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Inner arm dynein ATPase fraction of sea urchin sperm flagella causes active sliding of axonemal outer doublet microtubule.

In order to clarify the role of the inner arms of the axoneme in sperm flagellar movement, we prepared an ATPase fraction (12S) from the outer arm-depleted axonemes of sea urchin sperm flagella. When both arm-depleted axonemes were incubated with the 12S ATPase, they exhibited the sliding disintegration of outer doublet microtubules. Electron microscopy revealed that the ATPase rebound to the original inner arm sites of the axoneme. Therefore, it is quite likely that the 12S ATPase is one of the components of the inner arms. We referred to it as "inner arm dynein".

Animals↗

Chemical decoupling of ATPase activation and force production from the contractile cycle in myosin by steric hindrance of lever-arm movement.

The myosin motor protein generates force in muscle by hydrolyzing Adenosine 5'-triphosphate (ATP) while interacting transiently with actin. Structural evidence suggests the myosin globular head (subfragment 1 or S1) is articulated with semi-rigid catalytic and lever-arm domains joined by a flexible converter domain. According to the prevailing hypothesis for energy transduction, ATP binding and hydrolysis in the catalytic domain drives the relative movement of the lever arm. Actin binding and reversal of the lever-arm movement (power stroke) applies force to actin. These domains interface at the reactive lysine, Lys84, where trinitrophenylation (TNP-Lys84-S1) was observed in this work to block actin activation of myosin ATPase and in vitro sliding of actin over myosin. TNP-Lys84-S1's properties and interactions with actin were examined to determine how trinitrophenylation causes these effects. Weak and strong actin binding, the rate of mantADP release from actomyosin, and actomyosin dissociation by ATP were equivalent in TNP-Lys84-S1 and native S1. Molecular dynamics calculations indicate that lever-arm movement inhibition during ATP hydrolysis and the power stroke is caused by steric clashes between TNP and the converter or lever-arm domains. Together these findings suggest that TNP uncouples actin activation of myosin ATPase and the power stroke from other steps in the contraction cycle by inhibiting the converter and lever-arm domain movements.

Actins↗

Male mice exhibit better spatial working and reference memory than females in a water-escape radial arm maze task.

The present study examined sex differences in spatial working and reference memory in C57BL/6 mice. Males and females were tested in a version of the spatial 8-arm radial arm maze in which the motivating stimulus was escape from water. To test spatial working memory, four arms were baited with submerged escape platforms, each of which was removed after it was found. Four arms that never contained platforms assessed spatial reference memory. In addition to determining the number of working memory and reference memory errors made in each session, working memory errors made in each trial were analyzed to examine performance as the number of arms to be remembered (i.e. the working memory load) increased. Males committed significantly fewer working memory and reference memory errors than females throughout testing. Within a session, males committed fewer working memory errors than females as the working memory load increased. These sex differences were particularly evident during task acquisition. The data indicate that male C57BL/6 mice learn both the working and reference memory components of a water-escape motivated radial arm maze task better than female mice.

Animals↗

In vivo measurement-based estimations of the moment arm in the human tibialis anterior muscle-tendon unit.

The aim of this study was to estimate the moment arm of human tibialis anterior (TA) muscle-tendon unit at rest and during isometric dorsiflexion maximum voluntary contraction (MVC) from in vivo sagittal-plane magnetic resonance (MR) and ultrasound scans. Two methods were employed, both of them based on the assumption that the ankle joint complex and TA muscle-tendon unit operate in the sagittal plane. Using method A, moment arms were obtained from MR scans of the foot by measuring the perpendicular distance between a moving centre of rotation in the talo-crural joint and the TA tendon action line. Using method B, moment arms were calculated from the ratio of TA tendon displacement, which was estimated from a planimetric muscle model using pennation angles and muscle thickness measured by ultrasonography, to the tibial rotation around the talus, which was measured from the foot MR scans. Using either of the two methods at rest, the estimated TA moment arm decreased from approximately 4.5 to approximately 2.9 cm in the transition from dorsiflexion to plantarflexion. Using method A, moment arms during MVC were larger by 0.9-1.5 cm (33-44%, P < 0.01) than the respective resting estimations. In contrast, no difference (P > 0.05) was found between the resting and MVC moment arm estimations of method B. Limitations in the oversimplified musculoskeletal model used raise questions for the validity of both method estimations.

