Positive Feedback System Research Articles

A review of selected sociobiological principles: Application to hominid evolution: II. The effects of intergroup conflict

This paper is a continuation of the analysis of hominid social structure and its effect on human evolution, centering on the influence of intergroup structure. Using sociobiological theory and comparative ethology, it was determined that hominid groups were probably fairly intolerant of each other, with meetings characterized by mostly limited conflict, with occasional episodes of co-operation or avoidance depending upon the situation. The effect of weapons was examined using game theory, a computer simulation and the idea of the evolutionary stable strategy (ESS). The influence of weapons on the hominid groups' ESS was to shift it toward a much more war-like character, with greatly increased levels of intergroup conflict. This new level of conflict led to a positive feedback system, where conflict selected for greater intelligence, which created better weapons, which then increased selection for conflict and so on. Conflict also selected for a stronger social structure and larger groups. As the hominid groups increased in size and genetic heterogenity, the selective force of intergroup conflict decreased and eventually the positive feedback system was halted. Larger groups also created a pre-adaptation for monogamy by increasing the number of subordinates who could mate (they would be monogamous) and thus the proportion of genes contributed by monogamy to the next generation.

Submersed Vegetation: An Internal Factor in Lake Ecosystem Succession

The accretion rate of sediments in a lake ecosystem is an index of its rate of aging. In shallow eutrophic Lake Wingra, sedimentation is coupled to a positive feedback system involving littoral vegetation, the phytoplankton, and sediments near enough to the water surface for colonization by macrophytes. Rooted plants enrich the water with nutrients and organic matter above the normal resuspension of sediments, thereby stimulating pelagic production and sedimentation that eventually produce more surface area colonizable by macrophytes. Analysis of a budget for colonizable surface area shows that relatively large changes in the rate of colonizable sediment accrual result from small changes in internal loading from sediments and littoral plants, the efficiency of decomposition, and the rate of sedimentation. On the other hand, the rate of accretion of colonizable sediment is relatively insensitive to changes in the influx of phosphorus and dry matter to the lake from the watershed. Internal mechanisms of enrichment such as those described here accelerate the eutrophication of lakes. This tendency toward autogenic eutrophication is not consistent with the hypotheses of lake development proposed by Odum (1969) and Margalef (1975). Evidently the direction and rate of lake succession depend upon basin morphometry and the abundance of littoral vegetation as well as inputs from the watershed.

Methylxanthines modulate adenosine release from slices of cerebral cortex

Using slices of mouse or rat cerebral cortex incubated with [3H]adenosine or [3H]adenine and/or [14C]GABA we have examined factors affecting the release of these compounds, and especially the influence of methylxanthines. Although release of purines and GABA could be induced by ouabain (10(-4) M), or p-hydroxymercuribenzoate (5 x 10(-4) M) no release was produced by ethacrynic acid (10(-3) or 10(-4) M) phenytoin (10(-3) M), noradrenaline or SC 13504. Release is probably not therefore related to (Na+, K+) ATPase or Mg2+-ATPase inhibition. At concentrations of 10(-3) and 10(-4) M, caffeine, theophylline, aminophylline and isobutyl-methylxanthine (IBMX) markedly depressed the release of purines evoked by ouabain. Non-xanthine inhibition of phosphodiesterase had much weaker though statistically significant effects. The methylxanthines had no significant effect on GABA release. It is suggested that the results can be explained on the basis of a positive feedback system in which released adenosine activates membranal adenylate cyclase, and the increased concentration of cyclic AMP which results form or origin of much of the adenosine released subsequently. However, we cannot exclude the existence of an intracellular receptor for methylxanthines which causes directly the inhibition of purine release.

Prostaglandins and articular cartilage metabolism: Does prostaglandin perturbation perpetuate cartilage destruction?

