Interhemispheric asymmetry of the spatial organization of human cortical potentials during the perception of emotional and indifferent images

In 13 healthy subjects dynamic characteristics of potentials spatial-temporal organization (PSTO) in the cortical left and right hemispheres at presentation of emotionally coloured and indifferent graphic images were studied by the method of quantitative evaluation of subsequent electroencephalotopograms. It is shown that, in contrast to the state of calm alertness, presentation of emotional and indifferent images leads to a decrease of the time of discordance in the hemispheres activity i.e. to synchronization increase. At the action of emotionally coloured images differences were found between the reorganizations of the left and right hemispheres, while there were no such differences at the presentation of indifferent images.     

Effect of water deprivation on cognitive-motor performance in healthy men and women

Whether mental performance is affected by slowly progressive moderate dehydration induced by water deprivation has not been examined previously. Therefore, objective and subjective cognitive-motor function was examined in 16 volunteers (8 females, 8 males, mean age: 26 yr) twice, once after 24 h of water deprivation and once during normal water intake (randomized cross-over design; 7-day interval). Water deprivation resulted in a 2.6% decrease in body weight. Neither cognitive-motor function estimated by a paced auditory serial addition task, an adaptive 5-choice reaction time test, a manual tracking test, and a Stroop word-color conflict test nor neurophysiological function assessed by auditory event-related potentials P300 (oddball paradigm) differed (P > 0.1) between the water deprivation and the control study. However, subjective ratings of mental performance changed significantly toward increased tiredness (+1.0 points) and reduced alertness (-0.9 points on a 5-point scale; both: P < 0.05), and higher levels of perceived effort (+27 mm) and concentration (+28 mm on a 100-mm scale; both: P < 0.05) necessary for test accomplishment during dehydration. Several reaction time-based responses revealed significant interactions between gender and dehydration, with prolonged reaction time in women but shortened in men after water deprivation (Stroop word-color conflict test, reaction time in women: +26 ms, in men: -36 ms, P < 0.01; paced auditory serial addition task, reaction time in women +58 ms, in men -31 ms, P = 0.05). In conclusion, cognitive-motor function is preserved during water deprivation in young humans up to a moderate dehydration level of 2.6% of body weight. Sexual dimorphism for reaction time-based performance is present. Increased subjective task-related effort suggests that healthy volunteers exhibit cognitive compensating mechanisms for increased tiredness and reduced alertness during slowly progressive moderate dehydration.     

Sensorimotor Modulation Differs with Load Type during Constant Finger Force or Position

During submaximal isometric contraction, there are two different load types: production of a constant force against a rigid restraint (force task), and maintenance of position against a constant load (position task). Previous studies reported that the time to task failure during a fatigue task was twice as long in the force task compared with the position task. Sensory feedback processing may contribute to these differences. The purpose of the current study was to determine the influence of load types during static muscle contraction tasks on the gating effect, i.e., attenuation of somatosensory-evoked potentials (SEPs) and the cortical silent period (cSP). Ten healthy subjects contracted their right first dorsal interosseus muscle by abducting their index finger for 90 s, to produce a constant force against a rigid restraint that was 20% of the maximum voluntary contraction (force task), or to maintain a constant position with 10° abduction of the metacarpophalangeal joint against the same load (position task). Somatosensory evoked potentials (SEPs) were recorded from C3′ by stimulating either the right ulnar or median nerve at the wrist while maintaining contraction. The cortical silent period (cSP) was also elicited by transcranial magnetic stimulation. Reduction of the amplitude of the P45 component of SEPs was significantly larger during the position task than during the force task and under control rest conditions when the ulnar nerve, but not the median nerve, was stimulated. The position task had a significantly shorter cSP duration than the force task. These results suggest the need for more proprioceptive information during the position task than the force task. The shorter duration of the cSP during the position task may be attributable to larger amplitude of heteronymous short latency reflexes. Sensorimotor modulations may differ with load type during constant finger force or position tasks.     

