Transhumanismus

A New Treatment Rejuvenates Aging Immune Systems in Elderly Mice

Singularity HUB - 29 Březen, 2024 - 19:32

Our immune system is like a well-trained brigade.

Each unit has a unique specialty. Some cells directly kill invading foes; others release protein “markers” to attract immune cell types to a target. Together, they’re a formidable force that fights off biological threats—both pathogens from outside the body and cancer or senescent “zombie” cells from within.

With age, the camaraderie breaks down. Some units flare up, causing chronic inflammation that wreaks havoc in the brain and body. These cells increase the risk of dementia, heart disease, and gradually sap muscles. Other units that battle novel pathogens—such as a new strain of flu—slowly dwindle, making it harder to ward off infections.

All these cells come from a single source: a type of stem cell in bone marrow.

This week, in a study published in Nature, scientists say they restored the balance between the units in aged mice, reverting their immune systems back to a youthful state. Using an antibody, the team targeted a subpopulation of stem cells that eventually develops into the immune cells underlying chronic inflammation. The antibodies latched onto targets and rallied other immune cells to wipe them out.

In elderly mice, the one-shot treatment reinvigorated their immune systems. When challenged with a vaccine, the mice generated a stronger immune response than non-treated peers and readily fought off later viral infections.

Rejuvenating the immune system isn’t just about tackling pathogens. An aged immune system increases the risk of common age-related medical problems, such as dementia, stroke, and heart attacks.

“Eliminating the underlying drivers of aging is central to preventing several age-related diseases,” wrote stem cell scientists Drs. Yasar Arfat Kasu and Robert Signer at the University of California, San Diego, who were not involved in the study. The intervention “could thus have an outsized impact on enhancing immunity, reducing the incidence and severity of chronic inflammatory diseases and preventing blood disorders.”

Stem Cell Succession

All blood cells arise from a single source: hematopoietic stem cells, or blood stem cells, that reside in bone marrow.

Some of these stem cells eventually become “fighter” white blood cells, including killer T cells that—true to their name—directly destroy cancerous cells and infections. Others become B cells that pump out antibodies to tag invaders for elimination. This unit of the immune system is dubbed “adaptive” because it can tackle new intruders the body has never seen.

Still more blood stem cells transform into myriad other immune cell types—including those that literally eat their foes. These cells form the innate immune unit, which is present at birth and the first line of defense throughout our lifetime.

Unlike their adaptive comrades, which more precisely target invaders, the innate unit uses a “burn it all” strategy to fight off infections by increasing local inflammation. It’s a double-edged sword. While useful in youth, with age the unit becomes dominant, causing chronic inflammation that gradually damages the body.

The reason for this can be found in the immune system’s stem cell origins.

Blood stem cells come in multiple types. Some produce both immune units equally; others are biased towards the innate unit. With age, the latter gradually take over, increasing chronic inflammation while lowering protection against new pathogens. This is, in part, why elderly people are advised to get new flu shots, and why they were first in line for vaccination against Covid-19.

The new study describes a practical approach to rebalancing the aged immune system. Using an antibody-based therapy, the scientists directly obliterated the population of stem cells that lead to chronic inflammation.

Blood Bath

Like most cells, blood stem cells have a unique fingerprint—a set of proteins that dot their surfaces. A subset of the cells, dubbed my-HSCs, are more likely to produce cells in the innate immune system, which triggers chronic inflammation with age.

By mining multiple gene expression datasets from blood stem cells, the team found three protein markers they could use to identify and target my-HSCs cells in aged mice. They then engineered an antibody to target the cells for elimination.

Just a week after infusing it into elderly mice, the antibody had reduced the number of myHSC cells in their bone marrow without harming other blood stem cells. A genetic screen confirmed the mice’s immune profile was more like that of young mice.

