| 1. |
- Fenstermacher, M.E., et al.
(författare)
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DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
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Tidskriftsartikel (refereegranskat)abstract
- DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
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| 2. |
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| 3. |
- Griffin, M. J., et al.
(författare)
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The Herschel-SPIRE instrument and its in-flight performance
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L3-
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Tidskriftsartikel (refereegranskat)abstract
- The Spectral and Photometric Imaging REceiver (SPIRE), is the Herschel Space Observatory`s submillimetre camera and spectrometer. It contains a three-band imaging photometer operating at 250, 350 and 500 mu m, and an imaging Fourier-transform spectrometer (FTS) which covers simultaneously its whole operating range of 194-671 mu m (447-1550 GHz). The SPIRE detectors are arrays of feedhorn-coupled bolometers cooled to 0.3 K. The photometer has a field of view of 4' x 8', observed simultaneously in the three spectral bands. Its main operating mode is scan-mapping, whereby the field of view is scanned across the sky to achieve full spatial sampling and to cover large areas if desired. The spectrometer has an approximately circular field of view with a diameter of 2.6'. The spectral resolution can be adjusted between 1.2 and 25 GHz by changing the stroke length of the FTS scan mirror. Its main operating mode involves a fixed telescope pointing with multiple scans of the FTS mirror to acquire spectral data. For extended source measurements, multiple position offsets are implemented by means of an internal beam steering mirror to achieve the desired spatial sampling and by rastering of the telescope pointing to map areas larger than the field of view. The SPIRE instrument consists of a cold focal plane unit located inside the Herschel cryostat and warm electronics units, located on the spacecraft Service Module, for instrument control and data handling. Science data are transmitted to Earth with no on-board data compression, and processed by automatic pipelines to produce calibrated science products. The in-flight performance of the instrument matches or exceeds predictions based on pre-launch testing and modelling: the photometer sensitivity is comparable to or slightly better than estimated pre-launch, and the spectrometer sensitivity is also better by a factor of 1.5-2.
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| 4. |
- De Leoz, M. L. A., et al.
(författare)
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NIST Interlaboratory Study on Glycosylation Analysis of Monoclonal Antibodies: Comparison of Results from Diverse Analytical Methods
- 2020
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476. ; 19:1, s. 11-30
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Tidskriftsartikel (refereegranskat)abstract
- A broad-based interlaboratory study of glycosylation profiles of a reference and modified IgG antibody involving 103 reports from 76 laboratories. Glycosylation is a topic of intense current interest in the development of biopharmaceuticals because it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy-six laboratories from industry, university, research, government, and hospital sectors in Europe, North America, Asia, and Australia submitted a total of 103 reports on glycan distributions. The principal objective of this study was to report and compare results for the full range of analytical methods presently used in the glycosylation analysis of mAbs. Therefore, participation was unrestricted, with laboratories choosing their own measurement techniques. Protein glycosylation was determined in various ways, including at the level of intact mAb, protein fragments, glycopeptides, or released glycans, using a wide variety of methods for derivatization, separation, identification, and quantification. Consequently, the diversity of results was enormous, with the number of glycan compositions identified by each laboratory ranging from 4 to 48. In total, one hundred sixteen glycan compositions were reported, of which 57 compositions could be assigned consensus abundance values. These consensus medians provide community-derived values for NISTmAb PS. Agreement with the consensus medians did not depend on the specific method or laboratory type. The study provides a view of the current state-of-the-art for biologic glycosylation measurement and suggests a clear need for harmonization of glycosylation analysis methods.
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| 5. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 6. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 7. |
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| 8. |
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| 9. |
- Stoffel, M. A., et al.
(författare)
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Demographic histories and genetic diversity across pinnipeds are shaped by human exploitation, ecology and life-history
- 2018
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- A central paradigm in conservation biology is that population bottlenecks reduce genetic diversity and population viability. In an era of biodiversity loss and climate change, understanding the determinants and consequences of bottlenecks is therefore an important challenge. However, as most studies focus on single species, the multitude of potential drivers and the consequences of bottlenecks remain elusive. Here, we combined genetic data from over 11,000 individuals of 30 pinniped species with demographic, ecological and life history data to evaluate the consequences of commercial exploitation by 18th and 19th century sealers. We show that around one third of these species exhibit strong signatures of recent population declines. Bottleneck strength is associated with breeding habitat and mating system variation, and together with global abundance explains much of the variation in genetic diversity across species. Overall, bottleneck intensity is unrelated to IUCN status, although the three most heavily bottlenecked species are endangered. Our study reveals an unforeseen interplay between human exploitation, animal biology, demographic declines and genetic diversity.
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| 10. |
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| 11. |
- Martin, DP, et al.
(författare)
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Selection analysis identifies unusual clustered mutational changes in Omicron lineage BA.1 that likely impact Spike function
- 2022
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Ingår i: bioRxiv : the preprint server for biology. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Among the 30 non-synonymous nucleotide substitutions in the Omicron S-gene are 13 that have only rarely been seen in other SARS-CoV-2 sequences. These mutations cluster within three functionally important regions of the S-gene at sites that will likely impact (i) interactions between subunits of the Spike trimer and the predisposition of subunits to shift from down to up configurations, (ii) interactions of Spike with ACE2 receptors, and (iii) the priming of Spike for membrane fusion. We show here that, based on both the rarity of these 13 mutations in intrapatient sequencing reads and patterns of selection at the codon sites where the mutations occur in SARS-CoV-2 and related sarbecoviruses, prior to the emergence of Omicron the mutations would have been predicted to decrease the fitness of any genomes within which they occurred. We further propose that the mutations in each of the three clusters therefore cooperatively interact to both mitigate their individual fitness costs, and adaptively alter the function of Spike. Given the evident epidemic growth advantages of Omicron over all previously known SARS-CoV-2 lineages, it is crucial to determine both how such complex and highly adaptive mutation constellations were assembled within the Omicron S-gene, and why, despite unprecedented global genomic surveillance efforts, the early stages of this assembly process went completely undetected.
