Chronic spinal cord injury (SCI) is a formidable hurdle that prevents a large number of injured axons from crossing the lesion, particularly the corticospinal tract (CST). This study shows that Pten deletion in the adult mouse cortex enhances compensatory sprouting of uninjured CST axons. Furthermore, forced upregulation of mammalian target of rapamycin (mTOR) initiated either 1 month or 1 year after injury promoted regeneration of CST axons.Ourresultsindicatethatbothdevelopmentalandinjury-inducedmTORdownregulationincorticospinalmotorneuronscanbereversedinadults. Modulating neuronal mTOR activity is a potential strategy for axon regeneration after chronic SCI.

SUMMARYBrefeldin A (BFA) is a useful tool for studying protein trafficking and identifying organelles in the plant secretory and endocytic pathways. At low concentrations (5-10 lg ml )1 ), BFA caused both the Golgi apparatus and trans-Golgi network (TGN), an early endosome (EE) equivalent in plant cells, to form visible aggregates in transgenic tobacco BY-2 cells. Here we show that these BFA-induced aggregates from the Golgi apparatus and TGN are morphologically and functionally distinct in plant cells. Confocal immunofluorescent and immunogold electron microscope (EM) studies demonstrated that BFA-induced Golgi-and TGN-derived aggregates are physically distinct from each other. In addition, the internalized endosomal marker FM4-64 co-localized with the TGN-derived aggregates but not with the Golgi aggregates. In the presence of the endocytosis inhibitor tyrphostin A23, which acts in a dose-and time-dependent manner, SCAMP1 (secretory carrier membrane protein 1) and FM4-64 are mostly excluded from the SYP61-positive BFA-induced TGN aggregates, indicating that homotypic fusion of the TGN rather than de novo endocytic trafficking is important for the formation of TGN/EE-derived BFA-induced aggregates. As the TGN also serves as an EE, continuously receiving materials from the plasma membrane, our data support the notion that the secretory Golgi organelle is distinct from the endocytic TGN/EE in terms of its response to BFA treatment in plant cells. Thus, the Golgi and TGN are probably functionally distinct organelles in plants.

The Uncertain Capacitated Arc Routing Problem (UCARP) is a challenging problem where the demands of tasks, the costs of edges, and the presence of tasks and edges are uncertain. The objective of this problem is to find a robust optimal solution for a finite set of possible scenarios. In this paper, we propose a novel robust optimization approach, called an Estimation of Distribution Algorithm with Stochastic Local Search (EDASLS), to tackle this problem. The proposed method integrates an estimation of distribution algorithm with a novel two phase stochastic local search procedure to minimize the maximal total cost over a set of different scenarios. The stochastic local search procedure avoids excessive fitness evaluations of unpromising moves in local search. Our experimental results on two sets of benchmark problems (a total of 55 problem instances) showed that the proposed approach outperformed existing state-of-the-art algorithms. in 2010, and is currently working towards her Ph.D. degree. Her current research interests include memetic algorithm and other metaheuristics for solving capacitated arc routing problems.1089-778X (c)

Peripheral nerve regeneration and functional recovery remain a significant clinical challenge. Biomaterials that can regulate biological behavior of Schwann cell (SC) and promote neural cell differentiation are beneficial for nerve regeneration and functional recovery. Graphene oxide (GO), as a bioactive nanomaterial, has attracted great attention in biomedical applications. In this study, the possibility of combining the excellent physicochemical properties of GO with nanofiber to develop a bioactive scaffold for nerve regeneration were explored. Briefly, GO was coated on the ApF/PLCL scaffolds. To demonstrate the potentials of this platform, in vitro and in vivo studies toward nerve regeneration were carried out. In vitro, GO-coated scaffolds could enhance SC biological behaviors including migration, proliferation, and myelination. The secretions from SCs cultured on GO-ApF/PLCL scaffolds could induce PC12 cells differentiation. Furthermore, GO-coated nanofibrous scaffolds proved to up-regulate focal adhesion kinase (FAK) expression of PC12 cell. In vivo, GO-ApF/PLCL nerve conduits could successfully repair a 10 mm sciatic nerve defect. These findings suggest that GO-based scaffolds efficiently modulate cell functions and promote nerve regeneration, indicating their potential for nerve regeneration applications.

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