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1.	Pham, T, et al. (författare) Outcomes of Patients Presenting with Mild Acute Respiratory Distress Syndrome: Insights from the LUNG SAFE Study 2019 Ingår i: Anesthesiology. - : Lippincott Williams and Wilkins. - 1528-1175 .- 0003-3022. ; 130:2, s. 263-283 Tidskriftsartikel (refereegranskat)
2.	Moberg, Christina, et al. (författare) De unga gör helt rätt när de stämmer staten 2022 Ingår i: Aftonbladet. - 1103-9000. Tidskriftsartikel (populärvet., debatt m.m.)abstract 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
3.	Ademuyiwa, Adesoji O., et al. (författare) Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries 2016 Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4 Tidskriftsartikel (refereegranskat)abstract Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
4.	Chavez-Valdez, R., et al. (författare) Evidence for Sexual Dimorphism in the Response to TLR3 Activation in the Developing Neonatal Mouse Brain: A Pilot Study 2019 Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 10 Tidskriftsartikel (refereegranskat)abstract Toll-like receptor (TLR)3 activation during the neonatal period produces responses linked to the origins of neuropsychiatric disorders. Although there is sexual dimorphism in neuropsychiatric disorders, it is unknown if brain responses to TLR3 activation are sex-specific. We hypothesized that poly I:C in a post-natal day (P)8 model induces a sexually dimorphic inflammatory responses. C57BL6 mice received intraperitoneal injection of poly I:C (10 mg/kg) or vehicle [normal saline (NS)] at P8. Pups were killed at 6 or 14 h for caspase 3 and 8 activity assays, NFkB ELISA, IRF3, AP1, and GFAP western blotting and cytokines/chemokines gene expression real time qRT-PCR (4-6/group). A second group of pups were killed at 24 h (P9) or 7 days (P15) after poly I:C to assess astrocytic (GFAP) and microglia (Iba1) activation in the hippocampus, thalamus and cortex using immunohistochemistry, and gene and protein expression of cytokines/chemokines using real time RT-PCR and MSD, respectively (4-6/group). Nonparametric analysis was applied. Six hours after poly I:C, caspase-3 and -8 activities in cytosolic fractions were 1.6 and 2.8-fold higher in poly I:C-treated than in NS-treated female mice, respectively, while gene expressions of pro-inflammatory cytokines were upregulated in both sexes. After poly I:C, IRF3 nuclear translocation occurred earlier (6 h) in female mice and later (14 h) in male mice. At 14 h after poly I:C, only male mice also had increased nuclear NF kappa B levels (88%, p < 0.001) and GFAP expression coinciding with persistent IL-6 and FAS gene upregulation (110 and 77%, respectively; p < 0.001) and IL-10 gene downregulation (-42%, p < 0.05). At 24 h after poly I:C, IL-1 beta, CXCL-10, TNF-alpha, and MCP-1 were similarly increased in both sexes but at 7 days after exposure, CXCL-10 and INF gamma were increased and IL-10 was decreased only in female mice. Accordingly, microglial activation persisted at 7 days after poly I:C in the hippocampus, thalamus and cortex of female mice. This preliminary study suggests that TLR3 activation may produce in the developing neonatal mouse brain a sexually dimorphic response with early activation of caspase-dependent pathways in female mice, activation of inflammatory cascades in both sexes, which then persists in female mice. Further well-powered studies are essential to confirm these sex-specific findings.
5.	Huusko, Linnea L., et al. (författare) Climate sensitivity indices and their relation with projected temperature change in CMIP6 models 2021 Ingår i: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 16:6 Tidskriftsartikel (refereegranskat)abstract Equilibrium climate sensitivity (ECS) and transient climate response (TCR) are both measures of the sensitivity of the climate system to external forcing, in terms of temperature response to CO2 doubling. Here it is shown that, of the two, TCR in current-generation coupled climate models is better correlated with the model projected temperature change from the pre-industrial state, not only on decadal time scales but throughout much of the 21st century. For strong mitigation scenarios the difference persists until the end of the century. Historical forcing on the other hand has a significant degree of predictive power of past temperature evolution in the models, but is not relevant to the magnitude of temperature change in their future projections. Regional analysis shows a superior predictive power of ECS over TCR during the latter half of the 21st century in areas with slow warming, illustrating that although TCR is a better predictor of warming on a global scale, it does not capture delayed regional feedbacks, or pattern effects. The transient warming at CO2 quadrupling (T140) is found to be correlated with global mean temperature anomaly for a longer time than TCR, and it also better describes the pattern of regional temperature anomaly at the end of the century. Over the 20th century, there is a weak correlation between total forcing and ECS, contributing to, but not determining, the model agreement with observed warming. ECS and aerosol forcing in the models are not correlated.
6.	Petersson, C. L.M., et al. (författare) Anisotropic photoemission time delays close to a Fano resonance 2018 Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9 Tidskriftsartikel (refereegranskat)abstract Electron correlation and multielectron effects are fundamental interactions that govern many physical and chemical processes in atomic, molecular and solid state systems. The process of autoionization, induced by resonant excitation of electrons into discrete states present in the spectral continuum of atomic and molecular targets, is mediated by electron correlation. Here we investigate the attosecond photoemission dynamics in argon in the 20-40 eV spectral range, in the vicinity of the 3s(-1)np autoionizing resonances. We present measurements of the differential photoionization cross section and extract energy and angle-dependent atomic time delays with an attosecond interferometric method. With the support of a theoretical model, we are able to attribute a large part of the measured time delay anisotropy to the presence of autoionizing resonances, which not only distort the phase of the emitted photoelectron wave packet but also introduce an angular dependence.
7.	Wenzel, H. H. B., et al. (författare) A federated approach to identify women with early-stage cervical cancer at low risk of lymph node metastases 2023 Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 185, s. 61-68 Tidskriftsartikel (refereegranskat)abstract Objective: Lymph node metastases (pN+) in presumed early-stage cervical cancer negatively impact prognosis. Using federated learning, we aimed to develop a tool to identify a group of women at low risk of pN+, to guide the shared decision-making process concerning the extent of lymph node dissection.Methods: Women with cervical cancer between 2005 and 2020 were identified retrospectively from population-based registries: the Danish Gynaecological Cancer Database, Swedish Quality Registry for Gynaecologic Cancer and Netherlands Cancer Registry. Inclusion cri-teria were: squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma; The International Federation of Gynecology and Obstetrics 2009 IA2, IB1 and IIA1; treatment with radical hysterectomy and pelvic lymph node assessment. We applied privacy-preserving federated logistic regression to identify risk factors of pN+. Significant factors were used to stratify the risk of pN+. Results: We included 3606 women (pN+ 11%). The most important risk factors of pN+ were lymphovascular space invasion (LVSI) (odds ratio [OR] 5.16, 95% confidence interval [CI], 4.59-5.79), tumour size 21-40 mm (OR 2.14, 95% CI, 1.89-2.43) and depth of invasion > 10 mm (OR 1.81, 95% CI, 1.59-2.08). A group of 1469 women (41%)-with tumours without LVSI, tumour size 520 mm, and depth of invasion 510 mm-had a very low risk of pN + (2.4%, 95% CI, 1.7-3.3%). Conclusion: Early-stage cervical cancer without LVSI, a tumour size 520 mm and depth of invasion 510 mm, confers a low risk of pN+. Based on an international privacy-preserving analysis, we developed a useful tool to guide the shared decision-making process regarding lymph node dissection.& COPY; 2023 Elsevier Ltd. All rights reserved.
8.	Abarkan, Abdellah, et al. (författare) Corona hotar förvärra svenska bostadskrisen. 108 forskare: Sveriges regering och kommuner måste förhindra en katastrof. 2020 Ingår i: Aftonbladet. - 1103-9000. Tidskriftsartikel (populärvet., debatt m.m.)abstract Debattartikel och Öppet brev publicerad i tidningen Aftonbladet. 29.3. 2020.
