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Sökning: WFRF:(Vogt Lars) > (2020-2023)

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1.
  • Aranda-Guillén, Maribel, et al. (författare)
  • A polygenic risk score to help discriminate primary adrenal insufficiency of different etiologies.
  • 2023
  • Ingår i: Journal of internal medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 294:1, s. 96-109
  • Tidskriftsartikel (refereegranskat)abstract
    • Autoimmune Addison's disease (AAD) is the most common cause of primary adrenal insufficiency (PAI). Despite its exceptionally high heritability, tools to estimate disease susceptibility in individual patients are lacking. We hypothesized that polygenic risk score (PRS) for AAD could help investigate PAI pathogenesis in pediatric patients.We here constructed and evaluated a PRS for AAD in 1223 seropositive cases and 4097 controls. To test its clinical utility, we reevaluated 18 pediatric patients, whose whole genome we also sequenced. We next explored the individual PRS in more than 120 seronegative patients with idiopathic PAI.The genetic susceptibility to AAD-quantified using PRS-was on average 1.5 standard deviations (SD) higher in patients compared with healthy controls (p<2e-16), and 1.2 SD higher in the young patients compared with the old (p=3e-4). Using the novel PRS, we searched for pediatric patients with strikingly low AAD susceptibility and identified cases of monogenic PAI, previously misdiagnosed as AAD. By stratifying seronegative adult patients by autoimmune comorbidities and disease duration we could delineate subgroups of PRS suggesting various disease etiologies.The PRS performed well for case-control differentiation and susceptibility estimation in individual patients. Remarkably, a PRS for AAD holds promise as a means to detect disease etiologies other than autoimmunity.
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2.
  • David, Romain, et al. (författare)
  • Converging on a Semantic Interoperability Framework for the European Data Space for Science, Research and Innovation (EOSC)
  • 2023
  • Konferensbidrag (refereegranskat)abstract
    • Semantic interoperability (SI) is at the heart of the FAIR principles and of the design of large scale cross disciplinary infrastructures. The European Open Science Cloud (EOSC) is a European-wide effort towards such an infrastructure, aiming to deepen the regional research collaboration and realising a shared data space for science, research and innovation. In this context, the research community’s voice is represented by the EOSC Association (EOSC-A) and a number of advisory groups with a broad range of representatives from different stakeholder organisations. The advisory group on metadata and data quality has formed a task force focusing on developing and implementing recommendations for SI (EOSC SI Task Force) with the ambition to converge on globally relevant and scalable SI solutions for EOSC. This paper provides context to SI in EOSC, the various components contributing to it, as well as some views on the socio-technical challenges to arriving at a consensus. In particular, the paper provides motivation for exploring the heterogeneity of SI solutions demonstrated across scientific communities and insight into the task force’s planned approach to conduct a survey to identify relevant components and structures. The paper is also an invitation to the global community to align and engage with the task force’s activities going forward.
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3.
  • Hendriks, Kasper P., et al. (författare)
  • Global Brassicaceae phylogeny based on filtering of 1,000-gene dataset
  • 2023
  • Ingår i: Current Biology. - : Elsevier. - 0960-9822 .- 1879-0445. ; 33:19, s. 4052-4068
  • Tidskriftsartikel (refereegranskat)abstract
    • The mustard family (Brassicaceae) is a scientifically and economically important family, containing the model plant Arabidopsis thaliana and numerous crop species that feed billions worldwide. Despite its relevance, most phylogenetic trees of the family are incompletely sampled and often contain poorly supported branches. Here, we present the most complete Brassicaceae genus-level family phylogenies to date (Bras-sicaceae Tree of Life or BrassiToL) based on nuclear (1,081 genes, 319 of the 349 genera; 57 of the 58 tribes) and plastome (60 genes, 265 genera; all tribes) data. We found cytonuclear discordance between the two, which is likely a result of rampant hybridization among closely and more distantly related lineages. To eval-uate the impact of such hybridization on the nuclear phylogeny reconstruction, we performed five different gene sampling routines, which increasingly removed putatively paralog genes. Our cleaned subset of 297 genes revealed high support for the tribes, whereas support for the main lineages (supertribes) was moder-ate. Calibration based on the 20 most clock-like nuclear genes suggests a late Eocene to late Oligocene origin of the family. Finally, our results strongly support a recently published new family classification, dividing the family into two subfamilies (one with five supertribes), together representing 58 tribes. This includes five recently described or re-established tribes, including Arabidopsideae, a monogeneric tribe accommodating Arabidopsis without any close relatives. With a worldwide community of thousands of researchers working on Brassicaceae and its diverse members, our new genus-level family phylogeny will be an indispensable tool for studies on biodiversity and plant biology.
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4.
  • Kurek, Magdalena, et al. (författare)
  • Spermatogonia Loss Correlates with LAMA 1 Expression in Human Prepubertal Testes Stored for Fertility Preservation
  • 2021
  • Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 10:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Fertility preservation for male childhood cancer survivors not yet capable of producing mature spermatozoa, relies on experimental approaches such as testicular explant culture. Although the first steps in somatic maturation can be observed in human testicular explant cultures, germ cell depletion is a common obstacle. Hence, understanding the spermatogonial stem cell (SSC) niche environment and in particular, specific components such as the seminiferous basement membrane (BM) will allow progression of testicular explant cultures. Here, we revealed that the seminiferous BM is established from 6 weeks post conception with the expression of laminin alpha 1 (LAMA 1) and type IV collagen, which persist as key components throughout development. With prepubertal testicular explant culture we found that seminiferous LAMA 1 expression is disrupted and depleted with culture time correlating with germ cell loss. These findings highlight the importance of LAMA 1 for the human SSC niche and its sensitivity to culture conditions.
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5.
  • Peng, Guotao, et al. (författare)
  • Nitric oxide-dependent biodegradation of graphene oxide reduces inflammation in the gastrointestinal tract
  • 2020
  • Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 12:32, s. 16730-16737
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding the biological fate of graphene-based materials such as graphene oxide (GO) is crucial to assess adverse effects following intentional or inadvertent exposure. Here we provide first evidence of biodegradation of GO in the gastrointestinal tract using zebrafish as a model. Raman mapping was deployed to assess biodegradation. The degradation was blocked upon knockdown ofnos2aencoding the inducible nitric oxide synthase (iNOS) or by pharmacological inhibition of NOS usingl-NAME, demonstrating that the process was nitric oxide (NO)-dependent. NO-dependent degradation of GO was further confirmedin vitroby combining a superoxide-generating system, xanthine/xanthine oxidase (X/XO), with an NO donor (PAPA NONOate), or by simultaneously producing superoxide and NO by decomposition of SIN-1. Finally, by using the transgenic strainTg(mpx:eGFP) to visualize the movement of neutrophils, we could show that inhibition of the degradation of GO resulted in increased neutrophil infiltration into the gastrointestinal tract, indicative of inflammation.
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6.
  • Sunnerhagen, Torgny, et al. (författare)
  • Biofilm formation on endovascular aneurysm repair (EVAR) grafts– a proof of concept in vitro model
  • 2023
  • Ingår i: Clinical Microbiology and Infection. - 1469-0691. ; 29:12, s. 1-1600
  • 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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