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  • 1.
    Aare, Kätlin
    et al.
    Stockholms universitet, Humanistiska fakulteten, Institutionen för lingvistik. University of Tartu, Estonia.
    Włodarczak, Marcin
    Stockholms universitet, Humanistiska fakulteten, Institutionen för lingvistik.
    Heldner, Mattias
    Stockholms universitet, Humanistiska fakulteten, Institutionen för lingvistik.
    Breath holds in spontaneous speech2019Inngår i: Eesti ja soome-ugri keeleteaduse ajakiri, ISSN 1736-8987, E-ISSN 2228-1339, Vol. 10, nr 1, s. 13-34Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This article provides a first quantitative overview of the timing and volume-related properties of breath holds in spontaneous conversations. Firstly, we investigate breath holds based on their position within the coinciding respiratory interval amplitude. Secondly, we investigate breath holds based on their timing within the respiratory intervals and in relation to communicative activity following breath holds. We hypothesise that breath holds occur in different regions of the lung capacity range and at different times during the respiratory phase, depending on the conversational and physiological activity following breath holds. The results suggest there is not only considerable variation in both the time and lung capacity scales, but detectable differences are also present in breath holding characteristics involving laughter and speech preparation, while breath holds coinciding with swallowing are difficult to separate from the rest of the data based on temporal and volume information alone.

  • 2. Aarseth, Espen
    et al.
    Edman, Johan
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för socialvetenskaplig alkohol- och drogforskning (SoRAD). Stockholms universitet, Samhällsvetenskapliga fakulteten, Sociologiska institutionen.
    Helmersson Bergmark, Karin
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Sociologiska institutionen.
    van Rooij, Antonius J.
    Scholars’ open debate paper on the World Health Organization ICD-11 Gaming Disorder proposal2017Inngår i: Journal of Behavioral Addictions, ISSN 2062-5871, E-ISSN 2063-5303, Vol. 6, nr 3, s. 267-270Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Concerns about problematic gaming behaviors deserve our full attention. However, we claim that it is far from clear that these problems can or should be attributed to a new disorder. The empirical basis for a Gaming Disorder proposal, such as in the new ICD-11, suffers from fundamental issues. Our main concerns are the low quality of the research base, the fact that the current operationalization leans too heavily on substance use and gambling criteria, and the lack of consensus on symptomatology and assessment of problematic gaming. The act of formalizing this disorder, even as a proposal, has negative medical, scientific, public-health, societal, and human rights fallout that should be considered. Of particular concern are moral panics around the harm of video gaming. They might result in premature application of diagnosis in the medical community and the treatment of abundant false-positive cases, especially for children and adolescents. Second, research will be locked into a confirmatory approach, rather than an exploration of the boundaries of normal versus pathological. Third, the healthy majority of gamers will be affected negatively. We expect that the premature inclusion of Gaming Disorder as a diagnosis in ICD-11 will cause significant stigma to the millions of children who play video games as a part of a normal, healthy life. At this point, suggesting formal diagnoses and categories is premature: the ICD-11 proposal for Gaming Disorder should be removed to avoid a waste of public health resources as well as to avoid causing harm to healthy video gamers around the world.

    Fulltekst (pdf)
    fulltext
  • 3.
    Aasa, Jenny
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi.
    Granath, Fredrik
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi.
    Cancer risk estimation of glycidol based on rodent carcinogenicity studies, a multiplicative risk model and in vivo dosimetry2019Inngår i: Food and Chemical Toxicology, ISSN 0278-6915, E-ISSN 1873-6351, Vol. 128, s. 54-60Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Here we evaluate a multiplicative (relative) risk model for improved cancer risk estimation of genotoxic compounds. According to this model, cancer risk is proportional to the background tumor incidence and to the internal dose of the genotoxic compound. Furthermore, the relative risk coefficient per internal dose is considered to be approximately the same across tumor sites, sex, and species. In the present study, we demonstrate that the relative risk model is valid for cancer risk estimation of glycidol, a common food contaminant. Published tumor data from glycidol carcinogenicity studies in mice and rats were evaluated in combination with internal dose estimates from hemoglobin adduct measurements in blood from mice and rats treated with glycidol in short-term studies. A good agreement between predicted and observed tumor incidence in responding sites was demonstrated in the animals, supporting a relative risk coefficient that is independent of tumor site, sex, and species. There was no significant difference between the risk coefficients for mice (5.1% per mMh) and rats (5.4% per mMh) when considering internal doses of glycidol. Altogether, this mechanism-based risk model gives a reliable risk coefficient, which then was extrapolated to humans considering internal dose, and background cancer incidence.

  • 4.
    Aasa, Jenny
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi.
    Vryonidis, Efstathios
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi.
    Abramsson-Zetterberg, Lilianne
    Törnqvist, Margareta
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi.
    Internal Doses of Glycidol in Children and Estimation of Associated Cancer Risk2019Inngår i: Toxics, E-ISSN 2305-6304, Vol. 7, nr 1, artikkel-id 7Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The general population is exposed to the genotoxic carcinogen glycidol via food containing refined edible oils where glycidol is present in the form of fatty acid esters. In this study, internal (in vivo) doses of glycidol were determined in a cohort of 50 children and in a reference group of 12 adults (non-smokers and smokers). The lifetime in vivo doses and intakes of glycidol were calculated from the levels of the hemoglobin (Hb) adduct N-(2,3-dihydroxypropyl)valine in blood samples from the subjects, demonstrating a fivefold variation between the children. The estimated mean intake (1.4 mu g/kg/day) was about two times higher, compared to the estimated intake for children by the European Food Safety Authority. The data from adults indicate that the non-smoking and smoking subjects are exposed to about the same or higher levels compared to the children, respectively. The estimated lifetime cancer risk (200/10(5)) was calculated by a multiplicative risk model from the lifetime in vivo doses of glycidol in the children, and exceeds what is considered to be an acceptable cancer risk. The results emphasize the importance to further clarify exposure to glycidol and other possible precursors that could give a contribution to the observed adduct levels.

  • 5. Aayesh,
    et al.
    Bilal Qureshi, Muhammad
    Afzaal, Muhammad
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Shuaib Qureshi, Muhammad
    Gwak, Jeonghwan
    Fuzzy-Based Automatic Epileptic Seizure Detection Framework2022Inngår i: Computers, Materials and Continua, ISSN 1546-2218, E-ISSN 1546-2226, Vol. 70, nr 3, s. 5601-5630Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Detection of epileptic seizures on the basis of Electroencephalogram (EEG) recordings is a challenging task due to the complex, non-stationary and non-linear nature of these biomedical signals. In the existing literature, a number of automatic epileptic seizure detection methods have been proposed that extract useful features from EEG segments and classify them using machine learning algorithms. Some characterizing features of epileptic and non-epileptic EEG signals overlap; therefore, it requires that analysis of signals must be performed from diverse perspectives. Few studies analyzed these signals in diverse domains to identify distinguishing characteristics of epileptic EEG signals. To pose the challenge mentioned above, in this paper, a fuzzy-based epileptic seizure detection model is proposed that incorporates a novel feature extraction and selection method along with fuzzy classifiers. The proposed work extracts pattern features along with time-domain, frequency domain, and non-linear analysis of signals. It applies a feature selection strategy on extracted features to get more discriminating features that build fuzzy machine learning classifiers for the detection of epileptic seizures. The empirical evaluation of the proposed model was conducted on the benchmark Bonn EEG dataset. It shows significant accuracy of 98% to 100% for normal vs. ictal classification cases while for three class classification of normal vs. inter-ictal vs. ictal accuracy reaches to above 97.5%. The obtained results for ten classification cases (including normal, seizure or ictal, and seizure-free or inter-ictal classes) prove the superior performance of proposed work as compared to other state-of-the-art counterparts.

  • 6.
    Abbasi, Alireza
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för fysikalisk kemi, oorganisk kemi och strukturkemi.
    Lindqvist-Reis, Patric
    Eriksson, Lars
    Sandström, Dick
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för fysikalisk kemi, oorganisk kemi och strukturkemi.
    Lidin, Sven
    Persson, Ingmar
    Sandström, Magnus
    Highly hydrated cations: Deficiency, mobility and coordination of water in crystalline nonahydrated scandium(III), yttrium(III) and lanthanoid(III) trifluoromethanesulfonate2005Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 11, nr 14, s. 4065-4077Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Trivalent lanthanide-like metal ions coordinate nine water oxygen atoms, which form a tricapped trigonal prism in a large number of crystalline hydrates. Water deficiency, randomly distributed over the capping positions, was found for the smallest metal ions in the isomorphous nonahydrated trifluoromethanesulfonates, [M(H2O)(n)]CF3SO3)(3), in which M=Sc-III, Lu-III, Yb-III, Tm-III or Er-III. The hydration number n increases (n=8.0(1), 8.4(1), 8.7(1), 8.8(1) and 8.96(5), respectively) with increasing ionic size. Deuterium (H-2) solid-state NMR spectroscopy revealed fast positional exchange between the coordinated capping and prism water molecules; this exchange started at temperatures higher than about 280 K for lutetium(m) and below 268 K for scandium(m). Similar positional exchange for the fully nonahydrated yttrium(m) and lanthanum(m) compounds started at higher temperatures, over about 330 and 360 K, respectively. An exchange mechanism is proposed that can exchange equatorial and capping water molecules within the restrictions of the crystal lattice, even for fully hydrated lanthanoid(III) ions. Phase transitions occurred for all the water-deficient compounds at; 185 K. The hydrated scandium(III) trifluoromethanesulfonate transforms reversibly (Delta H degrees= -0.80(1) kJ mol(-1) on cooling) to a trigonal unit cell that is almost nine times larger, with the scandium ion surrounded by seven fully occupied and two partly occupied oxygen atom positions in a distorted capped trigonal prism. The hydrogen bonding to the trifluoromethanesulfonate anions stabilises the trigonal prism of water ligands, even for the crowded hydration sphere of the smallest metal ions in the series. Implications for the Lewis acid catalytic activity of the hydrated scandium(III) and lanthanoid(III) trifluoromethanesulfonates for organic syntheses performed in aqueous media are discussed.

  • 7. Abbo, Catherine
    et al.
    Ekblad, Solvig
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet.
    Waako, Paul
    Okello, Elialilia
    Muhwezi, Wilson
    Musisi, Seggane
    Psychological distress and associated factors among the attendees of traditional healing practices in Jinja and Iganga districts, Eastern Uganda: a cross-sectional study.2008Inngår i: International Journal of Mental Health Systems, E-ISSN 1752-4458, Vol. 2, nr 1, s. 16-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Psychological distress and associated factors among the attendees of traditional healing practices in Jinja and Iganga districts, Eastern Uganda: a cross-sectional study.

    Abbo C, Ekblad S, Waako P, Okello E, Muhwezi W, Musisi S.

    Karolinska Institutet, Department of Clinical Neuroscience, Section of Psychiatry, Stockholm, Sweden. cathya180@gmail.com.

