Publications by authors named "Anna Andersson"

76 Publications

Strengthening the policy framework to resolve lax implementation of the Baltic Sea Action Plan for agriculture.

Ambio 2021 Jun 18. Epub 2021 Jun 18.

Department of Agroecology, Aarhus University, Blichers Alle 20, Foulum, 8830, Tjele, Denmark.

In this perspective article, we provide recommendations for strengthening the policy framework for protecting the Baltic Sea from agricultural nutrient pollution. The most striking weakness is the lax implementation of prescribed abatement measures, particularly concerning manure management, in most countries. Institutions of the EU should also be leveraged for achieving Baltic Sea Action Plan (BSAP) goals. In contrast to the Helsinki Convention, the European Union has economic, political and legal mandates to further implementation and compliance. Equally important is the need for strengthening of local institutions, particularly Water Boards and independent agricultural advisory services in the eastern Baltic Sea Region countries. There is also an urgent need for implementation of voluntary land-use measures where EU funding available to farmers is more broadly and effectively used by providing it on the basis of estimated abatement performance, which can be realized through modelling. The enormous potential for funding performance-based schemes, manure management infrastructure and advisory services through the EU's Common Agricultural Policy are currently underutilized.
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http://dx.doi.org/10.1007/s13280-021-01573-3DOI Listing
June 2021

How unnecessarily high abatement costs and unresolved distributional issues undermine nutrient reductions to the Baltic Sea.

Ambio 2021 Jun 9. Epub 2021 Jun 9.

Finnish Environment Institute, Latokartanonkaari 11, 00790, Helsinki, Finland.

This paper systematically reviews the literature on how to reduce nutrient emissions to the Baltic Sea cost-effectively and considerations for allocating these costs fairly among countries. The literature shows conclusively that the reduction targets of the Baltic Sea Action Plan (BSAP) could be achieved at considerably lower cost, if countries would cooperate to implement the least costly abatement plan. Focusing on phosphorus abatement could be prudent as the often recommended measures-wastewater treatment and wetlands-abate nitrogen too. An implication of our review is that the potential for restoring the Baltic Sea to good health is undermined by an abatement strategy that is more costly than necessary and likely to be perceived as unfair by several countries. Neither the BSAP nor the cost-effective solution meet the surveyed criteria for fairness, implying a need for side-payments.
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http://dx.doi.org/10.1007/s13280-021-01580-4DOI Listing
June 2021

Definitions and Operationalization of Mental Health Problems, Wellbeing and Participation Constructs in Children with NDD: Distinctions and Clarifications.

Int J Environ Res Public Health 2021 02 9;18(4). Epub 2021 Feb 9.

School of Health, Care and Social Welfare, Mälardalen University, 72123 Vasteras, Sweden.

Children with impairments are known to experience more restricted participation than other children. It also appears that low levels of participation are related to a higher prevalence of mental health problems in children with neurodevelopmental disorders (NDD). The purpose of this conceptual paper is to describe and define the constructs mental health problems, mental health, and participation to ensure that future research investigating participation as a means to mental health in children and adolescents with NDD is founded on conceptual clarity. We first discuss the difference between two aspects of , namely mental disorder and mental illness. This discussion serves to highlight three areas of conceptual difficulty and their consequences for understanding the mental health of children with NDD that we then consider in the article: (1) how to define mental health problems, (2) how to define and assess mental health problems and mental health, i.e., wellbeing as separate constructs, and (3) how to describe the relationship between participation and wellbeing. We then discuss the implications of our propositions for measurement and the use of participation interventions as a means to enhance mental health (defined as wellbeing). Conclusions: Mental disorders include both diagnoses related to impairments in the developmental period, i.e., NDD and diagnoses related to mental illness. These two types of mental disorders must be separated. Children with NDD, just like other people, may exhibit aspects of both and wellbeing simultaneously. Measures of wellbeing defined as a continuum from flourishing to languishing for children with NDD need to be designed and evaluated. Wellbeing can lead to further participation and act to protect from mental health problems.
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http://dx.doi.org/10.3390/ijerph18041656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916140PMC
February 2021

DNA Methylation Levels in Mononuclear Leukocytes from the Mother and Her Child Are Associated with IgE Sensitization to Allergens in Early Life.

Int J Mol Sci 2021 Jan 14;22(2). Epub 2021 Jan 14.

Department of Clinical Science and Education, Karolinska Institutet, and Sachs' Children and Youth Hospital, Södersjukhuset, SE-118 83 Stockholm, Sweden.

DNA methylation changes may predispose becoming IgE-sensitized to allergens. We analyzed whether DNA methylation in peripheral blood mononuclear cells (PBMC) is associated with IgE sensitization at 5 years of age (5Y). DNA methylation was measured in 288 PBMC samples from 74 mother/child pairs from the birth cohort ALADDIN (Assessment of Lifestyle and Allergic Disease During INfancy) using the HumanMethylation450BeadChip (Illumina). PBMCs were obtained from the mothers during pregnancy and from their children in cord blood, at 2 years and 5Y. DNA methylation levels at each time point were compared between children with and without IgE sensitization to allergens at 5Y. For replication, CpG sites associated with IgE sensitization in ALADDIN were evaluated in whole blood DNA of 256 children, 4 years old, from the BAMSE (Swedish abbreviation for Children, Allergy, Milieu, Stockholm, Epidemiology) cohort. We found 34 differentially methylated regions (DMRs) associated with IgE sensitization to airborne allergens and 38 DMRs associated with sensitization to food allergens in children at 5Y (Sidak ≤ 0.05). Genes associated with airborne sensitization were enriched in the pathway of endocytosis, while genes associated with food sensitization were enriched in focal adhesion, the bacterial invasion of epithelial cells, and leukocyte migration. Furthermore, 25 DMRs in maternal PBMCs were associated with IgE sensitization to airborne allergens in their children at 5Y, which were functionally annotated to the mTOR (mammalian Target of Rapamycin) signaling pathway. This study supports that DNA methylation is associated with IgE sensitization early in life and revealed new candidate genes for atopy. Moreover, our study provides evidence that maternal DNA methylation levels are associated with IgE sensitization in the child supporting early in utero effects on atopy predisposition.
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http://dx.doi.org/10.3390/ijms22020801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830007PMC
January 2021

