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The 20S catalytic core of the 26S proteasome has the shape of a barrel made of four rings which are composed of seven differentαsubunitsα_1-α_7 at two outer rings and seven differentβsubunitsβ_1-β_7 at two inner rings at which the catalytic sites locate. Three of theβsubunits contain proteolyses sites, which are sequestered in the hollow interior of the 20S particle. Substrates enter the 20S through a narrow channel formed by theβsubunits, whose N-termini, depending on their conformation, can either obstruct or allow substrate entry and thus function as a gate. This entry channel is narrow and only permits passage of unfolded, linearized polypeptides.

哺乳动物26S蛋白酶体是由一个20S催化颗粒(catalytic particle,CP)和两个19S调节颗粒(regulatory particle,RP)组成的ATP(adenosine-triphosphate,ATP)依赖性蛋白水解酶复合体。20S CP是26S蛋白酶体的催化核心,它是由4个圆环堆叠形成的桶状复合物,其中两侧外环每个环是由α_1-α_7亚基组成,两个内环每个环是由β_1-β_7亚基组成,4个环的中央形成一个狭窄的内腔。2个β内环形成了20S CP的催化中心空腔,其内壁为催化活性位点所在地;外侧α环中心的孔道是底物到达催化中心空腔的通道,一般被α亚基上的N末端所封闭,阻止胞内非目的靶蛋白进入20S CP内被降解破坏。

Majority of acute leukemias in infant, either acute lymphoblastic leukemia or acute myeloblastic leukemia, posses a chromosomal translocation affecting the 11q23 chromosome region which specifically inoles the mixed-lineage leukemia gene.1-3 Most pediatric leukemias with MLL rearrangement clearly hae a remarkably short latency.1,4 MLL gene rearrangement is also associated with secondary leukemias of patients preiously treated with the topoisomerase II inhibitors.4 The latency of these secondary leukemias is similarly ery short.4 Of note, the concordance rate of leukemia with MLL rearrangement in infant monozygotic twins approximates to 100%,1,4 and identical breakpoint in the MLL gene was shared in these pairs of identical twin infants with concordant ALL.1,4 Moreoer, the unique and clonotypic MLL fusion gene was detectable in neonatal blood spots for Guthrie cards from non-twined indiiduals who subsequently deeloped ALL.1,4 These obserations indicate not only that MLL fusion is generated in utero but also that MLL fusion proteins could be capable of inducing leukemic transformation with few, if any, secondary mutations.2,3,4 Greaes et al speculate that an MLL fusion protein somehow promotes rapid transition to full-blown disease in patients ia ery rapid clonal expansion, genetic instability, or inhibition of DNA damage repair.4 In general, for clonal expansion of malignancies, tumor cells often hae acquired strategies that escape immune sureillance of the hosts.5,6 Immune escape mechanisms also contribute to the failure of graft-ersus-leukemia effect after allogeneic hematopoietic stem cell transplantation.7 Therefore, leukemia cells could acquire some immune escape mechanisms during leukemogenesis.

绪论 绝大多数的婴儿白血病,不管是急性淋巴性白血病或是急性骨髓性白血病,在染色体11q23部位有染色体易位的情况;这个部位的染色体易位牵连了混合谱系白血病基因。大多数具有MLL基因重排的儿童白血病潜伏期明显短很多。MLL基因重排也和经拓扑异构酶II抑制剂治疗后的继发性白血病有关。这些继发性白血病的潜伏期类似地都非常的短。很重要的是,单卵双胞胎婴儿同时患有或同时免于MLL基因重排阳性的白血病的一致性接近100%;并且同样患有ALL的同卵双胞胎的MLL基因的断裂点是一致的。而且,这种独特的克隆特异性的MLL融合基因能够从那些得ALL的非双生个体出生时的血斑标本中检测到。这些发现表明MLL融合基因产生在胎儿还在子宫的是后,而且MLL融合蛋白能过和其他的基因突变一起诱导白血病的产生。Greaes 等推测MLL融合蛋白在某种情况下同过快速克隆增殖,遗传的不稳定性或是DNA损伤修复的抑制促使疾病迅速地全面爆发。恶性肿瘤细胞的克隆增殖通常已经获得了逃避机体免疫监视的能力。免疫逃避机制也归因于异体外周血干细胞移植后移植物抗白血病作用的失效。所以,白血病细胞在白血病的产生过程中可能获得了某些免疫逃脱机制。

Recently, it is found that the neuron apoptosis caused by brain ischemia is associated with signal pathway of endoplasmic reticulum stress, which is different from the traditional apoptotic pathway. Caspase-12 has been identified as a molecule which initiates apoptosis selectively in response to ER stress and is not activated by other pathways. Caspase-12 is localized on the ER membrane, but once specifically activated by ER stress, it translocates to the cytoplasm.

