闽三角城市群生态环境脆弱性及其驱动力

生态安全是地区社会经济可持续发展的基本前提之一,而生态环境脆弱性会威胁地区的生态安全,进行生态环境脆弱性评价具有重要意义。以闽三角城市群为例,分别选取2000年和2015年的高程、坡度、岩性、土壤类型、NDVI、年均降水量、年均温、人口密度、人均GDP、路网密度、景观多样性、土地利用程度和工业固体废弃物排放量等13个指标,基于空间主成分分析法,并结合全局Moran'I和LISA聚类图,从整体特征、空间差异、空间集聚、地类脆弱性分异以及驱动力5个方面,探讨闽三角城市群的生态环境脆弱性及其驱动力。结果表明:2000—2015年间,闽三角城市群的生态环境脆弱性整体处于中度脆弱,但呈现出由中度脆弱向重度脆弱过渡的趋势;2000—2015年间,生态环境脆弱性呈现出由东南沿海向西北内陆逐渐增强的整体趋势,并存在明显的地带性特征,东南沿海增长不明显,部分地区有所下降,而西北内陆增长明显;生态环境脆弱性存在显著的空间自相关性,且为显著正相关,在西北部山区地带为显著的高高聚集,在东南沿海平原地带为显著的低低聚集,16年间集聚性特征在空间上有所迁移和扩张;2000—2015年间,生态环境脆弱性在各地类存在着一定的异质性,其生态环境脆弱性指数大小顺序始终为:林地未利用地草地耕地水域建设用地,整体由中度脆弱向重度脆弱过渡;2000—2015年间,生态环境脆弱性的驱动力有所变化,但人口密度、景观多样性、岩性和土壤类型一直是闽三角城市群生态环境脆弱性主要的驱动力。     

Traction force-mediated B cell activation: how and why

<正>B and T lymphocytes are responsible for the acquisition of adaptive immune response, among which, B cells dominate humoral immunity. In vivo, B cells utilize surface expressed B cell receptors (BCRs) to sense antigens presented by antigen-presenting cells (APCs), and eventually mediate antibody response and immune memory. It is well recognized     

Effect of drought and ABA on growth, photosynthesis and antioxidant system of Cotinus coggygria seedlings under two different light conditions

We exposed seedlings of Cotinus coggygria var. cinerea to drought and exogenous abscisic acid (ABA) under two different light conditions. Two watering regimes (well-watered and drought), two exogenous ABA applications (no ABA and with ABA) and two light regimes (full sunlight and shade) were employed. Compared with well-watered treatment, drought treatment significantly reduced the relative growth rate, relative water content (RWC), net photosynthesis rate (A) and transpiration (E), but increased chlorophyll a (chla), carbon isotope (δ¹³C), endogenous ABA, malondialdehyde (MDA) and hydrogen peroxide (H₂O₂) contents, and guaiacol peroxidase (POD) and catalase (CAT) activities. There was an apparent alleviation of drought effects by shade, as indicated by the lower relative growth rate, and chlorophyll, MDA and H₂O₂ contents, and increases in indoleacetic acid (IAA) and reduced glutathione (GSH) contents. On the other hand, the exogenous ABA application under shade induced protective effects on drought-stressed seedlings, as visible in RWC, MDA, A, stomatal conductance (g_s), E, δ¹³C, ABA and IAA values. In all, our results suggest that seedlings of C. coggygria are more sensitive to drought under full-light than under shade.     

NeuA O-acetylesterase activity is specific for CMP-activated O-acetyl sialic acid in Streptococcus suis serotype 2

The two ubiquitously expressed sphingosine kinases (SphK) 1 and 2 are key regulators of the sphingolipid signaling pathway. Despite the formation of an identical messenger, i.e. sphingosine 1-phosphate (S1P), they exert strikingly different functions. Particularly, SphK2 is necessary for the phosphorylation of the sphingosine analog fingolimod (FTY720), which is protective in rodent stroke models. Using gene deficient mice lacking either SphK1 or SphK2, we investigated the role of the two lipid kinases in experimental stroke.We performed 2 h transient middle cerebral artery occlusion (tMCAO) and analyzed lesion size and neurological function after 24 h. Treatment groups received 1 mg/kg FTY720. Neutrophil infiltration, microglia activation, mRNA and protein expression of SphK1, SphK2 and the S1P₁ receptor after tMCAO were studied.Genetic deletion of SphK2 but not SphK1 increased ischemic lesion size and worsened neurological function after tMCAO. The protective effect of FTY720 was conserved in SphK1^−/− mice but not in SphK2^−/− mice.This suggests that SphK2 activity is an important endogenous protective mechanism in cerebral ischemia and corroborates that the protective effect of FTY720 is mediated via phospho-FTY720.     

