The architecture of the extracellular matrix (ECM) directs cell behavior by providing spatial and mechanical cues to which cells respond. In addition to soluble chemical factors, physical interactions between the cell and ECM regulate primary cell processes, including differentiation, migration, and proliferation. Advances in microtechnology and, more recently, nanotechnology provide a powerful means to study the influence of the ECM on cell behavior. By recapitulating local architectures that cells encounter in vivo, we can elucidate and dissect the fundamental signal transduction pathways that control cell behavior in critical developmental, physiological, and pathological processes.

We describe the first results from the Outer Limits Survey, an NOAO survey designed to detect, map, and characterize the extended structure of the Large and Small Magellanic Clouds. The survey consists of deep images of 55 0.6 o ×0.6 o fields distributed at distances up to 20 o from the Clouds, with 10 fields at larger distances representing controls for contamination by Galactic foreground stars and background galaxies. The field locations probe the outer structure of both the LMC and SMC, as well as explore areas defined by the Magellanic Stream, the Leading Arm, and the LMC orbit as recently measured from its proper motion. The images were taken with C, M, R, I, and DDO51 filters on the CTIO Blanco 4m telescope and Mosaic2 camera, with supporting calibration observations taken at the CTIO 0.9-m telescope. The CRI images reach depths below the oldest main sequence turnoffs at the distance of the Clouds, thus yielding numerous probes of structure combined with good ability to measure stellar ages and metallicities. The M and DDO51 images allow for discrimination of LMC and SMC giant stars from foreground dwarfs, allowing us to use giants as additional probes of Cloud structure and populations.From photometry of 8 fields located at radii of 7 o to 19 o north of the LMC bar, we find main sequence stars associated with the LMC out to 16 o from the LMC center, while the much rarer giants can only be convincingly detected out to 11 o . In one field, designated as a control, we see the unmistakable signature of the Milky Way globular cluster NGC 1851, which lies several tidal radii away from the field center. The color-magnitude diagrams show that while at 7 o radius LMC populations as young as 500 Myr are present, at radii 11 o only the LMC's underlying old metal-poor ([M/H]∼ −1) population remains, demonstrating the existence of a mean population gradient at these radii. Nevertheless, even at extreme large distances, the dominant age is significantly younger than that of the Galactic globular clusters. The main-sequence star counts follow an exponential decline with distance with a scale length of 1.15 kpc, essentially the same scale length as gleaned for the inner LMC disk from prior studies. While we cannot rule out the existence of undetected tidal features elsewhere in the LMC periphery, the detection of an ordered structure to 12 disk scale lengths is unprecedented, and adds to the puzzle of the LMC's interaction history with the SMC and the Milky Way. Our results do not rule out the possible existence of an LMC stellar halo, which we show may only begin to dominate over the disk at still larger radii than where we have detected LMC populations.

We present the star cluster catalogues for 17 dwarf and irregular galaxies in the HST Treasury Program 'Legacy ExtraGalactic UV Survey' (LEGUS). Cluster identification and photometry in this sub-sample are similar to that of the entire LEGUS sample, but special methods were developed to provide robust catalogues with accurate fluxes due to low cluster statistics. The colours and ages are largely consistent for two widely used aperture corrections, but a significant fraction of the clusters are more compact than the average training cluster. However, the ensemble luminosity, mass, and age distributions are consistent suggesting that the systematics between the two methods are less than the random errors. When compared with the clusters from previous dwarf galaxy samples, we find that the LEGUS catalogues are more complete and provide more accurate total fluxes. Combining all clusters into a composite dwarf galaxy, we find that the luminosity and mass functions can be described by a power law with the canonical index of −2 independent of age and global SFR binning. The age distribution declines as a power law, with an index of ≈− 0.80 ± 0.15, independent of cluster mass and global SFR binning. This decline of clusters is dominated by cluster disruption since the combined star formation histories and integrated-light SFRs are both approximately constant over the last few hundred Myr. Finally, we find little evidence for an upper-mass cut-off (<2σ ) in the composite cluster mass function, and can rule out a truncation mass below ≈10 4.5 M but cannot rule out the existence of a truncation at higher masses.

We measure the weak-lensing masses and galaxy distributions of four massive galaxy clusters observed during the Science Verification phase of the Dark Energy Survey. This pathfinder study is meant to 1) validate the DECam imager for the task of measuring weak-lensing shapes, and 2) utilize DECam's large field of view to map out the clusters and their environments over 90 arcmin. We conduct a series of rigorous tests on astrometry, photometry, image quality, PSF modeling, and shear measurement accuracy to single out flaws in the data and also to identify the optimal data processing steps and parameters. We find Science Verification data from DECam to be suitable for the lensing analysis described in this paper. The PSF is generally well-behaved, but the modeling is rendered difficult by a flux-dependent PSF width and ellipticity. We employ photometric redshifts to distinguish between foreground and background galaxies, and a red-sequence cluster finder to provide cluster richness estimates and cluster-galaxy distributions. By fitting NFW profiles to the clusters in this study, we determine weak-lensing masses that are in agreement with previous work. For Abell 3261, we provide the first estimates of redshift, weak-lensing mass, and richness. In addition, the cluster-galaxy distributions indicate the presence of filamentary structures attached to 1E 0657-56 and RXC J2248.7-4431, stretching out as far as 1 degree (approximately 20 Mpc), showcasing the potential of DECam and DES for detailed studies of degree-scale features on the sky.

