Protein synthesis: its control in erythropoiesis

Erythropoiesis in the fetal mouse provides a model to study several important aspects of the regulation of cell differentiation and differentiated protein synthesis. Changes in the patterns of hemoglobins formed during fetal and postfetal development are shown to be associated with the substitution of the liver erythroid cell line. In the course of differentiation of yolk sac erythroid cells there are at least two classes of proteins distinguishable with respect to dependence on continued RNA formatoin. The bulk of nuclear proteins, "nondifferentiated" proteins, appear to be dependent on relatively short-lived messenger RNA while synthesis of differentiated proteins, the hemoglobins, proceeds on relatively stable molecules of messenger RNA. Hemoglobin formation occurs in those cells which are actively synthesizing DNA and dividing. On the average, two to three cell divisions may occur after the formation and stabilization of the messenger RNA for globin. Yolk sac erythropoiesis, at least from day 10 of gestation, is unresponsive to erythropoietin. By comparison, in fetal liver erythropoiesis, the hormone, erythropoietin, acts selectively on the most immature erythroid cell precursor to induce differentiation, cell replication, and hemoglobin formation. The erythropoietin responsive cell in the liver is apparently differentiated from the progenitor, pluripotential stem cell and committed to erythroblast formation and hemoglobin synthesis on exposure to the hormone. The initial effects of erythropoietin on macromolecular synthesis are to stimulate RNA synthesis, which temporally is followed by cell replication and the increase in hemoglobin formation. During liver erythropoiesis, there appears to be a transition from hemoglobin synthesis dependent on RNA formation to hemoglobin synthesis directed by relatively stable messenger RNA.     

Hemoglobin switching in sheep and goats: occurrence of hemoglobins A and C in the same red cell

Sheep and goats switch from the synthesis of hemoglobin A (alpha(2)beta(2)(A)) to hemoglobin C (alpha(2)beta(2)(C)) when made anemic. We have demonstrated the existence of the asymmetrical hybrid hemoglobin, alpha(2)beta(A)beta(C), in the circulating red cells of anemic sheep. These erythroid cells, therefore, synthesized both A and C hemoglobin simultaneously. Thus, the switch appears to be mediated by selective gene expression rather than by a clonal or cellular selective mechanism.     

军垦型美利奴羊的血清转铁蛋白分析

为了探索军型型,新疆型和澳大利亚型美利奴羊之间羊血清与主要生产性状之间的相关性,采用聚丙烯酰胺凝胶电泳法测定了３个品系的４７８只军垦型美利奴羊,１３２只新疆型美利奴羊和３９只澳大利亚美利奴羊的血清转铁蛋白。     

Replication of the B19 parvovirus in human bone marrow cell cultures

The B19 parvovirus is responsible for at least three human diseases. The virus was successfully propagated in suspension cultures of human erythroid bone marrow from patients with hemolytic anemias; release of newly synthesized virus into the supernatants of infected cultures was observed. This culture system allowed study at a molecular level of events associated with the B19 life cycle. The B19 parvovirus replicated through high molecular weight intermediate forms, linked through a terminal hairpin structure. B19 replication in vitro was highly dependent on the erythropoietic content of cultures and on addition of the hormone erythropoietin.     

Erythropoietin: hypothesis of action tested by analog computer

The action of erythropoietin on the pool of undifferentiated bone marrow cells has been examined with the aid of a model tested with an analog computer. The model is consistent with reported experimental results. The essential aspects of the action are (i) the effect is exerted during the S phase of the cell's cycle; (ii) " effective " erythropoietin is present in the cell only during G(1) and part of S; and, (iii) hormone molecules survive in the cell for only a limited time in effective form and require a certain time to assume this form.     

优质细毛羊的血清转铁蛋白分析

为了探索优质细毛羊型 ,新疆型和澳大利亚型美利奴羊之间羊血清Tf(转铁蛋白 )与主要生产性状之间的相关性 ,我们采用聚丙烯酰胺凝胶电泳法测定了 478只三个品系的军垦型美利奴羊 ,132只新疆型美利奴羊和 39只澳大利亚美利奴羊的血清转铁蛋白。结果表明 ,三个品系的优质细毛羊的优势基因都是Tfm ,Tfb优质细毛羊和新疆型美利奴羊之间 ,Tf基因均有显著的分布差异 ,显示优质细毛羊有其成为一个新的细毛羊品种的血清蛋白遗传学基础。优质细毛羊与新疆型美利奴羊以及澳大利亚美利奴羊Tf基因型分布频率不同 ,优势基因型分别为Tfmm(0 .42 1)、Tfbm(0 .2 88)、Tfcm(0 .2 82 )、优质细毛羊A ,B ,C三个品系的Tf基因型分布频率互有异 ,而同一品系内部公母羊之间的Tf基因型的分布则较相近 ,证明军垦型羊A ,B ,C三个品系的建立是有遗传学基础的。     

