Metformin, phenformin, and galegine inhibit complex IV activity and reduce glycerol-derived gluconeogenesis.

SignificanceMetformin is the most commonly prescribed drug for the treatment of type 2 diabetes mellitus, yet the mechanism by which it lowers plasma glucose concentrations has remained elusive. Most studies to date have attributed metformin's glucose-lowering effects to inhibition of complex I activity. Contrary to this hypothesis, we show that inhibition of complex I activity in vitro and in vivo does not reduce plasma glucose concentrations or inhibit hepatic gluconeogenesis. We go on to show that metformin, and the related guanides/biguanides, phenformin and galegine, inhibit complex IV activity at clinically relevant concentrations, which, in turn, results in inhibition of glycerol-3-phosphate dehydrogenase activity, increased cytosolic redox, and selective inhibition of glycerol-derived hepatic gluconeogenesis both in vitro and in vivo.

Genome-Wide Characterization of Somatic Mutation Patterns in Cloned Dogs Reveals Implications for Neuronal Function, Tumorigenesis, and Aging.

Studies on somatic mutations in cloned animals have revealed slight genetic variances between clones and their originals, but have yet to identify the precise effects of these differences within the organism. Somatic mutations contribute to aging and are implicated in tumor development and other age-related diseases. Thus, we compared whole genome sequencing data from an original dog with that of cloned dogs, identifying candidate somatic mutations that were disproportionately located within genes previously implicated in aging. The substitutional signature of cloning-specific somatic mutations mirrored the uniform distribution characteristic of the signature associated with human aging. Further analysis of genes revealed significant enrichment of traits associated with body size as well as the molecular mechanisms underlying neuronal function and tumorigenesis. Overall, the somatic mutations found in cloned dogs may indicate a conserved mechanism driving aging across species and a broad spectrum of pathway alterations.

Reduction of Structural Defects in the GaSb Buffer Layer on (001) GaP/Si for High Performance InGaSb/GaSb Quantum Well Light-Emitting Diodes.

Monolithic integration of GaSb-based optoelectronic devices on Si is a promising approach for achieving a low-cost, compact, and scalable infrared photonics platform. While tremendous efforts have been put into reducing dislocation densities by using various defect filter layers, exploring other types of extended crystal defects that can exist on GaSb/Si buffers has largely been neglected. Here, we show that GaSb growth on Si generates a high density of micro-twin (MT) defects as well as threading dislocations (TDs) to accommodate the extremely large misfit between GaSb and Si. We found that a 250 nm AlSb single insertion layer is more effective than AlSb/GaSb strained superlattices in reducing both types of defects, resulting in a 4× and 13× reduction in TD density and MT density, respectively, compared with a reference sample with no defect filter layer. InGaSb quantum well light-emitting diodes were grown on the GaSb/Si templates, and the effect of TD density and MT density on their performance was studied. This work shows the importance of using appropriate defect filter layers for high performance GaSb-based optoelectronic devices on standard on-axis (001) Si via direct epitaxial growth.

Enhanced Photoluminescence of 1.3 µm InAs Quantum Dots Grown on Ultrathin GaAs Buffer/Si Templates by Suppressing Interfacial Defect Emission.

We report on the photoluminescence enhancement of 1.3 µm InAs quantum dots (QDs) epitaxially grown on an ultrathin 250 nm GaAs buffer on a Si substrate. Decreasing the GaAs buffer thickness from 1000 to 250 nm was found to not only increase the coalesced QD density from 6.5 × 108 to 1.9 × 109 cm-2 but also decrease the QD photoluminescence emission intensity dramatically. Inserting an Al0.4Ga0.6As potential barrier layer maintained strong photoluminescence from the QDs by effectively suppressing carrier leakage to the GaAs/Si interfacial region even when the GaAs buffer was thinned to 250 nm. We then fabricated a light-emitting diode using the ultrathin 250 nm GaAs buffer on Si and confirmed strong electroluminescence peaking at 1.28 µm without interfacial defect emission at room temperature. We believe that this work is promising for monolithically integrated evanescent Si lasers using InAs/GaAs QDs.

High-Performance Flexible InAs Thin-Film Photodetector Arrays with Heteroepitaxial Growth Using an Abruptly Graded InxAl1-xAs Buffer.

Current infrared thermal image sensors are mainly based on planar firm substrates, but the rigid form factor appears to restrain the versatility of their applications. For wearable health monitoring and implanted biomedical sensing, transfer of active device layers onto a flexible substrate is required while controlling the high-quality crystalline interface. Here, we demonstrate high-detectivity flexible InAs thin-film mid-infrared photodetector arrays through high-yield wafer bonding and a heteroepitaxial lift-off process. An abruptly graded InxAl1-xAs (0.5 < x < 1) buffer was found to drastically improve the lift-off interface morphology and reduce the threading dislocation density twice, compared to the conventional linear grading method. Also, our flexible InAs photodetectors showed excellent optical performance with high mechanical robustness, a peak room-temperature specific detectivity of 1.21 × 109 cm-Hz1/2/W at 3.4 µm, and excellent device reliability. This flexible InAs photodetector enabled by the heteroepitaxial lift-off method shows promise for next-generation thermal image sensors.