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Biomedical subjects

R L Marsh

Publications and source records attributed to R L Marsh.

52 records · Page 3Linked to original sources

Reduction in microtubule dynamics in vitro by brain microtubule-associated proteins and by a microtubule-associated protein-2 second repeated sequence analogue.

Microtubule-associated protein (MAP) binding to assembled microtubules (MTs) can be reduced by the addition of polyglutamate without significant MT depolymerization or interference with MT elongation reactions. Ensuing polymer length redistribution in MAP-depleted MTs occurs on a time scale characteristic of that observed with MAP-free MTs. The redistribution phase occurs even in the absence of mechanical shearing and without appreciable effects from end-to-end annealing, as indicated by the time course of incremental changes in polymer length and MT number concentration. We also observed higher rates of MT length redistribution when the [MAP]/[tubulin] ratio was decreased. Together, these results demonstrate that MT length redistribution rates are greatly influenced by MAP content, and the data are compatible with the dynamic instability model. We also found that a peptide analogue corresponding to the second repeated sequence in the MT-binding region of MAP-2 can also markedly retard MT length redistribution kinetics, a finding that accords with the ability of this peptide to promote tubulin polymerization in the absence of MAPs and to displace MAP-2 from MTs. These results provide further evidence that MAPs can modulate MT assembly/disassembly dynamics and that peptide analogues can mimic the action of intact MAPs without the need for three contiguous repeated sequences in the MT-binding region.

Amino Acid Sequence↗

Contractile properties of the striated adductor muscle in the bay scallop Argopecten irradians at several temperatures.

The isometric and isotonic contractile properties of the cross-striated adductor muscle of the bay scallop (Argopecten irradians) were measured in vitro at 10, 15 and 20 degrees C. The length at which twitch force was maximal as a function of the closed length in situ (L0/Lcl) averaged 1.38 +/- 0.01 (mean +/- S.E.M.) at 10 degrees C. This length is very close to the typical length at maximum gape during natural swimming at this temperature. Passive force was very low over the range of lengths measured here; at L0, passive force averaged approximately 0.08 N cm-2, or only 0.5% of the corresponding peak twitch force. The mean peak isometric twitch force (Ptw,max) at 10 degrees C was 21.43 +/- 0.68 N cm-2 (S.E.M.), and the ratio of peak twitch force to tetanic force (Ptw,max/P0) averaged 0.89 +/- 0.01. Temperature did not affect either twitch force (Ptw), once fatigue was taken into account, or Ptw,max/P0. In contrast, the time-related properties of twitch contractions (latent period, tL; time to peak tension, tPtw; and time from peak tension to half-relaxation, t50%R) were positively modified by temperature at all temperatures measured (Q10 > 1.8). All three properties were more temperature-sensitive over the range 10-15 degrees C than over the range 15-20 degrees C. The force-velocity relationships of the striated adductor muscle were fitted to the hyperbolic-linear (HYP-LIN) equation. The force-velocity curves of the striated adductor muscle of the scallop were strongly influenced by temperature. Maximal velocity at zero force (Vmax), and therefore maximal power output, increased significantly with temperature. The Q10 over the temperature range 10-15 degrees C (1.42) was significantly lower than that over the range 15-20 degrees C (2.41). The shape of the force-velocity relationship, assessed through comparisons of the power ratio (Wmax/VmaxP0), was not influenced by temperature.

Animals↗

Mechanical performance of scallop adductor muscle during swimming.

Mechanical performance of skeletal muscle has long been the subject of intense interest, but the details of in vivo performance of individual skeletal muscles during normal locomotion remain largely unknown. Performance in vitro has been described with considerable precision under simplified loading conditions. The force production and shortening velocity of most muscles, however, probably change continuously during natural movements. Therefore, modelling in vivo performance on the basis of in vitro contractile properties is subject to large degrees of uncertainty. Designing in vitro experiments that effectively examine the limits of mechanical performance requires increasing knowledge of precisely how muscles are used during normal movements. We report here measurements of the mechanical performance of the adductor muscle in scallops during jet-propulsion swimming. Swimming in scallops is powered solely by the striated portion of the single adductor muscle. Exploiting this simple locomotor morphology with simultaneous high-resolution measurements of pressure and flow rate, we have recorded nearly instantaneous measurements of the performance of a single skeletal muscle during normal locomotion.

