| 41. |
- Jimenez, Javier, et al.
(författare)
-
Abnormally decreased NO and augmented CO production in islets of the leptin-deficient ob/ob mouse might contribute to explain hyperinsulinemia and islet survival in leptin-resistant type 2 obese diabetes.
- 2011
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 170, s. 43-51
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Tidskriftsartikel (refereegranskat)abstract
- The role of the gaseous messengers NO and CO for β-cell function and survival is controversial. We examined this issue in the hyperglycemic-hyperinsulinemic ob/ob mouse, an animal model of type 2 obese diabetes, by studying islets from obese vs lean mice regarding glucose-stimulated insulin release in relation to islet NO and CO production and the influence of modulating peptide hormones. Glucose-stimulated increase in ncNOS-activity in incubated lean islets was converted to a decrease in ob/ob islets associated with markedly increased insulin release. Both types of islet displayed iNOS activity appearing after ~60min in high-glucose. In ob/ob islets the insulinotropic peptides glucagon, GLP-1 and GIP suppressed NOS activities and amplified glucose-stimulated insulin release. The insulinostatic peptide leptin induced the opposite effects. Suppression of islet CO production inhibited, while stimulation amplified glucose-stimulated insulin release. Nonincubated isolated islets from young and adult obese mice displayed very low ncNOS and negligible iNOS activity. In contrast, production of CO, a NOS inhibitor, was impressively raised. Glucose injections induced strong activities of islet NOS isoforms in lean but not in obese mice and confocal microscopy revealed iNOS expression only in lean islets. Islets from ob/ob mice existing in a hyperglycemic in vivo milieu maintain elevated insulin secretion and protection from glucotoxicity through a general suppression of islet NOS activities achieved by leptin deficiency, high CO production and insulinotropic cyclic-AMP-generating hormones. Such a beneficial effect on islet function and survival might have its clinical counterpart in human leptin-resistant type 2 obese diabetes with hyperinsulinemia.
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| 42. |
- Jimenez, Javier, et al.
(författare)
-
Glucose stimulates the expression and activities of nitric oxide synthases in incubated rat islets: an effect counteracted by GLP-1 through the cyclic AMP/PKA pathway
- 2005
-
Ingår i: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 1432-0878 .- 0302-766X. ; 319:2, s. 221-230
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Tidskriftsartikel (refereegranskat)abstract
- We have examined the expression and activity of inducible nitric oxide synthase ( iNOS) and the activity of neuronal constitutive NOS ( ncNOS) in isolated rat pancreatic islets, stimulated by a "hyperglycaemic" concentration of glucose, and whether the NOS activities could be modulated by activation of the cyclic AMP/ protein kinase A ( cyclic AMP/PKA) system in relation to the insulin secretory process. Here, we show that glucose stimulation ( 20 mmol/l) induces iNOS and increases ncNOS activity. No iNOS is detectable at basal glucose levels (3.3 mmol/l). The addition of glucagon-like-peptide 1 (GLP-1) or dibutyryl-cAMP to islets incubated with 20 mmol/l glucose results in a marked suppression of iNOS expression and activity, a reduction in ncNOS activity and increased insulin release. The GLP-1-induced suppression of glucose-stimulated iNOS activity and expression and its stimulation of insulin release is, at least in part, PKA dependent, since the PKA inhibitor H-89 reverses the effects of GLP-1. These observations have been confirmed by confocal microscopy showing the glucose-stimulated expression of iNOS, its suppression by GLP-1 and its reversion by H-89 in beta-cells. We have also found that the NO scavenger cPTIO and the NOS inhibitor L-NAME potentiate the insulin response to glucose, again suggesting that NO is a negative modulator of glucose-stimulated insulin release. We conclude that the induction of iNOS and the increase in ncNOS activity caused by glucose in rat islets is suppressed by the cyclic AMP/ PKA system. The inhibition of iNOS expression by the GLP-1/ cyclic AMP/ PKA pathway might possibly be of therapeutic potential in NO-mediated beta-cell dysfunction and destruction.
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| 43. |
- Jimenez, Javier, et al.
(författare)
-
Insulin feedback actions: complex effects involving isoforms of islet nitric oxide synthase.
