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- Ahmadpour, Doryaneh, 1973, et al.
(author)
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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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In: Febs Journal. - 1742-464X. ; 290:19, s. 4744-4761
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Journal article (peer-reviewed)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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- Andersson, Stefanie, 1989, et al.
(author)
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Genome-wide imaging screen uncovers molecular determinants of arsenite-induced protein aggregation and toxicity
- 2021
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In: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 134:11
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Journal article (peer-reviewed)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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- Axelsson, Ann-Sofie, 1967, et al.
(author)
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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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In: Engineering Education in Sustainable Development (EESD10), Gothenburg, Sweden, September 19-22, 2010.
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Conference paper (other academic/artistic)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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- Brunklaus, Birgit, 1970-, et al.
(author)
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Den cirkulära bilen (förstudie)
- 2023
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Reports (other academic/artistic)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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- Chawla, Srishti, 1986, et al.
(author)
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Calcineurin stimulation by Cnb1p overproduction mitigates protein aggregation and α-synuclein toxicity in a yeast model of synucleinopathy
- 2023
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In: Cell Communication and Signaling. - 1478-811X. ; 21:1
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Journal article (peer-reviewed)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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| 10. |
- Faergemann, Jan, 1948, et al.
(author)
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Pentane-1,5-diol as a percutaneous absorption enhancer
- 2005
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In: Arch Dermatol Res. - : Springer Science and Business Media LLC. ; 297:6, s. 261-5
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Journal article (peer-reviewed)abstract
- Propylene glycol (propane-1,2-diol) is the only diol widely used in dermatology. Pentane-1,5-diol is mainly used as a plasticizer in cellulose products and adhesives, in dental composites and in brake fluid compositions and as a preservative for grain. However, pentane-1,5-diol is also an effective solvent, water-binding substance, antimicrobial agent and preservative and may therefore replace several ingredients in a skin composition. The release of tri-iodothyroacetic acid (TRIAC) and percutaneous absorption of hydrocortisone and mometasone furoate with either pentane-1,5-diol or propane-1,2-diol and 2-methyl-pentane-2,4-diol (hexylene glycol), respectively, as enhancers was compared. The release of TRIAC was 21% higher when pentane-1,5-diol was used as an enhancer instead of propane-1,2-diol. The percutaneous absorption of hydrocortisone through the skin was increased 12 times with propane-1,2-diol compared to 4.4 times with pentane-1,5-diol. However, the percutaneous absorption of hydrocortisone into the skin was 50% higher with pentane-1,5-diol compared to propane-1,2-diol. There was no significant difference, between the original mometasone furoate cream, with 2-methyl-pentane-2,4-diol, and the new cream with pentane-1,5-diol in the amount of mometasone furoate that was absorbed into the skin and through the skin. However, the cosmetic properties of the new mometasone furoate cream was superior to the original mometasone furoate cream, for examples, no bad odour, more even texture, goes better into the skin and has less greasiness. Pentane-1,5-diol can be used as a technology platform, which adds a series of desirable properties to dermatological preparations and enhances product usability. This will result in improved formulations for a series of major and commonly used dermatological drugs. When used in pharmaceutical topical preparations, pentane-1,5-diol will increase the percutaneous absorption of the active substance and it is an efficient antimicrobial agent that will act as an effective preservative in topical formulations. Pentane-1,5-diol is cosmetically attractive, has low risk for skin and eye irritation compared to other diols, low toxicity risk and no bad odour.
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