Mystery at the heart of life

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December 21, 2014

Cell biology, Intelligent Design, News

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Cell biology
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By Biologic Institute’s Ann Gauger, at Christianity Today’s Behemoth, the secret life of cells:

Our bodies are made up of some 100 trillion cells. We tend to think of cells as static, because that’s how they were presented to us in textbooks. In fact, the cell is like the most antic, madcap, crowded (yet fantastically efficient) city you can picture. And at its heart lies a mystery—or I should say, several mysteries—involving three special kinds of molecules: DNA, RNA, and proteins.

These molecules are assembled into long chains called polymers, and are uniquely suited for the roles they play. More importantly, life absolutely depends upon them. We have to have DNA, RNA, and protein all present and active at the same time for a living organism to live.

How they work together so optimally and efficiently is not merely amazing, but also a great enigma, a mystery that lies at the heart of life itself. More. Paywall soon after. May be worth it.

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Although the vermiform appendix is commonly considered a vestigial organ, adverse health consequences after an appendectomy have garnered increasing attention. We found an increased risk of a subsequent gallstone diagnosis within 5 years after an appendectomy. Although the vermiform appendix in humans is commonly considered a vestigial organ, a certain immune function is believed to be involved based on its association with substantial lymphatic tissues.
Increased Risk of Clinically Significant Gallstones following an Appendectomy: A Five-Year Follow-Up Study Shiu-Dong Chung,#1,2,3 Chung-Chien Huang,#4 Herng-Ching Lin,#3,4 Ming-Chieh Tsai,5 and Chao-Hung Chen PLoS One. 11(10): e0165829. doi: 10.1371/journal.pone.0165829

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The gut microbiome is being more widely recognized for its association with positive health outcomes, including those distant to the gastrointestinal system. As the types of prebiotics available diversify, so too will our understanding of the range of microbes able to degrade them, and the extent to which body sites can be impacted by their consumption. The human colon harbours 1011–1012 live microorganisms per gram that, along with those in the small intestine, comprise the gut microbiota. In healthy individuals, this vast community acts symbiotically with the host to improve intestinal integrity, metabolism, and compete against pathogenic organisms. More human clinical trials are needed, particularly longitudinal, that have the power to observe subtle changes over the duration of ingestion, as well as carefully controlled animal studies to explain how these effects occur. Given the success of prebiotics in the attenuation of many diseases and improvement of health at distant sites, these food-grade saccharides are becoming key components of a health-promoting diet.
Distant Site Effects of Ingested Prebiotics Stephanie Collins and Gregor Reid Nutrients. 8(9): 523. doi: 10.3390/nu8090523

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Optimal nutrition early in life is exceptionally important when rapid brain development occurs. In human infants, breast milk is recognized as the optimal form of nutrition due to its many roles in supporting infant growth and development. Some human milk bioactives thought to exert beneficial effects on developing brain such as docosahexaenoic acid (DHA), milk fat globule membrane (MFGM), and lactoferrin have been individually studied, but knowledge of their combined impact is lacking. It is well understood that neuroanatomical development does not progress uniformly across all regions and pathways and that differential maturation contributes to differential development of cognitive capacities. [...] a combination of bioactive ingredients in early life diet can influence structural brain development.
Early life diet containing prebiotics and bioactive whey protein fractions increased dendritic spine density of rat hippocampal neurons. Waworuntu RV, Hanania T, Boikess SR, Rex CS, Berg BM Int J Dev Neurosci. 55:28-33. doi: 10.1016/j.ijdevneu.2016.09.001.

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Microorganisms exhibit a wide range of environmental adaptations and lifestyles encoded by their genomes. The genetic code alone only scratches the surface of complexity in the biological network of a living cell.
Protein Languages Differ Depending on Microorganism Lifestyle Joseph J. Grzymski1,* and Adam G. Marsh PLoS One. 9(5): e96910. doi: 10.1371/journal.pone.0096910

Complex complexityDionisio_{November 29, 2016
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Neurons are highly compartmentalized cells with functionally distinct cytoplasmic/membrane domains (dendrites, axons, and somas), [...] Local mRNA translation mediates the adaptive responses of axons to extrinsic signals [...] [...] intricate regulation of compartment-specific mRNA translation in mammalian CNS axons supports the formation and maintenance of neural circuits in vivo. [...] local protein synthesis regulates synaptic transmission and axon maintenance.
Dynamic Axonal Translation in Developing and Mature Visual Circuits Toshiaki Shigeoka,1,4 Hosung Jung,2,4,5,? Jane Jung,2 Benita Turner-Bridger,1 Jiyeon Ohk,2 Julie Qiaojin Lin,1 Paul S. Amieux,3 and Christine E. Holt1 Cell. 166(1): 181–192. doi: 10.1016/j.cell.2016.05.029

