| 1. |
- Andersson, Daniel P., et al.
(författare)
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Omentectomy in addition to gastric bypass surgery and influence on insulin sensitivity : A randomized double blind controlled trial
- 2014
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Ingår i: Clinical Nutrition. - : Elsevier BV. - 0261-5614 .- 1532-1983. ; 33:6, s. 991-996
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Tidskriftsartikel (refereegranskat)abstract
- Background & aims: Accumulation of visceral adipose tissue is associated with insulin resistance and cardio-vascular disease. The aim of this study was to elucidate whether removal of a large amount of visceral fat by omentectomy in conjunction with Roux en-Y gastric bypass operation (RYGB) results in enhanced improvement of insulin sensitivity compared to gastric bypass surgery alone. Methods: Eighty-one obese women scheduled for RYGB were included in the study. They were randomized to RYGB or RYGB in conjunction with omentectomy. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp before operation and sixty-two women were also reexamined 2 years post-operatively. The primary outcome measure was insulin sensitivity and secondary outcome measures included cardio-metabolic risk factors. Results: Two-year weight loss was profound but unaffected by omentectomy. Before intervention, there were no clinical or metabolic differences between the two groups. The difference in primary outcome measure, insulin sensitivity, was not significant between the non-omentectomy (6.7 +/- 1.6 mg/kg body weight/minute) and omentectomy groups (6.6 +/- 1.5 mg/kg body weight/minute) after 2 years. Nor did any of the cardio-metabolic risk factors that were secondary outcome measures differ significantly. Conclusion: Addition of omentectomy to gastric bypass operation does not give an incremental effect on long term insulin sensitivity or cardio-metabolic risk factors. The clinical usefulness of omentectomy in addition to gastric bypass operation is highly questionable.
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| 2. |
- Arner, Peter, et al.
(författare)
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Variations in the size of the major omentum are primarily determined by fat cell number
- 2013
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 98:5, s. E897-E901
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Accumulation of visceral adipose tissue (VAT) is strongly linked to insulin resistance. Variations in the size of any adipose depot are determined by alterations in adipocyte volume and/or number. The individual contribution of each of the latter factors was determined in the major omentum, a fully resectable VAT depot.SUBJECTS: Total removal of the major omentum (omentectomy) was performed in conjunction with bariatric surgery in 55 obese patients. Tissue weight as well as mean adipocyte size and number in the omentum were determined. In subgroups, total VAT was estimated by computerized tomography (n = 17) or dual-energy x-ray absorptiometry (n = 34).RESULTS: The weight of the major omentum (on average 0.6 kg) correlated significantly with total VAT mass estimated by computerized tomography or dual-energy x-ray absorptiometry (r = 0.48-0.7; P < .01). Omental weight in relation to total body fat correlated with several features of the metabolic syndrome and inversely with serum-leptin (P < .001). Mean adipocyte size and total adipocyte number correlated strongly with omental weight (r = 0.6-0.8; P < .0001), irrespective of body mass index and total body fat mass, and accounted almost in total for interindividual variations in omental size. However, stepwise regression analysis demonstrated that adipocyte number was significantly (P < .0001) more important (62%) than adipocyte size (35%).CONCLUSION: The size of the major omentum is representative for VAT mass and correlates with a pernicious metabolic profile. Variations in omental weight are primarily determined by adipocyte number and to a lesser degree by adipocyte size, suggesting that increased VAT mass in obesity is predominantly dependent on adipocyte proliferation.
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| 3. |
- Ruber, Roger, et al.
(författare)
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Accelerator development at the FREIA Laboratory
- 2021
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Ingår i: Journal of Instrumentation. - : Institute of Physics Publishing (IOPP). - 1748-0221. ; 16:7
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Tidskriftsartikel (refereegranskat)abstract
- The FREIA Laboratory at Uppsala University focuses on superconducting technology and accelerator development. It actively supports the development of the European Spallation Source, CERN, and MAX IV, among others. FREIA has developed test facilities for superconducting accelerator technology such as a double-cavity horizontal test cryostat, a vertical cryostat with a novel magnetic field compensation scheme, and a test stand for short cryomodules. Accelerating cavities have been tested in the horizontal cryostat, crab-cavities cavities in the vertical cryostat, and cryomodules for ESS on the cryomodule test stand. High power radio-frequency amplifier prototypes based on vacuum tube technology were developed for driving spoke cavities. Solid-state amplifiers and power combiners are under development for future projects. We present the status of the FREIA Laboratory complemented with results of recent projects and future prospects.