SUMMARY Glioblastoma multiforme is a heterogeneous and infiltrative cancer with dismal prognosis. Studying the migratory behavior of tumor-derived cell populations can be informative but places a high premium on the precision of in vitro methods and their relevance of in vivo conditions. In particular, the analysis of 2D cell migration may not reflect invasion into 3D extracellular matrices in vivo. Here we describe a method that allows time-resolved studies of primary cell migration with single-cell resolution on a fibrillar surface that closely mimics in vivo 3D migration. We used this platform to screen 14 patient-derived glioblastoma samples. We observed that the migratory phenotype of a subset of cells in response to Platelet-derived growth factor was highly predictive of tumor location and recurrence in the clinic. Therefore, migratory phenotypic classifiers analyzed at the single-cell level in a patient-specific way can provide high diagnostic and prognostic value for invasive cancers.

Hα observations centred on galaxies selected from the Hi Parkes All Sky Survey (HiPASS, Barnes et al. 2001) typically show one and sometimes two star-forming galaxies within the ∼15' beam of the Parkes 64-m Hi detections. In our Survey of Ionization in Neutral Gas Galaxies (SINGG, Meurer et al. 2006) we found fifteen cases of HiPASS sources containing four or more emission line galaxies (ELGs). We name these fields Choir groups. In the most extreme case we found a field with at least nine ELGs. In this paper we present a catalogue of Choir group members in the context of the wider SINGG sample.The dwarf galaxies in the Choir groups would not be individually detectable in HiPASS at the observed distances if they were isolated, but are detected in SINGG narrow-band imaging due to their membership of groups with sufficiently large total Hi mass. The ELGs in these groups are similar to the wider SINGG sample in terms of size, Hα equivalent width, and surface brightness.Eight of these groups have two large spiral galaxies with several dwarf galaxies and may be thought of as morphological analogues of the Local Group. However, on average our groups are not significantly Hi-deficient, suggesting that they are at an early stage of assembly, and more like the M81 group. The Choir groups are very compact at typically only 190 kpc in projected distance between the two brightest members. They are very similar to SINGG fields in terms of star formation efficiency (the ratio of star formation rate to Hi mass; SFE), showing an increasing trend in SFE with stellar mass.

Noonan syndrome is a multiorgan system disorder mediated by genetic defects along the RASknown as RASopathies. It is the second most common syndromic cause of congenital heart disease and, in ∼20% of the cases, is associated with severe lymphatic disorders, including chylothorax and protein-losing enteropathy. Recently, we reported on the use of mitogen-activated protein kinase inhibition in a patient with an ARAF mutation and severe lymphatic disorder leading to an abrupt improvement in symptoms and complete remodeling of the central lymphatic system. Here, we present a patient with Noonan syndrome and severe lymphatic abnormality, leading to transfusion-dependent upper gastrointestinal bleeding and protein-losing enteropathy. The patient stopped responding to medical therapy and underwent several lymphatic interventional procedures, which led only to a temporary improvement in symptoms. Because of a lack of other treatment options, an expanded access approval was obtained, and the patient initiated treatment by mitogen-activated protein kinase inhibition using trametinib. This led to resolution of her symptoms, with complete normalization of her electrolyte levels, hemoglobin, and albumin within 3 months of starting the drug. Similar to the previously reported case, she also had complete and generalized remodeling of her lymphatic system. In patients with RAS pathway defects complicated by a severe lymphatic disorder, inhibition of the RAS-MAPK pathway should be considered as a possible treatment option in patients who failed conventional treatment and might be a first-line treatment in the future.

Glioblastoma (GBM) remains the most aggressive primary brain cancer in adults. Similar to other cancers, GBM cells undergo metabolic reprogramming to promote proliferation and survival. Glycolytic inhibition is widely used to target such reprogramming. However, the stability of glycolytic inhibition in GBM remains unclear especially in a hypoxic tumor microenvironment. In this study, it was determined that glucose-6-phosphatase-α (G6PC/G6Pase) expression is elevated in GBM when compared to normal brain. Human-derived brain tumor initiating cells (BTICs) utilize this enzyme to counteract glycolytic inhibition induced by 2-Deoxy-D-glucose (2DG) and sustain malignant progression. Down-regulation of G6PC renders the majority of these cells unable to survive glycolytic inhibition, and promotes glycogen accumulation through the activation of glycogen synthase (GYS1) and inhibition of glycogen phosphorylase (PYGL). Moreover, BTICs that survive G6PC knockdown are less aggressive (reduced migration, invasion, proliferation, and increased astrocytic differentiation). Collectively, these findings establish G6PC as a key enzyme with pro-malignant functional consequences that has not been previously reported in GBM and identify it as a potential therapeutic target.