Animals↗

Regulation of glycolysis in the pectoralis muscles of seasonally acclimatized American goldfinches exposed to cold.

Regulation of glycolysis was assessed in winter- and summer-acclimatized goldfinches (Carduelis tristis). We exposed birds to a thermo-neutral temperature (30 degrees C), moderate cold (-15 degrees C), and severe cold (0 degrees C in an atmosphere of 21% O2-79% He), and then measured concentrations of glycogen, glycolytic intermediates, and citrate in the pectoralis muscles. Winter birds used less glycogen when exposed to moderate cold than did summer birds, confirming the carbohydrate sparing noted by Marsh and Dawson [Am. J. Physiol. 242 (Regulatory Integrative Comp. Physiol. 11): R563-R569, 1982]. However, depletion of muscle glycogen did not correlate with thermoregulatory failure in this study. Concentrations of glucose 6-phosphate and fructose 6-phosphate in the pectoralis muscles were approximately 1.9 and 0.3 mumol/g wet mass in birds exposed to thermoneutral temperatures. The levels of these intermediates fell 50-70% under conditions known to enhance flux through glycolysis as indicated by increased glucose turnover and glycogen depletion. This information identifies phosphofructokinase (PFK) as a major regulated step in glycolysis in these highly aerobic skeletal muscles. Winter birds maintained the inhibition of this step under conditions of moderate cold. However, concentrations of citrate, which have been hypothesized to be an important inhibitor of PFK, did not correlate with the observed pattern of inhibition. Therefore, if the enhanced beta-oxidative capacity of winter birds is important in the regulation of glycolysis, a mechanism other than the accumulation of citrate may be involved.

Acclimatization↗

Deactivation rate and shortening velocity as determinants of contractile frequency.

The kinetic properties of muscle that could influence locomotor frequency include rate of activation, rate of cross-bridge "attachment", intrinsic shortening velocity, and rate of deactivation. The latter two mechanisms are examined using examples from high-speed running in lizards and escape swimming in scallops. During running, inertial loading and elastic energy storage probably mitigate the effects of thermal alterations in intrinsic muscle shortening velocity. The result is a rather low thermal dependence of stride frequency over a 15-20 degree C temperature range. However, at lower temperatures, the longer times required for deactivation cause the thermal dependence of frequency to increase greatly. Scallops use a single muscle to swim by jet propulsion. In vivo shortening velocity in these animals also shows a low thermal dependence. As with high-speed running, the mechanics of jet propulsion may limit the effects of thermally induced changes in intrinsic shortening velocity. The largest thermal effect during swimming is on the initial phase of valve opening. The effects of temperature on the rate of deactivation of the adductor muscle could play an important role in limiting reextension of the muscle, which is dependent on elastic energy storage in the hinge ligament. These examples illustrate that the relative importance of various intrinsic contractile properties in controlling locomotor performance depends on the mechanics of the movements.

Animals↗

Secondary memory and very rapid forgetting.

Studies of recall in the absence of expectancy (e.g., Muter, 1980) have suggested that forgetting from primary memory is much more rapid than previously assumed. Two experiments examined the role of secondary memory, as reflected by encoding strategies, in determining this rate of forgetting. Experiment 1 demonstrated that the type of encoding specified by orienting tasks can influence recall in a traditional Brown-Peterson task. Experiment 2 demonstrated a similar pattern of effects of orienting task in the Muter task when recall was not expected, despite much more rapid forgetting. The type of encoding engaged by the orienting tasks did not account for Muter's results. Expectancy and orienting task appear to have separable influences on resource allocation during encoding. The presence of secondary memory influences at even the shortest retention interval indicates that forgetting from primary memory may be even more rapid than has been proposed.

