Dynamics of the Type I Interferon Response During Immunosuppressive Therapy in Rheumatoid Arthritis

Objective: The type I interferon (IFN) response in rheumatoid arthritis (RA) has been extensively studied in relation to therapy with biological DMARDs (bDMARDs). However, the effect of conventional synthetic (cs)DMARDs and glucocorticoids (GCs) on IFN response gene (IRG) expression remains largely unknown, even though csDMARDS are used throughout all disease phases, including simultaneously with biologic therapy. This study was aimed to determine the dynamics of IFN response upon immunosuppressive treatment.Methods: Whole blood was collected in PAXgene tubes from 35 RA patients who received either COBRA therapy (combination of prednisone, initially 60 mg, methotrexate and sulfasalazine) (n = 14) or COBRA-light therapy (prednisone, initially 30 mg, and methotrexate) (n = 21). Expression of 10 IRGs was determined by real-time PCR at baseline (T0), after 4 weeks (T4), and 13 weeks (T13) of treatment. IRG selection was based on the differential presence of transcription factor binding sites (TFBS), in order to study the therapy effect on different pathway components involved in IFN signaling.Results: Seven of the 10 IRGs displayed significant changes during treatment (p ≤ 0.016). These 7 IRGs all displayed a particularly pronounced decrease between T0 and T4 (≥1.6-fold, p ≤ 0.0059). The differences between IRG sensitivity to the treatment appeared related to the presence of TFBS for STAT1 and IRF proteins within the genes. The extent of the decreases between T0 and T4 was similar for the COBRA- and COBRA-light-treated group, despite the differences in drug combination and doses in those groups. Between T4 and T13, however, IRG expression in the COBRA-light-treated group displayed a significant increase, whereas it remained stable or decreased even further in most COBRA-treated patients (comparison of mean fold changes, p = 0.011). A significant association between IRG dynamics and clinical response to therapy was not detected.Conclusions: Immunosuppressive treatment with csDMARDs, in this case a combination of prednisolone, methotrexate and sulfasalazine, substantially downregulates the IFN response in RA patients. The dynamics of this downregulation were partly dependent on the presence of TFBS within the IRGs and the combination and dosages of agents, but they were irrespective of the clinical response to therapy

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació

A computational and spectroscopic study of the gas-phase conformers of adrenaline

The conformational landscapes of the neurotransmitter 1-adrenaline (1-epinephrine) and its diastereoisomer pseudo-adrenaline, isolated in the gas phase and un-protonated, have been investigated by using a combination of mass-selected ultraviolet and infrared holeburn spectroscopy, following laser desorption of the sample into a pulsed supersonic argon jet, and DFT and ab initio computation (at the B3LYP/6-31+G*, MP2/6-31+G* and MP2/aug-cc-pVDZ levels of theory). Both for adrenaline and its diastereoisomer, pseudo-adrenaline, one dominant molecular conformation, very similar to the one seen in noradrenaline, has been observed. It could be assigned to an extended side-chain structure (AG1a) stabilized by an OH -&gt; N intramolecular hydrogen bond. An intramolecular hydrogen bond is also formed between the neighbouring hydroxyl groups on the catechol ring. The presence of further conformers for both diastereoisomers could not be excluded, but overlapping electronic spectra and low ion signals prevented further assignments.</p

Neurotransmitters in the gas phase: hydrated noradrenaline

The conformational and molecular structures of singly hydrated noradrenaline complexes have been explored through a combination of electronic structure computation (at the B3LYP/ 6- 31+ G*, MP2/ 6- 31+ G* and MP2/ aug-cc-pVDZ levels of theory) and mass-selected ultraviolet and infrared ion-dip spectroscopy following laser ablation of the neurotransmitter into a freely expanding moist argon jet. Under these conditions, almost all the hydrated complexes are located in the global minimum energy configuration, associated with an extended, AG1a, ethanolamine side-chain conformation; the water molecule, which is located slightly above the plane of the catechol ring, is bound primarily as a proton acceptor to the m-OH substituent, and only weakly, as a proton donor, to the hydroxyl group on the side chain.</p

Data from: Relationships between fungal community composition in decomposing leaf litter and home-field advantage effects

Increasing evidence suggests that specific interactions between microbial decomposers and plant litter, named home field advantage (HFA), influence litter breakdown. However, we still have limited understanding of whether HFA relates to specific microbiota, and whether specialized microbes originate from the soil or from the leaf microbiome. Here, we disentangle the roles of soil origin, litter types, and the microbial community already present on the leaf litter in determining fungal community composition on decomposing leaf litter and HFA. We collected litters and associated soil samples from a secondary succession gradient ranging from herbaceous vegetation on recently abandoned ex‐arable fields to forest representing the end stage of succession. In a greenhouse, sterilized and unsterilized leaf litters were decomposed for 12 months in soils from early to late successional stages according to a full factorial design. At the end, we examined fungal community composition on the decomposing litter. Fungal communities on decomposed late‐successional litter in late‐successional soil differed from those in early‐ and mid‐successional stage litter and soil combinations. Soil source had the strongest impact on litter fungal composition when using sterilized litter, while the impact of litter type was strongest when using unsterilized litter. Overall, we observed HFA, as litter decomposition was accelerated in home soils. Increasing HFA did not relate to the dissimilarity in overall fungal composition, but there was increasing dissimilarity in the relative abundance of the most dominant fungal taxon between decomposing litter in home and away soils. We conclude that early, mid and late succession litter types did not exert strong selection effects on colonization by microorganisms from the soil species pool. Instead, fungal community composition on decomposing litter differed substantially between litter types for unsterilized litter, suggesting that the leaf microbiome, either directly or indirectly, is an important determinant of fungal community composition on decomposing leaves. HFA related most strongly to the abundance of the most dominant fungal taxa on the decomposing litter, suggesting that HFA may be attributed to some specific dominant fungi rather than to responses of the whole fungal community

