河西走廊天然固沙植被区地表甲虫多样性及其对沙漠化的指示作用

干旱、半干旱区沙漠化强烈影响动植物分布及多样性,地表甲虫是荒漠中主要的动物类群,它们对沙漠化引起的植被和土壤环境变化响应十分敏感。鉴于此,以河西走廊中部张掖绿洲外围的天然固沙植被区作为研究区,依据沙漠化发育程度选择流动沙丘（ASD）、丘间低地（IL）、半固定（SFSD）和固定沙丘（FSD）4种生境,调查了地表甲虫群落组成及影响甲虫分布的植被和土壤环境。研究发现,4种生境地表甲虫群落组成明显不同并存在季节变异,5月ASD与IL、SFSD和FSD生境地表甲虫群落的相异性大于8月。5月和8月SFSD生境地表甲虫活动密度均显著高于其他生境,8月FSD生境地表甲虫多样性指数显著高于其他生境。不同大小甲虫对沙漠化的响应模式不同,大中型甲虫对沙漠化的响应较小型甲虫敏感,这在5月表现尤为明显。地表甲虫与环境因子的RDA分析结果表明,12个植被和土壤环境因子解释了49.8%的地表甲虫群落变异,其中植被环境解释了甲虫群落变异的16.3%,土壤环境解释了甲虫群落变异的4.2%,植被和土壤环境相互作用解释了甲虫群落变异的29.3%。pRDA分析结果表明,草本物种丰富度、灌木盖度、土壤有机碳含量和粗砂含量是影响地表甲虫分布的主要环境因子,它们解释了43.7%的地表甲虫群落变异。Pearson相关分析表明,草本物种丰富度与地表甲虫活动密度呈显著正相关,而与地表甲虫均匀度呈显著负相关;灌木盖度与地表甲虫多样性呈显著正相关;地表甲虫物种丰富度与灌木盖度和草本物种丰富度均呈显著正相关。此外,研究还发现戈壁琵甲、克氏扁漠甲、中华砚甲和甘肃齿足象可以用于指示FSD生境,东鳖甲属昆虫可以用于指数SFSD生境,谢氏宽漠王可以用于指示IL及ASD生境。     

Akt participation in the Wnt signaling pathway through Dishevelled

Inactivation of glycogen synthase kinase 3beta (GSK3beta) and the resulting stabilization of free beta-catenin are critical steps in the activation of Wnt target genes. While Akt regulates GSK3alpha/beta in the phosphatidylinositide 3-OH kinase signaling pathway, its role in Wnt signaling is unknown. Here we report that expression of Wnt or Dishevelled (Dvl) increased Akt activity. Activated Akt bound to the Axin-GSK3beta complex in the presence of Dvl, phosphorylated GSK3beta and increased free beta-catenin levels. Furthermore, in Wnt-overexpressing PC12 cells, dominant-negative Akt decreased free beta-catenin and derepressed nerve growth factor-induced differentiation. Therefore, Akt acts in association with Dvl as an important regulator of the Wnt signaling pathway.     

Synthesis of novel 2-nitroimidazole-tethered tricyclic quinolines, bearing a second heteroatom, and their in vitro evaluation as hypoxia-selective cytotoxins and radiosensitizers

Two novel nitroimidazole-based bioreductive compounds, 10-[3-(2-nitroimidazolyl)-propylamino]-3,4-dihydro-1H-thiopyrano[4,3-b]quinoline hydrochloride (8a) and 10-[3-(2-nitroimidazolyl)propylamino]-2-methyl-1,2,3,4-tetrahydro-benzo[b]-1,6-naphthyridine hydrochloride (8b) have been synthesized and evaluated in V79 cells as hypoxia-selective cytotoxins and radiosensitizers that target DNA through weak intercalation. Both compounds were relatively good radiosensitizers (C(1.6) values of 40.0+/-0.8 and 59.0+/-0.4 microM for 8a and 8b, respectively) but neither of the compounds was superior to 2 which does not carry a second heteroatom in the DNA-intercalating chromophore.     

