| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 3. |
- Jones, Geraint H., et al.
(författare)
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The Comet Interceptor Mission
- 2024
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Ingår i: Space Science Reviews. - : Springer Nature. - 0038-6308 .- 1572-9672. ; 220:1
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Tidskriftsartikel (refereegranskat)abstract
- Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA’s F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum Δ V capability of 600 ms − 1 . Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes – B1, provided by the Japanese space agency, JAXA, and B2 – that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission’s science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule.
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| 4. |
- Sorokowska, Agnieszka, et al.
(författare)
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Affective Interpersonal Touch in Close Relationships : A Cross-Cultural Perspective
- 2021
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Ingår i: Personality and Social Psychology Bulletin. - : Sage Publications. - 0146-1672 .- 1552-7433. ; 47:12, s. 1705-1721
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Tidskriftsartikel (refereegranskat)abstract
- Interpersonal touch behavior differs across cultures, yet no study to date has systematically tested for cultural variation in affective touch, nor examined the factors that might account for this variability. Here, over 14,000 individuals from 45 countries were asked whether they embraced, stroked, kissed, or hugged their partner, friends, and youngest child during the week preceding the study. We then examined a range of hypothesized individual-level factors (sex, age, parasitic history, conservatism, religiosity, and preferred interpersonal distance) and cultural-level factors (regional temperature, parasite stress, regional conservatism, collectivism, and religiosity) in predicting these affective-touching behaviors. Our results indicate that affective touch was most prevalent in relationships with partners and children, and its diversity was relatively higher in warmer, less conservative, and religious countries, and among younger, female, and liberal people. This research allows for a broad and integrated view of the bases of cross-cultural variability in affective touch.
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| 5. |
- Sorokowski, Piotr, et al.
(författare)
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Universality of the Triangular Theory of Love : Adaptation and Psychometric Properties of the Triangular Love Scale in 25 Countries
- 2021
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Ingår i: Journal of Sex Research. - : Informa UK Limited. - 0022-4499 .- 1559-8519. ; 58:1, s. 106-115
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Tidskriftsartikel (refereegranskat)abstract
- The Triangular Theory of Love (measured with Sternberg's Triangular Love Scale - STLS) is a prominent theoretical concept in empirical research on love. To expand the culturally homogeneous body of previous psychometric research regarding the STLS, we conducted a large-scale cross-cultural study with the use of this scale. In total, we examined more than 11,000 respondents, but as a result of applied exclusion criteria, the final analyses were based on a sample of 7332 participants from 25 countries (from all inhabited continents). We tested configural invariance, metric invariance, and scalar invariance, all of which confirmed the cultural universality of the theoretical construct of love analyzed in our study. We also observed that levels of love components differ depending on relationship duration, following the dynamics suggested in the Triangular Theory of Love. Supplementary files with all our data, including results on love intensity across different countries along with STLS versions adapted in a few dozen languages, will further enable more extensive research on the Triangular Theory of Love.
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| 6. |
- Carreira, Abel Santos, et al.
