bluuebunny/crossref_metadata_2025_split huggingface dataset:
Corylin increases the sensitivity of hepatocellular carcinoma cells to chemotherapy through long noncoding RNA RAD51-AS1-mediated inhibition of DNA repair
Authors: Chen Chin-Chuan , Chen Chi-Yuan , Ueng Shir-Hwa , Hsueh Chuen , Yeh Chau-Ting , Ho Jar-Yi , Chou Li-Fang , Wang Tong-Hong 
Published: May 2018

AbstractCorylin, a biologically active agent extracted from Psoralea corylifolia L. (Fabaceae), promotes bone differentiation and inhibits inflammation. Currently, few reports have addressed the biological functions that are regulated by corylin, and to date, no studies have investigated its antitumor activity. In this study, we used cell functional assays to analyze the antitumor activity of corylin in hepatocellular carcinoma (HCC). Furthermore, whole-transcriptome assays were performed to identify the downstream genes that were regulated by corylin, and gain-of-function and loss-of-function experiments were conducted to examine the regulatory roles of the above genes. We found that corylin significantly inhibited the proliferation, migration, and invasion of HCC cells and increased the toxic effects of chemotherapeutic agents against HCC cells. These properties were due to the induction of a long noncoding RNA, RAD51-AS1, which bound to RAD51 mRNA, thereby inhibiting RAD51 protein expression, thus inhibiting the DNA damage repair ability of HCC cells. Animal experiments also showed that a combination treatment with corylin significantly increased the inhibitory effects of the chemotherapeutic agent etoposide (VP16) on tumor growth. These findings indicate that corylin has strong potential as an adjuvant drug in HCC treatment and that corylin can strengthen the therapeutic efficacy of chemotherapy and radiotherapy.
microRNA-501-3p suppresses metastasis and progression of hepatocellular carcinoma through targeting LIN7A
Authors: Luo Chubin , Yin Dan , Zhan Hao , Borjigin Uyunbilig , Li Chuanjiang , Zhou Zhengjun , Hu Zhiqiang , Wang Pengcheng , Sun Qiman , Fan Jia , Zhou Jian , Wang Xin , Zhou Shaolai , Huang Xiaowu 
Published: May 2018

AbstractIncreasing numbers of evidences have demonstrated that microRNAs (miRNAs) are implicated in metastasis and progression of hepatocellular carcinoma (HCC). However, their detailed expression levels and actual functions in HCCs have not been fully clarified yet. Results from our recent study revealed that some miRNAs were particularly related to metastasis of HCCs. As one of these newly found miRNAs, miR-501-3p showed to highly involve into metastatic process of HCCs. Here we reported that the expression of miR-501-3p was decreased in both metastatic HCC cell lines and tissue samples from HCC patients with recurrence and metastasis. Downregulation of miR-501-3p correlated with tumor progression and poor prognosis in the HCC patients. Results of functional analyses revealed that overexpression of miR-501-3p in HCCLM3 cancer cells inhibited their proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT), while miR-501-3p loss in PLC/PRF/5 cancer cells facilitated all these cellular activities. In addition, Lin-7 homolog A (LIN7A) was directly targeted by miR-501-3p to mediate the suppression effects on metastasis in HCC cells. miR-501-3p suppresses metastasis and progression of HCCs through targeting LIN7A. This finding suggests that miR-501-3p could be used as a potential prognostic predictor as well as a potential therapeutic tool for HCC therapies.
P2RX7-MAPK1/2-SP1 axis inhibits MTOR independent HSPB1-mediated astroglial autophagy
Authors: Kim Ji-Eun , Ko Ah-Reum , Hyun Hye-Won , Min Su-Ji , Kang Tae-Cheon 
Published: May 2018

