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DNA’s scissors’ lock mechanism

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From Phys.org:

Alyssa Ward, a graduate student in Desiderio’s laboratory, says that the system works like the bolt on a door. The PHD piece is the lock, H3K4me3 is the key and the deleted piece is the actual bolt. When all of the pieces are normal, H3K4me3 unlocks the PHD segment, which moves the bolt so that the door can open— i.e., so that RAG can cut. If there is a mutation in the PHD, the key won’t fit the lock, so the door remains bolted. But, if the lock or bolt is removed entirely, the door can open and close freely.

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Hat tip: Timothy Kershner

Comments
Well, in a very humble way, that’s what I have been trying to do here in the last few years. For what I can. And I will go on.
Gpuccio, I am curious. How are you actually going this-- humble or not?hrun0815
January 1, 2015
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#82 DATCG Thank you for posting that interesting information. Happy New Year!Dionisio
January 1, 2015
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#40 gpuccio
The main reasons for my conviction of the important role of transposons as ID tools are the following: a) ID can be inferred when functional results are achieved which are well beyond the scope of any non design explanation (this is the basic point in ID theory, so I will not deal with it in detail here). b) Transposons are increasingly implied in important remodeling of the genome which, in the course of evolution, generates new important functional configurations, which are well beyond the scope of any non design explanation. c) Therefore, it is perfectly natural to hypothesize that the working of transposons, when it generates new complex functional configurations, is guided, and not random. IOWs, I hypothesize, at least in many cases, ID through guided transposon activity, rather than through guided mutations. Is the “mechanism” observable? In a sense, it is. The best scenario for biological ID is an intervention of the designer’s consciousness in biological events through a consciousness-matter interface at quantum level. That is not so strange, because it is exactly what has been hypothesized as an explanation of the consciousness-matter interface in the human brain (see, for example, Eccles). Now, while in the future we could be able to detect those quantum interface directly, for the moment we can observe its results: the input of functional information into material events which could never generate that information. That is the essence of ID theory, and it is observable.
I think the above quoted insightful compacted explanation, that you wrote at the end of last year, should be repeated at the beginning of this year. :) Here's my first dumb question to start the new year: regarding this note "(see, for example, Eccles)", what is Eccles? Thank you.Dionisio
January 1, 2015
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gpuccio: The whole point is that complex functional information can be exactly defined, and that it is the result of design. As we said, planetary orbits are functionally complex. They make the days and seasons and longer periods associated with the rise and fall of civilizations. It took the very highest levels of human ingenuity and craftsmanship to make a tiny simulacrum of the heavens.Zachriel
December 31, 2014
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Zachriel: The whole point is that complex functional information can be exactly defined, and that it is the result of design.gpuccio
December 31, 2014
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Looking for and applying design principles is a great educational and research heuristic going forward as seen in above links for applying systems engineering concepts, even if old guard Darwinist faithful refuse to acknowledge the ascendance of the Design Paradigm. Towards the rational design of synthetic cells with prescribed population dynamics Not only is it rational to use design terms, it is necessary among scientist, programmers and engineers developing new methods of research, treatments and solutions, including the "rational design of synthetic cells with prescribed population dynamics." Why is a "programming language" or "engineering" utilized to produce new living cells? Because, treating cellular and biological functions as modular, programmable objects and systems architecture works. Genetic Engineering of Living Cells In developing programs and visual tools with languages like GEC, design terms are not denigrated, but elevated as central to solving problems. A spin-off of Design-centric paradigm.... Functional Biological Parts Registry It is a misleading to state design terms are limited to descriptions for lay people or those uninformed about complex biological processes. That is but one use of design terms. As seen by scientific research, design terms and methodologies are at the forefront utilized by academics, programmers and engineers to collaborate and forward the understanding of life.DATCG
December 31, 2014
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"Design terms" are not merely for lay people, but utilized by scientist and engineers alike for the great purpose and communication of complex ideas in systems biology. One need not look far today as "design terms" and design processes are routinely discussed at highest levels of academics and applied sciences in surgery, biology, regenerative medicine and biomedical engeineering. Why? Because it makes perfect sense to do so. Hardly an "IDer" conspiracy, but a common sense approach to real life application in science...
