Non-invasive estimation of root zone soil moisture from coarse root reflections in ground-penetrating radar images

Plant and Soil - Root zone soil moisture is an important component in water cycling through the soil-plant-atmosphere continuum. However, its measurement in the field remains a challenge,...     

Crystal structures of interleukin-2 tyrosine kinase and their implications for the design of selective inhibitors

Interleukin-2 tyrosine kinase, Itk, is an important member of the Tec family of non-receptor tyrosine kinases that play a central role in signaling through antigen receptors such as the T-cell receptor, B-cell receptor, and Fcepsilon. Selective inhibition of Itk may be an important way of modulating many diseases involving heightened or inappropriate activation of the immune system. In addition to an unliganded nonphophorylated Itk catalytic kinase domain, we determined the crystal structures of the phosphorylated and nonphosphorylated kinase domain bound to staurosporine, a potent broad-spectrum kinase inhibitor. These structures are useful for the design of novel, highly potent and selective Itk inhibitors and provide insight into the influence of inhibitor binding and phosphorylation on the conformation of Itk.     

Predominant allylic hydroxylation at carbons 6 and 7 of 4 and 5-ene functionalized steroids by the thermophilic fungus Rhizomucor tauricus IMI23312

This paper demonstrates for the first time transformation of a series of steroids (progesterone, androst-4-en-3,17-dione, testosterone, pregnenolone and dehydroepiandrosterone) by the thermophilic fungus Rhizomucor tauricus. All transformations were found to be oxidative (monohydroxylation and dihydroxylation) with allylic hydroxylation the predominant route of attack functionalizing the steroidal skeleta. Timed experiments demonstrated that dihydroxylation of progesterone, androst-4-en-3,17-dione and pregnenolone all initiated with hydroxylation on ring-B followed by attack on ring-C. Similar patterns of steroidal transformation to those observed with R. tauricus have been observed with some species of thermophilic Bacilli and mesophilic fungi. All metabolites were isolated by column chromatography and were identified by (1)H, (13)C NMR, DEPT analysis and other spectroscopic data. The application of thermophilic fungi to steroid transformation may represent a potentially rich source for the generation of new steroidal compounds as well as for uncovering inter and intraspecies similarities and differences in steroid metabolism.     

长江口外赤潮频发海区水文分布特征分析

对长江口外赤潮频发区的水文特征的分析表明,在这个海区,春,夏季由于长江入海径流量大,长江冲淡水在西南-东北向流的作用下发生转向;上升流一般发生在从第一个转向点到长江口外深槽顶端的西侧斜坡上,春季这个转向点偏北,夏季偏南,秋季因长江入海径流量小,似无转向点存在,春,夏季余流的分布特点是羽状锋区附近是表,底层流辐合区,涌升区的表层余流呈现辐散的特征,底层余流具有顺槽进入长江口或向长江口辐合的特征.     

The structural basis for high affinity binding of α1-acid glycoprotein to the potent antitumor compound UCN-01

The α1-acid glycoprotein (AGP) is an abundant blood plasma protein with important immunomodulatory functions coupled to endogenous and exogenous ligand-binding properties. Its affinity for many drug-like structures, however, means AGP can have a significant effect on the pharmokinetics and pharmacodynamics of numerous small molecule therapeutics. Staurosporine, and its hydroxylated forms UCN-01 and UCN-02, are kinase inhibitors that have been investigated at length as antitumour compounds. Despite their potency, these compounds display poor pharmokinetics due to binding to both AGP variants, AGP1 and AGP2. The recent renewed interest in UCN-01 as a cytostatic protective agent prompted us to solve the structure of the AGP2–UCN-01 complex by X-ray crystallography, revealing for the first time the precise binding mode of UCN-01. The solution NMR suggests AGP2 undergoes a significant conformational change upon ligand binding, but also that it uses a common set of sidechains with which it captures key groups of UCN-01 and other small molecule ligands. We anticipate that this structure and the supporting NMR data will facilitate rational redesign of small molecules that could evade AGP and therefore improve tissue distribution.     

Two steroidal saponins from Camassia cusickii induce L1210 cell death through the apoptotic mechanism.

