Altered replication in human cells promotes DMPK (CTG)(n) · (CAG)(n) repeat instability

Myotonic dystrophy type 1 (DM1) is associated with expansion of (CTG)(n) · (CAG)(n) trinucleotide repeats (TNRs) in the 3' untranslated region (UTR) of the DMPK gene. Replication origins are cis-acting elements that potentiate TNR instability; therefore, we mapped replication initiation sites and prereplication complex protein binding within the ~10-kb DMPK/SIX5 locus in non-DM1 and DM1 cells. Two origins, IS(DMPK) and IS(SIX5), flanked the (CTG)(n) · (CAG)(n) TNRs in control cells and in DM1 cells. Orc2 and Mcm4 bound near each of the replication initiation sites, but a dramatic change in (CTG)(n) · (CAG)(n) replication polarity was not correlated with TNR expansion. To test whether (CTG)(n) · (CAG)(n) TNRs are cis-acting elements of instability in human cells, model cell lines were created by integration of cassettes containing the c-myc replication origin and (CTG)(n) · (CAG)(n) TNRs in HeLa cells. Replication forks were slowed by (CTG)(n) · (CAG)(n) TNRs in a length-dependent manner independent of replication polarity, implying that expanded (CTG)(n) · (CAG)(n) TNRs lead to replication stress. Consistent with this prediction, TNR instability increased in the HeLa model cells and DM1 cells upon small interfering RNA (siRNA) knockdown of the fork stabilization protein Claspin, Timeless, or Tipin. These results suggest that aberrant DNA replication and TNR instability are linked in DM1 cells.     

A boy with 47,X,del(X)(p11→q13::q21→q24),del(Y)(q11)

Summary A patient is described carrying a duplication 4p12pter due to a paternal translocation: 46,XY,t(4;16) (p12;p13). Involvement of chromosome No. 16 and the heterogeneity of the clinical picture in cases with dup (4p) are discussed.Postdoctoral fellow of the Deutsche Forschungsgemeinschaft.     

Microsolvation and hydration enthalpies of CaC2O4(H2O) n (n = 0-16) and C2O4 2-(H2O) n (n = 0-14): an ab initio study

We studied hydrated calcium oxalate and its ions at the restricted Hartree–Fock RHF/6-31G* level of theory. Performing a configurational search seems to improve the fit of the HF/6-31G* level to experimental data. The first solvation shell of calcium oxalate contains 13 water molecules, while the first solvation shell of oxalate ion is formed by 14 water molecules. The first solvation shell of Ca(II) is formed by six water molecules, while the second shell contains five. At 298.15 K, we estimate the asymptotic limits (infinite dilution) of the total standard enthalpies of hydration for Ca(II), oxalate ion and calcium oxalate as ?480.78, –302.78 and –312.73 kcal mol^?1, resp. The dissociation of hydrated calcium oxalate is an endothermic process with an asymptotic limit of +470.84 kcal mol^?1.

46,X,t(Y;Y)(p1I;p1I）合并无精症一例报告

患者男性,28岁。因婚后3年不育而就 诊。患者为头胎足月顺产。其母孕期无有害物 质或放射线接触史,无发烧及病毒感染史,无服 药史。其父母非近亲婚配。家族中无不育或多 发畸形及智力低下者。患者共兄弟3人,其两 个弟弟均已结婚,并有正常生育能力。其妻作 过各项不孕症检查,未见异常。     

原生动物门(Profozoa)(一)

原生动物属于动物界中最原始、最低等的单细胞动物。由于它们的核与细胞质之间存在有明显的核膜,因此这类动物应归属于真核动物。除生活在海洋的放射虫和有孔虫等,原生动物在形态上虽然是一个体形微小(一般在300微米以下)的单细胞动物,但它们又区别于高等动物的体细胞,而是一个完整的,能够独立生活的有机体;它们除具有一般细胞共有的细胞膜、细胞质和细胞核外,还具有一般多细胞动物的运动,消化、呼吸、排泄、生殖和感应性等生理功能。因此,原生动物是一个结构复杂功能奇特的单细胞动物。     

In memoriam: Lauri Saxén (1927-2005)

Dr. Lauri "Tupu" Saxen died last October (2005) at the age of 78. He was a physician, a scientist, a photographer, a naturalist, a great story-teller and a man who enjoyed science enormously. His name has become synonymous with the Finnish school of Developmental Biology, a school that focuses on reciprocal inductive interactions during vertebrate organogenesis. But many biologists probably don't know the full extent of his importance to the field. A few years ago, I had the occasion to outline some of his contributions which are so varied and important that it is difficult to believe that they are the work of one person, and I have included them in this brief eulogy. One could divide his scientific contributions into five categories: (1) the threshold hypothesis of amphibian metamorphosis; (2) the double-gradient hypothesis of primary embryonic induction; (3) the analysis of reciprocal induction during kidney development; (4) the integration of developmental biology with epidemiology and (5) the maintenance of a national infrastructure for science.     

