Chronic granulomatous disease (CGD) is caused by a congenital defect in phagocyte reduced nicotinamide dinucleotide phosphate (NADPH) oxidase production of superoxide and related species. It is characterized by recurrent life-threatening bacterial and fungal infections and tissue granuloma formation. We have created a mouse model of CGD by targeted disruption of p47phox, one of the genes in whi...

Glucocorticoid receptors (GRs) are ligand-dependent transcription modulators. They belong to a superfamily of nuclear hormone receptors including receptors for steroid and thyroid hormones, retinoids, vitamin D and peroxisomal activators among others (1). The receptor can be divided into three functional domains: (1) an N-terminal activation domain (AF1 or t1); (2) a central DNA-binding domain;...

Cost-Based Abduction (CBA) is an AI model for reasoning under uncertainty. In CBA, evidence to be explained is treated as a goal which is true and must be proven. Each proof of the goal is viewed as a feasible explanation and has a cost equal to the sum of the costs of all hypotheses that are assumed to complete the proof. The aim is to find the Least Cost Proof. This paper uses CBA to develop ...

Spino-Cerebellar-Ataxia type 38 (SCA38) is caused by missense mutations in the very long chain fatty acid elongase 5 gene, ELOVL5. The main clinical findings in this disease are ataxia, hyposmia and cerebellar atrophy. Mice in which Elovl5 has been knocked out represent a model of the loss of function hypothesis of SCA38. In agreement with this hypothesis, Elovl5 knock out mice reproduced the m...

The HMGA1 and HMGA2 genes code for proteins belonging to the High Mobility Group A family. Several genes are negatively or positively regulated by both these proteins, but a number of genes are specifically regulated by only one of them. Indeed, knock-out of the Hmga1 and Hmga2 genes leads to different phenotypes: cardiac hypertrophy and type 2 diabetes in the former case, and a large reduction...

Ferritin, a 24-mer heteropolymer of heavy (H) and light (L) subunits, is the main cellular iron storage protein and plays a pivotal role in iron homeostasis by modulating free iron levels thus reducing radical-mediated damage. The H subunit has ferroxidase activity (converting Fe(II) to Fe(III)), while the L subunit promotes iron nucleation and increases ferritin stability. Previous studies on ...

Retinal ganglion cells show direction selectivity in their responses to moving stimuli. The circuitry necessary to generate directional selectivity in these cells has been long debated. Yoshida et al. (2001) use immunotoxin-mediated cell ablation to demonstrate that the starburst amacrine cell is at the core of this computation.

A 'gene knockout' or 'knockout' is a mutation that inactivates a gene function. These mutations are very useful for classical genetic studies as well as for modern techniques including functional genomics. In the past, knockouts of bacterial genes were often made by transposon mutagenesis. In this case, laborious screens are required to find a knockout in the gene of interest. Knockouts of othe...

Two-nucleon removal (or knock-out) reactions at intermediate energies are a developing tool for both nuclear spectroscopy and for the study of certain nucleon correlations in very exotic and some stable nuclei. We present an overview of these reactions with specific emphasis on the nature of the two-nucleon correlations that can be probed. We outline future possibilities and tests needed to ful...

Narcolepsy is characterized by excessive sleepiness and cataplexy, sudden episodes of muscle weakness during waking that are thought to be an intrusion of rapid eye movement sleep muscle atonia into wakefulness. One of the most striking aspects of cataplexy is that it is often triggered by strong, generally positive emotions, but little is known about the neural pathways through which positive ...