CpG联合铝佐剂对HCV免疫原体液免疫作用的影响

目的:探讨胞苷酸鸟苷寡脱氧核苷酸(CpG ODN)联合铝佐剂对丙型肝炎病毒(HCV)重组免疫原的体液免疫作用。方法:采用高交叉HCV-HVR1和E1重组蛋白与CpG ODN、铝佐剂组合,免疫BALB/c小鼠后以ELISA、酶联免疫斑点测定、流式细胞术、免疫沉淀等方法检测相关体液免疫指标和免疫血清多抗的交叉反应性。结果:CpG联合铝佐剂激发了最高的特异性抗体滴度;佐剂通过提高抗体分泌细胞数量、增加脾脏中记忆B细胞数量、增加脾淋巴细胞IL-6、IL-10分泌浓度实现体液免疫增效;CpG则能提高免疫效率,联合铝佐剂时显著提高浆细胞数量;12份HCV阳性血清中有10份可与多抗HVR1 IgG发生免疫沉淀。结论:CpG和铝佐剂联合应用具有协同作用,多抗HVR1 IgG具有较好的交叉反应性。     

Forecasting the effects of global change scenarios on bioaccumulation patterns in great lakes species

Climate change will have substantial impacts on biodiversity, particularly for aquatic species. Warming temperatures and changing weather patterns will also remobilize and modify chemical partitioning. Holding millions of cubic yards of sediments contaminated with persistent legacy chemicals such as polychlorinated biphenyls (PCBs) and dioxins, the Laurentian Great Lakes are a laboratory for observing interactions between biological and chemical responses to climate change. They provide a wide range of habitat to a variety of species, from littoral forage fish to deep‐water predators. In this paper, we couple bioenergetic and bioaccumulation models to investigate the biological and chemical effects of climate change in the Great Lakes. We consider three species: round goby, a warm‐water invasive forage fish; mottled sculpin, a cool‐water native forage fish; and lake trout, a cold‐water native predator. Using our coupled models, we calculate the accumulation of a representative persistent chemical, PCB‐77, under four climate scenarios for Lake Erie and Lake Superior. Predator–prey (lake trout–round goby) interactions and food availability (high–low) are incorporated into our simulations. For cool‐ to cold‐water species (sculpin, lake trout) we find that warm temperatures limit growth. For warm‐water species (round goby) cold temperatures limit growth. The impact of climate warming on growth depends on the winter lows as well as the summer highs of the scenario, in combination with the species' critical upper and lower thermal limits. We find conditions for high growth and consumption rates generally lead to high bioaccumulation. However, this can be confounded by predator–prey dynamics, as mismatches in the temperature preferences of predator and prey can lead to mismatches in relative growth and uptake rates. As predator–prey dynamics are expected to undergo substantial shifts with changing climate, these relative thermal sensitivities will be key in determining the implications of climate change for bioaccumulation, particularly in top predator species.     

Spectral properties of a long-wavelength absorbing form of protochlorophyll in seeds of Cyclanthera explodens

The in vivo absorbance spectrum of the inner seed coat of Cyclanthera explodens Naud. showed a main peak in the red region at 671 nm and a weak shoulder at about 640 nm. The pigments were extracted with acetone. separated by paper chromatography and analysed spectrophotometrically. The only detectable pigment was protochlorophyll. The in vivo fluorsecence emission spectra had two main peaks, one at 632 and one at 691 nm. The relation between the two peaks was changed when the exvcitation wavelength was altered from 440 to 460 nm. Excitation at 420 nm gave an additional fluorescence emission peak at 595 nm. These data indicate the presence of at least three forms of protochlorophyll in the Cyclantera seed coat. The spectrum of circular dichroism had a very intence and characteristic signal in the red region with a negative asymmetrical Cotton effect (664 (+), 669 (0) and 687 (?) nm). This indicates that at least one of the protochlorophyll forms is present in a more or less crystalline form.     

The Role of Anaerobic Respiration in Germinating Muskmelon Seeds: I. IN RELATION TO SEED LOT QUALITY

Five muskmelon (Cucumis melo L.) cultivar seedlots from a commercialsource and freshly produced seeds of two cultivars, when artificiallyaged, were found to differ in their viability and vigour asdetermined by germination tests. Furthermore, the various commercialseedlots without ageing also exhibit a range of deteriorationlevels. Low vigour seeds had higher respiratory quotient valuesthan the high vigour seeds as a result of a higher level ofCO₂ production. This high level of CO₂ evolution in low vigourseeds may have been due to anaerobic respiration. Levels of acetaldehyde and ethanol produced by imbibing seedswere negatively associated with seed viability and vigour. After6 h of imbibition low vigour seeds produced significantly moreethanol and acetaldehyde than high vigour seeds. After 24 hof imbibition, ethanol continued to accumulate in the commercialseedlots up to 10-fold the amount produced after 6 h of imbibition,whereas, acetaldehyde levels increased less. However, in thefreshly produced, artificially aged seeds (except the most extremeageing), ethanol levels were reduced and no acetaldehyde productioncould be detected, indicating re-utilization of ethanol. It is suggested that ethanol production in the first hours ofimbibition can be used as a reliable index to predict germinationin muskmelon seedlots. Key words: Germination, Cucumis melo L., Seeds, Anaerobic respiration     

