| 1. |
- Abraham-Nordling, Mirna, et al.
(författare)
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Incidence of hyperthyroidism in Sweden
- 2011
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 165:6, s. 899-905
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The incidence of hyperthyroidism has been reported in various countries to be 23-93/100000 inhabitants per year. This extended study has evaluated the incidence for similar to 40% of the Swedish population of 9 million inhabitants. Sweden is considered to be iodine sufficient country. Methods:All patients including children, who were newly diagnosed with overt hyperthyroidism in the years 2003-2005, were prospectively registered in a multicenter study. The inclusion criteria are as follows:clinical symptoms and/or signs of hyperthyroidism with plasma TSH concentration below 0.2 mIE/l and increased plasma levels of free/total triiodothyronine and/or free/total thyroxine. Patients with relapse of hyperthyroidism or thyroiditis were not included. The diagnosis of Graves' disease (GD), toxic multinodular goiter (TMNG) and solitary toxic adenoma (STA), smoking, initial treatment, occurrence of thyroid-associated eye symptoms/signs, and demographic data were registered. Results:A total of 2916 patients were diagnosed with de novo hyperthyroidism showing the total incidence of 27.6/100 000 inhabitants per year. The incidence of GD was 21.0/100 000 and toxic nodular goiter (TNG=STA+TMNG) occurred in 692 patients, corresponding to an annual incidence of 6.5/100 000. The incidence was higher in women compared with men (4.2:1). Seventy-five percent of the patients were diagnosed with GD, in whom thyroid-associated eye symptoms/signs occurred during diagnosis in every fifth patient. Geographical differences were observed. Conclusion:The incidence of hyperthyroidism in Sweden is in a lower range compared with international reports. Seventy-five percent of patients with hyperthyroidism had GD and 20% of them had thyroid-associated eye symptoms/signs during diagnosis. The observed geographical differences require further studies.
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| 2. |
- Brante, Thomas, et al.
(författare)
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Profession och vetenskap : idéer och strategier för ett professionslärosäte
- 2009
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Förord av Björn Brorström, Prorektor Högskolan i Borås Ett professionslärosäte bedriver utbildning och forskning på vetenskaplig grund. Vetenskapliga metoder tillämpas och framkomna resultat prövas för att säkra tillförlitlighet och relevans. Förmågan att problematisera, formulera frågor och välja lämpliga metoder för att besvara frågor är egenskaper för god forskning och utmärkande för en stark utbildnings- och forskningsmiljö. Vid ett professionslärosäte finns samtidigt en stark strävan efter att i utbildning och forskning ta till vara den kunskap och de erfarenheter som professioner besitter och därigenom säkra en hög grad av praktisk relevans. Växelverkan mellan teori och praktik och erfarenhetsutbyte mellan forskare och praktiker är ständigt pågående. Det finns ingen avslutning på processen utan den pågår utan avbrott. En nödvändig förutsättning för ett fruktbart samarbete är en ömsesidig respekt och vilja att stödja och ifrågasätta varandra. Forskaren måste vara beredd på kritik för bristen på praktisk relevans och professionsföreträdaren måste vara beredd på att förtrogenhetskunskapens lämplighet ifrågasätts. Det är en fråga om med- och mothåll från båda håll i syfte att långsiktigt utveckla teori och praktik. Det är en utmaning att utveckla, etablera och därefter kontinuerligt försvara och förbättra professionslärosätet. Ett led i utvecklingen är att inom ramen för Högskolan i Borås föra en debatt om innebörden av ett professionslärosäte och vad vi behöver göra för att förbättra verksamheten. På uppdrag av rektor Lena Nordholm har medarbetare vid Bibliotekshögskolan utvecklat och ansvarat för en seminarieserie benämnd Profession och vetenskap. Seminarierna spände över ett brett fält. En av många viktiga frågor som diskuterades flitigt var huruvida vi ska forska om professioner, i för eller med, eller kanske alltihop samtidigt. Bidragen publiceras nu i denna antologi som ges ut inom ramen för Högskolan i Borås rapportserie Vetenskap för profession. Rapporten Profession och vetenskap – idéer och strategier för ett professionslärosäte, som redigerats av universitetsadjunkt Maria Lindh, kommer att få stor betydelse inom lärosätet och i vårt samarbete med företrädare för näringsliv, kulturliv och offentlig verksamhet. Jag ser det som en intressant fortsättning att anordna ett antal seminarier med inbjudna representanter för professioner där artiklarna i denna rapport kan ligga till grund för erfarenhetsutbyte och diskussioner.
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| 3. |
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| 4. |
- Fredriksson, Åsa, 1968, et al.
(författare)
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Decline in ribosomal fidelity contributes to the accumulation and stabilization of the master stress response regulator sigma S upon carbon starvation
- 2007
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Ingår i: Genes & Development. - : Cold Spring Harbor Laboratory. - 0890-9369 .- 1549-5477. ; 21:7, s. 862-874
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Tidskriftsartikel (refereegranskat)abstract
- The {sigma}S subunit of RNA polymerase is a master regulator of Escherichia coli that retards cellular senescence and bestows cells with general stress protective functions during growth arrest. We show that mutations and drugs triggering translational errors elevate {sigma}S levels and stability. Furthermore, mutations enhancing translational fidelity attenuate induction of the rpoS regulon and prevent stabilization of {sigma}S upon carbon starvation. Destabilization of {sigma}S by increased proofreading requires the presence of the {sigma}S recognition factor SprE (RssB) and the ClpXP protease. The data further suggest that {sigma}S becomes stabilized upon starvation as a result of ClpP sequestration and this sequestration is enhanced by oxidative modifications of aberrant proteins produced by erroneous translation. ClpP overproduction counteracted starvation-induced stabilization of {sigma}S, whereas overproduction of a ClpXP substrate (ssrA-tagged GFP) stabilized {sigma}S in exponentially growing cells. We present a model for the sequence of events leading to the accumulation and activation of {sigma}S upon carbon starvation, which are linked to alterations in both ribosomal fidelity and efficiency.
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| 5. |
- Gericke, Martin, et al.
(författare)
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The European Polysaccharide Network of Excellence (EPNOE) research roadmap 2040: Advanced strategies for exploiting the vast potential of polysaccharides as renewable bioresources
- 2024
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Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617 .- 1879-1344. ; 326
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Tidskriftsartikel (refereegranskat)abstract
- Polysaccharides are among the most abundant bioresources on earth and consequently need to play a pivotal role when addressing existential scientific challenges like climate change and the shift from fossil-based to sustainable biobased materials. The Research Roadmap 2040 of the European Polysaccharide Network of Excellence (EPNOE) provides an expert's view on how future research and development strategies need to evolve to fully exploit the vast potential of polysaccharides as renewable bioresources. It is addressed to academic researchers, companies, as well as policymakers and covers five strategic areas that are of great importance in the context of polysaccharide related research: (I) Materials & Engineering, (II) Food & Nutrition, (III) Biomedical Applications, (IV) Chemistry, Biology & Physics, and (V) Skills & Education. Each section summarizes the state of research, identifies challenges that are currently faced, project achievements and developments that are expected in the upcoming 20 years, and finally provides outlines on how future research activities need to evolve.
