Toggle light / dark theme

Progress.


Replacing or editing disease-causing mutations holds great promise for treating many human diseases. Yet, delivering therapeutic genetic modifiers to specific cells in vivo has been challenging, particularly in large, anatomically distributed tissues such as skeletal muscle. Here, we establish an in vivo strategy to evolve and stringently select capsid variants of adeno-associated viruses (AAVs) that enable potent delivery to desired tissues. Using this method, we identify a class of RGD motif-containing capsids that transduces muscle with superior efficiency and selectivity after intravenous injection in mice and non-human primates. We demonstrate substantially enhanced potency and therapeutic efficacy of these engineered vectors compared to naturally occurring AAV capsids in two mouse models of genetic muscle disease. The top capsid variants from our selection approach show conserved potency for delivery across a variety of inbred mouse strains, and in cynomolgus macaques and human primary myotubes, with transduction dependent on target cell expressed integrin heterodimers.

That fossil wasn’t enough to confirm Africa as our homeland. Since that discovery, paleoanthropologists have amassed many thousands of fossils, and the evidence over and over again has pointed to Africa as our place of origin. Genetic studies reinforce that story. African apes are indeed our closest living relatives, with chimpanzees more closely related to us than to gorillas. In fact, many scientists now include great apes in the hominid family, using the narrower term “hominin” to refer to humans and our extinct cousins.

In a field with a reputation for bitter feuds and rivalries, the notion of humankind’s African origins unifies human evolution researchers. “I think everybody agrees and understands that Africa was very pivotal in the evolution of our species,” says Charles Musiba, a paleoanthropologist at the University of Colorado Denver.

Paleoanthropologists have sketched a rough timeline of how that evolution played out. Sometime between 9 million and 6 million years ago, the first hominins evolved. Walking upright on two legs distinguished our ancestors from other apes; our ancestors also had smaller canine teeth, perhaps a sign of less aggression and a change in social interactions. Between about 3.5 million and 3 million years ago, humankind’s forerunners ventured beyond wooded areas. Africa was growing drier, and grasslands spread across the continent. Hominins were also crafting stone tools by this time. The human genus, Homo, arrived between 2.5 million and 2 million years ago, maybe earlier, with larger brains than their predecessors. By at least 2 million years ago, Homo members started traveling from Africa to Eurasia. By about 300,000 years ago, Homo sapiens, our species, emerged.

Cumrun Vafa is a theoretical physicist at Harvard. Please support this podcast by checking out our sponsors:
- Headspace: https://headspace.com/lex to get free 1 month trial.
- The Jordan Harbinger Show: https://www.youtube.com/thejordanharbingershow.
- Squarespace: https://lexfridman.com/squarespace and use code LEX to get 10% off.
- Allform: https://allform.com/lex to get 20% off.

CORRECTIONS:
- I’m currently hiring folks to help me with editing and image overlays so there may be some errors in overlays (as in this episode) as we build up a team. I ask for your patience.
- At 1 hour 27 minute mark, we overlay an image of Brian Greene. We meant to overlay an image of Michael Green, an early pioneer of string theory: https://bit.ly/michael-green-physicist.
- The image overlay of the heliocentric model is incorrect.

EPISODE LINKS:
Cumrun’s Twitter: https://twitter.com/cumrunv.
Cumrun’s Website: https://www.cumrunvafa.org.
Puzzles to Unravel the Universe (book): https://amzn.to/3BFk5ms.

PODCAST INFO:
Podcast website: https://lexfridman.com/podcast.
Apple Podcasts: https://apple.co/2lwqZIr.
Spotify: https://spoti.fi/2nEwCF8
RSS: https://lexfridman.com/feed/podcast/
Full episodes playlist: https://www.youtube.com/playlist?list=PLrAXtmErZgOdP_8GztsuKi9nrraNbKKp4
Clips playlist: https://www.youtube.com/playlist?list=PLrAXtmErZgOeciFP3CBCIEElOJeitOr41

OUTLINE:
0:00 — Introduction.
1:51 — Difference between math and physics.
4:34 — Evolution of quantum mechanics.
7:52 — Can mathematics lead humanity off track.
8:51 — Beauty in mathematics.
14:10 — Philosophers using symmetry.
20:04 — How can ancient geometry be used to understand reality.
23:16 — Key ideas in the history of physics.
26:09 — Einstein’s special relativity.
29:46 — Physicists building intuition.
37:44 — Best work by Einstein.
39:28 — Quantum mechanics.
49:30 — Quantum gravity.
51:45 — String theory.
1:07:54 — 10th Dimension.
1:14:32 — Skepticism regarding string theory.
1:25:37 — Key figures in string theory.
1:29:56 — String Theory’s Nobel Prize.
1:33:01 — Edward Witten.
1:41:39 — String Theory Landscape & Swamplands.
1:50:29 — Theories of everything.
2:04:55 — Advice for young people.
2:07:57 — Death.

