| 1. |
- Kehoe, Laura, et al.
(author)
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Make EU trade with Brazil sustainable
- 2019
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Journal article (other academic/artistic)
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| 2. |
- Alaridah, Nader, et al.
(author)
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Transmission dynamics study of tuberculosis isolates with whole genome sequencing in southern Sweden
- 2019
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9
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Journal article (peer-reviewed)abstract
- Epidemiological contact tracing complemented with genotyping of clinical Mycobacterium tuberculosis isolates is important for understanding disease transmission. In Sweden, tuberculosis (TB) is mostly reported in migrant and homeless where epidemiologic contact tracing could pose a problem. This study compared epidemiologic linking with genotyping in a low burden country. Mycobacterium tuberculosis isolates (n = 93) collected at Scania University Hospital in Southern Sweden were analysed with the standard genotyping method mycobacterial interspersed repetitive units-variable number tandem repeats (MIRU-VNTR) and the results were compared with whole genome sequencing (WGS). Using a maximum of twelve single nucleotide polymorphisms (SNPs) as the upper threshold of genomic relatedness noted among hosts, we identified 18 clusters with WGS comprising 52 patients with overall pairwise genetic maximum distances ranging from zero to nine SNPs. MIRU-VNTR and WGS clustered the same isolates, although the distribution differed depending on MIRU-VNTR limitations. Both genotyping techniques identified clusters where epidemiologic linking was insufficient, although WGS had higher correlation with epidemiologic data. To summarize, WGS provided better resolution of transmission than MIRU-VNTR in a setting with low TB incidence. WGS predicted epidemiologic links better which could consolidate and correct the epidemiologically linked cases, avoiding thus false clustering.
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| 3. |
- Andersson, Erika, et al.
(author)
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A contrast variation SANS and SAXS study of soil derived dissolved organic matter, and its interactions with hematite nanoparticles
- 2023
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In: JCIS Open. ; 11
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Journal article (peer-reviewed)abstract
- Soil derived dissolved organic matter (DOM) is an important component of the carbon cycle and influences numerous biogeochemical processes, including the formation of mineral-organic associations. DOM ranges in size from small organic molecules to macromolecules and colloidal aggregates. In this study we have used small angle neutron (SANS) and X-ray (SAXS) scattering to characterize the colloidal DOM fraction from the organic layer of a boreal forest soil, and its interactions with hematite (α-Fe2O3) mineral nanoparticles. Comparison between SAXS and contrast variation SANS patterns revealed that the scattering form factor of the colloidal DOM aggregates was essentially independent of the scattering contrast, implying that the colloidal aggregates have an essentially homogeneous chemical composition, down to the nanometre length scale. Variation of the D2O/H2O ratio of the solvent yielded a SANS intensity minimum at ca. 40 vol % D2O, which was consistent with colloids composed of mainly polysaccharides. At pH 5.5 the pure hematite nanoparticles were colloidally stable in water and characterized by a ζ-potential of +25 mV and a hydrodynamic radius of ca. 70 nm. In the presence of DOM, the hematite nanoparticles lost the colloidal stability and aggregated into larger clusters, displaying a negative ζ-potential of ca. −25 mV. The charge reversal suggested that negatively charged polyanions of DOM adsorbed onto the hematite particles, possibly leading to bridging flocculation. Our results suggested that mainly low molecular weight components induced hematite aggregation because no or very limited interactions between DOM colloids and hematite were detected.
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| 4. |
- Andersson, Erika, et al.
(author)
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Generation and properties of organic colloids extracted by water from the organic horizon of a boreal forest soil
- 2023
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In: Geoderma. - : Elsevier BV. - 0016-7061. ; 432
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Journal article (peer-reviewed)abstract
- Organic colloids are an important part of dissolved organic matter (DOM) yet many of their properties remain elusive. The main aims of this study were to assess how the colloidal properties of DOM extracted with water from an organic boreal soil horizon varied with the extraction protocol, and thereby provide insight into the nature of the DOM colloids and develop a mechanistic understanding of how the colloids were generated from the parent soil aggregates. This was accomplished by systematic variations of extraction temperature (4 °C–100 °C), time, mechanical agitation, and pH, together with a combination of chemical analyses, and light and X-ray scattering. Our results agreed with the previous identification of two main colloidal DOM species, one fractal cluster and a second, smaller colloidal DOM species described as chains or coils. Fractal clusters completely dominated the colloidal DOM in extracts from our soil at room temperature and below. Colloidal coils only existed in DOM extracted above room temperature, and their amount increased significantly between 50 °C–100 °C. Moreover, the temperature variation indicated that the fractal clusters partly dissolved into colloidal coils at elevated temperatures. Mechanical agitation at 4 °C significantly increased the amount of DOM extracted, increasing the concentrations of both fractal clusters and low-molecular weight organic compounds. While the clusters were extracted from agitated and non-agitated soil suspensions, the low molecular weight organics were mainly released by agitation. Based on the experimental observations, we propose a conceptual model where parent soil aggregates contain the fractal clusters in mobile and occluded forms, and that the occluded clusters co-exist with occluded low molecular weight organics. These occluded forms may be released by mechanical forces, increasing pH and temperature. At higher temperatures, the soil aggregates and the fractal clusters start to break up, and subsequently individual colloidal coils, presumably carbohydrates, disperse in the water phase. The model explains the origin and properties of the fractal clusters that completely dominate the colloidal DOM extracted from our soil at room temperature and below.
