The low mass population of the Vela OB2 association from Gaia

The first Gaia Data Release presents an opportunity to characterise the low-mass population of OB associations, providing larger statistical samples and better constraints on the formation and evolution of clusters and associations. Using previously known low mass members in a small region of Vela OB2 we have designed selection criteria that combine Gaia and 2MASS photometry, independently of any astrometric information, to identify low-mass pre-main-sequence (PMS) stars over the wider association area. Our method picks out the known clusters of young stars around Velorum and NGC-2547, but also identifies other over-densities that may represent previously unknown clusters. There are clear differences in the spatial distributions of the low-mass and the high-mass OB populations, suggesting either that the structure and dynamics of these populations has evolved separately or that the initial mass function can vary considerably on small scales within a single association

A kinematically hot population of young stars in the solar neighbourhood

In the last three decades several hundred nearby members of young stellar moving groups (MGs) have been identified, but there has been less systematic effort to quantify or characterise young stars that do not belong to previously identified MGs. Using a kinematically unbiased sample of 225 lithium-rich stars within 100 pc, we find that only $50 \pm 10$ per cent of young ($\lesssim 125$ Myr), low-mass ($0.5<M/M_{\odot}<1.0$) stars, are kinematically associated with known MGs. Whilst we find some evidence that six of the non-MG stars may be connected with the Lower Centaurus-Crux association, the rest form a kinematically "hotter" population, much more broadly dispersed in velocity, and with no obvious concentrations in space. The mass distributions of the MG members and non-MG stars is similar, but the non-MG stars may be older on average. We briefly discuss several explanations for the origin of the non-MG population

Mesangial cells are key contributors to the fibrotic damage seen in the lupus nephritis glomerulus.

Background: Lupus nephritis (LN) affects up to 80% of juvenile-onset systemic lupus erythematosus patients. Mesangial cells (MCs) comprise a third of the glomerular cells and are key contributors to fibrotic changes within the kidney. This project aims to identify the roles of MCs in an in vitro model of LN. Methods: Conditionally immortalised MCs were treated with pro-inflammatory cytokines or with patient sera in an in vitro model of LN and assessed for their roles in inflammation and fibrosis. Results: MCs were shown to produce pro-inflammatory cytokines in response to a model of the inflammatory environment in LN. Further the cells expressed increased levels of mRNA for extracellular matrix (ECM) proteins (COL1A1, COL1A2, COL4A1 and LAMB1), matrix metalloproteinase enzymes (MMP9) and tissue inhibitors of matrix metalloproteinases (TIMP1). Treatment of MCs with serum from patients with active LN was able to induce a similar, albeit milder phenotype. Treatment of MCs with cytokines or patient sera was able to induce secretion of TGF-β1, a known inducer of fibrotic changes. Inhibition of TGF-β1 actions through SB-431542 (an activin A receptor type II-like kinase (ALK5) inhibitor) was able to reduce these responses suggesting that the release of TGF-β1 plays a role in these changes. Conclusions: MCs contribute to the inflammatory environment in LN by producing cytokines involved in leukocyte recruitment, activation and maturation. Further the cells remodel the ECM via protein deposition and enzymatic degradation. This occurs through the actions of TGF-β1 on its receptor, ALK5. This may represent a potential therapeutic target for treatment of LN-associated fibrosis

The dynamics of the γ Vel cluster and nearby Vela OB2 association

The kinematics of low-mass stars in nearby OB associations can provide clues about their origins and evolution. Combining the precise positions, proper motions, and parallaxes given in the second Gaia Data Release with radial-velocity measurements obtained with the Hermes spectrograph at the Anglo-Australian Telescope, we have an opportunity to study in detail the kinematics of low-mass stars belonging to the nearby γ Vel cluster and the Vela OB2 association it is projected against. The presence of lithium is used to confirm the youth of our targets. We separate our sample into the cluster and association populations based on the Gaia-ESO Survey membership probabilities their parallaxes, and kinematics. We find strong evidence for expansion in the OB association population with at least 4σ significance along all three axes, though the expansion is notably anisotropic. We discuss these results in the context of cluster and association dispersal theories

Galectin-3-null mice display defective neutrophil clearance during acute inflammation

Galectin-3 has been associated with a plethora of proinflammatory functions because of its ability, among others, to promote neutrophil activation and because of the reduction in neutrophil recruitment in models of infection in Gal-3-null mice. Conversely, it has also been linked to resolution of inflammation through its actions as an opsonin and its ability to promote efferocytosis of apoptotic neutrophils. Using a self-resolving model of peritonitis, we have addressed the modulation and role of Gal-3 in acute inflammation. We have shown that Gal-3 expression is increased in neutrophils that travel to the inflamed peritoneum and that cellular localization of this lectin is modulated during the course of the inflammatory response. Furthermore, neutrophil recruitment to the inflamed peritoneum is increased in Gal-3–null mice during the course of the response, and that correlates with reduced numbers of monocytes/macrophages in the cavities of those mice, as well as reduced apoptosis and efferocytosis of Gal-3–null neutrophils. These data indicate a role for endogenous Gal-3 in neutrophil clearance during acute inflammation

