Social Cognition, Face Processing, and Oxytocin Receptor Single Nucleotide Polymorphisms in Typically Developing Children

Recent research has provided evidence of a link between behavioral measures of social cognition (SC) and neural and genetic correlates. Differences in face processing and variations in the oxytocin receptor (OXTR) gene have been associated with SC deficits and autism spectrum disorder (ASD) traits. Much work has examined the qualitative differences between those with ASD and typically developing (TD) individuals, but very little has been done to quantify the natural variation in ASD-like traits in the typical population. The present study examines this variation in TD children using a multidimensional perspective involving behavior assessment, neural electroencephalogram (EEG) testing, and OXTR genotyping. Children completed a series of neurocognitive assessments, provided saliva samples for sequencing, and completed a face processing task while connected to an EEG. No clear pattern emerged for EEG covariates or genotypes for individual OXTR single nucleotide polymorphisms (SNPs). However, SNPs rs2254298 and rs53576 consistently interacted such that the AG/GG allele combination of these SNPs was associated with poorer performance on neurocognitive measures. These results suggest that neither SNP in isolation is risk-conferring, but rather that the combination of rs2254298(A/G) and rs53576(G/G) confers a deleterious effect on SC across several neurocognitive measures. Copyright 2014. Published by Elsevier Ltd.

Effect of multislice acquisition on T1 and T2 measurements of articular cartilage at 3T

PURPOSE: The aim of this study was to investigate the effect of magnetization transfer on multislice T(1) and T(2) measurements of articular cartilage. MATERIALS AND METHODS: A set of phantoms with different concentrations of collagen and contrast agent (Gd-DTPA(2-)) were used for the in vitro study. A total of 20 healthy knees were used for the in vivo study. T(1) and T(2) measurements were performed using fast-spin-echo inversion-recovery (FSE-IR) sequence and multi-spin-echo (MSE) sequence, respectively, in both in vitro and in vivo studies. We investigated the difference in T(1) and T(2) values between that measured by single-slice acquisition and that measured by multislice acquisition. RESULTS: Regarding T(1) measurement, a large drop of T(1) in all slices and also a large interslice variation in T(1) were observed when multislice acquisition was used. Regarding T(2) measurement, a substantial drop of T(2) in all slices was observed; however, there was no apparent interslice variation when multislice acquisition was used. CONCLUSION: This study demonstrated that the adaptation of multislice acquisition technique for T(1) measurement using FSE-IR methodology is difficult and its use for clinical evaluation is problematic. In contrast, multislice acquisition for T(2) measurement using MSE was clinically applicable if inaccuracies caused by multislice acquisition were taken into account. J. Magn. Reson. Imaging 2007;26:109-117. (c) 2007 Wiley-Liss, Inc.

Visual vector inversion during memory antisaccades--a TMS study

In the memory antisaccade task, subjects are instructed to look at an imaginary point precisely at the opposite side of a peripheral visual stimulus presented short time previously. To perform this task accurately, the visual vector, i.e., the distance between a central fixation point and the peripheral stimulus, must be inverted from one visual hemifield to the other. Recent data in humans and monkeys suggest that the posterior parietal cortex (PPC) might be critically involved in the process of visual vector inversion. In the present study, we investigated the temporal dynamics of visual vector inversion in the human PPC by using transcranial magnetic stimulation (TMS). In six healthy subjects, single pulse TMS was applied over the right PPC during a memory antisaccade task at four different time intervals: 100 ms, 217 ms, 333 ms, or 450 ms after target onset. The results indicate that for rightward antisaccades, i.e., when the visual target was presented in the left screen-half, TMS had a significant effect on saccade gain when applied 100 ms after target onset, but not later. For leftward antisaccades, i.e., when the visual target was presented in the right screen-half, a significant TMS effect on gain was found for the 333 ms and 450 ms conditions, but not for the earlier ones. This double dissociation of saccade gain suggests that the initial process of vector inversion can be disrupted 100 ms after onset of the visual stimulus and that TMS interfered with motor saccade planning based on an inversed vector signal at 333 ms and 450 ms after stimulus onset.

