| 1. |
- Bodén, Stina, et al.
(author)
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C-reactive Protein and Future Risk of Clinical and Molecular Subtypes of Colorectal Cancer
- 2020
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In: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 29:7, s. 1482-1491
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Journal article (peer-reviewed)abstract
- Background: Inflammation has been implicated in colorectal cancer etiology, but the relationship between C-reactive protein (CRP) and colorectal cancer risk is unclear. We aimed to investigate the association between prediagnostic plasma CRP concentrations and the risk of clinical and molecular colorectal cancer subtypes.Methods: We used prospectively collected samples from 1,010 matched colorectal cancer case-control pairs from two population-based cohorts in Northern Sweden, including 259 with repeated samples. Conditional logistic regression and linear mixed models were used to estimate relative risks of colorectal cancer, including subtypes based on BRAF and KRAS mutations, microsatellite instability status, tumor location, stage, lag time, and (using unconditional logistic regression) body mass index.Results: CRP was not associated with colorectal cancer risk, regardless of clinical or molecular colorectal cancer subtype. For participants with advanced tumors and blood samples <5 years before diagnosis, CRP was associated with higher risk [OR per 1 unit increase in natural logarithm (In) transformed CRP, 1.32; 95% confidence interval (CI), 1.01-1.73]. CRP levels increased over time, but average time trajectories were similar for cases and controls (P-interaction = 0.19).Conclusions: Our results do not support intertumoral heterogeneity as an explanation for previous inconsistent findings regarding the role of CRP in colorectal cancer etiology. The possible association in the subgroup with advanced tumors and shorter follow-up likely reflects undiagnosed cancer at baseline. Impact: Future efforts to establish the putative role of chronic, low-grade inflammation in colorectal cancer development will need to address the complex relationship between systemic inflammatory factors and tumor microenvironment, and might consider larger biomarker panels than CRP alone.
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| 2. |
- Bodén, Stina, et al.
(author)
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Plasma concentrations of gut hormones acyl ghrelin and peptide YY and subsequent risk of colorectal cancer and molecular tumor subtypes
- 2023
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In: Cancer Prevention Research. - : American Association for Cancer Research. - 1940-6207 .- 1940-6215. ; 16:2, s. 75-87
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Journal article (peer-reviewed)abstract
- Obesity and metabolic dysfunction are implicated in colorectal cancer development. Appetite-regulating gut hormones might have a role in colorectal cancer risk. We investigated whether circulating levels of the gut hormones ghrelin (analyzed as acyl ghrelin) and Peptide YY (PYY) were associated with subsequent colorectal cancer risk, including clinical and molecular tumor subtypes. We also provide descriptive data on these hormones in relation to background participant characteristics and metabolic biomarkers. This population-based study included 1,010 matched case-control pairs with a median of 12.3 years of follow-up. Acyl ghrelin and PYY were measured by multiplex immunoassay. Data on KRAS and BRAF mutations and microsatellite instability (MSI) status were available for 704 and 708 cases, respectively. Conditional logistic regression models estimated association to colorectal cancer risk. Partial correlation and linear regression were used to investigate relationships between background and metabolic variables and variation in plasma gut hormone concentrations. Acyl ghrelin was not clearly associated with colorectal cancer risk (multivariable OR per 1 SD increase: 1.11; 95% CI, 1.00-1.23). Positive associations were observed for specific subtypes, in particular BRAF-mutated colorectal cancer and right-sided colon cancer, although with nonsignificant heterogeneity. PYY was not related to colorectal cancer risk (multivariable OR per 1 SD: 1.04; 95% CI, 0.95-1.14) or any tumor subtype. In the control participants, ghrelin was inversely correlated with BMI, and PYY was positively correlated with C-peptide and insulin levels. These findings provide limited support for a possible role for ghrelin in colorectal cancer development, primarily in specific anatomical and molecular tumor subtypes.PREVENTION RELEVANCE: The findings of this study do not support a major role for the metabolic gut hormones ghrelin and PYY in colorectal cancer development but suggest the possibility of an involvement for ghrelin in specific tumor subtypes. Elucidating subtype-specific risk factors and mechanisms of carcinogenesis may have implications for precision prevention.
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| 3. |
- Dahl, Martin, 1984-, et al.
