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| 2. |
- Behm, Mikaela, 1986-, et al.
(författare)
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Accumulation of nuclear ADAR2 regulates A-to-I RNA editing during neuronal development
- 2017
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Ingår i: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 130, s. 745-753
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Tidskriftsartikel (refereegranskat)abstract
- Adenosine to inosine (A-to-I) RNA editing is important for a functional brain, and most known sites that are subject to selective RNA editing have been found to result in diversified protein isoforms that are involved in neurotransmission. In the absence of the active editing enzymes ADAR1 or ADAR2 (also known as ADAR and ADARB1, respectively), mice fail to survive until adulthood. Nuclear A-to-I editing of neuronal transcripts is regulated during brain development, with low levels of editing in the embryo and a dramatic increase after birth. Yet, little is known about the mechanisms that regulate editing during development. Here, we demonstrate lower levels of ADAR2 in the nucleus of immature neurons than in mature neurons. We show that importin-a4 (encoded by Kpna3), which increases during neuronal maturation, interacts with ADAR2 and contributes to the editing efficiency by bringing it into the nucleus. Moreover, we detect an increased number of interactions between ADAR2 and the nuclear isomerase Pin1 as neurons mature, which contribute to ADAR2 protein stability. Together, these findings explain how the nuclear editing of substrates that are important for neuronal function can increase as the brain develops.
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| 3. |
- Berglind, Daniel, et al.
(författare)
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Longitudinal assessment of physical activity in women undergoing Roux-en-Y gastric bypass
- 2015
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Ingår i: Obesity Surgery. - : Springer Science and Business Media LLC. - 0960-8923 .- 1708-0428. ; 25:1, s. 119-125
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients undergoing bariatric surgery do not seem to increase objectively measured physical activity (PA) after surgery, despite substantial weight loss. The aims of the present study were (i) to objectively characterize 3 months pre-surgery to 9 months postsurgery PA and sedentary behavior changes in women undergoing Roux-en-Y gastric bypass (RYGB) using tri-axial accelerometers and (ii) to examine associations between pre-surgery versus postsurgery PA and sedentary behavior with anthropometric measures taken in home environment.Methods: Fifty-six women, with an average pre-surgery body mass index (BMI) of 37.6 (SD 2.6) and of age 39.5 years (SD 5.7), were recruited at five Swedish hospitals. PA was measured for 1 week by the Actigraph GT3X+ accelerometer, and anthropometric measures were taken at home visits 3 months pre-surgery and 9 months postsurgery, thus limiting seasonal effects.Results: Average BMI loss, 9 months postsurgery, was 11.7 (SD 2.7) BMI units. There were no significant pre- to postsurgery differences in PA or sedentary behavior. However, pre-surgery PA showed negative association with PA change and positive association with postsurgery PA. Adjustments for pre-surgery BMI had no impact on these associations.Conclusions: No significant differences were observed in objectively measured changes in PA or time spent sedentary from 3 months pre-surgery to 9 months postsurgery among women undergoing RYGB. However, women with higher pre-surgery PA decreased their PA postsurgery while women with lower pre-surgery PA increased their PA.
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| 6. |
- Friedman, Mikaela, et al.
(författare)
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Directed evolution to low nanomolar affinity of a tumor-targeting epidermal growth factor receptor-binding affibody molecule
- 2008
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 376:5, s. 1388-1402
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Tidskriftsartikel (refereegranskat)abstract
- The epidermal growth factor receptor 1 (EGFR) is overexpressed in various malignancies and is associated with a poor patient prognosis. A small, receptor-specific, high-affinity imaging agent would be a useful tool in diagnosing malignant tumors and in deciding upon treatment and assessing the response to treatment. We describe here the affinity maturation procedure for the generation of Affibody molecules binding with high affinity and specificity to EGFR. A library for affinity maturation was constructed by rerandomization of selected positions after the alignment of first-generation binding variants. New binders were selected with phage display technology, using a single oligonucleotide in a single-library effort, and the best second-generation binders had an approximately 30-fold improvement in affinity (K(d)=5-10 nM) for the soluble extracellular domain of EGFR in biospecific interaction analysis using Biacore. The dissociation equilibrium constant, K(d), was also determined for the Affibody with highest affinity using EGFR-expressing A431 cells in flow cytometric analysis (K(d)=2.8 nM). A retained high specificity for EGFR was verified by a dot blot assay showing staining only of EGFR proteins among a panel of serum proteins and other EGFR family member proteins (HER2, HER3, and HER4). The EGFR-binding Affibody molecules were radiolabeled with indium-111, showing specific binding to EGFR-expressing A431 cells and successful targeting of the A431 tumor xenografts with 4-6% injected activity per gram accumulated in the tumor 4 h postinjection.
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| 7. |
- Haapanen, Markus J., et al.
