Tech

Osaka, Japan -- The current COVID-19 climate has made vaccines, antibodies, and immune responses topics of everyday conversation. Now, it isn't just immunologists who want to know how our bodies respond to re-infections months, years, or sometimes decades after an initial immune response. A new study by Tomohiro Kurosaki at Osaka University shows that this ability requires Bach2, a protein that regulates the expression of genes needed to instruct activated B cells under selection to become memory B cells.

Like most biological processes, immune responses are complicated. They involve numerous types of cells and proteins, performing precise step-by-step processes. And of course, we don't know all of them yet. For example, memory B cells are a type of white blood cell that are created in lymph nodes or spleens during an infection. They stick around for years and allow rapid and strong antibody-related responses to re-infection by the same virus or bacteria. In contrast, plasma cells are much more numerous and help during an initial infection by producing antibodies, although they too can exist for long periods of time in the body. Kurosaki and his team focused their research on understanding what causes activated B cells, called germinal center B cells, to become memory B cells, plasma cells, or to be recycled.

Scientists can identify different types of B cells by markers—certain proteins—that they express. On the basis of specific markers, the researchers identified a subset of B cells that they determined were prone to become memory B cells, which they called pro-memory B cells. They then examined mice lacking the protein Bach2, a transcription factor required for memory B cell production. These mice are known to be deficient in producing memory B cells. The researchers found that the lack of Bach2 was associated with fewer pro-memory B cells and increased expression of genes related to a protein complex called mTORC1.

Further testing showed the importance of mTORC1. "We ultimately found that mTORC1 signaling was less active in pro-memory B cells than in those that ended up being recycled," says Kurosaki. Inhibiting mTORC1 activity (in other words, inducing a state of mTORC1 hypometabolism) in the Bach2 knockout mice rescued them, allowing the mice to produce memory B cells. Additionally, in wild-type mice, artificially reducing mTORC1 activity in B cells led to the production of more memory B cells than normal, while increasing its activity had the opposite effect. However, mTORC1 activity alone could not explain everything. Experiments showed that the unique combination of Bach2 expression and reduced mTORC1 activity is necessary to become memory B cells.

Understanding the process through which memory B cells are produced means that this process can be manipulated for our benefit. "Given the importance of memory B cells in protecting us against re-infection, being able to induce their production could be helpful for developing efficient vaccines that remain effective for years," says Kurosaki.

Coherent extreme ultraviolet (XUV) and soft x-ray radiation are very powerful in studying various material properties in biology, chemistry, and physics. Synchrotron radiation (SR) and X-ray free electron laser (XFEL), which are based on large-scale particle accelerators, are developed as multiuser facilities providing XUV~ x-ray radiation. Although SR allows multi-port operation with a MHz repetition rate, the pulse duration is several tens of ps with no temporal coherence. While XFEL can provide high intensity fs XUV pulse, multi-port and high-repetition rated operations are limited.

The high-order harmonic (HH) pulse of an intense femtosecond laser generated upon its interaction with a gas medium has been expected to be another coherent XUV light source, filling a gap between SR and XFEL with much more compact size. During the last two decades, the development of HH source has progressed remarkably, strongly supported by the progress of the intense femtosecond laser technology. However, the repetition rate of the HH pulse, limited by the repetition rate of the fundamental laser system, is still insufficient for novel applications, such as ultrafast XUV spectroscopy, photoelectron spectroscopy, and coincidence measurements.

In a new paper published in Light Science & Application, a team of scientists, led by Dr. Katsumi Midorikawa from RIKEN Center for Advanced Photonics, Japan, and co-workers has developed a novel ultrafast coherent light source in the extreme ultraviolet (XUV) wavelength region with multi-MHz range repetition rates by utilizing intracavity HHG in a Yb:YAG thin-disk mode-locked oscillator.

To date, the highest repetition rates of existing HH XUV light sources have usually been limited to less than 100 kHz. This is due to the fact that a huge average power of more than 1 kW (~1 mJ pulse energy & ~1 MHz repetition rate) of the driving fundamental femtosecond pulses is typically required for realizing such a specification. To overcome this difficulty, we took a unique approach.

The system is based on HHG inside the cavity of a high-energy mode-locked ring oscillator with a repetition rate of 3 MHz adopting an Yb:YAG thin disk laser as a gain medium. A schematic diagram of the system is shown in Figure a. The first breakthrough in the XUV source we developed is that the laser intensity in the cavity is sufficiently high to saturate the highest cutoff photon energy of HHG from an Ar gas target with a high degree of ionization. Technical challenges to achieving high-intensity pulses inside the cavity, such as the careful design of a 100-m-long ring cavity and the cooling system of optics in a vacuum chamber (see Figure b), led to stable long-term operation. A repetition rate of 3 MHz, which is desired for avoiding HHG degradation caused by cumulative ionization effects of gas targets, is sitable for the potential applications. The second point is the multiport HHG. We simultaneously obtained the HHG from a Ne gas target and that from an Ar gas target injected in two different foci in the cavity. This is due to the robustness of the mode-locked oscillator against the nonlinear phase shifts in the target gas media compared with enhancement cavities used for HHG, which is generally fragile against perturbations. We expect to increase further the number of HHG ports by careful dispersion management of the fundamental pulse and enhancement of target gas evacuation capacity in the cavity.

