The clc element and related genomic islands in Proteobacteria

Genomic islands are large DNA segments, present in most bacterial genome, that are acquired via horizontal gene transfer and contribute to the rapid bacterial evolution and adaptation of the host cell. Here we focus on the clc element (or ICEclc), a 103‑kb genomic island first discovered in Pseudomonas knackmussii B13, as a model of this diverse group of mobile genetic elements. ICEclc is normally integrated in the host bacterial chromosome but can excise and transfer to a new host by conjugation. In this chapter we review the basic features of ICEclc, the mechanisms of its life‑style as well as evolutionary relationships with other known and unknown elements in a variety of Proteobacteria.

European genetic diversity and susceptibility to pathogens.

Infectious diseases, both in their endemic and epidemic forms, have shaped the human genome. Ecology has also contributed to geographically constrained pressures on human populations. There are now multiple examples of population-specific genetic variants that modulate susceptibility to infection - several of which have been observed solely in Europeans. The pathogen genome also mutates and adapts to individuals and common alleles in populations. The current understanding has benefited from genome-wide association studies as well as from rapid progress in the genetic characterization of Mendelian immunodeficiencies that are defined by susceptibility to specific pathogens. It is expected that current efforts to characterize rare human genetic variants will contribute to the understanding of severe manifestations of common infections in European and other human groups.

Functional plasticity of the LACK-reactive Vbeta4-Valpha8 CD4(+) T cells normally producing the early IL-4 instructing Th2 cell development and susceptibility to Leishmania major in BALB / c mice.

Early production of IL-4 by LACK-reactive Vbeta4-Valpha8 CD4(+) T cells instructs aberrant Th2 cell development and susceptibility to Leishmania major in BALB / c mice. This was demonstrated using Vbeta4(+)-deficient BALB / c mice as a result of chronic infection with MMTV (SIM), a mouse mammary tumor virus expressing a Vbeta4-specific superantigen. The early IL-4 response was absent in these mice which develop a Th1 response to L. major. Here, we studied the functional plasticity of LACK-reactive Vbeta4-Valpha8 CD4(+) T cells using BALB/ c mice inoculated with L. major shortly after infection with MMTV (SIM), i. e. before deletion of Vbeta4(+) cells. These mice fail to produce the early IL-4 response to L. major and instead exhibit an IFN-gamma response that occurs within LACK-reactive Vbeta4-Valpha8 CD4(+) T cells. Neutralization of IFN-gamma restores the production of IL-4 by these cells. These data suggest that the functional properties of LACK-reactive Vbeta4-Valpha8 CD4(+) T cells are not irreversibly fixed.

The Arabidopsis PHYTOCHROME KINASE SUBSTRATE2 protein is a phototropin signaling element that regulates leaf flattening and leaf positioning.

In Arabidopsis (Arabidopsis thaliana), the blue light photoreceptor phototropins (phot1 and phot2) fine-tune the photosynthetic status of the plant by controlling several important adaptive processes in response to environmental light variations. These processes include stem and petiole phototropism (leaf positioning), leaf flattening, stomatal opening, and chloroplast movements. The PHYTOCHROME KINASE SUBSTRATE (PKS) protein family comprises four members in Arabidopsis (PKS1-PKS4). PKS1 is a novel phot1 signaling element during phototropism, as it interacts with phot1 and the important signaling element NONPHOTOTROPIC HYPOCOTYL3 (NPH3) and is required for normal phot1-mediated phototropism. In this study, we have analyzed more globally the role of three PKS members (PKS1, PKS2, and PKS4). Systematic analysis of mutants reveals that PKS2 (and to a lesser extent PKS1) act in the same subset of phototropin-controlled responses as NPH3, namely leaf flattening and positioning. PKS1, PKS2, and NPH3 coimmunoprecipitate with both phot1-green fluorescent protein and phot2-green fluorescent protein in leaf extracts. Genetic experiments position PKS2 within phot1 and phot2 pathways controlling leaf positioning and leaf flattening, respectively. NPH3 can act in both phot1 and phot2 pathways, and synergistic interactions observed between pks2 and nph3 mutants suggest complementary roles of PKS2 and NPH3 during phototropin signaling. Finally, several observations further suggest that PKS2 may regulate leaf flattening and positioning by controlling auxin homeostasis. Together with previous findings, our results indicate that the PKS proteins represent an important family of phototropin signaling proteins.

Schizophrenia and oxidative stress: glutamate cysteine ligase modifier as a susceptibility gene.

