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1.
  • Landberg, Eva, et al. (författare)
  • Disialo–trisialo bridging of transferrin is due to increased branching and fucosylation of the carbohydrate moiety
  • 2012
  • Ingår i: Clinica Chimica Acta. - : Elsevier. - 0009-8981 .- 1873-3492. ; 414, s. 58-64
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundCarbohydrate deficient transferrin (CDT) is used for detection of alcohol abuse and follow-up. High performance liquid chromatography (HPLC) of transferrin glycoforms is highly specific for identification of alcohol abuse, but unresolved disialo- and trisialotransferrin glycoforms sometimes makes interpretation difficult. The cause of this phenomenon is unknown, cannot be explained by genetic variants of transferrin, but seems to be associated with liver disease.MethodsNineteen serum samples showing di–tri bridging when analyzed by HPLC were collected. Transferrin was purified by affinity chromatography, and N-linked oligosaccharides were released enzymatically. The N-glycans were further analyzed by high performance anion-exchange chromatography with pulsed amperometric detection and MALDI-TOF mass spectrometry.ResultsThe HPLC-analysis showed three different types of glycoform patterns. The N-glycans from fifteen samples showed patterns with increased number of triantennary structures containing one or two fucose residues. One sample contained an increased amount of triantennary glycans without fucose. Three samples showed a glycosylation pattern similar to normal transferrin.ConclusionsThe di–tri bridging phenomenon was associated with alterations in transferrin glycosylation in the majority of cases. Transferrin contained a higher extent of triantennary and often fucosylated N-linked oligosaccharides. These results may be important in future diagnostic approaches to liver diseases.
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2.
  • Spreckels, Johanne, et al. (författare)
  • Lactobacillus reuteri Colonisation of Extremely Preterm Infants in a Randomised Placebo-Controlled Trial
  • 2021
  • Ingår i: Microorganisms. - : MDPI AG. - 2076-2607. ; 9:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Lactobacillus reuteri DSM 17938 supplementation reduces morbidities in very low birth weight infants (<1500 g), while the effect on extremely low birth weight infants (ELBW, <1000 g) is still questioned. In a randomised placebo-controlled trial (ClinicalTrials.gov ID NCT01603368), head growth, but not feeding tolerance or morbidities, improved in L. reuteri-supplemented preterm ELBW infants. Here, we investigate colonisation with the probiotic strain in preterm ELBW infants who received L. reuteri DSM 17938 or a placebo from birth to postmenstrual week (PMW) 36. Quantitative PCR was used on 582 faecal DNA samples collected from 132 ELBW infants at one, two, three, and four weeks, at PMW 36, and at two years of age. Human milk oligosaccharides were measured in 31 milk samples at two weeks postpartum. At least 86% of the ELBW infants in the L. reuteri group were colonised with the probiotic strain during the neonatal period, despite low gestational age, high antibiotic pressure, and independent of infant feeding mode. Higher concentrations of lacto-N-tetraose, sialyl-lacto-N-neotetraose c, and 6 '-sialyllactose in mother's milk weakly correlated with lower L. reuteri abundance. Within the L. reuteri group, higher L. reuteri abundance weakly correlated with a shorter time to reach full enteral feeding. Female sex and L. reuteri colonisation improved head growth from birth to four weeks of age. In conclusion, L. reuteri DSM 17938 supplementation leads to successful colonisation in ELBW infants.
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3.
  • Akrap, Nina, et al. (författare)
  • Identification of Distinct Breast Cancer Stem Cell Populations Based on Single-Cell Analyses of Functionally Enriched Stem and Progenitor Pools
  • 2016
  • Ingår i: Stem Cell Reports. - : Elsevier BV. - 2213-6711. ; 6:1, s. 121-136
  • Tidskriftsartikel (refereegranskat)abstract
    • The identification of breast cancer cell subpopulations featuring truly malignant stem cell qualities is a challenge due to the complexity of the disease and lack of general markers. By combining extensive single-cell gene expression profiling with three functional strategies for cancer stem cell enrichment including anchorage-independent culture, hypoxia, and analyses of low-proliferative, label-retaining cells derived from mammospheres, we identified distinct stem cell clusters in breast cancer. Estrogen receptor (ER)alpha+ tumors featured a clear hierarchical organization with switch-like and gradual transitions between different clusters, illustrating how breast cancer cells transfer between discrete differentiation states in a sequential manner. ER alpha- breast cancer showed less prominent clustering but shared a quiescent cancer stem cell pool with ER alpha+ cancer. The cellular organization model was supported by single-cell data from primary tumors. The findings allow us to understand the organization of breast cancers at the single-cell level, thereby permitting better identification and targeting of cancer stem cells.
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4.
  • Almasri, Fidele, et al. (författare)
  • Dietary Intake of Fructooligosaccharides Protects against Metabolic Derangements Evoked by Chronic Exposure to Fructose or Galactose in Rats
  • 2024
  • Ingår i: Molecular Nutrition and Food Research. - 1613-4125 .- 1613-4133. ; 68:4
  • Tidskriftsartikel (refereegranskat)abstract
    • ScopeDiets rich in fat and sugars evoke chronic low-grade inflammation, leading to metabolic derangements. This study investigates the impact of fructose and galactose, two commonly consumed simple sugars, on exacerbation of the harmful effects caused by high fat intake. Additionally, the potential efficacy of fructooligosaccharides (FOS), a fermentable dietary fiber, in counteracting these effects is examined.Methods and resultsMale Sprague-Dawley rats (six/group) are fed 8 weeks as follows: control 5% fat diet (CNT), 20% fat diet (FAT), FAT+10% FOS diet (FAT+FOS), FAT+25% galactose diet (FAT+GAL), FAT+GAL+10% FOS diet (FAT+GAL+FOS), FAT+25% fructose diet (FAT+FRU), FAT+FRU+10% FOS diet (FAT+FRU+FOS). The dietary manipulations tested do not affect body weight gain, blood glucose, or markers of systemic inflammation whereas significant increases in plasma concentrations of triacylglycerols, cholesterol, aspartate aminotransferase, and alanine aminotrasferase are detected in both FAT+FRU and FAT+GAL compared to CNT. In the liver and skeletal muscle, both sugars induce significant accumulation of lipids and advanced glycation end-products (AGEs). FOS supplementation prevents these impairments.ConclusionThis study extends the understanding of the deleterious effects of a chronic intake of simple sugars and demonstrates the beneficial role of the prebiotic FOS in dampening the sugar-induced metabolic impairments by prevention of lipid and AGEs accumulation. This rat trial shows the detrimental effects of two commonly consumed simple sugars, fructose and galactose, when added to a fat-enriched diet, as is common in modern Western nutrition. Protective effects of fermentable dietary fiber (FOS) supplementation due to reduced accumulation of AGEs, that are harmful compounds formed when protein or fat combine with sugar, are observed.image
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5.
  • Andersson, Per, et al. (författare)
  • Consequences of high-sensitivity troponin T testing applied in a primary care population with chest pain compared with a commercially available point-of-care troponin T analysis : an observational prospective study
  • 2015
  • Ingår i: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 8:1, s. 1-9
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:There is a demand for a highly sensitive and specific point-of care test to detect acute myocardial infarction (AMI). It is unclear if a high-sensitivity troponin assay will have enough discriminative power to become a decision support in primary care. The aim of this study was to evaluate a high-sensitivity troponin T assay performed in three primary health care centres in southeast Sweden and to compare the outcome with a point-of-care troponin T test.METHODS:This study included 115 patients who consulted their general practitioner for chest pain, dyspnoea on exertion, unexplained weakness and/or fatigue in the last 7days. Troponin T was analysed by a point-of-care test and a high-sensitivity method together with N-terminal pro-B-type natriuretic peptide (NT-proBNP) and creatinine. All patients were checked for AMI or unstable angina (UA) within 30days of study enrolment. Univariate and multivariate logistic regression was carried out to examine possible connections between troponin T[greater than or equal to]15ng/L, clinical variables and laboratory findings at baseline. In addition, 21 patients with troponin T[greater than or equal to]15ng/L and no signs of AMI or UA were followed up for 2-3years.RESULTS:Three patients were diagnosed with AMI and three with UA. At the [greater than or equal to]15ng/L cut-off, the troponin T method had 100% sensitivity, 75% specificity for AMI and a positive predictive value of 10%. The troponin T point-of-care test missed one case of AMI and the detection limit was 50ng/L. Troponin T[greater than or equal to]15ng/L was correlated to age [greater than or equal to]65years (odds ratio (OR), 10.9 95% CI 2.28-51.8) and NT-proBNP in accordance with heart failure (OR 8.62 95% CI 1.61-46.1). Fourteen of the 21 patients, without signs of AMI or UA at baseline, still had increased troponin T at follow-up after 2-3years.CONCLUSIONS:A high-sensitivity troponin T assay could become useful in primary care as a point-of-care test for patients <65years. For patients older than 65-70years, a higher decision limit than [greater than or equal to]15ng/L should be considered and used in conjunction with clinical parameters and possibly with NT-proBNP.
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6.
  • Atanasova, Diana, 1991-, et al. (författare)
  • Glycoproteomic profile of human tissue-nonspecific alkaline phosphatase expressed in osteoblasts
  • 2024
  • Ingår i: JBMR Plus. - : Oxford University Press. - 2473-4039. ; 8:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Tissue-nonspecific alkaline phosphatase (TNALP) is a glycoprotein expressed by osteoblasts that promotes bone mineralization. TNALP catalyzes the hydrolysis of the mineralization inhibitor inorganic pyrophosphate and ATP to provide inorganic phosphate, thus controlling the inorganic pyrophosphate/inorganic phosphate ratio to enable the growth of hydroxyapatite crystals. N-linked glycosylation of TNALP is essential for protein stability and enzymatic activity and is responsible for the presence of different bone isoforms of TNALP associated with functional and clinical differences. The site-specific glycosylation profiles of TNALP are, however, elusive. TNALP has 5 potential N-glycosylation sites located at the asparagine (N) residues 140, 230, 271, 303, and 430. The objective of this study was to reveal the presence and structure of site-specific glycosylation in TNALP expressed in osteoblasts. Calvarial osteoblasts derived from Alpl+/− expressing SV40 Large T antigen were transfected with soluble epitope-tagged human TNALP. Purified TNALP was analyzed with a lectin microarray, matrix-assisted laser desorption/ionization-time of flight mass spectrometry, and liquid chromatography with tandem mass spectrometry. The results showed that all sites (n = 5) were fully occupied predominantly with complex-type N-glycans. High abundance of galactosylated biantennary N-glycans with various degrees of sialylation was observed on all sites, as well as glycans with no terminal galactose and sialic acid. Furthermore, all sites had core fucosylation except site N271. Modelling of TNALP, with the protein structure prediction software ColabFold, showed possible steric hindrance by the adjacent side chain of W270, which could explain the absence of core fucosylation at N271. These novel findings provide evidence for N-linked glycosylation on all 5 sites of TNALP, as well as core fucosylation on 4 out of 5 sites. We anticipate that this new knowledge can aid in the development of functional and clinical assays specific for the TNALP bone isoforms.
