Heart rate variability is associated with amygdala functional connectivity with MPFC across younger and older adults

The ability to regulate emotion is crucial to promote well-being. Evidence suggests that the medial prefrontal cortex (mPFC) and adjacent anterior cingulate (ACC) modulate amygdala activity during emotion regulation. Yet less is known about whether the amygdala-mPFC circuit is linked with regulation of the autonomic nervous system and whether the relationship differs across the adult lifespan. The current study tested the hypothesis that heart rate variability (HRV) reflects the strength of mPFC-amygdala interaction across younger and older adults. We recorded participants’ heart rates at baseline and examined whether baseline HRV was associated with amygdala-mPFC functional connectivity during rest. We found that higher HRV was associated with stronger functional connectivity between the amygdala and the mPFC during rest across younger and older adults. In addition to this age-invariant pattern, there was an age-related change, such that greater HRV was linked with stronger functional connectivity between amygdala and ventrolateral PFC (vlPFC) in younger than in older adults. These results are in line with past evidence that vlPFC is involved in emotion regulation especially in younger adults. Taken together, our results support the neurovisceral integration model and suggest that higher heart rate variability is associated with neural mechanisms that support successful emotional regulation across the adult lifespan.

Blind equalization of nonminimum phase channels: higher order cumulant based algorithm

Higher order cumulant analysis is applied to the blind equalization of linear time-invariant (LTI) nonminimum-phase channels. The channel model is moving-average based. To identify the moving average parameters of channels, a higher-order cumulant fitting approach is adopted in which a novel relay algorithm is proposed to obtain the global solution. In addition, the technique incorporates model order determination. The transmitted data are considered as independently identically distributed random variables over some discrete finite set (e.g., set {±1, ±3}). A transformation scheme is suggested so that third-order cumulant analysis can be applied to this type of data. Simulation examples verify the feasibility and potential of the algorithm. Performance is compared with that of the noncumulant-based Sato scheme in terms of the steady state MSE and convergence rate.

Reduced heart rate responding to trauma reliving in trauma survivors with PTSD: correlates and consequences

The authors investigated whether heart rate (HR) responses to voluntary recall of trauma memories (a) are related to posttraumatic stress disorder (PTSD), and (b) predict recovery 6 months later. Sixty-two assault survivors completed a recall task modeled on imaginal reliving in the initial weeks postassault. Possible cognitive modulators of HR responsivity were assessed; dissociation, rumination, trauma memory disorganization. Individuals with PTSD showed a reduced HR response to reliving compared to those without PTSD, but reported greater distress. Notably, higher HR response but not self-reported distress during reliving predicted greater symptom reduction at follow-up in participants with PTSD. Engagement in rumination was the only cognitive factor that predicted lower HR response. The data are in contrast to studies using trauma reminders to trigger memories, which have found greater physiological reactivity in PTSD. The authors' observations are consistent with models of PTSD that highlight differences between cued or stimulus-driven retrieval and intentional trauma recall, and with E B. Foa and M.J. Kozak (1986) hypothesis that full activation of trauma memories facilitates emotional processing.

Structural characterisation of bisintercalation in higher-order DNA at a junction-like quadruplex

We report the single-crystal X-ray structure for the complex of the bisacridine bis-(9-aminooctyl(2-(dimethylaminoethyl)acridine-4-carboxamide)) with the oligonucleotide d(CGTACG)2 to a resolution of 2.4 Å. Solution studies with closed circular DNA show this compound to be a bisintercalating threading agent, but so far we have no crystallographic or NMR structural data conforming to the model of contiguous intercalation within the same duplex. Here, with the hexameric duplex d(CGTACG), the DNA is observed to undergo a terminal cytosine base exchange to yield an unusual guanine quadruplex intercalation site through which the bisacridine threads its octamethylene linker to fuse two DNA duplexes. The 4-carboxamide side-chains form anchoring hydrogen-bonding interactions with guanine O6 atoms on each side of the quadruplex. This higher-order DNA structure provides insight into an unexpected property of bisintercalating threading agents, and suggests the idea of targeting such compounds specifically at four-way DNA junctions.

Quantitative single-molecule localization microscopy combined with rule-based modeling reveals ligand-induced TNF-R1 reorganization toward higher-order oligomers

We report on the assembly of tumor necrosis factor receptor 1 (TNF-R1) prior to ligand activation and its ligand-induced reorganization at the cell membrane. We apply single-molecule localization microscopy to obtain quantitative information on receptor cluster sizes and copy numbers. Our data suggest a dimeric pre-assembly of TNF-R1, as well as receptor reorganization toward higher oligomeric states with stable populations comprising three to six TNF-R1. Our experimental results directly serve as input parameters for computational modeling of the ligand-receptor interaction. Simulations corroborate the experimental finding of higher-order oligomeric states. This work is a first demonstration how quantitative, super-resolution and advanced microscopy can be used for systems biology approaches at the single-molecule and single-cell level.

A phylogenetic mixture model for detecting pattern-heterogeneity in gene sequence or character-state data

We describe a general likelihood-based 'mixture model' for inferring phylogenetic trees from gene-sequence or other character-state data. The model accommodates cases in which different sites in the alignment evolve in qualitatively distinct ways, but does not require prior knowledge of these patterns or partitioning of the data. We call this qualitative variability in the pattern of evolution across sites "pattern-heterogeneity" to distinguish it from both a homogenous process of evolution and from one characterized principally by differences in rates of evolution. We present studies to show that the model correctly retrieves the signals of pattern-heterogeneity from simulated gene-sequence data, and we apply the method to protein-coding genes and to a ribosomal 12S data set. The mixture model outperforms conventional partitioning in both these data sets. We implement the mixture model such that it can simultaneously detect rate- and pattern-heterogeneity. The model simplifies to a homogeneous model or a rate- variability model as special cases, and therefore always performs at least as well as these two approaches, and often considerably improves upon them. We make the model available within a Bayesian Markov-chain Monte Carlo framework for phylogenetic inference, as an easy-to-use computer program.

