Neuronal characteristics of small-cell lung cancer

Wide ranging experimental evidence suggests that human small-cell lung cancer (SCLC) has a number of molecular and subcellular characteristics normally associated with neurones. This review outlines and discusses these characteristics in the light of recent developments in the field. Emphasis is placed upon neuronal cell adhesion molecules, neurone-restrictive silencer factor, neurotransmitters/peptides and voltage-gated ion, especially Na+ channels. The hypothesis is put forward that acquisition of such characteristics and the membrane ‘excitability' that would follow can accelerate metastatic progression. The clinical potential of the neuronal characteristics of SCLC, in particular ion channel expression/activity, is discussed in relation to possible novel diagnostic and therapeutic modalities

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Electron trapping around a magnetic null

Magnetic reconnection is an important process in astrophysical, space and laboratory plasmas. The magnetic null pair structure is theoretically suggested to be a crucial feature of the three-dimensional magnetic reconnection. The physics around the null pair, however, has not been explored in combination with the magnetic field configuration deduced from in situ observations. Here, we report the identification of the configuration around a null pair and simultaneous electron dynamics near one null of the pair, observed by four Cluster spacecraft in the geo-magnetotail. Further, we propose a new scenario of electron dynamics in the null region, suggesting that electrons are temporarily trapped in the central reconnection region including electron diffusion region resulting in an electron density peak, accelerated possibly by parallel electric field and electron pressure gradient, and reflected from the magnetic cusp mirrors leading to the bi-directional energetic electron beams, which excite the observed high frequency electrostatic waves

Linking Proteomic and Transcriptional Data through the Interactome and Epigenome Reveals a Map of Oncogene-induced Signaling

Cellular signal transduction generally involves cascades of post-translational protein modifications that rapidly catalyze changes in protein-DNA interactions and gene expression. High-throughput measurements are improving our ability to study each of these stages individually, but do not capture the connections between them. Here we present an approach for building a network of physical links among these data that can be used to prioritize targets for pharmacological intervention. Our method recovers the critical missing links between proteomic and transcriptional data by relating changes in chromatin accessibility to changes in expression and then uses these links to connect proteomic and transcriptome data. We applied our approach to integrate epigenomic, phosphoproteomic and transcriptome changes induced by the variant III mutation of the epidermal growth factor receptor (EGFRvIII) in a cell line model of glioblastoma multiforme (GBM). To test the relevance of the network, we used small molecules to target highly connected nodes implicated by the network model that were not detected by the experimental data in isolation and we found that a large fraction of these agents alter cell viability. Among these are two compounds, ICG-001, targeting CREB binding protein (CREBBP), and PKF118–310, targeting β-catenin (CTNNB1), which have not been tested previously for effectiveness against GBM. At the level of transcriptional regulation, we used chromatin immunoprecipitation sequencing (ChIP-Seq) to experimentally determine the genome-wide binding locations of p300, a transcriptional co-regulator highly connected in the network. Analysis of p300 target genes suggested its role in tumorigenesis. We propose that this general method, in which experimental measurements are used as constraints for building regulatory networks from the interactome while taking into account noise and missing data, should be applicable to a wide range of high-throughput datasets.National Science Foundation (U.S.) (DB1-0821391)National Institutes of Health (U.S.) (Grant U54-CA112967)National Institutes of Health (U.S.) (Grant R01-GM089903)National Institutes of Health (U.S.) (P30-ES002109