Friday, May 31, 2019
When mitochondria become damaged, they avoid causing further problems by signaling cellular proteins to degrade them. In a paper publishing April 11, 2019, in the journal Developmental Cell, scientists in Norway report that they have discovered how the cells trigger this process, which is called mitophagy. In cells with broken mitochondria, two proteins — NIPSNAP 1 and NIPSNAP 2 — accumulate on the mitochondrial surface, functioning as “eat me” signals, recruiting the cellular machinery that will destroy them.
NIPSNAP 1 and 2 are normally found inside healthy mitochondria, although their function inside the cell is unknown. “When a cell’s respiration chain is disrupted, and the mitochondria are damaged, import of these proteins into the matrix and inner membrane space of the mitochondria is interrupted,” says senior author Anne Simonsen, a professor at the Department of Molecular Medicine at the Institute of Basic Medical Sciences of the University of Oslo. “In that case, the import system does not function and they remain bound to the surface of the damaged mitochondria signaling for mitophagy.”
In this study, the researchers studied human HeLa cells where both NIPSNAP1 and NIPSNAP 2 function were eliminated. “When we do that, these cells cannot clear the mitochondria after damage,” says Simonsen. However, in cells with functional NIPSNAP proteins, when mitophagy was induced through the addition of a chemical disruptor, they observed that the NIPSNAP proteins act in concert with the PINK and PARKIN proteins, proteins already known to have a role in triggering autophagy and to have a role in Parkinson’s Disease.
PARKIN labels cells with ubiquitin, a small protein that directs the cells towards degradation. “Ubiquitin is the classical signal to recruit autophagy,” says co-author Terje Johansen (@TerjeJohansen17), of the University of Tromsø — The Arctic University of Norway. “What we saw is that in addition to ubiquitin, NIPSNAP proteins are required to recruit autophagy proteins; they are not targeted to the mitochondria unless these NIPSNAP proteins are found on the surface.”
The team showed this finding has important physiological implications in vivo by investigating the NIPSNAP/PINK/PARKIN mechanism in a zebrafish animal model. They compared wild-type zebrafish and a fish line with reduced NIPSNAP1 protein abundance.
“We see that the mutant fish lacking adequate functional NIPSNAP1 are not able to move as the wild-type fish,” says Simonsen. They have a Parkinsonian-like phenotype with reduced numbers of dopaminergic neurons. However, they could rescue this locomotion defect by adding L-dopa, the same compound used to treat human Parkinson’s Disease, to the water.
Even more dramatically, animals entirely lacking NIPSNAP1 protein died within five days. “Clearly, clearance of mitochondria is important for the health of these dopaminergic neurons. That is particularly important since neurons generally cannot divide,” says Johansen.
As evolutionarily conserved proteins, NIPSNAP proteins are found throughout the animal kingdom, including humans.
Thursday, May 30, 2019
A gassy insulating layer beneath the icy surfaces of distant celestial objects could mean there are more oceans in the universe than previously thought.
Computer simulations provide compelling evidence that an insulating layer of gas hydrates could keep a subsurface ocean from freezing beneath Pluto’s icy exterior, according to a study published in the journal Nature Geoscience.
In July 2015, NASA’s New Horizons spacecraft flew through Pluto’s system, providing the first-ever close-up images of this distant dwarf planet and its moons. The images showed Pluto’s unexpected topography, including a white-colored ellipsoidal basin named Sputnik Planitia, located near the equator and roughly the size of Texas.
Because of its location and topography, scientists believe a subsurface ocean exists beneath the ice shell which is thinned at Sputnik Planitia. However, these observations are contradictory to the age of the dwarf planet because the ocean should have frozen a long time ago and the inner surface of the ice shell facing the ocean should have also been flattened.
