A doubly inducible system for RNA interference and rapid RNAi plasmid construction in Trypanosoma brucei.

The most rapid method for the generation of conditional mutants in Trypanosoma brucei is the use of RNA interference. A single copy of the target sequence is cloned between two opposing T7 promoters bearing tet operators, and the resulting plasmid is integrated into the genome of cells expressing both the tet repressor and T7 RNA polymerase. Upon addition of tetracycline, double-stranded RNA is synthesised from the two T7 promoters.

Discovery of inhibitors of human adipocyte fatty acid-binding protein, a potential type 2 diabetes target.

Low micromolar human A-FABP inhibitors were found by utilizing a fluorescence polarization assay, X-ray crystallography and modeling. The carbazole- and indole-based inhibitors displayed approximately 10-fold preferences over human H-FABP and E-FABP, and are highly selective against I-FABP. This communication describes the SAR for drug-like synthetic inhibitors of human A-FABP.

A high-performance cathode for the next generation of solid-oxide fuel cells.

Fuel cells directly and efficiently convert chemical energy to electrical energy. Of the various fuel cell types, solid-oxide fuel cells (SOFCs) combine the benefits of environmentally benign power generation with fuel flexibility. However, the necessity for high operating temperatures (800-1,000 degrees C) has resulted in high costs and materials compatibility challenges.

Patterns and correlates of sexual initiation, sexual risk behaviors, and condom use among secondary school students in Ethiopia.

This study explored the patterns and socio-demographic correlates of sexual initiation, subsequent risk behaviors, and condom use among secondary school youth across Ethiopia. A total of 1,102 students were selected on convenience basis from five urban schools (in Baher Dar, Dessie, Awassa, Jimma, and Dire Dawa) and surveyed about their sexual and preventive behaviors using an extensive questionnaire. Data were analyzed using bivariate and multivariate statistical procedures.

Validation of Trypanosoma brucei trypanothione synthetase as drug target.

In trypanosomes, the parasite-specific thiol trypanothione [T(SH)2] fulfills various functions, the best established being detoxification of H2O2 and organic hydroperoxides and ribonucleotide reduction. Recently, a trypanothione synthetase (Tb-TryS) gene from Trypanosoma brucei was isolated and the heterologously expressed Tb-TryS catalyzed the entire synthesis of T(SH)2 from glutathione (GSH) and spermidine in vitro. To confirm the in situ function of the complex Tb-TryS activities and to evaluate the importance of T(SH)2 metabolism in T.

High-performance solid Acid fuel cells through humidity stabilization.

Although they hold the promise of clean energy, state-of-the-art fuel cells based on polymer electrolyte membrane fuel cells are inoperable above 100 degrees C, require cumbersome humidification systems, and suffer from fuel permeation. These difficulties all arise from the hydrated nature of the electrolyte. In contrast, "solid acids" exhibit anhydrous proton transport and high-temperature stability.

A role for the exosome in the in vivo degradation of unstable mRNAs.

In mammals, the mRNAs encoding many proteins involved in inflammation bear destabilizing AU-rich elements (AREs) in the 3'-untranslated region. The exosome, a complex of 3' --> 5' exonucleases, is rate limiting in the destruction of such mRNAs in a mammalian in vitro system, but a role in vivo has not been demonstrated. The phenomenon of ARE-mediated degradation also occurs in the protist parasite Trypanosoma brucei.

Solid acids as fuel cell electrolytes.

Fuel cells are attractive alternatives to combustion engines for electrical power generation because of their very high efficiencies and low pollution levels. Polymer electrolyte membrane fuel cells are generally considered to be the most viable approach for mobile applications. However, these membranes require humid operating conditions, which limit the temperature of operation to less than 100 degrees C; they are also permeable to methanol and hydrogen, which lowers fuel efficiency.

X-ray diffraction study of K3NdSi7O17: a new framework silicate with a linear Si-O-Si bond.

Hydrothermal investigations in the high-silica region of the K(2)O-Nd(2)O(3)-SiO(2) system, carried out in a search for novel fast-ion conductors (FICs), yielded the new compound tripotassium neodymium heptasilicate, K(3)NdSi(7)O(17). Single-crystal X-ray methods revealed that K(3)NdSi(7)O(17) crystallizes in space group P3, has lattice constants a = 16.131 (2) and c = 7.

Structure and thermal behavior of the new superprotonic conductor Cs2(HSO4)(H2PO4).

Ongoing studies of the CsHSO(4)-CsH(2)PO(4) system, aimed at developing novel proton conducting solids, resulted in the new compound Cs(2)(HSO(4))(H(2)PO(4)) (dicesium hydrogensulfate dihydrogenphosphate). Single-crystal X-ray diffraction (performed at room temperature) revealed Cs(2)(HSO(4))(H(2)PO(4)) to crystallize in space group P2(1)/n with lattice parameters a = 7.856 (8), b = 7.

Single-crystal neutron diffraction study of beta-Cs3(HSO4)2.

