Reconstruction of the neuromuscular junction connectome

Motivation: Unraveling the structure and behavior of the brain and central nervous system (CNS) has always been a major goal of neuroscience. Understanding the wiring diagrams of the neuromuscular junction connectomes (full connectivity of nervous system neuronal components) is a starting point for this, as it helps in the study of the organizational and developmental properties of the mammalian CNS. The phenomenon of synapse elimination during developmental stages of the neuronal circuitry is such an example. Due to the organizational specificity of the axons in the connectomes, it becomes important to label and extract individual axons for morphological analysis. Features such as axonal trajectories, their branching patterns, geometric information, the spatial relations of groups of axons, etc. are of great interests for neurobiologists in the study of wiring diagrams. However, due to the complexity of spatial structure of the axons, automatically tracking and reconstructing them from microscopy images in 3D is an unresolved problem. In this article, AxonTracker-3D, an interactive 3D axon tracking and labeling tool is built to obtain quantitative information by reconstruction of the axonal structures in the entire innervation field. The ease of use along with accuracy of results makes AxonTracker-3D an attractive tool to obtain valuable quantitative information from axon datasets

Colored Motifs Reveal Computational Building Blocks in the C. elegans Brain

Background: Complex networks can often be decomposed into less complex sub-networks whose structures can give hints about the functional organization of the network as a whole. However, these structural motifs can only tell one part of the functional story because in this analysis each node and edge is treated on an equal footing. In real networks, two motifs that are topologically identical but whose nodes perform very different functions will play very different roles in the network. Methodology/Principal Findings: Here, we combine structural information derived from the topology of the neuronal network of the nematode C. elegans with information about the biological function of these nodes, thus coloring nodes by function. We discover that particular colorations of motifs are significantly more abundant in the worm brain than expected by chance, and have particular computational functions that emphasize the feed-forward structure of information processing in the network, while evading feedback loops. Interneurons are strongly over-represented among the common motifs, supporting the notion that these motifs process and transduce the information from the sensor neurons towards the muscles. Some of the most common motifs identified in the search for significant colored motifs play a crucial role in the system of neurons controlling the worm's locomotion. Conclusions/Significance: The analysis of complex networks in terms of colored motifs combines two independent data sets to generate insight about these networks that cannot be obtained with either data set alone. The method is general and should allow a decomposition of any complex networks into its functional (rather than topological) motifs as long as both wiring and functional information is available

Translation and validation of the Cardiac Depression Scale to Arabic

Background The Cardiac Depression Scale (CDS) has been designed to measure depressive symptoms in patients with heart disease. There is no Arabic version of the CDS. We translated and validated the CDS in an Arabic sample of patients with heart disease. Methods Forward and back translation of the CDS was followed by assessment of cultural relevance and content validity. The Arabic version of the CDS (A-CDS) and the Arabic version of the Hospital Anxiety and Depression Scale (A-HADS) were then administered to 260 Arab in-patients with heart disease from 18 Arabic countries. Construct validity was assessed using exploratory factor analysis with polychoric correlations. Internal consistency was assessed using ordinal reliability alpha and item-to-factor polychoric correlations. Concurrent validity was assessed using Pearson's correlation coefficient between the A-CDS and the depression subscale of the A-HADS (A-HADS-D). Results Cultural relevance and content validity of the A-CDS were satisfactory. Exploratory factor analysis revealed three robust factors, without cross-loadings, that formed a single dimension. Internal consistency was high (ordinal reliability alpha for the total scale and the three factors were .94, .91, .86, and .87, respectively; item-to-factor correlations ranged from .77 to .91). Concurrent validity was high (r?=?.72). The A-CDS demonstrated a closer to normal distribution of scores than the A-HADS-D. Limitations Sensitivity and specificity of the A-CDS were not objectively assessed. Conclusions The A-CDS appears to be a valid and reliable instrument to measure depressive symptoms in a representative sample of Arab in-patients with heart disease

Semi-Automated Reconstruction of Neural Processes from Large Numbers of Fluorescence Images

We introduce a method for large scale reconstruction of complex bundles of neural processes from fluorescent image stacks. We imaged yellow fluorescent protein labeled axons that innervated a whole muscle, as well as dendrites in cerebral cortex, in transgenic mice, at the diffraction limit with a confocal microscope. Each image stack was digitally re-sampled along an orientation such that the majority of axons appeared in cross-section. A region growing algorithm was implemented in the open-source Reconstruct software and applied to the semi-automatic tracing of individual axons in three dimensions. The progression of region growing is constrained by user-specified criteria based on pixel values and object sizes, and the user has full control over the segmentation process. A full montage of reconstructed axons was assembled from the ∼200 individually reconstructed stacks. Average reconstruction speed is ∼0.5 mm per hour. We found an error rate in the automatic tracing mode of ∼1 error per 250 um of axonal length. We demonstrated the capacity of the program by reconstructing the connectome of motor axons in a small mouse muscle

