重元素:一次非常短暂的邂逅

人们对于元素周期表边缘范围的重元素知之甚少。然而人们如何研究在瞬间就衰变的子原呢?肯德尔·鲍威尔(Kendall Powell)找到了解决方法。     

Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11

The microtubule-associated protein tau (encoded by MAPT) and several tau kinases have been implicated in neurodegeneration, but only MAPT has a proven role in disease. We identified mutations in the gene encoding tau tubulin kinase 2 (TTBK2) as the cause of spinocerebellar ataxia type 11. Affected brain tissue showed substantial cerebellar degeneration and tau deposition. These data suggest that TTBK2 is important in the tau cascade and in spinocerebellar degeneration.     

Recombination and linkage disequilibrium in Arabidopsis thaliana

Linkage disequilibrium (LD) is a major aspect of the organization of genetic variation in natural populations. Here we describe the genome-wide pattern of LD in a sample of 19 Arabidopsis thaliana accessions using 341,602 non-singleton SNPs. LD decays within 10 kb on average, considerably faster than previously estimated. Tag SNP selection algorithms and 'hide-the-SNP' simulations suggest that genome-wide association mapping will require only 40%-50% of the observed SNPs, a reduction similar to estimates in a sample of African Americans. An Affymetrix genotyping array containing 250,000 SNPs has been designed based on these results; we demonstrate that it should have more than adequate coverage for genome-wide association mapping. The extent of LD is highly variable, and we find clear evidence of recombination hotspots, which seem to occur preferentially in intergenic regions. LD also reflects the action of selection, and it is more extensive between nonsynonymous polymorphisms than between synonymous polymorphisms.     

Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.     

Receiving mixed signals: uncoupling oligodendrocyte differentiation and myelination

The development and maturation of an oligodendroglial cell is comprised of three intimately related processes that include proliferation, differentiation, and myelination. Here we review how proliferation and differentiation are controlled by distinct molecular mechanisms and discuss whether differentiation is merely a default of inhibited proliferation. We then address whether differentiation and myelination can be uncoupled in a similar manner. This task is particularly challenging because an oligodendrocyte cannot myelinate without first differentiating, and these processes are therefore not mutually exclusive. Is it solely the presence of the axon that distinguishes a differentiated oligodendrocyte from a myelinating one? Uncoupling these two processes requires identifying specific signals that regulate myelination without affecting the differentiation process. We will review current understanding of the relationship between differentiation and myelination and discuss whether these two processes can truly be uncoupled.     

The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease

The recycling of the amyloid precursor protein (APP) from the cell surface via the endocytic pathways plays a key role in the generation of amyloid beta peptide (Abeta) in Alzheimer disease. We report here that inherited variants in the SORL1 neuronal sorting receptor are associated with late-onset Alzheimer disease. These variants, which occur in at least two different clusters of intronic sequences within the SORL1 gene (also known as LR11 or SORLA) may regulate tissue-specific expression of SORL1. We also show that SORL1 directs trafficking of APP into recycling pathways and that when SORL1 is underexpressed, APP is sorted into Abeta-generating compartments. These data suggest that inherited or acquired changes in SORL1 expression or function are mechanistically involved in causing Alzheimer disease.     

Accurate forecasting of the undecided population in a public opinion poll

The problem of pollsters is addressed which is to forecast accurately the final answers of the undecided respondents to the primary question in a public opinion poll. The task is viewed as a pattern‐recognition problem of correlating the answers of the respondents to the peripheral questions in the survey with their primary answers. The underlying pattern is determined with a supervised artificial neural network that is trained using the peripheral answers of the decided respondents whose primary answers are also known. With peripheral answers as inputs, the trained network outputs the most probable primary response of an undecided respondent. For a poll conducted to determine the approval rating of the (former) Philippine president, J. E. Estrada in December 1999 and March 2000, the trained network predicted with a 95% success rate the direct responses of a test population that consists of 24.57% of the decided population who were excluded in the network training set. For the undecided population (22.67% of December respondents; 23.67% of March respondents), the network predicted a final response distribution that is consistent with the approval/disapproval ratio of the decided population. Copyright © 2002 John Wiley & Sons, Ltd.     

Experimental immunity against trypanosomiasis

Summary 9 groups of 6 female rats were used in an experiment using fraction 3 ofTrypanosoma rhodesiense. 500 g gave 100% immunoprotection and 1000 and 1500 g gave 66% immunoprotection when challenged with 5×10² T. brucei. 2 groups of 10 female rats were tested for a short period inoculation immune response. In this, 750 g of fraction 3 ofT. rhodesiense gave 70% immunoprotection when challenged withT. brucei.I thank the University of Zambia for support; Dr M. A. Q. Awan, Mazabuka, Zambia, forT. rhodesiense andT. brucei; Prof. J. W. Kibukamusoke, Dr O. Okong'o and Dr W. W. Anokbonggo for advice; Mr L. Nyaliti for technical help.