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1.	Moberg, Christina, et al. (författare) De unga gör helt rätt när de stämmer staten 2022 Ingår i: Aftonbladet. - 1103-9000. Tidskriftsartikel (populärvet., debatt m.m.)abstract 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
2.	Bonaca, MP, et al. (författare) Long-term use of ticagrelor in patients with prior myocardial infarction 2015 Ingår i: The New England journal of medicine. - 1533-4406. ; 372:19, s. 1791-1800 Tidskriftsartikel (refereegranskat)
3.	Forshell, Linus Plym, 1977-, et al. (författare) The direct Myc target Pim3 cooperates with other Pim kinases in supporting viability of Myc-induced B-cell lymphomas 2011 Ingår i: Oncotarget. - Albany, N.Y. : Impact Journals. - 1949-2553. ; 2:6, s. 448-460 Tidskriftsartikel (refereegranskat)abstract The Pim kinases are weak oncogenes. However, when co-expressed with a strong oncogene, such as c-Myc, Pim kinases potentiate the oncogenic effect resulting in an acceleration of tumorigenesis. In this study we show that the least studied Pim kinase, Pim-3, is encoded by a gene directly regulated by c-Myc via binding to one of the conserved E-boxes within the Pim3 gene. Accordingly, lymphomas arising in Myc-transgenic mice and Burkitt lymphoma cell lines exhibit elevated levels of Pim-3. Interestingly, inhibition of Pim kinases by a novel pan-Pim kinase inhibitor, Pimi, in Myc-induced lymphoma results in cell death that appears independent of caspases. The data indicate that Pim kinase inhibition could be a viable treatment strategy in certain human lymphomas that rely on Pim-3 kinase expression.
4.	Hoellein, Alexander, et al. (författare) Myc-induced SUMOylation is a therapeutic vulnerability for B-cell lymphoma. 2014 Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 124:13, s. 2081-90 Tidskriftsartikel (refereegranskat)abstract Myc oncogenic transcription factors (c-Myc, N-Myc, and L-Myc) coordinate the control of cell growth, division, and metabolism. In cancer, Myc overexpression is often associated with aggressive disease, which is in part due to the destruction of select targets by the ubiquitin-proteasome system (eg, SCF(Skp2)-directed destruction of the Cdk inhibitor p27(Kip1)). We reasoned that Myc would also regulate SUMOylation, a related means of posttranslational modification of proteins, and that this circuit would play essential roles in Myc-dependent tumorigenesis. Here, we report marked increases in the expression of genes that encode regulators and components of the SUMOylation machinery in mouse and human Myc-driven lymphomas, resulting in hyper-SUMOylation in these tumors. Further, inhibition of SUMOylation by genetic means disables Myc-induced proliferation, triggering G2/M cell-cycle arrest, polyploidy, and apoptosis. Using genetically defined cell models and conditional expression systems, this response was shown to be Myc specific. Finally, in vivo loss-of-function and pharmacologic studies demonstrated that inhibition of SUMOylation provokes rapid regression of Myc-driven lymphoma. Thus, targeting SUMOylation represents an attractive therapeutic option for lymphomas with MYC involvement.
5.	Höglund, Andreas, 1980-, et al. (författare) Therapeutic implications for the induced levels of Chk1 in Myc- expressing cancer cells 2011 Ingår i: Clinical Cancer Research. - Philadelphia : Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 17:22, s. 7067-7079 Tidskriftsartikel (refereegranskat)abstract Purpose: The transcription factor c-Myc (or "Myc") is a master regulator of pathways driving cell growth and proliferation. MYC is deregulated in many human cancers, making its downstream target genes attractive candidates for drug development. We report the unexpected finding that B-cell lymphomas from mice and patients exhibit a striking correlation between high levels of Myc and checkpoint kinase 1 (Chk1). Experimental Design: By in vitro cell biology studies as well as preclinical studies using a genetically engineered mouse model, we evaluated the role of Chk1 in Myc-overexpressing cells. Results: We show that Myc indirectly induces Chek1 transcript and protein expression, independently of DNA damage response proteins such as ATM and p53. Importantly, we show that inhibition of Chk1, by either RNA interference or a novel highly selective small molecule inhibitor, results in caspase-dependent apoptosis that affects Myc-overexpressing cells in both in vitro and in vivo mouse models of B-cell lymphoma. Conclusion: Our data suggest that Chk1 inhibitors should be further evaluated as potential drugs against Myc-driven malignancies such as certain B-cell lymphoma/leukemia, neuroblastoma, and some breast and lung cancers. Clin Cancer Res; 17(22); 7067-79. (C) 2011 AACR.
6.	Abelius, Martina, 1980- (författare) Immunological interactions between mother and child during pregnancy in relation to the development of allergic diseases in the offspring 2014 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Background: Pregnancy and allergic disease have both been postulated as T-helper 2 (Th2) phenomena. Thus, the increased propensity of allergic mothers to mount Th2-responses might generate favourable effects on the maintenance of pregnancy, but might also be unfavorable, as fetal exposure to a strong Th2 environment could influence the immune development in the offspring to a Th2-like phenotype, favouring IgE production and possibly allergy development later in life. The influence of the intrauterine environment on the immunity and allergy development in the offspring needs to be further investigated.Aim: The aim of this thesis was to explore the Th1/Th2 balance in allergic and non-allergic women during pregnancy and its influence on the shaping of the Th1/Th2 profile in the neonate and the development of allergic diseases in the offspring.Material and methods: The study group included 20 women with and 36 women without allergic symptoms followed during pregnancy (gestational week 10-12, 15-16, 25, 35, 39) and 2 and 12 months postpartum, and their children followed from birth to 6 years of age. The circulating Th1-like chemokines CXCL9, CXCL10, CXCL11, Th2-like chemokines CCL17, CCL18 and CCL22, and the allergen-induced secretion of interleukin-4 (IL-4), IL-5, IL-10, IL-13, Interferon-γ (IFN-γ), CXCL10 and CCL17 were measured by Luminex and ELISA. The allergen-specific and total IgE levels were quantified using ImmunoCAP Technology. mRNA expression of Th1-, Th2-, Treg- and Th17-associated genes were measured by PCR arrays and real-time PCR.Results: We found that sensitised women with allergic symptoms had increased total IgE levels and birch- and cat-induced IL-5, IL-13 and CCL17 responses during pregnancy as compared with postpartum. The non-sensitised women without allergic symptoms had elevated cat-induced IL-5 and IL-13 responses and lower birch- and cat-induced IFN-γ during pregnancy, but similar IgE levels as compared with postpartum.Maternal total IgE levels during and after pregnancy correlated with cord blood (CB) IgE and CCL22 levels (regardless of maternal allergy status). Circulating CXCL11, CCL18 and CCL22 levels during pregnancy and postpartum correlated with the corresponding chemokine levels in the offspring at various time points during childhood. Maternal IL-5 expression in peripheral blood mononuclear cells (PBMC) was associated with neonatal Galectin-1, and placental p35 expression was negatively associated with neonatal Tbx21 expression. Increased mRNA expression of CCL22 in cord blood mononuclear cells (CBMC), and increased CCL17 and CCL22 levels in CB were observed in children later developing allergic symptoms and sensitisation as compared with children who did not. Development of allergic symptoms and sensitisation were associated with increased total IgE, CCL17, CCL18 and CCL22 levels during childhood.Conclusions: Maternal allergy was associated with a pronounced Th2 deviation during pregnancy, shown as increased total IgE levels and birch- and cat-induced IL-5, IL-13 and CCL17 responses during pregnancy, possibly exposing their fetuses to a particular strong Th2 environment during gestation.Correlations were shown between the maternal immunity during pregnancy and the offspring’s immunity at birth and later during childhood, indicating an interplay between the maternal and fetal immunity.Allergy development during the first 6 years of life was associated with a marked Th2 deviation at birth and a delayed down-regulation of this Th2-skewed immunity during childhood.
