TNF-α induces upregulation of EGFR expression and signaling in human colonic myofibroblasts

The myofibroblast has recently been identified as an important mediator of tumor necrosis factor-α (TNF-α)-associated colitis and cancer, but the mechanism(s) involved remains incompletely understood. Recent evidence suggests that TNF-α is a central regulator of multiple inflammatory signaling cascades. One important target of TNF-α may be the signaling pathway downstream of the epidermal growth factor receptor (EGFR), which has been associated with many human cancers. Here, we show that long-term exposure of 18Co cells, a model of human colonic myofibroblasts, with TNF-α led to a striking increase in cell surface EGFR expression, an effect that was completely inhibited by cycloheximide. Subsequent EGFR binding by EGF and heparin binding (HB)-EGF was associated with enhanced EGFR tyrosine kinase activity, prolonged ERK activation, and a significant increase in cyclooxygenase-2 (COX-2) expression compared with 18Co cells treated with EGF and HB-EGF alone. TNF-α also increased EGFR expression and signaling in primary myofibroblasts isolated from human colon tissue. TNF-α-induced upregulation of EGFR may be a plausible mechanism to explain the exaggerated cellular responsiveness that characterizes inflammatory bowel disease and that may contribute to a microenvironment that predisposes to colitis-associated cancer through enhanced COX-2 expression.     

Intrinsically altered lung‐resident γδT cells control lung melanoma by producing interleukin‐17A in the elderly

Cancer is an age‐associated disease, potentially related to the altered immune system of elderly individuals. However, cancer has gradually decreased incidence in the eldest globally such as the most common lung cancer, the mechanisms of which remain to be elucidated. In this study, it was found that the number of lung‐resident γδT cells was significantly increased with altered gene expression in aged mice (20–24 months) versus young mice (10–16 weeks). Aged lung Vγ4⁺ and Vγ6⁺ γδT cells predominantly produced interleukin‐17A (IL‐17A), resulting in increased levels in the serum and lungs. Moreover, the aged mice exhibited smaller tumors and reduced numbers of tumor foci in the lungs after challenge with intravenous injection of B16/F10 melanoma cells compared with the young mice. Aged lung Vγ4⁺ and Vγ6⁺ γδT cells were highly cytotoxic to B16/F10 melanoma cells with higher expression levels of CD103. The markedly longer survival of the challenged aged mice was dependent on γδT17 cells, since neutralization of IL‐17A or depletion of indicated γδT cells significantly shortened the survival time. Consistently, supplementation of IL‐17A significantly enhanced the survival time of young mice with lung melanoma. Furthermore, the anti‐tumor activity of aged lung γδT17 cells was not affected by alterations in the load and composition of commensal microbiota, as demonstrated through co‐housing of the aged and young mice. Intrinsically altered lung γδT17 cells underlying age‐dependent changes control lung melanoma, which will help to better understand the lung cancer progression in the elderly and the potential use of γδT17 cells in anti‐tumor immunotherapy.     

Cloning, sequencing and function ofsanA, a gene involved in nikkomycin biosynthesis ofStreptomyces ansochromogenes

Several genetically stable mutants blocked in nikkomycin biosynthesis were obtained after the slightly germinated spores of Streptomyces ansochromogenes, a nikkomycin producer, were treated with ultra violet radiation. One of the mutants is the same in morpholotical differentiation as the wild type strain and is designated as NBB19. A DMA library was constructed using plasmid plJ702 as cloning vector, NBB19 as cloning recipient. A 6 kb DNA fragment which can genetically complement NBB19 was cloned when screening the library for antifungal activity. Sequence analysis showed that the 3 kb Bgl II-Sal I fragment contains one complete ORF (ORF1) and one partial ORF (ORF2). ORF1 is designated as sanA. sanA is 1 365 bp, encoding a protein consisting of 454 amino acid residues. Database searching indicated that sanA is homologous to the hypothetical methyltransferase in Pyrococcus horikoshli with 25% identities and 41% positives. Disruptant of sanA lost the ability to synthesize nikkomycin. It indicated that sa     