Adult↗

Limitations of using outcomes in the placebo arm of a clinical trial of benign prostatic hyperplasia to quantify those in the community.

OBJECTIVES: To quantify potential biases that may occur when placebo arms of clinical trials are used to characterize the natural history of disease and to compare incidence rates of benign prostatic hyperplasia (BPH) outcomes in community-dwelling men with outcomes in the placebo arm of a clinical trial of BPH. SUBJECTS AND METHODS: White men aged 50 years or older at baseline were selected randomly from the Olmsted County, Minnesota, community in 1990 and were monitored biennially through 1996 for urologic outcomes. Symptom progression, acute urinary retention, and minimally Invasive or surgical treatment of BPH were assessed from a validated questionnaire and a review of community medical records. Findings from the Olmsted County Study (N=1193) and a selected subcohort (n=238) were compared with those from the placebo arm of the Medical Therapy of Prostatic Symptoms trial (N=737). RESULTS: During more than 5088 person-years of follow-up (mean, 4.9 years) In the Olmsted County Study, Incidence rates per 1000 person-years were 8.5 (95% confidence Interval [CI], 6.4-11.2) for acute urinary retention, 97.1 (95% CI, 88.7-106.0) for symptom progression, 6.6 (95% CI, 4.8-9.0) for surgery or minimally invasive treatment, and 105.1 (95% CI, 96.4-114.4) for any outcomes for all men. For those meeting trial Inclusion criteria (selected subcohort, n=238), Incidence rates were 18.3, 86.5, 16.8, and 109.4, respectively. By comparison, Incidence rates per 1000 person-years for the placebo arm of the Medical Therapy of Prostatic Symptoms clinical trial for BPH (mean follow-up, 4.5 years) were 6 for acute urinary retention, 36 for symptom progression, and 45 for any outcome, but the estimate of 13 for surgery or minimally invasive treatment was higher than for men in the Olmsted County Study. CONCLUSIONS: Compared with community-dwelling men, men in the placebo arm of this clinical trial of BPH treatments had a substantially lower risk of BPH-related outcomes. Extrapolation of findings from the placebo arm of clinical trials to describe the natural history of disease in community-dwelling men should be done with caution and appropriate recognition of limitations.

Adult↗

[Changes in knee kinematics and quadriceps and hamstrings moment arms after high valgus and varus tibial "dome" osteotomy: An in vitro study].

