A genetic code alteration generates a proteome of high diversity in the human pathogen <Emphasis Type="Italic">Candida albicans</Emphasis>

Background  

Genetic code alterations have been reported in mitochondrial, prokaryotic, and eukaryotic cytoplasmic translation systems, but their evolution and how organisms cope and survive such dramatic genetic events are not understood.     

The alternating current polarographic behavior and determination of lansoprazole and omeprazole in dosage forms and biological fluids

The alternating current (AC_t) polarographic behavior of lansoprazole (LNS) and omeprazole (OMP) was studied in Britton Robinson buffers (BRb) over the pH range 4.1–11.5. In BRb of pH 9.6 and 10.5, well-defined AC_t peaks were obtained for both LNS and OMP, respectively. The current–concentration plots were rectilinear over the ranges of 0.4–20 µg mL^− 1 and 0.2–10 µg mL^− 1 for LNS and OMP respectively. The minimum detection limits (S/N = 2) were 0.02 µg mL^− 1 (5.4 × 10^− 8 M) and 0.01 µg mL^− 1 (2.9 × 10^− 8 M) for LNS and OMP, respectively. The proposed method was successfully applied to the analysis of the two drugs in their commercial capsules. The average percent recoveries were favorably compared to those obtained by reference methods. Co-administered drugs such as naproxen and methotrexate did not interfere with the proposed method. The proposed method was further extended to the in-vitro determination of the lansoprazole in spiked plasma, the percentage recoveries was 98.47 ± 1.29 (n = 4). The pathway for the electrode reaction for both drugs involved reduction of the sulphonyl group into the corresponding thiol group at the Dropping Mercury Electrode. The advantages of the method were time saving and more sensitive than the other published voltammetric method. Yet The present study is the first report on the use of alterating current polarography (AC_t) in this respect.     

Neuropilin 1: function and therapeutic potential in cancer

Neuropilin 1 (NRP1) is a transmembrane glycoprotein that acts as a co-receptor for a number of extracellular ligands including class III/IV semaphorins, certain isoforms of vascular endothelial growth factor and transforming growth factor beta. An exact understanding of the role of NRP1 in the immune system has been obscured by the differences in NRP1 expression observed between mice and humans. In mice, NRP1 is selectively expressed on thymic-derived Tregs and greatly enhances immunosuppressive function. In humans, NRP1 is expressed on plasmacytoid dendritic cells (pDCs) where it aids in priming immune responses and on a subset of T regulatory cells (Tregs) isolated from secondary lymph nodes. Preliminary studies that show NRP1 expression on T cells confers enhanced immunosuppressive activity. However, the mechanism by which this activity is mediated remains unclear. NRP1 expression has also been identified on activated T cells and Tregs isolated from inflammatory microenvironments, suggesting NRP1 might represent a novel T cell activation marker. Of clinical interest, NRP1 may enhance Treg tumour infiltration and a decrease in NRP1+ Tregs correlates with successful chemotherapy, suggesting a specific role for NRP1 in cancer pathology. As a therapeutic target, NRP1 allows simultaneous targeting of NRP1-expressing tumour vasculature, NRP1+ Tregs and pDCs. With the development of anti-NRP1 monoclonal antibodies and cell-penetrating peptides, NRP1 represents a promising new target for cancer therapies. This paper reviews current knowledge on the role and function of NRP1 in Tregs and pDCs, both in physiological and cancer settings, as well as its potential as a therapeutic target in cancer.     

mda-7/IL-24: a unique member of the IL-10 gene family promoting cancer-targeted toxicity

Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) is a unique member of the IL-10 gene family that displays nearly ubiquitous cancer-specific toxicity, with no harmful effects toward normal cells or tissues. mda-7/IL-24 was cloned from human melanoma cells by differentiation induction subtraction hybridization (DISH) and promotes endoplasmic reticulum (ER) stress culminating in apoptosis or toxic autophagy in a broad-spectrum of human cancers, when assayed in cell culture, in vivo in human tumor xenograft mouse models and in a Phase I clinical trial in patients with advanced cancers. This therapeutically active cytokine also induces indirect antitumor activity through inhibition of angiogenesis, stimulation of an antitumor immune response, and sensitization of cancer cells to radiation-, chemotherapy- and antibody-induced killing.     

