Group items tagged

The new study provides “unassailable” evidence that the central nervous system can control the peripheral immune system, Tracey says. “It’s an incredibly important contribution to the fields of neuroscience and immunology.”

Just as researchers have traced sensory and motor processing to specific brain regions, Tracey suspects that a similar neurological “map” of immunologic information also exists. This new study, he says, is the first direct evidence of that map. “It’s going to be really exciting to see what comes next,” he adds.

The Sinclair group's NAD paper drew attention partly because it showed a novel way that NAD and sirtuins work together. The researchers discovered that cells' nuclei send signals to mitochondria that are needed to maintain their normal operation. SIRT1 helps insure the signals get through. When NAD levels drop, as they do with aging, SIRT1 activity falls off, which in turn makes the crucial signals fade, leading to mitochondrial dysfunction and all the ill effects that go with it.

Test-tube and rodent studies also suggest that pterostilbene is more potent than resveratrol when it comes to improving brain function, warding off various kinds of cancer and preventing heart disease.

"Cancers develop by a lineage, too," Alex Schier told the BBC. "Our technique can be used to follow these lineages during cancer formation - to tell us the relationships of cells within a tumour, and between the original tumour and secondary tumours formed by metastasis."

Research on differentiated kidney cells, particularly podocytes that can be cultured in the lab, may hold some answers. Although there are a few human- and mouse-derived cell lines that potentially differentiate into functional podocytes, there is a need for better cell lines and systems that mimic the in vivo situation more closely

Way added that there might be other reasons why newborns should carry immunosuppressive cells

Baby formulas contain small amounts of arginine. Sidney Morris, a biochemist from the University of Pittsburgh, said that it may be important to avoid fortifying them with extra arginine, lest it swamps the arginase activity of CD71+ cells, releases the immune system, and causes problems for the developing infants’ guts.

“Whether the precise mechanism of immunosuppression is the same or different in each of these circumstances remains to be determined,” he said.

Ahmari turned to mice and to optogenetics—whereby specific types of brain cells can be switched on and off in response to light. The cells of interest were engineered to express light-responsive ion channels, such that when the cells are exposed to light—by means of a fiber optic cable pointing a laser at the relevant brain region—the channels open, ions flood in, and nerve impulses fire.

But crucially, the teams had very slightly different targets in the striatum—the general ventral striatum in the case of Ahmari’s study and the specific fast-spiking inhibitory interneurons of the centromedial striatum in Graybiel’s study, suggesting that different neural circuits send inhibitory and stimulatory signals for certain OCD-like behaviors.

“they’ve been able to really delineate a pathway for compulsive behaviors in a more refined way than we’ve ever been able to do in humans, and that’s exciting because it points us in the direction of pathogenesis and pathophysiology of the disorder, but also . . . to new targets for potential intervention.”

found similar copy number variations in neurons derived in culture from human induced pluripotent stem cells (iPSCs)

neural progenitor cells derived from the same iPSC lines did not exhibit such abundant diversity. This suggested that the genetic variation in neurons occurred only at later stages of differentiation. And that the variation developed in a short space of time—the seven weeks it took to differentiate neurons from neural progenitors. Furthermore, the results implied that genetic variations seen in adult postmortem brains were unlikely to be a mere side effect of aging.

“Theory is beautiful and internally consistent. Biology, not so much.”

ere sending out a delayed copy of the command that another part of the brain was sending to its electric organ. The delayed signal went straight to the passive sensing system to cancel out the information from the electric pulse.

In the brain, somehow, stored memories and desires like hunger or thirst are added to information about the world, and actions are the result. This is the case for all sorts of animals, not just humans. It is thinking, at the most basic level.

These past studies of exercise and neurogenesis understandably have focused on distance running. Lab rodents know how to run. But whether other forms of exercise likewise prompt increases in neurogenesis has been unknown and is an issue of increasing interest

new study, which was published this month in the Journal of Physiology, researchers at the University of Jyvaskyla in Finland and other institutions gathered a large group of adult male rats. The researchers injected the rats with a substance that marks new brain cells and then set groups of them to an array of different workouts, with one group remaining sedentary to serve as controls.

