Beta-catenin/TCF4 transactivates miR-30e during intestinal cell differentiation

The Wnt/beta-catenin/TCF4 pathway plays critical roles in the maintenance of small intestinal epithelium; however, downstream targets of the beta-catenin/TCF4 complex are not extensively characterized. We identified miR-30e as an immediate target activated by the beta-catenin/TCF4 complex. miR-30e was detected in the peri-nuclear region of the intestinal crypt IEC-6 cells. Bioinformatics analysis revealed clustered beta-catenin/TCF4 binding sites within the miR-30e promoter region. This promoter region was cloned into pGL3-control luciferase reporter vector, with the enhancer region removed. Transfection of pCMV-SPORT6-beta-catenin expression vector dose-dependently increased luciferase activity, and co-transfection of pCMV-SPORT6-TCF4 expression vector further enhanced the promoter activity. Dexamethasone-induced IEC-6 cells differentiation caused a 2.5-fold increase in miR-30e expression, and upon beta-catenin siRNA transfection, miR-30e increased 1.3-fold. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay confirmed the binding between beta-catenin/TCF4 complexes from IEC-6 nuclear extracts and the putative sequences in the miR-30e promoter. These results demonstrate that beta-catenin/TCF4 transactivates miR-30e during intestinal cell differentiation

Finding the engram.

Many attempts have been made to localize the physical trace of a memory, or engram, in the brain. However, until recently, engrams have remained largely elusive. In this Review, we develop four defining criteria that enable us to critically assess the recent progress that has been made towards finding the engram. Recent \u27capture\u27 studies use novel approaches to tag populations of neurons that are active during memory encoding, thereby allowing these engram-associated neurons to be manipulated at later times. We propose that findings from these capture studies represent considerable progress in allowing us to observe, erase and express the engram

Ubiquitous molecular substrates for associative learning and activity-dependent neuronal facilitation.

Recent evidence suggests that many of the molecular cascades and substrates that contribute to learning-related forms of neuronal plasticity may be conserved across ostensibly disparate model systems. Notably, the facilitation of neuronal excitability and synaptic transmission that contribute to associative learning in Aplysia and Hermissenda, as well as associative LTP in hippocampal CA1 cells, all require (or are enhanced by) the convergence of a transient elevation in intracellular Ca2+ with transmitter binding to metabotropic cell-surface receptors. This temporal convergence of Ca2+ and G-protein-stimulated second-messenger cascades synergistically stimulates several classes of serine/threonine protein kinases, which in turn modulate receptor function or cell excitability through the phosphorylation of ion channels. We present a summary of the biophysical and molecular constituents of neuronal and synaptic facilitation in each of these three model systems. Although specific components of the underlying molecular cascades differ across these three systems, fundamental aspects of these cascades are widely conserved, leading to the conclusion that the conceptual semblance of these superficially disparate systems is far greater than is generally acknowledged. We suggest that the elucidation of mechanistic similarities between different systems will ultimately fulfill the goal of the model systems approach, that is, the description of critical and ubiquitous features of neuronal and synaptic events that contribute to memory induction

Production of dust by massive stars at high redshift

The large amounts of dust detected in sub-millimeter galaxies and quasars at high redshift pose a challenge to galaxy formation models and theories of cosmic dust formation. At z > 6 only stars of relatively high mass (> 3 Msun) are sufficiently short-lived to be potential stellar sources of dust. This review is devoted to identifying and quantifying the most important stellar channels of rapid dust formation. We ascertain the dust production efficiency of stars in the mass range 3-40 Msun using both observed and theoretical dust yields of evolved massive stars and supernovae (SNe) and provide analytical expressions for the dust production efficiencies in various scenarios. We also address the strong sensitivity of the total dust productivity to the initial mass function. From simple considerations, we find that, in the early Universe, high-mass (> 3 Msun) asymptotic giant branch stars can only be dominant dust producers if SNe generate <~ 3 x 10^-3 Msun of dust whereas SNe prevail if they are more efficient. We address the challenges in inferring dust masses and star-formation rates from observations of high-redshift galaxies. We conclude that significant SN dust production at high redshift is likely required to reproduce current dust mass estimates, possibly coupled with rapid dust grain growth in the interstellar medium.Comment: 72 pages, 9 figures, 5 tables; to be published in The Astronomy and Astrophysics Revie

