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PubMed1998

Detection of human antibodies using "convergent" combinatorial peptide libraries or "mixotopes" designed from a nonvariable antigen: application to the EBV viral capsid antigen p18.

We have previously described the use of synthetic combinatorial "convergent" libraries, or "mixotopes" as immunogens or as antigens to represent naturally hypervariable sequences. The success of this approach suggests that such a mixture of closely related peptides could, at least in part, conveniently represent a nonvariable epitope during its multiple interactions with an antibody population. To address this possibility, we have designed from a non-variable immunodominant peptide of the EBV-viral capsid antigen of 18 kD (VCAp18) a series of three mixotopes containing from 65,000 to 16 million combinatorial sequences. The reactivity of VCAp18 and its three derived mixotopes was examined in ELISA towards a collection of 74 human sera from documented EBV-negative or EBV-positive donors, and analyzed in terms of sensitivity and specificity. Following the observation that the two least degenerated mixotopes could improve the sensitivity of detection of some sera of low reactivity for VCAp18, we decided to combine each mixotope with the VCAp18 peptide. In the case of the least degenerated mixotope in combination with VCAp18, sensitivity and specificity for immunoenzymatic EBV-serodiagnosis, were enhanced to 100%. Our results suggest that synthetic "convergent" combinatorial peptide libraries or "mixotopes," designed from nonvariable antigens, could be useful adjuncts to an antigenic single-sequence peptide in immunoenzymatic serodiagnosis.

Amino Acid Sequence↗

PubMedDate not supplied

Limits of parallel processing: excitatory convergence of different information channels on single neurons in striate and extrastriate visual cortices.

1. It has been postulated that the distinct parallel retino-geniculo-cortical information channels characterizing visual pathways of virtually all mammals are selectively linked to parallel motion, colour and/or form information processing 'streams' distinguishable within the primary visual cortices, extrastriate cortical areas of occipital lobes and the temporal and parietal visual cortices. 2. Using selective pressure-blocking of the large-fibre channel (the so-called Y-channel) in the optic nerve of the cat, we have experimentally examined the 'selective excitatory parallel links' hypothesis. We conclude that the majority of neurons in the primary visual cortices (areas 17, 18) as well as in the two 'higher order' visual areas, area 21a and posteromedial lateral suprasylvian (PMLS) area, constituting, respectively, part of the 'form' and part of the 'motion' processing streams, receive their excitatory inputs from both Y- and non-Y-information channels. In areas 17, 18 and 21a (but not in PMLS area), there are, however, subpopulations of cells that apparently receive excitatory inputs from only one information channel. 3. Review of the relevant work on the macaque monkey suggests that the situation is similar in the primate: that is, there is a substantial degree of excitatory convergence of different retino-geniculo-cortical information channels on single neurons in the primary visual cortices and the extrastriate cortices constituting parts of the form/colour or the motion processing streams. 4. Despite this high degree of excitatory convergence of different information channels, the large-fibre channels (the Y-channel in the cat and the magnocellular or Y-like channel in macaque), are in both carnivores and primates the principal contributors to the motion processing cortical streams.

Animals↗

PubMed1993

Convergence of the Child Behavior Checklist with structured interview-based psychiatric diagnoses of ADHD children with and without comorbidity.

We evaluated the convergence of CBCL scales with the diagnosis of ADHD and comorbid disorders in 133 ADHD and 118 normal control boys, aged 6-17 years old. We evaluated the strength of association between each CBCL scale and structured-interview derived diagnoses with Total Predictive Value (TPV) and the odds-ratio (OR). Excellent convergence was found between the CBCL Attention Problems scale with the diagnosis of ADHD, between the Delinquent Behavior scale and the diagnosis of CD, and between the Anxiety/Depression scale and the diagnoses of Anxiety Disorders. These findings indicate that the CBCL could serve as a rapid and useful screening instrument to identify comorbid and non-comorbid cases of ADHD.

