Keck Echellette Spectrograph and Imager Observations of Metal-poor Damped Lyα Systems

We present the first results from a survey of SDSS quasars selected for strong H I damped Lyα (DLA) absorption with corresponding low equivalent width absorption from strong low-ion transitions (e.g., C II λ1334 and Si II λ1260). These metal-poor DLA candidates were selected from the SDSS fifth release quasar spectroscopic database, and comprise a large new sample for probing low-metallicity galaxies. Medium-resolution echellette spectra from the Keck Echellette Spectrograph and Imager spectrograph for an initial sample of 35 systems were obtained to explore the metal-poor tail of the DLA distribution and to investigate the nucleosynthetic patterns at these metallicities. We have estimated saturation corrections for the moderately underresolved spectra, and systems with very narrow Doppler parameters (b ≤ 5 km s^(–1)) will likely have underestimated abundances. For those systems with Doppler parameters b > 5 km s^(–1), we have measured low-metallicity DLA gas with [X/H] < –2.4 for at least one of C, O, Si, or Fe. Assuming non-saturated components, we estimate that several DLA systems have [X/H] < –2.8, including five DLA systems with both low equivalent widths and low metallicity in transitions of both C II and O I. All of the measured DLA metallicities, however, exceed or are consistent with a metallicity of at least 1/1000 of solar, regardless of the effects of saturation in our spectra. Our results indicate that the metal-poor tail of galaxies at z ~ 3 drops exponentially at [X/H] ≾ –3. If the distribution of metallicity is Gaussian, the probability of identifying interstellar medium gas with lower abundance is extremely small, and our results suggest that DLA systems with [X/H] < –4.0 are extremely rare, and could comprise only 8 × 10^(–7) of DLA systems. The relative abundances of species within these low-metallicity DLA systems are compared with stellar nucleosynthesis models, and are consistent with stars having masses of 30 M_⊙ < M * < 100 M_⊙. The observed ratio of [C/O] for values of [O/H] < –2.5 exceeds values seen in moderate metallicity DLA systems, and also exceeds theoretical nucleosynthesis predictions for higher mass Population III stars. We also have observed a correlation between the column density N(C IV) with [Si/H] metallicity, suggestive of a trend between mass of the DLA system and its metallicity

Constraints on Circumstellar Material around the Type Ia Supernova 2007af

Patat et al. recently inferred the existence of circumstellar material around a normal Type Ia supernova (SN Ia) for the first time, finding time-variable Na I D absorption lines in the spectrum of SN 2006X. We present high-resolution spectroscopy of the bright SN Ia 2007af at three epochs and search for variability in any of the Na D absorption components. Over the time range from 4 days before to 24 days after maximum light, we find that the host-galaxy Na D lines appear to be of interstellar rather than circumstellar origin and do not vary down to the level of 18 mÅ (column density of 2 × 10^(11) cm^(-2)). We limit any circumstellar absorption lines to be weaker than ~10 mÅ (6 × 10^(10) cm^(-2)). For the case of material distributed in spherically symmetric shells of radius ~10^(16) cm surrounding the progenitor system, we place an upper limit on the shell mass of ~(3 × 10^(-8))/X M_⊙, where X is the Na ionization fraction. We also show that SN 2007af is a photometrically and spectroscopically normal SN Ia. Assuming that the variable Na D lines in SN 2006X came from circumstellar matter, we therefore conclude that either there is a preferred geometry for the detection of variable absorption components in SNe Ia, or SN 2007af and SN 2006X had different types of progenitor systems

Genome-Wide Transcriptional Response to Varying RpoS Levels in Escherichia coli K-12

The alternative sigma factor RpoS is a central regulator of many stress responses in Escherichia coli. The level of functional RpoS differs depending on the stress. The effect of these differing concentrations of RpoS on global transcriptional responses remains unclear. We investigated the effect of RpoS concentration on the transcriptome during stationary phase in rich media. We found that 23% of genes in the E. coli genome are regulated by RpoS, and we identified many RpoS-transcribed genes and promoters. We observed three distinct classes of response to RpoS by genes in the regulon: genes whose expression changes linearly with increasing RpoS level, genes whose expression changes dramatically with the production of only a little RpoS (“sensitive” genes), and genes whose expression changes very little with the production of a little RpoS (“insensitive”). We show that sequences outside the core promoter region determine whether an RpoS-regulated gene is sensitive or insensitive. Moreover, we show that sensitive and insensitive genes are enriched for specific functional classes and that the sensitivity of a gene to RpoS corresponds to the timing of induction as cells enter stationary phase. Thus, promoter sensitivity to RpoS is a mechanism to coordinate specific cellular processes with growth phase and may also contribute to the diversity of stress responses directed by RpoS

Unitary Ca2+ current through recombinant type 3 InsP3 receptor channels under physiological ionic conditions

