Date:
March 30, 2017

Source:
Princeton University

Summary:
The part of the brain that creates mental maps of one’s environment plays a much broader role in memory and learning than was previously thought, according to new research.

 

Rats were trained to depress a lever and then release it when the sound reached a certain frequency.
Credit: Illustration by Julia Kuhl

 

 

The part of the brain that creates mental maps of one’s environment plays a much broader role in memory and learning than was previously thought, according to new research published this week in the journal Nature by researchers at Princeton University.

“Almost 40 years of research suggested that a certain region of the brain was devoted to spatial navigation,” said David Tank, Princeton’s Henry L. Hillman Professor in Molecular Biology and co-director of the Princeton Neuroscience Institute. “We found that this same region is also involved when navigating not only spatial environments but also cognitive ones.”

The study looked at a region of the brain called the hippocampus that has been known since the 1970s to become active when rats travel around their environments. That research, and related work showing that cells in the nearby entorhinal cortex fire when animals reach specific locations, led to the finding that the brain creates an internal representation of the outside world — a sort of mental positioning system — that tells an animal where it is in its environment. These findings earned three scientists the 2014 Nobel Prize in Physiology or Medicine.

Now researchers at Princeton have found that those same brain regions are active when the brain is exploring a very different kind of environment, one involving listening to sounds. The researchers monitored neural activity as the rats listened and responded to certain sounds, and found similar firing patterns to those seen when rats are exploring their environments.

The research addresses a longstanding mystery in neuroscience, how the hippocampus could be associated both with making maps of the external environment and with making new memories. People with damage to the hippocampus, such as the amnesia patient known by the initials H.M. who participated in five decades of studies until his death in 2008, lack the ability to form new memories.

In previous studies where scientists monitored the electrical activity of cells in the hippocampus, they found that the cells fired in sequences that represented where the animal was, which direction its head was facing, which direction it was traveling and where it was relative to a boundary, according to Dmitriy Aronov, first author on the paper who conducted the work while a postdoctoral researcher at the Princeton Neuroscience Institute and who is now an assistant professor of neuroscience at Columbia University. “The mystery was, what do these firing patterns have to do with memory?”

The researchers theorized that perhaps the hippocampus and the nearby entorhinal cortex, which work together to make these mental maps, were in fact not specific to mapping per se but were involved in more general cognitive tasks, and that mapping was just one aspect of larger cognitive tasks involving learning and memory. Perhaps the reason previous studies only turned up the location-finding tasks is because rats spend most of their time exploring their environments as they forage for food.

By giving the rats a different task, such as exploring sounds, the researchers might see evidence of cognitive activities in the hippocampal-entorhinal circuit. The researchers chose sound as an analogy to space because both can vary along a continuum: the rats can explore ever-increasing frequencies the way they would move forward along a lengthy corridor.

To test the theory, the researchers monitored the electrical activity of neurons in the hippocampal and entorhinal regions while the rats manipulated sounds and learned to associate certain sound frequencies with rewards. Tank and Aronov teamed with undergraduate Rhino Nevers, Class of 2018, to conduct the work. The researchers first taught the rats to depress a lever to increase the pitch, or frequency, of a tone being played over a speaker. The rats learned that if they released the lever when the tone reached a predetermined frequency range, they would receive a reward.

The team observed that the patterns of neuronal firing corresponded to the rats’ behaviors during the task. Sequences of neural activity were produced as the rats advanced through the progression of frequencies, analogous to the sequences produced during traversing a progression of places in space. There were even patterns that corresponded to particular sound frequencies. The neurons involved in these firing patterns were identical to those involved in mapping and navigation. These cells included hippocampal place cells, so named because they fire when the rat is in a particular place, and entorhinal grid cells, which fire when the rats pass through certain locations.

The findings suggest that there are common mechanisms in the hippocampal-entorhinal system that can represent diverse sorts of tasks, said Tank, who is also director of the Simons Collaboration on the Global Brain. “The implication from our work is that these brain areas don’t represent location specifically, but rather they can represent other relevant features of the animal’s experience. When those features vary in a continuous way, sequences of neural activation are produced,” Tank said.

The discovery fits with how we think about mapping our environment in the context of learning about new places and forming memories of experiences, said Aronov. “When you visit a new location, you don’t only make a mental map, but you also form memories of your location. We feel that this study solves the mystery of the hippocampus in representing both memory and location, in that these neurons are general purpose neurons capable of representing any relevant information.”


Story Source:

Materials provided by Princeton University. Note: Content may be edited for style and length.


Journal Reference:

  1. Dmitriy Aronov, Rhino Nevers, David W. Tank. Mapping of a non-spatial dimension by the hippocampal–entorhinal circuit. Nature, 2017; 543 (7647): 719 DOI: 10.1038/nature21692

 

Source: Princeton University. “Brain’s ‘GPS’ does a lot more than just navigate.” ScienceDaily. ScienceDaily, 30 March 2017. <www.sciencedaily.com/releases/2017/03/170330115157.htm>.

Date:
March 27, 2017

Source:
New York University

Summary:
Brain size in primates is predicted by diet, an analysis by a team of anthropologists indicates. These results call into question “the social brain hypothesis,” which has posited that humans and other primates are big-brained due to factors pertaining to sociality.

