Conditional expression in corticothalamic efferents reveals a developmental role for nicotinic acetylcholine receptors in modulation of passive avoidance behavior

Prenatal nicotine exposure has been linked to attention deficit hyperactivity disorder and cognitive impairment, but the sites of action for these effects of nicotine are still under investigation. High-affinity nicotinic acetylcholine receptors (nAChRs) contain the .2 subunit and modulate passive avoidance (PA) learning in mice. Using an inducible, tetracycline-regulated transgenic system, we generated lines of mice with expression of high-affinity nicotinic receptors restored in specific neuronal populations. One line of mice shows functional .2 subunit-containing nAChRs localized exclusively in corticothalamic efferents. Functional, presynaptic nAChRs are present in the thalamus of these mice as detected by nicotine-elicited rubidium efflux assays from synaptosomes. Knock-out mice lacking high-affinity nAChRs show elevated baseline PA learning, whereas normal baseline PA behavior is restored in mice with corticothalamic expression of these nAChRs. In contrast, nicotine can enhance PA learning in adult wild-type animals but not in corticothalamic-expressing transgenic mice. When these transgenic mice are treated with doxycycline in adulthood to switch off nAChR expression, baseline PA is maintained even after transgene expression is abolished. These data suggest that high-affinity nAChRs expressed on corticothalamic neurons during development are critical for baseline PA performance and provide a potential neuroanatomical substrate for changes induced by prenatal nicotine exposure leading to long-term behavioral and cognitive deficits

High-Contrast NIR Polarization Imaging of MWC480

One of the key predictions of modeling from the IR excess of Herbig Ae stars is that for protoplanetary disks, where significant grain growth and settling has occurred, the dust disk has flattened to the point that it can be partially or largely shadowed by the innermost material at or near the dust sublimation radius. When the self-shadowing has already started, the outer disk is expected to be detected in scattered light only in the exceptional cases that the scale height of the dust disk at the sublimation radius is smaller than usual. High-contrast imaging combined with the IR spectral energy distribution allow us to measure the degree of flattening of the disk, as well as to determine the properties of the outer disk. We present polarimetric differential imaging in $H$ band obtained with Subaru/HiCIAO of one such system, MWC 480. The HiCIAO data were obtained at a historic minimum of the NIR excess. The disk is detected in scattered light from 0\farcs2-1\farcs0 (27.4-137AU). Together with the marginal detection of the disk from 1998 February 24 by HST/NICMOS, our data constrain the opening half angle for the disk to lie between 1.3$\leq\theta\leq 2.2^\circ$. When compared with similar measures in CO for the gas disk from the literature, the dust disk subtends only $\sim$30% of the gas disk scale height (H/R$\sim$0.03). Such a dust disk is a factor of 5-7 flatter than transitional disks, which have structural signatures that giant planets have formed.Comment: 21 pages, 6 figures, 1 table, ApJ accepted 2012-05-0

Observations of Past Lunar Landing Sites by the D-CIXS X-Ray Spectrometer on SMART-1

D-CIXS initial observations show a first unambiguous remote sensing of calcium in the lunar regolith. Data obtained are broadly consistent with current understanding of mare and highland composition. Ground truth is provided by the returned Apollo and Luna sample sets

Iterative graph cuts for image segmentation with a nonlinear statistical shape prior

Shape-based regularization has proven to be a useful method for delineating objects within noisy images where one has prior knowledge of the shape of the targeted object. When a collection of possible shapes is available, the specification of a shape prior using kernel density estimation is a natural technique. Unfortunately, energy functionals arising from kernel density estimation are of a form that makes them impossible to directly minimize using efficient optimization algorithms such as graph cuts. Our main contribution is to show how one may recast the energy functional into a form that is minimizable iteratively and efficiently using graph cuts.Comment: Revision submitted to JMIV (02/24/13

Dopamine D_2-receptor activation elicits akinesia, rigidity, catalepsy, and tremor in mice expressing hypersensitive 4 nicotinic receptors via a cholinergic-dependent mechanism