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| 4. |
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| 5. |
- Bell, Linda, et al.
(författare)
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The Swedish NICE Corpus – Spoken dialogues between children and embodied characters in a computer game scenario
- 2005
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Ingår i: Proceedings Interspeech 2005 - Eurospeech. - Lisbon, Portugal : ISCA. ; , s. 2765-2768, s. 2765-2768
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Konferensbidrag (refereegranskat)abstract
- This article describes the collection and analysis of a Swedish database of spontaneous and unconstrained children-machine dialogues. The Swedish NICE corpus consists of spoken dialogues between children aged 8 to 15 and embodied fairytale characters in a computer game scenario. Compared to previously collected corpora of children's computer-directed speech, the Swedish NICE corpus contains extended interactions, including three-party conversation, in which the young users used spoken dialogue as the primary means of progression in the game.
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| 6. |
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| 7. |
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| 8. |
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| 9. |
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| 10. |
- Collins, David H., et al.
(författare)
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Gene expression during larval caste determination and differentiation in intermediately eusocial bumblebees, and a comparative analysis with advanced eusocial honeybees
- 2021
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Ingår i: Molecular Ecology. - : John Wiley & Sons. - 0962-1083 .- 1365-294X. ; 30:3, s. 718-735
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Tidskriftsartikel (refereegranskat)abstract
- The queen-worker caste system of eusocial insects represents a prime example of developmental polyphenism (environmentally-induced phenotypic polymorphism) and is intrinsic to the evolution of advanced eusociality. However, the comparative molecular basis of larval caste determination and subsequent differentiation in the eusocial Hymenoptera remains poorly known. To address this issue within bees, we profiled caste-associated gene expression in female larvae of the intermediately eusocial bumblebee Bombus terrestris. In B. terrestris, female larvae experience a queen-dependent period during which their caste fate as adults is determined followed by a nutrition-sensitive period also potentially affecting caste fate but for which the evidence is weaker. We used mRNA-seq and qRT-PCR validation to isolate genes differentially expressed between each caste pathway in larvae at developmental stages before and after each of these periods. We show that differences in gene expression between caste pathways are small in totipotent larvae, then peak after the queen-dependent period. Relatively few novel (i.e. taxonomically-restricted) genes were differentially expressed between castes, though novel genes were significantly enriched in late-instar larvae in the worker pathway. We compared sets of caste-associated genes in B. terrestris with those reported from the advanced eusocial honeybee, Apis mellifera, and found significant but relatively low levels of overlap of gene lists between the two species. These results suggest both the existence of low numbers of shared toolkit genes and substantial divergence in caste-associated genes between Bombus and the advanced eusocial Apis since their last common eusocial ancestor.
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| 11. |
- Gustafson, Joakim, et al.
(författare)
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The NICE fairy-tale game system
- 2004
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Ingår i: Proceedings of the 5th SIGdial Workshop on Discourse and Dialogue at HLT-NAACL 2004. - Boston.
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Konferensbidrag (refereegranskat)abstract
- This paper presents the NICE fairy-tale game system, in which adults and children can interact with various animated characters in a 3D world. Computer games is an interesting application for spoken and multimodal dialogue systems. Moreover, for the development of future computer games, multimodal dialogue has the potential to greatly enrichen the user's experience. In this paper, we also present some requirements that have to be fulfilled to successfully integrate spoken dialogue technology with a computer game application
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| 12. |
- Hedberg, Suzanne, et al.
