| 1. |
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| 2. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 5. |
- 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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| 6. |
- Burrascano, S., et al.
(författare)
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Where are we now with European forest multi-taxon biodiversity and where can we head to?
- 2023
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Ingår i: Biological Conservation. - 0006-3207. ; 284
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Tidskriftsartikel (refereegranskat)abstract
- The European biodiversity and forest strategies rely on forest sustainable management (SFM) to conserve forest biodiversity. However, current sustainability assessments hardly account for direct biodiversity indicators. We focused on forest multi-taxon biodiversity to: i) gather and map the existing information; ii) identify knowledge and research gaps; iii) discuss its research potential. We established a research network to fit data on species, standing trees, lying deadwood and sampling unit description from 34 local datasets across 3591 sampling units. A total of 8724 species were represented, with the share of common and rare species varying across taxonomic classes: some included many species with several rare ones (e.g., Insecta); others (e.g., Bryopsida) were repre-sented by few common species. Tree-related structural attributes were sampled in a subset of sampling units (2889; 2356; 2309 and 1388 respectively for diameter, height, deadwood and microhabitats). Overall, multi-taxon studies are biased towards mature forests and may underrepresent the species related to other develop-mental phases. European forest compositional categories were all represented, but beech forests were over-represented as compared to thermophilous and boreal forests. Most sampling units (94%) were referred to a habitat type of conservation concern. Existing information may support European conservation and SFM stra-tegies in: (i) methodological harmonization and coordinated monitoring; (ii) definition and testing of SFM in-dicators and thresholds; (iii) data-driven assessment of the effects of environmental and management drivers on multi-taxon forest biological and functional diversity, (iv) multi-scale forest monitoring integrating in-situ and remotely sensed information.
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| 8. |
- Shepherd, L., et al.
(författare)
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Infection-related and -unrelated malignancies, HIV and the aging population
- 2016
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Ingår i: HIV Medicine. - : Wiley. - 1464-2662 .- 1468-1293. ; 17:8, s. 590-600
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: HIV-positive people have increased risk of infection-related malignancies (IRMs) and infection-unrelated malignancies (IURMs). The aim of the study was to determine the impact of aging on future IRM and IURM incidence. Methods: People enrolled in EuroSIDA and followed from the latest of the first visit or 1 January 2001 until the last visit or death were included in the study. Poisson regression was used to investigate the impact of aging on the incidence of IRMs and IURMs, adjusting for demographic, clinical and laboratory confounders. Linear exponential smoothing models forecasted future incidence. Results: A total of 15 648 people contributed 95 033 person-years of follow-up, of whom 610 developed 643 malignancies [IRMs: 388 (60%); IURMs: 255 (40%)]. After adjustment, a higher IRM incidence was associated with a lower CD4 count [adjusted incidence rate ratio (aIRR) CD4 count < 200 cells/μL: 3.77; 95% confidence interval (CI) 2.59, 5.51; compared with ≥ 500 cells/μL], independent of age, while a CD4 count < 200 cells/μL was associated with IURMs in people aged < 50 years only (aIRR: 2.51; 95% CI 1.40–4.54). Smoking was associated with IURMs (aIRR: 1.75; 95% CI 1.23, 2.49) compared with never smokers in people aged ≥ 50 years only, and not with IRMs. The incidences of both IURMs and IRMs increased with older age. It was projected that the incidence of IRMs would decrease by 29% over a 5-year period from 3.1 (95% CI 1.5–5.9) per 1000 person-years in 2011, whereas the IURM incidence would increase by 44% from 4.1 (95% CI 2.2–7.2) per 1000 person-years over the same period. Conclusions: Demographic and HIV-related risk factors for IURMs (aging and smoking) and IRMs (immunodeficiency and ongoing viral replication) differ markedly and the contribution from IURMs relative to IRMs will continue to increase as a result of aging of the HIV-infected population, high smoking and lung cancer prevalence and a low prevalence of untreated HIV infection. These findings suggest the need for targeted preventive measures and evaluation of the cost−benefit of screening for IURMs in HIV-infected populations.
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| 9. |
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| 10. |
- Ackley, K., et al.
