| 1. |
- Abazov, V. M., et al.
(författare)
-
The upgraded DO detector
- 2006
-
Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 565:2, s. 463-537
-
Tidskriftsartikel (refereegranskat)abstract
- The DO experiment enjoyed a very successful data-collection run at the Fermilab Tevatron collider between 1992 and 1996. Since then, the detector has been upgraded to take advantage of improvements to the Tevatron and to enhance its physics capabilities. We describe the new elements of the detector, including the silicon microstrip tracker, central fiber tracker, solenoidal magnet, preshower detectors, forward muon detector, and forward proton detector. The uranium/liquid -argon calorimeters and central muon detector, remaining from Run 1, are discussed briefly. We also present the associated electronics, triggering, and data acquisition systems, along with the design and implementation of software specific to DO.
|
|
| 2. |
- Locke, Adam E, et al.
(författare)
-
Genetic studies of body mass index yield new insights for obesity biology.
- 2015
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
-
Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
|
|
| 3. |
- Clark, DW, et al.
(författare)
-
Associations of autozygosity with a broad range of human phenotypes
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4957-
-
Tidskriftsartikel (refereegranskat)abstract
- In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Polme, S., et al.
(författare)
-
FungalTraits: a user-friendly traits database of fungi and fungus-like stramenopiles
- 2020
-
Ingår i: Fungal Diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 105:1, s. 1-16
-
Tidskriftsartikel (refereegranskat)abstract
- The cryptic lifestyle of most fungi necessitates molecular identification of the guild in environmental studies. Over the past decades, rapid development and affordability of molecular tools have tremendously improved insights of the fungal diversity in all ecosystems and habitats. Yet, in spite of the progress of molecular methods, knowledge about functional properties of the fungal taxa is vague and interpretation of environmental studies in an ecologically meaningful manner remains challenging. In order to facilitate functional assignments and ecological interpretation of environmental studies we introduce a user friendly traits and character database FungalTraits operating at genus and species hypothesis levels. Combining the information from previous efforts such as FUNGuild and Fun(Fun) together with involvement of expert knowledge, we reannotated 10,210 and 151 fungal and Stramenopila genera, respectively. This resulted in a stand-alone spreadsheet dataset covering 17 lifestyle related traits of fungal and Stramenopila genera, designed for rapid functional assignments of environmental studies. In order to assign the trait states to fungal species hypotheses, the scientific community of experts manually categorised and assigned available trait information to 697,413 fungal ITS sequences. On the basis of those sequences we were able to summarise trait and host information into 92,623 fungal species hypotheses at 1% dissimilarity threshold.
|
|
| 9. |
- Asselbergs, Folkert W., et al.
(författare)
-
Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci
- 2012
-
Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 91:5, s. 823-838
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering similar to 2,000 candidate genes. SNP-lipid associations were replicated either in a cohort comprising an additional 24,736 samples or within the Global Lipid Genetic Consortium. We identified four, six, ten, and four unreported SNPs in established lipid genes for HDL-C, LDL-C, TC, and TGs, respectively. We also identified several lipid-related SNPs in previously unreported genes: DGAT2, HCAR2, GPIHBP1, PPARG, and FTO for HDL-C; SOCS3, APOH, SPTY2D1, BRCA2, and VLDLR for LDL-C; SOCS3, UGT1A1, BRCA2, UBE3B, FCGR2A, CHUK, and INSIG2 for TC; and SERPINF2, C4B, GCK, GATA4, INSR, and LPAL2 for TGs. The proportion of explained phenotypic variance in the subset of studies providing individual-level data was 9.9% for HDL-C, 9.5% for LDL-C, 10.3% for TC, and 8.0% for TGs. This large meta-analysis of lipid phenotypes with the use of a dense gene-centric approach identified multiple SNPs not previously described in established lipid genes and several previously unknown loci. The explained phenotypic variance from this approach was comparable to that from a meta-analysis of GWAS data, suggesting that a focused genotyping approach can further increase the understanding of heritability of plasma lipids.
|
|
| 10. |
- Ganesh, Santhi K., et al.
