Identification of a MHC class-II restricted epitope in carcinoembryonic antigen

Purpose The carcinoembryonic antigen (CEA) is extensively expressed on the vast majority of colorectal, gastric, and pancreatic carcinomas, and, therefore, is a good target for tumor immunotherapy. CD4+ T-helper (Th) cells play a critical role in initiation, regulation, and maintenance of immune responses. In this study, we sought to identify Th epitopes derived from CEA which can induce CEA-specific Th responses. The combined application with cytotoxic T lymphocyte (CTL) epitopes would be more potent than tumor vaccines that primarily activate CTL alone.Methods We utilized a combined approach of using a computer-based algorithm analysis TEPITOPE and in vitro biological analysis to identify Th epitopes in CEA.Results Initial screening of healthy donors showed that all five predicted peptides derived from CEA could induce peptide-specific T-cell proliferation in vitro. We characterized these CEA epitopes by establishing and analyzing peptide-specific T-cell clones. It was shown that CD4+ T-cells specific for the CEA₁₁₆ epitope can recognize and respond to naturally processed CEA protein and CEA₁₁₆ epitope can be promiscuously presented by commonly found major histocompatibility complex (MHC) alleles. Furthermore, it was demonstrated that immunization of human leukocyte antigen (HLA)-DR4 transgenic mice with CEA₁₁₆ peptide elicited antigen-specific Th responses which can recognize the antigenic peptides derived from CEA protein and CEA-positive tumors.Conclusion The MHC class II-restricted epitope CEA₁₁₆ could be used in the design of peptide-based tumor vaccine against several common cancers expressing CEA.     

寄生蜂对美洲斑潜蝇自然种群控制作用的评价

应用作用因子生命表方法以及在此基础上提出的排除作用控制指数法评价了寄生蜂对美洲班潜蝇自然种群的控制作用,结果表明,底比斯釉姬小蜂,丽潜蝇姬小蜂,冈崎釉姬小蜂,异角姬小蜂,黄潜蝇姬小蜂,甘蓝潜潜蝇茧蜂和离潜蝇的种群数量将比原各群增长1．23,2．73,5．98,5．92和5．71倍,在春季菜豆,豇豆,丝瓜和黄瓜上第2代美洲斑潜蝇中,若排除寄生蜂作用因子后,美洲斑潜蝇在上述4种蔬菜上的种群数量将分别多增长2．73,2．87,2．24和1．89倍,寄生蜂对美洲班潜蝇3龄幼虫的控制作用大于1龄,2龄幼虫和蛹的控制作用;春季美洲斑潜连续世代中,第1,2代寄生蜂的控制作用较第3,4,5代低,寄生蜂有菜豆和豇豆上的控制作用比在丝瓜和黄瓜上高。     

FKBP12 binding modulates ryanodine receptor channel gating

The ryanodine receptor (RyR1)/calcium release channel on the sarcoplasmic reticulum of skeletal muscle is comprised of four 565,000-dalton RyR1s, each of which binds one FK506 binding protein (FKBP12). RyR1 is required for excitation-contraction coupling in skeletal muscle. FKBP12, a cis-trans peptidyl-prolyl isomerase, is required for the normal gating of the RyR1 channel. In the absence of FKBP12, RyR1 channels exhibit increased gating frequency, suggesting that FKBP12 "stabilizes" the channel in the open and closed states. We now show that substitution of a Gly, Glu, or Ile for Val2461 in RyR1 prevents FKBP12 binding to RyR1, resulting in channels with increased gating frequency. In the case of the V2461I mutant RyR1, normal channel function can be restored by adding FKBP12.6, an isoform of FKBP12. These data identify Val2461 as a critical residue required for FKBP12 binding to RyR1 and demonstrate the functional role for FKBP12 in the RyR1 channel complex.     

Sirtuin1:抗炎治疗新靶点

Sirtuin 1(SIRT1)是组蛋白去乙酰化酶的代表性成员,除可调节代谢、衰老、凋亡外,SIRT1还可通过催化组蛋白及核因子κB(NF-κB)、激活蛋白1(AP-1)等的去乙酰化,从而改变染色质构象、降低转录因子活性、下调炎症基因转录。临床研究已揭示SIRT1在某些炎症性疾病中含量明显降低,而动物实验证实白藜芦醇、SRT1720等SIRT1激活剂可有效减轻炎症损伤。因而,SIRT1有望成为抗炎治疗的新靶点。     

冬眠周期长短不同的蒙古黄鼠（Citellus dauricus）...

