Stereoselective synthesis of radiolabelled avermectins

The natural products avemectin B _1a 1a and B _1b 1b were each site‐specifically ¹⁴C labelled at carbon 23 in a convergent synthesis for metabolism, residue, and environmental studies. The 12‐step radiosynthesis involved a stereoselective aldol condensation and later a coupling to a protected avermectin degradate 2 in a one‐pot Wittig condensation/spiroketalization to reconstitute the dioxaspirane configuration found in the natural products. Copyright © 2004 John Wiley & Sons, Ltd.     

Investigation of epididymal sperm maturation in the golden hamster

During passage of hamster spermatozoa through the epididymis their maturation is shown to involve changes in the sperm head, midpiece (mitochondria) and tail. The sum of these changes results in a dramatic increase in the fertilizing potential of the spermatozoa. When comparable numbers of spermatozoa from the caput or corpus epididymis were injected into one uterine horn of mature females, following ovulation induction, and spermatozoa from the cauda epididymis were injected into the contralateral horn, no fertilization was observed with caput epididymal spermatozoa, 1.7% of oocytes were fertilized by corpus epiddymal spermatozoa, whereas 79.5% fertilization was obtained with cauda epididymal spermatozoa. Total sperm numbers increased from caput to corpus to cauda [28.3 ± 12.2, 40.6 ±20.8, 1434 ±62 mihon, respectively]. The percentage of progressively motile spermatozoa increased from 27.9 ±6.4 to 33.8 ± 4.8 to 70 ± 10.7 during this passage. Viability, measured by exclusion of the dye, propidium iodide, was significantly less in spermatozoa from the cauda than from the proximal or mid-caput epididymis. The percentage of the live cells that were stained intensely by rhodamine-123 (a measure of mitochondrial membrane potential) increased during epididymal passage from 22.8 ±7.8% in the proximal caput epididymis to 57.2 ± 16.5% in the cauda epididymis. Staining with acridine orange (a measure of DNA packaging in the sperm head) indicated an increase in chromatin condensation in cauda epididymal spermatozoa, when compared to those obtained from the caput or corpus.     

Formation of Regular Hole Pattern in Polymer Films

Ordered macroporous materials recently have attracted much attention. A method that utilizes the condensation of monodisperse water droplets on a polymer solution is proposed for the preparation of honeycomb microporous films. Our results show that it is a general method that can be used for patterning a wide range of polymers. The presence of water vapor and polymer is necessary for the formation of regular holes in films. The formation of hexagonal packing instead of other kinds of packing takes place because the hexagonal packing has the lowest free energy. The formation mechanisms of regular hole pattern and imperfections in the hexagonal packing are proposed.

Hexagonal hole structures in a PMMA film.     

5-Azacytidine produces differential undercondensation of alpha,beta and classical human satellite DNAs

Fluorescencein situ hybridization employing human alphoid, beta and classical satellite DNA probes was performed on 5-azacytidine treated and untreated chromosomes obtained from human lymphocytes. The individual used in this study presented a polymorphism of constitutive heterochromatin of chromosomes 1 and 9 as revealed byin situ digestion with the restriction endonucleaseAlul. Neither the alphoid nor the beta satellite DNA domains were susceptible to condensation-inhibition by 5-azacytidine. Only the classical satellite localized on chromosome 9 was affected. The constitutive heterochromatin size polymorphism was shown to depend mainly on variations of the classical satellite DNA domain. Therefore, condensation-inhibition, as a phenomenon which may modify the natural folding of the chromatin fibre, regionally affects human constitutive heterochromatin and seems to be dependent on the heterochromatic family.     

Induction of chromosome aberrations and mitotic arrest by cytomegalovirus in human cells

