Epstein-barr virus-encoded latent membrane protein 1 impairs G2 checkpoint in human nasopharyngeal epithelial cells through defective Chk1 activation

Nasopharyngeal carcinoma (NPC) is a common cancer in Southeast Asia, particularly in southern regions of China. EBV infection is closely associated with NPC and has long been postulated to play an etiological role in the development of NPC. However, the role of EBV in malignant transformation of nasopharyngeal epithelial cells remains enigmatic. The current hypothesis of NPC development is that premalignant nasopharyngeal epithelial cells harboring genetic alterations support EBV infection and expression of EBV genes induces further genomic instability to facilitate the development of NPC. The latent membrane protein 1 (LMP1) is a well-documented EBV-encoded oncogene. The involvement of LMP1 in human epithelial malignancies has been implicated, but the mechanisms of oncogenic actions of LMP1, particularly in nasopharyngeal cells, are unclear. Here we observed that LMP1 expression in nasopharyngeal epithelial cells impaired G2 checkpoint, leading to formation of unrepaired chromatid breaks in metaphases after γ-ray irradiation. We further found that defective Chk1 activation was involved in the induction of G2 checkpoint defect in LMP1-expressing nasopharyngeal epithelial cells. Impairment of G2 checkpoint could result in loss of the acentrically broken chromatids and propagation of broken centric chromatids in daughter cells exiting mitosis, which facilitates chromosome instability. Our findings suggest that LMP1 expression facilitates genomic instability in cells under genotoxic stress. Elucidation of the mechanisms involved in LMP1-induced genomic instability in nasopharyngeal epithelial cells will shed lights on the understanding of role of EBV infection in NPC development. © 2012 Deng et al.published_or_final_versio

Effect of a qigong intervention program on telomerase activity and psychological stress in abused Chinese women: a randomized, wait-list controlled trial

BACKGROUND: Abused women, who suffer from chronic psychological stress, have been shown to have shorter telomeres than never abused women. Telomere shortening is associated with increased risk of cell death, and it is believed that adopting health-promoting behaviors can help to increase the activity of telomerase, an enzyme that counters telomere shortening. Qigong is an ancient Chinese mind-body integration, health-oriented practice designed to enhance the function of qi, an energy that sustains well-being. Therefore, an assessor-blind, randomized, wait-list controlled trial was developed to evaluate the effect of a qigong intervention on telomerase activity (primary objective) and proinflammatory cytokines, perceived stress, perceived coping, and depressive symptoms (secondary objectives) in abused Chinese women. METHODS/DESIGN: A total of 240 Chinese women, aged >/= 18 years, who have been abused by an intimate partner within the past three years will be recruited from a community setting in Hong Kong and randomized to receive either a qigong intervention or wait-list control condition as follows: the qigong intervention will comprise (i) a 2-hour group qigong training session twice a week for 6 weeks, (ii) a 1-hour follow-up group qigong exercise session once a week for 4 months, and (iii) a 30-minute self-practice qigong exercise session once a day for 5.5 months. The wait-list control group will receive qigong training after the intervention group completes the program. Upon completion of the qigong intervention program, it is expected that abused Chinese women in the intervention group will have higher levels of telomerase activity and perceived coping and lower levels of proinflammatory cytokines, perceived stress, and depressive symptoms than will abused Chinese women in the wait-list control group. DISCUSSION: This study will provide information about the effect of qigong exercise on telomerase activity and chronic psychological stress in abused Chinese women. The findings will inform the design of interventions to relieve the effects of IPV-related psychological stress on health. Also, the concept that health-promoting behaviors could slow down cellular aging might even motivate abused women to change their lifestyles. TRIAL REGISTRATION: Current Controlled Trials NCT02060123. Registered February 6, 2014.published_or_final_versio

Efficient immortalization of primary nasopharyngeal epithelial cells for EBV infection study.

