Motoneurons are altered in muscular dystrophy.

The activity of motoneurons supplying the brachial biceps muscle was examined in eight control subjects and 26 patients affected by Duchenne muscular dystrophy. The patients were subdivided into two groups: one whose motor units (MU) fired with normal rates (N group) and the other whose MU firing rates were higher as compared to controls (I group). Firing rates of motoneurons of patients from group I increased more rapidly with increasing force level. The relationship between the standard deviation of interspike intervals and their mean value, sigma(Tm), was shifted towards the shorter intervals and lower standard deviations in both groups of patients. The numerical values describing these changes correlated with the severity of disease. The MU recruitment was comparable for control subjects and for patients. Experimental results as well as computer simulations indicate that the break-point of the function sigma(Tm) is correlated with motoneuronal properties, and in particular with the afterhyperpolarization (AHP) duration. In muscular dystrophy this break-point corresponds to the shorter interspike intervals. Therefore, we propose that the motoneurons in muscular dystrophy are altered either in response to the muscle degeneration or as a result of the disease itself.     

Mapping somatosensory evoked potentials to finger stimulation at intervals of 450 to 4000 msec and the issue of habituation when assessing early cognitive components

Somatosensory evoked potentials (SEPs) to mild electric stimulation of two fingers of the left hand were studied at regular interstimulus intervals (ISIs) of 450, 800, 1400, 2500 and 4000 msec. Habituation was evaluated while the subject was reading a novel so as to virtually ignore the finger stimuli while maintaining steady vigilance levels. Brain SEPs recorded from 25 scalp electrodes were assessed by scatter displays, electronic subtraction, bit-mapped potentials fields, and by calculating theZ estimator and dilation factor. Similar results were obtained with randomly varying ISIs. The P14 farfield and cortical N20 did not change with ISIs. The parietal P27–P45 decreased at ISIs of 800 and 450 msec, but showed no significant habituation at ISIs of 1400, 2500 or 4000 msec. This validated the control conditions used for assessing the early cognitive P30 and P40 to attended target stimuli. The frontal N30 also decremented at the shorter ISIs but still habituated up to ISIs of 2500 msec. The clear dissociation between frontal N30 and parietal P27 at the larger ISIs suggests that they involve at least in part distinct neural generators.     

Influence of different resistance exercise loading schemes on mechanical power output in work to rest ratio - equated and - nonequated conditions

It is well known that most sports are characterized by the performance of intermittent high-intensity actions, requiring high muscle power production within different intervals. In fact, the manipulation of the exercise to rest ratio in muscle power training programs may constitute an interesting strategy when considering the specific performance demand of a given sport modality. Thus, the aim of this study was to evaluate the influence of different schemes of rest intervals and number of repetitions per set on muscle power production in the squat exercise between exercise to rest ratio-equated and -nonequated conditions. Nineteen young males (age: 25.7 ± 4.4 years; weight: 81.3 ± 13.7 kg; height: 178.1 ± 5.5 cm) were randomly submitted to 3 different resistance exercise loading schemes, as follows: short-set short-interval condition (SSSI; 12 sets of 3 repetitions with a 27.3-second interval between sets); short-set long-interval condition (SSLI; 12 sets of 3 repetitions with a 60-second interval between sets); long-set long-interval (LSLI; 6 sets of 6 repetitions with a 60-second rest interval between sets). The main finding of the present study is that the lower exercise to rest ratio protocol (SSLI) resulted in greater average power production (601.88 ± 142.48 W) when compared with both SSSI and LSLI (581.86 ± 113.18 W; 578 ± 138.78 W, respectively). Additionally, both the exercise to rest ratio-equated conditions presented similar performance and metabolic results. In summary, these findings suggest that shorter rest intervals may fully restore the individual's ability to produce muscle power if a smaller exercise volume per set is performed and that lower exercise to rest ratio protocols result in greater average power production when compared with higher ratio ones.     

