Induction of the alternative NF-κB pathway by lymphotoxin αβ (LTαβ) relies on internalization of LTβ receptor.

Several tumor necrosis factor receptor (TNFR) family members activate both the classical and the alternative NF-κB pathways. However, how a single receptor engages these two distinct pathways is still poorly understood. Using lymphotoxin β receptor (LTβR) as a prototype, we showed that activation of the alternative, but not the classical, NF-κB pathway relied on internalization of the receptor. Further molecular analyses revealed a specific cytosolic region of LTβR essential for its internalization, TRAF3 recruitment, and p100 processing. Interestingly, we found that dynamin-dependent, but clathrin-independent, internalization of LTβR appeared to be required for the activation of the alternative, but not the classical, NF-κB pathway. In vivo, ligand-induced internalization of LTβR in mesenteric lymph node stromal cells correlated with induction of alternative NF-κB target genes. Thus, our data shed light on LTβR cellular trafficking as a process required for specific biological functions of NF-κB.

Ly49D engagement on T lymphocytes induces TCR-independent activation and CD8 effector functions that control tumor growth.

Recent data showing expression of activating NK receptors (NKR) by conventional T lymphocytes raise the question of their role in the triggering of TCR-independent responses that could be damaging for the host. Transgenic mice expressing the activating receptor Ly49D/DAP12 offer the opportunity to better understand the relevance of ITAM signaling in the biology of T cells. In vitro experiments showed that Ly49D engagement on T lymphocytes by a cognate MHC class I ligand expressed by Chinese hamster ovary (CHO) cells or by specific Ab triggered cellular activation of both CD4 and CD8 populations with modulation of activation markers and cytokine production. The forced expression of the ITAM signaling chain DAP12 is mandatory for Ly49D-transgenic T cell activation. In addition, Ly49D stimulation induced T lymphocyte proliferation, which was much stronger for CD8 T cells. Phenotypic analysis of anti-Ly49D-stimulated CD8 T cells and their ability to produce high levels of IFN-gamma and to kill target cells indicate that Ly49D ligation generates effector cytotoxic CD8 T cells. Ly49D engagement by itself also triggered cytotoxic activity of activated CD8 T cells. Adoptive transfer experiments confirmed that Ly49D-transgenic CD8 T cells are able to control growth of CHO tumor cells or RMA cells transfected with Hm1-C4, the Ly49D ligand normally expressed by CHO. In conclusion, Ly49D engagement on T cells leads to T cell activation and to a full range of TCR-independent effector functions of CD8 T cells.

A clathrin-dependent pathway leads to KRas signaling on late endosomes en route to lysosomes

Ras proteins are small guanosine triphosphatases involved in the regulation of important cellular functions such as proliferation, differentiation, and apoptosis. Understanding the intracellular trafficking of Ras proteins is crucial to identify novel Ras signaling platforms. In this study, we report that epidermal growth factor triggers Kirsten Ras (KRas) translocation onto endosomal membranes (independently of calmodulin and protein kinase C phosphorylation) through a clathrin-dependent pathway. From early endosomes, KRas but not Harvey Ras or neuroblastoma Ras is sorted and transported to late endosomes (LEs) and lysosomes. Using yellow fluorescent protein¿Raf1 and the Raichu-KRas probe, we identified for the first time in vivo¿active KRas on Rab7 LEs, eliciting a signal output through Raf1. On these LEs, we also identified the p14¿MP1 scaffolding complex and activated extracellular signal-regulated kinase 1/2. Abrogation of lysosomal function leads to a sustained late endosomal mitogen-activated protein kinase signal output. Altogether, this study reveals novel aspects about KRas intracellular trafficking and signaling, shedding new light on the mechanisms controlling Ras regulation in the cell.

