基于造血干细胞为靶细胞的基因治疗

在基因治疗中,造血干细胞因为具有自我更新及分化为各种血细胞系的能力而成为一种很有吸引力的靶细胞。将外源目的基因导入造血干细胞,以纠正或补偿因基因缺陷和异常引起的疾病,特别是血液疾病已取得重要进展,例如:腺苷脱氨酶缺陷病、血友病、地中海贫血症及镰状细胞性贫血症等。而慢病毒以其转染效率高,能够感染非分裂期细胞的特点成为转染造血干细胞的最适合载体,本文就造血干细胞的特性、载体的选择及临床应用和基因治疗的安全性等方面作一综述。     

Long‐term balanced fertilization increases the soil microbial functional diversity in a phosphorus‐limited paddy soil

The influence of long‐term chemical fertilization on soil microbial communities has been one of the frontier topics of agricultural and environmental sciences and is critical for linking soil microbial flora with soil functions. In this study, 16S rRNA gene pyrosequencing and a functional gene array, geochip 4.0, were used to investigate the shifts in microbial composition and functional gene structure in paddy soils with different fertilization treatments over a 22‐year period. These included a control without fertilizers; chemical nitrogen fertilizer (N); N and phosphate (NP); N and potassium (NK); and N, P and K (NPK). Based on 16S rRNA gene data, both species evenness and key genera were affected by P fertilization. Functional gene array‐based analysis revealed that long‐term fertilization significantly changed the overall microbial functional structures. Chemical fertilization significantly increased the diversity and abundance of most genes involved in C, N, P and S cycling, especially for the treatments NK and NPK. Significant correlations were found among functional gene structure and abundance, related soil enzymatic activities and rice yield, suggesting that a fertilizer‐induced shift in the microbial community may accelerate the nutrient turnover in soil, which in turn influenced rice growth. The effect of N fertilization on soil microbial functional genes was mitigated by the addition of P fertilizer in this P‐limited paddy soil, suggesting that balanced chemical fertilization is beneficial to the soil microbial community and its functions.     

Proteomic Analysis of Urine to Identify Breast Cancer Biomarker Candidates Using a Label-Free LC-MS/MS Approach

Introduction

Breast cancer is a complex heterogeneous disease and is a leading cause of death in women. Early diagnosis and monitoring progression of breast cancer are important for improving prognosis. The aim of this study was to identify protein biomarkers in urine for early screening detection and monitoring invasive breast cancer progression.

Method

We performed a comparative proteomic analysis using ion count relative quantification label free LC-MS/MS analysis of urine from breast cancer patients (n = 20) and healthy control women (n = 20).

Results

Unbiased label free LC-MS/MS-based proteomics was used to provide a profile of abundant proteins in the biological system of breast cancer patients. Data analysis revealed 59 urinary proteins that were significantly different in breast cancer patients compared to the normal control subjects (p<0.05, fold change >3). Thirty-six urinary proteins were exclusively found in specific breast cancer stages, with 24 increasing and 12 decreasing in their abundance. Amongst the 59 significant urinary proteins identified, a list of 13 novel up-regulated proteins were revealed that may be used to detect breast cancer. These include stage specific markers associated with pre-invasive breast cancer in the ductal carcinoma in-situ (DCIS) samples (Leucine LRC36, MAST4 and Uncharacterized protein CI131), early invasive breast cancer (DYH8, HBA, PEPA, uncharacterized protein C4orf14 (CD014), filaggrin and MMRN2) and metastatic breast cancer (AGRIN, NEGR1, FIBA and Keratin KIC10). Preliminary validation of 3 potential markers (ECM1, MAST4 and filaggrin) identified was performed in breast cancer cell lines by Western blotting. One potential marker MAST4 was further validated in human breast cancer tissues as well as individual human breast cancer urine samples with immunohistochemistry and Western blotting, respectively.

