Functional Analysis of the Cathepsin-Like Cysteine Protease Genes in Adult Brugia malayi Using RNA Interference

Filarial nematodes are an important group of human pathogens, causing lymphatic filariasis and onchocerciasis, and infecting around 150 million people throughout the tropics with more than 1.5 billion at risk of infection. Control of filariasis currently relies on mass drug administration (MDA) programs using drugs which principally target the microfilarial life-cycle stage. These control programs are facing major challenges, including the absence of a drug with macrofilaricidal or permanent sterilizing activity, and the possibility of the development of drug-resistance against the drugs available. Cysteine proteases are essential enzymes which play important roles in a wide range of cellular processes, and the cathepsin-like cysteine proteases have been identified as potential targets for drug or vaccine development in many parasites. Here we have studied the function of several of the cathepsin-like enzymes in the filarial nematode, B. malayi, and demonstrate that these cysteine proteases are involved in the development of embryos, show similar functions to their counterparts in C. elegans, and therefore, provide an important target for future drug development targeted to eliminate filariasis

INTRAMOLECULAR N-H...O=C HYDROGEN-BONDING ASSISTED BY RESONANCE - INTERCORRELATION BETWEEN STRUCTURAL AND SPECTROSCOPIC DATA FOR 6 BETA-DIKETO-ARYLHYDRAZONES DERIVED FROM BENZOYLACETONE OR ACETYLACETONE

Crystal structure determinations of six beta-diketo-arylhydrazones have been accomplished with the aim of a detailed investigation of the nature of the intramolecular hydrogen bond formed by the HN-N=C-C=O fragment in these compounds. The N...O hydrogen bond distances are found to be correlated with the values of the spectroscopic parameters, i.e. IR nu(NH) stretching frequencies, H-1 NMR chemical shifts, lambda(max) of the UV absorption of the charge-transfer (CT) band from the hydrazone to the carbonyl group, and the Hammett constants, sigma(X), of the substituent X on the N-phenyl group. Experiments show that the hydrogen bond is characterized by the following interrelated features: ((i) very short N...O distances (2.551-2.600 angstrom); (ii) strong delocalization in the keto-hydrazone fragment; (iii) lowering of the nu(NH) frequencies (3002-3117 cm-1); (iv) H-1 NMR downfield shift of the proton resonance (14.53-14.93 ppm); and (v) UV lambda(max)(CT) in the range 370-406 nm. These findings are interpreted in terms of the RAHB (Resonance-Assisted Hydrogen Bonding) model [Gilli G., Bellucci F., Ferretti V., Bertolasi V., J. Am. Chem. Soc., 1989, 111, 1023]. We show that the magnitude of the strong hydrogen bond is essentially determined by the degree of pi-delocalization within the keto-hydrazone heteroconjugated system and modulated by all others factors that can affect the degree of pi-conjugation, including inductive effects and non-bonded intermolecular interactions

Structural systematics of the anhydrous 1:1 proton-transfer compounds of 3,5-dinitrosalicylic acid with aniline and monosubstituted anilines

The crystal structures of the proton-transfer compounds of 3,5-dinitrosalicylic acid (DNSA) with a series of aniline-type Lewis bases [aniline, 2-hydroxyaniline, 2-methoxyaniline, 3-methoxyaniline, 4-fluoroaniline, 4-chloroaniline and 2-aminoaniline] have been determined and their hydrogen-bonding systems analysed. All are anhydrous 1:1 salts: [(C6H8N)+(C7H3N2O7)-], (1), [(C6H8NO)+(C7H3N2O7)-], (2), [(C7H10NO)+(C7H3N2O7)-], (3), [(C7H10NO)+(C7H3N2O7)-], (4), [(C6H7FN)+(C7H3N2O7)-], (5), [(C6H7ClN)+(C7H3N2O7)-], (6), and [(C6H9N2)+(C7H3N2O7)-], (7) respectively. Crystals of 1 and 6 are triclinic, space group P-1 while the remainder are monoclinic with space group either P21/n (2, 4, 5 and 7) or P21 (3). Unit cell dimensions and contents are: for 1, a = 7.2027(17), b = 7.5699(17), c = 12.9615(16) Å, α = 84.464(14), β = 86.387(15), γ = 75.580(14)o, Z = 2; for 2, a = 7.407(3), b = 6.987(3), c = 27.653(11) Å, β = 94.906(7)o, Z = 4; for 3, a = 8.2816(18), b = 23.151(6), c = 3.9338(10), β = 95.255(19)o, Z = 2; for 4, a = 11.209(2), b = 8.7858(19), c = 15.171(3) Å, β = 93.717(4)o, Z = 4; for 5, a = 26.377(3), b = 10.1602(12), c = 5.1384(10) Å, β = 91.996(13)o, Z = 4; for 6, a = 11.217(3), b = 14.156(5), c = 4.860(3) Å, α = 99.10(4), β = 96.99(4), γ = 76.35(2)o, Z = 2; for 7, a = 12.830(4), b = 8.145(3), c = 14.302(4) Å, β = 102.631(6)o, Z = 4. In all compounds at least one primary linear intermolecular N+-H…O(carboxyl) hydrogen-bonding interaction is present which, together with secondary hydrogen bonding results in the formation of mostly two-dimensional network structures, exceptions being with compounds 4 and 5 (one-dimensional) and compound 6 (three-dimensional). In only two cases [compounds 1 and 4], are weak cation-anion or cation-cation π-π interactions found while weak aromatic C-H…O interactions are insignificant. The study shows that all compounds fit the previously formulated classification scheme for primary and secondary interactive modes for proton-transfer compounds of 3,5-dinitrosalicylic acid but there are some unusual variants

Evaluation quantitative des résidus de pyréthrinoïdes, d’aminophosphate et de triazines en zones de production de coton au Bénin par la méthode ELISA en phase liquide: Cas des eaux de la rivière Agbado

Le présent travail réalisé au Bénin dans la commune de Savalou, a consisté en une recherche de résidus de pyréthrinoïdes, d’aminophosphates et de triazines dans l’eau et les sédiments de la rivière Agbado par la technique ELISA (Enzyme-Linked Immuno Sorbent Assay) en phase liquide. Quatre campagnes d’échantillonnage ont été menées dont deux en saison sèche et deux en saison pluvieuse. Au total quatre sites d’échantillonnage ont été explorés. Il s’agit de Mèdétèkpo, du Barrage de la Société des Eaux du Bénin, de la Station de traitement d’eau et du grand pont de Gobada. En saison sèche, aucun des résidus recherchés n’a été détecté dans l’eau. Dans les sédiments, les teneurs varient de 0,10 à 0,39 ppb pour le glyphosate et de 0,22 à 0,97 ppb pour l’atrazine. En saison pluvieuse, dans l’eau, les taux varient de 0,05 ppb à 0,475 ppb pour l’atrazine, de 0,10 à 1,316 ppb pour le glyphosate et de 0,75 à 4,450 ppb pour les pyréthrinoïdes. Dans les sédiments seul le glyphosate a été détecté jusqu’à un taux de 8,62 ppb. En moyenne ces valeurs sont supérieures aux normes de qualité de l’eau de boisson admises par l’Union Européenne. Face à ces niveaux de contamination, il importe que des mesures correctives soient prises.Keywords: Contamination, eau, sédiments, Résidus de pesticide