Temporal encoding in a nervous system

We examined the extent to which temporal encoding may be implemented by single neurons in the cercal sensory system of the house cricket Acheta domesticus. We found that these neurons exhibit a greater-than-expected coding capacity, due in part to an increased precision in brief patterns of action potentials. We developed linear and non-linear models for decoding the activity of these neurons. We found that the stimuli associated with short-interval patterns of spikes (ISIs of 8 ms or less) could be predicted better by second-order models as compared to linear models. Finally, we characterized the difference between these linear and second-order models in a low-dimensional subspace, and showed that modification of the linear models along only a few dimensions improved their predictive power to parity with the second order models. Together these results show that single neurons are capable of using temporal patterns of spikes as fundamental symbols in their neural code, and that they communicate specific stimulus distributions to subsequent neural structures.     

Thermal denaturation profiles of deoxypolynucleotide-ligand complexes: semiempirical studies

We have semiempirically studied the thermal denaturation profiles of complexes formed between double strand polynucleotides and pure stabilizer nonspecific binding ligands. By using the McGhee model (J. D. McGhee, (1976) Biopolymers 15, 1345-1375) we have found a simple, analytical relationship between the melting temperature (Tm) and the Kh (intrinsic association constant), nh (apparent site size), and wh (cooperativity constant) values of the interaction. The validity of this approach strongly depends on the sigma value (sigma being the nucleation parameter of the DNA). Through the equation so obtained it is possible to calculate the Kh, nh, and wh values from the melting temperature of three experimental thermal denaturation profiles at different r (ligand/polynucleotide ratio) values. The method has been checked by studying the thermal denaturation profiles of daunomycin-poly(d(A-T)).poly(d(A-T)) complexes in two different salt concentrations. The results so obtained are compared with those previously described using other techniques. The applicability of the method here developed is discussed in relation with both the nature of the ligands and the value of the nucleation parameter (sigma).     

Influence of cis double bonds in the sn-2 acyl chain of phosphatidylethanolamine on the gel-to-liquid crystalline phase transition.

We have semisynthesized 19 species of mixed-chain phosphatidylethanolamines (PEs) in which the sn-1 acyl chain is derived from saturated fatty acids with varying chain lengths and the sn-2 acyl chain has different chain lengths but contains 0, 1, and 2 cis double bond(s). The gel-to-liquid crystalline phase transition temperatures (Tm) of lipid bilayers prepared from these 19 mixed-chain PEs were determined calorimetrically. When the Tm values are compared with those of saturated and monounsaturated counterparts, a common Tm profile is observed in the plot of Tm versus the number of cis double bonds. Specifically, a marked stepwise decrease in Tm is detected as the number of cis double bonds in the sn-2 acyl chain of the mixed-chain PE is successively increased from 0 to 1 and then to 2. The large Tm-lowering effect of the acyl chain unsaturation can be attributed to the increase in Gibbs free energy of the gel-state bilayer as a result of weaker lateral chain-chain interactions. In addition, we have applied molecular mechanics calculations to simulate the molecular structure of dienoic mixed-chain C(X):C(Y:2 delta n,n+3)PE in the gel-state bilayer, thus enabling the three independent structural parameters (N, delta C, and LS) to be calculated in terms of X, Y, and n, which are intrinsic quantities of C(X):C(Y:2 delta n,n+3)PE. When the Tm values and the corresponding N and delta C values of all dienoic mixed-chain PEs under study are first codified and then analyzed statistically by multiple regressions, the dependence of Tm on the structural parameters can be described quantitatively by a simple and general equation. The physical meaning and the usefulness of this simple and general equation are explained.     

体感皮层神经元放电间隔的概率密度函数与分布参数

本文建立了估计ISI概率密度函数的标准化ISI直方图和分布参数拟合方法,对34例猫体感皮层神经元自发和诱发放电活动进行了统计分析.     