The ubiquitous inositol 1,4,5-trisphosphate (InsP3) receptor (InsP3R) channel, localized primarily in the endoplasmic reticulum (ER) membrane, releases Ca2+ into the cytoplasm upon binding InsP3, generating and modulating intracellular Ca2+ signals that regulate numerous physiological processes. Together with the number of channels activated and the open probability of the active channels, the size of the unitary Ca2+ current (iCa) passing through an open InsP3R channel determines the amount of Ca2+ released from the ER store, and thus the amplitude and the spatial and temporal nature of Ca2+ signals generated in response to extracellular stimuli. Despite its significance, iCa for InsP3R channels in physiological ionic conditions has not been directly measured. Here, we report the first measurement of iCa through an InsP3R channel in its native membrane environment under physiological ionic conditions. Nuclear patch clamp electrophysiology with rapid perfusion solution exchanges was used to study the conductance properties of recombinant homotetrameric rat type 3 InsP3R channels. Within physiological ranges of free Ca2+ concentrations in the ER lumen ([Ca2+]ER), free cytoplasmic [Ca2+] ([Ca2+]i), and symmetric free [Mg2+] ([Mg2+]f), the iCa–[Ca2+]ER relation was linear, with no detectable dependence on [Mg2+]f. iCa was 0.15 ± 0.01 pA for a filled ER store with 500 µM [Ca2+]ER. The iCa–[Ca2+]ER relation suggests that Ca2+ released by an InsP3R channel raises [Ca2+]i near the open channel to ∼13–70 µM, depending on [Ca2+]ER. These measurements have implications for the activities of nearby InsP3-liganded InsP3R channels, and they confirm that Ca2+ released by an open InsP3R channel is sufficient to activate neighboring channels at appropriate distances away, promoting Ca2+-induced Ca2+ release

Previous Exposure to Δ9-Tetrahydrocannibinol Enhances Locomotor Responding to but Not Self-Administration of AmphetamineS⃞

Previous exposure to amphetamine leads to enhanced locomotor and nucleus accumbens (NAcc) dopamine (DA) responding to the drug as well as enhanced amphetamine self-administration. Here, we investigated the effects of exposure to Δ9-tetrahydrocannibinol (Δ9-THC) on behavioral and biochemical responding to amphetamine. Rats in different groups received five exposure injections of vehicle or one of five doses of Δ9-THC (0.4, 0.75, 1.5, 3.0, and 6.0 mg/kg i.p.) and were tested 2 days and 2 weeks later. Exposure to all but the lowest and highest doses of Δ9-THC enhanced the locomotor response to amphetamine (0.75 mg/kg i.p.), but all failed to enhance NAcc DA overflow in response to the drug. Moreover, exposure to 3.0 mg/kg i.p. Δ9-THC increased forskolin-evoked adenylyl cyclase activity in the NAcc and rats' locomotor response to the direct DA receptor agonist apomorphine (1.0 mg/kg s.c.), suggesting that Δ9-THC sensitized locomotor responding to amphetamine by up-regulating postsynaptic DA receptor signaling in the NAcc. Finally, amphetamine self-administration (200 μg/kg/infusion i.v.) was enhanced in amphetamine (5 × 1.5 mg/kg i.p.)-exposed rats, but not in rats exposed to Δ9-THC (5 × 3.0 mg/kg i.p.). Previous exposure to this dose of Δ9-THC modestly increased apomorphine SA (0.5 mg/kg/infusion i.v.). Thus, unlike amphetamine exposure, exposure to Δ9-THC does not enhance the subsequent NAcc DA response to amphetamine or promote amphetamine self-administration. Although Δ9-THC leads to alterations in postsynaptic DA receptor signaling in the NAcc and these can affect the generation of locomotion, these neuroadaptations do not seem to be linked to the expression of enhanced amphetamine self-administration

A Role for Dopamine-Mediated Learning in the Pathophysiology and Treatment of Parkinson’s Disease

Dopamine contributes to corticostriatal plasticity and motor learning. Dopamine denervation profoundly alters motor performance, as in Parkinson’s disease (PD); however, the extent to which these symptoms reflect impaired motor learning is unknown. Here, we demonstrate a D2 receptor blockade-induced aberrant learning that impedes future motor performance when dopamine signaling is restored, an effect diminished by coadministration of adenosine antagonists during blockade. We hypothesize that an inappropriate corticostriatal potentiation in striatopallidal cells of the indirect pathway underlies aberrant learning. We demonstrate synaptic potentiation in striatopallidal neurons induced by D2 blockade and diminished by application of an adenosine antagonist, consistent with behavioral observations. A neurocomputational model of the basal ganglia recapitulates the behavioral pattern and further links aberrant learning to plasticity in the indirect pathway. Thus, D2-mediated aberrant learning may contribute to motor deficits in PD, suggesting new avenues for the development of therapeutics