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Mystery at the heart of life

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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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Comments
There are numerous problems with the morphogen gradient model. Many doubts about the functioning or existence of these so-called “morphogen” gradients have been raised, with alternatives and elaborations, and transport mechanisms other than diffusion being proposed. The force driving this alternating pattern has not yet been documented [...] The precise cytoskeletal signal remains to be found [...] We now have another explanation for so-called “morphogen” gradients. This gradient is merely a temporary epiphenomenon, a byproduct of differentiation wave activity. It is plausible that there are differences between early versus late developmental cell state splitter signal events.
The organelle of differentiation in embryos: the cell state splitter Natalie K. Gordon and Richard Gordon Theor Biol Med Model. 2016; 13: 11. doi: 10.1186/s12976-016-0037-2
Dionisio
September 19, 2016
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That all of these interactions between genetically identical cells should somehow work themselves out in the creation of many distinct microenvironments, all in the right place at the right time, is about as plausible as having a musically untrained crowd of chattering people suddenly switch their cacophony to four part harmony and perform Mozart’s complete Ave Verum Corpus.
The organelle of differentiation in embryos: the cell state splitter Natalie K. Gordon and Richard Gordon Theor Biol Med Model. 2016; 13: 11. doi: 10.1186/s12976-016-0037-2
Beautifully said! A very clear description of the given scenario.Dionisio
September 18, 2016
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Multicellular organisms are made of 4D spatiotemporal arrays of different cell types. The identity and function of any individual cell is defined and presumably determined by the specific complement of proteins and RNA that the cell contains. Proteins and RNA are encoded in the genome. While each cell has a complete copy of the whole genome, each cell uses only a portion of the total gene products encoded in it. The mechanism by which this process of differentiation of the one-cell embryo (i.e., the fertilized egg) into more than 3.72×1013 cells of up to 7000 cell types is accomplished over space and time is the central puzzle of embryology.
The organelle of differentiation in embryos: the cell state splitter Natalie K. Gordon and Richard Gordon Theor Biol Med Model. 2016; 13: 11. doi: 10.1186/s12976-016-0037-2
Dionisio
September 18, 2016
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During differentiation, EBs contain a temporally-shifting mixture of various cell lineages, each with its own gene expression profile, signaling characteristics, and lineage history. Additional experiments with combinations of Wnt3 and CHIR are needed to further validate the route of regulation. Adding selective fluorescence markers for earlier or later stages of differentiation and single-cell mRNA analysis can extend the spatio-temporal depiction of expression trend and improve the clock accuracy, providing a better insight into whole EB inter-related processes.
Integrated live imaging and molecular profiling of embryoid bodies reveals a synchronized progression of early differentiation Jonathan Boxman,1,* Naor Sagy,1,* Sirisha Achanta,2 Rajanikanth Vadigepalli,a,2 and Iftach Nachman Sci Rep. 2016; 6: 31623. doi: 10.1038/srep31623
Dionisio
September 18, 2016
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The coordinated progression of different cell lineages is essential for the formation of functional tissues and organs. Embryonic stem cells can be aggregated into embryoid bodies (EBs), which have the potential to differentiate to a diverse population of adult specialized cells. The differentiation of EBs into cells of the three germ layers, even in the absence of externally added directive signals, indicates that the required signals for these processes can autonomously build up within each EB. How these signals interact to coordinate the growth and relative composition of multiple lineages is not fully characterized.
Integrated live imaging and molecular profiling of embryoid bodies reveals a synchronized progression of early differentiation Jonathan Boxman,1,* Naor Sagy,1,* Sirisha Achanta,2 Rajanikanth Vadigepalli,a,2 and Iftach Nachman Sci Rep. 2016; 6: 31623. doi: 10.1038/srep31623
Dionisio
September 18, 2016
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Embryonic stem cells can spontaneously differentiate into cell types of all germ layers within embryoid bodies (EBs) in a highly variable manner. Whether there exists an intrinsic differentiation program common to all EBs is unknown.
Integrated live imaging and molecular profiling of embryoid bodies reveals a synchronized progression of early differentiation Jonathan Boxman,1,* Naor Sagy,1,* Sirisha Achanta,2 Rajanikanth Vadigepalli,a,2 and Iftach Nachman Sci Rep. 2016; 6: 31623. doi: 10.1038/srep31623
Dionisio
September 18, 2016
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The red-green system samples the visual world at a lower resolution than the achromatic system. [...] the nervous system represents these two pieces of information with separate pathways that emerge as early as the photoreceptor synapse: one chiefly concerned with high-resolution achromatic vision and a second, lower-resolution color system.
