Biologists identify targets for new pancreatic cancer treatments

biologists-identify-targets-for-new-pancreatic-cancer-treatments

Researchers from MIT and Dana-Farber Cancer Institute have discovered that a class of peptides expressed in pancreatic cancer cells could be a promising target for T-cell therapies and other approaches that attack pancreatic tumors.

Known as cryptic peptides, these molecules are produced from sequences in the genome that were not thought to encode proteins. Such peptides can also be found in some healthy cells, but in this study, the researchers identified about 500 that appear to be found only in pancreatic tumors.

The researchers also showed they could generate T cells targeting those peptides. Those T cells were able to attack pancreatic tumor organoids derived from patient cells, and they significantly slowed down tumor growth in a study of mice.

“Pancreas cancer is one of the most challenging cancers to treat. This study identifies an unexpected vulnerability in pancreas cancer cells that we may be able to exploit therapeutically,” says Tyler Jacks,

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Dopamine signals when a fear can be forgotten

dopamine-signals-when-a-fear-can-be-forgotten

Dangers come but dangers also go, and when they do, the brain has an “all-clear” signal that teaches it to extinguish its fear. A new study in mice by MIT neuroscientists shows that the signal is the release of dopamine along a specific interregional brain circuit. The research therefore pinpoints a potentially critical mechanism of mental health, restoring calm when it works, but prolonging anxiety or even post-traumatic stress disorder when it doesn’t.

“Dopamine is essential to initiate fear extinction,” says Michele Pignatelli di Spinazzola, co-author of the new study from the lab of senior author Susumu Tonegawa, Picower Professor of biology and neuroscience at the RIKEN-MIT Laboratory for Neural Circuit Genetics within The Picower Institute for Learning and Memory at MIT, and a Howard Hughes Medical Institute (HHMI) investigator.

In 2020, Tonegawa’s lab showed that learning to be afraid, and then learning when that’s no longer necessary,

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New molecular label could lead to simpler, faster tuberculosis tests

new-molecular-label-could-lead-to-simpler,-faster-tuberculosis-tests

Tuberculosis, the world’s deadliest infectious disease, is estimated to infect around 10 million people each year, and kills more than 1 million annually. Once established in the lungs, the bacteria’s thick cell wall helps it to fight off the host immune system.

Much of that cell wall is made from complex sugar molecules known as glycans, but it’s not well-understood how those glycans help to defend the bacteria. One reason for that is that there hasn’t been an easy way to label them inside cells.

MIT chemists have now overcome that obstacle, demonstrating that they can label a glycan called ManLAM using an organic molecule that reacts with specific sulfur-containing sugars. These sugars are found in only three bacterial species, the most notorious and prevalent of which is Mycobacterium tuberculosis, the microbe that causes TB.

After labeling the glycan, the researchers were able to visualize where it is located within the bacterial cell wall,

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New model predicts a chemical reaction’s point of no return

new-model-predicts-a-chemical-reaction’s-point-of-no-return

When chemists design new chemical reactions, one useful piece of information involves the reaction’s transition state — the point of no return from which a reaction must proceed.

This information allows chemists to try to produce the right conditions that will allow the desired reaction to occur. However, current methods for predicting the transition state and the path that a chemical reaction will take are complicated and require a huge amount of computational power.

MIT researchers have now developed a machine-learning model that can make these predictions in less than a second, with high accuracy. Their model could make it easier for chemists to design chemical reactions that could generate a variety of useful compounds, such as pharmaceuticals or fuels.

“We’d like to be able to ultimately design processes to take abundant natural resources and turn them into molecules that we need, such as materials and therapeutic drugs.

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A brief history of expansion microscopy

a-brief-history-of-expansion-microscopy

Nearly 150 years ago, scientists began to imagine how information might flow through the brain based on the shapes of neurons they had seen under the microscopes of the time. With today’s imaging technologies, scientists can zoom in much further, seeing the tiny synapses through which neurons communicate with one another, and even the molecules the cells use to relay their messages. These inside views can spark new ideas about how healthy brains work and reveal important changes that contribute to disease.

This sharper view of biology is not just about the advances that have made microscopes more powerful than ever before. Using methodology developed in the lab of MIT McGovern Institute for Brain Research investigator Edward Boyden, researchers around the world are imaging samples that have been swollen to as much as 20 times their original size so their finest features can be seen more clearly.

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Making AI-generated code more accurate in any language

making-ai-generated-code-more-accurate-in-any-language

Programmers can now use large language models (LLMs) to generate computer code more quickly. However, this only makes programmers’ lives easier if that code follows the rules of the programming language and doesn’t cause a computer to crash.

Some methods exist for ensuring LLMs conform to the rules of whatever language they are generating text in, but many of these methods either distort the model’s intended meaning or are too time-consuming to be feasible for complex tasks.

A new approach developed by researchers at MIT and elsewhere automatically guides an LLM to generate text that adheres to the rules of the relevant language, such as a particular programming language, and is also error-free. Their method allows an LLM to allocate efforts toward outputs that are most likely to be valid and accurate, while discarding unpromising outputs early in the process. This probabilistic approach boosts computational efficiency.

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