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Category: genetics – Page 237

DARPA Wants to Develop a Drug to Make People Resistant to Extreme Cold

Last week, Rice University in Houston announced that one of its assistant professors of bioengineering, Jerzy Szablowski, received a Young Faculty Award from DARPA to research non-genetic drugs that can “temporarily enhance the human body’s resilience to extreme cold exposure.”

Thermogenesis is the use of energy to create heat, and our bodies have two different ways of doing this. One is shivering, which we’re all familiar with. The other, which Szablowski simply calls non-shivering thermogenesis, involves burning off brown adipose tissue (BAT), or brow n fat.

This type of fat exists specifically to warm us up when we get cold; it stores energy and only activates in cold temperatures. Most of our body fat is white fat. It builds up when we ingest more calories than we burn and stores those calories for when we don’t get enough energy from food. An unfortunate majority of American adults have the opposite problem: too much white fat, which increases the risk of conditions like heart disease and Type 2 diabetes.

Cellular Reprogramming Extends Lifespan in Mice, Longevity Startup Says

Cellular reprogramming builds on the Nobel Prize-winning work of Shinya Yamanaka, who showed that adult cells could be transformed back into stem cells by exposing them to a specific set of genome-regulating proteins known as transcription factors. The Salk team’s innovation was to reduce the exposure times to the so-called Yamanaka factors, which they found could reverse epigenetic changes to the cells without reverting them to stem cells.

While the approach led to clear increases in lifespan in prematurely aging mice, the fact that no one had been able to replicate the result in healthy mice since then raised doubts about the approach. “Different groups have tried this experiment, and the data have not been positive so far,” Alejandro Ocampo, from the University of Lausanne in Switzerland, who carried out the original Salk experiments, told MIT Technology Review.

But now, Rejuvenate Bio claims that when they exposed healthy mice near the end of their lives to a subset of the Yamanaka factors, they lived for another 18 weeks on average, compared to just 9 weeks for those that didn’t undergo cellular reprogramming.

Gene Therapy Mediated Partial Reprogramming Extends Lifespan and Reverses Age-Related Changes in Aged Mice

Aging is a complex process best characterized as the chronic dysregulation of cellular processes leading to deteriorated tissue and organ function. While aging cannot currently be prevented, its impact on lifespan and healthspan in the elderly can potentially be minimized by interventions that aim to return these cellular processes to optimal function. Recent studies have demonstrated that partial reprogramming using the Yamanaka factors (or a subset; OCT4, SOX2, and KLF4; OSK) can reverse age-related changes in vitro and in vivo. However, it is still unknown whether the Yamanaka factors (or a subset) are capable of extending the lifespan of aged wild type mice. Here, we show that systemically delivered AAVs, encoding an inducible OSK system, in 124-week-old mice extends the median remaining lifespan by 109% over wild-type controls and enhances several health parameters. Importantly, we observed a significant improvement in frailty scores indicating that we were able to improve the healthspan along with increasing the lifespan. Furthermore, in human keratinocytes expressing exogenous OSK, we observed significant epigenetic markers of age-reversal, suggesting a potential reregulation of genetic networks to a younger, potentially healthier state. Together, these results may have important implications for the development of partial reprogramming interventions to reverse age-associated diseases in the elderly.

All authors performed the work while employed at Rejuvenate Bio Inc. Rejuvenate Bio is a therapeutics company translating gene therapies to treat age-related diseases.

Resurrecting the Dead (Molecules)

Year 2017 face_with_colon_three

Biological molecules, like organisms themselves, are subject to genetic drift and may even become “extinct”. Molecules that are no longer extant in living systems are of high interest for several reasons including insight into how existing life forms evolved and the possibility that they may have new and useful properties no longer available in currently functioning molecules. Predicting the sequence/structure of such molecules and synthesizing them so that their properties can be tested is the basis of “molecular resurrection” and may lead not only to a deeper understanding of evolution, but also to the production of artificial proteins with novel properties and even to insight into how life itself began.

UK Meteorite That Fell To Earth Contains Building Blocks For Life

Basically many have theorized that these seeds coming from meteorites mean that essentially perhaps that life started from seeds like this. Going much deeper down the rabbit hole we actually are starting to see a grand design possibly by actually organisms that evolved into what we have now over millions of years which is actually weird because all earth would have been just a rock but this could be a grand architecture genetically even from the first seed to the biological singularity. This could Basically prove the existence of some entity that may have created humans and all life most like from this seed which means whether it is alien gods or God there will be so much more discover due to this complexity which can benefit all medicine and also genetic engineering 🤔 😉 😀

The fact the first of four surviving pieces was collected within 12 hours of landing, allowing little time for contamination, added to the meteorite’s value. Indeed, because the abundance of organic material in the meteorite was ten times lower than in other carbonaceous chondrites, they might not have been distinguishable from Earthly contamination had it not been retrieved so quickly. As it is, some of the amino acids found are quite rare on Earth, confirming their extraterrestrial origins.

