Regulation of cyp26a1 on Th17 cells in mouse peri‐implantation

Cytochrome P450 26A1 (cyp26a1) is expressed in the mouse uterus during peri‐implantation. The repression of this protein is closely associated with a reduction in implantation sites, suggesting a specific role for cyp26a1 in pregnancy and prompting questions concerning how a metabolic enzyme can generate this distinct outcome. To explore the effective downstream targets of cyp26a1 and confirm if its role in peri‐implantation depends on its metabolic substrate RA (retinoic acid), we characterized the changes in the peripheral blood, spleen and uterine implantation sites using the cyp26a1 gene vaccine constructed before. Flow cytometry results showed a significant increase in CD4⁺RORγt⁺ Th17 cells in both the peripheral blood and spleen in the experimental group. The expression of RORγt and IL‐17 presented the Th17 cells reduction in uterus followed by the suppression of cyp26a1 expression. For greater certainty, cyp26a1 antibody blocking model and RNA interference model were constructed to determine the precise target immune cell group. High performance liquid chromatography results showed a significant increase in uterine at‐RA followed by the immunization of cyp26a1 gene vaccine. Both the ascertain by measuring RARα protein levels in peri‐implantation uterus after gene vaccine immunization and researches using the specific agonist and antagonist against RARα suggested that RARα may be the main RA receptor for signal transduction. These results provided more evidence for the signal messenger role of RA in cyp26a1 regulation from the other side. Here, we showed that the cyp26a1‐regulated Th17 cells are dependent on at‐RA signalling, which is delivered through RARα in mouse peri‐implantation.     

Alfalfa (Medicago sativa L.)/Maize (Zea mays L.) Intercropping Provides a Feasible Way to Improve Yield and Economic Incomes in Farming and Pastoral Areas of Northeast China

Given the growing challenges to food and eco-environmental security as well as sustainable development of animal husbandry in the farming and pastoral areas of northeast China, it is crucial to identify advantageous intercropping modes and some constraints limiting its popularization. In order to assess the performance of various intercropping modes of maize and alfalfa, a field experiment was conducted in a completely randomized block design with five treatments: maize monoculture in even rows, maize monoculture in alternating wide and narrow rows, alfalfa monoculture, maize intercropped with one row of alfalfa in wide rows and maize intercropped with two rows of alfalfa in wide rows. Results demonstrate that maize monoculture in alternating wide and narrow rows performed best for light transmission, grain yield and output value, compared to in even rows. When intercropped, maize intercropped with one row of alfalfa in wide rows was identified as the optimal strategy and the largely complementary ecological niches of alfalfa and maize were shown to account for the intercropping advantages, optimizing resource utilization and improving yield and economic incomes. These findings suggest that alfalfa/maize intercropping has obvious advantages over monoculture and is applicable to the farming and pastoral areas of northeast China.     

Selenium as an anti-oxidant and pro-oxidant in ryegrass

Selenium is an essential element for antioxidation reactions in human and animals. In order to study its biological role in higher plants, ryegrass (Lolium perenne) was cultivated in a soil without Se or amended with increasing dosages of H₂SeO₄ (0.1, 1.0, 10.0 and 30.0 mg Se kg⁻¹). Ryegrass was harvested twice and the yields were analyzed for antioxidative systems and growth parameters. Selenium exerted dual effects: At low concentrations it acted as an antioxidant, inhibiting lipid peroxidation, whereas at higher concentrations, it was a pro-oxidant, enhancing the accumulation of lipid peroxidation products. The antioxidative effect was associated with an increase in glutathione peroxidase (GSH-Px) activity, but not with superoxide dismutase (SOD) and αα-tocopherol, which was the only tocopherol detected. In the second yield, the diminished lipid peroxidation due to a proper Se addition coincided with promoted plant growth. The oxidative stress found at the Se addition level ≥ 10 mg kg⁻¹ resulted in drastic yield losses. This result indicates that the toxicity of Se can be attributed, in addition to metabolic disturbances, to its pro-oxidative effects. Neither the growth-promoting nor the toxic effect of Se could be explained by the changes in the total chlorophyll concentration. This revised version was published online in June 2006 with corrections to the Cover Date.     

Development of Skewed Functionality of HIV-1-Specific Cytotoxic CD8+ T Cells from Primary to Early Chronic Phase of HIV Infection

In recent years, the prevalence of HIV-1 infection has been rapidly increasing among men who have sex with men (MSM). However, it remains unknown how the host immune system responds to the infection in this population. We assessed the quantity of HIV-specific CD8⁺ T-cell responses by using Elispot assay and their functionalities by measuring 5 CD8⁺ T-cell evaluations (IL-2, MIP-1β, CD107a, TNF-α, IFN-γ) with flow cytometry assays among 18 primarily and 37 early chronically HIV-infected MSM. Our results demonstrated that subjects at early chronic phase developed HIV-specific CD8⁺ T-cell responses with higher magnitudes and more diversified functionalities in comparison with those at primary infection. However, populations with IL-2⁺ CD107a⁺ or in combination with other functionality failed to develop in parallel. The multifunctional but not monofunctional HIV-specific CD8⁺ T cells were associated with higher CD4⁺ T -cell counts and lower viral loads. These data revealed that prolonged infection from primary to early chronic infection could selectively increase the functionalities of HIV-specific CD8⁺ T cells in HIV-infected MSM population, the failure to develop IL-2 and cytotoxic functionalities in parallel may explain why the increased HIV-specific CD8⁺ T cells were unable to enhance the containment of HIV-1 replication at the early chronic stage.     

