| 1. |
- Lundgren, Markus, et al.
(författare)
-
Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
-
Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
|
|
| 2. |
|
|
| 3. |
- Haghighi, Mona, et al.
(författare)
-
A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study
- 2016
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.
|
|
| 4. |
- Johnson, Randi K., et al.
(författare)
-
Metabolite-related dietary patterns and the development of islet autoimmunity
- 2019
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- The role of diet in type 1 diabetes development is poorly understood. Metabolites, which reflect dietary response, may help elucidate this role. We explored metabolomics and lipidomics differences between 352 cases of islet autoimmunity (IA) and controls in the TEDDY (The Environmental Determinants of Diabetes in the Young) study. We created dietary patterns reflecting pre-IA metabolite differences between groups and examined their association with IA. Secondary outcomes included IA cases positive for multiple autoantibodies (mAb+). The association of 853 plasma metabolites with outcomes was tested at seroconversion to IA, just prior to seroconversion, and during infancy. Key compounds in enriched metabolite sets were used to create dietary patterns reflecting metabolite composition, which were then tested for association with outcomes in the nested case-control subset and the full TEDDY cohort. Unsaturated phosphatidylcholines, sphingomyelins, phosphatidylethanolamines, glucosylceramides, and phospholipid ethers in infancy were inversely associated with mAb+ risk, while dicarboxylic acids were associated with an increased risk. An infancy dietary pattern representing higher levels of unsaturated phosphatidylcholines and phospholipid ethers, and lower sphingomyelins was protective for mAb+ in the nested case-control study only. Characterization of this high-risk infant metabolomics profile may help shape the future of early diagnosis or prevention efforts. © 2019, The Author(s).
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Smith, Laura B., et al.
(författare)
-
Psychological manifestations of celiac disease autoimmunity in young children
- 2017
-
Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 0031-4005 .- 1098-4275. ; 139:3
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Psychological symptoms can be associated with celiac disease; abstract however, this association has not been studied prospectively in a pediatric cohort. We examined mother report of psychological functioning in children persistently positive for tissue transglutaminase autoantibodies (tTGA), defined as celiac disease autoimmunity (CDA), compared with children without CDA in a screening population of genetically at-risk children. We also investigated differences in psychological symptoms based on mothers' awareness of their child's CDA status. METHODS: The Environmental Determinants of Diabetes in the Young study followed 8676 children to identify triggers of type 1 diabetes and celiac disease. Children were tested for tTGA beginning at 2 years of age. The Achenbach Child Behavior Checklist assessed child psychological functioning at 3.5 and 4.5 years of age. RESULTS: At 3.5 years, 66 mothers unaware their child had CDA reported more child anxiety and depression, aggressive behavior, and sleep problems than 3651 mothers of children without CDA (all Ps ≤ .03). Unaware-CDA mothers also reported more child anxiety and depression, withdrawn behavior, aggressive behavior, and sleep problems than 440 mothers aware of their child's CDA status (all Ps ≤.04). At 4.5 years, there were no differences. CONCLUSIONS: In 3.5-year-old children, CDA is associated with increased reports of child depression and anxiety, aggressive behavior, and sleep problems when mothers are unaware of their child's CDA status. Mothers' knowledge of their child's CDA status is associated with fewer reports of psychological symptoms, suggesting that awareness of the child's tTGA test results affects reporting of symptoms.
|
|
| 8. |
- Törn, Carina, et al.
(författare)
-
Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study
- 2016
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- A total of 15 SNPs within complement genes and present on the ImmunoChip were analyzed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. A total of 5474 subjects were followed from three months of age until islet autoimmunity (IA: n = 413) and the subsequent onset of type 1 diabetes (n = 115) for a median of 73 months (IQR 54-91). Three SNPs within ITGAM were nominally associated (p < 0.05) with IA: rs1143678 [Hazard ratio; HR 0.80; 95% CI 0.66-0.98; p = 0.032], rs1143683 [HR 0.80; 95% CI 0.65-0.98; p = 0.030] and rs4597342 [HR 1.16; 95% CI 1.01-1.32; p = 0.041]. When type 1 diabetes was the outcome, in DR3/4 subjects, there was nominal significance for two SNPs: rs17615 in CD21 [HR 1.52; 95% CI 1.05-2.20; p = 0.025] and rs4844573 in C4BPA [HR 0.63; 95% CI 0.43-0.92; p = 0.017]. Among DR4/4 subjects, rs2230199 in C3 was significantly associated [HR 3.20; 95% CI 1.75-5.85; p = 0.0002, uncorrected] a significance that withstood Bonferroni correction since it was less than 0.000833 (0.05/60) in the HLA-specific analyses. SNPs within the complement genes may contribute to IA, the first step to type 1 diabetes, with at least one SNP in C3 significantly associated with clinically diagnosed type 1 diabetes.
|
|
| 9. |
- van Hooren, Luuk, et al.
(författare)
-
Agonistic CD40 therapy induces tertiary lymphoid structures but impairs responses to checkpoint blockade in glioma.
- 2021
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Gliomas are brain tumors characterized by an immunosuppressive microenvironment. Immunostimulatory agonistic CD40 antibodies (αCD40) are in clinical development for solid tumors, but are yet to be evaluated for glioma. Here, we demonstrate that systemic delivery of αCD40 in preclinical glioma models induces the formation of tertiary lymphoid structures (TLS) in proximity of meningeal tissue. In treatment-naïve glioma patients, the presence of TLS correlates with increased T cell infiltration. However, systemic delivery of αCD40 induces hypofunctional T cells and impairs the response to immune checkpoint inhibitors in pre-clinical glioma models. This is associated with a systemic induction of suppressive CD11b+ B cells post-αCD40 treatment, which accumulate in the tumor microenvironment. Our work unveils the pleiotropic effects of αCD40 therapy in glioma and reveals that immunotherapies can modulate TLS formation in the brain, opening up for future opportunities to regulate the immune response.
|
|
| 10. |
- Ytreberg, Agnes, et al.