7.	Abelius, Martina S, et al. (författare) Gene expression in placenta, peripheral and cord blood mononuclear cells from allergic and non-allergic women 2014 Annan publikation (övrigt vetenskapligt/konstnärligt)abstract Background: The influence of maternal allergy on the development of immune responses and allergy in the offspring is not understood.Objective: To investigate (i) if maternal allergy influences the gene expression locally in placenta, systemically in peripheral blood mononuclear cells (PBMC) and fetally in cord blood mononuclear cells (CBMC), (ii) if the gene expression in the placenta and PBMC influences the gene expression in CBMC and (iii) how the gene expression at birth relates to allergy development during childhood.Methods: A real-time PCR array was used to quantify forty immune regulatory genes in placenta, PBMC (gestational week 39) and in CBMC from 7 allergic and 12 non-allergic women and their offspring. Furthermore, quantitative real-time PCR was used to measure mRNA expression of Tbx21, GATA-3, Foxp3, RORC and CCL22 in CBMC, selected based on present PCR array results and previous protein findings in cord blood, in 13 children who developed and 11 children who did not develop allergy during childhood.Results: The gene expression profile in the placenta revealed a T-helper (Th) 2-/anti-inflammatory environment as compared with gene expression systemically, in PBMC. Maternal allergy was associated with increased expression of p35 in PBMC and CBMC and p40 in placenta. Placental p35 expression correlated with fetal Tbx21 expression (Rho=-0.88, p<0.001) and maternal IL-5 expression in PBMC with fetal Galectin-1 (Rho=0.91, p<0.001) expression. Allergy development in the children was preceded by high mRNA expression of the Th2-associated chemokine CCL22 at birth.Conclusion and clinical relevance: Gene expression locally and systemically during pregnancy influenced the offspring’s gene expression at birth, indicating an interplay between maternal and fetal immunity. Children developing allergy during childhood had an increased expression of the Th2-associated chemokine CCL22 at birth, indicating a Th2 skewing before disease onset. Maternal allergy was not associated with a Th2-dominance in placenta, PBMC or CBMC.
8.	Abelius, Martina S, et al. (författare) High cord blood levels of the T-helper 2-associated chemokines CCL17 and CCL22 precede allergy development during the first 6 years of life 2011 Ingår i: Pediatric Research. - 0031-3998 .- 1530-0447. ; 70:5, s. 495-500 Tidskriftsartikel (refereegranskat)abstract Exposure to a strong T-helper 2 (Th2)-like environment during fetal development may promote allergy development. Increased cord blood (CB) levels of the Th2-associated chemokine CCL22 were associated with allergy development during the first 2 y of life. The aim of the present study was to determine whether CB Th1- and Th2-associated chemokine levels are associated with allergy development during the first 6 y of life, allowing assessment of respiratory allergic symptoms usually developing in this period. The CB levels of cytokines, chemokines, and total IgE were determined in 56 children of 20 women with allergic symptoms and 36 women without allergic symptoms. Total IgE and allergen-specific IgE antibody levels were quantified at 6, 12, 24 mo, and 6 y of age. Increased CB CCL22 levels were associated with development of allergic sensitization and asthma and increased CCL17 levels with development of allergic symptoms, including asthma. Sensitized children with allergic symptoms showed higher CB CCL17 and CCL22 levels and higher ratios between these Th2-associated chemokines and the Th1-associated chemokine CXCL10 than nonsensitized children without allergic symptoms. A pronounced Th2 deviation at birth, reflected by increased CB CCL17 and CCL22 levels, and increased CCL22/CXCL10 and CCL17/CXCL10 ratios might promote allergy development later in life.
9.	Abelius, Martina S, et al. (författare) Th2-like chemokine levels are increased in allergic children and influenced by maternal immunity during pregnancy 2014 Ingår i: Pediatric Allergy and Immunology. - : John Wiley & Sons. - 0905-6157 .- 1399-3038. ; 25:4, s. 387-393 Tidskriftsartikel (refereegranskat)abstract Background: The influence of the intra-uterine environment on the immunity and allergy development in the offspring is unclear. We aimed to investigate (i) whether the pregnancy magnifies the Th2 immunity in allergic and non-allergic women, (ii) whether the maternal chemokine levels during pregnancy influenced the offspring’s chemokine levels during childhood and (iii) the relationship between circulating Th1/Th2-associated chemokines and allergy in mothers and children.Methods: The Th1-associated chemokines CXCL9, CXCL10, CXCL11, and the Th2- associated chemokines CCL17, CCL18 and CCL22 were quantified by Luminex and ELISA in 20 women with and 36 women without allergic symptoms at gestational week (gw) 10–12, 15–16, 25, 35, 39 and 2 and 12 months post-partum and in their children at birth, 6, 12, 24 months and 6 yr of age. Total IgE levels were measured using ImmunoCAP Technology.Results: The levels of the Th2-like chemokines were not magnified by pregnancy. Instead decreased levels were shown during pregnancy (irrespectively of maternal allergy status) as compared to post-partum. In the whole group, the Th1-like chemokine levels were higher at gw 39 than during the first and second trimester and post-partum. Maternal CXCL11, CCL18 and CCL22 levels during and after pregnancy correlated with the corresponding chemokines in the offspring during childhood. Increased CCL22 and decreased CXCL10 levels in the children were associated with sensitisation and increased CCL17 levels with allergic symptoms during childhood. Maternal chemokine levels were not associated with maternal allergic disease.Conclusions: Allergic symptoms and sensitisation were associated with decreased Th1-and increased Th2-associated chemokine levels during childhood, indicating a Th2 shift in the allergic children, possibly influenced by the maternal immunity during pregnancy.
10.	Abelius, Martina S, et al. (författare) The Placental Immune Milieu is Characterized by a Th2- and Anti-Inflammatory Transcription Profile, Regardless of Maternal Allergy, and Associates with Neonatal Immunity 2015 Ingår i: American Journal of Reproductive Immunology. - : Wiley-Blackwell. - 1046-7408 .- 1600-0897. ; 73:5, s. 445-459 Tidskriftsartikel (refereegranskat)abstract PROBLEM: How maternal allergy affects the systemic and local immunological environment during pregnancy and the immune development of the offspring is unclear.METHOD OF STUDY: Expression of 40 genes was quantified by PCR arrays in placenta, peripheral blood mononuclear cells (PBMC), and cord blood mononuclear cells (CBMC) from 7 allergic and 12 non-allergic women and their offspring.RESULTS: Placental gene expression was dominated by a Th2-/anti-inflammatory profile, irrespectively of maternal allergy, as compared to gene expression in PBMC. p35 expression in placenta correlated with fetal Tbx21 (ρ = -0.88, P < 0.001) and IL-5 expression in PBMC with fetal galectin1 (ρ = 0.91, P < 0.001). Increased expression of Th2-associated CCL22 in CBMC preceded allergy development.CONCLUSIONS: Gene expression locally and systemically during pregnancy was partly associated with the offspring's gene expression, possibly indicating that the immunological milieu is important for fetal immune development. Maternal allergy was not associated with an enhanced Th2 immunity in placenta or PBMC, while a marked prenatal Th2 skewing, shown as increased CCL22 mRNA expression, might contribute to postnatal allergy development.
