Inducible gene inactivation in neurons of the adult mouse forebrain

<p>Abstract</p> <p>Background</p> <p>The analysis of the role of genes in important brain functions like learning, memory and synaptic plasticity requires gene inactivation at the adult stage to exclude developmental effects, adaptive changes or even lethality. In order to achieve temporally controlled somatic mutagenesis, the Cre/loxP-recombination system has been complemented with the tamoxifen-inducible fusion protein consisting of Cre recombinase and the mutated ligand binding domain of the human estrogen receptor (CreER^T2). To induce recombination of conditional alleles in neurons of the adult forebrain, we generated a bacterial artificial chromosome-derived transgene expressing the CreER^T2fusion protein under control of the regulatory elements of the CaMKIIα gene (CaMKCreER^T2transgene).</p> <p>Results</p> <p>We established three mouse lines harboring one, two and four copies of the CaMKCreER^T2transgene. The CaMKCreER^T2transgene displayed reliable and copy number-dependent expression of Cre recombinase specifically in neurons of the adult forebrain. Using Cre reporter mice we show very low background activity of the transgene in absence of the ligand and efficient induction of recombination upon tamoxifen treatment in all three lines. In addition, we demonstrate in mice harboring two conditional glucocorticoid receptor (GR) alleles and the CaMKCreER^T2transgene spatially restricted loss of GR protein expression in neurons of the adult forebrain upon tamoxifen treatment.</p> <p>Conclusion</p> <p>This is to our knowledge the first approach allowing highly efficient inducible gene inactivation in neurons of the adult mouse forebrain. This new approach will be a useful tool to dissect the function of specific genes in the adult forebrain. Effects of gene inactivation on pre- and postnatal brain development and compensatory mechanisms elicited by an early onset of gene inactivation can now be excluded.</p

Compatibility of Gauss maps with metrics

We give necessary and sufficient conditions on a smooth local map of a Riemannian manifold $M^m$ into the sphere $S^m$ to be the Gauss map of an isometric immersion $u:M^m \to R^n$, $n=m+1$. We briefly discuss the case of general $n$ as wellComment: 14 pages, no figure

Enzymatic hydrolysis of kaempferol 3-O-(2‴-O-sinapoyl-β-sophoroside), the key bitter compound of rapeseed (Brassica napus L.) protein isolate

BACKGROUND: The use of rapeseed protein for human nutrition is primarily limited by its strong bitterness, which is why the key bitter compound, kaempferol 3-O-(2‴-O-sinapoyl-β-sophoroside), is enzymatically degraded. RESULTS: Mass spectrometry analyses of an extract from an untreated rapeseed protein isolate gave three signals for m/z 815 [M-H]. The predominant compound among the three compounds was confirmed as kaempferol-3-O-(2‴-O-sinapoyl-β-sophoroside). Enzymatic hydrolysis of this key bitter compound was achieved using a sinapyl ester cleaving side activity of a ferulic acid esterase (FAE) from the basidiomycete Schizophyllum commune (ScoFAE). Recombinant ferulic acid esterases from Streptomyces werraensis (SwFAE) and from Pleurotus eryngii (PeFAE) possessed better cleavage activity towards methyl sinapate but did not hydrolyze the sinapyl ester linkage of the bitter kaempferol sophoroside. CONCLUSION: Kaempferol-3-O-(2‴-O-sinapoyl-β-sophoroside) was successfully degraded by enzymatic treatment with ScoFAE, which may provide a means to move the status of rapeseed protein from feed additive to food ingredient. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry

Mineralocorticoid receptor is essential for corticosteroid-induced up-regulation of L-type calcium currents in cultured neonatal cardiomyocytes

Despite the fact that mineralocorticoid receptor (MR) antagonist drugs such as spironolactone and eplerenone reduce the mortality in heart failure patients, there is, thus far, no unambiguous demonstration of a functional role of MR in cardiac cells. The aim of this work was to investigate the activation pathway(s) mediating corticosteroid-induced up-regulation of cardiac calcium current (I Ca). In this study, using neonatal cardiomyocytes from MR or glucocorticoid receptor (GR) knockout (KO) mice, we show that MR is essential for corticosteroid-induced up-regulation of I Ca. This study provides the first direct and unequivocal evidence for MR function in the hear

The enigmatic young brown dwarf binary FU Tau: accretion and activity

FU Tau belongs to a rare class of young, wide brown dwarf binaries. We have resolved the system in a Chandra X-ray observation and detected only the primary, FU Tau A. Hard X-ray emission, presumably from a corona, is present but, unexpectedly, we detect also a strong and unusually soft component from FU Tau A. Its X-ray properties, so far unique among brown dwarfs, are very similar to those of the T Tauri star TW Hya. The analogy with TW Hya suggests that the dominating soft X-ray component can be explained by emission from accretion shocks. However, the typical free-fall velocities of a brown dwarf are too low for an interpretation of the observed X-ray temperature as post-shock region. On the other hand, velocities in excess of the free-fall speed are derived from archival optical spectroscopy, and independent pieces of evidence for strong accretion in FU Tau A are found in optical photometry. The high X-ray luminosity of FU Tau A coincides with a high bolometric luminosity confirming an unexplained trend among young brown dwarfs. In fact, FU Tau A is overluminous with respect to evolutionary models while FU Tau B is on the 1 Myr isochrone suggesting non-contemporaneous formation of the two components in the binary. The extreme youth of FU Tau A could be responsible for its peculiar X-ray properties, in terms of atypical magnetic activity or accretion. Alternatively, rotation and magnetic field effects may reduce the efficiency of convection which in turn affects the effective temperature and radius of FU Tau A shifting its position in the HR diagram. Although there is no direct prove of this latter scenario so far we present arguments for its plausibility.Comment: Accepted for publication in MNRAS; 9 pages, 5 figure

