Earth

Photosynthesis varies greatly across rice cultivars--natural diversity could boost yields

image: University of Illinois Graduate Student Liana Acevedo-Siaca examined 14 diverse rice varieties to discover natural differences in how the plants harness light energy to fix carbon dioxide into food. In a recent study, she found a 117 percent difference in fluctuating light conditions, suggesting a new trait for breeder selection.

Image: 
International Rice Research Institute

Rice is a direct source of calories for more people than any other crop and serves as the main staple for 560 million chronically hungry people in Asia. With over 120,000 varieties of cultivated rice (Oryza sativa) across the globe, there is a wealth of natural diversity to be mined by plant scientists to increase yields. A team from the University of Illinois and the International Rice Research Institute (IRRI) examined how 14 diverse varieties photosynthesize--the process by which all crops convert sunlight energy into sugars that ultimately become our food. Looking at a little-studied attribute of photosynthesis, they found small differences in photosynthetic efficiency under constant conditions, but a 117 percent difference in fluctuating light, suggesting a new trait for breeder selection.

"Photosynthesis has traditionally been assessed under 'constant conditions' where plants are exposed to constant, high levels of light, but field conditions are never constant, especially considering the light that drives photosynthesis," said RIPE Director Stephen Long, Ikenberry Endowed University Chair of Plant Biology and Crop Sciences at Illinois' Carl R. Woese Institute for Genomic Biology. "We looked at 14 cultivars of rice that represent much of the crop's diversity and asked the question: could there be variability in photosynthesis in fluctuating light that we might be able to capitalize on?"

Published in New Phytologist, this work is part of Realizing Increased Photosynthetic Efficiency (RIPE), an international research project that enables crops to turn the sun's energy into food more efficiently to increase global production sustainably with support from the Bill & Melinda Gates Foundation, the U.S. Foundation for Food and Agriculture Research (FFAR), and the U.K. Government's Department for International Development (DFID).

"If you look within the canopy of leaves of any crop, you will see that the light is fluctuating by one or two orders of magnitude," Long said. "A plant's access to light is not only impacted by clouds intermittently obscuring the sun but much more commonly by its own leaves, or those of a neighboring plant, as the sun's angle changes throughout the day. Calculations show that the photosynthetic inefficiency imposed by these leaves slowly adjusting to each fluctuation in light may cost crops 20 to 40 percent of their potential productivity."

The researchers compared results from constant and fluctuating light conditions and found no correlation, which supports findings from a 2019 study on cassava. In other words, varieties that do well in fluctuating light might not do well in constant light and vice-versa, suggesting that selection for these traits should be conducted independently.

"This lack of correlation, which seems to be consistent across species, calls for us to flip how we think about studying photosynthesis," said first-author Liana Acevedo-Siaca, a graduate student in the College of Agriculture, Consumer, and Environmental Sciences (ACES). "Moving forward, we need to incorporate more dynamic measurements into the way that we understand photosynthesis, especially in an agricultural setting, because realistically those plants are never in a steady-state."

The team also evaluated how these plants cope with fluctuations in light intensity across the five major rice groups, sometimes considered to be subspecies. While no group appeared better than the other overall, the team believes that variation could be found in future research.

In this study, three photosynthetic parameters were of particular interest: the speed of induction (how quickly photosynthesis activates, or starts), speed of assimilation (how quickly the plant physically fixes carbon into sugar), and how efficiently these rice plants use water.

After switching from low light to high light, one variety activated (or began photosynthesizing) 117 percent faster than the slowest. In fluctuating light conditions, another variety from the Indica group assimilated more than double that of the "worst" variety (also an Indica), which was found to be the most water-use efficient variety.

"Surprisingly, after making a more detailed analysis of these accessions, along with a well-studied control called IR64 from the Philippines, we found that biochemistry is the biggest limitation to efficiency as leaves transition from shade to sun," Long said. "Biochemistry is a different limitation altogether than that found in a parallel study of cassava, illustrating the need to fine-tune photosynthesis separately in different crop species--despite the fact that the photosynthetic process is generally well-conserved and consistent across most food crops."

According to Acevedo-Siaca, the next step is to identify how to breed for (or engineer) rice with faster induction responses.

"At the end of the day, the goal would be to have plants that can respond more quickly to light fluctuations to enable them to be more productive," said Acevedo-Siaca, a 2016 recipient of the U.S. Borlaug Fellowship in Global Food Security that supported her to conduct much of this research at IRRI. "I am interested in ways that we can improve this process while preserving some of the germplasm we have out there. There's so much diversity with which we could work. I think it would be a shame if we didn't examine all of our options more deeply."

Long also published a landmark study in Science that showed crops are not fully adapted to deal with the dynamic light conditions in fields--and helping them can increase crop productivity by as much as 20 percent. The RIPE project and its sponsors are committed to ensuring Global Access and making the project's technologies available to the farmers who need them the most.

Credit: 
Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign

'Primitive' stem cells shown to regenerate blood vessels in the eye

image: Human vascular progenitor cells (green), made from Zambidis' lab-grown naive stem cells, engraft into blood vessels (red) in a mouse retina.

Image: 
Elias Zambidis, Johns Hopkins Medicine

Johns Hopkins Medicine scientists say they have successfully turned back the biological hands of time, coaxing adult human cells in the laboratory to revert to a primitive state, and unlocking their potential to replace and repair damage to blood vessels in the retina caused by diabetes. The findings from this experimental study, they say, advance regenerative medicine techniques aimed at reversing the course of diabetic retinopathy and other blinding eye diseases.