There is sufficient evidence available attesting to the in vitro inhibitory effect that PGs have on articular cartilage metabolism. In view of the indomethacm sensitivity of substances secreted by RS in culture, the elevated levels of PGs found in synovial fluid from rheumatic joints, and the suggestion of the presence of an inflammatory aspect in osteoarthritis, it is becoming suspect that similar circumstances may exist in vivo. That inhibition of proteoglycan synthesis by PGs may play a role in development and/or progression of cartilage changes is compatible with (1) in vitro evidence of a positive feedback system of PC synthesis (hence the vicious cycle terminology) and (2) the essential irreversability of the PG inhibitory effect. However, this inhibition of cartilage metabolism is most readily seen at what must be considered pharmacologic doses. How can we reconcile these effects when levels of endogenous PG are several orders of magnitude less, even in inflammatory disease? Moreover, it is becoming disturbingly clear that various PGs may have opposing metabolic effects (i.e., PGI stimulation of metabolism) so that the overall role of PGs in cellular regulation may be dependent upon the algebraic sum of the various subtypes. These questions must still be addressed, but it is certainly a tenable concept that homeostatic regulation and responsiveness of cartilage to external stimuli (in the absence of neural and vascular elements) may indeed be mediated by PG modulation of metabolism.

Inhibition and excitation of primate spinothalamic tract neurons by stimulation in region of nucleus reticularis gigantocellularis.

1. Electrical stimulation in the region of the nucleus reticularis gigantocellularis (NGc) in anesthetized monkeys inhibited or excited spinothalamic tract neurons in the lumbosacral and cervical enlargements. 2. The descending effects were generally more pronounced for activity evoked by cutaneous A-delta-fibers than for activity produced by large myelinated cutaneous afferents. Nevertheless, the responses to all types of natural stimuli used could be inhibited or facilitated. 3. The excitation from repeated brief stimulus trains to the NGc sometimes increased progressively, suggesting the existence of a positive feedback system. Occasionally, repeated stimulation of the NGc produced a progressively greater inhibition. 4. The threshold stimulus strength to elicit the inhibitory and excitatory actions was usually less than 50 microA, and in some cases less than 25 microA. The inhibition and excitation increased as the stimulus intensity was raised above the threshold value, or as the number and/or frequency of pulses in the stimulus train was increased. 5. The strongest inhibition and excitation was produced by stimulation within the NGc on either side of the brain stem. There was no obvious topographic organization of inhibitory and excitatory zones. 6. Dorsolateral tractotomies in the high cervical spinal cord did not prevent the effects of NGc stimulation, indicating that the inhibitory and excitatory pathways descend in the ventral parts of the white matter. 7. It is suggested that the inhibition and excitation are mediated by the medullary reticulospinal system.

Modification of circadian sleep rhythms by gonadal steroids and the neural mechanisms involved

The effects of gonadectomy and gonadal hormone treatment of castrated rats or ovariectomized (OVX) rats bearing brain lesions on the circadian rhythms of slow wave sleep (SWS) and paradoxical sleep (PS) have been studied under a 14/10 light-dark schedule. Cortical EEGs and dorsal neck EMG were used to monitor SWS, PS and alertness. Intact female rats showed two daytime SWS peaks, one daytime PS peak and a small night PS peak except during proestrus. In intact male rats, the morning SWS peak and night PS peak were variable and SWS and PS peaks in daytime were dissociated. Orchidectomized (ORX) rats showed the morning SWS peak and disrupted the dissociation of SWS and PS peaks. Furthermore, gonadectomy increased the night PS peak. Posterior deafferentation of the hypothalamus (PDM) eliminated the night PS peak. Estradiol (E 2B) injection to long term OVX rats eliminated the night PS peak from the first day of injection. However, E 2B injection into androgenized OVX rats, ORX rats and OVX rats bearing septal lesion or MPO roof cut did not eliminate night PS peak. E 2B injection to short term OVX rats or OVX rats with PDM lesions delayed the E 2B-induced elimination of night PS peak. From these results, it is suggested that: (1) sexual dimorphism exists in the circadian sleep rhythm itself, and this difference partly depends on the hormonal environment produced by sex steroids; (2) the rise and fall of night PS peak reflects the neurohumoral environment in female rats; (3) the appearance of night PS peak involves the abolition of negative feedback of sex steroids and the posterior neural input into hypothalamus; and (4) the elimination of night PS peak on natural proestrus and following E 2B treatment of OVX rats requires the intact positive feedback system of estradiol.

