Tuesday, 4 May 2021

Global glacier retreat has accelerated

Skaftafell glacier, Iceland 

 An international research team including scientists from ETH Zurich has shown that almost all the world's glaciers are becoming thinner and losing mass' and that these changes are picking up pace. The team's analysis is the most comprehensive and accurate of its kind to date.

Glaciers are a sensitive indicator of climate change -- and one that can be easily observed. Regardless of altitude or latitude, glaciers have been melting at a high rate since the mid-20th century. Until now, however, the full extent of ice loss has only been partially measured and understood. Now an international research team led by ETH Zurich and the University of Toulouse has authored a comprehensive study on global glacier retreat, which was published online in Nature on 28 April. This is the first study to include all the world's glaciers -- around 220,000 in total -- excluding the Greenland and Antarctic ice sheets. The study's spatial and temporal resolution is unprecedented -- and shows how rapidly glaciers have lost thickness and mass over the past two decades.

Rising sea levels and water scarcity What was once permanent ice has declined in volume almost everywhere around the globe. Between 2000 and 2019, the world's glaciers lost a total of 267 gigatonnes (billion tonnes) of ice per year on average -- an amount that could have submerged the entire surface area of Switzerland under six metres of water every year. The loss of glacial mass also accelerated sharply during this period. Between 2000 and 2004, glaciers lost 227 gigatonnes of ice per year, but between 2015 and 2019, the lost mass amounted to 298 gigatonnes annually. Glacial melt caused up to 21 percent of the observed rise in sea levels during this period -- some 0.74 millimetres a year. Nearly half of the rise in sea levels is attributable to the thermal expansion of water as it heats up, with meltwaters from the Greenland and Antarctic ice sheets and changes in terrestrial water storage accounting for the remaining third.

Among the fastest melting glaciers are those in Alaska, Iceland and the Alps. The situation is also having a profound effect on mountain glaciers in the Pamir mountains, the Hindu Kush and the Himalayas. "The situation in the Himalayas is particularly worrying," explains Romain Hugonnet, lead author of the study and researcher at ETH Zurich and the University of Toulouse. "During the dry season, glacial meltwater is an important source that feeds major waterways such as the Ganges, Brahmaputra and Indus rivers. Right now, this increased melting acts as a buffer for people living in the region, but if Himalayan glacier shrinkage keeps accelerating, populous countries like India and Bangladesh could face water or food shortages in a few decades." The findings of this study can improve hydrological models and be used to make more accurate predictions on a global and local scales -- for instance, to estimate how much Himalayan glacier meltwater one can anticipate over the next few decades.

To their surprise, the researchers also identified areas where melt rates slowed between 2000 and 2019, such as on Greenland's east coast and in Iceland and Scandinavia. They attribute this divergent pattern to a weather anomaly in the North Atlantic that caused higher precipitation and lower temperatures between 2010 and 2019, thereby slowing ice loss. The researchers also discovered that the phenomenon known as the Karakoram anomaly is disappearing. Prior to 2010, glaciers in the Karakoram mountain range were stable -- and in some cases, even growing. However, the researchers' analysis revealed that Karakoram glaciers are now losing mass as well.

Study based on stereo satellite images As a basis for the study, the research team used imagery captured on board NASA's Terra satellite, which has been orbiting the Earth once every 100 minutes since 1999 at an altitude of nearly 700 kilometres. Terra is home to ASTER, a multispectral imager with two cameras that record pairs of stereo images, allowing researchers to create high-resolution digital elevation models of all the world's glaciers. The team used the full archive of ASTER images to reconstruct a time series of glacial elevation, which enabled them to calculate changes in the thickness and mass of the ice over time.

Lead author Romain Hugonnet is a doctoral student at ETH Zurich and the University of Toulouse. He worked on this project for nearly three years and spent 18 months analysing the satellite data. To process the data, the researchers used a supercomputer at the University of Northern British Columbia. Their findings will be included in the next Assessment Report of the United Nations Intergovernmental Panel on Climate Change (IPCC), which is due to be published later this year. "Our findings are important on a political level. The world really needs to act now to prevent the worst-case climate change scenario," says co-author Daniel Farinotti, head of the glaciology group at ETH Zurich and the Swiss Federal Institute for Forest, Snow and Landscape Research WSL.