Alteration of nucleic acid structure and stability modulates the efficiency of minus-strand transfer mediated by the HIV-1 nucleocapsid protein

During human immunodeficiency virus type 1 minus-strand transfer, the nucleocapsid protein (NC) facilitates annealing of the complementary repeat regions at the 3'-ends of acceptor RNA and minus-strand strong-stop DNA ((-) SSDNA). In addition, NC destabilizes the highly structured complementary trans-activation response element (TAR) stem-loop (TAR DNA) at the 3'-end of (-) SSDNA and inhibits TAR-induced self-priming, a dead-end reaction that competes with minus-strand transfer. To investigate the relationship between nucleic acid secondary structure and NC function, a series of truncated (-) SSDNA and acceptor RNA constructs were used to assay minus-strand transfer and self-priming in vitro. The results were correlated with extensive enzymatic probing and mFold analysis. As the length of (-) SSDNA was decreased, self-priming increased and was highest when the DNA contained little more than TAR DNA, even if NC and acceptor were both present; in contrast, truncations within TAR DNA led to a striking reduction or elimination of self-priming. However, destabilization of TAR DNA was not sufficient for successful strand transfer: the stability of acceptor RNA was also crucial, and little or no strand transfer occurred if the RNA was highly stable. Significantly, NC may not be required for in vitro strand transfer if (-) SSDNA and acceptor RNA are small, relatively unstructured molecules with low thermodynamic stabilities. Collectively, these findings demonstrate that for efficient NC-mediated minus-strand transfer, a delicate thermodynamic balance between the RNA and DNA reactants must be maintained.     

Oligonucleotide inhibition of the interaction of HIV-1 Tat protein with the trans-activation responsive region (TAR) of HIV RNA

The interaction of HIV-1 Tat protein with its recognition sequence, the trans-activation responsive region TAR is a potential target for drug discovery against HIV infection. We show by use of an in vitro competition filter binding interference assay that synthetic oligodeoxyribonucleotides complementary to the HIV-1 TAR RNA apical stem-loop and bulge region inhibit the binding of Tat protein or a Tat peptide (residues 37-72) better than two small molecules that have been shown to bind TAR RNA, Hoechst 33258 and neomycin B. The inhibition is not sensitive to length between 13 and 16 residues or precise positioning but shorter oligonucleotides are less effective. Enhanced inhibition was obtained for a 16-mer 2'-O-methyl oligoribonucleotide but not for C5-propyne pyrimidine-substituted oligonucleotides. Control non-antisense oligonucleotides were occasionally also effective in filter binding interference but only the complementary antisense 2'-O-methyl oligoribonucleotide was effective in gel mobility shift assays in direct TAR binding or in interference with Tat peptide binding to the TAR stem-loop. This is the first demonstration of effective inhibition of the Tat-TAR interaction by nuclease-stabilized oligonucleotide analogues.     

Accessory muscle activity contributes to the variation in time to task failure for different arm postures and loads.

Time to failure and electromyogram activity were measured during two types of sustained submaximal contractions with the elbow flexors that required each subject to exert the same net muscle torque with the forearm in two different postures. Twenty men performed the tasks, either by maintaining a constant force while pushing against a force transducer (force task), or by supporting an equivalent load while maintaining a constant elbow angle (position task). The time to failure for the position task with the elbow flexed at 1.57 rad and the forearm horizontal was less than that for the force task (5.2 +/- 2.6 and 8.8 +/- 3.6 min, P = 0.003), whereas it was similar when the forearm was vertical (7.9 +/- 4.1 and 7.8 +/- 4.5 min, P = 0.995). The activity of the rotator cuff muscles was greater during the position tasks (25.1 +/- 10.1% maximal voluntary contraction) compared with the force tasks (15.2 +/- 5.4% maximal voluntary contraction, P < 0.001) in both forearm postures. However, the rates of increase in electromyogram of the accessory muscles and mean arterial pressure were greater for the position task only when the forearm was horizontal (P < 0.05), whereas it was similar for the elbow flexors. These findings indicate that forearm posture influences the difference in the time to failure for the two fatiguing contractions. When there was a difference between the two tasks, the task with the briefer time to failure involved greater rates of increase in accessory muscle activity and mean arterial pressure.     

