| 1. |
- Sliz, E., et al.
(författare)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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| 2. |
- Tabassum, R, et al.
(författare)
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Genetic architecture of human plasma lipidome and its link to cardiovascular disease
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4329-
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Tidskriftsartikel (refereegranskat)abstract
- Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD.
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| 3. |
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| 4. |
- Ayeni, O. R., et al.
(författare)
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Clinical and Radiographic Criteria Define "Acceptable" Surgical Correction of Hip Femoroacetabular Impingement Syndrome as Well as Postoperative Complications: An International Modified Delphi Study
- 2023
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Ingår i: Arthroscopy-the Journal of Arthroscopic and Related Surgery. - : Elsevier BV. - 0749-8063. ; 39:5, s. 1198-1210
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To develop recommendations for clinical and radiographic criteria to help define the "acceptable" surgical correction of femoroacetabular impingement syndrome (FAIS) and identify/define complications postoperatively. Methods: A 3-phase modified Delphi study was conducted involving a case-based survey; a Likert/multiple choice-based survey concerning radiographic and physical examination characteristics to help define FAIS correction, as well as the prevalence and definition of potential postoperative complications; and 2 consensus meetings. Results: Of the 75 experts invited, 54 completed the Phase I survey, 50 completed the Phase II survey (72% and 67% response rate), and 50 participated in the Phase III consensus meetings. For both typical and atypical (complex) cases, there was consensus that fluoroscopy with multiple views and dynamic hip assessment should be used intraoperatively (96% and 100%, respectively). For typical FAIS cases, the Expert Panel agreed that Dunn lateral and anteroposterior radiographs were the most important radiographs to evaluate the hip postoperatively (88%, consensus). When asked about evaluating the correction of cam impingement postoperatively, 87% voted that they use subjective evaluation of the "sphericity" of the femoral head. In the case of focal and global pincer-type FAIS, there was consensus that the reduction or elimination of the crossover sign (84%) and lateral center-edge angle (91%) were important to inform the extent of the FAIS correction. There was consensus for recommending further investigation at 6 months postoperatively if hip pain had increased/plateaued (92% agreed); that additional investigation and treatment should occur between 6 and 12 months (90% agreed); and that a reoperation may be recommended at 12 months or later following this investigation period (89% agreed). Conclusions: This consensus project identified the importance of using fluoroscopy and dynamic hip assessment intraoperatively; Dunn lateral and anteroposterior view radiographs postoperatively; evaluating the "sphericity" of the femoral head for cam-type correction and the use of dynamic hip assessment; reducing/eliminating the crossover sign for focal pincertype FAIS; evaluating the lateral center-edge angle for global pincer-type FAIS; and avoiding overcorrection of pincer-type FAIS. In cases in which postoperative hip pain increased/plateaued, further investigation and treatment is warranted between 6 and 12 months, and a reoperation may be recommended at a minimum of 12 months depending on the cause of the hip pain. Clinical Relevance: Hip arthroscopy surgeons have yet to reach a firm agreement on what constitutes an "acceptable" or "good" surgery radiographically and how they can achieve desired clinical outcomes. Although this was a comprehensive effort, more study is needed to determine therapeutic thresholds that can be universally applied.
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| 5. |
- Sediva, A, et al.
(författare)
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Europe Immunoglobulin Map
- 2014
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Ingår i: JOURNAL OF CLINICAL IMMUNOLOGY. - : Oxford University Press (OUP). - 0271-9142. ; 178178 Suppl 1, s. 141-143
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Kaasinen, E, et al.
(författare)
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Impact of constitutional TET2 haploinsufficiency on molecular and clinical phenotype in humans
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1252-
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Tidskriftsartikel (refereegranskat)abstract
- Clonal hematopoiesis driven by somatic heterozygous TET2 loss is linked to malignant degeneration via consequent aberrant DNA methylation, and possibly to cardiovascular disease via increased cytokine and chemokine expression as reported in mice. Here, we discover a germline TET2 mutation in a lymphoma family. We observe neither unusual predisposition to atherosclerosis nor abnormal pro-inflammatory cytokine or chemokine expression. The latter finding is confirmed in cells from three additional unrelated TET2 germline mutation carriers. The TET2 defect elevates blood DNA methylation levels, especially at active enhancers and cell-type specific regulatory regions with binding sequences of master transcription factors involved in hematopoiesis. The regions display reduced methylation relative to all open chromatin regions in four DNMT3A germline mutation carriers, potentially due to TET2-mediated oxidation. Our findings provide insight into the interplay between epigenetic modulators and transcription factor activity in hematological neoplasia, but do not confirm the putative role of TET2 in atherosclerosis.
