32 research outputs found
Exploring the potential of cell-based models in simulating tissue biophysics in plant morphogenesis: the case of woody tissues.
This thesis considers the status of computational modelling in plant biology. After a brief introduction to modelling in biology, the reader is introduced to different approaches and tool. Among them, cell-based modelling is chosen to first model the effect of cell wall mechanics over tissue growth, and then xylogenesis of a generic conifer is simulated. In order to do so, the VirtualLeaf modelling framework has been used and extended with a description of the mechanical effects of thickness over cell dynamics. The frameworks proved itself a good tool for modeling such dynamics, and the output of the simulations suggest that tissue properties like growth anisotropy and proliferation rate (in the first case) and early- to latewood transition (in the second case) could be strongly linked to mechanical cell-autonomous properties and cell-cell interaction
Enzyme Replacement Therapy for FABRY Disease: Possible Strategies to Improve Its Efficacy
Enzyme replacement therapy is the only therapeutic option for Fabry patients with completely absent AGAL activity. However, the treatment has side effects, is costly, and requires conspicuous amounts of recombinant human protein (rh-AGAL). Thus, its optimization would benefit patients and welfare/health services (i.e., society at large). In this brief report, we describe preliminary results paving the way for two possible approaches: i. the combination of enzyme replacement therapy with pharmacological chaperones; and ii. the identification of AGAL interactors as possible therapeutic targets on which to act. We first showed that galactose, a low-affinity pharmacological chaperone, can prolong AGAL half-life in patient-derived cells treated with rh-AGAL. Then, we analyzed the interactomes of intracellular AGAL on patient-derived AGAL-defective fibroblasts treated with the two rh-AGALs approved for therapeutic purposes and compared the obtained interactomes to the one associated with endogenously produced AGAL (data available as PXD039168 on ProteomeXchange). Common interactors were aggregated and screened for sensitivity to known drugs. Such an interactor-drug list represents a starting point to deeply screen approved drugs and identify those that can affect (positively or negatively) enzyme replacement therapy
Rewiring and indirect effects underpin modularity reshuffling in a marine food web under environmental shifts
An Individual Based Model of Wound Closure in Plant Stems
Wound closure in plant stems (after either fire or mechanical damage) is a complex, multi-scale process that involves the formation of a callous tissue (callus lips) responsible for cell proliferation and overgrowth at the injury edges, resulting in coverage of the scarred tissue. Investigating such phenomena, it is difficult to discriminate between cell-specific growth responses, associated with physiological adaptations, and cell proliferation reactions emerging from specific cambium dynamics due to changes in mechanical constrains. In particular, the effects of cell–cell mechanical interactions on the wound closure process have never been investigated. To understand to what extent callus lip formation depends on the intra-tissue mechanical balance of forces, we built a simplified individual-based model (IBM) of cell division and differentiation in a generic woody tissue. Despite its simplified physiological assumptions, the model was capable to simulate callus hyperproliferation and wound healing as an emergent property of the mechanical interactions between individual cells. The model output suggests that the existence of a scar alone does constrain the growth trajectories of the remaining proliferating cells around the injury, thus resulting in the wound closure, ultimately engulfing the damaged tissue in the growing stem
Oxidoreductases and metal cofactors in the functioning of the earth
: Life sustains itself using energy generated by thermodynamic disequilibria, commonly existing as redox disequilibria. Metals are significant players in controlling redox reactions, as they are essential components of the engine that life uses to tap into the thermodynamic disequilibria necessary for metabolism. The number of proteins that evolved to catalyze redox reactions is extraordinary, as is the diversification level of metal cofactors and catalytic domain structures involved. Notwithstanding the importance of the topic, the relationship between metals and the redox reactions they are involved in has been poorly explored. This work reviews the structure and function of different prokaryotic organometallic-protein complexes, highlighting their pivotal role in controlling biogeochemistry. We focus on a specific subset of metal-containing oxidoreductases (EC1 or EC7.1), which are directly involved in biogeochemical cycles, i.e., at least one substrate or product is a small inorganic molecule that is or can be exchanged with the environment. Based on these inclusion criteria, we select and report 59 metalloenzymes, describing the organometallic structure of their active sites, the redox reactions in which they are involved, and their biogeochemical roles