11.	Andréasson, Hanna, et al. (författare) Coding mtDNA analysis for increased forensic discrimination power using Pyrosequencing technology Annan publikation (övrigt vetenskapligt/konstnärligt)
12.	Andréasson, Hanna, et al. (författare) Forensic mitochondrial coding region analysis for increased discrimination using pyrosequencing technology 2007 Ingår i: Forensic Science International. - : Elsevier BV. - 1872-4973 .- 1878-0326. ; 1:1, s. 35-43 Tidskriftsartikel (refereegranskat)abstract Analysis of mitochondrial DNA (mtDNA) is very useful when nuclear DNA analysis fails due to degradation or insufficient amounts of DNA in forensic analysis. However, mtDNA analysis has a lower discrimination power compared to what can be obtained by nuclear DNA (nDNA) analysis, potentially resulting in multiple individuals showing identical mtDNA types in the HVI/HVII region. In this study, the increase in discrimination by analysis of mitochondrial coding regions has been evaluated for identical or similar HVI/HVII sequences. A pyrosequencing-based system for coding region analysis, comprising 17 pyrosequencing reactions performed on 15 PCR fragments, was utilised. This assay was evaluated in 135 samples, resulting in an average read length of 81 nucleotides in the pyrosequencing analysis. In the sample set, a total of 52 coding region SNPs were identified, of which 18 were singletons. In a group of 60 samples with 0 or 1 control region difference from the revised Cambridge reference sequence (rCRS), only 12 samples could not be resolved by at least two differences using the pyrosequencing assay. Thus, the use of this pyrosequencing-based coding region assay has the potential to substantially increase the discriminatory power of mtDNA analysis.
13.	Andréasson, Hanna, et al. (författare) Nuclear and mitochondrial DNA quantification of various forensic materials 2006 Ingår i: Forensic Science International. - : Elsevier BV. - 0379-0738 .- 1872-6283. ; 164:1, s. 56-64 Tidskriftsartikel (refereegranskat)abstract Due to the different types and quality of forensic evidence materials, their DNA content can vary substantially, and particularly low quantities can impact the results in an identification analysis. In this study, the quantity of mitochondrial and nuclear DNA was determined in a variety of materials using a previously described real-time PCR method. DNA quantification in the roots and distal sections of plucked and shed head hairs revealed large variations in DNA content particularly between the root and the shaft of plucked hairs. Also large intra- and inter-individual variations were found among hairs. In additions DNA content was estimated in samples collected from fingerprints and accessories. The quantification of DNA on various items also displayed large variations, with some materials containing large amounts of nuclear DNA while no detectable nuclear DNA and only limited amounts of mitochondrial DNA were seen in others. Using this sensitive real-time PCR quantification assay, a better understanding was obtained regarding DNA content and variation in commonly analysed forensic evidence materials and this may guide the forensic scientist as to the best molecular biology approach for analysing various forensic evidence materials.
14.	Andréasson, Hanna, et al. (författare) Quantification of mtDNA mixtures in forensic evidence material using pyrosequencing 2006 Ingår i: International journal of legal medicine. - : Springer Science and Business Media LLC. - 0937-9827 .- 1437-1596. ; 120:6, s. 383-390 Tidskriftsartikel (refereegranskat)abstract Analysis of mtDNA variation using Sanger sequencing does not allow accurate quantification of the components of mtDNA mixtures. An alternative method to determine the specific mixture ratios in samples displaying heteroplasmy, consisting of DNA contributions from several individuals, or containing contamination would therefore be valuable. A novel quantification system for mtDNA mixture analysis has been developed based on pyrosequencing technology, in which the linear relationship between incorporated nucleotides and released light allows quantification of the components of a sample. Within five polymerase chain reaction fragments, seven variable positions in the mtDNA control and coding region were evaluated using this quantification analysis. For all single nucleotide polymorphisms quantified in this study, a linear relationship was observed between the measured and expected mixture ratios. This mtDNA quantification assay is an easy to use, fast and accurate quantification system, with the ability to resolve and interpret major and minor mtDNA components in forensic mixture samples.
15.	Aspholm-Hurtig, Marina, et al. (författare) Functional adaptation of BabA, the H. pylori ABO blood group antigen binding adhesin. 2004 Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 305:5683, s. 519-22 Tidskriftsartikel (refereegranskat)abstract Adherence by Helicobacter pylori increases the risk of gastric disease. Here, we report that more than 95% of strains that bind fucosylated blood group antigen bind A, B, and O antigens (generalists), whereas 60% of adherent South American Amerindian strains bind blood group O antigens best (specialists). This specialization coincides with the unique predominance of blood group O in these Amerindians. Strains differed about 1500-fold in binding affinities, and diversifying selection was evident in babA sequences. We propose that cycles of selection for increased and decreased bacterial adherence contribute to babA diversity and that these cycles have led to gradual replacement of generalist binding by specialist binding in blood group O-dominant human populations.
16.	Backström, Tobias, et al. (författare) Anaesthesia and handling stress effects on pigmentation and monoamines in Arctic charr 2017 Ingår i: Environmental Biology of Fishes. - : Springer. - 0378-1909 .- 1573-5133. ; 100:5, s. 471-480 Tidskriftsartikel (refereegranskat)abstract Stress responsiveness differs between individuals and is often categorized into different stress coping styles. Using these stress coping styles for selection in fish farming could be beneficial, since stress is one main factor affecting welfare. In Arctic charr (Salvelinus alpinus) carotenoid pigmentation is associated with stress responsiveness and stress coping styles. Thus this could be an important tool to use for selection of stress resilient charr. However, anaesthetics seem to affect carotenoid pigmentation, and it would be better if the method for selection could be implemented during normal maintenance, which usually includes anaesthetics. Therefore, this study investigated how the use of anaesthetics affected carotenoid pigmentation, i.e. number of spots, over time compared to no-anaesthetic treatment. Additionally, the stress indicators monoamines and glucocorticoids were investigated. The results indicate that the anaesthetic MS-222 affects number of spots on the right side. This anaesthetic also increased dopaminergic activity in the telencephalon. Both brain dopaminergic and serotonergic activity was associated with spottiness. Further, behaviour during anaesthetization was associated with spots on the left side, but not the right side. Repetition of the same treatment seemed to affect spot numbers on the right side. In conclusion, this study shows that inducing stress in charr affects the carotenoid spots. Thus, it is possible to use anaesthetics when evaluating spottiness although careful planning is needed.
17.	Backström, Tobias, et al. (författare) Dominance and stress signalling of carotenoid pigmentation in Arctic charr (Salvelinus alpinus): Lateralization effects? 2015 Ingår i: Physiology and Behavior. - : Elsevier BV. - 0031-9384 .- 1873-507X. ; 138, s. 52-57 Tidskriftsartikel (refereegranskat)abstract Social conflicts are usually solved by agonistic interactions where animals use cues to signal dominance or subordinance. Pigmentation change is a common cue used for signalling. In our study, the involvement of carotenoid-based pigmentation in signalling was investigated in juvenile Arctic charr (Salvelinus alpinus). Size-matched pairs were analysed for pigmentation both before and after being tested for competitive ability. We found that dominant individuals had fewer carotenoid-based spots on the right and left sides as well as lower plasma cortisol levels compared to subordinate individuals. Further, the number of spots on both sides was positively associated with plasma cortisol levels. These results indicate that carotenoid-based pigmentation in Arctic charr signals dominance and stress coping style. Further, it also appears as if carotenoid-based pigmentation is lateralized in Arctic charr, and that the right side signals aggression and dominance whereas the left side signals stress responsiveness. (C) 2014 Elsevier Inc. All rights reserved.
18.	Backström, Tobias, et al. (författare) Social stress effects on pigmentation and monoamines in Arctic charr 2015 Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 291, s. 103-107 Tidskriftsartikel (refereegranskat)abstract Pigmentation often signals status and in general melanin-based pigmentation is indicative of aggression and stress resilience in vertebrates. This is evident in the salmonids Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss) where more melanin spotted individuals are more stress resilient. However, in the salmonid Arctic charr (Salvelinus alpinus) it seems as if it is carotenoid-based pigmentation that signals aggression and stress resilience. In our study, social stress effects on carotenoid-based spots, and behavioural and physiological stress responses were investigated. Socially stressed individuals have more spots, and behavioural stress responses were associated with spots. Some of the results concerning physiological stress responses, such as plasma cortisol levels and monoaminergic activity, are associated with spottiness. Further, the earlier proposed lateralization of spots, with left side connected to stress responsiveness and right side to aggression, is to some extent validated although not conclusively. In conclusion, this study provides further evidence that more stressed charr have more carotenoid spots, and for the first time monoaminergic activity is shown to be connected with carotenoid pigmentation.
