Mechanical Properties of Base-Modified DNA Are Not Strictly Determined by Base Stacking or Electrostatic Interactions

This work probes the mystery of what balance of forces creates the extraordinary mechanical stiffness of DNA to bending and twisting. Here we explore the relationship between base stacking, functional group occupancy of the DNA minor and major grooves, and DNA mechanical properties. We study double-helical DNA molecules substituting either inosine for guanosine or 2,6-diaminopurine for adenine. These DNA variants, respectively, remove or add an amino group from the DNA minor groove, with corresponding changes in hydrogen-bonding and base stacking energy. Using the techniques of ligase-catalyzed cyclization kinetics, atomic force microscopy, and force spectroscopy with optical tweezers, we show that these DNA variants have bending persistence lengths within the range of values reported for sequence-dependent variation of the natural DNA bases. Comparison with seven additional DNA variants that modify the DNA major groove reveals that DNA bending stiffness is not correlated with base stacking energy or groove occupancy. Data from circular dichroism spectroscopy indicate that base analog substitution can alter DNA helical geometry, suggesting a complex relationship among base stacking, groove occupancy, helical structure, and DNA bend stiffness.     

Fermented Hass avocado kernel: Nutritional properties and use in the manufacture of biscuits

In this study, the use of fermented Hass avocado kernel (FHK) with Lactobacillus plantarum to produce functional biscuits was examined. The chemical composition and antinutrient factors were evaluated for raw and fermented Hass avocado kernels. Fatty acids were separated by gas liquid chromatography. The physical properties, color, and sensory attributes of the biscuits were assessed using professional methods. The protein increased by 54% after fermentation to become (7.93%) in FHK while it was 5.15% in raw Hass avocado kernel (RHK). The crude fiber and ash decreased after fermentation by 18% and 8%, respectively. A significant (p < 0.05) increase was recorded in total phenol content, antiradical effect against DPPH and flavonoid content of FHK compared with RHK. After fermentation, reduction of tannins content was 80.76%, oxalates content 89.95%, alkaloids 70%, while traces of phytates and saponin were detected. The relative density, saponification value and iodine value of FHK oil were 0.917 g/ml, 212.26 mg KOH/g oil and 72.74 g Iodine/100 g oil, respectively. FHK oil had the following sequence: PUFA (51.54%) > SFA (26.72%) > MUFA (21.83%). The highest spread ratio (6.17) was recorded in biscuits produced by replacing 10% of FHK. Difference between the biscuit samples in the color from all treatments was completely compatible with the sensory evaluation results. Substituting 5% and 10% of FHK flour significantly improved both the brittleness and the total percentage of replacement.     

Benzoxazole derivatives as new VEGFR-2 inhibitors and apoptosis inducers: design,synthesis, in silico studies,and antiproliferative evaluation

In this study, a set of novel benzoxazole derivatives were designed, synthesised, and biologically evaluated as potential VEGFR-2 inhibitors. Five compounds (12d, 12f, 12i, 12l, and 13a) displayed high growth inhibitory activities against HepG2 and MCF-7 cell lines and were further investigated for their VEGFR-2 inhibitory activities. The most potent anti-proliferative member 12 l (IC₅₀ = 10.50 μM and 15.21 μM against HepG2 and MCF-7, respectively) had the most promising VEGFR-2 inhibitory activity (IC₅₀ = 97.38 nM). A further biological evaluation revealed that compound 12l could arrest the HepG2 cell growth mainly at the Pre-G1 and G1 phases. Furthermore, compound 12l could induce apoptosis in HepG2 cells by 35.13%. likely, compound 12l exhibited a significant elevation in caspase-3 level (2.98-fold) and BAX (3.40-fold), and a significant reduction in Bcl-2 level (2.12-fold). Finally, docking studies indicated that 12l exhibited interactions with the key amino acids in a similar way to sorafenib.     

Design,synthesis, and anti-cancer evaluation of new pyrido[2,3-d]pyrimidin-4(3H)-one derivatives as potential EGFRWT and EGFRT790M inhibitors and apoptosis inducers

A new series of pyrido[2,3-d]pyrimidin-4(3H)-one derivatives having the essential pharmacophoric features of EGFR inhibitors has been designed and synthesised. Cell viability screening was performed for these compounds against A-549, PC-3, HCT-116, and MCF-7 cell lines at a dose of 100 μM. The highest active derivatives (8a, 8 b, 8d, 9a, and 12b) were selected for IC₅₀ screening. Compounds 8a, 8 b, and 9a showed the highest cytotoxic activities and were further investigated for wild EGFR^WT and mutant EGFR^T790M inhibitory activities. Compound 8a showed the highest inhibitory activities against EGFR^WT and EGFR^T790M with IC₅₀ values of 0.099 and 0.123 µM, respectively. In addition, it arrested the cell cycle at pre-G1 phase and induced a significant apoptotic effect in PC-3 cells. Furthermore, compound 8a induced a 5.3-fold increase in the level of caspase-3 in PC-3 cells. Finally, docking studies were carried out to examine the binding mode of the synthesised compounds against both EGFR^WT and EGFR^T790M.     