Human cytomegalovirus (CMV) is potentially an effective but often overlooked genotoxic agent in humans. We report here evidence that indicates that infection by CMV can induce chromosome alterations and mitotic inhibition. The frequency of chromosome aberrations induced was dependent on the input multiplicity of infection (m.o.i.) for human lung fibroblasts (LU), but not for human peripheral blood lymphocytes (PBLs) when both cell types were infected at the GO phase of the cell cycle. The aberrations induced by CMV were mostly chromatid breaks and chromosome pulverizations that resembled prematurely condensed S-phase chromatin. Pulverized chromosomes were not observed in LU cells infected with virus stocks that had been rendered nonlytic by UV-irradiation at 24,000 ergs/mm2 or from infection of human lymphocytes. In LU cells infected with UV-irradiated CMV, the frequency of aberrations induced was inversely dependent on the extent of the exposure of the CMV stock to the UV-light. In permissive CMV infection of proliferating LU cells at 24 hr after subculture, a high percentage (greater than 40%) of the metaphase cells were arrested at their first metaphase and displayed severely condensed chromosomes when harvested 48 hr later. A significant increase (p less than 0.05) in the chromosome aberration frequency was also observed. Our study shows that CMV infection is genotoxic to host cells. The types and extent of damage are dependent on the viral genome expression and on the cell cycle stage of the cells at the time of infection. The possible mechanisms for induction of chromosome damage by CMV are discussed.     

Blood serum as a factor in chromatin condensation in trisomy-21 (Down's syndrome)

The effect on the blood serum of patients with Down's syndrome and of healthy persons and also separate fractions of sera on structural parameters of model nucleohistone systems (DNP-systems) was studied. Unfractionated patients' sera were found to have a condensing effect on DNP-systems, unlike healthy human sera. Analysis of the action of the individual serum fractions showed that different degrees of condensation can be attributed to the influence of high-molecular weight, undialyzable, thermolabile components, the action of which disappears after gel-filtration of the serum proteins. The problem of possible humoral control over the structural organization of chromatin in vivo is discussed in the light of data showing similarity between blood serum proteins and certain nonhistone proteins of chromatin.Laboratory of Molecular Biology, Institute of Medical Genetics, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. P. Bochkov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 10, pp. 460–463, October, 1979.     

Histone deacetylase activity is necessary for chromosome condensation during meiotic maturation in Xenopus laevis

Chromosome condensation is thought to be an essential step for the faithful transmission of genetic information during cellular division or gamete formation. The folding of DNA into metaphase chromosomes and its partition during the cell cycle remains a fundamental cellular process that, at the molecular level, is poorly understood. Particularly, the role of histone deacetylase (HDAC) activities in establishing and maintaining meiotic metaphase chromosome condensation has been little documented. In order to better understand how metaphase chromosome condensation is achieved during meiosis, we explored, in vivo, the consequences of HDAC activities inhibition in a Xenopus oocyte model. Our results show that deacetylase activity plays a crucial role in chromosome condensation. This activity is necessary for correct chromosome condensation since the earlier stages of meiosis, but dispensable for meiosis progression, meiosis exit and mitosis entry. We show that HDAC activity correlates with chromosome condensation, being higher when chromosomes are fully condensed and lower during interphase, when chromosomes are decondensed. In addition, we show that, unlike histone H4, Xenopus maternal histone H3 is stored in the oocyte as a hypoacetylated form and is rapidly acetylated when the oocyte exits meiosis.     

体内外自由基形成的研究及意义

目的研究体内外自由基的形成及意义。方法用TBA-醋酸法检测正常人血清,血浆,胸腹腔渗、漏出液,各细胞提取物及服用西洋参前后的血浆和经过氧化处理后的正常人、糖尿病、高血压、冠心病患者的血清及食用油脂、相应烟雾冷凝油的过氧化脂质(LPO)含量。结果各细胞均有自由基反应,以血小板为最高。血清LPO明显高于血浆(P<0.001),胸腹腔渗出液LPO明显高于漏出液(P<0.001),过氧化处理后的糖尿病、高血压、冠心病患者血清的LPO明显高于过氧化处理后的正常人血清LPO(P<0.001);油脂质量越高,LPO含量越低,相应的烟雾冷凝油的LPO是食用油脂的14.3～35.6倍。结论生物、化学和物理因素均可引起脂质过氧化,不管何种因素所致的脂质过氧化,其反应过程及其产物LPO对生物体都有严重的损害作用。     

酮基布洛芬的合成方法改进

目的 合成酮基布洛芬，提高产品纯度。方法 以3—苄基苯乙酮为原料，通过Darzens缩合，氧化合成目标物。结果与结论 以3—苄基苯乙酮计算，总收率约64％，产品纯度为99．8％。并通过红外吸收光谱(IR)、质谱(Ms)确证了目标物的结构。该合成工艺简单，产品质量好。