Cell Attraction and Cell-to-Cell Contact

The early stages of conjugation of the ciliate Blepharisma were studied, bearing in mind the general interests, cell attraction and cell-to-cell contact.Miyake's Blepharisma system was introduced as a positive feedback system at first, in which uni-cellular organisms with two mating types secrete respective mating substances GI (gamone I or blepharmone)and GII (gamone II or blepharismone) which have been purified and identified as single molecules. A cell is, by the opposite type of mating sub- stance, enhanced to secrete its mating substance and induced to conjugate. (§2)The mating type I cell was discovered to be specifically attracted by GII, and the type II cell was not attracted by any mating substance. (§3)A mating substance, also, induces ciliary union of a cell pair which advances to glued union later. The ciliary union is participated in by the two kinds of parallel ciliary rows, adoral zone of membranelles (AZM) and anterior extension of undulating membrane (extUM). A mating substance induces AZM and extUM sequentially to become capable to make an AZM-extUM bond. A ciliary row of extUM is also discovered to be significantly attached to the surface of artificial substrata. It will provide an available method for investigation of properties of cellular contact. (§4)

Luteinizing hormone secretion in patients presenting with post-oral contraceptive amenorrhoea: evidence for a hypothalamic feedback abnormality.

Twenty-four patients who presented with amenorrhoea after discontinuing oral contraceptives were studied. In fourteen patients underlying conditions were present which could account for the amenorrhoea. Two patients were pregnant, two had premature ovarian failure and four polycystic ovarian disease. Pituitary tumours were present in three patients, and in another three radiological abnormalities of the pituitary fossa suggested the presence of an intrasellar tumour. Basal serum luteinizing hormone levels reliably differentiated ovarian from hypothalamic or pituitary lesions. Varied patterns of serum LH response to clomiphene were present in the patients with post-oral contraceptive amenorrhoea or pituitary lesions. Most patients showed normal hormone response patterns, with a secondary LH peak, but in others a partial response only was seen. In the latter group, who responded normally to exogenous gonadotrophin releasing hormone, no secondary LH peak occurred despite normal oestradiol responses. This suggests an abnormality of the positive feedback system for oestrogens. Subsequent stimulation with clomiphene produced normal LH responses in these patients showing that the abnormality was reversible. These findings are consistent with the hypothesis that post-oral contraceptive amenorrhoea is the result of continuing suppression of normal hypothalamic pituitary feedback systems after the sex steroids have been stopped. The different patterns of hormone response to clomiphene suggest varying degrees of feedback abnormality, and in some patients the positive feedback mechanism only is impaired.

Brain lesions and precocious puberty in rats.

IN the immature female rat, the ability to secrete the gonadotrophins luteinising hormone (LH) and follicle-stimulating hormone (FSH) in response to a single injection of oestradiol or of progesterone first appears about day 28 of life1,2. Younger animals respond to these hormonal stimuli with an increased release of gonadotrophins only if they have been primed with an injection of oestrogen 3 or more days earlier, and it is assumed that the priming steroid promotes the functional maturation of a positive (stimulatory) feedback system3 by an unknown mechanism. Alternatively, electrolytic lesions in the area of the basal hypothalamus of 23-d-old rats induce precocious sexual maturation leading to pubertal ovulation within 4 or 5 d (ref. 4). The lesion site is rich in luteinising hormone releasing hormone5, and it seems likely that the discharge of this polypeptide triggers the rapid and sustained increase in the production of ovarian steroids, particularly of oestrogen, observed during this period4. We report here that the increase of endogenous steroid in response to a brain stimulus can prime the positive feedback system in a manner closely related to the effect of exogenous oestrogen. This suggests that brain lesions advance the process of sexual maturation through the precocious establishment of a positive feedback loop.

