| 1. |
- Fages, A., et al.
(författare)
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Tracking Five Millennia of Horse Management with Extensive Ancient Genome Time Series
- 2019
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Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 177:6
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Tidskriftsartikel (refereegranskat)abstract
- Horse domestication revolutionized warfare and accelerated travel, trade, and the geographic expansion of languages. Here, we present the largest DNA time series for a non-human organism to date, including genome-scale data from 149 ancient animals and 129 ancient genomes (>= 1-fold coverage), 87 of which are new. This extensive dataset allows us to assess the modem legacy of past equestrian civilisations. We find that two extinct horse lineages existed during early domestication, one at the far western (Iberia) and the other at the far eastern range (Siberia) of Eurasia. None of these contributed significantly to modern diversity. We show that the influence of Persian-related horse lineages increased following the Islamic conquests in Europe and Asia. Multiple alleles associated with elite-racing, including at the MSTN "speed gene," only rose in popularity within the last millennium. Finally, the development of modem breeding impacted genetic diversity more dramatically than the previous millennia of human management.
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| 2. |
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| 3. |
- Ameen, Carly, et al.
(författare)
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Specialized sledge dogs accompanied Inuit dispersal across the North American Arctic
- 2019
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Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 286:1916
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Tidskriftsartikel (refereegranskat)abstract
- Domestic dogs have been central to life in the North American Arctic for millennia. The ancestors of the Inuit were the first to introduce the widespread usage of dog sledge transportation technology to the Americas, but whether the Inuit adopted local Palaeo-Inuit dogs or introduced a new dog population to the region remains unknown. To test these hypotheses, we generated mitochondrial DNA and geometric morphometric data of skull and dental elements from a total of 922 North American Arctic dogs and wolves spanning over 4500 years. Our analyses revealed that dogs from Inuit sites dating from 2000 BP possess morphological and genetic signatures that distinguish them from earlier Palaeo-Inuit dogs, and identified a novel mitochondrial clade in eastern Siberia and Alaska. The genetic legacy of these Inuit dogs survives today in modern Arctic sledge dogs despite phenotypic differences between archaeological and modern Arctic dogs. Together, our data reveal that Inuit dogs derive from a secondary pre-contact migration of dogs distinct from Palaeo-Inuit dogs, and probably aided the Inuit expansion across the North American Arctic beginning around 1000 BP.
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| 5. |
- Bjornebo, L, et al.
(författare)
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Association of 5α-Reductase Inhibitors With Prostate Cancer Mortality
- 2022
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Ingår i: JAMA oncology. - : American Medical Association (AMA). - 2374-2445 .- 2374-2437. ; 8:87, s. 1019-1026
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Tidskriftsartikel (refereegranskat)abstract
- There is evidence that 5α-reductase inhibitors (5-ARIs), a standard treatment of benign prostate hyperplasia, are associated with a decrease in the incidence of prostate cancer (PCa). However, studies to date have had conflicting results regarding the association with prostate cancer mortality (PCM).ObjectiveTo evaluate the association of treatment with 5-ARIs with PCM in men without a prior diagnosis of PCa.Design, Setting, and ParticipantsThis population-based cohort study was conducted in Stockholm, Sweden, between January 1, 2007, and December 31, 2018, and included 429 977 men with a prostate-specific antigen (PSA) test within the study period. Study entry was set to 1 year after the first PSA test. Data were analyzed from September 2021 to December 2021.ExposuresAfter their initial PSA test, men with 2 or more newly dispensed prescriptions of 5-ARI, finasteride, or dutasteride were considered 5-ARI users (n = 26 190).Main Outcomes and MeasuresPrimary outcome was PCM. Cox proportional hazards regression models were used to calculate multivariable-adjusted hazard ratios (HRs) and 95% CIs for all-cause mortality and PCM.ResultsThe study cohort included 349 152 men. The median (IQR) age for those with 2 or more filled prescriptions of 5-ARI was 66 (61-73) years and 57 (50-64) years for those without. The median follow-up time was 8.2 (IQR, 4.9-10) years with 2 257 619 person-years for the unexposed group and 124 008 person-years for the exposed group. The median exposure to treatment with 5-ARI was 4.5 (IQR, 2.1-7.4) years. During follow-up, 35 767 men (8.3%) died, with 852 deaths associated with PCa. The adjusted multivariable survival analysis showed a lower risk of PCM in the 5-ARI group with longer exposure times (0.1-2.0 years: adjusted HR, 0.89; 95% CI, 0.64-1.25; >8 years: adjusted HR, 0.44; 95% CI, 0.27-0.74). No statistically significant differences were seen in all-cause mortality between the exposed and unexposed group. Men treated with 5-ARIs underwent more PSA tests and biopsies per year than the unexposed group (median of 0.63 vs 0.33 and 0.22 vs 0.12, respectively).Conclusions and RelevanceThe results of this cohort study suggest that there was no association between treatment with 5-ARI and increased PCM in a large population-based cohort of men without a previous PCa diagnosis. Additionally, a time-dependent association was seen with decreased risk of PCM with longer 5-ARI treatment. Further research is needed to determine whether the differences are because of intrinsic drug effects or PCa testing differences.
