SUMMARY IDH1 and IDH2 mutations occur frequently in gliomas and acute myeloid leukemia, leading to simultaneous loss and gain of activities in the production of α-ketoglutarate (α-KG) and 2-hydroxyglutarate (2-HG), respectively. Here we demonstrate that 2-HG is a competitive inhibitor of multiple α-KG-dependent dioxygenases, including histone demethylases and the TET family of 5-methlycytosine (5mC) hydroxylases. 2-HG occupies the same space as α-KG does in the active site of histone demethylases. Ectopic expression of tumor-derived IDH1 and IDH2 mutants inhibits histone demethylation and 5mC hydroxylation. In glioma, IDH1 mutations are associated with increased histone methylation and decreased 5-hydroxylmethylcytosine (5hmC). Hence, tumor-derived IDH1 and IDH2 mutations reduce α-KG and accumulate an α-KG antagonist, 2-HG, leading to genome-wide histone and DNA methylation alterations.

SCF complexes are the largest family of E3 ubiquitin-protein ligases and mediate the ubiquitination of diverse regulatory and signalling proteins. Here we present the crystal structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF complex, which shows that Cul1 is an elongated protein that consists of a long stalk and a globular domain. The globular domain binds the RING finger protein Rbx1 through an intermolecular beta-sheet, forming a two-subunit catalytic core that recruits the ubiquitin-conjugating enzyme. The long stalk, which consists of three repeats of a novel five-helix motif, binds the Skp1-F boxSkp2 protein substrate-recognition complex at its tip. Cul1 serves as a rigid scaffold that organizes the Skp1-F boxSkp2 and Rbx1 subunits, holding them over 100 A apart. The structure suggests that Cul1 may contribute to catalysis through the positioning of the substrate and the ubiquitin-conjugating enzyme, and this model is supported by Cul1 mutations designed to eliminate the rigidity of the scaffold.

Radio frequency (RF) energy transfer and harvesting techniques have recently become alternative methods to power the next generation wireless networks. As this emerging technology enables proactive energy replenishment of wireless devices, it is advantageous in supporting applications with quality of service (QoS) requirements. In this paper, we present a comprehensive literature review on the research progresses in wireless networks with RF energy harvesting capability, referred to as RF energy harvesting networks (RF-EHNs). First, we present an overview of the RF-EHNs including system architecture, RF energy harvesting techniques and existing applications. Then, we present the background in circuit design as well as the state-of-the-art circuitry implementations, and review the communication protocols specially designed for RF-EHNs. We also explore various key design issues in the development of RF-EHNs according to the network types, i.e., single-hop networks, multi-antenna networks, relay networks, and cognitive radio networks. Finally, we envision some open research directions.Index Terms-RF energy harvesting, simultaneous wireless information and power transfer (SWIPT), receiver operation policy, beamforming, communication protocols, RF-powered Cognitive radio network.1553-877X (c) 2 transmission. Traditionally, free-space beaming and antennas with large apertures are used to overcome propagation loss for large power transfer. For example, in 1960's, the authors in [15] demonstrate a small helicopter hovering at a height of 50 feet, powered by an RF source with a DC power supply of 270W operating on 2.45GHz on the ground. In [16], the authors demonstrate a space-to-earth power transfer system using gigantic transmit antenna arrays at a satellite and receive antenna arrays at a ground station. For transmit power of 2.7GW, the power transfer efficiency is estimated to be 45% over a transfer distance of 36000km. During the past decade, with the development in RF energy harvesting circuit, low power transfer for powering mobile terminals in wireless communication systems began to attract increasing attention [17], [18]. The authors in [17] propose a network architecture for RF charging stations, overlaying with an uplink cellular network. In [18], a harvest-then-transmit protocol is introduced for power transfer in wireless broadcast system. Moreover, various modern beamforming techniques are employed to improve power transfer efficiency [18]-[20] for mobile applications.It is until recently that the dual use of RF signals for delivering energy as well as for transporting information has been advocated [21], [22]. Simultaneous wireless information and power transfer (SWIPT) [23] is proposed for delivering RF energy, usually in a low power region (e.g., for sensor networks). SWIPT provides the advantage of delivering controllable and efficient on-demand wireless information and energy concurrently, which offers a low-cost option for sustainable operations of wireless systems without hardware modification on the ...

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