Unraveling the chemodiversity of halogenated disinfection by-products formed during drinking water treatment using target and non-target screening tools.

J Hazard Mater 2021 01 15;401:123681. Epub 2020 Aug 15.

Department of Aquatic Sciences and Assessment, Swedish University of Agricultural Sciences (SLU), Box 7050, SE-750 07, Uppsala, Sweden.

To date, there is no analytical approach available that allows the full identification and characterization of highly complex disinfection by-product (DBP) mixtures. This study aimed at investigating the chemodiversity of drinking water halogenated DBPs using diverse analytical tools: measurement of adsorbable organic halogen (AOX) and mass spectrometry (MS)-based target and non-target analytical workflows. Water was sampled before and after chemical disinfection (chlorine or chloramine) at four drinking water treatment plants in Sweden. The target analysis had the highest sensitivity, although it could only partially explain the AOX formed in the disinfected waters. Non-target Fourier transform ion cyclotron resonance (FT-ICR) MS analysis indicated that only up to 19 Cl and/or Br-CHO formulae were common to all disinfected waters. Unexpectedly, a high diversity of halogenated DBPs (presumed halogenated polyphenolic and highly unsaturated compounds) was found in chloraminated surface water, comparable to that found in chlorinated surface water. Overall, up to 86 DBPs (including isobaric species) were tentatively identified using liquid chromatography (LC)-Orbitrap MS. Although further work is needed to confirm their identity and assess their relevance in terms of toxicity, they can be used to design suspect lists to improve the characterization of disinfected water halogenated mixtures.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123681DOI Listing
January 2021

Epigenetic alterations in skin homing CD4CLA T cells of atopic dermatitis patients.

Sci Rep 2020 10 22;10(1):18020. Epub 2020 Oct 22.

Department of Clinical Science and Education, Karolinska Institutet, and Sachs' Children and Youth Hospital, Södersjukhuset, 118 83, Stockholm, Sweden.

T cells expressing the cutaneous lymphocyte antigen (CLA) mediate pathogenic inflammation in atopic dermatitis (AD). The molecular alterations contributing to their dysregulation remain unclear. With the aim to elucidate putative altered pathways in AD we profiled DNA methylation levels and miRNA expression in sorted T cell populations (CD4, CD4CD45RA naïve, CD4CLA, and CD8) from adult AD patients and healthy controls (HC). Skin homing CD4CLA T cells from AD patients showed significant differences in DNA methylation in 40 genes compared to HC (p < 0.05). Reduced DNA methylation levels in the upstream region of the interleukin-13 gene (IL13) in CD4CLA T cells from AD patients correlated with increased IL13 mRNA expression in these cells. Sixteen miRNAs showed differential expression in CD4CLA T cells from AD patients targeting genes in 202 biological processes (p < 0.05). An integrated network analysis of miRNAs and CpG sites identified two communities of strongly interconnected regulatory elements with strong antagonistic behaviours that recapitulated the differences between AD patients and HC. Functional analysis of the genes linked to these communities revealed their association with key cytokine signaling pathways, MAP kinase signaling and protein ubiquitination. Our findings support that epigenetic mechanisms play a role in the pathogenesis of AD by affecting inflammatory signaling molecules in skin homing CD4CLA T cells and uncover putative molecules participating in AD pathways.
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http://dx.doi.org/10.1038/s41598-020-74798-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582180PMC
October 2020

Agreement between participation ratings of children with intellectual disabilities and their primary caregivers.

Res Dev Disabil 2020 Sep 20;104:103715. Epub 2020 Jun 20.

CHILD Research Group, Swedish Institute for Disability Research, School of Health and Welfare, Jönkoping University Sweden, Sweden.

Background: Participation of children with ID it is argued must be understood in relation to the fit with the environment. Since caregivers are a vital factor within the close environment of a child with intellectual disability, their perceptions are unequivocally important.

Aims: The main aim of this study is to describe the self-reported participation of children with ID and the perceptions of their primary caregivers. Both frequency of attendance and perceived importance of activity was measured with self-reported and proxy-reports.

Methods & Procedures: A custom developed Picture my Participation (PmP) survey was utilised in an interview format with children with intellectual disability whilst their primary caregivers completed the survey independently.

Results: Overall, the perceptions of children with intellectual disabilities and of primary caregivers showed similarities regarding attendance and activities considered important. On group level, both children and primary caregivers perceived the child to have a high level of attendance ofFormal learning in school, Family mealtime, Interacting with family and Celebrations. An overall poor agreement in perceived frequency of attendance was found. However, in child-primary cargiver-dyads poor agreement in perceived frequency of attendance was found.

