Cocaine but Not Natural Reward Self-Administration nor Passive Cocaine Infusion Produces Persistent LTP in the VTA

SummaryPersistent drug-seeking behavior is hypothesized to co-opt the brain's natural reward-motivational system. Although ventral tegmental area (VTA) dopamine (DA) neurons represent a crucial component of this system, the synaptic adaptations underlying natural rewards and drug-related motivation have not been fully elucidated. Here, we show that self-administration of cocaine, but not passive cocaine infusions, produced a persistent potentiation of VTA excitatory synapses, which was still present after 3 months abstinence. Further, enhanced synaptic function in VTA was evident even after 3 weeks of extinction training. Food or sucrose self-administration induced only a transient potentiation of VTA glutamatergic signaling. Our data show that synaptic function in VTA DA neurons is readily but reversibly enhanced by natural reward-seeking behavior, while voluntary cocaine self-administration induced a persistent synaptic enhancement that is resistant to behavioral extinction. Such persistent synaptic potentiation in VTA DA neurons may represent a fundamental cellular phenomenon driving pathological drug-seeking behavior

Dating the Cryptococcus gattii Dispersal to the North American Pacific Northwest.

The emergence of Cryptococcus gattii, previously regarded as a predominantly tropical pathogen, in the temperate climate of the North American Pacific Northwest (PNW) in 1999 prompted several questions. The most prevalent among these was the timing of the introduction of this pathogen to this novel environment. Here, we infer tip-dated timing estimates for the three clonal C. gattii populations observed in the PNW, VGIIa, VGIIb, and VGIIc, based on whole-genome sequencing of 134 C. gattii isolates and using Bayesian evolutionary analysis by sampling trees (BEAST). We estimated the nucleotide substitution rate for each lineage (1.59 × 10-8, 1.59 × 10-8, and 2.70 × 10-8, respectively) to be an order of magnitude higher than common neutral fungal mutation rates (2.0 × 10-9), indicating a microevolutionary rate (e.g., successive clonal generations in a laboratory) in comparison to a species' slower, macroevolutionary rate (e.g., when using fossil records). The clonal nature of the PNW C. gattii emergence over a narrow number of years would therefore possibly explain our higher mutation rates. Our results suggest that the mean time to most recent common ancestor for all three sublineages occurred within the last 60 to 100 years. While the cause of C. gattii dispersal to the PNW is still unclear, our research estimates that the arrival is neither ancient nor very recent (i.e., <25 years ago), making a strong case for an anthropogenic introduction. IMPORTANCE The recent emergence of the pathogenic fungus Cryptococcus gattii in the Pacific Northwest (PNW) resulted in numerous investigations into the epidemiological and enzootic impacts, as well as multiple genomic explorations of the three primary molecular subtypes of the fungus that were discovered. These studies lead to the general conclusion that the subtypes identified likely emerged out of Brazil. Here, we conducted genomic dating analyses to determine the ages of the various lineages seen in the PNW and propose hypothetical causes for the dispersal events. Bayesian evolutionary analysis strongly suggests that these independent fungal populations in the PNW are all 60 to 100 years old, providing a timing that is subsequent to the opening of the Panama Canal, which allowed for more direct shipping between Brazil and the western North American coastline, a possible driving event for these fungal translocation events

Cooling of Dense Gas by H2O Line Emission and an Assessment of its Effects in Chondrule-Forming Shocks

We consider gas at densities appropriate to protoplanetary disks and calculate its ability to cool due to line radiation emitted by H2O molecules within the gas. Our work follows that of Neufeld & Kaufman (1993; ApJ, 418, 263), expanding on their work in several key aspects, including use of a much expanded line database, an improved escape probability formulism, and the inclusion of dust grains, which can absorb line photons. Although the escape probabilities formally depend on a complicated combination of optical depth in the lines and in the dust grains, we show that the cooling rate including dust is well approximated by the dust-free cooling rate multiplied by a simple function of the dust optical depth. We apply the resultant cooling rate of a dust-gas mixture to the case of a solar nebula shock pertinent to the formation of chondrules, millimeter-sized melt droplets found in meteorites. Our aim is to assess whether line cooling can be neglected in chondrule-forming shocks or if it must be included. We find that for typical parameters, H2O line cooling shuts off a few minutes past the shock front; line photons that might otherwise escape the shocked region and cool the gas will be absorbed by dust grains. During the first minute or so past the shock, however, line photons will cool the gas at rates ~ 10,000 K/hr, dropping the temperature of the gas (and most likely the chondrules within the gas) by several hundred K. Inclusion of H2O line cooling therefore must be included in models of chondrule formation by nebular shocks.Comment: Accepted for publication in The Astrophysical Journa

Reduced Nucleus Accumbens SK Channel Activity Enhances Alcohol Seeking during Abstinence

