On-line, voluntary control of human temporal lobe neurons

Daily life continually confronts us with an exuberance of external, sensory stimuli competing with a rich stream of internal deliberations, plans and ruminations. The brain must select one or more of these for further processing. How this competition is resolved across multiple sensory and cognitive regions is not known; nor is it clear how internal thoughts and attention regulate this competition. Recording from single neurons in patients implanted with intracranial electrodes for clinical reasons, here we demonstrate that humans can regulate the activity of their neurons in the medial temporal lobe (MTL) to alter the outcome of the contest between external images and their internal representation. Subjects looked at a hybrid superposition of two images representing familiar individuals, landmarks, objects or animals and had to enhance one image at the expense of the other, competing one. Simultaneously, the spiking activity of their MTL neurons in different subregions and hemispheres was decoded in real time to control the content of the hybrid. Subjects reliably regulated, often on the first trial, the firing rate of their neurons, increasing the rate of some while simultaneously decreasing the rate of others. They did so by focusing onto one image, which gradually became clearer on the computer screen in front of their eyes, and thereby overriding sensory input. On the basis of the firing of these MTL neurons, the dynamics of the competition between visual images in the subject's mind was visualized on an external display.     

Silymarin,an inhibitor of lipoxygenase

Summary Silybin (I), silydianin (II) and, silychristin (III), the main constituents, of silymarin, non-competitively inhibit the lipoxygenase from soybeans (EC 1.13.11.12) in vitro.F. Fiebrich, Thesis, University of Vienna 1977.H. Koch, Dt. ApothZtg118, 1844 (1978); reported in part at the Colloquium Pharmaceuticum in Münster, 21 st November 1978.     

Human embryonic stem cell-derived neurons establish region-specific, long-range projections in the adult brain

While the availability of pluripotent stem cells has opened new prospects for generating neural donor cells for nervous system repair, their capability to integrate with adult brain tissue in a structurally relevant way is still largely unresolved. We addressed the potential of human embryonic stem cell-derived long-term self-renewing neuroepithelial stem cells (lt-NES cells) to establish axonal projections after transplantation into the adult rodent brain. Transgenic and species-specific markers were used to trace the innervation pattern established by transplants in the hippocampus and motor cortex. In vitro, lt-NES cells formed a complex axonal network within several weeks after the initiation of differentiation and expressed a composition of surface receptors known to be instrumental in axonal growth and pathfinding. In vivo, these donor cells adopted projection patterns closely mimicking endogenous projections in two different regions of the adult rodent brain. Hippocampal grafts placed in the dentate gyrus projected to both the ipsilateral and contralateral pyramidal cell layers, while axons of donor neurons placed in the motor cortex extended via the external and internal capsule into the cervical spinal cord and via the corpus callosum into the contralateral cortex. Interestingly, acquisition of these region-specific projection profiles was not correlated with the adoption of a regional phenotype. Upon reaching their destination, human axons established ultrastructural correlates of synaptic connections with host neurons. Together, these data indicate that neurons derived from human pluripotent stem cells are endowed with a remarkable potential to establish orthotopic long-range projections in the adult mammalian brain.     

Cross-linked surface Ig attaches to actin

In lymphocytes and P3 myeloma cells, cross-linking of surface Ig by the capping and patching phenomenon has been used to demonstrate the induction of a specific association between surface Ig and cellular actin.     

Isoprenylation in regulation of signal transduction by G-protein-coupled receptor kinases.

Rhodopsin kinase and beta-adrenergic receptor kinase (beta ARK) are related members of a serine/threonine kinase family that specifically initiate deactivation of G-protein-coupled receptors. After stimulus-mediated receptor activation, these cytoplasmic kinases translocate to the plasma membrane. Here we show that the molecular basis for this event involves a class of unsaturated lipids called isoprenoids. Covalent modification in vivo of rhodopsin kinase by a 15-C (farnesyl) isoprenoid enables the kinase to anchor to photon-activated rhodopsin. Mutations that alter or eliminate the isoprenoid, fully disable light-specific Rhodopsin kinase translocation. Other receptor kinases (such as beta ARK), which lack an intrinsic lipid, are activated on exposure to brain beta gamma subunits of the signal-transducing G proteins, the gamma subunit of which bears a 20-C (geranylgeranyl) isoprenoid. Using chimaeric beta ARKs that undergo isoprenylation in vitro, we demonstrate that membrane association and activation of these kinases can occur in the absence of beta gamma. These results indicate that rhodopsin kinase (by means of an integral isoprenoid) and beta ARK (through its association with beta gamma) both rely on the function of isoprenyl moieties for their translocation and activity, illustrating distinct, though related, modes of biological regulation of receptor function.