Aneuploid Embryonic Stem Cells Drive Teratoma Metastasis

Aneuploidy, a deviation of the chromosome number from euploidy, is one of the hallmarks of cancer. High levels of aneuploidy are generally correlated with metastasis and poor prognosis in cancer patients. However, the causality of aneuploidy in cancer metastasis remains to be explored. Here we demonstrate that teratomas derived from aneuploid murine embryonic stem cells (ESCs), but not from isogenic diploid ESCs, disseminated to multiple organs, for which no additional copy number variations were required. Notably, no cancer driver gene mutations were identified in any metastases. Aneuploid circulating teratoma cells were successfully isolated from peripheral blood and showed high capacities for migration and organ colonization. Single-cell RNA sequencing of aneuploid primary teratomas and metastases identified a unique cell population with high stemness that was absent in diploid ESCs-derived teratomas. Further investigation revealed that aneuploid cells displayed decreased proteasome activity and overactivated endoplasmic reticulum (ER) stress during differentiation, thereby restricting the degradation of proteins produced from extra chromosomes in the ESC state and causing differentiation deficiencies. Noticeably, both proteasome activator Oleuropein and ER stress inhibitor 4-PBA can effectively inhibit aneuploid teratoma metastasis

A ROP GTPase-Dependent Auxin Signaling Pathway Regulates the Subcellular Distribution of PIN2 in Arabidopsis Roots

SummaryPIN-FORMED (PIN) protein-mediated auxin polar transport is critically important for development, pattern formation, and morphogenesis in plants. Auxin has been implicated in the regulation of polar auxin transport by inhibiting PIN endocytosis [1, 2], but how auxin regulates this process is poorly understood. Our genetic screen identified the Arabidopsis SPIKE1 (SPK1) gene whose loss-of-function mutations increased lateral root density and retarded gravitropic responses, as do pin2 knockout mutations [3]. SPK1 belongs to the conserved DHR2-Dock family of Rho guanine nucleotide exchange factors [4–6]. The spk1 mutations induced PIN2 internalization that was not suppressed by auxin, as did the loss-of-function mutations for Rho-like GTPase from Plants 6 (ROP6)-GTPase or its effector RIC1. Furthermore, SPK1 was required for auxin induction of ROP6 activation. Our results have established a Rho GTPase-based auxin signaling pathway that maintains PIN2 polar distribution to the plasma membrane via inhibition of its internalization in Arabidopsis roots. Our findings provide new insights into signaling mechanisms that underlie the regulation of the dynamic trafficking of PINs required for long-distance auxin transport and that link auxin signaling to PIN-mediated pattern formation and morphogenesis

Investigación sobre el establecimiento de un modelo de predicción de subsidencia minera bajo una capa gruesa inestable y su método de inversión de parámetros

Most of the coal mining in China is underground, which will inevitably cause surface deformation and trigger a series of geological disasters. Therefore, it is essential to find a suitable method to forecast the ground sinking caused by underground mining. The most commonly used prediction model in China is the probability integral model (PIM). But when this model is used in the geological condition of mining under thick loose layers, the predicted edge of the sinking basin will converge faster than the actual measured sinking situation. A geometric model (GM) with a similar model shape as the PIM but with a larger boundary value was established in this paper to solve this problem. Then an improved cuckoo search algorithm (ICSA) was proposed in this paper to calculate the GM parameters. The stability and reliability of the ICSA were verified through a simulated working face. At last, the ICSA, in combination with the GM and the PIM, was used to fit 6 working faces with the geological mining condition of thick loose layers in the Huainan mining area. The results prove that GM can solve the above-mentioned PIM problem when it is used in geological mining conditions of thick loose layers. And it was obtained through comparative analysis that the GM and the PIM parameters can take the same value except for the main influence radius.La mayor parte de la minería del carbón en China es subterránea, lo que inevitablemente causa deformaciones en la superficie y desencadena desastres geológicos. Por lo tanto, es necesario encontrar un método adecuado para pronosticar el hundimiento del suelo causado por la minería subterránea. El modelo de predicción más utilizado en China es el modelo integral de probabilidad (PIM). Pero cuando este modelo se utiliza en la condición geológica de la minería bajo capas gruesas inetables, el borde previsto de la cuenca de hundimiento converge más rápido que la situación de hundimiento medida. Para resolver este problema, en este artículo se estableció un modelo geométrico (GM) que tiene una forma de modelo similar a la del PIM pero que tiene un valor límite mayor. En este trabajo se propuso un algoritmo de búsqueda de cuco mejorado (ICSA) para calcular los parámetros de GM, y se verificó la estabilidad y confiabilidad del ICSA a través de una frente de trabajo simulado. Por último, el ICSA en combinación con el GM y el PIM se utilizaron para ajustar 6 caras de trabajo con la condición de minería geológica de capas gruesas sueltas en el área minera de Huainan. Los resultados demuestran que el GM puede resolver el problema de PIM mencionado anteriormente cuando se utiliza en las condiciones de minería geológica de capas gruesas inestables. Y se obtuvo mediante análisis comparativo que los parámetros del GM y del PIM pueden tomar el mismo valor excepto por el radio de influencia principal

