The development of the enteric nervous system is dependent upon the actions of glial cell line-derived neurotrophic factor (GDNF) on neural crest-derived precursor cells in the embryonic gut. GDNF ...treatment of cultured enteric precursor cells leads to an increase in the number of neurons that develop and/or survive. Here we demonstrate that, although GDNF promoted an increase in neuron number at all embryonic ages examined, there was a developmental shift from a mitogenic to a trophic response by the developing enteric neurons. The timing of this shift corresponded to developmental changes in gut expression of GFR alpha-1, a co-receptor in the GDNF-Ret signaling complex. GFR alpha-1 was broadly expressed in the gut at early developmental stages, at which times soluble GFR alpha-1 was released into the medium by cultured gut cells. At later times, GFR alpha-1 became restricted to neural crest-derived cells. GFR alpha-1 could participate in GDNF signaling when expressed in cis on the surface of enteric precursor cells, or as a soluble protein. The GDNF-mediated response was greater when cell surface, compared with soluble, GFR alpha-1 was present, with the maximal response seen the presence of both cis and trans forms of GFR alpha-1. In addition to contributing to GDNF signaling, cell-surface GFR alpha-1 modulated the specificity of interactions between GDNF and soluble GFR alphas. These experiments demonstrate that complex, developmentally regulated, signaling interactions contribute to the GDNF-dependent development of enteric neurons.
Two snakes were presented to the Pennsylvania State University Animal Diagnostic Laboratory with one suffering from external lesions where the scales were raised and discolored, and the other with ...oral lesions and swelling extending to the left eye, which was opaque. Histopathological analysis revealed multifocal granulomas containing fungal hyphae. Morphological and DNA sequence analyses revealed both suffered from infection by Ophidiomyces ophiodiicola, an emerging pathogen of snakes. This is the first report of this disease in Pennsylvania.
Context. NGC 4815 is a populous ~500 Myr open cluster at Rgc ~ 7 kpc observed in the first six months of the Gaia-ESO Survey. Located in the inner Galactic disk, NGC 4815 is an important potential ...tracer of the abundance gradient, where relatively few intermediate age open clusters are found. Aims. The Gaia-ESO Survey data can provide an improved characterization of the cluster properties, such as age, distance, reddening, and abundance profile. Methods. We use the survey derived radial velocities, stellar atmospheric parameters, metallicity, and elemental abundances for stars targeted as potential members of this cluster to carry out an analysis of cluster properties. The radial velocity distribution of stars in the cluster field is used to define the cluster systemic velocity and derive likely cluster membership for stars observed by the Gaia-ESO Survey. We investigate the distributions of Fe and Fe-peak elements, alpha-elements, and the light elements Na and Al and characterize the cluster’s internal chemical homogeneity comparing it to the properties of radial velocity non-member stars. Utilizing these cluster properties, the cluster color-magnitude diagram is analyzed and theoretical isochrones are fit to derive cluster reddening, distance, and age. Results. NGC 4815 is found to have a mean metallicity of Fe/H = +0.03 ± 0.05 dex (s.d.). Elemental abundances of cluster members show typically very small internal variation, with internal dispersions of ~0.05 dex. The alpha-elements Ca/Fe and Si/Fe show solar ratios, but Mg/Fe is moderately enhanced, while Ti/Fe appears slightly deficient. As with many open clusters, the light elements Na/Fe and Al/Fe are enhanced, Na/Fe significantly so, although the role of internal mixing and the assumption of local thermodynamical equilibrium in the analysis remain to be investigated. From isochrone fits to color-magnitude diagrams, we find a cluster age of 0.5 to 0.63 Gyr, a reddening of E(B − V) = 0.59 to 0.65, and a distance modulus (m − M)0 = 11.95 to 12.20, depending on the choice of theoretical models, leading to a Galactocentric distance of 6.9 kpc.
Social behaviour may enable organisms to occupy ecological niches that would otherwise be unavailable to them. Here, we test this major evolutionary principle by demonstrating self-organizing social ...behaviour in the plant-animal, Symsagittifera roscoffensis. These marine aceol flat worms rely for all of their nutrition on the algae within their bodies: hence their common name. We show that individual worms interact with one another to coordinate their movements so that even at low densities they begin to swim in small polarized groups and at increasing densities such flotillas turn into circular mills. We use computer simulations to: (i) determine if real worms interact socially by comparing them with virtual worms that do not interact and (ii) show that the social phase transitions of the real worms can occur based only on local interactions between and among them. We hypothesize that such social behaviour helps the worms to form the dense biofilms or mats observed on certain sun-exposed sandy beaches in the upper intertidal of the East Atlantic and to become in effect a super-organismic seaweed in a habitat where macro-algal seaweeds cannot anchor themselves. Symsagittifera roscoffensis, a model organism in many other areas in biology (including stem cell regeneration), also seems to be an ideal model for understanding how individual behaviours can lead, through collective movement, to social assemblages.