They found very different levels of neurogenesis, depending on how each animal had exercised. Those rats that had jogged on wheels showed robust levels of neurogenesis. Their hippocampal tissue teemed with new neurons, far more than in the brains of the sedentary animals. The greater the distance that a runner had covered during the experiment, the more new cells its brain now contained. There were far fewer new neurons in the brains of the animals that had completed high-intensity interval training. They showed somewhat higher amounts than in the sedentary animals but far less than in the distance runners. And the weight-training rats, although they were much stronger at the end of the experiment than they had been at the start, showed no discernible augmentation of neurogenesis. Their hippocampal tissue looked just like that of the animals that had not exercised at all.

“sustained aerobic exercise might be most beneficial for brain health also in humans.”

Just why distance running was so much more potent at promoting neurogenesis than the other workouts is not clear, although Dr. Nokia and her colleagues speculate that distance running stimulates the release of a particular substance in the brain known as brain-derived neurotrophic factor that is known to regulate neurogenesis. The more miles an animal runs, the more B.D.N.F. it produces. Weight training, on the other hand, while extremely beneficial for muscular health, has previously been shown to have little effect on the body’s levels of B.D.N.F.

As for high-intensity interval training, its potential brain benefits may be undercut by its very intensity, Dr. Nokia said. It is, by intent, much more physiologically draining and stressful than moderate running, and “stress tends to decrease adult hippocampal neurogenesis,” she said.

These results do not mean, however, that only running and similar moderate endurance workouts strengthen the brain, Dr. Nokia said. Those activities do seem to prompt the most neurogenesis in the hippocampus. But weight training and high-intensity intervals probably lead to different types of changes elsewhere in the brain. They might, for instance, encourage the creation of additional blood vessels or new connections between brain cells or between different parts of the brain.

hippocampus,

Electrodes implanted in these patients' brains help their surgeons precisely identify the seizure foci and also provide valuable information on the brain's inner workings, Lega says.

new treatments to combat memory loss from conditions such as traumatic brain injury or Alzheimer's disease.

In addition, while rats are actively exploring an environment, place cells are further organized into "mini-sequences" that represent a virtual sweep of locations ahead of the rat. These radar-like sweeps happen roughly 8-10 times per second and are thought to be a brain mechanism for predicting immediately upcoming events or outcomes.

it was unclear how the hippocampus was able to produce such sequences.

hocolate milk

However, taking a closer look at the data, the researchers found something new: As the rats moved through these spaces, their neurons not only exhibited forward, predictive mini-sequences, but also backward, retrospective mini-sequences. The forward and backward sequences alternated with each other, each taking only a few dozen milliseconds to complete.

"In the past few decades, there's been an explosion in new findings about memory,"

Imbued with their own neurons, octopus arms can act semi-autonomously, gathering and exchanging information without routing it through the main brain.

It’s long been unclear, for instance, how the animals, just by probing their surroundings with their limbs, can distinguish something like a crab from a less edible object.

exposed to octopus ink, which is sometimes released as a “warning signal,” Dr. van Giesen said. “Maybe there is some kind of filtering of information that is important for the animal in specific situations,” like when danger is afoot, she said.

But they found that some of the cells in the animal’s suckers would shut down when

Humans, who tend to be very visual creatures, probably can’t fully appreciate the sensory nuances of a taste-sensitive arm

“Sometimes we assume in neuroscience or animal behavior, there’s only one way of doing it

But then again, most people could probably do without the metallic tang of keys every time they rummage in their pockets — or the funk that would inevitably dissuade every new parent from changing a diaper.

(Even after amputation, these adept appendages can still snatch hungrily at morsels of food.)

The cells of octopus suckers are decorated with a mixture of tiny detector proteins. Each type of sensor responds to a distinct chemical cue, giving the animals an extraordinarily refined palate that can inform how their agile arms react, jettisoning an object as useless or dangerous, or nabbing it for a snack.