Parameters for a model of an oscillating neuronal network in the cochlear nucleus defined by genetic algorithms

Chopper neurons in the cochlear nucleus are characterized by intrinsic oscillations with short average interspike intervals (ISIs) and relative level independence of their response (Pfeiffer, Exp Brain Res 1:220–235, 1966; Blackburn and Sachs, J Neurophysiol 62:1303–1329, 1989), properties which are unattained by models of single chopper neurons (e.g., Rothman and Manis, J Neurophysiol 89:3070–3082, 2003a). In order to achieve short ISIs, we optimized the time constants of Rothman and Manis single neuron model with genetic algorithms. Some parameters in the optimization, such as the temperature and the capacity of the cell, turned out to be crucial for the required acceleration of their response. In order to achieve the relative level independence, we have simulated an interconnected network consisting of Rothman and Manis neurons. The results indicate that by stabilization of intrinsic oscillations, it is possible to simulate the physiologically observed level independence of ISIs. As previously reviewed and demonstrated (Bahmer and Langner, Biol Cybern 95:371–379, 2006a), chopper neurons show a preference for ISIs which are multiples of 0.4 ms. It was also demonstrated that the network consisting of two optimized Rothman and Manis neurons which activate each other with synaptic delays of 0.4 ms shows a preference for ISIs of 0.8 ms. Oscillations with various multiples of 0.4 ms as ISIs may be derived from neurons in a more complex network that is activated by simultaneous input of an onset neuron and several auditory nerve fibers.     

Conformation and interaction of short nucleic acid double-stranded helices. I. Proton magnetic resonance studies on the nonexchangeable protons of ribosyl ApApGpCpUpU.

1H nuclear magnetic resonance (NMR) spectra of a self-complementary ribosyl hexanucleotide, A2GCU2, are investigated as a function of temperature and ionic strength in D2O. Seventeen nonexchangeable base and ribose-H1' resonances are resolved, and unequivocally assigned by a systematic comparison with the spectra of a series of oligonucleotide fragments of the A2GCU2 sequence varying in chain length from 2 to 5. Changes in the chemical shifts of the 17 protons from the hexamer as well as the six H1'-H2' coupling constants are followed throughout a thermally induced helix-coil transition. These sigma vs. T and J vs. T (degrees C) profiles indicate that the transition is not totally cooperative and that substantial populations of partially bonded structures must exist at intermediate temperatures, with the central G-C region being most stable. Transitions in chemical shift for protons in the same base pair exhibit considerable differences in their Tm values as the data reflect both thermodynamic and local magnetic field effects in the structural transition, which are not readily separable. However, an average of the Tm values agrees well with the value predicted from studies of the thermally induced transition made by optical methods. The values of J1'-2' for all six residues become very small (less than 1.5 Hz) at low temperatures indicating that C3'-endo is the most heavily populated furanose conformation in the helix. The sigma values of protons in the duplex were compared with those calculated from the ring current magnetic anisotropies of nearest and next-nearest neighboring bases using the geometrical parameters of the A'-RNA and B-DNA models. The sigma values of the base protons in the duplex calculated assuming the A'-RNA geometry agree (+/- approximately 0.1 ppm) with the observed values much more accurately than those calculated on the basis of B-DNA geometry. The measured sigma values of the H1' are not accurately predicted from either model. The synthesis of 35 mg of A2GCU2 using primer-dependent polynucleotide phosphorylase is described in detail with extensive discussion in the microfilm edition.     

The effect of interstimulus interval on somatosensory point localization

Somatosensory point localization is a clinical test evaluating spatial accuracy of the somatosensory system. Possible effects of the interstimulus interval (ISI) on point localization threshold have not been previously examined. In the present set of experiments the effect of time delay on somatosensory point localization was studied using ISIs of 1, 3, 5, 7, and 9 s, and applying a newly developed computer-controlled application method of a Semmes-Weinstein monofilament. It was found that the point localization threshold was not significantly affected by the ISI length. However, the response time was shorter and response accuracy better at the shorter (1 and 3 s) than at the longer (5, 7, and 9 s) ISIs, suggesting a change in the mechanism underlying point localization decision criteria in ISIs longer than 3 s.     

