Lifeboat Foundation

New opinions are always suspected, and usually opposed, without any other reason but because they are not already common.” –John Locke.

This introductory article summarizes the tenets of the Cybernetic Theory of Mind (CTM) with the five foundational axioms. All of these starting assumptions for the new ontological framework are discussed in my recent book The Syntellect Hypothesis: Five Paradigms of the Mind’s Evolution. Here I try to keep this summary short and simple for the reader, maximally leaning towards a more literary, “bookish” style rather than the overly scholarly one. Also, The Cybernetic Theory of Mind is a working title for my upcoming book to be published sometime next year for the general audience. It may be followed by academic papers to clarify some thorny issues that I intend to publish on my own or in collaboration.

The CTM model, a proposed version of the theory of everything, I’m currently working on, is an integral multi-disciplinary ontological model that allows to draw a wide variety of predictions and deductions from the intersections of two or more foundational axioms therein. The CTM model also allows integration of further epistemic elements under its broad ontological umbrella as they come to be known. In this summary, the formulation of each foundational axiom is followed by five exemplary deductions per axiom.

Both genetic and non-genetic factors underlie the intratumoural heterogeneity that fuels cancer evolution. This Review discusses the application of single-cell multi-omics technologies to the study of cancer evolution, which capture and integrate the different layers of heritable information and reveal their complex interplay.

We now know that all extant living creatures derive from a single common ancestor, called the ‘Last Universal Common Ancestor’ (LUCA). It’s hard to think of a more unifying view of life. All living things are linked to a single-celled creature, the deepest root to the complex-branching tree of life. If we could play the movie of life backward, we would find this microscopic primogenitor at the starting point of biological evolution, the sole actor in what would become a very dramatic story, lasting some 3.5 billion years leading to us.

The answer is in their genes—especially those that encode for basic life functions, such as metabolism. Thanks to the lowly C. elegans worm, we’ve uncovered genes and molecular pathways, such as insulin-like growth factor 1 (IGF-1) signaling that extends healthy longevity in yeast, flies, and mice (and maybe us). Too nerdy? Those pathways also inspired massive scientific and popular interest in metformin, hormones, intermittent fasting, and even the ketogenic diet. To restate: worms have inspired the search for our own fountain of youth.

Still, that’s just one success story. How relevant, exactly, are those genes for humans? We’re rather a freak of nature. Our aging process extends for years, during which we experience a slew of age-related disorders. Diabetes. Heart disease. Dementia. Surprisingly, many of these don’t ever occur in worms and other animals. Something is obviously amiss.

In this month’s Nature Metabolism, a global team of scientists argued that it’s high time we turn from worm to human. The key to human longevity, they say, lies in the genes of centenarians. These individuals not only live over 100 years, they also rarely suffer from common age-related diseases. That is, they’re healthy up to their last minute. If evolution was a scientist, then centenarians, and the rest of us, are two experimental groups in action.

Graphene and other carbon materials are known to change their structure and even self-heal defects, but the processes involved in these atomic rearrangements often have high energy barriers and so shouldn’t occur under normal conditions. An international team of researchers in Korea, the UK, Japan, the US and France has now cleared up the mystery by showing that fast-moving carbon atoms catalyse many of the restructuring processes.

Graphene – a carbon sheet just one atomic layer thick – is an ideal system for studying defects because of its simple two-dimensional single-element structure. Until now, researchers typically explained the structural evolution of graphene defects via a mechanism known as a Stone-Thrower-Wales type bond rotation. This mechanism involves a change in the connectivity of atoms within the lattice, but it has a relatively large activation energy, making it “forbidden” without some form of assistance.

Using some of the best transmission electron microscopes available, researchers led by Alex Robertson of Oxford University and Kazu Suenaga of AIST Tsukuba found that so-called “mediator atoms” – carbon atoms that do not fit properly into the graphene lattice – act as catalysts to help bonds break and form. “The importance of these rapid, unseen ‘helpers’ has been previously underestimated because they move so fast and have been next-to-impossible to observe,” says co-team leader Christopher Ewels, a nanoscientist at the University of Nantes.

