“Given the increasing use of brain stimulation in human brain study and treatment of neurological diseases, this research can make a big impact on physicians and their patients,” said Xiaoming Jin, PhD, associate professor of anatomy, cell biology and physiology.

When someone experiences a brain injury, nerve injury, or neurodegeneration, such as in epilepsy and TBI, there is damage to the brain which can lead to loss and damage of nerve or neurons and development of hyperexcitability that underlies some neurological disorders such as neuropathic pain and epilepsy.

“The conventional treatment is mainly to try to directly inhibit such hyperexcitability,” Jin said, “but we found the initial damage of the brain or nerve system was caused by a loss of brain tissue, which causes the nervous system to compensate for loss of function by working harder, so we need to stimulate activity instead of inhibit it.”

The technique, described in a newly published paper in Neurotherapeutics, uses a new type of magnetoelectric nanoparticles that can be delivered to a specific part of the brain using a magnetic field. After, a magnetic wave can be emitted to stimulate neural activity in that particular part of the brain. The method is noninvasive, good for stimulating deep brain function and is more efficient than traditional methods of brain stimulation, without the need for genetic manipulation.

“This is the only new type of nanoparticle that allows us to effectively stimulate the brain without doing any invasive procedures,” Jin said. “We can inject the nanoparticle as a solution into the vein and then bring it to any part of the body. When you apply a magnet on the head, you can localize and deliver the nanoparticle to the targeted brain region.”

The team has been working on the technique for five years in collaboration with the University of Miami and hopes to begin studying the method in humans in the next couple of years. The study has received funding from the Defense Advanced Research Projects Agency (DARPA) of the United States Department of Defense, National Science Foundation, as well as the Indiana Clinical and Translational Sciences Institute (CTSI), which helped provide funding for a medical neuroscience graduate student, Tyler Nguyen, to participate in the research. Read the full published paper in Neurotherapeutics.

Story Source:

Materials provided by Indiana University School of Medicine. Original written by Christina Griffiths. Note: Content may be edited for style and length.

The study in Ecology Letters documents how the Anolis lizard species in the Caribbean, and the Draco lizard species in Southeast Asia, have solved the challenge of communicating with one another to defend territories and attract mates.

It found males from both species perform elaborate head bob and push up displays, and rapidly extend and retract their often large and conspicuously coloured dewlap, or throat fan, specifically in habitats with lots of wind-blown vegetation or low light.

The lizards occupy the same range of rainforest and grassland habitats, and therefore face the same problems when it comes to communicating to a potential mate or enemy in visually ‘noisy’ environments.

Remarkably, they have evolved the same strategy to cope with the same selection problems, lead author Dr Terry Ord from the Evolution & Ecology Research Centre at the UNSW School of Biological, Earth and Environmental Sciences says.

According to his research, this scenario of two unrelated lizards displaying similar behaviour shows that natural selection directs evolution towards the same common set of adaptive outcomes over and over again.

“The surprise is that lizards in both groups have evolved remarkably similar displays for communication, but they also tailor the production of those displays according to the prevailing conditions experienced at the time of display,” Dr Ord says.

“That is, increasing the speed or the length of time they spend displaying the movements as the viewing conditions deteriorate.

“Really there should be essentially innumerable ways these lizards could have adapted their displays to remain effective, and there is strong evolutionary predictions that would lead us to expect this as well.”

Dr Ord says what this study shows is that natural selection driving similarities between different species.

Formally, this is known as convergent evolution — the independent origin of similar adaptations, he says.

“It seemed that these types of convergent, common adaptations are outcomes that would only really occur among species that are closely-related in some capacity,” he says.

“The reason for this is a bit complicated and it rests on the fact that adaptations build on characteristics that a species already possesses.”

“So, the longer species have evolved independently of each other, the less likely they would evolve the same adaptive solutions if they were exposed to the same change in the environment.”

But what this study highlights, he says, is what many evolutionary ecologists have argued — that natural selection is an extremely powerful process that can override the “baggage” of past history to produce the same adaptations.

“So if arm-waving is the most effective solution to some change in the environment, then natural selection would ultimately lead to its evolution rather than a more subtle (less effective) modification to an existing vocal call,” he says.

