My articles

The HOX code - a nightmare for proponents of Evolution

In order to know what mechanisms eventually provoke change and if unguided evolution of an organism is a viable explanation, it must be known what mechanisms do form phenotype,  body architecture, organs, various cell types, cell migration etc. Development biology ( Evo-devo ) is a rather new branch of biology, but, yesterday, I gave a look at the book   Development biology, Gilbert / Barresi. 11th ed 2018. Despite studying biology for years, I had the impression to know almost nothing of what is described there. Development biology might be the most complex branch of biology, and many open questions remain.

Homeoboxes have been found in fungi, plants and animals. In each "kingdom" homeobox genes occupy a key position in the genetic control of either cell differentiation, morphogenesis and or body plan specification.

All Hox genes and many other developmental transcription factors contain the homeobox,  known for their colinearity: conserved arrangement on chromosomes that is the same as their order of activation along the body axis. The regulation is very precise.  The degree of sequence conservation of the homeodomain is extremely high indicating strong functional constraints leading to a high pressure to retain the homeobox sequences constant.

What the Hox code represents is a somewhat digital mechanism for regulating axial patterning. By mixing and matching combinations of the expression of a small number of Hox genes, organisms generate a greater range of morphological possibilities.

It is obvious that not any arrangement of Homeobox genes will give rise to functional body architecture. The precise arrangement is key to have functional body plans.  Mutations in hox genes do produce aberrant body plans..like legs where there should be antennae in fruit flies. But it is a mistake to assume that this is evidence that hox genes causally lay out the body plan, just like it would be a mistake to assume that a fault in a TV, causing a disruption in the reception of the signal, shows that the TV box produces the signal itself. Linear DNA cannot produce 3D form. There is a higher orchestration, which directs the correct linear arrangement of Homeobox genes in the genome.

Hox Genes in Development: The Hox Code
https://www.nature.com/scitable/topicpage/hox-genes-in-development-the-hox-code-41402

This colinearity, arrangement, order of activation and precise regulation of Hox gene clusters indicates there is a HOX Code, which sets the right pattern of Hox gene cluster arrangement for correct sequential expression of segments and rhombomeres in the embryo.  

There is uncertainty in our understanding of homeobox gene cluster evolution at present. This relates to our still rudimentary understanding of the dynamics of genome rearrangements and evolution over the evolutionary timescales being considered when we compare lineages from across the animal kingdom.

The mechanisms responsible for the synchronous regulation of Hox genes and the molecular function of their colinearity remain unknown. Despite 35 years of active research, the mechanisms of Hox gene regulation have remained elusive. It has been argued that chromatin structure and histone demethylation play important roles in activation of Hox genes, but the mechanism precisely directing chromatin modifications to specific loci at the right time remains mysterious.

What does this elucidate? Life is not only composed of organic carbon-based matter but essentially, instructional information. Not any kind of information, but complex, specifying information, blueprints, which precisely orchestrates and directs how to develop, build, adopt animals, plants, fungi, bacterias, and perpetuate life in all its various forms.

1. Cells store codified information in DNA, and at least 18 epigenetic codes, which are complex instructional informational blueprints, essential for cells to make copies of themselves, animal development, adaptation, and body architecture
2. All Codes, and blueprints we know the origin of come from an intelligent mind. Evolution is a non-directed, non-intelligent process and does not suffice to explain the origin of biodiversity and body architecture.
3. Therefore we have 100% inference that DNA comes from an intelligent mind and 0% inference that it is not.


The Hox Code, Code biology, Barbieri, page 107
In 1979, David Elder proposed a model that was capable of accounting for the regularities that exist in the bodies of many segmented worms (annelids). The segments of these animals are often subdivided into annuli whose number varies according to a simple rule: if a segment contains n annuli, the following segment contains either the same number n (repetition) or n plus or minus 1 (digital modification). Elder noticed that this type of rules is known to the designers of electronic circuits as a Gray code, a code that is binary (because it employs circuits that have only one of two states), combinatorial (because its outcomes are obtained by combinations of circuits) and progressive (because consecutive outcomes must be coded by combinations that differ in the state of one circuit only). The results obtained with these rules describe with great accuracy what is observed in segmented worms, and Elder proposed therefore that the body plan of these animals is based on a combinatorial code that is a biological equivalent of the Gray code. He underlined in particular that the coding principle cannot be the classical “one geneone pattern”, but “one combination of genes-one pattern” and for this reason he called it epigenetic code (Elder 1979). After the discovery of the Hox genes, it became increasingly clear that they are used in many different permutations, according to a combinatorial set of rules that became known as Hox code. The term Hox code was introduced independently by Paul Hunt and colleagues (1991) and by Kessel and Gruss (1991) to account for the finding that the individual characteristics of the vertebrae are determined by different combinations of Hox genes. Later on, it was found that this is true in most other organs and it became standard practice to refer to any combination of Hox genes as a Hox code. The epigenetic code proposed by Elder, in particular, is a Hox code because it is Hox genes that are responsible for the body plan of the segmented worms. It must be underlined that the Hox genes can be used in different combinations not only in various parts of a body, but also in different stages of embryonic development. At the phylotypic stage, for example, the Hox genes specify characteristics of the phylum, whereas in later stages they determine characteristics at lower levels of organization. There is, in short, a hierarchy of Hox gene expressions, and therefore a hierarchy of Hox codes. At this point, however, we have to face a key definition problem: is it legitimate to say that the Hox codes are true organic codes? More precisely, that they have the basic features that we find, for example, in the genetic code? An organic code is a mapping between two independent worlds and cannot exist without a set of adaptors that physically realize the mapping. The Hox codes have been defined instead as patterns of combinatorial gene expression and do not require adaptors because a molecular pattern in one world is not a mapping between two independent worlds. We have therefore two different definitions of code, one based on mapping and the other on patterns, or sequences, and it is important to keep them separate because they have different biological implications.

The various codes in the cell
https://reasonandscience.catsboard.com/t2213-the-various-codes-in-the-cell

The Genetic Code
The Splicing Codes
The Metabolic Code
The Signal Transduction Codes
The Signal Integration Codes
The Histone Code
The Tubulin Code
The Sugar Code
The Glycomic Code
The non-ribosomal code
The Calcium Code
The RNA code
A domain substrate specificity code of Nonribosomal peptide synthetases (NRPS)
The DNA methylation Code
The coactivator/corepressor/epigenetic code
The transcription factor code
The post-translational modification code for transcription factors
The HOX Code

Charles Darwin attended a Church of England school. With the aim of becoming a clergyman, he went to the University of Cambridge and studied Anglican theology.

As a non-conformist, he, like many apostates, and founders of sects, invented a branch of the religion called natural atheology

Natural Atheology
https://www.cambridge.org/core/books/darwinian-heresies/natural-atheology/61E8212A6EAC59F908A6D83F6ADA7B82

becoming its Pope, high-priest, bishop, and main evangelist and propagandist. A true all-in-one job. He is the author of the naturalists Bible, the famous book On the Origin of Species by means of natural selection, published on 24 November 1859.

Today, after almost 160 years, his religion is wide-spread, in special amongst evolutionary biologists and biochemists, atheists and agnostics, and widely taught in public schools, and has still resisted the growing evidence provided by scientific inquiry and advance, demonstrating that the real mechanisms that guide speciation, evolution, grow, phenotype formation, body architecture, development and biodiversity at large depend on guided pre-programming, various genetic and epigenetic codes and languages, sophisticated information selection, encoding, transmission, decoding, and interdependent biological principles - specialization, messaging, stigmergy and apoptosis.

As such, his hypothesis of mindless mutations and natural selection, and later, genetic drift and gene flow have been shown to be demonstrably false, and his postulates remain in the realm of blind faith, and his followers follow his footsteps as Popes, pastors, evangelists, propagandists influencing many, infesting the minds of the incautious and uneducated, which firmly believe that natural causes have the capacity to replace intelligence of the highest order to implement the most complex Uber computers, and veritable High-tech factory complexes, more complex than any factory made by man: biological Cells.

Hosea 4.6: My people are destroyed from lack of knowledge.

Despite the common attacks from the atheist camp, we need to learn, to be more gracious, that we respond their insults by either remain quiet, or leave the debate when it fits, without lower the level, and show them that we adopt a spirit of love ( and as such, be morally superior to them ). But we need to demonstrate also strength and courage, being bold and fearless, secure and convinced of what we believe, and that we adopt reason and logic in our thinking. And that strength comes from showing them that we can both: believe in the supernatural, and miracles, but at the same time well understand the natural world and its inner workings, as far as science permits. And show, that the natural world points, yeah, breaths, even screams out in all its levels and dimensions, from the extreme precision and fine-tuning of the atoms and its forces to the formidable engineering in the molecular world and the sophisticated language employed in DNA, to the colorful beauty of nature, to the whole universe and its extreme tuning: design !!

They might not understand the language of the natural world, and what it transmits to us because their mind is darkened by their will to deny God. But God does, when he wills so and draws the unbeliever to him, and when the atheist's eyes are open, he suddenly sees differently. His blinkers fall off. Our worldview grows and takes form by putting the pieces of information together, bit by bit. One information here, another there. When an atheist finally permits the truth to reach him, his intellectual cognitive dissonance is removed, and an aha moment is the starting point to get things straight. That's when intellectual satisfaction comes to his mind and his heart. That's when his soul begins to breathe, and God begins to shine in his heart, and the warmth of his love to give him peace.

John 1:3 Through him ( Christ) all things were made; without him nothing was made that has been made.

Psalm 19:1-4“ The heavens declare the glory of God; the skies proclaim the work of his hands. Day after day they pour forth speech; night after night they display knowledge. There is no speech or language where their voice is not heard. Their voice goes out into all the earth, their words to the ends of the world.”

Nehemiah 9:6 "You alone are the LORD You have made the heavens, The heaven of heavens with all their host, The earth and all that is on it, The seas and all that is in them You give life to all of them And the heavenly host bows down before You.

Isaiah 66:2 "For My hand made all these things, Thus all these things came into being," declares the LORD "But to this one I will look, To him who is humble and contrite of spirit, and who trembles at My word.

Origins - what cause explains best our existence, and why? Philosophy and theology

The first  three chapters are :

Chapter 1: Science only? Is science the only way to find truth?
Chapter 2: The God hypothesis
Chapter 3: The Theory of Intelligent Design

This is the link for download. The format is PDF:
https://ln.sync.com/dl/aecf30f00/7g99fwx5-6kt8y2mx-7427w6dd-nxwd5ep9

you will find the same information as well at my library::
https://reasonandscience.catsboard.com/t2742-origins-what-cause-explains-best-our-existence-and-why-philosophy-and-theology

Origins - what cause explains best our existence, and why? 

Molecular biochemistry, biology, the origin of life and biodiversity, systematically analyzed from a universal perspective
https://reasonandscience.catsboard.com/t2590-origins-what-cause-explains-best-our-existence-and-why

Thermodynamics and science predictions

It is often praised, how science based on methodological naturalism serves to make accurate predictions. Let's imagine that we would be aliens, being part of a super-intelligent civilisation. visiting early earth four billion years ago with a spaceship. We would find a hostile environment, no life, just spewing volcanoes etc.

We would leave, returning to our own planet, run a computer simulation, and make a prediction of how the earth would look like, 4 billion years later, and trying to simulate the effects that the four known forces of physics would have on every atom and every subatomic particle on our planet.

If we ran such a simulation out to the present day, would it predict that the basic forces of Nature would reorganize the basic particles of Nature into libraries full of encyclopedias, science texts and novels, nuclear power plants, aircraft carriers with supersonic jets parked on deck, and computers connected to laser printers, CRTs and keyboards?

If we graphically displayed the positions of the atoms at the end of the simulation, would we find that cars and trucks had formed, or that supercomputers had arisen? Certainly, we would not, and adding sunlight to the model would not help much.

The argument of thermodynamics was popular and often used by creationists, over a decade ago, but has gone a little bit abandoned in more recent Facebook times. The standard answers by atheists were that the earth is not closed, but an open thermodynamic system, receiving constantly energy through sunlight, which could decrease rather than increase entropy, so the argument is moot.

The Earth is an open system, it receives energy from the sun and entropy can decrease in an open system, as long as it is ‘‘compensated’’ somehow by a comparable or greater increase outside the system.

Isaac Asimov replied through an article at the Smithsonian journal:
You can argue, of course, that the phenomenon of life may be an exception [to the second law]. Life on earth has steadily grown more complex, more versatile, more elaborate, more orderly, over the billions of years of the planet’s existence. From no life at all, living molecules were developed, then living cells, then living conglomerates of cells, worms, vertebrates, mammals, finally Man. And in Man is a three-pound brain which, as far as we know, is the most complex and orderly arrangement of matter in the universe. How could the human brain develop out of the primeval slime? How could that vast increase in order (and therefore that vast decrease in entropy) have taken place?

Asimov concludes that the second law is not really violated, because: Remove the sun, and the human brain would not have developed . . . . And in the billions of years that it took for the
human brain to develop, the increase in entropy that took place in the sun was far greater; far, far greater than the decrease that is represented by the evolution required to develop the human brain.