PURPOSE OF THE STUDY: Analysis of the correction or over-correction of high valgus and varus tibial osteotomies is generally limited to the frontal plane. Most likely however, the deformation observed radiographically in the frontal plane is simply a one-dimensional expression of a more complex three-dimensional deformation. This might be one of the causes for certain failures after surgery and recurrent problems which are difficult to solve. We proposed using 3D electrogoniometric to measure of the effect of a "dome" osteotomy on patellar and femoro-tibial kinematics and the changes in the moment arms of the knee muscles. MATERIAL AND METHODS: We used five lower limbs harvested from non-fixed cadavers. A "dome" osteotomy was stabilized by external fixation. Three-dimensional analysis of the femoro-tibial and femoro-patellar kinematics was performed using two electrogoniometers with six degrees of freedom. Changes in the lengths of the hamstrings and quadriceps was measured using four LVDT linear variable differential transformers. The muscles lever arms were measured with the tendon excursion method. RESULTS: At 90 degrees flexion, varus osteotomy induced internal rotation while valgus osteotomy induced the opposite effect. Beyond 40 degrees flexion, there was a clear internal rotation of the patella for varus and neutral corrections. Valgus corrections however induced external rotation. The peak lever arm of the quadriceps increased with valgus, while the angle of the peak was higher for varus correction. Valgus appeared to increase the lever arm of the semitendinous. DISCUSSION: Our study demonstrated that the effect of tibial osteotomy is not limited to the frontal plane. Tibial rotations are observed systematically for all corrections in the frontal plane. Varus correction tends to create internal rotation while valgus correction tends to have the opposite effect. Axial correction also affects patellar kinematics. Interanal rotation is induced by varus correction and external rotation by valgus correction. This patellar rotation could result from tibial rotations induced by the different corrections. The loss of the parallelism between the patellar crest and the trochlear groove could produce changes in femoropatellar surface contact and pressure, potentially leading to pain or cartilage degeneration. The maximal value of the quadriceps moment arm appears to increase with valgus. The efficacy of the quadriceps could thus be improved with valgus, potentially increasing extension force. Valgus increases the moment arm, improving limb flexion, while varus correction has the opposite effect. This could explain a loss in flexion amplitude in patients with varus or who underwent varus osteotomy. Tibial osteotomy is designed to correct the deviation solely in the frontal plane but also has effects in all three planes. Further 3D analyses of the morphology and physiology of the knee joint would be needed to better understand the physiological and pathological processes involved.

Biomechanical Phenomena↗

An international classification and grading system for age-related maculopathy and age-related macular degeneration. The International ARM Epidemiological Study Group.

A common detection and classification system is needed for epidemiologic studies of age-related maculopathy (ARM). Such a grading scheme for ARM is described in this paper. ARM is defined as a degenerative disorder in persons > or = 50 years of age characterized on grading of color fundus transparencies by the presence of the following abnormalities in the macular area: soft drusen > or = 63 microns, hyperpigmentation and/or hypopigmentation of the retinal pigment epithelium (RPE), RPE and associated neurosensory detachment, (peri)retinal hemorrhages, geographic atrophy of the RPE, or (peri)retinal fibrous scarring in the absence of other retinal (vascular) disorders. Visual acuity is not used to define the presence of ARM. Early ARM is defined as the presence of drusen and RPE pigmentary abnormalities described above; late ARM is similar to age-related macular degeneration (AMD) and includes dry AMD (geographic atrophy of the RPE in the absence of neovascular AMD) or neovascular AMD (RPE detachment, hemorrhages, and/or scars as described above). Methods to take and grade fundus transparencies are described.

Aged↗

Context-dependent arm pointing adaptation.

We sought to determine the effectiveness of head posture as a contextual cue to facilitate adaptive transitions in manual control during visuomotor distortions. Subjects performed arm pointing movements by drawing on a digitizing tablet, with targets and movement trajectories displayed in real time on a computer monitor. Adaptation was induced by presenting the trajectories in an altered gain format on the monitor. The subjects were shown visual displays of their movements that corresponded to either 0.5 or 1.5 scaling of the movements made. Subjects were assigned to three groups: the head orientation group tilted the head towards the right shoulder when drawing under a 0.5 gain of display and towards the left shoulder when drawing under a 1.5 gain of display; the target orientation group had the home and target positions rotated counterclockwise when drawing under the 0.5 gain and clockwise for the 1.5 gain; the arm posture group changed the elbow angle of the arm they were not drawing with from full flexion to full extension with 0.5 and 1.5 gain display changes. To determine if contextual cues were associated with display alternations, the gain changes were returned to the standard (1.0) display. Aftereffects were assessed to determine the efficacy of the head orientation contextual cue compared to the two control cues. The head orientation cue was effectively associated with the multiple gains. The target orientation cue also demonstrated some effectiveness while the arm posture cue did not. The results demonstrate that contextual cues can be used to switch between multiple adaptive states. These data provide support for the idea that static head orientation information is a crucial component to the arm adaptation process. These data further define the functional linkage between head posture and arm pointing movements.

Adult↗

Previous maze experience required to increase open arms avoidance in rats submitted to the elevated plus-maze model of anxiety.