(författare)
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Observational constraints on the optical and near-infrared emission from the neutron star-black hole binary merger candidate S190814bv
- 2020
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 643
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Tidskriftsartikel (refereegranskat)abstract
- Context. Gravitational wave (GW) astronomy has rapidly reached maturity, becoming a fundamental observing window for modern astrophysics. The coalescences of a few tens of black hole (BH) binaries have been detected, while the number of events possibly including a neutron star (NS) is still limited to a few. On 2019 August 14, the LIGO and Virgo interferometers detected a high-significance event labelled S190814bv. A preliminary analysis of the GW data suggests that the event was likely due to the merger of a compact binary system formed by a BH and a NS.Aims. In this paper, we present our extensive search campaign aimed at uncovering the potential optical and near infrared electromagnetic counterpart of S190814bv. We found no convincing electromagnetic counterpart in our data. We therefore use our non-detection to place limits on the properties of the putative outflows that could have been produced by the binary during and after the merger.Methods. Thanks to the three-detector observation of S190814bv, and given the characteristics of the signal, the LIGO and Virgo Collaborations delivered a relatively narrow localisation in low latency - a 50% (90%) credible area of 5 deg(2) (23 deg(2)) - despite the relatively large distance of 26752 Mpc. ElectromagNetic counterparts of GRAvitational wave sources at the VEry Large Telescope collaboration members carried out an intensive multi-epoch, multi-instrument observational campaign to identify the possible optical and near infrared counterpart of the event. In addition, the ATLAS, GOTO, GRAWITA-VST, Pan-STARRS, and VINROUGE projects also carried out a search on this event. In this paper, we describe the combined observational campaign of these groups.Results. Our observations allow us to place limits on the presence of any counterpart and discuss the implications for the kilonova (KN), which was possibly generated by this NS-BH merger, and for the strategy of future searches. The typical depth of our wide-field observations, which cover most of the projected sky localisation probability (up to 99.8%, depending on the night and filter considered), is r similar to 22 (resp. K similar to 21) in the optical (resp. near infrared). We reach deeper limits in a subset of our galaxy-targeted observations, which cover a total similar to 50% of the galaxy-mass-weighted localisation probability. Altogether, our observations allow us to exclude a KN with large ejecta mass M greater than or similar to 0.1 M-circle dot to a high (> 90%) confidence, and we can exclude much smaller masses in a sub-sample of our observations. This disfavours the tidal disruption of the neutron star during the merger.Conclusions. Despite the sensitive instruments involved in the campaign, given the distance of S190814bv, we could not reach sufficiently deep limits to constrain a KN comparable in luminosity to AT 2017gfo on a large fraction of the localisation probability. This suggests that future (likely common) events at a few hundred megaparsecs will be detected only by large facilities with both a high sensitivity and large field of view. Galaxy-targeted observations can reach the needed depth over a relevant portion of the localisation probability with a smaller investment of resources, but the number of galaxies to be targeted in order to get a fairly complete coverage is large, even in the case of a localisation as good as that of this event.
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| 11. |
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| 15. |
- Peters, S., et al.
(författare)
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Reconditioning the Neurogenic Niche of Adult Non-human Primates by Antisense Oligonucleotide-Mediated Attenuation of TGFβ Signaling
- 2021
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Ingår i: Neurotherapeutics. - : Springer Nature. - 1933-7213 .- 1878-7479. ; 18:3, s. 1963-1979
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Tidskriftsartikel (refereegranskat)abstract
- Adult neurogenesis is a target for brain rejuvenation as well as regeneration in aging and disease. Numerous approaches showed efficacy to elevate neurogenesis in rodents, yet translation into therapies has not been achieved. Here, we introduce a novel human TGFβ-RII (Transforming Growth Factor—Receptor Type II) specific LNA-antisense oligonucleotide (“locked nucleotide acid”—“NVP-13”), which reduces TGFβ-RII expression and downstream receptor signaling in human neuronal precursor cells (ReNcell CX® cells) in vitro. After we injected cynomolgus non-human primates repeatedly i.th. with NVP-13 in a preclinical regulatory 13-week GLP-toxicity program, we could specifically downregulate TGFβ-RII mRNA and protein in vivo. Subsequently, we observed a dose-dependent upregulation of the neurogenic niche activity within the hippocampus and subventricular zone: human neural progenitor cells showed significantly (up to threefold over control) enhanced differentiation and cell numbers. NVP-13 treatment modulated canonical and non-canonical TGFβ pathways, such as MAPK and PI3K, as well as key transcription factors and epigenetic factors involved in stem cell maintenance, such as MEF2A and pFoxO3. The latter are also dysregulated in clinical neurodegeneration, such as amyotrophic lateral sclerosis. Here, we provide for the first time in vitro and in vivo evidence for a novel translatable approach to treat neurodegenerative disorders by modulating neurogenesis.
