Silicatein, an enzymatic biocatalyst purified from the glassy skeletal elements of a marine sponge, and previously shown capable of catalyzing and structurally directing the hydrolysis and polycondensation of silicon alkoxides to yield silica and silsesquioxanes at low temperature and pressure and neutral pH, is shown to be capable of catalyzing and templating the hydrolysis and subsequent polycondensation of a water-stable alkoxide-like conjugate of titanium to form titanium dioxide. The structure and behavior of the TiO 2 formed through this biocatalytic route, including thermally induced crystal grain growth and phase transformation from anatase to rutile, differ from those of TiO 2 formed from the same precursor via alkali catalysis or thermal pyrolysis. This enzymatic route affords a path to templated synthesis that avoids the high temperatures and extremes of pH typically required for synthesis of metallo-oxanes from the corresponding alkoxide-like precursors, and thus provides access to a new and potentially useful parameter space of structures and properties. The proteins may also be nanoscopically structure-directing, as evidenced by the formation of nanocrystallites of anatase, a polymorph usually formed at much higher temperatures. The summation of weak interactions between the protein and mineral may induce this stabilization and thus may afford a new level of nanostructural control, with associated enhancement of selected performance properties.

The molecular mechanisms underlying the biological synthesis of nanostructured mineral/organic composites have long been recognized to offer exciting prospects for materials science.[1±8] In addition to their benign conditions for synthesis (including neutral pH, low temperature, low pressure, and the absence of caustic chemicals), these mechanisms often reveal a precision of nanostructural control not yet achievable in anthropogenic syntheses. Investigations into such mechanisms have shown that protein filaments occluded within the silica skeletal elements of a marine sponge consist of structure-directing enzymes capable of catalyzing, in vitro, the hydrolysis and polycondensation of molecular precursors of silica, silsesquioxanes, [5,9±11] and titania. [12] We show here that these protein filaments are not only capable of the hydrolysis and polycondensation of a gallium oxide molecular precursor to yield (depending on the reaction conditions) either gallium oxo-hydroxide (GaOOH) or spinel gallium oxide (c-Ga 2 O 3 , a gassensing semiconductor) at room temperature, but also to direct their resulting structures. This control is seen in the defined orientation of nanocrystals with respect to the surface of the protein, suggesting that structural determinants on the surface of the protein catalyze the formation of the c-Ga 2 O 3 polymorph at low temperatures and may direct its crystallographic orientation. These results demonstrate the feasibility of a low-temperature catalytic route to the synthesis and COMMUNICATIONS 314

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Phosphatidylinositol 3-kinase (PI3K) has been implicated in synaptic plasticity and other neural functions in the brain. However, the role of individual PI3K isoforms in the brain is unclear. We investigated the role of PI3Kγ in hippocampal-dependent synaptic plasticity and cognitive functions. We found that PI3Kγ has a crucial and specific role in NMDA receptor (NMDAR)-mediated synaptic plasticity at mouse Schaffer collateral-commissural synapses. Both genetic deletion and pharmacological inhibition of PI3Kγ disrupted NMDAR long-term depression (LTD) while leaving other forms of synaptic plasticity intact. Accompanying this physiological deficit, the impairment of NMDAR LTD by PI3Kγ blockade was specifically correlated with deficits in behavioral flexibility. These findings suggest that a specific PI3K isoform, PI3Kγ, is critical for NMDAR LTD and some forms of cognitive function. Thus, individual isoforms of PI3Ks may have distinct roles in different types of synaptic plasticity and may therefore influence various kinds of behavior.

