Helicobacter pylori genome variability in a framework of familial transmission

<p>Abstract</p> <p>Background</p> <p><it>Helicobacter pylori </it>infection is exceptionally prevalent and is considered to be acquired primarily early in life through person-to-person transmission within the family. <it>H. pylori </it>is a genetically diverse bacterial species, which may facilitate adaptation to new hosts and persistence for decades. The present study aimed to explore the genetic diversity of clonal isolates from a mother and her three children in order to shed light on <it>H. pylori </it>transmission and host adaptation.</p> <p>Results</p> <p>Two different <it>H. pylori </it>strains and strain variants were identified in the family members by PCR-based molecular typing and sequencing of five loci. Genome diversity was further assessed for 15 isolates by comparative microarray hybridizations. The microarray consisted of 1,745 oligonucleotides representing the genes of two previously sequenced <it>H. pylori </it>strains. The microarray analysis detected a limited mean number (± standard error) of divergent genes between clonal isolates from the same and different individuals (1 ± 0.4, 0.1%, and 3 ± 0.3, 0.2%, respectively). There was considerable variability between the two different strains in the family members (147 ± 4, 8%) and for all isolates relative to the two sequenced reference strains (314 ± 16, 18%). The diversity between different strains was associated with gene functional classes related to DNA metabolism and the cell envelope.</p> <p>Conclusion</p> <p>The present data from clonal <it>H. pylori </it>isolates of family members do not support that transmission and host adaptation are associated with substantial sequence diversity in the bacterial genome. However, important phenotypic modifications may be determined by additional genetic mechanisms, such as phase-variation. Our findings can aid further exploration of <it>H. pylori </it>genetic diversity and adaptation.</p

Intestinal Microbiota Regulate Xenobiotic Metabolism in the Liver

BACKGROUND: The liver is the central organ for xenobiotic metabolism (XM) and is regulated by nuclear receptors such as CAR and PXR, which control the metabolism of drugs. Here we report that gut microbiota influences liver gene expression and alters xenobiotic metabolism in animals exposed to barbiturates. PRINCIPAL FINDINGS: By comparing hepatic gene expression on microarrays from germfree (GF) and conventionally-raised mice (SPF), we identified a cluster of 112 differentially expressed target genes predominantly connected to xenobiotic metabolism and pathways inhibiting RXR function. These findings were functionally validated by exposing GF and SPF mice to pentobarbital which confirmed that xenobiotic metabolism in GF mice is significantly more efficient (shorter time of anesthesia) when compared to the SPF group. CONCLUSION: Our data demonstrate that gut microbiota modulates hepatic gene expression and function by altering its xenobiotic response to drugs without direct contact with the liver

Diversity and persistence of Helicobacter pylori

Helicobacter pylori is an exceptionally diverse bacterial species, and every infected individual harbors a unique strain, apart from the strain concordance found in some families. The infection is usually acquired during childhood and once established, persists for life unless treated with antibiotics. When infecting a new host, the bacterium causes inflammation in the gastric lining, which in most cases is asymptomatic, but may progress to chronic gastritis, gastric or duodenal ulcers or gastric cancer. We have performed extensive genetic analyses of H. pylori to give further insight in this immense diversity with a focus on the cytotoxin associated gene pathogenicity island (cag PAI), encoding a type IV secretion system (TFSS). First we studied two subclones, one cag PAI positive and one negative, isolated from the same biopsy. These isolates differed genetically, as determined by microarray genotyping, but were more similar to each other than to any other analyzed strain. In addition, both subclones colonized germ-free transgenic Lewis B expressing mice to an equal density, but the cag PAI negative strain did not colonize conventionally raised mice, while the cag PAI positive did. Investigating reisolates from mice infected for up to 10 months with the cag PAI positive strain revealed genetic stability of the cag PAL In the second paper we determined the nucleotide sequence of the cag PAI in four clinical isolates, two strains isolated from patients with duodenal ulcer, and two from patients with gastric cancer. These strains all harbored a functional TFSS and the overall genetic structure of this 40 kb region was similar, with some interesting exceptions. One completely new hypothetical gene, named HP0521B, was found in three of these strains. This gene was present in about half of the Swedish clinical isolates in our study. In addition, in one duodenal ulcer strain a large insertion or rearrangement in the intergenic region between HP0546 and HP0547 was found. This genomic change did not seem to affect the function of the TFSS. The genetic composition of the H. pylori population in two individuals was examined in paper three. Subclones isolated from two time points with a nine-year interval were used. When sequencing ten loci (-6,000 bp) in three subclones from each time point, only two substitutions were found in one patient and no differences in the other. Further microarray genotyping revealed distinct differences between the subclones within the patients regardless of time of collection, indicating a potent micro-diversity. In the fourth paper we characterized a putative Nudix hydrolase, NudA, in H. pylori. The preferred substrate of NudA was AP4A, a molecule found at elevated concentrations in cells exposed to oxidative and heat stress. When challenging an isogenic mutant of nudA and a wild type with hydrogen peroxide, the mutant was less capable to survive. NudA was found to be an abundant enzyme in H. pylori, expressed at equal amounts at all stages of growth and during stress exposure. This work has increased our understanding of the complex genetic diversity of H. pylori, and revealed the function of a Nudix hydrolase likely to be important for the persistence of this bacterium in the human stomach