19.	Backström, Tobias, et al. (författare) The effect of anesthetics on carotenoid pigmentation and behavior in Arctic char (Salvelinus alpinus) 2015 Ingår i: Journal of Veterinary Behavior: Clinical Applications and Research. - : Elsevier BV. - 1558-7878 .- 1878-7517. ; 10, s. 179-184 Tidskriftsartikel (refereegranskat)abstract Status of individual animals is often shown in pigmentation. For instance, stress responsiveness is associated with melanin-based pigmentation in vertebrates in general. This pattern is evident in Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss), with melanin-based spots indicating stress coping style. Arctic char (Salvelinus alpinus) differ from other salmonids in pigmentation but have an association between carotenoid-based pigmentation and stress coping style. These pigmentation differences could be used as a fast and simple tool for improving breeding programs. However, the procedure for photographing individuals is stressful. Therefore, we wanted to investigate if 3 common inhalation anesthetics could be used to reduce the stress involved in the procedure compared to a no-anesthetics group. Behavior was also monitored during the anesthetization. All 3 anesthetics (Aquacalm, Benzocaine, and MS-222) differed in pigmentation compared to the no-anesthetics group by having a higher number of spots. In the anesthetic treatments as well as the no-anesthetics group, the fish had elevated plasma cortisol levels. In fact, the no-anesthetics group had higher cortisol than treated fish. This was probably because of procedural differences such as time affecting the stress response. Furthermore, in a long-term experiment, all fish survived and had similar condition factors 1 week after photographing as before. Therefore, the method for photographing Arctic char is deemed safe and could be used as a tool for estimating stress coping style, but careful planning is needed for experiments using it
20.	Berg, Sandra, 1984, et al. (författare) Knowledge transfer within and across organizational boundaries: A case study in the construction industry 2012 Ingår i: ARCOM 28th Annual Conference, Edinburgh, 3-5 September 2012. ; 1 Konferensbidrag (refereegranskat)abstract Knowledge transfer is essential for an organization to be competitive and successful. However, as projects are temporary, knowledge is often bound to the individuals in projects rather than to the core organizations. The main research question for this article is: How can collaboration be used in order to transfer knowledge from one project to another within an organization or with other organizations within a project? To do this, a theoretical framework of recent literature concerning knowledge management and transfer is used, as well as a case study about an urban development organization working with a rather unique collaboration structure in order to maximize the knowledge transfer from and between different actors. Our method of research has been interviews with a divisional manager and two project managers at an urban development organization. Results from our case study indicate that in the planning phase, knowledge transfer includes collecting feedback and information as well as using a central knowledge platform. During the production phase, face-to-face communication is the most important form of knowledge transfer. After each project, evaluation is essential to collect the experience of collaboration and identify planning errors. Our findings also show that most knowledge transfer occurs at an informal level. The study concludes that several factors affect knowledge transfer in a construction organization. The most essential are the media in which knowledge is transferred and the way information is stored. Taking all factors into consideration, an organization with a decentralized structure and an open and broad-minded culture enables successful knowledge transfer.
21.	Beye, Martin, et al. (författare) Chemical Bond Activation Observed with an X-ray Laser 2016 Ingår i: The Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 7:18, s. 3647-3651 Tidskriftsartikel (refereegranskat)abstract The concept of bonding and antibonding orbitals is fundamental in chemistry. The population of those orbitals and the energetic difference between the two reflect the strength of the bonding interaction. Weakening the bond is expected to reduce this energetic splitting, but the transient character of bond-activation has so far prohibited direct experimental access. Here we apply time-resolved soft X-ray spectroscopy at a free electron laser to directly observe the decreased bonding antibonding splitting following bond-activation using an ultrashort optical laser pulse.
22.	Björk, Martina, et al. (författare) Dido til Eneas: en Ovidius-översättning av Anna Maria Lenngren 2017 Ingår i: Humanitas: festskrift till Arne Jönsson. - 9789170612442 Bokkapitel (refereegranskat)
23.	Bus, Magdalena M., et al. (författare) Analysis of Mitochondrial DNA from a Burned, Ninhydrin-Treated Paper Towel 2016 Ingår i: Journal of Forensic Sciences. - : Wiley. - 0022-1198 .- 1556-4029. ; 61:3, s. 828-832 Tidskriftsartikel (refereegranskat)abstract Contact-based evidence is likely to have limited quantities of DNA and may yield mixed profiles due to preexisting or contaminating DNA. In a recent arson investigation, a paper towel was collected and used as circumstantial evidence. The paper towel was partially burned and was likely set on fire with flammable liquid. As part of the investigation, the paper towel was treated with ninhydrin to visualize fingerprint evidence. Initial DNA analysis of two swabs was negative for short tandem repeat (STR) markers and revealed a mixture of mitochondrial DNA (mtDNA). Analysis of 13 additional cuttings yielded four more mixed profiles, but also two samples with a common single-source profile. The single-source mtDNA profile matched that of the primary suspect in the case. Thus, even if initial mtDNA analysis yields a mixed profile, a sampling strategy involving multiple locations can improve the chance of obtaining valuable single-source mtDNA profiles from compromised evidence in criminal casework.
24.	Chaitanya, Lakshmi, et al. (författare) Collaborative EDNAP exercise on the IrisPlex system for DNA based prediction of human eye colour 2014 Ingår i: Forensic Science International. - : Elsevier. - 1872-4973 .- 1878-0326. ; 11, s. 241-251 Tidskriftsartikel (refereegranskat)abstract The IrisPlex system is a DNA-based test system for the prediction of human eye colour from biological samples and consists of a single forensically validated multiplex genotyping assay together with a statistical prediction model that is based on genotypes and phenotypes from thousands of individuals. IrisPlex predicts blue and brown human eye colour with, on average, >94% precision accuracy using six of the currently most eye colour informative single nucleotide polymorphisms (HERC2 rs12913832, OCA2 rs1800407, SLC24A4 rs12896399, SLC45A2 (MATP) rs16891982, TYR rs1393350, and IRF4 rs12203592) according to a previous study, while the accuracy in predicting non-blue and non-brown eye colours is considerably lower. In an effort to vigorously assess the IrisPlex system at the international level, testing was performed by 21 laboratories in the context of a collaborative exercise divided into three tasks and organised by the European DNA Profiling (EDNAP) Group of the International Society of Forensic Genetics (ISFG). Task 1 involved the assessment of 10 blood and saliva samples provided on FTA cards by the organising laboratory together with eye colour phenotypes; 99.4% of the genotypes were correctly reported and 99% of the eye colour phenotypes were correctly predicted. Task 2 involved the assessment of 5 DNA samples extracted by the host laboratory from simulated casework samples, artificially degraded, and provided to the participants in varying DNA concentrations. For this task, 98.7% of the genotypes were correctly determined and 96.2% of eye colour phenotypes were correctly inferred. For Tasks 1 and 2 together, 99.2% (1875) of the 1890 genotypes were correctly generated and of the 15 (0.8%) incorrect genotype calls, only 2 (0.1%) resulted in incorrect eye colour phenotypes. The voluntary Task 3 involved participants choosing their own test subjects for IrisPlex genotyping and eye colour phenotype inference, while eye photographs were provided to the organising laboratory and judged; 96% of the eye colour phenotypes were inferred correctly across 100 samples and 19 laboratories. The high success rates in genotyping and eye colour phenotyping clearly demonstrate the reproducibility and the robustness of the IrisPlex assay as well as the accuracy of the IrisPlex model to predict blue and brown eye colour from DNA. Additionally, this study demonstrates the ease with which the IrisPlex system is implementable and applicable across forensic laboratories around the world with varying pre-existing experiences.
