Synapse-specific expression of calcium-permeable AMPA receptors in neocortical layer 5

In the hippocampus, calcium‐permeable AMPA receptors have been found in a restricted subset of neuronal types that inhibit other neurons, although their localization in the neocortex is less well understood. In the present study, we looked for calcium‐permeable AMPA receptors in two distinct populations of neocortical inhibitory neurons: basket cells and Martinotti cells. We found them in the former but not in the latter. Furthermore, in basket cells, these receptors were associated with particularly fast responses. Computer modelling predicted (and experiments verified) that fast calcium‐permeable AMPA receptors enable basket cells to respond rapidly, such that they promptly inhibit neighbouring cells and shut down activity. The results obtained in the present study help our understanding of pathologies such as stroke and epilepsy that have been associated with disordered regulation of calcium‐permeable AMPA receptors

Recognition memory, self-other source memory, and theory-of-mind in children with autism spectrum disorder.

This study investigated semantic and episodic memory in autism spectrum disorder (ASD), using a task which assessed recognition and self-other source memory. Children with ASD showed undiminished recognition memory but significantly diminished source memory, relative to age- and verbal ability-matched comparison children. Both children with and without ASD showed an “enactment effect”, demonstrating significantly better recognition and source memory for self-performed actions than other-person-performed actions. Within the comparison group, theory-of-mind (ToM) task performance was significantly correlated with source memory, specifically for other-person-performed actions (after statistically controlling for verbal ability). Within the ASD group, ToM task performance was not significantly correlated with source memory (after controlling for verbal ability). Possible explanations for these relations between source memory and ToM are considered

Fluctuation Study of the Specific Heat of MgB2

The specific heat of polycrystalline Mg$^{11}$B$_{2}$ has been measured with high resolution ac calorimetry from 5 to 45 K at constant magnetic fields. The excess specific heat above T$_{c}$ is discussed in terms of Gaussian fluctuations and suggests that Mg$^{11}$B$_{2}$ is a bulk superconductor with Ginzburg-Landau coherence length $\xi_{0}=26$ \AA . The transition-width broadening in field is treated in terms of lowest-Landau-level (LLL) fluctuations. That analysis requires that $\xi_{0}=20$ \AA . The underestimate of the coherence length in field, along with deviations from 3D LLL predictions, suggest that there is an influence from the anisotropy of B$_{c2}$ between the c-axis and the a-b plane.Comment: Phys. Rev. B 66, 134515 (2002

Dexamethasone Treatment Induces the Reprogramming of Pancreatic Acinar Cells to Hepatocytes and Ductal Cells

The pancreatic exocrine cell line AR42J-B13 can be reprogrammed to hepatocytes following treatment with dexamethasone. The question arises whether dexamethasone also has the capacity to induce ductal cells as well as hepatocytes.AR42J-B13 cells were treated with and without dexamethasone and analyzed for the expression of pancreatic exocrine, hepatocyte and ductal markers. Addition of dexamethasone inhibited pancreatic amylase expression, induced expression of the hepatocyte marker transferrin as well as markers typical of ductal cells: cytokeratin 7 and 19 and the lectin peanut agglutinin. However, the number of ductal cells was low compared to hepatocytes. The proportion of ductal cells was enhanced by culture with dexamethasone and epidermal growth factor (EGF). We established several features of the mechanism underlying the transdifferentiation of pancreatic exocrine cells to ductal cells. Using a CK19 promoter reporter, we show that a proportion of the ductal cells arise from differentiated pancreatic exocrine-like cells. We also examined whether C/EBPβ (a transcription factor important in the conversion of pancreatic cells to hepatocytes) could alter the conversion from acinar cells to a ductal phenotype. Overexpression of an activated form of C/EBPβ in dexamethasone/EGF-treated cells provoked the expression of hepatocyte markers and inhibited the expression of ductal markers. Conversely, ectopic expression of a dominant-negative form of C/EBPβ, liver inhibitory protein, inhibited hepatocyte formation in dexamethasone-treated cultures and enhanced the ductal phenotype.These results indicate that hepatocytes and ductal cells may be induced from pancreatic exocrine AR42J-B13 cells following treatment with dexamethasone. The conversion from pancreatic to hepatocyte or ductal cells is dependent upon the expression of C/EBPβ

