BC SCIENCE
Saved by @CodyyyGardner

Today we report the use of base editing in patient-derived cells and in mice to correct the most common cause of progeria, the devastating rapid aging disease. Progeria is typically caused by a dominant negative C•G-to-T•A point mutation in LMNA. 1/11 https://t.co/O7dkEYpndg

 The mutation (discovered by @NIHDirector’s lab in 2003) results in progerin, a toxic protein that damages nuclei. So providing more healthy LMNA is not a solution, and cutting the mutated gene with nucleases is also challenging due to indel mixtures & similarity with wt LMNA.2/11
We used an adenine base editor to convert the T•A that causes progeria back to C•G at the key position in LMNA. Base editing in cells from progeria children corrected the mutation efficiently (~90%) with minimal indels or off-target edits, and restored nuclear morphology. 3/11
We then performed in vivo base editing of a mouse model of human progeria developed by @NIHDirector’s lab. These mice have two copies of the mutated human LMNA gene, and develop heart disease, age rapidly, & die early (~7 mo.), resembling symptoms of the disease in children. 4/11
A single injection of AAV9 (10^11-10^12 total vg) encoding the base editor into the circulatory system of these mice resulted in ~10-60% correction of the mutation in various organs, corrected the RNA missplicing of LMNA, and reduced progerin protein levels in tissues. 5/11
Base editor-treated mice showed profound rescue of aorta pathology. While saline-injected control progeria mice lose >90% of their vascular smooth muscle cells by 6 mo., and accumulate thick fibrosis around the aorta, base editor-treated aortas are normal in these respects. 6/11
Consistent with this rescue of aorta pathology, aortas of base editor-treated mice at 6 mo. show little human progerin, but abundant normal human Lamin A protein in vascular smooth muscle cells by immunofluorescence. 7/11
Control progeria mice had a median lifespan of 215 d. Mice injected with base editor at 14 d (corresponding roughly to a 5-year-old human in maturation level, though not necessarily in disease progression) had a median lifespan of 510 d, approaching “old age” in normal mice. 8/11

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Corey Lynn \U0001f64f\U0001f1fa\U0001f1f8
Corey Lynn 🙏🇺🇸...
@CoreysDigs
1) OBSERVATION: The frequencies are changing. I would have to assess stats on the electromagnetic field to see its fluctuations. All I know is, I am highly sensitive to energy/frequencies, and they are changing, because…

2) 2 Weeks ago, my dog was effected by it as well. He is hearing things that aren’t technically audible. I can tell by his body language and sounds. One week ago I began feeling a pressure in my head and ears. It wasn’t painful at all, but it was intense for a bit.

3) It reminded me of taking off in an airplane a bit. I felt like I was in a vacuum. It went on and off for a couple of days. I’ve picked up on frequencies and high pitched sounds (not audible to most) for 30 years, and today my right ear began to ring for longer than usual.

4) This is nothing unusual for me, with exception of the duration. This happens often with me. No, it’s not tinnitus. Only this time, when I spoke, there was reverb creating a high pitch in my ear from my voice. This lasted for about 30 minutes. It did not hurt, just annoying.

5) So yes, the frequencies are changing. What this means exactly, I am unsure of at the moment. Some will say electromagnetic fields, others will say ascension, and some will say pole shift. I honestly can’t say at this very moment.
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Santa Fe Institute
Santa Fe Institute
@sfiscience
"You don't see radio changing gradually and suddenly become radar. #Darwin's theory doesn't work for #technology, and we have to make a new observation."

- W Brian Arthur at SFI today

#evolution #innovation #invention


"Novel technologies are constructed from existing technologies. These offer themselves as components for the construction of further technologies."

- W Brian Arthur at SFI today

#evolution #innovation #invention #technology #engineering #design


Unlike the two-parent #inheritance typical to (but not ubiquitous among) #complex organisms, #technology inherits features from n parents - a "vast ancestral #network" more like horizontal gene transfer networks in #bacteria.

W Brian Arthur on sumulating #invention on a chip:


Does #Archaeology support the Theory of the #AdjacentPossible - that #innovation is combinatorial, persistent, cumulative?

In short, yes. SFI's Tim Kohler on the #Paleolithic data of #technology #evolution & the #prehistory of the infamous "hockeystick" curve:

😉 @SAPIENS_org


#Economist Roger Koppl of @SyracuseU presents a model for the #AdjacentPossible at SFI.

Output = "a combinatorial explosion" or #singularity, albeit one that arguably occurred millions of years ago, or in the distant future (since the model doesn't specify t = 0):
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Eric Feigl-Ding
Eric Feigl-Ding
@DrEricDing
JUST ONE PERSON—UK 🇬🇧 scientists think one immunocompromised person who cleared virus slowly & only partially wiped out an infection, leaving behind genetically-hardier viruses that rebound & learn how to survive better. That’s likely how #B117 started. 🧵 https://t.co/bMMjM8Hiuz


2) The leading hypothesis is that the new variant evolved within just one person, chronically infected with the virus for so long it was able to evolve into a new, more infectious form.

same thing happened in Boston in another immunocompromised person that was sick for 155 days.