(författare)
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Comparison of Sleeve Gastrectomy vs Roux-en-Y Gastric Bypass : A Randomized Clinical Trial
- 2024
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Laparoscopic sleeve gastrectomy (SG) and laparoscopic Roux-en-Y gastric bypass (RYGB) are widely used bariatric procedures for which comparative efficacy and safety remain unclear.OBJECTIVE: To compare perioperative outcomes in SG and RYGB.DESIGN, SETTING, AND PARTICIPANTS: In this registry-based, multicenter randomized clinical trial (Bypass Equipoise Sleeve Trial), baseline and perioperative data for patients undergoing bariatric surgery from October 6, 2015, to March 31, 2022, were analyzed. Patients were from university, regional, county, and private hospitals in Sweden (n = 20) and Norway (n = 3). Adults (aged ≥18 years) eligible for bariatric surgery with body mass indexes (BMIs; calculated as weight in kilograms divided by height in meters squared) of 35 to 50 were studied.INTERVENTIONS: Laparoscopic SG or RYGB.MAIN OUTCOMES AND MEASURES: Perioperative complications were analyzed as all adverse events and serious adverse events (Clavien-Dindo grade >IIIb). Ninety-day mortality was also assessed.RESULTS: A total of 1735 of 14 182 eligible patients (12%; 1282 [73.9%] female; mean (SD) age, 42.9 [11.1] years; mean [SD] BMI, 40.8 [3.7]) were included in the study. Patients were randomized and underwent SG (n = 878) or RYGB (n = 857). The mean (SD) operating time was shorter in those undergoing SG vs RYGB (47 [18] vs 68 [25] minutes; P < .001). The median (IQR) postoperative hospital stay was 1 (1-1) day in both groups. The 30-day readmission rate was 3.1% after SG and 4.0% after RYGB (P = .33). There was no 90-day mortality. The 30-day incidence of any adverse event was 40 (4.6%) and 54 (6.3%) in the SG and RYGB groups, respectively (odds ratio, 0.71; 95% CI, 0.47-1.08; P = .11). Corresponding figures for serious adverse events were 15 (1.7%) for the SG group and 23 (2.7%) for the RYGB group (odds ratio, 0.63; 95% CI, 0.33-1.22; P = .19).CONCLUSIONS AND RELEVANCE: This randomized clinical trial of 1735 patients undergoing primary bariatric surgery found that both SG and RYGB were performed with a low perioperative risk without clinically significant differences between groups.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02767505.
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| 13. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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Low dose dehydroepiandrosterone affects behavior in hypopituitary androgen-deficient women: a placebo-controlled trial.
- 2002
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 87:5, s. 2046-52
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Tidskriftsartikel (refereegranskat)abstract
- Thirty-eight women, aged 25-65 yr, with androgen deficiency due to hypopituitarism were treated with oral dehydroepiandrosterone (DHEA; 30 mg/d if <45 yr of age and 20 mg if > or =45 yr of age) for 6 months in a randomized, placebo-controlled, double blind study, followed by a 6-month open treatment period. The administration of DHEA raised the serum levels of DHEAS to normal age-related reference ranges and increased androstenedione and T to subnormal levels. Androgen effects on skin and/or pubic and/or axillary hair were observed in 84% (32 of 38) of the women after all received 6 months of DHEA treatment. No such effects were observed after the placebo treatment. These effects after 6 months were correlated with the serum levels of DHEAS (r = 0.37; P = 0.03), androstenedione (r = 0.42; P = 0.01), and T (r = 0.37; P = 0.03). The percentages of partners who reported improved alertness, stamina, and initiative by their spouses were 70%, 64%, and 55%, respectively, in the DHEA group and 11%, 6%, and 11%, respectively, in the placebo group (P < 0.05). According to the partners, sexual relations tended to improve compared with placebo (P = 0.06). After 6 months of treatment, increased sexual interest or activity was reported by 50% of the women taking 30 mg DHEA, by none taking 20 mg DHEA, and by two women taking placebo (P = NS). Compared with levels after placebo administration, high density lipoprotein cholesterol and apolipoprotein A-1 levels decreased after DHEA. Serum concentrations of IGF-I, serum markers of bone metabolism, and bone density did not change. In conclusion, oral administration of a low dose of DHEA to adult hypopituitary women induced androgen effects on skin and axillary and pubic hair as well as changes in behavior, with only minor effects on metabolism.
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| 14. |
- Johansson, Louise, et al.
(författare)
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Frequency of apical periodontitis in root-filled teeth restored with post and core : A 5-year retrospective study
- 2024
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Ingår i: Clinical and Experimental Dental Research. - : John Wiley & Sons. - 2057-4347. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In conjunction with post placement in root-filled teeth with periapical healthy conditions, root canal retreatment may be performed to improve the seal of the root canal. Whether root canal retreatment for technical reasons (retreatments in teeth without apical periodontitis (AP)) results in lower frequency of AP is unknown.OBJECTIVE: To examine whether there is a difference in frequency of AP between roots with root canals retreated for technical reasons, and roots with root canals not retreated before post placement, with a minimum follow-up of 5 years. Also, to examine changes in root filling quality following root canal retreatment for technical reasons.METHODS: This retrospective study included radiographs of 441 root-filled roots without periapical radiolucencies at baseline, scheduled for post and core treatment. Follow-up data for a minimum of 5 years were available for 305 roots (loss to follow-up 30.8%), 46 of which were retreated for technical reasons. Two calibrated observers assessed root filling sealing quality and length, respectively, and periapical status according to the Periapical Index. The main outcome of the study, AP, was used as the dependent variable and all analyses were performed at root level.RESULTS: The overall frequency of AP at follow-up was 13.8%. The difference in frequency of AP between retreated (4.3%) and nonretreated (15.4%) root canals was not statistically significant, p = .061. Analyses including only roots with preoperatively inadequate root filling quality showed a statistically significant difference (p = .017) between the two treatment groups (2.4% vs. 22.9%).CONCLUSIONS: Root canal retreatment for technical reasons before post and core placement significantly reduces the frequency of AP in roots with inadequate root filling quality.