The elementary representation of spatial and color vision in the human retina Ramkumar Sabesan1,*,†,‡, Brian P. Schmidt2,†, William S. Tuten1 and Austin Roorda1 Science Advances Vol. 2, no. 9, e1600797 DOI: 10.1126/sciadv.1600797
Dionisio
September 18, 2016
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A single photoreceptor is sensitive to both the intensity and the wavelength of light falling on it and, therefore, confounds brightness and color signals. Our visual system ultimately constructs a representation of the external world from the output of the photoreceptor mosaic in which color and achromatic contrast are divorced. How, and which, postreceptoral neural pathways recover and segregate this multiplexed information from individual receptors remains unresolved.
The elementary representation of spatial and color vision in the human retina Ramkumar Sabesan1,*,†,‡, Brian P. Schmidt2,†, William S. Tuten1 and Austin Roorda1 Science Advances Vol. 2, no. 9, e1600797 DOI: 10.1126/sciadv.1600797
Dionisio
September 18, 2016
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The retina is the most accessible element of the central nervous system for linking behavior to the activity of isolated neurons. [...] the nervous system encodes high-resolution achromatic information and lower-resolution color signals in separate pathways that emerge as early as the first synapse.
The elementary representation of spatial and color vision in the human retina Ramkumar Sabesan1,*,†,‡, Brian P. Schmidt2,†, William S. Tuten1 and Austin Roorda1 Science Advances Vol. 2, no. 9, e1600797 DOI: 10.1126/sciadv.1600797
Dionisio
September 17, 2016
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[...] diffusion, extracellular interactions i.e., Nodal-receptor binding, Nodal-Lefty inhibitor binding, and selective ligand destruction collectively shape and refine the Nodal morphogen gradient.
Extracellular interactions and ligand degradation shape the nodal morphogen gradient Yin Wang,1,2,† Xi Wang,3,† Thorsten Wohland,2,3,* and Karuna Sampath eLife. 2016; 5: e13879. doi: 10.7554/eLife.13879
Dionisio
September 15, 2016
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The correct distribution and activity of secreted signaling proteins called morphogens is required for many developmental processes. Nodal morphogens play critical roles in embryonic axis formation in many organisms. Models proposed to generate the Nodal gradient include diffusivity, ligand processing, and a temporal activation window. But how the Nodal morphogen gradient forms in vivo remains unclear.
Extracellular interactions and ligand degradation shape the nodal morphogen gradient Yin Wang,1,2,† Xi Wang,3,† Thorsten Wohland,2,3,* and Karuna Sampath eLife. 2016; 5: e13879. doi: 10.7554/eLife.13879
Professor L.M. of the U. of T. in Canada claimed to know exactly how morphogen gradients form. The authors of this paper should consult with professor L.M.Dionisio
September 15, 2016
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"The complexity builds in robustness. Robustness is important in enabling organisms to resist unfavorable changes in their environments or genomes." Denis Noble http://www.thebestschools.org/dialogues/evolution-denis-noble-interview/Dionisio
September 13, 2016
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At first, it was just a premonitory tremor: the piecing together of a rudimentary whole human genome in 2001. Then, just two years later, came an earth-shaking eruption: the completion of the Human Genome Project. This explosive event rocked the molecular genetics landscape and released bioscientific forces that to this day show no signs of abating. Ceaseless flows of academic brainstorming and commercial innovation are reshaping old fields and creating new ones, ultimately spreading fertility to downstream disciplines such as epigenetics and epigenomics.
GEN News Awaken Dormant DNA, Epigenetically Epigenetics Isn’t Limited to Studying Marks on Chromatin Rob Ranulph Jones http://www.genengnews.com/gen-articles/awaken-dormant-dna-epigenetically/5818/
Dionisio
September 10, 2016
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Circulating Biomarkers: A Complex Space with Multiple Parts The topic of circulating biomarkers includes markers as simple as glucose or cholesterol as well as protein biomarkers such as C-reactive protein (CRP), circulating cell-free DNA (cfDNA), or circulating RNA. In newer cases, it also includes genes such as BCRA1, KRAS, and others. Recently, the field has expanded to include circulating tumor cells (CTCs) and exosomes or extracellular vesicles (EVs).
