The RNA-binding protein fragile X-related 1 regulates somite formation in Xenopus laevis

Fragile X-related 1 protein (FXR1P) is a member of a small family of RNA-binding proteins that includes the Fragile X mental retardation 1 protein (FMR1P) and the Fragile X-related 2 protein (FXR2P). These proteins are thought to transport mRNA and to control their translation. While FMR1P is highly expressed in neurons, substantial levels of FXR1P are found in striated muscles and heart, which are devoid of FMRP and FXR2P. However, little is known about the functions of FXR1P. We have isolated cDNAs for Xenopus Fxr1 and found that two specific splice variants are conserved in evolution. Knockdown of xFxr1p in Xenopus had highly muscle-specific effects, normal MyoD expression being disrupted, somitic myotomal cell rotation and segmentation being inhibited, and dermatome formation being abnormal. Consistent with the absence of the long muscle-specific xFxr1p isoform during early somite formation, these effects could be rescued by both the long and short mRNA variants. Microarray analyses showed that xFxr1p depletion affected the expression of 129 known genes of which 50% were implicated in muscle and nervous system formation. These studies shed significant new light on Fxr1p function(s).     

The stabilizability of a controlled system describing the dynamics of a fishery

This work presents two stock-effort dynamical models describing the evolution of a fish population growing and moving between two fishing zones, on which it is harvested by a fishing fleet, distributed on the two zones. The first model corresponds to the case of constant displacement rates of the fishing effort, and the second one to fish stock-dependent displacement rates. In equations of the fishing efforts, a control function is introduced as the proportion of the revenue to be invested, for each fleet. The stabilizability analysis of the aggregated model, in the neighborhood of the equilibrium point, enables the determination of a Lyapunov function, which ensures the existence of a stabilizing discontinuous feedback for this model. This enables us to control the system and to lead, in an uniform way, any solution of this system towards this desired equilibrium point.     

Comparative evaluation of the toxicity induced by mussels (Mytilus galloprovincialis) from two sites of the Moroccan Atlantic coast in mice

Atlantic coast in mice. Preliminary studies showed that seawater contains heavy metals from domestic, agricultural and industrial wastes. Marine bivalves concentrate these pollutants by filtration and serve as vectors in human exposure. The objective of this study was to determine the concentration of heavy metals; cadmium (Cd); chromium (Cr), and lead (Pb) in mussels (Mytilus galloprovincialis) collected in two coastal sites; Jorf Lasfar (JL) (neighbouring a phosphate processing platform) and Oualidia (OL) (a vegetable growing area) located at 120 and 190 km south of Casablanca, respectively. Another objective was to test and compare the toxicity of these mussels on mice. The results indicated the presence of heavy metals (Cd, Cr, and Pb) in mussels at different concentrations, depending on the collection period. Higher concentrations were obtained at JL than at OL: for example, Cd concentrations were 80 +/- 15 to 199 +/- 28 versus 23 +/- 5 microg/g mussel dry weight, respectively. Cramming with mussel powder did not increase Cd, Cr, or Pb concentration in either liver or kidneys of treated mice. The relative kidney weights were reduced. Increased glucose urea was observed in animals' urine. Treatment with mussels from OL induced significant reduction (20%) in mice body weight, together with an increase in creatinuria. These results indicate that mussels collected from OL are more harmful than those obtained from JL are. All these mussels should not be recommended for human consumption.     

Bigger is not always better: when brains get smaller

Many studies assume that an increase in brain size is beneficial. However, the costs of producing and maintaining a brain are high, and we argue that brain size should be secondarily reduced by natural selection whenever the costs outweigh the benefits. Our results confirm this by showing that brain size is subject to bidirectional selection. Relative to the ancestral state, brain size in bats has been reduced in fast flyers, while it has increased in manoeuvrable flyers adapted to flight in complex habitats. This study emphasizes that brain reduction and enlargement are equally important, and they should both be considered when investigating brain size evolution.     

