Lifeboat Foundation: Safeguarding Humanity
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Category: genetics – Page 269

As the middle child of the “DNA to RNA to protein” central dogma, RNA didn’t get much press until its Covid-19 vaccine contribution. But the molecule is a double hero: it both carries genetic information, and—depending on its structure—can catalyze biological functions, regulate which genes are turned on, tweak your immune system, and even crazier, potentially pass down “memories” through generations.

It’s also frustratingly difficult to understand.

Similar to proteins, RNA also folds into complicated 3D structures. The difference, explain Drs. Rhiju Das and Ron Dror at Stanford University, is that we comparatively know so little about these molecules. There are 30 times as many types of RNA as there are proteins, but the number of deciphered RNA structures is less than one percent compared to proteins.

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In 2,001 Celera Genomics and the International Human Genome Sequencing Consortium published their initial drafts of the human genome, which revolutionized the field of genomics. While these drafts and the updates that followed effectively covered the euchromatic fraction of the genome, the heterochromatin and many other complex regions were left unfinished or erroneous. Addressing this remaining 8% of the genome, the Telomere-to-Telomere (T2T) Consortium has finished the first truly complete 3.055 billion base pair (bp) sequence of a human genome, representing the largest improvement to the human reference genome since its initial release. The new T2T-CHM13 reference includes gapless assemblies for all 22 autosomes plus Chromosome X, corrects numerous errors, and introduces nearly 200 million bp of novel sequence containing 2,226 paralogous gene copies, 115 of which are predicted to be protein coding. The newly completed regions include all centromeric satellite arrays and the short arms of all five acrocentric chromosomes, unlocking these complex regions of the genome to variational and functional studies for the first time.

The latest major update to the human reference genome was released by the Genome Reference Consortium (GRC) in2013and most recently patched in2019(GRCh38.p13). This assembly traces its origin to the publicly funded Human Genome Project and has been continually improved over the past two decades. Unlike the competing Celera assembly , and most modern genome projects that are also based on shotgun sequence assembly , the GRC human reference assembly is primarily based on Sanger sequencing data derived from bacterial artificial chromosome (BAC) clones that were ordered and oriented along the genome via radiation hybrid, genetic linkage, and fingerprint maps. This laborious approach resulted in what remains one of the most continuous and accurate reference genomes today. However, reliance on these technologies limited the assembly to only the euchromatic regions of the genome that could be reliably cloned into BACs, mapped, and assembled.

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A team of scientists found an unusual trick for growing bigger, heartier crops: inserting a human gene related to obesity and fat mass into plants to supersize their harvest.

Augmenting potatoes with the human gene that encodes a fat-regulating protein called FTO, which essentially alters the genetic code to rapidly mass-produce proteins, made otherwise identical potato plants grow crops that were 50 percent larger, Smithsonian Magazine reports. By growing more food without taking up more space for agriculture, the scientists say their work could help fight global hunger — without adding to its climate impact.

“It [was] really a bold and bizarre idea,” University of Chicago chemist Chuan He, coauthor of a paper published in Nature Biotechnology, told Smithsonian. “To be honest, we were probably expecting some catastrophic effects.”

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Nad plus works for alzheimers.

In June of 2,018 the World Health Organization (WHO) released the 11th edition of its International Classification of Diseases, and for the first time added aging. The classification of aging as a disease paves the way for new research into novel therapeutics to delay or reverse age-related illnesses such as cancer, cardiovascular and metabolic disease, and neurodegeneration., Nutrient sensing systems have been an intense focus of investigation, including mTOR (the mammalian target of rapamycin) for regulating protein synthesis and cell growth; AMPK (activated protein kinase) for sensing low energy states; and sirtuins, a family of seven proteins critical to DNA expression and aging, which can only function in conjunction with NAD+ (nicotinamide adenine dinucleotide), a coenzyme present in all living cells.

Across the kingdom of life, an increase in intracellular levels of NAD+ triggers shifts that enhance survival, including boosting energy production and upregulating cellular repair. In fact, the slow, ineluctable process of aging has been described as a “cascade of robustness breakdown triggered by a decrease in systemic NAD+ biosynthesis and the resultant functional defects in susceptible organs and tissues.” Aging is marked by epigenetic shifts, genomic instability, altered nutrient sensing ability, telomere attrition, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and dysregulated intercellular communication.,

By middle age, our NAD+ levels have plummeted to half that of our youth. Numerous studies have demonstrated that boosting NAD+ levels increases insulin sensitivity, reverses mitochondrial dysfunction, and extends lifespan., NAD+ levels can be increased by activating enzymes that stimulate synthesis of NAD+, by inhibiting an enzyme (CD38) that degrades NAD+, and by supplementing with NAD precursors, including nicotinamide riboside(NR) and nicotinamide mononucleotide (NMN)., A conceptual framework called NAD World, formulated over the last decade by developmental biologist Shin-ichiro Imai, MD, PhD, of Washington University School of Medicine, posits NMN as a critical, systemic signaling molecule that maintains biological robustness of the communication network supporting NAD+..

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Mutations are a part of life. Every time a virus replicates, there is a chance that its genetic code won’t be copied accurately. These typos travel inside new virus particles as they leave one body and move on to infect the next. Some of these mutations die out; others survive and circulate widely. Some mutations are harmless; others increase infectivity or allow a virus to better escape the immune system—that’s when public health bodies might deem that strain a variant of concern.