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| 16. |
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| 17. |
- Mikkelsen, T N, et al.
(författare)
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Experimental design of multifactor climate change experiments with elevated CO2, warming and drought: the CLIMAITE project
- 2008
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Ingår i: Functional Ecology. - : Wiley. - 1365-2435 .- 0269-8463. ; 22:1, s. 185-195
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Tidskriftsartikel (refereegranskat)abstract
- Recent findings indicate that the interactions among CO2, temperature and water can be substantial, and that the combined effects on the biological systems of several factors may not be predicted from experiments with one or a few factors. Therefore realistic multifactorial experiments involving a larger set of main factors are needed. We describe a new Danish climate change-related field scale experiment, CLIMAITE, in a heath/grassland ecosystem. CLIMAITE is a full factorial combination of elevated CO2, elevated temperature and prolonged summer drought. The manipulations are intended to mimic anticipated major environmental changes at the site by year 2075 as closely as possible. The impacts on ecosystem processes and functioning (at ecophysiological levels, through responses by individuals and communities to ecosystem-level responses) are investigated simultaneously. The increase of [CO2] closely corresponds with the scenarios for year 2075, while the warming treatment is at the lower end of the predictions and seems to be the most difficult treatment to increase without unwanted side effects on the other variables. The drought treatment follows predictions of increased frequency of drought periods in summer. The combination of the treatments does not create new unwanted side effects on the treatments relative to the treatments alone.
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| 18. |
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| 19. |
- Collet, M. O., et al.
(författare)
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Functional and cognitive rehabilitation interventions during intensive care admission: A protocol for a systematic integrative review
- 2023
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 67:5, s. 670-4
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundLong-term cognitive impairment occurs in up to 60% of intensive care unit (ICU) survivors. Early use of functional and cognitive rehabilitation interventions, while patients are still in ICU, may reduce cognitive decline. We aim to describe the functional and cognitive interventions used during the ICU stay, the healthcare professionals providing interventions, and the potential impact on functional and cognitive rehabilitation. MethodIn this integrative systematic review, we will include empirical qualitative, quantitative, mixed- and multiple-methods studies assessing the use of functional and cognitive rehabilitation provided in ICU. We will identify studies in relevant electronic databases from 2012 to 2022, which will be screened for eligibility by at least two reviewers. Literature reported as narrative reviews and editorials will be excluded. We will assess the impact of interventions evaluating a cognitive and functional function, quality of life, and all-cause mortality at 6-12 months after ICU discharge. The Revised Cochrane risk-of-bias Tool will be used for assessing risk of bias in clinical trials. For observational studies, we will use the National Institutes of Health Quality Assessment tool for Observational Cohort and Cross-Sectional Studies. Furthermore, we will use the critical appraisal skills programme for qualitative studies and the mixed methods appraisal tool for mixed methods studies. We will construct four matrices, including results describing which ICU patients and healthcare professionals were engaged in rehabilitation, which interventions were included in early rehabilitation in ICU, the potential impact on patient outcomes of rehabilitation interventions provided in ICU and a narrative synthesis of themes. A summary of the main results will be reported using modified GRADE methodology. ImpactThis integrative review will inform the feasibility randomised clinical trial testing the development of a complex intervention targeting functional and cognitive rehabilitation for patients in ICU.
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| 20. |
- Ekström, P., et al.
(författare)
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Neural elements in the pineal complex of the frog, rana esculenta, II : Gaba-immunoreactive neurons and FMRFamide-immunoreactive efferent axons
- 1990
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Ingår i: Visual Neuroscience. - 0952-5238. ; 4:5, s. 399-412
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Tidskriftsartikel (refereegranskat)abstract
- The photosensory pineal complex of anurans comprises an extracranial part, the frontal organ, and an intracranial part, the pineal organ proper. Although the pineal organ functions mainly as a luminosity detector, the frontal organ may monitor the relative proportions of short and intermediate/long wavelengths in the ambient illumination. The major pathway of information processing in the pineal and frontal organs is the photoreceptor to ganglion cell synapse. It is not known whether interneurons form part of the neural circuitry. In the present study, we demonstrate GABA-immunoreactive (GABA-IR) neurons in the pineal and frontal organs ofthe frog, Rana esculenta. No GABA-IR axons were observed in the pineal nerve between the frontal and pineal organs, or in the pineal tract that connects the pineal complex with the brain. The GABA-IR neurons differed in morphology from centrally projecting neurons visualized by retrograde labeling with horseradish peroxidase. Thus, we suggest that the GABA-IR neurons in the pineal and frontal organs represent local interneurons. Axons of central origin, immunoreactive with a sensitive antiserum against the tetrapeptide Phe-Met-Phe-Arg-NH2 (FMRFamide), were observed in the intracranial portion of the photosensory pineal organ. The immunoreactive axons enter the caudal pole of the pineal organ via the posterior commissure. The largest density of axons was observed in the caudal part, while fewer axons were detected in the rostral portion. The uneven distribution of the FMRFamide-immunoreactive axons may be related to the distribution of different types of intrapineal neurons. FMRFamide-immunoreactive varicose axons were observed in the extracranial frontal organ. A central innervation of the pineal organ, previously known exclusively from amniotes, is probably not per se linked with the evolutionary transition of the pineal organ from a directly photosensory organ to a neuroendocrine organ. It could rather represent a centrifugal input to a sensory system which has been retained when the directly sensory functions have changed, during phylogeny, to neuroendocrine functions.
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| 21. |
- Levan, A. J., et al.
(författare)
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The Environment of the Binary Neutron Star Merger GW170817
- 2017
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 848:2
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Tidskriftsartikel (refereegranskat)abstract
- We present Hubble Space Telescope (HST) and Chandra imaging, combined with Very Large Telescope MUSE integral field spectroscopy of the counterpart and host galaxy of the first binary neutron star merger detected via gravitational-wave emission by LIGO and Virgo, GW170817. The host galaxy, NGC 4993, is an S0 galaxy at z - 0.009783. There is evidence for large, face-on spiral shells in continuum imaging, and edge-on spiral features visible in nebular emission lines. This suggests that NGC 4993 has undergone a relatively recent (less than or similar to 1 Gyr) dry merger. This merger may provide the fuel for a weak active nucleus seen in Chandra imaging. At the location of the counterpart, HST imaging implies there is no globular or young stellar cluster, with a limit of a few thousand solar masses for any young system. The population in the vicinity is predominantly old with less than or similar to 1% of any light arising from a population with ages <500 Myr. Both the host galaxy properties and those of the transient location are consistent with the distributions seen for short-duration gamma-ray bursts, although the source position lies well within the effective radius (r(e) similar to 3 kpc), providing an r(e)-normalized offset that is closer than similar to 90% of short GRBs. For the long delay time implied by the stellar population, this suggests that the kick velocity was significantly less than the galaxy escape velocity. We do not see any narrow host galaxy interstellar medium features within the counterpart spectrum, implying low extinction, and that the binary may lie in front of the bulk of the host galaxy.
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| 22. |
- Oddsson, Asmundur, et al.
