The mechanisms and mediators of tooth eruption--models for developmental biologists

Tooth eruption is a localized process in the jaws which exhibits precise timing and bilateral symmetry. It involves resorption and formation of bone on opposite sides of the erupting tooth and these activities depend on the dental follicle, a thin connective tissue investment of the developing and erupting tooth. Biochemical studies have shown that during eruption cells, proteins and enzymes change in the dental follicle and several growth factors and proteins known to accelerate or retard eruption have been identified. This review discusses these aspects of tooth eruption and proposes testable hypotheses and strategies that can make studies of tooth eruption new experimental opportunities for developmental biologists

Deformed General Relativity and Torsion

We argue that the natural framework for embedding the ideas of deformed, or doubly, special relativity (DSR) into a curved spacetime is a generalisation of Einstein-Cartan theory, considered by Stelle and West. Instead of interpreting the noncommuting "spacetime coordinates" of the Snyder algebra as endowing spacetime with a fundamentally noncommutative structure, we are led to consider a connection with torsion in this framework. This may lead to the usual ambiguities in minimal coupling. We note that observable violations of charge conservation induced by torsion should happen on a time scale of 10^3 s, which seems to rule out these modifications as a serious theory. Our considerations show, however, that the noncommutativity of translations in the Snyder algebra need not correspond to noncommutative spacetime in the usual sense.Comment: 20 pages, 1 figure, revtex; expanded sections 3 and 4 for clarity, moved material to appendix B, corrected a few minor error

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

\u3cem\u3eHerschel\u3c/em\u3e Observations of FIR Emission Lines in Brightest Cluster Galaxies

The question of how much gas cools in the cores of clusters of galaxies has been the focus of many, multiwavelength studies in the past 30 years. In this letter we present the first detections of the strongest atomic cooling lines, [Cii], [Oi] and [Nii] in two strong cooling flow clusters, A1068 and A2597, using Herschel-PACS. These spectra indicate that the substantial mass of cold molecular gas (\u3e 109 M⊙) known to be present in these systems is being irradiated by intense UV radiation, most probably from young stars. The line widths of these FIR lines indicate that they share dynamics similar but not identical to other ionised and molecular gas traced by optical, near-infrared and CO lines. The relative brightness of the FIR lines compared to CO and FIR luminosity is consistent with other star-forming galaxies indicating that the properties of the molecular gas clouds in cluster cores and the stars they form are not unusual. These results provide additional evidence for a reservoir of cold gas that is fed by the cooling of gas in the cores of the most compact clusters and provide important diagnostics of the temperature and density of the dense clouds this gas resides in

\u3cem\u3eHerschel\u3c/em\u3e Photometry of Brightest Cluster Galaxies in Cooling Flow Clusters

The dust destruction timescales in the cores of clusters of galaxies are relatively short given their high central gas densities. However, substantial mid-infrared and sub-mm emission has been detected in many brightest cluster galaxies. In this letter we present Herschel PACS and SPIRE photometry of the brightest cluster galaxy in three strong cooling flow clusters, A1068, A2597 and Zw3146. This photometry indicates that a substantial mass of cold dust is present (\u3e 3×107 M⊙) at temperatures significantly lower (20–28 K) than previously thought based on limited MIR and/or sub-mm results. The mass and temperature of the dust appear to match those of the cold gas traced by CO with a gas-to-dust ratio of 80–120

The Hordeum Toolbox: The Barley Coordinated Agricultural Project Genotype and Phenotype Resource

The use of DNA markers in public sector plant breeding is now the norm. Such markers are common across breeding programs and this commonality enables and enhances collaboration. Therefore, large collaborative research projects that measure several phenotypes across multiple environments coupled with the expanding amount of genotype data attainable with current marker technologies are on the rise and these projects demand efficient data delivery. However, development of computational tools for advanced data integration, visualization, and analysis is still a bottleneck, even though these resources have the greatest potential impact for users who are extracting and developing hypothesis-based solutions. The Hordeum Toolbox (THT) was developed as a data resource for the Barley Coordinated Agricultural Project (CAP) with the novel capability of constructing user-defined downloadable sets of phenotype and/or genotype data for downstream analysis. Internal tools in THT enable users to create clusters of a selected group of lines based on genotype data, parse pedigrees, and select germplasm based on haplotype, phenotype, and agronomic properties. The Hordeum Toolbox can be adapted to breeding programs or collaborations to assist researchers in germplasm selection, genotype data visualization, and the integration of complex data sets for statistical analysisThis is the publisher’s final pdf. The published article is copyrighted by the Crop Science Society of America and can be found at: https://www.crops.org/publications/tp

Fishing the Molecular Bases of Treacher Collins Syndrome

Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development, and mutations in the TCOF1 gene are responsible for over 90% of TCS cases. The knowledge about the molecular mechanisms responsible for this syndrome is relatively scant, probably due to the difficulty of reproducing the pathology in experimental animals. Zebrafish is an emerging model for human disease studies, and we therefore assessed it as a model for studying TCS. We identified in silico the putative zebrafish TCOF1 ortholog and cloned the corresponding cDNA. The derived polypeptide shares the main structural domains found in mammals and amphibians. Tcof1 expression is restricted to the anterior-most regions of zebrafish developing embryos, similar to what happens in mouse embryos. Tcof1 loss-of-function resulted in fish showing phenotypes similar to those observed in TCS patients, and enabled a further characterization of the mechanisms underlying craniofacial malformation. Besides, we initiated the identification of potential molecular targets of treacle in zebrafish. We found that Tcof1 loss-of-function led to a decrease in the expression of cellular proliferation and craniofacial development. Together, results presented here strongly suggest that it is possible to achieve fish with TCS-like phenotype by knocking down the expression of the TCOF1 ortholog in zebrafish. This experimental condition may facilitate the study of the disease etiology during embryonic development

We should not be complacent about our population-based public health response to the first influenza pandemic of the 21st century

Background: More than a year after an influenza pandemic was declared in June 2009, the World Health Organization declared the pandemic to be over. Evaluations of the pandemic response are beginning to appear in the public domain. Discussion. We argue that, despite the enormous effort made to control the pandemic, it is now time to acknowledge that many of the population-based public health interventions may not have been well considered. Prior to the pandemic, there was limited scientific evidence to support border control measures. In particular no border screening measures would have detected prodromal or asymptomatic infections, and asymptomatic infections with pandemic influenza were common. School closures, when they were partial or of short duration, would not have interrupted spread of the virus in school-aged children, the group with the highest rate of infection worldwide. In most countries where they were available, neuraminidase inhibitors were not distributed quickly enough to have had an effect at the population level, although they will have benefited individuals, and prophylaxis within closed communities will have been effective. A pandemic specific vaccine will have protected the people who received it, although in most countries only a small minority was vaccinated, and often a small minority of those most at risk. The pandemic vaccine was generally not available early enough to have influenced the shape of the first pandemic wave and it is likely that any future pandemic vaccine manufactured using current technology will also be available too late, at least in one hemisphere. Summary. Border screening, school closure, widespread anti-viral prophylaxis and a pandemic-specific vaccine were unlikely to have been effective during a pandemic which was less severe than anticipated in the pandemic plans of many countries. These were cornerstones of the population-based public health response. Similar responses would be even less likely to be effective in a more severe pandemic. We agree with the recommendation from the World Health Organisation that pandemic preparedness plans need review