Microinductive signal conditioning with resonant differential filters: high-sensitivity biodetection applications

Inductive-based devices integrated with Si technology for biodetection applications are characterized, using simple resonant differential filter configurations. This has allowed the corroboration of the viability of the proposed circuits, which are characterized by their very high simplicity, for microinductive signal conditioning in high-sensitivity sensor devices. The simulation of these simple circuits predicts sensitivities of the differential output voltage which can achieve values in the range of 0.1-1 V/nH, depending on the coil parameters. These very high-sensitivity values open the possibility for the experimental detection of extremely small inductance changes in the devices. For real microinductive devices, both series resistance and parasitic capacitive components contribute to the decrease of the differential circuit sensitivity. Nevertheless, measurements performed using micro-coils fabricated with relatively high series resistance and coupling parasitic effects have allowed detection of changes in the range of 2 nH. which are compatible with biodetection applications with estimated detection limits below the picomolarity range.

Carboxyl terminus structural requirements for glycosyl-phosphatidylinositol anchor addition to cell surface proteins.

Glycosyl phosphatidylinositol (GPI)-anchored proteins contain in their COOH-terminal region a peptide segment that is thought to direct glycolipid addition. This signal has been shown to require a pair of small amino acids positioned 10-12 residues upstream of an hydrophobic C-terminal domain. We analysed the contribution of the region separating the anchor acceptor site and the C-terminal hydrophobic segment by introducing amino acid deletions and substitutions in the spacer element of the GPI-anchored Thy-1 glycoprotein. Deletions of 7 amino acids in this region, as well as the introduction of 2 charged residues, prevented the glycolipid addition to Thy-1, suggesting that the length and the primary sequence of the spacer domain are important determinants in the signal directing GPI anchor transfer onto a newly synthesized polypeptide. Furthermore, we tested these rules by creating a truncated form of the normally transmembranous Herpes simplex virus I glycoprotein D (gDI) and demonstrating that when its C-terminal region displays all the features of a GPI-anchored protein, it is able to direct glycolipid addition onto another cell surface molecule.

Transfer insensitive labeling technique (TILT): application to multislice functional perfusion imaging.

Cerebral blood flow can be studied in a multislice mode with a recently proposed perfusion sequence using inversion of water spins as an endogenous tracer without magnetization transfer artifacts. The magnetization transfer insensitive labeling technique (TILT) has been used for mapping blood flow changes at a microvascular level under motor activation in a multislice mode. In TILT, perfusion mapping is achieved by subtraction of a perfusion-sensitized image from a control image. Perfusion weighting is accomplished by proximal blood labeling using two 90 degrees radiofrequency excitation pulses. For control preparation the labeling pulses are modified such that they have no net effect on blood water magnetization. The percentage of blood flow change, as well as its spatial extent, has been studied in single and multislice modes with varying delays between labeling and imaging. The average perfusion signal change due to activation was 36.9 +/- 9.1% in the single-slice experiments and 38.1 +/- 7.9% in the multislice experiments. The volume of activated brain areas amounted to 1.51 +/- 0.95 cm3 in the contralateral primary motor (M1) area, 0.90 +/- 0.72 cc in the ipsilateral M1 area, 1.27 +/- 0.39 cm3 in the contralateral and 1.42 +/- 0.75 cm3 in the ipsilateral premotor areas, and 0.71 +/- 0.19 cm3 in the supplementary motor area.

CHARACTERIZATION OF NrsZ, A NOVEL SMALL REGULATORY NON-CODING RNA INVOLVED IN THE ADAPTATION OF PSEUDOMONAS AERUGINOSA PAO1