The one-shot treatment lasted “strikingly” long, wrote Kasu and Signer. A single injection reduced the troublesome stem cells for at least two months—roughly a twelfth of a mouse’s lifespan. With my-HSCs no longer dominant, healthy blood stem cells gained ground inside the bone marrow. For at least four months, the treated mice produced more cells in the adaptive immune unit than their similarly aged peers, while having less overall inflammation.

As an ultimate test, the team challenged elderly mice with a difficult virus. To beat the infection, multiple components of the adaptive immune system had to rev up and work in concert.

Some elderly mice received a vaccine and the antibody treatment. Others only received the vaccine. Those treated with the antibody mounted a larger protective immune response. When given a dose of the virus, their immune systems rapidly recruited adaptive immune cells, and fought off the infection—whereas those receiving only the vaccine struggled.

Restoring Balance

The study shows that not all blood stem cells are alike. Eliminating those that cause inflammation directly changes the biological “age” of the entire immune system, allowing it to better tackle damaging changes in the body and fight off infections.

Like a leaking garbage can, innate immune cells can dump inflammatory molecules into their neighborhood. By cleaning up the source, the antibody could have also changed the environment the cells live in, so they are better able to thrive during aging.

Additionally, the immune system is an “eye in the sky” for monitoring cancer. Reviving immune function could restore the surveillance systems needed to eliminate cancer cells. The antibody treatment here could potentially tag-team with CAR T therapy or classic anti-cancer therapies, such as chemotherapy, as a one-two punch against the disease.

But it isn’t coming to clinics soon. Without unexpected setbacks or regulatory hiccups, the team estimates three to five years before testing in people. As a next step, they’re looking to expand the therapy to tackle other disorders related to a malfunctioning immune system.

Image Credit: Volker Brinkmann

Kategorie: Transhumanismus

These Plants Could Mine Valuable Metals From the Soil With Their Roots

Singularity HUB - 28 Březen, 2024 - 20:26

The renewable energy transition will require a huge amount of materials, and there are fears we may soon face shortages of some critical metals. US government researchers think we could rope in plants to mine for these metals with their roots.

Green technologies like solar power and electric vehicles are being adopted at an unprecedented rate, but this is also straining the supply chains that support them. One area of particular concern includes the metals required to build batteries, wind turbines, and other advanced electronics that are powering the energy transition.

We may not be able to sustain projected growth at current rates of production of many of these minerals, such as lithium, cobalt, and nickel. Some of these metals are also sourced from countries whose mining operations raise serious human rights or geopolitical concerns.

To diversify supplies, the government research agency ARPA-E is offering $10 million in funding to explore “phytomining,” in which certain species of plants are used to extract valuable metals from the soil through their roots. The project is focusing on nickel first, a critical battery metal, but in theory, it could be expanded to other minerals.

“In order to accomplish the goals laid out by President Biden to meet our clean energy targets, and support our economy and national security, it’s going to take [an] all-hands-on-deck approach and innovative solutions,” ARPA-E director Evelyn Wang said in a press release.

“By exploring phytomining to extract nickel as the first target critical material, ARPA-E aims to achieve a cost-competitive and low-carbon footprint extraction approach needed to support the energy transition.”

The concept of phytomining has been around for a while and relies on a class of plants known as “hyperaccumulators.” These species can absorb a large amount of metal through their roots and store it in their tissues. Phytomining involves growing these plants in soils with high levels of metals, harvesting and burning the plants, and then extracting the metals from the ash.

The ARPA-E project, known as Plant HYperaccumulators TO MIne Nickel-Enriched Soils (PHYTOMINES), is focusing on nickel because there are already many hyperaccumulators known to absorb the metal. But finding, or creating, species able to economically mine the metal in North America will still be a significant challenge.

One of the primary goals of the project is to optimize the amount of nickel these plants can take in. This could involve breeding or genetically modifying plants to enhance these traits or altering the microbiome of either the plants or the surrounding soil to boost absorption.

