| 1. |
- Ball, Sarah, et al.
(författare)
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Genetic and demographic vulnerability of adder populations : Results of a genetic study in mainland Britain
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:4
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Tidskriftsartikel (refereegranskat)abstract
- Genetic factors are often overlooked in conservation planning, despite their importance in small isolated populations. We used mitochondrial and microsatellite markers to investigate population genetics of the adder (Vipera berus) in southern Britain, where numbers are declining. We found no evidence for loss of heterozygosity in any of the populations studied. Genetic diversity was comparable across sites, in line with published levels for mainland Europe. However, further analysis revealed a striking level of relatedness. Genetic networks constructed from inferred first degree relationships suggested a high proportion of individuals to be related at a level equivalent to that of half-siblings, with rare inferred full-sib dyads. These patterns of relatedness can be attributed to the high philopatry and low vagility of adders, which creates high local relatedness, in combination with the polyandrous breeding system in the adder, which may offset the risk of inbreeding in closed populations. We suggest that reliance on standard genetic indicators of inbreeding and diversity may underestimate demographic and genetic factors that make adder populations vulnerable to extirpation. We stress the importance of an integrated genetic and demographic approach in the conservation of adders, and other taxa of similar ecology.
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| 2. |
- Barack, Leor, et al.
(författare)
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Black holes, gravitational waves and fundamental physics : a roadmap
- 2019
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Ingår i: Classical and quantum gravity. - : IOP Publishing. - 0264-9381 .- 1361-6382. ; 36:14
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Forskningsöversikt (refereegranskat)abstract
- The grand challenges of contemporary fundamental physics dark matter, dark energy, vacuum energy, inflation and early universe cosmology, singularities and the hierarchy problem all involve gravity as a key component. And of all gravitational phenomena, black holes stand out in their elegant simplicity, while harbouring some of the most remarkable predictions of General Relativity: event horizons, singularities and ergoregions. The hitherto invisible landscape of the gravitational Universe is being unveiled before our eyes: the historical direct detection of gravitational waves by the LIGO-Virgo collaboration marks the dawn of a new era of scientific exploration. Gravitational-wave astronomy will allow us to test models of black hole formation, growth and evolution, as well as models of gravitational-wave generation and propagation. It will provide evidence for event horizons and ergoregions, test the theory of General Relativity itself, and may reveal the existence of new fundamental fields. The synthesis of these results has the potential to radically reshape our understanding of the cosmos and of the laws of Nature. The purpose of this work is to present a concise, yet comprehensive overview of the state of the art in the relevant fields of research, summarize important open problems, and lay out a roadmap for future progress. This write-up is an initiative taken within the framework of the European Action on 'Black holes, Gravitational waves and Fundamental Physics'.
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| 3. |
- Hess, Timo, et al.
(författare)
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Dissecting the genetic heterogeneity of gastric cancer
- 2023
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 92
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO.
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| 4. |
- Hjelm, Claus-Göran, et al.
(författare)
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Standards with future relevance for European Social Science data infrastructure / Needs, Key Areas, Rules & Best Practices in Metadata Standard selection and usage : DELIVERABLE D7.2: D7.3 - Data without Boundaries (DwB) WORK PACKAGE 7 - Standards Development
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Support for searching and locating OS microdata at NSIs is by far not as developed and coordinated at a European level as for research data at DAs. No structured metadata base exist that present national OS microdata from the NSIs at a European and international level, even if there are some degree of integration via Eurostat/European Statistical System, (ESS)1, by which datasets from different countries are integrated through gathering data from common European Surveys coordinated by Eurostat/ESS. This report is to identify and to discuss such subjects and questions about “future needs”, “best practice” and “open issues” as related topics within the programmatic frame of WP7 on “Standards development”. The report integrates the former separated deliverable DwB D7.2 and DwB D7.3 to achieve most possible coherence and integration in answering leading questions in the field and tackling respective work package tasks. Thus DwB D7.2/3 emphasizes the need for standards development from different points of view, and results from the work in T7.2, T7.3, T7.4 and T7.5, which is detailed in the following. The audiences for this report are the statistical institutes and government agencies that would like to facilitate transnational discovery and access to official microdata.