Structural modulation of gut microbiota during alleviation of type 2 diabetes with a Chinese herbal formula

The gut microbiota is hypothesized to have a critical role in metabolic diseases, including type 2 diabetes (T2D). A traditional Chinese herbal formula, Gegen Qinlian Decoction (GQD), can alleviate T2D. To find out whether GQD modulates the composition of the gut microbiota during T2D treatment, 187 T2D patients were randomly allocated to receive high (HD, n=44), moderate (MD, n=52), low dose GQD (LD, n=50) or the placebo (n=41) for 12 weeks in a double-blinded trial. Patients who received the HD or MD demonstrated significant reductions in adjusted mean changes from baseline of fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) compared with the placebo and LD groups. Pyrosequencing of the V3 regions of 16S rRNA genes revealed a dose-dependent deviation of gut microbiota in response to GQD treatment. This deviation occurred before significant improvement of T2D symptoms was observed. Redundancy analysis identified 47 GQD-enriched species level phylotypes, 17 of which were negatively correlated with FBG and 9 with HbA1c. Real-time quantitative PCR confirmed that GQD significantly enriched Faecalibacterium prausnitzii, which was negatively correlated with FBG, HbA1c and 2-h postprandial blood glucose levels and positively correlated with homeostasis model assessment of β-cell function. Therefore, these data indicate that structural changes of gut microbiota are induced by Chinese herbal formula GQD. Specifically, GQD treatment may enrich the amounts of beneficial bacteria, such as Faecalibacterium spp. In conclusion, changes in the gut microbiota are associated with the anti-diabetic effects of GQD.     

Characterization of Sr9h,a wheat stem rust resistance allele effective to Ug99

Key message

Wheat stem rust resistance gene SrWeb is an allele at the Sr9 locus that confers resistance to Ug99.

Abstract

Race TTKSK (Ug99) of Puccinia graminis f. sp. tritici, the causal fungus of stem rust, threatens global wheat production because of its broad virulence to current wheat cultivars. A recently identified Ug99 resistance gene from cultivar Webster, temporarily designated as SrWeb, mapped near the stem rust resistance gene locus Sr9. We determined that SrWeb is also present in Ug99 resistant cultivar Gabo 56 by comparative mapping and an allelism test. Analysis of resistance in a population segregating for both Sr9e and SrWeb demonstrated that SrWeb is an allele at the Sr9 locus, which subsequently was designated as Sr9h. Webster and Gabo 56 were susceptible to the Ug99-related race TTKSF+ from South Africa. Race TTKSF+ possesses unique virulence to uncharacterized Ug99 resistance in cultivar Matlabas. This result validated that resistance to Ug99 in Webster and Gabo 56 is conferred by the same gene: Sr9h. The emergence of pathogen virulence to several resistance genes that are effective to the original Ug99 race TTKSK, including Sr9h, suggests that resistance genes should be used in combinations in order to increase resistance durability.     

膜翅目精子结构研究新进展

根据观察,膜翅目昆虫精子由顶体,精核,中部,尾部四个主要部分构成。顶体具顶体丝,中部具轴丝,中部与精核间具线粒体衍生物。本文同时对膜翅目,分别隶属12个科,10个总科中的2个亚目昆虫精子的顶体、精核、线粒体衍生物、轴丝等结构的研究状况进行概括,并应用精子结构特征对上述类群的系统发育状况进行讨论。     

广东地区三种木本植物抗大气污染能力的比较

研究了工业污染区(佛山市小塘镇五星WX)和相对清洁区(广州华南植物园BG)生长的3种木本植物光叶山矾(Symplocos lancifolia)、银柴(Aporosa chinensis)和窿缘桉(Eucalyptus exserta)叶片对酸碱缓冲能力的差别。工业污染区3种植物的细胞液pH均比相对清洁区的低,光叶山矾与银柴对酸和碱的缓冲能力强于窿缘桉。用外源NaHSO3处理,植物叶片的光合放氧、Fv／Fm、Fv／Fo和ФPsⅡ都有不同程度的下降。其中,窿缘桉下降的幅度最大,说明其抗大气污染的能力不如光叶山矾和银柴,同时也证明了用缓冲能力作为一种评价植物抗污能力的指标具有一定的科学性。     

Targeting CDH17 Suppresses Tumor Progression in Gastric Cancer by Downregulating Wnt/β-Catenin Signaling

Purpose

Gastric cancer remains one of the leading causes of cancer death worldwide. Patients usually present late with local invasion or metastasis, for which there are no effective therapies available. Following previous studies that identified the adhesion molecule Cadherin-17(CDH17) as a potential marker for gastric carcinoma, we performed proof-of-principle studies to develop rational therapeutic approaches targeting CDH17 for treating this disease.

Methods

Immunohistochemistry was used to study the expression of CDH17 in 156 gastric carcinomas, and the relationship between survival and CDH17 expression was studied by multivariate analyses. The effect of RNA interference–mediated knockdown of CDH17 on proliferation of gastric carcinoma cell lines was examined in vitro and in vivo, as well as the effects on downstream signaling by immunoblotting.

Results

CDH17 was consistently up-regulated in human gastric cancers, and overall survival in patients with CDH17 upregulation was poorer than in those without expression of this gene (5 yrs overall survival rate 29.0% vs. 45.0%, P<0.01). Functional assays demonstrated that CDH17 knockdown inhibited cell proliferation, adhesion, migration, invasion, clonogenicity and induce G0/G1 arrest. In mice, shRNA-mediated CDH17 knockdown markedly inhibits tumor growth; intratumoral injection of CDH17 shRNAs results in significant antitumor effects on transplanted tumor models. The antitumor mechanisms underlying CDH17 inhibition involve inactivation of Wnt/β-catenin signaling.

Conclusion

Our results identify CDH17 as a biomarker of gastric carcinoma and attractive therapeutic target for this aggressive malignancy.