"Our study results bring us a step closer to using stem cells more widely in regenerative medicine, without the historical problems our field has encountered in getting such cells to differentiate and avoid becoming cancerous," says Elias Zambidis, M.D., Ph.D., associate professor of oncology at the Johns Hopkins Kimmel Cancer Center and a member of Johns Hopkins' Institute for Cell Engineering.

Results of experiments using human cells and mice were published online March 5 in Nature Communications.

According to the National Eye Institute, diabetic retinopathy is a leading cause of blindness in U.S. adults. By 2050, researchers estimate that some 14.6 million Americans will have the condition, which results in abnormal blood vessel growth in the retina, where light is processed into vision.

For the study, the scientists began their experiments with a fibroblast -- a connective tissue cell -- taken from a person with type 1 diabetes. Reprogrammed fibroblasts function as "stem" cells, with the potential to give rise to all tissues in the body, including blood vessels.

The Johns Hopkins team, including research associate Tea Soon Park, Ph.D., reprogrammed the fibroblast stem cells to revert to a state that is even more primitive than that of conventional human induced pluripotent stem cells -- more like the state of embryonic cells about six days after fertilization. This is when cells are the most "naive," or more capable of developing into any specialized type of cell with a much higher efficiency than conventional human induced pluripotent stem cells.

To do this, the scientists bathe the cells in a cocktail of nutrients and chemicals. What should go into the cocktail to build a better naive stem cell has been a subject of debate over the past decade.

Zambidis' team used a cocktail mixture of two drugs that other scientists previously used to reprogram stem cells: GSK3β inhibitor CHIR99021, which blocks carbohydrate storage in cells, and MEK inhibitor PD0325901, an experimental anti-cancer drug that can block cancer cell growth. The team had also looked at the potential of a third drug, a PARP inhibitor -- a popular anticancer drug used to treat a variety of cancers including those of the ovaries and breast.

To the researchers' surprise, Zambidis says, the trifecta of MEK, GSK3β and PARP inhibitors worked to wind back the cells' biological clock. He calls the cocktail 3i, named for the three inhibitors. Zambidis' team had first reported experiments using the three-drug cocktail in 2016.

For the new study, the research team tracked the reprogrammed stem cells' molecular profile, including measures of proteins such as NANOG, NR5A2, DPPA3 and E-cadherin that guide cell differentiation. That profile appeared similar to that found in so-called naive epiblast cells, the primitive cells that make up an approximately six day-old human embryo.

The scientists also found that the stem cells reprogrammed with the 3i cocktail did not have abnormal changes in factors that can alter core DNA, called epigenetics, that typically plague other lab-made versions of naive stem cells.

Finally, the research team injected cells called vascular progenitors, which were made from the naive stem cells and are capable of making new blood vessels, into the eyes of mice bred to have a form of diabetic retinopathy that results from blood vessels closing off in the retina. They found that the naive vascular progenitors migrated into the retina's innermost tissue layer that encircles the eye, with higher efficiencies than have been reported with vascular cells made from conventional stem cell approaches. The naive vascular cells took root there, and most survived in the retina for the duration of the four-week study.

"Interestingly, the 3i 'naive reprogramming' cocktail appeared to erase disease-associated epigenetics in the donor cells, and brought them back to a healthy, pristine non-diabetic stem cell state," says Zambidis.

For comparison, the team reprogrammed diabetic fibroblasts to non-naive stem cells using standard methods, and the resulting vascular progenitor cells failed to migrate as deeply into the retina or survive the length of the study.

Zambidis, Park and the other research team members say more experiments are needed to refine the 3i cocktail and to study the regenerative capacity of the stem cells they grow from the cocktail.

Credit: 
Johns Hopkins Medicine

Sticky tape: A key ingredient for mapping artifact origins

image: Artifacts from Kyoden that were sampled for vermilion using sulfur-free adhesive tape. (top and bottom left) Earthenware fragments. (top right) Stone tool. (bottom right) Potsherd. Arrows point to the sampled locations.

Image: 
RIKEN

Researchers at the RIKEN Nishina Center for Accelerator-Based Science in Japan have demonstrated that combining a highly sensitive sulfur analysis technique with simple sulfur-free tape is an effective and harmless way to test extremely small samples of vermilion from artifacts that are thousands of years old. Published in the Journal of Archaeological Science: Reports, the study used this technique to confirm that trade likely existed between Japan's northern island of Hokkaido and the western part of Japan's mainland--a distance of over 1000 miles--more than 3000 years ago.

Vermilion, sometimes called cinnabar, is a bright red mineral that was used in paintings, figurines, statues, ceramics, and ritual ceremonies dating back almost 9000 years across Europe, Asia, and the Americas. The chemical name for vermilion is mercuric sulfide, and small variations in sulfur can distinguish one batch of vermilion from another. Within every vermilion sample, some of the sulfur atoms are standard, while some are isotopes with two extra neutrons. Because the ratio of these atoms does not change over time, it can be used as a fingerprint to identify where the sample came from.

Recently, Kazuya Takahashi and his colleagues in the Astro-Glaciology Research Group developed a highly sensitive method for analyzing sulfur isotope ratios that only requires 1 microgram of vermilion--one millionth of a gram--which is about 500 times smaller than what other methods need. This is important because the smaller the sample, the less damage to the artifacts being tested.

After developing this new technique, Takahashi realized that they needed a way to collect the tiny samples, keeping in mind that the samples need to be burned up to produce sulfur oxide gas during the analysis. The easiest way was to use a tiny 3 mm × 3 mm square of adhesive tape to pick up the vermilion from an artifact. Then, the vermillion and tape could be places into the apparatus and tested. However, most tape contains sulfur, and given the minuscule size of the sample, even the tiniest amount would throw off the results. After trying several different commercial tapes, he got lucky. "By chance, I met an old friend who works in a company that sells different kinds of tape. She knew of one tape that could be sulfur free, which was a great suggestion for me!"

