Two distinct modes of guidance signalling during collective migration of border cells

Although directed migration is a feature of both individual cells and cell groups, guided migration has been studied most extensively for single cells in simple environments. Collective guidance of cell groups remains poorly understood, despite its relevance for development and metastasis. Neural crest cells and neuronal precursors migrate as loosely organized streams of individual cells, whereas cells of the fish lateral line, Drosophila tracheal tubes and border-cell clusters migrate as more coherent groups. Here we use Drosophila border cells to examine how collective guidance is performed. We report that border cells migrate in two phases using distinct mechanisms. Genetic analysis combined with live imaging shows that polarized cell behaviour is critical for the initial phase of migration, whereas dynamic collective behaviour dominates later. PDGF- and VEGF-related receptor and epidermal growth factor receptor act in both phases, but use different effector pathways in each. The myoblast city (Mbc, also known as DOCK180) and engulfment and cell motility (ELMO, also known as Ced-12) pathway is required for the early phase, in which guidance depends on subcellular localization of signalling within a leading cell. During the later phase, mitogen-activated protein kinase and phospholipase Cgamma are used redundantly, and we find that the cluster makes use of the difference in signal levels between cells to guide migration. Thus, information processing at the multicellular level is used to guide collective behaviour of a cell group.     

行星着陆——推进下降过程的建模与控制(英文)

登陆火星或月球时,释放降落伞后进入推进阶段,通过轴向推力倾斜实现水平方向运动,能够与速度矢量(重力)的相反方向一致或与需要的加速度方向保持一致.后一种策略能实现精确着陆,在该策略下,倾斜角(俯仰角和偏转角)与水平加速度成正比.这种策略并未采用以水平加速度为姿态控制目标的递阶导航与控制方案,而是基于角加速度对位置作用的四阶动力学特性设计了一个独特的控制系统.除去倾斜角的非线性因素(垂直制动规定的轴向推力)后,系统综合动力学方程能够实现(准)输入-状态线性化.论文同时表明:一方面,基于参考轨迹(倾斜角和位置)的控制器设计仅能实现部分输入-状态线性化;另一方面,系统的内部稳定性可以证明.即使存在不可镇定的外部干扰动力学模态时,仍能确保系统稳定性.蒙特卡洛仿真验证了闭环控制策略的有效性.     

四点弯曲试验条件下页岩的声发射特性

利用PXWAE型声发射系统进行了四点弯曲试验条件下页岩的声发射试验研究,试验中记录了岩样所受的最大弯曲应力、弯曲应变、声发射事件数、声发射能量等多个参数。研究发现,垂直页岩层理施加荷载时,在四点弯曲试验条件下其凯塞效应是存在的,凯塞点可以直接通过应力与累计声发射事件数曲线得出;但受自身水平层理结构及局部破坏的影响,应变在受载过程中会发生松弛现象,不易直接由应变-声发射试验曲线判断出岩石的凯塞点,必须结合其它试验数据以及岩样的最终破坏形态综合判断。弯曲应力状态下岩石的声发射特性研究对于利用声发射技术进行矿区顶板或隔层的稳定性监测具有一定的工程指导意义。     

Cellular factors modulating the mechanism of tau protein aggregation

Pathological accumulation of the microtubule-associated protein tau, in the form of neurofibrillary tangles, is a major hallmark of Alzheimer’s disease, the most prevalent neurodegenerative condition worldwide. In addition to Alzheimer’s disease, a number of neurodegenerative diseases, called tauopathies, are characterized by the accumulation of aggregated tau in a variety of brain regions. While tau normally plays an important role in stabilizing the microtubule network of the cytoskeleton, its dissociation from microtubules and eventual aggregation into pathological deposits is an area of intense focus for therapeutic development. Here we discuss the known cellular factors that affect tau aggregation, from post-translational modifications to molecular chaperones.     

Inactivation of the p53 pathway in retinoblastoma

Most human tumours have genetic mutations in their Rb and p53 pathways, but retinoblastoma is thought to be an exception. Studies suggest that retinoblastomas, which initiate with mutations in the gene retinoblastoma 1 (RB1), bypass the p53 pathway because they arise from intrinsically death-resistant cells during retinal development. In contrast to this prevailing theory, here we show that the tumour surveillance pathway mediated by Arf, MDM2, MDMX and p53 is activated after loss of RB1 during retinogenesis. RB1-deficient retinoblasts undergo p53-mediated apoptosis and exit the cell cycle. Subsequently, amplification of the MDMX gene and increased expression of MDMX protein are strongly selected for during tumour progression as a mechanism to suppress the p53 response in RB1-deficient retinal cells. Our data provide evidence that the p53 pathway is inactivated in retinoblastoma and that this cancer does not originate from intrinsically death-resistant cells as previously thought. In addition, they support the idea that MDMX is a specific chemotherapeutic target for treating retinoblastoma.