| 1. |
- Hudson, Thomas J., et al.
(författare)
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International network of cancer genome projects
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
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Tidskriftsartikel (refereegranskat)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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| 2. |
- Zaidi, Syed H., et al.
(författare)
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Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival
- 2020
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR=0.42, 95% CI: 0.21-0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR=1.53, 95% CI: 1.21-1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features. Large scale sequencing study is of paramount importance to unravel the heterogeneity of colorectal cancer. Here, the authors sequenced 205 cancer genes in more than 2000 tumours and identified additional mutated driver genes, determined that mutational burden and specific mutations in TP53 are associated with survival odds.
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| 3. |
- Cunningham, Kelly A, et al.
(författare)
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CTA1-DD is an effective adjuvant for targeting anti-chlamydial immunity to the murine genital mucosa.
- 2009
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Ingår i: Journal of reproductive immunology. - : Elsevier BV. - 1872-7603 .- 0165-0378. ; 81:1, s. 34-8
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Tidskriftsartikel (refereegranskat)abstract
- Chlamydia trachomatis is a significant human pathogen with potentially severe disease sequelae in the genital tract, including infertility. A successful vaccine will need to effectively target immunity to the genital mucosa. Intranasal immunisation with cholera toxin (CT) can target immunity to the genital tract, but has the potential to cause neurological side effects. CTA1-DD is a non-toxic potent mucosal adjuvant which combines the enzymatic properties of CT, with a B cell targeting moiety. Here, we demonstrate that intranasal immunisation with CTA1-DD and chlamydial Major Outer Membrane Protein (MOMP) results in the induction of neutralising systemic and mucosal antibodies, and reduces the level of chlamydial shedding following intravaginal challenge with Chlamydia muridarum. Thus, CTA1-DD is an effective adjuvant for vaccine development against Chlamydia trachomatis, and possibly also a range of other genital pathogens.
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| 4. |
- Demichev, Vadim, et al.
(författare)
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A time-resolved proteomic and prognostic map of COVID-19
- 2021
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Ingår i: Cell Systems. - : Elsevier BV. - 2405-4712 .- 2405-4720. ; 12:8, s. 780-794.e7
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.
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| 5. |
- O'Meara, Connor P, et al.
(författare)
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Immunity against a Chlamydia infection and disease may be determined by a balance of IL-17 signaling.
- 2014
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Ingår i: Immunology and cell biology. - : Wiley. - 1440-1711 .- 0818-9641. ; 92:3, s. 287-297
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Tidskriftsartikel (refereegranskat)abstract
- Most vaccines developed against Chlamydia using animal models provide partial protection against a genital tract infection. However, protection against the oviduct pathology associated with infertility is highly variable and often has no defining immunological correlate. When comparing two adjuvants (CTA1-DD and a combination of Cholera toxin plus CpG-oligodeoxynucleotide-CT/CpG) combined with the chlamydial major outer membrane protein (MOMP) antigen and delivered via the intranasal (IN), sublingual (SL) or transcutaneous (TC) routes, we identified two vaccine groups with contrasting outcomes following infection. SL immunization with MOMP/CTA1-DD induced a 70% reduction in the incidence of oviduct pathology, without significantly altering the course of infection. Conversely, IN immunization with MOMP/CT/CpG prevented an ascending infection, but not the oviduct pathology. This anomaly presented a unique opportunity to study the mechanisms by which vaccines can prevent oviduct pathology, other than by controlling the infection. The IL-17 signaling in the oviducts was found to associate with both the enhancement of immunity to infection and the development of oviduct pathology. This conflicting role of IL-17 may provide some explanation for the discordance in protection between infection and disease and suggests that controlling immunopathology, as opposed to the rapid eradication of the infection, may be essential for an effective human chlamydial vaccine that prevents infertility.Immunology and Cell Biology advance online publication, 24 December 2013; doi:10.1038/icb.2013.92.
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| 6. |
- Quintero, Raiza R., et al.
(författare)
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Shocked quartz in sandstone from the buried Ilkurlka impact structure, Officer Basin, Western Australia
- 2023
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Ingår i: Meteoritics and Planetary Science. - 1086-9379. ; 59:1, s. 68-87
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Tidskriftsartikel (refereegranskat)abstract
- The Ilkurlka structure is an ~12 km diameter buried circular aeromagnetic anomaly within the Officer Basin in Western Australia. Prior studies postulated a range of origins, including meteorite impact. We report the presence of pervasive deformation in the first drill cores from the structure. Brecciated sandstone and siltstone contain arrays of quartz grains with concussion fractures and rare shocked quartz grains with planar deformation features (PDF). Universal stage measurements of two quartz grains reveal one grain with PDF parallel to (0001) orientation and three PDF sets parallel to (Formula presented.). A second grain contains three PDF sets parallel to (Formula presented.) and one set parallel to (Formula presented.). The shocked grains are interpreted to have formed in situ, rather than representing transported detrital shocked grains. These results suggest local shock compression of at least 10 GPa; however, preservation of primary porosity and overall paucity of shocked grains may indicate lower mean shock pressures. (U-Th)/He dating of 58 apatite grains from four samples across both cores shows a dominant age population at ~265 Ma and a minor age population at ~135 Ma. These dates overlap with regional events and thus do not provide an unambiguous impact age. An upper Carboniferous to lower Permian maximum impact age is provisionally proposed based on inferred missing target rock stratigraphy.
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