| 1. |
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| 2. |
- Kanoni, Stavroula, et al.
(author)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Journal article (peer-reviewed)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. |
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| 4. |
- Bousquet, Jean, et al.
(author)
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ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice
- 2021
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In: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:1, s. 168-190
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Research review (peer-reviewed)abstract
- Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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| 5. |
- Reinke, Beth A, et al.
(author)
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Diverse aging rates in ectothermic tetrapods provide insights for the evolution of aging and longevity
- 2022
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In: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 376:6600, s. 1459-1466
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Journal article (peer-reviewed)abstract
- Comparative studies of mortality in the wild are necessary to understand the evolution of aging; yet, ectothermic tetrapods are underrepresented in this comparative landscape, despite their suitability for testing evolutionary hypotheses. We present a study of aging rates and longevity across wild tetrapod ectotherms, using data from 107 populations (77 species) of nonavian reptiles and amphibians. We test hypotheses of how thermoregulatory mode, environmental temperature, protective phenotypes, and pace of life history contribute to demographic aging. Controlling for phylogeny and body size, ectotherms display a higher diversity of aging rates compared with endotherms and include phylogenetically widespread evidence of negligible aging. Protective phenotypes and life-history strategies further explain macroevolutionary patterns of aging. Analyzing ectothermic tetrapods in a comparative context enhances our understanding of the evolution of aging.
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| 6. |
- Bousquet, J. Jean, et al.
(author)
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Next-generation ARIA care pathways for rhinitis and asthma : a model for multimorbid chronic diseases
- 2019
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In: Clinical and Translational Allergy. - : BMC. - 2045-7022. ; 9
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Research review (peer-reviewed)abstract
- Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.Main body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Sante as a Good Practice in the field of digitally-enabled, integrated, person-centred care.Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
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| 7. |
- Bouwmeester, S, et al.
(author)
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Registered Replication Report: Rand, Greene, and Nowak (2012) : Multilab direct replication of: Study 7 from Rand, D. G., Greene, J. D., & Nowak, M. A. (2012) Spontaneous giving and calculated greed. Nature, 489, 427–430.
- 2017
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In: Perspectives on Psychological Science. - : Sage Publications. - 1745-6916 .- 1745-6924. ; 12:3, s. 527-542
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Journal article (peer-reviewed)abstract
- In an anonymous 4-person economic game, participants contributed more money to a common project (i.e., cooperated) when required to decide quickly than when forced to delay their decision (Rand, Greene & Nowak, 2012), a pattern consistent with the social heuristics hypothesis proposed by Rand and colleagues. The results of studies using time pressure have been mixed, with some replication attempts observing similar patterns (e.g., Rand et al., 2014) and others observing null effects (e.g., Tinghög et al., 2013; Verkoeijen & Bouwmeester, 2014). This Registered Replication Report (RRR) assessed the size and variability of the effect of time pressure on cooperative decisions by combining 21 separate, preregistered replications of the critical conditions from Study 7 of the original article (Rand et al., 2012). The primary planned analysis used data from all participants who were randomly assigned to conditions and who met the protocol inclusion criteria (an intent-to-treat approach that included the 65.9% of participants in the time-pressure condition and 7.5% in the forced-delay condition who did not adhere to the time constraints), and we observed a difference in contributions of −0.37 percentage points compared with an 8.6 percentage point difference calculated from the original data. Analyzing the data as the original article did, including data only for participants who complied with the time constraints, the RRR observed a 10.37 percentage point difference in contributions compared with a 15.31 percentage point difference in the original study. In combination, the results of the intent-to-treat analysis and the compliant-only analysis are consistent with the presence of selection biases and the absence of a causal effect of time pressure on cooperation.
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| 8. |
- Bouwmeester, Sjoerd, et al.
