| 51. |
- Maeso-Alonso, Laura, et al.
(författare)
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p73 is required for vessel integrity controlling endothelial junctional dynamics through Angiomotin
- 2022
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Ingår i: Cellular and Molecular Life Sciences (CMLS). - : Springer Nature. - 1420-682X .- 1420-9071. ; 79:10
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Tidskriftsartikel (refereegranskat)abstract
- Preservation of blood vessel integrity, which is critical for normal physiology and organ function, is controlled at multiple levels, including endothelial junctions. However, the mechanism that controls the adequate assembly of endothelial cell junctions is not fully defined. Here, we uncover TAp73 transcription factor as a vascular architect that orchestrates transcriptional programs involved in cell junction establishment and developmental blood vessel morphogenesis and identify Angiomotin (AMOT) as a TAp73 direct transcriptional target. Knockdown of p73 in endothelial cells not only results in decreased Angiomotin expression and localization at intercellular junctions, but also affects its downstream function regarding Yes-associated protein (YAP) cytoplasmic sequestration upon cell-cell contact. Analysis of adherens junctional morphology after p73-knockdown in human endothelial cells revealed striking alterations, particularly a sharp increase in serrated junctions and actin bundles appearing as stress fibers, both features associated with enhanced barrier permeability. In turn, stabilization of Angiomotin levels rescued those junctional defects, confirming that TAp73 controls endothelial junction dynamics, at least in part, through the regulation of Angiomotin. The observed defects in monolayer integrity were linked to hyperpermeability and reduced transendothelial electric resistance. Moreover, p73-knockout retinas showed a defective sprout morphology coupled with hemorrhages, highlighting the physiological relevance of p73 regulation in the maintenance of vessel integrity in vivo. We propose a new model in which TAp73 acts as a vascular architect integrating transcriptional programs that will impinge with Angiomotin/YAP signaling to maintain junctional dynamics and integrity, while balancing endothelial cell rearrangements in angiogenic vessels.
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| 52. |
- Martín-Santamaría, Sonsoles, et al.
(författare)
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Symmetric dithiodigalactoside : strategic combination of binding studies and detection of selectivity between a plant toxin and human lectins
- 2011
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Ingår i: Organic and biomolecular chemistry. - : Royal Society of Chemistry (RSC). - 1477-0520 .- 1477-0539. ; 9:15, s. 5445-5455
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Tidskriftsartikel (refereegranskat)abstract
- Thioglycosides offer the advantage over O-glycosides to be resistant to hydrolysis. Based on initial evidence of this recognition ability for glycosyldisulfides by screening dynamic combinatorial libraries, we have now systematically studied dithiodigalactoside on a plant toxin (Viscum album agglutinin) and five human lectins (adhesion/growth-regulatory galectins with medical relevance e.g. in tumor progression and spread). Inhibition assays with surface-presented neoglycoprotein and in solution monitored by saturation transfer difference NMR spectroscopy, flanked by epitope mapping, as well as isothermal titration calorimetry revealed binding properties to VAA (K(a): 1560 +/- 20 M (1)). They were reflected by the structural model and the affinity on the level of toxin-exposed cells. In comparison, galectins were considerably less reactive, with intrafamily grading down to very minor reactivity for tandem-repeat-type galectins, as quantitated by radioassays for both domains of galectin-4. Model building indicated contact formation to be restricted to only one galactose moiety, in contrast to thiodigalactoside. The tested glycosyldisulfide exhibits selectivity between the plant toxin and the tested human lectins, and also between these proteins. Therefore, glycosyldisulfides have potential as chemical platform for inhibitor design.
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| 53. |
- Mesman, Jorrit P., 1993-, et al.
(författare)
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Timing of spring events changes under modelled future climate scenarios in a mesotrophic lake
- 2024
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Ingår i: Hydrology and Earth System Sciences. - : European Geosciences Union (EGU). - 1027-5606 .- 1607-7938. ; 28:8, s. 1791-1802
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Tidskriftsartikel (refereegranskat)abstract
- Lakes experience shifts in the timing of physical and biogeochemical events as a result of climate warming, and relative changes in the timing of events may have important ecological consequences. Spring, in particular, is a period in which many key processes that regulate the ecology and biogeochemistry of lakes occur and also a time that may experience significant changes under the influence of global warming. In this study, we used a coupled catchment–lake model forced by future climate projections to evaluate changes in the timing of spring discharge, ice-off, the spring phytoplankton peak, and the onset of stratification in a temperate mesotrophic lake. Although the model explained only part of the variation in these events, the overall patterns were simulated with little bias. All four events showed a clear trend towards earlier occurrence under climate warming, with ice cover tending to disappear at the end of the century in the most extreme climate scenario. Moreover, relative shifts in the timing of these springtime events also occurred, with the onset of stratification tending to advance more slowly than the other events and the spring phytoplankton peak and ice-off advancing faster in the most extreme climate scenario. The outcomes of this study stress the impact of climate change on the phenology of events in lakes and especially the relative shifts in timing during spring. This can have profound effects on food web dynamics as well as other regulatory processes and influence the lake for the remainder of the growing season.
