Earth

Photosystem II is a protein complex in plants, algae and cyanobacteria that is responsible for splitting water and producing the oxygen we breathe. Over the past few years, an international collaboration between scientists at the Department of Energy's Lawrence Berkeley National Laboratory, SLAC National Accelerator Laboratory and several other institutions have been able to observe various steps of this water-splitting cycle at the temperature at which it occurs in nature.

Now, the team has used the same method to zero in on a key step in which a water molecule moves in to bridge manganese and calcium atoms in the catalytic complex that splits water to produce breathable oxygen. What they learned brings them one step closer to obtaining a complete picture of this natural process, which could inform the next generation of artificial photosynthetic systems that produce clean and renewable energy from sunlight and water. Their results were published in the Proceedings of the National Academy of Sciences today.

"We demonstrated that it is possible to make these measurements in previous iterations of this work, but we never had the spatial resolution or enough time points to really drill down into these finer details," says co-author Uwe Bergmann, a distinguished staff scientist at SLAC. "After carefully optimizing this experiment over many years, we honed our ability to make measurements at high enough quality to see these tiny changes for the first time."

The bucket brigade

During photosynthesis, the oxygen-evolving complex, a cluster of four manganese atoms and one calcium atom connected by oxygen atoms, cycles through four stable oxidation states, known as S0 through S3, when exposed to sunlight.

On a baseball field, S0 would be the start of the game when a player on home base is ready to go to bat. S1-S3 would be players on first, second, and third. Every time a batter connects with a ball, or the complex absorbs a photon of sunlight, the player on the field advances one base. When the fourth ball is hit, the player slides into home, scoring a run or, in the case of Photosystem II, releasing breathable oxygen. This research focused on the transition from S2 to S3, the last stable intermediate state before an oxygen molecule is produced.

The oxygen-evolving complex is surrounded by water and protein. In the step the scientists looked at, water flows through a pathway into the complex, where one water molecule ultimately forms a bridge between a manganese atom and a calcium atom. This water molecule likely provides one of the oxygen atoms in the oxygen molecule produced at the end of the cycle.

Using SLAC's Linac Coherent Light Source (LCLS) X-ray laser, the researchers found that water molecules are ferried into the complex as if through a bucket brigade: They move in many small steps from one end of the pathway to the other. They also showed that the calcium atom within the complex could be involved in shuttling the water in.

"It's like a Newton's Cradle," says Vittal Yachandra, one of the authors of the study and a senior scientist at Berkeley Lab who has been working on Photosystem II for more than 35 years. "Usually in liquid water things are constantly moving around, but now we are in this fascinating situation where some of the water molecules around the manganese cluster change their position, while others are actually always in the same place. You can repeat the experiment 10,000 times and they will still be sitting in that same spot."

Working in tandem

At LCLS, the team zapped samples from cyanobacteria with ultrafast pulses of X-rays to collect both X-ray crystallography and spectroscopy data to map how electrons flow in the oxygen-evolving complex of Photosystem II. Through this technique, they are able to simultaneously map its structure and uncover information about the chemical process at the manganese cluster.

Previously, the researchers had used this technique to make sure the sample was intact and importantly, also in the right intermediate chemical state. This paper marks the first time the researchers were able to merge the two sets of information to see connections between the structural and the chemical changes. This allowed the researchers to watch how the steps unfold in real time, and learn new things about the reaction.

"It is exciting to see the 'cause and effect' of changes induced by light absorption as they happen," Yachandra says.

"It is easy to forget how critical the environment is and how it enables these really complicated processes," says Junko Yano, one of the authors of the study and a senior scientist at Berkeley Lab. "Life does not happen in a vacuum; all components have to work together to make the reaction possible. These results show us how the protein and water molecules around the catalytic cluster work in tandem for making oxygen. Our results will start a new way of thinking and inspire new kinds of questions."

Ready, set, action!

Beyond photosynthesis, Yano says, this technique can be applied to other enzymatic systems to make more detailed snapshots of catalytic reactions.

"It allows us to connect the structural biology and chemistry of systems to understand and control complicated chemical reactions," she says.

The ultimate goal of the project is to piece together an atomic movie using many snapshots made throughout the process, including the elusive transient state at the end that bonds two oxygen atoms from two water molecules to form the oxygen molecule.

"Our dream is to go around the whole reaction cycle and get enough time points and details that you can see the entire process unfold, from the first photon of light coming in to the first molecule of breathable oxygen coming out," says co-author Jan Kern, a staff scientist at Berkeley Lab. "We've been building the set for this movie, establishing our technique and showing what's possible. Now the cameras are finally rolling and we can start working on the feature film."

Fluctuations in the Pacific Walker circulation (PWC), a zonally-oriented overturning cell across the tropical Pacific, can cause widespread climatic and biogeochemical perturbations. It remains unknown how the PWC developed during the Cenozoic era, with its substantial changes in greenhouse gases and continental positions. Yan and colleagues examined the evolution of the PWC across the Cenozoic using a suite of coupled model simulations on tectonic timescales. During the Early Eocene (ca. 54-48 Ma), when the Pacific was larger in size, the western edge of the PWC was ~18º west of its present position, in tandem with a 20º eastward expansion of the eastern edge. This leads to a significant broadening of the PWC by ~38º. As the climate cooled from the Early Eocene to the Late Miocene, the width of the PWC shrank, accompanied by an increase in intensity that was tied to the enhanced Pacific zonal temperature gradient. However, the locations of the western and eastern branches behave differently from the Early Eocene to the Late Miocene, with the western edge remained steady with time due to the relatively stable geography of the western tropical Pacific; the eastern edge migrates westward with time as the South American continent moves northwest. A transition occurs in the PWC between the Late Miocene and Late Pliocene, manifested by an eastward shift (both the western and eastern edges migrate eastward by >12º) and weakening (by ~22%), which they show here is linked with the closure of the tropical seaways.

Further sensitivity experiments that separate the influences of CO2 and land-sea configurations illustrate that rising CO2 alone leads to a weaker PWC, a robust feature across the large spread of Cenozoic climates considered here and therefore in a warmer future. The results also highlight that, at least on tectonic timescales, the location of the PWC is largely controlled by plate movements, with CO2 concentrations playing a secondary role impacting solely the intensity.

Although there are uncertainties to be considered, these results provide a testable relationship between the tectonic/CO2-induced climate change and the behavior of the PWC. The substantial changes in the PWC simulated here serve as a potential factor responsible for the reconstructed hydrological changes across the globe during the Cenozoic era. Moreover, a comprehensive understanding of the controls on the PWC could help advance its predictive skill and translate into better forecast of extreme weather conditions.

California isn't running out of water," says Richard Luthy. "It's running out of cheap water. But the state can't keep doing what it's been doing for the past 100 years."