(författare)
-
Loci influencing blood pressure identified using a cardiovascular gene-centric array
- 2013
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 22:8, s. 1663-1678
-
Tidskriftsartikel (refereegranskat)abstract
- Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped 50 000 single-nucleotide polymorphisms (SNPs) that capture variation in 2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P 2.4 10(6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.
|
|
| 11. |
- Joshi, Peter K, et al.
(författare)
-
Directional dominance on stature and cognition in diverse human populations
- 2015
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
-
Tidskriftsartikel (refereegranskat)abstract
- Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
|
|
| 12. |
- Postmus, I., et al.
(författare)
-
Meta-analysis of genome-wide association studies of HDL cholesterol response to statins
- 2016
-
Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 53:12, s. 835-45
-
Tidskriftsartikel (refereegranskat)abstract
- Background In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Interindividual variation in HDL-C response to statins may be partially explained by genetic variation. Methods and results We performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p<1x10(-4) from the 16 769 statin-treated participants in the first analysis stage were followed up in an independent group of 10 951 statin-treated individuals, providing a total sample size of 27 720 individuals. The only associations of genome-wide significance (p<5x10(-8)) were between minor alleles at the CETP locus and greater HDL-C response to statin treatment. Conclusions Based on results from this study that included a relatively large sample size, we suggest that CETP may be the only detectable locus with common genetic variants that influence HDL-C response to statins substantially in individuals of European descent. Although CETP is known to be associated with HDL-C, we provide evidence that this pharmacogenetic effect is independent of its association with baseline HDL-C levels.
|
|
| 13. |
- Tragante, Vinicius, et al.
(författare)
-
Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci.
- 2014
-
Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:3, s. 349-360
-
Tidskriftsartikel (refereegranskat)abstract
- Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
- Postmus, Iris, et al.
(författare)
-
Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.
- 2014
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
- Smith, Daniel G. A., et al.
(författare)
-
Quantum Chemistry Common Driver and Databases (QCDB) and Quantum Chemistry Engine (QCEngine) : Automation and interoperability among computational chemistry programs
- 2021
-
Ingår i: Journal of Chemical Physics. - : American Institute of Physics (AIP). - 0021-9606 .- 1089-7690. ; 155:20
-
Tidskriftsartikel (refereegranskat)abstract
- Community efforts in the computational molecular sciences (CMS) are evolving toward modular, open, and interoperable interfaces that work with existing community codes to provide more functionality and composability than could be achieved with a single program. The Quantum Chemistry Common Driver and Databases (QCDB) project provides such capability through an application programming interface (API) that facilitates interoperability across multiple quantum chemistry software packages. In tandem with the Molecular Sciences Software Institute and their Quantum Chemistry Archive ecosystem, the unique functionalities of several CMS programs are integrated, including CFOUR, GAMESS, NWChem, OpenMM, Psi4, Qcore, TeraChem, and Turbomole, to provide common computational functions, i.e., energy, gradient, and Hessian computations as well as molecular properties such as atomic charges and vibrational frequency analysis. Both standard users and power users benefit from adopting these APIs as they lower the language barrier of input styles and enable a standard layout of variables and data. These designs allow end-to-end interoperable programming of complex computations and provide best practices options by default.
|
|
| 22. |
|
|
| 23. |
- de Bakker, Paul I. W., et al.
