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Entrainment, instability, quasi-periodicity, and chaos in a compound neural oscillator.

We studied the dynamical behavior of a class of compound central pattern generator (CPG) models consisting of a simple neural network oscillator driven by both constant and periodic inputs of varying amplitudes, frequencies, and phases. We focused on a specific oscillator composed of two mutually inhibiting types of neuron (inspiratory and expiratory neurons) that may be considered as a minimal model of the mammalian respiratory rhythm generator. The simulation results demonstrated how a simple CPG model--with a minimum number of neurons and mild nonlinearities--may reproduce a host of complex dynamical behaviors under various periodic inputs. In particular, the network oscillated spontaneously only when both neurons received adequate and proportionate constant excitations. In the presence of a periodic source, the spontaneous rhythm was overridden by an entrained oscillation of varying forms depending on the nature of the source. Stable entrained oscillations were inducible by two types of inputs: (1) anti-phase periodic inputs with alternating agonist-antagonist drives to both neurons and (2) a single periodic drive to only one of the neurons. In-phase inputs, which exert periodic drives of similar magnitude and phase relationships to both neurons, resulted in varying disruptions of the entrained oscillations including magnitude attenuation, harmonic and phase distortions, and quasi-periodic interference. In the absence of significant phasic feedback, chaotic motion developed only when the CPG was driven by multiple periodic inputs. Apneic episodes with repetitive alternation of active (intrinsic oscillation) and inactive (cessation of oscillation) states developed when the network was driven by a moderate periodic input of low frequency. Similar results were demonstrated in other, more complex oscillator models (that is, half-center oscillator and three-phase respiratory network model). These theoretical results may have important implications in elucidating the mechanisms of rhythmogenesis in the mature and developing respiratory CPG as well as other compound CPGs in mammalian and invertebrate nervous systems.

Animals↗

Perceptual interaction between carrier periodicity and amplitude modulation in broadband stimuli: a comparison of the autocorrelation and modulation-filterbank model.

Recent temporal models of pitch and amplitude modulation perception converge on a relatively realistic implementation of cochlear processing followed by a temporal analysis of periodicity. However, for modulation perception, a modulation filterbank is applied whereas for pitch perception, autocorrelation is applied. Considering the large overlap in pitch and modulation perception, this is not parsimonious. Two experiments are presented to investigate the interaction between carrier periodicity, which produces strong pitch sensations, and envelope periodicity using broadband stimuli. Results show that in the presence of carrier periodicity, detection of amplitude modulation is impaired throughout the tested range (8-1000 Hz). On the contrary, detection of carrier periodicity in the presence of an additional amplitude modulation is impaired only for very low frequencies below the pitch range (<33 Hz). Predictions of a generic implementation of a modulation-filterbank model and an autocorrelation model are compared to the data. Both models were too insensitive to high-frequency envelope or carrier periodicity and to infra-pitch carrier periodicity. Additionally, both models simulated modulation detection quite well but underestimated the detrimental effect of carrier periodicity on modulation detection. It is suggested that a hybrid model consisting of bandpass envelope filters with a ripple in their passband may provide a functionally successful and physiologically plausible basis for a unified model of auditory periodicity extraction.

Adult↗

Afferent synaptic transmission in a hair cell organ: pharmacological and physiological analysis of the role of the extended refractory period.

One feature of neuronal discharge proposed to play a role in coding temporal information is the relative refractory period that follows each action potential. In neurons innervating hair cells, there is an extended refractory period that can last </=100 ms. We have taken a pharmacological approach to examine the extended refractory period in the Xenopus lateral line organ. We show that each action potential in the afferent fiber, whether generated spontaneously or through an antidromic electrical pulse, decreases the probability of subsequent afferent discharge for a period of </=100 ms. We show that the extended refractory period can be modulated with drugs that alter glutamatergic transmission between the hair cell and the afferent fiber. The extended refractory period can be enhanced by perfusion with agents that reduce synaptic activity. These agents include blockers of voltage-dependent transmitter release, such as cobalt, as well as glutamate receptor antagonists, such as CNQX and kynurenic acid. Conversely, perfusion with agents that increase synaptic activity through activation of the glutamate receptors, such as AMPA or kainate, reduces the magnitude of suppression during the extended refractory period. The extended refractory period is greatly reduced by iberiotoxin and tetraethylammonium (TEA), indicating it may be mediated in large part by a calcium-dependent potassium channel. The ability to modulate the extended refractory period with changes in synaptic input suggests a simple, dynamic mechanism by which strong input (i.e., large or frequent excitatory postsynaptic potentials) can be strengthened and weak inputs weakened.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Periodic simple cells in cat area 17.