This paper considers neural signal processing applied to extracellular recordings, in particular, unsupervised action potential detection at a low signal-to-noise ratio. It adopts the basic framework of the multiresolution Teager energy operator (MTEO) detector, but presents important new results including a significantly improved MTEO detector with some mathematical analyses, a new alignment technique with its effects on the whole spike sorting system, and a variety of experimental results. Specifically, the new MTEO detector employs smoothing windows normalized by noise power derived from mathematical analyses and has an improved complexity by utilizing the sampling rate. Experimental results prove that this detector achieves higher detection ratios at a fixed false alarm ratio than the TEO detector and the discrete wavelet transform detector. We also propose a method that improves the action potential alignment performance. Observing that the extreme points of the MTEO output are more robust to the background noise than those of the action potentials, we use the MTEO output for action potential alignment. This brings not only noticeable improvement in alignment performance but also quite favorable influence over the classification performance. Accordingly, the proposed detector improves the performance of the whole spike sorting system. We verified the improvement using various modeled neural signals and some real neural recordings.

Adeno-associated virus (AAV) vectors can deliver transgenes to diverse cell types and are therefore useful for basic research and gene therapy. Although AAV has many advantages over other viral vectors, its relatively small packaging capacity limits its use for delivering large genes. The available transgene size is further limited by the existence of additional elements in the expression cassette without which the gene expression level becomes much lower. By using alternative combinations of shorter elements, we generated a series of AAV expression cassettes and systematically evaluated their expression efficiency in neurons to maximize the transgene size available within the AAV packaging capacity while not compromising the transgene expression. We found that the newly developed smaller expression cassette shows comparable expression efficiency with an efficient vector generally used for strong gene expression. This new expression cassette will allow us to package larger transgenes without compromising expression efficiency.

Newborn neurons in the subgranular zone (SGZ) of the hippocampus incorporate into the dentate gyrus and mature. Numerous studies have focused on hippocampal neurogenesis because of its importance in learning and memory. However, it is largely unknown whether hippocampal neurogenesis is involved in memory extinction per se. Here, we sought to examine the possibility that hippocampal neurogenesis may play a critical role in the formation and extinction of hippocampus-dependent contextual fear memory. By methylazoxymethanol acetate (MAM) or gamma-ray irradiation, hippocampal neurogenesis was impaired in adult mice. Under our experimental conditions, only a severe impairment of hippocampal neurogenesis inhibited the formation of contextual fear memory. However, the extinction of contextual fear memory was not affected. These results suggest that although adult newborn neurons contribute to contextual fear memory, they may not be involved in the extinction or erasure of hippocampus-dependent contextual fear memory.

S100A8 and S100A9 (S100A8/A9) are low-molecular weight members of the S100 family of calcium-binding proteins. Recent studies have reported S100A8/A9 promote tumorigenesis. We have previously reported that S100A8/A9 is mostly expressed in stromal cells and inflammatory cells between gastric tumor cells. However, the role of environmental S100A8/A9 in gastric cancer has not been defined. We observed in the present study the effect of S100A8/A9 on migration and invasion of gastric cancer cells. S100A8/ A9 treatment increased migration and invasionat lower concentrations that did not affect cell proliferation and cell viability. S100A8/A9 caused activation of p38 mitogenactivated protein kinase (MAPK) and nuclear factor-κB (NF-κB). The phosphorylation of p38 MAPK was not affected by the NF-κB inhibitor Bay whereas activation of NF-κB was blocked by p38 MAPK inhibitor SB203580, indicating that S100A8/A9-induced NF-κB activation is mediated by phosphorylation of p38 MAPK. S100A8/A9-induced cell migration and invasion was inhibited by SB203580 and Bay, suggesting that activation of p38 MAPK and NF-κB is involved in the S100A8/A9 induced cell migration and invasion. S100A8/A9 caused an increase in matrix metalloproteinase 2 (MMP2) and MMP12 expression, which were inhibited by SB203580 and Bay. S100A8/A9-induced cell migration and invasion was inhibited by MMP2 siRNA and MMP12 siRNA, indicating that MMP2 and MMP12 is related to the S100A8/A9 induced cell migration and invasion. Taken together, these results suggest that S100A8/A9 promotes cell migration and invasion through p38 MAPKdependent NF-κB activation leading to an increase of MMP2 and MMP12 in gastric cancer.