We have compared the shot-noise properties at T = 4.2 K of a double-barrier resonant-tunneling diode and a superlattice tunnel diode, both of which exhibit negative differential-conductance (NDC) in their current-voltage characteristics. While the noise spectral density of the former device was greatly enhanced over the Poissonian value of 2eI in the NDC region, that of the latter device remained 2eI. This result implies that charge accumulation, not system instability, is responsible for shot-noise enhancement in NDC devices.

Core/shell heterostructure nanowires are one of the most interesting mesoscopic systems potentially suitable for the study of quantum interference phenomena. Here, we report on experimental observations of both the Aharonov-Bohm (h/e) and the Altshuler-Aronov-Spivak (h/2e) oscillations in radial core/shell (In2O3/InOx) heterostructure nanowires. For a long channel device with a length-to-width ratio of about 33, the magnetoresistance curves at low temperatures exhibited a crossover from low-field h/2e oscillation to high-field h/ e oscillation. The relationship between the oscillation period and the core width was investigated for freestanding or substrate-supported devices and indicated that the current flows dominantly through the core/shell interface.

We report on the fabrication and measurements of a superconducting junction of a single-crystalline Au nanowire, connected to Al electrodes. The current-voltage characteristic curve shows a clear supercurrent branch below the superconducting transition temperature of Al and quantized voltage plateaus on application of microwave radiation, as expected from Josephson relations. Highly transparent (0.95) contacts very close to an ideal limit of 1 are formed at the interface between the normal metal (Au) and the superconductor (Al). The very high transparency is ascribed to the single crystallinity of a Au nanowire and the formation of an oxide-free contact between Au and Al. The subgap structures of the differential conductance are well explained by coherent multiple Andreev reflections (MAR), the hallmark of mesoscopic Josephson junctions. These observations demonstrate that single crystalline Au nanowires can be employed to develop novel quantum devices utilizing coherent electrical transport.

Acinetobactin is a major siderophore utilized by the human pathogen Acinetobacter baumannii. The rapid acquisition of drug resistance by A. baumannii has garnered concern globally. Herein, acinetobactin and systematically generated analogues were prepared and characterized; the binding and cellular delivery of Fe(III) by the analogues were evaluated. This investigation not only led to the clarification of the physiologically relevant acinetobactin structure but also revealed several key structural elements for its functionality as a siderophore.

This Highlight covers recently unveiled biochemical aspects the acinetobactin metabolism, a central iron acquisition mechanism of Acinetobacter baumannii, in addition to various efforts for therapeutic application of these findings.

The stereoselective synthesis of fimsbactin A, a siderophore of the human pathogen Acinetobacter baumannii, was established. Based on this synthetic route, various fimsbactin stereoisomeric analogues were generated and tested for their iron delivery activity for A. baumannii. This investigation revealed that the fimsbactin uptake machinery in this bacterium was indeed highly stereoselective in substrate recognition.

Total synthesis of anguibactin was accomplished for the first time, and the following biochemical characterizations allowed for the determination of its Fe­(III) binding mode as well as the demonstration of its iron delivery capability for Acinetobacter baumannii. These properties, in addition to the thermal stability over acinetobactin, render anguibactin as a competent surrogate siderophore that can be useful for the future development of a siderophore-based antibiotic delivery system against A. baumannii.

Edited by Jeffrey PessinMitsugumin 53 (MG53) is an E3 ligase that interacts with and ubiquitinates insulin receptor substrate-1 (IRS-1) in skeletal muscle; thus, an MG53-IRS-1 interaction disruptor (MID), which potentially sensitizes insulin signaling with an elevated level of IRS-1 in skeletal muscle, is an excellent candidate for treating insulin resistance. To screen for an MID, we developed a bimolecular luminescence complementation system using an N-terminal luciferase fragment fused with IRS-1 and a C-terminal luciferase fragment fused with an MG53 C14A mutant that binds to IRS-1 but does not have E3 ligase activity. An MID, which was discovered using the bimolecular luminescence complementation system, disrupted the molecular association of MG53 with IRS-1, thus abolishing MG53-mediated IRS-1 ubiquitination and degradation. Thus, the MID sensitized insulin signaling and increased insulin-elicited glucose uptake with an elevated level of IRS-1 in C2C12 myotubes. These data indicate that this MID holds promise as a drug candidate for treating insulin resistance.Noninsulin-dependent diabetes mellitus (type 2 diabetes) has become a worldwide epidemic disease due to the increased incidence of obesity. Insulin receptor (IR) and insulin receptor substrate (IRS) 4 are inactivated by elevated serum levels of free fatty acids, leading to insulin resistance and noninsulin-dependent diabetes mellitus (1-3). Because skeletal muscle is the largest organ participating in glucose uptake, exercise-induced skeletal muscle development is an excellent treatment for insulin resistance. However, no current candidates target skeletal muscle to treat insulin resistance.Mitsugumin 53 (MG53), which is also called tripartite motifcontaining protein 72 (TRIM72) and which is largely expressed in skeletal muscle, was independently identified by proteomic analysis of lipid rafts and triad-rich membranes (4). MG53 contains a tripartite domain (an E3 ligase RING domain, a B-box, and two coiled-coil domains) and a SPRY domain. Insulin-like growth factor-1 (IGF-1) initiates MyoD activation via an IGF-1 receptor-PI3K-Akt pathway during skeletal myogenesis (5, 6). MyoD and myocyte enhancer factor 2 (MEF2) binds to two proximal E-boxes and an MEF2 site in MG53 promoter, activating MG53 gene transcription (7). The MG53 protein interacts with IRS-1 and focal adhesion kinase (FAK), inducing IRS-1 and FAK ubiquitination and degradation in skeletal muscle with the help of E2 ligase UBE2H (8 -10). Moreover, RING domain-disrupted MG53 mutants (⌬R and C14A) abolish IRS-1 and FAK ubiquitination and degradation in skeletal muscle, indicating that MG53 is an E3 ligase that targets IRS-1 and FAK.Systemic MG53 ablation abrogates IRS-1 ubiquitination and degradation in skeletal and cardiac muscle, leading to elevated IRS-1 expression level and increased insulin signaling (8, 9). Thus, MG53 knock-out mice do not develop diet-induced insulin resistance. In contrast, skeletal muscle-specific MG53 transgenic mice exhibit metabolic disorders such as obesity, ...