Design, synthesis, and biological activity of hydroxamic tertiary amines as histone deacetylase inhibitors

Herein we describe the design, synthesis, and biological evaluation of new hydroxamic tertiary amines as histone deacetylase (HDAC) inhibitors. These compounds have allowed us to clarify the influence of cap group dimension and hydrophobicity on HDAC inhibitory activity. This report also reveals the recognition pattern between the linear compounds and the histone deacetylase-like protein (HDLP) model receptor, and discusses the synthesis and in vitro evaluation of HDAC inhibitory activity in HeLa cell nuclear extracts. We obtained good qualitative agreement between experimental results and theoretical predictions, confirming that appropriately substituted hydroxamic tertiary amines are potential active HDAC inhibitors.     

Improvement of bread quality and bread shelf-life by Bacillus subtilis biosurfactant addition

The objective of the present work was to determine the effect of the addition of a microorganism derived emulsifier on the quality of bread. The effect of Bacillus subtilis SPB1 biosurfactant has been investigated in comparison to a commercial surfactant, the soya lecithin. Indeed, it led to a better shape and a greater specific volume and voided fraction of loaves. Also, results showed that SPB1 bioemulsifier addition improved considerably the texture profile of bread, mainly at a concentration of 0.075%(w/w). In fact, we showed a notable decrease of firmness, chewiness, and adhesion values with a slight increase of cohesion for bread added emulsifier. According to crumb texture evolution during storage, SPB1 biosurfactant exhibited a significant antistaling effect. Moreover, SPB1 biosurfactant addition reduced significantly bread susceptibility to microbial contamination. These results proved that SPB1 biosurfactant could be of a great interest in the bread-making industry.     

Reduction of fume and gas emissions using innovative gas metal arc welding variants

New environmental, health and safety legislation, both in the EU and in the USA, is driving the need for the study of new welding processes, and the selection of the operational procedures that will reduce fume emissions and will promote a healthier, safer and more productive work environment. Actually, there are a significant number of publications related with gas metal arc welding hazards. However, for the new gas metal arc welding hazards variants, especially cold metal transfer, there is no data available concerning fumes and gases emissions. This paper attempts to point out ways of reducing the harmful effects of gas metal arc welding processes using different filler materials, different shielding gases, different operational welding procedures and three welding processes: gas metal arc welding process and two variants, pulsed gas metal arc welding and cold metal transfer. The effect of nitrogen oxide addition to the shielding gas composition on the amount of welding fumes and gaseous emissions produced during welding is also analysed. The amount of fume and gases generated during welding was measured over a range of current intensity and arc voltages, using the standard procedures contained in EN ISO 15011-2 [1]. The data presented give a summary of the different gas metal arc welding variants and their relations to fume generation rates and gases emitted. The results obtained give indications on measures to be taken in order to reduce fume and gas emissions. In general, the minimisation of fume formation rate can be achieved by using lower energy gas metal arc welding variants, gas shielding with low CO₂ and O₂ contents and “green” wires.     

ZnO micro and nanocrystals with enhanced visible light absorption

In this paper, we investigate the effect of the particle size and morphology on the optical properties of ZnO. A series of ZnO micro and nanocrystals were synthesized by the hydrothermal processing of zinc acetate dihydrate and sodium hydroxide as the starting materials, and polyvinylpyrrolidone (PVP) as the polymer surfactant. The particle size and morphology were tailored by adjusting the reactant molar ratios [Zn²⁺]/[OH⁻], while the reaction temperature and the time remained unchanged. X-ray diffraction (XRD), transmission electron microscopy (TEM), selected area electron diffraction (SAED) and high-resolution TEM (HRTEM) have shown that the micro and nanocrystals have a high crystalline pure wurtzite-type hexagonal structure with nanosized crystallites. The size and morphology of the ZnO micro and nanocrystals were investigated by field emission scanning electron microscopy (FE-SEM), which showed a modification from micro-rods via hexagonal-faceted prismatic morphology to nanospheres, caused by simple adjustment of the reactant molar ratio [Zn²⁺]/[OH⁻] from 1:1 to 1:5. The optical properties of the ZnO micro and nanocrystals, as well as their dependence on the particle size and morphology were investigated by Raman and ultraviolet–visible (UV–vis) diffuse reflectance spectroscopy (DRS). The UV–vis spectra showed that the modification of the particle size and morphology from nanospheres to micro-rods resulted in increased absorption, and a slight red-shift of the absorption edge (0.06 eV). Besides, the band gap energy of the synthesized ZnO micro and nanocrystals showed the red shift (∼0.20 eV) compared to bulk ZnO. According to the results of a Raman spectroscopy, the enhanced visible light absorption of the ZnO micro and nanocrystals is related to two phenomena: (1) the existence of lattice defects (oxygen vacancies and zinc interstitials), and (2) the particle surface sensitization by PVP.     

