Scientists Reveal Single-Neuron Gene Landscape of the Human Brain

A team of scientists at The Scripps Research Institute (TSRI), University of California, San Diego (UC San Diego) and Illumina, Inc., has completed the first large-scale assessment of single neuronal “transcriptomes.” Their research reveals a surprising diversity in the molecules that human brain cells use in transcribing genetic information from DNA to RNA and producing proteins.

brain cell

The researchers accomplished this feat by isolating and analyzing single-neuronal nuclei from the human brain, allowing classification of 16 neuronal subtypes in the brain’s cerebral cortex, the “gray matter” involved in thought, cognition and many other functions.

“Through a wonderful scientific collaboration, we found an enormous amount of transcriptomic diversity from cell to cell that will be relevant to understanding the normal brain and its diseases such as Alzheimer’s, Parkinson’s, ALS and depression,” said TSRI Professor and neuroscientist Jerold Chun, who co-led the study with bioengineers Kun Zhang and Wei Wang of UC San Diego and Jian-Bing Fan of Illumina.

The study was published on June 24 in the journal Science.

All the Same

While parts of the cerebral cortex look different under a microscope–with different cell shapes and densities that form cortical layers and larger regions having functional roles called “Brodmann Areas”–most researchers treat neurons as a fairly uniform group in their studies.

“From a tiny brain sample, researchers often make assumptions that obtained information is true for the entire brain,” said Chun.

But the brain isn’t like other organs, Chun explained. There’s a growing understanding that individual brain cells are unique, and a possibility has been that the microscopic differences among cerebral cortical areas may also reflect unique transcriptomic differences–i.e., differences in the expressed genes, or messenger RNAs (mRNAs), which carry copies of the DNA code outside the nucleus and determine which proteins the cell makes.

To better understand this diversity, the researchers in the new study analyzed more than 3,200 single human neurons–more than 10-fold greater than prior publications–in six Brodmann Areas of one human cerebral cortex.

With the help of newly developed tools to isolate and sequence individual cell nuclei (where genetic material is housed in a cell), the researchers deciphered the minute quantities of mRNA within each nucleus, revealing that various combinations of the 16 subtypes tended to cluster in cortical layers and Brodmann Areas, helping explain why these regions look and function differently.

Neurons exhibited anticipated similarities, yet also many differences in their transcriptomic profiles, revealing single neurons with shared, as well as unique, characteristics that likely lead to differences in cellular function.

“Now we can actually point to an enormous amount of molecular heterogeneity in single neurons of the brain,” said Gwendolyn E. Kaeser, a UC San Diego Biomedical Sciences Graduate Program student studying in Chun’s lab at TSRI. Kaeser was co-first author of the study with Blue B. Lake and Rizi Ai of UC San Diego and Neeraj S. Salathia of Illumina.

Many New Questions

Interestingly, some of these differences in gene expression have roots in very early brain development taking place before birth. The researchers found markers on some neurons showing that they originated from a specific region of fetal brain called the ganglionic eminence, which generates inhibitory neurons destined for the cerebral cortex. These neurons may have particular relevance to developmental brain disorders.

The enormous transcriptomic diversity of single neurons was predicted by earlier work from Chun’s laboratory and others showing that the genomes–the DNA–of individual brain cells can be different from cell to cell. In future studies, the researchers hope to investigate how single-neuron DNA and mRNA differs in single neurons, groups and between human brains–and how these may be influenced by factors such as stress, medications or disease.

Additional authors of the study, “Neuronal subtypes and diversity revealed by single-nucleus RNA sequencing of the human brain,” were Yun C. Yung, Julian Wong, Allison Chen and Xiaoyan Sheng of TSRI; Rui Liu, Andre Wildberg, Derek Gao, Ho-Lim Fung and Song Chen of UC San Diego; and Raakhee Vijayaraghavan, Fiona Kaper, Richard Shen and Mostafa Ronaghi of Illumina.

The study was supported by the National Institutes of Health Common Fund Single Cell Analysis Program (1U01MH098977-01) and a Neuroplasticity of Aging Training Grant (5T32AG000216-24).