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| 6. |
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| 11. |
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| 13. |
- Vercalsteren, Ellen, et al.
(författare)
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The SGLT2 inhibitor Empagliflozin promotes post-stroke functional recovery in diabetic mice
- 2024
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Ingår i: Cardiovascular Diabetology. - 1475-2840. ; 23
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Tidskriftsartikel (refereegranskat)abstract
- Type-2 diabetes (T2D) worsens stroke recovery, amplifying post-stroke disabilities. Currently, there are no therapies targeting this important clinical problem. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are potent anti-diabetic drugs that also efficiently reduce cardiovascular death and heart failure. In addition, SGLT2i facilitate several processes implicated in stroke recovery. However, the potential efficacy of SGLT2i to improve stroke recovery in T2D has not been investigated. Therefore, we determined whether a post-stroke intervention with the SGLT2i Empagliflozin could improve stroke recovery in T2D mice. T2D was induced in C57BL6J mice by 8 months of high-fat diet feeding. Hereafter, animals were subjected to transient middle cerebral artery occlusion and treated with vehicle or the SGLTi Empagliflozin (10 mg/kg/day) starting from 3 days after stroke. A similar study in non diabetic mice was also conducted. Stroke recovery was assessed using the forepaw grip strength test. To identify potential mechanisms involved in the Empagliflozin-mediated effects, several metabolic parameters were assessed. Additionally, neuronal survival, neuroinflammation, neurogenesis and cerebral vascularization were analyzed using immunohistochemistry/quantitative microscopy. Empagliflozin significantly improved stroke recovery in T2D but not in non-diabetic mice. Improvement of functional recovery was associated with lowered glycemia, increased serum levels of fibroblast growth factor-21 (FGF-21), and the normalization of T2D-induced aberration of parenchymal pericyte density. The global T2D-epidemic and the fact that T2D is a major risk factor for stroke are drastically increasing the number of people in need of efficacious therapies to improve stroke recovery. Our data provide a strong incentive for the potential use of SGLT2i for the treatment of post-stroke sequelae in T2D.
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| 14. |
- Adolfsson, Caroline, et al.
(författare)
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Collaborative introspection as a methodological tool of reflexivity - from multidisciplinary to transdisciplinary co-production
- 2021
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Ingår i: International Transdisciplinarity Conference (ITD21), 13-17 Sept: Creating spaces and cultivating mindsets for learning and experimentation.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- This paper explores reflexivity through "collaborative introspection" as a methodological tool for transcending a multidisciplinary dialogue and achieving transdisciplinary co-production of knowledge. Reflexivity is argued to be applicable for critically addressing assumptions and ideologies of the research team (Popa et al., 2015), joint problem framing (Pearce & Ejderyan, 2019), experimentation (Popa et al., 2015), or more generally as a focal area to be used for addressing challenges in transdisciplinary projects (Jahn, et al., 2012; Polk, 2015). However, discussions on reflexivity rarely place focus on how a reflexive dialogue can be used to gather empirical material in a collaborative manner, making use of the participating researchers’ subjectivity, personal experiences and understandings of a specific topic. The authors of this text are part of a transdisciplinary research team exploring the role of tourism in multicultural societies. The team involves researchers from the fields of design, marketing, tourism studies, human-computer interaction, and migration studies. In the project we collaborate with each other across disciplines in different case studies. However, we have experienced a tendency to fall back into our disciplinary silos, where we explore the same topic from our own disciplinary lenses. As an attempt to bring ourselves together we decided to go personal. Instead of looking at the role of tourism in multicultural societies from our disciplinary viewpoints, we dug into our memories of acting as tourists ourselves in a reflective session. More specifically, inspired by the tool Tell your story by means of an object (td-net, 2021), we shared and reflected upon our own tourism experiences through our core project concepts, which are diversity, inclusivity and integration. The dialogue that emerged forced us to focus on our research topic not as researchers who are expected to maintain objectivity but rather as individuals allowing ourselves to be subjective. This created a feeling of working ‘together’ instead of ‘with’ each other. The reflections created genuine and honest dialogue highlighting our national, cultural, gender and racial differences. The differences and similarities of our personal experiences depend on the social categories and identities that we are part of. Thus, by bringing our personal stories as empirical material, we created an opportunity to listen to each other beyond our disciplinary boundaries. It made us understand the layers of hierarchy, privilege and disadvantages that we face in our lives as individuals, and to understand instances of inclusion and exclusion in tourism at a deeper level. From our experience, we propose what we term "collaborative introspection" as a reflexive methodological tool for transdisciplinary research and practice. Collaborative introspection exercises challenge the commonly held idea of neutrality. It can be used as a tool for a transdisciplinary group to come together, transform thoughts and develop empathy and ethics in research. References: Jahn, T., Bergmann, M. & Keil, F. (2018). Transdisciplinarity: between mainstreaming and marginalization, Ecological Economics 79 Pearce, B. J., & Ejderyan, O. (2020). Joint problem framing as reflexive practice: honing a transdisciplinary skill. Sustainability science, 15(3), 683-698. Polk, M. (2015). Transdisciplinary co-production: Designing and testing a transdisciplinary research framework for societal problem solving. Futures, 65, 110-122. Popa, F., Guillermin, M., & Dedeurwaerdere, T. (2015). A pragmatist approach to transdisciplinarity in sustainability research: From complex systems theory to reflexive science. Futures, 65, 45-56. Td-net (2021, April 7). Tell your Story by Means of an Object. Retrieved from: https://naturalsciences.ch/co-producing-knowledge-explained/methods/td-net_toolbox/_tell_your_story_by_means_of_an_object_
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| 15. |
- Aertsen, A., et al.
