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- De Vleeschouwer, David, et al.
(författare)
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The amplifying effect of Indonesian Throughflow heat transport on Late Pliocene Southern Hemisphere climate cooling
- 2018
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Ingår i: Earth and Planetary Science Letters. - : ELSEVIER SCIENCE BV. - 0012-821X .- 1385-013X. ; 500, s. 15-27
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Tidskriftsartikel (refereegranskat)abstract
- An unusually short glaciation interrupted the warm Pliocene around 3.3 Ma (Marine Isotope Stage (MIS) M2). Different hypotheses exist to explain why this glaciation event was so pronounced, and why the global climate system returned to warm Pliocene conditions relatively quickly afterwards. One of these proposed mechanisms is a reduced equator-to-pole heat transfer, in response to a tectonically reduced Indonesian Throughflow (ITF). The ITF is a critical part of the global thermohaline ocean circulation, transporting heat from the Indo-Pacific Warm Pool to the Indian Ocean. When ITF connectivity is reduced, the water and heat supply for the Leeuwin Current, flowing poleward along Australia's west coast, is also diminished. To assess the possible relationship between mid-Pliocene glaciations and latitudinal heat transport through the Indonesian Throughflow, we constructed a multi-proxy orbital scale record for the 3.7-2.8 Ma interval from International Ocean Discovery Program (IODP) Site U1463, off northwest Australia. The comparison of the Site U1463 record with paleoclimate records from nearby Site 763 and West Pacific Warm Pool Site 806 allows for a detailed regional reconstruction of Pliocene paleoceanography and thus for testing the proposed hypothesis. An astronomically-paced decrease in potassium content characterizes the late Pliocene interval of U1463. This record documents the increasing aridity of northwest Australia, periodically alleviated by reinforced summer monsoon precipitation under summer insolation maxima. The 3180 record of the planktonic foraminifer Globigerinoides sacculifer correlates exceptionally well with the sea surface temperature (SST) record from Site 806 in the West Pacific Warm Pool, even during MIS M2. Hence, Site U1463 preserves an uninterrupted ITF signal even during Pliocene glaciations. However, the U1463 delta O-18(G.sacculifer) record exhibits a 0.5 parts per thousand offset with the nearby Site 763A record around MIS M2. This implies that Site 763A, about 500 km west of U1463, more closely tracks Indian Ocean SST records across MIS M2. The U1463 data reveal that heat-transport through the Indonesian Throughflow did not shut down completely during MIS M2, but rather its intensity decreased prior to and during MIS M2, causing Site 763A to temporarily reflect an Indian Ocean, rather than an ITF signal. We conclude that ITF variability significantly influenced latitudinal heat transport by means of the Leeuwin Current and hence contributed to the relative intensity of MIS M2. We propose the ITF valve between the Pacific and Indian Ocean as a positive feedback mechanism, in which an initial sea level lowering reduces ITF heat transport, in turn amplifying global cooling by advancing the thermal isolation of Antarctica.
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| 2. |
- Engel, Lawrence S., et al.
(författare)
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Prediagnostic serum organochlorine insecticide concentrations and primary liver cancer : A case–control study nested within two prospective cohorts
- 2019
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 145:9, s. 2360-2371
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Tidskriftsartikel (refereegranskat)abstract
- Although experimental evidence indicates that certain organochlorine insecticides are hepatocarcinogens, epidemiologic evidence for most of these chemicals is very limited. We estimated associations, using prospectively collected sera, between organochlorine insecticide concentrations and cancer registry-identified primary liver cancer in two cohorts, one from the United States and one from Norway. In nested case–control studies, we used sera collected in the 1960s-1980s from 136 cases and 408 matched controls from the Kaiser Permanente Northern California Multiphasic Health Checkup (MHC) cohort and 84 cases and 252 matched controls from the population-based Norwegian Janus cohort. We measured concentrations of nine organochlorine insecticides/metabolites and markers of hepatitis B and C in sera. Adjusted odds ratios (OR) and 95% confidence intervals (CI) for tertiles of lipid-corrected organochlorines were calculated for each cohort using conditional logistic regression. Among MHC participants with sera from the 1960s, there was a suggestive exposure-response trend for trans-nonachlor (second and third tertile of analyte ORs = 1.63 and 1.95, respectively; p-trend = 0.08) and a nonsignificantly elevated risk for the highest tertile of oxychlordane (OR = 1.87). Among Janus participants with sera from the 1970s, we observed an apparent trend for p,p’-DDT (second and third tertile ORs = 1.70 and 2.14, respectively; p-trend = 0.15). We observed little consistency in patterns of association between the cohorts. We found limited evidence that exposure to p,p’-DDT and chlordane-related oxychlordane and trans-nonachlor may be associated with increased risk of primary liver cancer. However, the modest strength of these associations and their lack of concordance between cohorts necessitate caution in their interpretation.