Oxidative stress could be involved in the pathophysiology of schizophrenia, a major psychiatric disorder. Glutathione (GSH), a redox regulator, is decreased in patients' cerebrospinal fluid and prefrontal cortex. The gene of the key GSH-synthesizing enzyme, glutamate cysteine ligase modifier (GCLM) subunit, is strongly associated with schizophrenia in two case-control studies and in one family study. GCLM gene expression is decreased in patients' fibroblasts. Thus, GSH metabolism dysfunction is proposed as one of the vulnerability factors for schizophrenia.

Adoption av träkomposit teknologi på svenska trähusmarknaden

Syftet med uppsatsen är att kategorisera träkomposit teknologi adoption på svenska trähusmarknaden genom fallstudie av trähustillverkare och fasadbehandlare. Som undersöknings metod har intervjueroch facklitteratur använts. Med hjälp av litteraturmaterialet sammanställdes enteoretisk referensram, vad efter sedan fallföretagen intervjuades. Genom insamlade sekundärdata betraktades företaget i den teoretiska referensramen. Undersökningens teorin baserar sig på adoption av innovation. Inledningsvis redogörs traditionell segmentering av industriella marknader och sedan segmentering efter kundlivscykel. Tyngdpunkten är ändå på teknologi adoption livscykel. Empirin är fallstudie av modul, storblock trähustillverkare och fasadbehandlare. Företagets situation studeras inom teoretiska referensramen för att kunna göra en analys avadoptionen och göra slutsatser om produktlanseringen. Rekommendation är några aspekter som innobuild bör beakta vid försäljning av Fasec-fasadsystem. Undersökningen torde kunna användas som stöd vid adoption av en innovation.

La seguretat. Element clau del model turístic de Catalunya

El turisme és un sector de sectors amb els que el turista interacciona directament com a un ciutadà més i és aquesta complexa cadena de valor el que acaba conformant la experiència turística. La visió 2020 i els objectius estratègics 2016 conformen la base sobre la que s’han proposat les directrius nacionals 2020 i el pla d’accions 2013-2016.

Alternatives per a l’engreix ecològic de bovins: la sal com a element regulador del consum de pinso en vedells de la raça Parda de Montaña

El present treball proposa l’addició d’un 10% de sal al pinso d’engreix d’11 vedells de la raça Parda de Montaña, com a sistema per limitar-ne el consum sense haver de fer ús de mà d’obra complementària ni de sistemes mecanitzats que en controlin la quantitat de consum. Aquest % de sal, pretén aconseguir una reducció en la palatabilitat del pinso de consum dels animals, aconseguint així uns menors valors d’ingestió de concentrat per un major consum de farratge. Aquesta relació quantitativa té com a objectiu, aconseguir la introducció d’aquests animals en el marc de la producció ecològica, que estableix una ràtio de consum de farratge vs concentrat de 60 : 40. El grup d’11 vedells, prèviament esmentat, és comparat amb una altre grup, també d’11 vedells i de la mateixa raça i edat, que són alimentats amb el mateix fenc d’alfals, però amb pinso convencional i no amb el complementat amb sal

IL1B and DEFB1 Polymorphisms Increase Susceptibility to Invasive Mold Infection After Solid-Organ Transplantation.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) in immune genes have been associated with susceptibility to invasive mold infection (IMI) among hematopoietic stem cell but not solid-organ transplant (SOT) recipients. METHODS: Twenty-four SNPs from systematically selected genes were genotyped among 1101 SOT recipients (715 kidney transplant recipients, 190 liver transplant recipients, 102 lung transplant recipients, 79 heart transplant recipients, and 15 recipients of other transplants) from the Swiss Transplant Cohort Study. Association between SNPs and the end point were assessed by log-rank test and Cox regression models. Cytokine production upon Aspergillus stimulation was measured by enzyme-linked immunosorbent assay in peripheral blood mononuclear cells (PBMCs) from healthy volunteers and correlated with relevant genotypes. RESULTS: Mold colonization (n = 45) and proven/probable IMI (n = 26) were associated with polymorphisms in the genes encoding interleukin 1β (IL1B; rs16944; recessive mode, P = .001 for colonization and P = .00005 for IMI, by the log-rank test), interleukin 1 receptor antagonist (IL1RN; rs419598; P = .01 and P = .02, respectively), and β-defensin 1 (DEFB1; rs1800972; P = .001 and P = .0002, respectively). The associations with IL1B and DEFB1 remained significant in a multivariate regression model (P = .002 for IL1B rs16944; P = .01 for DEFB1 rs1800972). The presence of 2 copies of the rare allele of rs16944 or rs419598 was associated with reduced Aspergillus-induced interleukin 1β and tumor necrosis factor α secretion by PBMCs. CONCLUSIONS: Functional polymorphisms in IL1B and DEFB1 influence susceptibility to mold infection in SOT recipients. This observation may contribute to individual risk stratification.