(författare)
-
God havsmiljö 2020 : Marin strategi för Nordsjön och Östersjön Del 3: Övervakningsprogram
- 2014
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Havsmiljöförordningens övergripande mål är att upprätthålla eller uppnå en god miljöstatus i de svenska förvaltningsområdena Nordsjön och Östersjön till år 2020. En av uppgifterna i den första förvaltningsperioden är att fastställa övervakningsprogram.God miljöstatus baseras på ett ramverk av så kallade deskriptorer som anges i havsmiljödirektivet, det vill säga det EU-direktiv som i Sverige genomförs genom havsmiljöförordningen. Deskriptorerna beskriver god miljöstatus på en övergripande nivå för elva temaområden. Till varje deskriptor hör en rad kriterier som anger vad som ska ingå i en bedömning av miljöstatus. Utifrån de elva deskriptorerna har Sverige fastställt 13 övervakningsprogram. Sex program utgår ifrån olika biodiversitetsteman som berörs av en upp till tre deskriptorer, medan de övriga sju programmen utgår ifrån de deskriptorer som är mer inriktade mot belastning och miljöförändring.För varje program har ett antal underprogram föreslagits baserat på den nuvarande övervakningen och/eller planerad övervakning. Övervakning som ingår i programmen ska vara pågående och data ska vara tillgängliga. I programmen ingår nationell och regional miljöövervakning inklusive verksamhetsutövares recipientkontroll. Dessutom ingår annan typ av datainsamling som till exempel inventeringar av tumlare och uppgifter om omfattningen av mänskliga aktiviteter som orsakar belastning och miljöförändringar. Enligt havsmiljödirektivet ska övervakningen fånga upp tillstånd och miljöförändringar, belastning och omfattning av aktiviteterna som orsakar belastningen samt effekter av åtgärder. Eftersom nästa steg i havsförvaltningscykeln är att fastställa åtgärdsprogram kommer övervakning för att följa upp åtgärder att läggas till övervakningsprogrammen först under nästa förvaltningscykel.I beskrivningarna av programmen framgår hur den nuvarande övervakningen motsvarar de krav som ställs på dataunderlag genom havsmiljödirektivets bilaga III samt genom deskriptorer, kriterier, indikatorer och beslutade miljökvalitetsnormer. I dagens övervakning saknas bland annat tillräcklig övervakning för uppföljning av livsmiljöers tillstånd och utbredning. För marint avfall, buller och främmande arter saknas nationellt samordnad övervakning, men det görs regionala insatser och ett antal projekt har genomförts eller påbörjats för att öka kunskapen om hur övervakning bäst ska utformas. För de program som har pågående övervakning beskrivs utvecklingsbehoven för att förbättra underlaget för de återkommande tillståndsbedömningarna.Övervakningsprogrammet som fastställs under 2014 utgör således inte ett fast program för kunskapsinhämtning. Bristerna kommer att beaktas i det fortsatta genomförandet av havsmiljöförordningen där utveckling av indikatorer och övervakning kommer att ske kontinuerligt.
|
|
| 11. |
- Abayneh, Sisay A, et al.
(författare)
-
Sensitivity of HIV-1 primary isolates to human anti-CD40 antibody-mediated suppression is related to co-receptor use
- 2008
-
Ingår i: AIDS Research and Human Retroviruses. - : Mary Ann Liebert Inc. - 1931-8405 .- 0889-2229. ; 24:3, s. 447-452
-
Tidskriftsartikel (refereegranskat)abstract
- The effect of CD40 ligation on infection by HIV-1 primary isolates with different R5 phenotypes was evaluated with a novel set of anti-CD40 monoclonal antibodies originating from a human phage display library. Five human monoclonal anti-CD40 antibodies of IgG1 subtype characterized by the ability to activate B cells via CD40 were tested for induction of the CC-chemokines RANTES and MIP-1alpha and inhibition of HIV-1 replication in primary monocyte-derived macrophages (MDM). All activating anti-CD40 antibodies were able to induce CC-chemokines in MDM. We chose the most potent antibody, clone B44, for further experiments. This antibody had a suppressive effect on HIV-1 isolates of the R5 phenotype with limited use of CCR5/CXCR4 chimeric receptors. In comparison, HIV-1 isolates with broader use of CCR5/CXCR4 chimeric receptors or with CXCR4 use were less sensitive to anti-CD40-induced suppression. The results indicate that HIV-1 replication is inhibited by human anti-CD40 monoclonal antibodies through the mechanism of CC-chemokine induction. This effect is thus restricted to HIV-1 isolates sensitive to inhibition by CC-chemokines.
|
|
| 12. |
- Adman, Per, et al.
(författare)
-
171 forskare: ”Vi vuxna bör också klimatprotestera”
- 2019
-
Ingår i: Dagens nyheter (DN debatt). - Stockholm. - 1101-2447.
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DN DEBATT 26/9. Vuxna bör följa uppmaningen från ungdomarna i Fridays for future-rörelsen och protestera eftersom det politiska ledarskapet är otillräckligt. Omfattande och långvariga påtryckningar från hela samhället behövs för att få de politiskt ansvariga att utöva det ledarskap som klimatkrisen kräver, skriver 171 forskare i samhällsvetenskap och humaniora.
|
|
| 13. |
- Alexandersson, Erik, et al.
(författare)
-
Whole gene family expression and drought stress regulation of aquaporins
- 2005
-
Ingår i: Plant Molecular Biology. - : Springer Science and Business Media LLC. - 1573-5028 .- 0167-4412. ; 59:3, s. 469-484
-
Tidskriftsartikel (refereegranskat)abstract
- Since many aquaporins (AQPs) act as water channels, they are thought to play an important role in plant water relations. It is therefore of interest to study the expression patterns of AQP isoforms in order to further elucidate their involvement in plant water transport. We have monitored the expression patterns of all 35 Arabidopsis AQPs in leaves, roots and flowers by cDNA microarrays, specially designed for AQPs, and by quantitative real-time reverse transcriptase PCR (Q-RT-PCR). This showed that many AQPs are pre-dominantly expressed in either root or flower organs, whereas no AQP isoform seem to be leaf specific. Looking at the AQP subfamilies, most plasma membrane intrinsic proteins (PIPs) and some tonoplast intrinsic proteins (TIPs) have a high level of expression, while NOD26-like proteins (NIPs) are present at a much lower level. In addition, we show that PIP transcripts are generally down-regulated upon gradual drought stress in leaves, with the exception of AtPIP1;4 and AtPIP2;5, which are up-regulated. AtPIP2;6 and AtSIP1;1 are constitutively expressed and not significantly affected by the drought stress. The transcriptional down-regulation of PIP genes upon drought stress could also be observed on the protein level.
|
|
| 14. |
- Alijagic, Andi, 1992-, et al.
(författare)
-
Particle Safety Assessment in Additive Manufacturing : From Exposure Risks to Advanced Toxicology Testing.
- 2022
-
Ingår i: Frontiers in Toxicology. - : Frontiers Media S.A.. - 2673-3080. ; 4
-
Forskningsöversikt (refereegranskat)abstract
- Additive manufacturing (AM) or industrial three-dimensional (3D) printing drives a new spectrum of design and production possibilities; pushing the boundaries both in the application by production of sophisticated products as well as the development of next-generation materials. AM technologies apply a diversity of feedstocks, including plastic, metallic, and ceramic particle powders with distinct size, shape, and surface chemistry. In addition, powders are often reused, which may change the particles' physicochemical properties and by that alter their toxic potential. The AM production technology commonly relies on a laser or electron beam to selectively melt or sinter particle powders. Large energy input on feedstock powders generates several byproducts, including varying amounts of virgin microparticles, nanoparticles, spatter, and volatile chemicals that are emitted in the working environment; throughout the production and processing phases. The micro and nanoscale size may enable particles to interact with and to cross biological barriers, which could, in turn, give rise to unexpected adverse outcomes, including inflammation, oxidative stress, activation of signaling pathways, genotoxicity, and carcinogenicity. Another important aspect of AM-associated risks is emission/leakage of mono- and oligomers due to polymer breakdown and high temperature transformation of chemicals from polymeric particles, both during production, use, and in vivo, including in target cells. These chemicals are potential inducers of direct toxicity, genotoxicity, and endocrine disruption. Nevertheless, understanding whether AM particle powders and their byproducts may exert adverse effects in humans is largely lacking and urges comprehensive safety assessment across the entire AM lifecycle-spanning from virgin and reused to airborne particles. Therefore, this review will detail: 1) brief overview of the AM feedstock powders, impact of reuse on particle physicochemical properties, main exposure pathways and protective measures in AM industry, 2) role of particle biological identity and key toxicological endpoints in the particle safety assessment, and 3) next-generation toxicology approaches in nanosafety for safety assessment in AM. Altogether, the proposed testing approach will enable a deeper understanding of existing and emerging particle and chemical safety challenges and provide a strategy for the development of cutting-edge methodologies for hazard identification and risk assessment in the AM industry.
|
|
| 15. |
- Alsanius, Beatrix, et al.
