Tidal Streams as Probes of the Galactic Potential

We explore the use of tidal streams from Galactic satellites to recover the potential of the Milky Way. Our study is motivated both by the discovery of the first lengthy stellar stream in the halo (\cite{it98}) and by the prospect of measuring proper motions of stars brighter than 20th magnitude in such a stream with an accuracy of $\sim 4\mu as/$yr, as will be possible with the Space Interferometry Mission (SIM). We assume that the heliocentric radial velocities of these stars can be determined from supporting ground-based spectroscopic surveys, and that the mass and phase-space coordinates of the Galactic satellite with which they are associated will also be known to SIM accuracy. Using results from numerical simulations as trial data sets, we find that, if we assume the correct form for the Galactic potential, we can predict the distances to the stars as a consequence of the narrow distribution of energy expected along the streams. We develop an algorithm to evaluate the accuracy of any adopted potential by requiring that the satellite and stars recombine within a Galactic lifetime when their current phase-space coordinates are integrated backwards. When applied to a four-dimensional grid of triaxial logarithmic potentials, with varying circular velocities, axis ratios and orientation of the major-axis in the disk plane, the algorithm can recover the parameters used for the Milky Way in a simulated data set to within a few percent using only 100 stars in a tidal stream.Comment: Revised version - original algorithm generalised to be applicable to any potential shape. LaTeX, 12 pages including 3 figures. To be published in ApJ Letter

Tracing Galaxy Formation with Stellar Halos I: Methods

If the favored hierarchical cosmological model is correct, then the Milky Way system should have accreted ~100-200 luminous satellite galaxies in the past \~12 Gyr. We model this process using a hybrid semi-analytic plus N-body approach which distinguishes explicitly between the evolution of light and dark matter in accreted satellites. This distinction is essential to our ability to produce a realistic stellar halo, with mass and density profile much like that of our own Galaxy, and a surviving satellite population that matches the observed number counts and structural parameter distributions of the satellite galaxies of the Milky Way. Our model stellar halos have density profiles which typically drop off with radius faster than those of the dark matter. They are assembled from the inside out, with the majority of mass (~80%) coming from the \~15 most massive accretion events. The satellites that contribute to the stellar halo have median accretion times of ~9 Gyr in the past, while surviving satellite systems have median accretion times of ~5 Gyr in the past. This implies that stars associated with the inner halo should be quite different chemically from stars in surviving satellites and also from stars in the outer halo or those liberated in recent disruption events. We briefly discuss the expected spatial structure and phase space structure for halos formed in this manner. Searches for this type of structure offer a direct test of whether cosmology is indeed hierarchical on small scales.Comment: 22 pages, 16 figures, submitted to Ap

Mannose-binding lectin enhances Toll-like receptors 2 and 6 signaling from the phagosome

Innate immunity is the first-line defense against pathogens and relies on phagocytes, soluble components, and cell-surface and cytosolic pattern recognition receptors. Despite using hard-wired receptors and signaling pathways, the innate immune response demonstrates surprising specificity to different pathogens. We determined how combinatorial use of innate immune defense mechanisms defines the response. We describe a novel cooperation between a soluble component of the innate immune system, the mannose-binding lectin, and Toll-like receptor 2 that both specifies and amplifies the host response to Staphylococcus aureus. Furthermore, we demonstrate that this cooperation occurs within the phagosome, emphasizing the importance of engulfment in providing the appropriate cellular environment to facilitate the synergy between these defense pathways

N-terminal substitutions in HIV-1 gp41 reduce the expression of non-trimeric envelope glycoproteins on the virus