The opportunistic ubiquitous pathogen Pseudomonas aeruginosa strain PAOl is a versatile Gram-negative bacterium that has the extraordinary capacity to colonize a wide diversity of ecological niches and to cause severe and persistent infections in humans. To ensure an optimal coordination of the genes involved in nutrient utilization, this bacterium uses the NtrB/C and/or the CbrA/B two-component systems, to sense nutrients availability and to regulate in consequence the expression of genes involved in their uptake and catabolism. NtrB/C is specialized in nitrogen utilization, while the CbrA/B system is involved in both carbon and nitrogen utilization and both systems activate their target genes expression in concert with the alternative sigma factor RpoN. Moreover, the NtrB/C and CbrA/B two- component systems regulate the secondary metabolism of the bacterium, such as the production of virulence factors. In addition to the fine-tuning transcriptional regulation, P. aeruginosa can rapidly modulate its metabolism using small non-coding regulatory RNAs (sRNAs), which regulate gene expression at the post-transcriptional level by diverse and sophisticated mechanisms and contribute to the fast physiological adaptability of this bacterium. In our search for novel RpoN-dependent sRNAs modulating the nutritional adaptation of P. aeruginosa PAOl, we discovered NrsZ (Nitrogen regulated sRNA), a novel RpoN-dependent sRNA that is induced under nitrogen starvation by the NtrB/C two-component system. NrsZ has a unique architecture, formed of three similar stem-loop structures (SL I, II and II) separated by variant spacer sequences. Moreover, this sRNA is processed in short individual stem-loop molecules, by internal cleavage involving the endoribonuclease RNAse E. Concerning NrsZ functions in P. aeruginosa PAOl, this sRNA was shown to trigger the swarming motility and the rhamnolipid biosurfactants production. This regulation is due to the NrsZ-mediated activation of rhlA expression, a gene encoding for an enzyme essential for swarming motility and rhamnolipids production. Interestingly, the SL I structure of NrsZ ensures its regulatory function on rhlA expression, suggesting that the similar SLs are the functional units of this modular sRNA. However, the regulatory mechanism of action of NrsZ on rhlA expression activation remains unclear and is currently being investigated. Additionally, the NrsZ regulatory network was investigated by a transcriptome analysis, suggesting that numerous genes involved in both primary and secondary metabolism are regulated by this sRNA. To emphasize the importance of NrsZ, we investigated its conservation in other Pseudomonas species and demonstrated that NrsZ is conserved and expressed under nitrogen limitation in Pseudomonas protegens Pf-5, Pseudomonas putida KT2442, Pseudomonas entomophila L48 and Pseudomonas syringae pv. tomato DC3000, strains having different ecological features, suggesting an important role of NrsZ in the adaptation of Pseudomonads to nitrogen starvation. Interestingly the architecture of the different NrsZ homologs is similarly composed by SL structures and variant spacer sequences. However, the number of SL repetitions is not identical, and one to six SLs were predicted on the different NrsZ homologs. Moreover, NrsZ is processed in short molecules in all the strains, similarly to what was previously observed in P. aeruginosa PAOl, and the heterologous expression of the NrsZ homologs restored rhlA expression, swarming motility and rhamnolipids production in the P. aeruginosa NrsZ mutant. In many aspects, NrsZ is an atypical sRNA in the bacterial panorama. To our knowledge, NrsZ is the first described sRNA induced by the NtrB/C. Moreover, its unique modular architecture and its processing in similar short SL molecules suggest that NrsZ belongs to a novel family of bacterial sRNAs. -- L'agent pathogène opportuniste et ubiquitaire Pseudomonas aeruginosa souche PAOl est une bactérie Gram négative versatile ayant l'extraordinaire capacité de coloniser différentes niches écologiques et de causer des infections sévères et persistantes chez l'être humain. Afin d'assurer