| 1. |
- Green, L, et al.
(författare)
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Data supporting: Invader at the edge - genomic origins and physiological differences of round gobies across a steep urban salinity gradient
- 2022
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Annan publikationabstract
- Species invasions are a global problem of increasing concern, especially in highly connected aquatic environments. Despite this, salinity conditions can pose physiological barriers to their spread and understanding them is important for management. In Scandinavia’s largest cargo port, the invasive round goby (Neogobius melanostomus), is established across a steep salinity gradient. We used 12 937 SNPs to identify the genetic origin and diversity of three sites along the salinity gradient and round goby from western, central and northern Baltic Sea, as well as north European rivers. Fish from two sites from the extreme ends of the gradient were also acclimated to freshwater and seawater, and tested for respiratory and osmoregulatory physiology. Fish from the high salinity environment in the outer port showed higher genetic diversity, and closer relatedness to the other regions, compared to fish from lower salinity upstream the river. Fish from the high salinity site also had higher maximum metabolic rate, fewer blood cells and lower blood Ca2+. Despite these genotypic and phenotypic differences, salinity acclimation affected fish from both sites in the same way: seawater increased the blood osmolality and Na+ levels, and freshwater increased the levels of the stress hormone cortisol. Our results show genotypic and phenotypic differences over short spatial scales across this steep salinity gradient. These patterns of the physiologically robust round goby are likely driven by multiple introductions into the high salinity site, and a process of sorting, likely based on behaviour or selection, along the gradient. Since this euryhaline fish risks spreading from this area, seascape genomics and phenotypic characterisation can inform management strategies even within an area as small as a coastal harbour inlet.
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| 2. |
- Plymale, Andrew E., et al.
(författare)
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Niche Partitioning of Microbial Communities at an Ancient Vitrified Hillfort : Implications for Vitrified Radioactive Waste Disposal
- 2021
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Ingår i: Geomicrobiology Journal. - : Taylor & Francis. - 0149-0451 .- 1521-0529. ; 38:1, s. 36-56
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Tidskriftsartikel (refereegranskat)abstract
- Because microbes cannot be eliminated from radioactive waste disposal facilities, the consequences of bio-colonization must be understood. At a pre-Viking era vitrified hillfort, Broborg, Sweden, anthropogenic glass has been subjected to bio-colonization for over 1,500 years. Broborg is used as a habitat analogue for disposed radioactive waste glass to inform how microbial processes might influence long-term glass durability. Electron microscopy and DNA sequencing of surficial material from the Broborg vitrified wall, adjacent soil, and general topsoil show that the ancient glass supports a niche microbial community of bacteria, fungi, and protists potentially involved in glass alteration. Communities associated with the vitrified wall are distinct and less diverse than soil communities. The vitrified niche of the wall and adjacent soil are dominated by lichens, lichen-associated microbes, and other epilithic, endolithic, and epigeic organisms. These organisms exhibit potential bio-corrosive properties, including silicate dissolution, extraction of essential elements, and secretion of geochemically reactive organic acids, that could be detrimental to glass durability. However, long-term biofilms can also possess a homeostatic function that could limit glass alteration. This study documents potential impacts that microbial colonization and niche partitioning can have on glass alteration, and subsequent release of radionuclides from a disposal facility for vitrified radioactive waste.
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| 3. |
- Rödström, E. Ygland, et al.
(författare)
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Genomic analyses of a large Swedish multi-incident kindred with autosomal dominant Parkinson’s disease with dementia
- 2023
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Ingår i: Parkinsonism & Related Disorders. - 1353-8020. ; 113:Supp, s. 28-29
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Konferensbidrag (refereegranskat)abstract
- Background:The known genetic causes for Parkinson’s disease (PD) onlyexplain a small proportion of the familial aggregation of PD. Despiteintensive efforts by researchers internationally, identifying and confirmingadditional monogenic causes for PD has been difficult.Methods:We examined 16 members of a large family with multi-incidentPD and dementia. Eight members were examined by whole exome (WES)or whole genome sequencing. Rare variants co-segregating with the disease were evaluated based on their distribution in additional familymembers and known gene functions. WES data from 843 PD cases and 885controls were screened for the two most highly ranked candidate variantsand used for gene burden analysis.Results:Clinically, all affected family members had typical PD withcognitive decline. Two affected individuals showed typical PD neuropathology. Out of nine genetic variants identified, we highlighted two as goodcandidates for causing this family’s PD. However, co-segregation with PDwas imperfect and this study was complicated by the fact that somegenotyped family members showed mild motor symptoms of uncertaincause, or cognitive decline without apparent motor dysfunction. Geneburden analysis showed no difference between cases and controls in thefrequency of potentially deleterious variants in the top-candidate genes.Nonetheless, factors that could indicate an impact of either of the two topcandidate genetic variants were found as one of the variants was identifiedin one additional familial PD proband from the case series and geneticvariants in the other top-candidate gene had previously been associatedwith an increased risk for PD in humans.Conclusions: Our study was not able to determine a single high-impactvariant as the cause of PD with cognitive decline in the family despitedetailed clinical and genetic assessments, but we nominate two potentialcandidate variants. Reduced penetrance and phenocopies may complicategenomic studies of families with PD.