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| 12. |
- Shafer, Aaron B. A., et al.
(författare)
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Genomics and the challenging translation into conservation practice
- 2015
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Ingår i: Trends in Ecology & Evolution. - : Elsevier. - 0169-5347 .- 1872-8383. ; 30:2, s. 78-87
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Tidskriftsartikel (refereegranskat)abstract
- The global loss of biodiversity continues at an alarming rate. Genomic approaches have been suggested as a promising tool for conservation practice as scaling up to genome-wide data can improve traditional conservation genetic inferences and provide qualitatively novel insights. However, the generation of genomic data and subsequent analyses and interpretations remain challenging and largely confined to academic research in ecology and evolution. This generates a gap between basic research and applicable solutions for conservation managers faced with multifaceted problems. Before the real-world conservation potential of genomic research can be realized, we suggest that current infrastructures need to be modified, methods must mature, analytical pipelines need to be developed, and successful case studies must be disseminated to practitioners.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- Shafer, Aaron B A, et al.
(författare)
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Reply to Garner et al
- 2016
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Ingår i: Trends in Ecology & Evolution. - : Elsevier BV. - 0169-5347 .- 1872-8383. ; 31:2, s. 83-84
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Tidskriftsartikel (refereegranskat)
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| 17. |
- Walker, Anthony P., et al.
(författare)
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Integrating the evidence for a terrestrial carbon sink caused by increasing atmospheric CO2
- 2021
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Ingår i: New Phytologist. - : John Wiley & Sons. - 0028-646X .- 1469-8137. ; 229:5, s. 2413-2445
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Tidskriftsartikel (refereegranskat)abstract
- Atmospheric carbon dioxide concentration ([CO2]) is increasing, which increases leaf‐scale photosynthesis and intrinsic water‐use efficiency. These direct responses have the potential to increase plant growth, vegetation biomass, and soil organic matter; transferring carbon from the atmosphere into terrestrial ecosystems (a carbon sink). A substantial global terrestrial carbon sink would slow the rate of [CO2] increase and thus climate change. However, ecosystem CO2 responses are complex or confounded by concurrent changes in multiple agents of global change and evidence for a [CO2]‐driven terrestrial carbon sink can appear contradictory. Here we synthesize theory and broad, multidisciplinary evidence for the effects of increasing [CO2] (iCO2) on the global terrestrial carbon sink. Evidence suggests a substantial increase in global photosynthesis since pre‐industrial times. Established theory, supported by experiments, indicates that iCO2 is likely responsible for about half of the increase. Global carbon budgeting, atmospheric data, and forest inventories indicate a historical carbon sink, and these apparent iCO2 responses are high in comparison to experiments and predictions from theory. Plant mortality and soil carbon iCO2 responses are highly uncertain. In conclusion, a range of evidence supports a positive terrestrial carbon sink in response to iCO2, albeit with uncertain magnitude and strong suggestion of a role for additional agents of global change.
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| 18. |
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Currier, Russell W, et al.
(författare)
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The evolution of infectious agents in relation to sex in animals and humans: brief discussions of some individual organisms.
- 2011
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 1749-6632 .- 0077-8923. ; 1230, s. 74-107, s. 74-107
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Forskningsöversikt (refereegranskat)abstract
- The following series of concise summaries addresses the evolution of infectious agents in relation to sex in animals and humans from the perspective of three specific questions: (1) what have we learned about the likely origin and phylogeny, up to the establishment of the infectious agent in the genital econiche, including the relative frequency of its sexual transmission; (2) what further research is needed to provide additional knowledge on some of these evolutionary aspects; and (3) what evolutionary considerations might aid in providing novel approaches to the more practical clinical and public health issues facing us currently and in the future?
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Hoots, W. K., et al.
(författare)
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Secondary prophylaxis with recombinant activated factor VII improves health-related quality of life of haemophilia patients with inhibitors
- 2008
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 14:3, s. 466-466
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Tidskriftsartikel (refereegranskat)abstract
- Haemophilia patients with inhibitors characteristically have impaired joint function and reduced health-related quality of life (HRQoL). This analysis examined whether secondary prophylaxis with recombinant activated factor VII (rFVIIa) improves HRQoL vs. conventional on-demand therapy in patients with haemophilia with inhibitors and frequent bleeds. After a 3-month preprophylaxis period, 22 patients received daily rFVIIa prophylaxis (90 or 270 mu g kg(-1)) for 3 months, followed by 3 months' postprophylaxis. Days of hospitalization, absence from school/work and mobility aids requirements were recorded. HRQoL was assessed by EuroQoL (EQ-5D) questionnaire, visual analogue scale (VAS), derived Time to Trade-Off (TTO) scores and Quality Adjusted Life Years (QALYs). rFVIIa prophylaxis significantly (P < 0.0001) reduced bleeding frequency vs. prior on-demand therapy. Hospitalization (5.9% vs. 13.5%; P = 0.0026) and absenteeism from school/work (16.7% vs. 38.7%; P = 0.0127) decreased during prophylaxis; these effects tended to be maintained during postprophylaxis. HRQoL (evaluated by EQ-5D) tended to improve during and after rFVIIa prophylaxis. Notably, pain decreased and mobility increased in 40.9% and 27.3% of patients, respectively, at the end of the postprophylaxis period vs. preprophylaxis. Median VAS score increased from 66 to 73 (P = 0.048), and TTO scores suggested better HRQoL (0.62 vs. 0.76; P = 0.054) during postprophylaxis than preprophylaxis. Small to moderate changes in effect sizes were reported for VAS and TTO scores. Median QALYs were 0.68 (VAS) and 0.73 (TTO). Reductions in bleeding frequency with secondary rFVIIa prophylaxis were associated with improved HRQoL vs. on-demand therapy.