(författare)
-
Transferability of tag SNPs in genetic association studies in multiple populations
- 2006
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 38:11, s. 1298-1303
-
Tidskriftsartikel (refereegranskat)abstract
- A general question for linkage disequilibrium-based association studies is how power to detect an association is compromised when tag SNPs are chosen from data in one population sample and then deployed in another sample. Specifically, it is important to know how well tags picked from the HapMap DNA samples capture the variation in other samples. To address this, we collected dense data uniformly across the four HapMap population samples and eleven other population samples. We picked tag SNPs using genotype data we collected in the HapMap samples and then evaluated the effective coverage of these tags in comparison to the entire set of common variants observed in the other samples. We simulated case-control association studies in the non-HapMap samples under a disease model of modest risk, and we observed little loss in power. These results demonstrate that the HapMap DNA samples can be used to select tags for genome-wide association studies in many samples around the world.
|
|
| 24. |
- Forsberg, Lars A., et al.
(författare)
-
Age-related somatic structural changes in the nuclear genome of human blood cells
- 2012
-
Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 90:2, s. 217-228
-
Tidskriftsartikel (refereegranskat)abstract
- Structural variations are among the most frequent interindividual genetic differences in the human genome. The frequency and distribution of de novo somatic structural variants in normal cells is, however, poorly explored. Using age-stratified cohorts of 318 monozygotic (MZ) twins and 296 single-born subjects, we describe age-related accumulation of copy-number variation in the nuclear genomes in vivo and frequency changes for both megabase- and kilobase-range variants. Megabase-range aberrations were found in 3.4% (9 of 264) of subjects ≥60 years old; these subjects included 78 MZ twin pairs and 108 single-born individuals. No such findings were observed in 81 MZ pairs or 180 single-born subjects who were ≤55 years old. Recurrent region- and gene-specific mutations, mostly deletions, were observed. Longitudinal analyses of 43 subjects whose data were collected 7-19 years apart suggest considerable variation in the rate of accumulation of clones carrying structural changes. Furthermore, the longitudinal analysis of individuals with structural aberrations suggests that there is a natural self-removal of aberrant cell clones from peripheral blood. In three healthy subjects, we detected somatic aberrations characteristic of patients with myelodysplastic syndrome. The recurrent rearrangements uncovered here are candidates for common age-related defects in human blood cells. We anticipate that extension of these results will allow determination of the genetic age of different somatic-cell lineages and estimation of possible individual differences between genetic and chronological age. Our work might also help to explain the cause of an age-related reduction in the number of cell clones in the blood; such a reduction is one of the hallmarks of immunosenescence.
|
|
| 25. |
- Kersten, CM, et al.
(författare)
-
The Management of Asymptomatic Congenital Pulmonary Airway Malformation: Results of a European Delphi Survey
- 2022
-
Ingår i: Children (Basel, Switzerland). - : MDPI AG. - 2227-9067. ; 9:8
-
Tidskriftsartikel (refereegranskat)abstract
- Consensus on the optimal management of asymptomatic congenital pulmonary airway malformation (CPAM) is lacking, and comparison between studies remains difficult due to a large variety in outcome measures. We aimed to define a core outcome set (COS) for pediatric patients with an asymptomatic CPAM. An online, three-round Delphi survey was conducted in two stakeholder groups of specialized caregivers (surgeons and non-surgeons) in various European centers. Proposed outcome parameters were scored according to level of importance, and the final COS was established through consensus. A total of 55 participants (33 surgeons, 22 non-surgeons) from 28 centers in 13 European countries completed the three rounds and rated 43 outcome parameters. The final COS comprises seven outcome parameters: respiratory insufficiency, surgical complications, mass effect/mediastinal shift (at three time-points) and multifocal disease (at two time-points). The seven outcome parameters included in the final COS reflect the diversity in priorities among this large group of European participants. However, we recommend the incorporation of these outcome parameters in the design of future studies, as they describe measurable and validated outcomes as well as the accepted age at measurement.
|
|
| 26. |
- Stinesen-Kollberg, Karin, et al.
(författare)
-
Chronic Stress in Vocational and Intimate Partner Domains as Predictors of Depressive Symptoms After Breast Cancer Diagnosis.
