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| 4. |
- Santangelo, James S., et al.
(author)
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Global urban environmental change drives adaptation in white clover
- 2022
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
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Journal article (peer-reviewed)abstract
- Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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| 5. |
- Liu, Kui, et al.
(author)
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Kallikrein genes are associated with lupus and glomerular basement membrane-specific antibody-induced nephritis in mice and humans
- 2009
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In: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 119:4, s. 911-923
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Journal article (peer-reviewed)abstract
- Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody-induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that maybe responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody-induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family,which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody-induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms,some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody-induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody-induced nephritis and lupus.
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| 6. |
- Jami, E. S., et al.
(author)
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Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms
- 2022
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In: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567 .- 1527-5418. ; 61:7, s. 934-945
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Journal article (peer-reviewed)abstract
- Objective: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence. Method: In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument. Results: The meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84-2.48%, n(effective) = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%-8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (vertical bar r(g)vertical bar > 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range vertical bar r(g)vertical bar = 0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. Conclusion: Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.
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| 7. |
- Leebens-Mack, James H., et al.
(author)
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One thousand plant transcriptomes and the phylogenomics of green plants
- 2019
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In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7780, s. 679-
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Journal article (peer-reviewed)abstract
- Green plants (Viridiplantae) include around 450,000-500,000 species(1,2) of great diversity and have important roles in terrestrial and aquatic ecosystems. Here, as part of the One Thousand Plant Transcriptomes Initiative, we sequenced the vegetative transcriptomes of 1,124 species that span the diversity of plants in a broad sense (Archaeplastida), including green plants (Viridiplantae), glaucophytes (Glaucophyta) and red algae (Rhodophyta). Our analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported across multiple species tree and supermatrix analyses, but discordance among plastid and nuclear gene trees at a few important nodes highlights the complexity of plant genome evolution, including polyploidy, periods of rapid speciation, and extinction. Incomplete sorting of ancestral variation, polyploidization and massive expansions of gene families punctuate the evolutionary history of green plants. Notably, we find that large expansions of gene families preceded the origins of green plants, land plants and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of flowering plants and ferns. The increasing availability of high-quality plant genome sequences and advances in functional genomics are enabling research on genome evolution across the green tree of life.
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| 8. |
- Thompson, PM, et al.
(author)
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ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries
- 2020
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In: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 10:1, s. 100-
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Journal article (peer-reviewed)abstract
- This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of “big data” (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA’s activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.
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| 9. |
- Stack, K. M., et al.
(author)
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Sedimentology and Stratigraphy of the Shenandoah Formation, Western Fan, Jezero Crater, Mars
- 2024
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In: Journal of Geophysical Research: Planets. - 2169-9097. ; 129:2
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Journal article (peer-reviewed)abstract
- Sedimentary fans are key targets of exploration on Mars because they record the history of surface aqueous activity and habitability. The sedimentary fan extending from the Neretva Vallis breach of Jezero crater's western rim is one of the Mars 2020 Perseverance rover's main exploration targets. Perseverance spent ∼250 sols exploring and collecting seven rock cores from the lower ∼25 m of sedimentary rock exposed within the fan's eastern scarp, a sequence informally named the “Shenandoah” formation. This study describes the sedimentology and stratigraphy of the Shenandoah formation at two areas, “Cape Nukshak” and “Hawksbill Gap,” including a characterization, interpretation, and depositional framework for the facies that comprise it. The five main facies of the Shenandoah formation include: laminated mudstone, laminated sandstone, low-angle cross stratified sandstone, thin-bedded granule sandstone, and thick-bedded granule-pebble sandstone and conglomerate. These facies are organized into three facies associations (FA): FA1, comprised of laminated and soft sediment-deformed sandstone interbedded with broad, unconfined coarser-grained granule and pebbly sandstone intervals; FA2, comprised predominantly of laterally extensive, soft-sediment deformed laminated, sulfate-bearing mudstone with lenses of low-angle cross-stratified and scoured sandstone; and FA3, comprised of dipping planar, thin-bedded sand-gravel couplets. The depositional model favored for the Shenandoah formation involves the transition from a sand-dominated distal alluvial fan setting (FA1) to a stable, widespread saline lake (FA2), followed by the progradation of a river delta system (FA3) into the lake basin. This sequence records the initiation of a relatively long-lived, habitable lacustrine and deltaic environment within Jezero crater.