Studies have shown an increased open arm avoidance in rats re-exposed to the elevated plus-maze (EPM), which suggests a qualitative shift in emotional states from an unconditioned (Trial 1) to a learned (Trial 2) form of fear response, but a precise source of aversion has not been determined. Using rats submitted to the EPM or various EPM-derived configurations, this study was designed to investigate what previous maze experiences in Trial 1 are required to increase avoidance of open arms in EPM Trial 2. Results obtained from rats submitted to the EPM or EPM-derived configurations confirmed the increased open arms avoidance in Trial 2. Rats confined to either open or enclosed arms failed to show the increased avoidance of open arms in Trial 2. The results are discussed in terms of the minimum prerequisite in Trial 1 to elicit an avoidance learning response to open arms in Trial 2, and also the implications of an acquired fear response in rats for the study of the biological basis of anxiety.

Animals↗

Effects of social facilitation for locating feeding sites by cattle in an eight-arm radial maze.

A study was conducted in an eight-arm radial maze to determine if cattle with various foraging experiences could facilitate location of feeding sites by other cattle. Heifers assigned as "followers" (n=24) were initially trained to expect straw at the end of each arm. Initial training of heifers assigned as "leaders" (n=12) differed based on the three following treatments:(1) no-experience, (2) barley in the same two arms, and (3) barley in two arms but locations changed daily. During training, leaders with barley in fixed locations foraged more efficiently by traveling to fewer (P<0.05) arm ends to find barley than leaders in the variable treatment. After training, two followers were placed in the maze with a leader, and barley was available in two arms. Leaders facilitated the location of barley by followers. In 61% of the occasions that followers first found barley, leaders were at the feeding site. Eighty-one percent of followers later located barley without leaders in the maze. Followers with experienced leaders did not find barley consistently more often than heifers with inexperienced leaders. Cattle can apparently learn feeding site locations from other animals, but additional research is needed to evaluate the behavioral mechanisms that influence social facilitation during foraging.

Journal Article↗

The use of 'arms-length' organizations for health system change in Ontario, Canada: some observations by insiders.

During the past decade, there has been substantial health system reform in the United States, United Kingdom, New Zealand, and many other countries. For the most part, Canada has not pursued 'big bang' health system change but rather a variety of strategies to achieve incremental change. In this paper, we present the ways in which three arms-length organizations have been used by government to effect incremental system change in Ontario during the past several years. We observe that, (1) the influence of politics and political interference can be reduced through an arms-length organization; (2) an arms-length organization with the power to make decisions entails more political risk for government and encounters more scrutiny and criticism by providers and the media than an organization with the power to recommend only; (3) an arms-length organization with a limited lifespan faces more delaying tactics by adversely affected parties than an organization without a limited lifespan; (4) an arms-length organization with perceived influence may attract causes that are not related to its mandate; (5) the importance and difficulty of communicating complex information about system change to a wide variety of audiences cannot be overstated; (6) system change informed by the use of expert opinion encounters less provider resistance and may result in better decisions; and (7) the reputation of the Chair and the perceived competence and experience of the CEO are critical success factors in the success of an arms-length organization.

Cardiac Care Facilities↗

Wrist kinetics after luno-triquetral dissociation: the changes in moment arms of the flexor carpi ulnaris tendon.