(författare)
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Bloodstream Infections and Outcomes Following Allogeneic Hematopoietic Cell Transplantation : A Single-Center Study
- 2022
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Ingår i: Transplantation and Cellular Therapy. - : Elsevier. - 2666-6375 .- 2666-6367. ; 28:1, s. 50.e1-50.e8
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated the single-center incidence and risk factors for bloodstream infections (BSIs) in 651 adults who underwent allogeneic hematopoietic cell transplantation (alloHCT) between 2015 and 2019 and explored the impact of these BSIs on post-transplantation outcomes. Antibiotic prophylaxis with ciprofloxacin was given during the aplastic phase. Overall, the median patient age was 57 years, 79.7% of patients received an alternative donor graft, and 68.7% received post-transplantation cyclophosphamide (PTCy) as part of their graft-versus-host disease (GVHD) prophylaxis. Of the 651 patients, 358 (55.0%) had at least 1 episode of BSI, and the overall mortality rate secondary to this complication was 7.5% (12.6% among those diagnosed with at least 1 episode of BSI). BSI was more often diagnosed during the first 30 days (58.7%), and gram-positive bacteria were the most prevalent microorganisms isolated during the entire post-transplantation follow-up (62%). A high Disease Risk Index (hazard ratio [HR], 1.47; P < .029) and receipt of PTCy-based GVHD prophylaxis (HR, 3.33; P < .001) were identified as risk factors for BSI. Additionally, univariate analysis showed that patients diagnosed with a BSI during post-transplantation follow-up had worse overall survival (HR, 2.48; P < .001) and higher nonrelapse mortality (HR, 2.68; P < .001) than those without BSI. In conclusion, alloHCT recipients with a BSI had a higher risk of mortality compared with those who did not develop BSI. The inclusion of PTCy as part of GVHD prophylaxis was identified as an independent risk factor for BSI during early post-transplantation follow-up. Single-center analyses focused on reporting the incidence and risk factors for BSI highlight the need for active implementation of preemptive strategies to decrease BSI incidence in the alloHCT setting.
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| 7. |
- Coyle, Daisy, et al.
(författare)
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Estimating the potential impact of Australia's reformulation programme on households' sodium purchases.
- 2021
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Ingår i: BMJ Nutrition, Prevention & Health. - : BMJ Publishing Group Ltd. - 2516-5542. ; 4:1, s. 49-58
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Tidskriftsartikel (refereegranskat)abstract
- Background: On average, Australian adults consume 3500 mg sodium per day, almost twice the recommended maximum level of intake. The Australian government through the Healthy Food Partnership initiative has developed a voluntary reformulation programme with sodium targets for 27 food categories. We estimated the potential impact of this programme on household sodium purchases (mg/day per capita) and examined potential differences by income level. We also modelled and compared the effects of applying the existing UK reformulation programme targets in Australia.Methods: This study used 1 year of grocery purchase data (2018) from a nationally representative consumer panel of Australian households (Nielsen Homescan) that was linked with a packaged food and beverage database (FoodSwitch) that contains product-specific sodium information. Potential reductions in per capita sodium purchases were calculated and differences across income level were assessed by analysis of variance. All analyses were modelled to the Australian population in 2018.Results: A total of 7188 households were included in the analyses. The Healthy Food Partnership targets covered 4307/26 728 (16.1%) unique products, which represented 22.3% of all packaged foods purchased by Australian households in 2018. Under the scenario that food manufacturers complied completely with the targets, sodium purchases will be reduced by 50 mg/day per capita, equivalent to 3.5% of sodium currently purchased from packaged foods. Reductions will be greater in low-income households compared with high-income households (mean difference -7 mg/day, 95% CI -4 to -11 mg/day, p<0.001). If Australia had adopted the UK sodium targets, this would have covered 9927 unique products, resulting in a reduction in per capita sodium purchases by 110 mg/day.Conclusion: The Healthy Food Partnership reformulation programme is estimated to result in a very small reduction to sodium purchases. There are opportunities to improve the programme considerably through greater coverage and more stringent targets.
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| 8. |
- Coyle, Daisy H, et al.
