Differentiated influence of off-road and on-road cycling practice on balance control and the related-neurosensory organization

This study aimed to determine the sensorimotor strategies privileged by mountain bikers (MTB) and road cyclists (RC) for balance control. Twenty-four MTB and 24 RC (off-road Olympics, world, continental and national champions, Tour-de-France participants, on-road world cup race winner) volunteered to answer a questionnaire about the characteristics of cycling practice and perform a sensory organization test, aiming to evaluate balance control in 6 different sensory situations based upon visual and support surface perturbations (C1^ES to C6^ES). RC balance performances were better than those of MTB both during quiet stance eyes opened (C1^ES, p = 0.011) and when only somatosensory information is disrupted (C4^ES, p = 0.039), highlighting a higher use of vision to control balance in RC. Moreover, a positive correlation was shown in the whole population (MTB + RC) between the visual ratio (R^VIS = C4^ES/C1^ES) and the proportion of riding distance of on-road cycling (ρ = 0.28, p = 0.054). In MTB, the use of proprioception (somatosensory ratio: R^SOM = C2^{ES(eyes closed)}/C1^ES) was increased by a higher intensity of off-road cycling (ρ = 0.49, p = 0.018) and that of vision (R^VIS) by a higher intensity of on-road cycling (ρ = 0.41, p = 0.048). The difference in sensory organization between MTB and RC could be explained by adaptive processes elaborated from environmental stimulations and technical specificities of these disciplines.     

ADAM function in embryogenesis

Cleavage of proteins inserted into the plasma membrane (shedding) is an essential process controlling many biological functions including cell signaling, cell adhesion and migration as well as proliferation and differentiation. ADAM surface metalloproteases have been shown to play an essential role in these processes. Gene inactivation during embryonic development have provided evidence of the central role of ADAM proteins in nematodes, flies, frogs, birds and mammals. The relative contribution of four subfamilies of ADAM proteins to developmental processes is the focus of this review.     

Post-release survey to assess impact and potential host range expansion by Amitus hesperidum and Encarsia perplexa, two parasitoids introduced for the biological control of the citrus blackfly, Aleurocanthus woglumi in Dominica

Four years after the release of two exotic parasitoids, Amitus hesperidum Silvestri (Hymenoptera: Platygasteridae) and Encarsia perplexa Huang and Polaszek (Hymenoptera: Aphelinidae) for the classical biological control of the citrus blackfly (CBF), Aleurocanthus woglumi Ashby (Hemiptera: Aleyrodidae) in Dominica, a survey was conducted to assess establishment as well as potential nontarget effects especially on Aleyrodidae and other related taxa. CBF populations were low to non-existent in 50 of 51 field sites examined. At the site where CBF was encountered, both E. perplexa and A. hesperidum were present and CBF populations were declining. The two parasitoids were not among the several species collected on nontarget Aleryodidae and Hemiptera. It is concluded that E. perplexa and A. hesperidum have kept CBF populations under effective biological control in Dominica and there is no evidence of any nontarget effects on other Aleyrodidae or their natural enemies. Handling Editor: Dirk Babendreier.     

Deficiency of Dol-P-Man Synthase Subunit DPM3 Bridges the Congenital Disorders of Glycosylation with the Dystroglycanopathies

Alpha-dystroglycanopathies such as Walker Warburg syndrome represent an important subgroup of the muscular dystrophies that have been related to defective O-mannosylation of alpha-dystroglycan. In many patients, the underlying genetic etiology remains unsolved. Isolated muscular dystrophy has not been described in the congenital disorders of glycosylation (CDG) caused by N-linked protein glycosylation defects. Here, we present a genetic N-glycosylation disorder with muscular dystrophy in the group of CDG type I. Extensive biochemical investigations revealed a strongly reduced dolichol-phosphate-mannose (Dol-P-Man) synthase activity. Sequencing of the three DPM subunits and complementation of DPM3-deficient CHO2.38 cells showed a pathogenic p.L85S missense mutation in the strongly conserved coiled-coil domain of DPM3 that tethers catalytic DPM1 to the ER membrane. Cotransfection experiments in CHO cells showed a reduced binding capacity of DPM3(L85S) for DPM1. Investigation of the four Dol-P-Man-dependent glycosylation pathways in the ER revealed strongly reduced O-mannosylation of alpha-dystroglycan in a muscle biopsy, thereby explaining the clinical phenotype of muscular dystrophy. This mild Dol-P-Man biosynthesis defect due to DPM3 mutations is a cause for alpha-dystroglycanopathy, thereby bridging the congenital disorders of glycosylation with the dystroglycanopathies.     

