LLMs push the boundaries of fully automated variant classification, performing on par with human experts.
Category: genetics – Page 6
Transhumanism: Should We Become More Than Human?
In the future, humanity may embrace genetic engineering and cybernetic augmentation of mind and body, but what does this Transhuman future look like? And should we embrace or resist these paths?
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/ discord Credits: Transhumanism & Humanity’s Future Science & Futurism with Isaac Arthur Episode 375, December 29, 2022 Written, Produced & Narrated by Isaac Arthur Editors: Briana Brownell Donagh Broderick Keith Blockus Lukas Konecny Graphics: Jeremy Jozwik Ken York of YD Visual Music Courtesy of Epidemic Sound http://epidemicsound.com/creator.
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Credits:
Transhumanism \& Humanity’s Future.
Science \& Futurism with Isaac Arthur.
Episode 375, December 29, 2022
Written, Produced \& Narrated by Isaac Arthur.
Editors:
Briana Brownell.
Donagh Broderick.
Keith Blockus.
Lukas Konecny.
Graphics:
Jeremy Jozwik.
Ken York of YD Visual.
Music Courtesy of Epidemic Sound http://epidemicsound.com/creator
Vulnerable ALS neurons reveal molecular warning signs before cell death begins
A new study from the Knight Initiative for Brain Resilience researchers may help explain an enduring mystery about amyotrophic lateral sclerosis (ALS): why the disease kills off some of the brain and spinal cord’s movement-controlling neurons while others show greater resilience.
As ALS progresses, more and more of those motor neurons degenerate and die. As a result, patients lose control of their bodies and become unable to breathe. Many people are diagnosed in middle to late adulthood, and most survive only three to five years after diagnosis.
“It’s a cruelly rapid disease,” said Olivia Gautier, a postdoctoral scholar in the lab of Knight Initiative researcher Aaron Gitler, the Stanford Medicine Basic Science Professor and a professor of genetics at Stanford Medicine.
The Revolving Door of Adenovirus Cell Entry: Not All Pathways Are Equal
An interesting review on adenoviral cell entry and trafficking. Its discussion of how species B adenoviruses tolerate lower endosomal pH and accumulate in later-endosomal compartments before escaping were particularly intriguing. Link.
Adenoviruses represent exceptional candidates for wide-ranging therapeutic applications, from vectors for gene therapy to oncolytics for cancer treatments. The first ever commercial gene therapy medicine was based on a recombinant adenovirus vector, while most recently, adenoviral vectors have proven critical as vaccine platforms in effectively controlling the global coronavirus pandemic. Here, we discuss factors involved in adenovirus cell binding, entry, and trafficking; how they influence efficiency of adenovirus-based vectors; and how they can be manipulated to enhance efficacy of genetically modified adenoviral variants. We focus particularly on endocytosis and how different adenovirus serotypes employ different endocytic pathways to gain cell entry, and thus, have different intracellular trafficking pathways that subsequently trigger different host antiviral responses.
Opposing protein pathways steer skin stem cells toward renewal or repair
Two proteins with opposing functions orchestrate the development and maintenance of healthy skin, Stanford Medicine researchers have found. Modulating their activity with topical drugs could reduce inflammation, aid wound healing and slow or halt the growth of skin cancer, the researchers believe. The findings are published in the journal Science.
The proteins are part of a family called ubiquitin-like proteins. Ubiquitination controls the targeted destruction and disposal of unneeded proteins in a cell. But in the skin, certain ubiquitin-like proteins instead switch on or off wide swaths of genes involved in cellular growth and development, the study found. In particular, they trigger progenitor (stem) cells in the lower layer of the skin to either mature and migrate to the skin surface or to self-renew.
“These two ubiquitin-like protein systems are remarkably dedicated and opposite in their functions,” said Paul Khavari, MD, Ph.D., chair of dermatology at the Stanford School of Medicine and senior author of the study. “One promotes the stem-cell state while the other drives differentiation. It’s like having two opposing forces that determine a cell’s fate.”
First 3D views of human cone opsins reveal how daylight vision reacts so fast
The retina of the human eye contains 6–7 million cone cells. These cells contain light-sensitive proteins known as cone opsins. They enable us to perceive our surroundings in detail in daylight. They allow us to see the world in thousands of colors: red strawberries, green leaves, the blue sky. They also enable us to see all the objects around us clearly. And they allow us to perceive fast movements, such as the rush of a train or the flight of a dragonfly.