Luthy knows. As a professor of civil and environmental engineering at Stanford, as well as director of a National Science Foundation center to re-invent urban water supply (known as ReNUWIt), he has spent decades studying the state's metropolitan areas.

In a new journal article, he argues that California cities can no longer rely on their three traditional water-coping strategies: over-drafting groundwater, depleting streams and importing water from far away. His analysis focuses on several strategies that, taken together, can help cities provide for their growing population with prudent public policies and investments:

CONSERVE

Conservation is cheap, says Luthy. Eliminating lawns or taking shorter showers are behavioral changes that don't require new spending on infrastructure.

Some cities have already made great strides. Los Angeles, for example, added 1.1 million residents between 1990 and 2010, but kept total water consumption flat through conservation, as homeowners and builders install things like low-flow toilets and high-efficiency washing machines. Similarly, two dozen San Francisco Bay Area cities cut total consumption by about 23% between 2004 and 2016 even as their populations grew by 10%.

But conservation isn't enough to match population growth. Although Southern California water officials recently predicted that by 2040 expanded conservation efforts should save enough water to supply about 2.3 million new residents, officials also expect population to grow by 3.1 million by then.

California can do more, Luthy says. About 10% of water distributed in urban areas is lost to leaks. Since the last drought, California utilities have conducted water loss audits to curb such waste. "Conservation is essential to help meet urban water demand, but we also need other measures to increase supply," Luthy says.

NON-POTABLE REUSE

The reuse of non-potable water for irrigation or other purposes has a long history in California. More than a century ago, cities like Fresno were reusing sewage water to irrigate surrounding farms. In the 1980s, the Irvine Ranch Water District built a dual-distribution system that now delivers 25 million gallons per day of purified non-potable water to farms and businesses.

Cities could do the same today, but to recycle non-potable water, planners would have to build pipe networks to separate the non-potable water from the drinking water, at a cost of between $1 million to $10 million per mile.

Most short-distance opportunities have already been implemented. That still leaves new opportunities for smaller, decentralized projects where wastewater is generated and needed. The Salesforce Tower in San Francisco, for example, will soon be recycling about 30,000 gallons of wastewater a day for all purposes except drinking. Distributed non-potable reuse is also catching on with tech campuses in Silicon Valley.

POTABLE REUSE

The real future, says Luthy, is potable reuse - making recycled water pure enough to drink.

Potable reuse is a process that begins by purifying wastewater in treatment plants and then feeding this cleansed water back into reservoirs or underground aquifers. Water utilities then mix the recycled water with new, fresh water to meet the standards for potability.

Orange County Water District has been a leader in potable reuse and the practice of "full advanced treatment" since 2004, and many other cities have plans to recycle at least some highly treated wastewater for drinking. For example, Los Angeles is currently considering an ambitious project to recycle virtually all its wastewater to eventually make it available for potable reuse by 2035 at a cost of $8 billion. A comparable project for the San Francisco Bay Area would involve expensive upfront infrastructure, but those initial outlays could ultimately be worth it as the supply of water imported from the Sierra decreases due to climate impacts and ecosystem needs, and the cost climbs, as expected, by 60% over the next decade.

CAPTURE

Billions of gallons of storm water simply pour into the ocean annually. That needs to change, Luthy says. California's coastal cities were historically engineered to flush out storm water to reduce flooding, but today cities want to capture as much as possible and put it to use. Los Angeles already gets 10% of its water from storm water runoff, and hopes to more than double that by 2035. Like potable reuse, however, storm water capture often requires big investments in pipes, storage sites and treatment facilities. The capital costs of such infrastructure vary widely, depending on local conditions. But the median project cost is often cheaper than costs to import water in the future, even assuming it will be available, Luthy says.

DESALINATE

The ocean has virtually limitless water, and some communities are taking advantage of desalination to meet their needs. San Diego Water Authority's desalination system, built at a cost of $1 billion, already delivers 50 million gallons per day - about 8% of its needs. But desalinating seawater is costly and energy intensive, and can harm marine life, which is why Luthy says other communities are desalinating brackish water from estuaries where rivers meet the sea. (Brackish water has a lower salt content than ocean water, which makes it easier and cheaper to treat.)

Alameda County already produces about 10 million gallons of drinking water per day by desalinating brackish groundwater in Newark. A partnership of five agencies in the Bay Area is considering a $200 million plant that could desalinate about 20 million gallons of brackish water per day from the North Bay estuaries for about the same cost per gallon as consumers currently pay to import water from the Hetch Hetchy Reservoir.

DEPOSIT

It's an ancient story that climate change makes increasingly common: too much rain and snow in wet years, and not enough in dry ones. One way to deal with these extremes is to "bank" extra water from wet years in underground aquifers. This is possible because the state's major metropolitan areas are linked by the 400-mile California Aqueduct. Cities in the north can "deposit" water in wet years by not taking withdrawals from the aqueduct and allowing that water to be pumped out and stored instead in Kern County, heart of the agricultural region near the end of the aqueduct. In dry years, northern cities could make "withdrawals" by taking extra water from the aqueduct and rely on the water stored in Kern County to be pumped back into the aqueduct, to make sure that enough water continues to flow to cities in Southern California.

"No single one of these measures will work in isolation, but if we plan wisely now, urban water will be available when we need it," Luthy says.

By studying the chemical elements on Mars today -- including carbon and oxygen -- scientists can work backwards to piece together the history of a planet that once had the conditions necessary to support life.

Weaving this story, element by element, from roughly 140 million miles (225 million kilometers) away is a painstaking process. But scientists aren't the type to be easily deterred. Orbiters and rovers at Mars have confirmed that the planet once had liquid water, thanks to clues that include dry riverbeds, ancient shorelines, and salty surface chemistry. Using NASA's Curiosity Rover, scientists have found evidence for long-lived lakes. They've also dug up organic compounds, or life's chemical building blocks. The combination of liquid water and organic compounds compels scientists to keep searching Mars for signs of past -- or present -- life.

Despite the tantalizing evidence found so far, scientists' understanding of Martian history is still unfolding, with several major questions open for debate. For one, was the ancient Martian atmosphere thick enough to keep the planet warm, and thus wet, for the amount of time necessary to sprout and nurture life? And the organic compounds: are they signs of life -- or of chemistry that happens when Martian rocks interact with water and sunlight?

In a recent Nature Astronomy report on a multi-year experiment conducted in the chemistry lab inside Curiosity's belly, called Sample Analysis at Mars (SAM), a team of scientists offers some insights to help answer these questions. The team found that certain minerals in rocks at Gale Crater may have formed in an ice-covered lake. These minerals may have formed during a cold stage sandwiched between warmer periods, or after Mars lost most of its atmosphere and began to turn permanently cold.