Similarly, Peter Urone, in College Physics, wrote:
Some people misuse the second law of thermodynamics, stated in terms of entropy, to say that the existence and
evolution of life violate the law and thus require divine intervention. . . . It is true that the evolution of life from inert
matter to its present forms represents a large decrease in entropy for living systems. But it is always possible for the
entropy of one part of the universe to decrease, provided the total change in entropy of the universe increases.

The Theism VS Atheism debate is ALL about probability.

The reason natural forces can turn a computer or a spaceship into rubble and not vice versa is probability: of all the possible
arrangements atoms could take, only a very small percentage could add, subtract, multiply and divide real numbers, or fly
astronauts to the moon and back safely.

If an increase in order is extremely improbable when a system is closed, it is still extremely improbable when the system is
open, unless something is entering which makes it not extremely improbable.

The claim that the second law does not apply to open systems was invented in an attempt to avoid the evident implications and logical inference of a creator.

The missing ingredient is information.

Norbert Weiner - MIT Mathematician - Father of Cybernetics

"Information is information, not matter or energy. No materialism which does not admit this can survive at the present day."

Life is permeated by codified information. Not only genetic but mostly, epigenetic information. Complex blueprints, which direct how the most complex high-tech factory complex of the universe, biological cells, have to be built, and how to error check and repair themselves all along the production process of higher molecular machines, how to generate energy in the form of ATP molecules, how to import the basic, life-essential elements, purify them, use them to  build the basic building blocks of life like RNA, DNA, amino acids, carbohydrates and fatty acids, how to create a homeostatic ambiance permitting information exchange and signaling networks to operate, how to react to ecological cues, how to develop, and how to respond to nutritional demands. And it had all to be pre-programmed and set up in advance for life to kick off - without evolution.

This coincides with the REMARKABLE, awe -, well, actually the God-inspired beginning of the Gospel of John:

1 In the beginning was the Word, and the Word was with God, and the Word was God. 2 He was with God in the beginning. 3 Through him all things were made; without him nothing was made that has been made.

Science and religion are not at war, but actually complementary. One informs the other, and vice-versa. They are the same coin, one side showing the face, and the other side the numbers. Both point to God. A God that does not hide himself, but made himself known to us. John continues in verse 14:

The Word became flesh and made his dwelling among us. We have seen his glory, the glory of the one and only Son, who came from the Father, full of grace and truth.

What a remarkable revelation !! Praise the Lord.

What is remarkable as well about the above text is that it was essentially formatted as a scientific paper.

The article, ‘‘A Second Look at the Second Law,’’ by Dr. Granville Sewell, Professor of Mathematics at University of Texas at El Paso, was submitted on October 21, 2010 to the Journal of Applied Mathematics Letters. Dr. Sewell’s article was peer-reviewed and accepted for publication on January 19, 2011.

On March 2, 2011, the Editor-in-Chief of Applied Mathematics Letters, Dr. Ervin Rodin, decided to withdraw the article without consultation with the author, not because of any errors or technical problems found by the reviewers or editors, but because the Editor-in-Chief subsequently concluded that the content was more philosophical than mathematical and, as such, not appropriate for a technical mathematics journal such as Applied Mathematics Letters.

Truth is, the REAL problem was that it was Intelligent Design-friendly. Then , afterwards:

Applied Mathematics Letters, which agreed to apologize to Intelligent Design-friendly Texas professor Granville Sewell and have its publisher, Elsevier, pay $10,000 in legal fees, has posted the text of its apology

http://retractionwatch.com/2011/06/13/applied-mathematics-letters-posts-apology-for-retracting-intelligent-design-friendly-paper/

The Journal of Applied Mathematics Letters and its Editor-in-Chief, Dr. Rodin, provide their sincere and heartfelt apologies to Dr. Sewell for any inconvenience or embarrassment that may have been caused by their unilateral withdrawal of his article, and wish Dr. Sewell the best in the future and welcome Dr. Sewell’s submission of future articles for possible publication.

Dr. Sewell’s article as accepted by Applied Mathematics Letters can be viewed at:
http://www.math.utep.edu/Faculty/sewell/AML_3497.pdf


Take proteins.
The natural tendency of proteins is to fall apart; for proteins to be synthesized, the reaction must be driven up the thermodynamic hill, away from equilibrium. The same is true of other biochemical processes: the transport of nutrients against a concentration gradient, the generation of physical force or electrical potentials, even the accurate transmittal of genetic information, all represent work in the thermodynamic sense. They can take place only because cells couple the work function to a source of energy. This, in fact, is how energy is defined: it is the capacity to do work. Bioenergetics revolves around the sources of biological energy, and the mechanisms by which energy is coupled to useful work

" There is no evidence of God ". Really?
That's one of the arguments most frequently brought forward by unbelievers. What they, however, want to say is: There is no evidence that points ( in his view ) to God. The problem is the lens and a priori assumption someone adopts, and what someone wishes to be true. The evidence is for all of us the same. The observable world. The tool to make rational conclusions, too: Our mind. The conclusion we make on how everything came to be, depends on the interpretation of the evidence and reality. While some are gullible towards the claim that natural mechanisms created everything, the theist is incredulous towards that view.

The theist is incredulous towards the claim that :
Ignorance about origins is justified. The universe exists without beginning or was made from nothing.  Randomness produced cosmological and biochemical fine-tuning. Chaos produced order. Non-life produced life.  Matter produced codes, and instructional blueprints, signalling, and information transmission networks. Computers, computer networks, molecular machines, assembly lines, and high-tech factory parks, consciousness, and objective moral values.  

  

Exotic life sites: The feasibility of far-out habitats

1. If Abiogenesis were true, and life could emerge naturally and the building blocks could self-assemble spontaneously by orderly aggregation and sequentially correct manner without external direction, and finely tuned planets to host life as well, then the universe with 1 billion trillion stars, and 10 billion galaxies, each with about 100 billion stars, should host many planets hosting the right conditions, and life. A new tally proposes that roughly 700 quintillion terrestrial exoplanets are likely to exist across the observable universe—most vastly different from Earth. …that means that either we are the result of a very improbable lottery draw or we don’t understand how the lottery works.” None of the known 700 quintillion possible planets looks like Earth.

2. Paul Davies:  This number, gigantic as it may appear to us, is nevertheless trivially small compared with the gigantic odds against the random assembly of even a single protein molecule. Though the universe is big, if life formed solely by random agitation in a molecular junkyard, there is scant chance it has happened twice. As just a starting point, consider that many statisticians consider that any occurrence with a chance of happening that is less than one chance out of 10^50, is an occurrence with such a slim a probability that is, in general, statistically considered to be zero. The data demonstrate that the probability of finding even one planet with the capacity to support life falls short of one chance in 10^140 (that number is 1 followed by 140 zeros).

3. Our life is not a cosmic accident but planned and implemented by a powerful intelligent Creator.

EXOTIC LIFE SITES: THE FEASIBILITY OF FAR-OUT HABITATS
https://reasonandscience.catsboard.com/t232-life-on-other-planets-a-real-possibility

Abiogenesis is impossible
https://reasonandscience.catsboard.com/t1279-abiogenesis-is-impossible

Calculations of life beginning through unguided, natural, random events.
https://reasonandscience.catsboard.com/t2508-calculations-of-life-beginning-through-unguided-natural-random-events

FineTuning of the earth
https://reasonandscience.catsboard.com/t1415-finetuning-of-the-earth

Paley's watchmaker argument: Debunked?

I hear it often: Paley's watchmaker argument has been debunked many times. I think the opposite is the case. It has been consolidated, more and more.

Paley's watchmaker argument

https://reasonandscience.catsboard.com/t2608-paley-s-watchmaker-argument

William Paley (July 1743 – 25 May 1805) was an English clergyman, Christian apologist, philosopher, and utilitarian. He is best known for his natural theology exposition of the teleological argument for the existence of God in his work Natural Theology or Evidences of the Existence and Attributes of the Deity, which made use of the watchmaker analogy. 1

I love analogies, and Paley's watchmaker analogy is a classic:

In WILLIAM PALEY's  book  :
Natural Theology or Evidence of the Existence and Attributes of the Deity, collected from the appearances of nature  2, page 46, he writes :

In crossing a heath, suppose I pitched my foot against a stone, and were asked how the stone came to be there, I might possibly answer, that, for anything I knew to the contrary, it had lain there for ever: nor would it perhaps be very easy to shew the absurdity of this answer. But suppose I had found a watch* upon the ground, and it should be inquired how the watch happened to be in that place, I should hardly think of the answer which I had before given, that, for anything I knew, the watch might have always been there. Yet why should not this answer serve for the watch, as well as for the stone? Why is it not as admissible in the second case, as in the first? For this reason, and for no other, viz. that, when we come to inspect the watch, we perceive (what we could not discover in the stone) that its several parts are framed and put together for a purpose, e.g. that they are so formed and adjusted as to produce motion, and that motion so regulated as to point out the hour of the day; that, if the several parts had been differently shaped from what they are, of a different size from what they are, or placed after any other manner, or in any other order, than that in which they are placed, either no motion at all would have been carried on in the machine, or none which would have answered the use, that is now served by it.

My comment: Without knowing about biology as we do today, Paley made an observation, which is spot on, and has astounding significance and correctness, applied to the reality of the molecular world. Let's list the points he mentioned again:

- parts differently shaped
- different size
- placed after any other manner
- or in any other order

no motion would be the result.

That applies precisely as well to biological systems, and cells. Each of these four points must evolve correctly, or no improved or new biological function is granted. How many mutations would be required to get from a unicellular organism to multicellular organism? Would evolution not have to go in a gradual slow, increasing manner from one eukaryotic cell to an organism with two cells,   3 cells, and so on,  to get in the end an organism with millions, and billions of cells?  Let's suppose there were unicellular organisms, and evolutionary pressure to go from one to two cells. What and how many mutations would be required in the genome?

The interdependent and irreducible structures required to make proteins

https://reasonandscience.catsboard.com/t2039-the-interdependent-and-irreducible-structures-required-to-make-proteins

To make proteins, and direct and insert them to the right place where they are needed, at least 25 unimaginably complex biosyntheses and production-line like manufacturing steps are required. Each step requires extremely complex molecular machines composed of numerous subunits and co-factors, which require the very own processing procedure described below, which makes its origin an irreducible  catch22 problem.

Paul Davies, the origin of life, page 59
Proteins are a godsend to DNA because they can be used both as building material, to make things like cell walls, and as enzymes, to supervise and accelerate chemical reactions. Enzymes are chemical catalysts that ‘oil the wheels’ of the biological machine. Without them, metabolism would grind to a halt, and there would be no energy available for the business of life. Not surprisingly, therefore, a large part of the DNA databank is used for storing instructions on how to make proteins. Here is how those instructions get implemented. Remember that proteins are long-chain molecules made from lots of amino acids strung together to form polypeptides. Each different sequence of amino acids yields a different protein. The DNA has a wish list of all the proteins the organism needs. This information is stored by recording the particular amino acid sequence that specifies each and every protein on the list. It does so use DNA's four-letter alphabet A, G, C and T; the exact sequence of letters spells out the amino acid recipe, protein by protein – typically a few hundred base pairs for each. To turn this dry list of amino acids into assembled, functioning proteins, DNA enlists the help of a closely related molecule known as RNA (for ribonucleic acid). RNA is also made from four bases, A, G, C and U. Here U stands for uracil; it is similar to T and serves the same purpose alphabetically. RNA comes in several varieties; the one of interest to us here is known as messenger RNA, or mRNA for short. Its job is to read off the protein recipes from DNA and convey them to tiny factories in the cell where the proteins are made. These mini-factories are called ribosomes and are complicated machines built from RNA and proteins of various sorts. Ribosomes come with a slot into which the mRNA feeds, after the fashion of a punched tape of the sort used by old-fashioned computers.

Main topics on complex, specified/instructional coded information in biochemical systems and life

https://reasonandscience.catsboard.com/t2625-main-topics-on-complex-specified-instructional-coded-information-in-biochemical-systems-and-life

The problem of information

Norbert Weiner - MIT Mathematician - Father of Cybernetics
"Information is information, not matter or energy. No materialism which does not admit this can survive at the present day."

It has to be explained:

- a library index and fully automated information classification, storage and retrieval program ( chromosomes, and the gene regulatory network )
- The origin of the complex, codified, specified, instructional information stored in the genome and epigenetic codes to make the first living organism
- The origin of the Genetic Code
- How it got nearly optimal for allowing additional information within protein-coding sequences
- How it got more robust than 1 million alternative possible codes
- The origin of the over a dozen epigenetic codes
- The origin of the information transmission system, that is the origin of the genetic code itself, encoding, transmission, decoding and translation
- The origin of the genetic cypher/translation, from digital ( DNA / mRNA ) to analogue ( Protein )
- The origin of the hardware, that is DNA, RNA, amino acids, and carbohydrates for fuel generation
- The origin of the replication/duplication of the DNA
- The origin of the signal recognition particle
- The origin of the tubulin Code for correct direction to the final destination of proteins

Cell-intrinsic timing, biological clocks, cell division counting, and other mechanisms control the growth and division of cells.  Evolution, or design?  

