
Published: January 2018

AbstractA single nucleotide polymorphism, rs17070145, in the KIdney and BRAin expressed protein (KIBRA) gene has been associated with cognition and hippocampal volume in cognitively normal (CN) individuals. However, the impact of rs17070145 on longitudinal cognitive decline and hippocampal atrophy in CN adults at greatest risk of developing Alzheimer’s disease is unknown. We investigated the impact rs17070145 has on the rate of cognitive decline and hippocampal atrophy over six years in 602 CN adults, with known brain Aβ-amyloid levels and whether there is an interactive effect with APOE genotype. We reveal that whilst limited independent effects of KIBRA genotype were observed, there was an interaction with APOE in CN adults who presented with high Aβ-amyloid levels across study duration. In comparison to APOE ε4-ve individuals carrying the rs17070145-T allele, significantly faster rates of cognitive decline (global, p = 0.006; verbal episodic memory, p = 0.004), and hippocampal atrophy (p = 0.04) were observed in individuals who were APOE ε4 + ve and did not carry the rs17070145-T allele. The observation of APOE effects in only non-carriers of the rs17070145-T allele, in the presence of high Aβ-amyloid suggest that carriers of the rs17070145-T allele are conferred a level of resilience to the detrimental effects of high Aβ-amyloid and APOE ε4.
Heterologous pathway assembly reveals molecular steps of fungal terreic acid biosynthesis
Authors: Kong Chuixing , Huang Hezhou , Xue Ying , Liu Yiqi , Peng Qiangqiang , Liu Qi , Xu Qin , Zhu Qiaoyun , Yin Ying , Zhou Xiangshan , Zhang Yuanxing , Cai Menghao 
Published: January 2018

AbstractTerreic acid is a potential anticancer drug as it inhibits Bruton’s tyrosine kinase; however, its biosynthetic molecular steps remain unclear. In this work, the individual reactions of terreic acid biosynthesis were determined by stepwise pathway assembly in a heterologous host, Pichia pastoris, on the basis of previous knockout studies in a native host, Aspergillus terreus. Polyketide synthase AtX was found to catalyze the formation of partially reduced polyketide 6-methylsalicylic acid, followed by 3-methylcatechol synthesis by salicylate 1-monooxygenase AtA-mediated decarboxylative hydroxylation of 6-methylsalicylic acid. Our results show that cytochrome P450 monooxygenase AtE hydroxylates 3-methylcatechol, thus producing the next product, 3-methyl-1,2,4-benzenetriol. A smaller putative cytochrome P450 monooxygenase, AtG, assists with this step. Then, AtD causes epoxidation and hydroxyl oxidation of 3-methyl-1,2,4-benzenetriol and produces a compound terremutin, via which the previously unknown function of AtD was identified as cyclooxygenation. The final step involves an oxidation reaction of a hydroxyl group by a glucose-methanol-choline oxidoreductase, AtC, which leads to the final product: terreic acid. Functions of AtD and AtG were determined for the first time. All the genes were reanalyzed and all intermediates and final products were isolated and identified. Our model fully defines the molecular steps and corrects previous results from the literature.
Dual-functional tunable coding metasurface based on saline water substrate
Authors: Chen Lei , Ma He Liang , Song Xiao Jun , Ruan Ying , Cui Hao Yang 
Published: January 2018

AbstractIn this paper, a dual-functional tunable coding metasurface is presented at X band based on water substrate, which can realize two different functions of specific scattering pattern and absorption at two different frequency ranges. Besides, by changing the salinity of the saline water substrate, the absorption performance in high frequency can be tuned, while the scattering pattern in low frequency remains unchanged. A coding element is designed with small water cavity in it. Three coding sequences with different radiation patterns are designed to verify these functions, and one of them is fabricated and measured. Experimental results have good accordance with our simulations, which demonstrates our schemes. We believe this work can not only broaden our design manner of metasurfaces, but also have plenty potential applications in biological and medical detection domain.
Association of estimated glomerular filtration rate and proteinuria with all-cause mortality in community-based population in China: A Result from Kailuan Study
Authors: Wu Jianwei , Jia Jiaokun , Li Zhaoxia , Pan Hua , Wang Anxin , Guo Xiuhua , Wu Shouling , Zhao Xingquan 
Published: January 2018

AbstractThis study was based on 95391 participants (18–98 years old) from the Kailuan study, which assessed all-cause mortality in a community-based population in northern China according to estimated glomerular filtration rate (eGFR) by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula and proteinuria estimated from urine dipstick results. Data were analysed based on Cox proportional hazards models with adjustment for relevant confounders, and the results were expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). During eight years of follow-up, a total of 6024 participants died. The two indicators, eGFR < 45 ml/min/1.73 m2 and the presence of proteinuria, were independently associated with all-cause mortality. Compared with eGFR ≥45 ml/min/1.73 m2 with negative proteinuria, HRs of all-cause mortality were 1.26 (95% CI 1.10–1.44) for eGFR < 45 ml/min/1.73 m2 without proteinuria, 1.95 (1.78–2.14) for eGFR ≥45 ml/min/1.73 m2 with proteinuria, and 2.63 (2.14–3.23) for eGFR < 45 ml/min/1.73 m2 with proteinuria. The all-cause mortality risk of eGFR and/or proteinuria was much higher in females than in males (P for interaction < 0.01). In conclusion, both severely decreased eGFR and proteinuria are independent predictors of all-cause mortality in the general northern Chinese population. A combination of severely decreased eGFR and proteinuria increases the risk of all-cause mortality, which is even over 5-fold higher in females.
Therapeutic effects of anti-CD154 antibody in cynomolgus monkeys with advanced rheumatoid arthritis
Authors: Choi Eun Wha , Lee Kyo Won , Park Hyojun , Kim Hwajung , Lee Jong Hyun , Song Ji Woo , Yang Jehoon , Kwon Yeongbeen , Kim Tae Min , Park Jae Berm , Kim Sungjoo 
Published: January 2018

