Caffeinated Stem Cells

Forty-one years after Sir John Gurdon was the first scientist to transfer an adult cell’s genetic material (DNA) into a DNA-less egg (work done in frogs for which Gurdon won the 2012 Nobel Prize in Physiology or Medicine), scientists have successfully removed the DNA from human eggs and replaced it with DNA from mature human cells. The resulting human embryo, for the first time ever, progressed far enough in development to enable the derivation of human embryonic stem cells. The work, done by collaborators from Oregon, Boston, and Thailand and published yesterday in Cell, presents possibilities for the development of stem cells with the exact same genetic makeup as patients to enable researchers to specifically study and treat disease.

One quirky piece of the research is that the scientists found that treating the eggs with a bit of caffeine made the transfer of adult DNA into the eggs more efficient, yielding embryos that developed more typically and from which better quality stem cells were derived.

UPDATED 23 May 2013:  This paper has received criticism for the use of several of the same images in various contexts to illustrate different characteristics of stem cells, whether certain experiments where validated by repetition in an acceptable way,  and for the quick time from submission to acceptance at Cell. The submission to acceptance time is generally on the order of months. For more about these issues read the piece at Nature and the forum on the open reviewing site PubPeer.

Neuronal Support Cells Get the Message

During motor neuron development in zebrafish, a class of glial (support) cells, called perineurial glia, migrates out of the spinal cord based on signals that have been unknown until now.  Sarah Kucenas and colleagues at the University of Virginia showed in new work, published this week in the Journal of Neuroscience, that the Notch signaling pathway plays a role in correct migration of perineurial glia and in the differentiation of Schwann cells, the cells that ensheath nerve axons. Using the zebrafish embryo, which is optically clear, the researchers visualized Notch signaling and cell migration in real time, generating convincing and beautiful evidence that perineurial glia rely on Notch signaling to move the long distances necessary for their function.

Too Much Salt

The landscape of taste receptors consists of cells responsive to sweet, sour, bitter, sodium salt, and umami tastes. Sweet and umami tastes attract animals, while sour and bitter tastes generally repulse them. Sodium salt tastes straddle the fence, in that low salt doses are attractive and high doses are aversive. Before work published online this week in Nature, how salty tastes elicit different responses was still a mystery. Charles S. Zuker and colleagues at Columbia University and the NIH showed in mice that bitter and sour taste receptors respond to highly salty tastes and then communicate to the brain that the salty taste is repulsive. Mice without functioning bitter and sour taste receptors still find salty tastes attractive, but do not find highly salty tastes repulsive.

Wallabies teach us about mammalian development

Developmental biologists have historically used mice to study the development of mammalian embryos. In work published online January 29 in Development, Stephen Frankenberg and his colleagues from the University of Melbourne, showed that embryos of the tammar wallaby, a marsupial, develop somewhat differently from mouse embryos. Some early embryonic genes seem to play similar roles in tammar and mouse, Frankenberg and colleagues showed. The protein products of other genes, however, appear in different cellular locations in tammar embryos than in mouse embryos, which suggests that these proteins may function differently in the two species and in other mammals. This work challenges established ideas and demonstrates the possibility of wider evolutionary variability in mammalian development than previously expected.

Humans and Bonobos are friendly to strangers

Apart from humans, most animals do not share with strangers. Jingzhi Tan and Brian Hare, working at Duke University, confirmed today in an article* published in PLoS One, however, that bonobos, highly social primates whose genomes are 98.7% similar to ours, also share with strangers. They further showed that bonobos preferentially share food with strangers over members of their own groups, even when sharing food leads to some loss of food or requires energy use on the part of the sharer. This preference for sharing with strangers is absent in humans, who share equally with strangers and friends, and seems to be motivated by the bonobos’ desire for novel social interaction.

*Click here to read the article and to watch videos of the bonobos in action!

Stress in Old Worms

Stanford scientists Xiao Xu and Stuart K. Kim showed this month in PLoS Genetics that a regulatory protein called egl-27 helps protect stressed and aging worms. They used a small nematode worm called C. elegans, a common model organism, to show that levels of egl-27 go up as worms get older. Furthermore, when they generated worms with extra egl-27, those worms lived longer than worms with the normal amount of egl-27. The researchers found that egl-27 binds to regions of DNA close to aging- and stress-related genes and modulates their levels to help the worms cope with aging and survive under stressful conditions. Their findings demonstrate that the aging process, usually understood as continuous deterioration, can bring protective changes in gene expression.

Understanding Habits

Researchers at MIT have shown that habits, long believed to be automatic, are actively controlled in rats by the part of the brain called the infralimbic (IL) cortex. In the study, published in the journal PNAS, the group trained rats to follow a T-maze automatically to receive a chocolate milk or sugar water reward, creating a well-ingrained habit. Then, using animals with a molecular channel called halorhodopsin expressed by cells in the IL cortex, the researchers directed light to the area with a fiber optic cable. When the light shone on the halorhodopsin-expressing neurons, it prevented them from firing, which abolished the habitual behavior. The results of the research provide new insight into how quickly habits are formed and replaced and into the parts of the brain that mediate habitual behavior.

Click for video or written explanations of their technique, called optogenetics.

Using Dogs in Research

But not for animal testing! Two studies, released this summer in PLoS One, had dogs as part of the research team.

The first study used both canine detection and animal following methods to find scat from killer whales in the inland waters close to British Columbia and Washington state. The highly sensitive canine detection method allows the researchers to follow much further behind whales in their research boats, which means the following is less likely to cause stress to the whales. These killer whales belong to a specific group whose survival could be threatened by boat traffic, inadequate food levels, and levels of toxins in their habitats. In the paper, the group measured hormone levels from fecal samples and suggested that inadequate food levels seem more likely to cause stress to killer whales than boat traffic.

The second study used both canine detection and vocalization survey (where an owl call is simulated and owls in the vicinity respond) methods to find pellets and feces from northern spotted owls, an endangered species for whom conservation efforts are largely based on establishing where they live. Because of the threat from barred owls, northern spotted owls do not always respond to vocal surveys, rendering these surveys less effective in establishing owl residency. By using canine detection methods, though, the researchers found a much higher percentage of the likely owl residents from both species.

In both studies, the handlers taught the dogs to respond to a target scent using positive reinforcement training with a play reward. The dogs in the studies were highly motivated by play, and there are great photos in this press release of Tucker, the whale scat sniffer, working hard on the research boat. These studies are not the first time the canine sense of smell has been put to work to study endangered species less invasively and are hopefully not the end of exciting collaborations between human and dog researchers.