Quantitative, high-resolution static receptive-field plots (response planes) in cat area 17 revealed simple cells whose receptive fields were composed of four to six excitatory regions alternating in space with up to seven inhibitory regions. The size, shape, and spacing of the excitatory regions within these receptive fields were highly regular, giving the receptive field a periodic appearance in space. We call these periodic simple cells. A periodic simple cell's response to moving stimuli could, in general, be anticipated from the detailed spatiotemporal map of excitatory and inhibitory regions provided by response planes. This observation suggests that periodic simple cells, like the more common simple cells composed of one to three excitatory regions, sum spatially distributed inputs in a roughly linear manner. Based on a quantitative assessment of the spatial distribution and time course of response of single excitatory regions within periodic receptive fields, as described in the previous paper, we characterized periodic simple cells as either X-like or Y-like. Furthermore, we found that periodic simple cells classified as X-like gave a more sustained response to standing contrast and had significantly smaller excitatory regions than those cells classified as Y-like. Periodic simple cells were found in layer III and at the border between layers III and IVab. It is suggested that these cells, which reside outside the primary zone of geniculate termination and include both X-like and Y-like types, may be constructed hierarchically from the convergence of lower order simple cells. In the spatial-frequency domain, periodic simple receptive fields were predicted to have bandwidths at half-maximum ranging from 0.80 to 1.4 octaves. By comparison, the predicted bandwidths of cells composed of two or three excitatory regions ranged from 1.6 to 4.3 octaves. Thus as additional excitatory regions are added to the receptive fields of simple cells, their bandwidth narrows in the spatial-frequency domain.

Animals↗

Sequence periodicity of Escherichia coli is concentrated in intergenic regions.

BACKGROUND: Sequence periodicity with a period close to the DNA helical repeat is a very basic genomic property. This genomic feature was demonstrated for many prokaryotic genomes. The Escherichia coli sequences display the period close to 11 base pairs. RESULTS: Here we demonstrate that practically only ApA/TpT dinucleotides contribute to overall dinucleotide periodicity in Escherichia coli. The noncoding sequences reveal this periodicity much more prominently compared to protein-coding sequences. The sequence periodicity of ApC/GpT, ApT and GpC dinucleotides along the Escherichia coli K-12 is found to be located as well mainly within the intergenic regions. CONCLUSIONS: The observed concentration of the dinucleotide sequence periodicity in the intergenic regions of E. coli suggests that the periodicity is a typical property of prokaryotic intergenic regions. We suppose that this preferential distribution of dinucleotide periodicity serves many biological functions; first of all, the regulation of transcription.

Base Composition↗

An analysis of Wenkebach periodicity during atrial pacing.

Seventy-six atrial pacing induced Wenckebach periods in 20 patients were analyzed. They were divided into 5 types according to the manner of increment change of P'V prolongation. Fifty-four % of the periods were atypical (Types II-V). There was a significant increase in the incidence of atypical periods as the length of the periods increased. The recovery curve of the A-V node was obtained by plotting P'V against preceding VP'. The curve was convex and the slope became greater than 45 degrees near the absolute refractory period in the majority of the cases, although there was 1 case in which the slope was less than 45 degrees throughout the curve. The P'V interval was found to be determined mainly by the preceding VP' interval. The mechanism by which these different types of Wenckebach periods develop can be explained by the relationship between the shape of the recovery curve and the pacing rate. The types II, III, and IV periods which have been dealt with as atypical periods were understood to develop by the same mechanism as type I (typical) periods.

Adult↗

Effect of modified dry period lengths and bovine somatotropin on yield and composition of milk from dairy cows.