This article is best read here:
https://reasonandscience.catsboard.com/t2739-cell-intrinsic-timing-biological-clocks-cell-division-counting-and-other-mechanisms-control-the-growth-and-division-of-cells-evolution-or-design

If each cell in our face were to undergo just one more cell division, we would be considered horribly malformed. If each cell in our arms underwent just one more round of cell division, we could tie our shoelaces without bending over. How do our cells know when to stop dividing? Our arms are generally the same size on both sides of the body. How is cell division so tightly regulated? 3

“A person's right and left legs almost always end up the same length, and the hearts of mice and elephants each fit the proper rib cage. How genes set limits on cell size and number continues to mystify.” 4 One of the remaining fundamental mysteries in biology is how organs and organisms were programmed to stop growing at the right time. This cessation or near cessation of growth does not occur abruptly, but rather is the end result of a progressive decline in growth rate.

It is difficult to examine conception, the division of cells, and the transition from zygote to the fetus and not see a rigorous and meticulous series of patterns begin to emerge. If random occurrence and simple chaotic incidence had been the cause for human life, one could expect a far greater number of genetic mutations, anomalies and aberrations. The symmetry of the human body from conception to birth is overwhelming, and it is extremely unlikely that random occurrence is responsible.

A variety of genes are involved in the control of cell growth and division. The cell cycle is the cell’s way of replicating itself in an organized, step-by-step fashion. This cycle of duplication and division, known as the cell cycle, is the essential mechanism by which all living things reproduce. The duplication of eukaryotic cells is an all fine-tuned biochemical processes that depend on the precise structural arrangement of the cellular components. The only way to make a new cell is to duplicate a cell that already exists. Tight regulation of this process ensures that a dividing cell’s DNA is copied properly, any errors in the DNA are repaired, and each daughter cell receives a full set of chromosomes. The cycle has checkpoints (also called restriction points), which allow certain genes to check for problems and halt the cycle for repairs if something goes wrong. A minimal number of Cell-cycle regulators are required, which makes them irreducibly complex. Why would a prebiotic soup, or, let's suppose, life began with simple cells which divide by fission, produce any of these regulators without the others, if by themselves, without the others, there is no function for them?

The Cell cycle
https://reasonandscience.catsboard.com/t2109-the-cell-cycle

If a cell has an error in its DNA that cannot be repaired, it may undergo programmed cell death (apoptosis). Apoptosis is a common process throughout life that helps the body get rid of cells it doesn’t need. Cells that undergo apoptosis break apart. Apoptosis is a tightly regulated process – controlled by the integration of multiple pro-and anti-apoptotic signals. Ultimately the induction of apoptosis occurs through the activation of the caspase proteases that are responsible for coordinating the hallmarks of an apoptotic death:  cell shrinkage, chromatin condensation, membrane blebbing and DNA fragmentation. Bad things happen when apoptotic pathways are disrupted. A shut down of the pathway through mutation allows for growth of cancer and neurological disorders

Apoptosis, or Programmed Cell Death, is key to multicellular life and multicellular computing. Orchestrated apoptosis helps the growing embryo to sculpt many aspects of its final form. It is also a part of normal "maintenance." Every year the average human loses perhaps half of his/her body weight in cells via apoptosis! Apoptosis also protects the organism from "rogue" cells because such cells self-destruct when their internal mechanisms go wrong unless the apoptosis mechanism itself is compromised, as happens in the development of cancer. 1 Because apoptosis is so crucial to the growth and survival of multicellular organisms, it is carefully intertwined with other three multicellular principles. In other words, computing will adopt eventually in the future architectures similar to multicellular
biological organisms.

The four biological principles - specialization, messaging, stigmergy and apoptosis - had to emerge together since they depend upon each other.  Interdependence is a hallmark of intelligent design. 2

Multicellular computing adopts these four major organizing principles of multicellular biological systems because they help tame the spiralling problems of complexity and out-of-control interactions in the Internet.
Human-made computer networks are far behind multicellular biological networks - a computer virus is able to affect millions of computers, an attack a few years ago is an example, where millions of computers were blocked, and the owners had to pay to get their operational system back. In life, when a cell drives havoc, it is isolated and self-destructs. The whole organism is not affected.  Multicellular computing is biomimetics at its best, and the WWW is moving forward to get close to what High-tech computer networks in cells and brain neuronal networks do. Apoptosis-like mechanisms will eventually be developed, to shut down or disconnect computers infected by viruses. Computer science can learn a lot from computing and signalling networks in multicellular organisms.

Each cell participates simultaneously in all four principles
Specialization - All healthy Metazoan cells are specialized. Even adult stem cells are somewhat specialized. What is perhaps the most specialized aspect of the cells, other than their unique shape and function, is their unique repertoire of message receptors that determine the set of message molecules to which they can respond. They all share common behaviours too. Included in the common behaviour are participation in the cues and signals of their stigmergy relationship with the rest of the body, and obedience to apoptosis messages. In other words, multicellular organisms are characterized by specialized behaviours,  appropriate messaging, stigmergy and apoptosis behaviours.

Polymorphic Messaging - Complex messenger proteins often act as "bundles" of messages. That is, one messenger protein may have separate domains, each with a different messaging function. And often, the different message domains address each of the other three architectural principles. For example, one domain initiates signal cascades specific to the unique specialized function of that type of cell, another domain on the same complex molecular messenger facilitates or verifies physical attachment to the extracellular matrix (i.e., deals explicitly with the stigmergy structure), and yet another provides signals that either suppress or encourage apoptosis! The existence of these multi-part messages shows how fundamental these principles are. A single multi-part message speaks to the functional relationship of the cell to the whole organism/tissue/organ rather than to just a single cell function.

Question: Does that indicate its origin in a stepwise, evolutionary fashion, or intelligent setup and implementation?

Stigmergy - Virtually all cells other than simple red blood cells that lack a nucleus and most organelles are affected by stigmergy cues and/or signals. Even unattached cells such as other blood and lymph born cells are affected by and affect blood borne stigmergy signals, e.g. hormones. Cells that are attached to the Extracellular Matrix (ECM), i.e., the stigmergy structure, leave long-lasting cues (persistent messages) in those structures that affect other cells. In turn, the cells respond to such cues in ways that may cause them to modify the physical structures; that's how the structures are built in the first place. Cells that are normally attached or in direct contact with the ECM require constant feedback from the ECM. Absent the appropriate attachment cues, they suicide (undergo apoptosis).

Apoptosis - Almost all cells except cancerous cells participate in apoptosis signalling all the time. Even very simple cells such as red blood cells that lack a nucleus can undergo apoptosis.

Body growth in animals is rapid in early life but then progressively slows, thus imposing a limit on adult body size. This growth deceleration in mammals is caused by potent suppression of cell proliferation in multiple tissues and is driven primarily by local, rather than systemic, mechanisms. 4  This progressive decline in proliferation results from a GENETIC PROGRAM that occurs in multiple organs and involves the down-regulation of a large set of growth-promoting genes. The limit on adult body size is imposed by a negative feedback loop. Different organs appear to use different types of information to precisely target their adult size. Organ size appears to be limited by the initial number of progenitor cells, suggesting a mechanism based on cell-cycle counting. Growth disorders result in the unrestrained growth of cancer. Growth of different organs and structures is coordinated temporally and conditionally to maintain proportionality of these body parts. Coordinated growth of different organs is that body growth is orchestrated by a hormonal or other systemic mechanisms. Biological clocks allow the body to grow for a defined period of time before slowing, thus achieving a certain size. Such timing mechanisms may be employed during embryonic development in certain cell types. Time, rather than the number of cell divisions, signals the start of differentiation, indicating the presence of a cell-intrinsic timing mechanism. Furthermore, other, even more complex regulatory mechanisms that consist of multiple components with overlapping functions guarantee that defects in one component do not totally abolish the timing function. In some developmental systems, growth appears to be limited by a cell-division counter. During the early development of Xenopus laevis, a counting mechanism is in place to ensure that the zygote divides exactly 12 times before cell division slows.

Genetic programming, regulation, set up negative feedback loops, precise targeting, cell-cycle counting, orchestration, biological clocks, cell-intrinsic timing mechanism, cell-division counting.  Design and programming by intelligence, or set up by unguided evolutionary development ? You decide. I certainly go with the first option.

1. https://bitesizebio.com/20969/apoptosis-gone-wrong-cell-deaths-role-in-disease/
2. http://evolutionofcomputing.org/Multicellular/IntertwinedPrinciples.html
3. Development biology, Gilbert / Barresi, page 3
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365796/

Is evolution a faith stopper?

1. Biodiversity is explained by evolution. Its a fact confirmed by science. And common ancestry is true.
2. This demonstrates that Genesis is false. No creator required. And abiogenesis, science is still working on it, but with time, will find all the answers.
3. God is not necessary. We have a worldview, that makes sense.

Dawkins 1986: "Although atheism might have been logically tenable before Darwin, Darwin made it possible to be an intellectually fulfilled atheist" (Dawkins 1986, 6)
Sometimes, when I point out, that evolution is defended with such vehemence to deny God, atheists not rarely object that and say: No. Even the pope believes in evolution.
Truth said I have seen many atheists use evolution as a pretext to deny Gods existence.

https://www.apologeticscentral.co.za/articles/ERV.html
The naturalist assumes that God doesn’t exist, and then constructs a theory that tries to explain natural occurrences as best he can without God. He then proceeds to claim he has proved God doesn’t need to exist. The problem is that the theory will show no need of God if that is the assumption that was started with.

Evolution or micro-evolution is actually best described as adaptation, and a life-essential process, and had to be setup when life began:

Adaptation of cells to new environments
https://reasonandscience.catsboard.com/t2061p125-my-articles#6174

Several life-essential EPIGENETIC mechanisms respond to environmental stress. 

- heat shock factors (HSFs)
- The unfolded protein response (UPR)
- nonhomologous end-joining and homologous recombination
- The DNA Damage Response
- The Response to Oxidative Stress

Evolution takes supposedly thousands of years to gain an environmental advantage. So what environmental benefit would evolution supposedly provide, if adapting and responding to environmental stimuli is not only a life-essential process which had to be fully implemented when life began but, furthermore, a pre-programmed process based on information through signaling networks?


Cells have many mechanisms to modulate the signaling pathways at transcriptional, post-transcriptional and post-translational levels. 

Organisms respond to short-term environmental changes by reversibly adjusting their physiology to maximize resource utilization while maintaining structural and genetic integrity by repairing and minimizing damage to cellular infrastructure, thereby balancing innovation with robustness. The cell’s initial response to a stressful stimulus is geared towards helping the cell to defend against and recover from the insult. 2 The fact that the cell’s survival critically depends on the ability to mount an appropriate response towards environmental or intracellular stress stimuli can explain why this reaction is highly conserved in evolution. The adaptive capacity of a cell ultimately determines its fate.

One of the reasons behind the evolutionary success of mammals (and other multicellular organisms) is their extraordinary capacity to adapt to changing environmental conditions. 3

Maybe the author should ask himself, how the Cell could have survived without the mechanism implemented from day one !!

Signalling and oscillations generated by membrane proteins on the surface of Cell membranes points to design

This article is best read here:
https://reasonandscience.catsboard.com/t2745-how-signaling-in-biology-points-to-design

Cell division is a key step in the life of a bacterium. This process is carefully controlled and regulated so that the cellular machinery is equally partitioned into two daughter cells of equal size. Most bacteria divide quite precisely and their daughter cells are often the same size. Rod-shaped bacteria that divide by binary fission, such as Escherichia coli, often mark their cell division sites at their cell midpoint so that daughter cells are roughly equivalent in size and shape. So how does E. coli know where its middle is?

Cell division is life-essential. It had to be fully implemented when life began. But mindless matter has no goals. Neither to become alive nor to perpetuate it. Cell division at the right place IMHO is life-essential. Bacterias have no knowledge. They had to be pre-programmed to divide in the middle. The "know-how" had to come from the implementer of the mechanism.  

One way to select the new mid-cell site would be to measure the distance from the two opposing cell poles, using a system that could recognize markers at those poles and define the spot furthest from both markers. This would require that both polar markers act negatively on cell division at equivalent intensities. The result would be a concentration gradient, with the lowest concentration of the negative regulator at the cell midpoint, the greatest distance from both cell poles. It turns out that E. coli and some other rod-shaped bacteria select their cell midpoint using such a negatively acting morphogen gradient, set up by the so-called  Min system.

In the bacterium Escherichia coli, the Min proteins oscillate between the cell poles to select the cell center as division site. This dynamic pattern has been proposed to arise by self-organization of these proteins, and several models have suggested a reaction-diffusion type mechanism, observed in a number of systems. Min proteins are crucial for accurate cell division and undergo spatiotemporal oscillations. They spontaneously organize into propagating wave patterns on supported membrane surfaces in the presence of ATP. The formation and maintenance of these patterns, which extend for hundreds of micrometres, require adenosine 5′-triphosphate (ATP), and they persist for hours.  Although the emergent behaviour is complex, the system can be quantitatively understood in terms of a reaction-diffusion model for membrane-surface inter­actions.  This system consists of the proteins MinC, MinD, and MinE which oscillate between the poles of the rod-shaped bacterium and thereby select the cell center as the site for division septum formation. The Min proteins are crucial for accurate cell division. Mutants lacking the Min system are prone to divide asymmetrically, which gives rise to DNA free minicells. ( from mini, the name Min proteins ). 