(författare)
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Heat shock protein-mediated resistance to high hydrostatic pressure in Escherichia coli
- 2004
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Ingår i: Applied and Environmental Microbiology. - 0099-2240. ; 70:5, s. 2660-2666
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Tidskriftsartikel (refereegranskat)abstract
- A random library of Escherichia coli MG1655 genomic fragments fused to a promoterless green fluorescent protein (GFP) gene was constructed and screened by differential fluorescence induction for promoters that are induced after exposure to a sublethal high hydrostatic pressure stress. This screening yielded three promoters of genes belonging to the heat shock regulon (dnaK, lon, clpPX), suggesting a role for heat shock proteins in protection against, and/or repair of, damage caused by high pressure. Several further observations provide additional support for this hypothesis: (i) the expression of rpoH, encoding the heat shock-specific sigma factor {sigma}32, was also induced by high pressure; (ii) heat shock rendered E. coli significantly more resistant to subsequent high-pressure inactivation, and this heat shock-induced pressure resistance followed the same time course as the induction of heat shock genes; (iii) basal expression levels of GFP from heat shock promoters, and expression of several heat shock proteins as determined by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis of proteins extracted from pulse-labeled cells, was increased in three previously isolated pressure-resistant mutants of E. coli compared to wild-type levels.
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| 16. |
- Ahmadpour, Doryaneh, 1973, et al.
(författare)
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Hitchhiking on vesicles: a way to harness age-related proteopathies?
- 2020
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Ingår i: FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 287:23, s. 5068-5079
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Tidskriftsartikel (refereegranskat)abstract
- Central to proteopathies and leading to most age-related neurodegenerative disorders is a failure in protein quality control (PQC). To harness the toxicity of misfolded and damaged disease proteins, such proteins are either refolded, degraded by temporal PQC, or sequestered by spatial PQC into specific, organelle-associated, compartments within the cell. Here, we discuss the impact of vesicle trafficking pathways in general, and syntaxin 5 in particular, as key players in spatial PQC directing misfolded proteins to the surface of vacuole and mitochondria, which facilitates their clearance and detoxification. Since boosting vesicle trafficking genetically can positively impact on spatial PQC and make cells less sensitive to misfolded disease proteins, we speculate that regulators of such trafficking might serve as therapeutic targets for age-related neurological disorders.
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| 17. |
- Ahmadpour, Doryaneh, 1973, et al.
(författare)
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Syntaxin 5-dependent phosphorylation of the small heat shock protein Hsp42 and its role in protein quality control
- 2023
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Ingår i: Febs Journal. - 1742-464X. ; 290:19, s. 4744-4761
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Tidskriftsartikel (refereegranskat)abstract
- The small heat shock protein Hsp42 and the t-SNARE protein Sed5 have central roles in the sequestration of misfolded proteins into insoluble protein deposits in the yeast Saccharomyces cerevisiae. However, whether these proteins/processes interact in protein quality control (PQC) is not known. Here, we show that Sed5 and anterograde trafficking modulate phosphorylation of Hsp42 partially via the MAPK kinase Hog1. Such phosphorylation, specifically at residue S215, abrogated the co-localization of Hsp42 with the Hsp104 disaggregase, aggregate clearance, chaperone activity, and sequestration of aggregates to IPOD and mitochondria. Furthermore, we found that Hsp42 is hyperphosphorylated in old cells leading to a drastic failure in disaggregation. Old cells also displayed a retarded anterograde trafficking, which, together with slow aggregate clearance and hyperphosphorylation of Hsp42, could be counteracted by Sed5 overproduction. We hypothesize that the breakdown of proper PQC during yeast aging may, in part, be due to a retarded anterograde trafficking leading to hyperphosphorylation of Hsp42.
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| 18. |
- Amcoff Nyström, Christina, 1957-, et al.
(författare)
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Boundless collaboration : Distributed concurrent design in an inter-regional collaboration between emergency authorities
- 2014
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Ingår i: Proceedings of the DESIGN 2014 13th International Design Conference. - : The Design Society. ; , s. 1621-1630
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Konferensbidrag (refereegranskat)abstract
- The aim of the article is to evaluate how Distributed Concurrent Design works during collaboration in a distributed system development project. We studied collaboration between emergency authorities in Sweden and Norway developing a demonstrator for emergency training. Evaluation criteria were people, processes, and tools. We have used a multi-method approach with the evaluation criterion as a lens. Findings has so far shown that distributed concurrent design works as a method in system development projects but much effort must be put on planning, management and training in available tools.
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| 19. |
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| 20. |
- Andersson, Rebecca, et al.
(författare)
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Differential role of cytosolic Hsp70s in longevity assurance and protein quality control
- 2021
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- 70 kDa heat shock proteins (Hsp70) are essential chaperones of the protein quality control network; vital for cellular fitness and longevity. The four cytosolic Hsp70's in yeast, Ssa1-4, are thought to be functionally redundant but the absence of Ssa1 and Ssa2 causes a severe reduction in cellular reproduction and accelerates replicative aging. In our efforts to identify which Hsp70 activities are most important for longevity assurance, we systematically investigated the capacity of Ssa4 to carry out the different activities performed by Ssa1/2 by overproducing Ssa4 in cells lacking these Hsp70 chaperones. We found that Ssa4, when overproduced in cells lacking Ssa1/2, rescued growth, mitigated aggregate formation, restored spatial deposition of aggregates into protein inclusions, and promoted protein degradation. In contrast, Ssa4 overproduction in the Hsp70 deficient cells failed to restore the recruitment of the disaggregase Hsp104 to misfolded/aggregated proteins, to fully restore clearance of protein aggregates, and to bring back the formation of the nucleolus-associated aggregation compartment. Exchanging the nucleotide-binding domain of Ssa4 with that of Ssa1 suppressed this 'defect' of Ssa4. Interestingly, Ssa4 overproduction extended the short lifespan of ssa1 Delta ssa2 Delta mutant cells to a lifespan comparable to, or even longer than, wild type cells, demonstrating that Hsp104-dependent aggregate clearance is not a prerequisite for longevity assurance in yeast. Author summary All organisms have proteins that network together to stabilize and protect the cell throughout its lifetime. One of these types of proteins are the Hsp70s (heat shock protein 70). Hsp70 proteins take part in folding other proteins to their functional form, untangling proteins from aggregates, organize aggregates inside the cell and ensure that damaged proteins are destroyed. In this study, we investigated three closely related Hsp70 proteins in yeast; Ssa1, 2 and 4, in an effort to describe the functional difference of Ssa4 compared to Ssa1 and 2 and to answer the question: What types of cellular stress protection are necessary to reach a normal lifespan? We show that Ssa4 can perform many of the same tasks as Ssa1 and 2, but Ssa4 doesn't interact in the same manner as Ssa1 and 2 with other types of proteins. This leads to a delay in removing protein aggregates created after heat stress. Ssa4 also cannot ensure that misfolded proteins aggregate correctly inside the nucleus of the cell. However, this turns out not to be necessary for yeast cells to achieve a full lifespan, which shows us that as long as cells can prevent aggregates from forming in the first place, they can reach a full lifespan.
