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In a major breakthrough, researchers at Massachusetts General Hospital (MGH) have discovered how amyloid beta—the neurotoxin believed to be at the root of Alzheimer’s disease (AD)—forms in axons and related structures that connect neurons in the brain, where it causes the most damage. Their findings, published in Cell Reports, could serve as a guidepost for developing new therapies to prevent the onset of this devastating neurological disease.

Among his many contributions to research on AD, Rudolph Tanzi, Ph.D., vice chair of Neurology and co-director of the McCance Center for Brain Health at MGH, led a team in 1986 that discovered the first Alzheimer’s disease gene, known as APP, which provides instructions for making amyloid protein precursor (APP). When this protein is cut (or cleaved) by enzymes—first, beta secretase, followed by gamma secretase—the byproduct is amyloid beta (sometimes shortened to Abeta). Large deposits of amyloid beta are believed to cause neurological destruction that results in AD. Amyloid beta formed in the brain’s axons and nerve endings causes the worst damage in AD by impairing communication between nerve cells (or neurons) in the brain. Researchers around the world have worked intensely to find ways to block the formation of amyloid beta by preventing cleavage by beta secretase and gamma secretase. However, these approaches have been hampered by safety issues.

Despite years of research, a major mystery has remained. “We knew that Abeta is made in the axons of the brain’s nerve cells, but we didn’t know how,” says Tanzi. He and his colleagues probed the question by studying the brains of mice, as well as with a research tool known as Alzheimer’s in a dish, a three-dimensional cell culture model of the disease created in 2014 by Tanzi and a colleague, Doo Yeon Kim, Ph.D. Earlier, in 2013, several other MGH researchers, including neurobiologist Dora Kovacs, Ph.D. (who is married to Tanzi), and Raja Bhattacharyya, Ph.D., a member of Tanzi’s lab, showed that a form of APP that has undergone a process called palmitoylation (palAPP) gives rise to amyloid beta. That study indicated that, within the neuron, palAPP is transported in a fatty vesicle (or sac) known as a lipid raft. But there are many forms of lipid rafts.

Researchers with the BrainGate Collaboration have deciphered the brain activity associated with handwriting: working with a 65-year-old (at the time of the study) participant with paralysis who has sensors implanted in his brain, they used an algorithm to identify letters as he attempted to write them; then, the system displayed the text on a screen; by attempting handwriting, the participant typed 90 characters per minute — more than double the previous record for typing with a brain-computer interface.

So far, a major focus of brain-computer interface research has been on restoring gross motor skills, such as reaching and grasping or point-and-click typing with a computer cursor.

Scientists modify CAR T-Cell therapy, making it more effective and less toxic, for possible use in solid tumors such as neuroblastoma.

Chimeric Antigen Receptor T-cell therapy — CAR T — has revolutionized leukemia treatment. Unfortunately, the therapy has not been effective for treating solid tumors including childhood cancers such as neuroblastoma. Preclinical studies using certain CAR T against neuroblastoma revealed toxic effects. Now, a group of scientists at Children’s Hospital Los Angeles have developed a modified version of CAR T that shows promise in targeting neuroblastoma, spares healthy brain tissue and more effectively kills cancer cells. Their study was published today in Nature Communications. While this work is in the preclinical phase, it reveals potential for lifesaving treatment in children and adults with solid tumors.

Shahab Asgharzadeh, MD, a physician scientist at the Cancer and Blood Disease Institute of CHLA, is working to improve the lifesaving CAR T-cell therapy, in which scientists take a patient’s own immune system T-cells and engineer them to recognize and destroy cancer cells.

“The CAR T therapy works in leukemia,” he says, “by targeting a unique protein (or antigen) on the surface of leukemia cells. When the treatment is given, leukemia cells are killed. CAR T turns the patient’s immune system into a powerful and targeted cancer-killer in patients with leukemia. This antigen is also on normal B cells in the blood, but this side effect can be treated medically.”