    ABSTRACT: BACKGROUND: Mental health problems are a major public health concern worldwide. Evidence shows that African communities, including Uganda, use both modern and traditional healing systems. There is limited literature about the magnitude of psychological distress and associated factors among attendees of traditional healing practices. This study aimed to determine the prevalence and associated factors of psychological distress among attendees of traditional healing practices in two districts in Uganda. METHODS: Face-to-face interviews with the Lusoga version of the Self Reporting Questionnaire (SRQ-20) were carried out with 400 patients over the age of 18 years attending traditional healing in Iganga and Jinja districts in Eastern Uganda. Patients were recruited consecutively in all the traditional healers' shrines that could be visited in the area. Persons with 6 or more positive responses to the SRQ were identified as having psychological distress. Prevalence was estimated and odds ratios of having psychological distress were obtained with multiple logistic regression analysis. RESULTS: 387 questionnaire responses were analyzed. The prevalence of psychological distress in connection with attendance at the traditional healers' shrines was 65.1%. Having a co-wife and having more than four children were significantly associated with psyclogical distress. Among the socioeconomic indicators, lack of food and having debts were significantly associated with psychological distress. The distressed group was more likely to need explanations for ill health. Those who visited both the healer and a health unit were less likely to be distressed. CONCLUSION: This study provides evidence that a substantial proportion of attendees of traditional healing practices suffer from psychological distress. Associated factors include poverty, number of children, polygamy, reason for visiting the healer and use of both traditional healing and biomedical health units. These findings may be useful for policy makers and biomedical health workers for the engagement with traditional healers.

  • 8. Abd El-Wahed, Aida A.
    et al.
    Khalifa, Shaden A. M.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Elashal, Mohamed H.
    Musharraf, Syed G.
    Saeed, Aamer
    Khatib, Alfi
    Tahir, Haroon Elrasheid
    Zou, Xiaobo
    Al Naggar, Yahya
    Mehmood, Arshad
    Wang, Kai
    El-Seedi, Hesham R.
    Cosmetic Applications of Bee Venom2021Inngår i: Toxins, ISSN 2072-6651, E-ISSN 2072-6651, Vol. 13, nr 11, artikkel-id 810Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Bee venom (BV) is a typical toxin secreted by stingers of honeybee workers. BV and BV therapy have long been attractive to different cultures, with extensive studies during recent decades. Nowadays, BV is applied to combat several skin diseases, such as atopic dermatitis, acne vulgaris, alopecia, vitiligo, and psoriasis. BV is used extensively in topical preparations as cosmetics and used as dressing for wound healing, as well as in facemasks. Nevertheless, the safety of BV as a therapeutic choice has always been a concern due to the immune system reaction in some people due to BV use. The documented unfavorable impact is explained by the fact that the skin reactions to BV might expand to excessive immunological responses, including anaphylaxis, that typically resolve over numerous days. This review aims to address bee venom therapeutic uses in skin cosmetics.

  • 9. Abdallah, Qasem M. A.
    et al.
    Phillips, Roger M.
    Johansson, Fredrik
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Helleday, Thomas
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för genetik, mikrobiologi och toxikologi.
    Cosentino, Laura
    Abdel-Rahman, Hamdy
    Etzad, Jasarat
    Wheelhouse, Richard T.
    Kiakos, Konstantinos
    Bingham, John P.
    Hartley, John A.
    Patterson, Laurence H.
    Pors, Klaus
    Minor structural modifications to alchemix influence mechanism of action and pharmacological activity2012Inngår i: Biochemical Pharmacology, ISSN 0006-2952, E-ISSN 1356-1839, Vol. 83, nr 11, s. 1514-1522Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Alchemix is an exemplar of a class of anthraquinone with efficacy against multidrug resistant tumours. We have explored further the mechanism of action of alchemix and investigated the effect of extending its side arm bearing the alkylating functionality with regard to DNA binding and activity against multidrug resistant cancer cells. Increasing the distance between the intercalating chromophore and the alkylating functionality of ICT2901 (propyl), ICT2902 (butyl) and ICT2903 (pentyl), led to a higher number of DNA alkylation sites, more potent topoisomerase II inhibition and generated more apoptotic and necrotic cells when analysed in p53-proficient HCT116 cells. Intriguingly, alchemix, the compound with the shortest distance between its intercalative chromophore and alkylating functionality (ethyl), did not conform to this SAR. A different toxicity pattern against DNA repair defective CHO cell lines as well as arrest of cells in Cl supports a somewhat distinct mode of action by alchemix compared with its analogues. Importantly, both alchemix and ICT2901 demonstrated greater cytotoxic activity against anthraquinone-resistant MCF-7/adr cells than wild-type MCF-7 cells. Subtle synthetic modification in this anthraquinone series has led to significant changes to the stability of DNA-compound complexes and cellular activity. Given that the failure of chemotherapy in the clinic is often associated with MDR, the results of both alchemix and ICT2901 represent important advances towards improved therapies.

  • 10.
    Abdel Rehim, Abbi
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för analytisk kemi.
    Abdel Rehim, Mohamed
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för analytisk kemi.
    Screening and determination of drugs in human saliva utilizing microextraction by packed sorbent and liquid chromatography-tandem mass spectrometry2013Inngår i: BMC Biomedical chromotography, ISSN 0269-3879, E-ISSN 1099-0801, Vol. 27, nr 9, s. 1188-1191Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study presents a new method for collecting and handling saliva samples using an automated analytical microsyringe and microextraction by packed syringe (MEPS). The screening and determination of lidocaine in human saliva samples utilizing MEPS and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were carried out. An exact volume of saliva could be collected. The MEPS C-8-cartridge could be used for 50 extractions before it was discarded. The extraction recovery was about 60%. The pharmacokinetic curve of lidocaine in saliva using MEPS-LC-MS/MS is reported.

  • 11. Abdelnour, Carla
    et al.
    Ferreira, Daniel
    van de Beek, Marleen
    Cedres, Nira
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Perception och psykofysik. Karolinska Institutet, Sweden.
    Oppedal, Ketil
    Cavallin, Lena
    Blanc, Frédéric
    Bousiges, Olivier
    Wahlund, Lars-Olof
    Pilotto, Andrea
    Padovani, Alessandro
    Boada, Mercè
    Pagonabarraga, Javier
    Kulisevsky, Jaime
    Aarsland, Dag
    Lemstra, Afina W.
    Westman, Eric
    Parsing heterogeneity within dementia with Lewy bodies using clustering of biological, clinical, and demographic data2022Inngår i: Alzheimer's Research & Therapy, E-ISSN 1758-9193, Vol. 14, nr 1, artikkel-id 14Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Dementia with Lewy bodies (DLB) includes various core clinical features that result in different phenotypes. In addition, Alzheimer's disease (AD) and cerebrovascular pathologies are common in DLB. All this increases the heterogeneity within DLB and hampers clinical diagnosis. We addressed this heterogeneity by investigating subgroups of patients with similar biological, clinical, and demographic features.

    Methods: We studied 107 extensively phenotyped DLB patients from the European DLB consortium. Factorial analysis of mixed data (FAMD) was used to identify dimensions in the data, based on sex, age, years of education, disease duration, Mini-Mental State Examination (MMSE), cerebrospinal fluid (CSF) levels of AD biomarkers, core features of DLB, and regional brain atrophy. Subsequently, hierarchical clustering analysis was used to subgroup individuals based on the FAMD dimensions.

    Results: We identified 3 dimensions using FAMD that explained 38% of the variance. Subsequent hierarchical clustering identified 4 clusters. Cluster 1 was characterized by amyloid-beta and cerebrovascular pathologies, medial temporal atrophy, and cognitive fluctuations. Cluster 2 had posterior atrophy and showed the lowest frequency of visual hallucinations and cognitive fluctuations and the worst cognitive performance. Cluster 3 had the highest frequency of tau pathology, showed posterior atrophy, and had a low frequency of parkinsonism. Cluster 4 had virtually normal AD biomarkers, the least regional brain atrophy and cerebrovascular pathology, and the highest MMSE scores.

    Conclusions: This study demonstrates that there are subgroups of DLB patients with different biological, clinical, and demographic characteristics. These findings may have implications in the diagnosis and prognosis of DLB, as well as in the treatment response in clinical trials.

  • 12. Abdollahi, Abbas
    et al.
    Abu Talib, Mansor
    Carlbring, Per
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Klinisk psykologi.
    Harvey, Richard
    Yaacob, Siti Nor
    Ismail, Zanariah
    Problem-solving skills and perceived stress among undergraduate students: The moderating role of hardiness2018Inngår i: Journal of Health Psychology, ISSN 1359-1053, E-ISSN 1461-7277, Vol. 23, nr 10, s. 1321-1331Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study was designed to examine the relationships between problem-solving skills, hardiness, and perceived stress and to test the moderating role of hardiness in the relationship between problem-solving skills and perceived stress among 500 undergraduates from Malaysian public universities. The analyses showed that undergraduates with poor problem-solving confidence, external personal control of emotion, and approach-avoidance style were more likely to report perceived stress. Hardiness moderated the relationships between problem-solving skills and perceived stress. These findings reinforce the importance of moderating role of hardiness as an influencing factor that explains how problem-solving skills affect perceived stress among undergraduates.

  • 13. Abdollahi, Abbas
    et al.
    Carlbring, Per
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Klinisk psykologi.
    Coping Style as a Moderator of Perfectionism and Suicidal Ideation Among Undergraduate Students2017Inngår i: Journal of Rational-Emotive & Cognitive-Behavior Therapy, ISSN 0894-9085, E-ISSN 1573-6563, Vol. 35, nr 3, s. 223-239Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Suicide is a serious and growing public health problem and remains an unnecessary cause of death globally. In Iran, the highest prevalence of acute and chronic suicidal ideation is among young people aged 16-24. This study investigates the relationship between coping style, two types of perfectionism, and suicidal ideation among undergraduates, and examines coping style as a moderator of the relationship between perfectionism and suicidal ideation. Multi-stage cluster random sampling was employed to recruit 547 undergraduate students aged 19-24 years from the Islamic Azad University of Karaj. Structural Equation Modelling indicated that suicidal ideation was negatively associated with adaptive perfectionism and task-focused coping but positively associated with emotion-focused coping, avoidance coping, and maladaptive perfectionism. Coping style (including the three styles of task-focused, emotion-focused, and avoidance coping) was found to moderate the relationship between perfectionism and suicidal ideation. The study advances understanding of the importance of coping style in this context and explains how perfectionism affects suicidal ideation.