9.	Amberntsson, Anna, et al. (författare) Maternal vitamin D status and risk of childhood overweight at 5 years of age in two Nordic cohort studies 2023 Ingår i: Frontiers in Nutrition. - 2296-861X. ; 10 Tidskriftsartikel (refereegranskat)abstract IntroductionMaternal vitamin D status during pregnancy has been suggested to have a role in childhood adiposity development, but results are conflicting. Our aims were to investigate [1] the relationships between maternal 25-hydroxyvitamin D (25OHD) during pregnancy and the child's body mass index (BMI) and risk of overweight at 5 years of age, and [2] maternal pre-pregnancy BMI as effect modifier for these associations. MethodsData sources included a subsample from the Norwegian Mother, Father and Child Cohort Study (MoBa sub-cohort; N = 2,744) and the Swedish GraviD cohort study (N = 891). Maternal 25OHD was analyzed in gestational week 18 in the MoBa sub-cohort and week 10 in the GraviD cohort. In the MoBa sub-cohort, parents reported their child's documented measures of weight and length or height from the health card at routine check-up. In the GraviD cohort, this information was collected directly from medical records. Childhood overweight (including obesity) was identified using the International Obesity Task Force cut-offs. Linear and logistic regression models were used to investigate the association between maternal 25OHD and child's BMI and risk of overweight at 5 years of age in each cohort separately, and in a pooled dataset. ResultsIn the pooled analysis, maternal 25OHD <30 nmol/L was associated with lower BMI in children at 5 years of age, but not with risk of overweight. Interaction analysis showed that the association was predominant among children of mothers with pre-pregnancy BMI & GE;25 kg/m(2). ConclusionLow maternal vitamin D status, particularly in mothers with overweight or obesity, predicted lower BMI in their five-year-old children. However, there was no evidence of an effect on overweight in these children.
10.	Amberntsson, Anna, et al. (författare) Maternal vitamin D status in relation to infant BMI growth trajectories up to 2 years of age in two prospective pregnancy cohorts 2022 Ingår i: Obesity Science & Practice. - : Wiley. - 2055-2238. ; 8:5, s. 670-681 Tidskriftsartikel (refereegranskat)abstract Background: Early childhood growth can affect the child's health status later in life. Maternal vitamin D status has been suggested to affect early childhood growth. However, there is a lack of studies investigating the role of maternal vitamin D status on growth trajectories during infancy. By using growth mixture modeling (GMM), maternal vitamin D status during pregnancy can be investigated in relation to different classes of infant growth trajectories. Objectives: To examine the association between maternal 25-hydroxyvitamin D (25OHD) and classes of infant body mass index (BMI) growth trajectories. Methods: Mother-child pairs were included from the Norwegian Mother, Father, and Child Cohort Study (MoBa, n = 2522) and the Swedish GraviD cohort (n = 862). Maternal 25OHD in pregnancy was analyzed by liquid chromatography tandem mass spectrometry. Children's weights and heights were registry-based. GMM identified classes of infant BMI growth trajectories up to 2 years. The association between maternal 25OHD and infant BMI class by cohort was estimated using a log-link generalized linear model. Mixed model analysis estimated the pooled association including both cohorts. Results: Two infant BMI classes were identified, stable normal and stable high. In MoBa, maternal 25OHD <50 and 50-75 nmol/L were associated (RR 2.70, 95% CI 1.26-5.77 and RR 2.56, 95% CI 1.20-5.47) with a higher risk of the infant stable high BMI class, compared with 25OHD >75 nmol/L. In GraviD, no association was found. In pooled analysis, maternal 25OHD <= 75 nmol/L was non-significantly associated with a higher risk of the stable high BMI growth class. Conclusions: Maternal 250HD <= 75 nmol/L may be associated with a higher class of BMI growth trajectory during infancy.
11.	Amberntsson, Anna, et al. (författare) Vitamin D intake and determinants of vitamin D status during pregnancy in The Norwegian Mother, Father and Child Cohort Study 2023 Ingår i: Frontiers in Nutrition. - 2296-861X. ; 10 Tidskriftsartikel (refereegranskat)abstract BackgroundNorwegian data on vitamin D status among pregnant women indicate a moderate to high prevalence of insufficient vitamin D status (25-hydroxyvitamin D (25OHD) concentrations & LE;50 nmol/L). There is a lack of population-based research on vitamin D intake and determinants of 25OHD in pregnant women from northern latitudes. The aims of this study were (1) to evaluate total vitamin D intake from both diet and supplements, (2) to investigate determinants of vitamin D status, and (3) to investigate the predicted response in vitamin D status by total vitamin D intake, in pregnant Norwegian women. MethodsIn total, 2,960 pregnant women from The Norwegian Environmental Biobank, a sub-study within The Norwegian Mother, Father and Child Cohort Study (MoBa), were included. Total vitamin D intake was estimated from a food frequency questionnaire in gestational week 22. Concentrations of plasma 25OHD was analyzed by automated chemiluminescent microparticle immunoassay method in gestational week 18. Candidate determinant variables of 25OHD were chosen using stepwise backward selection and investigated using multivariable linear regression. Predicted 25OHD by total vitamin D intake, overall and stratified by season and pre-pregnancy BMI, was explored using restricted cubic splines in an adjusted linear regression. ResultsOverall, about 61% of the women had a total vitamin D intake below the recommended intake. The main contributors to total vitamin D intake were vitamin D supplements, fish, and fortified margarine. Higher 25OHD concentrations were associated with (in descending order of the beta estimates) summer season, use of solarium, higher vitamin D intake from supplements, origin from high income country, lower pre-pregnancy BMI, higher age, higher vitamin D intake from foods, no smoking during pregnancy, higher education and energy intake. During October-May, a vitamin D intake according to the recommended intake was predicted to reach sufficient 25OHD concentrations >50 nmoL/L. ConclusionThe findings from this study highlight the importance of the vitamin D intake, as one of few modifiable determinants, to reach sufficient 25OHD concentrations during months when dermal synthesis of vitamin D is absent.
12.	Bartke, Katrin, et al. (författare) Genetic Architecture and Fitness of Bacterial Interspecies Hybrids 2021 Ingår i: Molecular biology and evolution. - : Oxford University Press. - 0737-4038 .- 1537-1719. ; 38:4, s. 1472-1481 Tidskriftsartikel (refereegranskat)abstract Integration of a conjugative plasmid into a bacterial chromosome can promote the transfer of chromosomal DNA to other bacteria. Intraspecies chromosomal conjugation is believed responsible for creating the global pathogens Klebsiella pneumoniae ST258 and Escherichia coli ST1193. Interspecies conjugation is also possible but little is known about the genetic architecture or fitness of such hybrids. To study this, we generated by conjugation 14 hybrids of E. coli and Salmonella enterica. These species belong to different genera, diverged from a common ancestor >100 Ma, and share a conserved order of orthologous genes with similar to 15% nucleotide divergence. Genomic analysis revealed that all but one hybrid had acquired a contiguous segment of donor E. coli DNA, replacing a homologous region of recipient Salmonella chromosome, and ranging in size from similar to 100 to >4,000 kb. Recombination joints occurred in sequences with higher-than-average nucleotide identity. Most hybrid strains suffered a large reduction in growth rate, but the magnitude of this cost did not correlate with the length of foreign DNA. Compensatory evolution to ameliorate the cost of low-fitness hybrids pointed towards disruption of complex genetic networks as a cause. Most interestingly, 4 of the 14 hybrids, in which from 45% to 90% of the Salmonella chromosome was replaced with E. coli DNA, showed no significant reduction in growth fitness. These data suggest that the barriers to creating high-fitness interspecies hybrids may be significantly lower than generally appreciated with implications for the creation of novel species.
13.	Bashir, M., et al. (författare) Interactive effect of socioeconomic status and smoking on the risk of allergic and nonallergic asthma among certain occupation groups – Results from two Swedish large adult populations: A Nordic Epilung study 2023 Ingår i: Special Issue: Abstracts from the European Academy of Allergy and Clinical Immunology Hybrid Congress, 1‐3 July 2022. - : John Wiley & Sons. ; , s. 220-220 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
14.	Bergsten, Eva L., 1969-, et al. (författare) Fall and collision related injuries among pedestrians, sickness absence and associations with accident type and occupation 2023 Ingår i: Journal of Safety Research. - : Elsevier. - 0022-4375 .- 1879-1247. ; 86, s. 357-363 Tidskriftsartikel (refereegranskat)abstract Objectives: This study explores pedestrian fall accidents and collisions with other road users in the Swedish road transport system, and sickness absence (SA) in relation to accident type, injury, and occupation. Further, it studies the associations between accident type, occupation, and duration of SA. Methods: Data from several national registers were used that included 15,359 working age pedestrians (20–64 years) receiving healthcare after a fall or collision throughout 2014–2016. Individual characteristics, accident type, injury, and occupation were presented and related to SA. Logistic regression was used to estimate odds ratios (OR), with 95% confidence intervals, for associations between accident type, occupation, and SA duration. Results: About 11,000 pedestrians (72%) were involved in fall accidents in the road traffic environment and well over 4,000 in collisions with another road user; 22% of all injured pedestrians had a new SA. The population had a higher proportion of women and individuals in older age groups (≥45). Of the falls, 31% were due to snow or ice, and these were associated with a higher OR for both short SA (<90 days) 1.76 (95% CI 1.56–1.98) and long SA (≥90 days) 1.81 (95% CI 1.51–2.18), compared to the group slipping, tripping, and stumbling. The working sectors health & social care, and construction had the highest ORs for SA. A higher OR was found for health & social care, short SA 1.58 (95% CI 1.38–1.81), long SA 1.79 (95% CI 1.45–2.20) and for construction, short SA 1.56 (95% CI 1.24–1.96), long SA 1.75 (95% CI 1.26–2.44), compared to the sector finance, communication, & cultural service. Conclusions: The OR for having short and long SA was higher in falls due to snow or ice and differed between occupational sectors. Practical implications: This information contributes to the knowledge base for planning a safe road transport system for pedestrians.
