| 1. |
- Ramilowski, JA, et al.
(författare)
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Functional annotation of human long noncoding RNAs via molecular phenotyping
- 2020
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Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 30:7, s. 1060-1072
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Tidskriftsartikel (refereegranskat)abstract
- Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-to-date lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2.
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| 2. |
- Forrest, ARR, et al.
(författare)
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A promoter-level mammalian expression atlas
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 507:7493, s. 462-
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Tidskriftsartikel (refereegranskat)
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| 10. |
- Skogar, O, et al.
(författare)
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"Effects of Tactile Touch on pain, sleep and health related quality of life in Parkinsons disease with chronic pain": A randomized, controlled and prospective study
- 2013
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Ingår i: European Journal of Integrative Medicine. - : Elsevier. - 1876-3820 .- 1876-3839. ; 5:2, s. 141-152
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Parkinsons disease (PD) is often associated with chronic PD related pain. Complementary medicine are widely used but randomized, controlled and prospective studies of the effects are sparse. less thanbrgreater than less thanbrgreater thanAims of the study: To compare the effects of Tactile Touch (TT) with Rest to Music (RTM) in PD patients with chronic pain and to describe effects within groups. less thanbrgreater than less thanbrgreater thanPatients and methods: A 34 week controlled randomized and prospective trial compared the effects of TT with RTM in 45 (29 TT and 16 RTM) patients with PD and chronic pain. The whole body tactile stimulation method was performed for each individual patient by the same therapist for 10 times during the first 8 weeks. The RTM group received the same therapy except for the tactile stimulation. Pharmacotherapy was kept unchanged. Participants were assessed at pre- and post-intervention for pain, sleep patterns and health related quality of life (HRQoL). less thanbrgreater than less thanbrgreater thanResults: Differences between TT and RTM groups were few. Total PDSS significantly improved within the TT but not in the RTM-group. No significant differences between groups were seen in pain parameters, although significant improvements were seen within the TT-group after the intervention period. There were significant improvements within both groups in HRQoL and between groups in the items physical role and social functioning 4 weeks after screening. less thanbrgreater than less thanbrgreater thanConclusions: No significant differences between the TT and RTM groups were seen. Only in single aspects did patients with PD and chronic pain have more benefit more from CAM therapy with TT in combination with RTM.
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| 14. |
- Chitu, V., et al.
(författare)
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The PDGFR Receptor Family
- 2015
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Ingår i: Receptor Tyrosine Kinases: Family and Subfamilies. - Cham : Springer International Publishing. - 9783319118871 - 9783319118888 ; , s. 373-538
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Bokkapitel (refereegranskat)
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| 15. |
- Claesson, A., et al.
(författare)
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Unmanned aerial vehicles (drones) in out-of-hospital-cardiac-arrest
- 2016
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Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : BioMed Central (BMC). - 1757-7241. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of an automated external defibrillator (AED) prior to EMS arrival can increase 30-day survival in out-of-hospital cardiac arrest (OHCA) significantly. Drones or unmanned aerial vehicles (UAV) can fly with high velocity and potentially transport devices such as AEDs to the site of OHCAs. The aim of this explorative study was to investigate the feasibility of a drone system in decreasing response time and delivering an AED. Methods: Data of Global Positioning System (GPS) coordinates from historical OHCA in Stockholm County was used in a model using a Geographic Information System (GIS) to find suitable placements and visualize response times for the use of an AED equipped drone. Two different geographical models, urban and rural, were calculated using a multi-criteria evaluation (MCE) model. Test-flights with an AED were performed on these locations in rural areas. Results: In total, based on 3,165 retrospective OHCAs in Stockholm County between 2006-2013, twenty locations were identified for the potential placement of a drone. In a GIS-simulated model of urban OHCA, the drone arrived before EMS in 32 % of cases, and the mean amount of time saved was 1.5 min. In rural OHCA the drone arrived before EMS in 93 % of cases with a mean amount of time saved of 19 min. In these rural locations during (n = 13) test flights, latch-release of the AED from low altitude (3-4 m) or landing the drone on flat ground were the safest ways to deliver an AED to the bystander and were superior to parachute release. Discussion: The difference in response time for EMS between urban and rural areas is substantial, as is the possible amount of time saved using this UAV-system. However, yet another technical device needs to fit into the chain of survival. We know nothing of how productive or even counterproductive this system might be in clinical reality. Conclusions: To use drones in rural areas to deliver an AED in OHCA may be safe and feasible. Suitable placement of drone systems can be designed by using GIS models. The use of an AED equipped drone may have the potential to reduce time to defibrillation in OHCA.
