Rational Biosynthetic Engineering for Optimization of Geldanamycin Analogues

Tailor made : We report the rational biosynthesis of C15 hydroxylated non‐quinone geldanamycin analogues by site‐directed mutagenesis of the geldanamycin polyketide synthase (PKS), together with a combination of post‐PKS tailoring genes. Rational biosynthetic engineering allowed the generation of geldanamycin derivatives, such as DHQ3 illustrated in the figure, which had superior pharmacological properties in comparison to the parent compound.

     

Extraction of interface states at emitter–base heterojunctions in AlGaAs/GaAs heterostructure bipolar transistors using sub-bandgap photonic excitation

Distribution of interface states at the emitter–base heterojunctions in heterostructure bipolar transistors (HBTs) is characterized by using current–voltage characteristics using sub-bandgap photonic excitation. Sub-bandgap photonic source with a photon energy E_ph which is less than the energy bandgap E_g (E_g,GaAs = 1.42, E_g,AlGaAs = 1.76 eV) of emitter, base, and collector of HBTs, is employed for exclusive excitation of carriers only from the interface states in the photo-responsive energy range at emitter–base heterointerface. The proposed method is applied to an Al_0.3Ga_0.7As/GaAs HBT (A_E = W_E × L_E = 250 × 100 μm²) with E_ph = 0.943 eV and P_opt = 3 mW. Extracted interface trap density D_it was observed to be D_it,max  4.2 × 10¹² eV⁻¹ cm⁻² at emitter–base heterointerface.     

Morphology and distribution of antennal sensilla in egg parasitoid,Ooencyrtus nezarae (Hymenoptera: Encyrtidae)

Morphology of antennal sensilla and their distribution were investigated in adults of Ooencyrtus nezarae, an egg parasitoid of Riptortus pedestris, using scanning electron microscopy. Male antennae was found to be significantly greater in overall length than female antennae. The antenna of O. nezarae was composed of the radicula, scape, pedicel, funicle and clava in both sexes, with seven types of sensilla identified: sensillum trichodea; s. finger‐like; s. placoidea; s. chaetica; s. basiconica; s. coeloconica, and s. campaniform. They occur in varying number and distribution along the antennae. Two sensillum types were further categorized into additional subtypes, with two subtypes in s. trichodea and three in s. chaetica. Among all characterized sensilla, s. trichodea subtype 1 and s. placoidea were multiporous, indicating that the primary function of these sensilla is olfactory. Sensillum trichodea was the most abundant sensillum type on the antennae of both sexes. Sexual dimorphism was only observed from the subtype 1 sensilla of s. trichodea in males and the subtype 3 sensilla of s. chaetica in females. The morphological information established in our study may provide useful information for further investigations in sensory physiological function of each morphological type of sensilla and their related behavior in this egg parasitoid.     

Development of microbial genome-probing microarrays using digital multiple displacement amplification of uncultivated microbial single cells

A crucial problem in the use of previously developed genome-probing microarrays (GPM) has been the inability to use uncultivated bacterial genomes to take advantage of the high sensitivity and specificity of GPM in microbial detection and monitoring. We show here a method, digital multiple displacement amplification (MDA), to amplify and analyze various genomes obtained from single uncultivated bacterial cells. We used 15 genomes from key microbes involved in dichloromethane (DCM)-dechlorinating enrichment as microarray probes to uncover the bacterial population dynamics of samples without PCR amplification. Genomic DNA amplified from single cells originating from uncultured bacteria with 80.3-99.4% similarity to 16S rRNA genes of cultivated bacteria. The digital MDA-GPM method successfully monitored the dynamics of DCM-dechlorinating communities from different phases of enrichment status. Without a priori knowledge of microbial diversity, the digital MDA-GPM method could be designed to monitor most microbial populations in a given environmental sample.     

Analysis of yeast and archaeal population dynamics in kimchi using denaturing gradient gel electrophoresis

Kimchi is a traditional Korean food that is fermented from vegetables such as Chinese cabbage and radish. Many bacteria are involved in kimchi fermentation and lactic acid bacteria are known to perform significant roles. Although kimchi fermentation presents a range of environmental conditions that could support many different archaea and yeasts, their molecular diversity within this process has not been studied. Here, we use PCR-denaturing gradient gel electrophoresis (DGGE) targeting the 16S and 26S rRNA genes, to characterize bacterial, archaeal and yeast dynamics during various types of kimchi fermentation. The DGGE analysis of archaea expressed a change of DGGE banding patterns during kimchi fermentation, however, no significant change was observed in the yeast DGGE banding patterns during kimchi fermentation. No significant difference was indicated in the archaeal DGGE profile among different types of kimchi. In the case of yeasts, the clusters linked to the manufacturing corporation. Haloarchaea such as Halococcus spp., Natronococcus spp., Natrialba spp. and Haloterrigena spp., were detected as the predominant archaea and Lodderomyces spp., Trichosporon spp., Candida spp., Saccharomyces spp., Pichia spp., Sporisorium spp. and Kluyveromyces spp. were the most common yeasts.     