 

Brain size in primates is predicted by diet, an analysis by a team of NYU anthropologists indicates. Above, a chimpanzee eating fruit.
Credit: James Higham

 

 

Brain size in primates is predicted by diet, an analysis by a team of New York University anthropologists indicates. These results call into question “the social brain hypothesis,” which has posited that humans and other primates are big-brained due to factors pertaining to sociality.

The findings, which appear in the journal Nature Ecology and Evolution, reinforce the notion that both human and non-human primate brain evolution may be driven by differences in feeding rather than in socialization.

“Are humans and other primates big-brained because of social pressures and the need to think about and track our social relationships, as some have argued?” asks James Higham, an assistant professor in NYU’s Department of Anthropology and a co-author of the new analysis. “This has come to be the prevailing view, but our findings do not support it — in fact, our research points to other factors, namely diet.”

“Complex foraging strategies, social structures, and cognitive abilities, are likely to have co-evolved throughout primate evolution,” adds Alex DeCasien, an NYU doctoral candidate and lead author of the study. “However, if the question is: ‘Which factor, diet or sociality, is more important when it comes to determining the brain size of primate species?’ then our new examination suggests that factor is diet.”

The social brain hypothesis sees social complexity as the primary driver of primate cognitive complexity, suggesting that social pressures ultimately led to the evolution of the large human brain. While some studies have shown positive relationships between relative brain size and group size, other studies which examined the effects of different social or mating systems have revealed highly conflicting results, raising questions about the strength of the social brain hypothesis.

In the Nature Ecology and Evolution study, the researchers, who also included Scott Williams, an assistant professor of anthropology at NYU, examined more than 140 primate species — or more than three times as many as previous studies — and incorporated more recent evolutionary trees, or phylogenies. They took into account food consumption across the studied species — folivores (leaves), frugivores (fruit), frugivores/folivores, and omnivores (addition of animal protein) — as well as several measures of sociality, such as group size, social system, and mating system.

Their results showed that brain size is predicted by diet rather than by the various measures of sociality — after controlling for body size and phylogeny. Notably, frugivores and frugivore/folivores exhibit significantly larger brains than folivores and, to a lesser extent, omnivores show significantly larger brains than folivores.

The researchers caution that the results do not reveal an association between brain size and fruit or protein consumption on a within-species level; rather, they note, they are evidence of the cognitive demands required by different species to obtain certain foods.

“Fruit is patchier in space and time in the environment, and the consumption of it often involves extraction from difficult-to-reach-places or protective skins,” observes DeCasien. “Together, these factors may lead to the need for relatively greater cognitive complexity and flexibility in frugivorous species.”


Story Source:

Materials provided by New York University. Note: Content may be edited for style and length.


Journal Reference:

  1. Alex R. DeCasien, Scott A. Williams, James P. Higham. Primate brain size is predicted by diet but not sociality. Nature Ecology & Evolution, 2017; 1: 0112 DOI: 10.1038/s41559-017-0112

 

Source: New York University. “Why are primates big-brained? Researchers’ answer is food for thought.” ScienceDaily. ScienceDaily, 27 March 2017. <www.sciencedaily.com/releases/2017/03/170327114719.htm>.

Date:
March 28, 2017

Source:
Brown University

Summary:
A young-looking volcanic caldera on the Moon has been interpreted by some as evidence of relatively recent lunar volcanic activity, but new research suggests it’s not so young after all.

 

The feature known as Ina, as seen by NASA’s Lunar Reconnaissance Orbiter, was likely formed by an eruption of fluffy ‘magmatic foam,’ new research shows.
Credit: NASA/GSFC/ASU

 

 

While orbiting the Moon in 1971, the crew of Apollo 15 photographed a strange geological feature — a bumpy, D-shaped depression about two miles long and a mile wide — that has fascinated planetary scientists ever since. Some have suggested that the feature, known as Ina, is evidence of a volcanic eruption Moon within the past 100 million years — a billion years or so after most volcanic activity on the Moon is thought to have ceased.

But new research led by Brown University geologists suggests that Ina is not so young after all. The analysis, published in the journal Geology, concludes that the feature was actually formed by an eruption around 3.5 billion years ago, around the same age as the dark volcanic deposits we see on the Moon’s nearside. It’s the peculiar type of lava that erupted from Ina that helps hide its age, the researchers say.

“As interesting as it would be for Ina to have formed in the recent geologic past, we just don’t think that’s the case,” said Jim Head, co-author of the paper and professor in Brown’s Department of Earth, Environmental and Planetary Sciences. “The model we’ve developed for Ina’s formation puts it firmly within the period of peak volcanic activity on the Moon several billion years ago.”

Youthful appearance

Ina sits near the summit of a gently sloped mound of basaltic rock, leading many scientists to conclude that it was likely the caldera of an ancient lunar volcano. But just how ancient wasn’t clear. While the flanks of the volcano look billions of years old, the Ina caldera itself looks much younger. One sign of youth is its bright appearance relative to its surroundings. The brightness suggests Ina hasn’t had time to accumulate as much regolith, the layer of loose rock and dust that builds up on the surface over time.

Then there are Ina’s distinctive mounds — 80 or so smooth hills of rock, some standing as tall as 100 feet, which dominate the landscape within the caldera. The mounds appear to have far fewer impact craters on them compared to the surrounding area, another sign of relative youth. Over time, it’s expected that a surface should accumulate craters of various sizes at fairly constant rates. So scientists use the number and size of craters to estimate the relative age of a surface. In 2014, a team of researchers did a careful crater-count on Ina’s mounds and concluded that they must have been formed by lava that erupted to the surface within the last 50 to 100 million years.

