Chemical Biology

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.

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.

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 ...

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.