| 1. |
- Hallström, Hadar, et al.
(author)
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Probiotic supplements and debridement of peri-implant mucositis : a randomized controlled trial
- 2015
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In: Acta Odontologica Scandinavica. - : Taylor & Francis. - 0001-6357 .- 1502-3850. ; 74:1, s. 60-66
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Journal article (peer-reviewed)abstract
- Objective. The aim of this double-blind randomized placebo-controlled trial was to evaluate the effects of probiotic supplements in adjunct to conventional management of peri-implant mucositis.Materials and methods.Forty-nine adult patients with peri-implant mucositis were consecutively recruited after informed consent. After initial mechanical debridement and oral hygiene instructions, the patients received a topical oil application (active or placebo) followed by twice-daily intake of lozenges (active or placebo) for 3 months. The active products contained a mix of two strains of Lactobacillus reuteri. Patients were clinically monitored and sampled at baseline and after 1, 2, 4, 12 and 26 weeks. The clinical end-points were pocket-probing depth (PPD), plaque index (PI) and bleeding on probing (BOP). In addition, the subgingival microbiota was processed with checkerboard DNA-DNA hybridization and samples of gingival crevicular fluid (GCF) were analyzed for selected cytokines with the aid of multiplex immunoassays.Results.After 4 and 12 weeks, all clinical parameters were improved in both the test and the placebo group. PPD and BOP were significantly reduced compared with baseline (p < 0.05), but no significant differences were displayed between the groups. The clinical improvements persisted 3 months after the intervention. No major alterations of the subgingival microflora were disclosed and the levels of inflammatory mediators in GCF did not differ between the groups.Conclusions.Mechanical debridement and oral hygiene reinforcement resulted in clinical improvement of peri-implant mucositis and a reduction in cytokine levels. Probiotic supplements did not provide added benefit to placebo.
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| 2. |
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| 6. |
- Knutsson, Sofie, et al.
(author)
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Noncovalent Inhibitors of Mosquito Acetylcholinesterase 1 with Resistance-Breaking Potency
- 2018
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 61:23, s. 10545-10557
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Journal article (peer-reviewed)abstract
- Resistance development in insects significantly threatens the important benefits obtained by insecticide usage in vector control of disease-transmitting insects. Discovery of new chemical entities with insecticidal activity is highly desired in order to develop new insecticide candidates. Here, we present the design, synthesis, and biological evaluation of phenoxyacetamide-based inhibitors of the essential enzyme acetylcholinesterase 1 (AChE1). AChE1 is a validated insecticide target to control mosquito vectors of, e.g., malaria, dengue, and Zika virus infections. The inhibitors combine a mosquito versus human AChE selectivity with a high potency also for the resistance-conferring mutation G122S; two properties that have proven challenging to combine in a single compound. Structure activity relationship analyses and molecular dynamics simulations of inhibitor protein complexes have provided insights that elucidate the molecular basis for these properties. We also show that the inhibitors demonstrate in vivo insecticidal activity on disease-transmitting mosquitoes. Our findings support the concept of noncovalent, selective, and resistance-breaking inhibitors of AChE1 as a promising approach for future insecticide development.
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| 7. |
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| 8. |
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| 9. |
- Taal, H. Rob, et al.
(author)
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Common variants at 12q15 and 12q24 are associated with infant head circumference
- 2012
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 532-538
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Journal article (peer-reviewed)abstract
- To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
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| 10. |
- Willems, S. M., et al.
(author)
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Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness
- 2017
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Journal article (peer-reviewed)abstract
- Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P<5 × 10-8) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres (ACTG1), neuronal maintenance and signal transduction (PEX14, TGFA, SYT1), or monogenic syndromes with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality. © The Author(s) 2017.
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| 11. |
- Agnér, Ulf, et al.
