| 1. |
- Lötvall, Jan, 1956, et al.
(författare)
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24-h duration of the novel LABA vilanterol trifenatate in asthma patients treated with inhaled corticosteroids
- 2012
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 40:3, s. 570-579
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Tidskriftsartikel (refereegranskat)abstract
- Current guidelines recommend adding a long-acting inhaled beta(2)-agonist (LABA) to inhaled corticosteroids (ICS) in patients with uncontrolled asthma. This study evaluated the novel, once-daily LABA vilanterol trifenatate (VI) in asthma patients who remained symptomatic despite existing ICS therapy. The study involved a randomised, double-blind, placebo-controlled trial of VI (3, 6.25, 12.5, 25 and 50 mu g), administered once daily in the evening by dry powder inhaler for 28 days, in asthma patients aged >= 12 yrs symptomatic on current ICS therapy. The primary end-point was trough (24 h post-dose) forced expiratory volume in 1 s (FEV1); secondary end-points were weighted mean FEV1, peak expiratory flow (PEF), symptom-/rescue-free 24-h periods, and safety. A significant relationship was observed between VI dose and improvements in trough FEV1 (p=0.037). Statistically significant increases in mean trough FEV1, relative to placebo, were documented for VI 12.5-50 mu g (121-162 mL; p <= 0.016). Dose-related effects of VI were observed on weighted mean (0-24 h) FEV1, morning/evening PEF, and symptom-/rescue-free 24-h periods. All doses of VI were well tolerated with low incidences of recognised LABA-related adverse events (tremor 0-2%; palpitations 0-2%; glucose effects 0-1%; potassium effects 0-<1%). Once-daily VI 12.5-50 mu g resulted in prolonged bronchodilation of at least 24 h with good tolerability in asthma patients receiving ICS. Based on the overall efficacy and adverse event profile from this study, the optimum dose of VI appears to be 25 mg.
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| 2. |
- Casey, John R., et al.
(författare)
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Basin-scale biogeography of marine phytoplankton reflects cellular-scale optimization of metabolism and physiology
- 2022
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Ingår i: Science advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:3
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Tidskriftsartikel (refereegranskat)abstract
- Extensive microdiversity within Prochlorococcus, the most abundant marine cyanobacterium, occurs at scales from a single droplet of seawater to ocean basins. To interpret the structuring role of variations in genetic potential, as well as metabolic and physiological acclimation, we developed a mechanistic constraint-based modeling framework that incorporates the full suite of genes, proteins, metabolic reactions, pigments, and biochemical compositions of 69 sequenced isolates spanning the Prochlorococcus pangenome. Optimizing each strain to the local, observed physical and chemical environment along an Atlantic Ocean transect, we predicted variations in strain-specific patterns of growth rate, metabolic configuration, and physiological state, defining subtle niche subspaces directly attributable to differences in their encoded metabolic potential. Predicted growth rates covaried with observed ecotype abundances, affirming their significance as a measure of fitness and inferring a nonlinear density dependence of mortality. Our study demonstrates the potential to interpret global-scale ecosystem organization in terms of cellular-scale processes.
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| 3. |
- Dutkiewicz, Stephanie, et al.
(författare)
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Multiple biotic interactions establish phytoplankton community structure across environmental gradients
- 2024
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Ingår i: Limnology and Oceanography. - : John Wiley & Sons. - 0024-3590 .- 1939-5590.
