Behavioral and neuroanatomical consequences of cell-type specific loss of dopamine D2 receptors in the mouse cerebral cortex

Developmental dysregulation of dopamine D2 receptors (D2Rs) alters neuronal migration, differentiation, and behavior and contributes to the psychopathology of neurological and psychiatric disorders. The current study is aimed at identifying how cell-specific loss of D2Rs in the cerebral cortex may impact neurobehavioral and cellular development, in order to better understand the roles of this receptor in cortical circuit formation and brain disorders. We deleted D2R from developing cortical GABAergic interneurons (Nkx2.1-Cre) or from developing telencephalic glutamatergic neurons (Emx1-Cre). Conditional knockouts (cKO) from both lines, Drd2fl/fl, Nkx2.1-Cre+ (referred to as GABA-D2R-cKO mice) or Drd2fl/fl, Emx1-Cre+ (referred to as Glu-D2R-cKO mice), exhibited no differences in simple tests of anxiety-related or depression-related behaviors, or spatial or nonspatial working memory. Both GABA-D2R-cKO and Glu-D2R-cKO mice also had normal basal locomotor activity, but GABA-D2R-cKO mice expressed blunted locomotor responses to the psychotomimetic drug MK-801. GABA-D2R-cKO mice exhibited improved motor coordination on a rotarod whereas Glu-D2R-cKO mice were normal. GABA-D2R-cKO mice also exhibited spatial learning deficits without changes in reversal learning on a Barnes maze. At the cellular level, we observed an increase in PV+ cells in the frontal cortex of GABA-D2R-cKO mice and no noticeable changes in Glu-D2R-cKO mice. These data point toward unique and distinct roles for D2Rs within excitatory and inhibitory neurons in the regulation of behavior and interneuron development, and suggest that location-biased D2R pharmacology may be clinically advantageous to achieve higher efficacy and help avoid unwanted effects.Fil: Lee, Gloria S.. Florida State University; Estados UnidosFil: Graham, Devon L.. Florida State University; Estados UnidosFil: Noble, Brenda L.. Florida State University; Estados UnidosFil: Trammell, Taylor S.. Florida State University; Estados UnidosFil: McCarthy, Deirdre M.. Florida State University; Estados UnidosFil: Anderson, Lisa R.. Florida State University; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Bhide, Pradeep G.. Florida State University; Estados UnidosFil: Stanwood, Gregg D.. Florida State University; Estados Unido

HST NICMOS Observations of the Polarization of NGC 1068

We have observed the polarized light at 2 micron in the center of NGC 1068 with HST NICMOS Camera 2. The nucleus is dominated by a bright, unresolved source, polarized at a level of 6.0 pm 1.2% with a position angle of 122degr pm 1.5degr. There are two polarized lobes extending up to 8'' northeast and southwest of the nucleus. The polarized flux in both lobes is quite clumpy, with the maximum polarization occurring in the southwest lobe at a level of 17% when smoothed to 0.23'' resolution. The perpendiculars to the polarization vectors in these two lobes point back to the intense unresolved nuclear source to within one 0.076'' Camera 2 pixel, thereby confirming that this is the illuminating source of the scattered light and therefore the probable AGN central engine. Whereas the polarization of the nucleus is probably caused by dichroic absorption, the polarization in the lobes is almost certainly caused by scattering, with very little contribution from dichroic absorption. Features in the polarized lobes include a gap at a distance of about 1'' from the nucleus toward the southwest lobe and a ``knot'' of emission about 5'' northeast of the nucleus. Both features had been discussed by ground-based observers, but they are much better defined with the high spatial resolution of NICMOS. The northeast knot may be the side of a molecular cloud that is facing the nucleus, which cloud may be preventing the expansion of the northeast radio lobe at the head of the radio synchrotron-radiation-emitting jet. We also report the presence of two ghosts in the Camera 2 polarizers. These had not been detected previously (Hines et al. 2000) because they are relatively faint and require observations of a source with a large dynamic range.Comment: 17 pages, 4 figure

Coronavirus infection and PARP expression dysregulate the NAD metabolome: An actionable component of innate immunity

Poly(ADP-ribose) polymerase (PARP) superfamily members covalently link either a single ADP-ribose (ADPR) or a chain of ADPR units to proteins using NAD as the source of ADPR. Although the well-known poly(ADP-ribosylating) (PARylating) PARPs primarily function in the DNA damage response, many noncanonical mono(ADP-ribosylating) (MARylating) PARPs are associated with cellular antiviral responses. We recently demonstrated robust up-regulation of several PARPs following infection with murine hepatitis virus (MHV), a model coronavirus. Here we show that SARS-CoV-2 infection strikingly up-regulates MARylating PARPs and induces the expression of genes encoding enzymes for salvage NAD synthesis from nicotinamide (NAM) and nicotinamide riboside (NR), while down-regulating other NAD biosynthetic pathways. We show that overexpression of PARP10 is sufficient to depress cellular NAD and that the activities of the transcriptionally induced enzymes PARP7, PARP10, PARP12 and PARP14 are limited by cellular NAD and can be enhanced by pharmacological activation of NAD synthesis. We further demonstrate that infection with MHV induces a severe attack on host cell NAD+ and NADP+. Finally, we show that NAMPT activation, NAM, and NR dramatically decrease the replication of an MHV that is sensitive to PARP activity. These data suggest that the antiviral activities of noncanonical PARP isozyme activities are limited by the availability of NAD and that nutritional and pharmacological interventions to enhance NAD levels may boost innate immunity to coronaviruses