Adolescent↗

PubMed1989

The autonomic differentiation of emotions revisited: convergent and discriminant validation.

The convergent and discriminant validity of three models of physiological emotion specificity were compared. Forty-two female students served as subjects in a 2 (Context of emotional inductions: real-life, imagery) X 3 (Emotion: fear, anger, control) +1 (Happiness induced in real-life context) repeated measures design. The dependent measures included self-reports of emotion, Gottschalk-Gleser affect scores, back and forearm extensor EMG activity, body movements, heart period, respiration period, skin conductance, skin temperatures, pulse transit time, pulse volume amplitude, and blood volumes. Self-report data confirmed the generation of affective states in both contexts, as intended. Planned multivariate comparisons between physiological profiles established discriminant validity for fear and anger in the real-life context, whereas under imagery, emotion profiles were essentially equal. Convergent validity could not be substantiated. Implications for models of physiological specificity of emotion were discussed.

Adult↗

PubMed2003

Coherent accounts of coping with a chronic illness: convergences and divergences in family measurement using a narrative analysis.

Researchers and clinicians have shown increasing interest in family narratives as an avenue for accessing the family meaning-making process. In this study, we examine the convergences and divergences between narrative assessment, family self-report, and verbal accounts of family climate. Sixty-two families with a child with pediatric asthma were interviewed about the impact that asthma had on family life. These interviews were coded for narrative coherence, relationship expectations, and engagement with the interviewer. Primary caregivers were also interviewed using the Five Minute Speech Sample (FMSS) and completed self-report assessments of family functioning (Family Assessment Device [FAD]; Impact on the Family Scale [IOF]). Contrary to prediction, narrative coherence was higher in those cases where Emotional Over-involvement (EOI) was present on the FMSS. Narrative coherence and engagement with the interviewer were positively related to self-report of family problem solving, communication, and affective responsiveness as measured on the FAD. Divergences and convergences between different types of family measurement are discussed in light of meaning-making processes associated with coping with a chronic illness.

Adaptation, Psychological↗

PubMed1980

Organic convergence spasm.

Convergence spasm has frequently been reported as a hysterical manifestation. A case presenting with this sign and diphenylhydantoin intoxication is described. Other previously reported organic associations are discussed. Convergence spasm may be seen in association with significant organic disease of the nervous system affecting the cerebral hemispheres, the brain-stem, or both.

Adolescent↗

PubMed1997

Undergraduate training in the European Union. Convergence or divergence?

A survey of dental schools in the European Union was carried out for two main reasons. Firstly to promote the exchange of information in respect of curriculum objectives in the different countries and secondly to ascertain the differences in the interpretation of the 1978 EU sectoral directives for dental education and training. Out of 127 schools, only 30 responded, yet the information provided is of considerable importance. It demonstrates wide divergence in the interpretation of the 1978 Directives and methods of assessment of clinical competence. There is a considerable difference throughout Europe in hours devoted to the various subjects included in the Dental Directives. There is little evidence of convergence in methods of assessment or quality assurance. The survey demonstrates the difference in resources, levels of staff, availability of clinical training places, output in research and patient treatments throughout the European Union. The results question the effectiveness of the 1978 Dental Directives in promoting convergence of standards. As there is free movement of dentists throughout the European Union, it is concluded that a different approach may be necessary to ensure that all European Union dental graduates achieve comparable standards in their education and training.

Curriculum↗

PubMed2004

Convergent analysis of cDNA and short oligomer microarrays, mouse null mutants and bioinformatics resources to study complex traits.

