First Simultaneous Measurement of Differential Muon-Neutrino Charged-Current Cross Sections on Argon for Final States with and without Protons Using MicroBooNE Data.

We report the first double-differential neutrino-argon cross section measurement made simultaneously for final states with and without protons for the inclusive muon neutrino charged-current interaction channel. The proton kinematics of this channel are further explored with a differential cross section measurement as a function of the leading proton's kinetic energy that extends across the detection threshold. These measurements use data collected with the MicroBooNE detector from 6.4×10^{20} protons on target from the Fermilab booster neutrino beam with a mean neutrino energy of ∼0.8 GeV. Extensive data-driven model validation utilizing the conditional constraint formalism is employed. This motivates enlarging the uncertainties with an empirical reweighting approach to minimize the possibility of extracting biased cross section results. The extracted nominal flux-averaged cross sections are compared to widely used event generator predictions revealing severe mismodeling of final states without protons for muon neutrino charged-current interactions, possibly from insufficient treatment of final state interactions. These measurements provide a wealth of new information useful for improving event generators which will enhance the sensitivity of precision measurements in neutrino experiments.

First Search for Dark-Trident Processes Using the MicroBooNE Detector.

We present a first search for dark-trident scattering in a neutrino beam using a dataset corresponding to 7.2×10^{20} protons on target taken with the MicroBooNE detector at Fermilab. Proton interactions in the neutrino target at the main injector produce π^{0} and η mesons, which could decay into dark-matter (DM) particles mediated via a dark photon A^{'}. A convolutional neural network is trained to identify interactions of the DM particles in the liquid-argon time projection chamber (LArTPC) exploiting its imagelike reconstruction capability. In the absence of a DM signal, we provide limits at the 90% confidence level on the squared kinematic mixing parameter ϵ^{2} as a function of the dark-photon mass in the range 10≤M_{A^{'}}≤400 MeV. The limits cover previously unconstrained parameter space for the production of fermion or scalar DM particles χ for two benchmark models with mass ratios M_{χ}/M_{A^{'}}=0.6 and 2 and for dark fine-structure constants 0.1≤α_{D}≤1.

Search for Heavy Neutral Leptons in Electron-Positron and Neutral-Pion Final States with the MicroBooNE Detector.

We present the first search for heavy neutral leptons (HNLs) decaying into νe^{+}e^{-} or νπ^{0} final states in a liquid-argon time projection chamber using data collected with the MicroBooNE detector. The data were recorded synchronously with the NuMI neutrino beam from Fermilab's main injector corresponding to a total exposure of 7.01×10^{20} protons on target. We set upper limits at the 90% confidence level on the mixing parameter |U_{µ4}|^{2} in the mass ranges 10≤m_{HNL}≤150 MeV for the νe^{+}e^{-} channel and 150≤m_{HNL}≤245 MeV for the νπ^{0} channel, assuming |U_{e4}|^{2}=|U_{τ4}|^{2}=0. These limits represent the most stringent constraints in the mass range 35

A comparison of the kinematics and kinetics of barefoot and shod running in children with cerebral palsy.

BACKGROUND: The biomechanics of barefoot and shod running are different for typically developing children but unknown for children with cerebral palsy (CP). Such differences may have implications for injury and performance. AIMS: The primary aims of this study were to compare the lower limb biomechanics of barefoot and shod running in children with CP, and to determine whether any differences were the same in GMFCS levels I and II. METHODS: This cross-sectional study examined 38 children with CP (n = 24 (GMFCS) level I; n = 14 GMFCS II), running overground at 3 speeds (jog, run, sprint) in barefoot and shod conditions. Marker trajectories and force plate data were recorded, and lower limb kinematics, kinetics and spatiotemporal variables were derived. Differences between barefoot and shod running were analysed using linear mixed models. RESULTS: For both GMFCS levels, barefoot running resulted in higher loading rates, but smaller impact peaks at all speeds. Barefoot running was associated with greater hip and knee power; less ankle dorsiflexion and hip flexion at initial contact, and less ankle and knee range of motion during stance, compared to shod running, at all speeds. Barefoot stride length was shortened, and cadence increased compared to shod during jogging and running but not sprinting. For GMFCS level I only, barefoot running involved a higher incidence of forefoot strike, greater ankle power generation and less hip range of motion during stance. SIGNIFICANCE: Running barefoot may facilitate running performance by increasing power generation at the ankle in children with CP, GMFCS level I. Higher barefoot loading rates may have implications for performance and injury.

