Deriving a multi-subject functional-connectivity atlas to inform connectome estimation

MICCAI 2014 preprintInternational audienceThe estimation of functional connectivity structure from functional neuroimaging data is an important step toward understanding the mechanisms of various brain diseases and building relevant biomarkers. Yet, such inferences have to deal with the low signal-to-noise ratio and the paucity of the data. With at our disposal a steadily growing volume of publicly available neuroimaging data, it is however possible to improve the estimation procedures involved in connectome mapping. In this work, we propose a novel learning scheme for functional connectivity based on sparse Gaussian graphical models that aims at minimizing the bias induced by the regularization used in the estimation, by carefully separating the estimation of the model support from the coefficients. Moreover, our strategy makes it possible to include new data with a limited computational cost. We illustrate the physiological relevance of the learned prior, that can be identified as a functional connectivity atlas, based on an experiment on 46 subjects of the Human Connectome Dataset

Objective identification and analysis of physiological and behavioral signs of schizophrenia

BACKGROUND: A patient\u27s physical activity is often used by psychiatrists to contribute to the diagnostic process for mental disorders. Typically, it is based mostly on self-reports or observations, and hardly ever upon actigraphy. Other signals related to physiology are rarely used, despite the fact that the autonomic nervous system is often affected by mental disorders. AIM: This study attempted to fuse physiological and physical activity data and discover features that are predictive for schizophrenia. METHOD: Continuous simultaneous heart rate (HR) and physical activity recordings were made on 16 individuals with schizophrenia and 19 healthy controls. Statistical characteristics of the recorded data were analyzed, as well as non-linear rest-activity measures and disorganization measures. RESULTS: Four most predictive features for schizophrenia were identified, namely, the standard deviation and mode of locomotor activity, dynamics of Multiscale Entropy change over scales of HR signal and the mean HR. A classifier trained on these features provided a cross-validation accuracy of 95.3% (AUC = 0.99) for differentiating between schizophrenia patients and controls, compared to 78.5 and 85.5% accuracy (AUC = 0.85 and AUC = 0.90) using only the HR or locomotor activity features. CONCLUSION: Physiological and physical activity signals provide complimentary information for assessment of mental health

Morphology and synaptic organization of non-dopaminergic nigral projections to the medio dorsal thalamic nucleus of the rat, a study by anterograde transport of PHA-L

Background: Mediodorsal (MD) thalamic nucleus, which is considered to take place between extra pyramidal and limbic feedback circuit, receives projective fibers from ventrolateral neurons of reticular part of substantia nigra (SNr). In order to better understand the influence and chemical reaction of these fibers upon MD nucleus, the morphology and synaptology of them were examined in the present study. Methods: Phaseolous vulgaris-leucoagglutin (PHA-L) was injected into substantia nigra pars reticulate. After 3-4 days, the sections of SNr injection site and MD nucleus were prepared. Then, we examined organization, morphology and, synaptology of PHA-L labeled SNr fibers that go to caudal and lateral part of MD thalamic nucleus. Results: At the electron microscopic level, the SNr terminals made synapses predominantly with the medium to small dendrites and far less frequently with soma and large dendrites. These terminals were packed with polymorphic synaptic vesicles and formed symmetrical synapses; furthermore, it has been already recognized that cortico straital fibers from sensory-motor cortex go to region of the SNr that give rise to the nigrothalamic fibers. Conclusion: This data suggest that upon the synaptic organization, morphology and chemical nature of GABAergic, SNr fibers may have different inhibitory influence on MD neurons regulating the thalamic output from MD to cerebral cortex in the control of limbic and extra pyramidal feedback system

Effect of intrathecal transplantation of adrenal medullary tissue on the sciatic nerve regeneration following chronic constriction injury in the rat

Introduction: It has been demonstrated that the adrenal medullary transplants into the spinal subarachnoid space can alleviate neuropathic pain behaviors. The aim of the present study was to test the possibility that histological changes of the sciatic nerve in a neuropathic model as well as sensory dysfunction are repaired by adrenal medullary transplantation. Material and Methods: Left sciatic nerve was ligated in three groups of rats by 4 loose ligatures (CCI). After one week of nerve constriction, rats of first group were implanted with adrenal medullary tissue (CCI + adrenal medulla) and rats of the second group with striated muscle at the level of L1-L2 (CCI + muscle). The third group received only left ligature (CCI) and in the fourth group the sciatic nerve was exposed and then muscle and skin sutured (sham). Behavioral assessment was evaluated before surgery and 2, 4, 7, 10, 14, 21, 28, 42, and 56 days after the onset of experiment. According to behavioral results, 4 rats in each group were anesthetized and then the distal part of sciatic nerve were isolated and prepared for histological quantitative investigation of nerve regeneration. Results: The results showed that CCI was accompanied with hyperalgesia and morphological changes in the distal part of sciatic nerve. In animals with adrenal medullary transplantation, not only hyperalgesia was markedly reduced or even eliminated, but also the number of myelinated fibers in the distal segment of nerve increased to nearly normal. Conclusions: Our findings showed that the implantation of adrenal medullary tissue might have caused regeneration of ligated nerves as well as alleviation of pain behavior

A triblock terpolymer vs. blends of diblock copolymers for nanocapsules addressed by three independent stimuli

The chemical structure of triblock terpolymers is exploited to achieve polymer nanocapsules responsive to three different stimuli.</p

New East Manchester: urban renaissance or urban opportunism?

