Mobile DNA elements: controlling transposition with ATP-dependent molecular switches

Nucleotide-binding proteins are often used as molecular switches to control the assembly or activity of macromolecular machines. Recent work has revealed that such molecular switches also regulate the spread of some mobile DNA elements. Bacteriophage Mu and the bacterial transposon Tn7 each use an ATP-dependent molecular switch to select a new site for insertion and to coordinate the assembly of the transposition machinery at that site. Strong parallels between these ATP-dependent transposition proteins and other well-characterized molecular switches, such as Ras and EF-Tu, have emerged.     

Synthetic, biofunctional nucleic acid-based molecular devices

Structural DNA nanotechnology seeks to create architectures of highly precise dimensions using the physical property that short lengths of DNA behave as rigid rods and the chemical property of Watson-Crick base-pairing that acts as a specific molecular glue with which such rigid rods may be joined. Thus DNA has been used as a molecular scale construction material to make molecular devices that can be broadly classified under two categories (i) rigid scaffolds and (ii) switchable architectures. This review details the growing impact of such synthetic nucleic acid based molecular devices in biology and biotechnology. Notably, a significant trend is emerging that integrates morphology-rich nucleic acid motifs and alternative molecular glues into DNA and RNA architectures to achieve biological functionality.     

Molecular evolution: dynamic combinatorial libraries, autocatalytic networks and the quest for molecular function

The principles of Darwinian evolution have been explored in molecular systems such as autocatalytic networks and dynamic combinatorial libraries. Molecular evolution in such systems manifests itself as ligand or receptor amplification by selection. Research efforts exploring these concepts may provide a mechanism for the identification of novel catalysts, molecular receptors and bioactive molecules.     

空间分子生态学——分子生态学与空间生态学相结合的新领域

分子标记、基因流、种群空间动态是当前生命科学研究中的热点领域。RFLPs、RAPDs、微卫星等新的分子标记的不断涌现,促进了这些领域的飞速发展。对种群空间动态研究中的等级岛屿模型、距离隔离模型、脚踏石模型、集合种群模型等方面许多令人瞩目的进展做了介绍。同时还介绍了遗传距离、基因流及其测度、基因突变模型、3S技术、空间精确性种群模型和基因频率的空间自相关等热点领域。最后,就空间分子生态学存在的问题与前景进行了讨论,指出了空间分子生态学可能的发展方向。     

Characterization of a protein recognizing minor groove binders-damaged DNA.

By using electromobility shift assay (EMSA), we have identified a protein able to recognize the DNA only if it was previously reacted with minor groove binders. This protein binds with very high affinity AT containing DNA treated with minor groove binders such as distamycin A, Hoechst 33258 and 33342, CC-1065 and ethidium bromide minor groove intercalator, but not with major groove binders such as quinacrine mustard, cisplatin or melphalan, or with topoisomerase I inhibitor camptothecin or topoisomerase II inhibitor doxorubicin. This protein was found to be present in different extracts of human, murine and hamster cells, with the human protein which appears to have a molecular weight slightly lower than that of the other species. This protein was found to be expressed both in cancer and normal tissues. By using molecular ultrafiltration techniques as well as southwestern analysis it was estimated that the apparent molecular weight is close to 100 kDa. We can exclude an identity between this protein and other proteins, with a similar molecular weight previously reported to be involved in DNA damage recognition/repair, such as topoisomerase I, mismatch repair activities such as the prokaryotic MutS protein and its human homologue hMSH2 or proteins of the nucleotide excision repair system such as ERCC1, -2, -3 and -4.     

Emergence of airway smooth muscle functions related to structural malleability

The function of a complex system such as a smooth muscle cell is the result of the active interaction among molecules and molecular aggregates. Emergent macroscopic manifestations of these molecular interactions, such as the length-force relationship and its associated length adaptation, are well documented, but the molecular constituents and organization that give rise to these emergent muscle behaviors remain largely unknown. In this minireview, we describe emergent properties of airway smooth muscle that seem to have originated from inherent fragility of the cellular structures, which has been increasingly recognized as a unique and important smooth muscle attribute. We also describe molecular interactions (based on direct and indirect evidence) that may confer malleability on fragile structural elements that in turn may allow the muscle to adapt to large and frequent changes in cell dimensions. Understanding how smooth muscle works may hinge on how well we can relate molecular events to its emergent macroscopic functions.     

The genome as a life-history character: why rate of molecular evolution varies between mammal species

DNA sequences evolve at different rates in different species. This rate variation has been most closely examined in mammals, revealing a large number of characteristics that can shape the rate of molecular evolution. Many of these traits are part of the mammalian life-history continuum: species with small body size, rapid generation turnover, high fecundity and short lifespans tend to have faster rates of molecular evolution. In addition, rate of molecular evolution in mammals might be influenced by behaviour (such as mating system), ecological factors (such as range restriction) and evolutionary history (such as diversification rate). I discuss the evidence for these patterns of rate variation, and the possible explanations of these correlations. I also consider the impact of these systematic patterns of rate variation on the reliability of the molecular date estimates that have been used to suggest a Cretaceous radiation of modern mammals, before the final extinction of the dinosaurs.     

