Lifeboat Foundation: Safeguarding Humanity
Toggle light / dark theme

Blog

Category: biotech/medical

Genome-embedded ribonucleotides arrest replicative DNA polymerases (Pols) and cause DNA breaks. Whether mammalian DNA repair Pols efficiently use template ribonucleotides and promote RNA-templated DNA repair synthesis remains unknown. We find that human Polθ reverse transcribes RNA, similar to retroviral reverse transcriptases (RTs). Polθ exhibits a significantly higher velocity and fidelity of deoxyribonucleotide incorporation on RNA versus DNA. The 3.2-Å crystal structure of Polθ on a DNA/RNA primer-template with bound deoxyribonucleotide reveals that the enzyme undergoes a major structural transformation within the thumb subdomain to accommodate A-form DNA/RNA and forms multiple hydrogen bonds with template ribose 2′-hydroxyl groups like retroviral RTs. Last, we find that Polθ promotes RNA-templated DNA repair in mammalian cells. These findings suggest that Polθ was selected to accommodate template ribonucleotides during DNA repair.

Polymerase θ (Polθ) is a unique DNA polymerase-helicase fusion protein in higher eukaryotes whose A-family polymerase domain evolved from Pol I enzymes (Fig. 1A) (1, 2). However, contrary to most Pol I enzymes, Polθ is highly error-prone and promiscuous (3–6), performs translesion synthesis (TLS) opposite DNA lesions (3, 7, 8), and facilitates microhomology-mediated end-joining (MMEJ) of double-strand breaks (DSBs) by extending partially base-paired 3′ single-stranded DNA (ssDNA) overhangs at DSB repair junctions (5, 9–12). Polθ is not expressed in most tissues but is highly expressed in many cancer cells, which corresponds to a poor clinical outcome (13, 14). Furthermore, Polθ confers resistance to genotoxic cancer therapies and promotes the survival of cells deficient in DNA damage response pathways (11, 13–16). Thus, Polθ represents a promising cancer drug target.

Intriguingly, Polθ has an inactive proofreading domain due to acquired mutations (Fig. 1A) (2). Inactivating the 3′-5′ proofreading function of closely related A-family bacterial Pol I Klenow fragment (KF) enables this polymerase to reverse transcribe RNA like retroviral reverse transcriptases (RTs), which lack proofreading activity (fig. S1A) (17, 18). Because Polθ is highly error-prone and promiscuous and contains an inactive proofreading domain, we hypothesized that it has RNA-dependent DNA synthesis activity. Given that ribonucleotides are the most frequently occurring nucleotide lesion in genomic DNA that arrest replicative Pols and cause DNA breaks (19, 20), we also envisaged that Polθ would tolerate template ribonucleotides during its DNA repair activities and thus promote RNA-templated DNA repair synthesis (RNA-DNA repair). Although RNA-DNA repair mechanisms have been demonstrated in genetically engineered yeast cells (21, 22), they remain obscure in mammalian cells.

Read more | >

Saccharine, aspartame, sucralose.

New research has discovered that common artificial sweeteners can cause previously healthy gut bacteria to become diseased and invade the gut wall, potentially leading to serious health issues.

The study, published in the International Journal of Molecular Sciences, is the first to show the of some of the most widely used artificial sweeteners—saccharin, sucralose, and aspartame—on two types of gut bacteria, E. coli (Escherichia coli) and E. faecalis (Enterococcus faecalis).

Previous studies have shown that artificial sweeteners can change the number and type of bacteria in the gut, but this new molecular research, led by academics from Anglia Ruskin University (ARU), has demonstrated that sweeteners can also make the bacteria pathogenic. It found that these can attach themselves to, invade, and kill Caco-2 cells, which are that line the wall of the intestine.

Read more | >

“We’re excited to share that AWS has acquired Wickr, an innovative company that has developed the industry’s most secure, end-to-end encrypted, communication technology,” Stephen Schmidt, Amazon Web Services’ vice president, wrote. With a nod to the company’s ever-deepening relationships with the military, and Washington in general, Schmidt added that Wickr’s features give “security conscious enterprises and government agencies the ability to implement important governance and security controls to help them meet their compliance requirements.” Schmidt himself has a background in this space: his LinkedIn profile notes he spent a decade at the FBI.

Wickr’s app — like secure messaging competitor Signal — has been popular with journalists and whistleblowers; it’s also been a go-to for criminals, Motherboard notes. It’s unclear if the proximity to the tech monolith will impact the app’s popularity for free users.

In Amazon’s case, Schmidt indicates the acquisition was at least partially influenced by the need to preserve information security while working remotely. “With the move to hybrid work environments, due in part to the COVID-19 pandemic, enterprises and government agencies have a growing desire to protect their communications,” he wrote.

Read more | >

STANFORD, Calif. — A groundbreaking “superhero” vaccine inspired by the DNA code of Olympic athletes could help transform society over the next decade, a top genetic scientist claims.