Future developments of gain medium with broader gain bandwidth, for example, Yb:Lu2O3 or Yb:CALGO, would enable shorter pulse duration and enhance HHG efficiency. Besides much higher power operation would be obtained by using zero-phonon line pump lasers and compensation of heat deformation of thin disk wave plane with deformable mirrors. Furthermore, the decrease of laser output coupling would improve a wall-plug efficiency, because this scheme needs no laser output from the cavity in principle. Our method paves the way to MHz repetition-rate high-power XUV sources for multi-user or multi-color facility and should contribute to ultrafast XUV spectroscopy in material science.

According to EU Science Hub, increasingly frequent extreme weather events will cause intensifying damage to infrastructure, with losses estimated to reach €20 billion annually by 2030. These pressing threats bring into sharp focus the need for new answers to the problem of soil stabilization.

Scientists at EPFL's Laboratory of Soil Mechanics (LMS) have developed a number of sustainable solutions, including one that uses enzyme metabolism. Although these methods work for a wide range of soil types, they are considerably less effective when it comes to clay soils. In a paper published today in Scientific Reports, the team demonstrates how chemical reactions can be enhanced by using a battery-like system to apply electric current.

A new type of biocement - produced in situ and at ambient temperature - has recently been put forth as a promising method for stabilizing various soil types. The method harnesses bacterial metabolism to produce calcite crystals that durably bond soil particles together. This biogeochemical process is energy-efficient and cost-effective, and could be rolled out quickly in the coming years. But since the ground needs to be impregnated for the method to work, it is less suited to low-permeability clay soils. Now, the LMS team has developed and successfully tested a viable alternative, which involves applying electric current using sunken electrodes.

"Our findings show that this geoelectrochemical system does indeed influence key stages of the calcification process, especially the formation and growth of the crystals that bind the soil together and enhance its behavior," says Dimitrios Terzis, a scientist at LMS and one of the co-authors of the paper.

The biocement is formed by introducing chemical species into the soil. These include dissolved carbonate and calcium ions, which carry opposite charges. Sunken anodes and cathodes are used to create an electric field, much in the same way as a giant battery. The current forces the ions to move across the low-permeability medium, where they intersect, mix together and eventually interact with soil particles. The result is the growth of carbonate minerals, which act as links or "bridges" that enhance the mechanical performance and resistance of soils.

The paper, which sets out the team's findings from observing and measuring the quality of these mineral bridges, paves the way for future developments in the field. Further tests, at different scales, are needed before the technology can be applied in the real world. The research was carried out under a 2018-2023 European Research Council (ERC) Advanced grant awarded to Prof. Lyesse Laloui, who heads the LMS and is a co-author of the paper. The project has three verticals, targeting the understanding of the fundamental mechanisms that occur at the soil-particle scale (micro-scale), the advanced characterization of mechanical behaviors at laboratory scale, and the large-scale development and demonstration of innovative systems in natural environments. In July 2020, the same research team obtained an additional ERC Proof of Concept grant to accelerate technology transfer to industrial applications.

In the past, soils were treated solely as a mix of solid earth, air and water. According to the co-authors, this research highlights how cross-disciplinary approaches - i.e., drawing on concepts from biology and electro-chemistry and incorporating advances and mechanisms from other scientific fields - can open exciting new paths and yield significant benefits.

An algal bloom refers to a phenomenon in which phytoplankton including blue-green algae rapidly proliferate in summer marked by high levels of solar irradiation and water temperature. It has lately been raising concerns due increased frequency of occurrence resulting from abnormally high temperatures and decreases in precipitation caused by climate change. There is a reason to be perturbed as certain species of blue-green algae produce substances that have an earthy or moldy taste and odor as well as toxic substances. Since these substances cannot be easily removed by a general water purification process, additional treatment using advanced water purification facilities and such is essential.

The Korea Institute of Science and Technology (KIST) revealed that a research team working under Dr. Kyung-Guen Song of the Water Cycle Research Center developed a purification process for effective treatment of taste- and odor-causing substances and toxic substances produced by blue-green algae even in the existing conventional drinking water treatment plants (DWTPs) without installing any additional advanced water treatment facilities.

In order to deal with algal blooms, large-scale DWTPs contain advanced water treatment facilities that use ozone and granular activated carbon, but in the case of conventional DWTPs without such advanced water treatment facilities, powdered activated carbon is added to adsorb algal micropollutants and chlorine treatment is reinforced as a way to increase the oxidizing strength. However, in the case of conventional powdered activated carbon, it is difficult to ensure sufficient contact time due to the slow adsorption of the algal micropollutants, thus requiring an injection of large amounts of powdered activated carbon to get the job done.

Dr. Song's team developed powdered activated carbon with an improved adsorption rate to better control algal blooms in the conventional DWTPs. The research team first pulverized powdered activated carbon to decrease the particle size. The powdered activated carbon with a reduced particle size was found to have a large number of fine pores on the surface, resulting in a larger area for adsorption of algal micropollutants. It was confirmed that the taste- and odor-causing substances and toxic substances produced by algae were adsorbed considerably faster (20% to 150% increase depending on the substance) compared to the conventional powdered activated carbon.

Dr. Song from KIST said, "Not only can the new powdered activated carbon be manufactured using quite a simple method, but it also has a fast adsorption rate, so it seems it will be possible to control algal blooms without the need to install high-cost facilities in existing conventional drinking water treatment plants where it is difficult to ensure sufficient contact time. Once this water treatment technology is disseminated widely, it will greatly help alleviate people's anxiety about drinking tap water."