Complex complexityDionisio_{November 29, 2016
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The spinal cord integrates and relays somatosensory input, leading to complex motor responses. Research over the past couple of decades has identified transcription factor networks that function during development to define and instruct the generation of diverse neuronal populations within the spinal cord. A number of studies have now started to connect these developmentally defined populations with their roles in somatosensory circuits. Here, we review our current understanding of how neuronal diversity in the dorsal spinal cord is generated and we discuss the logic underlying how these neurons form the basis of somatosensory circuits.
Making sense out of spinal cord somatosensory development. Lai HC, Seal RP, Johnson JE Development 143: 3434-3448; doi: 10.1242/dev.139592

Complex complexity.Dionisio_{November 29, 2016
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More than a passive effector of gene expression, mRNA translation (protein synthesis) by the ribosome is a rapidly tunable and dynamic molecular mechanism. [...] our understanding of regulation of the ribosome and mRNA translation during normal brain development is only in its early stages. mRNA translation is emerging as a key driver of the rapid and timed regulation of spatiotemporal gene expression in the developing nervous system, including the neocortex. Understanding the multivariate control of mRNA translation by ribosomal complex specificity will be critical to reveal the intricate mechanisms of normal brain development and pathologies of neurodevelopmental disorders.
The frontier of RNA metamorphosis and ribosome signature in neocortical development. Kraushar ML, Popovitchenko T, Volk NL, Rasin MR Int J Dev Neurosci. pii: S0736-5748(16)30004-1. doi: 10.1016/j.ijdevneu.2016.02.003.

Complex complexity.Dionisio_{November 29, 2016
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Surprisingly, we did not observe any NOGGIN induction in [...] This suggests important differences in the inductive rules between vertebrates, and will require further investigations [...] Surprisingly, we found in our system that NOGGIN was critical in positioning fate domains over a wide range of density in our human gastruloids, which strongly suggests a role for NOGGIN in positioning the primitive streak and mesendodermal populations during early human gastrulation. How activators and inhibitors spread between epithelial cells is obscure.
A Balance between Secreted Inhibitors and Edge Sensing Controls Gastruloid Self-Organization. Etoc F, Metzger J, Ruzo A, Kirst C, Yoney A, Ozair MZ, Brivanlou AH, Siggia ED Dev Cell. 39(3):302-315. doi: 10.1016/j.devcel.2016.09.016. http://www.cell.com/developmental-cell/pdf/S1534-5807(16)30638-4.pdf http://www.cell.com/cms/attachment/2072728012/2068550133/mmc2.pdf

Complex complexity.Dionisio_{November 29, 2016
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In some instances, mathematics beyond the usual gene-by-gene differential equations is required to tie together qualitative facts that are intrinsic to development Thus, if one hopes to explain morphogenesis in engineering terms that can be used in a predictive way to guide regenerative medicine, some astute phenomenological descriptions of subprocesses are necessary.
A Balance between Secreted Inhibitors and Edge Sensing Controls Gastruloid Self-Organization. Etoc F, Metzger J, Ruzo A, Kirst C, Yoney A, Ozair MZ, Brivanlou AH, Siggia ED Dev Cell. 39(3):302-315. doi: 10.1016/j.devcel.2016.09.016. http://www.cell.com/developmental-cell/pdf/S1534-5807(16)30638-4.pdf http://www.cell.com/cms/attachment/2072728012/2068550133/mmc2.pdf

Complex complexity.Dionisio_{November 29, 2016
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The earliest aspects of human embryogenesis remain mysterious. Our knowledge about morphogen/inhibitor induction is very limited in mammals. The gastrulating embryo is a remarkable example of a self-organizing system: from a seemingly homogeneous epiblast layer, cells are allocated into the three germ layers as the body plan unfolds. There is a complex interplay between geometry and signaling.
A Balance between Secreted Inhibitors and Edge Sensing Controls Gastruloid Self-Organization. Etoc F, Metzger J, Ruzo A, Kirst C, Yoney A, Ozair MZ, Brivanlou AH, Siggia ED Dev Cell. 39(3):302-315. doi: 10.1016/j.devcel.2016.09.016. http://www.cell.com/developmental-cell/pdf/S1534-5807(16)30638-4.pdf http://www.cell.com/cms/attachment/2072728012/2068550133/mmc2.pdf