The structure of beta-Cs(3)(HSO(4))(2)[H(2-x)(S(x)P(1-x))O(4)] has been examined by single-crystal neutron diffraction at 15 K. The compound crystallizes in space group C2/c and contains four formula units in the unit cell, with lattice parameters a = 19.769 (9), b = 7.

Structure and thermal behavior of the new superprotonic conductor Cs2(HSO4)(H2PO4). Erratum.

Table 2 in the paper by Chisholm & Haile [(1999), Acta Cryst. B55, 937-946] was printed incorrectly. The correct version is presented, including H-atom coordinates.

Structure, phase transitions and ionic conductivity of K3NdSi6O15 x xH2O. II. Structure of beta-K3NdSi6O15.

Hydrothermally grown crystals of beta-K3NdSi6O15, potassium neodymium silicate, have been studied by single-crystal X-ray methods. Under appropriate conditions, the compound crystallizes in space group Bb2(1)m and has lattice constants a = 14.370 (2), b = 15.

Structure, phase transitions and ionic conductivity of K3NdSi6O15 x xH2O. I. Alpha-K3NdSi6O15 x 2H2O and its polymorphs.

Hydrothermally grown crystals of alpha-K3NdSi6O15 x 2H2O, potassium neodymium silicate, have been studied by single-crystal X-ray methods. The compound crystallizes in space group Pbam, contains four formula units per unit cell and has lattice constants a = 16.008 (2), b = 15.

Suppression of immediate and late responses to antigen by a non-anaphylactogenic anti-IgE antibody in a murine model of asthma.

Eosinophils are recruited to the airways during allergic reactions, but animal models have shown that their mere presence is not sufficient for the development of bronchopulmonary hyperreactivity. Other factors, such as immunoglobulin (Ig)E, seem to be required. Using mice selected for the production of large amounts of IgE, the effects of antibody neutralization of IgE on antigen-induced lung recruitment of eosinophils and induction of bronchopulmonary hyperreactivity and of other indicators of inflammation were studied.

Mucous-cell metaplasia and inflammatory-cell recruitment are dissociated in allergic mice after antibody- and drug-dependent cell depletion in a murine model of asthma.

Inflammatory-cell infiltration and epithelial modifications are prominent lesions of the bronchial mucosa in asthma and in experimental allergic bronchopulmonary inflammation. However, the recruitment of inflammatory cells and their relationship to the epithelial modifications and to functional alterations such as bronchopulmonary hyperreactivity (BHR) are less known. We studied the mechanisms of antigen-dependent inflammatory-cell recruitment to the lungs and the associated lesions and their relationship using drug- and antibody-dependent cell-depletion procedures.

Requirement for gammadelta T cells in allergic airway inflammation.

The factors that contribute to allergic asthma are unclear but the resulting condition is considered a consequence of a type-2 T helper (TH2) cell response. In a model of pulmonary allergic inflammation, mice that lacked gammadelta T cells had decreases in specific immunoglobulin E (IgE) and IgG1 and pulmonary interleukin-5 (IL-5) release as well as in eosinophil and T cell infiltration compared with wild-type mice. These responses were restored by administration of IL-4 to gammadelta T cell-deficient mice during the primary immunization.

Inhibition of airways inflammation by dexamethasone is followed by reduced bronchial hyperreactivity in BP2 mice.

Background: Infiltration of inflammatory cells in the airways is a constant characteristic of asthma and is considered to result in bronchial hyperreactivity (BHR). We have recently developed a model of BHR using a selection of mice, named BP2, which display eosinophil-dependent BHR following antigen challenges. An anti-IL-5 antibody suppressed antigen-induced eosinophil recruitment to the airways and BHR in BP2 mice.

Fas-mediated apoptosis in cultured human eosinophils.

Previous studies have shown that cytokine-dependent eosinophils undergo apoptosis, yet the mechanisms governing this phenomenon remain obscure. Fas antigen is a transmembrane glycoprotein belonging to the tumor necrosis factor receptor family. Cross-linking of Fas antigen in numerous cell types leads to apoptosis.

Eosinophil recruitment into the respiratory epithelium following antigenic challenge in hyper-IgE mice is accompanied by interleukin 5-dependent bronchial hyperresponsiveness.

A murine model for antigen-induced bronchial hyperreactivity (BHR) and airway eosinophilia, two hallmarks of asthma, was developed using ovalbumin-immunized mice, which produce large amounts of IgE (named BP2, "Bons Producteurs 2," for High Line of Selection 2). A single intranasal ovalbumin challenge failed to modify the bronchial responses, despite the intense eosinophil recruitment into the bronchoalveolar lavage fluid and airways. When mice were challenged twice a day for 2 days or once a day for 10 days, BHR in response to i.

Interleukin-10 inhibits antigen-induced cellular recruitment into the airways of sensitized mice.

This report examines the effect of recombinant murine (rm) IL-10 on antigen-induced cellular recruitment into the airways of sensitized Balb/c mice. The intranasal instillation of 10 micrograms ovalbumin induced an early (6-24 h) increase in the number of neutrophils, and a late rise (24-96 h) in that of eosinophils in the bronchoalveolar lavage (BAL) fluid and bronchial tissue. A single intranasal instillation of 0.