On biological individuation.

In this paper, we understand the emergence of life as a pure individuation process. Individuation already occurs in open thermodynamics systems near equilibrium. We understand such open systems, as already recursively characterized (R1) by the relation between their internal properties, and their boundary conditions. Second, global properties emerge in such physical systems. We interpret this change as the fact that their structure is the recursive result of their operations (R2). We propose a simulation of the emergence of life in Earth by a mapping (R) through which (R1R2) operators are applied to themselves, so that RN = (R1R2)N. We suggest that under specific thermodynamic (open systems out of equilibrium) and chemical conditions (autocatalysis, kinetic dynamic stability), this mapping can go up to a limit characterized by a fixed-point equation: [Formula: see text]. In this equation, ([Formula: see text]) symbolizes a regime of permanent resonance characterizing the biosphere, as open from inside, by the recursive differential relation between the biosphere and all its holobionts. As such the biosphere is closed on itself as a pure differential entity. ([Formula: see text]) symbolizes the regime of permanent change characterizing the emergence of evolution in the biosphere. As such the biosphere is closed on itself, by the principle of descent with modifications, and by the fact that every holobiont evolves in a niche, while evolving with it.

Potential Treatment of Lysosomal Storage Disease through Modulation of the Mitochondrial-Lysosomal Axis.

Lysosomal storage disease (LSD) is an inherited metabolic disorder caused by enzyme deficiency in lysosomes. Some treatments for LSD can slow progression, but there are no effective treatments to restore the pathological phenotype to normal levels. Lysosomes and mitochondria interact with each other, and this crosstalk plays a role in the maintenance of cellular homeostasis. Deficiency of lysosome enzymes in LSD impairs the turnover of mitochondrial defects, leading to deterioration of the mitochondrial respiratory chain (MRC). Cells with MRC impairment are associated with reduced lysosomal calcium homeostasis, resulting in impaired autophagic and endolysosomal function. This malicious feedback loop between lysosomes and mitochondria exacerbates LSD. In this review, we assess the interactions between mitochondria and lysosomes and propose the mitochondrial-lysosomal axis as a research target to treat LSD. The importance of the mitochondrial-lysosomal axis has been systematically characterized in several studies, suggesting that proper regulation of this axis represents an important investigative guide for the development of therapeutics for LSD. Therefore, studying the mitochondrial-lysosomal axis will not only add knowledge of the essential physiological processes of LSD, but also provide new strategies for treatment of LSD.

ATM mediated-p53 signaling pathway forms a novel axis for senescence control.

Previously, we uncovered a novel mechanism in which senescence is controlled by mitochondrial functional recovery upon Ataxia-telangiectasia mutated (ATM) inhibition. However, it remains elusive how ATM controls signaling pathways to achieve restorative effect. In this study, we performed microarray and found that p53 pathway was differentially expressed upon ATM inhibition. We found that ATM inhibition yields senescence amelioration through p53-dependent manner. The restorative effect was also afforded by direct p53 inhibition. Furthermore, mitochondrial metabolic reprogramming via p53 inhibition was a prerequisite for senescence amelioration. Taken together, our data indicated that p53 pathway functions as potential target for ATM-mediated senescence amelioration.

From physical to biological individuation.

In this paper, we insist on stressing the epistemic and metaphysical difference between individual and individuation, a distinction originally developed by Gilbert Simondon. Individuation occurs in complex physical systems by the coupling (R1) between the system and its outside conditions. As such the system is not well defined by its sole constituents. Let's characterize (R2) as follows: the system is not entirely defined by its structure at a given time because this structure will change and global emergent properties will appear, as in the paradigmatic example of phase transition. Thus physical individuation is defined both by the coupling of a physical system with its environment (R1) and by its diachronic dynamics taking place (R2). We interpret biological individuation as a second order one, i.e. as a recursive procedure through which physical individuation is also acting on "its own theatre". We represent this procedure like a mapping through which (R1R2) are applied to themselves, so that: RN = (R1R2)N. We highlight the relation between this assumption and the concept of extended criticality developed by Bailly, Longo and Montévil.