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| 2. |
- Fages, A., et al.
(författare)
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Tracking Five Millennia of Horse Management with Extensive Ancient Genome Time Series
- 2019
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Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 177:6
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Tidskriftsartikel (refereegranskat)abstract
- Horse domestication revolutionized warfare and accelerated travel, trade, and the geographic expansion of languages. Here, we present the largest DNA time series for a non-human organism to date, including genome-scale data from 149 ancient animals and 129 ancient genomes (>= 1-fold coverage), 87 of which are new. This extensive dataset allows us to assess the modem legacy of past equestrian civilisations. We find that two extinct horse lineages existed during early domestication, one at the far western (Iberia) and the other at the far eastern range (Siberia) of Eurasia. None of these contributed significantly to modern diversity. We show that the influence of Persian-related horse lineages increased following the Islamic conquests in Europe and Asia. Multiple alleles associated with elite-racing, including at the MSTN "speed gene," only rose in popularity within the last millennium. Finally, the development of modem breeding impacted genetic diversity more dramatically than the previous millennia of human management.
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| 3. |
- Bogota-Angel, G., et al.
(författare)
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Climate and geological change as drivers of Mauritiinae palm biogeography
- 2021
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Ingår i: Journal of Biogeography. - : Wiley. - 0305-0270 .- 1365-2699. ; 48:5, s. 1001-1022
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Tidskriftsartikel (refereegranskat)abstract
- Aim Forest composition and distribution are determined by a myriad of factors, including climate. As models of tropical rain forest, palms are often used as indicator taxa, particularly the Mauritiinae. We question, what characterizes the Mauritiinae pollen in the global fossil record? And when did the Mauritiinae become endemic to South America? Location Global tropics. Taxon Mauritiinae palms (Arecaceae: Lepidocaryeae). Methods Pollen trait data from extinct and extant Mauritiinae pollen were generated from light-, scanning-, and transmission electron microscopy. Statistical morphometric analysis was used to define species and their relationships to other Mauritiinae. We also compiled a comprehensive pollen database for extinct and extant Mauritiinae and mapped their global geographical distribution from Late Cretaceous to present, using GBIF and fossil data. Results Our morphometric analysis identified 18 species (11 extinct and seven extant), all exhibiting exine indentations, a synapomorphy of the subtribe. The fossil taxa and early divergent extant Lepidocaryum are all monosulcate, whereas the extant Mauritia and Mauritiella species are all monoulcerate. Paleobiogeographical maps of fossil Mauritiinae pollen occurrences suggest the taxon originated in equatorial Africa during the Cretaceous, and expanded their range to South America, and to India in the Paleocene. Range retraction started in the early Eocene with extirpation from India, and reduction in diversity in Africa culminating at the Eocene-Oligocene Transition (EOT). In contrast, in South America, the distribution is maintained, and since the Neogene Mauritiinae palms are mostly restricted to swampy, lowland habitats. Main conclusions Morphometric analysis shows that since their origin Mauritiinae pollen are relatively species poor, and Mauritiidites resembles Lepidocaryum. We also conclude that the biogeographical history of the Mauriitinae and, by extension, tropical forests was strongly affected by global climatic cooling events. In particular, the climate change at the EOT was a fundamental determinant of current tropical forest distribution.
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| 4. |
- Hetland, M. L., et al.
