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PubMed2000

A role for the C3a anaphylatoxin receptor in the effector phase of asthma.

Asthma is a chronic inflammatory disease of the airways and lung mucosa with a strong correlation to atopy and acquired (IgE) immunity. However, many features of bronchial asthma, such as smooth muscle contraction, mucus secretion and recruitment of inflammatory cells, are consistent with the actions of complement anaphylatoxins, in particular C3a and C5a. Complement activation forms a central core of innate immune defence against mucosal bacteria, viruses, fungi, helminths and other pathogens. As a system of 'pattern-recognition molecules', foreign surface antigens and immune complexes lead to a proteolytic cascade culminating in a lytic membrane attack. The anaphylatoxins C3a and C5a are liberated as activation byproducts and are potent pro-inflammatory mediators that bind to specific cell surface receptors and cause leukocyte activation, smooth muscle contraction and vascular permeability. Here we show that in a murine model of allergic airway disease, genetic deletion of the C3a receptor protects against the changes in lung physiology seen after allergen challenge. Furthermore, human asthmatics develop significant levels of ligand C3a following intra-pulmonary deposition of allergen, but not saline. We propose that, in addition to acquired immune responses, the innate immune system and complement (C3a in particular) are involved in the pathogenesis of asthma.

Animals↗

PubMed2004

Face processing in humans is compatible with a simple shape-based model of vision.

Understanding how the human visual system recognizes objects is one of the key challenges in neuroscience. Inspired by a large body of physiological evidence, a general class of recognition models has emerged, which is based on a hierarchical organization of visual processing, with succeeding stages being sensitive to image features of increasing complexity. However, these models appear to be incompatible with some well-known psychophysical results. Prominent among these are experiments investigating recognition impairments caused by vertical inversion of images, especially those of faces. It has been reported that faces that differ 'featurally' are much easier to distinguish when inverted than those that differ 'configurally'; a finding that is difficult to reconcile with the physiological models. Here, we show that after controlling for subjects' expectations, there is no difference between 'featurally' and 'configurally' transformed faces in terms of inversion effect. This result reinforces the plausibility of simple hierarchical models of object representation and recognition in the cortex.

Face↗

PubMedDate not supplied

Chronobiology of human blood pressure in the light of static (room-restricted) automatic monitoring.

Systematic 24-h automatic physiologic monitoring has obvious merits, even without rhythmometry. It can lead more readily to the recognition of odd-hour blood pressure elevation (e.g., of 'evening' or 'morning' hypertension). Such a condition can constitute an initial diagnosis or it may be found under treatment that may seem to be satisfactory if its effects are assessed only on the basis of a conventional check at a casual, possibly 'wrong' time. The mere inspection of a 24-h record, however, does not necessarily allow one to make objective quantitative global statements as to a change in pattern, e.g., after a given intervention. This paper illustrates how by rhythmometry, some of the uncertainties of a subjective interpretation of a record may be removed by practitioners of medicine, as well as basic scientists interested in mechanisms of blood pressure variability. This is possible since a large part of blood pressure variability can be accounted for by its circadian periodic behavior. We herein present a methodology for data collection and analysis that allows the objective quantification of blood pressure rhythm parameters in health and disease and the derivation of reference standards for such parameters. The chronobiologic approach thus makes it possible to define 'hypertension' objectively, and to distinguish between 'mesor-' and 'amplitude-hypertension', i.e., between an elevation in overall mean and one in the predictable extent of variability. Moreover, chronobiology has shown that mesor-hypertension may be preceded by an elevation in circadian amplitude only (amplitude-hypertension). Parameter tests readily allow the assessment, in relation to an objective reference standard, of these conditions, with a defined probability. Similarly, response to drug or non-drug therapy can be established and a given intervention optimized by timing treatment. Using chronobiologic tools in cardiovascular research provides new insights into possible mechanisms underlying mesor- and amplitude-hypertension. The teaching of the chronobiology of blood pressure and autorhythmometry in schools has been proven to be feasible and has been recommended as a step toward self-help for health care.

Adolescent↗

PubMed2003

Steroid ring hydroxylation patterns govern cooperativity in human bile acid binding protein.