The human glomerular endothelial cells are potent pro-inflammatory contributors in an in vitro model of lupus nephritis

Juvenile-onset lupus nephritis (LN) affects up to 80% of juvenile-onset systemic lupus erythematosus patients (JSLE). As the exact role of human renal glomerular endothelial cells (GEnCs) in LN has not been fully elucidated, the aim of this study was to investigate their involvement in LN. Conditionally immortalised human GEnCs (ciGEnCs) were treated with pro-inflammatory cytokines known to be involved in LN pathogenesis and also with LPS. Secretion and surface expression of pro-inflammatory proteins was quantified via ELISA and flow cytometry. NF-κΒ and STAT-1 activation was investigated via immunofluorescence. Serum samples from JSLE patients and from healthy controls were used to treat ciGEnCs to determine via qRT-PCR potential changes in the mRNA levels of pro-inflammatory genes. Our results identified TNF-α, IL-1β, IL-13, IFN-γ and LPS as robust in vitro stimuli of ciGEnCs. Each of them led to significantly increased production of different pro-inflammatory proteins, including; IL-6, IL-10, MCP-1, sVCAM-1, MIP-1α, IP-10, GM-CSF, M-CSF, TNF-α, IFN-γ, VCAM-1, ICAM-1, PD-L1 and ICOS-L. TNF-α and IL-1β were shown to activate NF-κB, whilst IFN-γ activated STAT-1. JSLE patient serum promoted IL-6 and IL-1β mRNA expression. In conclusion, our in vitro model provides evidence that human GEnCs play a pivotal role in LN-associated inflammatory process

The structure and 3D kinematics of vela OB2

The kinematics of stars in OB associations can provide insights into their formation, dynamical evolution, and eventual fate. The low-mass stellar content of OB associations are sufficiently numerous as to provide a detailed sampling of their kinematic properties, however spectroscopy is required to confirm the youth of individual stars and to get 3D kinematics. In this paper, we present and analyse results from a large spectroscopic survey of Vela OB2 conducted using 2dF/HERMES on the AAT. This spectroscopy is used to confirm the youth of candidate young stars and determine radial velocities, which are combined with proper motions and parallaxes from Gaia to measure 3D positions and velocities. We identify multiple separate kinematic groups in the region, for which we measure velocity dispersions and infer their virial states. We measure expansion rates for all these groups and find strong evidence for anisotropic expansion in the Vela OB2 association of at least 11σ significance in all three dimensions, as well as some evidence for expansion in the γ Vel and P Puppis clusters. We trace back the motions of these groups into the past and find that the open cluster NGC 2547 is an interloper in the Vela OB2 region and actually formed >100 pc away from the association. We conclude that Vela OB2 must have formed with considerable spatial and kinematic substructure over a time-scale of ∼10 Myr, with clear temporal substructure within the association, but no clear evidence for an age gradient

Solar-type dynamo behaviour in fully convective stars without a tachocline

In solar-type stars (with radiative cores and convective envelopes), the magnetic field powers star spots, flares and other solar phenomena, as well as chromospheric and coronal emission at ultraviolet to X-ray wavelengths. The dynamo responsible for generating the field depends on the shearing of internal magnetic fields by differential rotation. The shearing has long been thought to take place in a boundary layer known as the tachocline between the radiative core and the convective envelope. Fully convective stars do not have a tachocline and their dynamo mechanism is expected to be very different, although its exact form and physical dependencies are not known. Here we report observations of four fully convective stars whose X-ray emission correlates with their rotation periods in the same way as in Sun-like stars. As the X-ray activity - rotation relationship is a well-established proxy for the behaviour of the magnetic dynamo, these results imply that fully convective stars also operate a solar-type dynamo. The lack of a tachocline in fully convective stars therefore suggests that this is not a critical ingredient in the solar dynamo and supports models in which the dynamo originates throughout the convection zone.Comment: 6 pages, 1 figure. Accepted for publication in Nature (28 July 2016). Author's version, including Method

Solubility evaluation of murine hybridoma antibodies

The successful development of antibody therapeutics depends on the molecules having properties that are suitable for manufacturing, as well as use by patients. Because high solubility is a desirable property for antibodies, screening for solubility has become an essential step during the early candidate selection process. In considering the screening process, we formed a hypothesis that hybridoma antibodies are filtered by nature to possess high solubility and tested this hypothesis using a large number of murine hybridoma-derived antibodies. Using the cross-interaction chromatography (CIC) method, we screened the solubility of 92 murine hybridoma-derived monoclonal antibodies and found that all of these molecules exhibited CIC profiles that are indicative of high solubility (>100mg/mL). Further investigations revealed that variable region N-linked glycosylation or isoelectric parameters are unlikely to contribute to the high solubility of these antibodies. These results support the general hypothesis that hybridoma monoclonal antibodies are highly soluble