(författare)
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Contribution of major food companies and their products to household dietary sodium purchases in Australia
- 2020
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Ingår i: International Journal of Behavioral Nutrition and Physical Activity. - : BioMed Central (BMC). - 1479-5868. ; 17:1, s. 2-9
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Australian federal government will soon release voluntary sodium reduction targets for 30 packaged food categories through the Healthy Food Partnership. Previous assessments of voluntary targets show variable industry engagement, and little is known about the extent that major food companies and their products contribute to dietary sodium purchases among Australian households.Methods: The aim of this cross-sectional study was to identify the relative contribution that food companies and their products made to Australian household sodium purchases in 2018, and to examine differences in sodium purchases by household income level. We used 1 year of grocery purchase data from a nationally representative consumer panel of Australian households who reported their grocery purchases (the Nielsen Homescan panel), combined with database that contains product-specific sodium content for packaged foods and beverages (FoodSwitch). The top food companies and food categories were ranked according to their contribution to household sodium purchases. Differences in per capita sodium purchases by income levels were assessed by 1-factor ANOVA. All analyses were modelled to the Australian population in 2018 using sample weights.Results: Sodium data were available from 7188 households who purchased 26,728 unique products and purchased just under 7.5 million food product units. Out of 1329 food companies, the top 10 accounted for 35% of unique products and contributed to 58% of all sodium purchased from packaged foods and beverages. The top three companies were grocery food retailers each contributing 12-15% of sodium purchases from sales of their private label products, particularly processed meat, cheese and bread. Out of the 67 food categories, the top 10 accounted for 73% of sodium purchased, particularly driven by purchases of processed meat (14%), bread (12%) and sauces (11%). Low-income Australian households purchased significantly more sodium from packaged products than high-income households per capita (452 mg/d, 95%CI: 363-540 mg/d, P < 0.001).Conclusions: A small number of food companies and food categories account for most of the dietary sodium purchased by Australian households. Prioritizing government engagement with these groups could deliver a large reduction in population sodium intake.
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| 9. |
- Coyle, Daisy H, et al.
(författare)
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Estimating the potential impact of the Australian government's reformulation targets on household sugar purchases.
- 2021
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Ingår i: International Journal of Behavioral Nutrition and Physical Activity. - : Springer Nature. - 1479-5868. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Countries around the world are putting in place sugar reformulation targets for packaged foods to reduce excess sugar consumption. The Australian government released its voluntary sugar reformulation targets for nine food categories in 2020. We estimated the potential impact of these targets on household sugar purchases and examined differences by income. For comparison, we also modelled the potential impact of the UK sugar reduction targets on per capita sugar purchases as the UK has one of the most comprehensive sugar reduction strategies in the world.METHODS: Grocery purchase data from a nationally representative consumer panel (n=7,188) in Australia was linked with a large database (FoodSwitch) with product-specific sugar content information for packaged foods (n=25,261); both datasets were collected in 2018. Potential reductions in per capita sugar purchases were calculated overall and by food category. Differences in sugar reduction across income level were assessed by analysis of variance.RESULTS: In 2018, the total sugar acquired from packaged food and beverage purchases consumed at-home was 56.1 g/day per capita. Australia's voluntary reformulation targets for sugar covered 2,471/25,261 (9.8%) unique products in the FoodSwitch dataset. Under the scenario that all food companies adhered to the voluntary targets, sugar purchases were estimated to be reduced by 0.9 g/day per capita, which represents a 1.5% reduction in sugar purchased from packaged foods. However, if Australia adopted the UK targets, over twice as many products would be covered (n=4,667), and this would result in a more than four times greater reduction in sugar purchases (4.1 g/day per capita). It was also estimated that if all food companies complied with Australia's voluntary sugar targets, reductions to sugar would be slightly greater in low-income households compared with high-income households by 0.3 g/day (95%CI 0.2 - 0.4 g/day, p<0.001).CONCLUSIONS: Sugar-reduction policies have the potential to substantially reduce population sugar consumption and may help to reduce health inequalities related to excess sugar consumption. However, the current reformulation targets in Australia are estimated to achieve only a small reduction to sugar intakes, particularly in comparison to the UK's sugar reduction program.
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| 10. |
- Coyle, Daisy H, et al.
(författare)
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Socio-economic difference in purchases of ultra-processed foods in Australia : an analysis of a nationally representative household grocery purchasing panel.