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| 10. |
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| 11. |
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Mattila, Mirjami M., et al.
(författare)
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Androgen and fibroblast growth factor 8 (FGF8) downregulation of thrombospondin 1 (TSP1) in mouse breast cancer cells
- 2006
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 1872-8057 .- 0303-7207. ; 253:1-2, s. 36-43
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Tidskriftsartikel (refereegranskat)abstract
- In the search for androgen target genes responsible for malignant growth in S115 mouse mammary tumor cells we found that thrombospondin 1 (TSP1) expression was strongly downregulated by testosterone (Te). Experiments with cycloheximide suggested that Te repression of TSP1 was dependent on de novo protein synthesis. TSPI repression by Te was preceded by the induction of fibroblast growth factor 8 (FGF8) expression. FGF8 has previously been shown to mediate androgen effects on proliferation of S 115 cells by autocrine/paracrine mechanisms. It has also been shown to increase breast cancer cell growth as tumors in nude mice and to stimulate tumor angiogenesis. We studied here the possibility that FGF8 belonged to the Te-induced de novo synthesized proteins that mediate the effect of Te on TSP1 expression in these cells. We found that addition of FGF8b to in vitro cultures or ectopic expression of FGF8b in S115 cells repressed TSP1 expression at mRNA and protein levels even in the absence of Te. FGF2, another angiogenic member of FGF family, also downregulated TSPI mRNA level in the in vitro cultures of S115 cells. The antisense oligonucleotides for FGF8 did not, however, prevent Te-repression of TSP1 mRNA expression and a neutralizing anti-FGF8b antibody only partially opposed Te induced downregulation of TSP1. These results suggest that both androgen and FGF8 inhibit TSP1 expression independently. They also suggest that opposite to many other androgen-induced responses in S115 cells, the effect of Te on the expression TSP1 is not mediated by FGF8.
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| 16. |
- Sentenac, M, et al.
(författare)
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Maternal education and language development at 2 years corrected age in children born very preterm: results from a European population-based cohort study
- 2020
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Ingår i: Journal of epidemiology and community health. - : BMJ. - 1470-2738 .- 0143-005X. ; 74:4, s. 346-353
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Tidskriftsartikel (refereegranskat)abstract
- Socioeconomic factors influence language development in the general population, but the association remains poorly documented in children born very preterm (VPT). We assessed the impact of maternal education on language development in children born VPT and effect modification by perinatal risk.MethodsData were from the Effective Perinatal Intensive Care in Europe (EPICE) population-based cohort of children born <32 weeks’ gestational age (GA) in 2011/2012. Regions from six countries (Estonia, France, Germany, Italy, Sweden and UK) used a validated short form MacArthur Developmental Communicative Inventories Checklist to assess language at 2 years corrected age. Perinatal variables were collected from clinical records. We assessed expressive language delay (ELD), defined as (a) not combining words; and (b) expressive vocabulary <10th percentile of norms for age and sex. Perinatal risk (low, moderate and high) was determined using GA, small for GA and neonatal morbidities. We estimated adjusted risk ratios (aRR) of ELD by maternal education with inverse weighting to account for non-response bias.ResultsOf 2741 children, 24.6% were not combining words and 39.7% had a low expressive vocabulary. Low maternal education (lower secondary or less compared with a bachelor’s degree or more) increased risks of ELD: not combining words: aRR=1.52 (95% CI 1.36 to 1.69); low expressive vocabulary: aRR=1.25 (1.04 to 1.51). For children with low perinatal risk, the aRR were 1.88 (1.26 to 2.80) and 1.44 (1.06 to 1.95), respectively, compared with those with high perinatal risks: 1.36 (1.10 to 1.67) and 1.11 (0.97 to 1.27), respectively.ConclusionLow maternal education affects ELD for children born VPT, although the association appears attenuated among those with highest perinatal risk.
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| 17. |
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| 18. |
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| 19. |
- Elo, Teresa D., et al.
