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Researchers Use Stem Cells to Help Rats with Paraplegia Walk Again

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Spinal cord injuries (SCIs) harm the nerves housed in the spinal cord, often causing irreversible damage to the body and its functions. Normally, physicians and other clinicians can only help people adapt to their SCIs instead of healing them, but researchers at Tel Aviv University and the Technion-Israel Institute of Technology might have discovered an essential key in the search for a possible cure. Just a word of warning: this article contains descriptions of animal experimentation, so some information might not be suitable for some readers.

Dr. Shulamit Levenberg of the Technion-Israel Institute of Technology recently led a multi-university study to determine if lab rats with simulated complete spinal cord injuries could regain the use of their hind legs with the introduction of stem cells and tissue engineered scaffolds. Some stem cells had been induced to differentiate (i.e., develop into different type of cells such as support cells), while others hadn’t been induced at all. And, the scaffolds were designed to “provide a 3D environment in which cells can attach, grow and differentiate, maintain cell distribution, and provide graft protection following transplantation.” In other words, the scaffolds made sure the stem cells grew as intended and weren’t accidentally damaged.

Researchers took lab rats and surgically removed a small portion of the lamina (the bony plates of the vertebrae that protect the spinal column and the vulnerable nerves) and cut through all of the nerves. Since incomplete spinal cord injuries only damage some nerves and can, for example, leave people unable to move their legs but capable of feeling through them or vice versa, the researchers had to sever all the nerves to simulate a complete spinal cord injury. Some rats were then implanted with the scaffold and stem cells (some of which were induced and some of which were not) to bridge the severed nerves. Other rats were implanted only with the scaffold, and a control group received neither scaffold nor stem cells.

After the scaffolds and stem cells were implanted, the researchers stitched up all the rats, including the control group, and observed them for any improvements. Rats that received both the scaffold and induced stem cells recovered better than the other groups; 42% of these rats were able to walk and support their body weight with their hind legs after three weeks. Furthermore 75% of this group reacted to stimuli in their hind legs and tail. Fewer rats with the non-induced stem cells recovered as fully as the rats with the induced stem cells. Furthermore, researchers found the scaffold-only group could not respond to any stimuli in their hind legs or tail, and rats in the control group did not improve at all.

While the study demonstrates that induced stem cells coupled with tissue engineered scaffolds could potentially help people with SCIs walk again, the number of rats who fully recovered was fairly low. Still, the results are promising and lay the groundwork for future studies that might one day develop a cure for SCIs. The full article on Levenberg’s study can be found on Frontiers.

All you have to do to get my attention is talk about video games, technology, anime, and/or Dungeons & Dragons - also people in spandex fighting rubber suited monsters.

Biology

The First 3D-Printed Vegan Salmon Is In Stores

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Revo Foods’ “THE FILET – Inspired By Salmon” salmon fillet may be the first 3D-printed food to hit store shelves. said that firm CEO Robin Simsa remarked, “With the milestone of industrial-scale 3D food printing, we are entering a creative food revolution, an era where food is being crafted exactly according to customer needs.”

Mycoprotein from filamentous fungi is used to make the salmon alternative and other meat substitutes. Vitamins and omega-3 fatty acids are in the product, like in animals. Is high in protein, at 9.5 grams per 100 grams, although less than conventional salmon.

Revo Foods and Mycorena developed 3D-printable mycoprotein. Years of research have led to laser-cooked cheesecakes and stacked lab-grown meats.

One reason for this push is because printed food alternatives may make food production more sustainable, which worries the fishing sector. Overfishing reduces fish populations in 34% of worldwide fish stocks.

Over 25% of worldwide greenhouse gas emissions come from food production, with 31% from livestock and fish farms and 18% from supply chain components including processing and shipping. According to Revo Foods’ website, vegan salmon fillet production consumes 77 to 86% less carbon dioxide and 95% less freshwater than conventional salmon harvesting and processing.

The salmon alternative’s sales potential is unknown. In order to succeed, Revo Foods believes that such goods must “recreate an authentic taste that appeals to the flexitarian market.”

The commercial distribution of 3D-printed food could change food production.

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Artificial Intelligence

Open-source Microsoft Novel protein-generating AI EvoDiff

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All diseases are based on proteins, natural molecules that perform vital cellular functions. Characterizing proteins can reveal disease mechanisms and ways to slow or reverse them, while creating proteins can lead to new drug classes.

The lab’s protein design process is computationally and human resource-intensive. It involves creating a protein structure that could perform a specific function in the body and then finding a protein sequence that could “fold” into that structure. To function, proteins must fold correctly into three-dimensional shapes.

Not everything has to be complicated.

Microsoft introduced EvoDiff, a general-purpose framework that generates “high-fidelity,” “diverse” proteins from protein sequences, this week. Unlike other protein-generating frameworks, EvoDiff doesn’t need target protein structure, eliminating the most laborious step.

Microsoft senior researcher Kevin Yang says EvoDiff, which is open source, could be used to create enzymes for new therapeutics, drug delivery, and industrial chemical reactions.