The Winchcombe stones had a number of features never previously seen in meteorites, including low amino acid abundance for a carbonaceous chondrite but unusual ratios among the amino acids and PAHs that are present. Combined with the incomplete conversion of Winchcombe’s components into solid rock, this led the authors to speculate Winchcombe could represent a new class of meteorite that has not been studied before.

Perhaps in part because of its weak structure, very little of the Winchcombe meteorite made it to the ground. Just 600 grams (1.3 pounds) have been recovered, compared to a 27-kilogram (60-pound) carbonaceous chondrite that landed in Costa Rica in 2019. This prevented certain forms of analysis that require bulk samples.

Resting Heart Rate, Heart Rate Variability: What’s Optimal, 1600+ Days of Data

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New nanoparticles deliver therapy throughout the brain and edit Alzheimer’s gene in mice

Gene therapies have the potential to treat neurological disorders like Alzheimer’s and Parkinson’s diseases, but they face a common barrier—the blood-brain barrier. Now, researchers at the University of Wisconsin-Madison have developed a way to move therapies across the brain’s protective membrane to deliver brain-wide therapy with a range of biological medications and treatments.

“There is no cure yet for many devastating disorders,” says Shaoqin “Sarah” Gong, UW-Madison professor of ophthalmology and visual sciences and biomedical engineering and researcher at the Wisconsin Institute for Discovery. “Innovative brain-targeted delivery strategies may change that by enabling noninvasive, safe and efficient delivery of CRISPR genome editors that could, in turn, lead to genome-editing therapies for these diseases.”

CRISPR is a molecular toolkit for editing (for example, to correct mutations that may cause disease), but the toolkit is only useful if it can get through security to the job site. The is a membrane that selectively controls access to the brain, screening out toxins and pathogens that may be present in the bloodstream. Unfortunately, the bars some beneficial treatments, like certain vaccines and gene therapy packages, from reaching their targets because in lumps them in with hostile invaders.

Ten years and 1,000 studies later, epigeneticists discover problems in their arsenal

Twenty years ago, following the initial sequencing of the human genome, geneticists started carrying out extensive genome-wide association studies to find genomic regions connected to human disease.

In addition to the DNA sequence, another stable level of molecular data created during development called epigenetic modifications also plays a role in disease risk.

Researchers have been examining these epigenetic changes for more than ten years to look for links to disease. More than a thousand of these epigenome-wide association studies have been published as of late.

Scientists make new discovery about reversing the ageing process

Researchers look at DNA of lab mice and ultimately reverse ageing process Related: Empowered Aging Scientists have made a new discovery about how to reverse the ageing process through looking at the way in which cells in DNA are organised. In a new study published in Cell, David Sinclair, who is a professor of genetics at Harvard Medical School, and his team described how they looked at a genome, which is called epigenome, in mice to study the ageing process.

Conditional, tissue-specific CRISPR/Cas9 vector system in zebrafish reveal the role of neuropilin-1b in heart regeneration

CRISPR/Cas9 technology-mediated genome editing has significantly improved the targeted inactivation of genes in vitro and in vivo in many organisms. In this study, we have reported a novel CRISPR-based vector system for conditional tissue-specific gene ablation in zebrafish. Specifically, the cardiac-specific cardiac myosins light chain 2 (cmlc2) promoter drives Cas9 expression to silence the neuropilin-1(nrp1) gene in cardiomyocytes in a heat-shock inducible manner. This vector system establishes a unique tool to regulate the gene knockout in both the developmental and adult stages and hence, widens the possibility of loss-of-function studies in zebrafish at different stages of development and adulthood. Using this approach, we investigated the role of neuropilin isoforms nrp1a and nrp1b in response to cardiac injury and regeneration in adult zebrafish hearts. We observed that both the isoforms (nrp1a and nrp1b) are upregulated after the cryoinjury. Interestingly, the nrp1b-knockout significantly altered heart regeneration and impaired cardiac function in the adult zebrafish, demonstrated by reduced heart rate (ECG), ejection fractions, and fractional shortening. In addition, we show that the knockdown of nrp1b but not nrp1a induces activation of the cardiac remodeling genes in response to cryoinjury. To our knowledge, this is the first study where we have reported a heat shock-mediated conditional knockdown of nrp1a and nrp1b isoforms using CRISPR/Cas9 technology in the cardiomyocyte in zebrafish, and furthermore have identified a crucial role for nrp1b isoform in zebrafish cardiac remodeling and eventually heart function in response to injury.

The authors have declared no competing interest.

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