Genome-inspired search for new antibiotics. Isolation and structure determination of new 28-membered polyketide macrolactones, halstoctacosanolides A and B, from Streptomyces halstedii HC34

During the search for polyketide synthase (PKS) in the genome of Streptomyces halstedii HC34, we found clustered new genes which appeared to encode typical Type 1 PKSs beyond the cluster harboring the genes for the biosynthesis of antitumor antibiotic vicenistatin. The deduced domain configuration of these putative PKS genes allowed to predict a corresponding partial structure of polyketide, which was in turn materialized by isolation of new polyketide macrolactone halstoctacosanolides A and B from the fermentation broth of S. halstedii HC34. The structures of these metabolites were determined by spectroscopic means to have a novel 28-membered macrolactone structure. The partial structure deduced from the genetic data was completely compatible to the structures of halstoctacosanolides A and B. This success clearly demonstrates the present new approach of genome-inspired search for new antibiotics promising. Halstoctacosanolides A and B showed moderate antimicrobial activity against several microorganisms.     

Membrane Disruption and Enhanced Inhibition of Cell‐Wall Biosynthesis: A Synergistic Approach to Tackle Vancomycin‐Resistant Bacteria

Resistance to glycopeptide antibiotics, the drugs of choice for life‐threatening bacterial infections, is on the rise. In order to counter the threat of glycopeptide‐resistant bacteria, we report development of a new class of semi‐synthetic glycopeptide antibiotics, which not only target the bacterial membrane but also display enhanced inhibition of cell‐wall biosynthesis through increased binding affinity to their target peptides. The combined effect of these two mechanisms resulted in improved in vitro activity of two to three orders of magnitude over vancomycin and no propensity to trigger drug resistance in bacteria. In murine model of kidney infection, the optimized compound was able to bring bacterial burden down by about 6 logs at 12 mg kg^?1 with no observed toxicity. The results furnished in this report emphasize the potential of this class of compounds as future antibiotics for drug‐resistant Gram‐positive infections.     

Bionomic exploitation of a ratio-dependent predator–prey system

The present article deals with the problem of combined harvesting of a Michaelis–Menten-type ratio-dependent predator–prey system. The problem of determining the optimal harvest policy is solved by invoking Pontryagin's Maximum Principle. Dynamic optimization of the harvest policy is studied by taking the combined harvest effort as a dynamic variable. Computer simulations are carried out to illustrate our analytical findings. Biological and bioeconomical interpretations of the results are explained critically.     

Cellular NADH and NADPH Conformation as a Real-Time Fluorescence-Based Metabolic Indicator under Pressurized Conditions

Cellular conformation of reduced pyridine nucleotides NADH and NADPH sensed using autofluorescence spectroscopy is presented as a real-time metabolic indicator under pressurized conditions. The approach provides information on the role of pressure in energy metabolism and antioxidant defense with applications in agriculture and food technologies. Here, we use spectral phasor analysis on UV-excited autofluorescence from Saccharomyces cerevisiae (baker’s yeast) to assess the involvement of one or multiple NADH- or NADPH-linked pathways based on the presence of two-component spectral behavior during a metabolic response. To demonstrate metabolic monitoring under pressure, we first present the autofluorescence response to cyanide (a respiratory inhibitor) at 32 MPa. Although ambient and high-pressure responses remain similar, pressure itself also induces a response that is consistent with a change in cellular redox state and ROS production. Next, as an example of an autofluorescence response altered by pressurization, we investigate the response to ethanol at ambient, 12 MPa, and 30 MPa pressure. Ethanol (another respiratory inhibitor) and cyanide induce similar responses at ambient pressure. The onset of non-two-component spectral behavior upon pressurization suggests a change in the mechanism of ethanol action. Overall, results point to new avenues of investigation in piezophysiology by providing a way of visualizing metabolism and mitochondrial function under pressurized conditions.     

Gomisin M2 Ameliorates Atopic Dermatitis-like Skin Lesions via Inhibition of STAT1 and NF-κB Activation in 2,4-Dinitrochlorobenzene/Dermatophagoides farinae Extract-Induced BALB/c Mice

The extracts of Schisandra chinensis (Turcz.) Baill. (Schisandraceae) have various therapeutic effects, including inflammation and allergy. In this study, gomisin M2 (GM2) was isolated from S. chinensis and its beneficial effects were assessed against atopic dermatitis (AD). We evaluated the therapeutic effects of GM2 on 2,4-dinitrochlorobenzene (DNCB) and Dermatophagoides farinae extract (DFE)-induced AD-like skin lesions with BALB/c mice ears and within the tumor necrosis factor (TNF)-α and interferon (IFN)-γ-stimulated keratinocytes. The oral administration of GM2 resulted in reduced epidermal and dermal thickness, infiltration of tissue eosinophils, mast cells, and helper T cells in AD-like lesions. GM2 suppressed the expression of IL-1β, IL-4, IL-5, IL-6, IL-12a, and TSLP in ear tissue and the expression of IFN-γ, IL-4, and IL-17A in auricular lymph nodes. GM2 also inhibited STAT1 and NF-κB phosphorylation in DNCB/DFE-induced AD-like lesions. The oral administration of GM2 reduced levels of IgE (DFE-specific and total) and IgG2a in the mice sera, as well as protein levels of IL-4, IL-6, and TSLP in ear tissues. In TNF-α/IFN-γ-stimulated keratinocytes, GM2 significantly inhibited IL-1β, IL-6, CXCL8, and CCL22 through the suppression of STAT1 phosphorylation and the nuclear translocation of NF-κB. Taken together, these results indicate that GM2 is a biologically active compound that exhibits inhibitory effects on skin inflammation and suggests that GM2 might serve as a remedy in inflammatory skin diseases, specifically on AD.     