- 2019
-
Ingår i: Annals of behavioral medicine : a publication of the Society of Behavioral Medicine. - : Oxford University Press (OUP). - 1532-4796. ; 53:4, s. 333-344
-
Tidskriftsartikel (refereegranskat)abstract
- After cancer diagnosis, depressive symptoms are elevated on average and decline over time, but substantial variability is apparent. Few studies have examined to what extent chronic stress in distinct life domains affects depressive symptoms.Chronic stress in vocational and intimate partner life domains, and their interaction, were tested as predictors of depressive symptoms after breast cancer diagnosis.Women (N = 460) completed validated interviews regarding chronic stress in specific life domains shortly after diagnosis and a measure of depressive symptoms every 6 weeks for 6 months.In latent growth curve modeling analyses, greater chronic stress in work (b = 2.90; p < .001) and intimate partner domains (b = 1.38, p = .02) was associated with higher depressive symptoms at study entry (intercept), and greater work stress predicted faster recovery from depressive symptoms over time (b = -0.10; p = .01). The two domains of chronic stress also interacted significantly on depressive symptoms at study entry (b = -1.54; p < .02) and over time (b = 0.14; p < .001). Greater work stress was associated with higher depressive symptoms at study entry regardless of intimate partner stress, but greater intimate partner stress was associated with higher depressive symptoms when work stress was low. The decline over 6 months in initially elevated depressive symptoms predicted by high work stress was significantly steeper when intimate partner stress was low.Targeting interventions to recently diagnosed breast cancer patients living with chronically stressful vocational and intimate partner life circumstances could be worthwhile.
|
|
| 27. |
- Surendran, Praveen, et al.
(författare)
-
Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension
- 2016
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:10, s. 1151-1161
-
Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used -1/4155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.
|
|
| 28. |
|
|
| 29. |
- Boeskorov, G G, et al.
(författare)
-
The Preliminary Analysis of Cave Lion Cubs Panthera spelaea (Goldfuss, 1810) from the Permafrost of Siberia
- 2021
-
Ingår i: Quaternary. - : MDPI AG. - 2571-550X. ; 4:3
-
Tidskriftsartikel (refereegranskat)abstract
- A preliminary description is presented of the well-preserved frozen mummies of two cubs of the extinct cave lion Panthera spelaea (finds of 2017–2018, Semyuelyakh River, Yakutia, eastern Siberia, Russia). The fossil lion cubs were found in close proximity, but they do not belong to the same litter, since their radiocarbon ages differ: the female (named ‘Sparta’) was dated to 27,962 ± 109 uncal years BP, and the male (named ‘Boris’) was dated to 43,448 ± 389 uncal years BP. The lion cubs have similar individual ages, 1–2 months. The general tone of the colour of the fur coat of Sparta is greyish to light brown, whereas, in Boris, the fur is generally lighter, greyish yellowish. It is, therefore, possible that light colouration prevailed with age in cave lions and was adaptive for northern snow-covered landscapes. The article discusses the results of computed tomography of cubs of the cave lion, the possible reasons for their death, and the peculiarities of their existence in the Siberian Arctic.
|
|
| 30. |
- Dussex, Nicolas, et al.
(författare)
-
Biomolecular analyses reveal the age, sex and species identity of a near-intact Pleistocene bird carcass
- 2020
-
Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
-
Tidskriftsartikel (refereegranskat)abstract
- Ancient remains found in permafrost represent a rare opportunity to study past ecosystems. Here, we present an exceptionally well-preserved ancient bird carcass found in the Siberian permafrost, along with a radiocarbon date and a reconstruction of its complete mitochondrial genome. The carcass was radiocarbon dated to approximately 44-49 ka BP, and was genetically identified as a female horned lark. This is a species that usually inhabits open habitat, such as the steppe environment that existed in Siberia at the time. This near-intact carcass highlights the potential of permafrost remains for evolutionary studies that combine both morphology and ancient nucleic acids. Nicolas Dussex et al. identify a 44,000-49,000 year old bird found in Siberian permafrost as a female horned lark using ancient DNA. This exceptionally well-preserved specimen illustrates the potential contribution to science of permafrost deposits, such as the study of ecology and evolution of ancient ecosystems, calibration of molecular clocks, and furthering our understanding of processes such as biological regulation and gene expression in relation to climate change.
|
|
| 31. |
- Eisfeldt, Andrea L., et al.