Gale is a crater the size of Connecticut and Rhode Island combined. It was selected as Curiosity's 2012 landing site because it had signs of past water, including clay minerals that might help trap and preserve ancient organic molecules. Indeed, while exploring the base of a mountain in the center of the crater, called Mount Sharp, Curiosity found a layer of sediments 1,000 feet (304 meters) thick that was deposited as mud in ancient lakes. To form that much sediment an incredible amount of water would have flowed down into those lakes for millions to tens of millions of warm and humid years, some scientists say. But some geological features in the crater also hint at a past that included cold, icy conditions.

"At some point, Mars' surface environment must have experienced a transition from being warm and humid to being cold and dry, as it is now, but exactly when and how that occurred is still a mystery," says Heather Franz, a NASA geochemist based at NASA's Goddard Space Flight Center in Greenbelt, Maryland.

Franz, who led the SAM study, notes that factors such as changes in Mars' obliquity and the amount of volcanic activity could have caused the Martian climate to alternate between warm and cold over time. This idea is supported by chemical and mineralogical changes in Martian rocks showing that some layers formed in colder environments and others formed in warmer ones.

In any case, says Franz, the array of data collected by Curiosity so far suggests that the team is seeing evidence for Martian climate change recorded in rocks.

Carbon and oxygen star in the Martian climate story

Franz's team found evidence for a cold ancient environment after the SAM lab extracted the gases carbon dioxide, or CO2, and oxygen from 13 dust and rock samples. Curiosity collected these samples over the course of five Earth years (Earth years vs. Mars years).

CO2 is a molecule of one carbon atom bonded with two oxygen atoms, with carbon serving as a key witness in the case of the mysterious Martian climate. In fact, this simple yet versatile element is as critical as water in the search for life elsewhere. On Earth, carbon flows continuously through the air, water, and surface in a well-understood cycle that hinges on life. For example, plants absorb carbon from the atmosphere in the form of CO2. In return, they produce oxygen, which humans and most other life forms use for respiration in a process that ends with the release of carbon back into the air, again via CO2, or into the Earth's crust as life forms die and are buried.

Scientists are finding there's also a carbon cycle on Mars and they're working to understand it. With little water or abundant surface life on the Red Planet for at least the past 3 billion years, the carbon cycle is much different than Earth's.

"Nevertheless, the carbon cycling is still happening and is still important because it's not only helping reveal information about Mars' ancient climate," says Paul Mahaffy, principal investigator on SAM and director of the Solar System Exploration Division at NASA Goddard. "It's also showing us that Mars is a dynamic planet that's circulating elements that are the buildings blocks of life as we know it."

The gases build a case for a chilly period

After Curiosity fed rock and dust samples into SAM, the lab heated each one to nearly 1,650 degrees Fahrenheit (900 degrees Celsius) to liberate the gases inside. By looking at the oven temperatures that released the CO2 and oxygen, scientists could tell what kind of minerals the gases were coming from. This type of information helps them understand how carbon is cycling on Mars.

Various studies have suggested that Mars' ancient atmosphere, containing mostly CO2, may have been thicker than Earth's is today. Most of it has been lost to space, but some may be stored in rocks at the planet's surface, particularly in the form of carbonates, which are minerals made of carbon and oxygen. On Earth, carbonates are produced when CO2 from the air is absorbed in the oceans and other bodies of water and then mineralized into rocks. Scientists think the same process happened on Mars and that it could help explain what happened to some of the Martian atmosphere.

Yet, missions to Mars haven't found enough carbonates in the surface to support a thick atmosphere.

Nonetheless, the few carbonates that SAM did detect revealed something interesting about the Martian climate through the isotopes of carbon and oxygen stored in them. Isotopes are versions of each element that have different masses. Because different chemical processes, from rock formation to biological activity, use these isotopes in different proportions, the ratios of heavy to light isotopes in a rock provide scientists with clues to how the rock formed.

In some of the carbonates SAM found, scientists noticed that the oxygen isotopes were lighter than those in the Martian atmosphere. This suggests that the carbonates did not form long ago simply from atmospheric CO2 absorbed into a lake. If they had, the oxygen isotopes in the rocks would have been slightly heavier than the ones in the air.

While it's possible that the carbonates formed very early in Mars' history, when the atmospheric composition was a bit different than it is today, Franz and her colleagues suggest that the carbonates more likely formed in a freezing lake. In this scenario, the ice could have sucked up heavy oxygen isotopes and left the lightest ones to form carbonates later. Other Curiosity scientists have also presented evidence suggesting that ice-covered lakes could have existed in Gale Crater.

So where is all the carbon?

The low abundance of carbonates on Mars is puzzling, scientists say. If there aren't many of these minerals at Gale Crater, perhaps the early atmosphere was thinner than predicted. Or maybe something else is storing the missing atmospheric carbon.

Based on their analysis, Franz and her colleagues suggest that some carbon could be sequestered in other minerals, such as oxalates, which store carbon and oxygen in a different structure than carbonates. Their hypothesis is based on the temperatures at which CO2 was released from some samples inside SAM -- too low for carbonates, but just right for oxalates -- and on the different carbon and oxygen isotope ratios than the scientists saw in the carbonates.

A model of a carbonate molecule next to an oxalate molecule

Oxalates are the most common type of organic mineral produced by plants on Earth. But oxalates also can be produced without biology. One way is through the interaction of atmospheric CO2 with surface minerals, water, and sunlight, in a process known as abiotic photosynthesis. This type of chemistry is hard to find on Earth because there's abundant life here, but Franz's team hopes to create abiotic photosynthesis in the lab to figure out if it actually could be responsible for the carbon chemistry they're seeing in Gale Crater.

On Earth, abiotic photosynthesis may have paved the way for photosynthesis among some of the first microscopic life forms, which is why finding it on other planets interests astrobiologists.

Even if it turns out that abiotic photosynthesis locked some carbon from the atmosphere into rocks at Gale Crater, Franz and her colleagues would like to study soil and dust from different parts of Mars to understand if their results from Gale Crater reflect a global picture. They may one day get a chance to do so. NASA's Perseverance Mars rover, due to launch to Mars between July and August 2020, plans to pack up samples in Jezero Crater for possible return to labs on Earth.

May 19th, 2020, Hong Kong - Insilico Medicine announces the publication of a new research paper titled "Molecular Generation for Desired Transcriptome Changes With Adversarial Autoencoders" in Frontiers in Pharmacology. This is the first study of this kind where novel molecular structures are created for a desired transcriptional response.

In this study, Insilico Medicine researchers developed a new model, the Bidirectional Adversarial Autoencoder, that learns a joint distribution of molecular structures and induced transcriptional response. The model can generate molecular structures for a given transcriptional response and vise versa. As a result, Insilico Medicine provided a model that combines both generative biology and generative chemistry. Using this model, researchers can run virtual screening, discover novel molecular structures, and predict transcriptional responses--one model to solve many problems.

