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991.
Background
Host-microbe and microbe-microbe interactions are often governed by the complex exchange of metabolites. Such interactions play a key role in determining the way pathogenic and commensal species impact their host and in the assembly of complex microbial communities. Recently, several studies have demonstrated how such interactions are reflected in the organization of the metabolic networks of the interacting species, and introduced various graph theory-based methods to predict host-microbe and microbe-microbe interactions directly from network topology. Using these methods, such studies have revealed evolutionary and ecological processes that shape species interactions and community assembly, highlighting the potential of this reverse-ecology research paradigm.Results
NetCooperate is a web-based tool and a software package for determining host-microbe and microbe-microbe cooperative potential. It specifically calculates two previously developed and validated metrics for species interaction: the Biosynthetic Support Score which quantifies the ability of a host species to supply the nutritional requirements of a parasitic or a commensal species, and the Metabolic Complementarity Index which quantifies the complementarity of a pair of microbial organisms’ niches. NetCooperate takes as input a pair of metabolic networks, and returns the pairwise metrics as well as a list of potential syntrophic metabolic compounds.Conclusions
The Biosynthetic Support Score and Metabolic Complementarity Index provide insight into host-microbe and microbe-microbe metabolic interactions. NetCooperate determines these interaction indices from metabolic network topology, and can be used for small- or large-scale analyses. NetCooperate is provided as both a web-based tool and an open-source Python module; both are freely available online at http://elbo.gs.washington.edu/software_netcooperate.html. 相似文献992.
Wnt4 action in gonadal development and sex determination 总被引:1,自引:0,他引:1
Wnt4 is a growth factor involved in multiple developmental processes such as the formation of the kidney, adrenal, mammary gland, pituitary and the female reproductive system. During mammalian embryogenesis, Wnt4 is expressed in the gonads of both sexes before sex determination events take place and is subsequently down-regulated in the male gonad. Inactivation of the Wnt4 gene in mice has revealed that it is involved at several steps of female reproductive development. Wnt4 is implicated in Müllerian duct regression, the formation of sex-specific vasculature, the inhibition of steroidogenesis and in sex-specific cell migration events. A mouse model of sex-reversal has partially unravelled the molecular pathways in which Wnt4 operates during the development of the female reproductive system. However, the specific molecular mechanism of action of Wnt4 during gonadal development remains unknown. This and downstream signaling pathways involved in Wnt4 action during female gonad development are reviewed and models of Wnt4 action are proposed for Müllerian duct formation, sex-specific vasculature development, and sex determination events. Further identification of critical downstream effectors of the Wnt4 signaling pathway in mouse models and in patients with sex-reversal conditions could help in understanding sex-reversal pathologies in humans. 相似文献
993.
Harris M Firsov D Vuagniaux G Stutts MJ Rossier BC 《The Journal of biological chemistry》2007,282(1):58-64
The amiloride-sensitive epithelial sodium channel (ENaC) constitutes a limiting step in sodium reabsorption across distal airway epithelium and controlling mucociliary clearance. ENaC is activated by serine proteases secreted in the extracellular milieu. In cystic fibrosis lungs, high concentrations of secreted neutrophil elastase (NE) are observed. hNE could activate ENaC and contribute to further decreased mucociliary clearance. The aims of this study were (i) to test the ability of an engineered human neutrophil elastase inhibitor (EPI-hNE4) to specifically inhibit the elastase activation of ENaC-mediated amiloride-sensitive currents (I(Na)) and (ii) to examine the effect of elastase on cell surface expression of ENaC and its cleavage pattern (exogenous proteolysis). Oocytes were exposed to hNE (10-100 microg/ml) and/or trypsin (10 microg/ml) for 2-5 min in the presence or absence of EPI-hNE4 (0.7 microm). hNE activated I(Na) 3.6-fold (p < 0.001) relative to non-treated hENaC-injected oocytes. EPI-hNE4 fully inhibited hNE-activated I(Na) but had no effect on trypsin- or prostasin-activated I(Na). The co-activation of I(Na) by hNE and trypsin was not additive. Biotinylation experiments revealed that cell surface gamma ENaC (but not alpha or beta ENaC) exposed to hNE for 2 min was cleaved (as a 67-kDa fragment) and correlated with increased I(Na). The elastase-induced exogenous proteolysis pattern is distinct from the endogenous proteolysis pattern induced upon preferential assembly, suggesting a causal relationship between gamma ENaC cleavage and ENaC activation, taking place at the plasma membrane. 相似文献
994.