肿瘤的分子治疗新进展

肿瘤的发生、发展是一个多步骤、多基因参与的、复杂的系统性过程.分子治疗作为21世纪最有希望根治人类肿瘤的技术,其治疗技术的关键在于靶分子的选择,寻找合适的靶分子一直是分子治疗肿瘤的重要方向.针对近年来肿瘤治疗研究中发现的端粒酶靶标、抗血管生成基因靶标、apoptin、survivin、stathmin、autophagy、PUMA、转铁蛋白受体靶标和相应的治疗策略作一综述.     

Bacterial evolution and silicon

This review examines the possible role of silicon in molecular evolution. It is possible silicon participated in early molecular evolution by providing a stable mineral surface or gel structure where the assembly and replication of primitive genetic information occurred. However, as molecular evolution proceeded, silicon was not required in the evolution of C-based organisms. Silicon can be accumulated by diatoms and other living organisms such as silicoflagellates, some xanthophytes, radiolarians and actinopods and plants such as grasses, ferns, horseradish, some trees and flowers, some sponges, insects and invertebrates and bacteria and fungi. Silicon also has a role in synthesis of DNA, DNA polymerase and thymidylate kinase activity in diatoms. It is not unreasonable to examine the role of silicon in early molecular evolution as it may have been part of a micro-environment in which assembly of genetic information occurred.     

Cytogenetic and molecular abnormalities in myelodysplastic syndrome

Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematological disorders characterized by ineffective hematopoiesis which causes peripheral cytopenias and a risk of progression to acute myeloid leukemia. Although various forms of chromosomal abnormalities have been detected in approximately 50-60% of patients with de novo MDS and in up to 80% of patients with therapy-related MDS, their molecular significance for pathogenesis and disease progression is not yet fully understood. Recent technical advances in molecular biology have disclosed more accurately details of pathological chromosomal and molecular aberrations in MDS. Such details could not be identified with conventional cytogenetical techniques, including G-banding. In particular, with recent technical advances in comparative genome hybridization or single nucleotide polymorphism array technology, several candidate genes for the pathogenesis of MDS have been identified, which are located in minimally deleted or uniparental disomy segments. Moreover, epigenetic deregulation of gene expression is also likely to be involved in the pathogenesis of MDS. Accordingly, in addition to classical oncogenic abnormalities, such as p53 abnormalities, or NRAS mutation, various molecular abnormalities, such as TET2, RPS14, or c-CBL, have been identified and/or proposed as the novel candidates for molecular basis of the development and progression of MDS. A better understanding of the causative molecular events underlying MDS pathogenesis is essential for the development and establishment of a more effective treatment resulting in a complete cure for MDS. We here review current knowledge regarding the molecular significance of chromosomal and genetic aberrations in MDS and the proposed molecular mechanisms of action of new agents for MDS, such as lenalidomide or azacitidine.     

Structural information about organized cholesterol domains from specific antibody recognition

Cholesterol-rich domains have been observed to exist in cell membranes under physiological and pathological conditions. Their compositions and the microenvironment of their formation vary over a wide range. Very little information is however available on the molecular structure and organization of these domains. The techniques available to provide such structural information are reviewed here first. The possibility of using tailor-made antibodies as reporters of molecular organization in membranes is then considered. The concept of antibodies recognizing molecular organization rather than single molecular epitopes is established, reviewing the existing works on antibody and protein recognition of crystalline molecular arrays. The information that such antibodies could provide in cells is finally examined together with a proof of application.     

Diffusion-ordered NMR spectroscopy: a versatile tool for the molecular weight determination of uncharged polysaccharides

Diffusion-ordered NMR spectroscopy (DOSY) experiments have been carried out on dilute aqueous solutions of uncharged saccharide systems and, in particular, on six well characterized pullulan fractions of different molecular weights. The values of diffusion coefficients and hydrodynamic radii determined for the pullulan fractions are in good agreement with the results obtained with other methodologies such as light scattering. Fitting the diffusion coefficients data as a function of the molecular weight allows for the determination of a calibration curve that can be applied to a wide range of mono-, oligo-, and polysaccharides. Therefore, DOSY is proposed as a versatile tool for achieving a simple estimation of the molecular weight of uncharged polysaccharides. Mixtures of homopolymers of different molecular weight can be nicely separated. An advantage of the method is that the same sample used for the NMR characterization can be used for the molecular weight determination without any further manipulation. Other water soluble polymers, such as poly(ethylene oxide) and poly(vinylpyrrolidone), can be roughly characterized using the same calibration curve.     