Design and implementation of an illumination system to mimic skyglow at ecosystem level in a large-scale lake enclosure facility

Light pollution is an environmental stressor of global extent that is growing exponentially in area and intensity. Artificial skyglow, a form of light pollution with large range, is hypothesized to have environmental impact at ecosystem level. However, testing the impact of skyglow at large scales and in a controlled fashion under in situ conditions has remained elusive so far. Here we present the first experimental setup to mimic skyglow at ecosystem level outdoors in an aquatic environment. Spatially diffuse and homogeneous surface illumination that is adjustable between 0.01 and 10 lx, resembling rural to urban skyglow levels, was achieved with white light-emitting diodes at a large-scale lake enclosure facility. The illumination system was enabled by optical modeling with Monte-Carlo raytracing and validated by measurements. Our method can be adapted to other outdoor and indoor skyglow experiments, urgently needed to understand the impact of skyglow on ecosystems

Discovery potential of top-partners in a realistic composite Higgs model with early LHC data

Composite Higgs models provide a natural, non-supersymmetric solution to the hierarchy problem. In these models, one or more sets of heavy top-partners are typically introduced. Some of these new quarks can be relatively light, with a mass of a few hundred GeV, and could be observed with the early LHC collision data expected to be collected during 2010. We analyse in detail the collider signatures that these new quarks can produce. We show that final states with two (same-sign) or three leptons are the most promising discovery channels. They can yield a 5 sigma excess over the Standard Model expectation already with the 2010 LHC collision data. Exotic quarks of charge 5/3 are a distinctive feature of this model. We present a new method to reconstruct their masses from their leptonic decay without relying on jets in the final state.Comment: 28 pages 11 Figures 7 Tables, minor changes, added references, matches published versio

Isoscalar dipole coherence at low energies and forbidden E1 strength

In 16O and 40Ca an isoscalar, low-energy dipole transition (IS-LED) exhausting approximately 4% of the isoscalar dipole (ISD) energy-weighted sum rule is experimentally known, but conspicuously absent from recent theoretical investigations of ISD strength. The IS-LED mode coincides with the so-called isospin-forbidden E1 transition. We report that for N=Z nuclei up to 100Sn the fully self-consistent Random-Phase-Approximation with finite-range forces, phenomenological and realistic, yields a collective IS-LED mode, typically overestimating its excitation energy, but correctly describing its IS strength and electroexcitation form factor. The presence of E1 strength is solely due to the Coulomb interaction between the protons and the resulting isospin-symmetry breaking. The smallness of its value is related to the form of the transition density, due to translational invariance. The calculated values of E1 and ISD strength carried by the IS-LED depend on the effective interaction used. Attention is drawn to the possibility that in N-not-equal-Z nuclei this distinct mode of IS surface vibration can develop as such or mix strongly with skin modes and thus influence the pygmy dipole strength as well as the ISD strength function. In general, theoretical models currently in use may be unfit to predict its precise position and strength, if at all its existence.Comment: 9 pages, 6 figures, EPJA submitte

Investigation on shape deviation of horizontal interior circular channels fabricated by laser powder bed fusion

The fabrication of horizontal interior circular channels poses some unique challenges to the laser powder bed fusion (L-PBF) process. The engineering challenge is to be able to print horizontal interior channels using L-PBF without using support structures, while the scientific challenge is to predict the shape deviation in the horizontal channel. This paper studies the geometric fidelity (roundness and shape deviation) of L-PBF printed horizontal interior circular channels (diameters 1−3 mm) by developing experiment-based regression models and a preliminary computational fluid dynamics (CFD) simulation model. The roundness error is found to be affected by the shape/size of the melt pool, thermal stresses, beam offset, and the slicing algorithm. It is recommended that to decrease the roundness error, in addition to choosing a proper beam offset, the width/depth of the melt pool should be minimized by minimizing the volumetric energy density (smaller laser power or higher scanning speed). Shape deviation in overhanging structures is determined by the thermo-mechanical driven molten flow in the melt pool. Hanging structures with irregular profiles (dross) are formed due to the sinking of the melt pool on an unconsolidated powder bed under the effect of gravity, surface tension, and poor thermal conductivity. (Partially) unmelted powder randomly adheres to the edges of the melt pool enlarging the hanging structure and roughening the profile. Small laser power or large scanning speed benefits reducing the roundness error and hang-diameter ratio. 0° or 45° rotational linear scanning strategy can be selected for minimizing the roundness error or the hang-diameter ratio, respectively