Hemoglobin Lepore trait: globin synthesis in bone marrow and peripheral blood

There was decreased synthesis of the beta-globin chain in the peripheral blood, and equal synthesis of alpha- and non-alpha-chains in the bone marrow of three patients with hemoglobin Lepore trait, similar to the findings in patients with heterozygous beta-thalassemia. There is a relative instability of the synthetic mechanism for normal beta-chain in these patients.     

Gene selection in hemoglobin and in antibody-synthesizing cells

Close linkage of mutually exclusive genes occurs in the non-alpha chain hemoglobin genes and in the immunoglobulin genes of man and other mammals. The expression of one gene in the cluster precludes the expression of any other linked gene. A simple, testable theory of gene selection called "looping-out excision"which was designed only to explain this mutual exclusivity in the hemoglobin system is described. The theory is closely concordant with a wide range of previously unexplained findings concerning hematopoiesis- including the developmental changes of hemoglobins, the increases in immature or fetal forms of hemoglobin that accompany anemia, and with the distribution of adult and fetal hemoglobins among erythrocytes during normal embryogenesis and in various pathological conditions. One corollary of this theory is that erythroid tissue in the normal adult bone marrow is constantly recapitulating the developmental stages of its embryogenesis. Another corollary is that the selection from among the linked globin genes occurs independently on the two chromosomes of the diploid organism. Both of these corollaries are supported by the available data. The same theory of gene selection is also remarkably consistent with known data for immunoglobulin synthesis; it could explain not only the mutually exclusive activation of linked variable genes but also the splicing which occurs between genetically linked variable and constant region genes for the immunoglobulin polypeptide chains. The agreement between these two different tissues is considered to be strong evidence that the proposed mechanism is correct at least in broad outline. Evidence from the genetics of maize and of drosophila also supports this theory of somatic tissue variegation. On the basis of these comparisons, I suggest that looping-out excision probably occurs also in other tissues and may be one means of gene selection and activation in differentiating cells.     

Corrections and clarifications

In the article "Molecular basis of mammalian sexual determination: Activation of Müllerian inhibiting substance gene expression by SRY" by C. M. Haqq et al. (2 Dec., p. 1494), parts B and C of figure 1 were inadvertently interchanged. In figure 3A, the third, fourth, and fifth lanes should have been labeled "A(7) --> T," "A(7) -->C," and "A(7) --> G," respectively. In figure 5, the factor labeled "SRIF's" should have been labeled "SRYIF's."     

Density gradient separation of marrow precursor cells restricted for antibody specificity

Potentially immunocompetent cells of (C57BL/6 x DBA/2) F(1) mouse bone marrow are committed to antigenic determinants of sheep or burro erythrocytes prior to interaction with thymus-derived cells and participation in immune responses to administered antigens. At this stage of differentiation marrow cells of this particular mouse strain are not yet restricted for the immunoglobulin M or immunoglobulin G antibody class. By equilibrium centrifugation in discontinuous gradients of bovine serum albumin, precursors of cells that produce antibody to sheep erythrocytes migrate to denser regions, whereas the precursors of immunocytes that produce antibody to burro erythrocytes remain in the lower density regions. cursors for all specificities.     

基于cytb基因探讨家绵羊和多角绵羊的系统发育

 【目的】研究中国家绵羊起源进化以及多角绵羊和普通家绵羊的亲缘关系。【方法】测定8个省区42个绵羊个体的细胞色素b基因全序列。【结果】本试验的绵羊个体可定义为40个单倍型,单倍型多样度为0.997±0.006,核苷酸多样度为0.793%。中国绵羊群体可分为4个支系(A、B、C 和D),其中支系D首次在中国绵羊群体中被检测到;支系B与支系C的差异最大,分化时间大约为595±150万年。多角绵羊与家绵羊聚在一起,而与野绵羊亲缘关系较远,分属于支系A、B和D。【结论】系统发育分析表明,中国绵羊有多个母系起源或经过多次驯化,未发现盘羊、东方盘羊和亚洲摩佛伦羊与绵羊母系祖先形成相关的分子证据。     