Researchers at Japan’s Hokkaido University, the Tokyo Institute of Technology, Tokushima University, Osaka University, Kobe University, and at the University of California, Santa Cruz, considered what could keep the subsurface ocean warm while keeping the ice shell’s inner surface frozen and uneven on Pluto. The team hypothesized that an “insulating layer” of gas hydrates exists beneath the icy surface of Sputnik Planitia. Gas hydrates are crystalline ice-like solids formed of gas trapped within molecular water cages. They are highly viscous, have low thermal conductivity, and could therefore provide insulating properties.
The researchers conducted computer simulations covering a timescale of 4.6 billion years, when the solar system began to form. The simulations showed the thermal and structural evolution of Pluto’s interior and the time required for a subsurface ocean to freeze and for the icy shell covering it to become uniformly thick. They simulated two scenarios: one where an insulating layer of gas hydrates existed between the ocean and the icy shell, and one where it did not.
The simulations showed that, without a gas hydrate insulating layer, the subsurface sea would have frozen completely hundreds of millions of years ago; but with one, it hardly freezes at all. Also, it takes about one million years for a uniformly thick ice crust to completely form over the ocean, but with a gas hydrate insulating layer, it takes more than one billion years.
The simulation’s results support the possibility of a long-lived liquid ocean existing beneath the icy crust of Sputnik Planitia.
The team believes that the most likely gas within the hypothesized insulating layer is methane originating from Pluto’s rocky core. This theory, in which methane is trapped as a gas hydrate, is consistent with the unusual composition of Pluto’s atmosphere — methane-poor and nitrogen-rich.
Similar gas hydrate insulating layers could be maintaining long-lived subsurface oceans in other relatively large but minimally heated icy moons and distant celestial objects, the researchers conclude. “This could mean there are more oceans in the universe than previously thought, making the existence of extraterrestrial life more plausible,” says Shunichi Kamata of Hokkaido University who led the team.
Journal article: https://www.nature.com/articles/s41561-019-0369-8
Wednesday, May 29, 2019
NASA’s Mars Reconnaissance Orbiter hit a dizzying milestone: It completed 60,000 loops around the Red Planet. On average, MRO takes 112 minutes to circle Mars, whipping around at about 2 miles per second (3.4 kilometers per second).
Since entering orbit on March 10, 2006, the spacecraft has been collecting daily science about the planet’s surface and atmosphere, including detailed views with its High Resolution Imaging Science Experiment camera (HiRISE). HiRISE is powerful enough to see surface features the size of a dining room table from 186 miles (300 kilometers) above the surface.
Meanwhile, MRO is watching the daily weather and probing the subsurface for ice, providing data that can influence the designs of future missions that will take humans to Mars.
But MRO isn’t just sending back its own science; it serves in a network of relays that beam data back to Earth from NASA’s Mars rovers and landers. Later this month, MRO will hit another milestone: It will have relayed 1 terabit of data, largely from NASA’s Curiosity rover. If you’ve ever enjoyed one of Curiosity’s selfies or sprawling landscapes or wondered at its scientific discoveries, MRO probably helped make them possible.
MRO’s aerial perspective also provides scientists a complementary view of a dynamic planet. As seasons change, they can see avalanches and cloud patterns. HiRISE has imaged CO2 ice sublimating, migrating sand dunes and meteorite strikes reshaping the landscape. With its Mars Climate Sounder instrument and its Mars Color Imager camera, MRO can also study atmospheric events like the massive global dust storm that proved fatal to NASA’s Opportunity rover in 2018.
Source & further reading: https://www.nasa.gov/feature/jpl/nasas-mro-completes-60000-trips-around-mars
What if scientists could manipulate your brain so that a traumatic memory lost its emotional power over your psyche? Steve Ramirez, a Boston University neuroscientist fascinated by memory, believes that a small structure in the brain could hold the keys to future therapeutic techniques for treating depression, anxiety, and PTSD, someday allowing clinicians to enhance positive memories or suppress negative ones.
Inside our brains, a cashew-shaped structure called the hippocampus stores the sensory and emotional information that makes up memories, whether they be positive or negative ones. No two memories are exactly alike, and likewise, each memory we have is stored inside a unique combination of brain cells that contain all the environmental and emotional information associated with that memory. The hippocampus itself, although small, comprises many different subregions all working in tandem to recall the elements of a specific memory.