Adult Mongolian ground squirrels (Citellus dauricus) were kept at 5 degrees C in winter and divided into four experimental groups according to the bout length. The first group was not hibernating until decapitation. The bout length of the second group was between 4-10 days, the third group 11-17 days and the fourth group longer than 20 days. All pineals were sampled at the end of January. Morphometric analytical procedures were used to study the ultrastructure of the distal part of the pineal gland. The statistical results demonstrated that 1) the euthermic animals have larger cross areas of pinealocyte, longer and narrower Golgi apparatus and more number of saccules of each Golgi apparatus (P less than 0.01). But they also have smaller volume density of vaculoes, less lipid droplets and associated vesicles around Golgi apparatus (P less than 0.01). 2) the hibernating animals with variety of bout length had no significant differences in the number of mitochondria, lipid droplets, lysosomes, the size of Golgi apparatus and the cross areas of nucleus and cytoplasm (P greater than 0.05). However, the number and the cross areas of vacuoles were significantly increased with the bout length (P less than 0.01). This might suggest that the bout length was not related to the metabolic activity of pinealocytes in Citellus dauricus and vacuoles might play some important roles in maintenance of individual bout of hibernation in this species.     

安徽山黧豆的核型

山黧豆属(又名香豌豆属)(Lathyrus Linn.)全世界共约140种,已做过染色体计数者72种。我国约16种,大部分产西南、西北和东北各省区。近年来皖南农学院朱玉简等同志在安徽宣城发现一新种,命名为安徽山黧豆(Lathyrus anhuiensis Y.J.Zhu et R.X.Meng)。鉴于该新种分布区非常局限,个体数也不多,为了及时掌握其细胞学情况,特通过该院叶如欣同志取得部分种子进行了染色体的计数和核型的描述。     

蜗牛酶对原生质体游离的影响

用10科11种双子叶植物的营养器官,在含1mg/L 2,4—D的MS固体培养基上诱导形成愈伤组织。取其生长旺盛的区域进行原生质体游离,并采用未经处理的相应植物的新鲜叶或茎作对照。研究结果表明,蜗牛酶对愈伤组织的原生质体游离具有明显的促进作用,而对照却无此效应。还研究了两种植物愈伤组织的继代天数和不同的酶组合对原生质体游离的影响。     

Red重组系统及在微生物基因敲除中的应用

在完成了对各种微生物基因组的测序以后,功能基因学的研究变得尤为重要。研究基因功能最直接的方法便是将待研究的基因失活。最初构建基因突变体是采用大肠杆菌的RecA系统,但是RecA重组系统操作复杂,重组效率低。最近建立了Red重组系统,该系统由3个蛋白组成：α蛋白(即λ核酸外切酶),β蛋白,Gam蛋白。应用Red系统进行基因敲除,可以直接利用线性打靶DNA,两侧同源臂长度在35~60 bp即可发生同源重组,且重组效率高。 Abstract:Since many DNA-sequencing projects of varied microorganisms have been completed,studies on their functional genomics become more important.Inactivation of an interesting gene is a direct method to characterize its function.Though the Esherichia coli RecA recombination system can be used to produce gene mutants,it needs a complex manipulation process.Furthermore,its efficiency is very low.Recently a Red recombination system was developed.This recombination system consists of three proteins:α protein（λ exonuclease）,β protein and Gam protein.In this system,the linear targeting DNA which contains a selectable marker flanked with a homologous region as short as only 35~60 bp can be directly targeted for gene knock-out with a higher efficiency.     

低压低氧延迟预适应小鼠海马差异表达蛋白的分离及鉴定研究

目的:探索低压低氧延迟预适应(HHDP)小鼠海马差异表达蛋白。方法:建立小鼠海马HHDP动物模型后,用含尿素的细胞裂解液提取海马总蛋白质。经等电聚焦、SDS-PAGE电泳、考马斯亮蓝R250染色,比较对照组及HHDP组双向电泳图谱上蛋白质点的差异。切取HHDP组表达增高的蛋白质点,经脱色、胰蛋白酶酶切、提取肽片段,进行MALDI-TOF-MS检测。结果:在正常对照组和HHDP组海马总蛋白双向电泳图谱上,分别检测到481±38和477±21个点,匹配点为169±6个。其中HHDP组比对照组增高大于2倍的有33±10个点,降低大于2倍的有21±12个点。电泳图谱平均相关系数为0.7748±0.0267。有12个点在HHDP组显著增高(P<0.05,n=4),对其进行了肽质量指纹图谱分析,其中8个蛋白点得到相应的肽质量指纹图谱。数据库检索显示其中一个为果糖二磷酸醛缩酶A。3个在蛋白质数据库中没有检索到与之相匹配的任何蛋白,可能为新蛋白。另外4个可找到与其有部分匹配的氨基酸序列,但分子量和等电点与对应蛋白相差悬殊,它们可能具有同源性。结论:小鼠海马HHDP时,果糖二磷酸醛缩酶A等多种蛋白表达发生改变,可能是产生HHDP的重要机制之一。