Zoledronate Effects on Systemic and Jaw Osteopenias in Ovariectomized Periostin-Deficient Mice

Osteoporosis and periodontal disease (PD) are frequently associated in the elderly, both concurring to the loss of jaw alveolar bone and finally of teeth. Bisphosphonates improve alveolar bone loss but have also been associated with osteonecrosis of the jaw (ONJ), particularly using oncological doses of zoledronate. The effects and therapeutic margin of zoledronate on jaw bone therefore remain uncertain. We reappraised the efficacy and safety of Zoledronate (Zol) in ovariectomized (OVX) periostin (Postn)-deficient mice, a unique genetic model of systemic and jaw osteopenia. Compared to vehicle, Zol 1M (100 µg/kg/month) and Zol 1W (100 µg/kg/week) for 3 months both significantly improved femur BMD, trabecular bone volume on tissue volume (BV/TV) and cortical bone volume in both OVX Postn^+/+ and Postn^−/− (all p<0.01). Zol 1M and Zol 1W also improved jaw alveolar and basal BV/TV, although the highest dose (Zol 1W) was less efficient, particularly in Postn^−/−. Zol decreased osteoclast number and bone formation indices, i.e. MAR, MPm/BPm and BFR, independently in Postn^−/− and Postn^+/+, both in the long bones and in deep jaw alveolar bone, without differences between Zol doses. Zol 1M and Zol 1W did not reactivate inflammation nor increase fibrous tissue in the bone marrow of the jaw, whereas the distance between the root and the enamel of the incisor (DRI) remained high in Postn^−/− vs Postn^+/+ confirming latent inflammation and lack of crestal alveolar bone. Zol 1W and Zol 1M decreased osteocyte numbers in Postn^−/− and Postn^+/+ mandible, and Zol 1W increased the number of empty lacunae in Postn^−/−, however no areas of necrotic bone were observed. These results demonstrate that zoledronate improves jaw osteopenia and suggest that in Postn^−/− mice, zoledronate is not sufficient to induce bone necrosis.     

Mass distributions of a macromolecular assembly based on electrospray ionization mass spectrometric masses of the constituent subunits

Macromolecular assemblies containing multiple protein subunits and having masses in the megadalton (MDa) range are involved in most of the functions of a living cell. Because of variation in the number and masses of subunits, macromolecular assemblies do not have a unique mass, but rather a mass distribution. The giant extracelular erythrocruorins (Ers), ∼ 3.5 MDa, comprized of at least 180 polypeptide chains, are one of the best characterized assemblies. Three-dimensional reconstructions from cryoelectron microscopic images show them to be hexagonal bilayer complexes of 12 subassemblies, each comprised of 12 globin chains, anchored to a subassembly of 36 nonglobin linker chains. We have calculated the most probable mass distributions forLumbricus andRiftia assemblies and their globin and linker subassemblies, based on theLumbricus Er stoichiometry and using accurate subunit masses obtained by electrospray ionization mass spectrometry. The expected masses ofLumbricus andRiftia Ers are 3.517 MDa and 3.284 MDa, respectively, with a possible variation of ∼ 9% due to the breadth of the mass distributions. TheLumbricus Er mass is in astonishingly good agreement with the mean of 23 known masses, 3.524 ± 0.481 MDa.     

Aeroecology meets aviation safety: early warning systems in Europe and the Middle East prevent collisions between birds and aircraft

The aerosphere is utilized by billions of birds, moving for different reasons and from short to great distances spanning tens of thousands of kilometres. The aerosphere, however, is also utilized by aviation which leads to increasing conflicts in and around airfields as well as en‐route. Collisions between birds and aircraft cost billions of euros annually and, in some cases, result in the loss of human lives. Simultaneously, aviation has diverse negative impacts on wildlife. During avian migration, due to the sheer numbers of birds in the air, the risk of bird strikes becomes particularly acute for low‐flying aircraft, especially during military training flights. Over the last few decades, air forces across Europe and the Middle East have been developing solutions that integrate ecological research and aviation policy to reduce mutual negative interactions between birds and aircraft. In this paper we 1) provide a brief overview of the systems currently used in military aviation to monitor bird migration movements in the aerosphere, 2) provide a brief overview of the impact of bird strikes on military low‐level operations, and 3) estimate the effectiveness of migration monitoring systems in bird strike avoidance. We compare systems from the Netherlands, Belgium, Germany, Poland and Israel, which are all areas that Palearctic migrants cross twice a year in huge numbers. We show that the en‐route bird strikes have decreased considerably in countries where avoidance systems have been implemented, and that consequently bird strikes are on average 45% less frequent in countries with implemented avoidance systems in place. We conclude by showing the roles of operational weather radar networks, forecast models and international and interdisciplinary collaboration to create safer skies for aviation and birds.     