“Evolutionary biologists are excited about convergent evolution because it gives us multiple examples of the same adaptation evolving time and time again in very different animals.?

“So it tells us what the challenges are faced by these animals and how they have solved it in terms of evolutionary adaptation.”

The study documents this independent evolution of common communication strategies amongst groups that have evolved separately from each other for hundreds of millions of years.

Dr Ord says the striking similarities in communication strategies for maintaining an effective communication system in noisy conditions has evolved in various forms in many insects, fish, frogs, birds and mammals.

“For example, increasing the volume of calls when there’s lots of acoustic background noise, or extending the length of those calls or even vibrational signals by spiders and such,” Dr Ord says .

“The fact that many other groups of animals have also evolved thesesame adaptive strategies is even more extraordinary.”

Their new study, published online on July 1, 2021 in Cell Reports Medicine, shows that both CD4+ “helper” T cells and CD8+ “killer” T cells can still recognize mutated forms of the virus. This reactivity is key to the body’s complex immune response to the virus, which allows the body to kill infected cells and stop severe infections.

“This study suggests that the impact of mutations found in the variants of concern is limited,” says LJI Professor Alessandro Sette, Dr.Bio.Sci., study senior author and member of the LJI Center for Infectious Disease and Vaccine Research. “We can presume that T cells would still be available as a line of defense against viral infection.”

The researchers emphasize that the study only addresses how the body’s T cells respond to Variants of Concern (VOCs). The researchers emphasize that several of these variants, are linked to lower levels of virus-fighting antibodies.

The current study includes data on four of the most prevalent VOCs. Ongoing studies have been expanded to a larger panel of variants, including the Delta (B.1.617.2) variant, which became prevalent after this study had been initiated. The team has also established relationships with more than 20 different laboratories around the world to help monitor T cell reactivity to VOCs.

“These variants are still a concern, but our study shows that even if there is a decrease in antibodies, as other studies have shown, the T cells remain largely unaffected,” says LJI Instructor Alba Grifoni, Ph.D. “The vaccines still work.”

The Johnson & Johnson/Janssen COVID-19 vaccine was not part of this study because it was not available at the time the study was launched.

For the new study, the researchers analyzed T cells from three different groups: people who had recovered from COVID-19, people who had received either the Moderna or Pfizer-BioNTech vaccines, and people never exposed to SARS-CoV-2 (from samples taken before the pandemic).

Both the recovered subjects and the vaccinated subjects were likely to have T cells that recognized the “ancestral lineage” of SARS-CoV-2. This was the original strain that emerged at the beginning of the pandemic; however, the virus has mutated since December 2019, and several variants have been identified as VOCs.

The question was whether people with T cells trained to recognize the ancestral strain would also recognize the new variants. The researchers tested T cell responses from the donor groups against four prominent VOCs: Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Epsilon (B.1.427/B.1.429).

The researchers found that both vaccinated individuals and the recovered patients had cross-reactive T cells that could target these variants. That is good news for anyone who has received one of the two mRNA vaccines and for anyone who has recovered from any variant of the virus.

“With this study, the underlying message is optimistic,” adds Tarke. “At least, as far as the T cell response goes, your immune system is still able to recognize these new variants and your T cells will be able to respond.”

Similar results reporting largely unaffected T cell reactivity has now been presented through independent studies published in Nature and Science Immunology.

Study co-author and LJI Professor Shane Crotty, Ph.D., says this research highlights the importance of enlisting T cells in fighting SARS-CoV-2.

“COVID vaccines do a fantastic job of making antibodies that stop SARS-CoV-2 infections, but some of the vaccines do less well at stopping infections from variants,” Crotty says. “You can think of T cells as a backup system: if the virus gets past the antibodies — if you have vaccine T cells the T cells can probably still stop the variant coronavirus infection before you get pneumonia.”

Researchers are now looking for ways to take advantage of how flexible the T cells response appears to be. With T cells already working hard to recognize SARS-CoV-2 variants, Grifoni says future “booster” shots could increase immunity by prompting the body to produce more antibodies against the variants and/or by adding additional parts of the virus recognized by T cells.