The effect of a low-load plyometric running intervention on leg stiffness in youth with cerebral palsy: A randomised controlled trial.

AIM: To determine whether a running intervention utilising plyometric activities improved leg stiffness in youth with cerebral palsy (CP), GMFCS levels I and II. METHOD: This stratified randomised controlled trial examined the lower limb kinetics and kinematics of a sample of youths with CP during sub-maximal hopping and running, prior to and immediately following a 12-week running intervention that incorporated low load plyometric training. Included participants were 13 in the control group (mean age 13 years 2 months [SD 2 years 7 months]; six males; nine GMFCS level I; six unilateral) and 18 in the intervention group (mean age 12 years 9 months [SD 2 years 10 months]; 13 males; 11 GMFCS level I; nine unilateral). Derived variables included three-dimensional leg stiffness as well as resultant ground reaction force and change in leg length. Generalised linear mixed models were developed for statistical analysis. RESULTS: At follow-up the intervention group had greater leg stiffness than the control group during submaximal hopping (Intervention median = 3278Nm-1; Control median = 1556Nm-1; p < 0.01). At follow-up, participants in the intervention group in GMFCS Level I had greater leg stiffness than the control group during jogging (Intervention mean=38.84 (SD=25.55); Control mean=29.38 (SD=11.11); t = 2.61 p = 0.01). INTERPRETATION: A running training intervention which includes plyometric activities can improve leg stiffness in young people with CP, especially those in GMFCS level I.

A comparison of leg stiffness in running between typically developing children and children with cerebral palsy.

BACKGROUND: Leg stiffness is important during running to increase velocity and maximise efficiency by facilitating use of the stretch-shortening cycle. Children with cerebral palsy who have neuromuscular impairments may have altered leg stiffness. The aim of this study was to describe leg stiffness during running in typically developing children and those with cerebral palsy in Gross Motor Function Classification Scale levels I and II at a range of speeds. METHODS: This cross-sectional study examined kinematic data collected from typically developing children (n = 21) and children with cerebral palsy (Gross Motor Function Classification Scale level I n = 25, Gross Motor Function Classification Scale level II n = 13) during jogging, running and sprinting. Derived variables were resultant ground reaction force, change in leg length and three-dimensional leg stiffness. Linear mixed models were developed for statistical analysis. FINDINGS: Children with cerebral palsy had reduced stiffness when jogging (Gross Motor Function Classification Scale level I affected t = 3.81 p < 0.01; non-affected t = 2.19 p = 0.03; Gross Motor Function Classification Scale level II affected t = 2.04 p = 0.04) and running (Gross Motor Function Classification Scale level I affected t = 3.23 p < 0.01) compared to typically developing children. Affected legs were less stiff than non-affected legs only in Gross Motor Function Classification Scale level I during running (t = 2.26 p = 0.03) and sprinting (t = 2.95 p < 0.01). INTERPRETATION: Children with cerebral palsy have atypical leg stiffness profiles which differ according to functional classification.

Search for Electron Antineutrino Appearance in a Long-Baseline Muon Antineutrino Beam.

Electron antineutrino appearance is measured by the T2K experiment in an accelerator-produced antineutrino beam, using additional neutrino beam operation to constrain parameters of the Pontecorvo-Maki-Nakagawa-Sakata (PMNS) mixing matrix. T2K observes 15 candidate electron antineutrino events with a background expectation of 9.3 events. Including information from the kinematic distribution of observed events, the hypothesis of no electron antineutrino appearance is disfavored with a significance of 2.40σ and no discrepancy between data and PMNS predictions is found. A complementary analysis that introduces an additional free parameter which allows non-PMNS values of electron neutrino and antineutrino appearance also finds no discrepancy between data and PMNS predictions.