Friday, 5 March 2021

Origin of life: The chicken-and-egg problem

RNA abstract concept illustration 

A Ludwig-Maximilians-Universitaet (LMU) in Munich team has shown that slight alterations in transfer-RNA molecules (tRNAs) allow them to self-assemble into a functional unit that can replicate information exponentially. tRNAs are key elements in the evolution of early life-forms.

Life as we know it is based on a complex network of interactions, which take place at microscopic scales in biological cells, and involve thousands of distinct molecular species. In our bodies, one fundamental process is repeated countless times every day. In an operation known as replication, proteins duplicate the genetic information encoded in the DNA molecules stored in the cell nucleus -- before distributing them equally to the two daughter cells during cell division. The information is then selectively copied ('transcribed') into what are called messenger RNA molecules (mRNAs), which direct the synthesis of the many different proteins required by the cell type concerned. A second type of RNA -- transfer RNA (tRNA) -- plays a central role in the 'translation' of mRNAs into proteins. Transfer RNAs act as intermediaries between mRNAs and proteins: they ensure that the amino-acid subunits of which each particular protein consists are put together in the sequence specified by the corresponding mRNA.

How could such a complex interplay between DNA replication and the translation of mRNAs into proteins have arisen when living systems first evolved on the early Earth? We have here a classical example of the chicken-and-the-egg problem: Proteins are required for transcription of the genetic information, but their synthesis itself depends on transcription.

LMU physicists led by Professor Dieter Braun have now demonstrated how this conundrum could have been resolved. They have shown that minor modifications in the structures of modern tRNA molecules permit them to autonomously interact to form a kind of replication module, which is capable of exponentially replicating information. This finding implies that tRNAs -- the key intermediaries between transcription and translation in modern cells -- could also have been the crucial link between replication and translation in the earliest living systems. It could therefore provide a neat solution to the question of which came first -- genetic information or proteins?

Strikingly, in terms of their sequences and overall structure, tRNAs are highly conserved in all three domains of life, i.e. the unicellular Archaea and Bacteria (which lack a cell nucleus) and the Eukaryota (organisms whose cells contain a true nucleus). This fact in itself suggests that tRNAs are among the most ancient molecules in the biosphere.

Like the later steps in the evolution of life, the evolution of replication and translation -- and the complex relationship between them -- was not the result of a sudden single step. It is better understood as the culmination of an evolutionary journey. "Fundamental phenomena such as self-replication, autocatalysis, self-organization and compartmentalization are likely to have played important roles in these developments," says Dieter Braun. "And on a more general note, such physical and chemical processes are wholly dependent on the availability of environments that provide non-equilibrium conditions."

In their experiments, Braun and his colleagues used a set of reciprocally complementary DNA strands modeled on the characteristic form of modern tRNAs. Each was made up of two 'hairpins' (so called because each strand could partially pair with itself and form an elongated loop structure), separated by an informational sequence in the middle. Eight such strands can interact via complementary base-pairing to form a complex. Depending on the pairing patterns dictated by the central informational regions, this complex was able to encode a 4-digit binary code.

Each experiment began with a template -- an informational structure made up of two types of the central informational sequences that define a binary sequence. This sequence dictated the form of the complementary molecule with which it can interact in the pool of available strands. The researchers went on to demonstrate that the templated binary structure can be repeatedly copied, i.e. amplified, by applying a repeating sequence of temperature fluctuations between warm and cold. "It is therefore conceivable that such a replication mechanism could have taken place on a hydrothermal microsystem on the early Earth," says Braun. In particular, aqueous solutions trapped in porous rocks on the seafloor would have provided a favorable environment for such reaction cycles, since natural temperature oscillations, generated by convection currents, are known to occur in such settings.

During the copying process, complementary strands (drawn from the pool of molecules) pair up with the informational segment of the template strands. In the course of time, the adjacent hairpins of these strands also pair up to form a stable backbone, and temperature oscillations continue to drive the amplification process. If the temperature is increased for a brief period, the template strands are separated from the newly formed replicate, and both can then serve as template strands in the next round of replication.