Characterization and structure of a Zn2+ and [2Fe-2S]-containing copper chaperone from Archaeoglobus fulgidus

Bacterial CopZ proteins deliver copper to P1B-type Cu+-ATPases that are homologous to the human Wilson and Menkes disease proteins. The genome of the hyperthermophile Archaeoglobus fulgidus encodes a putative CopZ copper chaperone that contains an unusual cysteine-rich N-terminal domain of 130 amino acids in addition to a C-terminal copper binding domain with a conserved CXXC motif. The N-terminal domain (CopZ-NT) is homologous to proteins found only in extremophiles and is the only such protein that is fused to a copper chaperone. Surprisingly, optical, electron paramagnetic resonance, and x-ray absorption spectroscopic data indicate the presence of a [2Fe-2S] cluster in CopZ-NT. The intact CopZ protein binds two copper ions, one in each domain. The 1.8 A resolution crystal structure of CopZ-NT reveals that the [2Fe-2S] cluster is housed within a novel fold and that the protein also binds a zinc ion at a four-cysteine site. CopZ can deliver Cu+ to the A. fulgidus CopA N-terminal metal binding domain and is capable of reducing Cu2+ to Cu+. This unique fusion of a redox-active domain with a CXXC-containing copper chaperone domain is relevant to the evolution of copper homeostatic mechanisms and suggests new models for copper trafficking.     

Insulin increases H<Subscript>2</Subscript>O<Subscript>2</Subscript>-induced pancreatic beta cell death

Insulin resistance results, in part, from impaired insulin signaling in insulin target tissues. Consequently, increased levels of insulin are necessary to control plasma glucose levels. The effects of elevated insulin levels on pancreatic beta (β) cell function, however, are unclear. In this study, we investigated the possibility that insulin may influence survival of pancreatic β cells. Studies were conducted on RINm, RINm5F and Min-6 pancreatic β-cells. Cell death was induced by treatment with H₂O₂, and was estimated by measurements of LDH levels, viability assay (Cell-Titer Blue), propidium iodide staining and FACS analysis, and mitochondrial membrane potential (JC-1). In addition, levels of cleaved caspase-3 and caspase activity were determined. Treatment with H₂O₂ increased cell death; this effect was increased by simultaneous treatment of cells with insulin. Insulin treatment alone caused a slight increase in cell death. Inhibition of caspase-3 reduced the effect of insulin to increase H₂O₂-induced cell death. Insulin increased ROS production by pancreatic β cells and increased the effect of H₂O₂. These effects were increased by inhibition of IR signaling, indicative of an effect independent of the IR cascade. We conclude that elevated levels of insulin may act to exacerbate cell death induced by H₂O₂ and, perhaps, other inducers of apoptosis.     

Surprising negative association between IgG1 allotype disparity and anti-adalimumab formation: a cohort study

Introduction

The human monoclonal antibody adalimumab is known to induce an anti-globulin response in some adalimumab-treated patients. Antibodies against adalimumab (AAA) are associated with non-response to treatment. Immunoglobulins, such as adalimumab, carry allotypes which represent slight differences in the amino acid sequences of the constant chains of an IgG molecule. Immunoglobulins with particular IgG (Gm) allotypes are racially distributed and could be immunogenic for individuals who do not express these allotypes. Therefore, we investigated whether a mismatch in IgG allotypes between adalimumab and IgG in adalimumab-treated patients is associated with the development of AAA.

Methods

This cohort study consisted of 250 adalimumab-treated rheumatoid arthritis (RA) patients. IgG allotypes were determined for adalimumab and for all patients. Anti-idiotype antibodies against adalimumab were measured with a regular radio immunoassay (RIA), and a newly developed bridging enzyme linked immunosorbent assay (ELISA) was used to measure anti-allotype antibodies against adalimumab. The association between AAA and the G1m3 and the G1m17 allotypes was determined. For differences between groups we used the independent or paired samples t-test, Mann-Whitney test or Chi square/Fisher's exact test as appropriate. To investigate the influence of confounders on the presence or absence of AAA a multiple logistic regression-analysis was used.

Results

Adalimumab carries the G1m17 allotype. No anti-allotype antibodies against adalimumab were detected. Thirty-nine out of 249 patients had anti-idiotype antibodies against adalimumab (16%). IgG allotypes of RA patients were associated with the frequency of AAA: patients homozygous for G1m17 had the highest frequency of AAA (41%), patients homozygous for G1m3 the lowest frequency (10%), and heterozygous patients' AAA frequency was 14% (P = 0.0001).

Conclusions

An allotype mismatch between adalimumab and IgG in adalimumab-treated patients did not lead to a higher frequency of AAA. On the contrary, patients who carried the same IgG allotype as present on the adalimumab IgG molecule, had the highest frequency of anti-adalimumab antibodies compared to patients whose IgG allotype differed from adalimumab. This suggests that the allotype of adalimumab may not be highly immunogenic. Furthermore, patients carrying the G1m17-allotype might be more prone to antibody responses.     

