Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18.

Salmonella enterica serovar Typhi (S. typhi) is the aetiological agent of typhoid fever, a serious invasive bacterial disease of humans with an annual global burden of approximately 16 million cases, leading to 600,000 fatalities. Many S. enterica serovars actively invade the mucosal surface of the intestine but are normally contained in healthy individuals by the local immune defence mechanisms. However, S. typhi has evolved the ability to spread to the deeper tissues of humans, including liver, spleen and bone marrow. Here we have sequenced the 4,809,037-base pair (bp) genome of a S. typhi (CT18) that is resistant to multiple drugs, revealing the presence of hundreds of insertions and deletions compared with the Escherichia coli genome, ranging in size from single genes to large islands. Notably, the genome sequence identifies over two hundred pseudogenes, several corresponding to genes that are known to contribute to virulence in Salmonella typhimurium. This genetic degradation may contribute to the human-restricted host range for S. typhi. CT18 harbours a 218,150-bp multiple-drug-resistance incH1 plasmid (pHCM1), and a 106,516-bp cryptic plasmid (pHCM2), which shows recent common ancestry with a virulence plasmid of Yersinia pestis.     

迷向周期和方法在β-簪结构折褶模拟中的应用

采用新近提出的迷向周期和方法（IPS），结合自导Lang evin动态模拟，模拟研究9-余肽折褶成β-箨结构的情况，表明了该结构与NMR观察到的基本一致，而Ewald模拟由于是强烈的镜像相互作用会产生构型偏差，获得致密构型的几率增大，表明IPS方法更适合于周期边界条件的模拟。     

Loss of the SKI proto-oncogene in individuals affected with 1p36 deletion syndrome is predicted by strain-dependent defects in Ski-/- mice.

Experiments involving overexpression of Ski have suggested that this gene is involved in neural tube development and muscle differentiation. In agreement with these findings, Ski-/- mice display a cranial neural tube defect that results in exencephaly and a marked reduction in skeletal muscle mass. Here we show that the penetrance and expressivity of the phenotype changes when the null mutation is backcrossed into the C57BL6/J background, with the principal change involving a switch from a neural tube defect to midline facial clefting. Other defects, including depressed nasal bridge, eye abnormalities, skeletal muscle defects and digit abnormalities, show increased penetrance in the C57BL6/J background. These phenotypes are interesting because they resemble some of the features observed in individuals diagnosed with 1p36 deletion syndrome, a disorder caused by monosomy of the short arm of human chromosome 1p (refs. 6-9). These similarities prompted us to re-examine the chromosomal location of human SKI and to determine whether SKI is included in the deletions of 1p36. We found that human SKI is located at distal 1p36.3 and is deleted in all of the individuals tested so far who have this syndrome. Thus, SKI may contribute to some of the phenotypes common in 1p36 deletion syndrome, and particularly to facial clefting.     

High potassium intake increases the plasma concentration and urinary excretion of vasopressin in the rat

Summary The effect of alterations of dietary potassium intake on the plasma concentration and the urinary excretion of vasopressin was studied in male rats. Ingestion of a high potassium diet resulted in increases in the plasma concentrations of potassium and vasopressin, systolic blood pressure, urine flow, and urinary vasopressin excretion. Ingestion of a low potassium diet had little effect on the plasma vasopressin concentration and systolic blood pressure but caused decreases in the plasma potassium concentration and urinary vasopressin excretion. The results indicate that physiological changes in the plasma potassium concentration or some other consequence of altered dietary potassium intake can affect vasopressin release and excretion.     

Population structure, differential bias and genomic control in a large-scale, case-control association study

The main problems in drawing causal inferences from epidemiological case-control studies are confounding by unmeasured extraneous factors, selection bias and differential misclassification of exposure. In genetics the first of these, in the form of population structure, has dominated recent debate. Population structure explained part of the significant +11.2% inflation of test statistics we observed in an analysis of 6,322 nonsynonymous SNPs in 816 cases of type 1 diabetes and 877 population-based controls from Great Britain. The remainder of the inflation resulted from differential bias in genotype scoring between case and control DNA samples, which originated from two laboratories, causing false-positive associations. To avoid excluding SNPs and losing valuable information, we extended the genomic control method by applying a variable downweighting to each SNP.     

Significance of cyclic AMP in the regulation of exocrine pancreas secretion

Zusammenfassung Nachweis, dass die Zufuhr von dibutyryl-zyklischem AMP (DcAMP) in vitro die Enzymproduktion erhöht und zwar mit nur geringer Gewichtsveränderung des Kaninchenpankreas. Die Enzymproduktion wird ebenso durch Theophyllin vermehrt und es wird vermutet, das DcAMP der Vermittler der pankreozymen Wirkung im Kaninchen ist.     

The climatic changes of the past thousand years

Résumé Exposé des données historiques et naturelles attestant des fluctuations de climat dans l'hémisphère nord au cours du dernier millénaire. Dans la zone tempérée, il y eut depuis les environs de l'an 1000 cinq époques climatiques: 1° 1000–1250, climat doux et sec. 2° 1250–1400, pluvieux et orageux. 3° 1400–1600 plus froid, moins orageux. 4° 1600–1850, avance des glaciers. 5° réchauffement progressif. Les causes de ces changements sont discutées à la fin de l'article.