Complex complexity.Dionisio_{November 29, 2016
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[...] investigators are now frequently observing that the complexity of structural order emerging in cultures of PPSCs and MPSCs can be astonishing. Whether a blastocyst possesses specific patterning information for axis formation and positioning/shaping of a PS [...] and how it is encoded is still a matter of debate among embryologists.
Self-Organization of Stem Cell Colonies and of Early Mammalian Embryos: Recent Experiments Shed New Light on the Role of Autonomy vs. External Instructions in Basic Body Plan Development. Denker HW Cells 5(4), 39; doi:10.3390/cells5040039

Complex complexityDionisio_{November 28, 2016
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One of the lessons already learned from these studies is a reconciliation of Turing?driven mechanisms and Wolpertian positional information as it is clear that the former drives the emergence of localised signalling sources that, when stabilised, act as references for patterning: positional information is a result of genetically encoded self?assembly. There are more [lessons] to come.
Organoids and the genetically encoded self-assembly of embryonic stem cells David A. Turner, Peter Baillie-Johnson and Alfonso Martinez Arias Bioessays. 38(2): 181–191. doi: 10.1002/bies.201500111

There are more [lessons] to come? Work in progress... stay tuned. Complex complexity.Dionisio_{November 28, 2016
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[...] the interface between genetically encoded self?assembled organoids with designer bioengineering promises much, but the harvesting of this interaction will bring about an interesting reassessment of developmental biology, more focused on molecular mechanisms than on patterns.
Organoids and the genetically encoded self-assembly of embryonic stem cells David A. Turner, Peter Baillie-Johnson and Alfonso Martinez Arias Bioessays. 38(2): 181–191. doi: 10.1002/bies.201500111

interesting reassessment of developmental biology? Will this be in the biology textbooks soon? Complex complexity.Dionisio_{November 28, 2016
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There might be surprises ahead as the molecular mechanisms underlying the generation of organoids might be different from those mediating the corresponding organs in vivo. The organoids in their own way represent a new challenge to the molecular systems that underlie pattern formation and we might find that although the final structures are very similar to those produced in embryos, their paths are different.
Organoids and the genetically encoded self?assembly of embryonic stem cells David A. Turner, Peter Baillie?Johnson and Alfonso Martinez Arias Bioessays. 38(2): 181–191. doi: 10.1002/bies.201500111

There might be surprises ahead? more surprises? a new challenge ? another one? Complex complexity :)Dionisio_{November 28, 2016
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Embryonic development transforms a single celled zygote into a collection of multicellular tissues and organs arranged into structures we call organisms. A key element in this transformation is the ordered generation of cellular diversity which depends on the progressive allocation of cells to specific fates and their self?assembly into three dimensional structures according to emergent rules encoded in those fates. This process depends on programs encoded in, and decoded by, signaling and transcriptional networks.
Organoids and the genetically encoded self?assembly of embryonic stem cells David A. Turner, Peter Baillie?Johnson and Alfonso Martinez Arias Bioessays. 38(2): 181–191. doi: 10.1002/bies.201500111

Complex complexityDionisio_{November 28, 2016
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Understanding the mechanisms of early embryonic patterning and the timely allocation of specific cells to embryonic regions and fates as well as their development into tissues and organs, is a fundamental problem in Developmental Biology. [...] the events underlying the development of these systems are not purely linked to “self?organization,” as often suggested, but rather to a process of genetically encoded self?assembly where genetic programs encode and control the emergence of biological structures.
Organoids and the genetically encoded self?assembly of embryonic stem cells David A. Turner, Peter Baillie?Johnson and Alfonso Martinez Arias Bioessays. 38(2): 181–191. doi: 10.1002/bies.201500111

Complex complexityDionisio_{November 28, 2016
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[...] axons, migrating cells and cells in developmental fields interpret secreted guidance cues and signaling proteins that encode positional information in the form of chemogradient distributions that are stored in the ECM. [...] proteins that have been observed between signal producing and receiving cells are cytoneme-associated and are neither extracellular nor ECM-bound. [...] the cytonemes that mediate Dpp and FGF signaling contact the ECM directly in ways that involve both integrins and specific HSPG interactions.
Cells must express components of the planar cell polarity system and extracellular matrix to support cytonemes Hai Huang and Thomas B Kornberg eLife. 5: e18979. doi: 10.7554/eLife.18979

Complex complexity.Dionisio_{November 24, 2016
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The language of development has a small vocabulary of signaling proteins that consists in part of Fibroblast growth factor (FGF) and Bone morphogenic proteins such as Drosophila Decapentaplegic (Dpp). This language may be used in most or all metazoan organs.
Cells must express components of the planar cell polarity system and extracellular matrix to support cytonemes Hai Huang and Thomas B Kornberg eLife. 5: e18979. doi: 10.7554/eLife.18979