Discovery of disubstituted phenanthrene imidazoles as potent,selective and orally active mPGES-1 inhibitors

Phenanthrene imidazoles 26 and 44 have been identified as novel potent, selective and orally active mPGES-1 inhibitors. These inhibitors are significantly more potent than the previously reported chlorophenanthrene imidazole 1 (MF63) with a human whole blood IC₅₀ of 0.20 and 0.14 μM, respectively. It exhibited a significant analgesic effect in a guinea pig hyperalgesia model at oral doses as low as 14 mg/kg. Both active and selective mPGES-1 inhibitors (26 and 44) have a relatively distinct pharmacokinetic profile and are suitable for clinical development.     

Combined effect of repetitive work and cold on muscle function and fatigue.

This study compared the effect of repetitive work in thermoneutral and cold conditions on forearm muscle electromyogram (EMG) and fatigue. We hypothesize that cold and repetitive work together cause higher EMG activity and fatigue than repetitive work only, thus creating a higher risk for overuse injuries. Eight men performed six 20-min work bouts at 25 degrees C (W-25) and at 5 degrees C while exposed to systemic (C-5) and local cooling (LC-5). The work was wrist flexion-extension exercise at 10% maximal voluntary contraction. The EMG activity of the forearm flexors and extensors was higher during C-5 (31 and 30%, respectively) and LC-5 (25 and 28%, respectively) than during W-25 (P < 0.05). On the basis of fatigue index (calculated from changes in maximal flexor force and flexor EMG activity), the fatigue in the forearm flexors at the end of W-25 was 15%. The corresponding values at the end of C-5 and LC-5 were 37% (P < 0.05 in relation to W-25) and 20%, respectively. Thus repetitive work in the cold causes higher EMG activity and fatigue than repetitive work in thermoneutral conditions.     

Occurrence of Peronospora sparsa (P. rubi) on cultivated and wild Rubus species in Finland and Sweden

An outbreak of a dryberry disease caused by Peronospora sparsa (syn. P. rubi) occurred in plantations of arctic bramble (Rubus arcticus subsp. arcticus) in Finland in the middle of 1990s. The disease persists and is most severe in cool and rainy summers. The disease has not been encountered in northern Sweden where cultivars (R. arcticus nothosubsp. stellarcticus) different from those in Finland are used. The occurrence of P. sparsa in wild Rubus spp. is virtually unknown in both areas and it is not known whether they constitute a potential infection source. Therefore, the aim of this study was to investigate the occurrence of P. sparsa on wild Rubus spp. growing in the vicinity of cultivations of arctic bramble. Symptomatic plants were sampled in 1997–1999. P. sparsa was detected using a light microscope, preceded by incubation of the sample in vitro if necessary, and by a polymerase chain reaction (PCR) based method. Plants of cultivated R. arcticus subsp. arcticus were commonly infected by P. sparsa in Finland. P. sparsa was also found on the cultivated R. arcticus nothosubsp. stellarcticus in Finland and Sweden. However, the infected plants of the cultivars of nothosubsp. stellarcticus seemed to be much less damaged than the cultivars of subsp. arcticus. Plants infected with P. sparsa were found in the populations of wild R. arcticus subsp. arcticus in both countries, and in cloudberry (R. chamaemorus) in natural habitats in Finland. In addition, P. sparsa was detected on specimens of R. arcticus subsp. arcticus (collected in 1966–1985) and R. chamaemorus (collected in 1899–1981) in Finnish herbaria. The samples of R. idaeus and R. saxatilis collected from the field in this study or investigated in the herbaria were not infected with P. sparsa. These data show that P. sparsa has not recently invaded Finland but has become an economically significant pathogen during the rapid expansion of cultivation of the apparently sensitive clones of arctic bramble.     

Synthesis and structure--activity relationship of novel aminotetralin derivatives with high micro selective opioid affinity

Several novel racemic aminotetralin derivatives have been prepared using a stereoselective aziridine ring opening reactions and were evaluated for their micro-opioid receptor binding affinity. Selectivity index towards other opioid receptors and antinociceptive activity in mice have been evaluated for the most potent derivatives.     

Trisubstituted ureas as potent and selective mPGES-1 inhibitors

A novel series of trisubstituted ureas has been identified as potent and selective mPGES-1 inhibitors. These compounds are selective over other prostanoid enzymes such as PGF synthase and TX synthase. This series of inhibitors was developed by lead optimization of a hit from an internal HTS campaign. Lead compound 42 is potent in A549 cell assay (IC₅₀ of 0.34 μM) and in human whole blood assay (IC₅₀ of 2.1 μM). An efficient and versatile one-pot strategy for the formation of ureas, involving a reductive amination, was developed to generate these inhibitors.