Structural information about organized cholesterol domains from specific antibody recognition

Cholesterol-rich domains have been observed to exist in cell membranes under physiological and pathological conditions. Their compositions and the microenvironment of their formation vary over a wide range. Very little information is however available on the molecular structure and organization of these domains. The techniques available to provide such structural information are reviewed here first. The possibility of using tailor-made antibodies as reporters of molecular organization in membranes is then considered. The concept of antibodies recognizing molecular organization rather than single molecular epitopes is established, reviewing the existing works on antibody and protein recognition of crystalline molecular arrays. The information that such antibodies could provide in cells is finally examined together with a proof of application.     

Protein Molecular Surface Mapped at Different Geometrical Resolutions

Many areas of biochemistry and molecular biology, both fundamental and applications-orientated, require an accurate construction, representation and understanding of the protein molecular surface and its interaction with other, usually small, molecules. There are however many situations when the protein molecular surface gets in physical contact with larger objects, either biological, such as membranes, or artificial, such as nanoparticles. The contribution presents a methodology for describing and quantifying the molecular properties of proteins, by geometrical and physico-chemical mapping of the molecular surfaces, with several analytical relationships being proposed for molecular surface properties. The relevance of the molecular surface-derived properties has been demonstrated through the calculation of the statistical strength of the prediction of protein adsorption. It is expected that the extension of this methodology to other phenomena involving proteins near solid surfaces, in particular the protein interaction with nanoparticles, will result in important benefits in the understanding and design of protein-specific solid surfaces.     

Toward molecular electronics. Self-screening of molecular wires

One-dimensional polyelectrolytes are proposed as molecular devices based on soliton propagation. The use of such "molecular wires" as delay lines or shift registers raises the problem of their electrical screening, because, when a large number of these wires are densely packed, cross-talking between them might occur. In order to overcome such a drawback, a detailed study of the polyelectrolyte behavior in an ionic solution has been developed, under equilibrium conditions. The results bring into evidence a condensation process, around each molecular wire, of the mobile ions in the solution. The consequent self-screening effect could be relevant in reducing cross-talking.     

植物功能基因组研究中出现的新型分子标记

随着功能基因组学的发展,表达序列标签(Expressed Sequence Tags, ESTs)已经成为开发以PCR为基础的新型分子标记的重要资源。本文综述了植物功能基因组研究中出现的EST-SSR、CAPS、SNP、SRAP和TRAP等新型分子标记的基本原理和特点。这些标记具有其显著的优势,如开发简便、信息量高和通用性好等,尤其是由于它们来源于基因编码区（ORFs),因此具有很高的物种间通用性,并且其多态性与基因功能变异相关联。目前,这些功能基因分子标记已广泛应用于遗传图谱构建、重要性状基因定位、比较作图、遗传多样性和品种鉴别、分子标记辅助选择育种等研究中。在文章最后简要介绍了作者所在实验室近年来所开展的功能基因分子标记工作,并说明了在使用这些功能基因分子标记时可能会出现的问题。     

Toward molecular electronics

One-dimensional polyelectrolytes are proposed as molecular devices based on soliton propagation. The use of such “molecular wires” as delay lines or shift registers raises the problem of their electrical screening, because, when a large number of these wires are densely packed, cross-talking between them might occur. In order to overcome such a drawback, a detailed study of the polyelectrolyte behavior in an ionic solution has been developed, under equilibrium conditions. The results bring into evidence a condensation process, around each molecular wire, of the mobile ions in the solution. The consequent self-screening effect could be relevant in reducing cross-talking.     

A kinesin medley: biochemical and functional heterogeneity

Over the past decade, a remarkable number and diversity of molecular motors have been described in eukaryotic cells. In addition to the identification of novel forms of myosin and dynein, the kinesins have been defined as an entirely new family of molecular motors. There may be as many as 30 different genes in a single organism encoding members of the kinesin superfamily. Why is such diversity in molecular motors needed? The biochemical and functional diversity of the originally defined form of kinesin provides some insights into the roles of molecular motors in cellular dynamics.     

New method for analyzing the molecular weights of proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis

Previously the method for determining protein molecular weights from SDS-PAGE depended on the accidental, only partial linearity of protein movement with the logarithm of its molecular weight. A new, mathematically rigorous method with supporting data is now described demonstrating that such movement is dependent upon the reciprocal of protein size. Experimental data, therefore, follow most closely a hyperbolic curve when plotted directly; it becomes linear and passes through the origin when movement is plotted vs the reciprocal of protein molecular weight. In the earlier method determination of the error of a measurement of molecular weight is very complex and never determined. In the method presented here such error is easily estimated and it is identical in both the hyperbolic and linear forms of data presentation. This method may eventually also allow other less-significant forces controlling movement such as protein charge to be analyzed and understood.