赤霉素A4,A7的研究进展

赤霉素Ａ＿４、Ａ＿７的研究进展颜方贵,秦杰,何增国,李季伦（北京农业大学生物学院,北京１０００９４）赤霉素Ａ＿３（ＧＡ＿３）是目前应用最广的植物生长激素之一。随着研究的深入,对该族的其它同系物,特别是ＧＡ＿４、ＧＡ＿７越来越受到重视,这是由于ＧＡ＿４...     

Synthesis of 27-Oxo, 27-Hydroxymilbemycins A3 and A4 and Novel 27-Alkoxymilbemycins A3 and A4 from Milbemycins A3 and A4 and…

27-Oxomilbemycins A₃ and A₄ and 27-hydroxymilbemycins A₃ and A₄ were identified as metabolites in soil metabolism studies of milbemycins A₃ and A₄. Chemical derivation methods were developed to synthesize 27-oxomilbemycins A₃ and A₄ and 27-hydroxymilbemycins A₃ and A₄ from milbemycins A₃ and A₄. In addition, 27-alkoxymilbemycin derivatives were also synthesized from the same precursors. Some of the synthesized compounds displayed satisfactory acaricidal activity against the organophosphorus-sensitive two-spotted spider mite (Tetranychus urticae), but did not have superior activity to corresponding milbemycins A₃ and A₄.     

赤霉素A4、A7的发酵研究

初选藤仓赤霉菌(Gibberella fujikuroi)农大17菌株为赤霉素A_4、A_7(GA_4、GA_7)的生产菌,该菌株GA_(4+7)的积累量,除与营养条件有关外,温度和pH是极为重要的因子,随着发酵温度从28℃上升至32℃,GA_(4+7)的产量由21μg/ml增至81μg/ml,GA_3由702μg/ml降至328μg/ml。pH回调至中性,GA_(4+7)的产量由75μg/ml增至180μg/ml,GA_3由322μg/ml降至211μg/ml。此外,设法延长发酵周期也是增加GA_(4+7)的一个因素。综合上述条件,即发酵过程中,发酵液的pH由48h前的4回调并维持在6.7左右,温度由28℃上调并控制在32℃,摇瓶培养12天,GA_(4+7)的产量达890μg/ml,20—600L发酵罐发酵240h,GA_(4+7)产量达680μg/ml左右。GA_(4+7)浓度的测定亦作了简化处理,发酵液不经提取,可直接用硅胶板G薄层层析(TLC)后进行荧光比色,产品测定宜采用高效液相色谱法(HPLC)。按照上述条件培养的农大17菌株,产生GA_3、GA_7和GA_4的比例为23.131:16.105:31.258,GA_4高于有关报道。     

Targeting lysine specific demethylase 4A (KDM4A) tandem TUDOR domain – A fragment based approach

The tandem TUDOR domains present in the non-catalytic C-terminal half of the KDM4A, 4B and 4C enzymes play important roles in regulating their chromatin localizations and substrate specificities. They achieve this regulatory role by binding to different tri-methylated lysine residues on histone H3 (H3-K4me3, H3-K23me3) and histone H4 (H4-K20me3) depending upon the specific chromatin environment. In this work, we have used a 2D-NMR based fragment screening approach to identify a novel fragment (1a), which binds to the KDM4A-TUDOR domain and shows modest competition with H3-K4me3 binding in biochemical as well as in vitro cell based assays. A co-crystal structure of KDM4A TUDOR domain in complex with 1a shows that the fragment binds stereo-specifically to the methyl lysine binding pocket forming a network of strong hydrogen bonds and hydrophobic interactions. We anticipate that the fragment 1a can be further developed into a novel allosteric inhibitor of the KDM4 family of enzymes through targeting their C-terminal tandem TUDOR domain.     

4.—A FIELD-NATURALISTS PEREGRINATIONS

Geldenhuys, J. N. 1983. Morphological variation in wing-moulting South African Shelducks. Ostrich 54:19-25. Male and female South African Shelducks Tadorna cana lose 25,6 and 28,2% of their pre-moult weight during the flightless period. Juveniles (3–5 months old) do not take part in the wing-moult aggregation. Subadults (15–17 months old) cannot be distinguished from older birds in wing-moulting populations on the basis of the bursa of Fabricius, penis structure, colour of the wing feathers, foot colour and the size of the culmen and tarsus. It is suggested that the catabolism of body tissue during wing-moult has little effect on the survival of the species.     

