Anti-inflammatory inhibition of endothelial cell adhesion molecule expression by flavone derivatives

Endothelial expression of cell adhesion molecules (CAM) including VCAM-1, E-selectin, and PECAM-1 plays a leading role in atherosclerosis. Phenolic flavones have been shown to have an anti-inflammatory property. This study examines whether 3',4'-dimethoxy-7-hydroxyflavone (methoxyflavone) and 2',3',7-trihydroxyflavone (hydroxyflavone) inhibited monocyte adhesion to TNF-alpha-activated endothelium via reduction of CAM expression in human umbilical vein endothelial cells (HUVEC). In stimulated HUVEC the expression of VCAM-1 and E-selectin was enhanced with increasing mRNA levels. Methoxyflavone markedly interfered with the THP-1 monocyte adhesion to TNF-alpha-stimulated HUVEC. At concentrations of > or =25 microM, methoxyflavone blocked the induction of VCAM-1 but not that of E-selectin on the activated HUVEC. Immunocytochemical staining showed that methoxyflavone modestly inhibited PECAM-1 expression induced by TNF-alpha. In contrast, hydroxyflavone minimally inhibited TNF-alpha-stimulated E-selectin expression without affecting VCAM-1 level. The inhibitory effect of methoxyflavone on THP-1 adhesion to HUVEC appears to be greater than that of hydroxyflavone, most likely due to a greater inhibition of CAM expression. Thus, some flavone derivatives containing methoxy groups may have therapeutic potential attenuating inflammatory response-related atherosclerosis.     

Lowland rainforest avifauna and human disturbance: persistence of primary forest birds in selectively logged forests and mixed-rural habitats of southern Peninsular Malaysia

We compared the composition and structure of primary forest avifauna among primary forests, selectively logged forests and mixed-rural areas (e.g. villages and agricultural areas) of Peninsular Malaysia. We found that forests that were selectively logged at least 30 years ago contained only 73-75% of the 159 species of extant primary forest birds, with an increased proportion of dominant species. We estimated that only 28-32% of the primary forest species utilized the mixed-rural habitat, and that the number of species that bred in the agricultural landscapes might be even lower. The microhabitat of different species most affected their vulnerability to disturbance. Most small, arboreal frugivores and omnivores, and insectivores that fed from tree trunks, showed greater persistence in the mixed-rural habitat than ground dwelling bird species, which were affected most by disturbance. Resource abundance and variables that were closely related to forest disturbance such as the density of large trees, density of dead trees, canopy cover density and shrub volume influenced the distribution of the primary forest birds. Large primary forest reserves and a revision of short-cycle logging regimes (ca. 30 years) are needed if we are to conserve the lowland rainforest avifauna of Peninsular Malaysia and other parts of Southeast Asia.     

Lipoxygenase inhibitory activity of anacardic acids

6[8'(Z)-pentadecenyl]salicylic acid, otherwise known as anacardic acid (C15:1), inhibited the linoleic acid peroxidation catalyzed by soybean lipoxygenase-1 (EC 1.13.11.12, type 1) with an IC50 of 6.8 microM. The inhibition of the enzyme by anacardic acid (C15:1) is a slow and reversible reaction without residual activity. The inhibition kinetics analyzed by Dixon plots indicates that anacardic acid (C15:1) is a competitive inhibitor and the inhibition constant, KI, was obtained as 2.8 microM. Although anacardic acid (C15:1) inhibited the linoleic acid peroxidation without being oxidized, 6[8'(Z),11'(Z)-pentadecadienyl]salicylic acid, otherwise known as anacardic acid (C15:2), was dioxygenated at low concentrations as a substrate. In addition, anacardic acid (C15:2) was also found to exhibit time-dependent inhibition of lipoxygenase-1. The alk(en)yl side chain of anacardic acids is essential to elicit the inhibitory activity. However, the hydrophobic interaction alone is not enough because cardanol (C15:1), which possesses the same side chain as anacardic acid (C15:1), acted neither as a substrate nor as an inhibitor.     

