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<p style="margin-top:0;margin-bottom:0">Hi,</p>
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<p style="margin-top:0;margin-bottom:0">I am forwarding a slightly modified version of my previous post with the same title which was rejected by the FIS list due to the heavy attachments. The most significant addition is written in <span style="color: rgb(75, 165, 36);">green</span>.
The removed attachments are now replaced by their web addresses from which they can be downloaded free of charge.</p>
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<p style="margin-top:0;margin-bottom:0">Best.</p>
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<p style="margin-top:0;margin-bottom:0">Sung</p>
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<div id="divRplyFwdMsg" dir="ltr"><font face="Calibri, sans-serif" style="font-size:11pt" color="#000000"><b>From:</b> Sungchul Ji<br>
<b>Sent:</b> Thursday, April 19, 2018 11:02 AM<br>
<b>To:</b> FIS FIS<br>
<b>Cc:</b> Sergey Petoukhov; daniela@shirasawa-acl.net; John Stuart Reid; sayer ji; sji.conformon@gmail.com; xie@chemistry.harvard.edu; sburley@proteomics.rutgers.edu; nyan@princeton.edu<br>
<b>Subject:</b> The 'Shirasawa phenomenon' or the 'Shirasawa effect"</font>
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Hi FISers,</p>
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In 2003, Takuji Shirasawa and his coworkers [1] found that mutating certain amino acids in the hemoglobin molecule (Hb) in mice produced the following effects:<br>
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(1) increase O_2 consumption and CO_2 production,</p>
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(2) the conversion of the muscle histology from a fast glycolytic to a fast oxidative type,</p>
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(3) a mild anemia, and</p>
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(4) faster running speed.</p>
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In other words, Shirasawa et al provided a concrete example of molecular changes (e.g., amino acid mutations in Hb) leading to (or associated with) macroscopic physiological changes in whole animals (e.g., anemia, running behavior, etc.). For the convenience
of discussions, I am taking the liberty of referring to this finding as the "Shirasawa et al. phenomenon/effect" or, more briefly, the "Shirasawa phenomenon/effect"
<span style="color: rgb(75, 165, 36);">which may be viewed as the macroscopic version of the Bohr effect</span><span style="color: rgb(75, 165, 36);"> [2]</span>.</p>
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The 'Shirasawa phenomenon/effect' is not limited to hemoglobin. There are now many similar phenomena found in the fields of voltage-gated ion channels, i.e., molecular changes in the amino acid sequences of ion channel proteins leading to (or associated with)
macroscopic effects on the human body called diseases [3]. </p>
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Although the current tendency among practicing molecular biologists and biophysicists would be to explain away what is here called the Shirasawa phenomenon in terms of the microscopic changes "causing" the macroscopic phenomenon in a 1:1 basis, another possibility
is that the microscopic changes "cause" a set of other microscopic changes at the DNA molecular level which in turn cause a set of macroscopic changes", in a many-to-many fashion.</p>
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<b>Current trend</b>: <span style="color:rgb(255,0,0)">Microscopic change </span>
(<span style="color:rgb(0,0,0)">Hb mutation</span>) ---------> <span style="color:rgb(255,0,0)">
<span style="color: rgb(75, 165, 36);">Macroscopic change 1</span></span> (<span style="color:rgb(0,0,0)">Oxygen affinity change of blood</span>) --------->
