Enrichment of Targetable Mutations in the Relapsed Neuroblastoma Genome.

Neuroblastoma is characterized by a relative paucity of recurrent somatic mutations at diagnosis. However, recent studies have shown that the mutational burden increases at relapse, likely as a result of clonal evolution of mutation-carrying cells during primary treatment. To inform the development of personalized therapies, we sought to further define the frequency of potentially actionable mutations in neuroblastoma, both at diagnosis and after chemotherapy.

Single mammalian cells compensate for differences in cellular volume and DNA copy number through independent global transcriptional mechanisms.

Individual mammalian cells exhibit large variability in cellular volume, even with the same absolute DNA content, and so must compensate for differences in DNA concentration in order to maintain constant concentration of gene expression products. Using single-molecule counting and computational image analysis, we show that transcript abundance correlates with cellular volume at the single-cell level due to increased global transcription in larger cells. Cell fusion experiments establish that increased cellular content itself can directly increase transcription.

Localization and abundance analysis of human lncRNAs at single-cell and single-molecule resolution.

Background: Long non-coding RNAs (lncRNAs) have been implicated in diverse biological processes. In contrast to extensive genomic annotation of lncRNA transcripts, far fewer have been characterized for subcellular localization and cell-to-cell variability. Addressing this requires systematic, direct visualization of lncRNAs in single cells at single-molecule resolution.

Neural and genetic degeneracy underlies Caenorhabditis elegans feeding behavior.

Degenerate networks, in which structurally distinct elements can perform the same function or yield the same output, are ubiquitous in biology. Degeneracy contributes to the robustness and adaptability of networks in varied environmental and evolutionary contexts. However, how degenerate neural networks regulate behavior in vivo is poorly understood, especially at the genetic level.

Using variability in gene expression as a tool for studying gene regulation.

With the advent of quantitative tools for measuring gene expression in single cells, researchers have made the discovery that in many contexts, messenger RNA and protein levels can vary widely from cell to cell, often because of inherently stochastic events associated with gene expression. The study of this cellular individuality has become a field of study in its own right, characterized by a blend of technological development, theoretical analysis, and, more recently, applications to biological phenomena. In this review, we focus on the use of the variability inherent to gene expression as a tool to understand gene regulation.

IRK-1 potassium channels mediate peptidergic inhibition of Caenorhabditis elegans serotonin neurons via a G(o) signaling pathway.

To identify molecular mechanisms that function in G-protein signaling, we have performed molecular genetic studies of a simple behavior of the nematode Caenorhabditis elegans, egg laying, which is driven by a pair of serotonergic neurons, the hermaphrodite-specific neurons (HSNs). The activity of the HSNs is regulated by the G(o)-coupled receptor EGL-6, which mediates inhibition of the HSNs by neuropeptides. We report here that this inhibition requires one of three inwardly rectifying K(+) channels encoded by the C.

Stability of DNA-linked nanoparticle crystals: effect of number of strands, core size, and rigidity of strand attachment.

Three-dimensional ordered lattices of nanoparticles (NPs) linked by DNA have potential applications in novel devices and materials, but most experimental attempts to form crystals result in amorphous packing. Here we use a coarse-grained computational model to address three factors that impact the stability of bcc and fcc crystals formed by DNA-linked NPs : (i) the number of attached strands to the NP surface, (ii) the size of the NP core, and (iii) the rigidity of the strand attachment. We find that allowing mobility in the attachment of DNA strands to the core NP can very slightly increase or decrease melting temperature T(M).