(författare)
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Stromal Activation Associated with Development of Prostate Cancer in Prostate-Targeted Fibroblast Growth Factor 8b Transgenic Mice
- 2010
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Ingår i: Neoplasia. - : Elsevier BV. - 1522-8002 .- 1476-5586. ; 12:11, s. 94-915
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Tidskriftsartikel (refereegranskat)abstract
- Expression of fibroblast growth factor 8 (FGF-8) is commonly increased in prostate cancer. Experimental studies have provided evidence that it plays a role in prostate tumorigenesis and tumor progression. To study how increased FGF-8 affects the prostate, we generated and analyzed transgenic (TG) mice expressing FGF-8b under the probasin promoter that targets expression to prostate epithelium. Prostates of the TG mice showed an increased size and changes in stromal and epithelial morphology progressing from atypia and prostatic intraepithelial neoplasia (mouse PIN, mPIN) lesions to tumors with highly variable phenotype bearing features of adenocarcinoma, carcinosarcoma, and sarcoma. The development of mPIN lesions was preceded by formation of activated stroma containing increased proportion of fibroblastic cells, rich vasculature, and inflammation. The association between advancing stromal and epithelial alterations was statistically significant. Microarray analysis and validation with quantitative polymerase chain reaction revealed that expression of osteopontin and connective tissue growth factor was markedly upregulated in TG mouse prostates compared with wild type prostates. Androgen receptor staining was decreased in transformed epithelium and in hypercellular stroma but strongly increased in the sarcoma-like lesions. In conclusion, our data demonstrate that disruption of FGF signaling pathways by increased epithelial production of FGF-8b leads to strongly activated and atypical stroma, which precedes development of mPIN lesions and prostate cancer with mixed features of adenocarcinoma and sarcoma in the prostates of TG mice. The results suggest that increased FGF-8 in human prostate may also contribute to prostate tumorigenesis by stromal activation.
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| 20. |
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| 21. |
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| 22. |
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| 23. |
- Johansson, BL, et al.
(författare)
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C-peptide improves adenosine-induced myocardial vasodilation in type 1 diabetes patients
- 2004
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Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 286:1, s. E14-E19
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Tidskriftsartikel (refereegranskat)abstract
- Patients with type 1 (insulin-dependent) diabetes show reduced skeletal muscle blood flow and coronary vasodilatory function despite intensive insulin therapy and good metabolic control. Administration of proinsulin C-peptide increases skeletal muscle blood flow in these patients, but a possible influence of C-peptide on myocardial vasodilatory function in type 1 diabetes has not been investigated. Ten otherwise healthy young male type 1 diabetic patients (Hb A1c 6.6%, range 5.7-7.9%) were studied on two consecutive days during normoinsulinemia and euglycemia in a double-blind, randomized, crossover design, receiving intravenous infusion of C-peptide (5 pmol·kg-1·min-1) for 120 min on one day and saline infusion on the other day. Myocardial blood flow (MBF) was measured at rest and during adenosine administration (140 μg·kg-1·min-1) both before and during the C-peptide or saline infusions by use of positron emission tomography and [15O]H2O administration. Basal MBF was not significantly different in the patients compared with an age-matched control group, but adenosine-induced myocardial vasodilation was 30% lower ( P < 0.05) in the patients. During C-peptide administration, adenosine-stimulated MBF increased on average 35% more than during saline infusion ( P < 0.02) and reached values similar to those for the healthy controls. Moreover, as evaluated from transthoracal echocardiographic measurements, C-peptide infusion resulted in significant increases in both left ventricular ejection fraction (+5%, P < 0.05) and stroke volume (+7%, P < 0.05). It is concluded that short-term C-peptide infusion in physiological amounts increases the hyperemic MBF and left-ventricular function in type 1 diabetic patients.
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| 24. |
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| 25. |
- Keskitalo, S, et al.
