With the aim of developing a new enzyme-linked immunosorbent assay test to detect autoantibodies in the sera of rheumatoid arthritis patients with a high sensitivity and specificity using synthetic citrullinated peptides of fibrin (which is abundant in rheumatoid synovium) as antigenic substract, peptides belonging to α- and β-fibrin chains were selected by computer-aided prediction of antigenicity and epitope mapping and synthesized in solid phase. We analysed by enzyme-linked immunosorbent assay 133 sera from patients with well-characterized rheumatic diseases, including 67 patients with rheumatoid arthritis. The results of the immunoassays reported highlight the usefulness of fibrin-related peptides in rheumatoid arthritis diagnosis and, especially, the ability and specificity of the [Cit621,627,630]α-fibrin(617–631) (αfib617) peptide sequence to recognize the autoantibodies that are present in rheumatoid arthritis patients.

Recent achievements have been made in the metabolic engineering of plant secondary metabolism. Various pathways have been altered using genes encoding biosynthetic enzymes or genes encoding regulatory proteins. In addition, antisense genes have been used to block competitive pathways, thereby increasing the flux towards the desired secondary metabolites.

BACKGROUND:
In spite of its indusrial usefulness and varied daily uses, lead (Pb) pollution is a widespread ecological problem that faces the humans in the 21th century. Pb was found to produces a wide range of toxic effects including neurotoxicity especially to the developing and young offspring. Recently, the utilization of herbal plants has received a significant attention where there has been rising awareness in their therapeutic use; among these is the garlic.
AIM OF THE WORK:
In light of the above, the current study is designed experimentally in female pregnant rats in order to investigate the beneficial role of garlic extract in the protection from the maternal and fetal cerebellar damage that produced by administration of different doses of Pb during pregnancy.
MATERIALS AND METHODS:
Positively pregnant female rats were divided into five groups; one control group, two Pb-treated groups (exposed to 160 and 320 mg/kg b.wt. of Pb, respectively) and two groups treated with both Pb and garlic (exposed to Pb as previous groups together with 250 mg/ kg b.wt. /day of garlic extract). Treatments started from day 1 till day 20 of pregnancy, where the mother rats of different experimental groups were sacrified to obtain the fetuses. Pb level in the maternal nd fetal blood and cerebellum was estimated by spectrophotometry. Specimens of the cerebellum of different mother and fetal groups were processed to histological and immunohistochemical staining for microscopic examination.
RESULTS:
The results showed that administration of Pb to pregnant rats resulted in a dose-dependent toxicity for both mothers and fetuses in the form of decrease of maternal weight gain, placental and fetal weights, brain weight and diminished fetal growth parameters, which were prominent in rat's group treated with larger dose of Pb. In Pb-treated rats, Pb level in blood and cerebellum was high when compared to the control. The histopathological examination of the cerebellum of treated dams and fetuses showed marked alterations mainly in the form of Purkinje cell degeneration and lack of deveopmet of fetal cerebellum. Co-treatment of garlic extract along with Pb resulted in a significant decrease in Pb levels as compared with those treated with Pb alone with improvement of the histopathological changes.
CONCLUSIONS:
This study was useful in evaluating the hazardous effects of uncontrolled use of Pb in general and in assessing the developmental and neurotoxicity of fetuses due to exposure during pregnancy in particular. Co-administration of garlic has beneficial effects in amelioration of Pb-induced neurotoxicity and reversing the histopathological changes of the cerebellum of mother rats and fetuses.
KEYWORDS:
garlic; glial fibrillary acidic protein; lead; purkinje cells

A study of the methylation of N-nosyl-α-amino acids and derivatives with trimethylsilyldiazomethane is here reported. Trimethylsilyldiazomethane allows the chemo-specific methylation of the carboxyl function of N-nosyl-α-amino acids in high yields and purity. This method provides a practical route to N-methyl-α-amino acids avoiding the use of the more toxic and explosive diazomethane. This simple and safe methylation methodology of α-amino acids and derivatives is not limited to organic synthesis and involves the use of a commercially available reagent as well.

Platinum-based heterogeneous catalysts are critical to many important commercial chemical processes, but their efficiency is extremely low on a per metal atom basis, because only the surface active-site atoms are used. Catalysts with single-atom dispersions are thus highly desirable to maximize atom efficiency, but making them is challenging. Here we report the synthesis of a single-atom catalyst that consists of only isolated single Pt atoms anchored to the surfaces of iron oxide nanocrystallites. This single-atom catalyst has extremely high atom efficiency and shows excellent stability and high activity for both CO oxidation and preferential oxidation of CO in H2. Density functional theory calculations show that the high catalytic activity correlates with the partially vacant 5d orbitals of the positively charged, high-valent Pt atoms, which help to reduce both the CO adsorption energy and the activation barriers for CO oxidation.

