Neurotoxicity in mice due to cysteine-rich parts of visna virus and HIV-1 Tat proteins

The trans-activating visna virus and HIV-1 Tat proteins share, at their amino-acid sequence level, a significant 60% analogy on 17 consecutive residues. These homologous sequences are also found in a part of the short neurotoxin sequence from snake venom. Synthetic peptides representative of the two analogous viral sequences are, after intracerebroventricular injection at doses of 200 micrograms per 20 g mouse, responsible for the death of the injected animal in few hours. The HIV-1 recombinant Tat protein has the same effect. Such observation suggests a direct role of the Tat lentiviral protein in the origin of the neurologic effects associated with visna and HIV-1 infections.     

Thermostability improvement of maltogenic amylase MAUS149 by error prone PCR

The thermostability of maltogenic amylase from Bacillus sp. US149 (MAUS149) was improved by random mutagenesis using error prone PCR. The library constructed for the mutants obtained was subjected to screening, leading to the selection of a thermostable mutant enzyme named MA-A27. The latter was noted to contain four single mutations, namely D46V, P78L, V145A, and K548E. The half-life times recorded for MA-A27 at 50 °C and 55 °C were 70 min and 25 min, compared to 30 min and 13 min for the wild type, respectively. The results from molecular modeling attributed the increase in thermostability observed for MA-A27 to P78L and K548E substitutions that led to new hydrogen bond and salt bridge formations. Further site-directed mutagenesis studies showed that the P78L and K548E single mutations underwent an increase in thermostability, thus confirming the joint contribution of both substitutions to the increase in thermostability observed for MA-A27.     

Ion channel activation by SPC3, a peptide derived from the HIV-1 gp120 V3 loop.

SPC3 is a multibranched peptide containing eight identical GPGRAF motifs which are derived from the human immunodeficiency virus (HIV)-1 gp120 V3 loop consensus sequence. This molecule was reported to prevent the infection of CD4+ cells by various HIV-1 and HIV-2 strains. However, the molecular mode of action of SPC3 remains unclear. Here, we investigated the possibility that SPC3 could interact with alpha/beta-chemokine receptors following observations that, first, the V3 loop is likely to be involved in alpha/beta-chemokine receptor-dependent HIV entry and, second, natural ligands of these receptors are potent inhibitors of cell infection. To address this point, we examined the effects of SPC3 on Xenopus oocytes either uninjected or expressing exogenous human CXCR4 alpha-chemokine receptors. Extracellular applications of micromolar concentrations of SPC3 onto Xenopus oocytes trigger potent inward chloride currents which can be inhibited by increasing extracellular Ca2+ concentration. This effect can be blocked by chloride channel antagonists and is highly specific to SPC3 as it is not triggered by structural analogs of SPC3. The SPC3-induced chloride conductance in oocytes is alpha/beta-chemokine receptor dependent because: (i) SPC3 alters the sensitivity of this channel to external applications of human recombinant MIP-1alpha, a natural ligand of human CCR5 receptor, and (ii) the amplitude of the inward current could be increased by the expression of exogenous human CXCR4 chemokine receptor. The effect of SPC3 appears to rely on the activation of a phospholipase A2 signaling pathway, but is not affected by changes in cytosolic Ca2+ concentration, or by alterations in Gi/Go protein, adenylate cyclase, phospholipase C or protein kinase C activity. Altogether, the data indicate that SPC3 is capable of activating a surface alpha/beta-chemokine-like receptor-mediated signaling pathway in competent cells, thereby triggering, either directly or indirectly, a Ca2+-inactivated chloride conductance.     

Nephroprotective effect of bee honey and royal jelly against subchronic cisplatin toxicity in rats

Cisplatin is one of the most potent and effective chemotherapeutic agents. However, its antineoplastic use is limited due to its cumulative nephrotoxic side effects. Therefore, the present study was undertaken to examine the nephroprotective potential of dietary bee honey and royal jelly against subchronic cisplatin toxicity in rats. Male Wistar rats were randomly divided into controls, cisplatin-treated, bee honey-pretreated cisplatin-treated and royal jelly-pretreated cisplatin-treated groups. Bee honey and royal jelly were given orally at doses of 20 and 100 mg/kg, respectively. Subchronic toxicity was induced by cisplatin (1 mg/kg bw, ip), twice weekly for 10 weeks. Cisplatin treated animals revealed a significant increase in serum level of renal injury products (urea, creatinine and uric acid). Histopathologically, cisplatin produced pronounced tubulointerstitial injuries, upregulated the fibrogenic factors, α-smooth muscle actin (α-SMA) and transforming growth factor β1(TGF-β1), and downregulated the cell proliferation marker, bromodeoxyuridine (Brdu). Dietary bee honey and royal jelly normalized the elevated serum renal injury product biomarkers, improved the histopathologic changes, reduced the expression of α-SMA and TGF-β1 and increased the expression of Brdu. Therefore, it could be concluded that bee honey, and royal jelly could be used as dietary preventive natural products against subchronic cisplatin-induced renal injury.     

Le noyau du gamète de l'Equisetum arvense L.

Résumé Les méthodes utilisées pour localiser, en microscopie électronique, les constituants du noyau du gamète mûr de l'Equisetum arvense L. montrent que:l'ADN, associé à une histone riche en arginine, se situe dans la zone centrale de l'organite; le nucléoplasme, renfermant une histone probablement riche en lysine, est réduit à une fine couche périphérique; l'ARN n'est plus identifiable; les protéines non-histone forment des massifs lenticulaires, accolés à la membrane nucléaire.

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The sperm of Equisetum arvense L. I. Ultrastructural and cytochemical studies of nuclear constituents of the ripe sperm

Summary Several ultrastructural cytochemical methods are used to determine the constituents of the ripe nucleus of Equisetum arvense L. They show that: DNA, associated with an arginine-rich histone, is localized in central region of the nucleus; nucleoplasm is reduced to a thin peripheral coat and contains a probably lysine rich histone; RNA is not detectable; non histone proteins form lenticular amounts disposed against the nuclear membrane.