The Effect of Respirator Wear on Blood Lactate During Maximal Exertion

The impact of a filtering half-face respirator and a half-face supplied air respirator use on blood lactate production was assessed during maximal exertion to determine if anaerobic strain increased compared to no respirator use. Twenty-eight participants performed a 30 second cycling Wingate anaerobic test (WAnT) wearing a half-face respirator. Blood lactate production was measured to evaluate if there was an increase in anaerobic strain from wearing a tight fitting half-face respirator compared to wearing no respirator. A supplied air respirator WAnT was then performed using 18 participants from the first experiment to evaluate if supplied air decreased anaerobic strain. Data from both experiments were compared to evaluate differences in the physiological effects due to respirator use during maximal exertion. A survey was administered following the second WAnT experiment to measure the participants' perception of acceptability and impact of supplied air respirator use in workplace. The blood lactate levels measured directly after the WAnT yielded lower overall mean values during the half-mask respirator trial (12.1 mmollL) and supplied air respirator trial (12.2 mmollL) than the no respirator trial (13.1 mmoI/L). However, differences in blood lactate levels were not statistically significant (p =0.597). Participants reported an average acceptability of 92.3% to wearing the supplied air respirator while performing light work. However, the average acceptability decreased as the exertion increased to moderate (78.8%) and heavy (46.6%) workloads. The supplied air respirator used provided no significant reduction in anaerobic strain within this study group compared to either the filtering half-face respirator or the no respirator condition. However, there were differences in physiological effects of respirators on each gender identified in this study. Further assessment of the anaerobic impact of respirators on each gender should be conducted.

Emotion recognition: The role of featural and configural face information

Several studies investigated the role of featural and configural information when processing facial identity. A lot less is known about their contribution to emotion recognition. In this study, we addressed this issue by inducing either a featural or a configural processing strategy (Experiment 1) and by investigating the attentional strategies in response to emotional expressions (Experiment 2). In Experiment 1, participants identified emotional expressions in faces that were presented in three different versions (intact, blurred, and scrambled) and in two orientations (upright and inverted). Blurred faces contain mainly configural information, and scrambled faces contain mainly featural information. Inversion is known to selectively hinder configural processing. Analyses of the discriminability measure (A′) and response times (RTs) revealed that configural processing plays a more prominent role in expression recognition than featural processing, but their relative contribution varies depending on the emotion. In Experiment 2, we qualified these differences between emotions by investigating the relative importance of specific features by means of eye movements. Participants had to match intact expressions with the emotional cues that preceded the stimulus. The analysis of eye movements confirmed that the recognition of different emotions rely on different types of information. While the mouth is important for the detection of happiness and fear, the eyes are more relevant for anger, fear, and sadness.

The effect of superiors' exogenous constraints on budget negotiations

In a world characterized by increasing pressure from financial and product markets, the question of how exogenous constraints affect internal coordination and control processes has become increasingly important. This experiment investigates how two exogenous constraints that superiors can face in budget negotiation settings, increased opportunity costs and financial pressure to meet unit targets, affect budget negotiations and subordinate effort. The results show that both constraints induce more cooperation, but in different ways. Financial pressure on the superior leads to more cooperative negotiation behavior by superiors and subordinates than increased opportunity costs. Specifically, subordinates do not take advantage of the superior's increased financial pressure to enforce lower budgets. After negotiation, both constraints strongly mitigate the negative effects of superior budget imposition on subordinate effort because exogenous constraints eliminate the effect of procedural fairness considerations on subordinate effort.

An Unscathed Past in the Face of Death: Mortality Salience Reduces Individuals’ Regrets

Folk wisdom and popular literature hold that, in the face of death, individuals tend to regret things in their lives that they have done or failed to do. Terror Management Theory (TMT), in contrast, allows for the prediction that individuals who are confronted with death try to minimize the experience of regret in order to retain a positive self-esteem. Three experiments put these competing perspectives to test. Drawing on TMT, we hypothesized and found that participants primed with their own death regret fewer things than control-group participants. This pattern of results cannot be attributed to differing types of regrets (Study 1). Furthermore, we provide evidence suggesting that the effect is not purely a product of cognitive mechanisms such as differing levels of construal (Study 2), cognitive contrast, or deficits (Study 3). Rather, the reported results are best explained in terms of a motivational coping mechanism: When death is salient, individuals strive to bolster as well as protect their self-esteem and accordingly try to minimize the experience of regret. The results add to our conceptual understanding of regret and TMT, and suggest that a multitude of lifestyle guidebooks need updating.

