一阶运动和二阶运动方向辨别的知觉学习及传递性研究

为了明确视觉系统对一阶运动和二阶运动识别机制之间的相互关系,采用一阶运动和二阶运动的正弦光栅刺激,在旁中央凹对训练组(14名被试)进行运动方向辨别的知觉学习训练．通过比较训练前后的对比敏感度变化,并同对照组(11名被试)的结果比较后发现：a．在旁中央凹,一阶运动光栅方向辨别的训练提高了被试辨别一阶运动方向的能力,但是这种提高的效果却不能传递到二阶运动光栅的方向辨别任务当中;b．二阶运动光栅方向辨别的训练在提高被试二阶运动方向识别能力的同时,也提高了被试在一阶运动光栅方向辨别任务中的表现．这一训练效果的“非对称”传递现象提示,人的视觉系统中存在两种不同的机制分别用于感知一阶运动和二阶运动,但这两种机制并非截然不同,而是部分分离的．     

Binocular Combination of Second-Order Stimuli

Phase information is a fundamental aspect of visual stimuli. However, the nature of the binocular combination of stimuli defined by modulations in contrast, so-called second-order stimuli, is presently not clear. To address this issue, we measured binocular combination for first- (luminance modulated) and second-order (contrast modulated) stimuli using a binocular phase combination paradigm in seven normal adults. We found that the binocular perceived phase of second-order gratings depends on the interocular signal ratio as has been previously shown for their first order counterparts; the interocular signal ratios when the two eyes were balanced was close to 1 in both first- and second-order phase combinations. However, second-order combination is more linear than previously found for first-order combination. Furthermore, binocular combination of second-order stimuli was similar regardless of whether the carriers in the two eyes were correlated, anti-correlated, or uncorrelated. This suggests that, in normal adults, the binocular phase combination of second-order stimuli occurs after the monocular extracting of the second-order modulations. The sensory balance associated with this second-order combination can be obtained from binocular phase combination measurements.     

Thermal stability of dehydrophenylalanine-containing model peptides as probed by infrared spectroscopy: a case study of an alpha-helical and a 3(10)-helical peptide

The temperature-dependent secondary-structural changes in the two known helical model peptides Boc-Val-deltaPhe-Ala-Leu-Gly-OMe (1; alpha-helical) and Boc-Leu-Phe-Ala-deltaPhe-Leu-OMe (2; 3(10)-helical), which both comprise a single dehydrophenylalanine (deltaPhe) residue, were investigated by means of FT-IR spectroscopy (peptide film on KBr). Both the first-order and the better-resolved second-order derivative IR spectra of 1 and 2 were analyzed. The nu(NH) (3240-3340 cm(-1)), the Amide-I (1600-1700 cm(-1)), and the Amide-II (1510-1580 cm(-1)) regions of 1 and 2 showed significant differences in thermal-denaturation experiments (22 degrees --> 144 degrees), with the 3(10)-helical peptide (2) being considerably more stable. This observation was rationalized by different patterns and strengths of intramolecular H-bonds, and was qualitatively related to the different geometries of the peptides. Also, a fair degree of residual secondary-structural elements were found even in the 'denatured' states above 104 degrees (1) or 134 degrees (2).     

Fast kinetics of calcium dissociation from calsequestrin

We measured the kinetics of calcium dissociation from calsequestrin in solution or forming part of isolated junctional sarcoplasmic reticulum membranes by mixing calsequestrin equilibrated with calcium with calcium-free solutions in a stopped-flow system. In parallel, we measured the kinetics of the intrinsic fluorescence changes that take place following calcium dissociation from calsequestrin. We found that at 25 degrees C calcium dissociation was 10-fold faster for calsequestrin attached to junctional membranes (k = 109 s(-1)) than in solution. These results imply that calcium dissociation from calsequestrin in vivo is not rate limiting during excitation-contraction coupling. In addition, we found that the intrinsic fluorescence decrease for calsequestrin in solution or forming part of junctional membranes was significantly slower than the rates of calcium dissociation. The kinetics of intrinsic fluorescence changes had two components for calsequestrin associated to junctional membranes and only one for calsequestrin in solution; the faster component was 8-fold faster (k = 54.1 s(-1)) than the slower component (k = 6.9 s(-1)), which had the same k value as for calsequestrin in solution. These combined results suggest that the presence of calsequestrin at high concentrations in a restricted space, such as when bound to the junctional membrane, accelerates calcium dissociation and the resulting structural changes, presumably as a result of cooperative molecular interactions.     

