351 research outputs found
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Dopamine D3 Receptor Antagonism Reverses the Escalation of Oxycodone Self-administration and Decreases Withdrawal-Induced Hyperalgesia and Irritability-Like Behavior in Oxycodone-Dependent Heterogeneous Stock Rats.
Prescription opioids, such as oxycodone, are highly effective analgesics for clinical pain management, but approximately 25% of patients who are prescribed opioids misuse them, and 5%-10% develop an opioid use disorder (OUD). Effective therapies for the prevention and treatment of opioid abuse and addiction need to be developed. The present study evaluated the effects of the highly selective dopamine D3 receptor antagonist VK4-116 ([R]-N-[4-(4-[3-chloro-5-ethyl-2-methoxyphenyl]piperazin-1-yl)-3-hydroxybutyl]-1H-indole-2-carboxamide) on oxycodone addictive-like behaviors. We used a model of extended access to oxycodone self-administration and tested the effects of VK4-116 on the escalation of oxycodone self-administration and withdrawal-induced hyperalgesia and irritability-like behavior in male and female rats. Pretreatment with VK4-116 (5-25 mg/kg, i.p.) dose-dependently decreased the escalation of oxycodone self-administration and reduced withdrawal-induced hyperalgesia and irritability-like behavior in opioid-dependent rats. These findings demonstrate a key role for D3 receptors in both the motivation to take opioids and negative emotional states that are associated with opioid withdrawal and suggest that D3 receptor antagonism may be a viable therapeutic approach for the treatment of OUD
Data Analysis Recitation Activities Support Better Understanding in SEA-PHAGES CURE
Course-based undergraduate research experiences (CUREs) are widely known to improve student learning outcomes in the sciences. Undergraduate students have a particularly difficult time interpreting the scientific data that they generate in these experiences â especially when lacking opportunity and exposure to science processes prior to entering higher education. Therefore, it is vital to structure these research experiences such that students can see maximal gains in their skills. This is especially true in the SEA-PHAGES (Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science) lab experience, which focuses on bacteriophages â a subject about which most undergraduate students have limited knowledge. In the SEA-PHAGES lab experience at The Ohio State University, we observed that while students made rapid gains in science process skills over the course of the semester, they still struggled to interpret the data they generated. To address this issue, we designed and implemented a set of five recitation activities to complement the lab experience, termed Recitation Activities to Improve Literacy in Science (RAILS). Using an adapted student assessment of learning gains (SALG) survey, we observed that these activities improved students' perceived ability to interpret their data, and students reported that they experienced significant gains in their data analysis ability as a result of the activities. We hope that other SEA-PHAGES instructors will similarly benefit from utilizing these recitation activities as part of their implementation of the curriculum.
Primary image: Phages on RAILS. A bacteriophage is pictured driving a train engine down a track
Differential Gene Expression and Protein Abundance Evince Ontogenetic Bias toward Castes in a Primitively Eusocial Wasp
Polistes paper wasps are models for understanding conditions that may have characterized the origin of worker and queen castes and, therefore, the origin of paper wasp sociality. Polistes is âprimitively eusocialâ by virtue of having context-dependent caste determination and no morphological differences between castes. Even so, Polistes colonies have a temporal pattern in which most female larvae reared by the foundress become workers, and most reared by workers become future-reproductive gynes. This pattern is hypothesized to reflect development onto two pathways, which may utilize mechanisms that regulate diapause in other insects. Using expressed sequence tags (ESTs) for Polistes metricus we selected candidate genes differentially expressed in other insects in three categories: 1) diapause vs. non-diapause phenotypes and/or worker vs. queen differentiation, 2) behavioral subcastes of worker honey bees, and 3) no a priori expectation of a role in worker/gyne development. We also used a non-targeted proteomics screen to test for peptide/protein abundance differences that could reflect larval developmental divergence. We found that foundress-reared larvae (putative worker-destined) and worker-reared larvae (putative gyne-destined) differed in quantitative expression of sixteen genes, twelve of which were associated with caste and/or diapause in other insects, and they also differed in abundance of nine peptides/proteins. Some differentially-expressed genes are involved in diapause regulation in other insects, and other differentially-expressed genes and proteins are involved in the insulin signaling pathway, nutrient metabolism, and caste determination in highly social bees. Differential expression of a gene and a peptide encoding hexameric storage proteins is especially noteworthy. Although not conclusive, our results support hypotheses of 1) larval developmental pathway divergence that can lead to caste bias in adults and 2) nutritional differences as the foundation of the pathway divergence. Finally, the differential expression in Polistes larvae of genes and proteins also differentially expressed during queen vs. worker caste development in honey bees may indicate that regulatory mechanisms of caste outcomes share similarities between primitively eusocial and advanced eusocial Hymenoptera
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The remarkably strong Arctic stratospheric polar vortex of Winter 2020: links to record-breaking arctic oscillation and ozone loss
The Northern Hemisphere (NH) polar winter stratosphere of 2019/2020 featured an exceptionally strong and cold stratospheric polar vortex. Wave activity from the troposphere during DecemberâFebruary was unusually low, which allowed the polar vortex to remain relatively undisturbed. Several transient wave pulses nonetheless served to help create a reflective configuration of the stratospheric circulation by disturbing the vortex in the upper stratosphere. Subsequently, multiple downward wave coupling events took place, which aided in dynamically cooling and strengthening the polar vortex. The persistent strength of the stratospheric polar vortex was accompanied by an unprecedentedly positive phase of the Arctic Oscillation in the troposphere during JanuaryâMarch, which was consistent with large portions of observed surface temperature and precipitation anomalies during the season. Similarly, conditions within the strong polar vortex were ripe for allowing substantial ozone loss: The undisturbed vortex was a strong transport barrier, and temperatures were low enough to form polar stratospheric clouds for over 4âmonths into late March. Total column ozone amounts in the NH polar cap decreased and were the lowest ever observed in the FebruaryâApril period. The unique confluence of conditions and multiple broken records makes the 2019/2020 winter and early spring a particularly extreme example of twoâway coupling between the troposphere and stratosphere
Effects of the nicotinic agonist varenicline, nicotinic antagonist r-bPiDI, and DAT inhibitor R-modafinil on co-use of ethanol and nicotine in female P rats.