Role of NK cell-activating receptors and their ligands in the lysis of mononuclear phagocytes infected with an intracellular bacterium

We studied the role of NK cell-activating receptors and their ligands in the lysis of mononuclear phagocytes infected with the intracellular pathogen Mycobacterium tuberculosis. Expression of the activating receptors NKp30, NKp46, and NKG2D were enhanced on NK cells by exposure to M. tuberculosis-infected monocytes, whereas expression of DNAX accessory molecule-1 and 2B4 was not. Anti-NKG2D and anti-NKp46 inhibited NK cell lysis of M. tuberculosis-infected monocytes, but Abs to NKp30, DNAX accessory molecule-1, and 2B4 had no effect. Infection of monocytes up-regulated expression of the NKG2D ligand, UL-16 binding protein (ULBP)1, but not expression of ULBP2, ULBP3, or MHC class I-related chain A or chain B. Up-regulation of ULBP1 on infected monocytes was dependent on TLR2, and anti-ULBP1 abrogated NK cell lysis of infected monocytes. The dominant roles of NKp46, NKG2D, and ULBP1 were confirmed for NK cell lysis of M. tuberculosis-infected alveolar macrophages. We conclude that NKp46 and NKG2D are the principal receptors involved in lysis of M. tuberculosis-infected mononuclear phagocytes, and that ULBP1 on infected cells is the major ligand for NKG2D. Furthermore, TLR2 contributes to up-regulation of ULBP1 expression.     

NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol

The discovery of autosomal dominant hypercholesterolemic patients with mutations in the PCSK9 gene, encoding the proprotein convertase NARC-1, resulting in the missense mutations suggested a role in low density lipoprotein (LDL) metabolism. We show that the endoplasmic reticulum-localized proNARC-1 to NARC-1 zymogen conversion is Ca2+-independent and that within the zymogen autocatalytic processing site SSVFAQ [downward arrow]SIP Val at P4 and Pro at P3' are critical. The S127R and D374Y mutations result in approximately 50-60% and > or =98% decrease in zymogen processing, respectively. In contrast, the double [D374Y + N157K], F216L, and R218S natural mutants resulted in normal zymogen processing. The cell surface LDL receptor (LDLR) levels are reduced by 35% in lymphoblasts of S127R patients. The LDLR levels are also reduced in stable HepG2 cells overexpressing NARC-1 or its natural mutant S127R, and this reduction is abrogated in the presence of 5 mm ammonium chloride, suggesting that overexpression of NARC-1 increases the turnover rate of the LDLR. Adenoviral expression of wild type human NARC-1 in mice resulted in a maximal approximately 9-fold increase in circulating LDL cholesterol, while in LDLR-/- mice a delayed approximately 2-fold increase in LDL cholesterol was observed. In conclusion, NARC-1 seems to affect both the level of LDLR and that of circulating apoB-containing lipoproteins in an LDLR-dependent and -independent fashion.     

FGF6 mediated expansion of a resident subset of cells with SP phenotype in the C2C12 myogenic line

Fibroblast growth factor 6 (FGF6) is selectively expressed during muscle development and regeneration. We examined its effect on muscle precursor cells (mpc) by forcing stable FGF6 expression in C2C12 cells in vitro. FGF6 produced in genetically engineered mpc was active, inducing strong morphological changes, altering cell adhesion and compromising their ability to differentiate into myotubes. Expression of MyoD and myogenin, but not of Myf5, was abrogated in FGF6 engineered mpc. These effects were reversed by FGF inhibitors. Ectopic expression of MyoD also restored fiber formation indicating that FGF6 interferes with the myogenic differentiation pathway upstream of MyoD. We also report that in the presence of FGF6, the minor (0.5-2%) subpopulation of cells actively excluding Hoechst 33342 in a verapamil-dependent manner (SP phenotype) was increased to 15-20% and the expression of the mdr1a gene (but not mdr1b) was upregulated by 400-fold. Our data establish a previously undescribed link between FGF6--a muscle specific growth factor--and a multidrug resistance gene expressed in stem cells, and suggest a role for FGF6 in the maintenance of a reserve pool of progenitor cells in the skeletal muscle.     

Synthesis and characterization of immunogens based on calix[4]arene-crown-6 for the generation of antibodies directed towards cesium ions

With the aim of generating antibodies directed towards cesium, a calix[4]arene-crown-6 in the 1,3-alternate conformation bearing an N-hydroxysuccinimide function was synthesized. The calixarene was coupled to bovine serum albumin using different calixarene/protein ratios, and cesium was loaded. Conjugates were characterized using trinitrobenzenesulfonic acid derivatization, matrix assisted laser desorption ionisation-mass spectrometry (MALDI-TOF-MS), and inductively coupled plasma-mass spectrometry (ICP-MS). Targeted lysines were determined after enzymatic cleavage followed by MALDI-TOF-MS, and a progressive targeting related to lysines accessibility was observed.