Pyrolysis of triglyceride materials for the production of renewable fuels and chemicals

Conversion of vegetable oils and animal fats composed predominantly of triglycerides using pyrolysis type reactions represents a promising option for the production of renewable fuels and chemicals. The purpose of this article was to collect and review literature on the thermo-chemical conversion of triglyceride based materials. The literature was divided and discussed as (1) direct thermal cracking and (2) combination of thermal and catalytic cracking. Typically, four main catalyst types are used including transition metal catalysts, molecular sieve type catalysts, activated alumina, and sodium carbonate. Reaction products are heavily dependant on the catalyst type and reaction conditions and can range from diesel like fractions to gasoline like fractions. Research in this area is not as advanced as bio-oil and bio-diesel research and there is opportunity for further study in the areas of reaction optimization, detailed characterization of products and properties, and scale-up.     

Glutathione reductase from Lactobacillus sanfranciscensis DSM20451T: contribution to oxygen tolerance and thiol exchange reactions in wheat sourdoughs

The effect of the glutathione reductase (GshR) activity of Lactobacillus sanfranciscensis DSM20451(T) on the thiol levels in fermented sourdoughs was determined, and the oxygen tolerance of the strain was also determined. The gshR gene coding for a putative GshR was sequenced and inactivated by single-crossover integration to yield strain L. sanfranciscensis DSM20451(T)DeltagshR. The gene disruption was verified by sequencing the truncated gshR and surrounding regions on the chromosome. The gshR activity of L. sanfranciscensis DSM20451(T)DeltagshR was strongly reduced compared to that of the wild-type strain, demonstrating that gshR indeed encodes an active GshR enzyme. The thiol levels in wheat doughs fermented with L. sanfranciscensis DSM20451 increased from 9 microM to 10.5 microM sulfhydryl/g of dough during a 24-h sourdough fermentation, but in sourdoughs fermented with L. sanfranciscensis DSM20451(T)DeltagshR and in chemically acidified doughs, the thiol levels decreased to 6.5 to 6.8 microM sulfhydryl/g of dough. Remarkably, the GshR-negative strains Lactobacillus pontis LTH2587 and Lactobacillus reuteri BR11 exerted effects on thiol levels in dough comparable to those of L. sanfranciscensis. In addition to the effect on thiol levels in sourdough, the loss of GshR activity in L. sanfranciscensis DSM20451(T)DeltagshR resulted in a loss of oxygen tolerance. The gshR mutant strain exhibited a strongly decreased aerobic growth rate on modified MRS medium compared to either the growth rate under anaerobic conditions or that of the wild-type strain, and aerobic growth was restored by the addition of cysteine. Moreover, the gshR mutant strain was more sensitive to the superoxide-generating agent paraquat.     

Approximate Joint Diagonalization and Geometric Mean of Symmetric Positive Definite Matrices

We explore the connection between two problems that have arisen independently in the signal processing and related fields: the estimation of the geometric mean of a set of symmetric positive definite (SPD) matrices and their approximate joint diagonalization (AJD). Today there is a considerable interest in estimating the geometric mean of a SPD matrix set in the manifold of SPD matrices endowed with the Fisher information metric. The resulting mean has several important invariance properties and has proven very useful in diverse engineering applications such as biomedical and image data processing. While for two SPD matrices the mean has an algebraic closed form solution, for a set of more than two SPD matrices it can only be estimated by iterative algorithms. However, none of the existing iterative algorithms feature at the same time fast convergence, low computational complexity per iteration and guarantee of convergence. For this reason, recently other definitions of geometric mean based on symmetric divergence measures, such as the Bhattacharyya divergence, have been considered. The resulting means, although possibly useful in practice, do not satisfy all desirable invariance properties. In this paper we consider geometric means of covariance matrices estimated on high-dimensional time-series, assuming that the data is generated according to an instantaneous mixing model, which is very common in signal processing. We show that in these circumstances we can approximate the Fisher information geometric mean by employing an efficient AJD algorithm. Our approximation is in general much closer to the Fisher information geometric mean as compared to its competitors and verifies many invariance properties. Furthermore, convergence is guaranteed, the computational complexity is low and the convergence rate is quadratic. The accuracy of this new geometric mean approximation is demonstrated by means of simulations.     

Vital Parameters Assessments of Starvation Tolerance of <i>in vitro Populus alba</i> Culture

Populus alba is a large woody deciduous plant. The plant has been introduced to shooting, then multiplication of rooting on Murashige and Skoog (MS) medium. This work was designed to estimate the effect of two factors (low levels of 1-Naphthaleneacetic acid NAA and sucrose) on P. alba response resulting in 6 treatments compared to the control, with twelve measured responses. There was a significant difference in some measurements in morphology, like plantlets fresh-weight, shoot-, root-length, and leaf number. In the physiological measurements, there were significant differences in all the measured parameters. The low concentrations of sucrose and media composition/power (MS grams/L) led to starvation in plants; however, these conditions led to enhancement in some morphological and physiological parameters to overcome the starvation effect, compared to the control. The RAPD-PCR molecular marker (four decamers) was used to evaluate the new individuals’ genetic variation (instability), resulting in a total polymorphism percentage of 50.83%. It was formerly known that the plantlets were identical to each other and to the mother plant. In this study, however, the use of distinct media power, hormonal and sucrose levels resulted in molecular variation reflected in P. alba’s morphological and physiological responses.