Rationale:
Co-users of alcohol and nicotine are the largest group of polysubstance users worldwide. Commonalities in mechanisms of action for ethanol (EtOH) and nicotine proposes the possibility of developing a single pharmacotherapeutic to treat co-use.
Objectives:
Toward developing a preclinical model of co-use, female alcohol-preferring (P) rats were trained for voluntary EtOH drinking and i.v. nicotine self-administration in three phases: (1) EtOH alone (0 vs. 15%, 2-bottle choice); (2) nicotine alone (0.03 mg/kg/infusion, active vs. inactive lever); and (3) concurrent access to both EtOH and nicotine. Using this model, we examined the effects of (1) varenicline, a nicotinic acetylcholine receptor (nAChR) partial agonist with high affinity for the α4ÎČ2 subtype; (2) r-bPiDI, a subtype-selective antagonist at α6ÎČ2* nAChRs; and (3) (R)-modafinil, an atypical inhibitor of the dopamine transporter (DAT).
Results:
In Phases 1 and 2, pharmacologically relevant intake of EtOH and nicotine was achieved. In the concurrent access phase (Phase 3), EtOH consumption decreased while nicotine intake increased relative to Phases 1 and 2. For drug pretreatments, in the EtOH access phase (Phase 1), (R)-modafinil (100 mg/kg) decreased EtOH consumption, with no effect on water consumption. In the concurrent access phase, varenicline (3 mg/kg), r-bPiDI (20 mg/kg), and (R)-modafinil (100 mg/kg) decreased nicotine self-administration, but did not alter EtOH consumption, water consumption, or inactive lever pressing.
Conclusions:
These results indicate that therapeutics which may be useful for smoking cessation via selective inhibition of α4ÎČ2 or α6ÎČ2* nAChRs, or DAT inhibition, may not be sufficient to treat EtOH and nicotine co-use
SDSS-IV MaNGA:the spatially resolved stellar initial mass function in ⌠400 early-type galaxies
MaNGA provides the opportunity to make precise spatially resolved
measurements of the IMF slope in galaxies owing to its unique combination of
spatial resolution, wavelength coverage and sample size. We derive radial
gradients in age, element abundances and IMF slope analysing optical and
near-infrared absorption features from stacked spectra out to the half-light
radius of 366 early-type galaxies with masses .
We find flat gradients in age and [/Fe] ratio, as well as negative
gradients in metallicity, consistent with the literature. We further derive
significant negative gradients in the [Na/Fe] ratio with galaxy centres being
well enhanced in Na abundance by up to 0.5 dex. Finally, we find a gradient in
IMF slope with a bottom-heavy IMF in the centre (typical mass excess factor of
1.5) and a Milky Way-type IMF at the half-light radius. This pattern is
mass-dependent with the lowest mass galaxies in our sample featuring only a
shallow gradient around a Milky Way IMF. Our results imply the local
IMF- relation within galaxies to be even steeper than the global
relation and hint towards the local metallicity being the dominating factor
behind the IMF variations. We also employ different stellar population models
in our analysis and show that a radial IMF gradient is found independently of
the stellar population model used. A similar analysis of the Wing-Ford band
provides inconsistent results and further evidence of the difficulty in
measuring and modelling this particular feature.Comment: 28 pages, 24 figures, 9 tables. MNRAS in pres
SDSS-IV MaNGA: The Spatially Resolved Stellar Initial Mass Function in ~400 Early-Type Galaxies
Mapping Nearby Galaxies at Apache Point Observatory provides the opportunity to make precise spatially resolved measurements of the IMF slope in galaxies owing to its unique combination of spatial resolution, wavelength coverage, and sample size. We derive radial gradients in age, element abundances, and IMF slope analysing optical and near-infrared absorption features from stacked spectra out to the half-light radius of 366 early-type galaxies with masses 9.9â10.8âlogâM/Mâ. We find flat gradients in age and [α/Fe] ratio, as well as negative gradients in metallicity, consistent with the literature. We further derive significant negative gradients in the [Na/Fe] ratio with galaxy centres being well enhanced in Na abundance by up to 0.5 dex. Finally, we find a gradient in IMF slope with a bottom-heavy IMF in the centre (typical mass excess factor of 1.5) and a Milky Way-type IMF at the half-light radius. This pattern is mass dependent with the lowest mass galaxies in our sample featuring only a shallow gradient around a Milky Way IMF. Our results imply the local IMFâÏ relation within galaxies to be even steeper than the global relation and hint towards the local metallicity being the dominating factor behind the IMF variations. We also employ different stellar population models in our analysis and show that a radial IMF gradient is found independently of the stellar population model used. A similar analysis of the Wing-Ford band provides inconsistent results and further evidence of the difficulty in measuring and modelling this particular feature
The Team Keck Treasury Redshift Survey of the GOODS-North Field
We report the results of an extensive imaging and spectroscopic survey in the