A systems engineering perspective on homeostasis and disease Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA 2Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA 3Department of Surgery, The University of Chicago, Chicago, IL, USA 4Department of Biomedical Engineering, Rutgers University, Piscataway, NJ, USA 5Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ, USA 6Department of Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA
... there is much to be learned about biological complexity from engineered systems. That sentence is followed by the obligatory denial...
This is not to say that biological systems are engineered systems: biological systems are clearly distinct and different by virtue of having resulting from evolution as opposed to design.
What great fear the unguided live in.DATCG
December 31, 2014
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gpuccio: As you should know, planetary orbits are not functionally complex in the ID sense: they are the result of laws. For those unaware of the underlying symmetries involved, it was extremely complex. That's the whole point, of course.Zachriel
December 31, 2014
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Zachriel: As you should know, planetary orbits are not functionally complex in the ID sense: they are the result of laws. And the causal link bewtween consciousness, design and functional complexity is an inference well established by empirically observed facts.gpuccio
December 31, 2014
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Hematopoietic stem cell dysfunction underlies the progressive lymphocytopenia in XLF/Cernunnos deficiency DOI: http://dx.doi.org/10.1182/blood-2014-05-574863 http://www.bloodjournal.org/content/124/10/1622.abstract?sso-checked=trueDionisio
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Quantitation of DNA double-strand break resection intermediates in human cells doi: 10.1093/nar/gkt1309 http://nar.oxfordjournals.org/content/42/3/e19.abstractDionisio
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Small-Molecule DNA Methylation Inhibitor doi: 10.1158/1078-0432.CCR-14-1553 http://clincancerres.aacrjournals.org/content/20/24/6504.abstractDionisio
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Unraveling the Complexities of DNA-Dependent Protein Kinase Autophosphorylation doi: 10.1128/MCB.01554-13 http://mcb.asm.org/content/34/12/2162.abstractDionisio
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DNA-dependent Protein Kinase Regulates DNA End Resection in Concert with Mre11-Rad50-Nbs1 (MRN) and Ataxia Telangiectasia-mutated (ATM)* doi: 10.1074/jbc.M113.514398 The resection of DNA double strand breaks initiates homologous recombination (HR) and is critical for genomic stability. http://www.jbc.org/content/288/52/37112.abstractDionisio
December 31, 2014
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KAP-1 Promotes Resection of Broken DNA Ends Not Protected by ?-H2AX and 53BP1 in G1-Phase Lymphocytes doi: 10.1128/MCB.00441-14 http://mcb.asm.org/content/34/15/2811.abstractDionisio
December 31, 2014
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gpuccio: It’s functionally complex. We don’t know any non design explanation for functionally complex things. But we know well that conscious, intelligent, purposeful beings can generate those kind of things. Therefore, we have a definite “link of causation” to infer design for biological objects, and that is in no way “a gap argument”. The planetary orbits are functionally complex. They keep track of time and seasons and the rise and fall of empires. We don't know any non-design explanation for something so functionally complex. But we know that we can create functionally complex mechanisms with elaborate gears and wheels and pinions that emulate the planetary movements. While this is *not* a link of causation (where did you get that idea?), we infer the designer of planetary orbits is obviously someone with far more design capabilities than the meager efforts of the crafters and scholars who make the pale imitation mechanisms.Zachriel
December 31, 2014
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Aurelio quoting Box as alleged evidence ID is not science:
“How the designer operates is beyond the scope of science…”
ID is about the DESIGN. Why do our opponents think their willful ignorance means something? How the designers of Stonehenge operated is beyond science. Does that mean archaeology isn't science?Joe
December 31, 2014
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Aurelio Smith:
Giving it testable entailments might be the first step on the road to making “Intelligent Design” into some sort of scientific endeavor.
