Inactivation of TNF signaling by rationally designed dominant-negative TNF variants

Tumor necrosis factor (TNF) is a key regulator of inflammatory responses and has been implicated in many pathological conditions. We used structure-based design to engineer variant TNF proteins that rapidly form heterotrimers with native TNF to give complexes that neither bind to nor stimulate signaling through TNF receptors. Thus, TNF is inactivated by sequestration. Dominant-negative TNFs represent a possible approach to anti-inflammatory biotherapeutics, and experiments in animal models show that the strategy can attenuate TNF-mediated pathology. Similar rational design could be used to engineer inhibitors of additional TNF superfamily cytokines as well as other multimeric ligands.     

试论呼市地区园林植物五小害虫的发展状况和防治策略

本文在实地调查和试验研究的基础上，系统地分析了呼市地区园林植物五小害虫的发展状况，在初步查清主要危害虫种及其生物学特性基础上，提出了加强植物检疫，利用，保护天敌，加强生物防治的研究，适时采用物理防治方法，合理科学地应用化学防治法的综合防治策略，对化学杀虫剂的选择，使用浓度，施药时间和次数提出了科学有效的试验依据。     

Viral clearance without destruction of infected cells during acute HBV infection

Viral clearance during hepatitis B virus (HBV) infection has been thought to reflect the destruction of infected hepatocytes by CD8(+) T lymphocytes. However, in this study, HBV DNA was shown to largely disappear from the liver and the blood of acutely infected chimpanzees long before the peak of T cell infiltration and most of the liver disease. These results demonstrate that noncytopathic antiviral mechanisms contribute to viral clearance during acute viral hepatitis by purging HBV replicative intermediates from the cytoplasm and covalently closed circular viral DNA from the nucleus of infected cells.     

Functional links between Aβ toxicity, endocytic trafficking, and Alzheimer's disease risk factors in yeast

Aβ (beta-amyloid peptide) is an important contributor to Alzheimer's disease (AD). We modeled Aβ toxicity in yeast by directing the peptide to the secretory pathway. A genome-wide screen for toxicity modifiers identified the yeast homolog of phosphatidylinositol binding clathrin assembly protein (PICALM) and other endocytic factors connected to AD whose relationship to Aβ was previously unknown. The factors identified in yeast modified Aβ toxicity in glutamatergic neurons of Caenorhabditis elegans and in primary rat cortical neurons. In yeast, Aβ impaired the endocytic trafficking of a plasma membrane receptor, which was ameliorated by endocytic pathway factors identified in the yeast screen. Thus, links between Aβ, endocytosis, and human AD risk factors can be ascertained with yeast as a model system.     

Antiproliferative lactams and spiroenone from adlay bran in human breast cancer cell lines

Two new lactams, coixspirolactam D (1) and coixspirolactam E (2), and a new spiroenone, coixspiroenone (3), together with seven known compounds, coixspirolactam A (4), coixspirolactam B (5), coixspirolactam C (6), coixlactam (7), coixol (8), ethyl dioxindole-3-acetate (9), and isoindol-1-one (10), and two neolignans, zhepiresionol (11) and ficusal (12), were isolated from the bioactive subfraction of adlay bran ethanolic extract (ABE). Compounds 9 and 10 are the first isolates from natural resources. The structures of new compounds were identified by spectroscopic methods, including infrared (IR) spectrum, 1D and 2D nuclear magnetic resonance (NMR), and mass spectrum (MS). All of the isolated compounds were tested for antiproliferative effects on MCF-7, MDA-MB-231, and T-47D cells. Results showed that compounds 1, 3, 4, 6, and 7 at 50 μM significantly inhibited MCF-7 cell proliferation by 30.2, 19.2, 21.0, 13.5, and 32.4%, respectively; compounds 2, 4, and 7 significantly inhibited T-47D cells at 50 μM by 20.7, 24.8, and 28.9%; and compounds 1, 2, and 12 significantly inhibited MDA-MB-231 cells at 50 μM by 47.4, 25.3, and 69.3%, respectively. In conclusion, ABE has antiproliferative activities, and this effect is partially related to the presence of lactams and spiroenone.     

