Recurrent acquisition of cytosine methyltransferases into eukaryotic retrotransposons

Transposable elements are in a constant arms race with the silencing mechanisms of their host genomes. One silencing mechanism commonly used by many eukaryotes is dependent on cytosine methylation, a covalent modification of DNA deposited by C5 cytosine methyltransferases (DNMTs). Here, we report how two distantly related eukaryotic lineages, dinoflagellates and charophytes, have independently incorporated DNMTs into the coding regions of distinct retrotransposon classes. Concomitantly, we show that dinoflagellates of the genus Symbiodinium have evolved cytosine methylation patterns unlike any other eukaryote, with most of the genome methylated at CG dinucleotides. Finally, we demonstrate the ability of retrotransposon DNMTs to methylate CGs de novo, suggesting that retrotransposons could self-methylate retrotranscribed DNA. Together, this is an example of how retrotransposons incorporate host-derived genes involved in DNA methylation. In some cases, this event could have implications for the composition and regulation of the host epigenomic environment

Drought impact on forest carbon dynamics and fluxes in Amazonia

In 2005 and 2010 the Amazon basin experienced two strong droughts, driven by shifts in the tropical hydrological regime possibly associated with global climate change, as predicted by some global models. Tree mortality increased after the 2005 drought, and regional atmospheric inversion modelling showed basin-wide decreases in CO2 uptake in 2010 compared with 2011 (ref. 5). But the response of tropical forest carbon cycling to these droughts is not fully understood and there has been no detailed multi-site investigation in situ. Here we use several years of data from a network of thirteen 1-ha forest plots spread throughout South America, where each component of net primary production (NPP), autotrophic respiration and heterotrophic respiration is measured separately, to develop a better mechanistic understanding of the impact of the 2010 drought on the Amazon forest. We find that total NPP remained constant throughout the drought. However, towards the end of the drought, autotrophic respiration, especially in roots and stems, declined significantly compared with measurements in 2009 made in the absence of drought, with extended decreases in autotrophic respiration in the three driest plots. In the year after the drought, total NPP remained constant but the allocation of carbon shifted towards canopy NPP and away from fine-root NPP. Both leaf-level and plot-level measurements indicate that severe drought suppresses photosynthesis. Scaling these measurements to the entire Amazon basin with rainfall data, we estimate that drought suppressed Amazon-wide photosynthesis in 2010 by 0.38 petagrams of carbon (0.23-0.53 petagrams of carbon). Overall, we find that during this drought, instead of reducing total NPP, trees prioritized growth by reducing autotrophic respiration that was unrelated to growth. This suggests that trees decrease investment in tissue maintenance and defence, in line with eco-evolutionary theories that trees are competitively disadvantaged in the absence of growth. We propose that weakened maintenance and defence investment may, in turn, cause the increase in post-drought tree mortality observed at our plots.Gordon and Betty Moore FoundationNatural Environment Research Council (NERC)EU FP7 Amazalert (282664) projectEU FP7GEOCARBON (283080) projectNational Council for Scientific and Technological Development (CNPq, Brazil)ARC - fellowship awardERC - Advanced Investigator AwardRoyal Society - Wolfson Research Merit AwardJackson FoundationJohn Fell Fun

Development, standardization and refinement of procedures for evaluating effects of endocrine active compounds on development and sexual differentiation of Xenopus laevis

Xenopus laevis has been introduced as a model to study effects of endocrine-active compounds (EAC) on development and sexual differentiation. However, variable and inconsistent data have raised questions about the reliability of the test methods applied. The current study was conducted in two laboratories to develop, refine, and standardize procedures and protocols. Larvae were exposed in flow-through systems to 17β-estradiol (E2), at concentrations from 0.2 to 6.0 μg E2 L−1 in Experiment 1A, and 0.015 to 2.0 μg E2 L−1 in Experiment 1B. In both studies survival (92%, 99%) and percentage of animals that completed metamorphosis (97%, 99%) indicated reproducible biological performance. Furthermore, minor variations in husbandry led to significant differences in snout-to-vent length, weight, and gonad size. In Experiment 1A, almost complete feminization occurred in all E2 treatment groups whereas a concentration response was observed in Experiment 1B resulting in an EC50 of 0.12 μg E2 L−1. The final verified protocol is suitable for determining effects of EAC on development and sexual differentiation in X. laevis

Above- and below-ground net primary productivity across ten Amazonian forests on contrasting soils

Copyright © 2009 European Geosciences Union. This is the published version available at http://www.biogeosciences.net/6/2759/2009/bg-6-2759-2009.html © Author(s) 2009. This work is distributed under the Creative Commons Attribution 3.0 License.The net primary productivity (NPP) of tropical forests is one of the most important and least quantified components of the global carbon cycle. Most relevant studies have focused particularly on the quantification of the above-ground coarse wood productivity, and little is known about the carbon fluxes involved in other elements of the NPP, the partitioning of total NPP between its above- and below-ground components and the main environmental drivers of these patterns. In this study we quantify the above- and below-ground NPP of ten Amazonian forests to address two questions: (1) How do Amazonian forests allocate productivity among its above- and below-ground components? (2) How do soil and leaf nutrient status and soil texture affect the productivity of Amazonian forests? Using a standardized methodology to measure the major elements of productivity, we show that NPP varies between 9.3±1.3MgC ha−1 yr−1 (mean±standard error), at a white sand plot, and 17.0±1.4MgC ha−1 yr−1 at a very fertile Terra Preta site, with an overall average of 12.8±0.9MgC ha−1 yr−1. The studied forests allocate on average 64±3% and 36±3% of the total NPP to the above and below-ground components, respectively. The ratio of above-ground and below-ground NPP is almost invariant with total NPP. Litterfall and fine root production both increase with total NPP, while stem production shows no overall trend. Total NPP tends to increase with soil phosphorus and leaf nitrogen status. However, allocation of NPP to below-ground shows no relationship to soil fertility, but appears to decrease with the increase of soil clay content