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| 10. |
- Helgadottir, Anna, et al.
(författare)
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The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:2, s. 217-224
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Tidskriftsartikel (refereegranskat)abstract
- Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD)(1-4) and type 2 diabetes (T2D)(5-7), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.
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| 18. |
- Palsdottir, T, et al.
(författare)
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The impact of different prostate-specific antigen (PSA) testing intervals on Gleason score at diagnosis and the risk of experiencing false-positive biopsy recommendations: a population-based cohort study
- 2019
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 9:3, s. e027958-
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Tidskriftsartikel (refereegranskat)abstract
- Given a man’s current prostate- specific antigen (PSA) level, age and family history of prostate cancer, what are the benefits (decreased risk of higher Gleason score [GS] cancer at diagnosis) and harms (increased risk of false-positive biopsy recommendation) of waiting 1, 2, 3, 4 or 5–8 years until the next PSA test?DesignProspective cohort.SettingAll PSA tested men in Stockholm, Sweden, between 2003 and 2015.ParticipantsMen aged 50–74 years with at least two PSA tests between 2003 and 2015 (n=174 636).Main outcome measuresLog-binomial regression to calculate the risk ratio (RR) of GS ≥7 and GS 6 versus benign outcome at prostate biopsy and 12-year cumulative probability of experiencing a false-positive biopsy by testing interval, age, PSA level and first-degree family history.ResultsMen with PSA ≤1 ng/mL had low risk of GS ≥7 prostate cancer irrespective of testing interval; <3% had a PSA >3 at the next testing occasion, and of the 663 men biopsied after the next PSA test only 32 (5%) had GS ≥7 cancer. Men with PSA >1 ng/mL had increased risk of being diagnosed with GS ≥7 prostate cancer when screened with longer than annual intervals (RRs ranged from 1.4 to 3.2 depending on PSA level and testing interval). The results were consistent across age groups and family history status. This benefit needs to be balanced against the increased risk for false-positive biopsy recommendation with shorter testing intervals (twofold for annual vs biennial and threefold for annual vs triennial).ConclusionsMen aged 50–74 years with PSA ≤1 ng/mL can wait 3–4 years before having a new PSA test. For men with PSA >1 ng/mL, we observed an increased risk of being diagnosed with GS ≥7 prostate cancer with longer than annual testing intervals. This benefit needs to be balanced against the markedly increased risks for false-positive biopsy recommendations with shorter testing intervals recommendations.
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| 21. |
- Hoffmann, Jenny M, et al.
(författare)
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BMP4 gene therapy enhances insulin sensitivity but not adipose tissue browning in obese mice
- 2020
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Ingår i: Molecular Metabolism. - : Elsevier BV. - 2212-8778. ; 32, s. 15-26
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Bone morphogenetic protein 4 (BMP4) adeno-associated viral vectors of serotype 8 (AAV8) gene therapy targeting the liver prevents the development of obesity in initially lean mice by browning the large subcutaneous white adipose tissue (WAT) and enhancing energy expenditure. Here, we examine whether this approach could also reduce established obesity. Methods: Dietary-induced obese C57BL6/N mice received AAV8 BMP4 gene therapy at 17-18 weeks of age. They were kept on a high-fat diet and phenotypically characterized for an additional 10-12 weeks. Following termination, the mice underwent additional characterization in vitro. Results: Surprisingly, we observed no effect on body weight, browning of WAT, or energy expenditure in these obese mice, but whole-body insulin sensitivity and glucose tolerance were robustly improved. Insulin signaling and insulin-stimulated glucose uptake were increased in both adipose cells and skeletal muscle. BMP4 also decreased hepatic glucose production and reduced gluconeogenic enzymes in the liver, but not in the kidney, in addition to enhancing insulin action in the liver. Conclusions: Our findings show that BMP4 prevents, but does not reverse, established obesity in adult mice, while it improves insulin sensitivity independent of weight reduction. The BMP antagonist Noggin was increased in WAT in obesity, which may account for the lack of browning. (C) 2019 The Author(s). Published by Elsevier GmbH.