Genes outside The Hla Region affecting Susceptibility to Type 1 Diabetes - The Role of Iddm2 and Iddm9 in the Finnish Population

Tyypin 1 diabeteksen perinnöllinen alttius Suomessa - HLA-alueen ulkopuolisten alttiuslokusten IDDM2 ja IDDM9 rooli taudin periytymisessä HLA-alue, joka sijaitsee kromosomissa 6p21.3, vastaa noin puolesta perinnöllisestä alttiudesta sairastua tyypin 1 diabetekseen. Myös HLA-alueen ulkopuolisten lokusten on todettu liittyvän sairausalttiuteen. Näistä kolmen lokuksen on varmistettu olevan todellisia alttiuslokuksia ja lisäksi useiden muiden, vielä varmistamattomien lokusten, on todettu liittyvän sairausalttiuteen. Tässä tutkimuksessa 12:n HLA-alueen ulkopuolisen alttiuslokuksen kytkentä tyypin 1 diabetekseen tutkittiin käyttäen 107:aa suomalaista multiplex-perhettä. Jatkotutkimuksessa analysoitiin IDDM9-alueen kytkentä ja assosiaatio sairauteen laajennetuissa perhemateriaaleissa sekä IDDM2-alueen mahdollinen interaktio HLA-alueen kanssa sairauden muodostumisessa. Lisäksi suoritettiin IDDM2-alueen suojaavien haplotyyppien alatyypitys tarkoituksena tutkia eri haplotyyppien käyttökelpoisuutta sairastumisriskin tarkempaa ennustamista varten. Ensimmäisessä kytkentätutkimuksessa ei löytynyt koko genomin tasolla merkitsevää tai viitteellistä kytkentää tutkituista HLA-alueen ulkopuolisista lokuksista. Voimakkain havaittu nimellisen merkitsevyyden tavoittava kytkentä nähtiin IDDM9-alueen markkerilla D3S3576 (MLS=1.05). Tutkimuksessa ei kyetty varmistamaan tai sulkemaan pois aiempia kytkentähavaintoja tutkituilla lokuksilla, mutta IDDM9-alueen jatkotutkimuksessa havaittu voimakas kytkentä (MLS=3.4) ja merkitsevä assosiaatio (TDT p=0.0002) viittaa vahvasti siihen, että 3q21-alueella sijaitsee todellinen tyypin 1 diabeteksen alttiusgeeni, jolloin alueen kattava assosiaatiotutkimus olisi perusteltu jatkotoimenpide. Sairauteen altistava IDDM2-alueen MspI-2221 genotyyppi CC oli nimellisesti yleisempi matalan tai kohtalaisen HLA-sairastumisriskin diabeetikoilla, verrattuna korkean HLA-riskin potilaisiin (p=0.05). Myös genotyyppijakauman vertailu osoitti merkitsevää eroa ryhmien välillä (p=0.01). VNTR-haplotyyppitutkimus osoitti, että IIIA/IIIA-homotsygootin sairaudelta suojaava vaikutus on merkitsevästi voimakkaampi kuin muiden luokka III:n genotyypeillä. Nämä tulokset viittaavat IDDM2-HLA -vuorovaikutukseen sekä siihen että IDDM2-alueen haplotyyppien välillä esiintyy etiologista heterogeniaa. Tämän johdosta IDDM2-alueen haplotyyppien tarkempi määrittäminen voisi tehostaa tyypin 1 diabeteksen riskiarviointia.

Trace element monitoring in the ICU: quality and economic impact of a change in sampling practice.

BACKGROUND & AIMS: Trace elements (TE) are involved in the immune and antioxidant defences which are of particular importance during critical illness. Determining plasma TE levels is costly. The present quality control study aimed at assessing the economic impact of a computer reminded blood sampling versus a risk guided on-demand monitoring of plasma concentrations of selenium, copper, and zinc. METHODS: Retrospective analysis of 2 cohorts of patients admitted during 6 months periods in 2006 and 2009 to the ICU of a University hospital. INCLUSION CRITERIA: to receive intravenous micronutrient supplements and/or to have a TE sampling during ICU stay. The TE samplings were triggered by computerized reminder in 2006 versus guided by nutritionists in 2009. RESULTS: During the 2 periods 636 patients met the inclusion criteria out of 2406 consecutive admissions, representing 29.7% and 24.9% respectively of the periods' admissions. The 2009 patients had higher SAPS2 scores (p = 0.02) and lower BMI compared to 2006 (p = 0.007). The number of laboratory determinations was drastically reduced in 2009, particularly during the first week, despite the higher severity of the cohort, resulting in à 55% cost reduction. CONCLUSIONS: The monitoring of TE concentrations guided by a nutritionist resulted in a reduction of the sampling frequency, and targeting on the sickest high risk patients, requiring a nutritional prescription adaptation. This control leads to cost reduction compared to an automated sampling prescription.

