Cell biology Information Intelligent Design

At Quanta: Cells find “optimal” solutions, not just good ones

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structure of an animal cell/royroydeb (CC BY-SA 4.0)

We are told that cells’s ability hints at “a more general principle of life”:

The same precision and reproducibility emerge from a sea of noise again and again in a range of cellular processes. That mounting evidence is leading some biologists to a bold hypothesis: that where information is concerned, cells might often find solutions to life’s challenges that are not just good but optimal — that cells extract as much useful information from their complex surroundings as is theoretically possible. Questions about optimal decoding, according to Aleksandra Walczak, a biophysicist at the École Normale Supérieure in Paris, “are everywhere in biology.”Jordana Cepelewicz, “The Math That Tells Cells What They Are” at Quanta

What then becomes of “bad design” arguments, like those of Nathan Lents? In a transient world, any solution can only be optimal for a given life, as it must be factored against other lives.

Before you go: In Nature: Cells have “secret conversations” We say this a lot: That’s a lot of information to have simply come into being by natural selection acting on random mutation (Darwinism). It’s getting not only ridiculous but obviously ridiculous.

Researchers: Helpful gut microbes send messages to their hosts If the strategy is clearly identified, they should look for non-helpful microbes that have found a way to copy it (horizontal gene transfer?)

Cells and proteins use sugars to talk to one another Cells are like Neanderthal man. They get smarter every time we run into them. And just think, it all just tumbled into existence by natural selection acting on random mutations (Darwinism) too…

Researchers: First animal cell was not simple; it could “transdifferentiate” From the paper: “… these analyses offer no support for the homology of sponge choanocytes and choanoflagellates, nor for the view that the first multicellular animals were simple balls of cells with limited capacity to differentiate.”

“Interspecies communication” strategy between gut bacteria and mammalian hosts’ genes described

Researchers: Cells Have A Repair Crew That Fixes Local Leaks

Researchers: How The Immune System “Thinks”

Follow UD News at Twitter!

Researcher: Mathematics Sheds Light On “Unfathomably Complex” Cellular Thinking

How do cells in the body know where they are supposed to be?

Researchers A Kill Cancer Code Is Embedded in Every Cell

33 Replies to “At Quanta: Cells find “optimal” solutions, not just good ones

  1. 1
    bornagain77 says:

    Hmmm, in the article they themselves concede that,,

    ,,, while evolutionary theory suggests that evolving systems can improve over time, nothing guarantees that they should be driven to an optimal level.

    ,, and also concede that,,

    “How the cells do it remains a mystery. Right now, “the whole thing is kind of wonderful and magical,”

    Yet despite those rather startling concessions they, none-the-less, still hold that,,,

    “Through evolution, these cells have figured out how to implement Bayes’ trick using regulatory DNA.”

    Well contrary to their self-admitted unwarranted presupposition that this ‘optimal positional information’ is somehow encoded by Darwinian evolution within the cell itself, we now have compelling evidence that this ‘optimal positional information’ is coming into the developing embryo ‘from the outside’.
    At about the 41:00 minute mark of the following video, Dr. Wells, using a branch of mathematics called category theory, demonstrates that, during embryological development, information must somehow be added to the developing embryo, ‘from the outside’, by some ‘non-material’ method.

    Design Beyond DNA: A Conversation with Dr. Jonathan Wells – video (41:00 minute mark) – January 2017
    https://youtu.be/ASAaANVBoiE?t=2484

    The following article adds weight to Dr Wells assessment and states: “the process of development should be thought of as being controlled by an “algebraic structure outside space-time itself”

    Intelligent Design and the Advancement of Science – Brian Miller – December 11, 2017
    Excerpt: DNA was expected to be the primary source of causality behind the operation and development of life. Such beliefs have previously raised concerns from leading scientists and mathematicians. For instance, physicist Walter Elsasser argued that the unfathomable complexity of the chemical and physically processes in life was “transcomputational” — beyond the realm of any theoretical means of computation. Moreover, the development of the embryo is not solely directed by DNA. Instead, it requires new “biotonic” principles. As a result, life cannot be reduced to chemistry and physics. An unbridgeable gap separates life from non-life.
    Similarly, mathematician René Thom argued that the 3D patterns of tissues in an organism’s development from egg to birth and their continuous transformation cannot be understood in terms of isolating the individual proteins generated by DNA and other molecules produced in cells. The problem is that the individual “parts” composing tissues and organs only take on the right form and function in the environment of those tissues and organs. More recent work by Denis Noble further has elucidated how every level of the biological hierarchy affects every other level, from DNA to tissues to the entire organism. Based partly on these insights, Thom concluded in his book Structural Stability and Morphogenesis that the process of development should be thought of as being controlled by an “algebraic structure outside space-time itself” (p. 119). Likewise, Robert Rosen argued that life can only be understood as a mathematical abstraction consisting of functional relationships, irreducible to mechanistic processes. He observed that life is fundamentally different from simple physics and chemistry. It embodies the Aristotelian category of final causation, which is closely related to the idea of purpose. The conclusions of these scholars challenge materialistic philosophy at its core.
    https://evolutionnews.org/2017/12/intelligent-design-and-the-advancement-of-science/

