Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing

Most patients with acute myeloid leukaemia (AML) die from progressive disease after relapse, which is associated with clonal evolution at the cytogenetic level. To determine the mutational spectrum associated with relapse, we sequenced the primary tumour and relapse genomes from eight AML patients, and validated hundreds of somatic mutations using deep sequencing; this allowed us to define clonality and clonal evolution patterns precisely at relapse. In addition to discovering novel, recurrently mutated genes (for example, WAC, SMC3, DIS3, DDX41 and DAXX) in AML, we also found two major clonal evolution patterns during AML relapse: (1) the founding clone in the primary tumour gained mutations and evolved into the relapse clone, or (2) a subclone of the founding clone survived initial therapy, gained additional mutations and expanded at relapse. In all cases, chemotherapy failed to eradicate the founding clone. The comparison of relapse-specific versus primary tumour mutations in all eight cases revealed an increase in transversions, probably due to DNA damage caused by cytotoxic chemotherapy. These data demonstrate that AML relapse is associated with the addition of new mutations and clonal evolution, which is shaped, in part, by the chemotherapy that the patients receive to establish and maintain remissions.     

Xenogeneic homologous genes, molecular evolution and cancer therapy

Cancer is one of the main causes for death of human beings to date, and cancer biotherapy (mainlyimmunotherapy and gene therapy) has become the most promising approach after surgical therapy, radiotherapy andchemotherapy. However, there are still many limitations on cancer immunotherapy and gene therapy; therefore great ef-fort is being made to develop new strategies. It has been known that, in the process of evolution, a number of genes, theso-called xenogeneic homologous genes, are well-conserved and show the structural and/or functional similarity betweenvarious species to some degree. The nucleotide changes between various xenogeneic homologous genes are derived frommutation, and most of them are neutral mutations. Considering that the subtle differences in xenogeneic homologousgenes can break immune tolerance, enhance the immunogenicity and induce autologous immune response so as to elimi-nate tumor cells, we expect that a strategy of inducing autoimmune response using the property of xenogeneic homologousgenes will become a new therapy for cancer. Moreover, this therapy can also be used in the treatment of other diseases,such as autoimmune diseases and AIDS. This article will discuss the xenogeneic homologous genes, molecular evolutionand cancer therapy.     

自适应量子交叉克隆选择算法

为克服传统克隆选择算法易于陷入局部最优的缺点,提出了自适应量子交叉免疫算法。自适应量子交叉算子在算法演化初期通过高适配度抗体对低适配度抗体的影响,加速收敛过程,而在算法演化后期,利用低适配度抗体对高适配度抗体的扰动,增加算法跳出局部最优的概率。对旅行商问题、单目标和多目标孔群加工路径优化问题所做的计算,结果表明:自适应量子克隆选择算法能有效平衡全局搜索和局部挖掘能力,在收敛速度和稳定性上优于同类克隆选择算法和其他启发式算法。     

一种用于多目标优化的克隆选择算法

多目标进化算法的研究目标是使算法种群快速收敛并均匀分布于问题的Pareto最优前沿面.为此,在比较与分析已有多目标进化算法的基础上,借鉴免疫系统中的克隆选择原理,提出了一种用于多目标优化的克隆选择算法.该方法只对部分当前所得到的Pareto最优解进行进化操作,并选用一种简单的多样性保护机制来保证Pareto最优解具有良好的分布特征.'实验结果表明该方法能够很好地达到Pareto最优前沿面,较好地保持解的多样性,并且具有很快的收敛速度.     