How is that same development language used within different contexts? What controls that?Dionisio_{November 24, 2016
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The embryos of animals develop in a controlled manner that ensures that their tissues and organs form properly and at the right time. These processes depend on molecules called morphogens that are distributed throughout the embryo in specific ways and that are dispersed via extensions that protrude from the surfaces of cells. These extensions, called cytonemes, transport the morphogens across the distances that separate cells and transfer these molecules to target cells via direct contact. [...] the extracellular space is organized and regulated [...] [...] the extracellular matrix is essential for developmental signaling. Future challenges include understanding how the layers of the extracellular matrix form and how information is encoded in these layers for the cytonemes to decipher as they navigate to their targets.
Cells must express components of the planar cell polarity system and extracellular matrix to support cytonemes Hai Huang and Thomas B Kornberg eLife. 5: e18979. doi: 10.7554/eLife.18979

organized and regulated? how? More layers of information? More control levels? How do the cytonemes detect and decipher the encoded information? Complex complexity. :)Dionisio_{November 24, 2016
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[...] an exchange of morphogens alone by diffusion seems highly unlikely. Instead, due to flexibility of mesenchymal cell projections including tunneling nanotubes, it is probable that most of morphogens are transported this path at the right time, punctual site, and dosed amount. Whether microvesicles are involved in the transport of morphogens within the renal stem/progenitor cell niche has to be explored.
Special Morphological Features at the Interface of the Renal Stem/Progenitor Cell Niche Force to Reinvestigate Transport of Morphogens During Nephron Induction Will W. Minuth* and Lucia Denk Biores Open Access. 5(1): 49–60. doi: 10.1089/biores.2015.0039

They were wrong.... again? Oh, well. What else is new? Complex complexity. :)Dionisio_{November 24, 2016
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The transport of morphogens within the renal stem/progenitor cell niche was in the past more simplified described than it really seems to be. Previously it was assumed that mesenchymal and epithelial cells in the renal stem/progenitor cell niche have an intimate contact and that the reciprocal transport of morphogens during induction of a nephron is based exclusively on diffusion. However, recent morphological findings illustrate that mesenchymal and epithelial cell bodies are separated by a striking interface consisting of textural extracellular matrix.
Special Morphological Features at the Interface of the Renal Stem/Progenitor Cell Niche Force to Reinvestigate Transport of Morphogens During Nephron Induction Will W. Minuth* and Lucia Denk Biores Open Access. 5(1): 49–60. doi: 10.1089/biores.2015.0039

Oh, well. What else is new? Complex complexity.Dionisio_{November 24, 2016
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[...] it was presupposed that all morphogens are transported by diffusion. However, earlier and actual literature including present morphological data contradict the general assumption that all involved morphogens are transported by diffusion between mesenchymal and epithelial cells.
Special Morphological Features at the Interface of the Renal Stem/Progenitor Cell Niche Force to Reinvestigate Transport of Morphogens During Nephron Induction Will W. Minuth* and Lucia Denk Biores Open Access. 5(1): 49–60. doi: 10.1089/biores.2015.0039

What did they base that wrong presupposition on? A 7-year-old child would have figured out that diffusion alone would not do the work in many cases. Where is the humility in science? Where are the open-minded researchers? Complex complexity.Dionisio_{November 24, 2016
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Formation of a nephron depends on reciprocal signaling of different morphogens between epithelial and mesenchymal cells within the renal stem/progenitor cell niche. Previously, it has been surmised that a close proximity exists between both involved cell types and that morphogens are transported between them by diffusion. However, actual morphological data illustrate that mesenchymal and epithelial stem/progenitor cell bodies are separated by a striking interface.
Special Morphological Features at the Interface of the Renal Stem/Progenitor Cell Niche Force to Reinvestigate Transport of Morphogens During Nephron Induction Will W. Minuth* and Lucia Denk Biores Open Access. 5(1): 49–60. doi: 10.1089/biores.2015.0039