“That was a really puzzling finding,” Head said. “I think most people agree that the volcano Ina sits on was formed billions of years ago, which means there would have been a pause in volcanic activity for a billion years or more before the activity that formed Ina. We wanted to see if there might be something about geologic structure within Ina that throws off our estimation of its age.”

Not so young?

The researchers looked at well-studied volcanoes on Earth that might be similar to Ina. Ina appears to be a pit crater on a shield volcano, a gently sloping mountain similar to the Kilauea volcano in Hawaii. Kilauea has a pit crater similar to Ina known as the Kilauea Iki crater, which erupted in 1959.

As lava from that eruption solidified, it created a highly porous rock layer inside the pit, with underground vesicles as large as three feet in diameter and surface void space as deep as two feet. That porous surface, Head and his colleagues say, is created by the nature of the lava erupted in the late stages of events like this one. As the subsurface lava supply starts to diminish, it erupts as “magmatic foam” — a bubbly mixture of lava and gas. When that foam cools and solidifies, it forms the highly porous surface.

The researchers suggest that an Ina eruption would have also produced magmatic foam. And because of the Moon’s decreased gravity and nearly absent atmosphere, the lunar foam would have been even fluffier than on Earth, so it’s expected that the structures within Ina are even more porous than on Earth.

It’s the high porosity of those surfaces that throws off date estimates for Ina, both by hiding the buildup of regolith and by throwing off crater counts.

A highly porous surface, the researchers say, would allow loose rock and dust to filter into surface void space, making it appear as though less regolith has built up. That process would be perpetuated by seismic shaking in the region, much of which is caused by ongoing meteor impacts. “It’s like banging on the side of a sieve to make the flour go through,” Head said. “Regolith is jostled into holes rather than sitting on the surface, which makes Ina look a lot younger.”

Porosity could also skew crater counts. Laboratory experiments using a high-speed projectile cannon have shown that impacts into porous targets make much smaller craters. Because of Ina’s extreme porosity, the researchers say, its craters are much smaller than they would normally be, and many craters might not be visible at all. That could drastically alter the age estimate derived from crater counts.

The researchers estimate that the porous surface would reduce by a factor of three the size of craters on Ina’s mounds. In other words, an impactor that would make a 100-foot-diameter crater in lunar basalt bedrock would make a crater of a little over 30 feet in a foam deposit. Taking that scaling relationship into account, the team gets a revised age for the Ina mounds of about 3.5 billion year old. That’s similar to the surface age of the volcanic shield that surrounds Ina, and places the Ina activity within the timeframe of common volcanism on the Moon.

The researchers believe this work offers a plausible explanation for Ina’s formation without having to invoke the puzzling billion-year pause in volcanic activity.

“We think the young-looking features in Ina are the natural consequence of magmatic foam eruptions on the Moon,” Head said. “These landforms created by these foams simply look a lot younger than they are.”


Story Source:

Materials provided by Brown University. Note: Content may be edited for style and length.


Journal Reference:

  1. Le Qiao, James Head, Lionel Wilson, Long Xiao, Mikhail Kreslavsky, Josef Dufek. Ina pit crater on the Moon: Extrusion of waning-stage lava lake magmatic foam results in extremely young crater retention ages. Geology, 2017; G38594.1 DOI: 10.1130/G38594.1

 

Source: Brown University. “How a young-looking lunar volcano hides its true age.” ScienceDaily. ScienceDaily, 28 March 2017. <www.sciencedaily.com/releases/2017/03/170328145323.htm>.

Date:
March 27, 2017

Source:
Penn State

Summary:
Unprecedented summer warmth and flooding, forest fires, drought and torrential rain — extreme weather events are occurring more and more often, but now an international team of climate scientists has found a connection between many extreme weather events and the impact climate change is having on the jet stream.

 

On the left is an image of the global circulation pattern on a normal day. On the right is the image of the global circulation pattern when extreme weather occurs. The pattern on the right shows extreme patterns of wind speeds going north and south, while the normal pattern on the left shows moderate speed winds in both the north and south directions.
Credit: Michael Mann / Penn State

 

 

Unprecedented summer warmth and flooding, forest fires, drought and torrential rain — extreme weather events are occurring more and more often, but now an international team of climate scientists has found a connection between many extreme weather events and the impact climate change is having on the jet stream.

“We came as close as one can to demonstrating a direct link between climate change and a large family of extreme recent weather events,” said Michael Mann, distinguished professor of atmospheric science and director, Earth System Science Center, Penn State. “Short of actually identifying the events in the climate models.”

The unusual weather events that piqued the researchers’ interest are things such as the 2003 European heat wave, the 2010 Pakistan flood and Russian heatwave, the 2011 Texas and Oklahoma heat wave and drought and the 2015 California wildfires.

The researchers looked at a combination of roughly 50 climate models from around the world that are part of the Coupled Model Intercomparison Project Phase 5 (CMIP5), which is part of the World Climate Research Programme. These models are run using specific scenarios and producing simulated data that can be evaluated across the different models. However, while the models are useful for examining large-scale climate patterns and how they are likely to evolve over time, they cannot be relied on for an accurate depiction of extreme weather events. That is where actual observations prove critical.

The researchers looked at the historical atmospheric observations to document the conditions under which extreme weather patterns form and persist. These conditions occur when the jet stream, a global atmospheric wave of air that encompasses the Earth, becomes stationary and the peaks and troughs remain locked in place.