- 2022
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Ingår i: International Journal of Behavioral Nutrition and Physical Activity. - : Springer Science and Business Media LLC. - 1479-5868. ; 19:1, s. 148-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Consumption of ultra-processed foods is associated with increased risk of obesity and non-communicable diseases. Little is known about current patterns of ultra-processed foods intake in Australia. The aim of this study was to examine the amount and type of ultra-processed foods purchased by Australian households in 2019 and determine whether purchases differed by socio-economic status (SES). We also assessed whether purchases of ultra-processed foods changed between 2015 and 2019. METHODS: We used grocery purchase data from a nationally representative consumer panel in Australia to assess packaged and unpackaged grocery purchases that were brought home between 2015 to 2019. Ultra-processed foods were identified according to the NOVA system, which classifies foods according to the nature, extent and purpose of industrial food processing. Purchases of ultra-processed foods were calculated per capita, using two outcomes: grams/day and percent of total energy. The top food categories contributing to purchases of ultra-processed foods in 2019 were identified, and differences in ultra-processed food purchases by SES (Index of Relative Social Advantage and Disadvantage) were assessed using survey-weighted linear regression. Changes in purchases of ultra-processed foods between 2015 to 2019 were examined overall and by SES using mixed linear models.RESULTS: In 2019, the mean ± SD total grocery purchases made by Australian households was 881.1 ± 511.9 g/d per capita. Of this, 424.2 ± 319.0 g/d per capita was attributable to purchases of ultra-processed foods, which represented 56.4% of total energy purchased. The largest food categories contributing to total energy purchased included mass-produced, packaged breads (8.2% of total energy purchased), chocolate and sweets (5.7%), biscuits and crackers (5.7%) and ice-cream and edible ices (4.3%). In 2019, purchases of ultra-processed foods were significantly higher for the lowest SES households compared to all other SES quintiles (P < 0.001). There were no major changes in purchases of ultra-processed foods overall or by SES over the five-year period.CONCLUSIONS: Between 2015 and 2019, ultra-processed foods have consistently made up the majority of groceries purchased by Australians, particularly for the lowest SES households. Policies that reduce ultra-processed food consumption may reduce diet-related health inequalities.
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| 11. |
- Coyle, Daisy H, et al.
(författare)
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The Contribution of Major Food Categories and Companies to Household Purchases of Added Sugar in Australia.
- 2022
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Ingår i: Journal of the Academy of Nutrition and Dietetics. - : Elsevier. - 2212-2672 .- 2212-2680. ; 122:2, s. 345-353.e3
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Australian Government will soon be releasing a series of sugar reformulation targets for packaged foods.OBJECTIVE: To estimate the amount of added sugar purchased from packaged food and beverages and the relative contribution that food categories and food companies made to these purchases in 2018. The secondary objective was to examine differences in purchases of added sugar across income levels.DESIGN: Cross-sectional study.PARTICIPANTS/SETTING: We used 1 year of grocery purchase data from a nationally representative panel of Australian households (the NielsenIQ Homescan panel), combined with a packaged food and beverage database (FoodSwitch).MAIN OUTCOME MEASURES: Added sugar purchases (grams per day per capita), purchase-weighted added sugar content (grams per 100 g) and total weight of products (with added sugar) purchased (grams per day per capita).STATISTICAL ANALYSES PERFORMED: Food categories and food companies were ranked according to their contribution to added sugar purchases. Differences in added sugar purchases by income levels were assessed by 1-factor analysis of variance.RESULTS: Added sugar information was available from 7188 households and across 26,291 unique foods and beverages. On average, the amount of added sugar acquired from packaged foods and beverages was (mean ± SE) 35.9 ± 0.01 g/d per capita. Low-income households purchased 11.0 g/d (95% CI: 10.9-11.0 g/d, P < .001) more added sugar from packaged products than high-income households per capita. The top 10 food categories accounted for 82.2% of added sugar purchased, largely due to purchases of chocolate and sweets, soft drinks, and ice cream and edible ices. Out of 994 food companies, the top 10 companies contributed to 62.1% of added sugar purchases.CONCLUSIONS: The Australian Government can strengthen their proposed sugar reduction program by adding further category-specific targets, prioritizing engagement with key food companies and considering a broader range of policies to reduce added sugar intakes across the Australian population.
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| 12. |
- Davies, Tazman, et al.
