Genome-wide gene expression profiling suggests distinct radiation susceptibilities in sporadic and post-Chernobyl papillary thyroid cancers

Papillary thyroid cancers (PTCs) incidence dramatically increased in the vicinity of Chernobyl. The cancer-initiating role of radiation elsewhere is debated. Therefore, we searched for a signature distinguishing radio-induced from sporadic cancers. Using microarrays, we compared the expression profiles of PTCs from the Chernobyl Tissue Bank (CTB, n=12) and from French patients with no history of exposure to ionising radiations (n=14). We also compared the transcriptional responses of human lymphocytes to the presumed aetiological agents initiating these tumours, γ-radiation and H2O2. On a global scale, the transcriptomes of CTB and French tumours are indistinguishable, and the transcriptional responses to γ-radiation and H2O2 are similar. On a finer scale, a 118 genes signature discriminated the γ-radiation and H2O2 responses. This signature could be used to classify the tumours as CTB or French with an error of 15–27%. Similar results were obtained with an independent signature of 13 genes involved in homologous recombination. Although sporadic and radio-induced PTCs represent the same disease, they are distinguishable with molecular signatures reflecting specific responses to γ-radiation and H2O2. These signatures in PTCs could reflect the susceptibility profiles of the patients, suggesting the feasibility of a radiation susceptibility test

Increasing the Number of Thyroid Lesions Classes in Microarray Analysis Improves the Relevance of Diagnostic Markers

BackgroundGenetic markers for thyroid cancers identified by microarray analysis have offered limited predictive accuracy so far because of the few classes of thyroid lesions usually taken into account. To improve diagnostic relevance, we have simultaneously analyzed microarray data from six public datasets covering a total of 347 thyroid tissue samples representing 12 histological classes of follicular lesions and normal thyroid tissue. Our own dataset, containing about half the thyroid tissue samples, included all categories of thyroid lesions. Methodology/Principal Findings Classifier predictions were strongly affected by similarities between classes and by the number of classes in the training sets. In each dataset, sample prediction was improved by separating the samples into three groups according to class similarities. The cross-validation of differential genes revealed four clusters with functional enrichments. The analysis of six of these genes (APOD, APOE, CLGN, CRABP1, SDHA and TIMP1) in 49 new samples showed consistent gene and protein profiles with the class similarities observed. Focusing on four subclasses of follicular tumor, we explored the diagnostic potential of 12 selected markers (CASP10, CDH16, CLGN, CRABP1, HMGB2, ALPL2, ADAMTS2, CABIN1, ALDH1A3, USP13, NR2F2, KRTHB5) by real-time quantitative RT-PCR on 32 other new samples. The gene expression profiles of follicular tumors were examined with reference to the mutational status of the Pax8-PPARγ, TSHR, GNAS and NRAS genes. Conclusion/Significance We show that diagnostic tools defined on the basis of microarray data are more relevant when a large number of samples and tissue classes are used. Taking into account the relationships between the thyroid tumor pathologies, together with the main biological functions and pathways involved, improved the diagnostic accuracy of the samples. Our approach was particularly relevant for the classification of microfollicular adenomas

Role of trans-Planckian modes in cosmology

Motivated by the old trans-Planckian (TP) problem of inflationary cosmology, it has been conjectured that any consistent effective field theory should keep TP modes `hidden' behind the Hubble horizon, so as to prevent them from turning classical and thereby affecting macroscopic observations. In this paper we present two arguments against the Hubble horizon being a scale of singular significance as has been put forward in the TP Censorship Conjecture (TCC). First, refinements of TCC are presented that allow for the TP modes to grow beyond the horizon while still keeping the de-Sitter conjecture valid. Second, we show that TP modes can turn classical even well within the Hubble horizon, which, as such, negates this rationale behind keeping them from crossing it. The role of TP modes is known to be less of a problem in warm inflation, because fluctuations start out usually as classical. This allows warm inflation to be more resilient to the TP problem compared to cold inflation. To understand how robust this is, we identity limits where quantum modes can affect the primordial power spectrum in one specific case.Comment: 33 pages, comments welcome; v2: References updated, matches published versio

Le dysfonctionnement thyroïdien : interrelations génétique - environnement

peer reviewe

L'hypothyroïdie subclinique

SCOPUS: re.jinfo:eu-repo/semantics/publishe

Hypercalcaemia after surgical treatment of Cushing's disease.

SCOPUS: le.jinfo:eu-repo/semantics/publishe

Formation mechanism of sPEEK hydrophilized PES supports for forward osmosis

International audiencePolyethersulfone/sulfonated polyetheretherketone (PES/sPEEK) supported osmotic thin film composite (TFC) membranes were fabricated with a focus on the optimization of the support layer of the TFC membrane by the phase inversion process. The polymer solution was cast directly on a glass substrate without any backing fabric to prepare the support layer. All resultant supports showed a fingerlike pore structure. The addition of a more hydrophilic polymer (sPEEK) to the polymer solution induced pores in the bottom layer of the support with average pore diameters ranging from 0.07 to 0.30 μm, which improved water flux. Bottom surface porosities were simply controlled by adjusting the polymer blend ratios. FO experiments were carried out in a high-throughput (HT) crossflow FO cell with DI water and a 0.5 M NaCl solution as feed and draw solution, respectively. TFC membranes with 5% sPEEK showed a water flux in PRO mode of 14.3 LMH and in FO mode of 6.2 LMH, which is superior to the commercial cellulose triacetate (CTA) and TFC membranes (HTI). In addition, a mechanism for the bottom layer formation was proposed. © 201