Conclusions: While primary caregivers and children's ratings of attendance and selection of the most important activities appeared somewhat similar, there was a noted difference, in that primary caregivers' were uniform in their selection, whilst there was a diversity in the selection of activities amongst children.
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http://dx.doi.org/10.1016/j.ridd.2020.103715DOI Listing
September 2020

Author Correction: Extracellular nanovesicles released from the commensal yeast Malassezia sympodialis are enriched in allergens and interact with cells in human skin.

Sci Rep 2019 Oct 15;9(1):15014. Epub 2019 Oct 15.

Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, and Unit Sachs' Children and Youth Hospital, Södersjukhuset, SE-118 83, Stockholm, Sweden.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
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http://dx.doi.org/10.1038/s41598-019-43724-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791871PMC
October 2019

Adaptation of the Canine Orthopaedic Index to evaluate chronic elbow osteoarthritis in Swedish dogs.

Acta Vet Scand 2019 Jun 20;61(1):29. Epub 2019 Jun 20.

Department of Clinical Sciences, Swedish University of Agricultural Sciences, Box 7054, 75007, Uppsala, Sweden.

Background: Owner questionnaires may be used to assess osteoarthritis (OA) in dogs. The validated American College of Veterinary Surgeons' (ACVS) Canine Orthopaedic Index Questionnaire quantifies quality of life in dogs with orthopaedic disease. This index was modified and translated into Swedish and evaluated for validity, reliability and sensitivity. One group with confirmed moderate elbow dysplasia (n = 117) and one healthy control group (n = 146) without radiographic elbow disease and without lameness were included. Telephone interviews with the dog owners were conducted throughout the study using owner-completed questionnaires.

Results: A 16-item questionnaire developed from an initial data set including 22 items, were able to differentiate between the affected group and the control group with good readability. Validity was measured through factor analysis which yielded a three-factor model accounting for 66.3% of the variance. Cronbach's α was 0.89 for the total instrument, > 0.7 for stiffness, lameness and function, but < 0.7 for quality of life. Based on the process the modified questionnaire can be used in Swedish, as the ACVS COI, to make intra-patient comparisons and evaluation of disease progression.

Conclusions: A sound owner-completed questionnaire translated into Swedish and modified, able to differ healthy dogs from dogs suffering from chronic osteoarthritis is presented. Performed statistical analysis show the items of the instrument to be reasonable and have high construct validity. The questionnaire may be used in the clinical setting and for research.
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http://dx.doi.org/10.1186/s13028-019-0465-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585128PMC
June 2019

Innovative drinking water treatment techniques reduce the disinfection-induced oxidative stress and genotoxic activity.

Water Res 2019 May 28;155:182-192. Epub 2019 Feb 28.

Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Box 7028, SE-750 07, Uppsala, Sweden.

Disinfection of drinking water using chlorine can lead to the formation of genotoxic by-products when chlorine reacts with natural organic matter (NOM). A vast number of such disinfection by-products (DBPs) have been identified, making it almost impossible to routinely monitor all DBPs with chemical analysis. In this study, a bioanalytical approach was used, measuring oxidative stress (Nrf2 activity), genotoxicity (micronucleus test), and aryl hydrocarbon receptor (AhR) activation to evaluate an innovative water treatment process, including suspended ion exchange, ozonation, in-line coagulation, ceramic microfiltration, and granular activated carbon. Chlorination was performed in laboratory scale after each step in the treatment process in order to investigate the effect of each treatment process to the formation of DBPs. Suspended ion exchange had a high capacity to remove dissolved organic carbon (DOC) and to decrease UV absorbance and Nrf2 activity in non-chlorinated water. High-dose chlorination (10 mg Cl L) of raw water caused a drastic induction of Nrf2 activity, which was decreased by 70% in water chlorinated after suspended ion exchange. Further reduction of Nrf2 activity following chlorination was achieved by ozonation and the concomitant treatment steps. The ozonation treatment resulted in decreased Nrf2 activity in spite of unchanged DOC levels. However, a strong correlation was found between UV absorbing compounds and Nrf2 activity, demonstrating that Nrf2 inducing DBPs were formed from pre-cursors of a specific NOM fraction, constituted of mainly aromatic compounds. Moreover, high-dose chlorination of raw water induced genotoxicity. In similarity to the DOC levels, UV absorbance and Nrf2 activity, the disinfection-induced genotoxicity was also reduced by each treatment step of the innovative water treatment technique. AhR activity was observed in the water produced by the conventional process and in the raw water, but the activity was clearly decreased by the ozonation step in the innovative water treatment process.
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http://dx.doi.org/10.1016/j.watres.2019.02.052DOI Listing
May 2019

Extracellular nanovesicles released from the commensal yeast Malassezia sympodialis are enriched in allergens and interact with cells in human skin.

Sci Rep 2018 06 15;8(1):9182. Epub 2018 Jun 15.

Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, and Unit Sachs' Children and Youth Hospital, Södersjukhuset, SE-118 83, Stockholm, Sweden.