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7.
  • Axelsson Landberg, Tove, et al. (författare)
  • Hälsoprojekt ökar barns lust att röra på sig
  • 2005
  • Ingår i: Svensk Idrottsforskning. ; 4, s. 1-6
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Många skolor driver glädjande nog hälsoprojekt idag, bland annat som följd av Handslaget. Få har dock utvärderats ännu. Påverkas barnens attityder och vanor? Ett nyligen avslutat hälsoprojekt i Partille kommun tyder på detta. Det Bunkeflo-inspirerande hälsoprojektet löpte under en tvåårsperiod, ht 2002 till vt 2004, och innefattade utökad fysisk aktivitet i olika former samt massage och avslappning för de minsta barnen. Projektet följdes upp med enkäter till barnen före och efter projektet samt en fokusgruppintervju med nyckelpersonal. Resultatet har redovisats i form av en C-uppsats vid Göteborgs universitet, vilket sammanfattas i nedanstående artikel.
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8.
  • Busch, Susann, et al. (författare)
  • Cellular organization and molecular differentiation model of breast cancer-associated fibroblasts
  • 2017
  • Ingår i: Molecular Cancer. - : Springer Science and Business Media LLC. - 1476-4598. ; 16:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The role of cancer-associated fibroblasts (CAFs) during tumour progression is obscured by the inherently complex, heterotypic nature of fibroblast cells and behaviours in various subtypes of malignancies. Therefore, we sought to identify distinct fibroblast subpopulations at the single-cell level. Methods: Using single-cell quantitative PCR as a powerful tool to study heterogeneity and rare cell events, in a high-throughput manner a panel of gene targets are run simultaneously on transcripts isolated from single cells obtained by fluorescence-activated cell sort. Assessment of cells with stem-like characteristics was attained by anchorage-independent, anoikis-resistant culture. Results: Single-cell analysis of fibroblasts and their tumour-activated counterparts demonstrated molecularly distinct cell types defined by differential expression of characteristic mesenchymal and fibroblast activation markers. Identified subpopulations presented overlapping gene expression patterns indicating transitional molecular states during fibroblast differentiation. Using single-cell resolution data we generated a molecular differentiation model which enabled the classification of patient-derived fibroblasts, validating our modelling approach. Remarkably, a subset of fibroblasts displayed expression of pluripotency markers, which was enriched for in non-adherent conditions. Yet the ability to form single-cell derived spheres was generally reduced in CAFs and upon fibroblast activation through TGF beta 1 ligand and cancer cell-secreted factors. Hence, our data imply the existence of putative stem/progenitor cells as a physiological feature of undifferentiated fibroblasts. Conclusions: Within this comprehensive study we have identified distinct and intersecting molecular profiles defining fibroblast activation states and propose that underlying cellular heterogeneity, fibroblasts are hierarchically organized. Understanding the molecular make-up of cellular organization and differentiation routes will facilitate the discovery of more specific markers for stromal subtypes and targets for anti-stromal therapies.
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9.
  • Eklund, D. Magnus, et al. (författare)
  • Homologues of the Arabidopsis thaliana SHI/STY/LRP1 genes control auxin biosynthesis and affect growth and development in the moss Physcomitrella patens
  • 2010
  • Ingår i: Development. - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 137:8, s. 1275-1284
  • Tidskriftsartikel (refereegranskat)abstract
    • The plant hormone auxin plays fundamental roles in vascular plants. Although exogenous auxin also stimulates developmental transitions and growth in non-vascular plants, the effects of manipulating endogenous auxin levels have thus far not been reported. Here, we have altered the levels and sites of auxin production and accumulation in the moss Physcomitrella patens by changing the expression level of homologues of the Arabidopsis SHI/STY family proteins, which are positive regulators of auxin biosynthesis genes. Constitutive expression of PpSHI1 resulted in elevated auxin levels, increased and ectopic expression of the auxin response reporter GmGH3pro:GUS, and in an increased caulonema/chloronema ratio, an effect also induced by exogenous auxin application. In addition, we observed premature ageing and necrosis in cells ectopically expressing PpSHI1. Knockout of either of the two PpSHI genes resulted in reduced auxin levels and auxin biosynthesis rates in leafy shoots, reduced internode elongation, delayed ageing, a decreased caulonema/chloronema ratio and an increased number of axillary hairs, which constitute potential auxin biosynthesis sites. Some of the identified auxin functions appear to be analogous in vascular and non-vascular plants. Furthermore, the spatiotemporal expression of the PpSHI genes and GmGH3pro:GUS strongly overlap, suggesting that local auxin biosynthesis is important for the regulation of auxin peak formation in non-vascular plants.
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10.
  • Ekman, Bertil, et al. (författare)
  • Urine oligosaccharide pattern in patients with hyperprolactinaemia
  • 2015
  • Ingår i: Glycoconjugate Journal. - : Springer. - 0282-0080 .- 1573-4986. ; 32:8, s. 635-641
  • Tidskriftsartikel (refereegranskat)abstract
    • Free milk-type oligosaccharides are produced during pregnancy and lactation and may have an impact on several cells in the immune system. Our aim was to investigate if patients with isolated hyperprolactinaemia, not related to pregnancy, also have increased synthesis and urinary excretion of milk-type oligosaccharides and to compare the excretion pattern with that found during pregnancy. Urine samples were collected as morning sample from 18 patients with hyperprolactinaemia, 13 healthy controls with normal prolactin levels and four pregnant women. After purification, lactose and free oligosaccharides were analysed and quantified by high-performance anion-exchange chromatography with pulsed amperometric detection. The identity of peaks was confirmed by exoglycosidase treatment and comparison with oligosaccharide standards. Prolactin was measured in serum collected between 09 and 11 a.m. by a standardized immunochemical method. Patients with hyperprolactinaemia had higher urinary excretion of lactose than normoprolactinemic controls and urinary lactose correlated positively to prolactin levels (r = 0.51, p < 0.05). Increased levels of the fucosylated oligosaccharides 2-fucosyl lactose and lacto-di-fucotetraose were found in urine from three and two patients, respectively. The acidic oligosaccharide 3-sialyl lactose was found in high amount in urine from two patients with prolactin of >10,000 mU/l. However, pregnant women in their third trimester had the highest concentration of all these oligosaccharides and excretion increased during pregnancy. This study is first to show that both lactose and certain fucosylated and sialylated milk-type oligosaccharides are increased in some patients with hyperprolactinaemia. It remains to elucidate the functional importance of these findings.
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11.
  • Ernersson, Åsa, et al. (författare)
  • Reduced Health Related Quality of Life, Increased Fatigue and Daytime Sleepiness in Women with Hyperprolactinemia
  • 2023
  • Ingår i: Hormone and Metabolic Research. - : Thieme Medical Publishers. - 0018-5043 .- 1439-4286. ; 55:4, s. 266-272
  • Tidskriftsartikel (refereegranskat)abstract
    • Prolactin has many physiological effects and seems to be involved in the human quality of life and well-being. The aim of this study was to describe health related quality of life, fatigue and daytime sleepiness in women with untreated hyperprolactinemia. In total 32 women (mean age 37.0 ± 10.9) with verified hyperprolactinemia completed a questionnaire including questions on fatigue, measured with the Swedish version of the Fatigue Impact Scale (FIS), propensity to fall in sleep, measured with the Swedish version of the Epworth Sleepiness Scale (ESS), and Health related quality of life (HRQoL), measured by the Short-Form-36 scale (SF-36). For comparison Swedish normative data were used. The women were also interviewed regarding different symptoms related to hyperprolactinemia and the answers were analyzed using qualitative content analysis. HRQoL, as measured with SF-36, was significantly lower in all dimensions, except in physical function, compared to the Swedish reference population. Total FIS was 54.3 (41.1) and mean score on the ESS was 8.7 (4.2) indicating increased fatigue and deterioration in night sleep. The women felt very tired, and several of them rarely felt rested in the morning. The restless night sleep and the fatigue during the daytime got them to feel feeble and sometimes to find it difficult to concentrate, which affected both their mood and life in general. Women diagnosed with hyperprolactinemia reported deterioration in night sleep, increased rate of fatigue, and a reduced health related quality of life in comparison with the reference population.
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12.
  • Ewerman, Lea, et al. (författare)
  • Immunomodulating Effects Depend on Prolactin Levels in Patients with Hyperprolactinemia
  • 2020
  • Ingår i: Hormone and Metabolic Research. - Stuttgart : Thieme Medical Publishers. - 0018-5043 .- 1439-4286. ; 52:04, s. 228-235
  • Tidskriftsartikel (refereegranskat)abstract
    • Prolactin is known to have immune modulatory effects acting through the prolactin receptor, which is present on a variety of immune cells. Certain chemokines contribute to form the type of T helper (Th) preponderance in the immune response. The objective of this work was to assess if hyperprolactinemia not related to pregnancy is associated with changes in circulating levels of chemokines and other immunological markers. In this cross sectional study, 35 patients with hyperprolactinemia (5 men), and 102 healthy blood donors (19 men) were included. Serum levels of Th1- Th2- and Th17-associated chemokines, C-reactive protein, immunoglobulins, and the B cell attracting chemokine CXCL13 were assessed. The hyperprolactinemic group had significantly higher levels of Th2 associated CCL22 (p=0.022), Th17 associated CXCL1 (p=0.001), B cell attracting CXCL13 (p=0.003), and C-reactive protein (p<0.001) compared to controls, and these proteins were also positively correlated with prolactin levels. While differences in CCL22, CXCL1, CXCL13, and C-reactive protein were present in patients with low or moderate hyperprolactinemia, no differences were observed at high (>3600 mU/l) prolactin levels. To evaluate a possible dose-associated response to prolactin, an in vitro model was used, showing prolactin-induced increase in T-helper cell activation at moderate levels, while activation decreased at higher levels. Hyperprolactinemia seems to have several immunomodulatory effects and was associated with increased levels of chemokines associated with Th2 and Th17 responses and B cell attraction. However, patients with greatly increased prolactin had normal levels of chemokines, and in vitro, high levels of prolactin decreased T-helper cell activation.
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13.