Recent studies suggest that high-affinity neuronal nicotinic acetylcholine receptors (nAChRs) containing α4 and β2 subunits (α4β2*) functionally interact with G-protein-coupled dopamine (DA) D_2 receptors in basal ganglia. We hypothesized that if a functional interaction between these receptors exists, then mice expressing an M2 point mutation (Leu9'Ala) rendering 4 nAChRs hypersensitive to ACh may exhibit altered sensitivity to a D_2-receptor agonist. When challenged with the D_(2)R agonist, quinpirole (0.5–10 mg/kg), Leu9'Ala mice, but not wild-type (WT) littermates, developed severe, reversible motor impairment characterized by rigidity, catalepsy, akinesia, and tremor. While striatal DA tissue content, baseline release, and quinpirole-induced DA depletion did not differ between Leu9'Ala and WT mice, quinpirole dramatically increased activity of cholinergic striatal interneurons only in mutant animals, as measured by increased c-Fos expression in choline acetyltransferase (ChAT)-positive interneurons. Highlighting the importance of the cholinergic system in this mouse model, inhibiting the effects of ACh by blocking muscarinic receptors, or by selectively activating hypersensitive nAChRs with nicotine, rescued motor symptoms. This novel mouse model mimics the imbalance between striatal DA/ACh function associated with severe motor impairment in disorders such as Parkinson’s disease, and the data suggest that a D_(2)R–α4*-nAChR functional interaction regulates cholinergic interneuron activity.—Zhao-Shea, R., Cohen, B. N., Just, H., McClure-Begley, T., Whiteaker, P., Grady, S. R., Salminen, O., Gardner, P. D., Lester, H. A., Tapper, A. R. Dopamine D2-receptor activation elicits akinesia, rigidity, catalepsy, and tremor in mice expressing hypersensitive α4 nicotinic receptors via a cholinergic-dependent mechanism

The origin of hydrogen line emission for five Herbig Ae/Be stars spatially resolved by VLTI/AMBER spectro-interferometry

To trace the accretion and outflow processes around YSOs, diagnostic spectral lines such as the BrG 2.166 micron line are widely used, although due to a lack of spatial resolution, the origin of the line emission is still unclear. Employing the AU-scale spatial resolution which can be achieved with infrared long-baseline interferometry, we aim to distinguish between theoretical models which associate the BrG line emission with mass infall or mass outflow processes. Using the VLTI/AMBER instrument, we spatially and spectrally (R=1500) resolved the inner environment of five Herbig Ae/Be stars (HD163296, HD104237, HD98922, MWC297, V921Sco) in the BrG emission line as well as in the adjacent continuum. All objects (except MWC297) show an increase of visibility within the BrG emission line, indicating that the BrG-emitting region in these objects is more compact than the dust sublimation radius. For HD98922, our quantitative analysis reveals that the line-emitting region is compact enough to be consistent with the magnetospheric accretion scenario. For HD163296, HD104237, MWC297, and V921Sco we identify a stellar wind or a disk wind as the most likely line-emitting mechanism. We search for general trends and find that the size of the BrG-emitting region does not seem to depend on the basic stellar parameters, but correlates with the H-alpha line profile shape. We find evidence for at least two distinct BrG line-formation mechanisms. Stars with a P-Cygni H-alpha line profile and a high mass-accretion rate seem to show particularly compact BrG-emitting regions (R_BrG/R_cont<0.2), while stars with a double-peaked or single-peaked H-alpha-line profile show a significantly more extended BrG-emitting region (0.6<R_BrG/R_cont<1.4), possibly tracing a stellar wind or a disk wind.Comment: 20 pages; 11 figures; Accepted by A&A; a high quality version of the paper can be obtained at http://www.skraus.eu/papers/kraus.HAeBe-BrGsurvey.pd

Integrated microfluidic tmRNA purification and real-time NASBA device for molecular diagnostics.

We demonstrate the first integrated microfluidic tmRNA purification and nucleic acid sequence-based amplification (NASBA) device incorporating real-time detection. The real-time amplification and detection step produces pathogen-specific response in < 3 min from the chip-purified RNA from 100 lysed bacteria. On-chip RNA purification uses a new silica bead immobilization method. On-chip amplification uses custom-designed high-selectivity primers and real-time detection uses molecular beacon fluorescent probe technology; both are integrated on-chip with NASBA. Present in all bacteria, tmRNA (10Sa RNA) includes organism-specific identification sequences, exhibits unusually high stability relative to mRNA, and has high copy number per organism; the latter two factors improve the limit of detection, accelerate time-to-positive response, and suit this approach ideally to the detection of small numbers of bacteria. Device efficacy was demonstrated by integrated on-chip purification, amplification, and real-time detection of 100 E. coli bacteria in 100 microL of crude lysate in under 30 min for the entire process