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| 5. |
- Anrup, Roland, et al.
(author)
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Centrala universitetsvärden hotas av bolagiseringsidén
- 2013
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In: Dagens nyheter. - 1101-2447.
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Journal article (pop. science, debate, etc.)abstract
- Högskolestiftelser. Förslaget att driva svenska universitet i stiftelseform öppnar för bolagisering. Men det är ingen riktig utredning, utan en politisk pamflett utan eftertanke. Privatisering av universitet hotar både oberoendet, forskningskvaliteten och samhällsnyttan, skriver 36 forskare vid svenska högskolor och universitet.
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| 6. |
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| 7. |
- Aybay, Erdem, et al.
(author)
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Extended cleavage specificities of human granzymes A and K, two closely related enzymes with conserved but still poorly defined functions in T and NK cell-mediated immunity
- 2023
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In: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 14
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Journal article (peer-reviewed)abstract
- Granzymes A and K are two highly homologous serine proteases expressed by mammalian cytotoxic T cells (CTL) and natural killer cells (NK). Granzyme A is the most abundant of the different granzymes (gzms) expressed by these two cell types. Gzms A and K are found in all jawed vertebrates and are the most well conserved of all hematopoietic serine proteases. Their potential functions have been studied extensively for many years, however, without clear conclusions. Gzm A was for many years thought to serve as a key component in the defense against viral infection by the induction of apoptosis in virus-infected cells, similar to gzm B. However, later studies have questioned this role and instead indicated that gzm A may act as a potent inducer of inflammatory cytokines and chemokines. Gzms A and K form clearly separate branches in a phylogenetic tree indicating separate functions. Transcriptional analyses presented here demonstrate the presence of gzm A and K transcripts in both CD4+ and CD8+ T cells. To enable screening for their primary biological targets we have made a detailed analysis of their extended cleavage specificities. Phage display analysis of the cleavage specificity of the recombinant enzymes showed that both gzms A and K are strict tryptases with high selectivity for Arg over Lys in the P1 position. The major differences in the specificities of these two enzymes are located N-terminally of the cleavage site, where gzm A prefers small amino acids such as Gly in the P3 position and shows a relatively relaxed selectivity in the P2 position. In contrast, gzm K prefers large amino acids such as Phe, Tyr, and Trp in both the P2 and P3 positions and does not tolerate negatively charged residues in the P2 position. This major distinction in extended specificities is likely reflected also in preferred in vivo targets of these two enzymes. This information can now be utilized for high-precision screening of primary targets for gzms A and K in search of their highly conserved but still poorly defined functions in vertebrate immunity.
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| 8. |
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| 9. |
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| 10. |
- Betancourt, Lazaro Hiram, et al.
(author)
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The human melanoma proteome atlas-Defining the molecular pathology
- 2021
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In: Clinical and Translational Medicine. - : Wiley. - 2001-1326. ; 11:7, s. 1-20
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Journal article (peer-reviewed)abstract
- The MM500 study is an initiative to map the protein levels in malignant melanoma tumor samples, focused on in-depth histopathology coupled to proteome characterization. The protein levels and localization were determined for a broad spectrum of diverse, surgically isolated melanoma tumors originating from multiple body locations. More than 15,500 proteoforms were identified by mass spectrometry, from which chromosomal and subcellular localization was annotated within both primary and metastatic melanoma. The data generated by global proteomic experiments covered 72% of the proteins identified in the recently reported high stringency blueprint of the human proteome. This study contributes to the NIH Cancer Moonshot initiative combining detailed histopathological presentation with the molecular characterization for 505 melanoma tumor samples, localized in 26 organs from 232 patients.
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| 11. |
- Bjarnegård, Elin, 1976-, et al.
(author)
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Gender, peace and armed conflict
- 2015
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In: SIPRI Yearbook 2015. - Oxford : Oxford University Press. - 9780198737810 ; , s. 101-109
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Book chapter (peer-reviewed)
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| 12. |
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| 13. |
- Byberg, Liisa, et al.
(author)
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Reply to WB Grant
- 2017
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In: The American journal of clinical nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 106:2, s. 700-701
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Journal article (other academic/artistic)
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| 14. |
- Byberg, Liisa, et al.
(author)
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Reply to Y Mao and H Yu.
- 2017
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In: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 106:2, s. 698-699
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Journal article (other academic/artistic)
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| 15. |
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| 16. |
- Danielsson, Tatiana
(author)
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Further Investigations of Convergence Results for Homogenization Problems with Various Combinations of Scales
- 2020
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Doctoral thesis (other academic/artistic)abstract
- This thesis is based on six papers. We study the homogenization of selected parabolic problems with one or more microscopic scales in space and time, respectively. The approaches are prepared by means of certain methods, like two-scale convergence, multiscale convergence and also the evolution setting of multiscale convergence and very weak multiscale convergence. Paper I treats a linear parabolic homogenization problem with rapid spatial and temporal oscillations in perforated domains. Suitable results of two-scale convergence type are established. Paper II deals with further development of compactness results which can be used in the homogenization procedure engaging a certain limit condition. The homogenization procedure deals with a parabolic problem with a certain matching between a fast spatial and a fast temporal scale and a coefficient passing to zero that the time derivative is multiplied with. Papers III and IV are further generalizations of Paper II and investigate homogenization problems with different types of matching between the microscopic scales. Papers III and IV deal with one and two rapid scales in both space and time respectively. Paper V treats the nonlinearity of monotone parabolic problems with an arbitrary number of spatial and temporal scales by applying the perturbed test functions method together with multiscale convergence and very weak multiscale convergence adapted to the evolution setting. In Paper VI we discuss the relation between two-scale convergence and the unfolding method and potential extensions of existing results. The papers above are summarized in Chapter 4. Chapter 1 gives a brief introduction to the topic and Chapters 2 and 3 are surveys over some important previous results.