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| 27. |
- Klewe, C., et al.
(författare)
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Observation of coherently coupled cation spin dynamics in an insulating ferrimagnetic oxide
- 2023
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Ingår i: Applied Physics Letters. - : American Institute of Physics (AIP). - 0003-6951 .- 1077-3118. ; 122:13
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Tidskriftsartikel (refereegranskat)abstract
- Many technologically useful magnetic oxides are ferrimagnetic insulators, which consist of chemically distinct cations. Here, we examine the spin dynamics of different magnetic cations in ferrimagnetic NiZnAl-ferrite (Ni0.65Zn0.35Al0.8Fe1.2O4) under continuous microwave excitation. Specifically, we employ time-resolved x-ray ferromagnetic resonance to separately probe Fe2+/3+ and Ni2+ cations on different sublattice sites. Our results show that the precessing cation moments retain a rigid, collinear configuration to within ≈2°. Moreover, the effective spin relaxation is identical to within <10% for all magnetic cations in the ferrite. Thus, we validate the oft-assumed “ferromagnetic-like” dynamics in the resonantly driven ferrimagnetic oxide: the magnetic moments from different cations precess as a coherent, collective magnetization, despite the high contents of nonmagnetic Zn2+ and Al3+ diluting the exchange interactions.
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| 28. |
- Manasa, Justen, et al.
(författare)
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Evolution of gag and gp41 in Patients Receiving Ritonavir-Boosted Protease Inhibitors
- 2017
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Ingår i: Scientific Reports. - London : Nature Publishing Group. - 2045-2322. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Several groups have proposed that genotypic determinants in gag and the gp41 cytoplasmic domain (gp41-CD) reduce protease inhibitor (PI) susceptibility without PI-resistance mutations in protease. However, no gag and gp41-CD mutations definitively responsible for reduced PI susceptibility have been identified in individuals with virological failure (VF) while receiving a boosted PI (PI/r)-containing regimen. To identify gag and gp41 mutations under selective PI pressure, we sequenced gag and/or gp41 in 61 individuals with VF on a PI/r (n = 40) or NNRTI (n = 20) containing regimen. We quantified nonsynonymous and synonymous changes in both genes and identified sites exhibiting signal for directional or diversifying selection. We also used published gag and gp41 polymorphism data to highlight mutations displaying a high selection index, defined as changing from a conserved to an uncommon amino acid. Many amino acid mutations developed in gag and in gp41-CD in both the PI- and NNRTI-treated groups. However, in neither gene, were there discernable differences between the two groups in overall numbers of mutations, mutations displaying evidence of diversifying or directional selection, or mutations with a high selection index. If gag and/or gp41 encode PI-resistance mutations, they may not be confined to consistent mutations at a few sites. © 2017 The Author(s).
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| 29. |
- Shafer, Aaron B. A., et al.
(författare)
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Demographic inferences using short-read genomic data in an approximate Bayesian computation framework : in silico evaluation of power, biases and proof of concept in Atlantic walrus
- 2015
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Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 24:2, s. 328-345
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Tidskriftsartikel (refereegranskat)abstract
- Approximate Bayesian computation (ABC) is a powerful tool for model-based inference of demographic histories from large genetic data sets. For most organisms, its implementation has been hampered by the lack of sufficient genetic data. Genotyping-by-sequencing (GBS) provides cheap genome-scale data to fill this gap, but its potential has not fully been exploited. Here, we explored power, precision and biases of a coalescent-based ABC approach where GBS data were modelled with either a population mutation parameter () or a fixed site (FS) approach, allowing single or several segregating sites per locus. With simulated data ranging from 500 to 50000 loci, a variety of demographic models could be reliably inferred across a range of timescales and migration scenarios. Posterior estimates were informative with 1000 loci for migration and split time in simple population divergence models. In more complex models, posterior distributions were wide and almost reverted to the uninformative prior even with 50000 loci. ABC parameter estimates, however, were generally more accurate than an alternative composite-likelihood method. Bottleneck scenarios proved particularly difficult, and only recent bottlenecks without recovery could be reliably detected and dated. Notably, minor-allele-frequency filters - usual practice for GBS data - negatively affected nearly all estimates. With this in mind, we used a combination of FS and approaches on empirical GBS data generated from the Atlantic walrus (Odobenus rosmarus rosmarus), collectively providing support for a population split before the last glacial maximum followed by asymmetrical migration and a high Arctic bottleneck. Overall, this study evaluates the potential and limitations of GBS data in an ABC-coalescence framework and proposes a best-practice approach.
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| 30. |
- von Rönn, Jan A. C., et al.
(författare)
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Disruptive selection without genome-wide evolution across a migratory divide
- 2016
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Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 25:11, s. 2529-2541
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Tidskriftsartikel (refereegranskat)abstract
- Transcontinental migration is a fascinating example of how animals can respond to climatic oscillation. Yet, quantitative data on fitness components are scarce, and the resulting population genetic consequences are poorly understood. Migratory divides, hybrid zones with a transition in migratory behaviour, provide a natural setting to investigate the micro-evolutionary dynamics induced by migration under sympatric conditions. Here, we studied the effects of migratory programme on survival, trait evolution and genome-wide patterns of population differentiation in a migratory divide of European barn swallows. We sampled a total of 824 individuals from both allopatric European populations wintering in central and southern Africa, respectively, along with two mixed populations from within the migratory divide. While most morphological characters varied by latitude consistent with Bergmann's rule, wing length co-varied with distance to wintering grounds. Survival data collected during a 5-year period provided strong evidence that this covariance is repeatedly generated by disruptive selection against intermediate phenotypes. Yet, selection-induced divergence did not translate into genome-wide genetic differentiation as assessed by microsatellites, mtDNA and >20 000 genome-wide SNP markers; nor did we find evidence of local genomic selection between migratory types. Among breeding populations, a single outlier locus mapped to the BUB1 gene with a role in mitotic and meiotic organization. Overall, this study provides evidence for an adaptive response to variation in migration behaviour continuously eroded by gene flow under current conditions of non-assortative mating. It supports the theoretical prediction that population differentiation is difficult to achieve under conditions of gene flow despite measurable disruptive selection.
