Two‐dimensional polynomial type canonical relaxation oscillator model for p53 dynamics

p53 network, which is responsible for DNA damage response of cells, exhibits three distinct qualitative behaviours; low state, oscillation and high state, which are associated with normal cell cycle progression, cell cycle arrest and apoptosis, respectively. The experimental studies demonstrate that these dynamics of p53 are due to the ATM and Wip1 interaction. This paper proposes a simple two‐dimensional canonical relaxation oscillator model based on the identified topological structure of ATM and Wip1 interaction underlying these qualitative behaviours of p53 network. The model includes only polynomial terms that have the interpretability of known ATM and Wip1 interaction. The introduced model is useful for understanding relaxation oscillations in gene regulatory networks. Through mathematical analysis, we investigate the roles of ATM and Wip1 in forming of these three essential behaviours, and show that ATM and Wip1 constitute the core mechanism of p53 dynamics. In agreement with biological findings, we show that Wip1 degradation term is a highly sensitive parameter, possibly related to mutations. By perturbing the corresponding parameters, our model characterizes some mutations such as ATM deficiency and Wip1 overexpression. Finally, we provide intervention strategies considering our observation that Wip1 seems to be an important target to conduct therapies for these mutations.Inspec keywords: enzymes, molecular biophysics, molecular configurations, genetics, cellular biophysicsOther keywords: two‐dimensional polynomial type canonical relaxation oscillator model, p53 dynamics, p53 network, gene regulatory network, DNA damage response, normal cell cycle progression, cell cycle arrest, cell apoptosis, ATM interaction, Wip1 interaction, ataxia‐telangiectasia mutated interaction, wild‐type p53‐induced phosphatase 1 interaction, topological structure, mathematical analysis     

Non‐linear feedback control of the p 53 protein–mdm 2 inhibitor system using the derivative‐free non‐linear Kalman filter

It is proven that the model of the p 53–mdm 2 protein synthesis loop is a differentially flat one and using a diffeomorphism (change of state variables) that is proposed by differential flatness theory it is shown that the protein synthesis model can be transformed into the canonical (Brunovsky) form. This enables the design of a feedback control law that maintains the concentration of the p 53 protein at the desirable levels. To estimate the non‐measurable elements of the state vector describing the p 53–mdm 2 system dynamics, the derivative‐free non‐linear Kalman filter is used. Moreover, to compensate for modelling uncertainties and external disturbances that affect the p 53–mdm 2 system, the derivative‐free non‐linear Kalman filter is re‐designed as a disturbance observer. The derivative‐free non‐linear Kalman filter consists of the Kalman filter recursion applied on the linearised equivalent of the protein synthesis model together with an inverse transformation based on differential flatness theory that enables to retrieve estimates for the state variables of the initial non‐linear model. The proposed non‐linear feedback control and perturbations compensation method for the p 53–mdm 2 system can result in more efficient chemotherapy schemes where the infusion of medication will be better administered.Inspec keywords: proteins, molecular biophysics, biochemistry, Kalman filters, inverse problems, perturbation theoryOther keywords: nonlinear feedback control, p53 protein‐mdm2 inhibitor system, derivative‐free nonlinear Kalman filter, differential flatness theory, protein synthesis loop, diffeomorphism, protein synthesis model, feedback control law, nonmeasurable elements, modelling uncertainties, inverse transformation, nonlinear model, perturbation compensation method, chemotherapy schemes, medication infusion     

Synthesis of silver nanoparticles by Bacillus subtilis T‐1 growing on agro‐industrial wastes and producing biosurfactant