(författare)
-
The Deposit Business at Large vs. Small Banks
- 2023
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The deposit business differs at large versus small banks. We provide a parsimonious model and extensive empirical evidence supporting the idea that much of the variation in deposit-pricing behavior between large and small banks reflects differences in "preferences and technologies." Large banks offer superior liquidity services but lower deposit rates, and locate where customers value their services. In addition to receiving a lower level of deposit rates on average, customers of large banks exhibit lower demand elasticities with respect to deposit rate spreads. As a result, despite the fact that the locations of large-bank branches have demographics typically associated with greater financial sophistication, large-bank customers earn lower average deposit rates. Our explanation for deposit pricing behavior challenges the idea that deposit pricing is mainly driven by pricing power derived from the large observed degree of concentration in the banking industry.
|
|
| 32. |
- Eisfeldt, Andrea L., et al.
(författare)
-
The Deposit Business at Large vs. Small Banks
- 2023
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We provide a parsimonious model and extensive empirical evidence supporting the idea that much of the variation in deposit-pricing behavior across large vs. small banks reflects differences in ``preferences and technologies''. Large banks offer superior liquidity services, but lower deposit rates, and locate where customers value their services. In addition to receiving a lower level of deposit rates on average, customers of large banks exhibit lower demand elasticities with respect to deposit rate spreads. As a result, despite the fact that the locations of large-bank branches have demographics typically associated with greater financial sophistication, large-bank customers earn lower average deposit rates. Our explanation for deposit pricing behavior challenges the idea that deposit pricing is mainly driven by pricing power derived from the large observed degree of concentration in the banking industry.
|
|
| 33. |
- Evangelou, Evangelos, et al.
(författare)
-
Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
- 2018
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
-
Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
|
|
| 34. |
- James, Samuel W., et al.
(författare)
-
A neotype for Pontoscolex corethrurus (Muller, 1857) (Clitellata)
- 2019
-
Ingår i: Zootaxa. - Aukland, New Zealand : MAGNOLIA PRESS. - 1175-5326 .- 1175-5334. ; 4545:1, s. 124-132
-
Tidskriftsartikel (refereegranskat)abstract
- Following many decades of work on the taxonomy, biology and ecology of the globally-distributed tropical earthworm Pontoscolex corethrurus (Muller, 1857), morphological and molecular data have shown that the stability and effectiveness of nomenclature depends on the designation of a neotype from the type locality. We do that, with all the required justifications, and provide sufficient information to permit the correct identification of this species.
|
|
| 35. |
- Kappos, Ludwig, et al.
(författare)
-
Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study
- 2018
-
Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 391, s. 1263-1273
-
Tidskriftsartikel (refereegranskat)abstract
- © 2018 Elsevier Ltd Background: No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor 1,5 modulator, on disability progression in patients with SPMS. Methods: This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatme nt arms, patients (age 18–60 years) with SPMS and an Expanded Disability Status Scale score of 3·0–6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. Findings: 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65–0·95; relative risk reduction 21%; p=0·013). Adverse events occurred in 975 (89%) of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving placebo; serious adverse events were reported for 197 (18%) patients in the siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia, increased liver transaminase concentration, bradycardia and bradyarrhythmia at treatment initiation, macular oedema, hypertension, varicella zoster reactivation, and convulsions occurred more frequently with siponimod than with placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies of infections, malignancies, and fatalities did not differ between groups. Interpretation: Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS. Funding: Novartis Pharma AG.
|
|
| 36. |
|
|
| 37. |
|
|
| 38. |
- Lord, Edana, et al.