“Most stationary jet stream disturbances, however, will dissipate over time,” said Mann. “Under certain circumstances the wave disturbance is effectively constrained by an atmospheric wave guide, something similar to the way a coaxial cable guides a television signal. Disturbances then cannot easily dissipate, and very large amplitude swings in the jet stream north and south can remain in place as it rounds the globe.”

This constrained configuration of the jet stream is like a rollercoaster with high peaks and valleys, but only forms when there are six, seven or eight pairs of peaks and valleys surrounding the globe. The jet stream can then behave as if there is a waveguide — uncrossable barriers in the north and south — and a wave with large peaks and valleys can occur.

“If the same weather persists for weeks on end in one region, then sunny days can turn into a serious heat wave and drought, and lasting rains can lead to flooding,” said Stefan Rahmstorf, Potsdam Institute for Climate Impact Research (PIK), Germany.

The structure of the jet stream relates to its latitude and the temperature gradient from north to south.

Temperatures typically have the steepest gradients in mid-latitudes and a strong circumpolar jet stream arises. However, when these temperature gradients decrease in just the right way, a weakened “double peak” jet stream arises with the strongest jet stream winds located to the north and south of the mid-latitudes.

“The warming of the Arctic, the polar amplification of warming, plays a key role here,” said Mann. “The surface and lower atmosphere are warming more in the Arctic than anywhere else on the globe. That pattern projects onto the very temperature gradient profile that we identify as supporting atmospheric waveguide conditions.”

Theoretically, standing jet stream waves with large amplitude north/south undulations should cause unusual weather events.

“We don’t trust climate models yet to predict specific episodes of extreme weather because the models are too coarse,” said study co-author Dim Coumou of PIK. “However, the models do faithfully reproduce large scale patterns of temperature change,” added co-author Kai Kornhuber of PIK.

The researchers looked at real-world observations and confirmed that this temperature pattern does correspond with the double-peaked jet stream and waveguide patter associated with persistent extreme weather events in the late spring and summer such as droughts, floods and heat waves. They found the pattern has become more prominent in both observations and climate model simulations.

“Using the simulations, we demonstrate that rising greenhouse gases are responsible for the increase,” said Mann. The researchers noted in today’s (Mar. 27) issue of Scientific Reports that “Both the models and observations suggest this signal has only recently emerged from the background noise of natural variability.”

“We are now able to connect the dots when it comes to human-caused global warming and an array of extreme recent weather events,” said Mann.

While the models do not reliably track individual extreme weather events, they do reproduce the jet stream patterns and temperature scenarios that in the real world lead to torrential rain for days, weeks of broiling sun and absence of precipitation.

“Currently we have only looked at historical simulations,” said Mann. “What’s up next is to examine the model projections of the future and see what they imply about what might be in store as far as further increases in extreme weather are concerned.”

Also working on this project was Sonya K. Miller, programmer analyst, Penn State; and Byron A. Steinman, assistant professor Department of Earth and Environmental Sciences and Large Lakes Observatory, University of Minnesota: Duluth.


Story Source:

Materials provided by Penn State. Original written by A’ndrea Elyse Messer. Note: Content may be edited for style and length.


Journal Reference:

  1. Michael E. Mann, Stefan Rahmstorf, Kai Kornhuber, Byron A. Steinman, Sonya K. Miller, Dim Coumou. Influence of Anthropogenic Climate Change on Planetary Wave Resonance and Extreme Weather Events. Scientific Reports, 2017; 7: 45242 DOI: 10.1038/srep45242

 

Source: Penn State. “Extreme weather events linked to climate change impact on the jet stream.” ScienceDaily. ScienceDaily, 27 March 2017. <www.sciencedaily.com/releases/2017/03/170327083120.htm>.

Date:
March 27, 2017

Source:
NASA/Goddard Space Flight Center

Summary:
NASA’s Van Allen Probes uncover new phenomena in our near-Earth environment with their unique double orbit. Recently, the spacecraft were in just the right place, at just the right time, to catch an event caused by the fallout of a geomagnetic storm as it happened.

 

The twin Van Allen Probes orbit one behind the other, investigating clues in a way a single spacecraft never could. In this model, the trailing spacecraft saw an increase in injected oxygen particles (blue), which was unobserved by the first. The increase in particles was due to a geomagnetic storm front that moved across the path of the orbit after the first spacecraft passed.
Credit: NASA’s Goddard Space Flight Center/Mike Henderson/Joy Ng, Producer

 

 

High above Earth, two giant rings of energetic particles trapped by the planet’s magnetic field create a dynamic and harsh environment that holds many mysteries — and can affect spacecraft traveling around Earth. NASA’s Van Allen Probes act as space detectives, to help study the complex particle interactions that occur in these rings, known as the Van Allen radiation belts. Recently, the spacecraft were in just the right place, at just the right time, to catch an event caused by the fallout of a geomagnetic storm as it happened. They spotted a sudden rise in particles zooming in from the far side of the planet, improving our understanding of how particles travel in near-Earth space.

The two twin Van Allen Probe spacecraft orbit one behind the other, investigating clues in a way a single spacecraft never could. On one typical day, as the first instrument traveled around Earth, it spotted nothing unusual, but the second, following just an hour later, observed an increase in oxygen particles speeding around Earth’s dayside — the side nearest the sun. Where did these particles come from? How had they become so energized?