"This paper shows that it is possible to generate novel molecular structures that induce the desired transcriptional response. At Insilico, we have been working on this project since 2016 and have created critical intellectual property covering the original ideas in generative biology proposed and patented by Alex Zhavoronkov and Alex Aliper. I hope that the generative chemistry and biology developed at Insilico will become household tools for big pharmaceutical companies. Many of these tools are available in our upcoming AI platform soon to be available for deployment at customer premises", said Daniil Polykovskiy, group leader at Insilico Medicine and senior author of the study.

In the next three decades we will need a 30-70 percent increase in food availability to meet the demand from an increasing population. And the global food system will need to change profoundly if it is going to provide humanity with healthy food that is grown sustainably in ways that are not only resilient in the face of climate change but also do not surpass planetary boundaries.

Research to date on the future of our food systems has largely focused on incremental changes possible with existing technologies. But even that research finds that incremental change will not be enough--we must radically transform our food systems.

Prompted by a conversation with the Bill and Melinda Gates Foundation, a new study in Nature Food led by the Commonwealth Scientific and Industrial Research Organisation (CSIRO) and the CGIAR Research Program on Climate Change, Agriculture and Food Security (CCAFS) offers insights into some disruptive, game-changing technologies that could make the difference for both people and the planet, and the social change needed to realize their potential.

"We have come to a point where business-as-usual is not an option," said Ana Maria Loboguerrero, a co-author of the study and the Climate Action research area director at the Alliance of Bioversity International and CIAT.

Investigating 75 emerging technologies, the study's authors identify an arsenal of highly promising options, many of them ready or near-ready. Their shortlist comprises technologies that not only contribute to a host of Sustainable Development Goals--climate action, reducing environmental impact, reducing poverty, healthy food--but can also be tailored to a range of institutional and political contexts. The diverse pipeline spans the entire food value chain, from production and processing to consumption and waste management.

Some we are already familiar with, such as artificial meats, 3D printing, drones, "intelligent" materials, and vertical agriculture. Others require a bigger stretch of the imagination: nitrogen-fixing cereals that don't need fertilizer, spreadable biodegradable polymers that conserve soil moisture, feed for livestock produced from human sewage. While the study focuses on the potential benefits of these technologies, it acknowledges there will be tradeoffs. And not only for the environment and human health--genetic modification of crops is already hotly debated; there is also the risk that unequal access to costly technologies across the globe could increase inequality. Transparency will be key to safeguarding against unintended negative social and environmental impacts, and appropriate policies and regulations are needed to ensure benefits are distributed fairly.

Building the social trust necessary for new technologies to take flight will be the foundation of transformative change, say the authors. "New technologies, especially the more controversial ones, require investment and political support to get off the ground. And for real implementation you need public support. Dialogue is the first step to repairing the trust between science and society--this paper aims to open a space for that dialogue," said Philip Thornton, CCAFS Flagship Program Leader and a co-author of the study.

"As many tech entrepreneurs see clearly, successful innovation requires a high failure rate. And with a challenge this big and this complex, we will need to attack from all sides. So while many of these technologies could yet fail, investment in their development and testing is crucial to the future of our food systems," said Mario Herrero, lead author and Chief Research Scientist at CSIRO. "Our research lays out what is needed to create the essential dialogue and the enabling environment that will accelerate the innovation we dearly need."

As people shelter in place to slow the spread of COVID-19, daily carbon dioxide (CO2) emissions have dropped by as much as 17 percent globally, according to a new study by the Global Carbon Project, an initiative led by Stanford University scientist Rob Jackson. Published in Nature Climate Change, the paper compiles government policies and activity data to pinpoint where energy demand has dropped off the most and to estimate the impact on annual emissions.

Jackson, a professor of Earth system science in Stanford's School of Earth, Energy & Environmental Sciences (Stanford Earth), sees in the study's findings the outlines of a greener economy and healthier society.

"People marvel at how quickly the air cleared when we stopped driving," Jackson said. "My son in Los Angeles called and said, 'Dad, the skies are blue!' The environment is resilient, and people are too."

Although the study's estimate of a 4 to 7 percent drop in global emissions this year may seem low, it will be the biggest emissions drop since World War II. The estimate reflects the fact that shelter-in-place rules are temporary and staggered across different countries, according to Jackson. Perhaps more surprisingly, U.S. emissions declined one third for part of April, a dramatic drop driven by reduced mobility, manufacturing and electricity demand.

History tells us the current emissions reductions may be short-lived. The recession of 2008 reduced CO2 emissions a percent and a half globally for one year, according to Jackson, who pointed out that emissions "roared back" five percent the next year because nothing had changed in terms of fossil-fuel infrastructure. By contrast, the oil shocks of the 1970s were specific to our fossil-fuel use and, therefore, more transformative. They led to everything from smaller cars to the birth of the solar and Alaskan oil industries.

Almost $50 billion of stimulus funding after the 2008 recession helped transform wind and solar power and energy conservation. "We're still reaping the benefits today from green power, historically cheap wind and solar contracts and a clean-energy industry that employs three million Americans," Jackson said. "We have the same chance to reshape transportation now. We could start by freeing up the $40 billion in low-interest loans currently idled in the Department of Energy's clean energy and advanced vehicle loan programs."

"Opportunities exist to make real, durable, changes and be more resilient to future crises, by implementing economic stimulus packages that also help meet climate targets, especially for mobility, which accounts for half the decrease in emissions during confinement,” said study coauthor Corinne Le Quéré, a professor of climate change science and policy at the University of East Anglia. “For example in cities and suburbs, supporting walking and cycling, and the uptake of electric bikes, is far cheaper and better for wellbeing and air quality than building roads, and it preserves social distancing."

The pandemic could change commuting and transportation permanently, according to Jackson. "Cities from Milan to Seattle are closing miles of streets to traffic permanently and opening them to pedestrians and bicyclists. Telecommuting, even part time, might be the new normal. Traffic congestion has vaporized. Electric cars are fast and can be fossil-free, changing a sector of the economy that's been hard to decarbonize."

Jackson also expressed hope that a post-pandemic recovery strategy would focus on solutions for underprivileged communities more vulnerable to both climate change impacts and diseases such as COVID-19. "People of color and the poor live closer to coal-fired power plants and car-heavy freeways - the two biggest sources of air pollution that kill hundreds of thousands of Americans a year," Jackson said. "Clean power coupled with electric cars could give everyone clean air without sheltering at home."

Scientists from Hong Kong Baptist University (HKBU) have developed a novel technique that can produce pure therapeutic drugs without the associated side effects.

The approach, which uses a nanostructure fabrication device, can manipulate the chirality of drug molecules by controlling the direction a substrate is rotated within the device, thus eliminating the possible side effects that can arise when people take drugs containing molecules with the incorrect chirality.

