The heme-p53 interaction: Linking iron metabolism to p53 signaling and tumorigenesis

Recently, we reported that heme binds to tumor suppressor p53 protein (TP53, best known as p53) and promotes its nuclear export and cytosolic degradation, whereas iron chelation stabilizes p53 protein and suppresses tumors in a p53-dependent manner. This not only provides mechanistic insights into tumorigenesis associated with iron excess, but also helps guide the administration of chemotherapy based on iron deprivation in the clinic

Iron Metabolism Regulates p53 Signaling through Direct Heme-p53 Interaction and Modulation of p53 Localization, Stability, and Function

Iron excess is closely associated with tumorigenesis in multiple types of human cancers, with underlying mechanisms yet unclear. Recently, iron deprivation has emerged as a major strategy for chemotherapy, but it exerts tumor suppression only on select human malignancies. Here, we report that the tumor suppressor protein p53 is downregulated during iron excess. Strikingly, the iron polyporphyrin heme binds to p53 protein, interferes with p53-DNA interactions, and triggers both nuclear export and cytosolic degradation of p53. Moreover, in a tumorigenicity assay, iron deprivation suppressed wild-type p53-dependent tumor growth, suggesting that upregulation of wild-type p53 signaling underlies the selective efficacy of iron deprivation. Our findings thus identify a direct link between iron/heme homeostasis and the regulation of p53 signaling, which not only provides mechanistic insights into iron-excess-associated tumorigenesis but may also help predict and improve outcomes in iron-deprivation-based chemotherapy

Modulation of host cell processes by T3SS effectors

Two of the enteric Escherichia coli pathotypes-enteropathogenic E. coli (EPEC) and enterohaemorrhagic E. coli (EHEC)-have a conserved type 3 secretion system which is essential for virulence. The T3SS is used to translocate between 25 and 50 bacterial proteins directly into the host cytosol where they manipulate a variety of host cell processes to establish a successful infection. In this chapter, we discuss effectors from EPEC/EHEC in the context of the host proteins and processes that they target-the actin cytoskeleton, small guanosine triphosphatases and innate immune signalling pathways that regulate inflammation and cell death. Many of these translocated proteins have been extensively characterised, which has helped obtain insights into the mechanisms of pathogenesis of these bacteria and also understand the host pathways they target in more detail. With increasing knowledge of the positive and negative regulation of host signalling pathways by different effectors, a future challenge is to investigate how the specific effector repertoire of each strain cooperates over the course of an infection

On-Orbit Calibration for Spaceborne Line Array Camera and LiDAR

For a multi-mode Earth observation satellite carrying a line array camera and a multi-beam line array LiDAR, the relative installation attitude of the two sensors is of great significance. In this paper, we propose an on-orbit calibration method for the relative installation attitude of the camera and the LiDAR with no need for the calibration field and additional satellite attitude maneuvers. Firstly, the on-orbit joint calibration model of the relative installation attitude of the two sensors is established. However, there may exist a multi-solution problem in the solving of the above model constrained by non-ground control points. Thus, an alternate iterative method by solving the pseudo-absolute attitude matrix of each sensor in turn is proposed. The numerical validation and simulation experiments results show that the relative positioning error of the line array camera and the LiDAR in the horizontal direction of the ground can be limited to 0.8 m after correction by the method in this paper

Lithium storage in commercial MoS2 in different potential ranges

Transition metal sulfides are regarded as another type of high-performance anode materials following the transition metal oxides for lithium ion batteries. However, the lithium storage mechanisms of these sulfides are complicated. This work is intended to evaluate the electrochemical performances of molybdenum disulfide (MOS2)and find out its lithium storage mechanism at different lithium insertion stages. It is found that although the MOS2 shows excellent cycling stability in different voltage ranges, its structural transition is irreversible in the initial cycling. In contrast to the traditional beliefs, metallic Mo is found inert and Li2S/S is the redox couple in a deeply discharged MOS2/Li cell (0.01 V vs. Li/Li+). The metallic Mo nanoparticles are believed to be responsible for the enhanced cycling stability of the cell and act as the electronically conducting phase in the capacitive energy storage on the interfaces or grain boundaries of Mo/Li2Sx, nanocomposite. In addition, the Mo/Li2S nanocomposite can be used as a cathode material for lithium-sulfur batteries. (c) 2012 Elsevier Ltd. All rights reserved

Synthesis and electrochemical performance of graphene-like WS2

Graphene-like and platelike WS2 were obtained by solid-state reactions. High-resolution (HR) TEM, BET, and Raman scattering studies show that the graphene-like WS2 is a few-layer-structured material. It exhibits better electrochemical performances than the platelike WS2. Structural characterization indicates that metallic W and Li2S are the end products of discharge (0.01V versus Li+/Li), whereas metallic W and S are the recharge (3.00V) products. In addition, X-ray absorption near-edge structure (XANES) characterization shows that the d electrons of W deviate towards the Li (or S) atom during the discharge/charge process, thus forming a weak bond between W and Li2S (or S). Smashing the plate: Graphene-like WS2 exhibits better electrochemical performance than platelike WS2. XRD and X-ray absorption near-edge structure (XANES) analyses show that metallic W and Li2S are the products of discharge, whereas metallic W and S are the products of recharge (see figure). The d electrons of W deviate towards the Li (or S) atom during the discharge/charge process to form a weak bond between W and Li2S (or S). 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Electrode reactions of manganese oxides for secondary lithium batteries

Nanorods of MnO2, Mn3O4, Mn2O3 and MnO are synthesized by hydrothermal reactions and subsequent annealing. It is shown that though different oxides experience distinct phase transition processes in the initial discharge, metallic Mn and Li2O are the end products of discharge, while MnO is the end product of recharge for all these oxides between 0.0 and 3.0 V vs. Li+/Li. Of these 4 manganese oxides, MnO is believed the most promising anode material for lithium ion batteries while MnO2 is the most promising cathode material for secondary lithium batteries

Synthesis and Lithium Storage Mechanism of Ultrafine MoO₂ Nanorods

Ultrafine MoO₂ nanorods with a diameter of ∼5 nm were successfully synthesized by a nanocasting method using mesoporous silica SBA-15 as hard template. This material demonstrates high reversible capacity, excellent cycling performance, and good rate capacity as an anode electrode material for Li ion batteries. The significant enhancement in the electrochemical Li storage performance in ultrafine MoO₂ nanorods is attributed to the nanorod structure with small diameter and efficient one-dimensional electron transport pathways. Moreover, density functional theory calculations were performed to elucidate the Li uptake/removal mechanism in the MoO₂ electrodes, which can help us understand the unique cycling behavior of MoO₂ material

NMN reduced the level of ROS in aged porcine oocytes.

Images (A) and ROS level (B) at 0 h, AGED-24 h, AGED+NMN-24 h, AGED-48 h and AGED+NMN-48 h oocytes. Scale bars represented 100 μm. The expression of anti‐oxidative stress genes SOD1 (C) and Cat (D) in fresh and aged oocytes. *p < 0.05, **p < 0.01 indicated significant differences.</p