Hubble Confirms New Dark Spot On Neptune

New images obtained on May 16, 2016, by NASA’s Hubble Space Telescope confirm the presence of a dark vortex in the atmosphere of Neptune. Though similar features were seen during the Voyager 2 flyby of Neptune in 1989 and by the Hubble Space Telescope in 1994, this vortex is the first one observed on Neptune in the 21st century.

neptune

The discovery was announced on May 17, 2016, in a Central Bureau for Astronomical Telegrams (CBAT) electronic telegram by University of California at Berkeley research astronomer Mike Wong, who led the team that analyzed the Hubble data.

Neptune’s dark vortices are high-pressure systems and are usually accompanied by bright “companion clouds,” which are also now visible on the distant planet. The bright clouds form when the flow of ambient air is perturbed and diverted upward over the dark vortex, causing gases to likely freeze into methane ice crystals. “Dark vortices coast through the atmosphere like huge, lens-shaped gaseous mountains,” Wong said. “And the companion clouds are similar to so-called orographic clouds that appear as pancake-shaped features lingering over mountains on Earth.”

Beginning in July 2015, bright clouds were again seen on Neptune by several observers, from amateurs to astronomers at the W. M. Keck Observatory in Hawaii. Astronomers suspected that these clouds might be bright companion clouds following an unseen dark vortex. Neptune’s dark vortices are typically only seen at blue wavelengths, and only Hubble has the high resolution required for seeing them on distant Neptune.

In September 2015, the Outer Planet Atmospheres Legacy (OPAL) program, a long-term Hubble Space Telescope project that annually captures global maps of the outer planets, revealed a dark spot close to the location of the bright clouds, which had been tracked from the ground. By viewing the vortex a second time, the new Hubble images confirm that OPAL really detected a long-lived feature. The new data enabled the team to create a higher-quality map of the vortex and its surroundings.

Neptune’s dark vortices have exhibited surprising diversity over the years, in terms of size, shape, and stability (they meander in latitude, and sometimes speed up or slow down). They also come and go on much shorter timescales compared to similar anticyclones seen on Jupiter; large storms on Jupiter evolve over decades.

Planetary astronomers hope to better understand how dark vortices originate, what controls their drifts and oscillations, how they interact with the environment, and how they eventually dissipate, according to UC Berkeley doctoral student Joshua Tollefson, who was recently awarded a prestigious NASA Earth and Space Science Fellowship to study Neptune’s atmosphere. Measuring the evolution of the new dark vortex will extend knowledge of both the dark vortices themselves, as well as the structure and dynamics of the surrounding atmosphere.

The team, led by Wong, also included the OPAL team (Wong, Amy Simon, and Glenn Orton), UC Berkeley collaborators (Imke de Pater, Joshua Tollefson, and Katherine de Kleer), Heidi Hammel (AURA), Statia Luszcz-Cook (AMNH), Ricardo Hueso and Agustin Sánchez-Lavega (Universidad del Pais Vasco), Marc Delcroix (Société Astronomique de France), Larry Sromovsky and Patrick Fry (University of Wisconsin), and Christoph Baranec (University of Hawaii).

The Universe: Learning About The Future From The Distant Past

Our Universe came to life nearly 14 billion years ago in the Big Bang — a tremendously energetic fireball from which the cosmos has been expanding ever since. Today, space is filled with hundreds of billions of galaxies, including our solar system’s own galactic home, the Milky Way. But how exactly did the infant universe develop into its current state, and what does it tell us about our future?

universe

These are the fundamental questions “astrophysical archeologists” like Risa Wechsler want to answer. At the Kavli Institute for Particle Astrophysics and Cosmology (KIPAC) of Stanford and the Department of Energy’s SLAC National Accelerator Laboratory, her team combines experimental data with theory in computer simulations that dig deeply into cosmic history and trace back how matter particles clumped together to form larger and larger structures in the expanding universe.

“Most of our calculations are done at KIPAC, and computing is a crucial aspect of the collaboration between SLAC and Stanford,” says Wechsler, who is an associate professor of physics and of particle physics and astrophysics.

Wechsler’s simulated journeys through spacetime use a variety of experimental data, including observations by the Dark Energy Survey (DES), which recently discovered a new set of ultra-faint companion galaxies of our Milky Way that are rich in what is known as dark matter. The gravitational pull from this invisible form of matter affects regular matter, which plays a crucial role in the formation and growth of galaxies.

Dark energy is another key ingredient shaping the universe: It inflates the universe like a balloon at an ever-increasing rate, but researchers don’t know much about what causes the acceleration.

