| 1. |
- Abildgaard, Amanda B., et al.
(author)
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HSP70-binding motifs function as protein quality control degrons
- 2023
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In: Cellular and Molecular Life Sciences (CMLS). - : Springer Science and Business Media LLC. - 1420-682X .- 1420-9071. ; 80:1
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Journal article (peer-reviewed)abstract
- Protein quality control (PQC) degrons are short protein segments that target misfolded proteins for proteasomal degradation, and thus protect cells against the accumulation of potentially toxic non-native proteins. Studies have shown that PQC degrons are hydrophobic and rarely contain negatively charged residues, features which are shared with chaperone-binding regions. Here we explore the notion that chaperone-binding regions may function as PQC degrons. When directly tested, we found that a canonical Hsp70-binding motif (the APPY peptide) functioned as a dose-dependent PQC degron both in yeast and in human cells. In yeast, Hsp70, Hsp110, Fes1, and the E3 Ubr1 target the APPY degron. Screening revealed that the sequence space within the chaperone-binding region of APPY that is compatible with degron function is vast. We find that the number of exposed Hsp70-binding sites in the yeast proteome correlates with a reduced protein abundance and half-life. Our results suggest that when protein folding fails, chaperone-binding sites may operate as PQC degrons, and that the sequence properties leading to PQC-linked degradation therefore overlap with those of chaperone binding.
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| 2. |
- Baugh, Lee A., et al.
(author)
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Representing multiple object weights : competing priors and sensorimotor memories
- 2016
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In: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 116:4, s. 1615-1625
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Journal article (peer-reviewed)abstract
- When lifting an object, individuals scale lifting forces based on long-term priors relating external object properties (such as material and size) to object weight. When experiencing objects that are poorly predicted by priors, people rapidly form and update sensorimotor memories that can be used to predict an object's atypical size-weight relation in support of predictively scaling lift forces. With extensive experience in lifting such objects, long-term priors, assessed with weight judgments, are gradually updated. The aim of the present study was to understand the formation and updating of these memory processes. Participants lifted, over multiple days, a set of black cubes with a normal size-weight mapping and green cubes with an inverse size-weight mapping. Sensorimotor memory was assessed with lifting forces, and priors associated with the black and green cubes were assessed with the size-weight illusion (SWI). Interference was observed in terms of adaptation of the SWI, indicating that priors were not independently adjusted. Half of the participants rapidly learned to scale lift forces appropriately, whereas reduced learning was observed in the others, suggesting that individual differences may be affecting sensorimotor memory abilities. A follow-up experiment showed that lifting forces are not accurately scaled to objects when concurrently performing a visuomotor association task, suggesting that sensorimotor memory formation involves cognitive resources to instantiate the mapping between object identity and weight, potentially explaining the results of experiment 1. These results provide novel insight into the formation and updating of sensorimotor memories and provide support for the independent adjustment of sensorimotor memory and priors.
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| 6. |
- Bryhn, Andreas, et al.
(author)
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A continuous involvement of stakeholders promotes the ecosystem approach to fisheries in the 8-fjords area on the Swedish west coast
- 2017
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In: ICES Journal of Marine Science. - : Oxford University Press (OUP). - 1054-3139 .- 1095-9289. ; 74, s. 431–442-
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Journal article (peer-reviewed)abstract
- The coastal marine environment in the 8-fjords area on the Swedish west coast has been subjected to various stakeholder co-management initiatives since 1999. Stakeholders and authorities have acted by supporting and implementing gradually stricter fishing restrictions following the collapse in the 1970s of several demersal fish stocks and their apparent lack of recovery. Moreover, concerns have been raised regarding a locally sharp depletion of eelgrass meadows, in addition to an apparent increase in the number of seals and cormorants. The present 8-fjords initiative applies a cross-sector approach to environmental management and thus also addresses various types of environmental pollution. This study has compared the environmental work around the 8-fjords to 15 principles regarding the ecosystem approach to fisheries (EAF). The main strength that has been identified among the EAF principles is the continuous involvement of stakeholders. Among weaknesses in the EAF is the scarcity of suitable indicators that are necessary for appropriate monitoring, especially biomasses of functional groups as well as economic and social indicators. Many environmental problems in the fjords remain and it is possible that improved adherence to EAF principles will facilitate solving some problems and alleviating others. Moreover, the application of the EAF in practice in the 8-fjords can serve as a guiding example for co-managing other aquatic ecosystems towards ecological, economic, and social sustainability. The experiences from the 8-fjords initiative, including its extensive stakeholder involvement, may serve as a practical EAF example to be studied by researchers and managers globally.
