The maintenance of immune homeostasis requires regulatory T cells (Tregs). Given their intrinsic self-reactivity, Tregs must stably maintain a suppressive phenotype to avoid autoimmunity. We report ...that impaired expression of the transcription factor (TF) Helios by FoxP3+ CD4 and Qa-1–restricted CD8 Tregs results in defective regulatory activity and autoimmunity in mice. Helios-deficient Tregs develop an unstable phenotype during inflammatory responses characterized by reduced FoxP3 expression and increased effector cytokine expression secondary to diminished activation of the STAT5 pathway. CD8 Tregs also require Helios-dependent STAT5 activation for survival and to prevent terminal T cell differentiation. The definition of Helios as a key transcription factor that stabilizes Tregs in the face of inflammatory responses provides a genetic explanation for a core property of Tregs.
X-ray observations of transiently accreting neutron stars during quiescence provide information about the structure of neutron star crusts and the properties of dense matter. Interpretation of the ...observational data requires an understanding of the nuclear reactions that heat and cool the crust during accretion and define its nonequilibrium composition. We identify here in detail the typical nuclear reaction sequences down to a depth in the inner crust where the mass density is using a full nuclear reaction network for a range of initial compositions. The reaction sequences differ substantially from previous work. We find a robust reduction of crust impurity at the transition to the inner crust regardless of initial composition, though shell effects can delay the formation of a pure crust somewhat to densities beyond . This naturally explains the small inner crust impurity inferred from observations of a broad range of systems. The exception are initial compositions with A ≥ 102 nuclei, where the inner crust remains impure with an impurity parameter of Qimp 20 owing to the N = 82 shell closure. In agreement with previous work, we find that nuclear heating is relatively robust and independent of initial composition, while cooling via nuclear Urca cycles in the outer crust depends strongly on initial composition. This work forms a basis for future studies of the sensitivity of crust models to nuclear physics and provides profiles of composition for realistic crust models.
The European Union's position on “one China” has stood since the establishment of diplomatic relations with the People's Republic of China (PRC) in 1975. As a union of distinct member states, the ...nature of the European Union's (EU) foreign policymaking complicates efforts to maintain coherent common positions. Its effective “one China policy” (and those of its member states) is no exception. In recent years, the edges of the bloc's long-standing policy have started to fray as the EU–PRC relationship has become more fraught and many member states have sought to deepen their effective, if “unofficial,” engagement with Taiwan. I explore these changes to the EU's effective “one China policy” by employing a subsystems framework, starting from the position that the EU has foreign policies (rather than a singular policy) created through three subsystems. Through the Normative Power Europe lens, I explore the extent to which the actors pulling at these “threads” at the edges of the EU's policy are motivated by normative concerns. I argue that the “fraying” of the EU's “one China policy” is not the result of a conscious decision by the EU as a collective normative actor but stems from shifting preferences within the national and supranational subsystems.
Anderson localisation -the inhibition of wave propagation in disordered media- is a surprising interference phenomenon which is particularly intriguing in two-dimensional (2D) systems. While an ...ideal, non-interacting 2D system of infinite size is always localised, the localisation length-scale may be too large to be unambiguously observed in an experiment. In this sense, 2D is a marginal dimension between one-dimension, where all states are strongly localised, and three-dimensions, where a well-defined phase transition between localisation and delocalisation exists as the energy is increased. Here, we report the results of an experiment measuring the 2D transport of ultracold atoms between two reservoirs, which are connected by a channel containing pointlike disorder. The design overcomes many of the technical challenges that have hampered observation of localisation in previous works. We experimentally observe exponential localisation in a 2D ultracold atom system.
