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PubMed1979

The Ninth Sir Hans Krebs Lecture. Compartmentation and communication in living systems. Ligand conduction: a general catalytic principle in chemical, osmotic and chemiosmotic reaction systems.

Chemical reactions, like osmotic reactions, are transport processes when looked at in detail. Chemical catalysis by enzymes or catalytic carriers, and osmotic catalysis by porters, may be conceived as occurring by specific ligand-conduction mechanisms. In chemiosmotic reaction systems, the pathways of specific ligand conduction are spatially orientated through anisotropic enzyme and catalytic carrier complexes in which the reactions of chemical group transfer occur as vectorial diffusion processes of group translocation down gradients of group potential that represent real spatially-directed fields of chemical force. Thus, it is easier to explain biochemistry in terms of transport than it is to explain transport in terms of biochemistry.

Animals↗

PubMed1995

Comparison of rotation models for describing DNA conformations: application to static and polymorphic forms.

A new method, based on a space-fixed rotation axis, or local helix axis, is proposed for the calculation of the relative orientation variables for a sequence of base pairs. With this method, orientation variables are determined through the rotation of a base pair about this axis. These variables uniquely determine a set of helical variables, similar to the roll, tilt, and twist, commonly used for a description of spatial orientations of internally rigid base pairs. The proposed identification of roll and tilt with the direction cosines of the space-fixed rotation axis agrees well with their customary definitions as the openings of the angles between adjoining base pairs toward the minor groove and toward the ascending (5' to 3') backbone strand, respectively. These new variables permit a more direct physical comprehension of DNA conformations and also the behavior of self-complementary sequences. These direction cosines, together with the rotation angle about the space-fixed axis, form a set of three independent orientation variables of the bases that afford some advantages over the variously defined twist, roll, and tilt angles, either for static or average forms. An example for the static form of these variables is shown through their use to interpret crystal coordinates. An example for the average of orientation variables is based on statistical calculations. In this example, the orientation variables, together with the translational variables that describe the relative displacements of a pair of adjacent base pairs, form a canonically distributed ensemble in phase space spanned by these variables. Two sets of conformational variables are generated by using two different methods for performing rotation operations on the sequences of base pairs. The first method is based on the new single rotation about a space-fixed axis of rotation. This space-fixed axis of rotation is, in fact, the local helical axis as constructed previously by others. The second method is based on three consecutive rotations by Euler angles. Because of large flexibilities and anisotropies along various conformational variables of DNA base pairs, the two sets of generated conformational variables, based on these two different methods of performing rotation operations, lead to slightly different sets of structurally different, but energetically equivalent, spatial arrangements of the base pairs.

Base Composition↗

PubMed2001

Hydrogenases in the "active" state: determination of g-matrix axes and electron spin distribution at the active site by 1H ENDOR spectroscopy.

Hydrons and electrons are substrates for the enzyme hydrogenase, but cannot be observed in X-ray crystal structures. High-resolution 1H electron nuclear double resonance (ENDOR) spectroscopy offers a means to detect the distribution of protons and unpaired electrons. ENDOR spectra were recorded from frozen solutions of the nickel-iron hydrogenases of Desulfovibrio gigas and Desulfomicrobium baculatum, in the "active" state ("Ni-C" EPR signal) and analyzed by orientationally selective simulation methods. The experimental spectra were fitted using a structural model of the nickel-iron centre based on crystallographic results, allowing for differences in electron spin distribution as well as the spatial orientation of the g-matrix ( g-tensor), and anisotropic and isotropic hyperfine couplings of the protons nearest to the nickel ion. ENDOR signals, detected after complete deuterium exchange, were assigned to six protons of the cysteines bound to nickel. The assignment took advantage of the substitution of a selenium for a sulfur ligand, which occurs naturally between the [NiFeSe] and [NiFe] hydrogenases from Dm. baculatum and D. gigas, respectively, and was found to affect just two signals. The four signals with the largest hyperfine couplings, including isotropic contributions from 4.5 to 13.5 MHz, were assigned to the beta-methylene protons of the two terminal cysteine ligands, one of which is substituted by seleno-cysteine in [NiFeSe] hydrogenase. The electron spin is delocalized onto the nickel (50%) and its sulfur ligands, with a higher proportion on the terminal than the bridging ligands. The g-matrix was found to align with the active site in such a way that the g1- g2 plane is nearly coplanar (18.3 degrees) with the plane defined by nickel and three sulfur atoms, and the g2 axis deviates by 22.9 degrees from the vector between nickel and iron. Significantly for the reaction of the enzyme, direct evidence for the binding of hydrons at the active site was obtained by the detection of H/D-exchangeable ENDOR signals.

