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Results for “Pattern Recognition, Physiological”

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PubMed1998

Immuno-detection of aluminium and aluminium induced conformational changes in calmodulin--implications in Alzheimer's disease.

Binding of calcium to calmodulin (CAM) induces specific structural rearrangements in the whole protein molecule. Ca2+ organizes and stabilizes the four-domains structure of calmodulin in a helical, active conformation that can bind to its target proteins; the central helix remaining flexible is an essential condition for their bio-recognition. The conformation of calmodulin, and its efficacy to interact with target proteins, is profoundly altered when bound to metal ions other than calcium. As recently reported, the local structural changes of CaM, which occur upon aluminium binding, lead to the impairment of protein flexibility and to the loss of its ability to interact with several other proteins, which may decrease or inhibit the regulatory character of calmodulin. In this study we followed conformational changes occurring in the calmodulin molecule after aluminium binding using highly specific monoclonal antibodies (mAbs) able to differentiate between the conformational states of calmodulin, as well as mAbs which recognize aluminium free or bound to proteins. Under the same experimental conditions, mAb CAM-1, a Ca2+ conformation sensitive antibody raised against calmodulin, fails to recognize the calmodulin-aluminium complex, despite the presence of Ca2+, while the anti-Al antibodies show a maximal binding pattern towards their antigen. These data suggest that Al3+ ions bind to calmodulin in the presence of Ca2+ ions, leading to an inactive, reversible conformation, instead of its physiological active form. Alteration of the conformation of calmodulin imposed by Al binding may have possible implications in the neurotoxicity mechanism related to Alzheimer's disease.

Aluminum↗

PubMed2000

Development of specific connectivity between premotor neurons and motoneurons in the brain stem and spinal cord.

Astounding progress has been made during the past decade in understanding the general principles governing the development of the nervous system. An area of prime physiological interest that is being elucidated is how the neural circuitry that governs movement is established. The concerted application of molecular biological, anatomical, and electrophysiological techniques to this problem is yielding gratifying insight into how motoneuron, interneuron, and sensory neuron identities are determined, how these different neuron types establish specific axonal projections, and how they recognize and synapse upon each other in patterns that enable the nervous system to exercise precise control over skeletal musculature. This review is an attempt to convey to the physiologist some of the exciting discoveries that have been made, within a context that is intended to link molecular mechanism to behavioral realization. The focus is restricted to the development of monosynaptic connections onto skeletal motoneurons. Principal topics include the inductive mechanisms that pattern the placement and differentiation of motoneurons, Ia sensory afferents, and premotor interneurons; the molecular guidance mechanisms that pattern the projection of premotor axons in the brain stem and spinal cord; and the precision with which initial synaptic connections onto motoneurons are established, with emphasis on the relative roles played by cellular recognition versus electrical activity. It is hoped that this review will provide a guide to understanding both the existing literature and the advances that await this rapidly developing topic.

Afferent Pathways↗

PubMed1998

Self-association of G-rich oligodeoxyribonucleotides under conditions promoting purine-motif triplex formation.

Efficient purine-motif triple-helix formation with guanosine/thymidine-rich oligodeoxyribonucleotides requires the presence of divalent cations (e.g., Mg2+) or polyamines at physiologic concentrations. However, under such conditions, we found that G-rich oligonucleotides were capable of self-association. Mixing experiments indicated a stoichiometry of two G-rich oligonucleotide strands in each complex. Dimerization was proportional to the oligonucleotide length, facilitated by increasing concentrations of multivalent cations, and inhibited by monovalent cations that promote G-quartet formation (e.g., K+, Rb+ NH4+). Although dimer formation was relatively slow (t(1/2) approximately 20 minutes), these species were quite stable, with dissociation rates on the order of days. Methylation protection experiments indicated that these dimers exhibited protected N7 position on most all guanines consistent with Hoogsteen base pairing, although this pattern differed from that observed under conditions favoring intramolecular quadruplex formation. Most important, G-rich oligonucleotide dimers were less capable of purine-motif triplex formation than were their denatured counterparts. Thus, these data indicated that G-rich oligodeoxyribonucleotides can form alternate self-associated structures under conditions that do not favor standard quadruplex formation and that these species can have altered properties with regard to their recognition of biologic targets.