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| 21. |
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| 22. |
- Andersson, Stefanie, 1989, et al.
(författare)
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Genome-wide imaging screen uncovers molecular determinants of arsenite-induced protein aggregation and toxicity
- 2021
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Ingår i: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 134:11
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Tidskriftsartikel (refereegranskat)abstract
- The toxic metalloid arsenic causes widespread misfolding and aggregation of cellular proteins. How these protein aggregates are formed in vivo, the mechanisms by which they affect cells and how cells prevent their accumulation is not fully understood. To find components involved in these processes, we performed a genome-wide imaging screen and identified Saccharomyces cerevisiae deletion mutants with either enhanced or reduced protein aggregation levels during arsenite exposure. We show that many of the identified factors are crucial to safeguard protein homeostasis (proteostasis) and to protect cells against arsenite toxicity. The hits were enriched for various functions including protein biosynthesis and transcription, and dedicated follow-up experiments highlight the importance of accurate transcriptional and translational control for mitigating protein aggregation and toxicity during arsenite stress. Some of the hits are associated with pathological conditions, suggesting that arsenite-induced protein aggregation may affect disease processes. The broad network of cellular systems that impinge on proteostasis during arsenic stress identified in this current study provides a valuable resource and a framework for further elucidation of the mechanistic details of metalloid toxicity and pathogenesis. This article has an associated First Person interview with the first authors of the paper.
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| 23. |
- Andersson, Veronica, 1979, et al.
(författare)
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Enhancing protein disaggregation restores proteasome activity in aged cells
- 2013
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Ingår i: Aging-Us. - 1945-4589. ; 5:11, s. 802-812
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Tidskriftsartikel (refereegranskat)abstract
- The activity of the ubiquitin-proteasome system, UPS, declines during aging in several multicellular organisms. The reason behind this decline remains elusive. Here, using yeast as a model system, we show that while the level and potential capacity of the 26S proteasome is maintained in replicatively aged cells, the UPS is not functioning properly in vivo. As a consequence cytosolic UPS substrates, such as Delta ssCPY* are stabilized, accumulate, and form inclusions. By integrating a pGPD-HSP104 recombinant gene into the genome, we were able to constitutively elevate protein disaggregase activity, which diminished the accumulation of protein inclusions during aging. Remarkably, this elevated disaggregation restored degradation of a 26S proteasome substrate in aged cells without elevating proteasome levels, demonstrating that age-associated aggregation obstructs UPS function. The data supports the existence of a negative feedback loop that accelerates aging by exacerbating proteostatic decline once misfolded and aggregation-prone proteins reach a critical level.
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| 24. |
- Arvidsson, Niklas, et al.
(författare)
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Cirkulära möbelflöden : Hur nya affärsmodeller kan bidra till hållbar utveckling inom offentliga möbler
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Sverige har en stark möbelindustri och en stolt tradition av att tillverka tidlösa och högkvalitativa möbler, ofta av naturmaterial. 2016 producerade Sverige möbler för 22,8 miljarder SEK, varav kontorsmöbler stod för nästan en fjärdedel1. Det saknas idag statistik över vad som händer med dessa möbler när de inte längre används, men det står klart att många av dem slängs i förtid när verksamheter flyttar eller när deras behov ändras. Samtidigt syns en tydlig utveckling mot att kunder mer och mer efterfrågar återbrukade eller renoverade möbler som en del i sitt hållbarhetsarbete. Denna utveckling var startpunkten för projektet ”Affärsmodell-innovation för cirkulära möbelflöden”. Affärsmodellinnovation för cirkulära möbelflöden är ett Vinnovafinansierat projekt som under åren 2015-2017 arbetat med att utveckla och testa koncept för cirkulära affärsmodeller för i första hand offentliga möbler. I projektet har tjugo aktörer från hela värdekedjan, från underleverantörer, möbelproducenter, återförsäljare och användare till forskare och branschorgan, samarbetat kring affärsutveckling, kundincitament, produktdesign, logistik, hållbarhets- och certifieringsfrågor. Den här skriften belyser hur nya affärsmodeller för mer cirkulära möbelflöden kan bidra till en mer hållbar utveckling och ger smakprov på slutsatser från projektet. Skriften riktar sig framför allt till producenter och återförsäljare av möbler för offentliga miljöer, men även kunder och inköpare tror vi kan ha stor nytta av skriften. Vi hoppas att den även kan fungera som inspiration för andra industrier och branscher som funderar på en övergång till mer cirkulära affärsekosystem.
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| 25. |
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| 26. |
- Augestad, Ingrid Lovise, et al.
(författare)
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Normalisation of glucose metabolism by exendin-4 in the chronic phase after stroke promotes functional recovery in male diabetic mice
- 2022
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Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 179:4, s. 677-694
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: Glucagon-like peptide-1 (GLP-1) receptor activation decreases stroke risk in people with Type 2 diabetes (T2D), while animal studies have shown the efficacy of this strategy to counteract stroke-induced acute brain damage. However, whether GLP-1 receptor activation also improves recovery in the chronic phase after stroke is unknown. We investigated whether post-acute, chronic administration of the GLP-1 receptor agonist, exendin-4, improves post-stroke recovery and examined possible underlying mechanisms in T2D and non-T2D mice. Experimental Approach: We induced stroke via transient middle cerebral artery occlusion (tMCAO) in T2D/obese mice (8 months of high-fat diet) and age-matched controls. Exendin-4 was administered for 8 weeks from Day 3 post-tMCAO. We assessed functional recovery by weekly upper-limb grip strength tests. Insulin sensitivity and glycaemia were evaluated at 4 and 8 weeks post-tMCAO. Neuronal survival, stroke-induced neurogenesis, neuroinflammation, atrophy of GABAergic parvalbumin+ interneurons, post-stroke vascular remodelling and fibrotic scar formation were investigated by immunohistochemistry. Key Results: Exendin-4 normalised T2D-induced impairment of forepaw grip strength recovery in correlation with normalised glycaemia and insulin sensitivity. Moreover, exendin-4 counteracted T2D-induced atrophy of parvalbumin+ interneurons and decreased microglia activation. Finally, exendin-4 normalised density and pericyte coverage of micro-vessels and restored fibrotic scar formation in T2D mice. In non-T2D mice, the exendin-4-mediated recovery was minor. Conclusion and Implications: Chronic GLP-1 receptor activation mediates post-stroke functional recovery in T2D mice by normalising glucose metabolism and improving neuroplasticity and vascular remodelling in the recovery phase. The results warrant clinical trial of GLP-1 receptor agonists for rehabilitation after stroke in T2D.
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| 27. |
- Axelsson, Ann-Sofie, 1967, et al.
