Neoplasia in Three Aye-Ayes (Daubentonia madagascariensis)

Tumours diagnosed in three aged captive aye-ayes (Daubentonia madagascariensis), held in two different institutions, are described. A cerebral glioblastoma was diagnosed based on histological and immunohistochemical findings in one of the animals following initial presentation with bilateral mydriasis, absent pupillary reflex, head tilt and ataxia. A second animal was humanely destroyed due to impaired locomotion associated with spondylosis and a post-mortem diagnosis of cholangiocarcinoma was made based on histology with further confirmation with immunohistochemical labelling for cytokeratin 7. A third aye-aye suffering from dental disease was diagnosed with an oral squamous cell carcinoma following an excisional biopsy from a non-healing wound in the lip. Due to progression of the neoplasia the animal was humanely destroyed and post-mortem examination revealed the presence on an additional unilateral phaeochromocytoma

PPl 15: The First Brown Dwarf Spectroscopic Binary

PPl 15 is the first object to have been confirmed as a brown dwarf by the lithium test (in 1995), though its inferred mass was very close to the substellar limit. It is a member of the Pleiades open cluster. Its position in a cluster color-magnitude diagram suggested that it might be binary, and preliminary indications that it is a double-lined spectroscopic binary were reported by us in 1997. Here we report on the results of a consecutive week of Keck HIRES observations of this system, which yield its orbit. It has a period of about 5.8 days, and an eccentricity of 0.4+/-0.05. The rotation of the stars is slow for this class of objects. Because the system luminosity is divided between 2 objects with a mass ratio of 0.85, this renders each of them an incontrovertible brown dwarf, with masses between 60-70 jupiters. We show that component B is a little redder than A by studying their wavelength-dependent line ratios, and that this variation is compatible with the mass ratio. We confirm that the system has lithium, but cannot support the original conclusion that it is depleted (which would be surprising, given the new masses). This is a system of very close objects which, if they had combined, would have produced a low mass star. We discuss the implications of this discovery for the theories of binary formation and formation of very low mass objects.Comment: Latex, 18 pages, 4 figures, submitted to Astron.

Expression of hypoxia-inducible factor 1α in thyroid carcinomas

Hypoxia-inducible factor 1α (HIF-1α) is upregulated by hypoxia and oncogenic signalling in many solid tumours. Its regulation and function in thyroid carcinomas are unknown. We evaluated the regulation of HIF-1α and target gene expression in primary thyroid carcinomas and thyroid carcinoma cell lines (BcPAP, WRO, FTC-133 and 8505c). HIF-1α was not detectable in normal tissue but was expressed in thyroid carcinomas. Dedifferentiated anaplastic tumours (ATCs) exhibited high levels of nuclear HIF-1α staining. The HIF-1 target glucose transporter 1 was expressed to a similar level in all tumour types, whereas carbonic anhydrase-9 was significantly elevated in ATCs. In vitro studies revealed a functionally active HIF-1α pathway in thyroid cells with transcriptional activation observed after graded hypoxia (1% O2, anoxia) or treatment with a hypoxia mimetic cobalt chloride. High basal and hypoxia-induced expression of HIF-1α in FTC-133 cells that harbour a phosphatase and tensin homologue (PTEN) mutation was reduced by introduction of wild-type PTEN. Similarly, pharmacological inhibition of the phosphoinositide 3-kinase (PI3K) pathway using LY294002 inhibited HIF-1α and HIF-1α targets in all cell lines, including those with B-RAF mutations (BcPAP and 8505c). In contrast, the effects of inhibition of the RAF/MEK/extracellular signal-regulated kinase pathway were restricted by environmental condition and B-RAF mutation status. HIF-1 is functionally expressed in thyroid carcinomas and is regulated not only by hypoxia but also via growth factor signalling pathways and, in particular, the PI3K pathway. Given the strong association of HIF-1α with an aggressive disease phenotype and therapeutic resistance, this pathway may be an attractive target for improved therapy in thyroid carcinomas

The Schr\"oder functional equation and its relation to the invariant measures of chaotic maps

The aim of this paper is to show that the invariant measure for a class of one dimensional chaotic maps, $T(x)$, is an extended solution of the Schr\"oder functional equation, $q(T(x))=\lambda q(x)$, induced by them. Hence, we give an unified treatment of a collection of exactly solved examples worked out in the current literature. In particular, we show that these examples belongs to a class of functions introduced by Mira, (see text). Moreover, as a new example, we compute the invariant densities for a class of rational maps having the Weierstrass $\wp$ functions as an invariant one. Also, we study the relation between that equation and the well known Frobenius-Perron and Koopman's operators.Comment: 9 page

Hsp90 governs dispersion and drug resistance of fungal biofilms

Fungal biofilms are a major cause of human mortality and are recalcitrant to most treatments due to intrinsic drug resistance. These complex communities of multiple cell types form on indwelling medical devices and their eradication often requires surgical removal of infected devices. Here we implicate the molecular chaperone Hsp90 as a key regulator of biofilm dispersion and drug resistance. We previously established that in the leading human fungal pathogen, Candida albicans, Hsp90 enables the emergence and maintenance of drug resistance in planktonic conditions by stabilizing the protein phosphatase calcineurin and MAPK Mkc1. Hsp90 also regulates temperature-dependent C. albicans morphogenesis through repression of cAMP-PKA signalling. Here we demonstrate that genetic depletion of Hsp90 reduced C. albicans biofilm growth and maturation in vitro and impaired dispersal of biofilm cells. Further, compromising Hsp90 function in vitro abrogated resistance of C. albicans biofilms to the most widely deployed class of antifungal drugs, the azoles. Depletion of Hsp90 led to reduction of calcineurin and Mkc1 in planktonic but not biofilm conditions, suggesting that Hsp90 regulates drug resistance through different mechanisms in these distinct cellular states. Reduction of Hsp90 levels led to a marked decrease in matrix glucan levels, providing a compelling mechanism through which Hsp90 might regulate biofilm azole resistance. Impairment of Hsp90 function genetically or pharmacologically transformed fluconazole from ineffectual to highly effective in eradicating biofilms in a rat venous catheter infection model. Finally, inhibition of Hsp90 reduced resistance of biofilms of the most lethal mould, Aspergillus fumigatus, to the newest class of antifungals to reach the clinic, the echinocandins. Thus, we establish a novel mechanism regulating biofilm drug resistance and dispersion and that targeting Hsp90 provides a much-needed strategy for improving clinical outcome in the treatment of biofilm infections