| 1. |
- Hammarström, Anne, et al.
(författare)
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Why does youth unemployment lead to scarring of depressive symptoms in adulthood? The importance of early adulthood drinking
- 2023
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Ingår i: Scandinavian Journal of Public Health. - : Sage Publications. - 1403-4948 .- 1651-1905.
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim of the paper is to analyse if alcohol consumption could explain the scarring effect of youth unemployment on later depressive symptoms.Methods: The analyses are based on the 24-year follow-up of school leavers in a municipality in Northern Sweden (the Northern Swedish Cohort). Four-way decomposition analyses were performed to analyse if alcohol use at age 30 years could mediate and/or moderate the effect of youth unemployment (ages 18/21 years) on depressive symptoms in later adulthood (age 43 years).Results: Excessive alcohol use at early adulthood (age 30 years) mediates 18% of the scarring effect of youth unemployment on depressive symptoms in later adulthood. The scarring effect was seen among both those with and without excessive alcohol use.Conclusions: Youth unemployment leads to poor mental health later in life and part of these relations are explained by excessive alcohol consumption in early adulthood. Policy interventions should target the prevention of youth unemployment for reaching a lower alcohol consumption and better mental health.
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| 2. |
- Hueting, David A., et al.
(författare)
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Design, structure and plasma binding of ancestral β-CoV scaffold antigens
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- We report the application of ancestral sequence reconstruction on coronavirus spike protein, resulting in stable and highly soluble ancestral scaffold antigens (AnSAs). The AnSAs interact with plasma of patients recovered from COVID-19 but do not bind to the human angiotensin-converting enzyme 2 (ACE2) receptor. Cryo-EM analysis of the AnSAs yield high resolution structures (2.6–2.8 Å) indicating a closed pre-fusion conformation in which all three receptor-binding domains (RBDs) are facing downwards. The structures reveal an intricate hydrogen-bonding network mediated by well-resolved loops, both within and across monomers, tethering the N-terminal domain and RBD together. We show that AnSA-5 can induce and boost a broad-spectrum immune response against the wild-type RBD as well as circulating variants of concern in an immune organoid model derived from tonsils. Finally, we highlight how AnSAs are potent scaffolds by replacing the ancestral RBD with the wild-type sequence, which restores ACE2 binding and increases the interaction with convalescent plasma.
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| 3. |
- Abrahamsson, Maria, et al.
(författare)
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Steric influence on the excited-state lifetimes of ruthenium complexes with bipyridyl-alkanylene-pyridyl ligands.
- 2008
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Ingår i: Inorganic Chemistry. - : ACS. - 0020-1669 .- 1520-510X. ; 47:9, s. 3540-3548
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Tidskriftsartikel (refereegranskat)abstract
- The structural effect on the metal-to-ligand charge transfer (MLCT) excited-state lifetime has been investigated in bis-tridentate Ru(II)-polypyridyl complexes based on the terpyridine-like ligands [6-(2,2'-bipyridyl)](2-pyridyl)methane (1) and 2-[6-(2,2'-bipyridyl)]-2-(2-pyridyl)propane (2). A homoleptic ([Ru(2)(2)](2+)) and a heteroleptic complex ([Ru(ttpy)(2)](2+)) based on the new ligand 2 have been prepared and their photophysical and structural properties studied experimentally and theoretically and compared to the results for the previously reported [Ru(1)(2)](2+). The excited-state lifetime of the homoleptic Ru-II complex with the isopropylene-bridged ligand 2 was found to be 50 times shorter than that of the corresponding homoleptic Ru-II complex of ligand 1, containing a methylene bridge. A comparison of the ground-state geometries of the two homoleptic complexes shows that steric interactions involving the isopropylene bridges make the coordination to the central Ru-II ion less octahedral in [Ru(2)(2)](2+) than in [Ru(1)(2))(2+). Calculations indicate that the structural differences in these complexes influence their ligand field splittings as well as the relative stabilities of the triplet metal-to-ligand charge transfer ((MLCT)-M-3) and metal-centered ((MC)-M-3) excited states. The large difference in measured excited-state lifetimes for the two homoleptic Ru-II complexes is attributed to a strong influence of steric interactions on the ligand field strength, which in turn affects the activation barriers for thermal conversion from (MLCT)-M-3 states to short-lived (MC)-M-3 states.
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| 4. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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| 5. |
- Gustafsson, Per E., et al.
