| 1. |
- Fages, A., et al.
(author)
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Tracking Five Millennia of Horse Management with Extensive Ancient Genome Time Series
- 2019
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In: Cell. - : Elsevier BV. - 0092-8674. ; 177:6
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Journal article (peer-reviewed)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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| 2. |
- Andõn, F. T., et al.
(author)
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Biodegradation of Single-Walled Carbon Nanotubes by Eosinophil Peroxidase
- 2013
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In: Small. - : Wiley-VCH Verlagsgesellschaft. - 1613-6810 .- 1613-6829. ; 9:16, s. 2721-2729
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Journal article (peer-reviewed)abstract
- Eosinophil peroxidase (EPO) is one of the major oxidant-producing enzymes during inflammatory states in the human lung. The degradation of single-walled carbon nanotubes (SWCNTs) upon incubation with human EPO and H2O 2 is reported. Biodegradation of SWCNTs is higher in the presence of NaBr, but neither EPO alone nor H2O2 alone caused the degradation of nanotubes. Molecular modeling reveals two binding sites for SWCNTs on EPO, one located at the proximal side (same side as the catalytic site) and the other on the distal side of EPO. The oxidized groups on SWCNTs in both cases are stabilized by electrostatic interactions with positively charged residues. Biodegradation of SWCNTs can also be executed in an ex vivo culture system using primary murine eosinophils stimulated to undergo degranulation. Biodegradation is proven by a range of methods including transmission electron microscopy, UV-visible-NIR spectroscopy, Raman spectroscopy, and confocal Raman imaging. Thus, human EPO (in vitro) and ex vivo activated eosinophils mediate biodegradation of SWCNTs: an observation that is relevant to pulmonary responses to these materials. Human eosinophil peroxidase (EPO) is able to degrade SWCNTs in vitro in the presence of H2O2. EPO is one of the major oxidant-generating enzymes present in human lungs during inflammatory states. The biodegradation of SWCNTs is evidenced also in an ex vivo culture system using primary murine eosinophils stimulated to undergo degranulation. These results are relevant to potential respiratory exposure to carbon nanotubes.
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| 3. |
- Hetland, M. L., et al.
(author)
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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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In: Bmj-British Medical Journal. - : BMJ. - 1756-1833. ; 371
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Journal article (peer-reviewed)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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| 4. |
- Bhattacharya, K., et al.
(author)
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Lactoperoxidase-mediated degradation of single-walled carbon nanotubes in the presence of pulmonary surfactant
- 2015
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In: Carbon. - : Elsevier BV. - 0008-6223 .- 1873-3891. ; 91, s. 506-517
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Journal article (peer-reviewed)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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| 5. |
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| 6. |
- Ungvari, Zoltan, et al.
(author)
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Resistance to Genotoxic Stresses in Arctica islandica, the Longest Living Noncolonial Animal : Is Extreme Longevity Associated With a Multistress Resistance Phenotype?
- 2013
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In: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press. - 1079-5006 .- 1758-535X. ; 68:5, s. 521-529
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Journal article (peer-reviewed)abstract
- Bivalve molluscs are newly discovered models of successful aging. Here, we test the hypothesis that extremely long-lived bivalves are not uniquely resistant to oxidative stressors (eg, tert-butyl hydroperoxide, as demonstrated in previous studies) but exhibit a multistress resistance phenotype. We contrasted resistance (in terms of organismal mortality) to genotoxic stresses (including topoisomerase inhibitors, agents that cross-link DNA or impair genomic integrity through DNA alkylation or methylation) and to mitochondrial oxidative stressors in three bivalve mollusc species with dramatically differing life spans: Arctica islandica (ocean quahog), Mercenaria mercenaria (northern quahog), and the Atlantic bay scallop, Argopecten irradians irradians (maximum species life spans: >500, >100, and ~2 years, respectively). With all stressors, the short-lived A i irradians were significantly less resistant than the two longer lived species. Arctica islandica were consistently more resistant than M mercenaria to mortality induced by oxidative stressors as well as DNA methylating agent nitrogen mustard and the DNA alkylating agent methyl methanesulfonate. The same trend was not observed for genotoxic agents that act through cross-linking DNA. In contrast, M mercenaria tended to be more resistant to epirubicin and genotoxic stressors, which cause DNA damage by inhibiting topoisomerases. To our knowledge, this is the first study comparing resistance to genotoxic stressors in bivalve mollusc species with disparate longevities. In line with previous studies of comparative stress resistance and longevity, our data extends, at least in part, the evidence for the hypothesis that an association exists between longevity and a general resistance to multiplex stressors, not solely oxidative stress. This work also provides justification for further investigation into the interspecies differences in stress response signatures induced by a diverse array of stressors in short-lived and long-lived bivalves, including pharmacological agents that elicit endoplasmic reticulum stress and cellular stress caused by activation of innate immunity.
