GCN5-related N-acetyltransferase (GNAT) is a huge superfamily of proteins spanning the prokaryotic and eukaryotic domains of life. GNAT proteins usually transfer an acetyl group from acetyl-CoA to a wide variety of substrates ranging from aminoglycoside antibiotics to large macromolecules. Type II toxin-antitoxin (TA) modules are typically bicistronic and widespread in bacterial and archael genomes with diverse cellular functions. Recently, a novel family of type II TA toxins was described, which presents a GNAT-fold and functions by acetylating charged tRNA thereby precluding translation. These GNAT toxins are usually associated with a corresponding ribbon-helix-helix-fold (RHH) antitoxin. In this issue, Qian et al. describes a unique GNAT-RHH TA system, designated KacAT, from a multidrug resistant strain of the pathogen, Klebsiella pneumoniae. As most type II TA loci, kacAT is transcriptionally autoregulated with the KacAT complex binding to the operator site via the N-terminus region of KacA to repress kacAT transcription. The crystal structure of the KacT toxin is also presented giving a structural basis for KacT toxicity. These findings expand our knowledge on this newly discovered family of TA toxins and the potential role that they may play in antibiotic tolerance and persistence of bacterial pathogens.
In this study, an optimized mesoporous sulfonated carbon (OMSC) catalyst derived from palm kernel shell biomass was developed using template carbonization and subsequent sulfonation under different temperatures and time conditions. The OMSC catalyst was characterized using acid-base titration, elemental analysis, XRD, Raman, FTIR, XPS, TPD-NH3, TGA-DTA, SEM, and N2 adsorption-desorption analysis to reveal its properties. Results proved that the OMSC catalyst is mesoporous and amorphous in structure with improved textural, acidic, and thermal properties. Both FTIR and XPS confirmed the presence of -SO3H, -OH, and -COOH functional groups on the surface of the catalyst. The OMSC catalyst was found to be efficient in catalyzing glycerol conversion to acetin via an acetylation reaction with acetic acid within a short period of 3 h. Response surface methodology (RSM), based on a two-level, three-factor, face-centered central composite design, was used to optimize the reaction conditions. The results showed that the optimized temperature, glycerol-to-acetic acid mole ratio, and catalyst load were 126 °C, 1:10.4, and 0.45 g, respectively. Under these optimum conditions, 97% glycerol conversion (GC) and selectivities of 4.9, 27.8, and 66.5% monoacetin (MA), diacetin (DA), and triacetin (TA), respectively, were achieved and found to be close to the predicted values. Statistical analysis showed that the regression model, as well as the model terms, were significant with the predicted R2 in reasonable agreement with the adjusted R2 (<0.2). The OMSC catalyst maintained excellent performance in GC for the five reaction cycles. The selectivity to TA, the most valuable product, was not stable until the fourth cycle, attributable to the leaching of the acid sites.
Histone acetylation plays an important role in regulation of transcription in eukaryotic cells by promoting a more relaxed chromatin structure necessary for transcriptional activation. Histone deacetylases (HDACs) remove acetyl groups and suppress gene expression. HDAC inhibitors (HDACIs) are a group of small molecules that promote gene transcription by chromatin remodeling and have been extensively studied as potential drugs for treating of spinal muscular atrophy. Various drugs in this class have been studied with regard to their efficacy in increasing the expression of survival of motor neuron (SMN) protein. In this review, we discuss the current literature on this topic and summarize the findings of the main studies in this field.
Detail chemical studies on Carcinia maingayi have yielded one xanthone, 1,3,7-trihydroxy-2-(3-methylbut-2-enyl)-xanthone, one benzophenone, isoxanthochymol, one benzoic acid derivative 3,4-dihydroxy-methylbenzoate and two triterpenoids, stigmasterol and sitosterol. Meanwhile, investigations on Carcinia parvifolia have afforded one triterpenoid, a-amyrin and two xanthones, cowanin and rubraxanthone. Their structures were derived based on spectroscopic evidence, mainly ID and 2D NMR spectroscopy. Acetylation reaction was carried out on rubraxanthone to yield triacetate rubraxanthone. It was found that the pure rubraxanthone was strongly active against the larvae of Aedes aegypti with LC50 value of 15.49 {lg/ ml and HL-60 cells line with an IC50 value of 7.5 {lg/ ml.