15.	Bergsten, Eva L., 1969-, et al. (författare) Fall and collision related injuries among pedestrians, sickness absence and associations with accident type and occupation 2023 Ingår i: Journal of Safety Research. - : Elsevier. - 0022-4375 .- 1879-1247. ; 86, s. 357-363 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: This study explores pedestrian fall accidents and collisions with other road users in the Swedish road transport system, and sickness absence (SA) in relation to accident type, injury, and occupation. Further, it studies the associations between accident type, occupation, and duration of SA.METHODS: Data from several national registers were used that included 15,359 working age pedestrians (20-64 years) receiving healthcare after a fall or collision throughout 2014-2016. Individual characteristics, accident type, injury, and occupation were presented and related to SA. Logistic regression was used to estimate odds ratios (OR), with 95% confidence intervals, for associations between accident type, occupation, and SA duration.RESULTS: About 11,000 pedestrians (72%) were involved in fall accidents in the road traffic environment and well over 4,000 in collisions with another road user; 22% of all injured pedestrians had a new SA. The population had a higher proportion of women and individuals in older age groups (≥45). Of the falls, 31% were due to snow or ice, and these were associated with a higher OR for both short SA (<90 days) 1.76 (95% CI 1.56-1.98) and long SA (≥90 days) 1.81 (95% CI 1.51-2.18), compared to the group slipping, tripping, and stumbling. The working sectors health & social care, and construction had the highest ORs for SA. A higher OR was found for health & social care, short SA 1.58 (95% CI 1.38-1.81), long SA 1.79 (95% CI 1.45-2.20) and for construction, short SA 1.56 (95% CI 1.24-1.96), long SA 1.75 (95% CI 1.26-2.44), compared to the sector finance, communication, & cultural service.CONCLUSIONS: The OR for having short and long SA was higher in falls due to snow or ice and differed between occupational sectors.PRACTICAL IMPLICATIONS: This information contributes to the knowledge base for planning a safe road transport system for pedestrians.
16.	Biswas, Dhruva, et al. (författare) A clonal expression biomarker associates with lung cancer mortality 2019 Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 25:10, s. 1540-1548 Tidskriftsartikel (refereegranskat)abstract An aim of molecular biomarkers is to stratify patients with cancer into disease subtypes predictive of outcome, improving diagnostic precision beyond clinical descriptors such as tumor stage(1). Transcriptomic intratumor heterogeneity (RNA-ITH) has been shown to confound existing expression-based biomarkers across multiple cancer types(2-6). Here, we analyze multi-region whole-exome and RNA sequencing data for 156 tumor regions from 48 patients enrolled in the TRACERx study to explore and control for RNA-ITH in non-small cell lung cancer. We find that chromosomal instability is a major driver of RNA-ITH, and existing prognostic gene expression signatures are vulnerable to tumor sampling bias. To address this, we identify genes expressed homogeneously within individual tumors that encode expression modules of cancer cell proliferation and are often driven by DNA copy-number gains selected early in tumor evolution. Clonal transcriptomic biomarkers overcome tumor sampling bias, associate with survival independent of clinicopathological risk factors, and may provide a general strategy to refine biomarker design across cancer types.
17.	Brandis, Gerrit, 1985-, et al. (författare) Mutant RNA polymerase can reduce susceptibility to antibiotics via ppGpp-independent induction of a stringent-like response 2021 Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press. - 0305-7453 .- 1460-2091. ; 76:3, s. 606-615 Tidskriftsartikel (refereegranskat)abstract BackgroundMutations in RNA polymerase (RNAP) can reduce susceptibility to ciprofloxacin in Escherichia coli, but the mechanism of transcriptional reprogramming responsible is unknown. Strains carrying ciprofloxacin-resistant (CipR) rpoB mutations have reduced growth fitness and their impact on clinical resistance development is unclear.ObjectivesTo assess the potential for CipRrpoB mutations to contribute to resistance development by estimating the number of distinct alleles. To identify fitness-compensatory mutations that ameliorate the fitness costs of CipRrpoB mutations. To understand how CipRrpoB mutations reprogramme RNAP.MethodsE. coli strains carrying five different CipRrpoB alleles were evolved with selection for improved fitness and characterized for acquired mutations, relative fitness and MICCip. The effects of dksA mutations and a ppGpp0 background on growth and susceptibility phenotypes associated with CipRrpoB alleles were determined.ResultsThe number of distinct CipRrpoB mutations was estimated to be >100. Mutations in RNAP genes and in dksA can compensate for the fitness cost of CipRrpoB mutations. Deletion of dksA reduced the MICCip for strains carrying CipRrpoB alleles. A ppGpp0 phenotype had no effect on drug susceptibility.ConclusionsCipRrpoB mutations induce an ppGpp-independent stringent-like response. Approximately half of the reduction in ciprofloxacin susceptibility is caused by an increased affinity of RNAP to DksA while the other half is independent of DksA. Stringent-like response activating mutations might be the most diverse class of mutations reducing susceptibility to antibiotics.
18.	Cannmo, Patrik, et al. (författare) Stress-Strain Modelling Influenced by Porosities in Cast Aluminium Alloys 2006 Konferensbidrag (refereegranskat)
19.	Chuang, Tzu-Po, et al. (författare) ALK fusion NSCLC oncogenes promote survival and inhibit NK cell responses via SERPINB4 expression 2023 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. ; 120:8 Tidskriftsartikel (refereegranskat)abstract Anaplastic lymphoma kinase (ALK) fusion variants in Non-Small Cell Lung Cancer (NSCLC) consist of numerous dimerizing fusion partners. Retrospective investigations suggest that treatment benefit in response to ALK tyrosine kinase inhibitors (TKIs) differs dependent on the fusion variant present in the patient tumor. Therefore, under -standing the oncogenic signaling networks driven by different ALK fusion variants is important. To do this, we developed controlled inducible cell models expressing either Echinoderm Microtubule Associated Protein Like 4 (EML4)-ALK-V1, EML4-ALK-V3, Kinesin Family Member 5B (KIF5B)-ALK, or TRK-fused gene (TFG)-ALK and investi-gated their transcriptomic and proteomic responses to ALK activity modulation together with patient-derived ALK-positive NSCLC cell lines. This allowed identification of both common and isoform-specific responses downstream of these four ALK fusions. An inflammatory signature that included upregulation of the Serpin B4 serine protease inhibitor was observed in both ALK fusion inducible and patient-derived cells. We show that Signal transducer and activator of transcription 3 (STAT3), Nuclear Factor Kappa B (NF-kappa B) and Activator protein 1 (AP1) are major transcriptional regulators of SERPINB4 downstream of ALK fusions. Upregulation of SERPINB4promotes survival and inhibits natural killer cell-mediated cytotoxicity, which has potential for therapeutic impact targeting the immune response together with ALK TKIs in NSCLC.
20.	Claesson, Elin, 1989, et al. (författare) The primary structural photoresponse of phytochrome proteins captured by a femtosecond X-ray laser 2020 Ingår i: eLife. - 2050-084X. ; 9 Tidskriftsartikel (refereegranskat)abstract Phytochrome proteins control the growth, reproduction, and photosynthesis of plants, fungi, and bacteria. Light is detected by a bilin cofactor, but it remains elusive how this leads to activation of the protein through structural changes. We present serial femtosecond X-ray crystallographic data of the chromophore-binding domains of a bacterial phytochrome at delay times of 1 ps and 10 ps after photoexcitation. The data reveal a twist of the D-ring, which leads to partial detachment of the chromophore from the protein. Unexpectedly, the conserved so-called pyrrole water is photodissociated from the chromophore, concomitant with movement of the A-ring and a key signaling aspartate. The changes are wired together by ultrafast backbone and water movements around the chromophore, channeling them into signal transduction towards the output domains. We suggest that the observed collective changes are important for the phytochrome photoresponse, explaining the earliest steps of how plants, fungi and bacteria sense red light.
