| 1. |
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| 2. |
- Santangelo, James S., et al.
(author)
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Global urban environmental change drives adaptation in white clover
- 2022
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
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Journal article (peer-reviewed)abstract
- Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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| 3. |
- Iacopetta, B, et al.
(author)
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Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study.
- 2006
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In: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. - : Elsevier BV. - 0923-7534. ; 17:5, s. 842-7
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Journal article (peer-reviewed)abstract
- BACKGROUND: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (< or=20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity. MATERIALS AND METHODS: TP53 mutations within a large, international database of CRC (n = 3583) were classified according to functional status for transactivation. RESULTS: Inactive TP53 mutations were found in 29% of all CRCs and were more frequent in rectal (32%) than proximal colon (22%) tumours (P < 0.001). Higher frequencies of inactive TP53 mutations were also seen in advanced stage tumours (P = 0.0003) and in tumours with the poor prognostic features of vascular (P = 0.006) and lymphatic invasion (P = 0.002). Inactive TP53 mutations were associated with significantly worse outcome only in patients with Dukes' stage D tumours (RR = 1.71, 95%CI 1.25-2.33, P < 0.001). Patients with Dukes' C stage tumours appeared to gain a survival benefit from 5-fluorouracil-based chemotherapy regardless of TP53 functional status for transactivation ability. CONCLUSIONS: Mutations that inactivate the transactivational ability of TP53 are more frequent in advanced CRC and are associated with worse prognosis in this stage of disease.
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| 4. |
- Abend, M., et al.
(author)
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RENEB Inter-Laboratory Comparison 2021 : The Gene Expression Assay
- 2023
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In: Radiation Research. - 0033-7587 .- 1938-5404. ; 199:6, s. 598-615
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Journal article (peer-reviewed)abstract
- Early and high-throughput individual dose estimates are essential following large-scale radiation exposure events. In the context of the Running the European Network for Biodosimetry and Physical Dosimetry (RENEB) 2021 exercise, gene expression assays were conducted and their corresponding performance for dose-assessment is presented in this publication. Three blinded, coded whole blood samples from healthy donors were exposed to 0, 1.2 and 3.5 Gy X-ray doses (240 kVp, 1 Gy/min) using the X-ray source Yxlon. These exposures correspond to clinically relevant groups of unexposed, low dose (no severe acute health effects expected) and high dose exposed individuals (requiring early intensive medical health care). Samples were sent to eight teams for dose estimation and identification of clinically relevant groups. For quantitative reverse transcription polymerase chain reaction (qRT-PCR) and microarray analyses, samples were lysed, stored at 20°C and shipped on wet ice. RNA isolations and assays were run in each laboratory according to locally established protocols. The time-to-result for both rough early and more precise later reports has been documented where possible. Accuracy of dose estimates was calculated as the difference between estimated and reference doses for all doses (summed absolute difference, SAD) and by determining the number of correctly reported dose estimates that were defined as ±0.5 Gy for reference doses <2.5 Gy and ±1.0 Gy for reference doses >3 Gy, as recommended for triage dosimetry. We also examined the allocation of dose estimates to clinically/diagnostically relevant exposure groups. Altogether, 105 dose estimates were reported by the eight teams, and the earliest report times on dose categories and estimates were 5 h and 9 h, respectively. The coefficient of variation for 85% of all 436 qRT-PCR measurements did not exceed 10%. One team reported dose estimates that systematically deviated several-fold from reported dose estimates, and these outliers were excluded from further analysis. Teams employing a combination of several genes generated about two-times lower median SADs (0.8 Gy) compared to dose estimates based on single genes only (1.7 Gy). When considering the uncertainty intervals for triage dosimetry, dose estimates of all teams together were correctly reported in 100% of the 0 Gy, 50% of the 1.2 Gy and 50% of the 3.5 Gy exposed samples. The order of dose estimates (from lowest to highest) corresponding to three dose categories (unexposed, low dose and highest exposure) were correctly reported by all teams and all chosen genes or gene combinations. Furthermore, if teams reported no exposure or an exposure >3.5 Gy, it was always correctly allocated to the unexposed and the highly exposed group, while low exposed (1.2 Gy) samples sometimes could not be discriminated from highly (3.5 Gy) exposed samples. All teams used FDXR and 78.1% of correct dose estimates used FDXR as one of the predictors. Still, the accuracy of reported dose estimates based on FDXR differed considerably among teams with one team's SAD (0.5 Gy) being comparable to the dose accuracy employing a combination of genes. Using the workflow of this reference team, we performed additional experiments after the exercise on residual RNA and cDNA sent by six teams to the reference team. All samples were processed similarly with the intention to improve the accuracy of dose estimates when employing the same workflow. Re-evaluated dose estimates improved for half of the samples and worsened for the others. In conclusion, this inter-laboratory comparison exercise enabled (1) identification of technical problems and corrections in preparations for future events, (2) confirmed the early and high-throughput capabilities of gene expression, (3) emphasized different biodosimetry approaches using either only FDXR or a gene combination, (4) indicated some improvements in dose estimation with FDXR when employing a similar methodology, which requires further research for the final conclusion and (5) underlined the applicability of gene expression for identification of unexposed and highly exposed samples, supporting medical management in radiological or nuclear scenarios.
