Amygdalar function reflects common individual differences in emotion and pain regulation success

Although the co-occurrence of negative affect and pain is well recognized, the mechanism underlying their association is unclear. To examine whether a common self-regulatory ability impacts the experience of both emotion and pain, we integrated neuroimaging, behavioral, and physiological measures obtained from three assessments separated by substantial temporal intervals. Out results demonstrated that individual differences in emotion regulation ability, as indexed by an objective measure of emotional state, corrugator electromyography, predicted self-reported success while regulating pain. In both emotion and pain paradigms, the amygdala reflected regulatory success. Notably, we found that greater emotion regulation success was associated with greater change of amygdalar activity following pain regulation. Furthermore, individual differences in degree of amygdalar change following emotion regulation were a strong predictor of pain regulation success, as well as of the degree of amygdalar engagement following pain regulation. These findings suggest that common individual differences in emotion and pain regulatory success are reflected in a neural structure known to contribute to appraisal processes.

Emotion processing in infancy: specificity in risk for social anxiety and associations with two year outcomes

The current study examined the specificity of patterns of responding to high and low intensity negative emotional expressions of infants of mothers with social phobia, and their association with child outcomes at two years of age. Infants of mothers with social phobia, generalised anxiety disorder (GAD) or no history of anxiety were shown pairs of angry and fearful emotional expressions at 10 weeks of age. Symptoms of social withdrawal, anxiety and sleep problems were assessed at two years of age. Only infants of mothers with social phobia showed a tendency to look away from high intensity fear faces; however infants of mothers with both social phobia and GAD showed a bias towards high intensity angry faces. Among the offspring of mothers with social phobia, anxiety symptoms at two years of age were associated with a preference for high intensity fear faces in infancy. The reverse pattern was found amongst the offspring of non-anxious mothers. These findings suggest a possible specific response to emotional expressions among the children of mothers with social phobia.

Conformational modulation of sequence recognition in synthetic macromolecules

The different triplet sequences in high molecular weight aromatic copolyimides comprising pyromellitimide units ("I") flanked by either ether-ketone ("K") or ether-sulfone residues ("S") show different binding strengths for pyrene-based tweezer-molecules. Such molecules bind primarily to the diimide unit through complementary π-π-stacking and hydrogen bonding. However, as shown by the magnitudes of 1H NMR complexation shifts and tweezer-polymer binding constants, the triplet "SIS" binds tweezer-molecules more strongly than "KIS" which in turn bind such molecules more strongly than "KIK". Computational models for tweezer-polymer binding, together with single-crystal X-ray analyses of tweezer-complexes with macrocyclic ether-imides, reveal that the variations in binding strength between the different triplet sequences arise from the different conformational preferences of aromatic rings at diarylketone and diarylsulfone linkages. These preferences determine whether or not chain-folding and secondary π−π-stacking occurs between the arms of the tweezermolecule and the 4,4'-biphenylene units which flank the central diimide residue.

The longitudinal development of emotion regulation capacities in children at risk for externalizing disorders

The development of emotional regulation capacities in children at high versus low risk for externalizing disorder was examined in a longitudinal study investigating: a) whether disturbances in emotion regulation precede and predict the emergence of externalizing symptoms; and b) whether sensitive maternal behavior is a significant influence on the development of child emotion regulation. Families experiencing high (n=58) and low (n=63) levels of psychosocial adversity were recruited to the study during pregnancy. Direct observational assessments of child emotion regulation capacities and maternal sensitivity were completed in early infancy, at 12 and 18-months, and at 5-years. Key findings were as follows. First, high risk children showed poorer emotion regulation capacities than their low risk counterparts at every stage of assessment. Second, from 12-months onwards, emotion regulation capacities showed a degree of stability, and were associated with behavioral problems, both concurrently and prospectively. Third, maternal sensitivity was related to child emotion regulation capacities throughout development, with poorer emotion regulation in the high risk group being associated with lower maternal sensitivity. The results are consistent with a causal role for problems in the regulation of negative emotions in the etiology of externalizing psychopathology, and highlight insensitive parenting as a potentially key developmental influence.

Spoken word recognition in adolescents with autism spectrum disorders and specific language impairment

Spoken word recognition, during gating, appears intact in specific language impairment (SLI). This study used gating to investigate the process in adolescents with autism spectrum disorders plus language impairment (ALI). Adolescents with ALI, SLI, and typical language development (TLD), matched on nonverbal IQ listened to gated words that varied in frequency (low/high) and number of phonological onset neighbors (low/high density). Adolescents with ALI required more speech input to initially identify low-frequency words with low competitor density than those with SLI and those with TLD, who did not differ. These differences may be due to less well specified word form representations in ALI.

Improving sequence-based fold recognition by using 3D model quality assessment

Motivation: The ability of a simple method (MODCHECK) to determine the sequence–structure compatibility of a set of structural models generated by fold recognition is tested in a thorough benchmark analysis. Four Model Quality Assessment Programs (MQAPs) were tested on 188 targets from the latest LiveBench-9 automated structure evaluation experiment. We systematically test and evaluate whether the MQAP methods can successfully detect native-likemodels. Results: We show that compared with the other three methods tested MODCHECK is the most reliable method for consistently performing the best top model selection and for ranking the models. In addition, we show that the choice of model similarity score used to assess a model's similarity to the experimental structure can influence the overall performance of these tools. Although these MQAP methods fail to improve the model selection performance for methods that already incorporate protein three dimension (3D) structural information, an improvement is observed for methods that are purely sequence-based, including the best profile–profile methods. This suggests that even the best sequence-based fold recognition methods can still be improved by taking into account the 3D structural information.