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| 31. |
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| 32. |
- Cai, Ruibo, et al.
(författare)
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Recombination and selection in the major histocompatibility complex of the endangered forest musk deer (Moschus berezovskii)
- 2015
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- The forest musk deer (Moschus berezovskii) is a high elevation species distributed across western China and northern Vietnam. Once abundant, habitat loss and poaching has led to a dramatic decrease in population numbers prompting the IUCN to list the species as endangered. Here, we characterized the genetic diversity of a Major Histocompatibility Complex (MHC) locus and teased apart driving factors shaping its variation. Seven DRB exon 2 alleles were identified among a group of randomly sampled forest musk deer from a captive population in the Sichuan province of China. Compared to other endangered or captive ungulates, forest musk deer have relatively low levels of MHC genetic diversity. Non-synonymous substitutions primarily occurred in the putative peptide-binding region (PBR), with analyses suggesting that recombination and selection has shaped the genetic diversity across the locus. Specifically, inter-allelic recombination generated novel allelic combinations, with evidence for both positive selection acting on the PBR and negative selection on the non-PBR. An improved understanding of functional genetic variability of the MHC will facilitate better design and management of captive breeding programs for this endangered species.
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| 33. |
- Edwards, Jennifer L., et al.
(författare)
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Potent In Vitro and Ex Vivo Anti-Gonococcal Activity of the RpoB Inhibitor Corallopyronin A
- 2022
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Ingår i: mSphere. - : American Society for Microbiology. - 2379-5042. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- Gonorrhea remains a major global public health problem because of the high incidence of infection (estimated 82 million cases in 2020) and the emergence and spread of Neisseria gonorrhoeae strains resistant to previous and current antibiotics used to treat infections. Given the dearth of new antibiotics that are likely to enter clinical practice in the near future, there is concern that cases of untreatable gonorrhea might emerge. In response to this crisis, the World Health Organization (WHO), in partnership with the Global Antibiotic Research and Development Partnership (GARDP), has made the search for and development of new antibiotics against N. gonorrhoeae a priority. Ideally, these antibiotics should also be active against other sexually transmitted organisms, such as Chlamydia trachomatis and/or Mycoplasma genitalium, which are often found with N. gonorrhoeae as co-infections. Corallopyronin A is a potent antimicrobial that exhibits activity against Chlamydia spp. and inhibits transcription by binding to the RpoB switch region. Accordingly, we tested the effectiveness of corallopyronin A against N. gonorrhoeae. We also examined the mutation frequency and modes of potential resistance against corallopyronin A. We report that corallopyronin A has potent antimicrobial action against antibiotic-susceptible and antibiotic-resistant N. gonorrhoeae strains and could eradicate gonococcal infection of cultured, primary human cervical epithelial cells. Critically, we found that spontaneous corallopyronin A-resistant mutants of N. gonorrhoeae are exceedingly rare (≤10-10) when selected at 4× the MIC. Our results support pre-clinical studies aimed at developing corallopyronin A for gonorrheal treatment regimens.IMPORTANCE The high global incidence of gonorrhea, the lack of a protective vaccine, and the emergence of N. gonorrhoeae strains expressing resistance to currently used antibiotics demand that new treatment options be developed. Accordingly, we investigated whether corallopyronin A, an antibiotic which is effective against other pathogens, including C. trachomatis, which together with gonococci frequently cause co-infections in humans, could exert anti-gonococcal action in vitro and ex vivo, and potential resistance emergence. We propose that corallopyronin A be considered a potential future treatment option for gonorrhea because of its potent activity, low resistance development, and recent advances in scalable production.
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| 34. |
- Higley, Daniel J., et al.
(författare)
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Femtosecond X-ray induced changes of the electronic and magnetic response of solids from electron redistribution
- 2019
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Resonant X-ray absorption, where an X-ray photon excites a core electron into an unoccupied valence state, is an essential process in many standard X-ray spectroscopies. With increasing X-ray intensity, the X-ray absorption strength is expected to become nonlinear. Here, we report the onset of such a nonlinearity in the resonant X-ray absorption of magnetic Co/Pd multilayers near the Co L-3 edge. The nonlinearity is directly observed through the change of the absorption spectrum, which is modified in less than 40 fs within 2 eV of its threshold. This is interpreted as a redistribution of valence electrons near the Fermi level. For our magnetic sample this also involves mixing of majority and minority spins, due to sample demagnetization. Our findings reveal that nonlinear X-ray responses of materials may already occur at relatively low intensities, where the macroscopic sample is not destroyed, providing insight into ultrafast charge and spin dynamics.
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| 35. |
- Holley, Concerta L., et al.