Published in the renowned international scientific journal Nature Chemistry, the research findings pave the way towards the mass production of purer, cheaper and safer drugs that can be made in a scalable and more environmentally-friendly way.

Control of molecular chirality improves drug safety

Many chemical molecules have two configurations, or chiral versions, that are mirror images of each other. While sharing the same molecular formula, the two chiral versions have different arrangements of their constituent atoms in space. The two versions of the molecules are characterised by left-handed and right-handed chiral configurations like human hands. Molecules with "left-handed" and "right-handed" chirality can have totally different biochemical effects.

More than half of the therapeutic drugs are made up of equal amounts of left-handed and right-handed chiral molecules, commonly known as "racemates"; one can cure specific diseases, but the other may have adverse effects. Separating and producing molecules with only the chiral arrangement (known as a single enantiomer) responsible for the therapeutic effects can help to produce drugs with improved safety and efficacy.

Macro-scale control of molecular chirality

In general, molecules have an extremely small size ranging from one-millionth to one hundred-thousandth of the diameter of a human hair. It is therefore extremely challenging to selectively produce one of the two chiral molecule versions using "macro-scale" control (i.e. the dimensional scale that can be seen using the naked eye and operated by hand). To produce single-enantiomer drugs, chemists have overwhelmingly used molecules called "chiral ligands" to effectively control the molecular chirality of drugs in the laboratory or industry at the molecular scale, a process called asymmetric synthesis. However, the existing technologies for producing single-enantiomer drugs are composed of complicated procedures, which are expensive and environmentally-unfriendly.

Dr Jeffery Huang Zhifeng, Associate Professor in the Department of Physics at HKBU, and his research team devised a novel approach to manipulating molecular chirality through macro-scale control in collaboration with Sichuan University, Guangxi Medical University and the Southern University of Science and Technology. It involves mediating the manipulation with helical metal nanostructures (i.e. metal nanohelices) that are in the shape of a helical spring, and they have a characteristic size of one-thousandth of the diameter of a human hair.

Direction of rotation determines molecular chirality

The research team fabricated the metal nanohelices using a nanofabrication technique called glancing angle deposition (GLAD). Silver and copper were deposited onto a supporting substrate that was rotated clockwise and counterclockwise to fabricate the right-handed and left-handed metal nanohelices, respectively.

The research team then used ultraviolet light to induce a chemical reaction. This caused 2-anthracenecarboxylic acid (AC) molecules adsorbing on the metal nanohelices to undergo the chemical reaction and form chiral molecular products, which are similar to some chiral drugs. When AC was attached to the surface of the right-handed metal nanohelices and exposed to ultraviolet light, it preferentially produced "right-handed" chiral molecular products. By the same token, when AC was adsorbed on the surface of the left-handed metal nanohelices and exposed to ultraviolet light, it preferentially produced "left-handed" chiral molecular products. In other words, the chirality of the molecular product can be reliably determined by the chirality of the metal nanohelices, which is controlled by the direction of substrate rotation.

The research demonstrates that controlling the direction of substrate rotation at a macroscopic level can conveniently manipulate molecular chirality. This is an unprecedented application of the macro-scale method (through the control of the rotation direction of a 4-inch substrate holder) to manipulate chirality at the molecular-scale (chiral molecular products in the range of one-billionth of a metre).

Green approach to reducing drug side effects

"Our success in manipulating molecular chirality through macroscopic engineering allows the convenient synthesis of drugs in single-enantiomer forms with only left- or right-handedness. Hence, it will help get rid of the adverse, sometimes fatal, side effects of many therapeutic drugs," said Dr Huang.

The use of chiral ligands in the conventional method of asymmetric synthesis is inevitable, and it may cause pollution to enter the environment. In contrast, in this novel approach the metal nanohelices can be used repeatedly to produce single-enantiomer drugs without the use of chiral ligands. As a result, it paves the way towards the mass production of affordable therapeutic drugs that are made in a scalable manner with recyclable materials.

Chemical compounds found in many consumer products could be major contributors to the onset of lipid-related diseases, such as obesity, in humans, according to a Baylor University study.

Until recently, scientists thought that diseases such as obesity and fatty liver resulted from anomalies in the metabolism of lipids triggered by excessive energy intake, fat consumption and lack of physical activity. But the Baylor study, published in the international journal Toxicology and Applied Pharmacology, highlights the existence of chemical compounds people are exposed to via a variety of consumer products. These can lead to lipid-related metabolic diseases and weight gain.

"Previous studies have provided strong evidence linking some hormone-like compounds to obesity in humans, but this is the first study that showed a cellular and metabolic effect on human cells exposed directly to those compounds," said Ramon Lavado, Ph.D., assistant professor of environmental science at Baylor.

Lavado's team has been conducting experiments to determine whether their suspicion that obesogens -- specific chemical compounds found to disrupt normal metabolic processes -- promoted a dysregulation of lipid profiles in the human liver.

While poor nutrition and lack of exercise are known contributors to obesity, significant attention has emerged regarding the potential effects of some chemical compounds to trigger lipid-related diseases, Lavado said. Exposures to obesogens -- particularly in early development in life -- were found to disrupt normal metabolic processes and increase susceptibility to weight gain across the lifespan, he said.

As of the year 2000, there were an estimated 100,000 commercially available chemicals around the world. Two decades later, that amount has more than tripled, with approximately 350,000 chemicals being available, according to recent research published in Environmental Science & Technology.

Contributing chemicals to the diseases may be found in cigarette smoke, air pollution, pesticides, fungicides, flame retardants and a certain class of chemicals used in many consumer products to make them softer. Other contributors widely used in the past may have been industrial chemicals in paints, cements, fluorescent light ballast, sealants and adhesives.

For the study, Lavado said that he and his team used well-established techniques in the field of metabolomics and molecular toxicology to investigate whether the proportion of lipids related to diseases, such as obesity, was modified upon exposure to environmental obesogens -- and if so, to what extent the lipid profile changed. Additionally, they used a technique called fluorescence microscopy to investigate whether environmentally relevant concentrations of the tested compounds had the ability to induce fat accumulation in liver tissue.

Study results indicated that the production of diglycerides and triglycerides increased significantly, while other less harmful lipids were found in smaller proportions, said Marco Franco, a Baylor doctoral candidate in environmental science in Lavado's research group. Another novel finding was that those effects were observed in cells exposed to chemical concentrations that are often seen in the environment and to which people are exposed constantly.

This study is among the few that report molecular and physical changes at the cellular level, and the quantification of specific types of lipids that emerge as a result of chemical exposure, Lavado said.

"In the case of lipid profile alterations, the idea that chemical compounds may trigger and/or contribute to the development of lipid-related diseases deserves extensive research in the future," he said.

Additionally, study results strongly support the use of animal alternatives with more human relevance as a valuable tool in the characterization of health effects caused by chemicals for which humans are often exposed but lack thorough toxicological data, Lavado said.