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| 15. |
- Kald, Anders, et al.
(författare)
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Laparoscopic hernia repair in patients with bilateral groin hernias
- 2000
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Ingår i: European Journal of Surgery. - 1102-4151 .- 1741-9271. ; 166:3, s. 210-212
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare outcome of unilateral and bilateral laparoscopic hernia repair. Design: Prospective consecutive trial. Setting: University hospital, Sweden. Subjects: 380 patients who had unilateral hernias repaired laparoscopically and 64 patients who had bilateral hernias repaired. The median (range) age in the two groups was 56 (21-86) and 61 (30-85) years, respectively and the median (range) follow-up was 42 (24-58) months. Main outcome measures: Operating time, hospital stay, complications, and time to recovery. Results: The median (range) operating time was 70 (25-240) minutes in the unilateral and in the bilateral group 113 (55-330) minutes. The complication rate, recurrence rate, and time to full recovery did not differ between the groups. Conclusion: The laparoscopic approach seems to be a good option for patients with bilateral inguinal hernias.
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| 16. |
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| 17. |
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| 18. |
- Lushnikova, Alexandra, et al.
(författare)
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Patients With Microscopic Colitis Have Altered Levels of Inhibitory and Stimulatory Biomarkers in Colon Biopsies and Sera Compared to Non-inflamed Controls
- 2021
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Ingår i: Frontiers in Medicine. - Lausanne, Switzerland : Frontiers Media S.A.. - 2296-858X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Microscopic colitis (MC) is an inflammatory bowel condition with two subtypes, lymphocytic colitis (LC) and collagenous colitis (CC). Unlike patients with ulcerative colitis (UC) and non-inflamed individuals, MC patients have reduced risk of developing colorectal cancer, possibly due to increased immune surveillance in MC patients.Aim: To examine differences in levels of immunomodulatory molecules, including those involved in immune checkpoint mechanisms, in sera from patients with MC and in colonic biopsies from patients with MC and UC compared with controls.Methods: Using Luminex, 23 analytes (4-1BB, 4-1BBL, APRIL, BAFF, BTLA, CD27, CD28, CD80, CTLA-4, E-cadherin, Galectin-3, GITR, HVEM, IDO, IL-2Rα, LAG-3, MICA, MICB, PD-1, PD-L1, PD-L2, sCD40L and TIM-3) were studied in serum from patients with active MC (n = 35) and controls (n = 23), and in colonic biopsies from patients with active LC (n = 9), active CC (n = 16) and MC in histological remission (LC n = 6, CC n = 6), active UC (n = 15) and UC in remission (n = 12) and controls (n = 58).Results: In serum, IDO, PD-1, TIM-3, 4-1BB, CD27, and CD80 were decreased whereas 4-1BBL and IL-2Rα were increased in MC patients compared with controls. In contrast, in biopsies, levels of PD-L2 and 4-1BB were increased in MC and UC patients with active disease. Furthermore, in biopsies from CC and UC but not LC patients with active disease, CTLA-4, PD-1, APRIL, BAFF, and IL-2Rα were increased compared with controls. PD-L1 was increased in CC but not UC or LC patients. CD27 and TIM-3 were decreased in biopsies from MC patients in comparison to controls whereas levels of MICB were decreased in patients with active UC compared with controls.Conclusions: Compared with non-inflamed controls, levels of soluble and membrane-bound immunomodulatory molecules were systemically and locally altered in MC and UC patients, with most analytes being decreased in serum but enhanced in colonic biopsies. These findings contribute to knowledge about checkpoint molecules and their role as biomarkers in MC and may also contribute to knowledge about possible mechanisms behind the seemingly protective effects of MC against colorectal cancer.