Human ileal bile acid binding protein (I-BABP) is a member of the intracellular lipid binding protein family. This protein is thought to function in the transcellular transport and enterohepatic circulation of bile salts. Human I-BABP binds two molecules of glycocholate, the physiologically most abundant bile salt, with modest intrinsic affinity but a remarkably high degree of positive cooperativity. Here we report a calorimetric analysis for the binding of a broad panel of bile salts to human I-BABP. The interaction of I-BABP with nine physiologically relevant derivatives of cholic acid, chenodeoxycholic acid, and deoxycholic acid in their conjugated (glycine and taurine) and unconjugated forms was monitored by isothermal titration calorimetry. All bile salts bound to I-BABP with a 2:1 stoichiometry and similar overall affinity, but the derivatives of cholic acid displayed much higher Hill coefficients, a measure of macroscopic positive cooperativity. To test whether the cooperativity was dependent on individual structural features of the bile salt side chain, a series of side-chain-extended bile salts that lacked a hydrogen bond donor or acceptor at C-24 were chemically synthesized. These synthetic variants exhibited the same energetic and cooperativity profile as the naturally occurring bile salts. Our findings indicate that cooperativity in bile salt-I-BABP recognition is governed by the pattern of steroid B- and C-ring hydroxylation and not the presence or type of side-chain conjugation.

Binding Sites↗

PubMed2007

Serine/threonine kinase PKR: a sentinel kinase that discriminates a signaling pathway mediated by TLR4 from those mediated by TLR3 and TLR9.

Cells of the innate immune system discriminate between "noninfectious self" and "infectious nonself" via pattern recognition receptors known as Toll-like receptors (TLRs). Though TLRs and the related interleukin 1 receptors share considerable homology in their cytoplasmic domains and adaptor molecules, signaling cascades may substantially differ from one another depending on the adaptor proteins recruited. Here we show that ectopic overexpression of catalytically inactive dominant-negative PKR expression system suppressed NF- kappa B activation mediated by TLR3, TLR9, TNF receptor 1 and 2 (TNF-R 1/2), but not by TLR4. Physiological relevance of the observations described here are discussed.

Animals↗

PubMed2003

Reductions in phenomenological, physiological and attentional indices of depressive mood after 2 Hz rTMS over the right parietal cortex in healthy human subjects.

Research into emotion and emotional disorders by repetitive transcranial magnetic stimulation (rTMS) has largely been restricted to the prefrontal regions. There is, however, also evidence for the parietal cortex being implicated in emotional (dys-)functioning. Here we used rTMS to investigate a role of the right parietal cortex in depression. In a placebo-controlled design, 2 Hz rTMS at 90% of the individual motor threshold (MT) was applied over the right parietal cortex of eight healthy subjects for 20 min continuously. Effects on mood, autonomic activity and motivated attention were investigated. Significant reductions in depressive mood were observed immediately following and 30 min after stimulation. Moreover, these findings were objectified by a concurring pattern of autonomically mediated changes in the attentional processing of angry facial expressions. These data suggest a role for the right parietal cortex in affective brain circuits regulating phenomenological, physiological and attentional aspects of depressive functioning.

Adult↗

PubMed1989

Sequential ideal-observer analysis of visual discriminations.

Visual stimuli contain a limited amount of information that could potentially be used to perform a given visual task. At successive stages of visual processing, some of this information is lost and some is transmitted to higher stages. This article describes a new analysis, based on the concept of the ideal observer in signal detection theory, that allows one to trace the flow of discrimination information through the initial physiological stages of visual processing, for arbitrary spatio-chromatic stimuli. This ideal-observer analysis provides a rigorous means of measuring the information content of visual stimuli and of assessing the contribution of specific physiological mechanisms to discrimination performance. Here, the analysis is developed for the physiological mechanisms up to the level of the photoreceptor. It is shown that many psychophysical phenomena previously attributed to neural mechanisms may be explained by variations in the information content of the stimuli and by preneural mechanisms.

Attention↗

PubMed1983

Effects of exposure to lines of one or two orientations on different cell types in striate cortex of cat.

We raised cats using goggles to control early visual exposure (stripe-rearing). Four conditions were used: (a), both eyes exposed to 0 degrees lines, (b), both eyes exposed to 90 degree lines, (c), one eye exposed to 45 degree lines, the other to 135 degree lines, (d), one eye exposed to 0 degree lines, the other to 90 degree lines. At the completion of the rearing, we recorded extracellularly from single cells in striate cortex (area 17) of these animals; circular statistics were used to analyse the distribution of the orientation preferences of neurones recorded. Exposure to either one or two stimulus orientations produced a significant bias in the distribution of the orientation preferences of cells recorded. We found no more non-selective cells in cats exposed to one orientation (15%) than in cats exposed to two orientations (14%). We found about the same mean proportion of binocular cells in cats exposed to one orientation (27%) as in cats exposed to two orientations (24%). Cells were comparable in orientation selectivity in cats exposed to one orientation (mean half-width at half-height = 37 degrees) and in cats exposed to two orientations (mean half-width at half-height = 34 degrees). The effects of the rearing depended upon the receptive field properties of the cells. For cells with narrow receptive fields and low cut-off velocities, the rearing produced no bias in the distribution of the orientation preferences; for all other groups of cells the rearing produced a bias toward the exposed orientation. In addition, the cells with narrow receptive fields and low cut-off velocities were more finely tuned for orientation than the remaining cells. We conclude that there are cell types in the striate cortex of the cat which differ in their susceptibility to the effects of stripe-rearing; these cell types can be discriminated on the basis of their physiological characteristics. We can compare these cell types with morphologically identified cell types that also differ in their susceptibility to the effects of stripe-rearing.

