| 1. |
- Guala, Dimitri, et al.
(författare)
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Experimental validation of predicted cancer genes using FRET
- 2018
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Ingår i: METHODS AND APPLICATIONS IN FLUORESCENCE. - : IOP PUBLISHING LTD. - 2050-6120. ; 6:3
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Tidskriftsartikel (refereegranskat)abstract
- Huge amounts of data are generated in genome wide experiments, designed to investigate diseases with complex genetic causes. Follow up of all potential leads produced by such experiments is currently cost prohibitive and time consuming. Gene prioritization tools alleviate these constraints by directing further experimental efforts towards the most promising candidate targets. Recently a gene prioritization tool called MaxLink was shown to outperform other widely used state-of-the-art prioritization tools in a large scale in silico benchmark. An experimental validation of predictions made by MaxLink has however been lacking. In this study we used Fluorescence Resonance Energy Transfer, an established experimental technique for detection of protein-protein interactions, to validate potential cancer genes predicted by MaxLink. Our results provide confidence in the use of MaxLink for selection of new targets in the battle with polygenic diseases.
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| 2. |
- Sarneel, Judith M., et al.
(författare)
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Reading tea leaves worldwide : decoupled drivers of initial litter decomposition mass-loss rate and stabilization
- 2024
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Ingår i: Ecology Letters. - : John Wiley & Sons. - 1461-023X .- 1461-0248. ; 27:5
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Tidskriftsartikel (refereegranskat)abstract
- The breakdown of plant material fuels soil functioning and biodiversity. Currently, process understanding of global decomposition patterns and the drivers of such patterns are hampered by the lack of coherent large-scale datasets. We buried 36,000 individual litterbags (tea bags) worldwide and found an overall negative correlation between initial mass-loss rates and stabilization factors of plant-derived carbon, using the Tea Bag Index (TBI). The stabilization factor quantifies the degree to which easy-to-degrade components accumulate during early-stage decomposition (e.g. by environmental limitations). However, agriculture and an interaction between moisture and temperature led to a decoupling between initial mass-loss rates and stabilization, notably in colder locations. Using TBI improved mass-loss estimates of natural litter compared to models that ignored stabilization. Ignoring the transformation of dead plant material to more recalcitrant substances during early-stage decomposition, and the environmental control of this transformation, could overestimate carbon losses during early decomposition in carbon cycle models.
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| 3. |
- Akiba, K., et al.
(författare)
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Measurement of thermal properties of the LHCb VELO detector using track-based software alignment
- 2023
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Ingår i: Journal of Instrumentation. - : Institute of Physics (IOP). - 1748-0221. ; 18:10
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Tidskriftsartikel (refereegranskat)abstract
- The thermal properties of the LHCb Vertex Locator (VELO) are studied using the real-time detector alignment procedure. The variation of the position and orientation of the detector elements as a function of the operating temperature of the VELO is presented. This study uses a dataset collected by the LHCb experiment during a VELO temperature scan performed at the end of LHC Run 2 (October 2018). Significant shrinkage of the VELO modules is observed at the operating temperature of -30(degrees)C compared to the laboratory measurements on a single module taken at a range of temperatures from +45(degrees)C to -25(degrees)C. The thermal shrinkage expected from the extrapolation of laboratory measurements to lower temperatures, and the results of this alignment study are in good agreement.
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| 4. |
- Gjelstad, I. M. F., et al.
(författare)
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Expression of perilipins in human skeletal muscle in vitro and in vivo in relation to diet, exercise and energy balance
- 2012
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Ingår i: Archives of Physiology and Biochemistry. - : Informa UK Limited. - 1381-3455 .- 1744-4160. ; 118:1, s. 22-30
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Tidskriftsartikel (refereegranskat)abstract
- The perilipin proteins enclose intracellular lipid droplets. We describe the mRNA expression of the five perilipins in human skeletal muscle in relation to fatty acid supply, exercise and energy balance. We observed that all perilipins were expressed in skeletal muscle biopsies with the highest mRNA levels of perilipin 2, 4 and 5. Cultured myotubes predominantly expressed perilipin 2 and 3. In vitro, incubation of myotubes with fatty acids enhanced mRNA expression of perilipin 1, 2 and 4. In vivo, low fat diet increased mRNA levels of perilipin 3 and 4. Endurance training, but not strength training, enhanced the expression of perilipin 2 and 3. Perilipin 1 mRNA correlated positively with body fat mass, whereas none of the perilipins were associated with insulin sensitivity. In conclusion, all perilipins mRNAs were expressed in human skeletal muscle. Diet as well as endurance exercise modulated the expression of perilipins.