(author)
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Registered Replication Report : Rand, Greene, and Nowak (2012)
- 2017
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In: Perspectives on Psychological Science. - : SAGE Publications. - 1745-6916 .- 1745-6924. ; 12:3, s. 527-542
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Journal article (peer-reviewed)abstract
- In an anonymous 4-person economic game, participants contributed more money to a common project (i.e., cooperated) when required to decide quickly than when forced to delay their decision (Rand, Greene & Nowak, 2012), a pattern consistent with the social heuristics hypothesis proposed by Rand and colleagues. The results of studies using time pressure have been mixed, with some replication attempts observing similar patterns (e.g., Rand et al., 2014) and others observing null effects (e.g., Tinghög et al., 2013; Verkoeijen & Bouwmeester, 2014). This Registered Replication Report (RRR) assessed the size and variability of the effect of time pressure on cooperative decisions by combining 21 separate, preregistered replications of the critical conditions from Study 7 of the original article (Rand et al., 2012). The primary planned analysis used data from all participants who were randomly assigned to conditions and who met the protocol inclusion criteria (an intent-to-treat approach that included the 65.9% of participants in the time-pressure condition and 7.5% in the forced-delay condition who did not adhere to the time constraints), and we observed a difference in contributions of −0.37 percentage points compared with an 8.6 percentage point difference calculated from the original data. Analyzing the data as the original article did, including data only for participants who complied with the time constraints, the RRR observed a 10.37 percentage point difference in contributions compared with a 15.31 percentage point difference in the original study. In combination, the results of the intent-to-treat analysis and the compliant-only analysis are consistent with the presence of selection biases and the absence of a causal effect of time pressure on cooperation.
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| 9. |
- Farnocchia, Davide, et al.
(author)
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International Asteroid Warning Network Timing Campaign: 2019 XS
- 2022
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In: The Planetary Science Journal. - : Institute of Physics Publishing (IOPP). - 2632-3338. ; 3:7
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Journal article (peer-reviewed)abstract
- As part of the International Asteroid Warning Network's observational exercises, we conducted a campaign to observe near-Earth asteroid 2019 XS around its close approach to Earth on 2021 November 9. The goal of the campaign was to characterize errors in the observation times reported to the Minor Planet Center, which become an increasingly important consideration as astrometric accuracy improves and more fast-moving asteroids are observed. As part of the exercise, a total of 957 astrometric observations of 2019 XS during the encounter were reported and subsequently were analyzed to obtain the corresponding residuals. While the timing errors are typically smaller than 1 s, the reported times appear to be negatively biased, i.e., they are generally earlier than they should be. We also compared the observer-provided position uncertainty with the cross-track residuals, which are independent of timing errors. A large fraction of the estimated uncertainties appear to be optimistic, especially when <0 2. We compiled individual reports for each observer to help identify and remove the root cause of any possible timing error and improve the uncertainty quantification process. We suggest possible sources of timing errors and describe a simple procedure to derive reliable, conservative position uncertainties.
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| 10. |
- Farnocchia, Davide, et al.
(author)
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The Second International Asteroid Warning Network Timing Campaign: 2005 LW3
- 2023
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In: The Planetary Science Journal. - : Institute of Physics (IOP). - 2632-3338. ; 4:11
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Journal article (peer-reviewed)abstract
- The Earth close approach of near-Earth asteroid 2005 LW3 on 2022 November 23 represented a good opportunity for a second observing campaign to test the timing accuracy of astrometric observation. With 82 participating stations, the International Asteroid Warning Network collected 1046 observations of 2005 LW3 around the time of the close approach. Compared to the previous timing campaign targeting 2019 XS, some individual observers were able to significantly improve the accuracy of their reported observation times. In particular, U.S. surveys achieved good timing performance. However, no broad, systematic improvement was achieved compared to the previous campaign, with an overall negative bias persisting among the different observers. The calibration of observing times and the mitigation of timing errors should be important future considerations for observers and orbit computers, respectively.
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| 11. |
- Noble, Daniel W.A., et al.
(author)
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Data Descriptor : A comprehensive database of thermal developmental plasticity in reptiles
- 2018
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In: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 5
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Journal article (peer-reviewed)abstract
- How temperature influences development has direct relevance to ascertaining the impact of climate change on natural populations. Reptiles have served as empirical models for understanding how the environment experienced by embryos can influence phenotypic variation, including sex ratio, phenology and survival. Such an understanding has important implications for basic eco-evolutionary theory and conservation efforts worldwide. While there is a burgeoning empirical literature of experimental manipulations of embryonic thermal environments, addressing widespread patterns at a comparative level has been hampered by the lack of accessible data in a format that is amendable to updates as new studies emerge. Here, we describe a database with nearly 10, 000 phenotypic estimates from 155 species of reptile, collected from 300 studies manipulating incubation temperature (published between 1974-2016). The data encompass various morphological, physiological, behavioural and performance traits along with growth rates, developmental timing, sex ratio and survival (e.g., hatching success). This resource will serve as an important data repository for addressing overarching questions about thermal plasticity of reptile embryos.
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| 12. |
- While, Geoffrey M., et al.