Active knee joint velocity replication measures are stable and accurate in healthy individuals

The purpose of this study was to determine the stability and accuracy of active knee joint velocity replication methods in healthy subjects. We used a repeated measures design with 14 healthy volunteers. Measures of velocity replication were performed in two ranges of knee joint flexion (0 degrees -30 degrees and 60 degrees -90 degrees ), across four testing velocities (5, 10, 15, and 30 degrees /s) in two movement directions (flexion and extension). Statistical analysis included intraclass correlation coefficients (ICCs; 2, k) and associated standard error of the measures calculated between day 1 and 2. We performed z-tests between all possible combinations of ICC pairs using Fisher's Z transformations to determine if any significant differences existed between observed ICCs. We also calculated correlation ratios (eta2) to explain the source of variability in the calculated ICCs. To assess measurement accuracy, we calculated constant error and absolute error between criterion and replication velocities. Results on ICCs and standard error of the measurements (SEMs) ranged from r = -0.44 +/- 7.00 to 0.88 +/- 0.72 degrees /s. Calculated z-tests indicated six paired ICCs were significantly different ( p < 0.1). In all six pairs, the faster test velocity had a lower ICC magnitude. The eta2 calculations demonstrated that inconsistent performance between day 1 and 2 caused the low ICC magnitudes observed with faster testing velocities. Significantly more absolute error occurred at 30 and 15 degrees /s compared with 5 degrees /s. Significantly less constant error was observed for 30 degrees /s compared with 15 degrees /s. A significant direction by range of motion interaction indicated less constant error for flexion movements in the 60 degrees -90 degrees range of motion (ROM) as compared with extension movements in either ROM. Healthy individuals could actively replicate slower criterion velocities in the mid and end ranges of knee joint motion in both movement directions with an acceptable amount of consistency and accuracy. The data support the use of velocity replication in future investigations on proprioceptive function.     

Ontogenetic improvement of visual function in the medaka Oryzias latipes based on an optomotor testing system for larval and adult fish

We developed a system for evaluation of visual function in larval and adult fish. Both optomotor (swimming) and optokinetic (eye movement) responses were monitored and recorded using a system of rotating stripes. The system allowed manipulation of factors such as width of the stripes used, rotation speed of the striped drum, and light illuminance levels within both the scotopic and photopic ranges. Precise control of these factors allowed quantitative measurements of visual acuity and motion detection. Using this apparatus, we tested the hypothesis that significant posthatch ontogenetic improvements in visual function occur in the medaka Oryzias latipes, and also that this species shows significant in ovo neuronal development. Significant improvements in the acuity angle alpha (ability to discriminate detail) were observed from approximately 5 degrees at hatch to 1 degree in the oldest adult stages. In addition, we measured a significant improvement in flicker fusion thresholds (motion detection skills) between larval and adult life stages within both the scotopic and photopic ranges of light illuminance. Ranges of flicker fusion thresholds (X±SD) at log I=1.96 (photopic) varied from 37.2±1.6 cycles/s in young adults to 18.6±1.6 cycles/s in young larvae 10 days posthatch. At log I=−2.54 (scotopic), flicker fusion thresholds varied from 5.8±0.7 cycles/s in young adults to 1.7±0.4 cycles/s in young larvae 10 days posthatch. Light sensitivity increased approximately 2.9 log units from early hatched larval stages to adults. The demonstrated ontogenetic improvements in visual function probably enable the fish to explore new resources, thereby enlarging their fundamental niche.Copyright 2002 The Association for the Study of Animal Behaviour. Published by Elsevier Science Ltd. All rights reserved .     