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| 54. |
- Mora-Salgueiro, Javier, et al.
(författare)
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The Prevalence and Clinical and Sociodemographic Factors of Problem Online Gambling : A Systematic Review
- 2021
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Ingår i: Journal of Gambling Studies. - : Springer Nature. - 1050-5350 .- 1573-3602. ; 37:3, s. 899-926
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Tidskriftsartikel (refereegranskat)abstract
- The emergence and spread of new technologies have allowed for the introduction of new forms of gambling. Problem online gambling has specific characteristics, and its prevalence may differ from traditional forms of gambling. This paper systematically reviews studies that include data relevant to problem online gambling and to the sociodemographic and comorbidity variables related to it. A systematic literature search was conducted from Medline database. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, preliminary search resulted in 427 articles, from which 20 were included in this systematic review based on pre-determined criteria. The reported prevalence of problem online gambling varied widely across the different studies. This heterogeneity is due to large variations in settings, instruments, and definitions of problem online gambling, which rules out a meta-analytic approach to the results. The sources of variability in the prevalence, the sociodemographic and comorbidity factors, and the implications for future research are discussed.
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| 55. |
- Mosén, Henrik, et al.
(författare)
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Defective glucose-stimulated insulin release in the diabetic Goto-Kakizaki (GK) rat coincides with reduced activity of the islet carbon monoxide signaling pathway
- 2005
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 146:3, s. 1553-1558
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Tidskriftsartikel (refereegranskat)abstract
- The Goto-Kakizaki (GK) rat displays a markedly reduced insulin response to glucose, a defect that is thought to be coupled to an impaired glucose signaling in the beta-cell. We have examined whether carbon monoxide (CO), derived from beta-cell heme oxygenase (HO), might be involved in the secretory dysfunction. Immunocytochemical labeling of constitutive HO (HO-2) showed no overt difference in fluorescence pattern in islets from GK vs. Wistar controls. However, isolated islets from GK rats displayed a markedly impaired HO activity measured as CO production (-50%), and immunoblotting revealed an approximately 50% reduction of HO-2 protein expression compared with Wistar controls. Furthermore, there was a prominent expression of inducible HO (HO-1) in GK islets. Incubation of isolated islets showed that the glucose-stimulated CO production and the glucose-stimulated insulin response were considerably reduced in GK islets compared with Wistar islets. Addition of the HO activator hemin or gaseous CO to the incubation media brought about a similar amplification of glucose-stimulated insulin release in GK and Wistar islets, suggesting that distal steps in the HO-CO signaling pathway were not appreciably affected. We conclude that the defective insulin response to glucose in the GK rat can be explained, at least in part, by a marked impairment of the glucose-HO-CO signaling pathway as manifested by a prominent decrease in glucose stimulation of islet CO production and a reduced expression of HO-2. A possible role of HO-1 expression as a compensatory mechanism in the GK islets is presently unclear.
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| 56. |
- Mosén, Henrik, et al.
(författare)
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Impaired glucose-stimulated insulin secretion in the GK rat is associated with abnormalities in islet nitric oxide production.
- 2008
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 151, s. 139-146
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Tidskriftsartikel (refereegranskat)abstract
- We investigated implications of nitric oxide (NO) derived from islet neuronal constitutive NO synthase (ncNOS) and inducible NOS (iNOS) on insulin secretory mechanisms in the mildly diabetic GK rat. Islets from GK rats and Wistar controls were analysed for ncNOS and iNOS by HPLC, immunoblotting and immunocytochemistry in relation to insulin secretion stimulated by glucose or l-arginine in vitro and in vivo. No obvious difference in ncNOS fluorescence in GK vs control islets was seen but freshly isolated GK islets displayed a marked iNOS expression and activity. After incubation at low glucose GK islets showed an abnormal increase in both iNOS and ncNOS activities. At high glucose the impaired glucose-stimulated insulin release was associated with an increased iNOS expression and activity and NOS inhibition dose-dependently amplified insulin secretion in both GK and control islets. This effect by NOS inhibition was also evident in depolarized islets at low glucose, where forskolin had a further amplifying effect in GK but not in control islets. NOS inhibition increased basal insulin release in perfused GK pancreata and amplified insulin release after glucose stimulation in both GK and control pancreata, almost abrogating the nadir separating first and second phase in controls. A defective insulin response to l-arginine was seen in GK rats in vitro and in vivo, being partially restored by NOS inhibition. The results suggest that increased islet NOS activities might contribute to the defective insulin response to glucose and l-arginine in the GK rat. Excessive iNOS expression and activity might be deleterious for the beta-cells over time.
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| 57. |
- Moyano-Cambero, Carles E., et al.