The dependence of simple reaction time on temporal patterns of stimuli

Simple reaction time has been measured using various distributions of interstimulus intervals (ISIs), which differed both in the shape of their envelope and in their degree of discretization. For each of 7 such conditions, and for three mean ISIs (2.0, 3.3, and 5.8 s) 600 responses of two subjects have been accumulated.Reaction times depend significantly on the shape of ISI-distributions but also on their degree of discretization. Within an experimental run they depend on single ISIs back to the third before reaction, and on sequences of ISIs. The latter effects are again influenced by the discretization of ISIs. Finally it was found that some learning of the distribution pattern (not the mere mean value) of ISIs takes place.Our results shed some light on existing hypotheses of RT. Some inconsistencies of earlier experimental results can probably be explained by insufficient consideration of the discretization and the learning effects.     

Detection of deterministic behavior within the tissue injury-induced persistent firing of nociceptive neurons in the dorsal horn of the rat spinal cord

To unravel the temporal features of the peripheral tissue injury induced persistent nociceptive discharge, single wide dynamic range (WDR) unit activity was recorded extracellularly in lumbar dorsal horn of anesthetized rats and interspike interval (ISI) series were obtained. Subcutaneous (s.c.) bee venom (BV) injection induced persistent discharge of spinal WDR neurons and has been well established to be a good model in evaluation of tissue injury induced pain. By applying a more novel approach, i.e., the unstable periodic orbit (UPO) identification method, we detected a family of significant separate UPOs (period-1, 2 and 3 orbits) within the ISI series of BV-induced nociceptive discharge, but not spontaneous background activity of spinal WDR neuron. Furthermore, temporally dynamic changes of UPOs at lower period-1, 2 and 3 for 4 successive time segments within 1 h time course of WDR unit firing showed temporally dynamic changes, i.e., new orbits with longer ISIs emerged and those with shorter ISIs vanished with time change. By using this method we suggest that BV-induced nociceptive discharge of spinal WDR neuron be a kind of deterministic activity and various UPOs may play some role in temporal coding of sensory information.     

Effect of sodium octanoate and sodium perfluorooctanoate on gel-to-liquid-crystalline phase transition of dipalmitoylphosphatidylcholine vesicle membrane

The gel-to-liquid-crystalline phase transition of dipalmitoylphosphatidylcholine (DPPC) vesicle membrane was measured in the presence of sodium octanoate (SO) (pH 3 and 10) and sodium perfluorooctanoate (SPFO) (pH uncontrolled) by monitoring the scattered light intensity of the vesicle suspension. The phase transition temperature, Tm, decreased linearly with the concentration of added SO within the measured concentration range; the uncharged form of SO (pH 3) was much more effective for the depression of Tm than the charged form (pH 10). On the other hand, with increasing SPFO concentration, levelling off of Tm was observed after depression at an initial stage. From the depression of Tm, the partition coefficients, K, of these surfactants between bulk solution and DPPC vesicle membrane were estimated and compared with those obtained previously for other surfactant systems. The value of K for charged SO fell on the straight line of log K vs. Nc plot for anionic surfactants, where Nc is the carbon number of the hydrocarbon chain of surfactants, whereas K for uncharged SO showed a large positive deviation from the straight line of the plot for non-ionic surfactants. The latter suggested that some specific interaction, presumably hydrogen bond formation, may act between the protonated carboxyl group of SO and the lipid head group. The K value estimated for SPFO was much larger than that for charged SO. This difference in the affinity for the lipid bilayer between fluorocarbon surfactant and hydrocarbon surfactant may be attributed to the difference in their hydrophobicity.     