AbstractRecently, we have reported that heat shock protein B1 (HSPB1) and purinergic receptor P2X7 (P2RX7) are involved in astroglial autophagy (clasmatodendrosis), following status epilepticus (SE). However, the underlying mechanisms of astroglial autophagy have not been completely established. In the present study, we found that the lacking ofP2rx7led to prolonged astroglial HSPB1 induction due to impaired mitogen-activated protein kinase 1/2 (MAPK1/2)-mediated specificity protein 1 (SP1) phosphorylation, following kainic acid-induced SE. Subsequently, the upregulated HSPB1 itself evoked ER stress and exerted protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1, AMPK1)/unc-51 such as autophagy activating kinase 1 (ULK1)- and AKT serine/threonine kinase 1 (AKT1)/glycogen synthase kinase 3 beta (GSK3B)/SH3-domain GRB2-like B1 (SH3GLB1)-mediated autophagic pathways, independent of mechanistic target of rapamycin (MTOR) activity in astrocytes. These findings provide a novel purinergic suppression mechanism to link chaperone expression to autophagy in astrocytes. Therefore, we suggest that P2RX7 may play an important role in the regulation of autophagy by the fine-tuning of HSPB1 expression.
MicroRNA-29b/142-5p contribute to the pathogenesis of biliary atresia by regulating the IFN-γ gene
Authors: Yang Yifan , Jin Zhu , Dong Rui , Zheng Chao , Huang Yanlei , Zheng Yijie , Shen Zhen , Chen Gong , Luo Xiaoying , Zheng Shan 
Published: May 2018

AbstractBiliary atresia is one of the most common liver disease in infancy. The cause and pathogenesis remain largely unknown. This study aimed to investigate the potential regulatory effect of miR-29b/142-5p on IFN-γ gene methylation. miRNAs microarray was performed on four pairs of liver and blood specimens from biliary atresia and choledochal cysts. We found the overexpression of miR-142-5p and mRNA level of DNA methyltransferase (DNMT) 1, and miR-29b and DNMT3a/DNMT3b were significantly negatively correlated in biliary atresia livers. Meanwhile, the methylation of the LINE-1, ALU and SAT2 repetitive sequences and the IFN-γ promoter was lower, but the expression of IFN-γ was upregulated. After transfected with DNMTs siRNAs, downregulation of DNMTs exerted a significant hypomethylating effect on the repetitive sequences, which led to upregulation of IFN-γ in Jurkat cells. The direct interactions between miR-29b and DNMT3a/3b, and miR-142-5p and DNMT1 were identified using luciferase reporter assays. By transfecting mimics of miR-29b/142-5p into Jurkat cells, we found overexpression of miR-29b/142-5p markedly suppressed expression of DNMTs. Furthermore, the methylation of repetitive sequences and the IFN-γ promoter region were remarkably downregulated, and with elevated IFN-γ expression. After transfecting the miRNA inhibitors, the levels of DNMTs and the methylation of the IFN-γ gene promoter region was upregulated, while levels of IFN-γ were markedly suppressed. Our study suggested that miRNA-29b/142-5p overexpression and targeted inhibition of DNMTs expression resulted in decreased overall gene methylation and overexpression of the methylation-sensitive IFN-γ gene.
Gene-by-environment interactions that disrupt mitochondrial homeostasis cause neurodegeneration in C. elegans Parkinson’s models
Authors: Kim Hanna , Perentis Rylee J. , Caldwell Guy A. , Caldwell Kim A. 
Published: May 2018

AbstractParkinson’s disease (PD) is a complex multifactorial disorder where environmental factors interact with genetic susceptibility. Accumulating evidence suggests that mitochondria have a central role in the progression of neurodegeneration in sporadic and/or genetic forms of PD. We previously reported that exposure to a secondary metabolite from the soil bacterium, Streptomyces venezuelae, results in age- and dose-dependent dopaminergic (DA) neurodegeneration in Caenorhabditis elegans and human SH-SY5Y neurons. Initial characterization of this environmental factor indicated that neurodegeneration occurs through a combination of oxidative stress, mitochondrial complex I impairment, and proteostatic disruption. Here we present extended evidence to elucidate the interaction between this bacterial metabolite and mitochondrial dysfunction in the development of DA neurodegeneration. We demonstrate that it causes a time-dependent increase in mitochondrial fragmentation through concomitant changes in the gene expression of mitochondrial fission and fusion components. In particular, the outer mitochondrial membrane fission and fusion genes, drp-1 (a dynamin-related GTPase) and fzo-1 (a mitofusin homolog), are up- and down-regulated, respectively. Additionally, eat-3, an inner mitochondrial membrane fusion component, an OPA1 homolog, is also down regulated. These changes are associated with a metabolite-induced decline in mitochondrial membrane potential and enhanced DA neurodegeneration that is dependent on PINK-1 function. Genetic analysis also indicates an association between the cell death pathway and drp-1 following S. ven exposure. Metabolite-induced neurotoxicity can be suppressed by DA-neuron-specific RNAi knockdown of eat-3. AMPK activation by 5-amino-4-imidazole carboxamide riboside (AICAR) ameliorated metabolite- or PINK-1-induced neurotoxicity; however, it enhanced neurotoxicity under normal conditions. These studies underscore the critical role of mitochondrial dynamics in DA neurodegeneration. Moreover, given the largely undefined environmental components of PD etiology, these results highlight a response to an environmental factor that defines distinct mechanisms underlying a potential contributor to the progressive DA neurodegeneration observed in PD.
The long noncoding RNA GAS5 negatively regulates the adipogenic differentiation of MSCs by modulating the miR-18a/CTGF axis as a ceRNA
Authors: Li Ming , Xie Zhongyu , Wang Peng , Li Jinteng , Liu Wenjie , Tang Su’an , Liu Zhenhua , Wu Xiaohua , Wu Yanfeng , Shen Huiyong 
Published: May 2018

