The role of cell-cell adhesion in wound healing

We present a stochastic model which describes fronts of cells invading a wound. In the model cells can move, proliferate, and experience cell-cell adhesion. We find several qualitatively different regimes of front motion and analyze the transitions between them. Above a critical value of adhesion and for small proliferation large isolated clusters are formed ahead of the front. This is mapped onto the well-known ferromagnetic phase transition in the Ising model. For large adhesion, and larger proliferation the clusters become connected (at some fixed time). For adhesion below the critical value the results are similar to our previous work which neglected adhesion. The results are compared with experiments, and possible directions of future work are proposed.Comment: to appear in Journal of Statistical Physic

A Chandra Study of the NGC 7618/UGC 12491 Major Group Merger at Apogee: Multiple Cold Fronts, Boxy Wings, Filaments, and Arc-shaped Slingshot Tails

Analyses of major group mergers are key to understanding the evolution of large-scale structure in the Universe and the microphysical properties of the hot gas in these systems. We present imaging and spectral analyses of deep Chandra observations of hot gas structures formed in the major merger of the NGC 7618 and UGC 12491 galaxy groups and compare the observed hot gas morphology, temperatures, and abundances with recent simulations. The morphology of the observed multiple cold front edges and boxy wings are consistent with those expected to be formed by Kelvin–Helmholtz instabilities and gas sloshing in inviscid gas. The arc-shaped slingshot tail morphologies seen in each galaxy suggest that the dominant galaxies are near their orbital apogee after having experienced at least one core passage at a large impact parameter

Extended X-ray study of M49: The frontier of the Virgo cluster

The M49 group, residing outside the virial radius of the Virgo cluster, is falling onto the cluster from the south. We report results from deep XMM-Newton mosaic observations of M49. Its hot gas temperature is 0.8 keV at the group center and rises to 1.5 keV beyond the brightest group galaxy (BGG). The group gas extends to radii of ~300 kpc to the north and south. The observations reveal a cold front ~20 kpc north of the BGG center and an X-ray-bright stripped tail 70 kpc long and 10 kpc wide to the southwest of the BGG. We argue that the atmosphere of the infalling group was slowed by its encounter with the Virgo cluster gas, causing the BGG to move forward subsonically relative to the group gas. We measure declining temperature and metallicity gradients along the stripped tail. The tail gas can be traced back to the cooler and enriched gas uplifted from the BGG center by buoyant bubbles, implying that active galactic nucleus outbursts may have intensified the stripping process. We extrapolate to a virial radius of 740 kpc and derive a virial mass of 4.6 × 1013 M ⊙ for the M49 group. Its group atmosphere appears truncated and deficient when compared with isolated galaxy groups of similar temperatures. If M49 is on its first infall to Virgo, the infall region of a cluster could have profound impacts on galaxies and groups that are being accreted onto galaxy clusters. Alternatively, M49 may have already passed through Virgo once

A Comparison of Parallel Pyrosequencing and Sanger Clone-Based Sequencing and Its Impact on the Characterization of the Genetic Diversity of HIV-1

BACKGROUND: Pyrosequencing technology has the potential to rapidly sequence HIV-1 viral quasispecies without requiring the traditional approach of cloning. In this study, we investigated the utility of ultra-deep pyrosequencing to characterize genetic diversity of the HIV-1 gag quasispecies and assessed the possible contribution of pyrosequencing technology in studying HIV-1 biology and evolution. METHODOLOGY/PRINCIPAL FINDINGS: HIV-1 gag gene was amplified from 96 patients using nested PCR. The PCR products were cloned and sequenced using capillary based Sanger fluorescent dideoxy termination sequencing. The same PCR products were also directly sequenced using the 454 pyrosequencing technology. The two sequencing methods were evaluated for their ability to characterize quasispecies variation, and to reveal sites under host immune pressure for their putative functional significance. A total of 14,034 variations were identified by 454 pyrosequencing versus 3,632 variations by Sanger clone-based (SCB) sequencing. 11,050 of these variations were detected only by pyrosequencing. These undetected variations were located in the HIV-1 Gag region which is known to contain putative cytotoxic T lymphocyte (CTL) and neutralizing antibody epitopes, and sites related to virus assembly and packaging. Analysis of the positively selected sites derived by the two sequencing methods identified several differences. All of them were located within the CTL epitope regions. CONCLUSIONS/SIGNIFICANCE: Ultra-deep pyrosequencing has proven to be a powerful tool for characterization of HIV-1 genetic diversity with enhanced sensitivity, efficiency, and accuracy. It also improved reliability of downstream evolutionary and functional analysis of HIV-1 quasispecies

Sex-Specific Expression of the X-Linked Histone Demethylase Gene Jarid1c in Brain