Keeping players on the field and out of the courtroom is key for a team's success. A new study provides a possible pathway to reduce off-the-job player misconduct and it starts at the top. The researchers, Profs. Mary Graham and Bhavneet Walia from Syracuse University along with Chris Robinson from Tulane University, have concluded that teams which employ more women in executive level positions experience significantly fewer player arrests.

"Serious off-the-job misconduct by high-profile employees is not uncommon in professional sport team organizations, media and entertainment firms, and public-facing institutions, said Graham, Professor of Sport Management at Syracuse University's Falk College and lead author on the study. "Our research suggests that firms searching for preventive and remedial solutions to misconduct should consider a basic structural solution to this problem: ensuring that there is a critical mass of women on the top management team."

"Our findings also have implications for organizations beyond those employing professional sport players, particularly visible organizations with high-profile employees, such as media and entertainment companies; and public-facing entities such as courts, schools, and government entities," said Walia, an Assistant Professor of Public Health. "One of our goals was to shed light on organizational factors which might prevent, redress, or ameliorate instances of off-the-job misconduct by high-profile employees, including in the NFL."

Among the study's key findings:

Having a critical mass of women executives is associated with a reduction in player arrests of 21% for that team organization. Put differently, a critical mass of women executives (two or more) was associated with 0.33 fewer arrests.

The likelihood that a team, in any given season, experiences a player arrest is 15.4% lower for team organizations with a critical mass of women executives.

Also examined: the relationship between a critical mass of executives who are racial/ethnic minorities and player arrests. They found no relationship between having a critical mass of minority executives and player arrests." However, the authors speculate that the low numbers of minority executives might make it difficult to discern any effects.

"No studies have examined the relationship between gender diverse management teams and employee misconduct," said Robinson, a sports law attorney who is also a member of the research team. "We argue that the gender diversity of organizations' executive ranks has the potential to shape organization-level culture and norms of behavior that could influence employee conduct. Greater gender diversity also has the potential to shift strategic priorities and improve decision making."

Using new state-of-the-art imaging techniques to identify signs of osteoarthritis (OA), UniSA scientists are learning more about changes at the molecular level which indicate the severity of cartilage damage.

A study led by PhD student Olivia Lee and her supervisor Associate Professor Paul Anderson using mass spectrometry imaging (MSI) has mapped complex sugars on OA cartilage, showing different sugars are associated with damaged tissue compared to healthy tissue.

The finding will potentially help overcome one of the main challenges of osteoarthritis research - identifying why cartilage degrades at different rates in the body.

"Despite its prevalence in the community, there is a lot about osteoarthritis that we don't understand," Prof Anderson says.

"It is one of the most common degenerative joint diseases, yet there are limited diagnostic tools, few treatment options and no cure."

Existing OA biomarkers are still largely focused on bodily fluids which are neither reliable nor sensitive enough to map all the changes in cartilage damage.

By understanding the biomolecular structure at the tissue level and how the joint tissues interact in the early stages of osteoarthritis, UniSA researchers say any molecular changes could be targeted to help slow the progression of the disease with appropriate medication or treatment.

Osteoarthritis affects an estimated 2.2 million Australians and more than 300 million people worldwide, with those aged over 45 most at risk. Being female, overweight, and having existing joint injuries increases the risk of getting OA.

In Australia, $3.75 million is spent on joint replacements alone for osteoarthritis patients each year, and other indirect costs related to lost work productivity and loss of wellbeing are estimated to be more than $23 billion a year.

In a recent paper published in the International Journal of Molecular Sciences, Lee and her colleagues from UniSA's Musculoskeletal Biology Research Laboratory and the Future Industries Institute explore how advances in mass spectrometry imaging (MSI) to detect OA are promising.

"To date, diagnosing osteoarthritis has relied heavily on x-rays or MRI, but these provide limited information and don't detect biomolecular changes that signal cartilage and bone abnormalities," Lee says.

"By contrast, alternative imaging methods such as MSI can identify specific molecules and organic compounds in the tissue section."

MSI has already demonstrated its strengths in identifying biomarkers for different types of cancer, and UniSA researchers are hopeful it can achieve the same for early diagnosis of osteoarthritis.

Moore's law is an empirical suggestion describing that the number of transistors doubles every few years in integrated circuits (ICs). However, Moore's law has started to fail as transistors are now so small that the current silicon-based technologies are unable to offer further opportunities for shrinking.

One possibility of overcoming Moore's law is to resort to two-dimensional semiconductors. These two-dimensional materials are so thin that they can allow the propagation of free charge carriers, namely electrons and holes in transistors that carry the information, along an ultra-thin plane. This confinement of charge carriers can potentially allow the switching of the semiconductor very easily. It also allows directional pathways for the charge carriers to move without scattering and therefore leading to infinitely small resistance for the transistors. This means in theory the two-dimensional materials can result in transistors that do not waste energy during their on/off switching. Theoretically, they can switch very fast and also switch off to absolute zero resistance values during their non-operational states. Sounds ideal, but life is not ideal! In reality, there are still many technological barriers that should be surpassed for creating such perfect ultra-thin semiconductors. One of the barriers with the current technologies is that the deposited ultra-thin films are full of grain boundaries so that the charge carriers are bounced back from them and hence the resistive loss increases.