    To provide further evidence for information coming into the developing embryo from ‘outside space-time itself’, it is also important to note that quantum correlations somehow arise from outside spacetime, in the sense that no story in space and time can describe them,,,

    Looking beyond space and time to cope with quantum theory – 29 October 2012
    Excerpt: “Our result gives weight to the idea that quantum correlations somehow arise from outside spacetime, in the sense that no story in space and time can describe them,”
    http://www.quantumlah.org/high.....uences.php

    And these quantum correlations which somehow arise from outside spacetime, are now found in molecular biology on a massive scale. In every DNA and Protein molecule,,,

    “What happens is this classical information (of DNA) is embedded, sandwiched, into the quantum information (of DNA). And most likely this classical information is never accessed because it is inside all the quantum information. You can only access the quantum information or the electron clouds and the protons. So mathematically you can describe that as a quantum/classical state.”
    Elisabeth Rieper – Classical and Quantum Information in DNA – video (Longitudinal Quantum Information resides along the entire length of DNA discussed at the 19:30 minute mark; at 24:00 minute mark Dr Rieper remarks that practically the whole DNA molecule can be viewed as quantum information with classical information embedded within it)
    https://youtu.be/2nqHOnVTxJE?t=1176

    Classical and Quantum Information Channels in Protein Chain – Dj. Koruga, A. Tomi?, Z. Ratkaj, L. Matija – 2006
    Abstract: Investigation of the properties of peptide plane in protein chain from both classical and quantum approach is presented. We calculated interatomic force constants for peptide plane and hydrogen bonds between peptide planes in protein chain. On the basis of force constants, displacements of each atom in peptide plane, and time of action we found that the value of the peptide plane action is close to the Planck constant. This indicates that peptide plane from the energy viewpoint possesses synergetic classical/quantum properties. Consideration of peptide planes in protein chain from information viewpoint also shows that protein chain possesses classical and quantum properties. So, it appears that protein chain behaves as a triple dual system: (1) structural – amino acids and peptide planes, (2) energy – classical and quantum state, and (3) information – classical and quantum coding. Based on experimental facts of protein chain, we proposed from the structure-energy-information viewpoint its synergetic code system.
    http://www.scientific.net/MSF.518.491

    Quantum criticality in a wide range of important biomolecules – Mar. 6, 2015
    Excerpt: “Most of the molecules taking part actively in biochemical processes are tuned exactly to the transition point and are critical conductors,” they say.
    That’s a discovery that is as important as it is unexpected. “These findings suggest an entirely new and universal mechanism of conductance in biology very different from the one used in electrical circuits.”
    The permutations of possible energy levels of biomolecules is huge so the possibility of finding even one (biomolecule) that is in the quantum critical state by accident is mind-bogglingly small and, to all intents and purposes, impossible.,, of the order of 10^-50 of possible small biomolecules and even less for proteins,”,,,
    “what exactly is the advantage that criticality confers?”
    https://medium.com/the-physics-arxiv-blog/the-origin-of-life-and-the-hidden-role-of-quantum-criticality-ca4707924552

    Moreover, the following article points out that the unresolved enigma of protein folding, that is to say, the unresolved enigma for how a protein might achieve its basic 3-dimensional form, can be easily explained if the process of folding is a quantum affair.

    Physicists Discover Quantum Law of Protein Folding – February 22, 2011
    Quantum mechanics finally explains why protein folding depends on temperature in such a strange way.
    Excerpt: First, a little background on protein folding. Proteins are long chains of amino acids that become biologically active only when they fold into specific, highly complex shapes. The puzzle is how proteins do this so quickly when they have so many possible configurations to choose from.
    To put this in perspective, a relatively small protein of only 100 amino acids can take some 10^100 different configurations. If it tried these shapes at the rate of 100 billion a second, it would take longer than the age of the universe to find the correct one. Just how these molecules do the job in nanoseconds, nobody knows.,,,
    Today, Luo and Lo say these curves can be easily explained if the process of folding is a quantum affair. By conventional thinking, a chain of amino acids can only change from one shape to another by mechanically passing through various shapes in between.
    But Luo and Lo say that if this process were a quantum one, the shape could change by quantum transition, meaning that the protein could ‘jump’ from one shape to another without necessarily forming the shapes in between.,,,
    Their astonishing result is that this quantum transition model fits the folding curves of 15 different proteins and even explains the difference in folding and unfolding rates of the same proteins.
    That’s a significant breakthrough. Luo and Lo’s equations amount to the first universal laws of protein folding. That’s the equivalent in biology to something like the thermodynamic laws in physics.
    http://www.technologyreview.co.....f-protein/

  2. 2
    bornagain77 says:

    The amount of ‘optimal positional information’ coming into the developing embryo, ‘from the outside’, is enormous. As Dr. Doug Axe states in the following video at the 1 hour 16 minute mark, “there are a quadrillion neural connections in the human brain, that’s vastly more neural connections in the human brain than there are bits (of information) in the human genome. So,,, there’s got to be something else going on that makes us what we are.”

