Land use change in Asia and the ecological consequences

Viewed within a historical context, Asia has experienced dramatic land transformations, and currently more than 50% of Asian land area is under agriculture. The consequences of this transformation are manifold. Southeast Asia has the highest deforestation rate of any major tropical region. Many of the world’s large rivers and lakes in Asia have been heavily degraded. About 11 of 19 world megacities with more than 10 million inhabitants are in Asia. These land use activities have resulted in substantial negative ecological consequences, including increased anthropogenic CO₂ emissions, deteriorated air and water quality, alteration of regional climate, an increase of disease and a loss of biodiversity. Although land use occurs at the local level, it has the potential to cause ecological impact across local, regional and global scales. Reducing the negative environmental impacts of land use change while maintaining economic viability and social acceptability is an major challenge for most developing countries in Asia.     

牦牛ZP3基因的克隆及蛋白质结构的预测

本研究对牦牛ZP3基因的编码区进行了克隆,在此基础上对ZP3蛋白的分子结构预测,为研究牦牛受精生物学提供基础。根据GenBank中普通牛的ZP3核苷酸序列设计特异性引物,以牦牛卵巢组织总RNA为模板,通过RT-PCR技术扩增牦牛ZP3基因cDNA序列(GenBank登录号为GQ856646),利用DNAMAN生物软件进行核苷酸和氨基酸序列分析、蛋白质专家系统ExPASy进行ZP3蛋白质分子结构预测。结果表明,扩增出的牦牛ZP3基因编码序列长1 266 bp,编码421个氨基酸。牦牛与牛、猪、狗、人、鼠和鸡ZP3基因核苷酸相应序列的同源性分别为98.42%、96.73%、79.67%、78.71%、69.15%和56.61%,氨基酸同源性分别为98.10%、83.85%、74.24%、70.26%、62.62%和46.12%,符合物种进化规律。预测的ZP3蛋白二级和三级结构显示它是一个具有22个氨基酸信号肽的亲水性β-桶状跨膜蛋白。牦牛ZP3基因编码区的成功克隆,为进一步研究该基因的结构与功能及其在受精过程中的作用提供了基础。     

DHPC: a new tool to express genome structural features

The DHPC (DNA Hilbert-Peano curve) is a new tool for visualizing large-scale genome sequences by mapping sequences into a two-dimensional square. It utilizes the space-filling function of Hilbert-Peano mapping. By applying a Gauss smoothing technique and a user-defined color function, a large-scale genome sequence can be mapped into a two-dimensional color image. In the calculated DHPCs, many genome characteristics are revealed. In this article we introduce the method and show how DHPCs may be used to identify regions of different base composition. The power of the method is demonstrated by presenting multiple examples such as repeating sequences, degree of base bias, regions of homogeneity and their boundaries, and mark of annotated segments. We also present several genome curves generated by DHPC to demonstrate how DHPC can be used to find previously unidentified sequence features in these genomes.     

Design and identification of selective HER-2 sheddase inhibitors via P1' manipulation and unconventional P2' perturbations to induce a molecular metamorphosis

In an effort to obtain a MMP selective and potent inhibitor of HER-2 sheddase (ADAM-10), the P1' group of a novel class of (6S,7S)-7-[(hydroxyamino)carbonyl]-6-carboxamide-5-azaspiro[2.5]octane-5-carboxylates was attenuated and the structure-activity relationships (SAR) will be discussed. In addition, it was discovered that unconventional perturbation of the P2' moiety could confer MMP selectivity, which was hypothesized to be a manifestation of the P2' group effecting global conformational changes.     

Blockade of airway inflammation and hyperresponsiveness by HIV-TAT-dominant negative Ras