A survey of visualisation for live cell imaging

Live cell imaging is an important biomedical research paradigm for studying dynamic cellular behaviour. Although phenotypic data derived from images are difficult to explore and analyse, some researchers have successfully addressed this with visualisation. Nonetheless, visualisation methods for live cell imaging data have been reported in an ad hoc and fragmented fashion. This leads to a knowledge gap where it is difficult for biologists and visualisation developers to evaluate the advantages and disadvantages of different visualisation methods, and for visualisation researchers to gain an overview of existing work to identify research priorities. To address this gap, we survey existing visualisation methods for live cell imaging from a visualisation research perspective for the first time. Based on recent visualisation theory, we perform a structured qualitative analysis of visualisation methods that includes characterising the domain and data, abstracting tasks, and describing visual encoding and interaction design. Based on our survey, we identify and discuss research gaps that future work should address: the broad analytical context of live cell imaging; the importance of behavioural comparisons; links with dynamic data visualisation; the consequences of different data modalities; shortcomings in interactive support; and, in addition to analysis, the value of the presentation of phenotypic data and insights to other stakeholders

Putting out the fires: Supervisors' experiences of introducing primary English in Saudi Arabia.

Teaching English to Young learners (TEYL) initiatives can represent an example of complex change (Fullan, 1992), whose classroom implementation implies those affected by the change learning new, or adjusting existing, practices and beliefs. Research (Levin and Fullan, 2008; Wedell, 2013) suggests that if contextually appropriate versions of complex change outcomes are to become visible in the majority of classrooms, both the parts of the change system (e.g. materials and assessment), and the way in which the people affected (change ‘partners’) carry out their roles, need to be as consistent as possible with change aims. Saudi Arabia introduced the teaching of English in the last year of primary level in 2004, and expanded it to the fourth year of schooling in 2011. This study uses the reported experiences of representatives from one key group of change ‘partners’: Saudi Primary English Supervisors, to explore aspects of the first six years of TEYL implementation. Their reports suggest widespread inconsistency during the first phase of implementation and little attempt to address the issues before launching the second phase. We suggest that acknowledging the value of these implementers' experiences and giving greater consideration to their suggestions, could help enable the second phase of implementation to become more consistent than the first

Dementia and Depression with Ischemic Heart Disease: A Population-Based Longitudinal Study Comparing Interventional Approaches to Medical Management

BACKGROUND: We compared the proportion of ischemic heart disease (IHD) patients newly diagnosed with dementia and depression across three treatment groups: percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) and medical management alone (IHD-medical). METHODS AND FINDINGS: De-identified, individual-level administrative records of health service use for the population of Manitoba, Canada (approximately 1.1 million) were examined. From April 1, 1993 to March 31, 1998, patients were identified with a diagnosis of IHD (ICD-9-CM codes). Index events of CABG or PCI were identified from April 1, 1998 to March 31, 2003. Outcomes were depression or dementia after the index event. Patients were followed forward to March 31, 2006 or until censored. Proportional hazards regression analysis was undertaken. Independent variables examined were age, sex, diabetes, hypertension and income quintile, medical management alone for IHD, or intervention by PCI or CABG. Age, sex, diabetes, and presence of hypertension were all strongly associated with the diagnosis of depression and dementia. There was no association with income quintile. Dementia was less frequent with PCI compared to medical management; (HR = 0.65; p = 0.017). CABG did not provide the same protective effect compared to medical management (HR = 0.90; p = 0.372). New diagnosis depression was more frequent with interventional approaches: PCI (n = 626; hazard ratio = 1.25; p = 0.028) and CABG (n = 1124, HR = 1.32; p = 0.0001) than non-interventional patients (n = 34,508). Subsequent CABG was nearly 16-fold higher (p<0.0001) and subsequent PCI was 22-fold higher (p<0.0001) for PCI-managed than CABG-managed patients. CONCLUSIONS: Patients managed with PCI had the lowest likelihood of dementia-only 65% of the risk for medical management alone. Both interventional approaches were associated with a higher risk of new diagnosed depression compared to medical management. Long-term myocardial revascularization was superior with CABG. These findings suggest that PCI may confer a long-term protective effect from dementia. The mechanism(s) of dementia protection requires elucidation