| 1. |
- Bajusz, Csaba, et al.
(författare)
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The nuclear activity of the actin-binding Moesin protein is necessary for gene expression in Drosophila
- 2021
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Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 288:16, s. 4812-4832
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Tidskriftsartikel (refereegranskat)abstract
- Ezrin-Radixin-Moesin (ERM) proteins play an essential role in the cytoplasm by cross-linking actin filaments with plasma membrane proteins. Research has identified the nuclear localization of ERMs, as well as the involvement of a single Drosophila ERM protein, Moesin, in nuclear mRNA exports. However, the question of how important the nuclear activity of ERM proteins are for the life of an organism has so far not been explored. Here, we present the first attempt to reveal the in vivo relevance of nuclear localization of Moesin in Drosophila. With the help of a nuclear export signal, we decreased the amount of Moesin in the nuclei of the animals. Furthermore, we observed various developmental defects, demonstrating the importance of ERM function in the nucleus for the first time. Transcriptome analysis of the mutant flies revealed that the lack of nuclear Moesin function leads to expression changes in nearly 700 genes, among them heat-shock genes. This result together with additional findings revealed that in Drosophila the expression of protein chaperones requires the nuclear functions of Moesin.
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| 2. |
- George, Julie, et al.
(författare)
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Comprehensive genomic profiles of small cell lung cancer
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 524:7563, s. 47-U73
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Tidskriftsartikel (refereegranskat)abstract
- We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.
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| 3. |
- van Setten, Jessica, et al.
(författare)
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PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
- 2018
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genomewide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are overrepresented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of similar to 105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ionchannel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.
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| 4. |
- Björkman, Anne, 1981, et al.
(författare)
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Tundra Trait Team: A database of plant traits spanning the tundra biome
- 2018
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Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 27:12, s. 1402-1411
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Tidskriftsartikel (refereegranskat)abstract
- © 2018 The Authors Global Ecology and Biogeography Published by John Wiley & Sons Ltd Motivation: The Tundra Trait Team (TTT) database includes field-based measurements of key traits related to plant form and function at multiple sites across the tundra biome. This dataset can be used to address theoretical questions about plant strategy and trade-offs, trait–environment relationships and environmental filtering, and trait variation across spatial scales, to validate satellite data, and to inform Earth system model parameters. Main types of variable contained: The database contains 91,970 measurements of 18 plant traits. The most frequently measured traits (>1,000 observations each) include plant height, leaf area, specific leaf area, leaf fresh and dry mass, leaf dry matter content, leaf nitrogen, carbon and phosphorus content, leaf C:N and N:P, seed mass, and stem specific density. Spatial location and grain: Measurements were collected in tundra habitats in both the Northern and Southern Hemispheres, including Arctic sites in Alaska, Canada, Greenland, Fennoscandia and Siberia, alpine sites in the European Alps, Colorado Rockies, Caucasus, Ural Mountains, Pyrenees, Australian Alps, and Central Otago Mountains (New Zealand), and sub-Antarctic Marion Island. More than 99% of observations are georeferenced. Time period and grain: All data were collected between 1964 and 2018. A small number of sites have repeated trait measurements at two or more time periods. Major taxa and level of measurement: Trait measurements were made on 978 terrestrial vascular plant species growing in tundra habitats. Most observations are on individuals (86%), while the remainder represent plot or site means or maximums per species. Software format: csv file and GitHub repository with data cleaning scripts in R; contribution to TRY plant trait database (www.try-db.org) to be included in the next version release.
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| 5. |
- Casanueva, Felipe F., et al.
(författare)
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Criteria for the definition of Pituitary Tumor Centers of Excellence (PTCOE): A Pituitary Society Statement
- 2017
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Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403. ; 20, s. 489-498
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Forskningsöversikt (refereegranskat)abstract
- © 2017, The Author(s). Introduction: With the goal of generate uniform criteria among centers dealing with pituitary tumors and to enhance patient care, the Pituitary Society decided to generate criteria for developing Pituitary Tumors Centers of Excellence (PTCOE). Methods: To develop that task, a group of ten experts served as a Task Force and through two years of iterative work an initial draft was elaborated. This draft was discussed, modified and finally approved by the Board of Directors of the Pituitary Society. Such document was presented and debated at a specific session of the Congress of the Pituitary Society, Orlando 2017, and suggestions were incorporated. Finally the document was distributed to a large group of global experts that introduced further modifications with final endorsement. Results: After five years of iterative work a document with the ideal criteria for a PTCOE is presented. Conclusions: Acknowledging that very few centers in the world, if any, likely fulfill the requirements here presented, the document may be a tool to guide improvements of care delivery to patients with pituitary disorders. All these criteria must be accommodated to the regulations and organization of Health of a given country.
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| 6. |
- Gáll, Tamás, et al.