Direct evidence for encoding of motion streaks in human visual cortex

Temporal integration in the visual system causes fast-moving objects to generate static, oriented traces (‘motion streaks’), which could be used to help judge direction of motion. While human psychophysics and single-unit studies in non-human primates are consistent with this hypothesis, direct neural evidence from the human cortex is still lacking. First, we provide psychophysical evidence that faster and slower motions are processed by distinct neural mechanisms: faster motion raised human perceptual thresholds for static orientations parallel to the direction of motion, whereas slower motion raised thresholds for orthogonal orientations. We then used functional magnetic resonance imaging to measure brain activity while human observers viewed either fast (‘streaky’) or slow random dot stimuli moving in different directions, or corresponding static-oriented stimuli. We found that local spatial patterns of brain activity in early retinotopic visual cortex reliably distinguished between static orientations. Critically, a multivariate pattern classifier trained on brain activity evoked by these static stimuli could then successfully distinguish the direction of fast (‘streaky’) but not slow motion. Thus, signals encoding static-oriented streak information are present in human early visual cortex when viewing fast motion. These experiments show that motion streaks are present in the human visual system for faster motion.     

Electromyographic instantaneous amplitude and instantaneous mean power frequency patterns across a range of motion during a concentric isokinetic muscle action of the biceps brachii.

The purpose of this study was to examine the electromyographic (EMG) instantaneous amplitude (IA) and instantaneous mean power frequency (IMPF) patterns for the biceps brachii muscle across a range of motion during maximal and submaximal concentric isokinetic muscle actions of the forearm flexors. Ten adults (mean +/- SD age = 22.0 +/- 3.4 years) performed a maximal and a submaximal [20% peak torque (PT)] concentric isokinetic forearm flexion muscle action at a velocity of 30 degrees s(-1). The surface EMG signal was detected from the biceps brachii muscle with a bipolar electrode arrangement, and the EMG IA and IMPF versus time relationships were examined for each subject using first- and second-order polynomial regression models. The results indicated that there were no consistent patterns between subjects for EMG IA or IMPF with increases in torque across the range of motion. Some of the potential nonphysiological factors that could influence the amplitude and/or frequency contents of the surface EMG signal during a dynamic muscle action include movement of the muscle fibers and innervation zone beneath the skin surface, as well as changes in muscle fiber length and the thickness of the tissue layer between the muscle and the recording electrodes. These factors may affect the EMG IA and IMPF patterns differently for each subject, thereby increasing the difficulty of drawing any general conclusions regarding the motor control strategies that increase torque across a range of motion.     

Kinetics and equilibria in ligand binding by nitrophorins 1-4: evidence for stabilization of a nitric oxide-ferriheme complex through a ligand-induced conformational trap

Nitrophorins 1-4 (NP1-4) are ferriheme proteins from the blood-sucking insect Rhodnius prolixus that transport nitric oxide (NO) to the victim, sequester histamine, and inhibit blood coagulation. Here, we report kinetic and thermodynamic analyses for ligand binding by all four proteins and their reduction potentials. All four undergo biphasic association and dissociation reactions with NO. The initial association is fast (1.5-33 microM(-)(1) s(-)(1)) and similar to that of elephant metmyoglobin. However, unlike in metmyoglobin, a slower second phase follows ( approximately 50 s(-)(1)), and the stabilized final complexes are resistant to autoreduction (E degrees = +3 to +154 mV vs normal hydrogen electrode). NO dissociation begins with a slow, pH-dependent step (0.02-1.4 s(-)(1)), followed by a faster phase that is again similar to that of metmyoglobin (3-52 s(-)(1)). The equilibrium dissociation constants are quite small (1-850 nM). NP1 and NP4 display larger release rate constants and smaller association rate constants than NP2 and NP3, leading to values for K(d) that are about 10-fold greater. The results are discussed in light of the recent crystal structures of NP1, NP2, and NP4, which display open, polar distal pockets, and of NP4-NO, which displays an NO-induced conformational change that leads to expulsion of solvent and complete burial of the NO ligand in a now nonpolar distal pocket. Taken together, the results suggest that tighter NO binding in the nitrophorins is due to the trapping of the molecule in a nonpolar distal pocket rather than through formation of particularly strong Fe-NO or hydrogen bonds.     