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| 17. |
- Degerman, E, et al.
(author)
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Are fish populations in temperate streams affected by crayfish? - A field survey and prospects
- 2007
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In: Environmental Biology of Fishes. - : Springer Science and Business Media LLC. - 0378-1909 .- 1573-5133. ; 78:3, s. 231-239
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Journal article (peer-reviewed)abstract
- Fish populations may be affected by predation and competition from various types of organisms, among which crayfish have been suggested as important actors. We here present results from stream surveys, suggesting that neither native noble, Astacus astacus, nor introduced signal crayfish, Pacifastacus leniusculus, necessarily affect fish population densities in temperate stream communities. Comparisons of fish densities within stream sites between years with absence and presence of crayfish showed no effect of either crayfish species. A further analysis of changes in fish densities between periods without and with crayfish in low, intermediate and high densities revealed that crayfish density did neither have an effect on fish densities. Our study is one of exceptionally few that consider the above aspects in long-term perspectives in natural systems, and we discuss that previously reported divergent results of cray. sh effects on. sh may be highly dependent on specific species and methods used, and that the effects of cray. sh on. sh populations deserve further attention to enable reliable predictions of community processes in streams.
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| 18. |
- Del Tredici, Andria L., et al.
(author)
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Identification of novel selective V-2 receptor non-peptide agonists
- 2008
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In: Biochemical Pharmacology. - : Elsevier BV. - 0006-2952 .- 1356-1839. ; 76:9, s. 1134-1141
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Journal article (peer-reviewed)abstract
- Peptides with agonist activity at the vasopressin V-2 receptor are used clinically to treat fluid homeostasis disorders such as polyuria and central diabetes insipidus. of these peptides, the most commonly used is desmopressin, which displays poor bioavailability as well as potent activity at the V-1b receptor, with possible stress-related adverse effects. Thus, there is a strong need for the development of small molecule chemistries with selective V-2 receptor agonist activity. Using the functional cell-based assay Receptor Selection and Amplification Technology (R-SAT (R)), a screening effort identified three small molecule chemotypes (AC-94544, AC-88324, and AC-110484) with selective agonist activity at the V-2 receptor. One of these compounds, AC-94544, displayed over 180-fold selectivity at the V-2 receptor compared to related vasopressin and oxytocin receptors and no activity at 28 other G protein-coupled receptors (GPCRs). All three compounds also showed partial agonist activity at the V-2 receptor in a cAMP accumulation assay. In addition, in a rat model of central diabetes insipidus, AC-94544 was able to significantly reduce urine output in a dose-dependent manner. Thus, AC-94544, AC-88324, and AC-110484 represent novel opportunities for the treatment of disorders associated with V-2 receptor agonist deficiency.
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| 19. |
- Dixon-Suen, Suzanne C, et al.
(author)
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Physical activity, sedentary time and breast cancer risk : a Mendelian randomisation study
- 2022
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In: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 56:20, s. 1157-1170
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.METHODS: We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.RESULTS: Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).CONCLUSION: Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.
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| 20. |
- Duque-Salazar, Juan Diego, et al.
(author)
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Implementing Gender Provisions : A Study of the Comprehensive Agreement on the Bangsamoro in the Philippines
- 2023
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In: International Negotiation. - : Brill Nijhoff. - 1382-340X .- 1571-8069. ; 28:2, s. 306-337
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Journal article (peer-reviewed)abstract
- While scholars on gender provisions have focused on why and how this type of peace agreement clause gets incorporated, few studies have sought to improve our understanding of the implementation process. Addressing this gap empirically, this study utilizes unique interview material to analyze the initial stages of realizing the 2014 Comprehensive Agreement on the Bangsamoro in the Philippines. The article bridges and expands on key theoretical insights based on three explanations suggested by previous research: 1) state capacity on promoting gender equality; 2) the mobilization of women's organizations; and 3) gender awareness of international actors. We find that the strategic actions of women's organizations combined with state capacity accelerated the implementation. However, their influence was dependent on whether or not the government prioritized the gender provisions, and whether international actors provided financial support to the agreement infrastructure.
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| 21. |
- Dyrrdal, Anita Verpe, et al.
