| 1. |
- Areias, Filipe, et al.
(författare)
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2-Aryladenine Derivatives as a Potent Scaffold for Adenosine Receptor Antagonists : The 6-Morpholino Derivatives
- 2024
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Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 29:11
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Tidskriftsartikel (refereegranskat)abstract
- A set of 2-aryl-9-H or methyl-6-morpholinopurine derivatives were synthesized and assayed through radioligand binding tests at human A1, A2A, A2B, and A3 adenosine receptor subtypes. Eleven purines showed potent antagonism at A1, A3, dual A1/A2A, A1/A2B, or A1/A3 adenosine receptors. Additionally, three compounds showed high affinity without selectivity for any specific adenosine receptor. The structure-activity relationships were made for this group of new compounds. The 9-methylpurine derivatives were generally less potent but more selective, and the 9H-purine derivatives were more potent but less selective. These compounds can be an important source of new biochemical tools and/or pharmacological drugs.
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| 2. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 3. |
- Da Silva Carvalho, Ricardo Filipe
(författare)
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Mast cells in chronic inflammatory diseases : new insights in mast cell function and phenotype
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mast cells are multifunctional cells that play important roles in health and disease. They are long lived cells with the capacity to be activated several times. Upon activation mast cells release a huge array of mediators. The nature of the mediators released is dependent on the stimuli. The microenvironment in which the mast cell resides determines its phenotype and modulates its function. The aims of this thesis were to study the phenotype and role of mast cells in different chronic inflammatory diseases, particularly the importance of activation via CD30L/CD153 and the effects of hypoxia on mast cells. It has previously been shown that cells expressing CD30L can be activated by CD30 and that CD30 is associated with different inflammatory diseases, such as Hodgkin s lymphoma. Here we show that mast cells can be activated via CD30L with a CD30-Fc fusion protein, secreting chemokines in a degranulation-independent mechanism. We also provide evidence for an involvement of the MAPK and PI3K pathways in the signalling downstream of CD30L. Furthermore, we show that mast cells are the predominant CD30L expressing cells in atopic dermatitis and psoriasis and that IL-8 expressing mast cells are upregulated in lesional skin from both diseases. IL-8 secretion by mast cells was induced in CD30-treated healthy skin cultures. We next extended these findings to another chronic inflammatory disease, rheumatoid arthritis. In some studies mast cells have been implicated in the pathogenesis of the disease. The soluble form of CD30 is increased in the serum and synovial fluid of rheumatic patients, however there are no reports regarding the soluble form of CD30L in the serum or synovial fluid or the expression of CD30L in the synovium. We found a strong correlation between elevated levels of soluble CD30L in the serum and synovial fluid of patients suggesting a common origin for the molecule. A CD30L+ cell population was found in biopsies of the rheumatic synovium, but in contrast to what we observed in the first study, mast cells were not the CD30L predominant expressing cells. Hypoxic areas are found in different inflammatory conditions. In situations of low oxygen tension some cells die while others change their metabolism and adapt to the hypoxic condition. In the previous studies we discussed the involvement of mast cells in different chronic inflammatory diseases. In this study we show that mast cells regulate their survival to hypoxia in an autocrine way by secreting IL-6. In response to hypoxia, mast cells also secrete the proinflammatory cytokine TNF-alpha. Furthermore, we show that hypoxia does not affect degranulation and that the response to different activators is still sustained, although attenuated, under hypoxia when compared to normoxic conditions. These results suggest that mast cells are capable of resisting hypoxia and still respond to different stimuli even under hypoxic conditions, which can have important consequences in health and disease. In the last study presented in this thesis we validated the method used in previous studies and in the projects included in this thesis to identify human mast cells in vivo. Tryptase is the most abundant protein in mast cell granules and is frequently used as a mast cell marker in vivo. Here we show that different Hodgkin lymphoma cell lines also express tryptase in vitro. In vivo the tryptase expression is almost exclusively restricted to mast cells and the rare tryptase positive Hodgkin and Reed Stenberg cells are easily distinguished from mast cells by their characteristic morphology. In conclusion, this thesis elucidates some aspects of the function of mast cells in different chronic inflammatory diseases.