  • 14. Abelein, Axel
    et al.
    Ciofi-Baffoni, Simone
    Mörman, Cecilia
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik. Karolinska Institutet, Sweden.
    Kumar, Rakesh
    Giachetti, Andrea
    Piccioli, Mario
    Biverstål, Henrik
    Molecular Structure of Cu(II)-Bound Amyloid-β Monomer Implicated in Inhibition of Peptide Self-Assembly in Alzheimer’s Disease2022Inngår i: JACS Au, E-ISSN 2691-3704, Vol. 2, nr 11, s. 2571-2584Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Metal ions, such as copper and zinc ions, have been shown to strongly modulate the self-assembly of the amyloid-β (Aβ) peptide into insoluble fibrils, and elevated concentrations of metal ions have been found in amyloid plaques of Alzheimer’s patients. Among the physiological transition metal ions, Cu(II) ions play an outstanding role since they can trigger production of neurotoxic reactive oxygen species. In contrast, structural insights into Cu(II) coordination of Aβ have been challenging due to the paramagnetic nature of Cu(II). Here, we employed specifically tailored paramagnetic NMR experiments to determine NMR structures of Cu(II) bound to monomeric Aβ. We found that monomeric Aβ binds Cu(II) in the N-terminus and combined with molecular dynamics simulations, we could identify two prevalent coordination modes of Cu(II). For these, we report here the NMR structures of the Cu(II)–bound Aβ complex, exhibiting heavy backbone RMSD values of 1.9 and 2.1 Å, respectively. Further, applying aggregation kinetics assays, we identified the specific effect of Cu(II) binding on the Aβ nucleation process. Our results show that Cu(II) efficiently retards Aβ fibrillization by predominately reducing the rate of fibril-end elongation at substoichiometric ratios. A detailed kinetic analysis suggests that this specific effect results in enhanced Aβ oligomer generation promoted by Cu(II). These results can quantitatively be understood by Cu(II) interaction with the Aβ monomer, forming an aggregation inert complex. In fact, this mechanism is strikingly similar to other transition metal ions, suggesting a common mechanism of action of retarding Aβ self-assembly, where the metal ion binding to monomeric Aβ is a key determinant. 

  • 15.
    Abelein, Axel
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Gräslund, Astrid
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Danielsson, Jens
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Zinc as chaperone-mimicking agent for retardation of amyloid beta peptide fibril formation2015Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, nr 17, s. 5407-5412Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Metal ions have emerged to play a key role in the aggregation process of amyloid beta (A beta) peptide that is closely related to the pathogenesis of Alzheimer's disease. A detailed understanding of the underlying mechanistic process of peptide-metal interactions, however, has been challenging to obtain. By applying a combination of NMR relaxation dispersion and fluorescence kinetics methods we have investigated quantitatively the thermodynamic A beta-Zn2+ binding features as well as how Zn2+ modulates the nucleation mechanism of the aggregation process. Our results show that, under near-physiological conditions, substoichiometric amounts of Zn2+ effectively retard the generation of amyloid fibrils. A global kinetic profile analysis reveals that in the absence of zinc A beta(40) aggregation is driven by a monomer-dependent secondary nucleation process in addition to fibril-end elongation. In the presence of Zn2+, the elongation rate is reduced, resulting in reduction of the aggregation rate, but not a complete inhibition of amyloid formation. We show that Zn2+ transiently binds to residues in the N terminus of the monomeric peptide. A thermodynamic analysis supports a model where the N terminus is folded around the Zn2+ ion, forming a marginally stable, short-lived folded A beta(40) species. This conformation is highly dynamic and only a few percent of the peptide molecules adopt this structure at any given time point. Our findings suggest that the folded A beta(40)-Zn2+ complex modulates the fibril ends, where elongation takes place, which efficiently retards fibril formation. In this conceptual framework we propose that zinc adopts the role of a minimal antiaggregation chaperone for A beta(40).

  • 16. Abend, M.
    et al.
    Amundson, S. A.
    Badie, C.
    Brzoska, K.
    Hargitai, R.
    Kriehuber, R.
    Schüle, S.
    Kis, E.
    Ghandhi, S. A.
    Lumniczky, K.
    Morton, S. R.
    O'Brien, G.
    Oskamp, D.
    Ostheim, P.
    Siebenwirth, C.
    Shuryak, I.
    Szatmári, T.
    Unverricht-Yeboah, M.
    Ainsbury, E.
    Bassinet, C.
    Kulka, U.
    Oestreicher, U.
    Ristic, Y.
    Trompier, F.
    Wójcik, Andrzej
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Waldner, L.
    Port, M.
    Inter-laboratory comparison of gene expression biodosimetry for protracted radiation exposures as part of the RENEB and EURADOS WG10 2019 exercise2021Inngår i: Scientific Reports, E-ISSN 2045-2322, Vol. 11, nr 1, artikkel-id 9756Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Large-scale radiation emergency scenarios involving protracted low dose rate radiation exposure (e.g. a hidden radioactive source in a train) necessitate the development of high throughput methods for providing rapid individual dose estimates. During the RENEB (Running the European Network of Biodosimetry) 2019 exercise, four EDTA-blood samples were exposed to an Iridium-192 source (1.36 TBq, Tech-Ops 880 Sentinal) at varying distances and geometries. This resulted in protracted doses ranging between 0.2 and 2.4 Gy using dose rates of 1.5-40 mGy/min and exposure times of 1 or 2.5 h. Blood samples were exposed in thermo bottles that maintained temperatures between 39 and 27.7 degrees C. After exposure, EDTA-blood samples were transferred into PAXGene tubes to preserve RNA. RNA was isolated in one laboratory and aliquots of four blinded RNA were sent to another five teams for dose estimation based on gene expression changes. Using an X-ray machine, samples for two calibration curves (first: constant dose rate of 8.3 mGy/min and 0.5-8 h varying exposure times; second: varying dose rates of 0.5-8.3 mGy/min and 4 h exposure time) were generated for distribution. Assays were run in each laboratory according to locally established protocols using either a microarray platform (one team) or quantitative real-time PCR (qRT-PCR, five teams). The qRT-PCR measurements were highly reproducible with coefficient of variation below 15% in >= 75% of measurements resulting in reported dose estimates ranging between 0 and 0.5 Gy in all samples and in all laboratories. Up to twofold reductions in RNA copy numbers per degree Celsius relative to 37 degrees C were observed. However, when irradiating independent samples equivalent to the blinded samples but increasing the combined exposure and incubation time to 4 h at 37 degrees C, expected gene expression changes corresponding to the absorbed doses were observed. Clearly, time and an optimal temperature of 37 degrees C must be allowed for the biological response to manifest as gene expression changes prior to running the gene expression assay. In conclusion, dose reconstructions based on gene expression measurements are highly reproducible across different techniques, protocols and laboratories. Even a radiation dose of 0.25 Gy protracted over 4 h (1 mGy/min) can be identified. These results demonstrate the importance of the incubation conditions and time span between radiation exposure and measurements of gene expression changes when using this method in a field exercise or real emergency situation.

  • 17. Aboagye, Emmanuel
    et al.
    Gustafsson, Klas
    Jensen, Irene
    Hagberg, Jan
    Aronsson, Gunnar
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Arbets- och organisationspsykologi.
    Marklund, Staffan
    Leineweber, Constanze
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet.
    Bergström, Gunnar
    What is Number of Days in Number of Times?: Associations Between, and Responsiveness of, Two Sickness Presenteeism Measures2020Inngår i: Journal of Occupational and Environmental Medicine, ISSN 1076-2752, E-ISSN 1536-5948, Vol. 62, nr 5, s. e180-e185Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To examine the associations between sickness presenteeism (SP) reported as number of days with SP reported as number of times and to evaluate their responsiveness.

    Methods: The study population (n = 454) consisted of employed individuals, at risk of long-term sickness absence. Correlation analyses were performed to examine associations between the two SP measures and external constructs such as work performance, general health, and registered sick leave. Both SP constructs were measured several times to examine responsiveness.

    Results: The SP measures are moderately correlated. They moderately correlated with work performance and health status measures. SP reported as number of times seems to be more sensitive than number of days in detecting changes after rehabilitation.

    Conclusions: Numerical or categorical constructs are valid sources of data on SP. However, categorized SP seems to be more responsive.

  • 18.
    Abougazar, Eman Silmy
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för folkhälsovetenskap.
      Barriers to equal access to eHealth in Stockholm  : A qualitative study2022Independent thesis Advanced level (degree of Master (Two Years)), 80 poäng / 120 hpOppgave
    Abstract [en]

    The aim behind this study was to observe and understand barriers to access the eHealth system equally. The study was conducted in Stockholm based on qualitative data in which semi- structured interviews were conducted among 15 interviewees from different localities of Stockholm. The findings from the collected data revealed that language barriers, lack of knowledge about digital literacy, unawareness of Swedish healthcare services, psychological and social barriers, safety and privacy concerns, and the lack of an e-identification are all major barriers to accessing the eHealth system. From the data, it has also been observed that the main causes of the aforementioned hurdles are based on varied socioeconomic levels, literacy conditions of an individual, cultural background, and age. Another important observation shows that highly qualified people with limited language abilities have a difficult time using eHealth services. 

    Keywords 

    Ehealth, Covid-19, nudge approach, digital literacy, linguistic skills, Bank ID, 1177.se, Alltid öppet. 

    Fulltekst (pdf)
    fulltext
  • 19.
    Abougazar, Eman Silmy
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för folkhälsovetenskap.
    Barriers to equal access to eHealth in Stockholm: A qualitative study2022Independent thesis Advanced level (degree of Master (Two Years)), 20 poäng / 30 hpOppgave
    Abstract [en]

    The aim behind this study was to observe and understand barriers to access the eHealth system equally. The study was conducted in Stockholm based on qualitative data in which semi- structured interviews were conducted among 15 interviewees from different localities of Stockholm. The findings from the collected data revealed that language barriers, lack of knowledge about digital literacy, unawareness of Swedish healthcare services, psychological and social barriers, safety and privacy concerns, and the lack of an e-identification are all major barriers to accessing the eHealth system. From the data, it has also been observed that the main causes of the aforementioned hurdles are based on varied socioeconomic levels, literacy conditions of an individual, cultural background, and age. Another important observation shows that highly qualified people with limited language abilities have a difficult time using eHealth services. 

    Fulltekst (pdf)
    fulltext
  • 20. Abrahamsen, Annbjørg Selma
    et al.
    Johannesen, Ása
    Debes, Fróði
    van Leeuwen, Wessel M. A.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Stressforskningsinstitutet. Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Biologisk psykologi.
    Weihe, Pál
    Working environment and fatigue among fishers in the north Atlantic: a field study2023Inngår i: International Maritime Health, ISSN 1641-9251, E-ISSN 2081-3252, Vol. 74, nr 1, s. 1-14Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: This study investigates how Faroese deep-sea fishers’ exposure to work-related stressors affects their sleep, sleepiness, and levels of fatigue. Being constantly exposed to the unpredictable and harsh North Atlantic Ocean, having long work hours and split sleep for up to 40 days consecutively, they will arguably suffer from fatigue.

