Aims to enumerate novel life science paradigms and theories. In the beginning of the twentieth century Lord Kelvin (may have) famously declared: 'There is nothing new to be discovered in physics now, All that remains is more and more precise measurement' That was before relativity and quantum mechanics. We thought the human genome project would unlock the workings of our bodies save a few details. Let's not make the same mistake twice. Let's explore with maniacal curiosity and critical reasoning until, truly, all that's left is refined measurement and engineering.
"Increasing evidence indicates that the post-translationally modified histones serve as extremely selective binding platforms for specific regulatory proteins that drive distinct nuclear processes.
It has been known for over 45 years now that histones can be post-translationally modified by specific enzymes that ‘write?a histone code by adding or removing a number of different chemical modifications, including acetyl, phosphoryl and methyl groups (Figure 2). Since these modifications occur only on specific amino acid residues on specific histones in various eukaryotic organisms, these observations strongly linked the modifications?involvement in nuclear processes. For example, the acetylation of key lysine residues of histone H3 and H4 by enzymes known as histone acetyltransferases (HATs) was known to play a pivotal role in transcriptional activation."
"Fertile queens and sterile workers are alternative forms of the adult female honeybee that develop from genetically identical larvae following differential feeding with royal jelly. We show that silencing the expression of DNA methyltransferase Dnmt3, a key driver of epigenetic global reprogramming, in newly hatched larvae led to a royal jelly–like effect on the larval developmental trajectory; the majority of Dnmt3 small interfering RNA–treated individuals emerged as queens with fully developed ovaries. Our results suggest that DNA methylation in Apis is used for storing epigenetic information, that the use of that information can be differentially altered by nutritional input, and that the flexibility of epigenetic modifications underpins, profound shifts in developmental fates, with massive implications for reproductive and behavioral status."
Colbert Sesanker's insight:
The bee colony is genetically identical, but Queens are made when workers feed larva 'Royal Jelly' for an extended period of time. Queens exhibit vastly different gene expression patterns from workers. This is caused by epigenetic modifications.
The queen differentiation program was replicated by blocking (using small siRNA to silence methyltransferase Dnmt3) CpG methylation in larva.
"Scientists were shocked to learn that about 90 percent of the fibers in the primary visceral nerve, the vagus, carry information from the gut to the brain and not the other way around."
"The enteric nervous system uses more than 30 neurotransmitters, just like the brain, and in fact 95 percent of the body's serotonin is found in the bowels."
Colbert Sesanker's insight:
Was there any scientific reason to assume there was not a significant gut brain link?
"The second brain doesn't help with the great thought processes…religion, philosophy and poetry is left to the brain in the head," says Michael Gershon, chairman of the Department of Anatomy and Cell Biology at New York–Presbyterian Hospital/Columbia University Medical Center, an expert in the nascent field of neurogastroenterology and author of the 1998 book The Second Brain"
Somehow he 'knows' the gut 'doesn't help' with higher order cognitive reasoning. How does he authoritatively know this? Even if the gut served as a switch to initiate different cognitive programs, that would certainly constitute 'help' and seems plausible. Indeed, if there is feedback between the gut and higher order cognition, one would have to accept the gut is part of the system mediating the higher order cognition.
"Why We Should Stop Using Brain Metaphors When We Talk About Computing.
Spectrum: It’s always been my impression that when people in computer science describe how the brain works, they are making horribly reductionist statements that you would never hear from neuroscientists. You called these “cartoon models” of the brain.
Michael Jordan: I wouldn't want to put labels on people and say that all computer scientists work one way, or all neuroscientists work another way. But it’s true that with neuroscience, it’s going to require decades or even hundreds of years to understand the deep principles. There is progress at the very lowest levels of neuroscience. But for issues of higher cognition—how we perceive, how we remember, how we act—we have no idea how neurons are storing information, how they are computing, what the rules are, what the algorithms are, what the representations are, and the like. So we are not yet in an era in which we can be using an understanding of the brain to guide us in the construction of intelligent systems."
