710 research outputs found

    Statistical Study of the Relationship Between Ion Upflow and Field-Aligned Current in the Topside Ionosphere for Both Hemispheres During Geomagnetic Disturbed and Quiet Time

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    A statistical study of ion upflow and field‐aligned currents (FACs) has been performed in the topside ionosphere of both hemispheres for magnetic quiet and disturbed times by using DMSP satellite observations from 2010–2013. Distributions in MLT/MLat reveal that ion upflow occurrence shows a dawn‐dusk asymmetry distribution that matches well with the Region 1 FACs. In addition, there are highest occurrence regions near noon and within the midnight auroral disturbance area, corresponding to dayside cusp and nightside auroral disturbance regions, respectively. Both the ion upflow occurrence and FAC regions expand equatorward to a wider area during disturbed times.publishedVersio

    Regulation of subcellular location and activity of Cdc2-cyclinb1 is involved in bendamustine-induced G2 arrest

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    Bendamustine is a multifunctional alkylating agent for the treatment of multiple myeloma, with the G2/M arrest-induction ability in human multiple myeloma RPMI-8226 cells, but the mechanism remains ambiguous. In this study, we found bendamustine caused the G2 arrest in 24 h, regulated the phosphorylation status of Cdc2, and blocked the nuclear import of Cdc2-CyclinB1 complex. Pretreatment with ATM/ATR inhibitor caffeine or p38 MAPK inhibitor SB203580 suppressed the phosphorylation of Cdc2 at Thr14/Tyr15 or attenuate the blockade of nuclear import, respectively; however, neither of these two inhibitors nor the combination imposed significant effects on Bendamustine-triggered G2 arrest. Bendamustine-induced blockade of the nuclear translocation dissipated after 48 h, after which, the G2 arrest was maintained through the inhibitory phosphorylation of Cdc2. Taken together, our research suggested that two or more pathways and mechanisms which regulated the cell cycle in a time-dependent manner were involved in the G2 arrest invoked by bendamustine.Colegio de Farmacéuticos de la Provincia de Buenos Aire

    A genetic study and meta-analysis of the genetic predisposition of prostate cancer in a Chinese population.

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    Prostate cancer predisposition has been extensively investigated in European populations, but there have been few studies of other ethnic groups. To investigate prostate cancer susceptibility in the under-investigated Chinese population, we performed single-nucleotide polymorphism (SNP) array analysis on a cohort of Chinese cases and controls and then meta-analysis with data from the existing Chinese prostate cancer genome-wide association study (GWAS). Genotyping 211,155 SNPs in 495 cases and 640 controls of Chinese ancestry identified several new suggestive Chinese prostate cancer predisposition loci. However, none of them reached genome-wide significance level either by meta-analysis or replication study. The meta-analysis with the Chinese GWAS data revealed that four 8q24 loci are the main contributors to Chinese prostate cancer risk and the risk alleles from three of them exist at much higher frequencies in Chinese than European populations. We also found that several predisposition loci reported in Western populations have different effect on Chinese men. Therefore, this first extensive single-nucleotide polymorphism study of Chinese prostate cancer in comparison with European population indicates that four loci on 8q24 contribute to a great risk of prostate cancer in a considerable large proportion of Chinese men. Based on those four loci, the top 10% of the population have six- or two-fold prostate cancer risk compared with men of the bottom 10% or median risk respectively, which may facilitate the design of prostate cancer genetic risk screening and prevention in Chinese men. These findings also provide additional insights into the etiology and pathogenesis of prostate cancer.This work was conducted on behalf of the CHIPGECS and The PRACTICAL consortia (see Supplementary Consortia). We acknowledge the contribution of doctors, nurses and postgraduate research students at the CHIPGENCS sample collecting centers. We thank Orchid and Rosetrees for funding support. This work was also supported by National Natural Science foundation of China for funding support to H Zhang (Grant No: 30671793 and 81072377), N Feng (Grant No: 81272831), X Zhang (Grant No: 30572139, 30872924 and 81072095), S Zhao (Grant No: 81072092 and 81328017), Y Yu (Grant No: 81172448) and Program for New Century Excellent Talents in University from Department of Education of China (NCET-08-0223) and the National High Technology Research and Development Program of China (863 Program 2012AA021101) to X Zhang.This is the final version of the article. It first appeared from Impact Journals via http://dx.doi.org/10.18632/oncotarget.725

    Roles of MAPK and Spindle Assembly Checkpoint in Spontaneous Activation and MIII Arrest of Rat Oocytes

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    Rat oocytes are well known to undergo spontaneous activation (SA) after leaving the oviduct, but the SA is abortive with oocytes being arrested in metaphase III (MIII) instead of forming pronuclei. This study was designed to investigate the mechanism causing SA and MIII arrest. Whereas few oocytes collected from SD rats at 13 h after hCG injection that showed 100% of mitogen-activated protein kinase (MAPK) activities activated spontaneously, all oocytes recovered 19 h post hCG with MAPK decreased to below 75% underwent SA during in vitro culture. During SA, MAPK first declined to below 45% and then increased again to 80%; the maturation-promoting factor (MPF) activity fluctuated similarly but always began to change ahead of the MAPK activity. In SA oocytes with 75% of MAPK activities, microtubules were disturbed with irregularly pulled chromosomes dispersed over the spindle and the spindle assembly checkpoint (SAC) was activated. When MAPK decreased to 45%, the spindle disintegrated and chromosomes surrounded by microtubules were scattered in the ooplasm. SA oocytes entered MIII and formed several spindle-like structures by 6 h of culture when the MAPK activity re-increased to above 80%. While SA oocytes showed one Ca2+ rise, Sr2+-activated oocytes showed several. Together, the results suggested that SA stimuli triggered SA in rat oocytes by inducing a premature MAPK inactivation, which led to disturbance of spindle microtubules. The microtubule disturbance impaired pulling of chromosomes to the spindle poles, caused spindle disintegration and activated SAC. The increased SAC activity reactivated MPF and thus MAPK, leading to MIII arrest

    Germline variation at 8q24 and prostate cancer risk in men of European ancestry

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    Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification

    Comparison of Infectious Agents Susceptibility to Photocatalytic Effects of Nanosized Titanium and Zinc Oxides: A Practical Approach

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