The team was able to show that the system is capable of exponential replication. This is an important finding, as it shows that the replication mechanism is particularly resistant to collapse owing to the accumulation of errors. The fact that the structure of the replicator complex itself resembles that of modern tRNAs suggests that early forms of tRNA could have participated in molecular replication processes, before tRNA molecules assumed their modern role in the translation of messenger RNA sequences into proteins. "This link between replication and translation in an early evolutionary scenario could provide a solution to the chicken-and-the-egg problem," says Alexandra Kühnlein. It could also account for the characteristic form of proto-tRNAs, and elucidate the role of tRNAs before they were co-opted for use in translation.


 

Wednesday, 24 February 2021

Sleep is vital to associating emotion with memory, study finds

Woman sleeping

When you slip into sleep, it's easy to imagine that your brain shuts down, but University of Michigan research suggests that groups of neurons activated during prior learning keep humming, tattooing memories into your brain.

U-M researchers have been studying how memories associated with a specific sensory event are formed and stored in mice. In a study conducted prior to the coronavirus pandemic and recently published in Nature Communications, the researchers examined how a fearful memory formed in relation to a specific visual stimulus.

They found that not only did the neurons activated by the visual stimulus keep more active during subsequent sleep, sleep is vital to their ability to connect the fear memory to the sensory event.

Previous research has shown that regions of the brain that are highly active during intensive learning tend to show more activity during subsequent sleep. But what was unclear was whether this "reactivation" of memories during sleep needs to occur in order to fully store the memory of newly learned material.

"Part of what we wanted to understand was whether there is communication between parts of the brain that are mediating the fear memory and the specific neurons mediating the sensory memory that the fear is being tied to. How do they talk together, and must they do so during sleep? We would really like to know what's facilitating that process of making a new association, like a particular set of neurons, or a particular stage of sleep," said Sara Aton, senior author of the study and a professor in the U-M Department of Molecular, Cellular and Developmental Biology. "But for the longest time, there was really no way to test this experimentally."

Now, researchers have the tools to genetically tag cells that are activated by an experience during a specific window of time. Focusing on a specific set of neurons in the primary visual cortex, Aton and the study's lead author, graduate student Brittany Clawson, created a visual memory test. They showed a group of mice a neutral image, and expressed genes in the visual cortex neurons activated by the image.

To verify that these neurons registered the neutral image, Aton and her team tested whether they could instigate the memory of the image stimulus by selectively activating the neurons without showing them the image. When they activated the neurons and paired that activation with a mild foot shock, they found that their subjects would subsequently be afraid of visual stimuli that looked similar to the image those cells encode. They found the reverse also to be true: after pairing the visual stimulus with a foot shock, their subjects would subsequently respond with fear to reactivating the neurons.

"Basically, the precept of the visual stimulus and the precept of this completely artificial activation of the neurons generated the same response," Aton said.

The researchers found that when they disrupted sleep after they showed the subjects an image and had given them a mild foot shock, there was no fear associated with the visual stimulus. Those with unmanipulated sleep learned to fear the specific visual stimulus that had been paired with the foot shock.

"We found that these mice actually became afraid of every visual stimulus we showed them," Aton said. "From the time they go to the chamber where the visual stimuli are presented, they seem to know there's a reason to feel fear, but they don't know what specifically they're afraid of."

This likely shows that, in order for them to make an accurate fear association with a visual stimulus, they have to have sleep-associated reactivation of the neurons encoding that stimulus in the sensory cortex, according to Aton. This allows a memory specific to that visual cue to be generated.The researchers think that at the same time, that sensory cortical area must communicate with other brain structures, to marry the sensory aspect of the memory to the emotional aspect.


 

Tuesday, 16 February 2021

'Where did I park my car?' Brain stimulation improves mental time travel

Man trying to remember

You might remember you ate cereal for breakfast but forget the color of the bowl. Or recall watching your partner put the milk away but can't remember on which shelf.

A new Northwestern Medicine study improved memory of complex, realistic events similar to these by applying transcranial magnetic stimulation (TMS) to the brain network responsible for memory. The authors then had participants watch videos of realistic activities to measure how memory works during everyday tasks. The findings prove it is possible to measure and manipulate realistic types of memory.

"On a day-to-day basis we must remember complex events that involve many elements, such as different locations, people and objects," said lead author Melissa Hebscher, a postdoctoral fellow at Northwestern University Feinberg School of Medicine. "We were able to show that memory for complex, realistic events can be improved in a safe and non-invasive way using brain stimulation."