GOODS-North field completed using DEIMOS on the Keck II telescope. Observations
of 2018 targets in a magnitude-limited sample of 2911 objects to R=24.4 yield
secure redshifts for a sample of 1440 galaxies and AGN plus 96 stars. In
addition to redshifts and associated quality assessments, our catalog also
includes photometric and astrometric measurements for all targets detected in
our R-band imaging survey of the GOODS-North region. We investigate various
sources of incompleteness and find the redshift catalog to be 53% complete at
its limiting magnitude. The median redshift of z=0.65 is lower than in similar
deep surveys because we did not select against low-redshift targets. Comparison
with other redshift surveys in the same field, including a complementary
Hawaii-led DEIMOS survey, establishes that our velocity uncertainties are as
low as 40 km/s for red galaxies and that our redshift confidence assessments
are accurate. The distributions of rest-frame magnitudes and colors among the
sample agree well with model predictions out to and beyond z=1. We will release
all survey data, including extracted 1-D and sky-subtracted 2-D spectra, thus
providing a sizable and homogeneous database for the GOODS-North field which
will enable studies of large scale structure, spectral indices, internal galaxy
kinematics, and the predictive capabilities of photometric redshifts.Comment: 17 pages, 18 figures, submitted to AJ; v2 minor changes; see survey
database at http://www2.keck.hawaii.edu/realpublic/science/tksurvey
Sympatric woodland Myotis bats form tight-knit social groups with exclusive roost home ranges
Background: The structuring of wild animal populations can influence population dynamics, disease spread, and information transfer. Social network analysis potentially offers insights into these processes but is rarely, if ever, used to investigate more than one species in a community. We therefore compared the social, temporal and spatial networks of sympatric Myotis bats (M. nattereri (Natterer's bats) and M. daubentonii (Daubenton's bats)), and asked: (1) are there long-lasting social associations within species? (2) do the ranges occupied by roosting social groups overlap within or between species? (3) are M. daubentonii bachelor colonies excluded from roosting in areas used by maternity groups?
Results: Using data on 490 ringed M. nattereri and 978 M. daubentonii from 379 colonies, we found that both species formed stable social groups encompassing multiple colonies. M. nattereri formed 11 mixed-sex social groups with few (4.3%) inter-group associations. Approximately half of all M. nattereri were associated with the same individuals when recaptured, with many associations being long-term (>100 days). In contrast, M. daubentonii were sexually segregated; only a quarter of pairs were associated at recapture after a few days, and inter-sex associations were not long-lasting. Social groups of M. nattereri and female M. daubentonii had small roost home ranges (mean 0.2 km2 in each case). Intra-specific overlap was low, but inter-specific overlap was high, suggesting territoriality within but not between species. M. daubentonii bachelor colonies did not appear to be excluded from roosting areas used by females.
Conclusions: Our data suggest marked species- and sex-specific patterns of disease and information transmission are likely between bats of the same genus despite sharing a common habitat. The clear partitioning of the woodland amongst social groups, and their apparent reliance on small patches of habitat for roosting, means that localised woodland management may be more important to bat conservation than previously recognised
LSST Science Book, Version 2.0
A survey that can cover the sky in optical bands over wide fields to faint
magnitudes with a fast cadence will enable many of the exciting science
opportunities of the next decade. The Large Synoptic Survey Telescope (LSST)
will have an effective aperture of 6.7 meters and an imaging camera with field
of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over
20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with
fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a
total point-source depth of r~27.5. The LSST Science Book describes the basic
parameters of the LSST hardware, software, and observing plans. The book
discusses educational and outreach opportunities, then goes on to describe a
broad range of science that LSST will revolutionize: mapping the inner and
outer Solar System, stellar populations in the Milky Way and nearby galaxies,
the structure of the Milky Way disk and halo and other objects in the Local
Volume, transient and variable objects both at low and high redshift, and the
properties of normal and active galaxies at low and high redshift. It then
turns to far-field cosmological topics, exploring properties of supernovae to
z~1, strong and weak lensing, the large-scale distribution of galaxies and
baryon oscillations, and how these different probes may be combined to
constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at
http://www.lsst.org/lsst/sciboo
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