Effect of simulated ocean acidification on the acute toxicity of Cu and Cd to Tigriopus japonicus

Heavy metals pollution in marine environments has caused great damage to marine biological and ecological systems. Heavy metals accumulate in marine creatures, after which they are delivered to higher trophic levels of marine organisms through the marine food chain, which causes serious harm to marine biological systems and human health. Additionally, excess carbon dioxide in the atmosphere has caused ocean acidification. Indeed, about one third of the CO2 released into the atmosphere by anthropogenic activities since the beginning of the industrial revolution has been absorbed by the world's oceans, which play a key role in moderating climate change. Modeling has shown that, if current trends in CO2 emissions continue, the average pH of the ocean will reach 7.8 by the end of this century, corresponding to 0.5 units below the pre-industrial level, or a three-fold increase in H+ concentration. The ocean pH has not been at this level for several millions of years. Additionally, these changes are occurring at speeds 100 times greater than ever previously observed. As a result, several marine species, communities and ecosystems might not have time to acclimate or adapt to these fast changes in ocean chemistry. In addition, decreasing ocean pH has the potential to seriously affect the growth, development and reproduction reproductive processes of marine organisms, as well as threaten normal development of the marine ecosystem. Copepods are an important part of the meiofauna that play an important role in the marine ecosystem. Pollution of the marine environment can influence their growth and development, as well as the ecological processes they are involved in. Accordingly, there is important scientific value to investigation of the response of copepods to ocean acidification and heavy metals pollution. In the present study, we evaluated the effects of simulated future ocean acidification and the toxicological interaction between ocean acidity and heavy metals of Cu and Cd on T. japonicus. To accomplish this, harpacticoids were exposed to Cu and Cd concentration gradient seawater that had been equilibrated with CO2 and air to reach pH 8.0, 7.7, 7.3 and 6.5 for 96 h. Survival was not significantly suppressed under single sea water acidification, and the final survival rates were greater than 93% in both the experimental groups and the controls. The toxicity of Cu to T. japonicus was significantly affected by sea water acidification, with the 96h LC50 decreasing by nearly threefold from 1.98 to 0.64 mg/L with decreasing pH. The 96 h LC50 of Cd decreased with decreasing pH, but there was no significant difference in mortality among pH treatments. The results of the present study demonstrated that the predicted future ocean acidification has the potential to negatively affect survival of T. japonicus by exacerbating the toxicity of Cu. The calculated safe concentrations of Cu were 11.9 (pH 7.7) and 10.5 (pH 7.3) µg/L, which were below the class I value and very close to the class II level of the China National Quality Standard for Sea Water. Overall, these results indicate that the Chinese coastal sea will face a

Drivers in adopting adaptation strategies to face increased water scarcity in agriculture. A case study in Doñana (Spain) and Makueni (Kenya)

