Finding or Creating a Living Organism? Past and Future Thought Experiments in Astrobiology Applied to Artificial Intelligence.

This is a digest of how various researchers in biology and astrobiology have explored questions of what defines living organisms-definitions based on functions or structures observed in organisms, or on systems terms, or on mathematical conceptions like closure, chirality, quantum mechanics and thermodynamics, or on biosemiotics, or on Darwinian evolution-to clarify the field and make it easier for endeavors in artificial intelligence to make progress. Current ideas are described to promote work between astrobiologists and computer scientists, each concerned with living organisms. A four-parameter framework is presented as a scaffold that is later developed into what machines lack to be considered alive: systems, evolution, energy and consciousness, and includes Jagers operators and the idea of dual closure. A novel definition of consciousness is developed which describes mental objects both with and without communicable properties, and this helps to clarify how consciousness in machines may be studied as an emergent process related to choice functions in systems. A perspective on how quantization, acting on nucleic acids, sets up natural limits to system behavior is offered as a partial address to the problem of biogenesis.

Nonmedical Interventions for Schizophrenia: A Review of Diet, Exercise, and Social Roles.

Schizophrenia is a major mental illness with a disease course that is influenced by lifestyle. The risk-benefit ratio for alternative interventions is more favorable than for antipsychotics in long-term treatment. Dietary interventions may target autoimmune features, vitamin or mineral deficiencies, abnormal lipid metabolism, gluten sensitivity, or others. Examples of interventions involving diet, physical activity, or physical processes or social interventions including talk therapy exist in the literature. Notwithstanding, the general utility of these types of interventions remains inconclusive, awaiting long-term randomized trials. A perspective that separates the cause of the disease from its symptoms may be helpful in treatment planning and is warranted to distinguish between short-term and long-term recovery goals.

Novel membrane-bound reporter molecule for sorting high producer cells by flow cytometry.

We developed a membrane bound reporter and selection molecule for sorting by fluorescence activated cell sorting (FACS) of cells producing a protein of interest. This molecule is composed of a transmembrane (TM) domain, fused on its extracellular end to a biotin mimetic peptide (BMP) and on its intracellular side to puromycin N-acetyl transferase (PAC). In this format BMP is displayed on the cell membrane surface and PAC faces the cell cytoplasm. BMP was detected and quantified on the cell surface by fluorescently labelled streptavidin, allowing cell sorting by FACS, according to the reporter expression level. The reporter and a gene of interest (GOI) were connected on the same transcript via an internal ribosomal entry site (IRES). The reporter expression level was found to correlate with that of the GOI, enabling sorting of high producer cells by FACS. Thus, the highest fluorescent cells sorted had also the highest protein of interest (POI) productivity level.

Case Report: Psychiatric Symptoms Associated With the Moderna mRNA COVID-19 Vaccine Administration and Their Resolution.

This case report describes the sudden presentation and successful cessation of psychiatric symptoms following the first administration of the Moderna mRNA vaccine against the SARS-CoV-2 virus during early 2021. The process of discovery of symptoms is described, along with an empirical procedure which identified St. John's wort as the mediating agent. Implications for self-medication of mild depression are discussed. Hypericin, a constituent agent in St. John's wort, interacts with the SARS-CoV-2 spike protein. Sensitization to hypericin following vaccine administration is consistent with the observed symptoms.

Electrochemical cells from water ice? Preliminary methods and results.

Electrochemical cells from ice will be an important seasonal addition to power generation in cold regions. We demonstrate power generation on the order of 0.1 mW at 0.3 V and 0.13 m2 surface area using an electrochemical cell with 2% HCl providing a pH gradient in ice, and suggest a solar add-on effect due to temperature changes under direct sunlight. Different models are discussed, and data are presented related to different additives: (1) solutes such as NaCl and monopotassium phosphate; (2) pH modifying agents such as acids and bases; (3) particulate suspensions with kaolinite and other substances. The results are positive and suggest viable use of electrochemical cells from ice with low fabrication costs and safe environmental impact for ephemeral power generation, especially with future material improvements and refinement of technique. Current research in this nascent field is also briefly introduced. The model presented has implications both for power systems and for biology: an icy-worlds hypothesis for the origin of life suggests a protometabolism with an ice-based pH gradient.

Discordant antibody and cellular responses to Pneumocystis major surface glycoprotein variants in mice.

