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PubMed1998

Large receptive fields for optic flow detection in humans.

We used a psychophysical summation technique to study the properties of detectors tuned to radial, circular and translational motion, and to determine the spatial extent of their receptive fields. Signal-to-noise motion thresholds were measured for patterns curtailed spatially in various ways. Sensitivity for radial, circular and translational motion increased with stimulus area at a rate predicted by an ideal integrator. When sectors of noise were added to the stimulus, sensitivity decreased at a rate consistent with an ideal integrator. Summation was tested for large annular stimuli, and shown to hold up to 70 degrees in some cases, suggesting very large receptive fields for this type of motion (consistent with the physiology of neurones in the dorsal region of the medial superior temporal area (MSTd)). This is a far greater area than observed for summation of contrast sensitivity to gratings (Anderson SJ and Burr DC, Vis Res 1987;29:621-635, and to this type of stimuli (Morrone MC, Burr DC and Vaina LM, Nature 1995;376:507-509, consistent with the suggestion that the two techniques examine different levels of motion analysis.

Humans↗

PubMedDate not supplied

Invasive and non-invasive physiological monitoring of blunt trauma patients in the early period after emergency admission.

Pulmonary artery catheterization is usually not available to critically injured patients before admission to the intensive care unit, where action to correct values derived from such monitoring may be too late. Methods allowing hemodynamic monitoring during the early stages after trauma need to be explored. We used non-invasive monitoring systems (bioimpedance cardiac output monitoring, pulse oximetry and transcutaneous oximetry) to evaluate early temporal hemodynamic patterns after blunt trauma, and compared these to invasive PA monitoring. We included prospectively 134 patients monitored shortly after admission to the emergency department. The non-invasive impedance cardiac output estimations under extenuating emergency conditions approximated those of the thermodilution method: r = 0.83, r2 = 0.69, P<0.001; bias and precision were -0.02+/-0.78 l/min/m2. In the intensive care unit, these values improved further to: r = 0.91, r2 = 0.83, P<0.001; bias and precision = 0.36+/-0.59 l/min/m2. Monitoring revealed episodes of hypotension, low cardiac index, arterial hemoglobin desaturation, low transcutaneous oxygen and high transcutaneous carbon dioxide tensions, and low oxygen consumption during initial resuscitation. Low flow and poor tissue perfusion were more pronounced in non-survivors by both methods. Multicomponent non-invasive monitoring systems give continuous on-line, real-time displays of physiological data that allow early recognition of circulatory dysfunction. Such systems provide information similar to that provided by the invasive thermodilution method, and are easier and safer to use.

Adult↗

PubMed1992

[Change in the event-related skin conductivity: an indicator of the immediate importance of elaborate information processing?].

In recent psychophysiological conceptualizations of the orienting response (OR) within the framework of information processing, the OR is increasingly considered a "call for processing resources", something which is especially inferred from variations in the event-related skin conductance response (SCR). The present study, therefore, was concerned with certain implications arising from this framework or perspective, particularly in regard to the question of whether stimuli eliciting skin conductance responses obligatorily receive/evoke processing priority or not. In order to examine whether these electrodermal responses denote a capturing of attention or merely a call for processing resources, short (1 s) pure sine tones of 65 dB with sudden onset (commonly used as orienting stimuli) were inserted in a reaction time paradigm with an additional memory load. This demand was primarily given because memory processes play a key role in theories of orienting and habituation. The task was run under two different conditions of complexity, factorially combined with a novelty variation of the added auditory stimuli. The results revealed a substantial deterioration of task performance subsequent to the occurrence of the tones, which, however, was dependent on task complexity and on novelty of the tones. The task impairment is particularly remarkable as subjects were asked to avoid distractions by paying attention to the task and as the tones were introduced as subsidiary and task-irrelevant. Together with the missing effects of task complexity on phasic and tonic electrodermal activity, results suggest that information-processing conceptualizations of the OR can only be a meaningful heuristic contribution to theoretical developments about human orienting and its habituation if the setting of processing priority, its conditions, as well as its implications are adequately taken into account. In addition, it seems to be promising to consider the strength of the SCR as an index of urgency of elaborate, attention-demanding processing and not as a peripheral physiological manifestation of the OR, or, respectively, of a call for unspecific processing resources. Such a view would also do justice to the aspect of prioritization. The sufficient conditions for an OR's occurrence could, in this context, be equated with, among others, some of those which activate a mechanism subserving selective attention and, as a possible result, which lead to further and more elaborate processing of potentially important information.

