A novel p21-activated kinase binds the actin and microtubule networks and induces microtubule stabilization

Coordination of the different cytoskeleton networks in the cell is of central importance for morphogenesis, organelle transport, and motility. The Rho family proteins are well characterized for their effects on the actin cytoskeleton, but increasing evidence indicates that they may also control microtubule (MT) dynamics. Here, we demonstrate that a novel Cdc42/Rac effector, X-p21-activated kinase (PAK)5, colocalizes and binds to both the actin and MT networks and that its subcellular localization is regulated during cell cycle progression. In transfected cells, X-PAK5 promotes the formation of stabilized MTs that are associated in bundles and interferes with MTs dynamics, slowing both the elongation and shrinkage rates and inducing long paused periods. X-PAK5 subcellular localization is regulated tightly, since coexpression with active Rac or Cdc42 induces its shuttling to actin-rich structures. Thus, X-PAK5 is a novel MT-associated protein that may communicate between the actin and MT networks during cellular responses to environmental conditions

Geochronological and geochemical characterization of magmatic-hydrothermal events within the Southern Variscan external domain (Ce'vennes area, France)

International audienceGeochronological, mineralogical, and geochemical analyses have been focussed on the Mont-Loze're- Borne plutonic complex and surrounding rocks (Ce'vennes, French Massif Central) in which B-W-Sn and As-Au-Sb mineralization is encountered. Two main results are highlighted: (1) the existence of a 301-306 Ma magmatohydrothermal event unrelated to the emplacement of the Pont-de-Montvert-Borne plutonic body at 316 Ma; (2) the magmatic and hydrothermal features are strongly associated, both in time and in space, thus demonstrating an intimate connection between mineralizing processes and magmatism in this part of the French Massif Central. We also show that mineralization and associated hydrothermal occurrences do not correspond to a simple and single geochemical signature and that a contamination model must be invoked in order to account for the complexity of isotopic results. This study demonstrates that the application of the O and H isotopic signatures as tracers of the source and nature of fluids in an orogenic context requires some specific care. Finally, a model of the tectonic-magmatic- hydrothermal evolution of the study area is suggested in which we discuss two alternative scenarios. The first one implies the existence of two different hydrothermal/ mineralizing events (Bo-W-Sn and As-Au-Sb ones). The second one suggests the same source for all hydrothermal and mineralized structures

Analysis of cellular responses of macrophages to zinc ions and zinc oxide nanoparticles: a combined targeted and proteomic approach

Two different zinc oxide nanoparticles, as well as zinc ions, are used to study the cellular responses of the RAW 264 macrophage cell line. A proteomic screen is used to provide a wide view of the molecular effects of zinc, and the most prominent results are cross-validated by targeted studies. Furthermore, the alteration of important macrophage functions (e.g. phagocytosis) by zinc is also investigated. The intracellular dissolution/uptake of zinc is also studied to further characterize zinc toxicity. Zinc oxide nanoparticles dissolve readily in the cells, leading to high intracellular zinc concentrations, mostly as protein-bound zinc. The proteomic screen reveals a rather weak response in the oxidative stress response pathway, but a strong response both in the central metabolism and in the proteasomal protein degradation pathway. Targeted experiments confirm that carbohydrate catabolism and proteasome are critical determinants of sensitivity to zinc, which also induces DNA damage. Conversely, glutathione levels and phagocytosis appear unaffected at moderately toxic zinc concentrations

Molecular responses of mouse macrophages to copper and copper oxide nanoparticles inferred from proteomic analyses

The molecular responses of macrophages to copper-based nanoparticles have been investigated via a combination of proteomic and biochemical approaches, using the RAW264.7 cell line as a model. Both metallic copper and copper oxide nanoparticles have been tested, with copper ion and zirconium oxide nanoparticles used as controls. Proteomic analysis highlighted changes in proteins implicated in oxidative stress responses (superoxide dismutases and peroxiredoxins), glutathione biosynthesis, the actomyosin cytoskeleton, and mitochondrial proteins (especially oxidative phosphorylation complex subunits). Validation studies employing functional analyses showed that the increases in glutathione biosynthesis and in mitochondrial complexes observed in the proteomic screen were critical to cell survival upon stress with copper-based nanoparticles; pharmacological inhibition of these two pathways enhanced cell vulnerability to copper-based nanoparticles, but not to copper ions. Furthermore, functional analyses using primary macrophages derived from bone marrow showed a decrease in reduced glutathione levels, a decrease in the mitochondrial transmembrane potential, and inhibition of phagocytosis and of lipopolysaccharide-induced nitric oxide production. However, only a fraction of these effects could be obtained with copper ions. In conclusion, this study showed that macrophage functions are significantly altered by copper-based nanoparticles. Also highlighted are the cellular pathways modulated by cells for survival and the exemplified cross-toxicities that can occur between copper-based nanoparticles and pharmacological agents