Scientists scoured the clues to figure out what was happening. With the help of computer models, they deduced that the particles had originated on the night side of Earth before being energized and accelerated through interactions with Earth’s magnetic field. As the particles journeyed around Earth, the lighter hydrogen particles were lost in collisions with the atmosphere, leaving an oxygen-rich plasma. The findings were presented in a recent paper in Geophysical Review Letters.

The unique double observations of the Van Allen Probes help untangle the complex workings of Earth’s magnetic environment. Such information has provided the very first view of these harsh belts from the inside — and it helps us better protect satellites and astronauts traveling through the region.


Story Source:

Materials provided by NASA/Goddard Space Flight Center. Note: Content may be edited for style and length.


Journal Reference:

  1. M. H. Denton, G. D. Reeves, M. F. Thomsen, M. G. Henderson, R. H. W. Friedel, B. Larsen, R. M. Skoug, H. O. Funsten, H. E. Spence, C. A. Kletzing. The complex nature of storm-time ion dynamics: Transport and local acceleration. Geophysical Research Letters, 2016; 43 (19): 10,059 DOI: 10.1002/2016GL070878

 

Source: NASA/Goddard Space Flight Center. “NASA spacecraft investigate clues in radiation belts.” ScienceDaily. ScienceDaily, 27 March 2017. <www.sciencedaily.com/releases/2017/03/170327114252.htm>.

Date:
March 23, 2017

Source:
Technical University of Munich (TUM)

Summary:
Scientists have developed a new method that can be used to construct custom hybrid structures using DNA and proteins. The method opens new opportunities for fundamental research in cell biology and for applications in biotechnology and medicine.

 

Desoxyribonucleic acid, better known by its abbreviation DNA, carries our genetic information. But to Prof. Hendrik Dietz and Florian Praetorius from TUM, DNA is also an excellent building material for nanostructures. Folding DNA to create three-dimensional shapes using a technique known as “DNA origami” is a long-established method in this context.
Credit: © MG / Fotolia

 

 

Florian Praetorius and Prof. Hendrik Dietz of the Technical University of Munich (TUM) have developed a new method that can be used to construct custom hybrid structures using DNA and proteins. The method opens new opportunities for fundamental research in cell biology and for applications in biotechnology and medicine.

Desoxyribonucleic acid, better known by its abbreviation DNA, carries our genetic information. But to Prof. Hendrik Dietz and Florian Praetorius from TUM, DNA is also an excellent building material for nanostructures. Folding DNA to create three-dimensional shapes using a technique known as “DNA origami” is a long-established method in this context.

But there are limits to this approach, explains Dietz. The “construction work” always takes place outside of biological systems and many components must be chemically synthesized. “Creating user-defined structures in sizes on the order of 10 to 100 nanometers inside a cell remains a great challenge,” he adds. Their newly developed technique now allows the researchers to use proteins to fold double-stranded DNA into desired three-dimensional shapes. Here, both the DNA and the required proteins can be genetically encoded and produced inside cells.

Proteins act as staples

Designed “staple proteins” based on TAL effectors are the key to the method. TAL effectors are produced in nature by certain bacteria that infect plants and are able to bind to specific sequences in the plant DNA, thereby neutralizing the plant’s defense mechanisms. “We’ve constructed variants of the TAL proteins which simultaneously recognize two custom target sequences at different sites in the DNA and then basically staple them together,” says Dietz. “This was exactly the property we needed: proteins that can staple DNA together.”

The second component of the system is a DNA double strand containing multiple binding sequences that can be recognized and linked by a set of different staple proteins. “In the simplest case a loop can be created by binding two points to one another,” Praetorius explains. “When several of these binding sites exist in the DNA, it’s possible to build more complex shapes.” An essential aspect of the researcher’s work was therefore determining a set of rules for arranging the staple proteins themselves and how to distribute the binding sequences on the DNA double strand in order to create the desired form.

New tools for fundamental research

What’s more, the staple proteins serve as anchor points for additional proteins: A method referred to as genetic fusion can be used to attach any functional protein domain desired. The hybrid structures made of DNA and proteins then function as a three-dimensional framework which can put the other protein domains into a particular spatial position. All the building blocks for the DNA protein hybrid structures can be produced by the cell itself and then assemble themselves autonomously. The researchers were able to produce the hybrids in environments resembling cells starting from genetic information. “There is a fairly high probability that this will also work in actual cells,” says Dietz.

The new method paves the way for controlling the spatial arrangement of molecules in living systems, which allows probing fundamental processes. For example, it’s assumed that the spatial arrangement of the genome has a substantial influence on which genes can be read and how efficient the reading process is. The intentional creation of loops using TAL-DNA hybrid structures in genomic DNA may provide a tool for investigating such processes.

It would also be possible to geometrically position a series of proteins inside and outside the cell in custom ways in order to investigate the influence of spatial proximity for example on information processing in the cell. The spatial proximity of certain enzymes could also make processes in biotechnology more efficient. Lastly, it would also be conceivable to utilize protein-DNA hybrid structures for example to better stimulate the immune response of cells, which can depend on the precise geometrical arrangement of multiple antigens.


Story Source:

Materials provided by Technical University of Munich (TUM). Note: Content may be edited for style and length.