An Integrated Approach to Uncover Driver Genes in Breast Cancer Methylation Genomes

Background

Cancer cells typically exhibit large-scale aberrant methylation of gene promoters. Some of the genes with promoter methylation alterations play “driver” roles in tumorigenesis, whereas others are only “passengers”.

Results

Based on the assumption that promoter methylation alteration of a driver gene may lead to expression alternation of a set of genes associated with cancer pathways, we developed a computational framework for integrating promoter methylation and gene expression data to identify driver methylation aberrations of cancer. Applying this approach to breast cancer data, we identified many novel cancer driver genes and found that some of the identified driver genes were subtype-specific for basal-like, luminal-A and HER2+ subtypes of breast cancer.

Conclusion

The proposed framework proved effective in identifying cancer driver genes from genome-wide gene methylation and expression data of cancer. These results may provide new molecular targets for potential targeted and selective epigenetic therapy.     

Effect of Mn toxicity on morphological and physiological changes in two <Emphasis Type="Italic">Populus cathayana</Emphasis> populations originating from different habitats

The cuttings of Populus cathayana were exposed to four different manganese (Mn) concentrations (0, 0.1, 0.5 and 1 mM) in a greenhouse to investigate the toxicity of Mn and the detoxifying responses of woody plants. Two contrasting populations of P. cathayana, which were from wet and dry climate regions in western China, respectively, were examined in our study. The results showed that high concentration of Mn caused significant decrease in shoot height, biomass accumulation, and leaf number and leaf areas. Injuries to the anatomical features of leaves were also found as the reduced thickness of palisade and spongy parenchyma, the decreased density in the conducting tissue and the collapse and split in the meristematic tissue in the central vein. Moreover, Mn treatments caused the accumulation of hydrogen peroxide (H₂O₂), and then resulted in oxidative stress indicated by the oxidation of proteins and DNA. Many physiological responses were employed to cope with the toxicity of Mn, including the increase in the contents of non-protein thiol (NP-SH), phytochelatins (PCs) and phenolics compounds and the stimulated activities of guaiacol peroxidase (GPX) and polyphenol oxidase (PPO) for the chelation of Mn and for the antioxidation of reactive oxygen species. The population from dry climate habitat showed a lower leaf concentration of Mn, higher contents of the chelators, and higher activities of GPX and PPO than did the wet climate population at the same Mn treatment, thereby possessing a superior Mn tolerance. In both populations, most of the Mn was accumulated in the shoot, which is favorable regarding phytoremediation.     

Diet-induced obesity accelerates oral carcinogenesis by recruitment and functional enhancement of myeloid-derived suppressor cells

Although obesity has been associated with an increased risk and aggressiveness of many types of carcinoma, whether it promotes squamous cell carcinoma remains unclear. To reveal the role of obesity in oral squamous cell carcinoma (OSCC) initiation and development, we used 4NQO-induced OSCC model mice to examine the impact of dietary obesity on carcinogenesis. The results showed that high-fat diet (HFD)-induced obesity significantly promoted the incidence of OSCC and altered the local immune microenvironment with the expansion of CD11b⁺Gr1⁺ myeloid-derived suppressor cells (MDSCs). The underlying mechanism that induced an immunosuppressive local microenvironment in obesity was the recruitment of MDSCs through the CCL9/CCR1 axis and enhancement of MDSC immunosuppressive function via intracellular fatty acid uptake. Furthermore, clinical samples verified the increase in infiltrated CD33⁺ (a marker of human MDSCs) cells in obese OSCC patients, and data from the TCGA dataset confirmed that CD33 expression was positively correlated with local adipocytes in OSCC. Survival analysis showed that enrichment of adipocytes and high expression of CD33 were associated with poor prognosis in OSCC patients. Strikingly, depletion of MDSCs significantly ameliorated HFD-promoted carcinogenesis in 4NQO-induced model mice. These findings indicate that obesity is also an important risk factor for OSCC, and cancer immunotherapy, especially targeting MDSCs, may exhibit greater antitumor efficacy in obese patients.Subject terms: Cancer microenvironment, Oral cancer     