AbstractThe native, functional HIV-1 envelope glycoprotein (Env) complex is a trimer of two non-covalently associated subunits: the gp120 surface glycoprotein and the gp41 transmembrane glycoprotein. However, various non-functional forms of Env are present on virus particles and HIV-1-infected cells, some of which probably arise as the native complex decays. The aberrant forms include gp120–gp41 monomers and oligomers, as well as gp41 subunits from which gp120 has dissociated. The presence of non-functional Env creates binding sites for antibodies that do not recognize native Env complexes and that are, therefore, non-neutralizing. Non-native Env forms (monomers, dimers, tetramers and aggregates) can also arise when soluble gp140 proteins, lacking the cytoplasmic and transmembrane domains of gp41, are expressed for vaccine studies. We recently identified five amino acids in the gp41 N-terminal region (I535, Q543, S553, K567 and R588) that promote gp140 trimerization. We have now studied their influence on the function and antigenic properties of JR-FL Env expressed on the surfaces of pseudoviruses and Env-transfected cells. The 5 substitutions in gp41 reduce the expression of non-trimeric gp160s, without affecting trimer levels. Pseudovirions bearing the mutant Env are fully infectious with similar kinetics of Env-mediated fusion. Various non-neutralizing antibodies bind less strongly to the Env mutant, but neutralizing antibody binding is unaffected. Hence the gp41 substitutions do not adversely affect Env structure, supporting their use for making new Env-based vaccines. The mutant Env might also help in studies intended to correlate antibody binding to virus neutralization. Of note is that the 5 residues are much more frequent, individually or collectively, in viruses from subtypes other than B

Finding common ground: identifying and eilciting metacognition in ePortfolios

Research has suggested ePortfolios reveal and support students’ metacognition, that is, their awareness, tracking, and evaluation of their learning over time. However, due to the wide variety of purposes and audiences for ePortfolios, it has been unclear whether there might be common criteria for identifying and assessing metacognition in ePortfolios across varied contexts. The purpose of this study was to identify evidence of metacognition across ePortfolios of three distinct populations of students: traditional-age undergraduates, graduate Education students, and adults returning to school to complete a bachelor’s degree. We set out to explore if and how ePortfolios could support these different learners’ growth as reflective, intentional learners and professionals. Through a qualitative coding process, we identified four key metacognition markers across students’ ePortfolios in these three populations. We conclude students can be guided to engage in metacognition in ways through thoughtful assignment design and assessment process, no matter their context

Lambda-Cold Dark Matter, Stellar Feedback, and the Galactic Halo Abundance Pattern

(Abridged) The hierarchical formation scenario for the stellar halo requires the accretion and disruption of dwarf galaxies, yet low-metallicity halo stars are enriched in alpha-elements compared to similar, low-metallicity stars in dwarf spheroidal (dSph) galaxies. We address this primary challenge for the hierarchical formation scenario for the stellar halo by combining chemical evolution modelling with cosmologically-motivated mass accretion histories for the Milky Way dark halo and its satellites. We demonstrate that stellar halo and dwarf galaxy abundance patterns can be explained naturally within the LCDM framework. Our solution relies fundamentally on the LCDM model prediction that the majority of the stars in the stellar halo were formed within a few relatively massive, ~5 x 10^10 Msun, dwarf irregular (dIrr)-size dark matter halos, which were accreted and destroyed ~10 Gyr in the past. These systems necessarily have short-lived, rapid star formation histories, are enriched primarily by Type II supernovae, and host stars with enhanced [a/Fe] abundances. In contrast, dwarf spheroidal galaxies exist within low-mass dark matter hosts of ~10^9 Msun, where supernovae winds are important in setting the intermediate [a/Fe] ratios observed. Our model includes enrichment from Type Ia and Type II supernovae as well as stellar winds, and includes a physically-motivated supernovae feedback prescription calibrated to reproduce the local dwarf galaxy stellar mass - metallicity relation. We use representative examples of the type of dark matter halos we expect to host a destroyed ``stellar halo progenitor'' dwarf, a surviving dIrr, and a surviving dSph galaxy, and show that their derived abundance patterns, stellar masses, and gas masses are consistent with those observed for each type of system.Comment: 10 pages, 3 figures, version accepted by Ap

CD36 Mediates the Innate Host Response to β-Amyloid

Accumulation of inflammatory microglia in Alzheimer's senile plaques is a hallmark of the innate response to β-amyloid fibrils and can initiate and propagate neurodegeneration characteristic of Alzheimer's disease (AD). The molecular mechanism whereby fibrillar β-amyloid activates the inflammatory response has not been elucidated. CD36, a class B scavenger receptor, is expressed on microglia in normal and AD brains and binds to β-amyloid fibrils in vitro. We report here that microglia and macrophages, isolated from CD36 null mice, had marked reductions in fibrillar β-amyloid–induced secretion of cytokines, chemokines, and reactive oxygen species. Intraperitoneal and stereotaxic intracerebral injection of fibrillar β-amyloid in CD36 null mice induced significantly less macrophage and microglial recruitment into the peritoneum and brain, respectively, than in wild-type mice. Our data reveal that CD36, a major pattern recognition receptor, mediates microglial and macrophage response to β-amyloid, and imply that CD36 plays a key role in the proinflammatory events associated with AD