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| 7. |
- Carlander, Anders, 1979, et al.
(author)
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Choices of savings options related to trust in banks’ competence, benevolence and stability
- 2013
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In: Journal of Financial Services Marketing. - : Springer Science and Business Media LLC. - 1363-0539 .- 1479-1846. ; 18:2, s. 121-136
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Journal article (peer-reviewed)abstract
- The study investigates whether beliefs in professional investor skill in conjunction with trust in banks and other fund managers explain choices of options for long-term savings. From questionnaire data obtained for a population-based sample (n=178) and a sample of undergraduates (n=186), two index measures were constructed, one of beliefs in the skill of professional investors and another of trust in fund managers. The trust index was aggregated for the three interrelated components: competence, benevolence and stability. Regression analyses of the likelihood of savings in an actively managed fund showed an expected effect of investor-skill beliefs that was mediated by trust in the fund manager. In addition, self-reported knowledge played a larger role than trust for choices of passively managed index funds and in particular for own investment in stocks.
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| 8. |
- Carlander, Anders, 1979, et al.
(author)
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The role of perceived quality of personal service in influencing trust and satisfaction with banks
- 2018
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In: Financial Services Review. - 1057-0810. ; 27, s. 83-98
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Journal article (peer-reviewed)abstract
- Trust is of paramount importance to banks. Previous research has shown that trust increases with repeated personal contacts. We investigate if this applies to the customer-employee relationship in banks. Data from an on-line survey of 293 customers of Swedish retail banks are used to construct indicator measures. By means of structural equation modeling we find that trust in the bank is influenced by perceived quality of personal service through employees’ perceived competence, perceived benevolence, and perceived transparency, and that satisfaction with the bank is influenced by perceived quality of personal service through perceived competence, perceived benevolence, perceived transparency, and trust.
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| 9. |
- Chen, H.Y., et al.
(author)
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Dyslipidemia, inflammation, calcification, and adiposity in aortic stenosis: a genome-wide study
- 2023
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In: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 44:21, s. 1927-1939
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Journal article (peer-reviewed)abstract
- Aims Although highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS. Methods and results A genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10−8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2–SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26–1.35; P = 2.7 × 10−51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08–1.37; P = 1.4 × 10−3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90–5.12; P = 2.1 × 10−20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17–1.23; P = 4.8 × 10−73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05–1.9; P = 1.9 × 10−12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS. Conclusion Dyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies. © The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.
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| 10. |
- Dahl, Andrew, et al.
(author)
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A multiple-phenotype imputation method for genetic studies
- 2016
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:4, s. 466-472
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Journal article (peer-reviewed)abstract
- Genetic association studies have yielded a wealth of biological discoveries. However, these studies have mostly analyzed one trait and one SNP at a time, thus failing to capture the underlying complexity of the data sets. Joint genotype-phenotype analyses of complex, high-dimensional data sets represent an important way to move beyond simple genome-wide association studies (GWAS) with great potential. The move to high-dimensional phenotypes will raise many new statistical problems. Here we address the central issue of missing phenotypes in studies with any level of relatedness between samples. We propose a multiple-phenotype mixed model and use a computationally efficient variational Bayesian algorithm to fit the model. On a variety of simulated and real data sets from a range of organisms and trait types, we show that our method outperforms existing state-of-the-art methods from the statistics and machine learning literature and can boost signals of association.
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