NOX enzymes: potential target for the treatment of acute lung injury

Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), is characterized by acute inflammation, disruption of the alveolar-capillary barrier, and in the organizing stage by alveolar pneumocytes hyperplasia and extensive lung fibrosis. The cellular and molecular mechanisms leading to the development of ALI/ARDS are not completely understood, but there is evidence that reactive oxygen species (ROS) generated by inflammatory cells as well as epithelial and endothelial cells are responsible for inflammatory response, lung damage, and abnormal repair. Among all ROS-producing enzymes, the members of NADPH oxidases (NOXs), which are widely expressed in different lung cell types, have been shown to participate in cellular processes involved in the maintenance of lung integrity. It is not surprising that change in NOXs' expression and function is involved in the development of ALI/ARDS. In this context, the use of NOX inhibitors could be a possible therapeutic perspective in the management of this syndrome. In this article, we summarize the current knowledge concerning some cellular aspects of NOXs localization and function in the lungs, consider their contribution in the development of ALI/ARDS and discuss the place of NOX inhibitors as potential therapeutical target.     

Marine biodiversity on the Algerian Continental Shelf (Mediterranean Sea)

The Mediterranean Sea is known as a biodiversity hot spot, with 16,848 species reported. Biodiversity is higher in coastal areas and decreases with depth. However, knowledge about the southwestern sector remains scarce. For the last three decades, sampling of soft-bottom communities along the 1180 km of the shallow Algerian coast (0–136 m) has recorded 1642 macrobenthic species. There is a decreasing west–east species-richness gradient, especially for the total species richness and the amphipods. In addition, quantitative sampling in Bou Ismail Bay in summer 1988 (98 sampling sites for a total of 841 species) shows that diversity indices (i.e. species richness, >100 species for 0.2 m^?2; Shannon diversity, >6.0; and ES₅₀, >34) are among the highest for similar sand and muddy-fine sand communities in the Mediterranean Sea and the northeastern Atlantic Ocean. Bou Ismail Bay appears to have the highest species richness among Algerian bays, probably because of its variety of benthic habitats and the absence of significant pollution in this area. Monitoring must be undertaken to survey this high biodiversity, and a national strategy should be proposed to preserve high diversity zones.     

Shiga toxin induces tubular membrane invaginations for its uptake into cells

Clathrin seems to be dispensable for some endocytic processes and, in several instances, no cytosolic coat protein complexes could be detected at sites of membrane invagination. Hence, new principles must in these cases be invoked to account for the mechanical force driving membrane shape changes. Here we show that the Gb3 (glycolipid)-binding B-subunit of bacterial Shiga toxin induces narrow tubular membrane invaginations in human and mouse cells and model membranes. In cells, tubule occurrence increases on energy depletion and inhibition of dynamin or actin functions. Our data thus demonstrate that active cellular processes are needed for tubule scission rather than tubule formation. We conclude that the B-subunit induces lipid reorganization that favours negative membrane curvature, which drives the formation of inward membrane tubules. Our findings support a model in which the lateral growth of B-subunit-Gb3 microdomains is limited by the invagination process, which itself is regulated by membrane tension. The physical principles underlying this basic cargo-induced membrane uptake may also be relevant to other internalization processes, creating a rationale for conceptualizing the perplexing diversity of endocytic routes.     

Neuroprotective effects of the gliopeptide ODN in an in vivo model of Parkinson’s disease