  • Gawria, Ghassaan, et al. (författare)
  • A comparison of stability of chemical analytes in plasma from the BD Vacutainer (R) Barricor (TM) tube with mechanical separator versus tubes containing gel separator
  • 2020
  • Ingår i: Journal of clinical laboratory analysis (Print). - : WILEY. - 0887-8013 .- 1098-2825. ; 34:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There is a need of prolonged stability of certain chemical analytes in lithium heparin tubes with separators. A new tube with a mechanical separator has recently been launched (Barricor (TM)), which according to the manufacturer may have these benefits. The aim of this study was to evaluate stability performance of this tube in comparison with plasma gel tubes under clinically realistic circumstances. Methods: Blood was collected in tubes containing lithium heparin with different separators; gel separator (Vacutainer (R) PST (TM), Becton Dickinson and Vacuette (R), Greiner bio-one) and mechanical separator (Vacutainer (R) Barricor (TM), Becton Dickinson). All tubes had an aspiration volume of 3 mL and were centrifuged at similar time and force. Tubes were transported manually or by car. Seven analytes from 122 patients were analyzed after 3 to 80 hours by Cobas c701 (Roche). Results The Barricor (TM) tube showed increased stability of phosphate and potassium and similar stability of aspartate aminotransferase, glucose, homocysteine, lactate dehydrogenase, and magnesium compared with gel tubes. Maximal allowable bias for phosphate was exceeded after 68 hours for Barricor (TM) tubes compared with 29 or 35 hours for gel tubes and for potassium after 40 hours for Barricor (TM) tubes vs 9 or 12 hours for gel tubes. Transportation did not affect stability. Hemolysis index was slightly lower in Barricor tubes than in gel tubes (P = .01). Conclusion Implementing the new Barricor (TM) tube will improve stability of potassium and phosphate in plasma. Blood sampling facilities far from the laboratory may benefit from using these tubes, thus diminishing preanalytical errors.
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14.
  • Gunter, Marc J, et al. (författare)
  • Coffee drinking and mortality in 10 European countries : A multinational cohort study
  • 2017
  • Ingår i: Annals of Internal Medicine. - 0003-4819 .- 1539-3704. ; 167:4, s. 236-247
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The relationship between coffee consumption and mortality in diverse European populations with variable coffee preparation methods is unclear. Objective: To examine whether coffee consumption is associated with all-cause and cause-specific mortality. Design: Prospective cohort study. Setting: 10 European countries. Participants: 521 330 persons enrolled in EPIC (European Prospective Investigation into Cancer and Nutrition). Measurements: Hazard ratios (HRs) and 95% CIs estimated using multivariable Cox proportional hazards models. The association of coffee consumption with serum biomarkers of liver function, inflammation, and metabolic health was evaluated in the EPIC Biomarkers subcohort (n = 14 800). Results: During a mean follow-up of 16.4 years, 41 693 deaths occurred. Compared with nonconsumers, participants in the highest quartile of coffee consumption had statistically significantly lower all-cause mortality (men: HR, 0.88 [95% CI, 0.82 to 0.95]; P for trend < 0.001; women: HR, 0.93 [CI, 0.87 to 0.98]; P for trend = 0.009). Inverse associations were also observed for digestive disease mortality for men (HR, 0.41 [CI, 0.32 to 0.54]; P for trend < 0.001) and women (HR, 0.60 [CI, 0.46 to 0.78]; P for trend < 0.001). Among women, there was a statistically significant inverse association of coffee drinking with circulatory disease mortality (HR, 0.78 [CI, 0.68 to 0.90]; P for trend < 0.001) and cerebrovascular disease mortality (HR, 0.70 [CI, 0.55 to 0.90]; P for trend = 0.002) and a positive association with ovarian cancer mortality (HR, 1.31 [CI, 1.07 to 1.61]; P for trend = 0.015). In the EPIC Biomarkers subcohort, higher coffee consumption was associated with lower serum alkaline phosphatase; alanine aminotransferase; aspartate aminotransferase; 7-glutamyltransferase; and, in women, C-reactive protein, lipoprotein(a), and glycated hemoglobin levels. Limitations: Reverse causality may have biased the findings; however, results did not differ after exclusion of participants who died within 8 years of baseline. Coffee-drinking habits were assessed only once. Conclusion: Coffee drinking was associated with reduced risk for death from various causes. This relationship did not vary by country.
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15.
  • Hirschberg, Daniel, et al. (författare)
  • Altered immunoglobulin G glycosylation in patients with isolated hyperprolactinaemia
  • 2021
  • Ingår i: PLOS ONE. - San Francisco, USA : Public Library of Science. - 1932-6203. ; 16:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Prolactin is a peptide hormone produced in the anterior pituitary, which increase in several physiological and pathological situations. It is unclear if hyperprolactinaemia may affect glycosylation of immunoglobulin G (IgG). Twenty-five patients with hyperprolactinemia and 22 healthy control subjects were included in the study. The groups had similar age and gender distribution. A panel of hormonal and haematological analyses, creatinine, glucose, liver enzymes and immunoglobulins were measured by routine clinical methods. IgG was purified from serum by Protein G Sepharose. Sialic acid was released from IgG by use of neuraminidase followed by quantification on high performance anion-exchange chromatography with pulsed amperometric detection. Tryptic glycopeptides of IgG was analysed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Hormone and immunoglobulin levels were similar in the two groups, except for IgA and prolactin. Significantly higher IgG1 and IgG2/3 galactosylation was found in the patient group with hyperprolactinaemia compared to controls. (A significant correlation between prolactin and IgG2/3 galactosylation (Rs 0.61, p<0.001) was found for samples with prolactin values below 2000 mIU/L. The relative amount of sialylated and bisecting glycans on IgG did not differ between patients and controls. The four macroprolactinaemic patients showed decreased relative amount of bisecting IgG2/3 glycans. Hyperprolactinaemia was found to be associated with increased galactosylation of IgG1 and IgG2/3. This may have impact on IgG interactions with Fc-receptors, complement and lectins, and consequently lead to an altered immune response.
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16.
  • Hueso Estornell, Leandro, et al. (författare)
  • SHI/STY Genes Affect Pre- and Post-meiotic Anther Processes in Auxin Sensing Domains in Arabidopsis
  • 2018
  • Ingår i: Frontiers in Plant Science. - : Frontiers Media SA. - 1664-462X. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • In flowering plants, mature sperm cells are enclosed in pollen grains formed in structures called anthers. Several cell layers surrounding the central sporogenous cells of the anther are essential for directing the developmental processes that lead to meiosis, pollen formation, and the subsequent pollen release. The specification and function of these tissues are regulated by a large number of genetic factors. Additionally, the plant hormone auxin has previously been shown to play important roles in the later phases of anther development. Using the R2D2 auxin sensor system we here show that auxin is sensed also in the early phases of anther cell layer development, suggesting that spatiotemporal regulation of auxin levels is important for early anther morphogenesis. Members of the SHI/STY transcription factor family acting as direct regulators of YUC auxin biosynthesis genes have previously been demonstrated to affect early anther patterning. Using reporter constructs we show that SHI/STY genes are dynamically active throughout anther development and their expression overlaps with those of three additional downstream targets, PAO5,EOD3 and PGL1. Characterization of anthers carrying mutations in five SHI/STY genes clearly suggests that SHI/STY transcription factors affect anther organ identity. In addition, their activity is important to repress periclinal cell divisions as well as premature entrance into programmed cell death and cell wall lignification, which directly influences the timing of anther dehiscence and the pollen viability. The SHI/STY proteins also prevent premature pollen germination suggesting that they may play a role in the induction or maintenance of pollen dormancy.
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17.
  • Isaksson, Hanna, et al. (författare)
  • High-fiber rye diet increases ileal excretion of energy and macronutrients compared with low-fiber wheat diet independent of meal frequency in ileostomy subjects
  • 2013
  • Ingår i: Food & Nutrition Research. - Järfälla : Co-Action Publishing. - 1654-6628 .- 1654-661X. ; 57, s. 18519-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Whole-grain foods and cereal dietary fiber intake is associated with lower body weight. This may partly result from lower energy utilization of high-fiber diets. Objective: In the present study, the impact on ileal excretion of energy and macronutrients in response to a rye bread high-fiber diet compared to a refined wheat low-fiber diet was investigated. Furthermore, the effect of meal frequency on apparent absorption of nutrients was studied for the first time. Design: Ten participants that had undergone ileostomy consumed standardized iso-caloric diets, including low-fiber wheat bread (20 g dietary fiber per day) for 2 weeks followed by high-fiber rye bread (52 g dietary fiber per day) for 2 weeks. The diets were consumed in an ordinary (three meals per day) and a nibbling (seven meals per day) meal frequency in a cross-over design. Ileal effluents were collected during 24 h at the third day of each of the four dietary periods and analyzed for gross energy and nutrient contents. Results: The results showed that intake of rye bread high-fiber diet compared to the refined wheat low-fiber diet caused an increase in ileal excretion of energy and macronutrients. The effect was independent of meal frequency. This suggests that a high intake of rye may result in lower availability of macronutrients for small intestinal digestion and absorption. A regular intake of rye may therefore have implications for weight management.
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18.
  • Landberg, Eva, 1966-, et al. (författare)
  • Changes in Glycosylation of Human Bile-Salt-Stimulated Lipase during Lactation
  • 2000
  • Ingår i: Archives of Biochemistry and Biophysics. - : Elsevier BV. - 0003-9861 .- 1096-0384. ; 377:2, s. 246-254
  • Tidskriftsartikel (refereegranskat)abstract
    • Bile-salt-stimulated lipase (BSSL) is an enzyme in human milk, which is important for the fat digestion in the newborn infant. BSSL is highly glycosylated and includes one site for N-glycosylation and several sites for O-glycosylation. BSSL has previously been found to express Lewis a, Lewis b, and Lewis x carbohydrate antigens. In this study, glycosylation of BSSL was studied at different times during lactation. BSSL was purified from milk collected individually from four donors at several different times during the first 6 months of lactation. The BSSL glycans were characterized through monosaccharide analysis, high-pH anion-exchange chromatography, matrix-assisted laser desorption–ionization mass spectrometry, and ELISA. Both total carbohydrate content and relative amount of sialic acid were higher in BSSL from the first lactation month as compared to BSSL from milk collected later in lactation. BSSL from the first lactation month also showed a different composition of sialylated O-linked glycans and the N-linked oligosaccharides consisted of lower amounts of fucosylated structures compared to later in lactation. We also found a gradual increase in the expression of the carbohydrate epitope Lewis x on BSSL throughout the lactation period. This study shows that glycosylation of BSSL is dependent on blood group phenotype of the donor and changes substantially during the lactation period.
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19.
