An insulin analogue with gamma-amino butyric acid substitution for A13Leu-A14Tyr.

An insulin A chain analogue, [A13-14 GABA, A21 Ala]A chain, for which the dipeptide Leu-Try at A13-A14 was substituted by a non-coded amino acid, gamma-amino butyric acid (GABA) and A21 Asn by Ala, was prepared by stepwise Fmoc solid-phase manual synthesis and then combined with the natural B chain of porcine insulin to yield an insulin analogue, [A13-14 GABA, A21Ala] porcine insulin (GABA substituted insulin). This insulin analogue still retains 50% in vivo biological activity and 59% in receptor binding capacity. It can also be crystallized. These results indicate that its overall conformation is similar to the native form and that the side chains of A13Leu and A14Tyr are not essential for insulin activity. In addition, the replacement of a normal C-N peptide bond by an unnatural C-C bond may have general meaning in structure and function studies of other proteins.     

An Efficient Separator with Low Li‐Ion Diffusion Energy Barrier Resolving Feeble Conductivity for Practical Lithium–Sulfur Batteries

Due to unprecedented features including high‐energy density, low cost, and light weight, lithium–sulfur batteries have been proposed as a promising successor of lithium‐ion batteries. However, unresolved detrimental low Li‐ion transport rates in traditional carbon materials lead to large energy barrier in high sulfur loading batteries, which prevents the lithium–sulfur batteries from commercialization. In this report, to overcome the challenge of increasing both the cycling stability and areal capacity, a metallic oxide composite (NiCo₂O₄@rGO) is designed to enable a robust separator with low energy barrier for Li‐ion diffusion and simultaneously provide abundant active sites for the catalytic conversion of the polar polysulfides. With a high sulfur‐loading of 6 mg cm^?2 and low sulfur/electrolyte ratio of 10, the assembled batteries deliver an initial capacity of 5.04 mAh cm^?2 as well as capacity retention of 92% after 400 cycles. The metallic oxide composite NiCo₂O₄@rGO/PP separator with low Li‐ion diffusion energy barrier opens up the opportunity for lithium–sulfur batteries to achieve long‐cycle, cost‐effective operation toward wide applications in electric vehicles and electronic devices.     

Keratinocyte growth factor/fibroblast growth factor-7-regulated cell migration and invasion through activation of NF-kappaB transcription factors

Keratinocyte growth factor (KGF)/fibroblast growth factor-7 (FGF-7) is a paracrine- and epithelium-specific growth factor produced by cells of mesenchymal origin. It acts exclusively through FGF-7 receptor (FGFR2/IIIb), which is expressed predominantly by epithelial cells, but not by fibroblasts, suggesting that it might function as a paracrine mediator of mesenchymal-epithelial interactions. KGF/FGF-7 plays an essential role in the growth of epithelial cells and is frequently overexpressed in cancers of epithelial origin such as pancreatic cancer, switching paracrine stimulation of KGF/FGF-7 to an autocrine loop. Less is known, however, about the signaling pathways by which KGF/FGF-7 regulates the response of epithelial cells. To delineate the signaling pathways activated by KGF/FGF-7 and examine cellular response to KGF/FGF-7 stimulation, we performed functional analysis of KGF/FGF-7 action. In this report, we show that KGF/FGF-7 activated nuclear factor kappaB (NF-kappaB), which in turn induced expression of VEGF, MMP-9, and urokinase-type plasminogen activator and increased migration and invasion of KGF/FGF-7-stimulated human pancreatic ductal epithelial cells. Expression of phosphorylation-defective IkappaBalpha (IkappaBalphaS32A,S36A), which blocked NF-kappaB activation, inhibited KGF/FGF-7-induced gene expression and cell migration and invasion. Our results demonstrate for the first time that KGF/FGF-7 induces NF-kappaB activation and that NF-kappaB plays an essential role in regulation of KGF/FGF-7-inducible gene expression and KGF/FGF-7-initiated cellular responses. Thus, these findings identify one signaling pathway for KGF/FGF-7-regulated cell migration and invasion and suggest that paracrine sources of KGF/FGF-7 are one of the malignancy-contributing factors from tumor stroma.     

Formation of lymphocyte colonies under serum-free culture conditions in normal individuals and patients with chronic lymphocytic leukemia

This paper describes a culture system which supports the formation of B cell and some T cell colonies under serum-free conditions in peripheral blood samples of normal individuals and patients with chronic lymphocytic leukemia (CLL) of B cell type. In this system, serum is replaced by bovine serum albumin, transferrin, cholesterol, insulin and catalase or horseradish peroxidase. In addition, it is necessary to add staphylococcus protein A, mitomycin-treated T cells as feeders and phytohemagglutinin leukocyte-conditioned medium as a source of growth factors. The plating efficiency is greatly enhanced when normal cells are incubated with galactose oxidase prior to plating and when CLL cells are exposed sequentially to neuraminidase and galactose oxidase.     

