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Tunicamycin, a potent reversible translocase I inhibitor, is produced by several Actinomycetes species. The tunicamycin structure is highly unusual, and contains an 11-carbon dialdose sugar and an α, β-1″,11′-glycosidic linkage. Here we report the identification of a gene cluster essential for tunicamycin biosynthesis by high-throughput heterologous expression (HHE) strategy combined with a bioassay. Introduction of the genes into heterologous non-producing Streptomyces hosts results in production of tunicamycin by these strains, demonstrating the role of the genes for the biosynthesis of tunicamycins. Gene disruption experiments coupled with bioinformatic analysis revealed that the tunicamycin gene cluster is minimally composed of 12 genes (tunAtunL). Amongst these is a putative radical SAM enzyme (Tun B) with a potentially unique role in biosynthetic carbon-carbon bond formation. Hence, a seven-step novel pathway is proposed for tunicamycin biosynthesis. Moreover, two gene clusters for the potential biosynthesis of tunicamycin-like antibiotics were also identified in Streptomyces clavuligerus ATCC 27064 and Actinosynnema mirums DSM 43827. These data provide clarification of the novel mechanisms for tunicamycin biosynthesis, and for the generation of new-designer tunicamycin analogs with selective/enhanced bioactivity via combinatorial biosynthesis strategies.

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Background: Remote ischemic preconditioning (RIPC) of the limb has been shown to induce ischemic tolerance in basic and clinical studies that focused on sustained large artery occlusion rather than small vessel disease (SVD). This study aimed to evaluate the protective effects of brief repetitive limb RIPC on patients with cerebral SVD. Methods: Seventeen patients with cerebral SVD were enrolled. Patients underwent 5 ischemia-reperfusion cycles of preconditioning/sham preconditioning on both upper limbs twice a day for 1 year. Cerebral hemodynamic indexes, brain lesions, cognitive functions and assessment outcomes of dizziness handicap inventory (DHI) were analyzed. Results: In the RIPC group, the mean flow velocity (MFV) of the left middle cerebral artery (MCA) was accelerated (57.33 (52.33-61.34) vs. 51.33 (48.83-58.33), respectively; p = 0.038), and the post-treatment DHI score was reduced (18 (13-19) vs. 34 (21-45), respectively; p = 0.043). The post-treatment volume of the white matter lesions (WMLs) was also reduced (4.19 (2.96-7.25) vs. 6.06 (4.67-10.95), respectively; p = 0.050). There was no remarkable difference between the 2 groups either before or after treatment. Conclusion: The present study indicates that RIPC has potential beneficial effects on cerebral SVD by increasing the MFV of MCA, decreasing the DHI score as well as the volume of WMLs in patients with SVD.

Oxygen stable isotope of atmospheric water vapor is widely used to study the modern process of climate. Atmospheric water vapor samples were collected at Dlingha, northeast of Tibetan Plateau during the period from July 2005 to February 2006. The variation of G 18 O and the relationships between G 18 O and both the temperature and specific humidity are analyzed in this paper. Results show that the seasonal variation of G 18 O of atmospheric water vapor at Delingha is remarkable with higher G 18 O in summer and lower G 18 O in winter. The temporal variation of vapor G 18 O shows obvious fluctuations, with magnitude of over 37‰. The daily variation of the G 18 O is highly correlated with air temperature. The relationship between G 18 O and atmospheric water vapor content is complex. Study shows that G 18 O of atmospheric water vapor is positively correlated with specific humidity in winter in seasonal scale and inversely correlated with specific humidity in summer rainy period. The G 18 O values of atmospheric water vapor are lower than those of precipitation at Delingha, and the average difference is 10.7‰. Variations of G 18 O of atmospheric water vapor is also found to be affected by precipitation events, The model results show that the precipitation effect could have caused the vapor G 18 O in the raining season to lower by 7% in average in July and August. Delingha, G 18 O, atmospheric water vaporAtmospheric water vapor plays a key role in the precipitation events. Therefore, the isotopic composition of atmospheric water vapor has a direct effect upon that of precipitation [1] , Observation of stable isotope variations of atmospheric water vapor is of great significance to indicate the moisture origins of precipitation and moisture transport in the study area. This is because isotopic ratios of water are affected strongly by water evaporation conditions and condensation history in the history of air mass. Stable isotopes of atmospheric water vapor will be potentially used in the research of biogeochemistry circulation. Land ecosystem and climate system interact with each other by the energy balance between land surface and atmosphere, vapor exchange and biogeochemistry circulation. This can make an effect on concentration of greenhouse gas and aerosol, and subsequently will cause climate change [2] . Such research becomes the hot topic of geochemistry and environment. Roden et al. [3] made an investigation on the exchange of isotopes in carbohydrates with xylem sap water during conversion into cellulose and a biochemical fractionation associated with cellulose synthesis. They also discussed the relation between this process and isotopes of atmospheric water vapor. According to Yepez's work, the relative contributions of overstory and understory

Abstract. This study investigated daily δ 18 O variations of water vapour (δ 18 O v ) and precipitation (δ 18 O p ) simultaneously at Nagqu on the central Tibetan Plateau for the first time. Data show that the δ 18 O tendencies of water vapour coincide strongly with those of associated precipitation. The δ 18 O values of precipitation affect those of water vapour not only on the same day, but also for the following several days. In comparison, the δ 18 O values of local water vapour may only partly contribute to those of precipitation. During the entire sampling period, the variations of δ 18 O v and δ 18 O p at Nagqu did not appear dependent on temperature, but did seem significantly dependent on the joint contributions of relative humidity, pressure, and precipitation amount. In addition, the δ 18 O changes in water vapour and precipitation can be used to diagnose different moisture sources, especially the influences of the Indian monsoon and convection. Moreover, intense activities of the Indian monsoon and convection may cause the relative enrichment of δ 18 O p relative to δ 18 O v at Nagqu (on the central Tibetan Plateau) to differ from that at other stations on the northern Tibetan Plateau. These results indicate that the effects of different moisture sources, including the Indian monsoon and convection currents, need be considered when attempting to interpret paleoclimatic records on the central Tibetan Plateau.