Malassezia sympodialis is a dominant commensal fungi in the human skin mycobiome but is also associated with common skin disorders including atopic eczema (AE). M. sympodialis releases extracellular vesicles, designated MalaEx, which are carriers of small RNAs and allergens, and they can induce inflammatory cytokine responses. Here we explored how MalaEx are involved in host-microbe interactions by comparing protein content of MalaEx with that of the parental yeast cells, and by investigating interactions of MalaEx with cells in the skin. Cryo-electron tomography revealed a heterogeneous population of MalaEx. iTRAQ based quantitative proteomics identified in total 2439 proteins in all replicates of which 110 were enriched in MalaEx compared to the yeast cells. Among the MalaEx enriched proteins were two of the M. sympodialis allergens, Mala s 1 and s 7. Functional experiments indicated an active binding and internalization of MalaEx into human keratinocytes and monocytes, and MalaEx were found in close proximity of the nuclei using super-resolution fluorescence 3D-SIM imaging. Our results provides new insights into host-microbe interactions, supporting that MalaEx may have a role in the sensitization and maintenance of inflammation in AE by containing enriched amounts of allergens and with their ability to interact with skin cells.
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http://dx.doi.org/10.1038/s41598-018-27451-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6004016PMC
June 2018

Evaluating gas chromatography with a halogen-specific detector for the determination of disinfection by-products in drinking water.

Environ Sci Pollut Res Int 2019 Mar 28;26(8):7305-7314. Epub 2018 Feb 28.

Department of Thematic Studies-Environmental Change, Linköping University, SE-581 83, Linköping, Sweden.

The occurrence of disinfection by-products (DBPs) in drinking water has become an issue of concern during the past decades. The DBPs pose health risks and are suspected to cause various cancer forms, be genotoxic, and have negative developmental effects. The vast chemical diversity of DBPs makes comprehensive monitoring challenging. Only few of the DBPs are regulated and included in analytical protocols. In this study, a method for simultaneous measurement of 20 DBPs from five different structural classes (both regulated and non-regulated) was investigated and further developed for 11 DBPs using solid-phase extraction and gas chromatography coupled with a halogen-specific detector (XSD). The XSD was highly selective towards halogenated DBPs, providing chromatograms with little noise. The method allowed detection down to 0.05 μg L and showed promising results for the simultaneous determination of a range of neutral DBP classes. Compounds from two classes of emerging DBPs, more cytotoxic than the "traditional" regulated DBPs, were successfully determined using this method. However, haloacetic acids (HAAs) should be analyzed separately as some HAA methyl esters may degrade giving false positives of trihalomethanes (THMs). The method was tested on real water samples from two municipal waterworks where the target DBP concentrations were found below the regulatory limits of Sweden.
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http://dx.doi.org/10.1007/s11356-018-1419-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447507PMC
March 2019

The importance of a complete declaration of isothiazolinones in products beyond cosmetics.

Contact Dermatitis 2017 Sep;77(3):171-172

Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, 2900 Hellerup, Denmark.

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http://dx.doi.org/10.1111/cod.12755DOI Listing
September 2017

Patterns of everyday functioning in preschool children born preterm and at term.

Res Dev Disabil 2017 Aug 23;67:82-93. Epub 2017 Jun 23.

School of Health, Care and Welfare, Mälardalen University, Box 883, SE-721 23 Västerås, Sweden. Electronic address:

Background/aim: Children born preterm are at risk of neonatal complications but the long-term consequences for everyday functioning is not well known. The study aimed to identify patterns of everyday functioning in preschool children born preterm and at term in relation to perinatal data, neonatal risk factors, behaviour, and socioeconomic status. Registry data and data from parent rated questionnaires were collected for 331 children.

Method: A person-oriented approach with a cluster analysis was used.

Results: A seven cluster solution explained 65.91% of the variance. Most children (n=232) showed patterns of strong everyday functioning. A minority of the children (n=99), showed diverse patterns of weak everyday functioning. Perinatal characteristics, neonatal risk factors and socio-economics did not predict cluster group membership. Children born preterm were represented in all clusters.

Conclusion, Implications: Most preschool children are perceived by their parents with strong everyday functioning despite being born preterm. However small groups of children are, for various reasons, perceived with weak functioning, but preterm birth is not the sole contributor to patterns of weak everyday functioning. More critical for all children's everyday functioning is probably the interaction between individual factors, behavioural factors and contextual factors. To gain a broader understanding of children's everyday functioning. Child Health Services need to systematically consider aspects of body function, activity and in addition participation and environmental aspects.
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http://dx.doi.org/10.1016/j.ridd.2017.06.005DOI Listing
August 2017

Biased partitioning of the multidrug efflux pump AcrAB-TolC underlies long-lived phenotypic heterogeneity.

Science 2017 04;356(6335):311-315

Institute of Science and Technology Austria, 3400 Klosterneuburg, Austria.

The molecular mechanisms underlying phenotypic variation in isogenic bacterial populations remain poorly understood. We report that AcrAB-TolC, the main multidrug efflux pump of exhibits a strong partitioning bias for old cell poles by a segregation mechanism that is mediated by ternary AcrAB-TolC complex formation. Mother cells inheriting old poles are phenotypically distinct and display increased drug efflux activity relative to daughters. Consequently, we find systematic and long-lived growth differences between mother and daughter cells in the presence of subinhibitory drug concentrations. A simple model for biased partitioning predicts a population structure of long-lived and highly heterogeneous phenotypes. This straightforward mechanism of generating sustained growth rate differences at subinhibitory antibiotic concentrations has implications for understanding the emergence of multidrug resistance in bacteria.
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http://dx.doi.org/10.1126/science.aaf4762DOI Listing
April 2017

Proteogenomics produces comprehensive and highly accurate protein-coding gene annotation in a complete genome assembly of Malassezia sympodialis.