(författare)
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Packaged foods purchased on price promotion in Australia
- 2023
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Ingår i: Appetite. - : Elsevier. - 0195-6663 .- 1095-8304. ; 180
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Tidskriftsartikel (refereegranskat)abstract
- We examined the prevalence and magnitude of price promotions among purchases of packaged foods and beverages in Australia, as well as the contribution of price-promoted foods and beverages to apparent energy intake. We utilized grocery purchase data from a nationally representative panel of 10 000 households in 2019 (NielsenIQ Homescan panel), combined with a food nutrition dataset (FoodSwitch). Nutritional quality was defined using the Australian and New Zealand Health Star Rating (HSR), where products with an HSR <3.5 were classified as 'less healthy' and products with an HSR >= 3.5 were classified as 'healthy'. Apparent energy intake was expressed as the total energy content of all purchased products per day per capita. Price promotions were claimed by panel members. Overall, four-in-ten packaged products (41%) were purchased on price promotion. Compared to 'healthy' products, 'less healthy' products were more frequently purchased on price promotion (33% vs 48%, respectively, p < 0.001), but had a similar mean magnitude of price discount (both 22%). Low socio-economic status (SES) households consumed 18% more energy from 'less healthy' packaged products on price promotion than high SES households (1141 vs 970 kJ/day/capita, p < 0.001). In conclusion, restricting price promotions for 'less healthy' packaged foods and beverages could potentially improve diet quality and dietary inequalities in Australia.
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| 13. |
- Fröjmark, Anne-Sophie, et al.
(författare)
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Mutations in frizzled 6 cause isolated autosomal-recessive nail dysplasia
- 2011
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 88:6, s. 852-860
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Tidskriftsartikel (refereegranskat)abstract
- Inherited and isolated nail malformations are rare and heterogeneous conditions. We identified two consanguineous pedigrees in which some family members were affected by isolated nail dysplasia that suggested an autosomal-recessive inheritance pattern and was characterized by claw-shaped nails, onychauxis, and onycholysis. Genome-wide SNP array analysis of affected individuals from both families showed an overlapping and homozygous region of 800 kb on the long arm of chromosome 8. The candidate region spans eight genes, and DNA sequence analysis revealed homozygous nonsense and missense mutations in FZD(6), the gene encoding Frizzled 6. FZD(6) belongs to a family of highly conserved membrane-bound WNT receptors involved in developmental processes and differentiation through several signaling pathways. We expressed the FZD(6) missense mutation and observed a quantitative shift in subcellular distribution from the plasma membrane to the lysosomes, where the receptor is inaccessible for signaling and presumably degraded. Analysis of human fibroblasts homozygous for the nonsense mutation showed an aberrant response to both WNT-3A and WNT-5A stimulation; this response was consistent with an effect on both canonical and noncanonical WNT-FZD signaling. A detailed analysis of the Fzd(6)(-/-) mice, previously shown to have an altered hair pattern, showed malformed claws predominantly of the hind limbs. Furthermore, a transient Fdz6 mRNA expression was observed in the epidermis of the digital tips at embryonic day 16.5 during early claw morphogenesis. Thus, our combined results show that FZD6 mutations can result in severe defects in nail and claw formation through reduced or abolished membranous FZD(6) levels and several nonfunctional WNT-FZD pathways.
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| 14. |
- Khan, Yusra Habib, et al.