Baboons (Papio papio) spontaneously process the first-order but not second-order configural properties of faces

A two-alternative forced-choice discrimination task was used to assess whether baboons (N=7) spontaneously process qualitative (i.e., first-order) or quantitative (i.e., second-order) variations in the configural arrangement of facial features. Experiment 1 used as test stimuli second-order pictorial faces of humans or baboons in which the mouth and the eyes were rotated upside down relative to the normal face. Baboons readily discriminated two different normal faces but did not discriminate a normal face from its second-order modified version. Experiment 2 used human or baboon faces for which the first-order configural properties had been distorted by reversing the location of the eyes and mouth within the face. Discrimination was prompt with these stimuli. Experiment 3 replicated some of the conditions and the results of experiment 1, thus ruling out possible effects of learning. It is concluded that baboons are more adept at spontaneously processing first- than second-order configural facial properties, similar to what is known in the human developmental literature.     

Cerebrovascular responsiveness to steady-state changes in end-tidal CO2 during passive heat stress.

This study tested the hypothesis that passive heat stress alters cerebrovascular responsiveness to steady-state changes in end-tidal CO(2) (Pet(CO(2))). Nine healthy subjects (4 men and 5 women), each dressed in a water-perfused suit, underwent normoxic hypocapnic hyperventilation (decrease Pet(CO(2)) approximately 20 Torr) and normoxic hypercapnic (increase in Pet(CO(2)) approximately 9 Torr) challenges under normothermic and passive heat stress conditions. The slope of the relationship between calculated cerebrovascular conductance (CBVC; middle cerebral artery blood velocity/mean arterial blood pressure) and Pet(CO(2)) was used to evaluate cerebrovascular CO(2) responsiveness. Passive heat stress increased core temperature (1.1 +/- 0.2 degrees C, P < 0.001) and reduced middle cerebral artery blood velocity by 8 +/- 8 cm/s (P = 0.01), reduced CBVC by 0.09 +/- 0.09 CBVC units (P = 0.02), and decreased Pet(CO(2)) by 3 +/- 4 Torr (P = 0.07), while mean arterial blood pressure was well maintained (P = 0.36). The slope of the CBVC-Pet(CO(2)) relationship to the hypocapnic challenge was not different between normothermia and heat stress conditions (0.009 +/- 0.006 vs. 0.009 +/- 0.004 CBVC units/Torr, P = 0.63). Similarly, in response to the hypercapnic challenge, the slope of the CBVC-Pet(CO(2)) relationship was not different between normothermia and heat stress conditions (0.028 +/- 0.020 vs. 0.023 +/- 0.008 CBVC units/Torr, P = 0.31). These results indicate that cerebrovascular CO(2) responsiveness, to the prescribed steady-state changes in Pet(CO(2)), is unchanged during passive heat stress.     

Effects of walking speed, strength and range of motion on gait stability in healthy older adults

Falls pose a tremendous risk to those over 65 and most falls occur during locomotion. Older adults commonly walk slower, which many believe helps improve walking stability. While increased gait variability predicts future fall risk, increased variability is also caused by walking slower. Thus, we need to better understand how differences in age and walking speed independently affect dynamic stability during walking. We investigated if older adults improved their dynamic stability by walking slower, and how leg strength and flexibility (passive range of motion (ROM)) affected this relationship. Eighteen active healthy older and 17 healthy younger adults walked on a treadmill for 5min each at each of 5 speeds (80-120% of preferred). Local divergence exponents and maximum Floquet multipliers (FM) were calculated to quantify each subject's inherent local dynamic stability. The older subjects walked with the same preferred walking speeds as the younger subjects (p=0.860). However, these older adults still exhibited greater local divergence exponents (p<0.0001) and higher maximum FM (p<0.007) than the younger adults at all walking speeds. These older adults remained more locally unstable (p<0.04) even after adjusting for declines in both strength and ROM. In both age groups, local divergence exponents decreased at slower speeds and increased at faster speeds (p<0.0001). Maximum FM showed similar changes with speed (p<0.02). Both younger and older adults exhibited decreased instability by walking slower, in spite of increased variability. These increases in dynamic instability might be more sensitive indicators of future fall risk than changes in gait variability.     

