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- Feng, Shaohong, et al.
(författare)
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Dense sampling of bird diversity increases power of comparative genomics
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587:7833
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Tidskriftsartikel (refereegranskat)abstract
- Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity(1-4). Sparse taxon sampling has previously been proposed to confound phylogenetic inference(5), and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species. A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.
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- Liu, Z. G., et al.
(författare)
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Hemizygous variants in protein phosphatase 1 regulatory subunit 3F (PPP1R3F) are associated with a neurodevelopmental disorder characterized by developmental delay, intellectual disability and autistic features
- 2023
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Ingår i: Human Molecular Genetics. - 0964-6906 .- 1460-2083. ; 32:20, s. 2981-2995
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Tidskriftsartikel (refereegranskat)abstract
- Protein phosphatase 1 regulatory subunit 3F (PPP1R3F) is a member of the glycogen targeting subunits (GTSs), which belong to the large group of regulatory subunits of protein phosphatase 1 (PP1), a major eukaryotic serine/threonine protein phosphatase that regulates diverse cellular processes. Here, we describe the identification of hemizygous variants in PPP1R3F associated with a novel X-linked recessive neurodevelopmental disorder in 13 unrelated individuals. This disorder is characterized by developmental delay, mild intellectual disability, neurobehavioral issues such as autism spectrum disorder, seizures and other neurological findings including tone, gait and cerebellar abnormalities. PPP1R3F variants segregated with disease in affected hemizygous males that inherited the variants from their heterozygous carrier mothers. We show that PPP1R3F is predominantly expressed in brain astrocytes and localizes to the endoplasmic reticulum in cells. Glycogen content in PPP1R3F knockout astrocytoma cells appears to be more sensitive to fluxes in extracellular glucose levels than in wild-type cells, suggesting that PPP1R3F functions in maintaining steady brain glycogen levels under changing glucose conditions. We performed functional studies on nine of the identified variants and observed defects in PP1 binding, protein stability, subcellular localization and regulation of glycogen metabolism in most of them. Collectively, the genetic and molecular data indicate that deleterious variants in PPP1R3F are associated with a new X-linked disorder of glycogen metabolism, highlighting the critical role of GTSs in neurological development. This research expands our understanding of neurodevelopmental disorders and the role of PP1 in brain development and proper function.
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- Tommasini, R., et al.
(författare)
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Accepted Tutorials at The Web Conference 2022
- 2022
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Ingår i: WWW 2022 - Companion Proceedings of the Web Conference 2022. - New York, NY, USA : Association for Computing Machinery (ACM). ; , s. 391-399
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Konferensbidrag (refereegranskat)abstract
- This paper summarizes the content of the 20 tutorials that have been given at The Web Conference 2022: 85% of these tutorials are lecture style, and 15% of these are hands on.
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| 8. |
- Andrighetto, Giulia, et al.
(författare)
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Changes in social norms during the early stages of the COVID-19 pandemic across 43 countries
- 2024
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Ingår i: Nature Communications. - : NATURE PORTFOLIO. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- The emergence of COVID-19 dramatically changed social behavior across societies and contexts. Here we study whether social norms also changed. Specifically, we study this question for cultural tightness (the degree to which societies generally have strong norms), specific social norms (e.g. stealing, hand washing), and norms about enforcement, using survey data from 30,431 respondents in 43 countries recorded before and in the early stages following the emergence of COVID-19. Using variation in disease intensity, we shed light on the mechanisms predicting changes in social norm measures. We find evidence that, after the emergence of the COVID-19 pandemic, hand washing norms increased while tightness and punishing frequency slightly decreased but observe no evidence for a robust change in most other norms. Thus, at least in the short term, our findings suggest that cultures are largely stable to pandemic threats except in those norms, hand washing in this case, that are perceived to be directly relevant to dealing with the collective threat. Tightness-looseness theory predicts that social norms strengthen following threat. Here the authors test this and find that, after the emergence of the COVID-19 pandemic, hand washing norms increased, but no evidence was observed for a robust change in most other norms.
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- Bocskei, RM, et al.
(författare)
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Oscillometrically Measured Aortic Pulse Wave Velocity Reveals Asymptomatic Carotid Atherosclerosis in a Middle-Aged, Apparently Healthy Population
- 2020
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Ingår i: BioMed research international. - : Hindawi Limited. - 2314-6141 .- 2314-6133. ; 2020, s. 8571062-
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Tidskriftsartikel (refereegranskat)abstract
- Background. Asymptomatic atherosclerosis is a common entity even at young age. Studies have suggested a strong relationship between increased arterial stiffness and asymptomatic carotid atherosclerosis (ACA) in general population, particularly in those with high cardiovascular risk, but no data exist from a younger population free from recognized cardiovascular disease. Hypothesis. We hypothesized there is an association between ACA and aortic pulse wave velocity (PWVao) in middle-aged, apparently healthy, normotensive population to reveal increased cardiovascular risk. Methods. We examined the relationship between ACA and PWVao in 236 apparently healthy, asymptomatic, normotensive, middle-aged subjects (age 47 ± 8 years; 52% women). PWVao was measured with the oscillometric method (Arteriograph). ACA was assessed by carotid artery ultrasonography. Results. ACA was present in 51 subjects. Subjects with ACA were older (p<0.009), more likely to be smokers (p<0.001), and had higher systolic blood pressure (SBP, 128 ± 9 vs. 125 ± 10 mmHg, p=0.048) and PWVao (9.3 ± 1.6 vs. 7.9 ± 1.3 m/s, p<0.001) than subjects without ACA. In a stepwise logistic regression analysis, only PWVao (odds ratio: 1.88, p<0.001), smoking habit (odds ratio 3.79, p=0.003), systolic blood pressure (odds ratio 1.05, p=0.046), and diastolic blood pressure (odds ratio: 0.94, p=0.038) were independently associated with ACA. PWVao >8.3 m/s identified ACA with a 71% sensitivity, 65% specificity, 36% positive and 89% negative predictive value, 2.04 relative risk, and 4.54 odds ratio, respectively. Conclusions. PWVao measured by the Arteriograph proved to be an independent marker of ACA. Our study may reveal high CV risk, detected as increased PWVao, which according to our study is related in a very high probability to asymptomatic carotid atherosclerosis in apparently healthy, young, and middle-aged subjects.
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- Jing, X, et al.
(författare)
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COVID-19 instigates adipose browning and atrophy through VEGF in small mammals
- 2022
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Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 4:12, s. 1674-
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Tidskriftsartikel (refereegranskat)abstract
- Patients with COVID-19 frequently manifest adipose atrophy, weight loss and cachexia, which significantly contribute to poor quality of life and mortality1,2. Browning of white adipose tissue and activation of brown adipose tissue are effective processes for energy expenditure3–7; however, mechanistic and functional links between SARS-CoV-2 infection and adipose thermogenesis have not been studied. In this study, we provide experimental evidence that SARS-CoV-2 infection augments adipose browning and non-shivering thermogenesis (NST), which contributes to adipose atrophy and body weight loss. In mouse and hamster models, SARS-CoV-2 infection activates brown adipose tissue and instigates a browning or beige phenotype of white adipose tissues, including augmented NST. This browning phenotype was also observed in post-mortem adipose tissue of four patients who died of COVID-19. Mechanistically, high levels of vascular endothelial growth factor (VEGF) in the adipose tissue induces adipose browning through vasculature–adipocyte interaction. Inhibition of VEGF blocks COVID-19-induced adipose tissue browning and NST and partially prevents infection-induced body weight loss. Our data suggest that the browning of adipose tissues induced by COVID-19 can contribute to adipose tissue atrophy and weight loss observed during infection. Inhibition of VEGF signaling may represent an effective approach for preventing and treating COVID-19-associated weight loss.
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| 12. |
- Lagerqvist, Nina, et al.
(författare)
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Evaluation of 11 SARS-CoV-2 antibody tests by using samples from patients with defined IgG antibody titers
- 2021
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the performance of 11 SARS-CoV-2 antibody tests using a reference set of heat-inactivated samples from 278 unexposed persons and 258 COVID-19 patients, some of whom contributed serial samples. The reference set included samples with a variation in SARS-CoV-2 IgG antibody titers, as determined by an in-house immunofluorescence assay (IFA). The five evaluated rapid diagnostic tests had a specificity of 99.0% and a sensitivity that ranged from 56.3 to 81.6% and decreased with low IFA IgG titers. The specificity was > 99% for five out of six platform-based tests, and when assessed using samples collected ≥ 22 days after symptom onset, two assays had a sensitivity of > 96%. These two assays also detected samples with low IFA titers more frequently than the other assays. In conclusion, the evaluated antibody tests showed a heterogeneity in their performances and only a few tests performed well with samples having low IFA IgG titers, an important aspect for diagnostics and epidemiological investigations.
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| 13. |
- Pablos, Isabel, et al.
(författare)
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Mechanistic insights into COVID-19 by global analysis of the SARS-CoV-2 3CL(pro) substrate degradome
- 2021
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Ingår i: Cell Reports. - : Cell Press. - 2211-1247. ; 37:4
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Tidskriftsartikel (refereegranskat)abstract
- The main viral protease (3CL(pro)) is indispensable for SARS-CoV-2 replication. We delineate the human protein substrate landscape of 3CL(pro) by TAILS substrate-targeted N-terminomics. We identify more than 100 substrates in human lung and kidney cells supported by analyses of SARS-CoV-2-infected cells. Enzyme kinetics and molecular docking simulations of 3CL(pro) engaging substrates reveal how noncanonical cleavage sites, which diverge from SARS-CoV, guide substrate specificity. Cleaving the interactors of essential effector proteins, effectively stranding them from their binding partners, amplifies the consequences of proteolysis. We show that 3CL(pro) targets the Hippo pathway, including inactivation of MAP4K5, and key effectors of transcription, mRNA processing, and translation. We demonstrate that Spike glycoprotein directly binds galectin-8, with galectin-8 cleavage disengaging CALCOCO2/NDP52 to decouple antiviral-autophagy. Indeed, in post-mortem COVID-19 lung samples, NDP52 rarely colocalizes with galectin-8, unlike in healthy lungs. The 3CL(pro) substrate degradome establishes a foundational substrate atlas to accelerate exploration of SARSCoV-2 pathology and drug design.
