for - Micheal Levin - developmental biology - evolutionary biology - cellular intelligence

for - Rainbow body - Deep Humanity - superorganism - multi-level communication - adjacency between - contemplative practice - direct experience of body's cellular activity

summary - Father Tiso and his catholic lineage combined with scholarship in Tibetan studies places him in a unique position for interfaith dialogue - His research interest in investigating the extraordinary and unexplained Tibetan meditation phenomena of Rainbow Body manifested by the greatest practitioners at the time of death (including contemporary ones) sheds light on the Rainbow Body phenomena in many spiritual traditions and challenges the scientific community to come up with an explanation for it. - If scientifically proven true, it offers an extraordinary possibility of human potential - Contemplation could be the practice technique that could directly bridge normal human consciousness with the microscopic world around us, which to date, is only accessible through scientific instrumentation.

question - Does deep contemplative practice offers a direct access to the microscopic reality? - If so, how does it accomplish this direct communication with human cells, and indeed, even the universe itself? - Father Tiso shares centuries old recorded visual drawings of experiences reported by Rainbow Body practitioners and speculates whether these drawings represent direct experience of the cellular scale of our human form - Indeed, could it even be at the quantum level of experience, since rainbows are an optical phenomenal?

for - evolution - multicellular - MuLTEE

• for: cellular collaboration, gap junction, bioelectrical networks, bioelectric network

• interesting fact: multicellular mechanisms to create coherence in competent constituent subunit cells

• more research
  • very interesting mechanisms that mediate benefits of collective behavior of competent subunits within the biological body.

Review coordinated by Life Science Editors Foundation

Reviewed by: Dr. Angela Andersen, Life Science Editors Foundation

Potential Conflicts of Interest: None

Punch line: Activation of the yeast AMP-activated protein kinase (AMPK) negatively regulates MAGIC, inhibits the import of misfolded proteins into mitochondria & promotes mitochondrial biogenesis and fitness.

Why is this interesting? Maybe all those healthy things like caloric restriction, intermittent fasting, exercise etc that activate AMPK & extend lifespan do so by inhibiting MAGIC & preventing mitochondrial damage from misfolded proteins.

Background: Metabolic imbalance & loss of proteostasis are interconnected hallmarks of aging and age-related diseases. A mitochondria-mediated proteostasis mechanism called MAGIC (mitochondria as guardian in cytosol) concentrates cytosolic misfolded protein at the surface of mitochondria, where they are disaggregated by molecular chaperones, and then imported for degradation by mitochondrial proteases. Inhibition of this pathway prolongs protein aggregation in cytosol after proteotoxic stress, but excessive misfolded proteins in mitochondria can lead to mitochondrial damage.

Results: • Genetic screen for MAGIC regulators uncovered 145 genes. Loss of Snf1 (AMPK homolog) led to increased mitochondrial import even without proteotoxic stress. In contrast indirect, constitutive activation of Snf1 (e.g. low glucose) prevented the import of misfolded proteins in mitochondria.

• The data suggest that the reduced accumulation of misfolded proteins in mitochondria of Snf1-active cells is not due to enhanced intramitochondrial degradation nor to reduced levels of the misfolded protein, but rather due to blocked mitochondrial import.

• Deletion of HAP4 counteracted Snf1 activation and overexpression of Hap4 alone recapitulated Snf1 activation. The Hap2/3/4/5 complex activates the expression of nuclear encoded mitochondrial proteins. Their data suggest that high expression of mitochondrial preproteins due to an elevated Snf1-Hap4 axis compete with misfolded proteins for mitochondrial import.

• Proteotoxic stress led to a reduced growth rate & reduced mitochondrial fitness in high glucose medium but not under glucose limitation. The data suggest that low glucose, activation of Snf1 & prevention of misfolded protein import into mitochondria prevent the growth defect.

• Many neurodegenerative disease-associated aggregation-prone proteins (α-synuclein, FUSP525L, TDP-43, amyloid beta, C9ORF72-associated poly(GR) dipeptide) are detected in mitochondria of human patients or disease models and impair mitochondrial functions. Their data suggest that the import of α-synuclein & associated reduction in mitochondrial fitness can be counteracted by indirect AMPK/Snf1 activation (i.e. glucose limitation).

• Show data in yeast & human cells.

Discussion: This paper revealed an unexpected link between cellular metabolism and proteostasis through MAGIC/mitochondria.

• Snf1/AMPK is a key regulator of MAGIC & of misfolded protein import into mitochondria.

• Snf1/AMPK balances the mitochondrial metabolic and proteostatic functions in response to glucose availability and protects mitochondrial fitness under proteotoxic stress.

• The authors speculate that in high glucose, cells rely on glycolysis for ATP production and mitochondria ‘moonlighting’ in cellular proteostasis through MAGIC, but when glucose is limited and cells rely on oxidative phosphorylation for ATP generation, AMPK is activated and shuts down MAGIC, prioritizing the import of essential mitochondrial preproteins to ensure mitochondrial fitness and energy production.

• Acknowledge limitations: Snf1/Hap4 activation elevates the expression of hundreds of mitochondrial preproteins, not clear whether specific preproteins or cytosolic factors directly involved in inhibiting mitochondrial import, & that more details on mechanisms will be of interest.

• Caloric restriction & AMPK activation might contribute to lifespan extension by inhibiting MAGIC. In human, AMPK activity is elevated during health-benefitting activities such as exercise. Their data suggest that elevating AMPK activity may be beneficial in alleviating proteotoxicity associated with degenerative diseases - but hyperactivated AMPK has also been reported in several neurodegenerative diseases with proteostasis decline (Ang wonders- maybe AMPK is overwhelmed?).

THIS IS A GORGEOUS PAPER!

Future work - I can't wait to see the characterization of the ribosome biogenesis genes that they also pulled out as MAGIC regulators. Anticipating a translation, misfolded protein, mitochondria, aging axis :)

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This is the key to Major Evolutionary Transition - a population of free living individual creatures discover that in teaming up, there is a greater resultant evolutionary fitness, mutualism symbiotic relationship emerges. It becomes so strong over time that the many become a self-replicating one.

The biological self is always defined by a boundary between inner and outer, but in this act of mutualism, the many biological selves join to form a new higher order biological self.

In this way, a multi-cellular species like ours is somewhat like one of those nested Russian dolls.

Indeed, Amanda Robins hypothesizes

https://hyp.is/NyrixELGEeyYWN_d76UNMg/docdrop.org/video/6J-J72GoqhY/

that our species has undergone what she and Peter Nonacs calls Major System Transition (MST). The cultural artifact of inscribed language has made possible a superorganism / supraorganism that has spread across the globe.

This is a great vid for showing how we are a multi-level being. Within this human body, we embed 4 different stages of Major Evolutionary Transitions (MET).

Our human body is the product of billions of years of evolution, embodying various outputs from each major stage of a Major Evolutionary Transition (MET). We are a multi-cellular being, a colony. Yet,at the same time, we have living elements that at one time in history, were independent living beings which were NOT part of a multi-cellular colony!

We have genes, that were once autonomous living entities, mitochondria within cells, which at one time were autonomous entities, and cells, which were also once autonomously existent eukaryotes. All three exist in transmuted form that is now integrated into our body.

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ATP better known as Adenosine triphosphate is an energy carrying molecule found in all living things cells. ATP takes the chemical energy from the process of breaking down food molecules to releases it as fuel for cellular processes.

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Hmm? I assumed 4G was lower range than 3G. From what I read here, 4G can work at a longer range, with lower capacity, scenarios and work at shorter range, high capacity scenarios.

But only if the cell phone provider has both low frequencies and high frequencies