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| 8. |
- Bielecki, Johan, 1982, et al.
(author)
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Electrospray sample injection for single-particle imaging with x-ray lasers
- 2019
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In: Science advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 5:5
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Journal article (peer-reviewed)abstract
- The possibility of imaging single proteins constitutes an exciting challenge for x-ray lasers. Despite encouraging results on large particles, imaging small particles has proven to be difficult for two reasons: not quite high enough pulse intensity from currently available x-ray lasers and, as we demonstrate here, contamination of the aerosolized molecules by nonvolatile contaminants in the solution. The amount of contamination on the sample depends on the initial droplet size during aerosolization. Here, we show that, with our electrospray injector, we can decrease the size of aerosol droplets and demonstrate virtually contaminant-free sample delivery of organelles, small virions, and proteins. The results presented here, together with the increased performance of next-generation x-ray lasers, constitute an important stepping stone toward the ultimate goal of protein structure determination from imaging at room temperature and high temporal resolution.
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| 9. |
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| 10. |
- Correggi, M., et al.
(author)
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Vortex patterns in the almost-bosonic anyon gas
- 2019
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In: Europhysics letters. - : Institute of Physics Publishing. - 0295-5075 .- 1286-4854. ; 126:2
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Journal article (peer-reviewed)abstract
- We study theoretically and numerically the ground state of a gas of 2D Abelian anyons in an external trapping potential. We treat anyon statistics in the magnetic gauge picture, perturbatively around the bosonic end. This leads to a mean-field energy functional, whose ground state displays vortex lattices similar to those found in rotating Bose-Einstein condensates. A crucial difference is, however, that the vortex density is proportional to the underlying matter density of the gas.
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| 11. |
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| 12. |
- Elia, M, et al.
(author)
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Enteral (oral or tube administration) nutritional support and eicosapentaenoic acid in patients with cancer: a systematic review.
- 2006
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In: International journal of oncology. - 1019-6439. ; 28:1, s. 5-23
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Journal article (peer-reviewed)abstract
- The aim of this systematic review was to determine the efficacy and potential benefits of enteral nutritional support [oral nutritional supplements (ONS) or enteral tube feeding (ETF)], and eicosapentaenoic acid (EPA, free acid, ethyl esters or fish oil; provided as capsules or enriched ONS or ETF) in patients with cancer. Clinical studies were identified using electronic databases, and studies were selected according to predetermined criteria. For each treatment modality (chemo/radiotherapy, surgery, and palliative care), the comparisons of interest were nutritional support vs. routine care (no nutritional support), EPA supplement (capsule or enriched ONS or ETF) vs. routine care (no supplement or standard supplement), ETF vs. parenteral nutrition (PN). The reviewed outcomes were dietary intake, anthropometry, clinical (mortality, length of hospital stay, complications, and quality of life) and haematological/biochemical (white blood cell count, serum transferrin and albumin, CD3-positive lymphocytes, and inflammatory markers). Meta-analyses were performed where possible. In patients undergoing radiotherapy, meta-analysis showed that ONS significantly increase dietary intake (381 kcal/day, 95% CI 193 to 569 in 3 RCTs) compared to routine care. In patients undergoing surgery, meta-analyses showed that ETF results in a significantly shorter length of hospital stay (1.72 fewer days, 95% CI 0.90 to 2.54 in 8 RCTs), lower incidence of any complications (OR 0.62, 95% CI 0.50 to 0.77 in 4 RCTs) and infectious complications (OR 0.67, 95% CI 0.55 to 0.82 in 11 RCTs) and lower sepsis scores (2.21 points, 95% CI 1.49 to 2.92 in 2 RCTs), but no difference in mortality (OR 0.72, 95% CI 0.40 to 1.29 in 7 RCTs) compared to PN. There was also no difference in mortality between ONS or ETF vs. routine care in patients undergoing chemotherapy/radiotherapy (OR 1.00, 95% CI 0.62-1.61 in 4 RCTs) or surgery (OR 2.44, 95% CI 0.75 to 7.95 in 4 RCTs). Individual studies of EPA supplementation as capsules showed improvements in survival, complications and inflammatory markers in patients undergoing bone marrow transplant (BMT). In palliative care patients receiving EPA-enriched ONS or capsules, there were inconsistent positive effects on survival and quality of life. In those undergoing surgery, EPA-enriched ETF had no effect. Further research is required to elucidate the clinical efficacy of enteral nutrition support, including the potential benefits of EPA supplementation, in patients with cancer.