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| 4. |
- García-Palacios, Pablo, et al.
(författare)
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Crop traits drive soil carbon sequestration under organic farming
- 2018
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Ingår i: Journal of Applied Ecology. - Chichester : Wiley. - 0021-8901 .- 1365-2664. ; 55:5, s. 2496-2505
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Tidskriftsartikel (refereegranskat)abstract
- Organic farming (OF) enhances top soil organic carbon (SOC) stocks in croplands compared with conventional farming (CF), which can contribute to sequester C. As farming system differences in the amount of C inputs to soil (e.g. fertilization and crop residues) are not enough to explain such increase, shifts in crop residue traits important for soil C losses such as litter decomposition may also play a role. To assess whether crop residue (leaf and root) traits determined SOC sequestration responses to OF, we coupled a global meta-analysis with field measurements across a European-wide network of sites. In the meta-analysis, we related crop species averages of leaf N, leaf-dry matter content, fine-root C and N, with SOC stocks and sequestration responses in OF vs. CF. Across six European sites, we measured the management-induced changes in SOC stocks and leaf litter traits after long-term ecological intensive (e.g. OF) vs. CF comparisons. Our global meta-analysis showed that the positive OF-effects on soil respiration, SOC stocks, and SOC sequestration rates were significant even in organic farms with low manure application rates. Although fertilization intensity was the main driver of OF-effects on SOC, leaf and root N concentrations also played a significant role. Across the six European sites, changes towards higher leaf litter N in CF also promoted lower SOC stocks. Our results highlight that crop species displaying traits indicative of resource-acquisitive strategies (e.g. high leaf and root N) increase the difference in SOC between OF and CF. Indeed, changes towards higher crop residue decomposability was related with decreased SOC stocks under CF across European sites. Synthesis and applications. Our study emphasizes that, with management, changes in crop residue traits contribute to the positive effects of organic farming (OF) on soil carbon sequestration. These results provide a clear message to land managers: the choice of crop species, and more importantly their functional traits (e.g. leave and root nitrogen), should be considered in addition to management practices and climate, when evaluating the potential of OF for climate change mitigation.
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| 5. |
- Hernandez Alava, Monica, et al.
(författare)
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Measuring quality of life of patients with axial spondyloarthritis for economic evaluation
- 2022
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Ingår i: RMD Open. - : BMJ. - 2056-5933. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To estimate the relationship between EQ5D (three levels, UK version) and the Ankylosing Spondylitis Disease Activity Score (ASDAS) for use in the economic evaluation of health technologies for people with axial spondyloarthritis (axSpA). To compare against the relationship with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Methods An electronic, prospective, Portuguese, nationwide, rheumatic disease register (Reuma.pt) provided data on 1140 patients (5483 observations) with a confirmed diagnosis of axSpA. We estimated models of EQ5D as a function of ASDAS, alone or in combination with measures of functional impairment, using bespoke mixture models which reflect the complex distributional features of EQ5D. The SPondyloArthritis Caught Early cohort provided data from 344 patients (1405 observations) in four European countries and was used for validation. A previously published model of BASDAI/Bath Ankylosing Spondylitis Functional Index (BASFI) was also used to generate predicted EQ5D scores and model performance compared. Results A non-linear relationship exists between EQ5D from ASDAS. The final model included ASDAS, ASDAS squared, age and age squared and demonstrated close fit in both datasets except where data were sparse for patients with very high levels of disease activity (ASDAS >4). This finding held in the validation dataset. Models that included BASFI improved model fit. The ASDAS based models fit the data marginally less well than models using BASDAI. Conclusions Mapping models linking ASDAS to EQ5D allow results from clinical studies to be used in economic evaluation of health technologies with confidence. There is some loss of information compared with BASDAI but this has only a marginal impact.