Often, however, these all-rounders of daylight vision are also involved in retinal diseases. Impairment of cone receptor function, caused by genetic mutations or other degenerative processes, can lead to disorders such as color blindness and age-related macular degeneration (AMD), a disease affecting the central retina and causing progressive vision loss.
In a new study, Polina Isaikina and Sarah L. Schmidt, two researchers from the Center for Life Sciences at PSI, have succeeded for the first time in determining the three-dimensional structure of human cone opsins in their dark state and showing how their molecular architecture enables their rapid activation by light.
Teaching AI to Invent Enzymes Nature Never Imagined
Evolution is an extraordinary engine for enzymatic diversity, yet the chemistry it has explored remains a narrow slice of what DNA can encode. Deep generative models can design new proteins that bind ligands, but none have created enzymes without pre-specifying catalytic residues.
In this webinar, Chenghao Liu and Jarrid Brooks from the Arnold Lab at Caltech will introduce DISCO (DIffusion for Sequence-structure CO-design). This multimodal model co-designs protein sequence and 3D structure around arbitrary biomolecules, as well as inference-time scaling methods that optimize objectives across both modalities. Conditioned solely on reactive intermediates, DISCO designs diverse heme enzymes with novel active-site geometries. These enzymes catalyze new-to-nature carbene-transfer reactions, including alkene cyclopropanation, spirocyclopropanation, B-H, and C(sp^3)-H insertions, with high activities exceeding those of engineered enzymes. Random mutagenesis of a selected design further confirmed that enzyme activity can be improved through directed evolution. By providing a scalable route to evolvable enzymes, DISCO broadens the potential scope of genetically encodable transformations.
Is This the Key to Never Getting Old?
Awesome results and a new project to double mice lifespan. If I could fund one researcher right now it would be this man.
In this Conference talk, Dr. Greg Fahy presents stunning data from the TRIIM and TRIIM-X trials. His team has successfully regrown the human thymus in older adults, reversed epigenetic aging clocks by up to two years, and restored immune function to levels seen decades earlier.
Beyond the lab results, participants showed dramatic real-world improvements: 15% stronger muscles, 21% better VO2 max, and frailty scores dropping to near zero. Dr. Fahy also unveils the \.
Sugar-coated nanoparticles show promise for treating most aggressive form of brain cancer
Researchers at Oregon State University have potentially found a new way to treat the most aggressive form of brain cancer, glioblastoma, whose two-year survival rate is less than 30%.
The study, led by Oleh Taratula, Olena Taratula and Yoon Tae Goo of the OSU College of Pharmacy, addresses what they describe as the two most persistent obstacles to effective glioblastoma treatment: delivering therapeutic agents through the blood-brain barrier, the cell network that acts as a security checkpoint between the bloodstream and the central nervous system, and then getting those agents to preferentially target tumors.
In research published in the Journal of Controlled Release, the scientists demonstrate the novel treatment technique in a mouse model. They loaded lipid nanoparticles with genetic material that promotes tumor suppression, then coated the nanoparticles with a type of sugar. The result was a 50% median increase in glioblastoma survival time.
New effort will get genome sequences for entire Endangered Species list
The US Endangered Species Act compels the government to identify species at risk of extinction and devise plans to restore populations and the habitats they depend on. It has seen some spectacular successes, such as the restoration of the bald eagle to much of its original range. But over 2,300 plant and animal populations remain on the list, requiring ongoing government intervention.
On Thursday, it was announced that all of those species would see their genomes sequenced and tissue samples preserved to aid future conservation efforts. The work will be done by a partnership between two unexpected parties. One is the US government, which has generally attempted to undercut the Endangered Species Act as part of its anti-regulatory efforts. It is joined by Colossal Biosciences, a biotech company that has a controversial take on what actually constitutes a species.
Colossal has always said it had a conservation focus, but its headline-grabbing efforts have been directed toward restoring species that have been driven to extinction. It intends to do that by developing a combination of gene editing and reproductive technologies that it expects it can profitably license. But its dire wolf announcement, in which only a tiny handful of genetic changes were edited in to grey wolves, have raised some questions about its seriousness regarding these efforts.