The team tested this polyester adhesive tape as well as two other tapes from local stores. They found that the store-bought tapes contained about 0.5% sulfur, while the special tape did not contain any sulfur. Now they were ready to test the system on real artifacts.

An area in western Japan called Izumo contains an archaeological site with artifacts from a settlement about 3500 years ago. People have speculated that the people of that era traded extensively within Japan. With cooperation from the local government in Izumo, the researchers collected vermilion samples from artifacts excavated from the site and used their highly sensitive analysis technique to determine their sulfur isotope ratios. Then, they compared the sample ratios to the ratios found at eight cinnabar ore mines across Japan. They found that most of the artifacts contained vermilion that was likely mined in the Northern island of Hokkaido, more than 1000 miles away, rather than in closer mines located in western Japan.

Archaeologists often wish to analyze the origins of pigments on wall paintings or pottery, but in many cases, the artifacts are too important to damage even a small amount for sample collection. "Our method might open the doors for new research into ancient trade routes and the history of individual works of ancient art," notes Takahashi.

The precision of the system can still be improved. "Analyzing sample origins using sulfur isotopic ratios is not sufficient at the present time," says Takahashi. "Using ratios from multiple elements can enable us to estimate the origins more precisely than conventional methods can." The team has already started analyzing lead (Pb) and sulfur isotopic ratios of pigment samples from ancient Roman wall paintings found in Spain.

As is often the case, the success of this project relied on technology that was actually created for a totally different purpose. "This is an intriguing application of our isotope analysis technique," notes Yuko Motizuki, director of the Astro-Glaciology Research Group. "But it was originally developed for taking measurements in Antarctic ice cores, which is the main focus of our laboratory.

"We hope archaeologists and research centers around the world can use Takahashi's technique to develop their own measurement systems and continue studying how ancient peoples interacted and traded across continents."

Credit: 
RIKEN

New study presents stretchable and colorless solar cells, using Si microwire composites

image: Freestanding SiMPF after peeling off from the Si parent (scale bar: 100?μm).

Image: 
UNIST

As solar cells become more transparent, you may now add transparent panels of solar cells on windows of buildings and electronic devices to generate electricity. Furthermore, in adding flexibility to this, its product range will be even expanded to assure the future mobile applications for wearable devices.

A research team, led by Professor Kyoung Jin Choi in the School of Materials Science and Engineering at UNIST has introduced a flexible and transparent solar cell, using silicon microwire composites. The new solar cell takes a structure in which cylindrical silicon rods are embedded in a flexible and transparent polymer material. As the visible lights passes between polymer materials without silicon rods, it appears entirely transparent to the human eye. It is also designed to control the sunlight reflected from the silicon rods, thereby increasing efficiency.

When sunlight reaches Earth, the energy is absorbed, transmitted, or reflected. In the case of solar cells, they generate electricity when light is absorbed in their photoactive layers. Whereas, an object that appears to be transparent are when the visible light of solar radiation passes through it. Therefore, making silicon-based solar cells transparent will reduce the amount of solar radiation absorbed, which may actually result in decreasing their efficiency.

To overcome such limitation, Professor Choi's team used transparent and flexible polymer substrates and specially shaped silicon rods. In this solar cell, a silicon rod acts as a photoactive layer, absorbing sunlight and producing electricity. These silicone rods are arranged at intervals which are transparent and invisible to the naked eye. As a result, the new solar cell maintains the transparent and flexible properties of the substrate itself.

In the study, the research team has changed the shape of the SiMW tip dramatically for increased light absorption, while maintaining transparency. With the conventional solar cells, reflection occurs, as well as the absorption and transmission of light. Most of them are unable to take advantage of the reflected light, but the researchers created a structure to absorb it back into the solar cell. Based on the analysis of the light absorption mechanism in the silicon rods, the team designed the light reflected from the top of the bar to be absorbed by the bar next to it.

"This is a new attempt to apply the results of analyzing the theoretical light absorption mechanism to the development of high performance transparent solar cells," says Sung Bum Kang (Combined MS/Phd program in the School of Materials Science and Engineering, UNIST), the first author of the study. "Thus, this recycling structure that reuses has increased the efficiency of the entire solar cell."

"Existing transparent solar cells were manufactured on rigid glass substrates, so their application range was limited," says Professor Choi. "The new solar cell is expected to maintain its initial efficiency of more than 95% even after dozens of bending tests, and be applied to a variety of buildings, vehicle glass, and portable electronic devices."

Credit: 
Ulsan National Institute of Science and Technology(UNIST)

Rejuvenating the immune system supports brain repair after injury

Researchers have identified a major shift in how to treat brain injuries, after rejuvenating immune cells to support the repair process.

The University of Queensland study focused on the brain's learning and memory centre, the hippocampus, and its unique ability to produce new brain nerve cells during adult life, which is critical for learning.

The team used animal models to investigate how the immune system interacts with brain nerve cells after injury and how this influenced the ability to learn and remember.

UQ School of Biomedical Sciences and Queensland Brain Institute researcher Dr Jana Vukovic said up until now, the brain's immune cells, known as microglia, were considered to drive inflammation, resulting in cognitive deficits after injury.

"However, when we removed microglia from mice we were surprised that there was absolutely no change in their behaviour or ability to repair brain tissue," she said.

Dr Vukovic's team then depleted microglia and allowed them to repopulate the brain, finding this profoundly increased brain repair.

"The rejuvenated microglia improved the mice's learning and memory, preserved tissue loss and stimulated the birth of neurons," said Dr Vukovic.