(author)
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Changes in design precipitation over the Nordic-Baltic region as given by convection-permitting climate simulations
- 2023
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In: Weather and Climate Extremes. - 2212-0947. ; 42
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Journal article (peer-reviewed)abstract
- The increased risk of flooding due to global warming and subsequent heavy rainfall events in the Nordic-Baltic region, call for recommendations directed at long-term planning. One example of such recommendations are climate change allowances. These are often based on expected changes in design precipitation as given by climate model simulations, and are used as a buffer on top of current design values to avoid a future increased damage potential as a consequence of climate change. We here compute expected changes in precipitation design values, so-called climate factors (CFs), for the Nordic-Baltic region, based on 3 km convection permitting simulations from the Nordic Convection Permitting Climate Projections project. These have the advantage of explicitly resolving convection, which has been shown to be the main contributor to increased rainfall. We assess the dependence of the CFs on rainfall duration, return period, and geographical location, focusing on the summer (convective) season, short durations and the high emission scenario RCP8.5. We also compare these CFs to those computed from a non-convection permitting regional climate model ensemble. We found higher CFs for the longer return period, with only few exceptions, and distinctly higher CFs going from daily to sub-daily durations. However, the different simulations give conflicting results for very short-duration rainfall (<3 h). The huge difference in the climate sensitivity of driving GCMs dominates the magnitude of estimated return levels. Our analysis is shaped by the high computational costs of running convection permitting models, resulting in a very limited ensemble (3 members) representing a single emission scenario (RCP8.5). Therefore, we believe that combining results from convection permitting simulations with a larger ensemble (21 members) of non-convection permitting simulations adds value to the assessment of robust climate change allowances for heavy precipitation in the Nordic-Baltic region.
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| 22. |
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| 23. |
- Floudas, Dimitrios, et al.
(author)
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X-ray scattering reveals two mechanisms of cellulose microfibril degradation by filamentous fungi
- 2022
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In: Applied and Environmental Microbiology. - : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 88:17
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Journal article (peer-reviewed)abstract
- Mushroom-forming fungi (Agaricomycetes) employ enzymatic and nonenzymatic cellulose degradation mechanisms, the latter presumably relying on Fenton-generated radicals. The effects of the two mechanisms on the cellulose microfibrils structure remain poorly understood. We examined cellulose degradation caused by litter decomposers and wood decomposers, including brown-rot and white-rot fungi and one fungus with uncertain wood decay type, by combining small- and wide-angle X-ray scattering. We also examined the effects of commercial enzymes and Fenton-generated radicals on cellulose using the same method. We detected two main degradation or modification mechanisms. The first characterized the mechanism used by most fungi and resembled enzymatic cellulose degradation, causing simultaneous microfibril thinning and decreased crystalline cellulose. The second mechanism was detected in one brown-rot fungus and one litter decomposer and was characterized by patchy amorphogenesis of crystalline cellulose without substantial thinning of the fibers. This pattern did not resemble the effect of Fenton-generated radicals, suggesting a more complex mechanism is involved in the destruction of cellulose crystallinity by fungi. Furthermore, our results showed a mismatch between decay classifications and cellulose degradation patterns and that even within litter decomposers two degradation mechanisms were found, suggesting higher functional diversity under current ecological classifications of fungi.IMPORTANCE Cellulose degradation by fungi plays a fundamental role in terrestrial carbon cycling, but the mechanisms by which fungi cope with the crystallinity of cellulose are not fully understood. We used X-ray scattering to analyze how fungi, a commercial enzyme mix, and a Fenton reaction-generated radical alter the crystalline structure of cellulose. Our data revealed two mechanisms involved in crystalline cellulose degradation by fungi: one that results in the thinning of the cellulose fibers, resembling the enzymatic degradation of cellulose, and one that involves amorphogenesis of crystalline cellulose by yet-unknown pathways, resulting in a patchy-like degradation pattern. These results pave the way to a deeper understanding of cellulose degradation and the development of novel ways to utilize crystalline cellulose.
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| 24. |
- Forsberg, Erika, Docent, 1976-, et al.
(author)
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Examining Gender Inequality and Armed Conflict at the Subnational Level
- 2021
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In: Journal of Global Security Studies. - : Oxford University Press (OUP). - 2057-3170 .- 2057-3189. ; 6:2
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Journal article (peer-reviewed)abstract
- A growing body of quantitative research points to a robust relationship between gender inequality and armed conflict. In order to progress our understanding of this relationship, we make two contributions. First, we identify three potential explanations as to why gender inequality can be associated with conflict—gender inequality norms, societal capacity, and gendered socioeconomic development—and suggest an empirical strategy to gauge the explanatory leverage of each explanation. Second, we offer a more nuanced treatment of the dependent variable at the subnational level, moving beyond a dichotomized view of armed conflict to accounting for both its level and type. We test our hypotheses using district-level data on gender inequality and conflicts in India, covering the 1989–2014 period. Our findings show that the three explanations do not produce the same outcomes in the data. We argue that this speaks to the need to adjudicate between different forms of mechanisms that can connect gender inequality to conflict. Our results show support for women's status being important for understanding a society's capacity to handle conflict nonviolently. On the negative side, gendered socioeconomic developments resulting in a male surplus create conditions conducive for armed conflict, particularly in urban areas. A more surprising finding is that the gender inequality norm, in and of itself, does not appear to have a strong effect on the risk of armed conflict. This does not mean that we can disregard the explanation, but it underlines that there can be inherent problems with this commonly used argument.
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| 25. |
- Forsberg, Erika, 1976-, et al.
(author)
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Gender and conflict in Asia
- 2017
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In: Raisina Files. - New Delhi : Observer Research Foundation. - 9788186818251 ; , s. 42-49
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Book chapter (pop. science, debate, etc.)
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| 26. |
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| 27. |
- Forsberg, Erika, Docent, 1976-, et al.