(författare)
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Active conventional treatment and three different biological treatments in early rheumatoid arthritis: phase IV investigator initiated, randomised, observer blinded clinical trial
- 2020
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Ingår i: Bmj-British Medical Journal. - : BMJ. - 1756-1833. ; 371
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To evaluate and compare benefits and harms of three biological treatments with different modes of action versus active conventional treatment in patients with early rheumatoid arthritis. DESIGN Investigator initiated, randomised, open label, blinded assessor, multiarm, phase IV study. SETTING Twenty nine rheumatology departments in Sweden, Denmark, Norway, Finland, the Netherlands, and Iceland between 2012 and 2018. PARTICIPANTS Patients aged 18 years and older with treatment naive rheumatoid arthritis, symptom duration less than 24 months, moderate to severe disease activity, and rheumatoid factor or anti-citrullinated protein antibody positivity, or increased C reactive protein. INTERVENTIONS Randomised 1:1:1:1, stratified by country, sex, and anti-citrullinated protein antibody status. All participants started methotrexate combined with (a) active conventional treatment (either prednisolone tapered to 5 mg/day, or sulfasalazine combined with hydroxychloroquine and intraarticular corticosteroids), (b) certolizumab pegol, (c) abatacept, or (d) tocilizumab. MAIN OUTCOME MEASURES The primary outcome was adjusted clinical disease activity index remission (CDAI <= 2.8) at 24 weeks with active conventional treatment as the reference. Key secondary outcomes and analyses included CDAI remission at 12 weeks and over time, other remission criteria, a non-inferiority analysis, and harms. RESULTS 812 patients underwent randomisation. The mean age was 54.3 years (standard deviation 14.7) and 68.8% were women. Baseline disease activity score of 28 joints was 5.0 (standard deviation 1.1). Adjusted 24 week CDAI remission rates were 42.7% (95% confidence interval 36.1% to 49.3%) for active conventional treatment, 46.5% (39.9% to 53.1%) for certolizumab pegol, 52.0% (45.5% to 58.6%) for abatacept, and 42.1% (35.3% to 48.8%) for tocilizumab. Corresponding absolute differences were 3.9% (95% confidence interval -5.5% to 13.2%) for certolizumab pegol, 9.4% (0.1% to 18.7%) for abatacept, and -0.6% (-10.1% to 8.9%) for tocilizumab. Key secondary outcomes showed no major differences among the four treatments. Differences in CDAI remission rates for active conventional treatment versus certolizumab pegol and tocilizumab, but not abatacept, remained within the prespecified non-inferiority margin of 15% (per protocol population). The total number of serious adverse events was 13 (percentage of patients who experienced at least one event 5.6%) for active conventional treatment, 20 (8.4%) for certolizumab pegol, 10 (4.9%) for abatacept, and 10 (4.9%) for tocilizumab. Eleven patients treated with abatacept stopped treatment early compared with 20-23 patients in the other arms. CONCLUSIONS All four treatments achieved high remission rates. Higher CDAI remission rate was observed for abatacept versus active conventional treatment, but not for certolizumab pegol or tocilizumab versus active conventional treatment. Other remission rates were similar across treatments. Non-inferiority analysis indicated that active conventional treatment was non-inferior to certolizumab pegol and tocilizumab, but not to abatacept. The results highlight the efficacy and safety of active conventional treatment based on methotrexate combined with corticosteroids, with nominally better results for abatacept, in treatment naive early rheumatoid arthritis.
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| 5. |
- Barth, Julia M.I., et al.
(författare)
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Genome architecture enables local adaptation of Atlantic cod despite high connectivity
- 2017
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Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 26:17, s. 4452-4466
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Tidskriftsartikel (refereegranskat)abstract
- Adaptation to local conditions is a fundamental process in evolution; however, mechanisms maintaining local adaptation despite high gene flow are still poorly understood. Marine ecosystems provide a wide array of diverse habitats that frequently promote ecological adaptation even in species characterized by strong levels of gene flow. As one example, populations of the marine fish Atlantic cod (Gadus morhua) are highly connected due to immense dispersal capabilities but nevertheless show local adaptation in several key traits. By combining population genomic analyses based on 12K single nucleotide polymorphisms with larval dispersal patterns inferred using a biophysical ocean model, we show that Atlantic cod individuals residing in sheltered estuarine habitats of Scandinavian fjords mainly belong to offshore oceanic populations with considerable connectivity between these diverse ecosystems. Nevertheless, we also find evidence for discrete fjord populations that are genetically differentiated from offshore populations, indicative of local adaptation, the degree of which appears to be influenced by connectivity. Analyses of the genomic architecture reveal a significant overrepresentation of a large ~5 Mb chromosomal rearrangement in fjord cod, previously proposed to comprise genes critical for the survival at low salinities. This suggests that despite considerable connectivity with offshore populations, local adaptation to fjord environments may be enabled by suppression of recombination in the rearranged region. Our study provides new insights into the potential of local adaptation in high gene flow species within fine geographical scales and highlights the importance of genome architecture in analyses of ecological adaptation.
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| 6. |
- Savage, R. L., et al.
