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At least 163 records · Page 9Linked to original sources

PubMed2006

Exploration of the conformational space of myosin recovery stroke via molecular dynamics.

Muscle contractions are driven by cyclic conformational changes of myosin, whose molecular mechanisms of operation are being elucidated by recent advances in crystallographic studies and single molecule experiments. To complement such structural studies and consider the energetics of the conformational changes of myosin head, umbrella sampling molecular dynamics (MD) simulations were performed with the all-atom model of the scallop myosin sub-fragment 1 (S1) with a bound ATP in solution in explicit water using the crystallographic near-rigor and transition state conformations as two references. The constraints on RMSD reaction coordinates used for the umbrella sampling were found to steer the conformational changes efficiently, and relatively close correlations have been observed between the set of characteristic structural changes including the lever arm rotation and the closing of the nucleotide binding pocket. The lever arm angle and key residue interaction distances in the nucleotide binding pocket and the relay helix show gradual changes along the recovery stroke reaction coordinate, consistent with previous crystallographic and computational minimum energy studies. Thermal fluctuations, however, appear to make the switch-2 coordination of ATP more flexible than suggested by crystal structures. The local solvation environment of the fluorescence probe, Trp 507 (scallop numbering), also appears highly mobile in the presence of thermal fluctuations.

Animals↗

PubMed2004

Predator-driven phenotypic diversification in Gambusia affinis.

Predation is heterogeneously distributed across space and time, and is presumed to represent a major source of evolutionary diversification. In fishes, fast-starts--sudden, high-energy swimming bursts--are often important in avoiding capture during a predator strike. Thus, in the presence of predators, we might expect evolution of morphological features that facilitate increased fast-start speed. We tested this hypothesis using populations of western mosquitofish (Gambusia affinis) that differed in level of predation by piscivorous fish. Body morphology of G. affinis males, females, and juveniles diverged in a consistent manner between predatory environments. Fish collected from predator populations exhibited a larger caudal region, smaller head, more elongate body, and a posterior, ventral position of the eye relative to fish from predator-free populations. Divergence in body shape largely matched a priori predictions based on biomechanical principles, and was evident across space (multiple populations) and time (multiple years). We measured maximum burst-swimming speed for male mosquitofish and found that individuals from predator populations produced faster bursts than fish from predator-free populations (about 20% faster). Biomechanical models of fish swimming and intrapopulation morphology-speed correlations suggested that body shape differences were largely responsible for enhanced locomotor performance in fish from predator populations. Morphological differences also persisted in offspring raised in a common laboratory environment, suggesting a heritable component to the observed morphological divergence. Taken together, these results strongly support the hypothesis that divergent selection between predator regimes has produced the observed phenotypic differences among populations of G. affinis. Based on biomechanical principles and recent findings in other species, it appears that the general ecomorphological model described in this paper will apply for many aquatic taxa, and provide insight into the role of predators in shaping the body form of prey organisms.

Analysis of Variance↗

PubMed2005

Understanding and measuring powered wheelchair mobility and manoeuvrability. Part I. Reach in confined spaces.

PURPOSE: To determine: (1) what wheelchair manoeuvrability factors are important and (2) the effects of powered wheelchair design on the ability to reach in a confined space. METHOD: The relative importance of five aspects of wheelchair manoeuvrability was determined through a survey of users of wheelchairs (N = 52) and health care professionals and others (N = 89). A single young, non-disabled subject undertook repeated trials of reach distance on to a counter at the end of a corridor whose width could be adjusted by moving Styrofoam walls. RESULTS: Reaching, moving in confined spaces and avoiding collisions were more important than speed and avoiding the need to drive backwards. The rear wheel drive powered wheelchair was found to allow the greatest reach when driving backwards into the space and the wheelchair which moved in a sideways direction allowed greatest reach in the narrowest corridor. CONCLUSIONS: The survey concluded that manoeuvring in small spaces and reaching without collisions were important. The powered wheelchair with sideways capability afforded the greatest reach in confined spaces except when the rear wheel drive chair was driven in backwards. The survey respondents did not place a high priority on avoiding backwards driving but some people find this difficult to do safely.

