| 1. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 2. |
- Komatsu, Kimberly J., et al.
(författare)
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Global change effects on plant communities are magnified by time and the number of global change factors imposed
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:36, s. 17867-17873
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Tidskriftsartikel (refereegranskat)abstract
- Accurate prediction of community responses to global change drivers (GCDs) is critical given the effects of biodiversity on ecosystem services. There is consensus that human activities are driving species extinctions at the global scale, but debate remains over whether GCDs are systematically altering local communities worldwide. Across 105 experiments that included over 400 experimental manipulations, we found evidence for a lagged response of herbaceous plant communities to GCDs caused by shifts in the identities and relative abundances of species, often without a corresponding difference in species richness. These results provide evidence that community responses are pervasive across a wide variety of GCDs on long-term temporal scales and that these responses increase in strength when multiple GCDs are simultaneously imposed.Global change drivers (GCDs) are expected to alter community structure and consequently, the services that ecosystems provide. Yet, few experimental investigations have examined effects of GCDs on plant community structure across multiple ecosystem types, and those that do exist present conflicting patterns. In an unprecedented global synthesis of over 100 experiments that manipulated factors linked to GCDs, we show that herbaceous plant community responses depend on experimental manipulation length and number of factors manipulated. We found that plant communities are fairly resistant to experimentally manipulated GCDs in the short term (<10 y). In contrast, long-term (≥10 y) experiments show increasing community divergence of treatments from control conditions. Surprisingly, these community responses occurred with similar frequency across the GCD types manipulated in our database. However, community responses were more common when 3 or more GCDs were simultaneously manipulated, suggesting the emergence of additive or synergistic effects of multiple drivers, particularly over long time periods. In half of the cases, GCD manipulations caused a difference in community composition without a corresponding species richness difference, indicating that species reordering or replacement is an important mechanism of community responses to GCDs and should be given greater consideration when examining consequences of GCDs for the biodiversity–ecosystem function relationship. Human activities are currently driving unparalleled global changes worldwide. Our analyses provide the most comprehensive evidence to date that these human activities may have widespread impacts on plant community composition globally, which will increase in frequency over time and be greater in areas where communities face multiple GCDs simultaneously.
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| 3. |
- Lindblad-Toh, Kerstin, et al.
(författare)
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Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
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Tidskriftsartikel (refereegranskat)abstract
- Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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| 4. |
- Afshin, Ashkan, et al.
(författare)
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Health effects of dietary risks in 195 countries, 1990-2017 : a systematic analysis for the Global Burden of Disease Study 2017
- 2019
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 393:10184, s. 1958-1972
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Tidskriftsartikel (refereegranskat)abstract
- Background: Suboptimal diet is an important preventable risk factor for non-communicable diseases (NCDs); however, its impact on the burden of NCDs has not been systematically evaluated. This study aimed to evaluate the consumption of major foods and nutrients across 195 countries and to quantify the impact of their suboptimal intake on NCD mortality and morbidity.Methods: By use of a comparative risk assessment approach, we estimated the proportion of disease-specific burden attributable to each dietary risk factor (also referred to as population attributable fraction) among adults aged 25 years or older. The main inputs to this analysis included the intake of each dietary factor, the effect size of the dietary factor on disease endpoint, and the level of intake associated with the lowest risk of mortality. Then, by use of diseasespecific population attributable fractions, mortality, and disability-adjusted life-years (DALYs), we calculated the number of deaths and DALYs attributable to diet for each disease outcome.Findings: In 2017, 11 million (95% uncertainty interval [UI] 10-12) deaths and 255 million (234-274) DALYs were attributable to dietary risk factors. High intake of sodium (3 million [1-5] deaths and 70 million [34-118] DALYs), low intake of whole grains (3 million [2-4] deaths and 82 million [59-109] DALYs), and low intake of fruits (2 million [1-4] deaths and 65 million [41-92] DALYs) were the leading dietary risk factors for deaths and DALYs globally and in many countries. Dietary data were from mixed sources and were not available for all countries, increasing the statistical uncertainty of our estimates.Interpretation: This study provides a comprehensive picture of the potential impact of suboptimal diet on NCD mortality and morbidity, highlighting the need for improving diet across nations. Our findings will inform implementation of evidence-based dietary interventions and provide a platform for evaluation of their impact on human health annually.
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| 5. |
- Brooke, Darby G., et al.
(författare)
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Antifouling activity of portimine, select semisynthetic analogues, and other microalga-derived spirocyclic imines
- 2018
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Ingår i: Biofouling. - : Informa UK Limited. - 0892-7014 .- 1029-2454. ; 34:8, s. 950-961
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Tidskriftsartikel (refereegranskat)abstract
- © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group. A range of natural products from marine invertebrates, bacteria and fungi have been assessed as leads for nature-inspired antifouling (AF) biocides, but little attention has been paid to microalgal-derived compounds. This study assessed the AF activity of the spirocyclic imine portimine (1), which is produced by the benthic mat-forming dinoflagellate Vulcanodinium rugosum. Portimine displayed potent AF activity in a panel of four macrofouling bioassays (EC 50 0.06–62.5 ng ml −1 ), and this activity was distinct from that of the related compounds gymnodimine-A (2), 13-desmethyl spirolide C (3), and pinnatoxin-F (4). The proposed mechanism of action for portimine is induction of apoptosis, based on the observation that portimine inhibited macrofouling organisms at developmental stages known to involve apoptotic processes. Semisynthetic modification of select portions of the portimine molecule was subsequently undertaken. Observed changes in bioactivity of the resulting semisynthetic analogues of portimine were consistent with portimine’s unprecedented 5-membered imine ring structure playing a central role in its AF activity.