Wrist biomechanics after luno-triquetral (LT) dissociation is important for understanding the clinical sequelae of the disease and for determining its treatment options. The LT interosseous ligament plays an important role in stabilizing the joint and damage to the ligament would be expected to significantly increase moment arms of tendon of the flexor carpi ulnaris (FCU), the principal ulnar wrist flexor. We investigated the changes in moment arms of FCU tendon after various amounts of sectioning of the ligaments proven to be associated with LT dissociation. In six fresh frozen cadaveric upper extremities, excursions of the FCU tendon were recorded simultaneously with wrist joint angulation during wrist flexion-extension and radioulnar deviation. Tendon excursions were measured in intact wrists, in wrists with sectioning of the dorsal portion of the LT interosseous ligament, in wrists with sectioning of the entire LT interosseous ligament, and finally in wrists with further sectioning of the dorsal radiotriquetral and intercarpal ligaments. Moment arms of the tendon were calculated from tendon excursions and joint motion angulations and expressed as percentage changes from those in the intact wrist. During wrist flexion-extension, moment arms of the FCU tendon after sectioning of the entire LT interosseous ligament and after sectioning of the two capsular ligaments were 112 +/- 7% and 114 +/- 8%, respectively; these values were significantly greater than those in the intact wrist. During radioulnar deviation, the moment arms were 114 +/- 11% after sectioning of the dorsal portion of the LT interosseous ligament, 134 +/- 15% after sectioning of the entire ligament, and 153 +/- 18% after sectioning of the capsular ligaments, again being significantly greater than the normal wrist. Increase in moment arms of the FCU tendon after loss of integrity of the LT interosseous ligament and dorsal capsular ligaments may contribute to clinical sequelae of LT dissociation and difficulty in treating this disorder.

Adult↗

Neural control of rhythmic arm movements.

In this paper we present an approach to robot arm control based on exploiting the dynamical properties of a simple neural network oscillator circuit coupled to the joints of an arm. The entrainment and input/output properties of the oscillators are used to perform a variety of tasks with the same architecture, without any modeling of the arm or its environment. The approach is implemented on two real robot arms, and has been used to tune into the resonant frequency of pendulums, perform multi-joint coordinated motion by turning cranks, and exploit the dynamics of a 'Slinky' toy to coordinate the motion of two arms. By exploiting the coupling between the physical arm and the neural oscillator, a range of complex behaviors can be achieved with a very simple system.

Journal Article↗

Proline-dependent oligomerization with arm exchange.

BACKGROUND: Oligomerization is often necessary for protein activity or regulation and its efficiency is fundamental for the cell. The quaternary structure of a large number of oligomers consists of protomers tightly anchored to each other by exchanged arms or swapped domains. However, nothing is known about how the arms can be kept in a favourable conformation before such an oligomerization. RESULTS: Upon examination of such quaternary structures, we observe an extremely frequent occurrence of proline residues at the point where the arm leaves the protomer. Sequence alignment and site-directed mutagenesis confirm the importance of these prolines. The conservation of these residues at the hinge regions can be explained by the constraints that they impose on polypeptide conformation and dynamics: by rigidifying the mainchain, prolines favour extended conformations of arms thus favouring oligomerization, and may prevent interaction of the arms with the core of the protomer. CONCLUSIONS: Hinge prolines can be considered as 'quaternary structure helpers'. The presence of a proline should be considered when searching for a determinant of oligomerization with arm exchange and could be used to engineer synthetic oligomers or to displace a monomers to oligomers equilibrium by mutation of this proline residue.

Acetyltransferases↗

The RSC nucleosome-remodeling complex is required for Cohesin's association with chromosome arms.

The fidelity of chromosome segregation requires that the cohesin protein complex bind together newly replicated sister chromatids both at centromeres and at discrete sites along chromosome arms. Segregation of the yeast 2 micro plasmid also requires cohesin, which is recruited to the plasmid partitioning locus. Here we report that the RSC chromatin-remodeling complex regulates the differential association of cohesin with centromeres and chromosome arms. RSC cycles on and off chromosomal arm and plasmid cohesin binding sites in a cell cycle-regulated manner 15 min preceding Mcd1p, the central cohesin subunit. We show that in rsc mutants Mcd1p fails to associate with chromosome arms but still binds to centromeres, and that consequently, the arm regions of mitotic sister chromosomes separate precociously while cohesion at centromeres is unaffected. Our data suggest a role for RSC in facilitating the loading of cohesin specifically onto chromosome arms, thereby ensuring sister chromatid cohesion and proper chromosome segregation.

Binding Sites↗

A longitudinal study of growth patterns in schoolchildren in one Taipei District. II: Sitting height, arm span, body mass index and skinfold thickness.

