| 1. |
- Kleman, Johan, et al.
(författare)
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Rubbat förtroende för forskarna
- 2010
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Ingår i: Svenska Dagbladet. - 1101-2412. ; :25 maj
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 2. |
- Ambikan, Anoop T., et al.
(författare)
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Multi-omics personalized network analyses highlight progressive disruption of central metabolism associated with COVID-19 severity
- 2022
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Ingår i: Cell systems. - : Elsevier BV. - 2405-4712 .- 2405-4720. ; 13:8, s. 665-681
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Tidskriftsartikel (refereegranskat)abstract
- The clinical outcome and disease severity in coronavirus disease 2019 (COVID-19) are heterogeneous, and the progression or fatality of the disease cannot be explained by a single factor like age or comorbidities. In this study, we used system-wide network-based system biology analysis using whole blood RNA sequencing, immunophenotyping by flow cytometry, plasma metabolomics, and single-cell-type metabolo-mics of monocytes to identify the potential determinants of COVID-19 severity at personalized and group levels. Digital cell quantification and immunophenotyping of the mononuclear phagocytes indicated a sub-stantial role in coordinating the immune cells that mediate COVID-19 severity. Stratum-specific and person-alized genome-scale metabolic modeling indicated monocarboxylate transporter family genes (e.g., SLC16A6), nucleoside transporter genes (e.g., SLC29A1), and metabolites such as a-ketoglutarate, succi-nate, malate, and butyrate could play a crucial role in COVID-19 severity. Metabolic perturbations targeting the central metabolic pathway (TCA cycle) can be an alternate treatment strategy in severe COVID-19.
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| 3. |
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| 4. |
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| 5. |
- Bonagas, Nadilly, et al.
(författare)
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Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
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Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
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Tidskriftsartikel (refereegranskat)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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| 6. |
- Boy, M., et al.
(författare)
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Interactions between the atmosphere, cryosphere, and ecosystems at northern high latitudes
- 2019
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 19:3, s. 2015-2061
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Tidskriftsartikel (refereegranskat)abstract
- The Nordic Centre of Excellence CRAICC (Cryosphere-Atmosphere Interactions in a Changing Arctic Climate), funded by NordForsk in the years 2011-2016, is the largest joint Nordic research and innovation initiative to date, aiming to strengthen research and innovation regarding climate change issues in the Nordic region. CRAICC gathered more than 100 scientists from all Nordic countries in a virtual centre with the objectives of identifying and quantifying the major processes controlling Arctic warming and related feedback mechanisms, outlining strategies to mitigate Arctic warming, and developing Nordic Earth system modelling with a focus on short-lived climate forcers (SLCFs), including natural and anthropogenic aerosols. The outcome of CRAICC is reflected in more than 150 peer-reviewed scientific publications, most of which are in the CRAICC special issue of the journal Atmospheric Chemistry and Physics. This paper presents an overview of the main scientific topics investigated in the centre and provides the reader with a state-of-the-art comprehensive summary of what has been achieved in CRAICC with links to the particular publications for further detail. Faced with a vast amount of scientific discovery, we do not claim to completely summarize the results from CRAICC within this paper, but rather concentrate here on the main results which are related to feedback loops in climate change-cryosphere interactions that affect Arctic amplification.
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| 7. |
- Brolin Låftman, Sara, et al.
(författare)
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Problematic alcohol use in the family and adolescents’ stress-related complaints
- 2021
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Ingår i: European Journal of Public Health. - : Oxford University Press (OUP).
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background. A non-negligible proportion of children grow up in families where problematic alcohol use is present. From a resilience perspective and for the implementation of effective interventions, it is relevant to examine to what extent favourable conditions in other contexts may buffer against such family adversities. The aim of the current study was to examine the relationship between problematic familial alcohol use and offspring stress-related complaints. Another aim was to explore whether teacher ratings of the school's degree of student focus can buffer against negative health consequences of problem drinking at home.Methods. Data were drawn from four cross-sectional surveys conducted in 2014 and in 2016 among 8,728 students (∼15-16 years) and 2,024 teachers in 147 Stockholm senior-level school units, with linked school-level register information. Stress-related complaints were measured from students' reports on the weekly co-occurrence of stomach-ache and headache. Teachers' ratings of the school's student focus were measured by an index based on four items which was aggregated to the school level. Student-level sociodemographic characteristics were included as control variables along with the schools' composition and student-teacher ratio. Two-level binary logistic regression analyses were performed.Results. Problematic familial alcohol use was associated with an increased likelihood of stress-related complaints among students (OR 1.74, 95% CI 1.44-2.10). The cross-level interaction revealed that this association was weaker among students in schools with higher levels of student focus.Conclusions. The study showed that the association between problematic familial alcohol use and students' stress-related complaints was less pronounced in schools with higher teacher ratings of student focus. This finding indicates that favourable conditions in schools can buffer against problematic conditions in the family, thus serving a compensatory role.Key messages. Students reporting problematic familial alcohol use were more likely to suffer from stress-related complaints.High teacher ratings of the school’s student focus buffered against the association between problematic familial alcohol use and stress-related complaints.
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| 8. |
- Brolin Låftman, Sara, et al.
(författare)
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School ethos and adolescent gambling : a multilevel study of upper secondary schools in Stockholm, Sweden
- 2020
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gambling is not uncommon among adolescents, and a non-trivial minority has serious problems with gambling. Therefore, enhanced knowledge about factors that may prevent against problematic gambling among youth is needed. Prior research has shown that a strong school ethos, which can be defined as a set of attitudes and values pervading at a school, is associated with a lower inclination among students to engage in various risk behaviours. Knowledge about the link between school ethos and adolescent gambling is however scarce. The aim of the study was to investigate the association between teacher-rated school ethos and student-reported gambling and risk gambling, when controlling also for sociodemographic characteristics at the student- and the school-level.Methods: Data from two separate cross-sectional surveys were combined. The Stockholm School Survey (SSS) was performed among 5123 students (aged 17–18years) in 46 upper secondary schools, and the Stockholm Teacher Survey (STS) was carried out among 1061 teachers in the same schools. School ethos was measured by an index based on teachers’ ratings of 12 items in the STS. Adolescent gambling and risk gambling were based on a set of single items in the SSS. Sociodemographic characteristics at the student-level were measured by student-reported information from the SSS. Information on sociodemographic characteristics at the school-level was retrieved from administrative registers. The statistical method was multilevel regression analysis. Two-level binary logistic regression models were performed.Results: The analyses showed that higher teacher ratings of the school’s ethos were associated with a lower likelihood of gambling and risk gambling among students, when adjusting also for student- and school-level sociodemographic characteristics.Conclusions: This study showed that school ethos was inversely associated with students’ inclination to engage in gambling and in risk gambling. In more general terms, the study provides evidence that schools’ values and norms as reflected by the teachers’ ratings of their school’s ethos have the potential to counteract unwanted behaviours among the students.
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| 9. |
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| 10. |
- Enefalk, Hanna, 1976-, et al.
(författare)
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Totalkonsumtionsmodellen - en kort beskrivning
- 2012
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Ingår i: Samhället, alkoholen och drogerna. - Stockholm : Stockholms universitets förlag. - 9789176566817 ; , s. 63-70
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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