Läxan &amp; Föräldrar : föräldrars uppfattningar och attityder till läxan undersöks genom sju intervjuer och femtio enkäter

Denna studie syftar till att genom kvalitativa intervjuer och enkätundersökning undersöka hur föräldrar uppfattar sitt barns hemläxa och vilka attityder de har kring läxan. Kan föräldrarnas uppfattningar och attityder skilja sig beroende på vilken utbildningsbakgrund föräldern innehar?  Studien baseras på kvalitativa intervjuer med sju föräldrar till elever i grundskolans tidigare år och en enkätundersökning där 50 föräldrar med samma kriterieurval som ovan deltog. Informanterna som deltar i intervjuerna och enkätundersökningen har varierande utbildningsbakgrund. De teoretiska perspektiv som vi använder till att analyser materialet och som fungerar som ett sökarljus i studien är Bourdieus begrepp kapital och habitus. Resultatet som studien visar på är att det finns en tendens att föräldrars attityder till läxan skiljer sig och att deras utbildningsnivå kan vara en bidragande faktor till detta. Men det huvudsakliga vi kommit fram till i studien är att det mer handlar om den enskilda förälderns engagemang i deras barns skolgång än vilken utbildning denne har i bagaget

Water Management and Regulation of Textile Producers in Turkey

Vatten är en av jordens livsviktiga resurser, en resurs som hela tiden minskar. I delar av världen råder akut vattenbrist och ofta återfinns industrier med hög vattenanvändning i områden med begränsad vattentillgång. En av dessa industrier är textilindustrin. Vid textil beredning är vattenförbrukningen mycket hög och avloppsvattnet är ofta mycket förorenat. Vattenfrågorna inom textil produktion har fram till idag inte uppmärksammats i lika stor grad som arbetsrätts- och kemikaliefrågorna. Dock är det den just nu den störst växande frågan och antas bli lika stor som de två nämnda föregångarna.Denna kandidatuppsats är delvis skriven för Gina Tricots räkning och för deras del i vatteninitiativet Sweden Textile Water Initiative, (STWI). STWI är en sammanslutning av ett 30-tal svenska textil- och läderföretag som tillsammans arbetar för att uppmärksamma vattenfrågorna i produktionen och skapa verktyg inför ett förbättringsarbete. Gina Tricot ingår i arbetsgruppen som undersöker lagar i produktionsländerna. Gina Tricots land är Turkiet, som blivit vår bas för denna uppsats.Uppsatsen redogör för vattenåtgång i de vanligast förekommande våtprocesserna i de turkiska fabriker som vi besökt och vilka lagar och regleringar som styr producenterna i landet. Vi har även skapat ett förslag för hur Gina Tricot ska implementera STWI:s guideline som färdigställs 2012.Vid en kontinuerlig process är vattenåtgången betydligt mindre än vid en diskontinuerlig process. Den mest vattensnåla processen är den halv-kontinuerliga. All dosering, av såväl kemikalier som färg, bör vara automatisk för att minska risken för överdosering och onödiga utsläpp. Överloppssköljningar är mycket vattenslösande och det mest effektiva är motströmssköljningar. Som produktutvecklare bör skillnader i vattenåtgången för olika färgämnen finnas i åtanke vid val av material och utseende på produkten.1983 infördes den första turkiska miljölagen. Lagen reviderades 2006 för att anpassas till EU:s lagstiftning. Turkiet har ett stort antal vattenlagar som reglerar allt som innefattar vatten, inom alla områden. Lagarna styr bland annat i vilka mängder textilproducenter får släppa ut olika ämnen i vattendrag. Idag är det främst lagarna The Law on Environment, Urban Wastewater Treatment och Water Pollution Control som styr turkiska textilproducenters vattenhantering.Water is one of earth&apos;s vital resources, a resource that is constantly decreasing. In some parts of the world there is acute water scarcity and industries with high water use are often found in areas with limited water availability. One of these industries is the textile industry. The water consumption in textile finishing is very high and the wastewater is often very highly polluted. Water issues in the textile industry have to this date not received as much attention as labor and chemical issues. However, it is the currently the largest growing issue and is expected to be as great as its two predecessors.This report is in part written on behalf of Gina Tricot and for their part in Sweden Textile Water Initiative (STWI). STWI is an association of some 30 Swedish textile and leather companies that are working together to draw attention to water issues in production and create tools for improvement. Gina Tricot is included in the working group that examines laws in producing countries. Gina Tricot’s country is Turkey, which has become the base for this thesis.The thesis describes the water consumption of the most common wet processes in the Turkish factories, that we have visited, and what laws and regulations that govern the producers in the country. We have also created a suggested implementation of STWI’s water management guideline, for Gina Tricot.The water consumption is significantly less in a continuous process than in a discontinuous process. The most water-efficient process is the pad-batch. All dosing of chemicals and dyes should be automatic in order to reduce the risk of overdosing and avoidable emissions. Overflow rinse are highly water-wasting and the most effective rinse is counter flow. Product developers should be aware of the differences in water consumption for various dyes when selecting materials and appearance of the product.In 1983 the first Turkish environmental law was established. It was amended in 2006 to conform to EU legislation. Turkey has a large number of water laws that regulate everything that includes water, in all areas. The laws governing, inter alia, the volumes of various substances textile producers can emit into watercourses. These three laws are primarily governing Turkish textile producers’ water management: The Law on Environment, Urban Waste Water Treatment and Water Pollution Control.Program: Textilingenjörsutbildninge

