Long-term in vitro 3D hydrogel co-culture model of inflammatory bowel disease

The in vitro study of the pathogenesis of inflammatory bowel disease (IBD) requires a cell model which closely reflects the characteristics of the in vivo intestinal epithelium. This study aimed to investigate the application of L-pNIPAM hydrogel as a scaffold to develop a long-term 3D co-culture model of Caco-2 and HT29-MTX cells under conditions analogous to inflammation, to determine its potential use in studying IBD. Monocultures and co-cultures were layered on L-pNIPAM hydrogel scaffolds and maintained under dynamic culture conditions for up to 12 weeks. Treatments with IL-1β, TNFα, and hypoxia for 1 week were used to create an inflammatory environment. Following prolonged culture, the metabolic activity of Caco-2 monoculture and 90% Caco-2/10% HT29-MTX co-cultures on L-pNIPAM hydrogels were increased, and finger-like structures, similar in appearance to villi were observed. Following treatment with IL-1β, TNFα and hypoxia, ALP and ZO-1 were decreased, MUC2 increased, and MUC5AC remained unchanged. ADAMTS1 was increased in response to hypoxia. Caspase 3 expression was increased in response to TNFα and hypoxic conditions. In conclusion, L-pNIPAM hydrogel supported long-term co-culture within a 3D model. Furthermore, stimulation with factors seen during inflammation recapitulated features seen during IBD

Governors tend to appoint Senators who most resemble voters in the state, rather than ideologues.

For over a century, state governors have had the power to appoint US Senators to vacant seats, a power which runs against the idea of Senators as being democratic representatives. But do governors appoint those with similar ideologies to themselves? In new research which reviewed senate candidates considered by governors to fill vacancies, Christopher Cooper, H. Gibbs Knotts, and Jordan Ragusa find that while they rarely appoint senators from a different party, they tend to skew towards the middle – appointing those who are closest to the ideology of the state’s median voter

Neurocardiovascular deficits in the Q175 mouse model of Huntington's disease.

Cardiovascular dysautonomia as well as the deterioration of circadian rhythms are among the earliest detectable pathophysiological changes in individuals with Huntington's disease (HD). Preclinical research requires mouse models that recapitulate disease symptoms and the Q175 knock-in model offers a number of advantages but potential autonomic dysfunction has not been explored. In this study, we sought to test the dual hypotheses that cardiovascular dysautonomia can be detected early in disease progression in the Q175 model and that this dysfunction varies with the daily cycle. Using radiotelemetry implants, we observed a significant reduction in the diurnal and circadian activity rhythms in the Q175 mutants at the youngest ages. By middle age, the autonomically driven rhythms in core body temperature were highly compromised, and the Q175 mutants exhibited striking episodes of hypothermia that increased in frequency with mutant huntingtin gene dosage. In addition, Q175 mutants showed higher resting heart rate (HR) during sleep and greatly reduced correlation between activity and HR HR variability was reduced in the mutants in both time and frequency domains, providing more evidence of autonomic dysfunction. Measurement of the baroreceptor reflex revealed that the Q175 mutant could not appropriately increase HR in response to a pharmacologically induced decrease in blood pressure. Echocardiograms showed reduced ventricular mass and ejection fraction in mutant hearts. Finally, cardiac histopathology revealed localized points of fibrosis resembling those caused by myocardial infarction. Thus, the Q175 mouse model of HD exhibits cardiovascular dysautonomia similar to that seen in HD patients with prominent sympathetic dysfunction during the resting phase of the activity rhythm

Neurons derived from human embryonic stem cells extend long-distance axonal projections through growth along host white matter tracts after intra-cerebral transplantation

Human pluripotent stem cells have the capacity for directed differentiation into a wide variety of neuronal subtypes that may be useful for brain repair. While a substantial body of research has lead to a detailed understanding of the ability of neurons in fetal tissue grafts to structurally and functionally integrate after intra-cerebral transplantation, we are only just beginning to understand the in vivo properties of neurons derived from human pluripotent stem cells. Here we have utilized the human embryonic stem (ES) cell line Envy, which constitutively expresses green fluorescent protein (GFP), in order to study the in vivo properties of neurons derived from human ES cells. Rapid and efficient neural induction, followed by differentiation as neurospheres resulted in a GFP+ neural precursor population with traits of neuroepithelial and dorsal forebrain identity. Ten weeks after transplantation into neonatal rats, GFP+ fiber patterns revealed extensive axonal growth in the host brain, particularly along host white matter tracts, although innervation of adjacent nuclei was limited. The grafts were composed of a mix of neural cell types including differentiated neurons and glia, but also dividing neural progenitors and migrating neuroblasts, indicating an incomplete state of maturation at 10 weeks. This was reflected in patch-clamp recordings showing stereotypical properties appropriate for mature functional neurons, including the ability to generate action potentials, as well profiles consistent for more immature neurons. These findings illustrate the intrinsic capacity for neurons derived from human ES cells to integrate at a structural and functional level following transplantation

Comparison of work fluctuation relations

We compare two predictions regarding the microscopic fluctuations of a system that is driven away from equilibrium: one due to Crooks [J. Stat. Phys. 90, 1481 (1998)] which has gained recent attention in the context of nonequilibrium work and fluctuation theorems, and an earlier, analogous result obtained by Bochkov and Kuzovlev [Zh. Eksp. Teor. Fiz. 72(1), 238247 (1977)]. Both results quantify irreversible behavior by comparing probabilities of observing particular microscopic trajectories during thermodynamic processes related by time-reversal, and both are expressed in terms of the work performed when driving the system away from equilibrium. By deriving these two predictions within a single, Hamiltonian framework, we clarify the precise relationship between them, and discuss how the different definitions of work used by the two sets of authors gives rise to different physical interpretations. We then obtain a extended fluctuation relation that contains both the Crooks and the Bochkov-Kuzovlev results as special cases.Comment: 14 pages with 1 figure, accepted for publication in the Journal of Statistical Mechanic

