Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence

Morphine is a powerful pain reliever, but also a potent inducer of tolerance and dependence. The development of opiate tolerance occurs on continued use of the drug such that the amount of drug required to elicit pain relief must be increased to compensate for diminished responsiveness. In many systems, decreased responsiveness to agonists has been correlated with the desensitization of G-protein-coupled receptors. In vitro evidence indicates that this process involves phosphorylation of G-protein-coupled receptors and subsequent binding of regulatory proteins called beta-arrestins. Using a knockout mouse lacking beta-arrestin-2 (beta arr2-/-), we have assessed the contribution of desensitization of the mu-opioid receptor to the development of morphine antinociceptive tolerance and the subsequent onset of physical dependence. Here we show that in mice lacking beta-arrestin-2, desensitization of the mu-opioid receptor does not occur after chronic morphine treatment, and that these animals fail to develop antinociceptive tolerance. However, the deletion of beta-arrestin-2 does not prevent the chronic morphine-induced up-regulation of adenylyl cyclase activity, a cellular marker of dependence, and the mutant mice still become physically dependent on the drug.     

Sonic hedgehog signaling pathway in vertebrate epithelial appendage morphogenesis: perspectives in development and evolution

Vertebrate epithelial appendages are elaborate topological transformations of flat epithelia into complex organs that either protrude out of external (integument) and internal (oral cavity, gut) epithelia, or invaginate into the surrounding mesenchyme. Although they have specific structures and diverse functions, most epithelial appendages share similar developmental stages, including induction, morphogenesis, differentiation and cycling. The roles of the SHH pathway are analyzed in exemplary organs including feather, hair, tooth, tongue papilla, lung and foregut. SHH is not essential for induction and differentiation, but is involved heavily in morphogenetic processes including cell proliferation (size regulation), branching morphogenesis, mesenchymal condensation, fate determination (segmentation), polarizing activities and so on. Through differential activation of these processes by SHH in a spatiotemporal-specific fashion, organs of different shape and size are laid down. During evolution, new links of developmental pathways may occur and novel forms of epithelial appendages may emerge, upon which evolutionary selections can act. Sites of major variations have progressed from the body plan to the limb plan to the epithelial appendage plan. With its powerful morphogenetic activities, the SHH pathway would likely continue to play a major role in the evolution of novel epithelial appendages.     

Enhancement of monacolin K production via intergeneric protoplast fusion between Aspergillus terreus and Monascus anka

Intergenric protoplast fusion between Aspergillus terreus CA99 and Monascus anka M-3, the high and low producers of monacolin K respectively，was performed for enhancement of monacolin K production. The 24-hour-old mycelia of A. terreus CA99 and M. anka M-3 were treated with 0.5% lywallzyme, 0.3% snailase and 0.3% cellulase at 34℃ for 5 h and at 30℃ for 3.5 h, and their protoplasts formation reached 1.76×10⁷/mL and 1.68×10⁷/mL respectively. Parental protoplasts were irradiated with a 30 W UV light away from 30 cm for 3 min and then mixed. The mixture was incubated with 30% PEG 6000 for 15 min. The reviving fusants were isolated on the regeneration plates. Of the 363 fusants isolated, over 100 showed enhanced monacolin K production compared with the parental strain M. anka M-3. Ten of them produced monacolin K about 1.6-fold of that M.anka M-3 does and the monacolin K titer of two fusants (F49 and F104) increased by about 1-fold. The monacolin K yields of F49 and F104 were 460 μg/mL and 457 μg/mL respectively. In optimized fermentation medium, the monacolin K titer of F49 reached 1216 μg/mL.     

Bow-tie topological features of metabolic networks and the functional significance

Exploring the structural topology of genome-based large-scale metabolic network is essential for in- vestigating possible relations between structure and functionality.Visualization would be helpful for obtaining immediate information about structural organization.In this work,metabolic networks of 75 organisms were investigated from a topological point of view.A spread bow-tie model was proposed to give a clear visualization of the bow-tie structure for metabolic networks.The revealed topological pattern helps to design more efficient algorithm specifically for metabolic networks.This coarse- grained graph also visualizes the vulnerable connections in the network,and thus could have important implication for disease studies and drug target identifications.In addition,analysis on the reciprocal links and main cores in the GSC part of bow-tie also reveals that the bow-tie structure of metabolic networks has its own intrinsic and significant features which are significantly different from those of random networks.     

The experimental study of interaction between shock wave and turbulence

The interaction between shock wave and turbulence has been studied in supersonic turbulent mix layer wind tunnel. The interaction between oblique shock wave and turbulent boundary layer and the influence of large vortex in mix layer on oblique shock wave have been observed by NPLS technique. From NPLS image, not only complex flow structure is observed but also time-dependent supersonic flow visualization is realized. The mechanism of interaction between shock wave and turbulence is discussed based on high quality NPLS image.     