The agency also wants to gain a better understanding of the environmental and economic factors that could determine the viability of the approach, such as the impact of soil mineral composition, the land ownership status of promising sites, and the lifetime costs of a phytomining operation.

But while the idea is still at a nebulous stage, there is considerable potential.

“In soil that contains roughly 5 percent nickel—that is pretty contaminated—you’re going to get an ash that’s about 25 to 50 percent nickel after you burn it down,” Dave McNear, a biogeochemist at the University of Kentucky, told Wired.

“In comparison, where you mine it from the ground, from rock, that has about .02 percent nickel. So you are several orders of magnitude greater in enrichment, and it has far less impurities.”

Phytomining would also be much less environmentally damaging than traditional mining, and it could help remediate soil polluted with metals so they can be farmed more conventionally. While the focus is currently on nickel, the approach could be extended to other valuable metals too.

The main challenge will be finding a plant that is suitable for American climates that grows quickly. “The problem has historically been that they’re not often very productive plants,” Patrick Brown, a plant scientist at the University of California, Davis, told Wired. “And the challenge is you have to have high concentrations of nickel and high biomass to achieve a meaningful, economically viable outcome.”

Still, if researchers can square that circle, the approach could be a promising way to boost supplies of the critical minerals needed to support the transition to a greener economy.

Image Credit: Nickel hyperaccumulator Alyssum argenteum / David Stang via Wikimedia Commons

Kategorie: Transhumanismus

Now We Can See the Magnetic Maelstrom Around Our Galaxy’s Supermassive Black Hole

Singularity HUB - 28 Březen, 2024 - 00:10

Black holes are known for ferocious gravitational fields. Anything wandering too close, even light, will be swallowed up. But other forces may be at play too.

In 2021, astronomers used the Event Horizon Telescope (EHT) to make a polarized image of the enormous black hole at the center of the galaxy M87. The image showed an organized swirl of magnetic fields threading the matter orbiting the object. M87*, as the black hole is known, is nearly 1,000 times bigger than our own galaxy’s central black hole, Sagittarius A* (Sgr A*) and is dining on the equivalent of a few suns per year. With its comparatively modest size and appetite—Sgr A* is basically fasting at the moment—scientists wondered if our galaxy’s black hole would have strong magnetic fields too.

Now, we know.

In the first polarized image of Sgr A*, released alongside two papers published today (here and here), EHT scientists say the black hole has strong magnetic fields akin to those seen in M87*. The image depicts a fiery whirlpool (the disc of material falling into Sgr A*) circling the drain (the black hole’s shadow) with magnetic field lines woven throughout.

In contrast to unpolarized light, polarized light is oriented in only one direction. Like a pair of quality sunglasses, magnetized regions in space polarize light too. These polarized images of the two black holes therefore map out their magnetic fields.

And surprisingly, they’re similar.

Side-by-side polarized images of supermassive black holes M87* and Sagittarius A*. Image Credit: EHT Collaboration

“With a sample of two black holes—with very different masses and very different host galaxies—it’s important to determine what they agree and disagree on,” Mariafelicia De Laurentis, EHT deputy project scientist and professor at the University of Naples Federico II, said in a press release. “Since both are pointing us toward strong magnetic fields, it suggests that this may be a universal and perhaps fundamental feature of these kinds of systems.”

Making the image was no simple task. Compared to M87*, whose disc is larger and moves relatively slowly, imaging Sgr A* is like trying to photograph a cosmic toddler—its material is always in motion, reaching nearly the speed of light. The scientists had to use new tools in addition to those that yielded the polarized image of M87* and weren’t even sure the image would be possible.

Such technical feats take enormous teams of scientists organized across the globe. The first three pages of each new paper are dedicated to authors and affiliations. In addition, the EHT itself spans the world. Astronomers stitch observations made by eight telescopes into a virtual Earth-sized telescope capable of resolving objects the apparent size of a donut on the moon as viewed from the surface of our planet.