不夜城的快速繁殖

以不夜城幼茎为材料，经表面消毒后接种于诱导培养基上，4周左右出现不定芽不定芽在壮苗培养基上培养2周转至生根培养基上，又经3周长出完整根系，再生根株炼苗后移栽到基质中，移栽成活率为90％。     

苹果无性系品种的过氧化物酶同工酶酶谱分析

本试验将同工酶技术应用到果树品种间,尤其是无性系品种间差异分析中,证明在苹果无性系中,富士系与元帅系之间存在着较大的差别,而富士系与国光更为接近。另外,在富士系各品种间也存在着显著的差异。     

人工免疫中克隆选择算法的改进

在传统的基于免疫的克隆选择算法基础上加以改进，引入了再选择的机制，提出了多层次的动态克隆选择算法，对入侵检测的人工免疫模型进行了有效改进，使得对抗原的识别率更为有效．     

克隆植物的特性及研究进展

论述了克隆植物在繁殖与生存等方面的优势及其生态功能;综述了克隆植物的研究进展并分析了克隆植物研究的空白及发展方向。旨在推动我国克隆植物研究的深入开展。     

北冬虫夏草液体深层发酵最适营养的研究

通过摇瓶单因子和正交设计试验结果。液体培养的最佳营养条件为：葡萄糖２％，食用糖１％，酵母膏１％，蛋白胨１％，ＮＨ４Ｃｌ０．２％，ＭｇＳＯ４．７Ｈ２Ｏ０．０５％，ＫＣｌ１０．１％，１００立升发酵罐结果，碳，氮源分别为食用糖３％，蛋白胨１．５％。     

过路黄克隆生长对光照强度的反应

利用遮阳网产生光照梯度，以研究光照强度对克隆植物过路黄(Lysimachia christinae)形态特征和生物量分配的影响．结果表明：1)匍匐茎节间长度随光照强度的减弱而增大，遮荫明显增加过路黄的分枝角度，分枝强度没有对光强发生显著反应．遮荫使叶柄变长，而根长则变短．2)随光照强度的减弱，叶柄生物量逐渐增大；遮荫降低了叶生物量、根生物量、总生物量、根生物量比和地下生物量／地上生物量．3)在遮荫条件下，一级匍匐茎基部分株的叶生物量和分株总生物量显著大于顶部分株，而根冠比则相反．根的生物量在各分株间无显著差异．在不遮荫条件下，仅匍匐茎基部分株的叶生物量大于顶部分株，其它的生物量指标在各分株间无显著差异．在分株水平，分株的根冠比不受光强的影响．总之，过路黄的克隆生长在基株和分株水平都对光强作出了明显的反应，而且这种反应具有等级性．     

Clonal origin of haematopoietic colonies in the postnatal mouse liver

The liver of the neonatal mouse continues to show haematopoietic activity for up to 2 weeks after birth and morphological analysis has shown that this activity becomes focused in discrete haematopoietic colonies by the end of the first week postnatal. Furthermore, each colony contains cells of one haematopoietic lineage only, that is, erythroid, myeloid or pre-B-lymphoid cells. This pattern of differentiation suggests that each colony is derived from a single committed precursor cell, which, if true, would represent the first demonstration of non-mixed haematopoietic colonies in normal development and would provide a useful system for studying the factors affecting the clonal diversity of haematopoietic stem cells and their lineage-committed progeny. Here we have analysed the haematopoietic foci in the liver of neonatal mouse chimaeras, using a newly developed ubiquitous in situ cell marker system which clearly demonstrates the clonal origin of these colonies.     

Distant metastasis occurs late during the genetic evolution of pancreatic cancer

Metastasis, the dissemination and growth of neoplastic cells in an organ distinct from that in which they originated, is the most common cause of death in cancer patients. This is particularly true for pancreatic cancers, where most patients are diagnosed with metastatic disease and few show a sustained response to chemotherapy or radiation therapy. Whether the dismal prognosis of patients with pancreatic cancer compared to patients with other types of cancer is a result of late diagnosis or early dissemination of disease to distant organs is not known. Here we rely on data generated by sequencing the genomes of seven pancreatic cancer metastases to evaluate the clonal relationships among primary and metastatic cancers. We find that clonal populations that give rise to distant metastases are represented within the primary carcinoma, but these clones are genetically evolved from the original parental, non-metastatic clone. Thus, genetic heterogeneity of metastases reflects that within the primary carcinoma. A quantitative analysis of the timing of the genetic evolution of pancreatic cancer was performed, indicating at least a decade between the occurrence of the initiating mutation and the birth of the parental, non-metastatic founder cell. At least five more years are required for the acquisition of metastatic ability and patients die an average of two years thereafter. These data provide novel insights into the genetic features underlying pancreatic cancer progression and define a broad time window of opportunity for early detection to prevent deaths from metastatic disease.     