Yang, one of EvoDiff’s co-creators, told n an email interview that the platform will advance protein engineering beyond structure-function to sequence-first design. EvoDiff shows that ‘protein sequence is all you need’ to controllably design new proteins.

A 640-million-parameter model trained on data from all protein species and functional classes underpins EvoDiff. “Parameters” are the parts of an AI model learned from training data that define its skill at a problem, in this case protein generation. The model was trained using OpenFold sequence alignment data and UniRef50, a subset of UniProt, the UniProt consortium’s protein sequence and functional information database.

Modern image-generating models like Stable Diffusion and DALL-E 2 are diffusion models like EvoDiff. EvoDiff slowly subtracts noise from a protein made almost entirely of noise to move it closer to a protein sequence.

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Beyond image generation, diffusion models are being used to design novel proteins like EvoDiff, create music, and synthesize speech.

“If there’s one thing to take away [from EvoDiff], I think it’s this idea that we can — and should — do protein generation over sequence because of the generality, scale, and modularity we can achieve,” Microsoft senior researcher Ava Amini, another co-contributor, said via email. “Our diffusion framework lets us do that and control how we design these proteins to meet functional goals.”

EvoDiff can create new proteins and fill protein design “gaps,” as Amini noted. A protein amino acid sequence that meets criteria can be generated by the model from a part that binds to another protein.

EvoDiff can synthesize “disordered proteins” that don’t fold into a three-dimensional structure because it designs proteins in “sequence space” rather than structure. Disordered proteins enhance or decrease protein activity in biology and disease, like normal proteins.

EvoDiff research isn’t peer-reviewed yet. Microsoft data scientist Sarah Alamdari says the framework needs “a lot more scaling work” before it can be used commercially.

“This is just a 640-million-parameter model, and we may see improved generation quality if we scale up to billions,” Alamdari emailed. WeAI emonstrated some coarse-grained strategies, but to achieve even finer control, we would want to condition EvoDiff on text, chemical information, or other ways to specify the desired function.”

Next, the EvoDiff team will test the model’s lab-generated proteins for viability. Those who are will start work on the next framework.

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Biology

Chinese Dinosaur Might Have Been as Iridescent as a Hummingbird

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Earlier this month, I wrote an article on a toy line of scientifically accurate Velociraptor action figures with plumage inspired by modern birds. I mused how impressive it would be if prehistoric raptors had been covered by feather patterns not unlike those in the toy line. Little did I know that two weeks later, researchers would reveal that some theropods had iridescent feathers that outshine David Silva’s velocifigures.

The Caihong juji, Mandarin for “rainbow with a big crest” (or just Caihong for short), was a “paravian theropod,” a clade commonly known for its winged forelimbs (even though many weren’t capable of flight) and enlarged sickle foot claws. In 2014, a farmer in the Qinlong County in the Hebei Province of Northeastern China gave a nearly complete Caihong fossil, feathers included, to The Paleontological Museum of Liaoning. Finding a complete skeleton is rare in paleontology and proved very helpful to the researchers. However, you might wonder just how scientists were able to determine the iridescent nature of the Caihong’s plumage. Two words: fossilized melanosomes.

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Melanosomes are organelles that create, store, and transport melanin, which determines the pigments/colors of animal hair, fur, skin, scales, and feathers. Upon examining the Caihong’s head, crest, and tail feathers with an electron microscope, scientists discovered platelet-shaped structures similar in shape to the melanosomes that give hummingbirds their iridescent coloring. The rest of the body feathers had melanosome structures similar to those in the grey and black feathers of penguins, which would have made for an odd sight: a duck-sized dinosaur with body feathers as drab as a raven’s and head and neck feathers more colorful than a peacock’s.

The inferred feather coloration of the Caihong is not its only unusual feature, though. The dinosaur had longer arm and leg feathers than its relatives, and its tail feathers created a “tail surface area” that was larger than the famous proto-bird the Archaeopteryx.  Furthermore, the Caihong had bony crests, which while common among most dinosaurs, are almost unheard of among paravian theropods. But, more importantly, it had proportionally long forearms, which is a feature of flight-capable theropods, even though scientists believe the Caihong didn’t fly. While this dinosaur apparently has the earliest examples of proportionally long forearms in the theropod fossil records, it still falls in line with the belief that the evolution of flight-capable feathers outpaced the evolution of flight-capable skeletons. The melanosomes, however, are the more intriguing discovery, since they are the earliest examples of “organized platlet-shaped nanostructures…in dinosaurian feathers.”

While paleontologists are confident the Caihong’s platelet structures are melanosomes, the researchers understand that their discovery is based partially on inference and could potentially be incorrect. If the structures aren’t melanosomes, well, that invalidates this entire article. But that’s what paleontology is all about: examining the evidence, creating inferences supported by that evidence, and changing those inferences when new information becomes available. Still, the concept of dinosaurs with iridescent feathers is pretty cool. If you want to learn more about the Caihong juji, you can read the original article on Nature.

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