Behavioral Phenotyping of Juvenile Long-Evans and Sprague-Dawley Rats: Implications for Preclinical Models of Autism Spectrum Disorders.

The laboratory rat is emerging as an attractive preclinical animal model of autism spectrum disorder (ASD), allowing investigators to explore genetic, environmental and pharmacological manipulations in a species exhibiting complex, reciprocal social behavior. The present study was carried out to compare two commonly used strains of laboratory rats, Sprague-Dawley (SD) and Long-Evans (LE), between the ages of postnatal day (PND) 26-56 using high-throughput behavioral phenotyping tools commonly used in mouse models of ASD that we have adapted for use in rats. We detected few differences between young SD and LE strains on standard assays of exploration, sensorimotor gating, anxiety, repetitive behaviors, and learning. Both SD and LE strains also demonstrated sociability in the 3-chamber social approach test as indexed by spending more time in the social chamber with a constrained age/strain/sex matched novel partner than in an identical chamber without a partner. Pronounced differences between the two strains were, however, detected when the rats were allowed to freely interact with a novel partner in the social dyad paradigm. The SD rats in this particular testing paradigm engaged in play more frequently and for longer durations than the LE rats at both juvenile and young adult developmental time points. Results from this study that are particularly relevant for developing preclinical ASD models in rats are threefold: (i) commonly utilized strains exhibit unique patterns of social interactions, including strain-specific play behaviors, (ii) the testing environment may profoundly influence the expression of strain-specific social behavior and (iii) simple, automated measures of sociability may not capture the complexities of rat social interactions

PTF11kx: A Type Ia Supernova with Hydrogen Emission Persisting After 3.5 Years

The optical transient PTF11kx exhibited both the characteristic spectral features of Type Ia supernovae (SNe Ia) and the signature of ejecta interacting with circumstellar material (CSM) containing hydrogen, indicating the presence of a nondegenerate companion. We present an optical spectrum at $1342$ days after peak from Keck Observatory, in which the broad component of H$\alpha$ emission persists with a similar profile as in early-time observations. We also present $Spitzer$ IRAC detections obtained $1237$ and $1818$ days after peak, and an upper limit from $HST$ ultraviolet imaging at $2133$ days. We interpret our late-time observations in context with published results - and reinterpret the early-time observations - in order to constrain the CSM's physical parameters and compare to theoretical predictions for recurrent nova systems. We find that the CSM's radial extent may be several times the distance between the star and the CSM's inner edge, and that the CSM column density may be two orders of magnitude lower than previous estimates. We show that the H$\alpha$ luminosity decline is similar to other SNe with CSM interaction, and demonstrate how our infrared photometry is evidence for newly formed, collisionally heated dust. We create a model for PTF11kx's late-time CSM interaction and find that X-ray reprocessing by photoionization and recombination cannot reproduce the observed H$\alpha$ luminosity, suggesting that the X-rays are thermalized and that H$\alpha$ radiates from collisional excitation. Finally, we discuss the implications of our results regarding the progenitor scenario and the geometric properties of the CSM for the PTF11kx system.Comment: 15 pages, 8 figures, 3 tables; submitted to Ap

Neuropsychological Assessment of Cultrually and Linguistically Diverse Children: A Review of Relevant Issues and Appropraite Methods

Drawing from the fields of anatomy, biology, biophysics, ethology, pharmacology, physiology, physiological psychology, and philosophy, neuropsychology is the study of the relationship between human brain function and behavior (Kolb & Whishaw, 2003). According to Lezak (1995), the field of neuropsychology has grown to encompass the diagnosis of individuals, patient care and planning, rehabilitation and treatment evaluation, and research with regard to neuropsychological functioning. Assessment continues to be emphasized as a component of neuropsychology, and it typically involves an evaluation of the following domains: intellectual status, language and academic abilities, executive processes, attention, concentration, learning and memory, visuoconstructive abilities, motor functioning, sensory functioning, and emotional functioning, including mood, behavior, and personality (Groth-Marnat, 2000; Lezak, 1995; Spreen & Strauss, 1998)

A novel mechanism of RNase L inhibition: Theiler\u27s virus L* protein prevents 2-5A from binding to RNase L