Barcelona, 19 May 2020.- Knowledge of how a molecule interacts with the organism is crucial in order to consider its therapeutic potential. Headed by ICREA researcher Patrick Aloy, the Structural Bioinformatics and Network Biology (SBNS) lab at IRB Barcelona has presented the Chemical Checker, an on-line open-access tool that provides information on the effects exerted by more than 1M compounds in a wide range of biological settings. The Chemical Checker, published in Nature Biotechnology, offers a rich portrait of the small molecule data available in the public domain, opening an opportunity for making queries that would otherwise be impossible using chemical information alone.

The SBNB lab has already proven the tool's potential by reverting Alzheimer's disease's gene alterations in vitro, using approved drugs and experimental compounds. These scientists have also identified several compounds that could potentially substitute 'biologics' as treatments, such as antibody therapies, which show high specificity and efficiency, but are expensive and prone to pharmacokinetic issues. "We envision many applications for the Chemical Checker in the drug discovery process," explains Aloy "such as the formulation of logical queries to prioritize drug repositioning and combination opportunities, based on desired bioactivity traits."

The similarity principle

The Chemical Checker works upon the similarity principle. Similar compounds not only show analogous chemical properties but also share biological behaviour. Molecules with similar cell-sensitivity profiles or eliciting similar side-effects often have the same mechanism of action, even when their chemical structures appear to be unrelated.

The so-called 'similarity principle' has been the driving force of drug discovery and, in one flavour or another, the calculation of compound similarities lies behind most of the methods used to chart and exploit the chemical space. Evidence suggests that 'biological' similarities offer an alternative means to navigate chemical space, possibly unveiling non-obvious, clinically relevant similarities between compounds.

Five levels of increasing complexity

A drug is often an organic molecule (Chemistry) that interacts with one or several protein receptors (Targets), triggering perturbations of biological pathways (Networks) and eliciting phenotypic outcomes that can be measured in cell-based assays (Cells) before delivery to patients (Clinics). The Chemical Checker tool offers information of small molecules in these five levels of increasing complexity: Chemistry, Targets, Networks, Cells and Clinics.

"With the Chemical Checker, we are pushing the similarity principle beyond chemical properties, reaching various ambits of biology and enabling the right level of experimental detail at each step of the drug discovery pipeline," explains Miquel Duran.

A collaboration with Amazon to target COVID

The Chemical Checker has already led to a collaboration with Amazon to make available an open access database to provide researchers from around the world with an expanded portfolio of molecules with the potential to fight COVID-19. Amazon's expertise in text-mining, machine learning and natural language understanding has allowed the automatic analysis of scientific articles to be incorporated into the Chemical Checker.

To facilitate data access, the SBNB lab has built a web-based resource which allows users to run similarity searches for a given compound across the 25 available Chemical Checker bioactivity spaces. The full code of the resource and Chemical Checker signatures can be downloaded from the web, or simply accessed via a programming interface. The COVID platform is available here.

Scientists engineering valuable microbes for renewable fuels and bioproducts have developed a fast, efficient way to identify the most promising varieties.

Researchers at the University of Illinois at Urbana-Champaign developed a novel mass spectrometry-based screening technique to rapidly profile medium-chain fatty acids produced in yeast -- part of a larger group of free fatty acids that are key components in essential nutrients, soaps, industrial chemicals, and fuels. They also identified seven new genetically engineered mutants of the yeast Saccharomyces cerevisiae that produce higher levels of those fatty acids.

The study is detailed in a paper published in the journal Biotechnology and Bioengineering. The research was performed at the Center for Advanced Bioenergy and Bioproducts Innovation (CABBI), a U.S. Department of Energy-funded Bioenergy Research Center, by two U of I professors: Huimin Zhao, Professor of Chemical and Biomolecular Engineering (ChBE), and Jonathan Sweedler, Professor of Chemistry and Director of the School of Chemical Sciences. The lead author is Pu Xue, a ChBE doctoral student with Zhao's lab at CABBI.

Zhao's group genetically engineers tiny yeast cells to increase production of fatty acids, crucial components of biodiesel, fatty alcohols, waxes and olefins -- the building blocks for detergents, adhesives, and plastics. CABBI's goal is to develop robust yeasts that can convert renewable plant biomass to fuels and chemicals, as an environmentally friendly and sustainable alternative to petroleum-based chemical manufacturing processes.

Scientists can create a large library of engineered yeast strains, or mutants, producing various MCFAs very quickly, Xue said. But their ability to control the exact composition of MCFAs produced in these microbial cell factories is limited, with no "high-throughput" way to quickly analyze large numbers of samples.

To overcome this limitation, Xue and other researchers worked with Sweedler's group to develop a high-throughput screening tool, a chemical characterization approach based on MALDI-ToF MS (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry). Mass spectrometry is an information-rich way to analyze complex samples by measuring their mass-to-charge ratio of ions. A laser is shot at a colony of yeast on a slide; the instrument measures the molecular masses of the lipids in the yeast, and thus is able to identify them.

Most existing processes for detecting or analyzing free fatty acids rely on more complex gas or liquid chromatography-mass spectrometry, considered the gold standard methods. But those methods have limitations when dealing with a large pool of variations, and preparing samples is time-consuming and labor-intensive.

The overall approach using the MALDI-ToF MS system is faster and has been used successfully with proteins and peptides. The ToF mass analyzer is fast, relatively low cost and has a large detection window, well-suited for screening complex biological targets.

But medium-chain fatty acids are highly volatile and lightweight, making them harder to detect and quantify with this approach. Moreover, the thick cell wall of yeast creates another challenge for researchers to decompose cellular compositions efficiently.

So the CABBI researchers optimized the sample preparation steps with various solvents and matrices. And instead of trying to directly detect the MCFAs, they used a proxy: membrane lipids in yeast cells. They hypothesized that increased levels of membrane lipids with shorter acyl chain phosphatidylcholines (PCs), a class of phospholipids, would correlate with a greater capacity to produce MCFAs, which are shorter in length than the abundant fatty acids commonly found in S. cerevisiae.

To validate that hypothesis, U of I scientists compared the MALDI-ToF MS profile of the naturally occurring yeast with two genetically engineered strains previously found to produce higher levels of MCFAs. The data showed that these two mutants had more of the shorter acyl chain PCs than the naturally occurring yeast. Those preliminary findings were then confirmed by the more exact liquid chromatography and fragment mass spectrometry processes.

With their established screening method in hand, CABBI team members set out to find more mutant strains with higher production of MCFAs. They found two prominent peaks on the mass spectrum that were correlated with the phospholipids, an indication of fatty acids. Those were then used as a sign of MCFA production.