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a progressive loss of dopamine (DA) neurons through apoptotic, inflammatory and oxidative stress mechanisms. The octadecaneuropeptide (ODN) is a diazepam-binding inhibitor (DBI)-derived peptide, expressed by astrocytes, which protects neurons against oxidative cell damages and apoptosis in an in vitro model of PD. The present study reveals that a single intracerebroventricular injection of 10 ng ODN 1 h after the last administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) prevented the degeneration of DA neurons induced by the toxin in the substantia nigra pars compacta of mice, 7 days after treatment. ODN-mediated neuroprotection was associated with a reduction of the number of glial fibrillary acidic protein-positive reactive astrocytes and a strong inhibition of the expression of pro-inflammatory genes such as interleukins 1β and 6, and tumor necrosis factor-α. Moreover, ODN blocked the inhibition of the anti-apoptotic gene Bcl-2, and the stimulation of the pro-apoptotic genes Bax and caspase-3, induced by MPTP in the substantia nigra pars compacta. ODN also decreased or even in some cases abolished MPTP-induced oxidative damages, overproduction of reactive oxygen species and accumulation of lipid oxidation products in DA neurons. Furthermore, DBI knockout mice appeared to be more vulnerable than wild-type animals to MPTP neurotoxicity. Taken together, these results show that the gliopeptide ODN exerts a potent neuroprotective effect against MPTP-induced degeneration of nigrostriatal DA neurons in mice, through mechanisms involving downregulation of neuroinflammatory, oxidative and apoptotic processes. ODN may, thus, reduce neuronal damages in PD and other cerebral injuries involving oxidative neurodegeneration.     

Geology and palaeontology of the Upper Miocene Toros-Menalla hominid locality,Chad

All six known specimens of the early hominid Sahelanthropus tchadensis come from Toros-Menalla site 266 (TM 266), a single locality in the Djurab Desert, northern Chad, central Africa. Here we present a preliminary analysis of the palaeontological and palaeoecological context of these finds. The rich fauna from TM 266 includes a significant aquatic component such as fish, crocodiles and amphibious mammals, alongside animals associated with gallery forest and savannah, such as primates, rodents, elephants, equids and bovids. The fauna suggests a biochronological age between 6 and 7 million years. Taken together with the sedimentological evidence, the fauna suggests that S. tchadensis lived close to a lake, but not far from a sandy desert, perhaps the oldest record of desert conditions in the Neogene of northern central Africa.     

Induction of somatic hypermutation in immunoglobulin genes is dependent on DNA polymerase iota

Somatic hypermutation of immunoglobulin genes is a unique, targeted, adaptive process. While B cells are engaged in germinal centres in T-dependent responses, single base substitutions are introduced in the expressed Vh/Vl genes to allow the selection of mutants with a higher affinity for the immunizing antigen. Almost every possible DNA transaction has been proposed to explain this process, but each of these models includes an error-prone DNA synthesis step that introduces the mutations. The Y family of DNA polymerases--pol eta, pol iota, pol kappa and rev1--are specialized for copying DNA lesions and have high rates of error when copying a normal DNA template. By performing gene inactivation in a Burkitt's lymphoma cell line inducible for hypermutation, we show here that somatic hypermutation is dependent on DNA polymerase iota.     

Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome

We took advantage of overlapping interstitial deletions at chromosome 8p11-p12 in two individuals with contiguous gene syndromes and defined an interval of roughly 540 kb associated with a dominant form of Kallmann syndrome, KAL2. We establish here that loss-of-function mutations in FGFR1 underlie KAL2 whereas a gain-of-function mutation in FGFR1 has been shown to cause a form of craniosynostosis. Moreover, we suggest that the KAL1 gene product, the extracellular matrix protein anosmin-1, is involved in FGF signaling and propose that the gender difference in anosmin-1 dosage (because KAL1 partially escapes X inactivation) explains the higher prevalence of the disease in males.     

Role of NMDA receptors in adult neurogenesis: an ontogenetic (re)view on activity-dependent development

It is now widely accepted that neurogenesis continues throughout life. Accumulating evidence suggests that neurotransmitters are essential signaling molecules that control the different steps of neurogenesis. Nevertheless, we are only beginning to understand the precise role of neurotransmitter receptors and in particular excitatory glutamatergic transmission in the differentiation of adult-born neurons. Recent technical advances allow single-cell gene deletion to study cell-autonomous effects during the maturation of adult-born neurons. Single-cell gene deletion overcomes some of the difficulties in interpreting global gene deletion effects on entire brain areas or systemic pharmacological approaches that might result in compensatory circuit effects. The aim of this review is to summarize recent advances in the understanding of the role of NMDA receptors (NMDARs) during the differentiation of adult-born neurons and put them in perspective with previous findings on cortical development.