25.	Chiriacò, Martina, et al. (författare) Female sex and angiotensin-converting enzyme (ace) insertion/deletion polymorphism amplify the effects of adiposity on blood pressure 2022 Ingår i: Hypertension. - 0194-911X. ; 79:1, s. 36-46 Tidskriftsartikel (refereegranskat)abstract The pathophysiological link between adiposity and blood pressure is not completely understood, and evidence suggests an influence of sex and genetic determinants. We aimed to identify the relationship between adiposity and blood pressure, independent of a robust set of lifestyle and metabolic factors, and to examine the modulating role of sex and Angiotensin-Converting Enzyme (ACE) insertion/deletion (I/D) polymorphisms. In the Relationship Between Insulin Sensitivity and Cardiovascular Disease (RISC) study cohort, 1211 normotensive individuals, aged 30 to 60 years and followed-up after 3.3 years, were characterized for lifestyle and metabolic factors, body composition, and ACE genotype. Body mass index (BMI) and waist circumference (WC) were independently associated with mean arterial pressure, with a stronger relationship in women than men (BMI: R=0.40 versus 0.30; WC: R=0.40 versus 0.30, both P<0.01) and in individuals with the ID and II ACE genotypes in both sexes (P<0.01). The associations of BMI and WC with mean arterial pressure were independent of age, sex, lifestyle, and metabolic variables (standardized regression coefficient=0.17 and 0.18 for BMI and WC, respectively) and showed a significant interaction with the ACE genotype only in women (P=0.03). A 5 cm larger WC at baseline increased the risk of developing hypertension at follow-up only in women (odds ratio, 1.56 [95% CI, 1.15-2.10], P=0.004) and in II genotype carriers (odds ratio, 1.87 [95% CI, 1.09-3.20], P=0.023). The hypertensive effect of adiposity is more pronounced in women and in people carrying the II variant of the ACE genotype, a marker of salt sensitivity.
26.	den Hollander, Jürgen, et al. (författare) Aurora kinases A and B are Myc targets essential for maintenance of the malignant state Annan publikation (övrigt vetenskapligt/konstnärligt)
27.	Diesen, Elias, et al. (författare) Ultrafast Adsorbate Excitation Probed with Subpicosecond-Resolution X-Ray Absorption Spectroscopy 2021 Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 127:1 Tidskriftsartikel (refereegranskat)abstract We use a pump-probe scheme to measure the time evolution of the C K-edge x-ray absorption spectrum from CO/Ru(0001) after excitation by an ultrashort high-intensity optical laser pulse. Because of the short duration of the x-ray probe pulse and precise control of the pulse delay, the excitation-induced dynamics during the first picosecond after the pump can be resolved with unprecedented time resolution. By comparing with density functional theory spectrum calculations, we find high excitation of the internal stretch and frustrated rotation modes occurring within 200 fs of laser excitation, as well as thermalization of the system in the picosecond regime. The ∼100 fs initial excitation of these CO vibrational modes is not readily rationalized by traditional theories of nonadiabatic coupling of adsorbates to metal surfaces, e.g., electronic frictions based on first order electron-phonon coupling or transient population of adsorbate resonances. We suggest that coupling of the adsorbate to nonthermalized electron-hole pairs is responsible for the ultrafast initial excitation of the modes.
28.	Divne, Anna-Maria, et al. (författare) Forensic casework analysis using the HVI/HVII mtDNA linear array assay. 2005 Ingår i: Journal of Forensic Sciences. - 0022-1198 .- 1556-4029. ; 50:3, s. 548-554 Tidskriftsartikel (refereegranskat)abstract The mitochondrial hypervariable regions I and II have proven to be a useful target for analysis of forensic materials, in which the amount of DNA is limited or highly degraded. Conventional mitochondrial DNA (mtDNA) sequencing can be time-consuming and expensive, limitations that can be minimized using a faster and less expensive typing assay. We have evaluated the exclusion capacity of the linear array mtDNA HVI/HVII region-sequence typing assay (Roche Applied Science) in 16 forensic cases comprising 90 samples. Using the HVI/HVII mtDNA linear array, 56% of the samples were excluded and thus less than half of the samples require further sequencing due to a match or inconclusive results. Of all the samples that were excluded by sequence analysis, 79% could be excluded using the HVI/HVII linear array alone. Using the HVI/HVII mtDNA linear array assay, we demonstrate the potential to decrease sequencing efforts substantially and thereby reduce the cost and the turn-around time in casework analysis.
29.	Dören, Martina, et al. (författare) Effects of specific post-menopausal hormone therapies on bone mineral density in post-menopausal women: a meta-analysis. 2003 Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 18:8, s. 1737-1746 Tidskriftsartikel (refereegranskat)
30.	Edlund, Hanna, et al. (författare) DNA extraction and analysis of skeletal remains Annan publikation (övrigt vetenskapligt/konstnärligt)abstract Skeletal remains are often exposed to diverse conditions that affect the biological material in different ways. As a consequence, DNA in aged skeletal remains is often present in minute amounts, highly degraded and contains inhibitors that can affect the amplification reaction. These issues together with the high risk of contamination with exogenous DNA make molecular analysis of old remains a challenging task. Efficient methods for the extraction of DNA that maximise the yield and simultaneously remove inhibitors as well as contaminants would therefore be desirable, both for forensic investigations and for the study of ancient DNA analysis. This study describes the evaluation of three protocols for extraction of DNA from aged skeletal remains. Whole and pulverised samples from a skull and ulna that had been buried for approximately 70 years were treated with bleach and different concentrations of EDTA and proteinase K. The DNA was thereafter extracted using a salting out procedure based on the Wizard® Genomic Purification system. The efficiency of the three protocols was estimated by mtDNA quantification, which revealed that the extracts contained between 0 and 14 110 copies/100mg bone. In general, the ulna bone resulted in higher yields of mtDNA compared to the skull bone. The most efficient extraction protocol was the one involving the highest concentration of EDTA. Soaking the bone samples in commercial bleach prior to extraction was found to be a useful method of eliminating contaminants while retaining sufficient DNA for analysis. Moreover, a maternal relationship was investigated for the remains analysed in this study.
31.	Fava, Cristiano, et al. (författare) Association between adducin-1 G460W variant and blood pressure in Swedes is dependent on interaction with body mass index and gender. 2007 Ingår i: American Journal of Hypertension. - : Oxford University Press (OUP). - 1941-7225 .- 0895-7061. ; 20:9, s. 981-989 Tidskriftsartikel (refereegranskat)abstract Background: The W allele of the G460W polymorphism in the adducin-1 gene has been occasionally associated with increased blood pressure (BP). The aim of this study was to test whether the G460W variant is associated with BP levels and BP progression rate and whether G460W associations with BP are affected by sex, body mass index (BMI), or age. Methods: The G460W polymorphism was genotyped in the population-based Malmo Diet and Cancer-cardiovascular arm (MDC-CVA; n = 6103), of whom 53% had also been examined 11 +/- 4.4 years earlier in the Malmo Preventive Project (MPP). Results: Among subjects without antihypertensive treatment (AHT) in the MDC-CVA (n = 5009), there was no difference between carriers (38%) and noncarriers (62%) of the W allele in systolic BP (139.2 +/- 18.2 v 139.2 +/- 18.5 mm Hg; P = .99) or diastolic BP (85.9 +/- 9.1 v 86.1 +/- 9.2 mm Hg; P = .49). In subjects free from AHT in the MPP and MDC (n = 2637) there was no difference between carriers (38%) and noncarriers (62%) in progression of systolic BP (2.0 +/- 2.5 v 2.0 +/- 2.7 mm Hg/year; P = .45) or diastolic BP (0.59 +/- 1.6 v 0.56 +/- 1.5 mm Hg/year; P = .66) from MPP to MDC. At MDC-CVA BP was influenced by interaction between the G460W and BMI (P = .02 for systolic BP and P = .002 for diastolic BP) and by interaction between G460W and sex (P = .03 for systolic BP and P = .02 for diastolic BP), a result further confirmed by stratified analysis showing that female carriers of the W allele belonging to the upper tertile of BMI had increased systolic BP (146.1 +/- 18.6 v 141.2 +/- 18.6 mm Hg; P < .001), diastolic BP (88.7 +/- 8.7 v 86.1 +/- 8.7 mm Hg; P < .001), and prevalence of hypertension (72.5% v 61.8 %; P = .001). Conclusions: Our data suggest that the G460W polymorphism influences BP when BMI and sex are taken into account.
