Multivariate analysis and visualization of splicing correlations in single-gene transcriptomes.

Background: RNA metabolism, through 'combinatorial splicing', can generate enormous structural diversity in the proteome. Alternative domains may interact, however, with unpredictable phenotypic consequences, necessitating integrated RNA-level regulation of molecular composition. Splicing correlations within transcripts of single genes provide valuable clues to functional relationships among molecular domains as well as genomic targets for higher-order splicing regulation.

Profiling the array of Ca(v)3.1 variants from the human T-type calcium channel gene CACNA1G: alternative structures, developmental expression, and biophysical variations.

We describe the regulated transcriptome of CACNA1G, a human gene for T-type Ca(v)3.1 calcium channels that is subject to extensive alternative RNA splicing. Fifteen sites of transcript variation include 2 alternative 5'-UTR promoter sites, 2 alternative 3'-UTR polyadenylation sites, and 11 sites of alternative splicing within the open reading frame.

A profile of alternative RNA splicing and transcript variation of CACNA1H, a human T-channel gene candidate for idiopathic generalized epilepsies.

Highly alternatively spliced genes may provide complex targets for disease mutations. Structural changes created by missense mutations may differentially affect the activity of alternative gene products, whereas missense, silent and non-coding mutations may alter developmental regulation of splice variant expression. CACNA1H is a human gene encoding Ca(v)3.

Evaluation of the stability of intracortical microelectrode arrays.

In order to use recorded neural activities from the brain as control signals for neuroprosthesis devices, it is important to maintain a stable interface between chronically implanted microelectrodes and neural tissue. Our previous paper introduced a method to quantify the stability of the recording microelectrodes. In this paper, the method is refined 1) by incorporating stereotypical behavioral patterns into the spike sorting program and 2) by using a classifier based on Bayes theorem for assigning the recorded action potentials to the underlying neural generators.

The effect of higher order RNA processes on changing patterns of protein domain selection: a developmentally regulated transcriptome of type 1 inositol 1,4,5-trisphosphate receptors.

The domain structure of proteins synthesized from a single gene can be remodeled during tissue development by activities at the RNA level of gene expression. The impact of higher order RNA processing on changing patterns of protein domain selection may be explored by systematically profiling single-gene transcriptomes. itpr1 is one of three mammalian genes encoding receptors for the second messenger inositol 1,4,5-trisphosphate (InsP3).

Over-pulsing degrades activated iridium oxide films used for intracortical neural stimulation.

Microelectrodes using activated iridium oxide (AIROF) charge-injection coatings have been pulsed in cat cortex at levels from near-threshold for neural excitation to the reported in vitro electrochemical charge-injection limits of AIROF. The microelectrodes were subjected to continuous biphasic current pulsing, using an 0.4V (versus Ag|AgCl) anodic bias with equal cathodal and anodal pulse widths, for periods up to 7h at a frequency of either 50Hz or 100Hz.

Arrays for chronic functional microstimulation of the lumbosacral spinal cord.

Our objective is to develop neural prostheses based on an array of microelectrodes implanted into the sacral spinal cord, that will allow persons with spinal cord injuries to regain control of their bladder and bowels. For our chronic cat model, we have developed two microelectrode arrays, one type containing nine discrete activated iridium microelectrodes and the second utilizing silicon substrate probes with multiple electrode sites on each probe. Both types can elicit an increase in the pressure within the urinary bladder of more than 40-mm Hg and/or relaxation of the urethral sphincter.

Systematic identification of splice variants in human P/Q-type channel alpha1(2.1) subunits: implications for current density and Ca2+-dependent inactivation.

P/Q-type (Ca(v)2.1) calcium channels support a host of Ca2+-driven neuronal functions in the mammalian brain. Alternative splicing of the main alpha1A (alpha1(2.

The effects of prolonged intracortical microstimulation on the excitability of pyramidal tract neurons in the cat.

This study was conducted to examine the excitability changes induced in cerebral cortical neurons during prolonged microstimulation with a spatially dense microelectrodes array. The arrays of 16 iridium microelectrodes were implanted chronically into the postcruciate gyrus of cats. Neuronal responses characteristic of single pyramidal tract axons (ULRs) were recorded in the medullary pyramid.