The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling

The mammalian target of rapamycin (mTOR) protein kinase is a master growth promoter that nucleates two complexes, mTORC1 and mTORC2. Despite the diverse processes controlled by mTOR, few substrates are known. We defined the mTOR-regulated phosphoproteome by quantitative mass spectrometry and characterized the primary sequence motif specificity of mTOR using positional scanning peptide libraries. We found that the phosphorylation response to insulin is largely mTOR dependent and that mTOR exhibits a unique preference for proline, hydrophobic, and aromatic residues at the +1 position. The adaptor protein Grb10 was identified as an mTORC1 substrate that mediates the inhibition of phosphoinositide 3-kinase typical of cells lacking tuberous sclerosis complex 2 (TSC2), a tumor suppressor and negative regulator of mTORC1. Our work clarifies how mTORC1 inhibits growth factor signaling and opens new areas of investigation in mTOR biology.     

Two-dimensional nanosheets produced by liquid exfoliation of layered materials

If they could be easily exfoliated, layered materials would become a diverse source of two-dimensional crystals whose properties would be useful in applications ranging from electronics to energy storage. We show that layered compounds such as MoS(2), WS(2), MoSe(2), MoTe(2), TaSe(2), NbSe(2), NiTe(2), BN, and Bi(2)Te(3) can be efficiently dispersed in common solvents and can be deposited as individual flakes or formed into films. Electron microscopy strongly suggests that the material is exfoliated into individual layers. By blending this material with suspensions of other nanomaterials or polymer solutions, we can prepare hybrid dispersions or composites, which can be cast into films. We show that WS(2) and MoS(2) effectively reinforce polymers, whereas WS(2)/carbon nanotube hybrid films have high conductivity, leading to promising thermoelectric properties.     

基于图像处理技术的生物反应器浓度检测系统的开发

发酵过程生物参数的在线检测,是获得发酵过程生物信息的重要手段,也是进行合理最优控制的基础。但是,目前许多生物量只能离线检测,不能够为实时的控制系统利用。因此提出了基于图像处理技术的生物反应器浓度在线检测系统,系统由反应液循环与控制装置、反应液浓度光学检测装置、图像采集与处理装置、计算机以及相应的处理软件组成。通过与分光光度计的实验比较,证实了所设计的系统可以用于生物反应器浓度的在线测量,为实现发酵过程生物参数的在线检测提供了值得借鉴的设计思路和实现方法。     

Specific lipopolysaccharide found in cystic fibrosis airway Pseudomonas aeruginosa

Cystic fibrosis (CF) patients develop chronic airway infections with Pseudomonas aeruginosa (PA). Pseudomonas aeruginosa synthesized lipopolysaccharide (LPS) with a variety of penta- and hexa-acylated lipid A structures under different environmental conditions. CF patient PA synthesized LPS with specific lipid A structures indicating unique recognition of the CF airway environment. CF-specific lipid A forms containing palmitate and aminoarabinose were associated with resistance to cationic antimicrobial peptides and increased inflammatory responses, indicating that they are likely to be involved in airway disease.     

A magnetic nanoprobe technology for detecting molecular interactions in live cells

Technologies to assess the molecular targets of biomolecules in living cells are lacking. We have developed a technology called magnetism-based interaction capture (MAGIC) that identifies molecular targets on the basis of induced movement of superparamagnetic nanoparticles inside living cells. Efficient intracellular uptake of superparamagnetic nanoparticles (coated with a small molecule of interest) was mediated by a transducible fusogenic peptide. These nanoprobes captured the small molecule's labeled target protein and were translocated in a direction specified by the magnetic field. Use of MAGIC in genome-wide expression screening identified multiple protein targets of a drug. MAGIC was also used to monitor signal-dependent modification and multiple interactions of proteins.