“T cell epitopes are well conserved among SARS-CoV-2 variants, so incorporating T cell targets into future COVID vaccines could be a clever way to make sure future variants can’t escape the vaccines,” adds Crotty.

There is also the possibility that current SARS-CoV-2 research may one day lead to a universal, “pan-coronavirus” vaccine. This kind of vaccine would train the body to recognize the structural details, such as elements of the spike protein, that all coronaviruses have in common.

“This research shows that a pan-coronavirus vaccine is feasible,” says Grifoni.

The group is now studying a much larger group of 12 different Variants of Concern (VOCs) and Variants of Interest (VOIs), including the Delta variant (B.1.617.2), Eta (B.1.525), Iota (B.1.526), Kappa (B.1.617.1), Lambda (C37) and the variants B.1.526.1, B.1.617.3, R1 and B.1.1.519.

Sette says he’d also like to study T cells from people who have been infected with the variants and see how those T cells react to the ancestral strain of the virus.

The study, “Impact of SARS-CoV-2 variants on the total CD4+ and CD8+ T cell reactivity in infected or vaccinated individuals” was supported by The National Institutes of Health’s National Institute of Allergy and Infectious Diseases (AI142742, 75N9301900065, 75N93019C00001 and SARS-CoV-2 Assessment of Viral Evolution program (SAVE) ), the National Institutes of Health (grants U01 CA260541-01, AI036214), UC San Diego T32s (AI007036, AI007384), the Jonathan and Mary Tu Foundation, and a Clinical and Experimental Immunology Course at the University of Genoa, Italy.

Additional study authors include John Sidney, Nils Methot, Esther Dawen Yu, Yun Zhang, Jennifer M. Dan, Paul Rubiro, Aaron Sutherland, Eric Wang, Ricardo da Silva Antunes, April Frazier, Sydney I. Ramirez, Bjoern Peters, Richard Scheuermann, Stephen A. Rawlings, Davey M. Smith and Daniela Weiskopf.

LJI findings guide COVID-19 vaccine efforts

This study was previously published online as a pre-print in March 2021. The findings were then highlighted by National Institutes of Allergy and Infectious Diseases Director Anthony Fauci, M.D., in a March 31 White House press briefing.

“We’re learning more and more that these CD4+ and CD8+ T cells are very important in that they cross-react against certain viral variants,” Fauci said.

In the time since the paper was first published, the researchers nearly tripled their patient cohort and performed an additional method of stringent statistical analysis. “We’ve also added an unexposed donor cohort,” says study first author Alison Tarke, a Ph.D. student of the University of Genoa, guested in the Sette Lab at LJI.

These immune cells are better equipped to mobilize quickly against SARS-CoV-2, the coronavirus responsible for COVID-19, if they’ve already met its gentler cousins, the scientists concluded.

The findings may help explain why some people, particularly children, seem much more resilient than others to infection by SARS-CoV-2, the coronavirus that causes COVID-19. They also might make it possible to predict which people are likely to develop the most severe symptoms of COVID-19.

The immune cells in question, called killer T cells, roam through the blood and lymph, park in tissues and carry out stop-and-frisk operations on resident cells. The study, published online July 1 in Science Immunology, showed that killer T cells taken from the sickest COVID-19 patients exhibit fewer signs of having had previous run-ins with common-cold-causing coronaviruses.

Discussions about immunity to COVID-19 often center on antibodies — proteins that can latch onto a virus before it’s able to infect a vulnerable cell. But antibodies are easily fooled, said Mark Davis, PhD, a professor of microbiology and immunology; director of Stanford’s Institute for Immunity, Transplantation and Infection; and a Howard Hughes Medical Institute investigator. Davis is the study’s senior author.

“Pathogens evolve quickly and ‘learn’ to hide their critical features from our antibodies,” said Davis, who is also the Burt and Marion Avery Family Professor. But T cells recognize pathogens in a different way, and they’re tough to fool.

Our cells all issue real-time reports on their inner state of affairs by routinely sawing up some samples of each protein they’ve made lately into tiny pieces called peptides and displaying those peptides on their surfaces for inspection by T cells.

