Scavenger receptor control of chromogranin A-induced microglial stress and neurotoxic cascades

Chromogranin A (CgA), a neuroactive glycoprotein, is associated with microglial activation cascades implicated in neurodegeneration. Here we show that CgA-dependent inducible nitric oxide synthase (iNOS) expression and stress responses in microglia involved signalling via scavenger receptors (SR), since SR class-A (SR-A) ligands blocked iNOS expression, mitochondrial depolarisation, apoptosis and glutamate release. Furthermore, block of SR-A ameliorated CgA-induced microglial neurotoxicity. In contrast, block of CD36, or the receptor for advanced glycation end products (RAGE) did not prevent CgA-induced microglial activation and neurotoxicity. Thus, manipulation of specific scavenger receptor-coupled signalling pathways may provide avenues for therapeutic intervention in neurodegenerative diseases implicating microglial activation with chromogranin peptides.     

Resveratrol induces cell‐cycle disruption and apoptosis in chemoresistant B16 melanoma

Resveratrol, a naturally occurring polyphenol, has been shown to possess chemopreventive activities. In this study, we show that resveratrol (0–500 µM) inhibits the growth of a doxorubicin‐resistant B16 melanoma cell subline (B16/DOX) (IC₅₀ = 25 µM after 72 h, P < 0.05). This was accomplished by imposing an artificial checkpoint at the G₁–S phase transition, as demonstrated by cell‐cycle analysis and down‐regulation of cyclin D1/cdk4 and increased of p53 expression level. The G₁‐phase arrest of cell cycle in resveratrol‐treated (10–100 µM) B16/DOX cells was followed by the induction of apoptosis, which was revealed by pyknotic nuclei and fragmented DNA. Resveratrol also potentiated at subtoxic dose (25 µM for 24 h) doxorubicin cytotoxicity in the chemoresistant B16 melanoma (P < 0.01). When administered to mice, resveratrol (12.5 mg/kg) reduced the growth of an established B16/DOX melanoma and prolonged survival (32% compared to untreated mice). All these data support a potential use of resveratrol alone or in combination with other chemotherapeutic agents in the management of chemoresistant tumors. J. Cell. Biochem. 110: 893–902, 2010. © 2010 Wiley‐Liss, Inc.     

To have and not to have sex: When multiple evolutions of conditional use of sex elegantly solve the question in the ant genus Cataglyphis

Organisms use an amazingly large diversity of mechanisms to pass on their genes to the next generation. Sex is ancestral in eukaryotes, where it remains the most widespread way of reproduction. By combining one's genes with those of a partner, sex entails a dilution of one's genes at each generation. Evolution has been particularly creative in devising mechanisms allowing females to avoid this dilution, from classical parthenogenesis to the elimination of male genes after fertilization (Bell, 1982). Moreover, the term parthenogenesis includes various forms. Parthenogenesis can be used for female (thelytoky) or male (arrhenotoky) production and it can be associated with different cytological mechanisms, from strict clonality to meiotic division with the fusion of two of the four products of meiosis to restore diploidy (Suomalainen, Saura, & Lokki, 1987). Understanding the evolution of these diverse reproductive systems remains one of the most exciting and longstanding questions in evolutionary biology. By characterizing the reproductive systems of 11 species from the thermophilic ant genus Cataglyphis, in this issue of Molecular Ecology, Kuhn, Darras, Paknia, and Aron (2020) show the high lability of parthenogenesis, with multiple independent evolution of facultative thelytoky from sexual ancestors. The diversity of life history traits and social characteristics of this genus (e.g., mode of colony foundation, female polyandry) provides a unique and exciting opportunity to investigate the social and environmental factors driving the evolution of reproductive systems in social Hymenoptera.     

Regulation of a truncated isoform of AMP-activated protein kinase α (AMPKα) in response to hypoxia in the muscle of Pacific oyster Crassostrea gigas