MinD recruits MinC to the membrane, and MinE induces MinC/MinD to oscillate rapidly between the membrane of opposite cell halves.  MinE stimulates the removal of MinD from the membrane in a wave-like fashion.  These waves run from a mid-cell position towards the poles in an alternating sequence such that the time-averaged concentration of division inhibitor is lowest at mid-cell.  Each component participates in generating a dynamic oscillation to ensure proper spatial and temporal regulation of chromosomal segregation and division.

Two separate, individual systems work as a team to perform the task. Is that not an irreducibly complex - / interdependent system, where one alone has no function? Had there not to be a planned endgoal beforehand, and complex problem-solving intelligence and mental input to program the function, to achieve the purpose of cell division, btw. essential for the perpetuation of life?


Centering the Z-Ring
One model of Z-ring formation permits its formation only after a certain spatial signal that tells the cell that it is big enough to divide. The high concentration of a FtsZ polymerization inhibitor at the poles prevents FtsZ from initiating division at anywhere but the mid-cell. By inhibiting FtsZ assembly at the cell poles, the Min system restricts the formation of the division septum to the cell-center.

How would and could non-directed, unguided, non-intelligent mechanisms arrive at such an elaborated mechanism, where an interplay of various different parts of the system are directed to a achieve a specific outcome, namely cell division, essential for the perpetuation of bacterial life on earth? It is an all or nothing business. Either all players are there, doing their assigned job, or cells do not divide. 

Biochemical oscillators

Cellular rhythms are generated by complex interactions among genes, proteins and metabolites. They are used to control every aspect of cell physiology, from signalling, motility and development to growth, division and death. 16 Biochemical oscillations occur in many contexts (such as metabolism, signalling and development) and control important aspects of cell physiology, such as circadian rhythms, DNA synthesis, mitosis and the development of somites in vertebrate embryos. In the 1950s and 1960s, the first clear examples of biochemical oscillations (in metabolic systems) were recognized in glycolysis.  Oscillators have systems-level characteristics (for example, periodicity, robustness and entrainment) that transcend the properties of individual molecules or reaction partners and that involve the full topology of the reaction network. 

The Min oscillator
Without MinD and MinE, MinC would simply inhibit cell division throughout the whole cell. MinD and MinE provide the localization cues that restrict MinC to zones near the cell poles and away from the cell midpoint, thus creating the desired bipolar concentration gradient of MinC. This gradient concentrates MinC near the cell poles and away from mid-cell, thus relieving the mid-cell site from its FtsZ disassembly activity. Remarkably, in E. coli this bipolar gradient of Min proteins is not static, but instead is characterized by wholesale migration of all three proteins from one cell pole to the other. MinC is not needed for this oscillation, but instead is a passenger on this endless ride, which cycles back and forth every 1 minute or so, depending on a number of factors, including temperature.


The oscillation is tuned to sense the geometry of a typical E. coli cell. If these rod-shaped cells become elongated, the Min proteins form multiple dynamic binding zones on the membrane that are regularly spaced, ∼7–10 μm apart. This spacing presumably represents the default distance that one MinD zone can stably form away from a MinE zone, which is longer than the 3–4 μm typical of an E. coli cell. In rod-shaped cells with branches, MinD will explore the different branches. Because only MinD and MinE are needed for the oscillation, the system mimics a nonlinear reaction-diffusion system.

Already in 1952, Alan Turing suggested a diffusion–reaction system as one mechanism to generate patterns of molecular concentrations. MinE is a topological factor which, together with MinD, provides the localization signals that restrict MinC to zones near the cell poles and away from the cell centre.  The consequence of this extraordinary protein oscillation is that the concentration of MinC is highest at the cell poles and lowest at the mid-cell where the Z-ring appears and, subsequently, the septum forms.


Bacterial Min system, due to evolution? 
The existence of two different Min systems is intriguing.  From the available data it is hard to infer which Min system evolved from which and it has been speculated that both Min systems evolved together in Gram-positive bacteria for alternate life cycles of vegetative growth and sporulation. 


Speculation. As always.As can be seen in the annexed picture, the wave oscillations are a beautiful orchestration, and the cell division process, requiring multiple players, indicates that it had to be set up all at once. A gradual evolutionary development would only result in failure, one after the other.

Evolution, or design ?

How Signaling in biology points to design

If I had to mention ONE word which refutes evolution by mutations and natural selection to explain biological development, body architecture, biodiversity, adaptation, regulation,  governing, controlling, recruiting, interpretation, recognition, orchestrating, elaborating strategies, guiding, it would be: SIGNALING.

Eukaryotic cells use signal-transduction networks to respond in specific ways to external signals from their environment. Several signal transduction pathways are composed of multi-step chemical reactions. Signal transduction is the process of routing information inside cells when receiving stimuli from their environment that modulate the behaviour and function. In such biological processes, the receptors, after receiving the corresponding signals, activate a number of biomolecules which eventually transduce the signal to the nucleus.  Signal transduction is a critical step in inter- and intra-cellular communication The specificity of cellular responses to receptor stimulation is encoded by the spatial and temporal dynamics of downstream signalling networks. Temporal dynamics are coupled to spatial gradients of signalling activities, which guide pivotal intracellular processes and tightly regulate signal propagation across a cell.

Cells respond to external cues using a limited number of signalling pathways that are activated by plasma membrane receptors, such as G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs). These pathways do not simply transmit, but they also process, encode and integrate internal and external signals.  It has become apparent that distinct spatiotemporal activation profiles of the same repertoire of signalling proteins result in different gene-expression patterns and diverse physiological responses. These observations indicate that pivotal cellular decisions, such as cytoskeletal reorganization, cell-cycle checkpoints and cell death (apoptosis), depend on the precise temporal control and relative spatial distribution of activated signal transducers.

RTK-mediated signalling pathways have been in the limelight of scientific interest owing to their central role in the regulation of embryogenesis, cell survival, motility, proliferation, differentiation, glucose metabolism and apoptosis. Malfunction of RTK signalling is a leading cause of important human diseases that range from developmental defects to cancer, chronic inflammatory syndromes and diabetes.

To understand the major trends in animal diversity and if the various kinds of morphology are due to evolution, we must first understand how animal form is generated. Above demonstrates that regulation of embryogenesis, cell survival, motility, proliferation, differentiation, glucose metabolism and apoptosis is due to  RTK-mediated signalling pathways, which play a central role in these processes, and as such, animal diversity and if the various kinds of morphology in the animal kingdoms.

Upon stimulation, RTKs undergo dimerization  (for example, the epidermal growth factor receptor (EGFR)) a or allosteric transitions (insulin receptor) that result in the activation of the intrinsic tyrosine kinase activity. Subsequent phosphorylation of multiple tyrosine residues on the receptor transmits a biochemical signal to numerous cytoplasmic proteins, thereby triggering their mobilization to the cell surface4,10. The resulting cellular responses occur through complex biochemical circuits of protein-protein interactions and covalent-modification cascades.

What is signalling?
Cells must be able to respond rapidly and precisely not only to changes in their external environment but also to developmental and differentiation cues to determine when to divide, die, or acquire a particular cell fate. Signal transduction pathways are responsible for the integration and interpretation of most of such signals into specific transcriptional states. 1 Those states are achieved by the modulation of chromatin structure that activates or represses transcription at particular loci.

Post-translational modifications (PTMs) of histones provide a fine-tuned mechanism for regulating chromatin structure and dynamics. PTMs can alter direct interactions between histones and DNA and serve as docking sites for protein effectors, or readers, of these PTMs. Binding of the readers recruits or stabilizes various components of the nuclear signalling machinery at specific genomic sites, mediating fundamental DNA-templated processes, including gene transcription and DNA recombination, replication and repair 2

The is crosstalk between signal transduction and its consequent changes in chromatin structure and, therefore, gene expression. There is a relationship between chromatin-associated proteins and important signal transduction pathways during critical processes like development, differentiation, and disease. There is a great diversity of epigenetic mechanisms that have unexpected interactions with signaling pathways to establish transcriptional programs.

Secular science is FULL of evidence of intelligent design and the requirement of intelligent setup, but suppresses this obvious fact,  by not pointing it out.  

Following, an example:

Signals to and within the cell are integrated at many levels to facilitate a meaningful outcome. 6
https://www.nature.com/articles/nsmb0610-641

In other words, meaningful means: purposeful, intelligible, suggestive.

How could natural, non-intelligent, non-conscient chemical reactions evolve into producing signalling molecules and proteins, carrying meaning, and signals, that inform receptors to perform a precise, specific action? - Not forgetting, that there has to be a common agreement of the signal transmitter, and the receptor, of what the signal means?

More goes on than just the linear, sequential flow of information. glycogen synthase kinase 3, for example, operates in multiple signal-transduction pathways. This network of pathways permits the cell to respond in a coordinated fashion to instructions sent from the environment. Cells use a network with hubs, where multiple factors are located, and these hubs are an ideal venue for coordinating a response.

A cell ’ s response to its environment is often determined by signalling through the actions of enzyme cascades. The ability to organize these enzymes into multiprotein complexes allows for a high degree of fidelity, efficiency and spatial precision in signalling responses. 7  Control of cell signalling events occurs at many levels. Classically, regulation of catalysis occurs via interactions with metabolites, cofactors or chemical messengers that allosterically modulate enzyme activity. Additionally, the post-translational modification of enzymes and effector proteins alters the binding properties and activity of these macromolecules. Together, these modifications act to adjust the flow of information through signal-transduction cascades.

So, on top of the signalling cascade, there is a second layer of information, which controls the signalling events, enzyme modification and effector proteins

Evolution, or design ?

The picture:
https://www.ndm.ox.ac.uk/principal-investigators/project/structure-and-dynamics-of-bacterial-chemotaxis-signalling-array-by-cryoem

Irreducible complexity has been debunked?

Let's see another awe-inspiring protein, which demonstrates, why the claim is false.
Multicellular organisms are characterized by

- specialized behaviours,
- appropriate messaging,
- stigmergy and
- apoptosis behaviours

Each eukaryotic cell participates simultaneously in all four principles.
Apoptosis, or Programmed Cell Death, is key to multicellular life and multicellular computing. Orchestrated apoptosis helps the growing embryo to sculpt many aspects of its final form. It is also a part of normal "maintenance."

The Akt-PI3K pathway is essential for cell survival as activated Akt proteins influence many factors involved in apoptosis, either by transcription regulation or direct phosphorylation.
Protein kinase B (PKB), also known as Akt, is a protein kinase that PLAYS A KEY ROLE in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription and cell migration. Akt regulates cellular survival and metabolism by binding and regulating many downstream effectors.
Aberrant activation of Akt, either via PI3K or independently of PI3K, is often associated with malignancy. Studies have identified gene amplification of the Akt isoforms in many types of cancer, including glioblastoma, ovarian, pancreatic and breast cancers.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599004/

Our data indicate that specific mechanisms have evolved for signalling nodes, like PKB, to select between various downstream events.
Really??!!

Alignment of the subdomains VII and VIII of the kinase domains of Akt family from several organisms revealed
three evolutionarily conserved tyrosine residues Tyr315, Tyr326, and Tyr340, which are close to the activation loop of Akt kinases
http://sci-hub.tw/htt…//www.ncbi.nlm.nih.gov/pubmed/11445557

What does that mean? Conserved means, there was no evolutionary change. It means as well, that the protein cannot work if not in that configuration. zzzz....zzzzz......zzzzzz. It also means, that gradual evolution where each intermediate stage had to be functional would not work.

Akt Signaling Pathway
https://www.thermofisher.com/br/en/home/life-science/antibodies/antibodies-learning-center/antibodies-resource-library/cell-signaling-pathways/akt-signaling-pathway.html

Akt/PKB signaling pathway
https://en.wikipedia.org/wiki/Akt/PKB_signaling_pathway…

Protein kinase B
https://en.wikipedia.org/wiki/Protein_kinase_B#Function

Evolution, or design?

Biological systems demonstrate engineering principles, which point to design

https://reasonandscience.catsboard.com/t2318-gene-regulatory-networks-controlling-body-plan-development#5746

The specific genetic changes that give rise to the evolutionary origins of novel protein-protein interactions have rarely been documented in detail
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0001054

Although numerous investigators assume that the global features of genetic networks are moulded by natural selection, there has been no formal demonstration of the adaptive origin of any genetic network. The mechanisms by which genetic networks become established evolutionarily are far from clear.  Many physicists, engineers and computer scientists, and some cell and developmental biologists, are convinced that biological networks exhibit properties that could only be products of natural selection; however, the matter has rarely been examined in the context of well-established evolutionary principles.  Alon states that it is “…wondrous that the solutions found by evolution have much in common with good engineering,”There is no evidence that genetic pathways emerge de novo in response to a selective challenge.
https://sci-hub.bz/http://www.nature.com/nrg/journal/v8/n10/abs/nrg2192.html

François Jacob pictured evolution as a tinkerer, not an engineer. Engineers and tinkerers arrive at their solutions by very different routes. Rather than planning structures in advance and drawing up blueprints (as an engineer would), evolution as a tinkerer works with odds and ends, assembling interactions until they are good enough to work. It is therefore wondrous that the solutions found by evolution have much in common with good engineering design.
http://science.sciencemag.org/content/301/5641/1866.full

Maybe it's not that wondrous if we consider that the solutions in questions might be explained by the conscious actions of a powerful engineer, namely creator God ?!!