AUGUST 28, 2013

Washington — An attack on Syria may indeed spread the war -- and risks escalation and backlash -- but larger interests are at stake. Like it or not, the US is the world's sheriff in these matters.

A deeply flawed analysis recently published in the Guardian exposes the weakest of all arguments against the West taking action, that being because, "chemical weapons are far from being the greatest threat to Syria's people."

The point is that WMD use is a threat to ALL humanity. (download to read more)

Photo Credits:  Save the Children of Syria. TAHIR SQUARE, Egypt — While Egypt's Revolution has, at least for now, moved into a battle for ballots, the legacy of Arab Spring remains bloodied by bullets and bombs in Syria. The destruction, danger, and death in Syria is not new but groups in Egypt tried to raise awareness during the 2012 Egyptian Presidential campaign, both as a direct call to action and as warning of what might happen should civil war break out in Egypt. 25 May, 2012. ©LMG. Photo by K. Lee Lerner. All rights reserved.

A wide range of methods exist for the on-plate detection of lipids resolved by thin layer chromatography. Fluorescence generally offers improvements in sensitivity over methods that use colorimetric or simple densitometric detection. In this paper, we report that a classic cupric sulfate charring protocol produces a fluorescent signal that sensitively and quantitatively detects a wide range of phospholipids, neutral lipids, and sterols after automated, multi-development high performance thin layer chromatography. The measured lower limits of detection and quantification, respectively, were, on average, 80 and 210 pmol for phospholipids and 43 fmol and 8.7 pmol for sterols. The simple, inexpensive, and highly sensitive approach described here was used to quantitatively analyze the lipid and sterol composition of sea urchin cortical vesicles, a stage-specific model system used to study the mechanism of regulated membrane fusion.

Hybrid materials based on polyvinylpyrrolidone (PVP) with silver nanoparticles (AgNps) were synthesized applying two different strategies based on thermal or chemical reduction of silver ions to silver nanoparticles using PVP as a stabilizer. The formation of spherical silver nanoparticles with diameter ranging from 9 to 16 nm was confirmed by TEM analysis. UV-vis and FTIR spectroscopy were also applied to confirm the successful formation of AgNps. The antibacterial activity of the synthesized AgNPs/PVP against etalon strains of three different groups of bacteria-Staphylococcus aureus (S. aureus; grampositive bacteria), Escherichia coli (E. coli; gram-negative bacteria), Pseudomonas aeruginosa (P. aeruginosa; nonferment gram-negative bacteria), as well as against spores of Bacillus subtilis (B. subtilis) was studied. AgNps/PVP were tested for the presence of fungicidal activity against different yeasts and mold such as Candida albicans, Candida krusei, Candida tropicalis, Candida glabrata, and Aspergillus brasiliensis. The hybrid materials showed a strong antimicrobial effect against the tested bacterial and fungal strains and therefore have potential applications in biotechnology and biomedical science.

The effects of the linker arm rigidity and size on melanocortin receptor selectivity were explored in a series of compounds using cyclic lactam alpha-melanocyte-stimulating hormone template. A variety of dicarboxylic acid linkers introduced between the alpha-amino group of His(6) and the epsilon-amino group of Lys(10) lead to high-affinity, selective human melanocortin receptor-1 and -5 (hMC1R and hMC5R) antagonists. The incorporation of hydrophilic functions into the linker arm was found to be unfavorable for both binding potency and receptor selectivity. Analogs 8 and 9 containing highly conformationally constrained hydrophobic linkers (m- and p-phthalic acids) were found to be selective nanomolar range hMC1R antagonists (IC(50) = 7 and 4 nm, respectively), whereas the employment of a small conformationally constrained linker (maleic acid) resulted in a high-affinity (IC(50) = 19 nm) and selective hMC5R antagonist (analog 12). These newly developed melanotropins will serve as critical biochemical tools for elucidating the full spectrum of functions performed by the physiologically important melanocortin-1 and -5 receptors.