Here we extend this study using the larger 9 deg super(2) NOAO Deep Wide-Field Survey Bootes field which also has considerably deeper WISE observations than the COSMOS field, and find that this ...simple color cut significantly loses reliability at fainter fluxes. We define a modified selection criterion combining the W1-W2 color and the W2 magnitude to provide highly reliable or highly complete AGN samples for fainter WISE sources. In particular, we define a color-magnitude cut that finds 130 + or - 4 deg super(-2) AGN candidates for W2 < 17.11 with 90% reliability. We study the distribution of reddening in the AGN sample and discuss a formalism to account for sample incompleteness based on the step-wise maximum-likelihood method of Efstathiou et al. The resulting dust obscuration distributions depend strongly on AGN luminosity, consistent with the trend expected for a receding torus. The distribution of obscuration values suggests that dust in the torus is present as both a diffuse medium and in optically thick clouds.
Paired catchment studies have been widely used as a means of determining the magnitude of water yield changes resulting from changes in vegetation. This review focuses on the use of paired catchment ...studies for determining the changes in water yield at various time scales resulting from permanent changes in vegetation. The review considers long term annual changes, adjustment time scales, the seasonal pattern of flows and changes in both annual and seasonal flow duration curves. The paired catchment studies reported in the literature have been divided into four broad categories: afforestation experiments, deforestation experiments, regrowth experiments and forest conversion experiments. Comparisons between paired catchment results and a mean annual water balance model are presented and show good agreement between the two methodologies. The results highlight the potential underestimation of water yield changes if regrowth experiments are used to predict the likely impact of permanent alterations to a catchment's vegetation. An analysis of annual water yield changes from afforestation, deforestation and regrowth experiments demonstrates that the time taken to reach a new equilibrium under permanent land use change varies considerably. Deforestation experiments reach a new equilibrium more quickly than afforestation experiments. The review of papers reporting seasonal changes in water yield highlights the proportionally larger impact on low flows. Flow duration curve comparison provides a potential means of gaining a greater understanding of the impact of vegetation on the distribution of daily flows.
Energy intake (EI) and physical activity energy expenditure (PAEE) are key modifiable determinants of energy balance, traditionally assessed by self-report despite its repeated demonstration of ...considerable inaccuracies. We argue here that it is time to move from the common view that self-reports of EI and PAEE are imperfect, but nevertheless deserving of use, to a view commensurate with the evidence that self-reports of EI and PAEE are so poor that they are wholly unacceptable for scientific research on EI and PAEE. While new strategies for objectively determining energy balance are in their infancy, it is unacceptable to use decidedly inaccurate instruments, which may misguide health-care policies, future research and clinical judgment. The scientific and medical communities should discontinue reliance on self-reported EI and PAEE. Researchers and sponsors should develop objective measures of energy balance.
Evolutionary origins of derived morphologies ultimately stem from changes in protein structure, gene regulation, and gene content. A well-assembled, annotated reference genome is a central resource ...for pursuing these molecular phenomena underlying phenotypic evolution. We explored the genome of the Gulf pipefish (Syngnathus scovelli), which belongs to family Syngnathidae (pipefishes, seahorses, and seadragons). These fishes have dramatically derived bodies and a remarkable novelty among vertebrates, the male brood pouch.
We produce a reference genome, condensed into chromosomes, for the Gulf pipefish. Gene losses and other changes have occurred in pipefish hox and dlx clusters and in the tbx and pitx gene families, candidate mechanisms for the evolution of syngnathid traits, including an elongated axis and the loss of ribs, pelvic fins, and teeth. We measure gene expression changes in pregnant versus non-pregnant brood pouch tissue and characterize the genomic organization of duplicated metalloprotease genes (patristacins) recruited into the function of this novel structure. Phylogenetic inference using ultraconserved sequences provides an alternative hypothesis for the relationship between orders Syngnathiformes and Scombriformes. Comparisons of chromosome structure among percomorphs show that chromosome number in a pipefish ancestor became reduced via chromosomal fusions.
The collected findings from this first syngnathid reference genome open a window into the genomic underpinnings of highly derived morphologies, demonstrating that de novo production of high quality and useful reference genomes is within reach of even small research groups.
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