When a killer T-cell’s receptor notices a peptide on a cell’s surface that doesn’t belong there — for example, it’s from a protein produced by an invading microorganism — the T cell declares war. It multiplies furiously, and its numerous offspring — whose receptors all target the same peptide sequence — fire up to destroy any cell carrying these telltale-peptide indications of that cell’s invasion by a pathogenic microbe.

Some of the original killer T cell’s myriad daughter cells enter a more placid state, remaining above the fray. These “memory T cells” exhibit heightened sensitivity and exceptional longevity. They persist in the blood and lymph often for decades, ready to spring into action should they ever cross paths with the peptide that generated the wave of T-cell expansion that begat them. That readiness can save valuable time in stifling a previously encountered virus or a close cousin.

As the pandemic progressed, Davis mused: “A lot of people get very sick or die from COVID-19, while others are walking around not knowing they have it. Why?”

To find out, the study’s first author, postdoctoral fellow Vamsee Mallajosyula, PhD, first confirmed that some portions of SARS-CoV-2’s sequence are effectively identical to analogous portions of one or more of the four widespread common-cold-causing coronavirus strains. Then he assembled a panel of 24 different peptide sequences that were either unique to proteins made by SARS-CoV-2 or also found on similar proteins made by one or more (or even all) of the seasonal strains.

The researchers analyzed blood samples taken from healthy donors before the COVID-19 pandemic began, meaning they’d never encountered SARS-CoV-2 — although many presumably had been exposed to common-cold-causing coronavirus strains. The scientists determined the numbers of T cells targeting each peptide represented in the panel.

They found that unexposed individuals’ killer T cells targeting SARS-CoV-2 peptides that were shared with other coronaviruses were more likely to have proliferated than killer T cells targeting peptides found only on SARS-CoV-2. The T cells targeting those shared peptide sequences had probably previously encountered one or another gentler coronavirus strain — and had proliferated in response, Davis said.

Many of these killer T cells were in “memory” mode, he added.

“Memory cells are by far the most active in infectious-disease defense,” Davis said. “They’re what you want to have in order to fight off a recurring pathogen. They’re what vaccines are meant to generate.”

Killer T cells whose receptors target peptide sequences unique to SARS-CoV-2 must proliferate over several days to get up to speed after exposure to the virus, Davis said. “That lost time can spell the difference between never even noticing you have a disease and dying from it,” he said.

To test this hypothesis, Davis and his colleagues turned to blood samples from COVID-19 patients. They found that, sure enough, COVID-19 patients with milder symptoms tended to have lots of killer-T memory cells directed at peptides SARS-CoV-2 shared with other coronavirus strains. Sicker patients’ expanded killer T-cell counts were mainly among those T cells typically targeting peptides unique to SARS-CoV-2 and, thus, probably had started from scratch in their response to the virus.

“It may be that patients with severe COVID-19 hadn’t been infected, at least not recently, by gentler coronavirus strains, so they didn’t retain effective memory killer T cells,” Davis said.

Davis noted that cold-causing seasonal coronavirus strains are rampant among children, who rarely develop severe COVID-19 even though they’re just as likely to get infected as adults are.

“Sniffles and sneezes typify the daycare setting,” he said, “and coronavirus-caused common colds are a big part of the reason. As many as 80% of kids in the United States get exposed within the first couple of years of life.”

Davis and Mallajosyula have filed, through Stanford’s Office of Technology Licensing, for patents on the technology used in this study.

Davis is a member of Stanford Bio-X, the Stanford Cardiovascular Institute, the Stanford Maternal and Child Health Research Institute, the Stanford Cancer Institute and the Stanford Wu Tsai Neurosciences Institute.

Other Stanford study co-authors are former undergraduate student Conner Ganjavi; postdoctoral scholar Saborni Chakraborty, PhD; former life science research professionals Alana McSween and Allison Nau; graduate student Ana Jimena Pavlovitch-Bedzyk; life science research professional Julie Wilhelmy; Monali Manohar, PhD, laboratory director and research scientist at the Sean N. Parker Center for Asthma and Allergy Research; and Kari Nadeau, MD, PhD, professor of pediatrics and director of the Sean N. Parker Center.

