Intense and highly localized gene conversion activity in human meiotic crossover hot spots

Meiotic gene conversion has an important role in allele diversification and in the homogenization of gene and other repeat DNA sequence families, sometimes with pathological consequences. But little is known about the dynamics of gene conversion in humans and its relationship to meiotic crossover. We therefore developed screening and selection methods to characterize sperm conversions in two meiotic crossover hot spots in the major histocompatibility complex (MHC) and one in the sex chromosomal pseudoautosomal pairing region PAR1 (ref. 9). All three hot spots are active in gene conversion and crossover. Conversion tracts are short and define a steep bidirectional gradient centered at the peak of crossover activity, consistent with crossovers and conversions being produced by the same recombination-initiating events. These initiations seem to be spread over a narrow zone, rather than occurring at a single site, and seem preferentially to yield conversions rather than crossovers. Crossover breakpoints are more broadly diffused than conversion breakpoints, suggesting either differences between conversion and crossover processing after initiation or the existence of a quality control checkpoint at which short interactions between homologous chromosomes are preferentially aborted as conversions.     

The effect of thermal injury on plasma carnitine in rats

Summary The plasma concentration of L-carnitine in scalded rats was determined to be greater (p0.05) than that of control rats at 6 h following the administration of a 20% body surface, full-thickness burn produced by scalding in a 100°C water bath for 15 sec.     

Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24

Using a multistage genetic association approach comprising 7,480 affected individuals and 7,779 controls, we identified markers in chromosomal region 8q24 associated with colorectal cancer. In stage 1, we genotyped 99,632 SNPs in 1,257 affected individuals and 1,336 controls from Ontario. In stages 2-4, we performed serial replication studies using 4,024 affected individuals and 4,042 controls from Seattle, Newfoundland and Scotland. We identified one locus on chromosome 8q24 and another on 9p24 having combined odds ratios (OR) for stages 1-4 of 1.18 (trend; P = 1.41 x 10(-8)) and 1.14 (trend; P = 1.32 x 10(-5)), respectively. Additional analyses in 2,199 affected individuals and 2,401 controls from France and Europe supported the association at the 8q24 locus (OR = 1.16, trend; 95% confidence interval (c.i.): 1.07-1.26; P = 5.05 x 10(-4)). A summary across all seven studies at the 8q24 locus was highly significant (OR = 1.17, c.i.: 1.12-1.23; P = 3.16 x 10(-11)). This locus has also been implicated in prostate cancer.     

Fullerenes from aromatic precursors by surface-catalysed cyclodehydrogenation

Graphite vaporization provides an uncontrolled yet efficient means of producing fullerene molecules. However, some fullerene derivatives or unusual fullerene species might only be accessible through rational and controlled synthesis methods. Recently, such an approach has been used to produce isolable amounts of the fullerene C(60) from commercially available starting materials. But the overall process required 11 steps to generate a suitable polycyclic aromatic precursor molecule, which was then dehydrogenated in the gas phase with a yield of only about one per cent. Here we report the formation of C(60) and the triazafullerene C(57)N(3) from aromatic precursors using a highly efficient surface-catalysed cyclodehydrogenation process. We find that after deposition onto a platinum (111) surface and heating to 750 K, the precursors are transformed into the corresponding fullerene and triazafullerene molecules with about 100 per cent yield. We expect that this approach will allow the production of a range of other fullerenes and heterofullerenes, once suitable precursors are available. Also, if the process is carried out in an atmosphere containing guest species, it might even allow the encapsulation of atoms or small molecules to form endohedral fullerenes.     

Microdeletion encompassing MAPT at chromosome 17q21.3 is associated with developmental delay and learning disability

Recently, the application of array-based comparative genomic hybridization (array CGH) has improved rates of detection of chromosomal imbalances in individuals with mental retardation and dysmorphic features. Here, we describe three individuals with learning disability and a heterozygous deletion at chromosome 17q21.3, detected in each case by array CGH. FISH analysis demonstrated that the deletions occurred as de novo events in each individual and were between 500 kb and 650 kb in size. A recently described 900-kb inversion that suppresses recombination between ancestral H1 and H2 haplotypes encompasses the deletion. We show that, in each trio, the parent of origin of the deleted chromosome 17 carries at least one H2 chromosome. This region of 17q21.3 shows complex genomic architecture with well-described low-copy repeats (LCRs). The orientation of LCRs flanking the deleted segment in inversion heterozygotes is likely to facilitate the generation of this microdeletion by means of non-allelic homologous recombination.     

Axonal loss and neuroinflammation caused by peroxisome-deficient oligodendrocytes

Oligodendrocytes myelinate axons for rapid impulse conduction and contribute to normal axonal functions in the central nervous system. In multiple sclerosis, demyelination is caused by autoimmune attacks, but the role of oligodendroglial cells in disease progression and axon degeneration is unclear. Here we show that oligodendrocytes harbor peroxisomes whose function is essential for maintaining white matter tracts throughout adult life. By selectively inactivating the import factor PEX5 in myelinating glia, we generated mutant mice that developed normally, but within several months showed ataxia, tremor and premature death. Absence of functional peroxisomes from oligodendrocytes caused widespread axonal degeneration and progressive subcortical demyelination, but did not interfere with glial survival. Moreover, it caused a strong proinflammatory milieu and, unexpectedly, the infiltration of B and activated CD8+ T cells into brain lesions. We conclude that peroxisomes provide oligodendrocytes with an essential neuroprotective function against axon degeneration and neuroinflammation, which is relevant for human demyelinating diseases.     

电信项目管理

本书是一本涵盖项目管理领域的精简丛书。作者用通俗的语言为工作在电信网中的项目经理讲述了许多关键的概念。本书不仅完全符合项目管理学院（PMI）推荐的管理过程，而且对于管理流程在电信项目中的应用进行了扩展。本书包括了应用于电信网相关领域的一些概念、应用，同时介绍了用于项目计划、组织、回溯和管理的工具。书中提供了许多有线和无线运营商项目的实际例子来充分解释项目管理学概念，还对跨部门问的项目合作提出了指导意见。