Cell adhesion molecule cadherin-6 function in zebrafish cranial and lateral line ganglia development

Cadherins regulate the vertebrate nervous system development. We previously showed that cadherin-6 message (cdh6) was strongly expressed in the majority of the embryonic zebrafish cranial and lateral line ganglia during their development. Here, we present evidence that cdh6 has specific functions during cranial and lateral line ganglia and nerve development. We analyzed the consequences of cdh6 loss-of-function on cranial ganglion and nerve differentiation in zebrafish embryos. Embryos injected with zebrafish cdh6 specific antisense morpholino oligonucleotides (MOs, which suppress gene expression during development; cdh6 morphant embryos) displayed a specific phenotype, including (i) altered shape and reduced development of a subset of the cranial and lateral line ganglia (e.g., the statoacoustic ganglion and vagal ganglion) and (ii) cranial nerves were abnormally formed. These data illustrate an important role for cdh6 in the formation of cranial ganglia and their nerves

Quantifying the impact of an extreme climate event on species diversity in fragmented temperate forests: the effect of the October 1987 storm on British broadleaved woodlands

We report the impact of an extreme weather event, the October 1987 severe storm, on fragmented woodlands in southern Britain. We analysed ecological changes between 1971 and 2002 in 143 200-m2 plots in 10 woodland sites exposed to the storm with an ecologically equivalent sample of 150 plots in 16 non-exposed sites. Comparing both years, understorey plant species-richness, species composition, soil pH and woody basal area of the tree and shrub canopy were measured. We tested the hypothesis that the storm had deflected sites from the wider national trajectory of an increase in woody basal area and reduced understorey species-richness associated with ageing canopies and declining woodland management. We also expected storm disturbance to amplify the background trend of increasing soil pH, a UK-wide response to reduced atmospheric sulphur deposition. Path analysis was used to quantify indirect effects of storm exposure on understorey species richness via changes in woody basal area and soil pH. By 2002, storm exposure was estimated to have increased mean species richness per 200 m2 by 32%. Woody basal area changes were highly variable and did not significantly differ with storm exposure. Increasing soil pH was associated with a 7% increase in richness. There was no evidence that soil pH increased more as a function of storm exposure. Changes in species richness and basal area were negatively correlated: a 3.4% decrease in richness occurred for every 0.1-m2 increase in woody basal area per plot. Despite all sites substantially exceeding the empirical critical load for nitrogen deposition, there was no evidence that in the 15 years since the storm, disturbance had triggered a eutrophication effect associated with dominance of gaps by nitrophilous species. Synthesis. Although the impacts of the 1987 storm were spatially variable in terms of impacts on woody basal area, the storm had a positive effect on understorey species richness. There was no evidence that disturbance had increased dominance of gaps by invasive species. This could change if recovery from acidification results in a soil pH regime associated with greater macronutrient availability."Organismic and Evolutionary Biolog

Randomized Trial of Introduction of Allergenic Foods in Breast-Fed Infants.

BACKGROUND: The age at which allergenic foods should be introduced into the diet of breast-fed infants is uncertain. We evaluated whether the early introduction of allergenic foods in the diet of breast-fed infants would protect against the development of food allergy. METHODS: We recruited, from the general population, 1303 exclusively breast-fed infants who were 3 months of age and randomly assigned them to the early introduction of six allergenic foods (peanut, cooked egg, cow's milk, sesame, whitefish, and wheat; early-introduction group) or to the current practice recommended in the United Kingdom of exclusive breast-feeding to approximately 6 months of age (standard-introduction group). The primary outcome was food allergy to one or more of the six foods between 1 year and 3 years of age. RESULTS: In the intention-to-treat analysis, food allergy to one or more of the six intervention foods developed in 7.1% of the participants in the standard-introduction group (42 of 595 participants) and in 5.6% of those in the early-introduction group (32 of 567) (P=0.32). In the per-protocol analysis, the prevalence of any food allergy was significantly lower in the early-introduction group than in the standard-introduction group (2.4% vs. 7.3%, P=0.01), as was the prevalence of peanut allergy (0% vs. 2.5%, P=0.003) and egg allergy (1.4% vs. 5.5%, P=0.009); there were no significant effects with respect to milk, sesame, fish, or wheat. The consumption of 2 g per week of peanut or egg-white protein was associated with a significantly lower prevalence of these respective allergies than was less consumption. The early introduction of all six foods was not easily achieved but was safe. CONCLUSIONS: The trial did not show the efficacy of early introduction of allergenic foods in an intention-to-treat analysis. Further analysis raised the question of whether the prevention of food allergy by means of early introduction of multiple allergenic foods was dose-dependent. (Funded by the Food Standards Agency and others; EAT Current Controlled Trials number, ISRCTN14254740.)

Relativistic quantum dynamics in strong fields: Photon emission from heavy, few-electron ions

Recent progress in the study of the photon emission from highly-charged heavy ions is reviewed. These investigations show that high-$Z$ ions provide a unique tool for improving the understanding of the electron-electron and electron-photon interaction in the presence of strong fields. Apart from the bound-state transitions, which are accurately described in the framework of Quantum Electrodynamics, much information has been obtained also from the radiative capture of (quasi-) free electrons by high-$Z$ ions. Many features in the observed spectra hereby confirm the inherently relativistic behavior of even the simplest compound quantum systems in Nature.Comment: Version 18/11/0