Гранитоиды обрамления Криворожской структуры. Проблемы корреляции геологических тел и комплексов

Current population genetic models fail to cope with genetic differentiation for species with large, contiguous and heterogeneous distribution. We show that in such a case, genetic differentiation can be predicted at equilibrium by circuit theory, where conductance corresponds to abundance in species distribution models (SDM). Circuit-SDM approach was used for the phylogeographic study of the lepidopteran cereal stemborer Busseola fusca Füller (Noctuidae) across sub-Saharan Africa. Species abundance was surveyed across its distribution range. SDM models were optimized and selected by cross validation. Relationship between observed matrices of genetic differentiation between individuals, and matrices of resistance distance was assessed through Mantel tests and redundancy discriminant analyses (RDA). A total of 628 individuals from 130 localities in 17 countries were genotyped at 7 microsatellite loci. Six population clusters were found based on a Bayesian analysis. The eastern margin of Dahomey Gap between East and West Africa was the main factor of genetic differentiation. The SDM projections at present, last interglacial and last glacial maximum periods were used for estimation of circuit resistance between locations of genotyped individuals. For all periods of time, when using either all individuals or only East-African individuals, partial Mantel r and RDA analyses conditioning on geographic distance were found significant. Under future projections (year 2080), partial r and RDA significance were different. From this study, it is concluded that analytical solutions provided by circuit theory are useful for the evolutionary management of populations and for phylogeographic analysis when coalescence times are not accessible by approximate Bayesian simulations

A Soluble Form of the Triggering Receptor Expressed on Myeloid Cells-1 Modulates the Inflammatory Response in Murine Sepsis

The triggering receptor expressed on myeloid cells (TREM)-1 is a recently discovered receptor expressed on the surface of neutrophils and a subset of monocytes. Engagement of TREM-1 has been reported to trigger the synthesis of proinflammatory cytokines in the presence of microbial products. Previously, we have identified a soluble form of TREM-1 (sTREM-1) and observed significant levels in serum samples from septic shock patients but not controls. Here, we investigated its putative role in the modulation of inflammation during sepsis. We observed that sTREM-1 was secreted by monocytes activated in vitro by LPS and in the serum of animals involved in an experimental model of septic shock. Both in vitro and in vivo, a synthetic peptide mimicking a short highly conserved domain of sTREM-1 appeared to attenuate cytokine production by human monocytes and protect septic animals from hyper-responsiveness and death. This peptide seemed to be efficient not only in preventing but also in down-modulating the deleterious effects of proinflammatory cytokines. These data suggest that in vivo modulation of TREM-1 by sTREM peptide might be a suitable therapeutic tool for the treatment of sepsis

Morphological, structural, optical, and electrical study of nanostructured thin films: Charge transport mechanism of p-type Co3O4

Morphological, structural, optical, and electrical study of nanostructured thin films: Charge transport mechanism of p-type Co3O