最近的研究发现,这种细胞凋亡与内质网应激(endoplasmic reticulum stress ER stress)有关,其是一种不同于经典的凋亡途径的新途径,分子伴侣葡萄糖调节蛋白78(glucose regulated protein, GRP78/Bip)表达增高是反应ER stress的最敏感的指标,胱冬酶-12(caspase-12)为鼠源性的内质网膜上的蛋白,它的特点是只被内质网诱导的凋亡所激活而不被其它非内质网因素所激活。

These results suggested that the function of each function domain in HIV 1 LTR exhibited distinct characteristics on gag gene expression in vaccinia virus:(1) The function of intact LTR on gag gene expression varied with the upstream poxvirus promoter;(2) NR sequence neither decreased nor increased the Gag protein exprssion level;(3) Enhancer sequence might not be recognized by recombinant vaccinia virus expression system;(4) TAR sequence enhanced Gag protein expression effectively;(5) U5 region and its downstream non translated sequence had little effect on

免疫印迹和免疫酶试验检测均表明,6株重组病毒的Gag蛋白表达量因LTR不同而有明显差异,表明HIV1的LTR及其下游基因置于痘病毒启动子控制下,在痘苗病毒中表达时有下述特点:(1)不同的痘苗病毒启动子与全长LTR相互作用,对gag基因表达有显著不同的调控效果;(2)NR序列对Gag蛋白表达没有明显影响;(3)EN序列不能被重组痘苗病毒表达系统识别;(4)TAR序列可提高Gag蛋白的表达量;(5)U5区及下游非翻译序列不影响Gag蛋白的表达。

The results indicated that the accumulation of Mn in the cell wall (accumulation rate as high as 36.34%) and the vacuole of the leaves (accumulation rate as high as 65.64%) might be one of the mechanisms of tolerance and hyperaccumulation of Polygonum hydropiper to Mn. Most Mn in leaves were the speciation of H2O-solubility organic salts or manganese oxalates. The content of chlorophyll a did not change under different Mn concentration treatments except that its content decreased remarkably when Mn concentration was 8000μmol/L in solutions. The membranes were not banned by Mn when its concentration was less than 5000μmol/L in solutions; Under different Mn concentrations of Mn, the content of their soluble proteins of leaves had changed at some stage. The activity of SOD and POD were gradually improved with the increasing of Mn concentration, which could eliminate activated oxygen free radical, This might be the other physiological mechanism of tolerance and hyperaccumulation of Polygonum hydropiper responding to Mn.

结果表明:锰在水蓼叶片非活性代谢部分的积累是其解毒耐锰的主要机制之一;水蓼叶片中的锰大部分以水溶性有机盐或草酸锰的形态存在;在锰浓度处理为8000μmol/L时,叶绿素a含量显著降低,而在其它处理条件下,叶绿素a无明显变化;在锰处理≤5000μmol/L时水蓼叶片的细胞膜还没有受到明显伤害;水蓼叶片的可溶性蛋白含量随锰处理浓度不同而变化,说明植物在代谢和结构上发生了调整;随锰处理浓度的增加,水蓼叶片SOD和POD活性提高,保护酶活性的提高又可清除活性氧自由基,这是水蓼耐高锰和累积锰的一种生理响应机制。

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According to the clear water experiment, aeration performance of the new equipment is good with high total oxygen transfer coefficient and oxygen utilization ratio.

曝气设备的动力效率在叶轮转速为120rpm~150rpm时取得最大值,此时氧利用率和充氧能力也具有较高值。

The environmental stability of that world - including its crushing pressures and icy darkness - means that some of its most famous inhabitants have survived for eons as evolutionary throwbacks, their bodies undergoing little change.

稳定的海底环境─包括能把人压扁的压力和冰冷的黑暗─意谓海底某些最知名的栖居生物已以演化返祖的样态活了万世,形体几无变化。

When I was in school, the rabbi explained everythingin the Bible two different ways.

当我上学的时候,老师解释《圣经》用两种不同的方法。