Lipids Take the Lead in Metastasis

Although metastasis is the leading cause of death among people with cancer, for the most part, researchers are stumped about which molecular signals allow malignant cells to leave primary tumors and start new ones. Two studies published in Nature this month highlight roles in metastasis for an unexpected group of molecules—lipids.

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Toward Preventing Transplant Rejection with Immunologically Matched Stem Cells

Donor stem cell–derived retinal epithelial cells whose immune proteins correspond to those of a recipient are tolerated following transplant into monkeys’ eyes, according to a report published today (September 15) in Stem Cell Reports. In an accompanying paper, the team also reports that such immune-matched retinal cells derived from humans prevent immune responses in cultured human lymphocytes.

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Zika-Associated Brain Injuries Found in Monkey Fetus

After scientists infected a pregnant pigtail macaque with Zika virus, the primate’s fetus developed brain lesions similar to those observed in some human babies born to Zika-infected mothers, the team reported yesterday (September 12) in Nature Medicine.

“Our results remove any lingering doubt that the Zika virus is incredibly dangerous to the developing fetus and provides details as to how the brain injury develops,” study coauthor Kristina Adams Waldorf of the University of Washington School of Medicine said in a statement.

 

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Toggling CRISPR Activity with a Chemical Switch

Researchers design a Cas9 enzyme that cuts DNA only in the presence of particular drug.

 

There are various ways to turn CRISPR/Cas9’s gene-editing activity on and off in cells, such as exposing tailor-made Cas9 enzymes to a particular type of light or to specific drugs. Each technique developed so far has drawbacks—either being complicated or irreversible. So researchers took inspiration from the Cre-recombinase-based method to control gene expression and built a “user-friendly” protocol for reversibly activating and inactivating CRISPR.

 

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The Two Faces of Fish Oil

The discovery of a tumor-protecting role for a fatty acid found in fish oil has sparked debate about the product’s safety.

 

Emile Voest, a professor of medical oncology and medical director of The Netherlands Cancer Institute, has spent his career studying the tumor microenvironment—cancer’s cellular backdrop, implicated in everything from a tumor’s structural support to its protection from the immune system and its resistance to cancer-treating drugs.

But it came as some surprise, Voest says, when, in the mid-2000s, he and his colleagues identified two obscure polyunsaturated fatty acids—16:4(n-3) and KHT—that seemed to induce chemoresistance in tumor-bearing mice. “It was not what I was expecting at all,” says Voest. “We had no clue what fatty acids were [or] how they worked.”

The researchers found that human mesenchymal stem cells (multipotent stromal cells already implicated in drug resistance) injected into tumor-bearing mice began secreting these fatty acids when the animals were administered cisplatin—a platinum-based drug used to treat various types of cancer. These platinum-induced fatty acids (PIFAs) had no effect on tumor growth, but neutralized the cytotoxic effects of cisplatin on tumor cells, hinting at a possible mechanism of chemoresistance in human patients receiving platinum-based therapies.

 

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Mother’s Microbiome Shapes Offspring’s Immunity

The maternal gut microbiome guides neo- and postnatal immune system development, a mouse study shows.

 

Pregnant mice expose their unborn pups to maternal gut microbes, which can affect the development of the innate immune system after birth, according to a study published today (March 17) in Science. The results challenge the notion that a pup’s own gut microbiome drives immune system development, suggesting that the molecular metabolites of the maternal microbiota are transferred to pups during gestation. This transfer of maternally derived microbial metabolites prepares the offspring’s immune system for exposure to the large variety of microbes that eventually populate the gut.

 

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Who Sleeps?

Who Sleeps?

Once believed to be unique to birds and mammals, sleep is found across the metazoan kingdom. Some animals, it seems, can’t live without it, though no one knows exactly why.

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Some sleep researchers are fond of saying that all animals sleep; that sleep is maladaptive because it takes time away from activities that appear more adaptive, such as mating, seeking food, and looking out for predators; and that no one knows the function of sleep. A good case can be made that each of these statements is false.

To say whether an animal sleeps requires that we define sleep. A generally accepted definition is that sleep is a state of greatly reduced responsiveness and movement that is homeostatically regulated, meaning that when it is prevented for a period of time, the lost time is made up—an effect known as sleep rebound. Unfortunately, the application of this definition is sometimes difficult. Can an animal sleep while it is moving and responsive? How unresponsive does an animal have to be? How much of the lost sleep has to be made up for it to be considered homeostatically regulated? Is the brain activity that characterizes sleep in humans necessary and sufficient to define sleep in other animals?

 

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Breast Milk Sugars Support Infant Gut Health

Oligosaccharides found in breast milk stimulate the activity of gut bacteria, promoting growth in two animal models of infant malnutrition.

 

Gut microbes isolated from human infants that showed stunted growth can boost growth in two animal models of malnutrition with the addition of certain breast milk–derived sugars to the animals’ diets, researchers reported. The study, published today (February 18) in Cell, identifies oligosaccharides in mammalian breast milk that appear critical for the maturation of the infant gut microbiome.

“This is an excellent study that highlights the importance of [mammalian] milk oligosaccharides for infant growth and development,” said Lars Bodeof the University of California, San Diego, who was not involved in the work.

The results could inform “work to develop tools and levers to nudge the gut microbiota into the right direction to get durable effects on infant health,” said study coauthor David Mills from the University of California, Davis.

 

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New Tests for Zika in the Works

To answer questions about the risks of Zika virus infection, researchers need better diagnostics.

As reports of Zika virus infections continue to spread through the Americas, countless questions loom. Chief among them is about the relationship between infection during pregnancy and microcephaly in babies, which has been difficult to pin down given the limitations of current diagnostics. A number of researchers are working at breakneck speed to develop immunological reagents and assays that could confirm whether a person has had a Zika infection.

“We’re trying to do the best we can to give some answers to the clinicians relatively soon,” said Nikos Vasilakis, who is developing Zika tests at the University of Texas Medical Branch in Galveston.

Currently, the standard assay for Zika viral infection is a PCR test that probes for the presence of viral RNA in a sample. While it works well to detect the virus, the pathogen’s RNA is only around for a short period of time. “By the time [patients] make it into the clinic, the virus is likely gone or it’s at the tail end, beyond the limit of detection,” said Vasilakis.

 

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