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| 19. |
- Malmberg, Jesper, et al.
(författare)
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Synthesis of aromatic C-xylosides by position inversion of glucose
- 2006
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896. ; 14:19, s. 6659-6665
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Tidskriftsartikel (refereegranskat)abstract
- Two formally C-xylosylated analogs to 2-naphthyl beta-D-xylopyranoside, which is known to initiate priming of glucosaminoglycan chains, were synthesized by a position inversion of glucose (i.e., position I becomes position 5). The D-C-xyloside showed priming, while the L-C-xyloside did not initiate priming. (c) 2006 Elsevier Ltd. All rights reserved.
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| 20. |
- Qvick, Alvida, 1990-, et al.
(författare)
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Circulating miRNA : a biomarker for classification of lung cancer and benign lung disease
- 2019
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Ingår i: Journal of Thoracic Oncology. - : Elsevier. - 1556-0864 .- 1556-1380. ; 14:10, s. 311-311
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background Circulating biomarkers for cancer have great potential for diagnosis as well as follow up of treatment. MicroRNAs (miRNA) are involved in the expression of a majority of proteins with different cell types having different miRNA expression. The aim of this study was to create a circulating miRNA-based model to discriminate patients with lung cancer from patients with benign lung disease. Methods Samples were collected from patients under investigation for lung cancer at Örebro University hospital. Patients were then divided into groups based on diagnosis, which resulted in NSCLC adenocarcinoma (n=24), NSCLC squamous cell carcinoma (n=13), SCLC (n=4) and a heterogeneous group consisting of different benign lung diseases (n=19). Healthy controls were collected separately (n=17). Circulating miRNA was processed using the extraction-free library preparation miRNA Whole Transcriptome Assay with probes for 2083 human mature miRNAs and analyzed with massive parallel sequencing. Differential expression between groups was estimated using edgeR. MiRNAs that had the highest impact on patient grouping were used in a sPLS discriminant analysis. The resulting classification model was validated using the leave-one-out method. Results The final model for comparison between patients with benign lung disease and patients with lung cancer contained 19 miRNAs. The model had an error rate of 15 % with errors distributed evenly between groups. A sub-analysis of patients with mutations in EGFR (n=5) and KRAS (n=6) was performed showing two distinct patterns in miRNA expression. Conclusion MiRNA shows promise as a circulating biomarker for lung cancer but may not be sufficient as an independent classifier. The predictive power may be improved by using several biomarkers in combination. The difference in expression between tumors with different mutations may be derived from alternate driving processes in these tumors.Sequencing results were standardized as counts per million (cpm), miRNA with cpm < 100 was filtered out and quantile normalization and log2 transformation was performed. Differential expression was analyzed using regression model (R software v. 3.5.1, package edgeR v. 3.24.1) with Benjamini-Hochberg correction. The miRNAs that, after correction, had a significant impact on sample groups were kept and analyzed with sparse partial least squares-regression. The resulting model was validated using leave-one-out method.
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| 21. |
- Svensson, Johan, 1964, et al.
(författare)
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Three-years of growth hormone (GH) replacement therapy in GH-deficient adults: effects on quality of life, patient-reported outcomes and healthcare consumption.
- 2004
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Ingår i: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. - : Elsevier BV. - 1096-6374. ; 14:3, s. 207-15
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The objective was to investigate the effects of 3 years of growth hormone (GH) replacement therapy in GH deficient (GHD) patients in Sweden. DESIGN AND PATIENTS: An open label study in 237 adults with GHD (116 men and 121 women), consecutively enrolled in KIMS (Pfizer's international metabolic database) in Sweden. MEASUREMENTS: QoL and healthcare consumption were determined using questionnaires [QoL-assessment of GHD in Adults (QoL-AGHDA), the psychological general well-being (PGWB) index and the patient life situation form (PLSF)]. RESULTS: The mean starting dose of GH was 0.13 mg/day and the mean maintenance dose was 0.37 mg/day. The mean insulin-like growth factor I (IGF-I) SD score increased from -1.92 at baseline to 0.38 after 3 years. There was a sustained increase in QoL as measured by the QoL-AGHDA and PGWB questionnaires. The number of doctor visits and the number of days in hospital were reduced after 3 years of GH replacement. The number of days of sickleave decreased during the first 2 years of treatment, but returned towards baseline values after 3 years. Leisure-time physical activity and satisfaction with physical activity increased. CONCLUSION: Three years of GH replacement therapy induced a sustained improvement in QoL. Healthcare consumption was reduced, although the reduction in the number of days of sickleave was not statistically significant after 3 years of treatment.