Colbert Sesanker's insight:
finally someone calls out the lost that think the brain is one giant deep neural network or (gasp) a hierarchical hidden markov model (kurzweil in 'How to Build a Mind')
"Your genome is the same right now as it was yesterday, last week, last year, or the day you were born. But your microbiomes—the combined genes of all the trillions of microbes that share your body—have shifted since the sun came up this morning. And they will change again before the next sunrise.
Christoph Thaiss from the Weizmann Institute of Science has discovered that the communities of microbes in out guts vary on a daily cycle. Some species rise to the fore during daylight hours and recede into the background at night, while others show the opposite pattern.
These cycles are a lot like our own body clocks, or circadian rhythms. Over a 24 hour period, the levels of many molecules in our body rise and fall in predictable fashion. These rhythms affect everything from our body temperature to our brain activity to how well we respond to medicine. But these clocks tick by themselves. You can reset them by exposing yourself to light at different times of day (which is what we do when we cross time zones and get jetlag), but they are still self-sustaining.
Our microbiome clock is not. The microbes aren’t waxing and waning of their own accord. Their world is completely dark. There’s no way for them to tell what time of the day it is, except for clues provided by us. The most important of these clues is food. Thanks to our own rhythms, we eat at regular times of the day, and it’s these feeding patterns that drive the cycles in our microbiome. Diet is the gear that synchronises the ticks of our clocks with those of our microbes."
The Western Ghats in India rise like a wall between the Arabian Sea and the heart of the subcontinent to the east. The 1,000-mile-long chain of coastal mountains is dense with lush rainforest and grasslands, and each year, clouds bearing monsoon rains blow in from the southwest and break against the mountains’ flanks, unloading water that helps make them hospitable to numerous spectacular and endangered species. The Western Ghats are one of the most biodiverse places on the planet. They were also the first testing ground of an unusual new theory in ecology that applies insights from physics to the study of the environment.
"My research focuses on applying information theory and complexity science to genomics, synthetic and network biology. With backgrounds in math, computer science and philosophy, I think of myself as a kind ofexperimental philosopher or a computational natural scientist. (Greg Chaitin once referred to me as a "new kind of practical theoretician")."
"Konrad Zuse (1910-1995; pronounce: "Conrud Tsoosay") not only built the first programmable computers (1935-1941) and devised the first higher-level programming language (1945), but also was the first to suggest (in 1967) that the entire universe is being computed on a computer, possibly a cellular automaton (CA). He referred to this as "Rechnender Raum" or Computing Space or Computing Cosmos. Many years later similar ideas were also published / popularized / extended by Edward Fredkin (1980s), Jürgen Schmidhuber (1990s - see overview), and more recently Stephen Wolfram (2002) (see comments and Edwin Clark's review page ). Zuse's first paper on digital physics and CA-based universes was:
Zuse is careful: on page 337 he writes that at the moment we do not have full digital models of physics, but that does not prevent him from asking right there: which would be the consequences of a total discretization of all natural laws? For lack of a complete automata-theoretic description of the universe he continues by studying several simplified models. He discusses neighbouring cells that update their values based on surrounding cells, implementing the spread and creation and annihilation of elementary particles. On page 341 he writes "In all these cases we are dealing with automata types known by the name "cellular automata" in the literature" and cites von Neumann's 1966 book: Theory of self-reproducing automata. On page 342 he briefly discusses the compatibility of relativity theory and CAs."