In this work, we study the formulation and production of natural fermentation BREAD, also said "earth", which is based on the fact that this process can play a clearly defined role in the direction of improving the promoters, the structure of the bread to the stabilization or increase in the levels of different bioactive compounds, slow starch bioavailability (low index glucemico products) is to improve bioavailability minerals highly consumed in this product. Panels were produced from the fermentation of earth" using Kluyveromyces marxianus, Dekkera and Brettanomyces bruxelenses Lactobacillus plantarum starting major crops. The seven samples from the mixture of design Simplex at 0076\azA\\a A|zSAQ ‘azxsa ‘1QASZ\Q ‘1QASWQ’ 1SDF’1111111cvx c determines the specific volume of bread and ph, decrease and viable cells during the process of fermentation "mass" and noted that the bread prepared Lactobacillus plantarum has the lowest specific volume, even if the combination of K. marxianus and L. plantarum had positive influence, which leads to great specific volume. In the course of the fermentation process "earth" to record a reduction in ph and an increase in the fall. Both the sensory analysis, are a high acceptability and the production of bread with the mixture of D. Brettanomyces bruxelenses and K. Marxianus is the combination of the three micro-organisms. The results indicate that the types of culture exert a significant influence of the quality of the bread the parameters on the tool. As always, other studies should examine other variables of fermentation process "earth" to be completed, in order to better understand the technical product.
Keywords: Manufacturing, breads, Production, Baking .

This research was funded by, and implemented within, a UK national research organisation, while the author was the KE and Impact Evaluation Manager responsible for assessing impact on a £15m UK government-funded research programme.

This work was also submitted as the authors MBA dissertation which was accepted and awarded in 2009.

ABSTRACT: A methodology and methods ‘toolbox’ is proposed for conducting impact research and assessment from within research programmes. The emphasis is upon how to clarify and assess the wider impacts from the early stages onwards.

The approach explicitly acknowledges, and attempts to address, the known issues and challenges of impact assessment while drawing upon the resources and opportunities available to research managers and researchers within such programmes.

The study has two triangulating foundations. Firstly, it examines the academic literature to help identify and design the pilot methodology and methods. Secondly it trials these in a real programme to both test and improve them.

The study was conducted over one year within one leading UK research organisation, where two research programmes (and around 60 research projects of £15m total value) were being assessed for their impacts. The study draws upon actual impact management experience and reflection, prospective (ex ante) and retrospective (ex post) assessments, participatory contributions from leading researchers undergoing assessment, and consultation with external users. The findings of this study outline the pilot and its first iteration. Recommendations are made for improvement to the methodology and methods.

A subsequent follow-on bid to UK government incorporating the impacts identified from implementing this methodology, successfully led to a further £15m of government funding.

It is expected the pilot methodology and methods will be applicable to other organisations, conducting and funding such research programmes, required to research and assess the wider research impacts.

Although primary focus of implemetation trials was upon research in physical sciences, technology, high-tech engineering, computing/IT, and environment, the wider literature study, the methodology design and justification, the methods proposed and used, and the resulting general recommendations and lessons are expected to apply more broadly to many other research areas, where the impact is to be found more widely in the society, economy, government or public sector or within organizations, policies, professions or the public.

Interest in this work is expected from research programme managers, impact managers and assessors, management consultants advising in this area, and government funding managers, all seeking to embed a developing approach to understand, capture, and enhance wider impact.

Abbreviations 2-DE two-dimensional electrophoresis AP atmospheric pressure CAI codon adaptation index CE capillary electrophoresis CID collision-induced dissociation ESI electrospray ionization FT-ICR Fourier transform ion cyclotron resonance ICAT TM isotope-coded affinity tag IMAC immobilized metal affinity chromatography MALDI matrix-assisted laser desorption/ionization MS/MS tandem MS MudPUT multidimensional protein identification technology PTM post-translational modification RF radiofrequency SELDI surface-enhanced laser desorption/ionisation TAP tandem affinity purification TOF time-of-flight

A series of 18 novel 2-hydrazolyl-4-thiazolidinones-5-carboxylic acids, amides and 5,6-a,b-unsaturated esters were synthesized, and their in vitro activity on cruzipain and T. cruzi epimastigotes was determined. Some agents show activity at 37 lM concentration in the enzyme assay. Computational tools and docking were used to correlate the biological response with the physicochemical parameters of the compounds and their cruzipain inhibitory effects.

