Pituitary Adenylate-Cyclase Activating Polypeptide Regulates Hunger- and Palatability-Induced Binge Eating

While pituitary adenylate cyclase activating polypeptide (PACAP) signaling in the hypothalamic ventromedial nuclei (VMN) has been shown to regulate feeding, a challenge in unmasking a role for this peptide in obesity is that excess feeding can involve numerous mechanisms including homeostatic (hunger) and hedonic-related (palatability) drives. In these studies, we first isolated distinct feeding drives by developing a novel model of binge behavior in which homeostatic-driven feeding was temporally separated from feeding driven by food palatability. We found that stimulation of the VMN, achieved by local microinjections of AMPA, decreased standard chow consumption in food-restricted rats (e.g., homeostatic feeding); surprisingly, this manipulation failed to alter palatable food consumption in satiated rats (e.g., hedonic feeding). In contrast, inhibition of the nucleus accumbens (NAc), through local microinjections of GABA receptor agonists baclofen and muscimol, decreased hedonic feeding without altering homeostatic feeding. PACAP microinjections produced the site-specific changes in synaptic transmission needed to decrease feeding via VMN or NAc circuitry. PACAP into the NAc mimicked the actions of GABA agonists by reducing hedonic feeding without altering homeostatic feeding. In contrast, PACAP into the VMN mimicked the actions of AMPA by decreasing homeostatic feeding without affecting hedonic feeding. Slice electrophysiology recordings verified PACAP excitation of VMN neurons and inhibition of NAc neurons. These data suggest that the VMN and NAc regulate distinct circuits giving rise to unique feeding drives, but that both can be regulated by the neuropeptide PACAP to potentially curb excessive eating stemming from either drive

Mammal communities are larger and more diverse in moderately developed areas

Developed areas are thought to have low species diversity, low animal abundance, few native predators, and thus low resilience and ecological function. Working with citizen scientist volunteers to survey mammals at 1427 sites across two development gradients (wild-rural-exurban- suburban-urban) and four plot types (large forests, small forest fragments, open areas and residential yards) in the eastern US, we show that developed areas actually had significantly higher or statistically similar mammalian occupancy, relative abundance, richness and diversity compared to wild areas. However, although some animals can thrive in suburbia, conservation of wild areas and preservation of green space within cities are needed to protect sensitive species and to give all species the chance to adapt and persist in the Anthropocene. DOI: https://doi.org/10.7554/eLife.38012.00

Measuring psychological pain: psychometric analysis of the Orbach and Mikulincer Mental Pain Scale

Background: Suicide is a public health concern, with an estimated 1 million individuals dying each year worldwide. Individual psychological pain is believed to be a contributing motivating factor. Therefore, establishing a psychometrically sound tool to adequately measure psychological pain is important. The Orbach and Mikulincer Mental Pain Scale (OMMP) has been proposed; however, previous psychometric analysis on the OMMP has not yielded a consistent scale structure, and the internal consistency of the subscales has not met recommended values. Therefore, the primary purpose of this study was to assess the psychometric properties of the OMMP in a diverse sample. Methods: A confirmatory factor analysis (CFA) on the 9-factor, 44-item OMMP was conducted on the full sample (n = 1151). Because model fit indices were not met, an exploratory factor analysis (EFA) was conducted on a random subset of the data (n = 576) to identify a more parsimonious structure. The EFA structure was then tested in a covariance model in the remaining subset of participants (n = 575). Multigroup invariance testing was subsequently performed to examine psychometric properties of the refined scale. Results: The CFA of the original 9-factor, 44-item OMMP did not meet recommended model fit recommendations. The EFA analysis results revealed a 3-factor, 9-item scale (i.e., OMMP-9). The covariance model of the OMMP-9 indicated further refinement was necessary. Multigroup invariance testing conducted on the final 3-factor, 8-item scale (i.e., OMMP-8) across mental health diagnoses, sex, injury status, age, activity level, and athlete classification met all criteria for invariance. Conclusions: The 9-factor, 44-item OMMP does not meet recommended measurement criteria and should not be recommended for use in research and clinical practice in its current form. The refined OMMP-8 may be a more viable option to use; however, more research should be completed prior to adoption

A New Obesity Model Reveals the Hypophagic Properties of PACAP Involve the Regulation of Homeostatic Feeding in the Ventromedial Hypothalamic Nucleus and Hedonic Feeding in the Nucleus Accumbens