AMP-activated protein kinase α (AMPKα) is a key regulator of energy balance in many model species during hypoxia. In a marine bivalve, the Pacific oyster Crassostrea gigas, we analyzed the protein content of adductor muscle in response to hypoxia during 6 h. In both smooth and striated muscles, the amount of full-length AMP-activated protein kinase α (AMPKα) remained unchanged during hypoxia. However, hypoxia induced a rapid and muscle-specific response concerning truncated isoforms of AMPKα. In the smooth muscle, a truncated isoform of AMPKα was increased from 1 to 6 h of hypoxia, and was linked with accumulation of AKT kinase, a key enzyme of the insulin signaling pathway which controls intracellular glucose metabolism. In this muscle, aerobic metabolism was maintained over the 6 h of hypoxia, as mitochondrial citrate synthase activity remained constant. In contrast, in striated muscle, hypoxia did not induce any significant modification of neither truncated AMPKα nor AKT protein content, and citrate synthase activity was altered after 6 h of hypoxia. Together, our results demonstrate that hypoxia response is specific to muscle type in Pacific oyster, and that truncated AMPKα and AKT proteins might be involved in maintaining aerobic metabolism in smooth muscle. Such regulation might occur in vivo during tidal intervals that cause up to 6 h of hypoxia.     

Self-assembled nucleolipids: from supramolecular structure to soft nucleic acid and drug delivery devices

This short review aims at presenting some recent illustrative examples of spontaneous nucleolipids self-assembly. High-resolution structural investigations reveal the diversity and complexity of assemblies formed by these bioinspired amphiphiles, resulting from the interplay between aggregation of the lipid chains and base-base interactions. Nucleolipids supramolecular assemblies are promising soft drug delivery systems, particularly for nucleic acids. Regarding prodrugs, squalenoylation is an innovative concept for improving efficacy and delivery of nucleosidic drugs.     

THE SEX-RATIO TRAIT IN DROSOPHILA SIMULANS: GEOGRAPHICAL DISTRIBUTION OF DISTORTION AND RESISTANCE

The sex-ratio trait we describe here in Drosophila simulans results from X-linked meiotic drive. Males bearing a driving X chromosome can produce a large excess of females (about 90%) in their progeny. This is, however, rarely the case in the wild, where resistance factors, including autosomal suppressors and insensitive Y chromosomes, prevent the expression of the driver. In this study, we searched for drive and resistance factors in strains of Drosophila simulans collected all over the world. Driving X chromosomes were found in all populations whenever a good sample size was available. Their frequency may reach up to 60%. However, the presence of driving X chromosomes never results in an excess of females, due to the systematic co-occurrence of resistance factors. The highest frequencies of driving X chromosomes were observed in islands, while populations from East and Central Africa (the supposed center of origin of the species) showed the highest level of resistance. The geographical pattern of drive and resistance factors, as well as the results of crosses between strains from different geographical areas, suggest that the sex-ratio system described here has a unique and ancient origin in the species.     

A gene encoding a germin-like protein,identified by a cDNA–AFLP approach,is specifically expressed during germination of<Emphasis Type="Italic"> Phaseolus vulgaris</Emphasis>

In order to identify markers of germination in Phaseolus vulgaris L., a cDNA-amplified fragment length polymorphism (AFLP) approach was conducted on mRNAs from embryo axes and from cotyledons. Among changes observed throughout the germination process, a cDNA fragment not detected 9 h after imbibition (HAI) but present specifically in axes 24 HAI was further studied. The complete cDNA was recovered by rapid amplification of cDNA ends, then cloned and sequenced. It includes an open reading frame predicting a 206-amino-acid polypeptide of 21.8 kDa. Analysis of the nucleotide sequence and deduced amino acid sequence revealed a high homology with germin-like proteins (GLPs), and particularly with an auxin-binding protein from peach, ABP19, that belongs to the GLP family. Thus, we propose that this cDNA encodes the first GLP described in P. vulgaris, designated PvGLP1. Northern blot analysis carried out on mRNAs from seed axes showed a dramatic increase in PvGLP1 expression a few hours before radicle emergence (17 HAI). Among mature vegetative tissues, PvGLP1 expression was very weak in pods and not detected in leaves, stems or roots. Immunoblot analysis using antibodies raised against AtGER3 from Arabidopsis thaliana showed that the protein could be detected only in axes from the dry seed stage onwards, at a steady-state level. Then, PvGLP1 expression seems to be associated with the early stages of embryo axis growth. The high homology indicated with ABP19 led us to study the effect of different concentrations of indole-3-acetic acid (IAA) on PvGLP1 expression during germination. Whereas no effect was noticed at low concentrations (1, 5, 10 microM), a marked decrease in PvGLP1 mRNA level was observed in axes of seeds imbibed with 100 microM IAA. Thus, PvGLP1 gene expression is not stimulated by auxin and, moreover, it might be inhibited by high concentrations of IAA.