Combining Classical and Molecular Approaches Elaborates on the Complexity of Mechanisms Underpinning Anterior Regeneration

The current model of planarian anterior regeneration evokes the establishment of low levels of Wnt signalling at anterior wounds, promoting anterior polarity and subsequent elaboration of anterior fate through the action of the TALE class homeodomain PREP. The classical observation that decapitations positioned anteriorly will regenerate heads more rapidly than posteriorly positioned decapitations was among the first to lead to the proposal of gradients along an anteroposterior (AP) axis in a developmental context. An explicit understanding of this phenomenon is not included in the current model of anterior regeneration. This raises the question what the underlying molecular and cellular basis of this temporal gradient is, whether it can be explained by current models and whether understanding the gradient will shed light on regenerative events. Differences in anterior regeneration rate are established very early after amputation and this gradient is dependent on the activity of Hedgehog (Hh) signalling. Animals induced to produce two tails by either Smed-APC-1(RNAi) or Smed-ptc(RNAi) lose anterior fate but form previously described ectopic anterior brain structures. Later these animals form peri-pharyngeal brain structures, which in Smed-ptc(RNAi) grow out of the body establishing a new A/P axis. Combining double amputation and hydroxyurea treatment with RNAi experiments indicates that early ectopic brain structures are formed by uncommitted stem cells that have progressed through S-phase of the cell cycle at the time of amputation. Our results elaborate on the current simplistic model of both AP axis and brain regeneration. We find evidence of a gradient of hedgehog signalling that promotes posterior fate and temporarily inhibits anterior regeneration. Our data supports a model for anterior brain regeneration with distinct early and later phases of regeneration. Together these insights start to delineate the interplay between discrete existing, new, and then later homeostatic signals in AP axis regeneration

A nocturnal atmospheric loss of CH2I2 in the remote marine boundary layer.

Ocean emissions of inorganic and organic iodine compounds drive the biogeochemical cycle of iodine and produce reactive ozone-destroying iodine radicals that influence the oxidizing capacity of the atmosphere. Di-iodomethane (CH2I2) and chloro-iodomethane (CH2ICl) are the two most important organic iodine precursors in the marine boundary layer. Ship-borne measurements made during the TORERO (Tropical Ocean tRoposphere Exchange of Reactive halogens and Oxygenated VOC) field campaign in the east tropical Pacific Ocean in January/February 2012 revealed strong diurnal cycles of CH2I2 and CH2ICl in air and of CH2I2 in seawater. Both compounds are known to undergo rapid photolysis during the day, but models assume no night-time atmospheric losses. Surprisingly, the diurnal cycle of CH2I2 was lower in amplitude than that of CH2ICl, despite its faster photolysis rate. We speculate that night-time loss of CH2I2 occurs due to reaction with NO3 radicals. Indirect results from a laboratory study under ambient atmospheric boundary layer conditions indicate a k CH2I2+NO3 of ≤4 × 10-13 cm3 molecule-1 s-1; a previous kinetic study carried out at ≤100 Torr found k CH2I2+NO3 of 4 × 10-13 cm3 molecule-1 s-1. Using the 1-dimensional atmospheric THAMO model driven by sea-air fluxes calculated from the seawater and air measurements (averaging 1.8 +/- 0.8 nmol m-2 d-1 for CH2I2 and 3.7 +/- 0.8 nmol m-2 d-1 for CH2ICl), we show that the model overestimates night-time CH2I2 by >60 % but reaches good agreement with the measurements when the CH2I2 + NO3 reaction is included at 2-4 × 10-13 cm3 molecule-1 s-1. We conclude that the reaction has a significant effect on CH2I2 and helps reconcile observed and modeled concentrations. We recommend further direct measurements of this reaction under atmospheric conditions, including of product branching ratios.LJC acknowledges NERC (NE/J00619X/1) and the National Centre for Atmospheric Science (NCAS) for funding. The laboratory work was supported by the NERC React-SCI (NE/K005448/1) and RONOCO (NE/F005466/1) grants.This is the final version of the article. It was first available from Springer via http://dx.doi.org/10.1007/s10874-015-9320-

HSPG-Deficient Zebrafish Uncovers Dental Aspect of Multiple Osteochondromas

Multiple Osteochondromas (MO; previously known as multiple hereditary exostosis) is an autosomal dominant genetic condition that is characterized by the formation of cartilaginous bone tumours (osteochondromas) at multiple sites in the skeleton, secondary bursa formation and impingement of nerves, tendons and vessels, bone curving, and short stature. MO is also known to be associated with arthritis, general pain, scarring and occasional malignant transformation of osteochondroma into secondary peripheral chondrosarcoma. MO patients present additional complains but the relevance of those in relation to the syndromal background needs validation. Mutations in two enzymes that are required during heparan sulphate synthesis (EXT1 or EXT2) are known to cause MO. Previously, we have used zebrafish which harbour mutations in ext2 as a model for MO and shown that ext2−/− fish have skeletal defects that resemble those seen in osteochondromas. Here we analyse dental defects present in ext2−/− fish. Histological analysis reveals that ext2−/− fish have very severe defects associated with the formation and the morphology of teeth. At 5 days post fertilization 100% of ext2−/− fish have a single tooth at the end of the 5th pharyngeal arch, whereas wild-type fish develop three teeth, located in the middle of the pharyngeal arch. ext2−/− teeth have abnormal morphology (they were shorter and thicker than in the WT) and patchy ossification at the tooth base. Deformities such as split crowns and enamel lesions were found in 20% of ext2+/− adults. The tooth morphology in ext2−/− was partially rescued by FGF8 administered locally (bead implants). Our findings from zebrafish model were validated in a dental survey that was conducted with assistance of the MHE Research Foundation. The presence of the malformed and/or displaced teeth with abnormal enamel was declared by half of the respondents indicating that MO might indeed be also associated with dental problems

A Family History of Lethal Prostate Cancer and Risk of Aggressive Prostate Cancer in Patients Undergoing Radical Prostatectomy

We investigated whether a family history of lethal prostate cancer (PCa) was associated with high-risk disease or biochemical recurrence in patients undergoing radical prostatectomy. A cohort of radical prostatectomy patients was stratified into men with no family history of PCa (NFH); a first-degree relative with PCa (FH); and those with a first-degree relative who had died of PCa (FHD). Demographic, operative and pathologic outcomes were analyzed. Freedom from biochemical recurrence was examined using Kaplan-Meier log rank. A multivariate Cox logistic regression analysis was also performed. We analyzed 471 men who underwent radical prostatectomy at our institution with known family history. The three groups had: 355 patients (75%) in NFH; 97 patients (21%) in FH; and 19 patients (4%) in FHD. The prevalence of a Gleason score ≥8, higher pathologic T stage, and biochemical recurrence (BCR) rates did not significantly differ between groups. On Kaplan-Meier analysis there were no differences in short-term BCR rates (p = 0.212). In this cohort of patients undergoing radical prostatectomy, those with first-degree relatives who died of PCa did not have an increased likelihood of high-risk or aggressive PCa or shorter-term risk of BCR than those who did not