Carbon-Enhanced Metal-Poor Stars in the Inner and Outer Halo Components of the Milky Way

(Abridged) Carbon-enhanced metal-poor (CEMP) stars in the halo components of the Milky Way are explored, based on accurate determinations of the carbon-to-iron ([C/Fe]) abundance ratios and kinematic quantities for over 30000 calibration stars from the Sloan Digital Sky Survey (SDSS). Using our present criterion that low-metallicity stars exhibiting [C/Fe] ratios ("carbonicity") in excess of [C/Fe]$= +0.7$ are considered CEMP stars, the global frequency of CEMP stars in the halo system for \feh\ $< -1.5$ is 8%; for \feh\ $< -2.0$ it is 12%; for \feh\ $<-2.5$ it is 20%. We also confirm a significant increase in the level of carbon enrichment with declining metallicity, growing from $\sim +1.0$ at \feh\ $= -1.5$ to $\sim +1.7$ at \feh\ $= -2.7$. The nature of the carbonicity distribution function (CarDF) changes dramatically with increasing distance above the Galactic plane, $|$Z$|$. For $|$Z$|$ $< 5$ kpc, relatively few CEMP stars are identified. For distances $|$Z$|$ $> 5$ kpc, the CarDF exhibits a strong tail towards high values, up to [C/Fe] $>$ +3.0. We also find a clear increase in the CEMP frequency with $|$Z$|$. For stars with $-2.0 <$ [Fe/H] $< -$1.5, the frequency grows from 5% at $|$Z$|$ $\sim 2$ kpc to 10% at $|$Z$|$ $\sim 10$ kpc. For stars with [Fe/H] $< -$2.0, the frequency grows from 8% at $|$Z$|$ $\sim 2$ kpc to 25% at $|$Z$|$ $\sim 10$ kpc. For stars with $-2.0 <$ [Fe/H] $\sim +1.0$ for 0 kpc $<$ $|$Z$|$ $<$ 10 kpc, with little dependence on $|$Z$|$; for [Fe/H] $< -$2.0, $\sim +1.5$, again roughly independent of $|$Z$|$.Comment: Accepted for publication in the Astrophysical Journal, 32 pages, 15 figure

Roadmap on chalcogenide photonics

Alloys of sulfur, selenium and tellurium, often referred to as chalcogenide semiconductors, offer a highly versatile, compositionally-controllable material platform for a variety of passive and active photonic applications. They are optically nonlinear, photoconductive materials with wide transmission windows that present various high- and low-index dielectric, low-epsilon and plasmonic properties across ultra-violet, visible and infrared frequencies, in addition to an, non-volatile, electrically/optically induced switching capability between phase states with markedly different electromagnetic properties. This roadmap collection presents an in-depth account of the critical role that chalcogenide semiconductors play within various traditional and emerging photonic technology platforms. The potential of this field going forward is demonstrated by presenting context and outlook on selected socio-economically important research streams utilizing chalcogenide semiconductors. To this end, this roadmap encompasses selected topics that range from systematic design of material properties and switching kinetics to device-level nanostructuring and integration within various photonic system architectures

MAIT cells launch a rapid, robust and distinct hyperinflammatory response to bacterial superantigens and quickly acquire an anergic phenotype that impedes their cognate antimicrobial function: Defining a novel mechanism of superantigen-induced immunopathology and immunosuppression

Superantigens (SAgs) are potent exotoxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They target a large fraction of T cell pools to set in motion a "cytokine storm" with severe and sometimes life-threatening consequences typically encountered in toxic shock syndrome (TSS). Given the rapidity with which TSS develops, designing timely and truly targeted therapies for this syndrome requires identification of key mediators of the cytokine storm's initial wave. Equally important, early host responses to SAgs can be accompanied or followed by a state of immunosuppression, which in turn jeopardizes the host's ability to combat and clear infections. Unlike in mouse models, the mechanisms underlying SAg-associated immunosuppression in humans are ill-defined. In this work, we have identified a population of innate-like T cells, called mucosa-associated invariant T (MAIT) cells, as the most powerful source of pro-inflammatory cytokines after exposure to SAgs. We have utilized primary human peripheral blood and hepatic mononuclear cells, mouse MAIT hybridoma lines, HLA-DR4-transgenic mice, MAIThighHLA-DR4+ bone marrow chimeras, and humanized NOD-scid IL-2Rγnull mice to demonstrate for the first time that: i) mouse and human MAIT cells are hyperresponsive to SAgs, typified by staphylococcal enterotoxin B (SEB); ii) the human MAIT cell response to SEB is rapid and far greater in magnitude than that launched by unfractionated conventional T, invariant natural killer T (iNKT) or γδ T cells, and is characterized by production of interferon (IFN)-γ, tumor necrosis factor (TNF)-α and interleukin (IL)-2, but not IL-17A; iii) high-affinity MHC class II interaction with SAgs, but not MHC-related protein 1 (MR1) participation, is required for MAIT cell activation; iv) MAIT cell responses to SEB can occur in a T cell receptor (TCR) Vβ-specific manner but are largely contributed by IL-12 and IL-18; v) as MAIT cells are primed by SAgs, they also begin to develop a molecular signature consistent with exhaustion and failure to participate in antimicrobial defense. Accordingly, they upregulate lymphocyte-activation gene 3 (LAG-3), T cell immunoglobulin and mucin-3 (TIM-3), and/or programmed cell death-1 (PD-1), and acquire an anergic phenotype that interferes with their cognate function against Klebsiella pneumoniae and Escherichia coli; vi) MAIT cell hyperactivation and anergy co-utilize a signaling pathway that is governed by p38 and MEK1/2. Collectively, our findings demonstrate a pathogenic, rather than protective, role for MAIT cells during infection. Furthermore, we propose a novel mechanism of SAg-associated immunosuppression in humans. MAIT cells may therefore provide an attractive therapeutic target for the management of both early and late phases of severe SAg-mediated illnesses

