| 1. |
- Culverhouse, R. C., et al.
(författare)
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Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression
- 2018
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23:1, s. 133-142
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Tidskriftsartikel (refereegranskat)abstract
- The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations.
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| 2. |
- Goyal, S. D., et al.
(författare)
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Allogeneic hematopoietic cell transplant for AML : no impact of pre-transplant extramedullary disease on outcome
- 2015
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 50:8, s. 1057-1062
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Tidskriftsartikel (refereegranskat)abstract
- The impact of extramedullary disease (EMD) in AML on the outcomes of allogeneic hematopoietic cell transplantation (alloHCT) is unknown. Using data from the Center for International Blood and Marrow Transplant Research, we compared the outcomes of patients who had EMD of AML at any time before transplant, with a cohort of AML patients without EMD. We reviewed data from 9797 AML patients including 814 with EMD from 310 reporting centers and 44 different countries, who underwent alloHCT between and 1995 and 2010. The primary outcome was overall survival (OS) after alloHCT. Secondary outcomes included leukemia-free survival (LFS), relapse rate and treatment-related mortality (TRM). In a multivariate analysis, the presence of EMD did not affect either OS (hazard ratio 1.00, 95% confidence interval (Cl) 0.91-1.09), LFS (0.98, 0.89-1.09), TRM (relative risk 0.92, 95% CI 0.80-1.16, P=0.23) or relapse (relative risk= 1.03, 95% CI, 0.92-1.16; P=0.62). Furthermore, the outcome of patients with EMD was not influenced by the location, timing of EMD, or intensity of conditioning regimen. The presence of EMD in AML does not affect transplant outcomes and should not be viewed as an independent adverse prognostic feature.
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| 3. |
- H.L., Olsson
(författare)
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With increasing age at tumor diagnosis in families with cancer, cancer is limited to fewer organs
- 2016
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Ingår i: Cancer Research. - 1538-7445. ; 76:14 Suppl
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Konferensbidrag (refereegranskat)abstract
- Hereditary cancer that has monogenic inheritance affects every tenth patient, on average, who is diagnosed with cancer, and it has been suggested based on twin studies, that approximately 30% of all cancer patients have a genetic predisposition to developing cancer. The author posited that familial syndromes become more organ specific with increasing age at tumour presentation to the point that very late in life, only a few organs are affected by tumours disease. The reason for this could be that the tumour originates from a more differentiated, organ-specific progenitor/stem cell later in life, while the progenitor/stem cell might be involved in organogenesis in different organs earlier in life. Examples are given for skin cancer and breast cancer. Summary: Patients with familial cancer who present with cancer at an older age at tumour presentation have a more organ restricted disease. This could be because the tumor has a more differentiated progenitor/stem cell origin. Examples are given for families with breast cancer, melanoma, and non-melanoma skin cancer.
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| 4. |
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| 5. |
- Rollings, N., et al.
(författare)
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Age-related sex differences in body condition and telomere dynamics of red-sided garter snakes
- 2017
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Ingår i: Proceedings of the Royal Society B-Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 284:1852
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Tidskriftsartikel (refereegranskat)abstract
- Life-history strategies vary dramatically between the sexes, which may drive divergence in sex-specific senescence and mortality rates. Telomeres are tandem nucleotide repeats that protect the ends of chromosomes from erosion during cell division. Telomeres have been implicated in senescence and mortality because they tend to shorten with stress, growth and age. We investigated age-specific telomere length in female and male red-sided garter snakes, Thamnophis sirtalis parietalis. We hypothesized that age-specific telomere length would differ between males and females given their divergent reproductive strategies. Male garter snakes emerge from hibernation with high levels of corticosterone, which facilitates energy mobilization to fuel mate-searching, courtship and mating behaviours during a two to four week aphagous breeding period at the den site. Conversely, females remain at the dens for only about 4 days and seem to invest more energy in growth and cellular maintenance, as they usually reproduce biennially. As male investment in reproduction involves a yearly bout of physiologically stressful activities, while females prioritize self-maintenance, we predicted male snakes would experience more age-specific telomere loss than females. We investigated this prediction using skeletochronology to determine the ages of individuals and qPCR to determine telomere length in a cross-sectional study. For both sexes, telomere length was positively related to body condition. Telomere length decreased with age in male garter snakes, but remained stable in female snakes. There was no correlation between telomere length and growth in either sex, suggesting that our results are a consequence of divergent selection on life histories of males and females. Different selection on the sexes may be the physiological consequence of the sexual dimorphism and mating system dynamics displayed by this species.
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| 6. |
- Rollings, N., et al.
(författare)
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Sperm telomere length correlates with blood telomeres and body size in red-sided garter snakes, Thamnophis sirtalis parietalis
- 2020
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Ingår i: Journal of Zoology. - : Wiley. - 0952-8369 .- 1469-7998. ; 312:1, s. 21-31
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Tidskriftsartikel (refereegranskat)abstract
- Telomeres, tandem repeats of TTAGGG at the ends of chromosomes, are highly dynamic structures that shorten in response to a variety of factors, including organismal stress and tissue-specific growth rates. Cell turnover rates are frequently linked to their functions, resource availability and telomere dynamics. Using male red-sided garter snakes, Thamnophis sirtalis parietalis, as a model, we investigated the relationship between telomere length in sperm cells, blood cells telomere length and a growth proxy (age-adjusted body length and mass). This relationship is interesting because snakes exhibit indeterminate growth and because these garter snakes have a dissociated reproductive cycle where spermatogenesis occurs months prior to the mating season. In this study, we determined sperm telomere length (STL) and male age using qPCR and skeletochronology, respectively. Sperm telomere length correlated positively with snout-vent length (SVL) and with age-adjusted SVL as a proxy for growth rate (residuals of size against age regression, hereafter growth), but not with age. Although an individual's STL is correlated with blood telomere length (BTL), sperm telomeres are 60% longer than blood telomeres. In previous work, we have shown that BTL is shorter in older males and unrelated to SVL or any growth rate proxies. We hypothesized that STL is related to growth and SVL because growth and sperm production both occur during summer when resources are most abundant and stress lowest. This study is the first to compare telomere dynamics between cell types in a snake and supports growing evidence that telomere dynamics may be highly tissue-specific and driven by the life-history strategy of an organism.
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