Synthesis and Characterization of a Ditriflate-Bridged, Diiron(II) Complex with Syn-N-Donor Ligands: [Fe(2)(μ-OTf)(2)(PIC(2)DET)(2)](BARF)(2)

The synthesis and characterization of the diiron(II) complex [Fe(2)(μ-OTf)(2)-(PIC(2)DET)(2)](BARF)(2) (2), where PIC(2)DET is a 2,3-diethynyltriptycene-linked dipicolinic methyl ester ligand, are described. The dication in 2, contains, [Fe(2)(μ-OTf)(2)(PIC(2)DET)(2)](2+) two symmetry-equivalent iron atoms with octahedral coordination geometries. Each metal ion has a N(2)O(4) atom donor set that includes four atoms from two picolinic ester N,O chelate rings, as well as two oxygen atoms from the bridging trifluoromethanesulfonate groups. The Fe(2)(μ-OTf)(2) core of 2 is stabilized by two PIC(2)DET ligands that bind the two metal ions in a head-to-head fashion, leading to an Fe···Fe distance of 5.173(1)?. Molar conductivity data for 2 are consistent with Fe(2)(μ-OTf)(2)(PIC(2)DET)(2)](2+) retaining its identity in acetone solutions, where it behaves as a 2:1 electrolyte. (1)H NMR spectroscopic, solution (d(6)-acetone) and solid-state magnetic susceptibility data all indicate that the iron atoms of 2 are high-spin (S = 2). A fit of the magnetic data (2 - 300K) to a spin-only isotropic exchange Hamiltonian H = -2JS(1)·S(2) are consistent with weak antiferromagnetic coupling between the two iron atoms with J ~ -0.99(2) cm(-1) and g = 2.10(1).     

Biosynthesis of (1,3)(1,4)-β-glucan and (1,3)-β-glucan in barley (Hordeum vulgare L.)

Mixed membrane preparations from the coleoptiles and first leaves of young barley (Hordeum vulgare L. cv. Triumph) plants catalysed the synthesis of 55% methanol-insoluble labelled material from UDP[U-¹⁴C]glucose, the main components of which were identified as (1,3)(1,4)-- and (1,3)--D-glucans. The membrane preparations also catalysed the transformation of UDP-glucose into labelled low-molecular-weight products, mainly glucose (by phosphatase action), glucose-1-phosphate (by phosphodiesterase action) and glyco(phospho)lipids (by glycosyltransferase action). The formation of (1,3)(1,4)--glucans, (1,3)--glucans, and the other reactions competing for UDP-glucose, were monitored simultaneously and quantitatively by a novel procedure based on enzymatic analysis, thin-layer chromatography and digital autoradiography. Thus it was possible (i) to optimise conditions to obtain (1,3)(1,4)--glucan synthesis or (1,3)--glucan synthesis in isolation, and (ii) to study the influence of temperature, pH, cofactors, substrate concentration etc. on the (1,3)(1,4) and (1,3)--glucan synthesis reactions even when both occurred together. The synthesis of both -glucans was optimal at 20°C. In Tris-HCl buffer, the pH optima for (1,3)(1,4)--glucan synthesis and (1,3)--glucan synthesis were pH 8.5 and pH 7.0, respectively. Both glucan-synthesis reactions required Mg²⁺: (1,3)--glucan synthesis was optimal at 2 mM, whereas (1,3)(1,4)--glucan synthesis continued to increase up to 200 mM Mg²⁺, when the ion was supplied as the sulphate. (1,3)--Glucan synthesis was Ca²⁺ dependent and this dependence could be abolished by proteinase treatment. The K _m with respect to UDP-glucose was 1.5 mM for (1,3)--glucan synthesis and approximately 1 mM for (1,3)(1,4)--glucan synthesis. The (1,3)(1,4)--glucan formed in vitro had the same ratio of trisaccharide to tetrasaccharide structural blocks irrespective of the experimental conditions used during the synthesis: its enzymatic fragmentation pattern was indistinguishable from that of barley endosperm (1,3)(1,4)--glucan. This indicates either a single synthase enzyme, which is responsible for the formation of both linkage types, or two enzymes which are very tightly coupled functionally.Abbreviations G4G4G3G Glc(1,4)Glc(1,4)Glc(1,3)Glc (-linked) - UDP-Glc uridine-5-diphosphate glucose We are grateful to the Commission of the European Communities for the award of Training Fellowships to Christine Vincent and Martin Becker.     