Nasopharyngeal carcinoma (NPC) is common among southern Chinese including the ethnic Cantonese population living in Hong Kong. Epstein-Barr virus (EBV) infection is detected in all undifferentiated type of NPC in this endemic region. Establishment of stable and latent EBV infection in premalignant nasopharyngeal epithelial cells is an early event in NPC development and may contribute to its pathogenesis. Immortalized primary nasopharyngeal epithelial cells represent an important tool for investigation of EBV infection and its tumorigenic potential in this special type of epithelial cells. However, the limited availability and small sizes of nasopharyngeal biopsies have seriously restricted the establishment of primary nasopharyngeal epithelial cells for immortalization. A reliable and effective method to immortalize primary nasopharyngeal epithelial cells will provide unrestricted materials for EBV infection studies. An earlier study has reported that Bmi-1 expression could immortalize primary nasopharyngeal epithelial cells. However, its efficiency and actions in immortalization have not been fully characterized. Our studies showed that Bmi-1 expression alone has limited ability to immortalize primary nasopharyngeal epithelial cells and additional events are often required for its immortalization action. We have identified some of the key events associated with the immortalization of primary nasopharyngeal epithelial cells. Efficient immortalization of nasopharyngeal epithelial cells could be reproducibly and efficiently achieved by the combined actions of Bmi-1 expression, activation of telomerase and silencing of p16 gene. Activation of MAPK signaling and gene expression downstream of Bmi-1 were detected in the immortalized nasopharyngeal epithelial cells and may play a role in immortalization. Furthermore, these newly immortalized nasopharyngeal epithelial cells are susceptible to EBV infection and supported a type II latent EBV infection program characteristic of EBV-infected nasopharyngeal carcinoma. The establishment of an efficient method to immortalize primary nasopharyngeal epithelial cells will facilitate the investigation into the role of EBV infection in pathogenesis of nasopharyngeal carcinoma.published_or_final_versio

Measuring non-polyaminated lipocalin-2 for cardiometabolic risk assessment

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Direct Detection of Pure ac Spin Current by X-Ray Pump-Probe Measurements.

PublishedThis is the author accepted manuscript. The final version is available from American Physical Society via the DOI in this record.There is another ORE record for this article: http://hdl.handle.net/10871/22513Despite recent progress in spin-current research, the detection of spin current has mostly remained indirect. By synchronizing a microwave waveform with synchrotron x-ray pulses, we use the ferromagnetic resonance of the Py (Ni_{81}Fe_{19}) layer in a Py/Cu/Cu_{75}Mn_{25}/Cu/Co multilayer to pump a pure ac spin current into the Cu_{75}Mn_{25} and Co layers, and then directly probe the spin current within the Cu_{75}Mn_{25} layer and the spin dynamics of the Co layer by x-ray magnetic circular dichroism. This element-resolved pump-probe measurement unambiguously identifies the ac spin current in the Cu_{75}Mn_{25} layer.We acknowledge helpful discussion with Arne Brataas. Financial support from the National Science Foundation Grant No. DMR-1504568, Future Materials Discovery Program through the National Research Foundation of Korea (Grant No. 2015M3D1A1070467), and Science Research Center Program through the National Research Foundation of Korea (Grant No. 2015R1A5A1009962) is gratefully acknowledged. The Advanced Light Source is supported by the U.S. Department of Energy under Award No. DE-AC02-05CH11231. J. D. acknowledges fellowship support from the China Scholarship Council and National Science Foundation of China under Grant No. 51331006. L. R. S., P. S. K., and R. J. H. acknowledge the support of the Engineering and Physical Sciences Research Council (EPSRC) through Grants No. EP/J018767/1 and No. EP/ I038470/1. G. v. d. L. acknowledges support of the EPSRC through Grant No. EP/J018767/1

