560 research outputs found
Maladaptive cognitive appraisals in children with high-functioning autism : associations with fear, anxiety and theory of mind
Despite the well-documented success of cognitive restructuring techniques in the treatment of anxiety disorders, there is still little clarity on which cognitions underpin fear and anxiety in children with high-functioning spectrum disorders (HFASD). This study examined whether certain cognitive appraisals, known to be associated with fear and anxiety in non-HFASD groups, may help explain these emotions in children with HFASD. It also investigated relations between these cognitive appraisals and theory-of-mind (TOM). Using a vignette approach, appraisals, fear and anxiety were assessed in 22 children with HFASD and 22 typically developing (TD) children. The two groups differed significantly on all four appraisal types. Anxiety was negatively correlated with future expectancy and positively with problem-focused coping potential in the HFASD group, but was not correlated with appraisals in the TD group. Emotion-focused coping potential was the only appraisal correlated with fear in the HFASD group and only self-accountability in the TD group. Linear regression analysis found appraisals of emotion-focused coping potential, problem-focused coping potential and future expectancy to be significant predictors of TOM ability in the HFASD group. These findings indicate that specific, problematic patterns of appraisal may characterise children with HFASD
Interpretation of heart rate variability via detrended fluctuation analysis and alpha-beta filter
Detrended fluctuation analysis (DFA), suitable for the analysis of
nonstationary time series, has confirmed the existence of persistent long-range
correlations in healthy heart rate variability data. In this paper, we present
the incorporation of the alpha-beta filter to DFA to determine patterns in the
power-law behaviour that can be found in these correlations. Well-known
simulated scenarios and real data involving normal and pathological
circumstances were used to evaluate this process. The results presented here
suggest the existence of evolving patterns, not always following a uniform
power-law behaviour, that cannot be described by scaling exponents estimated
using a linear procedure over two predefined ranges. Instead, the power law is
observed to have a continuous variation with segment length. We also show that
the study of these patterns, avoiding initial assumptions about the nature of
the data, may confer advantages to DFA by revealing more clearly abnormal
physiological conditions detected in congestive heart failure patients related
to the existence of dominant characteristic scales.Comment: 18 pages, 14 figure
CCBuilder:An interactive web-based tool for building, designing and assessing coiled-coil protein assemblies
Motivation: The ability to accurately model protein structures at the atomistic level underpins efforts to understand protein folding, to engineer natural proteins predictably and to design proteins de novo . Homology-based methods are well established and produce impressive results. However, these are limited to structures presented by and resolved for natural proteins. Addressing this problem more widely and deriving truly ab initio models requires mathematical descriptions for protein folds; the means to decorate these with natural, engineered or de novo sequences; and methods to score the resulting models.
Results: We present CCBuilder, a web-based application that tackles the problem for a defined but large class of protein structure, the α-helical coiled coils. CCBuilder generates coiled-coil backbones, builds side chains onto these frameworks and provides a range of metrics to measure the quality of the models. Its straightforward graphical user interface provides broad functionality that allows users to build and assess models, in which helix geometry, coiled-coil architecture and topology and protein sequence can be varied rapidly. We demonstrate the utility of CCBuilder by assembling models for 653 coiled-coil structures from the PDB, which cover >96% of the known coiled-coil types, and by generating models for rarer and de novo coiled-coil structures.
Availability and implementation: CCBuilder is freely available, without registration, at http://coiledcoils.chm.bris.ac.uk/app/cc_builder
Attractiveness of periodic orbits in parametrically forced systemswith time-increasing friction
We consider dissipative one-dimensional systems subject to a periodic force
and study numerically how a time-varying friction affects the dynamics. As a
model system, particularly suited for numerical analysis, we investigate the
driven cubic oscillator in the presence of friction. We find that, if the
damping coefficient increases in time up to a final constant value, then the
basins of attraction of the leading resonances are larger than they would have
been if the coefficient had been fixed at that value since the beginning. From
a quantitative point of view, the scenario depends both on the final value and
the growth rate of the damping coefficient. The relevance of the results for
the spin-orbit model are discussed in some detail.Comment: 30 pages, 6 figure
Modular Design of Self-Assembling Peptide-Based Nanotubes.
