High specificity of BCL11B and GLG1 for EWSR1-FLI1 and EWSR1-ERG positive Ewing sarcoma

Ewing sarcoma (EwS) is an aggressive cancer displaying an undifferentiated small-round-cell histomorphology that can be easily confused with a broad spectrum of differential diagnoses. Using comparative transcriptomics and immunohistochemistry (IHC), we previously identified BCL11B and GLG1 as potential specific auxiliary IHC markers for EWSR1-FLI1-positive EwS. Herein, we aimed at validating the specificity of both markers in a far larger and independent cohort of EwS (including EWSR1-ERG-positive cases) and differential diagnoses. Furthermore, we evaluated their intra-tumoral expression heterogeneity. Thus, we stained tissue microarrays from 133 molecularly confirmed EwS cases and 320 samples from morphological mimics, as well as a series of patient-derived xenograft (PDX) models for BCL11B, GLG1, and CD99, and systematically assessed the immunoreactivity and optimal cut-offs for each marker. These analyses demonstrated that high BCL11B and/or GLG1 immunoreactivity in CD99-positive cases had a specificity of 97.5% and an accuracy of 87.4% for diagnosing EwS solely by IHC, and that the markers were expressed by EWSR1-ERG-positive EwS. Only little intra-tumoral heterogeneity in immunoreactivity was observed for differential diagnoses. These results indicate that BCL11B and GLG1 may help as specific auxiliary IHC markers in diagnosing EwS in conjunction with CD99, especially if confirmatory molecular diagnostics are not available

The effect of tidal forcing on biogeochemical processes in intertidal salt marsh sediments

<p>Abstract</p> <p>Background</p> <p>Early diagenetic processes involved in natural organic matter (NOM) oxidation in marine sediments have been for the most part characterized after collecting sediment cores and extracting porewaters. These techniques have proven useful for deep-sea sediments where biogeochemical processes are limited to aerobic respiration, denitrification, and manganese reduction and span over several centimeters. In coastal marine sediments, however, the concentration of NOM is so high that the spatial resolution needed to characterize these processes cannot be achieved with conventional sampling techniques. In addition, coastal sediments are influenced by tidal forcing that likely affects the processes involved in carbon oxidation.</p> <p>Results</p> <p>In this study, we used in situ voltammetry to determine the role of tidal forcing on early diagenetic processes in intertidal salt marsh sediments. We compare ex situ measurements collected seasonally, in situ profiling measurements, and in situ time series collected at several depths in the sediment during tidal cycles at two distinct stations, a small perennial creek and a mud flat. Our results indicate that the tides coupled to the salt marsh topography drastically influence the distribution of redox geochemical species and may be responsible for local differences noted year-round in the same sediments. Monitoring wells deployed to observe the effects of the tides on the vertical component of porewater transport reveal that creek sediments, because of their confinements, are exposed to much higher hydrostatic pressure gradients than mud flats.</p> <p>Conclusion</p> <p>Our study indicates that iron reduction can be sustained in intertidal creek sediments by a combination of physical forcing and chemical oxidation, while intertidal mud flat sediments are mainly subject to sulfate reduction. These processes likely allow microbial iron reduction to be an important terminal electron accepting process in intertidal coastal sediments.</p

High Levels of Diversity Uncovered in a Widespread Nominal Taxon: Continental Phylogeography of the Neotropical Tree Frog

Species distributed across vast continental areas and across major biomes provide unique model systems for studies of biotic diversification, yet also constitute daunting financial, logistic and political challenges for data collection across such regions. The tree frog Dendropsophus minutus (Anura: Hylidae) is a nominal species, continentally distributed in South America, that may represent a complex of multiple species, each with a more limited distribution. To understand the spatial pattern of molecular diversity throughout the range of this species complex, we obtained DNA sequence data from two mitochondrial genes, cytochrome oxidase I (COI) and the 16S rhibosomal gene (16S) for 407 samples of D. minutus and closely related species distributed across eleven countries, effectively comprising the entire range of the group. We performed phylogenetic and spatially explicit phylogeographic analyses to assess the genetic structure of lineages and infer ancestral areas. We found 43 statistically supported, deep mitochondrial lineages, several of which may represent currently unrecognized distinct species. One major clade, containing 25 divergent lineages, includes samples from the type locality of D. minutus. We defined that clade as the D. minutus complex. The remaining lineages together with the D. minutus complex constitute the D. minutus species group. Historical analyses support an Amazonian origin for the D. minutus species group with a subsequent dispersal to eastern Brazil where the D. minutus complex originated. According to our dataset, a total of eight mtDNA lineages have ranges >100,000 km2. One of them occupies an area of almost one million km2 encompassing multiple biomes. Our results, at a spatial scale and resolution unprecedented for a Neotropical vertebrate, confirm that widespread amphibian species occur in lowland South America, yet at the same time a large proportion of cryptic diversity still remains to be discovered