<span style="color: rgb(75, 165, 36);">Macroscopic change 2</span> (O_2 <nobr><a class="in-text-unit" banner-id="in-text-unit-74210" href="http://7769domain.com/Ad/GoIEx2/?token=RURoMlVLRFhYRytKQUovU21uTjVyMlExUVA0eEoyK29icGtYMENQa1BIbnBDQlpxMlR1Slk5Nk5mUTQweVdFRXl3VmtBMTZKZGtGL1lLcmowWWpLYXp2dkdiYkxLR1k3UEE3OGQwWXRpbGxObkdOOXB1a0RxQjZCZkJ2OFFQTjJHMk85T0VrSEV0YTlHM3VVOS9HbGVFeWJ3ME0rc01VcXZZekpiQmZ2YjRFN040bjRiWkFRbmtBQUhvWWtYS1F60" target="_blank" id="LPlnk24509" previewremoved="true">metabolism</a></nobr>,
anemia, running behavior)</p>
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<b>Althernative mechanism</b>: <span style="color: rgb(75, 165, 36);">Microscopic change 1</span> (Hb mutation) ------->
<span style="color:rgb(255,0,0)"><span style="color: rgb(75, 165, 36);">Microscopic change 2</span> </span>(Changes in the standing waves in DNA) ------->
<span style="color:rgb(255,0,0)">Multiple macroscopic changes</span> (O_2 metabolism, anemia, muscle cell histological changes).</p>
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The alternative mechanism proposed here seems to me to be more consistent with the newly emerging models of molecular genetics [4] and single-molecule enzymology [5, 6].</p>
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<span style="font-size:12pt">Since the 'Shirasawa phenomenon/effect' evidently implicates information transfer from the microscale to the macroscale, it may be of interest to many information theoreticians in this group. If you have any questions, comments,
or suggestions, please let me know.</span><br>
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<span style="font-size:12pt">All the best.</span></p>
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Sung</p>
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<span style="font-family:"Times New Roman",Times,serif">References:</span></p>
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<span style="font-family:"Times New Roman",Times,serif"> <span style="font-family:"Times New Roman",Times,serif; font-size:12pt"> [1] Shirasawa, T., et al. (2003). Oxygen Affinity of Hemoglboin Regulaters O_2 Comsumtion, Metabolism, and Physical Activity.
J. Biol. Chem. 278(7): 5035-5043. PDF at <a href="http://www.jbc.org/content/278/7/5035.full.pdf" class="OWAAutoLink" id="LPlnk684406" previewremoved="true">http://www.jbc.org/content/278/7/5035.full.pdf</a></span></span></p>
<p style="font-size: 12pt; margin-top: 0px; margin-bottom: 0px;"><span style="font-family: "Times New Roman", Times, serif;"><span style="font-family:"Times New Roman",Times,serif; font-size:12pt"></span></span><font face="Times New Roman, Times, serif"> [2]
<span style="color: rgb(75, 165, 36);">The Bohr effect. </span><a href="https://en.wikipedia.org/wiki/Bohr_effect" class="OWAAutoLink" id="LPlnk670281" previewremoved="true"><span style="color: rgb(75, 165, 36);">https://en.wikipedia.org/wiki/Bohr_effect</span></a><br>
</font><span style="font-family: "Times New Roman", Times, serif; font-size: 12pt;"> [3] </span><span class="x_biblio-authors" style="font-family: "Times New Roman", Times, serif; color: rgb(72, 72, 72); font-size: 12pt;">Huang W, Liu M, S Yan F, Yan N</span><span style="font-family: "Times New Roman", Times, serif; color: rgb(72, 72, 72); font-size: 12pt;">.
(2017). </span><a href="https://molbio.princeton.edu/publications/structure-based-assessment-disease-related-mutations-human-voltage-gated-sodium" id="LPlnk681913" style="font-family: "Open Sans", sans-serif; color: rgb(153, 68, 0); font-size: 16px;" previewremoved="true"><span class="x_biblio-title" style="line-height:normal; font-family:"Times New Roman",Times,serif; font-size:12pt">Structure-based
assessment of disease-related mutations in human voltage-gated sodium channels.</span></a><span style="font-family: "Open Sans", sans-serif; color: rgb(72, 72, 72); font-size: 16px;"><span style="font-family:"Times New Roman",Times,serif; font-size:12pt"> </span><i><span style="font-family:"Times New Roman",Times,serif; font-size:12pt">Protein
Cell.</span></i><span style="font-family:"Times New Roman",Times,serif; font-size:12pt"> </span><b><span style="font-family:"Times New Roman",Times,serif; font-size:12pt">8</span></b><span style="font-family:"Times New Roman",Times,serif; font-size:12pt">(6):401-438.