Adolescent↗

Ontogenesis of contractile properties of skeletal muscle and sprint performance in the lizard Dipsosaurus dorsalis.

Ontogenetic allometries of running performance in 3- to 4-m burst runs (sprints) and of the contractile properties of the fast-twitch, glycolytic region of the iliofibularis muscle (FG-IF) were measured in Dipsosaurus dorsalis. This iguanid lizard hatches at a body mass of about 4 g and reaches adult masses of 40-70 g. Running velocity was little influenced by changes in body mass during development. Stride frequency (f) declines ontogenetically and was proportional to body mass (Mb) to approximately the -0.2 power (determined by regression analysis). Stride length (Ls) appeared to be related to the allometry of hindlimb length (LHL); both Ls and LHL were proportional to about Mb0.28. Intrinsic shortening velocity of the FG-IF decreased only slightly with increasing body mass, and was consequently not proportional to f as has been assumed by various models of running dynamics. In contrast, twitch time lengthened markedly with increasing body mass, and the ratio of twitch time to stride time remained approximately constant. These results suggest that the intrinsic velocity of the muscles does not directly or solely determine maximal f, but instead limb kinematics are determined in part by other biomechanical constraints related to body dimensions. Further, the allometry of twitch kinetics supports the idea that the properties of the muscles are adjusted to allow ample time for full activation and deactivation within the biomechanically determined stride time.

Aging↗

Properties enhancing aerobic capacity of calling muscles in gray tree frogs Hyla versicolor.

The muscle features that accommodate the extraordinarily high aerobic respiration during calling by the gray tree frog Hyla versicolor were examined. We compared the muscles used for calling by males (external and internal obliques and laryngeal muscles) with the homologous muscles of females and with the leg muscles of males and females. The leg muscles consisted of 75% by volume fast glycolytic fibers, a composition typical of other muscles described in anuran amphibians. In contrast the calling muscles of males consisted of 100% fast oxidative fibers and had citrate synthase (CS) activities among the highest recorded for ectothermic vertebrates, 65-80 mumol X min-1 X g fresh mass-1. We also noted a strong sexual dimorphism in size and oxidative capacity of these muscles. The external and internal obliques of females weighed an order of magnitude less than the corresponding muscles of males and had CS activities of only 6 mumol X min-1 X g-1. Morphometric measurements of transmission electron micrographs revealed that the calling muscles of males contained high mitochondrial densities (approximately 20% of fiber volume) and capillary densities (approximately 700 mm-2) compared with a representative hindlimb muscle, the sartorius (mitochondrial density, 6% of fiber volume; capillary density, 230 mm-2). These frog muscles, which operate at approximately 20 degrees C, have lower capillary densities per mitochondrial volume than are found in mammalian muscles that function at higher temperatures.

3-Hydroxyacyl CoA Dehydrogenases↗

Thermal dependence of contractile properties of skeletal muscle from the lizard Sceloporus occidentalis with comments on methods for fitting and comparing force-velocity curves.