(författare)
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Do peer relations in adolescence influence health in adulthood? : Peer problems in the school setting and the metabolic syndrome in middle-age
- 2012
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Ingår i: PLOS ONE. - San Francisco : Public Library of Science. - 1932-6203. ; 7:6, s. e39385-
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Tidskriftsartikel (refereegranskat)abstract
- While the importance of social relations for health has been demonstrated in childhood, adolescence and adulthood, few studies have examined the prospective importance of peer relations for adult health. The aim of this study was to examine whether peer problems in the school setting in adolescence relates to the metabolic syndrome in middle-age. Participants came from the Northern Swedish Cohort, a 27-year cohort study of school leavers (effective n = 881, 82% of the original cohort). A score of peer problems was operationalized through form teachers' assessment of each student's isolation and popularity among school peers at age 16 years, and the metabolic syndrome was measured by clinical measures at age 43 according to established criteria. Additional information on health, health behaviors, achievement and social circumstances were collected from teacher interviews, school records, clinical measurements and self-administered questionnaires. Logistic regression was used as the main statistical method. Results showed a dose-response relationship between peer problems in adolescence and metabolic syndrome in middle-age, corresponding to 36% higher odds for the metabolic syndrome at age 43 for each SD higher peer problems score at age 16. The association remained significant after adjustment for health, health behaviors, school adjustment or family circumstances in adolescence, and for psychological distress, health behaviors or social circumstances in adulthood. In analyses stratified by sex, the results were significant only in women after adjustment for covariates. Peer problems were significantly related to all individual components of the metabolic syndrome. These results suggest that unsuccessful adaption to the school peer group can have enduring consequences for metabolic health.
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| 6. |
- Gustafsson, Per E, et al.
(författare)
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Fetal and life course origins of serum lipids in mid-adulthood : results from a prospective cohort study
- 2010
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 10:1, s. 484-
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: During the past two decades, the hypothesis of fetal origins of adult disease has received considerable attention. However, critique has also been raised regarding the failure to take the explanatory role of accumulation of other exposures into consideration, despite the wealth of evidence that social circumstances during the life course impact on health in adulthood. The aim of the present prospective cohort study was to examine the contributions of birth weight and life course exposures (cumulative socioeconomic disadvantage and adversity) to dyslipidemia and serum lipids in mid-adulthood. METHODS: A cohort (effective n = 824, 77%) was prospectively examined with respect to self-reported socioeconomic status as well as stressors (e.g., financial strain, low decision latitude, separation, death or illness of a close one, unemployment) at the ages of 16, 21, 30 and 43 years; summarized in cumulative socioeconomic disadvantage and cumulative adversity. Information on birth weight was collected from birth records. Participants were assessed for serum lipids (total cholesterol, low- and high-density lipoprotein cholesterol and triglycerides), apolipoproteins (A1 and B) and height and weight (for the calculation of body mass index, BMI) at age 43. Current health behavior (alcohol consumption, smoking and snuff use) was reported at age 43. RESULTS: Cumulative life course exposures were related to several outcomes; mainly explained by cumulative socioeconomic disadvantage in the total sample (independently of current health behaviors but attenuated by current BMI) and also by cumulative adversity in women (partly explained by current health behavior but not by BMI). Birth weight was related only to triglycerides in women, independently of life course exposures, health behaviors and BMI. No significant association of either exposure was observed in men. CONCLUSIONS: Social circumstances during the life course seem to be of greater importance than birth weight for dyslipidemia and serum lipid levels in adulthood.
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| 7. |
- Gustafsson, Per E, et al.
(författare)
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Is body size at birth related to circadian salivary cortisol levels in adulthood? Results from a longitudinal cohort study.
- 2010
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 10:346
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe hypothesis of fetal origins of adult disease has during the last decades received interest as an explanation of chronic, e.g. cardiovascular, disease in adulthood stemming from fetal environmental conditions. Early programming and enduring dysregulations of the hypothalamic-pituitary-adrenal (HPA axis), with cortisol as its end product, has been proposed as a possible mechanism by which birth weight influence later health status. However, the fetal origin of the adult cortisol regulation has been insufficiently studied. The present study aims to examine if body size at birth is related to circadian cortisol levels at 43 years.MethodsParticipants were drawn from a prospective cohort study (n = 752, 74.5%). Salivary cortisol samples were collected at four times during one day at 43 years, and information on birth size was collected retrospectively from delivery records. Information on body mass during adolescence and adulthood and on health behavior, medication and medical conditions at 43 years was collected prospectively by questionnaire and examined as potential confounders. Participants born preterm or < 2500 g were excluded from the main analyses.ResultsAcross the normal spectrum, size at birth (birth weight and ponderal index) was positively related to total (area under the curve, AUC) and bedtime cortisol levels in the total sample. Results were more consistent in men than in women. Descriptively, participants born preterm or < 2500 g also seemed to display elevated evening and total cortisol levels. No associations were found for birth length or for the cortisol awakening response (CAR).ConclusionsThese results are contradictory to previously reported negative associations between birth weight and adult cortisol levels, and thus tentatively question the assumption that only low birth weight predicts future physiological dysregulations.
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| 8. |
- Gustafsson, Per E., et al.