(författare)
-
Pre-extinction Demographic Stability and Genomic Signatures of Adaptation in the Woolly Rhinoceros
- 2020
-
Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 30:19
-
Tidskriftsartikel (refereegranskat)abstract
- Ancient DNA has significantly improved our understanding of the evolution and population history of extinct megafauna. However, few studies have used complete ancient genomes to examine species responses to climate change prior to extinction. The woolly rhinoceros (Coelodonta antiquitatis) was a cold-adapted megaherbivore widely distributed across northern Eurasia during the Late Pleistocene and became extinct approximately 14 thousand years before present (ka BP). While humans and climate change have been proposed as potential causes of extinction [1-3], knowledge is limited on how the woolly rhinoceros was impacted by human arrival and climatic fluctuations [2]. Here, we use one complete nuclear genome and 14 mitogenomes to investigate the demographic history of woolly rhinoceros leading up to its extinction. Unlike other northern megafauna, the effective population size of woolly rhinoceros likely increased at 29.7 ka BP and subsequently remained stable until close to the species’ extinction. Analysis of the nuclear genome from a similar to 18.5-ka-old specimen did not indicate any increased inbreeding or reduced genetic diversity, suggesting that the population size remained steady for more than 13 ka following the arrival of humans [4]. The population contraction leading to extinction of the woolly rhinoceros may have thus been sudden and mostly driven by rapid warming in the Bolling-Allerod interstadial. Furthermore, we identify woolly rhinoceros-specific adaptations to arctic climate, similar to those of the woolly mammoth. This study highlights how species respond differently to climatic fluctuations and further illustrates the potential of palaeogenomics to study the evolutionary history of extinct species.
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
|
|
| 43. |
- Reid, G., et al.
(författare)
-
How do probiotics and prebiotics function at distant sites?
- 2017
-
Ingår i: Beneficial Microbes. - : WAGENINGEN ACADEMIC PUBLISHERS. - 1876-2883 .- 1876-2891. ; 8:4, s. 521-533
-
Tidskriftsartikel (refereegranskat)abstract
- The realisation that microbes regarded as beneficial to the host can impart effects at sites distant from their habitat, has raised many possibilities for treatment of diseases. The objective of a workshop hosted in Turku, Finland, by the International Scientific Association for Probiotics and Prebiotics, was to assess the evidence for these effects and the extent to which early life microbiome programming influences how the gut microbiota communicates with distant sites. In addition, we examined how probiotics and prebiotics might affect the skin, airways, heart, brain and metabolism. The growing levels of scientific and clinical evidence showing how microbes influence the physiology of many body sites, leads us to call for more funding to advance a potentially exciting avenue for novel therapies for many chronic diseases.
|
|
| 44. |
|
|
| 45. |
- Schinazi, Raymond F., et al.
(författare)
-
Selection and Characterization of HIV-1 with a Novel S68 Deletion in Reverse Transcriptase
- 2011
-
Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 55:5, s. 2054-2060
-
Tidskriftsartikel (refereegranskat)abstract
- Resistance to human immunodeficiency virus type 1 (HIV-1) represents a significant problem in the design of novel therapeutics and the management of treatment regimens in infected persons. Resistance profiles can be elucidated by defining modifications to the viral genome conferred upon exposure to novel nucleoside reverse transcriptase (RT) inhibitors (NRTI). In vitro testing of HIV-1(LAI)-infected primary human lymphocytes treated with beta-D-2',3'-dideoxy-2',3'-didehydro-5-fluorocytidine (DFC; Dexelvucitabine; Reverset) produced a novel deletion of AGT at codon 68 (S68 Delta) alone and in combination with K65R that differentially affects drug response. Dual-approach clone techniques utilizing TOPO cloning and pyrosequencing confirmed the novel S68 Delta in the HIV-1 genome. The S68 Delta HIV-1 RT was phenotyped against various antiviral agents in a heteropolymeric DNA polymerase assay and in human lymphocytes. Drug susceptibility results indicate that the S68 Delta displayed a 10- to 30-fold increase in resistance to DFC, lamivudine, emtricitabine, tenofovir, abacavir, and amdoxovir and modest resistance to stavudine, beta-D-2',3'-oxa-5-fluorocytidine, or 9-(beta-D-1,3-dioxolan-4-yl) guanine and remained susceptible to 3'-azido-3'-deoxythymidine, 2',3'-dideoxyinosine (ddI), 1-(beta-D-dioxolane) thymine (DOT) and lopinavir. Modeling revealed a central role for S68 in affecting conformation of the beta 3-beta 4 finger region and provides a rational for the selective resistance. These data indicate that the novel S68 Delta is a previously unrecognized deletion that may represent an important factor in NRTI multidrug resistance treatment strategies.