Two future projects will give Wechsler and other researchers new clues about the mysterious energy. The Dark Energy Spectroscopic Instrument (DESI), whose science collaboration she is leading, will begin in 2018 to turn two-dimensional images of surveys like DES into a three-dimensional map of the universe. The Large Synoptic Survey Telescope (LSST), whose ultrasensitive 3,200-megapixel digital eye is being assembled at SLAC, will start a few years later to explore space more deeply than any telescope before.

“Looking at faraway galaxies means looking into the past and allows us to measure how the growth and distribution of galaxies were affected by dark energy at different points in time,” Wechsler says. “Over the past 10 years, we’ve made a lot of progress in refining our cosmological model, which describes many of the properties of today’s universe very well. Yet, if future data caused this model to break down, it would completely change our view of the universe.”

The current model suggests that the universe is fated to expand forever, turning into a darker and darker cosmos faster and faster, with galaxies growing farther and farther apart. But is this acceleration a constant or changing property of spacetime? Or could it possibly be a breakdown of our theory of gravity on the largest scales? More data will help researchers find an answer to these fundamental questions.

The Universe Is Crowded With Black Holes

A new study published in Nature presents one of the most complete models of matter in the universe and predicts hundreds of massive black hole mergers each year observable with the second generation of gravitational wave detectors.

bl hole

The model anticipated the massive black holes observed by the Laser Interferometer Gravitational-wave Observatory. The two colliding masses created the first directly detected gravitational waves and confirmed Einstein’s general theory of relativity.

“The universe isn’t the same everywhere,” said Richard O’Shaughnessy, assistant professor in RIT’s School of Mathematical Sciences, and co-author of the study led by Krzysztof Belczynski from Warsaw University. “Some places produce many more binary black holes than others. Our study takes these differences into careful account.”

Massive stars that collapse upon themselves and end their lives as black holes, like the pair LIGO detected, are extremely rare, O’Shaughnessy said. They are less evolved, “more primitive stars,” that occur in special configurations in the universe. These stars from the early universe are made of more pristine hydrogen, a gas which makes them “Titans among stars,” at 40 to 100 solar masses. In contrast, younger generations of stars consumed the corpses of their predecessors containing heavy elements, which stunted their growth.

“Because LIGO is so much more sensitive to these heavy black holes, these regions of pristine gas that make heavy black holes are extremely important,” O’Shaughnessy said. “These rare regions act like factories for building identifiable pairs of black holes.”

O’Shaughnessy and his colleagues predict that massive black holes like these spin in a stable way, with orbits that remain in the same plane. The model shows that the alignment of these massive black holes are impervious to the tiny kick that follows the stars’ core collapse. The same kick can change the alignment of smaller black holes and rock their orbital plane.

The calculations reported in Nature are the most detailed calculations of its kind ever performed, O’Shaughnessy said. He likens the model to a laboratory for assessing future prospects for gravitational wave astronomy. Other gravitational wave astronomers are now using the model in their own investigations as well.

“We’ve already seen that we can learn a lot about Einstein’s theory and massive stars, just from this one event,” said O’Shaughnessy, also a member of the LIGO Scientific Collaboration that helped make and interpret the first discovery of gravitational waves. “LIGO is not going to see 1,000 black holes like these each year, but many of them will be even better and more exciting because we will have a better instrument–better glasses to view them with and better techniques.”

O’Shaughnessy is a member of RIT’s Center for Computational Relativity and Gravitation where he collaborates with Carlos Lousto, professor in RIT’s School of Mathematical Sciences and a member of the LIGO Scientific Collaboration.

“We feel like parents of a beautiful daughter called gravitational wave astronomy born a few months ago and seeing her grow more gorgeous by the day,” Lousto said.

Mystery Of Powerful Lightning At Sea Not Solved Completely

The mystery of why most of the most powerful lightning on Earth happens over the oceans isn’t solved, but a few of the usual suspects are no longer in custody.

mysteryofpow

It isn’t an instrument error, as some hypothesized. Nor is it the relative rarity of cloud-to-sea lightning allowing charges to build. And when it comes to cloud top heights, size apparently doesn’t matter.