Studies have suggested that sirtuin inhibition may have beneficial effects on several age-related diseases such as neurodegenerative disorders and cancer. Garcinia mangostana is a well-known tropical plant found mostly in South East Asia with several positive health effects. Some of its phytochemicals such as α-mangostin was found to be able to modulate sirtuin activity in mice and was implicated with inflammation, diabetes and obesity. However, comprehensive studies on sirtuin activity by the prenylated xanthones extracted from Garcinia mangostana have yet to be reported. The present study led to the discovery and identification of γ-mangostin as a potent and selective SIRT2 inhibitor. It was demonstrated that γ-mangostin was able to increase the α-tubulin acetylation in MDA-MD-231 and MCF-7 breast cancer cells. It was also found to possess potent antiproliferative activity against both cell lines. In addition, it was able to induce neurite outgrowth in the N2a cells.
In this study, effect of degree of deacetylation on property and adsorption capacity of chitosan/polyvinyl Alcohol electrospun membrane has been investigated. Resulting nanofibers were characterized by FESEM, FTIR, XRD, TGA, tensile testing, weight loss test and adsorption test. FESEM result shows, finer nanofiber was fabricated from 42h hydrolyzed chitosan and PVA blend solution. FTIR and XRD result showed a strong interaction between chitosan and polyvinyl alcohol. Higher tensile strength was observed for the nanofiber having 42h hydrolyzed chitosan. Blend solution of chitosan/PVA having low DD chitosan had higher viscosity. The nanofibrous membrane was stable in distilled water, acidic and basic medium. The isotherm study shows that the adsorption capacity (qm) of nanofiber containing higher DD chitosan was higher for Cr(VI). In contrary, the membrane containing chitosan with lower DD showed the higher adsorption capacity for Fe(III) and methyl orange. Moreover, the effect of DD on removal percentage of adsorbate was dependent on the initial concentration of the adsorbate.
Removal of oil spillage from the environment is a global concern. Various methods, including the use of fibers as sorbents, have been developed for oil spill control. Oil palm empty fruit bunch (OPEFB) fiber is a plant biomass that may be acetylated by acetic anhydride using N-bromosuccinimide (NBS) as a catalyst; here, the extent of acetylation may be calculated in terms of weight percent gain (WPG). The modified fiber was used to remove Tapis and Arabian crude oils. The optimum time, temperature, and catalyst concentration were 4 h, 120 °C, and 3 %, respectively, and these parameters could achieve an 11.49 % increase in WPG. The optimized parameters improved the adsorption capacity of OPEFB fibers for crude oil removal. The acetylated OPEFB fibers were characterized by using Fourier transform infrared spectroscopy and field emission scanning electron microscopy to observe the functional groups available and morphology. Kinetic and isotherm studies were conducted using different contact times and oil/water ratios. The rate of oil sorption onto the OPEFB fibers can be adequately described by the pseudo-second-order equation. Adsorption studies revealed that adsorption of crude oil on treated OPEFB fiber could be best described by the Langmuir isotherm model.
Recently, chitin and chitosan are widely investigated for food preservation and active packaging applications. Chemical, as well as biological methods, are usually adopted for the production of these biopolymers. In this study, modification to a chemical method of chitin synthesis from shrimp shells has been proposed through the application of high-frequency ultrasound. The impact of sonication time on the deproteinization step of chitin and chitosan preparation was examined. The chemical identities of chitin and chitosan were verified using infrared spectroscopy. The influence of ultrasound on the deacetylation degree, molecular weight and particle size of the biopolymer products was analysed. The microscopic characteristics, crystallinity and the colour characteristics of the as-obtained biopolymers were investigated. Application of ultrasound for the production of biopolymers reduced the protein content as well as the particle size of chitin. Chitosan of high deacetylation degree and medium molecular weight was produced through ultrasound assistance. Finally, the as-derived chitosan was applied for beef preservation. High values of luminosity, chromatid and chrome were noted for the beef samples preserved using chitosan films, which were obtained by employing biopolymer subjected to sonication for 15, 25 and 40 min. Notably; these characteristics were maintained even after ten days of packaging. The molecular weight of these samples are 73.61 KDa, 86.82 KDa and 55.66 KDa, while the deacetylation degree are 80.60%, 92.86% and 94.03%, respectively; in the same order, the particle size of chitosan are 35.70 μm, 25.51 μm and 20.10 μm.