"We have shown that microglia, in part, have been misunderstood and that we need to learn more about how they support and stimulate pathways to promote repair."

Brain injuries impact on a person's ability to concentrate, make decisions, learn and remember, and can range from mild to severe, and be short-term or permanent.

PhD candidate Emily Willis said the findings may lead to the development of therapeutics that alleviate learning and memory deficits associated with a wide range of neurological conditions, such as brain injury and dementia.

"It's no longer about inhibiting microglia's pro-inflammatory elements, it's about finding a way to shift them to a state that supports brain repair," Ms Willis said.

Credit: 
University of Queensland

Low blood pressure linked to high mortality in older adults

that found a link between low blood pressure and higher mortality rates.

A largescale study led by the University of Exeter, published in Age and Ageing and funded by NIHR, analysed 415,980 electronic medical records of older adults in England.

The research was conducted after some countries have changed blood pressure guidelines to encourage clinicians to take measures to reduce blood pressure in a bid to improve health outcomes. UK blood pressure guidelines are within safe parameters for all. However, previous research has not considered the impact on frail older adults, who are often omitted from trials.

The team found that people aged 75 or over with low blood pressure (below 130 / 80) had increased mortality rates in the follow-up, compared to those with normal blood pressure. This was especially pronounced in 'frail' individuals, who had 62 per cent increased risk of death during the ten year follow-up.

Although high blood pressure increased risk of cardiovascular incidents, such as heart attacks, it was not linked to higher mortality in frail adults over 75. Older people aged 85 and over who had raised blood pressure actually had reduced mortality rates, compared to those with lower blood pressure, regardless of whether they were frail or not.

Jane Masoli, a geriatrician and NIHR Doctoral Research Fellow, who led the study as part of her PhD at the University of Exeter, said: "Internationally, guidelines are moving towards tight blood pressure targets, but our findings indicate that this may not be appropriate in frail older adults. We need more research to ascertain whether aggressive blood pressure control is safe in older adults, and then for which patient groups there may be benefit, so we can move towards more personalised blood pressure management in older adults."

She added: "We know that treating blood pressure helps to prevent strokes and heart attacks and we would not advise anyone to stop taking their medications unless guided by their doctor."

Credit: 
University of Exeter

The brain has two systems for thinking about others' thoughts

video: Where does the cat look for the mouse? When the scientists asked the children directly where the cat will search for the mouse, instead of looking at their gaze, 3-year-olds answered incorrectly. Only 4-years-olds succeeded.

Image: 
MPI CBS

In order to understand what another person thinks and how he or she will behave we must take someone else's perspective. This ability is referred to as Theory of Mind. Until recently, researchers were at odds concerning the age at which children are able to do such perspective taking. Scientists at the Max Planck Institute for Human Cognitive and Brain Sciences (MPI CBS), University College London, and the Social Neuroscience Lab Berlin shed new light on this question in a study now published in the renowned journal PNAS. Only 4-year-olds seem to be able to understand what others think. The study reports that this unique ability emerges around 4 years of age because of the maturation of a specific brain network which enables this. Younger children are already capable of predicting others' behaviour based on what they think, but the study shows that this prediction of behaviour relies on a different brain network. The brain seems to have two different systems to take another person's perspective, and these mature at different rates.

The researchers investigated these relations in a sample of 3- to 4-year-old children with the help of a video clips that show a cat chasing a mouse. The cat watches the mouse hiding in one of two boxes. While the cat is away the mouse sneaks over to the other box, unnoticed by the cat. Thus, when the cat returns it should still believe that the mouse is in the first location.

Using eye-tracking technology, the scientists analysed the looking behaviour of their study participants and noticed: Both, the 3- and 4-year-olds expected the cat to go to the box where the mouse had originally been. That is, they predicted correctly where the cat was going to search for the mouse based on the cat's belief.

Interestingly, when the scientists asked the children directly where the cat will search for the mouse, instead of looking at their gaze, 3-year-olds answered incorrectly. Only 4-years-olds succeeded. Control conditions ensured that this was not because the younger children misunderstood the question.

The reason for this discrepancy was a different one. The study shows that different brain structures were involved in verbal reasoning about what the cat thinks as opposed to non-verbal predictions of how the cat is going to act. The researchers refer to these brain structures as regions for implicit and explicit Theory of Mind. These cortical brain regions mature at different ages to fulfill their function. The supramarginal gyrus that supports non-verbal action prediction matures earlier, and is also involved in visual and emotional perspective taking. "This enables younger children to predict how people will act. The temporoparietal junction and precuneus through which we understand what others think - and not just what they feel and see or how they will act - only develops to fulfil this function at the age of 4 years", first author Charlotte Grosse Wiesmann from the MPI CBS explains.

"In the first three years of life, children don't seem to fully understand yet what others think", says co-author Nikolaus Steinbeis from the University College London. "But there already seems to be a mechanism a basic form of perspective taking, by which very young children simply adopt the other's view."

Credit: 
Max Planck Institute for Human Cognitive and Brain Sciences

New imaging technique enables the study of 3D printed brain tumors

TROY, N.Y. -- Glioblastomas are complex, fast-growing malignant brain tumors that are made up of various types of cells. Even with aggressive treatment -- which often includes surgery, radiation, and chemotherapy -- glioblastomas are difficult to treat, leading to an average survival of 11-15 months.

In research published in Science Advances, Xavier Intes, a professor of biomedical engineering at Rensselaer, joined a multidisciplinary team from Northeastern University and the Icahn School of Medicine at Mount Sinai to demonstrate a methodology that combines the bioprinting and imaging of glioblastoma cells in a cost-effective way that more closely models what happens inside the human body.