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| 13. |
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| 14. |
- Gelin, Johan, 1948, et al.
(author)
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Treatment efficacy of intermittent claudication by surgical intervention, supervised physical exercise training compared to no treatment in unselected randomised patients I: one year results of functional and physiological improvements.
- 2001
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In: European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery. - : Elsevier BV. - 1078-5884. ; 22:2, s. 107-13
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Journal article (peer-reviewed)abstract
- OBJECTIVES: to compare the effect of surgery, exercise and simple observation on maximum exercise power in claudicants. Design: prospective, randomised study. METHODS: a total of 264 unselected claudicants were randomised to supervised exercise training, invasive treatment (open surgical or endovascular procedures) or observation. One year treatment outcomes were analysed on an intention to-treat basis. RESULTS: invasively treated patients showed a significant improvement in maximum walking power, stopping distance, post-ischaemic blood flow and big toe pressure at one year. Patients randomised to physical exercise training or to the control group did not improve in any outcome measure. CONCLUSION: invasive treatment increased walking capacity, leg blood pressure and flow. Supervised physical exercise training offered no therapeutic advantage compared to untreated controls.
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| 15. |
- Godhe, Anna, 1967, et al.
(author)
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Physical barriers and environmental gradients cause spatial and temporal genetic differentiation of an extensive algal bloom
- 2016
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In: Journal of Biogeography. - : John Wiley & Sons. - 0305-0270 .- 1365-2699. ; 43:6, s. 1130-1142
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Journal article (peer-reviewed)abstract
- Aim: To test if a phytoplankton bloom is panmictic, or whether geographical and environmental factors cause spatial and temporal genetic structure.Location: Baltic Sea.Method: During four cruises, we isolated clonal strains of the diatom Skeletonema marinoifrom 9 to 10 stations along a 1132 km transect and analysed the genetic structure using eight microsatellites. Using F-statistics and Bayesian clustering analysis we determined if samples were significantly differentiated. A seascape approach was applied to examine correlations between gene flow and oceanographic connectivity, and combined partial Mantel test and RDA based variation partitioning to investigate associations with environmental gradients.Results: The bloom was initiated during the second half of March in the southern and the northern- parts of the transect, and later propagated offshore. By mid-April the bloom declined in the south, whereas high phytoplankton biomass was recorded northward. We found two significantly differentiated populations along the transect. Genotypes were significantly isolated by distance and by the south–north salinity gradient, which illustrated that the effects of distance and environment were confounded. The gene flow among the sampled stations was significantly correlated with oceanographic connectivity. The depletion of silica during the progression of the bloom was related to a temporal population genetic shift.Main conclusions: A phytoplankton bloom may propagate as a continuous cascade and yet be genetically structured over both spatial and temporal scales. The Baltic Sea spring bloom displayed strong spatial structure driven by oceanographic connectivity and geographical distance, which was enhanced by the pronounced salinity gradient. Temporal transition of conditions important for growth may induce genetic shifts and different phenotypic strategies, which serve to maintain the bloom over longer periods.
