Kv4 potassium channels modulate hippocampal EPSP-spike potentiation and spatial memory in rats

International audienceKv4 channels regulate the backpropagation of action potentials (b-AP) and have been implicated in the modulation of longterm potentiation (LTP). Here we showed that blockade of Kv4 channels by the scorpion toxin AmmTX3 impaired reference memory in a radial maze task. In vivo, AmmTX3 intracerebroventricular (i.c.v.) infusion increased and stabilized the EPSP-spike (E-S) component of LTP in the dentate gyrus (DG), with no effect on basal transmission or short-term plasticity. This increase in E-S potentiation duration could result from the combination of an increase in excitability of DG granular cells with a reduction of GABAergic inhibition, leading to a strong reduction of input specificity. Radioactive in situ hybridization (ISH) was used to evaluate the amounts of Kv4.2 and Kv4.3 mRNA in brain structures at different stages of a spatial learning task in naive, pseudoconditioned, and conditioned rats. Significant differences in Kv4.2 and Kv4.3 mRNA levels were observed between conditioned and pseudoconditioned rats. Kv4.2 and Kv4.3 mRNA levels were transiently up-regulated in the striatum, nucleus accumbens, retrosplenial, and cingulate cortices during early stages of learning, suggesting an involvement in the switch from egocentric to allocentric strategies. Spatial learning performance was positively correlated with the levels of Kv4.2 and Kv4.3 mRNAs in several of these brain structures. Altogether our findings suggestthat Kv4 channels could increase the signal-to-noise ratio during information acquisition, thereby allowing a better encoding of the memory trace

Characterisation of adipocyte-derived extracellular vesicle subtypes identifies distinct protein and lipid signatures for large and small extracellular vesicles

Extracellular vesicles (EVs) are biological vectors that can modulate the metabolism of target cells by conveying signalling proteins and genomic material. The level of EVs in plasma is significantly increased in cardiometabolic diseases associated with obesity, suggesting their possible participation in the development of metabolic dysfunction. With regard to the poor definition of adipocyte-derived EVs, the purpose of this study was to characterise both qualitatively and quantitatively EVs subpopulations secreted by fat cells. Adipocyte-derived EVs were isolated by differential centrifugation of conditioned media collected from 3T3-L1 adipocytes cultured for 24 h in serum-free conditions. Based on morphological and biochemical properties, as well as quantification of secreted EVs, we distinguished two subpopulations of adipocyte-derived EVs, namely small extracellular vesicles (sEVs) and large extracellular vesicles (lEVs). Proteomic analyses revealed that lEVs and sEVs exhibit specific protein signatures, allowing us not only to define novel markers of each population, but also to predict their biological functions. Despite similar phospholipid patterns, the comparative lipidomic analysis performed on these EV subclasses revealed a specific cholesterol enrichment of the sEV population, whereas lEVs were characterised by high amounts of externalised phosphatidylserine. Enhanced secretion of lEVs and sEVs is achievable following exposure to different biological stimuli related to the chronic low-grade inflammation state associated with obesity. Finally, we demonstrate the ability of primary murine adipocytes to secrete sEVs and lEVs, which display physical and biological characteristics similar to those described for 3T3-L1. Our study provides additional information and elements to define EV subtypes based on the characterisation of adipocyte-derived EV populations. It also underscores the need to distinguish EV subpopulations, through a combination of multiple approaches and markers, since their specific composition may cause distinct metabolic responses in recipient cells and tissues

Programmable disorder in random DNA tilings

Scaling up the complexity and diversity of synthetic molecular structures will require strategies that exploit the inherent stochasticity of molecular systems in a controlled fashion. Here we demonstrate a framework for programming random DNA tilings and show how to control the properties of global patterns through simple, local rules. We constructed three general forms of planar network—random loops, mazes and trees—on the surface of self-assembled DNA origami arrays on the micrometre scale with nanometre resolution. Using simple molecular building blocks and robust experimental conditions, we demonstrate control of a wide range of properties of the random networks, including the branching rules, the growth directions, the proximity between adjacent networks and the size distribution. Much as combinatorial approaches for generating random one-dimensional chains of polymers have been used to revolutionize chemical synthesis and the selection of functional nucleic acids, our strategy extends these principles to random two-dimensional networks of molecules and creates new opportunities for fabricating more complex molecular devices that are organized by DNA nanostructures