Deglutitive inhibition affects both esophageal peristaltic amplitude and shortening

Deglutitive inhibition attenuates ongoing esophageal contractions if swallows are separated by short time intervals. This study aimed to determine whether esophageal shortening, mediated by longitudinal muscle, was similarly affected. Eight healthy subjects with two distal esophageal segments demarcated by mucosal clips and manometric recording sites positioned within those segments underwent concurrent manometry and fluoroscopy. Peristaltic amplitude and change in distal segment lengths were quantified during single swallows, paired swallows separated by progressively prolonged intervals, and a series of rapid repetitive swallows. During grouped swallows, deglutitive inhibition with complete attenuation of both the manometric contraction and segment shortening was evident with short-interval swallows and rapid-sequence swallows. No inhibition of either was evident with long-interval pairs. With intermediate interswallow intervals, the occurrence and degree of deglutitive inhibition between peristaltic amplitude and segment shortening were closely correlated. Deglutitive inhibition affects both the longitudinal and circular muscle layers of the esophageal wall, and the occurrence of inhibition evident in one layer is strongly correlated with the other.     

The 3-Second Rule in Hereditary Pure Cerebellar Ataxia: A Synchronized Tapping Study

The ‘3-second rule’ has been proposed based on miscellaneous observations that a time period of around 3 seconds constitutes the fundamental unit of time related to the neuro-cognitive machinery in normal humans. The aim of paper was to investigate the temporal processing in patients with spinocerebellar ataxia type 6 (SCA6) and SCA31, pure cerebellar types of spinocerebellar degeneration, using a synchronized tapping task. Seventeen SCA patients (11 SCA6, 6 SCA31) and 17 normal age-matched volunteers participated. The task required subjects to tap a keyboard in synchrony with sequences of auditory stimuli presented at fixed interstimulus intervals (ISIs) between 200 and 4800 ms. In this task, the subjects required non-motor components to estimate the time of forthcoming tone in addition to motor components to tap. Normal subjects synchronized their taps to the presented tones at shorter ISIs, whereas as the ISI became longer, the normal subjects displayed greater latency between the tone and the tapping (transition zone). After the transition zone, normal subjects pressed the button delayed relative to the tone. On the other hand, SCA patients could not synchronize their tapping with the tone even at shorter ISIs, although they pressed the button delayed relative to the tone earlier than normal subjects did. The earliest time of delayed tapping appearance after the transition zone was 4800 ms in normal subjects but 1800 ms in SCA patients. The span of temporal integration in SCA patients is shortened compared to that in normal subjects. This could represent non-motor cerebellar dysfunction in SCA patients.     

Stacking energies in DNA

Variations in base mono- and dipoles result in variations in stacking energies for the 10 unique neighbor pairs in DNA. Stacking energies for pair M on N, expressed as TMN, were derived by matrix decomposition of a large set of linear algebraic expressions relating the measured Tm for subtransitions emanating from large polymeric DNAs, and the fractional neighbor frequencies, fMN, for the domains responsible for the transitions, Tm = sigma fMNTMN. Tm were determined for subtransitions that dissociate in approximately all-or-none fashion in high resolution melting profiles of partially deleted and recombinant forms of pBR322 DNA. Three different analytical maneuvers were undertaken to resolve subtransitions: site-specific cleavage of domains; deletion of domains; and addition of domains. Three dozen domains of widely divergent, quasi-random neighbor frequencies were identified and assigned, resulting in a unique set of values for TMN with standard deviation, sigma = +/- 0.23 degree C. The average difference between calculated and experimental Tm for domains is only +/- 0.17 degree C, indicating that the thermodynamic properties of these domains are not in any way unusual. Assuming delta S to be constant for all pairs, the corresponding delta HMN are found to have a precision of +/- 10 calories.mol-1 and an accuracy of +/- 606 calories.mol-1. TMN used to calculate melting curves by statistical mechanical analysis of sequences of the different plasmid specimens in this study were in quantitative agreement with observed curves for most sequences. These TMN differ significantly from those determined previously and also correlate poorly with values determined by quantum chemical analysis. Stabilities of neighbor pairs, expressed as the difference in free energy between that for a given pair (MN) and that for the average of like pairs (M, N), depend on the relationship of stacked purines and pyrimidines as follows. delta delta Gpu-py(-466 cal) greater than delta delta Gpu-pu(+52 cal) greater than delta delta Gpy-pu(+335 cal) Differences between experimental Tm and Tm calculated with TMN for the isolated neighbor pairs in the B-conformation are useful in the identification of altered structures and unusual modes of dissociation of helixes. A significantly higher Tm is observed for the highly biased repeated sequence synthetic helixes dA.dT, d(AGC).d(GCT), and d(GAT).d(ATC), reflecting auxiliary sources of stability such as bifurcated hydrogen bonds and/or altered structures for these helixes.     