A developmental comparison of steroid-induced and male-induced ovulation in young mice.

Exposure of immature female mice of a particular body weight to an adult male results sequentially in a rapid subovulating release of LH, a dramatic surge in circulating estradiol, and two days later, an ovulating release of LH. The development of this response, using indirect measures such as uterine growth and/or ovulation itself, was the subject of the present research. Preliminary experiments evaluated the ovulatory efficacy of a range of doses of injected estrogen and documented the importance of progesterone in steroid-induced ovulation in young mice. In the primary experiments, immature females were male-exposed, injected with an estradiol-progesterone sequence, or left undisturbed, all treatments lasting for three days and being initiated at all one gram ranges in body weight during the relevant stages of development. As adjudged by uterine growth, the ability to release estrogen in response to a male matures early in the life of a female mouse. The capacity to ovulate in response to three days of male exposure, however, develops much later and simultaneously with the establishment of ovulatory responsiveness to steroid injection. In a related experiment, continuous cohabitation with an adult male from an early age also yielded ovulation concurrently with maturation of ovulatory responsiveness to exogenous steroid. Regardless then of the enhanced secretion of estrogen among female mice cohabiting with males, it may be concluded that their pubertal ovulation is delayed until the independent development of a steroid-sensitive, positive feedback system.

Auroral flares and solar flares

The morphology of development of auroral flares (magnetospheric substorms) for both electron and proton auroras is summarized, based on ground-based as well as rocket-borne and satellite-borne data with specific reference to the morphology of solar flares. The growth phase of an auroral flare is produced by the inflow of the solar wind energy into the magnetosphere by the reconnection mechanism between the solar wind field and the geomagnetic field, thus the neutral and plasma sheets in the magnetotail attaining their minimum thickness with a great stretch of the geomagnetic fluxes into the tail. The onset of the expansion phase of an auroral flare is represented by the break-up of electron and proton auroras, which is associated with strong auroral electrojets, a sudden increase in CNA, VLF hiss emissions and characteristic ULF emissions. The auroral break-up is triggered by the relaxation of stretched magnetic fluxes caused by cutting off of the tail fluxes at successively formed X-type neutral lines in the magnetotail. The resultant field-aligned currents flowing between the tailward magnetosphere and the polar ionosphere produce the field-aligned anomalous resistivity owing to the electrostatic ion-cyclotron waves; the electrical potential drop thus increased further accelerates precipitating charged particles with a result of the intensification of both the field-aligned currents and the auroral electrojet. It seems that the rapid building-up of this positive feedback system for precipitating charged particles is responsible for the break-up of an auroral flare.

The AV nodal Wenckebach phenomenon as a positive feedback mechanism

The AV nodal Wenckebach phenomenon is a manifestation of the operation of a positive feedback mechanism. As AV conduction for a given beat is retarded relative to that for the preceding beat, the action potentials of critical cells in the AV node are prolonged. Hence, the next cardiac impulse arrives at these cells earlier in the relative refractory period, causing still slower AV conduction and still greater action potential prolongation. This process continues until an impulse is blocked, whereupon the cycle begins anew. The positive feedback system may be represented graphically by a curve of the P-R interval plotted as a function of the R-P interval and by a straight line representing the R-P interval as a function of the P-R interval. The curve of P-R as a function of R-P is the forward element of the positive feedback loop, whereas the straight diagonal line describing R-P as a function of P-R is the feedback element of the loop. When the curve intersects the diagonal line, AV conduction will be stable. However, when the curve and diagonal line are displaced so that they no longer intersect, the Wenckebach phenomenon will supervene. The diagonal line will be displaced only by changes in heart rate, whereas the curve will be displaced not only by changes in heart rate but also by variations in autonomic neural tone, electrolyte concentrations, and the levels of certain drugs.