MALT-45: A 7mm survey of the southern Galaxy - II. ATCA follow-up observations of 44GHz class I methanol masers

We detail interferometric observations of 44 GHz class I methanol masers detected by MALT-45 (a 7 mm unbiased auto-correlated spectral-line Galactic-plane survey) using the Australia Telescope Compact Array. We detect 238 maser spots across 77 maser sites. Using high-resolution positions, we compare the class I CH3OH masers to other star formation maser species, including CS (1–0), SiO v = 0 and the H53 α radio-recombination line. Comparison between the cross- and auto-correlated data has allowed us to also identify quasi-thermal emission in the 44 GHz class I methanol maser line. We find that the majority of class I methanol masers have small spatial and velocity ranges (<0.5 pc and <5 km s−1), and closely trace the systemic velocities of associated clouds. Using 870 μm dust continuum emission from the ATLASGAL survey, we determine clump masses associated with class I masers, and find that they are generally associated with clumps between 1000 and 3000 M⊙. For each class I methanol maser site, we use the presence of OH masers and radio recombination lines to identify relatively evolved regions of high-mass star formation; we find that maser sites without these associations have lower luminosities and preferentially appear towards dark infrared regions

Exact formula for currents in strongly pumped diffusive systems

We analyze a generic model of mesoscopic machines driven by the nonadiabatic variation of external parameters. We derive a formula for the probability current; as a consequence we obtain a no-pumping theorem for cyclic processes satisfying detailed balance and demonstrate that the rectification of current requires broken spatial symmetry.Comment: 10 pages, accepted for publication in the Journal of Statistical Physic

The Next Generation Virgo Cluster Survey. X. Properties of Ultra-Compact Dwarfs in the M87, M49 and M60 Regions

We use imaging from the Next Generation Virgo cluster Survey (NGVS) to present a comparative study of ultra-compact dwarf (UCD) galaxies associated with three prominent Virgo sub-clusters: those centered on the massive, red-sequence galaxies M87, M49 and M60. We show how UCDs can be selected with high completeness using a combination of half-light radius and location in color-color diagrams ($u^*iK_s$ or $u^*gz$). Although the central galaxies in each of these sub-clusters have nearly identical luminosities and stellar masses, we find large differences in the sizes of their UCD populations, with M87 containing ~3.5 and 7.8 times more UCDs than M49 and M60, respectively. The relative abundance of UCDs in the three regions scales in proportion to sub-cluster mass, as traced by X-ray gas mass, total gravitating mass, number of globular clusters, and number of nearby galaxies. We find that the UCDs are predominantly blue in color, with ~85% of the UCDs having colors similar to blue GCs and stellar nuclei of dwarf galaxies. We present evidence that UCDs surrounding M87 and M49 may follow a morphological sequence ordered by the prominence of their outer, low surface brightness envelope, ultimately merging with the sequence of nucleated low-mass galaxies, and that envelope prominence correlates with distance from either galaxy. Our analysis provides evidence that tidal stripping of nucleated galaxies is an important process in the formation of UCDs.Comment: 37 pages, 40 figures. To appear in The Astrophysical Journa

The Next Generation Virgo Cluster Survey. VIII. The Spatial Distribution of Globular Clusters in the Virgo Cluster

We report on a large-scale study of the distribution of globular clusters (GCs) throughout the Virgo cluster, based on photometry from the Next Generation Virgo Cluster Survey, a large imaging survey covering Virgo's primary subclusters to their virial radii. Using the g', (g'-i') color-magnitude diagram of unresolved and marginally-resolved sources, we constructed 2-D maps of the GC distribution. We present the clearest evidence to date showing the difference in concentration between red and blue GCs over the extent of the cluster, where the red (metal-rich) GCs are largely located around the massive early-type galaxies, whilst the blue (metal-poor) GCs have a more extended spatial distribution, with significant populations present beyond 83' (215 kpc) along the major axes of M49 and M87. The GC distribution around M87 and M49 shows remarkable agreement with the shape, ellipticity and boxiness of the diffuse light surrounding both galaxies. We find evidence for spatial enhancements of GCs surrounding M87 that may be indicative of recent interactions or an ongoing merger history. We compare the GC map to the locations of Virgo galaxies and the intracluster X-ray gas, and find good agreement between these baryonic structures. The Virgo cluster contains a total population of 67300$\pm$14400 GCs, of which 35% are located in M87 and M49 alone. We compute a cluster-wide specific frequency S_N,CL=$2.8\pm0.7$, including Virgo's diffuse light. The GC-to-baryonic mass fraction is e_b=$5.7\pm1.1\times10^{-4}$and the GC-to-total cluster mass formation efficiency is e_t=$2.9\pm0.5\times10^{-5}$, values slightly lower than, but consistent with, those derived for individual galactic halos. Our results show that the production of the complex structures in the unrelaxed Virgo cluster core (including the diffuse intracluster light) is an ongoing process.(abridged)Comment: 23 pages, 17 figures. Accepted for publication in the Astrophysical Journal. Figure 1 has reduced resolution. Revised version with updated references, corrected typos -- no changes to result