(författare)
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A Single Amino Acid Substitution in Elongation Factor G Can Confer Low-Level Gentamicin Resistance in Neisseria gonorrhoeae
- 2022
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Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 66:5
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Tidskriftsartikel (refereegranskat)abstract
- The continued emergence of Neisseria gonorrhoeae isolates which are resistant to first-line antibiotics has reinvigorated interest in alternative therapies such as expanded use of gentamicin (Gen). We hypothesized that expanded use of Gen promotes emergence of gonococci with clinical resistance to this aminoglycoside. To understand how decreased susceptibility of gonococci to Gen might develop, we selected spontaneous low-level Gen-resistant (GenR) mutants (Gen MIC = 32 μg/mL) of the Gen-susceptible strain FA19. Consequently, we identified a novel missense mutation in fusA, which encodes elongation factor G (EF-G), causing an alanine (A) to valine (V) substitution at amino acid position 563 in domain IV of EF-G; the mutant allele was termed fusA2. Transformation analysis showed that fusA2 could increase the Gen MIC by 4-fold. While possession of fusA2 did not impair either in vitro gonococcal growth or protein synthesis, it did result in a fitness defect during experimental infection of the lower genital tract in female mice. Through bioinformatic analysis of whole-genome sequences of 10,634 international gonococcal clinical isolates, other fusA alleles were frequently detected, but genetic studies revealed that they could not decrease Gen susceptibility in a similar manner to fusA2. In contrast to these diverse international fusA alleles, the fusA2-encoded A563V substitution was detected in only a single gonococcal clinical isolate. We hypothesize that the rare occurrence of fusA2 in N. gonorrhoeae clinical isolates is likely due to a fitness cost during infection, but compensatory mutations which alleviate this fitness cost could emerge and promote GenR in global strains.
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| 36. |
- Le Guyader, Loïc, et al.
(författare)
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State-resolved ultrafast charge and spin dynamics in [Co/Pd] multilayers
- 2022
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 120:3
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Tidskriftsartikel (refereegranskat)abstract
- We use transient absorption spectroscopy with circularly polarized x rays to detect laser-excited hole states below the Fermi level and compare their dynamics with that of unoccupied states above the Fermi level in ferromagnetic [Co/Pd] multilayers. While below the Fermi level, an instantaneous and significantly stronger demagnetization is observed, above the Fermi level, the demagnetization is delayed by 35 ± 10 fs. This provides a direct visualization of how ultrafast demagnetization proceeds via initial spin-flip scattering of laser-excited holes to the subsequent formation of spin waves.
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| 37. |
- Liu, Gang, et al.
(författare)
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Evaluating the reintroduction project of Przewalski's horse in China using genetic and pedigree data
- 2014
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Ingår i: Biological Conservation. - : Elsevier BV. - 0006-3207 .- 1873-2917. ; 171, s. 288-298
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Tidskriftsartikel (refereegranskat)abstract
- Przewalski's horse went extinct in the wild in the mid 1960s. Starting in 1985, individuals were brought from western zoos to two centers in China and breeding programs were initiated. With the increasing size of captive populations, two reintroduction projects were launched in the northwestern China in 2001 and 2010. Knowledge on genetic diversity in China's horse populations is limited, but would help improve the genetic management and assess the success of the reintroduction. Accordingly, one reintroduced and two captive populations were examined with 10 microsatellite loci together with pedigree data. The results showed higher level of diversity within the captive populations than the reintroduced population, indicating some alleles may have been lost during reintroduction. Genetic differentiation was detected among populations (F-ST = 0.09 +/- 0.05, Rhos(ST) = 0.05 +/- 0.02) and Bayesian clustering supported the presence of three subpopulations. The highest genetic differentiation was observed between the captive and reintroduced populations, and inbreeding coefficients were generally higher in the reintroduced population. Temporal estimates of both pedigree and microsatellite data showed a high, but decreasing level inbreeding. Through simulations, we estimated that the reintroduced population needs more than 100 individuals to retain approximately 90% of its current, already depauperate, genetic diversity. We have provided recommendations for the management program concerning introgressed genes from domestic horse and the number and origin of individuals for future reintroductions. (C) 2014 Elsevier Ltd. All rights reserved.
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| 38. |
- Margeridon-Thermet, S, et al.
(författare)
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Ultra-deep pyrosequencing of hepatitis B virus quasispecies from nucleoside and nucleotide reverse-transcriptase inhibitor (NRTI)-treated patients and NRTI-naive patients
- 2009
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Ingår i: Journal of Infectious Diseases. - : University of Chicago Press. - 0022-1899 .- 1537-6613. ; 199:9, s. 1275-1285
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Tidskriftsartikel (refereegranskat)abstract
- The dynamics of emerging nucleoside and nucleotide reverse-transcriptase inhibitor (NRTI) resistance in hepatitis B virus (HBV) are not well understood because standard dideoxynucleotide direct polymerase chain reaction (PCR) sequencing assays detect drug-resistance mutations only after they have become dominant. To obtain insight into NRTI resistance, we used a new sequencing technology to characterize the spectrum of low-prevalence NRTI-resistance mutations in HBV obtained from 20 plasma samples from 11 NRTI-treated patients and 17 plasma samples from 17 NRTI-naive patients, by using standard direct PCR sequencing and ultra-deep pyrosequencing (UDPS). UDPS detected drug-resistance mutations that were not detected by PCR in 10 samples from 5 NRTI-treated patients, including the lamivudine-resistance mutation V173L (in 5 samples), the entecavir-resistance mutations T184S (in 2 samples) and S202G (in 1 sample), the adefovir-resistance mutation N236T (in 1 sample), and the lamivudine and adefovir-resistance mutations V173L, L180M, A181T, and M204V (in 1 sample). G-to-A hypermutation mediated by the apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like family of cytidine deaminases was estimated to be present in 0.6% of reverse-transcriptase genes. Genotype A coinfection was detected by UDPS in each of 3 patients in whom genotype G virus was detected by direct PCR sequencing. UDPS detected low-prevalence HBV variants with NRTI-resistance mutations, G-to-A hypermutation, and low-level dual genotype infection with a sensitivity not previously possible.
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| 39. |
- Nielsen, Scott E., et al.