Swaps or deletions of single amino acids can change the shapes of different proteins. Mutations can happen in any of the proteins of SARS-CoV-2, and these may change the virus’s properties. Many of the worrisome mutations are found on the spike protein, as it is the target of antibody treatments and is mimicked by the currently authorized COVID-19 vaccines. Researchers are especially troubled when typos occur in two parts of the spike protein—the N-terminal domain, which is at the beginning of the protein and which some antibodies target, and the receptor-binding domain (RBD), which grabs hold of ACE2 receptors on human cells and starts the process of infection.

To understand how specific mutations affect the structure and function of the spike protein and what those changes mean for treatments and vaccines, C&EN talked to Priyamvada Acharya, Rory Henderson, and Sophie Gobeil at Duke University. With colleagues, these researchers have combined biochemical assays, cryo-electron microscopy, and modeling to show how the mutations seen in the variants of concern work together to change the stability of the spike protein. The spike is a trimer of three identical protein strands folded and interwoven together. Before the virus has infected a cell, the spike takes on two conformations: a down state, in which the RBD is hidden, and an up state, in which the RBD faces out, ready to bind to ACE2. The team found that different mutations can increase binding in different ways. This process, in which similar features are arrived at independently, is called convergent evolution.

SARS-CoV-2 variants are emerging and gaining traction around the world. What does that mean for our vaccines and treatments for COVID-19?

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Are there vertebrates occupying the planet today whose lifespans extend back to before the founding of the United States? Based on recent research, it seems very likely — and they exist in the form of sharks whose fermented meat are used in a very distinctive Icelandic dish. Scientists have found evidence that Greenland sharks live for hundreds of years — and that there are some whose lifespans extend to 400 or even 500 years.

For some scientists, the lengthy lifespans of certain creatures can also have an impact on research into making humans live longer. That’s true for the immortal jellyfish, and it also applies to the Greenland shark. A recent article by Jonathan Moens at Atlas Obscura explores what scientists have learned from their studies of the long-lived sharks — and what it might mean for humanity.

Greenland sharks’ longevity could be chalked up to genetic or lifestyle factors, or some combination of the two. The University of Manchester’s Holly Shiels suggested that, as Moens writes, “Greenland sharks may have a uniquely sophisticated system to repair damaged DNA.” Other scientists point to the sharks’ habitat — cold Arctic waters — and their ability to live for a long period of time on a relatively small amount of food as signs of a very efficient metabolism.

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Proteins can communicate through DNA, conducting a long-distance dialogue that serves as a kind of genetic “switch,” according to Weizmann Institute of Science researchers. They found that the binding of proteins to one site of a DNA molecule can physically affect another binding site at a distant location, and that this “peer effect” activates certain genes. This effect had previously been observed in artificial systems, but the Weizmann study is the first to show it takes place in the DNA of living organisms.

A team headed by Dr. Hagen Hofmann of the Chemical and Structural Biology Department made this discovery while studying a peculiar phenomenon in the soil bacteria Bacillus subtilis. A small minority of these bacteria demonstrate a unique skill: an ability to enrich their genomes by taking up bacterial gene segments scattered in the soil around them. This ability depends on a protein called ComK, a transcription factor, which binds to the DNA to activate the genes that make the scavenging possible. However, it was unknown how exactly this activation works.

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Because the brain responses in children with different forms of autism overlapped, future therapies that are effective for Phelan-McDermid syndrome could potentially help other autistic children with similar neural patterns, Siper says.

Brain responses to visual stimuli are smaller and weaker in children with Phelan-McDermid syndrome, an autism-linked genetic condition, than in non-autistic children, according to a new study. The difference in response is greater in children with larger genetic mutations.

Mutations or deletions in SHANK3, one of the genes most strongly linked to autism, cause Phelan-McDermid syndrome. More than 80 percent of people with the condition have autism; they also often have intellectual disability, developmental delays and other medical issues, though these traits and their severity can vary widely.

The new study is the first to use electroencephalography (EEG) to measure visual evoked potentials — brain responses that occur shortly after a person views a visual stimulus — in people with Phelan-McDermid syndrome. The team previously identified differences in these responses in people with ‘idiopathic’ autism, or autism with no known genetic cause. Other researchers have linked atypical visual evoked potentials to other single-gene causes of autism, such as Rett syndrome.

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The human body can be genetically inclined to attack its own cells, destroying the beta cells in the pancreas that make insulin, which helps convert sugar into energy. Called Type 1 diabetes, this disorder can occur at any age and can be fatal if not carefully managed with insulin shots or an insulin pump to balance the body’s sugar levels.

But there may be another, personalized option on the horizon, according to Xiaojun “Lance” Lian, associate professor of biomedical engineering and biology at Penn State. For the first time, Lian and his team converted human embryonic stem cells into beta cells capable of producing insulin using only small molecules in the laboratory, making the process more efficient and cost-effective.

Stem cells can become other cell types through signals in their environment, and some mature cells can revert to stem cells—induced pluripotency. The researchers found that their approach worked for human embryonic and induced pluripotent stem cells, both derived from federally approved stem cell lines. According to Lian, the effectiveness of their approach could reduce or eliminate the need for human embryonic stem cells in future work. They published their results today (Aug. 26) in Stem Cell Reports.

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