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| 4. |
- Abella, J., et al.
(författare)
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SAFEXPLAIN : Safe and Explainable Critical Embedded Systems Based on AI
- 2023
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Ingår i: Proceedings -Design, Automation and Test in Europe, DATE. - : Institute of Electrical and Electronics Engineers Inc.. - 9783981926378
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Konferensbidrag (refereegranskat)abstract
- Deep Learning (DL) techniques are at the heart of most future advanced software functions in Critical Autonomous AI-based Systems (CAIS), where they also represent a major competitive factor. Hence, the economic success of CAIS industries (e.g., automotive, space, railway) depends on their ability to design, implement, qualify, and certify DL-based software products under bounded effort/cost. However, there is a fundamental gap between Functional Safety (FUSA) requirements on CAIS and the nature of DL solutions. This gap stems from the development process of DL libraries and affects high-level safety concepts such as (1) explainability and traceability, (2) suitability for varying safety requirements, (3) FUSA-compliant implementations, and (4) real-time constraints. As a matter of fact, the data-dependent and stochastic nature of DL algorithms clashes with current FUSA practice, which instead builds on deterministic, verifiable, and pass/fail test-based software. The SAFEXPLAIN project tackles these challenges and targets by providing a flexible approach to allow the certification - hence adoption - of DL-based solutions in CAIS building on: (1) DL solutions that provide end-to-end traceability, with specific approaches to explain whether predictions can be trusted and strategies to reach (and prove) correct operation, in accordance to certification standards; (2) alternative and increasingly sophisticated design safety patterns for DL with varying criticality and fault tolerance requirements; (3) DL library implementations that adhere to safety requirements; and (4) computing platform configurations, to regain determinism, and probabilistic timing analyses, to handle the remaining non-determinism.
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| 5. |
- Capo, Eric, et al.
(författare)
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Lake sedimentary dna research on past terrestrial and aquatic biodiversity: Overview and recommendations
- 2021
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Ingår i: Quaternary. - : MDPI. - 2571-550X. ; 4:1
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Forskningsöversikt (refereegranskat)abstract
- The use of lake sedimentary DNA to track the long-term changes in both terrestrial and aquatic biota is a rapidly advancing field in paleoecological research. Although largely applied nowadays, knowledge gaps remain in this field and there is therefore still research to be conducted to ensure the reliability of the sedimentary DNA signal. Building on the most recent literature and seven original case studies, we synthesize the state-of-the-art analytical procedures for effective sampling, extraction, amplification, quantification and/or generation of DNA inventories from sedimentary ancient DNA (sedaDNA) via high-throughput sequencing technologies. We provide recommendations based on current knowledge and best practises.
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| 6. |
- Diarbakerli, E., et al.
(författare)
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Learning from the past to plan for the future: A scoping review of musculoskeletal clinical research in Sweden 2010-2020
- 2022
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 127:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aims of this study are to 1) determine the scope of musculoskeletal (MSK)-related clinical research in Sweden; 2) collate the amount of first-tier funding received; 3) discuss strategies and infrastructure supporting future MSK clinical trials in Sweden. Methods: A systematic scoping review protocol was applied in PubMed, Scopus, and SweCRIS databases. The articles were examined, and data were extracted in multiple stages by three blinded authors. Results: The search strategy resulted in 3,025 publications from 479 Swedish-affiliated authors. Primary health care was the basis for 14% of the publications, 84% from secondary health care, and 2% from occupational health care with a similar proportional distribution of first-tier research grant financing. Approximately one in six publications were randomized controlled trials (RCTs), while the majority were of observational cohort design. The majority of publications in primary and occupational health care were related to pain disorders (51 and 67%, respectively), especially diagnosis, prognosis, and healthcare organizational-related interventions (34%) and rehabilitation (15%) with similar proportional distribution of first-tier research grant financing. In secondary health care, rheumatic inflammatory disorder-related publications were most prevalent (30%), most frequently concerning diagnosis, prognosis, and healthcare organizational-related interventions (20%), attracting approximately half of all first-tier funding. Publications related to degenerative joint disorders (25%), fractures (16%), and joint, tendon, and muscle injuries (13%) frequently concerned surgical and other orthopedic-related interventions (16, 6, and 8%, respectively). Pain disorder-related publications (10%) as well as bone health and osteoporosis-related publications (4%) most frequently concerned diagnosis, prognosis, and healthcare organizational-related interventions (5 and 3%, respectively). Conclusions: Swedish-affiliated MSK disorder research 2010-2020 was predominantly observational cohort rather than RCT based. There was skewed first-tier funding allocation considering prevalence/incidence and burden of disease. Use of infrastructure supporting register-based RCTs, placebo-controlled RCTs, and hybrid effectiveness-implementation studies on prevention and clinical intervention is important strategies for the future in all healthcare sectors.