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| 9. |
- Atmore, L. M., et al.
(author)
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Population dynamics of Baltic herring since the Viking Age revealed by ancient DNA and genomics
- 2022
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In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - : Proceedings of the National Academy of Sciences. ; 119:45
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Journal article (peer-reviewed)abstract
- The world's oceans are currently facing major stressors in the form of overexploitation and anthropogenic climate change. The Baltic Sea was home to the first "industrial" fishery ∼800 y ago targeting the Baltic herring, a species that is still economically and culturally important today. Yet, the early origins of marine industries and the long-term ecological consequences of historical and contemporary fisheries remain debated. Here, we study long-term population dynamics of Baltic herring to evaluate the past impacts of humans on the marine environment. We combine modern whole-genome data with ancient DNA (aDNA) to identify the earliest-known long-distance herring trade in the region, illustrating that extensive fish trade began during the Viking Age. We further resolve population structure within the Baltic and observe demographic independence for four local herring stocks over at least 200 generations. It has been suggested that overfishing at Øresund in the 16th century resulted in a demographic shift from autumn-spawning to spring-spawning herring dominance in the Baltic. We show that while the Øresund fishery had a negative impact on the western Baltic herring stock, the demographic shift to spring-spawning dominance did not occur until the 20th century. Instead, demographic reconstructions reveal population trajectories consistent with expected impacts of environmental change and historical reports on shifting fishing targets over time. This study illustrates the joint impact of climate change and human exploitation on marine species as well as the role historical ecology can play in conservation and management policies.
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| 10. |
- Berg, P. R., et al.
(author)
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Adaptation to Low Salinity Promotes Genomic Divergence in Atlantic Cod (Gadus morhua L.)
- 2015
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In: Genome Biology and Evolution. - : Oxford University Press (OUP). - 1759-6653. ; 7:6, s. 1644-1663
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Journal article (peer-reviewed)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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| 11. |
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| 12. |
- Bhattacharya, Kunal, et al.
(author)
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Enzymatic 'stripping' and degradation of PEGylated carbon nanotubes
- 2014
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In: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 6:24, s. 14686-14690
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Journal article (peer-reviewed)abstract
- Single-walled carbon nanotubes (SWCNTs) coated or functionalized with PEG chains of different molecular weight were assessed for their propensity to undergo biodegradation under in vitro conditions using recombinant myeloperoxidase (MPO) or ex vivo using freshly isolated primary human neutrophils. Our findings suggest that under natural conditions, a combined process of 'stripping' (i.e., defunctionalization) and biodegradation of PEG-SWCNTs might occur and that PEG-SWCNTs are a promising-and degradable-nanomedicine vector.
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| 20. |
- Star, B., et al.
(author)
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Ancient DNA reveals the Arctic origin of Viking Age cod from Haithabu, Germany
- 2017
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 114:34, s. 9152-9157
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Journal article (peer-reviewed)abstract
- Knowledge of the range and chronology of historic trade and long-distance transport of natural resources is essential for determining the impacts of past human activities on marine environments. However, the specific biological sources of imported fauna are often difficult to identify, in particular if species have a wide spatial distribution and lack clear osteological or isotopic differentiation between populations. Here, we report that ancient fish-bone remains, despite being porous, brittle, and light, provide an excellent source of endogenous DNA (15-46%) of sufficient quality for whole-genome reconstruction. By comparing ancient sequence data to that of modern specimens, we determine the biological origin of 15 Viking Age (800-1066 CE) and subsequent medieval (1066-1280 CE) Atlantic cod (Gadus morhua) specimens from excavation sites in Germany, Norway, and the United Kingdom. Archaeological context indicates that one of these sites was a fishing settlement for the procurement of local catches, whereas the other localities were centers of trade. Fish from the trade sites show a mixed ancestry and are statistically differentiated from local fish populations. Moreover, Viking Age samples from Haithabu, Germany, are traced back to the North East Arctic Atlantic cod population that has supported the Lofoten fisheries of Norway for centuries. Our results resolve a long-standing controversial hypothesis and indicate that the marine resources of the North Atlantic Ocean were used to sustain an international demand for protein as far back as the Viking Age.
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| 21. |
- Star, Kristina, et al.
(author)
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Pneumonia following antipsychotic prescriptions in electronic health records : a patient safety concern?
