MicroRNA expression in HTLV-1 infection and pathogenesis

Our laboratory is examining the profiles of microRNA expression in ATLL cells and infected T-cell lines using microarrays and small RNA libraries. Microarray analysis of ATLL samples revealed 6 upregulated and 21 downregulated microRNAs in ATLL cells compared to CD4+ T-cell controls. Potential targets for deregulated microRNAs were identified by integrating microRNA and mRNA expression profiles. Current experiments are aimed at verifying these predicted microRNA-target interactions

A Boolean Approach to Linear Prediction for Signaling Network Modeling

The task of the DREAM4 (Dialogue for Reverse Engineering Assessments and Methods) “Predictive signaling network modeling” challenge was to develop a method that, from single-stimulus/inhibitor data, reconstructs a cause-effect network to be used to predict the protein activity level in multi-stimulus/inhibitor experimental conditions. The method presented in this paper, one of the best performing in this challenge, consists of 3 steps: 1. Boolean tables are inferred from single-stimulus/inhibitor data to classify whether a particular combination of stimulus and inhibitor is affecting the protein. 2. A cause-effect network is reconstructed starting from these tables. 3. Training data are linearly combined according to rules inferred from the reconstructed network. This method, although simple, permits one to achieve a good performance providing reasonable predictions based on a reconstructed network compatible with knowledge from the literature. It can be potentially used to predict how signaling pathways are affected by different ligands and how this response is altered by diseases

A subcellular model of pancreatic insulin secretion

When glucose is raised from a basal to stimulating level, the pancreatic islets respond with a typical biphasic insulin secretion pattern. Moreover, the pancreas is able to recognize the rate of change of the glucose concentration. We present a relatively simple model of insulin secretion from pancreatic beta-cells, yet founded on solid physiological grounds and capable of reproducing a series of secretion patterns from perfused pancreases as well as from stimulated islets. The model includes the notion of distinct pools of granules as well as mechanisms such as mobilization, priming, exocytosis and kiss-and-run. Based on experimental data, we suggest that the individual beta-cells activate at different glucose concentrations. The model reproduces most of the data it was tested against very well, and can therefore serve as a general model of glucose-stimulated insulin secretion. Simulations predict that the effect of an increased frequency of kiss-and-run exocytotic events is a reduction in insulin secretion without modification of the qualitative pattern. Our model also appears to be the first physiology-based one to reproduce the staircase experiment, which underlies 'derivative control', i.e. the pancreatic capacity of measuring the rate of change of the glucose concentration

Role of microRNAs in HTLV-1 infection and transformation

Human T-cell leukemia virus type 1 (HTLV-1), a retrovirus that infects more than 20 million people worldwide, is the etiological agent of ATLL (adult T-cell leukemia/lymphoma), an aggressive leukemia of CD4+ T lymphocytes which arises in a small percentage of infected individuals after a long clinical latency. Tumor emergence is attributed primarily to the oncogenic activity of the viral protein Tax, which drives the expression of viral transcripts and controls the expression and function of a broad variety of host-cell genes involved in proliferation, genetic stability and apoptosis. Nevertheless, many aspects of HTLV-1 replication, persistence and pathogenesis remain to be understood. The emerging role of microRNAs in tumor development and viral infection has prompted investigations on the interactions between HTLV-1 and the microRNA regulatory network. In the present review we discuss recent data demonstrating changes in cellular microRNA expression in HTLV-1-infected cell lines and ATLL cells, and the functional impact of a subset microRNAs deregulated by HTLV-1 on cellular gene expression and signal transduction pathways. Mechanisms through which the viral proteins may influence microRNA expression are discussed. Results of searches for potential cellular microRNAs that target viral transcripts and for microRNAs produced by HTLV-1 are described. Observations along with regarding the expression of tRNA-derived small regulatory RNAs in HTLV-1-infected cells are presented

Differential Diagnosis of Benign and Malignant Thyroid Nodules at Elastosonography

PURPOSE: Ultrasound of the neck detects a large number of non-palpable thyroid nodules in the population, but it offers poor diagnostic accuracy (the presence of microcalcifications is the only statistically significant criterion indicative of malignancy). The aim of this study is to evaluate elastography, a technique which allows differentiation between pathological and normal tissue by determining its hardness and which could also prove useful in the characterisation of thyroid nodules. MATERIALS AND METHODS: In this prospective study, 51 thyroid nodules in 40 consecutive patients were examined (25 women, 15 men, mean age +/- SD, 54 +/- 13.4). Elastosonography was performed by real-time, free-hand technique, using Logos HiVision equipment with a 10 MHz transducer and lesions were classified and scored in 4 classes of hardness. All patients were also examined by grey scale high frequency ultrasound and colour Doppler. Final diagnoses were obtained from cytological and/or histological evaluation. RESULTS: Final diagnoses revealed 11 malignant and 40 benign nodules. Only in two cases ultrasound demonstrated signs useful for a differential diagnosis (intrinsic microcalcifications). Correct differentiation of malignant from benign nodules was obtained by elastosonography in 43 / 51 cases with 5 false positives (FP) and 3 false negatives (FN). Specificity, sensitivity and accuracy were 87.5 %, 81.8 % and 86.2 %, respectively. Predictive negative value (PNV) and predictive positive value (PPV) were 94.5 % and 64 % area under the curve (AUC) 0.86. CONCLUSION: Elastosonography provides an interesting contribution to the differentiation of malignant and benign thyroid nodules. Particularly worthy of mention is that an entirely elastic nodule pattern was observed only in relation to benign nodules, a result which would suggest that immediate recourse to FNAB might be avoide