32.	Fava, Cristiano, et al. (författare) Novel mutations in the SLC12A3 gene causing Gitelman's syndrome in Swedes 2007 Ingår i: DNA Sequence. - : Informa UK Limited. - 1029-2365 .- 1042-5179. ; 18:5, s. 395-399 Tidskriftsartikel (refereegranskat)abstract PURPOSE: Gitelman's syndrome (GS) is an inherited autosomal recessive disorder due to loss of function mutations in the SLC12A3 gene encoding the Na-Cl co-transporter (NCCT), the target of thiazide diuretics. The defective function of the NCCT, which normally is expressed in the apical membrane of the distal convolute tubule in the kidney, leads to mild hypotension, hypokalemia, hyperreninemic hyperaldosteronism, mild metabolic alkalosis, hypomagnesemia and hypocalciuria. Up to now, more than 100 mutations of the SLC12A3 gene have been described in GS patients. METHODS: We have collected 30 patients from Sweden with a clinical diagnosis of GS and undertaken a mutation screening by SSCP and successive sequencing of the 26 exons and intronic boundaries. Both mutations were identified in most (n = 28, 93%) and at least one mutation was identified in all patients. RESULTS: We found 22 different mutations evenly distributed throughout the gene, 11 of which have not been described previously. The new variants include 8 missense mutations (Glu68Lys, His69Asn, Argl45His, Vall53Met, Gly230Asp, Gly342Ala, Val677Leu and Gly867Ser), 1 insertion (c.834_835insG on exon 6) and 2 splice-site mutations (c.2667 + lT>G substitution in splicing donor site after exon 22, c.1569-1G>A substitution in the splicing acceptor site before exon 13). CONCLUSION: In Swedish patients with the clinical features of GS, disease-causing mutations in the SLC12A3 gene were identified in most patients. The spectrum of GS mutations is wide making full mutation screening of the SLC12A3 gene necessary to confirm the diagnosis.
33.	Fava, Cristiano, et al. (författare) Prediction of Blood Pressure Changes Over Time and Incidence of Hypertension by a Genetic Risk Score in Swedes. 2012 Ingår i: Hypertension. - 1524-4563. Tidskriftsartikel (refereegranskat)abstract Recent Genome-Wide Association Studies (GWAS) have pinpointed different single nucleotide polymorphisms consistently associated with blood pressure (BP) and hypertension prevalence. However, little data exist regarding single nucleotide polymorphisms predicting BP variation over time and hypertension incidence. The aim of this study was to confirm the association of a genetic risk score (GRS), based on 29 independent single nucleotide polymorphisms, with cross-sectional BP and hypertension prevalence and to challenge its prediction of BP change over time and hypertension incidence in >17 000 middle-aged Swedes participating in a prospective study, the Malmö Preventive Project, investigated at baseline and over a 23-year average period of follow-up. The GRS was associated with higher systolic and diastolic BP values both at baseline (β±SEM, 0.968±0.102 mm Hg and 0.585±0.064 mm Hg; P<1E-19 for both) and at reinvestigation (β±SEM, 1.333±0.161 mm Hg and 0.724±0.086 mm Hg; P<1E-15 for both) and with increased hypertension prevalence (odds ratio [95% CI], 1.192 [1.140-1.245] and 1.144 [1.107-1.183]; P<1E-15 for both). The GRS was positively associated with change (Δ) in BP (β±SEM, 0.033±0.008 mm Hg/y and 0.023±0.004 mm Hg/y; P<1E-04 for both) and hypertension incidence (odds ratio [95% CI], 1.110 [1.065-1.156]; P=6.7 E-07), independently from traditional risk factors. The relative weight of the GRS was lower in magnitude than obesity or prehypertension, but comparable with diabetes mellitus or a positive family history of hypertension. A C-statistics analysis does not show any improvement in the prediction of incident hypertension on top of traditional risk factors. Our data from a large cohort study show that a GRS is independently associated with BP increase and incidence of hypertension.
34.	Fava, Cristiano, et al. (författare) Serine/threonine kinase 39 is a candidate gene for primary hypertension especially in women: results from two cohort studies in Swedes. 2011 Ingår i: Journal of Hypertension. - 1473-5598. ; 29, s. 484-491 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: As recently pinpointed by a genome-wide association study the serine/threonine kinase 39 (STK39) is a candidate gene for hypertension. This kinase is strongly implicated in sodium reabsorption by the kidney through its modulating effect on furosemide-sensitive and thiazide-sensitive channels. The aim of our study was to test the effects of the STK39 rs35929607A>G polymorphism on blood pressure (BP) levels and the prevalence and incidence of hypertension in middle-aged Swedes participating in two urban-based surveys in Malmö (Sweden). METHODS: The rs35929607A>G polymorphism was genotyped in 5634 participants included in the cardiovascular cohort of the 'Malmö Diet and Cancer-cardiovascular arm' (MDC-CVA) study and successively in 17 894 participants of the 'Malmö Preventive Project' (MPP) both at baseline and at reinvestigation after a mean of 23 years. The effect of the same single nucleotide polymorphism on salt sensitivity was tested in 39 participants of the Salt Reduction to Avoid Hypertension study. RESULTS: Both before and after adjustment for covariates, the functional rs35929607A>G polymorphism was associated with higher SBP and DBP values in the MDC-CVA, but not in the MPP. In both surveys, the polymorphism was associated with hypertension prevalence; after adjustment using the autosomal-dominant model, the odds ratio for hypertension ranged between 1.077 (MPP at baseline) and 1.151 (MDC-CVA) with P-value less than 0.05. After stratification for sex, the results remained statistically significant in women, but not in men. Carriers of the G-allele displayed an increase in salt sensitivity. CONCLUSION: Our results from two large cohort studies support previous evidence about the association of the STK39 rs35929607A>G variant with hypertension, especially in women. If further confirmed in successive studies, owing to its pivotal role in sodium reabsorption at the renal tubule level, STK39 might prove to be a suitable target for antihypertensive therapy. The greater effect of the STK39 rs35929607A>G polymorphism in women with respect to men deserves further investigation.
35.	Fava, Cristiano, et al. (författare) Subjects heterozygous for genetic loss of function of the thiazide-sensitive cotransporter have reduced blood pressure 2008 Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 17:3, s. 413-418 Tidskriftsartikel (refereegranskat)abstract Gitelmans syndrome (GS) is an inherited recessive disorder caused by homozygous or compound heterozygous loss of function mutations of the NaCl cotransporter (NCCT) gene encoding the kidney-expressed NCCT, the pharmacological target of thiazide diuretics. An observational study estimated the prevalence of GS to 19/1 000 000, in Sweden, suggesting that similar to 1% of the population carries one mutant NCCT allele. As the phenotype of GS patients, who always carry two mutant alleles, is indistinguishable from that seen in patients treated with high-dose thiazide diuretics, we aimed at investigating whether subjects carrying one mutated NCCT allele have a phenotype resembling that of treatment with low-dose thiazide diuretics. We screened first-degree relatives of 18 of our patients with an established clinical end genetic diagnosis of GS for NCCT loss of function mutations and identified 35 healthy subjects carrying one mutant allele (GS-heterozygotes). Each GS-heterozygote was assigned a healthy control subject matched for age, BMI and sex. GS-heterozygotes had markedly lower blood pressure (systolic 103.3 +/- 16.4 versus 123.2 +/- 19.4 mmHg; diastolic 62.5 +/- 10.5 versus 73.1 +/- 9.4 mmHg; P < 0.001) than controls. There was no significant difference between the groups either in plasma concentration or urinary excretion rate of electrolytes, however, GS-heterozygotes had higher fasting plasma glucose concentration. Similar to patients being treated with low-dose thiazide diuretics, GS-heterozygotes have markedly lower blood pressure and slightly higher fasting plasma glucose compared with control subjects. Our findings suggest that GS-heterozygotes, the prevalence of which can be estimated to 1%, are partially protected from hypertension through partial genetic loss of function of the NCCT. However, as our study had a case-control design, it is important to underline that any potential effects on population blood pressure and risk of future cardiovascular disease need to be examined in prospective and population-based studies.