Adult↗

PubMed1995

The kappa-opioid receptor is primarily postsynaptic: combined immunohistochemical localization of the receptor and endogenous opioids.

Antisera were raised against a synthetic peptide corresponding to the carboxyl terminus of the kappa-opioid receptor (KOR1). Specificity of the antisera was verified by staining of COS-7 cells transfected with KOR1 and epitope-tagged KOR1 cDNAs, by recognition by the antisera of proteins on Western blots of both transfected cells and brain tissue, by the absence of staining of both brain tissue and transfected cells after preabsorption of the antisera with the cognate peptide, and on the strong correlation between the distribution of KOR1 immunoreactivity and that of earlier ligand binding and in situ hybridization studies. Results indicate that KOR1 in neurons is targeted into both the axonal and somatodendritic compartments, but the majority of immunostaining was seen in the somatodendritic compartment. In sections from rat and guinea pig brain, prominent KOR1 staining was seen in the ventral forebrain, hypothalamus, thalamus, posterior pituitary, and midbrain. While the staining pattern was similar in both species, distinct differences were also observed. The distribution of preprodynorphin and KOR1 immunoreactivity was complementary in many brain regions, suggesting that KOR1 is poised to mediate the physiological actions of dynorphin. However, the distribution of KOR1 and enkephalin immunoreactivity was complementary in some regions as well. These results suggest that the KOR1 protein is primarily, but not exclusively, deployed to postsynaptic membranes where it mediates the effects of products of preprodynorphin and possibly preproenkephalin.

Amino Acid Sequence↗

PubMed2006

mRNA translation is compartmentalized to the endoplasmic reticulum following physiological inhibition of cap-dependent translation.

Eukaryotic cells utilize a cycle of ribosome trafficking on the endoplasmic reticulum (ER) to partition mRNAs between the cytosol and ER compartments. In this process, ribosomes engaged in the synthesis of signal sequence-bearing proteins are trafficked to the endoplasmic reticulum via the signal-recognition particle pathway and are released from the ER upon translation termination. Though the processes governing ribosome trafficking to the ER are well understood, little is known regarding the complementary ribosome release process. In this study, Coxsackie B virus (CBV) infection was used to inactivate the initiation stage of protein synthesis, thereby limiting translation to the elongation and termination stages. Ribosome partitioning between the cytosol and ER compartments was examined to determine the role of termination in ribosome release from the ER. CBV infection resulted in efficient cleavage of eIF4G and PABP, coincident with polyribosome breakdown in the cytosol and ER compartments. Termination resulted in the continued association of ribosomes with the ER compartment, rather than the expected process of ribosome release. Analyses of ribosome/mRNA loading patterns in the cytosol and ER revealed that CBV infection was accompanied by a suppression of mRNA translation in the cytosol and the sustained, although reduced, translation in the ER compartment. Direct biosynthetic labeling experiments demonstrated that protein synthesis on the ER was enhanced relative to the cytosol following CBV infection. In total, these data demonstrate that ribosome and mRNA release from the ER is regulated independent of translation termination and identify the ER as a privileged site for protein synthesis.

Blotting, Northern↗

PubMed1998

Atomic structure of progesterone complexed with its receptor.