(författare)
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Early growth, stress, and socioeconomic factors as predictors of the rate of multimorbidity accumulation across the life course : a longitudinal birth cohort study
- 2024
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Ingår i: Lancet healthy longevity. - 2666-7568. ; 5:1, s. e56-e65
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early growth, stress, and socioeconomic factors are associated with future risk of individual chronic diseases. It is uncertain whether they also affect the rate of multimorbidity accumulation later in life. This study aimed to explore whether early life factors are associated with the rate at which chronic diseases are accumulated across older age.Methods: In this national birth cohort study, we studied people born at Helsinki University Central Hospital, Helsinki, Finland between Jan 1, 1934, and Dec 31, 1944, who attended child welfare clinics in the city, and were living in Finland in 1971. Individuals who had died or emigrated from Finland before 1987 were excluded, alongside participants without any registry data and who died before the end of the registry follow-up on Dec 31, 2017. Early anthropometry, growth, wartime parental separation, and socioeconomic factors were recorded from birth, child welfare clinic, or school health-care records, and Finnish National Archives. International Classification of Diseases codes of diagnoses for chronic diseases were obtained from the Care Register for Health Care starting from 1987 (when participants were aged 42-53 years) until 2017. Linear mixed models were used to study the association between early-life factors and the rate of change in the number of chronic diseases over 10-year periods.Findings: From Jan 1, 1934, to Dec 31, 2017, 11 689 people (6064 [51 center dot 9%] men and 5625 [48 center dot 1%] women) were included in the study. Individuals born to mothers younger than 25 years (beta 0 center dot 09; 95% CI 0 center dot 06-0 center dot 12), mothers with a BMI of 25-30 kg/m2 (0 center dot 08; 0 center dot 05-0 center dot 10), and mothers with a BMI more than 30 kg/m2 (0 center dot 26; 0 center dot 21-0 center dot 31) in late pregnancy accumulated chronic diseases faster than those born to older mothers (25-30 years) and those with a BMI of less than 25 kg/m2. Individuals with a birthweight less than 2 center dot 5 kg (0 center dot 17; 0 center dot 10-0 center dot 25) and those with a rapid growth in height and weight from birth until age 11 years accumulated chronic diseases faster during their life course. Additionally, paternal occupational class (manual workers vs upper-middle class 0 center dot 27; 0 center dot 23-0 center dot 30) and wartime parental separation (0 center dot 24; 0 center dot 19-0 center dot 29 for boys; 0 center dot 31; 0 center dot 25-0 center dot 36 for girls) were associated with a faster rate of chronic disease accumulation. Interpretation Our findings suggest that the foundation for accumulating chronic diseases is established early in life. Early interventions might be needed for vulnerable populations, including war evacuee children and children with lower socioeconomic status.
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| 8. |
- Hansson, Katarina, et al.
(författare)
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Sakområde Farliga Ämnen : Rapporteringskrav, omvärldsbeskrivning och framtida utmaningar
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Detta dokument är en beskrivning av sakområdet ”Farliga ämnen”. Rapporten är ett levande, vägledande dokument, dels för Naturvårdsverkets prioriteringar inom området och dels för projektplanering och samordning inom SMED. Rapporten omfattar fem områden: Rapporteringskrav, Sveriges PRTR, Nationell omvärldsanalys och rapporteringsbehov, Internationell verksamhet i relation till PRTR, Samordning och internationell omvärldsanalys.Den första rapporteringen till European Pollutant Release and Transfer Register (E-PRTR) gjordes 2009-06-30 och avsåg 2007 års aktivitetsuppgifter. Därefter rapporteras data till E-PRTR årligen den 31 mars. Både PRTR och E-PRTR syftar till att införa ett register över utsläpp och överföring av föroreningar, för att underlätta allmänhetens deltagande i beslutsfattandet om miljön och att bidra till att hindra och minska nedsmutsningen av miljön. I föreliggande rapport presenteras förslag till utvecklingsmöjligheter av det svenska PRTR (Utsläpp i siffror, UTIS). Omvärldsanalysen visar att det pågår ett omfattande arbete både nationellt och internationellt inom området Farliga ämnen.
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| 10. |
- Hellsten, Sofie V., et al.
(författare)
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The gene expression of the neuronal protein, SLC38A9, changes in mouse brain after in vivo starvation and high-fat diet
- 2017
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- SLC38A9 is characterized as a lysosomal component of the amino acid sensing RagulatorRAG GTPase complex, controlling the mechanistic target of rapamycin complex 1 (mTORC1). Here, immunohistochemistry was used to map SLC38A9 in mouse brain and staining was detected throughout the brain, in cortex, hypothalamus, thalamus, hippocampus, brainstem and cerebellum. More specifically, immunostaining was found in areas known to be involved in amino acid sensing and signaling pathways e.g. piriform cortex and hypothalamus. SLC38A9 immunoreactivity co-localized with both GABAergic and glutamatergic neurons, but not with astrocytes. SLC38A9 play a key role in the mTORC1 pathway, and therefore we performed in vivo starvation and high-fat diet studies, to measure gene expression alterations in specific brain tissues and in larger brain regions. Following starvation, Slc38a9 was upregulated in brainstem and cortex, and in anterior parts of the brain (Bregma 3.2 to -2.1mm). After high-fat diet, Slc38a9 was specifically upregulated in hypothalamus, while overall downregulation was noticed throughout the brain (Bregma 3.2 to -8.6mm).
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