(författare)
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Barriers and facilitators of childhood COVID-19 vaccination among parents : A systematic review
- 2022
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Ingår i: Frontiers in Pediatrics. - : Frontiers Media S.A.. - 2296-2360. ; 10
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Forskningsöversikt (refereegranskat)abstract
- BackgroundThe acceptance of vaccination against COVID-19 among parents of young children plays a significant role in controlling the current pandemic. A wide range of factors that influence vaccine hesitancy in adults has been reported worldwide, but less attention has been given to COVID-19 vaccination among children. Vaccine hesitancy is considered a major challenge in achieving herd immunity, and it is more challenging among parents as they remain deeply concerned about their child's health. In this context, a systematic review of the current literature is inevitable to assess vaccine hesitancy among parents of young children to ensure a successful ongoing vaccination program.MethodA systematic search of peer-reviewed English literature indexed in Google Scholar, PubMed, Embase, and Web of science was performed using developed keywords between 1 January 2020 and August 2022. This systematic review included only those studies that focused on parental concerns about COVID-19 vaccines in children up to 12 years without a diagnosis of COVID-19. Following PRISMA guidelines, a total of 108 studies were included. The quality appraisal of the study was performed by Newcastle-Ottawa Scale (NOS).ResultsThe results of 108 studies depict that vaccine hesitancy rates differed globally with a considerably large number of factors associated with it. The highest vaccine hesitancy rates among parents were reported in a study from the USA (86.1%) and two studies from Saudi Arabia (> 85%) and Turkey (89.6%). Conversely, the lowest vaccine hesitancy rates ranging from 0.69 and 2% were found in two studies from South Africa and Switzerland, respectively. The largest study (n = 227,740) was conducted in Switzerland while the smallest sample size (n = 12) was represented by a study conducted in the USA. The most commonly reported barriers to childhood vaccination were mothers' lower education level (N = 46/108, 43%), followed by financial instability (N = 19/108, 18%), low confidence in new vaccines (N = 13/108, 12%), and unmonitored social media platforms (N = 5/108, 4.6%). These factors were significantly associated with vaccine refusal among parents. However, the potential facilitators for vaccine uptake among respondents who intended to have their children vaccinated include higher education level (N = 12/108, 11%), followed by information obtained through healthcare professionals (N = 9/108, 8.3%) and strong confidence in preventive measures taken by the government (N = 5/81, 4.6%).ConclusionThis review underscores that parents around the globe are hesitant to vaccinate their kids against COVID-19. The spectrum of factors associated with vaccine hesitancy and uptake varies across the globe. There is a dire need to address vaccine hesitancy concerns regarding the efficacy and safety of approved vaccines. Local context is inevitable to take into account while developing programs to reduce vaccine hesitancy. There is a dire need to devise strategies to address vaccine hesitancy among parents through the identification of attributing factors.
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| 15. |
- Klar, Joakim, 1974-, et al.
(författare)
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A missense variant in ITPR1 provides evidence for autosomal recessive SCA29 with asymptomatic cerebellar hypoplasia in carriers.
- 2017
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 25:7, s. 848-853
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Tidskriftsartikel (refereegranskat)abstract
- Spinocerebellar ataxias (SCA) comprise a heterogeneous group of inherited neurological disorders characterized by a range of symptoms from both cerebellar and extra cerebellar structures. We investigated the cause of autosomal recessive, congenital SCA in six affected family members from a large consanguineous family. Using whole-exome sequencing, we identified a homozygous ITPR1 missense variant [c.5360T>C; p.(L1787P)] segregating in all affected individuals. Heterozygous carriers were asymptomatic despite cerebellar hypoplasia. Variants in the ITPTR1 gene have previously been associated exclusively with autosomal dominant SCA15 and SCA29 with slow or no progression. The L1787 residue is highly conserved and the leucine to proline substitution has a predicted destabilizing effect on the protein structure. Additionally, the L1787P variant is located in a domain separated from previously described and dominant-acting missense variants consistent with a distinct effect on IP3R1 tetramer structure and function. Taken together, we show for the first time that a biallelic ITPR1 missense variant may cause an autosomal recessive and infantile onset SCA29, albeit with subclinical cerebellar hypoplasia in carriers. Our findings add to the genetic complexity of SCA29 and broaden the correlations between ITPR1 variants and their clinical expression.
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| 16. |
- Klar, Joakim, 1974-, et al.