A comparison of the contractile properties of the human gastrocnemius and soleus muscles

Twitch speeds and potentiating capacities have been determined for human medial and lateral gastrocnemius and soleus muscles. The experiments involved and application of submaximal stimuli to the respective muscle bellies, with monitoring of the evoked compound action potentials (M-waves) during repetitive stimulation. Contrary to an earlier report, the lateral gastrocnemius was found to have a significantly shorter mean contraction time (100.0 +/- 10.8 ms) than the soleus (156.5 +/- 14.7 ms) and this value was also significantly different from that of the medial gastrocnemius (113.7 +/- 19.6 ms). The mean half-relaxation time for each muscle also differed significantly from those for the other two muscles. A further contrast between the muscles was that potentiation of the twitch, following a 3-s tetanus at 50 Hz, was significantly greater in the lateral gastrocnemius than in soleus (mean values 60.4 +/- 43.1% and 2.6 +/- 3.3% respectively.     

The interhemispheric asymmetry of the spatial-temporal organization of cortical potentials in the rabbit]

In experiments on freely moving rabbits the existence of interhemispheric asymmetry of spatial-temporal organization of the cortical potentials in the state of calm alertness was shown. Episodes were revealed of interhemispheric discordance of spatial reconstructions of momentary reliefs of the cortical potentials topograms 1/64-1/3-1/5 s in duration, i.e. periods of the theta- or delta-rhythms. Total duration of time of interhemispheric asymmetry (according to significant divergences in dynamics of resemblance coefficients of consequent reliefs of the cortical potentials topograms) in most cases was not less than 10% and not more than 30% of time of analysis epoch and consisted of discordance episodes both of different global reconstructions of spatial correlations of the left and right hemisphere potentials and of interhemispheric local shifts in spatial organization of the cortex potentials.     

Study on the interactions between anti-HIV-1 active compounds with trans-activation response RNA by affinity capillary electrophoresis

The study on the interactions between two anti-human immunodeficiency virus type 1 (anti-HIV-1) active compounds with trans-activation response (TAR) RNA by affinity capillary electrophoresis (ACE) with UV absorbance detection is presented. The results showed that the novel active molecules could interact with TAR RNA and inhibit the reproduce process of HIV-1. The binding constants were estimated by the change of migration time of the analytes through the change of concentrations of TAR RNA in the buffer solution. The yielded binding constants of 8.87 x 10(3)M(-1) for active compound C(3) and 8.42 x 10(3)M(-1) for MC(3) at 20.0 degrees C, 0.626 x 10(3)M(-1) and 0.644 x 10(3)M(-1) at 37.0 degrees C, respectively. The thermodynamic parameters Delta H and DeltaS were obtained and shown that both hydrophobic and electrostatic interaction played roles in the binding processes. The results showed that the presented method was an easy and simple method to evaluate the interaction of small molecules with some bioactive materials.     

Pharmacokinetic analysis of polyamide nucleic-acid-cell penetrating peptide conjugates targeted against HIV-1 transactivation response element

We have demonstrated that polyamide nucleic acids complementary to the transactivation response (TAR) element of HIV-1 LTR inhibit HIV-1 production when transfected in HIV-1 infected cells. We have further shown that anti-TAR PNA (PNA(TAR)) conjugated with cell-penetrating peptide (CPP) is rapidly taken up by cells and exhibits strong antiviral and anti-HIV-1 virucidal activities. Here, we pharmacokinetically analyzed (125)I-labeled PNA(TAR) conjugated with two CPPs: a 16-mer penetratin derived from antennapedia and a 13-mer Tat peptide derived from HIV-1 Tat. We administered the (125)I-labeled PNA(TAR)-CPP conjugates to male Balb/C mice through intraperitoneal or gavage routes. The naked (125)I-labeled PNA(TAR) was used as a control. Following a single administration of the labeled compounds, their distribution and retention in various organs were monitored at various time points. Regardless of the administration route, a significant accumulation of each PNA(TAR)-CPP conjugate was found in different mouse organs and tissues. The clearance profile of the accumulated radioactivity from different organs displayed a biphasic exponential pathway whereby part of the radioactivity cleared rapidly, but a significant portion of it was slowly released over a prolonged period. The kinetics of clearance of individual PNA(TAR)-CPP conjugates slightly varied in different organs, while the overall biphasic clearance pattern remained unaltered regardless of the administration route. Surprisingly, unconjugated naked PNA(TAR) displayed a similar distribution and clearance profile in most organs studied although extent of its uptake was lower than the PNA(TAR)-CPP conjugates.     