(författare)
-
The power of light from a non-phototrophic perspective: a phyllosphere dilemma
- 2024
-
Ingår i: Frontiers in Photobiology. - 2813-8228. ; 2
-
Tidskriftsartikel (refereegranskat)abstract
- Plants and crop stands are considered holobionts, colonized by both autotrophic and by non-phototrophic heterotrophic microbiota. The dilemma in the exisiting body of studies is that the focus is primarily directed towards environmental specificties relevant for phototrophic organisms (predominantly plants), but does not take into account non-phototrophs. By definition, non-phototrophic heterotrophic bacteria do not use light as an energy source. Light energy and wavelength are rather used as a signal that can provoke shifts in both their metabolism and microbial lifestyle. Reaction and recovery time can vary between organisms and is dependent on the organism’s physiological stage. The length of the lighting event affects the energy an organism is exposed to. We argue that to obtain a deeper and more distinct understanding of light exposure (irradiance, exposure length), quantity (light intensity), and quality (wavelength/spectral distribution, bandwidth at full-width half-maximum) related mechanisms on non-phototrophic bacteria in the phyllosphere, the light environment needs to be further strictly characterized. This includes information on the actual energy hitting planktonic or sessile non-phototrophic bacteria resident on and inside plants aboveground. Mapping the light environment in ecosystems aids in unraveling light-phyllosphere interactions and strengthens their transdisciplinary character. This issue is fundamental in order to revisit and repeat others’ experimental approaches and findings but also to be able to translate findings into further action.
|
|
| 16. |
- Alsanius, Beatrix, et al.
(författare)
-
The two sides of the coin: sustainability and controlled environment horticulture
- 2023
-
Ingår i: Acta Horticulturae. - 0567-7572 .- 2406-6168. ; , s. 427-438
-
Konferensbidrag (refereegranskat)abstract
- Sustainability, although already outlined in the late 1980s, has evolved into a game changer in the discourse of production systems. This review puts a finger on the pulse of horticultural research with respect to i) the 17 UN sustainable development goals (SDGs) and identifies areas (targets) directly or indirectly providing benefits and trade-offs based on scrutiny of 169 targets and to ii) grouping outputs of a systematic literature search with respect to basic sustainability and resilience criteria. Direct and indirect benefits of the SDGs to horticulture were identified within SDG 2 (Zero hunger), 3 (Health and wellbeing), 4 (Quality education), 6 (Clean water and sanitation), 7 (Clean energy) and 9 (Innovation, infrastructure and industry), whereas SDGs that benefit from horticulture within the SDGs 2, 4, 6, 9, 12 (Responsible consumption and production) and 13 (Climate action). 104 publications were extracted and 53 of these were found eligible for the systematic literature analysis based on the criteria for exclusion and inclusion. Few publications considered the concept of resilience, in terms of absorbance, recovery and adaptation to disturbances. Meanwhile, the majority of publications focused on sustainability, but rather referred to the term than integrated sustainability as a concept. Studies involving life cycle analysis highlight the strong energy dependence of high-tech horticulture, underlining the interactivities with SDG7. Fine-tuning of input means and measures were prioritized to the detriment of holistic approaches. The shift in the global challenges framework requests a shift in perspective of horticulture research. To holistically focus on the food system-horticulture-SDG link, an agenda for research on high-tech horticulture was established. Current pandemic and geopolitical disturbances urge for a stronger engagement of resilience research in horticulture.
|
|
| 17. |
- Andersson, Magnus, et al.
(författare)
-
Fiskbestånd och miljö i hav och sötvatten : Resurs- och miljööversikt 2012
- 2012
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Detta är den nionde utgåvan av den samlade översikten över fisk- och kräftdjursbeståndens status i våra vatten. Kunskap om fiskbestånden och miljön är en förutsättning för att utnyttjandet av fiskresurserna skall bli bärkraftigt. För svenska vattenområden beskrivs miljöutvecklingen i ett ekosystemsperspektiv, dels för att tydliggöra fiskens ekologiska roll och beskriva yttre miljöfaktorer som påverkar fiskbestånden, dels för att belysa fiskets effekter på miljön.Fiskbestånd och miljö i hav och sötvatten är utarbetad av Sveriges lantbruksuniversitet (SLU), Institutionen för akvatiska resurser (SLU Aqua), på uppdrag av Havs- och vattenmyndigheten. Rapporten sammanfattar utveckling och beståndsstatus för de kommersiellt viktigaste fisk- och kräftdjursarterna i våra vatten. Bedömningar och förvaltningsråd är baserade på Internationella Havsforskningsrådets (ICES) rådgivning, SLU Aquas nationella och regionala provfiskedata, samt yrkesfiskets rapportering.
|
|
| 18. |
- Assenhöj, Maria, et al.
(författare)
-
Protein interaction, monocyte toxicity and immunogenic properties of cerium oxide crystals with 5% or 14% gadolinium, cobalt oxide and iron oxide nanoparticles–an interdisciplinary approach
- 2021
-
Ingår i: Nanotoxicology. - : Taylor and Francis Ltd.. - 1743-5390 .- 1743-5404. ; 15:8, s. 1035-1038
-
Tidskriftsartikel (refereegranskat)abstract
- Metal oxide nanoparticles are widely used in both consumer products and medical applications, but the knowledge regarding exposure-related health effects is limited. However, it is challenging to investigate nanoparticle interaction processes with biological systems. The overall aim of this project was to improve the possibility to predict exposure-related health effects of metal oxide nanoparticles through interdisciplinary collaboration by combining workflows from the pharmaceutical industry, nanomaterial sciences, and occupational medicine. Specific aims were to investigate nanoparticle-protein interactions and possible adverse immune reactions. Four different metal oxide nanoparticles; CeOx nanocrystals with 5% or 14% Gd, Co3O4, and Fe2O3, were characterized by dynamic light scattering and high-resolution transmission electron microscopy. Nanoparticle-binding proteins were identified and screened for HLA-binding peptides in silico. Monocyte interaction with nanoparticle–protein complexes was assessed in vitro. Herein, for the first time, immunogenic properties of nanoparticle-binding proteins have been characterized. The present study indicates that especially Co3O4-protein complexes can induce both ‘danger signals’, verified by the production of inflammatory cytokines and simultaneously bind autologous proteins, which can be presented as immunogenic epitopes by MHC class II. The clinical relevance of these findings should be further evaluated to investigate the role of metal oxide nanoparticles in the development of autoimmune disease. The general workflow identified experimental difficulties, such as nanoparticle aggregate formation and a lack of protein-free buffers suitable for particle characterization, protein analyses, as well as for cell studies. This confirms the importance of future interdisciplinary collaborations. © 2021 The Author(s).
|
|
| 19. |
- Bigdeli, Narmin, 1974, et al.