36.	Fava, Cristiano, et al. (författare) The functional variant of the CLC-Kb channel T481S is not associated with blood pressure or hypertension in Swedes. 2007 Ingår i: Journal of Hypertension. - 1473-5598. ; 25:1, s. 111-116 Tidskriftsartikel (refereegranskat)abstract Objective A common threonine481serine polymorphism (T481S) has been shown in vitro to strongly activate the chloride channel Kb (CLC-Kb) expressed in the kidney, and the 481S allele has been associated with human hypertension. The study aim was to evaluate the association of the T481 S polymorphism with blood pressure (BP) levels and the BP progression rate in Swedes. Design and methods The cardiovascular cohort of the Malmo Diet and Cancer (MDC) study is a population surveyed in 1991-1996 (n = 6103, DNA available on n = 6055), 53% of whom had also been examined 11 +/- 4.4 years earlier in the Malmo preventive Project (MPP) Hypertension was defined as having BP above 140/90 mmHg or being on antihypertensive therapy (AHT). Carriers of one or two copies of the 481S allele were compared with T481T homozygotes (noncarriers). Results Among individuals without AHT in the MIX study (n = 4988) there was no difference between carriers (n = 1164, 23%) and noricarriers (n = 3824, 77%) in systolic BP (139.3 +/- 8.3 vs 139.2 +/- 8.3 mmHg, P=0.82) or diastolic BP (86.0 +/- 9.1 vs 86.0 +/- 9.2 mmHg, P = 0.95). In subjects free from AHT at the Ill and Ill studies (n = 2627) there was no difference between carriers (n = 607, 23%) and noricarriers (n = 2020, 77%) in progression of systolic BP (2.1 +/- 2.6 vs 2.0 +/- 2.8 mmHg/year, P = 0.72) or diastolic BP (0.57 +/- 1.4 vs 0.58 +/- 1.6 mmHg/year, P = 0.85) from Ill to Ill Multivariate analysis gave no support of interaction between the CLC-Kb 481S polymorphism, gender, age or body mass index regarding their effect on BP. Conclusion Our data do not support a role of the CLC-Kb T481S polymorphism in BP regulation in Swedes.
37.	Fava, Cristiano, et al. (författare) The V433M Variant of the CYP4F2 Is Associated With Ischemic Stroke in Male Swedes Beyond Its Effect on Blood Pressure. 2008 Ingår i: Hypertension. - 1524-4563. ; 52, s. 373-380 Tidskriftsartikel (refereegranskat)abstract Cytochrome (CYP) 4A11 and CYP4F2 are responsible for renal production of 20-hydroxyeicosatetraenoic acid, a vasoconstrictor and natriuretic substance. The CYP4A11 F434S and CYP4F2 V433M polymorphisms reduce 20-hydroxyeicosatetraenoic acid production in vitro. The aim of the present study was to evaluate the effect of these polymorphisms on blood pressure (BP) levels, hypertension prevalence, and risk of incident cardiovascular events in middle-aged Swedes. The polymorphisms were genotyped in the cardiovascular cohort of the Malmö Diet and Cancer Study. The incidence of cardiovascular events (coronary events, n=276; ischemic stroke, n=199) was monitored over 10 years of follow-up. The analysis of BP levels was performed twice: either excluding or including subjects under antihypertensive treatment. In the whole population, CYP4A11 S434S homozygotes had higher systolic BP, both crude and adjusted for the number of antihypertensive drugs, and higher prevalence of hypertension with respect to F434 carriers. Male, but not female, CYP4F2 M433 carriers had significantly higher crude and adjusted systolic and diastolic BPs and a trend toward higher hypertension prevalence (P=0.06) with respect to V433V homozygotes. After adjustment for major cardiovascular risk factors, the hazard ratio for incident ischemic stroke in male CYP4F2 M433 carriers was significantly higher with respect to V433V homozygotes (hazard ratio: 1.69; 95% CI: 1.10 to 2.60) even when baseline BP levels and hypertension prevalence were included in the Cox proportional hazard model. A common CYP4F2 V433M polymorphism might increase the risk of incident ischemic stroke in male subjects only partially through its elevating effect on BP. Additional studies are needed to confirm these data.
38.	Flannick, Jason, et al. (författare) Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls 2017 Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4 Tidskriftsartikel (refereegranskat)abstract To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
39.	Food security in the High North : contemporary challenges across the circumpolar region 2021 Samlingsverk (redaktörskap) (refereegranskat)abstract This book explores the challenges facing food security, sustainability, sover-eignty, and supply chains in the Arctic, with a specific focus on Indigenous Peoples.Offering multidisciplinary insights with a particular focus on populations in the European High North region, the book highlights the importance of accessible and sustainable traditional foods for the dietary needs of local and Indigenous Peoples. It focuses on foods and natural products that are unique to this region and considers how they play a significant role towards food security and sovereignty. The book captures the tremendous com-plexity facing populations here as they strive to maintain sustainable food systems – both subsistent and commercial – and regain sovereignty over tra-ditional food production policies. A range of issues are explored from food contamination risks, due to increasing human activities in the region, such as mining, to changing livelihoods and gender roles in the maintenance of traditional food security and sovereignty. The book also considers process-ing methods that combine indigenous and traditional knowledge to convert the traditional foods, which are harvested or hunted, into local foods.This book offers a broader understanding of food security and sovereignty, and will be of interest to academics, scholars, and policy makers working in food studies, geography and environmental studies, agricultural studies, so-ciology, anthropology, political science, health studies, and biology.
40.	Food security in the high north : contemporary challenges across the circumpolar region 2021 Samlingsverk (redaktörskap) (refereegranskat)abstract This book explores the challenges facing food security, sustainability, sovereignty, and supply chains in the Arctic, with a specific focus on Indigenous Peoples. Offering multidisciplinary insights and with a particular focus on populations in the European High North region, the book highlights the importance of accessible and sustainable traditional foods for the dietary needs of local and Indigenous Peoples. It focuses on foods and natural products that are unique to this region and considers how they play a significant role towards food security and sovereignty. The book captures the tremendous complexity facing populations here as they strive to maintain sustainable food systems - both subsistent and commercial - and regain sovereignty over traditional food production policies. A range of issues are explored including food contamination risks, due to increasing human activities in the region, such as mining, to changing livelihoods and gender roles in the maintenance of traditional food security and sovereignty. The book also considers processing methods that combine indigenous and traditional knowledge to convert the traditional foods, that are harvested and hunted, into local foods. This book offers a broader understanding of food security and sovereignty and will be of interest to academics, scholars and policy makers working in food studies; geography and environmental studies; agricultural studies; sociology; anthropology; political science; health studies and biology.
41.	Fuchsberger, Christian, et al. (författare) The genetic architecture of type 2 diabetes 2016 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47 Tidskriftsartikel (refereegranskat)abstract The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
42.	Gaulton, Kyle J, et al. (författare) Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci. 2015 Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415 Tidskriftsartikel (refereegranskat)abstract We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
43.	Girardi, Benedetta, et al. (författare) Selective Monovalent Galectin-8 Ligands Based on 3-Lactoylgalactoside 2022 Ingår i: ChemMedChem. - : Wiley. - 1860-7179 .- 1860-7187. ; 17:3 Tidskriftsartikel (refereegranskat)abstract Galectin-8 has gained attention as a potential new pharmacological target for the treatment of various diseases, including cancer, inflammation, and disorders associated with bone mass reduction. To that end, new molecular probes are needed in order to better understand its role and its functions. Herein we aimed to improve the affinity and target selectivity of a recently published galectin-8 ligand, 3-O-[1-carboxyethyl]-β-d-galactopyranoside, by introducing modifications at positions 1 and 3 of the galactose. Affinity data measured by fluorescence polarization show that the most potent compound reached a KD of 12 μM. Furthermore, reasonable selectivity versus other galectins was achieved, making the highlighted compound a promising lead for the development of new selective and potent ligands for galectin-8 as molecular probes to examine the protein's role in cell-based and in vivo studies.