(author)
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Gender Inequality and Internal Armed Conflict
- 2016
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In: Oxford Research Encyclopedia of Politics. - : Oxford University Press. ; , s. 1-18
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Journal article (peer-reviewed)abstract
- Prior research has found robust support for a relationship between gender inequality and civil war. These results all point in the same direction; countries that display lower levels of gender equality are more likely to become involved in civil conflict, and violence is likely to be even more severe, than in countries where women have a higher status. But what does gender inequality mean in this area of research? And how does research explain why we see this effect on civil war? Exploring this requires reviewing existing definitions and measurements of gender inequality, a concept that has several dimensions. Several clusters of explanations show how gender inequality could be related to civil war while more equal societies are better able to prevent violent conflict. It is clear that existing misconceptions that gender inequality primarily involves the role of women are clouding the fact that it clearly speaks to much broader societal developments which play central roles in civil war.
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| 28. |
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| 29. |
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| 30. |
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| 31. |
- Fridén, Michael, et al.
(author)
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Substitution analyses of foods with varying fat quality and the associations with all-cause mortality and impact of the FADS-1 genotype in elderly men
- 2023
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In: European Journal of Nutrition. - : Springer Berlin/Heidelberg. - 1436-6207 .- 1436-6215. ; 63, s. 145-153
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Journal article (peer-reviewed)abstract
- Purpose To investigate associations between substitutions of foods varying in fat quality and all-cause mortality in elderly Swedish men and to examine effect measure modification by a gene involved in fatty acid desaturation (rs174550 FADS1).Methods Using Cox-regression models in the ULSAM cohort (n = 1133 men aged 71), we aimed to investigate; (1) Associations between the substitution of a nutrient or food for another on all-cause mortality (primary outcome) and CVD (secondary outcome) and (2) Associations between the addition of various fat-rich foods to the habitual diet and all-cause mortality and CVD. Subgroup analyses based on the rs174550 FADS1 genotype were conducted.Results Over a mean follow-up of 11.6–13.7 years, n = 774 died and n = 494 developed CVD, respectively. No clear associations were observed for the vast majority of substitution nor addition models. Adding saturated fatty acids (SFA) on top of the habitual diet was however associated with an increased risk of mortality in men with the CT/CC-genotype [HR (95% CI) 1.44 (1.05, 1.97)]. Post-hoc analyses showed an inverse association of substituting SFA with carbohydrates [HR (95% CI) 0.79 (0.65, 0.97)], which was somewhat stronger in men with the CT/CC-genotype compared to men carrying the TT-genotype.Conclusions Few associations were observed between diet and all-cause mortality and CVD in this population. However, substituting SFA with carbohydrates was associated with lower mortality in post-hoc analyses and adding SFA to the habitual diet increased mortality in men with the CT/CC-genotype. The latter observation is novel and warrants further investigation in larger cohort studies including women.
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| 32. |
- Haitina, Tatjana, et al.
(author)
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Expression profile of the entire family of Adhesion G protein-coupled receptors in mouse and rat
- 2008
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In: BMC Neuroscience. - : BioMed Central. - 1471-2202. ; 9, s. 43-
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Journal article (peer-reviewed)abstract
- BACKGROUNDThe Adhesion G protein-coupled receptors (GPCRs) are membrane-bound receptors with long N termini. This family has 33 members in humans. Several Adhesion GPCRs are known to have important physiological functions in CNS development and immune system response mediated by large cell surface ligands. However, the majority of Adhesion GPCRs are still poorly studied orphans with unknown functions.RESULTSIn this study we performed the extensive tissue localization analysis of the entire Adhesion GPCR family in rat and mouse. By applying the quantitative real-time PCR technique we have produced comparable expression profile for each of the members in the Adhesion family. The results are compared with literature data and data from the Allen Brain Atlas project. Our results suggest that the majority of the Adhesion GPCRs are either expressed in the CNS or ubiquitously. In addition the Adhesion GPCRs from the same phylogenetic group have either predominant CNS or peripheral expression, although each of their expression profile is unique.CONCLUSIONOur findings indicate that many of Adhesion GPCRs are expressed, and most probably, have function in CNS. The related Adhesion GPCRs are well conserved in their structure and interestingly have considerable overlap in their expression profiles, suggesting similarities among the physiological roles for members within many of the phylogenetically related clusters.
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| 33. |
- Henningson, Maria, et al.
(author)
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Absence of the common IGF1 19 CA-repeat allele is more common among BRCA1 mutation carriers than among non-carriers from BRCA1 families.
- 2007
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In: Familial Cancer. - : Springer Science and Business Media LLC. - 1389-9600 .- 1573-7292. ; 6:4, s. 445-452
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Journal article (peer-reviewed)abstract
- BRCA1 mutations predispose to early-onset breast cancer. We previously reported an association between absence of the common IGF1 19 CA-repeat allele (IGF1-19/-19) and being a BRCA1 mutation carrier in young women from breast cancer high-risk families. Others have reported a four-fold risk of premenopausal breast cancer in women with a family history and the IGF1-19/-19 genotype. The aim of this study was to investigate whether the IGF1-19/-19 genotype was associated with being a BRCA1 mutation carrier among women from BRCA1 families. DNA was available from 268 women with known BRCA1 status from the South Swedish Health Care Region. IGF1 genotyping was successfully performed with fragment analysis in 211 women from 96 families. The IGF1-19/-19 genotype was significantly more common among BRCA1 mutation carriers (14.2%) than among non-carriers (4.8%), OR 3.3 (95%CI 1.11-9.78, P = 0.03) adjusted for family clustering. We confirmed our previous finding of an association between the IGF1-19/-19 genotype and BRCA1 mutation status. Since the IGF1-19/-19 genotype in combination with OC use or multiparity confers an increased risk for early onset breast cancer in high-risk women and in women from the general population, future studies are needed to elucidate the importance of the IGF1-19/-19 genotype concerning the variability in breast cancer risk among BRCA1 mutation carriers.