The work was funded by the National Institutes of Health (grants AI057229 and U01 AI140498); Stanford’s Institute for Immunity, Transplantation and Infection; the Howard Hughes Medical Institute; the Bill and Melinda Gates Foundation; the Sean N. Parker Center and the Sunshine Foundation.

Stanford’s Department of Microbiology and Immunology also supported the work.

Now, newresearch reveals a class of neurons in the brain’s temporal pole region that links face perception to long-term memory. It’s not quite the apocryphal grandmother neuron — rather than a single cell, it’s a population of cells that collectively remembers grandma’s face. The findings, published in Science, are the first to explain how our brains inculcate the faces of those we hold dear.

“When I was coming up in neuroscience, if you wanted to ridicule someone’s argument you would dismiss it as ‘just another grandmother neuron’ — a hypothetical that could not exist,” says Winrich Freiwald, professor of neurosciences and behavior at The Rockefeller University.

“Now, in an obscure and understudied corner of the brain, we have found the closest thing to a grandmother neuron: cells capable of linking face perception to memory.”

Have I seen that face before?

The idea of a grandmother neuron first showed up in the 1960s as a theoretical brain cell that would code for a specific, complex concept, all by itself. One neuron for the memory of one’s grandmother, another to recall one’s mother, and so on. At its heart, the notion of a one-to-one ratio between brain cells and objects or concepts was an attempt to tackle the mystery of how the brain combines what we see with our long-term memories.

Scientists have since discovered plenty of sensory neurons that specialize in processing facial information, and as many memory cells dedicated to storing data from personal encounters. But a grandmother neuron — or even a hybrid cell capable of linking vision to memory — never emerged. “The expectation is that we would have had this down by now,” Freiwald says. “Far from it! We had no clear knowledge of where and how the brain processes familiar faces.”

Recently, Freiwald and colleagues discovered that a small area in the brain’s temporal pole region may be involved in facial recognition. So the team used functional magnetic resonance imaging as a guide to zoom in on the TP regions of two rhesus monkeys, and recorded the electrical signals of TP neurons as the macaques watched images of familiar faces (which they had seen in-person) and unfamiliar faces that they had only seen virtually, on a screen.

The team found that neurons in the TP region were highly selective, responding to faces that the subjects had seen before more strongly than unfamiliar ones. And the neurons were fast — discriminating between known and unknown faces immediately upon processing the image.

Interestingly, these cells responded threefold more strongly to familiar over unfamiliar faces even though the subjects had in fact seen the unfamiliar faces many times virtually, on screens. “This may point to the importance of knowing someone in person,” says neuroscientist Sofia Landi, first author on the paper. “Given the tendency nowadays to go virtual, it is important to note that faces that we have seen on a screen may not evoke the same neuronal activity as faces that we meet in-person.”

A tapestry of grandmothers

The findings constitute the first evidence of a hybrid brain cell, not unlike the fabled grandmother neuron. The cells of the TP region behave like sensory cells, with reliable and fast responses to visual stimuli. But they also act like memory cells which respond only to stimuli that the brain has seen before — in this case, familiar individuals — reflecting a change in the brain as a result of past encounters. “They’re these very visual, very sensory cells — but like memory cells,” Freiwald says. “We have discovered a connection between the sensory and memory domains.”

But the cells are not, strictly speaking, grandmother neurons. Instead of one cell coding for a single familiar face, the cells of the TP region appear to work in concert, as a collective.

“It’s a ‘grandmother face area’ of the brain,” Freiwald says.

The discovery of the TP region at the heart of facial recognition means that researchers can soon start investigating how those cells encode familiar faces. “We can now ask how this region is connected to the other parts of the brain and what happens when a new face appears,” Freiwald asks. “And of course, we can begin exploring how it works in the human brain.”

In the future, the findings may also have clinical implications for people suffering from prosopagnosia, or face blindness, a socially isolating condition that affects about one percent of the population. “Face-blind people often suffer from depression. It can be debilitating, because in the worst cases they cannot even recognize close relatives,” Freiwald says.

“This discovery could one day help us devise strategies to help them.”