La agricultura es uno de los sectores más afectados por el cambio climático. A pesar de haber demostrado a lo largo de la historia una gran capacidad para adaptarse a nuevas situaciones, hoy en día la agricultura se enfrenta a nuevos retos tales como satisfacer un elevado crecimiento en la demanda de alimentos, desarrollar una agricultura sostenible con el medio ambiente y reducir las emisiones de gases de efecto invernadero. El potencial de adaptación debe ser definido en un contexto que incluya el comportamiento humano, ya que éste juega un papel decisivo en la implementación final de las medidas. Por este motivo, y para desarrollar correctamente políticas que busquen influir en el comportamiento de los agricultores para fomentar la adaptación a estas nuevas condiciones, es necesario entender previamente los procesos de toma de decisiones a nivel individual o de explotación, así como los efectos de los factores que determinan las barreras o motivaciones de la implementación de medidas. Esta Tesis doctoral trata de profundizar en el análisis de factores que influyen en la toma de decisiones de los agricultores para adoptar estrategias de adaptación al cambio climático. Este trabajo revisa la literatura actual y desarrolla un marco metodológico a nivel local y regional. Dos casos de estudio a nivel local (Doñana, España y Makueni, Kenia) han sido llevados a cabo con el fin de explorar el comportamiento de los agricultores hacia la adaptación. Estos casos de estudio representan regiones con notables diferencias en climatología, impactos del cambio climático, barreras para la adaptación y niveles de desarrollo e influencia de las instituciones públicas y privadas en la agricultura. Mientras el caso de estudio de Doñana representa un ejemplo de problemas asociados al uso y escasez del agua donde se espera que se agraven en el futuro, el caso de estudio de Makueni ejemplifica una zona fuertemente amenazada por las predicciones de cambio climático, donde adicionalmente la falta de infraestructura y la tecnología juegan un papel crucial para la implementación de la adaptación. El caso de estudio a nivel regional trata de generalizar en África el comportamiento de los agricultores sobre la implementación de medidas. El marco metodológico que se ha seguido en este trabajo abarca una amplia gama de enfoques y métodos para la recolección y análisis de datos. Los métodos utilizados para la toma de datos incluyen la implementación de encuestas, entrevistas, talleres con grupos de interés, grupos focales de discusión, revisión de estudios previos y bases de datos públicas. Los métodos analíticos incluyen métodos estadísticos, análisis multi‐criterio para la toma de decisiones, modelos de optimización de uso del suelo y un índice compuesto calculado a través de indicadores. Los métodos estadísticos se han utilizado con el fin de evaluar la influencia de los factores socio‐económicos y psicológicos sobre la adopción de medidas de adaptación. Dentro de estos métodos se incluyen regresiones logísticas, análisis de componentes principales y modelos de ecuaciones estructurales. Mientras que el análisis multi‐criterio se ha utilizado con el fin de evaluar las opciones de adaptación de acuerdo a las opiniones de las diferentes partes interesadas, el modelo de optimización ha tenido como fin analizar la combinación óptima de medidas de adaptación. El índice compuesto se ha utilizado para evaluar a nivel regional la implementación de medidas de adaptación en África. En general, los resultados del estudio ponen de relieve la gran importancia de considerar diferentes escalas espaciales a la hora de evaluar la implementación de medidas de adaptación al cambio climático. El comportamiento de los agricultores es diferente entre lugares considerados a una escala local relativamente pequeña, por lo que la generalización de los patrones del comportamiento a escalas regionales o globales resulta relativamente compleja. Los resultados obtenidos han permitido identificar factores determinantes tanto socioeconómicos como psicológicos y calcular su efecto sobre la adopción de medidas de adaptación. Además han proporcionado una mejor comprensión del distinto papel que desempeñan los cinco tipos de capital (natural, físico, financiero, social y humano) en la implementación de estrategias de adaptación. Con este trabajo se proporciona información de gran interés en los procesos de desarrollo de políticas destinadas a mejorar el apoyo de la sociedad a tomar medidas contra el cambio climático. Por último, en el análisis a nivel regional se desarrolla un índice compuesto que muestra la probabilidad de adoptar medidas de adaptación en las regiones de África y se analizan las causas que determinan dicha probabilidad de adopción de medidas. ABSTRACT Agriculture is and will continue to be one of the sectors most affected by climate change. Despite having demonstrated throughout history a great ability to adapt, agriculture today faces new challenges such as meeting growing food demands, developing sustainable agriculture and reducing greenhouse gas emissions. Adaptation policies planned on global, regional or local scales are ultimately implemented in decision‐making processes at the farm or individual level so adaptation potentials have to be set within the context of individual behaviour and regional institutions. Policy instruments can play a formative role in the adoption of such policies by addressing incentives/disincentives that influence farmer’s behaviour. Hence understanding farm‐level decision‐making processes and the influence of determinants of adoption is crucial when designing policies aimed at fostering adoption. This thesis seeks to analyse the factors that influence decision‐making by farmers in relation to the uptake of adaptation options. This work reviews the current knowledge and develops a methodological framework at local and regional level. Whilst the case studies at the local level are conducted with the purpose of exploring farmer’s behaviour towards adaptation the case study at the regional level attempts to up‐scale and generalise theory on adoption of farmlevel adaptation options. The two case studies at the local level (Doñana, Spain and Makueni, Kenya) encompass areas with different; climates, impacts of climate change, adaptation constraints and limits, levels of development, institutional support for agriculture and influence from public and private institutions. Whilst the Doñana Case Study represents an area plagued with water‐usage issues, set to be aggravated further by climate change, Makueni Case study exemplifies an area decidedly threatened by climate change where a lack of infrastructure and technology plays a crucial role in the uptake of adaptation options. The proposed framework is based on a wide range of approaches for collecting and analysing data. The approaches used for data collection include the implementation of surveys, interviews, stakeholder workshops, focus group discussions, a review of previous case studies, and public databases. The analytical methods include statistical approaches, multi criteria analysis for decision‐making, land use optimisation models, and a composite index based on public databases. Statistical approaches are used to assess the influence of socio‐economic and psychological factors on the adoption or support for adaptation measures. The statistical approaches used are logistic regressions, principal component analysis and structural equation modelling. Whilst a multi criteria analysis approach is used to evaluate adaptation options according to the different perspectives of stakeholders, the optimisation model analyses the optimal combination of adaptation options. The composite index is developed to assess adoption of adaptation measures in Africa. Overall, the results of the study highlight the importance of considering various scales when assessing adoption of adaptation measures to climate change. As farmer’s behaviour varies at a local scale there is elevated complexity when generalising behavioural patterns for farmers at regional or global scales. The results identify and estimate the effect of most relevant socioeconomic and psychological factors that influence adoption of adaptation measures to climate change. They also provide a better understanding of the role of the five types of capital (natural, physical, financial, social, and human) on the uptake of farm‐level adaptation options. These assessments of determinants help to explain adoption of climate change measures and provide helpful information in order to design polices aimed at enhancing societal support for adaptation policies. Finally the analysis at the regional level develops a composite index which suggests the likelihood of the regions in Africa to adopt farm‐level adaptation measures and analyses the main causes of this likelihood of adoption.

