Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.

Livelihoods and Vulnerability in the Arid and Semi-Arid Lands of Southern Africa: Exploring the links between ecosystem services and poverty alleviation

This book sets out the findings of research conducted into the links between ecosystem services and poverty alleviation in Southern Africa. It follows from extensive primary research conducted in the region, as well as intensive engagement with researchers, policy-makers and relevant institutions in several countries in southern Africa, as part of the Ecosystem Services and Poverty Alleviation Programme led by DFI, NERC and ESRC.

Abstract platforms of computation

Computational formalisms have been pushing the boundaries of the field of computing for the last 80 years and much debate has surrounded what computing entails; what it is, and what it is not. This paper seeks to explore the boundaries of the ideas of computation and provide a framework for enabling a constructive discussion of computational ideas. First, a review of computing is given, ranging from Turing Machines to interactive computing. Then, a variety of natural physical systems are considered for their computational qualities. From this exploration, a framework is presented under which all dynamical systems can be considered as instances of the class of abstract computational platforms. An abstract computational platform is defined by both its intrinsic dynamics and how it allows computation that is meaningful to an external agent through the configuration of constraints upon those dynamics. It is asserted that a platform’s computational expressiveness is directly related to the freedom with which constraints can be placed. Finally, the requirements for a formal constraint description language are considered and it is proposed that Abstract State Machines may provide a reasonable basis for such a language.

Ethanol elicits and potentiates nociceptor responses via the vanilloid receptor-1

The vanilloid receptor-1 (VR1) is a heat-gated ion channel that is responsible for the burning sensation elicited by capsaicin. A similar sensation is reported by patients with esophagitis when they consume alcoholic beverages or are administered alcohol by injection as a medical treatment. We report here that ethanol activates primary sensory neurons, resulting in neuropeptide release or plasma extravasation in the esophagus, spinal cord or skin. Sensory neurons from trigeminal or dorsal root ganglia as well as VR1-expressing HEK293 cells responded to ethanol in a concentration-dependent and capsazepine-sensitive fashion. Ethanol potentiated the response of VR1 to capsaicin, protons and heat and lowered the threshold for heat activation of VR1 from approximately 42 degrees C to approximately 34 degrees C. This provides a likely mechanistic explanation for the ethanol-induced sensory responses that occur at body temperature and for the sensitivity of inflamed tissues to ethanol, such as might be found in esophagitis, neuralgia or wounds.

Socially anxious mothers’ narratives to their children, and their relation to child representations and adjustment

Anxious mothers’ parenting, particularly transfer of threat information, has been considered important in their children’s risk for social anxiety disorder (SAnxD), and maternal narratives concerning potential social threat could elucidate this contribution. Maternal narratives to their pre-school 4-5 year-old children, via a picture book about starting school, were assessed in socially anxious (N=73), and non-anxious (N=63) mothers. Child representations of school were assessed via Doll Play (DP). After one school term, mothers (CBCL) and teachers (TRF) reported on child internalizing problems, and child SAnxD was assessed via maternal interview. Relations between these variables, infant behavioral inhibition, and attachment, were examined. Socially anxious mothers showed more negative (higher threat attribution), and less supportive (lower encouragement) narratives, than controls, and their children’s DP representations, SAnxD and CBCL scores were more adverse. High narrative threat predicted child SAnxD; lower encouragement predicted negative child CBCL scores and, particularly for behaviorally inhibited children, TRF scores and DP representations. In securely attached children, CBCL scores and risk for SAnxD were affected by maternal anxiety and threat attributions, respectively. Low encouragement mediated the effects of maternal anxiety on child DP representations, and CBCL scores. Maternal narratives are affected by social anxiety, and contribute to adverse child outcome.