AbstractMesenchymal stem cells (MSCs) are important pluripotent stem cells and a major source of adipocytes in the body. However, the mechanism of adipogenic differentiation has not yet been completely elucidated. In this study, the long noncoding RNA GAS5 was found to be negatively correlated with MSC adipogenic differentiation. GAS5 overexpression negatively regulated adipocyte formation, whereas GAS5 knockdown had the opposite effect. Further mechanistic analyses using luciferase reporter assays revealed that GAS5 regulates the adipogenic differentiation of MSCs by acting as competing endogenous RNA (ceRNA) to sponge miR-18a, which promotes adipogenic differentiation. Mutation of the binding sites for GAS5 in miR-18a abolished the effect of the interaction. The miR-18a mimic and inhibitor reversed the negative regulatory effect of GAS5 on MSCs adipogenic differentiation. In addition, GAS5 inhibited miR-18a, which downregulates connective tissue growth factor (CTGF) expression, to negatively regulate the adipogenic differentiation of MSCs. Taken together, the results show that GAS5 serves as a sponge for miR-18a, inhibiting its capability to suppress CTGF protein translation and ultimately decreasing the adipogenic differentiation of MSCs. GAS5 is an important molecule involved in the adipogenic differentiation of MSCs and may contribute to the functional regulation and clinical applications of MSCs.
L-SCRaMbLE as a tool for light-controlled Cre-mediated recombination in yeast
Authors: Hochrein Lena , Mitchell Leslie A. , Schulz Karina , Messerschmidt Katrin , Mueller-Roeber Bernd 
Published: May 2018

AbstractThe synthetic yeast genome constructed by the International Synthetic Yeast Sc2.0 consortium adds thousands of loxPsym recombination sites to all 16 redesigned chromosomes, allowing the shuffling of Sc2.0 chromosome parts by the Cre-loxP recombination system thereby enabling genome evolution experiments. Here, we present L-SCRaMbLE, a light-controlled Cre recombinase for use in the yeast Saccharomyces cerevisiae. L-SCRaMbLE allows tight regulation of recombinase activity with up to 179-fold induction upon exposure to red light. The extent of recombination depends on induction time and concentration of the chromophore phycocyanobilin (PCB), which can be easily adjusted. The tool presented here provides improved recombination control over the previously reported estradiol-dependent SCRaMbLE induction system, mediating a larger variety of possible recombination events in SCRaMbLE-ing a reporter plasmid. Thereby, L-SCRaMbLE boosts the potential for further customization and provides a facile application for use in the S. cerevisiae genome re-engineering project Sc2.0 or in other recombination-based systems.
Emotional reactivity and perspective-taking in individuals with and without severe depressive symptoms
Authors: Imbault Constance , Kuperman Victor 
Published: May 2018

