Dietary Omega-3 Fatty Acids Prevented Adipocyte Hypertrophy by Downregulating DGAT-2 and FABP-4 in a Sex-Dependent Fashion

Obesity is characterized by an increase in fat mass primarily as a result of adipocyte hypertrophy. Diets enriched in omega (n)‐3 polyunsaturated fatty acids (PUFA) are suggested to reduce obesity, however, the mechanisms are not well understood. We investigated the effect of n‐3 PUFA on adipocyte hypertrophy and the key genes involved in adipocyte hypertrophy. Female C57BL/6 mice were fed semi‐purified diets (20 % w/w fat) containing high n‐3 PUFA before mating, during pregnancy, and until weaning. Male and female offspring were continued on high n‐3 PUFA (10 % w/w), medium n‐3 PUFA (4 % w/w), or low n‐3 PUFA (2 % w/w) diet for 16 weeks postweaning. Adipocyte area was quantified using microscopy, and gonadal mRNA expression of acyl CoA:diacylglycerol acyltransferase‐2 (DGAT‐2), fatty acid binding protein‐4 (FABP‐4) and leptin were measured. The high n‐3 PUFA group showed higher levels of total n‐3 PUFA in gonadal TAG compared to the medium and low n‐3 PUFA groups (P < 0.001). The high n‐3 PUFA male group had a lower adipocyte area compared to the medium and low n‐3 PUFA group (P < 0.001); however, no difference was observed in females. The high n‐3 PUFA male group showed lower mRNA expression of FABP‐4, DGAT‐2 and leptin compared to the low n‐3 PUFA group, with no difference in females. Plasma lipid levels were lower in the high n‐3 PUFA group compared to the other groups. Our findings show for the first time that n‐3 PUFA prevents adipocyte hypertrophy by downregulating FABP‐4, DGAT‐2 and leptin; the effects are however sex‐specific.     

Mechanical properties of natural fiber hybrid composites based on renewable thermoset resins derived from soybean oil,for use in technical applications

Natural fiber composites are known to have lower mechanical properties than glass or carbon fiber reinforced composites. The hybrid natural fiber composites prepared in this study have relatively good mechanical properties. Different combinations of woven and non‐woven flax fibers were used. The stacking sequence of the fibers was in different orientations, such as 0°, +45°, and 90°. The composites manufactured had good mechanical properties. A tensile strength of about 119 MPa and Young's modulus of about 14 GPa was achieved, with flexural strength and modulus of about 201 MPa and 24 GPa, respectively. For the purposes of comparison, composites were made with a combination of woven fabrics and glass fibers. One ply of a glass fiber mat was sandwiched in the mid‐plane and this increased the tensile strength considerably to 168 MPa. Dynamic mechanical analysis was performed in order to determine the storage and loss modulus and the glass transition temperature of the composites. Microstructural analysis was done with scanning electron microscopy. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

A program for individual and population optimal design for univariate and multivariate response pharmacokinetic-pharmacodynamic models

The design of pharmacokinetic and pharmacodynamic experiments concerns a number of issues, among which are the number of observations and the times when they are taken. Often a model is used to describe these data and the pharmacokinetic-pharmacodynamic behavior of a drug. Knowledge of the data analysis model at the design stage is beneficial for collecting patient data for parameter estimation. A number of criteria for model-oriented experiments, which maximize the information content of the data, are available. In this paper we present a program, Popdes, to investigate the D-optimal design of individual and population multivariate response models, such as pharmacokinetic-pharmacodynamic, physiologically based pharmacokinetic, and parent drug and metabolites models. A pre-clinical and clinical pharmacokinetic-pharmacodynamic model describing the concentration-time profile and effect of an oncology compound in development is used for illustration.     

Forced cycling of the catalytic oxidation of CO over a V2O5 catalyst—II Temperature cycling

An experimental study was made of the effects of temperature cycling on carbon monoxide oxidation over a vanadium pentoxide catalyst. Square-wave temperature cycles at periods above 5 hr provided reaction rates which, when time-averaged, were closely approximated by quasi-steady state reaction rates. As the period decreases, reaction rates fall off indicating that time-average rates under transient conditions are lower than those acheived at quasi-steady state. At a period of one hour, the time-average cycling rate falls below the rate at steady state at the mean temperature of the cycle used.     

