Deleted in colorectal carcinoma suppresses metastasis in p53-deficient mammary tumours

Since its discovery in the early 1990s the deleted in colorectal cancer (DCC) gene, located on chromosome 18q21, has been proposed as a tumour suppressor gene as its loss is implicated in the majority of advanced colorectal and many other cancers. DCC belongs to the family of netrin 1 receptors, which function as dependence receptors as they control survival or apoptosis depending on ligand binding. However, the role of DCC as a tumour suppressor remains controversial because of the rarity of DCC-specific mutations and the presence of other tumour suppressor genes in the same chromosomal region. Here we show that in a mouse model of mammary carcinoma based on somatic inactivation of p53, additional loss of DCC promotes metastasis formation without affecting the primary tumour phenotype. Furthermore, we demonstrate that in cell cultures derived from p53-deficient mouse mammary tumours DCC expression controls netrin-1-dependent cell survival, providing a mechanistic basis for the enhanced metastatic capacity of tumour cells lacking DCC. Consistent with this idea, in vivo tumour-cell survival is enhanced by DCC loss. Together, our data support the function of DCC as a context-dependent tumour suppressor that limits survival of disseminated tumour cells.     

Phase transitions in the assembly of multivalent signalling proteins

Cells are organized on length scales ranging from ?ngstr?m to micrometres. However, the mechanisms by which ?ngstr?m-scale molecular properties are translated to micrometre-scale macroscopic properties are not well understood. Here we show that interactions between diverse synthetic, multivalent macromolecules (including multi-domain proteins and RNA) produce sharp liquid-liquid-demixing phase separations, generating micrometre-sized liquid droplets in aqueous solution. This macroscopic transition corresponds to a molecular transition between small complexes and large, dynamic supramolecular polymers. The concentrations needed for phase transition are directly related to the valency of the interacting species. In the case of the actin-regulatory protein called neural Wiskott-Aldrich syndrome protein (N-WASP) interacting with its established biological partners NCK and phosphorylated nephrin, the phase transition corresponds to a sharp increase in activity towards an actin nucleation factor, the Arp2/3 complex. The transition is governed by the degree of phosphorylation of nephrin, explaining how this property of the system can be controlled to regulatory effect by kinases. The widespread occurrence of multivalent systems suggests that phase transitions may be used to spatially organize and biochemically regulate information throughout biology.     

岩板变形破坏过程加载装置设计及试验验证

浅埋采空区顶板变形破坏过程与灾变机理研究,是目前下伏采空区建(构)筑物工程实践中急待解决的难题。针对国内外在岩板变形破坏试验中存在的不足,自行研发了能够进行岩石类材料矩形板弯曲试验的加载装置。利用MTS岩石力学试验机和研发的加载装置,对单层岩板断裂铰接成拱的过程及其失稳机理进行了分析,并对双层组合岩板进行了变形破坏过程的试验研究。试验结果表明:随着施加荷载的不断增大,单层岩板梁式断裂后铰接形成拱形结构,并在铰接点产生水平反力。双层组合岩板的上层板存在梁式断裂、拱形破坏和板式断裂破坏3种破坏模式。单层岩板和双层岩板的荷载-位移全过程曲线,均存在4个明显的力学响应阶段,并由该曲线分析了岩拱结构形成过程及其失稳的特征。     

Deep origin and hot melting of an Archaean orogenic peridotite massif in Norway

The buoyancy and strength of sub-continental lithospheric mantle is thought to protect the oldest continental crust (cratons) from destruction by plate tectonic processes. The exact origin of the lithosphere below cratons is controversial, but seems clearly to be a residue remaining after the extraction of large amounts of melt. Models to explain highly melt-depleted but garnet-bearing rock compositions require multi-stage processes with garnet and clinopyroxene possibly of secondary origin. Here we report on orogenic peridotites (fragments of cratonic mantle incorporated into the crust during continent-continent plate collision) from Otr?y, western Norway. We show that the peridotites underwent extensive melting during upwelling from depths of 350 kilometres or more, forming a garnet-bearing cratonic root in a single melting event. These peridotites appear to be the residue after Archaean aluminium depleted komatiite magmatism.