Cue-induced reinstatement of alcohol-seeking behavior is associated with increased CaMKII T286 phosphorylation in the reward pathway of mice

Cue-induced reinstatement of alcohol-seeking is a hallmark behavioral pathology of addiction. Evidence suggests that reinstatement (e.g., relapse), may be regulated by cell signaling systems that underlie neuroplasticity. A variety of plasticity events require activation of calcium calmodulin-dependent protein kinase II (CaMKII) in components of the reward pathway, such as the nucleus accumbens and amygdala. We sought to determine if cue-induced reinstatement of alcohol-seeking behavior is associated with changes in the activation state (e.g., phosphorylation) of CaMKII-T286. Male C57BL/6J mice (n = 14) were trained to lever press on a fixed-ratio-4 schedule of sweetened alcohol (2% sucrose + 9% EtOH) reinforcement. After 14-d of extinction (no cues or reinforcers), mice underwent a response-contingent reinstatement (n = 7) vs. an additional day of extinction (n = 7). Brains were removed immediately after the test and processed for evaluation of pCaMKII-T286 immunoreactivity (IR). Number of pCaMKII-T286 positive cells/mm2 was quantified from coronal brain sections using Bioquant Image Analysis software. Mice emitted significantly more responses on the alcohol vs. the inactive lever throughout the baseline phase with average alcohol intake of 1.1 ± 0.03 g/kg/1-h. During extinction, responses on the alcohol lever decreased to inactive lever levels by day 7. Significant cue-induced reinstatement of alcohol-seeking was observed during a single test with no effects on the inactive lever. Reinstatement was associated with increased pCaMKII-T286 IR specifically in amygdala (LA and BLA), nucleus accumbens (AcbSh), lateral septum, mediodorsal thalamus, and piriform cortex as compared to extinction control. Brain regions showing no change included the dorsal striatum, medial septum, cingulate cortex, habenula, paraventricular thalamus, and ventral hypothalamus. These results show response contingent cue-induced reinstatement of alcohol-seeking behavior is associated with selective increases in pCaMKII-T286 in specific reward- and memory-related brain regions of male C57BL/6J mice. Primary molecular mechanisms of associative learning and memory may regulate relapse in alcohol addiction

Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE) Conceptual Design Report Volume 2: The Physics Program for DUNE at LBNF

The Physics Program for the Deep Underground Neutrino Experiment (DUNE) at the Fermilab Long-Baseline Neutrino Facility (LBNF) is described

Urban biodiversity : State of the science and future directions

Since the 1990s, recognition of urban biodiversity research has increased steadily. Knowledge of how ecological communities respond to urban pressures can assist in addressing global questions related to biodiversity. To assess the state of this research field in meeting this aim, we conducted a systematic review of the urban biodiversity literature published since 1990. We obtained data from 1209 studies that sampled ecological communities representing 12 taxonomic groups. While advances have been made in the field over the last 30 years, we found that urban biodiversity research has primarily been conducted in single cities within the Palearctic and Nearctic realms, within forest remnants and residential locations, and predominantly surveys plants and birds, with significant gaps in research within the Global South and little integration of multi-species and multi-trophic interactions. Sample sizes remain limited in spatial and temporal scope, but citizen science and remote sensing resources have broadened these efforts. Analytical approaches still rely on taxonomic diversity to describe urban plant and animal communities, with increasing numbers of integrated phylogenetic and trait-based analyses. Despite the implementation of nature-based solutions across the world's cities, only 5% of studies link biodiversity to ecosystem function and services, pointing to substantial gaps in our understanding of such solutions. We advocate for future research that encompasses a greater diversity of taxonomic groups and urban systems, focusing on biodiversity hotspots. Implementing such research would enable researchers to move forward in an equitable and multidisciplinary way to tackle the complex issues facing global urban biodiversity.Peer reviewe

Measurement of νˉμ\bar{\nu}_{\mu} and νμ\nu_{\mu} charged current inclusive cross sections and their ratio with the T2K off-axis near detector

We report a measurement of cross section $\sigma(\nu_{\mu}+{\rm nucleus}\rightarrow\mu^{-}+X)$ and the first measurements of the cross section $\sigma(\bar{\nu}_{\mu}+{\rm nucleus}\rightarrow\mu^{+}+X)$ and their ratio $R(\frac{\sigma(\bar \nu)}{\sigma(\nu)})$ at (anti-)neutrino energies below 1.5 GeV. We determine the single momentum bin cross section measurements, averaged over the T2K $\bar{\nu}/\nu$-flux, for the detector target material (mainly Carbon, Oxygen, Hydrogen and Copper) with phase space restricted laboratory frame kinematics of $\theta_{\mu}$500 MeV/c. The results are $\sigma(\bar{\nu})=\left( 0.900\pm0.029{\rm (stat.)}\pm0.088{\rm (syst.)}\right)\times10^{-39}$ and $\sigma(\nu)=\left( 2.41\ \pm0.022{\rm{(stat.)}}\pm0.231{\rm (syst.)}\ \right)\times10^{-39}$in units of cm$^{2}$/nucleon and$R\left(\frac{\sigma(\bar{\nu})}{\sigma(\nu)}\right)= 0.373\pm0.012{\rm (stat.)}\pm0.015{\rm (syst.)}$.Comment: 18 pages, 8 figure

A Meta-Analysis of the Existing Knowledge of Immunoreactivity against Hepatitis C Virus (HCV)