SOCIAL:

Circa 2014


New collaborative research published in the journal Nature Communications by scientists from Japan, Russia and the US contains the genetic analysis on a species of African midge, which can survive a wide array of extreme conditions including large variations in temperature, extreme drought and even airless vacuums such as space. The team successfully deciphered the genetic mechanism that makes the midge invulnerable to these harsh conditions. Prof. Noriyuki Satoh and Dr. Takeshi Kawashima of Prof. Satoh’s Marine Genomics Unit, as well as Prof. Alexander Mikeyhev of the Ecology and Evolution Unit, and Mr. Manabu Fujie and Dr. Ryo Koyanagi of the DNA Sequencing Section at the Okinawa Institute of Science and Technology Graduate University have contributed to the collaboration.

The midge, Polypedilum vanderplanki, is capable of anhydrobiosis, a unique state that allows an organism to survive even after losing 97% of its body water. Anhydrobiotic organisms are also able to survive other severe conditions such as extreme temperatures ranging from 90°C to-270°C, vacuums and high doses of radiation; all of which would be lethal to most other life forms.

The midge found in northern Nigeria lives in an environment where the dry season lasts for at least six months and droughts can last up to eight months. By the time eggs have hatched and larvae have developed, the pools of water they breed in have dried up. However these dried larvae can survive in this dehydrated state for more than 17 years. “This is a very interesting kind of phenomena,” remarks Prof. Satoh. “The first descriptions of this midge were more than 60 years ago… But serious research started only ten years ago.”

What might happen after the Cybernetic Singularity? Can we refine our theological philosophies in light of new evidence? Are we alone in the Universe? Can you achieve Cybernetic Immortality? When and how can we transcend the human condition? These are some of the questions addressed in my new book THEOGENESIS: Transdimensional Propagation & Universal Expansion. This awe-inspiring volume is to be released on October 1 2021 as part of The Cybernetic Theory of Mind series and is available now to pre-order on Amazon. #THEOGENESIS #TransdimensionalPropagation #UniversalExpansion #CyberneticTheoryofMind #cybernetics #theology #futurism #posthumanism


Ecstadelic Media Group announces the release of the next book in The Cybernetic Theory of Mind series by Alex M. Vikoulov ― THEOGENESIS: Transdimensional Propagation & Universal Expansion ― available as a Kindle eBook on Amazon.

Half-billion-year-old critter belonged to an extinct group of animals.


Palaeontologists have dug up a brand new animal species from the Cambrian era, more than 500 million years ago. Remarkably, Titanokorys gainesi was about half a metre long – which is giant compared to most of the other, pinky-finger-sized species alive at the time.

“The sheer size of this animal is absolutely mind-boggling,” says Jean-Bernard Caron, from the Royal Ontario Museum (ROM) in Canada. “This is one of the biggest animals from the Cambrian period ever found.”

The Cambrian period spanned from around 541 to 485 million years ago. It was a critical time in the evolution of life on Earth because it marked a massive explosion in diversity, with most of the major groups of animals we know today emerging, from arthropods and molluscs to echinoderms and chordates (us).

Summary: Researchers have identified 2,000 genes in humans linked to longevity. The genes are associated with biological mechanisms that drive the prolongation of life in mammals, including DNA repair, coagulation, and immune response.

Source: UPF Barcelona.

What determines the life expectancy of each species? This is a fundamental and highly complex question that has intrigued the field of research throughout history. From the evolutionary point of view, the major cause of these differences between species lies in their ecological adaptations. For example, life expectancy is longer in species adapted to living in trees, underground, or with large body mass, since all these adaptations reduce mortality by predation.

A cancer vaccine could be an effective way to prevent cancer from evolving and becoming resistant to treatment, new research suggests.

Scientists were investigating the use of a cancer-killing virus in clinical trials, and observed, as they had also seen in mice, that although some patients initially responded to the treatment, their tumours soon became resistant.

The researchers showed that the specific mutations causing tumour cells to become resistant to the viral treatment, could be anticipated and exploited using a vaccine which, when tested in mice, was shown to trigger the immune system to destroy treatment resistant tumour cells.


Scientists have developed a cancer vaccine that in mice was shown to trigger the immune system to destroy treatment-resistant tumor cells.