    “There is also a presumption, typically when we talk about our genome, (that the genome) is a blueprint for making us. And that is actually not a proven fact in biology. That is an assumption. And (one) that I question because I don’t think that 4 billion bases, which would be 8 billion bits of information, that you would actually have enough information to specify a human being. If you consider for example that there are a quadrillion neural connections in the human brain, that’s vastly more neural connections in the human brain than there are bits (of information) in the human genome. So,,, there’s got to be something else going on that makes us what we are.”
    Doug Axe – Intelligent Design 3.0 – Stephen C. Meyer – video
    https://youtu.be/lgs6J4LqeqI?t=4575

    And in the following video, it is noted that the information to build a human infant, atom by atom, would take up the equivalent of enough thumb drives to fill the Titanic, multiplied by 2,000.

    In a TED Talk, (the Question You May Not Ask,,, Where did the information come from?) – November 29, 2017
    Excerpt: Sabatini is charming.,,, he deploys some memorable images. He points out that the information to build a human infant, atom by atom, would take up the equivalent of enough thumb drives to fill the Titanic, multiplied by 2,000. Later he wheels out the entire genome, in printed form, of a human being,,,,:
    [F]or the first time in history, this is the genome of a specific human, printed page-by-page, letter-by-letter: 262,000 pages of information, 450 kilograms.,,,
    https://evolutionnews.org/2017/11/in-a-ted-talk-heres-the-question-you-may-not-ask/

    The following video states that “There are 10^28 atoms in the human body.,, The amount of data contained in the whole human,, is 3.02 x 10^32 gigabytes of information. Using a high bandwidth transfer, that data would take about 4.5 x 10^18 years to teleport 1 time. That is 350,000 times the age of the universe.”

    Will Teleportation Ever Be Possible? – video – 2013
    https://youtu.be/yfePpMTbFYY?t=76
    Quote from video:
    “There are 10^28 atoms in the human body.,, The amount of data contained in the whole human,, is 3.02 x 10^32 gigabytes of information. Using a high bandwidth transfer that data would take about 4.5 x 10^18 years to teleport 1 time. That is 350,000 times the age of the universe.”

    Moreover, in quantum mechanics it is information that is primarily conserved, not necessarily matter and energy that are primarily conserved, as matter and energy are primarily conserved in classical (Darwinian) mechanics. As the following article states, ‘In the classical world, information can be copied and deleted at will. In the quantum world, however, the conservation of quantum information means that information cannot be created nor destroyed.’

    Quantum no-hiding theorem experimentally confirmed for first time – 2011
    Excerpt: In the classical world, information can be copied and deleted at will. In the quantum world, however, the conservation of quantum information means that information cannot be created nor destroyed. This concept stems from two fundamental theorems of quantum mechanics: the no-cloning theorem and the no-deleting theorem. A third and related theorem, called the no-hiding theorem, addresses information loss in the quantum world. According to the no-hiding theorem, if information is missing from one system (which may happen when the system interacts with the environment), then the information is simply residing somewhere else in the Universe; in other words, the missing information cannot be hidden in the correlations between a system and its environment.
    http://www.physorg.com/news/20.....tally.html

    Besides quantum information providing direct empirical falsification of neo-Darwinian claims that say that information in life must be ’emergent’ from some material basis, the implication of finding ‘non-local’, beyond space and time, and ‘conserved’, quantum information in molecular biology on such a massive scale, is fairly, and pleasantly, obvious.
    That pleasant implication, or course, being the fact that we now have direct physical evidence strongly indicating that we do indeed have an eternal transcendent soul that is capable of living beyond the death of our material bodies.
    As Stuart Hameroff notes in this following video, “the quantum information,, isn’t destroyed. It can’t be destroyed.,,, it’s possible that this quantum information can exist outside the body. Perhaps indefinitely as a soul.”

    “Let’s say the heart stops beating. The blood stops flowing. The microtubules lose their quantum state. But the quantum information, which is in the microtubules, isn’t destroyed. It can’t be destroyed. It just distributes and dissipates to the universe at large. If a patient is resuscitated, revived, this quantum information can go back into the microtubules and the patient says, “I had a near death experience. I saw a white light. I saw a tunnel. I saw my dead relatives.,,” Now if they’re not revived and the patient dies, then it’s possible that this quantum information can exist outside the body. Perhaps indefinitely as a soul.”
    – Stuart Hameroff – Quantum Entangled Consciousness – Life After Death – video (5:00 minute mark)
    https://youtu.be/jjpEc98o_Oo?t=300

    And as Jesus asked,

    Mark 8:37
    Is anything worth more than your soul?

    Thus in conclusion, the ‘bottom up’ reductive materialistic framework of Darwinian evolution is found to be grossly inadequate, especially when considering ‘positional information’, for explaining how any particular organism might achieve its basic form.

    Darwinism vs Biological Form – video
    https://www.youtube.com/watch?v=JyNzNPgjM4w

    Moreover, to state what should be glaringly obvious, since neo-Darwinian explanations are grossly inadequate for explaining how any particular organism might achieve its basic form, then neo-Darwinian speculations for how one type of organism might transform into another type of organism are based on pure fantasy and have no discernible experimental basis in reality.
    Whereas, on the other hand, Theism, especially with these recent breakthroughs in quantum biology,,,

    Darwinian Materialism vs Quantum Biology – video
    https://www.youtube.com/watch?v=LHdD2Am1g5Y

    ,,,is found to be very well supported in its claim that God has formed each of us in our mother’s womb.