Trends in Various Segments of the Circulating Biomarkers Space Circulating Biomarkers: A Complex Space with Multiple Parts Gary Oosta, Ph.D., Enal Razvi, Ph.D. http://www.genengnews.com/insight-and-intelligence/trends-in-various-segments-of-the-circulating-biomarkers-space/77900736/
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September 10, 2016
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When cells get together, they have a curious way of breaking bread. They take bites out of each other, by means of a process called bidirectional trans-endocytosis. Then they go their separate ways, moving as needed to form or repair the body’s tissues. Although cells have long been known to tear themselves away from each other, the etiquette of the process has been unclear. What codes of behavior do cells observe when they regulate contact-mediated repulsion?
GEN News Cells Take Call, Then Eat and Run http://www.genengnews.com/gen-news-highlights/cells-take-call-then-eat-and-run/81253179/
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September 10, 2016
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Researchers at MIT say they have deciphered the structure of one type of long noncoding RNA (lncRNA) and used that information to figure out how it interacts with a cellular protein to control the development of heart muscle cells. This is one of first studies to link the structure of lncRNAs to their function. "Emerging data points to fundamental roles for many of these molecules in development and disease, so we believe that determining the structure of lncRNAs is critical for understanding how they function," says Laurie Boyer, Ph.D. Learning more about how lncRNAs control cell differentiation could offer a new approach to developing drugs for patients whose hearts have been damaged by cardiovascular disease, aging, or cancer.
GEN News MIT Team Shows How lncRNA Works http://www.genengnews.com/gen-news-highlights/mit-team-shows-how-lncrna-works/81253184/
Dionisio
September 10, 2016
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@1978-1983: This Fgfr2 seems like a very 'sexy' protein, doesn't it? :)Dionisio
September 10, 2016
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The endodermal and ectodermal domains of Fgfr2 play distinct roles in urethral tubulogenesis; however, in both tissue compartments Fgfr2 controls epithelial cell proliferation, stratification and adhesion. Coordination of these cellular processes in the urethral epithelium and the overlying surface ectoderm is required both for synchronous development and for structural integrity of the developing urethral tube and prepuce.
Tissue-specific roles of Fgfr2 in development of the external genitalia Marissa L. Gredler,1 Ashley W. Seifert,1,* and Martin J. Cohn Development. 142(12): 2203–2212. doi: 10.1242/dev.119891
Complex complexity.Dionisio
September 10, 2016
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Together, these data raise the intriguing possibility that Fgfr2 in the genital tubercle epithelia drives epithelial maturation by coupling proliferation with cellular morphogenesis. An important but poorly understood feature of sexually dimorphic external genital development is internalization of the male urethra [...] [...] urethral tubulogenesis and internalization are interdependent processes that each require Fgfr2.
Tissue-specific roles of Fgfr2 in development of the external genitalia Marissa L. Gredler,1 Ashley W. Seifert,1,* and Martin J. Cohn Development. 142(12): 2203–2212. doi: 10.1242/dev.119891
Complex complexity.Dionisio
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[...] the cells are able to sense increases in mechanical force [...] [...] normal ventrolateral preputial development requires strong epithelial integrity at the ectodermal-endodermal boundary. [...] this axis along the ventral midline of the genital tubercle acts as a scaffold around which the preputial swellings eventually fuse. Coordinated cell shape changes mediate tubulogenesis of many organs [...] Cytoskeletal reorganizations underlie cell shape changes, require cell adhesion and occur in a cell-cycle-dependent manner [...]
Tissue-specific roles of Fgfr2 in development of the external genitalia Marissa L. Gredler,1 Ashley W. Seifert,1,* and Martin J. Cohn Development. 142(12): 2203–2212. doi: 10.1242/dev.119891
Complex complexity.Dionisio
September 10, 2016
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In both the urethral and the surface epithelia of the genital tubercle, Fgfr2 promotes proliferation by mediating the G1/S cell cycle transition and is required for adhesion and morphological maturation of basal epithelial cells. [...] structural integrity of the ectodermal-endodermal boundary at the ventral midline integrates these morphogenetic events and is regulated by Fgf signaling. Fgfr2 mediates the same cellular processes in both the endoderm and the ectoderm of the developing genital tubercle.