The effect of a running training intervention on ankle power generation in children and adolescents with cerebral palsy: A randomized controlled trial.

BACKGROUND: Children and adolescents with cerebral palsy who are classified as Gross Motor Function Classification Scale level I or II are usually able to run but lack ankle power generation for push-off. The aim of this study was to analyze the efficacy of a running training program in improving ankle power generation in children and adolescents with cerebral palsy. METHODS: This randomized controlled trial compared kinematic and spatiotemporal data collected during running from 38 children and adolescents with unilateral or bilateral cerebral palsy before and after a 12-week running program. Normalized speed, stride length, cadence, foot strike pattern, peak ankle power generation, peak hip flexor power generation in swing and propulsion strategy were calculated. Linear mixed models were developed to analyze differences between groups. FINDINGS: At follow-up the intervention group had increased normalized speed of running (t = -3.68 p < .01) while the control group got slower (t = 3.17 p < .01). In running, children in Gross Motor Function Classification Scale level II in the intervention group increased ankle power (t = 2.49 p = .01) while the control group did not change (t = 0.38 p = .71). In sprinting, children in Gross Motor Function Classification Scale levels I and II in the intervention group maintained ankle power (level I t = 0.32 p = .75; level II t = 1.56 p = .12) while those in the control group decreased ankle power (level I t = 4.69 p < .01; level II t = 2.52 p = .01). Most within-group differences did not result in significant between-group differences at follow-up. INTERPRETATION: Power generation for running may be responsive to targeted intervention in children with cerebral palsy.

Telephone outreach by community workers to improve uptake of NHS Health Checks in more deprived localities and minority ethnic groups: a qualitative investigation of implementation.

BACKGROUND: NHS Health Checks is a national cardiovascular risk assessment and management programme in England. To improve equity of uptake in more deprived, and Black, Asian and minority ethnic (BAME) communities, a novel telephone outreach intervention was developed. The outreach call included an invitation to an NHS Health Check appointment, lifestyle questions, and signposting to lifestyle services. We examined the experiences of staff delivering the intervention. METHODS: Thematic analysis of semi-structured interviews with 10 community Telephone Outreach Workers (TOWs) making outreach calls, and 5 Primary Care Practice (PCP) staff they liaised with. Normalization Process Theory was used to examine intervention implementation. RESULTS: Telephone outreach was perceived as effective in engaging patients in NHS Health Checks and could reduce related administration burdens on PCPs. Successful implementation was dependent on support from participating PCPs, and tensions between the intervention and other PCP priorities were identified. Some PCP staff lacked clarity regarding the intervention aim and this could reduce the potential to capitalize on TOWs' specialist skills. CONCLUSIONS: To maximize the potential of telephone outreach to impact equity, purposeful recruitment and training of TOWs is vital, along with support and integration of TOWs, and the telephone outreach intervention, in participating PCPs.

Nutritional strategies of British professional and amateur natural bodybuilders during competition preparation.