    Verses:

    Psalm 139:13-14
    For You formed my inward parts;
    You covered me in my mother’s womb.
    I will praise You, for I am fearfully and wonderfully made;
    Marvelous are Your works,
    And that my soul knows very well.

    Jeremiah 1:5
    “Before I formed you in the womb I knew you, before you were born I set you apart; I appointed you as a prophet to the nations.”

  3. 3
    PeterA says:

    BA77,
    Excellent posts. Thanks

  4. 4
    OLV says:

    The proneural wave in the Drosophila optic lobe is driven by an excitable reaction-diffusion mechanism
    David J Jörg, Elizabeth E Caygill, […], and Benjamin D Simons
    eLife. 2019; 8: e40919.
    doi: 10.7554/eLife.40919

    In living organisms, self-organised waves of signalling activity propagate spatiotemporal information within tissues.

    this ‘proneural wave’ is driven by an excitable reaction-diffusion system involving epidermal growth factor receptor (EGFR) signalling interacting with the proneural gene l’sc.

    The development of multicellular organisms relies on a multitude of transient coordination processes that provide the spatiotemporal cues for cell fate decision-making and thereby ensure that tissues are specified with the correct size, pattern and composition

    the proneural wave involves the activation of an excitatory pulse of signalling activity and gene expression, giving rise to a tightly-regulated propagating transition zone.

    such a mechanism may serve more widely as a generic and robust strategy to achieve sequential transition waves in developing tissues.

  5. 5
    OLV says:

    Mathematical modeling of movement on fitness landscapes
    Nishant Gerald, Dibyendu Dutta, R. G. Brajesh and Supreet SainiEmail author
    BMC Systems Biology
    DOI: 10.1186/s12918-019-0704-0

    exponential or normal distributions can statistically approximate the distribution of mutational effects to a satisfactory degree. This is especially true when the starting fitness corresponding to a particular set is low (compared to the peak permissible fitness). What distribution of a parameter value in its prescribed range results in an exponential or a normal distribution, however, remains an open question.

  6. 6
    OLV says:

    Overcoming the Cost of Positive Autoregulation by Accelerating the Response with a Coupled Negative Feedback
    Rong Gao and Ann M. Stock
    Cell Rep. 2018 Sep 11; 24(11): 3061–3071.e6.
    doi: 10.1016/j.celrep.2018.08.023

    Cells have […] complex gene regulatory networks to produce appropriate amounts of proteins at appropriate times to adapt to ever-changing environments. A few recurring network motifs, such as feed-forward loops and autoregulatory circuits, constitute the basic building blocks for more sophisticated regulatory networks

    A fundamental trade-off between rapid response and optimal expression of genes below cytotoxic levels exists for many signaling circuits, particularly for positively autoregulated systems with an inherent response delay.

    Coupled negative autoregulation is discovered to allow a strong promoter for fast response without incurring cost of increasing protein expression levels.

  7. 7
    OLV says:

    BA 77:

    “the ‘bottom up’ reductive materialistic framework of Darwinian evolution is found to be grossly inadequate, especially when considering ‘positional information’, for explaining how any particular organism might achieve its basic form.”

    Yes. Well stated.

  8. 8
    OLV says:

    Overcoming the Cost of Positive Autoregulation by Accelerating the Response with a Coupled Negative Feedback
    Rong Gao and Ann M. Stock
    Cell Rep. 2018 Sep 11; 24(11): 3061–3071.e6.
    doi: 10.1016/j.celrep.2018.08.023

    “…the effectiveness of such a regulatory strategy […] to circumvent the trade-off between response speed and expression level.”

    This strategy offers great flexibility in fine-tuning the response speed as well as the expression level.

    It remains to be explored how many TFs share the mechanism […] to reconcile different fitness requirements.

    another yet unknown negative feedback may operate in the engineered system.

  9. 9
    OLV says:

    Mechanisms of Spindle Positioning: Lessons from Worms and Mammalian Cells
    Sachin Kotak
    Biomolecules 2019, 9(2), 80; doi:10.3390/biom9020080

    Proper positioning of the mitotic spindle is fundamental for specifying the site for cleavage furrow, and thus regulates the appropriate sizes and accurate distribution of the cell fate determinants in the resulting daughter cells during development and in the stem cells.

    how the abovementioned components precisely and spatiotemporally regulate spindle positioning by sensing the physicochemical environment for execution of flawless mitosis.