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Tidskriftsartikel (refereegranskat)abstract
- The combination of taxa and size classes of phytoplankton that coexist at any location affects the structure of the marine food web and the magnitude of carbon fluxes to the deep ocean. But what controls the patterns of this community structure across environmental gradients remains unclear. Here, we focus on the North East Pacific Transition Zone, a similar to 10 degrees region of latitude straddling warm, nutrient-poor subtropical and cold, nutrient-rich subpolar gyres. Data from three cruises to the region revealed intricate patterns of phytoplankton community structure: poleward increases in the number of cell size classes; increasing biomass of picoeukaryotes and diatoms; decreases in diazotrophs and Prochlorococcus; and both increases and decreases in Synechococcus. These patterns can only be partially explained by existing theories. Using data, theory, and numerical simulations, we show that the patterns of plankton distributions across the transition zone are the result of gradients in nutrient supply rates, which control a range of complex biotic interactions. We examine how interactions such as size-specific grazing, multiple trophic strategies, shared grazing between several phytoplankton size classes and heterotrophic bacteria, and competition for multiple resources can individually explain aspects of the observed community structure. However, it is the combination of all these interactions together that is needed to explain the bulk compositional patterns in phytoplankton across the North East Pacific Transition Zone. The synthesis of multiple mechanisms is essential for us to begin to understand the shaping of community structure over large environmental gradients.
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| 4. |
- Follows, D, et al.
(författare)
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beta-Casein adsorption at the silicon oxide-aqueous solution interface: Calcium ion effects
- 2004
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1526-4602 .- 1525-7797. ; 5:2, s. 319-325
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Tidskriftsartikel (refereegranskat)abstract
- Neutron reflectometry was used to investigate effects of calcium ions on the interfacial behavior of beta-casein at the silicon oxide-aqueous solution interface. The structural characteristics of the adsorbed layer were determined from reflectivity curves fitted to three- and two-layer optical models. The results showed that the presence of divalent calcium ions decreased the specific electrostatic adsorption affinity of the protein to silica compared with the calcium-free buffer system studied in an earlier work. In addition, it speeded up the adsorption suggesting that the slow kinetics seen in the calcium-free system are related to conformational adjustments of the beta-casein structure driven by the maximization of the number of positive charges on the polypeptide interacting with negative surface charges. In the calcium-free system, a dense inner layer resulted from this process, with cationic segments firmly bound to the negative surface, whereas in the presence of calcium, a less dense inner layer was formed. The difference in binding is also mirrored by the effects on the interfacial layer of a specific proteolytic enzyme, i.e., endoproteinase Asp-N. In the calcium-free case, an inner dense layer remained at the surface after the proteolytic cleavage of the polypeptide, whereas virtually nothing was left after enzymatic action in the presence of calcium ions.
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| 5. |
- Follows, D., et al.
(författare)
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Multilayers at the surface of solutions of exogenous lung surfactant: Direct observation by neutron reflection
- 2007
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Ingår i: Biochimica et Biophysica Acta - Biomembranes. - : Elsevier BV. - 0005-2736. ; 1768:2, s. 228-235
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Tidskriftsartikel (refereegranskat)abstract
- Pharmacy-grade exogenous lung surfactant preparations of bovine and porcine origin, dispersed in physiological electrolyte solution have been studied. The organization and dynamics at the air/water interface at physiological temperature was analysed by neutron reflection. The results show that a well-defined surface phase is formed, consisting of a multilayer structure of lipid/protein bilayers alternating with aqueous layers, with a repetition period of about 70 A and correlation depths of 3 to > 25 bilayers, depending on electrolyte composition and time. The experimental surfactant concentration of 0.15% (w/w) is far below that used in therapeutic application of exogenous surfactants and it is therefore likely that similar multilayer structures are also formed at the alveolar surface in the clinical situation during surfactant substitution therapy. Lung surfactant preparations in dry form swell in aqueous solution towards a limit of about 60% (w/w) of water, forming a lamellar liquid-crystalline phase above about 34 degrees C, which disperses into lamellar bodies at higher water concentrations. The lamellar spacings in the surface multilayers at the air/water interface are smaller than those in the saturated limit even though they are in contact with much greater water concentrations. The surface multilayers are laterally disordered in a way that is consistent with fragments of La-phase lamellae. The near surface layers of the multilayer structure have a significant protein content (only SP-B and SP-C are present in the preparations). The results demonstrate that a multilayer structure can be formed in exogenous surfactant even at very low concentrations and indicate that multilayers need to be incorporated into present interpretations of in vitro studies of similar lung surfactant preparations, which are largely based on monolayer models. (c) 2006 Elsevier B.V All rights reserved.
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| 6. |
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