| 1. |
- Adman, Per, et al.
(författare)
-
171 forskare: ”Vi vuxna bör också klimatprotestera”
- 2019
-
Ingår i: Dagens nyheter (DN debatt). - Stockholm. - 1101-2447.
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DN DEBATT 26/9. Vuxna bör följa uppmaningen från ungdomarna i Fridays for future-rörelsen och protestera eftersom det politiska ledarskapet är otillräckligt. Omfattande och långvariga påtryckningar från hela samhället behövs för att få de politiskt ansvariga att utöva det ledarskap som klimatkrisen kräver, skriver 171 forskare i samhällsvetenskap och humaniora.
|
|
| 2. |
- Gaccioli, F., et al.
(författare)
-
Expression and functional characterisation of System L amino acid transporters in the human term placenta
- 2015
-
Ingår i: Reproductive Biology and Endocrinology. - : Springer Science and Business Media LLC. - 1477-7827. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Background: System L transporters LAT1 (SLC7A5) and LAT2 (SLC7A8) mediate the uptake of large, neutral amino acids in the human placenta. Many System L substrates are essential amino acids, thus representing crucial nutrients for the growing fetus. Both LAT isoforms are expressed in the human placenta, but the relative contribution of LAT1 and LAT2 to placental System L transport and their subcellular localisation are not well established. Moreover, the influence of maternal body mass index (BMI) on placental System L amino acid transport is poorly understood. Therefore the aims of this study were to determine: i) the relative contribution of the LAT isoforms to System L transport activity in primary human trophoblast (PHT) cells isolated from term placenta; ii) the subcellular localisation of LAT transporters in human placenta; and iii) placental expression and activity of System L transporters in response to maternal overweight/obesity. Methods: System L mediated leucine uptake was measured in PHT cells after treatment with si-RNA targeting LAT1 and/or LAT2. The localisation of LAT isoforms was studied in isolated microvillous plasma membranes (MVM) and basal membranes (BM) by Western blot analysis. Results were confirmed by immunohistochemistry in sections of human term placenta. Expression and activity System L transporters was measured in isolated MVM from women with varying pre-pregnancy BMI. Results: Both LAT1 and LAT2 isoforms contribute to System L transport activity in primary trophoblast cells from human term placenta. LAT1 and LAT2 transporters are highly expressed in the MVM of the syncytiotrophoblast layer at term. LAT2 is also localised in the basal membrane and in endothelial cells lining the fetal capillaries. Measurements in isolated MVM vesicles indicate that System L transporter expression and activity is not influenced by maternal BMI. Conclusions: LAT1 and LAT2 are present and functional in the syncytiotrophoblast MVM, whereas LAT2 is also expressed in the BM and in the fetal capillary endothelium. In contrast to placental System A and beta amino acid transporters, MVM System L activity is unaffected by maternal overweight/obesity.
|
|
| 3. |
- Jansson, Nina, 1976, et al.
(författare)
-
Activation of Placental mTOR Signaling and Amino Acid Transporters in Obese Women Giving Birth to Large Babies.
