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- 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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- Axfors, Cathrine, et al.
(författare)
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Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
- 2021
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Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
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Forskningsöversikt (refereegranskat)abstract
- Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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- Caban, Kelvin, et al.
(författare)
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A conformational switch in initiation factor 2 controls the fidelity of translation initiation in bacteria
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Initiation factor (IF) 2 controls the fidelity of translation initiation by selectively increasing the rate of 50S ribosomal subunit joining to 30S initiation complexes (ICs) that carry an N-formyl-methionyl-tRNA (fMet-tRNA(fMet)). Previous studies suggest that rapid 50S subunit joining involves a GTP- and fMet-tRNA(fMet)-dependent "activation" of IF2, but a lack of data on the structure and conformational dynamics of 30S IC-bound IF2 has precluded a mechanistic understanding of this process. Here, using an IF2-tRNA single-molecule fluorescence resonance energy transfer signal, we directly observe the conformational switch that is associated with IF2 activation within 30S ICs that lack IF3. Based on these results, we propose a model of IF2 activation that reveals how GTP, fMet-tRNA(fMet), and specific structural elements of IF2 drive and regulate this conformational switch. Notably, we find that domain III of IF2 plays a pivotal, allosteric, role in IF2 activation, suggesting that this domain can be targeted for the development of novel antibiotics.
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- De Tarafder, Arindam
(författare)
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Adaptive Evolution of the Bacterial Translation Machinery
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The process of protein synthesis via translation is of paramount importance for the existence of life on Earth. The bacterial translation machinery has embraced more than 3.5 billion years of molecular evolution to adapt and function efficiently under the provided physiological conditions. This thesis dwells on the intricacies of the adaptive evolution, which the massively complex translation machinery has undergone to function optimally in diverse conditions and habitats. In Paper I, we used elongation factor Tu (EF-Tu) as a model system to follow the evolution of ribosome specificity in translation factors. For that, we have biochemically characterized two sequence-reconstructed ancestral EF-Tu variants for their specificities towards two unrelated extant bacterial ribosomes, mesophilic Escherichia coli and thermophilic Thermus thermophilus. Our fast kinetics-based biochemical analysis hints at the ‘generalist’ ancestry of modern EF-Tu proteins. In Paper II, we have reconstituted an in vitro translation system of the psychrotolerant bacteria Pseudoalteromonas haloplanktis to quantitatively characterize the steps of translation elongation. Our results demonstrate similar kinetics of peptide bond formation in psychrotolerant P. haloplanktis and mesophilic E. coli. In contrast, P. haloplanktis ribosome exhibits much slower rates of EF-G-catalyzed tRNA translocation than E. coli. Comparison and swapping of the EF-Gs and tRNAs between the two in vitro translation systems indicate that the slow translocation is likely an inherent property of the P. haloplanktis ribosome. Furthermore, our results demonstrate the varied extent of antibiotic inhibition on the P. haloplanktis minimal translation system, particularly when targeting processes related to translocation and peptide bond formation, compared to E. coli. In Paper III, we used ribosomes from bacterial species of diverse habitats to show that the ribosomes in vitro can maintain their catalytic activity beyond the survival temperature cutoff of the native host. Moreover, our results indicate that the thermostability of essential translation factors, EF-Tu and EF-G, dictates the upper limit of reaction temperature for translation elongation. Finally, we demonstrate that ribosomes from a psychrophile, mesophile, and thermophile can function in a vast temperature range of 10-70 °C, provided the translation factors remain structurally and functionally stable. Our results highlight the thermal versatility of the ribosome and reiterate the early emergence of a thermostable ribosomal core in the primordial RNA world.The outcome of this thesis will unveil some of the intricate mechanisms underlying the evolution of bacterial translation machinery. This knowledge may open up new research avenues regarding the emergence and diversification of bacteria and the development of new therapeutic strategies.
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