BACKGROUND: To prepare for competition, bodybuilders employ strategies based around: energy restriction, resistance training, cardiovascular exercise, isometric "posing", and supplementation. Cohorts of professional (PRO) natural bodybuilders offer insights into how these strategies are implemented by elite competitors, and are undocumented in the scientific literature. METHODS: Forty-seven competitors (33 male (8 PRO, 25 amateur (AMA), 14 female (5 PRO, 9 AMA) participated in the study. All PROs were eligible to compete with the Drug Free Athletes Coalition (DFAC), and all AMAs were recruited from the British Natural Bodybuilding Federation (BNBF). Competitors in these organisations are subject to a polygraph and are drug tested in accordance with the World Anti-Doping Agency. We report the results of a cross-sectional study of drug free bodybuilders competing at BNBF qualifying events, and the DFAC and World Natural Bodybuilding Federation finals. Participants completed a 34-item questionnaire assessing dietary intake at three time points (start, middle and end) of competition preparation. Participants recorded their food intake over a 24-h period in grams and/or portions. Dietary intakes of PRO and AMA competitors were then compared. Repeated measures ANOVA was used to test if nutrient intake changed over time, and for associations with division. RESULTS: Male PROs reported significantly (p < 0.05) more bodybuilding experience than AMAs (PRO: 12.3 +/- 9.2, AMA: 2.4 +/- 1.4 yrs). Male PROs lost less body mass per week (PRO: 0.5 +/- 0.1, AMA: 0.7 +/- 0.2%, p < 0.05), and reported more weeks dieting (PRO: 28.1 +/- 8.1, AMA: 21.0 +/- 9.4 wks, P = 0.06). Significant differences (p < 0.05) of carbohydrate and energy were also recorded, as well as a difference (p = 0.03) in the estimated energy deficit (EED), between male PRO (2.0 +/- 5.5 kcal) and AMA (- 3.4 +/- 5.5 kcal) competitors. CONCLUSIONS: Longer diets and slower weight loss utilized by PROs likely contributed towards a lower EED compared to the AMAs. Slower weight loss may constitute an effective strategy for maintaining energy availability and muscle mass during an energy deficit. These findings require corroboration, but will interest bodybuilders and coaches.

Using genotyping-by-sequencing to predict gender in animals.

Gender assignment errors are common in some animal species and lead to inaccuracies in downstream analyses. Procedures for detecting gender misassignment are available for array-based SNP data but are still being developed for genotyping-by-sequencing (GBS) data. In this study, we describe a method for using GBS data to predict gender using X and Y chromosomal SNPs. From a set of 1286 X chromosomal and 23 Y chromosomal deer (Cervus sp.) SNPs discovered from GBS sequence reads, a prediction model was built using a training dataset of 422 Red deer and validated using a test dataset of 868 Red deer and Wapiti deer. Prediction was based on the proportion of heterozygous genotypes on the X chromosome and the proportion of non-missing genotypes on the Y chromosome observed in each individual. The concordance between recorded gender and predicted gender was 98.6% in the training dataset and 99.3% in the test dataset. The model identified five individuals across both datasets with incorrect recorded gender and was unable to predict gender for another five individuals. Overall, our method predicted gender with a high degree of accuracy and could be used for quality control in gender assignment datasets or for assigning gender when unrecorded, provided a suitable reference genome is available.

The effect of joint translation constraint on within-participant variability of kinematics and kinetics during running in cerebral palsy.

BACKGROUND: Biomechanical data in cerebral palsy are inherently variable but no optimal model of translational joint constraint has been identified. The primary aim of this study was to determine which model of translational joint constraint resulted in the lowest within-participant variability of lower limb joint angles and moments. The secondary aim was to determine which model best distinguished known functional groups in Cerebral Palsy. METHODS: Three models (three degrees of freedom, six degrees of freedom and six degrees of freedom with specified joint translation constraint) were applied to data from running trials of 40 children with cerebral palsy. FINDINGS: Joint angle standard deviations were largest using the six degrees of freedom model and smallest using the constrained six degrees of freedom model (p < 0.050). For all joints in all planes of motion, joint moment standard deviations were largest using the six degrees of freedom model and smallest using the constrained six degrees of freedom model; standard deviations using the constrained model were smaller than the three degrees of freedom model by 10-30% of moment magnitude (0.01-0.03 Nm/kg; p < 0.001). The six degrees of freedom models distinguished functional subgroups with larger effect size than the three degrees of freedom model only for hip power generation in swing. INTERPRETATION: A model with specified joint constraint minimized within-participant variability during running and was useful for detecting differences in functional capacity in cerebral palsy.

Propulsion strategy in running in children and adolescents with cerebral palsy.