(författare)
-
Superior Osteogenic Capacity of Human Embryonic Stem Cells Adapted to Matrix-Free Growth Compared to Human Mesenchymal Stem Cells.
- 2010
-
Ingår i: Tissue engineering. Part A. - : Mary Ann Liebert Inc. - 1937-335X .- 1937-3341. ; 16:11, s. 3427-3440
-
Tidskriftsartikel (refereegranskat)abstract
- Human mesenchymal stem cells (hMSCs) represent a promising source of cells for bone tissue engineering. However, their low frequencies and limited proliferation restrict their clinical utility. An alternative is the use of human embryonic stem cells (hESCs), but labor-intensive expansion with the need for coating support limits their clinical use. We have previously derived a cell line from hESCs denoted matrix-free growth (MFG)-hESC that are independent of coating support for expansion, and we here compare its osteogenic capacity to that of hMSCs. Microarray analysis of hMSCs and MFG-hESCs revealed differential expression of genes involved in ossification. MFG-hESCs have significantly higher expression of secreted phosphoprotein 1 (SPP1) during osteogenic differentiation, whereas the opposite was true for alkaline phosphatase (ALPL), transforming growth factor, beta 1 (TGFB2), runt-related transcription factor 2 (RUNX2), and forkhead box C1 (FOXC1), as well as the activity of the ALPL enzyme, demonstrating that these two cell types differentiate into the osteogenic lineage using different signaling pathways. von Kossa staining, time-of-flight secondary ion mass spectrometry, and measurement of calcium and phosphate in the extracellular matrix demonstrated a superior ability of the MFG-hESCs to produce a mineralized matrix compared to hMSCs. The superior ability of the MFG-hESCs to form mineralized matrix compared to hMSCs demonstrates that MFG-hESCs are a promising alternative to the use of adult stem cells in future bone regenerative applications.
|
|
| 20. |
- Bigdeli, Narmin, 1974, et al.
(författare)
-
Upregulation of adhesion molecules sustains matrix-free growth of human embryonic stem cells
- 2018
-
Ingår i: Open Stem Cell Journal. - : Bentham Science Publishers Ltd.. - 1876-8938. ; 5:1, s. 14-30
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Despite recent advances in culture techniques for undifferentiated human Embryonic Stem Cells (hESCs), further improvements are required to facilitate research and translation of these cells in clinical settings. We have previously derived hESC lines that can be cultured in their undifferentiated state on regular plastic culture dishes, without the need for feeder cells or other coating supports, denoted Matrix-Free Growth hESCs (MFG-hESCs). Objective: In this study, we further characterize and compare MFG-hESCs to hESCs in order to understand the molecular differences responsible for the unique ability of MFG-hESCs. Results: Microarray analysis demonstrated that MFG-hESCs highly resemble feeder-cultured hESCs in global gene expression profile. Two identified groups of genes with differential expression were those encoding for ribosomal proteins and attachment proteins, such as the RGD (Arg-Gly-Asp)-associated proteins. Real-time PCR and flow cytometry corroborated the microarray results. Culture of MFG-hESCs in the presence of RGD peptides resulted in decreased attachment ability compared to cells cultured in the presence of RGES (Arg-Gly-Asp-Ser) peptides. Conclusion: This study demonstrates that MFG-hESC lines overexpress cell attachment proteins but retain the typical characteristics of undifferentiated feeder-cultured hESCs. The ability to culture high-quality pluripotent stem cells in feeder-and matrix-free conditions creates a new opportunities for their large-scale manufacturing for experimental research and translational applications. © 2018 Bigdeli et al.
|
|
| 21. |
- Bray, Lucy, et al.
(författare)
-
Developing rights-based standards for children having tests, treatments, examinations and interventions : using a collaborative, multi-phased, multi-method and multi-stakeholder approach to build consensus
- 2023
-
Ingår i: European Journal of Pediatrics. - : Springer Nature. - 0340-6199 .- 1432-1076.
-
Tidskriftsartikel (refereegranskat)abstract
- Children continue to experience harm when undergoing clinical procedures despite increased evidence of the need to improve the provision of child-centred care. The international ISupport collaboration aimed to develop standards to outline and explain good procedural practice and the rights of children within the context of a clinical procedure. The rights-based standards for children undergoing tests, treatments, investigations, examinations and interventions were developed using an iterative, multi-phased, multi-method and multi-stakeholder consensus building approach. This consensus approach used a range of online and face to face methods across three phases to ensure ongoing engagement with multiple stakeholders. The views and perspectives of 203 children and young people, 78 parents and 418 multi-disciplinary professionals gathered over a two year period (2020–2022) informed the development of international rights-based standards for the care of children having tests, treatments, examinations and interventions. The standards are the first to reach international multi-stakeholder consensus on definitions of supportive and restraining holds.Conclusion: This is the first study of its kind which outlines international rights-based procedural care standards from multi-stakeholder perspectives. The standards offer health professionals and educators clear evidence-based tools to support discussions and practice changes to challenge prevailing assumptions about holding or restraining children and instead encourage a focus on the interests and rights of the child.What is Known:• Children continue to experience short and long-term harm when undergoing clinical procedures despite increased evidence of the need to improve the provision of child-centred care.• Professionals report uncertainty and tensions in applying evidence-based practice to children’s procedural care. What is New:• This is the first study of its kind which has developed international rights-based procedural care standards from multi-stakeholder perspectives.• The standards are the first to reach international multi-stakeholder consensus on definitions of supportive and restraining holds.
|
|
| 22. |
- Broesby-Olsen, Sigurd, et al.
(författare)
-
Multidisciplinary Management of Mastocytosis : Nordic Expert Group Consensus
- 2016
-
Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 96:5
-
Tidskriftsartikel (refereegranskat)abstract
- Mastocytosis is a heterogeneous group of diseases defined by an increased number and accumulation of mast cells, and often also by signs and symptoms of mast cell activation. Disease subtypes range from indolent to rare aggressive forms. Mastocytosis affects people of all ages and has been considered rare; however, it is probably underdiagnosed with potential severe implications. Diagnosis can be challenging and symptoms may be complex and involve multiple organ-systems. In general it is advised that patients should be referred to centres with experience in the disease offering an individualized, multidisciplinary approach. We present here consensus recommendations from a Nordic expert group for the diagnosis and general management of patients with mastocytosis.
|
|
| 23. |
|
|
| 24. |
- Cappellini, Francesca, et al.
