| 1. |
- Jiang, X., et al.
(författare)
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Shared heritability and functional enrichment across six solid cancers
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
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| 2. |
- Needham, E. J., et al.
(författare)
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Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses
- 2022
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 145:11, s. 4097-4107
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19 is associated with neurological complications including stroke, delirium and encephalitis. Furthermore, a post-viral syndrome dominated by neuropsychiatric symptoms is common, and is seemingly unrelated to COVID-19 severity. The true frequency and underlying mechanisms of neurological injury are unknown, but exaggerated host inflammatory responses appear to be a key driver of COVID-19 severity. We investigated the dynamics of, and relationship between, serum markers of brain injury [neurofilament light (NfL), glial fibrillary acidic protein (GFAP) and total tau] and markers of dysregulated host response (autoantibody production and cytokine profiles) in 175 patients admitted with COVID-19 and 45 patients with influenza. During hospitalization, sera from patients with COVID-19 demonstrated elevations of NfL and GFAP in a severity-dependent manner, with evidence of ongoing active brain injury at follow-up 4 months later. These biomarkers were associated with elevations of pro-inflammatory cytokines and the presence of autoantibodies to a large number of different antigens. Autoantibodies were commonly seen against lung surfactant proteins but also brain proteins such as myelin associated glycoprotein. Commensurate findings were seen in the influenza cohort. A distinct process characterized by elevation of serum total tau was seen in patients at follow-up, which appeared to be independent of initial disease severity and was not associated with dysregulated immune responses unlike NfL and GFAP. These results demonstrate that brain injury is a common consequence of both COVID-19 and influenza, and is therefore likely to be a feature of severe viral infection more broadly. The brain injury occurs in the context of dysregulation of both innate and adaptive immune responses, with no single pathogenic mechanism clearly responsible. Needham et al. reveal elevations in blood biomarkers of brain injury in patients hospitalised with COVID-19. The changes, which were severity-dependent, were associated with dysregulated immune responses including increases in pro-inflammatory cytokines and autoantibodies. Ongoing active brain injury could still be seen months after infection.
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| 3. |
- Carlomagno, F, et al.
(författare)
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Comparison of DNA repair protein expression and activities between human fibroblast cell lines with different radiosensitivities.
- 2000
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Ingår i: International journal of cancer. Journal international du cancer. - 0020-7136. ; 85:6, s. 845-9
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Tidskriftsartikel (refereegranskat)abstract
- In order to investigate the molecular basis of variation in response to ionising radiation (IR) in radiotherapy patients, we have studied the expression of several genes involved in DNA double-strand break repair pathways in fibroblast cell lines. Ten lines were established from skin biopsies of cancer patients with different normal-tissue reactions to IR, and 3 from a control individual. For all 10 test cell lines, the cellular radiosensitivity was also known. Using Western blots we measured, in non-irradiated cells, the basal expression levels of ATM, Rad1 and Hus1, involved in the control of cellular DNA damage checkpoints, together with DNA-PKcs, Ku70, Ku80; XRCC4, ligaseIV and Rad51, involved in radiation- induced DSB repair. We also analysed the in vitro enzymatic activities, under non-irradiated conditions, of the DNA-PK and XRCC4/ligaseIV complexes. The levels of expression of the different proteins were similar in all the cell lines, but the activities of the DNA-PK and XRCC4/ligaseIV complexes showed some differences. These differences did not correlate with either the normal tissue response of the patient in vivo or with cellular radiation sensitivity in vitro. The activity differences of these enzyme complexes, therefore, do not account for the variation of responses seen between patients.
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| 4. |
- Dunning, L. T., et al.
(författare)
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Ecological speciation in sympatric palms: 1. Gene expression, selection and pleiotropy
- 2016
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Ingår i: Journal of Evolutionary Biology. - : Wiley. - 1010-061X .- 1420-9101. ; 29:8, s. 1472-1487
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Tidskriftsartikel (refereegranskat)abstract
- Ecological speciation requires divergent selection, reproductive isolation and a genetic mechanism to link the two. We examined the role of gene expression and coding sequence evolution in this process using two species of Howea palms that have diverged sympatrically on Lord Howe Island, Australia. These palms are associated with distinct soil types and have displaced flowering times, representing an ideal candidate for ecological speciation. We generated large amounts of RNA-Seq data from multiple individuals and tissue types collected on the island from each of the two species. We found that differentially expressed loci as well as those with divergent coding sequences between Howea species were associated with known ecological and phenotypic differences, including response to salinity, drought, pH and flowering time. From these loci, we identified potential ecological speciation genes' and further validate their effect on flowering time by knocking out orthologous loci in a model plant species. Finally, we put forward six plausible ecological speciation loci, providing support for the hypothesis that pleiotropy could help to overcome the antagonism between selection and recombination during speciation with gene flow.
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| 5. |
- Hipperson, H., et al.