(författare)
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Environmental, biological and anthropogenic effects on grizzly bear body size : temporal and spatial considerations
- 2013
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Ingår i: BMC Ecology. - : Springer Science and Business Media LLC. - 1472-6785. ; 13, s. 31-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Individual body growth is controlled in large part by the spatial and temporal heterogeneity of, and competition for, resources. Grizzly bears (Ursus arctos L.) are an excellent species for studying the effects of resource heterogeneity and maternal effects (i.e. silver spoon) on life history traits such as body size because their habitats are highly variable in space and time. Here, we evaluated influences on body size of grizzly bears in Alberta, Canada by testing six factors that accounted for spatial and temporal heterogeneity in environments during maternal, natal and 'capture' (recent) environments. After accounting for intrinsic biological factors (age, sex), we examined how body size, measured in mass, length and body condition, was influenced by: (a) population density; (b) regional habitat productivity; (c) inter-annual variability in productivity (including silver spoon effects); (d) local habitat quality; (e) human footprint (disturbances); and (f) landscape change. Results: We found sex and age explained the most variance in body mass, condition and length (R-2 from 0.48-0.64). Inter-annual variability in climate the year before and of birth (silver spoon effects) had detectable effects on the three-body size metrics (R-2 from 0.04-0.07); both maternal (year before birth) and natal (year of birth) effects of precipitation and temperature were related with body size. Local heterogeneity in habitat quality also explained variance in body mass and condition (R-2 from 0.01-0.08), while annual rate of landscape change explained additional variance in body length (R-2 of 0.03). Human footprint and population density had no observed effect on body size. Conclusions: These results illustrated that body size patterns of grizzly bears, while largely affected by basic biological characteristics (age and sex), were also influenced by regional environmental gradients the year before, and of, the individual's birth thus illustrating silver spoon effects. The magnitude of the silver spoon effects was on par with the influence of contemporary regional habitat productivity, which showed that both temporal and spatial influences explain in part body size patterns in grizzly bears. Because smaller bears were found in colder and less-productive environments, we hypothesize that warming global temperatures may positively affect body mass of interior bears.
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| 40. |
- Northrup, Joseph M., et al.
(författare)
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Fine-scale genetic correlates to condition and migration in a wild cervid
- 2014
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Ingår i: Evolutionary Applications. - : Wiley. - 1752-4571. ; 7:8, s. 937-948
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Tidskriftsartikel (refereegranskat)abstract
- The relationship between genetic variation and phenotypic traits is fundamental to the study and management of natural populations. Such relationships often are investigated by assessing correlations between phenotypic traits and heterozygosity or genetic differentiation. Using an extensive data set compiled from free-ranging mule deer (Odocoileus hemionus), we combined genetic and ecological data to (i) examine correlations between genetic differentiation and migration timing, (ii) screen for mitochondrial haplotypes associated with migration timing, and (iii) test whether nuclear heterozygosity was associated with condition. Migration was related to genetic differentiation (more closely related individuals migrated closer in time) and mitochondrial haplogroup. Body fat was related to heterozygosity at two nuclear loci (with antagonistic patterns), one of which is situated near a known fat metabolism gene in mammals. Despite being focused on a widespread panmictic species, these findings revealed a link between genetic variation and important phenotypes at a fine scale. We hypothesize that these correlations are either the result of mixing refugial lineages or differential mitochondrial haplotypes influencing energetics. The maintenance of phenotypic diversity will be critical to enable the potential tracking of changing climatic conditions, and these correlates highlight the need to consider evolutionary mechanisms in management, even in widely distributed panmictic species.
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| 41. |
- Peart, Claire R., et al.
(författare)
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Determinants of genetic variation across eco-evolutionary scales in pinnipeds
- 2020
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Ingår i: Nature Ecology & Evolution. - : NATURE PUBLISHING GROUP. - 2397-334X. ; 4:8, s. 1095-1104
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Tidskriftsartikel (refereegranskat)abstract
- The effective size of a population (N-e), which determines its level of neutral variability, is a key evolutionary parameter. N-e can substantially depart from census sizes of present-day breeding populations (N-C) as a result of past demographic changes, variation in life-history traits and selection at linked sites. Using genome-wide data we estimated the long-term coalescent N-e for 17 pinniped species represented by 36 population samples (total n = 458 individuals). N-e estimates ranged from 8,936 to 91,178, were highly consistent within (sub)species and showed a strong positive correlation with N-C (R-adj(2) = 0.59; P = 0.0002). N-e/N-C ratios were low (mean, 0.31; median, 0.13) and co-varied strongly with demographic history and, to a lesser degree, with species' ecological and life-history variables such as breeding habitat. Residual variation in N-e/N-C, after controlling for past demographic fluctuations, contained information about recent population size changes during the Anthropocene. Specifically, species of conservation concern typically had positive residuals indicative of a smaller contemporary N-C than would be expected from their long-term N-e. This study highlights the value of comparative population genomic analyses for gauging the evolutionary processes governing genetic variation in natural populations, and provides a framework for identifying populations deserving closer conservation attention.
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| 42. |
- Pugh, Thomas A.M., et al.
(författare)
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Understanding the uncertainty in global forest carbon turnover
- 2020
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 17:15, s. 3961-3989
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Tidskriftsartikel (refereegranskat)abstract
- The length of time that carbon remains in forest biomass is one of the largest uncertainties in the global carbon cycle, with both recent historical baselines and future responses to environmental change poorly constrained by available observations. In the absence of large-scale observations, models used for global assessments tend to fall back on simplified assumptions of the turnover rates of biomass and soil carbon pools. In this study, the biomass carbon turnover times calculated by an ensemble of contemporary terrestrial biosphere models (TBMs) are analysed to assess their current capability to accurately estimate biomass carbon turnover times in forests and how these times are anticipated to change in the future. Modelled baseline 1985-2014 global average forest biomass turnover times vary from 12.2 to 23.5 years between TBMs. TBM differences in phenological processes, which control allocation to, and turnover rate of, leaves and fine roots, are as important as tree mortality with regard to explaining the variation in total turnover among TBMs. The different governing mechanisms exhibited by each TBM result in a wide range of plausible turnover time projections for the end of the century. Based on these simulations, it is not possible to draw robust conclusions regarding likely future changes in turnover time, and thus biomass change, for different regions. Both spatial and temporal uncertainty in turnover time are strongly linked to model assumptions concerning plant functional type distributions and their controls. Thirteen model-based hypotheses of controls on turnover time are identified, along with recommendations for pragmatic steps to test them using existing and novel observations. Efforts to resolve uncertainty in turnover time, and thus its impacts on the future evolution of biomass carbon stocks across the world's forests, will need to address both mortality and establishment components of forest demography, as well as allocation of carbon to woody versus non-woody biomass growth.