BACKGROUND: Running is a fundamental movement skill important for participation in physical activity. Children with cerebral palsy (CP) who are classified at Gross Motor Function Classification Scale (GMFCS) level I and II are able to run but may be limited by neuromuscular impairments. RESEARCH QUESTION: To describe the propulsion strategy (PS) during running of children and adolescents with CP. METHODS: This cross-sectional study used kinematic and kinetic data collected during running from 40 children and adolescents with unilateral or bilateral CP and 21 typically developing (TD) children. Maximum speed, peak ankle power generation (A2), peak hip flexor power generation in swing (H3) and PS (PS = A2/(A2 + H3)) were calculated. Linear mixed models were developed to analyze differences between groups. RESULTS: Maximum speed, A2 and PS were significantly less in children with CP GMFCS level I than in TD children and significantly less in children in GMFCS level II than level I. For children with CP, A2 and PS were significantly smaller in affected legs than non-affected legs. In affected legs, H3 was significantly larger in children in GMFCS level II than GMFCS level I but not different between TD children and children in GFMCS level II. SIGNIFICANCE: The contribution of ankle plantarflexor power to forward propulsion in running is reduced in young people with CP and is related to GMFCS level. This deficit appears to be compensated in part by increased hip flexor power generation but limits maximum sprinting speed.

Search for CP Violation in Neutrino and Antineutrino Oscillations by the T2K Experiment with 2.2×10

The T2K experiment measures muon neutrino disappearance and electron neutrino appearance in accelerator-produced neutrino and antineutrino beams. With an exposure of 14.7(7.6)×10^{20} protons on target in the neutrino (antineutrino) mode, 89 ν_{e} candidates and seven anti-ν_{e} candidates are observed, while 67.5 and 9.0 are expected for δ_{CP}=0 and normal mass ordering. The obtained 2σ confidence interval for the CP-violating phase, δ_{CP}, does not include the CP-conserving cases (δ_{CP}=0, π). The best-fit values of other parameters are sin^{2}θ_{23}=0.526_{-0.036}^{+0.032} and Δm_{32}^{2}=2.463_{-0.070}^{+0.071}×10^{-3} eV^{2}/c^{4}.

Nutritional strategies of high level natural bodybuilders during competition preparation.

BACKGROUND: Competitive bodybuilders employ a combination of resistance training, cardiovascular exercise, calorie reduction, supplementation regimes and peaking strategies in order to lose fat mass and maintain fat free mass. Although recommendations exist for contest preparation, applied research is limited and data on the contest preparation regimes of bodybuilders are restricted to case studies or small cohorts. Moreover, the influence of different nutritional strategies on competitive outcome is unknown. METHODS: Fifty-one competitors (35 male and 16 female) volunteered to take part in this project. The British Natural Bodybuilding Federation (BNBF) runs an annual national competition for high level bodybuilders; competitors must qualify by winning at a qualifying events or may be invited at the judge's discretion. Competitors are subject to stringent drug testing and have to undergo a polygraph test. Study of this cohort provides an opportunity to examine the dietary practices of high level natural bodybuilders. We report the results of a cross-sectional study of bodybuilders competing at the BNBF finals. Volunteers completed a 34-item questionnaire assessing diet at three time points. At each time point participants recorded food intake over a 24-h period in grams and/or portions. Competitors were categorised according to contest placing. A "placed" competitor finished in the top 5, and a "Non-placed" (DNP) competitor finished outside the top 5. Nutrient analysis was performed using Nutritics software. Repeated measures ANOVA and effect sizes (Cohen's d) were used to test if nutrient intake changed over time and if placing was associated with intake. RESULTS: Mean preparation time for a competitor was 22 ± 9 weeks. Nutrient intake of bodybuilders reflected a high-protein, high-carbohydrate, low-fat diet. Total carbohydrate, protein and fat intakes decreased over time in both male and female cohorts (P < 0.05). Placed male competitors had a greater carbohydrate intake at the start of contest preparation (5.1 vs 3.7 g/kg BW) than DNP competitors (d = 1.02, 95% CI [0.22, 1.80]). CONCLUSIONS: Greater carbohydrate intake in the placed competitors could theoretically have contributed towards greater maintenance of muscle mass during competition preparation compared to DNP competitors. These findings require corroboration, but will likely be of interest to bodybuilders and coaches.