- 2013
-
Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 98:1, s. 105-13
-
Tidskriftsartikel (refereegranskat)abstract
- Context: Babies of obese women are often large at birth, which is associated with perinatal complications and metabolic syndrome later in life. The mechanisms linking maternal obesity to fetal overgrowth are largely unknown. Objective: We tested the hypothesis that placental insulin/IGF-I and mammalian target of rapamycin (mTOR) signaling is activated and amino acid transporter activity is increased in large babies of obese women. Design and Setting: Pregnant women were recruited prospectively for collection of placental tissue at a university hospital and academic biomedical center. Patients or Other Participants: Twenty-three Swedish pregnant women with first trimester body mass index ranging from 18.5 to 44.9 kg/m(2) and with uncomplicated pregnancies participated in the study. Interventions: There were no interventions. Main Outcome Measures: We determined the phosphorylation of key signaling molecules (including Akt, IRS-1, S6K1, 4EBP-1, RPS6, and AMPK) in the placental insulin/IGF-I, AMPK, and mTOR signaling pathways. The activity and protein expression of the amino acid transporter systems A and L were measured in syncytiotrophoblast microvillous plasma membranes. Results: Birth weights (range, 3025-4235 g) were positively correlated to maternal body mass index (P < 0.05). The activity of placental insulin/IGF-I and mTOR signaling was positively correlated (P < 0.001), whereas AMPK phosphorylation was inversely (P < 0.05) correlated to birth weight. Microvillous plasma membrane system A, but not system L, activity and protein expression of the system A isoform SNAT2 were positively correlated to birth weight (P < 0.001). Conclusions: Up-regulation of specific placental amino acid transporter isoforms may contribute to fetal overgrowth in maternal obesity. This effect may be mediated by activation of insulin/IGF-I and mTOR signaling pathways, which are positive regulators of placental amino acid transporters.
|
|
| 4. |
- Lindgren, Ulrika, et al.
(författare)
-
Mitochondrial pathology in inclusion body myositis
- 2015
-
Ingår i: Neuromuscular Disorders. - : Elsevier BV. - 0960-8966. ; 25:4, s. 281-288
-
Tidskriftsartikel (refereegranskat)abstract
- Inclusion body myositis (IBM) is usually associated with a large number of cytochrome c oxidase (COX)-deficient muscle fibers and acquired mitochondrial DNA (mtDNA) deletions. We studied the number of COX-deficient fibers and the amount of mtDNA deletions, and if variants in nuclear genes involved in mtDNA maintenance may contribute to the occurrence of mtDNA deletions in IBM muscle. Twenty-six IBM patients were included. COX-deficient fibers were assayed by morphometry and mtDNA deletions by qPCR. POLG was analyzed in all patients by Sanger sequencing and C10orf2 (Twinkle), DNA2, MGME1, OPA1, POLG2, RRM2B, SLC25A4 and TYMP in six patients by next generation sequencing. Patients with many COX-deficient muscle fibers had a significantly higher proportion of mtDNA deletions than patients with few COX-deficient fibers. We found previously unreported variants in POLG and C10orf2 and IBM patients had a significantly higher frequency of an RRM2B variant than controls. POLG variants appeared more common in IBM patients with many COX-deficient fibers, but the difference was not statistically significant. We conclude that COX-deficient fibers in inclusion body myositis are associated with multiple mtDNA deletions. In IBM patients we found novel and also previously reported variants in genes of importance for mtDNA maintenance that warrants further studies. (C) 2014 Elsevier B.V. All rights reserved.
|
|
| 5. |
- Oldfors Hedberg, Carola, 1969, et al.
(författare)
-
Respiratory chain dysfunction in perifascicular muscle fibres in patients with dermatomyositis is associated with mitochondrial DNA depletion
- 2022
-
Ingår i: Neuropathology and Applied Neurobiology. - : Wiley. - 0305-1846 .- 1365-2990. ; 48:7
-
Tidskriftsartikel (refereegranskat)abstract
- Aims Patients with dermatomyositis (DM) suffer from reduced aerobic metabolism contributing to impaired muscle function, which has been linked to cytochrome c oxidase (COX) deficiency in muscle tissue. This mitochondrial respiratory chain dysfunction is typically seen in perifascicular regions, which also show the most intense inflammatory reaction along with capillary loss and muscle fibre atrophy. The objective of this study was to investigate the pathobiology of the oxidative phosphorylation deficiency in DM. Methods Muscle biopsy specimens with perifascicular COX deficiency from five juveniles and seven adults with DM were investigated. We combined immunohistochemical analyses of subunits in the respiratory chain including complex I (subunit NDUFB8), complex II (succinate dehydrogenase, subunit SDHB) and complex IV (COX, subunit MTCO1) with in situ hybridisation, next generation deep sequencing and quantitative polymerase chain reaction (PCR). Results There was a profound deficiency of complexes I and IV in the perifascicular regions with enzyme histochemical COX deficiency, whereas succinate dehydrogenase activity and complex II were preserved. In situ hybridisation of mitochondrial RNA showed depletion of mitochondrial DNA (mtDNA) transcripts in the perifascicular regions. Analysis of mtDNA by next generation deep sequencing and quantitative PCR in affected muscle regions showed an overall reduction of mtDNA copy number particularly in the perifascicular regions. Conclusion The respiratory chain dysfunction in DM muscle is associated with mtDNA depletion causing deficiency of complexes I and IV, which are partially encoded by mtDNA, whereas complex II, which is entirely encoded by nuclear DNA, is preserved. The depletion of mtDNA indicates a perturbed replication of mtDNA explaining the muscle pathology and the disturbed aerobic metabolism.