21.	Clasen, Joanna L., et al. (författare) Reproductive and hormonal factors and risk of renal cell carcinoma among women in the european prospective investigation into cancer and nutrition 2023 Ingår i: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 12:14, s. 15588-15600 Tidskriftsartikel (refereegranskat)abstract Background: Renal cell carcinoma (RCC) is twice as common among men compared with women, and hormonal factors have been suggested to partially explain this difference. There is currently little evidence on the roles of reproductive and hormonal risk factors in RCC aetiology.Materials & Methods: We investigated associations of age at menarche and age at menopause, pregnancy-related factors, hysterectomy and ovariectomy and exogenous hormone use with RCC risk among 298,042 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.Results: During 15 years of follow-up, 438 RCC cases were identified. Parous women had higher rates of RCC compared with nulliparous women (HR = 1.71, 95% CI 1.18, 2.46), and women who were older at age of first pregnancy had lower rates of RCC (30 years + vs. <20 years HR = 0.53, 95% CI 0.34, 0.82). Additionally, we identified a positive association for hysterectomy (HR = 1.43 95% CI 1.09, 1.86) and bilateral ovariectomy (HR = 1.67, 95% CI 1.13, 2.47), but not unilateral ovariectomy (HR = 0.99, 95% CI 0.61, 1.62) with RCC risk. No clear associations were found for age at menarche, age at menopause or exogenous hormone use.Conclusion: Our results suggest that parity and reproductive organ surgeries may play a role in RCC aetiology.
22.	Cotman, Andrej Emanuel, et al. (författare) Discovery and Hit-to-Lead Optimization of Benzothiazole Scaffold- Based DNA Gyrase Inhibitors with Potent Activity against Acinetobacter baumannii and Pseudomonas aeruginosa 2023 Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 66:2, s. 1380-1425 Tidskriftsartikel (refereegranskat)abstract We have developed compounds with a promising activity against Acinetobacter baumannii and Pseudomonas aerugi-nosa, which are both on the WHO priority list of antibiotic -resistant bacteria. Starting from DNA gyrase inhibitor 1, we identified compound 27, featuring a 10-fold improved aqueous solubility, a 10-fold improved inhibition of topoisomerase IV from A. baumannii and P. aeruginosa, a 10-fold decreased inhibition of human topoisomerase II alpha, and no cross-resistance to novobiocin. Cocrystal structures of 1 in complex with Escherichia coli GyrB24 and (S)-27 in complex with A. baumannii GyrB23 and P. aeruginosa GyrB24 revealed their binding to the ATP-binding pocket of the GyrB subunit. In further optimization steps, solubility, plasma free fraction, and other ADME properties of 27 were improved by fine-tuning of lipophilicity. In particular, analogs of 27 with retained anti-Gram-negative activity and improved plasma free fraction were identified. The series was found to be nongenotoxic, nonmutagenic, devoid of mitochondrial toxicity, and possessed no ion channel liabilities.
23.	da Silva, Marisa, et al. (författare) Cohort profile : The Obesity and Disease Development Sweden (ODDS) study, a pooled cohort 2024 Ingår i: BMJ Open. - 2044-6055. ; 14:7 Tidskriftsartikel (refereegranskat)abstract PURPOSE: The Obesity and Disease Development Sweden (ODDS) study was designed to create a large cohort to study body mass index (BMI), waist circumference (WC) and changes in weight and WC, in relation to morbidity and mortality.PARTICIPANTS: ODDS includes 4 295 859 individuals, 2 165 048 men and 2 130 811 women, in Swedish cohorts and national registers with information on weight assessed once (2 555 098 individuals) or more (1 740 761 individuals), in total constituting 7 733 901 weight assessments at the age of 17-103 years in 1963-2020 (recalled weight as of 1911). Information on WC is available in 152 089 men and 212 658 women, out of whom 108 795 have repeated information on WC (in total 512 273 assessments). Information on morbidity and mortality was retrieved from national registers, with follow-up until the end of 2019-2021, varying between the registers.FINDINGS TO DATE: Among all weight assessments (of which 85% are objectively measured), the median year, age and BMI (IQR) is 1985 (1977-1994) in men and 2001 (1991-2010) in women, age 19 (18-40) years in men and 30 (26-36) years in women and BMI 22.9 (20.9-25.4) kg/m 2 in men and 23.2 (21.2-26.1) kg/m 2 in women. Normal weight (BMI 18.5-24.9 kg/m 2) is present in 67% of assessments in men and 64% in women and obesity (BMI≥30 kg/m 2) in 5% of assessments in men and 10% in women. The median (IQR) follow-up time from the first objectively measured or self-reported current weight assessment until emigration, death or end of follow-up is 31.4 (21.8-40.8) years in men and 19.6 (9.3-29.0) years in women. During follow-up, 283 244 men and 123 457 women died. FUTURE PLANS: The large sample size and long follow-up of the ODDS Study will provide robust results on anthropometric measures in relation to risk of common diseases and causes of deaths, and novel findings in subgroups and rarer outcomes.
24.	Egund, L., et al. (författare) Longitudinal Measurements of FGF23, Sarcopenia, Frailty and Fracture in Older Community Dwelling Women 2023 Ingår i: Journal of Frailty and Aging. - : SERDI. - 2260-1341 .- 2273-4309. ; 12, s. 166-174 Tidskriftsartikel (refereegranskat)abstract Background: FGF23 has been associated with frailty and functional performance in older individuals, but the association to sarcopenia is unknown. Objectives: To investigate the association between FGF23, frailty, sarcopenia and fractures in older community dwelling women. Design: Prospective longitudinal cohort study. Setting: Malmö, Sweden. Participants: 995 75-year-old women, followed prospectively for ten years, with re-investigations after five (n=667) and ten (n=324) years. Measurements: C-terminal levels of FGF23 were measured and a frailty index of ‘deficits in health’ created. Sarcopenia was defined by low muscle mass and strength and “probable sarcopenia” by low muscle mass only. Incident fractures were continuously registered for 10-years. Based on tertiles of FGF23, odds ratio for frailty, sarcopenia and probable sarcopenia was investigated using logistic regression models adjusted for: eGFR, PTH, calcium, vitamin D and phosphate. Fracture-free survival during 10-year follow-up was depicted using Kaplan Meier curves. Results: While fracture-free survival did not differ between tertiles, women in the highest tertile of FGF23 had lower muscle strength and gait speed, and higher proportion with impaired mobility at baseline. At age 75, these women had higher odds of also being frail (ORadj 1.6 (95% CI 1.1–2.4)) and suffering from probable sarcopenia (ORadj 1.8 (95% CI 1.1–3.1)), but not sarcopenia. At follow-up the association between FGF23 and probable sarcopenia was not evident. While the association with frailty was attenuated at age 80 after adjustment (ORadj 1.6 (95% CI 1.0–2.5)), women in the highest tertile had higher odds of being frail at age 85 (ORadj 3.4 (95% CI 1.7–6.6)). Conclusions: FGF23 may be a promising clinical marker for muscle strength, functional performance, and frailty in older women, but not for future fragility fractures. Whether FGF23 is also associated with sarcopenia requires further investigation.
25.	Enander, Karin, 1972-, et al. (författare) Development of peptide-based ratiometric biosensor constructs for direct fluorescence detection of protein analytes 2007 Ingår i: VII European Symposium of the Protein Society,2007. Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
26.	Falck-Ytter, Terje, et al. (författare) The Babytwins Study Sweden (BATSS): A Multi-Method Infant Twin Study of Genetic and Environmental Factors Influencing Infant Brain and Behavioral Development 2021 Ingår i: Twin Research and Human Genetics. - : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 24:4, s. 217-227 Tidskriftsartikel (refereegranskat)abstract Twin studies can help us understand the relative contributions of genes and environment to phenotypic trait variation, including attentional and brain activation measures. In terms of applying methodologies such as electroencephalography (EEG) and eye tracking, which are key methods in developmental neuroscience, infant twin studies are almost nonexistent. Here, we describe the Babytwins Study Sweden (BATSS), a multi-method longitudinal twin study of 177 MZ and 134 DZ twin pairs (i.e., 622 individual infants) covering the 5-36 month time period. The study includes EEG, eye tracking and genetics, together with more traditional measures based on in-person testing, direct observation and questionnaires. The results show that interest in participation in research among twin parents is high, despite the comprehensive protocol. DNA analysis from saliva samples was possible in virtually all participants, allowing for both zygosity confirmation and polygenic score analyses. Combining a longitudinal twin design with advanced technologies in developmental cognitive neuroscience and genomics, BATSS represents a new approach in infancy research, which we hope to have impact across multiple disciplines in the coming years.
