| 1. |
- Gustafsson, Lena, et al.
(författare)
-
Rapid ecological response and intensified knowledge accumulation following a north European mega-fire
- 2019
-
Ingår i: Scandinavian Journal of Forest Research. - : Informa UK Limited. - 0282-7581 .- 1651-1891. ; 34:4, s. 234-253
-
Forskningsöversikt (refereegranskat)abstract
- Deepened knowledge on response of biota and ecological processes following fire is essential for a future with warmer climate and more disturbances. In 2014 the first mega-fire (13,100 ha) for at least a century in Scandinavia hit south-central Sweden, in a production forest landscape shaped by clearcutting forestry. Ecological dynamics is followed in >20 projects from universities, authorities and citizen science initiatives, rapidly accumulating substantial amounts of data. We outline projects and summarize their results during the first four years, demonstrating a rapid succession of fungi, lichens, vascular plants, birds, mammals, ticks, butterflies, beetles, and drastically altered carbon dynamics. We characterize forest operations including regeneration measures and point to patterns in pest and pathogen infestations. 8,000 ha is set aside for natural succession, with the rest harvested and managed for forest production, offering excellent opportunities for studies on salvage logging effects, already evident for birds. We demonstrate a strong regrowth of deciduous trees, and the protected part will in some decades likely develop into the largest deciduous-dominated area in boreal north Europe outside Russia. Continued studies of biodiversity and ecological processes are urgent for this unique area.
|
|
| 2. |
- Oddsson, Asmundur, et al.
(författare)
-
Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality
- 2023
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
-
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.
|
|
| 3. |
- Apelgren, Peter, et al.
(författare)
-
Skin Grafting on 3D Bioprinted Cartilage Constructs In Vivo
- 2018
-
Ingår i: Plastic and Reconstructive Surgery-Global Open. - : Ovid Technologies (Wolters Kluwer Health). - 2169-7574. ; 6:9
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Three-dimensional (3D) bioprinting of cartilage is a promising new technique. To produce, for example, an auricle with good shape, the printed cartilage needs to be covered with skin that can grow on the surface of the construct. Our primary question was to analyze if an integrated 3D bioprinted cartilage structure is a tissue that can serve as a bed for a full-thickness skin graft. Methods: 3D bioprinted constructs (10x10x1.2mm) were printed using nanofibrillated cellulose/alginate bioink mixed with mesenchymal stem cells and adult chondrocytes and implanted subcutaneously in 21 nude mice. Results: After 45 days, a full-thickness skin allograft was transplanted onto the constructs and the grafted construct again enclosed subcutaneously. Group 1 was sacrificed on day 60, whereas group 2, instead, had their skin-bearing construct uncovered on day 60 and were sacrificed on day 75 and the explants were analyzed morphologically. The skin transplants integrated well with the 3D bioprinted constructs. A tight connection between the fibrous, vascularized capsule surrounding the 3D bioprinted constructs and the skin graft were observed. The skin grafts survived the uncovering and exposure to the environment. Conclusions: A 3D bioprinted cartilage that has been allowed to integrate in vivo is a sufficient base for a full-thickness skin graft. This finding accentuates the clinical potential of 3D bioprinting for reconstructive purposes.
|
|
| 4. |
- Aunes-Jansson, Maria, et al.
(författare)
-
Decrease of the atrial fibrillatory rate, increased organization of the atrial rhythm and termination of atrial fibrillation by AZD7009
- 2013
-
Ingår i: Journal of Electrocardiology. - : Elsevier BV. - 1532-8430 .- 0022-0736. ; 46:1, s. 29-35
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The atrial fibrillatory rate (APR), on AZD7009 as compared to placebo, was investigated as a potential biomarker for electrophysiological effect in early antiarrhythmic drug development. Methods: Patients with permanent AF received infusions of AZD7009 and placebo in an exploratory two-way, single-blind, randomized cross-over study. The ECG was continuously recorded, and following QRST cancellation the APR, its standard deviation (SD), the exponential decay and the atrial electrogram amplitude were determined as 3-min averages. Results: The mean APR rapidly decreased by 43% from baseline (394 +/- 38 to 225 +/- 61 fibrillations/min, p = 0.0003) on AZD7009, but not on placebo. The SD of the AFR and the exponential decay decreased in parallel. In 2 of 8 patients, termination of AF occurred after the APR had decreased by 58% and 53%, respectively. Conclusions: The APR may potentially serve as a biomarker of electrophysiological effects in early evaluation of rhythm control agents. (C) 2013 Elsevier Inc. All rights reserved.
|
|
| 5. |
|
|
| 6. |
- Burkill, Sarah, et al.