Läxan &amp; Föräldrar : föräldrars uppfattningar och attityder till läxan undersöks genom sju intervjuer och femtio enkäter

Denna studie syftar till att genom kvalitativa intervjuer och enkätundersökning undersöka hur föräldrar uppfattar sitt barns hemläxa och vilka attityder de har kring läxan. Kan föräldrarnas uppfattningar och attityder skilja sig beroende på vilken utbildningsbakgrund föräldern innehar?  Studien baseras på kvalitativa intervjuer med sju föräldrar till elever i grundskolans tidigare år och en enkätundersökning där 50 föräldrar med samma kriterieurval som ovan deltog. Informanterna som deltar i intervjuerna och enkätundersökningen har varierande utbildningsbakgrund. De teoretiska perspektiv som vi använder till att analyser materialet och som fungerar som ett sökarljus i studien är Bourdieus begrepp kapital och habitus. Resultatet som studien visar på är att det finns en tendens att föräldrars attityder till läxan skiljer sig och att deras utbildningsnivå kan vara en bidragande faktor till detta. Men det huvudsakliga vi kommit fram till i studien är att det mer handlar om den enskilda förälderns engagemang i deras barns skolgång än vilken utbildning denne har i bagaget

Utköp av läkemedel mot obstruktiv lungsjukdom : patienter i Jämtland 30-39 år, 2000-2004

Validerat; 20101217 (root

Slow Genetic Divergence of Helicobacter pylori Strains during Long-Term Colonization

The genetic variability of Helicobacter pylori is known to be high compared to that of many other bacterial species. H. pylori is adapted to the human stomach, where it persists for decades, and adaptation to each host results in every individual harboring a distinctive bacterial population. Although clonal variants may exist within such a population, all isolates are generally genetically related and thus derived from a common ancestor. We sought to determine the rate of genetic change of H. pylori over 9 years in two asymptomatic adult patients. Arbitrary primed PCR confirmed the relatedness of individual subclones within a patient. Furthermore, sequencing of 10 loci (∼6,000 bp) in three subclones per time and patient revealed only two base pair changes among the subclones from patient I. All sequences were identical among the patient II subclones. However, PCR amplification of the highly divergent gene amiA revealed great variation in the size of the gene between the subclones within each patient. Thus, both patients harbored a single strain with clonal variants at both times. We also studied genetic changes in culture- and mouse-passaged strains, and under both conditions no genetic divergence was found. These results suggest that previous estimates of the rate of genetic change in H. pylori within an individual might be overestimates