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| 34. |
- Henningson, Maria, et al.
(author)
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Interactions between oral contraceptive status and GSTM1 and GSTT1 deletions on insulin-like growth factor-1 (IGF-1) plasma levels in young healthy women.
- 2010
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In: Growth Hormone & Igf Research. - : Elsevier BV. - 1532-2238 .- 1096-6374. ; Dec, s. 432-437
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Insulin-like growth factor-1 (IGF-1) is essential for the pubertal growth spurt and for normal mammary gland development. IGF-1 increases premenopausal breast cancer risk. Oral contraceptives (OCs) decrease IGF-1 in most women. The endogenous estrogens and their metabolites also influence IGF-1 levels. Glutathione S-transferases (GSTs) are involved in estrogen metabolism. We aimed to study IGF-1 levels and body size in relation to GSTM1 and GSTT1 deletions, and GSTP1*1B and current oral contraceptive (OC) status. DESIGN: Questionnaires on reproductive factors and OC use were completed and blood samples were obtained during menstrual cycle day 18-23 in healthy women (≤40years) from breast cancer high-risk families. IGF-1 was analyzed with radioimmunoassay. Genetic analyses were done with PCR based methods. Initially 258 women were included. After exclusion 229 women were finally included in the analyses of IGF-1 in relation to GSTM1 and GSTT1. RESULTS: Among the 142 non-OC users, GSTM1*0/*0 or GSTT1*0/*0 alone were associated with lower IGF-1 levels while homozygous GSTM1*0/*0/GSTT1*0/*0 carriers had higher IGF-1 levels (P(interaction)=0.024). In the 87 OC users, GSTM1*0/*0 or GSTT1*0/*0 alone were associated with higher IGF-1 levels while homozygous GSTM1*0/*0/GSTT1*0/*0 carriers had lower IGF-1 levels (P(interaction)=0.010). Among all 229 women, a three-way interaction model showed an interaction between the GSTM1*0/*0/GSTT1*0/*0 genotype and OC use on IGF-1 levels (P(interaction)=0.003). GSTP1*1B was not associated with IGF-1. The GSTM1*1/GSTT1*0/*0 genotype was associated with high body weight (P=0.003) and GSTM1*0/*0/GSTT1*0/*0 was associated with early growth (P=0.003). CONCLUSION: Both OC use and GSTT1 and GSTM1 genotypes may influence IGF-1 levels. Further studies are warranted to confirm our finding and elucidate the clinical importance.
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| 35. |
- Huijser, Erika, et al.
(author)
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Serum IFNα2 measured by single-molecule array associates with systemic disease manifestations in Sjögren's syndrome
- 2022
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In: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 61:5, s. 2156-2166
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Journal article (peer-reviewed)abstract
- OBJECTIVES: Type I IFN (IFN-I) activation is a prominent feature of primary SS (pSS), SLE, and SSc. Ultrasensitive single-molecule array (Simoa) technology has facilitated the measurement of subfemtomolar concentrations of IFNs. Here, we aimed to measure IFNα2 in serum from pSS, SLE, and SSc using a Simoa immunoassay and correlate these levels to blood IFN-stimulated gene (ISG) expression and disease activity.METHODS: Serum IFNα2 was measured in patients with pSS (n = 85; n = 110), SLE (n = 24), and SSc (n = 23), and healthy controls (HC; n = 68) using an IFNα Simoa assay on a HD-X analyser. IFN-I pathway activation was additionally determined from serum by an IFN-I reporter assay and paired samples of whole blood ISG expression of IFI44, IFI44L, IFIT1, IFIT3, and MxA by RT-PCR or MxA-ELISA.RESULTS: Serum IFNα2 levels were elevated in pSS (median=61.3 fg/mL) compared to HC (median ≤5 fg/mL; p < 0.001) and SSc (median=11.6 fg/mL; p = 0.043), lower compared to SLE (median=313.5 fg/mL; p = 0.068), and positively correlated with blood ISG expression (r = 0.66-0.94; p < 0.001). Comparable to MxA-ELISA (AUC=0.93), IFNα2 measurement using Simoa identified pSS with high ISG expression (AUC=0.90) with 80-93% specificity and 71-84% sensitivity. Blinded validation in an independent pSS cohort yielded a comparable accuracy. Multiple regression indicated independent associations of autoantibodies, IgG, HCQ treatment, cutaneous disease and history of extraglandular manifestations with serum IFNα2 concentrations in pSS.CONCLUSION: Thus, Simoa serum IFNα2 reflects blood ISG expression in pSS, SLE, and SSc. In light of IFN-targeting treatments, Simoa could potentially be applied for patient stratification or retrospective analysis of historical cohorts.
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| 36. |
- Isaksson, Johan, et al.
