Geodynamic effects of subducted seamount at the Manila Trench: Insights from numerical modeling

Abstract We used numerical modeling to investigate the geodynamic effects of subducted seamounts at the Manila Trench. A series of numerical modeling experiments were conducted with variable parameters, including the activation volume (Vact) and cohesion (C), which influence lithospheric rheology, the plate convergence velocity, and the age of subducting slab. Modeling results indicate that varying the Vact and C within an appropriate range have limited effects on the geodynamic process of subduction. A lower Vact allows the slab to sink more easily and results in a steeper dip angle. A slab break-off is more likely to occur under subduction at depths of 100–300 km, while the existence of a seamount further promotes the break-off process. The convergence rate is a key parameter affecting the break-off timing and depth. In contrast, under subduction where subducted oceanic plate move faster upper plate, the model results exhibit non-break-off, steady subduction. Slab age is another factor controlling break-off, where break-off time extends with slab age. A subduction without seamount will cause a ~2 Myr delay in break-off timing. We suggest that the low-velocity zone under the Manila Trench at 17o N is the result of a break-off event due to subduction of the Zhenbei-Huangyan Seamount Chain. Further to the north, such as the location at 19o N, the absence of seamount and an older oceanic crust would favor a delay in break-off timing during subduction

Evidence for rapid large-amplitude vertical motions in the Valencia Trough (Western Mediterranean) generated by 3D subduction slab roll-back

International audienceThe mechanisms controlling the Cenozoic subsidence of the Valencia Trough, located in the Western Mediterranean, are poorly understood. The Cenozoic geodynamic evolution of the Western Mediterranean is complex comprising subduction, slab roll-back, back-arc extension, collision, and lithosphere delamination. We investigate the subsidence of a regionally observed unconformity, here referred to as the Miocene Unconformity, which separates Mesozoic from latest Palaeogene to Neogene sediments. Using a dense grid of seismic reflection data, well data and 3D flexural backstripping, we show that the Miocene Unconformity in the SW Valencia Trough subsided by more than 1.5 km to the present day at an average rate of 90 m/Myr. The absence of Cenozoic extensional faults affecting the basement shown by seismic data indicates that this rapid subsidence is not caused by Cenozoic rifting or remaining Mesozoic post-rift thermal subsidence. Neither can this subsidence be explained by subduction dynamic subsidence or flexural loading related to the thin-skin Betic fold and thrust belt which only affects subsidence observed near the deformation front. We interpret the 1.5 km subsidence of the Miocene Unconformity as the collapse of a back-arc transient uplift event. Erosion during this uplift, resulting in the formation of the Miocene Unconformity, is estimated to exceed 4 km. Transient uplift was likely caused by heating of back-arc lithosphere and asthenosphere, combined with mantle dynamic uplift, both caused by segmentation of Tethyan subduction resulting in slab tear. Subsidence resulted from thermal equilibration and the removal of mantle flow dynamic support Tethyan subduction slab roll-back. We propose that our observations and interpretation of rapid back-arc km-scale uplift and collapse have global applicability for other back-arc regions experiencing subduction segmentation and slab tear during subduction slab roll-back

Transcriptome Sequencing Reveals Key Pathways and Genes Associated with Cisplatin Resistance in Lung Adenocarcinoma A549 Cells.

Acquired resistance to cisplatin-based chemotherapy frequently occurs in patients with non-small cell lung cancer, and the underlying molecular mechanisms are not well understood. The aim of this study was to investigate whether a distinct gene expression pattern is associated with acquired resistance to cisplatin in human lung adenocarcinoma. Whole-transcriptome sequencing was performed to compare the genome-wide gene expression patterns of the human lung adenocarcinoma A549 cisplatin-resistant cell line A549/DDP with those of its progenitor cell line A549. A total of 1214 differentially expressed genes (DEGs) were identified, 656 of which were upregulated and 558 were downregulated. Functional annotation of the DEGs in the Kyoto Encyclopedia of Genes and Genomes database revealed that most of the identified genes were enriched in the PI3K/AKT, mitogen-activated protein kinase, actin cytoskeleton regulation, and focal adhesion pathways in A549/DDP cells. These results support previous studies demonstrating that the pathways regulating cell proliferation and invasion confer resistance to chemotherapy. Furthermore, the results proved that cell adhesion and cytoskeleton regulation is associated with cisplatin resistance in human lung cancer. Our study provides new promising biomarkers for lung cancer prognosis and potential therapeutic targets for lung cancer treatment

CCNB1IP1 prevents ubiquitination‐mediated destabilization of MYCN and potentiates tumourigenesis of MYCN‐amplificated neuroblastoma

Abstract Background MYCN amplification as a common genetic alteration that correlates with a poor prognosis for neuroblastoma (NB) patients. However, given the challenge of directly targeting MYCN, indirect strategies to modulate MYCN by interfering with its cofactors are attractive in NB treatment. Although cyclin B1 interacting protein 1 (CCNB1IP1) has been found to be upregulated in MYCN‐driven mouse NB tissues, its regulation with MYCN and collaboration in driving the biological behaviour of NB remains unknown. Methods To evaluate the expression and clinical significance of CCNB1IP1 in NB patients, public datasets, clinical NB samples and cell lines were explored. MTT, EdU incorporation, colony and tumour sphere formation assays, and a mouse xenograft tumour model were utilized to examine the biological function of CCNB1IP1. The reciprocal manipulation of CCNB1IP1 and MYCN and the underlying mechanisms involved were investigated by gain‐ and loss‐of‐function approaches, dual‐luciferase assay, chromatin immunoprecipitation (CHIP) and co‐immunoprecipitation (Co‐IP) experiments. Results CCNB1IP1 was upregulated in MYCN‐amplified (MYCN‐AM) NB cell lines and patients‐derived tumour tissues, which was associated with poor prognosis. Phenotypic studies revealed that CCNB1IP1 facilitated the proliferation and tumourigenicity of NB cells in cooperation with MYCN in vitro and in vivo. Mechanistically, MYCN directly mediates the transcription of CCNB1IP1, which in turn attenuated the ubiquitination and degradation of MYCN protein, thus enhancing CCNB1IP1‐MYCN cooperativity. Moreover, CCNB1IP1 competed with F box/WD‐40 domain protein 7 (FBXW7) for MYCN binding and enabled MYCN‐mediated tumourigenesis in a C‐terminal domain‐dependent manner. Conclusions Our study revealed a previously uncharacterized mechanism of CCNB1IP1‐mediated MYCN protein stability and will provide new prospects for precise treatment of MYCN‐AM NB based on MYCN‐CCNB1IP1 interaction

Cell morphology differences between A549 and A549/DDP cells.

<p>Micrographs showing A549 and A549/DDP cells cultured for 3 days in the absence or presence of cisplatin (10μg/mL).</p

COG function classification of the consensus sequences.

<p>The COG categories are shown on the horizontal axis and gene numbers and proportions are plotted on the vertical axis.</p

KEGG categories of HepG2/DDP cells DEGs.

<p>The vertical axis lists the names of the metabolic pathways in the KEGG database, and the horizontal axis shows the proportion of annotated genes in each pathway versus the total number of annotated genes.</p

GO classification.

<p>Annotation statistics of differentially expressed genes in the secondary node of GO. The horizontal axis shows the secondary nodes of three categories in GO. The vertical axis displays the percentage of annotated genes versus the total gene number. The red columns display annotation information of the total genes and the blue columns represent annotation information of the differentially expressed genes only.</p

Statistical summary of transcriptome sequencing.

<p>Statistical summary of transcriptome sequencing.</p