Secretory protein synthesis in the stimulated rat parotid gland. Temporal dissociation of the maximal response from secretion.

Administration of the beta-adrenergic drug, isoproterenol (IPR), affects the release of 98% of stored amylase from rat parotid gland acinar cells. A period of 6 h elapses from the onset of secretion to the maximum [(14)C]phenylalanine (Phe) incorporation into total protein and amylase. 10 h after IPR administration the rate of [(14)C]Phe incorporation into total protein was no longer elevated above that of control. Incorporation into amylase, however, remained elevated above the control by 2.3 times. This latent period may reflect: (a) reduced amounts of available ATP which occurs as a result of the process of secretion as well as (b) the time required for reorganization of cellular organelles and membranes after secretion. The latent period after IPR-induced secretion appears similar to the latent period which has recently been reported to occur after physiologic release of amylase from the parotid gland during the diurnal feeding cycle of the rat. These observations support the existence of a positive feedback system operant in the parotid acinar cell linking the release of secretory proteins with their synthesis. The period of greatest protein synthesis is, however, temporally dissociated from the secretory process.

Penicillin as an epileptogenic agent: effect on an isolated synapse.

Penicillin enhances the excitatory postsynaptic potential of the squid stellate ganglion. This effect suggests the hypothesis that the epileptic focus created by the topical application of penicillin to the mammalian cerebral cortex is produced by the facilitation of excitatory synaptic coupling within the preexisting positive recurrent feedback system.

Recurrent excitation of secondary olfactory neurons: a possible mechanism for signal amplification.

Secondary neurons of the olfactory bulb can be excited monosynaptically after activation of neighboring secondary neurons by antidromic and orthodromic volleys. Recurrent collaterals of secondary neurons are proposed to synapse with other secondary neurons, thus forming a direct recurrent excitatory pathway. Such a positive feedback system could strengthen the original input signal.

Verbal anxiety and the beta adrenergic receptors: a facilitating mechanism?

Since there is evidence that propranolol reduces the intensity of physiological symptoms of anxiety states and psychological anxiety as well, it has been hypothesized that the beta adrenergic receptors may participate in a positive feedback system which facilitates anxiety. Six healthy female subjects were each subjected to mildly stressful hypnotic suggestions on six occasions. During three of the trials on each subject the beta adrenergic blocking agent propranolol was administered. Anxiety levels in recorded speech were measured during each experiment, and changes in plasma free fatty acids were estimated as an indication of beta receptor activation. The results indicate that beta adrenergic blockade with propranolol has no inhibiting effect on psychological anxiety in healthy subjects when an operational measure of anxiety is used, and where bodily symptoms are absent. There is little evidence that the beta receptors participate in a subliminal feedback system which facilitates anxiety, but probably the bodily sensations of anxiety states do tend to intensify psychological anxiety.

Phenolase inhibitor from cultures of Penicillium expansum which may play a part in fruit rotting.

PREVIOUS work in this laboratory1 has shown that the light colour of apples infected with Penicillium expansum (“blue-mould”) is due to the inhibition by the fungus of the fruit's normal enzymatic browning system. A positive feedback system operates whereby the fungal pectolytic enzymes modify the apple's phenolics to yield inhibitors of apple phenolase (o-diphenol oxidase) and the associated biochemical defence system. But the problems of the initial establishment of fungal growth remain and I wish to report evidence that the fungus secretes its own phenolase inhibitor until it is sufficiently established to allow the second, major positive feedback system to take over.

Effect of pilocarpine on protein synthesis in the hamster submandibular gland.