Tissue-specific roles of Fgfr2 in development of the external genitalia Marissa L. Gredler,1 Ashley W. Seifert,1,* and Martin J. Cohn Development. 142(12): 2203–2212. doi: 10.1242/dev.119891
Complex complexity.Dionisio
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[...] Fgfr2 acts as a link between hormonal and genetic regulation of external genital development. [...] urethral tubulogenesis, prepuce morphogenesis, and sexually dimorphic patterning of the urethra are three crucial processes in external genital development that are controlled by independent regions of Fgfr2 activity. [...] Fgfr2 activity in the endoderm mediates urethral epithelial maturation, whereas ectodermal Fgfr2 is required for formation of the prepuce.
Tissue-specific roles of Fgfr2 in development of the external genitalia Marissa L. Gredler,1 Ashley W. Seifert,1,* and Martin J. Cohn Development. 142(12): 2203–2212. doi: 10.1242/dev.119891
Dionisio
September 10, 2016
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Tubular morphogenesis (tubulogenesis) is essential for normal embryonic development [...] A variety of mechanisms can drive tube formation, such as the wrapping mechanism of neurulation, budding of the salivary and mammary glands, and the delamination/migration process of bile duct development [...] External genital development involves a series of budding and fusion events. [...] urethral tubulogenesis involves multiple morphogenetic processes, including evagination of the cloacal wall to form the bilaminar plate, epithelial stratification and maturation, and remodeling of the plate to form the lumen of the tube.
Tissue-specific roles of Fgfr2 in development of the external genitalia Marissa L. Gredler,1 Ashley W. Seifert,1,* and Martin J. Cohn Development. 142(12): 2203–2212. doi: 10.1242/dev.119891
Dionisio
September 10, 2016
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[...] discovering the identity of the deubiquitylase that removes H3 ubiquitylation may provide key insight into the dynamics of DNA methylation regulation at the level of histone ubiquitylation. [...] direct evidence of USP7 catalyzed deubiquitylation of H3 is lacking. We speculate that epigenetic mechanisms of multivalency and allostery are more widespread and add additional layers of complexity, specificity, and connectivity to chromatin recognition, modification patterning, and genome regulation.
Hemi-methylated DNA regulates DNA methylation inheritance through allosteric activation of H3 ubiquitylation by UHRF1. Harrison JS1,2, Cornett EM3, Goldfarb D4, DaRosa PA5, Li ZM6, Yan F7, Dickson BM3, Guo AH1, Cantu DV1, Kaustov L8, Brown PJ8, Arrowsmith CH8, Erie DA9, Major MB4,7, Klevit RE5, Krajewski K1, Kuhlman B1,2, Strahl BD1,2, Rothbart SB3. DOI: http://dx.doi.org/10.7554/eLife.17101 eLife 2016;5:e17101
This is not any god-of-the-gaps. This is just complex complexity. :) Unending revelation of the ultimate reality.Dionisio
September 8, 2016
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[...] it is intriguing to speculate that UHRF1 functions to provide a nucleation event for DNMT1 recruitment to chromatin. Future studies mapping the genome-wide distribution of UHRF1-directed H3 ubiquitylation in relation to DNA methylation patterning will clarify the relationship between UHRF1 and DNMT1 activities. How might HeDNA binding alter the substrate preference of UHRF1 directed ubiquitylation? Determining the active conformation of UHRF1 will be an important step in further understanding the regulation imparted by HeDNA.
Hemi-methylated DNA regulates DNA methylation inheritance through allosteric activation of H3 ubiquitylation by UHRF1. Harrison JS1,2, Cornett EM3, Goldfarb D4, DaRosa PA5, Li ZM6, Yan F7, Dickson BM3, Guo AH1, Cantu DV1, Kaustov L8, Brown PJ8, Arrowsmith CH8, Erie DA9, Major MB4,7, Klevit RE5, Krajewski K1, Kuhlman B1,2, Strahl BD1,2, Rothbart SB3. DOI: http://dx.doi.org/10.7554/eLife.17101 eLife 2016;5:e17101
This is not any god-of-the-gaps. This is just complex complexity. :) Unending revelation of the ultimate reality.Dionisio
September 8, 2016
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[...] it remains to be seen whether uncoupling UHRF1 from HeDNA recognition changes its residence genome-wide [...] coordinated recognition of H3 and DNA, independent of HeDNA discrimination, drives chromatin interaction. Further studies are necessary to examine the biological consequence of different patterns of H3 ubiquitylation by UHRF1 and their relationship to pre-existing histone PTM signatures.