Maintenance of a somatotopic cortical map in the face of diminishing thalamocortical inputs

This study addresses the extent of divergence in the ascending somatosensory pathways of primates. Divergence of inputs from a particular body part at each successive synaptic step in these pathways results in a potential magnification of the representation of that body part in the somatosensory cortex, so that the representation can be expanded when peripheral input from other parts is lost, as in nerve lesions or amputations. Lesions of increasing size were placed in the representation of a finger in the ventral posterior thalamic nucleus (VPL) of macaque monkeys. After a survival period of 1–5 weeks, area 3b of the somatosensory cortex ipsilateral to the lesion was mapped physiologically, and the extent of the representation of the affected and adjacent fingers was determined. Lesions affecting less than 30% of the thalamic VPL nucleus were without effect upon the cortical representation of the finger whose thalamic representation was at the center of the lesion. Lesions affecting about 35% of the VPL nucleus resulted in a shrinkage of the cortical representation of the finger whose thalamic representation was lesioned, with concomitant expansion of the representations of adjacent fingers. Beyond 35–40%, the whole cortical representation of the hand became silent. These results suggest that divergence of brainstem and thalamocortical projections, although normally not expressed, are sufficiently great to maintain a representation after a major loss of inputs from the periphery. This is likely to be one mechanism of representational plasticity in the cerebral cortex.

Communicating strategically in the face of terrorism: The Spanish government’s response to the 2004 Madrid bombing attacks

With the re-emergence of insurgency tied to terrorism, governments need to strategically manage their communications. This paper analyzes the effect of the Spanish government’s messaging in the face of the Madrid bombing of March 11, 2004: unlike what happened with the 9/11 bombings in the USA and the 7/07 London attacks, the Spanish media did not support the government’s framing of the events. Taking framing as a strategic action in a discursive form (Pan & Kosicki, 2003), and in the context of the attribution theory of responsibilities, this research uses the “cascading activation” model (Entman, 2003, 2004) to explore how a framing contest was generated in the press. Analysis of the coverage shows that the intended government frame triggered a battle among the different major newspapers, leading editorials to shift their frame over the four days prior to the national elections. This research analyzes strategic contests in framing processes and contributes insight into the interactions among the different sides (government, parties, media, and citizens) to help bring about an understanding of the rebuttal effect of the government’s intended frame. It also helps to develop an understanding of the role of the media and the influence of citizens’ frames on media content.

Auditory-visual speech integration by prelinguistic infants: Perception of an emergent consonant in the McGurk effect

The McGurk effect, in which auditory [ba] dubbed onto [go] lip movements is perceived as da or tha, was employed in a real-time task to investigate auditory-visual speech perception in prelingual infants. Experiments 1A and 1B established the validity of real-time dubbing for producing the effect. In Experiment 2, 4(1)/(2)-month-olds were tested in a habituation-test paradigm, in which 2 an auditory-visual stimulus was presented contingent upon visual fixation of a live face. The experimental group was habituated to a McGurk stimulus (auditory [ba] visual [ga]), and the control group to matching auditory-visual [ba]. Each group was then presented with three auditory-only test trials, [ba], [da], and [deltaa] (as in then). Visual-fixation durations in test trials showed that the experimental group treated the emergent percept in the McGurk effect, [da] or [deltaa], as familiar (even though they had not heard these sounds previously) and [ba] as novel. For control group infants [da] and [deltaa] were no more familiar than [ba]. These results are consistent with infants'perception of the McGurk effect, and support the conclusion that prelinguistic infants integrate auditory and visual speech information. (C) 2004 Wiley Periodicals, Inc.

