Robust monomer-distribution biosignatures in evolving digital biota

Because organisms synthesize component molecules at rates that reflect those molecules' adaptive utility, we expect a population of biota to leave a distinctive chemical signature on their environment that is anomalous given the local (abiotic) chemistry. We observe the same effect in the distribution of computer instructions used by an evolving population of digital organisms, and characterize the robustness of the evolved signature with respect to a number of different changes in the system's physics. The observed instruction abundance anomaly has features that are consistent over a large number of evolutionary trials and alterations in system parameters, which makes it a candidate for a non-Earth-centric life-diagnosticComment: 22 pages, 4 figures, 1 table. Supplementary Material available from C

Monomer abundance distribution patterns as a universal biosignature: Examples from terrestrial and digital life

Organisms leave a distinctive chemical signature in their environment because they synthesize those molecules that maximize their fitness. As a result, the relative concentrations of related chemical monomers in life-bearing environmental samples reflect, in part, those compounds' adaptive utility. In contrast, rates of molecular synthesis in a lifeless environment are dictated by reaction kinetics and thermodynamics, so concentrations of related monomers in abiotic samples tend to exhibit specific patterns dominated by small, easily formed, low-formation-energy molecules. We contend that this distinction can serve as a universal biosignature: the measurement of chemical concentration ratios that belie formation kinetics or equilibrium thermodynamics indicates the likely presence of life. We explore the features of this biosignature as observed in amino acids and carboxylic acids, using published data from numerous studies of terrestrial sediments, abiotic (spark, UV, and high-energy proton) synthesis experments, and meteorite bodies. We then compare these data to the results of experimental studies of an evolving digital life system. We observe the robust and repeatable evolution of an analogous biosignature in a digital lifeform, suggesting that evolutionary selection necessarily constrains organism composition and that the monomer abundance biosignature phenomenon is universal to evolved biosystems.Comment: 35 pages, 5 figures. Supplementary material (two movie files) available upon request. To appear in J. Mol. Evo

Triggers, Timescales, and Treatments for Cytokine-Mediated Tissue Damage

Inflammation is an essential cytokine-mediated process for generating a neutralizing immune response against pathogens and is generally protective. However, aberrant or excessive production of pro-inflammatory cytokines is associated with uncontrolled local and systemic inflammation, resulting in cell death and often irreversible tissue damage. Uncontrolled inflammation can manifest over timescales spanning hours to years and is primarily dependent on the triggering event. Rapid and potentially lethal increase in cytokine production, or a 'cytokine storm,' develops in hours to days and is associated with cancer cell-based immunotherapies, such as CAR-T cell therapy. On the other hand, some bacterial and viral infections with high microbial replication or highly potent antigens elicit immune responses that result in supraphysiological systemic cytokine concentrations which manifest over days to weeks. Immune dysregulation in autoimmune diseases can lead to chronic cytokine-mediated tissue damage spanning months to years, which often occurs episodically. While the initiating events and cellular participants may differ in these disease processes, many of the cytokines that drive disease progression are shared. For example, upregulation of IL-1, IL-6, IFN-γ, TNF, and GM-CSF frequently coincides with cytokine storm, sepsis, and autoimmune disease. Targeted inhibition of these pro-inflammatory molecules via antagonist monoclonal antibodies has improved clinical outcomes, but the complexity of the underlying immune dysregulation results in high variability. Rather than a "one size fits all" treatment approach, an identification of disease endotypes may permit the development of effective therapeutic strategies that address the contributors of disease progression. Here, we present a literature review of the cytokine-associated etiology of acute and chronic cytokine-mediated tissue damage, describe successes and challenges in developing clinical treatments, and highlight advancements in preclinical therapeutic strategies for mitigating pathological cytokine production