BACKGROUND: It has been suggested that longitudinal rather than cross-sectional growth standards be used to assess individual growth patterns. Thus, the aim of this study was to follow boys and girls throughout their pubertal years, so that a mixed longitudinal growth curve of height, weight, sitting height, arm span, skinfold thickness, body mass index (BMI), and the ratio of sitting height or arm span to stature, could be obtained. METHODS: A defined group of 1,139 healthy schoolchildren (570 boys and 569 girls) from the Shih-Pai district of Taipei were followed longitudinally for 4 years. Anthropometric measurements of height, weight, sitting height, arm span, skinfold thickness, and BMI, were obtained for each child. RESULTS: Peak sitting-height velocities of 6.1 cm/year (boys) and 6.3 cm/year (girls) were seen at 8.5 years. The second peak of sitting-height velocity occurred at a mean age of 12.5 years for boys and 11.5 years for girls. Sitting-height velocity for the whole year covering the second peak was 4.6 cm in boys and 3.2 cm in girls. Peak arm-span velocity was seen at 13.5 years for boys and 8.5 years for girls, and arm-span velocity for the whole year covering this peak was 8.4 cm/year for boys and 8.1 cm/year for girls. CONCLUSION: These data provide growth patterns for Chinese children aged 8-18 years living in a Taipei district, with percentile charts for sitting height, arm span, BMI, and skinfold thickness.

Adolescent↗

Effect of spacer arm length on protein retention on a strong cation exchange adsorbent.

The retention of five proteins was compared on a set of three strong cation exchange adsorbents that differed in spacer arm chemical structure and length. The adsorbents included a commercial product, Amersham Biosciences SP Sepharose Fast Flow, containing a six-carbon spacer between the agarose matrix and the anionic ligand, and two custom-prepared materials. One of the custom adsorbents contained a spacer of about half the length of the SP Sepharose Fast Flow, and the other contained no spacer arm. The adsorbent with no spacer arm was found to be significantly more retentive for all of the test proteins examined, in both isocratic and gradient elution tests. Reducing the spacer arm length by half resulted in increased retention for four of the five proteins, but this increase was less than what was observed when the spacer arm was eliminated. Retention increases were obtained without increasing the density of the anionic charge groups and appear to result from an enhancement of electrostatic or secondary nonelectrostatic interactions, or both. The results indicate that spacer arm length may be a useful variable in manipulating stationary-phase retention properties.

Adsorption↗

Myosin motor domain lever arm rotation is coupled to ATP hydrolysis.

We have investigated coupling of lever arm rotation to the ATP binding and hydrolysis steps for the myosin motor domain. In several current hypotheses of the mechanism of force production by muscle, the primary mechanical feature is the rotation of a lever arm that is a subdomain of the myosin motor domain. In these models, the lever arm rotates while the myosin motor domain is free, and then reverses the rotation to produce force while it is bound to actin. These mechanical steps are coupled to steps in the ATP hydrolysis cycle. Our hypothesis is that ATP hydrolysis induces lever arm rotation to produce a more compact motor domain that has stored mechanical energy. Our approach is to use transient electric birefringence techniques to measure changes in hydrodynamic size that result from lever arm rotation when various ligands are bound to isolated skeletal muscle myosin motor domain in solution. Results for ATP and CTP, which do support force production by muscle fibers, are compared to those of ATPgammaS and GTP, which do not. Measurements are also made of conformational changes when the motor domain is bound to NDP's and PP(i) in the absence and presence of the phosphate analogue orthovanadate, to determine the roles the nucleoside moieties of the nucleotides have on lever arm rotation. The results indicate that for the substrates investigated, rotation does not occur upon substrate binding, but is coupled to the NTP hydrolysis step. The data are consistent with a model in which only substrates that produce a motor domain-NDP-P(i) complex as the steady-state intermediate make the motor domain more compact, and only those substrates support force production.

Adenosine Triphosphate↗