Evolutionary diversification of Mesobuthus α-scorpion toxins affecting sodium channels

α-Scorpion toxins constitute a family of peptide modulators that induce a prolongation of the action potential of excitable cells by inhibiting voltage-gated sodium channel inactivation. Although they all adopt a conserved structural scaffold, the potency and phylogentic preference of these toxins largely vary, which render them an intriguing model for studying evolutionary diversification among family members. Here, we report molecular characterization of a new multigene family of α-toxins comprising 13 members (named MeuNaTxα-1 to MeuNaTxα-13) from the scorpion Mesobuthus eupeus. Of them, five native toxins (MeuNaTxα-1 to -5) were purified to homogeneity from the venom and the solution structure of MeuNaTxα-5 was solved by nuclear magnetic resonance. A systematic functional evaluation of MeuNaTxα-1, -2, -4, and -5 was conducted by two-electrode voltage-clamp recordings on seven cloned mammalian voltage-gated sodium channels (Na(v)1.2 to Na(v)1.8) and the insect counterpart DmNa(v)1 expressed in Xenopus oocytes. Results show that all these four peptides slow inactivation of DmNa(v)1 and are inactive on Na(v)1.8 at micromolar concentrations. However, they exhibit differential specificity for the other six channel isoforms (Na(v)1.2 to Na(v)1.7), in which MeuNaTxα-4 shows no activity on these isoforms and thus represents the first Mesobuthus-derived insect-selective α-toxin identified so far with a half maximal effective concentration of 130 ± 2 nm on DmNa(v)1 and a half maximal lethal dose of about 200 pmol g(-1) on the insect Musca domestica; MeuNaTxα-2 only affects Na(v)1.4; MeuNaTxα-1 and MeuNaTxα-5 have a wider range of channel spectrum, the former active on Na(v)1.2, Na(v)1.3, Na(v)1.6, and Na(v)1.7, whereas the latter acting on Na(v)1.3-Na(v)1.7. Remarkably, MeuNaTxα-4 and MeuNaTxα-5 are two nearly identical peptides differing by only one point mutation at site 50 (A50V) but exhibit rather different channel subtype selectivity, highlighting a switch role of this site in altering the target specificity. By the maximum likelihood models of codon substitution, we detected nine positively selected sites (PSSs) that could be involved in functional diversification of Mesobuthus α-toxins. The PSSs include site 50 and other seven sites located in functional surfaces of α-toxins. This work represents the first thorough investigation of evolutionary diversification of α-toxins derived from a specific scorpion lineage from the perspectives of sequence, structure, function, and evolution.     

Solution structure of BmKalphaIT01, an alpha-insect toxin from the venom of the Chinese scorpion Buthus martensii Karsch

The solution structure of an alpha-insect toxin from Buthus martensii Karsch, BmKalphaIT01, has been determined by two-dimensional NMR spectroscopy and molecular modeling techniques. Combining the sequence homology comparison and toxicity bioassays, BmKalphaIT01 has been suggested to be a natural mutant of alpha-insect toxins and so can serve as a tool to study the relationship of structure-function among this group of toxins. The overall structure of BmKalphaIT01 shares a common core structure consisting of an alpha-helix packed against a three-stranded antiparallel beta-sheet, which exhibits distinctive local conformations within the loops connecting these secondary structure elements. The solution structure of BmKalphaIT01 features a non-proline cis peptide bond between Asn9 and Tyr10, which is proposed to mediate the spatial closing of the five-residue turn (Gln8-Cys12) and the C-terminal segment (Arg58-His64) to form the NC domain and confer the toxin insect-specific bioactivity. Conformational heterogeneity is observed in the solution of BmKalphaIT01 and could be attributed to the cis-trans isomerization of the peptide bond between residues 9 and 10. The minor conformation of BmKalphaIT01 with a trans peptide bond between Asn9 and Tyr10 may be responsible for its moderate bioactivity against mammals. The cis-trans isomerization of the peptide bond between residues 9 and 10 may be the structural basis of dual pharmacological activities of alpha-insect and alpha-like scorpion toxins, which is supported by the fact that conformational heterogeneity occurs in the solution structures of LqhalphaIT, LqqIII, and LqhIII and by comparison of the solution structure of BmKalphaIT01 with those of some relevant alpha-type toxins.