Diverse mechanisms underlying the regulation of ion channels by carbon monoxide

Carbon monoxide is firmly established as an important, physiological signalling molecule as well as a potent toxin. Through its ability to bind metal-containing proteins it is known to interfere with a number of intracellular signalling pathways, and such actions can account for its physiological and pathological effects. In particular, CO can modulate the intracellular production of reactive oxygen species, nitric oxide and cGMP levels, as well as regulate MAP kinase signalling. In this review, we consider ion channels as more recently discovered effectors of CO signalling. CO is now known to regulate a growing number of different ion channel types, and detailed studies of the underlying mechanisms of action are revealing unexpected findings. For example, there are clear areas of contention surrounding its ability to increase the activity of high conductance, Ca2+ -sensitive K+ channels. More recent studies have revealed the ability of CO to inhibit T-type Ca2+ channels and have unveiled a novel signalling pathway underlying tonic regulation of this channel. It is clear that the investigation of ion channels as effectors of CO signalling is in its infancy, and much more work is required to fully understand both the physiological and the toxic actions of this gas. Only then can its emerging use as a therapeutic tool be fully and safely exploited.

Bringing export performance metrics into Annual Reports: the APEV scale and the PERFEX scorecard

Annual company reports rarely distinguish between domestic and export market performance and even more rarely provide information about annual indicators of a specific export venture's performance. In this study, the authors develop and test a new measure for assessing the annual performance of an export venture (the APEV scale). The new measure comprises five dimensions: (1) annual export venture financial performance, (2) annual export venture strategic performance, (3) annual export venture achievement, (4) contribution of the export venture to annual exporting operations, and (5) satisfaction with annual export venture overall performance. The authors use the APEV scale to generate a scorecard of performance in exporting (the PERFEX scorecard) to assess export performance at the corporate level while comparatively evaluating all export ventures of the firm. Both the scale and the scorecard could help disclose export venture performance and could be useful instruments for annual planning, management, monitoring, and improvement of exporting programs.

The STEP scale: a measure of short-term export performance improvement

This article is a direct response to a recent observation in the literature that managers appear to be short-term oriented in their assessment of the performance of an export venture (Madsen 1998). On the basis of a cross-national survey of exporting firms, the authors present a three-dimensional scale for assessing managerial judgment of short-term export performance (i.e., the STEP scale). The three dimensions are (1) satisfaction with short-term performance improvement, (2) short-term exporting intensity improvement, and (3) expected short-term performance improvement. The scale presents evidence of reliability as well as convergent, discriminant, and nomological validity, and it reveals factorial similarity and factorial equivalence across both samples. The authors outline managerial and public policy implications that stem from the scale and identify avenues for further export marketing research.

Diverse mechanisms underlying the regulation of ion channels by carbon monoxide

Carbon monoxide (CO) is firmly established as an important, physiological signalling molecule as well as a potent toxin. Through its ability to bind metal-containing proteins, it is known to interfere with a number of intracellular signalling pathways, and such actions can account for its physiological and pathological effects. In particular, CO can modulate the intracellular production of reactive oxygen species, NO and cGMP levels, as well as regulate MAPK signalling. In this review, we consider ion channels as more recently discovered effectors of CO signalling. CO is now known to regulate a growing number of different ion channel types, and detailed studies of the underlying mechanisms of action are revealing unexpected findings. For example, there are clear areas of contention surrounding its ability to increase the activity of high conductance, Ca2+ -sensitive K+ channels. More recent studies have revealed the ability of CO to inhibit T-type Ca2+ channels and have unveiled a novel signalling pathway underlying tonic regulation of this channel. It is clear that the investigation of ion channels as effectors of CO signalling is in its infancy, and much more work is required to fully understand both the physiological and the toxic actions of this gas. Only then can its emerging use as a therapeutic tool be fully and safely exploited.

Zombie mouse in a Chinese Room

John Searle’s Chinese Room Argument (CRA) purports to demonstrate that syntax is not sufficient for semantics, and, hence, because computation cannot yield understanding, the computational theory of mind, which equates the mind to an information processing system based on formal computations, fails. In this paper, we use the CRA, and the debate that emerged from it, to develop a philosophical critique of recent advances in robotics and neuroscience. We describe results from a body of work that contributes to blurring the divide between biological and artificial systems; so-called animats, autonomous robots that are controlled by biological neural tissue and what may be described as remote-controlled rodents, living animals endowed with augmented abilities provided by external controllers. We argue that, even though at first sight, these chimeric systems may seem to escape the CRA, on closer analysis, they do not. We conclude by discussing the role of the body–brain dynamics in the processes that give rise to genuine understanding of the world, in line with recent proposals from enactive cognitive science.