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| 5. |
- Hemke, Robert, et al.
(författare)
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Imaging assessment of children presenting with suspected or known juvenile idiopathic arthritis : ESSR-ESPR points to consider.
- 2020
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Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 30:10, s. 5237-5249
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Tidskriftsartikel (refereegranskat)abstract
- Juvenile idiopathic arthritis (JIA) is the most common paediatric rheumatic disease. It represents a group of heterogenous inflammatory disorders with unknown origin and is a diagnosis of exclusion in which imaging plays an important role. JIA is defined as arthritis of one or more joints that begins before the age of 16 years, persists for more than 6 weeks and is of unknown aetiology and pathophysiology. The clinical goal is early suppression of inflammation to prevent irreversible joint damage which has shifted the emphasis from detecting established joint damage to proactively detecting inflammatory change. This drives the need for imaging techniques that are more sensitive than conventional radiography in the evaluation of inflammatory processes as well as early osteochondral change. Physical examination has limited reliability, even if performed by an experienced clinician, emphasising the importance of imaging to aid in clinical decision-making. On behalf of the European Society of Musculoskeletal Radiology (ESSR) arthritis subcommittee and the European Society of Paediatric Radiology (ESPR) musculoskeletal imaging taskforce, based on literature review and/or expert opinion, we discuss paediatric-specific imaging characteristics of the most commonly involved, in literature best documented and clinically important joints in JIA, namely the temporomandibular joints (TMJs), spine, sacroiliac (SI) joints, wrists, hips and knees, followed by a clinically applicable point to consider for each joint. We will also touch upon controversies in the current literature that remain to be resolved with ongoing research. KEY POINTS: • Juvenile idiopathic arthritis (JIA) is the most common chronic paediatric rheumatic disease and, in JIA imaging, is increasingly important to aid in clinical decision-making. • Conventional radiographs have a lower sensitivity and specificity for detection of disease activity and early destructive change, as compared to MRI or ultrasound. Nonetheless, radiography remains important, particularly in narrowing the differential diagnosis and evaluating growth disturbances. • Mainly in peripheral joints, ultrasound can be helpful for assessment of inflammation and guiding joint injections. In JIA, MRI is the most validated technique. MRI should be considered as the modality of choice to assess the axial skeleton or where the clinical presentation overlaps with JIA.
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| 6. |
- Jans, A., et al.
(författare)
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Impact of dietary fat quantity and quality on skeletal muscle fatty acid metabolism in subjects with the metabolic syndrome
- 2012
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Ingår i: Metabolism. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 61:11, s. 1554-1565
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Tidskriftsartikel (refereegranskat)abstract
- Insulin resistance is characterized by disturbances in lipid metabolism in skeletal muscle. Our aim was to investigate whether gene expression and fatty acid (FA) profile of skeletal muscle lipids are affected by diets differing in fat quantity and quality in subjects with the metabolic syndrome (MetS) and varying degrees of insulin sensitivity. 84 subjects (age 57.3 ± 0.9 y, BMI 30.9 ± 0.4 kg/m 2, 42 M/42 F) were randomly assigned to one of four iso-energetic diets: high-SFA (HSFA); high-MUFA (HMUFA) or two low-fat, high-complex carbohydrate diets, supplemented with 1.24 g/day of long-chain n-3 PUFA (LFHCCn-3) or control oil (LFHCC) for 12 weeks. In a subgroup of men (n = 26), muscle TAG, DAG, FFA and phospholipid contents were determined including their fractional synthetic rate (FSR) and FA composition at fasting and 4 h after consumption of a high-fat mixed-meal, both pre- and post-intervention. Genes involved in lipogenesis were downregulated after HMUFA (mean fold change - 1.3) and after LFHCCn-3 (fold change - 1.7) in insulin resistant subjects (< median of (S I)), whereas in insulin sensitive subjects (> median of insulin sensitivity) the opposite effect was shown (fold change + 1.6 for both diets). HMUFA diet tended to decrease FSR in TAG (P =.055) and DAG (P =.066), whereas the LFHCCn-3 diet reduced TAG content (P =.032). In conclusion, HMUFA and LFHCCn-3 diets reduced the expression of the lipogenic genes in skeletal muscle of insulin resistant subjects, whilst HMUFA reduced the fractional synthesis rate of DAG and TAG and LFHCC n-3 the TAG content. Our data indicate that these diets may reduce muscle fat accumulation by affecting the balance between FA synthesis, storage and oxidation.
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| 7. |
- Moro, Elena, et al.