西藏蕨类植物增补(II)(英文)

报道了 8种蕨类植物为西藏新记录 ,并讨论了西藏蕨类植物的区系特点和分类问题     

生理卫生教学参考资料(下册)(续)

第三节脑本节主要闡述脑的构造和它的机能,从量力性的观点出发,教材仅介紹延髓、小脑和大脑三个部分,这是适合实际情况的。延髓的机能着重的介紹了几个神經中枢的机能——呼吸中枢、心搏中枢、血管舒縮中枢和唾液分泌中枢。这几种中枢的机能在上冊各章部已敍述了一些感性知識,例如講到血的流动时就举出肌肉活动加强时,它里面毛細血管舒张的数目就多一些。这一段內就把这些感性知識提高到理論來認識,进一步加深和巩固反射的概念。同时还为講高級神經活动打下基础。例如唾液分泌中枢的位置等。     

《遗传学原理》(第3版)(中文版)(彩色版)

D.P.Snustad M.J.Simmons等著赵寿元乔守怡等译(复旦大学)书号:978-7-04-017147-1出版日期:2011年4月定价:260.00插图:1000幅字数:180万这是北美较流行的一本优秀的遗传学入门教材。     

Structures and aromaticity of X2Y 2 − (X = C, Si, Ge and Y = N, P, As) anions

The equilibrium geometries, total energies, and vibrational frequencies of anions X₂Y₂ ⁻ (X = C, Si, Ge and Y = N, P, As) are theoretically investigated with density functional theory (DFT) method. Our calculation shows that for C₂N₂ ⁻ species, the D _2h isomer is the most stable four-membered structure, and for other species the C _2v isomer in which two X atoms are contrapuntal is the most stable structure at the B3LYP/6-311 +G_* level. Wiberg bond index (WBI) and negative nucleus-independent chemical shift (NICS) value indicate the existence of delocalization in stable X₂Y₂ ⁻ structures. A detailed molecular orbital (MO) analysis further reveals that stable isomers of these species have strongly aromatic character, which strengthens the structural stability and makes them closely connected with the concept of aromaticity.     

Synthesis and characterization of triaminecobalt(III) complexes and acid hydrolysis kinetics of fac-[Codpt(H2O)nX3−n]n+ (X = Cl,Br; n = 0,1,2)

The complexes CodptX₃ and [Codpt(H₂O)X₂]ClO₄ (X = Cl, Br; dpt = dipropylenetriamine = NH(CH₂CH₂CH₂NH₂)₂) have been prepared and characterized. Rate constants (s⁻¹) for aqueous solution at 25 °C and μ = 0.5 M (NaClO₄), for the acid-independent sequential ractions.

have been measured spectrophotometrically. For X = Cl: k₁ ⋍ 2 × 10⁻², k₂ = 1.7 × 10⁻⁴ and k₃ = 4.8 × 10⁻⁶, and for X = Br: k₁ ⋍ 2 × 10⁻², k₂ = 5.25 × 10⁻⁴ and k₃ = 2.5 × 10⁻⁵ The primary equation was found to be acid independent, while the secondary and tertiary aquations were acid-inhibited reactions. For the second step, the rate of the reaction was given by the rate equation

where C_t is the complex concentration in the aqua-and hydroxodihalo species, k′₂ is the rate constant for the acid-dependent pathway and K_a is the equilibrium constant between the hydroxo and aqua complex ions. The activation parameters were evaluated, for X = Cl: ΔH^≠₂ = 106.3 ± 0.4 kJ mol⁻¹ and ΔS^≠₂ = 40.2 ± 1.7 J K⁻¹ mol⁻, and for X = Br: ΔH^≠₂ = 91.6 ± 0.4 kJ mol⁻¹ and ΔS^≠₂ = 0.4 ± 1.7 J K⁻¹ mol⁻¹. The results are discussed and detailed comparisons of the reactivities of these complexes with other haloaminecobalt(III) species are presented.     