Gene expression data sets have recently been exploited to study genetic factors that modulate complex traits. However, it has been challenging to establish a direct link between variation in patterns of gene expression and variation in higher order traits such as neuropharmacological responses and patterns of behavior. Here we illustrate an approach that combines gene expression data with new bioinformatics resources to discover genes that potentially modulate behavior. We have exploited three complementary genetic models to obtain convergent evidence that differential expression of a subset of genes and molecular pathways influences ethanol-induced conditioned taste aversion (CTA). As a first step, cDNA microarrays were used to compare gene expression profiles of two null mutant mouse lines with difference in ethanol-induced aversion. Mice lacking a functional copy of G protein-gated potassium channel subunit 2 (Girk2) show a decrease in the aversive effects of ethanol, whereas preproenkephalin (Penk) null mutant mice show the opposite response. We hypothesize that these behavioral differences are generated in part by alterations in expression downstream of the null alleles. We then exploited the WebQTL databases to examine the genetic covariance between mRNA expression levels and measurements of ethanol-induced CTA in BXD recombinant inbred (RI) strains. Finally, we identified a subset of genes and functional groups associated with ethanol-induced CTA in both null mutant lines and BXD RI strains. Collectively, these approaches highlight the phosphatidylinositol signaling pathway and identify several genes including protein kinase C beta isoform and preproenkephalin in regulation of ethanol- induced conditioned taste aversion. Our results point to the increasing potential of the convergent approach and biological databases to investigate genetic mechanisms of complex traits.

Animals↗

PubMed2006

Converging NBIC technologies for improving human performance: a critical assessment of the novelty and the prospects of the project.

This contribution focuses on two claims advanced by the proponents of the project of "Converging Technologies for Improving Human Performance." Firstly, it is maintained that this project represents something genuinely new and quite unique. Secondly, it is argued that the future prospects of the project are extraordinarily positive. In order to critically assess both claims this paper first focuses on the question of whether there is actually anything genuinely new about the project of improving human performance by means of converging NBIC technologies. In addition it is analyzed whether the project warrants that we be optimistic about its future prospects.

Biomedical Enhancement↗

PubMed1994

Prolonged preoperative prismatic treatment in alternating convergent squint.

Our 10-year retrospective study includes 178 children below the age of 10 years, operated for alternating convergent squint. Inclusion criteria were: Absence of amblyopia and an angle of squint less than 45 pdpt so that alignment of the eyes in only one operation could be expected. One hundred children received preoperatively a prismatic correction of the distance deviation for a period of 6-15 months; 78 cases were treated with glasses and occlusion. In the prism-treated group a significantly better alignment (p = 0.0001) with a motorial gain of 7-8 pdpt was observed 6 months after surgery; also better sensorial results with significantly (p = 0.0001) more cases of stable NRC or harmonious ARC and improved binocularity were achieved. Unlike the type of esotropia, the preexisting retinal correspondence significantly influenced the motorial outcome (p < 0.05). Fewer reoperations were necessary in the prism-treated group (p = 0.001). Our results indicate that a prolonged prismatic correction is an effective preoperative treatment in patients with alternating convergent squint.

Child↗

PubMed1977

Nasal field loss in kittens reared with convergent squint: neurophysiological and morphological studies of the lateral geniculate nucleus.

1. Recordings of single cells were made in layers A and A1 of the lateral geniculate nucleus of kittens raised with convergent squint in one eye, and morphological studies of cells representing the different parts of the visual fields in these layers were also made from histological sections.2. For the normal eye, cells receiving inputs from the nasal and temporal visual fields were evenly represented up to the periphery, whereas for the squinting eye, no cells which permitted quantitative studies of receptive field properties could be found in the periphery of the nasal field.3. The loss of nasal field, represented by the loss of functional cells in the LGN layer A1 fed by the squinting eye, depended on the severity of the squint. The greater the angle of convergent squint, the greater the loss of nasal field represented by the loss of functional cells.4. The cells fed by the squinting eye's temporal visual field retained their brisk function, although minor modifications in the receptive field organisation were apparent.5. The mean perikaryal size was smaller and the cell-density higher for cells in layers fed by the squinting eye. As found for the functional loss of cells, the shrinkage of perikaryal size and the increase of cell-density was smallest in the zones fed by the temporal visual field, and greatest in the zones fed by the peripheral nasal visual field.6. The functional and morphological changes in the cells in the LGN, which receive inputs from the nasal field of the squinting eye, are attributed to part of the temporal retina being hidden behind the bridge of the nose. It is proposed that this is a consequence of disuse atrophy, due to lack of stimulation during the sensitive period of development.