Binding Sites↗

PubMedDate not supplied

Foundations of vectorial metabolism and osmochemistry.

Chemical transformations, like osmotic translocations, are transport processes when looked at in detail. In chemiosmotic systems, the pathways of specific ligand conduction are spatially orientated through osmoenzymes and porters in which the actions of chemical group, electron and solute transfer occur as vectorial (or higher tensorial order) diffusion processes down gradients of total potential energy that represent real spatially directed fields of force. Thus, it has been possible to describe classical bag-of-enzymes biochemistry as well as membrane biochemistry in terms of transport. But it would not have been possible to explain biological transport in terms of classical transformational biochemistry or chemistry. The recognition of this conceptual asymmetry in favour of transport has seemed to be upsetting to some biochemists and chemists; and they have resisted the shift towards thinking primarily in terms of the vectorial forces and co-linear displacements of ligands in place of their much less informative scalar products that correspond to the conventional scalar energies. Nevertheless, considerable progress has been made in establishing vectorial metabolism and osmochemistry as acceptable biochemical disciplines embracing transport and metabolism, and bioenergetics has been fundamentally transformed as a result.

Biochemistry↗

PubMed1995

Delineation of site, relative size and dynamic geometry of atrial septal defects by real-time three-dimensional echocardiography.

OBJECTIVES: This study attempted to determine the site, relative size and dynamic geometry of atrial septal defects using dynamic three-dimensional echocardiography. BACKGROUND: Recent studies have demonstrated the feasibility of dynamic three-dimensional echocardiography. Images are acquired from computerized reconstruction of sequential, tomographic ultrasound "slices" of the heart. Ultrasound images can be obtained by linear progression of a transducer within a transesophageal imaging probe. In small infants and children the large transducer size has not allowed transesophageal placement, and the probe has been placed on the thorax or in the subcostal position. Other scanning devices, housed in plastic containers, acquire images in a rotational format and can also be placed in a transthoracic or subcostal position. METHODS: Specially designed transesophageal probes and a dedicated computer unit were used for two-dimensional image retrieval and reconstruction of three-dimensional images. Sixteen patients with atrial septal defects were studied (median age 18 months, range 1 day to 18 years). In one patient, images were obtained by transesophageal probe placement; in the other 15 patients, the probe was placed in the transthoracic or subcostal position. RESULTS: A dynamic three-dimensional echocardiogram of the atrial septal defect could be obtained in 13 of the 16 patients. The distinguishing features of the atrial septal defects and their spatial orientation could be visualized in unique three-dimensional views. CONCLUSIONS: Dynamic three-dimensional imaging could be applied to the specific evaluation of atrial septal defects. Unique views of the heart allowed for spatial comprehension of the defects, rendering potentially important clinical information.

Echocardiography, Transesophageal↗

PubMed2005

Hierarchical organisation of neuro-anatomical constraints in interlimb coordination.