BACKGROUND: The major surface glycoprotein (Msg) of Pneumocystis is encoded by approximately 50 to 80 unique but related genes. Msg diversity may represent a mechanism for immune escape from host T cell responses. We examined splenic T cell proliferative and cytokine as well as serum antibody responses to recombinant and native Pneumocystis antigens in immunized or Pneumocystis-infected mice. In addition, immune responses were examined in 5 healthy humans. RESULTS: Proliferative responses to each of two recombinant Msg variant proteins were seen in mice immunized with either recombinant protein, but no proliferation to these antigens was seen in mice immunized with crude Pneumocystis antigens or in mice that had cleared infection, although the latter animals demonstrated proliferative responses to crude Pneumocystis antigens and native Msg. IL-17 and MCP-3 were produced in previously infected animals in response to the same antigens, but not to recombinant antigens. Antibody responses to the recombinant P. murina Msg variant proteins were seen in all groups of animals, demonstrating that all groups were exposed to and mounted immune responses to Msg. No human PBMC samples proliferated following stimulation with P. jirovecii Msg, while antibody responses were detected in sera from 4 of 5 samples. CONCLUSIONS: Cross-reactive antibody responses to Msg variants are common, while cross-reactive T cell responses are uncommon; these results support the hypothesis that Pneumocystis utilizes switching of Msg variant expression to avoid host T cell responses.

Lightning for Energy and Material Uses: A Structured Review.

The average atmospheric charge density of Earth is neutral. Charge built up from thunderstorms and lightning phenomena is offset by oceanic surface charging, and offers a source of energy that has not been harnessed broadly. Unfortunately, the total terrestrial energy of the Earth's atmospheric electrical system is modest (250-500 MW) compared to industrial requirements: Innovations are likely to offer improvements to societal efficiency rather than broad transformations. Direct capture systems located in places with very high occurrence of lightning discharge can generate ≈1 kWh per year on average. Material processing via triggered lightning is limited to techniques that utilize rapid discharges, e.g., metal and glass preprocessing of materials, waste volume reduction, biomass energy conversion, where current prices make plasma-arc processes prohibitive. Triggered lightning may be used to assist blasting of mountain rock; or as a high-voltage input for processes such as nuclear fusion. Passive collection of atmospheric electricity is modest but may be used in urban agriculture to increase biomass production. Thunderstorm charge-separation processes suggest a new class of electricity generators based on kinetic energy and material collision. Ball lightning suggests additional research in dusty plasmas. These methods are all at proof-of-concept or early translation stages.

Activated ALK collaborates with MYCN in neuroblastoma pathogenesis.

Amplification of the MYCN oncogene in childhood neuroblastoma is often accompanied by mutational activation of ALK (anaplastic lymphoma kinase), suggesting their pathogenic cooperation. We generated a transgenic zebrafish model of neuroblastoma in which MYCN-induced tumors arise from a subpopulation of neuroblasts that migrate into the adrenal medulla analog following organogenesis. Coexpression of activated ALK with MYCN in this model triples the disease penetrance and markedly accelerates tumor onset. MYCN overexpression induces adrenal sympathetic neuroblast hyperplasia, blocks chromaffin cell differentiation, and ultimately triggers a developmentally-timed apoptotic response in the hyperplastic sympathoadrenal cells. Coexpression of activated ALK with MYCN provides prosurvival signals that block this apoptotic response and allow continued expansion and oncogenic transformation of hyperplastic neuroblasts, thus promoting progression to neuroblastoma.

Dynamic movement of the calcium sensor STIM1 and the calcium channel Orai1 in activated T-cells: puncta and distal caps.

The proteins STIM1 and Orai1 are the long sought components of the store-operated channels required in T-cell activation. However, little is known about the interaction of these proteins in T-cells after engagement of the T-cell receptor. We found that T-cell receptor engagement caused STIM1 and Orai1 to colocalize in puncta near the site of stimulation and accumulate in a dense structure on the opposite side of the T-cell. FRET measurements showed a close interaction between STIM1 and Orai1 both in the puncta and in the dense cap-like structure. The formation of cap-like structures did not entail rearrangement of the entire endoplasmic reticulum. Cap formation depended on TCR engagement and tyrosine phosphorylation, but not on channel activity or Ca(2+) influx. These caps were very dynamic in T-cells activated by contact with superantigen pulsed B-cells and could move from the distal pole to an existing or a newly forming immunological synapse. One function of this cap may be to provide preassembled Ca(2+) channel components to existing and newly forming immunological synapses.