StackWarp is a hardware flaw affecting AMD Zen 1–5 CPUs that allows privileged hosts to execute code inside SEV-SNP confidential virtual machines.
Category: computing – Page 4
Systematic identification of single transcription factor perturbations that drive cellular and tissue rejuvenation
Significance.
Cellular rejuvenation through transcriptional reprogramming has emerged as exciting approach to counter aging. However, to date, only a few of rejuvenating transcription factor (TF) perturbations have been identified. In this work, we developed a discovery platform to systematically identify single TF perturbations that drive cellular and tissue rejuvenation. Using a classical model of human fibroblast aging, we identified more than a dozen candidate TF perturbations and validated four of them (E2F3, EZH2, STAT3, ZFX) through cellular/molecular phenotyping. At the tissue level, we demonstrate that overexpression of EZH2 alone is sufficient to rejuvenate the liver in aged mice, significantly reducing fibrosis and steatosis, and improving glucose tolerance. Our work expanded the list of candidate rejuvenating TFs for future translation. Abstract.
Cellular rejuvenation through transcriptional reprogramming is an exciting approach to counter aging. Using a fibroblast-based model of human cell aging and Perturb-seq screening, we developed a systematic approach to identify single transcription factor (TF) perturbations that promote rejuvenation without dedifferentiation. Overexpressing E2F3 or EZH2, and repressing STAT3 or ZFX, reversed cellular hallmarks of aging—increasing proliferation, proteostasis, and mitochondrial activity, while decreasing senescence. EZH2 overexpression in vivo rejuvenated livers in aged mice, reversing aging-associated gene expression profiles, decreasing steatosis and fibrosis, and improving glucose tolerance. Mechanistically, single TF perturbations led to convergent downstream transcriptional programs conserved in different aging and rejuvenation models. These results suggest a shared set of molecular requirements for cellular and tissue rejuvenation across species. Sign up for PNAS alerts.
Get alerts for new articles, or get an alert when an article is cited. Cellular rejuvenation through transcriptional reprogramming is an exciting approach to counter aging and bring cells back to a healthy state. In both cell and animal aging models, there has been significant recent progress in rejuvenation research. Systemic factors identified in young blood through models such as heterochronic parabiosis (in which the circulatory systems of a young and aged animal are joined) rejuvenate various peripheral tissues and cognitive function in the brain (1–4). Partial reprogramming at the cellular level with the Yamanaka factors (four stem cell transcription factors) reverses cellular and tissue-level aging markers and can extend lifespan in old mice (5–8). These discoveries support the notion that transcriptional reprogramming is a powerful approach to improving the health of cells and tissues, and one day could be used as an approach for human therapeutics. However, to date, only a couple of rejuvenating transcription factor (TF) perturbations have been identified (9, 10) and most of them require the overexpression of TFs. We hypothesized that there are multiple other TF perturbations which could reset cells and tissues back to a healthier or younger state—rejuvenating them. Identifying complementary rejuvenating strategies is important as it will increase the chance of successful future translation. We developed a high-throughput platform, the Transcriptional Rejuvenation Discovery Platform (TRDP), which combines computational analysis of TF binding motifs and target predictions (Materials and Methods), global gene expression data of old and young cell states, and experimental genetic perturbations to identify which TF can restore overall gene expression and cell phenotypes to a younger, healthier state. We developed TRDP to be applicable to any cell type, and in both aging and disease settings, with the only requirements being baseline comparison of gene expression data comparing the older/diseased state to the younger/healthier state and the ability to perform genetic perturbations. To model aging in vitro as a validation of our approach, we used the canonical aging model of passaged fibroblasts (11, 12). We tested 400 TF perturbations via our screen and validated reversal of key cellular aging hallmarks in late passage human fibroblasts for four top TFs: E2F3, EZH2, STAT3, and ZFX. Moreover, EZH2 overexpression in vivo rejuvenated livers in aged mice—reversing aging-associated global gene expression profiles, significantly reducing steatosis and fibrosis, and improving glucose tolerance. These findings point to a conserved set of molecular requirements for cellular and tissue rejuvenation.
Soft organic electrochemical neurons operating at biological speed
Organic electrochemical neurons respond to brain signals in real time, firing at biologically relevant speeds. Their flexibility and low power use could enable soft, implantable systems for closed-loop neuromodulation and future brain–computer interfaces.
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Scientists uncover new quantum state that could power future technologies
Scientists have discovered a new quantum state of matter that connects two significant areas of physics, potentially leading to advancements in computing, sensing and materials science.
A study published in Nature Physics, co-led by Rice University’s Qimiao Si, brings together quantum criticality, where electrons fluctuate between different phases, and electronic topology, which describes a form of quantum organization based on the wave behavior of electrons.
The researchers found that strong interactions among electrons can produce topological behavior, paving the way for new technologies that could use this quantum state in real-world applications.
Engineers just created a “phonon laser” that could shrink your next smartphone
Engineers have created a device that generates incredibly tiny, earthquake-like vibrations on a microchip—and it could transform future electronics. Using a new kind of “phonon laser,” the team can produce ultra-fast surface waves that already play a hidden role in smartphones, GPS systems, and wireless tech. Unlike today’s bulky setups, this single-chip device could deliver far higher performance using less power, opening the door to smaller, faster, and more efficient phones and wireless devices.
This Quantum Discovery May Bypass the ‘No-Cloning Theorem,’ Opening the Door to Quantum Cloud Storage
Scientists have demonstrated a new method that could allow quantum information to be safely backed up, overcoming one of the longest-standing limitations in quantum computing without violating the fundamental laws that govern quantum systems.
The research describes a way to encode the information contained in a qubit across multiple entangled systems, allowing the original quantum state to be recovered later without directly copying it.
New map reveals a rugged world beneath the Antarctic ice sheet
Scientists have discovered there is more to Antarctica than meets the eye. A new map of the landscape beneath the frozen continent’s ice sheet has revealed a previously hidden world of mountains, deep canyons and rugged hills in unprecedented detail.
The Antarctic ice sheet is a vast expanse of ice covering approximately 98% of the continent. While the frozen surface has been fairly well-studied, the ground beneath this two-kilometer-thick layer has remained a mystery. In fact, until now, we knew more about the surface of Mars than what lies beneath the bottom of our own planet.
The ice sheet plays a crucial role in our climate. Not only is it a major freshwater reservoir, but its icy surface reflects sunlight, helping cool Earth. But because our computer models are missing key details about the land it sits on, it is difficult to predict factors such as exactly how fast the ice will melt and how much sea levels will rise.
Rocks and rolls: The computational infrastructure of earthquakes and physics of planetary science
Sometimes to truly study something up close, you have to take a step back. That’s what Andrea Donnellan does. An expert in Earth sciences and seismology, she gets much of her data from a bird’s-eye view, studying the planet’s surface from the air and space, using the data to make discoveries and deepen understanding about earthquakes and other geological processes.
“The history of Earth processes is written in the landscapes,” Donnellan said. “Studying Earth’s surface can help us understand what is happening now and what might happen in the future.”
Donnellan, professor and head of the Department of Earth, Atmospheric, and Planetary Sciences in Purdue’s College of Science, has watched Earth for a long time. Her original research was studying and tracking glaciers in Antarctica.