Leiner, Leiner, and Dow proposed that the co-evolution of cerebral cortex and the cerebellum over the last million years gave rise to the unique cognitive capacities and language of humans. Following the findings of recent imaging studies by Imamizu and his colleagues, it is proposed that over the last million or so years language evolved from the blending of (1) decomposed/re-composed contexts or “moments” of visual-spatial experience with (2) those of sound patterns decomposed/re-composed from parallel context-appropriate vocalizations (calls or previously acquired “words”). It is further proposed that the adaptive value of this blending was the progressively rapid access to the control of detailed cause-and-effect relationships in working memory as it entered new and challenging environments. Employing the complex syntactical sequence of nut-cracking among capuchin monkeys, it is proposed how cerebro-cerebellar blending of low-volume vocalization and visual-spatial working memory could have produced the beginnings of the phonological loop as proposed by Baddeley, Gathercole, and Papagno. It is concluded that the blending of cerebellar internal models in the cerebral cortex can explain the evolution of human advancements in the manipulation of cause-and-effect ideas in working memory, and, therefore, the emergence of the distinctive “cognitive niche” of humans proposed by Tooby and DeVore and supportively elaborated by Pinker.
"The study of neuropsychology traditionally begins with geography: the neocortex as the seat of cognition and behavior, and the subcortical regions coordinating movement. Subcortical Structures and Cognition breaks with this traditional view, arguing for a practice-oriented rethinking of brain organization"
Colbert Sesanker's insight:
The sections on the cerebellum are very good. Again, was there any scientific reason to assume subcortical structures are not involved in higher order cognition? Nope. Dr. Rhawn Joseph, an idea machine, demonized for a handful of silly things he said, has been saying this for a while.
"Primates recognize objects in natural visual scenes with great rapidity. The ventral visual cortex is usually assumed to play a major role in this ability (“high-road”). However, the “low-road” alternative frequently proposed is that the visual cortex is bypassed by a rapid subcortical route to the amygdala, especially in the case of biologically relevant and emotional stimuli. This paper highlights the lack of evidence from psychophysics and computational models to support this “low-road” alternative. Most importantly, the timing of neural responses invites a serious reconsideration of the low-road role in rapid processing of visual objects."
Colbert Sesanker's insight:
subcortical processing of visual information? maybe not.
Transfer entropy is a recently introduced information-theoretic measure quantifying directed statistical coherence between spatiotemporal processes, and is widely used in diverse fields ranging from finance to neuroscience. However, its relationships to fundamental limits of computation, such as Landauer's limit, remain unknown. Here we show that in order to increase transfer entropy (predictability) by one bit, heat flow must match or exceed Landauer's limit. Importantly, we generalise Landauer's limit to bi-directional information dynamics for non-equilibrium processes, revealing that the limit applies to prediction, in addition to retrodiction (information erasure). Furthermore, the results are related to negentropy, and to Bremermann's limit and the Bekenstein bound, producing, perhaps surprisingly, lower bounds on the computational deceleration and information loss incurred during an increase in predictability about the process. The identified relationships set new computational limits in terms of fundamental physical quantities, and establish transfer entropy as a central measure connecting information theory, thermodynamics and theory of computation.
"Keith Porter culminated his stellar career as the founding father of biological electron microscopy by acquiring, in the late 1970s, a high-voltage electron microscope (HVEM). With this magnificent instrument he examined whole-mounts of cultured cells, and perceived within them a structured cytoplasmic matrix he named the “microtrabecular lattice”. Over the next decade Porter published a series of studies, together with a team of outstanding young colleagues, which elaborated his broader “microtrabecular concept.” This concept posited that microtrabeculae were real physical entities that represented the fundamental organization the cytoplasm, and that they were the physical basis of cytoplasmic motility and of cell-shape determination. The present review presents Porter’s original images of microtrabeculae, after conversion to a more interpretable “digital-anaglyph” form, and discusses the rise and fall of the microtrabecular concept. Further, it explains how the HVEM images of microtrabeculae finally came to be considered as an artifact of the preparative methods Porter used to prepare whole cells for HVEM. Still, Keith’s “microtrabecular concept” foretold of our current appreciation of the complexity and pervasiveness of the cytoskeleton, which has now been found by more modern methods of EM to actually be the fundamental organizing principle of the cytoplasmic matrix. During the impending eclipse of Porter’s microtrabecular concept in the late 1980s, many of Keith’s colleagues fondly described the cell as being filled, not with protoplasm, but with “Porterplasm.” Despite the fact that Keith’s view was clouded by the methods of his time, it would be fitting and apt to retain this name, still today, for the ordered matrix of cytoskeletal macromolecules that exists in the living cell. In the end, the story of what happened to Porter’s microtrabecular concept should be an object lesson in scientific hubris that should humble and inform all of us in cell biology, even today – particularly when we begin to think that our most recent methods and observations are achieving “the last word”."