(author)
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Predictors of long-term survival and recurrence patterns after definitive chemoradiotherapy in stage III NSCLC – a multicenter cohort study from Mid Sweden
-
Other publication (other academic/artistic)abstract
- Background: Stage III NSCLC is heterogeneous but often recurs despite intensive treatment with curative intent. Clinical tools to predict the risk and pattern of recurrence and long-term survival in individual patients are largely lacking. Methods: NSCLC stage III patients (N=193) treated 2009-2018 with definitive, curatively intended chemoradiotherapy (CRT, 60Gy+) were retrospectively identified from three healthcare regions in Mid Sweden. Outcome variables included overall survival (OS), progression-free survival (PFS) and recurrence patterns. Results: Median follow-up of patients alive was 52 months. 1, 2 and 5-year OS was 80%, 63% and 34% with a mOS of 32 months. Pre-treatment serum inflammatory markers were associated with inferior OS, including leukocyte count > 10 (HR 1.58, 95% CI 1.08-2.31, p=0.018) and CRP > 5 (HR 1.81, 95% CI 1.16-2.83, p=0.009). CRP remained independently associated with OS in multivariable analysis, HR 1.67 (1.05-2.65, p=0.029). No other pre-treatment variable was significantly associated with OS. Progressive disease (PD) was documented in 65% of patients after a median time of 9.5 months, 96% within 3 years from CRT, and was typically either distant or locoregional (12% mixed). Distant PD developed earlier (6.3 months) than locoregional PD (11.5 months; p=0.052). N3 disease (OR 2.7, 95% CI 1.2-6.3,; p=0.022) and presence of driver mutations (OR 4.6, 95% CI 1.5-14.0; p=0.0076) increased the risk of distant PD, while ≥2 concurrent chemotherapy courses was protective of locoregional PD (OR 0.38, 9% CI 0.1-1.0; p=0.049). Brain metastases were the first indication of PD in 22 patients (12%) and were in all cases isolated without synchronous extracranial PD. A post-CRT 18F-FDG-PET SUVmax of ≥7 was associated with a shorter time to PD (HR 0.41, 95% CI 0.21-0.79, p=0.008). Conclusions: The study reinforces the prognostic role of systemic inflammation in stage III NSCLC and provides clinically useful indicators of relapse pattern as a basis for rational disease monitoring following CRT.
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| 37. |
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| 38. |
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| 39. |
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| 40. |
- Karlsson, Mikael, et al.
(author)
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Ability to predict resting energy expenditure with six equations compared to indirect calorimetry in octogenarian men
- 2017
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In: Experimental Gerontology. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0531-5565 .- 1873-6815. ; 92, s. 52-55
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Journal article (peer-reviewed)abstract
- The accuracy of predictive equations for calculating resting energy expenditure (REE) in elderly people has been questioned. Aging is associated with progressive declines in REE, which partly is explained by loss of fat free mass (FFM). Against this background we aimed to identify the most accurate predictive equation for REE in octogenarian men, taking body composition into account and using indirect calorimetry as reference value. REE was measured in 22 men (mean age 82.6 +/- 0.3 years) and compared with six predictive equations: two based on FFM and four based on body weight, height and/or age. FFM was derived from Dual-energy X-ray absorptiometry analyses. Spearman's rank correlations showed a moderate to high positive monotonic correlation (r = 0.62 to 0.79) between measured and calculated REE (all p < 0.005).The mean calculated REE was significantly different from measured REE for all equations except Mifflin-St Jeor. A calculated REE within 10% of measured REE was considered acceptable and the equations of Mifflin-St Jeor, WHO and Harris-Benedict captured 64%, 50% and 45% of the participant, respectively. The Mifflin-St Jeor equation had the lowest root mean square error (138 kcal), followed by the equation by Harris-Benedict (189 kcal) and WHO (220 kcal). The equations from Luhrmann, Henry and Cunningham predicted REE rather poorly in our study subjects, with e.g. <40% of the individuals within 10% of measured REE. Our results indicate that the Mifflin-St Jeor equation (using FFM) is the most accurate equation estimating REE in these octogenarian men. Harris-Benedict or WHO equations are potential alternatives if information on FFM is unavailable, although their accuracy on an individual level is limited.
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| 41. |
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| 42. |
- Lehmann, Fredrik, 1976, et al.
(author)
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Design, parallel synthesis and SAR of novel urotensin II receptor agonists
- 2007
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In: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 42, s. 276-285
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Journal article (peer-reviewed)abstract
- A 30-membered library of amides based on the potent urotensin II (UII) receptor agonist FL104, has been synthesized from ten different carboxylic acids and three amines. A synthetic protocol producing the amides in 47-98% yield has been developed in which the purification involved only extractions and in a few cases filtration through an ion-exchange resin. It was found that 5 mg of starting material was enough to obtain reproducible results and excellent purities. Thus, the procedure is estimated to be transferable to fully automated systems. The synthesized compounds were evaluated for their UII receptor agonistic activities using a cell-based assay (R-SAT). The most active compounds were the 4-trifluoromethylcinnamic amides of 1-(4-chlorophenyl)-3-dimethylamino-propylamine and 1-(2-naphthyl)-3-dimethylamino-propylamine, both showed EC50 values of 130 nM. © 2006 Elsevier Masson SAS. All rights reserved.
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| 43. |
- Lehmann, Fredrik, 1976, et al.
(author)
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Isochromanone-based urotensin-II receptor agonists.