Review. Divergent selection for residual feed intake in the growing pig

To view supplementary material for this article, please visit https:/doi.org/10.1017/S175173111600286XThis review summarizes the results from the INRA (Institut National de la Recherche Agronomique) divergent selection experiment on residual feed intake (RFI) in growing Large White pigs during nine generations of selection. It discusses the remaining challenges and perspectives for the improvement of feed efficiency in growing pigs. The impacts on growing pigs raised under standard conditions and in alternative situations such as heat stress, inflammatory challenges or lactation have been studied. After nine generations of selection, the divergent selection for RFI led to highly significant ( P<0.001) line differences for RFI (−165 g/day in the low RFI (LRFI) line compared with high RFI line) and daily feed intake (−270 g/day). Low responses wereobserved on growth rate (−12.8 g/day, P <0.05) and body composition (+0.9mm backfat thickness, P = 0.57; −2.64% lean meat content, P<0.001) with a marked response on feed conversion ratio (−0.32 kg feed/kg gain, P<0.001). Reduced ultimate pH and increased lightness of the meat ( P<0.001) were observed in LRFI pigs with minor impact on the sensory quality of the meat. These changes in meat quality were associated with changes of the muscular energy metabolism. Reduced maintenance energy requirements (−10% after five generations of selection) and activity (−21% of time standing after six generations of selection) of LRFI pigs greatly contributed to the gain in energy efficiency. However, the impact of selection for RFI on the protein metabolism of the pig remains unclear. Digestibility of energy and nutrients was not affected by selection, neither for pigs fed conventional diets nor for pigs fed high-fibre diets. A significant improvement of digestive efficiency could likely be achieved by selecting pigs on fibre diets. No convincing genetic or blood biomarker has been identified for explaining the differences in RFI, suggesting that pigs have various ways to achieve an efficient use of feed. No deleterious impact of the selection on the sow reproduction performance was observed. The resource allocation theory states that low RFI may reduce the ability to cope with stressors,via the reduction of a buffer compartment dedicated to responses to stress. None of the experiments focussed on the response of pigs to stress or challenges could confirm this theory. Understanding the relationships between RFI and responses to stress and energy demanding processes, as such immunity and lactation, remains a major challenge for a better understanding of the underlying biological mechanisms of the trait and to reconcile the experimental results with the resource allocation theory

In- and out-plane transport properties of chemical vapor deposited TiO2 anatase films

Due to their polymorphism, TiO2 films are quintessential components of state-of-the-art functional materials and devices for various applications from dynamic random access memory to solar water splitting. However, contrary to other semiconductors/dielectric materials, the relationship between structural/morphological and electrical properties at the nano and microscales remains unclear. In this context, the morphological characteristics of TiO2 films obtained by metal–organic chemical vapor deposition (MOCVD) and plasma-enhanced chemical vapor deposition (PECVD), the latter including nitrogen doping, are investigated and they are linked to their in- and out-plane electrical properties. A transition from dense to tree-like columnar morphology is observed for the MOCVD films with increasing deposition temperature. It results in the decrease in grain size and the increase in porosity and disorder, and subsequently, it leads to the decrease in lateral carrier mobility. The increase in nitrogen amount in the PECVD films enhances the disorder in their pillar-like columnar morphology along with a slight increase in density. A similar behavior is observed for the out-plane current between the low temperature MOCVD films and the undoped PECVD ones. The pillar-like structure of the latter presents a lower in-plane resistivity than the low temperature MOCVD films, whereas the out-plane resistivity is lower. The tree-like columnar structure exhibits poor in- and out-plane conductivity properties, whereas pillar-like and dense TiO2 exhibits similar in- and out-plane conductivities even if their morphologies are noticeably different

Modified impact of emotion on temporal discrimination in a transgenic rat model of Huntington disease

Huntington\u27s disease (HD) is characterized by triad of motor, cognitive, and emotional symptoms along with neuropathology in fronto-striatal circuit and limbic system including amygdala. Emotional alterations, which have a negative impact on patient well-being, represent some of the earliest symptoms of HD and might be related to the onset of the neurodegenerative process. In the transgenic rat model (tgHD rats), evidence suggest emotional alterations at the symptomatic stage along with neuropathology of the central nucleus of amygdala (CE). Studies in humans and animals demonstrate that emotion can modulate time perception. The impact of emotion on time perception has never been tested in HD, nor is it known if that impact could be part of the presymptomatic emotional phenotype of the pathology. The aim of this paper was to characterize the effect of emotion on temporal discrimination in presymptomatic tgHD animals. In the first experiment, we characterized the acute effect of an emotion (fear) conditioned stimulus on temporal discrimination using a bisection procedure, and tested its dependency upon an intact central amygdala. The second experiment was aimed at comparing presymptomatic homozygous transgenic animals at 7-months of age and their wild-type littermates (WT) in their performance on the modulation of temporal discrimination by emotion. Our principal findings show that (1) a fear cue produces a short-lived decrease of temporal precision after its termination, and (2) animals with medial CE lesion and presymptomatic tgHD animals demonstrate an alteration of this emotion-evoked temporal distortion. The results contribute to our knowledge about the presymptomatic phenotype of this HD rat model, showing susceptibility to emotion that may be related to dysfunction of the central nucleus of amygdala