An ability to design peptide-based nanotubes (PNTs) rationally with defined and mutable internal channels would advance understanding of peptide self-assembly, and present new biomaterials for nanotechnology and medicine. PNTs have been made from Fmoc dipeptides, cyclic peptides, and lock-washer helical bundles. Here we show that blunt-ended α-helical barrels, that is, preassembled bundles of α-helices with central channels, can be used as building blocks for PNTs. This approach is general and systematic, and uses a set of de novo helical bundles as standards. One of these bundles, a hexameric α-helical barrel, assembles into highly ordered PNTs, for which we have determined a structure by combining cryo-transmission electron microscopy, X-ray fiber diffraction, and model building. The structure reveals that the overall symmetry of the peptide module plays a critical role in ripening and ordering of the supramolecular assembly. PNTs based on pentameric, hexameric, and heptameric α-helical barrels sequester hydrophobic dye within their lumens.N.C.B. thanks the EPSRC-funded Bristol Centre for Functional Nanomaterials Centre for Doctoral Training for a postgraduate scholarship (EP/G036780/1). F.T. and D.N.W. thank the Leverhulme Trust for funding (RPG-2012-536). D.N.W. holds a Royal Society Wolfson Research Merit Award.This is the author accepted manuscript. The final version is available from the American Chemical Society via http://dx.doi.org/10.1021/jacs.5b0397
A monodisperse transmembrane α-helical peptide barrel
The fabrication of monodisperse transmembrane barrels formed from short synthetic peptides has not been demonstrated previously. This is in part because of the complexity of the interactions between peptides and lipids within the hydrophobic environment of a membrane. Here we report the formation of a transmembrane pore through the self-assembly of 35 amino acid α-helical peptides. The design of the peptides is based on the C-terminal D4 domain of the Escherichia coli polysaccharide transporter Wza. By using single-channel current recording, we define discrete assembly intermediates and show that the pore is most probably a helix barrel that contains eight D4 peptides arranged in parallel. We also show that the peptide pore is functional and capable of conducting ions and binding blockers. Such α-helix barrels engineered from peptides could find applications in nanopore technologies such as single-molecule sensing and nucleic-acid sequencing
Microlaser-based contractility sensing in single cardiomyocytes and whole hearts
Microscopic whispering gallery mode lasers detect minute changes in cellular refractive index inside individual cardiac cells and in live zebrafish. We show that these signals encode cardiac contractility that can be used for intravital sensing.Postprin
Toward a soluble model system for the amyloid state
The formation and
deposition of amyloids is associated with many
diseases. ÎČ-Sheet secondary structure is a common feature of
amyloids, but the packing of sheets against one another is distinctive
relative to soluble proteins. Standard methods that rely on perturbing
a polypeptideâs sequence and evaluating impact on folding can
be problematic for amyloid aggregates because a single sequence can
adopt multiple conformations and diverse packing arrangements. We
describe initial steps toward a minimum-sized, soluble model system
for the amyloid state that supports comparisons among sequence variants.
Critical to this goal is development of a new linking strategy to
enable intersheet association mediated by side chain interactions,
which is characteristic of the amyloid state. The linker design we
identified should ultimately support exploration of relationships
between sequence and amyloid state stability for specific strand-association
modes
Clinical utilisation of implantable loop recorders in adults with Fabry disease-a multi-centre snapshot study
Fabry disease (FD) is an X-linked deficiency of alpha-galactosidase-A, leading to lysosomal storage of sphingolipids in multiple organs. Myocardial accumulation contributes to arrhythmia and sudden death, the most common cause of FD mortality. Therefore, there is a need for risk stratification and prediction to target device therapy. Implantable loop recorders (ILRs) allow for continual rhythm monitoring for up to 3 years. Here, we performed a retrospective study to evaluate current ILR utilisation in FD and quantify the burden of arrhythmia that was detected, which resulted in a modification of therapy. This was a snapshot assessment of 915 patients with FD across three specialist centres in England during the period between 1 January 2000 and 1 September 2022. In total, 22 (2.4%) patients underwent clinically indicated ILR implantation. The mean implantation age was 50 years and 13 (59%) patients were female. Following implantation, nine (41%) patients underwent arrhythmia detection, requiring intervention (six on ILR and three post-ILR battery depletion). Three patients experienced sustained atrial high-rate episodes and were started on anticoagulation. Three had non-sustained tachyarrhythmia and were started on beta blockers. Post-ILR battery depletion, one suffered complete heart block and two had sustained ventricular tachycardia, all requiring device therapy. Those with arrhythmia had a shorter PR interval on electrocardiography. This study demonstrates that ILR implantation in FD uncovers a high burden of arrhythmia. ILRs are likely to be underutilised in this pro-arrhythmic cohort, perhaps restricted to those with advanced FD cardiomyopathy. Following battery depletion in three patients as mentioned above, greater vigilance and arrhythmia surveillance are advised for those experiencing major arrhythmic events post-ILR monitoring. Further work is required to establish who would benefit most from implantation.</p
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