| 1. |
- Folkersen, Lasse, et al.
(författare)
-
Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- 2020
-
Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
-
Tidskriftsartikel (refereegranskat)abstract
- Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
|
|
| 2. |
- Gómez-Martínez, Daniela, et al.
(författare)
-
Phenotypic and transcriptomic acclimation of the green microalga Raphidocelis subcapitata to high environmental levels of the herbicide diflufenican
- 2023
-
Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 875
-
Tidskriftsartikel (refereegranskat)abstract
- Herbicide pollution poses a worldwide threat to plants and freshwater ecosystems. However, the understanding of how organisms develop tolerance to these chemicals and the associated trade-off expenses are largely unknown. This study aims to investigate the physiological and transcriptional mechanisms underlying the acclimation of the green microalgal model species Raphidocelis subcapitata (Selenastraceae) towards the herbicide diflufenican, and the fitness costs associated with tolerance development. Algae were exposed for 12 weeks (corresponding to 100 generations) to diflufenican at the two environmental concentrations 10 and 310 ng/L. The monitoring of growth, pigment composition, and photosynthetic performance throughout the experiment revealed an initial dose-dependent stress phase (week 1) with an EC50 of 397 ng/L, followed by a time-dependent recovery phase during weeks 2 to 4. After week 4, R. subcapitata was acclimated to diflufenican exposure with a similar growth rate, content of carotenoids, and photosynthetic performance as the unexposed control algae. This acclimation state of the algae was explored in terms of tolerance acquisition, changes in the fatty acids composition, diflufenican removal rate, cell size, and changes in mRNA gene expression profile, revealing potential fitness costs associated with acclimation, such as up-regulation of genes related to cell division, structure, morphology, and reduction of cell size. Overall, this study demonstrates that R. subcapitata can quickly acclimate to environmental but toxic levels of diflufenican; however, the acclimation is associated with trade-off expenses that result in smaller cell size.
|
|
| 3. |
- Karlsson, Joakim, et al.
(författare)
-
Molecular profiling of driver events in metastatic uveal melanoma
- 2020
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Metastatic uveal melanoma is less well understood than its primary counterpart, has a distinct biology compared to skin melanoma, and lacks effective treatments. Here we genomically profile metastatic tumors and infiltrating lymphocytes. BAP1 alterations are overrepresented and found in 29/32 of cases. Reintroducing a functional BAP1 allele into a deficient patient-derived cell line, reveals a broad shift towards a transcriptomic subtype previously associated with better prognosis of the primary disease. One outlier tumor has ahigh mutational burden associated with UV-damage. CDKN2A deletions also occur, which are rarely present in primaries. A focused knockdown screen is used to investigate overexpressed genesassociated withcopy number gains. Tumor-infiltrating lymphocytes are in several cases found tumor-reactive, but expression of the immune checkpoint receptors TIM-3, TIGIT and LAG3 is also abundant. This study represents the largest whole-genome analysis of uveal melanoma to date, and presents an updated view of the metastatic disease. © 2020, The Author(s).
|
|
| 4. |
- Nilsson, R. Henrik, 1976, et al.
(författare)
-
How, not if, is the question mycologists should be asking about DNA-based typification
- 2023
-
Ingår i: MycoKeys. - : Pensoft Publishers. - 1314-4057 .- 1314-4049. ; :96, s. 143-157
-
Tidskriftsartikel (refereegranskat)abstract
- Fungal metabarcoding of substrates such as soil, wood, and water is uncovering an unprecedented number of fungal species that do not seem to produce tangible morphological structures and that defy our best attempts at cultivation, thus falling outside the scope of the International Code of Nomenclature for algae, fungi, and plants. The present study uses the new, ninth release of the species hypotheses of the UNITE database to show that species discovery through environmental sequencing vastly outpaces traditional, Sanger sequencing-based efforts in a strongly increasing trend over the last five years. Our findings chal-lenge the present stance of some in the mycological community - that the current situation is satisfactory and that no change is needed to "the code" - and suggest that we should be discussing not whether to allow DNA-based descriptions (typifications) of species and by extension higher ranks of fungi, but what the precise requirements for such DNA-based typifications should be. We submit a tentative list of such criteria for further discussion. The present authors hope for a revitalized and deepened discussion on DNA-based typification, because to us it seems harmful and counter-productive to intentionally deny the overwhelming majority of extant fungi a formal standing under the International Code of Nomenclature for algae, fungi, and plants.
|
|
| 5. |
- Abarenkov, Kessy, et al.