Nucleic Acids Res 2017 03;45(5):2629-2643

Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, 17121 Solna, Sweden.

Complete and accurate genome assembly and annotation is a crucial foundation for comparative and functional genomics. Despite this, few complete eukaryotic genomes are available, and genome annotation remains a major challenge. Here, we present a complete genome assembly of the skin commensal yeast Malassezia sympodialis and demonstrate how proteogenomics can substantially improve gene annotation. Through long-read DNA sequencing, we obtained a gap-free genome assembly for M. sympodialis (ATCC 42132), comprising eight nuclear and one mitochondrial chromosome. We also sequenced and assembled four M. sympodialis clinical isolates, and showed their value for understanding Malassezia reproduction by confirming four alternative allele combinations at the two mating-type loci. Importantly, we demonstrated how proteomics data could be readily integrated with transcriptomics data in standard annotation tools. This increased the number of annotated protein-coding genes by 14% (from 3612 to 4113), compared to using transcriptomics evidence alone. Manual curation further increased the number of protein-coding genes by 9% (to 4493). All of these genes have RNA-seq evidence and 87% were confirmed by proteomics. The M. sympodialis genome assembly and annotation presented here is at a quality yet achieved only for a few eukaryotic organisms, and constitutes an important reference for future host-microbe interaction studies.
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http://dx.doi.org/10.1093/nar/gkx006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389616PMC
March 2017

Identification of small RNAs in extracellular vesicles from the commensal yeast Malassezia sympodialis.

Sci Rep 2017 01 4;7:39742. Epub 2017 Jan 4.

Department of Clinical Science and Education, Karolinska Institutet, and Sachs' Children and Youth Hospital, Södersjukhuset, SE-118 83 Stockholm, Sweden.

Malassezia is the dominant fungus in the human skin mycobiome and is associated with common skin disorders including atopic eczema (AE)/dermatitis. Recently, it was found that Malassezia sympodialis secretes nanosized exosome-like vesicles, designated MalaEx, that carry allergens and can induce inflammatory cytokine responses. Extracellular vesicles from different cell-types including fungi have been found to deliver functional RNAs to recipient cells. In this study we assessed the presence of small RNAs in MalaEx and addressed if the levels of these RNAs differ when M. sympodialis is cultured at normal human skin pH versus the elevated pH present on the skin of patients with AE. The total number and the protein concentration of the released MalaEx harvested after 48 h culture did not differ significantly between the two pH conditions nor did the size of the vesicles. From small RNA sequence data, we identified a set of reads with well-defined start and stop positions, in a length range of 16 to 22 nucleotides consistently present in the MalaEx. The levels of small RNAs were not significantly differentially expressed between the two different pH conditions indicating that they are not influenced by the elevated pH level observed on the AE skin.
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http://dx.doi.org/10.1038/srep39742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5209728PMC
January 2017

The genomic landscape of core-binding factor acute myeloid leukemias.

Nat Genet 2016 12 31;48(12):1551-1556. Epub 2016 Oct 31.

Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

Acute myeloid leukemia (AML) comprises a heterogeneous group of leukemias frequently defined by recurrent cytogenetic abnormalities, including rearrangements involving the core-binding factor (CBF) transcriptional complex. To better understand the genomic landscape of CBF-AMLs, we analyzed both pediatric (n = 87) and adult (n = 78) samples, including cases with RUNX1-RUNX1T1 (n = 85) or CBFB-MYH11 (n = 80) rearrangements, by whole-genome or whole-exome sequencing. In addition to known mutations in the Ras pathway, we identified recurrent stabilizing mutations in CCND2, suggesting a previously unappreciated cooperating pathway in CBF-AML. Outside of signaling alterations, RUNX1-RUNX1T1 and CBFB-MYH11 AMLs demonstrated remarkably different spectra of cooperating mutations, as RUNX1-RUNX1T1 cases harbored recurrent mutations in DHX15 and ZBTB7A, as well as an enrichment of mutations in epigenetic regulators, including ASXL2 and the cohesin complex. This detailed analysis provides insights into the pathogenesis and development of CBF-AML, while highlighting dramatic differences in the landscapes of cooperating mutations for these related AML subtypes.
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http://dx.doi.org/10.1038/ng.3709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5508996PMC
December 2016

Combinatorial Study of Gradient Ag-Al Thin Films: Microstructure, Phase Formation, Mechanical and Electrical Properties.

ACS Appl Mater Interfaces 2016 Nov 31;8(44):30635-30643. Epub 2016 Oct 31.

Department of Chemistry-Ångström Laboratory, Uppsala University , PO Box 538, SE-751 21 Uppsala, Sweden.

