Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms.

The stable propagation of genetic information requires that the entire genome of an organism be faithfully replicated once and only once each cell cycle. In eukaryotes, this replication is initiated at hundreds to thousands of replication origins distributed over the genome, each of which must be prohibited from re-initiating DNA replication within every cell cycle. How cells prevent re-initiation has been a long-standing question in cell biology. In several eukaryotes, cyclin-dependent kinases (CDKs) have been implicated in promoting the block to re-initiation, but exactly how they perform this function is unclear. Here we show that B-type CDKs in Saccharomyces cerevisiae prevent re-initiation through multiple overlapping mechanisms, including phosphorylation of the origin recognition complex (ORC), downregulation of Cdc6 activity, and nuclear exclusion of the Mcm2-7 complex. Only when all three inhibitory pathways are disrupted do origins re-initiate DNA replication in G2/M cells. These studies show that each of these three independent mechanisms of regulation is functionally important.     

A radiation hybrid map of mouse genes

A comprehensive gene-based map of a genome is a powerful tool for genetic studies and is especially useful for the positional cloning and positional candidate approaches. The availability of gene maps for multiple organisms provides the foundation for detailed conserved-orthology maps showing the correspondence between conserved genomic segments. These maps make it possible to use cross-species information in gene hunts and shed light on the evolutionary forces that shape the genome. Here we report a radiation hybrid map of mouse genes, a combined project of the Whitehead Institute/Massachusetts Institute of Technology Center for Genome Research, the Medical Research Council UK Mouse Genome Centre, and the National Center for Biotechnology Information. The map contains 11,109 genes, screened against the T31 RH panel and positioned relative to a reference map containing 2,280 mouse genetic markers. It includes 3,658 genes homologous to the human genome sequence and provides a framework for overlaying the human genome sequence to the mouse and for sequencing the mouse genome.     

有限单元法 并行稀疏静力学和本征值求解

有限单元法（FEM）及其软件是求解大型工程应用的最有效工具之一。在这类应用问题中，有效的方程和本征值求解器扮演着至关重要的角色。稀疏矩阵及其求解技术已经足够成熟并在商用软件中实现。然而，截至目前，关于稀疏系数方程求解、Lanczos域分解或FEM并行计算的详细介绍的书籍尚不多见。     

Radiation hybrid map of the mouse genome.

Radiation hybrid (RH) maps are a useful tool for genome analysis, providing a direct method for localizing genes and anchoring physical maps and genomic sequence along chromosomes. The construction of a comprehensive RH map for the human genome has resulted in gene maps reflecting the location of more than 30,000 human genes. Here we report the first comprehensive RH map of the mouse genome. The map contains 2,486 loci screened against an RH panel of 93 cell lines. Most loci (93%) are simple sequence length polymorphisms (SSLPs) taken from the mouse genetic map, thereby providing direct integration between these two key maps. We performed RH mapping by a new and efficient approach in which we replaced traditional gel- or hybridization-based assays by a homogeneous 5'-nuclease assays involving a single common probe for all genetic markers. The map provides essentially complete connectivity and coverage across the genome, and good resolution for ordering loci, with 1 centiRay (cR) corresponding to an average of approximately 100 kb. The RH map, together with an accompanying World-Wide Web server, makes it possible for any investigator to rapidly localize sequences in the mouse genome. Together with the previously constructed genetic map and a YAC-based physical map reported in a companion paper, the fundamental maps required for mouse genomics are now available.     

Generation and annotation of the DNA sequences of human chromosomes 2 and 4

Human chromosome 2 is unique to the human lineage in being the product of a head-to-head fusion of two intermediate-sized ancestral chromosomes. Chromosome 4 has received attention primarily related to the search for the Huntington's disease gene, but also for genes associated with Wolf-Hirschhorn syndrome, polycystic kidney disease and a form of muscular dystrophy. Here we present approximately 237 million base pairs of sequence for chromosome 2, and 186 million base pairs for chromosome 4, representing more than 99.6% of their euchromatic sequences. Our initial analyses have identified 1,346 protein-coding genes and 1,239 pseudogenes on chromosome 2, and 796 protein-coding genes and 778 pseudogenes on chromosome 4. Extensive analyses confirm the underlying construction of the sequence, and expand our understanding of the structure and evolution of mammalian chromosomes, including gene deserts, segmental duplications and highly variant regions.     

Paradoxical inhibition of the effects of bradykinin by some sulfhydryl reagents

Résumé Plusieurs dérivés thiol et deux antioxidants inhibent la bronchoconstriction chez le cobaye, une partie de l'hypotension chez le lapin et la libération de «rabbit aorta contracting substance» (RCS) dues à la bradykinine Il est proposé que les effets communs à la bradykinine, à la SRS-A, SRS-C et à l'acide arachidonique, qui sont bloqués par des antiinflammatoires, acides, et par les dérivés thiol, sont dus à la formation de RCS, constituée par des péroxydes cicliques analogues aux précurseurs instables des prostaglandines E 2 et F 2 alpha.

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We thank MrsB. Charpentier andC. Bellevrat for technical help, Prof.H. Clauser andJ. R. Vane and DrH. O. J. Collier for comments and DrS. H. Ferreira for advice concerning the superfusion technique and for BPP9. Squibb provided BPP5. This work is part of a thesis leading to the degree of Docteur-ès-Sciences, Orsay (B.B.V.).     

The suppression of star formation by powerful active galactic nuclei

The old, red stars that constitute the bulges of galaxies, and the massive black holes at their centres, are the relics of a period in cosmic history when galaxies formed stars at remarkable rates and active galactic nuclei (AGN) shone brightly as a result of accretion onto black holes. It is widely suspected, but unproved, that the tight correlation between the mass of the black hole and the mass of the stellar bulge results from the AGN quenching the surrounding star formation as it approaches its peak luminosity. X-rays trace emission from AGN unambiguously, whereas powerful star-forming galaxies are usually dust-obscured and are brightest at infrared and submillimetre wavelengths. Here we report submillimetre and X-ray observations that show that rapid star formation was common in the host galaxies of AGN when the Universe was 2-6 billion years old, but that the most vigorous star formation is not observed around black holes above an X-ray luminosity of 10(44) ergs per second. This suppression of star formation in the host galaxy of a powerful AGN is a key prediction of models in which the AGN drives an outflow, expelling the interstellar medium of its host and transforming the galaxy's properties in a brief period of cosmic time.     

抛体运动的轨迹长度与所围面积研究

空气阻力对抛体的运动可以产生显著的影响.运用近似的方法处理超越方程,给出了考虑空气阻力时抛体运动轨迹的长度和轨迹所包围的面积的近似解析解.数值计算表明：（1）当kt/m越小时轨迹长度与所围面积的近似解析解与真实值越接近;（2）抛体运动轨迹的长度取最大值时,抛射角随空气阻力系数的增大而减小：（3）抛体运动轨迹所围面积取最大值时,抛射角随空气阻力系数的增大而增加.