Absence of Runx3 expression in normal gastrointestinal epithelium calls into question its tumour suppressor function

The Runx3 transcription factor regulates cell fate decisions during embryonic development and in adults. It was previously reported that Runx3 is strongly expressed in embryonic and adult gastrointestinal tract (GIT) epithelium (Ep) and that its loss causes gastric cancer. More than 280 publications have based their research on these findings and concluded that Runx3 is indeed a tumour suppressor (TS). In stark contrast, using various measures, we found that Runx3 expression is undetectable in GIT Ep. Employing a variety of biochemical and genetic techniques, including analysis of Runx3-GFP and R26LacZ/Runx3Cre or R26tdTomato/Runx3Cre reporter strains, we readily detected Runx3 in GIT-embedded leukocytes, dorsal root ganglia, skeletal elements and hair follicles. However, none of these approaches revealed detectable Runx3 levels in GIT Ep. Moreover, our analysis of the original Runx3LacZ/LacZ mice used in the previously reported study failed to reproduce the GIT expression of Runx3. The lack of evidence for Runx3 expression in normal GIT Ep creates a serious challenge to the published data and undermines the notion that Runx3 is a TS involved in cancer pathogenesis

Protein interactions in Xenopus germ plasm RNP particles

Hermes is an RNA-binding protein that we have previously reported to be found in the ribonucleoprotein (RNP) particles of Xenopus germ plasm, where it is associated with various RNAs, including that encoding the germ line determinant Nanos1. To further define the composition of these RNPs, we performed a screen for Hermes-binding partners using the yeast two-hybrid system. We have identified and validated four proteins that interact with Hermes in germ plasm: two isoforms of Xvelo1 (a homologue of zebrafish Bucky ball) and Rbm24b and Rbm42b, both RNA-binding proteins containing the RRM motif. GFP-Xvelo fusion proteins and their endogenous counterparts, identified with antisera, were found to localize with Hermes in the germ plasm particles of large oocytes and eggs. Only the larger Xvelo isoform was naturally found in the Balbiani body of previtellogenic oocytes. Bimolecular fluorescence complementation (BiFC) experiments confirmed that Hermes and the Xvelo variants interact in germ plasm, as do Rbm24b and 42b. Depletion of the shorter Xvelo variant with antisense oligonucleotides caused a decrease in the size of germ plasm aggregates and loosening of associated mitochondria from these structures. This suggests that the short Xvelo variant, or less likely its RNA, has a role in organizing and maintaining the integrity of germ plasm in Xenopus oocytes. While GFP fusion proteins for Rbm24b and 42b did not localize into germ plasm as specifically as Hermes or Xvelo, BiFC analysis indicated that both interact with Hermes in germ plasm RNPs. They are very stable in the face of RNA depletion, but additive effects of combinations of antisense oligos suggest they may have a role in germ plasm structure and may influence the ability of Hermes protein to effectively enter RNP particles

Compositional Analysis of Lignocellulosic Feedstocks. 2. Method Uncertainties

The most common procedures for characterizing the chemical components of lignocellulosic feedstocks use a two-stage sulfuric acid hydrolysis to fractionate biomass for gravimetric and instrumental analyses. The uncertainty (i.e., dispersion of values from repeated measurement) in the primary data is of general interest to those with technical or financial interests in biomass conversion technology. The composition of a homogenized corn stover feedstock (154 replicate samples in 13 batches, by 7 analysts in 2 laboratories) was measured along with a National Institute of Standards and Technology (NIST) reference sugar cane bagasse, as a control, using this laboratory's suite of laboratory analytical procedures (LAPs). The uncertainty was evaluated by the statistical analysis of these data and is reported as the standard deviation of each component measurement. Censored and uncensored versions of these data sets are reported, as evidence was found for intermittent instrumental and equipment problems. The censored data are believed to represent the “best case” results of these analyses, whereas the uncensored data show how small method changes can strongly affect the uncertainties of these empirical methods. Relative standard deviations (RSD) of 1−3% are reported for glucan, xylan, lignin, extractives, and total component closure with the other minor components showing 4−10% RSD. The standard deviations seen with the corn stover and NIST bagasse materials were similar, which suggests that the uncertainties reported here are due more to the analytical method used than to the specific feedstock type being analyzed

Darkness’s Descent on the American Anthropological Association: A Cautionary Tale