Motion: the long and short of it

Several authors have proposed that motion is analyzed by two separate processes: short-range and long-range. We claim that the differences between short-range and long-range motion phenomena are a direct consequence of the stimuli used in the two paradigms and are not evidence for the existence of two qualitatively different motion processes. We propose that a single style of motion analysis, similar to the well known Reichardt and Marr-Ullman motion detectors, underlies all motion phenomena. Although there are different detectors of this type specialized for different visual attributes (namely first-order and second-order stimuli), they all share the same mode of operation. We review the studies of second-order motion stimuli to show that they share the basic phenomena observed for first-order stimuli. The similarity across stimulus types suggests, not parallel streams of motion extraction, one short-range and passive and the other long-range and intelligent, but a concatenation of a common mode of initial motion extraction followed by a general inference process.     

Comments on Cavanagh and Mather (1989): coming up short (and long)

Cavanagh and Mather (1989) reviewed literature concerning the possible distinction between short- and long-range processes in motion perception and concluded that the distinction cannot be supported. Instead, they proposed that motion perception be considered on the basis of detectors for first-order (luminance, color) and second-order (first-order motion, texture, stereo) stimulus attributes. They supported their position with studies of motion based on second-order stimuli. The present paper contends that when experiments permitting the investigation of both processes in the same display are included and when criteria are examined in their totality rather than one-by-one, the original short-range/long-range distinction can be retained. Furthermore, it is argued that the first-order/second-order distinction does not represent a theoretical advancement and that studies of second-order motion can be interpreted in terms of the older distinction. It is concluded that the short-range/long-range distinction is useful and should not be abandoned.     

Response time is more important than walking speed for the ability of older adults to avoid a fall after a trip.

We previously reported that the probability of an older adult recovering from a forward trip and using a "lowering" strategy increases with decreased walking velocity and faster response time. To determine the within-subject interaction of these variables we asked three questions: (1) Is the body orientation at the time that the recovery foot is lowered to the ground ("tilt angle") critical for successful recovery? (2) Can a simple inverted pendulum model, using subject-specific walking velocity and response time as input variables, predict this body orientation, and thus success of recovery? (3) Is slower walking velocity or faster response time more effective in preventing a fall after a trip? Tilt angle was a perfect predictor of a successful recovery step, indicating that the recovery foot placement must occur before the tilt angle exceeds a critical value of between 23 degrees and 26 degrees from vertical. The inverted pendulum model predicted the tilt angle from walking velocity and response time with an error of 0.4+/-2.2 degrees and a correlation coefficient of 0.93. The model predicted that faster response time was more important than slower walking velocity for successful recovery. In a typical individual who is at risk for falling, we predicted that a reduction of response time to a normal value allows a 77% increase in safe walking velocity. The mathematical model produced patient-specific recommendations for fall prevention, and suggested the importance of directing therapeutic interventions toward improving the response time of older adults.     

Muscle protein metabolism responds similarly to exogenous amino acids in healthy younger and older adults during NO-induced hyperemia

The combination of increasing blood flow and amino acid (AA) availability provides an anabolic stimulus to the skeletal muscle of healthy young adults by optimizing both AA delivery and utilization. However, aging is associated with a blunted response to anabolic stimuli and may involve impairments in endothelial function. We investigated whether age-related differences exist in the muscle protein anabolic response to AAs between younger (30 ± 2 yr) and older (67 ± 2 yr) adults when macrovascular and microvascular leg blood flow were similarly increased with the nitric oxide (NO) donor, sodium nitroprusside (SNP). Regardless of age, SNP+AA induced similar increases above baseline (P ≤ 0.05) in macrovascular flow (4.3 vs. 4.4 ml·min(-1)·100 ml leg(-1) measured using indocyanine green dye dilution), microvascular flow (1.4 vs. 0.8 video intensity/s measured using contrast-enhanced ultrasound), phenylalanine net balance (59 vs. 68 nmol·min(-1)·100 ml·leg(-1)), fractional synthetic rate (0.02 vs. 0.02%/h), and model-derived muscle protein synthesis (62 vs. 49 nmol·min(-1)·100 ml·leg(-1)) in both younger vs. older individuals, respectively. Provision of AAs during NO-induced local skeletal muscle hyperemia stimulates skeletal muscle protein metabolism in older adults to a similar extent as in younger adults. Our results suggest that the aging vasculature is responsive to exogenous NO and that there is no age-related difference per se in AA-induced anabolism under such hyperemic conditions.     

