Overexpression of sonic hedgehog suppresses embryonic hair follicle morphogenesis

The Sonic Hedgehog (Shh) signalling pathway plays a central role in the development of the skin and hair follicle and is a major determinant of skin tumorigenesis, most notably of basal cell carcinoma (BCC). Various mouse models involving either ablation or overexpression of key members of the Shh signalling pathway display a range of skin tumours. To further examine the role of Shh in skin development. we have overexpressed Shh in a subset of interfollicular basal cells from 12.5 dpc under the control of the human keratin 1 (HK1) promoter. The HK1-Shh transgenic mice display a range of skin anomalies, including highly pigmented inguinal lesions and regions of alopecia. The most striking hair follicle phenotype is a suppression in embryonic follicle development between 14.0 and 19.0 dpc, resulting in a complete absence of guard, awl, and auchene hair fibres. These data indicate that alternative signals are responsible for the development of different hair follicles and point to a major role of Shh signalling in the morphogenesis of guard, awl, and auchene hair fibres. Through a comparison with other mouse models, the characteristics of the HK1-Shh transgenic mice suggest that the precise timing and site of Shh expression are key in dictating the resultant skin and tumour phenotype. 2003 Elsevier Inc. All rights reserved.

Benign intracranial hypertension associated with acromegaly

This is the first reported case of benign intracranial hypertension (BIH) occurring with acromegaly and resolving after successful treatment of a growth hormone-secreting pituitary adenoma. BIH has been reported with recombinant human growth hormone (rhGH) therapy of GH deficient patients and insulin-like growth factor I (IGF-I) treatment of growth hormone (GH) insensitivity (Laron syndrome) in children. We postulate that the proposed mechanism causing BIH in rhGH-treated children and in acromegaly results from increased cerebrospinal fluid production from the choroid plexi secondary to elevated cerebrospinal fluid growth hormone concentrations that trigger local IGF-I secretion and activation of IGF-I receptors.

Interspecific variation in the use of carotenoid-based coloration in birds: diet, life history and phylogeny

Birds show striking interspecific variation in their use of carotenoid-based coloration. Theory predicts that the use of carotenoids for coloration is closely associated with the availability of carotenoids in the diet but, although this prediction has been supported in single-species studies and those using small numbers of closely related species, there have been no broad-scale quantitative tests of the link between carotenoid coloration and diet. Here we test for such a link using modern comparative methods, a database on 140 families of birds and two alternative avian phylogenies. We show that carotenoid pigmentation is more common in the bare parts (legs, bill and skin) than in plumage, and that yellow coloration is more common than red. We also show that there is no simple, general association between the availability of carotenoids in the diet and the overall use of carotenoid-based coloration. However, when we look at plumage coloration separately from bare part coloration, we find there is a robust and significant association between diet and plumage coloration, but not between diet and bare part coloration. Similarly, when we look at yellow and red plumage colours separately, we find that the association between diet and coloration is typically stronger for red coloration than it is for yellow coloration. Finally, when we build multivariate models to explain variation in each type of carotenoid-based coloration we find that a variety of life history and ecological factors are associated with different aspects of coloration, with dietary carotenoids only being a consistent significant factor in the case of variation in plumage. All of these results remain qualitatively unchanged irrespective of the phylogeny used in the analyses, although in some cases the precise life history and ecological variables included in the multivariate models do vary. Taken together, these results indicate that the predicted link between carotenoid coloration and diet is idiosyncratic rather than general, being strongest with respect to plumage colours and weakest for bare part coloration. We therefore suggest that, although the carotenoid-based bird plumage may a good model for diet-mediated signalling, the use of carotenoids in bare part pigmentation may have a very different functional basis and may be more strongly influenced by genetic and physiological mechanisms, which currently remain relatively understudied.

Neogenin interacts with RGMa and Netrin-1 to guide axons within the embryonic vertebrate forebrain

In the embryonic forebrain, pioneer axons establish a simple topography of dorsoventral and longitudinal tracts. The cues used by these axons during the initial formation of the axon scaffold remain largely unknown. We have investigated the axon guidance role of Neogenin, a member of the immunoglobulin (Ig) superfamily that binds to the chemoattractive ligand Netrin-1, as well as to the chemorepulsive ligand repulsive guidance molecule (RGMa). Here, we show strong expression of Neogenin and both of its putative ligands in the developing Xenopus forebrain. Neogenin loss-of-function mutants revealed that this receptor was essential for axon guidance in an early forming dorsoventral brain pathway. Similar mutant phenotypes were also observed following loss of either RGMa or Netrin-1. Simultaneous partial knock downs of these molecules revealed dosage-sensitive interactions and confirmed that these receptors and ligands were acting in the same pathway. The results provide the first evidence that Neogenin acts as an axon guidance molecule in vivo and support a model whereby Neogenin-expressing axons respond to a combination of attractive and repulsive cues as they navigate their ventral trajectory. (c) 2006 Elsevier Inc. All rights reserved.

Data mining and simulation: a grey relationship demonstration

Fuzzy data has grown to be an important factor in data mining. Whenever uncertainty exists, simulation can be used as a model. Simulation is very flexible, although it can involve significant levels of computation. This article discusses fuzzy decision-making using the grey related analysis method. Fuzzy models are expected to better reflect decision-making uncertainty, at some cost in accuracy relative to crisp models. Monte Carlo simulation is used to incorporate experimental levels of uncertainty into the data and to measure the impact of fuzzy decision tree models using categorical data. Results are compared with decision tree models based on crisp continuous data.

Estimating nutrient intake in comparative studies of animals: an example using dietary carotenoid content in birds

Many different methods of reporting animal diets have been used in ecological research. These vary greatly in level of accuracy and precision and therefore complicate attempts to measure and compare diets, and quantitites of nutrients in those diets, across a wide range of taxa. For most birds, the carotenoid content of the diet has not been directly measured. Here, therefore, I use an avian example to show how different methods of measuring the quantities of various foods in the diet affect the relative rankings of higher taxa (families, subfamilies, and tribes), and species within these taxa, with regard to the carotenoid contents of their diets. This is a timely example, as much recent avian literature has focused on the way dietary carotenoids may be traded off among aspects of survival, fitness and signalling. I assessed the mean dietary carotenoid contents of representatives of thirty higher taxa of birds using four different carotenoid intake indices varying in precision, including trophic levels, a coarse-scale and a fine-scale categorical index, and quantitative estimates of dietary carotenoids. This last method was used as the benchmark. For comparisons among taxa, all but the trophic level index were significantly correlated with each other. However, for comparisons of species within taxa, the fine-scale index outperformed the coarse-scale index, which in turn outperformed the trophic level index. In addition, each method has advantages and disadvantages, as well as underlying assumptions that must be considered. Examination and comparison of several possible methods of diet assessment appears to highlight these so that the best possible index is used given available data, and it is recommended that such a step be taken prior to the inclusion of estimated nutrient intake in any statistical analysis. Although applied to avian carotenoids here, this method could readily be applied to other taxa and types of nutrients.