Based on the observation that bimanual finger tapping movements tend toward mirror symmetry with respect to the body midline, despite the synchronous activation of non-homologous muscles, F. Mechsner, D. Kerzel, G. Knoblich, and W. Prinz (2001) [Perceptual basis of bimanual coordination. Nature, 414, 69-73] suggested that the basis of rhythmic coordination is purely spatial/perceptual in nature, and independent of the neuro-anatomical constraints of the motor system. To investigate this issue further, we employed a four finger tapping task similar to that used by F. Mechsner and G. Knoblich (2004) [Do muscle matter in bimanual coordination? Journal of Experimental Psychology: Human Perception and Performance, 30, 490-503] in which six male participants were required to alternately tap combinations of adjacent pairs of index (I), middle (M) and ring (R) fingers of each hand in time with an auditory metronome. The metronome pace increased continuously from 1 Hz to 3 Hz over the course of a 30-s trial. Each participant performed three blocks of trials in which finger combination for each hand (IM or MR) and mode of coordination (mirror or parallel) were presented in random order. Within each block, the right hand was placed in one of three orientations; prone, neutral and supine. The order of blocks was counterbalanced across the six participants. The left hand maintained a prone position throughout the experiment. On the basis of discrete relative phase analyses between synchronised taps, the time at which the initial mode of coordination was lost was determined for each trial. When the right hand was prone, transitions occurred only from parallel symmetry to mirror symmetry, regardless of finger combination. In contrast, when the right hand was supine, transitions occurred only from mirror symmetry to parallel but no transitions were observed in the opposite direction. In the right hand neutral condition, mirror and parallel symmetry are insufficient to describe the modes of coordination since the hands are oriented orthogonally. When defined anatomically, however, the results in each of the three right hand orientations are consistent. That is, synchronisation of finger tapping is determined by a hierarchy of control of individual fingers based on their intrinsic neuro-mechanical properties rather than on the basis of their spatial orientation.

Adult↗

PubMed1981

Kluver-Bucy syndrome in Pick disease: clinical and pathologic correlations.

The clinical and neuropathologic findings of five cases of Pick disease were studied. All had severe anterior temporal atrophy and abnormal neurons with highly argyrophilic cytoplasm of Pick bodies. The amygdala was abnormal in every case and had severe involvement of all nuclear subdivisions. Behaviorally, the patients exhibited elements of Kluver-Bucy syndrome early in the disease. Language abnormalities were also prominent. Memory and spatial orientation were frequently spared until late. Computed tomography (CT) demonstrated marked lobar atrophy in one of two patients examined. The early appearance of Kluver-Bucy syndrome and the late occurrence of amnesia and spatial disorientation allow clinical identification of this variant of Pick disease.

Aged↗

PubMed1991

Foundations of vectorial metabolism and osmochemistry.

Chemical transformations, like osmotic translocations, are transport processes when looked at in detail. In chemiosmotic systems, the pathways of specific ligand conduction are spatially orientated through osmoenzymes and porters in which the actions of chemical group, electron and solute transfer occur as vectorial (or higher tensorial order) diffusion processes down gradients of total potential energy that represent real spatially-directed fields of force. Thus, it has been possible to describe classical bag-of-enzymes biochemistry as well as membrane biochemistry in terms of transport. But it would not have been possible to explain biological transport in terms of classical transformational biochemistry or chemistry. The recognition of this conceptual asymmetry in favour of transport has seemed to be upsetting to some biochemists and chemists; and they have resisted the shift towards thinking primarily in terms of the vectorial forces and co-linear displacements of ligands in place of their much less informative scalar products that correspond to the conventional scalar energies. Nevertheless, considerable progress has been made in establishing vectorial metabolism and osmochemistry as acceptable biochemical disciplines embracing transport and metabolism, and bioenergetics has been fundamentally transformed as a result.

Biological Transport, Active↗

PubMed2005

Characterization of steric and electronic properties of NiN2S2 complexes as S-donor metallodithiolate ligands.