(författare)
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Taking a New Direction: Behavioral Interventions in Higher Education supported by Ajzen’s Theory of Planned Behavior
- 2010
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Ingår i: Engineering Education in Sustainable Development (EESD10), Gothenburg, Sweden, September 19-22, 2010.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- According to Ajzen [1], intentions to perform behaviors of various kinds can be predicted on the basis of attitudes towards the behavior, subjective norms, and perceived behavioral control. In the light of this theory a several weeks long exercise within six higher education courses was conducted, in order to support the students to take a new direction in their every day lives in terms of carrying out sustainable and self-imposed actions such as decreasing the use of energy in the household and eating lower on the food chain. An online questionnaire was distributed in order to find out how effective this exercise was, what the key operational mechanisms in the exercise were, and if this exercise made an impact on other areas than the one selected for this course. An analysis showed that a majority of the students perceived the exercise inspiring and motivating, supporting change of behavior in the intended, new direction. There were, however, a number of suggestions for improvement, to be seriously considered for future implementation. For example, there seems to be a need for clarifying the relevance of the task for future engineering work life. The two key operational mechanisms identified were the individual’s own attitude towards the specific behaviour and the perception that the task was within their control. A further analysis also showed that half of the students still carried out the sustainable actions after 3 months to up to 2 years and that a considerable part of them had changed their behavior within other areas. This study shows that this type of behavioral change, within a course curriculum, is very effective, and that formative research, with Ajzen's theoretical framework as a foundation, could be a starting point for this to happen.
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| 28. |
- Babazadeh, Roja, et al.
(författare)
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Syntaxin 5 Is Required for the Formation and Clearance of Protein Inclusions during Proteostatic Stress
- 2019
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 28:8
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Tidskriftsartikel (refereegranskat)abstract
- Spatial sorting to discrete quality control sites in the cell is a process harnessing the toxicity of aberrant proteins. We show that the yeast t-snare phosphoprotein syntaxin5 (Sed5) acts as a key factor in mitigating proteotoxicity and the spatial deposition and clearance of IPOD (insoluble protein deposit) inclusions associates with the disaggregase Hsp104. Sed5 phosphorylation promotes dynamic movement of COPII-associated Hsp104 and boosts disaggregation by favoring anterograde ER-to-Golgi trafficking. Hsp104-associated aggregates co-localize with Sed5 as well as components of the ER, trans Golgi network, and endocytic vesicles, transiently during proteostatic stress, explaining mechanistically how misfolded and aggregated proteins formed at the vicinity of the ER can hitchhike toward vacuolar IPOD sites. Many inclusions become associated with mitochondria in a HOPS/vCLAMP-dependent manner and co-localize with Vps39 (HOPS/vCLAMP) and Vps13, which are proteins providing contacts between vacuole and mitochondria. Both Vps39 and Vps13 are required also for efficient Sed5-dependent clearance of aggregates.
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| 29. |
- Babazadeh, Roja, et al.
(författare)
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The yeast guanine nucleotide exchange factor Sec7 is a bottleneck in spatial protein quality control and detoxifies neurological disease proteins
- 2023
-
Ingår i: Scientific Reports. - 2045-2322. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- ER-to-Golgi trafficking partakes in the sorting of misfolded cytoplasmic proteins to reduce their cytological toxicity. We show here that yeast Sec7, a protein involved in proliferation of the Golgi, is part of this pathway and participates in an Hsp70-dependent formation of insoluble protein deposits (IPOD). Sec7 associates with the disaggregase Hsp104 during a mild heat shock and increases the rate of Hsp104 diffusion in an Hsp70-dependent manner when overproduced. Sec7 overproduction increased formation of IPODs from smaller aggregates and mitigated the toxicity of Huntingtin exon-1 upon heat stress while Sec7 depletion increased sensitivity to a?42 of the Alzheimer's disease and a-synuclein of the Parkinson's disease, suggesting a role of Sec7 in mitigating proteotoxicity.
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| 30. |
- Baldeh, Tejan, et al.
(författare)
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Development and use of health outcome descriptors : a guideline development case study
- 2020
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Ingår i: Health and Quality of Life Outcomes. - : BioMed Central. - 1477-7525. ; 18:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: During healthcare guideline development, panel members often have implicit, different definitions of health outcomes that can lead to misunderstandings about how important these outcomes are and how to balance benefits and harms. McMaster GRADE Centre researchers developed ‘health outcome descriptors’ for standardizing descriptions of health outcomes and overcoming these problems to support the European Commission Initiative on Breast Cancer (ECIBC) Guideline Development Group (GDG). We aimed to determine which aspects of the development, content, and use of health outcome descriptors were valuable to guideline developers.Methods: We developed 24 health outcome descriptors related to breast cancer screening and diagnosis for the European Commission Breast Guideline Development Group (GDG). Eighteen GDG members provided feedback in written format or in interviews. We then evaluated the process and conducted two health utility rating surveys.Results: Feedback from GDG members revealed that health outcome descriptors are probably useful for developing recommendations and improving transparency of guideline methods. Time commitment, methodology training, and need for multidisciplinary expertise throughout development were considered important determinants of the process. Comparison of the two health utility surveys showed a decrease in standard deviation in the second survey across 21 (88%) of the outcomes.Conclusions: Health outcome descriptors are feasible and should be developed prior to the outcome prioritization step in the guideline development process. Guideline developers should involve a subgroup of multidisciplinary experts in all stages of development and ensure all guideline panel members are trained in guideline methodology that includes understanding the importance of defining and understanding the outcomes of interest.
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| 31. |
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| 32. |
- Beck-Friis, Thomas, et al.
(författare)
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Comparison of SARS-CoV-2 spike RNA sequences in feces and nasopharynx indicates intestinal replication
- 2022
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Ingår i: Gut Pathogens. - : Springer Science and Business Media LLC. - 1757-4749. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Little is known of possible selection and replication of SARS-CoV-2 in the intestines and if viral load in feces is associated with severity of disease. Therefore, sequence variations of the spike region in strains collected from feces and nasopharynx (NPH) from the same patients were compared. It was also investigated whether viral load in feces related to severity of COVID-19 in hospitalized patients. Results SARS-CoV-2 RNA was found in 88 (79%) fecal samples from 112 patients. The complete spike region could be sequenced in 15 fecal and 14 NPH samples. Fourteen Alpha-variants and one Beta-variant of SARS-CoV-2 were identified. The majority of the viral genetic variants (viral populations) in two fecal samples, but none in NPH, had a reversion of the H69/V70 amino acid deletion normally seen in the Alpha variants. Nine fecal samples contained up to nine minority variants, each which may constitute a separate viral population. Five NPH samples had one genetic variant each, and one NPH sample contained nine minority populations of SARS-CoV-2 spike genes. Conclusions The higher genomic diversity of SARS-CoV-2 in feces compared to NPH, and the reversion of the H69/V70 deletion in Alpha variants from feces indicate a selection of viral strains and replication of SARS-CoV-2 in the gastrointestinal tract.
