Rhinoviral infections activate p38MAP-kinases via membrane rafts and RhoA.

Rhinoviral infections belong to the most frequent human infections characterized by common cold, chronic bronchitis, exacerbations of asthma, otitis media and sinusitis. Here, we define molecular mechanisms that mediate infections of human epithelial cells with human rhinovirus strain 14 (RV14). We demonstrate that RV14 activates p38-MAPKinase (p38-K) in a biphasic time course. Early stimulation of p38-K by RV14 was observed a few minutes after initiation of the infection, while the late increase of p38-K activity occurred 7-12 hrs upon infection. The stimulation of p38-K was mediated by the small G-protein RhoA,which was activated by RV14. Transfection of a genetic construct preventing RhoA activation blocked RV14-induced p38-K activation. Further, integrity of cholesterol and sphingolipid-enriched membrane domains was required for RV14-mediated p38-K activation, which was inhibited by destruction of membrane rafts. The data indicate that RV employs a signaling cascade from membrane rafts via the small G-protein RhoA to p38-K to infect human cells.     

拐芹根化学成分研究Ⅱ

从伞型科当归属植物拐芹(Angelica polymorpha Maxim)的根及根茎中又分得4个结晶性化合物。经物理常数测定、光谱分析,分别鉴定为欧前胡素Ⅰ,异氧化前胡内酯Ⅱ,Pabulenol Ⅲ,Phellopterin Ⅳ。     

Bacterioplankton Dynamics in the McMurdo Dry Valley Lakes, Antarctica: Production and Biomass Loss over Four Seasons

Abstract Research of the microbial ecology of McMurdo Dry Valley lakes has concentrated primarily on phototrophs; relatively little is known about the heterotrophic bacterioplankton. Bacteria represent a substantial proportion of water column biomass in these lakes, comprising 30 to 60% of total microplankton biomass. Bacterial production and cell numbers were measured 3 to 5 times, within four Antarctic seasons (October to January), in Lakes Fryxell, Hoare, and Bonney. The winter-spring transition (September to October) was included during one year. Lake Fryxell was the most productive, but variable, lake, followed by Lakes Bonney and Hoare. Bacterial production ranged from 0 to 0.009 μg C ml-1 d-1; bacterial populations ranged from 3.2 x 10(4) to 4.4 x 10(7) cells ml-1. Bacterial production was always greatest just below the ice cover at the beginning of the season. A second maximum developed just above the chemocline of all the lakes, as the season progressed. Total bacterioplankton biomass in the lakes decreased as much as 88% between successive sampling dates in the summer, as evidenced by areal integration of bacterial populations; the largest decreases in biomass typically occurred in mid-December. A forward difference model of bacterial loss in the trophogenic zone and the entire water column of these lakes showed that loss rates in the summer reached 6.3 x 10(14) cells m-2 d-1 and 4.16 x 10(12) cells m-2 d-1, respectively. These results imply that bacteria may be a source of carbon to higher trophic levels in these lakes, through grazing.     

Ceramide metabolism determines glioma cell resistance to chemotherapy

Tumor cell resistance to chemotherapy constitutes a major problem in the treatment of malignant tumors. We here investigated the role of ceramide metabolism for the resistance of glioma cells to treatment with the chemotherapeutic drug, gemcitabine. Gemcitabine triggers a marked release of ceramide in drug‐sensitive cells, while glioma cells that are resistant to gemcitabine, fail to accumulate ceramide. While the release of ceramide is very similar in gemcitabine‐sensitive and resistant glioma cells upon stimulation, resistant glioma cells rapidly consume ceramide upon gemcitabine treatment or exogenous sphingomyelinase stimulation. Pharmacologic or genetic inhibition of glucosyltransferases prevents ceramide consumption in resistant cells and restores sensitivity of resistant glioma cells to gemcitabine. These data suggest that glioma cell resistance to at least some chemotherapeutic drugs is mediated by rapid consumption of ceramide to prevent cell death. J. Cell. Physiol. 221: 688–695, 2009. © 2009 Wiley‐Liss, Inc.     

TNF-alpha induction by LPS is regulated posttranscriptionally via a Tpl2/ERK-dependent pathway

Tpl2 knockout mice produce low levels of TNF-alpha when exposed to lipopolysaccharide (LPS) and they are resistant to LPS/D-Galactosamine-induced pathology. LPS stimulation of peritoneal macrophages from these mice did not activate MEK1, ERK1, and ERK2 but did activate JNK, p38 MAPK, and NF-kappaB. The block in ERK1 and ERK2 activation was causally linked to the defect in TNF-alpha induction by experiments showing that normal murine macrophages treated with the MEK inhibitor PD98059 exhibit a similar defect. Deletion of the AU-rich motif in the TNF-alpha mRNA minimized the effect of Tpl2 inactivation on the induction of TNF-alpha. Subcellular fractionation of LPS-stimulated macrophages revealed that LPS signals transduced by Tpl2 specifically promote the transport of TNF-alpha mRNA from the nucleus to the cytoplasm.     

Esophageal telocytes and hybrid morphologies

TCs (telocytes) are actually defined as stromal cells with specific long and thin prolongations, called Tp (telopodes). They have been positively identified in various tissues and we now report their presence in the esophagus. These cells were identified by TEM (transmission electron microscopy) in esophageal samples of Wistar rats (n = 5) occurring beneath the basal epithelial layer, in submucosa, closely related to smooth and striated muscular fibres, as also in the adventitia. They are closely related to mast cells, macrophages and microvessels. Hybrid morphologies of stromal cells processes were found: cytoplasmic processes continued distally in a telopodial fashion. Telopodes alone may not be sufficient, however, for a safe diagnosis of TCs in TEM. A larger set of specific standards (such as the telopodial emergence, and the size of the cell body and telopodes) should be considered to differentiate TCs from various species of fibroblasts. The morphological and ultrastructural features should distinguish between TCs and interstitial cells of Cajal in the digestive tract.