7,695 research outputs found

    On the potential for mapping apparent neural soma density via a clinically viable diffusion MRI protocol

    Get PDF
    Diffusion MRI is a valuable tool for probing tissue microstructure in the brain noninvasively. Today, model-based techniques are widely available and used for white matter characterisation where their development is relatively mature. Conversely, tissue modelling in grey matter is more challenging, and no generally accepted models exist. With advances in measurement technology and modelling efforts, a clinically viable technique that reveals salient features of grey matter microstructure, such as the density of quasi-spherical cell bodies and quasi-cylindrical cell projections, is an exciting prospect. As a step towards capturing the microscopic architecture of grey matter in clinically feasible settings, this work uses a biophysical model that is designed to disentangle the diffusion signatures of spherical and cylindrical structures in the presence of orientation heterogeneity, and takes advantage of B-tensor encoding measurements, which provide additional sensitivity compared to standard single diffusion encoding sequences. For the fast and robust estimation of microstructural parameters, we leverage recent advances in machine learning and replace conventional fitting techniques with an artificial neural network that fits complex biophysical models within seconds. Our results demonstrate apparent markers of spherical and cylindrical geometries in healthy human subjects, and in particular an increased volume fraction of spherical compartments in grey matter compared to white matter. We evaluate the extent to which spherical and cylindrical geometries may be interpreted as correlates of neural soma and neural projections, respectively, and quantify parameter estimation errors in the presence of various departures from the modelling assumptions. While further work is necessary to translate the ideas presented in this work to the clinic, we suggest that biomarkers focussing on quasi-spherical cellular geometries may be valuable for the enhanced assessment of neurodevelopmental disorders and neurodegenerative diseases

    Modeling Fibrillogenesis of Collagen-Mimetic Molecules

    Get PDF
    One of the most robust examples of self-assembly in living organisms is the formation of collagen architectures. Collagen type I molecules are a crucial component of the extracellular matrix, where they self-assemble into fibrils of well-defined axial striped patterns. This striped fibrillar pattern is preserved across the animal kingdom and is important for the determination of cell phenotype, cell adhesion, and tissue regulation and signaling. The understanding of the physical processes that determine such a robust morphology of self-assembled collagen fibrils is currently almost completely missing. Here, we develop a minimal coarse-grained computational model to identify the physical principles of the assembly of collagen-mimetic molecules. We find that screened electrostatic interactions can drive the formation of collagen-like filaments of well-defined striped morphologies. The fibril axial pattern is determined solely by the distribution of charges on the molecule and is robust to the changes in protein concentration, monomer rigidity, and environmental conditions. We show that the striped fibrillar pattern cannot be easily predicted from the interactions between two monomers but is an emergent result of multibody interactions. Our results can help address collagen remodeling in diseases and aging and guide the design of collagen scaffolds for biotechnological applications

    Use of farm buildings by wild badgers: implications for the transmission of bovine tuberculosis

    Get PDF
    Diseases transmitted from wildlife to livestock or people may be managed more effectively if it is known where transmission occurs. In Britain, farm buildings have been proposed as important sites of Mycobacterium bovis transmission between wild badgers (Meles meles) and cattle, contributing to the maintenance of bovine tuberculosis (TB). Farmers are therefore advised to exclude badgers from buildings. We used GPS-collars and remote cameras to characterise badgers’ use of farm buildings at four TB-affected sites in southwestern Britain. Across 54 GPS-collared badgers, 99.8% of locations fell ≥3m from farm buildings. Remote cameras deployed in feed stores recorded just 12 nights with badger visits among 3,134 store-nights of monitoring. GPS-collared badgers used space near farm buildings less than expected based on availability, significantly preferring land ≥100m from buildings. There was no positive association between badgers’ use of farm buildings and the infection status of either badgers or cattle. Six GPS-collared badgers which regularly visited farm buildings all tested negative for M. bovis. Overall, test-positive badgers spent less time close to farm buildings than did test-negative animals. Badger visits to farm buildings were more frequent where badger population densities were high. Our findings suggest that, while buildings may offer important opportunities for M. bovis transmission between badgers and cattle, building use by badgers is not a prerequisite for such transmission. Identifying ways to minimise infectious contact between badgers and cattle away from buildings is therefore a management priority

    Palliative medicine practitioners' views on the concept of depression in the palliative care setting