Carbon–Temperature–Water change analysis for peanut production under climate change: a prototype for the AgMIP Coordinated Climate‐Crop Modeling Project (C3MP)

Climate change is projected to push the limits of cropping systems and has the potential to disrupt the agricultural sector from local to global scales. This article introduces the Coordinated Climate‐Crop Modeling Project (C3MP), an initiative of the Agricultural Model Intercomparison and Improvement Project (AgMIP) to engage a global network of crop modelers to explore the impacts of climate change via an investigation of crop responses to changes in carbon dioxide concentration ([CO₂]), temperature, and water. As a demonstration of the C3MP protocols and enabled analyses, we apply the Decision Support System for Agrotechnology Transfer (DSSAT) CROPGRO‐Peanut crop model for Henry County, Alabama, to evaluate responses to the range of plausible [CO₂], temperature changes, and precipitation changes projected by climate models out to the end of the 21st century. These sensitivity tests are used to derive crop model emulators that estimate changes in mean yield and the coefficient of variation for seasonal yields across a broad range of climate conditions, reproducing mean yields from sensitivity test simulations with deviations of ca. 2% for rain‐fed conditions. We apply these statistical emulators to investigate how peanuts respond to projections from various global climate models, time periods, and emissions scenarios, finding a robust projection of modest (<10%) median yield losses in the middle of the 21st century accelerating to more severe (>20%) losses and larger uncertainty at the end of the century under the more severe representative concentration pathway (RCP8.5). This projection is not substantially altered by the selection of the AgMERRA global gridded climate dataset rather than the local historical observations, differences between the Third and Fifth Coupled Model Intercomparison Project (CMIP3 and CMIP5), or the use of the delta method of climate impacts analysis rather than the C3MP impacts response surface and emulator approach.     

Cytokine-augmented culture of haematopoietic progenitor cells in a novel three-dimensional cell growth matrix

Studies aimed at the in vitro expansion of haematopoietic progenitor cells (HPCs) have suffered from the conflict of increasing cell numbers while maintaining long-term repopulating ability. We have developed a long-term bone marrow bioreactor culture system resembling the marrow-microenvironment that cultures HPCs in an inert, three-dimensional, porous biomatrix termed Cellfoam. Previous studies have shown that the short-term culture of CD34(+)cells in Cellfoam improved the maintenance and multipotency of haematopoietic stem cells compared to cells cultured on plastic dishes. In this study, we examined the effects of low concentrations of cytokines including stem cell factor (SCF), IL-3, and Flk-2/Flt-3 ligand, on the maintenance, preservation and multipotency of CD34(+) cells cultured for 3 or 6 weeks in Cellfoam. Analysis of cell yields using flow cytometry showed that in SCF and Flk-2/Flt-3 ligand-supplemented cultures as well as cytokine-free cultures, a higher number of CD45(+)34(+) and CD45(+)34(+)38(-) cells is observed in Cellfoam cultures as compared to plastic cultures. The function of cultured cells was evaluated in colony-forming assays. The data demonstrate that Cellfoam cultures supplemented with SCF and Flk-2/Flt-3 ligand resulted in a higher output of colony activity compared to plastic cultures. Analysis of CAFC (29 days) activity also demonstrated that primitive progenitors were maintained to a greater extent in Cellfoam cultures containing either no cytokines or low concentrations of early-acting cytokines. These data suggest that culture of HPCs in three-dimensional bioreactors such as Cellfoam for extended periods may benefit from the addition of low levels of early-acting cytokines, including SCF and Flk-2/Flt-3 ligand, resulting in high yields of cells that are enriched for multipotent haematopoietic progenitors. These findings demonstrate that a three-dimensional matrix promotes the survival of primitive HPCs in culture and may modulate the in vitro effects of cytokines.     

利手、优势足及扣手的遗传方式初探

采用Slater区分单基因和多基因遗传的计算模式及Smith无偏分析方法对21个家系资料的分析表明：利手、优势足、扣手特征均为常染色体单基因显性遗传,R型为显性性状。虽然环境因素对这类特征的表现也有一定的影响,但遗传因素仍起主要作用。 Abstract:The data of 21 families were analyzed by the method of Slater's calculating model to differentiate between single-gene and multi-gene heredity and by the method of non-deviation analysis.The results showed that the hereditary mode of handedness or preferential foot or hand-clasping is the dominant heredity of single gene of autosome,and the right type of all of them is the dominant character.In a way,although environmental factors affected the phenotypes of these characters,hereditary factors were also the decisive ones.     

利手、优势足及扣手的遗传方式初探

采用Slater区分单基因和多基因遗传的计算模式及Smith无偏分析方法对21个家系资料的分析表明：利手、优势足、扣手特征均为常染色体单基因显性遗传,R型为显性性状。虽然环境因素对这类特征的表现也有一定的影响,但影响因素仍起主要作用。