(författare)
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Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. To explore genetic causes of recessive lethality, we searched for sequence variants with deficit of homozygosity among 1.52 million individuals from six European populations. In this study, we identified 25 genes harboring protein-altering sequence variants with a strong deficit of homozygosity (10% or less of predicted homozygotes). Sequence variants in 12 of the genes cause Mendelian disease under a recessive mode of inheritance, two under a dominant mode, but variants in the remaining 11 have not been reported to cause disease. Sequence variants with a strong deficit of homozygosity are over-represented among genes essential for growth of human cell lines and genes orthologous to mouse genes known to affect viability. The function of these genes gives insight into the genetics of intrauterine lethality. We also identified 1077 genes with homozygous predicted loss-of-function genotypes not previously described, bringing the total set of genes completely knocked out in humans to 4785.
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| 23. |
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| 24. |
- Sirivåg, K, et al.
(författare)
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Physical exercise augmented cognitive behaviour therapy for older adults with generalised anxiety disorder (PEXACOG) : Study protocol and feasibility results from a randomised controlled trial
- 2018
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Konferensbidrag (refereegranskat)abstract
- Background. Generalised anxiety disorder (GAD) is prevalent among older adults. These patients exhibit impaired response to cognitive behaviour therapy (CBT), and physical exercise has been recommended as a potential add-on intervention to improve efficacy. The current study is a randomised clinical trial that will compare CBT augmented with physical exercise, or CBT combined with attention placebo, and the current study assessing the feasibility of testing procedures and the experimental combined treatment measures.Methods. 4 participants were included in the feasibility study, and feasibility was assessed trough completion and attendance rates of testing and treatment sessions. Primary outcome measures were remission as assessed by an independent clinical rater using the Anxiety Disorders Interview Schedule for DSM-IV, and by symptom reduction on Penn State Worry Questionnaire. Manipulation check was assessed by physical tests of change in aerobic capacity and strength. Participants were measured on clinical, biological, physiological and neuropsychological tests at pre-, interim and post-treatment.Results. Completed treatment protocol for the RCT will be presented. 3 of 4 participants completed the full protocol including testing and the experimental augmented treatment. Participants completed 100% and 80% of CBT and physical exercise content, respectively. The three completers had large improvements on primary outcome and on manipulation checks.Conclusion. The testing procedures and experimental augmented treatment appear to be feasible. The preliminary findings indicate that this combined intervention can be efficacious.
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| 27. |
- Lauridsen, T. K., et al.
(författare)
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Echocardiographic findings predict in-hospital and 1-year mortality in left-sided native valve Staphylococcus aureus endocarditis: Analysis from the international collaboration on endocarditis-prospective echo cohort study
- 2015
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Ingår i: Circulation Cardiovascular Imaging. - 1941-9651. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Staphylococcus aureus left-sided native valve infective endocarditis (LNVIE) has higher complication and mortality rates compared with endocarditis from other pathogens. Whether echocardiographic variables can predict prognosis in S aureus LNVIE is unknown. Methods and Results: Consecutive patients with LNVIE, enrolled between January 2000 and September 2006, in the International Collaboration on Endocarditis were identified. Subjects without S aureus IE were matched to those with S aureus IE by the propensity of having S aureus. Survival differences were determined using log-rank significance tests. Independent echocardiographic predictors of mortality were identified using Cox-proportional hazards models that included inverse probability of treatment weighting and surgery as a time-dependent covariate. Of 727 subjects with LNVIE and 1-year follow-up, 202 had S aureus IE. One-year survival rates were significantly lower for patients with S aureus IE overall (57% S aureus IE versus 80% non-S aureus IE; P<0.001) and in the propensity-matched cohort (59% S aureus IE versus 68% non-S aureus IE; P<0.05). Intracardiac abscess (hazard ratio, 2.93; 95% confidence interval, 1.52-5.40; P<0.001) and left ventricular ejection fraction <40% (odds ratio, 3.01; 95% confidence interval, 1.35-6.04; P=0.004) were the only independent echocardiographic predictors of in-hospital mortality in S aureus LNVIE. Valve perforation (hazard ratio, 2.16; 95% confidence interval, 1.21-3.68; P=0.006) and intracardiac abscess (hazard ratio, 2.25; 95% confidence interval, 1.26-3.78; P=0.004) were the only independent predictors of 1-year mortality. Conclusions: S aureus is an independent predictor of 1-year mortality in subjects with LNVIE. In S aureus LNVIE, intracardiac abscess and left ventricular ejection fraction <40% independently predicted in-hospital mortality and intracardiac abscess and valve perforation independently predicted 1-year mortality. © 2015 American Heart Association, Inc.