Animals↗

PubMed1992

Ambulatory measurement of oesophageal function: clinical use of a new pH and motility recording system.

Conventional oesophageal manometric studies are open to criticism in that they take place on fasted immobile subjects in the artificial setting of a motility laboratory. A new 24-h pH and motility recording system combined with computerized data analysis was used to study patients with gastro-oesophageal reflux disease and oesophageal motor abnormalities under ambulant conditions. Acid reflux episodes were found to be precipitated by a variety of events with recognizable pressure patterns. Acid clearance abnormalities were demonstrated in patients with erosive oesophagitis but were confined to those with abnormal oesophageal motor function. Improved diagnostic accuracy was demonstrated in the recognition of oesophageal motor disorders.

Circadian Rhythm↗

PubMed1979

Pseudodysrhythmias in ambulatory ECG monitoring.

Artifacts mimicking a variety of dysrhythmias occur relatively frequently in ambulatory ECG (Holter) monitoring records. Proper interpretation is imperative if serious therapeutic errors are to be avoided. Two-channel recording systems may facilitate recognition of some, but not all, of these artifacts. Pseudodysrhythmias may mimic paroxysmal supraventricular tachycardia and atrial fibrillation, atrial dissociation, extrasystoles, and sinus pauses. There are several causes of pseudodysrhythmias. Failure to recognize these patterns may result in serious errors in patient management.

Ambulatory Care↗

PubMed1993

Effect of the cold pressor test in healthy and hyperacid subjects.

The aim of this study was to estimate the effects of the cold pressor test (CPT) on hemodynamic changes and to analyze the differences in the changes between normal and hyperacid subjects. Twelve healthy volunteers and 12 hyperacid patients were studied. The different hemodynamic parameters (basic impedance, ZO; heart rate, HR; systolic and diastolic blood pressure, RRs and RRd; ventricular ejection time, VET; stroke volume, SV; cardiac output, CO; rate-pressure-product, RPP) were measured and calculated with the impedance cardiographic method (ICG). The changes of hemodynamic parameters (HR, RRs, RRd, VET, SV, CO, RPP) were well-recorded by this method. The data were analyzed with unpaired t-tests and the multivariate statistical method, pattern recognition by independent multicategory analysis (PRIMA). There were significant differences in changes of ZO, HR (P < 0.05), RRs, RRd, SV, CO and VET (P < 0.01) and subjects in the normal and hyperacid groups could be well separated by the PRIMA method.

Adult↗

PubMed1977

Objective determination of human visual acuity: pattern evoked potentials.

The natural visual acuities of 15 adult persons were predicted on the basis of changes in visual evoked potentials (VEP's) to flashed patterns of various sized dots. An objective method was used to quantify the VEP's, based on the minimum-sized stimulus that would elicit a pattern VEP- the VEP pattern threshold. This measure was highly correlated with recognition and resolution measures of perceptual visual acuity (r's as high as 0.89). The regression equation between the VEP measures and predicted perceptual measures of acuity enabled the objective estimation of perceptual acuity to within +/- 0.29 decimal units.

Adult↗

PubMed1981

Nutritional Assessment.

An abundant food supply has brought with it problems of overnutrition in Australia, but has not precluded problems of undernutrition and, indeed, overnutrition and undernutrition may coexist. "Dysnutrition" accounts for, or is associated with considerable morbidity and mortality in Australia. Nutritional assessment, therefore, is as important as other components of patient assessment. The approaches to nutritional assessment include: (i) identification of the individual at risk; (ii) eliciting relevant symptoms and signs; (iii) ascertaining to patients' food and nutrition knowledge and beliefs; (iv) establishing recent and remote food intake patterns: (v) anthropometry; and (vi) various laboratory investigations. The early recognition of excessive adiposity is likely to be a valuable contribution to preventive medicine. In hospital practice, the early recognition of protein energy malnutrition is likely to reduce the duration of hospital stay and morbidity and mortality rates.

Adult↗

PubMed2005

Generation of functional ion-channel tools by E3 targeting.

Here we describe a strategy for generating ion-channel inhibitors. It takes advantage of antibody specificity combined with a pattern recognition approach that targets the third extracellular region (E3) of a channel. To test the concept, we first focused on TRPC5, a member of the transient receptor potential (TRP) calcium channel family, the study of which has been hindered by poor pharmacological tools. Extracellular application of E3-targeted anti-TRPC5 antibody led to a specific TRPC5 inhibitor, enabling TRPC5 to be distinguished from its closest family members, and TRPC5 function to be explored in a relatively intractable physiological system. E3 targeting was further applied to voltage-gated sodium channels, leading to discovery of a subtype-specific inhibitor of Na(V)1.5. These examples illustrate the potential power of E3 targeting as a systematic method for producing gene-type specific ion-channel inhibitors for use in routine assays on cells or tissues from a range of species and having therapeutic potential.