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| 23. |
- Kristjansson, S., et al.
(författare)
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Respiratory syncytial virus and other respiratory viruses during the first 3 months of life promote a local TH2-like response
- 2005
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Ingår i: J Allergy Clin Immunol. - : Elsevier BV. - 0091-6749. ; 116:4, s. 805-11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Respiratory syncytial virus (RSV) infections during infancy are considered to be a risk factor for developing asthma and possibly allergic sensitization. OBJECTIVE: The aim of this study was to investigate the cytokines, chemokines, and eosinophil cationic protein in the nasopharyngeal secretions of infants < or = 7 months of age with RSV infections or other respiratory viral infections and healthy infants as controls. Groups were also analyzed according to age, < or = 3 months and >3 months, and the levels were compared within and between groups. RESULTS: Thirty-nine infants with RSV, 9 with influenza or parainfluenza virus infections and 50 controls with no history of infections, were enrolled in the study. The RSV-infected infants had significantly higher levels of IL-4; macrophage inflammatory protein 1beta, a chemoattractant for T cells; and eosinophil cationic protein in nasopharyngeal secretions compared with the control group. The levels of the TH2 cytokine IL-4 were significantly higher in RSV-infected infants < or = months of age compared with RSV-infected infants >3 months of age. In infants < or = 3 months of age, infections with influenza or parainfluenza virus caused TH2-like responses similar to those produced by RSV. CONCLUSION: Infections with RSV as well as with influenza and parainfluenza virus during early infancy preferentially promote a TH2-like response in the nose with local production of IL-4, IL-5, and macrophage inflammatory protein 1beta and infiltration and activation of eosinophils.
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| 24. |
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| 25. |
- Palsdottir, A, et al.
(författare)
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Study of restriction fragment length polymorphism in the cystatin C gene of elderly patients with dementia and aged Down's syndrome patients
- 1989
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Ingår i: Progress in Clinical and Biological Research. - 0361-7742. ; 317, s. 235-239
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Tidskriftsartikel (refereegranskat)abstract
- Using a full length cystatin C cDNA probe and the Alu I restriction enzyme a total of 33 patients with senile dementia, Alzheimer type and 31 Down's syndrome patients have been investigated for the presence of the 630 bp Alu I restriction fragment length polymorphism in the cystatin C gene detected in Icelandic patients with hereditary cystatin C amyloid angiopathy. Results showed that all the patients had normal cystatin C fragment length of 600 bp.
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| 29. |
- Palsdottir, Vilborg, 1979, et al.
(författare)
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Interactions Between the Gravitostat and the Fibroblast Growth Factor System for the Regulation of Body Weight
- 2019
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 160:5, s. 1057-1064
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Tidskriftsartikel (refereegranskat)abstract
- Both fibroblast growth factors (FGFs), by binding to FGF receptors (FGFRs), and activation of the gravitostat, by artificial loading, decrease the body weight (BW). Previous studies demonstrate that both the FGF system and loading have the capacity to regulate BW independently of leptin. The aim of the current study was to determine the possible interactions between the effect of increased loading and the FGF system for the regulation of BW. We observed that the BW-reducing effect of increased loading was abolished in mice treated with a monoclonal antibody directed against FGFR1c, suggesting interactions between the two systems. As serum levels of endocrine FGF21 and hepatic FGF21 mRNA were increased in the loaded mice compared with the control mice, we first evaluated the loading response in FGF21 over expressing mice with constant high FGF21 levels. Leptin treatment, but not increased loading, decreased the BW in the FGF21-overexpressing mice, demonstrating that specifically the loading effect is attenuated in the presence of high activity in the FGF system. However, as FGF21 knockout mice displayed a normal loading response on BW, FGF21 is neither mediating nor essential for the loading response. In conclusion, the BW-reducing effect of increased loading but not of leptin treatment is blocked by high activity in the FGF system. We propose that both the gravitostat and the FGF system regulate BW independently of leptin and that pharmacologically enhanced activity in the FGF system reduces the sensitivity of the grayitostat.