(författare)
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Dominant TOM1 mutation associated with combined immunodeficiency and autoimmune disease
- 2019
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Ingår i: NPJ genomic medicine. - : Springer Science and Business Media LLC. - 2056-7944. ; 4, s. 14-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Mutations in several proteins functioning as endolysosomal components cause monogenic autoimmune diseases, of which pathogenesis is linked to increased endoplasmic reticulum stress, inefficient autophagy, and defective recycling of immune receptors. We report here a heterozygous TOM1 p.G307D missense mutation, detected by whole-exome sequencing, in two related patients presenting with early-onset autoimmunity, antibody deficiency, and features of combined immunodeficiency. The index patient suffered from recurrent respiratory tract infections and oligoarthritis since early teens, and later developed persistent low-copy EBV-viremia, as well as an antibody deficiency. Her infant son developed hypogammaglobulinemia, autoimmune enteropathy, interstitial lung disease, profound growth failure, and treatment-resistant psoriasis vulgaris. Consistent with previous knowledge on TOM1 protein function, we detected impaired autophagy and enhanced susceptibility to apoptosis in patient-derived cells. In addition, we noted diminished STAT and ERK1/2 signaling in patient fibroblasts, as well as poor IFN-γ and IL-17 secretion in T cells. The mutant TOM1 failed to interact with TOLLIP, a protein required for IL-1 recycling, PAMP signaling and autophagosome maturation, further strengthening the link between the candidate mutation and patient pathophysiology. In sum, we report here an identification of a novel gene, TOM1, associating with early-onset autoimmunity, antibody deficiency, and features of combined immunodeficiency. Other patient cases from unrelated families are needed to firmly establish a causal relationship between the genotype and the phenotype.
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| 26. |
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| 27. |
- Moller, Anders Pape, et al.
(författare)
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Clutch-size variation in Western Palaearctic secondary hole-nesting passerine birds in relation to nest box design
- 2014
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Ingår i: Methods in Ecology and Evolution. - 2041-210X. ; 5:4, s. 353-362
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Tidskriftsartikel (refereegranskat)abstract
- Secondary hole-nesting birds that do not construct nest holes themselves and hence regularly breed in nest boxes constitute important model systems for field studies in many biological disciplines with hundreds of scientists and amateurs involved. Those research groups are spread over wide geographic areas that experience considerable variation in environmental conditions, and researchers provide nest boxes of varying designs that may inadvertently introduce spatial and temporal variation in reproductive parameters. We quantified the relationship between mean clutch size and nest box size and material after controlling for a range of environmental variables in four of the most widely used model species in the Western Palaearctic: great tit Parus major, blue tit Cyanistes caeruleus, pied flycatcher Ficedula hypoleuca and collared flycatcher F.albicollis from 365 populations and 79610 clutches. Nest floor area and nest box material varied non-randomly across latitudes and longitudes, showing that scientists did not adopt a random box design. Clutch size increased with nest floor area in great tits, but not in blue tits and flycatchers. Clutch size of blue tits was larger in wooden than in concrete nest boxes. These findings demonstrate that the size of nest boxes and material used to construct nest boxes can differentially affect clutch size in different species. The findings also suggest that the nest box design may affect not only focal species, but also indirectly other species through the effects of nest box design on productivity and therefore potentially population density and hence interspecific competition.
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| 28. |
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| 29. |
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| 30. |
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| 31. |
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| 32. |
- van Bodegraven, Eduard A., et al.
(författare)
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Minimally invasive robot-assisted and laparoscopic distal pancreatectomy in a pan-European registry a retrospective cohort study
- 2024
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Ingår i: International Journal of Surgery. - : LIPPINCOTT WILLIAMS & WILKINS. - 1743-9191 .- 1743-9159. ; 110:6, s. 3554-3561
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Tidskriftsartikel (refereegranskat)abstract
- Background: International guidelines recommend monitoring the use and outcome of minimally invasive pancreatic surgery (MIPS). However, data from prospective international audits on minimally invasive distal pancreatectomy (MIDP) are lacking. This study examined the use and outcome of robot-assisted (RDP) and laparoscopic (LDP) distal pancreatectomy in the E-MIPS registry. Patients and methods: Post-hoc analysis in a prospective audit on MIPS, including consecutive patients undergoing MIDP in 83 centers from 19 European countries (01-01-2019/31-12-2021). Primary outcomes included intraoperative events (grade 1: excessive blood loss, grade 2: conversion/change in operation, grade 3: intraoperative death), major morbidity, and in-hospital/30-day mortality. Multivariable logistic regression analyses identified high-risk groups for intraoperative events. RDP and LDP were compared in the total cohort and high-risk groups. Results: Overall, 1672 patients undergoing MIDP were included; 606 (36.2%) RDP and 1066 (63.8%) LDP. The annual use of RDP increased from 30.5% to 42.6% (P<0.001). RDP was associated with fewer grade 2 intraoperative events compared with LDP (9.6% vs. 16.8%, P<0.001), with longer operating time (238 vs. 201 min, P<0.001). No significant differences were observed between RDP and LDP regarding major morbidity (23.4% vs. 25.9%, P=0.264) and in-hospital/30-day mortality (0.3% vs. 0.8%, P=0.344). Three high-risk groups were identified; BMI greater than 25 kg/m(2), previous abdominal surgery, and vascular involvement. In each group, RDP was associated with fewer conversions and longer operative times. Conclusion: This European registry-based study demonstrated favorable outcomes for MIDP, with mortality rates below 1%. LDP remains the predominant approach, whereas the use of RDP is increasing. RDP was associated with fewer conversions and longer operative time, including in high-risk subgroups. Future randomized trials should confirm these findings and assess cost differences.