Down-regulation of the liver-derived plasma protein fetuin-B mediates reversible female infertility.

STUDY QUESTION: Does antisense oligonucleotide (ASO)-mediated down-regulation of serum fetuin-B cause infertility like fetuin-B gene deficiency in female mice? SUMMARY ANSWER: Pharmacological fetuin-B down-regulation by ASO therapy results in reversible infertility in female mice. WHAT IS KNOWN ALREADY: Female fetuin-B deficient (Fetub-/-) mice are infertile owing to premature zona pellucida (ZP) hardening. Enzyme activity studies demonstrated that fetuin-B is a potent and highly specific inhibitor of the zona proteinase ovastacin, which cleaves ZP protein 2 (ZP2) and thus mediates definitive ZP hardening. STUDY DESIGN, SIZE, DURATION: Ten fetuin-B ASO boli (100 mg/kg) were injected s.c. over 20 days in 12 female mice, and 10 phosphate-buffered saline (PBS)-treated mice were used as control. At day 20 females were mated to evaluate fetuin-B as a potential molecular target for contraception. ASO and PBS treatment was continued for ten injections. After treatment cessation at day 50, mating was continued to investigate if infertility was reversible. PARTICIPANTS/MATERIALS, SETTING, METHODS: We generated fetuin-B/ovastacin double deficient (Fetub-/-, Astl-/-) mice by conventional breeding to test if fertility of Fetub-/- female mice was restored when the target proteinase would likewise be deleted. At least five matings with each female genotype (Fetub-/- single deficient, Astl-/- single deficient, Fetub-/-, Astl-/- double deficient) were performed. To test the contraceptive effect of fetuin-B down-regulation, 22 female mice (6-13 weeks old) were treated with repetitive boli of 100 mg/kg fetuin-B ASO (n = 12) or PBS (n = 10) and mated continuously. Serum fetuin-B was determined by immunoblot before, during and after the ASO treatment. After 3 weeks of ASO treatment, in 6 females Fetub mRNA in liver was analyzed by PCR, and six PBS-treated females were used as control. Aspartate (AST) and alanine aminotransferase (ALT) were also measured in serum of six mice in each group. To determine the minimum permissive serum fetuin-B concentration required for successful fertilization IVF was performed in five fetuin-B ASO-treated mice. As a control, six females were injected with control oligonucleotides and six females were left untreated. MAIN RESULTS AND THE ROLE OF CHANCE: Fertility of Fetub-/- female mice was restored by additional ovastacin deficiency (Astl-/-). Unlike Fetub-/- mice, female Fetub-/-, Astl-/- mice were fertile, confirming ovastacin as a primary molecular target of fetuin-B. At day 20, after receiving 10 fetuin-B ASO boli, serum fetuin-B was down-regulated to 8 ± 6% (mean ± SD) of baseline level. Fetuin-B down-regulation was confirmed at the mRNA level. Fetuin-B ASO-treated females had 12.1 ± 3.1% of the liver Fetub mRNA level seen in PBS-treated females. In the following mating study, 11 out of 12 mated females failed to become pregnant during 50 days of ASO treatment and continuous mating from day 20 onwards. IVF of oocytes derived from ASO-treated females suggested that a serum fetuin-B level of less than 10 µg/ml was required to prevent pregnancy. Withdrawal of ASO treatment normalized serum fetuin-B and restored fertility; all female mice became pregnant and had litters within 60.3 ± 35.9 days after cessation of ASO treatment. The first litter was significantly smaller than that of control mice (4.6 ± 2.3 versus 6.7 ± 1.8 pups, n = 20, P = 0.04) but the smaller litter size was only temporary. The size of the second litter was similar to the first litter of control mice (7.6 ± 1.3 versus 6.7 ± 1.8 pups, n = 18, P = 0.25). LIMITATIONS, REASONS FOR CAUTION: The repeated dose of 100 mg/kg fetuin-B ASO boli caused an increased serum ALT and AST activity, suggesting hepatotoxicity. Daily vaginal plug checks indicated successful mating, but mating plugs in ASO-treated mice were less stable (vaginal tract not closed) than in control mice. WIDER IMPLICATIONS OF THE FINDINGS: Pharmacological fetuin-B down-regulation in mice caused reversible infertility. Control of ovastacin proteinase activity by fetuin-B is a necessary determinant of female fertility that can serve as a target for female contraception. Although promising in terms of human contraception, further studies analyzing the balance between sufficient fetuin-B down-regulation and tolerable side effects are required to improve safety before transfer into human reproductive biology can be considered. LARGE SCALE DATA: None. STUDY FUNDING AND COMPETING INTERESTS: The research was supported by a grant from Deutsche Forschungsgemeinschaft and by the START program of the Medical Faculty of RWTH Aachen University. The authors E.D., J.F. and W.J.-D. are named inventors on a patent application of RWTH Aachen University covering the use of fetuin-B in ovary and oocyte culture. No conflict of interest is declared by C.S. and A.C.