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| 5. |
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| 6. |
- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 7. |
- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 8. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 9. |
- Sarneel, Judith M., et al.
(författare)
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Reading tea leaves worldwide : decoupled drivers of initial litter decomposition mass-loss rate and stabilization
- 2024
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Ingår i: Ecology Letters. - : John Wiley & Sons. - 1461-023X .- 1461-0248. ; 27:5
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Tidskriftsartikel (refereegranskat)abstract
- The breakdown of plant material fuels soil functioning and biodiversity. Currently, process understanding of global decomposition patterns and the drivers of such patterns are hampered by the lack of coherent large-scale datasets. We buried 36,000 individual litterbags (tea bags) worldwide and found an overall negative correlation between initial mass-loss rates and stabilization factors of plant-derived carbon, using the Tea Bag Index (TBI). The stabilization factor quantifies the degree to which easy-to-degrade components accumulate during early-stage decomposition (e.g. by environmental limitations). However, agriculture and an interaction between moisture and temperature led to a decoupling between initial mass-loss rates and stabilization, notably in colder locations. Using TBI improved mass-loss estimates of natural litter compared to models that ignored stabilization. Ignoring the transformation of dead plant material to more recalcitrant substances during early-stage decomposition, and the environmental control of this transformation, could overestimate carbon losses during early decomposition in carbon cycle models.
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| 10. |
- Sunnerhagen, Torgny, et al.
(författare)
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Biofilm formation on endovascular aneurysm repair (EVAR) grafts– a proof of concept in vitro model
- 2023
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Ingår i: Clinical Microbiology and Infection. - 1469-0691. ; 29:12, s. 1-1600
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesAn endovascular aneurysm repair (EVAR) graft is a catheter-implanted vascular prosthesis and is the preferred treatment for patients with aortic aneurysm. If an EVAR graft becomes the focus of infection, the treatment possibilities are limited as it is technically difficult to remove the graft to obtain source control. This study examines whether Pseudomonas aeruginosa and Staphylococcus aureus form biofilm on EVAR prostheses.MethodsEVAR graft sections were exposed to bacteria at 102 or 108 colony forming units (CFU)/ml in lysogeny broth and Krebs-Ringer at 37°C, bacterial biofilm formation was evaluated by scanning electron microscopy (SEM) and counting CFU on the graft sections following antibiotic exposure at x10 minimal inhibitory concentration (MIC). Bacteria were tested for tolerance to benzyl penicillin, tobramycin and ciprofloxacin.ResultsBacterial exposure for 15 minutes established biofilms on all prosthesis fragments (6/6 replicates). After 4 hours, bacteria were firmly attached to the EVAR prostheses and resisted washing. After 18 to 24 hours the median CFU/g of EVAR graft reached 5.2 x 108 (1.15 x 108 – 1.1 x 109) for S. aureus and 9.1 x 107 (3.5 x 107 – 6.25 x 108) for P. aeruginosa. SEM showed bacterial attachment to the graft pieces. There was a time-dependent development of tolerance with approximately 20 (tobramycin), 560 (benzyl penicillin), and 600 (ciprofloxacin) times more S. aureus surviving antibiotic exposure in 24 compared to 0 hours old biofilm. Five (tobramycin) and 170 times (ciprofloxacin) more P. aeruginosa survived antibiotic exposure in 24 compared to 0 hours old biofilms.ConclusionsOur results show that bacteria can rapidly adhere to and subsequently form antibiotic tolerant biofilms on EVAR graft material in concentrations equivalent to levels seen in transient bacteremia in vivo. Potentially, the system can be used for identifying optimal treatment combinations for infected EVAR prosthesis.
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