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| 28. |
- Miranda, Alex, et al.
(författare)
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Cancer stemness, intratumoral heterogeneity, and immune response across cancers
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:18, s. 9020-9029
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Tidskriftsartikel (refereegranskat)abstract
- Regulatory programs that control the function of stem cells are active in cancer and confer properties that promote progression and therapy resistance. However, the impact of a stem cell-like tumor phenotype ("stemness") on the immunological properties of cancer has not been systematically explored. Using gene-expression-based metrics, we evaluated the association of stemness with immune cell infiltration and genomic, transcriptomic, and clinical parameters across 21 solid cancers. We found pervasive negative associations between cancer stemness and anticancer immunity. This occurred despite high stemness cancers exhibiting increased mutation load, cancer-testis antigen expression, and intratumoral heterogeneity. Stemness was also strongly associated with cellintrinsic suppression of endogenous retroviruses and type I IFN signaling, and increased expression of multiple therapeutically accessible immunosuppressive pathways. Thus, stemness is not only a fundamental process in cancer progression but may provide a mechanistic link between antigenicity, intratumoral heterogeneity, and immune suppression across cancers.
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| 29. |
- Rønn, SG, et al.
(författare)
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Suppressor of cytokine signalling-3 expression inhibits cytokine-mediated destruction of primary mouse and rat pancreatic islets and delays allograft rejection
- 2008
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 51:10, s. 1873-1882
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis The pro-inflammatory cytokines IL-1 and IFN gamma are critical molecules in immune-mediated beta cell destruction leading to type 1 diabetes mellitus. Suppressor of cytokine signalling (SOCS)-3 inhibits the cytokine-mediated destruction of insulinoma-1 cells. Here we investigate the effect of SOCS3 in primary rodent beta cells and diabetic animal models. Methods Using mice with beta cell-specific Socs3 expression and a Socs3-encoding adenovirus construct, we characterised the protective effect of SOCS3 in mouse and rat islets subjected to cytokine stimulation. In transplantation studies of NOD mice and alloxan-treated mice the survival of Socs3 transgenic islets was investigated. Results Socs3 transgenic islets showed significant resistance to cytokine-induced apoptosis and impaired insulin release. Neither glucose-stimulated insulin release, insulin content or glucose oxidation were affected by SOCS3. Rat islet cultures transduced with Socs3-adenovirus displayed reduced cytokine-induced nitric oxide and apoptosis associated with inhibition of the IL-1-induced nuclear factor-kappa B and mitogen-activated protein kinase (MAPK) pathways. Transplanted Socs3 transgenic islets were not protected in diabetic NOD mice, but showed a prolonged graft survival when transplanted into diabetic allogenic BALB/c mice. Conclusions/interpretation SOCS3 inhibits IL-1-induced signalling through the nuclear factor-kappa B and MAPK pathways and apoptosis induced by cytokines in primary beta cells. Moreover, Socs3 transgenic islets are protected in an allogenic transplantation model. SOCS3 may represent a target for pharmacological or genetic engineering in islet transplantation for treatment of type 1 diabetes mellitus.
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| 30. |
- Siemens, N, et al.
(författare)
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Increased cytotoxicity and streptolysin O activity in group G streptococcal strains causing invasive tissue infections
- 2015
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5, s. 16945-
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus dysgalactiae subsp. equisimilis (SDSE) has emerged as an important cause of severe skin and soft tissue infections, but little is known of the pathogenic mechanisms underlying tissue pathology. Patient samples and a collection of invasive and non-invasive group G SDSE strains (n = 69) were analyzed with respect to virulence factor expression and cytotoxic or inflammatory effects on human cells and 3D skin tissue models. SDSE strains efficiently infected the 3D-skin model and severe tissue pathology, inflammatory responses and altered production of host structural framework proteins associated with epithelial barrier integrity were evident already at 8 hours post-infection. Invasive strains were significantly more cytotoxic towards keratinocytes and expressed higher Streptokinase and Streptolysin O (SLO) activities, as compared to non-invasive strains. The opposite was true for Streptolysin S (SLS). Fractionation and proteomic analysis of the cytotoxic fractions implicated SLO as a factor likely contributing to the keratinocyte cytotoxicity and tissue pathology. Analyses of patient tissue biopsies revealed massive bacterial load, high expression of slo, as well as immune cell infiltration and pro-inflammatory markers. Our findings suggest the contribution of SLO to epithelial cytotoxicity and tissue pathology in SDSE tissue infections.
