Human hippocampal astrocytes: Computational dissection of their transcriptome, sexual differences and exosomes across ageing and mild-cognitive impairment.

The role of astrocytes in Alzheimer's disease is often disregarded. Hence, characterization of astrocytes along their early evolution toward Alzheimer would be greatly beneficial. However, due to their exquisite responsiveness, in vivo studies are difficult.

Mapping the transcriptomic changes of endothelial compartment in human hippocampus across aging and mild cognitive impairment.

Compromise of the vascular system has important consequences on cognitive abilities and neurodegeneration. The identification of the main molecular signatures present in the blood vessels of human hippocampus could provide the basis to understand and tackle these pathologies. As direct vascular experimentation in hippocampus is problematic, we achieved this information by computationally disaggregating publicly available whole microarrays data of human hippocampal homogenates.

Influence of Glucose Availability and CRP Acetylation on the Genome-Wide Transcriptional Response of : Assessment by an Optimized Factorial Microarray Analysis.

While in eukaryotes acetylation/deacetylation regulation exerts multiple pleiotropic effects, in it seems to be more limited and less known. Hence, we aimed to progress in the characterization of this regulation by dealing with three convergent aspects: the effector enzymes involved, the master regulator CRP, and the dependence on glucose availability. The transcriptional response of BW25113 was analyzed across 14 relevant scenarios.

Sexual Dimorphism and Aging in the Human Hyppocampus: Identification, Validation, and Impact of Differentially Expressed Genes by Factorial Microarray and Network Analysis.

In the brain of elderly-healthy individuals, the effects of sexual dimorphism and those due to normal aging appear overlapped. Discrimination of these two dimensions would powerfully contribute to a better understanding of the etiology of some neurodegenerative diseases, such as "sporadic" Alzheimer. Following a system biology approach, top-down and bottom-up strategies were combined.

Q-GDEMAR: a general method for the identification of differentially expressed genes in microarrays with unbalanced groups.

Microarray analysis is a powerful tool to simultaneously determine the pattern of transcription of large amounts of genes. For data post-processing distinct computational methods are currently used that, however, lead to different results regarding the genes expressed differentially. Herein, a new methodology for microarray data analysis named Q-GDEMAR is presented.

Analysis of cell adhesion during early stages of colon cancer based on an extended multi-valued logic approach.

Cell adhesion in the normal colon is typically associated with differentiated cells, whereas in cancerous colon it is associated with advanced tumors. For advanced tumors growing evidence supports the existence of stem-like cells that have originated from transdifferentiation. Because stem cells can also be transformed in their own niche, at the base of the Lieberkühn's crypts, we conjectured that cell adhesion can also be critical in early tumorigenesis.

Model identification in presence of incomplete information by generalized principal component analysis: application to the common and differential responses of Escherichia coli to multiple pulse perturbations in continuous, high-biomass density culture.

In a previous report we described a multivariate approach to discriminate between the different response mechanisms operating in Escherichia coli when a steady, continuous culture of these bacteria was perturbed by a glycerol pulse (Guebel et al., 2009, Biotechnol Bioeng 102: 910-922). Herein, we present a procedure to extend this analysis when multiple, spaced pulse perturbations (glycerol, fumarate, acetate, crotonobetaine, hypersaline plus high-glycerol basal medium and crotonobetaine plus hypersaline basal medium) are being assessed.

Analysis of the Escherichia coli response to glycerol pulse in continuous, high-cell density culture using a multivariate approach.

Pulse experiments in continuous-culture are a valuable tool in microbial physiology research. However, inferences become difficult when the cell response is followed by monitoring many biochemical variables or when several types of perturbations are compared. Moreover, there is no objective criterion to delimit the time-window, so that the recorded responses will render valid inferences.

A computer model of oxygen dynamics in human colon mucosa: implications in normal physiology and early tumor development.

Based on the geometry of the colon mucosa, we built a model to compute the oxygen supply, the oxygen diffusion across the interstitial matrix, and the oxygen consumption by cryptal and stromal cells. By using an iterative algorithm, we have been able to solve a set of discretized (time and space) oxygen balance equations and determine the three-dimensional distribution of pO(2) in the mucosa. Although significant longitudinal and radial pO(2) variations were found, cells appeared to operate at their maximum respiratory capacity, regardless of their location in the tissue.

Dynamics of sulfur amino acids in mammalian brain: assessment of the astrocytic-neuronal cysteine interaction by a mathematical hybrid model.

A mathematically hybrid model was used to analyze three mechanisms by which cysteine could be produced in the brain to be used as preferential substrate in the synthesis of neuronal glutathione. In that way, the fluxes of sulfur-compounds at the brain-blood barrier were integrated with their transport in astrocytes and neurons, and with their metabolism in astrocytes. We concluded that cysteine, in contrast with its precursor cystine, would not be taken up from the blood at the blood-brain barrier, but instead it must be lost continuously from astrocytes.

Canonical sensitivities: a useful tool to deal with large perturbations in metabolic network modeling.

The dynamic range of metabolic models can be extended to deal with large perturbations by introducing the related concepts of "generalized" kinetic order and "canonical" sensitivities. Generalized kinetic orders are built as a well-defined non linear combination of the canonical sensitivities coefficients, which in turn are obtained by a least-squares regression on central composite factorial design data. In a such way, the whole domain of the operating variables is mapped without need to determine locally neither the first nor the second order model derivatives.