- 2004
-
Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 122:2, s. 109-118
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Tidskriftsartikel (refereegranskat)abstract
- The present study examined the effects of exogenous insulin on C-peptide release in relation to islet activities of neural constitutive nitric oxide synthase (ncNOS) and inducible NOS (iNOS). The dose–response curves for glucose-stimulated insulin and C-peptide release from isolated islets were practically identical: 0.05–0.1 nmol/l insulin stimulated, 1–100 nmol/l had no effect, whereas concentrations ≥250 nmol/l (“high insulin”), inhibited C-peptide release. Both the stimulatory and inhibitory effects were abolished by the phosphatidylinositol 3′-kinase inhibitor wortmannin. Addition of a NOS inhibitor partially reversed the inhibitory action of high insulin, but had no effect on the stimulatory action of low insulin (0.1 nmol/l). Moreover, high insulin markedly increased islet ncNOS activity and induced a strong iNOS activity. As shown biochemically and with confocal microscopy, the stimulatory action of high insulin on NOS activities and the associated inhibition of C-peptide release were reversed by raising cyclic AMP through addition of either glucagon-like peptide 1 (GLP-1) or dibutyryl cyclic AMP (Bt2cAMP) to the incubated islets. We conclude that the positive feedback mechanisms of action of insulin are independent of islet NOS activities and remain unclear. The negative feedback action of insulin, however, can be explained by its ability to stimulate both islet ncNOS activity and the expression and activity of iNOS. The effects on iNOS are most likely transduced through phosphatidylinositol 3′-kinase and are counteracted by raising islet cyclic AMP levels.
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| 44. |
- Jiménez-Navarro, Inmaculada C., et al.
(författare)
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Application of an integrated catchment-lake model approach for simulating effects of climate change on lake inputs and biogeochemistry
- 2023
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 885
-
Tidskriftsartikel (refereegranskat)abstract
- Climate change is simultaneously affecting lakes and their catchments, resulting in altered runoff patterns in the catchment and modified mixing and biogeochemical dynamics in lakes. The effects of climate change in a catchment will eventually have an impact on the dynamics of a downstream water body as well. An integrated model would allow considering how changes in the watershed affect the lake, but coupled modelling studies are rare. In this study we integrate a catchment model (SWAT+) and a lake model (GOTM-WET) to obtain holistic predictions for Lake Erken, Sweden. Using five different global climate models, projections of climate, catchment loads and lake water quality for the mid and end of the 21st century have been obtained under two future scenarios (SSP 2-45 and SSP 5-85). Temperature, precipitation and evapotranspiration will increase in the future, overall resulting in an increase in water inflow to the lake. An increasing importance of surface runoff will also have consequences on the catchment soil, hydrologic flow paths, and the input of nutrients to the lake. In the lake, water temperatures will rise, leading to increased stratification and a drop in oxygen levels. Nitrate levels are predicted to remain unchanged, while phosphate and ammonium levels increase. A coupled catchment-lake configuration such as that illustrated here allows prediction of future biogeochemical conditions of a lake, including linking land use changes to changing lake conditions, as well as eutrophication and browning studies. Since climate affects both the lake and the catchment, simulations of climate change should ideally take into account both systems.
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| 45. |
- Jiménez-Ortega, Elisa, et al.
(författare)
-
Implications of the Harmonization of [18F]FDG-PET/CT Imaging for Response Assessment of Treatment in Radiotherapy Planning
- 2022
-
Ingår i: Tomography. - : MDPI AG. - 2379-1381 .- 2379-139X. ; 8:2, s. 1097-1112
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of this work is to present useful recommendations for the use of [18F]FDG-PET/CT imaging in radiotherapy planning and monitoring under different versions of EARL accreditation for harmonization of PET devices. A proof-of-concept experiment designed on an anthropomorphic phantom was carried out to establish the most suitable interpolation methods of the PET images in the different steps of the planning procedure. Based on PET/CT images obtained by using these optimal interpolations for the old EARL accreditation (EARL1) and for the new one (EARL2), the treatment plannings of representative actual clinical cases were calculated, and the clinical implications of the resulting differences were analyzed. As expected, EARL2 provided smaller volumes with higher resolution than EARL1. The increase in the size of the reconstructed volumes with EARL1 accreditation caused high doses in the organs at risk and in the regions adjacent to the target volumes. EARL2 accreditation allowed an improvement in the accuracy of the PET imaging precision, allowing more personalized radiotherapy. This work provides recommendations for those centers that intend to benefit from the new accreditation, EARL2, and can help build confidence of those that must continue working under the EARL1 accreditation.
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| 46. |
- Jimenez, Tania, et al.
(författare)
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Rational Design and Experimental Analysis of Short-Oligonucleotide Substrate Specificity for Targeting Bacterial Nucleases
- 2021
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 64:17, s. 12855-12864
-
Tidskriftsartikel (refereegranskat)abstract
- An undecamer oligonucleotide probe based on a pair of deoxythymidines flanked by several modified nucleotides is a specific and highly efficient biosensor for micrococcal nuclease (MNase), an endonuclease produced by Staphylococcus aureus. Herein, the interaction mode and cleavage process on such oligonucleotide probes are identified and described for the first time. Also, we designed truncated pentamer probes as the minimum-length substrates required for specific and efficient biosensing. By means of computational (virtual docking) and experimental (ultra-performance liquid chromatography-mass spectrometry and matrix-assisted laser desorption ionization time-of-flight) techniques, we perform a sequence/structure-activity relationship analysis, propose a catalytically active substrate-enzyme complex, and elucidate a novel two-step phosphodiester bond hydrolysis mechanism, identifying the cleavage sites and detecting and quantifying the resulting probe fragments. Our results unravel a picture of both the enzyme-biosensor complex and a two-step cleavage/biosensing mechanism, key to the rational oligonucleotide design process.
