The week’s most astounding developments from the neobiological frontier.

August 5, 2021

200,000 new protein–protein interactions uncovered

Scientists at the University of California, San Diego have developed a new way to map protein–protein interactions for thousands of proteins at a time in a single experiment. Understanding how proteins interact with each other in living cells and tissues is crucial for understanding the nuances of human physiology and can reveal new molecular targets for treating different diseases. Demonstrating the power of their tool, which they call PROPER-seq, on human embryonic kidney cells, T cells, and endothelial cells, they identified 200,000 new protein–protein interactions in these cells, including more than 17,000 that had been predicted but never observed experimentally. Molecular Cell

5 million “missing” baby girls projected by 2100

Since the 1970s, the overwhelming preference for boy children in countries like China and India has led to a form of prenatal sex discrimination achieved primarily through the practice of sex-selective abortion. Examining 3.26 billion birth records since the 1970s, researchers at King Abdullah University of Science and Technology in Saudi Arabia projected two scenarios. In one, where the decades-old practice declines and fades over the next decade, the world will still see a substantial gender deficit burden by 2100, with an estimated 5.7 million “missing” girls. In the second scenario, where the practice of prenatal sex discrimination actually expands to populous countries with strong son preferences, like Nigeria or Pakistan, the burden is projected to be 22.1 missing girls, with a sizeable contribution from sub-Saharan Africa. We shudder to imagine the social and economic impacts. BMJ Global Health

The secret science of study breaks

The “spacing effect” in learning holds that taking breaks between lessons can strengthen your memory—an effect seen not just in human training but observed in creatures as far flung as mollusks and mice even though the neurobiological mechanism of this effect was never understood. Now scientists at Max Planck Institute of Neurobiology in Germany have shown how time between trials of an everyday memory task enhances learning in the mouse brain. They used neuroimaging to reveal how spacing tasks strengthens connectivity between ensembles of neurons in the dorsomedial prefrontal cortex of the mouse brain, making a memory more robust and increasing the probability of its retrieval. Current Biology

The underlying genetics of menopause

For the last two centuries, while the average life expectancy in high-income countries has increased by about 40 years, the average age of natural menopause has remained the same. Menopause, the loss of ovarian function and permanent cessation of menstrual cycles, occurs for most women when they’re around 50, and fertility usually begins to decline about 10 years before that. To figure out what determines the age of natural menopause, a collaboration of European institutions used the UK Biobank to conduct a genetic analysis of 200,000 European women. They discovered 290 genetic loci associated with age of natural menopause, which could lead to new therapeutic approaches to extend fertility and prevent health problems linked to menopause. Nature

Cholesterol metabolism in the brain and potential new ALS and dementia treatments

Despite the bad rap it receives for its role in cardiovascular disease, cholesterol is actually a critically important molecule in the central nervous system because it’s a core component of the myelin sheaths that wrap and insulate brain cells. A quarter of the body’s cholesterol is tied up in the brain, and its loss may be linked to diseases like amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), according to researchers at National University of Singapore. Looking at the action of a protein called TDP-43 in mice, they found that when it’s depleted, brain cells cannot maintain myelin, suggesting that cholesterol-modulating drugs could potentially treat these diseases. Journal of Cell Biology

Compared with a normal cell (left), an oligodendrocyte lacking TDP-43 (center) produces less myelin (green) because it is unable to synthesize or take up sufficient amounts of cholesterol. Supplementing TDP-43–deficient cells with cholesterol (right) restores myelin production. Ho et al. Originally published in Journal of Cell Biology (2021)

Dietary intervention slows Parkinson’s in mice

When someone suffers from Parkinson’s disease, their clinical progression and motor dysfunction is driven by the ongoing loss of neurons that react to dopamine in certain parts of their brain—and currently no FDA-approved drug can halt or slow this progression. But a natural chemical compound called farnesol may be able to according to a study at Johns Hopkins University and Sungkyunkwan University in South Korea. Farnesol is found in things like berries, citronella oil, and lemongrass, and it’s used industrially as a flavoring agent and scent modifier in cigarettes and lilac perfumes. In mice afflicted with Parkinson’s, it slowed the loss of neurons and alleviated their disease symptoms suggesting a potential dietary intervention as treatment. Science Translational Medicine

Including farnesol in the diets of mice that overexpressed the PARIS protein prevented the loss of neurons in the brain. A. Jo et al., Science Translational Medicine (2021)