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| 14. |
- Scharnweber, Kristin, 1983-, et al.
(författare)
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Comprehensive analysis of chemical and biological problems associated with browning agents used in aquatic studies
- 2021
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Ingår i: Limnology and Oceanography. - : Wiley. - 1541-5856. ; 19:12, s. 818-835
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Tidskriftsartikel (refereegranskat)abstract
- Inland waters receive and process large amounts of colored organic matter from the terrestrial surroundings. These inputs dramatically affect the chemical, physical, and biological properties of water bodies, as well as their roles as global carbon sinks and sources. However, manipulative studies, especially at ecosystem scale, require large amounts of dissolved organic matter with optical and chemical properties resembling indigenous organic matter. Here, we compared the impacts of two leonardite products (HuminFeed and SuperHume) and a freshly derived reverse osmosis concentrate of organic matter in a set of comprehensive mesocosm- and laboratory-scale experiments and analyses. The chemical properties of the reverse osmosis concentrate and the leonardite products were very different, with leonardite products being low and the reverse osmosis concentrate being high in carboxylic functional groups. Light had a strong impact on the properties of leonardite products, including loss of color and increased particle formation. HuminFeed presented a substantial impact on microbial communities under light conditions, where bacterial production was stimulated and community composition modified, while in dark potential inhibition of bacterial processes was detected. While none of the browning agents inhibited the growth of the tested phytoplankton Gonyostomum semen, HuminFeed had detrimental effects on zooplankton abundance and Daphnia reproduction. We conclude that the effects of browning agents extracted from leonardite, particularly HuminFeed, are in sharp contrast to those originating from terrestrially derived dissolved organic matter. Hence, they should be used with great caution in experimental studies on the consequences of terrestrial carbon for aquatic systems.
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| 15. |
- Walther, G, et al.
(författare)
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Report on challenges for SCIs
- 2021
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This report discusses the challenges posed by four types of threats – terrorist attacks, cyber-attacks, extreme weather and social unrest – on the following eight smart critical infrastructure systems:a.ALPHA - Finance (financial system): The analysis focuses on disturbed information flow and disabling/manipulating IT and communication systems, including attacks on the “physical layer” using the example of IEMI/HPEM threats, as well as the software layer.b. BRAVO - Energy supply (system): The analysis focuses on disruption of “smart” energy supply in a “smart city”, caused by natural hazards, in this case flooding, leading to cascading effects and severe consequences for other energy-depending SCIs.c. CHARLIE - Health care (system):Focus of the analysis is on all threats that might cause large increases in the numbers of injuries or sick patients within a densely populated area. This will include indirect impacts, e.g. large numbers of injuries caused by a disaster or terrorist attacks or disease epidemics, but also direct impacts, e.g. service disruptions in critical health infrastructures, such as hospitals, due to attacks or disasters hitting the infrastructure itself.d.DELTA - Transportation (system) – airports: According to the framework situation, threats on Smart Airports will be assessed under circumstances of (i) blocked traffic, (ii) passenger and airplane traffic exceeding capacity (iii) flood.e. ECHO - Industry (in zones in cities) "Industrial Production Plants":The analysis focuses mainly on technological accidents within the refinery complex, but also accidents caused by natural hazards affecting refinery property outside the main refinery complex, e.g. accident on jetty belonging to refinery on the river Danube during unloading/loading oil products from barge to a tank, damages by a gale or storm on process installations (pipes, hoses) resulting in river pollution. Both scenarios could lead to cascading effects for other SCIs in close vicinity.f. FOXTROT - Water supply (systems): The analysis focuses on three cases of local and regional drinking water supply chains, with different kinds of vulnerabilities in terms of climate threats, ICT challenges, security issues and human error.g.GOLF - Urban flood protection (systems): The analysis focuses in the disruption of water and transport caused through tidal and fluvial flooding events.h. HOTEL: City of Helsinki - Flooding underground coal storage. Resilience of the energy infrastructure (city environment).The way this analysis was conducted was by assessing these threats using a 5x5 framework matrix. The two axes of the matrix were phases (understand risks, anticipate/prepare, absorb/withstand, respond/recover, adapt/learn) and dimensions (system/physical, information/data, organizational/business, societal/political, cognitive/decision-making).Each individual matrix block was discussed by subject experts who identified specific challenges and implications for each matrix element and rated its relevance (high, medium, low).In terms of the results, the system/physical dimension received the highest number of important challenges.Overall, the most important singular element was to understand risks in the organizational/business dimension. The least importance was attributed to the adapt/learn phase.
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