Unveiling the Distinct Formation Pathways of the Inner and Outer Discs of the Milky Way with Bayesian Machine Learning

We develop a Bayesian Machine Learning framework called BINGO (Bayesian INference for Galactic archaeOlogy) centred around a Bayesian neural network. After being trained on the APOGEE and \emph{Kepler} asteroseismic age data, BINGO is used to obtain precise relative stellar age estimates with uncertainties for the APOGEE stars. We carefully construct a training set to minimise bias and apply BINGO to a stellar population that is similar to our training set. We then select the 17,305 stars with ages from BINGO and reliable kinematic properties obtained from \textit{Gaia} DR2. By combining the age and chemo-kinematical information, we dissect the Galactic disc stars into three components, namely, the thick disc (old, high-[$\alpha$/Fe], [$\alpha$/Fe] $\gtrsim$ 0.12), the thin disc (young, low-[$\alpha$/Fe]) and the Bridge, which is a region between the thick and thin discs. Our results indicate that the thick disc formed at an early epoch only in the inner region, and the inner disc smoothly transforms to the thin disc. We found that the outer disc follows a different chemical evolution pathway from the inner disc. The outer metal-poor stars only start forming after the compact thick disc phase has completed and the star-forming gas disc extended outwardly with metal-poor gas accretion. We found that in the Bridge region the range of [Fe/H] becomes wider with decreasing age, which suggests that the Bridge region corresponds to the transition phase from the smaller chemically well-mixed thick to a larger thin disc with a metallicity gradient.Comment: 11 pages, 11 figures, accepted in MNRA

Central Serotonin and Melanocortin Pathways Regulating Energy Homeostasis

It is now established that the hypothalamus is essential in coordinating endocrine, autonomic, and behavioral responses to changes in energy availability. However, the interaction of key peptides, neuropeptides, and neurotransmitters systems within the hypothalamus has yet to be delineated. Recently, we investigated the mechanisms through which serotonergic (5-hydroxytryptamine, 5-HT) systems recruit leptin-responsive hypothalamic pathways, such as the melanocortin systems, to affect energy balance. Through a combination of functional neuroanatomy, feeding, and electrophysiology studies in rodents, we found that 5-HT drugs require functional melanocortin pathways to exert their effects on food intake. Specifically, we observed that anorectic 5-HT drugs activate pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (Arc). We provide evidence that the serotonin 2C receptor (5-HT2CR) is expressed on POMC neurons and contributes to this effect. Finally, we found that 5-HT drug-induced hypophagia is attenuated by pharmalogical or genetic blockade of downstream melanocortin 3 and 4 receptors. We review candidate brain regions expressing melanocortin 3 and 4 receptors that play a role in energy balance. A model is presented in which the activation of the melanocortin system is downstream of 5-HT and is necessary to produce the complete anorectic effect of 5-HT drugs. The data reviewed in this paper incorporate the central 5-HT system to the growing list of metabolic signals that converge on melanocortin neurons in the hypothalamus

Food Acceptability in Field Studies with US Army Men and Women: Relationship with Food Intake and Food Choice After Repeated Exposures

Laboratory data with single exposures showed that palatability has a positive relationship with food intake. The question addressed in this study is whether this relationship also holds over repeated exposures in non-laboratory contexts in more natural environments. The data were collected in four field studies, lasting 4–11 days with 307 US Army men and 119 Army women, and comprised 5791 main meals and 8831 snacks in total. Acceptability was rated on the nine point hedonic scale, and intake was registered in units of 1/4, 1/2, 3/4, or 1 or more times of the provided portion size. Correlation coefficients between individual acceptability ratings and intakes varied from 0.22 to 0.62 for the main meals (n=193–2267), and between 0.13 and 0.56 for the snacks (n=304–2967). The likelihood of choosing a meal for the second time was positively related to the acceptability rating of the meal when it was consumed for the first time. The results reinforce the importance of liking in food choice and food intake/choice behavior. However, the magnitude of the correlation coefficients between acceptability ratings and food intake suggest that environmental factors also have an important role in determining intake and choice

Lineage Diversion of T Cell Receptor Transgenic Thymocytes Revealed by Lineage Fate Mapping

Background: The binding of the T cell receptor (TCR) to major histocompatibility complex (MHC) molecules in the thymus determines fates of $TCR\alpha\beta$ lymphocytes that subsequently home to secondary lymphoid tissue. TCR transgenic models have been used to study thymic selection and lineage commitment. Most TCR transgenic mice express the rearranged $TCR\alpha\beta$ prematurely at the double negative stage and abnormal TCRαβ populations of T cells that are not easily detected in non-transgenic mice have been found in secondary lymphoid tissue of TCR transgenic mice. Methodology and Principal Findings: To determine developmental pathways of TCR-transgenic thymocytes, we used Cre-LoxP-mediated fate mapping and show here that premature expression of a transgenic $TCR\alpha\beta$ diverts some developing thymocytes to a developmental pathway which resembles that of gamma delta cells. We found that most peripheral T cells with the HY-TCR in male mice have bypassed the RORγt-positive $CD4^{+}8^{+}$ (double positive, DP) stage to accumulate either as $CD4^{-}8^{-}$ (double negative, DN) or as $CD8\alpha^{+}$ T cells in lymph nodes or gut epithelium. Likewise, DN $TCR\alpha\beta$ cells in lymphoid tissue of female mice were not derived from DP thymocytes. Conclusion: The results further support the hypothesis that the premature expression of the $TCR\alpha\beta$ can divert DN thymocytes into gamma delta lineage cells

Equity or Efficiency? Explaining Public Officials' Values

This article analyzes the positions of top public officials on an equity-efficiency trade-off and the determinants of those positions. It uses data from a survey across 14 European countries. The results show that differences in public officials' positions on equity-efficiency are related to the context in which they work and to their personal background. Officials at the top of the hierarchy and those with a business or economics education are more oriented toward efficiency. Additionally, results show important differences associated with country administrative culture, including a stronger equity orientation in Scandinavian countries, and a stronger efficiency orientation in Southern European countries. The positions of public officials reflect those held by citizens in their country, confirming the contextualized nature of administrative values. This article contributes to understanding the determinants of public officials' dominant values

Interleukin 2 Receptor Signaling Regulates the Perforin Gene through Signal Transducer and Activator of Transcription (Stat)5 Activation of Two Enhancers

Optimal T cell differentiation into effector cells with specialized functions requires the participation of cytokine receptor signals. In T helper cells, this process is controlled by chromatin changes and distal and proximal regulatory elements as well as specific transcription factors. Analogous events during cytotoxic T lymphocyte (CTL) differentiation remain to be identified. This process is known, however, to be crucially regulated by interleukin (IL)-2 receptor (R) signals. It is accompanied by the induction of perforin expression via a mechanism that does not entail proximal regulatory elements. In this report, transgenically expressed human perforin gene locus DNAs demonstrate that IL-2R signals target two IL-2–dependent enhancers ∼15 and 1 kilobase upstream of the promoter. The most distal enhancer may also respond to TCR signals. In transient transfections, both enhancers required two identically spaced Stat-like elements for their activation, which was abolished by expression of a dominant negative signal transducer and activator of transcription (Stat)5 molecule, whereas a constitutively active Stat5 molecule bypassed the requirement for IL-2R signals. These results provide a molecular explanation for the activation of the perforin gene during CTL differentiation and complement the analysis of animals deficient in the activation of the IL-2R Stat signaling pathway by establishing perforin as a target gene