Journal Reference:

  1. F. Praetorius and H. Dietz. Self-assembly of genetically encoded DNA-protein hybrid nanoscale shapes. Science, 2017 DOI: 10.1126/science.aaf5488

 

Source: Technical University of Munich (TUM). “Designer proteins fold DNA: Biophysicists construct complex hybrid structures using DNA and proteins.” ScienceDaily. ScienceDaily, 23 March 2017. <www.sciencedaily.com/releases/2017/03/170323141326.htm>.

Cells in mouse lungs produce most blood platelets and can replenish blood-making cells in bone marrow, study shows

Date:
March 22, 2017

Source:
University of California – San Francisco

Summary:
Using video microscopy in the living mouse lung, scientists have revealed that the lungs play a previously unrecognized role in blood production.

 

Release of platelets in the lung vasculature.
Credit: Image courtesy of University of California – San Francisco

 

 

Using video microscopy in the living mouse lung, UC San Francisco scientists have revealed that the lungs play a previously unrecognized role in blood production. As reported online March 22, 2017 in Nature, the researchers found that the lungs produced more than half of the platelets — blood components required for the clotting that stanches bleeding — in the mouse circulation. In another surprise finding, the scientists also identified a previously unknown pool of blood stem cells capable of restoring blood production when the stem cells of the bone marrow, previously thought to be the principal site of blood production, are depleted.

“This finding definitely suggests a more sophisticated view of the lungs — that they’re not just for respiration but also a key partner in formation of crucial aspects of the blood,” said pulmonologist Mark R. Looney, MD, a professor of medicine and of laboratory medicine at UCSF and the new paper’s senior author. “What we’ve observed here in mice strongly suggests the lung may play a key role in blood formation in humans as well.”

The findings could have major implications for understanding human diseases in which patients suffer from low platelet counts, or thrombocytopenia, which afflicts millions of people and increases the risk of dangerous uncontrolled bleeding. The findings also raise questions about how blood stem cells residing in the lungs may affect the recipients of lung transplants.

Mouse lungs produce more than 10 million platelets per hour, live imaging studies show

The new study was made possible by a refinement of a technique known as two-photon intravital imaging recently developed by Looney and co-author Matthew F. Krummel, PhD, a UCSF professor of pathology. This imaging approach allowed the researchers to perform the extremely delicate task of visualizing the behavior of individual cells within the tiny blood vessels of a living mouse lung.

Looney and his team were using this technique to examine interactions between the immune system and circulating platelets in the lungs, using a mouse strain engineered so that platelets emit bright green fluorescence, when they noticed a surprisingly large population of platelet-producing cells called megakaryocytes in the lung vasculature. Though megakaryocytes had been observed in the lung before, they were generally thought to live and produce platelets primarily in the bone marrow.

“When we discovered this massive population of megakaryocytes that appeared to be living in the lung, we realized we had to follow this up,” said Emma Lefrançais, PhD, a postdoctoral researcher in Looney’s lab and co-first author on the new paper.

More detailed imaging sessions soon revealed megakaryocytes in the act of producing more than 10 million platelets per hour within the lung vasculature, suggesting that more than half of a mouse’s total platelet production occurs in the lung, not the bone marrow, as researchers had long presumed. Video microscopy experiments also revealed a wide variety of previously overlooked megakaryocyte progenitor cells and blood stem cells sitting quietly outside the lung vasculature — estimated at 1 million per mouse lung.

Newly discovered blood stem cells in the lung can restore damaged bone marrow

The discovery of megakaryocytes and blood stem cells in the lung raised questions about how these cells move back and forth between the lung and bone marrow. To address these questions, the researchers conducted a clever set of lung transplant studies:

First, the team transplanted lungs from normal donor mice into recipient mice with fluorescent megakaryocytes, and found that fluorescent megakaryocytes from the recipient mice soon began turning up in the lung vasculature. This suggested that the platelet-producing megakaryocytes in the lung originate in the bone marrow.

“It’s fascinating that megakaryocytes travel all the way from the bone marrow to the lungs to produce platelets,” said Guadalupe Ortiz-Muñoz, PhD, also a postdoctoral researcher in the Looney lab and the paper’s other co-first author. “It’s possible that the lung is an ideal bioreactor for platelet production because of the mechanical force of the blood, or perhaps because of some molecular signaling we don’t yet know about.”

In another experiment, the researchers transplanted lungs with fluorescent megakaryocyte progenitor cells into mutant mice with low platelet counts. The transplants produced a large burst of fluorescent platelets that quickly restored normal levels, an effect that persisted over several months of observation — much longer than the lifespan of individual megakaryocytes or platelets. To the researchers, this indicated that resident megakaryocyte progenitor cells in the transplanted lungs had become activated by the recipient mouse’s low platelet counts and had produced healthy new megakaryocyte cells to restore proper platelet production.

Finally, the researchers transplanted healthy lungs in which all cells were fluorescently tagged into mutant mice whose bone marrow lacked normal blood stem cells. Analysis of the bone marrow of recipient mice showed that fluorescent cells originating from the transplanted lungs soon traveled to the damaged bone marrow and contributed to the production not just of platelets, but of a wide variety of blood cells, including immune cells such as neutrophils, B cells and T cells. These experiments suggest that the lungs play host to a wide variety of blood progenitor cells and stem cells capable of restocking damaged bone marrow and restoring production of many components of the blood.

“To our knowledge this is the first description of blood progenitors resident in the lung, and it raises a lot of questions with clinical relevance for the millions of people who suffer from thrombocytopenia,” said Looney, who is also an attending physician on UCSF’s pulmonary consult service and intensive care units.