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| 7. |
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| 8. |
- Garza, Raquel, et al.
(författare)
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LINE-1 retrotransposons drive human neuronal transcriptome complexity and functional diversification
- 2023
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Ingår i: Science Advances. - 2375-2548. ; 9:44
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Tidskriftsartikel (refereegranskat)abstract
- The genetic mechanisms underlying the expansion in size and complexity of the human brain remain poorly understood. Long interspersed nuclear element-1 (L1) retrotransposons are a source of divergent genetic information in hominoid genomes, but their importance in physiological functions and their contribution to human brain evolution are largely unknown. Using multiomics profiling, we here demonstrate that L1 promoters are dynamically active in the developing and the adult human brain. L1s generate hundreds of developmentally regulated and cell type-specific transcripts, many that are co-opted as chimeric transcripts or regulatory RNAs. One L1-derived long noncoding RNA, LINC01876, is a human-specific transcript expressed exclusively during brain development. CRISPR interference silencing of LINC01876 results in reduced size of cerebral organoids and premature differentiation of neural progenitors, implicating L1s in human-specific developmental processes. In summary, our results demonstrate that L1-derived transcripts provide a previously undescribed layer of primate- and human-specific transcriptome complexity that contributes to the functional diversification of the human brain.
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| 9. |
- Granholm, Ann-Charlotte E, et al.
(författare)
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Neuropathological findings in Down syndrome, Alzheimer's disease and control patients with and without SARS-COV-2 : preliminary findings
- 2024
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Ingår i: Acta Neuropathologica. - 1432-0533. ; 147, s. 1-21
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Tidskriftsartikel (refereegranskat)abstract
- The SARS-CoV-2 virus that led to COVID-19 is associated with significant and long-lasting neurologic symptoms in many patients, with an increased mortality risk for people with Alzheimer's disease (AD) and/or Down syndrome (DS). However, few studies have evaluated the neuropathological and inflammatory sequelae in postmortem brain tissue obtained from AD and people with DS with severe SARS-CoV-2 infections. We examined tau, beta-amyloid (Aβ), inflammatory markers and SARS-CoV-2 nucleoprotein in DS, AD, and healthy non-demented controls with COVID-19 and compared with non-infected brain tissue from each disease group (total n = 24). A nested ANOVA was used to determine regional effects of the COVID-19 infection on arborization of astrocytes (Sholl analysis) and percent-stained area of Iba-1 and TMEM 119. SARS-CoV-2 antibodies labeled neurons and glial cells in the frontal cortex of all subjects with COVID-19, and in the hippocampus of two of the three DS COVID-19 cases. SARS-CoV-2-related alterations were observed in peri-vascular astrocytes and microglial cells in the gray matter of the frontal cortex, hippocampus, and para-hippocampal gyrus. Bright field microscopy revealed scattered intracellular and diffuse extracellular Aβ deposits in the hippocampus of controls with confirmed SARS-CoV-2 infections. Overall, the present preliminary findings suggest that SARS-CoV-2 infections induce abnormal inflammatory responses in Down syndrome.
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| 10. |
- Ilinca, A., et al.
(författare)
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MAP3K6 Mutations in a Neurovascular Disease Causing Stroke, Cognitive Impairment, and Tremor
- 2021
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Ingår i: Neurology-Genetics. - : Ovid Technologies (Wolters Kluwer Health). - 2376-7839. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective To describe a possible novel genetic mechanism for cerebral small vessel disease (cSVD) and stroke. Methods We studied a Swedish kindred with ischemic stroke and intracerebral hemorrhage, tremor, dysautonomia, and mild cognitive decline. Members were examined clinically, radiologically, and by histopathology. Genetic workup included whole-exome sequencing (WES) and whole-genome sequencing (WGS) and intrafamilial cosegregation analyses. Results Fifteen family members were examined clinically. Twelve affected individuals had white matter hyperintensities and 1 or more of (1) stroke episodes, (2) clinically silent lacunar ischemic lesions, and (3) cognitive dysfunction. All affected individuals had tremor and/or atactic gait disturbance. Mild symmetric basal ganglia calcifications were seen in 3 affected members. Postmortem examination of 1 affected member showed pathologic alterations in both small and large arteries the brain. Skin biopsies of 3 affected members showed extracellular amorphous deposits within the subepidermal zone, which may represent degenerated arterioles. WES or WGS did not reveal any potentially disease-causing variants in known genes for cSVDs or idiopathic basal ganglia calcification, but identified 1 heterozygous variant, NM_004672.4 MAP3K6 c.322G>A p.(Asp108Asn), that cosegregated with the disease in this large family. MAP3K6 has known functions in angiogenesis and affects vascular endothelial growth factor expression, which may be implicated in cerebrovascular disease. Conclusions Our data strongly suggest the MAP3K6 variant to be causative for this novel disease phenotype, but the absence of functional data and the present lack of additional families with this disease and MAP3K6 mutations still limit the formal evidence for the variant's pathogenicity.
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