M?ssbauer effect studies on some bioinorganic complexes of europium.

The bioinorganic complexes of europium with N-acetyl-DL-alanine, N-acetyl-DL-valine, and DL-alanyl-DL-alanine have been synthesized and the M?ssbauer spectra at room temperature have been measured for these solid state complexes. The M?ssbauer parameters indicate that the water molecules in these complexes are not directly linked to the central europium ion and are outside the coordination sphere of europium and biological ligands, and that the chemical bond between the europium ion and the ligands may be predominantly ionic in character, with the possibility of partial covalent contribution.     

Association of α-adducin and G-protein β3 genetic polymorphisms with hypertension: a meta-analysis of Chinese populations

Background

Mounting evidence has suggested that α-adducin and G-protein β3 (GNB3) genes are logical candidates for salt-sensitive hypertension. Some, but not all, studies have reported that α-adducin G460T and GNB3 C825T polymorphisms may influence the risk of the disease. To comprehensively address this issue, we performed a meta-analysis to evaluate the influence of these two polymorphisms on hypertension and potential biases in Chinese.

Methods

Data were analyzed using Stata (v11.0) and random-effects model was applied irrespective of between-studies heterogeneity, which was evaluated via subgroup and meta-regression analyses. Study quality was assessed in duplicate. Publication bias was weighed using Egger''s test and funnel plot.

Results

36 study populations totaling 9042 hypertensive patients and 8399 controls were finally identified. Overall, in allelic/genotypic/dominant/recessive models, no significant association was identified for both G460T and C825T polymorphisms (P>0.05) and there was possible heterogeneity (I ²>25%). Subgroup analyses by study design indicated that the magnitude of association in population-based studies was marginally significantly strengthened for α-adducin G460T allelic model (OR = 1.12; 95% CI: 1:00–1.25; P = 0.043). Moreover, subgroup analyses by geographic distribution indicated comparison of 825T with 825C yielded a marginally significant increased risk in southern Chinese only (OR = 1.48; 95% CI: 1.01–2.16; P = 0.045). Further meta-regression analyses showed that geographic regions were a significant source of between-study heterogeneity for both polymorphisms. There was a possibility of publication bias for G460T, but not for C825T.

Conclusions

Our overall results suggest null association of α-adducin G460T and GNB3 C825T polymorphisms with hypertension in Chinese but indicate local marginal significance of C825T, as a putative salt-sensitive switch, in southern Chinese.     

Arabidopsis DCP2, DCP1, and VARICOSE form a decapping complex required for postembryonic development

mRNA turnover in eukaryotes involves the removal of m7GDP from the 5' end. This decapping reaction is mediated by a protein complex well characterized in yeast and human but not in plants. The function of the decapping complex in the development of multicellular organisms is also poorly understood. Here, we show that Arabidopsis thaliana DCP2 can generate from capped mRNAs, m7GDP, and 5'-phosphorylated mRNAs in vitro and that this decapping activity requires an active Nudix domain. DCP2 interacts in vitro and in vivo with DCP1 and VARICOSE (VCS), an Arabidopsis homolog of human Hedls/Ge-1. Moreover, the interacting proteins stimulate DCP2 activity, suggesting that the three proteins operate as a decapping complex. Consistent with their role in mRNA decay, DCP1, DCP2, and VCS colocalize in cytoplasmic foci, which are putative Arabidopsis processing bodies. Compared with the wild type, null mutants of DCP1, DCP2, and VCS accumulate capped mRNAs with a reduced degradation rate. These mutants also share a similar lethal phenotype at the seedling cotyledon stage, with disorganized veins, swollen root hairs, and altered epidermal cell morphology. We conclude that mRNA turnover mediated by the decapping complex is required for postembryonic development in Arabidopsis.     

生态环境脆弱带ECOTONE的基础判定

ECOTONE为国际生态界最近重新定义的基本概念之一。本文在诠释生态环境脆弱带的定义之后,对其实质及其空间属性作了较全面的逻辑归纳。在进一步研究的基础上,对于生态环境脆弱带作出了独立的函数表达,并且就生态环境脆弱带的宽度指标、重迭度指标、脆弱度指标、综合性指标,提出了较严格的表述形式。它们吸收了生态界面理论,并把系统生态学中的非稳定性理论,广延为辨识“全球变化”的基本手段,从而在生态学理论与应用两个方面,体现了研究的意义和价值。