Dry periods of 40 to 60 d have been an industry standard because dry periods <40 d have resulted in reduced milk yields in the subsequent lactation by 10 to 30%. However, recent research has demonstrated no production losses for cows given a 30-d dry period. The current study evaluated milk production effects of shortened or omitted dry periods for cows at mature-equivalent production >12,000 kg of milk and treated with bovine somatotropin (bST). The study used 2 commercial dairies and one university dairy and included 4 treatments. Five multiparous and 5 primiparous cows from each farm were assigned to each treatment: 1) 60-d dry period, label use of bST (60DD); 2) 30-d dry period, label use of bST (30DD); 3) continuous milking, label use of bST (CMLST); and 4) continuous milking with continuous use of bST (CMCST). Per label, bST use started at 57 to 70 d in milk and ended 14 d before drying (60DD and 30DD) or expected calving date (CMLST). In primiparous cows, average milk yields during the first 17 wk of lactation were reduced for cows on treatments 30DD, CMLST, and CMCST vs. the 60DD treatment. (38.3, 35.1, and 37.5 vs. 44.1 +/- 1.3 kg/d, respectively). For multiparous cows, respective milk yields did not differ (46.6, 43.4, 46.5, and 47.7 +/- 2.1 kg/d). Shortened or omitted dry periods may impede mammary growth in primiparous cows, resulting in reduced milk yield in the subsequent lactation. In contrast, a shortened or omitted dry period with either bST protocol did not alter production in multiparous cows treated with bST. Quality aspects of prepartum milk and colostrum require additional characterization. For multiparous cows, milk income generated for short dry periods or for continuous milking might increase their profitability. At 17 wk of the subsequent lactation, estimates of the cumulative net margins of multiparous cows on the 30DD treatment and continuous milking treatments exceeded those of cows on the 60DD treatment by 40 dollars to 60 dollars per cow.

Animals↗

Periodicity and firing rate as candidate neural codes for the frequency of vibrotactile stimuli.

The flutter sensation is felt when mechanical vibrations between 5 and 50 Hz are applied to the skin. Neurons with rapidly adapting properties in the somatosensory system of primates are driven very effectively by periodic flutter stimuli; their evoked spike trains typically have a periodic structure with highly regular time differences between spikes. A long-standing conjecture is that, such periodic structure may underlie a subject's capacity to discriminate the frequencies of periodic vibrotactile stimuli and that, in primary somatosensory areas, stimulus frequency is encoded by the regular time intervals between evoked spikes, not by the mean rate at which these are fired. We examined this hypothesis by analyzing extracellular recordings from primary (S1) and secondary (S2) somatosensory cortices of awake monkeys performing a frequency discrimination task. We quantified stimulus-driven modulations in firing rate and in spike train periodicity, seeking to determine their relevance for frequency discrimination. We found that periodicity was extremely high in S1 but almost absent in S2. We also found that periodicity was enhanced when the stimuli were relevant for behavior. However, periodicity did not covary with psychophysical performance in single trials. On the other hand, rate modulations were similar in both areas, and with periodic and aperiodic stimuli, they were enhanced when stimuli were important for behavior, and were significantly correlated with psychophysical performance in single trials. Thus, the exquisitely timed, stimulus-driven spikes of primary somatosensory neurons may or may not contribute to the neural code for flutter frequency, but firing rate seems to be an important component of it.

Action Potentials↗

Short-period circumnutations found in sunflower hypocotyls in satellite orbit. A reappraisal of data from Spacelab-1.

We have further analysed data from an experiment performed in satellite orbit, in Spacelab-1. In micro-gravity the hypocotyls of Helianthus annuus, cv. "Teddy Bear", showed short period circumnutations (periods around 30 minutes) as well as the already reported long period nutations (with an average period of about 115 minutes). We applied various types of signal analysis (Fourier and wavelet analysis) to the data series. The long period circumnutations have a larger amplitude than the short term circumnutations. Both short and long period circumnutations exist in one and the same hypocotyl. (This is in contrast to our ground control experiments, where were found only the long-period nutations.) The period of the nutations changed throughout the experiment. These results are extending the conclusions drawn after the Spacelab experiment (Brown et al. 1990). In particular they emphasize the existence of both short- and long-period circumnutations in micro-gravity.

Fourier Analysis↗

Control of proliferation in mitogen responsive human peripheral blood lymphocytes: restimulation of cells stimulated by sodium periodate.