|
|
| 6. |
|
|
| 7. |
- Roos, Sara, 1979, et al.
(författare)
-
A novel mitochondrial tRNA Arg mutation resulting in an anticodon swap in a patient with mitochondrial encephalomyopathy.
- 2013
-
Ingår i: European journal of human genetics : EJHG. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 21:5, s. 571-3
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We report a mutation in the anticodon of the tRNA(Arg) gene (m.10437G>A), resulting in an anticodon swap from GCU to ACU, which is the anticodon of tRNA(Trp), in a boy with mitochondrial encephalomyopathy. Enzyme histochemical analysis of muscle tissue and biochemical analysis of isolated muscle mitochondria demonstrated cytochrome c oxidase (COX) deficiency. Restriction fragment length polymorphism analysis showed that 90% of muscle and 82% of urinary epithelium mtDNA harbored the mutation. The mutation was not identified in blood, fibroblasts, hair roots, or buccal epithelial cells and it was absent in the asymptomatic mother, suggesting that it was a de novo mutation. Single-fiber PCR analysis showed that the proportion of mutated mtDNA correlated with enzyme histochemical COX deficiency. This mutation adds to the three previously described disease-causing mutations in tRNA(Arg), but it is the first mutation occurring in the anticodon of tRNA(Arg).European Journal of Human Genetics advance online publication, 11 July 2012; doi:10.1038/ejhg.2012.153.
|
|
| 8. |
- Roos, Sara, 1979, et al.
(författare)
-
Expression of placental mammalian target of rapamycin (mTOR) is altered in relation to fetal growth and mTOR regulates leucine transport
- 2005
-
Ingår i: Placenta. - 0143-4004. ; 26:8-9
-
Konferensbidrag (refereegranskat)abstract
- Placental transport functions are altered in pregnancies complicated by restricted (IUGR) or accelerated fetal growth (LGA; large-for-gestational-age). We have suggested that the placenta may function as a nutrient sensor, regulating its nutrient transport in response to changes in substrate supply, and consequently altering fetal growth. mTOR is a protein kinase involved in regulating protein translation in response to nutrient stimuli. mTOR mRNA has been shown to be expressed in the placenta, its functional role however is unknown. To test the hypothesis that mTOR is involved in placental nutrient sensing we investigated mTOR protein expression in the human placenta in relation to fetal growth and we assessed the effect of the mTOR inhibitor rapamycin on amino acid transporter activity. Methods: mTOR expression was studied by immunohistochemistry and Western blotting and amino acid transporter activity was measured in term villous fragments. Results: mTOR protein was expressed in the cytoplasm of the syncytiotrophoblast. mTOR protein expression was up-regulated by 51% (p < 0.05) in homogenates of IUGR placentas (n = 9, controls n = 12) and down-regulated by 42% (p < 0.05) in placentas of LGA infants (n = 6, controls n = 15). Rapamycin (100 nM) decreased system L activity by 35% (n = 7, p < 0.05) but did not affect the activity of system A or taurine transporters. Conclusion: Placental mTOR protein expression is inversely related to fetal growth. Inhibition of placental mTOR decreases placental leucine transport, representing a novel regulatory mechanism for the L amino acid transporter. These findings are compatible with the hypothesis that the mTOR signaling system may play a role in placental nutrient sensing.
|
|
| 9. |
- Roos, Sara, 1979, et al.