- 2010
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In: British Journal of General Practice. - 0960-1643 .- 1478-5242. ; 60:579, s. 749-755
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Journal article (peer-reviewed)abstract
- Background In screening the Intercontinental Medical Statistics (IMS) Health Disease Analyzer database of GP records from the UK, an increased registration of pneumonia subsequent to the prescription of some antipsychotic medicines was identified. Aim To investigate the temporal pattern between antipsychotic prescriptions and pneumonia with respect to age, type of pneumonia and other chest infections, and antipsychotic class. Design of study Self-controlled cohort analysis. Setting Electronic health records from the UK IMS Health Disease Analyzer database. Method Three groups of pneumonia-related International Classification of Diseases (ICD)-10 terms and prescriptions of atypical and conventional antipsychotic medicines were studied. Separate analyses were carried out for patients aged >= 65 years. The observed rate of pneumonia terms registered in different time periods in connection to antipsychotic prescriptions was contrasted to the overall rate of pneumonia terms relative to prescriptions of other drugs in the same dataset. Results In patients aged >= 65 years, an increased registration of a group of terms defined as 'acute chest infections', after atypical antipsychotic prescriptions, was identified. The corresponding increase after conventional antipsychotic prescriptions was much smaller. Bronchopneumonia had a striking increase after both atypical and conventional antipsychotic prescriptions, and was commonly recorded with fatal outcome. Few registrations of hypostatic. pneumonia were noted. Patients aged <65 years did not have a higher rate of acute chest infections after receiving antipsychotic prescriptions. Conclusion The consistent pattern of an increased rate of chest infections after atypical antipsychotic prescriptions in older people seen in this outpatient study, together with the higher risk shown in a previous study on hospitalised patients, suggests a causal relationship. This is of importance since bronchopneumonia seems highly linked to fatal outcome. In the absence of a mechanism, further investigation of the role of antipsychotics in older people is needed.
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| 22. |
- Star, Kristina, et al.
(author)
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Rhabdomyolysis Reported for Children and Adolescents Treated with Antipsychotic Medicines : A Case Series Analysis
- 2012
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In: Journal of child and adolescent psychopharmacology. - : Mary Ann Liebert Inc. - 1044-5463 .- 1557-8992. ; 22:6, s. 440-451
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Journal article (peer-reviewed)abstract
- Objective: Rhabdomyolysis is a rare and potentially serious adverse drug reaction (ADR) to antipsychotic medicines. The aim of this study was to investigate the clinical circumstances surrounding the diagnosis of rhabdomyolysis in children and adolescents treated with antipsychotic medicines. We also critically reviewed individual case safety reports (ICSRs) of suspected ADRs to evaluate how clinically useful they can be in a case series analysis. Methods: This was a descriptive and an exploratory study. Published case reports and ICSRs from the World Health Organization (WHO) Global ICSR database, VigiBase, reported with rhabdomyolysis and antipsychotic medicines for patients <= 17 years years of age were described. Reporting patterns of ICSRs with rhabdomyolysis and antipsychotic medicines were explored in VigiBase for children and adolescents and for adults. The VigiBase ICSRs were also systematically evaluated regarding the report content. Results: Of the 26 evaluated reports, 6 co-reported neuroleptic malignant syndrome (NMS) and 20 reports concerned rhabdomyolysis in the absence of NMS. The reported suspected antipsychotic medicines for these 20 reports were olanzapine, risperidone, haloperidol, paliperidone, quetiapine, clozapine, cyamemazine, and aripiprazole. In VigiBase, rhabdomyolysis (in the absence of NMS) was reported more frequently with olanzapine relative to all reports for children and adolescents with antipsychotic medicines. In the range of events that preceded rhabdomyolysis, muscle pains and abdominal pain were commonly recorded to have started during the week prior to the diagnosis. Other preceding symptoms were general weakness and dark urine. Onset of rhabdomyolysis for most patients occurred at any time within 2 months of starting antipsychotic treatment, in several cases triggered by changes to the patient's drug therapy or known risk factors of rhabdomyolysis. It was found that ICSRs can contribute with additional information, but that access to free text and narratives were crucial in order to capture clinically useful features of rhabdomyolysis. Conclusion: Monitoring of children and adolescents needs to be intensified during dose increases, or when a new, added, or switched antipsychotic medicine is introduced to their drug regimen, and during exposure to known risk factors for rhabdomyolysis. The development of seemingly nonserious events, such as abdominal pain, muscle pain, weakness, and dark urine, should be followed up during antipsychotic use, as they might be precursory events to rhabdomyolysis that eventually could develop into acute renal failure.
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