SalmoNet, an integrated network of ten Salmonella enterica strains reveals common and distinct pathways to host adaptation

Salmonella enterica is a prominent bacterial pathogen with implications on human and animal health. Salmonella serovars could be classified as gastro-intestinal or extra-intestinal. Genome-wide comparisons revealed that extra-intestinal strains are closer relatives of gastro-intestinal strains than to each other indicating a parallel evolution of this trait. Given the complexity of the differences, a systems-level comparison could reveal key mechanisms enabling extra-intestinal serovars to cause systemic infections. Accordingly, in this work, we introduce a unique resource, SalmoNet, which combines manual curation, high-throughput data and computational predictions to provide an integrated network for Salmonella at the metabolic, transcriptional regulatory and protein-protein interaction levels. SalmoNet provides the networks separately for five gastro-intestinal and five extra-intestinal strains. As a multi-layered, multi-strain database containing experimental data, SalmoNet is the first dedicated network resource for Salmonella. It comprehensively contains interactions between proteins encoded in Salmonella pathogenicity islands, as well as regulatory mechanisms of metabolic processes with the option to zoom-in and analyze the interactions at specific loci in more detail. Application of SalmoNet is not limited to strain comparisons as it also provides a Salmonella resource for biochemical network modeling, host-pathogen interaction studies, drug discovery, experimental validation of novel interactions, uncovering new pathological mechanisms from emergent properties and epidemiological studies. SalmoNet is available at http://salmonet.org

Кинетика восстановления железа при восстановительной плавке рудоугольных окатышей

Исследовано влияние интенсивности теплообмена на кинетику восстановления железа в процессе плавки рудоугольных окатышей. Показано, что с ростом интенсивности теплообмена повышается скорость восстановительных процессов. Вследствие роста коэффициента теплообмена увеличивается глубина восстановленного слоя окатыша, существенно изменяются его структура и химический состав образующейся металлической фазы.Досліджено вплив інтенсивності теплообміну на кінетику відновлення заліза в процесі плавки рудовугільних окатишів. Показано, що при зростанні інтенсивності теплообміну підвищується швидкість відновлювальних процесів. Внаслідок зростання коефіцієнту теплообміну збільшується глибина відновленого шару окатиша, суттєво змінюються його структура та хімічний склад металевої фази, що утворюється.Influence of intensity of heat exchange is investigational on kinetics reduction of iron in the process of melting ore-coal pellets. It is rotined that speed of reduction processes rises with growth of intensity of heat exchange. Because of growth of coefficient of heat exchange the depth of the recovered layer of pellet is increased, his structure and chemical composition of appearing metallic phase changes substantially

Mitochondrial Dynamics and Activity in Legionella-Infected Cells

International audienceThe study of Legionella pneumophila interactions with host mitochondria during infection has been historically limited by the techniques available to analyze and quantify mitochondrial dynamics and activity in living cells. Recently, new, powerful techniques such as high-content microscopy or mitochondrial respiration assays (Seahorse) have been developed to quantitatively analyze mitochondrial parameters. Here we present state-of-the-art methods adapted to analyze mitochondrial dynamics and activity during Legionella infection of living human primary macrophages

Caspase-8 promotes c-Rel–dependent inflammatory cytokine expression and resistance against Toxoplasma gondii