|
|
| 46. |
- Stanton, E. B., et al.
(författare)
-
Cardiac troponin I, a possible predictor of survival in patients with stable congestive heart failure
- 2005
-
Ingår i: The Canadian journal of cardiology. - 0828-282X. ; 21:1, s. 39-43
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cardiac troponin I (cTnI) has been validated as a sensitive and specific marker of myocyte damage, and is elevated in some patients with congestive heart failure. OBJECTIVE: To assess the relationship between elevated levels of cTnI and survival in stable patients with congestive heart failure. PATIENTS AND METHODS: It was assessed whether detectable serial levels of cTnI were associated with mortality in 211 patients with stable, severe heart failure at entry and one month into the Prospective Randomized Flosequinan Longevity Evaluation (PROFILE) study. Of these patients, 66 also had measurements taken at 12 months. RESULTS: Patients were New York Heart Association (NYHA) class III (n=197) or IV (n=14), with a baseline left ventricular ejection fraction of 22+/-7% (range 8% to 35%). Patients with a detectable level of cTnI at one month had an increased mortality (OR 2.608 [95% CI 1.061 to 6.409]; P=0.037). The association between mortality and detectable cTnI levels at baseline or 12 months did not reach statistical significance. Patients with a cTnI level that rose or remained elevated between baseline and one month had a higher mortality rate (50%) than those in whom the cTnI level fell (9%) between baseline and one month (P=0.025). In a multivariate model of survival that included sex, treatment, age, left ventricular ejection fraction, NYHA class and creatinine, only detectable levels of cTnI at one month were associated with survival (P=0.037). CONCLUSIONS: cTnI is released in stable, chronic heart failure and is associated with a poor prognosis, independent of other important risk factors. The risk is particularly elevated when detectable cTnI levels rise or remain elevated over time.
|
|
| 47. |
- Urban, Lara, et al.
(författare)
-
Real-time genomics for One Health
- 2023
-
Ingår i: Molecular Systems Biology. - 1744-4292. ; 19:8
-
Forskningsöversikt (refereegranskat)abstract
- The ongoing degradation of natural systems and other environmental changes has put our society at a crossroad with respect to our future relationship with our planet. While the concept of One Health describes how human health is inextricably linked with environmental health, many of these complex interdependencies are still not well-understood. Here, we describe how the advent of real-time genomic analyses can benefit One Health and how it can enable timely, in-depth ecosystem health assessments. We introduce nanopore sequencing as the only disruptive technology that currently allows for real-time genomic analyses and that is already being used worldwide to improve the accessibility and versatility of genomic sequencing. We showcase real-time genomic studies on zoonotic disease, food security, environmental microbiome, emerging pathogens, and their antimicrobial resistances, and on environmental health itself – from genomic resource creation for wildlife conservation to the monitoring of biodiversity, invasive species, and wildlife trafficking. We stress why equitable access to real-time genomics in the context of One Health will be paramount and discuss related practical, legal, and ethical limitations.
|
|