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| 6. |
- Valencia-Montoya, Wendy A., et al.
(författare)
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Evolutionary trade-offs between male secondary sexual traits revealed by a phylogeny of the hyperdiverse tribe Eumaeini (Lepidoptera: Lycaenidae)
- 2021
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Ingår i: Proceedings of the Royal Society B: Biological Sciences. - : The Royal Society. - 1471-2954 .- 0962-8452. ; 288:1950
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Tidskriftsartikel (refereegranskat)abstract
- Male butterflies in the hyperdiverse tribe Eumaeini possess an unusually complex and diverse repertoire of secondary sexual characteristics involved in pheromone production and dissemination. Maintaining multiple sexually selected traits is likely to be metabolically costly, potentially resulting in trade-offs in the evolution of male signals. However, a phylogenetic framework to test hypotheses regarding the evolution and maintenance of male sexual traits in Eumaeini has been lacking. Here, we infer a comprehensive, time-calibrated phylogeny from 379 loci for 187 species representing 91% of the 87 described genera. Eumaeini is a monophyletic group that originated in the late Oligocene and underwent rapid radiation in the Neotropics. We examined specimens of 818 of the 1096 described species (75%) and found that secondary sexual traits are present in males of 91% of the surveyed species. Scent pads and scent patches on the wings and brush organs associated with the genitalia were probably present in the common ancestor of Eumaeini and are widespread throughout the tribe. Brush organs and scent pads are negatively correlated across the phylogeny, exhibiting a trade-off in which lineages with brush organs are unlikely to regain scent pads and vice versa. In contrast, scent patches seem to facilitate the evolution of scent pads, although they are readily lost once scent pads have evolved. Our results illustrate the complex interplay between natural and sexual selection in the origin and maintenance of multiple male secondary sexual characteristics and highlight the potential role of sexual selection spurring diversification in this lineage.
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| 7. |
- Vedovato, Laura B., et al.
(författare)
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Ancient fires enhance Amazon forest drought resistance
- 2023
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Ingår i: Frontiers in Forests and Global Change. - : Frontiers Media SA. - 2624-893X. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Drought and fire reduce productivity and increase tree mortality in tropical forests. Fires also produce pyrogenic carbon (PyC), which persists in situ for centuries to millennia, and represents a legacy of past fires, potentially improving soil fertility and water holding capacity and selecting for the survival and recruitment of certain tree life-history (or successional) strategies. We investigated whether PyC is correlated with physicochemical soil properties, wood density, aboveground carbon (AGC) dynamics and forest resistance to severe drought. To achieve our aim, we used an Amazon-wide, long-term plot network, in forests without known recent fires, integrating site-specific measures of forest dynamics, soil properties and a unique soil PyC concentration database. We found that forests with higher concentrations of soil PyC had both higher soil fertility and lower wood density. Soil PyC was not associated with AGC dynamics in non-drought years. However, during extreme drought events (10% driest years), forests with higher concentrations of soil PyC experienced lower reductions in AGC gains (woody growth and recruitment), with this drought-immunizing effect increasing with drought severity. Forests with a legacy of ancient fires are therefore more likely to continue to grow and recruit under increased drought severity. Forests with high soil PyC concentrations (third quartile) had 3.8% greater AGC gains under mean drought, but 33.7% greater under the most extreme drought than forests with low soil PyC concentrations (first quartile), offsetting losses of up to 0.68 Mg C ha–1yr–1 of AGC under extreme drought events. This suggests that ancient fires have legacy effects on current forest dynamics, by altering soil fertility and favoring tree species capable of continued growth and recruitment during droughts. Therefore, mature forest that experienced fires centuries or millennia ago may have greater resistance to current short-term droughts.
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| 8. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 9. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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