MTNR1A基因ExonⅡ T/C突变与绵羊季节性繁殖的关联性分析

【目的】分析MTNR1A基因ExonⅡ T/C突变与绵羊季节性繁殖性状的关联性,为深入研究MTNR1A基因在绵羊繁殖活动中的作用机制打下基础。【方法】以季节性繁殖的阿勒泰羊和中国美利奴羊(军垦型)及常年繁殖的湖羊和小尾寒羊为研究对象,采用PCR-SSCP及测序技术检测MTNR1A基因ExonⅡ T/C突变在4个绵羊品种群体中的分布情况,并分析其与绵羊季节性繁殖性状的关联性。【结果】MTNR1A基因ExonⅡ T/C突变致使MTNR1A蛋白的胞内无规卷曲结构域构象发生变化。在4个绵羊品种群体MTNR1A基因ExonⅡ处均可检测到T/C突变,其中阿勒泰羊和小尾寒羊中以TT基因型为主,T等位基因频率分别为C等位基因的3.4和11.2倍;在中国美利奴羊(军垦型)中则以TC基因型为主,TC基因型频率分别为TT和CC基因型的17.6和19.6倍;在湖羊中3种基因型的分布无明显差异。在阿勒泰羊群体中MTNR1A基因ExonⅡ T/C突变位点处于Hardy-Weinberg平衡状态(P>0.05),而在中国美利奴羊(军垦型)、湖羊和小尾寒羊群体中处于极度不平衡状态(P<0.01)。【结论】在季节性繁殖的阿勒泰羊和中国美利奴羊(军垦型)及常年繁殖的湖羊和小尾寒羊群体MTNR1A基因ExonⅡ处均可检测到T/C突变,但该突变与绵羊的季节性繁殖性状无关联。     

河西地区规模化羊场全舍饲条件下绵羊、山羊饲养繁育的研究

在规模化羊场舍饲条件下,对９个品系的绵羊、山羊的饲养繁育进行了初步的观察和研究,结果表明：全舍饲条件下饲养管理条件得到了很大的改善;夏洛来羊在所研究品种中初生重最大达（４５６±０３０）ｋｇ;３月龄体重达（２２３４±１２５）ｋｇ;从初生到３月龄的生长速度,无角陶赛特表现最快。研究组中山羊出生重最重的是安哥拉山羊,为（２３７±０２５）ｋｇ;对胸围、臀围等体尺进行的测量表明,其中夏洛来为最大,中卫山羊在山羊组中最大;血红蛋白的常规指标测定结果为,蒙古羊和中卫山羊基本表现正常,其他品种则表现较低,白细胞数量在所有品种中表现正常;采食行为中采食时间夏洛来、无角陶塞特、萨福克羊较其他品种短而反刍时间则较长;性成熟时间山羊晚于绵羊,舍饲绵羊、山羊在生产质量方面明显优于放牧羊。     

Transplantation of fetal hematopoietic stem cells in utero: the creation of hematopoietic chimeras

Transplantation of normal, immature, fetal hematopoietic cells into a preimmune fetal recipient with a congenital hemoglobinopathy may allow partial reconstitution of normal hemoglobin production without the complications associated with postnatal bone marrow transplantation (immunosuppression and the occurrence of graft versus host disease). In order to test this hypothesis the naturally occurring polymorphism at the beta-hemoglobin locus of the sheep was used as a marker for engraftment and hematopoietic chimerism. Intraperitoneal injection of allogeneic fetal stem cells into normal fetal lambs resulted in hematopoietic chimerism in three of four surviving recipients. This chimerism has been sustained for 6 months after birth and 9 months after engraftment, without evidence of graft versus host disease, and without the use of immunosuppressive therapy.     