It’s possible the increased presence of salt in the atmosphere plays a role, but if that is the case it probably has an accomplice. The evidence implicates ice crystal size, although air flowing back and forth along the land-sea boundary might also be involved.
“There isn’t one single mechanism that by itself justifies the stronger peak current we see in cloud-to-ground lightning over the oceans,” said Dr. Themis Chronis, a research scientist in the Earth System Science Center at The University of Alabama in Huntsville (UAH). “This process isn’t as simple as we previously thought.”

Results of this research at UAH, NASA and the Universities Space Research Association (USRA) were published recently in the Journal of Geophysical Research.

Scientists have known since the early 1990s that the initial return stroke – the flash when a leader or electric channel connects a cloud to the surface – usually has a more powerful current over the oceans than lightning over dry land. While there have been hypotheses about why that should be the case, there was no generally accepted explanation.

Chronis, NASA’s William Koshak and Bill McCaul with the USRA used lightning data from the National Lightning Detection Network to create datasets for four coastal areas: along Lake Michigan, the mid-Atlantic, the Florida peninsula and the upper Gulf Coast. Then they tracked the strength and location of each lightning strike over each of those locations.

They found a type of power curve along each of the oceanic shorelines, with the relative strength of lightning strikes starting to rise just a bit inland and continuing to rise as the strikes move out to sea until the instruments no longer are reliable. The strongest lightning was along the Gulf of Mexico during the wet season.

There was, however, no such differentiation along or over Lake Michigan. Lightning over the fresh water lake was no more powerful than lightning over the surrounding land.

So it must be the increased concentration of salt – an electrical conductor – being transported from the sea into the atmosphere, right?
Well, not entirely.

“Salinity isn’t altogether out of the question. Yet,” said Chronis.

Salt is an especially dicey suspect for causing powerful lightning because atmospheric concentrations of salt rise and fall with the seasons, but not in synch with the seasonal rise and fall of powerful lightning strokes.

It is known that storms over the oceans (and slightly inshore) tend to create larger ice crystals than inland storms. Large ice crystals can hold a more powerful electric charge, but that doesn’t explain why that extra charge isn’t discharged in routine amounts through routine lightning.

And, while the size of ice crystals might vary as much as 10 percent across the land/sea boundary, the differences in the electric discharge in lightning strokes can vary by 25 to 30 percent.

It is puzzling.

For now the cause of powerful oceanic lightning will, apparently, remain a mystery. This latest research might imply increased salinity and large ice crystals in combination with storm physics could be the cause. Any conclusive theory will probably wait for additional research and data provided by new instruments, such as the Geostationary Lightning Mapper (GLM). GLM is scheduled for launch later this year aboard NOAA’s Geostationary Operational Environmental Satellite – R Series (GOES-R) weather satellite.

An Ocean Lies A Few Kilometers Beneath Saturn’s Moon Enceladus’s Icy Surface

With eruptions of ice and water vapor, and an ocean covered by an ice shell, Saturn’s moon Enceladus is one of the most fascinating in the Solar System, especially as interpretations of data provided by the Cassini spacecraft have been contradictory until now. An international team including researchers from the Laboratoire de Planétologie Géodynamique de Nantes (CNRS/Université de Nantes/Université d’Angers), Charles University in Prague, and the Royal Observatory of Belgium[recently proposed a new model that reconciles different data sets and shows that the ice shell at Enceladus’s south pole may be only a few kilometers thick.

enceladus

This suggests that there is a strong heat source in the interior of Enceladus, an additional factor supporting the possible emergence of life in its ocean.

The study has just been published online on the website of Geophysical Research Letters.

Initial interpretations of data from Cassini flybys of Enceladus estimated that the thickness of its ice shell ranged from 30 to 40 km at the south pole to 60 km at the equator. These models were unable to settle the question of whether or not its ocean extended beneath the entire ice shell. However, the discovery in 2015 of an oscillation in Enceladus’s rotation known as a libration, which is linked to tidal effects, suggests that it has a global ocean and a much thinner ice shell than predicted, with a mean thickness of around 20 km. Nonetheless, this thickness appeared to be inconsistent with other gravity and topography data.

In order to reconcile the different constraints, the researchers propose a new model in which the top two hundred meters of the ice shell acts like an elastic shell. According to this study, Enceladus is made up successively of a rocky core with a radius of 185 km, and an internal ocean approximately 45 km deep, isolated from the surface by an ice shell with a mean thickness of around 20 km, except at the south pole where it is thought to be less than 5 km thick. In this model, the ocean beneath the ice makes up 40% of the total volume of the moon, while its salt content is estimated to be similar to that of Earth’s oceans.