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| 30. |
- Salvo, Gloria, et al.
(författare)
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Open vs minimally invasive radical trachelectomy in early-stage cervical cancer : International Radical Trachelectomy Assessment Study
- 2022
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 226:1, s. 1-97
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Tidskriftsartikel (refereegranskat)abstract
- Background: Minimally invasive radical trachelectomy has emerged as an alternative to open radical hysterectomy for patients with early-stage cervical cancer desiring future fertility. Recent data suggest worse oncologic outcomes after minimally invasive radical hysterectomy than after open radical hysterectomy in stage I cervical cancer. Objective: We aimed to compare 4.5-year disease-free survival after open vs minimally invasive radical trachelectomy. Study Design: This was a collaborative, international retrospective study (International Radical Trachelectomy Assessment Study) of patients treated during 2005–2017 at 18 centers in 12 countries. Eligible patients had squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma; had a preoperative tumor size of ≤2 cm; and underwent open or minimally invasive (robotic or laparoscopic) radical trachelectomy with nodal assessment (pelvic lymphadenectomy and/or sentinel lymph node biopsy). The exclusion criteria included neoadjuvant chemotherapy or preoperative pelvic radiotherapy, previous lymphadenectomy or pelvic retroperitoneal surgery, pregnancy, stage IA1 disease with lymphovascular space invasion, aborted trachelectomy (conversion to radical hysterectomy), or vaginal approach. Surgical approach, indication, and adjuvant therapy regimen were at the discretion of the treating institution. A total of 715 patients were entered into the study database. However, 69 patients were excluded, leaving 646 in the analysis. Endpoints were the 4.5-year disease-free survival rate (primary), 4.5-year overall survival rate (secondary), and recurrence rate (secondary). Kaplan-Meier methods were used to estimate disease-free survival and overall survival. A post hoc weighted analysis was performed, comparing the recurrence rates between surgical approaches, with open surgery being considered as standard and minimally invasive surgery as experimental. Results: Of 646 patients, 358 underwent open surgery, and 288 underwent minimally invasive surgery. The median (range) patient age was 32 (20–42) years for open surgery vs 31 (18–45) years for minimally invasive surgery (P=.11). Median (range) pathologic tumor size was 15 (0–31) mm for open surgery and 12 (0.8–40) mm for minimally invasive surgery (P=.33). The rates of pelvic nodal involvement were 5.3% (19 of 358 patients) for open surgery and 4.9% (14 of 288 patients) for minimally invasive surgery (P=.81). Median (range) follow-up time was 5.5 (0.20–16.70) years for open surgery and 3.1 years (0.02–11.10) years for minimally invasive surgery (P<.001). At 4.5 years, 17 of 358 patients (4.7%) with open surgery and 18 of 288 patients (6.2%) with minimally invasive surgery had recurrence (P=.40). The 4.5-year disease-free survival rates were 94.3% (95% confidence interval, 91.6–97.0) for open surgery and 91.5% (95% confidence interval, 87.6–95.6) for minimally invasive surgery (log-rank P=.37). Post hoc propensity score analysis of recurrence risk showed no difference between surgical approaches (P=.42). At 4.5 years, there were 6 disease-related deaths (open surgery, 3; minimally invasive surgery, 3) (log-rank P=.49). The 4.5-year overall survival rates were 99.2% (95% confidence interval, 97.6–99.7) for open surgery and 99.0% (95% confidence interval, 79.0–99.8) for minimally invasive surgery. Conclusion: The 4.5-year disease-free survival rates did not differ between open radical trachelectomy and minimally invasive radical trachelectomy. However, recurrence rates in each group were low. Ongoing prospective studies of conservative management of early-stage cervical cancer may help guide future management.
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