Previous work has shown ultrasound echo decorrelation imaging can track and quantify changes in echo signals to predict thermal damage during in vitro radiofrequency ablation (RFA). In the in vivo studies reported here, the feasibility of using echo decorrelation imaging as a treatment monitoring tool is assessed. RFA was performed on a normal swine liver (N = 5) and ultrasound ablation using image-ablate arrays was performed on a rabbit liver implanted with VX2 tumors (N = 2). Echo decorrelation and integrated backscatter were computed from Hilbert transformed pulse-echo data acquired during RFA and ultrasound ablation treatments. Receiver operating characteristic (ROC) curves were employed to assess the ability of echo decorrelation imaging and integrated backscatter to predict ablation. Area under the ROC curves (AUROC) was determined for RFA and ultrasound ablation using echo decorrelation imaging. Ablation was predicted more accurately using echo decorrelation imaging (AUROC 0.832 and 0.776 for RFA and ultrasound ablation respectively) than using integrated backscatter (AUROC 0.734 and 0.494).
Diversification of neuron classes is essential for functions of the olfactory system, but the underlying mechanisms that generate individual olfactory neuron types are only beginning to be understood. Here we describe a role of the highly conserved HMG-box transcription factor SOX-2 in postmitotic specification and alternative differentiation of the Caenorhabditis elegans AWC and AWB olfactory neurons. We show that SOX-2 partners with different transcription factors to diversify postmitotic olfactory cell types. SOX-2 functions cooperatively with the OTX/OTD transcription factor CEH-36 to specify an AWC "ground state," and functions with the LIM homeodomain factor LIM-4 to suppress this ground state and drive an AWB identity instead. Our findings provide novel insights into combinatorial codes that drive terminal differentiation programs in the nervous system and reveal a biological function of the deeply conserved Sox2 protein that goes beyond its well-known role in stem cell biology.
The assembly of functional neural circuits is critical for complex thoughts, behavior and general brain function. Precise construction of neural circuits requires orderly transition of sequential events from axon outgrowth, pathfinding, branching, to synaptogenesis. Each of these steps is required to be tightly regulated in order to achieve meticulous formation of neuronal connections. MicroRNAs (miRNAs), which silence gene expression post-transcriptionally via either inhibition of translation or destabilization of messenger RNAs, have emerged as key regulators of neuronal connectivity. The expression of miRNAs in neurons is often temporally and spatially regulated, providing critical timing and local mechanisms that prime neuronal growth cones for dynamic responses to extrinsic cues. Here we summarize recent findings of miRNA regulation of neuronal connectivity in a variety of experimental platforms.
Asymmetries in the nervous system have been observed throughout the animal kingdom. Deviations of brain asymmetries are associated with a variety of neurodevelopmental disorders; however, there has been limited progress in determining how normal asymmetry is established in vertebrates. In the C. elegans chemosensory system, two pairs of morphologically symmetrical neurons exhibit molecular and functional asymmetries. This review focuses on the development of antisymmetry of the pair of AWC olfactory neurons, from transcriptional regulation of general cell identity, establishment of asymmetry through neural network formation and calcium signaling, to the maintenance of asymmetry throughout the life of the animal. Many of the factors that are involved in AWC development have homologs in vertebrates, which may potentially function in the development of vertebrate brain asymmetry.
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