Formin homology 2 domains occur in multiple contexts in angiosperms

BACKGROUND: Involvement of conservative molecular modules and cellular mechanisms in the widely diversified processes of eukaryotic cell morphogenesis leads to the intriguing question: how do similar proteins contribute to dissimilar morphogenetic outputs. Formins (FH2 proteins) play a central part in the control of actin organization and dynamics, providing a good example of evolutionarily versatile use of a conserved protein domain in the context of a variety of lineage-specific structural and signalling interactions. RESULTS: In order to identify possible plant-specific sequence features within the FH2 protein family, we performed a detailed analysis of angiosperm formin-related sequences available in public databases, with particular focus on the complete Arabidopsis genome and the nearly finished rice genome sequence. This has led to revision of the current annotation of half of the 22 Arabidopsis formin-related genes. Comparative analysis of the two plant genomes revealed a good conservation of the previously described two subfamilies of plant formins (Class I and Class II), as well as several subfamilies within them that appear to predate the separation of monocot and dicot plants. Moreover, a number of plant Class II formins share an additional conserved domain, related to the protein phosphatase/tensin/auxilin fold. However, considerable inter-species variability sets limits to generalization of any functional conclusions reached on a single species such as Arabidopsis. CONCLUSIONS: The plant-specific domain context of the conserved FH2 domain, as well as plant-specific features of the domain itself, may reflect distinct functional requirements in plant cells. The variability of formin structures found in plants far exceeds that known from both fungi and metazoans, suggesting a possible contribution of FH2 proteins in the evolution of the plant type of multicellularity

The role of GDNF family ligand signalling in the differentiation of sympathetic and dorsal root ganglion neurons

The diversity of neurons in sympathetic ganglia and dorsal root ganglia (DRG) provides intriguing systems for the analysis of neuronal differentiation. Cell surface receptors for the GDNF family ligands (GFLs) glial cell-line-derived neurotrophic factor (GDNF), neurturin and artemin, are expressed in subpopulations of these neurons prompting the question regarding their involvement in neuronal subtype specification. Mutational analysis in mice has demonstrated the requirement for GFL signalling during embryonic development of cholinergic sympathetic neurons as shown by the loss of expression from the cholinergic gene locus in ganglia from mice deficient for ret, the signal transducing subunit of the GFL receptor complex. Analysis in mutant animals and transgenic mice overexpressing GFLs demonstrates an effect on sensitivity to thermal and mechanical stimuli in DRG neurons correlating at least partially with the altered expression of transient receptor potential ion channels and acid-sensitive cation channels. Persistence of targeted cells in mutant ganglia suggests that the alterations are caused by differentiation effects and not by cell loss. Because of the massive effect of GFLs on neurite outgrowth, it remains to be determined whether GFL signalling acts directly on neuronal specification or indirectly via altered target innervation and access to other growth factors. The data show that GFL signalling is required for the specification of subpopulations of sensory and autonomic neurons. In order to comprehend this process fully, the role of individual GFLs, the transduction of the GFL signals, and the interplay of GFL signalling with other regulatory pathways need to be deciphered

P2 receptors and chronic pain

There is abundant evidence that extracellular ATP and other nucleotides have an important role in pain signaling at both the periphery and in the CNS. The focus of attention now is on the possibility that endogenous ATP and its receptor system might be activated in chronic pathological pain states, particularly in neuropathic and inflammatory pain. Neuropathic pain is often a consequence of nerve injury through surgery, bone compression, diabetes or infection. This type of pain can be so severe that even light touching can be intensely painful; unfortunately, this state is generally resistant to currently available treatments. In this review, we summarize the role of ATP receptors, particularly the P2X4, P2X3 and P2X7 receptors, in neuropathic and inflammatory pain. The expression of P2X4 receptors in the spinal cord is enhanced in spinal microglia after peripheral nerve injury, and blocking pharmacologically and suppressing molecularly P2X4 receptors produce a reduction of the neuropathic pain behaviour. Understanding the key roles of these ATP receptors may lead to new strategies for the management of intractable chronic pain

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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