Human peripheral blood lymphocytes are stimulated to a greater extent by sodium periodate when cells are incubated in medium containing human serum than when incubated in medium with fetal calf serum. NaIO4 STIMULATION CAN BE REVERSED BY TREATMENT WITH SODIUM BOROHYDRIDE BUT CELLS ALREADY COMMITTED TO DIVISION ARE NOT AFFECTED BY BOROHYDRATE TREATMENT. Maximal commitment to DNA synthesis of a NaIO4 oxidized cell suspens-on occurs after about 28 hr of incubation in medium. The committal time after periodate stimulation is identical to that after stimulation with concanavalin A. Cells treated with periodate and then reduced with borohydride immediately after oxidation are refractory to further per-odate stimulation. Cells stimulated with periodate and then incubated for 6 hr before treatment with borohydride can be restimulated with periodate, indicating a turnover of membrane sites in the 6 hr period. Periodate-stimulated cells divide only once in response to the stimulation. The progeny of cells which were stimulated with periodate can be restimulated by treatment with either periodate or concanavalin A.

Animals↗

[Effect of pentagastrin on the periodic activity of gastroduodenal organs in dogs with intact and disrupted innervation of the stomach].

Chronic experiments on dogs with gastric and duodenal fistulas were made to study the effect of pentagastrin (6 micrograms/kg, s. c.) on the motor and secretory components of periodical activity of the gastroduodenal organs. Gastric secretion was collected from the open fistulas. To detect the role of the nervous mechanisms, subject to comparison were similar parameters of the periodic activity in 5 dogs with intact stomach innervation and in 6 dogs with preliminary circular gastrotomy in the upper third of the fundal part. Gastrotomy did not impair the periodical rhythm but led to the prolongation of the activity periods, decreased the contraction amplitude and shortened the periods of rest. The quantity of the periodical duodenal secretion was also diminished. In dogs with intact stomach innervation, pentagastrin inhibited the periodic contractions, stimulated the duodenum motility and caused an intensive special period of duodenal secretion. In disturbed innervation, these effects were less pronounced or completely disappeared. It is concluded that central parasympathetic innervation plays an important role in he mechanism of the pentagastrin effect on the periodic activity of the gastroduodenal organs.

Animals↗

Citation characteristics of periodical literature in veterinary science.

The usage of periodical literature in veterinary science was measured by means of citation analysis. Eighty-two percent of the citations in the source of this study, Advances in Veterinary Science and Comparative Medicine (1970-1974), were from periodicals, and 70 of the 743 periodical titles cited (9.4%) contributed 66% of the total periodical citations. Periodical literature cited in the source of the study appeared to have a half-life of 6.1 years, and to double its size approximately every 20 years. The aging patterns of the periodical literature seemed to vary with the publishing age of the periodical, i.e., the literature in the periodicals which have been in publication for more than 40 years showed a more gradual aging pattern than did that in the newer periodicals.

Periodicals as Topic↗

[Current status of clinical and molecular-biological research on familial periodic paralysis].

Types of periodic paralysis seen in Japan are numerous: the one most frequently seen is hypokalemic periodic paralysis. Among them, approximately 50% are secondary to thyrotoxicosis. Number of families of familial hyperkalemic periodic paralysis have also been reported so far. Several cases of hyperkalemic periodic paralysis secondary to thyrotoxicosis have also been reported exclusively from Japan. As the pathogenesis of hypokalemic periodic paralysis, depolarization block induced by membrane permeability change in the face of hypokalemia triggered by excess insulin was strongly suggested and supported experimentally in part. Recent linkage analysis on familial hypokalemic periodic paralysis revealed that the abnormality is linked to a mutation in voltage-gated Ca channel. The difficulty remains how to explain the cause of hypokalemia which is almost always preceding the attack of periodic paralysis of this type. The cause of hyperkalemic periodic paralysis was shown to be the mutation in voltage-gated Na channel. Failure of inactivation of the channel causes an increase in inward sodium current which results in depolarization and accumulation of potassium. The explanation of the pathogenesis of paralysis is straight-forward when compared to that of hypokalemic periodic paralysis.

Calcium Channels↗

Run-in periods in randomized trials: implications for the application of results in clinical practice.

