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| 2. |
- Berrout, Jonathan, et al.
(författare)
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TRPA1-FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Recent evidence suggests that the ion channel TRPA1 is implicated in lung adenocarcinoma (LUAD), where its role and mechanism of action remain unknown. We have previously established that the membrane receptor FGFR2 drives LUAD progression through aberrant protein-protein interactions mediated via its C-terminal proline-rich motif. Here we report that the N-terminal ankyrin repeats of TRPA1 directly bind to the C-terminal proline-rich motif of FGFR2 inducing the constitutive activation of the receptor, thereby prompting LUAD progression and metastasis. Furthermore, we show that upon metastasis to the brain, TRPA1 gets depleted, an effect triggered by the transfer of TRPA1-targeting exosomal microRNA (miRNA-142-3p) from brain astrocytes to cancer cells. This downregulation, in turn, inhibits TRPA1-mediated activation of FGFR2, hindering the metastatic process. Our study reveals a direct binding event and characterizes the role of TRPA1 ankyrin repeats in regulating FGFR2-driven oncogenic process; a mechanism that is hindered by miRNA-142-3p.
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| 3. |
- Horsley, Alex R, et al.
(författare)
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Effects of cystic fibrosis lung disease on gas mixing indices derived from alveolar slope analysis.
- 2008
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Ingår i: Respiratory physiology & neurobiology. - : Elsevier BV. - 1569-9048. ; 162:3, s. 197-203
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Tidskriftsartikel (refereegranskat)abstract
- S(cond) and S(acin) are derived from analysis of concentration-normalized phase III slopes (Sn(III)) of a multiple breath inert gas washout. Studies in healthy and COPD subjects suggest these reflect ventilation heterogeneity in conducting and acinar airway zones respectively, but similar studies in cystic fibrosis (CF) are lacking. S(cond), S(acin) and lung clearance index (LCI, a measure of overall gas mixing efficiency) were measured in 22 adults and 18 children with CF and 17 adult and 29 child controls. Plethysmography and gas transfer measurements were performed in adults, and spirometry in all subjects. S(cond) was elevated in almost all CF patients, including children with mild disease and normal LCI. However, S(cond) did not correlate with other measurements and appeared to reach a maximum; further increase in ventilation heterogeneity being restricted to S(acin). The nature and/or severity of CF lung disease may invalidate assumptions underlying the ability to separate phase III slope analysis of ventilation heterogeneity into proximal and peripheral components, and LCI may be a better indicator of gas mixing in this population.
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| 4. |
- Jimenez Berrocoso, Alvaro, et al.
(författare)
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The Lindi Formation (upper Albian-Coniacian) and Tanzania Drilling Project Sites 36-40 (Lower Cretaceous to Paleogene) : Lithostratigraphy, biostratigraphy and chemostratigraphy
- 2015
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Ingår i: Journal of African earth sciences. - : Elsevier BV. - 1464-343X. ; 101, s. 282-308
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Tidskriftsartikel (refereegranskat)abstract
- The 2009 Tanzania Drilling Project (TDP) expedition to southeastern Tanzania cored a total of 572.3 m of sediments at six new mid-Cretaceous to mid-Paleocene boreholes (TDP Sites 36, 37, 38, 39, 40A, 40B). Added to the sites drilled in 2007 and 2008, the new boreholes confirm the common excellent preservation of planktonic and benthic foraminifera and calcareous nannofossils from core samples that will be used for biostratigraphy, evolutionary studies, paleoceanography and climatic reconstructions from the Tanzanian margin, with implications elsewhere. The new sites verify the presence of a relatively expanded Upper Cretaceous succession in the region that has allowed a new stratigraphic unit, named here as the Lindi Formation (Fm), to be formally defined. The Lindi Fm (upper Albian to Coniacian), extending similar to 120 km between Kilwa and Lindi, comprises a 335-m-thick, outer-shelf to upper-slope unit, consisting of dark gray claystone and siltstone