The impact of different chelating leaving groups on the substitution kinetics of mononuclear PtII(1,2- trans - R , R -diaminocyclohexane)(X–Y) complexes

A set of three oxaliplatin derivatives containing 1,2-trans-R,R-diaminocyclohexane (dach) as a spectator ligand and different chelating leaving groups X–Y, viz., [Pt(dach)(O,O-cyclobutane-1,1-dicarboxylate)], or Pt(dach)(CBDCA), [Pt(dach)(N,O-glycine)]⁺, or Pt(dach)(gly), and [Pt(dach)(N,S-methionine)]⁺, or Pt(dach)(l-Met), where l-Met is l-methionine, were synthesized and the crystal structure of Pt(dach)(gly) was determined by X-ray diffraction. The effect of the leaving group on the reactivity of the resulting Pt(II) complexes was studied for the nucleophiles thiourea, glutathione (GSH) and l-Met under pseudo-first-order conditions as a function of nucleophile concentration and temperature, using UV–vis spectrophotometric techniques. ¹H NMR spectroscopy was used to follow the substitution of the leaving group by guanosine 5′-monophosphate (5′-GMP²⁻) under second-order conditions. The rate constants indicate for all reactions a direct substitution of the X–Y chelate by the selected nucleophiles, thereby showing that the nature of the chelate, viz., O–O (CBDCA²⁻), N–O (glycine) or S–N (l-Met), respectively, plays an important role in the kinetic and mechanistic behavior of the Pt(II) complex. The k ₁ values for the reaction with thiourea, l-Met, GSH and 5′-GMP²⁻ were found to be as follows (10³ k ₁, 37.5 °C, M⁻¹ s⁻¹): Pt(dach)(CBDCA) 61 ± 2, 21.6 ± 0.1, 23 ± 1, 0.352 ± 0.002; Pt(dach)(gly) 82 ± 3, 6.2 ± 0.2, 37 ± 1, 1.77 ± 0.01; Pt(dach)(l-Met) (thiourea, GSH) 62 ± 2, 24 ± 1. The activation parameters for all reactions studied suggest an associative substitution mechanism. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

一例原发闭经46,X,psu dic(X)(p22. 3::p22.3)

国外自1974年来,已有等臂双着丝粒X的多种病例报道^[5,6]。我国1982年才开始报道,至今已报道约有6例^[1-3]。现将我室发现一例报告如下。     

Abundance and degree of dispersion of genomic d(GA) n ·d(TC) n sequences

Summary The abundance of d(GA) _n ·d(TC) _n tracts was determined in genomes of rodents and primates. Dot blot hybridization assays revealed that such tracts constitute 0.40%, 0.30%, and 0.40%, respectively, of the rat, hamster, and mouse genomes, but only 0.07% and 0.05% of the human and monkey genomes. A plaque hybridization assay of rat and human genomic libraries showed that 37% and 16%, respectively, of the recombinant phages in these libraries contain d(GA) _n ·d(TC) _n tracts. A survey of sequences stored in the GenBank data bank showed that a significant fraction of the stored rodent genes (about 2.0%) contain long d(GA) _n ·d(TC) _n tracts (n> 30) with <10% mismatching. The primate genes contain only shorter tracts (n<15) with <10% mismatching. In addition, the rodent and the primate genes contain tracts with larger degrees of mismatching. The chicken, which represents an entirely different branch of the evolutionary tree, was found to be as low in d(GA) _n ·d(TC) _n tracts as the primates. It is suggested that a common ancestor of the rodents has acquired the ability to amplify d(GA) _n ·d(TC) _n tracts.     

神经肽Y(NPY)的生理功能研究进展

神经肽Y(NPY)是机体内的一种重要且保守的神经递质,一般以前体形式存在,释放的有活性的NPY主要通过与其受体结合发挥作用。NPY受体包含了亚型Y1、Y2、Y3、Y4、Y5、Y6、Y7、Y8。Y1和Y2是NPY发挥收缩血管作用的关键受体;Y1、Y2和Y5是NPY调节动物摄食行为的关键受体;Y1、Y2和Y4是NPY调控动物焦虑、沮丧行为的必要受体。着重对NPY与其各种受体结合后如何行使动物的相关生理功能的情况进行了阐述。     

Prescott微生物学(第10版)(影印版)

正出版:高等教育出版社出版时间:2018年7月ISBN:978-7-04-049873-8定价:180元内容简介本书原版是国际上最具声誉的微生物学教科书之一,2017年最新版次为第10版。本书秉承《Prescott微生物学》一直以来博大精深、新颖、系统的特点,几乎涵盖了微生物学领域的所有概念,具有一定的深度和广度。全书共9篇43章,既包含学习微生物学的目的、微生物学的化学原理、研究微生物的技术方法、微生物的特