AbstractThe perspective-taking ability to imagine another person’s feelings and thoughts is paramount for successful communication. This study pursued two questions regarding the link between perspective-taking and depressive symptomatology in a task where participants provided responses to words ranging in their positivity. First, we examined in a between-participants experimental manipulation how the presence of depressive symptoms influenced participants’ emotional reactivity. Second, we measured within-participants, how their responses change as a function of the perspective they are assigned to take, that of a depressed or a non-depressed person. Our main interest is in the interaction of the two effects: we examine how one’s emotional state determines the ability to engender someone else’s responses. Our central finding is that depressive symptoms lead to emotional insensitivity, i.e., weaker responses to extremely positive and negative words. Furthermore, depressive symptoms come with a much weaker ability to take a non-depressed perspective. Finally, non-depressed participants demonstrated an excellent ability to mimic the blunt affect of depression when responding for the other group, suggesting that the outlook of a depressed individual is available to people throughout the range of depressive symptomatology. We discuss the implications of these findings for quantifying emotional reactivity during depression, as well as the diagnosis and prognosis of depression.
Increase In Il-31 Serum Levels Is Associated With Reduced Structural Damage In Early Axial Spondyloarthritis
Authors: Rosine Nicolas , Etcheto Adrien , Hendel-Chavez Houria , Seror Raphaèle , Briot Karine , Molto Anna , Chanson Philippe , Taoufik Yassine , Wendling Daniel , Lories Rik , Berenbaum Francis , van den Berg Rosaline , Claudepierre Pascal , Feydy Antoine , Dougados Maxime , Roux Christian , Miceli-Richard Corinne 
Published: May 2018

AbstractIn spondyloarthritis, little is known about the relation between circulating cytokines and patient phenotype. We have quantified serum levels of T helper type 1 cell (Th1), Th2 and Th17 cytokines in patients with recent-onset axial spondyloarthritis (AxSpA) from the DESIR cohort, a prospective, multicenter French cohort consisting of 708 patients with recent-onset inflammatory back pain (duration >3 months but <3 years) suggestive of AxSpA. Serum levels of Th1, Th2, and Th17 cytokines were assessed at baseline in patients from the DESIR cohort fulfilling the ASAS criteria (ASAS+) and were compared with age- and sex-matched healthy controls. At baseline, ASAS+ patients (n = 443) and healthy controls (n = 79) did not differ in levels of most of the Th1, Th2 and Th17 cytokines except for IL-31, and sCD40L, which were significantly higher for ASAS+ patients than controls (p < 0.001 and p = 0.012, respectively). On multivariable analysis of ASAS+ patients, IL-31 level was associated with sCD40L level (p < 0.0001), modified Stoke AS Spine Score (mSASSS) < 1 (p = 0.035). The multivariable analyses showed that IL-31 was an independent factor associated with mSASSS < 1 (p = 0.001) and low bone mineral density (p = 0.01). Increased level of IL-31 might protect against structural damage but is also related to low BMD.
Hcp/fcc nucleation in bcc iron under different anisotropic compressions at high strain rate: Molecular dynamics study
Authors: Shao Jian-Li , Wang Pei , Zhang Feng-Guo , He An-Min 
Published: May 2018

AbstractPrevious researches have revealed the importance of shear and the orientation dependence in the structural transition of iron. In this work, we introduce a series of shear deformations by adjusting the strain ratio between the longitudinal ([001]) and transversal ([010] and [100]) directions, and then investigate this structural transition under different anisotropic compressions with molecular dynamics simulations. It is found that the shear deformation can lower the transition pressure notably, and even change the nucleation structure and morphology. Under 1D-dominated compression (along (001) direction), there only appears hcp nucleation with a few fcc stacking faults. For other cases, more equivalent planes will be activated and fcc structure begins to nucleate. Under 2D-dominated compression (along (010) and (001) directions), the fcc mass fraction is already over the hcp phase. At last, we compare the variations of shear stress and potential energy for different phases, and present the sliding mechanism under typical anisotropic compressions.
Detection of chikungunya virus DNA using two-dimensional MoS2 nanosheets based disposable biosensor
Authors: Singhal Chaitali , Khanuja Manika , Chaudhary Nahid , Pundir C. S. , Narang Jagriti 
Published: May 2018

AbstractDevelopment of platforms for a reliable, rapid, sensitive and selective detection of chikungunya virus (CHIGV) is the need of the hour in developing countries. To the best of our knowledge, there are no reports available for the electrochemical detection of CHIGVDNA. Therefore, we aim at developing a biosensor based on molybdenum disulphide nanosheets (MoS2NSs) for the point-of-care diagnosis of CHIGV. Briefly, MoS2NSs were synthesized by chemical route and characterized using scanning electron microscopy, transmission electron microscopy, UV-Vis spectroscopy, Raman spectroscopy and X-Ray Diffraction. MoS2NSs were then subjected to physical adsorption onto the screen printed gold electrodes (SPGEs) and then employed for the detection of CHIGV DNA using electrochemical voltammetric techniques. Herein, the role of MoS2NSs is to provide biocompatibility to the biological recognition element on the surface of the screen printed electrodes. The detection strategy employed herein is the ability of methylene blue to interact differentially with the guanine bases of the single and double-stranded DNA which leads to change in the magnitude of the voltammetric signal. The proposed genosensor exhibited a wide linear range of 0.1 nM to 100 µM towards the chikungunya virus DNA.
The opto-locomotor reflex as a tool to measure sensitivity to moving random dot patterns in mice
Authors: Kirkels L. A. M. H. , Zhang W. , Havenith M. N. , Tiesinga P. , Glennon J. , van Wezel R. J. A. , Duijnhouwer J. 
Published: May 2018