One of the most exciting ultra-thin semiconductors is molybdenum disulphide (MoS2) which has been the subject of investigation for the past two decades for its electronic properties. However, obtaining very large-scale two-dimensional MoS2 without any grain boundaries has been proven to be a real challenge. Using any current large-scale deposition technologies, grain-boundary-free MoS2 which is essential for making ICs has yet been reached with acceptable maturity. However, now researchers at the School of Chemical Engineering, University of New South Wales (UNSW) have developed a method to eliminate such grain boundaries based on a new deposition approach.

"This unique capability was achieved with the help of gallium metal in its liquid state. Gallium is an amazing metal with a low melting point of only 29.8 °C. It means that at a normal office temperature it is solid, while it turns into a liquid when placed at the palm of someone's hand. It is a melted metal, so its surface is atomically smooth. It is also a conventional metal which means that its surface provides a large number of free electrons for facilitating chemical reactions." Ms Yifang Wang, the first author of the paper said.

"By bringing the sources of molybdenum and sulphur near the surface of gallium liquid metal, we were able to realize chemical reactions that form the molybdenum sulphur bonds to establish the desired MoS2. The formed two-dimensional material is templated onto an atomically smooth surface of gallium, so it is naturally nucleated and grain boundary free. This means that by a second step annealing, we were able to obtain very large area MoS2 with no grain boundary. This is a very important step for scaling up this fascinating ultra-smooth semiconductor." Prof Kourosh Kalantar-Zadeh, the leading author of the work said.

The researchers at UNSW are now planning to expand their methods to creating other two-dimensional semiconductors and dielectric materials in order to create a number of materials that can be used as different parts of transistors.

A University of Waikato study has found that transgender people who have experienced stigma, including harassment, violence, and discrimination because of their identity are much more likely to have poor mental health outcomes.

Based on the responses of 1,178 people who completed a national Aotearoa/New Zealand survey, the findings published in the International Journal of Transgender Health, also show that over half (51%) of transgender people had been discriminated against for being transgender.

A team of experts from Waikato, and the University of Otago, assessed the results of the 2018 'Counting Ourselves' survey - a nationwide community-based questionnaire of transgender people living in Aotearoa/New Zealand.

Specifically, the team analysed the extent that stigma and discriminatory experiences alongside protective factors such as the support of friends, family, neighbours and communities, are related to the mental health of transgender people in Aotearoa/New Zealand.

Their results show that 23% of transgender people had been verbally harassed in public venues (such as public transport, retail stores and restaurants) for being transgender, whilst more than one-third (39%) had been victimised through cyberbullying.

It is well-documented that transgender people face high rates of discrimination, harassment, violence and serious mental health disparities.

Lead Author Kyle Tan says the findings of this research show that experiences of gender minority stress are strongly associated with mental health, including suicide, and that positive, protective factors appear to act as a buffer against this.

"One quarter (25%) of transgender participants who had high levels of discrimination, harassment and violence, and low levels of support from friends, family and community, had attempted suicide in the last year. However, only 3% of those who with low levels of discrimination, harassment, and violence and high levels of protective factors had attempted suicide. This means that those with lower risk factors and higher protective factors were more than eight times less likely to have attempted suicide."

Principal Investigator Dr Jaimie Veale added that these mental health inequities mean that transgender people should be a named priority in mental health and addiction policies.

"To improve the mental health and wellbeing of transgender people, we need to address the stigma and discrimination that they face. We also need to protect transgender people from violence, as a priority in sexual and domestic violence work."

** Reposted with permission of University of Waikato **

A new online game that puts players in the shoes of a purveyor of fake pandemic news is the latest tactic in efforts to tackle the deluge of coronavirus misinformation costing lives across the world.

The Go Viral! game has been developed by the University of Cambridge's Social Decision-Making Lab in collaboration with the UK Cabinet Office and media collective DROG.

It builds on research from Cambridge psychologists that found by giving people a taste of the techniques used to spread fake news on social media, it increases their ability to identify and disregard misinformation in the future.

Go Viral! is launched on the heels of a new study from the team behind it, just published in the Journal of Experimental Psychology: Applied. The latest findings show that a single play of a similar game can reduce susceptibility to false information for at least three months.

"Fake news can travel faster and lodge itself deeper than the truth," said Dr Sander van der Linden, who leads the project and the Social Decision-Making Lab at Cambridge.

"Fact-checking is vital, but it comes too late and lies have already spread like the virus. We are aiming to pre-emptively debunk, or pre-bunk, misinformation by exposing people to a mild dose of the methods used to disseminate fake news. It's what social psychologists call 'inoculation theory'."

The new 5-7 minute game introduces players to the basics of online manipulation in the era of coronavirus. It acts as a simple guide to common techniques: using emotionally charged language to stoke outrage and fear, deploying fake experts to sow doubt, and mining conspiracies for social media Likes.

"By using a simulated environment to show people how misinformation is produced, we can demystify it," said Dr Jon Roozenbeek, co-developer of Go Viral! and researcher at Cambridge's Department of Psychology. "The game empowers people with the tools they need to discern fact from fiction."

Go Viral! is based on a pre-COVID iteration, Bad News, which has been played over a million times since its 2018 launch. Cambridge researchers developed and tested Bad News, and found that just one play reduced perceived reliability of fake news by an average of 21% compared to a control group.

The research team, including DROG and designers Gusmanson (who also worked on Go Viral!), argue that this neutralising effect can contribute to a societal resistance to fake news when played by many thousands of people.

These initial results were confirmed in an even more rigorous replication study published in January this year. "Our pre-bunk game not only improved people's ability to spot fake news but also their confidence in judging what is true or false," said Melisa Basol, a Cambridge Gates Scholar who led the study.

"This confidence boost only occurred for those who got better at accurately identifying misinformation. By exposing people to the tactics behind fake news we can help create a general 'inoculation', rather than trying to counter each specific falsehood."

Intervention effects in social psychology often dissipate within days. However, the team's latest findings show that - when paired with added testing - the 'inoculation' of a single Bad News play lasts at least three months (the time limit of the study).

"We were very encouraged by the new results on longevity," said Rakoen Maertens, lead author and Cambridge PhD candidate. "In a society with ever-changing manipulation threats, the unique approach of interventions such as Bad News and Go Viral! can offer long-lasting effects not found when using a simple fact-check."

Go Viral! is a leaner, COVID-focused experience. The team used research on the current surge in coronavirus conspiracies - called an 'infodemic' by the WHO - to hone the game, creating a more direct version that is faster to complete and easier to adapt for different languages and cultures.

Recent research suggests that close to six thousand people around the world were hospitalised in just the first three months of this year due to coronavirus misinformation, with many dying after consuming cleaning products.

The game exposes the most pervasive 'infodemic' tactics. Players find out how real news gets discredited by exploiting fake doctors and remedies, and how false rumours such as the notorious 5G conspiracy get promoted.

It also touches on how out-of-context video gets used to add credibility to fake news - and ends with conspiracies slipping beyond your control, even seeping into the mainstream. Players are provided with a sharable score and connected to the WHO's COVID 'mythbusters'.

The Go Viral! project began with seed funding from Cambridge University's COVID-19 rapid response fund, and was then supported and backed by the UK Cabinet Office.

The collaboration is aiming to get out translations of the game right across the globe (the French and German translation are out now). The research team are working on further evidence-gathering through randomised experiments with national samples.

SAN FRANCISCO - Neoantigens, tiny markers that arise from cancer mutations, flag cells as cancerous and could be the key to unlocking a new generation of immunotherapies. Targeting the "right" neoantigens - in a cancer vaccine or a cell therapy - has the promise to eliminate a patient's cancer with minimal side effects. But hundreds of mutations can exist in a tumor, and only some can give rise to neoantigens that can trigger an immune response against cancer. The question is, which ones?

Scientists from an initiative launched by the Parker Institute for Cancer Immunotherapy (PICI) and the Cancer Research Institute called the Tumor Neoantigen Selection Alliance (TESLA) have discovered parameters to better predict which neoantigens can stimulate a cancer-killing effect. TESLA brings together a constellation of 36 top biotech, pharma, university and scientific nonprofit research teams. Their findings were published online today in Cell and could spawn a new generation of more effective, personalized cancer immunotherapies.

Through advanced computational analysis, the alliance discovered five characteristics that strongly indicated which cancer markers were most likely to generate an immune response. They fell into two major categories: the way the neoantigen is presented on the cancer cell and how the neoantigen is recognized by the immune system.

When the data model emphasizing these five characteristics was put to the test against another set of cancer samples, it accurately predicted 75 percent of effective neoantigen targets and filtered out 98 percent of ineffective ones.

"Our aim is that data produced from TESLA becomes the reference standard when developing a new neoantigen-based treatment," said Daniel Wells, Ph.D., principal data scientist at PICI and the study's corresponding author. "If every method, old and new, used the data to benchmark their predictions, the whole field would be able to collaborate and iterate on new methods much more quickly."

Wells co-led TESLA with Nadine Defranoux, Ph.D., a co-senior author on the paper.

To produce this benchmark, each TESLA team submitted its most promising neoantigen predictions for melanoma and non-small cell lung cancer (NSCLC) tissue to open science nonprofit Sage Bionetworks. PICI then cross-compared and validated which predictions were correct and recognizable by a T-cell.

When the five newly-found characteristics were reapplied to participating teams' algorithms, the predictions measurably improved.

"Until now, neoantigen prediction has been a black box. We had hints at what features might be important. The data model out of TESLA is the first to identify these five features as significant," said renowned neoantigen expert, co-senior author on the paper and professor Robert D. Schreiber, Ph.D., director of the Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs at Washington University School of Medicine in St. Louis.

Findings also demonstrated that no two prediction methodologies were alike, and most were significantly different. No team's methodology identified every neoantigen, nor a large majority of these cancer markers, indicating a need for a harmonized scientific effort like TESLA.

Further study is needed in other cancer types, but the discoveries are a significant step forward for neoantigen research.

"This research has the potential to improve drug makers' and researchers' mathematical algorithms. It can prioritize antigens most likely to be present on each patient's cancer and most visible to the immune system while deprioritizing the ones that aren't. That means better individualized treatments for patients," said Lisa Butterfield, Ph.D., vice president of research and development at PICI. "We're excited to see where the field takes these findings."

The full TESLA dataset, the largest of its kind, is available freely to the research community. The hope is that it can lead to accelerated personalized therapy development and even improved efficacy for cancer patients worldwide.

LEXINGTON, Ky. (Oct. 9, 2020) -- A new study is sounding the alarm on the impact climate change could have on one of the world's most vulnerable regions.

Michael McGlue, Pioneer Natural Resources Professor of Stratigraphy in the University of Kentucky Department of Earth and Environmental Sciences, and his team conducted the study at Lake Tanganyika -- a major African fishery. The results, which published today in Science Advances, show how certain changes in climate may place the fishery at risk, potentially diminishing food resources for millions of people in this area of eastern Africa.

"Lake Tanganyika's fish are a critically important resource for impoverished people from four nations (Tanzania, Democratic Republic of the Congo, Burundi and Zambia) and resilience to environmental change in that region is quite low," McGlue said. "Our study revealed that high frequency variability in climate can lead to major disruptions in how the lake's food web functions."

Small pelagic fish, known locally as dagaa, are abundant in Lake Tanganyika, and their conservation is pivotal to the food security and economy of rapidly growing and largely impoverished segments of these four nations.

Dagaa feed on algae and plankton, which means greater algae production in the lake results in more fish. How this aquatic food web responds to external forces, like climate, is critical for identifying vulnerabilities and maintaining healthy fish stocks. But until now, very limited information existed on how Lake Tanganyika may respond to such forces.

To understand how the lake reacts to climate changes, the team would need detailed information on the lake's upwelling -- the process by which deep waters rise and fertilize surface waters, thereby increasing algae and photosynthesis. In order to observe this, the team would have to obtain data from well-preserved sediment cores within the lake.

McGlue and his team traveled to one of the most remote regions of Lake Tanganyika, the southern basin, on a 12-day trip to collect these cores from the lake floor.

"The winds were especially violent that season, so most of our cruise was spent taking refuge from the waves in bays near the shoreline," McGlue said. "But in the narrow window when the winds dropped, we raced out to our stations and collected the cores."

McGlue and his team would later "read" the layers of sediment.

"The chemistry and fossil content of each layer tells us a specific story about how the lake functions," McGlue said. "Limnologists (scientists who study the lake today, like our co-author Dr. Ismael Kimirei) help us to translate the information in the sedimentary record and learn how climate change affects the lake's food web."

Until now, sedimentary records from Lake Tanganyika lacked the resolution needed to accurately measure the influence of frequent climatic events, such as the El Nino Southern Oscillation (ENSO). Most sedimentary datasets are low resolution, meaning that changes can only be detected over wide intervals of time, such as thousands of years. Conditions within certain areas of Lake Tanganyika converged to provide high temporal resolution of its sediment, which McGlue and his team were the first to sample.

"We were able to detect changes that were happening in Lake Tanganyika over very short intervals of time (e.g., months or years) using these sediments," McGlue said. "This is quite rare -- and crucial -- for using the data to guide fisheries management and conservation practices. Designing effective strategies for fisheries management using low resolution data is a challenge, because environmental changes that affect the food web can occur rapidly."

The team observed increases in algae production due to high solar irradiance -- the amount of energy from the sun that reaches Earth's atmosphere. According to the study, the convergence of high solar irradiance and La Nina results in a strong monsoon and upwelling, which increases algae in southern Lake Tanganyika. In contrast, a monsoon weakened by low solar irradiance and El Nino, as well as warmer surface waters, results in weak or absent upwelling and low algae production.

"(These samples provide) the detail that is necessary to capture abrupt change associated with teleconnective (climate) processes," said Jeffery Stone, co-author from Indiana State University.

The team says the socioeconomic threat these conditions create for sub-Saharan Africa is the most severe of any region on Earth, but they believe their findings can help guide long-term management practices.

"Armed with this knowledge, fisheries management strategies can be designed to help cope with these challenges," McGlue said.

Kimirei, who is also director-general of the Tanzania Fisheries Research Institute (TAFIRI), says the findings of this study are a critical building block toward research-informed policymaking in the Lake Tanganyika region.

"The importance of fisheries to the food security of the east and central African nations cannot be overemphasized," he said. "There is a growing body of research on declining fish production from Lake Tanganyika and other great lakes -- which coupled with the findings of this study, and the ever-increasing fishing pressure -- paint a gloomy future for the region. Therefore, sustainable fisheries of the lake can be achieved/maintained only if conventional fisheries management marries with ecosystem management and conservation approaches."

Co-author Sarah Ivory, with Penn State University, says the results make clear that changes in climate can have a cascading effect on the food webs in large tropical lakes.

"The impacts of this are akin to multi-year or multi-decade droughts in agricultural systems, from a food security perspective," she said.

Andrew Cohen, with the University of Arizona, says the findings have implications beyond tropical lakes as well.

"Climate impacts on freshwater resources in the tropics are a bellwether for global change worldwide," he said.

"This work is important, because climate changes that affect food security disproportionately hurt the poor," McGlue said. "This is one way science and social justice can become interwoven."

Abu Dhabi, UAE, October 9, 2020: The Plasmodium parasite, which transmits malaria to humans through infected mosquitos, triggers changes in human genes that alter the body's adaptive immune response to malarial infections, according to a team of researchers at NYU Abu Dhabi (NYUAD). The findings could bring hope for novel therapeutic strategies and a vaccine to the hundreds of thousands of people who die annually from malaria, a preventable and curable disease, and another three billion people who are at risk of infection.

The NYUAD researchers, in collaboration with the Centre National de Recherche et de Formation sur le Paludisme in Burkina Faso, NYUAD Assistant Professor of Biology Youssef Idaghdour, Associate Scientist Mame Massar Dieng, and Aïssatou Diawara, studied the blood of children in rural Burkina Faso, West Africa, and have discovered a new immune evasion strategy used by the Plasmodium parasite.

In the paper titled Integrative genomic analysis reveals mechanisms of immune evasion in P. falciparum malaria, published in the journal Nature Communications, the team of scientists studied the immune responses and genomes of the children before, during and after infection. They found that a class of genes, microRNAs (small molecules which play an integral role in regulation of genes involved in immune response) cause cell death of adaptive immune cells when in the presence of the Plasmodium parasite. Once the parasite avoids the immune response in the blood, it is then able to proliferate and invade other blood cells. It was also discovered that some microRNAs are under genetic control, which may explain why individuals and populations vary in their ability to cope with infection.

The largest burden of the disease occurs in Sub-Saharan Africa, where the negative socio-economic consequences are significant. The search for effective and sustainable therapeutic strategies for malaria has been stalled by a limited understanding of the sources of variation in host immune response to the parasitic infection.

"Our results shed new light on a mechanism for the weakening of adaptive immunity by invasive parasites," said Diawara. "This could explain why it takes years for children to develop immunity and why vaccines do not provide long-term protection," added Dieng.

"The next step for the team will be to perform more functional tests and to gain a better understanding of why certain groups of people in Africa are more immune to the disease than others," added Idaghdour. "Due to the impact of COVID-19 on healthcare systems, and screening and prevention programs, the burden of malaria could be worse in the coming years and it is our hope that this research can contribute to reaching the long-term goal of malaria elimination."

Palladium catalysts help synthesize key chemicals for many industries. However, direct reaction of two basic reagents, aryl halides and alkyllithium compounds, remains a challenge. Now, a team of scientists have found that a catalyst containing YPhos-type ligands can mediate this reaction even at room temperature. This discovery may contribute to the development of more sustainable processes in the chemical industry, the authors write in the journal Angewandte Chemie.

Palladium-catalyzed chemical processes are very useful. Palladium catalysts help to couple simple carbon-containing compounds to form more complicated chemical structures. However, they have yet failed to couple two common reagents in chemical synthesis, aryl halides and alkyllithium compounds. Among the aryl halides, aryl chlorides are common synthesis reagents that react variably during palladium-catalyzed reactions to produce side products.

For coupling reactions with aryl halides and alkyllithium compounds, chemists usually take "detours" by adding intermediate synthesis steps. Unfortunately, every extra synthesis step produces chemical waste and adds costs.

This problem led Viktoria Daeschlein-Gessner and her team from Ruhr University Bochum to investigate new palladium catalysts. They thought that a functional catalyst would ease many chemical syntheses. "The coupling of aryl chloride and alkyllithium reagents represents one of the most challenging reactions and--if being successful--promises a broad applicability," the authors explain.

After testing various existing catalysts, the authors identified a promising candidate. This catalyst was based on a class of ylide-substituted phosphines called YPhos.

Chemists use YPhos-containing palladium catalysts for difficult coupling reactions. The YPhos ligands combine a negatively charged carbon center and a positively charged phosphonium group (the ylide) with a phosphine-type ligand--phosphines are typical ligands in palladium catalysis. This ylide-phosphine ligand setup results in special electronic properties. The scientists observed that the ligand electronics helped to activate aryl halides, which is a crucial step in the reaction between aryl halides and alkyllithium compounds.

One of the YPhos class of ligands, a ligand called joYPhos, was shown to have the most favorable architecture. Its combination of electronic properties and a space-filling architecture suppressed the many side reactions otherwise occurring in the coupling.

The authors remark that precatalysts containing the YPhos ligands also performed extraordinarily well. Precatalysts have their ligands and a palladium source prearranged in separate compounds. Like two-component adhesives, they assemble in the reaction mixture to form the effective catalyst. This prearrangement makes their handling user-friendly and the compounds are more stable than the free ligands, according to the authors.

In a scale-up of the reaction, the scientists synthesized a building block of lesinurad, a drug used for treating gout. They also showed that the catalyst performed well for many variations of the aryl halide and alkyllithium reagents. These results led to the conclusion that this transformation is generally applicable. This new palladium catalyst may thus help to avoid costly "detours" in future organic syntheses.

Pioneering new research has helped geologists solve a long-standing puzzle that could help pinpoint new, untapped concentrations of some the most valuable rare earth deposits.

A team of geologists, led by Professor Frances Wall from the Camborne School of Mines, have discovered a new hypothesis to predict where rare earth elements neodymium and dysprosium could be found.

The elements are among the most sought after, because they are an essential part of digital and clean energy manufacturing, including magnets in large wind turbines and electric cars motors.

For the new research, scientists conducted a series of experiments that showed sodium and potassium - rather than chlorine or fluorine as previously thought - were the key ingredients for making these rare earth elements soluble.

This is crucial as it determines whether they crystalise - making them fit for extraction - or stayed dissolved in fluids.

The experiments could therefore allow geologists to make better predictions about where the best concentrations of neodymium and dysprosium are likely to be found.

The results are published in the journal, Science Advances on Friday, October 9th 2020.

University of Exeter researchers, through the 'SoS RARE' project, have previously studied many natural examples of the roots of very unusual extinct carbonatite volcanoes, where the world's best rare earth deposits occur, in order to try and identify potential deposits of the rare earth minerals.

However, in order to gain a greater insight into their results, they invited Michael Anenburg to join the team to carry out experiments at the Australian National University (ANU).

He simulated the crystallisation of molten carbonate magma to find out which elements would be concentrated in the hot waters left over from the crystallisation process.

It showed that sodium and potassium make the rare earths soluble in solution. Without sodium and potassium, rare earth minerals precipitate in the carbonatite itself. With sodium, intermediate minerals like burbankite form and are then replaced. With potassium, dysprosium is more soluble than neodymium and carried out to the surrounding rocks.

Professor Frances Wall, leader of the SoS RARE project said: "This is an elegant solution that helps us understand better where 'heavy' rare earths like dysprosium and 'light' rare earths like neodymium' may be concentrated in and around carbonatite intrusions. We were always looking for evidence of chloride-bearing solutions but failing to find it. These results give us new ideas."

Michael Anenburg , a Postdoctoral Fellow at ANU said: "My tiny experimental capsules revealed minerals that nature typically hides from us. It was a surprise how well they explain what we see in natural rocks and ore deposits."

A drug costing less than 2 euros per dose could reduce the long term consequences of a heart attack, benefitting millions of patients. Metoprolol, a member of the beta-blocker class of drugs that has been in use for more than 40 years, has been found to have unique cardioprotective properties.

This is the conclusion of a study carried out by scientists at the Centro Nacional de Investigaciones Cardiovasculares (CNIC), Fundación Jiménez Díaz University Hospital, and the Cardiovascular Disease Research Network (CIBERCV). The study, performed in sophisticated experimental mouse models, shows that the cardioprotective effect of metoprolol during a heart attack is not shared by other beta-blockers commonly administered by intravenous injection, such as atenolol and propranolol.

The European Heart Journal study [1] was led by Dr Borja Ibáñez, head of Clinical Research at the CNIC, a cardiologist at Fundación Jiménez Díaz University Hospital, and a CIBERCV group leader. The research "demonstrates that metoprolol has unique cardioprotective properties and heralds a paradigm change in cardiology and the treatment of acute myocardial infarction," said Dr Ibañez.

In 2013, the METOCARD-CNIC clinical trial, led and coordinated by the CNIC, showed that administration of metoprolol very early during an infarction limits damage to the heart and reduces long term consequences.

Four years later, in 2017, the same research team showed how and why this cheap and simple therapeutic strategy is so efficient. In a study published in Nature Communications, the researchers showed that the cardioprotective potential of metoprolol lies in its ability to block the action neutrophils--inflammatory cells activated during infection to eliminate pathogens--preventing them from entering the infarcted heart tissue.

Now, in 2020, the team has shown that metoprolol's cardioprotective properties are not shared by other beta-blockers and are thus not a class effect.

"The study presents important results that update and refine cardiovascular pharmacotherapy and underline how important it is not to assume that drugs in the same class will have identical activities and clinical indications," said pharmacist Agustín Clemente, a doctoral candidate at the CNIC and first author on the article.

Acute myocardial infarction is one of the main manifestations of cardiovascular disease and is the leading cause of death in the world. In Spain, more than 70 000 people have a heart attack every year. Current treatment guidelines recommend early administration of beta-blockers to patients with symptoms of an infarction but do not distinguish between the different drugs in this class. This is why the new results are so clinically significant.

Neutrophils, as well as protecting against infection, can become hyperactivated in other situations, such as during a myocardial infarction, when they can cause significant additional injury to the heart. Metoprolol is able to limit this hyperactivation, thereby preventing inflammatory damage associated with infarction.

The study also assessed the effects of different beta-blockers in other models of inflammatory disease, like lung damage and peritonitis. In all models examined, metoprolol was the only beta-blocker able to limit the organ damage inflicted by hyperactivated neutrophils. These findings could have an impact on the treatment of diseases in which injury is linked to neutrophil hyperactivation, including sepsis and possibly even COVID-19.

Building on the knowledge generated about metoprolol's cardioprotective effect, the research team used 3D intravital microscopy to investigate the effect of the drug on neutrophils. "This advanced imaging technology allowed us to study changes in cell movement and shape induced by metoprolol and to exclude a direct effect on these cells of other intravenous beta-blockers like atenolol or propranolol," explained Agustín Clemente.

Working with the CNIC Bioinformatics Unit, the research team conducted computational studies to assess the impact of different beta-blockers on type 1 beta adrenergic receptors, the molecular target of these drugs. "Unexpectedly, we found that despite their related chemical structures each drug interacts with beta-1 adrenergic receptors in a different way. This translates into a distinct structural change in the receptor for each drug, which in the case of metoprolol induces a specific molecular cascade and a concrete and unique cellular effect," commented co-principal investigator Dr Eduardo Oliver, a CNIC and CIBERCV pharmacologist and beneficiary of the Comunidad de Madrid talent program.

"Unlike other beta-blockers, metoprolol triggers a change in the intracellular structure of the beta-1 adrenergic receptor, opening it up so that it can interact with other nearby proteins that mediate the unique effect of metoprolol on neutrophil activity," added Dr Oliver.

Until now, beta-blockers were thought to act exclusively by impeding interaction between epinephrine and beta-1 adrenergic receptors. But the new results demonstrate that the binding of metoprolol not only blocks the action of epinephrine, but also activates other intracellular pathways, a phenomenon called biased agonism.

The authors conclude that metoprolol should be the beta-blocker of choice in clinical practice. "If these results are confirmed in future clinical studies, this would herald a change in the clinical guidelines for this devastating disease, placing metoproplol, and not other beta-blockers, as the drug of choice for patients suffering a heart attack," said Dr Ibañez.

The low cost of metoprolol, at less than 2 euros for an acute dose, brings additional value to this discovery.