The EHT team plans to make more observations—the next round for Sgr A* begins next month—and add telescopes on Earth and space to increase the quality and breadth of the images. One outstanding question is whether Sgr A* has a jet of material shooting out from its poles like M87* does. The ability to make movies of the black hole later this decade—which should be spectacular—could resolve the mystery.

“We expect strong and ordered magnetic fields to be directly linked to the launching of jets as we observed for M87*,” Sara Issaoun, research co-leader and a fellow at Harvard & Smithsonian’s Center for Astrophysics, told Space.com. “Since Sgr A*, with no observed jet, seems to have a very similar geometry, perhaps there is also a jet lurking in Sgr A* waiting to be observed, which would be super exciting!”

The discovery of a jet, added to strong magnetic fields, would mean these features may be common to supermassive black holes across the spectrum. Learning more about their features and behavior can help scientists piece together a better picture of how galaxies, including the Milky Way, evolve over eons in tandem with the black holes at their hearts.

Image Credit: EHT Collaboration

Kategorie: Transhumanismus

Human Artificial Chromosomes Could Ferry Tons More DNA Cargo Into Cells

Singularity HUB - 26 Březen, 2024 - 22:48

The human genetic blueprint is deceptively simple. Our genes are tightly wound into 46 X-shaped structures called chromosomes. Crafted by evolution, they carry DNA and replicate when cells divide, ensuring the stability of our genome over generations.

In 1997, a study torpedoed evolution’s playbook. For the first time, a team created an artificial human chromosome using genetic engineering. When delivered into a human cell in a petri dish, the artificial chromosome behaved much like its natural counterparts. It replicated as cells divided, leading to human cells with 47 chromosomes.

Rest assured, the goal wasn’t to artificially evolve our species. Rather, artificial chromosomes can be used to carry large chunks of human genetic material or gene editing tools into cells. Compared to current delivery systems—virus carriers or nanoparticles—artificial chromosomes can incorporate far more synthetic DNA.

In theory, they could be designed to ferry therapeutic genes into people with genetic disorders or add protective ones against cancer.

Yet despite over two decades of research, the technology has yet to enter the mainstream. One challenge is that the short DNA segments linking up to form the chromosomes stick together once inside cells, making it difficult to predict how the genes will behave.

This month, a new study from the University of Pennsylvania changed the 25-year-old recipe and built a new generation of artificial chromosomes. Compared to their predecessors, the new chromosomes are easier to engineer and use longer DNA segments that don’t clump once inside cells. They’re also a large carrier, which in theory could shuttle genetic material roughly the size of the largest yeast chromosome into human cells.

“Essentially, we did a complete overhaul of the old approach to HAC [human artificial chromosome] design and delivery,” study author Dr. Ben Black said in a press release.

“The work is likely to reinvigorate efforts to engineer artificial chromosomes in both animals and plants,” wrote the University of Georgia’s Dr. R. Kelly Dawe, who was not involved in the study.

Shape of You

Since 1997, artificial genomes have become an established biotechnology. They’ve been used to rewrite DNA in bacteria, yeast, and plants, resulting in cells that can synthesize life-saving medications or eat plastic. They could also help scientists better understand the functions of the mysterious DNA sequences littered throughout our genome.

The technology also brought about the first synthetic organisms. In late 2023, scientists revealed yeast cells with half their genes replaced by artificial DNA—the team hopes to eventually customize every single chromosome. Earlier this year, another study reworked parts of a plant’s chromosome, further pushing the boundaries of synthetic organisms.

And by tinkering with the structures of chromosomes—for example, chopping off suspected useless regions—we can better understand how they normally function, potentially leading to treatments for diseases.

The goal of building human artificial chromosomes isn’t to engineer synthetic human cells. Rather, the work is meant to advance gene therapy. Current methods for carrying therapeutic genes or gene editing tools into cells rely on viruses or nanoparticles. But these carriers have limited cargo capacity.