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| 16. |
- Crumley, Carole L., et al.
(författare)
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Is There a Future for the Past?
- 2018
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Ingår i: Issues and Concepts in Historical Ecology. - : Cambridge University Press. - 9781108420983 - 9781108355780 ; , s. 1-9
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Konferensbidrag (refereegranskat)
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| 19. |
- Jacobson, L., et al.
(författare)
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Mechanisms compensating for visual field restriction in adolescents with damage to the retro-geniculate visual system
- 2012
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Ingår i: Eye (London. 1987). - : Springer Science and Business Media LLC. - 0950-222X .- 1476-5454. ; 26:11, s. 1437-1445
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Tidskriftsartikel (refereegranskat)abstract
- Background To describe visual field (VF) outcome in three adolescents with damage to the optic radiation and to focus on mechanisms that may compensate the practical functional limitations of VF defects. Design Descriptive, prospective multi-case study in a hospital setting. Participants Three teenagers with cerebral visual dysfunction because of damage to the retro-geniculate visual pathways. Methods Best-corrected visual acuity and eye alignment were assessed. Visual field function was tested with Goldmann perimetry, and with Rarebit, Humphrey Visual Field Analyzer and Esterman computerized techniques. Fixation was registered with video oculography during Rarebit examination. Magnetic resonance imaging of the brain illustrated brain damage and its relation to the posterior visual system. Results One of the three subjects had bilateral asymmetric white matter damage of immaturity, early-onset exotropia, and a relative homonymous VF defect, but normal binocular VF. The second subject also had bilateral asymmetric white matter damage of immaturity and showed an inferior right quadrantanopia, confirmed by the binocular field. Registration of fixation revealed automatic scanning during perimetry. The third subject had an almost total left homonymous hemianopia after resection of a brain tumour in the right temporal lobe. The hemianopia could be compensated for by fast voluntary scanning. Conclusion Congenital and later-acquired homonymous VF defects may, at least in young subjects, be compensated for by scanning. Exotropia may compensate VF defects and, therefore, the VF should be tested before strabismus surgery. Eye (2012) 26, 1437-1445; doi:10.1038/eye.2012.190; published online 21 September 2012
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| 21. |
- Lennartsson, Anna-Karin, et al.
(författare)
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Perceived stress at work is associated with attenuated DHEA-S response during acute psychosocial stress
- 2013
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 38:9, s. 1650-1657
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) have been suggested to play a protective role during acute psychosocial stress, because they act as antagonists to the effects of the stress hormone cortisol. This study aims to investigate whether prolonged psychosocial stress, measured as perceived stress at work during the past week, is related to the capacity to produce DHEA and DHEA-S during acute psychosocial stress. It also aims to investigate whether prolonged perceived stress affects the balance between production of cortisol and DHEA-S during acute psychosocial stress. Method: Thirty-six healthy subjects (19 men and 17 women, mean age 37 years, SD 5 years), were included. Perceived stress at work during the past week was measured by using the Stress-Energy (SE) Questionnaire. The participants were divided into three groups based on their mean scores; Low stress, Medium stress and High stress. The participants underwent the Trier Social Stress Test (TSST) and blood samples were collected before, directly after the stress test, and after 30 min of recovery. General Linear Models were used to investigate if the Medium stress group and the High stress group differ regarding stress response compared to the Low stress group. Results: Higher perceived stress at work was associated with attenuated DHEA-S response during acute psychosocial stress. Furthermore, the ratio between the cortisol production and the DHEA-S production during the acute stress test were higher in individuals reporting higher perceived stress at work compared to individuals reporting low perceived stress at work. There was no statistical difference in DHEA response between the groups. Conclusions: This study shows that prolonged stress, measured as perceived stress at work during the past week, seems to negatively affect the capacity to produce DHEA-S during acute stress. Given the protective functions of DHEA-S, attenuated DHEA-S production during acute stress may Lead to higher risk for adverse effects on psychological and physiological health, particularly if stress exposure continues. (C) 2013 Elsevier Ltd. All rights reserved.