(author)
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A 2,000-Year Record of Eelgrass (Zostera marina L.) : Colonization Shows Substantial Gains in Blue Carbon Storage and Nutrient Retention
- 2024
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In: Global Biogeochemical Cycles. - : John Wiley & Sons. - 0886-6236 .- 1944-9224. ; 38:3
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Journal article (peer-reviewed)abstract
- Assessing historical environmental conditions linked to habitat colonization is important for understanding long-term resilience and improving conservation and restoration efforts. Such information is lacking for the seagrass Zostera marina, an important foundation species across cold-temperate coastal areas of the Northern Hemisphere. Here, we reconstructed environmental conditions during the last 14,000 years from sediment cores in two eelgrass (Z. marina) meadows along the Swedish west coast, with the main aims to identify the time frame of seagrass colonization and describe subsequent biogeochemical changes following establishment. Based on vegetation proxies (lipid biomarkers), eelgrass colonization occurred about 2,000 years ago after geomorphological changes that resulted in a shallow, sheltered environment favoring seagrass growth. Seagrass establishment led to up to 20- and 24-fold increases in sedimentary carbon and nitrogen accumulation rates, respectively. This demonstrates the capacity of seagrasses as efficient ecosystem engineers and their role in global change mitigation and adaptation through CO2 removal, and nutrient and sediment retention. By combining regional climate projections and landscape models, we assessed potential climate change effects on seagrass growth, productivity and distribution until 2100. These predictions showed that seagrass meadows are mostly at risk from increased sedimentation and hydrodynamic changes, while the impact from sea level rise alone might be of less importance in the studied area. This study showcases the positive feedback between seagrass colonization and environmental conditions, which holds promise for successful conservation and restoration efforts aimed at supporting climate change mitigation and adaptation, and the provision of several other crucial ecosystem services. © 2024. The Authors.
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| 4. |
- Dahl, Martin, 1984-, et al.
(author)
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First assessment of seagrass carbon accumulation rates in Sweden: A field study from a fjord system at the Skagerrak coast
- 2023
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In: PLoS Climate. - : Public Library of Science (PLoS). - 2767-3200. ; 2:1
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Journal article (peer-reviewed)abstract
- Seagrass meadows are globally important blue carbon sinks. In northern cold-temperate regions, eelgrass (Zostera marina) is the dominant seagrass species, and although their sedimentary carbon stocks have been quantified across regions, information regarding the CO2 withdrawal capacity as carbon sinks remains scarce. Here we assessed the carbon (Corg) accumulation rates (CARs) and stocks as well as the organic matter sources in five seagrass meadows in the Gullmar Fjord area on the Swedish Skagerrak coast. We found that the mean (±SD) CAR was 14 ± 3 g Corg m-2 yr-1 over the last ~120–140 years (corresponding to a yearly uptake of 52.4 ± 12.6 g CO2 m-2). The carbon sink capacity is in line with other Z. marina areas but relatively low compared to other seagrass species and regions globally. About half of the sedimentary carbon accumulation (7.1 ± 3.3 g Corg m-2 yr-1) originated from macroalgae biomass, which highlights the importance of non-seagrass derived material for the carbon sink function of seagrass meadows in the area. The Corg stocks were similar among sites when comparing at a standardized depth of 50 cm (4.6–5.9 kg Corg m-2), but showed large variation when assessed for the total extent of the cores (ranging from 0.7 to 20.6 kg Corg m-2 for sediment depths of 11 to at least 149 cm). The low sediment accretion rates (1.18–1.86 mm yr-1) and the relatively thick sediment deposits (with a maximum of >150 cm of sediment depth) suggests that the carbon stocks have likely been accumulated for an extended period of time, and that the documented loss of seagrass meadows in the Swedish Skagerrak region and associated erosion of the sediment could potentially have offset centuries of carbon sequestration.
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| 7. |
- Li, Xingru, et al.