<div><p>The OAS/RNase L pathway is one of the best-characterized effector pathways of the IFN antiviral response. It inhibits the replication of many viruses and ultimately promotes apoptosis of infected cells, contributing to the control of virus spread. However, viruses have evolved a range of escape strategies that act against different steps in the pathway. Here we unraveled a novel escape strategy involving Theiler’s murine encephalomyelitis virus (TMEV) L* protein. Previously we found that L* was the first viral protein binding directly RNase L. Our current data show that L* binds the ankyrin repeats R1 and R2 of RNase L and inhibits 2’-5’ oligoadenylates (2-5A) binding to RNase L. Thereby, L* prevents dimerization and oligomerization of RNase L in response to 2-5A. Using chimeric mouse hepatitis virus (MHV) expressing TMEV L*, we showed that L* efficiently inhibits RNase L <i>in vivo</i>. Interestingly, those data show that L* can functionally substitute for the MHV-encoded phosphodiesterase ns2, which acts upstream of L* in the OAS/RNase L pathway, by degrading 2-5A.</p></div

Constraining the Progenitor Companion of the Nearby Type Ia SN 2011fe with a Nebular Spectrum at +981 Days

We present an optical nebular spectrum of the nearby Type Ia supernova 2011fe, obtained 981 days after explosion. SN 2011fe exhibits little evolution since the +593 day optical spectrum, but there are several curious aspects in this new extremely late-time regime. We suggest that the persistence of the $\sim5800$~\AA\ feature is due to Na I D, and that a new emission feature at $\sim7300$~\AA\ may be [Ca II]. Also, we discuss whether the new emission feature at $\sim6400$~\AA\ might be [Fe I] or the high-velocity hydrogen predicted by Mazzali et al. The nebular feature at 5200~\AA\ exhibits a linear velocity evolution of $\sim350$ $\rm km\ s^{-1}$ per 100 days from at least +220 to +980 days, but the line's shape also changes in this time, suggesting that line blending contributes to the evolution. At $\sim 1000$ days after explosion, flux from the SN has declined to a point where contribution from a luminous secondary could be detected. In this work we make the first observational tests for a post-impact remnant star and constrain its temperature and luminosity to $T \gtrsim 10^4$ $\rm K$ and $L \lesssim 10^4$ $\rm L_{\odot}$. Additionally, we do not see any evidence for narrow H$\alpha$ emission in our spectrum. We conclude that observations continue to strongly exclude many single-degenerate scenarios for SN 2011fe.Comment: 11 pages, 10 figures, published by MNRA

SN 2015U: A Rapidly Evolving and Luminous Type Ibn Supernova

Supernova (SN) 2015U (also known as PSN J07285387+3349106) was discovered in NGC 2388 on 2015 Feb. 11. A rapidly evolving and luminous event, it showed effectively hydrogen-free spectra dominated by relatively narrow helium P-Cygni spectral features and it was classified as a SN Ibn. In this paper we present photometric, spectroscopic, and spectropolarimetric observations of SN 2015U, including a Keck/DEIMOS spectrum (resolution $\approx$ 5000) which fully resolves the optical emission and absorption features. We find that SN 2015U is best understood via models of shock breakout from extended and dense circumstellar material (CSM), likely created by a history of mass loss from the progenitor with an extreme outburst within $\sim$1-2 yr of core collapse (but we do not detect any outburst in our archival imaging of NGC 2388). We argue that the high luminosity of SN 2015U was powered not through $^{56}$Ni decay but via the deposition of kinetic energy into the ejecta/CSM shock interface. Though our analysis is hampered by strong host-galaxy dust obscuration (which likely exhibits multiple components), our dataset makes SN 2015U one of the best-studied Type Ibn supernovae and provides a bridge of understanding to other rapidly fading transients, both luminous and relatively faint.Comment: 20 pages, 15 figures, 4 table

Development of a Health Promotion Program: Targeting Adolescent Behaviors and Attitudes Toward Prescription Opioids

