Transient Deactivation Research Articles

Movement rate effect on activation and functional coupling of motor cortical areas.

We investigated changes in the activation and functional coupling of bilateral primary sensorimotor (SM1) and supplementary motor (SMA) areas with different movement rates in eight normal volunteers. An auditory-cued repetitive right-thumb movement was performed at rates of 0.5, 0.75, 1, 2, 3, and 4 Hz. As a control condition, subjects listened to pacing tones with no movements. Electroencephalogram (EEG) was recorded from 28 scalp electrodes and electromyogram was obtained from the hand muscles. The event-related changes in EEG band-power (ERpow: activation of each area) and correlation (ERcor: functional coupling between each pair of cortical areas) were computed every 32 ms. Modulations of ERpow and ERcor were inspected in alpha (8-12 Hz) and beta (16-20 Hz) bands. Motor cortical activation and coupling was greater for faster movements. With increasing movement rate, the timing relationship between movement and tone switched from synchronization (for 0.5-1 Hz) to syncopation (for 3-4 Hz). The results suggested that for slow repetitive movements (0.5-1 Hz), each individual movement is separately controlled, and EEG activation and coupling of the motor cortical areas were immediately followed by transient deactivation and decoupling, having clear temporal modulation locked to each movement. In contrast, for fast repetitive movements (3-4 Hz), it appears that the rhythm is controlled and the motor cortices showed sustained EEG activation and continuous coupling.

Interplay between activation of GIRK current and deactivation of Ih modifies temporal integration of excitatory input in CA1 pyramidal cells.

Trains of brief iontophoretic glutamate pulses were delivered onto the apical dendrites of CA1 pyramidal cells at variable frequencies (3-100 Hz) to examine how the activation of a G protein-activated, inwardly rectifying K(+) (GIRK) conductance alters the postsynaptic processing of repetitive excitatory input. Application of the GIRK channel agonist baclofen (20 microM) reduced the amplitude of individual glutamate-evoked postsynaptic potentials (GPSPs) and attenuated summation of GPSPs so that higher stimulus intensities were required to fire the cell. Notably, GIRK channel activation not only decreased GPSPs, but also suppressed the subsequent afterhyperpolarization (AHP), which arises from a transient deactivation of the hyperpolarization-activated cation current (I(h)). Voltage-clamp recordings ruled out a direct modulatory action of baclofen on I(h). GIRK channel activation alone accounts for AHP suppression, firstly because, with smaller GPSP amplitudes, fewer I(h) channels are deactivated, resulting in a diminished AHP, and secondly because, owing to its progressive increase in the hyperpolarizing direction, the GIRK conductance shunts a large portion of the remaining AHP. We provide experimental evidence that the suppression of the I(h)-dependent AHP by GIRK channel activation bears particular significance on the processing of repetitive excitatory inputs at frequencies at which the deactivation kinetics of I(h) exert a prominent depressing effect. In functional terms, activation of GIRK current not only produces a time-independent mitigation of incoming excitatory input, which results directly from the opening of an instantaneous K(+) conductance, but might also cause a time-dependent redistribution of synaptic weight within a stimulus train, which we link to an interplay with the deactivation of I(h).

Transient deactivation of ERK signalling is sufficient for stable entry into G0 in primary avian fibroblasts.

Re-entry into the cell cycle from quiescence requires the activation of mitogen-activated protein (MAP) kinases of the extracellular-signal-regulated kinase (ERK) family [1,2]. The relationship between ERK and cell-cycle control is, however, complex, as ERK activation can also lead to terminal differentiation [3] or a senescence-like growth arrest [4]. Here, we report that reversible cell-cycle exit induced by serum withdrawal in primary avian fibroblasts is associated with rapid deactivation of ERK, but ERK activity is subsequently regenerated and sustained at high levels in fully quiescent (G0) cells. As in proliferating cells, ERK activation during G0 required the MAPkinase kinase MEK and was partially dependent on cell adhesion. Active, phosphorylated ERK was concentrated in the nucleus in cycling cells, but was largely confined to the cytoplasm during G0. This was unexpected, as activatory phosphorylation mediated by MEK is thought to play an important role in promoting nuclear translocation [5,6]. These results indicate that transient deactivation of ERK signalling can be sufficient for stable cell-cycle exit, and that MEK-mediated phosphorylation is not sufficient for nuclear translocation of active ERK in G0. Cytoplasmic sequestration may prevent active ERK from accessing critical nuclear cell-cycle targets, thus allowing quiescent or post-mitotic cells to retain ERK activity for other physiological functions.

Adiabatic prereforming of hydrocarbons — an important step in syngas production

Adiabatic prereforming is a well-established process in modern syngas production and implies both economic and operational benefits. The adiabatic prereformer converts hydrocarbon feed-stocks by steam reforming reactions in the low temperature range, 350–550°C. Design aspects of adiabatic prereforming are reviewed. Reaction kinetics, poisoning and transient deactivation and limits for carbon formation have been formulated as mathematical models and implemented into reactor simulation programs. Operation close to the carbon limits are illustrated by examples from experimental development work. Industrial operation and benefits are illustrated by examples from units operating in plants producing hydrogen, ammonia and carbon monoxide.

Signal transduction by the cytoplasmic domains of Fc epsilon RI-gamma and TCR-zeta in rat basophilic leukemia cells.

The gamma subunit of the high affinity IgE receptor, Fc epsilon RI, is a member of a family of proteins which form disulfide-linked dimers. This family also includes the zeta- and eta-chains of the T cell receptor. Engagement of Fc epsilon RI activates src-related protein tyrosine kinases in basophils and mast cells. However, the role of individual subunits of Fc epsilon RI in this activation is still not known. In an effort to determine the function of Fc epsilon RI-gamma, we used chimeric proteins containing the extracellular and transmembrane domains of the alpha chain of the human interleukin 2 receptor (Tac) and the cytoplasmic domains of either T cell receptor-zeta or Fc epsilon RI-gamma. We show that while cross-linking of the Tac chimeras in the rat basophilic leukemia cell line RBL-2H3 resulted in the tyrosine phosphorylation of a subset of proteins and a portion of the degranulation normally observed after Fc epsilon RI-mediated stimulation, no detectable activation of p56lyn or pp60c-src was observed. In contrast, an apparent transient deactivation of these two kinases was observed after Tac chimera cross-linking. These observations suggest that Fc epsilon RI-gamma is responsible for some, but not all, of the signaling that occurs after engagement of its receptor, and that other receptor subunits may also play important roles in this signaling process.

Regulation of protein serine-threonine phosphatase type-2A by tyrosine phosphorylation.

Extracellular signals that promote cell growth activate cascades of protein kinases. The kinases are dephosphorylated and deactivated by a single type-2A protein phosphatase. The catalytic subunit of type-2A protein phosphatase was phosphorylated by tyrosine-specific protein kinases. Phosphorylation was enhanced in the presence of the phosphatase inhibitor okadaic acid, consistent with an autodephosphorylation reaction. More than 90% of the activity of phosphatase 2A was lost when thioadenosine triphosphate was used to produce a thiophosphorylated protein resistant to autodephosphorylation. Phosphorylation in vitro occurred exclusively on Tyr307. Phosphorylation was catalyzed by p60v-src, p56lck, epidermal growth factor receptors, and insulin receptors. Transient deactivation of phosphatase 2A might enhance transmission of cellular signals through kinase cascades within cells.