une coordination optimale des gènes impliqués dans l'utilisation de différents nutriments, cette bactérie se sert de systèmes à deux composants tel que NtrB/C et CbrA/B afin de détecter la disponibilité des ressources nutritives, puis de réguler en conséquence l'expression des gènes impliqués dans leur importation et leur catabolisme. Le système NtrB/C régule l'utilisation des sources d'azote alors que le système CbrA/B est impliqué à la fois dans l'utilisation des sources de carbone et d'azote. Ces deux systèmes activent l'expression de leurs gènes-cibles de concert avec le facteur sigma alternatif RpoN. En outre, NtrB/C et CbrA/B régulent aussi le métabolisme secondaire, contrôlant notamment la production d'importants facteurs de virulence. En plus de toutes ces régulations génétiques fines ayant lieu au niveau transcriptionnel, P. aeruginosa est aussi capable de moduler son métabolisme en se servant de petits ARNs régulateurs non-codants (ARNncs), qui régulent l'expression génétique à un niveau post- transcriptionnel par divers mécanismes sophistiqués et contribuent à rendre particulièrement rapide l'adaptation physiologique de cette bactérie. Au cours de nos recherches sur de nouveaux ARNncs dépendant du facteur sigma RpoN et impliqués dans l'adaptation nutritionnelle de P. aeruginosa PAOl, nous avons découvert NrsZ (Nitrogen regulated sRNA), un ARNnc induit par la cascade NtrB/C-RpoN en condition de carence en azote. NrsZ a une architecture unique, composée de trois structures en tige- boucle (TB I, II et III) hautement similaires et séparées par des « espaceurs » ayant des séquences variables. De plus, cet ARNnc est clivé en petits fragments correspondant au trois molécules en tige-boucle, par un processus de clivage interne impliquant l'endoribonucléase RNase E. Concernant les fonctions de NrsZ chez P. aeruginosa PAOl, cet ARNnc est capable d'induire la motilité de type « swarming » et la production de biosurfactants, nommés rhamnolipides. Cette régulation est due à l'activation par NrsZ de l'expression de rhlA, un gène essentiel pour la motilité de type swarming et pour la production de rhamnolipides. Étonnamment, la structure TB I est capable d'assurer à elle seule la fonction régulatrice de NrsZ sur l'expression de rhlA, suggérant que ces molécules TBs sont les unités fonctionnelles de cet ARNnc modulaire. Cependant, le mécanisme moléculaire par lequel NrsZ active l'expression de rhlA demeure à ce jour incertain et est actuellement à l'étude. En plus, le réseau de régulations médiées par NrsZ a été étudié par une analyse de transcriptome qui a indiqué que de nombreux gènes impliqués dans le métabolisme primaire ou secondaire seraient régulés par NrsZ. Pour accentuer l'importance de NrsZ, nous avons étudié sa conservation dans d'autres espèces de Pseudomonas. Ainsi, nous avons démontré que NrsZ est conservé et exprimé en situation de carence d'azote par les souches Pseudomonas protegens Pf-5, Pseudomonas putida KT2442, Pseudomonas entomophila L48, Pseudomonas syringae pv. tomato DC3000, quatre espèces ayant des caractéristiques écologiques très différentes, suggérant que NrsZ joue un rôle important dans l'adaptation du genre Pseudomonas envers la carence en azote. Chez toutes les souches étudiées, les différents homologues de NrsZ présentent une architecture similaire faite de TBs conservées et d'espaceurs. Cependant, le nombre de TBs n'est pas identique et peut varier de une à six copies selon la souche. Les différentes versions de NrsZ sont clivées en petites molécules dans ces quatre souches, comme il a été observé chez P. aeruginosa PAOl. De plus, l'expression hétérologue des différentes variantes de NrsZ est capable de restaurer l'expression de rhlA, la motilité swarming et la production de rhamnolipides dans une souche de P. aeruginosa dont nrsZ a été inactivé. Par bien des aspects, NrsZ est un ARNnc atypique dans le monde bactérien. À notre connaissance, NrsZ est le premier ARNnc décrit comme étant régulé par le système NtrB/C. De plus, son unique architecture modulaire et son clivage en petites molécules similaires suggèrent que NrsZ appartient à une nouvelle famille d'ARNncs bactériens.