Charon 4A噬菌体DNA的制备

由David改造的Charon 4A噬菌体,目前已普遍作为无性繁殖各种DNA的良好载体。它具有极好的安全性。Charon 3A、4A和16A噬菌体已被确定为EK_2级的载体——宿主系统。 Charon 4A噬菌体DNA为46kb碱基对长。经EcoRI酶消化成4个片段,其中19和12kb片段可作为制备真核基因文库的载体,可     

CUL4A作用机制研究进展

Cullin4A (CUL4A)是泛素-蛋白酶体系统(ubiquitin-proteasome system,UPS)中泛素E3连接酶家族的重要成员之一.UPS是细胞内蛋白降解的重要途径,越来越多的证据表明CUL4A可以通过CUL4A-DDB1-E3途径调节细胞中的一些功能蛋白质,产生相应的作用.本文就CUL4A在基因组的稳定、细胞周期的调控、恶性肿瘤的发生发展、胚胎发育、造血干细胞及脑缺血性损伤等方面的作用进行综述.     

Charon 4A噬菌体DNA的制备

由David改造的Charon 4A噬菌体，目前 已普遍作为无性繁殖各种DNA的良好载体。 它具有极好的安全性。Charon 3A, 4A和16A 噬菌体已被确定为EK,级的载体— 宿主系 统^[1,2,4,5]     

A short synthesis of 4-deoxy-4-fluoroglucosaminides: Methylumbelliferyl N-acetyl-4-deoxy-4-fluoro-β-D-glucosaminide

A convenient method of synthesis of 1,6-anhydro-4-deoxy-2-O-tosyl-4-fluoro-β-D-glucopyranose by fusion of 1,6;3,4-dianhydro-2-O-tosyl-β-D-galactopyranose with 2,4,6-trimethylpyridinium fluoride was found. By a successive action of ammonia, methyl trifluoroacetate, and acetic anhydride, the resulting compound was transformed into 1,6-anhydro-3-O-acetyl-2,4-dideoxy-2-trifluoroacetamido-4-fluoro-β-D-glucopyranose, which was converted into 3,6-di-O-acetyl-2,4-dideoxy-2-trifluoroacetamido-4-fluoro-αD-glucopyranosyl fluoride by the reaction with HF/Py. The resulting fluoride was further used as a glycosyl donor in the synthesis of methylumbelliferyl N-acetyl-4-deoxy-4-fluoro-β-D-glucosaminide.     

噬菌体Charon4A增殖条件的研究

噬菌体Chmon 4A是噬菌体λ经过改建而成的,可用作基因工程的载体。由于这种噬菌体载体与相应的宿主菌Escherichia coil DP50supF一起成为EK_2级安全宿主载体系统,同时     

Synaptotagmin 4: A New Antiobesity Target?

In this issue of Neuron, Zhang et?al. show that Synaptotagmin 4 (Syt4) is specifically induced in adult hypothalamic oxytocin neurons by high-fat diet. Evidence is provided to support a critical role for Syt4 in negative regulation of oxytocin release, which in turn is responsible for diet-induced obesity, raising the possibility of using Syt4 as a new antiobesity target.     

A new synthesis of 4-O-α-d-galactopyranosyl-d-galactopyranose

The bromide-catalyzed condensation of 2,3,4,6-tetra-O-benzyl-d-galactopyranosyl bromide (11) with methyl 2,3,6-tri-O-benzoyl-α-d-galactopyranoside (3) gave methyl 2,3,6-tri-O-benzoyl-4-O-(2,3,4,6-tetra-O-benzyl-α-d-galactopyranosyl)-α-d-galactopyranoside (12) in 83% yield. The yield of this glycosidation reaction was high, despite the axial orientation of the 4-hydroxyl group of 3. Stepwise deprotection of 12 afforded methyl 4-O-α-d-galactopyranosyl-α-d-galactopyranoside (15). Acetylation of 15, followed by acetolysis, gave the known α-octaacetate 17. This scheme constituted a total synthesis of 4-O-α-d-galactopyranosyl-d-galactopyranose (2) in 25% yield from 3. The disaccharide 2 is the terminal disaccharide of the ceramide trisaccharide related to Fabry's disease.     