(författare)
-
Dry Generation of CeO2 Nanoparticles and Deposition onto a Co-Culture of A549 and THP-1 Cells in Air-Liquid Interface-Dosimetry Considerations and Comparison to Submerged Exposure
- 2020
-
Ingår i: Nanomaterials. - : MDPI AG. - 2079-4991. ; 10:4
-
Tidskriftsartikel (refereegranskat)abstract
- Relevant in vitro assays that can simulate exposure to nanoparticles (NPs) via inhalation are urgently needed. Presently, the most common method employed is to expose lung cells under submerged conditions, but the cellular responses to NPs under such conditions might differ from those observed at the more physiological air-liquid interface (ALI). The aim of this study was to investigate the cytotoxic and inflammatory potential of CeO2 NPs (NM-212) in a co-culture of A549 lung epithelial cells and differentiated THP-1 cells in both ALI and submerged conditions. Cellular dose was examined quantitatively using inductively coupled plasma mass spectrometry (ICP-MS). The role of serum and LPS-priming for IL-1 beta release was further tested in THP-1 cells in submerged exposure. An aerosol of CeO2 NPs was generated by using the PreciseInhale (R) system, and NPs were deposited on the co-culture using XposeALI (R). No or minor cytotoxicity and no increased release of inflammatory cytokines (IL-1 beta, IL-6, TNF alpha, MCP-1) were observed after exposure of the co-culture in ALI (max 5 mu g/cm(2)) or submerged (max 22 mu g/cm(2)) conditions. In contrast, CeO2 NPs cause clear IL-1 beta release in monocultures of macrophage-like THP-1, independent of the presence of serum and LPS-priming. This study demonstrates a useful approach for comparing effects at various in-vitro conditions.
|
|
| 25. |
|
|
| 26. |
- Chen, Chao, et al.
(författare)
-
Epigenome-wide gene-age interaction analysis reveals reversed effects of PRODH DNA methylation on survival between young and elderly early-stage NSCLC patients
- 2020
-
Ingår i: Aging. - : Impact Journals, LLC. - 1945-4589. ; 12:11, s. 10642-10662
-
Tidskriftsartikel (refereegranskat)abstract
- DNA methylation changes during aging, but it remains unclear whether the effect of DNA methylation on lung cancer survival varies with age. Such an effect could decrease prediction accuracy and treatment efficacy. We performed a methylation-age interaction analysis using 1,230 early-stage lung adenocarcinoma patients from five cohorts. A Cox proportional hazards model was used to investigate lung adenocarcinoma and squamous cell carcinoma patients for methylation-age interactions, which were further confirmed in a validation phase. We identified one adenocarcinoma-specific CpG probe, cg14326354PRODH, with effects significantly modified by age (HRinteraction = 0.989; 95% CI: 0.986-0.994; P = 9.18×10-7). The effect of low methylation was reversed for young and elderly patients categorized by the boundary of 95% CI standard (HRyoung = 2.44; 95% CI: 1.26-4.72; P = 8.34×10-3; HRelderly = 0.58; 95% CI: 0.42-0.82; P = 1.67×10-3). Moreover, there was an antagonistic interaction between low cg14326354PRODH methylation and elderly age (HRinteraction = 0.21; 95% CI: 0.11-0.40; P = 2.20×10-6). In summary, low methylation of cg14326354PRODH might benefit survival of elderly lung adenocarcinoma patients, providing new insight to age-specific prediction and potential drug targeting.
|
|
| 27. |
- Chen, Jiajin, et al.
(författare)
-
A trans-omics assessment of gene–gene interaction in early-stage NSCLC
- 2023
-
Ingår i: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 17:1, s. 173-187
-
Tidskriftsartikel (refereegranskat)abstract
- Epigenome-wide gene–gene (G × G) interactions associated with non-small-cell lung cancer (NSCLC) survival may provide insights into molecular mechanisms and therapeutic targets. Hence, we proposed a three-step analytic strategy to identify significant and robust G × G interactions that are relevant to NSCLC survival. In the first step, among 49 billion pairs of DNA methylation probes, we identified 175 775 G × G interactions with PBonferroni ≤ 0.05 in the discovery phase of epigenomic analysis; among them, 15 534 were confirmed with P ≤ 0.05 in the validation phase. In the second step, we further performed a functional validation for these G × G interactions at the gene expression level by way of a two-phase (discovery and validation) transcriptomic analysis, and confirmed 25 significant G × G interactions enriched in the 6p21.33 and 6p22.1 regions. In the third step, we identified two G × G interactions using the trans-omics analysis, which had significant (P ≤ 0.05) epigenetic cis-regulation of transcription and robust G × G interactions at both the epigenetic and transcriptional levels. These interactions were cg14391855 × cg23937960 (βinteraction = 0.018, P = 1.87 × 10−12), which mapped to RELA × HLA-G (βinteraction = 0.218, P = 8.82 × 10−11) and cg08872738 × cg27077312 (βinteraction = −0.010, P = 1.16 × 10−11), which mapped to TUBA1B × TOMM40 (βinteraction =−0.250, P = 3.83 × 10−10). A trans-omics mediation analysis revealed that 20.3% of epigenetic effects on NSCLC survival were significantly (P = 0.034) mediated through transcriptional expression. These statistically significant trans-omics G × G interactions can also discriminate patients with high risk of mortality. In summary, we identified two G × G interactions at both the epigenetic and transcriptional levels, and our findings may provide potential clues for precision treatment of NSCLC.
|
|
| 28. |
|
|
| 29. |
- Dahl, Maria, et al.
(författare)
-
Correction of pathology in mice displaying Gaucher disease type 1 by a clinically-applicable lentiviral vector
- 2021
-
Ingår i: Molecular Therapy - Methods and Clinical Development. - : Elsevier BV. - 2329-0501. ; 20, s. 312-323
-
Tidskriftsartikel (refereegranskat)abstract
- This study evaluates a clinically applicable lentiviral vector for treatment of Gaucher disease type 1. Hematopoietic stem cells transduced with the vector and transplanted into a mouse model successfully halted or reversed pathology. These data were used as proof-of-concept for regulatory filing enabling the commencement of an international phase 1/2 clinical trial.
|
|
| 30. |
- Darlison, Julia, et al.
(författare)
-
Leaf mineral content govern microbial community structure in the phyllosphere of spinach (Spinacia oleracea) and rocket (Diplotaxis tenuifolia)
- 2019
-
Ingår i: Science of the Total Environment. - : Elsevier BV. - 1879-1026 .- 0048-9697. ; 675, s. 501-512
-
Tidskriftsartikel (refereegranskat)abstract
- The plant microbiome is an important factor for plant health and productivity. While the impact of nitrogen (N) availability for plant growth and development is well established, its influence on the microbial phyllosphere community structure is unknown. We hypothesize that nitrogen impacts the growth and abundance of several microorganisms on the leaf surface. The bacterial and fungal communities of baby leaf spinach (Spinacia oleracea), and rocket (Diplotaxis tenuifolia) were investigated in a field trial for two years in a commercial setting. Nitrogen fertilizer was tested in four doses (basic nitrogen, basic + suboptimal, basic + commercial, basic + excess) with six replicates in each. Culture-independent (Illumina sequencing) and culture-dependent (viable count and identification of bacterial isolates) community studies were combined with monitoring of plant physiology and site weather conditions. This study found that alpha diversity of bacterial communities decreased in response to increasing nitrogen fertilizer dose, whereas viable counts showed no differences. Correspondingly, fungal communities of the spinach phyllosphere showed a decreasing pattern, whereas the decreasing diversity of fungal communities of rocket was not significant. Plant species and effects of annual variations on microbiome structure were observed for bacterial and fungal communities on both spinach and rocket. This study provides novel insights on the impact of nitrogen fertilizer regime on a nutrient scarce habitat, the phyllosphere.
|
|
| 31. |
- Davila, Maria E., et al.
