5 results on '"Luca, C. D."'
Search Results
2. Cobrawap: a modular cortical wave analysis pipeline for heterogeneous data
- Author
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Gutzen, R., Bonis, G. D., Grün, S., Davison, A., Paolucci, P. S., Denker, M., Pastorelli, E., Capone, C., Luca, C. D., Mascaro, A. L. A., Resta, F., Pavone, F. S., Sanchez-Vives, M. V., and Mattia, M.
- Abstract
Introduction:An unprecedented richness of data and methodologies enables more detailed access to neural processes but also poses the challenge to combine insights across experiments, species, and measurement techniques. While different experimental recording modalities offer complementary views onto the brain, their data analysis approaches and workflows are often too specific to compare the results rigorously. However, this challenge also promises new avenues of scientific progress. By aligning existing data and analyses from different sources in a reusable workflow we can build a broader basis for meta-studies, contextualization of individual studies, and model validation.Here, we showcase such an analysis pipeline with the application to cortical wave activity in the delta (‘slow waves’) and beta range. Cortical waves can be prominently observed in a variety of heterogeneous data [1,2] and a plethora of analytical methods exist that we aim to interface within a consistent framework: the ‘collaborative brain wave analysis pipeline’ (CobraWap).Methods:The design of CobraWap is based on modular building blocks that provide implementations of analysis methods and processing steps. These blocks are grouped in task-specific stages, e.g., data entry, data processing, trigger detection, wave detection, wave characterization. By letting the pipeline match the input and output format requirements for each of these pipeline components, defining a workflow becomes a matter of selecting a combination of stages and blocks to be applied. This flexibility is employed to converge the heterogeneous data to a common description level of wave activity, from which then common characteristic measures, such as velocity, direction, inter-wave intervals, or wave type classifications, can be derived and quantitatively compared across the data. We demonstrate the versatility of the pipeline with multiple datasets of ECoG [3] and calcium imaging recordings [4] of anesthetized mice, and Utah-array recordings of awake behaving macaques [e.g. 5]. Further, we integrate standard analysis methods from the literature to serve the requirements of a wide range of datasets and research questions. To emphasize the reusability and extendability of each of the pipeline components, the pipeline builds entirely on open-source solutions, such as the workflow manager Snakemake (RRID:SCR_003475), the Neo (RRID:SCR_000634) library for data representation [6], the Elephant (RRID:SCR_003833) analysis toolbox, and the EBRAINS Knowledge Graph (https://kg.ebrains.eu) for capturing outputs of the pipeline execution.Results:The pipeline design promotes the creation of application-tailored and reproducible analysis workflows for many datasets. We demonstrate this “big-data'' approach by investigating dataset-specific parameters across different experiments. For example, we evaluate the influences of the type and dose of anesthesia or the measurement modality and their temporal and spatial resolution on the characteristics of slow waves (e.g., wave velocities) and show that we can replicate corresponding findings from the literature [7,8,9,10].Just as applying the same methods to different data enables a fair comparison between datasets, the pipeline equally enables analyzing the same data with different methods to benchmark their influence on the resulting wave detection and characterization. Finally, we adapt the pipeline for the analysis of beta waves and discuss how the individual elements can be reused, rearranged, or extended to help derive analysis workflows for similar research endeavors and amplify collaborative research.Conclusions:While there are growing efforts in formalizing how neuroscientific data is represented and stored, we here present the benefits of furthermore formalizing the analysis workflows, leveraging the benefits of the diversity in data and methods towards easier collaboration and a cumulative understanding of brain function. REFERENCES[1] Adamantidis, A. R., Herrera C. G., and Gent T. C. (2019) "Oscillating circuitries in the sleeping brain." Nature Reviews Neuroscience 1-17. doi: 10.1038/s41583-019-0223-4[2] Muller, L. et al. (2018). “Cortical Travelling Waves: Mechanisms and Computational Principles.” Nature Reviews Neuroscience 19 (5): 255–68. doi: 10.1038/nrn.2018.20.[3] Sanchez-Vives, M. (2019) “Cortical activity features in transgenic mouse models of cognitive deficits (Williams Beuren Syndrome)” [Data set]. EBRAINS. doi: 10.25493/DZWT-1T8; Sanchez-Vives, M. (2019) "Cortical activity features in transgenic mouse models of cognitive deficits (Williams Beuren Syndrome)" EBRAINS. doi: 10.25493/ANF9-EG3[4] Resta, F., Allegra Mascaro, A. L., & Pavone, F. (2020) "Study of Slow Waves (SWs) propagation through wide-field calcium imaging of the right cortical hemisphere of GCaMP6f mice" EBRAINS. doi: 10.25493/3E6Y-E8G; Resta, F., Allegra Mascaro, A. L., & Pavone, F. (2021) "Study of Slow Waves (SWs) propagation through wide-field calcium imaging of the right cortical hemisphere of GCaMP6f mice (v2)" EBRAINS. doi: 10.25493/QFZK-FXS; Resta, F., [5] Allegra Mascaro, A. L., & Pavone, F. (2020) "Wide-field calcium imaging of the right cortical hemisphere of GCaMP6f mice at different anesthesia levels" EBRAINS. doi: 10.25493/XJR8-QCA[6] Brochier, T. et al. (2018) “Massively Parallel Recordings in Macaque Motor Cortex during an Instructed Delayed Reach-to-Grasp Task.” Scientific Data 5 (1): 180055. doi: 10.1038/sdata.2018.55.