Distributions of oxytocin and vasopressin 1a receptors in the Taiwan vole and their role in social monogamy.

Social monogamy is a mating strategy rarely employed by mammalian species. Laboratory studies in socially monogamous prairie voles (Microtus ochrogaster) demonstrate that oxytocin and vasopressin act within the mesolimbic dopamine pathway to facilitate pair-bond formation. Species differences in oxytocin receptor (OTR) and vasopressin 1a receptor (V1aR) distribution in this pathway are associated with species differences in mating strategy. Here we characterize the neuroanatomical distribution of OTR and V1aR binding sites in naturally occurring populations of Taiwan voles (M. kikuchii), which purportedly display social monogamy. Live trapping was conducted at two sites in 2009-2010 and receptor autoradiography for OTR and V1aR was performed on brains from 24 animals. OTR binding in two brain regions where OTR signaling regulates pair-bonding were directly compared with that of prairie voles. Our results show that like prairie voles, Taiwan voles exhibit OTR in the prefrontal cortex, insular cortex, claustrum, nucleus accumbens, caudate-putamen, dorsal lateral septal nucleus, central amygdala, and ventromedial hypothalamus. Unlike prairie voles, Taiwan voles exhibit OTR binding in the CA3 pathway of the hippocampus, as well as the indusium griseum, which has only previously been documented in tuco-tucos (Ctenomys haigi, C. sociabilis), Syrian hamsters (Mesocricetus auratus) and naked mole-rats (Heterocephalus glaber). V1aR binding was present in the ventral pallidum, lateral septum, nucleus basalis, bed nucleus of the stria terminalis, hippocampus, medial amygdala, and anterior, ventromedial and dorsomedial hypothalamus. Marked individual differences in V1aR binding were noted in the cingulate cortex and several thalamic nuclei, remarkably similar to prairie voles. While pharmacological studies are needed to determine whether oxytocin and vasopressin are involved in pair-bond formation in this species, our results lay a foundation for future investigations into the role of these neuropeptides in Taiwan vole social behavior.

Behavioral and neurophysiological evidence that lateral paracapsular GABAergic synapses in the basolateral amygdala contribute to the acquisition and extinction of fear learning.

