| 1. |
- 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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| 2. |
- Lagou, Vasiliki, et al.
(författare)
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Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
- 2021
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
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| 3. |
- Alexander, Stephen P. H., et al.
(författare)
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The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors
- 2023
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Ingår i: BRITISH JOURNAL OF PHARMACOLOGY. - : British pharmacological society. - 0007-1188 .- 1476-5381. ; 180
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Tidskriftsartikel (refereegranskat)abstract
- The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at . G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
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| 4. |
- Christopoulos, Arthur, et al.
(författare)
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THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors.
- 2021
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Ingår i: British journal of pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 178 Suppl 1
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Forskningsöversikt (refereegranskat)abstract
- The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
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| 5. |
- Festari, Cristina, et al.
(författare)
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European consensus for the diagnosis of MCI and mild dementia : Preparatory phase
- 2023
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Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:5, s. 1729-1741
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Etiological diagnosis of neurocognitive disorders of middle-old age relies on biomarkers, although evidence for their rational use is incomplete. A European task force is defining a diagnostic workflow where expert experience fills evidence gaps for biomarker validity and prioritization. We report methodology and preliminary results. Methods: Using a Delphi consensus method supported by a systematic literature review, 22 delegates from 11 relevant scientific societies defined workflow assumptions. Results: We extracted diagnostic accuracy figures from literature on the use of biomarkers in the diagnosis of main forms of neurocognitive disorders. Supported by this evidence, panelists defined clinical setting (specialist outpatient service), application stage (MCI-mild dementia), and detailed pre-assessment screening (clinical-neuropsychological evaluations, brain imaging, and blood tests). Discussion: The Delphi consensus on these assumptions set the stage for the development of the first pan-European workflow for biomarkers’ use in the etiological diagnosis of middle-old age neurocognitive disorders at MCI-mild dementia stages. Highlights: Rational use of biomarkers in neurocognitive disorders lacks consensus in Europe. A consensus of experts will define a workflow for the rational use of biomarkers. The diagnostic workflow will be patient-centered and based on clinical presentation. The workflow will be updated as new evidence accrues.
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| 6. |
- Frisoni, Giovanni B., et al.
(författare)
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European intersocietal recommendations for the biomarker-based diagnosis of neurocognitive disorders
- 2024
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Ingår i: The Lancet Neurology. - 1474-4422 .- 1474-4465. ; 23:3, s. 302-312
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Forskningsöversikt (refereegranskat)abstract
- The recent commercialisation of the first disease-modifying drugs for Alzheimer's disease emphasises the need for consensus recommendations on the rational use of biomarkers to diagnose people with suspected neurocognitive disorders in memory clinics. Most available recommendations and guidelines are either disease-centred or biomarker-centred. A European multidisciplinary taskforce consisting of 22 experts from 11 European scientific societies set out to define the first patient-centred diagnostic workflow that aims to prioritise testing for available biomarkers in individuals attending memory clinics. After an extensive literature review, we used a Delphi consensus procedure to identify 11 clinical syndromes, based on clinical history and examination, neuropsychology, blood tests, structural imaging, and, in some cases, EEG. We recommend first-line and, if needed, second-line testing for biomarkers according to the patient's clinical profile and the results of previous biomarker findings. This diagnostic workflow will promote consistency in the diagnosis of neurocognitive disorders across European countries.
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| 7. |
- van de Vegte, Yordi, et al.
(författare)
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Genetic insights into resting heart rate and its role in cardiovascular disease
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
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| 8. |
- Awan, Iqra Zubair, et al.
(författare)
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Composition Effect on the Formation of Oxide Phases by Thermal Decomposition of CuNiM(III) Layered Double Hydroxides with M(III) = Al, Fe
- 2024
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Ingår i: Materials. - 1996-1944. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- The thermal decomposition processes of coprecipitated Cu-Ni-Al and Cu-Ni-Fe hydroxides and the formation of the mixed oxide phases were followed by thermogravimetry and derivative thermogravimetry analysis (TG – DTG) and in situ X-ray diffraction (XRD) in a temperature range from 25 to 800 °C. The as-prepared samples exhibited layered double hydroxide (LDH) with a rhombohedral structure for the Ni-richer Al- and Fe-bearing LDHs and a monoclinic structure for the CuAl LDH. Direct precipitation of CuO was also observed for the Cu-richest Fe-bearing samples. After the collapse of the LDHs, dehydration, dehydroxylation, and decarbonation occurred with an overlapping of these events to an extent, depending on the structure and composition, being more pronounced for the Fe-bearing rhombohedral LDHs and the monoclinic LDH. The Fe-bearing amorphous phases showed higher reactivity than the Al-bearing ones toward the crystallization of the mixed oxide phases. This reactivity was improved as the amount of embedded divalent cations increased. Moreover, the influence of copper was effective at a lower content than that of nickel.
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| 9. |
- Cuzzubbo, Stefania, et al.
(författare)
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Cancer Vaccines : Adjuvant Potency, Importance of Age, Lifestyle, and Treatments
- 2021
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 11
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Forskningsöversikt (refereegranskat)abstract
- Although the discovery and characterization of multiple tumor antigens have sparked the development of many antigen/derived cancer vaccines, many are poorly immunogenic and thus, lack clinical efficacy. Adjuvants are therefore incorporated into vaccine formulations to trigger strong and long-lasting immune responses. Adjuvants have generally been classified into two categories: those that 'depot' antigens (e.g. mineral salts such as aluminum hydroxide, emulsions, liposomes) and those that act as immunostimulants (Toll Like Receptor agonists, saponins, cytokines). In addition, several novel technologies using vector-based delivery of antigens have been used. Unfortunately, the immune system declines with age, a phenomenon known as immunosenescence, and this is characterized by functional changes in both innate and adaptive cellular immunity systems as well as in lymph node architecture. While many of the immune functions decline over time, others paradoxically increase. Indeed, aging is known to be associated with a low level of chronic inflammation-inflamm-aging. Given that the median age of cancer diagnosis is 66 years and that immunotherapeutic interventions such as cancer vaccines are currently given in combination with or after other forms of treatments which themselves have immune-modulating potential such as surgery, chemotherapy and radiotherapy, the choice of adjuvants requires careful consideration in order to achieve the maximum immune response in a compromised environment. In addition, more clinical trials need to be performed to carefully assess how less conventional form of immune adjuvants, such as exercise, diet and psychological care which have all be shown to influence immune responses can be incorporated to improve the efficacy of cancer vaccines. In this review, adjuvants will be discussed with respect to the above-mentioned important elements.
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| 10. |
- Deane, C. S., et al.
(författare)
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Space omics research in Europe : Contributions, geographical distribution and ESA member state funding schemes
- 2022
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Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 25:3, s. 103920-
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Tidskriftsartikel (refereegranskat)abstract
- The European research community, via European Space Agency (ESA) spaceflight opportunities, has significantly contributed toward our current understanding of spaceflight biology. Recent molecular biology experiments include “omic” analysis, which provides a holistic and systems level understanding of the mechanisms underlying phenotypic adaptation. Despite vast interest in, and the immense quantity of biological information gained from space omics research, the knowledge of ESA-related space omics works as a collective remains poorly defined due to the recent exponential application of omics approaches in space and the limited search capabilities of pre-existing records. Thus, a review of such contributions is necessary to clarify and promote the development of space omics among ESA and ESA state members. To address this gap, in this review, we i) identified and summarized omics works led by European researchers, ii) geographically described these omics works, and iii) highlighted potential caveats in complex funding scenarios among ESA member states.
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