(author)
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Ex Vivo Organoid Cultures Reveal the Importance of the Tumor Microenvironment for Maintenance of Colorectal Cancer Stem Cells
- 2020
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In: Cancers. - : MDPI. - 2072-6694. ; 12:4
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Journal article (peer-reviewed)abstract
- Colorectal cancer (CRC) is a heterogeneous disease, with varying clinical presentations and patient prognosis. Different molecular subgroups of CRC should be treated differently and therefore, must be better characterized. Organoid culture has recently been suggested as a good model to reflect the heterogeneous nature of CRC. However, organoid cultures cannot be established from all CRC tumors. The study examines which CRC tumors are more likely to generate organoids and thus benefit from ex vivo organoid drug testing. Long-term organoid cultures from 22 out of 40 CRC tumor specimens were established. It was found that organoid cultures were more difficult to establish from tumors characterized as microsatellite instable (MSI), BRAF-mutated, poorly differentiated and/or of a mucinous type. This suggests that patients with such tumors are less likely to benefit from ex vivo organoid drug testing, but it may also suggest biological difference in tumor growth. RNA sequencing analysis of tumor sections revealed that the in vivo maintenance of these non-organoid-forming tumors depends on factors related to inflammation and pathogen exposure. Furthermore, using TCGA data we could show a trend towards a worse prognosis for patients with organoid-forming tumors, suggesting also clinical differences. Results suggest that organoids are more difficult to establish from tumors characterized as MSI, BRAF-mutated, poorly differentiated and/or of a mucinous type. We further suggest that the maintenance of cell growth of these tumors in vivo may be promoted by immune-related factors and other stromal components within the tumor microenvironment.
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| 8. |
- Lundberg, Ida, et al.
(author)
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MicroRNA expression in KRAS- and BRAF-mutated colorectal cancers
- 2018
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In: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 38:2, s. 677-683
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Journal article (peer-reviewed)abstract
- Background/Aim: KRAS and BRAF are two genes commonly mutated in colorectal cancer (CRC). Even though BRAF is a downstream target of KRAS in the MAPK signalling pathway, KRAS- and BRAF-mutated CRCs are found to display several different clinical and histopathological features. We investigated whether a differential expression of microRNAs (miRNAs) could explain the clinicopathological differences seen between KRAS-and BRAF-mutated CRCs.Materials and Methods: Using a PCR array, we analyzed the expression of 84 different miRNAs in CRC cell lines wild-type in KRAS and BRAF, or mutated in KRAS or BRAF.Results: Ten miRNAs were selected for further analyses in tumor tissue specimens (let-7a, let-7i, miR-10a, miR-10b, miR-31, miR-100, miR-181a, miR-181b, miR-372, and miR-373). BRAF-mutated tumors were found to express significantly higher levels of miR-31 as well as significantly lower levels of miR-373, compared to wild-type tumors.Conclusion: Our results suggest that KRAS and BRAF-mutated CRCs may have different miRNA signatures compared to CRC tumors wild-type in KRAS and BRAF. However, no difference in expression levels between KRAS-and BRAF-mutated tumors was evident for the miRNAs analyzed in this study.
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| 9. |
- Löfgren, Bjarne, et al.
(author)
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An Increase in School-Based Physical Education Increases Muscle Strength in Children.
- 2013
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In: Medicine & Science in Sports & Exercise. - 1530-0315. ; 45:5, s. 997-1003
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Children and adolescents are encouraged to maintain a habitually active lifestyle because of the known health benefits associated with regular physical activity, but there are some reports that a high level of activity may be associated with increased fracture risk. This prospective controlled exercise intervention study in pre-pubertal children evaluated if a school-based exercise intervention could enhance growth related gains in muscle strength and muscular function without affecting fracture risk. METHODS: Fractures were registered in 417 girls and 500 boys aged 7-9 years in the intervention and in 836 age-matched girls and 872 boys. The intervention included 40 minutes/day of school physical education for two years whereas the controls achieved 60 minutes/week. In a subsample consisting of 49 girls and 80 boys in the intervention and 50 girls and 53 boys in the control group, body composition was measured by dual X-ray absorptiometry (DXA), muscle strength by isokinetic Peak Torque (PT) of the knee extensors and flexors at 60 and 180 °/seconds by a computerized dynamometer and neuromuscular performance by Vertical Jump Height (VJH). RESULTS: The rate ratio [RR (95% confidence interval)] for children in the intervention group to sustain a fracture was 1.07 (0.66, 1.68). The annual gain in knee extensor PT at 180°/seconds was significantly higher for both girls (p<0.001) and boys (p<0.01) in the intervention compared to the control group. Boys in the intervention group also had a greater annual gain in knee flexion PT at 180 °/seconds (p<0.001) and girls a greater gain in VJH (p<0.05). CONCLUSIONS: An increase in school-based physical education from 60 to 200 min/week enhanced muscle strength in pre-pubertal children without affecting fracture risk.