Comparison of 1-deoxynojirimycin and aqueous mulberry leaf extract with emphasis on postprandial hypoglycemic effects: in vivo and in vitro studies

Carbohydrate digestion by α-glucosidase and subsequent glucose uptake at the brush border are critical for postprandial blood glucose control. Any specific inhibitors are useful as hyperglycemia modulating agents. In this study, it was postulated that an array of active components in mulberry leaf extract (MLE) may provide higher potency in inhibiting intestinal glucose absorption compared to the single component 1-deoxynojirimycin (DNJ), which is recognized as a promising inhibitor of intestinal glucose absorption. Both MLE and DNJ were active in inhibiting α-glucosidase. However, in Caco-2 cells, only MLE showed significant inhibition of 2-deoxyglucose uptake, whereas DNJ was ineffective. For glucose loading, co-administration of MLE resulted in potent inhibitions of glucose responses compared to those by DNJ in Sprague Dawley (SD) rats, but this was not found for maltose loading. These novel findings add evidence that the unabsorbed phytochemicals in MLE compete with glucose for intestinal glucose transporters, but DNJ itself does not. We also evaluated the timing of MLE consumption. By administering MLE for 30 min before glucose loading, the incremental area under the curve (IAUC) was significantly lowered in the rats, as compared to a simultaneously administered group. Similarly, cellular glucose uptake was significantly reduced in Caco-2 cells following pretreatment.     

On Surface O3 Associated with Long-Range Transport in the Yellow Sea Region

Measurements of surface ozone (O₃) and nitrogen oxides (NO _x ) were conducted at Tae-ahn (TAP) and Chongwon (CHN) on the Korean Peninsula, during the Aerosol Characterization Experiment—Asian Pacific region (ACE-Asia) campaign, March–May 2001. The measurements provide ground-based data at a western remote site of south Korea and characterize the long-range transport of O₃ over the Yellow Sea region during spring. The mean values of O₃ and NO₂ concentration at TAP were 42 ppb and 12 ppb, respectively. The average O₃ diurnal variation of 17 ppb at TAP indicates that the loss of O₃ was not pronounced during the night. The highest NO₂ concentrations, with an average diurnal variation of 8 ppb, occurred in the afternoon at 13–15 LST. The day-to-day variation of daily O₃ concentrations at TAP is strongly influenced by the movement of synoptic scale weather patterns. In general, the O₃ concentration in a southwesterly airflow tended to increase when a moving anticyclone crossed the site, ahead of a cold front. By contrast, north-northwesterly airflows associated with the passage of a cold front bring fresh continental outflow and decrease O₃ concentrations. Surface O₃ data at TAP were classified utilizing backward trajectory analysis based on the residence time, as well as the path of the airflows, in the boundary layer (1500 m asl) over the Yellow Sea region. The results show that north-northwest continental airflows, that were transported around Lake Baikal and eastern Mongolia at an altitude of approximately 3 km at relatively high speed and came straight down at TAP, represent continental background O₃ concentrations with a mean value of 29 ppb for this period. These airflows have a short period of residence of less than one day in the boundary layer over the Yellow Sea region. In contrast, the mean O₃ value of 45 ppb was observed in regionally polluted airflows mainly passing through the east-southeast part of China and remaining for 3 days, on average, in the Yellow Sea region. These three days residence time of the regionally polluted airflows over the Yellow Sea region allowed sufficient time for photochemical O₃ formation.     

Concentration and deposition of trace metals in Ontario-1982

Results of trace metal concentrations in air and precipitation and the corresponding wet and dry deposition in Ontario in 1982 arc reported. In terms of the spatial patterns, in general, there was a decreasing gradient from south-to-north in both concentration and deposition. Patterns differed with each parameter although certain groups of metals (e.g., Fe and Al; Pb, Zn, and Mn) displayed similar patterns. In general, wet deposition was greater than dry deposition at all sites. Geographically, the variability in the wet to dry deposition ratio for coarse particles (MMD > 2.5 μm) was small. However, it increased from the south to the north for fine particles (MMD < 2.5 μm), being higher away from the source areas. Scavenging ratios (W) have been derived from the precipitation and air concentrations of trace metals. The scatter in W is quite large for all trace metals, up to 2 orders of magnitude. There was little seasonal variability in W for fine particles (Pb, Mn, Zn, and Cd). However, coarse particles (Fe, Al, and Cu) were more efficiently scavenged by snow than by rain.