The current opioid epidemic kills an estimated four people every day in Massachusetts and is considered one of the greatest health threats to adolescents. Massachusetts state data indicates opioid addiction is a public health crisis, which requires the development of a health promotion program for adolescents and legislative action. The innovative eight-week middle school-based program Promote Opioid Prevention Program 4 Youth (POPPY) is implemented during Health and Wellness classes. POPPY is based on the Social Cognitive Theory, focusing on environmental and health behaviors. The goals of this distinct program are to: reduce adolescents\u27 misuse of prescription opioid medication, increase adolescents\u27 self-efficacy to make healthy decisions regarding misuse of prescription opioid medication, and to foster an environment conducive to preventing misuse of prescription opioid medication, while building social and self-management skills. The POPPY health promotion program will provide education that leads to development of health-related decision-making skills. Ultimately, healthier decisions lead to a reduction in opioid misuse risk factors such as peer pressure, social influence, curiosity, and experimentation. Protecting youth from health risks is critical to preventing fatalities associated with chronic conditions such as drug addiction that can lead to the onset of other major illnesses later-on in adulthood

Metabolic correlates of prevalent mild cognitive impairment and Alzheimer's disease in adults with Down syndrome.

IntroductionDisruption of metabolic function is a recognized feature of late onset Alzheimer's disease (LOAD). We sought to determine whether similar metabolic pathways are implicated in adults with Down syndrome (DS) who have increased risk for Alzheimer's disease (AD).MethodsWe examined peripheral blood from 292 participants with DS who completed baseline assessments in the Alzheimer's Biomarkers Consortium-Down Syndrome (ABC-DS) using untargeted mass spectrometry (MS). Our sample included 38 individuals who met consensus criteria for AD (DS-AD), 43 who met criteria for mild cognitive impairment (DS-MCI), and 211 who were cognitively unaffected and stable (CS).ResultsWe measured relative abundance of 8,805 features using MS and 180 putative metabolites were differentially expressed (DE) among the groups at false discovery rate-corrected q&lt; 0.05. From the DE features, a nine-feature classifier model classified the CS and DS-AD groups with receiver operating characteristic area under the curve (ROC AUC) of 0.86 and a two-feature model classified the DS-MCI and DS-AD groups with ROC AUC of 0.88. Metabolite set enrichment analysis across the three groups suggested alterations in fatty acid and carbohydrate metabolism.DiscussionOur results reveal metabolic alterations in DS-AD that are similar to those seen in LOAD. The pattern of results in this cross-sectional DS cohort suggests a dynamic time course of metabolic dysregulation which evolves with clinical progression from non-demented, to MCI, to AD. Metabolomic markers may be useful for staging progression of DS-AD

The Very Young Type Ia Supernova 2012cg: Discovery and Early-Time Follow-Up Observations

On 2012 May 17.2 UT, only 1.5 +/- 0.2 d after explosion, we discovered SN 2012cg, a Type Ia supernova (SN Ia) in NGC 4424 (d ~ 15 Mpc). As a result of the newly modified strategy employed by the Lick Observatory SN Search, a sequence of filtered images was obtained starting 161 s after discovery. Utilizing recent models describing the interaction of SN ejecta with a companion star, we rule out a ~1 M_Sun companion for half of all viewing angles and a red-giant companion for nearly all orientations. SN 2012cg reached a B-band maximum of 12.09 +/- 0.02 mag on 2012 June 2.0 and took ~17.3 d from explosion to reach this, typical for SNe Ia. Our pre-maximum brightness photometry shows a narrower-than-average B-band light curve for SN 2012cg, though slightly overluminous at maximum brightness and with normal color evolution (including some of the earliest SN Ia filtered photometry ever obtained). Spectral fits to SN 2012cg reveal ions typically found in SNe Ia at early times, with expansion velocities >14,000 km/s at 2.5 d past explosion. Absorption from C II is detected early, as well as high-velocity components of both Si II 6355 Ang. and Ca II. Our last spectrum (13.5 d past explosion) resembles that of the somewhat peculiar SN Ia 1999aa. This suggests that SN 2012cg will have a slower-than-average declining light curve, which may be surprising given the faster-than-average rising light curve.Comment: re-submitted to ApJL, 4 figures, 1 tabl