Binge eating in humans is a complex disorder that often involves discrete, compulsive feeding sessions of highly palatable foods even in the absence of a deprivation state or hunger. Binging can be effectively modeled in rodents by providing subjects with limited access to a palatable food source (Western Diet; WD) as an adjunct to ad lib access to normal chow (Standard Chow; SC). Although this design recapitulates several fundamental characteristics observed in binge eating disorder, the binge eating observed in this paradigm is likely a product of both hedonic and homeostatic drives with the need to balance energy stores still present. To isolate these feeding drives, we have developed a novel feeding regimen that modifies the classic limited access binge model to effectively delineate and separate homeostatic feeding from motivational feeding. This is achieved by entraining male Sprague-Dawley rats to a restricted feeding schedule (two hours per day) of SC followed by a short 15 minute limited access meal of either SC or WD (Restrict Fed-Limited Access; RFLA). The RFLA paradigm allows for the examination of pituitary adenylate-cyclase activating polypeptide (PACAP) on palatable food consumption in a fully satiated subject. PACAP has previously been shown to suppress feeding behavior when injected into the hypothalamus. In the current study, PACAP injected into the ventromedial hypothalamic nuclei (VMN) suppressed the two hour homeostatic SC meal, but not the subsequent 15 minute limited access meal of WD. By contrast, PACAP bilaterally administered into the nucleus accumbens (NAc) produced the opposite effect with PACAP suppressing the consumption of WD but not SC. Thus, PACAP mediated signaling in the VMN appears to be involved in homeostatic regulation of energy stores, whereas PACAP signaling in the NAc regulates feeding driven by palatability or hedonic qualities

No Change in Perceptual or Chronotropic Outcome When Altering Preferred Step Frequency for a Short Duration

IIntroduction: Millions of individuals incorporate jogging into their physical activity routines as a leisurely pursuit and as a way to achieve positive health outcomes. People appear to choose jogging speed and the associated step frequency on pure, natural preference. Understandably, kinesthetics are important, but another important underlying factor is metabolic cost. The purpose of this work was to investigate if preferred step frequency (at a preferred jogging pace) also minimizes perceived effort (Borg Rating of Perceived Exertion, 6-20; RPE) and chronotropic stress (heart rate; HR) during a ten-minute activity bout when compared with step frequencies altered by 5%. Methods: Recreationally-trained male subjects underwent two testing visits. The first visit was used to establish RPE and HR responses during a 10-minute jogging activity at preferred speed and step frequency. On a subsequent visit, between two and four days later, with preferred speed maintained, subjects were guided by metronome to strike at either 95% or 105% of their preferred step frequency. The 10-minute runs were randomized, crossed-over, and separated by 20 minutes. RPE and HR were analyzed by repeated measures ANOVA. Results: Fourteen subjects (age: 21.1 ± 0.95; body mass index: 23.2 ± 2.5) enrolled. Preferred jogging speed (speed. 6.4 ± 1.0 miles per hour; 10.2 ± 1.6 kilometers per hour) and step frequency (steps. 161.2 ± 10.3 steps/minute) were determined at the first visit, along with RPE (11.3 ± 1.7) and HR (166.4 ± 12.7). At the second visit, preferred speed was maintained while the frequency of foot-strike was altered. Neither differences in RPE (p = 0.252; 11.3 ± 1.7, 11.6 ± 1.9, 11.8 ± 1.5) nor HR (p = 0.547; 166.4 ± 12.7, 164.7 ± 14.9, 165.2 ± 15.3) were different when comparing the preferred, 95%, and 105% step frequency trials, respectively. Although anecdotal, some subjects verbalized displeasure with the change in pace and most all appeared to markedly alter the initial foot strike phase of the gait to meet the directed foot strike tempo. Discussion: Our data must be interpreted cautiously. While altering step frequency by 5% for a short duration does not appear to alter an individual’s RPE or HR appreciably, the result during longer duration activity may not be the same. In addition, the implications for biomechanical loading and metabolic cost were not presently investigated

The Atacama Cosmology Telescope: the stellar content of galaxy clusters selected using the Sunyaev-Zel'dovich effect

We present a first measurement of the stellar mass component of galaxy clusters selected via the Sunyaev-Zel'dovich (SZ) effect, using 3.6 um and 4.5 um photometry from the Spitzer Space Telescope. Our sample consists of 14 clusters detected by the Atacama Cosmology Telescope (ACT), which span the redshift range 0.27 < z < 1.07 (median z = 0.50), and have dynamical mass measurements, accurate to about 30 per cent, with median M500 = 6.9 x 10^{14} MSun. We measure the 3.6 um and 4.5 um galaxy luminosity functions, finding the characteristic magnitude (m*) and faint-end slope (alpha) to be similar to those for IR-selected cluster samples. We perform the first measurements of the scaling of SZ-observables (Y500 and y0) with both brightest cluster galaxy (BCG) stellar mass and total cluster stellar mass (M500star). We find a significant correlation between BCG stellar mass and Y500 (E(z)^{-2/3} DA^2 Y500 ~ M*^{1.2 +/- 0.6}), although we are not able to obtain a strong constraint on the slope of the relation due to the small sample size. Additionally, we obtain E(z)^{-2/3} DA^2 Y500 ~ M500star^{1.0 +/- 0.6} for the scaling with total stellar mass. The mass fraction in stars spans the range 0.006-0.034, with the second ranked cluster in terms of dynamical mass (ACT-CL J0237-4939) having an unusually low total stellar mass and the lowest stellar mass fraction. For the five clusters with gas mass measurements available in the literature, we see no evidence for a shortfall of baryons relative to the cosmic mean value.Comment: Accepted for publication in MNRAS; 12 pages, 10 figure