    To efficiently grow and divide, all cells undergo a series of tightly regulated events known as the cell cycle. In eukaryotes, the cell cycle comprises Interphase and M-phase. M-phase is further divided into mitosis (or meiosis in germ cells) and cytokinesis. During mitosis, all animal cells establish an elegant diamond-shaped microtubule-based structure known as a mitotic spindle that is critical for ensuring error-free partitioning of the genomic, as well as intracellular contents

    the accurate positioning of the mitotic spindle is critical for the correct placement of the cleavage furrow, relative sizes and spatial organization of the daughter cells, and faithful segregation of the cell fate determinants during asymmetric cell divisions including in the stem cells

    most of these mechanisms primarily rely on the dynamic astral microtubules that emanate from the centrosomes.

    cells also possess mechanisms whereby they rely on external mechanical signals to instruct the intracellular chemical environment to align the mitotic spindle correctly.

    how this intricate machinery spatiotemporally coordinate with mitotic progression to ensure proper spindle positioning.

    the importance of upstream polarity regulators in guiding spindle positioning

    new paradigms whereby extrinsic physical and chemical signals are shown to modulate spindle positioning

    interesting remaining questions; answering those will be helpful for better understanding the underlying mechanisms of spindle positioning

    The inherent ability of the mitotic spindle to position in the particular reference axis is vital to generate cell fate diversity and to ensure that cells are organized in a proper three-dimensional arrangement within a tissue.

    despite the discovery of several sophisticated building blocks that organize and spatiotemporally control spindle positioning, our understanding how these individual pieces collectively communicate to regulate spindle positioning is still far from clear.

  10. 10
    OLV says:

    Mechanisms of Spindle Positioning: Lessons from Worms and Mammalian Cells
    Sachin Kotak
    Biomolecules 2019, 9(2), 80; doi:10.3390/biom9020080

    it is becoming more apparent that cortical actin and its associated proteins play a crucial role of spindle positioning, but whether these players directly or indirectly affect spindle positioning by modulating the localization/activity of the ternary complex and dynein remains elusive.

    It would be equally important to test if analogous to mammalian cells in culture, whether various mammalian tissues also employ multiple mitotic kinases to fine-tune accurate positioning of their spindle in a spatiotemporal manner.

    how mechanical cues are guiding chemical machinery to orient mitotic spindle is not yet very much evident, and thus new data in this theme will definitely strengthen our current understanding.

    exciting time lie ahead of us where we can expect novel insights in the theme of spatial and temporal regulation of spindle positioning for error-free cell division.

  11. 11
    OLV says:

    Isn’t it really amazing that someone could seriously believe that all the above posted examples of fascinating biological choreographies are the result of natural (unguided) evolutionary processes?

  12. 12
    PaoloV says:

    OLV,

    No, that’s not amazing at all. Actually, it’s written in the Christian Scriptures, which refer to all the people “who by their unrighteousness suppress the truth. For what can be known about God is plain to them, because God has shown it to them. For His invisible attributes, namely, His eternal power and divine nature, have been clearly perceived, ever since the creation of the world, in the things that have been made. So they are without excuse.”
    Romans 1:18-20

    It’s basically our sinful condition that explains our natural rebellious attitude of rejection of the truth.

  13. 13
    PavelU says:

    PaoloV @12:

    Your theological comment is off topic, for this is a purely scientific discussion, as you may see in the OP headline. Note that it clearly shows that the main topic is Cell Biology.

  14. 14
    jawa says:

    PavelU @13,

    Is OLV’s comment @11 also off topic according to your rule?

  15. 15
    PavelU says:

    jawa,

    That’s not my rule. It’s a commonly accepted standard that you should be aware of too.

  16. 16
    PeterA says:

    PavelU @15:

    Did you respond jawa’s question @14?

  17. 17
    PavelU says:

    PeterA @16:

    I corrected jawa’s misunderstanding about “off topic”, which invalidated his question.

  18. 18
    OLV says:

    The dynein adaptor Hook2 plays essential roles in mitotic progression and cytokinesis
    Devashish Dwivedi, Amrita Kumari, […], and Mahak Sharma
    J Cell Biol. 2019 Mar 4; 218(3): 871–894.
    doi: 10.1083/jcb.201804183

    Hook proteins are evolutionarily conserved dynein adaptors that promote assembly of highly processive dynein–dynactin motor complexes. Mammals express three Hook paralogs, namely Hook1, Hook2, and Hook3, that have distinct subcellular localizations and expectedly, distinct cellular functions.

    Hook2 binds to and promotes dynein–dynactin assembly specifically during mitosis. During the late G2 phase, Hook2 mediates dynein–dynactin localization at the nuclear envelope (NE), which is required for centrosome anchoring to the NE. Independent of its binding to dynein, Hook2 regulates microtubule nucleation at the centrosome; accordingly, Hook2-depleted cells have reduced astral microtubules and spindle positioning defects. Besides the centrosome, Hook2 localizes to and recruits dynactin and dynein to the central spindle. Dynactin-dependent targeting of centralspindlin complex to the midzone is abrogated upon Hook2 depletion; accordingly, Hook2 depletion results in cytokinesis failure.

    the zebrafish Hook2 homologue promotes dynein–dynactin association and was essential for zebrafish early development. Together, these results suggest that Hook2 mediates assembly of the dynein–dynactin complex and regulates mitotic progression and cytokinesis.

    In this case gpuccio’s insightful analysis of the involved proteins would have been a delightful treat that is missed here. Are there any detectable information jumps here too? Definitely missing those comments and OPs.

  19. 19
    jawa says:

    PavelU @13:

    Is OLV’s comment @11 also off topic?

    BTW, do you have any objections for BA77’s comments @1 and @2 ? Are they within topic?

