It wasn’t until the latter half of the 13th century that human dissections became acceptable in Italy. Previously, both the Roman Empire and Islamic law had prevented the dissection of humans and its depiction. While the Greek surgeon Galen’s anatomical drawings from the second century had been preserved and studied until the Renaissance, they were largely based on dissections of animals, such as apes.

In the mid-16th century, however, famed Flemish anatomist Andreas Vesalius dissected the bodies of executed criminals—not an uncommon practice in that period—while studying in Paris. He realized that Galen had been “misled” by apes, whose anatomy was not exactly like that of humans.

“The challenge of anatomy is rendering the 3-D experience of opening bodies onto a 2-D page,” writes Hannah Marcus, a science historian at Harvard University, in an email to The Scientist. Lack of refrigeration also presented a challenge. In overcoming those hurdles to produce the first realistic depictions of internal human biology, Vesalius’s De Humani Corporis Fabrica, published in Basel, Switzerland, in 1543, galvanized the study of anatomy.

Meanwhile, Spanish-born Juan Valverde de Amusco was learning anatomy under the guidance of Roman surgeon Realdo Colombo, and possibly of Vesalius himself, at the University of Padua in Italy. Valverde observed and participated in many dissections under Colombo’s guidance, and pored over old books on the subject. He later moved to Rome and was welcomed into the home of Spanish Cardinal Juan Álvarez de Toledo.

In 1555, Valverde served as a doctor at the foremost contemporaneous Roman hospital, Santo Spirito, where many luminaries of anatomy worked during that period, including Bartolomeo Eustachi, under whom Valverde studied for a time. The following year, Valverde crafted the Spanish-language anatomical text Historia de la Composicion del Cuerpo Humano, or Account of the Composition of the Human Body. In seven parts, the book covered topics such as “bone and cartilage,” “ligaments and bandaging,” and “instruments of sensation and external motion.” Largely copied from the 1543 and 1555 editions of Vesalius’s tome, it included 15 new illustrations in four copper plates. Valverde’s book also included more than 60 corrections to Vesalius’s text, which enhanced the contemporary understanding of the intracranial passage of carotid arteries, the extraocular muscles, the stapes bone of the middle ear, and how blood moves through the septum. Historians attribute the few original illustrations to Spanish-born Gaspar Becerra.

“Vesalius was angry about Amusco’s work and accused him of plagiarism,” Marcus writes. In 1564, Vesalius wrote in his book Anatomicarum Gabrielis Fallopii Observationum Examen that “Valverde who never put his hand to a dissection and is ignorant of medicine as well as of the primary disciplines, undertook to expound our art in the Spanish language only for the sake of shameful profit.” Valverde conceded his borrowing, explaining that Vesalius’s drawings were so thorough that “it would look like envy or malignity not to take advantage of them.”

Valverde simplified Vesalius’s Latin text considerably, however, as he considered it difficult to understand. His more concise (and thus cheaper) text had more than a dozen editions published in Italian, Latin, Dutch, and Greek, in addition to Spanish, and facilitated the spread of scientific ideas and Vesalius’s modern anatomy throughout Europe and the Spanish Americas.–1556-64679




Previous research has shown that the gut-brain connection, which refers to signaling between the digestive and the central nervous systems, is based on the transport of hormones, but a study published today (September 21) in Science suggests there may be a more direct link—the vagus nerve.

This research presents “a new set of pathways that use gut cells to rapidly communicate with . . . the brain stem,” Daniel Drucker, who studies gut disorders at the Lunenfeld-Tanenbaum Research Institute in Toronto, Canada, and was not involved with the project, tells Science.

Building on an earlier study in which the team found that gut cells had synapses, the researchers injected a rabies virus, expressing green fluorescence, into the stomachs of mice and watched it travel speedily from the intestines to the rodents’ brainstems.

When they grew sensory gut cells together with neurons from the vagus nerve, the neurons moved across the dish to form synapses with the gut cells and began electrically coupling with them. Adding sugar to the dish sped up the rate of signaling between the gut and brain cells, a finding that suggests glutamate, a neurotransmitter involved in sensing taste, may be key to the process. Blocking glutamate secretion in gut cells brought these signals to a grinding halt.

“We think these findings are going to be the biological basis of a new sense,” coauthor Diego Bohórquez, an assistant professor of medicine at Duke University School of Medicine, says in a statement. “One that serves as the entry point for how the brain knows when the stomach is full of food and calories. It brings legitimacy to idea of the ‘gut feeling’ as a sixth sense.”–EaFM3BB6i_l04LL2zbvjlEHCWVwrSrks2D9Aksml-wGa9f88gfOwPhtiPCXEMJRqzu6WG53_vzEvHht0oAGylLgMANQ&_hsmi=66141129



The protein Bmal1, which helps regulate the body’s internal clock, is found in especially high levels in the brain and in skeletal muscles. Mice completely deficient in Bmal1 were known to suffer from sleep impairments, but the specifics at play weren’t clear. At the University of California, Los Angeles, Ketema Paul and colleagues looked to these mice for clues about the role Bmal1 plays in sleep regulation.

When Paul’s team restored levels of the Bmal1 protein in the mice’s brains, their ability to rebound from a night of bad sleep remained poor. However, turning on production in skeletal muscles alone enabled mice to sleep longer and more deeply to recover after sleep loss.