Investigating music tempo as a feedback mechanism for closed-loop BCI control

The feedback mechanism used in a brain-computer interface (BCI) forms an integral part of the closed-loop learning process required for successful operation of a BCI. However, ultimate success of the BCI may be dependent upon the modality of the feedback used. This study explores the use of music tempo as a feedback mechanism in BCI and compares it to the more commonly used visual feedback mechanism. Three different feedback modalities are compared for a kinaesthetic motor imagery BCI: visual, auditory via music tempo, and a combined visual and auditory feedback modality. Visual feedback is provided via the position, on the y-axis, of a moving ball. In the music feedback condition, the tempo of a piece of continuously generated music is dynamically adjusted via a novel music-generation method. All the feedback mechanisms allowed users to learn to control the BCI. However, users were not able to maintain as stable control with the music tempo feedback condition as they could in the visual feedback and combined conditions. Additionally, the combined condition exhibited significantly less inter-user variability, suggesting that multi-modal feedback may lead to more robust results. Finally, common spatial patterns are used to identify participant-specific spatial filters for each of the feedback modalities. The mean optimal spatial filter obtained for the music feedback condition is observed to be more diffuse and weaker than the mean spatial filters obtained for the visual and combined feedback conditions.

Neural correlates of emotional responses to music: an EEG study

This paper presents an EEG study into the neural correlates of music-induced emotions. We presented participants with a large dataset containing musical pieces in different styles, and asked them to report on their induced emotional responses. We found neural correlates of music-induced emotion in a number of frequencies over the pre-frontal cortex. Additionally, we found a set of patterns of functional connectivity, defined by inter-channel coherence measures,to be significantly different between groups of music-induced emotional responses.

Investigating affect in algorithmic composition systems

There has been a significant amount of work implementing systems for algorithmic composition with the intention of targeting specific emotional responses in the listener, but a full review of this work is not currently available. This gap creates a shared obstacle to those entering the field. Our aim is thus to give an overview of progress in the area of these affectively driven systems for algorithmic composition. Performative and transformative systems are included and differentiated where appropriate, highlighting the challenges these systems now face if they are to be adapted to, or have already incorporated, some form of affective control. Possible real-time applications for such systems, utilizing affectively driven algorithmic composition and biophysical sensing to monitor and induce affective states in the listener are suggested.

Changes in music tempo entrain movement related brain activity

The neural mechanisms of music listening and appreciation are not yet completely understood. Based on the apparent relationship between the beats per minute (tempo) of music and the desire to move (for example feet tapping) induced while listening to that music it is hypothesised that musical tempo may evoke movement related activity in the brain. Participants are instructed to listen, without moving, to a large range of musical pieces spanning a range of styles and tempos during an electroencephalogram (EEG) experiment. Event-related desynchronisation (ERD) in the EEG is observed to correlate significantly with the variance of the tempo of the musical stimuli. This suggests that the dynamics of the beat of the music may induce movement related brain activity in the motor cortex. Furthermore, significant correlations are observed between EEG activity in the alpha band over the motor cortex and the bandpower of the music in the same frequency band over time. This relationship is observed to correlate with the strength of the ERD, suggesting entrainment of motor cortical activity relates to increased ERD strength

Evaluating perceptual separation in a pilot system for affective composition

Research evaluating perceptual responses to music has identified many structural features as correlates that might be incorporated in computer music systems for affectively charged algorithmic composition and/or expressive music performance. In order to investigate the possible integration of isolated musical features to such a system, a discrete feature known to correlate some with emotional responses – rhythmic density – was selected from a literature review and incorporated into a prototype system. This system produces variation in rhythm density via a transformative process. A stimulus set created using this system was then subjected to a perceptual evaluation. Pairwise comparisons were used to scale differences between 48 stimuli. Listener responses were analysed with Multidimensional scaling (MDS). The 2-Dimensional solution was then rotated to place the stimuli with the largest range of variation across the horizontal plane. Stimuli with variation in rhythmic density were placed further from the source material than stimuli that were generated by random permutation. This, combined with the striking similarity between the MDS scaling and that of the 2-dimensional emotional model used by some affective algorithmic composition systems, suggests that isolated musical feature manipulation can now be used to parametrically control affectively charged automated composition in a larger system.