Unidirectional inversion of ibuprofen in Caco-2 cells: Developing a suitable model for presystemic chiral inversion study

Intestinal chiral inversion of ibuprofen is still lacking direct evidence. In a preliminary experiment, ibuprofen was found to undergo inversion in Caco-2 cells. This investigation was thus conducted to determine the characteristics and influence of some biochemical factors on the chiral inversion of ibuprofen in Caco-2 cells. The effects of substrate concentration (2.5-40 mu g/ml), cell density (0.5-2 x 10(6) cells/ well), content of serum (0-20%), coexistence of S ibuprofen (corresponding doses), sodium azide (10mm), exogenous Coenzyme A (CoA) (0.1 - 0.4 mm),. and palmitic acid (5-25 mu m) on inversion were examined. A stereoselective HPLC method based on the Chromasil-CHI-TBB column was developed for quantitative analysis of the drug in cell culture medium. The inversion ratio (F-i) and elimination rate constant were calculated as the indexes of inversion extent. Inversion of ibuprofen in Caeo-2 cells was found to be both dose and cell density dependent, indicating saturable characteristics. Addition of serum significantly inhibited the inversion, to an extent of 2.7 fold decrease at 20% content. Preexistence of S enantiomer exerted a significant inhibitory effect (p < 0.01 for all tests). Sodium azide decreased the inversion ratio from 0.43 to 0.32 (p < 0.01). Exogenous CoA and palmitic acid significantly promoted the inversion at all tested doses (p < 0.01 for all tests). This research provided strong evidence to the capacity and capability of intestinal chiral inversion. Although long incubation times up to 120 h were required, Caco-2 cells should be a suitable model for chiral inversion research of 2-APAs considering the human-resourced and well-defined characteristics from the present study.

The evolutionary history of Symbiodinium and scleractinian hosts - Symbiosis, diversity, and the effect of climate change

Marine invertebrates representing at least five phyla are symbiotic with dinoflagellates from the genus Symbiodinium. This group of single-celled protists was once considered to be a single pandemic species, Symbiodinium microadriaticum. Molecular investigations over the past 25 years have revealed, however, that Symbiodinium is a diverse group of organisms with at least eight (A-H) divergent clades that in turn contain multiple molecular subclade types. The diversity within this genus may subsequently determine the response of corals to normal and stressful conditions, leading to the proposal that the symbiosis may impart unusually rapid adaptation to environmental change by the metazoan host. These questions have added importance due to the critical challenges that corals and the reefs they build face as a consequence of current rapid climate change. This review outlines our current understanding of the diverse genus Symbiodinium and explores the ability of this genus and its symbioses to adapt to rapid environmental change. (c) 2006 Rubel Foundation, ETH Zurich. Published by Elsevier GmbH. All rights reserved.

The heteromeric 5-HT3A/B receptor:the effect of 5-HT3B subunits on receptor structure and ligand recognition

The 5-HT3 receptors are members of the cys-loop family of ligand-gated ion channels. Two functional subtypes are known, the homomeric 5HT3A and the heteromeric 5HT3A/B receptors, which exhibit distinct biophysical characteristics but are difficult to differentiate pharmacologically. Atomic force microscopy has been used to determine the stoichiometry and architecture of the heteromeric 5HT3A/B receptor. Each subunit was engineered to express a unique C-terminal epitope tag, together with six sequential histidine residues to facilitate nickel affinity purification. The 5-HT3 receptors, ectopically expressed in HEK293 cells, were solubilised, purified and decorated with antibodies to the subunit specific epitope tags. Imaging of individual receptors by atomic force microscopy revealed a pentameric arrangement of subunits in the order BBABA, reading anti-clockwise when viewed from the extracellular face. Homology models for the heteromeric receptor were then constructed using both the electron microscopic structure of the nicotinic acetylcholine receptor, from Torpedo marmorata, and the X-ray crystallographic structure of the soluble acetylcholine binding protein, from Lymnaea stagnalis, as templates. These homology models were used, together with equivalent models constructed for the homomeric receptor, to interpret mutagenesis experiments designed to explore the minimal recognition differences of both the natural agonist, 5-HT, and the competitive antagonist, granisetron, for the two human receptor subtypes. The results of this work revealed that the 5-HT3B subunit residues within the ligand binding site, for both the agonist and antagonist, are accommodating to conservative mutations. They are consistent with the view that the 5-HT3A subunit provides the principal and the 5-HT38 subunit the complementary recognition interactions at the binding interface.