[7] Garcia, S. et al. (2014) “Neo: an object model for handling electrophysiology data in multiple formats.” Frontiers in Neuroinformatics 8:10. doi: 10.3389/fninf.2014.00010[8] De Bonis, G. et al. (2019) "Analysis pipeline for extracting features of cortical slow oscillations". Frontiers in Systems Neuroscience 13:70. doi: 10.3389/fnsys.2019.00070[9] Celotto, M. et al. (2020) “Analysis and Model of Cortical Slow Waves Acquired with Optical Techniques”. Methods and Protocols 3.1:14. doi: 10.3390/mps3010014[10] Dasilva, M., et al. (2020). Modulation of cortical slow oscillations and complexity across anesthesia levels. NeuroImage, 224, 117415. doi: 10.1016/j.neuroimage.2020.117415[11] Liang, Y. (2021). “Cortex-Wide Dynamics of Intrinsic Electrical Activities: Propagating Waves and Their Interactions.” Journal of Neuroscience 41 (16): 3665–78. doi: 10.1523/JNEUROSCI.0623-20.2021
- Published
- 2022
3. Targeting cancer stem cells in medulloblastoma by inhibiting AMBRA1 dual function in autophagy and STAT3 signalling
- Author
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Nazio, F., Po, A., Abballe, L., Ballabio, C., Diomedi Camassei, F., Bordi, Matteo, Camera, A., Caruso, S., Caruana, I., Pezzullo, M., Ferraina, C., Milletti, G., Gianesello, M., Reddel, S., De Luca, C. D., Ceglie, D., Marinelli, S., Campello, S., Papaleo, E., Miele, E., Cacchione, A., Carai, A., Vinci, M., Velardi, E., De Angelis, B., Tiberi, L., Quintarelli, C., Mastronuzzi, A., Ferretti, E., Locatelli, Franco, Cecconi, Francesco, Bordi M. (ORCID:0000-0001-8207-8546), Locatelli F. (ORCID:0000-0002-7976-3654), Cecconi F. (ORCID:0000-0002-5614-4359), Nazio, F., Po, A., Abballe, L., Ballabio, C., Diomedi Camassei, F., Bordi, Matteo, Camera, A., Caruso, S., Caruana, I., Pezzullo, M., Ferraina, C., Milletti, G., Gianesello, M., Reddel, S., De Luca, C. D., Ceglie, D., Marinelli, S., Campello, S., Papaleo, E., Miele, E., Cacchione, A., Carai, A., Vinci, M., Velardi, E., De Angelis, B., Tiberi, L., Quintarelli, C., Mastronuzzi, A., Ferretti, E., Locatelli, Franco, Cecconi, Francesco, Bordi M. (ORCID:0000-0001-8207-8546), Locatelli F. (ORCID:0000-0002-7976-3654), and Cecconi F. (ORCID:0000-0002-5614-4359)
- Abstract
Medulloblastoma (MB) is a childhood malignant brain tumour comprising four main subgroups characterized by different genetic alterations and rate of mortality. Among MB subgroups, patients with enhanced levels of the c-MYC oncogene (MBGroup3) have the poorest prognosis. Here we identify a previously unrecognized role of the pro-autophagy factor AMBRA1 in regulating MB. We demonstrate that AMBRA1 expression depends on c-MYC levels and correlates with Group 3 patient poor prognosis; also, knockdown of AMBRA1 reduces MB stem potential, growth and migration of MBGroup3 stem cells. At a molecular level, AMBRA1 mediates these effects by suppressing SOCS3, an inhibitor of STAT3 activation. Importantly, pharmacological inhibition of autophagy profoundly affects both stem and invasion potential of MBGroup3 stem cells, and a combined anti-autophagy and anti-STAT3 approach impacts the MBGroup3 outcome. Taken together, our data support the c-MYC/AMBRA1/STAT3 axis as a strong oncogenic signalling pathway with significance for both patient stratification strategies and targeted treatments of MBGroup3.
- Published
- 2021
4. Thymic Function and T-Cell Receptor Repertoire Diversity: Implications for Patient Response to Checkpoint Blockade Immunotherapy
- Author
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Cardinale, A., De Luca, C. D., Locatelli, Franco, Velardi, E., Locatelli F. (ORCID:0000-0002-7976-3654), Cardinale, A., De Luca, C. D., Locatelli, Franco, Velardi, E., and Locatelli F. (ORCID:0000-0002-7976-3654)
- Abstract
The capacity of T cells to recognize and mount an immune response against tumor antigens depends on the large diversity of the T-cell receptor (TCR) repertoire generated in the thymus during the process of T-cell development. However, this process is dramatically impaired by immunological insults, such as that caused by cytoreductive cancer therapies and infections, and by the physiological decline of thymic function with age. Defective thymic function and a skewed TCR repertoire can have significant clinical consequences. The presence of an adequate pool of T cells capable of recognizing specific tumor antigens is a prerequisite for the success of cancer immunotherapy using checkpoint blockade therapy. However, while this approach has improved the chances of survival of patients with different types of cancer, a large proportion of them do not respond. The limited response rate to checkpoint blockade therapy may be linked to a suboptimal TCR repertoire in cancer patients prior to therapy. Here, we focus on the role of the thymus in shaping the T-cell pool in health and disease, discuss how the TCR repertoire influences patients’ response to checkpoint blockade therapy and highlight approaches able to manipulate thymic function to enhance anti-tumor immunity.
- Published
- 2021
5. Approaches to the catalytic mechanism of mitochondrial monoamine oxidase.
- Author
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Hellerman L, Chuang HY, and De Luca CD
- Subjects
- Amines, Benzyl Compounds, Catalysis, Flavins analysis, Kidney cytology, Kidney enzymology, Kinetics, Models, Chemical, Monoamine Oxidase Inhibitors, Oxidation-Reduction, Pargyline, Spectrophotometry, Structure-Activity Relationship, Mitochondria enzymology, Monoamine Oxidase analysis
- Published
- 1972
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