Functional properties and retrogradation behaviour of native and chemically modified starch of mucuna bean (Mucuna pruriens)

Mucuna bean (Mucuna pruriens) starch was isolated and subjected to chemical modification by oxidation and acetylation. The proximate analysis of the non‐starch components of the native starch on a dry weight basis was 92 g kg^?1 moisture, 5 g kg^?1 ash, 2 g kg^?1 fat, 7 g kg^?1 crude fibre and 19 g kg^?1 protein. Chemical modification reduced the values for all the non‐starch components except the moisture level. For all the samples, swelling power and solubility increased as the temperature increased in the range 50–90 °C. The swelling power of mucuna native starch (MNS) and mucuna acetylated starch (MAS) increased with increasing acidity and alkalinity, while that of mucuna oxidised starch (MOS) only increased with increasing pH in the acidic range. The maximal solubility of all the starches was observed at pH 12. All the starch samples absorbed more oil than water. The lowest gelation concentration followed the trend MAS < MNS < MOS. Chemical modification reduced the gelatinisation temperature (Tp), while peak viscosity (Pv), hot paste viscosity (Hv) and cold paste viscosity (Cv) decreased after oxidation but increased following acetylation. The setback tendency of the native starch was reduced significantly after chemical modification. However, the breakdown value of MNS, 65 BU (Brabender units), was lower than that of MOS (78 BU) but higher than that of MAS (40 BU). Differential scanning calorimetry studies of gelatinisation and retrogradation revealed that chemical modification reduced the onset temperature (T_o), peak temperature (T_p) and conclusion temperature (T_c). Oxidation and acetylation reduced the gelatinisation and retrogradation enthalpies of the native starch. The enthalpy of retrogradation of the starches increased as the length of storage increased. Copyright © 2003 Society of Chemical Industry     

From On‐Target to Off‐Target Activity: Identification and Optimisation of Trypanosoma brucei GSK3 Inhibitors and Their Characterisation as Anti‐Trypanosoma brucei Drug Discovery Lead Molecules

Human African trypanosomiasis (HAT) is a life‐threatening disease with approximately 30 000–40 000 new cases each year. Trypanosoma brucei protein kinase GSK3 short (TbGSK3) is required for parasite growth and survival. Herein we report a screen of a focused kinase library against T. brucei GSK3. From this we identified a series of several highly ligand‐efficient TbGSK3 inhibitors. Following the hit validation process, we optimised a series of diaminothiazoles, identifying low‐nanomolar inhibitors of TbGSK3 that are potent in vitro inhibitors of T. brucei proliferation. We show that the TbGSK3 pharmacophore overlaps with that of one or more additional molecular targets.     

Parametric studies of mixed convective fluid flow around cylinders of different cross-sections

A numerical study of mixed convective heat transfer in a lid-driven square enclosure containing a hot elliptic cylinder is conducted. The impacts of the Grashof number $({10}^3\le \mathit{Gr}\le 10^6)$, Reynolds number $(1.0\le Re\le 100)$, cylinder tilt angle $(0^{°}\le \varphi \le {90}^{°})$, and aspect ratio $(1.0\le AR\le 3.0)$ have been examined for a fluid of $Pr$ of 0.71. The horizontal enclosure walls are insulated, while its vertical walls are restricted to a nonvarying temperature T_c, whereas a sinusoidal temperature of $T_h+∆T\sin (\pi x/L)$ is imposed on the wall of the elliptical cylinder. The governing equations are solved using COMSOL Multiphysics 5.6 software. The fluid dynamic and the heat transport profiles between the enclosure and the elliptical cylinder walls are represented by the stream function, isothermal contours, and average Nusselt number. Results established that for all the considered aspect ratios, the thermal heating range of ${10}^3\le \mathit{Gr}\le 10^4$ is predominantly a conduction mechanism. The critical position of the ellipse where the inclination effect becomes insignificant is determined by the Grashof number and aspect ratio when the Re = 100. The strength of vortices and cell numbers are significantly influenced by the aspect ratio, particularly when the $\mathit{Gr}=10^4$. When $AR=1.0$, the average heat transfer from the cylinder remains the same regardless of the cylinder's orientation. The impact of cylinder orientation on heat transfer from the cylinder wall is minimal for $1.5\le AR\le 2.0$. For AR values of $2.5\le AR\le 3.0$, increasing the inclination angle does not result in improved heat transfer. The influence of the increasing inclination angle on the right wall diminishes as the angle increases, except when the Grashof number is greater than 10⁵, where the rate of heat transfer is enhanced for inclination angles beyond 45°.