Intense synaptic activity enhances temporal resolution in spinal motoneurons

In neurons, spike timing is determined by integration of synaptic potentials in delicate concert with intrinsic properties. Although the integration time is functionally crucial, it remains elusive during network activity. While mechanisms of rapid processing are well documented in sensory systems, agility in motor systems has received little attention. Here we analyze how intense synaptic activity affects integration time in spinal motoneurons during functional motor activity and report a 10-fold decrease. As a result, action potentials can only be predicted from the membrane potential within 10 ms of their occurrence and detected for less than 10 ms after their occurrence. Being shorter than the average inter-spike interval, the AHP has little effect on integration time and spike timing, which instead is entirely determined by fluctuations in membrane potential caused by the barrage of inhibitory and excitatory synaptic activity. By shortening the effective integration time, this intense synaptic input may serve to facilitate the generation of rapid changes in movements.     

Alpha-helix to random-coil transitions of two-chain coiled coils: the use of physical models in treating thermal denaturation equilibria of isolated subsequences of alpha alpha-tropomyosin

Two extant models of thermal folding/unfolding equilibria in two-chain, alpha-helical coiled coils are tested by comparison with experimental results on excised, isolated subsequences of rabbit alpha alpha-tropomyosin (Tm). These substances are designated iTmj where i and j are, respectively, the residue numbers (in the 284-residue parent chain) of the N- and C-terminal residues of the subsequence. One model postulates that a coiled coil consists of segments, each denaturing in an all-or-none manner, like small globular proteins. Thus this model yields a small number of populated molecular species. In an extant calorimetry study of 11Tm127 and of 190Tm284, each required only two all-or-none-segments, and their enthalpies and transition temperatures were assigned. These assignments are shown here to yield the concentration of all molecular species, and therefore the helix content, as a function of temperature. Such calculations for 190Tm284 are in tolerable agreement with CD experiments, but those for 11Tm127 are in gross disagreement. Thus, either the model itself or the calorimetric assignment is faculty. In the second model, all conformational states are counted and weighted, as in the Zimm-Bragg theory for single-chain polypeptides. This theory has been extended (by Skolnick) to two-chain coiled coils and is here used to fit CD data for 11Tm127, 142Tm281, and 190Tm284. The fit is tolerable for 11Tm127, good for 142Tm281, and quantitative for 190Tm284. Thus this comparison does not falsify this second model. The helix-helix interaction free energy, obtainable from the fit, shows nonadditivity when isolated subsequences are compared with the parent. This suggests that removal of a region from a long coiled coil allows energetically substantial adjustments in side-chain packing in the helix-helix interface. Thus, the helix-helix interaction in long coiled coils is characteristic of a global free energy minimum and not just of the regional constellation of side chains.     

The anatomy of the interventricular septum of the heart and the anatomical nomenclature

With the aim to study interrelations of the interventricular septum (IVS) and systematization of their definitions, 151 preparations of hearts of persons died from causes having no connections with cardio-vascular diseases have been studied. The IVS consists of inflow and outflow septa. The inflow septum includes the sinusal (posterior) and trabecular septa, the outflow one--the anterior and conoid septa. The distal part of the anterior and conoid septa form the infundibular septum. From the side of the right ventricle the conoid septum and bulboventricular fold form a supraventricular crest--muscular torus, separating its inflow and outflow parts. From the side of the left ventricle the supraventricular crest is seen as a muscular bar, forming the basal medial wall.