Genomic organization, fine-mapping, and expression of the human islet-brain 1 (IB1)/c-Jun-amino-terminal kinase interacting protein-1 (JIP-1) gene

Islet-brain 1 (IB1), a regulator of the pancreatic beta-cell function in the rat, is homologous to JIP-1, a murine inhibitor of c-Jun amino-terminal kinase (JNK). Whether IB1 and JIP-1 are present in humans was not known. We report the sequence of the 2133-bp human IB1 cDNA, the expression, structure, and fine-mapping of the human IB1 gene, and the characterization of an IB1 pseudogene. Human IB1 is 94% identical to rat IB1. The tissue-specific expression of IB1 in human is similar to that observed in rodent. The IB1 gene contains 12 exons and maps to chromosome 11 (11p11.2-p12), a region that is deleted in DEFECT-11 syndrome. Apart from an IB1 pseudogene on chromosome 17 (17q21), no additional IB1-related gene was found in the human genome. Our data indicate that the sequence and expression pattern of IB1 are highly conserved between rodent and human and provide the necessary tools to investigate whether IB1 is involved in human diseases.     

Time-dependent effects of repeated amphetamine treatment on norepinephrine in the hypothalamus and hippocampus assessed with in vivo microdialysis

The effects of repeated amphetamine (AMPH) pretreatment on norepinephrine (NE) neurotransmission in the hypothalamus and hippocampus were assessed using in vivo microdialysis. Rats were pretreated with either saline or an escalating-dose AMPH regimen (1-->10 mg/kg) over 10 consecutive days, and then were withdrawn from AMPH for either 1 day or 30 days, at which time the animals underwent two consecutive days of testing. As expected, repeated treatment with AMPH resulted in time-dependent changes in both spontaneous locomotor activity and in the psychomotor response to a subsequent challenge injection of AMPH. In addition, repeated exposure to AMPH resulted in time-dependent and regionally-specific changes in the basal concentrations of NE in dialysate, and in the NE response to an AMPH challenge. For example, AMPH pretreatment produced a persistent (at least one month) increase in the basal concentration of NE in the hippocampus, but not the hypothalamus, although the response to an AMPH challenge was altered in both structures. It is suggested that AMPH treatment produces adaptations in NE systems that far outlast the acute effects of the drug, and that these may contribute to both transient and more persistent behavioral sequelae associated with the discontinuation of chronic AMPH use.     

Flat plate drag in a micropolar fluid

Summary The drag experienced in a micropolar fluid is investigated by considering uniform streaming past a flat plate. Some recent results on the fundamental solution of the Oseenlinearization of the micropolar flow equations are used to reduce the problem to that of solving a scalar integral equation. The integral equation is analyzed by the application of both asymptotic and variational methods. Results indicate that the drag experienced in a micropolar fluid always exceeds that found in the absence of any micropolarity; however one of the parameters which characterizes a micropolar fluid can be used to minimize the drag.With 2 Figures     

Progressive aneurysmal degeneration of cortical venous drainage of dural arteriovenous malformations: case report

OBJECTIVE AND IMPORTANCE: The development of a venous aneurysm associated with dural arteriovenous malformations rarely has been documented in the literature. CLINICAL PRESENTATION: A 64-year-old man with known dural arteriovenous malformations developed a venous aneurysms, as shown on sequential angiograms obtained during 2 years. INTERVENTION: The dural arteriovenous malformations were treated with neuroendovascular embolization and then surgical excision. CONCLUSION: The clinical presentation, diagnosis, and treatment of this unusual case are presented.     

Direct recording of nicotinic responses in presynaptic nerve terminals

Nicotinic acetylcholine receptors are widely expressed in the nervous system, but their functions remain poorly understood. One attractive hypothesis is that the receptors act presynaptically to modulate synaptic transmission. We provide a direct demonstration of presynaptic nicotinic receptors in situ by using whole-cell patch-clamp techniques to record currents in large presynaptic calyces that midbrain neurons form on ciliary neurons. Bath application of nicotine induced inward currents in the calyces capable of generating action potentials that overrode the limited space clamp achievable. The inward currents reversed near 0 mV and showed inward rectification common for neuronal nicotinic receptors. Tetrodotoxin (TTX) blocked the action potentials but not the inward currents. alpha-Bungarotoxin blocked both, consistent with the presynaptic receptors containing alpha7 subunits. Recording from the postsynaptic ciliary neurons during nicotine exposure revealed EPSCs that TTX blocked, presumably by blocking presynaptic action potentials. The postsynaptic cells also displayed bimodal inward currents caused by their own nicotinic receptors; the bimodal currents were not blocked by TTX but were blocked partially by alpha-bungarotoxin and completely by D-tubocurarine. Dye-filling with Lucifer yellow from the recording pipette confirmed the identity of patched structures and showed no dye transfer between calyx and ciliary neuron. When calyces or ciliary neurons were labeled en mass with neurobiotin and biocytin through nerve roots, dye transfer was rarely observed. Thus, electrical synapses were infrequent and unlikely to influence calyx responses. Immunochemical analysis of preganglionic nerve extracts identified receptors that bind alpha-bungarotoxin and contain alpha7 subunits. The results unambiguously document the existence of functional presynaptic nicotinic receptors.