In this study, culture supernatnats of Bacillus subtilis T‐1 growing on brewery effluents and molasses was used for silver nanoparticles (Ag‐NPs) synthesis. The biosurfactant production of B. subtilis T‐1 was confirmed by the detection of genes in the genome and by the identification of the product in the supernatants. The genes for synthesis of surfactin (sfp, srfAA) and iturin (ituC) were noted by PCR reactions. Also, in examined culture supernatants the presence of C₁₃, C₁₄ and C₁₅ surfactin homologues with the sodiated molecules [M + Na]⁺ at m /z 1030, 1044 and 1058 was confirmed using LC/MS/MS analysis. The formation of NPs in the culture supernatants was confirmed by UV–vis spectroscopy. The dynamic light scattering measurements and transmission electron microscopy images showed the nanometric sizes of the biosynthesised Ag‐NPs which ranged from several nm to several tens of nm depending on the used culture supernatant. Biological properties of Ag‐NPs were evaluated by binding of Ag‐NPs with DNA isolated from the Escherichia coli ATCC 25922 and B. subtilis ATCC 6633. Biogenic Ag‐NPs were actively bound to DNA in increased concentration which could be the one important mode of antibacterial action of the Ag‐NPs.Inspec keywords: silver, nanoparticles, nanofabrication, materials preparation, microorganisms, antibacterial activity, industrial waste, agrochemicals, surfactants, breweries, genomics, genetics, chromatography, mass spectroscopic chemical analysis, ultraviolet spectroscopy, visible spectroscopy, spectrochemical analysis, light scattering, transmission electron microscopy, DNA, bonds (chemical), biochemistry, molecular biophysics, nanobiotechnology, biological techniques, particle size, enzymesOther keywords: silver nanoparticle synthesis, Bacillus subtilis T‐1 growth, agro‐industrial waste, biosurfactant production, brewery effluent, molasses, Ag‐NP synthesis, B. subtilis T‐1, gene detection, genome, supernatant product identification, surfactin synthesis, sfp, srfAA, iturin synthesis, ituC, PCR reaction, C₁₃ surfactin homologue, C₁₄ surfactin homologue, C₁₅ surfactin homologue, sodiated molecules, LC‐MS‐MS analysis, UV‐vis spectroscopy, dynamic light scattering measurement, transmission electron microscopy image, Ag‐NP nanometric size range, Ag‐NP biosynthesis, used culture supernatant dependence, biological properties, DNA isolation, Escherichia coli ATCC 25922, B. subtilis ATCC 6633, biogenic Ag‐NP‐DNA binding, Ag‐NP antibacterial action, Ag     

Pathway‐based protein–protein association network to explore mechanism of α‐glucosidase inhibitors from Scutellaria baicalensis Georgi against type 2 diabetes

Natural products have been widely used in the treatment of type 2 diabetes (T2D). However, their mechanisms are often obscured due to multi‐components and multi‐targets. The authors constructed a pathway‐based protein–protein association (PPA) network for target proteins of 13 α‐glucosidase inhibitors (AGIs) identified from Scutellaria baicalensis Georgi (SBG), designed to explore the underlying mechanisms. This network contained 118 nodes and 1167 connections. An uneven degree distribution and small‐world property were observed, characterised by high clustering coefficient and short average path length. The PPA network had an inherent hierarchy as C(k)∼k ^−0.71. It also exhibited potential weak disassortative mixing pattern, coupled with a decreased function Knn (k) and negative value of assortativity coefficient. These properties indicated that a few nodes were crucial to the network. PGH2, GNAS, MAPK1, MAPK3, PRKCA, and MAOA were then identified as key targets with the highest degree values and centrality indices. Additionally, a core subnetwork showed that chrysin, 5,8,2′‐trihydroxy‐7‐methoxyflavone, and wogonin were the main active constituents of these AGIs, and that the serotonergic synapse pathway was the critical pathway for SBG against T2D. The application of a pathway‐based protein–protein association network provides a novel strategy to explore the mechanisms of natural products on complex diseases.     

Postprandial anti‐hyperglycemic activity of marine Streptomyces coelicoflavus SRBVIT13 mediated gold nanoparticles in streptozotocin induced diabetic male albino Wister rats

The present study focuses on the biosynthesis of gold nanoparticles (AuNPs) using Streptomyces coelicoflavus (S. coelicoflavus) SRBVIT13 isolated from marine salt pan soils collected from Ongole, Andhra Pradesh, India. The biosynthesised AuNPs are characterised by UV–visible spectroscopy, X‐ray diffraction, Fourier transform infrared spectroscopy, high‐resolution transmission electron microscopy and energy‐dispersive X‐ray analysis. Transmission electron microscopy study suggests that the biosynthesised AuNPs are spherical in shape within a size range of 12–20 nm (mean diameter as 14 nm). The anti‐type II diabetes activity of AuNPs is carried out by testing it in vitro α ‐glucosidase and α ‐amylase enzyme inhibition activity and in vivo postprandial anti‐hyperglycemic activity in sucrose and glucose‐loaded streptozotocin induced diabetic albino Wister rats. AuNPs has shown a significant inhibitory activity of 84.70 and 87.82% with IC₅₀ values of 67.65 and 65.59 μg/mL to α ‐glucosidase and α ‐amylase enzymes, while the diabetic rats have shown significant reduction in the post postprandial blood glucose level by 57.80 and 88.09%, respectively compared with control group after AuNPs treatment at the concentration of 300 and 600 mg/kg body weight. Hence, this biosynthesised AuNPs might be useful in combating type II diabetes mellitus for the betterment of human life.Inspec keywords: gold, nanoparticles, ultraviolet spectra, visible spectra, X‐ray diffraction, Fourier transform infrared spectra, transmission electron microscopy, X‐ray chemical analysis, diseases, enzymes, nanomedicine, biochemistry, spectrochemical analysisOther keywords: gold nanoparticles, Streptomyces coelicoflavus SRBVIT13, biosynthesis, UV–visible spectroscopy, X‐ray diffraction, Fourier transform infrared spectroscopy, high‐resolution transmission electron microscopy, energy‐dispersive X‐ray analysis, antitype II diabetes activity, in vitro enzyme inhibition activity, in vivo postprandial antihyperglycemic activity, streptozotocin induced diabetic albino Wister rats, type II diabetes mellitus, Au     