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| 10. |
- Boutet, S., et al.
(author)
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High-Resolution Protein Structure Determination by Serial Femtosecond Crystallography
- 2012
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 337:6092, s. 362-364
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Journal article (peer-reviewed)abstract
- Structure determination of proteins and other macromolecules has historically required the growth of high-quality crystals sufficiently large to diffract x-rays efficiently while withstanding radiation damage. We applied serial femtosecond crystallography (SFX) using an x-ray free-electron laser (XFEL) to obtain high-resolution structural information from microcrystals (less than 1 micrometer by 1 micrometer by 3 micrometers) of the well-characterized model protein lysozyme. The agreement with synchrotron data demonstrates the immediate relevance of SFX for analyzing the structure of the large group of difficult-to-crystallize molecules.
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| 11. |
- Ahmed, S., et al.
(author)
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The economic burden of rotavirus hospitalization among children < 5 years of age in selected hospitals in Bangladesh
- 2021
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In: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 39:48, s. 7082-7090
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Journal article (peer-reviewed)abstract
- Background: Rotavirus is a common cause of severe acute gastroenteritis among young children. Estimation of the economic burden would provide informed decision about investment on prevention strategies (e.g., vaccine and/or behavior change), which has been a potential policy discussion in Bangladesh for several years. Methods: We estimated the societal costs of children <5 years for hospitalization from rotavirus gastroenteritis (RVGE) and incidences of catastrophic health expenditure. A total of 360 children with stool specimens positive for rotavirus were included in this study from 6 tertiary hospitals (3 public and 3 private). We interviewed the caregiver of the patient and hospital staff to collect cost from patient and health facility perspectives. We estimated the economic cost considering 2015 as the reference year. Results: The total societal per-patient costs to treat RVGE in the public hospital were 126 USD (95% CI: 116-136) and total household costs were 161 USD (95% CI: 145-177) in private facilities. Direct costs constituted 38.1% of total household costs. The out-of-pocket payments for RVGE hospitalization was 23% of monthly income and 76% of households faced catastrophic healthcare expenditures due to this expense. The estimated total annual household treatment cost for the country was 10 million USD. Conclusions: A substantial economic burden of RVGE in Bangladesh was observed in this study. Any prevention of RVGE through cost-effective vaccination or/and behavioural change would contribute to substantial economic benefits to Bangladesh. (c) 2021 Elsevier Ltd. All rights reserved.
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| 12. |
- Chaplin, E., et al.
(author)
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Severe mental illness, common mental disorders, and neurodevelopmental conditions amongst 9088 lower court attendees in London, UK
- 2022
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In: Bmc Psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 22:1
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Journal article (peer-reviewed)abstract
- Background Court Mental Health Liaison and Diversion Services (CMHLDS) have developed in some countries as a response to the over-representation of mental illness and other vulnerabilities amongst defendants presenting to criminal justice (or correctional) systems. This study examined the characteristics and rates of mental disorder of 9088 defendants referred to CMHLDS. Method The study analysed service level data, obtained from the National Health Service's mental health data set, to examine characteristics relating to gender, ethnicity and comorbidity of common mental and neurodevelopmental disorders at five CMHLDS across London between September 2015 and April 2017. Results The sample included 7186 males (79.1%) and 1719 females (18.9%), the gender of 183 (2%) were not recorded. Of those referred, 6616 (72.8%) presented with an identifiable mental disorder and 503 (5.5%) with a neurodevelopmental disorder (NDD). Significantly higher rates of schizophrenia were reported amongst Black defendants (n = 681; 37.2%) and Asian defendants (n = 315; 29%), while higher rates of depression were found amongst White defendants (n = 1007; 22.1%). Substance misuse was reported amongst 2813 defendants (31%), and alcohol misuse amongst 2111 (23.2%), with significantly high rates of substance and alcohol misuse amongst defendants presenting with schizophrenia or personality disorder. Conclusions This is one of the largest studies to examine mental health needs and vulnerabilities amongst defendants presenting to CMHLDS. It will enable an improved understanding of the required service designs and resources required to manage the healthcare pathways for people attending CMHLDS.
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| 16. |
- Hillier, J. K., et al.