The physiological effects of progestins are mediated by the progesterone receptor, a member of the steroid/nuclear receptor superfamily. As progesterone is required for maintenance of pregnancy, its receptor has been a target for pharmaceuticals. Here we report the 1.8 A crystal structure of a progesterone-bound ligand-binding domain of the human progesterone receptor. The nature of this structure explains the receptor's selective affinity for progestins and establishes a common mode of recognition of 3-oxy steroids by the cognate receptors. Although the overall fold of the progesterone receptor is similar to that found in related receptors, the progesterone receptor has a quite different mode of dimerization. A hormone-induced stabilization of the carboxy-terminal secondary structure of the ligand-binding domain of the progesterone receptor accounts for the stereochemistry of this distinctive dimer, explains the receptor's characteristic pattern of ligand-dependent protease resistance and its loss of repression, and indicates how the anti-progestin RU486 might work in birth control. The structure also indicates that the analogous 3-keto-steroid receptors may have a similar mechanism of action.

Amino Acid Sequence↗

PubMed1992

Song presentation induces gene expression in the songbird forebrain.

We investigated the participation of genomic regulatory events in the response of the songbird brain to a natural auditory stimulus of known physiological and behavioral relevance, birdsong. Using in situ hybridization, we detected a rapid increase in forebrain mRNA levels of an immediate-early gene encoding a transcriptional regulator (ZENK; also known as zif-268, egr-1, NGFI-A, or Krox-24) following presentation of tape-recorded songs to canaries (Serinus canaria) and zebra finches (Taeniopygia guttata). ZENK induction is most marked in a forebrain region believed to participate in auditory processing and is greatest when birds hear the song of their own species. A significantly lower level of induction occurs when birds hear the song of a different species and no induction is seen after exposure to tone bursts. Cellular analysis indicates that the level of induction reflects the proportion of neurons recruited to express the gene. These results suggest a role for genomic responses in neural processes linked to song pattern recognition, discrimination, or the formation of auditory associations.

Acoustic Stimulation↗

PubMed2005

Physiological system identification with the Kalman filter in diffuse optical tomography.

Diffuse optical tomography (DOT) is a noninvasive imaging technology that is sensitive to local concentration changes in oxy- and deoxyhemoglobin. When applied to functional neuroimaging, DOT measures hemodynamics in the scalp and brain that reflect competing metabolic demands and cardiovascular dynamics. Separating the effects of systemic cardiovascular regulation from the local dynamics is vitally important in DOT analysis. In this paper, we use auxiliary physiological measurements such as blood pressure and heart rate within a Kalman filter framework to model physiological components in DOT. We validate the method on data from a human subject with simulated local hemodynamic responses added to the baseline physiology. The proposed method significantly improved estimates of the local hemodynamics in this test case. Cardiovascular dynamics also affect the blood oxygen dependent (BOLD) signal in functional magnetic resonance imaging (fMRI). This Kalman filter framework for DOT may be adapted for BOLD fMRI analysis and multimodal studies.

Algorithms↗

PubMed2004

Geometric trajectory analysis of metabolic responses to toxicity can define treatment specific profiles.

Metabonomics can be viewed as the process of defining multivariate metabolic trajectories that describe the systemic response of organisms to physiological perturbations through time. We have explored the hypothesis that the homothetic geometry of a metabolic trajectory, i.e., the metabolic response irrespective of baseline values and overall magnitude, defines the mode of response of the organism to treatment and is hence the key property when considering the similarity between two sets of measurements. A modeling strategy to test for homothetic geometry, called scaled-to-maximum, aligned, and reduced trajectories (SMART) analysis, is presented that together with principal components analysis (PCA) facilitates the visualization of multivariate response similarity and hence the interpretation of metabonomic data. Several examples of the utility of this approach from toxicological studies are presented as follows: interlaboratory variation in hydrazine response, CCl(4) dose-response relationships, and interspecies comparison of bromobenzene toxicity. In each case, the homothetic trajectories hypothesis is shown to be an important concept for the successful multivariate modeling and interpretation of systemic metabolic change. Overall, geometric trajectory analysis based on a homothetic modeling strategy like SMART facilitates the amalgamation and comparison of metabonomic data sets and can improve the accuracy and precision of classification models based on metabolic profile data. Because interlaboratory variation, normal physiological variation, dose-response relationships, and interspecies differences are also key areas of concern in genomic and proteomic as well as metabonomic studies, the methods presented here may also have an impact on many other multilaboratory efforts to produce screenable "-omics" databases useful for gauging toxicity in safety assessment and drug discovery.