Colbert Sesanker's insight:
frohlich proposed this lattice as the substrate of energy transfer for coherent excitations in the early 80s. Interestingly, the microtrabecular lattice idea WAS an artifact of early HVEM during this time.
Royal jelly is a honey bee secretion that is used in the nutrition of larvae, as well as adult queens. It is secreted from the glands in the hypopharynx of worker bees, and fed to all larvae in the colony, regardless of sex or caste.
"The honey bee queens and workers represent one of the most striking examples of environmentally controlled phenotypic polymorphism. In spite of their identical clonal nature at the DNA level, they are strongly differentiated across a wide range of characteristics including anatomical and physiological differences, longevity of the queen, and reproductive capacity. Queens constitute the sexual caste and have large active ovaries, whereas workers have only rudimentary, inactive ovaries and are functionally sterile. The queen/worker developmental divide is controlled epigenetically by differential feeding with royal jelly; this appears to be due specifically to the protein royalactin. A female larva destined to become a queen is fed large quantities of royal jelly; this triggers a cascade of molecular events resulting in development of a queen. It has been shown that this phenomenon is mediated by an epigenetic modification of DNA known as CpG methylation. Silencing the expression of an enzyme that methylates DNA in newly hatched larvae led to a royal jelly-like effect on the larval developmental trajectory; the majority of individuals with reduced DNA methylation levels emerged as queens with fully developed ovaries. This finding suggests thatDNA methylation in honey bees allows the expression of epigenetic information to be differentially altered by nutritional input."
Studies in germ-free (GF) mice demonstrate that the gut microbiota (GM) is a regulator of bone mass.The GM affects bone mass via effects on the immune status, which in turn regulates osteoclastogenesis.Probiotic and prebiotic treatments may impact GM composition and affect bone metabolism.The GM may be a novel therapeutic target for osteoporosis.
The gut microbiota (GM), the commensal bacteria living in our intestine, performs numerous useful functions, including modulating host metabolism and immune status. Recent studies demonstrate that the GM is also a regulator of bone mass and it is proposed that the effect of the GM on bone mass is mediated via effects on the immune system, which in turn regulates osteoclastogenesis. Under normal conditions, the skeleton is constantly remodeled by bone-forming osteoblasts (OBs) and bone-resorbing osteoclasts (OCLs), and imbalances in this process may lead to osteoporosis. Here we review current knowledge on the possible role for the GM in the regulation of bone metabolism and propose that the GM might be a novel therapeutic target for osteoporosis and fracture prevention.
The team then looked at the other 12 lineages and found exactly the same pattern. The origin of every major archaeal group was marked by the acquisition of bacterial genes—sometimes dozens, sometimes thousands. They borrowed, then they branched out. “The implication here is that such transfers played an important role in the actual establishment of the groups themselves,” says John Archibald from Dalhousie University.
“It was a surprise for us,” says Bill Martin from Heinrich-Heine University in Dusseldorf, who led the study. “You might ask why no one else has seen this before.” It’s probably because most scientists focused on the essential “core genes” that are common to all archaea. But the core genes comprise just 1 percent of the genome. They can tell us the shape of the archaeal family tree, but they say nothing about the characteristics that define the branches. To do that, you need to look at the entire genome, which is exactly what Nelson-Sathi did.
