<div dir="ltr">Sung -- regarding:<div><br></div><div><span style="color:rgb(0,0,0);font-family:Calibri,Helvetica,sans-serif,Helvetica,EmojiFont,'Apple Color Emoji','Segoe UI Emoji',NotoColorEmoji,'Segoe UI Symbol','Android Emoji',EmojiSymbols;font-size:16px">The reason epigenetics (defined here as the process of inheritance without imlplicating any changes in the nucleotide sequences of DNA) was not mentioned in my previous post is because I was mainly interested in the bottom-up (from micro to macro) mechanism of genetics, not the top-down (from macro to micro) mechanism. It is interesting to note that our brain seems unable to handle both bottom-up and top-down mechanisms simultaneously, perhaps it may have something to do with the fact that we have two brain hemispheres (Yin and Yang) but only one vocal cord (the Dao). </span><br></div><div><span style="color:rgb(0,0,0);font-family:Calibri,Helvetica,sans-serif,Helvetica,EmojiFont,'Apple Color Emoji','Segoe UI Emoji',NotoColorEmoji,'Segoe UI Symbol','Android Emoji',EmojiSymbols;font-size:16px"><br></span></div><div><span style="color:rgb(0,0,0);font-family:Calibri,Helvetica,sans-serif,Helvetica,EmojiFont,'Apple Color Emoji','Segoe UI Emoji',NotoColorEmoji,'Segoe UI Symbol','Android Emoji',EmojiSymbols">It is interesting that I early realized the difficulty many folks have with visualizing at one time both the top-down AND bottom-up aspects of the compositional hierarchy:</span></div><div><span style="color:rgb(0,0,0);font-family:Calibri,Helvetica,sans-serif,Helvetica,EmojiFont,'Apple Color Emoji','Segoe UI Emoji',NotoColorEmoji,'Segoe UI Symbol','Android Emoji',EmojiSymbols"> [large scale constraints -> [activity in focus <- [small scale affordances]]]</span></div><div><span style="color:rgb(0,0,0);font-family:Calibri,Helvetica,sans-serif,Helvetica,EmojiFont,'Apple Color Emoji','Segoe UI Emoji',NotoColorEmoji,'Segoe UI Symbol','Android Emoji',EmojiSymbols"><br></span></div><div><span style="color:rgb(0,0,0);font-family:Calibri,Helvetica,sans-serif,Helvetica,EmojiFont,'Apple Color Emoji','Segoe UI Emoji',NotoColorEmoji,'Segoe UI Symbol','Android Emoji',EmojiSymbols">Perhaps your suggestion is involved here as well!</span></div><div><span style="color:rgb(0,0,0);font-family:Calibri,Helvetica,sans-serif,Helvetica,EmojiFont,'Apple Color Emoji','Segoe UI Emoji',NotoColorEmoji,'Segoe UI Symbol','Android Emoji',EmojiSymbols"><br></span></div><div><span style="color:rgb(0,0,0);font-family:Calibri,Helvetica,sans-serif,Helvetica,EmojiFont,'Apple Color Emoji','Segoe UI Emoji',NotoColorEmoji,'Segoe UI Symbol','Android Emoji',EmojiSymbols">STAN </span></div></div><div class="gmail_extra"><br><div class="gmail_quote">On Sat, Apr 28, 2018 at 5:17 PM, Sungchul Ji <span dir="ltr"><<a href="mailto:sji@pharmacy.rutgers.edu" target="_blank">sji@pharmacy.rutgers.edu</a>></span> wrote:<br><blockquote class="gmail_quote" style="margin:0 0 0 .8ex;border-left:1px #ccc solid;padding-left:1ex">
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<p style="margin-top:0;margin-bottom:0"><span style="font-size:12pt">Hi Arthur and FISers,</span><br>
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Thank you for asking an important question. The reason epigenetics (defined here as the process of inheritance without imlplicating any changes in the nucleotide sequences of DNA) was not mentioned in my previous post is because I was mainly interested in
the bottom-up (from micro to macro) mechanism of genetics, not the top-down (from macro to micro) mechanism. It is interesting to note that our brain seems unable to handle both bottom-up and top-down mechanisms simultaneously, perhaps it may have something
to do with the fact that we have two brain hemispheres (Yin and Yang) but only one vocal cord (the Dao). </div>
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One way to integrate the bottom-up and top-down mechanisms underlying genetic phenomenon may be to invoke the principle of vibrational resonance -- to view both the micro-scale DNA and the macro-scale environment of organisms as vibrational systems or systems
of oscillators that can exchange information and energy through the well-known mechanisms of resonance (e.g., the resonance between the oscillatory motions of the swing and the arms of the mother; both motions must have same frequencies. otherwise the child
will not swing). According to the Fourier theorem, any oscillatory motions of DNA including very low frequencies can be generated by linear combinations of very fast covalent bond vibrations in DNA and hence can be coupled to slow oscillatory motions of
