1,724 research outputs found

    Myelination induces axonal hotspots of synaptic vesicle fusion that promote sheath growth

    Get PDF
    Myelination of axons by oligodendrocytes enables fast saltatory conduction. Oligodendrocytes are responsive to neuronal activity, which has been shown to induce changes to myelin sheaths, potentially to optimize conduction and neural circuit function. However, the cellular bases of activity-regulated myelination in vivo are unclear, partly due to the difficulty of analyzing individual myelinated axons over time. Activity-regulated myelination occurs in specific neuronal subtypes and can be mediated by synaptic vesicle fusion, but several questions remain: it is unclear whether vesicular fusion occurs stochastically along axons or in discrete hotspots during myelination and whether vesicular fusion regulates myelin targeting, formation, and/or growth. It is also unclear why some neurons, but not others, exhibit activity-regulated myelination. Here, we imaged synaptic vesicle fusion in individual neurons in living zebrafish and documented robust vesicular fusion along axons during myelination. Surprisingly, we found that axonal vesicular fusion increased upon and required myelination. We found that axonal vesicular fusion was enriched in hotspots, namely the heminodal non-myelinated domains into which sheaths grew. Blocking vesicular fusion reduced the stable formation and growth of myelin sheaths, and chemogenetically stimulating neuronal activity promoted sheath growth. Finally, we observed high levels of axonal vesicular fusion only in neuronal subtypes that exhibit activity-regulated myelination. Our results identify a novel "feedforward" mechanism whereby the process of myelination promotes the neuronal activity-regulated signal, vesicular fusion that, in turn, consolidates sheath growth along specific axons selected for myelination

    Self-repair ability of evolved self-assembling systems in cellular automata

    Get PDF
    Self-repairing systems are those that are able to reconfigure themselves following disruptions to bring them back into a defined normal state. In this paper we explore the self-repair ability of some cellular automata-like systems, which differ from classical cellular automata by the introduction of a local diffusion process inspired by chemical signalling processes in biological development. The update rules in these systems are evolved using genetic programming to self-assemble towards a target pattern. In particular, we demonstrate that once the update rules have been evolved for self-assembly, many of those update rules also provide a self-repair ability without any additional evolutionary process aimed specifically at self-repair

    Wavelength-scale stationary-wave integrated Fourier-transform spectrometry

    Get PDF
    Spectrometry is a general physical-analysis approach for investigating light-matter interactions. However, the complex designs of existing spectrometers render them resistant to simplification and miniaturization, both of which are vital for applications in micro- and nanotechnology and which are now undergoing intensive research. Stationary-wave integrated Fourier-transform spectrometry (SWIFTS)-an approach based on direct intensity detection of a standing wave resulting from either reflection (as in the principle of colour photography by Gabriel Lippmann) or counterpropagative interference phenomenon-is expected to be able to overcome this drawback. Here, we present a SWIFTS-based spectrometer relying on an original optical near-field detection method in which optical nanoprobes are used to sample directly the evanescent standing wave in the waveguide. Combined with integrated optics, we report a way of reducing the volume of the spectrometer to a few hundreds of cubic wavelengths. This is the first attempt, using SWIFTS, to produce a very small integrated one-dimensional spectrometer suitable for applications where microspectrometers are essential

    A qualitative exploration of the acceptability of a cognitive behavioural therapy self-help book for people with psychosis in Nicaragua

    Get PDF
    Background: Cognitive Behavioural Therapy (CBT) self-help interventions have become a popular tool in High-Income Countries (HIC) to support people living with psychosis. There is limited research of this in Low– and Middle-Income Country (LMIC) contexts. We report findings of a qualitative investigation of a self-help book for psychosis in Nicaragua in Central America. Methods: Ten service users who self-identified as having psychosis were recruited from a mental health non-governmental organisation (NGO). Participants were given a Spanish version of a popular self-help book developed in the UK. They had four weeks to familiarise themselves with the book. Following this, we asked participants about their experiences of the book via an open ended questionnaire and a focus group discussion. Results: We conducted an inductive content analysis on the data. Evaluations of the book were positive. The book was considered easy to understand. The exercises were useful for coping with symptoms, as well as for recognising and managing relapse. Case studies were perceived useful in terms of reducing stigma and promoting self-acceptance. Discussion: The data highlight potential acceptability of CBT self-help books in the Nicaraguan context. We make recommendations for further research and evaluation to build on this signal of acceptability