"There is a need to understand the biology and the complexity of the glioblastoma," said Intes, who is also the co-director of the Center for Modeling, Simulation and Imaging for Medicine (CeMSIM) at Rensselaer. "What's known is that glioblastomas are very complex in terms of their makeup, and this can differ from patient to patient."

To create their 3D tumor cell model, a team, led by Guohao Dai, an associate professor of bioengineering at Northeastern University, made bioinks out of patient-derived tumor cells and printed them along with blood vessels. That vasculature allowed the printed tissue to live and mature, enabling researchers to study it over a matter of months.

The bioprinted blood vessels also provided channels for therapeutics to travel through -- in this case, the chemotherapy drug Temozolomide. In the body, drug delivery to glioblastoma cells is especially complicated because of the blood-brain barrier, a wall of cells that blocks most substances from reaching the brain. Because it can more closely replicate this impediment, the team's method provides a more accurate evaluation of a drug's effectiveness than directly injecting the therapy into the cells.

"That's the unique part of the bioprinting that has been very powerful," Intes said. "It's closer to what would happen in vivo."

In order to see if the therapeutic was making it to the glioblastoma cells and working, Intes and his team developed a specialized technique that could quickly take images of the bioprinted tissue at the cellular level through the thick Plexiglas container in which the tissue was contained -- and could do so using as little light as possible, so as to not damage the cells.

"We developed a new technology that allows us to go deeper than florescence microscopy," Intes said. "It allows us to see, first, if the cells are growing, and then, if they respond to the drug."

This technique, Intes says, could allow researchers to evaluate the effectiveness of multiple drugs at the same time. It is not yet realistic though, he points out, for studying the effectiveness of certain therapeutics on a person's individual tumor because of the short time period in which clinicians often have to provide treatment.

Credit: 
Rensselaer Polytechnic Institute

The complex biology behind your love (or hatred) of coffee

image: A cup of coffee

Image: 
Julius Schorzman/Wikimedia Commons

Why do some people feel like they need three cups of coffee just to get through the day when others are happy with only one? Why do some people abstain entirely? New research suggests that our intake of coffee - the most popular beverage in America, above bottled water, sodas, tea, and beer - is affected by a positive feedback loop between genetics and the environment.

This phenomenon, known as "quantile-specific heritability," is also associated with cholesterol levels and body weight, and is thought to play a role in other human physiological and behavioral traits that defy simple explanation.

"It appears that environmental factors sort of set the groundwork in which your genes start to have an effect," said Paul Williams, a statistician at Lawrence Berkeley National Laboratory (Berkeley Lab). "So, if your surroundings predispose you to drinking more coffee - like your coworkers or spouse drink a lot, or you live in an area with a lot of cafes - then the genes you possess that predispose you to like coffee will have a bigger impact. These two effects are synergistic."

Williams' findings, published in the journal Behavioral Genetics, came from an analysis of 4,788 child-parent pairs and 2,380 siblings from the Framingham Study - a famous, ongoing study launched by the National Institutes of Health in 1948 to investigate how lifestyle and genetics affect rates of cardiovascular disease. Participants, who are all related to an original group from Framingham, Massachusetts, submit detailed information about diet, exercise, medication use, and medical history every three to five years. Data from the study have been used in thousands of investigations into many facets of human health.

Williams used a statistical approach called quantile regression to calculate what proportion of participants' coffee drinking could be explained by genetics - as the study follows families - and what must be influenced by external factors. Past research shows that the most significant environmental factors influencing coffee drinking are culture and geographic location, age, sex, and whether or not one smokes tobacco; with older male smokers of European ancestry drinking the most, overall.

The analysis indicated that between 36% and 58% of coffee intake is genetically determined (although the exact causative genes remain unknown). However, confirming Williams' hypothesis that coffee drinking is a quantile-specific trait, the correlation between a parent's coffee drinking and an offspring's coffee drinking got increasingly stronger for each offspring's coffee consumption quantile, or bracket (for example, zero cups per day, one to two cups, two to four cups, and five or more cups).

"When we started to decode the human genome, we thought we'd be able to read the DNA and understand how genes translate into behavior, medical conditions, and such. But that's not the way it's worked out," said Williams, who is a staff scientist in Berkeley Lab's Molecular Biophysics & Integrated Bioimaging (MBIB) Division. "For many traits, like coffee drinking, we know that they have a strong genetic component - we've known coffee drinking runs in families since the 1960s. But, when we actually start looking at the DNA itself, we usually find a very small percentage of the traits' variation can be attributed to genes alone."

The traditional assumption in genetic research has been that one's surroundings and lifestyle alter gene expression levels in consistent and measurable ways, ultimately creating the outward manifestation - called a phenotype - of a trait. Williams' statistics work shows that the situation is more complex, which helps explain the diversity of traits we see in the real world.

MBIB Division Director Paul Adams commented, "Paul's statistical studies complement the genomics research that Berkeley Lab bioscientists conduct to learn more about the relationship between genes and the environment."

Next, Williams plans to assess whether quantile-specific heritability plays a role in alcohol consumption and pulmonary function. "This is a whole new area of exploration that is just now opening up," he said. "I think it will change, in a very fundamental way, how we think genes influence a person's traits."

Credit: 
DOE/Lawrence Berkeley National Laboratory

Resurrecting ancient protein partners reveals origin of protein regulation

image: In this simulation of two ancient proteins, Aurora A (gray) shifts into a new structure when activated by TPX2 (blue). TPX2 relies on the allosteric networks of Aurora A (pink spheres) to twist it into its new shape.

Image: 
Dorothee Kern/Brandeis University/HHMI

By bringing the ancient history of two proteins back to life, researchers have caught a glimpse into the origin of a billion-year-old molecular partnership.