interbeds, common finely-laminated intervals, minor cm-thick sandstones and up to 2.6% organic carbon in the Turonian. A subsurface, composite stratotype section is proposed for the Lindi Fm, with a gradational top boundary with the overlying Nangurukuru Fm (Santonian to Maastrichtian) and a sharp bottom contact with underlying upper Albian sandstones. The section cored at TDP Sites 36 and 38 belongs to the Lindi Fm and are of lower to middle Turonian age (planktonic foraminifera Whiteinella archaeocretacea to Helvetoglobotruncana helvetica Zones and nannofossils subzones UC6b +/- UC7). The lower portion of TDP Site 39 (uppermost part of the Lindi Fm) is assigned to the lower to upper Coniacian (planktonic foraminifera Dicarinella concavata Zone and nannofossils zone UC 10), while the remaining part of this site is attributed to the Coniacian-Santonian transition and younger Santonian (planktonic foraminifera D. asymetrica Zone and upper part of nannofossils zone UC10). TDP Site 37 recovered relatively expanded (150 m thick), monotonous calcareous claystones from the lower to upper Maastrichtian (planktonic foraminifera Pseudoguembelina palpebra to Abathomphalus mayaroensis Zones and nannofossils zones UC19 to UC20a(TP)) that were separated by a hiatus and/or a faulted contact from overlying brecciated carbonates of the Selandian (middle Paleocene: PF Zone P3 and nannofossil zone NP5). The lower portion of TDP Sites 40A and 40B recovered sandstones and conglomerates barren of microfossils. Their overlying parts were assigned to incomplete sections of the nannofossil zones NC6A to NC8 (uppermost Barremian to lower Albian). Benthic foraminiferal assemblages allowed the Barremian to lower Aptian to be identified in TDP Sites 40A and 40B, while the upper Aptian to middle Albian (Hedbergella trocoidea to Ticinella primula Zones) were assigned using planktonic foraminifera. Cores recovered at TDP 39 (Coniacian-Santonian) and at TDP Sites 40A and 40B (Barremian-middle Albian) represent the first time that these two intervals have been continuously cored and publicly documented in Tanzania. Bulk sediment isotope records generated for the new sites show lower delta O-18(carb) values in the Turonian and Santonian (similar to-3.5 parts per thousand to -5 parts per thousand) than in the Maastrichtian (similar to-3 parts per thousand), a situation consistent with extreme global warmth in the older intervals and cooling toward the end of the Cretaceous. Also, similar to Turonian sites from previous TDP expeditions, a negative delta C-13(org) excursion was detected across the W. archaeocretacea-H. helvetica boundary of TDP Site 36 (close to, but above, the Cenomanian-Turonian boundary). This excursion probably responded to local processes in the region, but it is unknown whether they were related to the recovery phase from Ocean Anoxic Event 2.
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| 5. |
- Schulte, Peter, et al.
(författare)
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Cretaceous Extinctions: Evidence Overlooked Response
- 2010
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 328:5981, s. 975-976
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Schulte, Peter, et al.
(författare)
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The Chicxulub Asteroid Impact and Mass Extinction at the Cretaceous-Paleogene Boundary
- 2010
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 327:5970, s. 1214-1218
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Tidskriftsartikel (refereegranskat)abstract
- The Cretaceous-Paleogene boundary similar to 65.5 million years ago marks one of the three largest mass extinctions in the past 500 million years. The extinction event coincided with a large asteroid impact at Chicxulub, Mexico, and occurred within the time of Deccan flood basalt volcanism in India. Here, we synthesize records of the global stratigraphy across this boundary to assess the proposed causes of the mass extinction. Notably, a single ejecta-rich deposit compositionally linked to the Chicxulub impact is globally distributed at the Cretaceous-Paleogene boundary. The temporal match between the ejecta layer and the onset of the extinctions and the agreement of ecological patterns in the fossil record with modeled environmental perturbations (for example, darkness and cooling) lead us to conclude that the Chicxulub impact triggered the mass extinction.
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