Non-Markovian recovery makes complex networks more resilient against large-scale failures.

Non-Markovian spontaneous recovery processes with a time delay (memory) are ubiquitous in the real world. How does the non-Markovian characteristic affect failure propagation in complex networks? We consider failures due to internal causes at the nodal level and external failures due to an adverse environment, and develop a pair approximation analysis taking into account the two-node correlation. In general, a high failure stationary state can arise, corresponding to large-scale failures that can significantly compromise the functioning of the network. We uncover a striking phenomenon: memory associated with nodal recovery can counter-intuitively make the network more resilient against large-scale failures. In natural systems, the intrinsic non-Markovian characteristic of nodal recovery may thus be one reason for their resilience. In engineering design, incorporating certain non-Markovian features into the network may be beneficial to equipping it with a strong resilient capability to resist catastrophic failures.

PPAR Gamma Coactivator 1 Beta (PGC-1ß) Reduces Mammalian Target of Rapamycin (mTOR) Expression via a SIRT1-Dependent Mechanism in Neurons.

Mammalian target of rapamycin (mTOR) is a key regulator of metabolism, cell growth, and protein synthesis. Since decreased mTOR activity has been found to slow aging in many species, the aim of this study was to examine the activity of mTOR and its phosphorylated form in in vitro and in vivo models mimicking Alzheimer's disease (AD), and investigate the potential pathway of PGC-1ß in regulating mTOR expression. Primary neurons and N2a cells were treated with Aß25-35, while untreated cells served as controls. The expression of mTOR, p-mTOR (Ser2448), and PGC-1ß was determined with Western blotting and RT-PCR assay, and the translocation of mTOR was detected using confocal microscopy. Aß25-35 treatment stimulated the translocation of mTOR from cytoplasm to nucleus, and resulted in elevated expression of mTOR and p-mTOR (Ser2448) and reduced PGC-1ß expression. In addition, overexpression of PGC-1ß was found to decrease mTOR expression. The results of this study demonstrate that Aß increases the expression of mTOR and p-mTOR at the site of Ser2448, and the stimulation of Aß is likely to depend on sirtuin 1, PPARγ, and PGC-1ß pathway in regulating mTOR expression.

[Generation and characterization of the adult neuron-specific ADAM10 knock-out mice].

A disintegrin and metalloproteinase 10 (ADAM10) is a major sheddase for over 30 different membrane proteins and gets involved in such physiological processes and pathogenesis as embryonic development, cell adhesion, signal transduction, immune reaction, cancer, and Alzheimer's disease. Both ADAM10 knock-out mice and the neural progenitor cell-specific ADAM10 knock-out mice having been reported so far died in the embryonic or perinatal stage, respectively, thus resulting in the failure to investigate ADAM10 function in the adult mouse brain. Through a series of tests, we have succeeded in generating and characterizing the CaMKIIα-Cre/ADAM10(loxP/loxP) mice surviving until adulthood by means of crossing ADAM10(loxP/loxP) mice with newly generated CaMKIIα-Cre transgenic mice. PCR analysis of genomic DNAs from different regions of the ADAM10 cKO mouse brain shows that the deleted ADAM10 alleles are mainly found in the cortex and hippocampus. Real-time RT-PCR findings further confirm that ADAM10 mRNAs decrease in the cortex and hippocampus by 55.7% and 60.8%, respectively. Western-blotting analysis demonstrates 63% and 84.8% loss of mature ADAM10 proteins from the cortex and hippocampus. Immunohistochemical tests show that there is significantly less ADAM10- positive staining in the cortical and hippocampal neurons but not gliocytes of ADAM10 cKO mice compared with control mice. In summary, we established the adult neuron-specific ADAM10 knock-out (cKO) mice for the first time, which prevented ADAM10(-/-) mice from the embryonic and perinatal mortality and laid a firm foundation for the further study of ADAM10 function in the brain of adult mice in vivo.