高原世居藏族α、β珠蛋白编码基因的克隆与测序

目的:通过对高原世居藏族α、β珠蛋白编码基因的分析,探讨藏族Hb高氧亲合力的分子机制.方法:高原现场采集健康成年男性藏族人骨髓样品,提取总RNA,通过逆转录聚合酶链反应(RT-PCR)获得人α和β珠蛋白的cDNA,与PGEM-T Easy质粒连接后,将α和β珠蛋白的cDNA转化JM109大肠杆菌中扩增培养,经酶切鉴定后测序,结果与NCBI数据库进行同源性比较.结果:藏族人α珠蛋白的cDNA与NCBI数据库登录的人cDNA序列相同,没有突变位点.一例藏族人β珠蛋白143位密码子发生了氧亲和力增高的碱基突变(CAC-＞CGC),其对应的氨基酸由His变为Arg(即Hb Abruzzo).结论:藏族人高氧亲和力变种的发现,为今后高原低氧适应相关基因的研究提供了线索.     

碳酸酐酶靶向性抑制剂甲苯磺烷唑胺对机体缺氧耐力的影响

目的:探讨甲苯磺烷唑胺对提高小鼠缺氧耐力的影响及其机制.方法:将健康昆明小鼠放入缺氧装置瓶中,测定密闭缺氧存活时间;将雄性昆明小鼠放入梯形笼中,置于小动物低压舱进行减压低氧,测定小鼠减压低氧存活时间;观察小鼠组织碳酸酐酶Ⅱ(CAⅡ)活性改变.采用预防给药方式,研究碳酸酐酶靶向性抑制剂甲苯磺烷唑胺对提高低氧耐力的作用.结...     

Marker-assisted breeding of a photoperiod-sensitive male sterile <Emphasis Type="Italic">japonica</Emphasis> rice with high cross-compatibility with <Emphasis Type="Italic">indica</Emphasis> rice

The incomplete fertility of japonica × indica rice hybrids has inhibited breeders’ access to the substantial heterotic potential of these hybrids. As hybrid sterility is caused by an allelic interaction at a small number of loci, it is possible to overcome it by simple introgression at the major sterility loci. Here we report the use of marker-assisted backcrossing to transfer into the elite japonica cv. Zhendao88 a photoperiod-sensitive male sterility gene from cv. Lunhui422S (indica) and the yellow leaf gene from line Yellow249 (indica). The microsatellite markers RM276, RM455, RM141 and RM185 were used to tag the fertility genes S5, S8, S7 and S9, respectively. Line 509S is a true-breeding photoperiod-sensitive male sterile plant, which morphologically closely resembles the japonica type. Genotypic analysis showed that the genome of line 509S comprises about 92% japonica DNA. Nevertheless, hybrids between line 509S and japonica varieties suffer from a level of hybrid sterility, although the line is highly cross-compatible with indica types, with the resulting hybrids expressing a significant degree of heterosis. Together, these results suggest that segment substitution on fertility loci based on known information and marker-assisted selection are an effective approach for utilizing the heterosis of rice inter-subspecies.     

Impaired thymic export and apoptosis contribute to regulatory T-cell defects in patients with chronic heart failure

Objective

Animal studies suggest that regulatory T (T_reg) cells play a beneficial role in ventricular remodeling and our previous data have demonstrated defects of T_reg cells in patients with chronic heart failure (CHF). However, the mechanisms behind T_reg-cell defects remained unknown. We here sought to elucidate the mechanism of T_reg-cell defects in CHF patients.