Hemi-methylated DNA regulates DNA methylation inheritance through allosteric activation of H3 ubiquitylation by UHRF1. Harrison JS1,2, Cornett EM3, Goldfarb D4, DaRosa PA5, Li ZM6, Yan F7, Dickson BM3, Guo AH1, Cantu DV1, Kaustov L8, Brown PJ8, Arrowsmith CH8, Erie DA9, Major MB4,7, Klevit RE5, Krajewski K1, Kuhlman B1,2, Strahl BD1,2, Rothbart SB3. DOI: http://dx.doi.org/10.7554/eLife.17101 eLife 2016;5:e17101
This is not any god-of-the-gaps. This is just complex complexity. :) Unending revelation of the ultimate reality.Dionisio
September 8, 2016
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The epigenetic inheritance of DNA methylation requires UHRF1, a histone- and DNA-binding RING E3 ubiquitin ligase that recruits DNMT1 to sites of newly replicated DNA through ubiquitylation of histone H3. UHRF1 binds DNA with selectivity towards hemi-methylated CpGs (HeDNA); however, the contribution of HeDNA sensing to UHRF1 function remains elusive.
Hemi-methylated DNA regulates DNA methylation inheritance through allosteric activation of H3 ubiquitylation by UHRF1 Joseph S Harrison, Evan M Cornett, Dennis Goldfarb, Paul A DaRosa, Zimeng M Li, Feng Yan, Bradley M Dickson, Angela H Guo, Daniel V Cantu, Lilia Kaustov, Peter J Brown, Cheryl H Arrowsmith, Dorothy A Erie, Michael B Major, Rachel E Klevit, Krzysztof Krajewski, Brian Kuhlman, Brian D Strahl, Scott B Rothbart DOI: http://dx.doi.org/10.7554/eLife.17101 eLife 2016;5:e17101
Dionisio
September 8, 2016
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MBD2 is an integral part of the NuRD complex with many unanswered questions regarding its molecular and biological functions. In order to address these questions, it is essential to unravel the complexities of different isoforms of MBD2 in association with NuRD. Future investigations into MBD2 functions may have important implications for the study of pluripotency, immunity, and cancer, in addition to revealing insights into broader epigenetic mechanisms.
Emerging Molecular and Biological Functions of MBD2, a Reader of DNA Methylation Kathleen H. Wood and Zhaolan Zhou Front Genet. 7: 93. doi: 10.3389/fgene.2016.00093
This is not god-of-the-gaps. This is just complex complexity. :) Unending revelation of the ultimate reality.Dionisio
September 8, 2016
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One study determined that most NuRD complexes in mammalian cells contain MBD3 rather than MBD2 (Zhang et al., 1999), but the dynamics of these interactions in vivo have not been fully determined. Additional biochemical evidence is necessary to determine if misregulation of NuRD activity occurs upon loss of MBD2 in the brain. The different isoforms of MBD2 introduce further complications into models of MBD2/NuRD function.
Emerging Molecular and Biological Functions of MBD2, a Reader of DNA Methylation Kathleen H. Wood and Zhaolan Zhou Front Genet. 7: 93. doi: 10.3389/fgene.2016.00093
This is not god-of-the-gaps. This is just complex complexity. :) Unending revelation of the ultimate reality.Dionisio
September 8, 2016
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There are also many unanswered questions regarding the in vivo dynamics of the NuRD complex and MBD2 or MBD3. The spatiotemporal expression patterns of MBD2 and MBD3 raise further questions about NuRD formation and function, particularly in adult tissues where MBD3 is nearly undetectable but MBD2 is highly expressed [...] it remains to be determined why loss of MBD3, even conditionally in specific tissues, has severe phenotypic consequences, while constitutive loss of MBD2 has only mild effects [...]
Emerging Molecular and Biological Functions of MBD2, a Reader of DNA Methylation Kathleen H. Wood and Zhaolan Zhou Front Genet. 7: 93. doi: 10.3389/fgene.2016.00093
Dionisio
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