The vaccine would provide lifelong protection against three of the top ten leading causes of death, according to Euan Ashley, professor of medicine and genetics at Stanford University. The so-called “superhero” jab could offer simultaneous, long-term protection against heart disease, stroke, Alzheimer’s disease, and liver disease, thanks to advances in genetic engineering.

This breakthrough treatment would deliver the blueprint of “ideal” cells from men and women whose genes are more disease-resistant than those of the average person, together with an “instruction manual” to help the body “repair, tweak and improve” its own versions. A single dose could lead to a “body-wide genetic upgrade” that would cut the risk of premature death in some adults by as much as 50 percent.

Read more | >

“At first, we had a hard time believing the results. Many of these genes are classical hallmarks of aging and yet our results suggested that their activity is more a function of the presence of bacteria rather than the aging process,” said Dr. Shukla.

Notably, this included genes that control stress and immunity. The researchers tested the impact that the antibiotics had on these genes by starving some flies or infecting others with harmful bacteria and found no clear trend. At some ages, the antibiotics helped flies survive starvation or infection longer than normal whereas at other ages the drugs either had no effect or reduced the chances of survival.

NIH scientists discover that bacteria may drive activity of many hallmark aging genes in flies.

Read more | >

A simple blood test that can detect more than 50 types of cancer before any clinical signs or symptoms of the disease is accurate enough to be rolled out as a multi-cancer screening test, according to scientists.… See More.

The test is based on a type of DNA that is shed by tumours into the bloodstream.

Read more | >

I am waiting for tricorders.

The idea of visiting the doctor’s office with symptoms of an illness and leaving with a scientifically confirmed diagnosis is much closer to reality because of new technology developed by researchers at McMaster University.

Engineering, biochemistry and medical researchers from across campus have combined their skills to create a hand-held rapid test for bacterial infections that can produce accurate, reliable results in less than an hour, eliminating the need to send samples to a lab.

Their proof-of-concept research, published today in the journal Nature Chemistry, specifically describes the test’s effectiveness in diagnosing urinary tract infections from real clinical samples. The researchers are adapting the test to detect other forms of bacteria and for the rapid diagnosis of viruses, including COVID-19. They also plan to test its viability for detecting markers of cancer.

Read more | >

Circa 2015 In theory this big bang laser could eventually create complex matter but would need to be pocket-size as I want it on a smartphone to make a replicator so I can make fruit or food in space 😀

The Institute of Laser Engineering (ILE), Osaka University, has succeeded to reinforce the Petawatt laser “LFEX” to deliver up to 2000 trillion watts in the duration of one trillionth of one second (this corresponds to 1000 times the integrated electric power consumed in the world). By using this high-power laser, it is now possible to generate all of the high-energy quantum beams (electrons, ions, gamma ray, neutron, positron). Owing to such quantum beams with large current, we can make a big step forward not only for creating new fundamental technologies such as medical applications and non-destructive inspection of social infrastructures to contribute to our future life of longevity, safety, and security, but also for realization of laser fusion energy triggered by fast ignition.

Background and output of research

Petawatt lasers are used for study of basic science, generating such high-energy quantum beams as neutrons and ions, but only a few facilities in the world have Petawatt laser. So far, Petawatt lasers in the world have had relatively a small output (to a few tens of joules). ILE has achieved the world’s largest laser output of dozens of times those at other world-class lasers facilities (1000 joules or more).

Read more | >

In a study in Nature Plants, Yiping Qi, associate professor of Plant Science at the University of Maryland (UMD), introduces a new and improved CRISPR 3.0 system in plants, focusing on gene activation instead of traditional gene editing. This third generation CRISPR system focuses on multiplexed gene activation, meaning that it can boost the function of multiple genes simultaneously. According to the researchers, this system boasts four to six times the activation capacity of current state-of-the-art CRISPR technology, demonstrating high accuracy and efficiency in up to seven genes at once. While CRISPR is more often known for its gene editing capabilities that can knock out genes that are undesirable, activating genes to gain functionality is essential to creating better plants and crops for the future.

“While my lab has produced systems for simultaneous gene editing [multiplexed editing] before, editing is mostly about generating loss of function to improve the crop,” explains Qi. “But if you think about it, that strategy is finite, because there aren’t endless genes that you can turn off and actually still gain something valuable. Logically, it is a very limited way to engineer and breed better traits, whereas the plant may have already evolved to have different pathways, defense mechanisms, and traits that just need a boost. Through activation, you can really uplift pathways or enhance existing capacity, even achieve a novel function. Instead of shutting things down, you can take advantage of the functionality already there in the genome and enhance what you know is useful.”

In his new paper, Qi and his team validated the CRISPR 3.0 system in rice, tomatoes, and Arabidopsis (the most popular model plant species, commonly known as rockcress). The team showed that it is possible to simultaneously activate many kinds of genes, including faster flowering to speed up the breeding process. But this is just one of the many advantages of multiplexed activation, says Qi.

Read more | >