HICS: Highly charged ion collisions with surfaces

The layout of a new instrument designed to study the interaction of highly charged ions with surfaces, which consists of an ion source, a beamline including charge separation and a target chamber, is presented here. By varying the charge state and impact velocity of the projectiles separately, the dissipation of potential and kinetic energy at or below the surface can be studied independently. The target chamber offers the use of tunable metal-insulator-metal devices as detectors for internal electronic excitation, a timeof-flight system to study the impact induced particle emission and the possibility to transfer samples in situ to a UHV scanning probe microscope. Samples and detectors can be prepared in situ as well. As a first example data on graphene layers on SrTiO3 which have been irradiated with Xe36+ are presented. Key words: highly charged ions, sputtering, AFM, grapheneComment: 4 pages, 4 figures, conference proceeding to 17th Internat. Workshop for Ion Surf. Collision

Development of the preterm gut microbiome in twins at risk of necrotising enterocolitis and sepsis

The preterm gut microbiome is a complex dynamic community influenced by genetic and environmental factors and is implicated in the pathogenesis of necrotising enterocolitis (NEC) and sepsis. We aimed to explore the longitudinal development of the gut microbiome in preterm twins to determine how shared environmental and genetic factors may influence temporal changes and compared this to the expressed breast milk (EBM) microbiome. Stool samples (n = 173) from 27 infants (12 twin pairs and 1 triplet set) and EBM (n = 18) from 4 mothers were collected longitudinally. All samples underwent PCR-DGGE (denaturing gradient gel electrophoresis) analysis and a selected subset underwent 454 pyrosequencing. Stool and EBM shared a core microbiome dominated by Enterobacteriaceae, Enterococcaceae, and Staphylococcaceae. The gut microbiome showed greater similarity between siblings compared to unrelated individuals. Pyrosequencing revealed a reduction in diversity and increasing dominance of Escherichia sp. preceding NEC that was not observed in the healthy twin. Antibiotic treatment had a substantial effect on the gut microbiome, reducing Escherichia sp. and increasing other Enterobacteriaceae. This study demonstrates related preterm twins share similar gut microbiome development, even within the complex environment of neonatal intensive care. This is likely a result of shared genetic and immunomodulatory factors as well as exposure to the same maternal microbiome during birth, skin contact and exposure to EBM. Environmental factors including antibiotic exposure and feeding are additional significant determinants of community structure, regardless of host genetics

Competitive Regulation of E-Cadherin JuxtaMembrane Domain Degradation by p120-Catenin Binding and Hakai-Mediated Ubiquitination

p120-Catenin binding to, and Hakai-mediated ubiquitination of the E-cadherin juxtamembrane domain (JMD) are thought to be involved in regulating E-cadherin internalization and degradation. However, the relationship between these two pathways is not understood. We targeted the E-cadherin JMD to mitochondria (WT-JMD) to isolate this domain from the plasma membrane and internalization, and to examine protein modifications and degradation. WT-JMD localized to mitochondria, but did not accumulate there except when proteasome activity was inhibited. We found WT-JMD was ubiquitinated, and arginine substitution of lysines at position 5 (K5R) and 83 (K83R) resulted in the stable accumulation of mutant JMD at mitochondria. p120-Catenin did not localize, or bind to WT-JMD even upon proteasome inhibition, whereas the K5,83R-JMD mutant bound and localized p120-catenin to mitochondria. Mutation of the p120-catenin binding site in combination with these lysine mutations inhibited p120-catenin binding, but did not decrease JMD stability or its accumulation at mitochondria. Thus, increased stability of JMD lysine mutants was due to inhibition of ubiquitination and not to p120-catenin binding. Finally, mutation of these critical lysines in full length E-cadherin had similar effects on protein stability as WT-JMD. Our results indicate that ubiquitination of the JMD inhibits p120-catenin binding, and targets E-cadherin for degradation

Learn before Lecture: A Strategy That Improves Learning Outcomes in a Large Introductory Biology Class

Actively engaging students in lecture has been shown to increase learning gains. To create time for active learning without displacing content we used two strategies for introducing material before class in a large introductory biology course. Four to five slides from 2007/8 were removed from each of three lectures in 2009 and the information introduced in preclass worksheets or narrated PowerPoint videos. In class, time created by shifting lecture material to learn before lecture (LBL) assignments was used to engage students in application of their new knowledge. Learning was evaluated by comparing student performance in 2009 versus 2007/8 on LBL-related question pairs, matched by level and format. The percentage of students who correctly answered five of six LBL-related exam questions was significantly higher (p < 0.001) in 2009 versus 2007/8. The mean increase in performance was 21% across the six LBL-related questions compared with <3% on all non-LBL exam questions. The worksheet and video LBL formats were equally effective based on a cross-over experimental design. These results demonstrate that LBLs combined with interactive exercises can be implemented incrementally and result in significant increases in learning gains in large introductory biology classes

Inhibition of sialidase activity and cellular invasion by the bacterial vaginosis pathogen Gardnerella vaginalis

Bacterial vaginosis is a genital tract infection, thought to be caused by transformation of a lactobacillus-rich flora to a dysbiotic microbiota enriched in mixed anaerobes. The most prominent of these is Gardnerella vaginalis (GV), an anaerobic pathogen that produces sialidase enzyme to cleave terminal sialic acid residues from human glycans. Notably, high sialidase activity is associated with preterm birth and low birthweight. We explored the potential of the sialidase inhibitor Zanamavir against GV whole cell sialidase activity using methyl-umbelliferyl neuraminic acid (MU-NANA) cleavage assays, with Zanamavir causing a 30% reduction in whole cell GV sialidase activity (p < 0.05). Furthermore, cellular invasion assays using HeLa cervical epithelial cells, infected with GV, demonstrated that Zanamivir elicited a 50% reduction in cell association and invasion (p < 0.05). Our data thus highlight that pharmacological sialidase inhibitors are able to modify BV-associated sialidase activity and influence host-pathogen interactions and may represent novel therapeutic adjuncts