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| 22. |
- Lennartsson, Anna-Karin, et al.
(författare)
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Perceived Stress at Work Is Associated with Lower Levels of DHEA-S
- 2013
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is known that long-term psychosocial stress may cause or contribute to different diseases and symptoms and accelerate aging. One of the consequences of prolonged psychosocial stress may be a negative effect on the levels of dehydroepiandrosterone (DHEA) and its sulphated metabolite dehydroepiandrosterone sulphate (DHEA-S). The aim of this study is to investigate whether levels of DHEA and DHEA-S differ in individuals who report perceived stress at work compared to individuals who report no perceived stress at work. Methods: Morning fasting DHEA-S and DHEA levels were measured in serum in a non-stressed group (n = 40) and a stressed group (n = 41). DHEA and DHEA-S levels were compared between the groups using ANCOVA, controlling for age. Results: The mean DHEA-S levels were 23% lower in the subjects who reported stress at work compared to the non-stressed group. Statistical analysis (ANCOVA) showed a significant difference in DHEA-S levels between the groups (p = 0.010). There was no difference in DHEA level between the groups. Conclusions: This study indicates that stressed individual have markedly lower levels of DHEA-S. Given the important and beneficial functions of DHEA and DHEA-S, lower levels of DHEA-S may constitute one link between psychosocial stress, ill health and accelerated ageing.
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| 26. |
- Lennartsson, Tommy, et al.
(författare)
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Diversity in Ecological and Social Contexts
- 2018
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Ingår i: Issues and Concepts in Historical Ecology. - Cambridge : Cambridge University Press. - 9781108420983 - 9781108355780 ; , s. 182-239
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Konferensbidrag (refereegranskat)
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| 33. |
- Nilsson, S, et al.
(författare)
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Efficacy of a novel cytotoxic polybisphosphonate for treatment of bone metastasis in castration-resistant prostate cancer (CRPC).
- 2015
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Ingår i: JOURNAL OF CLINICAL ONCOLOGY. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 33:7
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- 236 Background: A cytostatic polybisphosphonate was developed for Tx of mCRPC. It has a) anti-resorptive effects, osteoclast inhib., b) tum. cell spec./tox, confirmed in in-vivo models. Tox. study shows high tolerability. Animal PK study has shown T½ < 3 hrs; principal accumulation in liver, spleen, kidneys. Methods: Clin phase I/IIa (clinicaltrials.gov NCT01595087): Prim obj: to define MTD of ODX given every 3rd week. Sec. obj: OS, bone metab. and resp. markers, PSA, QoL and PK. Explorative in vitrostudies (basis for rand. phase IIb trial in pts. with docetax-res. mCRPC). A docetax-resist. cell-line was developed from DU145 in escalating conc. of docetax, then continuous growth in docetax 500 µg/ml. Cells subj. to cytotox. exp. with ODX (iCELLigence system and fluorom microculture cytotox assay). Results: Clin Phase I/IIa first-in-man trial (clinicaltrials.gov NCT01595087): 17/28 patients rec. 4-7 doses every 3rd week. No DLTs; max dose adm.: 3.0 mg/kg: no drug-related SAEs. Tx was well tolerated. Efficacy and QoL data w. considerable variability as to be expected in this population of pts. w. mCRPC. Max blood conc. ODX: 110-160 fmol/mL; 85-90 % cleared within first 1 hr. Efficacy of ODX in docetax-res DU145TR: A dose-dependent cytotox effect seen when adding ODX in “sub-clin.” doses. All cells were apparently killed in the clin. relevant dose 6 uM. Conclusions: ODX is a novel drug cand. w. high cytotox. efficacy in vivo and in vitro, even in highly docetax-res. cells. Animal studies and Phase I trial show excellent tolerability. Studies now ongoing to elucidate whether short-term treatment is as efficacious as continuous treatment and whether some cells de facto may develop resistance also to this new treatment concept. A multicenter rand. double-blind pbo. controlled trial (EudraCT 2014-002054-39) starts Q4 2014 in mCRPC pts failing docetax and/or cabazitaxel AND abiraterone and/or enzalutamide. Clinical trial information: NCT01595087.