If current delivery vehicles are like sailboats, artificial human chromosomes are like cargo ships, with the capacity to carry a far larger and wider range of genes.

The problem? They’re hard to build. Unlike bacteria or yeast chromosomes, which are circular in shape, our chromosomes are like an “X.” At the center of each is a protein hub called the centromere that allows the chromosome to separate and replicate when a cell divides.

In a way, the centromere is like a button that keeps fraying pieces of fabric—the arms of the chromosome—intact. Earlier efforts to build human artificial chromosomes focused on these structures, extracting DNA letters that could express proteins inside human cells to anchor the chromosomes. However, these DNA sequences rapidly grabbed onto themselves like double-sided tape, ending in balls that made it difficult for cells to access the added genes.

One reason could be that the synthetic DNA sequences were too short, making the mini-chromosome components unreliable. The new study tested the idea by engineering a far larger human chromosome assembly than before.

Eight Is the Lucky Number

Rather than an X-shaped chromosome, the team designed their human artificial chromosome as a circle, which is compatible with replication in yeast. The circle packed a hefty 760,000 DNA letter pairs—roughly 1/200 the size of an entire human chromosome.

Inside the circle were genetic instructions to make a sturdier centromere—the “button” that keeps the chromosome structure intact and can make it replicate. Once expressed inside a yeast cell, the button recruited the yeast’s molecular machinery to build a healthy human artificial chromosome.

In its initial circular form in yeast cells, the synthetic human chromosome could then be directly passed into human cells through a process called cell fusion. Scientists removed the “wrappers” around yeast cells with chemical treatments, allowing the cells’ components—including the artificial chromosome—to merge directly into human cells inside petri dishes.

Like benevolent extraterrestrials, the added synthetic chromosomes happily integrated into their human host cells. Rather than clumping into noxious debris, the circles doubled into a figure-eight shape, with the centromere holding the circles together. The artificial chromosomes happily co-existed with native X-shaped ones, without changing their normal functions.

For gene therapy, it’s essential that any added genes remain inside the body even as cells divide. This perk is especially important for fast-dividing cells like cancer, which can rapidly adapt to therapies. If a synthetic chromosome is packed with known cancer-suppressing genes, it could keep cancers and other diseases in check throughout generations of cells.

The artificial human chromosomes passed the test. They recruited proteins from the human host cells to help them spread as the cells divided, thus conserving the artificial genes over generations.

A Revival

Much has changed since the first human artificial chromosomes.

Gene editing tools, such as CRISPR, have made it easier to rewrite our genetic blueprint. Delivery mechanisms that target specific organs or tissues are on the rise. But synthetic chromosomes may be regaining some of the spotlight.

Unlike viral carriers, the most often used delivery vehicle for gene therapies or gene editors, artificial chromosomes can’t tunnel into our genome and disrupt normal gene expression—making them potentially far safer.

The technology has vulnerabilities though. The engineered chromosomes are still often lost when cells divide. Synthetic genes placed near the centromere—the “button” of the chromosome—may also disrupt the artificial chromosome’s ability to replicate and separate when cells divide.

But to Dawe, the study has larger implications than human cells alone. The principles of re-engineering centromeres shown in this study could be used for yeast and potentially be “applicable across kingdoms” of living organisms.

The method could help scientists better model human diseases or produce drugs and vaccines. More broadly, “It may soon be possible to include artificial chromosomes as a part of an expanding toolkit to address global challenges related to health care, livestock, and the production of food and fiber,” he wrote.

Image Credit: Warren Umoh / Unsplash

Kategorie: Transhumanismus

[PDF] Data Science market Research Report 2020: size, share, opportunities, and forecast 2030

Home AI - 6 Březen, 2023 - 08:52

The Data Science Market includes a wide range of products and services, including data analytics software, data visualization tools, machine learning …