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- Bonham, LW, et al.
(författare)
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Genetic variation across RNA metabolism and cell death gene networks is implicated in the semantic variant of primary progressive aphasia
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10854-
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Tidskriftsartikel (refereegranskat)abstract
- The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by neurodegeneration and progressive loss of semantic knowledge. Unlike many other forms of frontotemporal lobar degeneration (FTLD), svPPA has a highly consistent underlying pathology composed of TDP-43 (a regulator of RNA and DNA transcription metabolism). Previous genetic studies of svPPA are limited by small sample sizes and a paucity of common risk variants. Despite this, svPPA’s relatively homogenous clinicopathologic phenotype makes it an ideal investigative model to examine genetic processes that may drive neurodegenerative disease. In this study, we used GWAS metadata, tissue samples from pathologically confirmed frontotemporal lobar degeneration, and in silico techniques to identify and characterize protein interaction networks associated with svPPA risk. We identified 64 svPPA risk genes that interact at the protein level. The protein pathways represented in this svPPA gene network are critical regulators of RNA metabolism and cell death, such as SMAD proteins and NOTCH1. Many of the genes in this network are involved in TDP-43 metabolism. Contrary to the conventional notion that svPPA is a clinical syndrome with few genetic risk factors, our analyses show that svPPA risk is complex and polygenic in nature. Risk for svPPA is likely driven by multiple common variants in genes interacting with TDP-43, along with cell death,x` working in combination to promote neurodegeneration.
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- Rainsley, Eleanor, et al.
(författare)
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Pleistocene glacial history of the New Zealand subantarctic islands
- 2019
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 15:2, s. 423-448
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Tidskriftsartikel (refereegranskat)abstract
- The New Zealand subantarctic islands of Auckland and Campbell, situated between the subtropical front and the Antarctic Convergence in the Pacific sector of the Southern Ocean, provide valuable terrestrial records from a globally important climatic region. Whilst the islands show clear evidence of past glaciation, the timing and mechanisms behind Pleistocene environmental and climate changes remain uncertain. Here we present a multidisciplinary study of the islands-including marine and terrestrial geomorphological surveys, extensive analyses of sedimentary sequences, a comprehensive dating programme, and glacier flow line modelling-to investigate multiple phases of glaciation across the islands. We find evidence that the Auckland Islands hosted a small ice cap 384 000 +/- 26 000 years ago (384 +/- 26 ka), most likely during Marine Isotope Stage 10, a period when the subtropical front was reportedly north of its present-day latitude by several degrees, and consistent with hemispheric-wide glacial expansion. Flow line modelling constrained by field evidence suggests a more restricted glacial period prior to the LGM that formed substantial valley glaciers on the Campbell and Auckland Islands around 72-62 ka. Despite previous interpretations that suggest the maximum glacial extent occurred in the form of valley glaciation at the Last Glacial Maximum (LGM; similar to 21 ka), our combined approach suggests minimal LGM glaciation across the New Zealand subantarctic islands and that no glaciers were present during the Antarctic Cold Reversal (ACR; similar to 15-13 ka). Instead, modelling implies that despite a regional mean annual air temperature depression of similar to 5 degrees C during the LGM, a combination of high seasonality and low precipitation left the islands incapable of sustaining significant glaciation. We suggest that northwards expansion of winter sea ice during the LGM and subsequent ACR led to precipitation starvation across the middle to high latitudes of the Southern Ocean, resulting in restricted glaciation of the subantarctic islands.
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