The physical properties and structures of a series of six complexes of the type (NiN(2)S(2))W(CO)(4) have been used to establish electronic and steric parameters for square planar NiN(2)S(2) complexes as bidentate, S-donor ligands. According to the nu(CO) stretching frequencies and associated computed Cotton-Kraihanzel force constants of the tungsten carbonyl adducts, there is little difference in donor abilities of the five neutral NiN(2)S(2) metallodithiolate ligands in the series. The dianionic Ni(ema)(2)(-) (ema = N,N'-ethylenebis(2-mercaptoacetamide)) complex transfers more electron density onto the W(CO)(4) moiety. A ranking of donor abilities and a comparison with classical bidentate ligands is as follows: Ni(ema)(=) > {[NiN(2)S(2)](0)} > bipy approximately phen > Ph(2)PCH(2)CH(2)PPh(2) > Ph(2)PCH(2)PPh(2). Electrochemical data from cyclic voltammetry find that the reduction event in the (NiN(2)S(2))W(CO)(4) derivatives is shifted to more positive potentials by ca. 0.5 V compared to the ca. -2 V Ni(II/I) redox event in the free NiN(2)S(2) ligand, consistent with the electron drain from the nickel-dithiolate ligands by the W(CO)(4) acceptor. Differences in Ni(II/I) DeltaE(1/2) values appear to have a ligand dependence which is related to a structural feature of the hinge angle imposed by the (mu-SR)(2) bridges. Thus the angle formed by the intersection of NiN(2)S(2)/WS(2)C(2) planes has been established by X-ray diffraction analyses as a unique orientational feature of the nickel-dithiolate ligands in contrast to classical diphosphine or diimine ligands and ranges in value from 136 to 107 degrees . Variable-temperature (13)C NMR studies show that the spatial orientations of the ligands remained fixed with respect to the W(CO)(4) moiety to temperatures of 100 degrees C.

Binding Sites↗

PubMed2002

Cognitive functions after transient topographical amnesia.

Twelve consecutive patients having previously experienced one or more episodes of isolated transient topographical amnesia (TTA) underwent neuropsychological examination 6-12 months after the last episode to detect signs of global cognitive decline and to assess, in particular, cognitive functions deemed critical for topographical orientation. The test scores were compared with those of 12 normal subjects matched for age, sex, educational level and place of residence. Both patients and controls showed normal performances in all tasks. The comparison between the two groups revealed a significantly lower performance of the patient group in a task of geographical orientation, namely 'Map of Italy'. We conclude that isolated episodes of TTA in the elderly per se do not represent a sign of mental deterioration, but can be associated with frailty on survey components of spatial orientation. It remains to be explained whether this feature is a pre-existing condition favouring the occurrence of the episodes of topographical amnesia or represents a sequela.

Activities of Daily Living↗

PubMed1990

Making arm movements within different parts of space: dynamic aspects in the primate motor cortex.

The activity of 176 individual cells in the arm area of motor cortex (areas 4 and 6) was studied while monkeys made arm movements of similar direction within different parts of extrapersonal space. The behavioral paradigm used was a 3-dimensional reaction-time task aimed at dissociating the direction of movement, which remained similar across the work space, from the patterns of muscular activity and the angular joint excursions necessary to perform these movements. In agreement with other studies (Georgopoulos et al., 1982; Schwartz et al., 1988), we found that, within a given part of space, the activity of 169 (96.0%) cells studied increased most for a given preferred direction and less for other directions of movement. This change was graded in an orderly fashion. We further analyzed the orientation in space of the cells' preferred directions under the differing conditions of the task. We found that, as movements with similar trajectories were made within different parts of space, the cells' preferred directions changed spatial orientation. This change was of different magnitudes for different cells, but at the level of the population, it followed closely the changes in orientation of the arm necessary to perform the movements required by the task. Movement population vectors (Georgopoulos et al., 1983, 1986, 1988) computed from cell activity proved to be good predictors of movement direction regardless of where in space the movements were performed. These results indicate that motor cortical cells can code direction of movement in a way which is dependent on the position of the arm in space. The data are discussed in relation to the existence of mechanisms which facilitate the transformation between extrinsic and intrinsic coordinates. These transformations are necessary to perform arm movements to visual targets in space.

Animals↗

PubMed2004

The mechanism [correction of mehanism] of spatial [correction of spetial] orientation in conditions of G-stress.