Although acetylation is regarded as a common protein modification, a detailed proteome-wide profile of this post-translational modification may reveal important biological insight regarding differential acetylation of individual proteins. Here we optimized a novel peptide IEF fractionation method for use prior to LC-MS/MS analysis to obtain a more in depth coverage of N-terminally acetylated proteins from complex samples. Application of the method to the analysis of the serous ovarian cancer cell line OVCAR-5 identified 344 N-terminally acetylated proteins, 12 of which are previously unreported. The protein peptidyl-prolyl cis-trans isomerase A (PPIA) was detected in both the N-terminally acetylated and unmodified forms and was further analyzed by data-independent acquisition in carboplatin-responsive parental OVCAR-5 cells and carboplatin-resistant OVCAR-5 cells. This revealed a higher ratio of unacetylated to acetylated N-terminal PPIA in the parental compared with the carboplatin-resistant OVCAR-5 cells and a 4.1-fold increase in PPIA abundance overall in the parental cells relative to carboplatin-resistant OVCAR-5 cells (P = 0.015). In summary, the novel IEF peptide fractionation method presented here is robust, reproducible, and can be applied to the profiling of N-terminally acetylated proteins. All mass spectrometry data is available as a ProteomeXchange repository (PXD003547).
Nanofibrillated cellulose from biomass has recently gained attention owing to their biodegradable nature, low density, high mechanical properties, economic value and renewability. Although they still suffer from two major drawbacks. The first challenge is the exploration of raw materials and its application in nanocomposites production. Second one is high energy consumption regarding the mechanical fibrillation. However, pretreatments before mechanical isolation can overcome this problem. Hydrophilic nature of nano-size cellulose fibers restricts good dispersion of these materials in hydrophobic polymers and therefore, leads to lower mechanical properties. Surface modification before or after mechanical defibrillation could be a solution for this problem. Additionally, drying affects the size of nanofibers and its properties which needs to study further. This review focuses on recent developments in pretreatments, nanofibrillated cellulose production and its application in nanopaper applications, coating additives, security papers, food packaging, and surface modifications and also for first time its drying.
Different extraction conditions were applied to investigate the effect of temperature, extraction time and substrate-extractant ratio on pectin extraction from cocoa husks. Pectin was extracted from cocoa husks using water, citric acid at pH 2.5 or 4.0, or hydrochloric acid at pH 2.5 or 4.0. Temperature, extraction time and substrate-extractant ratio affected the yields, uronic acid contents, degrees of methylation (DM) and degrees of acetylation (DA) of the extracted pectins using the five extractants differently. The yields and uronic acid contents of the extracted pectins ranged from 3.38-7.62% to 31.19-65.20%, respectively. The DM and DA of the extracted pectins ranged from 7.17-57.86% to 1.01-3.48%, respectively. The highest yield of pectin (7.62%) was obtained using citric acid at pH 2.5 [1:25 (w/v)] at 95 °C for 3.0 h. The highest uronic acid content (65.20%) in the pectin was obtained using water [1:25 (w/v)] at 95 °C for 3.0 h.