A combinatorial approach is applied to rapidly deposit and screen Ag-Al thin films to evaluate the mechanical, tribological, and electrical properties as a function of chemical composition. Ag-Al thin films with large continuous composition gradients (6-60 atom % Al) were deposited by a custom-designed combinatorial magnetron sputtering system. X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX), scanning and transmission electron microscopy (SEM and TEM), X-ray photoelectron spectroscopy (XPS), nanoindentation, and four-point electrical resistance screening were employed to characterize the chemical composition, structure, and physical properties of the films in a time-efficient way. For low Al contents (<13 atom %), a highly (111)-textured fcc phase was formed. At higher Al contents, a (002)-textured hcp solid solution phase was formed followed by a fcc phase in the most Al-rich regions. No indication of a μ phase was observed. The Ag-Al films with fcc-Ag matrix is prone to adhesive material transfer leading to a high friction coefficient (>1) and adhesive wear, similar to the behavior of pure Ag. In contrast, the hexagonal solid solution phase (from ca. 15 atom %Al) exhibited dramatically reduced friction coefficients (about 15% of that of the fcc phase) and dramatically reduced adhesive wear when tested against the pure Ag counter surface. The increase in contact resistance of the Ag-Al films is limited to only 50% higher than a pure Ag reference sample at the low friction and low wear region (19-27 atom %). This suggests that a hcp Ag-Al alloy can have a potential use in sliding electrical contact applications and in the future will replace pure Ag in specific electromechanical applications.
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http://dx.doi.org/10.1021/acsami.6b10659DOI Listing
November 2016

Predictors for everyday functioning in preschool children born preterm and at term.

Early Hum Dev 2016 12 26;103:147-153. Epub 2016 Sep 26.

School of Health, Care and Welfare, Mälardalen University, Box 883, SE 721 23 Västerås, Sweden. Electronic address:

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http://dx.doi.org/10.1016/j.earlhumdev.2016.09.011DOI Listing
December 2016

Identification of ETV6-RUNX1-like and DUX4-rearranged subtypes in paediatric B-cell precursor acute lymphoblastic leukaemia.

Nat Commun 2016 06 6;7:11790. Epub 2016 Jun 6.

Department of Laboratory Medicine, Division of Clinical Genetics, Lund University, Lund 22184, Sweden.

Fusion genes are potent driver mutations in cancer. In this study, we delineate the fusion gene landscape in a consecutive series of 195 paediatric B-cell precursor acute lymphoblastic leukaemia (BCP ALL). Using RNA sequencing, we find in-frame fusion genes in 127 (65%) cases, including 27 novel fusions. We describe a subtype characterized by recurrent IGH-DUX4 or ERG-DUX4 fusions, representing 4% of cases, leading to overexpression of DUX4 and frequently co-occurring with intragenic ERG deletions. Furthermore, we identify a subtype characterized by an ETV6-RUNX1-like gene-expression profile and coexisting ETV6 and IKZF1 alterations. Thus, this study provides a detailed overview of fusion genes in paediatric BCP ALL and adds new pathogenetic insights, which may improve risk stratification and provide therapeutic options for this disease.
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http://dx.doi.org/10.1038/ncomms11790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4897744PMC
June 2016

Genomic profiling and directed ex vivo drug analysis of an unclassifiable myelodysplastic/myeloproliferative neoplasm progressing into acute myeloid leukemia.

Genes Chromosomes Cancer 2016 11 4;55(11):847-54. Epub 2016 Jul 4.

Faculty of Medicine, Department of Laboratory Medicine Lund, Division of Clinical Genetics, Lund University, Lund, Sweden.

Myelodysplastic/myeloproliferative neoplasms, unclassifiable (MDS/MPN-U) are rare genetically heterogeneous hematologic diseases associated with older age and a poor prognosis. If the disease progresses into acute myeloid leukemia (AML), it is often refractory to treatment. To gain insight into genetic alterations associated with disease progression, whole exome sequencing and single nucleotide polymorphism arrays were used to characterize the bone marrow and blood samples from a 39-year-old woman at MDS/MPN-U diagnosis and at AML progression, in which routine genetic diagnostics had not identified any genetic alterations. The data revealed the presence of a partial tandem duplication of the MLL gene as the only detectable copy number change and 11 non-silent somatic mutations, including DNMT3A R882H and NRAS G13D. All somatic lesions were present both at initial MDS/MPN-U diagnosis and at AML presentation at similar mutant allele frequencies. The patient has since had two extramedullary relapses and is at high risk of a future bone marrow relapse. A directed ex vivo drug sensitivity analysis showed that the patient's AML cells are sensitive to, for example, the MEK inhibitor trametinib and the proteasome inhibitor bortezomib, indicating that she may benefit from treatment with these drugs. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/gcc.22384DOI Listing
November 2016

To build a bridge between two worlds: Mothers' experiences of professional support at the maternity ward.

Health Care Women Int 2016 10 23;37(10):1067-81. Epub 2015 Sep 23.

d School of Health and Education, University of Skövde , Skövde , Sweden.

We studied the experience of professional support among first-time mothers in relation to a scale measuring professional support in maternity care. We used a qualitative study with both an inductive and deductive approach and interviewed nine mothers. Our findings, both inductive and deductive, suggest that first-time mothers expect professional support in their transition into motherhood, building a bridge between two worlds. The first meeting, acknowledging individual needs, and supporting partner participation were important for good support. Maternity care should be organized with a focus on availability and professional support for mothers and the increased participation of their partners. Our scale of measurement can be useful but needs some development.
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http://dx.doi.org/10.1080/07399332.2015.1094072DOI Listing
October 2016

Male reproductive disorders, diseases, and costs of exposure to endocrine-disrupting chemicals in the European Union.

J Clin Endocrinol Metab 2015 Apr 5;100(4):1267-77. Epub 2015 Mar 5.