That arm has all the cellular machinery to taste your tongue right back.

Each type of sensor responds to a distinct chemical cue, giving the animals an extraordinarily refined palate that can inform how their agile arms react, jettisoning an object as useless or dangerous, or nabbing it for a snack.

Octopuses certainly know how to put that processing power to good use.

By mixing and matching these proteins, cells could develop their own unique tasting profiles, allowing the octopus’s suckers to discern flavors in fine gradations, then shoot the sensation to other parts of the nervous system.

Underwater, some chemicals can travel far from their source, making it possible for some creatures to catch a whiff of their prey from afar. But for chemicals that don’t move through the ocean easily, a touch-taste strategy is handy, Dr. Bellono said.

The human gut microbiome is diverse and dominated by trillions of bacteria with as many as one-thousand different bacterial species. These microbes thrive in the harsh conditions of the gut and are heavily involved in maintaining healthy nutrition, normal metabolism, and proper immune function. They aid in the digestion of non-digestible carbohydrates, the metabolism of bile acid and drugs, and in the synthesis of amino acids and many vitamins. A number of gut microbes also produce antimicrobial substances that protect against pathogenic bacteria.

Microbiota of the oral cavity number in the millions and include archaea, bacteria, fungi, protists, and viruses. These organisms exist together and most in a mutualistic relationship with the host, where both the microbes and the host benefit from the relationship. While the majority of oral microbes are beneficial, preventing harmful microbes from colonizing the mouth, some have been known to become pathogenic in response to environmental changes. Bacteria are the most numerous of the oral microbes and include Streptococcus, Actinomyces, Lactobacterium, Staphylococcus, and Propionibacterium.

Messenger RNA is a powerful, if fickle, component of life’s building blocks — a workhorse of the cell that is also truly just a messenger, unstable and prone to degrade.

. In 1990,

That same year, a team at the University of Wisconsin startled the scientific world with a paper that showed it was possible to inject a snippet of messenger RNA into mice and turn their muscle cells into factories, creating proteins on demand.

If custom-designed RNA snippets could be used to turn cells into bespoke protein factories, messenger RNA could become a powerful medical tool. It could encode fragments of virus to teach the immune system to defend against pathogens. It could also create whole proteins that are missing or damaged in people with devastating genetic diseases, such as cystic fibrosis.

In 2005, the pair discovered a way to modify RNA, chemically tweaking one of the letters of its code, so it didn’t trigger an inflammatory response. Deborah Fuller, a scientist who works on RNA and DNA vaccines at the University of Washington, said that work deserves a Nobel Prize.

messenger RNA posed a bigger challenge than other targets.“It’s tougher — it’s a much bigger molecule, it’s much more unstable,”

Unlike fields that were sparked by a single powerful insight, Sahin said that the recent success of messenger RNA vaccines is a story of countless improvements that turned an alluring biological idea into a beneficial technology.

“This is a field which benefited from hundreds of inventions,” said Sahin, who noted that when he started BioNTech in 2008, he cautioned investors that the technology would not yield a product for at least a decade. He kept his word: Until the coronavirus sped things along, BioNTech projected the launch of its first commercial project in 2023.

“It’s new to you,” Fuller said. “But for basic researchers, it’s been long enough. . . . Even before covid, everyone was talking: RNA, RNA, RNA.”

All vaccines are based on the same underlying idea: training the immune system to block a virus. Old-fashioned vaccines do this work by injecting dead or weakened viruses

ewer vaccines use distinctive bits of the virus, such as proteins on their surface, to teach the lesson. The latest genetic techniques, like messenger RNA, don’t take as long to develop because those virus bits don’t have to be generated in a lab. Instead, the vaccine delivers a genetic code that instructs cells to build those characteristic proteins themselves.

They wanted the immune system to learn to recognize the thumb tack spike, so McLellan tasked a scientist in his laboratory with identifying genetic mutations that could anchor the protein into the right configuration. It was a painstaking process for Nianshuang Wang, who now works at a biotechnology company, Regeneron Pharmaceuticals. After trying hundreds of genetic mutations, he found two that worked. Five journals rejected the finding, questioning its significance, before it was published in 2017.