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| 33. |
- Birkeland, Kare I., et al.
(författare)
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Cardiovascular mortality and morbidity in patients with type 2 diabetes following initiation of sodium-glucose co-transporter-2 inhibitors versus other glucose-lowering drugs (CVD-REAL Nordic) : A Multinational Observational Analysis
- 2017
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Ingår i: The Lancet Diabetes and Endocrinology. - New York : Elsevier. - 2213-8587 .- 2213-8595. ; 5:9, s. 709-717
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Tidskriftsartikel (refereegranskat)abstract
- Background In patients with type 2 diabetes and a high cardiovascular risk profile, the sodium-glucose co-transporter-2 (SGLT2) inhibitors empagliflozin and canagliflozin have been shown to lower cardiovascular morbidity and mortality. Using real-world data from clinical practice, we aimed to compare cardiovascular mortality and morbidity in new users of SGLT2 inhibitors versus new users of other glucose-lowering drugs, in a population with a broad cardiovascular risk profile. Methods CVD-REAL Nordic was an observational analysis of individual patient-level data from the Prescribed Drug Registers, Cause of Death Registers, and National Patient Registers in Denmark, Norway, and Sweden. All patients who filled a prescription for glucose-lowering drugs between 2012 and 2015 were included and followed up until Dec 31, 2015. Patients were divided into new users of SGLT2 inhibitors and new users of other glucose-lowering drugs. Each SGLT2 inhibitor user was matched with three users of other glucose-lowering drugs by use of propensity scores. Hazard ratios (HRs) were estimated by country (Cox survival model) and weighted averages were calculated. Cardiovascular outcomes investigated were cardiovascular mortality, major adverse cardiovascular events (cardiovascular mortality, myocardial infarction, and ischaemic or haemorrhagic stroke), hospital events for heart failure (inpatient or outpatient visit with a primary diagnosis of heart failure), non-fatal myocardial infarction, non-fatal stroke, and atrial fibrillation. We also assessed incidence of severe hypoglycaemia. Findings Matched SGLT2 inhibitor (n=22 830) and other glucose-lowering drug (n=68 490) groups were well balanced at baseline, with a mean follow-up of 0.9 (SD 4.1) years (80 669 patient-years) and mean age of 61 (12.0) years; 40% (36 362 of 91 320) were women and prevalence of cardiovascular disease was 25% (22 686 of 91 320). 94% of the total SGLT2 inhibitor exposure time was for use of dapagliflozin, with 5% for empagliflozin, and 1% for canagliflozin. Compared with other glucose-lowering drugs, use of SGLT2 inhibitors was associated with decreased risk of cardiovascular mortality (HR 0.53 [95% CI 0.40-0.71]), major adverse cardiovascular events (0.78 [0.69-0.87]), and hospital events for heart failure (0.70 [0.61-0.81]; p<0.0001 for all). We did not identify significant differences between use of SGLT2 inhibitors and use of other glucose-lowering drugs for non-fatal myocardial infarction, non-fatal stroke, or atrial fibrillation. Compared with other glucose-lowering drugs, use of SGLT2 inhibitors was associated with a decreased risk of severe hypoglycaemia (HR 0.76 [0.65-0.90]; p=0.001). For cardiovascular mortality, the differences were similar for the 25% of individuals with cardiovascular disease at baseline and those without (HR 0.60 [0.42-0.85] vs 0.55 [0.34-0.90]), while for major adverse cardiovascular events the HR in the group with cardiovascular disease at baseline was 0.70 (0.59-0.83) versus 0.90 (0.76-1.07) in the group without. Interpretation In a population of patients with type 2 diabetes and a broad cardiovascular risk profile, SGLT2 inhibitor use was associated with reduced cardiovascular disease and cardiovascular mortality compared with use of other glucose-lowering drugs-a finding consistent with the results of clinical trials in patients at high cardiovascular risk.
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| 34. |
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| 35. |
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| 36. |
- Boyer, Robert, et al.
(författare)
-
Three-dimensional product circularity
- 2021
-
Ingår i: Journal of Industrial Ecology. - : John Wiley & Sons, Ltd. - 1088-1980 .- 1530-9290. ; 25:4, s. 824-
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Understanding product circularity as ?three-dimensional? could anchor the Circular Economy to common principles while affording its followers flexibility about how to measure it in their specific sectors and disciplines and within their organization's means. Inspired by a heuristic developed for the urban planning profession to cope with the inherent conflicts of Sustainable Development, this article argues that measuring product-level circularity should consider ways to achieve (1) high material recirculation, (2) high utilization, and (3) high endurance in products and service offerings. Achieving all three dimensions ensures that material flowing through the economy is recovered from prior use phases, that it is used intensely, and that it retains its value in spite of exogenous changes. The article argues further that these three dimensions ought to be measured and reported separately rather than as a composite metric and that certain applications will have opportunities to improve circularity through certain dimensions better than others. The article also explains how researchers at RISE (Research Institutes of Sweden AB) are working with industry and government partners to measure the three dimensions and how diverse actors interested in the Circular Economy can use the three dimensions to take the first steps in their transition to circularity.
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| 37. |
- Brenner, Thomas, et al.
(författare)
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New editors-in-chief and editorial board
- 2023
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Ingår i: Jahrbuch für Regional Wissenschaft. - : Springer Nature. - 0173-7600 .- 1613-9836. ; 43:3, s. 363-365
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 38. |
- Brunklaus, Birgit, 1970-, et al.
(författare)
-
Den cirkulära bilen (förstudie)
- 2023
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Syftet med förstudien Den cirkulära bilen var att börja bygga konkreta visioner som möjliggör att Sverige har en cirkulärt anpassad bilflotta med fossilfria och klimatneutrala transporter år 2045 och att bygga en solid bas för ett steg 2-projekt, som i sin tur kommer att ge stöd och kapacitet för aktörer att accelerera den cirkulära bilvärdekedjan. Projektet har samlat 13 parter från hela värdekedjan och gemensamt lagt grunden till vidare arbete i ett fortsättningsprojekt – en ansökan som genererat intresse från ett stort antal parter både befintliga och nytillkommande. Inom studien har startmöten och workshops genomförts där parter samlats digitalt och frågeställningar sonderats. Intervjuer har genomförts med parter där möjligheter och utmaningar med omställningen diskuterats. Studiebesök har genomförts där kunskapsdelning skett och samverkan möjliggjorts. Fysisk workshop har genomförts med samtliga parter. Här tittade man gemensamt på trender och möjliga framtidsscenarios genom hela systemet. Detta gav en bra grund för det vidare arbetet med steg 2. Förstudien har genererat stort intresse från aktörer i hela värdekedjan, skapat nya kontakter och möjligheter till samverkan och blivit uppstarten på en gemensam kunskapsresa för verklig förändring. Studien har initierat arbete brett i värdekedjan kopplat till gemensamma frågeställningar samt framtidsspaningar, vilket möjliggör gemensamt arbete för bred omställning och tydliggjort behovet av åtgärder som förflyttar hela systemet. Detta ses som en god grund för ett steg 2 projekt med förutsättningar för att förverkliga den cirkulära bilvärdekedjan.