(författare)
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Heme induces endoplasmic reticulum stress (Hier stress) in human aortic smooth muscle cells
- 2018
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9:NOV
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Tidskriftsartikel (refereegranskat)abstract
- Accumulation of damaged or misfolded proteins resulted from oxidative protein modification induces endoplasmic reticulum (ER) stress by activating the pathways of unfolded protein response. In pathologic hemolytic conditions, extracellular free hemoglobin is submitted to rapid oxidation causing heme release. Resident cells of atherosclerotic lesions, after intraplaque hemorrhage, are exposed to heme leading to oxidative injury. Therefore, we raised the question whether heme can also provoke ER stress. Smooth muscle cells are one of the key players of atherogenesis; thus, human aortic smooth muscle cells (HAoSMCs) were selected as a model cell to reveal the possible link between heme and ER stress. Using immunoblotting, quantitative polymerase chain reaction and immunocytochemistry, we quantitated the markers of ER stress. These were: phosphorylated eIF2α, Activating transcription factor-4 (ATF4), DNA-damage-inducible transcript 3 (also known as C/EBP homology protein, termed CHOP), X-box binding protein-1 (XBP1), Activating transcription factor-6 (ATF6), GRP78 (glucose-regulated protein, 78kDa) and heme responsive genes heme oxygenase-1 and ferritin. In addition, immunohistochemistry was performed on human carotid artery specimens from patients who had undergone carotid endarterectomy. We demonstrate that heme increases the phosphorylation of eiF2α in HAoSMCs and the expression of ATF4. Heme also enhances the splicing of XBP1 and the proteolytic cleavage of ATF6. Consequently, there is up-regulation of target genes increasing both mRNA and protein levels of CHOP and GRP78. However, TGFβ and collagen type I decreased. When the heme binding proteins, alpha-1-microglobulin (A1M) and hemopexin (Hpx) are present in cell media, the ER stress provoked by heme is inhibited. ER stress pathways are also retarded by the antioxidant N-acetyl cysteine (NAC) indicating that reactive oxygen species are involved in heme-induced ER stress. Consistent with these findings, elevated expression of the ER stress marker GRP78 and CHOP were observed in smooth muscle cells of complicated lesions with hemorrhage compared to either atheromas or healthy arteries. In conclusion, heme triggers ER stress in a time- and dose-dependent manner in HAoSMCs. A1M and Hpx as well as NAC effectively hamper heme-induced ER stress, supporting their use as a potential therapeutic approach to reverse such a deleterious effects of heme toxicity.
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| 7. |
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| 8. |
- Péter, Annamária, et al.
(författare)
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Comparing Surface and Fine-Wire Electromyography Activity of Lower Leg Muscles at Different Walking Speeds.
- 2019
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Ingår i: Frontiers in Physiology. - : Frontiers Media S.A.. - 1664-042X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Ankle plantar flexor muscles are active in the stance phase of walking to propel the body forward. Increasing walking speed requires increased plantar flexor excitation, frequently assessed using surface electromyography (EMG). Despite its popularity, validity of surface EMG applied on shank muscles is mostly unclear. Thus, we examined the agreement between surface and intramuscular EMG at a range of walking speeds. Ten participants walked overground at slow, preferred, fast, and maximum walking speeds (1.01 ± 0.13, 1.43 ± 0.19, 1.84 ± 0.23, and 2.20 ± 0.38 m s-1, respectively) while surface and fine-wire EMG activities of flexor hallucis longus (FHL), soleus (SOL), medial gastrocnemius (MG) and lateral gastrocnemius (LG), and tibialis anterior (TA) muscles were recorded. Surface and intramuscular peak-normalised EMG amplitudes were compared for each muscle and speed across the stance phase using Statistical Parametric Mapping. In FHL, we found differences around peak activity at all speeds except fast. There was no difference in MG at any speed or in LG at slow and preferred speeds. For SOL and LG, differences were seen in the push-off phase at fast and maximum walking speeds. In SOL and TA, surface EMG registered activity during phases in which intramuscular EMG indicated inactivity. Our results suggest that surface EMG is generally a suitable method to measure MG and LG EMG activity across several walking speeds. Minimising cross-talk in FHL remains challenging. Furthermore, SOL and TA muscle onset/offset defined by surface EMG should be interpreted cautiously. These findings should be considered when recording and interpreting surface EMG of shank muscles in walking.
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| 9. |
- Péter, Annamária, et al.
(författare)
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Effect of footwear on intramuscular EMG activity of plantar flexor muscles in walking.
- 2020
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Ingår i: Journal of Electromyography & Kinesiology. - : Elsevier. - 1050-6411 .- 1873-5711. ; 55
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Tidskriftsartikel (refereegranskat)abstract
- One of the purposes of footwear is to assist locomotion, but some footwear types seem to restrict natural foot motion, which may affect the contribution of ankle plantar flexor muscles to propulsion. This study examined the effects of different footwear conditions on the activity of ankle plantar flexors during walking. Ten healthy habitually shod individuals walked overground in shoes, barefoot and in flip-flops while fine-wire electromyography (EMG) activity was recorded from flexor hallucis longus (FHL), soleus (SOL), and medial and lateral gastrocnemius (MG and LG) muscles. EMG signals were peak-normalised and analysed in the stance phase using Statistical Parametric Mapping (SPM). We found highly individual EMG patterns. Although walking with shoes required higher muscle activity for propulsion than walking barefoot or with flip-flops in most participants, this did not result in statistically significant differences in EMG amplitude between footwear conditions in any muscle (p > 0.05). Time to peak activity showed the lowest coefficient of variation in shod walking (3.5, 7.0, 8.0 and 3.4 for FHL, SOL, MG and LG, respectively). Future studies should clarify the sources and consequences of individual EMG responses to different footwear.
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| 10. |
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