Cost-effective experimental design to support modeling of concentration-response functions

Modeling concentration-response function became extremely popular in ecotoxicology during the last decade. Indeed, modeling allows determining the total response pattern of a given substance. However, reliable modeling is consuming in term of data, which is in contradiction with the current trend in ecotoxicology, which aims to reduce, for cost and ethical reasons, the number of data produced during an experiment. It is therefore crucial to determine experimental design in a cost-effective manner. In this paper, we propose to use the theory of locally D-optimal designs to determine the set of concentrations to be tested so that the parameters of the concentration-response function can be estimated with high precision. We illustrated this approach by determining the locally D-optimal designs to estimate the toxicity of the herbicide dinoseb on daphnids and algae. The results show that the number of concentrations to be tested is often equal to the number of parameters and often related to the their meaning, i.e. they are located close to the parameters. Furthermore, the results show that the locally D-optimal design often has the minimal number of support points and is not much sensitive to small changes in nominal values of the parameters. In order to reduce the experimental cost and the use of test organisms, especially in case of long-term studies, reliable nominal values may therefore be fixed based on prior knowledge and literature research instead of on preliminary experiments

Intensity correlation functions of dye lasers: Comparison of colored-gain-noise and colored-loss-noise models

The intensity correlation functions C(t) for the colored-gain-noise model of dye lasers are analyzed and compared with those for the loss-noise model. For correlation times ¿ larger than the deterministic relaxation time td, we show with the use of the adiabatic approximation that C(t) values coincide for both models. For small correlation times we use a method that provides explicit expressions of non-Markovian correlation functions, approximating simultaneously short- and long-time behaviors. Comparison with numerical simulations shows excellent results simultaneously for short- and long-time regimes. It is found that, when the correlation time of the noise increases, differences between the gain- and loss-noise models tend to disappear. The decay of C(t) for both models can be described by a time scale that approaches the deterministic relaxation time. However, in contrast with the loss-noise model, a secondary time scale remains for large times for the gain-noise model, which could allow one to distinguish between both models.

Manipulating the sensitivity of signal-induced repression: quantification and consequences of altered brinker gradients.

Traditionally, the analysis of gene regulatory regions suffered from the caveat that it was restricted to artificial contexts (e.g. reporter constructs of limited size). With the advent of the BAC recombineering technique, genomic constructs can now be generated to test regulatory elements in their endogenous environment. The expression of the transcriptional repressor brinker (brk) is negatively regulated by Dpp signaling. Repression is mediated by small sequence motifs, the silencer elements (SEs), that are present in multiple copies in the regulatory region of brk. In this work, we manipulated the SEs in the brk locus. We precisely quantified the effects of the individual SEs on the Brk gradient in the wing disc by employing a 1D data extraction method, followed by the quantification of the data with reference to an internal control. We found that mutating the SEs results in an expansion of the brk expression domain. However, even after mutating all predicted SEs, repression could still be observed in regions of maximal Dpp levels. Thus, our data point to the presence of additional, low affinity binding sites in the brk locus.

Velocity cross-correlations and atomic momentum transfer in simple liquids with different potential cores

Time correlation functions between the velocity of a tagged particle and velocities of particles within specified ranges of initial separations have been obtained by molecular dynamics simulation. These correlation functions have allowed us to analyze the momentum transfer between particles in different coordination shells. Two simple liquids at very different densities and two purely repulsive potentials with very different softnesses have been considered. The longitudinal correlations, which are the velocity cross-correlations along the initial direction defined by the centers of two given particles, have been calculated separately. It has been proven that these correlations should be attributed to particles both in front of and behind the central one. As with propagating longitudinal modes, they are strongly dependent on the softness of the potential core. Some characteristic features of the velocity correlation functions after the initial rise should be related to nonlongitudinal correlations. It has been shown that velocity cross-correlations between distinct particles cannot only be attributed to the direct interactions among particles, but also to the motions induced by the movement of a tagged particle on their neighbors.

Interhemispheric visual integration in humans explored by multimodal brain imaging

