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- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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- Kang, E. Y., et al.
(author)
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Refined cut-off for TP53 immunohistochemistry improves prediction of TP53 mutation status in ovarian mucinous tumors: implications for outcome analyses
- 2021
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In: Modern Pathology. - : Elsevier BV. - 0893-3952. ; 34:1, s. 194-206
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Journal article (peer-reviewed)abstract
- TP53 mutations are implicated in the progression of mucinous borderline tumors (MBOT) to mucinous ovarian carcinomas (MOC). Optimized immunohistochemistry (INC) for TP53 has been established as a proxy for the TP53 mutation status in other ovarian tumor types. We aimed to confirm the ability of TP53 IHC to predict TP53 mutation status in ovarian mucinous tumors and to evaluate the association of TP53 mutation status with survival among patients with MBOT and MOC. Tumor tissue from an initial cohort of 113 women with MBOT/MOC was stained with optimized IHC for TP53 using tissue microarrays (75.2%) or full sections (24.8%) and interpreted using established criteria as normal or abnormal (overexpression, complete absence, or cytoplasmic). Cases were considered concordant if abnormal IHC staining predicted deleterious TP53 mutations. Discordant tissue microarray cases were re-evaluated on full sections and interpretational criteria were refined. The initial cohort was expanded to a total of 165 MBOT and 424 MOC for the examination of the association of survival with TP53 mutation status, assessed either by TP53 IHC and/or sequencing. Initially, 82/113 (72.6%) cases were concordant using the established criteria. Refined criteria for overexpression to account for intratumoral heterogeneity and terminal differentiation improved concordance to 93.8% (106/113). In the expanded cohort, 19.4% (32/165) of MBOT showed evidence for TP53 mutation and this was associated with a higher risk of recurrence, disease-specific death, and all-cause mortality (overall survival: HR = 4.6, 95% CI 1.5-14.3, p = 0.0087). Within MOC, 61.1% (259/424) harbored a TP53 mutation, but this was not associated with survival (overall survival, p = 0.77). TP53 IHC is an accurate proxy for TP53 mutation status with refined interpretation criteria accounting for intratumoral heterogeneity and terminal differentiation in ovarian mucinous tumors. TP53 mutation status is an important biomarker to identify MBOT with a higher risk of mortality.
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- Sodergren, Erica, et al.
(author)
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The genome of the sea urchin Strongylocentrotus purpuratus.
- 2006
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In: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52
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Journal article (peer-reviewed)abstract
- We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
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- Brunet-Ratnasingham, Elsa, et al.
(author)
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Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity
- 2023
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Other publication (other academic/artistic)abstract
- Plasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized COVID-19 patients. Integrated analysis using k-means reveal four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors are delineated by high and low antibody responses. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4+ T cell frequencies. These data suggest that the “Interferon paradox” previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity.
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- Brunet-Ratnasingham, Elsa, et al.
(author)
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Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity.
- 2024
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In: Nature Communications. - 2041-1723. ; 15:1, s. 4177-
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Journal article (peer-reviewed)abstract
- Plasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized patients with COVID-19. Integrated analysis using k-means reveals four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors segregate into high and low early antibody responders. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4+ T cell frequencies. These data suggest that the "Interferon paradox" previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity.
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- Fritz, M., et al.
(author)
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Brief Communication : Future avenues for permafrost science from the perspective of early career researchers
- 2015
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In: The Cryosphere. - : Copernicus GmbH. - 1994-0416 .- 1994-0424. ; 9:4, s. 1715-1720
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Journal article (peer-reviewed)abstract
- Accelerating climate change and increased economic and environmental interests in permafrost-affected regions have resulted in an acute need for more directed permafrost research. In June 2014, 88 early career researchers convened to identify future priorities for permafrost research. This multidisciplinary forum concluded that five research topics deserve greatest attention: permafrost landscape dynamics, permafrost thermal modeling, integration of traditional knowledge, spatial distribution of ground ice, and engineering issues. These topics underline the need for integrated research across a spectrum of permafrost-related domains and constitute a contribution to the Third International Conference on Arctic Research Planning (ICARP III).
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- Lepage, O, et al.
(author)
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Differential stress coping in wild and domesticated sea trout
- 2000
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In: BRAIN BEHAVIOR AND EVOLUTION. - 0006-8977. ; 56:5, s. 259-268
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Journal article (peer-reviewed)abstract
- Offspring of wild and sea-ranched [domesticated) sea trout (Salmo trutta) originating from the same river, were reared under identical hatchery conditions from the time of fertilization. At one year of age individual fish were exposed to two standardized
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