(författare)
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Altered paracellular cation permeability due to a rare CLDN10B variant causes anhidrosis and kidney damage
- 2017
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 13:7
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Tidskriftsartikel (refereegranskat)abstract
- Claudins constitute the major component of tight junctions and regulate paracellular permeability of epithelia. Claudin-10 occurs in two major isoforms that form paracellular channels with ion selectivity. We report on two families segregating an autosomal recessive disorder characterized by generalized anhidrosis, severe heat intolerance and mild kidney failure. All affected individuals carry a rare homozygous missense mutation c.144C>G, p.(N48K) specific for the claudin-10b isoform. Immunostaining of sweat glands from patients suggested that the disease is associated with reduced levels of claudin-10b in the plasma membranes and in canaliculi of the secretory portion. Expression of claudin-10b N48K in a 3D cell model of sweat secretion indicated perturbed paracellular Na+ transport. Analysis of paracellular permeability revealed that claudin-10b N48K maintained cation over anion selectivity but with a reduced general ion conductance. Furthermore, freeze fracture electron microscopy showed that claudin-10b N48K was associated with impaired tight junction strand formation and altered cis-oligomer formation. These data suggest that claudin-10b N48K causes anhidrosis and our findings are consistent with a combined effect from perturbed TJ function and increased degradation of claudin-10b N48K in the sweat glands. Furthermore, affected individuals present with Mg2+ retention, secondary hyperparathyroidism and mild kidney failure that suggest a disturbed reabsorption of cations in the kidneys. These renal-derived features recapitulate several phenotypic aspects detected in mice with kidney specific loss of both claudin-10 isoforms. Our study adds to the spectrum of phenotypes caused by tight junction proteins and demonstrates a pivotal role for claudin-10b in maintaining paracellular Na+ permeability for sweat production and kidney function.
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| 17. |
- Kulakova, Alina, et al.
(författare)
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Chemometrics in Protein Formulation : Stability Governed by Repulsion and Protein Unfolding
- 2023
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Ingår i: Molecular Pharmaceutics. - 1543-8384. ; 20:6, s. 2951-2965
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Tidskriftsartikel (refereegranskat)abstract
- Therapeutic proteins can be challenging to develop due to their complexity and the requirement of an acceptable formulation to ensure patient safety and efficacy. To date, there is no universal formulation development strategy that can identify optimal formulation conditions for all types of proteins in a fast and reliable manner. In this work, high-throughput characterization, employing a toolbox of five techniques, was performed on 14 structurally different proteins formulated in 6 different buffer conditions and in the presence of 4 different excipients. Multivariate data analysis and chemometrics were used to analyze the data in an unbiased way. First, observed changes in stability were primarily determined by the individual protein. Second, pH and ionic strength are the two most important factors determining the physical stability of proteins, where there exists a significant statistical interaction between protein and pH/ionic strength. Additionally, we developed prediction methods by partial least-squares regression. Colloidal stability indicators are important for prediction of real-time stability, while conformational stability indicators are important for prediction of stability under accelerated stress conditions at 40 °C. In order to predict real-time storage stability, protein-protein repulsion and the initial monomer fraction are the most important properties to monitor.
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| 18. |
- Shahid, Maria, et al.
(författare)
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The effect of mycoprotein intake on biomarkers of human health : a systematic review and meta-analysis
- 2023
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Ingår i: American Journal of Clinical Nutrition. - : Oxford University Press. - 0002-9165 .- 1938-3207. ; 118:1, s. 141-150
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mycoprotein is a fungal source of protein that is increasingly consumed as an ingredient in meat analogs.Objectives: This study aimed to systematically review and meta-analyze the effects of mycoprotein intake on selected biomarkers of human health.Methods: This study was registered in PROSPERO (CRD42022308980). We searched the PubMed, Scopus, and Embase databases to identify randomized control trials in any language until 16 August, 2022. Trials were included if they administered a mycoprotein intervention against a nonmycoprotein control arm and if reported outcomes included blood lipids, blood glucose, insulin, blood pressure, or body weight. Eligible trials were assessed for risk of bias using the Cochrane risk-of-bias tool for randomized trials. An inverse-variance-weighted, random-effects meta-analysis model was used to assess the effects of intake across each biomarker.Results: Nine trials that included 178 participants with a mean follow-up of 13 d were included, with 4 reporting on blood lipids and 5 reporting on postprandial blood glucose or insulin. The overall reduction of total cholesterol was -0.55 mmol/L (95% CI: -0.85 to -0.26; P < 0.001) in the mycoprotein group compared to control, but no clear effects on HDL cholesterol, LDL cholesterol, or TGs were found (all P > 0.05). There were no reductions in postprandial blood glucose concentrations at 30, 60, 90 or 120 min. Postprandial blood insulin concentration was reduced by -76.51 pmol/L (95% CI: -150.75 to -2.28; P = 0.043) at 30 min, with no detectable effects at 60, 90, or 120 min.Conclusions: Mycoprotein intake may have important effects on blood lipids, but the evidence base is limited by the small sample sizes and short intervention periods of the contributing trials. The protocol for this systematic review has been registered in PROSPERO as CRD42022308980.