That infection opened Graham’s eyes to an opportunity. HKU1 was merely a nuisance, as opposed to a deadly pneumonia; that meant it would be easier to work with in the lab, since researchers wouldn’t have to don layers of protective gear and work in a pressurized laboratory.

Severe acute respiratory syndrome had emerged in 2003. Middle East respiratory syndrome (MERS) broke out in 2012. It seemed clear to Graham and Jason McLellan, a structural biologist now at the University of Texas at Austin, that new coronaviruses were jumping into people on a 10-year-clock and it might be time to brace for the next one.

Last winter, when Graham heard rumblings of a new coronavirus in China, he brought the team back together. Once its genome was shared online by Chinese scientists, the laboratories in Texas and Maryland designed a vaccine, utilizing the stabilizing mutations and the knowledge they had gained from years of basic research — a weekend project thanks to the dividends of all that past work.

Graham needed a technology that could deliver it into the body — and had already been working with Moderna, using its messenger RNA technology to create a vaccine against a different bat virus, Nipah, as a dress rehearsal for a real pandemic. Moderna and NIH set the Nipah project aside and decided to go forward with a coronavirus vaccine.

On Jan. 13, Moderna’s Moore came into work and found her team already busy translating the stabilized spike protein into their platform. The company could start making the vaccine almost right away because of its experience manufacturing experimental cancer vaccines, which involves taking tumor samples and developing personalized vaccines in 45 days.

At BioNTech, Sahin said that even in the early design phases of its vaccine candidates, he incorporated the slight genetic changes designed in Graham’s lab that would make the spike look more like the real thing. At least two other companies would incorporate that same spike.

If all goes well with regulators, the coronavirus vaccines have the makings of a pharmaceutical industry fairy tale. The world faced an unparalleled threat, and companies leaped into the fight. Pfizer plowed $2 billion into the effort. Massive infusions of government cash helped remove the financial risks for Moderna.

But the world will also owe their existence to many scientists outside those companies, in government and academia who pursued ideas they thought were important even when the world doubted them

Some of those scientists will receive remuneration, since their inventions are licensed and integrated into the products that could save the world.

As executives become billionaires, many scientists think it is fair to earn money from their inventions that can help them do more important work. But McLellan’s laboratory at the University of Texas is proud to have licensed an even more potent version of their spike protein, royalty-free, to be incorporated into a vaccine for low and middle income countries.

“They’re using the technology that [Kariko] and I developed,” he said. “We feel like it’s our vaccine, and we are incredibly excited — at how well it’s going, and how it’s going to be used to get rid of this pandemic.”

“People hear about [vaccine progress] and think someone just thought about it that night. The amount of work — it’s really a beautiful story of fundamental basic research,” Fauci said. “It was chancy, in the sense that [the vaccine technology] was new. We were aware there would be pushback. The proof in the pudding is a spectacular success.”

The Vaccine Research Center, where Graham is deputy director, was the brainchild of Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases. It was created in 1997 to bring together scientists and physicians from different disciplines to defeat diseases, with a heavy focus on HIV.

the pandemic wasn’t a sudden eureka moment — it was a catalyst that helped ignite lines of research that had been moving forward for years, far outside the spotlight of a global crisis.

In support of that idea, half a dozen Nobel laureates and other prominent scientists are working with two small companies offering NR supplements.

This time his lab made headlines by reporting that the mitochondria in muscles of elderly mice were restored to a youthful state after just a week of injections with NMN (nicotinamide mononucleotide), a molecule that naturally occurs in cells and, like NR, boosts levels of NAD.

It should be noted, however, that muscle strength was not improved in the NMN-treated mice

a single dose of NR resulted in statistically significant increases” in NAD in humans—the first evidence that supplements could really boost NAD levels in people.

When NAD levels drop, as they do with aging, SIRT1 activity falls off, which in turn makes the crucial signals fade, leading to mitochondrial dysfunction and all the ill effects that go with it.