Antibodies, Monoclonal↗

PubMed1997

Concentric orientation summation in human form vision.

Psychophysical data demonstrate that orientation information in concentric, random-dot Glass patterns is summed linearly to extract a global form percept. Surprisingly, no such global pooling was found for Glass patterns with parallel structure. A simple neural model explains these results and agrees with recent V4 single unit physiology. As V4 provides the major input to IT, global concentric units may play an important role in analyzing complex images such as faces. In support of this possibility, deficits in the perception of concentric Glass patterns have recently been linked to prosopagnosia.

Humans↗

PubMed2026

Single-cell transcriptomic landscape of the southern green stink bug (Nezara viridula) midgut.

BACKGROUND: The southern green stink bug (SGSB), Nezara viridula, is a globally distributed hemipteran pest that damages many economically important crops. Its midgut supports digestion, defense, symbiosis, and interactions with orally delivered control agents, yet the cellular composition of this tissue remains poorly characterized. We therefore developed a single-cell transcriptomic atlas of the N. viridula midgut. RESULTS: Single-cell RNA sequencing of two biological replicates yielded a quality-filtered data set of 13,763 cells. Unsupervised clustering identified 12 transcriptionally distinct populations with putative annotations, including a stem cell/enteroblast (SC/EB)-like population, seven enterocyte-related populations, goblet-like cells, enteroendocrine cells, visceral muscle cells, and an extracellular-matrix-associated epithelial population. Enterocyte-related populations accounted for more than 77% of recovered cells. Putative annotations were assigned primarily from marker gene enrichment and homology to markers reported in other insects. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses identified population-associated functional enrichment patterns, and pseudotime analysis suggested transcriptional relationships between the SC/EB-like population and several enterocyte- and secretory-associated populations without establishing developmental lineages. Immune- and defense-associated transcripts were preferentially enriched in the pEC2 population, and genes associated with symbiont recognition, insecticide action, xenobiotic transport, and orally delivered double-stranded RNA showed population-biased expression. Descriptive comparisons with published insect midgut data sets identified shared and data-set-specific patterns among annotated populations. CONCLUSION: This atlas provides the first single-cell transcriptomic resource for a stink bug midgut and establishes a descriptive cellular framework for SGSB midgut biology. The dataset prioritizes candidate genes and cell populations for future spatial validation, functional testing, and studies of hemipteran midgut physiology, symbiosis, immunity, and pest-management-relevant traits. © 2026 Society of Chemical Industry.

Nezara viridula↗

PubMed1998

Extraction of perceptually salient contours by striate cortical networks.

We present a cortical-based model for computing the perceptual salience of contours embedded in noisy images. It has been suggested that horizontal intra-cortical connections in primary visual cortex may modulate contrast detection thresholds and pre-attentive "pop-out". In our model, horizontal connections mediate context-dependent facilitatory and inhibitory interactions among oriented cells. Strongly facilitated cells undergo temporal synchronization; and perceptual salience is determined by the level of synchronized activity. The model accounts for a range of reported psychophysical and physiological effects of contour salience. In particular, the model proposes that intrinsic properties of synchronization account for the increased salience of smooth, closed contours. Application of the model to real images is demonstrated.

Contrast Sensitivity↗

PubMed2003

The perception of emotional chimeric faces in patients with depression, mania and unilateral brain damage.

BACKGROUND: Judgements made on chimeric faces elicit reliably a perceptual bias to the left hemispace, presumed to be due to right hemisphere dominance for emotional processes. Major depressive illness has been shown to attenuate this bias. The aim of this work was to examine lateral perceptual bias in bipolar I and II patients in a hypomanic state and unipolar depressed patients and those with unilateral hemisphere damage following stroke. METHOD: Sixty patients with DSM-IV affective disorder (30 bipolar I or II, currently hypomanic, 30 unipolar depressives), 30 right brain-damaged patients, 30 left brain-damaged patients and 30 healthy controls were given the Happy-Sad Chimeric Faces Test. RESULTS: Right hemisphere damaged and unipolar depressed patients both showed a significantly reduced left hemispatial bias (LHB) compared to controls, bipolars and left brain-damaged patients. No significant difference in mean LHB between controls and both hypomanics and left brain-damaged patients was found. There was no significant association between LHB and clinical variables. CONCLUSIONS: The results suggest a physiological distinction between bipolar and unipolar depression. The significantly diminished left hemifacial bias in depressed patients suggests right hemisphere dysfunction.

Aged↗