Mass and Light in the Universe

We present a weak lensing and photometric study of six half by half degree fields observed at the CFHT using the UH8K CCD mosaic camera. The fields were observed for a total of 2 hours each in I and V, resulting in catalogs containing ~ 20 000 galaxies per passband per field. We use V-I color and I magnitude to select bright early type galaxies at redshifts 0.1 < z < 0.9. We measure the gravitational shear from faint galaxies in the range 21 < m_I < 25 from a composite catalog and find a strong correlation with that predicted from the early types if they trace the mass with mass-to-light ratio 300\pm75 h (in solar units) for a flat (Omega_m0 = 0.3, Omega_l0 = 0.7) lambda cosmology and 400\pm100 h for Einstein-de Sitter. We make two-dimensional reconstructions of the mass surface density. Cross-correlation of the measured mass surface density with that predicted from the early type galaxy distribution shows a strong peak at zero lag (significant at the 5.2-sigma level). We azimuthally average the cross- and auto-correlation functions. We conclude that the profiles are consistent with early type galaxies tracing mass on scales of > 45 arcsec (> 200 kpc at z = 0.5). We sub-divide our bright early type galaxies by redshift and obtain similar conclusions. These mass-to-light ratios imply \Omega_m0 = 0.10\pm0.02 (\Omega_m0 = 0.13\pm0.03 for Einstein-de Sitter) of closure density.Comment: 27 pages, 19 figs (4 ps, 15 gif), 4 tables, accepted for publication in Ap.J. (email Gillian for better resolution ps versions of gif greyscale plots

Elevated ACKR2 expression is a common feature of inflammatory arthropathies

Objectives. Chemokines are essential contributors to leucocyte accumulation at sites of inflammatory pathology. Interfering with chemokine or chemokine receptor function therefore represents a plausible therapeutic option. However, our currently limited understanding of chemokine orchestration of inflammatory responses means that such therapies have not yet been fully developed. We have a particular interest in the family of atypical chemokine receptors that fine-tune, or resolve, chemokine-driven responses. In particular we are interested in atypical chemokine receptor 2 (ACKR2), which is a scavenging receptor for inflammatory CC-chemokines and that therefore helps to resolve in vivo inflammatory responses. The objective of the current study was to examine ACKR2 expression in common arthropathies. Methods. ACKR2 expression was measured by a combination of qPCR and immuno-histochemistry. In addition, circulating cytokine and chemokine levels in patient plasma were assessed using multiplexing approaches. Results. Expression of ACKR2 was elevated on peripheral blood cells as well as on leucocytes and stromal cells in synovial tissue. Expression on peripheral blood leucocytes correlated with, and could be regulated by, circulating cytokines with particularly strong associations being seen with IL-6 and hepatocyte growth factor. In addition, expression within the synovium was coincident with aggregates of lymphocytes, potentially atopic follicles and sites of high inflammatory chemokine expression. Similarly increased levels of ACKR2 have been reported in psoriasis and SSc. Conclusion. Our data clearly show increased ACKR2 in a variety of arthropathies and taking into account our, and others’, previous data we now propose that elevated ACKR2 expression is a common feature of inflammatory pathologies

Galaxy Halo Masses from Galaxy-Galaxy Lensing

We present measurements of the extended dark halo profiles of bright early type galaxies at redshifts 0.1 to 0.9 obtained via galaxy-galaxy lensing analysis of images taken at the CFHT using the UH8K CCD mosaic camera. Six half degree fields were observed for a total of 2 hours each in I and V, resulting in catalogs containing ~20 000 galaxies per field. We used V-I color and I magnitude to select bright early type galaxies as the lens galaxies, yielding a sample of massive lenses with fairly well determined redshifts and absolute magnitudes M ~ M_* \pm 1. We paired these with faint galaxies lying at angular distances 20" to 60", corresponding to physical radii of 26 to 77 kpc (z = 0.1) and 105 to 315 kpc (z = 0.9), and computed the mean tangential shear of the faint galaxies. The shear falls off with radius roughly as expected for flat rotation curve halos. The shear values were weighted in proportion to the square root of the luminosity of the lens galaxy. Our results give a value for the average mean rotation velocity of an L_* galaxy halo at r~50-200 kpc of v_* = 238^{+27}_{-30} km per sec for a flat lambda (Omega_m0 = 0.3, Omega_l0 = 0.7) cosmology (v_* = 269^{+34}_{-39} km per sec for Einstein-de Sitter), and with little evidence for evolution with redshift. We compare to halo masses measured by other groups/techniques. We find a mass-to-light ratio of ~121\pm28h(r/100 kpc) and these halos constitute Omega ~0.04 \pm 0.01(r/100 kpc) of closure density. (abridged)Comment: Accepted for publication in ApJ (minor modifications) - 32 pages, 11 figs, 5 table

Divergent evolution of protein conformational dynamics in dihydrofolate reductase.