(författare)
-
The DQB1* 03:02 Genotype and Treatment for Pain in People With and Without Multiple Sclerosis
- 2020
-
Ingår i: Frontiers in Neurology. - : Frontiers. - 1664-2295. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Murine models have demonstrated that the major histocompatibility complex (MHC) is associated with pain-like behavior in peripheral nerve injury, however, the same association has not been shown when considering injury to the central nervous system (CNS), which more closely mimics the damage to the CNS experienced by MS patients. Previous research has indicated the DQB1*03:02 allele of the class II HLA genes as being associated with development of neuropathic pain in persons undergoing inguinal hernia surgery or with lumbar spinal disk herniation. Whether this HLA allele plays a part in susceptibility to pain, has not, as far as we are aware, been previously investigated. This study utilizes information on DQB1*03:02 alleles as part of the EIMS, GEMS, and IMSE studies in Sweden. It also uses register data for 3,877 MS patients, and 4,548 matched comparators without MS, to assess whether the DQB1*03:02 allele is associated with prescribed pain medication use, and whether associations with this genotype differ depending on MS status. Our results showed no association between the DQB1*03:02 genotype and pain medication in MS patients, with an adjusted odds ratio (OR) of 1.02 (95% CI 0.85-1.24). In contrast, there was a statistically significant association of low magnitude in individuals without MS [adjusted OR 1.18 (95% CI 1.03-1.35)], which provides support for HLA influence on susceptibility to pain in the general population. Additionally, the effect of zygosity was evident for the non-MS cohort, but not among MS patients, suggesting the DQB1*03:02 allele effect is modified by the presence of MS.
|
|
| 7. |
- Bådagård, Henrik, et al.
(författare)
-
Negative predictors of shunt surgery outcome in normal pressure hydrocephalus
- 2020
-
Ingår i: Acta Neurologica Scandinavica. - : Wiley. - 0001-6314 .- 1600-0404. ; 141:3, s. 219-225
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectivesThe prevalence of idiopathic normal pressure hydrocephalus (iNPH) and vascular comorbidity increases with age. It has not been clarified if high age and vascular disease are negative predictors of shunt surgery outcome in patients with iNPH. The aim of this study was to investigate the impact of high age and vascular comorbidity on outcome after shunt surgery in patients with iNPH.MethodsAll 332 patients with iNPH who were treated with shunts between 2011 and 2015 at a single centre were consecutively included. Hellström iNPH scale, without the neuropsychological tests, was calculated preoperatively and at follow‐up 12 months after shunt surgery. Outcome was defined as the difference between the post‐operative and preoperative iNPH scale scores. A multivariable model was used to investigate the predictive effects of age and vascular comorbidity on shunt surgery outcome.ResultsIn a multivariable analysis of covariance (ANCOVA) with post‐operative outcome as the dependent variable, increasing age (years, B = −0.63, P < .001) and history of ischaemic stroke (B = −10.06, P = .0038) were negative predictors of shunt surgery outcome after controlling for waiting time for surgery, symptom severity at preoperative control, presence of diabetes mellitus, hypertension, hyperlipidaemia, history of myocardial infarction, duration of symptoms and shunt complications.ConclusionsHigh age and established cerebrovascular disease are associated with less favourable outcome after shunt surgery in patients with iNPH.
|
|
| 8. |
- Engdahl, Elin, et al.