Comprehension↗

PubMed2002

[Respiratory distress. New Perspectives to lung edema treatment].

Acute respiratory distress syndrome (ARDS) is a life threatening condition associated with great morbidity and mortality. it is characterized initially by accumulation of fluid in the alveolar space that impairs alveolar oxygen exchange. Eventually, this syndrome leads to multiorgan failure. Therefore, rapid edema clearance has generally been associated with better outcome in patients with acute respiratory distress syndrome. Clearance of alveolar fluid is driven predominantly by active Na+ transport out of the alveolar space, mediated by increased apical Na(+)-channel and Na-K-ATPase activity. It has been demonstrated that increases in Na-K-ATPase in response to catecholamines in the alveolar epithelium are associated with increased lung edema clearance. The cellular mechanisms involve the recruitment of new Na-K-ATPase molecules to the plasma membrane from intracellular organelles. It also appears that adenovirus-mediated Na-K-ATPase gene transfer and increased Na-K-ATPase expression may provide an alternative and efficient pathway for transient increase in alveolar fluid reabsorption and resolution of pulmonary edema.

Catecholamines↗

PubMed2005

Molecular principles of hair follicle induction and morphogenesis.

Hair follicle (HF) development is the result of neuroectodermal-mesodermal interactions, and can be divided into morphologically distinguishable stages (induction, organogenesis and cytodifferentiation). The spacing, polarity and differentiation patterns of HFs are driven by interacting, self-assembling gradients of inhibitors and activators, which are established jointly by the skin epithelium and mesenchyme. For HF development to occur, the dominant-negative influence of inhibitors of the HF differentiation pathway must be locally counteracted by specific antagonists and/or overriden by stimulators of hair placode formation. Once a mesenchymal condensate of inductive fibroblasts has formed, it takes over control of most subsequent steps of HF organogenesis and of epithelial stem cell differentiation into distinct lineages. In this review we introduce the morphological characteristics, major underlying principles and molecular key players that control HF development. The focus is on recent insights into the molecular interactions leading to hair follicle induction, and we close with synthesizing a corresponding working hypothesis.

Animals↗

PubMed1993

Theoretical reconstruction of myotonia and paralysis caused by incomplete inactivation of sodium channels.

Muscle fibers from individuals with hyperkalemic periodic paralysis generate repetitive trains of action potentials (myotonia) or large depolarizations and block of spike production (paralysis) when the extracellular K+ is elevated. These pathologic features are thought to arise from mutations of the sodium channel alpha subunit which cause a partial loss of inactivation (steady-state Popen approximately 0.02, compared to < 0.001 in normal channels). We present a model that provides a possible mechanism for how this small persistent sodium current leads to repetitive firing, why the integrity of the T-tubule system is required to produce myotonia, and why paralysis will occur when a slightly larger proportion of channels fails to inactivate. The model consists of a two-compartment system to simulate the surface and T-tubule membranes. When the steady-state sodium channel open probability exceeds 0.0075, trains of repetitive discharges occur in response to constant current injection. At the end of the current injection, the membrane potential may either return to the normal resting value, continue to discharge repetitive spikes, or settle to a new depolarized equilibrium potential. This after-response depends on both the proportion of noninactivating sodium channels and the magnitude of the activity-driven K+ accumulation in the T-tubular space. A reduced form of model is presented in which a two-dimensional phase-plane analysis shows graphically how this diversity of after-responses arises as extracellular [K+] and the proportion of noninactivating sodium channels are varied.

Animals↗

PubMed2000

Correlation between remaining length of root canal fillings after immediate post space preparation and coronal leakage.

The seal provided by root canal fillings after post space preparation was studied using a pressure-driven radioactive tracer assay. The coronal part of root canal fillings was immediately removed, using a hot plugger, to a remaining length of either 3, 5, 7, or 9 mm. Intact root canal fillings of 14 mm served as control. Application of air pressure of 130 mm Hg to the tracer solution drove it through the fillings and into phosphate-buffered saline surrounding the apex. Leakage gradually increased for 28 days, and differences in the leakage through 3 to 9 mm fillings were demonstrated. In a passive system by which an additional group of teeth were tested none of these differences could be detected. It was concluded that: (a) root canal fillings of 3, 5, and 7 mm have an inferior seal, compared with that of an intact filling; (b) the sealing is proportional to the length of the remaining filling; and (c) a passive system is unable to detect these differences, even when conducted for as long as 28 days.