Biochemist Dorothee Kern and her colleagues reconstructed extinct forms of two cell division proteins, and then watched in the lab as one boosted the activity of the other. What Kern's team observed represents the earliest known instance of two proteins interacting in such a way, the researchers reported February 21 in the journal Science.

That interaction, called allosteric regulation, occurs between many modern proteins, but "how such a feature evolved is unexplored territory," Kern says. Over the eons, allosteric regulation has become an indispensable tool for cells. As cells developed more elaborate networks of protein activity, Kern explains, they needed more nuanced controls to tweak them.

"Allosteric regulation is arguably the biggest evolutionary step in the development of higher organisms," she says.

Kern, a Howard Hughes Medical Institute (HHMI) Investigator at Brandeis University, wants to unravel how proteins and other molecules work together - at atomic resolution and in real time. Pinpointing how proteins behave as they send cellular signals, bind to other molecules, or kickstart chemical reactions could give scientists a new window into drug discovery.

Kern chose to study a protein called Aurora A because it's vitally important in cell division - abnormalities can drive cancer growth - and because it's turned on by a protein partner called TPX2.

During cell division, Aurora A helps to distribute chromosomes equally between daughter cells. TPX2 binds to an "allosteric site" of Aurora A - a spot apart from the active site of the protein. Then, TPX2 brings Aurora A to the site of the action and switches the protein into high gear. Kern wanted to know how the two proteins' partnership evolved.

Organisms across the evolutionary tree make some version of the Aurora A and TPX2 proteins. First, Kern, study coauthor Adelajda Hadzipasic, and their colleagues at Brandeis compared versions of Aurora A and TPX2 from a diverse set of species - including bacteria, plants, and humans. Then, they did a bioinformatics analysis, traveling back in time to deduce the ancient amino acid sequences of the two proteins' oldest common ancestors. Next, they used those sequences to recreate the ancient proteins.

"Evolution used to be speculative subject, but it is now experimental. That's what's really exciting about this technique," says Christopher Miller, an HHMI Investigator alum and recently retired biochemist who used to work next door to Kern at Brandeis.

Experiments in the lab let Kern's team map the proteins' entwined histories. Initially, around 1.5 billion years ago, Aurora A had to self-activate - no TPX2 required. After TPX2 showed up, about a half billion years later, the protein increased Aurora A's productivity by pulling it to the job site. "That created an evolutionary increase in fitness," she says.

Because teaming up with TPX2 boosted Aurora A's efficiency, the partnership endured. That gave the two proteins time to dial in a more sophisticated relationship, Kern says. Over time, TPX2 took on an additional, new role - as Aurora A's activator. Today, the modern Aurora A/TPX2 pair can work 10 times faster than Aurora A alone.

And when Kern's team combined ancient Aurora A with modern TPX2, they found that the two proteins bound together surprisingly well - despite almost a billion years of evolution between them.

That wasn't expected, Kern says. Conventional wisdom held that proteins that work together also evolve together - so a change in one partner is matched by a complementary change in the other. Modern TPX2, the researchers thought, would likely have amassed too many changes to connect with such an ancient partner.

Kern solved this mystery. The sections of Aurora A and TPX2 that touch stayed essentially the same over 1 billion years, her team discovered, even as other parts of the proteins morphed and shifted over time.

Investigating the details of such interactions could provide a springboard for creating new types of drugs, says Neel Shah, a chemist at Columbia University. Though there's a long road between identifying proteins' allosteric sites and actually designing drugs that can take advantage of them, he says, "these findings could be a starting point."

Credit: 
Howard Hughes Medical Institute

Adjustable even and odd harmonic radiation characteristics of crystal target by strain engineering

image: Simulated harmonic spectra of monolayer AlN in a laser field with the peak intensity of 1.0×1012 W/cm2, wavelength of 1600 nm and pulse duration of 5 optical cycles.

Image: 
©Science China Press

As a cutting-edge subject in the cross research field, solid high-order harmonics not only provide a new strategy for high-efficiency, wide energy spectrum, short pulse light source, but also can be used to better study the electronic structure and nonlinear optical properties of condensed matter.

A recent study has revealed the novel harmonic spectrum distribution dependent on crystal orientation by adjusting the strain of single layer AlN, which is entitled "Strain effect on the orientation-dependent harmonic spectrum of monolayer aluminum nitride" and published in SCIENCE CHINA Physics, Mechanics & Astronomy. Prof. Ruifeng Lu from Nanjing University of Science and Technology is the corresponding author.

Using the theoretical model of multi-band semiconductor Bloch equation, the researchers found that the coherent enhancement of different quantum paths of electronic transitions resulted in different odd and even harmonics radiated by the strained target under the action of ultrafast and strong laser. This work provides a reference for the investigation of the electronic structure and dynamics of semiconductor in the strong laser field.

Since the scientists at Stanford University used ZnO crystal as the medium to obtain non-perturbed high-order harmonics in 2011 [1], the study on solid harmonics has attracted extensive interest of world-renowned research groups in related fields. Due to the high atomic density in the crystal materials, it is found that the harmonic signal intensity of SiO2 crystal is significantly higher than that of gas-phase medium under the same driving laser conditions [2]. Also, the solid harmonic signal can be used to reconstruct band structure [3] as well as Berry curvature [4] of crystal. In 2015, the high-order harmonics of GaSe crystal were measured in experiment and the coherence mechanism of quantum paths was proposed [5].

In recent years, Prof. Ruifeng Lu and coworkers have made great progress in the theoretical research of solid harmonics. In 2018, the details of the first solid harmonic experimental data are qualitatively reproduced for the first time, and the generation mechanism of odd and even harmonics derived from crystal spatial symmetry is clarified [6]. In 2019, it is further proved that the mechanisms of transition dipole moment, interband polarization and Berry curvature are essentially self-consistent, which are all the reflection of intrinsic symmetry [7].