Animals↗

PubMed2003

Symbiotic status, phosphate, and sucrose regulate the expression of two plasma membrane H+-ATPase genes from the mycorrhizal fungus Glomus mosseae.

The establishment of the arbuscular mycorrhizal symbiosis results in a modification of the gene expression pattern in both plant and fungus to accomplish the morphological and physiological changes necessary for the bidirectional transfer of nutrients between symbionts. H(+)-ATPase enzymes play a key role establishing the electrochemical gradient required for the transfer of nutrients across the plasma membrane in both fungi and plants. Molecular analysis of the genetic changes in arbuscular mycorrhizal fungi during symbiosis allowed us to isolate a fungal cDNA clone encoding a H(+)-ATPase, GmPMA1, from Glomus mosseae (BEG12). Despite the high conservation of the catalytic domain from H(+)-ATPases, detailed analyses showed that GmPMA1 was strongly related only to a previously identified G. mosseae ATPase gene, GmHA5, and not to the other four ATPase genes known from this fungus. A developmentally regulated expression pattern could be shown for both genes, GmPMA1 and GmHA5. GmPMA1 was highly expressed during asymbiotic development, and its expression did not change when entering into symbiosis, whereas the GmHA5 transcript was induced upon plant recognition at the appressorium stage. Both genes maintained high levels of expression during intraradical development, but their expression was reduced in the extraradical mycelium. Phosphate, a key nutrient to the symbiosis, also induced the expression of GmHA5 during asymbiotic growth, whereas sucrose had a negative effect. Our results indicate that different fungal H(+)-ATPases isoforms might be recruited at different developmental stages possibly responding to the different requirements of the life in symbiosis.

Amino Acid Sequence↗

PubMed2006

Analysis of complex physiological systems by information flow: a time scale-specific complexity assessment.

In the last two decades conventional linear methods for biosignal analysis have been substantially extended by non-stationary, non-linear, and complexity approaches. So far, complexity is usually assessed with regard to one single time scale, disregarding complex physiology organised on different time scales. This shortcoming was overcome and medically evaluated by information flow functions developed in our research group in collaboration with several theoretical, experimental, and clinical partners. In the present work, the information flow is introduced and typical information flow characteristics are demonstrated. The prognostic value of autonomic information flow (AIF), which reflects communication in the cardiovascular system, was shown in patients with multiple organ dysfunction syndrome and in patients with heart failure. Gait information flow (GIF), which reflects communication in the motor control system during walking, was introduced to discriminate between controls and elderly patients suffering from low back pain. The applications presented for the theoretically based approach of information flow confirm its value for the identification of complex physiological systems. The medical relevance has to be confirmed by comprehensive clinical studies. These information flow measures substantially extend the established linear and complexity measures in biosignal analysis.

Adult↗

PubMed1990

Petit mal epilepsy and parkinsonian tremor: hypothesis of a common pacemaker.