Methods and Results

We performed flow cytometry analysis and demonstrated reduced numbers of peripheral blood CD4⁺CD25⁺FOXP3⁺CD45RO⁻CD45RA⁺ naïve T_reg (nT_reg) cells and CD4⁺CD25⁺FOXP3⁺CD45RO⁺CD45RA⁻ memory T_reg (mT_reg) cells in CHF patients as compared with non-CHF controls. Moreover, the nT_reg/mT_reg ratio (p<0.01), CD4⁺CD25⁺FOXP3⁺CD45RO⁻ CD45RA⁺CD31⁺ recent thymic emigrant T_reg cell (RTE-T_reg) frequency (p<0.01), and T-cell receptor excision circle levels in T_reg cells (p<0.01) were lower in CHF patients than in non-CHF controls. Combined annexin-V and 7-AAD staining showed that peripheral T_reg cells from CHF patients exhibited increased spontaneous apoptosis and were more prone to interleukin (IL)-2 deprivation- and CD95 ligand-mediated apoptosis than those from non-CHF individuals. Furthermore, analyses by both flow cytometry and real-time polymerase chain reaction showed that T_reg-cell frequency in the mediastinal lymph nodes or Foxp3 expression in hearts of CHF patients was no higher than that of the non-CHF controls.

Conclusion

Our data suggested that the T_reg-cell defects of CHF patients were likely caused by decreased thymic output of nascent T_reg cells and increased susceptibility to apoptosis in the periphery.     

Feeding habitats of blue sheep (Pseudois nayaur) during winter and spring in Helan Mountains, China

The feeding habitat selection of blue sheep (Pseudois nayaur) was studied by direct observation method in the Helan Mountains, China during winter (from November to December) and spring (from April to June) from 2003 to 2004. We established 25 line transects to collect information on feeding habitats used by blue sheep. Blue sheep in the study area preferred mountain savanna forests, a habitat dominated by Ulmus glaucescens, with medium tree density (<4 individuals / 400 m²), moderate tree height (4–6 m), higher shrub density (> 5 individuals / 100 m²), higher shrub (> 1.3 m), higher food abundance (> 50 g), moderate distance to human disturbance (< 500 m), and mild distance to bare rock (< 2 m). Such habitats characterized by 12 ecological factors were preferred as feeding areas by blue sheep during winter. Similar to habitat selection by the species during winter, blue sheep also showed a preference for mountain savanna with tree dominated by Ulmus glaucescens and medium tree density (< 4 individuals / 400 m²) during spring. Nevertheless, blue sheep preferred medium tree height (< 6 m), moderate tree density (5–10 individuals / 100 m²), medium shrub height (1.3–1.7 m), higher food abundance (> 100 g), moderate altitude (< 2 000 m), moderate distance to water resource (< 500 m), and medium hiding cover (50%–75%) during spring. Selection of the feeding habitats by sheep showed a significant difference in vegetation type, landform feature, dominant tree, tree height, shrub density, distance to the nearest shrub, food abundance, slope direction, slope degree, distance to water resource, and hiding cover between winter and spring. Results of principal components analysis indicated that the first principal component accounted for 24.493% of the total variance among feeding habitat variance during winter, with higher loadings for vegetation type, dominant tree, tree height, distance to the nearest tree, shrub density, shrub height, altitude, distance to water resource, and distance to human disturbance. In spring, the first principal components explained 28.777% of the variance, with higher loadings for vegetation type, distance to the nearest tree, shrub height, distance to the nearest shrub, food abundance, altitude, and distance to human disturbance. Translated from Zoological Research, 2005, 26(6): 580–589 [译自: 动物学研究]     

植物激素相关核酸和蛋白质二级数据库的构建与应用

以NCBI维护的一级数据库为数据源建立植物激素相关核酸和蛋白质二级数据库。将该二级数据库设计为基因、蛋白质和文献三部分, 编写软件从上述数据源中采集数据, 并以XML作为中间格式保存, 通过解析提交到二级数据库中并集成部分生物信息学工具软件, 初步实现了数据检索、统计分析、基于Web的本地化BLAST同源序列检索、序列的自动拼接以及蛋白质结构和功能位点的分析等功能。该二级数据库的构建为植物激素作用分子机理研究提供了高针对性的植物激素数据源和生物信息学辅助工具。