Trapping of human DNA topoisomerase I by DNA structures mimicking intermediates of DNA repair

In this report we show that human DNA Topoisomerase I (Top1) forms DNA-protein adducts with nicked and gapped DNA structures lacking a conventional Top1 cleavage site. The radioactively labeled crosslinking products were identified by SDS-gel electrophoresis. The chemical structure of the groups at 5' or 3' end of the nick does not have an effect on the formation of these covalent adducts. Therefore, all kinds of nicks, either directly induced by ionizing radiation or reactive oxygen species or indirectly induced in the course of base excision repair (BER) are targets for Top1 that competes with BER proteins and other nick-sensors. Top1-DNA covalent adducts formed in cells exposed to DNA damaging agents can promote genetic instability.     

Threats to and conservation of North African wetlands: the case of the Ramsar site of Beni-Belaid (NE Algeria)

Because of their biogeographical and geomorphological context, the northeastern Algeria wetlands present high species and community richness. The vegetation study of the Ramsar site of Beni-Belaid (Kabylia) showed the existence of four main communities, distributed along gradients of hydrology and disturbance. The obtained results reveal worrying threats on short term: overgrazing results in the lake invasion by the sand eroded from the coastal dune; agriculture induces illegal cutting, water pollution and excessive groundwater pumping; finally, hunting and fishing are illegally practiced into the Ramsar site. The awareness of public authorities is needed in order: (1) to completely protect the wetland with the aim of restoring a riparian forest belt; and (2) to initiate a campaign for increasing the local population awareness, and its involvement in conservation programs.     

7-Ketocholesterol Incorporation into Sphingolipid/Cholesterol-enriched (Lipid Raft) Domains Is Impaired by Vitamin E: A SPECIFIC ROLE FOR ��-TOCOPHEROL WITH CONSEQUENCES ON CELL DEATH*

Cholesterol oxides, in particular 7-ketocholesterol, are proatherogenic compounds that induce cell death in the vascular wall when localized in lipid raft domains of the cell membrane. Deleterious effects of 7-ketocholesterol can be prevented by vitamin E, but the molecular mechanism involved is unclear. In this study, unlike γ-tocopherol, the α-tocopherol vitamin E form was found to prevent 7-ketocholesterol-mediated apoptosis of A7R5 smooth muscle cells. To be operative, α-tocopherol needed to be added to the cells before 7-ketocholesterol, and its anti-apoptotic effect was reduced and even suppressed when added together or after 7-ketocholesterol, respectively. Both pre- and co-treatment of the cells with α-tocopherol resulted in the redistribution of 7-ketocholesterol out of the sphingolipid/cholesterol-enriched (lipid raft) domains. In turn, fewer amounts of α-tocopherol associated with lipid rafts on 7-ketocholesterol-pretreated cells compared with untreated cells, with no prevention of cell death in this case. In further support of the implication of lipid raft domains, the dephosphorylation/inactivation of Akt-PKB was involved in the 7-ketocholesterol-induced apoptosis. Akt-PKB dephosphorylation was prevented by α-tocopherol, but not γ-tocopherol pretreatment.It has been suggested that cholesterol oxide-induced apoptosis is a key event in the initiation and progression of atherosclerosis lesions (1, 2). In the initial step of the disease, cholesterol oxides in modified low density lipoproteins were found to promote the death of endothelial cells lining the intravascular lumen (1, 2). In more advanced stages and as the atherosclerotic lesion progresses, cholesterol oxides could also contribute to the destruction of foam cells and vascular smooth muscle cells, to the formation of the lipid core, to the reduction of cell proliferation, and eventually to plaque destabilization (1, 2). Among cholesterol oxides that are mainly synthesized during oxidation of low density lipoproteins, 7-ketocholesterol is one of the most abundant in plasma and atherosclerotic lesions (3). Moreover, in a number of cell models, it has been established that 7-ketocholesterol is one of the cholesterol oxide derivatives with the highest pro-apoptotic potential (4, 5). The 7-ketocholesterol derivative associates preferentially with membrane lipid raft domains (6), which are characterized by the lateral packing of glycosphingolipids, sphingolipids, and cholesterol. Because of their insolubility in cold non-ionic detergents, rafts are also called detergent-resistant membranes (7). These structures are thought to be involved in cellular signaling mechanisms (8, 9). It is worthy of note that 7-ketocholesterol has been shown to induce cell death through inactivation of the phosphatidylinositol 3-kinase/Akt signaling pathway (10), which is known to be highly specific to lipid raft domains (9).Vitamin E is composed of closely related molecules, i.e. tocopherols and tocotrienols, which are each composed of four α, β, γ, and δ analogues. Although vitamin E was widely studied for its ability to prevent cellular damage by reactive oxygen species, it has recently been the subject of intense research for its putative, non-antioxidant functions (11, 12). Among the various forms of vitamin E, α-tocopherol is most abundant in the body as it is specifically recognized by the liver α-tocopherol transfer protein. Although several studies have shown that vitamin E has the ability to counteract the pro-apoptotic effect of 7-ketocholesterol in cultured cells (10, 13), the underlying molecular mechanism is unclear.In the present study the molecular mechanism involved in the vitamin E-mediated protection against apoptosis induced by 7-ketocholesterol was investigated on the well known A7R5 aortic smooth muscle cell model. It is reported here that α-tocopherol, but not γ-tocopherol, effectively protects the cells against 7-ketocholesterol-induced apoptosis when applied as a pretreatment before the addition of 7-ketocholesterol. Unlike γ-tocopherol, α-tocopherol was able to activate the Akt-PKB anti-apoptotic signaling pathway in the lipid raft domains (14), leading to phosphorylation and, thus, inactivation of Bad (15). Most importantly, the protective effect of α-tocopherol is shown to operate through its prior incorporation into the lipid raft domains of the plasma membrane, which leads to the subsequent exclusion and, thus, inactivation of 7-ketocholesterol.     