Résumé: Les récents progrès techniques de l'imagerie cérébrale non invasives ont permis d'améliorer la compréhension des différents systèmes fonctionnels cérébraux. Les approches multimodales sont devenues indispensables en recherche, afin d'étudier dans sa globalité les différentes caractéristiques de l'activité neuronale qui sont à la base du fonctionnement cérébral. Dans cette étude combinée d'imagerie par résonance magnétique fonctionnelle (IRMf) et d'électroencéphalographie (EEG), nous avons exploité le potentiel de chacune d'elles, soit respectivement la résolution spatiale et temporelle élevée. Les processus cognitifs, de perception et de mouvement nécessitent le recrutement d'ensembles neuronaux. Dans la première partie de cette thèse nous étudions, grâce à la combinaison des techniques IRMf et EEG, la réponse des aires visuelles lors d'une stimulation qui demande le regroupement d'éléments cohérents appartenant aux deux hémi-champs visuels pour en faire une seule image. Nous utilisons une mesure de synchronisation (EEG de cohérence) comme quantification de l'intégration spatiale inter-hémisphérique et la réponse BOLD (Blood Oxygenation Level Dependent) pour évaluer l'activité cérébrale qui en résulte. L'augmentation de la cohérence de l'EEG dans la bande beta-gamma mesurée au niveau des électrodes occipitales et sa corrélation linéaire avec la réponse BOLD dans les aires de VP/V4, reflète et visualise un ensemble neuronal synchronisé qui est vraisemblablement impliqué dans le regroupement spatial visuel. Ces résultats nous ont permis d'étendre la recherche à l'étude de l'impact que le contenu en fréquence des stimuli a sur la synchronisation. Avec la même approche, nous avons donc identifié les réseaux qui montrent une sensibilité différente à l'intégration des caractéristiques globales ou détaillées des images. En particulier, les données montrent que l'implication des réseaux visuels ventral et dorsal est modulée par le contenu en fréquence des stimuli. Dans la deuxième partie nous avons a testé l'hypothèse que l'augmentation de l'activité cérébrale pendant le processus de regroupement inter-hémisphérique dépend de l'activité des axones calleux qui relient les aires visuelles. Comme le Corps Calleux présente une maturation progressive pendant les deux premières décennies, nous avons analysé le développement de la fonction d'intégration spatiale chez des enfants âgés de 7 à 13 ans et le rôle de la myelinisation des fibres calleuses dans la maturation de l'activité visuelle. Nous avons combiné l'IRMf et la technique de MTI (Magnetization Transfer Imaging) afin de suivre les signes de maturation cérébrale respectivement sous l'aspect fonctionnel et morphologique (myelinisation). Chez lés enfants, les activations associées au processus d'intégration entre les hémi-champs visuels sont, comme chez l'adulte, localisées dans le réseau ventral mais se limitent à une zone plus restreinte. La forte corrélation que le signal BOLD montre avec la myelinisation des fibres du splenium est le signe de la dépendance entre la maturation des fonctions visuelles de haut niveau et celle des connections cortico-corticales. Abstract: Recent advances in non-invasive brain imaging allow the visualization of the different aspects of complex brain dynamics. The approaches based on a combination of imaging techniques facilitate the investigation and the link of multiple aspects of information processing. They are getting a leading tool for understanding the neural basis of various brain functions. Perception, motion, and cognition involve the formation of cooperative neuronal assemblies distributed over the cerebral cortex. In this research, we explore the characteristics of interhemispheric assemblies in the visual brain by taking advantage of the complementary characteristics provided by EEG (electroencephalography) and fMRI (Functional Magnetic Resonance Imaging) techniques. These are the high temporal resolution for EEG and high spatial resolution for fMRI. In the first part of this thesis we investigate the response of the visual areas to the interhemispheric perceptual grouping task. We use EEG coherence as a measure of synchronization and BOLD (Blood Oxygenar tion Level Dependent) response as a measure of the related brain activation. The increase of the interhemispheric EEG coherence restricted to the occipital electrodes and to the EEG beta band and its linear relation to the BOLD responses in VP/V4 area points to a trans-hemispheric synchronous neuronal assembly involved in early perceptual grouping. This result encouraged us to explore the formation of synchronous trans-hemispheric networks induced by the stimuli of various spatial frequencies with this multimodal approach. We have found the involvement of ventral and medio-dorsal visual networks modulated by the spatial frequency content of the stimulus. Thus, based on the combination of EEG coherence and fMRI BOLD data, we have identified visual networks with different sensitivity to integrating low vs. high spatial frequencies. In the second part of this work we test the hypothesis that the increase of brain activity during perceptual grouping depends on the activity of callosal axons interconnecting the visual areas that are involved. To this end, in children of 7-13 years, we investigated functional (functional activation with fMRI) and morphological (myelination of the corpus callosum with Magnetization Transfer Imaging (MTI)) aspects of spatial integration. In children, the activation associated with the spatial integration across visual fields was localized in visual ventral stream and limited to a part of the area activated in adults. The strong correlation between individual BOLD responses in .this area and the myelination of the splenial system of fibers points to myelination as a significant factor in the development of the spatial integration ability.