The isometric and isotonic contractile properties of fast-twitch glycolytic fibres of the iliofibularis muscle (FG-IF) in the lizard Sceloporus occidentalis were measured in vitro at 5 degrees C intervals form 10 to 40 degrees C. The mean isometric parameters at 35 degrees C, the preferred body temperature of this species, were as follows: maximum isometric force (Po), 187 +/- 8 (S.E.M.) kNm-2; ratio of twitch force to tetanic force (PTW/Po), 0.46 +/- 0.02; time to peak twitch tension (tPTW), 7.0 +/- 0.3 ms; and time from peak twitch force to 50% relaxation (t50% ), 8.2 +/- 0.3 ms. From 20 to 35 degrees C Po was almost constant (within 8% of the value at 35 degrees C). At 10 and 15 degrees C C. Po dropped to approximately 80% of the value at 35 degrees C. Po was very unstable at 40 degrees C. PTW/Po was almost constant at all temperatures. The time-related isometric parameters were positively modified by temperature at all temperatures measured (Q10 greater than 1.9). The force-velocity curves of the FG-IF deviated from the simple hyperbolic relation of A. V. Hill's characteristic equation. We present two alternative equations for fitting these data. These equations resulted in residual sums of squares from nonlinear least-squares analysis that were at least seven-fold lower than those from Hill's equation. The equation that best describes our data is a hyperbola modified by the addition of a linear component: V = B(1 - P/Po)/(A + P/Po) + C(1 - P/Po). To describe the curvature of this or any other force-velocity relationship, we propose the power ratio, Wmax/VmaxPo (where Wmax is the maximum power calculated from the force-velocity relationship and Vmax is the predicted maximum velocity of shortening at zero force). Vmax of the FG-IF was 21.9LoS-1 at 35 degrees C (where Lo is muscle length). This parameter was directly related to temperature between 10 and 35 degrees C with Q10 greater than 1.8. The shape of the force-velocity curve is not influenced by temperature (Wmax/VmaxPo = 0.11).

Animals↗

Thermal dependence of sprint performance of the lizard Sceloporus occidentalis.

Sprint velocity of the lizard Sceloporus occidentalis was maximal at preferred body temperature (Tb, 35 degrees C). Mean running velocity (VR) and stride frequency (f) at this temperature were 3.23 +/- 0.7 (mean +/- S.E.M.) ms-1 and 15.6 +/- 0.3 s-1, respectively. VR and f did not change significantly when Tb was raised to 40 degrees C. At Tb values between 25 and 35 degrees C the thermal dependencies of VR (Q10 = 1.23) and f (Q10 = 1.12) were quite low. At Tb values below 25 degrees C the thermal dependence of these factors increased markedly. Stride length (LS) was independent of Tb from 15 to 40 degrees C. Lizards with a Tb of 10 degrees C were largely incapacitated, and VR, f and LS were all greatly reduced. Comparisons with measurements of the contractile properties of skeletal muscle of this species suggest that stride frequency is limited by the twitch contraction time at temperatures below 23 degrees C. At higher temperatures, sprint performance is nearly independent of the thermal effects on the muscles.

Animals↗

Thermal dependence of isotonic contractile properties of skeletal muscle and sprint performance of the lizard Dipsosaurus dorsalis.

Contractile properties of the fast-twitch glycolytic (FG) portion of the iliofibularis muscle and sprint running performance were studied at approximately 5 degrees C intervals from 15-44 degrees C in the lizard Dipsosaurus dorsalis. Maximal running velocity (VR) and stride frequency (f) were both greatest when body temperature (Tb) was 40 degrees C, the field-active Tb in Dipsosaurus. At 40 degrees C VR was 4.3 +/- 0.2 m/s and f was 13.5 +/- 0.5 s-1. Between 25 and 40 degrees C, the thermal dependencies of VR and f were approximately constant (Q10's of 1.31 and 1.36 got VR and f, respectively). Below 25 degrees C performance declined more markedly with decreasing temperature. At 20 degrees C strides were qualitatively normal, but VR was only half of the value at 25 degrees C. At 15 degrees C the lizards were substantially incapacitated, and VR was 10% of the value at 20 degrees C. Stride length was approximately 0.33 m and changed very little with Tb from 20-44 degrees C. The time dependent contractile properties of FG muscle were affected more by temperature than was sprint performance. The maximal velocity of shortening at zero load (VO) was 18.7 0/s at 40 degrees C and had a Q10 of 1.7 from 25-40 degrees C. Maximal power output (Wmax) determined from the force-velocity curve was 464 W/kg at 40 degrees C. Below 40 degrees C max varied with temperature with a Q10 of 2-3. The shape of the force-velocity curve changed little with temperature (Wmax/POVO = 0.11). Between 25 and 40 degrees C a relatively temperature-independent process must modulate the effects of temperature on the contractile properties of the muscles that supply the power for burst locomotion. Storage and recovery of elastic energy appears to be a likely candidate for such a process. Below 25 degrees C, however, the contraction time is prolonged to such an extent that the f attainable is limited by the minimum time taken to contract and relax the muscles.

