This is a ~57 minute talk titled “The Bioelectric Interface to the Collective Intelligence of Morphogenesis: development, regeneration, cancer, and beyond” which I gave at a UCSF seminar for an audience of graduate students and post-docs in Biophysics, Bioinformatics, and Chemical Biology. I covered the role of bioelectricity as cognitive glue underlying high-level adaptive plasticity in living tissue, recent progress in exploiting that interface, and new developments in research platforms for this field.
Category: neuroscience – Page 13
Michael Levin: Novel Embodiments of Mind: Natural, Bioengineered, and Hybrid Interfaces
This is an invited talk in BAMΞ’s Mathematical Phenomenology Sprint.
Cf. https://bamxi.org/research-activities/mathematical-phenomenology-sprint/
Organizing Institutions:
Bamberg Mathematical Consciousness Science Initiative (BAMΞ) https://bamxi.org.
& Association for Mathematical Consciousness Science (AMCS) https://amcs-community.org
Controlled ‘oxidative spark’ may serve as a surprising ally in brain repair
Oxidative stress is a direct consequence of an excess in the body of so-called free radicals—reactive, unstable molecules that contain oxygen. Free radicals are normal metabolic by-products and also help to relay signals in the body. In turn, oxidative stress (an overload of these molecules) can be caused by lifestyle, environmental, and biological factors such as smoking, high alcohol consumption, poor diet, stress, pollution, radiation, industrial chemicals, and chronic inflammation.
When this occurs, it creates an imbalance between the production of free radicals and the body’s antioxidant defenses, which are responsible for neutralizing them.
The brain on books: How reading reshapes language processing
Learning to read reshapes how the brain processes language. New research from Baycrest and the University of São Paulo shows that learning to read fundamentally changes how the brain responds to spoken language, even when no written words are present. While previous brain imaging studies have demonstrated that literacy strongly affects how the brain responds to written words, this study is among the first to show differences in brain activity during listening alone.
The findings confirm that as people learn to read, they develop a skill known as phonemic awareness, the ability to hear and manipulate the individual sounds that make up spoken words, a core foundation of reading. The study shows that learning to read improves how the brain processes spoken language by increasing sensitivity to these component sounds. This, in turn, strengthens short-term verbal memory, supporting the ability to learn complex skills and manage the cognitive demands of daily life.
The work is published in the journal Cortex.
The role of the Cer1 transposon in horizontal transfer of transgenerational memory
Could a hybrid biohardware using neural orgamoids and silicon make minduploading easier.
Animals face both external and internal dangers: pathogens threaten from the environment, and unstable genomic elements threaten from within. C. elegans protects itself from pathogens by “reading” bacterial small RNAs, using this information to both induce avoidance and transmit memories for four generations. Here, we found that memories can be transferred from either lysed animals or from conditioned media to naive animals via Cer1 retrotransposon-encoded virus-like particles. Moreover, Cer1 functions internally at the step of transmission of information from the germline to neurons and is required for learned avoidance. The presence of the Cer1 retrotransposon in wild C. elegans strains correlates with the ability to learn and inherit small-RNA-induced pathogen avoidance. Together, these results suggest that C.
Multi-omic analysis of guided and unguided forebrain organoids reveals differences in cellular composition and metabolic profiles
The differences in guided and unguided forebrain organoids.
The differences arising from guided or unguided differentiation of human forebrain organoids is not well understood.
The researchers perform a multiomic analysis of forebrain organoids generated by these two key methods.
The researchers demonstrate that guided forebrain organoids contained a larger proportion of neurons, including GABAergic interneurons, whereas the unguided organoids contained significantly more choroid plexus, radial glia, and astrocytes at later stages.
They also show increased levels of oxidative phosphorylation and fatty acid β-oxidation in the unguided forebrain organoids and a higher reliance on glycolysis in the guided forebrain organoids. sciencenewshighlights ScienceMission https://sciencemission.com/guided-and-unguided-forebrain-organoids
Øhlenschlæger et al. perform a multi-omic analysis of forebrain organoids generated by two key methods, guided and unguided differentiation. They document significant differences in the cell type composition and metabolic profiles of the two forebrain organoid types, providing a resource and methodological guide for the neural organoid field.
Tumor-derived aminopeptidase N promotes early stages of brain metastatic colonization
In this study, we identified the aminopeptidase CD13 as a key mediator in a subset of human BrMs originating from breast and lung cancers, with approximately 30% of samples exhibiting cancer cell-specific CD13 expression. Notably, this prevalence aligns with previous reports in breast and lung primary tumors. In BC, CD13 cancer cell expression was documented in 36% of patient samples analyzed, with higher rates in invasive ductal carcinoma,31 while in lung cancer, 35% of patients analyzed were positive for cancer cell CD13 expression.32 These observations suggest that CD13 expression is maintained during metastatic progression to the brain, underscoring its potential as a therapeutic target. Importantly, CD13 expression in primary lung cancer is associated with significantly reduced survival, with a similar trend in BC.31,32 Consistent with these data, we show here that patients with HER2+ BC with CD13high tumors have significantly poorer clinical outcomes. These findings emphasize the importance of stratifying patients by CD13 status to better assess both its prognostic significance and therapeutic potential.
To gain mechanistic insight into CD13 function, we employed murine BrM models from three primary origins (breast, lung, and melanoma) that recapitulate distinct stages of the metastatic cascade. Notably, only the breast-BrM model exhibited robust CD13 expression, suggesting that lung cancer and melanoma may rely on alternative, CD13-independent mechanisms to colonize the brain. CD13 knockdown in breast-BrM cells significantly prolonged survival and reduced metastatic seeding following intracardiac injection. This effect was less pronounced when cancer cells were introduced directly into the brain parenchyma (intracranial injection) or implanted at the primary site (MFP), underscoring CD13’s predominant role during the initial colonization phase of metastasis.
Both gain-and loss-of-function experiments confirmed CD13’s functional importance in metastatic seeding. CD13 has been described as a moonlighting enzyme with diverse cellular functions relevant to regulating metastasis,16,17 including β1 integrin recycling,21 cell migration,21 and activation of the MAPK and PI3K pathways.33 Based on our RNA-seq analysis, CD13 overexpression may further enhance metastatic efficiency through activation of Rho family GTPases and effectors that orchestrate cytoskeletal remodeling, endothelial cell adhesion, and transendothelial migration.34 These features position CD13 as a compelling anti-cancer target; indeed, CD13 inhibition has been explored in several therapeutic development efforts. However, no brain-permeable CD13 inhibitor has yet been approved worldwide for clinical use,16 representing a critical gap in the translational landscape.