  • Landberg, Eva, et al. (författare)
  • Changes in the relative amounts of α2-3 and α2-6 linked sialic acid on free and protein-bound milk oligosaccharides during lactation
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Human milk contains large amounts of oligosaccharides, both in free and protein-bound forms. Sialic acid is a common constituent of milk oligosaccharides and is present α2-3 or α2-6 linked to galactose, α2-6 to N-acetyl glucosamine or α2-6 to N-acetyl galactosamine. High-performance anionexchange chromatography with pulsed amperometric detection (HPAEC-PAD) was used to quantify four major sialylated milk oligosaccharides. The concentrations of the individual oligosaccharides were analyzed in milk from five donors, followed separately during six to nine months of lactation. The oligosaccharides containing sialic acid a2-6 linked to galactose ( 6-sialyl lactose and LSTc) decreased more than tenfold during lactation. In contrast, the concentration of 3-sialyl lactose (3-SL) containing sialic acid a2-3 linked to galactose remained constant during nine months of lactation. Disialyl lacto-Ntetraose (DSLNT) which contain sialic acid linked α2-3 to Gal and α2-6 to GlcNAc decreased approximately threefold during lactation. Lectin ELISA was used to analyze sialic acid on the secreted milk glycoprotein bile-salt-stimulated lipase (BSSL ). There was a gradual decrease in the binding of Sambucus Nigra lectin to BSSL, indicating decreased amount of α2-6 linked sialic acid during lactation. In contrast, binding of Maackia Amurensis lectin remained constant, indicating a constant expression of α2-3 linked sialic acid on BSSL during lactation. This suggests a shift from preferentially 6-linked to 3-linked sialic acid on free and protein-bound oligosaccharides during lactation. The shift may reflect changes in sialyltransferase activities and, on a higher level, changes in the population of mammary epithelial cells. This finding may be of importance for the development of a correct immune response to environmental challenges.
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20.
  • Landberg, Eva, 1966-, et al. (författare)
  • Detection of molecular variants of prolactin in human serum, evaluation of a method based on ultrafiltration
  • 2007
  • Ingår i: Clinica Chimica Acta. - : Elsevier BV. - 0009-8981 .- 1873-3492. ; 376:1-2, s. 220-225
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundIn human blood, there are several molecular variants of prolactin with different biological effects. There is a need for new methods to detect and quantify these variants in order to fully understand the pathophysiological role of prolactin.MethodsA method based on ultrafiltration was optimized, validated and compared to PEG precipitation. Serum samples from 84 patients were analyzed before and after pre treatment on two immunoassays, Elecsys (Roche) and Access (Beckman). Protein G precipitation was used to confirm presence of macroprolactin.ResultsThe recovery of prolactin after ultrafiltration was lower than after PEG precipitation. A limit of 40% recovery after PEG precipitation corresponded to 27% recovery after ultrafiltration. Using these limits there were total agreement regarding detection of macroprolactin (rs = 0.96). In contrast, recovery of prolactin in samples without macroprolactin showed a considerable disagreement between ultrafiltration and PEG precipitation (rs = 0.48). Within-run CV was 4% for the ultrafiltration method. The correlation coefficient (r) between the immunoassays was 0.96 after ultrafiltration.ConclusionsUltrafiltration can be used to compare different prolactin immunoassays and to detect macroprolactin in assays with interference from PEG. For samples without macroprolactin ultrafiltration may give additional information reflecting individual variations of other molecular variants of prolactin.
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21.
  • Landberg, Eva, et al. (författare)
  • Evaluation of venous plasma glucose measured by point-of-care testing (Accu-Chek Inform II) and a hospital laboratory hexokinase method (Cobas c701) in oral glucose tolerance testing during pregnancy - a challenge in diagnostic accuracy
  • 2021
  • Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 81:8, s. 607-614
  • Tidskriftsartikel (refereegranskat)abstract
    • To diagnose gestational diabetes mellitus (GDM), plasma glucose measurements during oral glucose tolerance test (OGTT) put high demands on the methods in terms of accuracy. The aim was to evaluate and compare diagnostic performance of a point-of-care test and a glucose hexokinase laboratory method. Using risk-based screening, 175 pregnant women were included. They underwent a 75 g OGTT in their 28th (median) week of gestation. Venous blood was collected in two different tubes. Plasma glucose was measured on Cobas c701 and in duplicates on AccuChek Inform II (both methods from Roche Diagnostics). Accuracy was assessed by participating in external control programs with reference method assigned values. The methods were compared for all samples (n = 512) by regression analysis; slope of 0.90 (95% CI: 0.89-0.92), intercept of 0.12 (95% CI: 0.011-0.22) and r(s) of 0.968. The average bias between AccuChek Inform II and Cobas c701 was -8%. The proportion of women diagnosed with GDM was 25% based on AccuChek Inform II versus 55% for Cobas c701. Results from the external control program showed a bias of approximately 5% for Cobas c701 and no significant bias for AccuChek Inform II. Cobas c701 showed a large bias both towards Accu-Chek Inform II and the reference method used in the external control program, clearly exceeding the desirable bias of <2.6%. The lack of accuracy has great implications on either over- or under-diagnosis of GDM.
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22.
  • Landberg, Eva, 1966- (författare)
  • Free oligosaccharides and glycosylation of bile salt-stimulated lipase in human milk
  • 2001
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Bile salt-stimulated lipase (BSSL) is a glycosylated protein present in milk at a concentration of 100-200 mg/L. It is an enzyme important for fat digestion in the newborn infant. The protein backbone contains one possible site for N-glyeosylation and several sites for 0-glyeosylation. The glycosylation of BSSL may be important for protection against proteolytic degradation and/or secretion of BSSL. The oligosaeeharides bound to BSSL may also, together with other protein-bound oligosacchatides and free oligosaecharides in milk, play an important role in the defense against pathogenic microorganisms. Human milk contains approximately 5-20 g/L of free milk oligosacchatides, and more than 100 different structures have been identified. There are individual differences in the content of milk oligosaeeharides depending on Lewis and seeretor status.Milk samples were collected from healthy donors at different times during lactation. BSSL was purified from the milk of five donors. Structural characterization of BSSL glyeosylation was performed by high-performance anionexchange chromatography (HP AEC), Bio-Gel P-4 chromatography, lectin affinity chromatography, gas chromatography coupled to mass-spectrometry (MS) and mattix assisted laser desorption-ionization time-of-flight MS. Certain carbohydrate epitopes were detected by monoclonal antibodies and lectins. Some of the methods above were used in combination with ptior derivatization, desialylation or digestion with different exo- and endoglycosidases. Thirteen major free oligosaccharides were quantified in milk from five individuals. Free milk oligosacchatides were purified by P4-Gel chromatography and analyzed by HPAEC.HP AEC coupled to pulsed amperometric detection is extensively used for analysis and quantification of oligosaccharides. Separation is achieved using highly alkaline conditions that lead to ionization of some of the hydroxyl groups, which can then interact with the anion-exchange matrix. The effect of colunm temperature was examined in a range of 13 to 40 oC. A large variation in retention times was found depending on small differences in colunm temperature. Moreover, individual oligosaccharides did not show the same temperature dependence. By use of different column temperatures, HP AEC could be optimized for analysis of milk oligosaccharides.BSSL was found to contain approximately one N-linked and nine O-linked oligosaccharides. The 0-glycans were stmcturally heterogeneous and contained· fucose and/or sialic acid. Each 0-glycan contained an average of eight monosaccharide units. The major N-linked oligosaccharides on human BSSL were mono-sialylated biantennary complex type structures with or without one, two or three fucose residues.Recombinant human BSSL expressed in CHO and C-127 cells were analyzed and found to be differently glycosylated than native BSSL. In contrast to native BSSL, recombinant BSSL did not contain fucose. On BSSL expressed in C-127 cells, the O-glycans were shorter and more extensively sialylated than O-glycans on native BSSL. The majority of N-linked oligosaccharides on recombinant BSSL had the same core structure (biantennary complex type) as native BSSL.Glycosylation of BSSL changed during lactation. BSSL had a higher carbohydrate and sialic acid content in the first lactation month. There was also a shift from preferentially α2-6 to α2-3 linked sialic acid on the protein-bound oligosaccharides during lactation. This shift was also found for free sialylated milk oligosaccharides, and suggests a change in the activity of certain sialyltransferases during lactation.A gradual increase in the expression of the fucosylated carbohydrate epitope Lewis x (Galß1-4[Fucal-3]GlcNAc-) was found on BSSL during the whole lactation period. This was reflected in a higher relative amount of fucosylated N-linked oligosaccharides present on BSSL later in lactation. A similar increase in fucosylation was indicated by analysis of free milk oligosaccharides. One of the major milk oligosaccharides, 3-fucosyllactose (3-FL), also increased in concentration during lactation. However, lacto-N-fucopentaose (LNFIII), the only free milk oligosaccharide containing the Lewis x epitope, showed a constant concentration. This finding does not exclude the possibility that the same fucosyltransferase is involved in the synthesis of Lewis x on BSSL, 3-FL and LNFIII. The precursor of LNFIII, lacto-N-neotetraose (LNnT) showed a marked decrease during lactation, which may explain the different pattem found for LNFIIl. The increase of 3-FL and Lewis x on BSSL was found for all individuals. The other free oligosaccharides studied decreased during lactation, except for lacto-N-fucopentaose li (LNFII), lacto-di-fucotetraose (LDFT) and 3-sialyllactose (3-SL), which showed constant concentrations.Total fucosyltransferase activity decreased during lactation in milk from both secretors and non-secretors. The specific α1-3 fucosyl transferase activity toward lactose also decreased during lactation, which indicated that fucosyltransferase activity in milk does not reflect the activity in the mammary epithelial cells.In conclusion, there are changes in glycosylation during lactation, which involves both protein-bound and free milk oligosaccharides. The different patterns for individual oligosaccharides indicate both down and up regulation of certain glycosyltransferases in the mammary gland during lactation. The importance of these changes for the infant's adaptation to the environment remains to be elucidated.
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23.
  • Landberg, Eva, et al. (författare)
  • Glycosylation of Bile-Salt-Stimulated Lipase from Human Milk : Comparison of Native and Recombinant Forms
  • 1997
  • Ingår i: Archives of Biochemistry and Biophysics. - : Elsevier BV. - 0003-9861 .- 1096-0384. ; 344:1, s. 94-102
  • Tidskriftsartikel (refereegranskat)abstract
    • Bile-salt-stimulated lipase (BSSL) is an enzyme present in human milk. BSSL is important for fat digestion in infants. It contains one site for N-glycosylation and a serine/threonine-rich domain which is highly O-glycosylated. Both N- and O-linked sugar chains were studied on native BSSL from three donors and compared to the glycosylation of recombinant BSSL produced in Chinese hamster ovary or mouse fibroblast (C-127) cell lines. The carbohydrate composition of oligosaccharides was mapped using sugar and methylation analyses, enzyme-linked immunosorbant assay, and different separation techniques. Native BSSL was found to be highly glycosylated (19–26%). It contained a high amount of fucosylated oligosaccharides and expressed both Lewis a and Lewis b blood group antigens. None of the recombinant BSSL forms contained fucose. N-linked structures on native BSSL were identified as mainly mono- and disialylated biantennary complex type structures with or without fucose substitution. High-pH anion-exchange chromatography analysis indicated that the recombinant forms of BSSL contained similar types ofN-glycan structures differing mainly in their content of sialic acid and by the absence of fucose residues. Native BSSL contained predominantly large O-linked oligosaccharides. This was in contrast to the recombinant forms of BSSL which contained mainly short typeO-glycans with a high content of sialic acid. Interestingly, the estimated number of O-glycans attached to native BSSL was lower than that for the recombinant forms.