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| 19. |
- Trieu, Kathy, et al.
(författare)
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Estimated Dietary and Health Impact of the World Health Organization's Global Sodium Benchmarks on Packaged Foods in Australia : a Modeling Study.
- 2023
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Ingår i: Hypertension. - 0194-911X .- 1524-4563.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In 2021, the World Health Organization (WHO) set sodium benchmarks for packaged foods to guide countries in setting feasible and effective sodium reformulation programs. We modeled the dietary and health impact of full compliance with the WHO's sodium benchmarks in Australia and compared it to the potential impact of Australia's 2020 sodium reformulation targets.METHODS: We used nationally representative data on food and sodium intake, sodium levels in packaged foods, and food sales volume to estimate sodium intake pre- and post-implementation of the WHO and Australia's sodium benchmarks for 24 age-sex groups. Using comparative risk assessment models, we then estimated the potential deaths, incidence, and disability-adjusted life years averted from cardiovascular disease, chronic kidney disease, and stomach cancer based on the reductions in sodium intake.RESULTS: Compliance with the WHO's sodium benchmarks for packaged foods in Australia could lower mean adult sodium intake by 404 mg/day, corresponding to a 12% reduction. This could prevent about 1770 deaths/year (95% uncertainty interval 1168-2587), corresponding to 3% of all cardiovascular disease, chronic kidney disease, and stomach cancer deaths in Australia, and prevent some 6900 (4603-9513) new cases, and 25 700 (17 655-35 796) disability-adjusted life years/year. Compared with Australian targets, the WHO benchmarks will avert around 3 and a half times more deaths each year (1770 versus 510).CONCLUSIONS: Substantially greater health impact could be achieved if the Australian government strengthened its current sodium reformulation program by adopting WHO's more stringent and comprehensive sodium benchmarks.
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| 20. |
- Unterkalmsteiner, Michael, et al.
(författare)
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Software startups-A research agenda
- 2016
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Ingår i: e-Informatica Software Engineering Journal. - : Politechnika Wroclawska. - 1897-7979 .- 2084-4840. ; 10:1, s. 89-123
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Tidskriftsartikel (refereegranskat)abstract
- Software startup companies develop innovative, software-intensive products within limited time frames and with few resources, searching for sustainable and scalable business models. Software startups are quite distinct from traditional mature software companies, but also from micro-, small-, and medium-sized enterprises, introducing new challenges relevant for software engineering research. This paper's research agenda focuses on software engineering in startups, identifying, in particular, 70+ research questions in the areas of supporting startup engineering activities, startup evolution models and patterns, ecosystems and innovation hubs, human aspects in software startups, applying startup concepts in non-startup environments, and methodologies and theories for startup research. We connect and motivate this research agenda with past studies in software startup research, while pointing out possible future directions. While all authors of this research agenda have their main background in Software Engineering or Computer Science, their interest in software startups broadens the perspective to the challenges, but also to the opportunities that emerge from multi-disciplinary research. Our audience is therefore primarily software engineering researchers, even though we aim at stimulating collaborations and research that crosses disciplinary boundaries. We believe that with this research agenda we cover a wide spectrum of the software startup industry current needs.
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| 21. |
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