    Get PDF
    Background: Despite its clinical importance in palliative care, depression remains an ambiguous concept. Objective: The purpose of this study was to explore how medical practitioners working in palliative care conceptualize depression in that setting. Design: Medical practitioners who attended a palliative medicine conference (N=185) were invited to respond to a questionnaire, which explored their views on the concept of depression in the palliative care context. Descriptive statistics were used to summarize responses, and comparison between groups was conducted using nonparametric statistics. Themes in free-text comments were identified. Results: Seventy-nine responses were obtained (response rate 43%). Depression was not a unified concept, but was generally considered to be an illness with psychological, spiritual, and existential causes. Respondents were more uncertain about depression being an illness in the palliative care setting compared with other settings, and were ambivalent about its causality. Treatment preferences leaned towards psychological interventions. Depression being different in the palliative care setting was a theme. It was considered to be more prevalent, different in quality, harder to define, and associated with greater barriers to diagnosis and treatment. Conceptual differences were associated with the respondents' area of work, work position, duration of practice, and previous mental health training. Conclusions: Depression in the palliative care setting is a variable concept for palliative medicine practitioners. The conceptual diversity and complexities of depression in this setting must be acknowledged and further explored in order to develop nuanced approaches in clinical practice and in research.Felicity Ng, Gregory B. Crawford and Anna Chur-Hanse

    Establishing the precise evolutionary history of a gene improves prediction of disease-causing missense mutations

    Get PDF
    PURPOSE: Predicting the phenotypic effects of mutations has become an important application in clinical genetic diagnostics. Computational tools evaluate the behavior of the variant over evolutionary time and assume that variations seen during the course of evolution are probably benign in humans. However, current tools do not take into account orthologous/paralogous relationships. Paralogs have dramatically different roles in Mendelian diseases. For example, whereas inactivating mutations in the NPC1 gene cause the neurodegenerative disorder Niemann-Pick C, inactivating mutations in its paralog NPC1L1 are not disease-causing and, moreover, are implicated in protection from coronary heart disease. METHODS: We identified major events in NPC1 evolution and revealed and compared orthologs and paralogs of the human NPC1 gene through phylogenetic and protein sequence analyses. We predicted whether an amino acid substitution affects protein function by reducing the organism’s fitness. RESULTS: Removing the paralogs and distant homologs improved the overall performance of categorizing disease-causing and benign amino acid substitutions. CONCLUSION: The results show that a thorough evolutionary analysis followed by identification of orthologs improves the accuracy in predicting disease-causing missense mutations. We anticipate that this approach will be used as a reference in the interpretation of variants in other genetic diseases as well. Genet Med 18 10, 1029–1036

    Direct observation of molecular cooperativity near the glass transition

    Full text link
    We describe direct observations of molecular cooperativity near the glass transition in poly-vinyl-acetate (PVAc), through nanometer-scale probing of dielectric fluctuations. Molecular clusters switched spontaneously between two to four distinct configurations, producing complex random-telegraph-signals (RTS). Analysis of the RTS and their power spectra shows that individual clusters exhibit both transient dynamical heterogeneity and non-exponential kinetics.Comment: 14 pages pdf, need Acrobat Reade

    Theory of Multidimensional Solitons

    Full text link
    We review a number of topics germane to higher-dimensional solitons in Bose-Einstein condensates. For dark solitons, we discuss dark band and planar solitons; ring dark solitons and spherical shell solitons; solitary waves in restricted geometries; vortex rings and rarefaction pulses; and multi-component Bose-Einstein condensates. For bright solitons, we discuss instability, stability, and metastability; bright soliton engineering, including pulsed atom lasers; solitons in a thermal bath; soliton-soliton interactions; and bright ring solitons and quantum vortices. A thorough reference list is included.Comment: review paper, to appear as Chapter 5a in "Emergent Nonlinear Phenomena in Bose-Einstein Condensates: Theory and Experiment," edited by P. G. Kevrekidis, D. J. Frantzeskakis, and R. Carretero-Gonzalez (Springer-Verlag

    Author Correction: iLoF: An intelligent Lab on Fiber Approach for Human Cancer Single-Cell Type Identification

    Get PDF
    An amendment to this paper has been published and can be accessed via a link at the top of the paper.This work was partially funded by the projects NanoSTIMA and NORTE-01-0145-FEDER-000029, both supported by the North Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, and through the European Regional Development Fund (ERDF); and by the Portuguese Foundation for Science and Technology, within the scope of the PhD grant PD/BD/135023/2017 and the projects: PTDC/BBB-EBI/0567/2014 (to CAR) and UID/BIM/04293/2013. It was also funded by FEDER funds through the Operational Programme for Competitiveness Factors-COMPETE (POCI-01-0145-FEDER-016585; POCI-01-0145-FEDER-007274; PPBI-POCI-01-0145-FEDER-022122). MB acknowledges the Marie Sklodowska-Curie grant agreement No. 748880
    • …
    corecore