In this paper we ask how a shrinking city responds when faced with a perforated urban fabric. Drawing on Manchester’s response to its perforated eastern flank - and informed by a parallel study of Leipzig - we use the city’s current approach to critique urban regeneration policy in England. Urban renaissance holds out the promise of delivering more sustainable - that is more compact, more inclusive and more equitable - cities. However, the Manchester study demonstrated that the attempt to stem population loss from the city is at best fragile, despite a raft of policies now in place to support urban renaissance in England. It is argued here that Manchester like Leipzig is likely to face an ongoing battle to attract residents back from their suburban hinterlands. This is especially true of the family market that we identify as being an important element for long-term sustainable population growth in both cities. We use the case of New East Manchester to consider how discourses linked to urban renaissance – particularly those that link urbanism with greater densities - rule out some of the options available to Leipzig, namely, managing the long-term perforation of the city. We demonstrate that while Manchester is inevitably committed to the urban renaissance agenda, in practice New East Manchester demonstrates a far more pragmatic – but equally unavoidable – approach. This we attribute to the gap between renaissance and regeneration described by Amin et al (2000) who define the former as urbanism for the middle class and the latter as urbanism for the working class. While this opportunistic approach may ultimately succeed in producing development on the ground, it will not address the fundamental, and chronic, problem; the combination of push and pull that sees families relocating to suburban areas. Thus, if existing communities in East Manchester are to have their area buoyed up – or sustained - by incomers, and especially families, with greater levels of social capital and higher incomes urban policy in England will have to be challenged

Developing a methodology for three-dimensional correlation of PET–CT images and whole-mount histopathology in non-small-cell lung cancer

Background: Understanding the three-dimensional (3D) volumetric relationship between imaging and functional or histopathologic heterogeneity of tumours is a key concept in the development of image-guided radiotherapy. Our aim was to develop a methodologic framework to enable the reconstruction of resected lung specimens containing non-small-cell lung cancer (NSCLC), to register the result in 3D with diagnostic imaging, and to import the reconstruction into a radiation treatment planning system. Methods and Results: We recruited 12 patients for an investigation of radiology-pathology correlation (RPC) in NSCLC. Before resection, imaging by positron emission tomography (PET) or computed tomography (CT) was obtained. Resected specimens were formalin-fixed for 1-24 hours before sectioning at 3-mm to 10-mm intervals. To try to retain the original shape, we embedded the specimens in agar before sectioning. Consecutive sections were laid out for photography and manually adjusted to maintain shape. Following embedding, the tissue blocks underwent whole-mount sectioning (4-μm sections) and staining with hematoxylin and eosin. Large histopathology slides were used to whole-mount entire sections for digitization. The correct sequence was maintained to assist in subsequent reconstruction. Using Photoshop (Adobe Systems Incorporated, San Jose, CA, U.S.A.), contours were placed on the photographic images to represent the external borders of the section and the extent of macroscopic disease. Sections were stacked in sequence and manually oriented in Photoshop. The macroscopic tumour contours were then transferred to MATLAB (The Mathworks, Natick, MA, U.S.A.) and stacked, producing 3D surface renderings of the resected specimen and embedded gross tumour. To evaluate the microscopic extent of disease, customized "tile-based" and commercial confocal panoramic laser scanning (TISSUEscope: Biomedical Photometrics, Waterloo, ON) systems were used to generate digital images of whole-mount histopathology sections. Using the digital whole-mount images and imaging software, we contoured the gross and microscopic extent of disease. Two methods of registering pathology and imaging were used. First, selected PET and CT images were transferred into Photoshop, where they were contoured, stacked, and reconstructed. After importing the pathology and the imaging contours to MATLAB, the contours were reconstructed, manually rotated, and rigidly registered. In the second method, MATLAB tumour renderings were exported to a software platform for manual registration with the original PET and CT images in multiple planes. Data from this software platform were then exported to the Pinnacle radiation treatment planning system in DICOM (Digital Imaging and Communications in Medicine) format. Conclusions: There is no one definitive method for 3D volumetric RPC in NSCLC. An innovative approach to the 3D reconstruction of resected NSCLC specimens incorporates agar embedding of the specimen and whole-mount digital histopathology. The reconstructions can be rigidly and manually registered to imaging modalities such as CT and PET and exported to a radiation treatment planning system

Prediction and quality assessment of protein quaternary structure models using the MultiFOLD2 and ModFOLDdock2 servers

Understanding the structures of protein complexes is pivotal for breakthroughs in health, agriculture, bioengineering, and beyond. MultiFOLD2 and ModFOLDdock2 are leading servers for protein quaternary structure prediction and model quality assessment, respectively. MultiFOLD2 includes integrated stoichiometry prediction for quaternary structures and improved sampling and scoring, leading to high performance in continuous independent benchmarks such as CAMEO. ModFOLDdock2 uses a hybrid consensus approach to generate global and local quality scores for predicted quaternary structures. ModFOLDdock2 is integrated with MultiFOLD2 while also being available as a stand-alone server, enabling the independent evaluation of quaternary structure models from any source. Both servers have been independently rigorously evaluated, demonstrating high performance and ranking among the top servers in their respective categories in the recent CASP16 experiment. The MultiFOLD2 and ModFOLDdock2 servers are freely accessible through user-friendly web interfaces at https://www.reading.ac.uk/bioinf/