(author)
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Manual mapping of drumlins in synthetic landscapes to assess operator effectiveness
- 2015
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In: Journal of Maps. - : Informa UK Limited. - 1744-5647. ; 11:5, s. 719-729
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Journal article (peer-reviewed)abstract
- Mapped topographic features are important for understanding processes that sculpt the Earth's surface. This paper presents maps that are the primary product of an exercise that brought together 27 researchers with an interest in landform mapping wherein the efficacy and causes of variation in mapping were tested using novel synthetic DEMs containing drumlins. The variation between interpreters (e.g. mapping philosophy, experience) and across the study region (e.g. woodland prevalence) opens these factors up to assessment. A priori known answers in the synthetics increase the number and strength of conclusions that may be drawn with respect to a traditional comparative study. Initial results suggest that overall detection rates are relatively low (34-40%), but reliability of mapping is higher (72-86%). The maps form a reference dataset.
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| 17. |
- Litvak, M.L., et al.
(author)
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Local variations of bulk hydrogen and chlorine-equivalent neutron absorption content measured at the contact between the Sheepbed and Gillespie Lake units in Yellowknife Bay, Gale Crater, using the DAN instrument onboard Curiosity
- 2014
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In: Journal of Geophysical Research - Planets. - 2169-9097 .- 2169-9100. ; 119:6, s. 1259-1275
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Journal article (peer-reviewed)abstract
- Data gathered with the Dynamic Albedo of Neutron (DAN) instrument onboard rover Curiosity were analyzed for variations in subsurface neutron flux and tested for possible correlation with local geological context. A special DAN observation campaign was executed, in which 18 adjacent DAN active measurements were acquired every 0.75–1.0 m to search for the variations of subsurface hydrogen content along a 15 m traverse across geologic contacts between the Sheepbed and Gillespie Lake members of the Yellowknife Bay formation. It was found that several subunits in Sheepbed and Gillespie Lake could be characterized with different depth distributions of water-equivalent hydrogen (WEH) and different chlorine-equivalent abundance responsible for the distribution of neutron absorption elements. The variations of the average WEH at the top 60 cm of the subsurface are estimated at up to 2–3%. Chlorine-equivalent neutron absorption abundances ranged within 0.8–1.5%. The largest difference in WEH and chlorine-equivalent neutron absorption distribution is found between Sheepbed and Gillespie Lake.
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| 18. |
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| 19. |
- Messner, Christoph B., et al.
(author)
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Ultra-fast proteomics with Scanning SWATH
- 2021
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In: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 39:7, s. 846-854
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Journal article (peer-reviewed)abstract
- Accurate quantification of the proteome remains challenging for large sample series and longitudinal experiments. We report a data-independent acquisition method, Scanning SWATH, that accelerates mass spectrometric (MS) duty cycles, yielding quantitative proteomes in combination with short gradients and high-flow (800 µl min ) chromatography. Exploiting a continuous movement of the precursor isolation window to assign precursor masses to tandem mass spectrometry (MS/MS) fragment traces, Scanning SWATH increases precursor identifications by ~70% compared to conventional data-independent acquisition (DIA) methods on 0.5–5-min chromatographic gradients. We demonstrate the application of ultra-fast proteomics in drug mode-of-action screening and plasma proteomics. Scanning SWATH proteomes capture the mode of action of fungistatic azoles and statins. Moreover, we confirm 43 and identify 11 new plasma proteome biomarkers of COVID-19 severity, advancing patient classification and biomarker discovery. Thus, our results demonstrate a substantial acceleration and increased depth in fast proteomic experiments that facilitate proteomic drug screens and clinical studies. –1
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| 20. |
- Sanchez, E, et al.