For decades, scientists have thought sleep was controlled purely by the brain. But the new study indicates the ability to catch up on one’s sleep after a bout of sleeplessness is locked away in skeletal muscles, not the brain—at least for mice. “I think it’s a real paradigm shift for how we think about sleep,” says John Hogenesch, a chronobiologist at Cincinnati Children’s Hospital Medical Center who discovered the Bmal1 gene but was not involved in this study.

Paul’s group also found that having too much of the Bmal1 protein in their muscles not only made mice vigilant but also invulnerable to the effects of sleep loss, so that they remained alert even when sleep-deprived and slept fewer hours to regain lost sleep. “To me, that presents a potential target where you could treat sleep disorders,” says Paul, noting that an inability to recover from sleep loss can make us more susceptible to diseases.

The paper
J.C. Ehlen et al., “Bmal1 function in skeletal muscle regulates sleep,” eLife, 6:e26557, 2017.–EaFM3BB6i_l04LL2zbvjlEHCWVwrSrks2D9Aksml-wGa9f88gfOwPhtiPCXEMJRqzu6WG53_vzEvHht0oAGylLgMANQ&_hsmi=66141129


Even when Parkinson’s patients don’t have mutations in a gene called LRRK2, more of the active enzyme the gene generates is present in their brains than in healthy brains, researchers reported last week (July 25) in Science Translational Medicine. The finding suggests that LRRK2 inhibitors could help to reduce harmful effects of the enzyme in the vast majority of Parkinson’s patients.

“This is the really interesting bit of data … the demonstration that when you look in the brains of individuals with idiopathic Parkinson’s [where the cause is unknown], that there’s evidence that LRRK2 is activated,” says Patrick Lewis, who studies Parkinson’s disease at University College London and the University of Reading in the UK. He has collaborated with one of the paper’s coauthors but was not involved in this study.

Ten percent of Parkinson’s cases have known genetic causes. Three percent of cases are due to a mutation in LRRK2, the gene encoding the LRRK2 enzyme. The enzyme is highly active in Parkinson’s patients with a mutated LRRK2 gene, and the increased enzyme activity has been linked to the development of the disease.

In the new study, Timothy Greenamyre, a professor of neurology at the University of Pittsburgh, and his team wanted to look at the level of active LRRK2 in patients without an LRRK2 mutation. “Because [LRRK2] is a low-abundance protein, people have had difficulty detecting it,” Greenamyre says. To spot active LRRK2, the researchers first developed two versions of an assay: the first detects the active enzyme and the second, the inactive enzyme. In the first detection method, researchers used two different antibodies, one that binds to a specific subunit that acts as a known indicator of the active enzyme and another that binds to a different proximal portion of it. When both antibodies bind successfully, their close contact generates a fluorescent signal—a sign of active LRRK2. The second method detects a protein known to regulate LRRK2 activity. Higher levels of this protein indicate lower levels of available active LRRK2.

The team used the assay on postmortem brain tissue from Parkinson’s disease patients and from healthy individuals. The researchers observed higher levels of the active LRRK2 enzyme in substantia nigra dopamine-producing neurons—the death of which indicate neurodegenerative disease—in the brain tissue of Parkinson’s patients’ with no mutation in the LRRK2 gene than in healthy brain tissue.

“We have been wondering for a very long time whether LRRK2 plays a role in sporadic Parkinson’s disease,” says Mark Cookson, who studies the neurodegenerative disorder in the National Institutes of Health’s Laboratory of Neurogenetics. He has collaborated with Greenamyre before but was not involved in this work. According to Cookson, this study provides “defensive evidence” of LRRK2’s role in the disease, even in patients without a mutation in the gene.

In the next set of experiments, Greenamyre and his colleagues wanted to see if active LRRK2 turned up in two rat models of Parkinson’s disease. In the first rodent model, the animals were given the toxin rotenone to induce symptoms of the disease. Even without a mutation in the LRRK2 gene, the rats had higher levels of active LRRK2 protein. In the rats’ brains, the active LRRK2 enzymes were linked with clumps of another protein, α-synuclein. The clumps eventually help form Lewy bodies, a characteristic feature of Parkinson’s brains. In the second rodent model, the researchers overexpressed wildtype α-synuclein in the rats’ substantia nigra, which caused levels of active LRRK2 to rise. When the group treated the rotenone-rodent model with a drug that inhibited the LRRK2 protein, the number of clumps and Lewy bodies dropped.

The team also observed higher levels of reactive oxygen species (ROS)—chemically responsive molecules such as peroxides—in the brains of both rat models of Parkinson’s disease. As a result, Greenamyre and his colleagues wanted to see if directly increasing ROS led to more active LRRK2. In a third set of experiments, the team dosed healthy human cell lines with hydrogen peroxide and found the addition of the ROS increased the levels of LRRK2. A spike in ROS levels, the researchers suggest, activates LRRK2, which in turn aids in the development of some classic Parkinson’s features. Blocking the production of ROS resulted in a drop in active LRRK2. The result gives clues to an environmental cause for Parkinson’s disease.

Pharmaceutical companies are already developing LRRK2 inhibitors that can help the small percentage of Parkinson’s patients that have a mutation in the LRRK2 gene. “The inhibitors may benefit patients not only with the mutation but also patients who have idiopathic diseases—they’re much more common,” says coauthor Dario Alessi, a professor who studies signaling pathways in neurodegenerative disorders at the University of Dundee in the UK.

LRRK2 inhibitors, the researchers note, cause mild, yet reversible side effects, in the lungs and kidneys.

R.D. Maio et al., “LRRK2 activation in idiopathic Parkinson’s disease,” Science Translational Medicine, doi:10.1126/scitranslmed.aar5429, 2018.