Sensing Gram-negative bacteria: a phylogenetic perspective.

Gram-negative bacteria represent a major group of pathogens that infect all eukaryotes from plants to mammals. Gram-negative microbe-associated molecular patterns include lipopolysaccharides and peptidoglycans, major immunostimulatory determinants across phyla. Recent advances have furthered our understanding of Gram-negative detection beyond the well-defined pattern recognition receptors such as TLR4. A B-type lectin receptor for LPS and Lysine-motif containing receptors for peptidoglycans were recently added to the plant arsenal. Caspases join the ranks of mammalian cytosolic immune detectors by binding LPS, and make TLR4 redundant for septic shock. Fascinating bacterial evasion mechanisms lure the host into tolerance or promote inter-bacterial competition. Our review aims to cover recent advances on bacterial messages and host decoding systems across phyla, and highlight evolutionarily recurrent strategies.

The EXS Domain of PHO1 Participates in the Response of Shoots to Phosphate Deficiency via a Root-to-Shoot Signal.

The response of shoots to phosphate (Pi) deficiency implicates long-distance communication between roots and shoots, but the participating components are poorly understood. We have studied the topology of the Arabidopsis (Arabidopsis thaliana) PHOSPHATE1 (PHO1) Pi exporter and defined the functions of its different domains in Pi homeostasis and signaling. The results indicate that the amino and carboxyl termini of PHO1 are both oriented toward the cytosol and that the protein spans the membrane twice in the EXS domain, resulting in a total of six transmembrane α-helices. Using transient expression in Nicotiana benthamiana leaf, we demonstrated that the EXS domain of PHO1 is essential for Pi export activity and proper localization to the Golgi and trans-Golgi network, although the EXS domain by itself cannot mediate Pi export. In contrast, removal of the amino-terminal hydrophilic SPX domain does not affect the Pi export capacity of the truncated PHO1 in N. benthamiana. While the Arabidopsis pho1 mutant has low shoot Pi and shows all the hallmarks associated with Pi deficiency, including poor shoot growth and overexpression of numerous Pi deficiency-responsive genes, expression of only the EXS domain of PHO1 in the roots of the pho1 mutant results in a remarkable improvement of shoot growth despite low shoot Pi. Transcriptomic analysis of pho1 expressing the EXS domain indicates an attenuation of the Pi signaling cascade and the up-regulation of genes involved in cell wall synthesis and the synthesis or response to several phytohormones in leaves as well as an altered expression of genes responsive to abscisic acid in roots.

Evidence for hypothalamic ketone body sensing: impact on food intake and peripheral metabolic responses in mice.

Monocarboxylates have been implicated in the control of energy homeostasis. Among them, the putative role of ketone bodies produced notably during high-fat diet (HFD) has not been thoroughly explored. In this study, we aimed to determine the impact of a specific rise in cerebral ketone bodies on food intake and energy homeostasis regulation. A carotid infusion of ketone bodies was performed on mice to stimulate sensitive brain areas for 6 or 12 h. At each time point, food intake and different markers of energy homeostasis were analyzed to reveal the consequences of cerebral increase in ketone body level detection. First, an increase in food intake appeared over a 12-h period of brain ketone body perfusion. This stimulated food intake was associated with an increased expression of the hypothalamic neuropeptides NPY and AgRP as well as phosphorylated AMPK and is due to ketone bodies sensed by the brain, as blood ketone body levels did not change at that time. In parallel, gluconeogenesis and insulin sensitivity were transiently altered. Indeed, a dysregulation of glucose production and insulin secretion was observed after 6 h of ketone body perfusion, which reversed to normal at 12 h of perfusion. Altogether, these results suggest that an increase in brain ketone body concentration leads to hyperphagia and a transient perturbation of peripheral metabolic homeostasis.

Semantic domain and grammatical class effects in the picture-word interference paradigm

The role of grammatical class in lexical access and representation is still not well understood. Grammatical effects obtained in picture-word interference experiments have been argued to show the operation of grammatical constraints during lexicalization when syntactic integration is required by the task. Alternative views hold that the ostensibly grammatical effects actually derive from the coincidence of semantic and grammatical differences between lexical candidates. We present three picture-word interference experiments conducted in Spanish. In the first two, the semantic relatedness (related or unrelated) and the grammatical class (nouns or verbs) of the target and the distracter were manipulated in an infinitive form action naming task in order to disentangle their contributions to verb lexical access. In the third experiment, a possible confound between grammatical class and semantic domain (objects or actions) was eliminated by using action-nouns as distracters. A condition in which participants were asked to name the action pictures using an inflected form of the verb was also included to explore whether the need of syntactic integration modulated the appearance of grammatical effects. Whereas action-words (nouns or verbs), but not object-nouns, produced longer reaction times irrespective of their grammatical class in the infinitive condition, only verbs slowed latencies in the inflected form condition. Our results suggest that speech production relies on the exclusion of candidate responses that do not fulfil task-pertinent criteria like membership in the appropriate semantic domain or grammatical class. Taken together, these findings are explained by a response-exclusion account of speech output. This and alternative hypotheses are discussed.

The serine protease hepsin mediates urinary secretion and polymerisation of Zona Pellucida domain protein uromodulin.

Uromodulin is the most abundant protein in the urine. It is exclusively produced by renal epithelial cells and it plays key roles in kidney function and disease. Uromodulin mainly exerts its function as an extracellular matrix whose assembly depends on a conserved, specific proteolytic cleavage leading to conformational activation of a Zona Pellucida (ZP) polymerisation domain. Through a comprehensive approach, including extensive characterisation of uromodulin processing in cellular models and in specific knock-out mice, we demonstrate that the membrane-bound serine protease hepsin is the enzyme responsible for the physiological cleavage of uromodulin. Our findings define a key aspect of uromodulin biology and identify the first in vivo substrate of hepsin. The identification of hepsin as the first protease involved in the release of a ZP domain protein is likely relevant for other members of this protein family, including several extracellular proteins, as egg coat proteins and inner ear tectorins.

