Biology subjects

Garcia-Garcia, R.

Publications and source records attributed to Garcia-Garcia, R..

3 recordsLinked to original sources

bioRxiv2023

MAPK/MAK/MRK overlapping kinase (MOK) controls microglial inflammatory/type-I IFN responses via Brd4 and is involved in ALS pathophysiology

Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease affecting motor neurons and characterized by microglia-mediated neurotoxic inflammation whose underlying mechanisms remain incompletely understood. In this work we reveal that MAPK/MAK/MRK overlapping kinase (MOK), with unknown physiological substrate, displays an immune function by controlling inflammatory and type-I IFN responses in microglia which are detrimental to primary motor neurons. Moreover, we uncover the epigenetic reader bromodomain-containing protein 4 (Brd4) as the first molecule regulated by MOK, by promoting Ser492-phospho-Brd4 levels. We further demonstrate that MOK regulates Brd4 functions by supporting its binding to cytokine gene promoters, therefore enabling innate immune responses. Remarkably, we show that MOK levels are increased in ALS spinal cord, particularly in microglial cells, and that administration of a chemical MOK-inhibitor to ALS model mice is able to modulate Ser492-phospho-Brd4 levels, suppress microglial activation and modify disease course, indicating a pathophysiological role of MOK kinase in ALS and neuroinflammation.

neuroscience↗

bioRxiv2021

Plant-insect chemical communication in ecological communities: an information theory perspective

Cross-species communication, where signals are sent by one species and perceived by others, is one of the most intriguing types of communication that functionally links different species to form complex ecological networks. Yet, global changes and human activities can affect communication by increasing the fluctuations of species composition and phenology, altering signal profiles and intensity, and introducing noises. So far, most studies on cross-species communication have focused on a few specific species isolated from ecological communities. Scaling up investigations of cross-species communication to the community level is currently hampered by a lack of conceptual and practical methodologies. Here, we propose an interdisciplinary framework based on information theory to investigate mechanisms shaping cross-species communication at the community level. We use plants and insects, the cornerstones of most ecosystems, as a showcase; and focus on chemical communication as the key communication channel. We first introduce some basic concepts of information theory, then we illustrate information patterns in plant-insect chemical communication, followed by a further exploration of how to integrate information theory into ecological and evolutionary processes to form testable mechanistic hypotheses. We conclude by highlighting the importance of community-level information as a vehicle to better understand the maintenance of ecological systems, especially when facing rapid global changes.

ecology↗

bioRxiv2019

Linking lineage and population observables in biological branching processes

Using a population dynamics inspired by an ensemble of growing cells, a set of fluctuation theorems linking observables measured at the lineage and population levels are derived. One of these relations implies inequalities comparing the population doubling time with the mean generation time at the lineage or population levels. We argue that testing these inequalities provides useful insights into the underlying mechanism controlling the division rate in such branching processes.

biophysics↗