Trak1 mutation disrupts GABA(A) receptor homeostasis in hypertonic mice

Hypertonia, which results from motor pathway defects in the central nervous system (CNS), is observed in numerous neurological conditions, including cerebral palsy, stroke, spinal cord injury, stiff-person syndrome, spastic paraplegia, dystonia and Parkinson disease. Mice with mutation in the hypertonic (hyrt) gene exhibit severe hypertonia as their primary symptom. Here we show that hyrt mutant mice have much lower levels of gamma-aminobutyric acid type A (GABA(A)) receptors in their CNS, particularly the lower motor neurons, than do wild-type mice, indicating that the hypertonicity of the mutants is likely to be caused by deficits in GABA-mediated motor neuron inhibition. We cloned the responsible gene, trafficking protein, kinesin binding 1 (Trak1), and showed that its protein product interacts with GABA(A) receptors. Our data implicate Trak1 as a crucial regulator of GABA(A) receptor homeostasis and underscore the importance of hyrt mice as a model for studying the molecular etiology of hypertonia associated with human neurological diseases.     

Alkaloids ofaspidosperma melanocalyx muell-arg

Zusammenfassung InA spidosperma melanocalyx wurde N-Acetyl-16, 17-dihydroxy-aspidospermin (Desmethylaspidocarpin) gefunden sowie dessen durch oxydative Dimerisierung entstandenes Produkt. Die Strukturaufklärung basiert auf physikalisch-chemischen Methoden.     

Radioimmune, radiobinding and HPLC analysis of 2-5A and related oligonucleotides from intact cells

The enzyme (2-5A synthetase) which synthesizes ppp(A2'p)nA where n=2 to 4 (collectively referred to as 2-5A) is widely distributed in a variety of cells and tissues in amounts which increase response to interferon and vary with growth and hormone status. 2-5A activates a nuclease which inhibits protein synthesis. The non-phosphorylated 'core' of 2-5A ((A2'p)nA, n=2 to 4) can inhibit DNA synthesis and cell growth. Here we describe convenient and sensitive radioimmune (RI) and radiobinding (RB) assays for core and 2-5A. In combination with more satisfactory high performance liquid chromatography (HPCL) methods using reverse-phase C18 columns, these assays have been used to detect core and 2-5A in crude extracts from interferon-treated cells. The novel 2-5A synthetase products NAD2'p5' A2'p5'A and A5'p45'A2'p5'A2'p5'A (ref. 13), which can also be detected using the RB assay, were not found in significant amounts. The natural occurrence of core has not been described previously.     

Topography of contextual modulations mediated by short-range interactions in primary visual cortex.

Neurons in primary visual cortex (V1) respond differently to a simple visual element presented in isolation from when it is embedded within a complex image. This difference, a specific modulation by surrounding elements in the image, is mediated by short- and long-range connections within V1 and by feedback from other areas. Here we study the role of short-range connections in this process, and relate it to the layout of local inhomogeneities in the cortical maps of orientation and space. By measuring correlation between neuron pairs located in optically imaged maps of V1 orientation columns we show that the strength of local connections between cells is a graded function of lateral separation across cortex, largely radially symmetrical and relatively independent of orientation preferences. We then show the contextual influence of flanking visual elements on neuronal responses varies systematically with a neuron's position within the cortical orientation map. The strength of this contextual influence on a neuron can be predicted from a model of local connections based on simple overlap with particular features of the orientation map. This indicates that local intracortical circuitry could endow neurons with a graded specialization for processing angular visual features such as corners and T junctions, and this specialization could have its own functional cortical map, linked with the orientation map.