NAD boosters might work synergistically with supplements like resveratrol to help reinvigorate mitochondria and ward off diseases of aging

Test-tube and rodent studies also suggest that pterostilbene is more potent than resveratrol when it comes to improving brain function, warding off various kinds of cancer and preventing heart disease.

Even before Sinclair's paper, researchers had shown in 2012 that when given doses of NR, mice on high-fat diets gained 60 percent less weight than they did on the same diets without NR. Further, none of the mice on NR showed signs of diabetes, and their energy levels improved. The scientists reportedly characterized NR's effects on metabolism as "nothing short of astonishing."

A decade ago, he moved from Brandeis to Columbia, which now has one of the biggest groups of theoretical neuroscientists in the world, he says, and which has a new university-wide focus on integrating brain science with other disciplines.

a “pioneer of computational neuroscience.” Mr. Abbott brought the mathematical skills of a physicist to the field, but he is able to plunge right into the difficulties of dealing with actual brain experiments

the goal is to discover the physiological mechanism in the data.

For example, he asks why does one pattern of neurons firing “make you jump off the couch and run out the door and others make you just sit there and do nothing?” It could be, Dr. Abbott says, that simultaneous firing of all the neurons causes you to take action. Or it could be that it is the number of neurons firing that prompts an action.

“We’ve looked at the nervous system from the two ends in,” Dr. Abbott said, meaning sensations that flow into the brain and actions that are initiated there. “Somewhere in the middle is really intelligence, right? That’s where the action is.”

In the brain, somehow, stored memories and desires like hunger or thirst are added to information about the world, and actions are the result. This is the case for all sorts of animals, not just humans. It is thinking, at the most basic level.

The guilt I felt about this compelled me to objectively review the literature on mRNA vaccines. Not being an expert in virology or biochemistry, I realized I had to quickly master unfamiliar words like “transfection” and concepts about gene sequences. Slowly, the information I was devouring started changing my beliefs.

I learned that research into using mRNA for vaccinations and cancer therapies has been ongoing for the past 30 years. Trial and error have refined this modality so that it was almost fully fledged by the time Covid hit

The mRNA from the vaccine is broken down quickly in our cells, and the coronavirus spike protein is expressed only transiently on the cell surface.

Furthermore, this type of vaccine is harnessing a technique that viruses already use.

It was humbling to have to change my mind. As I booked my vaccination time slot, I realized how lucky I am to have access to all this research, as well as the training to understand it.

As medical professionals, we cannot afford to be paternalistic and trust that people will follow advice without all the facts. This is especially true in Australia, where the vast majority of us have never witnessed firsthand the ravages that this disease can inflict.

Like all new converts, I am now a true believer: I’d like everyone to be vaccinated. But autonomy is a precious tenet of a free society, and I’m glad the ethicists have advised against mandating the vaccine

just hope that with more robust discussion and the wider dissemination of scientific knowledge, we may sway people like me — who have what may be valid reservations — to get the vaccine.

. “Any successful virus has to get beyond that first defense system. The more successful it is at doing that, the better off the virus is.”

A lot of researchers focused their attention on the nine mutations that alter the so-called spike protein that covers the coronavirus and allows it to invade cells

They found that lung cells with Alpha made drastically less interferon, a protein that switches on a host of immune defenses.

It’s making itself more invisible,”

They found that Alpha-infected cells make a lot of extra copies — some 80 times more than other versions of the virus — of a gene called Orf9b.

dampening the production of interferon and a full immune response. The virus, protected from attack, has better odds of making copies of itself.

people infected with Alpha have a more robust reaction than they would with other variants, coughing and shedding virus-laden mucus from not only their mouths, but also their noses — making Alpha even better at spreading.

. They may have independently evolved their own tricks for manipulating our immune system.

But studies on people who recover naturally from Covid-19 have shown that their immune systems learn to recognize other viral proteins, including Orf9b.

“It’s quite a tricky enterprise, but becoming more possible as we learn more,”