混沌云克隆选择算法及其应用

结合云模型理论与免疫克隆选择思想,提出一种新的改进算法-混沌云克隆选择算法(CCCSA).该算法采用混沌初始化生成初始种群以提高初始抗体的质量;通过基本正态云发生器实现抗体的变异操作以改善抗体的多样性.经典函数测试实验和时滞系统的自抗扰控制器参数优化整定仿真实验结果表明,该算法比一般的CSA算法、遗传算法和粒子群算法能更快的找到最优解;其求解精度更高,性能更加稳定.     

Clonal selection drives genetic divergence of metastatic medulloblastoma

Medulloblastoma, the most common malignant paediatric brain tumour, arises in the cerebellum and disseminates through the cerebrospinal fluid in the leptomeningeal space to coat the brain and spinal cord. Dissemination, a marker of poor prognosis, is found in up to 40% of children at diagnosis and in most children at the time of recurrence. Affected children therefore are treated with radiation to the entire developing brain and spinal cord, followed by high-dose chemotherapy, with the ensuing deleterious effects on the developing nervous system. The mechanisms of dissemination through the cerebrospinal fluid are poorly studied, and medulloblastoma metastases have been assumed to be biologically similar to the primary tumour. Here we show that in both mouse and human medulloblastoma, the metastases from an individual are extremely similar to each other but are divergent from the matched primary tumour. Clonal genetic events in the metastases can be demonstrated in a restricted subclone of the primary tumour, suggesting that only rare cells within the primary tumour have the ability to metastasize. Failure to account for the bicompartmental nature of metastatic medulloblastoma could be a major barrier to the development of effective targeted therapies.     

Clonal reproduction by males and females in the little fire ant

Sexual reproduction can lead to major conflicts between sexes and within genomes. Here we report an extreme case of such conflicts in the little fire ant Wasmannia auropunctata. We found that sterile workers are produced by normal sexual reproduction, whereas daughter queens are invariably clonally produced. Because males usually develop from unfertilized maternal eggs in ants and other haplodiploid species, they normally achieve direct fitness only through diploid female offspring. Hence, although the clonal production of queens increases the queen's relatedness to reproductive daughters, it potentially reduces male reproductive success to zero. In an apparent response to this conflict between sexes, genetic analyses reveal that males reproduce clonally, most likely by eliminating the maternal half of the genome in diploid eggs. As a result, all sons have nuclear genomes identical to those of their father. The obligate clonal production of males and queens from individuals of the same sex effectively results in a complete separation of the male and female gene pools. These findings show that the haplodiploid sex-determination system provides grounds for the evolution of extraordinary genetic systems and new types of sexual conflict.     

不同生境中慈竹克隆生长的密度调节

为了全面认识竹类植物克隆生长的密度调节机制，通过对两种生境的野外调查，本文在基株和分株两个层次上分析了慈竹克隆繁殖的数量和质量、竹笋高生长速度以及根茎长度等克隆生长特征与密度的关系．结果表明，慈竹的一些克隆生长特征(如：出笋数、死笋数、出笋速度、活笋基径和根茎长度)与分株密度呈不同程度的正相关，而竹笋高生长速度与分株密度无关．仅西山慈竹的出笋数和北湖公园的活笋数与基株密度呈显著的正相关．这些结果显示慈竹的克隆生长受分株密度和基株密度的共同调节，且以分株调节为主．不同生境中，慈竹克隆生长及其密度制约的规律存在差异．