In particular, the study suggests that researchers who have proposed treating platelet diseases with platelets produced from engineered megakaryocytes should look to the lungs as a resource for platelet production, Looney said. The study also presents new avenues of research for stem cell biologists to explore how the bone marrow and lung collaborate to produce a healthy blood system through the mutual exchange of stem cells.

“These observations alter existing paradigms regarding blood cell formation, lung biology and disease, and transplantation,” said pulmonologist Guy A. Zimmerman, MD, who is associate chair of the Department of Internal Medicine at the University of Utah School of Medicine and was an independent reviewer of the new study for Nature. “The findings have direct clinical relevance and provide a rich group of questions for future studies of platelet genesis and megakaryocyte function in lung inflammation and other inflammatory conditions, bleeding and thrombotic disorders, and transplantation.”

The observation that blood stem cells and progenitors seem to travel back and forth freely between the lung and bone marrow lends support to a growing sense among researchers that stem cells may be much more active than previously appreciated, Looney said. “We’re seeing more and more that the stem cells that produce the blood don’t just live in one place but travel around through the blood stream. Perhaps ‘studying abroad’ in different organs is a normal part of stem cell education.”


Story Source:

Materials provided by University of California – San Francisco. Original written by Nicholas Weiler. Note: Content may be edited for style and length.


Journal Reference:

  1. Emma Lefrançais, Guadalupe Ortiz-Muñoz, Axelle Caudrillier, Beñat Mallavia, Fengchun Liu, David M. Sayah, Emily E. Thornton, Mark B. Headley, Tovo David, Shaun R. Coughlin, Matthew F. Krummel, Andrew D. Leavitt, Emmanuelle Passegué, Mark R. Looney. The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors. Nature, 2017; DOI: 10.1038/nature21706

 

Source: University of California – San Francisco. “Surprising new role for lungs: Making blood: Cells in mouse lungs produce most blood platelets and can replenish blood-making cells in bone marrow, study shows.” ScienceDaily. ScienceDaily, 22 March 2017. <www.sciencedaily.com/releases/2017/03/170322143209.htm>.

Chicagoan receives stem cell transplant for CDA

Date:
March 20, 2017

Source:
University of Illinois at Chicago

Summary:
Using a technique that avoids the use of high-dose chemotherapy and radiation in preparation for a stem cell transplant, physicians have documented the first cure of an adult patient with congenital dyserythropoietic anemia.

 

David Levy, shown here with his sister, is the first adult patient cured of CDA.
Credit: David Levy

 

 

Using a technique that avoids the use of high-dose chemotherapy and radiation in preparation for a stem cell transplant, physicians at the University of Illinois Hospital & Health Sciences System have documented the first cure of an adult patient with congenital dyserythropoietic anemia. CDA is a rare blood disorder in which the body does not produce enough red blood cells, causing progressive organ damage and early death.

The transplant technique is unique, because it allows a donor’s cells to gradually take over a patient’s bone marrow without using toxic agents to eliminate a patient’s cells prior to the transplant.

Dr. Damiano Rondelli, the Michael Reese Professor of Hematology at the University of Illinois at Chicago, says the protocol can be used even in patients with a long history of disease and some organ damage because of the minimal use of chemotherapy.

“For many adult patients with a blood disorder, treatment options have been limited because they are often not sick enough to qualify for a risky procedure, or they are too sick to tolerate the toxic drugs used alongside a standard transplant,” said Rondelli, who is also division chief of hematology and oncology and director of the stem cell transplant program at UI Health.

“This procedure gives some adults the option of a stem cell transplant which was not previously available.”

For more than 30 years, Northbrook, Illinois, resident David Levy’s only course of treatment for CDA was regular blood transfusions to ensure his organs and tissues received enough oxygen. Levy was 24 when the pain became so severe he had to withdraw from graduate school.

“I spent the following years doing nothing — no work, no school, no social contact — because all I could focus on was managing my pain and getting my health back on track,” Levy said.

By age 32, Levy required transfusions every two to three weeks; had lost his spleen; had an enlarged liver; and was suffering severely from fatigue, heart palpitations and iron poisoning, a side effect of regular blood transfusions.

“It was bad,” Levy said. “I had been through enough pain. I was angry and depressed, and I wanted a cure. That’s why I started emailing Dr. Rondelli.”

Rondelli says that because of Levy’s range of illnesses and inability to tolerate chemotherapy and radiation, several institutions had denied him the possibility of a stem cell transplant. UI Health’s advances in curing sickle cell patients opened up a new possibility. Rondelli performed Levy’s transplant in 2014.

“The transplant was hard, and I had some complications, but I am back to normal now,” said Levy, now 35. “I still have some pain and some lingering issues from the years my condition was not properly managed, but I can be independent now. That is the most important thing to me.”

Levy is finishing his doctorate in psychology and running group therapy sessions at a behavioral health hospital.

Rondelli says the potential of this approach to stem cell transplantation is very promising.

“The use of this transplant protocol may represent a safe therapeutic strategy to treat adult patients with many types of congenital anemias — perhaps the only possible cure,” Rondelli said.

This case report is published in a letter to the editor in the journal Bone Marrow Transplantation.


Story Source:

Materials provided by University of Illinois at Chicago. Note: Content may be edited for style and length.