Imaging in the time of NFD/NSF: do we have to change our routines concerning renal insufficiency?

To date there are potential chronology-based but not conclusive reasons to believe that at least some of the gadolinium complexes play a causative role in the pathophysiology of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). Still, the exact pathogenesis and the risk for patients is unclear beside the obvious connection to moderate to severe renal insufficiency. So far, MR imaging with Gd-enhancement was regarded as the safest imaging modality in these patients—the recent development creates tremendous uncertainty in the MR-community. Nevertheless, one should remember that, despite the over 200 cases of NSF and about 100 with proven involvement of Gd3+, the vast majority of over 200 million patients exposed to gadolinium since the 1980s have tolerated these agents well. Importantly, NSF is a rare disease and does not appear to occur in patients without renal impairment. Many patients and researchers have undergone MR investigations with Gd exposure in the past. For those, it is essential to know about the safety of the agents at normal renal function. We can hope that pharmacoepidemiological and preclinical studies will allow us to better understand the pathophysiology and role of the various MR contrast agents in the near future

Epidermal growth factor receptor dimerization status determines skin toxicity to HER-kinase targeted therapies

Skin toxicity, a common drug-related adverse event observed in cancer patients treated with epidermal growth factor receptor (EGFR)-directed therapies is rarely seen with therapies targeting HER2. This study reports the significance of the EGFR and HER2 dimerization status in skin with regard to these dermatologic side effects. We demonstrate the differential effect of HER-directed therapies on the ligand driven activation status of EGFR, HER2 and MAPK in normal human epidermal keratinocytes. EGFR-directed therapies, such as gefitinib and cetuximab, inhibited ligand-induced activation of EGFR and MAPK in human keratinocytes. Pertuzumab, an antibody interfering with functional HER2 heterodimerization, failed to block ligand-induced HER signaling in primary keratinocytes. Using a novel proximity-based dimerization assay (eTag™) we show that EGFR homodimers are the predominant HER dimer pair in normal primary kertinocytes and in normal skin tissue from 16 patients with solid malignancies. The presence of [p]EGFR and [p]MAPK, but the absence of [p]HER2, demonstrates productive signaling via EGFR but not HER2 in human skin. These data illustrate the importance of the EGFR dimerization partner in human skin and suggests that inhibition of EGFR homodimer signaling rather than EGFR/HER2 heterodimer signaling maybe the key molecular event determining dermatologic toxicity discrepancies observed between EGFR-targeted versus HER2-targeted therapies

Exclusion of known gene for enamel development in two Brazilian families with amelogenesis imperfecta

Amelogenesis imperfecta (AI) is a genetically heterogeneous group of diseases that result in defective development of tooth enamel. Mutations in several enamel proteins and proteinases have been associated with AI. The object of this study was to evaluate evidence of etiology for the six major candidate gene loci in two Brazilian families with AI. Genomic DNA was obtained from family members and all exons and exon-intron boundaries of the ENAM, AMBN, AMELX, MMP20, KLK4 and Amelotin gene were amplified and sequenced. Each family was also evaluated for linkage to chromosome regions known to contain genes important in enamel development. The present study indicates that the AI in these two families is not caused by any of the known loci for AI or any of the major candidate genes proposed in the literature. These findings indicate extensive genetic heterogeneity for non-syndromic AI

A survey of failed post-retained restorations

Survival of endodontically treated, post-restored teeth depends on a multitude of factors, all of which are practically impossible to include in a randomized, controlled clinical study. The purpose of this survey was to characterize and analyze reported failures of post-retained restorations to identify factors critical to failure and to type of failure. A questionnaire was mailed to private practitioners in Denmark with a request to complete the questionnaire whenever a patient presented with a failed post-retained restoration. Information was gathered on factors related to the patient, the tooth, the restorative materials, and the techniques. Two-hundred and sixty questionnaires were collected from 171 practitioners over a 3-year period. Functioning time until failure varied between 3 months and 38 years. Mean survival time until failure was 11 years. Of the failed restorations, 61% had functioned for 10 years or less. Fracture of the tooth was the most common type of failure reported, followed by loosening of the post and fracture of the post. Tapered posts implied an increased risk of tooth fracture compared to loosening or fracture of the post, and the relative risk of tooth fracture increased with the functioning time until failure. Fracture of the post was more common among male than female patients. On the basis of this survey of failed post-retained restorations, it was concluded that tapered posts were associated with a higher risk of tooth fracture than were parallel-sided posts