Melatonin, an indoleamine, is a natural compound produced by various organisms, including bacteria and eukaryotes. Its discovery in 1958 by Aaron Lerner and colleagues at Yale Medical School stemmed from the isolation of a substance from the pineal gland of cows that could induce skin lightening (inhibit "melanogenesis") in common frogs.
Since then, a variety of its biological activity was found, including inducing sleep, stimulating immune system, suppressing cancer growth etc, etc. All of these findings stronly suggest that melatonin is a natural PAK1-blocker.
As I have described previously, PAK1 is a kinase, which we found in soil amoeba in 1977, and Ed Maser's team cloned in mammals in 1994.
Around 2007, we found that PAK1-deficient mutant of C. elegans lives 60% longer than the wild-type, and around 2015, we found that melanogenesis depends on PAK1.
Finally, in 2019, Melatonin was found to promote the longevity of C. elegans (as well as mice), proving that this natural hormone is a PAK1-blocking elixir:
REF:
O Karadas, N Ozpinar, E Bilgic et al (2019).
The physiological and lifespan alterations in Caenorhabditis elegans exposed to different dosages of melatonin. Pak J Pharm Sci. 32: 625-630.
For more detail of Melatonin,
read the 1996 book "The Melatonin Miracle" by Walter Pierpaoli et al (published by Simon and Schuster), and 1995 book "Melatonin: Your Body's Natural Wonder Drug" by Russel Reiter et al (published by Bantam Books).
Interestingly, grape peel also contains a PAK1-blocking elixir called "resveratrol" (R3).
Propolis, the oldest remedy that Hippocrates in ancient Greece used, is an ethanol extract of bee hives, containing a PAK1-blocker called "CAPE" which we found inhibits melanogenesis and extends lifespan of C. elegans as well.
Although Vitamin K2 is a potent PAK1-blocking elixir for C. elegans, Vitamin D3 is a rather weak PAK1-blocking elixir, mainly because it is inactivated by CYP21 which hydroxylates at position 21. However, a CYP21-resistant D3 derivative called "MART-10" was developed as an anti-cancer drug by a Japanese team around 2007, and we wonder if this derivative blocks melanogenesis or not. If it does, it would be a very potent elixir...
2025年5月31日土曜日
2025年5月30日金曜日
"2nd Civil War" in US is inevitable as a film at least!
Don't forget the Spirit of "Boston Marathon"!
Climb up the "Heart-Breaking Hill"!
Boston is the Capital for "Democrats"!
Crash the GOP (Trump) 's Capitol (DC)!
Boston was the first US city fighting for "Independence from UK".
Likewise, Boston will lead the Domocrats fighting against Trump's GOP kingdom.
A new "Civil War" between GOP states (DC) and Democrat states (Boston) will be "inevitable"!
Canada might send troops to defend "Boston", while Mexico might send troops to defend "California" as well... Perhaps Denmark might send troops to defend "Greenland", too...
See the detail in "2nd Civil War" (2026 film of MGM, under production!).
This war will certainly be a "conventional" (surely "non-nuclear") war!
Denzel Washington could play the role of a general defending "Boston" for Democrats...
Sebastian Stan might play the role of Trump again as the 2024 film "Apprentice" in which he was nominated for an Oscar.
Bill Gates, an ex-Harvard student, might donate a plenty of money to support this new film...
Perhaps Bill might run even "Heart-Breaking Hill" for 2028 US presidential election as a Democrat candidate....
(Elon Musk's candidacy diminished as Trump's trading tariff led to the bankruptcy of his "TESLA")
At least "Microsoft" users will support Bill. The question is if "Apple" users also are willing to support him or not...
FOOT NOTE:
On Feb. 15, 2025, "Apple" had a market cap of around $3.6 trillion, while "Microsoft" lagged behind it at $3.04 trillion.
Well, Bill has to set up a "well-balanced" policy which would satisfy both customers...
By the way, if I remember correctly, Bill Rogers (not Bill Gates!) won this event (Boston Marathon) four times during 1975-1980, and was the very last "American" male who won this race ("African" Highlanders are too strong to be beaten since then!).
Likewise, Boston will lead the Domocrats fighting against Trump's GOP kingdom.
A new "Civil War" between GOP states (DC) and Democrat states (Boston) will be "inevitable"!
Canada might send troops to defend "Boston", while Mexico might send troops to defend "California" as well... Perhaps Denmark might send troops to defend "Greenland", too...
See the detail in "2nd Civil War" (2026 film of MGM, under production!).
This war will certainly be a "conventional" (surely "non-nuclear") war!