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| 33. |
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| 34. |
- Forsman, Jukka T., et al.
(författare)
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Avoiding perceived past resource use of potential competitors affects niche dynamics in a bird community
- 2014
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Ingår i: BMC Evolutionary Biology. - : Springer Science and Business Media LLC. - 1471-2148. ; 14, s. 175-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Social information use is usually considered to lead to ecological convergence among involved con-or heterospecific individuals. However, recent results demonstrate that observers can also actively avoid behaving as those individuals being observed, leading to ecological divergence. This phenomenon has been little explored so far, yet it can have significant impact on resource use, realized niches and species co-existence. In particular, the time-scale and the ecological context over which such shifts can occur are unknown. We examined with a long-term (four years) field experiment whether experimentally manipulated, species-specific, nest-site feature preferences (symbols on nest boxes) are transmitted across breeding seasons and affect future nest-site preferences in a guild of three cavity-nesting birds. Results: Of the examined species, resident great tits (Parus major) preferred the symbol that had been associated with unoccupied nest boxes in the previous year, i.e., their preference shifted towards niche space previously unused by putative competitors and conspecifics. Conclusions: Our results show that animals can remember the earlier resource use of conspecifics and other guild members and adjust own decisions accordingly one year after. Our experiment cannot reveal the ultimate mechanism(s) behind the observed behaviour but avoiding costs of intra-or interspecific competition or ectoparasite load in old nests are plausible reasons. Our findings imply that interspecific social information use can affect resource sharing and realized niches in ecological time-scale through active avoidance of observed decisions and behavior of potentially competing species.
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| 35. |
- Kivela, Sami M., et al.
(författare)
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The past and the present in decision-making : the use of conspecific and heterospecific cues in nest site selection
- 2014
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Ingår i: Ecology. - : Wiley. - 0012-9658 .- 1939-9170. ; 95:12, s. 3428-3439
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Tidskriftsartikel (refereegranskat)abstract
- Nest site selection significantly affects fitness, so adaptations for assessment of the qualities of available sites are expected. The assessment may be based on personal or social information, the latter referring to the observed location and performance of both conspecific and heterospecific individuals. Contrary to large-scale breeding habitat selection, small-scale nest site selection within habitat patches is insufficiently understood. We analyzed nest site selection in the migratory Collared Flycatcher Ficedula albicollis in relation to present and past cues provided by conspecifics and by resident tits within habitat patches by using long-term data. Collared Flycatchers preferred nest boxes that were occupied by conspecifics in the previous year. This preference was strongest in breeding pairs where both individuals bred in the same forest patch in the previous year. The results also suggest preference for nest boxes close to boxes where conspecifics had a high breeding success in the previous year, and for nest boxes which are presently surrounded by a high number of breeding Great Tits Parus major. The results indicate social information use in nest site selection at a small spatial scale, where Collared Flycatchers use conspecific cues with a time lag of one year and heterospecific cues instantly.
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| 36. |
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| 37. |
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| 38. |
- Mylam, Karen Juul, et al.