mtDNA and Y-chromosome variation in the Talysh of Iran and Azerbaijan

The Northern Talysh from Azerbaijan and the Southern Talysh from Iran self‐identify as one ethnic group and speak a Northwestern Iranian language. However, the Northern and Southern Talysh dialects are so different that they may actually be separate languages. Does this linguistic differentiation reflect internal change due to isolation, or could contact‐induced change have played a role? We analyzed mtDNA HVI sequences, 11 Y‐chromosome bi‐allelic markers, and 9 Y‐STR loci in Northern and Southern Talysh and compared them with their neighboring groups. The mtDNA data show a close relatedness of both groups with each other and with neighboring groups, whereas the Northern Talysh Y‐chromosome variation differs from that of neighboring groups, probably as a result of genetic drift. This genetic drift most likely reflects a founder event in the male gene pool of Northern Talysh: either fewer males than females migrated to Azerbaijan, or there was a higher degree of relatedness among the male migrants. Since we find no evidence of substantial genetic contact between either Northern or Southern Talysh and neighboring groups, we conclude that internal change, rather than contact‐induced change, most likely explains the linguistic differentiation between Northern and Southern Talysh. Am J Phys Anthropol, 2009. © 2008 Wiley‐Liss, Inc.     

Impact of environmental stress on aphid clonal resistance to parasitoids: Role of Hamiltonella defensa bacterial symbiosis in association with a new facultative symbiont of the pea aphid

Resistance to endoparasitoids in aphids involves complex interactions between insect and microbial players. It is now generally accepted that the facultative bacterial symbiont Hamiltonella defensa of the pea aphid Acyrthosiphon pisum is implicated in its resistance to the parasitoid Aphidius ervi. It has also been shown that heat negatively affects pea aphid resistance, suggesting the thermosensitivity of its defensive symbiosis. Here we examined the effects of heat and UV-B on the resistance of A. pisum to A. ervi and we relate its stability under heat stress to different facultative bacterial symbionts hosted by the aphid. For six A. pisum clones harboring four different facultative symbiont associations, the impact of heat and UV-B was measured on their ability to resist A. ervi parasitism under controlled conditions. The results revealed that temperature strongly affected resistance, while UV-B did not. As previously shown, highly resistant A. pisum clones singly infected with H. defensa became more susceptible to parasitism after exposure to heat. Interestingly, clones that were superinfected with H. defensa in association with a newly discovered facultative symbiont, referred to as PAXS (pea aphid X-type symbiont), not only remained highly resistant under heat stress, but also expressed previously unknown, very precocious resistance to A. ervi compared to clones with H. defensa alone. The prevalence of dual symbiosis involving PAXS and H. defensa in local aphid populations suggests its importance in protecting aphid immunity to parasitoids under abiotic stress.     

Relative Contributions of Cystathionine ��-Synthase and ��-Cystathionase to H2S Biogenesis via Alternative Trans-sulfuration Reactions

