Pathway input

Murray PJ. 2007. The JAK-STAT signaling pathway Input and output integration. J Immunol. 178 2623-2629. 

There are also deficits in gain control and integration of stimuli in schizophrenia that may involve aberrant lateral interactions and/or impaired visual pathway input (Silverstein et al., 2000 Doniger et al., 2002 Must et al., 2004 Dakin et al., 2005 Johnson et al., 2005 Uhlhaas et al., 2006b Kurylo et al., 2007 Butler et al., 2008), although more work is needed to understand the substrates of gain control and integration. 

A product of the second pathway, NjO, is a significant greenhouse gas. About a quarter of the annual input of NjO to the atmosphere comes from the ocean. 

Surface water enrichment is the result of aeolian and fluvial inputs, which are thought to be the most important sources of Th to the ocean. Thorinm-232 has been proposed as a link between the radiogenic thorium isotopes and trace metals and anthropogenic pollutants. " While the pathways are very different for the radiogenic thorium isotopes, Th is delivered to the ocean in a fashion similar to many pollutants and trace metals. For example, Guo et found Th distributions in the Gulf of Mexico and off Cape Hatteras in the North Atlantic Ocean agreed well with the general distribution pattern of aluminum. 

The nucleus accumbens is part of the limbic system. It receives dopaminergic input through the mesolimbic system that originates from cell bodies in the ventral segmental area (A 10 cell group). This mesolimbic dopaminergic pathway is part of the reward pathways. Drugs of abuse (cocaine, amphetamine, opiates or nicotine) have been shown to increase the level of dopamine release in these neurons. 

The smooth muscle cell does not respond in an all-or-none manner, but instead its contractile state is a variable compromise between diverse regulatory influences. While a vertebrate skeletal muscle fiber is at complete rest unless activated by a motor nerve, regulation of the contractile activity of a smooth muscle cell is more complex. First, the smooth muscle cell typically receives input from many different kinds of nerve fibers. The various cell membrane receptors in turn activate different intracellular signal-transduction pathways which may affect (a) membrane channels, and hence, electrical activity (b) calcium storage or release or (c) the proteins of the contractile machinery. While each have their own biochemically specific ways, the actual mechanisms are for the most part known only in outline. 

Because of its motor, i.e., activating effect on vascular smooth muscle and its inhibitory effect on intestinal smooth muscle, the sympathetic nervous system has been cast into the role of the component of the nervous system that executes control of visceral function in times of physical emergency for the organism. The phrase fight or flight has been often used to describe the circumstances in which the adrenergic transmitters of the sympathetic system are dominant over the cholinergic parasympathetic system. This concept is perhaps oversimplified but it has the utility of a first approximation of how the two components of the ANS interact in the periphery. Sensory inputs which lead to increased blood pressure, for example, activate the sympathetic pathways. 

Elias, R.W., Hirao, Y. and Patterson, C.C. 1982 The circumvention of the natural hiopurification of calcium along nutrient pathways hy atmospheric inputs of industrial lead. Geochimica et Cosmochimica Acta 46 2561-2580. 

An alternative pathway for activating the cascade has recently been demonstrated in which factor XII is absent from the reaction mixture [42-45]. Two different groups have isolated two different proteins, each of which seems to activate the HK-prekallikrein complex. One is heat-shock protein 90 [46] and the other is a prolylcarboxypeptidase [47]. Neither protein is a direct prekallikrein activator as is factor Xlla or factor Xllf because each activator requires HK to be complexed to the prekallikrein. In addition, the reaction is stoichiometric, thus the amount of prekallikrein converted to kallikrein equals the molar input of heat-shock protein 90 (or prolylcarboxypeptidase). These proteins can be shown to contribute to factor Xll-independent prekallikrein activation and antisera to each protein have been shown to inhibit the process. When whole endothelial cells are incubated with normal plasma or factor Xll-deficient plasma, the rate of activation of the deficient plasma is very much slower than that of the normal plasma, the latter being factor Xll-dependent [45]. Under normal circumstances (with factor XII present), formation of any kallikrein will lead to factor Xlla formation even if the process were initiated by one of these cell-derived factors. 