Emotional Sentence Annotation Helps Predict Fiction Genre

Fiction, a prime form of entertainment, has evolved into multiple genres which one can broadly attribute to different forms of stories. In this paper, we examine the hypothesis that works of fiction can be characterised by the emotions they portray. To investigate this hypothesis, we use the work of fictions in the Project Gutenberg and we attribute basic emotional content to each individual sentence using Ekman’s model. A time-smoothed version of the emotional content for each basic emotion is used to train extremely randomized trees. We show through 10-fold Cross-Validation that the emotional content of each work of fiction can help identify each genre with significantly higher probability than random. We also show that the most important differentiator between genre novels is fear

Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C. parvum (106 oocysts) provides robust protective immunity against re-challenge despite ongoing PM. C. parvum priming restores mucosal Th1-type effectors (CD3+CD8+CD103+ T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with Cryptosporidium antigens expressed in the S. Typhi vector 908htr, however, do not enhance Th1-type responses to C. parvum challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated S. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate C. parvum severity during PM, but neither as effectively as viable C. parvum priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to C. parvum, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically C. parvum priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of Cryptosporidium immunity and future vaccine strategies in malnourished children

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Fish passage design for sustainable hydropower in the temperate Southern Hemisphere:An evidence review

The development of hydropower and other infrastructure that disrupts river connectivity poses a serious threat to highly endemic and genetically distinct freshwater fish species in temperate parts of the Southern Hemisphere. Such locations have been neglected in previous reviews on fish passage. Fishways have long been constructed to mitigate the impacts of riverine barriers on fish, yet they have often failed for all but the largest, strongest swimming taxa. This is a particular problem in the temperate south, where the majority of species arewhich is home to native species that are non-recreational and generally small-bodied with weak swimming abilities (e.g. Galaxiidae) relative to typical target species for fishway design (e.g. Salmonidae). Using the Eco Evidence method for rapid evidence synthesis, we undertook an assessment of evidence for effective fishway design focusing on species representative of the temperate south, including eel and lamprey. Systematic literature searches resulted in 630 publications. Through a rigorous screening process these were reduced to 46 publications containing 76 evidence items across 19 hypotheses relating to design criteria for upstream and downstream passage. We found an overwhelming lack of evidence for effective fishway design in the temperate south. Particular deficiencies were found with regard to the design of effective facilities for downstream passage. The attraction and entrance of upstream migrating fish into fishways is also relatively under-researched. Given the urgent need for effective fishways in the temperate south, these results justify an approach to fishway design based on a combination of empirical data and expert knowledge. In the meantime, significant resources should be assigned to improve the evidence base through high quality research. The particular deficiencies identified here could guide that research agenda

Effects of pretreatments of Napier Grass with deionized water, sulfuric acid and sodium hydroxide on pyrolysis oil characteristics

The depletion of fossil fuel reserves has led to increasing interest in liquid bio-fuel from renewable biomass. Biomass is a complex organic material consisting of different degrees of cellulose, hemicellulose, lignin, extractives and minerals. Some of the mineral elements tend to retard conversions, yield and selectivity during pyrolysis processing. This study is focused on the extraction of mineral retardants from Napier grass using deionized water, dilute sodium hydroxide and sulfuric acid and subsequent pyrolysis in a fixed bed reactor. The raw biomass was characterized before and after each pretreatment following standard procedure. Pyrolysis study was conducted in a fixed bed reactor at 600 o�C, 30 �C/min and 30 mL/min N2 flow. Pyrolysis oil (bio-oil) collected was analyzed using standard analytic techniques. The bio-oil yield and characteristics from each pretreated sample were compared with oil from the non-pretreated sample. Bio-oil yield from the raw sample was 32.06 wt% compared to 38.71, 33.28 and 29.27 wt% oil yield recorded from the sample pretreated with sulfuric acid, deionized water and sodium hydroxide respectively. GC–MS analysis of the oil samples revealed that the oil from all the pretreated biomass had more value added chemicals and less ketones and aldehydes. Pretreatment with neutral solvent generated valuable leachate, showed significant impact on the ash extraction, pyrolysis oil yield, and its composition and therefore can be regarded as more appropriate for thermochemical conversion of Napier grass