Because chiral liquid chromatography (LC) could become a powerful tool to estimate racemic atenolol quantity, excellent enantiomeric separation should be produced during data acquisition for satisfactory observation of atenolol concentrations throughout the racemic resolution processes. Selection of chiral LC column and analytical protocol that fulfill demands of the ultra fast LC analysis is essential. This article describes the characteristics of atenolol chromatographic separation that resulted from different resolution media and analytical protocols with the use of a Chiralcel® OD column. The chromatograms showed quite different characteristics of the separation process. The single enantiomer and racemic atenolol could be recognized by the Chiralcel® OD column in less than 20 min. Symmetrical peaks were obtained; however, several protocols produced peaks with wide bases and slanted baselines. Observations showed that efficient enantioresolution of racemic atenolol was obtained at slow mobile phase flow rate, decreased concentration of amine-type modifier but increased alcohol content in mobile phase and highest ultraviolet detection wavelength were required. The optimal ultra fast LC protocol enables to reduce and eliminate the peaks of either the atenolol solvent or the buffers and provided the highest peak intensities of both atenolol enantiomers.
Oxygenated fuel additives can be produced by acetylation of glycerol. A 91% glycerol conversion with a selectivity of 38%, 28% and 34% for mono-, di- and triacetyl glyceride, respectively, was achieved at 120 °C and 3 h of reaction time in the presence of a catalyst derived from activated carbon (AC) treated with sulfuric acid at 85 °C for 4h to introduce acidic functionalities to its surface. The unique catalytic activity of the catalyst, AC-SA5, was attributed to the presence of sulfur containing functional groups on the AC surface, which enhanced the surface interaction between the glycerol molecule and acyl group of the acetic acid. The catalyst was reused in up to four consecutive batch runs and no significant decline of its initial activity was observed. The conversion and selectivity variation during the acetylation is attributed to the reaction time, reaction temperature, catalyst loading and glycerol to acetic acid molar ratio.
Acetone soluble oil palm empty fruit bunch cellulose acetate (OPEFB-CA) of DS 2.52 has been successfully synthesized in a one-step heterogeneous acetylation of OPEFB cellulose without necessitating the hydrolysis stage. This has only been made possible by the mathematical modeling of the acetylation process by manipulating the variables of reaction time and acetic anhydride/cellulose ratio (RR). The obtained model was verified by experimental data with an error of less than 2.5%. NMR analysis showed that the distribution of the acetyl moiety among the three OH groups of cellulose indicates a preference at the C6 position, followed by C3 and C2. XRD revealed that OPEFB-CA is highly amorphous with a degree of crystallinity estimated to be ca. 6.41% as determined from DSC. The OPEFB-CA films exhibited good mechanical properties being their tensile strength and Young's modulus higher than those of the commercial CA.
To investigate and compare the effect of three analytical methods, hydrogen bromide titrimetry (HBr titrimetry), infrared spectroscopy (IR spectroscopy), and first derivative UV-spectrophotometry (FDUV-spectrophotometry) in the determination of degree of deacetylation (DD) of chitosan.
An association of idiopathic systemic lupus erythematosus (ISLE) with genetically determined N-acetylation polymorphism has been suspected from previous studies, mainly on Caucasian populations in which there is an approximate incidence of 50% of slow and rapid acetylators. The present study is of the incidence of ISLE and acetylator status in a mixed population of Malaysia. The results did not support an association between ISLE and acetylator status: the frequencies of slow acetylators in the ISLE patients who were Malaysian Chinese and Malay were 13 and 38% respectively. This did not differ significantly from the respective healthy groups (20 and 29%). The small number of Indians in the survey did not allow a valid comparison, but the figures did suggest a lack of association between ISLE and acetylator status.
Ten new indole alkaloids, alstomaline (1), 10,11-dimethoxynareline (2), alstohentine (3), alstomicine (4), 16-hydroxyalstonisine (5), 16-hydroxyalstonal (6), 16-hydroxy-N(4)-demethylalstophyllal oxindole (7), alstophyllal (8), 6-oxoalstophylline (9), and 6-oxoalstophyllal (10), in addition to 21 other known ones, were obtained from the leaf extract of the Malayan Alstonia macrophylla. The structures were determined using NMR and MS analysis.