A FRET analysis to unravel the role of cholesterol in Rac1 and PI 3-kinase activation in the InlB/Met signalling pathway 总被引:1,自引:0,他引:1
The signalling pathway for the hepatocyte growth factor receptor, Met/HGF-R, is hijacked by the bacterial surface protein InlB to induce Listeria monocytogenes entry into non-phagocytic cells. We previously showed that Listeria invades host cells by interacting with specialized microdomains of the host plasma membrane called lipid rafts. In this study, we analysed in living cells signalling events that are crucial for Listeria entry using a fluorescence resonance energy transfer-based microscopic method. Phosphoinositide (PI) 3-kinase activity and Rac1 signalling induced by Listeria interacting with epithelial cells were monitored as well as signalling induced by soluble InlB and the Met natural ligand HGF. We found that InlB and HGF induced similar kinetics of PI 3-kinase and Rac1 activation. PI 3-kinase activation was upstream and independent of Rac1 activation. Cholesterol-depletion experiments were performed to address the role of lipid rafts in Met signalling. The amount of 3'-phosphoinositides produced by PI 3-kinase was not affected by cholesterol depletion, while their membrane dynamic was cholesterol-dependent. Rac1 activation, downstream from PI 3-kinase, was cholesterol-dependent suggesting that the spatial distribution of 3'-phosphoinositides within membrane microdomains is critical for Rac1 activation and consequently for F-actin assembly at bacterial entry site. 相似文献
995.
Stewart BW 《Mutation research》2008,658(1-2):124-151
Readily achieved comparative assessment of carcinogenic risks consequent upon environmental exposures may increase understanding and contribute to cancer prevention. Procedures for hazard identification and quantitative risk assessment are established, but limited when addressing novel exposures to previously known carcinogens or any exposure to agents having only suspected carcinogenic activity. To complement other means of data evaluation, a procedure for qualitative assessment of carcinogenic risk is described. This involves categorizing the relevant carcinogen and circumstances under which exposure occurs. The categories for carcinogens are those used for hazard identification and involve whether the agent is (1) a recognized carcinogen for humans; (2) probably or (3) possibly carcinogenic for humans; (4) characterized by inadequate evidence of carcinogenicity; or (5) lacking carcinogenicity. Exposure is categorized by whether it is one which (1) establishes the agent as a recognized carcinogen; (2) is taken into account in establishing carcinogenicity status; (3) is distinct from those providing clearest evidence of carcinogenicity; (4) is not characterized in relation to carcinogenicity; or (5) involves an exposure in which absence of carcinogenic outcome is observed. These two categories of evidence allow the risk inherent in a situation to be banded as indicative of a proven, likely, inferred, unknown or unlikely carcinogenic outcome, and further characterized using sub-bands. The procedure has been applied to about fifty situations. For recognized carcinogens, including asbestos and polycyclic aromatic hydrocarbons, risks consequent upon occupational exposure, the impact of point source pollution, residence near contaminated sites and general environmental exposure are allocated across the proven band and a likely sub-band. For solvents, pesticides and other compounds having less clearly established carcinogenicity, impact on residents living near a production site, or near earlier related industrial activity is allocated to certain inferred sub-bands. Unknown carcinogenic outcome, which identifies exposure to an agent with inadequate evidence of carcinogenicity rather than being indicative of equivocal or negative data in any context, indicates both the impact of certain pollutants and user-exposure to some consumer products. Situations allocated to the unlikely risk band principally involve certain consumer products. Overall, such risk assessment may be of greatest worth in focusing community attention on proven causes of cancer and associated preventive measures. 相似文献
996.