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24.
  • Landberg, Eva, et al. (författare)
  • Quantitative changes of fucosylated human milk oligosaccharides during lactation in comparison to milk fucosyltransferase activity
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Human milk contains 7-20 g/L of free oligosaccharides. The oligosaccharides show large variations in size and structure. It has been suggested that milk oligosaccharides can prevent pathogenic microorganisms from attaching to the gastrointestinal epithelium by blocking bacterial adhesins. However, the biological role of milk oligosaccharides is far from understood. In this study, the major fucosylated oligosaccharides in milk were followed during six to nine months of lactation. Individual oligosaccharides were separated and quantified by high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD). The fucosylated oligosaccharides 2-fucosyl lactose, lacto-N-fucopentaose I and lacto-N-di-fucohexaose I showed decreasing concentrations in milk during lactation. The concentrations of lacto-difucotetraose, lacto-N-fucopentaose II and Ill remained constant, while 3-fucosyl lactose (3-FL) showed increasing concentrations during lactation. The increase of 3-FL was found for all individuals independent of secretor status, but did not correlate to milk fucosyltransferase activity when the product 3-FL was measured separately. Instead all individuals showed a decrease in fucosyltransferase activity during lactation, indicating that fucosyltransferase activity in milk does not reflect the biosynthetic activity in the mammary gland. This study shows that the composition of fucosylated oligosaccharides vary considerably during the first six months of lactation. This may reflect unique biological roles of certain oligosaccharides in the infant's adaptation to the environment.
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25.
  • Landberg, Eva, et al. (författare)
  • Serum prolactin and macroprolactin in heart failure: no relation to established laboratory or clinical parameters
  • 2011
  • Ingår i: ANNALS OF CLINICAL BIOCHEMISTRY. - : Blackwell Scientific Publications. - 0004-5632. ; 48, s. 51-56
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A few smaller studies have reported that the prolactin concentration is elevated in connection with heart failure. As heart failure is combined with disturbances of several biological systems any or all of which may also influence prolactin concentrations, we wanted to evaluate the relation of prolactin to prognosis in elderly patients. Methods: A total of 462 elderly patients from a primary health-care centre, all with symptoms of heart failure, were included. In addition to clinical examination including echocardiography, concentrations of prolactin, macroprolactin, C-reactive protein, thyroid-stimulating hormone and N-terminal pro B-type natriuretric peptide (NT-proBNP) were measured. Patients were then followed for 10 y, and all incidents of cardiovascular mortality were registered. Results: After excluding patients with macroprolactin, hyperprolactinaemia was found in 3.7% of the patients. There were no differences in prolactin concentrations or in the frequency of macroprolactin between patients with heart failure and those with normal cardiac function, defined as left ventricular ejection fraction of at least 50%. No significant correlation could be found between NT-proBNP and prolactin. Neither could any association be found between cardiovascular mortality and prolactin concentration during 10 y of follow-up. Conclusions: Prolactin concentrations were not associated with cardiovascular mortality or any clinical or biochemical marker of heart failure. Macroprolactin was found in similar frequency among patients with and without heart failure, and showed no correlation with mortality risk.
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26.
  • Landberg, Eva, et al. (författare)
  • Temperature effects in high-performance anion-exchange chromatography of oligosaccharides
  • 1998
  • Ingår i: Journal of Chromatography A. - 0021-9673 .- 1873-3778. ; 814:1-2, s. 97-104
  • Tidskriftsartikel (refereegranskat)abstract
    • High-performance anion-exchange chromatography (HPAEC) with pulsed amperometric detection has been widely used for analysis of mono-, oligo- and polysaccharides. Many factors that affect separation of carbohydrates by HPAEC have been evaluated, however effect of temperature has not been carefully studied. In the present study, neutral and sialylated oligosaccharides from human milk and different types of N-linked oligosaccharides were analysed by HPAEC at temperatures ranging from 13 to 30°C. N-Acetyl neuraminic acid, galacturonic acid and stachyose were also analysed since they have been used as internal standards when analysing various oligosaccharides by HPAEC. All oligosaccharides showed decreased retention times with increased temperature. Even small differences in temperature (i.e. ±5°) resulted in considerable changes in retention times. In addition, individual oligosaccharides showed different relative changes in retention time with increased temperature. By changing the temperature, a switch in elution order of individual oligosaccharides were sometimes found. These results show that retention times relative to an internal standard cannot be used for oligosaccharide identification unless temperature is carefully controlled. Regulation of temperature is also a valuable tool in achieving optimal separation of oligosaccharides by HPAEC.
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27.
  • Landberg, Katarina, et al. (författare)
  • MS1/MMD1 homologues in the moss Physcomitrium patens are required for male and female gametogenesis
  • 2022
  • Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 236, s. 512-524
  • Tidskriftsartikel (refereegranskat)abstract
    • The Arabidopsis Plant HomeoDomain (PHD) proteins AtMS1 and AtMMD1 provide chromatin-mediated transcriptional regulation essential for tapetum-dependent pollen formation. This pollen-based male gametogenesis is a derived trait of seed plants. Male gametogenesis in the common ancestors of land plants is instead likely to have been reminiscent of that in extant bryophytes where flagellated sperms are produced by an elaborate gametophyte generation. Still, also bryophytes possess MS1/MMD1-related PHD proteins. We addressed the function of two MS1/MMD1-homologues in the bryophyte model moss Physcomitrium patens by the generation and analysis of reporter and loss-of-function lines. The two genes are together essential for both male and female fertility by providing functions in the gamete-producing inner cells of antheridia and archegonia. They are furthermore expressed in the diploid sporophyte generation suggesting a function during sporogenesis, a process proposed related by descent to pollen formation in angiosperms. We propose that the moss MS1/MMD1-related regulatory network required for completion of male and female gametogenesis, and possibly for sporogenesis, represent a heritage from ancestral land plants.
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28.
  • Landberg, Katarina, et al. (författare)
  • Studies of moss reproductive development indicate that auxin biosynthesis in apical stem cells may constitute an ancestral function for focal growth control
  • 2020
  • Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 229, s. 845-860
  • Tidskriftsartikel (refereegranskat)abstract
    • The plant hormone auxin is a key factor for regulation of plant development, and this function was probably reinforced during the evolution of early land plants. We have extended the available toolbox to allow detailed studies of how auxin biosynthesis and responses are regulated in moss reproductive organs, their stem cells and gametes to better elucidate the function of auxin in the morphogenesis of early land plants. We measured auxin metabolites and identified IPyA (indole-3-pyruvic acid) as the main biosynthesis pathway inPhyscomitrium(Physcomitrella)patensand established knock-out, overexpressor and reporter lines for biosynthesis genes which were analyzed alongside previously reported auxin-sensing and transport reporters. Vegetative and reproductive apical stem cells synthesize auxin. Sustained stem cell activity depends on an inability to sense the auxin produced while progeny of the stem cells respond to the auxin, aiding in the control of cell division, expansion and differentiation. Gamete precursors are dependent on a certain degree of auxin sensing, while the final differentiation is a low auxin-sensing process. Tha data presented indicate that low auxin activity may represent a conserved hallmark of land plant gametes, and that local auxin biosynthesis in apical stem cells may be part of an ancestral mechanism to control focal growth.
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29.
  • Landberg, Katarina, et al. (författare)
  • The Moss Physcomitrella patens Reproductive Organ Development Is Highly Organized, Affected by the Two SHI/STY Genes and by the Level of Active Auxin in the SHI/STY Expression Domain
  • 2013
  • Ingår i: Plant Physiology. - : Oxford University Press (OUP). - 1532-2548 .- 0032-0889. ; 162:3, s. 1406-1419
  • Tidskriftsartikel (refereegranskat)abstract
    • In order to establish a reference for analysis of the function of auxin and the auxin biosynthesis regulators SHORT INTERNODE/STYLISH (SHI/STY) during Physcomitrella patens reproductive development, we have described male (antheridial) and female (archegonial) development in detail, including temporal and positional information of organ initiation. This has allowed us to define discrete stages of organ morphogenesis and to show that reproductive organ development in P. patens is highly organized and that organ phyllotaxis differs between vegetative and reproductive development. Using the PpSHI1 and PpSHI2 reporter and knockout lines, the auxin reporters GmGH3(pro):GUS and PpPINA(pro): GFP-GUS, and the auxin-conjugating transgene PpSHI2(pro):IAAL, we could show that the PpSHI genes, and by inference also auxin, play important roles for reproductive organ development in moss. The PpSHI genes are required for the apical opening of the reproductive organs, the final differentiation of the egg cell, and the progression of canal cells into a cell death program. The apical cells of the archegonium, the canal cells, and the egg cell are also sites of auxin responsiveness and are affected by reduced levels of active auxin, suggesting that auxin mediates PpSHI function in the reproductive organs.
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30.
  • Li, Bo, et al. (författare)
  • Human Milk Oligosaccharides Protect against Necrotizing Enterocolitis by Activating Intestinal Cell Differentiation
  • 2020
  • Ingår i: Molecular Nutrition & Food Research. - : WILEY. - 1613-4125 .- 1613-4133. ; 64:21
  • Tidskriftsartikel (refereegranskat)abstract
    • Scope Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency and currently the leading cause of mortality in preterm infants. Recent studies show that human milk oligosaccharides (HMOs) reduce the frequency and incidence of NEC; however, the molecular mechanisms for their protection are largely unexplored. Methods and results To address this gap, a genome-wide profiling of the intestinal epithelial transcriptome in response to HMOs using RNA-sequencing is performed. It is found that HMOs alter the host transcriptome in 225 unique target genes pertaining to cell proliferation and differentiation, including upregulation of stem cell differentiation marker HMGCS2. To validate these results, differentiation in Caco-2Bbe1 (Caco-2) intestinal cells is verified by Alcian Blue staining and transepithelial electrical resistance (TER) recordings. Furthermore, an in vivo model of NEC is also employed whereby neonatal pups are gavage fed HMOs. Interestingly, HMOs-fed pups show enhanced cell MUC2 differentiation and HMGCS2 expression. Conclusions These findings demonstrate HMOs protect against NEC in part by altering the differentiation of the crypt-villus axis. In addition, this study suggests that pooled HMOs directly induce a series of biological processes, which provide mechanistic insights to how HMOs protect the host intestine.