Epigenetic mechanisms involving the modulation of gene activity without modifying the DNA bases are reported to have lifelong effects on mature neurons in addition to their impact on synaptic plasticity and cognition. Histone methylation and acetylation are involved in synchronizing gene expression and protein function in neuronal cells. Studies have demonstrated in experimental models of neurodegenerative disorders that manipulations of these two mechanisms influence the susceptibility of neurons to degeneration and apoptosis. In Alzheimer's disease (AD), the expression of presenilin 1 (PSEN1) is markedly increased due to decreased methylation at CpG sites, thus promoting the accumulation of toxic amyloid-β (Aβ) peptide. In Parkinson's disease (PD), dysregulation of α-synuclein (SNCA) expression is presumed to occur via aberrant methylation at CpG sites, which controls the activation or suppression of protein expression. Mutant Huntingtin (mtHTT) alters the activity of histone acetyltransferases (HATs), causing the dysregulation of transcription observed in most Huntington's disease (HD) cases. Folate, vitamin B6, vitamin B12, and S-adenosylmethionine (SAM) are vital cofactors involved in DNA methylation modification; 5-azacytidine (AZA) is the most widely studied DNA methyltransferase (DNMT) inhibitor, and dietary polyphenols are DNMT inhibitors in vitro. Drug intervention is believed to reverse the epigenetic mechanisms to serve as a regulator in neuronal diseases. Nevertheless, the biochemical effect of the drugs on brain function and the underlying mechanisms are not well understood. This review focuses on further discussion of therapeutic targets, emphasizing the potential role of epigenetic factors including histone and DNA modifications in the diseases.
As part of a search for novel inhibitors of HIV-1 reverse transcriptase, the acetone extract of the giant African snail, Achatina fulica, was shown to be active. Fractionation of the extract yielded inophyllums A, B, C, and E and calophyllolide (1a, 2a, 3a, 3b, and 6), previously isolated from Calophyllum inophyllum Linn., a known source of nutrition for A. fulica. From a methanol/methylene chloride extract of C. inophyllum, the same natural products in considerably greater yield were isolated in addition to a novel enantiomer of soulattrolide (4), inophyllum P (2b), and two other novel compounds, inophyllums G-1 (7) and G-2 (8). The absolute stereochemistry of inophyllum A (1a) was determined to be 10(R), 11(S), 12(S) from a single-crystal X-ray analysis of its 4-bromobenzoate derivative, and the relative stereochemistries of the other inophyllums isolated from C. inophyllum were established by a comparison of their 1H NMR NOE values and coupling constants to those of inophyllum A (1a). Inophyllums B and P (2a and 2b) inhibited HIV reverse transcriptase with IC50 values of 38 and 130 nM, respectively, and both were active against HIV-1 in cell culture (IC50 of 1.4 and 1.6 microM). Closely related inophyllums A, C, D, and E, including calophyllic acids, were significantly less active or totally inactive, indicating certain structural requirements in the chromanol ring. Altogether, 11 compounds of the inophyllum class were isolated from C. inophyllum and are described together with the SAR of these novel anti-HIV compounds.
The aims of this study were to fabricate cellulose acetate (CA) film from oil palm empty fruit bunch (OP-EPB), as well as to characterize and evaluate their biocompatibility. Several processes were carried out, and these included prehydrolysis-soda method, chlorine free bleaching method, including oxygen, ozone and peroxide, to produce the cellulose pulp. Then, a liquid phase acetylation method was applied through acetic acid-acetic anhydride-sulphuric acid. Triethyl citrate (TEC) ester was used as additive at different percentages of 10, 20, 30 and 40 wt%. The film produced was characterized by FTIR to identify the functional group of the CA film and their tensile properties were further characterized. Biocompatibility of the film was evaluated using cytotoxicity test. Stem cell derived from human deciduous teeth (SHED) was used with MTS assay. The results showed at 30% of TEC, the tensile strength and elongation of CA (OP-EFB) film was at the optimum and is therefore suitable to be used in dental application. The cytotoxicity evaluated showed that the fabricated CA (OP-EFB) films were non-toxic up to the concentration tested, and are thus compatible with SHED.