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| 47. |
- Kiselev, Andrey, 1982-, et al.
(författare)
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Evaluation of using semi-autonomy features in mobile robotic telepresence systems
- 2015
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Ingår i: Proceedings of the 2015 7th IEEE International Conference on Cybernetics and Intelligent Systems, CIS 2015 and Robotics, Automation and Mechatronics, RAM 2015. - New York, USA : IEEE conference proceedings. - 9781467373388 ; , s. 147-152
-
Konferensbidrag (refereegranskat)abstract
- Mobile robotic telepresence systems used for social interaction scenarios require that users steer robots in a remote environment. As a consequence, a heavy workload can be put on users if they are unfamiliar with using robotic telepresence units. One way to lessen this workload is to automate certain operations performed during a telepresence session in order to assist remote drivers in navigating the robot in new environments. Such operations include autonomous robot localization and navigation to certain points in the home and automatic docking of the robot to the charging station. In this paper we describe the implementation of such autonomous features along with user evaluation study. The evaluation scenario is focused on the first experience on using the system by novice users. Importantly, that the scenario taken in this study assumed that participants have as little as possible prior information about the system. Four different use-cases were identified from the user behaviour analysis.
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| 48. |
- Langer, Judith, et al.
(författare)
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Present and Future of Surface-Enhanced Raman Scattering
- 2020
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-086X .- 1936-0851. ; 14:1, s. 28-117
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Forskningsöversikt (refereegranskat)abstract
- The discovery of the enhancement of Raman scattering by molecules adsorbed on nanostructured metal surfaces is a landmark in the history of spectroscopic and analytical techniques. Significant experimental and theoretical effort has been directed toward understanding the surface-enhanced Raman scattering (SERS) effect and demonstrating its potential in various types of ultrasensitive sensing applications in a wide variety of fields. In the 45 years since its discovery, SERS has blossomed into a rich area of research and technology, but additional efforts are still needed before it can be routinely used analytically and in commercial products. In this Review, prominent authors from around the world joined together to summarize the state of the art in understanding and using SERS and to predict what can be expected in the near future in terms of research, applications, and technological development. This Review is dedicated to SERS pioneer and our coauthor, the late Prof. Richard Van Duyne, whom we lost during the preparation of this article. ©
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| 49. |
- Liu, Kui, et al.
(författare)
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Kallikrein genes are associated with lupus and glomerular basement membrane-specific antibody-induced nephritis in mice and humans
- 2009
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 119:4, s. 911-923
-
Tidskriftsartikel (refereegranskat)abstract
- Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody-induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that maybe responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody-induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family,which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody-induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms,some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody-induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody-induced nephritis and lupus.
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| 50. |
- Lozano, Rodrigo, et al.
(författare)
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Adopting sustainability competence‐based education in academic disciplines: Insights from 13 higher education institutions
- 2022
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Ingår i: Sustainable Development. - : John Wiley & Sons. - 2160-7540 .- 2160-7559 .- 0968-0802 .- 1099-1719. ; 30:4, s. 620-635
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Tidskriftsartikel (refereegranskat)abstract
- Higher Education Institutions (HEIs) have been incorporating sustainability into education and curricula, where recent research has focussed on sustainability competences, pedagogical approaches, and how to connect them, generally on a single HEI. The process of integrating sustainability into education based on curricula assessment has been explained using adoption of innovations; and has the potential to explain the process of developing competences through pedagogical approaches. The aim of this paper is to investigate this process at academic discipline level. An online survey was developed to investigate teaching sustainability competences in 13 HEIs, from which 678 responses from educators were obtained. The competences and pedagogical approaches from the responses were ranked, and then the connections between the competences and pedagogical approaches per discipline were analysed using a correlations-based framework, from which three disciplines groups were created. The groups were categorised using diffusion of innovations theory, which indicated that some disciplines are more innovative than others in adopting sustainability competence-based teaching. The results are used to propose two frameworks to better understand the adoption of sustainability competence-based teaching: 1) the D-RAPID framework; and 2) the Disciplinary Multi-dimensional Sustainability Influence Change for Academia (D-MuSICA) memework. The adoption of sustainability competence-base education must expand from a single HEI perspective to a disciplinary collaborative one spanning many HEIs, where academic disciplines should learn from each other’s insights and mistakes and provide students with more transdisciplinary skillsets to make societies more sustainable.
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