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31.
  • Lopez Obando, Mauricio, et al. (författare)
  • Dependence on clade II bHLH transcription factors for nursing of haploid products by tapetal-like cells is conserved between moss sporangia and angiosperm anthers
  • 2022
  • Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 235, s. 718-731
  • Tidskriftsartikel (refereegranskat)abstract
    • Clade II basic helix-loop-helix transcription factors (bHLH TFs) are essential for pollen production and tapetal nursing functions in angiosperm anthers. As pollen has been suggested to be related to bryophyte spores by descent, we characterized two Physcomitrium (Physcomitrella) patens clade II bHLH TFs (PpbHLH092 and PpbHLH098), to test if regulation of sporogenous cells and the nursing cells surrounding them is conserved between angiosperm anthers and bryophyte sporangia. We made CRISPR-Cas9 reporter and loss-of-function lines to address the function of PpbHLH092/098. We sectioned and analyzed WT and mutant sporophytes for a comprehensive stage-by-stage comparison of sporangium development. Spore precursors in the P. patens sporangium are surrounded by nursing cells showing striking similarities to tapetal cells in angiosperms. Moss clade II bHLH TFs are essential for the differentiation of these tapetal-like cells and for the production of functional spores. Clade II bHLH TFs provide a conserved role in controlling the sporophytic somatic cells surrounding and nursing the sporogenous cells in both moss sporangia and angiosperm anthers. This supports the hypothesis that such nursing functions in mosses and angiosperms, lineages separated by roughly 450 million years, are related by descent.
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32.
  • Nevander, Sofia, et al. (författare)
  • Comparison of Venous and Capillary Sampling in Oral Glucose Testing for the Diagnosis of Gestational Diabetes Mellitus: A Diagnostic Accuracy Cross-Sectional Study Using Accu-Chek Inform II
  • 2020
  • Ingår i: Diagnostics (Basel). - : MDPI. - 2075-4418. ; 10:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Gestational diabetes mellitus (GDM) is a common complication with negative impacts on mother and child. The primary aim of this study was to examine whether plasma glucose cutoffs for GDM diagnosis based on venous sampling can be replaced by cutoffs based on capillary sampling. A prospective cross-sectional study was performed at an antenatal care clinic including 175 pregnant women undergoing an oral glucose tolerance test (OGTT). Duplicate samples were collected by capillary and venous puncture while fasting and 1 h and 2 h after an OGTT. Both samples were analyzed on Accu-Chek Inform II. The cutoffs for a GDM diagnosis using capillary samples were corrected from 5.1 to 5.3 mmol/L for the fasting sample, from 10.0 to 11.1 mmol/L for the 1 h sample, and from 8.5 to 9.4 mmol/L for the 2-h sample using half of the dataset. Applying these cutoffs to the remaining dataset resulted in a sensitivity, specificity, and accuracy of 85.0%, 95.0%, and 90.3%, respectively, with a positive predictive value (PPV) of 83%, an negative predictive value (NPV) of 96%, and a positive negative likelihood ratio (LHR) of 16.4 using capillary sampling for the GDM diagnosis at fasting and 2-h after. Corrected cutoffs and capillary samples can be used for the diagnosis of GDM with maintained diagnostic accuracy using Accu-Chek Inform II.
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33.
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34.
  • Nybacka, Sanna, et al. (författare)
  • Carotenoids and alkylresorcinols as objective biomarkers of diet quality when assessing the validity of a web-based food record tool and a food frequency questionnaire in a middle-aged population
  • 2016
  • Ingår i: BMC Nutrition. - : Springer Science and Business Media LLC. - 2055-0928. ; 2:53
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundRecently, two web-based dietary assessment tools were developed; a 4-day food record tool (the Riksmaten method), and a food frequency questionnaire (MiniMeal-Q). The aim of this study was to use objective biomarkers to examine the ability of the two methods to capture habitual dietary intake.MethodsIn total, 200 individuals from the pilot study of the Swedish CArdioPulmonary bioImage Study (SCAPIS) participated. Plasma concentration of carotenoids were determined with high-performance liquid chromatography (HPLC) and used as biomarkers of fruit and vegetable intake. A gas chromatography mass spectrometry (GC-MS) method was used to quantify alkylresorcinol homologues, which were used as biomarkers of whole grain wheat and rye intake.ResultsThe correlations between energy-adjusted fruit and vegetable intakes and plasma carotenoid concentrations (except lycopene) were stronger amongst women than men (r = 0.46 and r = 0.20 for the Riksmaten method, and r = 0.50 and r = 0.31 for MiniMeal-Q, respectively). For whole grains, the correlations of energy-adjusted intakes and alkylresorcinols were higher using the Riksmaten method (r = 0.30 and r = 0.29 for women and men) than the MiniMeal-Q (r = 0.25 and r = 0.20, respectively). In regression analyses between plasma carotenoids (except lycopene) and reported intake of fruits and vegetables, the R2 were 21.6 % and 5.1 % for women and men by the Riksmaten method, and correspondingly, 18.0 % and 6.6 % by the MiniMeal-Q. In the final full models, adjusted for smoking and BMI, all regression models remained statistically significant. The regression analyses of plasma alkylresorcinols and reported intake of whole grains showed an R2 of 9.4 % and 9.7 % for women and men by the Riksmaten method, and correspondingly, 5.3 % and 8.4 % by the MiniMeal-Q. In the final full models, adjusted for smoking and age, all regression models remained statistically significant, except for women in MiniMeal-Q.ConclusionBoth dietary assessment methods were able to capture dietary intake based on food groups with a similar precision. Agreements with objective biomarkers ranged from low to moderate, depending on sex and diet quality indicator. While the ability to capture whole grain intake was weak for both methods and sexes, the assessment of vegetable and fruit intake performed in a satisfactory manner for women in both methods.
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35.
  • Parenmark, Anna, et al. (författare)
  • To mix or not to mix venous blood samples collected in vacuum tubes?
  • 2011
  • Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter. - 1434-6621 .- 1437-4331. ; 49:12, s. 2061-2063
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There are recommendations to mix venous blood samples by inverting the tubes immediately after venipuncture. Though mixing allows efficient anticoagulation in plasma tubes and fast initiation of coagulation in serum tubes, the effect on laboratory analyses and risk of haemolysis has not been thoroughly evaluated. less thanbrgreater than less thanbrgreater thanMethods: Venous blood samples were collected by venipuncture in vacuum tubes from 50 patients (10 or 20 patients in each group). Four types of tubes and 18 parameters used in routine clinical chemistry were evaluated. For each patient and tube, three types of mixing strategies were used: instant mixing, no mixing and 5 min of rest followed by mixing. less thanbrgreater than less thanbrgreater thanResults: Most analyses did not differ significantly in samples admitted to different mixing strategies. Plasma lactate dehydrogenase and haemolysis index showed a small but significant increase in samples omitted to instant mixing compared to samples without mixing. However, in one out of twenty non-mixed samples, activated partial thromboplastin time was seriously affected. less thanbrgreater than less thanbrgreater thanConclusions: These results indicate that mixing blood samples after venipuncture is not mandatory for all types of tubes. Instant mixing may introduce interference for those analyses susceptible to haemolysis. However, tubes with liquid-based citrate buffer for coagulation testing should be mixed to avoid clotting.
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36.
  • Prochazkova, Magdalena, et al. (författare)
  • Vegan Diet Is Associated With Favorable Effects on the Metabolic Performance of Intestinal Microbiota: A Cross-Sectional Multi-Omics Study
  • 2022
  • Ingår i: Frontiers in Nutrition. - : Frontiers Media SA. - 2296-861X. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Aim: Plant-based diets are associated with potential health benefits, but the contribution of gut microbiota remains to be clarified. We aimed to identify differences in key features of microbiome composition and function with relevance to metabolic health in individuals adhering to a vegan vs. omnivore diet. Methods: This cross-sectional study involved lean, healthy vegans (n = 62) and omnivore (n = 33) subjects. We assessed their glucose and lipid metabolism and employed an integrated multi-omics approach (16S rRNA sequencing, metabolomics profiling) to compare dietary intake, metabolic health, gut microbiome, and fecal, serum, and urine metabolomes. Results: The vegans had more favorable glucose and lipid homeostasis profiles than the omnivores. Long-term reported adherence to a vegan diet affected only 14.8% of all detected bacterial genera in fecal microbiome. However, significant differences in vegan and omnivore metabolomes were observed. In feces, 43.3% of all identified metabolites were significantly different between the vegans and omnivores, such as amino acid fermentation products p-cresol, scatole, indole, methional (lower in the vegans), and polysaccharide fermentation product short- and medium-chain fatty acids (SCFAs, MCFAs), and their derivatives (higher in the vegans). Vegan serum metabolome differed markedly from the omnivores (55.8% of all metabolites), especially in amino acid composition, such as low BCAAs, high SCFAs (formic-, acetic-, propionic-, butyric acids), and dimethylsulfone, the latter two being potential host microbiome co-metabolites. Using a machine-learning approach, we tested the discriminative power of each dataset. Best results were obtained for serum metabolome (accuracy rate 91.6%). Conclusion: While only small differences in the gut microbiota were found between the groups, their metabolic activity differed substantially. In particular, we observed a significantly different abundance of fermentation products associated with protein and carbohydrate intakes in the vegans. Vegans had significantly lower abundances of potentially harmful (such as p-cresol, lithocholic acid, BCAAs, aromatic compounds, etc.) and higher occurrence of potentially beneficial metabolites (SCFAs and their derivatives).
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37.
  • Rehn, Matilda, et al. (författare)
  • Hypoxic induction of vascular endothelial growth factor regulates murine hematopoietic stem cell function in the low-oxygenic niche.