44.	Good, James A. D., et al. (författare) Thiazolino 2-pyridone amide isosteres as inhibitors of Chlamydia trachomatis infectivity 2017 Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 60:22, s. 9393-9399 Tidskriftsartikel (refereegranskat)abstract Chlamydia trachomatis is a global health burden due to its prevalence as a sexually transmitted disease and as the causative agent of the eye infection trachoma. We recently discovered 3-amido thiazolino 2-pyridones which attenuated C. trachomatis infectivity without affecting host cell or commensal bacteria viability. We present here the synthesis and evaluation of nonhydrolyzable amide isosteres based on this class, leading to highly potent 1,2,3-triazole based infectivity inhibitors (EC50 ≤ 20 nM).
45.	Herman, Maria Dolores, et al. (författare) Structures of BIR domains from human NAIP and cIAP2 2009 Ingår i: Acta Crystallographica. Section F. - 1744-3091 .- 1744-3091. ; 65, s. 1091-1096 Tidskriftsartikel (refereegranskat)abstract The inhibitor of apoptosis (IAP) family of proteins contains key modulators of apoptosis and inflammation that interact with caspases through baculovirus IAP-repeat (BIR) domains. Overexpression of IAP proteins frequently occurs in cancer cells, thus counteracting the activated apoptotic program. The IAP proteins have therefore emerged as promising targets for cancer therapy. In this work, X-ray crystallography was used to determine the first structures of BIR domains from human NAIP and cIAP2. Both structures harbour an N-terminal tetrapeptide in the conserved peptide-binding groove. The structures reveal that these two proteins bind the tetrapeptides in a similar mode as do other BIR domains. Detailed interactions are described for the P1'-P4' side chains of the peptide, providing a structural basis for peptide-specific recognition. An arginine side chain in the P3' position reveals favourable interactions with its hydrophobic moiety in the binding pocket, while hydrophobic residues in the P2' and P4' pockets make similar interactions to those seen in other BIR domain-peptide complexes. The structures also reveal how a serine in the P1' position is accommodated in the binding pockets of NAIP and cIAP2. In addition to shedding light on the specificity determinants of these two proteins, the structures should now also provide a framework for future structure-based work targeting these proteins.
46.	Herman, Maria Dolores, et al. (författare) The first crystal structure of BIR domains from Human NAIP and cIAP Tidskriftsartikel (refereegranskat)
47.	Hossain, Kamrul, et al. (författare) Introduction : conceptualizing food (in)security in the High North 2021 Ingår i: Food Security in the High North. - Abingdon : Routledge. - 9781138370067 - 9781003057758 ; , s. 1-12 Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract This introduction presents an overview of the key concepts discussed in the subsequent chapters of this book. The book uses various other concepts, such as food resilience and traditional and local knowledge in food practices and in traditional food systems. It defines food resilience as ‘capacity over time of a food system and its units at multiple levels, to provide sufficient, appropriate and accessible food to all, in the face of various and even unforeseen disturbances’. The book analyses issues related to Indigenous Peoples, livelihood practices, and traditional knowledge in the context of food production, consumption, and diversity. It explores the value of stockfish for strengthening the local food system and the role of stockfish in enhancing local food security. The book investigate the potential of Indigenous knowledge-based traditional pasture management and a rotational grazing system. It highlights the food insecurity of reindeer herders after the 1986 Chernobyl nuclear accident.
48.	Huhtamäki, Martina, et al. (författare) Frasformade instruktioner med uppföljningar under personlig träning 2019 Ingår i: Språk och stil. - : Uppsala University. - 1101-1165 .- 2002-4010. ; 29, s. 9-40 Tidskriftsartikel (refereegranskat)abstract Personal training is a new form of institutional interaction that has not been considerably studied as regards language. Still, alongside embodied interaction, language is central in this activity. In this paper, phrasal utterances are studied as a resource for instructing in personal training. The data consist of 7 h 23 min of video recordings of training sessions with Swedish-speaking participants from Finland and Sweden, which are supplemented with field notes. The theoretical–methodological framework includes interactional linguistics, ethnography of communication, and variational pragmatics. Results show that participants use all semiotic information at hand when they produce and understand phrasal instructions during personal training. This process involves the overall activity, the participants’ institutional roles as trainer and client, their body positions and movements, and trajectories of earlier interaction and embodied elements of the instructions themselves. Phrasal instructions are short; thus, they are focused and easily integrated into the ongoing physical activity. Certain differences are observed between the data from Finland and from Sweden, e.g., Finnish data have more phrasal instructions, whereas the Swedish data have more third-turn follow-ups, which may indicate cultural differences in this domain. The article concludes that phrasal utterances are not only useful as instructions in personal training but also well-suited for the activity type.
49.	Huhtamäki, Martina, et al. (författare) Tankar som styr kroppen : Instruktioner med verbet ’tänka’ vid personlig träning. 2022 Ingår i: Svenskan i Finland 19. - Vasa. - 9789526965048 - 9789526965055 ; , s. 118-132 Konferensbidrag (refereegranskat)abstract I tidigare undersökningar av personlig träning på svenska i Finland och Sverige har vi funnit att många verbala instruktioner är korta och frasformade (se Huhtamäki m.fl. 2019). Instruktioner kan dock vara längre och mer komplexa, till exempel bestå av en uppmaning och en motivering, såsom "tänk på att du kan ha bollen ännu mer så att du får ännu mer rotation" (Lindström m.fl. 2020). Här står uppmaningen i imperativ och följs av en förklarande, konsekutiv sats. En detalj som Lindström med flera (2020) upptäckte i denna kontext var att instruktioner som innehöll sekvensen 'tänk på att' var vanligare i det sverigesvenska delmaterialet än i det finlandssvenska. Detta föranledde då frågan vad tränarna gör med denna och en del andra konstruktionstyper innehållande verbet tänka: i vilka situationskontexter används de och i vilket interaktionellt syfte? Fokus för den här undersökningen ligger således på instruktioner som uttalas av den personliga tränaren och riktar sig till motionären och som innehåller verbet tänka i någon form. Vi studerar med vilka verbala, prosodiska och kroppsliga drag PT:n realiserar instruktionerna samt jämför ett finlandssvenskt och ett sverigesvenskt delmaterial.
50.	Huhtamäki, Martina, et al. (författare) Tankar som styr kroppen. Instruktioner med verbet 'tänka' vid personlig träning 2022 Ingår i: Svenskan i Finland 19. Föredrag vid den nittonde sammankomsten för beskrivningen av svenskan i Finland Vasa den 6–7 maj 2021 / Siv Björklund, Bodil Haagensen, Marianne Nordman och Anders Westerlund (red.). - Vasa : Svensk-Österbottniska Samfundet. - 2489-4338 .- 2489-4346. - 9789526965048 Konferensbidrag (refereegranskat)abstract Fokus för den här undersökningen ligger på instruktioner som uttalas av den personliga tränaren och riktar sig till motionären och som innehåller verbet 'tänka' i någon form. Exempel på sådana är 'tänk på handlederna', 'nu tänker du på magen' och 'tänk på att du ska va helt rak också'. Vi studerar med vilka verbala, prosodiska och kroppsliga drag PT:n realiserar instruktionerna samt jämför ett finlandssvenskt och ett sverigesvenskt delmaterial. Vi undersöker instruktionerna ur ett såväl kvantitativt som kvalitativt perspektiv. Liksom i vår studie av frasformade instruktioner (Huhtamäki m.fl. 2019) använder vi termen instruktion som en överkategori för diverse språkliga handlingar som inbegriper uppmaningar, direktiv och kombinationer av dessa med motiverande handlingar.

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