贵德黑裘皮羊血液指标测定

[目的]为贵德黑裘皮羊的开发、利用及其疾病诊断和防治提供依据。[方法]采集青海省贵南县黑羊场15只成年健康贵德黑裘皮羊的血样,测定其红细胞、白细胞、血小板3分类18个血液指标。[结果]贵德黑裘皮羊的白细胞数为(7.52±2.72)×109个/L,红细胞数为(13.04±2.81)×1012个/L,血红蛋白含量为85.36±27.05g/L,红细胞平均容量为37.22±1.93fl,红细胞平均血红蛋白量13.19±0.96pg,血小板数为(370.67±139.60)×109个/L,淋巴细胞绝对值为(14.11±9.36)×109/L,中间细胞绝对值为(0.79±0.46)×109个/L,中性粒细胞绝对值(0.81±0.71)×109个/L。[结论]该研究为保护贵德黑裘皮羊以及发挥其优良生产性能奠定了基础。     

Adult hemoglobin synthesis by reticulocytes from the human fetus at midtrimester

The synthesis of adult-type hemoglobin was measured in small samples of peripheral blood cells from 9- to 18-week human fetuses. Hemoglobin indistinguishable from hemoglobin A was identified by ion-exchange chromatography, electrophoresis at pH 8.6, tryptic peptide analysis, and the insensitivity of its synthesis to the action of O-methylthreonine. Synthesis of hemoglobin A accounted for 8 to 14 percent of total hemoglobin synthesis and was demonstrated in as little as 10 microliters of fetal blood. These studies provide sensitive methods for the detection of beta chain types in hemoglobin synthesized by the human fetus at midtrimester. If methods to obtain small quantities of fetal blood at midtrimester become available, these techniques should be applicable to the antenatal detection of sickle cell anemia and related hemoglobinopathies.     

赖氨酸对绵羊GHR基因表达的影响

[目的]研究赖氨酸对绵羊生长的影响及其机理。[方法]选用1岁左右的绵羊15只,均分为A、B、C 3组,分别在基础日粮中添加0、4、10 g赖氨酸盐。饲喂28 d后,全部屠宰,取样。提取组织总RNA,反转录后扩增GHR和GAPDH基因,分析不同处理背最长肌中GHR mRNA的表达丰度。[结果]绵羊GHR基因在B组背最长肌组织中的表达量显著高于对照A组（P〈0.01）,极显著高于C组（P〈0.01）;C组与A组间差异不显著（P〉0.05）。[结论]在日粮中添加赖氨酸能够提高绵羊GHR基因在背最长肌中的表达量,但不存在剂量依赖性。     

Persisting circadian rhythm of cell division in a photosynthetic mutant of Euglena

A persisting, free-running, circadian rhythm of cell division in a heterotrophically grown mutant of Euglena gracilis var. bacillaris having impaired photosynthesis is obtained upon placing a culture that has been previously synchronized by a 10,14 light-dark cycle into continuous darkness at 19 degrees C (but not at 25 degrees C). A similar persisting rhythm is initiated in exponentially increasing cultures (growing in darkness at 19 degrees C) by a single "switch-up" in irradiance to continuous bright illumination. The results implicate an endogenous biological clock which "gates" the specific event of cell division in the cell developmental cycle.     

甘肃滩羊血红蛋白(Hb)及红细胞蛋白质(Ep)多态性的研究

运用聚丙烯酰胺凝胶电泳技术(PAGE)对甘肃滩羊产区皋兰、景泰及靖远3县285只滩羊的血红蛋白(Hb)基因座、红细胞蛋白质-1(Ep-1)和红细胞蛋白质-2(Ep-2)基因座多态性进行了检测,结果发现甘肃滩羊Hb基因座存在3种基因型HbAA、HbAB、HbBB,它们受HbA和HbB两个共显性等位基因控制,其中HbB和HbBB在3个群体中均占优势;本研究未在Ep-1和Ep-2基因座上检测到多态性,它们均呈现单态。     

乌珠穆沁羊遗传多样性与系统地位的研究

利用7个微卫星标记对乌珠穆沁羊、小尾寒羊、滩羊、湖羊、同羊、长江三角洲白山羊6个绵(山)羊群体进行了遗传多样性检测,结果显示:6个绵(山)羊群体共检测到224个等位基因,每个座位在每个群体都检测到7个以上等位基因;7个微卫星座位在6个群体中呈高度多态性,总群体杂合度为0.9499;6个群体PIC平均值在0.8452~0.9294之间。根据标准遗传距离和DA遗传距离用UPGMA方法分别对6个群体进行亲缘关系聚类,乌珠穆沁羊和小尾寒羊聚为一类,然后与滩羊聚为一类,湖羊和同羊较近聚为一类,五个绵羊品种最后与山羊相聚。研究结果提示:乌珠穆沁羊就血统而言归属与"蒙古羊"集团,这基本符合品种的育成过程,乌珠穆沁羊和小尾寒羊、滩羊、湖羊、同羊共同归属于"蒙古羊"集团。