(författare)
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Life-course accumulation of neighborhood disadvantage and allostatic load : empirical integration of three social determinants of health frameworks
- 2014
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Ingår i: American Journal of Public Health. - : American Public Health Association. - 0090-0036 .- 1541-0048. ; 104:5, s. 904-910
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: We examined if the accumulation of neighborhood disadvantages from adolescence to mid-adulthood were related to allostatic load, a measure of cumulative biological risk, in mid-adulthood, and explored whether this association was similar in women and men.METHODS: Data were from the participants in the Northern Swedish Cohort (analytical n = 818) at ages 16, 21, 30, and 43 years in 1981, 1986, 1995, and 2008. Personal living conditions were self-reported at each wave. At age 43 years, 12 biological markers were measured to operationalize allostatic load. Registered data for all residents in the cohort participants' neighborhoods at each wave were used to construct a cumulative measure of neighborhood disadvantage. Associations were examined in ordinary least-squares regression models.RESULTS: We found that cumulative neighborhood disadvantage between ages 16 and 43 years was related to higher allostatic load at age 43 years after adjusting for personal living conditions in the total sample (B = 0.11; P = .004) and in men (B = 0.16; P = .004), but not in women (B = 0.07; P = .248).CONCLUSIONS: Our findings suggested that neighborhood disadvantage acted cumulatively over the life course on biological wear and tear, and exemplified the gains of integrating social determinants of health frameworks.
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| 9. |
- Gustafsson, Per E, et al.
(författare)
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Life-course socioeconomic trajectories and diurnal cortisol regulation in adulthood
- 2010
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Ingår i: Psychoneuroendocrinology. - Oxford : Pergamon P.. - 0306-4530 .- 1873-3360. ; 35:4, s. 613-623
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Tidskriftsartikel (refereegranskat)abstract
- Although the health risk of socioeconomic disadvantage over the life-course is fairly established, the mechanisms are less studied. One candidate pathway is long-term dysregulation of cortisol. This study assesses whether socioeconomic trajectories from adolescence to adulthood influences the regulation of cortisol in mid-adulthood, and further investigates the importance of adolescence as a critical period and of accumulation of socioeconomic disadvantage. Participants were drawn from a 27-year prospective cohort study (n = 732, 68% of the original cohort). Information on socioeconomic status (SES) was collected at the ages of 16 (based on parental occupation), 21, 30 and 43 (based on own occupation) years, and at 43 years participants collected one-day salivary cortisol samples at awakening, after 15 min, before lunch and at bedtime. We found that the cortisol awakening response (CAR) differed with respect to SES trajectory; those with stable low or early low/upwardly mobile SES tended to display higher CAR than those with early high/downwardly mobile, highly mobile or stable high trajectories. Further analyses revealed that early low SES was related to higher CAR, and in women low SES was related to lower bedtime cortisol, independently of later SES and potential confounders. We found no support for a linear effect of accumulation of socioeconomic disadvantage. In conclusion, our study gives support for an independent effect of low socioeconomic status early in life, on the regulation of cortisol in adulthood.
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| 10. |
- Gustafsson, Per E., et al.
(författare)
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Residential Selection across the Life Course : Adolescent Contextual and Individual Determinants of Neighborhood Disadvantage in Mid-Adulthood
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11, s. e80241-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Numerous cross-sectional studies have examined neighborhood effects on health. Residential selection in adulthood has been stressed as an important cause of selection bias but has received little empirical attention, particularly its determinants from the earlier life course. The present study aims to examine whether neighborhood, family, school, health behaviors and health in adolescence are related to socioeconomic disadvantage of one's neighborhood of residence in adulthood. Methods: Based on the prospective Northern Swedish Cohort (analytical N = 971, 90.6% retention rate), information was collected at age 16 years concerning family circumstances, school adjustment, health behaviors and mental and physical health. Neighborhood register data was linked to the cohort and used to operationalize aggregated measures of neighborhood disadvantage (ND) at age 16 and 42. Data was analyzed with linear mixed models, with ND in adulthood regressed on adolescent predictors and neighborhood of residence in adolescence as the level-2 unit. Results: Neighborhood disadvantage in adulthood was clustered by neighborhood of residence in adolescence (ICC = 8.6%). The clustering was completely explained by ND in adolescence. Of the adolescent predictors, ND (b =.14 (95% credible interval =.07-.22)), final school marks (b =-.18 (-.26--.10)), socioeconomic disadvantage (b =.07 (.01-.14)), and, with borderline significance, school peer problems (b =-.07 (-.00-.13)), were independently related to adulthood ND in the final adjusted model. In sex-stratified analyses, the most important predictors were school marks (b =-.21 (-.32--.09)) in women, and neighborhood of residence (ICC = 15.5%) and ND (b =.20 (.09-.31)) in men. Conclusions: These findings show that factors from adolescence - which also may impact on adult health - could influence the neighborhood context in which one will live in adulthood. This indicates that residential selection bias in neighborhood effects on health research may have its sources in early life.
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