(author)
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Bredäng : Miljonprogrammets föregångare
- 2018
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Reports (other academic/artistic)abstract
- Denna publikation är ett resultat av läsåret 2017-2018 i kursen Restaureringskonst vid Kungl. Konsthögskolan, arkitekturavdelningen. Årets tema var bostadsarkitektur. Förvalta, förädla, förvanska? Under läsåret undersöktes bostadsarkitekturen som kulturarv, hur bostadshus och bostadsområden förvaltas, förädlas alternativt förvanskas genom restaureringsåtgärder, förtätningar och omvandlingar. II läsårets projektstudie ingick fem bostadsområden i södra Stockholm, utvalda för att representera varsin epok i 1900-talets bostadsutveckling. En projektgrupp för varje bostadsområde gjorde studier i olika skalor, från den utvalda lägenhetens detaljer, trapphuset och bostadshuset, gården och gatan till stadsdelsnivån.
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| 12. |
- Andersson, Anna, et al.
(author)
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Microarray-based classification of a consecutive series of 121 childhood acute leukemias: prediction of leukemic and genetic subtype as well as of minimal residual disease status.
- 2007
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In: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 21:6, s. 1198-1203
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Journal article (peer-reviewed)abstract
- Gene expression analyses were performed on 121 consecutive childhood leukemias (87 B-lineage acute lymphoblastic leukemias (ALLs), 11 T-cell ALLs and 23 acute myeloid leukemias (AMLs)), investigated during an 8-year period at a single center. The supervised learning algorithm k-nearest neighbor was utilized to build gene expression predictors that could classify the ALLs/AMLs according to clinically important subtypes with high accuracy. Validation experiments in an independent data set verified the high prediction accuracies of our classifiers. B-lineage ALLs with uncharacteristic cytogenetic aberrations or with a normal karyotype displayed heterogeneous gene expression profiles, resulting in low prediction accuracies. Minimal residual disease status (MRD) in T-cell ALLs with a high (40.1%) MRD at day 29 could be classified with 100% accuracy already at the time of diagnosis. In pediatric leukemias with uncharacteristic cytogenetic aberrations or with a normal karyotype, unsupervised analysis identified two novel subgroups: one consisting mainly of cases remaining in complete remission (CR) and one containing a few patients in CR and all but one of the patients who relapsed. This study of a consecutive series of childhood leukemias confirms and extends further previous reports demonstrating that global gene expression profiling provides a valuable tool for genetic and clinical classification of childhood leukemias.
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| 13. |
- Andersson, C. David, et al.
(author)
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Benefits of statistical molecular design, covariance analysis, and reference models in QSAR : a case study on acetylcholinesterase
- 2015
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In: Journal of Computer-Aided Molecular Design. - : Springer Science and Business Media LLC. - 0920-654X .- 1573-4951. ; 29:3, s. 199-215
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Journal article (peer-reviewed)abstract
- Scientific disciplines such as medicinal- and environmental chemistry, pharmacology, and toxicology deal with the questions related to the effects small organic compounds exhort on biological targets and the compounds' physicochemical properties responsible for these effects. A common strategy in this endeavor is to establish structure-activity relationships (SARs). The aim of this work was to illustrate benefits of performing a statistical molecular design (SMD) and proper statistical analysis of the molecules' properties before SAR and quantitative structure-activity relationship (QSAR) analysis. Our SMD followed by synthesis yielded a set of inhibitors of the enzyme acetylcholinesterase (AChE) that had very few inherent dependencies between the substructures in the molecules. If such dependencies exist, they cause severe errors in SAR interpretation and predictions by QSAR-models, and leave a set of molecules less suitable for future decision-making. In our study, SAR- and QSAR models could show which molecular sub-structures and physicochemical features that were advantageous for the AChE inhibition. Finally, the QSAR model was used for the prediction of the inhibition of AChE by an external prediction set of molecules. The accuracy of these predictions was asserted by statistical significance tests and by comparisons to simple but relevant reference models.
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| 14. |
- Andresen, Astri, et al.