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| 43. |
- Rhee, SY, et al.
(författare)
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Spectrum of Atazanavir-Selected Protease Inhibitor-Resistance Mutations
- 2022
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Ingår i: Pathogens (Basel, Switzerland). - : MDPI AG. - 2076-0817. ; 11:5
-
Tidskriftsartikel (refereegranskat)abstract
- Ritonavir-boosted atazanavir is an option for second-line therapy in low- and middle-income countries (LMICs). We analyzed publicly available HIV-1 protease sequences from previously PI-naïve patients with virological failure (VF) following treatment with atazanavir. Overall, 1497 patient sequences were identified, including 740 reported in 27 published studies and 757 from datasets assembled for this analysis. A total of 63% of patients received boosted atazanavir. A total of 38% had non-subtype B viruses. A total of 264 (18%) sequences had a PI drug-resistance mutation (DRM) defined as having a Stanford HIV Drug Resistance Database mutation penalty score. Among sequences with a DRM, nine major DRMs had a prevalence >5%: I50L (34%), M46I (33%), V82A (22%), L90M (19%), I54V (16%), N88S (10%), M46L (8%), V32I (6%), and I84V (6%). Common accessory DRMs were L33F (21%), Q58E (16%), K20T (14%), G73S (12%), L10F (10%), F53L (10%), K43T (9%), and L24I (6%). A novel nonpolymorphic mutation, L89T occurred in 8.4% of non-subtype B, but in only 0.4% of subtype B sequences. The 264 sequences included 3 (1.1%) interpreted as causing high-level, 14 (5.3%) as causing intermediate, and 27 (10.2%) as causing low-level darunavir resistance. Atazanavir selects for nine major and eight accessory DRMs, and one novel nonpolymorphic mutation occurring primarily in non-B sequences. Atazanavir-selected mutations confer low-levels of darunavir cross resistance. Clinical studies, however, are required to determine the optimal boosted PI to use for second-line and potentially later line therapy in LMICs.
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| 44. |
- Sánchez-Busó, Leonor, et al.
(författare)
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A community-driven resource for genomic epidemiology and antimicrobial resistance prediction of Neisseria gonorrhoeae at Pathogenwatch
- 2021
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Ingår i: Genome Medicine. - : BioMed Central. - 1756-994X. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Antimicrobial-resistant (AMR) Neisseria gonorrhoeae is an urgent threat to public health, as strains resistant to at least one of the two last-line antibiotics used in empiric therapy of gonorrhoea, ceftriaxone and azithromycin, have spread internationally. Whole genome sequencing (WGS) data can be used to identify new AMR clones and transmission networks and inform the development of point-of-care tests for antimicrobial susceptibility, novel antimicrobials and vaccines. Community-driven tools that provide an easy access to and analysis of genomic and epidemiological data is the way forward for public health surveillance.METHODS: Here we present a public health-focussed scheme for genomic epidemiology of N. gonorrhoeae at Pathogenwatch ( https://pathogen.watch/ngonorrhoeae ). An international advisory group of experts in epidemiology, public health, genetics and genomics of N. gonorrhoeae was convened to inform on the utility of current and future analytics in the platform. We implement backwards compatibility with MLST, NG-MAST and NG-STAR typing schemes as well as an exhaustive library of genetic AMR determinants linked to a genotypic prediction of resistance to eight antibiotics. A collection of over 12,000 N. gonorrhoeae genome sequences from public archives has been quality-checked, assembled and made public together with available metadata for contextualization.RESULTS: AMR prediction from genome data revealed specificity values over 99% for azithromycin, ciprofloxacin and ceftriaxone and sensitivity values around 99% for benzylpenicillin and tetracycline. A case study using the Pathogenwatch collection of N. gonorrhoeae public genomes showed the global expansion of an azithromycin-resistant lineage carrying a mosaic mtr over at least the last 10 years, emphasising the power of Pathogenwatch to explore and evaluate genomic epidemiology questions of public health concern.CONCLUSIONS: The N. gonorrhoeae scheme in Pathogenwatch provides customised bioinformatic pipelines guided by expert opinion that can be adapted to public health agencies and departments with little expertise in bioinformatics and lower-resourced settings with internet connection but limited computational infrastructure. The advisory group will assess and identify ongoing public health needs in the field of gonorrhoea, particularly regarding gonococcal AMR, in order to further enhance utility with modified or new analytic methods.
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| 45. |
- Shafer, Aaron B. A., et al.