In mammals, the two enzymes in the trans-sulfuration pathway, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), are believed to be chiefly responsible for hydrogen sulfide (H₂S) biogenesis. In this study, we report a detailed kinetic analysis of the human and yeast CBS-catalyzed reactions that result in H₂S generation. CBS from both organisms shows a marked preference for H₂S generation by β-replacement of cysteine by homocysteine. The alternative H₂S-generating reactions, i.e. β-elimination of cysteine to generate serine or condensation of 2 mol of cysteine to generate lanthionine, are quantitatively less significant. The kinetic data were employed to simulate the turnover numbers of the various CBS-catalyzed reactions at physiologically relevant substrate concentrations. At equimolar concentrations of CBS and CSE, the simulations predict that H₂S production by CBS would account for ∼25–70% of the total H₂S generated via the trans-sulfuration pathway depending on the extent of allosteric activation of CBS by S-adenosylmethionine. The relative contribution of CBS to H₂S genesis is expected to decrease under hyperhomocysteinemic conditions. CBS is predicted to be virtually the sole source of lanthionine, and CSE, but not CBS, efficiently cleaves lanthionine. The insensitivity of the CBS-catalyzed H₂S-generating reactions to the grade of hyperhomocysteinemia is in stark contrast to the responsiveness of CSE and suggests a previously unrecognized role for CSE in intracellular homocysteine management. Finally, our studies reveal that the profligacy of the trans-sulfuration pathway results not only in a multiplicity of H₂S-yielding reactions but also yields novel thioether metabolites, thus increasing the complexity of the sulfur metabolome.Hydrogen sulfide (H₂S)² elicits an array of physiological effects, including modulation of blood pressure and reduction of ischemia reperfusion injury (1, 2). Other novel effects of H₂S include induction of a state of suspended animation in mouse by decreasing oxygen consumption and drastically reducing the metabolic rate (3) and synchronizing ultradian metabolic oscillation in yeast (4). Under conditions of metabolic cycling in yeast, H₂S production is catalyzed by sulfite reductase in the sulfur assimilation pathway (4). Inhibition of sulfite reductase reduces H₂S production and in turn perturbs metabolic oscillations. H₂S is a specific and potent inhibitor of cytochrome c oxidase in the electron transport chain (3).Although concentrations of H₂S have been reported to range from 50 to 160 μm in brain (5–7) and 30–50 μm in the peripheral system (8), these appear to be grossly overestimated (9). Significantly lower H₂S concentrations of 17 and 14 nm in liver and brain, respectively, have been reported recently (9). The very significant discrepancy between these and the previous estimates of H₂S levels presumably derives from the earlier use of acidic conditions that led to the release of acid-labile sulfur from iron-sulfur centers.In mammals, the primary catalysts for H₂S generation are reported to be the two pyridoxal phosphate (PLP)-dependent enzymes involved in the trans-sulfuration pathway, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) (10, 11). The trans-sulfuration pathway operates in the reverse direction in mammals serving to convert homocysteine to cysteine (Fig. 1), although in yeast and bacteria the pathway is involved in sulfur assimilation from sulfate to cysteine. CBS is widely assumed to be the major contributor to H₂S production in the brain because of its relatively high expression in this organ (10). However, a recent study reported that 3-mercaptopyruvate sulfurtransferase together with cysteine aminotransferase might also generate H₂S in brain (12). The relative contributions of these enzymes and of CSE, which is also present in brain (13, 14), to H₂S production remain to be assessed. Genetic disruption of CSE in mouse leads to cardiac deficits, including pronounced hypertension and reduced endothelium-dependent vasorelaxation, consistent with a major role for CSE in the peripheral system (1). However, brain H₂S levels are reportedly unchanged in CSE^−/− mice.Open in a separate windowFIGURE 1.Diversity of reactions catalyzed by the trans-sulfuration pathway. The turnover numbers (v/[E]) estimated at physiological substrate concentrations, i.e. 10 μm homocysteine, 100 μm cysteine, 560 μm serine, and 5 μm cystathionine, are shown in parentheses for each reaction. The thick arrows highlight reactions that are sensitive to elevated levels of homocysteine. The fold change represents the fold increase in the turnover number of a given reaction under conditions of severe hyperhomocysteinemia (200 μm homocysteine).Despite the growing recognition of the varied physiological effects of H₂S, our understanding of its regulation and mechanism of its biosynthesis is poor. We have recently reported on the complex kinetics of H₂S generation by human CSE (15). The profligacy of the human enzyme affords H₂S generation by a multiplicity of routes involving cysteine and/or homocysteine as substrates. Kinetic simulations predict an increasingly important contribution of homocysteine to H₂S generation with increasing grade of hyperhomocysteinemia, a risk factor for cardiovascular and neurodegenerative diseases (16–18). In addition to H₂S, a variety of products is generated in these reactions, including two novel sulfur metabolites, lanthionine and homolanthionine, which represent the condensation products between 2 mol of cysteine and homocysteine, respectively. Although the steady-state kinetic parameters for H₂S generation from cysteine and homocysteine have been reported for human CBS (hCBS) (19), a comparable detailed kinetic analysis of H₂S generation by CBS by multiple pathways and their sensitivity to the grade of hyperhomocysteinemia is not known. Furthermore, the relative contributions of CBS and CSE to H₂S and lanthionine generation at physiologically relevant concentrations of substrate are not known.Human CBS is a unique heme containing PLP-dependent enzyme (20) that catalyzes the β-replacement of serine by homocysteine to produce cystathionine. The latter is further metabolized by CSE in an α,γ-elimination reaction to produce cysteine. Although yeast and human CBS are highly homologous and catalyze the same chemical reaction with similar kinetic parameters, the yeast enzyme lacks heme and is not allosterically regulated by S-adenosylmethionine (AdoMet) (21).In this study, we have elucidated the kinetics of H₂S biogenesis by yeast and human CBS and used simulations to estimate the relative contributions of CBS and CSE to H₂S production at physiologically relevant concentrations of substrate. We find that CBS and CSE share a common feature, i.e. catalytic promiscuity. However, in contrast to CSE, which is proficient at catalyzing reactions at the β- and γ-carbons of substrates (15), CBS activity is confined to chemical transformations at the β-position. Our studies provide new insights into the existence of alternative trans-sulfuration reactions that can be a source of diverse sulfur metabolites, viz. H₂S, lanthionine, and homolanthionine increasing the diversity of the sulfur metabolome.     

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.