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| 22. |
- Van Guelpen, Bethany, et al.
(författare)
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Polymorphisms of methylenetetrahydrofolate reductase and the risk of prostate cancer : a nested case-control study
- 2006
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Ingår i: European Journal of Cancer Prevention. - : Lippincott Williams & Wilkins. - 0959-8278 .- 1473-5709. ; 15:1, s. 46-50
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Tidskriftsartikel (refereegranskat)abstract
- It has been proposed that folate and polymorphisms of the enzyme methylenetetrahydrofolate reductase (MTHFR), which regulates influx of folate from DNA synthesis and repair to methylation reactions, are involved in the aetiology of cancer. To relate the MTHFR 677C→T and 1298A→C polymorphisms to the risk of prostate cancer, taking into consideration prospective plasma levels of folate, vitamin B12 and homocysteine. The design was a case-control study of 223 prostate cancer cases and 435 matched controls nested within the population-based Northern Sweden Health and Disease Cohort. Neither the MTHFR 677C→T nor the MTHFR 1298A→C polymorphism was statistically significantly associated with the risk of prostate cancer in univariate analysis by conditional logistic regression. After adjustment for MTHFR 1298A→C, plasma folate, vitamin B12, homocysteine, body mass index and smoking, the odds ratios were, for the 677 CT genotype, 1.52 [95% confidence interval (CI) 1.02-2.26], and for TT, 0.91 (95% CI 0.41-2.04). Our previously reported observation of a possible increase in the risk of prostate cancer at high plasma folate levels was attributable in this study to subjects having the MTHFR 677C→T polymorphism. We found that the MTHFR 677C→T polymorphism is not likely to have a major role in the development of prostate cancer, although it may possibly increase the risk in combination with high plasma folate levels. Further investigation in larger studies is warranted.
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| 23. |
- Wirén, Anders, 1977-
(författare)
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Correlated selection responses in animal domestication : the behavioural effects of a growth QTL in chickens
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Studying animal domestication offers an opportunity to understand the mechanisms of evolution. Domestication is associated with a change in selection pressures; selection for production traits is introduced, and animals are faced with larger and denser social groups. It is not unexpected then that domestication produces a simultaneous change in a number of traits, both physiological and behavioural. This correlated change in traits, e.g. egg production and social behaviour has been termed the “domestic phenotype”. However, it has been shown that selection for one trait alone among the many associated with the domestic phenotype can lead to simultaneous changes in others. This may be a result of such traits being inherited together because of pleiotropy or close linkage of several genes affecting different traits. A chicken growth QTL has previously been found in an intercross between White Leghorn layers (WL) and their main wild ancestor, the red junglefowl (RJF). This QTL has also been found to influence explorative and social behaviours. This thesis aims to characterize this QTL further with respect to social and emotional behaviours, and tries to clarify whether pleiotropy or linkage is responsible for the many observed effects. This is done using behavioural phenotyping, genetic marker genotyping, QTL- and gene expression analysis of an intercross line between RJF and WL, and to some extent of the parental RJF and WL lines themselves. The results show that domestication in these chickens has led to increased social tolerance to unfamiliar conspecifics and a tendency to a decrease in the propensity of chickens to explore the environment, and that these effects are partly explained by the previously described growth QTL. The results also indicate that close linkage of genes, rather than pleiotropy, may be responsible for the multiple effect of the QTL, as different traits to some extent seem to be influenced by different areas within the larger QTL region. This information, in combination with that of other studies and with existing and upcoming genetic research techniques, may be used in the design of future breeding programs that take animal behaviour and welfare as well as production traits into account. Findings like these may also be of use in directing research in human psychiatric genetics.
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| 24. |
- Wiren, Anders, et al.