  • 2011
  • Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 118:6, s. 1534-1543
  • Tidskriftsartikel (refereegranskat)abstract
    • Hypoxia is emerging as an important characteristic of the hematopoietic stem cell (HSC) niche, but the molecular mechanisms contributing to quiescence, self-renewal, and survival remain elusive. Vascular endothelial growth factor A (VEGFA) is a key regulator of angiogenesis and hematopoiesis. Its expression is commonly regulated by hypoxia-inducible factors (HIF) that are functionally induced in low-oxygen conditions and that activate transcription by binding to hypoxia-response elements (HRE). Vegfa is indispensable for HSC survival, mediated by a cell-intrinsic, autocrine mechanism. We hypothesized that a hypoxic HSC microenvironment is required for maintenance or upregulation of Vegfa expression in HSCs and therefore crucial for HSC survival. We have tested this hypothesis in the mouse model Vegfa(δ/δ), where the HRE in the Vegfa promoter is mutated, preventing HIF binding. Vegfa expression was reduced in highly purified HSCs from Vegfa(δ/δ) mice, showing that HSCs reside in hypoxic areas. Loss of hypoxia-regulated Vegfa expression increases the numbers of phenotypically defined hematopoietic stem and progenitor cells. However, HSC function was clearly impaired when assessed in competitive transplantation assays. Our data provide further evidence that HSCs reside in a hypoxic microenvironment and demonstrate a novel way in which the hypoxic niche affects HSC fate, via the hypoxia-Vegfa axis.
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38.
  • Sanchez, Vera Victoria, et al. (författare)
  • Autophagy is required for gamete differentiation in the moss Physcomitrella patens
  • 2017
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8627 .- 1554-8635. ; 13:11, s. 1939-1951
  • Tidskriftsartikel (refereegranskat)abstract
    • Autophagy, a major catabolic process in eukaryotes, was initially related to cell tolerance to nutrient depletion. In plants autophagy has also been widely related to tolerance to biotic and abiotic stresses (through the induction or repression of programmed cell death, PCD) as well as to promotion of developmentally regulated PCD, starch degradation or caloric restriction important for life span. Much less is known regarding its role in plant cell differentiation. Here we show that macroautophagy, the autophagy pathway driven by engulfment of cytoplasmic components by autophagosomes and its subsequent degradation in vacuoles, is highly active during germ cell differentiation in the early diverging land plant Physcomitrella patens. Our data provide evidence that suppression of ATG5-mediated autophagy results in reduced density of the egg cell-mediated mucilage that surrounds the mature egg, pointing toward a potential role of autophagy in extracellular mucilage formation. In addition, we found that ATG5- and ATG7-mediated autophagy is essential for the differentiation and cytoplasmic reduction of the flagellated motile sperm and hence for sperm fertility. The similarities between the need of macroautophagy for sperm differentiation in moss and mouse are striking, strongly pointing toward an ancestral function of autophagy not only as a protector against nutrient stress, but also in gamete differentiation.
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39.
  • Sanchez, Vera Victoria, et al. (författare)
  • The Physcomitrium patens egg cell expresses several distinct epigenetic components and utilizes homologues of BONOBO genes for cell specification
  • 2022
  • Ingår i: New Phytologist. - : John Wiley & Sons. - 0028-646X .- 1469-8137. ; 233:6, s. 2614-2628
  • Tidskriftsartikel (refereegranskat)abstract
    • Although land plant germ cells have received much attention, knowledge about their specification is still limited. We thus identified transcripts enriched in egg cells of the bryophyte model species Physcomitrium patens, compared the results with angiosperm egg cells, and selected important candidate genes for functional analysis. We used laser-assisted microdissection to perform a cell-type-specific transcriptome analysis on egg cells for comparison with available expression profiles of vegetative tissues and male reproductive organs. We made reporter lines and knockout mutants of the two BONOBO (PbBNB) genes and studied their role in reproduction. We observed an overlap in gene activity between bryophyte and angiosperm egg cells, but also clear differences. Strikingly, several processes that are male-germline specific in Arabidopsis are active in the P. patens egg cell. Among those were the moss PbBNB genes, which control proliferation and identity of both female and male germlines. Pathways shared between male and female germlines were most likely present in the common ancestors of land plants, besides sex-specifying factors. A set of genes may also be involved in the switches between the diploid and haploid moss generations. Nonangiosperm gene networks also contribute to the specification of the P. patens egg cell.
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40.
  • Thelander, Mattias, et al. (författare)
  • Auxin-mediated developmental control in the moss Physcomitrella patens
  • 2018
  • Ingår i: Journal of Experimental Botany. - : Oxford University Press (OUP). - 0022-0957 .- 1460-2431. ; 69, s. 277-290
  • Forskningsöversikt (refereegranskat)abstract
    • The signalling molecule auxin regulates many fundamental aspects of growth and development in plants. We review and discuss what is known about auxin-regulated development in mosses, with special emphasis on the model species Physcomitrella patens. It is well established that mosses and other early diverging plants produce and respond to auxin. By sequencing the P. patens genome, it became clear that it encodes many core proteins important for auxin homeostasis, perception, and signalling, which have also been identified in flowering plants. This suggests that the auxin molecular network was present in the last common ancestor of flowering plants and mosses. Despite fundamental differences in their life cycles, key processes such as organ initiation and outgrowth, branching, tropic responses, as well as cell differentiation, division, and expansion appear to be regulated by auxin in the two lineages. This knowledge paves the way for studies aimed at a better understanding of the origin and evolution of auxin function and how auxin may have contributed to the evolution of land plants.
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41.
  • Thelander, Mattias, et al. (författare)
  • Minimal auxin sensing levels in vegetative moss stem cells revealed by a ratiometric reporter
  • 2019
  • Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 224, s. 775-788
  • Tidskriftsartikel (refereegranskat)abstract
    • Efforts to reveal ancestral functions of auxin, a key regulator of plant growth and development, and its importance for evolution have been hampered by a fragmented picture of auxin response domains in early-diverging land plants. We report the mapping of auxin sensing and responses during vegetative moss development using novel reporters. We established a moss-specific ratiometric reporter (PpR2D2) for Auxin Response Element- and AUXIN RESPONSE FACTOR-independent auxin sensing in Physcomitrella patens, and its readout during vegetative development was compared with new promoter-based GmGH3::GFPGUS and DR5revV2::GFPGUS auxin response reporters. The ratiometric reporter responds rapidly to auxin in a time-, dose- and TRANSPORT INHIBITOR RESISTANT1/AUXIN F-BOX-dependent manner and marks known, anticipated and novel auxin sensing domains. It reveals proximal auxin sensing maxima in filamentous tissues and sensing minima in all five vegetative gametophytic stem cell types as well as dividing cells. PpR2D2 readout is compliant with an ancestral function of auxin as a positive regulator of differentiation vs proliferation in stem cell regions. The PpR2D2 reporter is a sensitive tool for high-resolution mapping of auxin sensing, which can increase our knowledge of auxin function in early-diverging land plants substantially, thereby advancing our understanding of its importance for plant evolution.
  •  
42.
  • Tryggvadottir, Ellen Alma, et al. (författare)
  • Correlation between intake of fish or supplements containing omega-3 fatty acids and early pregnancy plasma concentrations
  • 2022
  • Ingår i: Laeknabladid. - : Laeknabladid/The Icelandic Medical Journal. - 0023-7213 .- 1670-4959. ; 108:5, s. 238-243
  • Tidskriftsartikel (refereegranskat)abstract
    • Long-chain polyunsaturated omega-3 fatty acids are considered important for fetal development, but previous studies suggest suboptimal intake in part of pregnant women in Iceland. The study aim was to evaluate intake of food and supplements containing omega-3 fatty acids, among pregnant women in Iceland and correlations to fatty acid composition in plasma. MATERIALS AND METHODS: Subjects were 853 pregnant women attending their 11-14 weeks ultrasound appointment. Information on intake of food and supplements containing long-chain omega-3 fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) as well as background was obtained by a questionnaire. Blood samples were collected for analysis of plasma fatty acids. Correlation was evaluated using the Spearman correlation. RESULTS: Median intake of lean fish was 1.3 times per week, while fatty fish was consumed once monthly. About 50% of the women took omega-3 containing supplements daily. Higher intake of both fish and omega-3 containing supplements was reflected in higher omega-3 plasma levels (r=0.37 p<0.001). A positive correlation was seen between intake of cod liver oil/capsules (r=0.23, p=0.001), omega-3 oil/capsules (r=0.20, p=0.001) and plasma concentration of omega-3. However, no correlation was seen between intake of a maternal multivitamin containing omega-3 and corresponding plasma concentration (r=0.03, p=0.98). CONCLUSION: Intake of food and supplements containing omega-3 fatty acids was reflected in plasma concentration, except for an Icelandic maternal multivitamin. One third of the women followed the recommendation of eating fish at least twice weekly. About 50% had a daily intake of supplements containing omega-3 fatty acids.
  •  
43.
  • Tryggvadottir, Ellen Alma, et al. (författare)
  • Early pregnancy plasma fatty acid profiles of women later diagnosed with gestational diabetes
  • 2021
  • Ingår i: BMJ Open Diabetes Research and Care. - : BMJ. - 2052-4897. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Fatty acid (FA) concentrations have previously been associated with gestational diabetes mellitus (GDM). However, few studies on GDM have examined FA profiles in early pregnancy or before diagnosis. This study aimed to compare early pregnancy plasma FA profiles of women with and without GDM diagnoses as well as their reported dietary consumption. Research design and methods The subjects comprised 853 women from the prospective study: Pregnant Women in Iceland II (PREWICE II), attending their 11-14 weeks ultrasound appointment in 2017-2018. During the visit, blood samples were collected for plasma FA analysis, and dietary habits were assessed using a short food frequency questionnaire. Information on GDM diagnoses was then later extracted from medical records. Differences in FA profile between GDM cases and non-cases were evaluated using the Mann-Whitney U test. Results GDM was diagnosed in 127 women (14.9%). Concentrations of saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids (PUFA) n-6, PUFA n-3 and total FA were higher in the women who later developed GDM compared with those who did not (p≤0.05). The medians for total FA were 2898 μg/mL for the women with GDM and 2681 μg/mL for those without GDM. Mean adjusted difference for total FA between the groups was 133 μg/mL (95% CI 33 to 233). Similar results were observed in prepregnancy normal-weight women and overweight women/women with obesity. Overall diet quality in early pregnancy appeared to be lower among the women later diagnosed with GDM. Conclusion We found that plasma FA profiles in early pregnancy were different for women later diagnosed with GDM compared with those who were not, independent of the women's body mass index.
  •  
44.
