Understanding the molecular mechanisms that promote successful tissue regeneration is critical for continued advancements in regenerative medicine. Vertebrate amphibian tadpoles of the species Xenopus laevis and Xenopus tropicalis have remarkable abilities to regenerate their tails following amputation 1, 2, via the coordinated activity of numerous growth factor signaling pathways, including the Wnt, Fgf, BMP, notch, and TGFβ pathways 3-6. Little is known, however, about the events that act upstream of these signalling pathways following injury. Here, we show that Xenopus tadpole tail amputation induces a sustained production of reactive oxygen species (ROS) during tail regeneration. Lowering ROS levels, via pharmacological or genetic approaches, reduces cell proliferation and impairs tail regeneration. Genetic rescue experiments restored both ROS production and the initiation of the regenerative response. Sustained increased ROS levels are required for Wnt/β-catenin signaling and the activation of one of its major downstream targets, fgf20 7, which, in turn, is essential for proper tail regeneration. These findings demonstrate that injury-induced ROS production is an important regulator of tissue regeneration.

Gliomas are the most frequent primary brain tumours in adults with over 9,000 people diagnosed each year in the UK. A rapid, reagent-free and cost-effective diagnostic regime using serum spectroscopy would allow for rapid diagnostic results and for swift treatment planning and monitoring within the clinical environment. We report the use of ATR-FTIR spectral data combined with a RBF-SVM for the diagnosis of gliomas (high-grade and low-grade) from non-cancer with sensitivities and specificities on average of 93.75 and 96.53% respectively. The proposed diagnostic regime has the ability to reduce mortality and morbidity rates.

The ability to diagnose cancer rapidly with high sensitivity and specificity is essential to exploit advances in new treatments to lead significant reductions in mortality and morbidity. Current cancer diagnostic tests observing tissue architecture and specific protein expression for specific cancers suffer from inter-observer variability, poor detection rates and occur when the patient is symptomatic. A new method for the detection of cancer using 1 μl of human serum, attenuated total reflection—Fourier transform infrared spectroscopy and pattern recognition algorithms is reported using a 433 patient dataset (3897 spectra). To the best of our knowledge, we present the largest study on serum mid-infrared spectroscopy for cancer research. We achieve optimum sensitivities and specificities using a Radial Basis Function Support Vector Machine of between 80.0 and 100 % for all strata and identify the major spectral features, hence biochemical components, responsible for the discrimination within each stratum. We assess feature fed-SVM analysis for our cancer versus non-cancer model and achieve 91.5 and 83.0 % sensitivity and specificity respectively. We demonstrate the use of infrared light to provide a spectral signature from human serum to detect, for the first time, cancer versus non-cancer, metastatic cancer versus organ confined, brain cancer severity and the organ of origin of metastatic disease from the same sample enabling stratified diagnostics depending upon the clinical question asked.Electronic supplementary materialThe online version of this article (doi:10.1007/s11060-016-2060-x) contains supplementary material, which is available to authorized users.

The larval epidermis of Xenopus is a bilayered epithelium, which is an excellent model system for the study of the development and function of mucosal and mucociliary epithelia. Goblet cells develop in the outer layer while multiciliated cells and ionocytes sequentially intercalate from the inner to the outer layer. Here, we identify and characterise a fourth cell type, the small secretory cell (SSC). We show that the development of these cells is controlled by the transcription factor Foxa1 and that they intercalate into the outer layer of the epidermis relatively late, at the same time as embryonic hatching. Ultrastructural and molecular characterisation shows that these cells have an abundance of large apical secretory vesicles, which contain highly glycosylated material, positive for binding of the lectin, peanut agglutinin, and an antibody to the carbohydrate epitope, HNK-1. By specifically depleting SSCs, we show that these cells are crucial for protecting the embryo against bacterial infection. Mass spectrometry studies show that SSCs secrete a glycoprotein similar to Otogelin, which may form the structural component of a mucus-like protective layer, over the surface of the embryo, and several potential antimicrobial substances. Our study completes the characterisation of all the epidermal cell types in the early tadpole epidermis and reinforces the suitability of this system for the in vivo study of complex epithelia, including investigation of innate immune defences.

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The interactions between broody behaviour and changes in concentrations of plasma prolactin and LH were investigated in bantam hens. Adoption of newly hatched chicks caused incubating hens to leave their nests and prevented plasma prolactin decreasing as rapidly as in hens deprived of their nests and not given chicks. Further, the hens allowed to rear chicks came back into lay later (P less than 0.001) than the hens not allowed chicks. Plasma prolactin decreased and plasma LH increased in hens deprived of their nests: these changes were reversed when the hens re-nested. The changes in plasma LH and prolactin in nest-deprived and re-nesting birds were not always synchronous; this was particularly clear immediately after nest deprivation when the increase in plasma LH preceded the decrease in the plasma prolactin. Readiness to incubate disappeared between 48 and 72 h after nest deprivation and corresponded with the time when plasma prolactin decreased to baseline values. Administration of ovine prolactin depressed (P less than 0.01) the initial increase in plasma LH after nest deprivation, but repeated administration of prolactin for up to 72 h failed to suppress plasma LH to the values found in incubating hens. Repeated administration of ovine prolactin at 5- to 8-h intervals for 72 h maintained readiness to incubate in nest-deprived hens. It is concluded that the secretion of prolactin in broody hens is facilitated by the presence of chicks and that increased concentrations of plasma prolactin maintain incubation behaviour. In incubating hens the secretion of LH and prolactin may be partly regulated independently. In addition, LH secretion may also be inhibited by increased plasma prolactin.

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BackgroundThe molecular mechanisms governing vertebrate appendage regeneration remain poorly understood. Uncovering these mechanisms may lead to novel therapies aimed at alleviating human disfigurement and visible loss of function following injury. Here, we explore tadpole tail regeneration in Xenopus tropicalis, a diploid frog with a sequenced genome.ResultsWe found that, like the traditionally used Xenopus laevis, the Xenopus tropicalis tadpole has the capacity to regenerate its tail following amputation, including its spinal cord, muscle, and major blood vessels. We examined gene expression using the Xenopus tropicalis Affymetrix genome array during three phases of regeneration, uncovering more than 1,000 genes that are significantly modulated during tail regeneration. Target validation, using RT-qPCR followed by gene ontology (GO) analysis, revealed a dynamic regulation of genes involved in the inflammatory response, intracellular metabolism, and energy regulation. Meta-analyses of the array data and validation by RT-qPCR and in situ hybridization uncovered a subset of genes upregulated during the early and intermediate phases of regeneration that are involved in the generation of NADP/H, suggesting that these pathways may be important for proper tail regeneration.ConclusionsThe Xenopus tropicalis tadpole is a powerful model to elucidate the genetic mechanisms of vertebrate appendage regeneration. We have produced a novel and substantial microarray data set examining gene expression during vertebrate appendage regeneration.