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| 16. |
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| 17. |
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| 18. |
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| 19. |
- Gong, T., et al.
(author)
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Understanding the relationship between asthma and autism spectrum disorder: a population-based family and twin study
- 2023
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In: Psychological Medicine. - : Cambridge University Press (CUP). - 0033-2917 .- 1469-8978. ; 53:7, s. 3096-3104
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Journal article (peer-reviewed)abstract
- Background There is some evidence that autism spectrum disorder (ASD) frequently co-occurs with immune-mediated conditions including asthma. We aimed to explore the familial co-aggregation of ASD and asthma using different genetically informed designs. Methods We first examined familial co-aggregation of asthma and ASD in individuals born in Sweden from 1992 to 2007 (n = 1 569 944), including their full- and half-siblings (n = 1 704 388 and 356 544 pairs) and full cousins (n = 3 921 890 pairs), identified using Swedish register data. We then applied quantitative genetic modeling to siblings (n = 620 994 pairs) and twins who participated in the Child and Adolescent Twin Study in Sweden (n = 15 963 pairs) to estimate the contribution of genetic and environmental factors to the co-aggregation. Finally, we estimated genetic correlations between traits using linkage disequilibrium score regression (LDSC). Results We observed a within-individual association [adjusted odds ratio (OR) 1.33, 95% confidence interval (CI) 1.28-1.37] and familial co-aggregation between asthma and ASD, and the magnitude of the associations decreased as the degree of relatedness decreased (full-siblings: OR 1.44, 95% CI 1.38-1.50, maternal half-siblings: OR 1.28, 95% CI 1.18-1.39, paternal half-siblings: OR 1.05, 95% CI 0.96-1.15, full cousins: OR 1.06, 95% CI 1.03-1.09), suggesting shared familial liability. Quantitative genetic models estimated statistically significant genetic correlations between ASD traits and asthma. Using the LDSC approach, we did not find statistically significant genetic correlations between asthma and ASD (coefficients between -0.09 and 0.12). Conclusions Using different genetically informed designs, we found some evidence of familial co-aggregation between asthma and ASD, suggesting the weak association between these disorders was influenced by shared genetics.
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| 20. |
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| 21. |
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| 22. |
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| 23. |
- Hinkula, J, et al.
(author)
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Genetic immunization with multiple HIV-1 genes provides protection against HIV-1/MuLV pseudovirus challenge in vivo
- 2004
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In: Cells, tissues, organs. - : S. Karger AG. - 1422-6405 .- 1422-6421. ; 177:3, s. 169-184
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Journal article (peer-reviewed)abstract
- Superinfection by HIV-1 of a cell line containing the complete murine leukemia virus (MuLV) genome was shown to give rise to pseudotyped HIV-1/MuLV. Such superinfection was successful with certain strains of HIV-1 subtypes A–D. Primary spleen cells and cells of the peritoneal cavity of immunocompetent mice of the C57Bl/6 strain were infectable with the pseudotype HIV-1/MuLV and secreted HIV-1 in vitro and in vivo. In contrast, the murine cell lines, NIH 3T3, myeloma cell line Sp2/0, and two murine hybridoma cell lines were relatively resistant to infection and produced no or little HIV. After primary murine spleen cells had been infected with pseudotyped HIV-1 and transferred to C57Bl/6 mice, replication-competent HIV-1 was obtained from the peritoneal cavity for at least 10–14 days. High amounts (>10<sup>5</sup> vRNA copies/ml) of HIV-1 vRNA could be measured in the peritoneal fluid. Presence of HIV-1 proviral DNA was detectable in cells from the peritoneal cavity for up to 24 days after infected cell transfer. Active reverse transcriptase representing both HIV-1 and C-type murine retroviruses was detected in the peritoneal washes. The HIV-infected spleen cells injected into the peritoneal cavity elicited HIV-1-specific cellular immune responses to p24gag, gp160Env, Nef, Tat and Rev. Mice immunized with HIV-1 DNA, but not with HIV-1 protein, cleared their HIV-1-infected cells within 10–14 days after challenge with HIV-1/MuLV-infected syngeneic spleen cells. This novel model system of primarily cellular reactivity to HIV-1-infected cells in vivo may become useful for assaying experimental HIV-1 immunization schedules.