the environment, e.g., musical sounds. If this view is correct, music can affect, DIRECTLY (i.e., unmediated by the auditory system of the brain), the molecular motions of DNA in every cell in our body. In other words, we can hear music not only through our
ears but also through our whole body including blood. Because of the patent issue, I cannot reveal the experimental evidence supporting this claim, but, indue course, I hope to share with you the scientific evidence we obtained recently. </div>
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In conclusion, it may be that the yin-yang doctrine of the Daoist philosophy (or any other equivalent principles) applies here, since molecular genetics and epigenetics may constitute the irreconcilable opposites: </div>
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"Genetics has two complementary aspects -- molecular genetics and epigenetics."</div>
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"Molecular genetics and epigenetics are the complementary aspects of genetics."</div>
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"Genetic phenomena can be accounted for in two irreconcilably opposite manner with equal validity -- through the bottom-up (or reductionistic) or the top-down (or holistic) approaches."</div>
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The last statement would help avoid many wasteful debates in the field of genetics. </div>
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If you have any questions or corrections, please let me know.</div>
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Sung</div>
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<div id="m_456809759171946012divRplyFwdMsg" dir="ltr"><font face="Calibri, sans-serif" color="#000000" style="font-size:11pt"><b>From:</b> Arthur Wist <<a href="mailto:arthur.wist@gmail.com" target="_blank">arthur.wist@gmail.com</a>><br>
<b>Sent:</b> Friday, April 27, 2018 6:48 PM<br>
<b>To:</b> Sungchul Ji; FIS FIS<br>
<b>Cc:</b> <a href="mailto:sburley@proteomics.rutgers.edu" target="_blank">sburley@proteomics.rutgers.edu</a><wbr>; Sergey Petoukhov; ole2001@med.cornell; <a href="mailto:daniela@shirasawa-acl.net" target="_blank">daniela@shirasawa-acl.net</a>; Sungchul Ji; <a href="mailto:xie@chemistry.harvard.edu" target="_blank">xie@chemistry.harvard.edu</a>; <a href="mailto:nyan@princeton.edu" target="_blank">nyan@princeton.edu</a><br>
<b>Subject:</b> Re: [Fis] Fw: The 'Shirasawa phenomenon' or the 'Shirasawa effect"</font>
<div> </div>
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<div class="m_456809759171946012PlainText">Hi,<br>
<br>
Just a short note to first of all say thank you, I've find this very<br>
helpful to know albeit I can't point to a direct application. Secondly<br>
however, I do wonder: Why & how come you neglected to - in either an<br>
inclusionary or exclusionary manner - address any potential epigenetic<br>
mechanisms?<br>
<br>
Kind regards,<br>
<br>
<br>
Arthur<br>
<br>
On 20 April 2018 at 19:32, Sungchul Ji <<a href="mailto:sji@pharmacy.rutgers.edu" target="_blank">sji@pharmacy.rutgers.edu</a>> wrote:<br>
> Hi,<br>
><br>
><br>
> I am forwarding a slightly modified version of my previous post with the<br>
> same title which was rejected by the FIS list due to the heavy attachments.<br>
> The most significant addition is written in green. The removed attachments<br>
> are now replaced by their web addresses from which they can be downloaded<br>
> free of charge.<br>
><br>
><br>
> Best.<br>
><br>
><br>
> Sung<br>
><br>
> ______________________________<wbr>__<br>
> From: Sungchul Ji<br>
> Sent: Thursday, April 19, 2018 11:02 AM<br>
> To: FIS FIS<br>
> Cc: Sergey Petoukhov; <a href="mailto:daniela@shirasawa-acl.net" target="_blank">daniela@shirasawa-acl.net</a>; John Stuart Reid; sayer ji;<br>
> <a href="mailto:sji.conformon@gmail.com" target="_blank">sji.conformon@gmail.com</a>; <a href="mailto:xie@chemistry.harvard.edu" target="_blank">xie@chemistry.harvard.edu</a>;<br>
> <a href="mailto:sburley@proteomics.rutgers.edu" target="_blank">sburley@proteomics.rutgers.edu</a><wbr>; <a href="mailto:nyan@princeton.edu" target="_blank">nyan@princeton.edu</a><br>
> Subject: The 'Shirasawa phenomenon' or the 'Shirasawa effect"<br>
><br>
><br>
> Hi FISers,<br>
><br>
><br>
> In 2003, Takuji Shirasawa and his coworkers [1] found that mutating certain<br>
> amino acids in the hemoglobin molecule (Hb) in mice produced the following<br>
> effects:<br>
><br>
> (1) increase O_2 consumption and CO_2 production,<br>
><br>
> (2) the conversion of the muscle histology from a fast glycolytic to a fast<br>