All this implies a new energy budget for Enceladus. Since a thinner ice shell retains less heat, the tidal effects caused by Saturn on the large fractures in the ice at the south pole are no longer enough to explain the strong heat flow affecting this region. The model therefore reinforces the idea that there is strong heat production in Enceladus’s deep interior that may power the hydrothermal vents on the ocean floor. Since complex organic molecules, whose precise composition remains unknown, have been detected in Enceladus’s jets, these conditions appear to be favorable to the emergence of life. The relative thinness of the ice shell at the south pole could also allow a future space exploration mission to gather data, in particular using radar, which would be far more reliable and easy to obtain than with the 40 km thick ice shell initially calculated.

Newborn Giant Planet Grazes Its Star

For the past 20 years, exoplanets known as ‘hot Jupiters’ have puzzled astronomers. These giant planets orbit 100 times closer to their host stars than Jupiter does to the Sun, which increases their surface temperatures. But how and when in their history did they migrate so close to their star? Now, an international team of astronomers has announced the discovery of a very young hot Jupiter orbiting in the immediate vicinity of a star that is barely two million years old — the stellar equivalent of a week-old infant. This first-ever evidence that hot Jupiters can appear at such an early stage represents a major step forward in our understanding of how planetary systems form and evolve.

planet

The work, led by researchers at the Institut de Recherche en Astrophysique et Planétologie (IRAP, CNRS/Université Toulouse III — Paul Sabatier)[1], in collaboration, amongst others[2], with colleagues at the Institut de Planétologie et d’Astrophysique de Grenoble (CNRS/Université Grenoble Alpes)[3], is published on 20 June 2016 in the journal Nature.

It was while monitoring a star barely two million years old called V830 Tau, located in the Taurus stellar nursery some 430 light years away, that an international team of astronomers discovered the youngest known hot Jupiter. The team observed the star for a month and a half and detected a regular fluctuation in the star’s velocity, revealing the presence of a planet almost as massive as Jupiter, orbiting its host star at a distance only one twentieth of that between the Earth and the Sun. The discovery shows for the first time that hot Jupiters can appear at a very early stage in the formation of planetary systems, and therefore have a major impact on their architecture.

In the Solar System, small rocky planets such as the Earth orbit near the Sun, whereas gas giants like Jupiter and Saturn are found much further out. Astronomers were therefore astonished when the first exoplanets detected turned out to be giants orbiting close to their host star. Theoretical work indicates that such planets can only form in the icy outer regions of the protoplanetary disk in which both the central star and its surrounding planets are born. Some, however, migrate inwards and yet avoid falling into their host star, thus becoming hot Jupiters.

Theoretical models predict that migration occurs either early in the lives of giant planets while still embedded within the protoplanetary disk, or else much later, once multiple planets are formed and interact, flinging some of them into the immediate vicinity of their star. Among the known hot Jupiters, some feature tilted or even backward orbits, suggesting that they were hurled towards their star by neighboring bodies. The discovery of a very young hot Jupiter thus confirms that early migration within the disk also applies to giant planets.

Detecting planets in orbit around very young stars proves to be a significant observational challenge, since such stars are monsters in comparison with our own Sun. This is because their intense magnetic activity interferes with the light emitted by the star to a far greater extent than a potential giant planet, even in a close orbit. One of the team’s achievements was to separate the signal caused by the star’s activity from the signal produced by the planet.

For this discovery, the team used the twin spectropolarimeters[4] ESPaDOnS and Narval, designed and built at IRAP. ESPaDOnS is mounted on the Canada-France-Hawaii Telescope (CFHT) on the summit of Maunakea, a dormant volcano on the Island of Hawaii. Narval is mounted on the Bernard Lyot telescope (TBL — OMP) atop the Pic du Midi in the French Pyrenees. The combined use of these two telescopes together with Hawaii’s Gemini telescope was essential for the required continuous monitoring of V830 Tau. SPIRou and SPIP, the next-generation infrared spectropolarimeters built at IRAP for the CFHT and TBL, scheduled for first light in 2017 and 2019 respectively, will offer vastly superior performance and make it possible to study the formation of new worlds with unprecedented sensitivity.