Animals↗

Critical importance of exposure duration for affective discrimination of stimuli that are not recognized.

Previous research has found that repeated exposure to briefly presented visual stimuli can increase the positive affect for the stimuli without enhancing their recognition. Subjects could discriminate target and distractor shapes by affective preference in the absence of recognition memory. This study examined this phenomenon as a function of stimulus exposure duration. Over exposure durations of 0, 2, 8, 12, 24, and 48 ms, the functions for affect and recognition judgments exhibited different temporal dynamics. Target selection by affect was possible at very brief exposures and was influenced little by increasing durations; target selection by recognition required longer stimulus exposures and improved with increasing durations. Affective discrimination of stimuli that are not recognized is a reliable phenomenon, but it occurs only within a narrow band of time. This parametric study has specified the relationship between exposure duration and affect and recognition judgments and has located that temporal window.

Adolescent↗

Metabolic adjustments of small passerine birds for migration and cold.

Passerines (members of the order Passeriformes such as finches, chickadees, jays, and warblers) are predominantly small birds characterized by relatively intense metabolic rates. Members of this group breeding at middle or high latitudes may either evade winter cold by migration or enhance their resistance to it by acclimatization. We review the energetic consequences associated with these two modes of response. Despite their apparent dissimilarity, migration and winter acclimatization both depend on substantial aerobic endurance, and both involve extensive power outputs by the flight muscles in locomotion or shivering. Such power outputs entail extensive deposition and catabolism of fat. Information available on these processes and their control in passerine birds is discussed. Knowledge of them is still in a formative stage, but it is already clear that aerobic capacity of passerines is stable at a high level throughout the year. However, changes are observed in the activity of certain enzymes involved in the catabolism of fats and carbohydrates. Full interpretation of these findings must await additional research. Nevertheless it is evident that the complex processes of migration and winter acclimatization are intimately linked with the metabolic properties of the highly aerobic skeletal muscle contained within the flight apparatus of passerines.

Acclimatization↗

Substrate metabolism in seasonally acclimatized American goldfinches.

Concentration of ([Glc]) and turnover (Ro) of plasma glucose, concentration of free fatty acids in plasma ([FFA]), and concentration of glycogen in muscle and liver were measured in freshly captured summer- and winter-acclimatized American goldfinches (Carduelis tristis). These birds were acutely exposed to one of three thermal regimes: 1) "thermoneutral," 30 degrees C in air, 2) "cold," -15 degrees C in air, and 3) "severe cold," 0 degrees C in 79% He and 21% O2. Additionally, the activities of citrate synthase (CS), phosphofructokinase (PFK), and beta-hydroxyacyl-CoA dehydrogenase (HOAD) were measured in pectoralis and leg muscles of winter and summer birds. Ro for goldfinches at 30 degrees C is unchanged between winter and summer, whereas it is 25% lower at -15 degrees C in winter than in summer birds, even though rates of heat production are similar. Additionally, winter animals depleted muscle glycogen at slower rates than summer individuals when exposed to "cold" or "severe cold." [Glc] and [FFA] for each test regime did not vary between seasons. The activity of the beta-oxidative enzyme HOAD is the pectoralis muscle (the main thermogenic tissue) increases by 50% from summer to winter, but the activities of PFK and CS remain essentially constant. We conclude that the ability to restrict carbohydrate use under cold stress is a component of the winter acclimatization process in the American goldfinch. One mechanism which might foster this ability in the increase in beta-oxidative capacity of the flight muscles, permitting a greater reliance on fatty acids by winter animals during cold-induced thermogenesis.

3-Hydroxyacyl CoA Dehydrogenases↗