Characterisation of sol–gel method synthesised MgZnFe2 O4 nanoparticles and its cytotoxic effects on breast cancer cell line,MDA MB‐231 in vitro

In this study, nanocrystalline magnesium zinc ferrite nanoparticles were successfully prepared by a simple sol–gel method using copper nitrate and ferric nitrate as raw materials. The calcined samples were characterised by differential thermal analysis/thermogravimetric analysis, Fourier transform infrared spectroscopy and X‐ray diffraction. Transmission electron microscopy revealed that the average particle size of the calcined sample was in a range of 17–41 nm with an average of 29 nm and has spherical size. A cytotoxicity test was performed on human breast cancer cells (MDA MB‐231) and (MCF‐7) at various concentrations starting from (0 µg/ml) to (800 µg/ml). The sample possessed a mild toxic effect toward MDA MB‐231 and MCF‐7 after being examined with MTT (3‐[4, 5‐dimethylthiazol‐2‐yl]‐2, 5 diphenyltetrazolium bromide) assay for up to 72 h of incubation. Higher reduction of cells viability was observed as the concentration of sample was increased in MDA MB‐231 cell line than in MCF‐7. Therefore, further cytotoxicity tests were performed on MDA MB‐231 cell line.Inspec keywords: sol‐gel processing, nanoparticles, nanofabrication, magnesium compounds, zinc compounds, toxicology, biological organs, cancer, cellular biophysics, nanomedicine, calcination, differential thermal analysis, Fourier transform infrared spectra, X‐ray diffraction, transmission electron microscopy, particle size, organic compoundsOther keywords: sol‐gel method, cytotoxic effects, breast cancer cell line, MDA MB‐231 in vitro, nanocrystalline magnesium zinc ferrite nanoparticles, copper nitrate, ferric nitrate, raw materials, calcined samples, differential thermal analysis, thermogravimetric analysis, Fourier transform infrared spectroscopy, X‐ray diffraction, transmission electron microscopy, average particle size, cytotoxicity testing, human breast cancer cells, mild toxic effect, 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyltetrazolium bromide) assay, cell viability, MCF‐7, MDA MB‐231 cell line, size 17 nm to 41 nm     

Design and development of a portable resistive sensor based on α‐MnO2/GQD nanocomposites for trace quantification of Pb(II) in water

The occurrence of heavy metal ions in food chain is appearing to be a major problem for mankind. The traces of heavy metals, especially Pb(II) ions present in water bodies remains undetected, untreated, and it remains in the food cycle causing serious health hazards for human and livestock. The consumption of Pb(II) ions may lead to serious medical complications including multiple organ failure which can be fatal. The conventional methods of heavy metal detection are costly, time‐consuming and require laboratory space. There is an immediate need to develop a cost‐effective and portable sensing system which can easily be used by the common man without any technical knowhow. A portable resistive device with miniaturized electronics is developed with microfluidic well and α‐MnO₂/GQD nanocomposites as a sensing material for the sensitive detection of Pb(II). α‐MnO₂/GQD nanocomposites which can be easily integrated with the miniaturized electronics for real‐time on‐field applications. The proposed sensor exhibited a tremendous potential to be integrated with conventional water purification appliances (household and commercial) to give an indication of safety index for the drinking water. The developed portable sensor required low sample volume (200 µL) and was assessed within the Pb(II) concentration range of 0.001 nM to 1 uM. The Limit of Detection (LoD) and sensitivity was calculated to be 0.81 nM and 1.05 kΩ/nM/mm², and was validated with the commercial impedance analyser. The shelf‐life of the portable sensor was found to be ∼45 days.