    Materials and methods: One hundred and fifty seven fishers participated in this study, and data was gathered throughout 202 days at sea. Subjective data was collected at the start and end of trips via questionnaires, sleep and sleepiness diaries and supplemented by objective sleep data through actigraphs. Ship movements were logged with a gyroscope connected to a laptop. A noise metre measured each work station and resting area, and noise exposure profiles were calculated based on each participant’s activity and location. Linear mixed-effect models investigated the effects of work exposure variables on sleep efficiency, and cumulative link mixed models measured effects on the Karolinska Sleepiness Scale and physical fatigue scale.

    Results: Time of day followed by ship movement were the exposure variables with the highest impact on the outcome variables of sleep efficiency, sleepiness and physical fatigue. The number of days at sea revealed correlations to outcome variables either by itself or interacting with the sleep periods per day. Crew size, shift system or noise did not impact outcome variables when in the model with other variables. Larger catches improved sleep efficiency but did not affect sleepiness and physical fatigue ratings.

    Conclusions: The findings indicate a chronically fatigued fisher population, and recommends urgent attention being paid to improving the structure of vessels and installing stabilators for greater stability at sea; work schedules being evaluated for protection of health; and work environments being designed that fulfill human physiological requirements in order to ensure the wellbeing and safety of those at sea.

  • 21. Abrahamsen, Annbjørg Selma
    et al.
    Weihe, Pál
    van Leeuwen, Wessel M. A.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Stressforskningsinstitutet.
    Debes, Fróði
    Impact of work exposure on cognitive performance in Faroese deep-sea fishers: a field study2022Inngår i: International Maritime Health, ISSN 1641-9251, E-ISSN 2081-3252, Vol. 73, nr 3, s. 150-161Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: This study examines the impact of work-related exposure on the cognitive performance of Faroese deep-sea fishers. Faroese fishing crews work long hours in demanding and noisy environments amidst highly uncertain and challenging weather conditions. These factors, together with compromised patterns of rest and sleep, are known to increase fatigue. Our aim was to study if changes could be measured in fishers’ cognitive performance at the end of the trip when compared with the baseline measure at the beginning.

    Materials and methods: Data was collected over 15 months (May 2017 to July 2018) from 157 fishers on 18 fishing trips which involved 202 investigative days on board. Questionnaires and six computerised cognitive tests: Simple Reaction Time, Numeric Working Memory, Corsi Blocks, Rapid Visual Information Processing, Digit Vigilance, and Card Sorting Test were used for data collection at the beginning and end of the trip. Differences between the outcomes on the two test points were analysed with one-way ANOVA comparing the performances at the beginning and end of the voyage, and two-way ANOVA to examine the interactive effect of chronotype and test occasions on the outcomes. Mixed models were used to test for the effects of predictor variables.

    Results: Significant declines in cognitive performance were observed from the beginning to the end of the trip, with decreases in visuospatial memory and reaction times, and increases in cognitive lapses. Furthermore, slowing in response times was observed in the second half of the Digit Vigilance test when comparing the halves.

    Conclusions: Declines in performance were observed from the start to the end of the trip. Furthermore, fishers performed significantly worse in the second half of some parted tests, and evening types seem less influenced by irregular work hours. These findings call for improving the safety of the vessels and their crew.

  • 22. Abrahamsen, Annbjørg
    et al.
    Weihe, Pál
    Debes, Fróði
    van Leeuwen, Wessel MA.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Stressforskningsinstitutet.
    Sleep, Sleepiness, and Fatigue on Board Faroese Fishing Vessels2022Inngår i: Nature and Science of Sleep, ISSN 1179-1608, Vol. 14, s. 347-362Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: Faroese fishers have four times more accidents than workers on land. The aim was to understand fishers’ fatigue better and how their work and sleep patterns influenced their sleepiness levels and cognitive performance.

    Materials and Methods: A total of 157 Faroese fishers wore wrist-worn actigraphs at sea and one week on land and filled in sleep and sleepiness diaries during the trip. Furthermore, a 3-minute simple reaction time (SRT) test was completed at the beginning and end of the trip. The ship’s movement and noise were also logged. The actiwatch results were analysed with mixed methods repeated measures. The sleepiness registrations and performance on the SRT-test were analysed with paired t-test. The ship movements (Pitch and roll) were divided into approximately three same-sized groups (lowest 1/3, medium 1/3, and highest 1/3) and compared against the Karolinska Sleepiness Scores (KSS ranging from 1– 9) ≥ 7 and physical tiredness (ranging from 1– 9) scores ≥ 7. Chi-square tests were used to determine the significance of these differences. Mean sleepiness scores at sea, and the proportion of sleepiness scores ≥ 7 were calculated, as well as sleepiness scores as a function of the time of day.

    Results: While at sea, fishers had more split sleep, slept less, and had lower sleep efficiency than onshore. Sleepiness was higher at the end of the trip, and cognitive decline was found. The number of major lapses was higher at the end of the trip, but with no significant difference between the median reaction times.

    Conclusion: The crew on-board the freezer longliner, who worked 8– 8 shifts, slept the most, had the longest continuous sleep periods, the highest sleep efficiency, the lowest sleepiness levels, and the highest noise exposure during their time off.

  • 23.
    Abrahamson, Maria
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för socialvetenskaplig alkohol- och drogforskning (SoRAD).
    Moral norms in older Swedish women’s drinking narratives. Enduring patterns and successively new features2012Inngår i: Nordic Studies on Alcohol and Drugs, ISSN 1455-0725, Vol. 29, nr 4, s. 371-396Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIMS - To examine how the changes in women's relationship to alcohol during the 1960s appear in narratives of situated drinking occasions. DATA - Newly collected autobiographies written by women born between 1918 and 1951 are analysed using theories by William Labov on narrative construction and Kenneth Burke on the rhetoric of motives. RESULTS - The historically restrictive attitude to women at all drinking is present in the oldest women's narratives, while the liberalisation of attitudes to alcohol that took place in the 1960s likewise marks the narratives told by the younger women, even though they when writing are of pension able age. With the writers' diminishing age, the norms framing the narratives have changed, from sobriety among the oldest women to controlled moderation among the younger. And yet, the narratives also demonstrate a stable pattern of questioning women's drinking, although the focus has shifted from tasting alcohol at all to the state of becoming intoxicated. CONCLUSIONS - A controlling norm remains in place, which the women have internalised and made their own. The mitigating circumstances and the neutralising explanations that are presented throughout indicate that the women are conscious of the narratives' deviation from the prevailing norm, and show that women take a risk in drinking alcohol. When a woman drinks she risks her femininity.

  • 24.
    Abrahamson, Maria
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för socialvetenskaplig alkohol- och drogforskning (SoRAD).
    Heimdahl, Karin
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för socialvetenskaplig alkohol- och drogforskning (SoRAD).
    Kvinnor dricker för att de mår dåligt - män dricker för att de är män: om könad diskurs i alkoholpolitiska propositioner och utredningar 1965 - 20112012Inngår i: Samhället, alkoholen och drogerna: politik, konstruktioner och dilemman / [ed] Jessica Storbjörk, Stockholm: Stockholms universitets förlag, 2012, s. 104-129Kapittel i bok, del av antologi (Annet vitenskapelig)
  • 25.
    Abrahamson, Maria
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för socialvetenskaplig alkohol- och drogforskning (SoRAD).
    Tryggvesson, Kalle
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för socialvetenskaplig alkohol- och drogforskning (SoRAD).
    Socialtjänstens användning av standardiserade klientbedömningsinstrument – ASI som retorik och praktik i två svenska kommuner2009Inngår i: Nordic Studies on Alcohol and Drugs, ISSN 1455-0725, E-ISSN 1458-6126, Vol. 26, nr 1, s. 21-39Artikkel i tidsskrift (Fagfellevurdert)
    Fulltekst (pdf)
    FULLTEXT01
  • 26.
    Abrahamsson, Klara
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om ojämlikhet i hälsa (CHESS).
    Perceived neighbourhood insecurity and psychosomatic health complaints among adolescents in Stockholm: Exploring district-level and gendered inequalities2016Independent thesis Advanced level (degree of Master (Two Years)), 20 poäng / 30 hpOppgave
    Abstract [en]

    The neighbourhood is an essential arena for adolescents’ health development and research suggests that perceived neighbourhood insecurity (PNI) is associated with socio-economic status and self-rated health. The present study explored the distribution of adolescents’ PNI and its association with psychosomatic health complaints across districts. It also examined gender differences and whether family socio-economic position, foreign background and previous exposure to crime could explain part of the association. Data came from classroom-surveys within Stockholm municipality’s 14 districts in 2010, 2012 and 2014 (n=10,291). Linear and logistic multilevel regression models were applied. Results showed that the average level of PNI varied considerably between districts and were strongly connected to its socio-demographic composition. However, individual characteristics in terms of family background and previous exposure to crime only explained a minor part of the variation in PNI across districts. Girls reported more insecurity than boys in all districts. Gender differences in PNI decreased in absolute numbers, but increased in relative numbers, as the overall ‘neighbourhood safety’ increased. Between-district differences in health were minor, but PNI was still a strong predictor of individual-level health, especially for boys. Furthermore, the predictive power of PNI on health was stronger in districts perceived as safer.

    Fulltekst (pdf)
    Abrahamsson (2016)
  • 27.
    Abramsson, Marianne
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Kulturgeografiska institutionen.
    Hagberg, Jan-Erik
    Housing plans of the oldest: ageing in semi-rural areas in Sweden2020Inngår i: Journal of Housing and the Built Environment, ISSN 1566-4910, E-ISSN 1573-7772, Vol. 35, nr 1, s. 27-43Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A number of smaller municipalities have decreasing population rates. Generally, the young move out, increasing the proportion of older people. To increase our understanding of the living conditions of an ageing population in small municipalities, a postal survey was conducted in three small, semi-rural municipalities in southern Sweden. In the survey the respondents answered questions about their living situation and their housing plans. The aim of this study was to investigate the housing situation and housing plans of the very old in semi-rural areas and research questions analysed for this study concerned the current housing situation and plans for future housing. A total of 1386 surveys were sent out in March 2014, to all inhabitants aged 80 years or more, residing in the ordinary housing market in the three municipalities, the response rate was 60%. The results show that most of the respondents were firmly rooted in the area as most of them had lived in the municipality for more than 20 years and 60% had lived in their current dwelling for more than 20 years. Ageing in place was the dominating plan, although one quarter of the respondents answered that they did not know what would happen in the future. Those who planned to move wanted to move to housing that required less maintenance and to a more central location. Residential mobility is at play also in old age as 27% of the respondents had moved at some point during the last 10 years, i.e., after the age of 70.