(author)
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Patterns of developmental plasticity in response to incubation temperature in reptiles
- 2018
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In: Journal of Experimental Zoology Part A: Ecological and Integrative Physiology. - : Wiley. - 2471-5638 .- 2471-5646. ; 329:4-5, s. 162-176
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Journal article (peer-reviewed)abstract
- Early life environments shape phenotypic development in important ways that can lead to long-lasting effects on phenotype and fitness. In reptiles, one aspect of the early environment that impacts development is temperature (termed 'thermal developmental plasticity'). Indeed, the thermal environment during incubation is known to influence morphological, physiological, and behavioral traits, some of which have important consequences for many ecological and evolutionary processes. Despite this, few studies have attempted to synthesize and collate data from this expansive and important body of research. Here, we systematically review research into thermal developmental plasticity across reptiles, structured around the key papers and findings that have shaped the field over the past 50 years. From these papers, we introduce a large database (the 'Reptile Development Database') consisting of 9,773 trait means across 300 studies examining thermal developmental plasticity. This dataset encompasses data on a range of phenotypes, including morphological, physiological, behavioral, and performance traits along with growth rate, incubation duration, sex ratio, and survival (e.g., hatching success) across all major reptile clades. Finally, from our literature synthesis and data exploration, we identify key research themes associated with thermal developmental plasticity, important gaps in empirical research, and demonstrate how future progress can be made through targeted empirical, meta-analytic, and comparative work.
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| 13. |
- Kahrl, Ariel F., et al.
(author)
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Selection on Sperm Count, but Not on Sperm Morphology or Velocity, in a Wild Population of Anolis Lizards
- 2021
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In: Cells. - : MDPI AG. - 2073-4409. ; 10:9
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Journal article (peer-reviewed)abstract
- Sperm competition is a widespread phenomenon that shapes male reproductive success. Ejaculates present many potential targets for postcopulatory selection (e.g., sperm morphology, count, and velocity), which are often highly correlated and potentially subject to complex multivariate selection. Although multivariate selection on ejaculate traits has been observed in laboratory experiments, it is unclear whether selection is similarly complex in wild populations, where individuals mate frequently over longer periods of time. We measured univariate and multivariate selection on sperm morphology, sperm count, and sperm velocity in a wild population of brown anole lizards (Anolis sagrei). We conducted a mark-recapture study with genetic parentage assignment to estimate individual reproductive success. We found significant negative directional selection and negative quadratic selection on sperm count, but we did not detect directional or quadratic selection on any other sperm traits, nor did we detect correlational selection on any trait combinations. Our results may reflect pressure on males to produce many small ejaculates and mate frequently over a six-month reproductive season. This study is the first to measure multivariate selection on sperm traits in a wild population and provides an interesting contrast to experimental studies of external fertilizers, which have found complex multivariate selection on sperm phenotypes.
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| 14. |
- Oikonomou, Vasileios, et al.
(author)
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The Role of Interferon-γ in Autoimmune Polyendocrine Syndrome Type 1.
- 2024
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In: The New England journal of medicine. - 1533-4406. ; 390:20, s. 1873-1884
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Journal article (peer-reviewed)abstract
- Autoimmune polyendocrine syndrome type 1 (APS-1) is a life-threatening, autosomal recessive syndrome caused by autoimmune regulator (AIRE) deficiency. In APS-1, self-reactive T cells escape thymic negative selection, infiltrate organs, and drive autoimmune injury. The effector mechanisms governing T-cell-mediated damage in APS-1 remain poorly understood.We examined whether APS-1 could be classified as a disease mediated by interferon-γ. We first assessed patients with APS-1 who were participating in a prospective natural history study and evaluated mRNA and protein expression in blood and tissues. We then examined the pathogenic role of interferon-γ using Aire-/-Ifng-/- mice and Aire-/- mice treated with the Janus kinase (JAK) inhibitor ruxolitinib. On the basis of our findings, we used ruxolitinib to treat five patients with APS-1 and assessed clinical, immunologic, histologic, transcriptional, and autoantibody responses.Patients with APS-1 had enhanced interferon-γ responses in blood and in all examined autoimmunity-affected tissues. Aire-/- mice had selectively increased interferon-γ production by T cells and enhanced interferon-γ, phosphorylated signal transducer and activator of transcription 1 (pSTAT1), and CXCL9 signals in multiple organs. Ifng ablation or ruxolitinib-induced JAK-STAT blockade in Aire-/- mice normalized interferon-γ responses and averted T-cell infiltration and damage in organs. Ruxolitinib treatment of five patients with APS-1 led to decreased levels of T-cell-derived interferon-γ, normalized interferon-γ and CXCL9 levels, and remission of alopecia, oral candidiasis, nail dystrophy, gastritis, enteritis, arthritis, Sjögren's-like syndrome, urticaria, and thyroiditis. No serious adverse effects from ruxolitinib were identified in these patients.Our findings indicate that APS-1, which is caused by AIRE deficiency, is characterized by excessive, multiorgan interferon-γ-mediated responses. JAK inhibition with ruxolitinib in five patients showed promising results. (Funded by the National Institute of Allergy and Infectious Diseases and others.).
