The WWOX/HIF1A Axis Downregulation Alters Glucose Metabolism and Predispose to Metabolic Disorders

Recent reports indicate that the hypoxia-induced factor (HIF1α) and the Warburg effect play an initiating role in glucotoxicity, which underlies disorders in metabolic diseases. WWOX has been identified as a HIF1α regulator. WWOX downregulation leads to an increased expression of HIF1α target genes encoding glucose transporters and glycolysis’ enzymes. It has been proven in the normoglycemic mice cells and in gestational diabetes patients. The aim of the study was to determine WWOX’s role in glucose metabolism regulation in hyperglycemia and hypoxia to confirm its importance in the development of metabolic disorders. For this purpose, the WWOX gene was silenced in human normal fibroblasts, and then cells were cultured under different sugar and oxygen levels. Thereafter, it was investigated how WWOX silencing alters the genes and proteins expression profile of glucose transporters and glycolysis pathway enzymes, and their activity. In normoxia normoglycemia, higher glycolysis genes expression, their activity, and the lactate concentration were observed in WWOX KO fibroblasts in comparison to control cells. In normoxia hyperglycemia, it was observed a decrease of insulin-dependent glucose uptake and a further increase of lactate. It likely intensifies hyperglycemia condition, which deepen the glucose toxic effect. Then, in hypoxia hyperglycemia, WWOX KO caused weaker glucose uptake and elevated lactate production. In conclusion, the WWOX/HIF1A axis downregulation alters glucose metabolism and probably predispose to metabolic disorders.     

Symbolic analysis approach to settling time minimization in sc networks

The paper presents a method of settling time minimization in switched capacitor (SC) circuits. This problem has been discussed in recent papers because of high-frequency applications of SC networks. In comparison with the methods elaborated up to now and limited to biquads, the method presented in this paper can be used for an SC circuit containing an arbitrary number of operational amplifiers coupled together in each switching state and modelled as ideal transconductances. the fifth-order ladder bilinear SC filter is considered for illustration of the method and SPICE simulations.     

Modelling of the Corynebacterium glutamicum biosynthesis under aerobic fermentation conditions

This work concerns the modelling of the Corynebacterium glutamicum biosynthesis. At the beginning, the impulsive growth model of C. glutamicum under glutamate inhibition is established. According to this model, the analysis of the bioprocess stability is presented. Then, new objective functions are proposed and optimisation of C. glutamicum growth is presented. The results of the optimisation indicate that, although the growth of C. glutamicum is an aerobic process, the maximum of biomass productivity occurs under controlled penetration into the area of aerobic fermentation. Analytical results presented in this work are validated by numerical simulations.     

Impedance study of the ion-to-electron transduction process for carbon cloth as solid-contact material in potentiometric ion sensors

Carbon cloth was studied as solid-contact material in potentiometric ion sensors by using electrochemical impedance spectroscopy and potentiometry. The ion-to-electron transduction process was studied by electrochemical impedance spectroscopy by using a two-electrode symmetrical cell where a liquid electrolyte was sandwiched between two solid electrodes, including bare glassy carbon (GC), GC/carbon cloth and GC/poly(3,4-ethylenedioxythiophene). Impedance data for different electrode/electrolyte combinations were evaluated and compared. Solid-contact K⁺-selective electrodes were fabricated by coating the carbon cloth with a conventional plasticized PVC-based K⁺-selective membrane via drop casting. These K⁺-sensors showed proper analytical performance and acceptable long-term potential stability (potential drift ≈ 1 mV/day). Solid contact reference electrodes were fabricated in an analogous manner by coating the carbon cloth with a plasticized PVC membrane containing a moderately lipophilic salt. The results indicate that carbon cloth can be used as a solid-contact material in potentiometric ion sensors and pseudo-reference electrodes.     

Formation of mesoglobules in aqueous media from thermo-sensitive poly(ethoxytriethyleneglycol acrylate)

A series of six poly(ethoxytriethyleneglycol acrylate) (PETEGA) homopolymers were synthesized by atom transfer radical polymerization, reversible addition-fragmentation transfer polymerization, and anionic polymerization in order to cover a molecular weight range from 7,000 to 40,000 Da. The polymers exhibited a lower critical solution temperature (LCST) behavior in water, which was observed by the occurrence of a cloud point (CP) at around 35 °C. The transmittance of visible light versus temperature dependence overlapped during the cooling and the heating cycles, showing almost a complete lack of hysteresis. Moreover, instead of the occurrence of an uncontrolled macroscopic phase separation, stable colloidal aggregates (mesoglobules) of narrow distribution in particle size were formed in water at temperatures above the LCST of PETEGA at 1 g L⁻¹ solutions. The dimensions of the mesoglobules ranged from 91 to 235 nm, and particle size was not influenced by the molecular weight of PETEGA. Temperature changes caused considerable variations of the mesoglobules dimensions, which were smaller at higher temperatures. The addition of an anionic surfactant simultaneously increased the CP values by 4–6 °C and lowered the dimensions of the mesoglobules.     