The Latest Research

Two active forms of vitamin B12 offer support to the aging brain. Preclinical data shows one of the forms protects dopamine levels.

By Michael Downey.

And cells from people with mutations in KMT2D, which results in Kabuki syndrome, showed similar patterns of activity to the EHMT1 cells. Kabuki syndrome often results in intellectual disability but is not typically linked to autism.

Cells that carry mutations in ARID1B showed a distinct pattern of network activity, with short, small bursts occurring at an unusually high rate.

Moving forward, Nadif Kasri and his colleagues plan to test other genes that increase a person’s likelihood of being autistic. They also plan to explore how these activity patterns compare at the individual level, and how they relate to other autism-linked traits, he says.

Criticism of a recent video denouncing resveratrol.

Following Doctor Brad Stanfield’s latest ‘why I stopped video’, this last one about resveratrol and pterostilbene, many of you asked for my opinion, well here it is.

Continue reading “Why Dr. Brad Stanfield Needed to Apologize” »

Humans are distinguished from other species by several aspects of cognition. While much comparative evolutionary neuroscience has focused on the neocortex, increasing recognition of the cerebellum’s role in cognition and motor processing has inspired considerable new research. Comparative molecular studies, however, generally continue to focus on the neocortex. We sought to characterize potential genetic regulatory traits distinguishing the human cerebellum by undertaking genome-wide epigenetic profiling of the lateral cerebellum, and compared this to the prefrontal cortex of humans, chimpanzees, and rhesus macaque monkeys. We found that humans showed greater differential CpG methylation–an epigenetic modification of DNA that can reflect past or present gene expression–in the cerebellum than the prefrontal cortex, highlighting the importance of this structure in human brain evolution. Humans also specifically show methylation differences at genes involved in neurodevelopment, neuroinflammation, synaptic plasticity, and lipid metabolism. These differences are relevant for understanding processes specific to humans, such as extensive plasticity, as well as pronounced and prevalent neurodegenerative conditions associated with aging.

Citation: Guevara EE, Hopkins WD, Hof PR, Ely JJ, Bradley BJ, Sherwood CC (2021) Comparative analysis reveals distinctive epigenetic features of the human cerebellum. PLoS Genet 17: e1009506. https://doi.org/10.1371/journal.pgen.

Editor: Takashi Gojobori, National Institute of Genetics, JAPAN.

Symptoms include hallucinations, muscle and brain atrophy and Capgras delusion, a belief that family members have been replaced by impostors.

History tells us that games are an inseparable facet of humanity, and mainly for good reasons. Advocates of video games laud their pros: they help develop problem-solving skills, socialize, relieve stress, and exercise the mind and body—all at the same time! However, games also have a dark side: the potential for addiction. The explosive growth of the video game industry has spawned all sorts of games targeting different groups of people. This includes digital adaptations of popular board games like chess, but also extends to gambling-type games like online casinos and betting on horse races. While virtually all engaging forms of entertainment lend themselves to addictive behavior under specific circumstances, some video games are more commonly associated with addiction than others. But what exactly makes these games so potentially addictive?

This is a difficult question to answer because it deals directly with aspects of the human mind, and the inner workings of the mind are mostly a mystery. However, there may be a way to answer it by leveraging what we do know about the physical world and its laws. At the Japan Advanced Institute of Science and Technology (JAIST), Japan, Professor Hiroyuki Iida and colleagues have been pioneering a methodology called “motion in mind” that could help us understand what draws us towards games and makes us want to keep reaching for the console.

Their approach is centered around modeling the underlying mechanisms that operate in the mind when playing games through an analogy with actual physical models of motion. For example, the concepts of potential energy, forces, and momentum from classical mechanics are considered to be analogous to objective and/or subjective game-related aspects, including pacing of the game, randomness, and fairness. In their latest study published in IEEE Access, Professor Iida and Assistant Professor Mohd Nor Akmal Khalid, also from JAIST, linked their “motion in mind” model with the concepts of engagement and addiction in various types of games from the perceived experience of the player and their behaviors.