Twenty new quinoxalines bearing azetidinone and thiazolidinone groups were synthesized by cyclocondensation of Schiff bases of quinoxaline-2, 3-dione and were characterized with several analytical tools. They were tested against Mycobacterium tuberculosis H37Rv at a concentration of 10 lg ⁄ mL by Microplate Alamar Blue Assay method. Quinoxaline derivatives with 2-chloro, dimethylamino and nitro substitutions exhibited in vitro activity, comparable to that of the drug, isoniazid. Three-dimensional quantitative structure-activity relationship studies indicated that electrostatic and steric field descriptors could explain the observed activity. The developed model fits the data well and has good predictive capability (r 2 = 0.81, q 2 = 0.71, F = 27.06, r 2 _pred = 0.84, r 2 m = 0.84, r 2 BS = 0.80). Electronegative groups play an important role in the antitubercular activity.

Recent studies on microbial cytochrome P450 enzymes have covered several new areas. Advances have been made in structure–function analysis and new non-enzymatic/electrochemical systems for the replacement of NAD (P) H in biocatalysis have been ...

Nine biologically significant organotin(IV) esters of 3,4-Methylenedioxyphenylpropenoic acid (L) were synthesized with the general formulae [R 2 SnL 2 ], where R includes Me(1), Et(3), But(4), Oct(5), Ph(8), and [R 3 SnL], in which R is Me(2), Cy(6), Ph(7), and But(9). The acid and its compounds were characterized by basic analytical techniques comprising elemental analysis, FTIR and mass spectrometry in solid state and by Multinuclear ( 1 H, 13 C and 119 Sn) NMR in solution form, which provides some important information about the different coordination behaviors of metal in both solid and solution. Methylenedioxy moiety in these compounds enhances the biological activity of these compounds. These compounds were screened for a range of biological activities. Antibacterial activities were determined against six pathogenic bacterial strains, three gram-positive and three gram-negative, the activities were measured in terms of inhibition zones (mm). Results demonstrate that diorganotin derivatives are more active than triorganotin derivatives and ligand acid. Antifungal activity was determined against six pathogenic fungal strains, cytotoxicity by the brine shrimp lethality assay, and antitumor activity by crown gall tumor inhibition (potato disc) assay. Results for antifungal activity, cytotoxicity, and antitumor activity of these compounds demonstrate that triorganotin derivatives are more active than diorganotin derivatives and ligand. Finally, the results were compared with similar reports in the literature.

CITATIONS 14 READS 59 4 authors: Some of the authors of this publication are also working on these related projects: I am working on biosensors View project 1) The impact of modification and mutagenesis on structure and function of lens crystallins. 2) Anticancer activity assessment of novel platinum-based complexes. 3) Development of novel antidiabetic compounds with inhibitory action against alpha-amylase and alpha-glucosidase enzymes.

Graphite oxide is one of the main precursors of graphene-based materials, which are highly promising for various technological applications because of their unusual electronic properties. Although epoxy and hydroxyl groups are widely accepted as its main functionalities, the complete structure of graphite oxide has remained elusive. By interpreting spectroscopic data in the context of the major functional groups believed to be present in graphite oxide, we now show evidence for the presence of five-and six-membered-ring lactols. On the basis of this chemical composition, we devised a complete reduction process through chemical conversion by sodium borohydride and sulfuric acid treatment, followed by thermal annealing. Only small amounts of impurities are present in the final product (less than 0.5 wt% of sulfur and nitrogen, compared with about 3 wt% with other chemical reductions). This method is particularly effective in the restoration of the p-conjugated structure, and leads to highly soluble and conductive graphene materials.

Circularly polarized light (CPL) emitted from star-forming regions is an attractive candidate as a cause of single chirality in nature. It has remained difficult, however, to translate the relatively small chemical effects observed on irradiation of molecular systems with CPL into high enantiomeric excesses. Here we demonstrate that irradiation of a racemic amino acid derivative with CPL leads to a small amount of chiral induction that can be amplified readily to give an enantiopure solid phase. A racemate composed of equal amounts of left-and right-handed crystals in contact with the irradiated solution is converted completely into crystals of single-handedness through abrasive grinding when racemization is effected in the solution. The rotation sense of the CPL fully determines the handedness of the final solid state. These findings illustrate the potential effectiveness of CPL in the control of molecular asymmetry, which is relevant for the origin of the single chirality inherent to many biological molecules.