Base Composition↗

PubMed1998

Xa21D encodes a receptor-like molecule with a leucine-rich repeat domain that determines race-specific recognition and is subject to adaptive evolution.

The rice Xa21 gene confers resistance to Xanthomonas oryzae pv oryzae in a race-specific manner. Analysis of the inheritance patterns and resistance spectra of transgenic plants carrying six Xa21 gene family members indicated that one member, designated Xa21D, displayed a resistance spectrum identical to that observed for Xa21 but conferred only partial resistance. Xa21D encodes a receptor-like protein carrying leucine-rich repeat (LRR) motifs in the presumed extracellular domain. The Xa21D transcript terminates shortly after the stop codon introduced by the retrotransposon Retrofit. Comparison of nucleotide substitutions in the LRR coding regions of Xa21 and Xa21D provided evidence of adaptive selection. Both functional and evolutionary evidence indicates that the Xa21D LRR domain controls race-specific pathogen recognition.

Adaptation, Physiological↗

PubMed1989

[Are the lesions responsible for prosopagnosia always bilateral?].

To localize the lesions responsible for prosopagnosia one must first consider how recent anatomico-physiological data have modified our view of the visual system: the visual cortex has been parceled into a mosaic of visual areas, each of them processing preferentially a particular feature (form, colour, movement); there is evidence of a face area in the monkey temporal lobe, and a new model of the inferior longitudinal fasciculus has been offered. It is currently accepted that face recognition deficits are due to bilateral occipito-temporal lesions, but in view of several recent reports in which the lesions were localized on CT or MRI one may doubt that these lesions are necessarily bilateral. In some cases a right unilateral lesion seemed to be sufficient to induce prosopagnosia.

Agnosia↗

PubMed2004

Bacterial colonization and the development of intestinal defences.

In humans, intestinal defences develop during gestation and, at full term, have the capacity to respond in an appropriate manner to infectious agents and foreign antigens. Before an active protective response can occur, however, the gut must first be exposed to colonizing bacteria. Colonization with diverse intestinal microbes is necessary for the development of important gut defenses such as the synthesis and secretion of polymeric immunoglobulin A and the generation of a balanced T helper (Th) cell response. Insights into normal immune physiological development of the gut have been made by studying the germ-free animal and intestinal defenses. These studies have provided insights into the physiology of immune responses. Two important immunological functions are the secretion of polymeric immunoglobulin A to protect the intestinal surface against harmful stimuli and inhibition of the systemic response to commensal bacteria and food proteins (eg, oral tolerance) to prevent chronic inflammation. Neither function exists in the germ-free state, but rapidly develops after conventionalization (colonization) of the germ-free animal. In the present review, the importance of bacterial colonization on the appearance of normal mucosal immune function and to the clinical consequences of inadequate colonization to the development of disease will be discussed. For example, excessive Th2 activity can lead to atopy, whereas Th1 predominance is found in conditions such as Helicobacter pylori gastritis and Crohn's disease. With the eradication of infectious diseases in developed countries in the past three decades, the incidence of atopic and autoimmune diseases has increased. This epidemiological observation has been explained by the 'hygiene hypothesis', which suggests that a reduction in microbial burden by public health measures has contributed to an immunological imbalance in the intestine. A family of pattern recognition receptors (Toll-like receptors) on gut lymphoid and epithelial cells mediates innate immune responses to bacterial molecular patterns and, thereby, orchestrates acquired immunity. As the role of bacterial communication within the gut (bacterial-epithelial cross-talk) is clarified, physicians should be able to modulate gut immune responses, for example, by the use of probiotics.

Antigens, Bacterial↗

PubMedDate not supplied

A molecular recognition paradigm: promiscuity associated with the ligand-receptor interactions of the activin members of the TGF-beta superfamily.

