Human papillomavirus is detected in transitional cell carcinoma arising in renal transplant recipients

"This is a non-final version of an article published in final form in Pathology The Journal of the Royal College of Pathologists of Australasia 41 (3) pp.245-247"Aims: We investigated the role of human papillomavirus HPV in the development of transitional cell carcinoma TCC arising in renal transplant recipients. Methods: Genomic DNA was extracted from 10 m paraffin embedded sections of five TCCs arising in five renal transplant recipients using the QIAamp DNA mini kit according to the manufacturer's instructions. β-globin PCR was performed to test DNA adequacy. Samples were tested for the presence of HPV DNA by broad spectrum HPV PCR method using non-biotinylated SPF10 primers SPF1A, SPF1B, SPF1C, SPF1D, SPF2B, SPF2D which amplify a short 65 bp fragment. Positive bands were identified on a 3 gel. Positive samples underwent a second HPV PCR and were amplified using biotinylated SPF10 primer set, which amplifies the same 65 bp region of the L1 open reading frame. INNO-LiPA line probe assay was then performed to genotype the samples which uses a reverse hybridisation principle. Results: Four of five TCCs examined were positive for HPV. The high risk HPV16 was detected in three cases whereas in the fourth case an unclassifiable HPV genotype was present. In all DNA samples, β-globin amplification was successful. Conclusions: Our results indicate that HPV and in particular HPV16 may play an aetiological role in the development of TCC in renal transplant patients.Peer reviewedSubmitted Versio

Hedgehog Signalling in Androgen Independent Prostate Cancer

Objectives: Androgen-deprivation therapy effectively shrinks hormone-naïve prostate cancer, both in the prostate and at sites of distant metastasis. However prolonged androgen deprivation generally results in relapse and androgen-independent tumour growth, which is inevitably fatal. The molecular events that enable prostate cancer cells to proliferate in reduced androgen conditions are poorly understood. Here we investigate the role of Hedgehog signalling in androgen-independent prostate cancer (AIPC). Methods: Activity of the Hedgehog signalling pathway was analysed in cultured prostate cancer cells, and circulating prostate tumour cells were isolated from blood samples of patients with AIPC. Results: AIPC cells were derived through prolonged culture in reduced androgen conditions, modelling hormone therapy in patients, and expressed increased levels of Hedgehog signalling proteins. Exposure of cultured AIPC cells to cyclopamine, which inhibits Hedgehog signalling, resulted in inhibition of cancer cell growth. The expression of the Hedgehog receptor PTCH and the highly prostate cancer-specific gene DD3PCA3 was significantly higher in circulating prostate cancer cells isolated from patients with AIPC compared with samples prepared from normal individuals. There was an association between PTCH and DD3PCA3 expression and the length of androgen-ablation therapy. Conclusions: Our data are consistent with reports implicating overactivity of Hedgehog signalling in prostate cancer and suggest that Hedgehog signalling contributes to the androgen-independent growth of prostate cancer cells. As systemic anti-Hedgehog medicines are developed, the Hedgehog pathway will become a potential new therapeutic target in advanced prostate cancer.Peer reviewedFinal Accepted Versio

Frequency-based neural discrimination in fast periodic visual stimulation

Humans capitalize on statistical cues to discriminate fundamental units of information within complex streams of sensory input. We sought neural evidence for this phenomenon by combining fast periodic visual stimulation (FPVS) and EEG recordings. Skilled readers were exposed to sequences of linguistic items with decreasing familiarity, presented at a fast rate and periodically interleaved with oddballs. Crucially, each sequence comprised stimuli of the same category, and the only distinction between base and oddball items was the frequency of occurrence of individual tokens within a stream. Frequency-domain analyses revealed robust neural responses at the oddball presentation rate in all conditions, reflecting the discrimination between two locally-emerged groups of items purely informed by token frequency. Results provide evidence for a fundamental frequency-tuned mechanism that operates under high temporal constraints and could underpin category bootstrapping. Concurrently, they showcase the potential of FPVS for providing a direct neural measure of implicit statistical learning

Resource recovery from desalination, the case of small islands

This work explores resource recovery coupled to seawater desalination in small islands. As small islands depend on seawater desalination for water access, they make an excellent ground for exploring the trade-offs associated to resource recovery, like potential economic gains, energy use, and environmental impacts. Here, we investigated these tensions in the context of Lampedusa, in Italy. We then developed and evaluated scenarios for the recovery of additional water, Mg, and other resources from brines, to identify if and how resource recovery is an interesting approach for the island vis-`a-vis these tensions. We have found that the potential to increase water production with water recovery from brine is an interesting alternative for small islands, especially when harnessing waste heat. However, while some technologies offer possibilities for recovering additional resources, in places like small islands the potential benefits from additional recovery do not seem to justify the costs to the local system

HPV infection and immunochemical detection of cell-cycle markers in verrucous carcinoma of the penis