Complex complexity.Dionisio_{November 24, 2016
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gpuccio @2215: [referring to paper referenced @2214]
Are there really people who believe that two identical twins, if they possessed the same information, would have only one mind? Has human stupidity really got to that point?
The text "it is generally accepted that..." leaves open the possibility that some people may not accept it. The meaning of that part of the text did not hit me until you brought it up. Good catch! Thank you. Sorry, but unfortunately the answer to your questions might be very discouraging, perhaps even scary.Dionisio_{November 23, 2016
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The physico-chemical processes occurring inside cells are under the computational control of genetic (DNA) and epigenetic (internal structural) programming. [...] scant attention has been paid to [...] the molecular biological interpreters that give phenotypic meaning to the sequence information that is quite faithfully replicated during cellular reproduction. The near universality and age of the mapping from nucleotide triplets to amino acids embedded in the functionality of the protein synthetic machinery speaks to the early development of a system of coding which is still extant in every living organism. The early phylogeny of the amino acyl-tRNA synthetase enzymes is discussed in such terms, leading to the conclusion that the observed optimality of the genetic code is a natural outcome of the processes of self-organization that produced it.
The generation of meaningful information in molecular systems Peter R. Wills DOI: 10.1098/rsta.2015.0066 Philosophical Transactions of the Royal Society A: Mathematical, Physical & Engineering Sciences

This paper includes some pseudoscientific statements that may be ignored.Dionisio_{November 23, 2016
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Dioniso: "For example, it is generally accepted that identical twins have distinct minds despite exactly the same blueprints for their construction." Are there really people who believe that two identical twins, if they possessed the same information, would have only one mind? Has human stupidity really got to that point?gpuccio_{November 23, 2016
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Science periodically experiences a discovery of a whole new area of investigation. Two minds identical in terms of the initial design are typically considered to be different if they possess different information. For example, it is generally accepted that identical twins have distinct minds despite exactly the same blueprints for their construction.
The Space of Possible Mind Designs Roman Yampolskiy DOI: 10.1007/978-3-319-21365-1_23 In book: Artificial General Intelligence, pp.218-227

Did anybody say "design"? :)Dionisio_{November 23, 2016
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Importins and exportins influence gene expression by enabling nucleocytoplasmic shuttling of transcription factors. Although importins/exportins are known to regulate spatiotemporal kinetics of NF-?B and other transcription factors governing innate immunity, the mechanistic details of these interactions have not been elucidated and mathematically modelled. Deciphering complex interactions of innate immune responses would thus require specific mechanistic models of regulation of these three transcription factors. By including interactions involving importin-? and exportin we bring the modelling of spatiotemporal kinetics of transcription factors to a more mechanistic level.
Importins promote high-frequency NF-?B oscillations increasing information channel capacity. Korwek Z, Tudelska K, Na??cz-Jawecki P, Czerkies M, Prus W, Markiewicz J, Kocha?czyk M, Lipniacki T Biol Direct. 11(1):61. DOI: 10.1186/s13062-016-0164-z

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Eukaryotic transcription factors in the NF-?B family are central components of an extensive genetic network that activates cellular responses to inflammation and to a host of other external stressors. This network consists of feedback loops that involve the inhibitor I?B?, numerous downstream functional targets, and still more numerous binding sites that do not appear to be directly functional. Under steady stimulation, the regulatory network of NF-?B becomes oscillatory, and temporal patterns of NF-?B pulses appear to govern the patterns of downstream gene expression needed for immune response. Understanding how the information from external stress passes to oscillatory signals and is then ultimately relayed to gene expression is a general issue in systems biology. The regulatory network based on the transcription factor NF-?B has a broad range of influence in eukaryotic cells, which includes orchestrating immune response to inflammation, apoptosis, proliferation, differentiation and many more activities.
Molecular stripping, targets and decoys as modulators of oscillations in the NF-?B/I?B?/DNA genetic network Zhipeng Wang, Davit A. Potoyan, and Peter G. Wolynes J R Soc Interface. 13(122): 20160606. doi: 10.1098/rsif.2016.0606

Complex complexity.Dionisio_{November 20, 2016
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Biological systems use a variety of mechanisms to deal with the uncertain nature of their external and internal environments. Two of the most common motifs employed for this purpose are the incoherent feedforward (IFF) and feedback (FB) topologies. [...] the effectiveness and preference of one motif over the other lies mostly in the practical implementation details and not in their structural properties. [...] the combined circuit has an effective gain that is greater than the sum or product of the gains of the individual components. [...] FB and IFF architectures, though at first glance can appear very different, can be considered as two sides of the same coin. The main differences between the two lie in the ability to adapt to dynamic input fluctuations and the biological constrains in their implementations.
Implementation Considerations, Not Topological Differences, Are the Main Determinants of Noise Suppression Properties in Feedback and Incoherent Feedforward Circuits Gentian Buzi and Mustafa Khammash* Teresa M. Przytycka, Editor PLoS Comput Biol. 12(6): e1004958. doi: 10.1371/journal.pcbi.1004958

Complex complexity. :)Dionisio_{November 20, 2016
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