The structure-function properties of the pleiotropic activins and their relationship to other members of the transforming growth factor-beta superfamily of proteins are described. In order to highlight the molecular promiscuity of these growth factors, emphasis has been placed on molecular features associated with the recognition by activin A and the bone morphogenic proteins of the corresponding extracellular domains of the ActRI and ActRII receptors. The available evidence suggests that the homodimeric activin A in its various functional roles has the propensity to fulfill key tasks in the regulation of mammalian cell behaviour, through coordination of numerous transcriptional and translational processes. Because of these profound effects, under physiologically normal conditions, activin A levels are closely controlled by a variety of binding partners, such as follistatin-288 and follistatin-315, alpha(2)-macroglobulin and other proteins. Moreover, the subunits of other members of the activin subfamily, such as activin B or activin C, are able to form heterodimers with the activin A subunit, thus providing a further avenue to positively or negatively control the physiological concentrations of activin A that are available for interaction with specific receptors and induction of cell signaling events. Based on data from X-ray crystallographic studies and homology modeling experiments, the molecular architecture of the ternary receptor-activin ligand complexes has been dissected, permitting rationalization in structural terms of the pattern of interactions that are the hallmark of this protein family.

Activin Receptors↗

PubMed2006

The mechanism for stochastic resonance enhancement of mammalian auditory information processing.

BACKGROUND: In a mammalian auditory system, when intrinsic noise is added to a subthreshold signal, not only can the resulting noisy signal be detected, but also the information carried by the signal can be completely recovered. Such a phenomenon is called stochastic resonance (SR). Current analysis of SR commonly employs the energies of the subthreshold signal and intrinsic noise. However, it is difficult to explain SR when the energy addition of the signal and noise is not enough to lift the subthreshold signal over the threshold. Therefore, information modulation has been hypothesized to play a role in some forms of SR in sensory systems. Information modulation, however, seems an unlikely mechanism for mammalian audition, since it requires significant a priori knowledge of the characteristics of the signal. RESULTS: We propose that the analysis of SR cannot rely solely on the energies of a subthreshold signal and intrinsic noise or on information modulation. We note that a mammalian auditory system expends energy in the processing of a noisy signal. A part of the expended energy may therefore deposit into the recovered signal, lifting it over threshold. We propose a model that in a rigorous mathematical manner expresses this new theoretical viewpoint on SR in the mammalian auditory system and provide a physiological rationale for the model. CONCLUSION: Our result indicates that the mammalian auditory system may be more active than previously described in the literature. As previously recognized, when intrinsic noise is used to generate a noisy signal, the energy carried by the noise is added to the original subthreshold signal. Furthermore, our model predicts that the system itself should deposit additional energy into the recovered signal. The additional energy is used in the processing of the noisy signal to recover the original subthreshold signal.

Algorithms↗

PubMed1985

Seizure recognition and analysis.

The processing of EEGs with respect to epileptic seizures falls in two main categories: automatic recognition of seizures during long-term monitoring and analysis of seizures to extract information not available from visual inspection. Automatic seizure recognition is a complex problem because the EEG during seizures is not well defined morphologically; imperfect automatic recognition is nevertheless possible and it can simplify the task of monitoring and increase its diagnostic yield. The widespread use of monitoring techniques has made the recording of seizures relatively frequent. It has therefore become worthwhile to develop procedures for analyzing seizure patterns in detail, particularly the propagation of seizure activity between different brain structures. The computation of time differences of a few milliseconds between two channels is possible and has been shown to be meaningful. Such an analysis allows to follow the structures involved and the different stages of evolution of a seizure, the structures likely to be 'driving' seizure activity and the possible routes of propagation. These methods are reviewed and their use is illustrated.

Animals↗

PubMed2004

The combined application of FTIR microspectroscopy and ToF-SIMS imaging in the study of prostate cancer.