(författare)
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Petrographic and geochemical evidence for multiphase formation of carbonates in the Martian orthopyroxenite Allan Hills 84001
- 2017
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Ingår i: Meteoritics and Planetary Science. - : John Wiley & Sons. - 1086-9379 .- 1945-5100. ; 52:6, s. 1030-1047
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Tidskriftsartikel (refereegranskat)abstract
- Martian meteorites can provide valuable information about past environmental conditions on Mars. Allan Hills 84001 formed more than 4 Gyr ago, and owing to its age and long exposure to the Martian environment, and this meteorite has features that may record early processes. These features include a highly fractured texture, gases trapped during one or more impact events or during formation of the rock, and spherical Fe-Mg-Ca carbonates. In this study, we have concentrated on providing new insights into the context of these carbonates using a range of techniques to explore whether they record multiple precipitation and shock events. The petrographic features and compositional properties of these carbonates indicate that at least two pulses of Mg- and Fe-rich solutions saturated the rock. Those two generations of carbonates can be distinguished by a very sharp change in compositions, from being rich in Mg and poor in Fe and Mn, to being poor in Mg and rich in Fe and Mn. Between these two generations of carbonate is evidence for fracturing and local corrosion
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| 58. |
- Nylander, S., et al.
(författare)
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A complementing approach for identifying ethical issues in care robotics - Grounding ethics in practical use
- 2012
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Ingår i: RO-MAN, 2012 IEEE. - : IEEE. - 9781467346054 ; , s. 797-802, s. 797-802
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Konferensbidrag (refereegranskat)abstract
- We use a long-term study of a robotic eating-aid for disabled users to illustrate how empirical use give rise to a set of ethical issues that might be overlooked in ethic discussions based on theoretical extrapolation of the current state-of-the-art in robotics. This approach provides an important complement to the existing robot ethics by revealing new issues as well as providing actionable guidance for current and future robot design. We discuss our material in relation to the literature on robot ethics, specifically the risk of robots performing care taking tasks and thus causing increased isolation for care recipients. Our data identifies a different set of ethical issues such as independence, privacy, and identity where robotics, if carefully designed and developed, can make positive contributions.
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| 59. |
- Orlandini, Andrea, et al.
(författare)
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ExCITE Project : A Review of Forty-Two Months of Robotic Telepresence Technology
- 2016
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Ingår i: Presence - Teleoperators and Virtual Environments. - Cambridge, USA : MIT Press. - 1054-7460 .- 1531-3263. ; 25:3, s. 204-221
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Tidskriftsartikel (refereegranskat)abstract
- This article reports on the EU project ExCITE with specific focus on the technical development of the telepresence platform over a period of 42 months. The aim of the project was to assess the robustness and validity of the mobile robotic telepresence (MRP) system Giraff as a means to support elderly people and to foster their social interaction and participation. Embracing the idea of user-centered product refinement, the robot was tested over long periods of time in real homes. As such, the system development was driven by a strong involvement of elderly people and their caregivers but also by technical challenges associated with deploying the robot in real-world contexts. The results of the 42-months’ long evaluation is a system suitable for use in homes rather than a generic system suitable, for example, in office environments.
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| 60. |
- Qader, Saleem, et al.
(författare)
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Expression of islet iNOS and inhibition of glucose stimulated insulin release after long-term lipid infusion in the rat is counteracted by PACAP27.
- 2007
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Ingår i: American Journal of Physiology: Endocrinology and Metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 292:5, s. 1447-1455
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Tidskriftsartikel (refereegranskat)abstract
- Chronic exposure of pancreatic islets to elevated plasma lipids ( lipotoxicity) can lead to beta-cell dysfunction, with overtime becoming irreversible. We examined, by confocal microscopy and biochemistry, whether the expression of islet inducible nitric oxide synthase ( iNOS) and the concomitant inhibition of glucose-stimulated insulin release seen after lipid infusion in rats was modulated by the islet neuropeptide pituitary adenylate cyclase-activating polypeptide ( PACAP) 27. Lipid infusion for 8 days induced a strong expression of islet iNOS, which was mainly confined to beta-cells and was still evident after incubating islets at 8.3 mmol/l glucose. This was accompanied by a high iNOS-derived NO generation, a decreased insulin release, and increased cyclic GMP accumulation. No iNOS expression was found in control islets. Addition of PACAP27 to incubated islets from lipid-infused rats resulted in loss of iNOS protein expression, increased cyclic AMP, decreased cyclic GMP, and suppression of the activities of neuronal constitutive ( nc) NOS and iNOS and increased glucose-stimulated insulin response. These effects were reversed by the PKA inhibitor H-89. The suppression of islet iNOS expression induced by PACAP27 was not affected by the proteasome inhibitor MG-132, which by itself induced the loss of iNOS protein, making a direct proteasomal involvement less likely. Our results suggest that PACAP27 through its cyclic AMP- and PKA-stimulating capacity strongly suppresses not only ncNOS but, importantly, also the lipid-induced stimulation of iNOS expression, possibly by a nonproteasomal mechanism. Thus PACAP27 restores the impairment of glucose-stimulated insulin release and additionally might induce cytoprotection against deleterious actions of iNOS-derived NO in beta-cells.
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