Fabrication and Mechanical Performance of Non-Crimp Unidirectional Jute-Yarn Preform-Based Composites

This work developed novel jute-yarn, non-crimp, unidirectional (UD) preforms and their composites, with three different types of warp jute yarns of varying linear densities and twists in the dry UD preforms, in order to present a possible solution to the detrimental effects of higher yarn twists and crimp at the warp–weft yarn interlacements of traditional, woven, preform-based composites on their mechanical properties. In the developed UD preforms, warp jute yarns were placed in parallel by using a wooden picture-frame pin board, with the minimal number of glass weft yarns to avoid crimp at the warp–weft yarns interlacements, which can significantly enhance the load-bearing ability of UD composites compared to traditional, woven, preform composites. It was found that an optimal combination of jute warp yarn linear densities and twists in the UD preforms is important to achieve the best possible mechanical properties of newly developed UD composites, because it encourages a proper polymer-matrix impregnation on jute fibres, leading to excellent fibre–matrix interface bonding. Composites made from the 25 lb/spindle jute warp yarn linear density (UD25) exhibited higher tensile and flexural properties than other UD composites (UD20, UD30). All the UD composites showed a much better performance compared to the traditional woven preform composites (W20), which were obviously related to the higher crimp and yarn interlacements, less load-carrying capacity, and poor fiber–matrix interfaces of W20 composites. UD25 composites exhibited a significant enhancement in tensile modulus by ~232% and strength by ~146%; flexural modulus by 138.5% and strength by 145% compared to W20 composites. This reveals that newly developed, non-crimp, UD preform composites can effectively replace the traditional woven composites in lightweight, load-bearing, complex-shaped composite applications, and hence, this warrants further investigations of the developed composites, especially on long-term and dynamic-loading mechanical characterizations.     

Transients and Evolution in NiTi

Many of the applications that seek to utilize shape memory alloys for their unique set of properties inevitably must deal, on some level, with the dimensional instability that is inherent to these materials under cyclic thermomechanical loading conditions. As a result, a better understanding of the transient and evolutionary behavior of a shape memory alloy is critical to both the successful design of useful actuation systems and development of accurate material models that can adequately capture the types of dimensional instability that can arise during component design. To this end, a set of experiments were conducted wherein the temperature cycling excursion was held fixed while the applied stress was varied. The results indicated that the extent of strain evolution produced under the initially applied stress has a significant impact on both the amount of transient that is observed as well as the rate of evolution observed under subsequent stress levels. In particular, lowering the applied stress to 50 MPa after cycling under an initial stress of 75 MPa did not stabilize the strain. However, lowering the applied stress to 50 MPa after cycling under an initial stress of 150 MPa produced a nearly saturated strain/temperature response. The thermomechanical observations are discussed in terms of the nature of strain evolution and its connection to the concept of a local/global minimization of the energy of the system, however, the exact mechanisms associated with these strain evolutions were not determined.     

Origin of the anomalous low temperature upturn in the resistivity of the electron-doped cuprate superconductors

The temperature, doping, and field dependences of the magnetoresistance (MR) in Pr2-xCexCuO4-delta films are reported. We distinguish between orbital MR, found when the magnetic field is applied perpendicular to the ab planes, and the nearly isotropic spin MR. The latter, the major MR effect in the superconducting samples, appears in the region of the doping-temperature phase diagram where drho/dT<0, or an upturn in the resistivity appears. We conclude that the upturn originates from spin scattering processes.     

Ballistic Impact Behaviour of Glass/Epoxy Composite Laminates Embedded with Shape Memory Alloy (SMA) Wires

This paper aims to estimate the enhancement in the energy absorption characteristics of the glass fiber reinforced composites (GFRP) by embedding prestrained pseudo-elastic shape memory alloy (SMA) that was used as a secondary reinforcement. The pseudo-elastic SMA (PE-SMA) embedded were in the form of wires and have an equiatomic composition (i.e., 50%–50%) of nickel (Ni) and titanium (Ti). These specimens are fabricated using a vacuum-assisted resin infusion process. The estimation is done for the GFRP and SMA/GFRP specimens at four different impact velocities (65, 75, 85, and 103 m/s) using a gas-gun impact set-up. At all different impact velocities, the failure modes change as we switch from GFRP to SMA/GFRP specimen. In the SMA/GFRP specimen, the failure mode changed from delamination in the primary region to SMA-pull out and SMA deformation. This leads to an increase in the ballistic limit. It is observed that energy absorbed by SMA/GFRP specimens is higher than the GFRP specimens subjected to the same levels of impact energy. To understand the damping capabilities of SMA embedment, vibration signals are captured, and the damping ratio is calculated. SMA dampens the vibrations imparted by the projectile to the specimen. The damping ratio of the SMA/GFRP specimens is higher than the GFRP specimens. The damping effect is more prominent below the ballistic limit when the projectile got rebounded (65 m/s).