Avalanches on a conical bead pile: scaling with tuning parameters

Uniform spherical beads were used to explore the behavior of a granular system near its critical angle of repose on a conical bead pile. We found two tuning parameters that could take the system to a critical point where a simple power-law described the avalanche size distribution as predicted by self-organized criticality, which proposed that complex dynamical systems self-organize to a critical point without need for tuning. Our distributions were well described by a simple power-law with the power {\tau} = 1.5 when dropping beads slowly onto the apex of a bead pile from a small height. However, we could also move the system from the critical point using either of two tuning parameters: the height from which the beads fell onto the top of the pile or the region over which the beads struck the pile. As the drop height increased, the system did not reach the critical point yet the resulting distributions were independent of the bead mass, coefficient of friction, or coefficient of restitution. All our apex-dropping distributions for any type of bead (glass, stainless steel, zirconium) showed universality by scaling onto a common curve with {\tau} = 1.5 and {\sigma} = 1.0, where 1/{\sigma} is the power of the tuning parameter. From independent calculations using the moments of the distribution, we find values for {\tau} = 1.6 \pm 0.1 and {\sigma} = 0.91 \pm 0.15. When beads were dropped across the surface of the pile instead of solely on the apex, then the system also moved from the critical point and again the avalanche size distributions fell on a common curve when scaled similarly using the same values of {\tau} and {\sigma}. We also observed that an hcp structure on the base of the pile caused an emergent structure in the pile that had six faces with some fcc or hcp structure.Comment: 8 pages, 6 figures; submitted to Granular Matter; Reformatted into LaTeX from Word; Fixed typo in uncertainty of tau; Rearranged two paragraphs to improve flo

Multi-Messenger Gravitational Wave Searches with Pulsar Timing Arrays: Application to 3C66B Using the NANOGrav 11-year Data Set

When galaxies merge, the supermassive black holes in their centers may form binaries and, during the process of merger, emit low-frequency gravitational radiation in the process. In this paper we consider the galaxy 3C66B, which was used as the target of the first multi-messenger search for gravitational waves. Due to the observed periodicities present in the photometric and astrometric data of the source of the source, it has been theorized to contain a supermassive black hole binary. Its apparent 1.05-year orbital period would place the gravitational wave emission directly in the pulsar timing band. Since the first pulsar timing array study of 3C66B, revised models of the source have been published, and timing array sensitivities and techniques have improved dramatically. With these advances, we further constrain the chirp mass of the potential supermassive black hole binary in 3C66B to less than $(1.65\pm0.02) \times 10^9~{M_\odot}$ using data from the NANOGrav 11-year data set. This upper limit provides a factor of 1.6 improvement over previous limits, and a factor of 4.3 over the first search done. Nevertheless, the most recent orbital model for the source is still consistent with our limit from pulsar timing array data. In addition, we are able to quantify the improvement made by the inclusion of source properties gleaned from electromagnetic data to `blind' pulsar timing array searches. With these methods, it is apparent that it is not necessary to obtain exact a priori knowledge of the period of a binary to gain meaningful astrophysical inferences.Comment: 14 pages, 6 figures. Accepted by Ap

Host-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice [preprint]

The outcome of an encounter with Mycobacterium tuberculosis (Mtb) depends on the pathogen’s ability to adapt to the heterogeneous immune response of the host. Understanding this interplay has proven difficult, largely because experimentally tractable small animal models do not recapitulate the heterogenous disease observed in natural infections. We leveraged the genetically diverse Collaborative Cross (CC) mouse panel in conjunction with a library of Mtb mutants to associate bacterial genetic requirements with host genetics and immunity. We report that CC strains vary dramatically in their susceptibility to infection and represent reproducible models of qualitatively distinct immune states. Global analysis of Mtb mutant fitness across the CC panel revealed that a large fraction of the pathogen’s genome is necessary for adaptation to specific host microenvironments. Both immunological and bacterial traits were associated with genetic variants distributed across the mouse genome, elucidating the complex genetic landscape that underlies host-pathogen interactions in a diverse population