Rhythmic oscillation in neuronal systems may serve physiological purposes or may interfere with normal functions of the brain. In disorders of petit mal epilepsy and parkinsonian tremor, centrally and peripherally observable rhythmic patterns are due to network oscillations of thalamocortical cells. This article reviews the afferent mechanisms that might be critically involved in controlling the ionic conductances of thalamic neurons in the behaving organism. We propose that during active behavior the subcortical aminergic and cholinergic inputs to the thalamus act as anti-burst and anti-oscillation mechanisms. We suggest further that the thalamopetal GABAergic inputs (pars reticulata of substantia nigra, entopeduncular nucleus, pallidum) are burst- and oscillation-promoting systems, whose output is controlled by the striatum. Experimental or disease-related decrease of the striatal dopamine levels is hypothesized to increase the efficacy of the GABAergic burst-promoting systems resulting in rhythmic network oscillation of thalamocortical neurons during rest. The recognition of the overlapping neuronal mechanisms in petit mal epilepsy and parkinsonian tremor, and the multistage control of thalamic oscillation suggests that drugs effectively used in petit mal attacks may be effective in levodopa-refractory parkinsonian tremor, and conversely, epileptic patients may benefit from drugs acting on the extrapyramidal system.

Epilepsy, Absence↗

PubMed2006

Transcriptional regulation of neuropeptide and peptide hormone expression by the Drosophila dimmed and cryptocephal genes.

The regulation of neuropeptide and peptide hormone gene expression is essential for the development and function of neuroendocrine cells in integrated physiological networks. In insects, a decline in circulating ecdysteroids triggers the activation of a neuroendocrine system to stimulate ecdysis, the behaviors used to shed the old cuticle at the culmination of each molt. Here we show that two evolutionarily conserved transcription factor genes, the basic helix-loop-helix (bHLH) gene dimmed (dimm) and the basic-leucine zipper (bZIP) gene cryptocephal (crc), control expression of diverse neuropeptides and peptide hormones in Drosophila. Central nervous system expression of three neuropeptide genes, Dromyosuppressin, FMRFamide-related and Leucokinin, is activated by dimm. Expression of Ecdysis triggering hormone (ETH) in the endocrine Inka cells requires crc; homozygous crc mutant larvae display markedly reduced ETH levels and corresponding defects in ecdysis. crc activates ETH expression though a 382 bp enhancer, which completely recapitulates the ETH expression pattern. The enhancer contains two evolutionarily conserved regions, and both are imperfect matches to recognition elements for activating transcription factor-4 (ATF-4), the vertebrate ortholog of the CRC protein and an important intermediate in cellular responses to endoplasmic reticulum stress. These regions also contain a putative ecdysteroid response element and a predicted binding site for the products of the E74 ecdysone response gene. These results suggest that convergence between ATF-related signaling and an important intracellular steroid response pathway may contribute to the neuroendocrine regulation of insect molting.

Animals↗

PubMed1999

Word ambiguity and the optimal viewing position in reading.

The optimal viewing position phenomenon discovered by (O'Regan, J. K., Lévy-Schoen, A., Pynte, J., Brugaillère, B. (1984). Convenient fixation location within isolated words of different length and structure. Journal of Experimental Psychology: Human Perception and performance. 10 (2), 250-257) is characterized by a minimization of gaze duration on a word and maximization of word recognition rates when the eye fixates a word near its center. Subsequent studies (Holmes, V. M., & O'Regan, J. K. (1987). Decomposing french words. In J. K. O'Regan, & A. Lévy-Schoen, Eye movements: from physiology to cognition, North-Holland, Amsterdam, 459-466; O'Regan, J. K., & Lévy-Schoen, A. (1987). Eye movement strategy and tactics in word recognition and reading. In M. Coltheart, Attention and performance XII: the psychology of reading, Erlbaum, Hillsdale N.J., 363-383) have shown that lexical structure can affect the location of the optimal viewing position. In this paper we show that the optimal viewing position is near to the position which minimizes word ambiguity arising from incomplete recognition of the letters in the word. This conclusion is supported by a statistical analysis based on inter-letter correlations in English and French word corpuses.

Fixation, Ocular↗

PubMed2000

The initial pathogenesis of cadmium induced renal toxicity.