(author)
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Effects of Amerindian Genetic Ancestry on Clinical Variables and Therapy in Patients with Rheumatoid Arthritis
- 2017
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In: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 44:12, s. 1804-1812
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Journal article (peer-reviewed)abstract
- To define whether Amerindian genetic ancestry correlates with clinical and therapeutic variables in admixed individuals with rheumatoid arthritis (RA) from Latin America.Methods.Patients with RA (n = 1347) and healthy controls (n = 1012) from Argentina, Mexico, Chile, and Peru were included. Samples were genotyped for the Immunochip v1 using the Illumina platform. Clinical data were obtained through interviews or the clinical history.Results.Percentage of Amerindian ancestry was comparable between cases and controls. Morning stiffness (p < 0.0001, OR 0.05), rheumatoid factor (RF; p < 0.0001, OR 0.22), radiographic changes (p < 0.0001, OR 0.05), and higher number of criteria were associated with lower Amerindian ancestry after Bonferroni correction. Higher Amerindian ancestry correlated only with weight loss (pBonferroni < 0.0001, OR 2.85). Increased Amerindian ancestry correlated with higher doses of azathioprine (p < 0.0001, OR 163.6) and sulfasalazine (p < 0.0001, OR 48.6), and inversely with methotrexate (p = 0.001, OR 0.35), leflunomide (p = 0.001, OR 0.16), and nonsteroidal antiinflammatory drugs (pBonferroni = 0.001, OR 0.37). Only the presence of RF and weight loss were modified after confounders adjustment.Conclusion.Amerindian ancestry protects against most major clinical criteria of RA, but regarding the association of RF with increased European ancestry, age, sex, and smoking are modifiers. Ancestry also correlates with the therapeutic profiles.
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| 24. |
- Bill, Roslyn M., et al.
(author)
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Overcoming barriers to membrane protein structure determination.
- 2011
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In: Nature biotechnology. - : Springer Science and Business Media LLC. - 1546-1696 .- 1087-0156. ; 29:4, s. 335-40
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Journal article (peer-reviewed)abstract
- After decades of slow progress, the pace of research on membrane protein structures is beginning to quicken thanks to various improvements in technology, including protein engineering and microfocus X-ray diffraction. Here we review these developments and, where possible, highlight generic new approaches to solving membrane protein structures based on recent technological advances. Rational approaches to overcoming the bottlenecks in the field are urgently required as membrane proteins, which typically comprise ~30% of the proteomes of organisms, are dramatically under-represented in the structural database of the Protein Data Bank.
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| 25. |
- Dorschel, Boris, et al.
(author)
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The International Bathymetric Chart of the Southern Ocean Version 2
- 2022
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In: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 9:1
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Journal article (peer-reviewed)abstract
- The Southern Ocean surrounding Antarctica is a region that is key to a range of climatic and oceanographic processes with worldwide effects, and is characterised by high biological productivity and biodiversity. Since 2013, the International Bathymetric Chart of the Southern Ocean (IBCSO) has represented the most comprehensive compilation of bathymetry for the Southern Ocean south of 60 degrees S. Recently, the IBCSO Project has combined its efforts with the Nippon Foundation - GEBCO Seabed 2030 Project supporting the goal of mapping the world's oceans by 2030. New datasets initiated a second version of IBCSO (IBCSO v2). This version extends to 50 degrees S (covering approximately 2.4 times the area of seafloor of the previous version) including the gateways of the Antarctic Circumpolar Current and the Antarctic circumpolar frontal systems. Due to increased (multibeam) data coverage, IBCSO v2 significantly improves the overall representation of the Southern Ocean seafloor and resolves many submarine landforms in more detail. This makes IBCSO v2 the most authoritative seafloor map of the area south of 50 degrees S.
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| 28. |
- Mellor, Russell H, et al.
(author)
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Lymphatic dysfunction, not aplasia, underlies Milroy disease.
- 2010
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In: Microcirculation. - : Wiley. - 1073-9688 .- 1549-8719. ; 17:4
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Milroy disease is an inherited autosomal dominant lymphoedema caused by mutations in the gene for vascular endothelial growth factor receptor-3 (VEGFR-3, also known as FLT4). The phenotype has to date been ascribed to lymphatic aplasia. We further investigated the structural and functional defects underlying the phenotype in humans.METHODS: The skin of the swollen foot and the non-swollen forearm was examined by (i) fluorescence microlymphangiography, to quantify functional initial lymphatic density in vivo; and (ii) podoplanin and LYVE-1 immunohistochemistry of biopsies, to quantify structural lymphatic density. Leg vein function was assessed by colour Doppler duplex ultrasound.RESULTS: Milroy patients exhibited profound (86-91%) functional failure of the initial lymphatics in the foot; the forearm was unimpaired. Dermal lymphatics were present in biopsies but density was reduced by 51-61% (foot) and 26-33% (forearm). Saphenous venous reflux was present in 9/10 individuals with VEGFR3 mutations, including two carriers.CONCLUSION: We propose that VEGFR3 mutations in humans cause lymphoedema through a failure of tissue protein and fluid absorption. This is due to a profound functional failure of initial lymphatics and is not explained by microlymphatic hypoplasia alone. The superficial venous valve reflux indicates the dual role of VEGFR-3 in lymphatic and venous development.