Caspase-8 is a key integrator of cell survival and cell death decisions during infection and inflammation. Following engagement of tumor necrosis factor superfamily receptors or certain Toll-like receptors (TLRs), caspase-8 initiates cell-extrinsic apoptosis while inhibiting RIPK3-dependent programmed necrosis. In addition, caspase-8 has an important, albeit less well understood, role in cell-intrinsic inflammatory gene expression. Macrophages lacking caspase-8 or the adaptor FADD have defective inflammatory cytokine expression and inflammasome priming in response to bacterial infection or TLR stimulation. How caspase-8 regulates cytokine gene expression, and whether caspase-8–mediated gene regulation has a physiological role during infection, remain poorly defined. Here we demonstrate that both caspase-8 enzymatic activity and scaffolding functions contribute to inflammatory cytokine gene expression. Caspase-8 enzymatic activity was necessary for maximal expression of Il1b and Il12b, but caspase-8 deficient cells exhibited a further decrease in expression of these genes. Furthermore, the ability of TLR stimuli to induce optimal IκB kinase phosphorylation and nuclear translocation of the nuclear factor kappa light chain enhancer of activated B cells family member c-Rel required caspase activity. Interestingly, overexpression of c-Rel was sufficient to restore expression of IL-12 and IL-1β in caspase-8–deficient cells. Moreover, Ripk3−/−Casp8−/− mice were unable to control infection by the intracellular parasite Toxoplasma gondii, which corresponded to defects in monocyte recruitment to the peritoneal cavity, and exogenous IL-12 restored monocyte recruitment and protection of caspase-8–deficient mice during acute toxoplasmosis. These findings provide insight into how caspase-8 controls inflammatory gene expression and identify a critical role for caspase-8 in host defense against eukaryotic pathogens

Caspase-8 promotes c-Rel–dependent inflammatory cytokine expression and resistance against Toxoplasma gondii

Caspase-8 is a key integrator of cell survival and cell death decisions during infection and inflammation. Following engagement of tumor necrosis factor superfamily receptors or certain Toll-like receptors (TLRs), caspase-8 initiates cell-extrinsic apoptosis while inhibiting RIPK3-dependent programmed necrosis. In addition, caspase-8 has an important, albeit less well understood, role in cell-intrinsic inflammatory gene expression. Macrophages lacking caspase-8 or the adaptor FADD have defective inflammatory cytokine expression and inflammasome priming in response to bacterial infection or TLR stimulation. How caspase-8 regulates cytokine gene expression, and whether caspase-8–mediated gene regulation has a physiological role during infection, remain poorly defined. Here we demonstrate that both caspase-8 enzymatic activity and scaffolding functions contribute to inflammatory cytokine gene expression. Caspase-8 enzymatic activity was necessary for maximal expression of Il1b and Il12b, but caspase-8 deficient cells exhibited a further decrease in expression of these genes. Furthermore, the ability of TLR stimuli to induce optimal IκB kinase phosphorylation and nuclear translocation of the nuclear factor kappa light chain enhancer of activated B cells family member c-Rel required caspase activity. Interestingly, overexpression of c-Rel was sufficient to restore expression of IL-12 and IL-1β in caspase-8–deficient cells. Moreover, Ripk3−/−Casp8−/− mice were unable to control infection by the intracellular parasite Toxoplasma gondii, which corresponded to defects in monocyte recruitment to the peritoneal cavity, and exogenous IL-12 restored monocyte recruitment and protection of caspase-8–deficient mice during acute toxoplasmosis. These findings provide insight into how caspase-8 controls inflammatory gene expression and identify a critical role for caspase-8 in host defense against eukaryotic pathogens

