Lu Liu

Cyclin-dependent kinase 5 has been implicated in Alzheimer's disease pathogenesis. Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A p25/cdk5 responsive region containing multiple sites for signal transducer and activator of transcription was identified in the BACE1 promoter. STAT3 interacts with the BACE1 promoter, and p25-overexpressing mice had elevated levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels. Furthermore, mice with a targeted mutation in the STAT3 cdk5 responsive site had lower levels of BACE1. Increased BACE levels in p25 overexpressing mice correlated with enhanced amyloidogenic processing that could be reversed by a cdk5 inhibitor. These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis

Smart grids are rolling out internationally, with the United States nearing completion of a significant USD4-plus-billion federal program funded under the American Recovery and Reinvestment Act. The emergence of smart grids is widespread across developed countries. Multiple approaches to analyzing the benefits of smart grids have emerged. The goals of this white paper are to review these approaches and analyze examples of each to highlight their differences, advantages, and disadvantages. This work was conducted under the auspices of a joint U.S.-China research effort, the Climate Change Working Group Implementation Plan, Smart Grid. We present comparative benefits assessments of smart grid demonstrations in the U.S. and China along with a BA of a pilot project in Europe. In the U.S., we assess projects at two sites: the University of California, Irvine campus, which consists of two distinct demonstrations: Southern California Edison’s Irvine Smart Grid Demonstration Project and the UCI campus itself; and the Navy Yard area in Philadelphia, which has been repurposed as a mixed commercial-industrial, and possibly residential, development. In China, we cover several smart-grid aspects of the Sino-Singapore Tianjin Eco-city and the Shenzhen Bay Technology and Ecology City. In Europe, we look at a BA of a pilot smart grid project in the Malagrotta area west of Rome, Italy, contributed by the Joint Research Centre of the European Commission. The Irvine sub-project BAs use the U.S. Department of Energy Smart Grid Computational Tool, which is built on methods developed by the Electric Power Research Institute. The TEC sub-project BAs apply Smart Grid Multi-Criteria Analysis developed by the State Grid Corporation of China based on the analytic hierarchy process with fuzzy logic. The B-TEC and TNY sub-project BAs are evaluated using new approaches developed by those project teams. JRC has adopted an approach similar to EPRI’s but tailored to the Malagrotta distribution grid.

Let K denote prefix-free Kolmogorov complexity, and let $K^A$ denote it relative to an oracle A. We show that for any n, $K^{\emptyset ^{(n)}}$ is definable purely in terms of the unrelativized notion K. It was already known that 2-randomness is definable in terms of K (and plain complexity C) as those reals which infinitely often have maximal complexity. We can use our characterization to show that n-randomness is definable purely in terms of K. To do this we extend a certain “limsup” formula from the literature, and apply Symmetry of Information. This extension entails a novel use of semilow sets, and a more precise analysis of the complexity of $\Delta _2^0$ sets of minimal descriptions.

A series of derivatives of the known thromboxane A2 prostanoid receptor antagonists, 3-sulfonamido)-5,6,7,8-tetrahydronaphthalen-1-yl)propanoic acid and 3-sulfonamido)ethyl)phenyl) propanoic acid, were synthesized in which the carboxylic acid functional group was replaced with substituted cyclopentane-1,3-dione bioisosteres. Characterization of these molecules led to the discovery of remarkably potent new analogues, some of which were considerably more active than the corresponding parent carboxylic acid compounds. Depending on the choice of the C2 substituent of the CPD unit, these new derivatives can produce either a reversible or an apparent irreversible inhibition of the human TP receptor. Given the potency and the long-lasting inhibition of TP receptor signaling, these novel antagonists may comprise promising leads for the development of antithromboxane therapies.

© 2016 The Author.Nucleotide sugar transport across Golgi membranes is essential for the luminal biosynthesis of glycan structures. Here we identify GDP-fucose transporter 1, an Arabidopsis nucleotide sugar transporter that translocates GDP-L-fucose into the Golgi lumen. Using proteo-liposome-based transport assays, we show that GFT preferentially transports GDP-L-fucose over other nucleotide sugars in vitro, while GFT1-silenced plants are almost devoid of L-fucose in cell wall-derived xyloglucan and rhamnogalacturonan II. Furthermore, these lines display reduced L-fucose content in N-glycan structures accompanied by severe developmental growth defects. We conclude that GFT1 is the major nucleotide sugar transporter for import of GDP-L-fucose into the Golgi and is required for proper plant growth and development.

The thin set theorem for n-tuples and k colors states that every k-coloring of $[\mathbb {N}]^n$ admits an infinite set of integers H such that $[H]^n$ avoids at least one color. In this paper, we study the combinatorial weakness of the thin set theorem in reverse mathematics by proving neither $\operatorname {\mathrm {\sf {TS}}}^n_k$, nor the free set theorem imply the Erdős–Moser theorem whenever k is sufficiently large. Given a problem $\mathsf {P}$, a computable instance of $\mathsf {P}$ is universal iff its solution computes a solution of any other computable $\mathsf {P}$ -instance. It has been established that most of Ramsey-type problems do not have a universal instance, but the case of Erdős–Moser theorem remained open so far. We prove that Erdős–Moser theorem does not admit a universal instance.

© 2016 American Society of Plant Biologists. All rights reserved.Calcium/calmodulin-dependent protein kinase has been shown to play an important role in abscisic acid -induced antioxidant defense and enhance the tolerance of plants to drought stress. However, its downstream molecular events are poorly understood. Here, we identify a NAC transcription factor, ZmNAC84, in maize, which physically interacts with ZmCCaMK in vitro and in vivo. ZmNAC84 displays a partially overlapping expression pattern with ZmCCaMK after ABA treatment, and H2O2 is required for ABA-induced ZmNAC84expression. Functional analysis reveals that ZmNAC84 is essential for ABA-induced antioxidant defense in a ZmCCaMK-dependent manner. Furthermore, ZmCCaMK directly phosphorylates Ser-113 of ZmNAC84 in vitro, and Ser-113 is essential for the ABA-induced stimulation of antioxidant defense by ZmCCaMK. Moreover, overexpression of ZmNAC84 in tobacco can improve drought tolerance and alleviate drought-induced oxidative damage of transgenic plants. These results define a mechanism for ZmCCaMK function in ABA-induced antioxidant defense, where ABA-produced H2O2 first induces expression of ZmCCaMK and ZmNAC84 and activates ZmCCaMK. Subsequently, the activated ZmCCaMK phosphorylates ZmNAC84 at Ser-113, thereby inducing antioxidant defense by activating downstream genes.