A functional metabolic map of Faecalibacterium prausnitzii, a beneficial human gut microbe

in Journal of Bacteriology (2014), 196(18), 3289-3302

The human gut microbiota plays a central role in human well-being and disease. In this study, we present an integrated, iterative approach of computational modeling, in vitro experiments, metabolomics ... [more ▼]

The human gut microbiota plays a central role in human well-being and disease. In this study, we present an integrated, iterative approach of computational modeling, in vitro experiments, metabolomics, and genomic analysis to accelerate the identification of metabolic capabilities for poorly characterized (anaerobic) microorganisms. We demonstrate this approach for the beneficial human gut microbe Faecalibacterium prausnitzii strain A2-165. We generated an automated draft reconstruction, which we curated against the limited biochemical data. This reconstruction modeling was used to develop in silico and in vitro a chemically defined medium (CDM), which was validated experimentally. Subsequent metabolomic analysis of the spent medium for growth on CDM was performed. We refined our metabolic reconstruction according to in vitro observed metabolite consumption and secretion and propose improvements to the current genome annotation of F. prausnitzii A2-165. We then used the reconstruction to systematically characterize its metabolic properties. Novel carbon source utilization capabilities and inabilities were predicted based on metabolic modeling and validated experimentally. This study resulted in a functional metabolic map of F. prausnitzii, which is available for further applications. The presented workflow can be readily extended to other poorly characterized and uncharacterized organisms to yield novel biochemical insights about the target organism. [less ▲]

Functional nano fillers in epoxy-dicyandiamide adhesives for prolonged shelf life and efficient cure

in e-Polymers (2011), (10), 1-15

Shelf life at room temperature and curing behaviour at elevated temperature are studied for hot-curing accelerated epoxies (EP, diglycidylether of bisphenol A plus dicyandiamide (Dicy)) by FTIR ... [more ▼]

Shelf life at room temperature and curing behaviour at elevated temperature are studied for hot-curing accelerated epoxies (EP, diglycidylether of bisphenol A plus dicyandiamide (Dicy)) by FTIR-spectroscopy and modulated DSC. The accelerator is added either directly or with nano-zeolite filler to the EP. Due to the immobilization of the accelerator in the pores of the nano-zeolite, the shelf life of this EP is 5 times longer than for the EP containing free accelerator. While the free accelerator acts during the whole heating step to curing temperature, the nano-zeolite does not release the accelerator before ca. 100 °C. As monitored by light microscopy, the released accelerator not only supports the curing but also stimulates the dissolution of the solid Dicy. As the result, network formation at 170 °C finishes within less than 25 minutes for the nano-filled EP. [less ▲]

Functional organization of the yeast proteome by systematic analysis of protein complexes.

in Nature (2002), 415(6868), 141-7

Most cellular processes are carried out by multiprotein complexes. The identification and analysis of their components provides insight into how the ensemble of expressed proteins (proteome) is organized ... [more ▼]

Most cellular processes are carried out by multiprotein complexes. The identification and analysis of their components provides insight into how the ensemble of expressed proteins (proteome) is organized into functional units. We used tandem-affinity purification (TAP) and mass spectrometry in a large-scale approach to characterize multiprotein complexes in Saccharomyces cerevisiae. We processed 1,739 genes, including 1,143 human orthologues of relevance to human biology, and purified 589 protein assemblies. Bioinformatic analysis of these assemblies defined 232 distinct multiprotein complexes and proposed new cellular roles for 344 proteins, including 231 proteins with no previous functional annotation. Comparison of yeast and human complexes showed that conservation across species extends from single proteins to their molecular environment. Our analysis provides an outline of the eukaryotic proteome as a network of protein complexes at a level of organization beyond binary interactions. This higher-order map contains fundamental biological information and offers the context for a more reasoned and informed approach to drug discovery. [less ▲]

Functional relevance of ceruloplasmin mutations in Parkinson's disease.

in FASEB journal : official publication of the Federation of American Societies for Experimental Biology (2005), 19(13), 1851-3

Increased iron levels of the substantia nigra and the discovery of ceruloplasmin mutations in patients with Parkinson's disease (PD) imply impaired iron metabolism in this neurodegenerative disorder ... [more ▼]

Increased iron levels of the substantia nigra and the discovery of ceruloplasmin mutations in patients with Parkinson's disease (PD) imply impaired iron metabolism in this neurodegenerative disorder. Ceruloplasmin has ferroxidase activity oxidizing iron(II) to iron(III). In the present study, we analyzed the amount of ceruloplasmin, iron, ferritin, and transferrin and the ceruloplasmin ferroxidase activity in serum of patients with the diagnosis of PD carrying the ceruloplasmin mutations I63T, D544E, and R793H. The impact of these missense mutations on the biosynthesis of holo-ceruloplasmin was investigated in cell culture experiments. Functional relevance was found for the ceruloplasmin mutations I63T and D544E. In vivo, the I63T mutation resulted in half the normal ceruloplasmin concentration and markedly reduced ferroxidase activity in serum from a heteroallelic PD patient. In cell culture, the I63T glycosylphosphatidylinositol (GPI)-linked ceruloplasmin isoform was retained in the endoplasmatic reticulum of human embryonic kidney cells. Furthermore, the D544E polymorphism resulted in significantly reduced serum ceruloplasmin levels and ferroxidase activity in heteroallelic patients and in expression of mainly apo-ceruloplasmin in cell culture. Our studies indicate that altered activity of ceruloplasmin may present a vulnerability factor for iron induced oxidative stress in PD. [less ▲]