Electron transfer from the Rieske iron-sulfur protein (ISP) to cytochrome f in vitro. Is a guided trajectory of the ISP necessary for competent docking?

The time course of electron transfer in vitro between soluble domains of the Rieske iron-sulfur protein (ISP) and cytochrome f subunits of the cytochrome b(6)f complex of oxygenic photosynthesis was measured by stopped-flow mixing. The domains were derived from Chlamydomonas reinhardtii and expressed in Escherichia coli. The expressed 142-residue soluble ISP apoprotein was reconstituted with the [2Fe-2S] cluster. The second-order rate constant, k(2)((ISP-f)) = 1.5 x 10(6) m(-1) s(-1), for ISP to cytochrome f electron transfer was <10(-2) of the rate constant at low ionic strength, k(2)((f-PC))(> 200 x 10(6) m(-1) s(-1)), for the reduction of plastocyanin by cytochrome f, and approximately 1/30 of k(2)((f-PC)) at the ionic strength estimated for the thylakoid interior. In contrast to k(2)((f-PC)), k(2)((ISP-f)) was independent of pH and ionic strength, implying no significant role of electrostatic interactions. Effective pK values of 6.2 and 8.3, respectively, of oxidized and reduced ISP were derived from the pH dependence of the amplitude of cytochrome f reduction. The first-order rate constant, k(1)((ISP-f)), predicted from k(2)((ISP-f)) is approximately 10 and approximately 150 times smaller than the millisecond and microsecond phases of cytochrome f reduction observed in vivo. It is proposed that in the absence of electrostatic guidance, a productive docking geometry for fast electron transfer is imposed by the guided trajectory of the ISP extrinsic domain. The requirement of a specific electrically neutral docking configuration for ISP electron transfer is consistent with structure data for the related cytochrome bc(1) complex.     

Growth of Listeria monocytogenes and Yersinia enterocolitica colonies under modified atmospheres at 4 and 8 degrees C using a model food system

The growth of Listeria monocytogenes and Yersinia enterocolitica colonies was studied on solid media at 4 and 8 degrees C under modified atmospheres (MAs) of 5% O2: 10% CO2: 85% N2 (MA1), 30% CO2: 70% N2 (MA2) and air (control). Colony radius, determined using computer image analysis, allowed specific growth rates (mu) and the time taken to detect bacterial colonies to be estimated, after colonies became visible. At 4 degrees C both MAs decreased the growth rates of L. monocytogenes by 1.5- and 3.0-fold under MA1 (mu = 0.02 h(-1)) and MA2 (mu = 0.01 h(-1)), respectively, as compared with the control (mu = 0.03 h(-1)). The time to detection of bacterial colonies was increased from 15 d (control) to 24 (MA1) and 29 d (MA2). At 8 degrees C MA2 decreased the growth rate by 1.5-fold (mu = 0.04 h(-1)) as compared with the control (mu = 0.06 h(-1)) and detection of colonies increased from 7 (control) to 9 d (MA2). At 4 degrees C both MAs decreased the growth rates of Y. enterocolitica by 1.5- and 2.5-fold under MA1 (mu = 0.03 h(-1)) and MA2 (mu = 0.02 h(-1)), respectively, as compared with the control (mu = 0.05 h(-1)). At 8 degrees C identical growth rates were obtained under MA1 and the control (mu = 0.07 h(-1)) whilst a decrease in the growth rate was obtained under MA2 (mu = 0.04 h(-1)). The detection of colonies varied from 6 (8 degrees C, aerobic) to 19 d (4 degrees C, MA2). Refrigerated modified atmosphere packaged foods should be maintained at 4 degrees C and below to ensure product safety.     