(författare)
-
The curse of the uncultured fungus
- 2022
-
Ingår i: MycoKeys. - 1314-4057 .- 1314-4049. ; 86, s. 177-194
-
Tidskriftsartikel (refereegranskat)abstract
- The international DNA sequence databases abound in fungal sequences not annotated beyond the kingdom level, typically bearing names such as “uncultured fungus”. These sequences beget low-resolution mycological results and invite further deposition of similarly poorly annotated entries. What do these sequences represent? This study uses a 767,918-sequence corpus of public full-length fungal ITS sequences to estimate what proportion of the 95,055 “uncultured fungus” sequences that represent truly unidentifiable fungal taxa – and what proportion of them that would have been straightforward to annotate to some more meaningful taxonomic level at the time of sequence deposition. Our results suggest that more than 70% of these sequences would have been trivial to identify to at least the order/family level at the time of sequence deposition, hinting that factors other than poor availability of relevant reference sequences explain the low-resolution names. We speculate that researchers’ perceived lack of time and lack of insight into the ramifications of this problem are the main explanations for the low-resolution names. We were surprised to find that more than a fifth of these sequences seem to have been deposited by mycologists rather than researchers unfamiliar with the consequences of poorly annotated fungal sequences in molecular repositories. The proportion of these needlessly poorly annotated sequences does not decline over time, suggesting that this problem must not be left unchecked.
|
|
| 6. |
- Abarenkov, Kessy, et al.
(författare)
-
The UNITE database for molecular identification and taxonomic communication of fungi and other eukaryotes: sequences, taxa and classifications reconsidered
- 2024
-
Ingår i: Nucleic Acids Research. - 0305-1048 .- 1362-4962. ; 52:D1, s. D791-D797
-
Tidskriftsartikel (refereegranskat)abstract
- UNITE (https://unite.ut.ee) is a web-based database and sequence management environment for molecular identification of eukaryotes. It targets the nuclear ribosomal internal transcribed spacer (ITS) region and offers nearly 10 million such sequences for reference. These are clustered into similar to 2.4M species hypotheses (SHs), each assigned a unique digital object identifier (DOI) to promote unambiguous referencing across studies. UNITE users have contributed over 600 000 third-party sequence annotations, which are shared with a range of databases and other community resources. Recent improvements facilitate the detection of cross-kingdom biological associations and the integration of undescribed groups of organisms into everyday biological pursuits. Serving as a digital twin for eukaryotic biodiversity and communities worldwide, the latest release of UNITE offers improved avenues for biodiversity discovery, precise taxonomic communication and integration of biological knowledge across platforms. Graphical Abstract
|
|
| 7. |
- Abrego, Nerea, et al.
(författare)
-
Airborne DNA reveals predictable spatial and seasonal dynamics of fungi
- 2024
-
Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 631, s. 835-842
-
Tidskriftsartikel (refereegranskat)abstract
- Fungi are among the most diverse and ecologically important kingdoms in life. However, the distributional ranges of fungi remain largely unknown as do the ecological mechanisms that shape their distributions1,2. To provide an integrated view of the spatial and seasonal dynamics of fungi, we implemented a globally distributed standardized aerial sampling of fungal spores3. The vast majority of operational taxonomic units were detected within only one climatic zone, and the spatiotemporal patterns of species richness and community composition were mostly explained by annual mean air temperature. Tropical regions hosted the highest fungal diversity except for lichenized, ericoid mycorrhizal and ectomycorrhizal fungi, which reached their peak diversity in temperate regions. The sensitivity in climatic responses was associated with phylogenetic relatedness, suggesting that large-scale distributions of some fungal groups are partially constrained by their ancestral niche. There was a strong phylogenetic signal in seasonal sensitivity, suggesting that some groups of fungi have retained their ancestral trait of sporulating for only a short period. Overall, our results show that the hyperdiverse kingdom of fungi follows globally highly predictable spatial and temporal dynamics, with seasonality in both species richness and community composition increasing with latitude. Our study reports patterns resembling those described for other major groups of organisms, thus making a major contribution to the long-standing debate on whether organisms with a microbial lifestyle follow the global biodiversity paradigms known for macroorganisms4,5.
|
|
| 8. |
- Durkin, Louisa, et al.