Action Potentials↗

PubMed1977

Nasal field loss in cats reared with convergent squint: behavioural studies.

1. The extent of the monocular visual field in cats reared with convergent squint in one eye was determined by a behavioural perimetry technique. 2. Significant reduction in the extent of the visual field was found in the squinting eyes. 3. The visual field defect is a graded one, located mainly in the nasal field, but in some cats extending into the temporal visual field. The defect includes a zone of absolute loss of response to stimuli at the extreme nasal field, adjacent areas of partial response and areas of 100% response in the periphery of the temporal field. 4. A direct relationship was found between the angle of horizontal deviation of the squinting eye and the amount of visual field loss: i.e. the larger the angle of squint, the greater the loss of nasal field. 5. It is suggested that the process leading to a loss in nasal visual field is independent of the loss of visual acuity in squinting cats, since the latter is not related to the angle of squint. 6. The significant loss in nasal visual field found by behavioural experiments in cats reared with a convergent squint thus correlates with comparable deficits found in the physiology and morphology of the lateral geniculate nucleus (Ikeda, Plant & Tremain, 1977), although the behaviourally determined loss of nasal field is greater than would be expected from the study of the response of the LGN neurones.

Animals↗

PubMed1982

The ultrastructure of cat fusimotor endings and their relationship to foci of sarcomere convergence in intrafusal fibres.

1. Six muscle spindle poles, five from experiments in which foci of sarcomere convergence had been observed during stimulation of fusimotor axons, were serially sectioned for light and electron microscopy. Every somatic motor terminal was studied in ultrathin sections at several levels.2. In all six poles static gamma axons, or presumed static gamma axons, supplying the static bag(2) fibre and/or chain fibres had no terminations on the dynamic bag(1) fibre. In five poles, the dynamic bag(1) fibre was selectively innervated by dynamic gamma or beta axons save in one case where a dynamic gamma axon also innervated one chain fibre.3. Seventy-seven motor endings were of four distinct ultrastructural types: ;m(a) plates' lay superficially on the surface of static bag(2) or chain fibres; ;m(b) plates' were deeply indented into dynamic bag(1) fibres; in ;m(c) plates', found on chain fibres only, the muscle surface was thrown into projecting fingers between which the axon terminals were embedded; one type ;m(d) plate' was found, fully indented into a long chain fibre. A few plates of intermediate form (m(ab)) were variants of m(a) and m(b) plates.4. The muscle membrane beneath both m(a) and m(b) plates was smooth, or had a few wide, shallow folds; m(c) plates usually had wide, shallow subjunctional folds; numerous deep, narrow folds were characteristic of the m(d) plate. The length of unmyelinated pre-terminal axon or the number of sole plate nuclei were not useful diagnostic features.5. Obvious foci of sarcomere convergence in the capsular sleeve region of dynamic bag(1) and static bag(2) fibres coincided with the location of motor plates. Additional contraction foci were observed in the extracapsular region of dynamic bag(1) fibres where there was no motor innervation; contraction occurs principally in the outer half of these fibres. No foci of contraction or motor plates were observed in the extracapsular region of static bag(2) fibres; contraction in these fibres is typically mid-polar.6. In some poles local contraction of chain fibres centred on the location of m(c) plates. In others, very localized contraction occurred distal to the sites of m(a) plates. Both m(a) and m(c) plates were never found on the same pole of a chain fibre.7. Dynamic gamma or beta axons end in m(b) plates, probably equivalent to p(2) plates. The concept of distinctly different p(1) and p(2) plates on dynamic bag(1) fibres, supplied by dynamic beta and gamma axons, respectively, is not supported by ultrastructural evidence.8. Some static gamma axons end in multiple m(a) plates which correspond with ;trail endings', or in single large m(a) plates, on static bag(2) or chain fibres. The m(c) plates are the terminations of other static gamma, or occasionally dynamic gamma, axons on chain fibres. Static beta axons probably end in m(d) plates on long chain fibres which may correspond with p(1) plates.9. It is proposed that there are two types of static gamma motoneurone, one terminating in m(a) plates and the other in m(c) plates, possibly directed preferentially towards static bag(2) fibres and chain fibres, respectively.