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| 31. |
- Starch-Jensen, T, et al.
(författare)
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Radiographic graft changes following maxillary sinus floor augmentation with autogenous bone compared with composite grafts : a one-year single-blind randomized controlled trial
- 2024
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Ingår i: International Journal of Oral and Maxillofacial Surgery. - : Elsevier. - 0901-5027 .- 1399-0020.
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Tidskriftsartikel (refereegranskat)abstract
- This study evaluated radiographic graft changes following maxillary sinus floor augmentation with (A) autogenous bone, (B) 1:1 autogenous bone and deproteinized porcine bone mineral, or (C) 1:1 autogenous bone and biphasic bone graft material. Sixty patients were randomly allocated to groups A, B, and C (20 in each). CBCT scans were obtained at enrolment, after surgery (T1), after prosthetic rehabilitation (T2), and 1 year after implant loading (T3). Significant decreases in graft volume (3D) and graft height (2D) from T1 to T3 were observed in all groups (P < 0.05). However, at T2 and T3, graft volume was significantly higher in group B than in groups A and C (P < 0.05), and graft height was significantly higher in group B than in group A (P < 0.05). Bone density increased significantly from T1 to T2 in all groups (P < 0.001). However, bone density was significantly higher in group B than in groups A and C, at T2 and T3 (P < 0.05). No significant correlation between graft volume or height and implant protrusion length or residual bone height was found. In conclusion, 1:1 autogenous bone and porcine bone resulted in significantly higher graft volume, height, and bone density when compared with autogenous bone or a 1:1 ratio of autogenous bone and biphasic bone. However the higher graft volume, height, and bone density did not appear to lead to improved outcomes at 1 year of functional loading when compared to the other groups.
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| 32. |
- Wunderling, Nico, 1992-, et al.
(författare)
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Climate tipping point interactions and cascades : a review
- 2024
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Ingår i: Earth System Dynamics. - 2190-4979 .- 2190-4987. ; 15:1, s. 41-74
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Forskningsöversikt (refereegranskat)abstract
- Climate tipping elements are large-scale subsystems of the Earth that may transgress critical thresholds (tipping points) under ongoing global warming, with substantial impacts on the biosphere and human societies. Frequently studied examples of such tipping elements include the Greenland Ice Sheet, the Atlantic Meridional Overturning Circulation (AMOC), permafrost, monsoon systems, and the Amazon rainforest. While recent scientific efforts have improved our knowledge about individual tipping elements, the interactions between them are less well understood. Also, the potential of individual tipping events to induce additional tipping elsewhere or stabilize other tipping elements is largely unknown. Here, we map out the current state of the literature on the interactions between climate tipping elements and review the influences between them. To do so, we gathered evidence from model simulations, observations, and conceptual understanding, as well as examples of paleoclimate reconstructions where multi-component or spatially propagating transitions were potentially at play. While uncertainties are large, we find indications that many of the interactions between tipping elements are destabilizing. Therefore, we conclude that tipping elements should not only be studied in isolation, but also more emphasis has to be put on potential interactions. This means that tipping cascades cannot be ruled out on centennial to millennial timescales at global warming levels between 1.5 and 2.0 ∘C or on shorter timescales if global warming surpassed 2.0 ∘C. At these higher levels of global warming, tipping cascades may then include fast tipping elements such as the AMOC or the Amazon rainforest. To address crucial knowledge gaps in tipping element interactions, we propose four strategies combining observation-based approaches, Earth system modeling expertise, computational advances, and expert knowledge.
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