(författare)
-
Perturbation of Ge(111) and Si(111)root 3 alpha-Sn surfaces by adsorption of dopants
- 2006
-
Ingår i: Surface Science. - : Elsevier BV. - 0039-6028 .- 1879-2758. ; 600:16, s. 3154-3159
-
Tidskriftsartikel (refereegranskat)abstract
- We test the response of the root 3 x root 3 alpha reconstructions formed by 1/3 monolayer of tin adatoms on silicon and germanium (111) surfaces upon doping with electrons or holes, using potassium or iodine as probes/perturbers of the initial electronic structures. From detailed synchrotron radiation photoelectron spectroscopy studies we show that doping with either electrons or holes plays a complimentary role on the Si and Ge surfaces and, especially, leads to complete conversion of the Sn 4d two-component spectra into single line shapes. We find that the low binding energy component of the Sn core level for both Si and Ge surfaces corresponds to Sn adatoms with higher electronic charge, than the Sn adatoms that contribute to the core level high binding energy signal. This could be analyzed as Sn adatoms with different valence state.
|
|
| 32. |
- de Peppo, Giuseppe Maria, 1981, et al.
(författare)
-
Free-form-fabricated commercially-pure Ti and Ti6Al4V porous scaffolds support the growth of human embryonic stem cell-derived medsodermal progenitors
- 2012
-
Ingår i: The Scientific World Journal. - : Hindawi Limited. - 2356-6140 .- 1537-744X. ; 2012
-
Tidskriftsartikel (refereegranskat)abstract
- Commercially-pure titanium (cp-Ti) and the titanium-aluminum-vanadium alloy (Ti6Al4V) are widely used as reconstructive implants for skeletal engineering applications, due to their good mechanical properties, biocompatibility and ability to integrate with the surrounding bone. Electron beam melting technology (EBM) allows the fabrication of customized implants with tailored mechanical properties and high potential in the clinical practice. In order to augment the interaction with the biological tissue, stem cells have recently been combined with metallic scaffolds for skeletal engineering applications. We previously demonstrated that human embryonic stem cell-derived mesodermal progenitors (hES-MPs) hold a great potential to provide a homogeneous and unlimited supply of cells for bone engineering applications. This study demonstrates the effect of EBM-fabricated cp-Ti and Ti6Al4V porous scaffolds on hES-MPs behavior, in terms of cell attachment, growth and osteogenic differentiation. Displaying different chemical composition but similar surface properties, EBM-fabricated cp-Ti and Ti6Al4V scaffolds supported cell attachment and growth, and did not seem to alter the expression of genes involved in osteogenic differentiation and affect the alkaline phosphatase activity. In conclusion, interfacing hES-MPs to EBM-fabricated scaffolds may represent an interesting strategy for design of third-generation biomaterials, with the potential to promote implant integration in clinical conditions characterized by poor bone quality. Copyright 2012 G. M. de Peppo et al.
|
|
| 33. |
- de Peppo, Giuseppe Maria, 1981, et al.
(författare)
-
Human embryonic mesodermal progenitors highly resemble human mesenchymal stem cells and display high potential for tissue engineering applications.
- 2010
-
Ingår i: Tissue engineering. Part A. - : Mary Ann Liebert Inc. - 1937-335X .- 1937-3341. ; 16:7, s. 2161-82
-
Tidskriftsartikel (refereegranskat)abstract
- Adult stem cells, such as human mesenchymal stem cells (hMSCs), show limited proliferative capacity and, after long-term culture, lose their differentiation capacity and are therefore not an optimal cell source for tissue engineering. Human embryonic stem cells (hESCs) constitute an important new resource in this field, but one major drawback is the risk of tumor formation in the recipients. One alternative is to use progenitor cells derived from hESCs that are more lineage restricted but do not form teratomas. We have recently derived a cell line from hESCs denoted hESC-derived mesodermal progenitors (hES-MPs), and here, using genome-wide microarray analysis, we report that the process of hES-MPs derivation results in a significantly altered expression of hESC characteristic genes to an expression level highly similar to that of hMSCs. However, hES-MPs displayed a significantly higher proliferative capacity and longer telomeres. The hES-MPs also displayed lower expression of HLA class II proteins before and after interferon-gamma treatment, indicating that these cells may somewhat be immunoprivileged and potentially used for HLA-incompatible transplantation. The hES-MPs are thus an appealing alternative to hMSCs in tissue engineering applications and stem-cell-based therapies for mesodermal tissues.
|
|
| 34. |
|
|
| 35. |
- de Peppo, Giuseppe Maria, 1981, et al.
(författare)
-
Osteogenic Potential of Human Mesenchymal Stem Cells and Human Embryonic Stem Cell-Derived Mesodermal Progenitors: A Tissue Engineering Perspective.
- 2010
-
Ingår i: Tissue engineering. Part A. - : Mary Ann Liebert Inc. - 1937-335X .- 1937-3341. ; 16:11, s. 3413-3426
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Human mesenchymal stem cells (hMSCs) are promising candidates for bone engineering and regeneration with a considerable number of experimental successes reported over the last years. However, hMSCs show several limitations for tissue engineering applications, which can be overcome by using human embryonic stem cell-derived mesodermal progenitors (hES-MPs). The aim of this study was to investigate and compare the osteogenic differentiation potential of hMSCs and hES-MPs. Materials and Methods: The osteogenic differentiation and mineralization behavior of both cell types were evaluated at passage 5, 10, 15, and 20. Expression of COL1A1, RUNX2, OPN, and OC was evaluated by reverse transcription (RT)-polymerase chain reaction, whereas mineralization was examined by photospectrometry, von Kossa staining, and time-of-flight secondary ion mass spectrometry. The immunoprofile of both cell types was investigated by flow cytometry. Results: We demonstrated that, under proper stimulation, hES-MPs undergo osteogenic differentiation and exhibit significantly increased mineralization ability compared to hMSCs after protracted expansion. hES-MPs were also found to express lower amount of human leukocyte antigens class II proteins. Conclusions: The high osteogenic ability of hES-MPs, together with low expression of human leukocyte antigens class II, makes these cells an attractive alternative for bulk production of cells for bone engineering applications.
|
|
| 36. |
- de Peppo, Giuseppe Maria, et al.