Moretto A Formaggio F Kaptein B Broxterman QB Wu L Keiderling TA Toniolo C 《Biopolymers》2008,90(4):567-574
The difference in length between the more elongated peptide 3(10)-helix and the more compact alpha-helix is about 0.4 A/residue. This property makes the 3(10)-/alpha-helix reversible conversion very promising as a molecular switching tool between the N- and C-terminal functions of a peptide backbone. In this work, using homo-peptides of various main-chain length, all based on the strongly helicogenic, Calpha-tetrasubstituted alpha-amino acid Calpha-methyl-L-valine, we show that a well defined, solvent controlled, reversible 3(10)-/alpha-helix transition takes place even in a homo-oligomer as short as a terminally blocked hexapeptide. Homo-peptide sequences blocked as a urethane or an acetamide at the N-terminus and as a methyl ester or an N-alkyl amide at the C-terminus are all appropriate. The nature of the occurring helical species in the various solvents tested was assessed by electronic or vibrational circular dichroism. 相似文献
997.
Jason S. Link Bernard A. Megrey Thomas J. Miller Tim Essington Jennifer Boldt Alida Bundy Erlend Moksness Ken F. Drinkwater R. Ian Perry 《Biology letters》2010,6(6):723-726
Understanding the drivers that dictate the productivity of marine ecosystems continues to be a globally important issue. A vast literature identifies three main processes that regulate the production dynamics of such ecosystems: biophysical, exploitative and trophodynamic. Exploring the prominence among this ‘triad’ of drivers, through a synthetic analysis, is critical for understanding how marine ecosystems function and subsequently produce fisheries resources of interest to humans. To explore this topic further, an international workshop was held on 10–14 May 2010, at the National Academy of Science''s Jonsson Center in Woods Hole, MA, USA. The workshop compiled the data required to develop production models at different hierarchical levels (e.g. species, guild, ecosystem) for many of the major Northern Hemisphere marine ecosystems that have supported notable fisheries. Analyses focused on comparable total system biomass production, functionally equivalent species production, or simulation studies for 11 different marine fishery ecosystems. Workshop activities also led to new analytical tools. Preliminary results suggested common patterns driving overall fisheries production in these ecosystems, but also highlighted variation in the relative importance of each among ecosystems. 相似文献
998.
Wilson R. Lourenço Bernard Duhem John L. Cloudsley-Thompson 《Comptes rendus biologies》2010,333(3):280-285
A new genus and species of peri-Saharian buthid scorpion is described on the basis of single specimen collected in the Great Rift Valley, North of Kenya. This new scorpion taxon represents yet another endemic relict element for the faunas of the peri-Saharian regions. Comments are also included on the evolution of the Sahara and peri-Saharian regions and its possible consequences on the distribution of the extant scorpion fauna. 相似文献
999.
Validation of Horne and Ostberg morningness-eveningness questionnaire in a middle-aged population of French workers 总被引:3,自引:0,他引:3
As suggested by the authors, the Horne and Ostberg morning/evening questionnaire (MEQ) has never been adapted to evaluate a nonstudent population. The purpose of this study was to validate this MEQ in a sample of middle-aged workers by modifying only the cutoffs. It was administered in 566 non-shift-workers aged 51.2 to 3.2 years who presented no sleep disorders. According to the Home and Ostberg classification, the sample consisted of 62.1% morning type, 36.6% neither type, and 2.2% evening type. Multiple correspondence analysis, which determines the principal components, was performed on all MEQ items. Then an ascending hierarchical classification was applied to determine 3 clusters from these principal components. On the basis of these 3 clusters, new cutoffs were determined: evening types were considered as scoring under 53 and morning types above 64, thus giving 28.1% morning type, 51.7% neither type, and 20.2% evening type. As an external validation, eveningness was associated with later bedtime and waking-up time (more pronounced at the weekend), greater need for sleep, larger daily sleep debt, greater morning sleepiness, and ease of returning to sleep in the early morning. A positive correlation between age and morningness was again found. This study confirms that "owls" are not rare in a middle-aged sample. We conclude that this adapted MEQ could be useful when investigating age-related changes in sleep. 相似文献
1000.
Aziz Sheikh Laila Halani Raj Bhopal Gopalakrishnan Netuveli Martyn R. Partridge Josip Car Chris Griffiths Mark Levy 《PLoS medicine》2009,6(10)