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| 34. |
- Noguchi, S, et al.
(författare)
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FANTOM5 CAGE profiles of human and mouse samples
- 2017
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Ingår i: Scientific data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4, s. 170112-
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Tidskriftsartikel (refereegranskat)abstract
- In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.
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| 36. |
- Padilla, Nelly, et al.
(författare)
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Breakdown of Whole-brain Dynamics in Preterm-born Children
- 2020
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 30:3, s. 1159-1170
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Tidskriftsartikel (refereegranskat)abstract
- The brain operates at a critical point that is balanced between order and disorder. Even during rest, unstable periods of random behavior are interspersed with stable periods of balanced activity patterns that support optimal information processing. Being born preterm may cause deviations from this normal pattern of development. We compared 33 extremely preterm (EPT) children born at < 27 weeks of gestation and 28 full-term controls. Two approaches were adopted in both groups, when they were 10 years of age, using structural and functional brain magnetic resonance imaging data. The first was using a novel intrinsic ignition analysis to study the ability of the areas of the brain to propagate neural activity. The second was a whole-brain Hopf model, to define the level of stability, desynchronization, or criticality of the brain. EPT-born children exhibited fewer intrinsic ignition events than controls; nodes were related to less sophisticated aspects of cognitive control, and there was a different hierarchy pattern in the propagation of information and suboptimal synchronicity and criticality. The largest differences were found in brain nodes belonging to the rich-club architecture. These results provide important insights into the neural substrates underlying brain reorganization and neurodevelopmental impairments related to prematurity.
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| 37. |
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| 38. |
- Sinclair, Paul, 1949-, et al.
(författare)
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Historical Ecology and the Longue Durée
- 2018
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Ingår i: Issues and Concepts in Historical Ecology. - Cambridge : Cambridge University Press. - 9781108420983 - 9781108355780 ; , s. 13-40
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Konferensbidrag (refereegranskat)
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| 39. |
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| 42. |
- Theorell, Töres, et al.
(författare)
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Self-reported psychological demands, skill discretion and decision authority at work : A twin study
- 2016
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Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 44:4, s. 354-360
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To examine the contribution of genetic factors to self-reported psychological demands (PD), skill discretion (SD) and decision authority (DA) and the possible importance of such influence on the association between these work variables and depressive symptoms.METHODS: 11,543 participants aged 27-54 in the Swedish Twin Registry participated in a web survey. First of all, in multiple regressions, phenotypic associations between each one of the three work environment variables and depressive symptoms were analysed. Secondly, by means of classical twin analysis, the genetic contribution to PD, SD and DA was assessed. After this, cross-twin cross-trait correlations were computed between PD, SD and DA, on the one hand, and depressive symptom score, on the other hand.RESULTS: The genetic contribution to self-reported PD, DS and DA ranged from 18% for decision authority to 30% for skill discretion. Cross-twin cross-trait correlations were very weak (r values < .1) and non-significant for dizygotic twins, and we lacked power to analyse the genetic architecture of the phenotypic associations using bivariate twin modelling. However, substantial genetic contribution to these associations seems unlikely.CONCLUSIONS: Genetic contributions to the self-reported work environment scores were 18-30%.
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| 43. |
- Ullen, A., et al.