At present. a prognosis for prostate cancer (CaP) is determined by its accurate assessment of disease grade and stage. Histopathological typing using the Gleason grading system is the most universally accepted approach for grading CaP and provides an indication as to the aggressiveness of the tumour at the time of presentation. However, this system is based upon a visual criterion of pattern recognition that is operator dependent and subject to intra- and inter-observer variability, which can result in inappropriate patient management. Thus, there is a need for a molecular based diagnostic technique to grade tissue samples in a reliable and reproducible manner. In this paper we report a prototype diagnostic classifier for Gleason graded CaP tissue, based upon the integration of FTIR microspectroscopy with linear discriminant analysis (LDA). Blind testing of this model demonstrates 80% agreement of FTIR-LDA grade to histology, for the specimens analysed. We also study the effects of connective tissue absorption upon the area ratio of peaks at A1030 cm(-1)/A1080(cm(-1) which we use as a criterion to biospectroscopically map and distinguish areas of benign from malignant tissue. In addition, imaging time-of-flight secondary ion mass spectrometry (ToF-SIMS) has been applied to study freeze-dried, freeze-fractured prostate cancer cells in vitro. Preliminary results demonstrate localisation of various species including K, Ca and Mg within the cytoplasm that are present at millimolar concentrations and vital to cell physiology. The soft ionisation technique employed also permits for molecular information to be obtained and this has been used to evaluate chemically, different fracture planes within the analysis area.

Algorithms↗

PubMed2004

Hypoglycemia in type 1 diabetes mellitus: pathophysiology and prevention.

Spontaneous hypoglycemia is uncommon in the general (nondiabetic) population, but iatrogenic hypoglycemia is rife in patients with type 1 diabetes mellitus, among whom hypoglycemia constitutes a barrier to optimal glycemic control. The obligate dependence on exogenous insulin, together with the current imperfection in insulin therapies, generates degrees of blood glucose fluctuations that often exceed physiological boundaries in these patients. Downward swings in blood glucose levels, if sustained, result in hypoglycemia and significant morbidity and mortality. Hypoglycemia in type 1 diabetes indicates an imbalance between caloric supply and glucose use in response to insulin or exercise. Counterregulatory mechanisms that auto-correct iatrogenic hypoglycemia often become progressively impaired in these patients. This defective counterregulation, together with the imperfections in insulin delivery, set the stage for significant morbidity from iatrogenic hypoglycemia. Recurrent episodes of iatrogenic hypoglycemia induce a state of hypoglycemia unawareness and defective counterregulation, which defines the syndrome of hypoglycemia-associated autonomic failure (HAAF). The reduced awareness of, and counterregulatory responses to, hypoglycemia in patients with HAAF lead to worsening episodes of severe hypoglycemia. Approaches to the prevention of hypoglycemia include glucose monitoring, patient education, meal planning, and medication adjustment. In patients with HAAF, scrupulous avoidance of iatrogenic hypoglycemia may restore the symptomatic and counterregulatory responses to hypoglycemia. Behavioral training focusing on recognition of the more subtle symptoms and signs of evolving hypoglycemia may be beneficial to some patients with HAAF. A methodical search for the pattern and etiology of iatrogenic hypoglycemia is a prerequisite for the identification of the best preventive approach. With proper education, patients with type 1 diabetes and their physicians can learn to prevent or minimize the risk of hypoglycemia while pursuing excellence in glycemic control.

Awareness↗

PubMed2005

Interaction of sensory and cognitive processes during visual recognition: the role of the associative areas of the cerebral cortex.