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| 29. |
- Mellor, Russell H, et al.
(author)
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Mutations in FOXC2 in humans (lymphoedema distichiasis syndrome) cause lymphatic dysfunction on dependency.
- 2011
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In: Journal of Vascular Research. - : S. Karger AG. - 1018-1172 .- 1423-0135. ; 48:5
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Journal article (peer-reviewed)abstract
- BACKGROUND: Human lymphoedema distichiasis syndrome (LDS) results from germline mutations in transcription factor FOXC2. In a mouse model, lack of lymphatic and venous valves is observed plus abnormal smooth muscle cell recruitment to initial lymphatics. We investigated the mechanism of lymphoedema in humans with FOXC2 mutations, specifically the effect of gravitational forces on dermal lymphatic function.METHODS: We performed (1) quantitative fluorescence microlymphangiography (FML) on the skin of the forearm (non-swollen region) at heart level, and the foot (swollen region) below heart level (dependent) and then at heart level, and (2) immunohistochemical staining of microlymphatics in forearm and foot skin biopsies, using antibodies to podoplanin, LYVE-1 and smooth muscle actin.RESULTS: FML revealed a marked reduction in fluid uptake by initial lymphatics in the LDS foot during dependency, yet normal uptake (similar to controls) in the same foot at heart level and in LDS forearms. In control subjects, dependency did not impair initial lymphatic filling. Immunohistochemical microlymphatic density in forearm and foot did not differ between LDS and controls.CONCLUSIONS: FOXC2 mutations cause a functional failure of dermal initial lymphatics during gravitational stress (dependency), but not hypoplasia. The results reveal a pathophysiological mechanism contributing to swelling in LDS.
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| 33. |
- Tate, A. E., et al.
(author)
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Association and Familial Coaggregation of Type 1 Diabetes and Eating Disorders: A Register-Based Cohort Study in Denmark and Sweden
- 2021
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 44:5, s. 1143-1150
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Journal article (peer-reviewed)abstract
- OBJECTIVE To ascertain the association and coaggregation of eating disorders and childhood-onset type 1 diabetes in families. RESEARCH DESIGN AND METHODS Using population samples from national registers in Sweden (n = 2,517,277) and Demark (n = 1,825,920), we investigated the within-individual association between type 1 diabetes and eating disorders and their familial coaggregation among full siblings, half siblings, full cousins, and half cousins. On the basis of clinical diagnoses, we classified eating disorders into any eating disorder (AED), anorexia nervosa (AN) and atypical AN, and other eating disorder (OED). Associations were determined with hazard ratios (HRs) with 95% CIs from Cox regressions. RESULTS Swedish and Danish individuals with a type 1 diabetes diagnosis had a greater risk of receiving an eating disorder diagnosis (HR [95% CI] Sweden: AED 2.02 [1.80-2.27], AN 1.63 [1.36-1.96], OED 2.34 [2.07-2.63]; Denmark: AED 2.19 [1.84-2.61], AN 1.78 [1.36-2.33], OED 2.65 [2.20-3.21]). We also meta-analyzed the results: AED 2.07 (1.88-2.28), AN 1.68 (1.44-1.95), OED 2.44 (2.17-2.72). There was an increased risk of receiving an eating disorder diagnosis in full siblings in the Swedish cohort (AED 1.25 [1.07-1.46], AN 1.28 [1.04-1.57], OED 1.28 [1.07-1.52]); these results were nonsignificant in the Danish cohort. CONCLUSIONS Patients with type 1 diabetes are at a higher risk of subsequent eating disorders; however, there is conflicting support for the relationship between having a sibling with type 1 diabetes and an eating disorder diagnosis. Diabetes health care teams should be vigilant about disordered eating behaviors in children and adolescents with type 1 diabetes.
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| 34. |
- Tate, A. E., et al.