Approximately 3% of the world population is infected by HCV, which represents a major global health challenge. Almost 400 different scientific reports present immunological data related to T cell and antibody epitopes derived from HCV literature. Analysis of all HCV-related epitope hosted in the Immune Epitope Database (IEDB), a repository of freely accessible immune epitope data, revealed more than 1500 and 1900 distinct T cell and antibody epitopes, respectively. The inventory of all data revealed specific trends in terms of the host and the HCV genotypes from which sequences were derived. Upon further analysis we found that this large number of epitopes reflects overlapping structures, and homologous sequences derived from different HCV isolates. To access and visualize this information we developed a novel strategy that assembles large sets of epitope data, maps them onto reference genomes and displays the frequency of positive responses. Compilation of the HCV immune reactivity from hundreds of different studies, revealed a complex and thorough picture of HCV immune epitope data to date. The results pinpoint areas of more intense reactivity or research activities at the level of antibody, CD4 and CD8 responses for each of the individual HCV proteins. In general, the areas targeted by the different effector immune functions were distinct and antibody reactivity was positively correlated with hydrophilicity, while T cell reactivity correlated with hydrophobicity. At the sequence level, epitopes frequently recognized by both T cell and B cell correlated with low variability, and our analysis thus highlighted areas of potential interest for practical applications. The human reactivity was further analyzed to pinpoint differential patterns of reactivity associated with acute versus chronic infection, to reveal the apparent impact of glycosylation on T cell, but not antibody responses, and to highlight a paucity of studies involved antibody epitopes associated with virus neutralization

Seasonal Variation of Multiple-Muon Cosmic Ray Air Showers Observed in the NOvA Detector on the Surface

We report the rate of cosmic ray air showers with multiplicities exceeding 15 muon tracks recorded in the NOvA Far Detector between May 2016 and May 2018. The detector is located on the surface under an overburden of 3.6 meters water equivalent. We observe a seasonal dependence in the rate of multiple-muon showers, which varies in magnitude with multiplicity and zenith angle. During this period, the effective atmospheric temperature and surface pressure ranged between 210 K to 230 K and 940mbar to 990mbar, respectively; the shower rates are anti-correlated with the variation in the effective temperature. The variations are about 30% larger for the highest multiplicities than the lowest multiplicities and 20% larger for showers near the horizon than vertical showers

Measurement of the νe−\nu_e-Nucleus Charged-Current Double-Differential Cross Section at <Eν>=\left< E_{\nu} \right> = 2.4 GeV using NOvA

The inclusive electron neutrino charged-current cross section is measured in the NOvA near detector using $8.02\times10^{20}$ protons-on-target (POT) in the NuMI beam. The sample of GeV electron neutrino interactions is the largest analyzed to date and is limited by $\simeq$ 17\% systematic rather than the $\simeq$ 7.4\% statistical uncertainties. The double-differential cross section in final-state electron energy and angle is presented for the first time, together with the single-differential dependence on $Q^{2}$ (squared four-momentum transfer) and energy, in the range 1 GeV $\leq E_{\nu} <$6 GeV. Detailed comparisons are made to the predictions of the GENIE, GiBUU, NEUT, and NuWro neutrino event generators. The data do not strongly favor a model over the others consistently across all three cross sections measured, though some models have especially good or poor agreement in the single differential cross section vs. $Q^{2}$

An Improved Measurement of Neutrino Oscillation Parameters by the NOvA Experiment

We present new $\nu_\mu\rightarrow\nu_e$, $\nu_\mu\rightarrow\nu_\mu$, $\overline{\nu}_\mu\rightarrow\overline{\nu}_e$, and $\overline{\nu}_\mu\rightarrow\overline{\nu}_\mu$ oscillation measurements by the NOvA experiment, with a 50% increase in neutrino-mode beam exposure over the previously reported results. The additional data, combined with previously published neutrino and antineutrino data, are all analyzed using improved techniques and simulations. A joint fit to the $\nu_e$, $\nu_\mu$, $\overline{\nu}_e$, and $\overline{\nu}_\mu$ candidate samples within the 3-flavor neutrino oscillation framework continues to yield a best-fit point in the normal mass ordering and the upper octant of the $\theta_{23}$ mixing angle, with $\Delta m^{2}_{32} = (2.41\pm0.07)\times 10^{-3}$ eV$^2$ and $\sin^2\theta_{23} = 0.57^{+0.03}_{-0.04}$. The data disfavor combinations of oscillation parameters that give rise to a large asymmetry in the rates of $\nu_e$ and $\overline{\nu}_e$ appearance. This includes values of the CP-violating phase in the vicinity of $\delta_\text{CP} = \pi/2$ which are excluded by $>3\sigma$ for the inverted mass ordering, and values around $\delta_\text{CP} = 3\pi/2$ in the normal ordering which are disfavored at 2$\sigma$ confidence.Comment: 11 pages, 6 figures. Supplementary material attached (7 figures

Measurement of the Double-Differential Muon-neutrino Charged-Current Inclusive Cross Section in the NOvA Near Detector

We report cross-section measurements of the final-state muon kinematics for \numu charged-current interactions in the NOvA near detector using an accumulated 8.09$\times10^{20}$ protons-on-target (POT) in the NuMI beam. We present the results as a double-differential cross section in the observed outgoing muon energy and angle, as well as single-differential cross sections in the derived neutrino energy, $E_\nu$, and square of the four-momentum transfer, $Q^2$. We compare the results to inclusive cross-section predictions from various neutrino event generators via $\chi^2$ calculations using a covariance matrix that accounts for bin-to-bin correlations of systematic uncertainties. These comparisons show a clear discrepancy between the data and each of the tested predictions at forward muon angle and low $Q^2$, indicating a missing suppression of the cross section in current neutrino-nucleus scattering models