(författare)
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Domestication-related genetic effects on social behavior in chickens - effects of genotype at a major growth quantitative trait locus
- 2009
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Ingår i: Poultry Science. - : Elsevier BV. - 0032-5791 .- 1525-3171. ; 88:6, s. 1162-1166
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Tidskriftsartikel (refereegranskat)abstract
- Domestication is an evolutionary process in which animals become adapted to a life in close proximity to humans. There are typically specific selection pressures associated with this, including living in larger social groups than their wild ancestors. We hypothesized that the genotype at a major growth QTL could affect aspects of social behavior in chickens as well. We performed social behavior tests in red junglefowl (RJF) and White Leghorn (WL) chickens and in chickens from a selected advanced intercross line (SAIL) between RJF and WL, selected for different genotypes at a microsatellite marker locus within the QTL region. Four-week-old pure WL inspected strangers significantly more than pure RJF. Male 4-wk-old SAIL birds, homozygous for the WL allele at the marker locus, differed from those with RJF alleles in a similar way as the pure WL differed from RJF. Furthermore, 155- to 170-d-old male SAIL birds homozygous for the WL allele at the marker locus were less aggressive to unfamiliar conspecifics in a dominance test. The results suggest that domestication has caused changes in social behavior, which, in males, may partly depend on variations in the genotype at the growth QTL where the avian homolog of the arginine vasopressin receptor 1a (AVPR1a) is located. This gene is therefore one of several putative candidate genes for future research.
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| 25. |
- Wirén, Anders, et al.
(författare)
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Domestication-related variation in social preferences in chickens is affected by genotype on a growth QTL
- 2013
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Ingår i: Genes, Brain and Behavior. - : Blackwell Publishing. - 1601-1848 .- 1601-183X. ; 12:3, s. 330-337
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Tidskriftsartikel (refereegranskat)abstract
- A growth-related QTL on chicken chromosome 1 has previously been shown to influence domestication behaviour in chickens. In this study, we used Red Junglefowl (RJF) and White Leghorn (WL) as well as the intercross between them to investigate whether stress affects the way birds allocate their time between familiar and unfamiliar conspecifics in a social preference test (‘social support seeking’), and how this is related to genotype at specific loci within the growth QTL. Red Junglefowl males spent more time with unfamiliar chickens before the stressful event compared to the other birds, whereas all birds except WL males tended to spend less time with unfamiliar ones after stress. A significant QTL locus was found to influence both social preference under undisturbed circumstances and social support seeking. The WL allele at this QTL was associated not only with a preference for unfamiliar individuals but also with a shift towards familiar ones in response to stress (social support seeking). A second, suggestive QTL also affected social support seeking, but in the opposite direction; the WL allele was associated with increased time spent with unfamiliar individuals. The region contains several possible candidate genes, and gene expression analysis of a number of them showed differential expression between RJF and WL of AVPR2 (receptor for vasotocin), and possibly AVPR1a (another vasotocin receptor) and NRCAM (involved in neural development) in the lower frontal lobes of the brains of RJF and WL animals. These three genes continue to be interesting candidates for the observed behavioural effects.
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| 26. |
- Wirén, Anders, et al.
(författare)
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Effects of a Chicken Growth QTL on Behaviour are due to Linkage rather than Pleiotropy
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- earlier studies, we have found pleiotropic effects of a growth QTL in chickens on behavioural traits that have changed as a result of domestication. In this study we performed a) a refined analysis of the QTL in an advanced intercross line between Red Junglefowl (RJF) and White Leghorn layers (WL) to investigate if different behavioural and physiological traits are associated with different regions of the QTL, and b) brain gene expression analysis (using qRT-PCR) in RJF and WL, comparing the expression between breeds of a number of genes within the growth QTL that may be considered candidates for affecting behavioural traits. The refined QTL analysis was performed on 62 birds from a selected line corresponding to the F7 generation of an RJF×WL intercross (SAIL). The gene expression analysis was performed on 12 RJF and 10 WL birds. In addition to recording of weight data, the SAIL birds were exposed to a behavioural test measuring aspects of sociality and emotionality. The QTL analysis found a significant association between body weight at 8 days of age and a 1.7 MB region in the QTL, and a suggestive association between emotionality related behaviours and a different part, 7.5 MB large, of the QTL. The gene expression analysis showed differential expression of AVPR2 (receptor for vasotocin), possibly AVPR1a (another vasotocin receptor) and NRCAM (involved in neural development) in the lower frontal lobes of the brains of RJF and WL birds. It therefore seems that linkage of several different genes affecting different traits, rather than pleiotropy of one or a few, may explain the many effects of this QTL, and that AVPR2, AVPR1a and NRCAM cannot be discarded as candidate genes for the observed effects.
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| 27. |
- Wirén, Anders, et al.