Journal Reference:

  1. A Oh, P R Patel, N Aardsma, S R Mehendale, R Chowdhery, K Sweiss, D Rondelli. Non-myeloablative allogeneic stem cell transplant with post-transplant cyclophosphamide cures the first adult patient with congenital dyserythropoietic anemia. Bone Marrow Transplantation, 2017; DOI: 10.1038/bmt.2017.17

 

Source: University of Illinois at Chicago. “First patient cured of rare blood disorder: Chicagoan receives stem cell transplant for CDA.” ScienceDaily. ScienceDaily, 20 March 2017. <www.sciencedaily.com/releases/2017/03/170320143831.htm>.

Date:
March 20, 2017

Source:
University of York

Summary:
Researchers have developed a mathematical formula based on the rhythmic movement of a sperm’s head and tail, which significantly reduces the complexities of understanding and predicting how sperm make the difficult journey towards fertilizing an egg.

 

The whip-like tail of the sperm has a particular rhythm that pulls the head backwards and sideways to create a jerky fluid flow.
Credit: Image courtesy of University of York

 

 

Researchers have developed a mathematical formula based on the rhythmic movement of a sperm’s head and tail, which significantly reduces the complexities of understanding and predicting how sperm make the difficult journey towards fertilizing an egg.

Researchers at the Universities of York, Birmingham, Oxford and Kyoto University, Japan, found that the sperm’s tail creates a characteristic rhythm that pushes the sperm forward, but also pulls the head backwards and sideways in a coordinated fashion.

Successful fertility relies on how a sperm moves through fluid, but capturing details of this movement is a complicated issue.

The team aim to use these new findings to understand how larger groups of sperm behave and interact, a task that would be impossible using modern observational techniques. The work could provide new insights into treating male infertility.

Dr Hermes Gadêlha, from the University of York’s Department of Mathematics, said: “In order to observe, at the microscale, how a sperm achieves forward propulsion through fluid, sophisticated microscopic high precision techniques are currently employed.

“Measurements of the beat of the sperm’s tail are fed into a computer model, which then helps to understand the fluid flow patterns that result from this movement.

“Numerical simulations are used to identify the flow around the sperm, but as the structures of the fluid are so complex, the data is particularly challenging to understand and use. Around 55 million spermatozoa are found in a given sample, so it is understandably very difficult to model how they move simultaneously.

“We wanted to create a mathematical formula that would simplify how we address this problem and make it easier to predict how large numbers of sperm swim. This would help us understand why some sperm succeed and others fail.”

By analysing the head and tail movements of the sperm, researchers have now shown that the sperm moves the fluid in a coordinated rhythmic way, which can be captured to form a relatively simple mathematical formula. This means complex and expensive computer simulations are no longer needed to understand how the fluid moves as the sperm swim.

The research demonstrated that the sperm has to make multiple contradictory movements, such as moving backwards, in order to propel it forward towards the egg.

The whip-like tail of the sperm has a particular rhythm that pulls the head backwards and sideways to create a jerky fluid flow, countering some of the intense friction that is created due to their diminutive sizes.

Dr Gadêlha said: “It is true when scientists say how miraculous it is that a sperm ever reaches an egg, but the human body has a very sophisticated system of making sure the right cells come together.

“You would assume that the jerky movements of the sperm would have a very random impact on the fluid flow around it, making it even more difficult for competing sperm cells to navigate through it, but in fact you see well defined patterns forming in the fluid around the sperm.

“This suggests that to achieve sperm stirs the fluid around in a very coordinated way locomotion, not too dissimilar to the way in which magnetic fields are formed around magnets. So although the fluid drag makes it very difficult for the sperm to make forward motion, it does coordinate with its rhythmic movements to ensure that only a few selected ones achieve forward propulsion.”

Now that the team has a mathematical formula that can predict the fluid movement of one sperm, the next step is to use the model for predictions on larger numbers of cells. They also believe that it will have implications for new innovations in infertility treatment.


Story Source:

Materials provided by University of York. Note: Content may be edited for style and length.


Journal Reference:

  1. Kenta Ishimoto, Hermes Gadêlha, Eamonn A. Gaffney, David J. Smith, and Jackson Kirkman-Brown. Coarse-graining the fluid flow around a human sperm. Physical Review Letters, March 2017

 

Source: University of York. “Mystery of how sperm swim revealed in mathematical formula.” ScienceDaily. ScienceDaily, 20 March 2017. <www.sciencedaily.com/releases/2017/03/170320085505.htm>.

Conference: eSource Data in Clinical Investigations – May 2-3, 2017 – Doubletree Center City, Philadelphia, Pa

 

Target Health Inc. is pleased to announce that Dr. Jules Mitchel will be presenting at CBI’s 4th Annual Bootcamp on eSource Data in Clinical Investigations. The conference aims to initiate meaningful dialogues, through collaborative sessions and investigative case studies, around early successes, challenges and failures, so that one can build an eSource adoption business case for senior leadership addressing balance of risk and cost.

 

Dr. Mitchel’s presentation is entitled: “The Future is Now: How  to Obtain Stakeholder Buy-in and Initiate the Migration to eSource.” In this case study, you will learn how eSource reduced monitoring and increased overall data quality, as well as how to convince stakeholders to invest in eSource. You will also learn of the current challenges of interoperability between EHR and eSource and what the long-term strategy looks like in moving away from EDC as we know it today.

 

Please Mention Promo Code: NCE547 for a $500 discount when you register at the conference www.cbinet.com/esource.

 

For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 165). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.

 

Joyce Hays, Founder and Editor in Chief of On Target

Jules Mitchel, Editor

 

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