Analysis of Variance↗

PubMed1992

Bidirectional peritoneal transport of immunoglobulin in rats: compartmental kinetics.

Protein transport to and from fluid in the peritoneal cavity is observed during clinical procedures. Dialysate osmolality is a major determinant of net fluid flux into the cavity. We carried out experiments in rats to determine the plasma, peritoneal, and tissue concentrations of immunoglobulin (Ig) G resulting from either intravenous (iv) or intraperitoneal (ip) administration during hypertonic or isotonic dialyses. After iv injection of IgG, overall mass transfer into the cavity was not affected by the osmolality. After ip injection, tissue concentrations were dependent on the dialysis duration. Protein absorption from the hypertonic dialysate into the surrounding tissue was quantitatively less than the absorption from an isotonic dialysis solution at 20 min. By 200 min, total protein transport was not affected by dialysate osmolality. Lymphatic transport to the plasma amounted to 20-25% of the total protein loss from the peritoneal cavity; approximately 60% of the absorbed dose was found in tissues surrounding the cavity at both 20 and 200 min, with particularly high concentrations in parietal areas. We conclude that immunoglobulin transport in the peritoneal tissue, resulting from either iv or ip injection, is influenced by route of administration but is little affected by dialysate osmolality. Peritoneal absorption of proteins occurs directly into the surrounding tissue interstitial space as a result of hydrostatic pressure-driven convection and diffusion.

Absorption↗

PubMed1994

Three-dimensional display in the evaluation and performance of neurosurgery without a stereotactic frame: more than a pretty picture?

Display of three-dimensionally rendered images derived from radiological data sets is often suggested to be useful for surgical and radiation treatment planning in neurosurgery. Nevertheless, physicians will often note (off the record) that these rendered images are 'just a pretty picture' and are not clinically useful. This paper will discuss our three-dimensional rendering and quantitative analysis software and its primary use in evaluating and utilizing frameless stereotactic methodologies. A variety of concepts and techniques will be discussed. Specifically, a computer graphic and statistical-based technique will be presented that enables timely and measurable image registration between radiological image space and the coordinate system of computer-driven surgical devices in the operating room. This technique may be utilized to maintain a surgeon's orientation and to quantitatively and graphically monitor the position of probes and instruments in the surgical field. Three-dimensional quantitative results of phantom testing will be presented. Correlation to and validation against stereotactic imaging calculations using the compass stereotactic system will also be discussed. These computer graphic/statistical-based techniques are applicable for evaluating the accuracy of any frameless stereotactic device including, but not limited to robotic arms, spark gap, LED and magnetic field digitizers.

Evaluation Studies as Topic↗

PubMed1987

Intestinal maturation: calcium transport by basolateral membranes.

The overall characteristics of calcium transport across the intestine have been defined using in vivo perfusion techniques and in vitro everted gut sacs. However, calcium transport represents three separate processes: entry at the brush border membranes, movement across the cytoplasm, and exit at the basolateral membranes (BLM). Studies in adult animals indicated that the active step in calcium transport is located at the BLM. The present studies describe for the first time the maturational aspects of calcium transport across the BLM of the enterocyte. We utilized a percoll density gradient to prepare enriched BLMs from suckling and adolescent rats. Calcium uptake into BLMs represented mainly transport into the intravesicular space. Calcium transport in both age groups was driven by ATP; the calcium transport in the presence and absence of ATP was significantly greater in suckling rats compared to adolescent rats. Kinetics of calcium uptake calculated from uptake values in the presence of ATP minus no ATP conditions showed a Km of 0.06 +/- 0.01 and 0.03 +/- 0.01 microM for adolescent and suckling rats respectively (p less than 0.05). Vmax was 1.5 +/- 0.1 and 0.8 +/- 0.08 nmol/mg protein/min for adolescent and suckling rats respectively (p less than 0.01). Calcium/sodium exchange mechanisms was also present in both age groups. However, the magnitude of sodium-dependent calcium exchange was smaller in suckling rats compared to adolescent rats. These data suggest that calcium exit at the BLMs of enterocytes of suckling and adolescent rats occurs by an ATP-dependent and a calcium/sodium exchange mechanism. Both mechanisms exhibit maturational changes.