Thermal Management Enables Bright and Stable Perovskite Light-Emitting Diodes

The performance of lead-halide perovskite light-emitting diodes (LEDs) has increased rapidly in recent years. However, most reports feature devices operated at relatively small current densities (<500 mA cm⁻²) with moderate radiance (<400 W sr⁻¹ m⁻²). Here, Joule heating and inefficient thermal dissipation are shown to be major obstacles toward high radiance and long lifetime. Several thermal management strategies are proposed in this work, such as doping charge-transport layers, optimizing device geometry, and attaching heat spreaders and sinks. Combining these strategies, high-performance perovskite LEDs are demonstrated with maximum radiance of 2555 W sr⁻¹ m⁻², peak external quantum efficiency (EQE) of 17%, considerably reduced EQE roll-off (EQE > 10% to current densities as high as 2000 mA cm⁻²), and tenfold increase in operational lifetime (when driven at 100 mA cm⁻²). Furthermore, with proper thermal management, a maximum current density of 2.5 kA cm⁻² and an EQE of ≈1% at 1 kA cm⁻² are shown using electrical pulses, which represents an important milestone toward electrically driven perovskite lasers.     

Tracking the Fate of Porous Silicon Nanoparticles Delivering a Peptide Payload by Intrinsic Photoluminescence Lifetime

A nanoparticle system for systemic delivery of therapeutics is described, which incorporates a means of tracking the fate of the nanocarrier and its residual drug payload in vivo by photoluminescence (PL). Porous silicon nanoparticles (PSiNPs) containing the proapoptotic antimicrobial peptide payload, _D[KLAKLAK]₂, are monitored by measurement of the intrinsic PL intensity and the PL lifetime of the nanoparticles. The PL lifetime of the PSiNPs is on the order of microseconds, substantially longer than the nanosecond lifetimes typically exhibited by conventional fluorescent tags or by autofluorescence from cells and tissues; thus, emission from the nanoparticles is readily discerned in the time‐resolved PL spectrum. It is found that the luminescence lifetime of the PSiNP host decreases as the nanoparticle dissolves in phosphate‐buffered saline solution (37 °C), and this correlates with the extent of release of the peptide payload. The time‐resolved PL measurement allows tracking of the in vivo fate of PSiNPs injected (via tail vein) into mice. Clearance of the nanoparticles through the liver, kidneys, and lungs of the animals is observed. The luminescence lifetime of the PSiNPs decreases with increasing residence time in the mice, providing a measure of half‐life for degradation of the drug nanocarriers.     

The use of acellular dermal matrix in immediate two-stage prosthetic breast reconstruction provides protection from postmastectomy radiation therapy: a clinicopathologic perspective

Although there is ample evidence showing that radiation therapy increases the risk of complications of breast reconstruction, the efficacy of human acellular dermal matrix (CGCryoDerm®) in immediate tissue expander breast reconstruction in the setting of postmastectomy radiation therapy has not been fully elucidated. In this study, we report our institutional experience with pertinent refined surgical technique, and determine whether acellular dermal matrices have a protective effect in this increasingly prevalent clinical setting. Twenty-six patients who underwent immediate two-stage breast reconstruction in the setting of postmastectomy radiation therapy with at least 2 years of follow-up were retrieved. Fifteen patents were reconstructed with ADM, whereas 11 patients were reconstructed without ADM. The occurrence of complications was assessed according to the reconstruction type (with ADM vs without ADM). Furthermore, in patients reconstructed with ADM (n?=?15), immunohistochemistry was performed to analyze the breast capsule with ADM compared with that without ADM in the same patient, according to the expression of alpha-smooth muscle actin (α-SMA). The occurrence of complications was significantly associated with the reconstruction type (with ADM vs. without ADM, p = 0.015). On the basis of the results of α-SMA staining, α-SMA+ myofibroblasts were relatively highly expressed throughout the breast capsule without ADM. On the contrary, α-SMA+ myofibroblasts present at the breast capsule adjacent to the ADM were scarce and irregularly scattered. Use of an acellular dermal matrix may be recommended to patients who are concerned about complications after immediate two-stage breast reconstruction in the setting of postmastectomy radiation therapy.