Predicting clinical outcomes in neuroblastoma with genomic data integration

Background: Neuroblastoma is a heterogeneous disease with diverse clinical outcomes. Current risk group models require improvement as patients within the same risk group can still show variable prognosis. Recently collected genome-wide datasets provide opportunities to infer neuroblastoma subtypes in a more unified way. Within this context, data integration is critical as different molecular characteristics can contain complementary signals. To this end, we utilized the genomic datasets available for the SEQC cohort patients to develop supervised and unsupervised models that can predict disease prognosis. Results: Our supervised model trained on the SEQC cohort can accurately predict overall survival and event-free survival profiles of patients in two independent cohorts. We also performed extensive experiments to assess the prediction accuracy of high risk patients and patients without MYCN amplification. Our results from this part suggest that clinical endpoints can be predicted accurately across multiple cohorts. To explore the data in an unsupervised manner, we used an integrative clustering strategy named multi-view kernel k-means (MVKKM) that can effectively integrate multiple high-dimensional datasets with varying weights. We observed that integrating different gene expression datasets results in a better patient stratification compared to using these datasets individually. Also, our identified subgroups provide a better Cox regression model fit compared to the existing risk group definitions. Conclusion: Altogether, our results indicate that integration of multiple genomic characterizations enables the discovery of subtypes that improve over existing definitions of risk groups. Effective prediction of survival times will have a direct impact on choosing the right therapies for patients.No sponso

A translational repression complex in developing mammalian neural stem cells that regulates neuronal specification

The mechanisms instructing genesis of neuronal sub-types from mammalian neural precursors are not well understood. To address this issue, we have characterized the transcriptional landscape of radial glial precursors (RPs) in the embryonic murine cortex. We show that individual RPs express mRNA, but not protein , for transcriptional specifiers of both deep and superficial layer cortical neurons. Some of these mRNAs, including the superficial versus deep layer neuron transcriptional regulators Brn1 and Tle4, are translationally repressed by their association with the RNA-binding protein Pumilio2 (Pum2) and the 4E-T protein. Disruption of these repressive complexes in RPs mid-neurogenesis by knocking down 4E-T or Pum2 causes aberrant co-expression of deep layer neuron specification proteins in newborn superficial layer neurons. Thus, cortical RPs are transcriptionally primed to generate diverse types of neurons, and a Pum2/4E-T complex represses translation of some of these neuronal identity mRNAs to ensure appropriate temporal specification of daughter neurons.No sponso

Modelling the transient processes produced under heavy particle irradiation

A new model for the thermal spike produced by the nuclear energy loss, as source of transient processes, is derived analytically, for power law dependences of the diffusivity on temperature, as solution of the heat equation. The contribution of the ionizing energy loss to the spike is not included. The range of validity of the model is analysed, and the results are compared with numerical solutions obtained in the frame of the previous model of the authors, which takes into account both nuclear and ionization energy losses, as well as the coupling between the two subsystems in crystalline semiconductors. Particular solutions are discussed and the errors induced by these approximations are analysed.Comment: 13 page

Composição das sementes e dos óleos de semente de tabacos brasileiros

Tobacco seeds of Nicotiana tabacum L. and Nicotiana rustica L. Species were studied regarding protein and oil contents. Fatty acid composition of tobacco seed oils was determined, through as chromatography. The percentage of linoleic acid, the main fatty component, was found to lie between 65.0 and 74.3. It is reported, for the first time, the occurrence of erucic acid, in a percentage higher than trace, but only for two samples. Only with respect to the colour it was observed a difference between oils from the two species.Sementes de tabaco das espécies Nicotiana tabacum L. e Nicotiana rustica L. foram estudadas, comprovando-se seu alto teor oleaginoso. A composição dos óleos de tabaco em ácidos graxos foi examinada por cromatografia de gás, encontrando-se teores de 65,0 a 74,3% para o ácido linoléico, principal componente graxo. Relata-se, pela primeira vez, a ocorrência do ácido erúcico em quantidade maior que traços, embora apenas para duas amostras. Somente quanto à cor foi notada a diferença sensível entre os óleos das duas espécies estudadas

Atmospheric transport and chemistry of trace gases in LMDz5B: evaluation and implications for inverse modelling

Representation of atmospheric transport is a major source of error in the estimation of greenhouse gas sources and sinks by inverse modelling. Here we assess the impact on trace gas mole fractions of the new physical parameterizations recently implemented in the atmospheric global climate model LMDz to improve vertical diffusion, mesoscale mixing by thermal plumes in the planetary boundary layer (PBL), and deep convection in the troposphere. At the same time, the horizontal and vertical resolution of the model used in the inverse system has been increased. The aim of this paper is to evaluate the impact of these developments on the representation of trace gas transport and chemistry, and to anticipate the implications for inversions of greenhouse gas emissions using such an updated model. Comparison of a one-dimensional version of LMDz with large eddy simulations shows that the thermal scheme simulates shallow convective tracer transport in the PBL over land very efficiently, and much better than previous versions of the model. This result is confirmed in three-dimensional simulations, by a much improved reproduction of the radon-222 diurnal cycle. However, the enhanced dynamics of tracer concentrations induces a stronger sensitivity of the new LMDz configuration to external meteorological forcings. At larger scales, the inter-hemispheric exchange is slightly slower when using the new version of the model, bringing them closer to observations. The increase in the vertical resolution (from 19 to 39 layers) significantly improves the representation of stratosphere/troposphere exchange. Furthermore, changes in atmospheric thermodynamic variables, such as temperature, due to changes in the PBL mixing modify chemical reaction rates, which perturb chemical equilibriums of reactive trace gases. One implication of LMDz model developments for future inversions of greenhouse gas emissions is the ability of the updated system to assimilate a larger amount of high-frequency data sampled at high-variability stations. Others implications are discussed at the end of the paper