(författare)
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Ecological speciation in sympatric palms: 2. Pre- and post-zygotic isolation
- 2016
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Ingår i: Journal of Evolutionary Biology. - : Wiley. - 1010-061X .- 1420-9101. ; 29:11, s. 2143-2156
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated reproductive isolation in two species of palms (Howea) that have evolved sympatrically on Lord Howe Island (LHI, Australia). We estimated the strength of some pre- and post-zygotic mechanisms in maintaining current species boundaries. We found that flowering time displacement between species is consistent across in and ex situ common gardens and is thus partly genetically determined. On LHI, pre-zygotic isolation due solely to flowering displacement was 97% for Howea belmoreana and 80% for H. forsteriana; this asymmetry results from H. forsteriana flowering earlier than H. belmoreana and being protandrous. As expected, only a few hybrids (here confirmed by genotyping) at both juvenile and adult stages could be detected in two sites on LHI, in which the two species grow intermingled (the Far Flats) or adjacently (Transit Hill). Yet, the distribution of hybrids was different between sites. At Transit Hill, we found no hybrid adult trees, but 13.5% of younger palms examined there were of late hybrid classes. In contrast, we found four hybrid adult trees, mostly of late hybrid classes, and only one juvenile F1 hybrid in the Far Flats. This pattern indicates that selection acts against hybrids between the juvenile and adult stages. An in situ reciprocal seed transplant between volcanic and calcareous soils also shows that early fitness components (up to 36 months) were affected by species and soil. These results are indicative of divergent selection in reproductive isolation, although it does not solely explain the current distribution of the two species on LHI.
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| 6. |
- Isendahl, Christian, 1965, et al.
(författare)
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Growth and Decline in Classic Maya Puuc Political Economies
- 2014
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Ingår i: The Resilience and Vulnerability of Ancient Landscapes: Transforming Maya Archaeology through IHOPE. Archaeological Paper of the American Anthropological Association, Vol. 24, edited by Arlen F. Chase and Vernon L. Scarborough. - Arlington : American Anthropological Association. ; , s. 43-55
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Bokkapitel (refereegranskat)
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| 7. |
- Isendahl, Christian, 1965, et al.
(författare)
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Growth and Decline in Classic Maya Puuc Political Economies
- 2014
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Ingår i: ARCHEOLOGICAL PAPERS OF THE AMERICAN ANTHROPOLOGICAL ASSOCIATION. - : Wiley. - 1551-823X. ; 24, s. 43-55
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Tidskriftsartikel (refereegranskat)abstract
- The Classic period Puuc region presents Maya archaeologists with significant challenges. One challenge to interpretation lies in the fact that, despite a form of agro-urban settlement that proved highly resilient in the Maya Lowlands overall, Puuc cities flourished relatively briefly, beginning on a grand scale in the sixth century C.E. and with a halt in major building construction and depopulation in the tenth century C.E. This chapter focuses on analyzing how the Puuc economy depended on sustained economic growth and ultimately suffered its consequences for long-term agro-ecological sustainability. We suggest that an important clue to understanding urban collapse in the Puuc is found by looking at transitions in the net energy gain of the agricultural economy over the long-term. The boom-and-crash character of Puuc economic history follows a series of opportunities, challenges, and problem-solving with varying efficacy for long- and short-term sustainability and resilience. These factors include the highly fertile soils as the main resource; water scarcity as a limiting factor; effective water management as a key solution; and costly social complexity a driving force of agro-economic growth. The diminishing returns on energy invested were consequences of a dependency on economic growth as the supply of the primary resource decreased. The elite segments of polities were unable to adjust to decreasing returns, which led to economic decline and, eventually, organizational collapse. The boom-and-crash character of Puuc settlement suggests a political economy that had locked into dependency on constant growth and failed to adapt to diminishing returns. © 2014 by the American Anthropological Association.
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| 8. |
- Papadopulos, A. S. T., et al.
(författare)
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Ecological speciation in sympatric palms: 3. Genetic map reveals genomic islands underlying species divergence in Howea
- 2019
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Ingår i: Evolution. - : Wiley. - 0014-3820 .- 1558-5646. ; 73:9, s. 1986-1995
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Tidskriftsartikel (refereegranskat)abstract
- Although it is now widely accepted that speciation can occur in the face of continuous gene flow, with little or no spatial separation, the mechanisms and genomic architectures that permit such divergence are still debated. Here, we examined speciation in the face of gene flow in the Howea palms of Lord Howe Island, Australia. We built a genetic map using a novel method applicable to long-lived tree species, combining it with double digest restriction site–associated DNA sequencing of multiple individuals. Based upon various metrics, we detected 46 highly differentiated regions throughout the genome, four of which contained genes with functions that are particularly relevant to the speciation scenario for Howea, specifically salt and drought tolerance. © 2019 The Author(s). Evolution © 2019 The Society for the Study of Evolution.
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