N-Myristoyl transferase is an essential enzyme for fungal growth and survival. The continuous interest in the development of new antifungal agents prompted recent interest in developing new potent inhibitors of fungal N-myristoyl transferase. In this context, we combined pharmacophore and QSAR modeling to explore the structural requirements for potent N-myristoyl transferase inhibitors employing 55 known N-myristoyl transferase ligands. Four binding pharmacophore models emerged in the optimal QSAR equations (r 2 44 = 0.81-0.83, F-statistic = 47.89-58.83, r 2 LOO = 0.77-0.80, r 2 PRESS against 11 external test inhibitors = 0.61-0.71). The successful pharmacophores were complemented with exclusion spheres to optimize their receiver operating characteristic curve profiles. The QSAR equations and their associated pharmacophore models were validated by the identification and experimental evaluation of new promising antifungal leads retrieved from the NCI database and our in-house-built database of established drugs and agrochemicals.

Novispirin G 10 is an a-helical antimicrobial peptide designed in an effort to develop alternative treatments against multidrug-resistant micro-organisms. To further optimize the antimicrobial activity, 58 novispirin analogs were constructed and used to establish a quantitative structure-activity relationship model. A statistically significant model (r 2 ¼ 0.73, q 2 ¼ 0.61) was obtained using a set of 69 selected molecular descriptors. Among these, Vol-Surf and charged partial surface area descriptors played a dominant role. Analysis of the model indicated that hydrophobicity, amphipathicity and charge were the most important features influencing activity for this set of peptides. Furthermore, the ability of the quantitative structure-activity relationship model to predict bioactivity was evaluated by analyzing a set of 400 novispirin analogs designed by molecular modeling. Out of these 400, 16 new novispirins with a higher predicted antimicrobial activity were tested in the suicide expression system, and about three out of four appeared more potent than the parent novispirin G 10 . Combination of VolSurf and charged partial surface area descriptors seems relevant to depict the interaction between novispirin and its target(s), presumably the microbial cell membrane. The presented findings show that modeling and quantitative structure-activity relationship methods can be useful in the construction of and/or optimization of the bioactivity of antimicrobial peptides for further development as effective antibiotic therapeutics.

Infectious diseases are the leading causes of death worldwide. Hence, there is a need to develop new antimicrobial agents. Traditional method of drug discovery is time consuming and yields a few drug targets with little intracellular information for guiding target selection. Thus, focus in drug development has been shifted to computational comparative genomics for identifying novel drug targets. Leptospirosis is a worldwide zoonosis of global concern caused by Leptospira interrogans. Availability of L. interrogans serovars and human genome sequences facilitated to search for novel drug targets using bioinformatics tools. The genome sequence of L. interrogans serovar Copenhageni has 5,124 genes while that of serovar Lai has 4,727 genes. Through subtractive genomic approach 218 genes in serovar Copenhageni and 158 genes in serovar Lai have been identified as putative drug targets. Comparative genomic approach had revealed that 88 drug targets were common to both the serovars. Pathway analysis using the Kyoto Encyclopaedia of Genes and Genomes revealed that 66 targets are enzymes and 22 are non-enzymes. Sixty two common drug targets were predicted to be localized in cytoplasm and 16 were surface proteins. The identified potential drug targets form a platform for further investigation in discovery of novel therapeutic compounds against Leptospira.

Modulation of the immune system can be addressed through a variety of specific and non-specific approaches. Many agents of synthetic and natural origin have stimulatory, suppressive or regulatory activity. There is growing evidence that drugs or biological agents capable of modulating single pathways or targets are of limited value as immune-related therapies. Systems biology approaches are now gaining more interest compared with monovalent approaches, which can be of limited benefits with complications. This has stimulated interest in the use of ‘cocktails’ of immunodrugs to restore immunostasis. Botanicals are chemically complex and diverse and could therefore provide appropriate combinations of synergistic moieties useful in drug discovery. Here, the importance of traditional medicine in natural product drug discovery related to immunodrugs is reviewed.

Expressed protein ligation (EPL) and bioconjugation based on the maleimide group (MIC-conjugation) provide powerful tools for protein modification. In the light of the importance of site-selectively modified proteins for the study of protein function, a flexible method for the introduction of tags and reporter groups into the C-terminus of proteins employing EPL and MIC-conjugation was developed. We describe the solid-phase synthesis of a generic building block, equipped with fluorescence markers or different functional groups. This generic building block allows for a flexible incorporation of different tags into proteins and was used for the introduction of fluorescence markers into the C-terminus of Rab and Ras GTPases by EPL or MIC-conjugation techniques. In addition, a building block appropriately modified for the incorporation of an azide into proteins was synthesized. Azide-functionalized Ras protein was immobilized on a phosphane-modified surface by means of Staudinger ligation providing a highly chemoselective ligation method for the immobilization of proteins.