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A recombination system has been developed for efficient chromosome engineering in Escherichia coli by using electroporated linear DNA. A defective lambda prophage supplies functions that protect and recombine an electroporated linear DNA substrate in the bacterial cell. The use of recombination eliminates the requirement for standard cloning as all novel(More)
It has been hypothesized that R-type Ca currents result from the expression of the alpha(1E) gene. To test this hypothesis we examined the properties of voltage-dependent Ca channels in mice in which the alpha(1E) Ca channel subunit had been deleted. Application of omega-conotoxin GVIA, omega-agatoxin IVA, and nimodipine to cultured cerebellar granule(More)
Parkin, an E3 ubiquitin ligase, has been found to be responsible for autosomal recessive juvenile parkinsonism characterized primarily by selective loss of dopaminergic neurons with subsequent defects in movements. However, the molecular mechanisms underlying this neuron loss remain elusive. Here, we characterized Drosophila parkin loss-of-function mutants,(More)
Mutations at the waltzer (v) locus result in deafness and vestibular dysfunction due to degeneration of the neuroepithelium within the inner ear. Here, we use a positional cloning approach to show that waltzer encodes a novel cadherin (Cdh23), which is most closely related to the Drosophila Fat protein. A single nucleotide deletion in the v(J) allele and a(More)
BACKGROUND Pulmonary arterial hypertension (PAH) is a rare but fatal lung disease of diverse origins. PAH is now further subclassified as idiopathic PAH, familial PAH, and associated PAH varieties. Heterozygous mutations in BMPR2 can be detected in 50% to 70% of patients with familial PAH and 10% to 40% of patients with idiopathic PAH. Although endothelial(More)
Analysis of parallel genotyping and expression profiling data has shown that mRNA expression levels are highly heritable. Currently, only a tiny fraction of this genetic variance can be mechanistically accounted for. The influence of trans-acting polymorphisms on gene expression traits is often mediated by transcription factors (TFs). We present a method(More)
Polymeric microparticles have been widely investigated as platforms for delivery of drugs, vaccines, and imaging contrast agents and are increasingly used in a variety of clinical applications. Microparticles activate the inflammasome complex and induce the processing and secretion of IL-1β, a key innate immune cytokine. Recent work suggests that although(More)
Identifying accurate biomarkers of cognitive decline is essential for advancing early diagnosis and prevention therapies in Alzheimer's disease. The Alzheimer's disease DREAM Challenge was designed as a computational crowdsourced project to benchmark the current state-of-the-art in predicting cognitive outcomes in Alzheimer's disease based on high(More)
The growing public threat of Alzheimer's disease (AD) has raised the urgency to discover and validate prognostic biomarkers in order to predicting time to onset of AD. It is anticipated that both whole genome single nucleotide polymorphism (SNP) data and high dimensional whole brain imaging data offer predictive values to identify subjects at risk for(More)
MOTIVATION MicroRNAs (miRNAs) play a key role in regulating tumor progression and metastasis. Identifying key miRNAs, defined by their functional activities, can provide a deeper understanding of biology of miRNAs in cancer. However, miRNA expression level cannot accurately reflect miRNA activity. RESULTS We developed a computational approach, ActMiR, for(More)