  • Tryggvadottir, Ellen Alma, et al. (författare)
  • Higher Alkylresorcinol Concentrations, a Consequence of Whole-Grain Intake, are Inversely Associated with Gestational Diabetes Mellitus in Iceland
  • 2021
  • Ingår i: Journal of Nutrition. - : Elsevier BV. - 1541-6100 .- 0022-3166. ; 151:5, s. 1159-1166
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: A diet rich in whole grains may provide benefits for pregnant women due to whole grains' high nutritional value and dietary fiber content. OBJECTIVES: To study the associations of whole-grain consumption, as well as the plasma alkylresorcinol concentration, a whole-grain consumption biomarker, in early pregnancy with gestational diabetes mellitus (GDM) diagnoses. METHODS: Subjects were women from the prospective study Pregnant Women in Iceland II (PREWICE II; n = 853) who attended their ultrasound appointment in gestational weeks 11-14 during the period from October 2017 to March 2018. During that visit, whole-grain consumption was estimated using a diet screening questionnaire, and blood samples were collected for analysis of plasma alkylresorcinols (ARs). Information on GDM diagnoses was later extracted from medical records. Multivariate log-binomial regression was used to evaluate the association of dietary whole-grain and AR concentrations with GDM. RESULTS: In total, 14.9% of the women adhered to the national food-based dietary guidelines (n = 127), which recommend 2 portions of whole grains daily. GDM was diagnosed in 127 women (14.9%). The frequency of whole-grain consumption was lower in women who were later diagnosed with GDM compared to the women without GDM (median, 5 times/week vs. 6 times/week, respectively; P = 0.02). This difference was reflected in the lower median concentration of total AR in women diagnosed with GDM (163 nmol/L vs. 209 nmol/L, respectively; P < 0.01). The quartile with the highest concentrations of AR had a RR of 0.50 (95% CI: 0.27-0.90) of being diagnosed with GDM, in comparison to the lowest quartile. There was a significant dose response in the GDM risk with higher AR levels. CONCLUSIONS: We found that a higher consumption of whole grains, reflected both by reported consumption according to the FFQ and AR biomarkers, was associated with a decreased risk of receiving a GDM diagnosis.
  •  
45.
  • Viaene, Tom, et al. (författare)
  • Directional Auxin Transport Mechanisms in Early Diverging Land Plants
  • 2014
  • Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 24, s. 2786-2791
  • Tidskriftsartikel (refereegranskat)abstract
    • The emergence and radiation of multicellular land plants was driven by crucial innovations to their body plans [1]. The directional transport of the phytohormone auxin represents a key, plant-specific mechanism for polarization and patterning in complex seed plants [2-5]. Here, we show that already in the early diverging land plant lineage, as exemplified by the moss Physcomitrella patens, auxin transport by PIN transporters is operational and diversified into ER-localized and plasma membrane-localized PIN proteins. Gain-of-function and loss-of-function analyses revealed that PIN-dependent intercellular auxin transport in Physcomitrella mediates crucial developmental transitions in tip-growing filaments and waves of polarization and differentiation in leaf-like structures. Plasma membrane PIN proteins localize in a polar manner to the tips of moss filaments, revealing an unexpected relation between polarization mechanisms in moss tip-growing cells and multicellular tissues of seed plants. Our results trace the origins of polarization and auxin-mediated patterning mechanisms and highlight the crucial role of polarized auxin transport during the evolution of multicellular land plants.
  •  
46.
  • Wahlberg Topp, Jeanette, et al. (författare)
  • Effects of prolactin on platelet activation and blood clotting
  • 2013
  • Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa Healthcare. - 0036-5513 .- 1502-7686. ; 73:3, s. 221-228
  • Tidskriftsartikel (refereegranskat)abstract
    • Increased levels of prolactin often coincide with an increased risk for thromboembolic events, but it is unclear whether a direct causal relation exists. Our aim was to examine the effect of prolactin on platelet function. In addition to using recombinant prolactin for experiments in vitro, we analyzed platelet function by flow cytometry in a group of 13 females with hyperprolactinaemia and 18 healthy female controls. Platelet activation was measured by P-selectin expression and by the amount of platelet-bound fibrinogen after stimulation with adenosine diphosphate (ADP), collagen-related peptide and the protease activated receptor (thrombin receptor) (PAR)-activating peptides PAR4-AP and PAR1-AP. Free oscillation rheometry was used to measure clotting time in whole blood. No significant effect on platelet activation or clotting time could be seen in in vitro experiments by adding recombinant prolactin. However, significantly lower P-selectin expression was found in the hyperprolactinemic group when platelets were activated by ADP (5 and 10 mu M) or PAR4-AP. The expression of fibrinogen did not differ between the two groups for any of the activators used. For all samples, inverse significant correlations between P-selectin expression and prolactin concentration were found for both 5 mu M ADP (r = 0.61, p andlt; 0.01), 10 mu M ADP (r = -0.62, p andlt; 0.001) and PAR4-AP (r = -0.69, p andlt; 0.001). Thrombin cleavage of recombinant prolactin resulting in a 16 kDa C-terminal fragment did not alter the P-selectin expression upon activation. We found an indirect inhibitory effect of prolactin on platelets in hyperprolactinemic patients, suggesting that prolactin might have a protective role in thromboembolic disease.
  •  
47.
  • Wejryd, Erik, et al. (författare)
  • Low Diversity of Human Milk Oligosaccharides is Associated with Necrotising Enterocolitis in Extremely Low Birth Weight Infants
  • 2018
  • Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 10:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Difference in human milk oligosaccharides (HMO) composition in breast milk may be one explanation why some preterm infants develop necrotizing enterocolitis (NEC) despite being fed exclusively with breast milk. The aim of this study was to measure the concentration of 15 dominant HMOs in breast milk during the neonatal period and investigate how their levels correlated to NEC, sepsis, and growth in extremely low birth weight (ELBW; amp;lt;1000 g) infants who were exclusively fed with breast milk. Milk was collected from 91 mothers to 106 infants at 14 and 28 days and at postmenstrual week 36. The HMOs were analysed with high-performance anion-exchange chromatography with pulsed amperometric detection. The HMOs diversity and the levels of Lacto-N-difucohexaose I were lower in samples from mothers to NEC cases, as compared to non-NEC cases at all sampling time points. Lacto-N-difucohexaose I is only produced by secretor and Lewis positive mothers. There were also significant but inconsistent associations between 3-sialyllactose and 6-sialyllactose and culture-proven sepsis and significant, but weak correlations between several HMOs and growth rate. Our results suggest that the variation in HMO composition in breast milk may be an important factor explaining why exclusively breast milk fed ELBW infants develop NEC.
  •  
48.
  • Wu, Richard You, et al. (författare)
  • Human Milk Oligosaccharides Increase Mucin Expression in Experimental Necrotizing Enterocolitis
  • 2019
  • Ingår i: Molecular Nutrition & Food Research. - : WILEY. - 1613-4125 .- 1613-4133. ; 63:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Scope Necrotizing enterocolitis (NEC) is a leading cause of morbidity and death in preterm infants, occurring more often in formula-fed than breastfed infants. Studies in both rats and humans show that human milk oligosaccharides (HMOs) lower the incidence of NEC, but the mechanism underlying such protection is currently unclear. Methods and Results By extracting HMOs from pooled human breastmilk, the impact of HMOs on the intestinal mucin levels in a murine model of NEC are investigated. To confirm the results, the findings are validated by exposing human intestinal epithelial cells and intestinal organoids to HMOs and evaluated for mucin expression. HMO-gavage to pups increases Muc2 levels and decreases intestinal permeability to macromolecular dextran. HMO-treated cells have increased Muc2 expression, decreased bacterial attachment and dextran permeability during challenge by enteric pathogens. To identify the mediators involved in HMO induction of mucins, it is demonstrated that HMOs directly induce the expression of chaperone proteins including protein disulfide isomerase (PDI). Suppression of PDI activity removes the protective effects of HMOs on barrier function in vitro as well as NEC protection in vivo. Conclusions Taken together, the results provide insights to the possible mechanisms by which HMOs protect the neonatal intestine through upregulation of mucins.
  •  
49.
  • Wu, Richard Y., et al. (författare)
  • Variations in the Composition of Human Milk Oligosaccharides Correlates with Effects on Both the Intestinal Epithelial Barrier and Host Inflammation : A Pilot Study
  • 2022
  • Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 14:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Human milk oligosaccharides are complex, non-digestible carbohydrates that directly interact with intestinal epithelial cells to alter barrier function and host inflammation. Oligosaccharide composition varies widely between individual mothers, but it is unclear if this inter-individual variation has any impact on intestinal epithelial barrier function and gut inflammation. Methods: Human milk oligosaccharides were extracted from the mature human milk of four individual donors. Using an in vitro model of intestinal injury, the effects of the oligosaccharides on the intestinal epithelial barrier and select innate and adaptive immune functions were assessed. Results: Individual oligosaccharide compositions shared comparable effects on increasing transepithelial electrical resistance and reducing the macromolecular permeability of polarized (Caco-2Bbe1) monolayers but exerted distinct effects on the localization of the intercellular tight junction protein zona occludins-1 in response to injury induced by a human enteric bacterial pathogen Escherichia coli, serotype O157:H7. Immunoblots showed the differential effects of oligosaccharide compositions in reducing host chemokine interleukin 8 expression and inhibiting of p38 MAP kinase activation. Conclusions: These results provide evidence of both shared and distinct effects on the host intestinal epithelial function that are attributable to inter-individual differences in the composition of human milk oligosaccharides.
  •  
50.
  • Zamora-Ros, Raul, et al. (författare)
  • Dietary flavonoid, lignan and antioxidant capacity and risk of hepatocellular carcinoma in the European prospective investigation into cancer and nutrition study
  • 2013
  • Ingår i: International Journal of Cancer. - : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 133:10, s. 2429-2443
  • Tidskriftsartikel (refereegranskat)abstract
    • Limited epidemiological evidence suggests a protective role for plant foods rich in flavonoids and antioxidants in hepatocellular cancer (HCC) etiology. Our aim was to prospectively investigate the association between dietary intake of flavonoids, lignans and nonenzymatic antioxidant capacity (NEAC) and HCC risk. Data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort including 477,206 subjects (29.8% male) recruited from ten Western European countries, was analyzed. Flavonoid, lignan and NEAC intakes were calculated using a compilation of existing food composition databases linked to dietary information from validated dietary questionnaires. Dietary NEAC was based on ferric reducing antioxidant capacity (FRAP) and total radical-trapping antioxidant parameter (TRAP). Hepatitis B/C status was measured in a nested case-control subset. During a mean follow-up of 11-years, 191 incident HCC cases (66.5% men) were identified. Using Cox regression, multivariable adjusted models showed a borderline nonsignificant association of HCC with total flavonoid intake (highest versus lowest tertile, HR = 0.65, 95% CI: 0.40-1.04; ptrend  = 0.065), but not with lignans. Among flavonoid subclasses, flavanols were inversely associated with HCC risk (HR = 0.62, 95% CI: 0.39-0.99; ptrend  = 0.06). Dietary NEAC was inversely associated with HCC (FRAP: HR 0.50, 95% CI: 0.31-0.81; ptrend  = 0.001; TRAP: HR 0.49, 95% CI: 0.31-0.79; ptrend  = 0.002), but statistical significance was lost after exclusion of the first 2 years of follow-up. This study suggests that higher intake of dietary flavanols and antioxidants may be associated with a reduced HCC risk.
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