Druckstandfestigkeit und Betriebseigenschaften von Doppelwellendichtungen

The strength and operating properties of wave‐ring gaskets are analyzed. A cylindrical shell of constant mean thickness is introduced to simulate the gasket. It is assumed that the shell is simply supported at the inner surface of the seat. The influence of certain geometric, material and assembly parameters on the strength and leak‐tightness of the closure is investigated. The results are illustrated by a numerical example. For the assumed material of the gasket and several fixed data the other parameters of the closure are examined. The region of admissible solutions for the gasket parameters such as dimensions, applied assembly clearance and pressure is determined.     

Molecular orientation and stress in biaxially deformed polymers. II. Steady potential flow

The development of biaxial segmental orientation and stress in a flexible-chain polymer fluid subjected to steady biaxial extensional flow is analyzed. Closed-formula model based on the Padè approximation of the inverse Langevin function in the non-Gaussian distribution of the chain end-to-end vectors is considered. The approach is free from the limitations related to finite chain extensibility and slow convergence of the series expansion formulations at higher chain deformations.Segmental orientation is characterized by the average orientation tensor, related axial orientation factors and global orientation anisotropy. Orientational behavior and corresponding stresses in the biaxial elongational potential flow are discussed in a wide range of elongation rates. Orientation characteristics calculated for the biaxial flow deformation are much higher than those predicted for the affine biaxial stretch deformation in polymer solids.     

Reactive compatibilization and properties of recycled poly(ethylene terephthalate)/polyethylene blends

Summary Blends of recycled poly(ethylene terephthalate) (R-PET) and high-density polyethylene (R-PE), obtained from post-consumer packaging materials, were prepared both by melt mixing and extrusion processes and compatibilized by addition of various copolymers containing functional reactive groups, such as maleic anhydride, acrylic acid and glycidyl methacrylate. The effect of the type and concentration of compatibilizer, as well as the mixing conditions, on the phase morphology, thermal behaviour, rheological and mechanical properties of the blends was investigated. The results indicated that addition (5÷10 pph) of ethylene-co-glycidyl methacrylate copolymer (E-GMA) allows for a marked improvement of processability and physical/mechanical performances of R-PET/R-PE blends. Received: 1 March 2001/Revised version: 15 November 2001/ Accepted: 28 January 2002     

Alteration of substrate specificity of cholesterol oxidase from Streptomyces sp. by site-directed mutagenesis

Despite the structural similarities between cholesterol oxidasefrom Streptomyces and that from Brevibacterium, both enzymesexhibit different characteristics, such as catalytic activity,optimum pH and temperature. In attempts to define the molecularbasis of differences in catalytic activity or stability, substitutionsat six amino acid residues were introduced into cholesteroloxidase using site-directed mutagenesis of its gene. The aminoacid substitutions chosen were based on structural comparisonsof cholesterol oxidases from Streptomyces and Brevibacterium.Seven mutant enzymes were constructed with the following aminoacid substitutions: L117P, L119A, L119F, V145Q, Q286R, P357Nand S379T. All the mutant enzymes exhibited activity with theexception of that with the L117P mutation. The resulting V145Qmutant enzyme has low activities for all substrates examinedand the S379T mutant enzyme showed markedly altered substratespecificity compared with the wild-type enzyme. To evaluatethe role of V145 and S379 residues in the reaction, mutantswith two additional substitutions in V145 and four in S379 wereconstructed. The mutant enzymes created by the replacement ofV145 by Asp and Glu had much lower catalytic efficiency forcholesterol and pregnenolone as substrates than the wild-typeenzyme. From previous studies and this study, the V145 residueseems to be important for the stability and substrate bindingof the cholesterol oxidase. In contrast, the catalytic efficiencies(k_cat/K_m) of the S379T mutant enzyme for cholesterol and pregnenolonewere 1.8- and 6.0-fold higher, respectively, than those of thewild-type enzyme. The enhanced catalytic efficiency of the S379Tmutant enzyme for pregnenolone was due to a slightly high k_catvalue and a low K_m value. These findings will provide severalideas for the design of more powerful enzymes that can be appliedto clinical determination of serum cholesterol levels and assterol probes.     

Studies on curing urethane prepolymers with aniline–formaldehyde resins

Commercial aniline–cresol–formaldehyde resin, two model aniline–formaldehyde and aniline–cresol–formaldehyde resins, and methylenedianiline have been used as curatives for NCO-terminated urethane prepolymer prepared from polyoxypropylenediol and toluene-diisocyanate. Based on viscoelastic behavior of the investigated systems and changes in their IR spectra, it has been concluded that phenolic OH groups present in aniline–cresol–formaldehyde resin do not play an important role in the curing process carried out at RT despite earlier suggestions to the contrary. The explanation for specific behavior of systems where urethane prepolymers have been cured with commercial aniline–cresol–formaldehyde resin is presumably the presence of small amount of solvent (benzyl alcohol) in that resin, which may influence the reaction kinetics.