We have reported previously that HIV-TAT-dominant negative (dn) Ras inhibits eosinophil adhesion to ICAM-1 after activation by IL-5 and eotaxin. In this study, we evaluated the role of Ras in Ag-induced airway inflammation and hyperresponsiveness by i.p. administration into mice of dnRas, which was fused to an HIV-TAT protein transduction domain (TAT-dnRas). Uptake of TAT-dnRas (t(1/2) = 12 h) was demonstrated in leukocytes after i.p. administration. OVA-sensitization significantly increased eosinophil and lymphocyte numbers in bronchoalveolar lavage fluid 24 h after final challenge. Treatment of animals with 3-10 mg/kg TAT-dnRas blocked the migration of eosinophils from 464 +/- 91 x 10(3)/ml to 288 +/- 79 x 10(3)/ml with 3 mg/kg of TAT-dnRas (p < 0.05), and further decreased to 116 +/- 63 x 10(3)/ml after 10 mg/kg TAT-dnRas (p < 0.01). Histological examination demonstrated that inflammatory cell infiltration (largely eosinophils and mononuclear cells) and mucin production around the airways caused by OVA were blocked by TAT-dnRas. OVA challenge also caused airway hyperresponsiveness to methacholine, which was dose dependently blocked by treatment with TAT-dnRas. TAT-dnRas also blocked Ag-induced IL-4 and IL-5, but not IFN-gamma, production in lung tissue. Intranasal administration of IL-5 caused eosinophil migration into the airway lumen, which was attenuated by pretreatment with TAT-dnRas. By contrast, TAT-green fluorescent protein or dnRas lacking the TAT protein transduction domain did not block airway inflammation, cytokine production, or airway hyperresponsiveness. We conclude that Ras mediates Th2 cytokine production, airway inflammation, and airway hyperresponsiveness in immune-sensitized mice.     

Metalloprotease-mediated GH receptor proteolysis and GHBP shedding. Determination of extracellular domain stem region cleavage site

Growth hormone-binding protein (GHBP) is complexed to a substantial fraction of circulating GH. In humans, rabbits, and other species, GHBP derives from proteolytic shedding of the GH receptor (GHR) extracellular domain. In cell culture studies, stimuli such as phorbol ester, platelet-derived growth factor, or serum induce GHR proteolysis, which concomitantly yields shed GHBP in cell supernatants and a cell-associated cytoplasmic domain-containing GHR remnant. This process is sensitive to metalloprotease inhibition, and genetic reconstitution studies identify tumor necrosis factor-alpha converting enzyme (TACE/ADAM-17), a transmembrane metalloprotease, as a GHR sheddase. Stimuli that induce GHR proteolysis render cells less responsive to GH, but the mechanism(s) of this desensitization is not yet understood. In this study, we mapped the rabbit (rb) GHR cleavage site. We adenovirally expressed a C-terminal epitope-tagged rbGHR lacking most of its cytoplasmic domain, purified the remnant protein induced by the phorbol ester, PMA, and derived the cleavage site by N-terminal sequencing of the purified remnant. The N-terminal sequence, (239)FTCEEDFR(246), matched perfectly the rbGHR and suggests that cleavage occurs eight residues from the membrane in the proximal extracellular domain stem region. Deletion and alanine substitution mutagenesis indicated that, similar to other TACE substrates, the spacing of residues in this region, more than their identity, influences GHR cleavage susceptibility. Further, we determined that PMA pretreatment desensitized a cleavage-sensitive GHR mutant, but not a cleavage-insensitive mutant, to GH-induced JAK2 activation. These results suggest that inducible GHR proteolysis can regulate GH signaling.     

A truncated splice variant of KCNQ1 cloned from rat heart

KCNQ1 encodes a pore-forming subunit of potassium channels. Mutations in this gene cause inherited diseases, i.e., Romano-Ward syndrome and Jervell and Lange-Nielsen syndrome. A truncated isoform of KCNQ1 was reported to be expressed physiologically and to suppress a delayed rectifier potassium current dominant-negatively in human heart. However, it is not known whether this way of modulation occurs in other species. We cloned another truncated splice variant of KCNQ1 (tr-rKCNQ1) from rat heart. Judging from the deleted sequence of the tr-rKCNQ1, the genomic structure of rat in this portion might be different from those of human and mouse. Otherwise, an unknown exon might exist. RT-PCR analysis demonstrated that the tr-rKCNQ1 was expressed in fetal and neonatal hearts. When this gene was expressed along with a full-length KCNQ1, it suppressed potassium currents, whether a regulatory subunit minK was co-expressed or not.     