Many histomorphological studies of the secretory cycle in salivary glands have been done (0. JARvI, Z Zellforsch 30:156-170, 1939; A. AMSTERDAM, I. OHAD, and M. SCHRAMM, J Cell Biol 41:753-773, 1969). However, little is known about concomitant rates of protein synthesis. Junqueira (Sekretion und Exkretion, Berlin: Springer-Verlag, 1965, p 31) has suggested that the synthetic phase of the secretary cycle is linked to the extrusion phase by a positive feedback system. The present investigation studied the effect of pilocarpine-induced secretion on protein synthesis in acinar and granular duct cells of the hamster submandibular gland. Young adult, male, golden Syrian hamsters (Cricetus auratus) were fasted for 48 hours but were allowed water ad libitum. Each of 23 hamsters received an intraperitoneal injection of 0.1 mg/100 gm body weight of pilocarpine hydrochloride in 1.0 ml of physiologic saline. Four control hamsters were given 1.0 ml of saline alone. At various intervals (Fig 1, 2) after injection, each animal received a single intravenous injection of 5 Rtc/gm body weight of L-leucine-4,5-3H in 0.01 N HCl.* All hamsters were killed 30 minutes after isotope injection, and the submandibular glands were fixed in Bouin-Hollande solution. Autoradiographs of 5 micrometer ([tm) sections were prepared using liquified NTB 2 emulsion.t Autoradiographs were analyzed, with the aid of an ocular reticle, by counting silver grains over the cytoplasm of each of 50 acinar and granular duct cells of similar size and shape. The statistical method of moving averages was used to describe all curves (J. P. GUILFORD, Fundamental Statistics, 1956). Studies have demonstrated that only a negligible amount of free or sonically bound radioactive leucine is retained in Bouin-fixed histologic sections after amino acid injection (B. DROZ and H. WARSHAWSKY, J Histochem Cytochem 11:426-435, 1963) and it is generaliy accepted that the radioactive particles recorded by the nuclear emulsion are emitted by labeled leucine molecules that have been incorporated into the structure of newly synthesized proteins. Pilocarpine produced an accelerated flow of saliva with no apparent changes in the gross or microanatomic appearance of the submandibular gland. The acinar and granular duct cells

Latency relationships between loosely coordinated locust flight motor neurons.

AbstractDuring flight the pattern of activity of the motor neurons of the locust wing muscles is normally a precisely controlled score. The elevator motor neurons are active in short synchronous impulse bursts and these alternate with similar bursts in the depressor motor neurons. In experimental preparations the normal coordination may break down, so that electrical stimulation of the nerve cord may elicit a very poorly coordinated response. In these cases, a histogram of the relative latencies of activity in two synergistic elevator motor neurons typically shows three modes, indicating that relative latency tends to assume values near 0 msec, about 6–8 msec, and about 25–35 msec. Simultaneous responses to common input play a major role in causing the peak at 0 msec. Excitatory synaptic interactions between motor neurons, or interneurons which drive them, appear to be responsible for the peak at 6–8 msec. The longest latency peak may be due to firing upon recovery from long‐term inhibitory interactions between the synergistic motor neurons. The short‐term excitatory feedback interactions between synergistic motor neurons probably are important for the production of the multiple firing in the impulse burst during flight. Long‐term inhibitory interactions may limit the activity in this positive feedback system and play a role in terminating each burst.

Alterations in LH and FSH content and weight of the anterior pituitary gland of immature female rats treated with PMS.

The pituitary content of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) was determined by quantitative bio-assay in glands removed during the afternoon of the day preceding PMS-induced ovulation in 27-day-old rats. It was found that no change in pituitary LH occurred between the hours of 2 and 7 pm, but that there was a 32% decrease in pituitary FSH. A significant decrease in pituitary LH was found when a comparison was made between the glandular content at 2 pm on the second and third days after PMS. An examination of pituitary weight in the PMS-treated rats showed a statistically significant hypertrophy during the afternoon of the day preceding ovulation. It was considered that this hypertrophy was due to estrogen stimulation and that ovarian estrogen is probably of primary importance in the positive feedback system which stimulates ovulating hormone (OH) release. (Endocrinology 80: 82, 1967)