AbstractRheumatoid arthritis is one major chronic inflammatory systemic autoimmune disease. The CD154-CD40 interactions play a critical role in the regulation of immune responses and the maintenance of autoimmunity. Therefore, we aimed to determine whether anti-CD154 antibody treatment show positive effects on immunomodulation and clinical improvement of sustained severe rheumatoid arthritis in cynomolgus monkeys. Arthritis was induced using chicken type II collagen (CII) and arthritic monkey were divided into control and anti-CD154 treatment groups based on their concentrations of anti-CII antibodies on week 7 post-immunization. Blood and tissue samples were collected on week 16 post-immunization. Anti-CD154 antibody treatment improved arthritis and movement, and significantly decreased the numbers of proliferating B cells and the serum levels of anti-type II collagen antibody and sCD154 compared with non-treatment group. Further anti-CD154 antibody treatment significantly decreased the percentage of CD4+ cells and the ratio of CD4+ to CD8+ T cells and significantly increased the percentage of CD8+ cells and effector memory CD8+ cells in peripheral blood. We have shown for the first time in a nonhuman primate model of RA that CD154 blockade has beneficial effects. This study might be valuable as preclinical data of CD154 blockade in nonhuman primate models of severe rheumatoid arthritis.
A Wearable High-Resolution Facial Electromyography for Long Term Recordings in Freely Behaving Humans
Authors: Inzelberg Lilah , Rand David , Steinberg Stanislav , David-Pur Moshe , Hanein Yael 
Published: January 2018

AbstractHuman facial expressions are a complex capacity, carrying important psychological and neurological information. Facial expressions typically involve the co-activation of several muscles; they vary between individuals, between voluntary versus spontaneous expressions, and depend strongly on personal interpretation. Accordingly, while high-resolution recording of muscle activation in a non-laboratory setting offers exciting opportunities, it remains a major challenge. This paper describes a wearable and non-invasive method for objective mapping of facial muscle activation and demonstrates its application in a natural setting. We focus on muscle activation associated with “enjoyment”, “social” and “masked” smiles; three categories with distinct social meanings. We use an innovative, dry, soft electrode array designed specifically for facial surface electromyography recording, a customized independent component analysis algorithm, and a short training procedure to achieve the desired mapping. First, identification of the orbicularis oculi and the levator labii superioris was demonstrated from voluntary expressions. Second, the zygomaticus major was identified from voluntary and spontaneous Duchenne and non-Duchenne smiles. Finally, using a wireless device in an unmodified work environment revealed expressions of diverse emotions in face-to-face interaction. Our high-resolution and crosstalk-free mapping, along with excellent user-convenience, opens new opportunities in gaming, virtual-reality, bio-feedback and objective psychological and neurological assessment.
Kisspeptin-10 (KP-10) stimulates osteoblast differentiation through GPR54-mediated regulation of BMP2 expression and activation
Authors: Son Hyo-Eun , Kim Kyeong-Min , Kim Eun-Jung , Jang Won-Gu 
Published: January 2018

AbstractKisspeptin-10 (KP-10) acts as a tumor metastasis suppressor via its receptor, G-protein-coupled receptor 54 (GPR54). The KP-10-GPR54 system plays an important role in embryonic kidney development. However, its function in osteoblast differentiation is unknown. Osteoblast differentiation is controlled by a range of hormones and cytokines, such as bone morphogenetic protein (BMPs), and multiple transcription factors, such as Runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), and Distal-less homeobox 5 (Dlx5). In the present study, KP-10-treatment significantly increased the expression of osteogenic genes, including mRNA and protein levels of BMP2, in C3H10T1/2 cells. Moreover, KP-10 induced BMP2-luc activity and increased phosphorylation of Smad1/5/9. In addition, NFATc4 specifically mediated KP-10-induced BMP2 gene expression. However, KP-10 treatment did not induce expression of the BMP2 and Runx2 genes in GPR54−/− cells. To examine whether KP-10 induced secretion of BMP2 to the culture medium, we used the conditioned-medium (C.M) of KP-10 treated medium on C3H10T1/2 cells. Dlx5 and Runx2 expressions were higher in GPR54−/− cells treated with C.M than in those treated with KP-10. These results demonstrate that BMP2 protein has an autocrine effect upon KP-10 treatment. Taken together, these findings suggest that KP-10/GPR54 signaling induces osteoblast differentiation via NFATc4-mediated BMP2 expression.