The first part of the present study used a model of Alzheimer's disease in two groups of animals (three monkeys in each), given injections of neurotoxins (monkeys of group I) and physiological saline (monkeys of group II). Before injections, all monkeys were trained to discriminate stimuli containing different types of information (spatial frequency grids and geometrical figures of different colors and with different spatial relationships between objects) and to perform spatial selection. The dynamics of impairments in the characteristics of working memory were identified using delayed differentiation tasks in monkeys of both groups before injections and every two months after injections. Quantitative measures of impairments were made using the entropy of visual recognition, which characterizes uncertainty in decision-taking. The development of Alzheimer's disease in rhesus macaques was characterized by a deficit of working memory, resulting from lesions to the two component processes of memory. Impairments of the first of these in monkeys of group I were manifest as a significant increase in entropy, which is associated with correct decision-taking. The magnitude of the increase depended on the type of visual information. Impairments of the second component were characterized by increases in entropy associated with refusals to take decisions and were independent of the delay duration and the type of visual information. Monkeys given injections of physiological saline showed no significant changes in these characteristics. The features of working memory were also studied in the second part of the investigation, using four groups of Rhesus macaques: intact, those with bilateral extirpation of the sulcus principalis or field 7 or both: degradation again identified two components. Entropy associated with this was increased significantly for most of the stimuli tested on monkeys of all extirpation groups as compared with intact animals. Significant differences were found in these characteristics for a number of stimuli, which depended on the location of the structures removed. The characteristics of impairments of the components of working memory resulting in the development of Alzheimer's disease showed that the cholinergic mechanisms responsible for sensory processing differ from those involved in decision-taking. The structural-functional organization of the interaction of sensory and cognitive processes controlled by the motivation and attention systems is discussed, as is the role of the associative areas of the cortex.

Animals↗

PubMed2005

Attentional gating in primary visual cortex: a physiological basis for dyslexia.

The visual magnocellular pathway is known to play a central part in visuospatial attention and in directing attention to specific parts of the visual world in serial search. It is proposed that, in the case of reading, this mechanism is trained to perform a sequential gating of visual information coming into the primary visual cortex to enable further orderly processing by the ventral stream. This scheme, taken together with the potential for plasticity between the different afferent channels in the case of a relative impairment of the magnocellular system, can provide some limited rationale for the beneficial effects that have been claimed for the use of coloured overlays and glasses.

Attention↗

PubMed2004

Functional plasticity of macrophages: reversible adaptation to changing microenvironments.

There has been substantial research activity in the past decade directed at phenotyping macrophage lineages and defining macrophage functional subsets or patterns of activity. The emphasis over the past 2-3 years has been to divide macrophage functional patterns into type 1 (Th1-driven) or type 2 (Th2-driven) functions. However, a huge array of environmental factors (including cytokines, chemokines, pattern recognition receptors, hormones) differentially regulates macrophage response patterns, resulting in the display of numerous distinct, functional phenotypes. Upon stimulation, a macrophage does not display just a single set of functions but rather displays a progression of functional changes in response to the progressive changes in its microenvironment. The remarkable ability of monocytes and tissue macrophages to adapt to changes in their microenvironment challenges the thesis that macrophages displaying unique tissue-specific or response-specific, functional patterns represent distinct lineages. With the exception of mature osteoclasts and mature dendritic cells, evidence supporting stable differentiation as the basis for macrophage functional heterogeneity is equivocal. The concept of whether macrophages develop into functional subsets as opposed to continuously adapting their functional pattern in response to the changing environment of a progressive inflammatory response is important to resolve from the perspectives of therapeutic targeting and understanding the role of macrophages in disease pathogenesis.

Adaptation, Physiological↗

PubMed1994

Transparent motion perception as detection of unbalanced motion signals. III. Modeling.

In the preceding two companion articles we studied the conditions under which transparent motion perception occurs through psychophysical experiments, and investigated the underlining neural mechanisms through physiological recordings. The main finding of our perceptual experiments was that whenever a display has finely balanced motion signals in all local areas, it is perceptually nontransparent, and that transparent displays always contain motion signals in different directions that are either spatially unbalanced, or unbalanced in their disparity or spatial frequency contents. In the physiological experiments, we found two stages in the processing of transparent stimuli. The first stage is located primarily in area V1. At this stage motion measurements are made and V1 cells respond well to both the balanced, nontransparent stimuli and the unbalanced, perceptually transparent stimuli. The second stage is located primarily in area MT. MT cells show strong suppression between opposite directions of motion. The suppression for the unbalanced, transparent stimuli is significantly less than that for the balanced, nontransparent stimuli. Therefore, the activity in the second, MT stage correlates better with the perception of motion transparency than the first, V1 stage, which does not distinguish reliably between transparent and nontransparent motion. The above experiments suggest a two-stage model of motion perception with a motion measurement stage in V1 and an opponent-direction suppression stage in area MT. In this article we explicitly test this model through analysis and computer simulations, and compare the response of the model to the perceptual and physiological results using the same balanced and unbalanced stimuli we used in the experiments. In the first stage of the computational model, motion energies in different spatial frequency and disparity ranges are extracted from each local region. Similar to V1, this stage does not distinguish between the balanced and unbalanced stimuli. In the subsequent stage motion energies of opposite directions but with same spatial frequency and disparity contents suppress each other using subtractive or divisive inhibition. This stage responds significantly better to the transparent stimuli than to the nontransparent ones, in agreement with MT activity.