We have determined stellar parameters and abundances for 221 giant branch stars in the globular cluster omega Centauri. A combination of photometry and lower resolution spectroscopy was used to ...determine temperature, gravity, metallicity, C/Fe, N/Fe and Ba/Fe. These abundances agree well with those found by previous researchers and expand the analysed sample of the cluster. k-means clustering analysis was used to group the stars into four homogeneous groups based upon these abundances. These stars show the expected anticorrelation between C/Fe and N/Fe. We investigated the distribution of CN-weak/CN-strong stars on the colour-magnitude diagram. Asymptotic giant branch stars, which were selected from their position on the colour-magnitude diagram, were almost all CN weak. This is in contrast to the red giant branch where a large minority were CN strong. The results were also compared with cluster formation and evolution models. Overall, this study shows that statistically significant elemental and evolutionary conclusions can be obtained from lower resolution spectroscopy. PUBLICATION ABSTRACT
Children with cerebral palsy frequently grow poorly. The purpose of this study was to describe observed growth patterns and their relationship to health and social participation in a representative ...sample of children with moderate-severe cerebral palsy.
In a 6-site, multicentered, region-based cross-sectional study, multiple sources were used to identify children with moderate or severe cerebral palsy. There were 273 children enrolled, 58% male, 71% white, with Gross Motor Function Classification System levels III (22%), IV (25%), or V (53%). Anthropometric measures included: weight, knee height, upper arm length, midupper arm muscle area, triceps skinfold, and subscapular skinfold. Intraobserver and interobserver reliability was established. Health care use (days in bed, days in hospital, and visits to doctor or emergency department) and social participation (days missed of school or of usual activities for child and family) over the preceding 4 weeks were measured by questionnaire. Growth curves were developed and z scores calculated for each of the 6 measures. Cluster analysis methodology was then used to create 3 distinct groups of subjects based on average z scores across the 6 measures chosen to provide an overview of growth.
Gender-specific growth curves with 10th, 25th, 50th, 75th, and 90th percentiles for each of the 6 measurements were created. Cluster analyses identified 3 clusters of subjects based on their average z scores for these measures. The subjects with the best growth had fewest days of health care use and fewest days of social participation missed, and the subjects with the worst growth had the most days of health care use and most days of participation missed.
Growth patterns in children with cerebral palsy were associated with their overall health and social participation. The role of these cerebral palsy-specific growth curves in clinical decision-making will require further study.
Overexpression of HER2, a receptor tyrosine kinase of the ERBB family, in breast cancer is related to increased cancer progression and aggressiveness. A breast epithelial cell model with the single ...perturbation of HER2 overexpression is capable of replicating the increased aggressiveness of HER2 overexpressing cancers. In previous work, Wolf-Yadlin and colleagues (Wolf-Yadlin et al., Mol. Syst. Biol., 2006, 2) measured the proximal tyrosine phosphorylation dynamics of the parental and HER2 overexpressing cells (24H) in response to EGF. Here, we apply an ensemble clustering approach to dynamic phosphorylation measurements of the two cell models in order to identify signaling events that explain the increased migratory potential of HER2 overexpressing cells. The use of an ensemble approach for identifying relationships within a dataset and how these relationships change across datasets uncovers relationships that cannot be found by the direct comparison of dynamic responses in the two conditions. Of particular note is a drastic change in the clustering of SHC1 phosphorylation (on site Y349) from an EGFR-MAPK module in parental cells to a module consisting of an E-cadherin junction protein phosphorylation site, catenin delta-1 Y228, in HER2 overexpressing (24H) cells. Given the importance of E-cadherin junctions in healthy epithelial wound healing and migration, we chose to test the computationally-derived identification of altered cell junctions and CTNND1:SHC1 relationships. Our cell and molecular biology experiments demonstrate that SHC and CTNND1 interact in an EGF- and HER2-dependent manner and that the cell junctions are phenotypically affected by HER2, breaking down in response to EGF and yet avoiding apoptosis as a result of cell junction loss. The results suggest a mechanism by which HER2 alters the localization of the SHC-MAPK signaling axis and a phenotypic effect on cell junction integrity.
Two plutonium oxides were prepared as unique reference materials for measurement of actinide elements present as trace constituents. Each reference material unit is approximately 200 mg of PuO
powder ...in a quartz glass bottle. Characterized attributes of the oxides included mass fractions of plutonium, americium, neptunium, and uranium. Isotope-amount ratios were also determined for plutonium and uranium, but neptunium and americium were observed to be monoisotopic
Np and
Am. Measurements for characterization and verification of the attributes show that plutonium and trace actinides are homogeneous with the exception of limited heterogeneity for uranium, primarily observed for the
U isotope. Model purification ages calculated from measured americium and uranium attribute values are consistent with material histories and indicate that these impurities are predominantly due to the decay of plutonium isotopes.
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