  • 28.
    Abramsson-Zetterberg, Lilianne
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för miljövetenskap och analytisk kemi.
    Strongly heated carbohydrate-rich food is an overlooked problem in cancer risk evaluation2018Inngår i: Food and Chemical Toxicology, ISSN 0278-6915, E-ISSN 1873-6351, Vol. 121, s. 151-155Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A cascade of compounds is produced when foodstuffs are heated at high temperatures but only a few of these compounds have been identified and quantified. In this study data are evaluated regarding differences in the micronucleus frequency of human erythrocytes (fMNs) in peripheral blood (a known biomarker of genotoxicity) in individuals that consumed either high- or low-heated food during a 4-day period. Concomitantly, acrylamide (aa) levels were measured in the food that the participants consumed. The obtained fMNs in this human study are compared with the fMNs in mice after comparable exposure levels of pure aa. The results of this comparison showed several hundred times higher fMNs in humans compared with mice. With an assumed linear correlation between an increased genotoxic effect and cancer, our data suggest that aa only represents a fraction of all carcinogenic compounds produced in heated carbohydrate-rich food. Consequently, our daily intake of carbohydrate-rich food heated at high temperatures might be responsible for one-fifth of the rate of the total cancer risk. One sentence summary: A biomarker of genotoxicity indicates the risk of cancer to be some hundred-fold greater in heated carbohydrate-rich food than the risk calculated from animal studies on pure acrylamide.

  • 29.
    Abramsson-Zetterberg, Lilianne
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Ilback, Nils-Gunnar
    The synthetic food colouring agent Allura Red AC (E129) is not genotoxic in a flow cytometry-based micronucleus assay in vivo2013Inngår i: Food and Chemical Toxicology, ISSN 0278-6915, E-ISSN 1873-6351, Vol. 59, s. 86-89Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The safety of several azo colouring agents, used as food additives, has during the years been questioned. Allura Red AC (E129) has in some publications been classified as genotoxic. In fact, in the European Union, Allura Red is permitted as a food additive in human food, but, surprisingly, it was not acceptable as an additive for use in animal feed. In this study we have evaluated whether Allura Red is genotoxic using a flow cytometer-based micronucleus assay in peripheral blood of mice. Male FVB mice were given a single intra-peritoneal injection of various doses of Allura Red and sacrificed at 46 h after treatment. The tested doses were 0, 100, 200, 400, 600, 800, 1000, 1500, and 2000 mg/kg body weight (b.w.). Each dose group constituted three mice, except for in the dose group of 1000 mg/kg b.w., which constituted four mice. Blood samples were collected and the frequency of micronucleated polychromatic erythrocytes (fMNPCE) and the cell proliferation (%PCE) was determined. The analyses did not show any significant difference in the %PCE or in the fMNPCE. Consequently, under the testing circumstances one can conclude that Allura Red is not genotoxic.

  • 30.
    Abreu-Vieira, Gustavo
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Thermal physiology and metabolism: Interplay between heat generation and energy homeostasis2015Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Mammal metabolism is intimately connected to the maintenance of body temperature. While metabolic pathways invariably produce heat as a by-product, the natural heat present in the environment also plays a role in defining the adaptive metabolism and general physiology of an organism. This thesis aims to discuss basic aspects of energy expenditure and their interactions with energy stores and body composition. In Paper I, we apply a new technique – high-resolution laser-Doppler imaging – to describe physiological regulatory features of adrenergically-stimulated blood flow in brown adipose tissue, and evaluate the validity of blood flow as a parameter to estimate nonshivering thermogenesis. Paper II focuses on the central regulation of body temperature. In the absence of bombesin receptor subtype-3, mice present an altered neurological body temperature setpoint, while peripheral thermogenic capacity remains intact. We conclude that brown adipose tissue malfunction is not the cause of the hypothermia observed in this mouse model. Paper III incorporates measurements of body temperature to the energy expenditure of different sources: basal metabolic rate, physical activity, thermic effect of food, and cold-induced thermogenesis. We describe basic aspects of dynamic insulation, energetic costs of circadian variation and hypothesize that physical activity may change the body temperature setpoint. Paper IV describes methodological issues related to glucose tolerance tests in obese mice. We conclude that the erroneous scaling of doses may affect the interpretation of metabolic health in mouse models, and suggest a new methodology. Paper V describes the outcomes caused by the expression of the human Cidea protein in adipose tissue of mice and suggests that this protein may clarify the link between adipose tissue expansion and healthy obesity. Paper VI explores the dissociation between thiazolidinedione-induced adipose tissue “browning” and reduced blood glycaemia. We demonstrate that although this pharmacological class tends to induce some level of brown adipose tissue recruitment, this phenomenon does not define its antidiabetic effects.

    Fulltekst (pdf)
    fulltext
    Download (jpg)
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  • 31.
    Abreu-Vieira, Gustavo
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Fischer, Alexander W.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. University of Hamburg, Germany.
    Mattsson, Charlotte
    de Jong, Jasper M. A.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Shabalina, Irina G.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Ryden, Mikael
    Laurencikiene, Jurga
    Arner, Peter
    Cannon, Barbara
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Nedergaard, Jan
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Petrovic, Natasa
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Cidea improves the metabolic profile through expansion of adipose tissue2015Inngår i: Nature Communications, E-ISSN 2041-1723, Vol. 6, artikkel-id 7433Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In humans, Cidea (cell death-inducing DNA fragmentation factor alpha-like effector A) is highly but variably expressed in white fat, and expression correlates with metabolic health. Here we generate transgenic mice expressing human Cidea in adipose tissues (aP2-hCidea mice) and show that Cidea is mechanistically associated with a robust increase in adipose tissue expandability. Under humanized conditions (thermoneutrality, mature age and prolonged exposure to high-fat diet), aP2-hCidea mice develop a much more pronounced obesity than their wild-type littermates. Remarkably, the malfunctioning of visceral fat normally caused by massive obesity is fully overcome-perilipin 1 and Akt expression are preserved, tissue degradation is prevented, macrophage accumulation is decreased and adiponectin expression remains high. Importantly, the aP2-hCidea mice display enhanced insulin sensitivity. Our data establish a functional role for Cidea and suggest that, in humans, the association between Cidea levels in white fat and metabolic health is not only correlative but also causative.

  • 32.
    Abreu-Vieira, Gustavo
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Kalinovich, Anastasia
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Cannon, Barbara
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Nedergaard, Jan
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Novel thiazolidinediones distinguish between (UCP1-independent) antidiabetic effects (MSDC-0602) and adipogenic and browning-inducing effects (MSDC-0160) of classical thiazolidinediones (rosiglitazone)Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Thiazolinediones (TZDs), also called glitazones, are a class of drugs traditionally used forimproving glucose tolerance in type II diabetes mellitus. The beneficial effects ofthiazolidinedione are believed to be caused by the drug binding to the nuclear receptor PPARγ,which in turn triggers a general adipogenic program in white adipose tissue, and apparentthermogenic recruitment of brown and brite/beige fat. Here, we present a comparison of thephysiological effects of three thiazolidinediones (rosiglitazone, MSDC-0602, and MSDC-0160)in C57BL/6 mice fed high-fat diet and housed at thermoneutrality. Rosiglitazone and MSDC-0160 caused the classically-described thiazolidinedione effects of increased fat mass,hyperphagia, and increased UCP1 levels in brown adipose tissue. MSDC-0602 and rosiglitazoneimproved glucose tolerance but MSDC-0602 did not induce increased fat mass, hyperphagia, orincreased UCP1 levels in brown fat. The beneficial effects of thiazolidinediones were fullypresent even in UCP1-KO mice, providing evidence for a dissociation between thiazolidinedioneinducedadipose tissue browning and their antidiabetic effects. We conclude that even structurallysimilar thiazolidinediones can act through distinct pathways, and that the glucose-loweringeffects of this class do not seem to rely on PPAR-γ-induced browning of adipose tissues.

  • 33. Acevedo, Nathalie
    et al.
    Benfeitas, Rui
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik. Stockholms universitet, Science for Life Laboratory (SciLifeLab).
    Katayama, Shintaro
    Bruhn, Sören
    Andersson, Anna
    Wikberg, Gustav
    Lundeberg, Lena
    Lindvall, Jessica M.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik. Stockholms universitet, Science for Life Laboratory (SciLifeLab).
    Greco, Dario
    Kere, Juha
    Söderhäll, Cilla
    Scheynius, Annika
    Epigenetic alterations in skin homing CD4(+)CLA(+) T cells of atopic dermatitis patients2020Inngår i: Scientific Reports, E-ISSN 2045-2322, Vol. 10, nr 1, artikkel-id 18020Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    T cells expressing the cutaneous lymphocyte antigen (CLA) mediate pathogenic inflammation in atopic dermatitis (AD). The molecular alterations contributing to their dysregulation remain unclear. With the aim to elucidate putative altered pathways in AD we profiled DNA methylation levels and miRNA expression in sorted T cell populations -(CD4(+), -CD4(+)CD45RA(+) naive, -CD4(+)CLA(+), and -CD8(+)) from adult AD patients and healthy controls (HC). Skin homing -CD4(+)CLA(+) T cells from AD patients showed significant differences in DNA methylation in 40 genes compared to HC (p < 0.05). Reduced DNA methylation levels in the upstream region of the interleukin-13 gene (IL13) in -CD4(+)CLA(+) T cells from AD patients correlated with increased IL13 mRNA expression in these cells. Sixteen miRNAs showed differential expression in -CD4(+)CLA(+) T cells from AD patients targeting genes in 202 biological processes (p < 0.05). An integrated network analysis of miRNAs and CpG sites identified two communities of strongly interconnected regulatory elements with strong antagonistic behaviours that recapitulated the differences between AD patients and HC. Functional analysis of the genes linked to these communities revealed their association with key cytokine signaling pathways, MAP kinase signaling and protein ubiquitination. Our findings support that epigenetic mechanisms play a role in the pathogenesis of AD by affecting inflammatory signaling molecules in skin homing -CD4(+)CLA(+) T cells and uncover putative molecules participating in AD pathways.