At present, researchers try to obtain high-quality high-order harmonic signals by using light field regulation [8] or material regulation [9]. As one of the common methods in condensed matter physics, strain control has not been discussed seriously in previous solid harmonic studies. This work focuses on the material control. It is found that the band gap of monolayer AlN crystal becomes narrow under strain condition, thus the efficiency of the first harmonic plateau (with a cut-off of the 11th order in Figure 1) mainly from the (V1, C1) band pair is obviously enhanced with the odd harmonics still dominant. For the second harmonic plateau (with a cut-off of the 29th order in Figure 1), odd harmonics are dominant along both Γ-M and Γ-K direction without strain, whereas even harmonics are dominant along Γ-M direction when strain is applied. Through the detailed analysis of the transition dipole moment, it is confirmed that the peculiar even harmonics of the second plateau come from the enhanced interference of direct transition (V1-C1) and indirect transition (V1-V2-C1) of valence electron by applying strain. The scheme of controlling the harmonic radiation by changing the electronic structure is of great scientific significance and reference value to the study of high-order harmonic in solid.

Credit: 
Science China Press

The impact of energy development on bird populations

image: Andrew Sulphin -co author- releasing tagged female greater sage-grouse

Image: 
Photos taken by Thomas Maechtle -co author

The greater sage-grouse is an iconic bird that lives in the western United States, and its populations are in decline. A new study published in the Journal of Wildlife Management reveals that energy development has negative impacts on sage-grouse reproduction.

The study's authors note that the full extent of such impacts on reproduction are not always realized because most female sage-grouse choose to nest and raise chicks in less disturbed areas, but only when these areas are still available to them.

The findings indicate that efforts are needed to avoid disturbing sage-grouse habitat when positioning renewable and non-renewable energy projects, and they highlight the complexities of balancing species conservation with energy development demands.

"Our study is unique in that instead of a commonly used metric for development intensity such as density of wells in an area, we delineated the actual footprint of energy development to measure the direct removal of sagebrush habitats for energy infrastructure, across several study areas," said lead author Christopher P. Kirol. "Our findings suggest that reproductive costs incurred by sage-grouse have a direct relationship to the footprint of energy development and this relationship holds irrespective of the type of energy infrastructure, whether natural gas or conventional oil, for example."

Credit: 
Wiley

Endangered species on supermarket shelves

image: Retail eel products found in local grocers, convenient stores and supermarkets.

Image: 
@The University of Hong Kong

Imagine purchasing products from your local grocer, only to find out that those products are comprised of critically endangered species! That's what a team from the University of Hong Kong, Division of Ecology and Biodiversity has recently discovered on Hong Kong supermarket shelves. A team led by Dr David Baker from the University's Conservation Forensics laboratory, has recently published the results from an investigation into European eel products on sale in Hong Kong supermarkets.

The study, published in Science Advances, found that nearly 50% of retail eel products, ranging from fillets to snack items from grocers and convenience stores, contained a critically endangered species of fish. According to the IUCN, The European eel (Anguilla anguilla) is at risk of extinction. For this reason, trade in European eels and their food product derivatives is subject to international regulation under the Convention for the International Trade of Endangered Species (CITES). CITES is meant to ensure that permits are required for their import and export in an effort to regulate trade and foster conservation.

Eel, extremely popular in East Asia and particularly Japan, has traditionally been fished from East Asian populations of the Japanese eel (Anguilla japonica). However, overexploitation due to growing demand from Mainland China and a combination of threats ranging from rising ocean temperatures, parasites, and dammed rivers have led to dramatic declines in eel populations. This is true not only for European and Japanese species, but also for their American and Indo-Pacific relatives.

To satisfy demand for eel in East Asia, juvenile eels (known as glass eels) are caught while swimming upstream in their native range spanning Europe and North Africa, and smuggled to Asia to be raised to maturity. To date, captive breeding of eels has not been economically viable; wild-caught glass eels are thus used to "seed" eel farms. In recent years the illegal trade has been highlighted by a number of high-profile investigations and increasing prosecutions.

"The illegal export of glass eels from Europe to Asia has now been recognised as one of the world's greatest wildlife crimes and Europol has estimated the scale of over 300 million eels (2018 data) annually. The next step is to investigate the global consumer markets to identify where these trafficked eels are eventually consumed. The numbers from Hong Kong are very alarming and reflect the huge amounts of European eels that are being farmed in Asia. It is now up to individual countries to investigate the scale of European eels entering their national food chains illegally." -Florian Stein, Sustainable Eel Group

The international trade in glass eels is incredibly lucrative. One kilogram of glass eels can contain up to 3,500 individuals and has been recorded selling for over HKD$50,000 on the black market. This highly profitable trade has attracted the attention of international criminal syndicates, who smuggle glass eels in suitcases from Europe to Asia for resale. In their juvenile stages, eels are extremely difficult to identify to the species level. The two most common cousins of the endangered European eel (the Japanese and American eel) are not listed in CITES, therefore no permit is required for their trade. Because of the challenges in visual identification, endangered European eels can be laundered along with their legally traded relatives.

Already, the existence of Europe-Asia smuggling routes has been documented, but the ultimate destination of the smuggled eels remained elusive. Originally conceived as an undergraduate project looking at seafood mislabeling, the investigation into European eel took off when students noticed a surprising amount of European eel present in supermarket products.