The genetic architecture of sexually selected traits in two natural populations of Drosophila montana

The work was supported by the National Environment Research Council (grant NE/E015255/1 to MGR and RKB) and the Academy of Finland (project 132619 to AH).We investigated the genetic architecture of courtship song and cuticular hydrocarbon traits in two phygenetically distinct populations of Drosophila montana. To study natural variation in these two important traits, we analysed within-population crosses among individuals sampled from the wild. Hence, the genetic variation analysed should represent that available for natural and sexual selection to act upon. In contrast to previous between-population crosses in this species, no major quantitative trait loci (QTLs) were detected, perhaps because the between-population QTLs were due to fixed differences between the populations. Partitioning the trait variation to chromosomes suggested a broadly polygenic genetic architecture of within-population variation, although some chromosomes explained more variation in one population compared with the other. Studies of natural variation provide an important contrast to crosses between species or divergent lines, but our analysis highlights recent concerns that segregating variation within populations for important quantitative ecological traits may largely consist of small effect alleles, difficult to detect with studies of moderate power.PostprintPeer reviewe

Off-axis neutral beam current drive for advanced scenario development in DIII-D

Modification of the two existing DIII-D neutral beamlines is planned to allow vertical steering to provide off-axis neutral beam current drive (NBCD) peaked as far off-axis as half the plasma minor radius. New calculations for a downward-steered beam indicate strong current drive with good localization off-axis so long as the toroidal magnetic field, B , and the plasma current, I , point in the same direction. This is due to good alignment of neutral beam injection (NBI) with the local pitch of the magnetic field lines. This model has been tested experimentally on DIII-D by injecting equatorially mounted NBs into reduced size plasmas that are vertically displaced with respect to the vessel midplane. The existence of off-axis NBCD is evident in the changes seen in sawtooth behaviour in the internal inductance. By shifting the plasma upwards or downwards, or by changing the sign of the toroidal field, off-axis NBCD profiles measured with motional Stark effect data and internal loop voltage show a difference in amplitude (40-45%) consistent with differences predicted by the changed NBI alignment with respect to the helicity of the magnetic field lines. The effects of NBI direction relative to field line helicity can be large even in ITER: off-axis NBCD can be increased by more than 30% if the B direction is reversed. Modification of the DIII-D NB system will strongly support scenario development for ITER and future tokamaks as well as provide flexible scientific tools for understanding transport, energetic particles and heating and current drive. © 2009 IAEA, Vienna. T p

Off-axis neutral beam current drive for advanced scenario development in DIII-D

Modification of the two existing DIII-D neutral beamlines is planned to allow vertical steering to provide off-axis neutral beam current drive (NBCD) peaked as far off-axis as half the plasma minor radius. New calculations for a downward-steered beam indicate strong current drive with good localization off-axis so long as the toroidal magnetic field, BT, and the plasma current, Ip, point in the same direction. This is due to good alignment of neutral beam injection (NBI) with the local pitch of the magnetic field lines. This model has been tested experimentally on DIII-D by injecting equatorially mounted NBs into reduced size plasmas that are vertically displaced with respect to the vessel midplane. The existence of off-axis NBCD is evident in the changes seen in sawtooth behaviour in the internal inductance. By shifting the plasma upwards or downwards, or by changing the sign of the toroidal field, off-axis NBCD profiles measured with motional Stark effect data and internal loop voltage show a difference in amplitude (40-45%) consistent with differences predicted by the changed NBI alignment with respect to the helicity of the magnetic field lines. The effects of NBI direction relative to field line helicity can be large even in ITER: off-axis NBCD can be increased by more than 30% if the BT direction is reversed. Modification of the DIII-D NB system will strongly support scenario development for ITER and future tokamaks as well as provide flexible scientific tools for understanding transport, energetic particles and heating and current drive. © 2009 IAEA, Vienna