  • 34. Acevedo, Nathalie
    et al.
    Bornacelly, Adriana
    Mercado, Dilia
    Unneberg, Per
    Stockholms universitet, Science for Life Laboratory (SciLifeLab). Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Mittermann, Irene
    Valenta, Rudolf
    Kennedy, Malcolm
    Scheynius, Annika
    Caraballo, Luis
    Genetic Variants in CHIA and CHI3L1 Are Associated with the IgE Response to the Ascaris Resistance Marker ABA-1 and the Birch Pollen Allergen Bet v 12016Inngår i: plos one, ISSN 1932-6203, Vol. 11, nr 12, artikkel-id e0167453Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Helminth infections and allergic diseases are associated with IgE hyperresponsiveness but the genetics of this phenotype remain to be defined. Susceptibility to Ascaris lumbricoides infection and antibody levels to this helminth are associated with polymorphisms in locus 13q33-34. We aimed to explore this and other genomic regions to identify genetic variants associated with the IgE responsiveness in humans. Forty-eight subjects from Cartagena, Colombia, with extreme values of specific IgE to Ascaris and ABA-1, a resistance marker of this nematode, were selected for targeted resequencing. Burden analyses were done comparing extreme groups for IgE values. One-hundred one SNPs were genotyped in 1258 individuals of two well-characterized populations from Colombia and Sweden. Two low-frequency coding variants in the gene encoding the Acidic Mammalian Chitinase (CHIA rs79500525, rs139812869, tagged by rs10494133) were found enriched in high IgE responders to ABA-1 and confirmed by genetic association analyses. The SNP rs4950928 in the Chitinase 3 Like 1 gene (CHI3L1) was associated with high IgE to ABA-1 in Colombians and with high IgE to Bet v 1 in the Swedish population. CHIA rs10494133 and ABDH13 rs3783118 were associated with IgE responses to Ascaris. SNPs in the Tumor Necrosis Factor Superfamily Member 13b gene (TNFSF13B) encoding the cytokine B cell activating Factor were associated with high levels of total IgE in both populations. This is the first report on the association between low-frequency and common variants in the chitinases- related genes CHIA and CHI3L1 with the intensity of specific IgE to ABA-1 in a population naturally exposed to Ascaris and with Bet v 1 in a Swedish population. Our results add new information about the genetic influences of human IgE responsiveness; since the genes encode for enzymes involved in the immune response to parasitic infections, they could be helpful for understanding helminth immunity and allergic responses. We also confirmed that TNFSF13B has an important and conserved role in the regulation of total IgE levels, which supports potential evolutionary links between helminth immunity and allergic response.

  • 35. Acevedo, Nathalie
    et al.
    Scala, Giovanni
    Kebede Merid, Simon
    Frumento, Paolo
    Bruhn, Sören
    Andersson, Anna
    Ogris, Christoph
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik. Stockholms universitet, Science for Life Laboratory (SciLifeLab). Helmholtz Center Munich, Germany.
    Bottai, Matteo
    Pershagen, Göran
    Koppelman, Gerard H.
    Melén, Erik
    Sonnhammer, Erik
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik. Stockholms universitet, Science for Life Laboratory (SciLifeLab).
    Alm, Johan
    Söderhäll, Cilla
    Kere, Juha
    Greco, Dario
    Scheynius, Annika
    DNA Methylation Levels in Mononuclear Leukocytes from the Mother and Her Child Are Associated with IgE Sensitization to Allergens in Early Life2021Inngår i: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, nr 2, artikkel-id 801Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    DNA methylation changes may predispose becoming IgE-sensitized to allergens. We analyzed whether DNA methylation in peripheral blood mononuclear cells (PBMC) is associated with IgE sensitization at 5 years of age (5Y). DNA methylation was measured in 288 PBMC samples from 74 mother/child pairs from the birth cohort ALADDIN (Assessment of Lifestyle and Allergic Disease During INfancy) using the HumanMethylation450BeadChip (Illumina). PBMCs were obtained from the mothers during pregnancy and from their children in cord blood, at 2 years and 5Y. DNA methylation levels at each time point were compared between children with and without IgE sensitization to allergens at 5Y. For replication, CpG sites associated with IgE sensitization in ALADDIN were evaluated in whole blood DNA of 256 children, 4 years old, from the BAMSE (Swedish abbreviation for Children, Allergy, Milieu, Stockholm, Epidemiology) cohort. We found 34 differentially methylated regions (DMRs) associated with IgE sensitization to airborne allergens and 38 DMRs associated with sensitization to food allergens in children at 5Y (Sidak p <= 0.05). Genes associated with airborne sensitization were enriched in the pathway of endocytosis, while genes associated with food sensitization were enriched in focal adhesion, the bacterial invasion of epithelial cells, and leukocyte migration. Furthermore, 25 DMRs in maternal PBMCs were associated with IgE sensitization to airborne allergens in their children at 5Y, which were functionally annotated to the mTOR (mammalian Target of Rapamycin) signaling pathway. This study supports that DNA methylation is associated with IgE sensitization early in life and revealed new candidate genes for atopy. Moreover, our study provides evidence that maternal DNA methylation levels are associated with IgE sensitization in the child supporting early in utero effects on atopy predisposition.

  • 36. Acheva, Anna
    et al.
    Haghdoost, Siamak
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. University of Caen Normandy, France.
    Sollazzo, Alice
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Launonen, Virpi
    Kamarainen, Meerit
    Presence of Stromal Cells Enhances Epithelial-to-Mesenchymal Transition (EMT) Induction in Lung Bronchial Epithelium after Protracted Exposure to Oxidative Stress of Gamma Radiation2019Inngår i: Oxidative Medicine and Cellular Longevity, ISSN 1942-0900, E-ISSN 1942-0994, Vol. 2019, artikkel-id 4120379Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aim of the study was to investigate the role of a microenvironment in the induction of epithelial-to-mesenchymal transition (EMT) as a sign of early stages of carcinogenesis in human lung epithelial cell lines after protracted low-dose rate gamma-radiation exposures. BEAS-2B and HBEC-3KT lung cell lines were irradiated with low-dose rate gamma-rays (Cs-137, 1.4 or 14 mGy/h) to 0.1 or 1 Gy with or without adding TGF-beta. TGF-beta-treated samples were applied as positive EMT controls and tested in parallel to find out if the radiation has a potentiating effect on the EMT induction. To evaluate the effect of the stromal component, the epithelial cells were irradiated in cocultures with stromal MRC-9 lung fibroblasts. On day 3 post treatment, the EMT markers: alpha-SMA, vimentin, fibronectin, and E-cadherin, were analyzed. The oxidative stress levels were evaluated by 8-oxo-dG analysis in both epithelial and fibroblast cells. The protracted exposure to low Linear Energy Transfer (LET) radiation at the total absorbed dose of 1 Gy was able to induce changes suggestive of EMT. The results show that the presence of the stromal component and its signaling (TGF-beta) in the cocultures enhances the EMT. Radiation had a minor cumulative effect on the TGF-beta-induced EMT with both doses. The oxidative stress levels were higher than the background in both epithelial and stromal cells post chronic irradiation (0.1 and 1 Gy); as for the BEAS-2B cell line, the increase was statistically significant. We suggest that the induction of EMT in bronchial epithelial cells by radiation requires more than single acute exposure and the presence of stromal component might enhance the effect through free radical production and accumulation.

  • 37.
    Adam, Lucille
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    López-González, Moisés
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Björk, Albin
    Pålsson, Sandra
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Poux, Candice
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Wahren-Herlenius, Marie
    Fernández, Carmen
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Spetz, Anna-Lena
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Early Resistance of Non-virulent Mycobacterial Infection in C57BL/6 Mice Is Associated With Rapid Up-Regulation of Antimicrobial Cathelicidin Camp2018Inngår i: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 9, artikkel-id 1939Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Early clearance of tuberculosis is the successful eradication of inhaled bacteria before the development of an adaptive immune response. We previously showed, by utilizing a non-virulent mycobacteria infection model, that C57BL/6 mice are more efficient than BALB/c in their control of bacterial growth in the lungs during the first weeks of the infection. Here, we assessed early (within 1-3 days) innate immune events locally in the lungs to identify factors that may contribute to the control of non-virulent mycobacterial burden. We confirmed that C57BL/6 mice are more resistant to infection compared with BALB/c after intranasal inoculation with mycobacterium. Transcriptomic analyses revealed a remarkably silent signature in C57BL/6 mice despite effective control of bacterial growth. In contrast, BALB/c mice up-regulated genes associated with neutrophil and myeloid cell chemotaxis and migration. Flow cytometry analyses corroborated the transcriptomic analyses and demonstrated influx of both neutrophil and myeloid cell populations in BALB/c mice, while these did not increase in C57BL/6 mice. We further detected increased release of TNF-alpha from BALB/c lung cells but limited release from C57BL/6-derived cells. However, C57BL/6 mice showed a marked early up-regulation of the Camp gene, encoding the cathelicidin CRAMP peptide, post-mycobacterial exposure. CRAMP (LL-37 in human) expression in the lungs was confirmed using immunofluorescence staining. Altogether, these findings show that C57BL/6 mice can clear the mycobacterial infection early and that this early control is associated with high CRAMP expression in the lungs without concomitant influx of immune cells. The role of CRAMP/LL-37 during mycobacterial infection may be relevant for novel protective strategies, and warrants further studies of human cohorts.

  • 38. Adam, Lucille
    et al.
    Tchitchek, Nicolas
    Todorova, Biliana
    Rosenbaum, Pierre
    Joly, Candie
    Poux, Candice
    Chapon, Catherine
    Spetz, Anna-Lena
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Ustav, Mart
    Le Grand, Roger
    Martinon, Frédéric
    Innate Molecular and Cellular Signature in the Skin Preceding Long-Lasting T Cell Responses after Electroporated DNA Vaccination2020Inngår i: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 204, nr 12, s. 3375-3388Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    DNA vaccines delivered with electroporation (EP) have shown promising results in preclinical models and are evaluated in clinical trials. In this study, we aim to characterize early mechanisms occurring in the skin after intradermal injection and EP of the auxoGTUmultiSIV DNA vaccine in nonhuman primates. First, we show that EP acts as an adjuvant by enhancing local inflammation, notably via granulocytes, monocytes/macrophages, and CD1a(int)-expressing cell recruitment. EP also induced Langerhans cell maturation, illustrated by CD86, CD83, and HLA-DR upregulation and their migration out of the epidermis. Second, we demonstrate the crucial role of the DNA vaccine in soluble factors release, such as MCP-1 or IL-15. Transcriptomic analysis showed that EP played a major role in gene expression changes postvaccination. However, the DNA vaccine is required to strongly upregulate several genes involved in inflammatory responses (e.g., Saa4), cell migration (e.g., Ccl3, Ccl5, or Cxcl10), APC activation (e.g., Cd86), and IFN-inducible genes (e.g., Ifit3, Ifit5, Irf7, Isg15, orMx1), illustrating an antiviral response signature. Also, AIM-2, a cytosolic DNA sensor, appeared to be strongly upregulated only in the presence of the DNA vaccine and trends to positively correlate with several IFN-inducible genes, suggesting the potential role of AIM-2 in vaccine sensing and the subsequent innate response activation leading to strong adaptive T cell responses. Overall, these results demonstrate that a combined stimulation of the immune response, in which EP and the auxoGTUmultiSIV vaccine triggered different components of the innate immunity, led to strong and persistent cellular recall responses.

  • 39. Adams, Jimi
    et al.
    Lawrence, Elizabeth M.
    Goode, Joshua A.
    Schaefer, David R.
    Möllborn, Stefanie
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Sociologiska institutionen. University of Colorado Boulder, USA.
    Peer Network Processes in Adolescents' Health Lifestyles2022Inngår i: Journal of health and social behavior, ISSN 0022-1465, E-ISSN 2150-6000, Vol. 63, nr 1, s. 125-141Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Combining theories of health lifestyles-interrelated health behaviors arising from group-based identities-with those of network and behavior change, we investigated network characteristics of health lifestyles and the role of influence and selection processes underlying these characteristics. We examined these questions in two high schools using longitudinal, complete friendship network data from the National Longitudinal Study of Adolescent to Adult Health. Latent class analyses characterized each school's predominant health lifestyles using several health behavior domains. School-specific stochastic actor-based models evaluated the bidirectional relationship between friendship networks and health lifestyles. Predominant lifestyles remained stable within schools over time, even as individuals transitioned between lifestyles. Friends displayed greater similarity in health lifestyles than nonfriend dyads. Similarities resulted primarily from teens' selection of friends with similar lifestyles but also from teens influencing their peers' lifestyles. This study demonstrates the salience of health lifestyles for adolescent development and friendship networks.

  • 40. Adams, John
    et al.
    Pike, Tim
    Corna, Laurie M.
    Platts, Loretta G.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Stressforskningsinstitutet.
    Worts, Diana
    McDonough, Peggy
    Di Gessa, Giorgio
    Sacker, Amanda
    Glaser, Karen
    Price, Debora
    How do female lifecourses affect income in retirement?2016Rapport (Annet vitenskapelig)
    Abstract [en]

    This Briefing Note examines the influence of various lifecourses on income in retirement. The primary focus of this note is to consider how women’s retirement income is affected by motherhood. This includes the impact of taking time out of work to care for children, as well as the implications of the Motherhood Penalty, which is the observation that mothers tend to have reduced incomes relative to women without children.

    Fulltekst (pdf)
    fulltext
  • 41. Adams, Rick A.
    et al.
    Moutoussis, Michael
    Nour, Matthew M.
    Dahoun, Tarik
    Lewis, Declan
    Illingworth, Benjamin
    Veronese, Mattia
    Mathys, Christoph
    de Boer, Lieke
    Guitart-Masip, Marc
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI). Max Planck-UCL Centre for Computational Psychiatry and Ageing Research, UK.
    Friston, Karl J.
    Howes, Oliver D.
    Roiser, Jonathan P.
    Variability in Action Selection Relates to Striatal Dopamine 2/3 Receptor Availability in Humans: A PET Neuroimaging Study Using Reinforcement Learning and Active Inference Models2020Inngår i: Cerebral Cortex, ISSN 1047-3211, E-ISSN 1460-2199, Vol. 30, nr 6, s. 3573-3589Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Choosing actions that result in advantageous outcomes is a fundamental function of nervous systems. All computational decision-making models contain a mechanism that controls the variability of (or confidence in) action selection, but its neural implementation is unclear-especially in humans. We investigated this mechanism using two influential decision-making frameworks: active inference (AI) and reinforcement learning (RL). In AI, the precision (inverse variance) of beliefs about policies controls action selection variability-similar to decision 'noise' parameters in RL-and is thought to be encoded by striatal dopamine signaling. We tested this hypothesis by administering a 'go/no-go' task to 75 healthy participants, and measuring striatal dopamine 2/3 receptor (D2/3R) availability in a subset (n = 25) using [C-11]-(+)-PHNO positron emission tomography. In behavioral model comparison, RL performed best across the whole group but AI performed best in participants performing above chance levels. Limbic striatal D2/3R availability had linear relationships with AI policy precision (P = 0.029) as well as with RL irreducible decision 'noise' (P = 0.020), and this relationship with D2/3R availability was confirmed with a 'decision stochasticity' factor that aggregated across both models (P = 0.0006). These findings are consistent with occupancy of inhibitory striatal D(2/3)Rs decreasing the variability of action selection in humans.

  • 42.
    Adamus-Gorka, Magdalena
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Medicinsk strålningsfysik (tills m KI).
    Mavroidis, Panayiotis
    Stockholms universitet, Naturvetenskapliga fakulteten, Medicinsk strålningsfysik (tills m KI).
    Brahme, Anders
    Stockholms universitet, Naturvetenskapliga fakulteten, Medicinsk strålningsfysik (tills m KI).
    Lind, Bengt K
    Stockholms universitet, Naturvetenskapliga fakulteten, Medicinsk strålningsfysik (tills m KI).
    An “Effective functional subunit size” model for the dose response of rat spinal cord paralysis2007Inngår i: 13th International Congress of Radiation Research, San Fransisco, USA, July 8-12, 2007, 2007Konferansepaper (Annet (populærvitenskap, debatt, mm))
    Abstract [en]

    Background: Radiobiological models for normal tissue complication probability (NTCP) are more and more commonly used in order to estimate the clinical outcome of radiation therapy. A normal tissue complication probability model to be considered a good and reliable one should fulfill the following two requirements: (a) it should predict the sigmoid shape of the dose-response curve as well as possible and (b) it should duly handle the volume effect. In the work from 2005 (IJROBP 61(3):892-900, 2005) P. van Luijk et al. suggest that none of the existing NTCP models is able to describe the volume effects present in the rat spinal cord during irradiation with small proton beams and they indicate the need for developing such new models.

    Methods: We have used the experimental data from H. Bijl et al. (IJROBP 52(1):205-211, 2002) to try explaining the change in the fifty percent effective dose (ED50) for different field sizes. We initiated this study to evaluate whether the induction of white matter necrosis in rat spinal cord after irradiation with small proton beams could be explained independent of used NTCP model. We therefore introduced a new concept of effective FSU dose, where a convolution of the original dose distribution with a function describing the effective size of a single FSU results in the average doses in a functional subunit. Such procedure allows determining the ED50 in an FSU of a certain size, within the irradiation field. We have also looked at non uniform dose distributions to see whether using a similar method we can explain the so called “bath and shower experiments” (IJROBP 57(1): 274-281, 2003).

    Results: Using the least square method to compare the effective doses for different sizes of functional subunits with the experimental data we observe the best fit for about 8 mm length. It seems that this length could be understood as an effective size of functional subunits in rat spinal cord, explaining what is otherwise interpreted as a volume effect. For the non uniform dose distributions an effective FSU length of 5 mm gives the optimal fit with the Probit dose-response model.

    Conclusions: The concept of an effective FSU length seems to explain at least part of the effects seen when small portions of the rat spinal cord are irradiated. The most likely FSU length for the shower and bath experiments is 5 mm according to these calculations.

  • 43.
    Addo, Rebecka N.
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Perception och psykofysik. Uppsala University, Sweden.
    Wiens, Stefan
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Perception och psykofysik.
    Nord, Marie
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Perception och psykofysik.
    Larsson, Maria
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen, Perception och psykofysik.
    Olfactory Functions in Adults With Autism Spectrum Disorders2017Inngår i: Perception, ISSN 0301-0066, E-ISSN 1468-4233, Vol. 46, nr 3-4, s. 530-537Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Autism spectrum disorders (ASD) are often characterized by atypical sensory behavior (hyperor hyporeactivity) although evidence is scarce regarding olfactory abilities in ASD; 16 adults with high-functioning ASD (mean age: 38.2, SD: 9.7) and 14 healthy control subjects (mean age: 42.0 years, SD: 12.5) were assessed in odor threshold, free and cued odor identification, and perceived pleasantness, intensity, and edibility of everyday odors. Although results showed no differences between groups, the Bayes Factors (close to 1) suggested that the evidence for no group differences on the threshold and identification tests was inconclusive. In contrast, there was some evidence for no group differences on perceived edibility (BF01 = 2.69) and perceived intensity (BF01 = 2.80). These results do not provide conclusive evidence for or against differences between ASD and healthy controls on olfactory abilities. However, they suggest that there are no apparent group differences in subjective ratings of odors.

  • 44. Adia, Madina Mohamed
    et al.
    Emami, Seyedeh Noushin
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Byamukama, Robert
    Faye, Ingrid
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Borg-Karlson, Anna-Karin
    Antiplasmodial activity and phytochemical analysis of extracts from selected Ugandan medicinal plants2016Inngår i: Journal of Ethnopharmacology, ISSN 0378-8741, E-ISSN 1872-7573, Vol. 186, s. 14-19Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Ethnopharmacological relevance: Resistance of the parasites to known antimalarial drugs has provided the necessity to find new drugs from natural products against malaria. The aim of the study was to evaluate the in vitro antiplasmodial activity of some plants used by Traditional Medical Practitioners (TMPs) of Prometra and Rukararwe in malaria treatment in Uganda to provide scientific proof of the efficacies claimed by these Herbalists.

    Materials and methods: The air dried samples of Clerodendrum rotundifolium (leaves), Microglossa pyrifolia (leaves), Momordica foetida (leaves) and Zanthoxylum chalybeum (stem bark) used for malaria treatment by TMPs were successively extracted with ethyl acetate, methanol and water to yield twelve extracts. The extracts were tested against the chloroquine-sensitive (NF54) and chloroquine-resistant (FCR3) Plasmodium falciparum strains in vitro using the micro Mark III test which is based on assessing the inhibition of schizont maturation. A compound A was extracted and purified from the stem bark of Z. chalybeum and its structure was identified and confirmed by spectroscopic methods.

    Results: Most of the extracts tested (92%) showed an antiplasmodial activity with IC50 < 50 mu g/mL. In spite of successive extractions with different solvents, potent anti-plasmodial activity (IC50 < 5 mu g/mL) was observed in the ethyl acetate, methanol and aqueous extracts of M. pyrifolia and C. rotundifolium. Preferential enrichments of activity into water (IC50 < 15 mu g/mL) and Ethyl acetate (IC50 < 5 mu g/mL) were seen in the case of M. foetida and Z chalybeum respectively. The most active extracts were from C rotundifolium and M. pyrifolia with IC50 values less than 2 mu g/mL. Phytochemical analysis of the extracts revealed the presence of saponins, tannins, flavonoids, alkaloids and cardiac glycocides. Fagaramide isolated from Z chalybeum had a higher activity (IC50 2.85 mu g/mL) against the chloroquine-resistant strain than against the chloroquine-senstive (IC50 16.6 mu g/mL) strain used in the study.

    Conclusion: The plant extracts analysed in this study presented an average antiplasmodial activity (58%). This study revealed for the first time the antiplasmodial activity of the plant C. rotundofolium. It's the first time the compound fagaramide (N-isobutyl-3-(3,4-methylene dioxyphenyl) - 2E-propenamide) has been isolated from Z. chalybeum as one of the compounds that contribute to the activity of this plant against P. falciparum.

  • 45. Adjei, Nicholas Kofi
    et al.
    Jonsson, Kenisha Russell
    Schultz Straatmann, Viviane
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för folkhälsovetenskap.
    Melis, Gabriella
    McGovern, Ruth
    Kaner, Eileen
    Wolfe, Ingrid
    Taylor-Robinson, David C.
    Impact of poverty and adversity on perceived family support in adolescence: findings from the UK Millennium Cohort Study2024Inngår i: European Child and Adolescent Psychiatry, ISSN 1018-8827, E-ISSN 1435-165XArtikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Emotional support from family members may have an important effect on adolescent health outcomes, and has been identified as a target for policy to protect against the impacts of poverty and other early life adversities. However, few studies have assessed the extent to which poverty and adversity themselves influence the nature of emotional support that parents can provide to adolescents. We, therefore, aimed to investigate the impact of trajectories of income poverty and family adversities, including parental mental ill health, alcohol misuse and domestic violence across childhood developmental stages on young people’s relationships with their families and perceived emotional support received. We analysed longitudinal data on 10,976 children from the nationally representative UK Millennium Cohort study. Exposure trajectories of poverty and family adversities were characterised using group-based multi-trajectory models (age 9 months–14 years). The outcomes were perceived emotional support and quality of family relationships, measured by the three-item Short Social Provisions Scale (SPS-3) and levels of parent–adolescent closeness and conflict, measured at age 14. ORs and 95% CIs were estimated using multivariable logistic regression models, adjusting for potential confounding factors. At age 14, the overall prevalence of low perceived emotional support was 13% (95% CI: 12, 14). Children of mothers with lower socioeconomic status (SES) were more likely to report low emotional support, with a clear social gradient (education—degree plus: 10.3% vs. no qualifications: 15.4%). Compared with children exposed to low levels of poverty and adversity, children in the persistent adversity trajectory groups experienced higher odds of low emotional support and low-quality parent–adolescent relationship; those exposed to both persistent poverty and poor parental mental health were particularly at increased risk of experiencing poor family relationships and low perceived emotional support (adjusted odds ratio 2·2; 95% CI 1·7–2·9). Low perceived emotional support and poor family relationships in adolescence are more prevalent among socially disadvantaged children and adolescents and those experiencing social adversity. Policies to improve levels of family support for UK adolescents should focus on improving modifiable determinants such as child poverty and family mental health. 

  • 46. Adjei, Nicholas Kofi
    et al.
    Schlüter, Daniela K.
    Melis, Gabriella
    Schultz Straatmann, Viviane
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för folkhälsovetenskap.
    Fleming, Kate M.
    Wickham, Sophie
    Munford, Luke
    McGovern, Ruth
    Howard, Louise M.
    Kaner, Eileen
    Wolfe, Ingrid
    Taylor-Robinson, David C.
    Impact of Parental Mental Health and Poverty on the Health of the Next Generation: A Multi-Trajectory Analysis Using the UK Millennium Cohort Study2024Inngår i: Journal of Adolescent Health, ISSN 1054-139X, E-ISSN 1879-1972, Vol. 74, nr 1, s. 60-70Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: Exposure to parental mental ill-health and poverty in childhood impact health across the lifecourse. Both maternal and paternal mental health may be important influences, but few studies have unpicked the complex interrelationships between these exposures and family poverty for later health.

    Methods: We used longitudinal data on 10,500 children from the nationally representative UK millennium cohort study. Trajectories of poverty, maternal mental health, and secondary caregiver mental health were constructed from child age of 9 months through to 14 years. We assessed the associations of these trajectories with mental health outcomes at the age of 17 years. Population-attributable fractions were calculated to quantify the contribution of caregivers' mental health problems and poverty to adverse outcomes at the country level.

    Results: We identified five distinct trajectories. Compared with children with low poverty and good parental mental health, those who experienced poverty and poor primary or secondary caregiver mental health (53%) had worse outcomes. Children exposed to both persistent poverty and poor caregiver mental health were at markedly increased risk of socioemotional behavioural problems (aOR 4.2; 95% CI 2.7–6.7), mental health problems (aOR 2.5; CI 1.6–3.9), and cognitive disability (aOR 1.7; CI 1.1–2.5). We estimate that 40% of socioemotional behavioural problems at the age of 17 were attributable to persistent parental caregivers' mental health problems and poverty.

    Discussion: More than half of children growing up in the UK are persistently exposed to either one or both of poor caregiver mental health and family poverty. The combination of these exposures is strongly associated with adverse health outcomes in the next generation.

  • 47. Adjei, Nicholas Kofi
    et al.
    Schlüter, Daniela K.
    S. Straatmann, Viviane
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för folkhälsovetenskap.
    Melis, Gabriella
    Fleming, Kate M.
    McGovern, Ruth
    Howard, Louise M.
    Kaner, Eileen
    Wolfe, Ingrid
    Taylor-Robinson, David C.
    Impact of poverty and family adversity on adolescent health: a multi-trajectory analysis using the UK Millennium Cohort Study2022Inngår i: The Lancet Regional Health: Europe, E-ISSN 2666-7762, Vol. 13, artikkel-id 100279Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Children exposed to poverty and family adversities including domestic violence, parental mental ill health and parental alcohol misuse may experience poor outcomes across the life course. However, the complex interrelationships between these exposures in childhood are unclear. We therefore assessed the clustering of trajectories of household poverty and family adversities and their impacts on adolescent health outcomes.

    Methods We used longitudinal data from the UK Millennium Cohort study on 11564 children followed to age 14 years. Family adversities included parent reported domestic violence and abuse, poor mental health and frequent alcohol use. We used a group-based multi-trajectory cluster model to identify trajectories of poverty and family adversity for children. We assessed associations of these trajectories with child physical, mental and behavioural outcomes at age 14 years using multivariable logistic regression, adjusting for confounders.

    Findings Six trajectories were identified: low poverty and family adversity (43·2%), persistent parental alcohol use (7·7%), persistent domestic violence and abuse (3·4%), persistent poor parental mental health (11·9%), persistent poverty (22·6%) and persistent poverty and poor parental mental health (11·1%). Compared with children exposed to low poverty and adversity, children in the persistent adversity trajectory groups experienced worse outcomes; those exposed to persistent poor parental mental health and poverty were particularly at increased risk of socioemotional behavioural problems (adjusted odds ratio 6·4; 95% CI 5·0 – 8·3), cognitive disability (aOR 2·1; CI 1·5 – 2·8), drug experimentation (aOR 2·8; CI 1·8 – 4·2) and obesity (aOR 1·8; CI 1·3 – 2·5).

    Interpretation In a contemporary UK cohort, persistent poverty and/or persistent poor parental mental health affects over four in ten children. The combination of both affects one in ten children and is strongly associated with adverse child outcomes, particularly poor child mental health.

  • 48.
    Adlerz, Linda
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi.
    Processing of the amyloid precursor protein and its paralogues amyloid precursor-like proteins 1 and 22007Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Alzheimer’s disease (AD) is a neurodegenerative disorder which is histopathologically characterised by amyloid plaques and neurofibrillary tangles. Amyloid plaques consist of the amyloid β-peptide (Aβ) that can form aggregates in the brain. Aβ is generated from the amyloid precursor protein (APP) through proteolytic cleavage. APP belongs to a conserved protein family that also includes the two paralogues, APP-like proteins 1 and 2 (APLP1 and APLP2). Despite the immense amount of research on APP, motivated by its implication in AD, the function of this protein family has not yet been determined. In this thesis, we have studied the expression and proteolytic processing of the APP protein family. Our results are consistent with previous findings that suggest a role for APP during neuronal development. Treatment of cells with retinoic acid (RA) resulted in increased synthesis. In addition, we observed that RA treatment shifted the processing of APP from the amyloidogenic to the non-amyloidogenic pathway. The proteins in the APP family have been hard to distinguish both with respect to function and proteolytic processing. However, for development of new drugs with APP processing enzymes as targets this is of great importance. Our studies suggest similarities, but also differences in the mechanism regulating the processing of the different paralogues. We found that brain-derived neurotrophic factor (BDNF) had different impact on the members of the APP family. Most interestingly, we also found that the mechanism behind the increased processing in response to IGF-1 was not identical between the homologous proteins. In summary, our results indicate that in terms of regulation APLP1 and APLP2 differ more from each other than from APP. Our studies open up the possibility of finding means to selectively block Aβ production without interfering with the processing and function of the paralogous proteins.

    Fulltekst (pdf)
    FULLTEXT01
  • 49.
    Adlerz, Linda
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Beckman, Marie
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Holback, Sofia
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Tehranian, Roya
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Cortés Toro, Veronica
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Iverfeldt, Kerstin
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Accumulation of the amyloid precursor-like protein APLP2 and reduction of APLP1 in retinoic acid-differentiated human neuroblastoma cells upon curcumin-induced neurite retraction2003Inngår i: Brain Research. Molecular Brain Research, ISSN 0169-328X, E-ISSN 1872-6941, Vol. 119, nr 1, s. 62-72Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Amyloid precursor protein (APP) belongs to a conserved gene family, also including the amyloid precursor-like proteins, APLP1 and APLP2. The function of these three proteins is not yet fully understood. One of the proposed roles of APP is to promote neurite outgrowth. The aim of this study was to investigate the regulation of the expression levels of APP family members during neurite outgrowth. We observed that retinoic acid (RA)-induced neuronal differentiation of human SH-SY5Y cells resulted in increased expression of APP, APLP1 and APLP2. We also examined the effect of the NFκB, AP-1 and c-Jun N-terminal kinase inhibitor curcumin (diferuloylmethane) on the RA-induced expression levels of these proteins. We found that treatment with curcumin counteracted the RA-induced mRNA expression of all APP family members. In addition, we observed that curcumin treatment resulted in neurite retraction without any effect on cell viability. Surprisingly, curcumin had differential effects on the APLP protein levels in RA-differentiated cells. RA-induced APLP1 protein expression was blocked by curcumin, while the APLP2 protein levels were further increased. APP protein levels were not affected by curcumin treatment. We propose that the sustained levels of APP and the elevated levels of APLP2, in spite of the reduced mRNA expression, are due to altered proteolytic processing of these proteins. Furthermore, our results suggest that APLP1 does not undergo the same type of regulated processing as APP and APLP2.

  • 50.
    Adlerz, Linda
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Soomets, Ursel
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi. University of Tartu, Estonia.
    Holmlund, Linda
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Virland, Saade
    Langel, Ülo
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Iverfeldt, Kerstin
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för neurokemi och neurotoxikologi.
    Down-regulation of amyloid precursor protein by peptide nucleic acid oligomer in cultured rat primary neurons and astrocytes2003Inngår i: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 336, nr 1, s. 55-59Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The amyloid precursor protein (APP) and its proteolytic cleavage products, the amyloid P peptides, have been implicated as a cause of Alzheimer's disease. Peptide nucleic acids (PNA), the DNA mimics, have been shown to block the expression of specific proteins at both transcriptional and translational levels. Generally, the cellular uptake of PNA is low. However, recent studies have indicated that the effect of unmodified antisense PNA uptake is more pronounced in nervous tissue. In this study we have shown that biotinylated PNA directed to the initiator codon region of the APP mRNA (-4 - +11) was taken up into the cytoplasm of primary rat cerebellar granule cells and cortical astrocytes, using fluorescence and confocal microscopy studies. Uptake of PNA was faster in neurons than in astrocytes. Western blotting analysis showed that APP was strongly down-regulated in both neurons and astrocytes. Thus, unmodified PNA can be used for studies on the function of APP in neurons and astrocytes.

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