  20. 20
    OLV says:

    The dynein adaptor Hook2 plays essential roles in mitotic progression and cytokinesis
    Devashish Dwivedi, Amrita Kumari, […], and Mahak Sharma
    J Cell Biol. 2019 Mar 4; 218(3): 871–894.
    doi: 10.1083/jcb.201804183

    we cannot determine the mechanism underlying dynactin-dependent targeting of the centralspindlin complex to the midzone. To precisely understand the role of dynactin in midzone recruitment of centralspindlin subunits, it would be important in future studies to use targeted approaches of inhibiting dynactin function specifically at the central spindle.

    It would be relevant to determine whether the role of Hook2 as a dynein–dynactin linker is required for endosomal trafficking within the midbody.

  21. 21
    OLV says:

    The dynein adaptor Hook2 plays essential roles in mitotic progression and cytokinesis
    Devashish Dwivedi, Amrita Kumari, […], and Mahak Sharma
    J Cell Biol. 2019 Mar 4; 218(3): 871–894.
    doi: 10.1083/jcb.201804183

    Another important question is to elucidate the precise mechanism by which Hook2 regulates MT nucleation. As centrosomal levels of ?-tubulin were unaffected upon Hook2 depletion, it is possible that Hook2 either directly or indirectly modulates ?-TURC nucleation activity. Future studies would provide new insights into Hook2 function and illuminate the regulatory mechanisms that govern its function as a dynein–dynactin adaptor.

  22. 22
    OLV says:

    Leader of the SAC: molecular mechanisms of Mps1/TTK regulation in mitosis
    Spyridon T. Pachis and Geert J. P. L. Kops
    Open Biol. 2018 Aug; 8(8): 180109.
    doi: 10.1098/rsob.180109

    how localization and activity of the chief executive officer of the SAC, the kinase Mps1, is regulated. Understanding its role in the protection of genome stability is far from complete, however, and several key lacunas need to be filled.

    Very little is known about how and where this pool of Mps1 becomes activated.

    Upon entry into mitosis, Mps1 recruitment to unattached kinetochores is necessary for the wave of activation that is needed to mount a full SAC response. Several questions as to how this is achieved are as yet unanswered. How does dimerization of Mps1 occur and how does it affect the activation dynamics of the kinase? What are the steps leading to full activation of the kinase, and what are the roles of specific NTE and MR modifications?

  23. 23
    OLV says:

    Leader of the SAC: molecular mechanisms of Mps1/TTK regulation in mitosis
    Spyridon T. Pachis and Geert J. P. L. Kops
    Open Biol. 2018 Aug; 8(8): 180109.
    doi: 10.1098/rsob.180109

    The recent finding of a possible inactive ‘prone-to-autophosphorylate’ conformer of Mps1 involving the NTE implies an even more complex activation mechanism than currently envisioned

    How exactly are Aurora B and ARHGEF17 involved in these initial Mps1–kinetochore interactions ?

    Have all contributing factors been identified?

    Oh, no! More complex?

  24. 24
    OLV says:

    Leader of the SAC: molecular mechanisms of Mps1/TTK regulation in mitosis
    Spyridon T. Pachis and Geert J. P. L. Kops
    Open Biol. 2018 Aug; 8(8): 180109.
    doi: 10.1098/rsob.180109

    how exactly does inactivation take place and what are the dynamics of it?

    where this residual Mps1 is binding and how much reduction of Mps1 levels is sufficient to tip the balance in favour of the phosphatases and switch off SAC signalling.

    Elucidating the finer points of Mps1 regulation in the coming years will provide crucial insights into how genomic stability is ensured.

  25. 25
    OLV says:

    Altered Gene Regulatory Networks Are Associated With the Transition From C3 to Crassulacean Acid Metabolism in Erycina (Oncidiinae: Orchidaceae)
    Karolina Heyduk, Michelle Hwang, […], and Jim Leebens-Mack
    Front Plant Sci. 2018; 9: 2000.
    doi: 10.3389/fpls.2018.02000

    the growing evidence suggests that the secondary processes that make a CAM plant, including stomatal regulation, light sensing and downstream transcriptional responses, and carbohydrate metabolism feedbacks, undergo fine-tuning along the evolutionary trajectory between C3 and CAM. Further work that characterizes closely related C3 and CAM species has the potential to greatly advance our understanding of the integration of nighttime CO2 acquisition with more complex regulatory pathways.

    How can that fine-tuning happen?

  26. 26
    OLV says:

    Feather arrays are patterned by interacting signalling and cell density waves
    William K. W. Ho, Lucy Freem, […], and Denis J. Headon,
    PLoS Biol. 2019 Feb; 17(2): e3000132.
    Published online 2019 Feb 21. doi: 10.1371/journal.pbio.3000132

    Feathers are arranged in a precise pattern in avian skin. They first arise during development in a row along the dorsal midline, with rows of new feather buds added sequentially in a spreading wave.

    a reaction-diffusion-taxis system, integrated with mechanical processes, generates the feather array. In flighted birds, the key role of the EDA/Ectodysplasin A receptor (EDAR) pathway in vertebrate skin patterning has been recast to activate this process in a quasi-1-dimensional manner, imposing highly ordered pattern formation.

    the manner of wave loss differs in different species, with ostrich embryos lacking the wave of EDA, whereas the emu lacks sufficient skin cells at the appropriate developmental stage to make precisely organised feather rudiments.