The cell can be viewed as an overlay of at least three types of networks, which describes protein-protein, protein-DNA, and protein-metabolite interactions. Second, biological systems viewed as networks can readily be compared with engineering systems, which are traditionally described by networks such as flow charts and blueprints. Remarkably, when such a comparison is made, biological networks are seen to share structural principles with engineered networks. Here are three of the most important shared principles, modularity, robustness to component tolerances, and use of recurring circuit elements.
http://science.sciencemag.org/content/301/5641/1866.full

The first principle, modularity
is an oft-mentioned property of biological networks. For example, proteins are known to work in slightly overlapping, coregulated groups such as pathways and complexes. Engineered systems also use modules, such as subroutines in software (13) and replaceable parts in machines. The following working definition of a module is proposed based on comparison with engineering: A module in a network is a set of nodes that have strong interactions and a common function. A module has defined input nodes and output nodes that control the interactions with the rest of the network. A module also has internal nodes that do not significantly interact with nodes outside the module. Modules in engineering, and presumably also in biology, have special features that make them easily embedded in almost any system. For example, output nodes should have “low impedance,” so that adding on additional downstream clients should not drain the output to existing clients

The second common feature of engineering and biological networks is robustness to component tolerances.
In both engineering and biology, the design must work under all plausible insults and interferences that come with the inherent properties of the components and the environment. Thus, Escherichia coli needs to be robust with respect to temperature changes over a few tens of degrees, and no circuit in the cell should depend on having precisely 100 copies of protein X and not 103. This point has been made decades ago for developmental systems

The third feature common to engineering and biological networks is the use of recurring circuit elements.
An electronic device, for example, can include thousands of occurrences of circuit elements such as operational amplifiers and memory registers. Biology displays the same principle, using key wiring patterns again and again throughout a network. Metabolic networks use regulatory circuits such as feedback inhibition in many different pathways

Modularity in biological systems

Following article is best read at my library:
https://reasonandscience.catsboard.com/t2672-modularity-in-biological-systems

From molecular to modular cell biology
Nature magazine, 2 DECEMBER 1999
Cellular functions, such as signal transmission, are carried out by ‘modules’ made up of many species of interacting molecules. Although living systems obey the laws of physics and chemistry, the notion of function or purpose differentiates biology from other natural sciences. Function has produced the living cell, with a unique set of properties that distinguish it from inanimate systems of interacting molecules.

Comment: Function is not a creative mechanism. Function is the end result unique set of properties that distinguish it from inanimate systems of interacting molecules.

Cells exist far from thermal equilibrium by harvesting energy from their environment. They are composed of thousands of different types of molecule. They contain information for their survival and reproduction, in the form of their DNA. Their interactions with the environment depend in a byzantine fashion on this information, and the information and the machinery that interprets it are replicated by reproducing the cell. How do these properties emerge from the interactions between the molecules that make up cells. Most biological functions arise from interactions among many components. For example, in the signal transduction system in yeast that converts the detection of a pheromone into the act of mating, there is no single protein responsible for amplifying the input signal provided by the pheromone molecule.

We argue here for the recognition of functional ‘modules’ as a critical level of biological organization. Modules are composed of many types of molecule. They have discrete functions that arise from interactions among their components (proteins, DNA, RNA and small molecules), but these functions cannot easily be predicted by studying the properties of the isolated components.

Have you read this carefully ? Let it sink in for a moment. This sentence advocates basically for Behe's concept of irreducible complexity. The only difference is the different wording.  " Discrete functions ", can be translated to irreducible functions, or irreducible complexity. A certain biological function cannot be achieved by less than certain interactions of components, while these isolated components have no functions by their own. Bingo !!

We believe that general ‘design principles’ — profoundly shaped by the constraints of evolution— govern the structure and function of modules.

Comment: They said right. They believe !! Why not : We believe design principles emanate from an intelligent designer?

Is cell biology modular?
A functional module is, by definition, a discrete entity whose function is separable from those of other modules. This separation depends on chemical isolation, which can originate from spatial localization or from chemical specificity. A ribosome, the module that synthesizes proteins, concentrates the reactions involved in making a polypeptide into a single particle, thus spatially isolating its function. A signal transduction system, on the other hand, such as those that govern chemotaxis in bacteria or mating in yeast, is an extended module that achieves its isolation through the specificity of the initial binding of the chemical signal (for example, chemoattractant or pheromone) to receptor proteins, and of the interactions between signalling proteins within the cell. Modules can be insulated from or connected to each other. Insulation allows the cell to carry out many diverse reactions without cross-talk that would harm the cell, whereas connectivity allows one function to influence another.

Are modules real?
Several lines of evidence suggest that they are. Some modules, such as those for protein synthesis, DNA replication, glycolysis, and even parts of the mitotic spindle (the cellular machinery that ensures the correct distribution
of chromosomes at cell division), have been successfully reconstituted in vitro.

Most functional properties of a module are collective properties, arising from the properties of the underlying components and their interactions.

There is no function for most individual proteins. But joined in an interdependent manner, underlying components and their interactions confer function collectively to a highly ordered, complex, machine-like module. In other words: There is only function for an individual protein as discrete part of a biological module.

Cells contain from millions to a few copies of each of thousands of different components, each with very specific interactions. In biology each of the components is often a microscopic device in itself, able to transduce energy and
work far from equilibrium.

In our opinion, the most effective language to describe functional modules and their interactions will be derived from the synthetic sciences, such as computer science or engineering, in which function appears naturally.

Comment: No. Specific functions are the goal, and engineering and computer science are the methods to reach the goal.

The essence of computational science is the capacity to engineer circuits that transform information from one form into another on the basis of a set of rules. How might the lessons learned here apply to biology? Evolution selects those members of a genetically diverse population whose descendants proliferate rapidly and survive over many generations. One way of ensuring long-term survival is to use information about the current environment to predict
possible future environments and generate responses that maximize the chance of survival and reproduction. This process is a computation, in which the inputs are environmental measurements, the outputs are signals that modulate behaviour, and the rules generate the outputs from the environmental inputs.

Comment: The author is moving goalposts, ignoring entirely the fact that transforming information from one form into another on the basis of a set of rules is essentially a mental process, which has never been observed to emerge spontaneously without conscient intelligent guidance. Evolution is a totally inadequate explanation. And the authors do not address what they should but rather move goalposts to population genetics.

The properties of a module’s components and molecular connections between them are analogous to the circuit diagram of an electrical device.

Comment: In most cases, modules also have no function, unless interconnected with other modules. So a goal or advantage of survival is only achieved when following things are right:

- selection of the right building blocks
- order  and assemble them into functional molecules
- production of protein subunits
- assembly of all subunits to get functional holoenzymes and proteins
- mechanisms to direct these proteins to the right place
- assembly into functional modules
- instructions to create metabolic networks, where the modules are connected to a functional whole
- creation of different cells
- assembly of these differentiated cells into tissues
- assembly of tissues into organs
- assembly of organs into organisms

Biological systems are built and organized in a modular manner, and in various hierarchies, starting from genetics to protein structure, and biological networks of modular partitioning of the geometry of biological space. The question is how these structures could have emerged. Naturalism proposes spontaneous organization to a structured form. But are evolutionary mechanisms, and in case of the structures for life to begin, random events of chemical reactions giving rise to highly organized and complex structures sufficient?  Science-based on secular foundation has a huge task to explain how biology nucleated from among the many possibilities in chemistry.

A number of the design principles of biological systems are familiar to engineers. Positive feedback loops can drive rapid transitions between two different stable states of a system, and negative feedback loops can maintain an output parameter within a narrow range, despite widely fluctuating input. Coincidence detection systems require two or more events to occur simultaneously. In order to activate an output. Amplifiers are built to minimize noise relative to signal, for instance by choosing appropriate time constants for the circuits. Parallel circuits (fail-safe systems) allow an electronic device to survive failures in one of the circuits.

Designs such as these are common in biology.
For example, one set of positive feedback loops drives cells rapidly into mitosis, and another makes the exit from mitosis a rapid and irreversible event16. Negative feedback in bacterial chemotaxis allows the sensory system to detect subtle variations in an input signal whose absolute size can vary by several orders of magnitude.

Coincidence detection lies at the heart of much of the control of gene transcription in eukaryotes, in which the promoters that regulate gene transcription must commonly be occupied by several different protein transcriptions factors before a messenger RNA can be produced. Signal transduction systems would be expected to have their characteristic rate constants set so as to reject chance fluctuations, or noise, in the input signal. DNA replication involves a fail-safe system of error correction, with proofreading by the DNA polymerase backed up by a mismatch repair process that removes incorrect bases after the polymerase has moved on. A failure in either process still allows cells to make viable progeny, but simultaneous failure of both is lethal.

In both biological and man-made systems, reducing the frequency of failure often requires an enormous increase in the complexity of circuits. Reducing the frequency at which individual cells give rise to cancer to about 10–15 has required human cells to evolve multiple systems for preventing mutations that could generate cancer cells, and for killing cells that have an increased tendency to proliferate.

Biological systems can both resist and exploit random fluctuations, or noise. Thus, evolutionary adaptation depends on DNA being mutable, but because most mutations are neutral or deleterious, the rate of mutation is under rigorous genetic control.

The emergence of modular organization of biological structure is described as a symmetry-breaking phase transition, with modularity as the order parameter.  1

In the natural world, one often finds modular, hierarchical structures. Metabolic Networks, Gene Networks, and Protein-Protein Interaction Networks are often modularly built. We can find modularity, and it has been observed in all parts of biology on scales from proteins and genes, to cells, to organs, to ecosystems.   The advantage of modularity is commonly employed in engineering. The claim of secular science is that biological systems are not designed, but supposedly shaped by evolution. Explaining the evolutionary emergence of modularity has however been a challenge, and so far no consensus has been reached. Modular subsystems arrange and connect into networks. Proteins are often made up of almost independent modules. Topological analysis of networks of genes or proteins has revealed modularity as well. Motifs and modules have been found in transcriptional regulation networks, and modules have been found across all scales in metabolic networks. Animal body plans can also be decomposed into clear structural or functional units. Food webs also show compartmentalization. Thus, a hierarchy of modules can be observed that spans many scales of biology.

Many theories have been proposed to explain how and under which conditions modularity emerges.

The question is if natural selection, genetic drift, or gene flow, can account for modularity. Genes have only purpose when they can encode sufficient instructions and the necessary amount of useful information required to make all protein subunits required for a holoenzyme or protein, with all cofactors and co-enzymes, which fulfill specific functions in a biological system. A fully operational and functional protein or holoenzyme confers only function when inserted in a higher biological system.

Theories based on the naturalistic framework try to explain the emergence of modularity through direct or indirect fitness benefits such as enhanced evolvability, facilitated horizontal gene transfer, or improved robustness, or hypothesize that a changing environment selects for adaptable frameworks, and that competition among different evolutionary frameworks leads to selection of structures with the most efficient dynamics, which are the modular ones.
Most neutral theories for the emergence of modularity have focused on the idea of duplication. If parts of a system are duplicated, the result will be more modular than the original system.

This sounds all very "sciency", but cannot hide the fact that these explanations do not address the core of the problem. Modules have only function and purpose in an integrated network, where various submodules contribute to a system that confers only function when all modules are in place, and correctly interconnected. Irreducible and interdependent structures extend in all biology and challenge commonly proposed evolutionary explanations. They seem profoundly inadequate.  A certain threshold of complexity and system completeness is required to change from a state of affairs of functionless to a functional system, and pre-vision of the functional goal is essential.   Another challenge is the fact that often certain functions are reached by either a) convergent evolution, or b) different mechanisms and routes which is another challenge for evolutionary hypotheses.

Modularity and Dynamics of Cellular Networks 3
December 29, 2006
Many phenotypes and behaviors cannot be attributed to isolated components. Rather, they arise from characteristics of cellular networks, which represent connections between molecules in cells. Unlike random networks, cellular networks contain characteristic topological patterns that enable their functionality. The components of cellular networks, including proteins, DNA, and other molecules, act in concert to carry out biological processes. These functionally related components often interact with one another, forming modules in cellular networks. Modules are bigger building units that exhibit a certain functional autonomy. Modules may contain motifs as their structural components. Modules may maintain certain properties such as robustness to environmental perturbations and evolutionary conservations. Modularity exists in a variety of biological contexts, including protein complexes, metabolic pathways, signaling pathways, and transcriptional programs. For transcriptional programs, modules are defined as sets of genes controlled by the same set of TFs under certain conditions . Motifs and modules are also found in protein–protein interaction (PPI) networks and metabolic networks, which may be indicative of multi-subunit protein complexes or members of metabolic pathways. For these networks, modules can be defined as subnetworks whose components' entities (e.g., proteins or metabolites) are more likely to be connected to each other than to entities outside the subnetworks.

Is Modularity a Pre-Requisite for Evolvability? 4
January 22, 2014
Information precedes evolution rather than arising out of it. If modularity enables evolvability, what happens before the modularity? Where did the modularity originally come from? This is the core of intelligent design – that information and its similar entities are requirements of evolution, not products of it.