The Ionotropic receptors IR21a and IR25a mediate cool sensing in Drosophila.

Animals rely on highly sensitive thermoreceptors to seek out optimal temperatures, but the molecular mechanisms of thermosensing are not well understood. The Dorsal Organ Cool Cells (DOCCs) of the Drosophila larva are a set of exceptionally thermosensitive neurons critical for larval cool avoidance. Here, we show that DOCC cool-sensing is mediated by Ionotropic Receptors (IRs), a family of sensory receptors widely studied in invertebrate chemical sensing. We find that two IRs, IR21a and IR25a, are required to mediate DOCC responses to cooling and are required for cool avoidance behavior. Furthermore, we find that ectopic expression of IR21a can confer cool-responsiveness in an Ir25a-dependent manner, suggesting an instructive role for IR21a in thermosensing. Together, these data show that IR family receptors can function together to mediate thermosensation of exquisite sensitivity.

Broadening the CRM domain of application to higher educational (e-learning) environments

In this paper, we reflect about the broadening of the field of application of CRM from the business domain to a wider context of relationships in which the inclusion of non-profit making organizations seems natural. In particular, we focus on analyzing the suitability of adopting CRM processes by universities and higher educational institutions dedicated to e-learning. This is an issue that, in our opinion, has much potential but has received little attention in research so far.

An ontology to automated learning scenarios? an approach to its knowledge domain

Automation or semi-automation of learning scenariospecifications is one of the least exploredsubjects in the e-learning research area. There isa need for a catalogue of learning scenarios and atechnique to facilitate automated retrieval of stored specifications. This requires constructing anontology with this goal and is justified inthis paper. This ontology must mainlysupport a specification technique for learning scenarios. This ontology should also be useful in the creation and validation of new scenarios as well as in the personalization of learning scenarios or their monitoring. Thus, after justifying the need for this ontology, a first approach of a possible knowledge domain is presented. An example of a concrete learning scenario illustrates some relevant concepts supported by this ontology in order to define the scenario in such a way that it could be easy to automate.

Expanding the Customer Relationship Management scope to the non-profit organizations : an analysis focused on the e-university domain

Peer-reviewed

Vacancy-assisted domain-growth in asymmetric binary alloys: A Monte Carlo Study

A Monte Carlo simulation study of the vacancy-assisted domain growth in asymmetric binary alloys is presented. The system is modeled using a three-state ABV Hamiltonian which includes an asymmetry term. Our simulated system is a stoichiometric two-dimensional binary alloy with a single vacancy which evolves according to the vacancy-atom exchange mechanism. We obtain that, compared to the symmetric case, the ordering process slows down dramatically. Concerning the asymptotic behavior it is algebraic and characterized by the Allen-Cahn growth exponent x51/2. The late stages of the evolution are preceded by a transient regime strongly affected by both the temperature and the degree of asymmetry of the alloy. The results are discussed and compared to those obtained for the symmetric case.

Computational Techniques for Spectral Image Analysis

Multispectral images are becoming more common in the field of remote sensing, computer vision, and industrial applications. Due to the high accuracy of the multispectral information, it can be used as an important quality factor in the inspection of industrial products. Recently, the development on multispectral imaging systems and the computational analysis on the multispectral images have been the focus of a growing interest. In this thesis, three areas of multispectral image analysis are considered. First, a method for analyzing multispectral textured images was developed. The method is based on a spectral cooccurrence matrix, which contains information of the joint distribution of spectral classes in a spectral domain. Next, a procedure for estimating the illumination spectrum of the color images was developed. Proposed method can be used, for example, in color constancy, color correction, and in the content based search from color image databases. Finally, color filters for the optical pattern recognition were designed, and a prototype of a spectral vision system was constructed. The spectral vision system can be used to acquire a low dimensional component image set for the two dimensional spectral image reconstruction. The data obtained by the spectral vision system is small and therefore convenient for storing and transmitting a spectral image.

Molecular Interactions of Prodiginines with the BH3 Domain of Anti-Apoptotic Bcl-2 Family Members.

Prodigiosin and obatoclax, members of the prodiginines family, are small molecules with anti-cancer properties that are currently under preclinical and clinical trials. The molecular target(s) of these agents, however, is an open question. Combining experimental and computational techniques we find that prodigiosin binds to the BH3 domain in some BCL-2 protein families, which play an important role in the apoptotic programmed cell death. In particular, our results indicate a large affinity of prodigiosin for MCL-1, an anti-apoptotic member of the BCL-2 family. In melanoma cells, we demonstrate that prodigiosin activates the mitochondrial apoptotic pathway by disrupting MCL-1/BAK complexes. Computer simulations with the PELE software allow the description of the induced fit process, obtaining a detailed atomic view of the molecular interactions. These results provide new data to understand the mechanism of action of these molecules, and assist in the development of more specific inhibitors of anti-apoptotic BCL-2 proteins.

Photomultiplier nonlinear response in time-domain laser-induced luminescence spectroscopy

A new procedure to find the limiting range of the photomultiplier linear response of a low-cost, digital oscilloscope-based time-resolved laser-induced luminescence spectrometer (TRLS), is presented. A systematic investigation on the instrument response function with different signal input terminations, and the relationship between the luminescence intensity reaching the photomultiplier and the measured decay time are described. These investigations establish that setting the maximum intensity of the luminescence signal below 0.3V guarantees, for signal input terminations equal or higher than 99.7 ohm, a linear photomultiplier response.