Animals↗

PubMed2006

Association of different prediction methods for determination of the efficiency and selectivity on neuron-based sensors.

A technique has been developed to determine the efficiency and the selectivity of a single neuron-based sensor in identifying the nature of the chemical agents in an unknown sample. This has been achieved by exploiting the unique electrical identifiers, also known as "signature patterns", generated by the neuronal cell membrane. These were generated based on the variations to the extracellular electrical activity, due to the effect of a broad range of chemical agents. We demonstrate the prediction capability of the sensor in identifying the nature of an unknown test sample from a combination of three chemical agents, namely, ethanol, pyrethroid, and hydrogen peroxide. This was achieved through a two-step process. The first step was experimentally achieved by in situ recording of the changes to the extracellular electrical activity from the sensing sites or the array of microelectrodes that form the platform for patterning neurons. Simultaneous optical characterization of the cell array during the sensing process was performed to identify the associated physiological changes. The second step was mathematical and was based on developing a library of signature patterns for a set of concentrations of the various combinations of the three chemical agents. Two variants of the nearest neighbor algorithm scheme - (a) partial distance search method, and (b) search tree method, were implemented for the accurate detection of all the components with varying concentrations in the test samples of unknown nature. This technique exhibits reliability in identification up to parts-per-billion (ppb) sensitivity. The capability of standardization of this technique for potential commercial applications is also discussed.

Action Potentials↗

PubMed1987

Transdermal scopolamine: effects of single and repeated patches upon psychological task performance.

Scopolamine and placebo transdermal patches were applied on alternating days to 12 normal volunteer subjects. Psychological performance tasks, physiological assessments, a subjective feeling state questionnaire, and a sleep questionnaire were completed each day. Transdermal scopolamine produced significant decrements in memory task performance, daytime feelings of alertness, ease of waking, and alertness following waking, while resting heart rates were lowered. Significant drug x patch number interaction effects were present with memory for new information, letter cancellation omission errors, rapid visual information processing reaction time, and self-rated ease of getting to sleep, but there was no consistent pattern to the changes following successive patches. Visual problems (blurred vision, longer visual near point) increased following successive scopolamine patches, but the changes in task performance were not related to these visual changes.

Administration, Cutaneous↗

PubMed1990

Phoneme discrimination using connectionist networks.

The application of connectionist networks to speech recognition is assessed using a set of eight representative phonetic discrimination problems chose with respect to a theory of phonetics. A connectionist network model called the temporal flow model (TFM) is defined which represents temporal relationships using delay links and permits general patterns of connectivity. It is argued that the model has properties appropriate for time varying signals such as speech. Networks are trained using gradient descent methods of iterative nonlinear optimization to reduce the mean-squared error between the actual and the desired response of the output units. Separate network solutions are demonstrated for all eight phonetic discrimination problems for one male speaker. The network solutions are analyzed carefully and are shown in every case to make use of known acoustic phonetic cues. The network solutions vary in the degree to which they make use of context-dependent cues to achieve phoneme recognition. The network solutions were tested on data not used for training and achieved an average accuracy of 99.5%. It is concluded that acoustic phonetic speech recognition can be accomplished using connectionist networks.

Algorithms↗