Study protocol: evaluation of a parenting and stress management programme: a randomised controlled trial of Triple P discussion groups and stress control

<br>Background: Children displaying psychosocial problems are at an increased risk of negative developmental outcomes. Parenting practices are closely linked with child development and behaviour, and parenting programmes have been recommended in the treatment of child psychosocial problems. However, parental mental health also needs to be addressed when delivering parenting programmes as it is linked with parenting practices, child outcomes, and treatment outcomes of parenting programmes. This paper describes the protocol of a study examining the effects of a combined intervention of a parenting programme and a cognitive behavioural intervention for mental health problems.</br> <br>Methods: The effects of a combined intervention of Triple P Discussion Groups and Stress Control will be examined using a randomised controlled trial design. Parents with a child aged 3?8?years will be recruited to take part in the study. After obtaining informed consent and pre-intervention measures, participants will be randomly assigned to either an intervention or a waitlist condition. The two primary outcomes for this study are change in dysfunctional/ineffective parenting practices and change in symptoms of depression, anxiety, and stress. Secondary outcomes are child behaviour problems, parenting experiences, parental self-efficacy, family relationships, and positive parental mental health. Demographic information, participant satisfaction with the intervention, and treatment fidelity data will also be collected. Data will be collected at pre-intervention, mid-intervention, post-intervention, and 3-month follow-up.</br> <br>Discussion: The aim of this paper is to describe the study protocol of a randomised controlled trial evaluating the effects of a combined intervention of Triple P Discussion Groups and Stress Control in comparison to a waitlist condition. This study is important because it will provide evidence about the effects of this combined intervention for parents with 3?8?year old children. The results of the study could be used to inform policy about parenting support and support for parents with mental health problems. Trial registration ClinicalTrial.gov: NCT01777724, UTN: U1111-1137-1053.</br&gt

Ageing memory and glassiness of a driven vortex system

Many systems in nature, glasses, interfaces and fractures being some examples, cannot equilibrate with their environment, which gives rise to novel and surprising behaviour such as memory effects, ageing and nonlinear dynamics. Unlike their equilibrated counterparts, the dynamics of out-of- equilibrium systems is generally too complex to be captured by simple macroscopic laws. Here we investigate a system that straddles the boundary between glass and crystal: a Bragg glass formed by vortices in a superconductor. We find that the response to an applied force evolves according to a stretched exponential, with the exponent reflecting the deviation from equilibrium. After the force is removed, the system ages with time and its subsequent response time scales linearly with its age (simple ageing), meaning that older systems are slower than younger ones. We show that simple ageing can occur naturally in the presence of sufficient quenched disorder. Moreover, the hierarchical distribution of timescales, arising when chunks of loose vortices cannot move before trapped ones become dislodged, leads to a stretched-exponential response.Comment: 16 pages, 5 figure

Topological dissection of the membrane transport protein Mhp1 derived from cysteine accessibility and mass spectrometry

Cys accessibility and quantitative intact mass spectrometry (MS) analyses have been devised to study the topological transitions of Mhp1, the membrane protein for sodium-linked transport of hydantoins from Microbacterium liquefaciens. Mhp1 has been crystallised in three forms (outward-facing open, outward-facing occluded with substrate bound, and inward-facing open). We show that one natural cysteine residue, Cys327, out of three, has an enhanced solvent accessibility in the inward-facing (relative to the outward-facing) form. Reaction of the purified protein, in detergent, with the thiol-reactive N-ethylmalemide (NEM), results in modification of Cys327, suggesting that Mhp1 adopts predominantly inward-facing conformations. Addition of either sodium ions or the substrate 5-benzyl-L-hydantoin (L-BH) does not shift this conformational equilibrium, but, systematic co-addition of the two results in an attenuation of labelling, indicating a shift toward outward-facing conformations that can be interpreted using conventional enzyme kinetic analyses. Such measurements can afford the Km for each ligand as well as the stoichiometry of ion-substrate coupled conformational changes. Mutations that perturb the substrate binding site either result in the protein being unable to adopt outward-facing conformations or in a global destabilisation of structure. The methodology combines covalent labeling, mass spectrometry and kinetic analyses in a straightforward workflow applicable to a range of systems, enabling the interrogation of changes in a protein’s conformation required for function at varied concentrations of substrates, and the consequences of mutations on these conformational transitions

Quantum correlations and synchronization measures

The phenomenon of spontaneous synchronization is universal and only recently advances have been made in the quantum domain. Being synchronization a kind of temporal correlation among systems, it is interesting to understand its connection with other measures of quantum correlations. We review here what is known in the field, putting emphasis on measures and indicators of synchronization which have been proposed in the literature, and comparing their validity for different dynamical systems, highlighting when they give similar insights and when they seem to fail.Comment: book chapter, 18 pages, 7 figures, Fanchini F., Soares Pinto D., Adesso G. (eds) Lectures on General Quantum Correlations and their Applications. Quantum Science and Technology. Springer (2017

Six weeks' sebacic acid supplementation improves fasting plasma glucose, HbA1c and glucose tolerance in db/db mice