    A number of theoretical mechanisms to explain the spontaneous emergence of periodicity in biological systems have been proposed

    Our present work uncovers a distinct process normally operating in avian skin, in which elements of both reaction-diffusion and cell movement–based patterning systems are integrated into a unified periodicity-generating mechanism.

    In avian skin, we report a hybrid of these conceptual systems, a reaction-diffusion-taxis mechanism integrated with mechanical processes. These local patterning interactions are triggered within the broad field of the skin by the passing of a travelling EDA wave, imposing the construction of a precise hexagonal lattice of feather primordia.

  27. 27
    OLV says:

    Post-Turing tissue pattern formation: Advent of mechanochemistry
    Felix Brinkmann, Moritz Mercker, […], and Anna Marciniak-Czochra
    PLoS Comput Biol. 2018 Jul; 14(7): e1006259.
    doi: 10.1371/journal.pcbi.1006259

    Chemical and mechanical pattern formation is fundamental during embryogenesis and tissue development. Yet, the underlying molecular and cellular mechanisms are still elusive in many cases.

    the main contradictions arising in the framework of purely chemical theories are naturally and automatically resolved using the mechanochemical patterning theory.

    During embryogenesis, biological tissues gradually increase their complexity by self-organised creation of diverse chemical and mechanical patterns. Detailed mechanisms driving and controlling these patterns are not well understood.

    The presented modelling approach can be used to combine simulations with recent experimental developments, to help unravel one of the big mysteries in biology: The mechanisms of self-organised pattern formation during embryogenesis.

    the knowledge about how chemical patterns are produced, controlled, and how they interact with mechanical patterns is still very unsatisfactory.

    this [Turing] theory is not devoid of serious difficulties

    an appropriate candidate for the long-range inhibitor is still missing in many cases

    mechanical cues can be translated in various ways in order to influence and control chemical patterns, leading to the rapidly evolving research area of mechanotransduction in cell biology

    tissue mechanics is increasingly moving into focus to explain features of pattern formation which have been previously ascribed to diffusing molecules according to the Turing theory.

    Notably, forces and flows generated by motor proteins or advection have been proposed to significantly increase diffusion rates for long-range inhibition

    However, a general mechanochemical theory for robust pattern formation is still missing.

    models investigating mechanochemical pattern formation are still rare.

    the presented approach may serve as a future basis of enhance interactions of experiments with simulation methods in order to further unravel one of the big mysteries in development: the self-organised generation of patterns and shapes.

  28. 28
    OLV says:

    Global Computational Biology Market Growth, Trends and Forecast (2019-2024): A $6.79 Billion Opportunity – ResearchAndMarkets.com

    The use of bioinformatics tools in life sciences has become necessary to analyze experimental data. The huge amounts of data pose a challenge for the biological community, as most biologists are not familiar with informatics and statistical interpretation. An interdisciplinary collaboration was started with an aim to address the need for biologists to understand biological data.

  29. 29
    OLV says:

    Detection of Dynamic Spatiotemporal Response to Periodic Chemical Stimulation in a Xenopus Embryonic Tissue
    YongTae Kim, Sagar D. Joshi, […], and Lance A. Davidson
    PLoS One. 2011; 6(1): e14624.
    doi: 10.1371/journal.pone.0014624

    Embryonic development is guided by a complex and integrated set of stimuli that results in collective system-wide organization that is both time and space regulated.

    These regulatory interactions result in the emergence of highly functional units, which are correlated to frequency-modulated stimulation profiles.

    Embryonic development is a complex, dynamic and highly regulated feedback process where cells actively respond to and exert control over their environment to form intact tissues, which results in functioning organ systems

    Gradients of chemical factors drive emergent phenomena in embryos by stimulating cascades of cell signaling, gene regulatory networks, cell motility, and cell differentiation. Together, these cues provide positional information to establish distinct cell identities that self-assemble into functional tissues.

  30. 30
    OLV says:

    A Molecular Tension Sensor for N-Cadherin Reveals Distinct Forms of Mechanosensitive Adhesion Assembly in Adherens and Synaptic Junctions
    Ishaan Puranam, Aarti Urs, Brenna Kirk, Karen Newell-Litwa, Brenton Hoffman
    doi: https://doi.org/10.1101/552802

    N-cadherin tension is subject to cell type specific regulation and mechanosensitive signaling occurs within SJs.

    Within tissues, the primary functions of cell-cell adhesions are to enable structure formation, maintain mechanical integrity, and facilitate signal transmission [1, 2]. These functions require cell-cell adhesions to resist mechanical loads. This is enabled by a variety of sub-cellular structures, such as adherens junctions (AJs) and synaptic junctions (SJs), in different cellular contexts.

    Traditionally, the mechanical integrity of these structures is thought to be mediated by cadherins, a large family of transmembrane proteins with over 100 members [3]. These proteins simultaneously form calcium-dependent adhesive interactions between cells, and link to the stiff actin cytoskeleton through interactions with catenins and a variety of other scaffolding proteins [1, 4].