27.	Fleming, Cassandra L., et al. (författare) All-photonic kinase inhibitors: light-controlled release-and-report inhibition 2024 Ingår i: CHEMICAL SCIENCE. - 2041-6520 .- 2041-6539. ; 15:18, s. 6897-6905 Tidskriftsartikel (refereegranskat)abstract Light-responsive molecular tools targeting kinases affords one the opportunity to study the underlying cellular function of selected kinases. In efforts to externally control lymphocyte-specific protein tyrosine kinase (LCK) activity, the development of release-and-report LCK inhibitors is described, in which (i) the release of the active kinase inhibitor can be controlled externally with light; and (ii) fluorescence is employed to report both the release and binding of the active kinase inhibitor. This introduces an unprecedented all-photonic method for users to both control and monitor real-time inhibitory activity. A functional cellular assay demonstrated light-mediated LCK inhibition in natural killer cells. The use of coumarin-derived caging groups resulted in rapid cellular uptake and non-specific intracellular localisation, while a BODIPY-derived caging group predominately localised in the cellular membrane. This concept of release-and-report inhibitors has the potential to be extended to other biorelevant targets where both spatiotemporal control in a cellular setting and a reporting mechanism would be beneficial. An all-photonic method is described, in which (i) the release of an active kinase inhibitor is controlled externally with light; and (ii) fluorescence is employed to report both the release and binding of the inhibitor to its corresponding target.
28.	Fontana, Jacopo M., et al. (författare) Ouabain, a Na, K-ATPase ligand, intervenes with the onset of glucose-triggered apoptosis 2015 Ingår i: Molecular Biology of the Cell. - : AMER SOC CELL BIOLOGY. - 1059-1524 .- 1939-4586. ; 26 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
29.	Fransson, Ann-Britt L., et al. (författare) Kinetic Resolution and Chemoenzymatic Dynamic Kinetic Resolution of Functionalized γ-Hydroxy Amides 2005 Ingår i: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 70:7, s. 2582-2587 Tidskriftsartikel (refereegranskat)abstract An efficient kinetic resolution of racemic gamma-hydroxy amides 1 was performed via Pseudomas cepacia lipase (PS-C)-catalyzed transesterification. The enzyme PS-C tolerates both variation in the chain length and different functionalities giving good to high enantioselectivity (E values of up to > 250). The combination of enzymatic kinetic resolution with a ruthenium-catalyzed racemization led to a dynamic kinetic resolution. The use of 2,4-dimethyl-3-pentanol as a hydrogen source to suppress ketone formation in the dynamic kinetic resolution yields the corresponding acetates in good yield and good to high enantioselectivity (ee's up to 98%). The synthetic utility of this procedure was illustrated by the practical synthesis of the versatile intermediate gamma-lactone (R)-5-methyltetrahydrofuran-2-one.
30.	Garoff, Linnéa, et al. (författare) Effect of aminoacyl-tRNA synthetase mutations on susceptibility to ciprofloxacin in Escherichia coli 2018 Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 73:12, s. 3285-3292 Tidskriftsartikel (refereegranskat)abstract Background: Chromosomal mutations that reduce ciprofloxacin susceptibility in Escherichia coli characteristically map to drug target genes (gyrAB and parCE), and genes encoding regulators of the AcrAB-TolC efflux pump. Mutations in RNA polymerase can also reduce susceptibility, by up-regulating the MdtK efflux pump.Objectives: We asked whether mutations in additional chromosomal gene classes could reduce susceptibility to ciprofloxacin.Methods: Experimental evolution, complemented by WGS analysis, was used to select and identify mutations that reduce susceptibility to ciprofloxacin. Transcriptome analysis, genetic reconstructions, susceptibility measurements and competition assays were used to identify significant genes and explore the mechanism of resistance.Results: Mutations in three different aminoacyl-tRNA synthetase genes (leuS, aspS and thrS) were shown to re- duce susceptibility to ciprofloxacin. For two of the genes (leuS and aspS) the mechanism was partially dependent on RelA activity. Two independently selected mutations in leuS (Asp162Asn and Ser496Pro) were studied in most detail, revealing that they induce transcriptome changes similar to a stringent response, including up-regulation of three efflux-associated loci (mdtK, acrZ and ydhJK). Genetic analysis showed that reduced susceptibility depended on the activity of these loci. Broader antimicrobial susceptibility testing showed that the leuS mutations also reduce susceptibility to additional classes of antibiotics chloramphenicol, rifampicin, mecillinam, ampicillin and trimethoprim).Conclusions: The identification of mutations in multiple tRNA synthetase genes that reduce susceptibility to ciprofloxacin and other antibiotics reveals the existence of a large mutational target that could contribute to re- sistance development by up-regulation of an array of efflux pumps.
31.	Garoff, Linnéa, et al. (författare) Population Bottlenecks Strongly Influence the Evolutionary Trajectory to Fluoroquinolone Resistance in Escherichia coli 2020 Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 37:6, s. 1637-1646 Tidskriftsartikel (refereegranskat)abstract Experimental evolution is a powerful tool to study genetic trajectories to antibiotic resistance under selection. A confounding factor is that outcomes may be heavily influenced by the choice of experimental parameters. For practical purposes (minimizing culture volumes), most experimental evolution studies with bacteria use transmission bottleneck sizes of 5 x 10(6) cfu. We currently have a poor understanding of how the choice of transmission bottleneck size affects the accumulation of deleterious versus high-fitness mutations when resistance requires multiple mutations, and how this relates outcome to clinical resistance. We addressed this using experimental evolution of resistance to ciprofloxacin in Escherichia coli. Populations were passaged with three different transmission bottlenecks, including single cell (to maximize genetic drift) and bottlenecks spanning the reciprocal of the frequency of drug target mutations (10(8) and 10(10)). The 10(10) bottlenecks selected overwhelmingly mutations in drug target genes, and the resulting genotypes corresponded closely to those found in resistant clinical isolates. In contrast, both the 10(8) and single-cell bottlenecks selected mutations in three different gene classes: 1) drug targets, 2) efflux pump repressors, and 3) transcription-translation genes, including many mutations with low fitness. Accordingly, bottlenecks smaller than the average nucleotide substitution rate significantly altered the experimental outcome away from genotypes observed in resistant clinical isolates. These data could be applied in designing experimental evolution studies to increase their predictive power and to explore the interplay between different environmental conditions, where transmission bottlenecks might vary, and resulting evolutionary trajectories.
32.	Gimeno, David, et al. (författare) Cross-national comparisons of sickness absence systems and statistics : towards common indicators 2014 Ingår i: European Journal of Public Health. - : Oxford University Press. - 1101-1262 .- 1464-360X. ; 24:4, s. 663-666 Tidskriftsartikel (refereegranskat)abstract We aimed to identify common elements in work sickness absence (SA) in Spain, Sweden and The Netherlands. We estimated basic statistics on benefits eligibility, SA incidence and duration and distribution by major diagnostics. The three countries offer SA benefits for at least 12 months and wage replacement, differing in who and when the payer assumes responsibility; the national health systems provide health care with participation from occupational health services. Episodes per 1000 salaried workers and episode duration varied by country; their distribution by diagnostic was similar. Basic and useful SA indicators can be constructed to facilitate cross-country comparisons.
33.	Graham, Emelie Linnéa, 1989- (författare) Insights into key processes governing atmospheric aerosol loadings and their interactions with clouds 2022 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Aerosol particles are ubiquitous in the atmosphere and an essential part of the atmospheric radiation balance regulating the Earth’s temperature. Aerosol-cloud interaction still remains the largest single uncertainty in future climate projections. In addition, aerosols are also responsible for air pollution, causing severe health effects. With various origins and short atmospheric lifetimes, aerosols are unevenly distributed in the atmosphere, making simulations of air pollution and future climate scenarios challenging. This thesis aims to improve the understanding of the physical and chemical processes that govern aerosol concentration in the atmosphere, using both field as well as laboratory experiments.Field measurements were performed at a remote station at Mt Åreskutan, central Sweden. Located at 1250 m a.s.l. the station is frequently covered by clouds, allowing for in-cloud measurements. Aerosol particle size distribution measurements revealed a shift towards smaller diameters in the ambient aerosol size distribution after the station had been within a cloud. This is a result of the larger (> 60 nm) particles being more effectively scavenged by clouds as compared with the smaller end of the size distribution. Chemical analysis revealed a similar composition of the cloud water as the particulate matter, suggesting that cloud droplet activation at Mt Åreskutan is primarily dependent on particle size, and the aerosol population to have been internally mixed. Similarly, measurement of hygroscopicity and volatility revealed similar water-solubility and evaporation behaviour for the ambient aerosols and cloud residuals, with the organic fraction representative of aged boreal secondary organic aerosol (SOA) and showing no signs of significant aqueous phase processing.The NArVE laboratory campaign took place in an atmospheric simulation chamber at Paul Scherrer Institute, Switzerland. The experiments traced nitrate-induced SOA formation and ageing of three biogenic precursors, namely α-pinene, isoprene, and β-caryophyllene, using mass spectrometric techniques and evaporation measurements. The volatility of α-pinene SOA from nitrate oxidation was found to be higher than the corresponding ozonolysis products. The nitrate oxidation of isoprene resulted in species with similar volatility to α-pinene, while the β-caryophyllene system produced lower volatility compounds then the other two precursors. Quantitative comparison of the volatility measurements to commonly-used theoretical parameterizations revealed the need for further studies of the impact of the nitrate functional group on molecular volatility. Dark ageing of α-pinene was found to mainly occur through particle phase oxidation forming less volatile species. During the photolysis related to sunrise the molecular composition changed towards more volatile species, while no significant evaporation could be observed for the α-pinene and isoprene systems.A common theme in all these studies was investigating the level of detail needed to theoretically describe the observations. We found that while simple approximations (such as internal mixing and size-independent chemical composition of the particles) are often sufficient to capture trends in atmospheric aerosol properties, more research on (1) the processes taking place on shorter time- and smaller size scales than investigated here and (2) the effects of nitrate group on molecular volatility are warranted.