(author)
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Borderline personality disorder: associations with psychiatric disorders, somatic illnesses, trauma, and adverse behaviors
- 2022
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In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 27, s. 2514-2521
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Journal article (peer-reviewed)abstract
- In one of the largest, most comprehensive studies on borderline personality disorder (BPD) to date, this article places into context associations between this diagnosis and (1) 16 different psychiatric disorders, (2) eight somatic illnesses, and (3) six trauma and adverse behaviors, e.g., violent crime victimization and self-harm. Second, it examines the sex differences in individuals with BPD and their siblings. A total of 1,969,839 Swedish individuals were identified from national registers. Cumulative incidence with 95% confidence intervals (CI) was evaluated after 5 years of follow-up from BPD diagnosis and compared with a matched cohort. Associations were estimated as hazard ratios (HR) with 95% CIs from Cox regression. 12,175 individuals were diagnosed with BPD (85.3% female). Individuals diagnosed with BPD had higher cumulative incidences and HRs for nearly all analyzed indicators, especially psychiatric disorders. Anxiety disorders were most common (cumulative incidence 95% CI 33.13% [31.48-34.73]). Other notable findings from Cox regressions include psychotic disorders (HR 95% CI 24.48 [23.14-25.90]), epilepsy (3.38 [3.08-3.70]), violent crime victimization (7.65 [7.25-8.06]), and self-harm (17.72 [17.27-18.19]). HRs in males and females with BPD had overlapping CIs for nearly all indicators. This indicates that a BPD diagnosis is a marker of vulnerability for negative events and poor physical and mental health similarly for both males and females. Having a sibling with BPD was associated with an increased risk for psychiatric disorders, trauma, and adverse behaviors but not somatic disorders. Clinical implications include the need for increased support for patients with BPD navigating the health care system.
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| 35. |
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| 36. |
- Vlaeyen, Johan W. S., et al.
(author)
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From Boulder to Stockholm in 70 Years : Single Case Experimental Designs in Clinical Research
- 2020
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In: The Psychological Record. - : Springer. - 0033-2933 .- 2163-3452. ; 70:4, s. 659-670
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Journal article (peer-reviewed)abstract
- With the objective of increasing the magnitude of treatment effects in behavioral health, there is steadily growing interest in tailoring assessments and interventions to better match individual needs. This aligns with the central idea that behavior can be adequately understood by considering the unique characteristics of the individual and context. Thus, data collected at an individual level provides critical evidence that can be used to inform health care decisions, improve treatment, or refine theories. Yet, the majority of research in behavioral health is based on group-level analyses. Recent developments in the field of single-case experimental design (SCED) has provided new opportunities to utilize individual data. The present article provides a state-of-the art overview regarding key aspects of SCED, including a historical background to why and how SCED emerged, declined, and recently reemerged as well as methodological aspects such as design issues, challenges related to reliability and validity of repeated observations, innovations in visual and statistical analyses of individual data, strategies to deal with missing values, methodology to examine effect size, and approaches to summarize data from a large number of SCEDs using multilevel models and meta-analyses of replication data. Finally, the article discusses key concerns and actions needed to move the field forward.
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| 37. |
- Yeung, A T Y, et al.
(author)
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Conditional-ready mouse embryonic stem cell derived macrophages enable the study of essential genes in macrophage function
- 2015
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 5
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Journal article (peer-reviewed)abstract
- The ability to differentiate genetically modified mouse embryonic stem (ES) cells into functional macrophages provides a potentially attractive resource to study host-pathogen interactions without the need for animal experimentation. This is particularly useful in instances where the gene of interest is essential and a knockout mouse is not available. Here we differentiated mouse ES cells into macrophages in vitro and showed, through a combination of flow cytometry, microscopic imaging and RNA-Seq, that ES cell-derived macrophages responded to S. Typhimurium, in a comparable manner to mouse bone marrow derived macrophages. We constructed a homozygous mutant mouse ES cell line in the Traf2 gene that is known to play a role in tumour necrosis factor-α signalling but has not been studied for its role in infections or response to Toll-like receptor agonists. Interestingly, traf2-deficient macrophages produced reduced levels of inflammatory cytokines in response to lipopolysaccharide (LPS) or flagellin stimulation and exhibited increased susceptibility to S. Typhimurium infection.
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