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| 39. |
- Brändström, Helena, et al.
(författare)
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A single nucleotide polymorphism in the promoter region of the osteoprotegerin gene is related to intima-media thickness of the carotid artery in hypertensive patients : The Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA)
- 2004
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Ingår i: Blood Pressure. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 13:3, s. 152-157
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Tidskriftsartikel (refereegranskat)abstract
- Osteoprotegerin (OPG) is a secreted member of the tumor necrosis factor receptor family, and in previous studies has been shown to regulate osteoclast activity and differentiation. Ablation of the OPG gene in mice results in calcification of the aorta and renal arteries. We have previously reported an association between a single nucleotide polymorphism in the promoter region of OPG and vascular morphology and function in healthy humans. The objective with this study was to confirm our previous results in a larger population, and in addition, to study subjects with hypertension. The OPG genotype was determined by restriction fragment length and the intima-media thickness (IMT) of the common carotid artery was measured by ultrasound in 100 patients with hypertension and left ventricular hypertrophy, and 75 healthy normotensive control subjects. In the hypertensive group subjects with the CC genotype (n=24) showed a significantly increased IMT compared to those with the TC (n=52, p=0.007) and TT (n=24, p=0.009) genotype, in the hypertensive group only (mean +/- SD for TT=0.88 +/- 0.21 mm, TC=0.90 +/- 0.16 mm, CC=1.05 +/- 0.31 mm). The allele distribution did not differ between hypertensive and control individuals. The present study confirms our previous finding and shows that polymorphism in the promoter region of OPG is associated with vascular morphology in hypertensive subjects.
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| 40. |
- Bylund, Johan, 1975, et al.
(författare)
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Proinflammatory activity of a cecropin-like antibacterial peptide from Helicobacter pylori
- 2001
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Ingår i: Antimicrob Agents Chemother. ; 45:6, s. 1700-4
-
Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori, the bacterial pathogen associated with gastritis and peptic ulcers, is highly successful in establishing infection in the human gastric mucosa, a process typically associated with massive infiltration of inflammatory cells. Colonization of the mucosa is suggested to be facilitated by H. pylori-produced cecropin-like peptides with antibacterial properties, giving the microbe a competitive advantage over other bacteria. We show that a cecropin-like antibacterial peptide from H. pylori, Hp(2-20), not only has a potent bactericidal effect but also induces proinflammatory activities in human neutrophils, e.g., upregulation of integrins (Mac-1), induction of chemotaxis, and activation of the oxygen radical producing NADPH-oxidase. Furthermore, we show that these effects are mediated through binding of Hp(2-20) to the promiscuous, G-protein-linked lipoxin A(4) receptor-formyl peptide-like receptor 1.
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| 41. |
- Byskov, Camilla S., et al.
(författare)
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Treatment plan comparison of proton vs photon radiotherapy for lower-grade gliomas
- 2021
-
Ingår i: Physics and Imaging in Radiation Oncology. - : Elsevier. - 2405-6316. ; 20, s. 98-104
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Patients with lower-grade gliomas are long-term survivors after radiotherapy and may benefit from the reduced dose to normal tissue achievable with proton therapy. Here, we aimed to quantify differences in dose to the uninvolved brain and contralateral hippocampus and compare the risk of radiation-induced secondary cancer for photon and proton plans for lower-grade glioma patients. Materials and methods: Twenty-three patients were included in this in-silico planning comparative study and had photon and proton plans calculated (50.4 Gy(RBE = 1.1), 28 Fx) applying similar dose constraints to the target and organs at risk. Automatically calculated photon plans were generated with a 3 mm margin from clinical target volume (CTV) to planning target volume. Manual proton plans were generated using robust optimisation on the CTV. Dose metrics of organs at risk were compared using population mean dose-volume histograms and Wilcoxon signed-rank test. Secondary cancer risk per 10,000 persons per year (PPY) was estimated using dose-volume data and a risk model for secondary cancer induction. Results: CTV coverage (V95%>98%) was similar for the two treatment modalities. Mean dose (D-mean) to the uninvolved brain was significantly reduced from 21.5 Gy (median, IQR 17.1-24.4 Gy) with photons compared to 10.3 Gy(RBE) (8.1-13.9 Gy(RBE)) with protons. D-mean to the contralateral hippocampus was significantly reduced from 6.5 Gy (5.4-11.7 Gy) with photons to 1.5 Gy(RBE) (0.4-6.8 Gy(RBE)) with protons. The estimated secondary cancer risk was reduced from 6.7 PPY (median, range 3.3-10.4 PPY) with photons to 3.0 PPY (1.3-7.5 PPY) with protons. Conclusion: A significant reduction in mean dose to uninvolved brain and contralateral hippocampus was found with proton planning. The estimated secondary cancer risk was reduced with proton therapy.
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| 42. |
- Caballero, Antonio, et al.
(författare)
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Absence of mitochondrial translation control proteins extends life span by activating sirtuin-dependent silencing.
- 2011
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Ingår i: Molecular cell. - : Elsevier BV. - 1097-4164 .- 1097-2765. ; 42:3, s. 390-400
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Tidskriftsartikel (refereegranskat)abstract
- Altered mitochondrial functionality can extend organism life span, but the underlying mechanisms are obscure. Here we report that inactivating SOV1, a member of the yeast mitochondrial translation control (MTC) module, causes a robust Sir2-dependent extension of replicative life span in the absence of respiration and without affecting oxidative damage. We found that SOV1 interacts genetically with the cAMP-PKA pathway and the chromatin remodeling apparatus. Consistently, Sov1p-deficient cells displayed reduced cAMP-PKA signaling and an elevated, Sir2p-dependent, genomic silencing. Both increased silencing and life span extension in sov1Δ cells require the PKA/Msn2/4p target Pnc1p, which scavenges nicotinamide, a Sir2p inhibitor. Inactivating other members of the MTC module also resulted in Sir2p-dependent life span extension. The data demonstrate that the nuclear silencing apparatus senses and responds to the absence of MTC proteins and that this response converges with a pathway for life span extension elicited by reducing TOR signaling.