Jarid1c, an X-linked gene coding for a histone demethylase, plays an important role in brain development and function. Notably, JARID1C mutations cause mental retardation and increased aggression in humans. These phenotypes are consistent with the expression patterns we have identified in mouse brain where Jarid1c mRNA was detected in hippocampus, hypothalamus, and cerebellum. Jarid1c expression and associated active histone marks at its 5′end are high in P19 neurons, indicating that JARID1C demethylase plays an important role in differentiated neuronal cells. We found that XX mice expressed Jarid1c more highly than XY mice, independent of their gonadal types (testes versus ovaries). This increased expression in XX mice is consistent with Jarid1c escape from X inactivation and is not compensated by expression from the Y-linked paralogue Jarid1d, which is expressed at a very low level compared to the X paralogue in P19 cells. Our observations suggest that sex-specific expression of Jarid1c may contribute to sex differences in brain function

Early Loss of Xist RNA Expression and Inactive X Chromosome Associated Chromatin Modification in Developing Primordial Germ Cells

The inactive X chromosome characteristic of female somatic lineages is reactivated during development of the female germ cell lineage. In mouse, analysis of protein products of X-linked genes and/or transgenes located on the X chromosome has indicated that reactivation occurs after primordial germ cells reach the genital ridges.We present evidence that the epigenetic reprogramming of the inactive X-chromosome is initiated earlier than was previously thought, around the time that primordial germ cells (PGCs) migrate through the hindgut. Specifically, we find that Xist RNA expression, the primary signal for establishment of chromosome silencing, is extinguished in migrating PGCs. This is accompanied by displacement of Polycomb-group repressor proteins Eed and Suz(12), and loss of the inactive X associated histone modification, methylation of histone H3 lysine 27.We conclude that X reactivation in primordial germ cells occurs progressively, initiated by extinction of Xist RNA around the time that germ cells migrate through the hindgut to the genital ridges. The events that we observe are reminiscent of X reactivation of the paternal X chromosome in inner cell mass cells of mouse pre-implantation embryos and suggest a unified model in which execution of the pluripotency program represses Xist RNA thereby triggering progressive reversal of epigenetic silencing of the X chromosome

Aurintricarboxylic acid prevents GLUR2 mRNA down-regulation and delayed neurodegeneration in hippocampal CA1 neurons of gerbil after global ischemia

Aurintricarboxylic acid (ATA), an inhibitor of endonuclease activity and other protein–nucleic acid interactions, blocks apoptosis in several cell types and prevents delayed death of hippocampal pyramidal CA1 neurons induced by transient global ischemia. Global ischemia in rats and gerbils induces down-regulation of GluR2 mRNA and increased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-induced Ca(2+) influx in CA1 before neurodegeneration. This result and neuroprotection by antagonists of AMPA receptors suggests that formation of AMPA receptors lacking GluR2, and therefore Ca(2+) permeable, leads to excessive Ca(2+) influx in response to endogenous glutamate; the resulting delayed neuronal death in CA1 exhibits many characteristics of apoptosis. In this study, we examined the effects of ATA on expression of mRNAs encoding glutamate receptor subunits in gerbil hippocampus after global ischemia. Administration of ATA by injection into the right cerebral ventricle 1 h before (but not 6 h after) bilateral carotid occlusion prevented the ischemia-induced decrease in GluR2 mRNA expression and the delayed neurodegeneration. These findings suggest that ATA is neuroprotective in ischemia by blocking the transcriptional changes leading to down-regulation of GluR2, rather than by simply blocking endonucleases, which presumably act later after Ca(2+) influx initiates apoptosis. Maintaining formation of Ca(2+) impermeable, GluR2 containing AMPA receptors could prevent delayed death of CA1 neurons after transient global ischemia, and block of GluR2 down-regulation may provide a further strategy for neuroprotection

FGF4 Independent Derivation of Trophoblast Stem Cells from the Common Vole

The derivation of stable multipotent trophoblast stem (TS) cell lines from preimplantation, and early postimplantation mouse embryos has been reported previously. FGF4, and its receptor FGFR2, have been identified as embryonic signaling factors responsible for the maintenance of the undifferentiated state of multipotent TS cells. Here we report the derivation of stable TS-like cell lines from the vole M. rossiaemeridionalis, in the absence of FGF4 and heparin. Vole TS-like cells are similar to murine TS cells with respect to their morphology, transcription factor gene expression and differentiation in vitro into derivatives of the trophectoderm lineage, and with respect to their ability to invade and erode host tissues, forming haemorrhagic tumours after subcutaneous injection into nude mice. Moreover, vole TS-like cells carry an inactive paternal X chromosome, indicating that they have undergone imprinted X inactivation, which is characteristic of the trophoblast lineage. Our results indicate that an alternative signaling pathway may be responsible for the establishment and stable proliferation of vole TS-like cells