The removal of a culture-historical dam for improved resilience of urban nature

Tikkurila dam is in the River Keravanjoki in the centre of Vantaa and it has lost its original function of providing water power for linseed oil production. The dam is an important part of the historical factory surroundings of Vernissa, but it is in poor condition and in need of refurbishing. The dam is an obstruction for migratory fish species that try to climb upstream to spawn and the waterfront is heavily focused by recreational pressure. All these factors combined have set the dam removal decision-making process in motion. The project has been carried out by Ramboll Finland Oy for the city of Vantaa since 2014 and the plan implementation and dam removal is expected to take place in 2019. This thesis introduces the project process and the case area of Tikkurila dam. It also aspires to evaluate the physical, biological and cultural changes in the case area resulting from the dam removal and river restoration and to form a monitoring programme to survey the main outcomes. One objective is to review how the benefits and losses in ecological quality compare with those in cultural quality. A literature review has been conducted on free-flowing rivers, the effects of dams on river integrity and ecosystem, dam removal and river restoration processes and possible dam removal outcomes. The evaluation of changes has been performed by using the ecosystem services approach as a framework. The study indicates that the ecological benefits obtained by performing the dam removal and river restoration are greater than the losses in some cultural services (i.e. culture-historical surroundings). The dam removal will affect many services in the area, but most importantly will restore the integrity of the natural river ecosystem. The effects should be monitored through key indicators of the most essential services. The study was cohesive with the literature review and it suggests that dam removal projects should be carried out as a multi-disciplinary and co-operative process.Tikkurilan pato sijaitsee Keravanjoessa, Vantaan Tikkurilassa. Se on menettänyt alkuperäisen tarkoituksensa tuottaa vesivoimaa vernissaöljyn tuotantoon, mutta on edelleen tärkeä osa Vernissan teollisuushistoriaa. Pato vuotaa ja on laajan kunnostuksen tarpeessa. Pato ja huonosti toimiva kalaporras muodostavat kulkuesteen vaeltaville meritaimenille, jotka yrittävät päästä ylävirtaan kutemaan ja jokirantaan kohdistuu suuria virkistyksellisiä paineita. Nämä tekijät yhdessä vaikuttivat päätökseen aloittaa selvitys padon poiston mahdollisuuksista. Projektin on tehnyt Ramboll Finland Oy Vantaan kaupungille. Esiselvitys käynnistettiin vuonna 2014 ja suunnitelman toteutus ja padon poisto tulee todennäköisesti tapahtumaan kesällä 2019. Tämä opinnäytetyö kuvailee projektin eri vaiheet ja Tikkurilan padon alueen ominaisuudet. Opinnäytetyössä pyritään arvioimaan padon poiston ja jokikunnostuksen aiheuttamat fyysiset ja kulttuuriset muutokset alueella ja muodostamaan seurantaohjelma, joka keskittyy tärkeimmiksi havaittuihin muutoksiin. Yksi tavoite on myös arvioida muutoksesta aiheutuvien ekologisten ja kulttuuristen ominaisuuksien hyötyjä ja haittoja keskenään. Kirjallisuustutkimus on tehty vapaista virtavesistä, patojen vaikutuksista jokien eheyteen ja ekosysteemiin, patojen poiston ja jokikunnostuksen prosesseista ja mahdollisista patojen poiston lopputuloksista. Muutosten arviointiin on käytetty ekosysteemipalvelu-näkökulmaa, koska se mahdollistaa kulttuuristen ja ekologisten vaikutusten vertailun rinnakkain. Tutkimuksen mukaan padon poiston ja jokikunnostuksen ekologiset hyödyt ovat suuremmat, kuin padon poiston kulttuuriset haitat. Padon poistolla on vaikutuksia moniin ekosysteemipalveluihin alueella, mutta tärkeimpänä on joen eheyden ja luonnollisen ekosysteemin palautuminen. Vaikutuksien seurantaa tulisi tehdä pääasiassa avainindikaattorien kautta, jotka muodostuvat projektin tavoitteista. Tutkimuksen tulokset ovat yhteneväiset kirjallisuustutkimuksen kanssa ja sen mukaan padon poisto-projektit tulisi toteuttaa monialaisina ja yhteistyöpainotteisina prosesseina

Hydrogen peroxide release by bacteria suppresses inflammasome-dependent innate immunity

Hydrogen peroxide (H2O2) has a major function in host-microbial interactions. Although most studies have focused on the endogenous H2O2 produced by immune cells to kill microbes, bacteria can also produce H2O2. How microbial H2O2 influences the dynamics of host-microbial interactions is unclear. Here we show that H2O2 released by Streptococcus pneumoniae inhibits inflammasomes, key components of the innate immune system, contributing to the pathogen colonization of the host. We also show that the oral commensal H2O2-producing bacteria Streptococcus oralis can block inflammasome activation. This study uncovers an unexpected role of H2O2 in immune suppression and demonstrates how, through this mechanism, bacteria might restrain the immune system to co-exist with the host