SummaryThe cellular mechanisms underlying pathological alcohol seeking remain poorly understood. Here, we show an enhancement of nucleus accumbens (NAcb) core action potential firing ex vivo after protracted abstinence from alcohol but not sucrose self-administration. Increased firing is associated with reduced small-conductance calcium-activated potassium channel (SK) currents and decreased SK3 but not SK2 subunit protein expression. Furthermore, SK activation ex vivo produces greater firing suppression in NAcb core neurons from alcohol- versus sucrose-abstinent rats. Accordingly, SK activation in the NAcb core significantly reduces alcohol but not sucrose seeking after abstinence. In contrast, NAcb shell and lateral dorsal striatal firing ex vivo are not altered after abstinence from alcohol, and SK activation in these regions has little effect on alcohol seeking. Thus, decreased NAcb core SK currents and increased excitability represents a critical mechanism that facilitates motivation to seek alcohol after abstinence

Large-Scale Bioinformatics Analysis of Bacillus Genomes Uncovers Conserved Roles of Natural Products in Bacterial Physiology

ABSTRACT Bacteria possess an amazing capacity to synthesize a diverse range of structurally complex, bioactive natural products known as specialized (or secondary) metabolites. Many of these specialized metabolites are used as clinical therapeutics, while others have important ecological roles in microbial communities. The biosynthetic gene clusters (BGCs) that generate these metabolites can be identified in bacterial genome sequences using their highly conserved genetic features. We analyzed an unprecedented 1,566 bacterial genomes from Bacillus species and identified nearly 20,000 BGCs. By comparing these BGCs to one another as well as a curated set of known specialized metabolite BGCs, we discovered that the majority of Bacillus natural products are comprised of a small set of highly conserved, well-distributed, known natural product compounds. Most of these metabolites have important roles influencing the physiology and development of Bacillus species. We identified, in addition to these characterized compounds, many unique, weakly conserved BGCs scattered across the genus that are predicted to encode unknown natural products. Many of these “singleton” BGCs appear to have been acquired via horizontal gene transfer. Based on this large-scale characterization of metabolite production in the Bacilli , we go on to connect the alkylpyrones, natural products that are highly conserved but previously biologically uncharacterized, to a role in Bacillus physiology: inhibiting spore development. IMPORTANCE Bacilli are capable of producing a diverse array of specialized metabolites, many of which have gained attention for their roles as signals that affect bacterial physiology and development. Up to this point, however, the Bacillus genus’s metabolic capacity has been underexplored. We undertook a deep genomic analysis of 1,566 Bacillus genomes to understand the full spectrum of metabolites that this bacterial group can make. We discovered that the majority of the specialized metabolites produced by Bacillus species are highly conserved, known compounds with important signaling roles in the physiology and development of this bacterium. Additionally, there is significant unique biosynthetic machinery distributed across the genus that might lead to new, unknown metabolites with diverse biological functions. Inspired by the findings of our genomic analysis, we speculate that the highly conserved alkylpyrones might have an important biological activity within this genus. We go on to validate this prediction by demonstrating that these natural products are developmental signals in Bacillus and act by inhibiting sporulation

Beyond the Bandwagon: Curating Cultural Memory at Milner Library

Archival and manuscript materials record human experience; they document how people have lived, worked, interacted, and thought about the world. These unique or rare materials make visible the experience and impact of individuals and organizations within their respective cultural, geographical, historical, local, and educational milieu. By exploring such documents and objects, patrons can see and investigate these relationships firsthand. Primary sources form the bedrock of humanistic research, personal inquiry, and engaged teaching. With this volume, we invite you to explore the unique and rare materials housed in Milner Library’s Special Collections and Dr. Jo Ann Rayfield University Archives as well as the services that bring them to life for readers worldwide. Contributed essays from scholars and collection stewards highlight how a small sample of these rich collections facilitate teaching and learning within the Illinois State University community and beyond.https://ir.library.illinoisstate.edu/mlp/1032/thumbnail.jp

Challenging Hazards Amidst Observational Simulation in the Emergency Department: Advancing Gamification in Simulation Education Through a Novel Resident-led Skills Competition.

Medical simulation competitions have become an increasingly popular method to provide a hands-on gamified approach to education and training in the health professions. The most well-known competition, SimWars, consists of well-coordinated teams that are tasked with completing a series of mind-bending clinical scenarios in front of a live audience through \u27bracket-style\u27 elimination rounds. Similarly, challenging hazards amidst observational simulation (CHAOS) in the emergency department (ED) is another novel approach to gamification in both its structure and feel. Conducted at the Council of Emergency Medicine Resident Directors (CORD) 2018 National Assembly in San Antonio, Texas, instead of assigning premeditated teams, it placed random Emergency Medicine (EM) faculty, residents, and medical students together in teams to test them on a variety of fundamental EM content areas. Additionally, the event incorporated multiple levels within each round, allowing the inclusion of additional information to be shared with participants to support switching gears, as is typical for teams working in the ED and augmenting the perceived level of chaos. To assess this pilot project, formal quantitative and qualitative feedback was solicited at the end of the session. Quantitative evaluation of the intervention was obtained through an eight-item questionnaire using a five-point Likert-type scale from 19 of the 20 enrolled participants (95% response rate). Responses were generally positive with an overall course rating score of 4.45 out of 5 (SD +/- 0.62). Qualitative feedback revealed that learners enjoyed performing procedures and networking with their EM colleagues. The majority of residents (95%) recommend the activity be integrated into subsequent conferences. Areas for improvement included shorter cases and minimizing technical malfunctions. CHAOS in the ED was a successful pilot study that incorporated gamification as a means to deploy simulation-based training at a national emergency medicine conference in a community of simulation educators. Future studies should focus on incorporating learners\u27 feedback into subsequent CHAOS iterations and reducing overhead costs to increase its adoption by both regional and national audiences

