The Helicobacter pylori Genome Project : insights into H. pylori population structure from analysis of a worldwide collection of complete genomes

Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics

Alcohol-metabolizing enzyme gene polymorphisms and alcohol chronic pancreatitis among Polish individuals

Background and aims. Chronic pancreatitis develops in 5–10% of alcohol addicts. In developed societies, alcohol is the cause of chronic pancreatitis in at least 70–80% of cases. The genetic polymorphism of enzymes involved in alcohol metabolism is relevant in the etiopathogenesis of chronic pancreatitis. The aim of the study was to find the ADH, ALDH2 and CYP2E1 alleles and genotypes in the Polish population that are likely to be responsible for higher susceptibility to chronic alcohol pancreatitis. Material and methods. We determined the allele and genotype of ADH2, ADH3, ALDH2 and CYP2E1 in 141 subjects: 44 with alcohol chronic pancreatitis (ACP), 43 healthy alcoholics and 54 healthy non-drinkers as the controls. Genotyping was performed using PCR-RELP methods on white cell DNA. Results. ADH2*1, ADH3*1 alleles and ADH2*1/*1, ADH3*1/*1 genotypes were statistically more frequent among the patients with ACP than among the controls. The ADH3*2/*2 genotype was more frequent among “healthy alcoholics” and in the controls than among those with ACP. In the studied group, only the ALDH2*1 allele was detected, all patients were ALDH2*1/*1 homozygotic. Differences in the CYP2E1 allele and genotype distribution in the examined groups were not significant. Conclusion. In the Polish population examined, ADH3*1 and ADH2*1 alleles may be risk factors for the development of alcoholism. The ADH3*2/*2 genotype may confer protection against ACP. CYP2E1 gene polymorphism is not related to alcoholism and ACP. The Polish population examined is ALDH2*1/*1 homozygotic

Arabidopsis thaliana proliferating cell nuclear antigen has several potential sumoylation sites

Proliferating cell nuclear antigen (PCNA) is post-translationally modified in yeast and animal cells. Major studies carried out in the last decade have focused on the role of sumoylated and ubiquitinated PCNA. Using different approaches, an interaction between plant PCNA and SUMO both in vivo and in bacteria has been demonstrated for the first time. In addition, identical sumoylation patterns for both AtPCNA1 and 2 were observed in bacteria. The plant PCNA sumoylation pattern has been shown to differ significantly from that of Saccharomyces cerevisiae. This result contrasts with a common opinion based on previous structural analysis of yeast, human, and plant PCNAs, which treats PCNA as a highly conserved protein even between species. Analyses of AtPCNA post-translational modifications using different SUMO proteins (SUMO1, 2, 3, and 5) revealed similar modification patterns for each tested SUMO protein. Potential target lysine residues that might be sumoylated in vivo were identified on the basis of in bacteria AtPCNA mutational analyses. Taken together, these results clearly show that plant PCNA is post-translationally modified in bacteria and may be sumoylated in a plant cell at various sites. These data open up important new perspectives for further detailed studies on the role of PCNA sumoylation in plant cells

Left ventricle structural remodelling in the prediabetic Goto-Kakizaki rat

This study tested the hypothesis that experimental prediabetes can elicit structural remodelling in the left ventricle (LV). Left ventricles isolated from 8-week-old male Goto–Kakizaki (GK) rats and age-matched male Wistar control rats were used to assess remodelling changes and underlying transforming growth factor β1 (TGFβ1) activity, prohypertrophic Akt–p70S6K1 signalling and gene expression profile of the extracellular matrix (ECM) using histological, immunohistochemical, immunoblotting and quantitative gene expression analyses. Prediabetes in GK rats was confirmed by impaired glucose tolerance and modestly elevated fasting blood glucose. Left ventricle remodelling in the GK rat presented with marked hypertrophy of cardiomyocytes and increased ECM deposition that together translated into increased heart size in the absence of ultrastructural changes or fibre disarray. Molecular derangements underlying this phenotype included recapitulation of the fetal gene phenotype markers B-type natriuretic peptide and α-skeletal muscle actin, activation of the Akt–p70S6K1 pathway and altered gene expression profile of key components (collagen 1α and fibronectin) and modulators of the ECM (matrix metalloproteinases 2 and 9 and connective tissue growth factor). These changes were correlated with parallel findings of increased TGFβ1 transcription and activation in the LV and elevated active TGFβ1 in plasma of GK rats compared with control animals (Student's t test, P < 0.05 versus age-matched Wistar control animals for all parameters). This is the first report to describe LV structural remodelling in experimental prediabetes. The results suggest that ventricular decompensation pathognomonic of advanced diabetic cardiomyopathy may have possible origins in profibrotic and prohypertrophic mechanisms triggered before the onset of type 2 diabetes mellitus