Cortical Microtubule Organization during Petal Morphogenesis in Arabidopsis

Cortical microtubules guide the direction and deposition of cellulose microfibrils to build the cell wall, which in turn influences cell expansion and plant morphogenesis. In the model plant Arabidopsis thaliana (Arabidopsis), petal is a relatively simple organ that contains distinct epidermal cells, such as specialized conical cells in the adaxial epidermis and relatively flat cells with several lobes in the abaxial epidermis. In the past two decades, the Arabidopsis petal has become a model experimental system for studying cell expansion and organ morphogenesis, because petals are dispensable for plant growth and reproduction. Recent advances have expanded the role of microtubule organization in modulating petal anisotropic shape formation and conical cell shaping during petal morphogenesis. Here, we summarize recent studies showing that in Arabidopsis, several genes, such as SPIKE1, Rho of plant (ROP) GTPases, and IPGA1, play critical roles in microtubule organization and cell expansion in the abaxial epidermis during petal morphogenesis. Moreover, we summarize the live-confocal imaging studies of Arabidopsis conical cells in the adaxial epidermis, which have emerged as a new cellular model. We discuss the microtubule organization pattern during conical cell shaping. Finally, we propose future directions regarding the study of petal morphogenesis and conical cell shaping

Analysis of D-Q small-signal impedance of back-to-back frequency converter

The back-to-back frequency converter plays a vital role in the formation of the fractional frequency transmission system Despite their numerous advantages, however, impacted by the unique impedance characteristics of power electronics, the wide-band oscillations occur more frequency as well as more common recently, which have posed great challenges to the system operation and raised great concern over the researchers worldwide. To address this issue and properly investigate the impedance characteristics of the back-to-back frequency converter, this manuscript establishes the small-signal impedance of the back-to-back frequency converter with inner current control loop and outer voltage/power control loop in the synchronous reference (dq) frame. Then, by using the impedance model and determinant-based General Nyquist Criterion (GNC), the stability assessment and instability cause identification are studied. Finally, the analysis presented in this paper is verified based on frequency and time-domain simulations in the MATLAB/Simulink environment

ABP1 and ROP6 GTPase signaling regulate clathrin-mediated endocytosis in Arabidopsis roots

The dynamic spatial and temporal distribution of the crucial plant signaling molecule auxin is achieved by feedback coordination of auxin signaling and intercellular auxin transport pathways [1, 2]. Developmental roles of auxin have been attributed predominantly to its effect on transcription; however, an alternative pathway involving AUXIN BINDING PROTEIN1 (ABP1) has been proposed to regulate clathrin-mediated endocytosis in roots and Rho-like GTPase (ROP)-dependent pavement cell interdigitation in leaves [3, 4]. In this study, we show that ROP6 and its downstream effector RIC1 regulate clathrin association with the plasma membrane for clathrin-mediated endocytosis, as well as for its feedback regulation by auxin. Genetic analysis revealed that ROP6/RIC1 acts downstream of ABP1 to regulate endocytosis. This signaling circuit is also involved in the feedback regulation of PIN-FORMED 1 (PIN1) and PIN2 auxin transporters activity (via its constitutive endocytosis) and corresponding auxin transport-mediated processes, including root gravitropism and leave vascular tissue patterning. Our findings suggest that the signaling module auxin ABP1 ROP6/RIC1 clathrin PIN1/PIN2 is a shared component of the feedback regulation of auxin transport during both root and aerial development