(författare)
-
Osteogenic response of human mesenchymal stem cells to well-defined nanoscale topography in vitro
- 2014
-
Ingår i: International Journal of Nanomedicine. - 1176-9114 .- 1178-2013. ; 9:1, s. 2499-2515
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Patterning medical devices at the nanoscale level enables the manipulation of cell behavior and tissue regeneration, with topographic features recognized as playing a significant role inthe osseointegration of implantable devices. Methods: In this study, we assessed the ability of titanium-coated hemisphere-like topographic nanostructures of different sizes (approximately 50, 100, and 200 nm) to influence the morphology, proliferation, and osteogenic differentiation of human mesenchymal stem cells (hMSCs). Results: We found that the proliferation and osteogenicdifferentiation of hMSCs was influenced by the size of the underlying structures, suggesting that size variations in topographic features at the nanoscale level, independently of chemistry, can be exploited to control hMSC behavior in a size-dependent fashion. Conclusion: Our studies demonstrate that colloidal lithography, in combination with coating technologies, can be exploited to investigate the cell response to well defined nanoscale topography and to develop next-generation surfaces that guide tissue regeneration and promote implant integration.
|
|
| 37. |
- de Peppo, Giuseppe Maria, 1981, et al.
(författare)
-
Osteogenic response of human mesenchymal stem cells to well-defined nanoscale topography in vitro
- 2014
-
Ingår i: International journal of nanomedicine. - : Informa UK Limited. - 1176-9114 .- 1178-2013. ; 9:1, s. 2499-2515
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Patterning medical devices at the nanoscale level enables the manipulation of cell behavior and tissue regeneration, with topographic features recognized as playing a significant role in the osseointegration of implantable devices. Methods: In this study, we assessed the ability of titanium-coated hemisphere-like topographic nanostructures of different sizes (approximately 50, 100, and 200 nm) to influence the morphology, proliferation, and osteogenic differentiation of human mesenchymal stem cells (hMSCs). Results: We found that the proliferation and osteogenic differentiation of hMSCs was influenced by the size of the underlying structures, suggesting that size variations in topographic features at the nanoscale level, independently of chemistry, can be exploited to control hMSC behavior in a size-dependent fashion. Conclusion: Our studies demonstrate that colloidal lithography, in combination with coating technologies, can be exploited to investigate the cell response to well defined nanoscale topography and to develop next-generation surfaces that guide tissue regeneration and promote implant integration.
|
|
| 38. |
- Diaz Cruz, Maria Araceli, et al.
(författare)
-
Characterization of methylation patterns associated with lifestyle factors and vitamin D supplementation in a healthy elderly cohort from Southwest Sweden
- 2022
-
Ingår i: Scientific Reports. - : Nature Portfolio. - 2045-2322. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Numerous studies have shown that lifestyle factors, such as regular physical activity and vitamin D intake, may remarkably improve overall health and mental wellbeing. This is especially important in older adults whose vitamin D deficiency occurs with a high prevalence. This study aimed to examine the influence of lifestyle and vitamin D on global DNA methylation patterns in an elderly cohort in Southwest of Sweden. We also sought to examine the methylation levels of specific genes involved in vitamin D's molecular and metabolic activated pathways. We performed a genome wide methylation analysis, using Illumina Infinium DNA Methylation EPIC 850kBeadChip array, on 277 healthy individuals from Southwest Sweden at the age of 70-95. The study participants also answered queries on lifestyle, vitamin intake, heart medication, and estimated health. Vitamin D intake did not in general affect methylation patterns, which is in concert with other studies. However, when comparing the group of individuals taking vitamin supplements, including vitamin D, with those not taking supplements, a difference in methylation in the solute carrier family 25 (SCL25A24) gene was found. This confirms a previous finding, where changes in expression of SLC25A24 were associated with vitamin D treatment in human monocytes. The combination of vitamin D intake and high physical activity increased methylation of genes linked to regulation of vitamin D receptor pathway, the Wnt pathway and general cancer processes. To our knowledge, this is the first study detecting epigenetic markers associated with the combined effects of vitamin D supplementation and high physical activity. These results deserve to be further investigated in an extended, interventional study cohort, where also the levels of 25(OH)D3 can be monitored.
|
|
| 39. |
- Diaz Cruz, Maria Araceli, et al.
(författare)
-
Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems
- 2021
-
Ingår i: Open Medicine (Poland). - : De Gruyter Open. - 2391-5463. ; 16:1, s. 640-650
-
Tidskriftsartikel (refereegranskat)abstract
- Nuclear receptors (NRs) are ligand-activated transcription factors that regulate gene expression when bound to specific DNA sequences. Crosstalk between steroid NR systems has been studied for understanding the development of hormone-driven cancers but not to an extent at a genetic level. This study aimed to investigate crosstalk between steroid NRs in conserved intron and exon sequences, with a focus on steroid NRs involved in prostate cancer etiology. For this purpose, we evaluated conserved intron and exon sequences among all 49 members of the NR Superfamily (NRS) and their relevance as regulatory sequences and NR-binding sequences. Sequence conservation was found to be higher in the first intron (35%), when compared with downstream introns. Seventy-nine percent of the conserved regions in the NRS contained putative transcription factor binding sites (TFBS) and a large fraction of these sequences contained splicing sites (SS). Analysis of transcription factors binding to putative intronic and exonic TFBS revealed that 5 and 16%, respectively, were NRs. The present study suggests crosstalk between steroid NRs, e.g., vitamin D, estrogen, progesterone, and retinoic acid endocrine systems, through cis-regulatory elements in conserved sequences of introns and exons. This investigation gives evidence for crosstalk between steroid hormones and contributes to novel targets for steroid NR regulation.
|
|
| 40. |
- Diaz Cruz, Maria Araceli, et al.
(författare)
-
Differential expression of protein disulfide-isomerase A3 isoforms, PDIA3 and PDIA3N, in human prostate cancer cell lines representing different stages of prostate cancer
- 2021
-
Ingår i: Molecular Biology Reports. - : Springer. - 0301-4851 .- 1573-4978. ; 48:3, s. 2429-2436
-
Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer (PCa) is a highly heterogeneous and unpredictable progressive disease. Sensitivity of PCa cells to androgens play a central role in tumor aggressiveness but biomarkers with high sensitivity and specificity that follow the progression of the disease has not yet been verified. The vitamin D endocrine system and its receptors, the Vitamin D Receptor (VDR) and the Protein Disulfide-Isomerase A3 (PDIA3), are related to anti-tumoral effects as well as carcinogenesis and have therefore been suggested as potential candidates for the prevention and therapy of several cancer forms, including PCa. In this study, we evaluated the mRNA expression of VDR and PDIA3 involved in vitamin D signaling in cell lines representing different stages of PCa (PNT2, P4E6, LNCaP, DU145 and PC3). This study further aimed to evaluate vitamin D receptors and their isoforms as potential markers for clinical diagnosis of PCa. A novel transcript isoform of PDIA3 (PDIA3N) was identified and found to be expressed in all PCa cell lines analyzed. Androgen-independent cell lines showed a higher mRNA expression ratio between PDIA3N/PDIA3 contrary to androgen-dependent cell lines that showed a lower mRNA expression ratio between PDIA3N/PDIA3. The structure of PDIA3N differed from PDIA3. PDIA3N was found to be a N-truncated isoform of PDIA3 and differences in protein structure suggests an altered protein function i.e. cell location, thioredoxin activity and affinity for 1,25(OH)2D3. Collectively, PDIA3 transcript isoforms, the ratio between PDIA3N/PDIA3 and especially PDIA3N, are proposed as candidate markers for future studies with different stages of PCa progression.
|
|
| 41. |
|
|
| 42. |
- Dong, Xuesi, et al.