Aim: To investigate the impact of chronic ingestion of sebacic acid (SA), a 10-carbon medium-chain dicarboxylic acid, on glycaemic control in a mouse model of type 2 diabetes (T2D)

Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex

The PAF complex (PAFC) coordinates transcription elongation and mRNA processing and its CDC73/parafibromin subunit functions as a tumour suppressor. The NF2/Merlin tumour suppressor functions both at the cell cortex and nucleus and is a key mediator of contact inhibition but the molecular mechanisms remain unclear. In this study we have used affinity proteomics to identify novel Merlin interacting proteins and show that Merlin forms a complex with multiple proteins involved in RNA processing including the PAFC and the CHD1 chromatin remodeller. Tumour-derived inactivating mutations in both Merlin and the CDC73 PAFC subunit mutually disrupt their interaction and growth suppression by Merlin requires CDC73. Merlin interacts with the PAFC in a cell density-dependent manner and we identify a role for FAT cadherins in regulating the Merlin-PAFC interaction. Our results suggest that in addition to its function within the Hippo pathway, Merlin is part of a tumour suppressor network regulated by cell-cell adhesion which coordinates post-initiation steps of the transcription cycle of genes mediating contact inhibition

Phenotypic Variation and Bistable Switching in Bacteria

Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.

Looking to Score: The Dissociation of Goal Influence on Eye Movement and Meta-Attentional Allocation in a Complex Dynamic Natural Scene

Several studies have reported that task instructions influence eye-movement behavior during static image observation. In contrast, during dynamic scene observation we show that while the specificity of the goal of a task influences observers’ beliefs about where they look, the goal does not in turn influence eye-movement patterns. In our study observers watched short video clips of a single tennis match and were asked to make subjective judgments about the allocation of visual attention to the items presented in the clip (e.g., ball, players, court lines, and umpire). However, before attending to the clips, observers were either told to simply watch clips (non-specific goal), or they were told to watch the clips with a view to judging which of the two tennis players was awarded the point (specific goal). The results of subjective reports suggest that observers believed that they allocated their attention more to goal-related items (e.g. court lines) if they performed the goal-specific task. However, we did not find the effect of goal specificity on major eye-movement parameters (i.e., saccadic amplitudes, inter-saccadic intervals, and gaze coherence). We conclude that the specificity of a task goal can alter observer’s beliefs about their attention allocation strategy, but such task-driven meta-attentional modulation does not necessarily correlate with eye-movement behavior

SVOP Is a Nucleotide Binding Protein

Background: Synaptic Vesicle Protein 2 (SV2) and SV2-related protein (SVOP) are transporter-like proteins that localize to neurotransmitter-containing vesicles. Both proteins share structural similarity with the major facilitator (MF) family of small molecule transporters. We recently reported that SV2 binds nucleotides, a feature that has also been reported for another MF family member, the human glucose transporter 1 (Glut1). In the case of Glut1, nucleotide binding affects transport activity. In this study, we determined if SVOP also binds nucleotides and assessed its nucleotide binding properties. Methodology/Principal Findings: We performed in vitro photoaffinity labeling experiments with the photoreactive ATP analogue, 8-azido-ATP[c] biotin and purified recombinant SVOP-FLAG fusion protein. We found that SVOP is a nucleotide-binding protein, although both its substrate specificity and binding site differ from that of SV2. Within the nucleotides tested, ATP, GTP and NAD show same level of inhibition on SVOP-FLAG labeling. Dose dependent studies indicated that SVOP demonstrates the highest affinity for NAD, in contrast to SV2, which binds both NAD and ATP with equal affinity. Mapping of the binding site revealed a single region spanning transmembrane domains 9–12, which contrasts to the two binding sites in the large cytoplasmic domains in SV2A. Conclusions/Significance: SVOP is the third MF family member to be found to bind nucleotides. Given that the binding sites are unique in SVOP, SV2 and Glut1, this feature appears to have arisen separately

Nucleocytoplasmic transport: a thermodynamic mechanism

The nuclear pore supports molecular communication between cytoplasm and nucleus in eukaryotic cells. Selective transport of proteins is mediated by soluble receptors, whose regulation by the small GTPase Ran leads to cargo accumulation in, or depletion from the nucleus, i.e., nuclear import or nuclear export. We consider the operation of this transport system by a combined analytical and experimental approach. Provocative predictions of a simple model were tested using cell-free nuclei reconstituted in Xenopus egg extract, a system well suited to quantitative studies. We found that accumulation capacity is limited, so that introduction of one import cargo leads to egress of another. Clearly, the pore per se does not determine transport directionality. Moreover, different cargo reach a similar ratio of nuclear to cytoplasmic concentration in steady-state. The model shows that this ratio should in fact be independent of the receptor-cargo affinity, though kinetics may be strongly influenced. Numerical conservation of the system components highlights a conflict between the observations and the popular concept of transport cycles. We suggest that chemical partitioning provides a framework to understand the capacity to generate concentration gradients by equilibration of the receptor-cargo intermediary.Comment: in press at HFSP Journal, vol 3 16 text pages, 1 table, 4 figures, plus Supplementary Material include