    Children and older adults exhibit distinct sub-optimal cost-benefit functions when preparing to move their eyes and hands

    Get PDF
    "© 2015 Gonzalez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited"Numerous activities require an individual to respond quickly to the correct stimulus. The provision of advance information allows response priming but heightened responses can cause errors (responding too early or reacting to the wrong stimulus). Thus, a balance is required between the online cognitive mechanisms (inhibitory and anticipatory) used to prepare and execute a motor response at the appropriate time. We investigated the use of advance information in 71 participants across four different age groups: (i) children, (ii) young adults, (iii) middle-aged adults, and (iv) older adults. We implemented 'cued' and 'non-cued' conditions to assess age-related changes in saccadic and touch responses to targets in three movement conditions: (a) Eyes only; (b) Hands only; (c) Eyes and Hand. Children made less saccade errors compared to young adults, but they also exhibited longer response times in cued versus non-cued conditions. In contrast, older adults showed faster responses in cued conditions but exhibited more errors. The results indicate that young adults (18 -25 years) achieve an optimal balance between anticipation and execution. In contrast, children show benefits (few errors) and costs (slow responses) of good inhibition when preparing a motor response based on advance information; whilst older adults show the benefits and costs associated with a prospective response strategy (i.e., good anticipation)

    Cross validation of bi-modal health-related stress assessment

    Get PDF
    This study explores the feasibility of objective and ubiquitous stress assessment. 25 post-traumatic stress disorder patients participated in a controlled storytelling (ST) study and an ecologically valid reliving (RL) study. The two studies were meant to represent an early and a late therapy session, and each consisted of a "happy" and a "stress triggering" part. Two instruments were chosen to assess the stress level of the patients at various point in time during therapy: (i) speech, used as an objective and ubiquitous stress indicator and (ii) the subjective unit of distress (SUD), a clinically validated Likert scale. In total, 13 statistical parameters were derived from each of five speech features: amplitude, zero-crossings, power, high-frequency power, and pitch. To model the emotional state of the patients, 28 parameters were selected from this set by means of a linear regression model and, subsequently, compressed into 11 principal components. The SUD and speech model were cross-validated, using 3 machine learning algorithms. Between 90% (2 SUD levels) and 39% (10 SUD levels) correct classification was achieved. The two sessions could be discriminated in 89% (for ST) and 77% (for RL) of the cases. This report fills a gap between laboratory and clinical studies, and its results emphasize the usefulness of Computer Aided Diagnostics (CAD) for mental health care

    Organizational factors and depression management in community-based primary care settings

    Get PDF
    Abstract Background Evidence-based quality improvement models for depression have not been fully implemented in routine primary care settings. To date, few studies have examined the organizational factors associated with depression management in real-world primary care practice. To successfully implement quality improvement models for depression, there must be a better understanding of the relevant organizational structure and processes of the primary care setting. The objective of this study is to describe these organizational features of routine primary care practice, and the organization of depression care, using survey questions derived from an evidence-based framework. Methods We used this framework to implement a survey of 27 practices comprised of 49 unique offices within a large primary care practice network in western Pennsylvania. Survey questions addressed practice structure (e.g., human resources, leadership, information technology (IT) infrastructure, and external incentives) and process features (e.g., staff performance, degree of integrated depression care, and IT performance). Results The results of our survey demonstrated substantial variation across the practice network of organizational factors pertinent to implementation of evidence-based depression management. Notably, quality improvement capability and IT infrastructure were widespread, but specific application to depression care differed between practices, as did coordination and communication tasks surrounding depression treatment. Conclusions The primary care practices in the network that we surveyed are at differing stages in their organization and implementation of evidence-based depression management. Practical surveys such as this may serve to better direct implementation of these quality improvement strategies for depression by improving understanding of the organizational barriers and facilitators that exist within both practices and practice networks. In addition, survey information can inform efforts of individual primary care practices in customizing intervention strategies to improve depression management.http://deepblue.lib.umich.edu/bitstream/2027.42/78269/1/1748-5908-4-84.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78269/2/1748-5908-4-84-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78269/3/1748-5908-4-84.pdfPeer Reviewe
    corecore