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| 15. |
- Fargevieille, Amélie, et al.
(author)
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Propagule size and sex ratio influence colonisation dynamics after introduction of a non-native lizard
- 2022
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In: Journal of Animal Ecology. - : Wiley. - 0021-8790 .- 1365-2656. ; 91:4, s. 845-857
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Journal article (peer-reviewed)abstract
- The composition of founding populations plays an important role in colonisation dynamics and can influence population growth during early stages of biological invasion. Specifically, founding populations with small propagules (i.e. low number of founders) are vulnerable to the Allee effect and have reduced likelihood of establishment compared to those with large propagules. The founding sex ratio can also impact establishment via its influence on mating success and offspring production.Our goal was to test the effects of propagule size and sex ratio on offspring production and annual population growth following introductions of a non-native lizard species (Anolis sagrei). We manipulated propagule composition on nine small islands, then examined offspring production, population growth and survival rate of founders and their descendants encompassing three generations.By the third reproductive season, per capita offspring production was higher on islands seeded with a relatively large propagule size, but population growth was not associated with propagule size. Propagule sex ratio did not affect offspring production, but populations with a female-biased propagule had positive growth, whereas those with a male-biased propagule had negative growth in the first year. Populations were not affected by propagule sex ratio in subsequent years, possibly due to rapid shifts towards balanced (or slightly female biased) population sex ratios.Overall, we show that different components of population fitness have different responses to propagule size and sex ratio in ways that could affect early stages of biological invasion. Despite these effects, the short life span and high fecundity of A. sagrei likely helped small populations to overcome Allee effects and enabled all populations to successfully establish.Our rare experimental manipulation of propagule size and sex ratio can inform predictions of colonisation dynamics in response to different compositions of founding populations, which is critical in the context of population ecology and invasion dynamics.
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| 16. |
- Kotz, Kenneth T., et al.
(author)
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Clinical microfluidics for neutrophil genomics and proteomics
- 2010
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 16:9, s. 1042-U142
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Journal article (peer-reviewed)abstract
- Neutrophils have key roles in modulating the immune response. We present a robust methodology for rapidly isolating neutrophils directly from whole blood with 'on-chip' processing for mRNA and protein isolation for genomics and proteomics. We validate this device with an ex vivo stimulation experiment and by comparison with standard bulk isolation methodologies. Last, we implement this tool as part of a near-patient blood processing system within a multi-center clinical study of the immune response to severe trauma and burn injury. The preliminary results from a small cohort of subjects in our study and healthy controls show a unique time-dependent gene expression pattern clearly demonstrating the ability of this tool to discriminate temporal transcriptional events of neutrophils within a clinical setting.
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| 17. |
- Kustra, Matthew C., et al.
(author)
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Sperm morphology and count vary with fine-scale changes in local density in a wild lizard population
- 2019
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In: Oecologia. - : Springer Science and Business Media LLC. - 0029-8549 .- 1432-1939. ; 191:3, s. 555-564
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Journal article (peer-reviewed)abstract
- Given that sperm production can be costly, theory predicts that males should optimally adjust the quantity and/or quality of their sperm in response to their social environment to maximize their paternity success. Although experiments demonstrate that males can alter their ejaculates in response to manipulations of the social environment and studies show that ejaculate traits covary with social environment across populations, it is unknown whether individual variation in sperm traits corresponds to natural variation found within wild populations. Using an island population of brown anole lizards (Anolis sagrei), we tested the prediction that sperm traits (sperm count, sperm morphology, sperm velocity) respond to natural variation in the risk of sperm competition, as inferred from the local density and operational sex ratio (OSR) of conspecifics. We found that males living in high-density areas of the island produced relatively larger sperm midpieces, smaller sperm heads, and lower sperm counts. Sperm traits were unrelated to OSR after accounting for the covariance between OSR and density. Our findings broaden the implications of sperm competition theory to intrapopulation social environment variation by showing that sperm count and sperm morphology vary with fine-scale differences in density within a single wild population.
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