(författare)
-
Increased Serological Response Against Human Herpesvirus 6A Is Associated With Risk for Multiple Sclerosis
- 2019
-
Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Human herpesvirus (HHV)-6A or HHV-6B involvement in multiple sclerosis (MS) etiology has remained controversial mainly due to the lack of serological methods that can distinguish the two viruses. A novel multiplex serological assay measuring IgG reactivity against the immediate-early protein 1 from HHV-6A (IE1A) and HHV-6B (IE1B) was used in a MS cohort (8,742 persons with MS and 7,215 matched controls), and a pre-MS cohort (478 individuals and 476 matched controls) to investigate this further. The IgG response against IE1A was positively associated with MS (OR = 1.55, p = 9 × 10-22), and increased risk of future MS (OR = 2.22, p = 2 × 10-5). An interaction was observed between IE1A and Epstein-Barr virus (EBV) antibody responses for MS risk (attributable proportion = 0.24, p = 6 × 10-6). In contrast, the IgG response against IE1B was negatively associated with MS (OR = 0.74, p = 6 × 10-11). The association did not differ between MS subtypes or vary with severity of disease. The genetic control of HHV-6A/B antibody responses were located to the Human Leukocyte Antigen (HLA) region and the strongest association for IE1A was the DRB1*13:01-DQA1*01:03-DQB1*06:03 haplotype while the main association for IE1B was DRB1*13:02-DQA1*01:02-DQB1*06:04. In conclusion a role for HHV-6A in MS etiology is supported by an increased serological response against HHV-6A IE1 protein, an interaction with EBV, and an association to HLA genes.
|
|
| 9. |
- Hedström, Anna Karin, et al.
(författare)
-
Association between exposure to combustion-related air pollution and multiple sclerosis risk
- 2023
-
Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 52:3, s. 703-714
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Smoking and occupational pulmonary irritants contribute to multiple sclerosis (MS) development. We aimed to study the association between ambient air pollution and MS risk and potential interaction with the human leukocyte antigen (HLA)-DRB1*15:01 allele.Methods: Exposure to combustion-related air pollution was estimated as outdoor levels of nitrogen oxides (NOx) at the participants’ residence locations, by spatially resolved dispersion modelling for the years 1990–18. Using two population-based case-control studies (6635 cases, 8880 controls), NOx levels were associated with MS risk by calculating odds ratios (OR) with 95% confidence intervals (CI) using logistic regression models. Interaction between high NOx levels and the HLA-DRB1*15:01 allele regarding MS risk was calculated by the attributable proportion due to interaction (AP). In addition, a register study was performed comprising all MS cases in Sweden who had received their diagnosis between 1993 and 2018 (n = 22 173), with 10 controls per case randomly selected from the National Population register.Results: Residential air pollution was associated with MS risk. NOx levels (3-year average) exceeding the 90th percentile (24.6 µg/m3) were associated with an OR of 1.37 (95% CI 1.10–1.76) compared with levels below the 25th percentile (5.9 µg/m3), with a trend of increasing risk of MS with increasing levels of NOx (P <0.0001). A synergistic effect was observed between high NOx levels (exceeding the lower quartile among controls) and the HLA-DRB1*15:01 allele regarding MS risk (AP 0.26, 95% CI 0.13–0.29).Conclusions: Our findings indicate that moderate levels of combustion-related ambient air pollution may play a role in MS development.
|
|
| 10. |
- Hedström, Anna Karin, et al.
(författare)
-
The influence of human leukocyte antigen-DRB1*15:01 and its interaction with smoking in MS development is dependent on DQA1*01:01 status
- 2020
-
Ingår i: Multiple Sclerosis Journal. - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 26:13, s. 1638-1646
-
Tidskriftsartikel (refereegranskat)abstract
- Background: HLA-DRB1*15:01, absence of HLA-A*02:01, and smoking interact to increase multiple sclerosis (MS) risk.Objective: To analyze whether MS-associated human leukocyte antigen (HLA) alleles, apart from DRB1*15:01 and absence of A*02:01, interact with smoking in MS development, and to explore whether the established HLA-smoking interaction is affected by the DQA1*01:01 allele, which confers a protective effect only in the presence of DRB1*15:01.Methods: In two Swedish population-based case-control studies (5838 cases, 5412 controls), subjects with different genotypes and smoking habits were compared regarding MS risk, by calculating odds ratios with 95% confidence intervals employing logistic regression. Interaction on the additive scale between different genotypes and smoking was evaluated.Results: The DRB1*08:01 allele interacted with smoking to increase MS risk. The interaction between DRB1*15:01 and both the absence of A*02:01 and smoking was confined to DQA1*01:01 negative subjects, whereas no interactions occurred among DQA1*01:01 positive subjects.Conclusion: Multifaceted interactions take place between different class II alleles and smoking in MS development. The influence of DRB1*15:01 and its interaction with the absence of A*02:01 and smoking is dependent on DQA1*01:01 status which may be due to differences in the responding T-cell repertoires.
|
|