Penile verrucous carcinoma is a rare disease and little is known of its aetiology or pathogenesis. In this study we examined cell-cycle proteins expression and correlation with human papillomavirus infection in a series of 15 pure penile verrucous carcinomas from a single centre. Of 148 penile tumours, 15 (10%) were diagnosed as pure verrucous carcinomas. The expression of the cell-cycle-associated proteins p53, p21, RB, p16INK4A and Ki67 were examined by immunohistochemistry. Human papillomavirus infection was determined by polymerase chain reaction to identify a wide range of virus types. The expression of p16INK4A and Ki67 was significantly lower in verrucous carcinoma than in usual type squamous cell carcinoma, whereas the expression of p53, p21 and RB was not significantly different. p53 showed basal expression in contrast to usual type squamous cell carcinoma. Human papillomavirus infection was present in only 3 out of 13 verrucous carcinomas. Unique low-risk, high-risk and mixed viral infections were observed in each of the three cases. In conclusion, lower levels of p16INK4A and Ki67 expressions differentiate penile verrucous carcinoma from usual type squamous cell carcinoma. The low Ki67 index reflects the slow-growing nature of verrucous tumours. The low level of p16INK4A expression and human papillomavirus detection suggests that penile verrucous carcinoma pathogenesis is unrelated to human papillomavirus infection and the oncogenes and tumour suppressor genes classically altered by virus infection.Peer reviewedFinal Accepted Versio

HelexKids:a word frequency database for Greek and Cypriot primary school children

In this article, we introduce HelexKids, an online written-word database for Greek-speaking children in primary education (Grades 1 to 6). The database is organized on a grade-by-grade basis, and on a cumulative basis by combining Grade 1 with Grades 2 to 6. It provides values for Zipf, frequency per million, dispersion, estimated word frequency per million, standard word frequency, contextual diversity, orthographic Levenshtein distance, and lemma frequency. These values are derived from 116 textbooks used in primary education in Greece and Cyprus, producing a total of 68,692 different word types. HelexKids was developed to assist researchers in studying language development, educators in selecting age-appropriate items for teaching, as well as writers and authors of educational books for Greek/Cypriot children. The database is open access and can be searched online at www.helexkids.org

GreekLex 2: a comprehensive lexical database with part-of-speech, syllabic, phonological, and stress information

Databases containing lexical properties on any given orthography are crucial for psycholinguistic research. In the last ten years, a number of lexical databases have been developed for Greek. However, these lack important part-of-speech information. Furthermore, the need for alternative procedures for calculating syllabic measurements and stress information, as well as combination of several metrics to investigate linguistic properties of the Greek language are highlighted. To address these issues, we present a new extensive lexical database of Modern Greek (GreekLex 2) with part-of-speech information for each word and accurate syllabification and orthographic information predictive of stress, as well as several measurements of word similarity and phonetic information. The addition of detailed statistical information about Greek part-of-speech, syllabification, and stress neighbourhood allowed novel analyses of stress distribution within different grammatical categories and syllabic lengths to be carried out. Results showed that the statistical preponderance of stress position on the pre-final syllable that is reported for Greek language is dependent upon grammatical category. Additionally, analyses showed that a proportion higher than 90% of the tokens in the database would be stressed correctly solely by relying on stress neighbourhood information. The database and the scripts for orthographic and phonological syllabification as well as phonetic transcription are available at http://www.psychology.nottingham.ac.uk/greeklex/

Inactivation of class II PI3K-C2 alpha induces leptin resistance, age-dependent insulin resistance and obesity in male mice

AIMS/HYPOTHESIS: While the class I phosphoinositide 3-kinases (PI3Ks) are well-documented positive regulators of metabolism, the involvement of class II PI3K isoforms (PI3K-C2α, -C2β and -C2γ) in metabolic regulation is just emerging. Organismal inactivation of PI3K-C2β increases insulin signalling and sensitivity, whereas PI3K-C2γ inactivation has a negative metabolic impact. In contrast, the role of PI3K-C2α in organismal metabolism remains unexplored. In this study, we investigated whether kinase inactivation of PI3K-C2α affects glucose metabolism in mice. METHODS: We have generated and characterised a mouse line with a constitutive inactivating knock-in (KI) mutation in the kinase domain of the gene encoding PI3K-C2α (Pik3c2a). RESULTS: While homozygosity for kinase-dead PI3K-C2α was embryonic lethal, heterozygous PI3K-C2α KI mice were viable and fertile, with no significant histopathological findings. However, male heterozygous mice showed early onset leptin resistance, with a defect in leptin signalling in the hypothalamus, correlating with a mild, age-dependent obesity, insulin resistance and glucose intolerance. Insulin signalling was unaffected in insulin target tissues of PI3K-C2α KI mice, in contrast to previous reports in which downregulation of PI3K-C2α in cell lines was shown to dampen insulin signalling. Interestingly, no metabolic phenotypes were detected in female PI3K-C2α KI mice at any age. CONCLUSIONS/INTERPRETATION: Our data uncover a sex-dependent role for PI3K-C2α in the modulation of hypothalamic leptin action and systemic glucose homeostasis. ACCESS TO RESEARCH MATERIALS: All reagents are available upon request