A fascinating island: 2n = 4

Abstract

Among Angiosperms, only six species are known to possess the lowest identified chromosome number, i.e. 2n = 4. These plants are the monocotyledons Zingeria biebersteiniana, Colpodium versicolor, Ornithogalum tenuifolium and Rhynchospora tenuis, and the dicotyledons Haplopappus gracilis and Brachyscome dichromosomatica. The low chromosome number may be cytogenetically derived from a different ancestral basic number, characteristic of each genus, by different processes, including tandem fusion or unequal reciprocal translocations with loss of centric fragments. All these plants possess low nuclear 4C DNA contents, ranging from 1.56 pg (R. tenuis) to 8.20 pg (H. gracilis), and they generally display a similar chromosome size and a similar position of the nucleolus organising region (NOR), that is often located in the terminal or subterminal region of the small chromosome pair. All these characteristics could be a consequence of common adaptative mechanisms. Peculiar characteristics within these karyotypes are the holocentric chromosomes of R. tenuis and the presence of B chromosomes in B. dichromosomatica. Plants with a very low chromosome number may be considered to constitute a fascinating “island of interest”; moreover, they represent simple systems helpful for the examination of the structural organisation and evolution of Angiosperm chromosomes.     

S100A4 在胰腺癌中的研究进展

胰腺癌最重要的生物学特性是容易发生转移和侵袭,致使很多患者无法得到根治性治疗。外科手术是胰腺癌惟一可能治愈的手段,但仅有10-20%的患者有机会手术治疗。错过早期诊断、常规疗法普遍不明显及快速肿瘤扩散共同导致患者的预后不良。胰腺癌的发生、发展受多基因调控。S100A4基因是近几年发现的一种具有促肿瘤作用的基因,目前研究认为该蛋白在胰腺癌的侵袭和转移中起重要作用.本文主要就S100A4与胰腺癌的有关研究进展加以综述。     

CYP3A4基础与临床研究进展

细胞色素P4503A4(CYP3A4)是存在人类肝脏及肠道中的一种主要的细胞色素CYP450酶,约占成人肝脏CYP450酶总量的25%左右。临床中约有50%的药物是通过其代谢,并且其基因位点突变也与其多种疾病相关,知晓CYP3A4的表达水平和不同功能的遗传学基础,无论是对疾病的发病基础、临床药物的应用,会带来前所未有的启发,在药物应用过程中,通过对基因组学的认识,从而可以在基因层面了解个体代谢差异产生的原因,调整药物用量,提高疗效,最终使药物副作用降到最低限。目前对CYP3A4的研究渐趋于成熟,已逐渐阐明了其药物间相互作用的机制,它能够被多种药物竞争性抑制或者诱导,并受到某些蛋白受体的调控影响,可改变药物的药代动力学,增强或降低药效,造成个体用药差异,这也是造成药物间相互作用的重要原因。然而CYP3A4基因多态性与基因导向治疗关系,还有待进一步深入研究。该文对CYP3A4基因多态性、分布以及与临床疾病及用药的研究现状作一综述。     

S100A4在胰腺癌中的研究进展

胰腺癌最重要的生物学特性是容易发生转移和侵袭,致使很多患者无法得到根治性治疗。外科手术是胰腺癌惟一可能治愈的手段,但仅有10-20%的患者有机会手术治疗。错过早期诊断、常规疗法普遍不明显及快速肿瘤扩散共同导致患者的预后不良。胰腺癌的发生、发展受多基因调控。S100A4基因是近几年发现的一种具有促肿瘤作用的基因,目前研究认为该蛋白在胰腺癌的侵袭和转移中起重要作用.本文主要就S100A4与胰腺癌的有关研究进展加以综述。     

Effect of vitamin A deficiency on thymosin-β4 and CD4 concentrations

Vitamins are evaluated for their role in immunity. Recently, vitamin A received a particular attention as a critical micronutrient for regulating immune system. Therefore, the present study aimed to search for new about vitamin A. Forty-eight Egyptian adults aged from 18 to 42?years old from both sexes were subjected to clinical examination and nutrition questionnaire and were screened for vitamin A by using ELISA method. Forty subjects were selected and subdivided into two groups. Group 1 with vitamin A at level >200?µg/dl consists of 10 healthy subjects. Group 2 with vitamin A deficiency at level <50?µg/dl consists of 30 subjects. Tβ4 and CD4 levels were also determined by a commercial ELISA kit. Results showed a significant decrease in serum levels of Tβ4 and CD4 in group 2 than group 1 at P < .003 and P < .019 respectively. Both of Tβ4 and CD4 had positive correlation with vitamin A level at P < .000 and P < .003 respectively as well as with each other at p < .000. We concluded that vitamin A deficiency may be influence the levels of Tβ4 and CD4.