(författare)
-
When mycologists describe new species, not all relevant information is provided (clearly enough).
- 2020
-
Ingår i: MycoKeys. - 1314-4049. ; 72, s. 109-128
-
Tidskriftsartikel (refereegranskat)abstract
- Taxonomic mycology struggles with what seems to be a perpetual shortage of resources. Logically, fungal taxonomists should therefore leverage every opportunity to highlight and visualize the importance of taxonomic work, the usefulness of taxonomic data far beyond taxonomy, and the integrative and collaborative nature of modern taxonomy at large. Is mycology really doing that, though? In this study, we went through ten years' worth (2009-2018) of species descriptions of extant fungal taxa - 1,097 studies describing at most ten new species - in five major mycological journals plus one plant journal. We estimated the frequency at which a range of key words, illustrations, and concepts related to ecology, geography, taxonomy, molecular data, and data availability were provided with the descriptions. We also considered a range of science-demographical aspects such as gender bias and the rejuvenation of taxonomy and taxonomists as well as public availability of the results. Our results show that the target audience of fungal species descriptions appears to be other fungal taxonomists, because many aspects of the new species were presented only implicitly, if at all. Although many of the parameters we estimated show a gradual, and in some cases marked, change for the better over time, they still paint a somewhat bleak picture of mycological taxonomy as a male-dominated field where the wants and needs of an extended target audience are often not understood or even considered. This study hopes to leave a mark on the way fungal species are described by putting the focus on ways in which fungal taxonomy can better anticipate the end users of species descriptions - be they mycologists, other researchers, the public at large, or even algorithms. In the end, fungal taxonomy, too, is likely to benefit from such measures.
|
|
| 9. |
- Eriksson, Martin, 1970, et al.
(författare)
-
Triclosan changes community composition and selects for specific bacterial taxa in marine periphyton biofilms in low nanomolar concentrations
- 2020
-
Ingår i: Ecotoxicology. - : Springer Science and Business Media LLC. - 0963-9292 .- 1573-3017. ; 29:7, s. 1083-1094
-
Tidskriftsartikel (refereegranskat)abstract
- The antibacterial agent Triclosan (TCS) is a ubiquitous environmental contaminant due to its widespread use. Sensitivity to TCS varies substantially among eu- and pro-karyotic species and its risk for the marine environment remains to be better elucidated. In particular, the effects that TCS causes on marine microbial communities are largely unknown. In this study we therefore used 16S amplicon rDNA sequencing to investigate TCS effects on the bacterial composition in marine periphyton communities that developed under long-term exposure to different TCS concentrations. Exposure to TCS resulted in clear changes in bacterial composition already at concentrations of 1 to 3.16 nM. We conclude that TCS affects the structure of the bacterial part of periphyton communities at concentrations that actually occur in the marine environment. Sensitive taxa, whose abundance decreased significantly with increasing TCS concentrations, include the Rhodobiaceae and Rhodobacteraceae families of Alphaproteobacteria, and unidentified members of the Candidate division Parcubacteria. Tolerant taxa, whose abundance increased significantly with higher TCS concentrations, include the families Erythrobacteraceae (Alphaproteobacteria), Flavobacteriaceae (Bacteroidetes), Bdellovibrionaceae (Deltaproteobacteria), several families of Gammaproteobacteria, and members of the Candidate phylum Gracilibacteria. Our results demonstrate the variability of TCS sensitivity among bacteria, and that TCS can change marine bacterial composition at concentrations that have been detected in the marine environment.
|
|
| 10. |
- Jacobsson, Amanda, et al.
(författare)
-
”Ambulanssjukvården behöver genomgripande förändringar”
- 2021
-
Ingår i: Dagens Medicin. - : Dagens Medicin. - 1402-1943. ; :2021-06-23
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Debattörer från Ambulance health research network vill se en nationell ledningsstruktur, ökad evidens för vården, akademisk kompetens i ledningsfunktioner samt en nationell utbildnings- och kompetensstandard.
|
|