Now, in a new paper in Current Biology, Ramirez and a team of collaborators have shown just how pliable memory is if you know which regions of the hippocampus to stimulate — which could someday enable personalized treatment for people haunted by particularly troubling memories.
“Many psychiatric disorders, especially PTSD, are based on the idea that after there’s a really traumatic experience, the person isn’t able to move on because they recall their fear over and over again,” says Briana Chen, first author of the paper, who is currently a graduate researcher studying depression at Columbia University.
In their study, Chen and Ramirez, the paper’s senior author, show how traumatic memories — such as those at the root of disorders like PTSD — can become so emotionally loaded. By artificially activating memory cells in the bottom part of the brain’s hippocampus, negative memories can become even more debilitating. In contrast, stimulating memory cells in the top part of the hippocampus can strip bad memories of their emotional oomph, making them less traumatic to remember.
Well, at least if you’re a mouse.
Using a technique called optogenetics, Chen and Ramirez mapped out which cells in the hippocampus were being activated when male mice made new memories of positive, neutral, and negative experiences. A positive experience, for example, could be exposure to a female mouse. In contrast, a negative experience could be receiving a startling but mild electrical zap to the feet. Then, identifying which cells were part of the memory-making process (which they did with the help of a glowing green protein designed to literally light up when cells are activated), they were able to artificially trigger those specific memories again later, using laser light to activate the memory cells.
Their studies reveal just how different the roles of the top and bottom parts of the hippocampus are. Activating the top of the hippocampus seems to function like effective exposure therapy, deadening the trauma of reliving bad memories. But activating the bottom part of the hippocampus can impart lasting fear and anxiety-related behavioral changes, hinting that this part of the brain could be overactive when memories become so emotionally charged that they are debilitating.
That distinction, Ramirez says, is critical. He says that it suggests suppressing overactivity in the bottom part of the hippocampus could potentially be used to treat PTSD and anxiety disorders. It could also be the key to enhancing cognitive skills, “like Limitless,” he says, referencing the 2011 film starring Bradley Cooper in which the main character takes special pills that drastically improve his memory and brain function.
“The field of memory manipulation is still young…. It sounds like sci-fi but this study is a sneak preview of what’s to come in terms of our abilities to artificially enhance or suppress memories,” says Ramirez, a BU College of Arts & Sciences assistant professor of psychological and brain sciences. Although the study got its start while Chen and Ramirez were both doing research at Massachusetts Institute of Technology, its data has been the backbone of the first paper to come out of the new laboratory group that Ramirez established at BU in 2017.
“We’re a long way from being able to do this in humans, but the proof of concept is here,” Chen says. “As Steve likes to say, ‘never say never.’ Nothing is impossible.”
“This is the first step in teasing apart what these [brain] regions do to these really emotional memories…. The first step toward translating this to people, which is the holy grail,” says memory researcher Sheena Josselyn, a University of Toronto neuroscientist who was not involved in this study. “[Steve’s] group is really unique in trying to see how the brain stores memories with the goal being to help people… they’re not just playing around but doing it for a purpose.”
Although mouse brains and human brains are very different, Ramirez, who is also a member of the BU Center for Systems Neuroscience and the Center for Memory and Brain, says that learning how these fundamental principles play out in mice is helping his team map out a blueprint of how memory works in people. Being able to activate specific memories on demand, as well as targeted areas of the brain involved in memory, allows the researchers to see exactly what side effects come along with different areas of the brain being overstimulated.
“Let’s use what we’re learning in mice to make predictions about how memory functions in humans,” he says. “If we can create a two-way street to compare how memory works in mice and in humans, we can then ask specific questions [in mice] about how and why memories can have positive or negative effects on psychological health.”
Journal article: https://www.cell.com/current-biology/fulltext/S0960-9822(19)30494-4?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0960982219304944%3Fshowall%3Dtrue