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| 6. |
- Cahill, Patrick, et al.
(författare)
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Nature-Inspired Peptide Antifouling Biocide : Coating Compatibility, Field Validation, and Environmental Stability
- 2023
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Ingår i: ACS Applied Bio Materials. - : American Chemical Society. - 2576-6422. ; 6:6, s. 2415-2425
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Tidskriftsartikel (refereegranskat)abstract
- This study reports the development of a class of eco-friendly antifouling biocides based on a cyclic dipeptide scaffold, 2,5-diketopiperazine (2,5-DKP). The lead compound cyclo(N-Bip-l-Arg-N-Bip-l-Arg) (1) was synthesized in gram amounts and used to assess the compatibility with an ablation/hydration coating, efficacy against biofouling, and biodegradation. Leaching of 1 from the coating into seawater was assessed via a rotating drum method, revealing relatively stable and predictable leaching rates under dynamic shear stress conditions (36.1 ± 19.7 to 25.2 ± 9.1 ng-1 cm-2 day-1) but low or no leaching under static conditions. The coatings were further analyzed using time-of-flight secondary ion mass spectrometry (ToF-SIMS), with 1 seen to localize at the surface of the coating in a surfactant-like fashion. When coatings were deployed in the ocean, detectable reductions in biofouling development were measured for up to 11 weeks. After this time, biofouling overwhelmed the performance of the coating, consistent with leaching kinetics. Biodegradation of 1 in seawater was assessed using theoretical oxygen demand and analytical quantification. Masking effects were observed at higher concentrations of 1 due to antimicrobial properties, but half-lives were calculated ranging from 13.4 to 16.2 days. The results can rationally inform future development toward commercial antifouling products.
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| 7. |
- Cuddihy, Laury, et al.
(författare)
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Vertebral Body Stapling versus Bracing for Patients with High-Risk Moderate Idiopathic Scoliosis.
- 2015
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Ingår i: BioMed research international. - : Hindawi Limited. - 2314-6141 .- 2314-6133. ; 2015
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Tidskriftsartikel (refereegranskat)abstract
- We report a comparison study of vertebral body stapling (VBS) versus a matched bracing cohort for immature patients with moderate (25 to 44°) idiopathic scoliosis (IS).42 of 49 consecutive patients (86%) with IS were treated with VBS and followed for a minimum of 2 years. They were compared to 121 braced patients meeting identical inclusion criteria. 52 patients (66 curves) were matched according to age at start of treatment (10.6 years versus 11.1 years, resp. [P = 0.07]) and gender.For thoracic curves 25-34°, VBS had a success rate (defined as curve progression <10°) of 81% versus 61% for bracing (P = 0.16). In thoracic curves 35-44°, VBS and bracing both had a poor success rate. For lumbar curves, success rates were similar in both groups for curves measuring 25-34°.In this comparison of two cohorts of patients with high-risk (Risser 0-1) moderate IS (25-44°), in smaller thoracic curves (25-34°) VBS provided better results as a clinical trend as compared to bracing. VBS was found not to be effective for thoracic curves ≥35°. For lumbar curves measuring 25-34°, results appear to be similar for both VBS and bracing, at 80% success.
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| 8. |
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| 9. |
- Kappos, Ludwig, et al.
(författare)
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Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study
- 2018
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 391, s. 1263-1273
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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.
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| 10. |
- Moodie, Lindon W. K., et al.
(författare)
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Probing the Structure-Activity Relationship of the Natural Antifouling Agent Polygodial against both Micro- and Macrofoulers by Semisynthetic Modification
- 2017
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Ingår i: Journal of natural products (Print). - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 80:2, s. 515-525
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Tidskriftsartikel (refereegranskat)abstract
- The current study represents the first comprehensive investigation into the general antifouling activities of the natural drimane sesquiterpene polygodial. Previous studies have highlighted a high antifouling effect toward macrofoulers, such as ascidians, tubeworms, and mussels, but no reports about the general antifouling effect of polygodial have been communicated before. To probe the structural and chemical basis for antifouling activity, a library of 11 polygodial analogues was prepared by semisynthesis. The library was designed to yield derivatives with ranging polarities and the ability to engage in both covalent and noncovalent interactions, while still remaining within the drimane sesquiterpene scaffold. The prepared compounds were screened against 14 relevant marine micro- and macrofouling species. Several of the polygodial analogues displayed inhibitory activities at sub-microgram/mL concentrations. These antifouling effects were most pronounced against the macrofouling ascidian Ciona savignyi and the barnacle Balanus improvisus, with inhibitory activities observed for selected compounds comparable or superior to several commercial antifouling products. The inhibitory activity against the microfouling bacteria and microalgae was reversible and significantly less pronounced than for the macrofoulers. This study illustrates that the macro- and microfoulers are targeted by the compounds via different mechanisms.
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