The advent of DNA sequencing has given scientists a clearer insight into the interconnectedness of evolution and the web-like path that different organisms take, splitting apart and coming back together. Tony Capra, associate professor of biological sciences, has come to new conclusions about the influence of Neanderthal DNA on some genetic traits of modern humans.

The article “Neanderthal introgression reintroduced functional ancestral alleles lost in Eurasian populations” was published in the journal Nature Ecology & Evolution on July 27.

The ancestors of all modern humans lived across the African continent, until approximately 100,000 years ago when a subset of humans decided to venture further afield. Neanderthals, an extinct relative of modern humans, had been longtime residents of Europe and central and south Asia; their ancestors had already migrated there 700,000 years previously. The humans who moved into central Asia and the Middle East encountered and reproduced with Neanderthals. Neanderthal DNA is present in some modern humans, and now research shows that can sometimes be a good thing.

Hundreds of thousands of years ago, our ancestors evolved a simple trick that could have helped thwart a major infectious disease. It probably saved our skins, but the change was far from a perfect solution.

New research has uncovered evidence that mutations arising between 600,000 and 2 million years ago were part of a complex of adaptations that may have inadvertently made us prone to inflammatory diseases and even other pathogens.

An international team of researchers compared around a thousand human genomes with a few from our extinct cousins, the Neanderthals and Denisovans, to fill in missing details on the evolution of a family of chemicals that coat the human body’s cells.

CRISPR-Cas9 base editors comprise RNA-guided Cas proteins fused to an enzyme that can deaminate a DNA nucleoside. No natural enzyme deaminates adenine in DNA, and so a breakthrough came when a natural transfer RNA deaminase was fused to Cas9 and evolved to give an adenine base editor (ABE) that works on DNA. Further evolution provided the enzyme ABE8e, which catalyzes deamination more than 1000 times faster than early ABEs. Lapinaite et al. now present a 3.2-angstrom resolution structure of ABE8e bound to DNA in which the target adenine is replaced with an analog designed to trap the catalytic conformation. The structure, together with kinetic data comparing ABE8e to earlier ABEs, explains how ABE8e edits DNA bases and could inform future base-editor design.

Science, this issue p. 566

CRISPR-Cas–guided base editors convert A•T to G•C, or C•G to T•A, in cellular DNA for precision genome editing. To understand the molecular basis for DNA adenosine deamination by adenine base editors (ABEs), we determined a 3.2-angstrom resolution cryo–electron microscopy structure of ABE8e in a substrate-bound state in which the deaminase domain engages DNA exposed within the CRISPR-Cas9 R-loop complex. Kinetic and structural data suggest that ABE8e catalyzes DNA deamination up to ~1100-fold faster than earlier ABEs because of mutations that stabilize DNA substrates in a constrained, transfer RNA–like conformation. Furthermore, ABE8e’s accelerated DNA deamination suggests a previously unobserved transient DNA melting that may occur during double-stranded DNA surveillance by CRISPR-Cas9. These results explain ABE8e-mediated base-editing outcomes and inform the future design of base editors.

Crop yields for apples, cherries and blueberries across the United States are being reduced by a lack of pollinators, according to Rutgers-led research, the most comprehensive study of its kind to date.

Most of the world’s crops depend on honeybees and wild bees for pollination, so declines in both managed and wild bee populations raise concerns about food security, notes the study in the journal Proceedings of the Royal Society B: Biological Sciences.

“We found that many crops are pollination-limited, meaning crop production would be higher if crop flowers received more pollination. We also found that honey bees and wild bees provided similar amounts of pollination overall,” said senior author Rachael Winfree, a professor in the Department of Ecology, Evolution, and Natural Resources in the School of Environmental and Biological Sciences at Rutgers University-New Brunswick. “Managing habitat for native bee species and/or stocking more honey bees would boost pollination levels and could increase crop production.”