Effects of monochromatic light on time sense for short intervals

We examined the effects of monochromatic light on the time sense and the central nervous system. Nine young adult volunteers participated in this study. They were exposed to red-light and blue-light environments (illuminance was kept at 310 lx). We evaluated the time sense by time-production tests of 90 s and 180 s and measured the P300 event-related potentials during an auditory oddball task. The 90-s time intervals produced by subjects in the two monochromatic light conditions were not significantly different. However, the 180-s time interval produced in the red-light condition (163.2+/-50.4 s) was significantly (p<0.05) shorter than that in the blue-light condition (199.0+/-54.4 s). The peak latency of P300 in the red light (322.2+/-26.6 ms) was found to be significantly (p<0.05) shorter also than that in the blue light (332.6+/-20.2 ms). The feelings measured by the visual analogue scales in the two light conditions were not significantly different. These results indicate that the time sense ran faster in the red-light than in the blue-light condition. We suggest that the higher activity in the central nervous system that is accounted for by the shorter latency of P300 is related to the acceleration of the time sense.     

A human chromosome 12-associated 83-kilodalton cellular protein specifically binds to the loop region of human immunodeficiency virus type 1 trans-activation response element RNA.

trans activation of human immunodeficiency virus type 1 (HIV-1) involves the viral trans-activator protein (Tat) and a cellular factor(s) encoded on human chromosome 12 (HuChr12) that targets the trans-activation response element (TAR) in the viral long terminal repeat. Because nascent TAR RNA is predicted to form a secondary structure that specifically binds cellular proteins, we investigated the composition of the TAR RNA-protein complex for HuChr12-specific proteins. UV cross-linking of TAR RNA-nuclear protein complexes formed in vitro identified an 83-kDa protein in human cells and in a human-hamster hybrid cell containing only HuChr12. The 83-kDa TAR RNA-binding protein was absent in the parental hamster cells. TAR RNA mutations that inhibited binding of the 83-kDa protein in vitro also inhibited HuChr12-dependent Tat trans activation. These TAR mutations changed the native sequence or secondary structure of the TAR loop. The TAR RNA binding activity of the 83-kDa protein also correlated with a HuChr12-dependent increase in steady-state HIV-1 RNA expression during Tat trans activation. Our results suggest that either a species-specific 83-kDa TAR RNA loop-binding protein is directly encoded on HuChr12 or a HuChr12 protein(s) induces the expression of an 83-kDa TAR-binding protein in nonprimate cells.     

Time to task failure and muscle activation vary with load type for a submaximal fatiguing contraction with the lower leg.

The purpose was to compare the time to failure and muscle activation patterns for a sustained isometric submaximal contraction with the dorsiflexor muscles when the foot was restrained to a force transducer (force task) compared with supporting an equivalent inertial load and unrestrained (position task). Fifteen men and women (mean+/-SD; 21.1+/-1.4 yr) performed the force and position tasks at 20% maximal voluntary contraction force until task failure. Maximal voluntary contraction force performed before the force and position tasks was similar (333+/-71 vs. 334+/-65 N), but the time to task failure was briefer for the position task (10.0+/-6.2 vs. 21.3+/-17.8 min, P<0.05). The rate of increase in agonist root-mean-square electromyogram (EMG), EMG bursting activity, rating of perceived exertion, fluctuations in motor output, mean arterial pressure, and heart rate during the fatiguing contraction was greater for the position task. EMG activity of the vastus lateralis (lower leg stabilizer) and medial gastrocnemius (antagonist) increased more rapidly during the position task, but coactivation ratios (agonist vs. antagonist) were similar during the two tasks. Thus the difference in time to failure for the two tasks with the dorsiflexor muscles involved a greater level of neural activity and rate of motor unit recruitment during the position task, but did not involve a difference in coactivation. These findings have implications for rehabilitation and ergonomics in minimizing fatigue during prolonged activation of the dorsiflexor muscles.     