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| 10. |
- Löfgren, Robin
(author)
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A Theoretical Investigation of the Nitrogen-Vacancy Center in Diamond as a Single Molecule Sensor and Qubit : Charging through Explicit Electron Donors
- 2021
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Doctoral thesis (other academic/artistic)abstract
- The NV-center in diamond is one of the most well researched defects to date. Since its discovery in the 1960’s, a large body of experimental as well as theoretical work have been produced, investigating its properties and applications. The reason for the attention on this defect are its properties that are well suited for a number of applications. Some of those properties are: 1) photostable at room temperature; 2) long spin coherence time; 3) spin-flipping during the process of optical excitation and decay; 4) Optical readout of spin state. Some of the applications include qubits in quantum computers and sensors for single molecule properties. In order for the NV-center to function well, it is important to decouple its interaction with other defects in the diamond lattice or with the surface of the diamond, that could have a detrimental effect on the NV-center properties. In this work, we theoretically investigate how the NV-center properties are affected by some nearby defects. Those defects include: a nitrogen point defect in the diamond lattice, diamond surfaces, and an extended intrinsic stacking fault defect in the diamond lattice. It is the negative charge state of the NV-center that has the properties mentioned above, and therefore it is this charge state that is interesting for the applications. Here, we investigate our new theoretical method of charging the NV-center through an electron donor nitrogen in the diamond lattice. By instead charging with an explicit electron donor/acceptor, we avoid the complicated correction schemes associated with the tra-ditional theoretical method of introducing an artificial background charge density in a supercell for simulating charged defects. It can also be argued that our new method is a more physically correct method, as negatively charged NV-centers in diamond get their charge by accepting electrons from nearby nitrogens in the diamond lattice. In addition to the NV-center, we further test the method for other point defects in diamond.In this thesis, an introduction to the field is given and the current research questions are stated in chapter 1. Followed by chapters reviewing the current experimental and theoret-ical work regarding the NV-center, computational physics and density functional theory, and an overview of the software used in this work. The results presented in this thesis are obtained using density functional theory computations.Our results show that the method of charging the NV-center with a donor-nitrogen is viable for an NV-N distance of 7.5 ˚A or greater.When placing the NV-center in the vicinity to a terminated surface (F- H/O/OH- and N-terminated), its properties converge to bulk values already at 5 ˚A depth. This is great news when compared with the recent experimentally achieved distance of 1 nm, meaning that NV-centers could possibly be placed even closer to the surface without being affected. When placing the NV-center in the vicinity of an intrinsic stacking fault (ISF), our results show that the NV-center is not greatly affected down to a distance of 4.2 ˚A. However, when the NV-center is placed 3.8 ˚A or closer to the ISF, the ZPL is perturbed between 2.0 and 11.3 %. It is perturbed the most when placed inside the ISF glide plane. This is great news for the technical applications; some diamonds contain high densities of ISFs, and our results show that a NV-center can be placed really close to such an ISF without losing its sensitivity as a sensor of magnetic fields.We have also found that the excitation from the NV− ground state into donor-N+ (one-photon process) requires 2.31 eV and lead to a meta-stable NV0 and donor-N0 charge state, both of which are electron spin resonance (ESR) active and, thus, this transition could be investigated experimentally. The excitation to the neutral state can also be achieved through a two-photon process with the first step at 2.19 eV and the second step at 0.81 eV.When placing the NV-center in the vicinity to two nitrogens (one neutrally charged, and one positively charged acting as electron donor), we find that it is almost unaffected, with changes in the ZPL of 1-8 meV when the distance to the nitrogens is 9.40-12.52 ˚A. This means that a nearby nitrogen, whether it is neutral or positively charged does not affect the NV-center in a detrimental way.Our tests on charging defects through electron donors/acceptors reveals that our method also works for the following defect-donor/acceptor pairs: NV−-P+, NV−-B+, N+-B−, SiV−-N+, Be−-O+, Be2−-N+-N+.
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