Prerandomization run-in periods are being used to select or exclude patients in an increasing number of clinical trials, but the implications of run-in periods for interpreting the results of clinical trials and applying these results in clinical practice have not been systematically examined. We analyzed illustrative examples of reports of clinical trials in which run-in periods were used to exclude noncompliant subjects, placebo responders, or subjects who could not tolerate or did not respond to active drug. The Physicians' Health Study exemplifies the use of a prerandomization run-in period to exclude subjects who are nonadherent, while recent trials of tacrine for Alzheimer disease and carvedilol for congestive heart failure typify the use of run-in periods to exclude patients who do not tolerate or do not respond to the study drug. The reported results of these studies are valid. However, because the reported results apply to subgroups of patients who cannot be defined readily based on demographic or clinical characteristics, the applicability of the results in clinical practice is diluted. Compared with results that would have been observed without the run-in period, the reported results overestimate the benefits and underestimate the risks of treatment, underestimate the number needed to treat, and yield a smaller P value. The Cardiac Arrhythmia Suppression Trial exemplifies the use of an active-drug run-in period that enhances clinical applicability by selecting a group of study subjects who closely resembled patients undergoing active clinical management for this problem. Run-in periods can dilute or enhance the clinical applicability of the results of a clinical trial, depending on the patient group to whom the results will be applied. Reports of clinical trials using run-in periods should indicate how this aspect of their design affects the application of the results to clinical practice.

Clinical Protocols↗

The changing trends of uterine cancer and cytology: a study of morbidity and mortality trends over a twenty year period.

Data on squamous carcinoma of the cervix from a 20 year study period (1955 to 1974) in metropolitan Toledo revealed a 66% reduction of the average annual age-adjusted incidence rate and a 61% reduction in death rate of cervical squamous carcinoma when the first time period (1955 to 1958) was compared with the last time period (1971 to 1974). The decrease for both morbidity and mortality rates was more pronounced in women age 50 years and younger. The age-adjusted death rate during this study period revealed 15.5/100,000 for black women and 8.7/100,000 for white women. The reduction in death rate of 83% in black women is more prominent than 54.5% in white women. The decrease in both morbidity and mortality for cervical squamous carcinoma has a close relation to cytologic screening activity. The factors of age and race, probably related to socioeconomic status, are two known determinants of risk for cervical squamous carcinoma. Data for endometrial carcinoma during this study period revealed 15.5/100,000 women in the average age-adjusted incidence and an increase of 13.8% in average yearly rates when the first time period (1955 to 1958) were compared with the last time period (1971 to 1974). The peak age was 60 to 64 years old in the first time period and shifted to 70 to 74 years old in the last time period. The trend in metropolitan Toledo is comparable to that of Louisville, Kentucky. The mass cytologic screening program which contributed to a remarkable reduction in morbidity and mortality for the cervical squamous carcinoma, did not have any beneficial effect on endometrial carcinoma.

Adult↗

A periodic cytoskeletal lattice in striated muscle.

The axial periodicities of electron density in striated muscle fibers extend over four orders of magnitude, ranging from the sarcomere repeat (2000-3000 nm) to a residue repeat in the alpha-helix of structural proteins (0.15 nm). A prevailing idea about the regular arrangement of structures in the contractile apparatus maintains that long-range axial spacings, related to the organization of sarcomere repeats, are essentially independent of the short-range periodicities with molecular dimensions. This is a central theme of the sliding filament hypothesis but is only supported by evidence from measured spacings near the upper and lower limits in the spectrum of dimensions, leaving a wide gap in resolved structural information extending from about 460 down to 50 nm. Several independent morphological methods show an electron-dense cross-striation of low amplitude with a pseudo-period of 230 nm, out of phase with the sarcomere repeat, in myofibrils of frog twitch fibers. Averaged images of embedded muscle fibers indicate that the sarcomere repeat contains five symmetrical pairs of these striations, which are coordinated with discrete repeats of the major molecular periods in the thick and thin filaments, in register within A and I bands. The pseudo-period therefore correlates short-range molecular repeats in the filaments with long-range registry of the sarcomere repeats in myofibrils. This raises the interesting possibility that the 230-nm pseudo-periodicity identifies a replicated axial structure in myofibrils that integrates the organization of the major structural proteins into the sarcomere repeat. The density distribution in sarcomeres of isolated unstained myofibrils also establishes that symmetrical pairs of striations with intrinsically low amplitudes are independently distorted out of uniform register in stretched sarcomeres. This behavior is consistent with the properties of N lines. The out-of-phase arrangement of 230-nm striations in the sarcomere repeat of twitch fibers should produce special diffraction effects in the region of the gap in the spectrum of periodicities recorded from muscle, with maxima at spacings extending from 200 to 80 nm. Correspondence between the diffraction spectrum of myofibril models containing a 230-nm spaced axial pseudo-period and the observed very low-angle X-ray diffraction spacings from living muscle (Huxley and Brown, 1967) suggests that the 230-nm pseudo-periodicity is a regular detectable component of striated muscle, resembling the structure of naturally occurring leptomeric fibrils in extrafusal and intrafusal fibers (Karlson and Andersson-Cedergren, 1968).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Postnatal methylmercury exposure induces hyperlocomotor activity and cerebellar oxidative stress in mice: dependence on the neurodevelopmental period.