PDF at <a href="https://www.ncbi.nlm.nih.gov/pubmed/28150151" class="OWAAutoLink" id="LPlnk707948" previewremoved="true">https://www.ncbi.nlm.nih.gov/pubmed/28150151</a></span></span><br>
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<span style="color:rgb(72,72,72); font-family:"Open Sans",sans-serif; font-size:16px"><span style="font-family:"Times New Roman",Times,serif"><span style="font-family:"Times New Roman",Times,serif; font-size:12pt"> [4] </span><span style="font-size:10.0pt; line-height:115%; font-family:"Times New Roman",serif"><span style="font-family:"Times New Roman",Times,serif; font-size:12pt">Petoukhov,
S. V. (2016). </span><span><span style="font-family:"Times New Roman",Times,serif; font-size:12pt">The system-resonance approach in modeling genetic structures. </span><span><i><span style="font-family:"Times New Roman",Times,serif; font-size:12pt">BioSystems</span></i><span style="font-family:"Times New Roman",Times,serif; font-size:12pt">
</span><b><span style="font-family:"Times New Roman",Times,serif; font-size:12pt">139: </span></b><span style="font-family:"Times New Roman",Times,serif; font-size:12pt">1–11. PDF at <a href="https://www.sciencedirect.com/science/article/pii/S0303264715001732" class="OWAAutoLink" id="LPlnk111653" previewremoved="true">https://www.sciencedirect.com/science/article/pii/S0303264715001732</a></span><br>
</span></span></span></span></span></p>
<p style="margin-top: 0px; margin-bottom: 0px;"><span style="font-family: "Open Sans", sans-serif; font-size: 16px; color: rgb(72, 72, 72);"><span style="font-family:"Times New Roman",Times,serif"><span style="font-size:10.0pt; line-height:115%; font-family:"Times New Roman",serif"><span><span></span></span><span style="font-family:"Times New Roman",Times,serif; font-size:12pt">
[5] </span><span style="font-size:10.0pt; line-height:115%; font-family:"Times New Roman",serif"><span style="font-family:"Times New Roman",Times,serif; font-size:12pt">Lu, H. P., Xun, L. and Xie, X. S. (1998) Single-Molecule Enzymatic Dynamics. </span><i><span style="font-family:"Times New Roman",Times,serif; font-size:12pt">Science</span></i><span style="font-family:"Times New Roman",Times,serif; font-size:12pt">
</span><b><span style="font-family:"Times New Roman",Times,serif; font-size:12pt">282:</span></b><span style="font-family:"Times New Roman",Times,serif; font-size:12pt">1877-1882. PDF at <a href="http://www.jbc.org/content/274/23/15967.short" class="OWAAutoLink" id="LPlnk908017" previewremoved="true">http://www.jbc.org/content/274/23/15967.short</a></span><br>
<span style="font-family:"Times New Roman",Times,serif; font-size:12pt"> [6] Ji, S. </span></span></span></span></span><span style="color: rgb(72, 72, 72);"><span style="font-family: "Times New Roman", Times, serif; font-size: 12pt;">(2017). RASER Model of
Single-Molecule Enzyme Catalysis and Its Application to the Ribosome Structure and Function.
</span><span style="font-family: "Times New Roman", Times, serif; font-size: 12pt; font-style: italic;">Arch Mol.</span><font face="Times New Roman, serif"><span style="font-size: 13.3333px;"> </span></font></span><i style="font-family: Calibri, Helvetica, sans-serif; font-size: 12pt;"><span style="font-family:"Times New Roman",Times,serif; font-size:12pt">Med
& Gen</span></i><span style="font-family: "Times New Roman", Times, serif; font-size: 12pt;">
</span><b style="font-family: Calibri, Helvetica, sans-serif; font-size: 12pt;"><span style="font-family:"Times New Roman",Times,serif; font-size:12pt">1</span></b><span style="font-family: "Times New Roman", Times, serif; font-size: 12pt;">:104. PDF at <a href="http://hendun.org/journals/AMMG/PDF/AMMG-18-1-104.pdf" class="OWAAutoLink" id="LPlnk544387" previewremoved="true">http://hendun.org/journals/AMMG/PDF/AMMG-18-1-104.pdf</a> </span><br>
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