Department of Environmental Health (R.H.), Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115; Department of Growth and Reproduction (N.E.S., A.J., A.M.A.), Rigshospitalet, EDMaRC and University of Copenhagen, DK-2100 Copenhagen, Denmark; National Food Institute (U.H.), Technical University of Denmark, 2800 Kgs Søborg, Denmark; Departments of Physiology and Pediatrics (J.T.), University of Turku, 20014 Turku, Finland; Brunel University (A.K.), London UB8 3PH, United Kingdom; National Institute of Environmental Health Sciences (J.J.H.), Division of Extramural Research and Training, Research Triangle Park, North Carolina 27709; New York University (NYU) School of Medicine (L.T.), New York, New York 10016; NYU Wagner School of Public Service (L.T.), New York, New York 10012; NYU Steinhardt School of Culture, Education, and Human Development (L.T.), Department of Nutrition, Food, and Public Health, New York, New York 10003; and NYU Global Institute of Public Health (L.T.), New York, New York 10003.

Introduction: Increasing evidence suggests that endocrine-disrupting chemicals (EDCs) contribute to male reproductive diseases and disorders.

Purpose: To estimate the incidence/prevalence of selected male reproductive disorders/diseases and associated economic costs that can be reasonably attributed to specific EDC exposures in the European Union (EU).

Methods: An expert panel evaluated evidence for probability of causation using the Intergovernmental Panel on Climate Change weight-of-evidence characterization. Exposure-response relationships and reference levels were evaluated, and biomarker data were organized from carefully identified studies from the peer-reviewed literature to represent European exposure and approximate burden of disease as it occurred in 2010. The cost-of-illness estimation utilized multiple peer-reviewed sources.

Results: The expert panel identified low epidemiological and strong toxicological evidence for male infertility attributable to phthalate exposure, with a 40-69% probability of causing 618,000 additional assisted reproductive technology procedures, costing €4.71 billion annually. Low epidemiological and strong toxicological evidence was also identified for cryptorchidism due to prenatal polybrominated diphenyl ether exposure, resulting in a 40-69% probability that 4615 cases result, at a cost of €130 million (sensitivity analysis, €117-130 million). A much more modest (0-19%) probability of causation in testicular cancer by polybrominated diphenyl ethers was identified due to very low epidemiological and weak toxicological evidence, with 6830 potential cases annually and costs of €848 million annually (sensitivity analysis, €313-848 million). The panel assigned 40-69% probability of lower T concentrations in 55- to 64-year-old men due to phthalate exposure, with 24 800 associated deaths annually and lost economic productivity of €7.96 billion.

Conclusions: EDCs may contribute substantially to male reproductive disorders and diseases, with nearly €15 billion annual associated costs in the EU. These estimates represent only a few EDCs for which there were sufficient epidemiological studies and those with the highest probability of causation. These public health costs should be considered as the EU contemplates regulatory action on EDCs.
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http://dx.doi.org/10.1210/jc.2014-4325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4399287PMC
April 2015

The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias.

Nat Genet 2015 Apr 2;47(4):330-7. Epub 2015 Mar 2.

Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

Infant acute lymphoblastic leukemia (ALL) with MLL rearrangements (MLL-R) represents a distinct leukemia with a poor prognosis. To define its mutational landscape, we performed whole-genome, exome, RNA and targeted DNA sequencing on 65 infants (47 MLL-R and 18 non-MLL-R cases) and 20 older children (MLL-R cases) with leukemia. Our data show that infant MLL-R ALL has one of the lowest frequencies of somatic mutations of any sequenced cancer, with the predominant leukemic clone carrying a mean of 1.3 non-silent mutations. Despite this paucity of mutations, we detected activating mutations in kinase-PI3K-RAS signaling pathway components in 47% of cases. Surprisingly, these mutations were often subclonal and were frequently lost at relapse. In contrast to infant cases, MLL-R leukemia in older children had more somatic mutations (mean of 6.5 mutations/case versus 1.3 mutations/case, P = 7.15 × 10(-5)) and had frequent mutations (45%) in epigenetic regulators, a category of genes that, with the exception of MLL, was rarely mutated in infant MLL-R ALL.
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http://dx.doi.org/10.1038/ng.3230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4553269PMC
April 2015

Establishment of stably transfected cells constitutively expressing the full-length and truncated antigenic proteins of two genetically distinct mink astroviruses.

PLoS One 2013 23;8(12):e82978. Epub 2013 Dec 23.

Joint R&D Division of Virology, Department of Virology, Immunobiology and Parasitology, The National Veterinary Institute (SVA), Uppsala, Sweden.

Astroviruses are becoming a growing concern in veterinary and public health. To date there are no registered vaccines against astrovirus-induced disease, mostly due to the difficulty to cultivate astroviruses to high titer for vaccine development using conventional techniques. As means to circumvent this drawback, we have developed stably transfected mink fetal cells and BHK21 cells constitutively expressing the full-length and truncated capsid proteins of two distinct genotypes of mink astrovirus. Protein expression in these stably transfected cells was demonstrated by strong signals as evaluated by in-situ PLA and IFA, and confirmed by Western blotting. The recombinant full-length and truncated proteins induced a high level of antibodies in mink, evaluated by ELISA, demonstrating their immunogenicity. In a challenge experiment in mink, a reduction in presentation clinical signs and virus shedding was observed in mink kits born from immunized females. The gene integration and protein expression were sustained through cell passage, showing that the used approach is robust and reliable for expression of functional capsid proteins for vaccine and diagnostic applications.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0082978PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3871642PMC
October 2014

Integrated genetic and epigenetic analysis of childhood acute lymphoblastic leukemia.