(författare)
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Long-Term Results of a Multicenter Study on Subthalamic and Pallidal Stimulation in Parkinson's Disease
- 2010
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 25:5, s. 578-586
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Tidskriftsartikel (refereegranskat)abstract
- We report the 5 to 6 year follow-up of a multicenter study of bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) in advanced Parkinson's disease (PD) patients. Thirty-live STN patients and 16 GPi patienis were assessed at 5 to 6 years after DBS surgery. Primary outcome measure was the stimulation effect on the motor Unified Parkinson's Disease Rating Scale (UPDRS) assessed with a prospective cross-over double-blind assessment without medications (stimulation was randomly switched on or off). Secondary outcomes were motor UPDRS changes with unblinded assessments in off- and on-medication states with and without stimulation, activities of daily living (ADL), anti-PD medications, and dyskinesias. In double-blind assessment, both STN and GPi DBS were significantly effective in improving the motor UPDRS scores (STN. P < 0.0001, 45.4%; GPi, P = 0.008, 20.0%) compared with of regardless of the sequence of stimulation. In open assessment. both STN- and GPi-DBS significantly improved the off-medication motor UPDRS when compared with before surgery (STN. P < 0.001, 50.5%; GPi, P = 0.002, 35.6%). Dyskinesias and ADL were significantly improved in both groups. Anti-PD medications were significantly reduced only in the STN group. Adverse events were more frequent in the STN group. These results confirm the long-term efficacy of STN and GPi DBS advanced PD. Although the surgical targets were not randomized, there was a trend to 1 better outcome of motor signs in the STN-DBS patients and fewer adverse events in the GPi-DBS group. (C) 2010 Movement Disorder Society
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| 8. |
- Pekkinen, M., et al.
(författare)
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Osteoporosis and skeletal dysplasia caused by pathogenic variants in SGMS2
- 2019
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Ingår i: Jci Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 4:7
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Tidskriftsartikel (refereegranskat)abstract
- Mechanisms leading to osteoporosis are incompletely understood. Genetic disorders with skeletal fragility provide insight into metabolic pathways contributing to bone strength. We evaluated 6 families with rare skeletal phenotypes and osteoporosis by next-generation sequencing. In all the families, we identified a heterozygous variant in SGMS2, a gene prominently expressed in cortical bone and encoding the plasma membrane-resident sphingomyelin synthase SMS2. Four unrelated families shared the same nonsense variant, c.148C>T (p.Arg50*), whereas the other families had a missense variant, c.185T>G (p.IIe62Ser) or c.191T>G (p.Met64Arg). Subjects with p.Arg50* presented with childhood-onset osteoporosis with or without cranial sclerosis. Patients with p.IIe62Ser or p.Met64Arg had a more severe presentation, with neonatal fractures, severe short stature, and spondylometaphyseal dysplasial Several subjects had experienced peripheral facial nerve palsy or other neurological manifestations. Bone biopsies showed markedly altered bone material characteristics, including defective bone mineralization. Osteoclast formation and function in vitro was normal. While the p.Arg50* mutation yielded a catalytically inactive enzyme, p.IIe62Ser and p.Met64Arg each enhanced the rate of de novo sphingomyelin production by blocking export of a functional enzyme from the endoplasmic reticulum. SGMS2 pathogenic variants underlie a spectrum of skeletal conditions, ranging from isolated osteoporosis to complex skeletal dysplasia, suggesting a critical role for plasma membrane-bound sphingomyelin metabolism in skeletal homeostasis.
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| 9. |
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| 10. |
- Vasudevan, S G, et al.
(författare)
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Characterisation of inter- and intra-molecular interactions of the dengue virus RNA dependent RNA polymerase as potential drug targets
- 2001
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Ingår i: Il Farmaco. - : Elsevier BV. - 0014-827X .- 1879-0569. ; 56:1-2, s. 33-36
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Tidskriftsartikel (refereegranskat)abstract
- Our research is directed towards enhancing the understanding of the molecular biology of dengue virus replication with the ultimate goal being to develop novel antiviral strategies based on preventing critical inter- or intra-molecular interactions required for the normal virus life cycle. The viral RNA-dependent RNA polymerase (NS5) and the viral helicase (NS3) interaction offers a possible target for inhibitors to bind and prevent replication. In this study the yeast-two hybrid system was used to show that a small region of NS5 interacts with NS3, and also with the cellular nuclear transport receptor importin-beta. Furthermore, intramolecular interaction between the two putative domains of NS5 can also be detected by the yeast two-hybrid assay. We have also modified the colony lift assay for the beta-galactosidase reporter activity in intact yeast cells which reflects the strength of interaction between two proteins to a microtiter plate format. This assay offers a unique opportunity to screen for small molecule compounds that block physiologically important interactions.
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