The study was conducted on healthy young adults in a controlled laboratory setting. These methods, however, also could eventually be used to improve memory in individuals with memory disorders due to brain damage or neurological disorders, Hebscher said.

The study will be published Feb. 4 in the journal Current Biology.

A new approach to studying memory: Incorporating video

The study authors used TMS with the goal of altering brain activity and memory for realistic events. Immediately following stimulation, subjects performed a memory task while having their brains scanned using functional magnetic resonance imaging (fMRI).

Instead of showing study participants pictures or lists of words -- typical practices in laboratory tests that analyze memory -- participants in this study watched videos of everyday activities such as such as someone folding laundry or taking out the garbage.

"Our study used video clips that more closely replicate how memory works on a day-to-day basis," Hebscher said.

Following stimulation, study participants more accurately answered questions about the content of the video clips, such as identifying the shirt color an actor was wearing or the presence of a tree in the background.

Additionally, the study found that brain stimulation led to higher quality reinstatement of memories in the brain. Reinstatement is when the brain replays or relives an original event, Hebscher said. Following stimulation, a person's brain activity while watching a video more closely resembled their brain activity when remembering that same video.

"This is why remembering can sometimes feel like 'mental time travel,'" Hebscher said. "Our findings show that stimulation enhances this 'mental time travel' in the brain and improves memory accuracy. These findings have implications for the development of safe and effective ways to improve real-world memory."


 

How a single gene alteration may have separated modern humans from predecessors

 

DNA illustration

As a professor of pediatrics and cellular and molecular medicine at University of California San Diego School of Medicine, Alysson R. Muotri, PhD, has long studied how the brain develops and what goes wrong in neurological disorders. For almost as long, he has also been curious about the evolution of the human brain -- what changed that makes us so different from preceding Neanderthals and Denisovans, our closest evolutionary relatives, now extinct?

Evolutionary studies rely heavily on two tools -- genetics and fossil analysis -- to explore how a species changes over time. But neither approach can reveal much about brain development and function because brains do not fossilize, Muotri said. There is no physical record to study.

So Muotri decided to try stem cells, a tool not often applied in evolutionary reconstructions. Stem cells, the self-renewing precursors of other cell types, can be used to build brain organoids -- "mini brains" in a laboratory dish. Muotri and colleagues have pioneered the use of stem cells to compare humans to other primates, such as chimpanzees and bonobos, but until now a comparison with extinct species was not thought possible.

In a study published February 11, 2021 in Science, Muotri's team catalogued the differences between the genomes of diverse modern human populations and the Neanderthals and Denisovans, who lived during the Pleistocene Epoch, approximately 2.6 million to 11,700 years ago. Mimicking an alteration they found in one gene, the researchers used stem cells to engineer "Neanderthal-ized" brain organoids.

"It's fascinating to see that a single base-pair alteration in human DNA can change how the brain is wired," said Muotri, senior author of the study and director of the UC San Diego Stem Cell Program and a member of the Sanford Consortium for Regenerative Medicine. "We don't know exactly how and when in our evolutionary history that change occurred. But it seems to be significant, and could help explain some of our modern capabilities in social behavior, language, adaptation, creativity and use of technology."

The team initially found 61 genes that differed between modern humans and our extinct relatives. One of these altered genes -- NOVA1 -- caught Muotri's attention because it's a master gene regulator, influencing many other genes during early brain development. The researchers used CRISPR gene editing to engineer modern human stem cells with the Neanderthal-like mutation in NOVA1. Then they coaxed the stem cells into forming brain cells and ultimately Neanderthal-ized brain organoids.

Brain organoids are little clusters of brain cells formed by stem cells, but they aren't exactly brains (for one, they lack connections to other organ systems, such as blood vessels). Yet organoids are useful models for studying genetics, disease development and responses to infections and therapeutic drugs. Muotri's team has even optimized the brain organoid-building process to achieve organized electrical oscillatory waves similar to those produced by the human brain.

The Neanderthal-ized brain organoids looked very different than modern human brain organoids, even to the naked eye. They had a distinctly different shape. Peering deeper, the team found that modern and Neanderthal-ized brain organoids also differ in the way their cells proliferate and how their synapses -- the connections between neurons -- form. Even the proteins involved in synapses differed. And electrical impulses displayed higher activity at earlier stages, but didn't synchronize in networks in Neanderthal-ized brain organoids.


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