The transcription factor code - another epigenetic language comes to light

Genes are like a book, which contains the instructions, blueprints, and manuals to make the workhorses of the Cell, proteins, amongst many other things. Proteins have to be produced at the right time, and that depends on the availability of food sources, environmental conditions, and ontology ( development of the organism )

Membrane proteins on the surface of cell membranes transmit the information received from the outside to signalling networks and signal transduction cascades, which are connected to the nucleus, and to chromatin. Cellular signalling cascades regulate the activity of transcription factors that convert extracellular information into gene regulation. The information received is interpreted and directs gene expression.

The right cell response relies upon the expression of the correct genes amongst 20 thousand genes in humans, and the cell machinery has to find the right ones. How does it achieve this feat?

As an analogy, let's suppose someone has to find a book in a library, amongst 20 thousand books. Of course, we use the alphabet or numbers, to tag each book with a short code, and inform the library classification software. In an easy click, the book can be found. But if a functional library classification system had to be invented, and no alphabetical or numerical code would exist? How could a gradual evolutionary development come up with such informational system?   One simpler alternative ( nonetheless far beyond what natural mechanisms could do ) would be to tag each book with an individual sign. So we would require 20 thousand different signs, one for each book. Not very practical, indeed.

The cell faces the same problem. The selective expression of any one of the 20 thousand human genes is accomplished primarily through the interaction of proteins called transcription factors. The binding of a set of such factors ( TFs) acts as a molecular switch for the activation of RNA polymerase and other components of the transcriptional machinery.

Gene expression is controlled by binding of a TF to a regulatory region in DNA, or Cis-regulatory module (CRM). TFs that bind to Cis-regulatory module (CRM) DNA sequences are responsible for either positively or negatively influencing the transcription of specific genes, essentially determining whether a particular gene will be turned "on" or "off" in an organism. ( Equivalent of either picking a book in the shelf of the library, or keep it there )

Much of the complexity in differentiation in animal and plant cells can be attributed to elaborate systems made up of short (6 to 8 base pair) cis-regulatory DNA sequences or motifs, as well as the TFs that bind to the motifs, interact with each other to form complexes and recruit RNA polymerase II. ( That would be equivalent of an autonomous library book retrieval system able to read and recognize the tag on each book, and take the right book out of the shelf ).   TFs generally bind to these specific DNA sequences. Their affinity for these target sequences is roughly one million times higher than their affinity for any other DNA sequence.

In order for an automated library book retrieval and classification system to work, there must be

1. All books in the library tagged
2. All books stored at the right place in the library section and shelf
3. An operational library classification system and software, and the information where to find each book
4. Automated, programmed robots with recognition software, able to direct themselves to the right place and retrieve the book, and make it ready to be read.

in cells, the same organization has to be fully setup right from the start. If one item is missing, nothing goes.

1. All genes with promoter regions and stop signs
2. All genes organized in the right order
3. An operational gene regulatory network, able to respond to external stimuli, food resources, and development
4. Signal transduction cascades, Chromatin, Transcription factors with binding sites that are able to recognize promoter regions in the genome, and bind to them, and activate the transcription machinery.

If each TF protein would have to be coded for by the expression of another gene, which would, in turn, require another protein transcription factor and so on, that would lead to an infinite regress.
However, if a set of proteins is involved, then different combinations can be used for different genes. Thus a smaller number of regulatory proteins can control a large number of genes.

The transcription factor Code
Usually, a combination of several (as many as six) transcription factors is necessary to form a transcription complex which can harness and activate the RNA polymerase to initiate transcription at the right starting point. If a set of proteins is involved, then different combinations can be used for different genes. Thus a smaller number of regulatory proteins can control a large number of genes.

In addition, this provides the means for multiple control at the level of the gene, which has the advantage that transcription may be regulated in a quantitative rather than in an all-or-none manner, and also for producing a network of interacting genes, since the protein product of one gene can affect the expression of another. So one has a combinatorial principle at work here operating at the level of a combination of proteins. In the case of zinc finger proteins, the principle also operates within individual proteins, where different subdomains can be combined to give greater variety or precision of recognition-a microcosm, as it were, of the macroscopic picture.

Multiple TFs can accumulate, creating a bulk the size of a ribosome. Once bound together, changes to the functional domains of a TF and/or covalent interactions with other factors can turn transcription on or off, depending on whether they allow or prohibit the recruitment of RNA polymerase. Two TFs bound at sites near one another on the DNA strand can combine to form a dimer and bend the DNA in what is believed to be part of the activation process.  Some TFs are believed to act as tethering elements between distant enhancers and promoters by forming connections with other proteins.

Combinatorial interactions among transcription factors (TFs) are critical for integrating diverse intrinsic and extrinsic signals, fine-tuning regulatory output and increasing the robustness and plasticity of regulatory systems. In higher eukaryotes, transcription factors (TFs) rarely operate by themselves, but rather directly or indirectly interact with specific partner TFs or chromatin regulators when binding to enhancers. It has been estimated that roughly 75% of all metazoan TFs heterodimerize with other factors

A group of Broad scientists has found that TFs' binding sites within enhancers cluster in distinct patterns reflecting the factors' roles in gene expression control. These patterns may constitute a position-based code. The TF clusters may constitute a general regulatory code, with different cell types substituting specific TFs to activate different sets of enhancers.

There is more.

Post-translational modification code for transcription factors
Post-translational modification PTMs can involve covalently linking chemical groups, lipids, carbohydrates or (poly)peptide chains to amino acids of the target protein during or after its translation. Cellular responses to environmental or physiological cues rely on transduction pathways that must ensure discrimination between different signals. These cascades ‘crosstalk’ and lead to a combinatorial regulation. This often results in different combinations of posttranslational modifications (PTMs) on target proteins, which might act as a molecular barcode. A PTM code is necessary in the context of transcription factors regulating multiple processes. Thus, the coding potential of PTM combinations should both provide a further layer of information integration from several transduction pathways and warrant highly specific cellular outputs.

This is pretty amazing. Evolution, or design? You decide.  

More:
Transcription factors (TF)
https://reasonandscience.catsboard.com/t2738-transcription-factors-tf

Pastafarian dies and arrives at the heavens gate. He is interviewed by the Archangel Gabriel.

G: Hi. Where are you from?
P: The Netherlands
G: Your religion ?
P: Pastafarian
G: Who is your God?
P: The Flying Spaghetti monster
G: We have no God here in heaven with this name
P: Hum... But we have been recognized in our country as a legal religion, and were permitted to celebrate the FSM
G: Sorry, but your God is not here
P: Hum....i know. Our God was just fictional. A Satyre to the institutional Gods.
G: So there is your answer. We have only the real God behind the gates of heaven. Only who became a family member of the God celebrated here, has a free pass.
P: Hum.. ahem... really??! Well.... I want a free pass too.
G: Sorry. Too late, If you did not come with clean clothes, and became a family member on earth, you can't get it. Your clothes are totally dirty
P: That's too bad.... Is there nothing I can do about that? Clean them?
G: Too late. You made fun on earth about our God. Now you cannot change anything. Your eternal fate is sealed.
P: Starts going on its knees, trembling and crying.... please please.... I repent. I want to get in.
G: Your name is not in the book of life. My God does not know you.
P: So what will happen to me now?
G: You will be judged upon what you did on earth, and your eternal destination will be sealed.
P: Please please!! I repent. I know, i should not have made fun of God, I repent !!!
G: Too late. You belong to the cowards, the unbelieving, the vile, the murderers, the sexually immoral, those who practice magic arts, the idolaters and all liars— you will be consigned to the fiery lake of burning sulfur. This is the second death.”

How Systems Biology consolidates the inference of Creationism

https://reasonandscience.catsboard.com/t2061p150-my-articles#6334

From the year 2000 onwards, a new branch of biology, a concept called systems biology, has begun to be used widely in biology in a variety of contexts. The term systems biology was created by Bertalanffy in 1928.  Systems biology focuses on complex interactions in biological systems by applying a holistic perspective. Altogether, this kind of thinking has led to the identification of ideas behind data processing in machines, such as silicon computers, but also created a bridge and inter-related approaches to the architecture and complex structuration of biological systems in nature. Cells and organisms work based on data flow. Data processing can be found in nature all down to the atomic and molecular level. Examples are DNA information storage and the histone code. Moreover, cells have the potential to compute ( process data), both intracellular (e.g. transcription networks) and during cell to cell communication. Higher order cell systems such as the immune and the endocrine system, the homeostasis system, and the nerve system can be described as computational systems. The most powerful biological computer we know is the human brain.

The brain is a " Uber-Computer " - far more sophisticated that man-made computers
https://reasonandscience.catsboard.com/t2736-the-brain-is-a-uber-computer-far-more-sophisticated-that-man-made-computers

Plato introduced in his dialogue Philebus a concept called System. A system is according to Plato a model for thinking about how complex structures are developed. Another idealistic philosopher, Kant, introduced, in 1790, in his Critique of Judgment the concept of self-organizing. Idealistic concepts based systemics have become important in contemporary science in order to understand complexity and big data problems. 9 Cybernetics explains complex systems that exist of a large number of interacting and interrelated parts.

It is a revolutionary paradigm shift in scientific thinking and has also major implications in regards to historical sciences, and the elucidation of origins of life, and biological diversity. Nature and computers are words that used to mean unrelated things. However, this view has changed with this scientific paradigm shift towards systems biology. One of the aims of systems biology is to model and discover properties of cells, tissues and organisms functioning as a system whose theoretical description is only possible using techniques of systems biology. These typically involve metabolic networks or cell signalling networks. As a field of study, particularly, the study of the interactions between the components of biological systems, and how these interactions give rise to the function and behaviour of that system (for example, the enzymes and metabolites in a metabolic pathway or the heart beats). Much effort has been made to elucidate the function of most of the biomolecular components and many of the interactions but that alone does not offer concepts or methods to understand how biological systems work holistically. The pluralism of causes and effects in biological networks is better addressed by observing, through quantitative measures, multiple components simultaneously and by rigorous data integration with mathematical models. 8 Such inquiry can also give answers to how such systems could have emerged.

DNA is a blueprint to produce, amongst other things, proteins - molecular machines, which are discrete units, components of complex biological systems that are useful only in the completion of organismal subcomponents like organs, or organisms as a functional whole.  The development gene regulatory network (dGRN) is like a central processing unit (CPU) the electronic circuitry within a computer that carries out the instructions of a computer program by performing the basic arithmetic, logic, controlling and input/output (I/O) operations specified by the instructions. It is like the control unit that orchestrates the fetching (from memory) and execution of instructions by directing the coordinated operations of the arithmetic logic unit (ALU).

In most—if not all—animals, the multicellular state is established in each generation through serial divisions of the zygote, where daughter cells produced by these divisions become an independent and fully specialized cell type. This functional specialization occurs largely during development and involves the tight coordination of cell proliferation, cell differentiation, tissue growth, and developmental genetic programs. Genes encoding transcription factors and signaling molecules are critical controllers of pattern formation and cell fate specification during development.  Notably, most of these genes are highly conserved across animals (i.e., metazoans) and even their closest unicellular relatives. This striking level of conservation suggests that cell types and animal body plans are, at least partially, controlled by the regulatory capacities of these highly conserved genes. Yet, we cannot help but be intrigued by how such a conserved set of genes with few examples of gene expansions and little changes in their functionality can lead to the vast diversity of cell types and body plan forms found in animals. Transcription factors and signalling molecules participate in multiple, independent developmental processes.

Where Do Complex Organisms Come From?

https://reasonandscience.catsboard.com/t2316-where-do-complex-organisms-come-from

To understand the major trends in animal diversity and if the various kinds of morphology are due to evolution, we must first understand how animal form is generated. As science has unravelled, the make of body form, phenotype, and organismal architecture is due to several genetic and principally, epigenetic interlocked and interconnected mechanisms. The modern, extended evolutionary synthesis does not take into consideration all relevant factors. Structuralism proposes that complex structure emerges holistically from the dynamic interaction of all parts of an organism. It denies that biological complexity can be reduced to natural selection, gene drift and gene flow, and argues that pattern formation is driven principally by multilevel processes that involve various functional units, working in an interdependent manner, pre-programmed to respond to ecological and environmental cues and conditions, food resource availability, and development programs.  Various genetic and epigenetic Codes, an integrated understanding of the structural and functional aspects of epigenetics and several signalling pathways, nuclear architecture during differentiation, chromatin organisation, morphogenetic fields, amongst many other mechanisms.