Animals↗

PubMed1993

Histamine activates Cl- and K+ currents in guinea-pig tracheal myocytes: convergence with muscarinic signalling pathway.

1. We investigated the effects of histamine on membrane currents and contractile state of isolated guinea-pig tracheal myocytes using perforated patch and whole-cell recording techniques. The effects of histamine were compared to those of acetylcholine (ACh) and caffeine. 2. During voltage clamp (Vhold = -60 mV), histamine elicited contraction and an inward current (Ihist) which was often followed by current oscillations. Ihist had a reversal potential (Vrev) of -9 +/- 3 mV. 3. Ihist was dependent on the Cl- gradient and was antagonized by the Cl- channel blocker niflumic acid. Vrev was more positive (+2 +/- 1 mV) when K(+)-selective currents were blocked by Cs+ and TEA. When all external Na+ was replaced with N-methyl-D-glucamine, there was a small reduction in the amplitude of Ihist. 4. The histamine-induced current was similar to that elicited by ACh and by caffeine with respect to time course, amplitude, and current-voltage relationship. Responses to histamine and to ACh were non-additive, consistent with a convergence of histaminergic and cholinergic signalling pathways. Ihist was antagonized by the H1 histaminergic receptor antagonist astemizole, but not by atropine. 5. When recorded using the perforated patch configuration, Ihist could be elicited repeatedly for more than 30 min. When cells were studied in the whole-cell configuration using a pipette solution containing 0.025 mM EGTA, the amplitude of Ihist was initially the same as that obtained using perforated patch but then decreased; the time required for the responses to decrease to 50% (t1/2) was 8.2 +/- 1.0 min. When 1 mM EGTA was included in the pipette solution (whole-cell configuration), the initial response to histamine was significantly decreased in size and t1/2 was reduced to 3.3 +/- 0.7 min. 6. The characteristics of the signalling pathway were examined in cells studied using the whole-cell configuration with 0.025 mM EGTA in the recording pipette. Heparin significantly reduced t1/2 to 4.3 +/- 0.8 min. GTP gamma S elicited inward current and oscillations; both effects were enhanced by histamine. GTP gamma S also reduced t1/2 to 1.4 +/- 0.1 min. Pertussis toxin did not alter the amplitude or time course of Ihist. 7. We conclude that in guinea-pig tracheal myocytes, binding of histamine to H1 receptors leads to release of Ca2+ from intracellular stores and subsequent activation of Cl- and K+ conductances as well as contraction. Furthermore, we demonstrate that ACh elicits similar physiological responses due to a convergence of the histaminergic and muscarinic signalling pathways.

Acetylcholine↗

PubMed2003

Convergent control of synaptic GABA release from rat dorsal horn neurones by adenosine and GABA autoreceptors.