The “horizontal gene transfers” that he found are alien to us humans, who can only pass genes from parent to child. But bacteria and archaea don’t suffer the yoke of vertical inheritance. They can pass genes to one another with great ease.
These transfers could flow in either direction but in reality, they were mostly one-way. Nelson-Sathi found that bacteria have donated gene families to archaea five times more frequently than vice versa, and none of the archaea-to-bacteria transfers correspond to the rise of major bacterial groups. Bacteria have repeatedly thrust their archaeal peers into new evolutionary directions, but the reverse isn’t true.
"A talk given at Schumacher College (UK), Dartington on May 7th 2014.
The great challenge of our time is to build and nurture sustainable communities, designed in such a manner that their ways of life, physical structures, and technologies do not interfere with nature's inherent ability to sustain life. To do so, requires a new ecological understanding of life, as well as a new kind of "systemic" thinking.
In this lecture, Fritjof Capra describes that such a new understanding of life in terms of complexity, networks, and patterns of organization, has recently emerged at the forefront of science. He will emphasize, in particular, the new conception of the nature of mind and consciousness, which is one of the most radical philosophical implications of the systemic understanding of life; and the urgency of this new understanding for dealing with our global ecological crisis and protecting the continuation and flourishing of life on Earth.
Fritjof Capra was speaking as part of his short course running at Schumacher College."
Colbert Sesanker's insight:
In the book he describes systemic thinking as if it is non-mechanistic and somehow makes room for qualia, social and political issues. There is nothing presented to suggest living organisms are more than 'machines'. Also implicitly assumes that systemic thinking is what allowed us to break off cartesian dualism and into panpsychism.
We develop a general formalism for representing and understanding structure in complex systems. In our view, structure is the totality of relationships among a system's components, and these relationships can be quantified using information theory. In the interest of flexibility we allow information to be quantified using any function, including Shannon entropy and Kolmogorov complexity, that satisfies certain fundamental axioms. Using these axioms, we formalize the notion of a dependency among components, and show how a system's structure is revealed in the amount of information assigned to each dependency. We explore quantitative indices that summarize system structure, providing a new formal basis for the complexity profile and introducing a new index, the "marginal utility of information". Using simple examples, we show how these indices capture intuitive ideas about structure in a quantitative way. Our formalism also sheds light on a longstanding mystery: that the mutual information of three or more variables can be negative. We discuss applications to complex networks, gene regulation, the kinetic theory of fluids and multiscale cybernetic thermodynamics.
An Information-Theoretic Formalism for Multiscale Structure in Complex Systems Benjamin Allen, Blake C. Stacey, Yaneer Bar-Yam
"Few people remember Turing's work on pattern formation in biology (morphogenesis), but Turing's famous 1936 paper On Computable Numbers exerted an immense influence on the birth of molecular biology indirectly, through the work of John von Neumann on self-reproducing automata, which influenced Sydney Brenner who in turn influenced Francis Crick, the Crick of Watson and Crick, the discoverers of the molecular structure of DNA. Furthermore, von Neumann's application of Turing's ideas to biology is beautifully supported by recent work on evo-devo (evolutionary developmental biology). The crucial idea: DNA is multi-billion year old software, but we could not recognize it as such before Turing's 1936 paper, which according to von Neumann creates the idea of computer hardware and software."
Colbert Sesanker's insight:
The most interesting part is the relationship between innovation and incompleteness. There is too much deification of the static DNA sequence. Regardless, the only thing this abstraction requires is that the heritable information can be represented by a binary sequence.