Transmembrane proteins
https://reasonandscience.catsboard.com/t2398-how-cell-membrane-proteins-point-to-the-requirement-of-planning-intelligence-and-design-for-their-biosynthesis-specific-function-and-insertion-in-the-cell-membrane

Signalling pathways:
http://reasonandscience.heavenforum.org/t2351-the-essential-signaling-pathways-for-animal-development

The Gene regulation network
https://reasonandscience.catsboard.com/t2194-control-of-gene-expression-and-gene-regulatory-networks-point-to-intelligent-design

Epigenetic Codes
https://reasonandscience.catsboard.com/t2213-the-various-codes-in-the-cell

Chromatin dance in the nucleus through extensile motors
https://reasonandscience.catsboard.com/t2746-chromatin-dance-in-the-nucleus-through-extensile-motors-contribute-to-another-higher-order-promoting-gene-regulation-and-expression-design-or-evolution

Post-transcriptional modifications (PTMs) of histones
https://reasonandscience.catsboard.com/t2727-post-transcriptional-modifications-ptms-of-histones-affect-gene-transcription

Chromatin remodeling
https://reasonandscience.catsboard.com/t2726-chromatin-remodeling

The transcription factor Code
https://reasonandscience.catsboard.com/t2738-transcription-factors-tf

The DNA methylation code and language
https://reasonandscience.catsboard.com/t2725-the-dna-methylation-code-and-language

Homeobox and Hox Genes
https://reasonandscience.catsboard.com/t2590p25-origins-what-cause-explains-best-our-existence-and-why#6167

" Junk DNA "
https://reasonandscience.catsboard.com/t2359-how-junk-dna-confirms-intelligent-design-predictions

Transposons and Retrotransposons
https://reasonandscience.catsboard.com/t2393-transposons-and-retrotransposons

Centrosomes
https://reasonandscience.catsboard.com/t2090-centriole-biogenesis-and-the-duplication-cycle-amazing-evidence-of-design

Cytoskeletal arrays
https://reasonandscience.catsboard.com/t2096-the-astonishing-language-written-on-microtubules-amazing-evidence-of-design

Signaling between cells orients the mitotic spindle
https://reasonandscience.catsboard.com/t2383-how-signaling-between-cells-can-orient-a-mitotic-spindle

Ion Channels and Electromagnetic Fields
https://reasonandscience.catsboard.com/t2293-the-recent-groundbreaking-scientific-research-which-explains-the-real-mechanisms-of-biodiversity

The Sugar Code
https://reasonandscience.catsboard.com/t2071-carbohydrates-and-glycobiology-the-3rd-alphabet-of-life-after-dna-and-proteins

Many, once they learned what Christ did for them on the Cross, surrendered, did repent, received forgiveness and grace, keep going on, asking, what else God can do in their daily lives, and pray to receive ongoing blessings. Nothing wrong with that. God says we shall ask. It is part of our relationship with God. We are sustained by him, through him, and every breath is due to his provision. We depend in its entirety on Gods grace and sustaining. But HE has also decided to build HIS body, HIS church, not only through supernatural intervention and revelation and but by using every one of us. You. Me. He has equipped the members of the church with wisdom and HIS spirit to evangelize our neighbour. You're next. To be a good husband or wife. Or patron. Or employee. To be just and loving as he is.

There is one big problem with atheism: It provides no answers.

The one thing the human mind is incapable of comprehending is its self. Anything at all that matters, in life, only does so as a consequence of its impact on conscious brains

Genesis 2:7 Then the LORD God formed a man from the dust of the ground and breathed into his nostrils the breath of life, and the man became a living being.

What an incredibly semantically meaningful sentence.

Only the belief in the Christian God provides intellectually satisfying answers, peace of mind, and peace of the spirit

Evolution, adaptation, homeostasis, and the essential preprogrammed processes essential for life to survive in a changing environment 

Microevolution is better described as adaptation and is an engineered process, which does not happen by accident. The Cell receives macroscopic signals from the environment and responds by adaptive, nonrandom mutations. The capacity of Mammals and other multicellular organisms to adapt to changing environmental conditions is extraordinary.  In order to effectively produce and secrete mature proteins, cellular mechanisms for monitoring the environment are essential. Exposure of cells to various environments causes accumulation of unfolded proteins and results in the activation of a well-orchestrated set of pathways during a phenomenon known as the unfolded protein response (UPR). Cells have powerful quality control networks consisting of chaperones and proteases that cooperate to monitor the folding states of proteins and to remove misfolded conformers through either refolding or degradation. Free-living organisms, which are more directly exposed to environmental fluctuations, must often survive even harsher folding stresses. These stresses not only disrupt the folding of newly synthesized proteins but can also cause misfolding of already folded proteins.  In living organisms, robustness is provided by homeostatic mechanisms. At least five epigenetic mechanisms are responsible for these life-essential processes :

- heat shock factors (HSFs)
- The unfolded protein response (UPR)
- nonhomologous end-joining and homologous recombination
- The DNA Damage Response
- The Response to Oxidative Stress

The cell modulates the signalling pathways at transcriptional, post-transcriptional and post-translational levels. Complex signalling pathways contribute to the maintenance of systemic homeostasis. Homeostasis is the mechanistic fundament of living organisms. 

Homeostasis, from the Greek words for "same" and "steady," refers to any process that living things use to actively maintain fairly stable conditions necessary for survival. It is also synonymous with robustness and adaptability.

This essential characteristic of living cells, homeostasis, is the ability to maintain a steady and more-or-less constant chemical balance in a changing environment. Cell survival requires appropriate proportions of molecular oxygen and various antioxidants. Reactive products of oxygen, calles Reactive Oxygen Species ( ROS) are amongst the most potent and omnipresent threats faced by cells. Cells, damaged by ROS, irreversibly infected, functionless and/or potentially oncogenic cells are destined for persistent inactivation or elimination, respectively. If mechanisms that do not trigger controlled and programmed Cell death ( apoptosis) are not present at day 1, the organisms cannot survive and dies. Simply put, the principle is that all of a multicellular organism's cells are prepared to suicide when needed for the benefit of the organism as a whole. They eliminate themselves in a very carefully programmed way so as to minimize damage to the larger organism.  On average, in human adults, it’s about 50-70 BILLION cells that die per day. We shed 30,000 to 50,000 skin cells every minute.

1. The control of metabolism is a fundamental requirement for all life, with perturbations of metabolic homeostasis underpinning numerous disease-associated pathologies.
2. Any incomplete Metabolic network without the control mechanisms in place to get homeostasis would mean disease and cell death.
3. A minimal metabolic network and the control mechanisms had to be in place from the beginning, which means, and gradualistic explanation of the origin of biological Cells, and life is unrealistic. 
Life is an all or nothing business and points to a creative act of God.

Following  molecules must stay in a finely tuned order and balance for life to survive:
- Halogens like chlorine, fluoride, iodine, and bromine.  The body needs to maintain a delicate balance between all these elements.
- Molybdenum (Mo) and iron (Fe) are essential micronutrients required for crucial enzyme activities and mutually impact their homeostasis, which means, they are interdependent on each other to maintain homeostatic levels. 
- Potassium plays a key role in maintaining cell function, and it is important in maintaining fluid and electrolyte balance. Potassium-40 is probably the most dangerous light radioactive isotope, yet the one most essential to life. Its abundance must be balanced on a razor’s edge.
- The ability of cells to maintain a large gradient of calcium across their outer membrane is universal. All biological cells have a low cytosolic (liquid found inside Cells ) calcium concentration, can and must keep this even when the free calcium outside is up to 20,000 times higher concentrated! 
- Nutrient uptake and homeostasis must be adjusted to the needs of the organisms according to developmental stages and environmental conditions.
- Magnesium is the second most abundant cellular cation after potassium. The concentrations are essential to regulate numerous cellular functions and enzymes
- Iron is required for the survival of most organisms, including bacteria, plants, and humans. Its homeostasis in mammals must be fine-tuned to avoid iron deficiency with a reduced oxygen transport 
- Phosphate, as a cellular energy currency, essentially drives most biochemical reactions defining living organisms, and thus its homeostasis must be tightly regulated. 
- Zinc (Zn) is an essential heavy metal that is incorporated into a number of human Zn metalloproteins. Zn plays important roles in nucleic acid metabolism, cell replication, and tissue repair and growth. Zn contributes to intracellular metal homeostasis. 
- Selenium homeostasis and antioxidant selenoproteins in the brain: lack of finetuned balance has implications for disorders in the central nervous system
- Copper ion homeostasis is maintained through regulated expression of genes involved in copper ion uptake. 

In the early 1960s, Ernest Nagel and Carl Hempel showed that self-regulated systems are teleological.

In his book: THE TINKERER’S ACCOMPLICE, How Design Emerges from Life Itself  J . SCOTT. TURNER, writes at page 12 :
Although I touch upon ID obliquely from time to time, I do so not because I endorse it, but because it is mostly unavoidable. ID theory is essentially warmed-over natural theology, but there is, at its core, a serious point that deserves serious attention. ID theory would like us to believe that some overarching intelligence guides the evolutionary process: to say the least, that is unlikely. Nevertheless, how design arises remains a very real problem in biology.  My thesis is quite simple: organisms are designed not so much because natural selection of particular genes has made them that way, but because agents of homeostasis build them that way. These agents’ modus operandi is to construct environments upon which the precarious and dynamic stability that is homeostasis can be imposed, and design is the result.

The author does not identify these agents, but Wiki describes agents as CONSCIOUS beings, which act with specific goals in mind. In the case of life, this agent made it possible for biological cells to actively maintain fairly stable levels of various metabolites and molecules, necessary for survival. We are once more, upon careful examination of the evidence in nature, justified to infer an intelligent designer as most case-adequate explanation of the origin of homeostasis and the ability of adaptation, commonly called evolution, of all living organisms.  

Theist: Kalaam
Atheist: Debunked a long time ago
T: Fine-tuning
A. The weak anthropic principle refutes the argument
T: Abiogenesis doesn't work
A. Urey- Miller & hydrothermal vents
T: Macroevolution has never been observed
A: We have fossils, evolution is a fact.
T: Objective moral values can only come from God
A: God is a monster
T: What would convince you God exists?
A: I just reject Theistic beliefs
T: So what would convince you God exists?
A: We replace God with honesty by saying "we don't know". The fact that we don't currently know does not mean we will never know because we have science, the best method we have for answering questions about things we don't know. Simply saying "God did it" is making up an answer because we are too lazy to try to figure out the real truth.

Catch22 Origin of Life problems - checkmake for Abiogenesis

Lynn Margulis:
To go from a bacterium to people is less of a step than to go from a mixture of amino acids to a bacterium.

This is very true. But we can go a step further:

To go from the existence of the basic building blocks on early earth to Cell assembly of complex carbohydrates, lipids, proteins, nucleic acids, metals and seven non-metal elements from monomers is less of a step than to go from the existence of these small organic molecules synthesized in Cells to a fully working self-replicating Cell. This might be surprising, but not when someone knows the efforts taken by cells to synthesize these building blocks, which is truly remarkable.

One of the most dramatic evidence why abiogenesis fails is the fact that to make these basic building blocks of life, the cell machinery which is made upon these very basic building blocks must be fully set up and operating. That creates a catch22 situation:

It takes Proteins to make the basic building blocks of life. But it takes the basic building blocks of life to make proteins.
It takes ATP to make proteins. But it takes proteins to make ATP ( the energy currency of the cell).
It takes proteins to make amino acids ( the monomers that make proteins ). But it takes amino acids to make proteins
It takes DNA to make proteins. But it takes proteins to make DNA ( a great number of the cell machinery is actually employed to make DNA).
It takes proteins to make RNA. But it takes RNA to make proteins
It takes proteins to go from RNA to DNA.
It takes RNA and DNA to make proteins that turn RNA into DNA
It takes signalling networks to produce the right rate of products required in the cell
It takes these products to construct signalling networks
It takes Glutamate synthetase proteins ( veritable molecular computers ) to sense the right rate of nitrogen uptake, required in the cell.
It takes nitrogen to make Glutamate synthetase proteins

should I go on !?

Cell duplication and DNA replication is essential for the survival and perpetuation of all living things. It takes over 30 specialized irreducible proteins for DNA replication. But it takes the DNA to RNA transcription and RNA translation to make proteins. What came first?
It takes proteins to make the error-check and correction proteins that reduce the DNA replication error rate 10.000.000.000 times. These error check and correction proteins had to be checked too. How did the process start?
But it takes the DNA transcription and translation to make proteins. What came first?
It takes a fully setup signalling network for cells to adapt to ecological variations, like heat-shock proteins to adapt to climate variation and temperatures. How did that system start, if it is non-functional, if not fully setup?
It takes fully synthesized Fe/S ( Iron sulphur) clusters for a majority of proteins used in oxidation-reduction reactions, essential for all life forms. But it takes complex uptake and synthesis processes to make these metal clusters through veritable nano-molecular non-ribosomal peptide synthetase (NRPS) assembly lines for iron uptake. What came first: These manufacturing assembly lines, or the proteins that make them?
The central metabolic pathways like glycolysis or the Citric Acid cycle are essential to make Adenine triphosphate ( ATP ),  the energy currency in the cell, and amino acids, the basic building blocks of proteins. These metabolic pathways use enzymes, which are made through ATP and amino acids. How did these pathways emerge?
It takes DNA and proteins to make phospholipids for Cell membranes. But the Cell membrane must be fully setup and permit a closed, protected environment, for the very own processes to operate that synthesize Cell membranes.
The Lipid membrane would be useless without membrane proteins but how could membrane proteins have emerged in the absence of functional membranes?

Carbohydrates are metabolized to provide energy and are stored in muscle and liver as glycogen. Six-carbon glucose molecules are degraded by a series of chemical reactions to three-carbon pyruvate by the reactions of glycolysis; pyruvate.  The core structure of the metabolic network is very similar across all organisms. Centrally located within this network are the sugar-phosphate reactions of glycolysis and the pentose phosphate pathway. Together with the overlapping reactions of the Entner–Doudoroff pathway and of the Calvin cycle, they provide the precursor metabolites required for the synthesis of RNA, DNA, lipids, energy and redox coenzymes and amino acids—key molecules required for life.