34.	Graham, Emelie Linnéa, et al. (författare) Physical and chemical properties of aerosol particles and cloud residuals on Mt. angstrom reskutan in Central Sweden during summer 2014 2020 Ingår i: Tellus. Series B, Chemical and physical meteorology. - : Stockholm University Press. - 0280-6509 .- 1600-0889. ; 72:1 Tidskriftsartikel (refereegranskat)abstract The size distribution, volatility and hygroscopicity of ambient aerosols and cloud residuals were measured with a differential mobility particle sizer (DMPS) and a volatility-hygroscopicity tandem differential mobility analyser (VHTDMA) coupled to a counterflow virtual impactor (CVI) inlet during the Cloud and Aerosol Experiment at Are (CAEsAR) campaign at Mt. Areskutan during summer 2014. The chemical composition of particulate matter (PM) and cloud water were analysed offline using thermo-optical OC/EC analysis and ion chromatography. The importance of aerosol particle size for cloud droplet activation and subsequent particle scavenging was clearly visible in the measured size distributions. Cloud residuals were shifted towards larger sizes compared to ambient aerosol, and the cloud events were followed by a size distribution dominated by smaller particles. Organics dominated both PM (62% organic mass fraction) and cloud water (63% organic mass fraction) composition. The volatility and hygroscopicity of the ambient aerosols were representative of homogeneous aged aerosol with contributions from biogenic secondary organics, with median volume fraction remaining (VFR) of 0.04-0.05, and median hygroscopicity parameter kappa of 0.16-0.24 for 100-300 nm particles. The corresponding VFR and kappa for the cloud residuals were 0.03-0.04 and 0.18-0.20. The chemical composition, hygroscopicity and volatility measurements thus showed no major differences between the ambient aerosol particles and cloud residuals. The VFR and kappa values predicted based on the chemical composition measurements agreed well with the VHTDMA measurements, indicating the bulk chemical composition to be a reasonable approximation throughout the size distribution. There were indications, however, of some more subtle changes in time scales not achievable by the offline chemical analysis applied here. Further, online observations of aerosol and cloud residual chemical composition are therefore warranted.
35.	Hansson, Caroline, 1981, et al. (författare) Influence of ghrelin on the central serotonergic signaling system in mice 2014 Ingår i: Neuropharmacology. - : Elsevier BV. - 0028-3908. ; 79, s. 498-505 Tidskriftsartikel (refereegranskat)abstract The central ghrelin signaling system engages key pathways of importance for feeding control, recently shown to include those engaged in anxiety-like behavior in rodents. Here we sought to determine whether ghrelin impacts on the central serotonin system, which has an important role in anxiety. We focused on two brain areas, the amygdala (of importance for the mediation of fear and anxiety) and the dorsal raphe (i.e. the site of origin of major afferent serotonin pathways, including those that project to the amygdala). In these brain areas, we measured serotonergic turnover (using HPLC) and the mRNA expression of a number of serotonin-related genes (using real-time PCR). We found that acute central administration of ghrelin to mice increased the serotonergic turnover in the amygdala. It also increased the mRNA expression of a number of serotonin receptors, both in the amygdala and in the dorsal raphe. Studies in ghrelin receptor (GHS-R1A) knock-out mice showed a decreased mRNA expression of serotonergic receptors in both the amygdala and the dorsal raphe, relative to their wild-type littermates. We conclude that the central serotonin system is a target for ghrelin, providing a candidate neurochemical substrate of importance for ghrelin's effects on mood. © 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
36.	Hedman, Linnea, 1979-, et al. (författare) Electronic cigarette use and smoking cessation in cohort studies and randomized trials: A systematic review and meta-analysis 2021 Ingår i: Tobacco Prevention & Cessation. - : E.U. European Publishing. - 2459-3087. ; 7 Tidskriftsartikel (refereegranskat)abstract INTRODUCTION The aim of this systematic review and meta-analysis was to assess the association between e-cigarette use and subsequent smoking cessation in cohort studies and randomized controlled trials (RCT). METHODS A systematic literature search was finalized 11 November 2019 using EMBASE, Cochrane Library, Scopus, PubMed Health, NICE evidence search, PROSPERO, CRD, PsycInfo, and PubMed including Medline. Inclusion criteria were: reporting empirical results; longitudinal observational design with a minimum of 3 months of follow-up; including general population samples; and allowing for comparison between users and non-users of e-cigarettes. Studies rated as having high risk of bias were excluded. The procedures described by PRISMA were followed, and the quality of evidence was rated using GRADE. RESULTS Twenty-eight longitudinal, peer-reviewed publications from 26 cohort studies, and eight publications from seven RCTs assessing the association between e-cigarette use and smoking cessation were included in this review. A random-effects meta-analysis based on 39147 participants in cohort studies showed a pooled unadjusted odds ratio (OR) for smoking cessation among baseline e-cigarette users compared with baseline non-users of 0.97 (95% CI: 0.67-1.40), while the adjusted OR was 0.90 (95% CI: 0.63-1.27). The pooled odds ratio for smoking cessation in RCTs was 1.78 (95% CI: 1.41-2.25). The evidence for cohort studies was graded as very low and for RCTs as low. CONCLUSIONS We did not find quality evidence for an association between e-cigarette use and smoking cessation. Although RCTs tended to support a more positive association between e-cigarette use and smoking cessation than the cohort studies, the grading of evidence was consistently low.
37.	Henneberger, P K, et al. (författare) The occupational contribution to severe exacerbation of asthma. 2010 Ingår i: The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 36:4, s. 743-50 Tidskriftsartikel (refereegranskat)abstract The goal of this study was to identify occupational risk factors for severe exacerbation of asthma and estimate the extent to which occupation contributes to these events. The 966 participants were working adults with current asthma who participated in the follow-up phase of the European Community Respiratory Health Survey. Severe exacerbation of asthma was defined as self-reported unplanned care for asthma in the past 12 months. Occupations held in the same period were combined with a general population job-exposure matrix to assess occupational exposures. 74 participants reported having had at least one severe exacerbation event, for a 1-yr cumulative incidence of 7.7%. From regression models that controlled for confounders, the relative risk (RR) was statistically significant for low (RR 1.7, 95% CI 1.1-2.6) and high (RR 3.6, 95% CI 2.2-5.8) biological dust exposure, high mineral dust exposure (RR 1.8, 95% CI 1.02-3.2), and high gas and fumes exposure (RR 2.5, 95% CI 1.2-5.5). The summary category of high dust, gas, or fumes exposure had RR 3.1 (95% CI 1.9-5.1). Based on this RR, the population attributable risk was 14.7% among workers with current asthma. These results suggest occupation contributes to approximately one in seven cases of severe exacerbation of asthma in a working population, and various agents play a role.
