On the Influence of Uncertainties in Chemical Reaction Rates on Results of the Astrochemical Modelling

With the chemical reaction rate database UMIST95 (Millar et al. 1997) we analyze how uncertainties in rate constants of gas-phase chemical reactions influence the modelling of molecular abundances in the interstellar medium. Random variations are introduced into the rate constants to estimate the scatter in theoretical abundances. Calculations are performed for dark and translucent molecular clouds where gas phase chemistry is adequate. Similar approach was used by Pineau des Forets & Roueff (2000) for the study of chemical bistability. All the species are divided into 6 sensitivity groups according to the value of the scatter in their model abundances computed with varied rate constants. It is shown that the distribution of species within these groups depends on the number of atoms in a molecule and on the adopted physical conditions. The simple method is suggested which allows to single out reactions that are most important for the evolution of a given species.Comment: 4 pages. To appear in the proceedings of the 4th Cologne-Bonn Zermatt Symposiu

The influence of cosmic rays in the circumnuclear molecular gas of NGC1068

We surveyed the circumnuclear disk of the Seyfert galaxy NGC1068 between the frequencies 86.2 GHz and 115.6 GHz, and identified 17 different molecules. Using a time and depth dependent chemical model we reproduced the observational results, and show that the column densities of most of the species are better reproduced if the molecular gas is heavily pervaded by a high cosmic ray ionization rate of about 1000 times that of the Milky Way. We discuss how molecules in the NGC1068 nucleus may be influenced by this external radiation, as well as by UV radiation fields.Comment: 6 pages. Conference proceeding for the workshop on "Cosmic-ray induced phenomenology in star-forming environments" held in Sant Cugat, Spain, on April 16-19, 201

Mesenchymal Transition and PDGFRA Amplification/Mutation Are Key Distinct Oncogenic Events in Pediatric Diffuse Intrinsic Pontine Gliomas

Diffuse intrinsic pontine glioma (DIPG) is one of the most frequent malignant pediatric brain tumor and its prognosis is universaly fatal. No significant improvement has been made in last thirty years over the standard treatment with radiotherapy. To address the paucity of understanding of DIPGs, we have carried out integrated molecular profiling of a large series of samples obtained with stereotactic biopsy at diagnosis. While chromosomal imbalances did not distinguish DIPG and supratentorial tumors on CGHarrays, gene expression profiling revealed clear differences between them, with brainstem gliomas resembling midline/thalamic tumours, indicating a closely-related origin. Two distinct subgroups of DIPG were identified. The first subgroup displayed mesenchymal and pro-angiogenic characteristics, with stem cell markers enrichment consistent with the possibility to grow tumor stem cells from these biopsies. The other subgroup displayed oligodendroglial features, and appeared largely driven by PDGFRA, in particular through amplification and/or novel missense mutations in the extracellular domain. Patients in this later group had a significantly worse outcome with an hazard ratio for early deaths, ie before 10 months, 8 fold greater that the ones in the other subgroup (p = 0.041, Cox regression model). The worse outcome of patients with the oligodendroglial type of tumors was confirmed on a series of 55 paraffin-embedded biopsy samples at diagnosis (median OS of 7.73 versus 12.37 months, p = 0.045, log-rank test). Two distinct transcriptional subclasses of DIPG with specific genomic alterations can be defined at diagnosis by oligodendroglial differentiation or mesenchymal transition, respectively. Classifying these tumors by signal transduction pathway activation and by mutation in pathway member genes may be particularily valuable for the development of targeted therapies

Expression of miR-487b and miR-410 encoded by 14q32.31 locus is a prognostic marker in neuroblastoma

BACKGROUND: Combination of age at diagnosis, stage and MYCN amplification stratifies neuroblastoma into low-risk and high-risk. We aimed to establish whether a microRNA (miRNA) signature could be associated with prognosis in both groups. METHODS: Microarray expression profiling of human miRNAs and quantitative reverse-transcriptase PCR of selected miRNAs were performed on a preliminary cohort of 13 patients. Results were validated on an independent cohort of 214 patients. The relationship between miRNA expression and the overall or disease-free survival was analysed on the total cohort of 227 patients using the log-rank test and the multivariable Cox proportional hazard model. RESULTS: A total of 15 of 17 miRNAs that discriminated high-risk from low-risk neuroblastoma belonged to the imprinted human 14q32.31 miRNA cluster and two, miR-487b and miR-410, were significantly downregulated in the high-risk group. Multivariable analyses showed miR-487b expression as associated with overall survival and disease-free survival in the whole cohort, independently of clinical covariates. Moreover, miR-487b and miR-410 expression was significantly associated with disease-free survival of the non-MYCN-amplified favourable neuroblastoma: localised (stage 1, 2 and 3) and stage 4 of infant <18 months. CONCLUSION: Expression of miR-487b and miR-410 shows predictive value beyond the classical high-/low-risk stratification and is a biomarker of relapse in favourable neuroblastoma