Molecular evolution is driven by mutations, which may affect the fitness of an organism and are then subject to natural selection or genetic drift. Analysis of primary protein sequences and tertiary structures has yielded valuable insights into the evolution of protein function, but little is known about the evolution of functional mechanisms, protein dynamics and conformational plasticity essential for activity. We characterized the atomic-level motions across divergent members of the dihydrofolate reductase (DHFR) family. Despite structural similarity, Escherichia coli and human DHFRs use different dynamic mechanisms to perform the same function, and human DHFR cannot complement DHFR-deficient E. coli cells. Identification of the primary-sequence determinants of flexibility in DHFRs from several species allowed us to propose a likely scenario for the evolution of functionally important DHFR dynamics following a pattern of divergent evolution that is tuned by cellular environment

Atypical chemokine receptor ACKR2 controls branching morphogenesis in the developing mammary gland

Macrophages are important regulators of branching morphogenesis during development and postnatally in the mammary gland. Regulation of macrophage dynamics during these processes can therefore have a profound impact on development. We demonstrate here that the developing mammary gland expresses high levels of inflammatory CC-chemokines, which are essential in vivo regulators of macrophage migration. We further demonstrate that the atypical chemokine receptor ACKR2, which scavenges inflammatory CC-chemokines, is differentially expressed during mammary gland development. We have previously shown that ACKR2 regulates macrophage dynamics during lymphatic vessel development. Here, we extend these observations to reveal a novel role for ACKR2 in regulating the postnatal development of the mammary gland. Specifically, we show that Ackr2−/− mice display precocious mammary gland development. This is associated with increased macrophage recruitment to the developing gland and increased density of the ductal epithelial network. These data demonstrate that ACKR2 is an important regulator of branching morphogenesis in diverse biological contexts and provide the first evidence of a role for chemokines and their receptors in postnatal development processes

Elucidating the crystal-chemistry of Jbel Rhassoul stevensite (Morocco) by advanced analytical techniques

The composition of Rhassoul clay is controversial regarding the nature of the puremineral clay fraction which is claimed to be stevensite rather than saponite. In this study, the raw and mineral fractions were characterized using various techniques including Fourier transform infrared spectroscopy and magic angle spinning nuclear magnetic resonance (MAS NMR). The isolated fine clay mineral fraction contained a larger amount of Al (>1 wt.%) than that reported for other stevensite occurrences. The 27Al MAS NMR technique confirmed that the mineral is stevensite in which the Al is equally split between the tetrahedral and octahedral coordination sites. The 29Si NMR spectrum showed a single unresolved resonance indicating little or no short-range ordering of silicon. The chemical composition of the stevensite from Jbel Rhassoul was determined to be ((Na0.25K0.20 (Mg5.04Al0.37Fe0.20&0.21)5.61(Si7.76Al0.24)8O20(OH)4). This formula differs from previous compositions described from this locality and shows it to be an Al-bearing lacustrine clay mineral

Myc Cooperates with Ras by Programming Inflammation and Immune Suppression.

The two oncogenes KRas and Myc cooperate to drive tumorigenesis, but the mechanism underlying this remains unclear. In a mouse lung model of KRasG12D-driven adenomas, we find that co-activation of Myc drives the immediate transition to highly proliferative and invasive adenocarcinomas marked by highly inflammatory, angiogenic, and immune-suppressed stroma. We identify epithelial-derived signaling molecules CCL9 and IL-23 as the principal instructing signals for stromal reprogramming. CCL9 mediates recruitment of macrophages, angiogenesis, and PD-L1-dependent expulsion of T and B cells. IL-23 orchestrates exclusion of adaptive T and B cells and innate immune NK cells. Co-blockade of both CCL9 and IL-23 abrogates Myc-induced tumor progression. Subsequent deactivation of Myc in established adenocarcinomas triggers immediate reversal of all stromal changes and tumor regression, which are independent of CD4+CD8+ T cells but substantially dependent on returning NK cells. We show that Myc extensively programs an immune suppressive stroma that is obligatory for tumor progression

Proteomic analysis of the processes leading to Madurella mycetomatis grain formation in Galleria mellonella larvae

Mycetoma is a neglected chronic and granulomatous infection primarily associated with the fungal pathogen Madurella mycetomatis. Characteristic of this infection is the formation of grains. However, the processes leading to grain formation are not known. In this study, we employed a proteomic approach to characterise M. mycetomatis grain formation in Galleria mellonella larvae and map the processes leading to grain formation over time. For this, at 1 day, 3 days and 7 days post-inoculation, proteins from grains and hemolymph were extracted and analysed by label-free mass spectrometry. A total of 87, 51 and 48 M. mycetomatis proteins and 713, 997, 18 G. mellonella proteins were found in grains on day 1, 3 and 7 post-inoculation respectively. M. mycetomatis proteins were mainly involved in cellular metabolic processes and numerous enzymes were encountered. G. mellonella proteins were primarily involved in the nodulation process. The proteins identified were linked to nodulation and grain formation and four steps of grain formation were identified. The results of this proteomic approach could in the future be used to design novel strategies to interfere with mycetoma grain formation and to combat this difficult to treat infection