Perforated patch clamp recordings were performed on cultured superficial neonatal rat dorsal horn (DH) spinal cord neurones in order to study the presynaptic modulation of GABA release at unitary synaptic connections. Since ATP can be coreleased with GABA at about two-thirds of GABAergic synapses between DH neurones, and can be rapidly metabolized to adenosine in the extracellular space, we investigated the potential role of A1 adenosine receptors and GABAB receptors which might function as inhibitory autoreceptors. Adenosine and GABAB receptor agonists reduced the amplitude of electrically evoked GABAergic inhibitory postsynaptic currents (eIPSCs) as well as the frequency of GABAergic miniature IPSCs, suggesting a presynaptic action of these substances. The actions of adenosine were blocked by the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). The effects of adenosine and GABAB agonists were occlusive, indicating a functional convergence of the signalling pathways engaged by A1 and GABAB receptors. A1 and GABAB antagonists increased the amplitude of eIPSCs in a supra-additive manner, suggesting a tonic activation of these receptors by ambient adenosine and GABA. Moreover, using trains of electrical stimulations, we were able to unravel a phasic (activity-dependent) activation of presynaptic A1 and GABAB autoreceptors only in the case of neurones coreleasing ATP and GABA, despite the presence of functional presynaptic A1 and GABAB receptors on all GABAergic DH neurones. This selective, convergent and activity-dependent inhibition of GABA release by A1 and GABAB autoreceptors might modulate the integrative properties of postsynaptic DH neurones under physiological conditions and/or during the development of pathological pain states.

Adenosine↗

PubMed2006

Convergence of multiple pelvic organ inputs in the rat rostral medulla.

Electrophysiological recordings were used to investigate the degree of pelvic/visceral convergent inputs onto single medullary reticular formation (MRF) neurons. A total of 94 MRF neurons responsive to bilateral electrical stimulation of the pelvic nerve (PN) in 12 urethane-anaesthetized male rats were tested for responses to mechanical stimulation of the urinary bladder, urethra, colon and penis, and electrical stimulation of the dorsal nerve of the penis (DNP) and abdominal branches of the vagus. Responses to distension of the bladder were found for 51% (n = 48) of the MRF neurons tested. Of these 48, 71% responded to urethral infusion, 81% responded to colon distension, 100% responded to penile stimulation (and DNP), and 85% responded to vagal stimulation, with 62% responding to stimulation of all four of these territories. This high degree of visceral convergence (i.e. 62%) in a subset of PN-responsive MRF neurons is significantly greater than for the subset of PN-responsive MRF neurons that did not respond to urinary bladder distension (i.e. out of the 46 remaining neurons, none responded to all four of the other pelvic/visceral stimuli combined). These results suggest that the neurons processing information from the urinary bladder at this level of the neural axis are likely to be important for mediating interactions between different visceral organs for the coordination of multiple pelvic/visceral functions.

Action Potentials↗

PubMed1974

Convergent morphological evolution detected by studying proteins of tree frogs in the Hyla eximia species group.

Protein studies have uncovered an apparent case of convergent evolution among North American tree frogs. The species Hyla eximia and Hyla regilla are so similar in external morphology that the "wrightorum" subspecies is assigned by some authorities to H. eximia and by others to H. regilla. Yet microcomplement fixation experiments show that "wrightorum" albumin, though virtually indistinguishable from authentic H. eximia albumin, differs as much from H. regilla albumin as from albumins of species outside the genus Hyla, such as Acris crepitans. The morphological resemblance of "wrightorum" to H. regilla is thus probably due to convergence.

Amino Acid Sequence↗

PubMed1996

Functional uncoupling of linked neurotransmitter effects by combinatorial convergence.

Physiological signaling pathways both diverge and converge-a single neurotransmitter can have multiple effects and multiple transmitters can have the same effects-in the same target cell. Divergence couples the effects of a transmitter together in a relatively fixed ratio. Different physiological circumstances may require a different ratio, however; the coupling must be made modifiable. This can be achieved through convergence. If two transmitters couple the effects in different ratios, then combinations of the transmitters can yield all intermediate ratios of the effects, thus functionally uncoupling them. This mechanism is analyzed in a well-understood, simple invertebrate neuromuscular circuit.

Animals↗