Adenosine Triphosphate↗

PubMed1995

New developments in patient-controlled postoperative analgesia.

Patient-controlled analgesia (PCA) is a newer technique for pain management. Patients are allowed to self-administer small analgesic bolus doses into a running intravenous infusion, intramuscularly, subcutaneously or even into the epidural space. Demands are usually controlled by computer-driven infusion pumps, but can also be delivered by disposable devices. Clinical experience demonstrates that individual variability in pain sensitivity and analgesic needs are of utmost importance. In contrast to earlier expectations, opioid consumption is usually higher than with restrictive conventional dosing regimes, but without an increase in serious side effects. Patients' acceptance is generally enthusiastic because of the possibility of self-control. PCA has proved its importance for pain studies, e.g. for algesimetry, to determine predictors of postoperative pain, to describe drug interactions, to evaluate the concept of pre-emptive analgesia or for pharmacokinetic designs. It is concluded that PCA results have been urgently required in order to change the mind of physicians and nursing staff with respect to individual pain management strategies. Once this goal is achieved, PCA concepts should also be used for the improvement of more conventional techniques.

Analgesia, Patient-Controlled↗

PubMed2006

Tick-borne disease systems: mapping geographic and phylogenetic space.

Evidence is presented that the evolution of the tick-borne flaviviruses is driven by biotic factors, principally the exploitation of new hosts as transmission routes. Because vector-borne diseases are limited by climatic conditions, however, abiotic factors have the potential to direct and constrain the evolutionary pathways. This idea is explored by testing the hypothesis that closely related viruses occupy more similar eco-climatic spaces than do more distantly related viruses. A statistical comparison of the conventional phylogenetic tree derived from molecular distances and a novel phenetic tree derived from distances between the climatic spaces within which each virus circulates, indicates that these trees match each other more closely than would be expected at random. This suggests that these viruses are indeed limited in the degree to which they can evolve into new environmental conditions.

Animals↗

PubMed2006

Spiders: water-driven erosive structures in the southern hemisphere of Mars.

Recent data from space missions reveal that there are ongoing climatic changes and erosive processes that continuously modify surface features of Mars. We have investigated the seasonal dynamics of a number of morphological features located at Inca City, a representative area at high southern latitude that has undergone seasonal processes. By integrating visual information from the Mars Orbiter Camera on board the Mars Global Surveyor and climatic cycles from a Mars' General Circulation Model, and considering the recently reported evidence for the presence of water-ice and aqueous precipitates on Mars, we propose that a number of the erosive features identified in Inca City, among them spiders, result from the seasonal melting of aqueous salty solutions.

Climate↗

PubMed1994

Estimation of linear detection mechanisms for stimuli of medium spatial frequency.

Detection thresholds were obtained for a circularly-symmetric Gabor profile and Craik-Cornsweet profiles presented on a large white adapting field. These stimuli possessed peak spatial power between 1 and 6 c/deg. Their contrast was represented in an L, M and S cone contrast space. Detection thresholds were obtained for many vectors close to specific but theoretically important planes within this space. These data were fitted with a model comprising independent mechanisms, each a weighted sum of cone contrasts. The fit revealed a chromatic mechanism driven by delta L/L-delta M/M with no S cone input. Within cone contrast space, this mechanism was more sensitive than both a luminance mechanism with little S cone input but considerable variation in relative L to M cone input, and a blue-yellow chromatic mechanism.

Color Perception↗

PubMed1999

Maps of central visual space in ferret V1 and V2 lack matching inputs from the two eyes.