Response to Staphylococcus aureus requires CD36-mediated phagocytosis triggered by the COOH-terminal cytoplasmic domain

Phagocyte recognition and clearance of bacteria play essential roles in the host response to infection. In an on-going forward genetic screen, we identify the Drosophila melanogaster scavenger receptor Croquemort as a receptor for Staphylococcus aureus, implicating for the first time the CD36 family as phagocytic receptors for bacteria. In transfection assays, the mammalian Croquemort paralogue CD36 confers binding and internalization of Gram-positive and, to a lesser extent, Gram-negative bacteria. By mutational analysis, we show that internalization of S. aureus and its component lipoteichoic acid requires the COOH-terminal cytoplasmic portion of CD36, specifically Y463 and C464, which activates Toll-like receptor (TLR) 2/6 signaling. Macrophages lacking CD36 demonstrate reduced internalization of S. aureus and its component lipoteichoic acid, accompanied by a marked defect in tumor necrosis factor-α and IL-12 production. As a result, Cd36−/− mice fail to efficiently clear S. aureus in vivo resulting in profound bacteraemia. Thus, response to S. aureus requires CD36-mediated phagocytosis triggered by the COOH-terminal cytoplasmic domain, which initiates TLR2/6 signaling

High sensitivity of summer temperatures to stratospheric sulfur loading from volcanoes in the Northern Hemisphere

This work was funded by an ERC (European Research Council) Marie Curie Career Integration Grant (CIG14-631752) and a Philip Leverhulme prize in Earth Sciences (PLP-2021-167) from the Leverhulme Trust awarded to A.B. WH is funded by a UKRI Future Leaders Fellowship (MR/S033505/1). M.S. acknowledges the support of the ERC under the European Union’s Horizon 2020 research and innovation programme (grant agreement 820047). H.M.I. and L.C. were both funded by IAPETUS and IAPETUS2 NERC Doctoral Training Partnership. The Tunu2013 and NEEM_2011_S1 ice cores were collected and analyzed for sulfur and other chemical species used to establish the ice core chronologies with funding from NSF grants 1204176 and 0909541 to J.R.M., respectively, and ice cores were sampled with funding from NSF grant 1340174.The 540s, 1450s, and 1600s represent three of the five coldest decades in the Common Era (CE). In each of these cases, the cause of these cold pulses has been attributed to large volcanic eruptions. However, the provenance of the eruption and magnitude of the volcanic forcing remains uncertain. Here, we use high-resolution sulfur isotopes in Greenland and Antarctic ice cores measured across these events to provide a means of improving sulfur loading estimates for these eruptions. In each case, the largest reconstructed tree-ring cooling is associated with an extratropical eruption, and the high-altitude stratospheric sulfate loading of these events is substantially smaller than previous estimates (by up to a factor of two). These results suggest an increased sensitivity of the reconstructed Northern Hemisphere summer temperature response to extratropical eruptions. This highlights the importance of climate feedbacks and processes that amplify and prolong the cooling signal from high latitudes, such as changes in sea ice extent and ocean heat content.Publisher PDFPeer reviewe

Drosophila MUS312 and the Vertebrate Ortholog BTBD12 Interact with DNA Structure-Specific Endonucleases in DNA Repair and Recombination

DNA recombination and repair pathways require structure-specific endonucleases to process DNA structures that include forks, flaps, and Holliday junctions. Previously, we determined that the Drosophila MEI-9-ERCC1 endonuclease interacts with the novel MUS312 protein to produce meiotic crossovers, and that MUS312 has a MEI-9-independent role in interstrand crosslink (ICL) repair. The importance of MUS312 to pathways crucial for maintaining genomic stability in Drosophila prompted us to search for orthologs in other organisms. Based on sequence, expression pattern, conserved protein-protein interactions, and ICL repair function, we determined that the mammalian ortholog of MUS312 is BTBD12. Orthology between these proteins and S. cerevisiae Slx4 helped identify a conserved interaction with a second structure-specific endonuclease, SLX1. Genetic and biochemical evidence described here and in related papers suggest that MUS312 and BTBD12 direct Holliday junction resolution by at least two distinct endonucleases in different recombination and repair contexts