Prediction of novel and analogous folds using fragment assembly and fold recognition

A number of new and newly improved methods for predicting protein structure developed by the Jones–University College London group were used to make predictions for the CASP6 experiment. Structures were predicted with a combination of fold recognition methods (mGenTHREADER, nFOLD, and THREADER) and a substantially enhanced version of FRAGFOLD, our fragment assembly method. Attempts at automatic domain parsing were made using DomPred and DomSSEA, which are based on a secondary structure parsing algorithm and additionally for DomPred, a simple local sequence alignment scoring function. Disorder prediction was carried out using a new SVM-based version of DISOPRED. Attempts were also made at domain docking and “microdomain” folding in order to build complete chain models for some targets.

Improvement of the GenTHREADER method for genomic fold recognition

Motivation: In order to enhance genome annotation, the fully automatic fold recognition method GenTHREADER has been improved and benchmarked. The previous version of GenTHREADER consisted of a simple neural network which was trained to combine sequence alignment score, length information and energy potentials derived from threading into a single score representing the relationship between two proteins, as designated by CATH. The improved version incorporates PSI-BLAST searches, which have been jumpstarted with structural alignment profiles from FSSP, and now also makes use of PSIPRED predicted secondary structure and bi-directional scoring in order to calculate the final alignment score. Pairwise potentials and solvation potentials are calculated from the given sequence alignment which are then used as inputs to a multi-layer, feed-forward neural network, along with the alignment score, alignment length and sequence length. The neural network has also been expanded to accommodate the secondary structure element alignment (SSEA) score as an extra input and it is now trained to learn the FSSP Z-score as a measurement of similarity between two proteins. Results: The improvements made to GenTHREADER increase the number of remote homologues that can be detected with a low error rate, implying higher reliability of score, whilst also increasing the quality of the models produced. We find that up to five times as many true positives can be detected with low error rate per query. Total MaxSub score is doubled at low false positive rates using the improved method.

Benchmarking secondary structure prediction for fold recognition

If secondary structure predictions are to be incorporated into fold recognition methods, an assessment of the effect of specific types of errors in predicted secondary structures on the sensitivity of fold recognition should be carried out. Here, we present a systematic comparison of different secondary structure prediction methods by measuring frequencies of specific types of error. We carry out an evaluation of the effect of specific types of error on secondary structure element alignment (SSEA), a baseline fold recognition method. The results of this evaluation indicate that missing out whole helix or strand elements, or predicting the wrong type of element, is more detrimental than predicting the wrong lengths of elements or overpredicting helix or strand. We also suggest that SSEA scoring is an effective method for assessing accuracy of secondary structure prediction and perhaps may also provide a more appropriate assessment of the “usefulness” and quality of predicted secondary structure, if secondary structure alignments are to be used in fold recognition.

What are the baselines for protein fold recognition?

What constitutes a baseline level of success for protein fold recognition methods? As fold recognition benchmarks are often presented without any thought to the results that might be expected from a purely random set of predictions, an analysis of fold recognition baselines is long overdue. Given varying amounts of basic information about a protein—ranging from the length of the sequence to a knowledge of its secondary structure—to what extent can the fold be determined by intelligent guesswork? Can simple methods that make use of secondary structure information assign folds more accurately than purely random methods and could these methods be used to construct viable hierarchical classifications?

Conscientiousness predicts greater recovery from negative emotion

Greater levels of conscientiousness have been associated with lower levels of negative affect. We focus on one mechanism through which conscientiousness may decrease negative affect: effective emotion regulation, as reflected by greater recovery from negative stimuli. In 273 adults who were 35 - 85 years old, we collected self-report measures of personality including conscientiousness and its self-control facet, followed on average 2 years later by psychophysiological measures of emotional reactivity and recovery. Among middle-aged adults (35 - 65 years old), the measures of conscientiousness and self-control predicted greater recovery from, but not reactivity to, negative emotional stimuli. The effect of conscientiousness and self-control on recovery was not driven by other personality variables or by greater task adherence on the part of high conscientiousness individuals. In addition, the effect was specific to negative emotional stimuli and did not hold for neutral or positive emotional stimuli.

How reward modulates mimicry: EMG evidence of greater automatic facial mimicry of more rewarding faces

Spontaneous mimicry is a marker of empathy. Conditions characterized by reduced spontaneous mimicry (e.g., autism) also display deficits in sensitivity to social rewards. We tested if spontaneous mimicry of socially rewarding stimuli (happy faces) depends on the reward value of stimuli in 32 typical participants. An evaluative conditioning paradigm was used to associate different reward values with neutral target faces. Subsequently, electromyographic activity over the Zygomaticus Major was measured whilst participants watched video clips of the faces making happy expressions. Higher Zygomaticus Major activity was found in response to happy faces conditioned with high reward versus low reward. Moreover, autistic traits in the general population modulated the extent of spontaneous mimicry of happy faces. This suggests a link between reward and spontaneous mimicry and provides a possible underlying mechanism for the reduced response to social rewards seen in autism.