(författare)
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Additive/synergistic antitumoral effects on prostate cancer cells in vitro following treatment with a combination of docetaxel and zoledronic acid
- 2005
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Ingår i: Acta Oncol. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:6, s. 644-50
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Tidskriftsartikel (refereegranskat)abstract
- Once bone metastasized and androgen independent, prostate cancer is often associated with skeletal morbidity and disability. New treatment modalities that can palliate symptoms from the skeleton and inhibit further progression are warranted. In this study, the antitumoral effects following treatment with a combination of docetaxel and the new generation bisphosphonate, zoledronic acid, were investigated on two hormone-refractory prostate cancer cell lines: PC3 and DU145. The prostate cancer cells were treated with increasing concentrations of zoledronic acid in the absence or presence of docetaxel. Toxicity was measured using fluorometric microculture cytotoxic assay technique. A concentration of 25 microM, zoledronic acid reduced the viable cell number to 68% and 98% for PC3 and DU145 cells respectively. Docetaxel, on the other hand, at a concentration of 0.1 ng/ml, had no effect on the viability. However, a combination of zoledronic acid and docetaxel reduced the cell number to 60% and 81% respectively. Furthermore, zoledronic acid in the concentration range 12.5 microM-50 microM enhanced the antitumoral effects of docetaxel (0.01-1 ng/ml) in an additive and/or synergistic manner for both cell lines. These data support the hypothesis that zoledronic acid, in addition to having bone resorption inhibiting properties, also exhibits anti-tumoral effects. It also appears that combined treatment with docetaxel causes additive and/or synergistic cytostatic effects on prostate cancer cells.
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| 44. |
- Ullen, A., et al.
(författare)
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Prostate cancer cell lines lack amplification: overexpression of HER2
- 2005
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Ingår i: Acta Oncol. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:5, s. 490-5
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Tidskriftsartikel (refereegranskat)abstract
- The potential overexpression of HER2 in prostate cancer cells has attended significant interest during the past few years, both as potential target for HER2 pathway focused therapy and as a mechanism involved in the progression to androgen independence. Conflicting results have been reported concerning HER2 status on clinical material, differences which generally have been attributed to methodological differences. Nevertheless, HER2 has been utilized for targeted therapy of prostate cancer in a number of preclinical studies and is still regarded as an exciting target molecule. In this study, the HER2 status of three widely used prostate cancer cell lines and corresponding xenografts has been analysed. By use of validated and FDA approved analytical staining techniques none of these cell lines or xenografts were shown to overexpress/amplify HER2, as demonstrated by immunohistochemistry and fluorescence in situ hybridization. These findings are important for the interpretation and understanding of the therapeutic effects when developing drugs targeting HER2 in prostate cancer cell lines and also emphasize the importance of using broad and validated analytical techniques.
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| 46. |
- Wu, X. P., et al.
(författare)
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Alternative Cytotoxic Effects of the Postulated IGF-IR Inhibitor Picropodophyllin In Vitro
- 2013
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Ingår i: Molecular Cancer Therapeutics. - : American Association for Cancer Research (AACR). - 1535-7163 .- 1538-8514. ; 12:8, s. 1526-1536
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Tidskriftsartikel (refereegranskat)abstract
- The insulin-like growth factor-1 (IGF-I) and its receptors play an important role in transformation and progression of several malignancies. Inhibitors of this pathway have been developed and evaluated but generally performed poorly in clinical trials, and several drug candidates have been abandoned. The cyclolignan picropodophyllin (PPP) has been described as a potent and selective IGF-IR inhibitor and is currently undergoing clinical trials. We investigated PPP's activity in panels of human cancer cell lines (e. g., esophageal squamous carcinoma cell lines) but found no effects on the phosphorylation or expression of IGF-IR. Nor was the cytotoxic activity of PPP related to the presence or spontaneous phosphorylation of IGF-IR. However, its activity correlated with that of known tubulin inhibitors, and it destabilized microtubule assembly at cytotoxic concentrations also achievable in patients. PPP is a stereoisomer of podophyllotoxin (PPT), a potent tubulin inhibitor, and an equilibrium between the two has previously been described. PPPcould thus potentially act as a reservoir for the continuous generation of low doses of PPT. Interestingly, PPP also inhibited downstream signaling from tyrosine kinase receptors, including the serine/threonine kinase Akt. This effect is associated with microtubule-related downregulation of the EGF receptor, rather than the IGF-IR. These results suggest that the cytotoxicity and pAkt inhibition observed following treatment with the cyclolignan PPP in vitro result from microtubule inhibition (directly or indirectly by spontaneous PPT formation), rather than any effect on IGF-IR. It is also suggested that PPT should be used as a reference compound in all future studies on PPP. (C)2013 AACR.
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