HerMES: SPIRE Science Demonstration Phase maps

We describe the production and verification of sky maps of the five Spectral and Photometric Imaging Receiver (SPIRE) fields observed as part of the Herschel Multi-tiered Extragalactic Survey (HerMES) during the Science Demonstration Phase (SDP) of the Herschel mission. We have implemented an iterative map-making algorithm [The SPIRE-HerMES Iterative Mapper (SHIM)] to produce high fidelity maps that preserve extended diffuse emission on the sky while exploiting the repeated observations of the same region of the sky with many detectors in multiple scan directions to minimize residual instrument noise. We specify here the SHIM algorithm and outline the various tests that were performed to determine and characterize the quality of the maps and verify that the astrometry, point source flux and power on all relevant angular scales meet the needs of the HerMES science goals. These include multiple jackknife tests, determination of the map transfer function and detailed examination of the power spectra of both sky and jackknife maps. The map transfer function is approximately unity on scales from 1 arcmin to 1°. Final maps (v1.0), including multiple jackknives, as well as the SHIM pipeline, have been used by the HerMES team for the production of SDP papers

MALT90 Kinematic Distances to Dense Molecular Clumps

Using molecular-line data from the Millimetre Astronomy Legacy Team 90 GHz Survey (MALT90), we have estimated kinematic distances to 1905 molecular clumps identified in the ATLASGAL 870 μm continuum survey over the longitude range 295° < l < 350°. The clump velocities were determined using a flux-weighted average of the velocities obtained from Gaussian fits to the HCO+, HNC, and N2H+ (1–0) transitions. The near/far kinematic distance ambiguity was addressed by searching for the presence or absence of absorption or self-absorption features in 21 cm atomic hydrogen spectra from the Southern Galactic Plane Survey. Our algorithm provides an estimation of the reliability of the ambiguity resolution. The Galactic distribution of the clumps indicates positions where the clumps are bunched together, and these locations probably trace the locations of spiral arms. Several clumps fall at the predicted location of the far side of the Scutum–Centaurus arm. Moreover, a number of clumps with positive radial velocities are unambiguously located on the far side of the Milky Way at galactocentric radii beyond the solar circle. The measurement of these kinematic distances, in combination with continuum or molecular-line data, now enables the determination of fundamental parameters such as mass, size, and luminosity for each clump

Gravitational Waves From Known Pulsars: Results From The Initial Detector Era

We present the results of searches for gravitational waves from a large selection of pulsars using data from the most recent science runs (S6, VSR2 and VSR4) of the initial generation of interferometric gravitational wave detectors LIGO (Laser Interferometric Gravitational-wave Observatory) and Virgo. We do not see evidence for gravitational wave emission from any of the targeted sources but produce upper limits on the emission amplitude. We highlight the results from seven young pulsars with large spin-down luminosities. We reach within a factor of five of the canonical spin-down limit for all seven of these, whilst for the Crab and Vela pulsars we further surpass their spin-down limits. We present new or updated limits for 172 other pulsars (including both young and millisecond pulsars). Now that the detectors are undergoing major upgrades, and, for completeness, we bring together all of the most up-to-date results from all pulsars searched for during the operations of the first-generation LIGO, Virgo and GEO600 detectors. This gives a total of 195 pulsars including the most recent results described in this paper.United States National Science FoundationScience and Technology Facilities Council of the United KingdomMax-Planck-SocietyState of Niedersachsen/GermanyAustralian Research CouncilInternational Science Linkages program of the Commonwealth of AustraliaCouncil of Scientific and Industrial Research of IndiaIstituto Nazionale di Fisica Nucleare of ItalySpanish Ministerio de Economia y CompetitividadConselleria d'Economia Hisenda i Innovacio of the Govern de les Illes BalearsNetherlands Organisation for Scientific ResearchPolish Ministry of Science and Higher EducationFOCUS Programme of Foundation for Polish ScienceRoyal SocietyScottish Funding CouncilScottish Universities Physics AllianceNational Aeronautics and Space AdministrationOTKA of HungaryLyon Institute of Origins (LIO)National Research Foundation of KoreaIndustry CanadaProvince of Ontario through the Ministry of Economic Development and InnovationNational Science and Engineering Research Council CanadaCarnegie TrustLeverhulme TrustDavid and Lucile Packard FoundationResearch CorporationAlfred P. Sloan FoundationAstronom