> oxidative type,<br>
><br>
> (3) a mild anemia, and<br>
><br>
> (4) faster running speed.<br>
><br>
><br>
> In other words, Shirasawa et al provided a concrete example of molecular<br>
> changes (e.g., amino acid mutations in Hb) leading to (or associated with)<br>
> macroscopic physiological changes in whole animals (e.g., anemia, running<br>
> behavior, etc.). For the convenience of discussions, I am taking the<br>
> liberty of referring to this finding as the "Shirasawa et al.<br>
> phenomenon/effect" or, more briefly, the "Shirasawa phenomenon/effect" which<br>
> may be viewed as the macroscopic version of the Bohr effect [2].<br>
><br>
><br>
> The 'Shirasawa phenomenon/effect' is not limited to hemoglobin. There are<br>
> now many similar phenomena found in the fields of voltage-gated ion<br>
> channels, i.e., molecular changes in the amino acid sequences of ion channel<br>
> proteins leading to (or associated with) macroscopic effects on the human<br>
> body called diseases [3].<br>
><br>
><br>
> Although the current tendency among practicing molecular biologists and<br>
> biophysicists would be to explain away what is here called the Shirasawa<br>
> phenomenon in terms of the microscopic changes "causing" the macroscopic<br>
> phenomenon in a 1:1 basis, another possibility is that the microscopic<br>
> changes "cause" a set of other microscopic changes at the DNA molecular<br>
> level which in turn cause a set of macroscopic changes", in a many-to-many<br>
> fashion.<br>
><br>
><br>
> Current trend: Microscopic change (Hb mutation) ---------> Macroscopic<br>
> change 1 (Oxygen affinity change of blood) ---------> Macroscopic change 2<br>
> (O_2 metabolism, anemia, running behavior)<br>
><br>
><br>
><br>
> Althernative mechanism: Microscopic change 1 (Hb mutation) -------><br>
> Microscopic change 2 (Changes in the standing waves in DNA) -------><br>
> Multiple macroscopic changes (O_2 metabolism, anemia, muscle cell<br>
> histological changes).<br>
><br>
><br>
> The alternative mechanism proposed here seems to me to be more consistent<br>
> with the newly emerging models of molecular genetics [4] and single-molecule<br>
> enzymology [5, 6].<br>
><br>
><br>
><br>
> Since the 'Shirasawa phenomenon/effect' evidently implicates information<br>
> transfer from the microscale to the macroscale, it may be of interest to<br>
> many information theoreticians in this group. If you have any questions,<br>
> comments, or suggestions, please let me know.<br>
><br>
><br>
> All the best.<br>
><br>
><br>
> Sung<br>
><br>
><br>
><br>
> References:<br>
><br>
> [1] Shirasawa, T., et al. (2003). Oxygen Affinity of Hemoglboin<br>
> Regulaters O_2 Comsumtion, Metabolism, and Physical Activity. J. Biol.<br>
> Chem. 278(7): 5035-5043. PDF at<br>
> <a href="https://na01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.jbc.org%2Fcontent%2F278%2F7%2F5035.full.pdf&data=02%7C01%7Csji%40pharmacy.rutgers.edu%7Cb134e6f0f18640a1578608d5ac911871%7Cb92d2b234d35447093ff69aca6632ffe%7C1%7C1%7C636604661553806634&sdata=sNOsN%2BTGxWSKHNzVWNJXDW3dU6tveVfKfNPaV%2Bcv3e4%3D&reserved=0" id="m_456809759171946012LPlnk600653" class="m_456809759171946012OWAAutoLink" target="_blank">
https://na01.safelinks.<wbr>protection.outlook.com/?url=<wbr>http%3A%2F%2Fwww.jbc.org%<wbr>2Fcontent%2F278%2F7%2F5035.<wbr>full.pdf&data=02%7C01%7Csji%<wbr>40pharmacy.rutgers.edu%<wbr>7Cb134e6f0f18640a1578608d5ac91<wbr>1871%<wbr>7Cb92d2b234d35447093ff69aca663<wbr>2ffe%7C1%7C1%<wbr>7C636604661553806634&sdata=<wbr>sNOsN%<wbr>2BTGxWSKHNzVWNJXDW3dU6tveVfKfN<wbr>PaV%2Bcv3e4%3D&reserved=0</a><br>
><br>
> [2] The Bohr effect. <a href="https://na01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fen.wikipedia.org%2Fwiki%2FBohr_effect&data=02%7C01%7Csji%40pharmacy.rutgers.edu%7Cb134e6f0f18640a1578608d5ac911871%7Cb92d2b234d35447093ff69aca6632ffe%7C1%7C1%7C636604661553806634&sdata=T%2Fl5fXUzb4RN0RUwpLBwASDExyceUPasgf%2BaJhmraJw%3D&reserved=0" id="m_456809759171946012LPlnk782278" class="m_456809759171946012OWAAutoLink" target="_blank">
https://na01.safelinks.<wbr>protection.outlook.com/?url=<wbr>https%3A%2F%2Fen.wikipedia.<wbr>org%2Fwiki%2FBohr_effect&data=<wbr>02%7C01%7Csji%40pharmacy.<wbr>rutgers.edu%<wbr>7Cb134e6f0f18640a1578608d5ac91<wbr>1871%<wbr>7Cb92d2b234d35447093ff69aca663<wbr>2ffe%7C1%7C1%<wbr>7C636604661553806634&sdata=T%<wbr>2Fl5fXUzb4RN0RUwpLBwASDExyceUP<wbr>asgf%2BaJhmraJw%3D&reserved=0</a><br>
> [3] Huang W, Liu M, S Yan F, Yan N. (2017). Structure-based assessment<br>
> of disease-related mutations in human voltage-gated sodium channels. Protein<br>
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