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| 3. |
- Liao, Xiwen, et al.
(författare)
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Integrated analysis of competing endogenous RNA network revealing potential prognostic biomarkers of hepatocellular carcinoma
- 2019
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Ingår i: Journal of Cancer. - : Ivyspring International Publisher. - 1837-9664. ; 10:14, s. 3267-3283
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The goal of our study is to identify a competing endogenous RNA (ceRNA) network using dysregulated RNAs between HCC tumors and the adjacent normal liver tissues from The Cancer Genome Atlas (TCGA) datasets, and to investigate underlying prognostic indicators in hepatocellular carcinoma (HCC) patients. Methods: All of the RNA- and miRNA-sequencing datasets of HCC were obtained from TCGA, and dysregulated RNAs between HCC tumors and the adjacent normal liver tissues were investigated by DESeq and edgeR algorithm. Survival analysis was used to confirm underlying prognostic indicators. Results: In the present study, we constructed a ceRNA network based on 16 differentially expressed genes (DEGs), 7 differentially expressed microRNAs and 34 differentially expressed long non-coding RNAs (DELs). Among these dysregulated RNAs, three DELs (AP002478.1, HTR2A-AS1, and ERVMER61-1) and six DEGs (enhancer of zeste homolog 2 [EZH2], kinesin family member 23 [KIF23], chromobox 2 [CBX2], centrosomal protein 55 [CEP55], cell division cycle 25A [CDC25A], and claspin [CLSPN]) were used for construct a prognostic signature for HCC overall survival (OS), and performed well in HCC OS (adjusted P<0.0001, adjusted hazard ratio = 2.761, 95% confidence interval = 1.838-4.147). Comprehensive survival analysis demonstrated that this prognostic signature may be act as an independent prognostic indicator of HCC OS. Functional assessment of these dysregulated DEGs in the ceRNA network and gene set enrichment of this prognostic signature suggest that both were enriched in the biological processes and pathways of the cell cycle, cell division and cell proliferation. Conclusions: Our current study constructed a ceRNA network for HCC, and developed a prognostic signature that may act as an independent indicator for HCC OS.
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| 5. |
- Seelig, Davis M, et al.
(författare)
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Constitutive activation of alternative nuclear factor kappa B pathway in canine diffuse large B-cell lymphoma contributes to tumor cell survival and is a target of new adjuvant therapies
- 2017
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 58:7, s. 1702-1710
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Tidskriftsartikel (refereegranskat)abstract
- Activation of the classical nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway is a common molecular event observed in both human and canine diffuse large B-cell lymphoma (DLBCL). Although the oncogenic potential of the alternative NFκB pathway (ANFκBP) has also been recently identified in DLBCL, its precise role in tumor pathogenesis and potential as a treatment target is understudied. We hypothesized that up-regulation of the ANFκBP plays an important role in the proliferation and survival of canine DLBCL cells, and we demonstrate that the ANFκBP is constitutively active in primary canine DLBCL samples and a cell line (CLBL1). We further demonstrate that a small interfering RNA inhibits the activation of the NFκB pathway and induces apoptosis in canine DLBCL cells. In conclusion, the ANFκBP facilitates survival of canine DLBCL cells, and thus, dogs with spontaneous DLBCL can provide a useful large animal model to study therapies targeting the ANFκBP.
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