1,200 research outputs found

    Asymmetric impact of Atlantic Multidecadal Oscillation on El Nino and La Nina characteristics

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    The long-lasting cold surface conditions of North Atlantic, i.e., the negative phase of Atlantic Multidecadal Oscillation (AMO), can intensify the El Nino-Southern Oscillation through the enhanced air-sea coupling under the increased central-to-eastern tropical Pacific mean sea surface temperature. However, the impact of warmer mean sea surface temperature (SST) is more efficient in the intensifying El Nino than La Nina, because of the nature of the exponential growth of atmospheric convection to SST change. Moreover, the farther eastward shift of the atmospheric convection during the negative AMO leads to the stronger El Nino due to the longer delayed negative feedback by oceanic waves. Therefore, the AMO mainly influences the El Nino intensity rather than La Nina intensity.△1122Ysciescopu

    Cmr1/WDR76 defines a nuclear genotoxic stress body linking genome integrity and protein quality control

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    DNA replication stress is a source of genomic instability. Here we identify ​changed mutation rate 1 (​Cmr1) as a factor involved in the response to DNA replication stress in Saccharomyces cerevisiae and show that ​Cmr1—together with ​Mrc1/​Claspin, ​Pph3, the chaperonin containing ​TCP1 (CCT) and 25 other proteins—define a novel intranuclear quality control compartment (INQ) that sequesters misfolded, ubiquitylated and sumoylated proteins in response to genotoxic stress. The diversity of proteins that localize to INQ indicates that other biological processes such as cell cycle progression, chromatin and mitotic spindle organization may also be regulated through INQ. Similar to ​Cmr1, its human orthologue ​WDR76 responds to proteasome inhibition and DNA damage by relocalizing to nuclear foci and physically associating with CCT, suggesting an evolutionarily conserved biological function. We propose that ​Cmr1/​WDR76 plays a role in the recovery from genotoxic stress through regulation of the turnover of sumoylated and phosphorylated proteins

    TMEM16F activation by Ca2+ triggers plasma membrane expansion and directs PD-1 trafficking

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    TMEM16F is a Ca2+ -gated ion channel that is required for Ca2+ -activated phosphatidylserine exposure on the surface of many eukaryotic cells. TMEM16F is widely expressed and has roles in platelet activation during blood clotting, bone formation and T cell activation. By combining microscopy and patch clamp recording we demonstrate that activation of TMEM16F by Ca2+ ionophores in Jurkat T cells triggers large-scale surface membrane expansion in parallel with phospholipid scrambling. With continued ionophore application,TMEM16F-expressing cells then undergo extensive shedding of ectosomes. The T cell co-receptor PD-1 is selectively incorporated into ectosomes. This selectivity depends on its transmembrane sequence. Surprisingly, cells lacking TMEM16F not only fail to expand surface membrane in response to elevated cytoplasmic Ca2+, but instead undergo rapid massive endocytosis with PD-1 internalisation. These results establish a new role for TMEM16F as a regulator of Ca2+ activated membrane trafficking

    Hepatitis B vaccinations among Koreans: Results from 2005 Korea National Cancer Screening Survey

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    <p>Abstract</p> <p>Background</p> <p>Liver cancer is one of most commonly diagnosed cancers among Koreans. Chronic hepatitis B virus (HBV) infection is a major risk factor for liver cancer. HBV infection can be prevented by effective screening and vaccination programs. The purpose of this study is to examine the status of HBV infection and the predictors associated with HBV vaccination.</p> <p>Methods</p> <p>The study population was derived from the 2005 Korea National Cancer Screening Survey (KNCSS). The KNCSS is an annual cross-sectional survey that uses a nationally-representative random sampling to investigate cancer screening rates. A total of 1,786 Koreans over 40 years of age participated in this study.</p> <p>Results</p> <p>Of all the participants, 5.9% reported HBV positive (HBsAg+, HBsAb-), 41.8% were HBV negative but protected (HBsAg-, HBsAb+), and 52.3% were unprotected (HBsAg-, HBsAb-). Among unprotected individuals (n = 934), 23.1% reported to have received the vaccination. About half of those who had vaccinations completed the 3-shot vaccine series. In multiple analyses, education, having private cancer insurance, alcohol use, having regular check-up, and doing regular exercise were associated with completed HBV vaccination.</p> <p>Conclusion</p> <p>This study result suggests that we need a liver cancer education program to increase HBV awareness and to increase the liver cancer prevention message among low educated populations.</p

    Differential involvement of trigeminal transition zone and laminated subnucleus caudalis in orofacial deep and cutaneous hyperalgesia: the effects of interleukin-10 and glial inhibitors