(författare)
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Bioinformatic processing of RAD-seq data dramatically impacts downstream population genetic inference
- 2017
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Ingår i: Methods in Ecology and Evolution. - 2041-210X. ; 8:8, s. 907-917
-
Tidskriftsartikel (refereegranskat)abstract
- 1. Restriction site-associated DNA sequencing (RAD-seq) provides high-resolution population genomic data at low cost, and has become an important component in ecological and evolutionary studies. As with all high-throughput technologies, analytic strategies require critical validation to ensure precise and unbiased interpretation. 2. To test the impact of bioinformatic data processing on downstream population genetic inferences, we analysed mammalian RAD-seq data (>100 individuals) with 312 combinations of methodology (de novo vs. mapping to references of increasing divergence) and filtering criteria (missing data, HWE, F-IS, coverage, mapping and genotype quality). In an effort to identify commonalities and biases in all pipelines, we computed summary statistics (nr. loci, nr. SNP, pi, Het(obs), F-IS, F-ST, N-e and m) and compared the results to independent null expectations (isolation-by-distance correlation, expected transition-to-transversion ratio T-s/T-v and Mendelian mismatch rates of known parent-offspring trios). 3. We observed large differences between reference-based and de novo approaches, the former generally calling more SNPs and reducing F-IS and T-s/T-v. Data completion levels showed little impact on most summary statistics, and FST estimates were robust across all pipelines. The site frequency spectrum was highly sensitive to the chosen approach as reflected in large variance of parameter estimates across demographic scenarios (single-population bottlenecks and isolation-with-migration model). Null expectations were best met by reference-based approaches, although contingent on the specific criteria. 4. We recommend that RAD-seq studies employ reference-based approaches to a closely related genome, and due to the high stochasticity associated with the pipeline advocate the use of multiple pipelines to ensure robust population genetic and demographic inferences.
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| 46. |
- Shafer, Aaron B. A., et al.
(författare)
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Cross-Species Application of SNP Chips is Not Suitable for Identifying Runs of Homozygosity
- 2016
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Ingår i: Journal of Heredity. - : Oxford University Press (OUP). - 0022-1503 .- 1465-7333. ; 107:2, s. 193-195
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Tidskriftsartikel (refereegranskat)abstract
- Cross-species application of single-nucleotide polymorphism (SNP) chips is a valid, relatively cost-effective alternative to the high-throughput sequencing methods generally required to obtain a genome-wide sampling of polymorphisms. Kharzinova et al. (2015) examined the applicability of SNP chips developed in domestic bovids (cattle and sheep) to a semi-wild cervid (reindeer). The ancestors of bovids and cervids diverged between 20 and 30 million years ago (Hassanin and Douzery 2003; Bibi et al. 2013). Empirical work has shown that for a SNP chip developed in a bovid and applied to a cervid species, approximately 50% genotype success with 1% of the loci being polymorphic is expected (Miller et al. 2012). The genotyping of Kharzinova et al. (2015) follows this pattern; however, these data are not appropriate for identifying runs of homozygosity (ROH) and can be problematic for estimating linkage disequilibrium (LD) and we caution readers in this regard.
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| 47. |
- Shafer, Aaron B. A., et al.
(författare)
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Forecasting Ecological Genomics : High-Tech Animal Instrumentation Meets High-Throughput Sequencing
- 2016
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Recent advancements in animal tracking technology and high-throughput sequencing are rapidly changing the questions and scope of research in the biological sciences. The integration of genomic data with high-tech animal instrumentation comes as a natural progression of traditional work in ecological genetics, and we provide a framework for linking the separate data streams from these technologies. Such a merger will elucidate the genetic basis of adaptive behaviors like migration and hibernation and advance our understanding of fundamental ecological and evolutionary processes such as pathogen transmission, population responses to environmental change, and communication in natural populations.
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| 48. |
- Shafer, Aaron B. A., et al.
(författare)
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Linking genotype, ecotype, and phenotype in an intensively managed large carnivore
- 2014
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Ingår i: Evolutionary Applications. - : Wiley. - 1752-4571. ; 7:2, s. 301-312
-
Tidskriftsartikel (refereegranskat)abstract
- Numerous factors influence fitness of free-ranging animals, yet often these are uncharacterized. We integrated GPS habitat use data and genetic profiling to determine their influence on fitness proxies (mass, length, and body condition) in a threatened population of grizzly bears (Ursus arctos) in Alberta, Canada. We detected distinct genetic and habitat use (ecotype) clusters, with individual cluster assignments, or genotype/ecotype, being correlated (Pearson r=0.34, P<0.01). Related individuals showed evidence of similar habitat use patterns, irrespective of geographic distance and sex. Fitness proxies were influenced by sex, age, and habitat use, and homozygosity had a positive effect on these proxies that could be indicative of outbreeding depression. We further documented over 300 translocations occurring in the province since the 1970s, often to areas with significantly different habitat. We argue this could be unintentionally causing the pattern of outbreeding, although the heterozygosity correlation may instead be explained by the energetic costs associated with larger body size. The observed patterns, together with the unprecedented human-mediated migrations, make understanding the link between genotype, ecotype, and phenotype and mechanisms behind the negative heterozygosity-fitness correlations critical for management and conservation of this species.
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| 49. |
- Shafer, Aaron B. A., et al.
(författare)
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Widespread evidence for incipient ecological speciation : a meta-analysis of isolation-by-ecology
- 2013
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Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 16:7, s. 940-950
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Forskningsöversikt (refereegranskat)abstract
- Ecologically mediated selection has increasingly become recognised as an important driver of speciation. The correlation between neutral genetic differentiation and environmental or phenotypic divergence among populations, to which we collectively refer to as isolation-by-ecology (IBE), is an indicator of ecological speciation. In a meta-analysis framework, we determined the strength and commonality of IBE in nature. On the basis of 106 studies, we calculated a mean effect size of IBE with and without controlling for spatial autocorrelation among populations. Effect sizes were 0.34 (95% CI 0.24-0.42) and 0.26 (95% CI 0.13-0.37), respectively, indicating that an average of 5% of the neutral genetic differentiation among populations was explained purely by ecological contrast. Importantly, spatial autocorrelation reduced IBE correlations for environmental variables, but not for phenotypes. Through simulation, we showed how the influence of isolation-by-distance and spatial autocorrelation of ecological variables can result in false positives or underestimated correlations if not accounted for in the IBE model. Collectively, this meta-analysis showed that ecologically induced genetic divergence is pervasive across time-scales and taxa, and largely independent of the choice of molecular marker. We discuss the importance of these results in the context of adaptation and ecological speciation and suggest future research avenues.
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| 50. |
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