As Sweedler points out, "the mass spectrometry measurement is fast -- analyzing up to 2,000 yeast colonies per hour (approximately one sample every two seconds) compared to 30 minutes per sample under traditional methods." The processing time is also significantly shortened: two to three minutes vs. three to four hours per sample. Overall, the MALDI-ToF MS screening tool allows scientists to quickly identify strains that warrant more detailed analysis.

"Our method allows us to screen tons of mutants in a short time. We can identify the good candidates for further study," Xue said.

In the future, the method can be modified and used for high-throughput screening of other types of products, such as longer-chain fatty acids or fatty alcohols, saving time and labor.

The researchers hope to build on their work at CABBI's iBioFAB -- the Illinois Biological Foundry for Advanced Biomanufacturing. Its robotic system can speed up sample preparation and provide faster, more accurate results, helping scale up the project to test many more mutant strains, Xue said. With about 6,000 genes in S. cerevisiae, millions of potential synergistic effects and features could be discovered.

Beyond science, these C6 to C12 fatty acids are important in human health, providing critical nutrients and useful products, such as Omega-3 fatty acids.

"In the future if we can directly generate biofuels and bioproducts such as fatty acids from microbial cells like yeast in large scale, that means we don't need to use petrol," Xue said. "We can save the environment and save a lot of money as well."

Millions of acres of natural habitat in the U.S. and the wildlife that inhabit these large swaths of private and public lands depend on people who support a myriad of conservation activities. Recreational hunters are an important group of people whose licenses, taxes and fees directly pay for conservation efforts. However, the number of people who hunt as a sport has steadily declined since the 1980s.

"In some states, more than half of funding for state conservation agencies comes from hunters and fishermen. When they leave the sport, there are less funds to do everything from restoration projects to prescribed burns," said Kevin Ringelman, who is a waterfowl ecology and management assistant professor in the LSU School of Renewable and Natural Resources.

He and his colleagues, Associate Professor Bret Collier and instructor Luke Laborde, train LSU wildlife ecology students, who become the professionals responsible for managing the biodiversity of natural systems for species conservation. These wildlife professionals conduct science and collect data that inform the policies to protect natural resources, and implement the management practices. They also interact with stakeholders many of whom are hunters. As part of their students' training for wildlife management careers at LSU, Ringelman and Collier have developed a unique, professional development experience: hunting.

"The hunting experience is transformative for our students, resulting in a deeper connection to the wildlife resource, and a richer understanding of the hunting culture and hunters' stewardship for wildlife habitat," they write in a new paper published this week in The Journal of Wildlife Management.

Along with colleagues at the University of California Davis, they describe how the consumptive interaction with nature--the act of harvesting an animal--leads to a deeper appreciation of the resource.

"I tell them it is an oath. We take from the marsh with gratitude and so we must give back with generosity," said co-author John Eadie, the Dennis G. Raveling Professor at UC Davis, who works with the California Waterfowl Association to administer a similar program.

Hunting as a sport in the U.S. became popular after World War II with the baby boomers, who had time, disposable income and an appreciation for nature. It also coincided with the advent of wildlife and natural resource management programs in the U.S. Hunting peaked in the 1970s when about 7 percent of the U.S. population participated in hunting as a recreational pastime.
Since then, the sport has experienced a steady decline as hunters have begun to age out and subsequent generations have been less interested in the sport.

"There are several reasons why people are not taking up hunting as a sport now - namely, the lack of time, lack of access to the outdoors as rural communities become urban and suburban, choosing 'screen time' over going out into nature and the overall loss of a hunting culture," Ringelman said.

According to the latest U.S. Fish and Wildlife Service survey, there are more than 2.2 million fewer hunters in the U.S. today.

"Right now, less than 4 percent of the U.S. population is a hunter. As a result, our current students are less likely to be hunters than previous generations of wildlife management students," Collier said.

He finds this trend concerning because future wildlife professionals are better equipped to manage wildlife resources and develop policies if they understand the motivations and culture of the hunter constituents that support their work.

To address this problem, Collier and Ringelman have developed one of the few sustaining university hunting programs in the U.S. In collaboration with private duck hunting clubs that provide lodging and professional guides as well as non-governmental organizations and industry that donate the materials for the program, they consistently offer this voluntary opportunity to all senior wildlife management undergraduate majors at LSU, which is about 34 students per year.

The students learn about gun safety and get to practice on a clay target range at a professional hunting lodge. Before dawn, a professional guide leads each small group on a hunt in the marsh. To see this unique educational experience, watch this video.

After each hunting field trip, the students return to LSU to conduct scientific dissections of the game they harvested to learn about the anatomy and foraging ecology of the species.

"The point of this program is not harvest. We are creating the next generation of stewards of conservation. If we're teaching students holistically about wildlife, then you can't just end a program with harvest," Collier said.

From his experience introducing hunting to his students at LSU, he sees college students as an untapped group of people who could be part of a resurgence in the sport.

"College students are self-sufficient, independent, have transportation and disposable income as well as a group of peers who share interests," Collier said.

Ringelman also sees hunters' values of getting back to nature, being self-sufficient and sourcing ethical protein as ideals that resonate with millennials and Generation Z.

"It's another avenue for recruiting new hunters," Ringelman said.

Researchers from Prokhorov General Physics Institute of the Russian Academy of Sciences and the Moscow Institute of Physics and Technology have developed a novel method for diagnosing and monitoring autoimmune disorders. Within a mere 25 minutes, their new biosensor not only measures the concentration of autoantibodies in human blood serum with extremely high sensitivity, but also -- for the first time -- quantifies their activity. The combination of these parameters permits the elaboration of new diagnostic criteria for autoimmune diseases, as well as new approaches to their treatment. The paper was published in Biosensors and Bioelectronics, the highest-ranking scientific journal in the field of biosensing technology and analytical chemistry.

Autoantibodies produced by the immune system misinterpret the organism's cells and organs as targets, causing autoimmune disorders. The autoantibodies are associated with more than 80 serious autoimmune diseases ranging from rheumatoid arthritis, psoriasis, and lupus to multiple sclerosis and Type 1 diabetes. Many of them require lifelong care and treatment to alleviate suffering. Autoantibodies are present in the blood of about 10% of the population. Due to a high prevalence of autoimmune disorders, the economic impact is enormous and is estimated for some countries as twice that of cancer. Autoantibodies appear in blood long before clinical onset, and their characteristics can be used to foresee disease activity and severity.

Currently, the treatment of autoimmune diseases is substantially complicated due to dramatic variations in the results of commercial tests by different manufacturers.

"Depending on the laboratory running the test, and the method used, the autoantibody concentration measured in the same sample at the same time may vary by a factor of 10," says one of the paper's authors Alexey Orlov, a senior scientist of the Biophotonics Lab at GPI RAS and Nanobiotechnology Lab at MIPT, a 2010 graduate of MIPT. "In fact, no one could rely on autoantibody concentration as a quantitative parameter to evaluate therapy efficiency."