(författare)
-
Trans-omics biomarker model improves prognostic prediction accuracy for early-stage lung adenocarcinoma
- 2019
-
Ingår i: Aging. - : Impact Journals, LLC. - 1945-4589. ; 11:16, s. 6312-6335
-
Tidskriftsartikel (refereegranskat)abstract
- Limited studies have focused on developing prognostic models with trans-omics biomarkers for early-stage lung adenocarcinoma (LUAD). We performed integrative analysis of clinical information, DNA methylation, and gene expression data using 825 early-stage LUAD patients from 5 cohorts. Ranger algorithm was used to screen prognosis-associated biomarkers, which were confirmed with a validation phase. Clinical and biomarker information was fused using an iCluster plus algorithm, which significantly distinguished patients into high- and low-mortality risk groups (Pdiscovery = 0.01 and Pvalidation = 2.71×10-3). Further, potential functional DNA methylation-gene expression-overall survival pathways were evaluated by causal mediation analysis. The effect of DNA methylation level on LUAD survival was significantly mediated through gene expression level. By adding DNA methylation and gene expression biomarkers to a model of only clinical data, the AUCs of the trans-omics model improved by 18.3% (to 87.2%) and 16.4% (to 85.3%) in discovery and validation phases, respectively. Further, concordance index of the nomogram was 0.81 and 0.77 in discovery and validation phases, respectively. Based on systematic review of published literatures, our model was superior to all existing models for early-stage LUAD. In summary, our trans-omics model may help physicians accurately identify patients with high mortality risk.
|
|
| 43. |
|
|
| 44. |
|
|
| 45. |
|
|
| 46. |
- Ekstrand, Eva-Maria, et al.
(författare)
-
High-rate anaerobic co-digestion of kraft mill fibre sludge and activated sludge by CSTRs with sludge recirculation
- 2016
-
Ingår i: Waste Management. - : Elsevier. - 0956-053X .- 1879-2456. ; 56, s. 166-172
-
Tidskriftsartikel (refereegranskat)abstract
- Kraft fibre sludge from the pulp and paper industry constitutes a new, widely available substrate for thebiogas production industry, with high methane potential. In this study, anaerobic digestion of kraft fibresludge was examined by applying continuously stirred tank reactors (CSTR) with sludge recirculation.Two lab-scale reactors (4L) were run for 800 days, one on fibre sludge (R1), and the other on fibre sludgeand activated sludge (R2). Additions of Mg, K and S stabilized reactor performance. Furthermore, theCa:Mg ratio was important, and a stable process was achieved at a ratio below 16:1. Foaming was abatedby short but frequent mixing. Co-digestion of fibre sludge and activated sludge resulted in more robustconditions, and high-rate operation at stable conditions was achieved at an organic loading rate of 4 gvolatile solids (VS) L1 day1, a hydraulic retention time of 4 days and a methane production of230 ± 10 Nm L per g VS.
|
|
| 47. |
- Ekstrand, Eva-Maria, 1985-, et al.
(författare)
-
Identifying targets for increased biogasproduction through chemical and organicmatter characterization of digestate from full‑scale biogas plants : what remains and why?
- 2022
-
Ingår i: Biotechnology for Biofuels and Bioproducts. - London, United Kingdom : BioMed Central. - 2731-3654. ; 15:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: This study examines the destiny of macromolecules in different full-scale biogas processes. From previousstudies it is clear that the residual organic matter in outgoing digestates can have significant biogas potential,but the factors dictating the size and composition of this residual fraction and how they correlate with the residualmethane potential (RMP) are not fully understood. The aim of this study was to generate additional knowledge of thecomposition of residual digestate fractions and to understand how they correlate with various operational and chemicalparameters. The organic composition of both the substrates and digestates from nine biogas plants operating onfood waste, sewage sludge, or agricultural waste was characterized and the residual organic fractions were linked tosubstrate type, trace metal content, ammonia concentration, operational parameters, RMP, and enzyme activity.Results: Carbohydrates represented the largest fraction of the total VS (32–68%) in most substrates. However, inthe digestates protein was instead the most abundant residual macromolecule in almost all plants (3–21 g/kg). Thedegradation efficiency of proteins generally lower (28–79%) compared to carbohydrates (67–94%) and fats (86–91%).High residual protein content was coupled to recalcitrant protein fractions and microbial biomass, either from thesubstrate or formed in the degradation process. Co-digesting sewage sludge with fat increased the protein degradationefficiency with 18%, possibly through a priming mechanism where addition of easily degradable substrates alsotriggers the degradation of more complex fractions. In this study, high residual methane production (> 140 L CH4/kgVS) was firstly coupled to operation at unstable process conditions caused mainly by ammonia inhibition (0.74 mgNH3-N/kg) and/or trace element deficiency and, secondly, to short hydraulic retention time (HRT) (55 days) relative tothe slow digestion of agricultural waste and manure.Conclusions: Operation at unstable conditions was one reason for the high residual macromolecule content andhigh RMP. The outgoing protein content was relatively high in all digesters and improving the degradation of proteinsrepresents one important way to increase the VS reduction and methane production in biogas plants. Post-treatment
|
|
| 48. |
- Ekstrand, Eva-Maria, 1985-, et al.
(författare)
-
The route towards stable and efficient anaerobic digestion of fibrous wastewater from pulp and paper mills in high-rate CSTRs with sludge recirculation
- 2015
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The pulp and paper industry carries high costs in wastewater treatment. By combining present techniques with anaerobic digestion (AD), expenses for electricity use and sludge disposal can be reduced. The large wastewater volumes require high-rate systems sensitive to suspended solids, and this has so far excluded treatment of the energy-rich wood fibres. In this study, AD of fibrous wastewater was examined in high-rate CSTRs with sludge recirculation. Two lab-scale reactors (4L) were run for 780 days. Once a day, reactor sludge was withdrawn and centrifuged. The main part of the supernatant was discarded, while the pellet was suspended with the substrate and returned to the reactor. This gave a sludge retention time of 10-16 days and a hydraulic retention time of 4-8 days. One reactor (denoted R1) was fed with fibre sludge, and the second reactor (denoted R2) was co-digesting fibre sludge and activated sludge. Both substrates were taken from a Kraft mill in Sweden. Initially, both reactors experienced frequent drops in pH, and continuous alkali supplements were necessary for process stability. Additions of magnesium and potassium were also needed to obtain stable process performance at an OLR of 3 g VS L-1·day-1. R1 and R2 behaved similarly, but R2 (co-digestion) was more robust with less or no fluctuations in VFA and pH. Addition of activated sludge also to R1 allowed an increase in OLR to 4 g VS L-1·day-1. In summary, stable and efficient operation of a high-rate CSTR with sludge recirculation digesting fibre sludge was achieved at an OLR of 4 g VS L-1·day-1, a HRT of 4 days and a methane production of 260±20 Nml. In addition, co-digestion with activated sludge stabilized the performance at increased OLR and thus gave more methane produced per reactor volume.
|
|
| 49. |
|
|
| 50. |
- Estrada, Karol, et al.
(författare)
-
Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
-
Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
|
|