A survey of transposable element classification systems--a call for a fundamental update to meet the challenge of their diversity and complexity.

The increase of publicly available sequencing data has allowed for rapid progress in our understanding of genome composition. As new information becomes available we should constantly be updating and reanalyzing existing and newly acquired data. In this report we focus on transposable elements (TEs) which make up a significant portion of nearly all sequenced genomes. Our ability to accurately identify and classify these sequences is critical to understanding their impact on host genomes. At the same time, as we demonstrate in this report, problems with existing classification schemes have led to significant misunderstandings of the evolution of both TE sequences and their host genomes. In a pioneering publication Finnegan (1989) proposed classifying all TE sequences into two classes based on transposition mechanisms and structural features: the retrotransposons (class I) and the DNA transposons (class II). We have retraced how ideas regarding TE classification and annotation in both prokaryotic and eukaryotic scientific communities have changed over time. This has led us to observe that: (1) a number of TEs have convergent structural features and/or transposition mechanisms that have led to misleading conclusions regarding their classification, (2) the evolution of TEs is similar to that of viruses by having several unrelated origins, (3) there might be at least 8 classes and 12 orders of TEs including 10 novel orders. In an effort to address these classification issues we propose: (1) the outline of a universal TE classification, (2) a set of methods and classification rules that could be used by all scientific communities involved in the study of TEs, and (3) a 5-year schedule for the establishment of an International Committee for Taxonomy of Transposable Elements (ICTTE).

Antibiotic susceptibility and molecular epidemiology of Panton-Valentine leukocidin-positive meticillin-resistant Staphylococcus aureus: An international survey

The antibiotic susceptibility and molecular epidemiology of Panton-Valentine leukocidin (PVL)-positive meticillin-resistant Staphylococcus aureus (MRSA) isolates reported from 17 countries in the Americas, Europe and, Australia-Asia were analysed. Among a total of 3236 non-duplicate isolates, the lowest susceptibility was observed to erythromycin in all regions. Susceptibility to ciprofloxacin showed large variation (25%, 75% and 84% in the Americas, Europe and Australia-Asia, respectively). Two vancomycin-intermediate PVL-positive MRSA isolates were reported, one from Hong Kong and the other from The Netherlands. Resistance to trimethoprim/sulfamethoxazole and linezolid was <1%. Among 1798 MRSA isolates from 13 countries that were tested for the requested 10 non-β-lactam antibiotics, 49.4% were multisusceptible. However, multiresistant isolates (resistant to at least three classes of non-β-lactam antibiotics) were reported from all regions. Sequence type 30 (ST30) was reported worldwide, whereas ST80 and ST93 were exclusive to Europe and Australia, respectively. USA300 and related clones (ST8) are progressively replacing the ST80 clone in several European countries. Eight major clusters were discriminated by multilocus variable-number tandem repeat assay (MLVA), showing a certain geographic specificity. PVL-positive MRSA isolates frequently remain multisusceptible to non-β-lactam agents, but multiresistance is already prevalent in all regions. Surveillance of MRSA susceptibility patterns should be monitored to provide clinicians with the most current information regarding changes in resistance patterns.

In vivo effect of flucloxacillin in experimental endocarditis caused by mecC-positive staphylococcus aureus showing temperature-dependent susceptibility in vitro.

Methicillin-resistant Staphylococcus aureus (MRSA) carrying the mecC gene (mecC-MRSA) exhibited at 37°C MICs of oxacillin close to those of methicillin-susceptible S. aureus (MSSA). We investigated whether at this temperature, mecC-MRSA strains respond to flucloxacillin treatment like MSSA strains, using a rat model of endocarditis. Flucloxacillin (human-like kinetics of 2 g intravenously every 6 h) cured 80 to 100% of aortic vegetations infected with five different mecC-MRSA strains. These results suggest that mecC-MRSA infections may successfully respond to treatment with β-lactams.