(författare)
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Severe muscle symptoms with lipid-lowering agents may be confused with neurogenic claudication associated with spinal canal stenosis
- 2012
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Ingår i: International Journal of Risk and Safety in Medicine. - 0924-6479 .- 1878-6847. ; 24:4, s. 215-219
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Tidskriftsartikel (refereegranskat)abstract
- Background: Screening of the WHO global individual case safety report database (VigiBase) has recently identified case reports with HMG CoA reductase inhibitors and muscle symptoms co-reported with spinal stenosis. In some reports spinal stenosis appears to have been listed as a coincidental finding. Objective: To assess reports with sufficient information to ascertain if they suggested that there may have been diagnostic confusion between muscle symptoms attributable to HMG CoA reductase inhibitors with or without ezetimibe and symptoms of spinal stenosis. Method: Reports were examined for patient demographics, past history, clinical and investigational findings, co-prescribed medicines and outcomes. Results: Three case histories recorded details suggestive of diagnostic confusion between severe and disabling muscle symptoms affecting the lower limbs attributable to an HMG CoA reductase inhibitor with and without ezetimbe and symptoms of neurogenic claudication due to spinal stenosis. The statins were not discontinued promptly leading to prolonged morbidity. Serum creatine kinase levels (CK) were normal in two patients and not recorded for the third. Conclusion: The reports include two safety issues, firstly the need to consider HMG CoA reductase inhibitors as a cause of severe lower limb muscle symptoms even in the presence of spinal stenosis and normal CK levels and the second, the need to measure serum creatine kinase when these symptoms occur to detect progression of myopathy and potentially serious outcomes.
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| 7. |
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| 8. |
- Berg, P. R., et al.
(författare)
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Adaptation to Low Salinity Promotes Genomic Divergence in Atlantic Cod (Gadus morhua L.)
- 2015
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Ingår i: Genome Biology and Evolution. - : Oxford University Press (OUP). - 1759-6653. ; 7:6, s. 1644-1663
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Tidskriftsartikel (refereegranskat)abstract
- How genomic selection enables species to adapt to divergent environments is a fundamental question in ecology and evolution. We investigated the genomic signatures of local adaptation in Atlantic cod (Gadus morhua L.) along a natural salinity gradient, ranging from 35% in the North Sea to 7% within the Baltic Sea. By utilizing a 12K SNPchip, we simultaneously assessed neutral and adaptive genetic divergence across the Atlantic cod genome. Combining outlier analyses with a landscape genomic approach, we identified a set of directionally selected loci that are strongly correlated with habitat differences in salinity, oxygen, and temperature. Our results show that discrete regions within the Atlantic cod genome are subject to directional selection and associated with adaptation to the local environmental conditions in the Baltic-and the North Sea, indicating divergence hitchhiking and the presence of genomic islands of divergence. We report a suite of outlier single nucleotide polymorphisms within or closely located to genes associated with osmoregulation, as well as genes known to play important roles in the hydration and development of oocytes. These genes are likely to have key functions within a general osmoregulatory framework and are important for the survival of eggs and larvae, contributing to the buildup of reproductive isolation between the low-salinity adapted Baltic cod and the adjacent cod populations. Hence, our data suggest that adaptive responses to the environmental conditions in the Baltic Sea may contribute to a strong and effective reproductive barrier, and that Baltic cod can be viewed as an example of ongoing speciation.
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| 9. |
- Bhattacharya, K., et al.
(författare)
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Lactoperoxidase-mediated degradation of single-walled carbon nanotubes in the presence of pulmonary surfactant
- 2015
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Ingår i: Carbon. - : Elsevier BV. - 0008-6223 .- 1873-3891. ; 91, s. 506-517
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Tidskriftsartikel (refereegranskat)abstract
- Carbon nanotubes (CNTs) may elicit inflammatory responses following pulmonary exposure. Conversely, enzymatic biodegradation of CNTs by inflammatory cells has also been reported. The aim of this study was to study the degradation of oxidized single-walled CNTs (ox-SWCNTs) by lactoperoxidase (LPO), a secreted peroxidase present in the airways, and whether pulmonary surfactant affects this biodegradation. To this end, ox-SWCNTs were incubated in vitro with recombinant bovine LPO + H2O2 + NaSCN in the presence and absence of porcine lung surfactant (Curosurf®) and biodegradation was monitored using UV-Vis-NIR spectroscopy, Raman spectroscopy, and scanning electron microscopy. The interaction of recombinant LPO with bundles of ox-SWCNTs was confirmed by atomic force microscopy. Cell-free biodegradation of ox-SWCNTs was also observed ex vivo in murine bronchoalveolar lavage fluid in the presence of H2O2 + NaSCN. Our study provides evidence for biodegradation of ox-SWCNTs with a lung surfactant 'bio-corona' and expands the repertoire of mammalian peroxidases capable of biodegradation of ox-SWCNTs. These findings are relevant to inhalation exposure to these materials, as LPO serves as an important component of the airway defense system.
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