The functionally defined right occipital and fusiform "face areas" discriminate novel from visually familiar faces

in NeuroImage (2003), 19(3), 877-883

Neuroimaging (PET and fMRI) studies have identified a set of brain areas responding more to faces than to other object categories in the visual extrastriate cortex of humans. This network includes the ... [more ▼]

Neuroimaging (PET and fMRI) studies have identified a set of brain areas responding more to faces than to other object categories in the visual extrastriate cortex of humans. This network includes the middle lateral fusiform gyrus (the fusiform face area, or FFA) as well as the inferior occipital gyrus (occipital face area, OFA). The exact functions of these areas in face processing remain unclear although it has been argued that their primary function is to distinguish faces from nonface object categories-"face detection"-or also to discriminate among faces, irrespective of their visual familiarity to the observer. Here, we combined the data from two previous positron emission tomography (PET) studies to show that the functionally defined face areas are involved in the automatic discrimination between unfamiliar faces and familiar faces. Consistent with previous studies, a face localizer contrast (faces-objects) revealed bilateral activation in the middle lateral fusiform gyrus (FFA, BA37) and in the right inferior occipital cortex (OFA, BA19). Within all the regions of the right hemisphere, larger levels of activation were found for unfamiliar as compared to familiar faces. These results suggest that the very same areas involved in categorizing faces at the basic or individual level, play a role in differentiating familiar faces from new faces, showing an overlap between visual and presemantic mnesic representations of faces in the right hemisphere. [less ▲]

Functions on Probabilistic Graphical Models

in Proceedings of the International Multiconference on Computer Science and Information Technology IMCSIT 2009 (2009)

The fund Synthetic Index : An alternative benchmark for mutual funds

in Bankers, Markets, Investors [=BMI] (2011), 114

Evaluation of the performance of investment funds is a topic of considerable interest to practitioners and academic researchers. Performance indicators of fi nancial places have for long posed interesting ... [more ▼]

Evaluation of the performance of investment funds is a topic of considerable interest to practitioners and academic researchers. Performance indicators of fi nancial places have for long posed interesting challenges with regards to funds investors, but also to legal regulators authorities. The two major issues that need to be addressed in any performance study are how to choose an appropriate benchmark for comparison and how to adjust a fund’s return for risk. Indeed, investors desire information about representative market indexes as a norm to evaluate the performance of their portfolios. MSCI Indexes are frequently used by institutional investors around the world as benchmarks to decide allocation of funds across asset classes and regions. Despite this wide acceptance, MSCI country index has in its original application a number of drawbacks and limitations. The main problems can be traced to the presence of usual biases, such as sampling, survivorship and instant history biases (Fung and Shieh, 2002), involving problems into the aggregation procedure. Thus, one can explain why certain fi nancial places are less representative, specifi cally for funds distribution places. Some results also indicate problems related to misclassifi cation in mutual funds (Sharpe, 1992). Each of these phenomena can have a signifi cant impact on international diversifi cation for fund managers. Based on these empirical fi ndings, Ferreira, Miguel and Ramos (2007) examine cross-country mutual fund performance using several alternative benchmark models including a domestic and an international version of the Carhart (1997) four-factor model. Using multiple regressions, they obtain signifi cant determinants explaining funds performance, like the funds size, the fees, the management style… . In this article, we contribute to the existing discussion on alternative benchmarks to compare fi nancial places, by conducting an analysis on funds time variation structure. Contrary to previous literature, we propose to use directly the information contained in the NAV to extract performance characteristics of funds. Then, each domiciliation place is compared by constructing a fund synthetic index that will capture the time structure of mutual fund performance. Usual statistical approach consists to estimate fi nancial returns of each fund in each country, which involves dealing with huge data sets that may cause the calculation processes to become slow and cumbersome and the results diffi cult to be interpreted and used in further applications. To reduce data sets, and give conclusions for each fi nancial place, indicators of the mean of fund’s returns can be used. Then one can identify classes of domicile funds that are subject to common properties. But this classical approach, gives only approximate results because it is based on an aggregation of average performance and risk and a boxplot statistical format. The construction of fund synthetic portfolio avoids this issue. First, it avoids the logic of representativity through market capitalization that is often diffi cult to apply to the mutual fund universe. Second, it is based on factor analysis techniques to generate indexes that are able to capture a very large fraction of the information. More precisely, it permits to take into account the common properties of fund returns relative to their domicile while keeping the maximum of information given by the original data. Indeed, it may be very useful to use a transformation to form a simplifi ed data set retaining the characteristics of the original data set. Principal component analysis, abbreviated as PCA, is a method of statistical analysis useful in data reduction and interpretation of multivariate data sets by identifying factors of common behavior such that not much of the contained information is lost. In our context, we use this method to derive portfolio weights in order to construct a synthetic portfolio of each fi nancial place. For that, we propose to replace the matrix of returns and to derive an index which keeps the global representation of each fi nancial place. [less ▲]

Fundamental limits to helical edge conductivity due to sphin-phonon scattering

in Physical Review. B, Condensed Matter (2018), 97

Fundamental Rights Agency Annual Report (2011): European Law in the field of asylum, immigration and integration

Report (2011)

Fundamental Rights of People with Intellectual Disabilities and People with Mental Health Problems

Report (2011)