Resonant X-Ray Scattering from CeB6_{6}

We calculate the resonant x-ray scattering (RXS) spectra near the Ce $L_{\rm III}$ absorption edge in CeB$_6$, on the basis of a microscopic model that the $4f$ states of Ce are atomic while the $5d$ states form an energy band with a reasonable density of states. In the initial state, we employ an effective Hamiltonian of Shiina {\it et al}. in the antiferro-quadrupole (AFQ) ordering phase, while we construct the wave function consistent with the neutron scattering experiment in the magnetic ground state. In the intermediate state, we take full account of the intra-atomic Coulomb interaction. Without assuming any lattice distortion, we obtain sufficient RXS intensities on the AFQ superlattice spot. We obtain the spectral shape, the temperature and magnetic field dependences in good agreement with the experiment, thus demonstrating the mechanism that the intensity is brought about by the modulation of $5d$ states through the anisotropic term of the $5d$-$4f$ Coulomb interaction. In the magnetic ground state, a small pre-edge peak is found by the $E_2$ process. On the magnetic superlattice spot, we get a finite but considerably small intensity. The magnetic form factor is briefly discussed.Comment: Latex, 10 pages, 12 figures. To be published in J. Phys. Soc. Jpn., Vol.71, No. 7 (2002

HST Snapshot Survey of Post-AGB Objects

The results from a Hubble Space Telescope (HST) snapshot survey of post-AGB objects are shown. The aim of the survey is to complement existing HST images of PPN and to connect various types of nebulosities with physical and chemical properties of their central stars. Nebulosities are detected in 15 of 33 sources. Images and photometric and geometric measurements are presented. For sources with nebulosities we see a morphological bifurcation into two groups, DUPLEX and SOLE, as previous studies have found. We find further support to the previous results suggesting that this dichotomy is caused by a difference in optical thickness of the dust shell. The remaining 18 sources are classified as stellar post-AGB objects, because our observations indicate a lack of nebulosity. We show that some stellar sources may in fact be DUPLEX or SOLE based on their infrared colors. The cause of the differences among the groups are investigated. We discuss some evidence suggesting that high progenitor-mass AGB stars tend to become DUPLEX post-AGB objects. Intermediate progenitor-mass AGB stars tend to be SOLE post-AGB objects. Most of the stellar sources probably have low mass progenitors and do not seem to develop nebulosities during the post-AGB phase and therefore do not become planetary nebulae.Comment: 21 pages, 11 figure

Self-assembled photosystem-I biophotovoltaics on nanostructured TiO2 and ZnO

The abundant pigment-protein membrane complex photosystem-I (PS-I) is at the heart of the Earth’s energy cycle. It is the central molecule in the “Z-scheme” of photosynthesis, converting sunlight into the chemical energy of life. Commandeering this intricately organized photosynthetic nanocircuitry and re-wiring it to produce electricity carries the promise of inexpensive and environmentally friendly solar power. We here report that dry PS-I stabilized by surfactant peptides functioned as both the light-harvester and charge separator in solar cells self-assembled on nanostructured semiconductors. Contrary to previous attempts at biophotovoltaics requiring elaborate surface chemistries, thin film deposition, and illumination concentrated into narrow wavelength ranges the devices described here are straightforward and inexpensive to fabricate and perform well under standard sunlight yielding open circuit photovoltage of 0.5 V, fill factor of 71%, electrical power density of 81 µW/cm2 and photocurrent density of 362 µA/cm2, over four orders of magnitude higher than any photosystem-based biophotovoltaic to date

A first measurement of the interaction cross section of the tau neutrino

The DONuT experiment collected data in 1997 and published first results in 2000 based on four observed $\nu_\tau$ charged-current (CC) interactions. The final analysis of the data collected in the experiment is presented in this paper, based on $3.6 \times 10^{17}$ protons on target using the 800 GeV Tevatron beam at Fermilab. The number of observed $\nu_\tau$ CC interactions is 9, from a total of 578 observed neutrino interactions. We calculated the energy-independent part of the tau-neutrino CC cross section ($\nu + \bar \nu$), relative to the well-known $\nu_e$ and $\nu_\mu$ cross sections. The ratio $\sigma(\nu_\tau)$/$\sigma(\nu_{e,\mu})$ was found to be $1.37\pm0.35\pm0.77$. The $\nu_\tau$ CC cross section was found to be $0.72 \pm 0.24\pm0.36 \times 10^{-38}$ cm$^{2}\rm{GeV}^{-1}$. Both results are in agreement the Standard Model.Comment: 37 pages, 15 figure

PROMPT: Panchromatic Robotic Optical Monitoring and Polarimetry Telescopes

Funded by $1.2M in grants and donations, we are now building PROMPT at CTIO. When completed in late 2005, PROMPT will consist of six 0.41-meter diameter Ritchey-Chrétien telescopes on rapidly slewing mounts that respond to GRB alerts within seconds, when the afterglow is potentially extremely bright. Each mirror and camera coating is being optimized for a different wavelength range and function, including a NIR imager, two red-optimized imagers, a blue-optimized imager, an UV-optimized imager, and an optical polarimeter. PROMPT will be able to identify high-redshift events by dropout and distinguish these events from the similar signatures of extinction. In this way, PROMPT will act as a distance-finder scope for spectroscopic follow up on the larger 4.1-meter diameter SOAR telescope, which is also located at CTIO. When not chasing GRBs, PROMPT serves broader educational objectives across the state of North Carolina. Enclosure construction and the first two telescopes are now complete and functioning: PROMPT observed Swift’s first GRB in December 2004. We upgrade from two to four telescope in February 2005 and from four to six telescopes in mid-2005