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    <p>Abstract</p> <p>Background</p> <p>In addition to caudal subnucleus caudalis (Vc) of the spinal trigeminal complex, recent studies indicate that the subnuclei interpolaris/caudalis (Vi/Vc) transition zone plays a unique role in processing deep orofacial nociceptive input. Studies also suggest that glia and inflammatory cytokines contribute to the development of persistent pain. By systematically comparing the effects of microinjection of the antiinflammatory cytokine interleukin (IL)-10 and two glial inhibitors, fluorocitrate and minocycline, we tested the hypothesis that there was a differential involvement of Vi/Vc and caudal Vc structures in deep and cutaneous orofacial pain.</p> <p>Results</p> <p>Deep or cutaneous inflammatory hyperalgesia, assessed with von Frey filaments, was induced in rats by injecting complete Freund's adjuvant (CFA) into the masseter muscle or skin overlying the masseter, respectively. A unilateral injection of CFA into the masseter or skin induced ipsilateral hyperalgesia that started at 30 min, peaked at 1 d and lasted for 1-2 weeks. Secondary hyperalgesia on the contralateral site also developed in masseter-, but not skin-inflamed rats. Focal microinjection of IL-10 (0.006-1 ng), fluorocitrate (1 μg), and minocycline (0.1-1 μg) into the ventral Vi/Vc significantly attenuated masseter hyperalgesia bilaterally but without an effect on hyperalgesia after cutaneous inflammation. Injection of the same doses of these agents into the caudal Vc attenuated ipsilateral hyperalgesia after masseter and skin inflammation, but had no effect on contralateral hyperalgesia after masseter inflammation. Injection of CFA into the masseter produced significant increases in N-methyl-D-aspartate (NMDA) receptor NR1 serine 896 phosphorylation and glial fibrillary acidic protein (GFAP) levels, a marker of reactive astrocytes, in Vi/Vc and caudal Vc. In contrast, cutaneous inflammation only produced similar increases in the Vc.</p> <p>Conclusion</p> <p>These results support the hypothesis that the Vi/Vc transition zone is involved in deep orofacial injury and suggest that glial inhibition and interruption of the cytokine cascade after inflammation may provide pain relief.</p

    Expression of cytokine and chemokine mRNA and secretion of tumor necrosis factor-α by gallbladder epithelial cells: Response to bacterial lipopolysaccharides

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    BACKGROUND: In addition to immune cells, many other cell types are known to produce cytokines. Cultured normal mouse gallbladder epithelial cells, used as a model system for gallbladder epithelium, were examined for their ability to express the mRNA of various cytokines and chemokines in response to bacterial lipopolysaccharide. The synthesis and secretion of the tumor necrosis factor-α (TNF-α) protein by these cells was also measured. RESULTS: Untreated mouse gallbladder cells expressed mRNA for TNF-α, RANTES, and macrophage inflammatory protein-2 (MIP-2). Upon treatment with lipopolysaccharide, these cells now produced mRNA for Interleukin-1β (IL-1β), IL-6, monocyte chemoattractant protein-1 (MCP-1), and showed increased expression of TNF-α and MIP-2 mRNA. Untreated mouse gallbladder cells did not synthesize TNF-α protein; however, they did synthesize and secrete TNF-α upon treatment with lipopolysaccharide. METHODS: Cells were treated with lipopolysaccharides from 3 strains of bacteria. Qualitative and semi-quantitative RT-PCR, using cytokine or chemokine-specific primers, was used to measure mRNA levels of TNFα, IL-1β, IL-6, IL-10, KC, RANTES, MCP-1, and MIP-2. TNF-α protein was measured by immunoassays. CONCLUSION: This research demonstrates that gallbladder epithelial cells in response to lipopolysaccharide exposure can alter their cytokine and chemokine RNA expression pattern and can synthesize and secrete TNFα protein. This suggests a mechanism whereby gallbladder epithelial cells in vivo may mediate gallbladder secretory function, inflammation and diseases in an autocrine/paracrine fashion by producing and secreting cytokines and/or chemokines during sepsis

    Correlation between Discharged Worms and Fecal Egg Counts in Human Clonorchiasis

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    Clonorchiasis is a major neglected disease in East Asia. Worm data in infected humans are very limited, and only egg counts roughly estimate infection burden of the worms. In endemic areas, we recruited infected cases and tried to collect the adult worms from them. They were treated with 3 doses of praziquantel, and purged next day under fasting. Adult worms of C. sinensis were recovered from their diarrheal feces. The worms discharged from humans after treatment are minimum confirmed numbers. The worm recovery rate noticeably increased in subjects with higher egg counts. The number of collected worms was well-correlated with the egg counts. Worm collection by praziquantel medication and purgation is a safe non-invasive method to get worm information from human. The present study confirms that at least 110 worms are infected in a human body with egg counts per gram of feces around 3,000, and egg productivity of a worm per day is around 4,000
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