Numerical studies of the phase diagram of layered type II superconductors in a magnetic field

We report on simulations of layered superconductors using the Lawrence-Doniach model in the framework of the lowest Landau level approximation. We find a first order phase transition with a $B(T)$ dependence which agrees very well with the experimental ``melting'' line in YBaCuO. The transition is not associated with vortex lattice melting, but separates two vortex liquid states characterised by different degrees of short-range crystalline order and different length scales of correlations between vortices in different layers. The transition line ends at a critical end-point at low fields. We find the magnetization discontinuity and the location of the lower critical magnetic field to be in good agreement with experiments in YBaCuO. Length scales of order parameter correlations parallel and perpendicular to the magnetic field increase exponentially as 1/T at low temperatures. The dominant relaxation time scales grow roughly exponentially with these correlation lengths. We find that the first order phase transition persists in the presence of weak random point disorder but can be suppressed entirely by strong disorder. No vortex glass or Bragg glass state is found in the presence of disorder. The consistency of our numerical results with various experimental features in YBaCuO, including the dependence on anisotropy, and the temperature dependence of the structure factor at the Bragg peaks in neutron scattering experiments is demonstrated.Comment: 25 pages (revtex), 19 figures included, submitted to PR

Flux Lattice Melting and Lowest Landau Level Fluctuations

We discuss the influence of lowest Landau level (LLL) fluctuations near H_{c2}(T) on flux lattice melting in YBa$_2$Cu$_3$O$_{7-\delta}$ (YBCO). We show that the specific heat step of the flux lattice melting transition in YBCO single crystals can be attributed largely to the degrees of freedom associated with LLL fluctuations. These degrees of freedom have already been shown to account for most of the latent heat. We also show that these results are a consequence of the correspondence between flux lattice melting and the onset of LLL fluctuations.Comment: 4 pages, 2 embedded figure

Evolutionary Mechanisms of Long-Term Genome Diversification Associated With Niche Partitioning in Marine Picocyanobacteria.

Marine picocyanobacteria of the genera Prochlorococcus and Synechococcus are the most abundant photosynthetic organisms on Earth, an ecological success thought to be linked to the differential partitioning of distinct ecotypes into specific ecological niches. However, the underlying processes that governed the diversification of these microorganisms and the appearance of niche-related phenotypic traits are just starting to be elucidated. Here, by comparing 81 genomes, including 34 new Synechococcus, we explored the evolutionary processes that shaped the genomic diversity of picocyanobacteria. Time-calibration of a core-protein tree showed that gene gain/loss occurred at an unexpectedly low rate between the different lineages, with for instance 5.6 genes gained per million years (My) for the major Synechococcus lineage (sub-cluster 5.1), among which only 0.71/My have been fixed in the long term. Gene content comparisons revealed a number of candidates involved in nutrient adaptation, a large proportion of which are located in genomic islands shared between either closely or more distantly related strains, as identified using an original network construction approach. Interestingly, strains representative of the different ecotypes co-occurring in phosphorus-depleted waters (Synechococcus clades III, WPC1, and sub-cluster 5.3) were shown to display different adaptation strategies to this limitation. In contrast, we found few genes potentially involved in adaptation to temperature when comparing cold and warm thermotypes. Indeed, comparison of core protein sequences highlighted variants specific to cold thermotypes, notably involved in carotenoid biosynthesis and the oxidative stress response, revealing that long-term adaptation to thermal niches relies on amino acid substitutions rather than on gene content variation. Altogether, this study not only deciphers the respective roles of gene gains/losses and sequence variation but also uncovers numerous gene candidates likely involved in niche partitioning of two key members of the marine phytoplankton

Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid.

Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5-20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of D-glucose was lower than D-fructose. However, uptake of D-glucose was higher than D-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection