Culture

The gold standard in functional brain imaging for over two decades, functional magnetic resonance imaging (fMRI) has transformed the landscape of research and clinical care. Yet, because of its cost and functional limitations, scientists have continued to look for new ways to see into the human brain.

Researchers from the Keck School of Medicine of USC and the California Institute of Technology (Caltech), with the help of patients recovering from traumatic brain injury, have now demonstrated an alternative way to produce highly detailed images of the human brain. Their work, published in
Nature Biomedical Engineering, yielded the first pictures of human brain function ever produced using functional photoacoustic computerized tomography (fPACT) - a landmark in the history of functional brain imaging.

Technology meets technique

Imaging with fPACT works by emitting a beam of laser light into the area being imaged. The light is absorbed by oxygen-carrying hemoglobin molecules in the patient's red blood cells causing them to vibrate ultrasonically. The vibrations can then be scanned by sensors. Lihong Wang, PhD the Bren professor of medical and electrical engineering at the Andrew and Peggy Cherng Department of Medical Engineering at Caltech is a leader in the field of photoacoustic imaging.

The technology has previously been successful in animal and some human tissue models, but there are hurdles to applying it to the brain. "The human skull is an acoustic lens, but it distorts and attenuates our signals," Wang says. "It's like looking outside through a wavy window. The barrier impacts the clarity of the image rendered, a challenge our field is working to overcome."

Despite the challenges, this research collaboration has shown proof of concept that fPACT can be used for brain imaging. To establish the technology's effectiveness, Charles Liu, MD, PhD, director of the USC Neurorestoration Center and professor of clinical neurological surgery, and Jonathan Russin, MD, an associate director of the USC Neurorestoration Center and assistant professor of clinical neurological surgery, enlisted the aid of traumatic brain injury patients in the USC Neurorestoration Center.

"Our study subjects had undergone hemicraniectomy [the temporary removal of a large portion of the skull], which enabled us to test the technology without interference in fully awake humans prior to skull reconstruction surgery. Thanks to their participation, we discovered fPACT is capable of creating functional brain images that are superior in some ways to 7T fMRI," Liu says. "This may be something that will change neuroimaging forever."

The study subjects were recruited from Rancho Los Amigos National Rehabilitation Center where a large number of cranial reconstruction surgeries are performed. "It is terrific to work with patients to develop transformative tools to better understand how to treat their neurological disabilities", adds Liu, who also serves as chair of neurosurgery and orthopedics and chief of innovation and research at Rancho.

The benefits could be enormous. "fPACT costs less than MRI, is potentially portable, is accessible to patients with implants and eliminates the claustrophobic/magnetic MRI environment," Russin notes. "This study is a first for functional human brain imaging - and, we believe, a critical step forward in advancing the field."

Reactions to results

In order to complete the study, Liu, Russin and Wang solicited critical input from the USC Mark and Mary Stevens Institute for Neuroimaging and Informatics, which provided expertise and resources including access to a state-of-the-art 7-Tesla MRI. "To understand the potential of fPACT, the research team needed to compare it to the best current functional brain imaging," says Danny J.J. Wang, PhD, professor of neurology and radiology. "After reviewing the data, it seems clear that fPACT could have immense impact in neuroscience, with applications ranging from vessel and tumor imaging to localization of function and seizures."

Results from the study highlight fPACT's ability to produce accurate 3D maps of blood flow. Since blood flow increases to specific areas of the brain during cognitive tasks, a device that shows blood concentration and oxygenation changes can help researchers and medical professionals monitor brain activity. This is known as functional imaging.

The study offers key insight into fPACT's long-term potential. Today, Liu, Russin and their team are partnering with Caltech to develop workarounds to skull interference to further investigate the possibilities of fPACT technology.

BONN, 10 June - Unprecedented changes in climate and biodiversity, driven by human activities, have combined and increasingly threaten nature, human lives, livelihoods and well-being around the world. Biodiversity loss and climate change are both driven by human economic activities and mutually reinforce each other. Neither will be successfully resolved unless both are tackled together.

This is the message of a workshop report, published today by 50 of the world's leading biodiversity and climate experts.

The peer-reviewed workshop report is the product of a four-day virtual workshop between experts selected by a 12-person Scientific Steering Committee assembled by the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) and the Intergovernmental Panel on Climate Change (IPCC) - the first-ever collaboration between these two intergovernmental bodies.

The report finds that previous policies have largely tackled biodiversity loss and climate change independently of each other, and that addressing the synergies between mitigating biodiversity loss and climate change, while considering their social impacts, offers the opportunity to maximize benefits and meet global development goals.

"Human-caused climate change is increasingly threatening nature and its contributions to people, including its ability to help mitigate climate change. The warmer the world gets, the less food, drinking water and other key contributions nature can make to our lives, in many regions" said Prof. Hans-Otto Pörtner, co-chair of the Scientific Steering Committee.

"Changes in biodiversity, in turn, affect climate, especially through impacts on nitrogen, carbon and water cycles," he said. "The evidence is clear: a sustainable global future for people and nature is still achievable, but it requires transformative change with rapid and far-reaching actions of a type never before attempted, building on ambitious emissions reductions. Solving some of the strong and apparently unavoidable trade-offs between climate and biodiversity will entail a profound collective shift of individual and shared values concerning nature - such as moving away from the conception of economic progress based solely on GDP growth, to one that balances human development with multiple values of nature for a good quality of life, while not overshooting biophysical and social limits."

The authors also warn that narrowly-focused actions to combat climate change can directly and indirectly harm nature and vice-versa, but many measures exist that can make significant positive contributions in both areas.

Among the most important available actions identified in the report are:

Stopping the loss and degradation of carbon- and species-rich ecosystems on land and in the ocean, especially forests, wetlands, peatlands, grasslands and savannahs; coastal ecosystems such as mangroves, salt marshes, kelp forests and seagrass meadows; as well as deep water and polar blue carbon habitats. The report highlights that reducing deforestation and forest degradation can contribute to lowering human-caused greenhouse gas emissions, by a wide range from 0.4-5.8 gigatonnes of carbon dioxide equivalent every year.

Restoring carbon- and species-rich ecosystems. The authors point to evidence that restoration is among the cheapest and quickest nature-based climate mitigation measures to implement - offering much-needed habitat for plants and animals, thus enhancing resilience of biodiversity in the face of climate change, with many other benefits such as flood regulation, coastal protection, enhanced water quality, reduced soil erosion and ensuring pollination. Ecosystem restoration can also create jobs and income, especially when taking into consideration the needs and access rights of indigenous peoples and local communities.

Increasing sustainable agricultural and forestry practices to improve the capacity to adapt to climate change, enhance biodiversity, increase carbon storage and reduce emissions. These include measures such as diversification of planted crop and forest species, agroforestry and agroecology. Improved management of cropland and grazing systems, such as soil conservation and the reduction of fertilizer use, is jointly estimated by the report to offer annual climate change mitigation potential of 3-6 gigatonnes of carbon dioxide equivalent.

Enhancing and better-targeting conservation actions, coordinated with and supported by strong climate adaptation and innovation. Protected areas currently represent about 15% of land and 7.5% of the ocean. Positive outcomes are expected from substantially increasing intact and effectively protected areas. Global estimates of exact requirements for effectively protected and conserved areas to ensure a habitable climate, self-sustaining biodiversity and a good quality of life are not yet well established but range from 30 to 50 percent of all ocean and land surface areas. Options to improve the positive impacts of protected areas include greater resourcing, better management and enforcement, and improved distribution with increased inter-connectivity between these areas. Conservation measures beyond protected areas are also spotlighted - including migration corridors and planning for shifting climates, as well as better integration of people with nature to assure equity of access and use of nature's contributions to people.

Eliminating subsidies that support local and national activities harmful to biodiversity - such as deforestation, over-fertilization and over-fishing, can also support climate change mitigation and adaptation, together with changing individual consumption patterns, reducing loss and waste, and shifting diets, especially in rich countries, toward more plant-based options.

Some focused climate mitigation and adaptation measures identified by the report as harmful to biodiversity and nature's contributions to people include:

Planting bioenergy crops in monocultures over a very large share of land areas. Such crops are detrimental to ecosystems when deployed at very large scales, reducing nature's contributions to people and impeding achievement of many of the Sustainable Development Goals. At small scales, alongside pronounced and rapid reductions in fossil-fuel emissions, dedicated bioenergy crops for electricity production or fuels may provide co-benefits for climate adaptation and biodiversity.

Planting trees in ecosystems that have not historically been forests and reforestation with monocultures - especially with exotic tree species. This can contribute to climate change mitigation but is often damaging to biodiversity, food production and other nature's contributions to people, has no clear benefits for climate adaptation, and may displace local people through competition for land.

Increasing irrigation capacity. A common response to adapt agricultural systems to drought that often leads to water conflicts, dam building and long- term soil degradation from salinization.

Any measures that focus too narrowly on climate change mitigation should be evaluated in terms of their overall benefits and risks, such as some renewable energies generating surges of mining activity or consuming large amounts of land. The same applies to some technical measures too narrowly focused on adaptation, such as building dams and sea walls. Although important options for mitigating and adapting to climate change exist, these can have large negative environmental and social impacts - such as interference with migratory species and habitat fragmentation. Such impacts can be minimized, for instance, by developing alternative batteries and long-lived products, efficient recycling systems for mineral resources, and approaches to mining that include strong considerations for environmental and social sustainability.

The report authors stress that while nature offers effective ways to help mitigate climate change, these solutions can only be effective if building on ambitious reductions in all human-caused greenhouse gas emissions. "Land and ocean are already doing a lot - absorbing almost 50% of CO2 from human emissions - but nature cannot do everything," said Ana María Hernández Salgar, Chair of IPBES. "Transformative change in all parts of society and our economy is needed to stabilize our climate, stop biodiversity loss and chart a path to the sustainable future we want. This will also require us to address both crises together, in complementary ways."

Highlighting the significance of the co-sponsored workshop, Dr. Hoesung Lee, Chair of the IPCC, said: "Climate change and biodiversity loss combine to threaten society - often magnifying and accelerating each other. By focusing on synergies and trade-offs between biodiversity protection and climate change mitigation and adaptation, this workshop advanced the debate on how to maximize benefits to people and the planet. It also represented an important step in collaboration between our two communities."

"It may be impossible to achieve win-win synergies, or even manage the tradeoffs between climate and biodiversity actions in every single patch of a landscape or seascape," said Prof. Pörtner, "But achieving sustainable outcomes becomes progressively easier when integrating a mix of actions at larger spatial scales, through cross-border collaboration and joint consultative spatial planning, which is why it is important to also address the lack of effective governance systems and mechanisms to improve integration between solutions for climate change and biodiversity."

Curtin University researchers have helped uncover the four billion year old story of a lunar sample brought from the Moon to Earth, by the manned Apollo 17 mission more than 50 years ago.

The global research collaboration, involving scientists from the UK, Canada, Sweden and Australia, aimed to analyse the ancient rock sample through a modern lens to find out its age, which crater it came from and its geological trajectory.

That modern lens was provided, in part, by both Curtin's Geoscience Atom Probe Facility* and Space Science and Technology Centre* (SSTC) where the research team was able to use the most advanced analytical equipment to accurately date the sample and perform sophisticated numerical impact simulations to determine the source crater.

Co-author Associate Professor Katarina Miljkovic from the SSTC in Curtin's School of Earth and Planetary Sciences said Curtin's involvement ensured the international team had access to world-class facilities in order to shed new light about Earth-Moon origins.

"Through a truly international collaborative effort, we have connected a tiny lunar sample investigated on a microscopic scale with the moment when the Moon's surface was smashed by a major impact event. The study showcases the extent of Curtin's analytical and numerical capability to solve complex geological problems on a planetary scale," Associate Professor Miljkovic said.

"Dating techniques (Uranium-Lead geochronology) suggested this sample from the Moon's Serenitatis Basin is very old, around 4.2 billion years- that's only about 350 million years younger than the entire Solar System, making it a precious sample for learning about the Moon's early evolution and our planet's origins.

"The study also provides a new insight into the atomic scale processes that take place in minerals affected by extreme impact events. The analytical work done at Curtin's Geoscience Atom Probe Facility looked at the distribution of atoms in the sample and found that it experienced not one, but two impact events. The second impact transported the sample near to its resting place where it was collected by astronauts."

Numerical impact simulations made at Curtin's Space Science and Technology Centre, supported the analytical findings with detailed understanding of the fate of this sample as it was flung across the Moon during the impact events that caused the craters.

Director of the SSTC, Professor Phil Bland said Curtin is proud to have played an integral part in uncovering this important story which provides an invaluable reference point to understand the entire bombardment history of the Earth-Moon system.

"This research shows that even the tiniest sample brought back from space may yield profound results that advance our understanding of the origins and evolution of Earth and planetary bodies in our Solar System," Professor Bland said.

"It is also an excellent demonstration of the need for more space missions that aim to return samples to Earth, given that the scientific return is enormous."

The research team was led by Dr Ana Cernok from Open University (UK) and also involved the University of Portsmouth (UK), Royal Ontario Museum, University of Toronto and Université de Sherbrooke (Canada) and Swedish Museum of Natural History (Sweden).

Researchers from Curtin also included Professor Steven Reddy, Dr Denis Fougerouse, Dr William Rickard and Dr David Saxey.

Some aspects of the study were supported by the Australia Research Council, the Science and Industry Endowment Fund and The Institute for Geoscience Research (TIGeR).

The full paper, 'Lunar samples record an impact 4.2 billion years ago that may have formed the Serenitatis Basin' was published in Nature Communications Earth and Environment.

Cell viability require that a variety of functions at the cell membrane are maintained properly. P-type ATPases translocate substrates across the membrane, and they have evolved into different types taking care of specific substrates within a diverse range. Now, key structural aspects have been described on how two different types of P-type ATPases - a Ca2+ transporting Ca2+ -ATPase and a lipid transporting P4-ATPase - have adapted to different substrates and physical environments.

Many bacteria export intracellular calcium using active transporters homologous to the well-described mammalian Ca2+-ATPases such as plasma-membrane Ca2+-ATPase and sarco-endoplasmic reticulum Ca2+-ATPase (PMCA and SERCA, respectively). Crystal structures of Ca2+-ATPase 1 from Listeria monocytogenes (LMCA1) suggest that LMCA1 is pre-organized for dephosphorylation upon Ca2+ release, which can explain the rapid dephosphorylation observed earlier in single-molecule studies.

Also, variation in the architecture of the calcium binding sites explains why LMCA1 transports a single Ca2+ ion similar to PMCA, in contrast to two transported Ca2+ ions in SERCA. The LMCA1 structures provide insight into the evolutionary divergence and conserved features of this important class of ion transporters that also inform us on central mechanisms of mammalian Ca2+ -ATPases and how they can be regulated or affected by pathological conditions.

For the P4-ATPase study, researchers took a different perspective. The transport cycle of a P-type ATPase consist of two half-reactions. Phosphorylation where a phosphate is transferred from ATP to the transporter, and dephosphorylation, where the phosphate is again released. In contrast to ion transporters such as LMCA1, the P4-ATPases transport lipids and are known as lipid flippases. Importantly, the lipid transport is coupled to the dephosphorylation reaction of the cycle, where for ion transporting P-type ATPases it is mainly coupled to the phosphorylation reaction.

Through new structures determined by cryo-electron microscopy (cryo-EM) of a yeast lipid flippase, Drs2p/Cdc50p, it was investigated how the lipid flippases have diverged from ion transporters and have adapted the enzymatic mechanism for the "flipped" purpose. Cryo-EM was a critical technique for this study, and multiple structures of the transport cycle could be determined by locking Drs2p/Cdc50p using different inhibitors and electron microscopy data collected at the electron microscopy infrastructure facility at Aarhus University (EMBION).

The two studies have been spearheaded by PhD student Sara Basse Hansen and Postdoc Milena Timcenko - under the supervision of Professor Poul Nissen (and Sara also of Associate Professor Magnus Kjærgaard) - and are being published in Journal of Molecular Biology.

Researchers from Tel Aviv University took part in a new international study proposing an amendment to the widely accepted theory on the extinction of animal species - by moving the focus from the animal's body size to its reproductive capacity. The researchers found gaps and incompatibilities between mammals and amphibians in the relation between body size and extinction risk: Whereas large mammals bear a smaller number of offspring per birth, leading to higher risk of extinction, larger amphibian females lay more eggs, reducing the threat to the species.

The researchers analyzed data from databases on both extinction risks and reproductive capacities of various species of amphibians (e.g., frogs and salamanders). Contributors to the international study included Prof. Shai Meiri from the School of Zoology at the George S. Wise Faculty of Life Sciences at Tel Aviv University, alongside researchers from Queen's University Belfast, Nottingham Trent University, Exeter University, and the University of Lincoln. The paper was published in the scientific journal Global Ecology and Biogeography.

Prof. Meiri explains that the accelerated extinction of biodiversity worldwide is one of the most pressing challenges facing humanity today. Thus, for scientists in an age of global warming and rapid destruction of natural habitats, understanding the factors that drive the process of extinction is a very high priority.

The extinction theory that has prevailed so far in the scientific world claims that larger species are at greater risk of extinction. This approach is supported by the high number of large and familiar animals that are in fact on the verge of extinction, such as rhinos and whales. One contradictory fact, however, not explained by this theory, is that over 40% of the amphibian species, such as frogs, toads, salamanders, and newts, are endangered despite their small body size - in fact more so than any other vertebrate.

While in other animals the number of offspring decreases as the body size increases, this is not true for amphibians. The researchers found that the females of the smaller amphibians, such as rain frogs (Eleutherodactylus), produce fewer offspring per clutch, compared to larger species like the American bullfrog (Lithobates), that lays up to 80,000 eggs every time. Thus, harmful impact on one generation of small amphibians due to the destruction of their natural habitat can drastically reduce their population and increase the threat of extinction.

Prof. Shai Meiri: "Protecting nature begins with basic science, like this study which gives us more tools to understand the processes of extinction. As we learn more and understand these processes better, we can focus our preservation efforts and point to new, untried directions. An emphasis on the number of offspring rather than body size will help us examine which species and/or geographical regions require protection. In this way the present study can provide a basis for more effective activities in the global struggle against biodiversity loss."

Dr. Daniel Pincheira-Donoso, Lecturer in Evolutionary Biology & Macroecology from the School of Biological Sciences at Queen's University: "More babies per clutch or birth means more variety among the babies. To some extent, it is like playing the lottery: the more tickets you play the higher your chances to win. In this case, more numerous and diverse babies increase the chances that at least some can survive the stress of environmental alterations, such as progressive climatic changes."

Even on a good day, DNA is constantly getting damaged.

Nicks, scratches, breaks: the delicate strands that carry life's genetic code take a beating as they jumble about in the course of their work. If left untreated, errors accumulate, with fatal consequences -- such as cancerous tumors -- for the cell and the organism.

This is where two key proteins come to the rescue: PARP -- or poly ADP ribose polymerase -- acts as a marker for a trouble spot, allowing XRCC1 -- or X-ray repair cross-complementing protein 1 -- to zoom in and begin a repair.

This much has been known for some time and was even recognized in the 2015 Nobel prizes for chemistry, resulting in the development of anti-cancer drugs known as PARP inhibitors that work to disrupt the growth of certain types of tumors.

But while these actors had been identified, their precise roles were not clear. Now a team of scientists at Tokyo Metropolitan University, the University of Sussex, and Kyoto University have revealed exactly how XRCC1 does its work.

"PARP turns out to be something of a villain," explains Kouji Hirota at Tokyo Metropolitan. "The spots it marks become 'PARP traps', which left un-repaired lead to disfunction and cell death."

XRCC1 therefore isn't simply repairing DNA, it is disarming PARP traps.

The scientists compared cells lacking the XRCC1 gene with those lacking PARP as well as with still others lacking both proteins. The team discovered that without XRCC1 on patrol, PARP traps accumulate like landmines.

"PARP exerts toxic effects in the cell and XRCC1 suppresses this toxicity," Hirota elaborates.

The team next seeks to delve even further into these processes, aiming to aid in the development of future cancer treatments.

KyotoU's Shunichi Takeda says: "These results indicate that XRCC1 is a critical factor in the resolution of PARP traps and may be a determinant of the therapeutic effect of PARP inhibitors used in the treatment of hereditary breast and ovarian cancer syndromes."

LA JOLLA--(June 10, 2021) In order for cancer to grow and spread, it has to evade detection by our immune cells, particularly specialized "killer" T cells. Salk researchers led by Professor Susan Kaech have found that the environment inside tumors (the tumor microenvironment) contains an abundance of oxidized fat molecules, which, when ingested by the killer T cells, suppresses their ability to kill cancer cells. In a vicious cycle, those T cells, in need of energy, increase the level of a cellular fat transporter, CD36, that unfortunately saturates them with even more oxidized fat and further curtails their anti-tumor functions.

The discovery, published online in Immunity on June 7, 2021, suggests new pathways for safeguarding the immune system's ability to fight cancer by reducing the oxidative lipid damage in killer T cells. Identifying factors like these that cause immune suppression in the tumor microenvironment can lead to the development of novel immunotherapies for cancer.

"We know that tumors are a metabolically hostile environment for healthy cells, but elucidating which metabolic processes are altered and how this suppresses immune cell function is an important area of cancer research that is gaining a lot of attention," says Kaech, senior author and director of Salk's NOMIS Center for Immunobiology and Microbial Pathogenesis. "Our findings uncovered a novel mode of immunosuppression in tumors involving the import of oxidized fats (AKA lipids) in T cells via the cellular fat transporter CD36, which impairs their anti-tumor functions locally."

The burgeoning field of cancer immunometabolism studies how immune cell metabolism is reprogrammed within tumors and driven by alterations in nutrient availability. While scientists know that tumors accumulate fats--and that such accumulation is associated with immune dysfunction--the details of the relationship haven't been clear.

Working with Joseph Witztum's lab at UC San Diego and Antonio Pinto in the Salk Mass Spectrometry Core facility, the team established that tumors contain elevated amounts of several classes of lipid, and oxidized lipids in particular, which are generally found in oxidized low-density lipoproteins (LDLs), commonly considered "bad" fat. They then observed how killer T cells respond to the oxidized LDLs in tumors and found that killer T cells adapted to the tumor microenvironment by increasing CD36 on their surface and ingesting an abundance of oxidized lipids. Working with Brinda Emu's lab at Yale University, they found this process served as a catalyst to drive even greater amounts of lipid oxidation internally in the killer T cells and ultimately repressed their defenses.

Next, the team employed various methods to investigate how CD36 impaired killer T cell function. They created mouse models lacking CD36 on T cells and used antibodies to block CD36. They confirmed that CD36 promoted T cell dysfunction in tumors by increasing oxidized lipid import, which caused greater lipid oxidation and damage within the T cells and triggered the activation of a stress response protein, p38.

"We found that when the T cells get 'stressed out' by oxidized lipids, they shut down their anti-tumor functions," says Shihao Xu, a Salk postdoctoral fellow and the first author on the paper.

The team also found new therapeutic opportunities to reduce lipid oxidation and restore killer T cells' function in tumors through immunotherapy by blocking CD36 with an antibody therapy or by overexpressing glutathione peroxidase 4 (GPX4, a key molecule that removes oxidized lipids in cells).

Importantly, lipid oxidation doesn't just happen in T cells; it also happens in tumor cells, and too much of it can cause cell death. In fact, there is a lot of excitement in cancer research to increase lipid oxidation in tumor cells to a lethal level, but Kaech and her team urge some caution.

"Now that we've uncovered this vulnerability of T cells to lipid oxidation stress, we may need to find more selective approaches to inducing lipid oxidation in the tumor cells but not in the T cells," says Kaech, who holds the NOMIS Chair at Salk. "Otherwise, we may destroy the anti-tumor T cells in the process, and our work shows a few interesting possibilities for how to do this."

Scientists are hoping the RNA of an obscure infection can one day be used like a Trojan horse to deliver life-saving treatments to citrus trees.

The infection, citrus yellow vein disease, was discovered 64 years ago in Riverside and has never been seen elsewhere in the world. Decades later, UC Riverside researchers have finally unraveled the associated pathogen's genetic codes -- a significant step toward harnessing its unique properties.

A paper describing this work was published recently in the journal Frontiers in Microbiology. It opens the door to testing whether this apparently benign infection could be used as a vehicle to transport antibacterial and antiviral agents into citrus plants' vascular systems, where infections usually take place.

Citrus crops face a highly uncertain future due to Huanglongbing, also known as citrus greening disease. In the past decade, the disease has caused a 72% decline in oranges used for juice, and a 21% decrease in the American fresh citrus fruit market. Growers in other parts of the world are similarly affected, and it continues to spread unabated.

Though there are promising treatments and disease-resistant hybrids being developed for Huanglongbing, none are yet commercially available.

Cells use RNA to convert the information stored in DNA into proteins that carry out different functions. Yellow vein disease is associated with small, independently mobile RNA, called iRNA, which spreads through a plant's vascular system. This spreading mechanism could be a new way to send treatments for Huanglongbing or other diseases into plants.

The story of this promising research starts in 1957 with Lewis Weathers, a UC Riverside plant pathology professor.

"He found four limequat trees with beautiful, bright veins on their leaves, almost fluorescent yellow," said Georgios Vidalakis, a plant pathology professor at UCR, UC-ANR cooperative extension specialist, and principal investigator on the new paper.

"That color was recognized as a disease, and samples of it were deposited at the Citrus Clonal Protection Program disease bank where it was waiting for us to study decades later," Vidalakis said.

Based on Weathers' experiments, it did not appear as though the disease is carried by any animal or other microorganism, Vidalakis said.

"We think it was introduced into the limequats in a single event, and once those plants were destroyed, it never spread to other citrus in California."

Researchers have learned, however, how the disease spread between cells in infected plants. The iRNA disguises itself with plant proteins that lets it pass through cellular connective tissue. This ability to travel inside citrus trees may allow the iRNA to send protective molecules into noncitrus plants as well, including grapes, olives, and cacao.

Yellow vein disease iRNA is also surprisingly small, even for a microscopic organism. Plant viruses typically have four to 10 genes on an average, each with at least one function. The iRNA of this disease has only one functional gene.

"The iRNA is amazing because it's able to manipulate plant cells to help it replicate, despite having only one functional gene," explained Kiran Gadhave, a UCR microbiologist, corresponding author of the paper, and lead researcher of the iRNA project. "In addition to its potential therapeutic value, it's just a scientific curiosity. This is as small as it gets."

Though they believe the pathogen to be benign, the research team is doing additional testing to make sure it won't affect fruit quality or quantity, tree height, or any other markers of health. Symptoms in greenhouse-grown trees were mild. Now this is being tested in a field trial in the living laboratory at the UCR Agricultural Experiment Station AgOps.

"The support of the Citrus Research Board and our close collaborations with the University of Maryland and Silvec Biologics are proving to be crucial in taking this technology from lab to the farm," Gadhave said.

One day, iRNA could be used alongside gene editing technologies like CRISPR, in which cells are trained to recognize and destroy nucleic acids from invading plant pathogens. There are challenges with both methods that need to be overcome first, like managing unintended effects, costs, and efficient delivery.

"The common limitations of both approaches can be overcome by matching their strengths, the same way we integrate different disease management solutions," Gadhave said.

This targeted control of phages provides entirely new biotechnological and therapeutic approaches, e.g. for phage therapies. The results produced in the context of an ERC grant have been published in the Journal of the American Chemical Society.

The human body and its microbiota harbour a large amount of phages. These infect bacteria as virus particles to ensure their own survival. One of their strategies is to integrate into the bacterial genome and multiply via bacterial cell division. However, external signal molecules can trigger the phages' sudden awakening from their dormant stage. Once activated, they destroy their host, the bacterium, and thus release their newly produced viral particles. With a prestigious ERC Consolidator Grant of the European Research Council, Thomas Böttcher investigates the switch from the sleeping (lysogenic) to the activated (lytic) lifestyle of phages.

Warfare between microbes

"We already know that phages decisively influence the population dynamics of bacteria and that microorganisms compete by using chemical weapons," says Thomas Böttcher, Professor of Microbial Biochemistry of the Faculty of Chemistry and the Centre of Microbiology and Environmental Systems Science. "We now wanted to investigate whether, in the complex microbial ecosystems, there are also microbes that specifically activate phages in order to use them against their competitors."

Indeed, the researchers could show that the bacterium Pseudomonas aeruginosa produces large amounts of a signal molecule that triggers the conversion of a phage, residing in a strain of the species Staphylococcus aureus, from a quiet companion into a deadly parasite.

Highly selective phage activation

"We were completely surprised to find that the chemical compound pyocyanin, which we were able to isolate and synthesise, only specifically activated one of several phages of Staphylococcus aureus. Pyocyanin is therefore a highly selective agent," says co-author Magdalena Jancheva.

The drug mitomycin C induces DNA damage in bacterial cells and causes phages to leave their dying host, but according to Thomas Böttcher, "it activates all phages in the bacteria in a non-selective manner". The researchers also observed that pyocyanin releases even more phages in Staphylococcus aureus than mitomycin C, pyocyanin therefore had an "remarkably strong effect".

Discovery provides new perspectives

The bacterial species Pseudomonas aeruginosa and Staphylococcus aureus occupy the same ecological niche in the human body. As pathogens, they frequently occur in the lungs of patients with cystic fibrosis, a congenital metabolic disease. Staphylococcus bacteria dominate at a young age, while Pseudomonas bacteria become more prevalent with increasing age.

The current study demonstrates the efficiency of activation of latent phages by chemical signaling agents in the battle for space and resources between bacterial strains. It provides the first evidence that chemical signaling agents can exhibit selectivity for specific phages in a polylysogenic bacterial strain. Here, the activated phage (phiMBL3) revealed a previously unknown molecular switch through which the signaling agent acts.

"Certain signaling molecules could make it possible to combat pathogens via phage activation - they could thus be used to initiate internal phage therapy," Thomas Böttcher states. At the same time, the phages' molecular switches, which selectively trigger the production of viral particles through a signaling molecule such as pyocyanin, could also serve as a new tool for biotechnology or synthetic biology. "Our findings open up a wide field in which we want to move forward", the researchers conclude.

Recently, a research group led by CHU Yannan and HUANG Chaoqun from the Institute of Health & Medical Technology of the Hefei Institutes of Physical Science (HFIPS) developed an effective method for on-site detection of methamphetamine (MA) in the presence of nicotine by a homemade ion mobility spectrometry. Relevant results were published in Analytical and Bioanalytical Chemistry.

MA is a highly addictive stimulant that affects the central nervous system. The on-site rapid detection of trace amounts of MA and screening illicit drugs in clandestine laboratories are important for drug enforcement agencies and the forensic community in general. However, detecting MA in the presence of nicotine by the frequently used ion mobility spectrometry method is difficult.

In this research, the researchers optimized the temperature of the drift tube and the concentration of the pyridine. It was shown that the best temperature of the drift tube to distinguish MA from nicotine was about 100 ?, when the concentration of doped pyridine was 18 ppm.

The new instrument developed by the team proved effective. "We used pyridine as a dopant," said Prof. HUANG, who conducted this research, "the doped pyridine can eliminate the interference of nicotine, resolve the overlapping spectral peaks of MA and nicotine, and offer a high selectivity and a low limit of detection (LOD) when detecting MA from nicotine."

Further experiment proved that no matter how high the nicotine content was, the interference of nicotine could always be eliminated in the detection of MA using the new method.

These promising results provide a practical method for on-site detection of MA.

Lack of water, floods, or crop losses: As a result of climate change, pronounced periods of drought and rainfall are occurring more frequently and more intensively all around the world, causing human suffering and major economic damage. The more precise seasonal forecasts for the coming months are, the more effectively these consequences can be mitigated. A research team from Karlsruhe Institute of Technology (KIT) has now been able to improve global forecasts using statistical methods so that they can be used on the regional level. The researchers describe the new approach and the economic benefits of seasonal forecasts in the journals Earth System Science Data and Scientific Reports.

One of the consequences of global warming relates to more frequent and more intense periods of drought or precipitation which are now causing major problems worldwide - for example in the supply of food, energy, or drinking water. Improved seasonal meteorological forecasts can be very helpful here: "If we are able to predict rainfall amounts and temperatures more accurately for the weeks and months to come, local decision makers can, e.g., more proactively plan and manage reservoirs or seed selection for the planting season. In this way, they can reduce damage and losses," says Professor Harald Kunstmann who works at the Institute of Meteorology and Climate Research - Atmospheric Environmental Research (IMK-IFU), KIT Campus Alpin, in Garmisch-Partenkirchen and at the University of Augsburg. Using statistical methods, he and his team have now been able to derive local forecasts from global climate models that are significantly more precise than the seasonal forecasts available to date. The researchers developed this method within the framework of an international project called "Seasonal Water Resource Management in Arid Regions" (SaWaM for short), which was funded by the German Federal Ministry of Education and Research (BMBF) and has now been completed.

Regionalized Global Forecasts with Local Relevance

Until now, only global climate models have been available in most cases when it comes to deliver regional forecasts over an average period of weeks or months. "For high-resolution seasonal forecasts, however, these models in their basic form are actually not suitable at all," explains Dr. Christof Lorenz from the Campus Alpin of KIT, who is a co-developer of the new method. The reasons for this are, among others, inconsistencies between forecasts that use different start times and deviations from climatological reference data due to model errors. "Thanks to the statistical correction and regionalization procedures we developed, we can now derive seasonal forecasts that are many times more accurate," says Lorenz. In the regions studied, such as Sudan, Ethiopia, Iran, northeastern Brazil, Ecuador, Peru, and West Africa, the new method enabled the researchers to predict abnormal heat and drought periods up to seven months in advance - with better results than ever before.

Thanks to their extreme precision for preparing seasonal forecasts, the new methods can now be put to practical use. "In particular, by providing early warning of wet or dry periods with an above-average extent, the improved forecast allows to initiate local measures to minimize damage in due time," explains Tanja Portele, a participating climate researcher who works at the Campus Alpin of KIT and at the University of Augsburg. The scientists were able to demonstrate the economic relevance of their approach by using climate data from several decades. "We've shown that seasonal drought forecasts when used in practice can save up to 70 percent of the costs, which would have been theoretically possible with a computationally determined best practice." For the large Upper Atbara Dam in Sudan, the scientists performed an exemplary quantification of the exact savings potential for a drought year. It amounts to $ 16 million.

KIT Methods in Use Worldwide

The new methods for more accurate seasonal forecasting are particularly important for semi-arid regions where the rainy season is limited to a few months of the year. "Here, the water usually has to be stored in reservoirs," Kunstmann says. "For its use, conflicting goals might arise between agriculture, the energy sector, and drinking water supply." Therefore, weather services and official institutions from Sudan and Iran have already adopted the new statistical methods from KIT in order to be able to base their local actions on sound knowledge. Moreover, even for regions that were rarely affected in the past, seasonal forecasts with higher precision are becoming increasingly relevant due to climate change. "So the method will also be used for drought forecasts in Germany in the future," the climate researcher adds.

The annual number of new HIV infections among men who have sex with men (MSM) in England is likely to have fallen dramatically, from 2,770 in 2013 to 854 in 2018, showing elimination of HIV transmission by 2030 to be within reach - suggests work by researchers from the MRC Biostatistics Unit at the University of Cambridge and Public Health England (PHE), published in The Lancet HIV.

To manage the HIV epidemic among MSM in England, enhanced testing and earlier treatment strategies were scaled-up between 2011 and 2015 and supplemented from 2015 by pre-exposure prophylaxis (PrEP). The researchers examined the effect of these interventions on the number of new infections and investigated whether the United Nations (UN) targets for HIV control and elimination of HIV transmission by 2030 might be within reach among MSM in England.

A complexity in this assessment is that HIV infections are not observed. Routine surveillance collects data on new HIV diagnoses, but trends in new diagnoses alone can be misleading as they can represent infections that occurred many years previously and depend on the testing behaviour of infected individuals.

To estimate new HIV infections among adult MSM (age 15 years and above) over a 10-year period between 2009 and 2018, the researchers used a novel statistical model that used data on HIV and AIDS diagnoses routinely collected via the national HIV and AIDS Reporting System in England, and knowledge on the progression of HIV. Estimated trends in new infections were then extrapolated to understand the likelihood of achieving the UN elimination target defined as less than one newly acquired infection per 10,000 MSM per year, by 2030.

The peak in the number of new HIV infections in MSM in England is estimated to have occurred between 2012 and 2013, followed by a steep decrease from 2,770 new infections in 2013 to 1,740 in 2015, and a further steadier decrease from 2016, down to 854. The decline was consistent across all age groups but was particularly marked in MSM aged 25-34 years, and slowest in those aged 45 years or older. Importantly, this decrease began before the widespread roll-out of PrEP in 2016, indicating the success of testing and treatment as infection prevention measures among MSM in England.

Through extrapolation, the researchers calculated a 40% likelihood of England reaching the UN elimination target by 2030 and identified relevant age-specific targeting of further prevention efforts (i.e., to MSM aged ?45 years) to increase this likelihood.

Senior author, Professor Daniela De Angelis, Deputy Director of the MRC Biostatistics Unit, University of Cambridge, said:

"This is very good news and suggests that prevention measures adopted in England from 2011 have been effective. With the rollout of PrEP, England looks on course to meet the goal of zero transmissions by 2030. Our study also shows the value of regular estimation of HIV incidence to recognise and respond appropriately to changes in the current downward trend. The challenge now is to achieve these reductions in all groups at risk for HIV acquisition."

Valerie Delpech, Head of National HIV Surveillance at Public Health England, said:

"We have made good progress towards ending HIV transmission by 2030 in England. Frequent HIV testing and the use of PrEP amongst people most at risk of HIV, together with prompt treatment among those diagnosed, are key to ending HIV transmission by 2030.

"You can benefit from life-saving HIV treatments if you are diagnosed with HIV and it also means you cannot pass the virus on.

"HIV and STI tests are still available through sexual health clinics during the COVID pandemic. Many clinics offer online testing throughout the year - people can order tests on clinic websites, take them in the privacy of their own home, return by post and receive results via text, phone call or post."

Plants use numerous mechanisms for their pollination. Now botanists have discovered a particularly sophisticated system among pipevines that is based purely on deception.

The flowers of the Greek plant Aristolochia microstoma emit a foul, musty scent that seems to mimic the smell of decaying insects. The fly pollinators from the genus Megaselia likely get attracted to this odor while searching for arthropod corpses to potentially mate over and lay their eggs. Then, when entering the tube of an Aristolochia flower, the flies are guided by downward-pointing hairs into a small chamber, which holds the female and male floral organs. Trapped inside, they deposit pollen they carry onto the stigma, before the stamens ripen and release pollen on the body of the flies. When the hairs that block the entrance to the chamber wither, the pollinators can escape, and a new cycle can begin.

"Here we show that the flowers of A. microstoma emit a highly unusual mix of volatiles that includes alkylpyrazines, which are otherwise rarely produced by flowering plants. Our data suggest that this is the only plant species known so far to deceive pollinators attracted to the smell of dead and rotting arthropods, rather than vertebrate carrion," says corresponding author Prof Stefan Dötterl, the head of the plant ecology group and the Botanical Garden at the Paris-Lodron University of Salzburg, Austria.

Between 4-6% of flowering plants are deceptive: they use odor, color, and / or tactile signals to advertise a reward to pollinators, such as nectar, pollen, or mating and breeding sites, but do not actually give this reward. The deception works because pollinators are poor at distinguishing between the reward and the mimic. Deceptive pollination is typical of many orchids, but has also independently evolved many times in other plants, including the genus Aristolochia.

"Aristolochia contains over 550 species spread around the world, especially in tropical and subtropical areas. Aristolochia species are mostly woody vines and herbaceous perennial plants with spectacular, complex flowers that temporarily imprison their visitors for pollination purposes", explains Prof Christoph Neinhuis, co-author of the study, who cultivates one of the largest Aristolochia collection worldwide at the Botanical Garden of TU Dresden.

"Many Aristolochia are known to attract flies with floral scents, for example mimicking the smell of carrion or feces of mammals, decaying plants, or fungi," says Thomas Rupp, first author of the study. "But our curiosity was piqued by A. microstoma, a small herb known only from Greece: unlike other Aristolochia with their colorful, showy flowers, A. microstoma has inconspicuous brownish flowers that lie horizontally - close to the ground or partly buried, among leaf litter or between rocks."

"A. microstoma flowers emit a simple but highly unusual mix of scents that includes 2,5-dimethylpyrazine, a molecule that does not occur in vertebrate carcasses or feces, but in dead beetles. The unpleasant, carrion-like scent can be noticed by people even at a short distance," concludes botanist Prof. Stefan Wanke from TU Dresden.

It eventually became a Nobel prize-winning revolution when researchers first engineered CRISPR as a gene editing technology for bacterial, plant, animal and human cells. The potential of the technology is great and span from curing genetically disposed diseases to applications in agricultural and industrial biotechnology, but there are challenges.

One such challenge consists of selecting a so-called gRNA molecule which should be designed to guide the Cas9 protein to the right location in the DNA where it will make a cut in relation to the gene editing.

"Typically, there are multiple possible gRNAs and they are not all equally efficient. Therefore, the challenge is to select the few that work with high efficiency and that is precisely what our new method does," says Yonglun Luo, Associate Professor Department of Biomedicine at Aarhus University.

The new method is developed from the researchers' new data and implementation of an algorithm, which gives a prediction on what gRNAs that work most efficiently.

"By combining our own data with publicly available data and including knowledge on the molecular interactions between gRNA, DNA and the CRISPR-Cas9 protein, we have succeeded in developing a better method," says Jan Gorodkin, professor at the Department of Veterinary and Animal Sciences at the University of Copenhagen.

Data, deep learning molecular interactions

Jan Gorodkin's research group with Giulia Corsi and Christian Anthon have collaborated with Yonglun Luo's research group in order to achieve the new results. The experimental part of the study was conducted by Luo's group while Gorodkin's group spearheaded the computer modelling.

"In our study, we have quantified the efficiency of gRNA molecules for more than 10.000 different sites. The work was achieved using a massive, high throughput library-based method, which would not be possible with traditional methods," says Yonglun Luo.

The researchers took their starting point concerning data generation in the concept of having a virus express gRNA and a synthetic target site in one cell at a time. The synthetic target sites have exactly the same DNA sequences as the corresponding target sites in the genome. Thus, these synthetic target sites are used as so-call surrogate target sites to capture the CRISPR-Cas9 editing efficiency. Together with colleagues from Lars Bolund Institute of Regenerative Medicine in BGI-Research and Harvard Medical School, they generated high quality CRISPR-Cas9 activity for over 10,000 gRNAs.

With this dataset of gRNAs with known efficiencies from low to high, the researchers were able to construct a model that could predict efficiencies of gRNAs which has not been seen before.

"In order to train an algorithm to become precise, one has to have a large dataset. With our library of viruses, we have obtained data that constitutes the perfect starting point for training our deep learning algorithm to predict the efficiency of gRNAs for gene editing. Our new method is more precise than other methods currently available," says Jan Gorodkin.

Using a new 3D printing process, University of Nottingham researchers have discovered how to tailor-make artificial body parts and other medical devices with built-in functionality that offers better shape and durability, while cutting the risk of bacterial infection at the same time.

Study lead, Dr Yinfeng He, from the Centre for Additive Manufacturing, said: "Most mass-produced medical devices fail to completely meet the unique and complex needs of their users. Similarly, single-material 3D printing methods have design limitations that cannot produce a bespoke device with multiple biological or mechanical functions.

"But for the first time, using a computer-aided, multi-material 3D-print technique, we demonstrate it is possible to combine complex functions within one customised healthcare device to enhance patient wellbeing."

The hope is that the innovative design process can be applied to 3D-print any medical device that needs customisable shapes and functions. For example, the method could be adapted to create a highly-bespoke one-piece prosthetic limb or joint to replace a lost finger or leg that can fit the patient perfectly to improve their comfort and the prosthetic's durability; or to print customised pills containing multiple drugs - known as polypills - optimised to release into the body in a pre-designed therapeutic sequence.

Meanwhile, the aging population is increasing in the world, leading to a higher demand for medical devices in the future. Using this technique could improve the health and wellbeing of older people and ease the financial burden on the government.

How it works

For this study, the researchers applied a computer algorithm to design and manufacture - pixel by pixel - 3D-printed objects made up of two polymer materials of differing stiffness that also prevent the build-up of bacterial biofilm. By optimising the stiffness in this way, they successfully achieved custom-shaped and -sized parts that offer the required flexibility and strength.

Current artificial finger joint replacements, for example, use both silicone and metal parts that offer the wearer a standardised level of dexterity, while still being rigid enough to implant into bone. However, as a demonstrator for the study, the team were able to 3D-print a finger joint offering these dual requirements in one device, while also being able to customise its size and strength to meet individual patient requirements.

Excitingly, with an added level of design control, the team were able to perform their new style of 3D-printing with multi-materials that are intrinsically bacteria-resistant and bio-functional, allowing them to be implanted and combat infection (which can occur during and after surgery) without the use of added antibiotic drugs.

The team also used a new high-resolution characterisation technique (3D orbitSIMS) to 3D-map the chemistry of the print structures and to test the bonding between them throughout the part. This identified that - at very small scales - the two materials were intermingling at their interfaces; a sign of good bonding which means better device is less likely to break.

The study was carried out by the Centre for Additive Manufacturing (CfAM) and funded by the Engineering and Physical Sciences Research Council. The complete findings are published in Advanced Science, in a paper entitled: 'Exploiting generative design for 3D printing of bacterial biofilm resistant composite devices'.

Prior to commercialising the technique, the researchers plan to broaden its potential uses by testing it on more advanced materials with extra functionalities such as controlling immune responses and promoting stem cell attachment.