(author)
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Barnen och välfärdspolitiken : Nordiska barndomar 1900-2000
- 2011. - 1
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Book (other academic/artistic)abstract
- Dagens diskussion om barn och barns rättigheter och villkor tar ofta sin utgångspunkt i 1989 års barnkonvention, men dessa frågor hör inte bara till vår egen tid. I Norden har barn under hela 1900-talet haft en viktig plats i det offentliga samtalet och i välfärdspolitiken, men det uppmärksammas sällan i forskningen. I den här boken beskrivs den välfärdshistoriska utvecklingen utifrån ämnet barn i ett jämförande nordiskt perspektiv. De nordiska länderna har mycket gemensamt och det har under hela 1900-talet funnits ett nära samarbete när det gäller barnpolitik och barns rättigheter.Barnen har setts, inte bara som de enskilda nationernas framtid utan som Nordens framtid.Boken diskuterar vad nordiskt samarbete inneburit för barn både i fråga om lagstiftning och barnpolitik i praktiken, och i vilken utsträckning nordisk välfärdspolitik har utvecklats som ett resultat av samarbete, tävlan och politik komparation. Vad är nordiskt, vad är nationellt och vad är internationellt i nordiska välfärdsmodeller?
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| 15. |
- Berndt, Sonja I., et al.
(author)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
-
Journal article (peer-reviewed)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 16. |
- Björck, Cecilia, 1970, et al.
(author)
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Potentials and Challenges in Redesigning Traditional Text Seminars in Doctoral Education in Sweden
- 2023
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In: Nordisk tidsskrift for utdanning og praksis. - 2535-7697. ; 17:1, s. 72-86
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Journal article (peer-reviewed)abstract
- The text seminar has a long and strong tradition in academia, not least in postgraduate education. In these seminars, doctoral students are socialised into the research community to be able to act as researchers in an academic setting. However, research suggests that the traditional and strictly regulated form of doctoral seminars may hinder doctoral students’ learning. In response to this problem, this article presents and discusses an analysis of an attempt to redesign doctoral education seminars in Sweden by a design theoretic approach to learning. The result shows that while certain seminar forms functioned as somewhat limiting for learning, other forms and multimodal resources were able to open for alternative meaning-making and ways of staging the identity of a researcher.
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| 17. |
- Björklund, Patrik, et al.
(author)
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Västerås slott : Slott och borgar
- 2000
-
Reports (pop. science, debate, etc.)abstract
- En majoritet av dagens byggnadsuppgifter gäller att hantera det redan byggda. När vi står inför situationen att restaurera en befintlig byggnad är det viktigt att förstå olika tidsperioders stilideal liksom byggnadsteknik och material. Först då kan vi göra en väl avvägd analys, som tar tillvara och utvecklar de kvaliteter som byggnaderna själva besitter. Därför är utbildningen upplagd som ett växelspel mellan föreläsningar, seminarier, exkursioner och en för året vald studieuppgift.Slott och borgar har varit läsårets tema. Vi har valt att arbeta med Västerås och Örebro slott - två ganska bortglömda Vasaslott som är väl värda att lyfta fram. Särskilt har vi studerat de senaste 300 årens förändringar, som inte tidigare ägnats lika stora forskarmöda som medelitden och Vasatiden. I dessa två exempel finns en provkarta på estetiska, praktiska och tekniska ingrepp från Carl Hårlemans tid och fram till idag.Studierna har således omfattat både gestaltning, funktion och byggnadsteknik. Avsikten är att visa på kvaliteter i de omvandlingar och restaureringar som skett, men också att peka på problem och analysera olika möjligheter inför framtiden. Arbetet har skett i samarbete med Statens fastighetsverk och är tänkt att utgöra ett underlag till vårdprogram och framtida restaureringsinsatser.
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| 18. |
- Broadaway, K Alaine, et al.
(author)
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Loci for insulin processing and secretion provide insight into type 2 diabetes risk.
- 2023
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In: American Journal of Human Genetics. - : Elsevier. - 0002-9297 .- 1537-6605. ; 110:2, s. 284-299
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Journal article (peer-reviewed)abstract
- Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10-8), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait. Half of the alleles associated with higher proinsulin showed higher rather than lower effects on glucose levels, corresponding to different mechanisms. Proinsulin loci included genes that affect prohormone convertases, beta-cell dysfunction, vesicle trafficking, beta-cell transcriptional regulation, and lysosomes/autophagy processes. We colocalized 11 proinsulin signals with islet expression quantitative trait locus (eQTL) data, suggesting candidate genes, including ARSG, WIPI1, SLC7A14, and SIX3. The NKX6-3/ANK1 proinsulin signal colocalized with a T2D signal and an adipose ANK1 eQTL signal but not the islet NKX6-3 eQTL. Signals were enriched for islet enhancers, and we showed a plausible islet regulatory mechanism for the lead signal in the MADD locus. These results show how detailed genetic studies of an intermediate phenotype can elucidate mechanisms that may predispose one to disease.