    However, recent advances in the emerging field of mechanobiology have demonstrated that cell-cell adhesion is not solely mediated by the passive, adhesive interactions of cadherins and other proteins. Instead, tensile forces play a key role in the formation and stabilization of cell-cell adhesions [5-10]. These tensile forces activate mechanosensitive signaling pathways through the alternation of protein conformations and the formation of new protein-protein interactions. Most research has focused on the mechanobiology of AJs formed by epithelial or endothelial cells, which are mediated by the classical cadherins E-cadherin and VE-cadherin, respectively [1, 11].

    Excitingly, these studies are revealing new insights into the mechanical aspects of tissue development, wound healing, and the initiation of mechanosensitive diseases including cancer and atherosclerosis; however, the mechanosensitive roles of the other cadherin family members in various tissue types are not as well understood.

    A key next step will be further elucidating the mechanosensitive signaling pathways activated by the loading of AJs and SJs.

    This may be key to the complex signaling that likely underlies likely complex long-term biological processes, such as synaptic maturation and LTP.

    Notably, the RhoGTPases are also known to be subject to mechanosensitive regulation and play key roles in AJ assembly as well as synapse development. In particular, the regulation of RhoGTPases during LTP consolidation is particularly complex.

    Notably, key regulators of RhoGTPases that preferentially affect each stage of synaptic development, including a variety of GEFs and GAPs as well RhoGDI, have been identified [78]. A major question for future work will be determine if these regulators are subject to mechanosensitive regulation.

    Functional complexity and complex functionality.

  31. 31
    OLV says:

    Calcium as a signal integrator in developing epithelial tissues.
    Brodskiy PA, Zartman JJ.
    Phys Biol. 2018 May 16;15(5):051001.
    doi: 10.1088/1478-3975/aabb18.

    Decoding how tissue properties emerge across multiple spatial and temporal scales from the integration of local signals is a grand challenge in quantitative biology.
    For example, the collective behavior of epithelial cells is critical for shaping developing embryos. Understanding how epithelial cells interpret a diverse range of local signals to coordinate tissue-level processes requires a systems-level understanding of development. Integration of multiple signaling pathways that specify cell signaling information requires second messengers such as calcium ions. Increasingly, specific roles have been uncovered for calcium signaling throughout development.
    Calcium signaling regulates many processes including division, migration, death, and differentiation.
    However, the pleiotropic and ubiquitous nature of calcium signaling implies that many additional functions remain to be discovered.

    Quantitative imaging and computational modeling have provided important insights into how calcium signaling integration occurs.

    Reverse-engineering the conserved features of signal integration mediated by calcium signaling will enable novel approaches in regenerative medicine and synthetic control of morphogenesis.

    many additional functions remain to be discovered?

    Oh, no!

    Reverse-engineering?

    Wow!

    Bottom line: many new papers increasingly make it harder for the “Darwinism of the gaps” to coherently and comprehensively explain things in biology. No surprise that some of their former comrades are desperately jumping off their sinking ship, clinging to anything that appears to float, hoping to get rescued by another passing by ship. 🙂

  32. 32
    OLV says:

    Continuum of Gene-Expression Profiles Provides Spatial Division of Labor within a Differentiated Cell Type
    2019 CELL SYSTEMS Volume: 8, Issue: 1
    Miri Adler, Yael Korem Kohanim, Avichai Tendler, Avi Mayo, Uri Alon
    Weizmann Institute of Science

    Single-cell gene expression reveals the diversity within a differentiated cell type. Often, cells of the same type show a continuum of gene-expression patterns. The origin of such continuum gene-expression patterns is unclear. To address this, we develop a theory to understand how a continuum provides division of labor in a tissue in which cells collectively contribute to several tasks. We find that a continuum is optimal when there are spatial gradients in the tissue that affect the performance in each task. The continuum is bounded inside a polyhedron whose vertices are expression profiles optimal at each task. We test this using single-cell gene expression for intestinal villi and liver hepatocytes, which form a curved 1D trajectory and a full 3D tetrahedron in gene-expression space, respectively. We infer the tasks for both cell types and characterize the spatial zonation of the task-specialist cells. This approach can be generally applied to other tissues.

  33. 33
    OLV says:

    Central dogma rates and the trade-off between precision and economy in gene expression.
    2019 NATURE COMMUNICATIONS Volume: 10, Issue: 1, pp 68-68
    Jean Hausser, Avi Mayo, Leeat Keren, Uri Alon
    Weizmann Institute of Science

    Steady-state protein abundance is set by four rates: transcription, translation, mRNA decay and protein decay. A given protein abundance can be obtained from infinitely many combinations of these rates. This raises the question of whether the natural rates for each gene result from historical accidents, or are there rules that give certain combinations a selective advantage? We address this question using high-throughput measurements in rapidly growing cells from diverse organisms to find that about half of the rate combinations do not exist: genes that combine high transcription with low translation are strongly depleted. This depletion is due to a trade-off between precision and economy: high transcription decreases stochastic fluctuations but increases transcription costs. Our theory quantitatively explains which rate combinations are missing, and predicts the curvature of the fitness function for each gene. It may guide the design of gene circuits with desired expression levels and noise.

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