And that is a road your position will never step foot on. :razz:Joe
December 31, 2014
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An Overview of the Intrathymic Intricacies of T Cell Development doi: 10.4049/?jimmunol.1302259 The generation of a functional and diverse repertoire of T cells occurs in the thymus from precursors arriving from the bone marrow. In this article, we introduce the various stages of mouse thymocyte development and highlight recent work using various in vivo, and, where appropriate, in vitro models of T cell development that led to discoveries in the regulation afforded by transcription factors and receptor–ligand signaling pathways in specifying, maintaining, and promoting the T cell lineage and the production of T cells. This review also discusses the role of the thymic microenvironment in providing a niche for the successful development of T cells. In particular, we focus on advances in Notch signaling and developments in Notch ligand interactions in this process. http://www.jimmunol.org/content/192/9/4017.abstractDionisio
December 31, 2014
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Upright BiPed @ 66: Thank you very much. That indeed looks like the argument I wanted. After I've studied it, I'll likely post a question or two on that thread. Belated Merry Christmas and Happy New Year, to you and to all.Charles
December 31, 2014
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A Critical Role for the Regulated Wnt–Myc Pathway in Naive T Cell Survival doi: 10.4049/?jimmunol.1401238 Wnt signaling is involved in T cell development, activation, and differentiation. However, the role for Wnt signaling in mature naive T cells has not been investigated. http://www.jimmunol.org/content/194/1/158.abstractDionisio
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Hello Charles, Happy New Year. I hope this exchange might help explain it. If you have questions, I am happy to respond.Upright BiPed
December 31, 2014
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Hello GP! Happy New Year to you my dear friend!Upright BiPed
December 31, 2014
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10 years ago... New concepts in the regulation of an ancient reaction: transposition by RAG1/RAG2. A major challenge has been to determine how the transposition activity of the RAG proteins is regulated in vivo. Although a variety of mechanisms have been suggested by recent studies, a clear resolution of this issue remains elusive. http://www.ncbi.nlm.nih.gov/pubmed/15242411 But today we finally know how the transposition activity of the RAG proteins is regulated in vivo. :)Dionisio
December 31, 2014
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Off topic: If you have used EndNote for organizing research papers online, you may want to try Zotero. A friend from Canada recommended it to me. It works very well. I use it in combination with Mind Meister and a set of private WordPress web logs. I plan to share the main link with y'all when I get it well cooked (no salt added). :) Happy New Year to all! (including the interlocutors that don't like my dumb questions). :)Dionisio
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Fc Receptors for Immunoglobulins and Their Appearance during Vertebrate Evolution doi: 10.1371/journal.pone.0096903 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4016189/ http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0096903
Receptors interacting with the constant domain of immunoglobulins (Igs) have a number of important functions in vertebrates. They facilitate phagocytosis by opsonization, are key components in antibody-dependent cellular cytotoxicity as well as activating cells to release granules. These molecules are not found in cartilagous fish and may first appear within bony fishes, indicating a major step in Fc receptor evolution at the appearance of bony fish. In contrast, the receptor for IgA is only found in placental mammals, indicating a relatively late appearance. The IgM and IgA/M receptors are first observed in the monotremes, exemplified by the platypus, indicating an appearance during early mammalian evolution. Clearly identifiable classical receptors for IgG and IgE are found only in marsupials and placental mammals, but closely related receptors are found in the platypus, indicating a second major step in Fc receptor evolution during early mammalian evolution, involving the appearance of classical IgG and IgE receptors from FcRL molecules and IgM and IgA/M receptors from PIGR.
https://www.youtube.com/embed/8dnUs2AqWvs :)Dionisio
December 31, 2014
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Upright BiPed: Happy New Year to you, from my heart! :)gpuccio
December 31, 2014
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Aurelio Smith: I hope your hat is good to digest! :) "Giving it testable entailments might be the first step on the road to making “Intelligent Design” into some sort of scientific endeavor. I wish you the best of luck if you decide to instigate or cooperate on such an exercise, sincerely." Well, in a very humble way, that's what I have been trying to do here in the last few years. For what I can. And I will go on. Happy New Year! :)gpuccio
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Upright BiPed @ 51: This is off topic, but, a couple times recently you mentioned in your other posts on other threads that regarding the DNA/RNA transcription apparatus, the logical separation of the code from the physical mechanism was an essential separation (or words to that effect, hopefully I've not so mangled your point that you realize to what I'm referring). I've wanted to understand that 'separation is essential' argument in greater detail, but I wasn't around whenever/wherever you did, so could you kindly post a link to your most detailed explanation... please? Thank you for your assistance and patience.Charles
December 31, 2014
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Dionisio: Happy New Year, my friend! :)gpuccio
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