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| 24. |
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| 25. |
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| 26. |
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| 27. |
- Lundholm, Ida V., et al.
(author)
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Considerations for three-dimensional image reconstruction from experimental data in coherent diffractive imaging
- 2018
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In: IUCrJ. - : International Union of Crystallography. - 2052-2525. ; 5, s. 531-541
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Journal article (peer-reviewed)abstract
- Diffraction before destruction using X-ray free-electron lasers (XFELs) has the potential to determine radiation-damage-free structures without the need for crystallization. This article presents the three-dimensional reconstruction of the Melbournevirus from single-particle X-ray diffraction patterns collected at the LINAC Coherent Light Source (LCLS) as well as reconstructions from simulated data exploring the consequences of different kinds of experimental sources of noise. The reconstruction from experimental data suffers from a strong artifact in the center of the particle. This could be reproduced with simulated data by adding experimental background to the diffraction patterns. In those simulations, the relative density of the artifact increases linearly with background strength. This suggests that the artifact originates from the Fourier transform of the relatively flat background, concentrating all power in a central feature of limited extent. We support these findings by significantly reducing the artifact through background removal before the phase-retrieval step. Large amounts of blurring in the diffraction patterns were also found to introduce diffuse artifacts, which could easily be mistaken as biologically relevant features. Other sources of noise such as sample heterogeneity and variation of pulse energy did not significantly degrade the quality of the reconstructions. Larger data volumes, made possible by the recent inauguration of high repetition-rate XFELs, allow for increased signal-to-background ratio and provide a way to minimize these artifacts. The anticipated development of three-dimensional Fourier-volume-assembly algorithms which are background aware is an alternative and complementary solution, which maximizes the use of data.
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| 28. |
- Lundholm, Lovisa, et al.
(author)
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Gene expression profiling identifies liver X receptor alpha as an estrogen-regulated gene in mouse adipose tissue.
- 2004
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In: Journal of molecular endocrinology. - : Bioscientifica. - 0952-5041 .- 1479-6813. ; 32:3, s. 879-92
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Journal article (peer-reviewed)abstract
- Estrogens reduce adipose tissue mass in both humans and animals. The molecular mechanisms for this effect are, however, not well characterized. We took a gene expression profiling approach to study the direct effects of estrogen on mouse white adipose tissue (WAT). Female ovariectomized mice were treated for 10, 24 and 48 h with 17beta-estradiol or vehicle. RNA was extracted from gonadal fat and hybridized to Affymetrix MG-U74Av2 arrays. 17beta-Estradiol was shown to decrease mRNA expression of liver X receptor (LXR) alpha after 10 h of treatment compared with the vehicle control. The expression of several LXRalpha target genes, such as sterol regulatory element-binding protein 1c, apolipoprotein E, phospholipid transfer protein, ATP-binding cassette A1 and ATP-binding cassette G1, was similarly decreased. We furthermore identified a 1.5 kb LXRalpha promoter fragment that is negatively regulated by estrogen. Several genes involved in lipogenesis and lipolysis were identified as novel targets that could mediate estrogenic effects on adipose tissue. Finally, we show that ERalpha is the main estrogen receptor expressed in mouse white adipose tissue (WAT) with mRNA levels several hundred times higher than those of ERbeta mRNA.
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| 29. |
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| 32. |
- Lundholm, L, et al.