The novel application of magic angle spinning 1H NMR spectroscopy, coupled with pattern recognition techniques, has identified biochemical changes in lipid and glutamate metabolism that precede classical nephrotoxicity. These changes occurred in the bank vole (Clethrionomys glareolus) after chronic dosing, at a low level of exposure and at a renal Cd(2+) concentration (8.4 microgram/g dry wt) that was nearly two orders of magnitude below the WHO critical organ concentration (200 microg/g wet wt). These early stage effects of Cd(2+) on the biochemistry of renal tissue may reflect adaptation mechanisms to the toxic insult or the preliminary stages of the toxicological cascade.

Acidosis, Renal Tubular↗

PubMed2004

Physiology of human photosensitivity.

Human epileptic photosensitivity has been studied in several ways. (a) Visual stimulation that resembles the stimulation normally responsible for seizures, such as that from televisions or videogames, both of which typically use cathode ray tubes in which the display is created in a flickering pattern. Such stimulation is often rendered yet more epileptogenic by programmes with content that also involves flashing or patterned material. (b) Elementary visual stimuli that enable inferences to be drawn concerning the physiological trigger mechanisms. The topographic distribution of epileptiform EEG activity in response to such stimuli has complemented this approach, leading to the inference that the trigger is cortical and requires sychronised mass action of neurons. (c) Stimuli that avoid paroxysmal EEG activity and permit an investigation of the subepileptic response to visual stimuli, using the evoked potential. This has revealed abnormalities in the cortical mechanisms that control the response to strong visual stimulation.

Epilepsy, Reflex↗

PubMed1995

Amblyopia: a tale of two approaches.

Our understanding of the physiological basis for amblyopia in humans has undergone dramatic changes over the past two decades. The first such change occurred when we were first able to record from single neurones in different parts of the visual pathway and develop neural models of the anomaly. The second came from psychophysical investigations and evaluations of these animal models. Our understanding has progressed from one focused on the properties of single cortical cells to an appreciation of the anomalous behaviour of cellular networks.

Amblyopia↗

PubMed1993

Motion transparency and coherence in plaids: the role of end-stopped cells.

Humans do not confound the motion of shadows cast upon a surface with the motion of the surface itself, although schemes that propose recombination of orientation-selective motion signals into a rigid motion percept of two-dimensional patterns would predict that they should do so. We propose a simple scheme that avoids recombination and instead attributes perception of two-dimensional pattern motion to the activation of orientation-selective end-stopped units that operate on the logarithm of the luminance. The proposed units respond to the change of contrast along a line, which typically occurs at an intersection. They are not active, however, when a shadow border intersects the edge of an object, because contrast does not change along either of these edges. Thus, end-stopped units signal the motion of transparent intersections weakly or not at all, and the independent motions of the shadow border and the object prevail. We tested two implications of this scheme, using plaids with variable intersection luminance. First, when the intersection luminance was such that it kept the contrast along the intersecting lines nearly constant, the sensitivity for the rigid plaid's direction of motion was minimal, and the sliding motion of the components prevailed. This occurred for light bars on dark backgrounds and for dark bars on light backgrounds. Thus, the effect of the intersection's luminance on the balance between the percepts of rigid-plaid motion and the motion of sliding components was independent of contrast inversion of bar and background. Secondly, when thin lines with the same luminance as the bars covered the borders of the intersection, the intersection's luminance did not affect the rigid-plaid motion percept very much, even when it corresponded to a transparent intersection. This indicates that, when the edges of the intersection and those of the bars were not collinear, the nulling of the end-stopped units did not occur. This result is in line with physiological studies, which showed that the response of an end-stopped cell to a line is only partially inhibited when a similar line is presented non-collinearly with the first in the inhibitory end-zone of its receptive field. Our results are consistent with a scheme in which a second stage of motion detectors combines signals of orientation-selective end-free and orientation-selective end-stopped units for perception of the rigid motion of two-dimensional patterns.

Humans↗