Synthesis of beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->6)]-beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->6)-[beta-D-Galp-(1-->4)-beta-D-Glcp-(1-->3)]-beta-D-GlcpOLauryl, an oligosaccharide with anti-tumor activity

A concise and effective synthesis of lauryl heptasaccharide 17 was achieved from the key intermediates lauryl 2,3,4,6-tetra-O-benzoyl-beta-D-galactopyranosyl-(1-->4)-2,3,6-tri-O-benzoyl-beta-D-glucopyranosyl-(1-->3)-2,4-di-O-benzoyl-beta-D-glucopyranoside (10) and isopropyl 2,4,6-tri-O-acetyl-3-O-allyl-beta-D-glucopyranosyl-(1-->3)-[2,3,4,6-tetra-O-benzoyl-beta-D-glucopyranosyl-(1-->6)]-2,4-di-O-acetyl-beta-D-glucopyranosyl-(1-->3)-2,4,6-tri-O-acetyl-1-thio-beta-D-glucopyranoside (15). The key trisaccharide glycosyl acceptor 10 was constructed by coupling 2,3,4,6-tetra-O-benzoyl-beta-D-galactopyranosyl-(1-->4)-2,3,6-tri-O-benzoyl-alpha-D-glucopyranosyl trichloroacetimidate (3) with lauryl 6-O-acetyl-2,4-di-O-benzoyl-beta-D-glucopyranoside (9), followed by deacetylation. The thioglycoside donor 15 was obtained by condensation of 2,4,6-tri-O-acetyl-3-O-allyl-beta-D-glucopyranosyl-(1-->3)-[2,3,4,6-tetra-O-benzoyl-beta-D-glucopyranosyl-(1-->6)]-2,4-di-O-acetyl-alpha-D-glucopyranosyl trichloroacetimidate (11) with isopropyl 4,6-O-benzylidene-1-thio-beta-D-glucopyranoside (12), followed by debenzylidenation and acetylation. A bioassay of the inhibition of S180 noumenal tumors showed that lauryl heptasaccharide 17 could be employed as a potential agent for cancer treatment.     

Adiponectin suppresses proliferation and superoxide generation and enhances eNOS activity in endothelial cells treated with oxidized LDL

Adiponectin (also known as 30-kDa adipocyte complement-related protein or Acrp30) is an abundant adipocyte-derived plasma protein with anti-atherosclerotic and insulin-sensitizing properties. In order to investigate the potential mechanism(s) of the vascular protective effect of adiponectin, we used cultured bovine endothelial cells (BAECs) to study the effect of recombinant globular adiponectin (gAd) on cellular proliferation and the generation of reactive oxygen species (ROS) induced by oxidized LDL (oxLDL). By RT-PCR, we found that BAECs preferentially express AdipoR1, the high-affinity receptor for gAd. Treatment of BAECs with oxLDL (10 μg/ml) for 16 h stimulated cell proliferation by ∼60%, which was inhibited by co-incubation with gAd. Cell treatment with gAd also inhibited basal and oxLDL-induced superoxide release, and suppressed the activation of p42/p44 MAP kinase by oxLDL. The effects of gAd were blocked by a specific polyclonal anti-adiponectin antibody (TJ414). OxLDL-induced BAEC proliferation and superoxide release were inhibited by the NAD(P)H oxidase inhibitor diphenyleneiodonium (DPI), but not the eNOS inhibitor l-nitroarginine methyl ester (l-NAME). Finally, gAd ameliorated the suppression of eNOS activity by oxLDL. These data indicate that gAd inhibits oxLDL-induced cell proliferation and suppresses cellular superoxide generation, possibly through an NAD(P)H oxidase-linked mechanism.     

Exploring the mechanism of competence development in Escherichia coli using quantum dots as fluorescent probes

The mechanism of divalent Ca2+ cation induction of Escherichia coli competence is still not fully understood, though it is a common method for introducing recombinant DNA into bacterial cells in gene engineering. Quantum dots (QDs), as a new fluorescent probe of being applied in biology research, have aroused great interest. In this paper, we explored the mechanism of E. coli competence development using QDs for the first time. Results showed that water-soluble QDs of diameter 3-4 nm could go into competent cells, but could not enter noncompetent cells. This result was further confirmed using atomic force microscopy and DNA transforming experiments, suggesting that nonphysiological, high concentrations of Ca2+ enhanced the penetrability of cell membranes so that QDs, which cannot enter cells normally due to their greater diameter (3-4 nm), can do so easily into competent cells. Therefore, we believe that, at least for E. coli, the mechanism of Ca2+-induced competence development is mediated physicochemically rather than physiologically.