In September 2000, the self-styled “anthropological journalist” Patrick Tierney began to make public his work claiming that the Yanomamö people of South America had been actively—indeed brutally—harmed by the sociobiological anthropologist Napoleon Chagnon and the geneticist-physician James Neel. Following a florid summary of Tierney’s claims by the anthropologists Terence Turner and Leslie Sponsel, the American Anthropological Association (AAA) saw fit to take Tierney’s claims seriously by conducting a major investigation into the matter. This paper focuses on the AAA’s problematic actions in this case but also provides previously unpublished information on Tierney’s falsehoods. The work presented is based on a year of research by a historian of medicine and science. The author intends the work to function as a cautionary tale to scholarly associations, which have the challenging duty of protecting scholarship and scholars from baseless and sensationalistic charges in the era of the Internet and twenty-four-hour news cycles

Multivariate extreme value modelling of sea conditions around the coast of England

It is widely recognised that coastal flood events can arise from combinations of extreme waves and sea levels. For flood risk analysis and the design of coastal structures it is therefore necessary to assess the joint probability of the occurrence of these variables. Traditional methods have involved the application of joint probability contours, defined in terms of extremes of sea conditions that can, if applied without correction factors, lead to the underestimation of flood risk and under-design of coastal structures. This paper describes the application of a robust multivariate statistical model to analyse extreme offshore waves, wind and sea levels around the coast of England. The approach described here is risk based in that it seeks to define extremes of response variables directly, rather than the joint extremes of sea conditions. The output of the statistical model comprises a Monte Carlo simulation of extreme events. These distributions of extreme events have been transformed from offshore to nearshore using a statistical emulator of a wave transformation model. The resulting nearshore extreme sea condition distributions have the potential to be applied for a range of purposes. The application is demonstrated using two structures located on the south coast of England

Increased serum tumor necrosis factor α levels in patients with lenalidomide-induced hypothyroidism

As the use of lenalidomide expands, the poorly understood phenomenon of lenalidomide-induced thyroid abnormalities will increase. In this study we compared rates of therapy-induced hypothyroidism in 329 patients with DLBCL treated with conventional chemotherapy (DLBCL-c) or conventional chemotherapy plus lenalidomide (DLBCL-len). We measured serum levels of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin-6 (IL-6), interleukin-12 (IL-12), and interleukin-15 (IL-15) before and after treatment. We found a significantly higher rate of therapy-induced hypothyroidism in the DLBCL-len group (25.8% vs 1.3%), and we found a statistically significant increase in serum TNF-α in patients with lenalidomide-induced hypothyroidism

A Highly Conserved Poc1 Protein Characterized in Embryos of the Hydrozoan Clytia hemisphaerica: Localization and Functional Studies

Poc1 (Protein of Centriole 1) proteins are highly conserved WD40 domain-containing centriole components, well characterized in the alga Chlamydomonas, the ciliated protazoan Tetrahymena, the insect Drosophila and in vertebrate cells including Xenopus and zebrafish embryos. Functions and localizations related to the centriole and ciliary axoneme have been demonstrated for Poc1 in a range of species. The vertebrate Poc1 protein has also been reported to show an additional association with mitochondria, including enrichment in the specialized “germ plasm” region of Xenopus oocytes. We have identified and characterized a highly conserved Poc1 protein in the cnidarian Clytia hemisphaerica. Clytia Poc1 mRNA was found to be strongly expressed in eggs and early embryos, showing a punctate perinuclear localization in young oocytes. Fluorescence-tagged Poc1 proteins expressed in developing embryos showed strong localization to centrioles, including basal bodies. Anti-human Poc1 antibodies decorated mitochondria in Clytia, as reported in human cells, but failed to recognise endogenous or fluorescent-tagged Clytia Poc1. Injection of specific morpholino oligonucleotides into Clytia eggs prior to fertilization to repress Poc1 mRNA translation interfered with cell division from the blastula stage, likely corresponding to when neosynthesis normally takes over from maternally supplied protein. Cell cycle lengthening and arrest were observed, phenotypes consistent with an impaired centriolar biogenesis or function. The specificity of the defects could be demonstrated by injection of synthetic Poc1 mRNA, which restored normal development. We conclude that in Clytia embryos, Poc1 has an essentially centriolar localization and function

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table