A continuum anisotropic model of sea-ice dynamics

We develop the essential ingredients of a new, continuum and anisotropic model of sea-ice dynamics designed for eventual use in climate simulation. These ingredients are a constitutive law for sea-ice stress, relating stress to the material properties of sea ice and to internal variables describing the sea-ice state, and equations describing the evolution of these variables. The sea-ice cover is treated as a densely flawed two-dimensional continuum consisting of a uniform field of thick ice that is uniformly permeated with narrow linear regions of thinner ice called leads. Lead orientation, thickness and width distributions are described by second-rank tensor internal variables: the structure, thickness and width tensors, whose dynamics are governed by corresponding evolution equations accounting for processes such as new lead generation and rotation as the ice cover deforms. These evolution equations contain contractions of higher-order tensor expressions that require closures. We develop a sea-ice stress constitutive law that relates sea-ice stress to the structure tensor, thickness tensor and strain rate. For the special case of empty leads (containing no ice), linear closures are adopted and we present calculations for simple shear, convergence and divergence.

Hidden Markov analysis describes dive patterns in semiaquatic animals

Existing methods of dive analysis, developed for fully aquatic animals, tend to focus on frequency of behaviors rather than transitions between them. They, therefore, do not account for the variability of behavior of semiaquatic animals, and the switching between terrestrial and aquatic environments. This is the first study to use hidden Markov models (HMM) to divide dives of a semiaquatic animal into clusters and thus identify the environmental predictors of transition between behavioral modes. We used 18 existing data sets of the dives of 14 American mink (Neovison vison) fitted with time-depth recorders in lowland England. Using HMM, we identified 3 behavioral states (1, temporal cluster of dives; 2, more loosely aggregated diving within aquatic activity; and 3, terminal dive of a cluster or a single, isolated dive). Based on the higher than expected proportion of dives in State 1, we conclude that mink tend to dive in clusters. We found no relationship between temperature and the proportion of dives in each state or between temperature and the rate of transition between states, meaning that in our study area, mink are apparently not adopting different diving strategies at different temperatures. Transition analysis between states has shown that there is no correlation between ambient temperature and the likelihood of mink switching from one state to another, that is, changing foraging modes. The variables provided good discrimination and grouped into consistent states well, indicating promise for further application of HMM and other state transition analyses in studies of semiaquatic animals.

Autonomic arousal in childhood anxiety disorders: associations with state anxiety and social anxiety disorder

Background Psychophysiological theories suggest that individuals with anxiety disorders may evidence inflexibility in their autonomic activity at rest and when responding to stressors. In addition, theories of social anxiety disorder, in particular, highlight the importance of physical symptoms. Research on autonomic activity in childhood (social) anxiety disorders, however, is scarce and has produced inconsistent findings, possibly because of methodological limitations. Method The present study aimed to account for limitations of previous studies and measured respiratory sinus arrhythmia (RSA) and heart rate (HR) using Actiheart heart rate monitors and software (Version 4) during rest and in response to a social and a non-social stressor in 60 anxious (30 socially anxious and 30 ‘other’ anxious), and 30 nonanxious sex-and age-matched 7–12 year olds. In addition, the effect of state anxiety during the tasks was explored. Results No group differences at rest or in response to stress were found. Importantly, however, with increases in state anxiety, all children, regardless of their anxiety diagnoses showed less autonomic responding (i.e., less change in HR and RSA from baseline in response to task) and took longer to recover once the stressor had passed. Limitations This study focused primarily on parasympathetic arousal and lacked measures of sympathetic arousal. Conclusion The findings suggest that childhood anxiety disorders may not be characterized by inflexible autonomic responding, and that previous findings to the contrary may have been the result of differences in subjective anxiety between anxious and nonanxious groups during the tasks, rather than a function of chronic autonomic dysregulation.

Activation of c-Jun N-terminal kinases and p38-mitogen-activated protein kinases in human heart failure secondary to ischaemic heart disease.

Three well-characterized mitogen-activated protein kinase (MAPK) subfamilies are expressed in rodent and rabbit hearts, and are activated by pathophysiological stimuli. We have determined and compared the expression and activation of these MAPKs in donor and failing human hearts. The amount and activation of MAPKs was assessed in samples from the left ventricles of 4 unused donor hearts and 12 explanted hearts from patients with heart failure secondary to ischaemic heart disease. Total MAPKs or dually phosphorylated (activated) MAPKs were detected by Western blotting and MAPK activities were measured by in gel kinase assays. As in rat heart, c-Jun N-terminal kinases (JNKs) were detected in human hearts as bands corresponding to 46 and 54 kDa; p38-MAPK(s) was detected as a band corresponding to approximately 40 kDa, and extracellularly regulated kinases, ERK1 and ERK2, were detected as 44- and 42-kDa bands respectively. The total amounts of 54 kDa JNK, p38-MAPK and ERK2 were similar in all samples, although 46-kDa JNK was reduced in the failing hearts. However, the mean activities of JNKs and p38-MAPK(s) were significantly higher in failing heart samples than in those from donor hearts (P<0.05). There was no significant difference in phosphorylated (activated) ERKs between the two groups. In conclusion, JNKs, p38-MAPK(s) and ERKs are expressed in the human heart and the activities of JNKs and p38-MAPK(s) were increased in heart failure secondary to ischaemic heart disease. These data indicate that JNKs and p38-MAPKs may be important in human cardiac pathology.