- 2005
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In: Bioorganic & medicinal chemistry. - : Elsevier BV. - 0968-0896. ; 13:8, s. 3057-68
-
Journal article (peer-reviewed)abstract
- A series of analogues of the selective non-peptide urotensin II (UII) receptor agonist 3-(4-chlorophenyl)-3-(2-dimethylaminoethyl)-isochroman-1-one (AC-7954, 1) was synthesized and evaluated for UII agonist activity using a functional cell-based assay. The introduction of a methyl group in the 4-position resulted in a complete loss of activity, whereas substituents in the aromatic rings were beneficial. Sterically demanding amino groups were also detrimental to the activity. Several potent agonists were identified, six compounds being equally or more potent than 1. The most potent compound in the series was the 6,7-dimethyl analogue of 1 (16, pEC50 6.87). The racemate of 16 was resolved into the pure enantiomers using preparative straight phase HPLC. It was shown that the potency resides in the (+)-enantiomer (pEC50 7.11). The synthesized compounds seem to be selective for the UII receptor as no activities were observed at the closely related SSTR3 and 5 receptors.
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| 44. |
- Lehmann, Fredrik, 1976, et al.
(author)
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Novel and potent small-molecule urotensin II receptor agonists
- 2009
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In: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896. ; 17:13, s. 4657-4665
-
Journal article (peer-reviewed)abstract
- A series of analogs of the non-peptidic urotensin II receptor agonist N-[1-(4-chlorophenyl)-3-(dimethylamino)propyl]-4-phenylbenzamide (FL104) has been synthesized and evaluated pharmacologically. The enantiomers of the two most potent racemic analogues were obtained from the corresponding diastereomeric mandelic amides. In agreement with previously observed SAR, most of the agonist potency resided in the (S) enantiomers. The most potent UII receptor agonist in the new series was (S)-N-[3-dimethylamino-1-(2-naphthyl)propyl]-4-(4-chlorophenyl)benzamide (EC50 = 23 nM at the urotensin II receptor).
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| 45. |
- Lehmann, Fredrik, 1976, et al.
(author)
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Novel potent and efficacious nonpeptidic urotensin II receptor agonists
- 2006
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 49, s. 2232-2240
-
Journal article (peer-reviewed)abstract
- Six different series of nonpeptidic urotensin II receptor agonists have been synthesized and evaluated for their agonistic activity in a cell-based assay (R-SAT). The compounds are ring-opened analogues of the isochromanone-based agonist AC-7954 with different functionalities constituting the linker between the two aromatic ring moieties. Several of the compounds are highly potent and efficacious, with N-[1-(4-chlorophenyl)-3-(dimethylamino)- propyl]-4-phenylbenzamide oxalate (5d) being the most potent. The pure enantiomers of 5d were obtained from the corresponding diastereomeric amides. It was shown by a combination of X-ray crystallography and chemical correlation that the activity resides in the S-enantiomer of 5d (pEC50 7.49). © 2006 American Chemical Society.
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| 46. |
- Lehmann, Fredrik, 1976, et al.
(author)
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Optimization of isochromanone based urotensin II receptor agonists.
- 2010
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In: Bioorganic & medicinal chemistry. - : Elsevier BV. - 1464-3391 .- 0968-0896. ; 18:13, s. 4844-4854
-
Journal article (peer-reviewed)abstract
- A series of novel isochromanone based urotensin II receptor agonists have been synthesized and evaluated for their activity using a functional cell based assay (R-SAT). Several potent and efficacious derivatives were identified with 3-(3,4-dichlorophenyl)-6,7-dimethyl-3-(2-dimethylaminoethyl)isochroman-1-one (28) being the most potent compound showing an EC(50)-value of 51nM, thereby being the most potent compound so far within the isochromanone series. In addition, two other heterocyclic systems (isochromanes and tetrahydroisoquinolinones) were investigated and these derivatives were found to be both potent and efficacious. The activity of the isochromane derivatives implies that the carbonyl group of the isochromanone is not necessary for activity. Furthermore it was found that the geometry of the heterocycles was more important for receptor interaction than the composition of the heteroatoms present.
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| 47. |
- Lindgård, Jan, et al.
(author)
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Nordic Europe
- 2017
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In: Alkali-aggregate reaction in concrete. - : Taylor & Francis. - 9781315708959 - 9781138027565 ; , s. 277-320, s. 185-211
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Book chapter (other academic/artistic)
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| 48. |
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| 49. |
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| 50. |
- Martin, Andrew, et al.
(author)
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Measures to improve angiotensin receptor blocker prescribing efficiency in the UK : findings and implications
- 2014
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In: Journal of Comparative Effectiveness Research. - : Becaris Publishing Limited. - 2042-6305 .- 2042-6313. ; 3:1, s. 41-51
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Journal article (peer-reviewed)abstract
- Background: Generic losartan provides an opportunity to enhance angiotensin receptor blocker (ARB) prescribing efficiency, with all ARBs essentially being similar. Initially, there was limited activity in NHS Bury (UK). This changed in March 2011 with therapeutic switching and other measures encouraging the prescribing of losartan following generics to enhance its utilization versus patented ARBs. Aim: This study aims to assess the impact of multiple measures on losartan utilization, its price and total ARB expenditure. Methods: An interrupted time series analysis was performed. Utilization was measured as prescription items dispensed, typically 28 days. Results: No immediate change in losartan utilization was observed following generics. This changed after the multiple initiatives with losartan accounting for 65% of all single ARB items dispensed by the study end. ARB expenditure was 59% below prestudy levels by the study end, which was helped by a 92% reduction in expenditure per item for losartan. Annual net savings from the program were estimated at just under GB 290,000 pound, which is over eight-times the cost of implementation. Conclusion: Multiple measures can enhance prescribing efficiency. Health authorities cannot rely on a spillover' effect from other classes in order to affect changes in physician prescribing habits.
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