Metabolomics approach for determining growth-specific metabolites based on Fourier transform ion cyclotron resonance mass spectrometry

Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR/MS) is the best MS technology for obtaining exact mass measurements owing to its great resolution and accuracy, and several outstanding FT-ICR/MS-based metabolomics approaches have been reported. A reliable annotation scheme is needed to deal with direct-infusion FT-ICR/MS metabolic profiling. Correlation analyses can help us not only uncover relations between the ions but also annotate the ions originated from identical metabolites (metabolite derivative ions). In the present study, we propose a procedure for metabolite annotation on direct-infusion FT-ICR/MS by taking into consideration the classification of metabolite-derived ions using correlation analyses. Integrated analysis based on information of isotope relations, fragmentation patterns by MS/MS analysis, co-occurring metabolites, and database searches (KNApSAcK and KEGG) can make it possible to annotate ions as metabolites and estimate cellular conditions based on metabolite composition. A total of 220 detected ions were classified into 174 metabolite derivative groups and 72 ions were assigned to candidate metabolites in the present work. Finally, metabolic profiling has been able to distinguish between the growth stages with the aid of PCA. The constructed model using PLS regression for OD600 values as a function of metabolic profiles is very useful for identifying to what degree the ions contribute to the growth stages. Ten phospholipids which largely influence the constructed model are highly abundant in the cells. Our analyses reveal that global modification of those phospholipids occurs as E. coli enters the stationary phase. Thus, the integrated approach involving correlation analyses, metabolic profiling, and database searching is efficient for high-throughput metabolomics

Differential information in large games with strategic complementarities

We study equilibrium in large games of strategic complementarities (GSC) with differential information. We define an appropriate notion of distributional Bayesian Nash equilibrium and prove its existence. Furthermore, we characterize order-theoretic properties of the equilibrium set, provide monotone comparative statics for ordered perturbations of the space of games, and provide explicit algorithms for computing extremal equilibria. We complement the paper with new results on the existence of Bayesian Nash equilibrium in the sense of Balder and Rustichini (J Econ Theory 62(2):385–393, 1994) or Kim and Yannelis (J Econ Theory 77(2):330–353, 1997) for large GSC and provide an analogous characterization of the equilibrium set as in the case of distributional Bayesian Nash equilibrium. Finally, we apply our results to riot games, beauty contests, and common value auctions. In all cases, standard existence and comparative statics tools in the theory of supermodular games for finite numbers of agents do not apply in general, and new constructions are required

Unique Flexibility in Energy Metabolism Allows Mycobacteria to Combat Starvation and Hypoxia

Mycobacteria are a group of obligate aerobes that require oxygen for growth, but paradoxically have the ability to survive and metabolize under hypoxia. The mechanisms responsible for this metabolic plasticity are unknown. Here, we report on the adaptation of Mycobacterium smegmatis to slow growth rate and hypoxia using carbon-limited continuous culture. When M. smegmatis is switched from a 4.6 h to a 69 h doubling time at a constant oxygen saturation of 50%, the cells respond through the down regulation of respiratory chain components and the F1Fo-ATP synthase, consistent with the cells lower demand for energy at a reduced growth rate. This was paralleled by an up regulation of molecular machinery that allowed more efficient energy generation (i.e. Complex I) and the use of alternative electron donors (e.g. hydrogenases and primary dehydrogenases) to maintain the flow of reducing equivalents to the electron transport chain during conditions of severe energy limitation. A hydrogenase mutant showed a 40% reduction in growth yield highlighting the importance of this enzyme in adaptation to low energy supply. Slow growing cells at 50% oxygen saturation subjected to hypoxia (0.6% oxygen saturation) responded by switching on oxygen scavenging cytochrome bd, proton-translocating cytochrome bc1-aa3 supercomplex, another putative hydrogenase, and by substituting NAD+-dependent enzymes with ferredoxin-dependent enzymes thus highlighting a new pattern of mycobacterial adaptation to hypoxia. The expression of ferredoxins and a hydrogenase provides a potential conduit for disposing of and transferring electrons in the absence of exogenous electron acceptors. The use of ferredoxin-dependent enzymes would allow the cell to maintain a high carbon flux through its central carbon metabolism independent of the NAD+/NADH ratio. These data demonstrate the remarkable metabolic plasticity of the mycobacterial cell and provide a new framework for understanding their ability to survive under low energy conditions and hypoxia

Host Cell Transcriptome Profile during Wild-Type and Attenuated Dengue Virus Infection

10.1371/journal.pntd.0002107PLoS Neglected Tropical Diseases73

Older Adults’ Participation in VIAS’ Mobile App Design

The literature is consensual when it tells us that the choice of the intergenerational approach brings significant advantages, both for the youngest, the oldest and even for the technological products under development. Given this reality, this article describes some of the intergenerational workshops developed within the ViseuInterAgeStories Project (VIAS), although with a special focus on the participation of the elderly. VIAS promotes collaboration between children and the elderly in the creation of georeferenced stories in a mobile application while touring places of culture, heritage and a natural interest in the city of Viseu. To do so, they can publish local images, texts or audios or access stories already shared by other users, creating a city identity network. The project followed a Participatory Design approach, involving children and older adults during intergenerational dynamics and practices and to co-design the app. The results reveal the appreciation of the city’s history by the seniors and the importance of thematic categorization in the organization of the mobile application. Thus the App integrates georeferenced historical information. Even assuming difficulties in using the technology, participants built meaningful ideas of what they wanted and could get from it. Intergenerational experience and the co-design process have revealed positive implications for self-esteem and satisfaction among older people.info:eu-repo/semantics/publishedVersio