Mining the cinnabaramide biosynthetic pathway to generate novel proteasome inhibitors

The cinnabaramides and salinosporamides are mixed PKS/NRPS natural products isolated from a terrestrial streptomycete and a marine actinomycete, respectively. They interfere with the proteasome and thus potentially inhibit the growth of cancer cells. The compounds exhibit a γ-lactam-β-lactone bicyclic ring structure attached to a cyclohexenyl unit and a PKS side chain. As a first step towards improving anticancer activity and permitting genetic approaches to novel analogues, we have cloned and characterized the cinnabaramide biosynthetic genes from Streptomyces sp. JS360. In addition to the expected PKS and NRPS genes, the cluster encodes functionalities for the assembly of the hexyl side chain precursor. The corresponding enzymes exhibit relaxed substrate specificities towards a number of synthesized precursors, enabling production of novel chlorinated cinnabaramides. These were isolated and analyzed for activity, revealing that derivatives bearing a chlorine atom in the PKS side chain show higher inhibitory potentials towards the proteasome's proteolytic subunits (especially the trypsin and chymotrypsin units) and higher cytotoxicities towards human tumor cell lines than the parent cinnabaramide A. Although their activities towards the proteasome were weaker than that of salinosporamide A, the cinnabaramides were found to inhibit the growth of various fungi with greater potency.     

Activity-based profiling of retaining β-glucosidases: a comparative study

Activity-based protein profiling (ABPP) is a versatile strategy to report on enzyme activity in vitro, in situ, and in vivo. The development and use of ABPP tools and techniques has met with considerable success in monitoring physiological processes involving esterases and proteases. Activity-based profiling of glycosidases, on the other hand, has proven more difficult, and to date no broad-spectrum glycosidase activity-based probes (ABPs) have been reported. In a comparative study, we investigated both 2-deoxy-2-fluoroglycosides and cyclitol epoxides for their utility as a starting point towards retaining β-glucosidase ABP. We also investigated the merits of direct labeling and two-step bio-orthogonal labeling in reporting on glucosidase activity under various conditions. Our results demonstrate that 1) in general cyclitol epoxides are the superior glucosidase ABPs, 2) that direct labeling is the more efficient approach but it hinges on the ability of the glucosidase to be accommodated in the active site of the reporter (BODIPY) entity, and 3) that two-step bio-orthogonal labeling can be achieved on isolated enzymes but translating this protocol to cell extracts requires more investigation.     

可记录DVD格式的在线生产控制

1引言:高级的可录DVD格式需要高级的测试设备 放眼当今市场,终端消费者已逐步接受可录DVD格式;展望不久的将来,可录DVD必将取代CD-R成为数据备份的标准存储媒体。因而盘片复制商、生产线制造商、测试设备提供商都越来越关注DVD-R。     

Combustion and emission characteristics of converging group-hole nozzle under lean engine operating conditions

This paper describes the combustion and emission characteristics of converging group-hole nozzles and compares the results to those of a single hole nozzle with the same overall nozzle exit hole area. Engine experiments were performed using a single-cylinder diesel engine operating under overall lean conditions (i.e., equivalence ratio 0.45). The considered nozzle configurations in the experiments included a converging group-hole nozzle (cGHN) with 3° converging angle, 0.090 mm hole diameter, and a single hole nozzle (SHN) of 0.128 mm hole diameter. The CFD calculations used the KIVA engine simulation code integrated with a Gasjet superposition model. Using the validated calculation models, the test conditions were also expanded to consider wider converging angle cGHNs (up to 12°). The results show that the evaporation of sprays from the cGHN-3° nozzle is more delayed than that of the SHN case and the cGHNs entrain more ambient gas due to smaller droplet sizes in the outer spray periphery. In addition, an increase in the converging angle of the cGHNs promotes fuel evaporation and produces a more homogeneous fuel–air mixture.     

The use of microwave irradiation for the easy synthesis of graphene-supported transition metal nanoparticles in ionic liquids

Stable ruthenium or rhodium metal nanoparticles were supported on chemically derived graphene (CDG) surfaces with small and uniform particle sizes (Ru 2.2 ± 0.4 nm and Rh 2.8 ± 0.5 nm) by decomposition of their metal carbonyl precursors by rapid microwave irradiation in a suspension of CDG in the ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate. The graphene-supported hybrid nanoparticles were shown to be active and could be re-used at least 10 times as catalysts for the hydrogenation of cyclohexene and benzene under organic-solvent-free conditions with constant activities up to 1570 mol cyclohexane × (mol metal)⁻¹ × h⁻¹ at 4 bar and 75 °C.     

Kinetics of Solid-State Reactions in Heterogeneous Catalysis from Time-Resolved X-Ray Absorption Spectroscopy

The potentials of X-ray absorption spectroscopy (XAS) (quantitative phase composition and average valence together with a short-range order structure analysis) combined with a time-resolution in the second range make time-resolved (TR-) XAS a powerful tool for investigating the reactivity of solids in catalysis and solid-state chemistry. General aspects of TR-XAS investigations are discussed (i.e., instrumentation, data analysis). In addition, some experiments illustrate how the kinetics of solid-state reactions in heterogeneous catalysis can be elucidated from TR-XAS studies.     

On the relationship between wavelength and perceived hue

Unlike in the case of sound where there is a compressed but straightforward relationship between frequency of sound waves and the perceived pitch, in the case of color the relationship is highly nonlinear, as first pointed out by Ostwald in 1916. In this article, the relationship between the perceptual Munsell hue scale and the related dominant wavelengths of the color chips involved is investigated. A hypothesis is proposed according to which the immediate cause of the nonlinearity can be found in the relative activation of the kinds of chromatically opponent functions shown to exist in neurons of the lateral geniculate nuclei. However, at this time, the relationship is only correlational, given the lack of deeper understanding of the relationship between the physiological operation of the color vision system and conscious experiences of color. © 2011 Wiley Periodicals, Inc. Col Res Appl, 2011;