3) What happened in Boston with one 45 year old man who was highly infectious for 155 days straight before he died... is exactly what scientists think happened in Kent, England that gave rise to #B117.


4) Doctors were shocked to find virus has evolved many different forms inside of this one immunocompromised man. 20 new mutations in one virus, akin to the #B117. This is possibly how #B1351 in South Africa 🇿🇦 and #P1 in Brazil 🇧🇷 also evolved.


5) “On its own, the appearance of a new variant in genomic databases doesn’t tell us much. “That’s just one genome amongst thousands every week. It wouldn’t necessarily stick out,” says Oliver Pybus, a professor of evolution and infectious disease at Oxford.
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James Mitchell \u24cb\U0001f42c
James Mitchell Ⓥ🐬...
@MesMitch
The endangered whales must contend with up to 1,000 boats moving daily through an important feeding area in the eastern South Pacific, according to research published in the scientific journal Nature.@WeDontHaveTime
#ForNature @JohnKerry
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Asbj\xf8rn St\xf8ylen
Asbjørn Støylen
@strain_rate
1/ #LBBB generates often a classical pattern on #EchoFirst. The pattern is very distinctive in Tissue Doppler of the septum.


The classical pattern arises from the time lapse of the activation and relaxation of the two walls, creating a pattern of interaction due to a sequence temporal imbalances of the tension between the two walls.


2/ As the septum is activated first, it contracts (shortening - septal flash) without activation of the lateral wall, which stretches. This generates slower pressure build up than a normal IVC, which then is prolonged.


3/ During ejection, the LV volume decreases, so both walls shorten. Tension, however, declines first in the septum, as this was activated first. This leads to a tension imbalance, so the lateral wall continues to shorten, the more relaxed septum stretches.


4/ The stretching of the septum builds up an elastic tension in the septum, which is released as recoil, when tension declines in the lateral wall, showing a post systolic shortening in the septum which is due to elasticity.
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SK
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#DoYouKnow -The place where
Lalitha Sahasranamam -1000 names of Devi originated.

It is in Lalithambigai temple -Thirumeeyachur,Near Mayiladuthurai,TN

There is a Legend #story & it is related to this beautiful #sculpture of Kshetrapuraneswarar & Ambal Lalithambigai #Thread 👇


#Legend #story
It is believed that this is birth place of Kashyapa Maharishi’s sons, Arunan& Garudan. Arunan(charioteer of Surya)was physically handicapped.He was a Shiva devotee.Arunan wanted to visit Kailash to have Shiva Darshan,but Surya Dev denied permission.

So Arunan disguised as a girl & was on his way to Kailash.On the way Surya Dev saw this girl & outraged her modesty.Shiva was very angry with Suryan for misbehaviour & cursed him to get darkened. Whole world plunged into darkness.Surya Dev pleaded to Bhagwan Shiv to forgive him.

Shiva Bhagwan asked him to go to Thirumiyachur & worship him there. As advised, Surya Dev performed rigorous penance, placed murthi of Shiva& Parvathy on an elephant & took them to the clouds.Shiva in this temple is known as Meganathaswamy,Devi is known as Lalithambigai


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SHAKTA DHARMA AND THEIR ACHARYAS

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Agastya learned the secrets of Shri Vidya from Vishnu ji in Hayagriva avtaar. Bhagwan Ram, Laxman and Krishna too learned the tantrik vidya. Even Rig Ved 7.103.5 Sayan Bhasya also mentions about Śhākta/शाक्त(शाक्तस्येव शक्तिमतः).

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Adi Shankaracharya wrote Pramanech saar named book on tantra and Anand lahri book on Devi strotras. Then there were Acharya Shankar, Bhaskar Rai, Laxman, Deshikendra, Raghav Bhatt, Krishnand,
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Did you know?
Ahilyabai Holkar was one of India's
greatest women rulers of all time.

Ahilyabai was Born on May 31,1725 in the village of Chondi,Jamkhed distt,Maharashtra to a man named Mankoji Shinde,who was the Patil(Chief) of a village and a member of proud Dhangar Community.


Despite the fact that girls' education was a farther dream in those days, Ahilyabai was homeschooled by her father.
Ahilya didn't belong to any royal family but in a twist of fate she is still remembered as one of the most revered Queen in the history.


While they were living their humdrum lives, one day Malhar Rao Holkar, commander of the Peshwa Bajirao & Lord of the Malwa stopped in Chondi on his way to Pune, where he couldn't help but notice a young 8yrs old Ahilyabai in the temple service feeding the poor & hungry.

He was so impressed by the sheer innocence&beauty with simplicity character of Ahilyabai dat he asked her hand in marriage for his son Khanderao Holkar.Just like that she got married to Khanderao in 1733 at a tender age of 8&became a bride of esteemed Maratha community of Holkars

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