Two steroidal saponins, tigogenin hexasaccharide-1 (TGHS-1, (25R)-5alpha-spirostan-3beta-yl 4-O-[2-0-[3-O-(alpha-L-rhamnopyranosyl)-beta-D-glucopyranosyl]-3-0-[4-0- (alpha-L-rhamnopyranosyl)-beta-D-glucopyranosyl]-beta-D-glucopyranosyl]-3-D- galactopyranoside) and tigogenin hexasaccharide-2 (TGHS-2, (25R)-5alpha-spirostan-3beta-yl 4-O-[2-0-[3-0-(beta-D-glucopyranosyl)-beta-D-glucopyranosyl]-3-0-[4-0- (alpha-L-rhamnopyranosyl)-beta-D-glucopyranosyl]-beta-D-glucopyranosyl]beta-D-galactopyranoside), were isolated from the fresh bulbs of Camassia cusickii. In murine leukemic L1210 cells, both compounds showed cytotoxicity with an EC50 value of 0.06 microM. The morphological observation revealed that TGHS-1 and TGHS-2 induced shrinkage in cell soma and chromatin condensation, suggesting apoptotic cell death. The cell death was confirmed to be apoptosis by Annexin V binding to phosphatidylserine in the cell membrane and excluding propidium iodide. A typical apoptotic DNA ladder and the cleavage of caspase-3 were observed after treatment with TGHS-1 and TGHS-2. In the presence of both the compounds, cells with sub-G1 DNA content were detected by flow cytometric analysis, indicating that TGHS-1 and TGHS-2 (each EC50 value of 0.1 microM) are the most powerful apoptotic saponins known. These results suggest that TGHS-1 and TGHS-2 induce apoptotic cell death through caspase-3 activation.     

Structural basis for the interaction of TAK1 kinase with its activating protein TAB1

Transforming growth factor-beta (TGF-beta)-activated kinase 1 (TAK1) is a member of the MAPKKK family of protein kinases, and is involved in intracellular signalling pathways stimulated by transforming growth factor beta, interleukin-1 and tumour necrosis factor-alpha. TAK1 is known to rely upon an additional protein, TAK1-binding protein 1 (TAB1), for complete activation. However, the molecular basis for this activation has yet to be elucidated. We have solved the crystal structure of a novel TAK1 chimeric protein and these data give insight into how TAK1 is activated by TAB1. Our results reveal a novel binding pocket on the TAK1 kinase domain whose shape complements that of a unique alpha-helix in the TAK1 binding domain of TAB1, providing the basis for an intimate hydrophobic association between the protein activator and its target.     

Fucoidan effectively provokes the innate immunity of white shrimp Litopenaeus vannamei and its resistance against experimental Vibrio alginolyticus infection

In this study, we examined the effect of fucoidan on the immune response of white shrimp Litopenaeus vannamei and its resistance against Vibrio alginolyticus infection. Fucoidan induced degranulation, caused changes in the cell morphology, and increased activation of prophenoloxidase (proPO) and the production of superoxide anions in vitro. Shrimp that received fucoidan via immersion at 100, 200, and 400 mg l^?1 after 3 h showed haemocyte proliferation and a higher mitotic index of haematopoietic tissue. In another experiment, the haemocyte count, phenoloxidase (PO) activity, and respiratory bursts (RBs) were examined after the shrimp had been fed diets containing fucoidan at 0 (control), 0.5, 1.0, and 2.0 g kg^?1 for 7–21 days. Results indicated that these parameters directly increased with time. The immune parameters of shrimp fed the 1.0 g kg^?1 diet were significantly higher than those of shrimp fed the 2.0 g kg^?1 diet after 14 and 21 days. Phagocytic activity and the clearance efficiency against V. alginolyticus were significantly higher in shrimp fed the 1.0 g kg^?1 diet compared to those of shrimp fed the 0, 0.5 and 2.0 g kg^?1 diets. In a separate experiment, shrimp that had been fed diets containing fucoidan for 21 days were challenged with V. alginolyticus at 10⁶ colony-forming units shrimp^?1. Survival rates of shrimp fed the 1.0 and 2.0 g kg^?1 diets were significantly higher than those of shrimp fed the 0 and 0.5 g kg^?1 diets for 96–120 h. We concluded that fucoidan provokes innate immunity of shrimp as evidenced by haemocyte degranulation, proPO activation, and the mitotic index of haematopoietic tissue, and that dietary administration of fucoidan at 1.0 g kg^?1 enhanced the immune response of shrimp and their resistance against V. alginolyticus infection.