Denzel Washington could play the role of a general defending "Boston" for Democrats...
Sebastian Stan might play the role of Trump again as the 2024 film "Apprentice" in which he was nominated for an Oscar.
Bill Gates, an ex-Harvard student, might donate a plenty of money to support this new film...
Perhaps Bill might run even "Heart-Breaking Hill" for 2028 US presidential election as a Democrat candidate....
(Elon Musk's candidacy diminished as Trump's trading tariff led to the bankruptcy of his "TESLA")
At least "Microsoft" users will support Bill. The question is if "Apple" users also are willing to support him or not...
FOOT NOTE:
On Feb. 15, 2025, "Apple" had a market cap of around $3.6 trillion, while "Microsoft" lagged behind it at $3.04 trillion.
Well, Bill has to set up a "well-balanced" policy which would satisfy both customers...
By the way, if I remember correctly, Bill Rogers (not Bill Gates!) won this event (Boston Marathon) four times during 1975-1980, and was the very last "American" male who won this race ("African" Highlanders are too strong to be beaten since then!).
2025年5月29日木曜日
Support "Academic" War against three "Dictators" :
Trump, Putin and Netanyahu!
"GAZA" is the home for Palestine People, not a "Riviera"!
Netanyahu's War against "GAZA" is clearly the "Genocide!
Thus, it is quite reasonable (justified) for US academics to protest against the Israeli's attack on "GAZA".
It is clearly not "anti-seminism"!
Instead, what Netanyahu is doing against "GAZA" is the basically same as what "Hitler" did against JEWS in Germany (and Poland) during WWII!
In conclusion, those who don't understand the simple equation (Hitler=Trump=Putin=Netanyahu) are "Fools" or "Racists".
I have nothing against Jewish people. Many of my former bosses in US including Ed Korn (1928-2024) at NIH are "Jewish" descendants, who believe in science, instead of god. Amazingly, Ed kept working at NIH till he was 90! Certainly he had a "wisdom" how to enjoy a very long life in good health.
It is clearly not "anti-seminism"!
Instead, what Netanyahu is doing against "GAZA" is the basically same as what "Hitler" did against JEWS in Germany (and Poland) during WWII!
In conclusion, those who don't understand the simple equation (Hitler=Trump=Putin=Netanyahu) are "Fools" or "Racists".
I have nothing against Jewish people. Many of my former bosses in US including Ed Korn (1928-2024) at NIH are "Jewish" descendants, who believe in science, instead of god. Amazingly, Ed kept working at NIH till he was 90! Certainly he had a "wisdom" how to enjoy a very long life in good health.
2025年5月28日水曜日
Contribution of "Harvard" Scholars at NIH leading to our discovery of PAK1 and its blockers, "longevity" promoters
In an early 1970s, Bob Adelstein (1934-2024) and Tom Pollard, both graduates from Harvard Medical School, isolated myosin from human platelets.
Then Tom joined Ed Korn's lab at NIH to isolate a single-headed myosin (Myosin I) from a soil amoeba, and found that actin-activation of Myosin I ATPase requires a third factor. In 1975, Bob's team then found that actin-activation of platelet myosin requires a kinase that phosphorylates the light chain of myosin.
Meanwhile I joined Ed Korn's lab in 1974, and eventually found that the amoeba cofactor is myosin I heavy chain kinase, later called PAK1 (RAC/CDC42-activated kinase 1).
In 1994, Ed Manser's team at Singapore University cloned a "mammalian" PAK1 which is activated by two G proteins called RAC and CDC42. Then late 1990s, in collaboration with Ed Manser, our team in Melbourne found that PAK1 is essential for RAS-induced malignant transformation. Finally in 2007, we found that PAK1-deficient mutant of C. elegans lives 60% longer than the wild-type. Meanwhile, since the beginning of this century, we identified a series of natural or synthetic PAK1-blockers which cure cancers and many other diseases, eventually promoting our longevity.
Furthermore, around 2015, we established that inhibition of serum/MITF-dependent melanogenesis in B16F10 melanoma cells is the "quickest" screening criteria for PAK1-blockers.
Thus, we should greatly appreciate the "pioneer" contribution of two "Harvard" scholars (Bob and Tom) at NIH that was done a half-century ago...
In addition, in 2000, a Harvard's team (at Children's Hospital) led by Steve Harrison establisged a Xray-crystal structure of PAK1, facilitating the designing of PAK1-inhibitors:
Lei M, Lu W, Meng W, et al (2000).