Quantification and characterization of P-glycoprotein-substrate interactions

It is generally accepted that P-glycoprotein binds its substrates in the lipid phase of the membrane. Quantification and characterization of the lipid-transporter binding step are, however, still a matter of debate. We therefore selected 15 structurally diverse drugs and measured the binding constants from water to the activating (inhibitory) binding region of P-glycoprotein, K(tw(1)) (K(tw(2))), as well as the lipid-water partition coefficients, K(lw). The former were obtained by measuring the concentrations of half-maximum activation (inhibition), K(1) (K(2)), in living NIH-MDR-G185 mouse embryo fibroblasts using a Cytosensor microphysiometer, and the latter were derived from surface activity measurements. This allowed determination of the membrane concentration of drugs at half-maximum P-glycoprotein activation (C(b(1)) = (0.02 to 67) mmol/L lipid), which is much higher than the corresponding aqueous concentration (K(1) = (0.02 to 376) microM). Moreover we determined the free energy of drug binding from water to the activating binding region of the transporter (DeltaG degrees (tw(1)) = (-30 to -54) kJ/mol), the free energy of drug partitioning into the lipid membrane (DeltaG degrees (lw) = (-23 to -34) kJ/mol), and, as the difference of the two, the free energy of drug binding from the lipid membrane to the activating binding region of the transporter (DeltaG degrees (tl(1)) = (-7 to -27) kJ/mol). For the compounds tested DeltaG degrees (tl(1)) was less negative than DeltaG degrees (lw) but varied more strongly. The free energies of substrate binding to the transporter within the lipid phase, DeltaG degrees (tl(1)), are consistent with a modular binding concept, where the energetically most efficient binding module comprises two hydrogen bond acceptor groups.     

Effect of age on O(2) uptake kinetics and the adaptation of muscle deoxygenation at the onset of moderate-intensity cycling exercise.

Phase 2 pulmonary O(2) uptake (Vo(2(p))) kinetics are slowed with aging. To examine the effect of aging on the adaptation of Vo(2(p)) and deoxygenation of the vastus lateralis muscle at the onset of moderate-intensity constant-load cycling exercise, young (Y) (n = 6; 25 +/- 3 yr) and older (O) (n = 6; 68 +/- 3 yr) adults performed repeated transitions from 20 W to work rates corresponding to moderate-intensity (80% estimated lactate threshold) exercise. Breath-by-breath Vo(2(p)) was measured by mass spectrometer and volume turbine. Deoxy (HHb)-, oxy-, and total Hb and/or myoglobin were determined by near-infrared spectroscopy (Hamamatsu NIRO-300). Vo(2(p)) data were filtered, interpolated to 1 s, and averaged to 5-s bins. HHb data were filtered and averaged to 5-s bins. Vo(2(p)) data were fit with a monoexponential model for phase 2, and HHb data were analyzed to determine the time delay from exercise onset to the start of an increase in HHb and thereafter were fit with a single-component exponential model. The phase 2 time constant for Vo(2(p)) was slower (P < 0.01) in O (Y: 26 +/- 7 s; O: 42 +/- 9 s), whereas the delay before an increase in HHb (Y: 12 +/- 2 s; O: 11 +/- 1 s) and the time constant for HHb after the time delay (Y: 13 +/- 10 s; O: 9 +/- 3 s) were similar in Y and O. However, the increase in HHb for a given increase in Vo(2(p)) (Y: 7 +/- 2 microM x l(-1) x min(-1); O: 13 +/- 4 microM x l(-1) x min(-1)) was greater (P < 0.01) in O compared with Y. The slower Vo(2(p)) kinetics in O compared with Y adults was accompanied by a slower increase of local muscle blood flow and O(2) delivery discerned from a faster and greater muscle deoxygenation relative to Vo(2(p)) in O.