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David R. Liu
@davidrliu 4 years, 3 months ago 437 views

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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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Kris Postadjian
@KrisP55

A Thread about Famous Armenian Inventors and what we have contributed to the world. So the next time someone wants to say we are unimportant, you can rest easy knowing Armenians have contributed some of the greatest inventions to mankind. Here is a handful but there's more.

Raymond Damadian: Armenian-American Physician and inventor of the first MRI machine. MRI is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. Raymond created the first MRI in 1977.

Artem Mikoyan: One of the most famous engineers in aviation. Mikoyan along with Gurevich created one of the most famous Jet lines in history, the MiG. MiG jets directly competed with American Lockheed Martin F Series planes and were among the first to surpass the speed of sound.

Hovannes Adamian: Most notably laid the foundations of color television with his Tri-Color Principle. His work would go on to become the framework that is used to create Color-TV that we see today. He is recognized as one of the founders of color television.

Emik Avakian: An inventor who unfortunately was disabled, but that didn't stop him from contributing work that would help people similar to his condition. Notable contributions are the automatic wheelchair which dismiss the action of hand rolling and a breath operated typewriter.

Robbie Andrew
@robbie_andrew

"NO LONGER BEST IN THE WORLD"
UNEP's new Human Development Index includes a new (separate) index: Planetary pressures-adjusted HDI (PHDI). News in Norway is that its position drops from #1 to #16 because of this, while Ireland rises from #2 to #1.
Why?

https://t.co/aVraIEzRfh

Check out Norway's 'Domestic Material Consumption'. Fossil fuels are no different here to Ireland's. What's different is this huge 'non-metallic minerals' category.
(Note also the jump in 1998, suggesting data problems.)
https://t.co/5QvzONbqmN

In Norway's case, it looks like the apparent consumption equation (production+imports-exports) for non-metal minerals is dominated by production: extraction of material in Norway.
https://t.co/5QvzONbqmN

And here we see that this production of non-metallic minerals is sand, gravel and crushed rock for construction. So it's about Norway's geology.
https://t.co/y6rqWmFVWc

Norway drops 15 places on the PHDI list not because of its CO₂ emissions (fairly high at 41st highest in the world per capita), but because of its geology, because it shifts a lot of rock whenever it builds anything.

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Adam Hamdy
@adamhamdy

1. I find it remarkable that some medics and scientists aren’t raising their voices to make children as safe as possible. The comment about children being less infectious than adults is unsupported by evidence.

I find it remarkable that a section of society not rejoicing that children very rarely ill with COVID compared to other viruses and much less infectious than adults

Instead trying prove the opposite!

Why??
— Michael Absoud \U0001f499 (@MAbsoud) February 12, 2021

2. @c_drosten has talked about this extensively and @dgurdasani1 and @DrZoeHyde have repeatedly pointed out flaws in the studies which have purported to show this. Now for the other assertion: children are very rarely ill with COVID19.

3. Children seem to suffer less with acute illness, but we have no idea of the long-term impact of infection. We do know #LongCovid affects some children. @LongCovidKids now speaks for 1,500 children struggling with a wide range of long-term symptoms.

4. 1,500 children whose parents found a small campaign group. How many more are out there? We don’t know. ONS data suggests there might be many, but the issue hasn’t been studied sufficiently well or long enough for a definitive answer.

5. Some people have talked about #COVID19 being this generation’s Polio. According to US CDC, Polio resulted in inapparent infection in more than 99% of people. Severe disease occurred in a tiny fraction of those infected. Source:

Duncan J Campbell
@Maven1967

What is going on at SWANSEA UNIVERSITY in Wales?
1.
https://t.co/d5NKtNlxxa
Sounds as if its connected to Bill Gates "LUCIFERASE" Vaccine?

2.
https://t.co/k0w1mjaPg0

"HILLARY RODHAM CLINTON SCHOOL OF LAW"
- AT SWANSEA UNIVERSITY!!!

3.
https://t.co/jifuWq6cGq
Remember all those FIRES, over the Summer!!!

4.
https://t.co/H3lstFyYx8
WUHAN PARTNERSHIP

"Links between Swansea & Wuhan date back to 1855 when Swansea missionary Griffith John founded the Wuhan Union Hospital.
This relationship was strengthened when representatives of the two cities signed an agreement".

5.
https://t.co/5b1JqiEQzi
Swansea University Strengthens Links with China

$JS Oakie\U0001f4dcProtect the 4th Amendment.$

JS Oakie📜Protect the 4...
@OakieJs

I think we have to expand our thinking about the toroidal sphere even more. When looking at maps, I noticed the da Vinci map, from 1514, which uses the Reuleaux Triangle. This triangle is formed from 3 intersecting circles, and is in the center of a trefoil.

The trefoil is the focal point in many gothic structures, repeatedly and prominently shown. It is represented in many ways. ‘Going down the rabbit hole’ now makes sense, if you understand the center point of the ears is the center of the torus, with the rabbit trefoil.