Structure of PAK1 in an autoinhibited conformation reveals a multistage activation switch. Cell. 102(3):387-97.
Indeed, in 2002, we managed to find the "first" synthetic PAK1-inhibitor called CEP-1347, which selectively binds the "inactive" homodimer of this kinase:
Nheu TV, He H, Hirokawa Y et al (2002).
The K252a derivatives, inhibitors for the PAK/MLK kinase family selectively block the growth of RAS transformants. Cancer J. 8(4):328-36.
In 1994, Ed Manser's team at Singapore University cloned a "mammalian" PAK1 which is activated by two G proteins called RAC and CDC42. Then late 1990s, in collaboration with Ed Manser, our team in Melbourne found that PAK1 is essential for RAS-induced malignant transformation. Finally in 2007, we found that PAK1-deficient mutant of C. elegans lives 60% longer than the wild-type. Meanwhile, since the beginning of this century, we identified a series of natural or synthetic PAK1-blockers which cure cancers and many other diseases, eventually promoting our longevity.
Furthermore, around 2015, we established that inhibition of serum/MITF-dependent melanogenesis in B16F10 melanoma cells is the "quickest" screening criteria for PAK1-blockers.
Thus, we should greatly appreciate the "pioneer" contribution of two "Harvard" scholars (Bob and Tom) at NIH that was done a half-century ago...
In addition, in 2000, a Harvard's team (at Children's Hospital) led by Steve Harrison establisged a Xray-crystal structure of PAK1, facilitating the designing of PAK1-inhibitors:
Lei M, Lu W, Meng W, et al (2000).
Structure of PAK1 in an autoinhibited conformation reveals a multistage activation switch. Cell. 102(3):387-97.
Indeed, in 2002, we managed to find the "first" synthetic PAK1-inhibitor called CEP-1347, which selectively binds the "inactive" homodimer of this kinase:
Nheu TV, He H, Hirokawa Y et al (2002).
The K252a derivatives, inhibitors for the PAK/MLK kinase family selectively block the growth of RAS transformants. Cancer J. 8(4):328-36.
2025年5月26日月曜日
Harvard vs Trump in the US: David vs Goliath !?
We, scholars, need "magic bullets" to hit between his eyes, not ears, to stop the "Brain Drain" from the US!
Otherwise, US is no longer the "academic" center of the world!
Regarding "PAK" (pathogenic/ageing kinase) research at least, US is no longer its center, since I left US in 1980s to Melbourne. Australia and Singapore are the major driving forces in this field. By blocking this kinase we are able to promote healthy longevity.
In other words, natural or synthetic PAK-blockers will be among "magic bullets" for our intelligency and healthy life.
Neither Trump (in the US) or Putin (in Russia) has a brain to understand PAK research. Thus, it is most probable that both shall extinct before the rest of us.
Back in 1909, a Jewish German chemist (and a Nobel laureate) called Paul Ehrlich developed the first "magic bullet" called "Salvarvan"which selectively kills the bacteria causing Syphilis.
He once quoted: Greediness and stupidity are among the most incurable brain diseases.
Warning:
The American "Mob" democracy created the worst monster in their history, called Trump, which is equivalent to "Hitler".
A new "Magic Bullet" for US Revolution:
Reject to pay the "federal tax" to the Trump administration, and instead donate the tax to Harvard University and other universities or organizations that reject Trump.
We shall set up a new (alternative) FED government in Harvard campus, Cambridge, Boston (instead of Washington, DC).
Eventually, US should be devided into two countries, States for "Fool" (SF) and those for "Wise" (SW), because "F" and "W" cannot live together peacefully any longer, as the gap between these two populations became too wide!
I shall remind you that the very criteria distinguishing between "F" and "W" is not the IQ level. It depends on whether he or she has the "common sense". US (United States) was born in 1776, liberated from UK (United Kingdom), based on the common sense (every human beings are equal). Unfortunately, during 1850s, US was divided into "North" and "South" dependending whether or not people accept the "slavery" system. Eventually the common sense won!
How the rest of the world should respond to the "SF"?
If "SF" keeps fighting against "SW" only, the rest of the world would not interfere with the "domestic" US business. However, once "SF" raises either "trading" or "military" wars against the rest of the world, we shall unite each other to demolish the "SF".
In other words, natural or synthetic PAK-blockers will be among "magic bullets" for our intelligency and healthy life.
Neither Trump (in the US) or Putin (in Russia) has a brain to understand PAK research. Thus, it is most probable that both shall extinct before the rest of us.