CHANGES IN CHEMICAL, SENSORY AND RHEOLOGICAL CHARACTERISTICS OF MANCHEGO CHEESES DURING RIPENING

Manchego cheese is a high-fat pressed ewe's-milk cheese made in Castilla-La Mancha (Spain) and produced by enzymatic coagulation. The minimum ripening time before marketing required by the Regulatory Board of the Manchego Cheese Appellation of Origin is 60 days.
This paper describes the physicochemical, proteolysis, sensory and texture characteristics of Manchego cheese, and the degree of homogeneity of cheeses made under the Manchego Appellation of Origin. The data gathered in this study indicate that sensory and instrumental analysis are useful tools for detecting changes in Manchego cheese during ripening. These changes were first detected by the instrumental analysis (2 months). The panelists detected differences after 4 months' ripening in all the factories. With physicochemical analysis, on the other hand, longer ripening times (6–8 months) are required before such changes become appreciated.     

COMPARISON OF TWO SIMPLE METHODS FOR THE MEASUREMENT OF DETECTION THRESHOLDS FOR BASIC, UMAMI AND METALLIC TASTES

Two simple methods were followed to determine detection thresholds for the taste of substances in aqueous solution. The methods applied were: a modification of the ascending method of limits and a method based on the use of scales. Detection thresholds were calculated for the four basic tastes (sweet, salty, acid, and bitterness), umami and metallic. Reference substances for each taste were sucrose, sodium chloride, citric acid, caffeine, monosodium glutamate and iron (II) sulfate heptahydrate and the results of the two methods were compared. We found that the threshold values calculated by method ASTM-679 was within the range of concentrations identified with the scales method.     

Isolation of High Density Lipoprotein Subclasses by Electrofiltration and Their Chemical Components

Abstract

The exact role of high density lipoprotein in atheroprotection is not well understood yet due to its complex nature; it comprises more than ten subclasses that vary in size, composition, and function. Isolation and characterization of these subclasses is an important step for further studies addressing their functions in health and disease. In this work, we present a novel method that is relatively simple and efficient for isolation of high density lipoprotein subclasses. The method depends on fractional filtration of the subclasses through a preformed gel membrane system under the effect of an electric field, where the stepwise isolation of the subclasses depends on differences in their rates of migration in polyacrylamide gel. Using this design, we were able to isolate seven high density lipoprotein subclasses with relative molecular masses of 42,000–50,000; 71,000; 103,000; 124,000; 150,000; 182,000; and 219,000. All the subclasses contained apolipoprotein A-I, phosphatidylcholine, sphingomyelin, free cholesterol, esterified cholesterol, and triacylglycerols. Some fractions of some samples contained the apolipoproteins A-II, C-I, C-II, C-III, and E. A subclass of molecular mass of 106,000 was identified and isolated from a healthy young subject that contained albumin and apoA-I with some free and esterified cholesterol, but with no triacylglycerols. This electrofiltration technique offers a novel tool for isolating pure native high density lipoprotein subclasses in a concentrated form that can be used directly for detailed studies of their physicochemical and physiological properties.     

Simple and sensitive spectrofluorimetric method for the determination of pregabalin in capsules through derivatization with fluorescamine

A new, simple and sensitive spectrofluorimetric method has been developed for the determination of pregabalin (PG) in capsules. The method is based on the reaction between pregabalin and fluorescamine in borate buffer solution of pH 10 to give a highly fluorescent derivative that is measured at 487 nm after excitation at 390 nm. The different experimental parameters affecting the development and stability of the reaction product were carefully studied and optimized. The fluorescence intensity concentration plot was rectilinear over the range of 0.01–0.3 µg mL^?1 with a lower detection limit of 0.0017 µg mL^?1 and limit of quantitation of 0.005 µg mL^?1. The developed method was successfully applied to the analysis of the drug in its commercial capsules. The mean percentage recovery of PG in its capsule was 99.93±1.24 (n = 3). Statistical comparison of the results with those of the comparison method revealed good agreement and proved that there was no significant difference in the accuracy and precision of the two methods. A proposed reaction pathway was postulated. Copyright © 2010 John Wiley & Sons, Ltd.