Six test subjects were subjected to lateral (+Gy) and longitudinal-lateral (+Gz/+Gy) accelerations in a centrifuge with a rotation radius of 6.55 m. During rotation, test subjects were instructed to indicate the position of subjective visual vertical. Results of this study demonstrated that during exposure to +Gy and +Gz/+Gy accelerations, the direction of the indicated subjective vertical approached the direction of the resultant acceleration vector when the lateral component increased. This observed effect decreases with an increase of the longitudinal component of the acceleration. It was suggested that exposure to (i.e. "pulling") high lateral acceleration (up to 2-3 Gy) in highly maneuverable aircraft can hinder spatial orientation of a pilot due to this persistent illusory spatial position as reported above. Our analysis showed that the process of spatial orientation under the conditions of G-load influence becomes more difficult and it is depending on the compromise between visual and vestibular-proprioceptive inputs. On account of this finding, it may be proposed that under conditions of G-load influence, pilots that rely primarily on visual perception may be exposed to higher risk of spatial disorientation.

Acceleration↗

PubMed2004

In search of the sky compass in the insect brain.

Like many vertebrate species, insects rely on a sun compass for spatial orientation and long- range navigation. In addition to the sun, however, insects can also use the polarization pattern of the sky as a reference for estimating navigational directions. Recent analysis of polarization vision pathways in the brain of orthopteroid insects sheds some light onto brain areas that might act as internal navigation centers. Here I review the significance, peripheral mechanisms, and central processing stages for polarization vision in insects with special reference to the locust Schistocerca gregaria. As in other insect species, polarization vision in locusts relies on specialized photoreceptor cells in a small dorsal rim area of the compound eye. Stages in the brain involved in polarized light signaling include specific areas in the lamina, medulla and lobula of the optic lobe and, in the midbrain, the anterior optic tubercle, the lateral accessory lobe, and the central complex. Integration of polarized-light signals with information on solar position appears to start in the optic lobe. In the central complex, polarization-opponent interneurons form a network of interconnected neurons. The organization of the central complex, its connections to thoracic motor centers, and its involvement in the spatial control of locomotion strongly suggest that it serves as a spatial organizer within the insect brain, including the functions of compass orientation and path integration. Time compensation in compass orientation is possibly achieved through a neural pathway from the internal circadian clock in the accessory medulla to the protocerebral bridge of the central complex.

Animals↗

PubMed1986

Computer-aided modeling in the assessment of the biomechanical determinants of diverse skeletal patterns.

Aberrant functional patterns of the masticatory musculature have been alleged as a factor influencing the morphogenesis of mandibular dysplasias. These include such expressions as the hyperdivergent skeletal open bite and its counterpart, the hypodivergent skeletal deep bite. A lack of anatomic data dealing with the actual musculoskeletal orientations of these types has resulted in speculative reports on divergent anatomy and its purported effects. In this study anatomic dissections of a hyperdivergent and a hypodivergent human cadaver illustrated that skeletally dysmorphic types possess different spatial orientations of the masticatory adductors in relation to dentofacial structures. A two-dimensional analysis of static equilibrium using computer-aided modeling demonstrated that these two types produce biomechanically distinct modes of muscle action. Temporalis activity must be 40% higher in the hyperdivergent model as compared with its counterpart to produce a biting force of 500 N (112 lb). The data suggest a rationale for the weak biting forces previously reported in long-faced persons when compared with horizontally developed subjects. The direction of condylar reaction force was also found to vary from a vertical orientation in the hyperdivergent model to oblique in the hypodivergent model. "Physis-like" behavior of the condyle, which can orient axially toward loading forces, may present an explanation for the reported differences in the direction of condylar growth in dysmorphic persons. A finite element analysis pictured distinct regions of deformation and compression in a novel perspective to help evaluate the currency of accepted hypotheses of stress-induced osteogenesis. The data support previous work reporting a latent geometric interdependency existing between muscle orientation and mandibular morphology.

Adult↗

PubMed2006

Repeated acute exposures to hypergravity during early development subtly affect CD-1 mouse neurobehavioural profile.

