The tumour suppressor Hippo acts with the NDR kinases in dendritic tiling and maintenance

Precise patterning of dendritic fields is essential for neuronal circuit formation and function, but how neurons establish and maintain their dendritic fields during development is poorly understood. In Drosophila class IV dendritic arborization neurons, dendritic tiling, which allows for the complete but non-overlapping coverage of the dendritic fields, is established through a 'like-repels-like' behaviour of dendrites mediated by Tricornered (Trc), one of two NDR (nuclear Dbf2-related) family kinases in Drosophila. Here we report that the other NDR family kinase, the tumour suppressor Warts/Lats (Wts), regulates the maintenance of dendrites; in wts mutants, dendrites initially tile the body wall normally, but progressively lose branches at later larval stages, whereas the axon shows no obvious defects. We further provide biochemical and genetic evidence for the tumour suppressor kinase Hippo (Hpo) as an upstream regulator of Wts and Trc for dendrite maintenance and tiling, respectively, thereby revealing important functions of tumour suppressor genes of the Hpo signalling pathway in dendrite morphogenesis.     

A proteasomal ATPase subunit recognizes the polyubiquitin degradation signal

The 26S proteasome is the chief site of regulatory protein turnover in eukaryotic cells. It comprises one 20S catalytic complex (composed of four stacked rings of seven members) and two axially positioned 19S regulatory complexes (each containing about 18 subunits) that control substrate access to the catalytic chamber. In most cases, targeting to the 26S proteasome depends on tagging of the substrate with a specific type of polyubiquitin chain. Recognition of this signal is followed by substrate unfolding and translocation, which are presumably catalysed by one or more of six distinct AAA ATPases located in the base-a ring-like 19S subdomain that abuts the axial pore of the 20S complex and exhibits chaperone activity in vitro. Despite the importance of polyubiquitin chain recognition in proteasome function, the site of this signal's interaction with the 19S complex has not been identified previously. Here we use crosslinking to a reactive polyubiquitin chain to show that a specific ATPase subunit, S6' (also known as Rpt5), contacts the bound chain. The interaction of this signal with 26S proteasomes is modulated by ATP hydrolysis. Our results suggest that productive recognition of the proteolytic signal, as well as proteasome assembly and substrate unfolding, are ATP-dependent events.     

Dynamic fracture by large extraterrestrial impacts as the origin of shatter cones

A large impact by a comet or meteorite releases an enormous amount of energy, which evaporates, melts and fractures the surrounding rocks. Distinctive features of such impacts are 'shatter cones', deformed rocks characterized by hierarchical striated features. Although such features have been used for decades as unequivocal fingerprints of large-body impacts, the process by which shatter cones form has remained enigmatic. Here we show that the distinctive shatter-cone striations naturally result from nonlinear waves (front waves) that propagate along a fracture front. This explains the observed systematic increase of striation angles with the distance from the impact. Shatter-cone networks, typically spanning many scales, can be understood as hierarchical bifurcations of the fracture front, which is generated by the immense energy flux carried by the initial, impact-generated, shock waves. Our quantitative predictions based on this theory are supported by field measurements at the Kentland and Vredefort impact sites. These measurements indicate that shatter cones near to the impact site were formed by fractures propagating at nearly the Rayleigh wave speed of the host rocks, whereas the furthest shatter cones observed (about 40 km from the impact site) were formed by fronts moving more slowly. These results provide insight into impact dynamics as well as dissipative mechanisms in solids subjected to sudden, extremely intense fluxes of energy.     

Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal-dominant central nervous system white-matter disease with variable clinical presentations, including personality and behavioral changes, dementia, depression, parkinsonism, seizures and other phenotypes. We combined genome-wide linkage analysis with exome sequencing and identified 14 different mutations affecting the tyrosine kinase domain of the colony stimulating factor 1 receptor (encoded by CSF1R) in 14 families with HDLS. In one kindred, we confirmed the de novo occurrence of the mutation. Follow-up sequencing identified an additional CSF1R mutation in an individual diagnosed with corticobasal syndrome. In vitro, CSF-1 stimulation resulted in rapid autophosphorylation of selected tyrosine residues in the kinase domain of wild-type but not mutant CSF1R, suggesting that HDLS may result from partial loss of CSF1R function. As CSF1R is a crucial mediator of microglial proliferation and differentiation in the brain, our findings suggest an important role for microglial dysfunction in HDLS pathogenesis.     

一种基于可靠性的设备顺序预防性维护模型

等周期预防性维护策略不可避免地会使设备的可靠性随着役龄及维护次数的增加而逐步降低．为此,结合役龄递减因子和故障率递增因子的优点,通过引入基于两类调整因子的混合式故障率演化规则,建立了基于设备可靠性的顺序预防性维护优化模型,并以威布尔分布为例,利用蒙特卡罗仿真方法对其进行了优化．结果显示,该模型符合设备的实际维护情况,可为设备的维护决策提供有力的支持．     

Radio transmitter attachment for chukars

Thirty-seven chukars ( Alectoris chukar ), fitted with conventional poncho-type radio transmitters, were released on Antelope Island in Utah's Great Salt Lake. Twenty-seven removed their radios, averaging three days after release. The remaining 10 died from predation (average 15 days). Twenty-two chukars with pleated and six with harness ponchos were then released. Five of the pleated ponchos were removed (average four days), and 17 resulted in mortality (average two days). All six harness poncho-equipped birds were dead the following day. A consequential laboratory study comparing various attachment methods (conventional, pleated, harness, and ""irreversible"" flange poncho vs. bellystrap and wingstrap backpack) favored the wingstrap backpack. The effectiveness of 30 conventional ponchos and 30 wingstrap backpacks was compared on game farm chukars. Twenty-nine removed their ponchos within one day. One remained attached throughout the 30-day trial. All of the wingstrap backpacks remained attached with no apparent problems.