In the visual cortex, the representation of central visual space is supplied by matching geniculate inputs that are driven exclusively by one eye or the other. In layer 4 of early visual areas (V1 in primates and V1 and V2 in cat), these inputs form a nearly uniform array of small ocular dominance domains, while preserving overall topographic order within the cortical map. In ferret, however, ocular dominance domains in different regions of the visual cortex are strikingly irregular in size and shape. The exceptionally large size of domains in some regions implies a departure from the usual visuotopic matching of inputs from the two eyes. Using optical-imaging, electrophysiological, and anatomical techniques, we show that this regional variation is attributable to exclusively monocular maps of the central portions of the ipsilateral visual field in V1 and the contralateral visual field in V2. In addition, we document a complex interdigitation of V1 and V2 that entails a discontinuity in the mapping of visual space and fragmentation of V2 into isolated cortical territories. We suggest that both the monocularity of these cortical maps and the visuotopic discontinuity along the V1-V2 border derive from asymmetries in the crossed and uncrossed retinal pathways.

Animals↗

PubMed1995

The choice of inhalers in adults and children over six.

Available delivery systems for ambulatory use include the conventional suspension pressurized metered dose inhaler (MDI), the conventional MDI with add-on devices such as spacing chambers and several powder delivery systems. Gas-driven or ultrasonic nebulizers are also available but are generally reserved for in-hospital use or for the treatment of the most severely obstructed patients. It is difficult to select one best system for use in older children, adolescents and adults; all available systems have their deficiencies and these are outlined here. The most widely prescribed device, the MDI, is misused by some patients with claims of up to one-third of clinic patients showing inadequate inhaler technique. In the 1990s, the MDI has also been criticized for liberating chlorofluorocarbons (CFCs). On occasion, the adjuvants are said to precipitate cough. In some countries, the production of generic or second entry inhalers has been accompanied by vexing concerns over the bioequivalence of therapeutic aerosols. The problem of patient coordination with the inhaler is meant to be dealt with by a variety of add-on devices. Spacing chambers and reservoir systems improve drug delivery and treatment efficacy for some patients. Unfortunately, there are relatively few data on patient spacer technique or optimal teaching methods. There is considerable potential for patient misuse of these superficially simple devices. One common problem is that the devices become dirty and worn but are seldom replaced by patients. A more subtle problem is electrostatic drug adherence to the spacing chamber thereby reducing drug delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

PubMed1982

Auditory and visual maps of space in the optic tectum of the owl.

The receptive field properties and functional organization of visual and auditory responses were studied in the optic tectum of the barn owl (Tyto alba). Most units throughout the depth of the tectum responded to both visual and auditory stimuli. The entire visual field of each eye was represented topographically in the contralateral tectum. In the portion of the tectal map representing the zone of binocular vision, 50% of the superficial layer units and 100% of the deep; layer units were driven binocularly. The representation of the frontal binocular region of space was greatly expanded in the map; the average magnification factor was 3 times greater for the frontal binocular zone than for the monocular zone. The responses of the superficial and deep tectal units to auditory stimuli were space specific; they responded only when a sound source was located in a particular region of space, or receptive field, regardless of the intensity or type of sound used. Most auditory receptive fields contained a distinct "best area" where a sound source was most effective in driving the unit. Auditory space, as defined by receptive fields and best areas, was represented topographically in the tectum. The auditory and visual maps of space had the same orientations, positions, magnification factors, and termination coordinates at the anterior and dorsal edges of the tectum. Yet the maps lost their registry near the posterior and ventral margins where the most peripheral regions of space were represented. These characteristics suggest that the spatiotopic organization in the tectum is a compromise between a tendency for the space representations of different modalities to align and for the representation of each modality to fill the entire tectum.

Acoustic Stimulation↗

PubMed2006

Numerical simulations of type-III solar radio bursts.

The first numerical simulations are presented for type-III solar radio bursts in the inhomogeneous solar corona and interplanetary space, that include microscale quasilinear and nonlinear processes, intermediate-scale driven ambient density fluctuations, and large scale evolution of electron beams, Langmuir and ion sound waves, and fundamental and harmonic electromagnetic emission. Bidirectional coronal emission is asymmetric between the upward and downward directions, and harmonic emission dominates fundamental emission. In interplanetary space, fundamental and/or harmonic emission can be important. Langmuir and ion sound waves are bursty and the statistics of Langmuir wave energy agree well with the predictions of stochastic growth theory.

Journal Article↗