Exposure to altered gravitational environment, especially during critical ontogenetic phases, may induce persistent nervous system modifications and behavioural anomalies. This study evaluated the effects of hypergravity exposure on the development of the nervous system and assessed the relevance of parity in the mother's responses to altered gravitational stimuli. CD-1 mouse pups of both sexes delivered by primiparous and biparous dams were exposed to 1h of 2 G rotationally induced hypergravity from PND2 to PND9. Sensorimotor responses and somatic growth were daily measured (PND2-PND15), ultrasonic vocalisations recorded on PNDs 2, 5 and 9, and homing behaviour evaluated on PND12. In addition, spatial orientation ability was assessed in a T-maze on PND18, while mice exploratory behaviour and locomotor activity were evaluated in an open-field test (PND21). Long-term effects of hypergravity exposure on both spatial learning (Morris water-maze test) and brain levels of NGF and BDNF were also investigated at adulthood. Rotation per se induced a delay in somatic growth, sensorimotor responses and ultrasonic vocalisation profile, while hypergravity highlighted sex differences in open-field behaviour. Strategies to solve a spatial learning task, rather than learning per se, were affected by early exposure to rotation, while hypergravity selectively altered behavioural profile in the reversal phase of the test. Early exposure to rotation per se also decreased hypothalamic BDNF levels, while hypergravity reduced NGF levels in the frontal cortex. Previous maternal experience did not interact with hypergravity exposure, while differences between offspring of primiparous and biparous dams were observed in sensorimotor development and exploratory behaviour.

Animals↗

PubMed1993

The Wellcome Prize Lecture. A map of auditory space in the mammalian brain: neural computation and development.

The experiments described in this review have demonstrated that the SC contains a two-dimensional map of auditory space, which is synthesized within the brain using a combination of monaural and binaural localization cues. There is also an adaptive fusion of auditory and visual space in this midbrain nucleus, providing for a common access to the motor pathways that control orientation behaviour. This necessitates a highly plastic relationship between the visual and auditory systems, both during postnatal development and in adult life. Because of the independent mobility of difference sense organs, gating mechanisms are incorporated into the auditory representation to provide up-to-date information about the spatial orientation of the eyes and ears. The SC therefore provides a valuable model system for studying a number of important issues in brain function, including the neural coding of sound location, the co-ordination of spatial information between different sensory systems, and the integration of sensory signals with motor outputs.

Animals↗

PubMed1979

Parabolic flight: loss of sense of orientation.

On the earth, or in level flight, a blindfolded subject being rotated at constant velocity about his recumbent long body axis experiences illusory orbital motion of his body in the opposite direction. By contrast, during comparable rotation in the free-fall phase of parabolic flight, no body motion is perceived and all sense of external orientation may be lost; when touch and pressure stimulation is applied to the body surface, a sense of orientation is reestablished immediately. The increased gravitoinertial force period of a parabola produces an exaggeration of the orbital motion experienced in level flight. These observations reveal an important influence of touch, pressure, and kinesthetic information on spatial orientation and provide a basis for understanding many of the postural illusions reported by astronauts in space flight.

Acceleration↗

PubMed1983

Freeze-fracture analysis of membrane events during early neogenesis of cilia in Tetrahymena: changes in fairy-ring morphology and membrane topography.

A freeze-fracture analysis of early neogenesis of somatic and oral cilia of Tetrahymena was conducted using exponentially grown cultures and also cells induced to undergo oral reorganization. In this report, presumptive ciliary domains (PCDs), sites of future outgrowth of somatic cilia, are identified and their membrane structure is described in detail. The fairy ring, an array of membrane particles that occurs within the PCD and appears to be a precursor of the ciliary necklace, is described. A sequence of early stages in the formation of the ciliary necklace of somatic cilia is deduced from topographical information and membrane particle arrangements and numbers. Evidence is presented that basal bodies are seated at the cell surface prior to initiation of necklace assembly and a possible role for the basal body in necklace assembly is suggested. In dividing cells, new oral cilia grow out prior to orientation of cilia-parasomal sac complexes relative to cell axes. In dividing cells and during oral reorganization, new cilia also develop prior to their alignment into membranelles. Thus, growth of cilia is independent of their spatial orientation. Fairy rings were not observed during oral reorganization. During cell division, proliferation of new cilia is accompanied by the formation of a network of junctions between a cortical system of membranous cisternae, the cortical 'alveoli'. These interalveolar junctions may serve as tracks for early positioning and orientation of new oral basal bodies.

Animals↗