Biology subjects

Coca, D.

Publications and source records attributed to Coca, D..

4 recordsLinked to original sources

bioRxiv2023

Ageing-related defects in macrophage function are driven by MYC and USF1 transcriptional programmes

Macrophages are central innate immune cells whose function declines with age. The molecular mechanisms underlying age-related immunity changes remain poorly understood, particularly in human macrophages. We report a substantial reduction in phagocytosis, migration and chemotaxis in human monocyte-derived macrophages (MDMs) from older (>50 years) compared with younger (18-30 years) donors, alongside downregulation of transcription factors MYC and USF1 with age. In MDMs from young donors, knockdown of MYC or USF1 decreased phagocytosis and chemotaxis and altered expression of genes associated with these functions, as well as adhesion and extracellular matrix remodelling. A concordant dysregulation of MYC and USF1 target genes was also seen in MDMs from older donors. Furthermore, older age and loss of either MYC or USF1 in MDMs led to an increased cell size, altered morphology and reduced actin content. Together, these results define MYC and USF1 as key drivers of MDM age-related functional decline and identify downstream targets to improve macrophage function in ageing.

immunology↗

bioRxiv2019

The Fruit Fly Brain Observatory: From Structure to Function

The fruit fly is a key model organism for studying the activity of interconnected brain circuits. A large scattered global research community of neurobiologists and neurogeneticists, computational and theoretical neuroscientists, and computer scientists and engineers has been developing a vast trove of experimental and modeling data that has yet to be distilled into new knowledge and understanding of the functional logic of the brain. Developing open shared models, modelling tools and data repositories that can be accessed from anywhere in the world is the necessary engine for accelerating our understanding of how the brain works.\n\nTo that end we developed the Fruit Fly Brain Observatory (FFBO), the next generation open-source platform to support open, collaborative Drosophila neuroscience research. FFBO provides a (i) hub for storing and integrating fruit fly brain research data from multiple data sources worldwide, (ii) unified repository of tools and methods to build, emulate and compare fruit fly brain models in health and disease, and (iii) an open framework for fruit fly brain data processing and model execution. FFBO provides access to application tools for visualizing, configuring, simulating and analyzing computational models of brain circuits of the (i) cell type map, (ii) connectome, (iii) synaptome, and (iv) activity map using intuitive queries in plain English. Tools are provided to extract the function inherent in these structural maps. All applications can be accessed with any modern browser.

neuroscience↗

bioRxiv2016

The Fruit Fly Brain Observatory: from structure to function

The Fruit Fly Brain Observatory (FFBO) is a collaborative effort between experimentalists, theorists and computational neuroscientists at Columbia University, National Tsing Hua University and Sheffield University with the goal to (i) create an open platform for the emulation and biological validation of fruit fly brain models in health and disease, (ii) standardize tools and methods for graphical rendering, representation and manipulation of brain circuits, (iii) standardize tools for representation of fruit fly brain data and its abstractions and support for natural language queries, (iv) create a focus for the neuroscience community with interests in the fruit fly brain and encourage the sharing of fruit fly brain structural data and executable code worldwide. NeuroNLP and NeuroGFX, two key FFBO applications, aim to address two major challenges, respectively: i) seamlessly integrate structural and genetic data from multiple sources that can be intuitively queried, effectively visualized and extensively manipulated, ii) devise executable brain circuit models anchored in structural data for understanding and developing novel hypotheses about brain function. NeuroNLP enables researchers to use plain English (or other languages) to probe biological data that are integrated into a novel database system, called NeuroArch, that we developed for integrating biological and abstract data models of the fruit fly brain. With powerful 3D graphical visualization, NeuroNLP presents a highly accessible portal for the fruit fly brain data. NeuroGFX provides users highly intuitive tools to execute neural circuit models with Neurokernel, an open-source platform for emulating the fruit fly brain, with full data support from the NeuroArch database and visualization support from an interactive graphical interface. Brain circuits can be configured with high flexibility and investigated on multiple levels, e.g., whole brain, neuropil, and local circuit levels. The FFBO is publicly available and accessible at http://fruitflybrain.org from any modern web browsers, including those running on smartphones.

neuroscience↗

bioRxiv2016

NeuroNLP: a natural language portal for aggregated fruit fly brain data

NeuroNLP, is a key application on the Fruit Fly Brain Observatory platform (FFBO, http://fruitflybrain.org), that provides a modern web-based portal for navigating fruit fly brain circuit data. Increases in the availability and scale of fruit fly connectome data, demand new, scalable and accessible methods to facilitate investigation into the functions of the latest complex circuits being uncovered. NeuroNLP enables in-depth exploration and investigation of the structure of brain circuits, using intuitive natural language queries that are capable of revealing the latent structure and information, obscured due to expansive yet independent data sources. NeuroNLP is built on top of a database system call NeuroArch that codifies knowledge about the fruit fly brain circuits, spanning multiple sources. Users can probe biological circuits in the NeuroArch database with plain English queries, such as \"show glutamatergic local neurons in the left antennal lobe\" and \"show neurons with dendrites in the left mushroom body and axons in the fan-shaped body\". This simple yet powerful interface replaces the usual, cumbersome checkboxes and dropdown menus prevalent in todays neurobiological databases. Equipped with powerful 3D visualization, NeuroNLP standardizes tools and methods for graphical rendering, representation, and manipulation of brain circuits, while integrating with existing databases such as the FlyCircuit. The userfriendly graphical user interface complements the natural language queries with additional controls for exploring the connectivity of neurons and neural circuits. Designed with an open-source, modular structure, it is highly scalable/flexible/extensible to additional databases or to switch between databases and supports the creation of additional parsers for other languages. By supporting access through a web browser from any modern laptop or smartphone, NeuroNLP significantly increases the accessibility of fruit fly brain data and improves the impact of the data in both scientific and educational exploration.

neuroscience↗