"Masao Ito is Special Advisor to the RIKEN Brain Science Institute, Japan. He received the Fujiwara Prize (1981), the Academy Prize and Imperial Prize (1986), the Robert Dow Neuroscience Award (1993), the IPSEN Foundation Award (1993), the Person of Cultural Merit (1994), the Japan Prize (1996), Order of Culture (1996), and an Honorary Degree of Science from The University of Southern California (1995) and from Torino University (1996). Dr. Ito's field is neuroscience. He discovered the inhibitory action of cerebellar Purkinje cells, and the characteristic synaptic plasticity, long-term depression (LTD), in these cells. Based upon these findings, he developed a theory that the cerebellum is a general learning machine for acquiring not only motor skills, but also implicit memory in thought."
"To get at the details of the subtle effects of deliberate practice, Hesheng Liu1 and I recently proposed a thoroughgoing neurophysiological explanation of the child prodigy (Vandervert & Liu, in press). Our explanation is based upon the collaboration of working memory and cognitive functions of the cerebellum (Ito, 1997, 2005; Vandervert, 2003a, b; Vandervert et al., 2007). In our approach all repetitive working memory processes taking place in the cerebral cortex (e.g., in deliberate practice) are adaptively modeled in the cerebellum (see Ito, 1997, 2005; Chein et al., 2003; Vandervert et al., 2007). When the resulting cerebellar control models are fed back to working memory areas of the cortex, the thought processes of working memory become faster, higher in attentional control, and more appropriately and optimally timed (Akshoomoff et al., 1997; Ito, 1997, 2005; Ivry, 1997).
The above newer role of the ‘cognitive cerebellum’ (see Schmahmann, 1997; Ramnani, 2006) offers needed detailed support for Ericsson et al.’s proposal. In addition to the cerebellum constructing adaptive models of mental activity occurring in working memory, it has been convincingly argued that the cerebellum does this in the form of multi-pairs of models that constitute complex modular architectures for mental processes that when fed to working memory functions in the cerebral cortex act to facilitate the development of new, higher levels of performance (Haruno et al., 1999; Wolpert et al., 2003)."
The collected data reveals a startling picture. While each of the prodigies demonstrated an at least moderately elevated level of intelligence, the prodigies' full scale IQ scores were not consistently on the extreme end of the spectrum. What was consistently extraordinary, however, was the child prodigies' working memory scores—a category in which every prodigy tested in the 99th percentile. Additional results suggest a previously unknown connection between child prodigies and autism. The prodigies' family histories yielded an unlikely number of autistic relatives. And the child prodigies received elevated AQ scores with respect to attention to detail, a trait associated with autism. The prodigies did not, however, display many of the other traits typically associated with autism.
Colbert Sesanker's insight:
"What was consistently extraordinary, however, was the child prodigies' working memory scores—a category in which every prodigy tested in the 99th percentile. " Supports Vandervert's proposal?
int"At the same time, chaos has its advantages. On a behavioral level, the arms race between predator and prey has wired erratic strategies into our nervous system.1 A moth sensing an echolocating bat, for example, immediately directs itself away from the ultrasound source. The neurons controlling its flight fire in an increasingly erratic manner as the bat draws closer, until the moth, darting in fits, appears to be nothing but a tumble of wings and legs. More generally, chaos could grant our brains a great deal of computational power, by exploring many possibilities at great speed."
What are the neural signatures of consciousness? This is an elusive yet fascinating challenge to current cognitive neuroscience, but it takes on an immediate clinical and societal significance in patients diagnosed as vegetative and minimally conscious. In these patients, it leads us to ask whether we can test for the presence of these signatures in the absence of any external signs of awareness. Recent conceptual advances suggest that consciousness requires a dynamic balance between integrated and differentiated networks of information exchange between brain regions. Here we apply this insight to study such networks in patients and compare them to healthy adults. Using the science of graph theory, we show that the rich and diversely connected networks that support awareness are characteristically impaired in patients, lacking the ability to efficiently integrate information across disparate regions via well-connected hubs. We find that the quality of patients' networks also correlates well with their degree of behavioural responsiveness, and some vegetative patients who show signs of hidden awareness have remarkably well-preserved networks similar to healthy adults.