Renal Dopamine Receptors,Oxidative Stress,and Hypertension

Dopamine, which is synthesized in the kidney, independent of renal nerves, plays an important role in the regulation of fluid and electrolyte balance and systemic blood pressure. Lack of any of the five dopamine receptor subtypes (D1R, D2R, D3R, D4R, and D5R) results in hypertension. D1R, D2R, and D5R have been reported to be important in the maintenance of a normal redox balance. In the kidney, the antioxidant effects of these receptors are caused by direct and indirect inhibition of pro-oxidant enzymes, specifically, nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) oxidase, and stimulation of anti-oxidant enzymes, which can also indirectly inhibit NADPH oxidase activity. Thus, stimulation of the D2R increases the expression of endogenous anti-oxidants, such as Parkinson protein 7 (PARK7 or DJ-1), paraoxonase 2 (PON2), and heme oxygenase 2 (HO-2), all of which can inhibit NADPH oxidase activity. The D5R decreases NADPH oxidase activity, via the inhibition of phospholipase D2, and increases the expression of HO-1, another antioxidant. D1R inhibits NADPH oxidase activity via protein kinase A and protein kinase C cross-talk. In this review, we provide an overview of the protective roles of a specific dopamine receptor subtype on renal oxidative stress, the different mechanisms involved in this effect, and the role of oxidative stress and impairment of dopamine receptor function in the hypertension that arises from the genetic ablation of a specific dopamine receptor gene in mice.     

Evidence for the combined participation of a C10 and a C15 precursor in the biosynthesis of moenocinol, the lipid part of the moenomycin antibiotics

Upon feeding of [2-(13)C,4-(2)H]-1-deoxy-D-xylulose to Streptomyces ghanaensis, the deuterium label was retained exclusively at positions C-7 and C-17 in the moenocinol part of the moenomycin antibiotics. This result vindicates the hypothesis that the C(25) structure of moenocinol is assembled from a C(10) and a C(15) precursor, each of which requires for its formation the involvement of a dimethylallyl diphosphate starter unit.     

Practical exponential stability of perturbed triangular systems and a separation principle

In this paper, we present a practical stability result for perturbed dynamic systems depending on a parameter and we study the practical exponential stability of perturbed triangular systems. These results are applied to show that a separation principle for nonlinear uncertain systems can be achieved and which considers practical global uniform exponential stability. Copyright © 2010 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society     

Effect of inorganic and organic bioactive signals decoration on the biological performance of chitosan scaffolds for bone tissue engineering

The present work is focused on the design of a bioactive chitosan-based scaffold functionalized with organic and inorganic signals to provide the biochemical cues for promoting stem cell osteogenic commitment. The first approach is based on the use of a sequence of 20 amino acids corresponding to a 68–87 sequence in knuckle epitope of BMP-2 that was coupled covalently to the carboxyl group of chitosan scaffold. Meanwhile, the second approach is based on the biomimetic treatment, which allows the formation of hydroxyapatite nuclei on the scaffold surface. Both scaffolds bioactivated with organic and inorganic signals induce higher expression of an early marker of osteogenic differentiation (ALP) than the neat scaffolds after 3 days of cell culture. However, scaffolds decorated with BMP-mimicking peptide show higher values of ALP than the biomineralized one. Nevertheless, the biomineralized scaffolds showed better cellular behaviour than neat scaffolds, demonstrating the good effect of hydroxyapatite deposits on hMSC osteogenic differentiation. At long incubation time no significant difference among the biomineralized and BMP-activated scaffolds was observed. Furthermore, the highest level of Osteocalcin expression (OCN) was observed for scaffold with BMP2 mimic-peptide at day 21. The overall results showed that the presence of bioactive signals on the scaffold surface allows an osteoinductive effect on hMSC in a basal medium, making the modified chitosan scaffolds a promising candidate for bone tissue regeneration.     

The impact of education and cooking methods on serum phosphate levels in patients on hemodialysis: 1‐year study

Introduction: Control of serum phosphate is important for patients on hemodialysis. The aim of the study was to determine if education based on phosphorus‐reducing techniques in food preparation and thermal processing, and accordingly prepared and applied diets, will lead to better outcomes than a standard education program to improve phosphate control in patients on hemodialysis. Methods: Forty‐seven patients on hemodialysis were divided between an intervention and a control group. All subjects received training about nutrition for hemodialysis patients by trained dietitian. In addition, subjects in the intervention group received additional training in phosphorus‐reducing techniques in food preparation and received two hospital meals prepared using suggested cooking methods to reduce the phosphate content of food during dialysis treatment. Serum phosphate, serum albumin, and anthropometric parameters were measured, while nPCR was calculated, at the baseline and during the 1‐year study. Findings: No differences in serum phosphate levels were observed between intervention (1.68 mmol/L [1.48–2.03]) and control group (1.88 mmol/L [1.57–2.2]) at baseline (P = 0.130). Although not statistically significant between groups the mean reduction was more apparent in the intervention group (?0.3 mmol/L (?0.4 to 0.1) vs. ?0.2 (?0.5 to 0.1)), and lead to significantly reduction of phosphate binder therapy. During the study, the nPCR and anthropometric status of the patients did not change significantly. Discussion: Providing additional education to hemodialysis patients on the specific cooking methods and accordingly prepared meals may decrease serum phosphate levels without significantly affecting nutritional status which may be useful in helping to prevent and treat hyperphosphatemia.