(författare)
-
Expression pattern of mitochondrial respiratory chain enzymes in skeletal muscle of patients with mitochondrial myopathy associated with the homoplasmic m.14674T>C variant
- 2022
-
Ingår i: Brain Pathology. - : Wiley. - 1015-6305 .- 1750-3639. ; 32:4
-
Tidskriftsartikel (refereegranskat)abstract
- Two homoplasmic variants in tRNA(Glu) (m.14674T>C/G) are associated with reversible infantile respiratory chain deficiency. This study sought to further characterize the expression of the individual mitochondrial respiratory chain complexes and to describe the natural history of the disease. Seven patients from four families with mitochondrial myopathy associated with the homoplasmic m.14674T>C variant were investigated. All patients underwent skeletal muscle biopsy and mtDNA sequencing. Whole-genome sequencing was performed in one family. Western blot and immunohistochemical analyses were used to characterize the expression of the individual respiratory chain complexes. Patients presented with hypotonia and feeding difficulties within the first weeks or months of life, except for one patient who first showed symptoms at 4 years of age. Histopathological findings in muscle included lipid accumulation, numerous COX-deficient fibers, and mitochondrial proliferation. Ultrastructural abnormalities included enlarged mitochondria with concentric cristae and dense mitochondrial matrix. The m.14674T>C variant in MT-TE was identified in all patients. Immunohistochemistry and immunoblotting demonstrated pronounced deficiency of the complex I subunit NDUFB8. The expression of MTCO1, a complex IV subunit, was also decreased, but not to the same extent as NDUFB8. Longitudinal follow-up data demonstrated that not all features of the disorder are entirely transient, that the disease may be progressive, and that signs and symptoms of myopathy may develop during childhood. This study sheds new light on the involvement of complex I in reversible infantile respiratory chain deficiency, it shows that the disorder may be progressive, and that myopathy can develop without an infantile episode.
|
|
| 10. |
- Roos, Sara, 1979, et al.
(författare)
-
Histopathological changes in skeletal muscle associated with chronic ischaemia.
- 2016
-
Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 1600-0463. ; 124:11, s. 935-941
-
Tidskriftsartikel (refereegranskat)abstract
- Muscle biopsy is an essential part in the diagnostic workup in patients with suspected neuromuscular disorders. It is therefore important to be aware of morphological alterations that can be caused by systemic factors or natural ageing. Chronic limb ischaemia is frequent in elderly individuals. This study was performed to examine histopathological and mitochondrial changes in muscle in patients with chronic critical limb ischaemia. Muscle biopsy of skeletal muscle of the lower limb of patients with chronic ischaemia leading to amputation was performed and compared with muscle biopsies of healthy, age-matched controls. The histopathological abnormalities included fibrosis, necrosis, atrophy, glycogen depletion, internal nuclei, rimmed vacuoles, fibre type grouping, cytochrome c oxidase deficient fibres, MHC-I upregulation, and signs of microangiopathy. The only alteration found in age-matched controls was a few cytochrome c oxidase deficient fibres. There were also increased levels of multiple mitochondrial DNA deletions in ischaemic muscles compared with controls. Critical limb ischaemia is associated with significant histopathological changes in muscle tissue and also increased levels of mitochondrial DNA deletions. Since the alterations mimic different primary myopathic changes, chronic ischaemia is important to consider as a differential diagnosis in elderly individuals, investigated with muscle biopsy for muscle disease.
|
|