AbstractWe designed a method to quantify mice visual function by measuring reflexive opto-locomotor responses. Mice were placed on a Styrofoam ball at the center of a large dome on the inside of which we projected moving random dot patterns. Because we fixed the heads of the mice in space and the ball was floating on pressurized air, locomotion of the mice was translated to rotation of the ball, which we registered. Sudden onsets of rightward or leftward moving patterns caused the mice to reflexively change their running direction. We quantified the opto-locomotor responses to different pattern speeds, luminance contrasts, and dot sizes. We show that the method is fast and reliable and the magnitude of the reflex is stable within sessions. We conclude that this opto-locomotor reflex method is suitable to quantify visual function in mice.
NDE1 positively regulates oligodendrocyte morphological differentiation
Authors: Shimizu Shoko , Ishino Yugo , Tohyama Masaya , Miyata Shingo 
Published: May 2018

AbstractOligodendrocytes, the myelin-forming cells in the central nervous system (CNS), undergo morphological differentiation characterized by elaborated branched processes to enwrap neuronal axons. However, the basic molecular mechanisms underlying oligodendrocyte morphogenesis remain unknown. Herein, we describe the essential roles of Nuclear Distribution E Homolog 1 (NDE1), a dynein cofactor, in oligodendrocyte morphological differentiation. In the mouse corpus callosum, Nde1 mRNA expression was detected in oligodendrocyte lineage cells at the postnatal stage. In vitro analysis revealed that downregulation of NDE1 by siRNA impaired the outgrowth and extensive branching of oligodendrocyte processes and led to a decrease in the expression of myelin-related markers, namely, CNPase and MBP. In myelinating co-cultures with dorsal root ganglion (DRG) neurons, NDE1-knockdown oligodendrocyte precursor cells (OPCs) failed to develop into MBP-positive oligodendrocytes with multiple processes contacting DRG axons. Immunoprecipitation studies showed that NDE1 interacts with the dynein intermediate chain (DIC) in oligodendrocytes, and an overexpressed DIC-binding region of NDE1 exerted effects on oligodendrocyte morphogenesis that were similar to those following NDE1 knockdown. Furthermore, NDE1-knockdown-impaired oligodendrocyte process formation was rescued by siRNA-resistant wild-type NDE1 but not by DIC-binding region-deficient NDE1 overexpression. These results suggest that NDE1 plays a crucial role in oligodendrocyte morphological differentiation via interaction with dynein.
Honey bees consider larval nutritional status rather than genetic relatedness when selecting larvae for emergency queen rearing
Authors: Sagili Ramesh R. , Metz Bradley N. , Lucas Hannah M. , Chakrabarti Priyadarshini , Breece Carolyn R. 
Published: May 2018

AbstractIn honey bees and many other social insects, production of queens is a vital task, as colony fitness is dependent on queens. The factors considered by honey bee workers in selecting larvae to rear new queens during emergency queen rearing are poorly understood. Identifying these parameters is critical, both in an evolutionary and apicultural context. As female caste development in honey bees is dependent on larval diet (i.e. nutrition), we hypothesized that larval nutritional state is meticulously assessed and used by workers in selection of larvae for queen rearing. To test this hypothesis, we conducted a series of experiments manipulating the nutritional status of one day old larvae by depriving them of brood food for a four-hour period, and then allowing workers to choose larvae for rearing queens from nutritionally deprived and non-deprived larvae. We simultaneously investigated the role of genetic relatedness in selection of larvae for queen rearing. In all the experiments, significantly greater numbers of non-deprived larvae than deprived larvae were selected for queen rearing irrespective of genetic relatedness. Our results demonstrate that honey bees perceive the nutritional state of larvae and use that information when selecting larvae for rearing queens in the natural emergency queen replacement process.