"The eel project is the most exciting thing I have done during my undergraduate study in HKU. I once thought research was only for postgraduates and professors, but it turns out I, even as a student, was able to do meaningful research that actually made an impact in illegal trading. This has made me more determined to continue work in environmental fields." -Haze Chung, Year 4 Undergraduate Researcher

The study covered a wide range of Hong Kong supermarkets and convenience stores across all districts. Surprisingly, almost 50% of the eel products surveyed were determined to be European eel. The results from this study suggested that large scale smuggling networks trafficking European eels are interwoven with local supplier chains, resulting in endangered species ending up on supermarket shelves, totally unbeknownst to consumers.

Credit: 
The University of Hong Kong

Damaging impacts of warming moderated by migration of rainfed crops

image: Nathan Mueller, assistant professor in the Department of Ecosystem Science and Sustainability at Colorado State University

Image: 
Joe Mendoza/Colorado State University

Many studies seek to estimate the adverse effects of climate change on crops, but most research assumes that the geographic distribution of crops will remain unchanged in the future.

New research using 40 years of global data, led by Colorado State University, has found that exposure to rising high temperatures has been substantially moderated by the migration of rainfed corn, wheat and rice. Scientists said continued migration, however, may result in significant environmental costs.

The study, "Climate adaptation by crop migration," is published March 6 in Nature Communications.

"There's substantial concern about the impacts of climate change on agriculture and how we can adapt to those changes," said Nathan Mueller, assistant professor in the Department of Ecosystem Science and Sustainability at CSU and a senior author on the paper.

"We often think about how farmers can adapt to shifting climate conditions by changing crop varieties or planting dates. But farmers have also been changing what crops they are growing over time, collectively leading to large-scale shifts in crop distribution. This pathway of adaptation has been underexplored."

40 years of data from around the world

Using new, high-resolution datasets on crop areas around the world, the research team analyzed the location of crops, climate, and irrigation from 1973 to 2012. They focused on rainfed crops, since they are highly sensitive to changes in temperature and extreme weather.

"We found that on average, over these cropland areas, things are getting warmer," said Mueller, also a researcher in the CSU College of Agricultural Sciences.

The study showed that exposure to increased high temperatures for corn, wheat and rice was much less than it would have been if the crops were positioned where they were in the 1970s.

CSU postdoctoral fellow and first author Lindsey Sloat said this does not mean there is an unlimited capacity for farmers to adapt to climate change by shifting where they grow crops.

"If you add new farmland, that comes with massive environmental consequences," she said. "Land use change in agriculture is one of the biggest drivers of biodiversity loss, with consequences for carbon storage. We can mitigate some of the effects of climate change by increasing irrigation, but there are also environmental costs on that front."

Researchers also found that unlike the other crops, there has been a huge expansion in the production of soybeans, and that these crops are being grown in hotter areas around the world.

Next steps

Sloat said the research team will next delve into analyzing other climate variables, moving beyond temperature to consider how changes in a harvested area can alter exposure to other extreme climate conditions.

"Since this migration has been extensive enough in the past to substantially alter exposure to climate trends, we need to think about what our agricultural landscapes are going to look like in the future as warming increases," said Mueller.

Credit: 
Colorado State University

Gut bacteria can penetrate tumors and aid cancer therapy, study suggests

image: This diagram shows the immune signaling pathways activated by Bifidobacteria after they migrate into tumors from the gastrointestinal tract. This enhances the response to immunotherapy with anti-CD47 antibodies.

Image: 
Shi et al., 2020

Researchers at the University of Texas Southwestern Medical Center and University of Chicago have discovered that bacteria that usually live in the gut can accumulate in tumors and improve the effectiveness of immunotherapy in mice. The study, which will be published March 6 in the Journal of Experimental Medicine (JEM), suggests that treating cancer patients with Bifidobacteria might boost their response to CD47 immunotherapy, a wide-ranging anti-cancer treatment that is currently being evaluated in several clinical trials.

CD47 is a protein expressed on the surface of many cancer cells, and inhibiting this protein can allow the patient’s immune system to attack and destroy the tumor. Antibodies targeting CD47 are currently being tested as treatments for a wide variety of cancers in multiple clinical trials. But studies with laboratory mice have so far yielded mixed results: some mice seem to respond to anti-CD47 treatment, while others do not.

A team of researchers led by Yang-Xin Fu at the University of Texas Southwestern Medical Center and Ralph R. Weichselbaum, co-director of The Ludwig Center for Metastasis Research at the University of Chicago, found that the response to treatment depends on the type of bacteria living in the animals’ guts.

Tumor-bearing mice that normally respond to anti-CD47 treatment failed to respond if their gut bacteria were killed off by a cocktail of antibiotics. In contrast, anti-CD47 treatment became effective in mice that are usually non-responsive when these animals were supplemented with Bifidobacteria, a type of bacteria that is often found in the gastrointestinal tract of healthy mice and humans. Bifidobacteria have previously been shown to benefit patients with ulcerative colitis.

Surprisingly, however, the researchers found that Bifidobacteria do not just accumulate in the gut; they also migrate into tumors, where they appear to activate an immune signaling pathway called the stimulation of interferon genes (STING) pathway. This results in the production of further immune signaling molecules and the activation of immune cells. When combined with anti-CD47 treatment, these activated immune cells can attack and destroy the surrounding tumor.

“Our study demonstrates that a specific member of the gut microbial population enhances the anti-tumor efficacy of anti-CD47 by colonizing the tumor,” Fu says. “Administration of specific bacterial species or their engineered progenies may be a novel and effective strategy to modulate various anti-tumor immunotherapies.”

“Our results open a new avenue for clinical investigations into the effects of bacteria within tumors and may help explain why some cancer patients fail to respond to immunotherapy,” says Weichselbaum.

Credit: 
Rockefeller University Press