Connections between signal processing and complex analysis

We describe one of the research lines of the Grup de Teoria de Funcions de la UAB UB, which deals with sampling and interpolation problems in signal analysis and their connections with complex function theory.

Influence of bedrock structures on the spatial pattern of erosional landforms in small alpine catchments

Structural settings and lithological characteristics are traditionally assumed to influence the development of erosional landforms, such as gully networks and rock couloirs, in steep mountain rock basins. The structural control of erosion of two small alpine catchments of distinctive rock types is evaluated by comparing the correspondences between the orientations of their gullies and rock couloirs with (1) the sliding orientations of potential slope failures mechanisms, and (2) the orientation of the maximum joint frequency, this latter being considered as the direction exploited primarily by erosion and mass wasting processes. These characteristic orientations can be interpreted as structural weaknesses contributing to the initiation and propagation of erosion. The morphostructural analysis was performed using digital elevation models and field observations. The catchment comprised of magmatic intrusive rocks shows a clear structural control, mostly expressed through potential wedges failure. Such joint configurations have a particular geometry that encourages the development of gullies in hard rock, e.g. through enhanced gravitational and hydrological erosional processes. In the catchment underlain by sedimentary rocks, penetrative joints that act as structural weaknesses seem to be exploited by gullies and rock couloirs. However, the lithological setting and bedding configuration prominently control the development of erosional landforms, and influence not only the local pattern of geomorphic features, but the general morphology of the catchment. The orientations of the maximum joint frequency are clearly associated with the gully network, suggesting that its development is governed by anisotropy in rock strength. These two catchments are typical of bedrock-dominated basins prone to intense processes of debris supply. This study suggests a quantitative approach for describing the relationship between bedrock jointing and geomorphic features geometry. Incorporation of bedrock structure can be relevant when studying processes governing the transfer of clastic material, for the assessment of sediment yields and in landforms evolution models.

Novel acid phosphatase in Candida glabrata suggests selective pressure and niche specialization in the phosphate signal transduction pathway.

Evolution through natural selection suggests unnecessary genes are lost. We observed that the yeast Candida glabrata lost the gene encoding a phosphate-repressible acid phosphatase (PHO5) present in many yeasts including Saccharomyces cerevisiae. However, C. glabrata still had phosphate starvation-inducible phosphatase activity. Screening a C. glabrata genomic library, we identified CgPMU2, a member of a three-gene family that contains a phosphomutase-like domain. This small-scale gene duplication event could allow for sub- or neofunctionalization. On the basis of phylogenetic and biochemical characterizations, CgPMU2 has neofunctionalized to become a broad range, phosphate starvation-regulated acid phosphatase, which functionally replaces PHO5 in this pathogenic yeast. We determined that CgPmu2, unlike ScPho5, is not able to hydrolyze phytic acid (inositol hexakisphosphate). Phytic acid is present in fruits and seeds where S. cerevisiae grows, but is not abundant in mammalian tissues where C. glabrata grows. We demonstrated that C. glabrata is limited from an environment where phytic acid is the only source of phosphate. Our work suggests that during evolutionary time, the selection for the ancestral PHO5 was lost and that C. glabrata neofunctionalized a weak phosphatase to replace PHO5. Convergent evolution of a phosphate starvation-inducible acid phosphatase in C. glabrata relative to most yeast species provides an example of how small changes in signal transduction pathways can mediate genetic isolation and uncovers a potential speciation gene.