(författare)
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F-18-fluorodeoxyglucose-positron emission tomography/computed tomography after one cycle of chemotherapy in patients with diffuse large B-cell lymphoma: results of a Nordic/US intergroup study
- 2015
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Ingår i: Leukemia & Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 56:7, s. 2005-2012
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the predictive value of interim positon emission tomography (I-PET) after one course of chemoimmunotherapy in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). One hundred and twelve patients with DLBCL were enrolled. All patients had PET/computed tomography (CT) scans performed after one course of chemotherapy (PET-1). I-PET scans were categorized according to International Harmonization Project criteria (IHP), Deauville 5-point scale (D 5PS) with scores 1-3 considered negative (D 5PS>3) and D 5PS with scores 1-4 considered negative (D 5PS = 5). Ratios of tumor maximum standardized uptake value (SUVmax) to liver SUVmax were also analyzed. We found no difference in progression-free survival (PFS) between PET-negative and PET-positive patients according to IHP and D 5PS>3. The 2-year PFS using D 5PS = 5 was 50.9% in the PET-positive group and 84.8% in the PET-negative group (p = 0.002). A tumor/liver SUVmax cut-off of 3.1 to distinguish D 5PS scores of 4 and 5 provided the best prognostic value. PET after one course of chemotherapy was not able to safely discriminate PET-positive and PET-negative patients in different prognostic groups.
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| 39. |
- Pilvi, Taru-K., et al.
(författare)
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Metabolomic changes in fatty liver can be modified by dietary protein and calcium during energy restriction
- 2008
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Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group Co., Limited. - 1007-9327 .- 2219-2840. ; 14:28, s. 4462-4472
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To characterise the effect of energy restriction (ER) on liver lipid and primary metabolite profile by using metabolomic approach. We also investigated whether the effect of energy restriction can be further enhanced by modification of dietary protein source and calcium.METHODS: Liver metabolomic profile of lean and obese C57Bl/6J mice (n = 10/group) were compared with two groups of weight-reduced mice. ER was performed on control diet and whey protein-based high-calcium diet (whey + Ca). The metabolomic analyses were performed using the UPLC/MS based lipidomic platform and the HPLC/MS/MS based primary metabolite platform.RESULTS: ER on both diets significantly reduced hepatic lipid accumulation and lipid droplet size, while only whey + Ca diet significantly decreased blood glucose (P < 0.001) and serum insulin (P < 0.01). In hepatic lipid species the biggest reduction was in the level of triacylglycerols and ceramides while the level of cholesterol esters was significantly increased during ER. Interestingly, diacylglycerol to phospholipid ratio, an indicator of relative amount of diabetogenic diglyceride species, was increased in the control ER group, but decreased in the whey + Ca ER group (P < 0.001, vs obese). ER on whey + Ca diet also totally reversed the obesity induced increase in the relative level of lipotoxic ceramides (P < 0.001, vs obese; P > 0.05, vs lean). These changes were accompanied with up-regulated TCA cycle and pentose phosphate pathway metabolites.CONCLUSION: ER-induced changes on hepatic metabolomic profile can be significantly affected by dietary protein source. The therapeutic potential of whey protein and calcium should be further studied.
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| 40. |
- Seppanen, AV, et al.
(författare)
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Follow-up after very preterm birth in Europe
- 2022
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Ingår i: Archives of disease in childhood. Fetal and neonatal edition. - : BMJ. - 1468-2052 .- 1359-2998. ; 107:1, s. 113-114
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 41. |
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| 42. |
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| 43. |
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| 44. |
- Seppanen, T., et al.
(författare)
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Deviations from Vegard's rule in Al1-xInxN (0001) alloy thin films grown by magnetron sputter epitaxy
- 2007
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 101:4
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Tidskriftsartikel (refereegranskat)abstract
- Al1-xInxN (0001) thin films of the pseudobinary AlN-InN system were grown epitaxially onto (111)-oriented MgO wafers with seed layers of Ti1-y Zry N by dual direct current magnetron sputtering under ultrahigh vacuum conditions. The relaxed film c -axis lattice parameters determined by x-ray diffraction were studied as a function of composition in the range of 0.07
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| 45. |
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| 46. |
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| 47. |
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| 48. |
- Toivonen, P, et al.
(författare)
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Cavum septum pellucidum and psychopathy
- 2013
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Ingår i: The British journal of psychiatry : the journal of mental science. - : Royal College of Psychiatrists. - 1472-1465. ; 203:2, s. 152-153
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Tidskriftsartikel (refereegranskat)abstract
- The presence of cavum septum pellucidum (CSP) has been reported to be a neurodevelopmental marker of psychopathy. We scanned 26 violent offenders and 25 controls; 2 offenders and 2 controls had CSP (8% in both groups). Thus, the presence of CSP is not a common or a unique feature of antisocial personality disorder or psychopathy.
