15 research outputs found
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
Cost-effectiveness and cost-utility analyses of hospital-based home care compared to hospital-based care for children diagnosed with type 1 diabetes; a randomised controlled trial; results after two yearsâ follow-up
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
âDet kĂ€nns som om jag hela tiden ligger nĂ„gra steg bakomâ : En intervjustudie med lĂ€rare i grundsĂ€rskolan om digital kompetens.
LÀxan & FörÀldrar : förÀldrars uppfattningar och attityder till lÀxan undersöks genom sju intervjuer och femtio enkÀter
Denna studie syftar till att genom kvalitativa intervjuer och enkÀtundersökning undersöka hur förÀldrar uppfattar sitt barns hemlÀxa och vilka attityder de har kring lÀxan. Kan förÀldrarnas uppfattningar och attityder skilja sig beroende pÄ vilken utbildningsbakgrund förÀldern innehar?  Studien baseras pÄ kvalitativa intervjuer med sju förÀldrar till elever i grundskolans tidigare Är och en enkÀtundersökning dÀr 50 förÀldrar med samma kriterieurval som ovan deltog. Informanterna som deltar i intervjuerna och enkÀtundersökningen har varierande utbildningsbakgrund. De teoretiska perspektiv som vi anvÀnder till att analyser materialet och som fungerar som ett sökarljus i studien Àr Bourdieus begrepp kapital och habitus. Resultatet som studien visar pÄ Àr att det finns en tendens att förÀldrars attityder till lÀxan skiljer sig och att deras utbildningsnivÄ kan vara en bidragande faktor till detta. Men det huvudsakliga vi kommit fram till i studien Àr att det mer handlar om den enskilda förÀlderns engagemang i deras barns skolgÄng Àn vilken utbildning denne har i bagaget
Water Management and Regulation of Textile Producers in Turkey
Vatten Ă€r en av jordens livsviktiga resurser, en resurs som hela tiden minskar. I delar av vĂ€rlden rĂ„der akut vattenbrist och ofta Ă„terfinns industrier med hög vattenanvĂ€ndning i omrĂ„den med begrĂ€nsad vattentillgĂ„ng. En av dessa industrier Ă€r textilindustrin. Vid textil beredning Ă€r vattenförbrukningen mycket hög och avloppsvattnet Ă€r ofta mycket förorenat. VattenfrĂ„gorna inom textil produktion har fram till idag inte uppmĂ€rksammats i lika stor grad som arbetsrĂ€tts- och kemikaliefrĂ„gorna. Dock Ă€r det den just nu den störst vĂ€xande frĂ„gan och antas bli lika stor som de tvĂ„ nĂ€mnda föregĂ„ngarna.Denna kandidatuppsats Ă€r delvis skriven för Gina Tricots rĂ€kning och för deras del i vatteninitiativet Sweden Textile Water Initiative, (STWI). STWI Ă€r en sammanslutning av ett 30-tal svenska textil- och lĂ€derföretag som tillsammans arbetar för att uppmĂ€rksamma vattenfrĂ„gorna i produktionen och skapa verktyg inför ett förbĂ€ttringsarbete. Gina Tricot ingĂ„r i arbetsgruppen som undersöker lagar i produktionslĂ€nderna. Gina Tricots land Ă€r Turkiet, som blivit vĂ„r bas för denna uppsats.Uppsatsen redogör för vattenĂ„tgĂ„ng i de vanligast förekommande vĂ„tprocesserna i de turkiska fabriker som vi besökt och vilka lagar och regleringar som styr producenterna i landet. Vi har Ă€ven skapat ett förslag för hur Gina Tricot ska implementera STWI:s guideline som fĂ€rdigstĂ€lls 2012.Vid en kontinuerlig process Ă€r vattenĂ„tgĂ„ngen betydligt mindre Ă€n vid en diskontinuerlig process. Den mest vattensnĂ„la processen Ă€r den halv-kontinuerliga. All dosering, av sĂ„vĂ€l kemikalier som fĂ€rg, bör vara automatisk för att minska risken för överdosering och onödiga utslĂ€pp. Ăverloppssköljningar Ă€r mycket vattenslösande och det mest effektiva Ă€r motströmssköljningar. Som produktutvecklare bör skillnader i vattenĂ„tgĂ„ngen för olika fĂ€rgĂ€mnen finnas i Ă„tanke vid val av material och utseende pĂ„ 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 omrĂ„den. Lagarna styr bland annat i vilka mĂ€ngder textilproducenter fĂ„r slĂ€ppa ut olika Ă€mnen i vattendrag. Idag Ă€r det frĂ€mst lagarna The Law on Environment, Urban Wastewater Treatment och Water Pollution Control som styr turkiska textilproducenters vattenhantering.Water is one of earth'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 Tricotâs 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 STWIâs 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 producersâ water management: The Law on Environment, Urban Waste Water Treatment and Water Pollution Control.Program: Textilingenjörsutbildninge
LÀxan & FörÀldrar : förÀldrars uppfattningar och attityder till lÀxan undersöks genom sju intervjuer och femtio enkÀter
Denna studie syftar till att genom kvalitativa intervjuer och enkÀtundersökning undersöka hur förÀldrar uppfattar sitt barns hemlÀxa och vilka attityder de har kring lÀxan. Kan förÀldrarnas uppfattningar och attityder skilja sig beroende pÄ vilken utbildningsbakgrund förÀldern innehar?  Studien baseras pÄ kvalitativa intervjuer med sju förÀldrar till elever i grundskolans tidigare Är och en enkÀtundersökning dÀr 50 förÀldrar med samma kriterieurval som ovan deltog. Informanterna som deltar i intervjuerna och enkÀtundersökningen har varierande utbildningsbakgrund. De teoretiska perspektiv som vi anvÀnder till att analyser materialet och som fungerar som ett sökarljus i studien Àr Bourdieus begrepp kapital och habitus. Resultatet som studien visar pÄ Àr att det finns en tendens att förÀldrars attityder till lÀxan skiljer sig och att deras utbildningsnivÄ kan vara en bidragande faktor till detta. Men det huvudsakliga vi kommit fram till i studien Àr att det mer handlar om den enskilda förÀlderns engagemang i deras barns skolgÄng Àn vilken utbildning denne har i bagaget
Utköp av lÀkemedel mot obstruktiv lungsjukdom : patienter i JÀmtland 30-39 Är, 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 (âŒ6,000 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