Experimental Evolution of a Plant Pathogen into a Legume Symbiont

Following acquisition of a rhizobial symbiotic plasmid, adaptive mutations in the virulence pathway allowed pathogenic Ralstonia solanacearum to evolve into a legume symbiont under plant selection

Validation of a Multi-Purpose Depletion Chain for Burnup Calculation through TRIPOLI-4 Calculations and IFP Perturbation Method

International audienceThe current standard depletion chain used by the CEA, called CEA-V5, was validated to treat only LWRs in 2008. This single depletion chain must correctly model the global loss of reactivity for both LWRs and Fast Reactors for future APOLLO3 work on Generation III and IV reactors such as EPR and ASTRID projects milestones. In order to verify the loss of reactivity of the standard CEA-V5 chain, a reference chain with 885 Fission Products (FPs) has been defined and used with the French Monte Carlo code TRIPOLI-4 and its depletion module for comparisons with the standard CEA-V5 chain containing 126 FPs. Three test cases are modeled, a UOX PWR cell, a MOX PWR cell and a MOX SFR cell, to validate the standard chain against the reference one. Results obtained from TRIPOLI-4 can then be used to calculate a loss of reactivity for each case to verify that the standard chain takes into account the majority (ideally 99.9%) of the anti-reactivity of the reference chain. In addition, this loss of reactivity has been decomposed by isotope to rank the FPs by importance using the Iterated Fission Probability (IFP) method recently implemented in TRIPOLI-4

In vitro effects of lactoferrin on intestinal and mammary epithelial cell lines

Lactoferrin is an iron binding glycoprotein endowed with multiple functions, including non-specific immune defence against pathogens, immunomodulatory activity and regulation of cell growth. The gastrointestinal tract of the newborn and the mammary gland are targets of the biological action of lactoferrin. This work aimed at examining the effects of human and bovine lactoferrin on cell growth using intestinal and mammary epithelial cell lines and at evaluating the protective effect of bovine lactoferrin against cytotoxic damage induced by bacterial lipopolysaccharides in a bovine mammary epithelial cell line. It was shown that lactoferrin could be involved in regulating the growth of both intestinal and mammary epithelial cells depending on its concentrations, cell culture conditions and cell line used. The presence of lactoferrin binding sites on the cell surface was also discussed. Moreover, the data obtained suggested that bovine lactoferrin could contribute to counteract the effect of bacterial endotoxins

The endoplasmic reticulum and casein-containing vesicles contribute to milk fat globule membrane

During lactation, mammary epithelial cells secrete huge amounts of milk from their apical side. The current view is that caseins are secreted by exocytosis, whereas milk fat globules are released by budding, enwrapped by the plasma membrane. Owing to the number and large size of milk fat globules, the membrane surface needed for their release might exceed that of the apical plasma membrane. A large-scale proteomics analysis of both cytoplasmic lipid droplets and secreted milk fat globule membranes was used to decipher the cellular origins of the milk fat globule membrane. Surprisingly, differential analysis of protein profiles of these two organelles strongly suggest that, in addition to the plasma membrane, the endoplasmic reticulum and the secretory vesicles contribute to the milk fat globule membrane. Analysis of membrane-associated and raft microdomain proteins reinforces this possibility and also points to a role for lipid rafts in milk product secretion. Our results provide evidence for a significant contribution of the endoplasmic reticulum to the milk fat globule membrane and a role for SNAREs in membrane dynamics during milk secretion. These novel aspects point to a more complex model for milk secretion than currently envisioned