Such inconsistencies in test results stem from the complex nature of autoantibodies. An autoantibody comprises a set of many heterogeneous molecules that interact with each other and with a target in substantially different ways. Until now, no technique has provided the capacity to account for this factor.

Also, the existing methods, widely used in the clinical practice, do not provide the option to characterize antibody activity -- the parameter that shows how destructive the antibodies are to target tissues. The authors have developed a tool that addresses both issues at once: It performs rapid high-sensitivity measurements of autoantibody activity and concentration.

Another innovative feature is the simultaneous determination in a single sample of the concentration and activity of autoantibodies to several targets. Such approach substantially increases the diagnostic merit of the solution because different levels of autoantibodies to dissimilar targets may be indicative of distinct diseases. A correlation analysis of the data concurrently obtained on multiple autoantibodies can considerably enhance the accuracy of diagnostics.

"That is why we call our system multiplex, or multiparametric," mentions study co-author Averyan Pushkarev, an MIPT doctoral student and 2018 alumnus. "One strong advantage is the consumables used in our technique: We use a standard microscope cover glass. Its low cost is especially important for mass medical diagnostics, which requires disposable consumables."

While the study demonstrates the simultaneous characterization of antibodies to two targets, the team is working on increasing that number. Using the microchip technology, for example, thousands of 100-micron-sized targets can be deposited on a glass slip.

In the new technique, a drop of patient blood serum is passed over the glass slip surface. If antibodies are present in the serum, they find their targets deposited on the glass and bind to them, increasing the biolayer thickness on the glass. Under the glass slip, there is an interferometry system developed at GPI RAS. This unique optical reader enables real-time measurements of the thickness of the molecular layer in each spot on the glass surface.

"A fundamentally important detail: Unlike a multitude of other methods, we have the autoantibodies interact with moving targets rather than those immobilized on a surface," Orlov adds. "This is the first-ever solution that allows the investigation of autoantibody interaction with targets in their natural form and environment, as they are present in a living organism."

This is achieved as follows (fig. 1). Once an autoantibody binds to a target on the glass, the researchers pump a solution of free target molecules along the glass. At that point, the authors implement an approach that no one has been able to put into practice for the mentioned important task. Each autoantibody possesses one or more recognition fragments, known as Fab-fragments or "hands," which can recognize and grab targets. In the test, an autoantibody grabs the immobilized target with one "hand" and uses the others to catch mobile targets from the serum sample. This process delivers quantitative data on the actual (native) activity of antibodies. Moreover, this setup, on the one hand, provides autoantibody immobilization on the glass in their natural form, and on the other hand, minimizes the binding of foreign components that may affect the results.

"We have developed not only an efficient diagnostic test but also a unique tool for the investigation of autoantibodies," comments the paper's senior author Petr Nikitin, who heads the Biophotonics Lab at GPI RAS and is a 1979 graduate of MIPT. "Using patient blood samples, we have demonstrated that the quantitative parameter of autoantibody activity is independent of their concentration. The clinicians now have a tool for quantitatively monitoring both key parameters in the course of a disease, and elaborating novel advanced methods for the diagnostics and treatment of autoimmune disorders."

What drives the evolution of new species of sharks and rays? Traditionally, scientists thought it required species to be separated by geographic or spatial barriers, however a new study of elasmobranchs (the group of sharks and rays) has challenged this expectation - and found evolution is happening faster than many think.

Flinders University evolutionary biologists Dr Jonathan Sandoval-Castillo and Professor Luciano Beheregaray tested how different oceanographic conditions in the Gulf of California and the Baja California Peninsula (Mexico) influenced the formation of new species of guitarfish (genus Pseudobatos).

The team discovered four types, or 'young species', of guitarfish that have similar external appearance but are genetically different.

Each type of guitarfish appears to have adapted to one of the four separate regions of the Gulf of California. This promotes environmental tolerances which result in those guitarfish having improved odds for survival and reproduction in the region where they were born.

"We have shown that these four guitarfish species evolved quite quickly from the same common ancestor," says Dr Jonathan Sandoval-Castillo.

"The process where several new species originate from one ancestor in a relatively short period of time is called adaptive radiation, and this is the first report of such a process in sharks and rays. Our results help changing the false popular belief that sharks and rays do not evolve, or only evolve very slowly," says Prof Luciano Beheregaray.

These findings also have important implications for the management of exploited elasmobranch species, such as guitarfish in the Gulf of California which represents an important fishery for Mexico.

If these young species adapt and evolve to their local habitat conditions, they cannot be replaced by migrants from other habitats.

"If such species are incorrectly managed as a single stock, it can result in the over-exploitation and possibly extinction of the entire species."

Barcelona, 18 May 2020.- The Translational Control of Cell Cycle and Differentiation Lab at IRB Barcelona, led by ICREA researcher Raúl Méndez, has published a study in the journal Science Advances that has identified a key factor in the development of luminal breast cancer. Characterised by the expression of estrogen receptors, luminal tumours are the most common subtype of breast cancer. The mammary gland is the only organ in our body to undergo its greatest development after birth, as a result of fluctuations in hormone levels. This makes this gland a good model to study cell differentiation and also the mechanisms that regulate the progression of breast cancer.

"Traditionally, much attention has been devoted to the in-depth study of how hormones regulate the development of the mammary gland at the transcriptional level, that is, the synthesis of messenger RNA from DNA. In previous work by our group, we had discovered that factors called CPEBs regulate the next step, namely the translation of that messenger RNA into protein. This process is crucial for embryo development, and it is deregulated during the development in tumours other than those in the breast, such as those of the pancreas," explains Méndez.

The IRB Barcelona research team has discovered that CPEB2 is essential for protein synthesis after hormonal stimulation, the latter a process that regulates both the proper development of the mammary gland and the formation of luminal breast tumours.

To this end, the study generated new mouse models in which each of the four members of the CPEB family was inactivated. These models allowed the researchers to reveal CPEB2 as a key piece in the estrogen signalling pathway. Without this factor, the most important mediators activated through the estrogen receptor are not synthesised and, therefore, the response to hormone receptors decreases.

"The study allows us to affirm that cells proliferate less in the absence of CPEB2. We have seen in vivo that mice genetically engineered not to express CPEB2 are protected against luminal breast cancer," explains Rosa Pascual, first author of the article.

Likewise, the research reveals, using human data, that luminal breast cancer patients with low expression of CPEB2 have a better prognosis.

In this regard, if the effects detected in mice were replicated in human trials and the side effects were minimal, CPEB2 could provide a new therapeutic target.

Thus, a CPEB2 inhibitor could be a good candidate in combination with current therapies that block the estrogen signalling pathway, or as an alternative for those patients with luminal tumours that are resistant to hormone receptor-based treatments at the transcriptional level.