The Rational Solutions and Quasi-Periodic Wave Solutions as well as Interactions of N

The exact rational solutions, quasi-periodic wave solutions, and N-soliton solutions of 3 + 1 dimensional Jimbo-Miwa equation are acquired, respectively, by using the Hirota method, whereafter the rational solutions are also called algebraic solitary waves solutions and used to describe the squall lines phenomenon and explained possible formation mechanism of the rainstorm formation which occur in the atmosphere, so the study on the rational solutions of soliton equations has potential application value in the atmosphere field; the soliton fission and fusion are described based on the resonant solution which is a special form of the N-soliton solutions. At last, the interactions of the solitons are shown with the aid of N-soliton solutions

\u3cem\u3eLkb1\u3c/em\u3e Inactivation Drives Lung Cancer Lineage Switching Governed by Polycomb Repressive Complex 2

Adenosquamous lung tumours, which are extremely poor prognosis, may result from cellular plasticity. Here, we demonstrate lineage switching of KRAS+ lung adenocarcinomas (ADC) to squamous cell carcinoma (SCC) through deletion of Lkb1 (Stk11) in autochthonous and transplant models. Chromatin analysis reveals loss of H3K27me3 and gain of H3K27ac and H3K4me3 at squamous lineage genes, including Sox2, ΔNp63 and Ngfr. SCC lesions have higher levels of the H3K27 methyltransferase EZH2 than the ADC lesions, but there is a clear lack of the essential Polycomb Repressive Complex 2 (PRC2) subunit EED in the SCC lesions. The pattern of high EZH2, but low H3K27me3 mark, is also prevalent in human lung SCC and SCC regions within ADSCC tumours. Using FACS-isolated populations, we demonstrate that bronchioalveolar stem cells and club cells are the likely cells-of-origin for SCC transitioned tumours. These findings shed light on the epigenetics and cellular origins of lineage-specific lung tumours

Surface Motion and Topographic Effects on Ice Thickness Inversion for High Mountain Asia Glaciers: A Comparison Study from Three Numerical Models

Several studies have evaluated the accuracy of ice thickness model inversions, but the effects of surface velocity and topographic factors have not been fully studied. Because of the important potential of models for estimating regional and global ice thickness, the influence of the characteristics of the glaciers themselves on the models is unknown. Therefore, we estimated the thickness of 10 glaciers in HMA based on remote sensing data using the GlabTop2, GV22, and VOLTA models, and we analyzed the factors affecting accuracy. The first two models are representative of the widely used shallow ice approximation and laminar flow theory, and the latter is a new model based on shallow ice approximation. The results show that the RMSEs for GlabTop2, VOLTA, and GV22 are 36.6 m, 56.8 m, and 63.2 m, respectively. The accuracy of the three models differed obviously under the influence of different slopes, aspects, and surface velocities. In contrast to glaciers with higher surface velocities, GV22 is more suitable for glaciers with smaller surface velocities, and the accuracy of the model is significantly reduced when surface velocities are greater than 50 m/yr. Aspect has an effect on the accuracy of the GV22 ice thickness inversion but not on the other models. Ice thicknesses estimated using the three models is more reliable at surface slopes of 16–24°. These three models do not apply to gentle glaciers such as icecaps. Our study provides an important reference for choosing a suitable model to invert the glacier thickness in HMA

Mst1 is an interacting protein that mediates PHLPPs\u27 induced apoptosis

PHLPP1 and PHLPP2 phosphatases exert their tumor-suppressing functions by dephosphorylation and inactivation of Akt in several breast cancer and glioblastoma cells. However, Akt, or other known targets of PHLPPs that include PKC and ERK, may not fully elucidate the physiological role of the multifunctional phosphatases, especially their powerful apoptosis induction function. Here, we show that PHLPPs induce apoptosis in cancer cells independent of the known targets of PHLPPs. We identified Mst1 as a binding partner that interacts with PHLPPs both in vivo and in vitro. PHLPPs dephosphorylate Mst1 on the T387 inhibitory site, which activate Mst1 and its downstream effectors p38 and JNK to induce apoptosis. The same T387 site can be phosphorylated by Akt. Thus, PHLPP, Akt, and Mst1 constitute an autoinhibitory triangle that controls the fine balance of apoptosis and proliferation that is cell type and context dependent

Overcoming Resistance to Dual Innate Immune and MEK Inhibition Downstream of KRAS

Despite extensive efforts, oncogenic KRAS remains resistant to targeted therapy. Combined downstream RAL-TBK1 and MEK inhibition induces only transient lung tumor shrinkage in KRAS-driven genetically engineered mouse models (GEMMs). Using the sensitive KRAS;LKB1 (KL) mutant background, we identify YAP1 upregulation and a therapy-induced secretome as mediators of acquired resistance. This program is reversible, associated with H3K27 promoter acetylation, and suppressed by BET inhibition, resensitizing resistant KL cells to TBK1/MEK inhibition. Constitutive YAP1 signaling promotes intrinsic resistance in KRAS;TP53 (KP) mutant lung cancer. Intermittent treatment with the BET inhibitor JQ1 thus overcomes resistance to combined pathway inhibition in KL and KP GEMMs. Using potent and selective TBK1 and BET inhibitors we further develop an effective therapeutic strategy with potential translatability to the clinic