Présence de l’éocrinoïde Ascocystites Barrande (Echinodermata,Blastozoa) dans l’Ordovicien supérieur (Caradoc) de l’Anti-Atlas (Maroc) : premières données

Family Ascocystitidae, defined and established by Georges Ubaghs in 1967, includes a single genus, Ascocystites. This genus was described and figured for the first time by Barrande in 1887, from Bohemian specimens. Thereafter, specimens brought close to Ascocystites or assigned to this genus were described starting from samples collected in Bohemia in the Armorican Massif or in Portugal. The new specimens were collected in Morocco in the Eastern Anti-Atlas, within the formation of Izzeguirene of Caradoc age. The studied material includes several sandy slabes often containing many well-preserved and almost complete individuals. These levels gather individuals of various sizes, corresponding to various stages of development. The morphological study in progress should allow a specific attribution by comparison with the Bohemian and Armorican forms actually known. The Moroccan material has, in addition, the advantage of corresponding to associations of several Echinodermata groups, rich in individuals, allowing a taphonomic and possibly paleoenvironmental study. Biostratigraphically, Ascocystitidae are actually known between Middle (Armorican Massif and Portugal) and Upper Ordovician (Bohemia and now Morocco). The discovery of Ascocystitidae in the Moroccan Anti-Atlas extends their distribution, within gondwanian domain, during Middle and Upper Ordovician.     

Nutritional metabonomics: applications and perspectives

Nowadays, nutrition focuses on improving health of individuals through diet. Current nutritional research aims at health promotion, disease prevention, and performance improvement. Modern analytical platforms allow the simultaneous measurement of multiple metabolites providing new insights in the understanding of the functionalities of cells and whole organisms. Metabonomics, "the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modifications", provides a systems approach to understanding global metabolic regulations of organisms. This concept has arisen from various applications of NMR and MS spectroscopies to study the multicomponent metabolic composition of biological fluids, cells, and tissues. The generated metabolic profiles are processed by multivariate statistics to maximize the recovery of information to be correlated with well-determined stimuli such as dietary intervention or with any phenotypic data or diet habits. Metabonomics is thus uniquely suited to assess metabolic responses to deficiencies or excesses of nutrients and bioactive components. Furthermore, metabonomics is used to characterize the metabolic phenotype of individuals integrating genetic polymorphism, metabolic interactions with commensal and symbiotic partners such as gut microflora, as well as environmental and behavioral factors including dietary preferences. This paper reports several experimental key aspects in nutritional metabonomics, reviews its applications employing targeted and holistic approach analysis for the study of the metabolic responses following dietary interventions. It also reports the assessment of intra- and inter-individual variability in animal and human populations. The potentialities of nutritional metabonomics for the discovery of new biomarkers and the characterization of metabolic phenotypes are discussed in a context of their possible utilizations for personalized nutrition to provide health maintenance at the individual level.