The trefoil can be found within the toroidal field. Here is a fun site, where you can manipulate it yourself. https://t.co/FCMcybuuFC

The wiki page makes it seem like there isn’t much of importance with the Reuleaux Triangle, besides being used for coinage, or some stupid bike. But the Wankel engine is an interesting engine, using this geometric design https://t.co/ayPOgkAqGN

https://t.co/m9EaWwF796

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I want to explain what happened to tumblr overnight. And why Twitter as reached it's dream (or have come ever so close to it)

Yahoo, who bought Tumblr years ago, used to have a huge adult presence on the early net. They allowed adult groups and what not.

However, people and bots (just like now) misused the service, and Yahoo were forced to make a choice. They made private the groups (and later closed them down and sold some of it to other companies) and then ended their chatrooms on yahoo messenger...

after a incident with one of the chatrooms vid cams. The damage was done, Yahoo Messenger lost a lot of people - and with the closing of the groups - backpage and Craigslist came more important.

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신념의사나이...
@Belposto_korea

What does Gold- Backed mean?
The Chinese Elders have been accumulating gold for hundreds of years. They are gold-rich. Some of their gold was loaned to the Central Banking System so that it could fund the rebuilding of Europe after the many war-torn years from World Wars I and II

BTW they never returned it but used it to start their financial empire to enslave humanity. This is the Central Bank Banking System./2

Maybe this is why one of the conditions to use their gold for the QFS is the demise and full disclosure of the Central Bank banking system before the RV can take place./3

The Elders have caves of hidden gold and are now using it to gold-back the currencies in the QFS for every country in the world. It is important to understand that the QFS and the money it is about to release is all brand-new currency./4

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Brian Cates
@drawandstrike

Trump is gonna let the Mueller investigation end all on it's own. It's obvious. All the hysteria of the past 2 weeks about his supposed impending firing of Mueller was a distraction. He was never going to fire Mueller and he's not going to

BREAKING: President Donald Trump has submitted his answers to questions from special counsel Robert Mueller
— Ryan Saavedra (@RealSaavedra) November 20, 2018

Mueller's officially end his investigation all on his own and he's gonna say he found no evidence of Trump campaign/Russian collusion during the 2016 election.

Democrats & DNC Media are going to LITERALLY have nothing coherent to say in response to that.

Mueller's team was 100% partisan.

That's why it's brilliant. NOBODY will be able to claim this team of partisan Democrats didn't go the EXTRA 20 MILES looking for ANY evidence they could find of Trump campaign/Russian collusion during the 2016 election

They looked high.

They looked low.

They looked underneath every rock, behind every tree, into every bush.

And they found...NOTHING.

Those saying Mueller will file obstruction charges against Trump: laughable.

What documents did Trump tell the Mueller team it couldn't have? What witnesses were withheld and never interviewed?

THERE WEREN'T ANY.

Mueller got full 100% cooperation as the record will show.

ashkan soltani
@ashk4n

BREAKING: @CommonsCMS @DamianCollins just released previously sealed #Six4Three @Facebook documents:

Some random interesting tidbits:

1) Zuck approves shutting down platform API access for Twitter's when Vine is released #competition

2) Facebook engineered ways to access user's call history w/o alerting users:

Team considered access to call history considered 'high PR risk' but 'growth team will charge ahead'. @Facebook created upgrade path to access data w/o subjecting users to Android permissions dialogue.

3) The above also confirms @kashhill and other's suspicion that call history was used to improve PYMK (People You May Know) suggestions and newsfeed rankings.

4) Docs also shed more light into @dseetharaman's story on @Facebook monitoring users' @Onavo VPN activity to determine what competitors to mimic or acquire in 2013.

https://t.co/PwiRIL3v9x

Eileen May
@suleskerry

Joanna Cherry:"Alex Salmond secured a concession that nothing in Scotland Act would preclude the people of Scotland from subsequently choosing an independent future. This is recorded in Hansard during second reading of Referendums (Scotland & Wales) Bill, May 21, 1997."

Donald Dewar said: “I should be the last to challenge the sovereignty of the people, or deny them the right to opt for any solution to the constitutional question they wished. For example, if they want to go for independence, I see no reason why they should not do so." JC

"In same debate Alex Salmond went on to emphasise that “… the Claim of Right referred to sovereign right of the Scottish people to determine a form of Govt best suited to their needs. It did not suggest sovereignty resides with English Members of Parliament." Joanna Cherry

Joanna Cherry: "Donald Dewar articulated the democratic norm later enshrined in the Edinburgh Agreement. His concession laid the foundation for the 2014 referendum in recognising the rights of Scots to choose whether to remain part of our voluntary union with England."

"I am wholly in agreement with view that we must find a legal & constitutional way to demonstrate that public opinion in Scotland has changed since 2014 referendum, in order for our independence to be internationally recognised & therefore meaningful." Joanna Cherry