During the early postnatal period the central nervous system (CNS) is extremely sensitive to external agents. The present study aims at the investigation of critical phases where methylmercury (MeHg) induces cerebellar toxicity during the suckling period in mice. Animals were treated with daily subcutaneous injections of MeHg (7 mg/kg of body weight) during four different periods (5 days each) at the early postnatal period: postnatal day (PND) 1-5, PND 6-10, PND 11-15, or PND 16-20. A control group was treated with daily subcutaneous injections of a 150 mM NaCl solution (10 ml/kg of body weight). Subjects exposed to MeHg at different postnatal periods were littermate. At PND 35, behavioral tests were performed to evaluate spontaneous locomotor activity in the open field and motor performance in the rotarod task. Biochemical parameters related to oxidative stress (levels of glutathione and thiobarbituric acid reactive substances, as well as glutathione peroxidase and glutathione reductase activity) were evaluated in cerebellum. Hyperlocomotor activity and high levels of cerebellar thiobarbituric acid reactive substances were observed in animals exposed to MeHg during the PND 11-15 or PND 16-20 periods. Cerebellar glutathione reductase activity decreased in MeHg-exposed animals. Cerebellar glutathione peroxidase activity was also decreased after MeHg exposure and the lowest enzymatic activity was found in animals exposed to MeHg during the later days of the suckling period. In addition, low levels of cerebellar glutathione were found in animals exposed to MeHg during the PND 16-20 period. The present results show that the postnatal exposure to MeHg during the second half of the suckling period causes hyperlocomotor activity in mice and point to this phase as a critical developmental stage where mouse cerebellum is a vulnerable target for the neurotoxic and pro-oxidative effects of MeHg.

Animals↗

Regional myocardial function after repetitive brief episodes of ischemia: effect of altering the duration of the reperfusion period.

How recovery of regional contractile function in myocardium is influenced by alterations in the duration of reperfusion after repetitive brief coronary artery occlusions was investigated in chronically instrumented, conscious dogs. All animals underwent five 5 minute left anterior descending coronary artery occlusions with a final 5-hour reperfusion period. Dogs were randomly assigned to one of three groups determined by the duration of reperfusion (5, 10, or 15 minutes) between successive 5-minute occlusion periods. A shortening of the duration of the reperfusion period between occlusions led to reduced recovery and progressive deterioration in systolic shortening after multiple occlusion-reperfusion sequences. With 15-minute reperfusion periods, the percentage of segment shortening (%SS) during the first through fourth reperfusion periods ranged from 17.1 +/- 2.6% to 18.2 +/- 1.8% and did not differ from the preocclusion control value (18.8 +/- 1.7%) by the end of the final reperfusion period. In contrast, in those dogs with 5-minute reperfusion periods, %SS was significantly reduced from the preocclusion control value (20.2 +/- 2.2%) at the completion of the final 5-hour reperfusion period (11.4 +/- 1.5%). Results of the present study indicate that after only a few brief periods of coronary artery occlusion, rapid and cumulative deterioration in regional contractile function can occur when the duration of intermittent reperfusion is sufficiently brief.

Animals↗