Dominant role of the 5' TAR bulge in dimerization of HIV-1 genomic RNA, but no evidence of TAR-TAR kissing during in vivo virus assembly

The 5' untranslated region of HIV-1 genomic RNA (gRNA) contains two stem-loop structures that appear to be equally important for gRNA dimerization: the 57-nucleotide 5' TAR, at the very 5' end, and the 35-nucleotide SL1 (nucleotides 243-277). SL1 is well-known for containing the dimerization initiation site (DIS) in its apical loop. The DIS is a six-nucleotide palindrome. Here, we investigated the mechanism of TAR-directed gRNA dimerization. We found that the trinucleotide bulge (UCU24) of the 5' TAR has dominant impacts on both formation of HIV-1 RNA dimers and maturation of the formed dimers. The ΔUCU trinucleotide deletion strongly inhibited the first process and blocked the other, thus impairing gRNA dimerization as severely as deletion of the entire 5' TAR, and more severely than deletion of the DIS, inactivation of the viral protease, or most severe mutations in the nucleocapsid protein. The apical loop of TAR contains a 10-nucleotide palindrome that has been postulated to stimulate gRNA dimerization by a TAR-TAR kissing mechanism analogous to the one used by SL1 to stimulate dimerization. Using mutations that strongly destabilize formation of the TAR palindrome duplex, as well as compensatory mutations that restore duplex formation to a wild-type-like level, we found no evidence of TAR-TAR kissing, even though mutations nullifying the kissing potential of the TAR palindrome could impair dimerization by a mechanism other than hindering of SL1. However, nullifying the kissing potential of TAR had much less severe effects than ΔUCU. By not uncovering a dimerization mechanism intrinsic to TAR, our data suggest that TAR mutations exert their effect 3' of TAR, yet not on SL1, because TAR and SL1 mutations have synergistic effects on gRNA dimerization.     

Forearm blood flow follows work rate during submaximal dynamic forearm exercise independent of sex.

To test the hypothesis that sex influences forearm blood flow (FBF) during exercise, 15 women and 16 men of similar age [women 24.3 +/- 4.0 (SD) vs. men 24.9 +/- 4.5 yr] but different forearm muscle strength (women 290.7 +/- 44.4 vs. men 509.6 +/- 97.8 N; P < 0.05) performed dynamic handgrip exercise as the same absolute workload was increased in a ramp function (0.25 W/min). Task failure was defined as the inability to maintain contraction rate. Blood pressure and FBF were measured on separate arms during exercise by auscultation and Doppler ultrasound, respectively. Muscle strength was positively correlated with endurance time (r = 0.72, P < 0.01) such that women had a shorter time to task failure than men (450.5 +/- 113.0 vs. 831.3 +/- 272.9 s; P < 0.05). However, the percentage of maximal handgrip strength achieved at task failure was similar between sexes (14% maximum voluntary contraction). FBF was similar between women and men throughout exercise and at task failure (women 13.6 +/- 5.3 vs. men 14.5 +/- 4.9 ml.min(-1).100 ml(-1)). Mean arterial pressure was lower in women at rest and during exercise; thus calculated forearm vascular conductance (FVC) was higher in women during exercise but similar between sexes at task failure (women 0.13 +/- 0.05 vs. men 0.11 +/- 0.04 ml.min(-1).100 ml(-1).mmHg(-1)). In conclusion, the similar FBF during exercise was achieved by a higher FVC in the presence of a lower MAP in women than men. Still, FBF remained coupled to work rate (and presumably metabolic demand) during exercise irrespective of sex.