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| 43. |
- Carlsson, Richard, et al.
(författare)
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Core Erlang 1.0 language specification
- 2000
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- We describe a core language for the concurrent functional language Erlang, aptly named “Core Erlang”, presenting its grammar and informal static and dynamic semantics relative to Erlang. We also discuss built-in functions and other open issues, and sketch a syntax tree representation.
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| 44. |
- Carlsten, Jonas O P, et al.
(författare)
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Mediator Promotes CENP-A Incorporation at Fission Yeast Centromeres
- 2012
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Ingår i: Molecular and Cellular Biology. - : Informa UK Limited. - 0270-7306 .- 1098-5549. ; 32:19, s. 4035-4043
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Tidskriftsartikel (refereegranskat)abstract
- At Schizosaccharomyces pombe centromeres, heterochromatin formation is required for de novo incorporation of the histone H3 variant CENP-A(Cnp1), which in turn directs kinetochore assembly and ultimately chromosome segregation during mitosis. Noncoding RNAs (ncRNAs) transcribed by RNA polymerase II (Pol II) directs heterochromatin formation through not only the RNA interference (RNAi) machinery but also RNAi-independent RNA processing factors. Control of centromeric ncRNA transcription is therefore a key factor for proper centromere function. We here demonstrate that Mediator directs ncRNA transcription and regulates centromeric heterochromatin formation in fission yeast. Mediator colocalizes with Pol II at centromeres, and loss of the Mediator subunit Med20 causes a dramatic increase in pericentromeric transcription and desilencing of the core centromere. As a consequence, heterochromatin formation is impaired via both the RNAi-dependent and -independent pathways, resulting in loss of CENP-A(Cnp1) from the core centromere, a defect in kinetochore function, and a severe chromosome segregation defect. Interestingly, the increased centromeric transcription observed in med20 Delta cells appears to directly block CENP-A(Cnp1) incorporation since inhibition of Pol II transcription can suppress the observed phenotypes. Our data thus identify Mediator as a crucial regulator of ncRNA transcription at fission yeast centromeres and add another crucial layer of regulation to centromere function.
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| 45. |
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| 46. |
- Carmona-Gutierrez, D., et al.
(författare)
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Guidelines and recommendations on yeast cell death nomenclature
- 2018
-
Ingår i: Microbial Cell. - : Shared Science Publishers OG. - 2311-2638. ; 5:1, s. 4-31
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Forskningsöversikt (refereegranskat)abstract
- Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cellular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing. Here, we propose unified criteria for the definition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria. Specifically, we provide consensus guidelines on the differential definition of terms including apoptosis, regulated necrosis, and autophagic cell death, as we refer to additional cell death routines that are relevant for the biology of (at least some species of) yeast. As this area of investigation advances rapidly, changes and extensions to this set of recommendations will be implemented in the years to come. Nonetheless, we strongly encourage the authors, reviewers and editors of scientific articles to adopt these collective standards in order to establish an accurate framework for yeast cell death research and, ultimately, to accelerate the progress of this vibrant field of research.
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| 47. |
- Casiraghi, I, et al.
(författare)
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First principle-based multi-channel integrated modelling in support of the design of the Divertor Tokamak Test facility
- 2021
-
Ingår i: Nuclear Fusion. - : IOP Publishing Ltd. - 0029-5515 .- 1741-4326. ; 61:11
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Tidskriftsartikel (refereegranskat)abstract
- An intensive integrated modelling work of the main scenarios of the new Divertor Tokamak Test (DTT) facility with a single null divertor configuration has been performed using first principle quasi-linear transport models, in support of the design of the device and of the definition of its scientific work programme. First results of this integrated modelling work on DTT (R (0) = 2.14 m, a = 0.65 m) are presented here along with outcome of the gyrokinetic simulations used to validate the reduced models in the DTT range of parameters. As a result of this work, the heating mix has been defined, the size of device has been increased to R (0) = 2.19 m and a = 0.70 m, the use of pellets for fuelling has been recommended and reference profiles for diagnostic design, estimates of neutron yields and fast particle losses have been made available.
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| 48. |
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| 49. |
- Chawla, Srishti, 1986, et al.
(författare)
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Calcineurin stimulation by Cnb1p overproduction mitigates protein aggregation and α-synuclein toxicity in a yeast model of synucleinopathy
- 2023
-
Ingår i: Cell Communication and Signaling. - 1478-811X. ; 21:1
-
Tidskriftsartikel (refereegranskat)abstract
- The calcium-responsive phosphatase, calcineurin, senses changes in Ca2+ concentrations in a calmodulin-dependent manner. Here we report that under non-stress conditions, inactivation of calcineurin signaling or deleting the calcineurin-dependent transcription factor CRZ1 triggered the formation of chaperone Hsp100p (Hsp104p)-associated protein aggregates in Saccharomyces cerevisiae. Furthermore, calcineurin inactivation aggravated α-Synuclein-related cytotoxicity. Conversely, elevated production of the calcineurin activator, Cnb1p, suppressed protein aggregation and cytotoxicity associated with the familial Parkinson’s disease-related mutant α-Synuclein A53T in a partly CRZ1-dependent manner. Activation of calcineurin boosted normal localization of both wild type and mutant α-synuclein to the plasma membrane, an intervention previously shown to mitigate α-synuclein toxicity in Parkinson’s disease models. The findings demonstrate that calcineurin signaling, and Ca2+ influx to the vacuole, limit protein quality control in non-stressed cells and may have implications for elucidating to which extent aberrant calcineurin signaling contributes to the progression of Parkinson’s disease(s) and other synucleinopathies. [MediaObject not available: see fulltext.].
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| 50. |
- Chen, Rong, et al.
(författare)
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An archetype-based testing framework
- 2008
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Ingår i: eHealth Beyond the Horizon. - Amsterdam, Netherlands : IOS Press. - 9781586038649 ; 136, s. 401-6
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Konferensbidrag (refereegranskat)abstract
- With the introduction of EHR two-level modelling and archetype methodologies pioneered by openEHR and standardized by CEN/ISO, we are one step closer to semantic interoperability and future-proof adaptive healthcare information systems. Along with the opportunities, there are also challenges. Archetypes provide the full semantics of EHR data explicitly to surrounding systems in a platform-independent way, yet it is up to the receiving system to interpret the semantics and process the data accordingly. In this paper we propose a design of an archetype-based platform-independent testing framework for validating implementations of the openEHR archetype formalism as a means of improving quality and interoperability of EHRs.
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