38.	Hua, Xing, et al. (författare) Selective Serotonin Reuptake Inhibitors for Stroke Recovery 2022 Ingår i: Stroke. - : Lippincott Williams & Wilkins. - 0039-2499 .- 1524-4628. ; 53:9, s. E426-E428 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
39.	Huseby, Douglas L., et al. (författare) Mutation supply and relative fitness shape the genotypes of ciprofloxacin-resistant Escherichia coli 2017 Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 34:5, s. 1029-1039 Tidskriftsartikel (refereegranskat)abstract Ciprofloxacin is an important antibacterial drug targeting Type II topoisomerases, highly active against Gram-negatives including Escherichia coli. The evolution of resistance to ciprofloxacin in E. coli always requires multiple genetic changes, usually including mutations affecting two different drug target genes, gyrA and parC. Resistant mutants selected in vitro or in vivo can have many different mutations in target genes and efflux regulator genes that contribute to resistance. Among resistant clinical isolates the genotype, gyrA S83L D87N, parC S80I is significantly overrepresented suggesting that it has a selective advantage. However, the evolutionary or functional significance of this high frequency resistance genotype is not fully understood. By combining experimental data and mathematical modeling, we addressed the reasons for the predominance of this specific genotype. The experimental data were used to model trajectories of mutational resistance evolution under different conditions of drug exposure and population bottlenecks. We identified the order in which specific mutations are selected in the clinical genotype, showed that the high frequency genotype could be selected over a range of drug selective pressures, and was strongly influenced by the relative fitness of alternative mutations and factors affecting mutation supply. Our data map for the first time the fitness landscape that constrains the evolutionary trajectories taken during the development of clinical resistance to ciprofloxacin and explain the predominance of the most frequently selected genotype. This study provides strong support for the use of in vitro competition assays as a tool to trace evolutionary trajectories, not only in the antibiotic resistance field.
40.	Huusko, Linnea L., et al. (författare) Stronger Response to the Aerosol Indirect Effect Due To Cooling in Remote Regions 2022 Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 49:21 Tidskriftsartikel (refereegranskat)abstract It is often assumed that effective radiative forcings, regardless of forcing agent, are additive in the temperature change. Using climate model simulations with abruptly applied aerosol forcing we find that the temperature response per unit forcing is larger if induced by aerosol-cloud interactions than directly by aerosols. The spatial patterns of forcing and temperature change show that aerosol-cloud interactions induce cooling over remote oceans in the extratropics, whereas the effect of increased emissions is localized around the emission sources primarily over tropical land. The results are consistent with ideas of how the patterns of sea surface temperature impact radiative feedbacks, and a large forcing efficacy of aerosol-cloud interactions could help explain previously observed intermodel spread in the response to aerosols.
41.	Ihalainen, J. A., et al. (författare) Chromophore-Protein Interplay during the Phytochrome Photocycle Revealed by Step-Scan FTIR Spectroscopy 2018 Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 140:39, s. 12396-12404 Tidskriftsartikel (refereegranskat)abstract Phytochrome proteins regulate many photo-responses of plants and microorganisms. Light absorption causes isomerization of the biliverdin chromophore, which triggers a series of structural changes to activate the signaling domains of the protein. However, the structural changes are elusive, and therefore the molecular mechanism of signal transduction remains poorly understood. Here, we apply twocolor step-scan infrared spectroscopy to the bacteriophytochrome from Deinococcus radiodurans. We show by recordings in H2O and D2O that the hydrogen bonds to the biliverdin D-ring carbonyl become disordered in the first intermediate (Lumi-R) forming a dynamic microenvironment, then completely detach in the second intermediate (Meta-R), and finally reform in the signaling state (Pfr). The spectra reveal via isotope labeling that the refolding of the conserved "PHY-tongue" region occurs with the last transition between Meta-R and Pfr. Additional changes in the protein backbone are detected already within microseconds in Lumi-R Aided by molecular dynamics simulations, we find that a strictly conserved salt bridge between an arginine of the PHY tongue and an aspartate of the chromophore binding domains is broken in Lumi-R and the arginine is recruited to the D-ring C=O. This rationalizes how isomerization of the chromophore is linked to the global structural rearrangement in the sensory receptor. Our findings advance the structural understanding of phytochrome photoactivation.
42.	Islam, Tohidul, et al. (författare) Apolipoprotein E impairs amyloid-β fibril elongation and maturation 2020 Ingår i: The FEBS Journal. - : Wiley-Blackwell. - 1742-464X .- 1742-4658. ; 287:6, s. 1208-1219 Tidskriftsartikel (refereegranskat)abstract Alzheimer's disease (AD) is strongly linked to amyloid depositions of the Aβ peptide (Aβ). The lipid-binding protein apolipoprotein E (ApoE) has been found to interfere with Aβ amyloid formation and to exert a strong clinical impact to the pathology of AD. The APOE gene exists in three allelic isoforms represented by APOE ε2, APOE ε3, and APOE ε4. Carriers of the APOE ε4 variant display a gene dose-dependent increased risk of developing the disease. Aβ amyloids are formed via a nucleation-dependent mechanism where free monomers are added onto a nucleus in a template-dependent manner. Using a combination of surface plasmon resonance and thioflavin-T assays, we here show that ApoE can target the process of fibril elongation and that its interference effectively prevents amyloid maturation. We expose a complex equilibrium where the concentration of ApoE, Aβ monomers, and the amount of already formed Aβ fibrils will affect the relative proportion and formation rate of mature amyloids versus alternative assemblies. The result illustrates a mechanism which may affect both the clearance rate of Aβ assemblies in vivo and the population of cytotoxic Aβ assemblies.
43.	Jarnac, Amelie, et al. (författare) Compression of TW class laser pulses in a planar hollow waveguide for applications in strong-field physics 2014 Ingår i: European Physical Journal D. Atomic, Molecular, Optical and Plasma Physics. - : Springer Science and Business Media LLC. - 1434-6060. ; 68:12 Tidskriftsartikel (refereegranskat)abstract We demonstrate pulse post-compression of a TW class chirped pulse amplification laser employing a gas-filled planar hollow waveguide. A waveguide throughput of 80% is achieved for 50 mJ input pulse energy. Good focusability is found and after compression with chirped mirrors a pulse duration of sub-15 fs is measured in the beam center. Whereas a total energy efficiency of approximate to 70% should be achievable, our post-compressor currently delivers 20 mJ output pulse energy (approximate to 40% efficiency), mostly limited by apertures of chirped mirrors and vacuum windows. The viability of the planar hollow waveguide compression scheme for applications in strong-field physics is demonstrated by generating high-order harmonics in a pulsed Ar gas cell.
44.	Jarvis, Erich D., et al. (författare) Whole-genome analyses resolve early branches in the tree of life of modern birds 2014 Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 346:6215, s. 1320-1331 Tidskriftsartikel (refereegranskat)abstract To better determine the history of modern birds, we performed a genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves using phylogenomic methods created to handle genome-scale data. We recovered a highly resolved tree that confirms previously controversial sister or close relationships. We identified the first divergence in Neoaves, two groups we named Passerea and Columbea, representing independent lineages of diverse and convergently evolved land and water bird species. Among Passerea, we infer the common ancestor of core landbirds to have been an apex predator and confirm independent gains of vocal learning. Among Columbea, we identify pigeons and flamingoes as belonging to sister clades. Even with whole genomes, some of the earliest branches in Neoaves proved challenging to resolve, which was best explained by massive protein-coding sequence convergence and high levels of incomplete lineage sorting that occurred during a rapid radiation after the Cretaceous-Paleogene mass extinction event about 66 million years ago.
45.	Karlsson-Lindahl, Linda, 1972, et al. (författare) Heparanase affects food intake and regulates energy balance in mice. 2012 Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:3 Tidskriftsartikel (refereegranskat)abstract Mutation of the melanocortin-receptor 4 (MC4R) is the most frequent cause of severe obesity in humans. Binding of agouti-related peptide (AgRP) to MC4R involves the co-receptor syndecan-3, a heparan sulfate proteoglycan. The proteoglycan can be structurally modified by the enzyme heparanase. Here we tested the hypothesis that heparanase plays a role in food intake behaviour and energy balance regulation by analysing body weight, body composition and food intake in genetically modified mice that either lack or overexpress heparanase. We also assessed food intake and body weight following acute central intracerebroventricular administration of heparanase; such treatment reduced food intake in wildtype mice, an effect that was abolished in mice lacking MC4R. By contrast, heparanase knockout mice on a high-fat diet showed increased food intake and maturity-onset obesity, with up to a 40% increase in body fat. Mice overexpressing heparanase displayed essentially the opposite phenotypes, with a reduced fat mass. These results implicate heparanase in energy balance control via the central melanocortin system. Our data indicate that heparanase acts as a negative modulator of AgRP signaling at MC4R, through cleavage of heparan sulfate chains presumably linked to syndecan-3.