The lateral/basolateral amygdala (BLA) is crucial to the acquisition and extinction of Pavlovian fear conditioning, and synaptic plasticity in this region is considered to be a neural correlate of learned fear. We recently reported that activation of BLA ß3-adrenoreceptors (ß3-ARs) selectively enhances lateral paracapsular (LPC) feed-forward GABAergic inhibition onto BLA pyramidal neurons, and that intra-BLA infusion of a ß3-AR agonist reduces measures of unconditioned anxiety-like behavior. Here, we utilized a combination of behavioral and electrophysiological approaches to characterize the role of BLA LPCs in the acquisition of fear and extinction learning in adult male Long-Evans rats. We report that intra-BLA microinjection of ß3-AR agonists (BRL37344 or SR58611A, 1µg/0.5µL/side) prior to training fear conditioning or extinction blocks the expression of these behaviors 24h later. Furthermore,ex vivo low-frequency stimulation of the external capsule (LFS; 1Hz, 15min), which engages LPC synapses, induces LTP of BLA fEPSPs, while application of a ß3-AR agonist (SR58611A, 5µM) induces LTD of fEPSPs when combined with LFS. Interestingly, fEPSP LTP is not observed in recordings from fear conditioned animals, suggesting that fear learning may engage the same mechanisms that induce synaptic plasticity at this input. In support of this, we find that LFS produces LTD of inhibitory postsynaptic currents (iLTD) at LPC GABAergic synapses, and that this effect is also absent following fear conditioning. Taken together, these data provide preliminary evidence that modulation of LPC GABAergic synapses can influence the acquisition and extinction of fear learning and related synaptic plasticity in the BLA.

Adolescent social isolation increases anxiety-like behavior and ethanol intake and impairs fear extinction in adulthood: Possible role of disrupted noradrenergic signaling.

Alcohol use disorder, anxiety disorders, and post-traumatic stress disorder (PTSD) are highly comorbid, and exposure to chronic stress during adolescence may increase the incidence of these conditions in adulthood. Efforts to identify the common stress-related mechanisms driving these disorders have been hampered, in part, by a lack of reliable preclinical models that replicate their comorbid symptomatology. Prior work by us, and others, has shown that adolescent social isolation increases anxiety-like behaviors and voluntary ethanol consumption in adult male Long-Evans rats. Here we examined whether social isolation also produces deficiencies in extinction of conditioned fear, a hallmark symptom of PTSD. Additionally, as disrupted noradrenergic signaling may contribute to alcoholism, we examined the effect of anxiolytic medications that target noradrenergic signaling on ethanol intake following adolescent social isolation. Our results confirm and extend previous findings that adolescent social isolation increases anxiety-like behavior and enhances ethanol intake and preference in adulthood. Additionally, social isolation is associated with a significant deficit in the extinction of conditioned fear and a marked increase in the ability of noradrenergic therapeutics to decrease ethanol intake. These results suggest that adolescent social isolation not only leads to persistent increases in anxiety-like behaviors and ethanol consumption, but also disrupts fear extinction, and as such may be a useful preclinical model of stress-related psychopathology. Our data also suggest that disrupted noradrenergic signaling may contribute to escalated ethanol drinking following social isolation, thus further highlighting the potential utility of noradrenergic therapeutics in treating the deleterious behavioral sequelae associated with early life stress.

Cost-effective sampling of (137)Cs-derived net soil redistribution: part 2 - estimating the spatial mean change over time.

The caesium-137 ((137)Cs) technique for estimating net, time-integrated soil redistribution by the processes of wind, water and tillage is increasingly being used with repeated sampling to form a baseline to evaluate change over small (years to decades) timeframes. This interest stems from knowledge that since the 1950s soil redistribution has responded dynamically to different phases of land use change and management. Currently, there is no standard approach to detect change in (137)Cs-derived net soil redistribution and thereby identify the driving forces responsible for change. We outline recent advances in space-time sampling in the soil monitoring literature which provide a rigorous statistical and pragmatic approach to estimating the change over time in the spatial mean of environmental properties. We apply the space-time sampling framework, estimate the minimum detectable change of net soil redistribution and consider the information content and cost implications of different sampling designs for a study area in the Chinese Loess Plateau. Three phases (1954-1996, 1954-2012 and 1996-2012) of net soil erosion were detectable and attributed to well-documented historical change in land use and management practices in the study area and across the region. We recommend that the design for space-time sampling is considered carefully alongside cost-effective use of the spatial mean to detect and correctly attribute cause of change over time particularly across spatial scales of variation.