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| 19. |
- Chu, Audrey Y, et al.
(author)
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Multiethnic genome-wide meta-analysis of ectopic fat depots identifies loci associated with adipocyte development and differentiation
- 2017
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:1, s. 125-130
-
Journal article (peer-reviewed)abstract
- Variation in body fat distribution contributes to the metabolic sequelae of obesity. The genetic determinants of body fat distribution are poorly understood. The goal of this study was to gain new insights into the underlying genetics of body fat distribution by conducting sample-size-weighted fixed-effects genome-wide association meta-analyses in up to 9,594 women and 8,738 men of European, African, Hispanic and Chinese ancestry, with and without sex stratification, for six traits associated with ectopic fat (hereinafter referred to as ectopic-fat traits). In total, we identified seven new loci associated with ectopic-fat traits (ATXN1, UBE2E2, EBF1, RREB1, GSDMB, GRAMD3 and ENSA; P < 5 × 10(-8); false discovery rate < 1%). Functional analysis of these genes showed that loss of function of either Atxn1 or Ube2e2 in primary mouse adipose progenitor cells impaired adipocyte differentiation, suggesting physiological roles for ATXN1 and UBE2E2 in adipogenesis. Future studies are necessary to further explore the mechanisms by which these genes affect adipocyte biology and how their perturbations contribute to systemic metabolic disease.
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| 20. |
- Corbin, Laura J., et al.
(author)
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Formalising recall by genotype as an efficient approach to detailed phenotyping and causal inference
- 2018
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
-
Journal article (peer-reviewed)abstract
- Detailed phenotyping is required to deepen our understanding of the biological mechanisms behind genetic associations. In addition, the impact of potentially modifiable risk factors on disease requires analytical frameworks that allow causal inference. Here, we discuss the characteristics of Recall-by-Genotype (RbG) as a study design aimed at addressing both these needs. We describe two broad scenarios for the application of RbG: studies using single variants and those using multiple variants. We consider the efficacy and practicality of the RbG approach, provide a catalogue of UK-based resources for such studies and present an online RbG study planner.
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| 21. |
- Craddock, Nick, et al.
(author)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
-
Journal article (peer-reviewed)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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| 22. |
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| 23. |
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| 24. |
- Do, Ron, et al.
(author)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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Journal article (peer-reviewed)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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| 25. |
- Drong, Alexander W, et al.
(author)
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The presence of methylation quantitative trait loci indicates a direct genetic influence on the level of DNA methylation in adipose tissue.
- 2013
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:2
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Journal article (peer-reviewed)abstract
- Genetic variants that associate with DNA methylation at CpG sites (methylation quantitative trait loci, meQTLs) offer a potential biological mechanism of action for disease associated SNPs. We investigated whether meQTLs exist in abdominal subcutaneous adipose tissue (SAT) and if CpG methylation associates with metabolic syndrome (MetSyn) phenotypes. We profiled 27,718 genomic regions in abdominal SAT samples of 38 unrelated individuals using differential methylation hybridization (DMH) together with genotypes at 5,227,243 SNPs and expression of 17,209 mRNA transcripts. Validation and replication of significant meQTLs was pursued in an independent cohort of 181 female twins. We find that, at 5% false discovery rate, methylation levels of 149 DMH regions associate with at least one SNP in a ±500 kilobase cis-region in our primary study. We sought to validate 19 of these in the replication study and find that five of these significantly associate with the corresponding meQTL SNPs from the primary study. We find that none of the 149 meQTL top SNPs is a significant expression quantitative trait locus in our expression data, but we observed association between expression levels of two mRNA transcripts and cis-methylation status. Our results indicate that DNA CpG methylation in abdominal SAT is partly under genetic control. This study provides a starting point for future investigations of DNA methylation in adipose tissue.
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