Conclusions

Our results indicate that urine is a useful non-invasive source of biomarkers and the profile patterns (biomarkers) identified, have potential for clinical use in the detection of BC. Validation with a larger independent cohort of patients is required in the following study.     

气候变化对我国华北地区冬小麦发育和产量的影响

验证作物模型在我国华北冬小麦主产区是否适应的基础上,采用作物模型与气候模式相结合的研究方法,定量化地模拟预测了未来100年气候变化对华北冬小麦生产的影响.结果表明,从2000～2004年,华北地区冬小麦产量的模拟值与实测值的变化趋势基本一致,且生育期和产量变化不大.未来100年内华北地区冬小麦的生长期可能会有所缩短,平均缩短8.4 d;产量也会有不同程度的下降,平均减产10.1％.适当采取应对措施可以有效降低冬小麦的减产趋势.     

The effects of immunosuppression on regulatory CD4(+)CD25(+) T cells: impact on immunosuppression selection in transplantation

During immune response and T-cell activation, both effector T cells and regulatory T(T(reg)) cells are activated and regulated simultaneously by both positive and negative pathways. CD4(+)CD25(+) T(reg) cells play a critical role in immune tolerance to self antigens as well as to allografts in some transplant settings. Effective immunosuppressive regimens significantly reduced the incidence of acute allograft rejection in patients following organ transplantation. However, the impact of immunosuppressive treatment on the potential induction of transplant tolerance has not been well determined. In this review we summarize the effects of immunosuppressive reagents on CD4(+)CD25(+) T(reg) cells in order to bring attention to this issue, which may affect the choice of immunosuppressive regimen in the clinical setting.     

人小肠三叶因子在糙皮侧耳中的整合、表达及检测

用原生质体法将含双 35S_AMV启动子及人小肠三叶因子 (hITF)cDNA的表达载体导入糙皮侧耳 (Pleurotusostreatus)中 ,原生质体转化子在含有除草剂的培养基上初步筛选 ,获得抗性菌株。通过PCR分析证明hITFcDNA已整合到侧耳基因组中。以hITF为抗原免疫家兔制备了抗血清 ,纯化后的IgG以直接型酶联免疫吸附检测 (ELISA)方法测定效价 ,并建立起hITF的竞争型酶联免疫吸附检测 (ELISA)方法 ,给出了标准工作曲线 ,以应用于大规模表达菌株的筛选确立。检测表明 ,hITF在侧耳新鲜菌丝体中分 3个表达量段 :10 0 0～ 12 5 0ng g、14 80～ 170 0ng g、最高达2 0 0 0～ 2 2 5 0ng g ,约占总可溶性蛋白的 0 7%～ 1 5 %。Western印迹进一步分析证明hITF在侧耳中的表达。     

Broadening the avenue of intersubgenomic heterosis in oilseed Brassica

Accumulated evidence has shown that each of the three basic Brassica genomes (A, B and C) has undergone profound changes in different species, and has led to the concept of the “subgenome”. Significant intersubgenomic heterosis was observed in hybrids between traditional Brassica napus and first generation lines of new type B. napus. The latter were produced by the partial introgression of subgenomic components from different species into B. napus. To increase the proportion of exotic subgenomic components and thus achieve stronger heterosis, lines of first generation new type B. napus were intercrossed with each other, and subjected to intensive marker-assisted selection to develop the second generation of new type B. napus. The second generation showed better agronomic traits and a higher proportion of introgression of subgenomic components than did the first generation. Compared with the commercial hybrid and the hybrids produced with the first generation new type B. napus, the novel hybrids showed stronger heterosis for seed yield during the 2 years of field trials. The extent of heterosis showed a significant positive correlation with the introgressed subgenomic components in the parental new type B. napus. To increase the content of the exotic subgenomic components further and to allow sustainable breeding of novel lines of new type B. napus, we initiated the development of a gene pool for new type B. napus that contained a substantial amount of genetic variation in the A^r and C^c genome. We discuss new approaches to broaden the avenue of intersubgenomic heterosis in oilseed Brassica.