(author)
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The estrogen receptor {alpha}-selective agonist propyl pyrazole triol improves glucose tolerance in ob/ob mice; potential molecular mechanisms
- 2008
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In: Journal of Endocrinology. - 0022-0795 .- 1479-6805. ; 199:2, s. 275-286
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Journal article (peer-reviewed)abstract
- The aim of this study was to validate the role of estrogen receptor alpha (ERalpha) signaling in the regulation of glucose metabolism, and to compare the molecular events upon treatment with the ERalpha-selective agonist propyl pyrazole triol (PPT) or 17beta-estradiol (E(2)) in ob/ob mice. Female ob/ob mice were treated with PPT, E(2) or vehicle for 7 or 30 days. Intraperitoneal glucose and insulin tolerance tests were performed, and insulin secretion was determined from isolated islets. Glucose uptake was assayed in isolated skeletal muscle and adipocytes. Gene expression profiling in the liver was performed using Affymetrix microarrays, and the expression of selected genes was studied by real-time PCR analysis. PPT and E(2) treatment improved glucose tolerance and insulin sensitivity. Fasting blood glucose levels decreased after 30 days of PPT and E(2) treatment. However, PPT and E(2) had no effect on insulin secretion from isolated islets. Basal and insulin-stimulated glucose uptake in skeletal muscle and adipose tissue were similar in PPT and vehicle-treated ob/ob mice. Hepatic lipid content was decreased after E(2) treatment. In the liver, treatment with E(2) and PPT increased and decreased the respective expression levels of the transcription factor signal transducer and activator of transcription 3, and of glucose-6-phosphatase. In summary, our data demonstrate that PPT exerts anti-diabetic effects, and these effects are mediated via ERalpha.
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| 33. |
- Makitalo, B, et al.
(author)
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Enhanced cellular immunity and systemic control of SHIV infection by combined parenteral and mucosal administration of a DNA prime MVA boost vaccine regimen
- 2004
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In: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 85:Pt 8, s. 2407-2419
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Journal article (peer-reviewed)abstract
- The immunogenicity and protective efficacy of a DNA and recombinant modified vaccinia Ankara (MVA) vaccine administered by two different routes were investigated. DNA expressing HIV-1 IIIB env, gag, RT, rev, tat and nef, and MVA expressing HIV-1 IIIB nef, tat and rev and simian immunodeficiency virus (SIV) macJ5 gag/pol and vaccinia HIV-1 env, were used as immunogens. Four cynomolgus macaques received DNA intramuscularly (i.m.) at month 0 and intrarectally (i.r.) and intra-orally (i.o.) at 2 months, followed by MVA i.m. at 4 months and i.r. and i.o. at 8 months. Another group of four monkeys received the same immunogens but only i.m.. Overall, stronger cellular immune responses measured by ELISPOT and T-cell proliferation assay were detected in the group primed i.m. and boosted mucosally. Following homologous intravenous simian-human immunodeficiency virus (SHIV) challenge, one of eight vaccinated animals was completely protected. This monkey, immunized i.m. and i.r.+i.o., exhibited the highest levels of HIV Env, Nef and Tat antibodies, high HIV Tat cytotoxic T-lymphocyte activity and T-lymphocyte proliferative responses to HIV Env. Four weeks post-challenge none of the monkeys immunized i.m. and i.r.+i.o., and only two out of four animals immunized i.m., demonstrated detectable plasma viral RNA levels. In contrast, all eight control animals had demonstrable plasma viral RNA levels 4 weeks post-challenge. Thus, stronger cellular immune responses and reduction of challenge virus burden were demonstrated in animals immunized i.m. as well as mucosally, compared with animals immunized i.m. only. The breadth and magnitude of the induced immune responses correlated with protective efficacy.
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| 34. |
- Martin, Lisa, et al.
(author)
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Diagnostic Criteria for the Classification of Cancer-Associated Weight Loss.
- 2015
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In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 33:1, s. 90-99
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Journal article (peer-reviewed)abstract
- Existing definitions of clinically important weight loss (WL) in patients with cancer are unclear and heterogeneous and do not consider current trends toward obesity.
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| 36. |
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| 38. |
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| 39. |
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| 40. |
- Sandström, R, et al.
(author)
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The effect of recombinant human IGF-I on protein metabolism in post-operative patients without nutrition compared to effects in experimental animals.