Back in 1909, a Jewish German chemist (and a Nobel laureate) called Paul Ehrlich developed the first "magic bullet" called "Salvarvan"which selectively kills the bacteria causing Syphilis.
He once quoted: Greediness and stupidity are among the most incurable brain diseases.
Warning:
The American "Mob" democracy created the worst monster in their history, called Trump, which is equivalent to "Hitler".
A new "Magic Bullet" for US Revolution:
Reject to pay the "federal tax" to the Trump administration, and instead donate the tax to Harvard University and other universities or organizations that reject Trump.
We shall set up a new (alternative) FED government in Harvard campus, Cambridge, Boston (instead of Washington, DC).
Eventually, US should be devided into two countries, States for "Fool" (SF) and those for "Wise" (SW), because "F" and "W" cannot live together peacefully any longer, as the gap between these two populations became too wide!
I shall remind you that the very criteria distinguishing between "F" and "W" is not the IQ level. It depends on whether he or she has the "common sense". US (United States) was born in 1776, liberated from UK (United Kingdom), based on the common sense (every human beings are equal). Unfortunately, during 1850s, US was divided into "North" and "South" dependending whether or not people accept the "slavery" system. Eventually the common sense won!
How the rest of the world should respond to the "SF"?
If "SF" keeps fighting against "SW" only, the rest of the world would not interfere with the "domestic" US business. However, once "SF" raises either "trading" or "military" wars against the rest of the world, we shall unite each other to demolish the "SF".
2025年5月22日木曜日
Atherton Hill Walks: Planned on July 12 (Sat), Starting at 9:30 am, ca 4 km,
Changing the "start line" : "Table Tennnis Center" at 21 Viola Street
Course: Walking through Loder Street (LS) at the top of hill, via Route 52, Post Office (PO), via Route 1, back to 21 Viola Street (VS).
Eligibility of Participants: age over 11, and able to finish this course (ca 4 km) in 60 min
All finishers will get at least "water" at the finish line, and perhaps the first 8 finishers might get an English Muffin (blue berry) as well.
The main aim: promoting your health by walking up and down the hill within our residential area, safely without crossing the main roads.
Organizer: Atherton Table Tennis (TT) Center
E-Mail address: mogumaruta123@gmail.com
NOTE:
If it rains, the event will be cancelled or postposed !
Eligibility of Participants: age over 11, and able to finish this course (ca 4 km) in 60 min
All finishers will get at least "water" at the finish line, and perhaps the first 8 finishers might get an English Muffin (blue berry) as well.
The main aim: promoting your health by walking up and down the hill within our residential area, safely without crossing the main roads.
Organizer: Atherton Table Tennis (TT) Center
E-Mail address: mogumaruta123@gmail.com
NOTE:
If it rains, the event will be cancelled or postposed !
2025年5月21日水曜日
英国ケンブリッジ大学 (物理学 科) 級の入試問題 (難問) ：
赤と緑 (補色) の絵の具を混ぜると、真っ黒になるが、赤い光と緑の光を混ぜると、黄色に見える。 さて、 黄色の光線に何色の光線を当てると、無色 (白色) に見えるか？
プリズムを使用して、太陽光線 (無色) を七色の虹に分解した ニュートンは、1672年頃、その正解を知っているはず。。。
ケンブリッジ大学の物理/天文学者 "ニュートン" (1643-1727) は、りんごの実が木から落下するのを見て、重力を含めて「万有引力」の存在を発見したので、有名。
実は、つい最近, 我が輩は, 新しい家の 垣根 (立板)を黄色と、 もう一つの色のペンキで、交互に塗っていくと、遠方から、斜めに垣根を眺めると、反射光が「白色」に輝く事を発見！
この難問の答えになる「ヒント」は, 下記の (子供向け) サイトにある：
https://www.kepco.co.jp/sp/energy_supply/energy/kids/science/topic13.html
つまり、"光の3原色" を合わせると、"白色" (無色) になる！
ケンブリッジ大学の物理/天文学者 "ニュートン" (1643-1727) は、りんごの実が木から落下するのを見て、重力を含めて「万有引力」の存在を発見したので、有名。
実は、つい最近, 我が輩は, 新しい家の 垣根 (立板)を黄色と、 もう一つの色のペンキで、交互に塗っていくと、遠方から、斜めに垣根を眺めると、反射光が「白色」に輝く事を発見！
この難問の答えになる「ヒント」は, 下記の (子供向け) サイトにある：
https://www.kepco.co.jp/sp/energy_supply/energy/kids/science/topic13.html
つまり、"光の3原色" を合わせると、"白色" (無色) になる！
登録:
投稿 (Atom)