Cells use hierarchical levels of organization, where the function and proper set up of the higher level depend on the lower level. And that lower level, as shown above, depends on irreducible biochemical synthesis processes. That is an all or nothing business, which could not be setup if not by intelligent setup.

Abiogenesis is a mount insurmountable - by all means.

Biological Cells are a self-replicating factory with the ability of self-replication of the entire factory once ready, to respond to changing environmental demands and regulate its metabolic pathways, regulate and coordinate all cellular processes, such as molecule and building block biosynthesis according to the cells demands, depending on growth, and other factors. The ability of uptake of nutrients, to be structured, internally compartmentalized and organized, being able to check replication errors and minimize them, and react to stimuli, and changing environments. That's is, the ability to adapt to the environment is a must right from the beginning. If just ONE single protein or enzyme - of many - is missing, no life. The study below lists functional annotation descriptions ( proteins, enzymes). If just ONE of these 561 is missing, no life. If topoisomerase II or helicase are missing - no replication - no perpetuation of life. Let us suppose a fortunate accident would sort out, amongst over 500 known different types of amino acids, the 20 types, used for life. Not only would it have to select the right ones amongst these over 500 amino acids which can exist and come in two configurations -  left, and right-handed chiral directions. They would have to be joined somehow to the same assembly site on early earth in sufficient quantities. The availability of these amino acids would have to be synchronized so that at some point, either individually or in combination, they are all available at the same time. The selected parts must all be made available at the same ‘construction site,’ perhaps not simultaneously but certainly, at the time, they are needed.

Once there, each protein with an average of about 300 amino acids would have to be produced, each with its individual specific function. At least 561 of the right, life essential proteins. Each complementary to the others, in right shape and size, able to interact with others like lock and key. The individual proteins had to be mutually compatible, that is, ‘well-matched’ and capable of properly ‘interacting’: even if subsystems or parts are put together in the right order, they also need to interface correctly. If they are not joined together in a functional manner, no deal. Nothing will go. The parts must be coordinated in just the right way: even if all of the parts of a system are available at the right time, it is clear that the majority of ways of assembling them will be non-functional or irrelevant.

As a comparison: Imagine a print machine. If it had 561 parts, each had to be produced individually and then assembled together. If the cartridge is not extant, the printer cannot work. Same with biological Cells. Another major hurdle is, if there is no energy source, the printer won't work. Same with biological Cells. While we can plug an energy cable into a socket and connect the printer to an energy source, there was non-available on a prebiotic earth. Cells use extremely complex metabolic pathways to produce their energy in form of ATP.

So, somehow, early earth produced these 561 complementary proteins.  And if there is no energy in form of ATP molecules to drive each protein through phosphorylation, nothing goes. So besides these proteins, ATP would have had to be around, ready to do its job. The problem is: It takes ATP to make proteins. But it takes proteins to make ATP. What came first? Another major problem would be - these polypeptides would be exposed to UV radiation,      ( there was no protective UV shield yet on the atmosphere ), so rather than stabilize, they would disintegrate quickly.  All this would have had to happen by self-assembly, spontaneously by orderly aggregation and sequentially correct manner without external direction.

In Cells, fermentation is a very slow process to make ATP. In bacteria and eukaryotes, the production of ATP is done through the central metabolism pathways, but they yield only a small quantity of ATP. The major producers are ATP synthase, veritable nano turbines, another marvel, one of the most amazing molecular machines. And if they are not coupled to a proton gradient, which requires other complex proteins which create it, no deal. And if there are no mechanisms to produce the molecules used as burning fuel like glucose to drive the process of proton gradient formation, no deal either.  

Cells use complex molecular machines and EXTREMELY complex multistep pathways to synthesize each of these 20 amino acids, and enzymes measure and sensor with feedback loops precisely the rate of amino acids that are required of each AA type like a computer, and produces the right quantity, accordingly. And in order to economize energy, it recycles used proteins. Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds, and so, amino-acids are recycled, which is an enormous economy of energy expenditure to synthesize new proteins. Amino acids come from keto acids and other compounds in the Reductive Tricarboxylic Acid (rTCA) Cycle, a central metabolic pathway in all life forms. The problem here again is another catch22. It takes nine complex proteins of the reverse Citric Acid Cycle to fix carbon and make it available for the production of the carbon backbone of amino acids. But it takes this process to make the proteins and enzymes required in the Reductive Tricarboxylic Acid (rTCA) Cycle. We have only considered the make of amino acids, not taking in consideration, that to make the other basic building blocks of life, namely RNA, DNA, hydrocarbons and fatty acids, each constitutes in other catch22 situations.

So the problem of the arrangement of the right amino acid sequence to make just one protein is the least of all problems that origin of life research faces, they are so many, that we can say with confidence: Abiogenesis is a no-no.

A minimal estimate for the gene content of the last universal common ancestor
19 December 2005
A truly minimal estimate of the gene content of the last universal common ancestor, obtained by three different tree construction methods and the inclusion or not of eukaryotes (in total, there are 669 ortholog families distributed in 561 functional annotation descriptions ( proteins, enzymes) , including 52 which remain uncharacterized) This set of 669/561 sequence/function categories can be considered as the truly minimal estimate for the gene content of LUCA. LUCA  does not appear dramatically different from extant life

Minimal  gene content of the first biological cell = 561 functional annotation descriptions = that means, it cannot be reduced further = irreducibly complex

- Replication/recombination/repair/modification
- Transcription/regulation
- transslation/ribosome
- RNA processing
- cell division
- thermoprotection
- signaling
- proteolysis
- Transport/membrane
- Electron transport
- Metabolism

The gene content of the last universal common ancestor (LUCA) with respect to DNA processing (replication, recombination, modification and repair) contains a wide range of functions. The following families/functions are identified:

- DNA polymerase
- excinuclease ABC
- DNA gyrase
- topoisomerase
- NADdependent DNA ligase
- DNA helicases
- mismatch repair MutS  and MutT
- endonucleases, RecA
- chromosome segregation SMC
- methyltransferase, methyladenine

I have not enough faith to believe in non-guided mechanisms to explain the origin of life. Do you?

The Cellular internet network:
Multicellular organisms have a sophisticated  internet-like communication system and cargo delivery service, all in one

- The setup and implementation of sophisticated, complex and advanced communication networks like the internet depend on the invention of highly intelligent, skilled communication network engineers.
- Multicellular organisms use several extremely advanced communication systems, like Tunneling nanotubes (TNT's),  Extracellular Vesicles ( VT's) which are, on top of that, also cargo carriers ( there are, furthermore, cell-cell gap junctions and exosomes ). The size of the communication and cargo delivery network of the human body is 75 thousand times the size of the entire internet of the whole world, if there would be just one communication connection between each cell ( in reality, things are far more complex: each neuron cell computer is connected  up to 10,000 other neurons )
- This is amazing evidence that multicellular organisms and their communication systems were definitively created by an extremely intelligent designer.

Imagine the internet not only as a world wide web for an interchange of information and communication but also a courier delivery service carrier of goods, like FedEx. That would be pretty convenient, wouldn't it?

In 2018, there are an estimate of 4 billion computers connected through the internet, worldwide.  Most recent data estimates the number of human Cells to 3.0·10^13.  If we put that each cell uses just one communication channel to interact with other cells, then the size of the communication and cargo delivery network of the human body would be 75 thousand times the size of the world wide web !!

When biting into an apple, the body will immediately signal a complex sequence of messages and processes to break down the apple into energy and essential structural nutrients for cellular repair and replacement. That initial signal activates communication throughout the entire body, enabling metabolism to send support to every facet of the organisms function, be it mental, emotional or physical. Health and performance are completely dependent upon how efficient that signalling and communication process works.  

Cell-Cell interactions are performed in multicellular organisms through a sophisticated intercellular communication machinery. There are many ways like gap junctions and exosomes. But recently, it has been discovered that Cells talk and help each other via tiny tube networks. Cells are known to use intracellular microtubules, veritable nanotubular highways which direct proteins to their correct final destination inside of Cells. But, remarkably they are also used for intercellular communication, from Cells to Cells, and furthermore, for organelle Transport between Cells.

In 2004, for the first time, Hans-Hermann Gerdes as a researcher at EMBL Germany reported novel cell-to-cell communication channels that he called tunnelling nanotubes. They are thin tube structures which protruding from one cell and connecting with another to form a nanotubular network with the surrounding cells. These intercellular bridges are not empty membrane tubes but filled with cytoskeletal filaments, like actin, microtubules and motor proteins.

Tunnelling nanotubes (TNT's) and other bridges between cells act as conduits for sharing RNA, proteins or even whole organelles. These cryptic conduits between cells, long tubes in mammalian cells, transport not just molecular signals but much larger cargo, such as viral particles, prions or even mitochondria, the cell's energy-generating structures. They transfer all kinds of cargo, microRNAs, including messenger RNAs, proteins, viruses and even whole organelles, such as lysosomes. Moreover, ions like calcium (Ca2+) and different proteins lipid components of the membrane have all been identified to have the ability to cross TNTs in various cell types. Moreover, the latest findings demonstrate functional roles in physiological and pathological processes, such as signal transduction, micro and nano-particles delivery, immune responses, embryogenesis, cellular reprogramming, and apoptosis.  They are a critical requirement for development, and tissue homeostasis and regeneration. Recent studies have been shown the important role of TNTs in mechanical and signalling processes during embryonic patterning and development. ATP and motor protein kinesin, dynein and myosin are required for the cargo transfer by TNTs.

Interestingly, gap junctions, as an important cell-to-cell communication for electrical conductivity and Ca2+flux, were found to have a role in TNT-mediated Ca2+transfer between cells. TNT's associated with gap junctions were shown to support the bi-directional spread of electrical signals, leading to the activation of low-voltage-gated Ca2+channels in the coupling cell. Electrical synchronization between distant cells through TNTs leads to activation of downstream target signalling. The results of different studies implicate the importance of electrical signalling in control cell behaviour and developmental processes, such as the establishment of left-right pattern in embryos, tail regeneration of Xenopus, and wound healing. Electrical signalling is important in embryogenesis.TNT's associated with gap junctions induce bi-directional spread of electrical signals between cells.

TNT-mediated communication can induce immune responses in target cells. They have as well an essential role in mechanical and signalling processes during embryonic patterning and development and a significant role in vertebrate gastrulation. They mediate the transfer of proteins between distant cells.

These observations demonstrate an awe-inspiring level of sophisticated connectivity between cells.  

These fragile structures are appearing in normal embryonic development. And stressed or ailing cells induce them by sending out signals to call for help. It’s unclear yet, though, how healthy cells sense that their neighbours need help or how they physiologically “know” what specific cargo to send.

To make things even more remarkable, TNT form among several cell types, including neuronal cells, epithelial cells, and almost all immune cells.  There are many different types of cells which are able to communicate using TNTs, and their functions are impressive. In myeloid cells (e.g., macrophages, dendritic cells, and osteoclasts), intercellular communication via TNT contributes to their differentiation and immune functions. Importantly, TNT enables myeloid cells to communicate with a targeted neighbouring or distant cell, as well as with other cell types, therefore creating a complex variety of cellular communication and cargo exchanges. TNT mediate even long-range communication, independent of soluble factors. They are membranous structures displaying a remarkable capacity to communicate with selected neighbour or distant cells.

It has also been reported TNTs can contribute to cellular differentiation and reprogramming by providing a highway to transfer cellular components from one cell to a target cell.

Moreover, if TNTs are akin to skywalks, the enclosed footbridges that connect separate buildings, then gap junctions — gated pores that pass through the membranes of neighbouring cells — are like doorways between adjacent rooms. Exosomes, small vesicles shed by cells, were long thought to be cellular trash bags carrying debris, but scientists now recognize them as vehicles for carrying microRNAs and other signalling molecules between cells, sometimes over long distances.

Cells use different means of biological communication and signal transduction constituting direct physical contact between cells such as receptor-mediated interaction or cellular junctions between neighbouring cells. Receptor-mediated cellular interactions are facilitated by certain transmembrane proteins and cell adhesion molecules such as integrins, tetraspanins, and cadherins. The direct coupling of the cytoplasm of two cells through gap junctions (GJs) and concomitant transport of cytoplasmic material is also considered essential process in cellular cross-talk and is important for maintaining tissue homeostasis, development, and cellular differentiation.

In the absence of direct physical contact, cells may convey biological messages in paracrine fashion through secreted factors such as cytokines, chemokines, and secreted growth factors.

Cell-to-cell communication is a critical requirement to coordinate behaviours of the cells in a community and thereby achieve tissue homeostasis and conservation of the multicellular organisms. Tunnelling nanotubes (TNTs), as a cell-to-cell communication over long distance, allow for bi- or uni-directional transfer of cellular components between cells. During the last decade, research has shown TNTs have different structural and functional properties, varying between and within cell systems.

Direct cell-to-cell communication is a critical requirement for development, tissue regeneration and conservation of normal physiology of multicellular organisms. Plants share their cytoplasmic contents through intercellular channels called plasmodesmata, whereas animal cells possess analogous gap junctions and tunnelling nanotubes (TNTs)

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