Natural history of Arabidopsis thaliana and oomycete symbioses

Molecular ecology of plant–microbe interactions has immediate significance for filling a gap in knowledge between the laboratory discipline of molecular biology and the largely theoretical discipline of evolutionary ecology. Somewhere in between lies conservation biology, aimed at protection of habitats and the diversity of species housed within them. A seemingly insignificant wildflower called Arabidopsis thaliana has an important contribution to make in this endeavour. It has already transformed botanical research with deepening understanding of molecular processes within the species and across the Plant Kingdom; and has begun to revolutionize plant breeding by providing an invaluable catalogue of gene sequences that can be used to design the most precise molecular markers attainable for marker-assisted selection of valued traits. This review describes how A. thaliana and two of its natural biotrophic parasites could be seminal as a model for exploring the biogeography and molecular ecology of plant–microbe interactions, and specifically, for testing hypotheses proposed from the geographic mosaic theory of co-evolution

Phylogenetic Study of Plant Q-type C2H2 Zinc Finger Proteins and Expression Analysis of Poplar Genes in Response to Osmotic, Cold and Mechanical Stresses

Plant Q-type C2H2 zinc finger transcription factors play an important role in plant tolerance to various environmental stresses such as drought, cold, osmotic stress, wounding and mechanical loading. To carry out an improved analysis of the specific role of each member of this subfamily in response to mechanical loading in poplar, we identified 16 two-fingered Q-type C2H2-predicted proteins from the poplar Phytozome database and compared their phylogenetic relationships with 152 two-fingered Q-type C2H2 protein sequences belonging to more than 50 species isolated from the NR protein database of NCBI. Phylogenetic analyses of these Q-type C2H2 proteins sequences classified them into two groups G1 and G2, and conserved motif distributions of interest were established. These two groups differed essentially in their signatures at the C-terminus of their two QALGGH DNA-binding domains. Two additional conserved motifs, MALEAL and LVDCHY, were found only in sequences from Group G1 or from Group G2, respectively. Functional significance of these phylogenetic divergences was assessed by studying transcript accumulation of six poplar C2H2 Q-type genes in responses to abiotic stresses; but no group specificity was found in any organ. Further expression analyses focused on PtaZFP1 and PtaZFP2, the two genes strongly induced by mechanical loading in poplars. The results revealed that these two genes were regulated by several signalling molecules including hydrogen peroxide and the phytohormone jasmonate

FMR investigations of half-metallic ferromagnets

Thin films of various half-metallic ferromagnets, such as chromium dioxide (CrO 2) and Heusler alloys (Co 2Cr 0.6Fe 0.4Al, Co 2MnSi) have been investigated by ferromagnetic resonance (FMR) technique. It is demonstrated that FMR is a very efficient method to study the nanoscale magnetic properties, in particular to probe the magnetic anisotropy and magnetic inhomogeneities of ferromagnetic thin films. Epitaxial CrO 2 thin films of various thicknesses (25-535 nm) have been deposited on TiO 2(100) substrates by chemical vapor deposition process. It is shown that the magnetic behavior of the CrO 2 films results from a competition between the magnetocrystalline and strain anisotropies. For the ultrathin CrO 2 film (25 nm) the magnetic easy axis switches from the c-direction to the b-direction of the rutile structure. Thin-film Co 2Cr 0.6Fe 0.4Al samples (25 nm or 100 nm) have been grown by DC magnetron sputtering either on unbuffered SiO 2(100) substrates or on the substrates capped by a 50 nm thick V buffer layer. The effects of the vanadium buffer layer and of the film thickness are revealed by FMR studies of the Co 2Cr 0.6Fe 0.4Al samples. Well-resolved multiple spin-wave modes are observed in the unbuffered Co 2Cr 0.6Fe 0.4Al sample with a thickness of 100 nm and the exchange stiffness constant has been estimated. Thin films of Co 2MnSi (4-100 nm) have been grown by DC sputtering on silicon substrates on top of a 42 nm thick V seed layer and capped either by Al 2O 3 or by Co and V layers. A set of the 80 nm thick films has been annealed at different temperatures in the range of 425-550°C. FMR studies of the Co 2MnSi samples shows that at the fixed annealing temperature (450°C) the highest magnetization is observed in the sample with a thickness of 61 nm, while the thicker samples (100 nm) reveal not only a lower magnetization but greater magnetic inhomogeneity as well. An annealing treatment at T ≥ 450°C is essential to obtain higher magnetization as well as uniform magnetic properties in the Co 2MnSi films. Weak SWR modes have also been observed in the thick Heusler films. © 2006 WILEY-VCH Verlag GmbH & Co. KGaA