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Cell Metabolism

Why antidepressants do not work for everyone

In two recent editions of Molecular Psychiatry, Rusty Gage, first author Krishna Vadodaria and collaborators showed why selective serotonin reuptake inhibitors (SSRIs), a common treatment for major depressive disorder that increases the neurotransmitter serotonin, do not work in some patients. The discoveries could help lead to more personalized treatments for depression as well as other psychiatric conditions, such as bipolar disorder and schizophrenia. In the first study, published in January, the researchers created neurons from skin cells from patients whose depression did not show signs of improving with SSRIs. The team discovered that these patient-derived neurons became hyperactive when serotonin levels increased, compared with cells derived from healthy individuals or those who respond to SSRIs.

In March, a second paper by the group demonstrated that neurons from SSRI-resistant patients had longer neuron projections than did neurons from SSRI-responders, along with low levels of key genes involved in forming brain circuits.

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Read March News Release

Uncovering the evolution of the brain

What makes us human, and where does this mysterious property of “humanness” come from? President and Professor Rusty Gage, along with co-first author Carol Marchetto and colleagues, developed a strategy to more easily study the early development of human neurons compared with the neurons of nonhuman primates. The research offers scientists a novel tool to construct an evolutionary tree of multiple primate species to better understand the evolution of the human brain.

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Nature Medicine

Putting the brakes on aging

Professor Juan Carlos Izpisua Belmonte, co-first author Hsin-Kai Liao and colleagues developed a novel CRISPR/Cas9 genome-editing therapy that can suppress the accelerated aging observed in mice with Hutchinson-Gilford progeria syndrome, a rare genetic disorder that also afflicts humans. The treatment provides insight into the molecular pathways involved in accelerated aging, as well as how gene therapy can be used to reduce toxic proteins.

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Redox Biology

Native California medicinal plant may hold promise for treating Alzheimer’s

The medicinal powers of aspirin, digitalis and the anti-malarial artemisinin come from plants. Members of the lab of Professor David Schubert, including senior author Pamela Maher and first author Wolfgang Fisher, discovered a potent neuroprotective and anti-inflammatory chemical in a shrub native to California that may lead to a treatment for Alzheimer’s disease.

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Salk scientists uncover how high-fat diets drive colorectal cancer growth

Deaths from colorectal cancer in people under 55 are increasing. A new study led by Professor Ronald Evans, with first author Ting Fu and collaborators, suggests that high-fat diets fuel colorectal cancer growth by upsetting the balance of bile acids in the intestine and triggering a hormonal signal that lets cancerous cells thrive. The findings could explain why colorectal cancer is being seen in younger people growing up at a time when high-fat diets are common.

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How attention helps the brain perceive objects

Scientists have long theorized that attention to a particular object can alter perception by amplifying specific neuronal activity and suppressing the activity of other neurons (brain “noise”). Professor John Reynolds, first author Anirvan Nandy and collaborators confirmed this theory by showing how too much background noise from neurons can interrupt focused attention and cause the brain to struggle to perceive objects. The findings could help improve designs for visual prosthetics.

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PLOS Genetics

Guardians of the synapse: scientists identify a new role for nerve-supporting cells

Salk Professor Kuo-Fen Lee, first author Thomas Gould and collaborators found that a blood-clotting protein can unexpectedly degrade nerves—and discovered how nerve-supporting glial cells, including Schwann cells, provide protection from this degradation. The findings show that Schwann cells protect nerves by blocking the blood-clotting protein as well as other potentially destructive enzymes released by muscle cells. The work could have implications for diseases as diverse as amyotrophic lateral sclerosis, multiple sclerosis, Alzheimer’s disease and schizophrenia.

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Genes and Development

New role for a driver of metastatic cancers

Metastatic cancers are notoriously difficult to treat and often deadly. Professor Katherine Jones, first author Seung Choi and colleagues revealed a new role for a protein called CDK12. By analyzing the role of CDK12 in protecting cells from chemotherapy, the team discovered a new group of genes that controls cancer-cell metabolism. CDK12 works with another protein, mTORC1, to control the process of translation—an important step in creating a new protein within the cell. This finding points to a potential new metastatic drug target.

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Like mountaineers, nerves need expert guidance to find their way

Similar to the dozens of Sherpas who guide hikers up treacherous Himalayan mountains to reach a summit, the nervous system relies on elaborate timing and location of guidance cues for neuronal axons—threadlike projections—to successfully reach their destinations in the body. Professor Samuel Pfaff, first author Dario Bonanomi and collaborators discovered how neurons listen for directions and simultaneously filter out inappropriate instructions to navigate tricky cellular environments.

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New study targets achilles’ heel of pancreatic cancer

Advanced pancreatic cancer is often symptomless, leading to late diagnosis after metastases have spread throughout the body. Additionally, tumor cells are encased in a protective shield, a microenvironment conferring resistance to many cancer drugs. Professor Tony Hunter, first author Yu Shi and an international team of collaborators uncovered the role of a signaling protein, LIF, that may be a useful biomarker to help diagnose pancreatic cancer more quickly and efficiently than current screenings methods.

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Cell Metabolism

How old are your organs? To scientists’ surprise, organs are a mix of young and old cells

Vice President, Chief Science Officer and Professor Martin Hetzer, first author Rafael Arrojo e Drigo and colleagues discovered that the mouse brain, liver and pancreas contain populations of cells and proteins with extremely long life spans—some as old as the organism itself. The team’s methods could be applied to nearly any tissue in the body to provide valuable information about the lifelong function of nondividing cells and how cells lose control over the quality of proteins and cell structures during aging.

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