Table 10.4 lists the rate parameters for the elementary steps of the CO + NO reaction in the limit of zero coverage. Parameters such as those listed in Tab. 10.4 form the highly desirable input for modeling overall reaction mechanisms. In addition, elementary rate parameters can be compared to calculations on the basis of the theories outlined in Chapters 3 and 6. In this way the kinetic parameters of elementary reaction steps provide, through spectroscopy and computational chemistry, a link between the intramolecular properties of adsorbed reactants and their reactivity Statistical thermodynamics furnishes the theoretical framework to describe how equilibrium constants and reaction rate constants depend on the partition functions of vibration and rotation. Thus, spectroscopy studies of adsorbed reactants and intermediates provide the input for computing equilibrium constants, while calculations on the transition states of reaction pathways, starting from structurally, electronically and vibrationally well-characterized ground states, enable the prediction of kinetic parameters. 

In a classical neural pathway, such as that depicted in Fig. 1.3, neuron A must excite neuron B and at the same time inhibit neuron C in order to optimise the excitation of B. It could achieve this with one NT able to activate receptors linked to different events on B and C. Of course, neuron C would have other inputs, some of which would be excitatory and if the same NT was used it could activate the inhibitory mechanism on C as well. Also, the NT released from A might be able to stimulate as well as inhibit neuron C (Fig. 1.3(a)). Even the provision of separate receptors linked to excitation and inhibition would not overcome these problems since both would be accessible to the NT. One possible solution, used in the CNS, is to restrict the NT to the synapse at which it is released by structural barriers or rapid degradation. Also the inputs and receptors linked to excitation could be separated anatomically from those linked to inhibition and, in fact, there is electrophysiological and morphological evidence that excitatory synapses are mainly on dendrites and inhibitory ones on the soma of large neurons (Fig. 1.3(b)). Nevertheless, the problem of overlap would be eased if two NTs were released, one to activate only those receptors linked to excitation and another to evoke just inhibition, i.e. place the determinant of function partly back on the NT (Fig. 1.3(c)). This raises a different problem which has received much consideration. Can a neuron release more than one NT ... 

Figure 15.2(b) A schematic presentation of possible basal ganglia circuitry in Parkinson s disease. In PD there is little or no inhibitory nigrostriatal input to the striatum so the Ind Path is active and GPext is inhibited. This will then have less depressant effect on the SThN which will be free to drive the GPint (and SNr) and so reduce cortico-thalamic traffic and produce akinesia. See text for detail. Pathway activity — low — normal — high... 

Figure 15.9 Peptide modulation of striatal input to the globus pollidus. Enkephalin released from axon terminals of neurons of the indirect pathway (see Fig. 15.2 for details) is thought to inhibit GABA release from the same terminals so that feedback (auto) inhibition is reduced. This will free the neurons to inhibit the subthalamic nucleus (SThN) and its drive to GPint and SNr which in turn will have less inhibitory effect on cortico-thalamic traffic and possibly reduce akinesia. Dynorphin released from terminals of neurons of the direct pathway may also reduce glutamate release and excitation in the internal globus pallidus and further depress its inhibition of the cortico-thalamic pathway. High concentrations of these peptides may, however, result in dyskinesias. (See Henry and Brotchie 1996 and Maneuf et al. 1995)...

The cells comprising lamina V are more diverse than those of lamina IV and their dendrites extend vertically toward the superficial layers. Cell bodies in lamina V contribute to three projection pathways, the SCT, PSDC and STT. However, the STT cells appear to be predominant in this lamina. Lamina V plays an important role in nociception since it receives both A - and C-fibre inputs. Some cells in lamina V also respond to cutaneous low- and high-threshold mechanical stimuli and receive nociceptive inputs from the viscerae. Many of these neurons also project onto mononeurons and so act as interneurons in the polysynaptic withdrawal reflex to noxious stimuli. 

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