- 1995
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In: European journal of clinical investigation. - 0014-2972. ; 25:10, s. 784-92
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Journal article (peer-reviewed)abstract
- This study has evaluated the effects of recombinant human insulin-like growth factor I (rhIGF-I) to moderately stressed post-operative patients provided with dextrose as the only exogeneous substrate. Thirty patients who underwent elective colorectal surgery were randomized to receive either rhIGF-I (80 micrograms kg-1 bw) subcutaneously twice daily or placebo injections in a double-blind parallel group design. Nitrogen balance, urinary 3-methyl-histidine excretion plasma growth hormone (GH), serum cortisol, IGF-I binding proteins (IGFBP-1,3), glomerular filtration rate, plasma amino acid concentrations and whole-body energy expenditures were measured as effector variables during days 1-5 post-operatively. Animal and isolated tissue experiments were performed as additional control experiments to confirm cellular effectiveness of the recombinant material. rhIGF-I increased significantly the glomerular filtration rate and prevented the adaptive decrease in whole-body energy expenditure in response to partial starvation in the postoperative period. Serum and plasma concentrations of IGFBP-1,3 cortisol, blood glucose and amino acids were not significantly influenced by rhIGF-I administration, while plasma GH levels decreased significantly as expected. rhIGF-I had no effect on either nitrogen balance or protein breakdown (3-methylhistidine excretion) in post-operative patients on dextrose supplementation only, although plasma concentrations of IGF-I increased from 130-140 ng mL-1 to a range of 300-450 ng mL-1. In contrast, IGF-I stimulated the synthesis of both globular and myofibrillar proteins (+50%, P < 0.01), when given as a single dose (100 micrograms kg-1) 2 h before measurements of protein synthesis in skeletal muscles of overnight fasted adult mice. This stimulatory effect by IGF-I (1 microgram mL-1) was also confirmed by measurements of skeletal muscle protein synthesis in vitro (+40%, P < 0.05). Orally re-fed mice had a normal transcription of IGF-I mRNA in skeletal muscle cells, while overnight fasted mice showed a trend to down-regulated transcription. Our results demonstrate that rhIGF-I has several significant physiological effects, without major side-effects, when supplied to partially starved patients in the post-operative phase. The lack of a whole-body nitrogen sparing effect by rhIGF-I alone to post-operative patients is not clear, but was most likely explained by subnormal plasma concentrations of amino acids.
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| 41. |
- Svanberg, Elisabeth, 1961, et al.
(author)
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rhIGF-I/IGFBP-3 complex, but not free rhIGF-I, supports muscle protein biosynthesis in rats during semistarvation.
- 2000
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In: European journal of clinical investigation. - 0014-2972. ; 30:5, s. 438-46
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Journal article (peer-reviewed)abstract
- BACKGROUND: The aim of this study was to evaluate the effect of insulin like growth factor-I (rhIGF-I) in complex with binding protein 3 (IGFBP 3) compared to the effect of free IGF-I on muscle protein biosynthesis in undernourished animals. METHODS: Three groups of female Sprague-Dawley rats (200 g) were initially semi-starved for 3 days and then treated with saline (controls), rhIGF-I (1 microg g-1) or equimolar amounts of rhIGF-I/rhIGFBP-3 complex (5 microg g-1) i.v. twice daily for 3 days during continuous semistarvation. Protein metabolism in hind limb skeletal muscle was studied by incorporation of L-[14C-U]phenylalanine into proteins, western blot determination of translation initiation factors involved in the binding of the 40S ribosomal subunit to mRNA, and quantification of mRNA content for IGF-I, IGF-IR and GH-R. Plasma measurements of insulin, IGF-I and amino acids were also performed. RESULTS: rhIGF-I/rhIGFBP-3, but not rhIGF-I alone, stimulated protein synthesis by 177 +/- 26% (P
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| 42. |
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| 43. |
- Taft, Charles, 1950, et al.
(author)
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Treatment efficacy of intermittent claudication by invasive therapy, supervised physical exercise training compared to no treatment in unselected randomised patients II: one-year results of health-related quality of life.