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| 49. |
- Tuovinen, EA, et al.
(författare)
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Characterization of Expanded Gamma Delta T Cells from Atypical X-SCID Patient Reveals Preserved Function and IL2RG-Mediated Signaling
- 2023
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Ingår i: Journal of clinical immunology. - : Springer Science and Business Media LLC. - 1573-2592 .- 0271-9142. ; 43:2, s. 358-370
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Tidskriftsartikel (refereegranskat)abstract
- Abnormally high γδ T cell numbers among individuals with atypical SCID have been reported but detailed immunophenotyping and functional characterization of these expanded γδ T cells are limited. We have previously reported atypical SCID phenotype caused by hypomorphic IL2RG (NM_000206.3) c.172C > T;p.(Pro58Ser) variant. Here, we have further investigated the index patient’s abnormally large γδ T cell population in terms of function and phenotype by studying IL2RG cell surface expression, STAT tyrosine phosphorylation and blast formation in response to interleukin stimulation, immunophenotyping, TCRvγ sequencing, and target cell killing. In contrast to his ⍺β T cells, the patient’s γδ T cells showed normal IL2RG cell surface expression and normal or enhanced IL2RG-mediated signaling. Vδ2 + population was proportionally increased with a preponderance of memory phenotypes and high overall tendency towards perforin expression. The patient’s γδ T cells showed enhanced cytotoxicity towards A549 cancer cells. His TCRvγ repertoire was versatile but sequencing of IL2RG revealed a novel c.534C > A; p.(Phe178Leu) somatic missense variant restricted to γδ T cells. Over time this variant became predominant in γδ T cells, though initially present only in part of them. IL2RG-Pro58Ser/Phe178Leu variant showed higher cell surface expression compared to IL2RG-Pro58Ser variant in stable HEK293 cell lines, suggesting that somatic p.(Phe178Leu) variant may at least partially rescue the pathogenic effect of germline p.(Pro58Ser) variant. In conclusion, our report indicates that expansion of γδ T cells associated with atypical SCID needs further studying and cannot exclusively be deemed as a homeostatic response to low numbers of conventional T cells.
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- Tuovinen, EA, et al.
(författare)
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Novel Hemizygous IL2RG p.(Pro58Ser) Mutation Impairs IL-2 Receptor Complex Expression on Lymphocytes Causing X-Linked Combined Immunodeficiency
- 2020
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Ingår i: Journal of clinical immunology. - : Springer Science and Business Media LLC. - 1573-2592 .- 0271-9142. ; 40:3, s. 503-514
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Tidskriftsartikel (refereegranskat)abstract
- Hypomorphic IL2RG mutations may lead to milder phenotypes than X-SCID, named variably as atypical X-SCID or X-CID. We report an 11-year-old boy with a novel c. 172C>T;p.(Pro58Ser) mutation in IL2RG, presenting with atypical X-SCID phenotype. We also review the growing number of hypomorphic IL2RG mutations causing atypical X-SCID. We studied the patient’s clinical phenotype, B, T, NK, and dendritic cell phenotypes, IL2RG and CD25 cell surface expression, and IL-2 target gene expression, STAT tyrosine phosphorylation, PBMC proliferation, and blast formation in response to IL-2 stimulation, as well as protein-protein interactions of the mutated IL2RG by BioID proximity labeling. The patient suffered from recurrent upper and lower respiratory tract infections, bronchiectasis, and reactive arthritis. His total lymphocyte counts have remained normal despite skewed T and B cells subpopulations, with very low numbers of plasmacytoid dendritic cells. Surface expression of IL2RG was reduced on his lymphocytes. This led to impaired STAT tyrosine phosphorylation in response to IL-2 and IL-21, reduced expression of IL-2 target genes in patient CD4+ T cells, and reduced cell proliferation in response to IL-2 stimulation. BioID proximity labeling showed aberrant interactions between mutated IL2RG and ER/Golgi proteins causing mislocalization of the mutated IL2RG to the ER/Golgi interface. In conclusion, IL2RG p.(Pro58Ser) causes X-CID. Failure of IL2RG plasma membrane targeting may lead to atypical X-SCID. We further identified another carrier of this mutation from newborn SCID screening, lost to closer scrutiny.
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