1,432 research outputs found

    Human papillomavirus status in southern Chinese women

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    1. The overall and type-specific human papillomavirus (HPV) prevalence differed between Hong Kong and Guangzhou healthy women. The prevalence of HPV was significantly higher in Guangzhou than Hong Kong women. Younger women had significantly higher risk of HPV infection. 2. HPV16 remained the most common type detected in both regions; the frequency increased with increasing disease severity. The prevalence of HPV58 and HPV52 was relatively high in women with normal cervix and precancerous lesions.published_or_final_versio

    An essential function for the ATR-Activation-Domain (AAD) of TopBP1 in mouse development and cellular senescence

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    ATR activation is dependent on temporal and spatial interactions with partner proteins. In the budding yeast model, three proteins – Dpb11TopBP1, Ddc1Rad9 and Dna2 - all interact with and activate Mec1ATR. Each contains an ATR activation domain (ADD) that interacts directly with the Mec1ATR:Ddc2ATRIP complex. Any of the Dpb11TopBP1, Ddc1Rad9 or Dna2 ADDs is sufficient to activate Mec1ATR in vitro. All three can also independently activate Mec1ATR in vivo: the checkpoint is lost only when all three AADs are absent. In metazoans, only TopBP1 has been identified as a direct ATR activator. Depletion-replacement approaches suggest the TopBP1-AAD is both sufficient and necessary for ATR activation. The physiological function of the TopBP1 AAD is, however, unknown. We created a knock-in point mutation (W1147R) that ablates mouse TopBP1-AAD function. TopBP1-W1147R is early embryonic lethal. To analyse TopBP1-W1147R cellular function in vivo, we silenced the wild type TopBP1 allele in heterozygous MEFs. AAD inactivation impaired cell proliferation, promoted premature senescence and compromised Chk1 signalling following UV irradiation. We also show enforced TopBP1 dimerization promotes ATR-dependent Chk1 phosphorylation. Our data suggest that, unlike the yeast models, the TopBP1-AAD is the major activator of ATR, sustaining cell proliferation and embryonic development

    AFLP analysis on genetic diversity and population structure of small yellow croaker Larimichthys polyactis

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    The population genetic structure and diversity of small yellow croaker Larimichthys polyactis in the Bohai Bay, Yellow Sea and East China Sea were analyzed using amplified fragment length polymorphism(AFLP). Ninety-one individuals were collected from six locations representing three stocks of small yellow croaker. A total of 218 putative loci were detected by 3 primer combinations, 148 of which were polymorphic (67.89%). The proportion of polymorphic loci and Nei’s genetic diversity for six populations ranged from 55.34 - 60.09%, and from 0.1244 - 0.1378. AMOVA analysis and pairwise FST revealedsignificant genetic differentiation among the three groups based on the breeding migration routes and over-wintering grounds, supporting separate stocks in this species. The result shows the migratorybehavior might be an important factor which influences the genetic structure of this species. The UPGMA tree also revealed the significant geographic structure in this species. Pattern of isolation bydistance was observed in this species, indicating that significant genetic differentiation among localities of small yellow croaker might be due to the geographic distance

    Celecoxib exerts protective effects in the vascular endothelium via COX-2-independent activation of AMPK-CREB-Nrf2 signalling

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    Although concern remains about the athero-thrombotic risk posed by cyclo-oxygenase (COX)-2-selective inhibitors, recent data implicates rofecoxib, while celecoxib appears equivalent to NSAIDs naproxen and ibuprofen. We investigated the hypothesis that celecoxib activates AMP kinase (AMPK) signalling to enhance vascular endothelial protection. In human arterial and venous endothelial cells (EC), and in contrast to ibuprofen and naproxen, celecoxib induced the protective protein heme oxygenase-1 (HO-1). Celecoxib derivative 2,5-dimethyl-celecoxib (DMC) which lacks COX-2 inhibition also upregulated HO-1, implicating a COX-2-independent mechanism. Celecoxib activated AMPKα(Thr172) and CREB-1(Ser133) phosphorylation leading to Nrf2 nuclear translocation. Importantly, these responses were not reproduced by ibuprofen or naproxen, while AMPKα silencing abrogated celecoxib-mediated CREB and Nrf2 activation. Moreover, celecoxib induced H-ferritin via the same pathway, and increased HO-1 and H-ferritin in the aortic endothelium of mice fed celecoxib (1000 ppm) or control chow. Functionally, celecoxib inhibited TNF-α-induced NF-κB p65(Ser536) phosphorylation by activating AMPK. This attenuated VCAM-1 upregulation via induction of HO-1, a response reproduced by DMC but not ibuprofen or naproxen. Similarly, celecoxib prevented IL-1β-mediated induction of IL-6. Celecoxib enhances vascular protection via AMPK-CREB-Nrf2 signalling, a mechanism which may mitigate cardiovascular risk in patients prescribed celecoxib. Understanding NSAID heterogeneity and COX-2-independent signalling will ultimately lead to safer anti-inflammatory drugs

    Many-shot from Low-shot: Learning to Annotate using Mixed Supervision for Object Detection

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    Object detection has witnessed significant progress by relying on large, manually annotated datasets. Annotating such datasets is highly time consuming and expensive, which motivates the development of weakly supervised and few-shot object detection methods. However, these methods largely underperform with respect to their strongly supervised counterpart, as weak training signals \emph{often} result in partial or oversized detections. Towards solving this problem we introduce, for the first time, an online annotation module (OAM) that learns to generate a many-shot set of \emph{reliable} annotations from a larger volume of weakly labelled images. Our OAM can be jointly trained with any fully supervised two-stage object detection method, providing additional training annotations on the fly. This results in a fully end-to-end strategy that only requires a low-shot set of fully annotated images. The integration of the OAM with Fast(er) R-CNN improves their performance by 17%17\% mAP, 9%9\% AP50 on PASCAL VOC 2007 and MS-COCO benchmarks, and significantly outperforms competing methods using mixed supervision.Comment: Accepted at ECCV 2020. Camera-ready version and Appendice

    On the Link between the Subseasonal Evolution of the North Atlantic Oscillation and East Asian Climate

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    We analyse the impact of the North Atlantic Oscillation (NAO) on the climate of East Asia at subseasonal time scales during both winter and summer. These teleconections have mainly been investigated at seasonal and longer time scales, while higher-frequency links are largely unexplored. The NAO is defined using extended empirical orthogonal functions on pentad-mean observations, which allows to elucidate the oscillation’s spatial and temporal evolution and clearly separate the development and decay phases. The downstream dynamical imprint and associated temperature and precipitation anomalies are quantified by means of a linear regression analysis. It is shown that the NAO generates a significant climate response over East Asia during both the dry and wet seasons, whose spatial pattern is highly dependent on the phase of the NAO’s life cycle. Temperature and precipitation anomalies develop concurrently with the NAO mature phase, and reach maximum amplitude 5–10 days later. These are shown to be systematically related to mid and high-latitude teleconnections across the Eurasian continent via eastward-propagating quasi-stationary Rossby waves instigated over the Atlantic and terminating in the northeastern Pacific. These findings underscore the importance of rapidly evolving dynamical processes in governing the NAO’s downstream impacts and teleconnections with East Asia.</p
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