- 2001
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In: European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery. - : Elsevier BV. - 1078-5884. ; 22:2, s. 114-23
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Journal article (peer-reviewed)abstract
- OBJECTIVE: to compare the effectiveness of invasive therapy, supervised physical training and no treatment in terms of health-related quality of life (HRQL) in patients with intermittent claudication (IC). DESIGN: a prospective, randomised, controlled study. MATERIALS: a total of 253 unselected patients with stable IC were sequentially randomised into 3 balanced treatment groups. At 1 year follow-up data from a battery of generic and disease specific HRQL questionnaires, and global indices of quality of life and physical condition were available in 171 patients. RESULTS: compared with a non-diseased reference group, claudicants were substantially limited in daily physical functioning, but little affected regarding emotional, cognitive and social functioning, or well-being. Invasive therapy yielded significantly greater improvements in some aspects of physical functioning and walk-related symptoms than training. Training was not superior to invasive therapy on any HRQL dimension and superior to no treatment on only one dimension. Treatment effects, however, were generally small-to-moderate and levels of physical dysfunction in all groups remained higher than reference values. CONCLUSIONS: invasive therapy is more effective than supervised training in alleviating illness-specific symptoms and improving certain aspects of physical functioning - the primary HRQL domains impacted on by IC and the principal goals of its treatment. However, since treatment effect sizes were at most moderate and given that untreated claudicants reported at most small deterioration in HRQL, the level of evidence supporting invasive therapy is modest.
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| 44. |
- Thysell, Elin, et al.
(author)
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Clinical and biological relevance of the transcriptomic-based prostate cancer metastasis subtypes MetA-C
- 2022
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In: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 16:4, s. 846-859
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Journal article (peer-reviewed)abstract
- To improve treatment of metastatic prostate cancer, the biology of metastases needs to be understood. We recently described three subtypes of prostate cancer bone metastases (MetA-C), based on differential gene expression. The aim of this study was to verify the clinical relevance of these subtypes and to explore their biology and relations to genetic drivers. Freshly-frozen metastasis samples were obtained as hormone-naive (n = 17), short-term castrated (n = 21), or castration-resistant (n = 65) from a total of 67 patients. Previously published sequencing data from 573 metastasis samples were also analyzed. Through transcriptome profiling and sample classification based on a set of predefined MetA-C-differentiating genes, we found that most metastases were heterogeneous for the MetA-C subtypes. Overall, MetA was the most common subtype, while MetB was significantly enriched in castration-resistant samples and in liver metastases, and consistently associated with poor prognosis. By gene set enrichment analysis, the phenotype of MetA was described by high androgen response, protein secretion and adipogenesis, MetB by high cell cycle activity and DNA repair, and MetC by epithelial-to-mesenchymal transition and inflammation. The MetB subtype demonstrated single nucleotide variants of RB transcriptional corepressor 1 (RB1) and loss of 21 genes at chromosome 13, including RB1, but provided independent prognostic value to those genetic aberrations. In conclusion, a distinct set of gene transcripts can be used to classify prostate cancer metastases into the subtypes MetA-C. The MetA-C subtypes show diverse biology, organ tropism, and prognosis. The MetA-C classification may be used independently, or in combination with genetic markers, primarily to identify MetB patients in need of complementary therapy to conventional androgen receptor-targeting treatments.
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| 45. |
- Yakaboylu, E., et al.
(author)
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Quantum impurity model for anyons
- 2020
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In: Physical Review B. - : American Physical Society (APS). - 2469-9950 .- 2469-9969. ; 102:14
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Journal article (peer-reviewed)abstract
- One of the hallmarks of quantum statistics, tightly entwined with the concept of topological phases of matter, is the prediction of anyons. Although anyons are predicted to be realized in certain fractional quantum Hall systems, they have not yet been unambiguously detected in experiment. Here we introduce a simple quantum impurity model, where bosonic or fermionic impurities turn into anyons as a consequence of their interaction with the surrounding many-particle bath. A cloud of phonons dresses each impurity in such a way that it effectively attaches fluxes or vortices to it and thereby converts it into an Abelian anyon. The corresponding quantum impurity model, first, provides a different approach to the numerical solution of the many-anyon problem, along with a concrete perspective of anyons as emergent quasiparticles built from composite bosons or fermions. More importantly, the model paves the way toward realizing anyons using impurities in crystal lattices as well as ultracold gases. In particular, we consider two heavy electrons interacting with a two-dimensional lattice crystal in a magnetic field, and show that when the impurity-bath system is rotated at the cyclotron frequency, impurities behave as anyons as a consequence of the angular momentum exchange between the impurities and the bath. A possible experimental realization is proposed by identifying the statistics parameter in terms of the mean-square distance of the impurities and the magnetization of the impurity-bath system, both of which are accessible to experiment. Another proposed application is impurities immersed in a two-dimensional weakly interacting Bose gas.
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| 46. |
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