46.	Kjeldgård, Linnea, 1985-, et al. (författare) Diagnosis-specific sickness absence among injured working-aged pedestrians: a sequence analysis 2023 Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 23:1, s. 367- Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The knowledge about the long-term consequences in terms of sickness absence (SA) among pedestrians injured in a traffic-related accident, including falls, is scarce. Therefore, the aim was to explore diagnosis-specific patterns of SA during a four-year period and their association with different sociodemographic and occupational factors among all individuals of working ages who were injured as a pedestrian. METHODS: A nationwide register-based study, including all individuals aged 20-59 and living in Sweden, who in 2014-2016 had in- or specialized outpatient healthcare after a new traffic-related accident as a pedestrian. Diagnosis-specific SA (> 14 days) was assessed weekly from one year before the accident up until three years after the accident. Sequence analysis was used to identify patterns (sequences) of SA, and cluster analysis to form clusters of individuals with similar sequences. Odds ratios (ORs) with 95% confidence intervals (CIs) for association of the different factors and cluster memberships were estimated by multinomial logistic regression. RESULTS: In total, 11,432 pedestrians received healthcare due to a traffic-related accident. Eight clusters of SA patterns were identified. The largest cluster was characterized by no SA, three clusters had different SA patterns due to injury diagnoses (immediate, episodic, and later). One cluster had SA both due to injury and other diagnoses. Two clusters had SA due to other diagnoses (short-term and long-term) and one cluster mainly consisted of individuals with disability pension (DP). Compared to the cluster "No SA", all other clusters were associated with older age, no university education, having been hospitalized, and working in health and social care. The clusters "Immediate SA", "Episodic SA" and "Both SA due to injury and other diagnoses" were also associated with higher odds of pedestrians who sustained a fracture. CONCLUSIONS: This nationwide study of the working-aged pedestrians observed diverging patterns of SA after their accident. The largest cluster of pedestrians had no SA, and the other seven clusters had different patterns of SA in terms of diagnosis (injury and other diagnoses) and timing of SA. Differences were found between all clusters regarding sociodemographic and occupational factors. This information can contribute to the understanding of long-term consequences of road traffic accidents.
47.	Köhnke, Rickard, et al. (författare) Feeding appetite suppressing thylakoids to pigs alters pancreatic lipase/colipase secretion 2010 Ingår i: Livestock Science. - : Elsevier BV. - 1871-1413. ; 134:1-3, s. 68-71 Konferensbidrag (refereegranskat)abstract The mechanism for a new appetite suppressor named thylakoids (membrane proteins derived from spinach leaves) was examined in vivo in pigs. Thylakoids inhibit the lipase/colipase hydrolysis of triacylglycerols (TG) in vitro and suppress food intake, decrease body weight gain and raise the circulating satiety hormone cholecystokinin (CCK) in rats but its mechanism in vivo remains unclear. We hypothesized that a thylakoid-enriched diet prolongs intestinal digestion of food and therefore promote satiety signaling. Five pigs were surgically prepared with a fistula in the duodenum for collection of digesta and with two catheters, one in v. jugularis and one in v. porta, for blood collection. After 1 week of recovery and an overnight fast the pigs were fed a high-fat diet with and without supplementation with thylakoids. Duodenal content and blood samples were taken before and 15, 30, 60, 120, 240 and 360 min after feeding. Pancreatic lipase and colipase enzymes were measured in duodenal digesta. Blood samples were analyzed for the satiety hormone CCK as well as insulin and glucose. We found that pancreatic lipase/colipase level increased and stayed elevated for a longer time in the duodenum in the pigs receiving thylakoids compared to the control. CCK levels were unchanged. Insulin levels were significantly reduced by the thylakoid treatment without any change in blood glucose. In conclusion, thylakoids increased lipase/colipase secretion. The mechanism for this secretion appears not to be related to CCK and may be an effect of vagal activation. Thylakoids gave reduced insulin levels without any change in glucose levels. (C) 2010 Published by Elsevier B.V.
48.	Lind, M. L., et al. (författare) Incidence of hand eczema in female Swedish hairdressers 2007 Ingår i: Occup Environ Med. - : BMJ. - 1470-7926 .- 1351-0711. ; 64:3, s. 191-5 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: To estimate the occurrence of hand eczema in hairdressers in Sweden. METHODS: The occurrence of hand eczema was estimated in a Swedish longitudinal retrospective cohort study including all female graduates from vocational schools for hairdressers from 1970 to 1995. A stratified sample from the general population acted as controls. A self-administered questionnaire including questions on the occurrence of hand eczema, skin atopy, working periods and number of hair treatments performed per week was sent to the participants. Incidence rate ratios (IRRs) of hand eczema were estimated. RESULTS: The incidence rate of hand eczema in hairdressers was 23.8 cases/1000 person-years, whereas in hairdressers who were aged <25 years it was 37.1/1000 person-years. The corresponding IRR for hairdressers compared with controls was 2.5 (95% confidence interval (CI) 2.2 to 2.8), and that for younger hairdressers was 3.1 (95% CI 2.6 to 3.5). The mean age at onset of hand eczema was 21.6 years for hairdressers and 21.2 years for controls. The 1-year prevalence of hand eczema was 18.0% for hairdressers and 12.1% for controls. A large number of hair treatments involving exposure to skin irritants and sensitisers were reported. The incidence rate of hand eczema was higher among individuals with a history of childhood eczema, both for hairdressers and for controls, giving an (age-adjusted) IRR of 1.9 and 2.2, respectively. The attributable fraction of hand eczema from skin atopy was 9.6%. A synergistic effect of skin atopy and hairdressing was found on the occurrence of hand eczema. The relative excess risk due to interaction was 1.21 (95% CI 0.21 to 2.21; p = 0.01). CONCLUSION: Hairdressers are highly exposed to skin-damaging substances. The self-reported incidence of hand eczema was substantially higher in female hairdressers than in controls from the general population and than that found previously in register-based studies. For many individuals, onset of hand eczema occurs early in life. Only about 10% of the hand eczema cases among hairdressers would be prevented if no one with skin atopy entered the trade.
49.	Lindberg, Anne, et al. (författare) Subjects with COPD and productive cough have an increased risk for exacerbations and death 2015 Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 109:1, s. 88-95 Tidskriftsartikel (refereegranskat)abstract Background: Chronic bronchitis is related to worse general health status, exacerbations and mortality among subjects with COPD. Also less longstanding cough and phlegm may be related to worse prognosis in COPD but this has rarely been evaluated in population-based studies. Aim: To evaluate the relationship between productive cough, exacerbations and mortality among subjects with and without COPD. Method: All subjects with COPD (n = 993) were identified together with sex-and age matched reference subjects without obstructive lung function impairment from four population-based cohorts in 2002-04. Baseline spirometry and structured interview including data on exacerbations last 12 months were used in this study (n = 1986) together with mortality data collected until February 2012. Results: Productive cough was more common in COPD than non-COPD (42.8 vs. 23.5%, p < 0.001), more common in men than women, but associated to exacerbations in both sexes. COPD-subjects with productive cough had the highest risk for exacerbations in both sexes and they had a significantly increased risk for death (HR 1.48, 95% CI 1.13-1.94) also when adjusted for sex, age, BMI, smoking habits and heart disease. Conclusion: Productive cough was common and increased the risk for exacerbations in both sexes, in both COPD and non-COPD. COPD-subjects with productive cough had the highest risk for exacerbations and a significantly higher risk for death also after adjustment for common risk factors. (C) 2014 Elsevier Ltd. All rights reserved.
50.	Mboya, Innocent B, et al. (författare) Time trends of the association of body mass index with mortality in 3.5 million young Swedish adults Ingår i: Annals of Epidemiology. - 1047-2797. ; 97, s. 23-32 Tidskriftsartikel (refereegranskat)abstract PURPOSE: We investigated time trends of the obesity-mortality association, accounting for age, sex, and cause-specific deaths.METHODS: We analysed pooled nationwide data in Sweden for 3,472,310 individuals aged 17-39 years at baseline in 1963-2016. Cox regression and flexible parametric survival models investigated BMI-mortality associations in sub-groups of sex and baseline calendar years (men: <1975, 1975-1985, ≥1985 and women: <1985, 1985-1994, ≥1995).RESULTS: Comparing men with obesity vs. normal weight, all-cause and "other-cause" mortality associations decreased over periods; HR (95% CI) 1.92 (1.83-2.01) and 1.70 (1.58-1.82) for all-cause and 1.72 (1.58-1.87) and 1.40 (1.28-1.53) for "other-cause" mortality in <1975 and ≥1985, but increased for CVD mortality; HR 2.71 (2.51-2.94) and 3.91 (3.37-4.53). Higher age at death before 1975 coincided with more obesity-related deaths at higher ages. Furthermore, the all-cause mortality association for different ages in men showed no clear differences between periods (p-interaction=0.09), suggesting no calendar effect after accounting for attained age. Similar, but less pronounced, results were observed in women. Associations with cancer mortality showed no clear trends in men or in women.CONCLUSIONS: Accounting for differences in age and death causes between calendar periods when investigating BMI-mortality time trends may avoid misinterpreting the risks associated with obesity over time.

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