Experimental investigation of incremental reactivity of di-tert-butyl peroxide

Large quantities of di-tert-butyl peroxide (DTBP) have been emitted into the troposphere due to human activities. Its role in the atmospheric photochemical reaction has not been understood. This study presents the results of the photochemical reactions of DTBP and NOx, which have been simulated in a self-made smog chamber under the temperature of (29±1)℃. Both the wall decays of ozone and NO2 could be neglected, compared to the results in simulative experiments. The effective intensity of UV light used in the experiments was 1.28×10-3 s-1, which was expressed by the rate constant of NO2 photolysis in purified air. The reaction mechanism was proposed according to our results and reports of other researchers. The maximum values of incremental reactivity (IR) in the three simulative ex- periments were 9.53×10-2, 5.23×10-2 and 3.78×10-2, respectively. The incremental reactivity decreased with the increase of initial concentrations of DTBP. The IR value of DTBP obtained in this study was comparable to that of acetylene reported in our previous research.     

Enhancement of monacolin K production via intergeneric protoplast fusion between Aspergillus terreus and Monascus anka

Intergenric protoplast fusion between Aspergillus terreus CA99 and Monascus anka M-3, the high and low producers of monacolin K respectively,was performed for enhancement of monacolin K production. The 24-hour-old mycelia of A. terreus CA99 and M. anka M-3 were treated with 0.5% lywallzyme, 0.3% snailase and 0.3% cellulase at 34℃ for 5 h and at 30℃ for 3.5 h, and their protoplasts formation reached 1.76×107/mL and 1.68×107/mL respectively. Parental protoplasts were irradiated with a 30 W UV light away from 30 cm for 3 min and then mixed. The mixture was incubated with 30% PEG 6000 for 15 min. The reviving fusants were isolated on the regeneration plates. Of the 363 fusants isolated, over 100 showed enhanced monacolin K production compared with the parental strain M. anka M-3. Ten of them produced monacolin K about 1.6-fold of that M.anka M-3 does and the monacolin K titer of two fusants (F49 and F104) increased by about 1-fold. The monacolin K yields of F49 and F104 were 460 μg/mL and 457 μg/mL respectively. In optimized fermentation medium, the monacolin K titer of F49 reached 1216 μg/mL.     

Dialdehyde starch nanoparticles： Preparation and application in drub carrier

Dialdehyde starch nanoparticles (DASNP) were prepared by the redox reaction of NaIO4 and starch in water-in-oil microemulsion. IR spectrum showed that DASNP had aldehyde groups, and quantitative alkali consumption showed that its dialdehyde content was about (50±5)%. The average diameter of DASNP determined by SEM was about 100 nm. TGA-DTA showed that its thermal stability was better than starch nanoparticle (StNP) and dialdehyde starch (DAS). Its low biological toxicity was detected by cell experiment. Also the best mass ratio of doxorubicin (DOX) to combined DASNP detected by UV-VIS was 15 : 1, and the product was effective for controlled release of DOX. The cell experiment showed that the drug-carrier particle (DOX-DASNP) can release DOX for a long time and strengthened the effect of the anticancer drug. This work demonstrates that the DASNP, which has good thermal stability, small particle size, low biological toxicity, and slowly anticancer drug-releasing to strengthen drug effect, is a potentially useful carrier for anticancer drug.     

土工合成材料在黄河三角洲地区水利工程上的应用

近年来,随着新技术、新材料的不断出现,地处黄河三角洲地区的胜利石油管理局在水利工程施工中使用了大量的土工合成材料,包括土工布、土工膜、复合土工膜等.通过在水利工程上的不断应用和探索,摸索出了一套适合黄河三角洲地区工程特点的土工合成材料施工方案,取得了较好的社会和经济效益.就土工合成材料在黄河三角洲地区水利工程上的应用作了较详细的介绍.     

Morphological variability and genetic diversity in five species of Skeletonema （Bacillariophyta）

Twelve strains of Skeletonema from Chinese coastal waters and another strain from the West Sea of Korea were examined using light microscopy （LM）, scanning and transmission electron microscopy （SEM, TEM）, and small subunit （SSU） rDNA sequence analysis. We identified four species of Skeletonema： S. marinoi Sarno et Zingone, S. subsalsum （A.Cleve） Bethge, S. dohrnii Sarno et Kooistra, S. trop- icum Cleve, as well as a Skeletonerna-like species. These are the first records of S. rnarinoi, S. dohrnii and S. subsalsurn in China. The Skeletonema-like species, MMDLS067, was isolated from the estuary of the Changjiang River. The morphologic and phylogenetic characteristics of this species are not correspond to those of any previously published Skeletonerna species. The intercalary fultoportula pro- cesses （IFPPs） has long open tubes, and the intercalary rimoportula process （IRP） is short and located inside the rim of the IFPPs. Phylogenetic analysis revealed that MMDL5630 clustered with S. tropicurn in the NJ and MP trees, but its IRPs differed from those of previously described specimens of S. tropicum. The IRP is partially open, with an elongated opening at the base of the tube, and is longer than the IFPPs. Some specimens of S. marinoi and S. dohrnii also have longer tubular IRPs than the IFPPs. Compared to pre- viously described specimens of S. rnar＆oi and S. dohrnii, these two specimens we identified have shorter IRPs. Our results reflect the ambiguity and diversity of Skeletonema taxonomy. They are also significant for the future identification and management of red tides caused by Skeletonerna in the seas around China.