J Clin Invest 2013 Jul 10;123(7):3099-111. Epub 2013 Jun 10.

Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.

Acute lymphoblastic leukemia (ALL) is the commonest childhood malignancy and is characterized by recurring structural genetic alterations. Previous studies of DNA methylation suggest epigenetic alterations may also be important, but an integrated genome-wide analysis of genetic and epigenetic alterations in ALL has not been performed. We analyzed 137 B-lineage and 30 T-lineage childhood ALL cases using microarray analysis of DNA copy number alterations and gene expression, and genome-wide cytosine methylation profiling using the HpaII tiny fragment enrichment by ligation-mediated PCR (HELP) assay. We found that the different genetic subtypes of ALL are characterized by distinct DNA methylation signatures that exhibit significant correlation with gene expression profiles. We also identified an epigenetic signature common to all cases, with correlation to gene expression in 65% of these genes, suggesting that a core set of epigenetically deregulated genes is central to the initiation or maintenance of lymphoid transformation. Finally, we identified aberrant methylation in multiple genes also targeted by recurring DNA copy number alterations in ALL, suggesting that these genes are inactivated far more frequently than suggested by structural genomic analyses alone. Together, these results demonstrate subtype- and disease-specific alterations in cytosine methylation in ALL that influence transcriptional activity, and are likely to exert a key role in leukemogenesis.
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http://dx.doi.org/10.1172/JCI66203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696550PMC
July 2013

Genomic insights into the atopic eczema-associated skin commensal yeast Malassezia sympodialis.

mBio 2013 Jan 22;4(1):e00572-12. Epub 2013 Jan 22.

Science for Life Laboratory, Translational Immunology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.

Unlabelled: Malassezia commensal yeasts are associated with a number of skin disorders, such as atopic eczema/dermatitis and dandruff, and they also can cause systemic infections. Here we describe the 7.67-Mbp genome of Malassezia sympodialis, a species associated with atopic eczema, and contrast its genome repertoire with that of Malassezia globosa, associated with dandruff, as well as those of other closely related fungi. Ninety percent of the predicted M. sympodialis protein coding genes were experimentally verified by mass spectrometry at the protein level. We identified a relatively limited number of genes related to lipid biosynthesis, and both species lack the fatty acid synthase gene, in line with the known requirement of these yeasts to assimilate lipids from the host. Malassezia species do not appear to have many cell wall-localized glycosylphosphatidylinositol (GPI) proteins and lack other cell wall proteins previously identified in other fungi. This is surprising given that in other fungi these proteins have been shown to mediate interactions (e.g., adhesion and biofilm formation) with the host. The genome revealed a complex evolutionary history for an allergen of unknown function, Mala s 7, shown to be encoded by a member of an amplified gene family of secreted proteins. Based on genetic and biochemical studies with the basidiomycete human fungal pathogen Cryptococcus neoformans, we characterized the allergen Mala s 6 as the cytoplasmic cyclophilin A. We further present evidence that M. sympodialis may have the capacity to undergo sexual reproduction and present a model for a pseudobipolar mating system that allows limited recombination between two linked MAT loci.

Importance: Malassezia commensal yeasts are associated with a number of skin disorders. The previously published genome of M. globosa provided some of the first insights into Malassezia biology and its involvement in dandruff. Here, we present the genome of M. sympodialis, frequently isolated from patients with atopic eczema and healthy individuals. We combined comparative genomics with sequencing and functional characterization of specific genes in a population of clinical isolates and in closely related model systems. Our analyses provide insights into the evolution of allergens related to atopic eczema and the evolutionary trajectory of the machinery for sexual reproduction and meiosis. We hypothesize that M. sympodialis may undergo sexual reproduction, which has important implications for the understanding of the life cycle and virulence potential of this medically important yeast. Our findings provide a foundation for the development of genetic and genomic tools to elucidate host-microbe interactions that occur on the skin and to identify potential therapeutic targets.
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http://dx.doi.org/10.1128/mBio.00572-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3560662PMC
January 2013

The genomic landscape of hypodiploid acute lymphoblastic leukemia.

Nat Genet 2013 Mar 20;45(3):242-52. Epub 2013 Jan 20.

Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

The genetic basis of hypodiploid acute lymphoblastic leukemia (ALL), a subtype of ALL characterized by aneuploidy and poor outcome, is unknown. Genomic profiling of 124 hypodiploid ALL cases, including whole-genome and exome sequencing of 40 cases, identified two subtypes that differ in the severity of aneuploidy, transcriptional profiles and submicroscopic genetic alterations. Near-haploid ALL with 24-31 chromosomes harbor alterations targeting receptor tyrosine kinase signaling and Ras signaling (71%) and the lymphoid transcription factor gene IKZF3 (encoding AIOLOS; 13%). In contrast, low-hypodiploid ALL with 32-39 chromosomes are characterized by alterations in TP53 (91.2%) that are commonly present in nontumor cells, IKZF2 (encoding HELIOS; 53%) and RB1 (41%). Both near-haploid and low-hypodiploid leukemic cells show activation of Ras-signaling and phosphoinositide 3-kinase (PI3K)-signaling pathways and are sensitive to PI3K inhibitors, indicating that these drugs should be explored as a new therapeutic strategy for this aggressive form of leukemia.
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http://dx.doi.org/10.1038/ng.2532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3919793PMC
March 2013
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