(författare)
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Social preference and support seeking in chickens is related to genotype on a growth QTL
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- A growth related QTL on chicken chromosome 1 has previously been shown to influence both emotionality and social behaviour in an intercross line between Red Junglefowl (RJF, ancestor of all domestic chicken breeds) and the domesticated White Leghorn layer (WL). Social support from a familiar animal has been shown to attenuate stress response in other species. In this study we therefore used the RJF×WL intercross line to investigate whether stress in the form of physical restraint affects the way birds allocate their time between familiar and unfamiliar conspecifics in a social preference test. A refined QTL study was performed, focussing on the region of the previously reported growth QTL to find possible loci affecting traits related to social preference and social support. A significant QTL was found to influence both social preference under undisturbed circumstances and social support seeking in response to stress. A WL allele at this QTL was associated with a preference for unfamiliar individuals but also with a shift towards familiar ones in response to stress. A second, suggestive, QTL also affected social support seeking, but in the opposite direction; a WL allele was associated with seeking social support from unfamiliar individuals. It is difficult to speculate on causative genes, but it is worth noting that AVPR1a (known for effects on social behaviour), AVPR2, NRCAM (related to autism) and GRIP1 (Glutamate Receptor Interacting Protein) are located this chromosomal area.
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| 28. |
- Wirén, Sara, 1981-, et al.
(författare)
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Androgens and prostate cancer risk : a prospective study
- 2007
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Ingår i: The Prostate. - : John Wiley & Sons. - 0270-4137 .- 1097-0045. ; 67:11, s. 1230-1237
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Tidskriftsartikel (refereegranskat)abstract
- Background: Androgens have been implicated in prostate tumorigenesis, but prospective studies have overall reported no association between circulating levels of androgens and risk of prostate cancer. However, some recent studies have shown that a high level of testosterone increase the risk of non-aggressive tumors but is associated with a decreased risk of aggressive tumors.Methods: We prospectively measured plasma levels of total testosterone, androstanediol glucuronide (A-diol-g) and sex hormone binding globuline (SHBG) and calculated estimated levels of free testosterone, in a nested case-control study of 392 cases and 392 matched controls.Results: None of the studied hormones were significantly associated with prostate cancer risk in the full study group or in subgroups according to tumor aggressiveness. Odds ratios in the full study group, for top versus bottom quartile, was for total testosterone 1.25 (95% CI = 0.79–2.00; Ptrend = 0.51); free testosterone, 1.31 (95% CI = 0.82–2.07; Ptrend = 0.35); A-diol-g, 0.88 (95% CI = 0.59–1.33; Ptrend = 0.77); and for SHBG, 1.01 (95% CI = 0.64–1.58; Ptrend = 0.94).Conclusions: We found no significant associations between androgen levels and risk of prostate cancer in this population-based, non-screened cohort.
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| 29. |
- Wirén, Sara, et al.
(författare)
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Pooled cohort study on height and risk of cancer and cancer death
- 2014
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Ingår i: Cancer Causes and Control. - : Springer Berlin/Heidelberg. - 0957-5243 .- 1573-7225. ; 25:2, s. 151-159
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To assess the association between height and risk of cancer and cancer death.METHODS: The metabolic syndrome and cancer project is a prospective pooled cohort study of 585,928 participants from seven cohorts in Austria, Norway, and Sweden. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for cancer incidence and death were estimated in height categories and per 5-cm increment for each cancer site using Cox proportional hazards model.RESULTS: During a mean follow-up of 12.7 years (SD = 7.2), 38,862 participants were diagnosed with cancer and 13,547 participants died of cancer. Increased height (per 5-cm increment) was associated with an increased overall cancer risk in women, HR 1.07 (95 % CI 1.06-1.09), and in men, HR 1.04 (95 % CI 1.03-1.06). The highest HR was seen for malignant melanoma in women, HR 1.17 (95 % CI 1.11-1.24), and in men HR 1.12 (95 % CI 1.08-1.19). Height was also associated with increased risk of cancer death in women, HR 1.03 (95 % CI 1.01-1.16), and in men, HR 1.03 (95 % CI 1.01-1.05). The highest HR was observed for breast cancer death in postmenopausal women (>60 years), HR 1.10 (95 % CI 1.00-1.21), and death from renal cell carcinoma in men, HR 1.18 (95 % CI 1.07-1.30). All these associations were independent of body mass index.CONCLUSION: Height was associated with risk of cancer and cancer death indicating that factors related to height such as hormonal and genetic factors stimulate both cancer development and progression.
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