Mass loss and environmental data

This file contains data on litter mass loss and environmental conditions (litter quality + soil properties

Data from: Relationships between fungal community composition in decomposing leaf litter and home-field advantage effects

Increasing evidence suggests that specific interactions between microbial decomposers and plant litter, named home field advantage (HFA), influence litter breakdown. However, we still have limited understanding of whether HFA relates to specific microbiota, and whether specialized microbes originate from the soil or from the leaf microbiome. Here, we disentangle the roles of soil origin, litter types, and the microbial community already present on the leaf litter in determining fungal community composition on decomposing leaf litter and HFA. We collected litters and associated soil samples from a secondary succession gradient ranging from herbaceous vegetation on recently abandoned ex‐arable fields to forest representing the end stage of succession. In a greenhouse, sterilized and unsterilized leaf litters were decomposed for 12 months in soils from early to late successional stages according to a full factorial design. At the end, we examined fungal community composition on the decomposing litter. Fungal communities on decomposed late‐successional litter in late‐successional soil differed from those in early‐ and mid‐successional stage litter and soil combinations. Soil source had the strongest impact on litter fungal composition when using sterilized litter, while the impact of litter type was strongest when using unsterilized litter. Overall, we observed HFA, as litter decomposition was accelerated in home soils. Increasing HFA did not relate to the dissimilarity in overall fungal composition, but there was increasing dissimilarity in the relative abundance of the most dominant fungal taxon between decomposing litter in home and away soils. We conclude that early, mid and late succession litter types did not exert strong selection effects on colonization by microorganisms from the soil species pool. Instead, fungal community composition on decomposing litter differed substantially between litter types for unsterilized litter, suggesting that the leaf microbiome, either directly or indirectly, is an important determinant of fungal community composition on decomposing leaves. HFA related most strongly to the abundance of the most dominant fungal taxa on the decomposing litter, suggesting that HFA may be attributed to some specific dominant fungi rather than to responses of the whole fungal community

Relationships between fungal community composition in decomposing leaf litter and home‐field advantage effects

1. Increasing evidence suggests that specific interactions between microbial decomposers and plant litter, named home‐field advantage (HFA), influence litter breakdown. However, we still have limited understanding of whether HFA relates to specific microbiota, and whether specialized microbes originate from the soil or from the leaf microbiome. Here, we disentangle the roles of soil origin, litter types and the microbial community already present on the leaf litter in determining fungal community composition on decomposing leaf litter and HFA. 2. We collected litters and associated soil samples from a secondary succession gradient ranging from herbaceous vegetation on recently abandoned ex‐arable fields to forest representing the end stage of succession. In a greenhouse, sterilized and unsterilized leaf litters were decomposed for 12 months in soils from early‐ to late‐successional stages according to a full‐factorial design. At the end, we examined fungal community composition on the decomposing litter. 3. Fungal communities on decomposed late‐successional litter in late‐successional soil differed from those in early‐ and mid‐successional stage litter and soil combinations. Soil source had the strongest impact on litter fungal composition when using sterilized litter, while the impact of litter type was strongest when using unsterilized litter. Overall, we observed HFA, as litter decomposition was accelerated in home soils. Increasing HFA did not relate to the dissimilarity in overall fungal composition, but there was increasing dissimilarity in the relative abundance of the most dominant fungal taxon between decomposing litter in home and away soils. 4. We conclude that early‐, mid‐ and late‐succession litter types did not exert strong selection effects on colonization by micro‐organisms from the soil species pool. Instead, fungal community composition on decomposing litter differed substantially between litter types for unsterilized litter, suggesting that the leaf microbiome, either directly or indirectly, is an important determinant of fungal community composition on decomposing leaves. HFA related most strongly to the abundance of the most dominant fungal taxa on the decomposing litter, suggesting that HFA may be attributed to some specific dominant fungi rather than to responses of the whole fungal community.Published versio

Competition and predation as possible causes of bacterial rarity

We assembled communities of bacteria and exposed them to different nutrient concentrations with or without predation by protists. Taxa that were rare in the field were less abundant at low nutrient concentrations than common taxa, independent of predation. However, some taxa that were rare in the field became highly abundant in the assembled communities, especially under ample nutrient availability. This high abundance points at a possible competitive advantage of some rare bacterial taxa under nutrient‐rich conditions. In contrast, the abundance of most rare bacterial taxa decreased at low resource availability. Since low resource availability will be the prevailing situation in most soils, our data suggests that under those conditions poor competitiveness for limiting resources may contribute to bacterial rarity. Interestingly, taxa that were rare in the field and most successful under predator‐free conditions in the lab also tended to be more reduced by predation than common taxa. This suggests that predation contributes to rarity of bacterial taxa in the field. We further discuss whether there may be a trade‐off between competitiveness and predation resistance. The substantial variability among taxa in their responses to competition and predation suggests that other factors, for example abiotic conditions and dispersal ability, also influence the local abundance of soil bacteria